Antibiotics

Clarithromycin Use and Risk of Death in Patients with Ischemic Heart Disease

2010-06-05T04:24:00.000-07:00

Clarithromycin Use and Risk of Death in Patients with Ischemic Heart Disease

Cardiology. 2010 Jun

Andersen SS, Hansen ML, Norgaard ML, Folke F, Fosbøl EL, Abildstrøm SZ, Raunsø J, Madsen M, Køber L, Gislason GH, Torp-Pedersen C.

Department of Cardiology, Gentofte Hospital, Copenhagen, Denmark.

Abstract

Objectives: To examine whether treatment with clarithromycin was associated with an increased risk of death in patients with preexisting ischemic heart disease (IHD).

Methods: Employing nationwide registers, all patients with IHD events from 1997 to 2007 who subsequently claimed prescriptions for dual antibiotic treatment for eradication treatment were identified. The primary endpoint was all-cause mortality.

Results: The study included 214,330 individuals with IHD; 5,265 (2.5 %) of these claimed prescriptions for dual antibiotics. Compared with IHD patients not undergoing eradication therapy, no increase in the risk of all-cause mortality was demonstrated (HR 1.02; 95% CI 0.84-1.23, p = 0.87) after 5 years. Conclusions: The use of clarithromycin in the setting of eradication treatment for Helicobacter pylori in patients with IHD was not associated with an increased risk of death.

Pubmed

Pediatric musculoskeletal infection: trends and antibiotic recommendations.

2009-10-17T06:34:00.000-07:00

Pediatric musculoskeletal infection: trends and antibiotic

recommendations

J Am Acad Orthop Surg. 2009 Oct

Copley LA.

Dr. Copley is Assistant Professor of Orthopaedic Surgery, Universityof Texas Southwestern, Dallas, TX.

Neither Dr. Copley nor a member of his immediate family hasreceived anything of value from or owns stock in a commercialcompany or institution directly or indirectly related to thesubject of this article.

In the past decade, the incidence of methicillin-resistant Staphylococcus aureus infections in children has increased. This phenomenon has led to a rise in complex, deep infections involving the musculoskeletal system for which a comprehensive approach of evaluation and treatment has become necessary. Whenever possible, cultures should be obtained to guide specific antibiotic selection. The potential for infections involving multiple tissue locations within the same patient and the risk for complications such as deep vein thrombosis necessitate a thorough, often multidisciplinary, approach in the care of these children. MRI is valuable in defining the anatomic and spatial extent of infection as well as in guiding the decision and approach for surgery. Most patients have favorable outcomes with sequential parenteral to oral antibiotic therapy after adequate surgical débridement of the infection. Close outpatient follow-up is essential to ensure antibiotic compliance and to identify late consequences of the infection.

American Academy of Orthopaedic Surgeons

Colistin: An overview

2009-10-12T05:29:00.000-07:00

Colistin / Hydrocortisone / Neomycin

Generic Name: Colistin/Hydrocortisone/Neomycin (koe-LIS-tin/hye-droe-KOR-ti-sone/nee-oh-MYE-sin)
Brand Name: Coly-Mycin S Otic

Colistin/Hydrocortisone/Neomycin is used for:

Treating infections of the ear caused by certain bacteria. It may also be used for other conditions as determined by your doctor.

Colistin/Hydrocortisone/Neomycin is a combination of 2 antibiotics and a corticosteroid. The antibiotics work by killing sensitive bacteria. The corticosteroid reduces inflammation.

Contraindications for use - Do Not Use

you are allergic to any ingredient in Colistin/Hydrocortisone/Neomycin , to other aminoglycosides (eg, gentamicin), or to other corticosteroids (eg, prednisone)
you have a viral infection of the ear (eg, herpes simplex, chickenpox, shingles)
you have a perforated ear drum

Contact your doctor or health care provider right away if any of these apply to you.

Before using Colistin/Hydrocortisone/Neomycin

Some medical conditions may interact with Colistin/Hydrocortisone/Neomycin . Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

if you are pregnant, planning to become pregnant, or are breast-feeding
if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement
if you have allergies to medicines, foods, or other substances
if you have the blood disease porphyria

Some MEDICINES MAY INTERACT with Colistin/Hydrocortisone/Neomycin . Because little, if any, of Colistin/Hydrocortisone/Neomycin is absorbed into the blood, the risk of it interacting with another medicine is low.

Ask your health care provider if Colistin/Hydrocortisone/Neomycin may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

Drugs.com

Colistin: An overview

INTRODUCTION

— Colistin (also called polymyxin E) belongs to the polymyxin group of antibiotics [1]. It was first isolated in Japan in 1949 from Bacillus polymyxa var. colistinus, and became available for clinical use in 1959 [2,3]. Colistin was given as an intramuscular injection for the treatment of Gram negative infections but fell out of favor after aminoglycosides became available because of its significant side effects. It was later used as topical therapy as part of selective digestive tract decontamination and is still used in aerosolized form for patients with cystic fibrosis.

More recently, a number of centers around the world have used colistin intravenously for otherwise panresistant nosocomial infections, especially those due to Pseudomonas and Acinetobacter spp [4-8].

The spectrum of activity, mechanisms of action and resistance, pharmacokinetics, interactions with other drugs, and adverse effects of colistin will be reviewed here. The clinical settings in which colistin may be used are discussed separately in the appropriate topic reviews.

MECHANISM OF ACTION

— Colistin is a bactericidal drug that binds to lipopolysaccharides and phospholipids in the outer cell membrane of gram-negative bacteria. It competitively displaces divalent cations from the phosphate groups of membrane lipids, which leads to disruption of the outer cell membrane, leakage of intracellular contents, and bacterial death [3,9,10].

In addition to its bactericidal effect, colistin can bind and neutralize lipopolysaccharide (LPS) and prevent the pathophysiologic effects of endotoxin in the circulation [11,12].

(Excerpt - UpToDate)

Colistin in the 21st century

2009-10-12T05:18:00.000-07:00

Colistin in the 21st century

Curr Opin Infect Dis. 2009 Sep 30

Nation RL, Li J.

Facility for Anti-infective Drug Development and Innovation, Drug Delivery, Disposition and Dynamics, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia.

PURPOSE OF REVIEW: Colistin is a 50-year-old antibiotic that is being used increasingly as a 'last-line' therapy to treat infections caused by multidrug-resistant Gram-negative bacteria, when essentially no other options are available. Despite its age, or because of its age, there has been a dearth of knowledge on its pharmacological and microbiological properties. This review focuses on recent studies aimed at optimizing the clinical use of this old antibiotic.

RECENT FINDINGS: A number of factors, including the diversity in the pharmaceutical products available, have hindered the optimal use of colistin. Recent advances in understanding of the pharmacokinetics and pharmacodynamics of colistin, and the emerging knowledge on the relationship between the pharmacokinetics and pharmacodynamics, provide a solid base for optimization of dosage regimens. The potential for nephrotoxicity has been a lingering concern, but recent studies provide useful new information on the incidence, severity and reversibility of this adverse effect. Recent approaches to the use of other antibiotics in combination with colistin hold promise for increased antibacterial efficacy with less potential for emergence of resistance.

SUMMARY:Because few, if any, new antibiotics with activity against multidrug-resistant Gram-negative bacteria will be available within the next several years, it is essential that colistin is used in ways that maximize its antibacterial efficacy and minimize toxicity and development of resistance. Recent developments have improved use of colistin in the 21st century.

Infectious Diseases

Update on antibiotics for infection control in cystic fibrosis.

2009-10-11T08:57:00.000-07:00

Update on antibiotics for infection control in

cystic fibrosis.

Expert Rev Anti Infect Ther. 2009 Oct

Kirkby S, Novak K, McCoy K.

Section of Pulmonary Medicine, Nationwide Children's Hospital, Ohio State University Medical Center, Columbus, OH 43205, USA. stephen.kirkby@nationwidechildrens.org

Cystic fibrosis pulmonary disease is characterized by chronic and recurrent infection, airway inflammation, bronchiectasis and progressive obstructive lung physiology. Advances in the treatment of common airway pathogens such as Pseudomonas aeruginosa have led to a marked improvement in overall survival. However, antibiotic treatment options are often limited by multidrug resistance, potential toxicities and treatment burden to individual patients. While appropriate anti-infective therapy reduces bacterial density in the airways and may result in clinical improvement, true eradication of airway infection is seldom achieved except for early-stage infections. This review summarizes current approaches for acute and chronic anti-infective therapy in cystic fibrosis.

Expert Reviews

Role of old antibiotics in multidrug resistant bacterial infections.

2009-10-11T08:37:00.000-07:00

Role of old antibiotics in multi-drug resistant bacterial infections.

Curr Drug Targets. 2009 Sep

Maviglia R, Nestorini R, Pennisi M.

Department of Emergency Care, Catholic University, Roma, Italy. r.maviglia@mclink.it

Multidrug resistant bacteria infections are associated with an increase in attributable mortality and morbidity in ICU patients. Unfortunately, an emerging resistance to novel antibiotics used in the therapy of gram negative and gram positive bacteria infections is often reported in literature. Old antibiotics have been reintroduced in clinical practice. In this review we report the efficacy and safety use of older antimicrobial agents in critically ill patients. Polymyxins are used for nosocomial infection caused by Pseudomonas aeruginosa and Acinetobacter baumannii resistant strains. Patients with polymyxin-only susceptible gram-negative nosocomial pneumonia are reported to be successfully treated with inhaled colistin. Isepamicin can probably be used in intensive care units that harbor Gram-negative bacteria resistant to other aminoglycosides. Fosfomycin may be a useful alternative to linezolid and quinupristin-dalfopristin in the treatment of Vancomycin Resistant Enterococci (VRE) infections in certain clinical situations, e.g. uncomplicated urinary tract infections. Chloramphenicol has a wide antimicrobial spectrum and excellent tissue penetration; though it is sometimes used empirically in the hospital setting for the treatment of patients with unknown source of fever, its role is still a matter of controversy. The colistin/rifampicin combination might have a synergistic effect in Acinetobacter baumannii and Pseudomonas aeruginosa infections. Fusidic acid is active against staphylococcal strains.

PubMed

Efficacy and Safety of Sequential Intravenous/Oral Moxifloxacin vs Intravenous/Oral Amoxicillin/Clavulanate for Complicated Skin, Structure Infections

2009-09-29T04:26:00.000-07:00

Efficacy and Safety of Sequential Intravenous/Oral

Moxifloxacin vs Intravenous/Oral Amoxicillin/Clavulanate

for Complicated Skin, Structure Infections

R. Vick-Fragoso¹, G. Hernández-Oliva², J. Cruz-Alcázar², C. F. Amábile-Cuevas³, P. Arvis⁴, P. Reimnitz⁵, J. R. Bogner⁶ and The STIC Study Group

(1)	Infectious Disease Dept., Hospital General “Dr Manuel Gea González”, Calzada de Tlalpan, Tlalpan, Mexico, D.F., Mexico

(2)	Hospital de Infectología, Centro Médico Nacional “La Raza”/Bayer de México, Mexico City, Mexico

(3)	Fundación Lusara, Mexico City, Mexico

(4)	Division Bayer Schering Pharma, Bayer Santé, Loos Cedex, France

(5)	Bayer Vital GmbH, Building 431, BHC-BSP GCD-GB-GCS-CSE II, Wuppertal, Germany

(6)	Dept. for Infectious Diseases, University Hospital of Munich, Downtown Campus, Pettenkoferstrasse 8a, 80336 Munich, Germany

Received: 11 December 2008 Accepted: 15 July 2009 Published online: 18 September 2009

Vick-Fragoso R, Hernández-Oliva G, Cruz-Alcázar J, Amábile-Cuevas CF, Arvis P, Reimnitz P, Bogner JR; The STIC Study Group.

Infectious Disease Dept., Hospital General "Dr Manuel Gea González", Calzada de Tlalpan, Tlalpan, Mexico, D.F., Mexico.

BACKGROUND: Complicated skin and skin structure infections (cSSSIs) are an important healthcare concern worldwide, as they can be life-threatening and challenging to treat. cSSSIs are normally managed using a combination of surgical intervention and prompt antibiotic use. New therapeutic options, including novel antibiotics, are required to improve outcomes in terms of duration of illness and to reduce the consumption of healthcare resources.

METHODS: This was a prospective, randomized, open-label, parallel-group, multinational clinical study comparing sequential intravenous/oral (iv/po) moxifloxacin, 400 mg once daily, and iv amoxicillin/clavulanate, 1,000 mg/200 mg three times daily followed by po amoxicillin/clavulanate, 500 mg/125 mg three times daily, for 7-21 days in hospitalized patients.

RESULTS: A total of 804 patients were enrolled (mean age 51.8 years). The most common clinical diagnosis was complicated erysipelas (32.1% moxifloxacin; 30.0% amoxicillin/clavulanate) and major abscess (31.1% moxifloxacin; 29.3% amoxicillin/clavulanate). Overall clinical success rates at the test-of-cure (TOC) visit (14-28 days post-treatment) for the per-protocol population (primary efficacy variable) were 80.6% (254/315) for patients in the moxifloxacin group and 84.5% (268/317) for those receiving amoxicillin/clavulanate (95% confidence interval [CI] -9.41, 2.18). Similar results were obtained for the intention-to-treat population (95% CI -7.56, 4.31). In both treatment groups, the highest clinical success rates were recorded for patients with complicated erysipelas, major abscess, surgical wound infection, and cellulitis. The lowest clinical cure rates were reported for diabetic foot infection and necrotizing fasciitis. In the microbiologically evaluable population, the bacteriological success rate (eradication and presumed eradication) was 76.0% (127/167) in the moxifloxacin group and 81.4% (140/172) in the amoxicillin/clavulanate group (95% CI -12.96, 4.41). Staphylococcus aureus (137 isolates) and Escherichia coli (50 isolates) were the most frequently isolated skin pathogens. Adverse event rates were comparable between treatment groups.

CONCLUSIONS: Treatment with sequential iv/po moxifloxacin monotherapy once daily is clinically comparable to that with iv/po amoxicillin/clavulanate three times daily in the management of cSSSIs. Moxifloxacin's simple dose regimen offers an advantage over amoxicillin/clavulanate and represents a valuable addition to current antibiotic regimens used in the treatment of cSSSIs.

Sringerlink

Retapamulin: a review of its use in the management of impetigo and other uncomplicated superficial skin infections.

2009-09-29T04:04:00.000-07:00

Retapamulin: a review of its use in the management

of impetigo

and other uncomplicated superficial skin infections

Drug Ther Bull. 2008 Oct

Last year, we concluded that topical fusidic acid should be first-line treatment for impetigo. Since then, retapamulin ointment (Altargo - GlaxoSmithKline), a new antibacterial, has been licensed in the European Union as a short-term treatment for impetigo and infected small lacerations, abrasions or sutured wounds in people aged 9 months or above. Advertisements claim that the product "treats localised impetigo in just 5 days"; by comparison, the British National Formulary (BNF) advises a 7-day course of fusidic acid. Here we consider the place of retapamulin in impetigo and its other licensed indications.

PubMed/BMJ

Assessment of antibiotic resistance in probiotic strain Lactobacillus brevis KB290.

2009-09-28T04:05:00.000-07:00

Assessment of antibiotic resistance in probiotic strain Lactobacillus brevis KB290.

J Food Prot. 2009 Sep

Fukao M, Tomita H, Yakabe T, Nomura T, Ike Y, Yajima N.

Probiotics Research Department, Research Institute, Kagome Company, Limited, 17 Nishitomiyama, Nasushiobara, Tochigi, 329-2762, Japan. Masanori_Fukao@kagome.co.jp

Our purpose was to investigate the safety of the probiotic strain Lactobacillus brevis KB290. The European Qualified Presumption of Safety (QPS) evaluation approach was applied to the strain. We determined the strain's antibiotic resistance, verified it at the genetic level, and determined whether it could be transferred to intestinal microflora. Of 14 antibiotics tested, 11 showed MICs within the limits of the QPS criteria. However, the L. brevis KB290 MICs of ciprofloxacin (a fluoroquinolone), tetracycline, and vancomycin were two, four, and eight times, respectively, the breakpoint MICs suggested by the European Scientific Committee on Animal Nutrition, and the MIC of tetracycline was eight times the breakpoint MIC suggested by the European Scientific Panel on Additives and Products or Substances Used in Animal Feed. Using analysis of gapped-genome sequences, we found no known transferable determinants for tetracycline or vancomycin resistance, and we found no mutations in the quinolone resistance-determining regions of the genes encoding GyrA or ParC for ciprofloxacin resistance associated with insertion sequences, integrons, or transposons. These data were confirmed by using PCR primers specific for the respective genes. We assessed the transferability of the resistance traits in conjugation experiments with enterococci and obtained no transconjugants, strongly suggesting that the resistance traits were not transferable. This study demonstrated that the antibiotic resistance observed in L. brevis KB290 was due not to dedicated mechanisms but to intrinsic resistance. According to the QPS criteria, these results provide safety assurance for the ongoing use of L. brevis KB290 as a probiotic.

PMID: 19777895 [PubMed - in process]

The Use of New and Better Antibiotics for Bacterial Infections in Patients With Leukemia.

2009-09-28T04:01:00.000-07:00

The Use of New and Better Antibiotics for Bacterial Infections in Patients With Leukemia.

Clin Lymphoma Myeloma. 2009 Sep

Rolston KV.

Department of Infectious Diseases, Infection Control and Employee Health, The University of Texas M. D. Anderson Cancer Center, Houston.

Bacterial infection is the most common complication of chemotherapy-induced neutropenia particularly in patients with hematologic malignancies. Bacterial infections predominate during the initial phases of neutropenic episodes. The spectrum of bacterial infection continues to evolve globally and locally at the institutional level, as do patterns of antimicrobial susceptibility/resistance. These trends are often associated with local treatment practices (eg, use of antimicrobial prophylaxis, open versus restricted formularies, clinical pathways and/or guidelines) and have a significant effect on the nature of empiric antimicrobial therapy. Increasing rates of resistance among gram-positive and gram-negative bacteria are posing new therapeutic challenges. These challenges can to some extent be overcome by new drug development. Many novel agents for the treatment of resistant gram-positive infections have been developed and are being evaluated in clinical trials. Newer agents for the treatment of Clostridium difficile associated diarrhea are also in the pipeline. Far fewer options to treat multi-drug resistant gram-negative infections exist, and new drug development is lagging behind. Consequently, the judicious use of currently available agents is essential. This is best achieved by the development of multidisciplinary antibiotic stewardship teams that gather baseline data, make recommendations for appropriate antimicrobial usage, and provide monitoring and feedback services to clinical care providers. Along with strict adherence to infection control policies, antimicrobial stewardship provides the best strategies for the management of infectious complications in patients with hematologic malignancies and other high-risk settings.

PubMed

Comparative antibacterial effects of daptomycin, vancomycin and teicoplanin studied in an in vitro pharmacokinetic model of infection.

2009-09-21T22:24:00.000-07:00

Comparative antibacterial effects of daptomycin, vancomycin and teicoplanin studied in an in vitro pharmacokinetic model of infection
J Antimicrob Chemother. 2009 Sep 16

Bowker KE, Noel AR, Macgowan AP.
Bristol Centre for Antimicrobial Research and Evaluation (BCARE), Department of Microbiology, Southmead Hospital, Westbury-on-Trym, Bristol BS10 5NB, UK.

* Corresponding author. Tel: +44-(0)1179-9595654; Fax: +44-(0)117-9593217; E-mail: karen.bowker@nbt.nhs.uk

Objectives
To compare the antibacterial effects (ABEs) of the free (f) drugs daptomycin, vancomycin and teicoplanin against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant S. aureus (VRSA), using high and low inocula in a pharmacokinetic in vitro model. To determine the daptomycin fAUC/MIC ratio for a static effect and 3 log reduction in viable count and relate this target to the clinical breakpoint.

Methods
Five clinical MRSA isolates held at Southmead Hospital were used (SMH 15841, SMH 40289, SMH 40275, SMH 33922 and SMH 33024) together with a VRSA isolate (SMH 19898); inocula of 10(6) and 10(8) cfu/mL were used. Daptomycin (6 mg/kg once daily), vancomycin (1 g twice daily) and teicoplanin (400 mg once daily) regimens were simulated. ABEs were measured using the 24 h area-under-the-bacterial kill curve (AUBKC) and log change in viable count at 24 h (Delta24). For daptomycin, dose escalation was used to determine the relationship between ABE and AUC/MIC.

Results
Daptomycin was bactericidal against the MRSA strains. Daptomycin and vancomycin were active against the VRSA strain; teicoplanin had a static effect. The higher inoculum reduced the ABEs. Analysis of variance (ANOVA) indicated that daptomycin had a superior ABE to teicoplanin and vancomycin. Daptomycin fAUC/MIC was related to AUBKC and Delta24; the fAUC/MIC ratios for a static effect and 1 log and 3 log drop were 37.2 +/- 16.5, 40.6 +/- 17.8 and 49.8 +/- 19.2, respectively.

Conclusions
These data define the fAUC/MIC sizes for daptomycin for bacteriostatic and bactericidal ABEs and indicate that a 6 mg/kg dose of daptomycin is superior to vancomycin and teicoplanin against MRSA and VRSA strains.

Antimicrobial Chemotherapy

Rational antibiotic use.

2009-09-20T12:15:00.000-07:00

Rational antibiotic use.

J Infect Dev Ctries. 2009 Mar

Tunger O, Karakaya Y, Cetin CB, Dinc G, Borand H.
Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Celal Bayar University, Manisa, Turkey. otunger@hotmail.com

BACKGROUND: Development of resistance to antimicrobial agents and increase of cost as the result of unnecessary and inappropriate use of antibiotics has become a global health problem. Therefore many strategies, which are aimed at optimizing antibiotic therapy, have been developed until now. In Turkey, an antibiotic restriction policy as a governmental solution was applied to decrease the antibiotic use and especially costs by Ministry of Health in 2003. The aim of this study is to evaluate the rational antibiotic use and the impact of the implementation of new restriction policy, with their reinforcement by infectious disease specialist, on the hospital wide use of antibiotics.

METHODOLOGY: The data of the inpatients received antibiotics (n=495) during January-June 2006 were compared with our previous study performed by the same methodology before the restriction policy in 1998. In both studies, prospective active daily surveillance of patients was performed by three infectious disease specialists. The appropriateness of antibiotic therapy was determined using the criteria described by Kunin and Jones. The data were analyzed by using SPSS for Windows.

RESULTS: Thirty-seven patients were treated for burn cellulitis, 26 (70%) of whom were treated initially with continuous-infusion oxacillin. Other initial antibiotics were chosen because of concomitant infections, penicillin allergy, or development of cellulitis during treatment with a beta-lactam antibiotic. Oxacillin treatment was successful in 19 patients (73%). Success required an average of 5.16 days, with 1.53 days required for fever resolution and 0.89 days for resolution of leukocytosis. Seven patients who did not respond rapidly were switched to intravenous vancomycin an average of 2.4 days after starting oxacillin, leading to a 100% success rate. There were no deaths, and only one suspected case of allergic reaction to oxacillin. In eleven patients treated with other antibiotics, the success rate was 75%. Success with these drugs required a longer treatment course of 6.45 days. Leukocytosis resolved significantly more slowly at 4.45 days -p equals 0.02-, and fever resolution was also slower at 3.18 days.

CONCLUSIONS: Continuous-infusion oxacillin was successful in the treatment of 73% of patients, a success rate that might have been higher with clinical patience, and leukocytosis resolved faster than with other antibiotics. Failure of continuous-infusion oxacillin can be managed without clinical consequence by conversion to intravenous vancomycin.

PubMed

Antibacterial activity and cytotoxicity of PEGylated poly(amidoamine) dendrimers

2009-09-17T06:55:00.000-07:00

Antibacterial activity and cytotoxicity of PEGylated poly(amidoamine) dendrimers

Mol Biosyst. 2009 Oct;
Lopez AI, Reins RY, McDermott AM, Trautner BW, Cai C.
Department of Chemistry, University of Houston, Houston, TX, USA. cai@uh.edu.

We have investigated the antibacterial activity and cytotoxicity of a series of amino-terminated poly(amidoamine) (PAMAM) dendrimers modified with poly(ethylene glycol) (PEG) groups. The antibacterial activity of the PAMAM dendrimers and their derivatives against the common ocular pathogens, Pseudomonas aeruginosa and Staphylococcus aureus, was evaluated by their minimum inhibitory concentrations (MICs). For the unmodified third and fifth generation (G3 and G5) amino-terminated dendrimers, the MICs against both P. aeruginosa and S. aureus were in the range of 6.3-12.5 mug mL(-1), comparable to that of the antimicrobial peptide LL-37 (1.3-12.5 mug mL(-1)) and within the wide range of 0.047-128 mug mL(-1) for the fluoroquinolone antibiotics. PEGylation of the dendrimers decreased their antibacterial activities, especially for the Gram-positive bacteria (S. aureus). The reduction in potency is likely due to the decrease in the number of protonated amino groups and shielding of the positive charges by the PEG chains, thus decreasing the electrostatic interactions of the dendrimers with the negatively-charged bacterial surface. Interestingly, localization of a greater number of amino groups on G5 vs. G3 dendrimers did not improve the potency. Significantly, even a low degree of PEGylation, e.g. 6% with EG(11) on G3 dendrimer, greatly reduced the cytotoxicity towards human corneal epithelial cells while maintaining a high potency against P. aeruginosa. The cytotoxicity of the PEGylated dendrimers to host cells is much lower than that reported for antimicrobial peptides. Furthermore, the MICs of these dendrimers against P. aeruginosa are more than two orders of magnitude lower than other antimicrobial polymers reported to date. These results motivate further exploration of the potential of cationic dendrimers as a new class of antimicrobial agents that may be less likely to induce bacterial resistance than standard antibiotics.

PubMed

Antibiotic therapy in small intestinal bacterial overgrowth: rifaximin versus metronidazole

2009-06-11T08:12:00.000-07:00

Antibiotic therapy in small intestinal bacterial overgrowth: rifaximin versus metronidazole
Eur Rev Med Pharmacol Sci. 2009 Mar-Apr

Lauritano EC, Gabrielli M, Scarpellini E, Ojetti V, Roccarina D, Villita A, Fiore E, Flore R, Santoliquido A, Tondi P, Gasbarrini G, Ghirlanda G, Gasbarrini A.
Internal Medicine Department, Catholic University of the Sacred Heart, Rome, Italy.

BACKGROUND AND OBJECTIVES: Few controlled trials on antibiotic therapy for small intestinal bacterial overgrowth are available at present. Aim of the study was to assess efficacy, safety and tolerability of rifaximin with respect to metronidazole for the treatment of small intestinal bacterial overgrowth.

MATERIAL AND METHODS: We enrolled 142 consecutive patients with diagnosis of small intestinal bacterial overgrowth. Diagnosis of small intestinal bacterial overgrowth based on the clinical history and the positivity of glucose breath test. Patients were randomised to two 7-day treatment groups: rifaximin 1200 mg/day and metronidazole 750 mg/day. Glucose breath test was reassessed 1 month after. Compliance and side-effect incidence were also evaluated.

RESULTS: One drop-out was observed in rifaximin group. Five drops-out occurred in metronidazole group. The glucose breath test normalization rate was significantly higher in the rifaximin with respect to the metronidazole group (63.4% versus 43.7%; p <>

DISCUSSION: Rifaximin showed an higher SIBO decontamination rate than metronidazole at the tested doses, both with a significant gain in terms of tolerability. Either the present study or recent evidencies suggest that rifaximin represents a good choice for the management of patients affected by SIBO.

PubMed

Aerosol antibiotic therapy in children with chronic upper airway infections: a potential alternative to surgery

2009-06-11T08:08:00.000-07:00

Aerosol antibiotic therapy in children with chronic upper airway infections: a potential alternative to surgery

Int J Immunopathol Pharmacol. 2009 April-June

Macchi A, Castelnuovo P.
Department of Otorhinolaryngology University of Insubria, Varese, Azienda Ospedaliero Universitaria Ospedale di Circolo e Fondazione Macchi, Varese, Italy.

Tonsillectomy and adenoidectomy remain the first choice treatment of chronic or recurrent acute infections of the upper respiratory tract in children. The aim of this study is to investigate the efficacy of the combination of thiamphenicol glycinate acetylcysteinate plus beclomethasone, administered as aerosol, in children awaiting tonsillectomy and/or adenoidectomy. The study comprised 204 children, aged 1 to 12 years, with chronic adenotonsillitis who had been listed for surgery due to obstructive symptoms and recurrent acute infections. Patients were randomized to treatment with thiamphenicol glycinate acetylcysteinate, dosage 250 mg/day in 2 administrations plus beclomethasone with a dosage of 400 μg/day in 2 administrations, or no treatment, control group, unless required. The drugs were administered by aerosol for 10 days/month over a period of 6 months. Clinical visits were at 4, 7 and 12 months after the start of treatment. The primary efficacy outcome was the reduction in the number of patients requiring surgery. Secondary efficacy measures were the reduction of nasal obstruction, the decrease in the number of infectious episodes and the tolerability of the treatment. Aerosol treatment with thiamphenicol glycinate acetylcysteinate plus beclomethasone resulted in a significantly lower proportion of patients requiring surgery (29 of 101; 29 percent) compared to patients in the control group (100 of 103; 97 percent) (p < 0.0001). Treatment was also associated with a reduction of nasal obstruction and a decrease in the number of infectious episodes. No treatment-related adverse events were reported and the aerosol therapy proved easy to administer to children. The aerosol therapy with the combination of thiamphenicol glycinate acetylcysteinate plus beclomethasone was able to prevent or postpone surgery in a substantial percentage of patients, without adverse events. These preliminary results suggest that this novel approach could play a role in the antibiotic prophylaxis of chronic infectious diseases of the upper airways.

PubMed

Current topical and systemic approaches to treatment of rosacea

2009-06-11T07:57:00.000-07:00

Current topical and systemic approaches to treatment of rosacea
J Eur Acad Dermatol Venereol. 2009 Jun

Korting H, Schöllmann C.
Department of Dermatology and Allergology, Ludwig-Maximilians-Universität, Munich, Germany.

Rosacea is a common, often overlooked, chronic facial dermatosis characterized by intermittent periods of exacerbation and remission. Clinical subtypes and grading of the disease have been defined in the literature. On the basis of a genetic predisposition, there are several intrinsic and extrinsic factors possibly correlating with the phenotypic expression of the disease. Although rosacea cannot be cured, there are several recommended treatment strategies appropriate to control the corresponding symptoms/signs. In addition to adequate skin care, these include topical and systemic medications particularly suitable for the papulopustular subtype of rosacea with moderate to severe intensity. The most commonly used and most established therapeutic regimens are topical metronidazole and topical azelaic acid as well as oral doxycycline.

Conventionally, 100-200 mg per day have been used. Today also a controlled release formulation is available, delivering 40 mg per day using non-antibiotic, anti-inflammatory activities of the drug. Anti-inflammatory dose doxycycline in particular allows for a safe and effective short- and long-term therapy of rosacea. Topical metronidazole and topical azelaic acid also appear to be safe and effective for short-term use. There are indications that a combined therapy of anti-inflammatory dose doxycycline and topical metronidazole could possibly have synergy effects. Further interesting therapy options for the short- and long-term therapy of rosacea could be low-dose minocycline and isotretinoin; however, too little data are available with regard to the effectiveness, safety, optimal dosage and appropriate length of treatment for these medications to draw final conclusions.

PubMed

Antibiotics and probiotics in inflammatory bowel disease: why, when, and how

2009-05-19T07:14:00.000-07:00

Antibiotics and probiotics in inflammatory bowel disease: why, when, and how
Curr Opin Gastroenterol. 2009 May 11

Prantera C, Scribano ML.
Azienda Ospedaliera San Camillo-Forlanini, Rome, Italy.

PURPOSE OF REVIEW: To summarize recent evidence on the role of intestinal bacteria in inflammatory bowel diseases, and of antibiotics and probiotics in their treatment. The implications connected with the use of antibiotics are also examined.

RECENT FINDINGS: The hypothesis that Mycobacterium paratuberculosis could be a causative agent of Crohn's disease has not been confirmed by a large trial on symptomatic patients treated by a combination of antibiotics active against this bacterium. An increased number of adherent-invasive Escherichia coli have been found in the intestinal tissue of patients with Crohn's disease, but their role in the pathogenesis of this condition remains to be defined. The combination of metronidazole and azathioprine, associating the effects of a reduced bacterial load with immunosuppression, appears to be a therapeutic option to decrease the recurrence of postoperative Crohn's disease in high-risk patients. However, concerns are raised by the possibility that antibiotics may induce disease relapse due to Clostridium difficile infection.

SUMMARY: Recent literature provides increasing support for the use of antibiotics in Crohn's disease, although the side effects limit their long-term use. The efficacy of antibiotics in ulcerative colitis is not confirmed by the available literature, except in severe colitis. More trials are needed to support the use of probiotics as therapy in inflammatory bowel disease.

PMID: 19444096 [PubMed - as supplied by publisher]

Antibiotic Use in Premature Infants After Discharge From the Neonatal Intensive Care Unit.

2009-05-19T07:10:00.000-07:00

Antibiotic Use in Premature Infants After Discharge From the Neonatal Intensive Care Unit.
Clin Pediatr (Phila). 2009 May 15

Lorch SA, Wade KC, Bakewell-Sachs S, Medoff-Cooper B, Silber JH, Escobar GJ.

Using a retrospective cohort of premature infants, we constructed multivariable Poisson models to determine factors associated with the receipt of antibiotics during the first year after discharge, N = 891. Black race (incidence rate ratio 1.80 compared with White infants, P = .008), male gender (incidence rate ratio 1.44; P = .007), bronchopulmonary dysplasia (incidence rate ratio 1.47; P = .04), and each additional child at home (incidence rate ratio 1.21, P = .002) increased the receipt of antibiotics for any reason. Male gender and additional children at home increased the receipt of nonrecommended antibiotics, while Black infants received care at facilities that prescribed more nonrecommended antibiotics. Even in a high-risk population of children, factors other than the medical history and presentation of the child may alter antibiotic prescription patterns and result in variations in care.

PMID: 19448131 [PubMed - as supplied by publiusher]

Antimicrobial and antibiofilm efficacy of triclosan and DispersinB(R) combination

2009-05-19T07:05:00.000-07:00

Antimicrobial and antibiofilm efficacy of triclosan and DispersinB(R) combination
Antimicrob Chemother. 2009 May 14

Darouiche RO, Mansouri MD, Gawande PV, Madhyastha S.
Center for Prostheses Infections and Infectious Disease Section, Michael E. Debakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, TX, USA.

Objectives: The objectives of this study were to examine: (i) synergy of the combination of triclosan and DispersinB((R)) (DspB); (ii) in vitro efficacy and durability of triclosan + DspB-coated vascular catheters; and (iii) in vivo efficacy of triclosan + DspB-coated catheters compared with chlorhexidine-silver sulfadiazine (CH-SS)-coated and uncoated (control) vascular catheters in preventing colonization by Staphylococcus aureus.

Methods: We investigated the potential synergistic antimicrobial and antibiofilm activity of triclosan and DspB by biofilm assays. The in vitro antimicrobial efficacy of triclosan + DspB-coated catheters was determined by microbial colonization assays. Antimicrobial durability of the coated catheters was tested by soaking segments in bovine serum for 7 days and determining antimicrobial activity, and by a serial plate transfer method. The in vivo efficacy of triclosan + DspB-coated catheters compared with CH-SS-coated and uncoated catheters was assessed by subcutaneous implantation of segments in a rabbit model of S. aureus infection.

Results: The combination of triclosan and DspB showed synergistic antimicrobial and antibiofilm activity against S. aureus, Staphylococcus epidermidis and Escherichia coli, significantly reduced bacterial colonization (P less then 0.05) and generally demonstrated a prolonged superior antimicrobial activity against clinical pathogens compared with CH-SS-coated catheters. Triclosan + DspB-coated and CH-SS-coated catheters exhibited equal in vivo efficacy (P less then/= 0.05) in reducing colonization by S. aureus compared with uncoated catheters.

Conclusions: Catheters coated with the triclosan + DspB combination showed synergistic, broad-spectrum and durable antimicrobial activity. Furthermore, the in vivo efficacy of catheters coated with this unique antimicrobial/antibiofilm composition prompts clinical evaluation of such an innovative approach.

PMID: 19447791 [PubMed - as supplied by publisher]

Maintaining a Sterile Urinary Tract: The Role of Antimicrobial Peptides

2009-05-19T07:00:00.000-07:00

Maintaining a Sterile Urinary Tract: The Role of Antimicrobial Peptides
Urol. 2009 May 16

Ali AS, Townes CL, Hall J, Pickard RS.
Newcastle University, Newcastle upon Tyne, United Kingdom.

PURPOSE: The normally sterile urinary tract is constantly challenged by microbial invasion leading to a high prevalence of isolated, recurrent and catheter associated urinary tract infection. The continuous emergence of bacterial resistance following overuse of traditional antibiotics requires the urgent development of alternative treatment strategies. The involvement of innate immune mechanisms in host defense is an emerging field of microbiological research with recent work focusing on the urinary tract. We performed a comprehensive literature review to establish the current level of knowledge concerning the role of innate immunity and specifically antimicrobial peptides within the human urinary tract.

MATERIALS AND METHODS: A systematic review of the literature was performed by searching PubMed(R) from January 1988 to September 2008. Electronic searches were limited to the English language using the key words antimicrobial, peptide and urinary. Reference lists from relevant reviews were hand searched and appropriate articles were retrieved. The proceedings of conferences held in the last 2 years by the American Urological Association, European Association of Urology and British Association of Urological Surgeons were also searched.

RESULTS: Several defensive mechanisms have evolved in response to the threat of urinary infection, comprising physical factors and innate immune responses characterized by the expression of antimicrobial peptides. Antimicrobial peptides are small (less than 10 kDa), cationic and amphipathic peptides of variable length, sequence and structure with broad spectrum killing activity against a wide range of microorganisms including gram-positive and gram-negative bacteria. Several antimicrobial peptides have been identified in the urinary tract, and the amount and type of antimicrobial peptides expressed vary according to tissue source and disease state. These differences may reflect altered levels of innate response and, hence, susceptibility to infection. Antimicrobial peptides are already being exploited therapeutically for skin and endovascular catheter infection, and prospects for useful application in the urinary tract are emerging.

CONCLUSIONS: Although investigation of antimicrobial peptide function in the human urinary tract is at an early stage, it is clear that there is considerable potential for the future design of novel therapeutic strategies. More knowledge is needed concerning the pathway of involvement of antimicrobial peptides in the maintenance of urinary tract sterility and the ways in which this is altered during active infection.

PMID: 19447447 [PubMed - as supplied by publisher]

Prospective analysis of central venous catheter colonization and related factors

2009-05-19T06:52:00.000-07:00

Prospective analysis of central venous catheter colonization and related factors
Enferm Clin. 2009 May 14

Pérez Castro I, Iborra Obiols MI, Comas Munar MD, Yrurzun Andreu R, Sanz Moncusí M, Lahoz Simón C, Gómez Montoya MI, Comallonga Bartomeu T, Navasa Anadón M.
Institut de Malalties Digestives i Metabóliques, Hospital Clínic de Barcelona, Barcelona, España.

OBJECTIVE: To evaluate the incidence of central venous catheter (CVC) colonization in inpatient units of the Institut de Malalties Digestives i Metabòliques (IMDiM) of Hospital Clinic (Barcelona, Spain) with a view to reducing the risk of infection.

METHOD: A 4-month descriptive, prospective and longitudinal study was performed. A total of 230 patients admitted to the IMDiM with CVC were included during the study period. At catheter removal, the tip was cultured and, if the patient had fever, two blood cultures were also obtained. A database was created. Data were analyzed using SPSS v.11.0. Variables were compared with the Chi-square and Student's t-tests and a multivariate analysis was performed using Cox logistic regression. A value of P 0.05

RESULTS: Catheter tip culture was positive in 45.2%. The rate of catheter-related bloodstream infections was 2.9 per thousand catheter-days, which was clinically significant. The probability of catheter tip contamination 10 days after placement was 25%. Multivariate analysis revealed that the independent variables associated with a higher risk of infection were catheter type, changes of dressing, and infected bacterial stopcocks.

CONCLUSIONS: These results suggest that: 1) the protocol for catheter insertion and care should be reviewed and updated, 2) catheter removal should be considered after the 10th day, 3) the appropriate type of catheter should be selected, the catheter with the lowest number of lumens should be used, and changes of catheter dressing should be reduced.

PMID: 19447058 [PubMed - as supplied by publisher]

Daptomycin: rationale and role in the management of skin and soft tissue infections.

2008-12-30T05:46:00.000-08:00

Daptomycin: rationale and role in the management of skin and soft tissue infections.
J Antimicrob Chemother. 2008 Nov

Seaton RA.
Department of Infectious Diseases and General Medicine, Brownlee Centre, Gartnavel General Hospital, 1053 Great Western Road, Glasgow, Scotland, UK. andrew.seaton@ggc.scot.nhs.uk

The emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA) and glycopeptide tolerance in S. aureus has underlined the importance of the newer anti-MRSA agents, particularly in the management of complicated skin and soft tissue infections (cSSTIs). The novel cyclic lipopeptide antibiotic daptomycin shows marked in vitro cidality against MRSA compared with both vancomycin and linezolid. Although comparative studies in cSSTIs have demonstrated non-inferiority with vancomycin and semi-synthetic penicillins, data from both clinical trials and observational studies suggest in vivo cidality as evidenced by rapid resolution of clinical signs of local inflammation and reduced duration of therapy. Overall success in SSTI post-marketing studies is >90%, and >88% in MRSA-infected patients, with no difference in the outcome observed between those with complicated versus uncomplicated infections. When used at licensed doses (4-6 mg/kg), daptomycin is safe and effective in SSTIs with significant muscle toxicity occurring in only 0.4% to 2.5% of patients. Clinical failure in daptomycin-treated SSTIs is associated with severity of infection (creatinine clearance <30>

Journal of Antimicrorbial Chemotherapy

Daptomycin for methicillin-resistant Staphylococcus aureus infections of the spine.

2008-12-30T05:40:00.000-08:00

Daptomycin for methicillin-resistant Staphylococcus aureus infections of the spine.
Spine J. 2008 Dec 26

Burdette SD.
Department of Medicine, Wright State University Boonshoft School of Medicine, Dayton, OH 45409, USA.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) infection is increasingly common. Treatment with vancomycin-based therapy is often unsuccessful. Daptomycin is a relatively new lipopeptide antibiotic with potent activity against MRSA.

PURPOSE: To describe the successful management of MRSA infection involving the spine.

STUDY DESIGN: Two case reports of MRSA infection, one involving epidural and lumbar subdural abscesses, the other with osteomyelitis and discitis.

METHODS: Two cases are described, one with lumbar epidural and subdural abscesses and the other with osteomyelitis and discitis of the spine. Switching from vancomycin to daptomycin plus rifampin-based therapy resulted in patient improvement that allowed discharge from the hospital.

RESULTS: Both patients recovered fully from their infection.

CONCLUSIONS: Daptomycin is a safe and effective option for the treatment of MRSA infection involving the spine.

PMID: 19112049 [PubMed - as supplied by publisher]

Antibiotic choices by paediatric residents and recently graduated paediatricians for typical infectious disease problems in children.

2008-11-28T08:19:00.000-08:00

Antibiotic choices by paediatric residents and recently graduated paediatricians for typical infectious disease problems in children.

Paediatr Child Health. 2006 Dec

Smart K, Lemay JF, Kellner JD.
Pediatric Emergency Medicine.

OBJECTIVE: To evaluate antibiotic choices and recommendations for duration of therapy made by paediatric residents (PRs) and recently graduated paediatricians (RGPs) in several typical infectious disease conditions.

METHODS: In autumn 2002, a two-page questionnaire was sent to 276 core PRs in Canadian residency programs and to a random selection of 276 RGPs from across Canada. The questionnaire described 10 scenarios: otitis media, pharyngitis, sinusitis, bronchopneumonia, lobar pneumonia, meningitis, pyelonephritis, osteomyelitis, cellulitis, and fever and neutropenia. The participants were asked primarily about initial antibiotic selection and duration of treatment for each scenario.

RESULTS: There were 251 participants (overall response rate of 45%). The two most common antibiotic recommendations constituted 85% or more of the total for all scenarios except acute otitis media, sinusitis, cellulitis, and fever and neutropenia. There was a twofold or more difference in the range of recommended duration of treatment for all scenarios and a threefold or more difference for sinusitis, meningitis and osteomyelitis. PRs were more likely than RGPs to use broader spectrum cephalosporins for pneumococcal pneumonia (33% versus 15%, respectively; P=0.001) and to treat sinusitis for just five to 10 days (39% versus 22%, respectively; P=0.01). Also, 33% of all participants recommended amoxicillin/clavulanate or a cephalosporin rather than amoxicillin for sinusitis.

CONCLUSION: PRs and RGPs made similar and reasonable recommendations, largely in line with published guidelines, for most of the infectious disease scenarios presented. For some conditions, a significant minority of respondents unnecessarily recommended broad-spectrum antibiotics. The most variable responses were for duration of treatment, reflecting the lack of certainty in the published evidence base for many conditions.

PMID: 19030247 [PubMed - in process]

Aerosol antibiotics: considerations in pharmacological and clinical evaluation.

2008-11-28T07:59:00.000-08:00

Aerosol antibiotics: considerations in pharmacological and clinical evaluation.

Curr Opin Biotechnol. 2008 Nov 24.

Dudley MN, Loutit J, Griffith DC.
Mpex Pharmaceuticals, San Diego, CA 92121, United States.

Increasing antibiotic resistance and lack of R&D productivity of new classes of antimicrobial agents directed against Gram-negative bacteria necessitate new approaches to maximize the efficacy of existing classes of drugs. Direct administration of drugs to the lung via the inhalational route provides for high concentrations at the target site of action in patients with pulmonary infections. The efficacy of aerosol antibiotic administration has been best demonstrated with aerosolized tobramycin in the management of chronic infections because of Pseudomonas aeruginosa in cystic fibrosis (CF) patients. Unfortunately, inconvenient regimens leading to poor patient adherence to therapy, and the increasing frequency of multidrug-resistant strains have necessitated the search for additional agents. Integration of aerosol science, PK-PD and clinical trial designs are important for the development and evaluation of these new aerosol agents in both chronic infections (e.g. CF and chronic obstructive pulmonary disease (COPD)) as well as acute infections (e.g. bacterial pneumonias).

This review outlines important considerations and recent progress in this emerging area.

PubMed

Efficacy of oral beta-lactam versus non-beta-lactam treatment of uncomplicated cellulitis.

2008-11-22T03:12:00.000-08:00

Efficacy of oral beta-lactam versus non-beta-lactam treatment of uncomplicated cellulitis.

Am J Med. 2008
Madaras-Kelly KJ, Remington RE, Oliphant CM, Sloan KL, Bearden DT.
College of Pharmacy, Idaho State University, Boise, Idaho, USA. KMK@otc.isu.edu

BACKGROUND: Preferred therapy for purulent skin and soft tissue infections is incision and drainage, but many infections cannot be drained. Empiric therapies for these infections are ill-defined in the era of community-acquired methicillin-resistant Staphylococcus aureus.

METHODS: A multicenter retrospective cohort study of outpatients treated for cellulitis was conducted to compare clinical failure rates of oral beta-lactam and non-beta-lactam treatments. Exclusion criteria included purulent infection requiring incision and drainage, complicated skin and soft tissue infection, chronic ulceration, and intravenous antibiotics. Failure rates were compared using logistic regression to adjust for both covariates associated with failure and a propensity score for beta-lactam treatment.

RESULTS: Of 2977 patients, 861 met inclusion criteria and were classified by treatment: beta-lactam (n = 631) or non-beta-lactam therapy (n = 230). Failure rates were 14.7% versus 17.0% (odds ratio [OR] 0.85, 95% confidence interval [CI], 0.56-1.31) for beta-lactam and non-beta-lactam therapy, respectively. Failure was associated with: age (P = .02), acute symptom severity (P = .03), animal bites (P = .03), Charlson score > 3 (P = .02), and histamine-2 receptor antagonist use (P = .09). Relative efficacy of beta-lactam therapy was greater after adjustment for factors associated with failure but remained statistically insignificant (adjusted OR 0.81, 95% CI, 0.53-1.24); adjusted including propensity score covariate (OR 0.71, 95% CI, 0.45-1.13). Discontinuation due to adverse effects differed between beta-lactam (0.5%) and non-beta-lactam (2.2%) therapies (P = .04).

CONCLUSION: There was no significant difference in clinical failure between beta-lactam and non-beta-lactam antibiotics for the treatment of uncomplicated cellulitis. Increased discontinuation due to adverse events with non-beta-lactam therapy was observed.

ScienceDirect

Providing outpatient antibiotic therapy for cellulitis in primary care.

2008-11-22T03:06:00.000-08:00

Providing outpatient antibiotic therapy for cellulitis in primary care.
Br J Community Nurs. 2008 Nov 7

Nazarko L.

Outpatient parenteral antimicrobial therapy (OPAT) is becoming more widespread. OPAT therapy can be used to treat certain patients who have cellulitis. The decision as to which patients to treat at home must be based on local PCT guidelines—not all patients are suitable for OPAT. OPAT improves patient quality of life by delivering care in the patient's home. This is highly skilled work and the community nurse must have appropriate training and support in order to gain the skills required.

PMID: 18981968 [PubMed - as supplied by publisher]

Outpatient parenteral antibiotic therapy with daptomycin: insights from a patient registry

2008-11-22T02:58:00.000-08:00

Outpatient parenteral antibiotic therapy with daptomycin: insights from a patient registry

Int J Clin Pract. 2008 Aug

Martone WJ, Lindfield KC, Katz DE.
Cubist Pharmaceuticals, Inc., Lexington, MA 02421, USA. william.martone@cubist.com

AIM: To compare and contrast the characteristics and clinical outcomes of patients who have received daptomycin as outpatients and inpatients.

METHODS: The Cubicin Outcomes Registry and Experience (CORE) is a retrospective chart review of patients who have received daptomycin in participating institutions. Patients treated in 2005 were included in this analysis. Demographic characteristics and clinical outcomes (success = cured + improved) were compared among patients who received outpatient parenteral antibiotic therapy (OPAT) and patients who had received inpatient parenteral antibiotic therapy (IPAT).

RESULTS: Of 1172 patients reported by 52 CORE 2005 participating institutions/investigators, 949 (81.0%) patients were evaluable: 539 (56.8%) received OPAT (OPAT patients), and 410 (43.2%) received only IPAT (IPAT patients). Of the 539 OPAT patients, 273 (50.6%) also received some IPAT, usually preceding OPAT therapy. Successful outcomes [no. of successes/(no. of successes + no. of failures)] for OPAT patients vs. IPAT patients were 94.6% and 86.3% respectively (chi-square test, p <>

CONCLUSIONS: Outpatient parenteral antibiotic therapy use was common (539/949 or 56.8%) among patients in CORE 2005. Clinical outcomes among OPAT patients appeared at least as good as or better than IPAT patients. Better outcomes among OPAT patients were most likely because of patient selection for OPAT. Additional studies should focus on clinical characteristics of patients who would be ideal candidates for daptomycin OPAT.

Wiley InterScience

Daptomycin in bone and joint infections: a review of the literature.

2008-11-12T06:21:00.000-08:00

Daptomycin in bone and joint infections: a review of the literature.

Arch Orthop Trauma Surg. 2008 Nov 7

Rice DA, Mendez-Vigo L.
St. Joseph's/Candler Health System, Savannah, GA, USA.

INTRODUCTION: To review the pharmacology, pharmacokinetics, efficacy, and safety of daptomycin, a novel antibiotic for the treatment of bone and joint infections, a literature search of relevant articles was conducted.

MATERIALS AND METHODS: A PubMed/MEDLINE search (1990-April 2008) to identify relevant English-language literature was conducted. Search terms included bone and joint infection, osteomyelitis, daptomycin, and methicillin-resistant Staphylococcus aureus (MRSA). Additional articles were identified by reviewing the bibliographies of articles cited. Programs and abstracts from infectious disease meetings were searched, and prescribing information of antibiotics indicated for bone and joint infections consulted. All articles identified from data sources published in English were evaluated.

RESULTS: Caused primarily by Gram-positive pathogens such as S. aureus and, to a lesser extent, Enterococcus faecalis, bone and joint infections are difficult to treat successfully. Surgical intervention and prolonged courses of antibiotics are frequently required, and failure of first-line antibiotic therapy is common. The emergence of S. aureus strains with reduced susceptibility to vancomycin, the longstanding gold standard for bone and joint infections, has complicated the clinical scenario. Few randomized trials comparing the efficacy of different antibiotics for bone and joint infections exist. Daptomycin, a novel intravenous lipopeptide antibiotic, has shown potent in vitro activity against a broad spectrum of Gram-positive bacteria, including many resistant pathogens commonly associated with bone and joint infections such as MRSA and vancomycin-resistant E. faecalis. Early clinical investigation of daptomycin in bone and joint infections unresponsive to antibiotics, such as vancomycin, has found a cure rate of approximately 80%, with a low incidence of adverse events and drug resistance.

CONCLUSION: Further studies are warranted to determine if limited clinical evidence, described in individual case reports and a daptomycin-specific retrospective registry, suggests daptomycin is a promising option for patients with bone and joint infections such as MRSA osteomyelitis.

Springerlink

Pivmecillinam versus sulfamethizole for short-term treatment of uncomplicated acute cystitis in general practice: A randomized controlled trial.

2008-11-12T05:54:00.000-08:00

Pivmecillinam versus sulfamethizole for short-term treatment of uncomplicated acute cystitis in general practice: A randomized controlled trial.

Scand J Prim Health Care. 2008 Nov

Bjerrum L, Gahrn-Hansen B, Grinsted P.
Research Unit for General Practice, University of Southern Denmark.

Objective.

To investigate whether short-term treatment with pivmecillinam was more effective than sulfamethizole in patients with acute uncomplicated urinary tract infection (UTI). Design. Randomized controlled trial. Setting. General practice, Denmark.

Subjects.

Patients (n =167) with uncomplicated UTI confirmed by positive urine phase-contrast microscopy. Main outcome measures. Drug efficacy based on clinical and bacteriological cure.

Results.

Urinary symptoms disappeared first in patients treated with pivmecillinam, but after five days there was no significant difference in clinical cure rate between the two antibiotics. At the follow-up visit 7-10 days after initiation of treatment, 95.4% of patients treated with pivmecillinam and 92.6% of patients treated with sulfamethizole had no persistent cystitis symptoms (difference 2.8%, CI -4.5%; 10.0%).

Bacteriological cure was observed in 68.8% of patients randomized to pivmecillinam and in 77.9% randomized to sulfamethizole (difference -9.2%, CI -24.7%; 6.3%). Some 26.8% of patients randomized to pivmecillinam experienced a new UTI within 6 months after treatment compared with 18.4% of patients randomized to sulfamethizole (difference 8.4%, CI -4.5%;21.4%). No patients developed septicaemia with urinary pathogens within one year after initial treatment.

Conclusion.

Patients treated with a three-day regime of pivmecillinam experienced faster relief of symptoms compared with patients treated with a three-day regime of sulfamethizole. Five days after initiation of treatment there was no significant difference in clinical and bacteriological cure between the two antibiotic regimes.

Informaworld

Do we still need the aminoglycosides?

2008-11-04T05:17:00.000-08:00

Do we still need the aminoglycosides?

Int J Antimicrob Agents. 2008 Oct 29

Durante-Mangoni E, Grammatikos A, Utili R, Falagas ME.
Unit of Infectious & Transplant Medicine, 2nd University of Naples, Monaldi Hospital, Naples, Italy.

Since the introduction into clinical practice of the aminoglycoside class of antibiotics, a number of other antimicrobial agents with improved safety profile have entered the market. Studies have failed to demonstrate the superiority of aminoglycoside-containing regimens in a number of infection settings. This has raised doubts regarding the actual clinical utility of aminoglycosides. However, the recent emergence of infections due to Gram-negative bacterial strains with advanced patterns of antimicrobial resistance has prompted physicians to reconsider these 'old' antibacterial agents. This revived interest in the use of aminoglycosides has brought back to light the debate on the two major issues related to these compounds, namely the spectrum of antimicrobial susceptibility and toxicity. Although some of the aminoglycosides retain activity against the majority of Gram-negative clinical bacterial isolates in many parts of the world, the relatively frequent occurrence of nephrotoxicity and ototoxicity during aminoglycoside treatment make physicians reluctant to use these compounds in everyday practice. We believe that recent advances in the understanding of the effect of various dosage schedules of aminoglycosides on toxicity combined with the retained (to a considerable degree) activity against the majority of Gram-negative bacterial isolates make this class of antibiotics still valuable in today's clinical practice.

PMID: 18976888 [PubMed - as supplied by publisher]

Rational antibiotic therapy of urinary tract infections

2008-11-04T05:14:00.000-08:00

Rational antibiotic therapy of urinary tract infections

Med Monatsschr Pharm. 2008 Oct

Wagenlehner FM, Naber KG, Weidner W.
Klinik und Poliklinik für Urologie und Kinderurologie, Justus-Liebig-Universität Giessen, Rudolf-Buchheim-Str. 7, 35385 Giessen. Wagenlehner@AOL.com

Rational antibiotic therapy of urinary tract infections Urinary tract infections (UTI) are frequent infections in the outpatient and nosocomial setting. Generally UTI can be stratified into uncomplicated and complicated infections with respect to treatment options. Uncomplicated UTI are mainly caused by E. coli, whereas complicated UTI exhibit a broader bacterial spectrum with a higher rate of multiresistant uropathogens. On the other hand increasing resistance rates are also found in uncomplicated UTI, e.g. against aminopenicillins, Co-trimoxazol and increasingly also fluoroquinolones. This fact has to be considered in the empirical therapy. Recurrent UTI are frequently found in young, sexually active women, and postmenopausal women. In complicated UTI the complicating factors have to be diagnosed and treated additionally to the antibiotic treatment. If not treated, a severe UTI and urosepsis can develop.

PMID: 18972869 [PubMed - in process]

Paromomycin.

2008-10-26T07:46:00.000-07:00

Paromomycin

Trans R Soc Trop Med Hyg. 2008 Oct 21

Davidson RN, den Boer M, Ritmeijer K.
Department of Infection and Tropical Medicine, Lister Unit, Northwick Park Hospital, Harrow, Middlesex HA1 3UJ, UK.

Paromomycin is an aminoglycoside that is active against Gram-negative and many Gram-positive bacteria as well as some protozoa and cestodes. It is out of use as an antibiotic but was licensed in 2007 in India as an effective, well tolerated and affordable treatment for visceral leishmaniasis (VL) at a dose of 11mg/kg (base) for 21 days. Currently, the non-profit group Drugs for Neglected Diseases Initiative is conducting studies on paromomycin (as monotherapy and in combination) in VL in Africa, and the Institute for OneWorld Health is conducting a Phase IV study in India. Paromomycin in combination with sodium stibogluconate has proven to be effective in African and Indian VL and improves survival in African VL. To prevent the emergence of drug-resistant leishmaniasis in areas of anthroponotic transmission (India and Africa), paromomycin should be used as part of combination therapy for VL. Further trials testing different combinations are much needed. In addition, the distribution of paromomycin (like other drugs for leishmaniasis) should be well regulated and preferably restricted to the public sector. These strategies should ensure the longevity of paromomycin as a useful drug for VL

Elsevier

Isolation, Structure, and Antibacterial Activity of Philipimycin

2008-08-15T04:05:00.000-07:00

Isolation, Structure, and Antibacterial Activity of Philipimycin, A Thiazolyl Peptide Discovered from Actinoplanes philippinensis MA7347.

J Am Chem Soc. 2008 Aug

Zhang C, Occi J, Masurekar P, Barrett JF, Zink DL, Smith S, Onishi R, Ha S, Salazar O, Genilloud O, Basilio A, Vicente F, Gill C, Hickey EJ, Dorso K, Motyl M, Singh SB.

Bacterial resistance to antibiotics, particularly to multiple drug resistant antibiotics, is becoming cause for significant concern. The only really viable course of action is to discover new antibiotics with novel mode of actions. Thiazolyl peptides are a class of natural products that are architecturally complex potent antibiotics but generally suffer from poor solubility and pharmaceutical properties. To discover new thiazolyl peptides potentially with better desired properties, we designed a highly specific assay with a pair of thiazomycin sensitive and resistant strains of Staphylococcus aureus, which led to the discovery of philipimycin, a new thiazolyl peptide glycoside. It was isolated along with an acid-catalyzed degradation product by bioassay-guided fractionation. Structure of both compounds was elucidated by extensive application of 2D NMR, 1D TOCSY, and HRESIFT-MS/MS. Both compounds showed strong antibacterial activities against Gram-positive bacteria including MRSA and exhibited MIC values ranging from 0.015 to 1 mug/mL. Philipimycin was significantly more potent than the degradation product. Both compounds showed selective inhibition of protein synthesis, indicating that they targeted the ribosome. Philipimycin was effective in vivo in a mouse model of S. aureus infection exhibiting an ED 50 value of 8.4 mg/kg. The docking studies of philipimycin suggested that a part of the molecule interacts with the ribosome and another part with Pro 23, Pro 22, and Pro 26 of L11 protein, which helped in explaining the differential of activities between the sensitive and resistant strains. The design and execution of the bioassay, the isolation, structure, in vitro and in vivo antibacterial activity, and docking studies of philipimycin and its degradation product are described.

PMID: 18698773 [PubMed - as supplied by publisher]

Tobramycin-induced hepatotoxicity

2008-08-07T18:58:00.000-07:00

Tobramycin-induced hepatotoxicity

Ann Pharmacother. 2007 Dec

Nisly SA, Ray SM, Moye RA.
College of Pharmacy and Health Sciences, Butler University, Indianapolis, IN, USA.

OBJECTIVE: To report a case of tobramycin-induced hepatotoxicity.

CASE SUMMARY: A 20-year-old female was hospitalized for treatment of Pseudomonas aeruginosa bacteremia and osteomyelitis. Empiric intravenous antibiotic therapy with piperacillin/tazobactam, vancomycin, and ciprofloxacin was started, and based on the results of culture and sensitivity testing, was changed to intravenous ceftazidime and tobramycin 70 mg every 8 hours on hospital day 3. Liver enzyme levels then increased over days 3-6. Tests for hepatitis A, B, and C were all nonreactive, and HIV testing was negative. On day 8, therapy was changed from ceftazidime to piperacillin/tazobactam and the tobramycin dose was increased to 100 mg every 8 hours. Due to a continued increase in total bilirubin, aspartate aminotransferase, and alanine aminotransferase, piperacillin/tazobactam was discontinued and aztreonam was started on day 10. All antibiotics were stopped on day 12 and the elevated liver parameters began to decrease. Aztreonam and ciprofloxacin were restarted on day 16, and most laboratory test results returned to baseline levels by day 19; total bilirubin and alkaline phosphatase decreased to lower than baseline values.

DISCUSSION: This case illustrates a possible occurrence of tobramycin-induced hepatotoxicity. Liver enzymes rose when tobramycin therapy was initiated, markedly increased when the tobramycin dose was increased, then resolved upon discontinuation of therapy. Other medication-related causes were ruled out by temporal relationship or rechallenge (aztreonam). Use of the Naranjo probability scale indicated a possible relationship between hepatotoxicity and tobramycin therapy. Other adverse reaction scales specific for evaluation of drug-induced liver disease were also used. Both the Council for International Organizations of Medical Sciences and Maria and Victorino scales indicated a probable likelihood of tobramycin-induced hepatotoxicity. This patient was not rechallenged with tobramycin due to the highly suggestive timeline present, lack of specific symptoms, and unnecessary risk to the patient.

CONCLUSIONS: Although no other case reports on this interaction have been published through October 9, 2007, historical data from tertiary sources reveal the possibility of aminoglycoside-induced hepatotoxicity; therefore, tobramycin-induced hepatotoxicity cannot be ruled out in this patient. Clinicians should be aware of this adverse event.

Annals of Pharmacotherapy

Neuralgic Amyotrophy Associated with Antibiotic Therapy

2008-08-07T18:51:00.000-07:00

Neuralgic Amyotrophy Associated with Antibiotic Therapy

Ann Pharmacother. 2008 Aug

Finstad K, Guajardo JR, Scoville C.
Department of Child Health, University Hospital and Clinics, Columbia, MO.

OBJECTIVE: To report a case of neuralgic amyotrophy associated with antibiotic therapy.

CASE SUMMARY: A 22-year-old male with cystic fibrosis had been nonadherent to treatment for 4 years; when he returned to the clinic with symptoms, his forced expiratory volume in 1 second dropped from 84% predicted to 43% predicted. He was admitted to the hospital for treatment after failing to improve on oral ciprofloxacin and inhaled tobramycin. Treatment was initiated with intravenous tobramycin 560 mg daily and piperacillin/tazobactam 4.5 g infused every 6 hours. He continued inhaled tobramycin 300 mg twice daily, his home doses of pancreatic replacement enzymes and vitamins, albuterol 2.5 mg by high flow nebulizer (HFN) 4 times daily, and dornase alpha 2.5 by HFN daily. Sputum cultures were positive for methicillin-resistant Staphylococcus aureus, and intravenous vancomycin 1 g every 8 hours was added to the treatment regimen on hospital day 7. The patient developed bilateral shoulder pain followed by decreased function of his upper extremities 2 days later. He was treated with oral ibuprofen 600 mg every 6 h and oral cyclobenzaprine 5 mg daily, which improved his pain, but the shoulder stiffness remained throughout his hospital stay and persisted for 2 months following discharge. These symptoms resolved but recurred rapidly (within 24 h) and were more debilitating following a second exposure to the same antibiotics at the same doses 8 months later when the patient was readmitted for treatment of another cystic fibrosis-related pulmonary exacerbation.

DISCUSSION: To our knowledge, this is the first case report illustrating neuralgic amyotrophy triggered by exposure to the antibiotics vancomycin, tobramycin, and piperacillin/tazobactam. After analysis of the case, ruling out other possibilities and using the Naranjo probability scale, we found that there is a highly probable likelihood that the symptoms presented by our patient were secondary to his drug therapy. Neuralgic amyotrophy is a rare condition of unknown etiology that has never before been associated with administration of these antibiotics, individually or in combination. Because of the specifics of the clinical history, we were unable to ascertain whether this complication was due to a single antibiotic or to the combination. It is quite possible that vancomycin was the only culprit, but impossible to ensure with the available evidence.

CONCLUSIONS: Clinicians should be aware of this adverse reaction when facing similar complex neurologic symptoms in patients who are receiving the antibiotic treatment described here, especially vancomycin.

PMID: 18682542 [PubMed - as supplied by publisher]

Tigecycline: a critical update.

2008-08-06T04:19:00.000-07:00

Tigecycline: a critical update.
J Chemother. 2008 Jul

Shakil S, Akram M, Khan AU.
Interdisciplinary Biotechnology Unit, Aligarh Muslim University, India.

Tigecycline is the first Food and Drug Administration (FDA) approved glycylcycline antibiotic. It has shown remarkable in vitro activity against a wide variety of gram-positive, gram-negative and anaerobic bacteria including many multidrug resistant (MDR) strains. However, it has minimal activity against Pseudomonas aeruginosa and Proteus spp. To date, little resistance to tigecycline has been reported. Clinical trials studying complicated skin and skin-structure infections (cSSSIs) demonstrated that tigecycline has equivalent efficacy and safety compared with the combination of vancomycin and aztreonam. For complicated intra-abdominal infections (cIAIs), tigecycline was found to be as effective as imipenem/cilastatin. Adverse events related to tigecycline therapy, i.e. nausea and vomiting, were tolerable. Currently available data suggest that tigecycline may play an important role in the future as a monotherapy alternative to older broad-spectrum antibiotics, such as advanced generation cephalosporins, carbapenems, fluoroquinolones, piperacillin/tazobactam, and gram-positive directed agents (e.g. daptomycin, linezolid and quinupristin/dalfopristin) for which resistance is being increasingly reported from all parts of the world.

PMID: 18676218 [PubMed - in process]

Daptomycin, a lipopeptide antibiotic in clinical practice.

2008-08-04T01:46:00.000-07:00

Daptomycin, a lipopeptide antibiotic in clinical practice.
Curr Opin Investig Drugs. 2008 Aug

Weis F, Beiras-Fernandez A, Schelling G.
Department of Anesthesiology, University Hospital Grosshader, Marchioninistrasse 15, 81377, Munich, Germany. Florian.Weis@med.uni-muenchen.de.

Gram-positive cocci are one of the leading causes of infections in clinical medicine. Since the invention of antibiotic substances, multidrug resistance is a major problem in the treatment of such infections. Methicillin-resistant Staphylococcus aureus (MRSA) is responsible for 60% of nosocomial infections in the US. The first-choice drug used in these cases is the glycopeptide vancomycin; however, vancomycin is associated with a significant number of adverse side effects, such as nephro- and ototoxicity. Thus, the discovery of new drugs against MRSA and other multidrug-resistant cocci is of utmost interest. Daptomycin, a lipopeptide, is one of these new drugs and has been successfully used in the treatment of complicated skin and skin-structure infections and right-sided endocarditis. Because of its potency and pharmacological profile, it is increasingly used for new indications not yet approved by the FDA. The purpose of this article is to provide an overview of daptomycin, with particular emphasis on potential new indications for which it could be used in the future.

PubMed

Bacteriophage therapy in children: Facts and prospects

2008-08-04T01:16:00.000-07:00

Bacteriophage therapy in children: Facts and prospects

Med Sci Monit. 2008 Aug

Fortuna W, Miedzybrodzki R, Weber-Dabrowska B, Gorski A.
Bacteriophage Laboratory, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland and Phage Therapy Unit, Healthcare Center, Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wrocław, Poland.

Data from the World Health Organization confirm a decrease in the effectiveness of antibiotic therapy. The spread of bacteria resistant to several groups of antibiotics creates more problems in the treatment of various diseases, especially in children. It is possible that pharmacological agents may prove to be ineffective in curing infections caused by resistant pathogens, and this could lead to a post-antibiotic era. It is necessary to extend the arsenal of the available therapeutic tools. Bacteriophages have long been used therapeutically and prophylactically in children. In the beginnings of phage therapy, enthusiasm prevailed over the rational methods used in contemporary controlled studies. Many people dealing with phages described cases of successful therapy, but did not conduct comparative studies. Nevertheless, phage administration seems to be safe, even in children after intravenous administration. The therapeutic and prophylactic application of phages is now experiencing a renaissance of interest. The authors' own recent analysis demonstrated the cost effectiveness of phages over antibiotic especially in the treatment of infections caused by multidrug-resistant bacteria. It can be concluded that the results of the therapeutic and prophylactic application of phages against multi-drug resistant pathogens are encouraging. It seems clear that bacteriophages need further evaluation regarding the control of bacterial infection in children.

PubMed

A new lipoglycopeptide: telavancin.

2008-08-04T01:11:00.000-07:00

A new lipoglycopeptide: telavancin.

Expert Opin Pharmacother. 2008 Aug

Nannini EC, Stryjewski ME.
Sanatorio Parque, Division of Infectious Diseases, Argentina.

The increase in infections caused by resistant Gram-positive organisms has led to an urgent need for new antibiotics. Telavancin is a rapidly bactericidal lipoglycopeptide with multiple mechanisms of action, including concentration-dependent inhibition of bacterial cell wall synthesis and disruption of the functional integrity of the cell membrane. Telavancin is active against a wide variety of Gram-positive organisms including Staphylococcus aureus with resistance to methicillin, reduced susceptibility to vancomycin, and full resistance to vancomycin. Telavacin is approximately 90% protein bound; it has a serum half-life of around 8 h and a prolonged postantibiotic effect, allowing once daily administration. Telavancin is eliminated principally through the urine, requiring dose adjustment in patients with renal impairment. The efficacy and safety of telavancin was demonstrated in a large program of patients with complicated skin and skin structure infections. Development of resistance has not been detected in clinical strains. Adverse events include taste disturbance, nausea and vomiting; a small proportion of patients experienced reversible increase in serum creatinine. Two large Phase III studies in patients with healthcare associated pneumonia were recently completed. Telavancin has the potential to become an important therapeutic option to treat serious infections produced by resistant Gram-positive cocci, particularly those caused by methicillin-resistant S. aureus.

Expert Opinion

Ciprofloxacin-induced acute cholestatic liver injury and associated renal failure. Case report and review.

2008-07-17T03:44:00.000-07:00

Ciprofloxacin-induced acute cholestatic liver injury and associated renal failure. Case report and review.
Minerva Gastroenterol Dietol. 2008 Sep

Dichiara AJ, Atkinson M, Goodman Z, Sherman KE.
Division of Digestive Diseases, Department of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA Kenneth.sherman@uc.edu.

Ciprofloxacin, a commonly prescribed fluoroquinolone antibiotic, has generally been well-tolerated; however, there are rare reports of associated hepatic failure or renal failure. We describe a case of a 65 year-old man with a history of ischemic cardiomyopathy who was treated with ciprofloxacin 500 mg twice daily for cellulitis. Six days into his treatment course, he developed acute cholestatic jaundice and acute anuric renal failure. Clinical, laboratory, and pathologic data suggest that the patient had developed reversible, severe ciprofloxacin-induced cholestatic liver injury and acute tubular necrosis requiring hemodialysis. Within two months of stopping the ciprofloxacin, the patient was off dialysis and back to his baseline creatinine in three months. Liver tests normalized by five months.

This report illustrates a case of cholestatic liver injury and renal failure involving ciprofloxacin use.

We review the literature regarding hepatic and renal injury as it relates to ciprofloxacin. To our knowledge, this represents the first case report of simultaneous acute cholestatic liver injury and renal failure secondary to ciprofloxacin.

PubMed

Tigecycline for the Treatment of Acinetobacter Infections: A Case Series September

2008-07-13T03:38:00.000-07:00

Tigecycline for the Treatment of Acinetobacter Infections: A Case Series September
Ann Pharmacother. 2008 Jul 9

Gallagher JC, Rouse HM.
Department of Pharmacy Practice, College of Pharmacy, University of Illinois at Chicago, Chicago, ILClinical Assistant Professor; Clinical Specialist, Infectious Diseases, Temple University School of Pharmacy, Philadelphia, PA.

BACKGROUND: Acinetobacter infections resistant to multiple classes of antibiotics have become prevalent in many institutions. Tigecycline has in vitro activity against Acinetobacter spp. and has been suggested as a therapeutic option in these infections.

OBJECTIVE: To describe the clinical and microbiologic outcomes of patients who received tigecycline for the treatment of infections caused by Acinetobacter spp. at our institution.

METHODS: A retrospective review was conducted of the medical records of 29 sequential patients who received tigecycline for treatment of Acinetobacter infections. The outcomes assessed for efficacy were clinical improvement or cure and microbiologic cure in evaluable patients.

RESULTS: Patients received tigecycline a median of 30 days into hospitalization for a median of 11 days. Common indications were pneumonia (15 pts.), bacteremia (6), and urinary tract infection (3). Positive clinical outcomes (clinical cure or improvement) were seen in 8 (28%) of 29 patients. Of the 25 microbiologically evaluable patients, 11 (44%) had resolution of their cultures. Eleven patients had susceptibility testing performed, and the median minimum inhibitory concentration was 4 microg/mL (range 3-8).

CONCLUSIONS: In this case series, most patients did not have clinically or microbiologically favorable outcomes with tigecycline therapy. No patient had an isolate that was fully susceptible to tigecycline. Data from more studies are needed before tigecycline can be recommended for the treatment of Acinetobacter infections.

Annals of Pharmacotherapy (PubMed)

Better outcomes through continuous infusion of time-dependent antibiotics to critically ill patients?

2008-07-13T03:33:00.000-07:00

Better outcomes through continuous infusion of time-dependent antibiotics to critically ill patients?
Curr Opin Crit Care. 2008 Aug

Roberts JA, Lipman J, Blot S, Rello J.
Burns Trauma and Critical Care Research Centre, University of Queensland, Brisbane, Queensland, Australia.

PURPOSE OF REVIEW: Increasing interest is being directed toward possible benefits associated with continuous infusion of time-dependent antibiotics such as beta-lactams and vancomycin to critically ill patients. The background, emerging evidence and practical considerations associated with continuous infusions are discussed.

RECENT FINDINGS: One large retrospective cohort study has found clinical outcome benefits of administering a beta-lactam antibiotic by extended infusion compared with bolus administration. This complements a smaller randomized controlled trial comparing continuous infusion and intermittent bolus administration. For vancomycin, clinical outcome benefits have only been shown in a ventilator-associated pneumonia cohort of critically ill patients. No clinical outcome studies have been conducted for other time-dependent antibiotics.

SUMMARY: Continuous infusion of vancomycin and beta-lactam antibiotics enables faster and more consistent attainment of therapeutic levels compared with intermittent bolus dosing. Although the clinical benefits have not been conclusively shown at this time, compelling pharmacokinetic/pharmacodynamic support for continuous infusion nevertheless exists. Given that critically ill patients may develop very large volumes of distribution as well as supranormal drug clearances, individualized therapy through the use of therapeutic drug monitoring is required. A definitive determination of the relative clinical efficacy of intermittent bolus and continuous administration of beta-lactams or vancomycin will only be achieved after a large-scale multicenter randomized controlled trial has been performed.

Lippincott, Williams & Wilkins

Reduction of unnecessary IV antibiotic days using general criteria for antibiotic switch.

2008-06-29T04:50:00.000-07:00

Reduction of unnecessary IV antibiotic days using general criteria for antibiotic switch.

Scand J Infect Dis. 2008

Waagsbø B, Sundøy A, Quist Paulsen E.
From the Medisinsk avdeling, Sørlandet Sykehus Kristiansand, Norway.

This study was designed to help physicians consider change from intravenous to oral antibiotic therapy for any infection from d 3 of hospital stay, by implementing guidelines for antibiotic switch. A 2-centre intervention study was conducted at Sorlandet Hospital HF Kristiansand and Arendal. All patients admitted to the Medical Clinic at these hospitals prescribed with intravenous antibiotics at hospitalization, were included. After collecting data in an observation period, antibiotic switch guidelines were launched in the respective departments of both hospitals. The length of unnecessary intravenous d, duration of hospital stay and outcome of treatment were compared before (observation group) and after (intervention group) the guidelines were implemented. Antibiotic switch was considered from d 3 and onward. The effect of switch guidelines implementation was measured as a reduction of unnecessary intravenous d. Duration of unnecessary intravenous antibiotic therapy was significantly reduced from 3.4 d in the observation group to 1.4 d in the intervention group. Unnecessary intravenous d were found to constitute 83% of total intravenous therapy duration in the observation group and 48% in the intervention group. Duration of hospital stay was significantly reduced from 7.0 to 6.3 d. There was no statistically significant difference in mortality rate, re-prescription of intravenous antibiotic therapy or re-admittance to the hospital. In conclusion, implementing antibiotic switch guidelines significantly reduces the duration of unnecessary intravenous antibiotic therapy. The switch guidelines were based on general criteria for antibiotic switch for any infection.

Informaworld

Antibiotic susceptibility patterns and clones of Pseudomonas aeruginosa in Swedish ICUs.

2008-06-29T04:25:00.000-07:00

Antibiotic susceptibility patterns and clones of Pseudomonas aeruginosa in Swedish ICUs.

Scand J Infect Dis. 2008

Erlandsson M, Gill H, Nordlinder D, Giske CG, Jonas D, Nilsson LE, Walther S, Hanberger H.
From the Division of Infectious Diseases, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linkoping University, Linkoping.

Pseudomonas aeruginosa is 1 of the bacteria most adaptive to anti-bacterial treatment. Previous studies have shown nosocomial spread and transmission of clonal strains of P. aeruginosa in European hospitals. In this study we investigated antibiotic susceptibility and clonality in 101 P. aeruginosa isolates from 88 patients admitted to 8 Swedish ICUs during 2002. We also compared phenotypes and genotypes of P. aeruginosa and carried out cluster analysis to determine if phenotypic data can be used for surveillance of clonal spread. All isolates were collected on clinical indication as part of the NPRS II study in Sweden and were subjected to AFLP analysis for genotyping. 68 isolates with unique genotypes were found. Phenotyping was performed using MIC values for 5 anti-pseudomonal agents. Almost 6% of the isolates were multi-drug resistant (MDR), and this figure rose to almost 8% when intermediate isolates were also included. We found probable clonal spread in 9 cases, but none of them was found to be an MDR strain. Phenotypical cluster analysis produced 40 clusters. Comparing partitions did not demonstrate any significant concordance between the typing methods. The conclusion of our study is that cross-transmission and clonal spread of MDR P. aeruginosa does not present a clinical problem in Swedish ICUs, but probable cross-transmission of non-MDR clones indicate a need for improved hygiene routines bedside. The phenotype clusters were not concordant with genotype clusters, and genotyping is still recommended for epidemiological tracking.

Informaworld

Treatment of Citrobacter koseri Infection with Ciprofloxacin and Cefotaxime in a Preterm Infant

2008-06-27T02:50:00.000-07:00

Treatment of Citrobacter koseri Infection with Ciprofloxacin and Cefotaxime in a Preterm Infant

Ann Pharmacother. 2008 Jun 24

McPherson C, Gal P, Ransom JL.
Departments of Neonatal Medicine and Pharmacy, Women's Hospital, Greensboro, NC.

OBJECTIVE: To report a case of successful treatment of Citrobacter koseri infection in a preterm infant as a means of challenging the current treatment recommendations on the basis of pharmacodynamic and pharmacokinetic considerations.

CASE SUMMARY: A premature infant was diagnosed with C. koseri sepsis after 3 weeks in intensive care. Concern for meningitis was based on the propensity for central nervous system (CNS) involvement with Citrobacter infection along with new findings of ventriculomegaly and hydrocephalus shown on cranial ultrasound (CUS).

The infant was treated with ciprofloxacin 10-20 mg/day and cefotaxime 100 mg/day for 21 days. After treatment, lumbar puncture was normal, follow-up CUS returned to baseline, and the infant passed a hearing screen after discharge. A favorable outcome was achieved in this case.

DISCUSSION: Approximately 76% of neonatal patients infected with C. koseri develop brain abscesses. The mortality rate for meningitis due to Citrobacter spp. is approximately 30%, and of the infants who survive, more than 80% have some degree of mental retardation. Third-generation cephalosporins and aminoglycosides are traditional therapies against this infection.

The current antibiotic strategies have failed to prevent the high rates of morbidity and mortality associated with Citrobacter infections. A possible basis for these poor outcomes is failure to apply appropriate pharmacokinetic and pharmacodynamic principles in selecting antibiotics that will achieve adequate concentrations to kill the bacteria in granulocytes within the CNS. Based on favorable sensitivity data, penetration into neutrophils and the CNS, and favorable toxicity profiles, ciprofloxacin and meropenem would appear to be the most appropriate antibiotic treatment options for systemic infection or meningitis caused by C. koseri.

CONCLUSIONS: Ciprofloxacin and meropenem should be considered antibiotic treatment options for systemic infection or meningitis caused by C. koseri.

Annals of Pharmcotherapy

Rational antibiotic therapy and the position of ampicillin/sulbactam.

2008-06-10T07:11:00.000-07:00

Rational antibiotic therapy and the position of ampicillin/sulbactam.
Int J Antimicrob Agents. 2008 Jun

Lode HM.
Research Centre for Medical Studies, Institute of Clinical Pharmacology, Charité Universitätsmedizin Berlin, Hohenzollerndamm 2, D-10717 Berlin, Germany.

In the current context of increasing antimicrobial resistance, it is important to use antibiotics rationally and to re-assess regularly the clinical usefulness of commonly used agents. This review focuses on the efficacy of the beta-lactam ampicillin co-administered with the beta-lactamase inhibitor sulbactam, either parenterally (ampicillin/sulbactam) or orally (sultamicillin), for the treatment of bacterial infections. Clinical findings from the past decade confirm the results of numerous older studies and together provide good evidence to support the continued use of ampicillin/sulbactam and sultamicillin in hospital- and community-acquired infections both in adults and children.

This is also recognised in recent published national and international guidelines, many of which recommend ampicillin/sulbactam as first-line therapy for various respiratory and skin infections.

PubMed

Novel Beta-lactam antibiotics derivatives: their new applications as gene reporters, antitumor prodrugs and enzyme inhibitors.

2008-05-14T04:46:00.000-07:00

Novel Beta-lactam antibiotics derivatives: their new applications as gene reporters, antitumor prodrugs and enzyme inhibitors.

Xing B, Rao J, Liu R.

Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, 637616. Bengang@ntu.edu.sg.

Since the antibiotic properties of penicillin were first noticed in the beginning of last century, beta-lactam based antibiotics have been well developed as miracle drugs for the therapy of bacterial infectious diseases in clinics. Recently, these "old" antibiotics and their relevant derivatives have also found new applications as gene reporters, anti-cancer prodrugs and enzyme inhibitors.

In this review, we will introduce the latest developments in the study of these new applications based on literatures reported over the last decade. The first section covers the recent developments of beta-lactam antibiotics as drugs against bacteria, the second section briefly discusses the occurrence of bacterial resistance and mechanistic studies of beta-lactam resistance in bacteria, the third section presents the current development of fluorogenic cephalosporin based beta-lactam probes for real-time imaging of gene expression, and the fourth section describes relevant studies on beta-lactam based substrates as anti-tumor prodrugs.

Beta-lactam substrates as protease inhibitors will be also described in the fifth section. The final section summarizes future perspectives for beta-lactam antibiotic derivatives as scaffolds in the fields of molecular imaging, drug delivery and enzymatic assays.

PMID: 18473935 [PubMed - in process]

Antibiotics to reduce post-tonsillectomy morbidity

2008-04-22T06:48:00.000-07:00

Antibiotics to reduce post-tonsillectomy morbidity

Cochrane Database Syst Rev. 2008 Apr

Dhiwakar M, Clement W, Supriya M, McKerrow W.

BACKGROUND: Tonsillectomy continues to be one of the most common surgical procedures performed in children and adults. Despite improvements in surgical and anaesthetic techniques, postoperative morbidity, mainly in the form of pain, remains a significant clinical problem. Postoperative bacterial infection of the tonsillar fossa has been proposed as an important factor causing pain and associated morbidity, and some studies have found a reduction in morbid outcomes following the administration of perioperative antibiotics.

OBJECTIVES: To determine whether perioperative antibiotics reduce pain and other morbid outcomes following tonsillectomy.

SEARCH STRATEGY: Cochrane ENT Group Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 1 2007), MEDLINE (1950 to 2007) and EMBASE (1974 to 2007) were searched. The date of the last search was March 2007.

SELECTION CRITERIA: All randomised controlled trials examining the impact of perioperative administration of systemic antibiotics on post-tonsillectomy morbidity in children or adults.

DATA COLLECTION AND ANALYSIS: Two authors independently collected data. Primary outcomes were pain, consumption of analgesia and secondary haemorrhage (defined as significant if patient re-admitted, transfused blood products or returned to theatre, and total if any documented haemorrhage). Secondary outcomes were fever, time taken to resume normal diet and activities and adverse events. Where possible, summary measures were generated using random-effects models.

MAIN RESULTS: Nine trials met the eligibility criteria. Most did not find a significant reduction in pain with antibiotics. Similarly, antibiotics were not shown to be effective in reducing the need for analgesics. Antibiotics were not associated with a reduction in significant secondary haemorrhage rates (Relative Risk (RR) 0.49, 95% CI 0.08 to 3.11, P = 0.45) or total secondary haemorrhage rates (RR 0.92, 95% CI 0.45 to 1.87, P = 0.81). With regard to secondary outcomes, antibiotics reduced the proportion of subjects with fever (RR 0.63, 95% CI 0.46 to 0.85, P = 0.002).

AUTHORS' CONCLUSIONS: The present review suggests that there is little or no evidence that antibiotics reduce the main morbid outcomes following tonsillectomy (i.e. pain, the need for analgesia or secondary haemorrhage rates). They do however appear to reduce fever. Some important methodological shortcomings exist in the included trials which are likely to have produced bias favouring antibiotics. We therefore advocate caution when prescribing antibiotics routinely to all patients undergoing tonsillectomy. Whether a subgroup of patients who might benefit from selective administration of antibiotics exists is unknown and needs to be explored in future trials.

PubMed

Emergence of Tetracycline-Resistant Vibrio cholerae O1 Serotype Inaba, in Kolkata, India.

2008-03-27T10:02:00.000-07:00

Emergence of Tetracycline-Resistant Vibrio cholerae O1 Serotype Inaba, in Kolkata, India.

Jpn J Infect Dis. 2008 Mar

Roychowdhury A, Pan A, Dutta D, Mukhopadhyay AK, Ramamurthy T, Nandy RK, Bhattacharya SK, Bhattacharya MK.
National Institute of Cholera and Enteric Diseases, Kolkata, India. mkbidh@gmail.com.

Out of 2,235 diarrheal stool samples collected from patients admitted to the Infectious Diseases Hospital, Kolkata, 343 cases were positive for Vibrio cholerae (341, V. cholerae O1 and 2, O139). During the year 2004, infections caused by V. cholerae serotype Ogawa and Inaba were 93 and 7%, respectively, while in 2005, the Inaba isolation rate rose to 88% as compared to 12% for Ogawa. Susceptibility to antimicrobial agents revealed that the O1 strains were resistant to multiple antibiotics (ampicillin, co-trimoxazole, furazolidone, nalidixic acid and streptomycin) with reduced susceptibility to ciprofloxacin. Increased isolation of tetracycline-resistant strains (27.3% for Ogawa and 15% for Inaba) was noted in 2005. It appears that the population might be at risk of infection by the Inaba serotype and that tetracycline may not be useful for the treatment.

Japanese Journal of Infectious Disease

Emergence of Vibrio cholerae O1 biotype El Tor serotype Inaba causing outbreaks of cholera in Orissa, India.

Jpn J Infect Dis. 2006 Aug

Pal BB, Khuntia HK, Samal SK, Das SS, Chhotray GP.
Pathology and Microbiology Division, Regional Medical Research Centre, Orissa, India.

A total of 431 rectal swabs, collected from acute diarrheal cases at a surveillance site and at different diarrheal outbreak areas of Orissa from May to October 2005, were bacteriologically analyzed. Out of 265 culture-positive samples, Vibrio cholerae O1 was isolated in 56 samples (20.8%), of which 37 were the Inaba serotype and 19 were the Ogawa. The antibiogram profile revealed that all the V. cholerae O1 Ogawa and Inaba serotypes were uniformly sensitive to ampicillin, chloramphenicol, gentamicin, ciprofloxacin, norfloxacin and tetracycline. The V. cholerae O1 Inaba serotypes were resistant to furazolidone and nalidixic acid, while the Ogawa strains were resistant to furazolidone, nalidixic acid and neomycin. The multiplex polymerase chain reaction (PCR) assay on some selected strains of both serotypes revealed that all the strains were positive for ctxA and tcpA genes showing biotype El Tor. The present study revealed the emergence of V. cholerae O1 biotype El Tor serotype Inaba, which caused sporadic outbreaks of cholera in 2005. The outbreaks of diarrheal disorders in one geographical area of the state (in the Pattamundai area, Kendrapara district) in 2005 were due to V. cholerae O1 Ogawa, whereas the other outbreaks in other areas (Puri, Khurda and Dhenkanal districts) from August to October 2005 were due to V. cholerae O1 serotype Inaba. This is the first report that an emergence of V. cholerae O1 serotype Inaba caused sporadic outbreaks of cholera in different parts of Orissa. Switching over of V. cholerae O1 Ogawa strains to Inaba, causing diarrheal outbreaks in Orissa, needs close monitoring.

Japanese Journal of Infectious Disease

Antibiotics for adults with clinically diagnosed acute rhinosinusitis: a meta-analysis of individual patient data.

2008-03-23T00:48:00.000-07:00

Antibiotics for adults with clinically diagnosed acute rhinosinusitis: a meta-analysis of individual patient data.

Lancet. 2008 Mar

Young J, De Sutter A, Merenstein D, van Essen GA, Kaiser L, Varonen H, Williamson I, Bucher HC.

Correspondence to: Jim Young, Basel Institute for Clinical Epidemiology, Hebelstrasse 10, University Hospital Basel, CH-4031 Basel, Switzerland

Basel Institute for Clinical Epidemiology, University Hospital Basel, Basel, Switzerland. jyoung@uhbs.ch

BACKGROUND: Primary-care physicians continue to overprescribe antibiotics for acute rhinosinusitis because distinction between viral and bacterial sinus infection is difficult. We undertook a meta-analysis of randomised trials based on individual patients' data to assess whether common signs and symptoms can be used to identify a subgroup of patients who benefit from antibiotics.

METHODS: We identified suitable trials--in which adult patients with rhinosinusitis-like complaints were randomly assigned to treatment with an antibiotic or a placebo--by searching the Cochrane Central Register of Controlled Trials, Medline, and Embase, and reference lists of reports describing such trials. Individual patients' data from 2547 adults in nine trials were checked and re-analysed. We assessed the overall effect of antibiotic treatment and the prognostic value of common signs and symptoms by the number needed to treat (NNT) with antibiotics to cure one additional patient.

FINDINGS: 15 patients with rhinosinusitis-like complaints would have to be given antibiotics before an additional patient was cured (95% CI NNT[benefit] 7 to NNT[harm] 190). Patients with purulent discharge in the pharynx took longer to cure than those without this sign; the NNT was 8 patients with this sign before one additional patient was cured (95% CI NNT[benefit] 4 to NNT[harm] 47). Patients who were older, reported symptoms for longer, or reported more severe symptoms also took longer to cure but were no more likely to benefit from antibiotics than other patients.

INTERPRETATION: Common clinical signs and symptoms cannot identify patients with rhinosinusitis for whom treatment is clearly justified. Antibiotics are not justified even if a patient reports symptoms for longer than 7-10 days.

The Lancet

Antibiotic treatment for Clostridium difficile-associated diarrhea in adults

2008-03-23T00:37:00.000-07:00

Antibiotic treatment for Clostridium difficile-associated diarrhea in adults

Cochrane Database Syst Rev. 2007 Jul

Nelson R.
Northern General Hospital, Department of General Surgery, Herries Road, Sheffield, Yorkshire, UK, S5 7AU. altohorn@btinternet.com

BACKGROUND: Clostridium difficile (C. difficile) is recognized as a frequent cause of antibiotic-associated diarrhea and colitis.

OBJECTIVES: The aim of this review is to establish the efficacy of antibiotic therapy for C. difficile-associated diarrhea (CDAD), to identify the most effective antibiotic treatment for CDAD in adults and to determine the need for stopping the causative antibiotic during therapy.

SEARCH STRATEGY: MEDLINE (1966 to 2006), EMBASE (1980 to 2006), Cochrane Central Database of Controlled Trials and the Cochrane IBD Review Group Specialized Trials Register were searched using the following search terms: "pseudomembranous colitis and randomized trial"; "Clostridium difficile and randomized trial"; "antibiotic associated diarrhea and randomized trial".

SELECTION CRITERIA: Only randomized, controlled trials assessing antibiotic treatment for CDAD were included in the review. Probiotic trials are excluded. The following outcomes were sought: initial resolution of diarrhea; initial conversion of stool to C. difficile cytotoxin and/or stool culture negative; recurrence of diarrhea; recurrence of fecal C. difficile cytotoxin and/or positive stool culture; patient response to cessation of prior antibiotic therapy; sepsis; emergent surgery: fecal diversion or colectomy; and death.

DATA COLLECTION AND ANALYSIS: Data were analyzed using the MetaView statistical package in Review Manager. For dichotomous outcomes, relative risks (RR) and 95% confidence intervals (CI) were derived from each study. When appropriate, the results of included studies were combined for each outcome. For dichotomous outcomes, pooled RR and 95% CI were calculated using a fixed effect model, except where significant heterogeneity was detected, at which time the random effects model was used. Data heterogeneity was calculated using MetaView.

MAIN RESULTS: Twelve studies (total of 1157 participants) involving patients with diarrhea who recently received antibiotics for an infection other than C. difficile were included. The definition of diarrhea ranged from at least two loose stools per day with an associated symptom such as rectal temperature > 38 (o)C, to at least six loose stools in 36 hours. Eight different antibiotics were investigated: vancomycin, metronidazole, fusidic acid, nitazoxanide, teicoplanin, rifampin, rifaximin and bacitracin. In paired comparisons, no single antibiotic was clearly superior to others, though teicoplanin, an antibiotic of limited availability and great cost, showed in some outcomes significant benefit over vancomycin and fusidic acid, and a trend towards benefit compared to metronidazole. Only one placebo controlled trial was done and no conclusions can be drawn from it due to small size and classification error. Only one study investigated synergistic antibiotic combination, metronidazole and rifampin, and there was no advantage to the drug combination.

AUTHORS' CONCLUSIONS: Current evidence leads to uncertainty whether mild CDAD needs to be treated. Patients with mild CDAD may resolve their symptoms as quickly without treatment. The only placebo-controlled study shows vancomycin's superior efficacy. However, this result should be treated with caution due to the small number of patients enrolled and the poor methodological quality of the trial. The Johnson study of asymptomatic carriers also shows that placebo is better than vancomycin or metronidazole for eliminating C. difficile in stool during follow-up. If one does decide to treat, then two goals of therapy need to be kept in mind: improvement of the patient's clinical condition and prevention of spread of C. difficile infection to other patients. Given these two considerations, one should choose the antibiotic that brings both symptomatic cure and bacteriologic cure.

In this regard, teicoplanin appears to be the best choice because the available evidence suggests that it is better than vancomycin for bacteriologic cure and has borderline superior effectiveness in terms of symptomatic cure. Teicoplanin is not readily available in the United States, which must be taken into account when making treatment decisions in that country.

Plain language summary

Antibiotic therapy for Clostridium difficile-associated diarrhea (CDAD) needs further investigation.Diarrhea may be a side effect of many commonly used antibiotics, and this is in some cases due to overgrowth of a bacterium called Clostridium difficile (C. difficile) in the colon after other bacteria have been killed. The seriousness of C. difficile-associated diarrhea can range from being a nuisance to a life threatening or even fatal disease. The treatment of CDAD is usually cessation of the initiating antibiotic and immediate administration of a new antibiotic. However each of these three strategies, cessation of the original antibiotic, immediate retreatment, and the choice of a new antibiotic are poorly supported by currently available evidence. The antibiotic that is most tested, vancomycin, is the one most prone to serious side effects. Seven other antibiotics are included in this review and within the limitations of the included studies, they each seem to be as effective as vancomycin.

The Cochrane Library

Pediatric fingertip injuries: do prophylactic antibiotics alter infection rates?

2008-03-20T16:59:00.000-07:00

Pediatric fingertip injuries: do prophylactic antibiotics alter infection rates?

Pediatr Emerg Care. 2008 Mar

Altergott C, Garcia FJ, Nager AL.
Department of Pediatrics, Division of Emergency Medicine, Childrens Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA 90027, USA. caltergott@chla.usc.edu

STUDY OBJECTIVE: Fingertip injuries are common in the pediatric population. Considerable controversy exists as to whether prophylactic antibiotics are necessary after repair of these injuries. Our goal was to compare the rate of bacterial infections among subgroups treated with and without prophylactic antibiotics. The study hypothesis was that infection rates were similar in the 2 groups.

METHODS: This was a prospective randomized control trial of pediatric patients presenting to an urban children's hospital with trauma to the distal fingertip, requiring repair. Patients were randomized to 2 groups: group 1 received no antibiotics, and group 2 received antibiotics (cephalexin). Repairs were performed in a standardized fashion, and all patients were reevaluated in the same emergency department in 48 hours and again by phone 7 days after repair. The primary outcome measure was the rate of infection at 7 days after repair.

RESULTS: One hundred forty-six patients were initially enrolled in the study, 11 patients were withdrawn before study completion, 69 subjects were randomized to the no-antibiotic group, and 66 subjects were randomized to the antibiotic group. There was 1 infection in each group at 7 days after repair. The infection rate was 1.45% (95% confidence interval, 0.04%-7.81%) for the no-antibiotic group and was 1.52% (95% confidence interval, 0.04%-8.16%) for the antibiotic group, not statistically significant (P = 1.00).

CONCLUSIONS: This study suggests that routine prophylactic antibiotics do not reduce the rate of infection after repair of distal fingertip injuries.

Lippincott, Williams & Wilkins

Trends in Resistance to Ciprofloxacin, Cefazolin, and Gentamicin in the Treatment of Bacterial Keratitis

2008-03-14T05:03:00.000-07:00

Trends in Resistance to Ciprofloxacin, Cefazolin, and Gentamicin in the Treatment of Bacterial Keratitis

J Ocul Pharmacol Ther. 2008 Mar 10

Afshari NA, Ma JJ, Duncan SM, Pineda R, Starr CE, Decroos FC, Johnson CS, Adelman RA.
Duke University Eye Center, Duke University Medical Center, Durham, NC.

Purpose: The aim of this study was to evaluate the microbial profile, resistance patterns, and antibiotic sensitivity of bacterial keratitis to three commonly used ocular antibiotics.

Methods: All cases of bacterial keratitis referred to the Massachusetts Eye and Ear Infirmary Microbiology Laboratory from two consecutive annual 10-month periods were reviewed. The bacterial profile and resistance to ciprofloxacin, cefazolin, and gentamicin was evaluated within the two intervals.

Results: Of the 485 cultures analyzed, 66.4% (322) were positive for bacterial isolates. Of these, 19.2% were polymicrobial, 87.5% were gram-positive, and 12.5% were gram-negative. The most prevalent isolate was coagulase-negative Staphylococcus (45.5%), followed by S. aureus (15.2%).

The resistance patterns for gram-positive bacteria for ciprofloxacin for the first versus second time interval were 12% and 22% (P = 0.04) respectively, for cefazolin 13% and 23% (P = 0.04), and for gentamicin 4% and 7% (P = 0.36). The resistance patterns for gram-negative bacteria for ciprofloxacin, cefazolin, and gentamicin were not significantly different in the two tested time periods (all P greater then 0.05).

Conclusions: There was increased resistance of gram-positive organisms to ciprofloxacin and cefazolin, but not gentamicin, in the two examined time periods. Increased resistance to these commonly used antibiotics emphasizes the need for close follow-up after initial empiric treatment, and maintaining a low threshold for selecting alternative therapy.

Liebert

Ciprofloxacin in primary prophylaxis of spontaneous bacterial peritonitis: A randomized, placebo-controlled study.

2008-03-06T06:55:00.000-08:00

Ciprofloxacin in primary prophylaxis of spontaneous bacterial peritonitis: A randomized, placebo-controlled study.

J Hepatol. 2008 Feb

Terg R, Fassio E, Guevara M, Cartier M, Longo C, Lucero R, Landeira C, Romero G, Dominguez N, Muñoz A, Levi D, Miguez C, Abecasis R.
Unidad de Hígado, Hospital de Gastroenterología “Dr. Bonorino Udaondo”, Sección Hepatología, Av. Caseros 2061, 1264 Buenos Aires, Argentina.

BACKGROUND/AIMS: Low protein concentration in ascitic fluid has been identified as a risk factor for spontaneous bacterial peritonitis (SBP). Until now, primary prophylaxis has not been recommended in these patients. The aim was to investigate the efficacy of long-term administration of ciprofloxacin to prevent SBP.

METHODS: One hundred cirrhotic patients with (less then) 1.5g/dl of total protein in ascitic fluid were randomized prospectively, in a double blind fashion to receive ciprofloxacin 500mg/day (n=50) or placebo (n=50) for 12 months.

RESULTS: Baseline data were similar in both groups. In the ciprofloxacin group, SBP occurred almost four times less frequently than in the placebo group but it was not statistically significant. The probability of survival at 12 months was significantly higher in patients receiving ciprofloxacin (86% versus 66%) (p<0.04). p="0.05).">

CONCLUSIONS: Patients with cirrhosis and low protein concentration in ascitic fluid are candidates to receive long-term prophylaxis to reduce the risk of infections and improve survival.

Elsevier

New British and American guidelines for the antibiotic prophylaxis of infective endocarditis: do the changes make sense? A critical review.

2008-03-05T21:14:00.000-08:00

New British and American guidelines for the antibiotic prophylaxis of infective endocarditis: do the changes make sense? A critical review.

Curr Opin Infect Dis. 2008 Apr

Shanson D.
Department of Medical Microbiology, Great Ormond Street Hospital for Children, London, UK.

PURPOSE OF REVIEW: The British Society for Antimicrobial Chemotherapy and the American Heart Association have radically revised their guidelines for the antibiotic prophylaxis of endocarditis. This review discusses the evidence behind the most controversial changes and considers possible future developments.

RECENT FINDINGS: The new guidelines emphasize good oral hygiene for preventing viridans streptococcal endocarditis. Antibiotic prophylaxis for dental procedures is only recommended for patients with the highest-risk cardiac conditions. American Heart Association guidelines no longer recommend prophylaxis for urological and gastrointestinal procedures.

SUMMARY: While only up to 6% of endocarditis cases may be prevented by antibiotic prophylaxis there is controversy as to what to recommend for the individual cardiac patient undergoing a given procedure. The new guidelines about dental prophylaxis are based on epidemiological studies that failed to include sufficient subjects undergoing specific interventions. When considering viridans streptococcal rather than total bacteraemia rates, asserting that the prevalence of bacteraemia after invasive dental procedures is similar to that after toothbrushing may be incorrect. The British Society for Antimicrobial Chemotherapy report probably overestimates the risk of fatal anaphylaxis after an oral dose of amoxicillin. In contrast, the American Heart Association guidelines comment on the absence of any reports of fatal anaphylaxis associated with the antibiotic prophylaxis of endocarditis.

Lippincott, Williams & Wilkins

Ciprofloxacin-Resistant Salmonella enterica Serotype Typhimurium, China

2008-03-02T18:45:00.000-08:00

Ciprofloxacin-Resistant Salmonella enterica Serotype Typhimurium, China

EID -Volume 14, Number 3–March 2008

Ciprofloxacin-Resistant Salmonella enterica Serotype Typhimurium, China
Shenghui Cui,* Jingyun Li,* Ziyong Sun,† Changqin Hu,* Shaohong Jin,* Yunchang Guo,‡ Lu Ran,‡ and Yue Ma* *State Food and Drug Administration, Beijing, People's Republic of China; †Huazhong University of Science and Technology, Wuhan, People's Republic of China; and ‡Chinese Center for Disease Control and Prevention, Beijing, People's Republic of China
Salmonellae are a common cause of community-acquired foodborne bacterial gastroenteritis worldwide. The incidence of Salmonella infections in the People's Republic of China has not been well documented. However, in the United States, ≈1.4 million persons are infected by Salmonella spp. each year (1). Although >2,500 serotypes have been reported, Salmonella enterica serotype Typhimurium is 1 of the leading serotypes causing salmonellosis worldwide (2). Fluoroquinolones such as ciprofloxacin are strongly recommended for treatment of severe S. Typhimurium infections in adults (3).

In this study, we characterized all S. Typhimurium isolates recovered from May 2002 through October 2005 from outpatients of Tongji Hospital, Wuhan, China, a sentinel hospital in the National Center for Surveillance of Antimicrobial Resistance. During the time of this study, Tongji Hospital strictly followed the recommendation for treatment of severe S. Typhimurium infections.

The Study

We analyzed stool samples from outpatients who came to Tongji Hospital from the local community for treatment of diarrhea during the study period. A total of 44 S. Typhimurium isolates were recovered from the samples. S. Typhimurium was identified by using standard biochemical tests and commercial typing antiserum (Statens Serum Institute, Copenhagen, Denmark) according to the manufacturer's instructions. MICs of 15 antimicrobial drugs (Table) were determined by using the broth-microdilution method; susceptibility to streptomycin was measured by using the disk-diffusion method as recommended by the Clinical and Laboratory Standards Institute (4). All isolates were further characterized by mutation analysis in the quinolone-resistance determining regions (QRDRs), pulsed-field gel electrophoresis (PFGE), and screening for class I integrons and β-lactamase genes as previously described (5–8).

Of the 44 isolates, 36 (82%) were resistant to nalidixic acid and 31 (70%) were resistant to ciprofloxacin (Table). Only 3 isolates, recovered in 2002, were susceptible to all 15 tested antimicrobial drugs; 36 (82%) displayed resistance to at least 8 drugs. Of 13 antimicrobial drug–resistant phenotypes identified, the most often observed phenotype (21/44) was resistance to amoxicillin–clavulanic acid, ampicillin, chloramphenicol, ciprofloxacin, gentamicin, nalidixic acid, sulfamethoxazole, streptomycin, trimethoprim–sulfamethoxazole, and tetracycline (R-type AcAmCCpGNSStSxtT). All isolates were susceptible to cefotaxime and ceftazidime; 5 isolates obtained in 2004 were intermediately susceptible to cefepime (MIC 16 μg/mL) (Appendix Figure).

Overall, 8 PFGE strain types (A–H) and 6 clusters (1–6) were identified. All isolates that belonged to clusters 1, 2, and 4 were resistant to ciprofloxacin and to 8–11 other antimicrobial drugs. Two dominant patterns, B and F, were identified and included 16 and 10 ciprofloxacin-resistant isolates, respectively. Among 16 isolates of pattern B, 14 isolates showed the R-type AcAmCCpGNSStSxtT, and 1 was additionally resistant to kanamycin. In pattern F, 4 isolates showed the R-type AcAmCCpGNSStSxtT, and 5 were additionally resistant to kanamycin.

Point mutations in the QRDR of gyrA, parC, or parE were identified in 35 of 36 nalidixic acid–resistant isolates, whereas no gyrB mutations and no qnr plasmid were found. For 5 nalidixic acid–resistant and ciprofloxacin low-level–resistant isolates, 4 isolates harbored single (D87N) or double (S83F, D87N) mutations in GyrA, and no mutation was found in 1 isolate (ST6). All 31 ciprofloxacin-resistant isolates accumulated a minimum of 3 mutations: GyrA(S83F, D87N), ParC(S80R) (28 isolates) or GyrA(S83F, D87G), ParC(S80R) (3 isolates). Two ciprofloxacin-resistant isolates with PFGE pattern C and 1 isolate with PFGE pattern A2 harbored an additional mutation in ParE (S458P) (Figure).

Of 39 sulfamethoxazole-resistant isolates encompassing PFGE clusters 1, 2, 3, and 4, 37 possessed class 1 integrons. All class 1 integron–positive isolates were resistant to 6–12 antimicrobial drugs; 2 distinct class 1 integrons were identified in 37 isolates. Of isolates obtained from 2002 through 2005, 32 contained a 1.9-kb integron gene cassette dhfrXII-orfF-aadA2. In 2004 and 2005, 3 and 2 isolates, respectively, contained a 2-kb integron gene cassette blaOXA-30-aadA1. None of the 36 ampicillin-resistant isolates contained TEM or SHV enzyme, but OXA-30 gene was detected in 32 isolates, identical in DNA sequence to GenBank AF255921. All 32 isolates harboring OXA-30 enzyme showed MICs to cefepime of 2–16 μg/mL, whereas isolates lacking OXA-30 showed MICs to cefepime of <1>.

Conclusions

We report a high incidence of fluoroquinolone-resistant S. Typhimurium isolates from Tongji Hospital outpatients. The MIC variation for ciprofloxacin differed 2- to 4-fold in isolates that had the same QRDR mutation profile, which implies that other mechanisms might partially contribute to the resistance phenotype (Appendix Figure).

After PFGE analysis, S. Typhimurium isolates were grouped into 3 ciprofloxacin-susceptible clusters and ciprofloxacin-resistant clusters. Similar distribution patterns have also been observed in isolates from Japan (9), which suggests a distinct genetic lineage for ciprofloxacin-resistant isolates that have become dominant. Studies have reported that ciprofloxacin-resistant S. Typhimurium isolates were usually resistant to multiple drugs (9,10). In this study, all ciprofloxacin-resistant S. Typhimurium isolates were resistant to 8–11 additional antimicrobial drugs. Among the 32 isolates harboring OXA-30 enzyme in this study, only 5 with PFGE pattern F showed intermediate resistance to cefepime, which suggests different levels of OXA gene expression or the contribution of other unknown mechanisms.

The high incidence of quinonlone-resistant S. Typhimurium isolates in this study might be affected by several factors. First, patients infected by antimicrobial drug–resistant S. Typhimurium strains had higher rates of hospitalization than did patients infected by susceptible strains (11,12), and the isolates in this study were from a university-affiliated medical center that usually treats patients with severe illness. Second, US studies have estimated that half of outpatient antimicrobial drugs were inappropriately prescribed for conditions such as viral illness (13). In China, inappropriate prescriptions might be even more common because antimicrobial drug prescriptions in hospitals are a source of profit. Although we do not have patient antimicrobial drug–use information, the easy access to antimicrobial drugs raises the possibility that outpatients might have taken fluoroquinolones after the onset of the illness but before the collection of stool specimens. Third, because livestock products are a common source of salmonellosis, the dissemination of ciprofloxacin-resistant S. Typhimurium might have been facilitated by the use of fluoroquinolones in livestock production (2). Last, use of other antimicrobial drugs, such as ampicillin, gentamicin, or streptomycin, may also contribute to the spreading of fluoroquinolone-resistant S. Typhimurium because all the ciprofloxacin-resistant isolates were also resistant to 8–11 additional antimicrobial drugs.

Although fluoroquinolone-resistant isolates were prevalent in Tongji Hospital, ciprofloxacin is still empirically used to treat salmonellosis in adults, due partly to the absence of systematic surveillance programs to actively monitor antimicrobial drug resistance in Salmonella spp. Because local data on antimicrobial drug susceptibility are less available, we strongly recommend that hospitals and national and local health laboratories develop and maintain the capacity to perform Salmonella culture and in vitro susceptibility testing.

Acknowledgments

We thank Patrick F. McDermott for revision and helpful comments on the manuscript.

This research was supported by grant (2005DIB3J159) from the Ministry of Science and Technology of the People's Republic of China.

Dr Cui is a microbiologist in the National Center for Surveillance of Antimicrobial Resistance, the State Food and Drug Administration, Beijing, China. His professional interests include developing detection methods for bacterial pathogens, molecular epidemiology, and antimicrobial drug–resistance mechanisms of bacterial pathogens.

References

Mead PS, Slutsker L, Dietz V, McCaig LF, Bresee JS, Shapiro C, et al. Food-related illness and death in the United States. Emerg Infect Dis. 1999;5:607–25.
Galanis E, Lo Fo Wong DM, Patrick ME, Binsztein N, Cieslik A, Chalermchikit T, et al. Web-based surveillance and global Salmonella distribution, 2000–2002. Emerg Infect Dis. 2006;12:381–8.
Guerrant RL, Van Gilder T, Steiner TS, Thielman NM, Slutsker L, Tauxe RV, et al. Practice guidelines for the management of infectious diarrhea. Clin Infect Dis. 2001;32:331–51.
Clinical and Laboratory Standards Institute. Performance standards for antimicrobial susceptibility testing; seventeenth informational supplement. Wayne (PA): The Institute; 2007 (document M100-S17).
Barrett TJ, Gerner-Smidt P, Swaminathan B. Interpretation of pulsed-field gel electrophoresis patterns in foodborne disease investigations and surveillance. Foodborne Pathog Dis. 2006;3:20–31.
Giraud E, Brisabois A, Martel JL, Chaslus-Dancla E. Comparative studies of mutations in animal isolates and experimental in vitro– and in vivo–selected mutants of Salmonella spp. suggest a counterselection of highly fluoroquinolone-resistant strains in the field. Antimicrob Agents Chemother. 1999;43:2131–7.
Levesque C, Piche L, Larose C, Roy PH. PCR mapping of integrons reveals several novel combinations of resistance genes. Antimicrob Agents Chemother. 1995;39:185–91.
Ouellette M, Bissonnette L, Roy PH. Precise insertion of antibiotic resistance determinants into Tn21-like transposons: nucleotide sequence of the OXA-1 beta-lactamase gene. Proc Natl Acad Sci U S A. 1987;84:7378–82.
Izumiya H, Mori K, Kurazono T, Yamaguchi M, Higashide M, Konishi N, et al. Characterization of isolates of Salmonella enterica serovar Typhimurium displaying high-level fluoroquinolone resistance in Japan. J Clin Microbiol. 2005;43:5074–9.
Hakanen A, Kotilainen P, Huovinen P, Helenius H, Siitonen A. Reduced fluoroquinolone susceptibility in Salmonella enterica serotypes in travelers returning from Southeast Asia. Emerg Infect Dis. 2001;7:996–1003.
Varma JK, Molbak K, Barrett TJ, Beebe JL, Jones TF, Rabatsky-Ehr T, et al. Antimicrobial-resistant nontyphoidal Salmonella is associated with excess bloodstream infections and hospitalizations. J Infect Dis. 2005;191:554–61.
Martin LJ, Fyfe M, Dore K, Buxton JA, Pollari F, Henry B, et al. Increased burden of illness associated with antimicrobial-resistant Salmonella enterica serotype Typhimurium infections. J Infect Dis. 2004;189:377–84.
Nyquist AC, Gonzales R, Steiner JF, Sande MA. Antibiotic prescribing for children with colds, upper respiratory tract infections, and bronchitis. JAMA. 1998;279:875–7.

CDC

Intracameral antibiotics: Questions for the United States based on prospective studies

2008-03-01T19:10:00.000-08:00

Intracameral antibiotics: Questions for the United States based on prospective studies

J Cataract Refract Surg. 2008 Mar

Liesegang TJ.
From the Mayo Clinic, Jacksonville, Florida, USA.

Recent prospective studies from Europe suggest the use of intracameral antibiotics for prophylaxis of endophthalmitis, although the studies did not make a comparison with the most common United States prophylaxis techniques. Thus, the European studies as well as the present literature were reviewed in an attempt to place the European studies in perspective with regard to the present U.S. protocol and the available literature. There is no worldwide-established approach to prophylaxis of endophthalmitis. In the absence of a strong evidence-based approach most surgeons use surrogate studies to support their techniques and mold their opinions based on their interpretation of the literature and when they believe organisms causing endophthalmitis enter the eye. The review showed that preoperative topical antibiotics limit the number of bacteria on the ocular surface at surgery and postoperative topical antibiotics are most appropriate to address postoperative inoculation until the wound is sealed (with no tapering). Whereas intracameral antibiotic injection may be an appropriate route of administration to address inoculation occurring at the time of surgery, more research on safety and effectiveness is needed before we expose the millions of eyes having cataract surgery each year. A multipronged approach to limit endophthalmitis risk is also needed, with antibiotics as only part of the strategy.

Elsevier

Antimicrobials as a contributory factor in oral candidosis - a brief overview

2008-03-01T19:05:00.000-08:00

Antimicrobials as a contributory factor in oral candidosis - a brief overview

Oral Dis. 2008 Mar

Soysa NS, Samaranayake LP, Ellepola AN.
Division of Pharmacology, Department of Oral Medicine and Periodontology, Faculty of Dental Sciences, University of Peradeniya, Peradeniya, Sri Lanka; 2Oral Bio-Sciences, Faculty of Dentistry, University of Hong Kong, Hong Kong; 3Department of Bioclinical Sciences, Faculty of Dentistry, Health Sciences Center, Kuwait University, Kuwait

Dr NS Soysa, Division of Pharmacology, Department of Oral Medicine and Periodontology, Faculty of Dental Sciences, University of Peradeniya, Peradeniya, Sri Lanka. Tel: 94-81-2387500, Fax: 94-81-2388948, E-mail: niroshanis@pdn.ac.lk/hnsnit@yahoo.com

The advent of the human immunodeficiency virus infection and the increasing prevalence of compromised individuals in the community due to modern therapeutic advances have resulted in a resurgence of opportunistic infections, including oral candidosis, which is by far the most common oral fungal infection in man. Broad-spectrum antibiotics used in the treatment of a wide range of disease conditions have also been attributed as a predisposing factor of oral candidosis. In this mini review we discuss the research findings on the relationship between antibiotics and oral candidosis and possible mechanisms of pathogenicity following such therapy.

Blackwell Synergy