Monday, December 24, 2007

Optimizing Therapy for Stenotrophomonas maltophilia.

Optimizing Therapy for Stenotrophomonas maltophilia.
Semin Respir Crit Care Med. 2007 Dec
Muder RR.

Infectious Disease Section, VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania.

STENOTROPHOMONAS (XANTHOMONAS) MALTOPHILIA is a nonfermentative, gram-negative bacillus that is widely distributed in natural and humanmade environments. In the nonhospital setting it is an uncommon pathogen, typically causing soft tissue infection of contaminated wounds. In the hospital setting, particularly among critical care and oncology patients, S. MALTOPHILIA may cause catheter-related bacteremia, pneumonia, soft tissue infection, meningitis, prosthetic valve endocarditis, and ocular infections. S. MALTOPHILIA is usually resistant to multiple antimicrobials, including expanded-spectrum penicillins, third-generation cephalosporins, carbapenems, aminoglycosides, and quinolones. Trimethoprim-sulfamethoxazole is the antimicrobial agent of choice for this pathogen but is bacteriostatic. Further, resistance to this agent is increasing. Certain combinations of antibiotics are synergistic and may be appropriate for patients harboring resistant organisms or with life-threatening infections.

Thieme Connect

Optimizing Use of beta-Lactam Antibiotics in the Critically Ill.

Optimizing Use of beta-Lactam Antibiotics in the Critically Ill.
Semin Respir Crit Care Med. 2007 Dec
Roberts JA, Lipman J.

Burns Trauma and Critical Care Research Centre, University of Queensland, Brisbane, Australia.

The escalation of serious infections in critically ill patients over the past 25 years has continued despite advances in contemporary medicine. Ongoing research to reduce the high morbidity and mortality rates is mandated. beta-lactam antibiotics are often used empirically in serious infections. The efficacy of these time-dependent antibiotics is correlated with the time that concentrations are maintained above the minimum inhibitory concentration of the infective pathogen. In critically ill patients, pathophysiological changes can reduce antibiotic concentrations and thus alternative modes of administration such as continuous infusion have been studied and shown to standardize beta-lactam pharmacokinetics and meet pharmacodynamic targets. Clinical data supporting the efficacy of continuous infusion are currently scarce, but data continue to grow. Likewise antibiotic resistance continues to grow. Recent data suggest that poor dosing strategies may be contributing to this problem, which is exacerbated by a lack of development of alternate antibiotics. Suffice to say clinicians must use antibiotic regimens that optimally treat the individual patient and reduce the development of antibiotic resistance.

Thieme Connect

Optimizing Therapy for Infections Caused by Enterobacteriaceae Producing Extended-Spectrum beta-Lactamases.

Optimizing Therapy for Infections Caused by Enterobacteriaceae Producing Extended-Spectrum beta-Lactamases.

Semin Respir Crit Care Med. 2007 Dec

Endimiani A, Paterson DL.

Division of Infectious Diseases, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.

The spread of multidrug-resistant Enterobacteriaceae is complicating the treatment of nosocomial infections. In many parts of the world, resistance to third-generation cephalosporins exceeds 10% of total nosocomial isolates and 30% of isolates detected in the intensive care unit. This resistance is frequently due to the acquisition of plasmids containing genes encoding for extended-spectrum beta-lactamases (ESBLs). Furthermore, these mobile elements often carry genes encoding resistance to other drugs such as aminoglycosides. A high risk of poor clinical outcome has been observed in patients infected with ESBL producers receiving third-generation cephalosporins, even if the organism appears susceptible to the antibiotic. For this reason, clinical microbiology laboratories are advised to incorporate specific ESBL detection methodology into routine clinical practice. This should prevent erroneous use of cephalosporins for these infections. Most ESBL producers remain susceptible to carbapenems, and these agents are considered the drugs of choice against ESBL-producing organisms. Unfortunately, there is now an increasing occurrence of carbapenem resistance in the Enterobacteriaceae. In this context, clinical response to new antibiotics (e.g., tigecycline) and old antibiotics (e.g., colistin) with good in vitro activity against ESBL producers needs to be evaluated.

Thieme Connect

Optimizing use of colistin and polymyxin B in the critically ill.

Optimizing use of colistin and polymyxin B in the critically ill.

Semin Respir Crit Care Med. 2007 Dec

Nation RL, Li J.
Facility for Anti-Infective Drug Development and Innovation, Victorian College of Pharmacy, Monash University, Parkville, Victoria, Australia.

Polymyxin B and colistin are being used increasingly for the treatment of infections caused by gram-negative bacteria that are resistant to all other currently available antibiotics. Although the polymyxins have been available in the clinic for around 50 years, they have never been subjected to the drug development procedures required of modern pharmaceuticals. As a result, the available knowledge on the pharmacokinetics (PK), pharmacodynamics (PD), and toxicodynamics (TD) of the polymyxins is limited. Although significant advances have been made in the last 5 years or so, there are still large gaps in our understanding of the PK, PD, and TD, and of the PK/PD and PK/TD relationships. This information is required to generate recommendations on dosage regimens for various categories of critically ill patients. This paper reviews the growing understanding of the pharmacology of the polymyxins and factors that may impact on the optimization of the dose of these antibiotics in critically ill patients.

Thieme Connect

Optimizing antipseudomonal therapy in critical care

Optimizing antipseudomonal therapy in critical care

Iredell JR.
Centre for Infectious Diseases and Microbiology, University of Sydney/Westmead Hospital, Westmead, Australia.

PSEUDOMONAS AERUGINOSA is a common and important pathogen in the critically ill. It combines environmental hardiness with genomic plasticity and is well adapted to the various niches available in the intensive care unit (ICU). Unresolved arguments over the value of dual versus monotherapy relate primarily to rapidity of killing and to the avoidance of therapeutic failure due to antibiotic resistance. Increasing resistance to conventional antibiotics means that we need to be aware of the factors that promote the success of this pathogen in the ICU, and of emerging alternative strategies. This review focuses on an understanding of the underlying issues and on the practical aspects of prescribing, particularly in the ICU.

Thieme Connect

Friday, December 21, 2007

Optimizing Therapy for Vancomycin-Resistant Enterococci (VRE).

Optimizing Therapy for Vancomycin-Resistant Enterococci (VRE).
Semin Respir Crit Care Med. 2007 Dec

Linden PK.
Department of Critical Care Medicine, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.

Enterococci are gram-positive, facultative bacteria with low intrinsic virulence but capable of causing a diverse variety of infections such as bacteremia with or without endocarditis, and intra-abdominal, wound, and genitourinary infection. During the past 2 decades the incidence of hospital-acquired enterococcal infection has significantly risen and is increasingly due to multidrug-resistant strains, primarily to the coacquisition of genetic determinants that encode for the stable expression of high-level beta-lactam, aminoglycoside, and glycopeptide resistance. Because enterococci constitute part of the normal colonizing flora, careful clinical interpretation of cultures that grow enterococci is paramount to avoid unnecessary and potentially deleterious antimicrobial therapy. Traditional antimicrobial treatment for ampicillin- and glycopeptide-susceptible enterococcal infection remains a penicillin-, ampicillin-, semisynthetic penicillin-based regimen, or vancomycin in a penicillin-intolerant individual. The need for a bactericidal combination with a cell-wall active agent combined with an aminoglycoside is most supported for native- or prosthetic valve endocarditis but is unproven for the majority of infections due to enterococci. The emergence of vancomycin-resistant enterococci prompted the clinical development of several novel and modified antimicrobial compounds approved for VRE infection (quinupristin-dalfopristin, linezolid) and several approved for non-VRE indications (daptomycin, tigecycline). There is a paucity of comparative clinical trial data with these new agents, although linezolid, based upon its efficacy and tolerability, appears to be the cornerstone of current treatment approaches. Despite a relatively short period of clinical use, enterococcal resistance has now been described for quinupristin-dalfopristin and linezolid and more recently even for daptomycin and tigecycline. Moreover, the optimal treatment of endocarditis due to VRE strains is unknown because, with the exception of daptomycin, current treatment options only yield bacteriostasis. Nonantimicrobial measures to treat VRE infection, such as foreign body removal and percutaneous or surgical drainage of close-spaced infection, reduce both the need for and the duration of anti-enterococcal treatment and the emergence of resistance to the newer antimicrobials.

PMID: 18095227 [PubMed - in process]

Perioperative antibiotics and anti-inflammatory agents in cataract surgery.

Perioperative antibiotics and anti-inflammatory agents in cataract surgery.

Curr Opin Ophthalmol. 2008 Jan

Decroos FC, Afshari NA.
Duke University Eye Center, Duke University Medical Center, Durham, North Carolina, USA.

PURPOSE OF REVIEW: Cataract surgery has benefited from great technical advances but no consensus exists as regards optimal perioperative medical management of inflammation and infection prophylaxis.

RECENT FINDINGS: The present article primarily reviews recent evidence about the most advantageous antibiotic regimen to minimize endophthalmitis, and the utility of steroids or nonsteroidal anti-inflammatory drugs (NSAIDs) in management of both postoperative inflammation and cystoid macular edema. Prospective data from Europe supports the efficacy of intracameral cephalosporins in reducing the incidence of endophthalmitis. We compare this with retrospective data from the United States describing a low incidence of endophthalmitis when using fourth-generation fluoroquinolones as chemoprophylaxis. Other studies demonstrate the anti-inflammatory effect of multiple perioperative topical NSAIDs. Further important questions remain, however, including whether NSAIDs exhibit a superior side-effect profile relative to corticosteroids, whether benefit exists to combination NSAID/corticosteroid therapy, as well as whether NSAIDS can reduce the incidence of cystoid macular edema.

SUMMARY: New evidence clarifies the use of intracameral antibiotics, and other studies support a niche anti-inflammatory role for NSAIDs.

PMID: 18090893 [PubMed - in process]

The role of NSAIDs in the management of postoperative ophthalmic inflammation.

Drugs. 2007

Colin J.

University Hospital Complex of Bordeaux, Peflegrin Hospital, Bordeaux, France.

Recent advances in cataract surgery, such as phacoemulsification, small-incision surgery and advances in foldable intraocular lenses, have resulted in the decrease of physical trauma associated with cataract surgery. The decrease in the physical surgical trauma decreases the release of prostaglandins, which are the main players in postoperative ocular inflammation. However, postoperative inflammation continues to be a cause of patient discomfort, delayed recovery and, in some cases, suboptimal visual results. Left untreated, this inflammation might interfere with patients' rehabilitation and/or contribute to the development of other complications, such as cystoid macular oedema.NSAIDs are commercially available, in topical or systemic formulations, for the prophylaxis and treatment of ocular conditions. Topically applied NSAIDs are commonly used in the management and prevention of non-infectious ocular inflammation and cystoid macular oedema following cataract surgery. They are also used in the management of pain following refractive surgery and in the treatment of allergic conjunctivitis. Despite their chemical heterogeneity, all NSAIDs share the similar therapeutic property of inhibiting the cyclo-oxygenase enzyme. The appeal of using NSAIDs in the treatment of ocular inflammation hinges on the complications associated with corticosteroids, the other commonly used therapy for ophthalmic inflammation.

PMID: 17547472 [PubMed - indexed for MEDLINE]

Saturday, December 15, 2007

Carbapenems: a potent class of antibiotics.

Carbapenems: a potent class of antibiotics.
Expert Opin Pharmacother. 2008 Jan

Nicolau DP.
Hartford Hospital, Center for Anti-Infective Research and Development, 80 Seymour Street, Hartford, Connecticut 06102-5037, USA +1 860 545 3941 ; +1 860 545 3992 ;

The purpose of this review is to assess the relative strengths and weaknesses of individual members of the carbapenem class of antibiotics. Clinical trials and review articles were identified from a Medline search (1979 - July 2006), in addition to, reference citations from identified publications, abstracts from the Interscience Conferences on Antimicrobial Agents and Chemotherapy and the 12th International Congress on Infectious Disease, and package inserts. Articles in English were reviewed, with emphasis on those containing efficacy or safety data. Carbapenems bind to critical penicillin-binding proteins, disrupting the growth and structural integrity of bacterial cell walls. They provide enhanced anaerobic and Gram-negative coverage as compared with other beta-lactams and their stability against extended-spectrum beta-lactamases (ESBLs) makes them an effective treatment option. The most common adverse effects are infusion-site complications and gastrointestinal distress.

Ertapenem has limited efficacy against non-fermenting, Gram-negative bacteria, restricting its use to community-acquired infections. Imipenem is slightly more effective against Gram-positive organisms and meropenem slightly more effective against Gram-negative organisms. However, both have broad-spectrum activity, including non-fermenting, Gram-negative bacteria. Among non-fermenting, Gram-negatives, resistance to imipenem in particular is increasing. Doripenem is in late-stage clinical development and combines the broad-spectrum coverage of imipenem and meropenem, and more potent activity against Pseudomonas aeruginosa. Due to the increasing challenges represented by ESBLs and multi-drug resistant organisms, the carbapenems are assuming a greater role in the treatment of serious infections.

Imipenem and meropenem are presently available and have been shown to be effective against nosocomial infections.

Doripenem is an investigational carbapenem that has completed Phase III clinical trials and that has the potential to improve on this efficacy and minimize the emergence of resistance to the carbapenem class.

PMID: 18076336 [PubMed - in process]

Friday, November 30, 2007

National trends in emergency department antibiotic prescribing for children with acute otitis media, 1996 2005.

National trends in emergency department antibiotic prescribing for children with acute otitis media, 1996 2005.

Acad Emerg Med. 2007 Dec

Fischer T, Singer AJ, Lee C, Thode HC Jr.
Department of Emergency Medicine, Stony Brook University Medical Center, Stony Brook, NY, USA.

OBJECTIVES: Withholding antibiotics in nontoxic children with acute otitis media (AOM) is now recommended to reduce bacterial resistance rates. Using the National Hospital Ambulatory Medical Care Survey (NHAMCS), the authors describe the national trends for prescribing antibiotics in children with AOM presenting to emergency departments (EDs) in the United States over the past decade. The authors hypothesized that the rates of prescribing antibiotics would decline over time.

METHODS: This was a retrospective study of NHAMCS databases. A national sampling of ED visits for 1996-2005 was used to identify trends in ED prescription of antibiotics to patients with AOM. The National Drug Code Directory Drug Classes were used to identify type of antibiotic prescribed. Frequency and type of antibiotic prescription patterns over time were evaluated.

RESULTS: There were 2.6 million and 2.1 million ED visits for AOM during the first and last years of the study. Children ages 2-12 years accounted for about 40% of all ED visits for AOM, with another 40% in the younger than 2 years age group and 20% in the older than 12 years of age group. During the first and last year of the study, 79.2% and 91.3% of the patients with AOM were prescribed antibiotics, respectively. There was a slight increasing trend in the proportion prescribed antibiotics over time (p = 0.02). The rates of use of antibiotics for AOM were similar in all three age groups.

CONCLUSIONS: There was a slight increase in the percentage of children with AOM who were prescribed antibiotics in the ED between 1996 and 2005. There was also no change in the patterns of prescribing antibiotics.

PMID: 18045893 [PubMed - in process]

Thursday, November 22, 2007

Speed of bacterial kill with a fluoroquinolone compared with nonfluoroquinolones: clinical implications and a review of kinetics of kill studies.

Speed of bacterial kill with a fluoroquinolone compared with nonfluoroquinolones: clinical implications and a review of kinetics of kill studies.
Adv Ther. 2007 Sep-Oct

Lichtenstein SJ, Wagner RS, Jamison T, Bell B, Stroman DW.
Associate Clinical Professor of Pediatrics and Surgery, University of Illinois College of Medicine at Peoria and Chicago, Illinois Eye Center, Peoria, Illinois.

It is important to rapidly eradicate bacteria in patients with bacterial conjunctivitis in order to decrease disease transmission, shorten symptom duration, and minimize the emergence of resistant bacteria. This paper presents the results of kinetics of kill studies on 3 commonly isolated pathogens in bacterial conjunctivitis.

A more rapid speed of kill with moxifloxacin compared with other nonfluoroquinolone antibiotics (tobramycin, gentamicin, polymyxin B/trimethoprim, or azithromycin) was observed in Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae infections. Moxifloxacin achieved a 99.9% kill at approximately 1 h for S aureus, 2 h for S pneumoniae, and 30 min for H influenzae.

In comparison, other nonfluoroquinolone therapies took longer to achieve a bactericidal (3-log) kill and some demonstrated no change or an increase in bacterial growth. Based on these findings, it is concluded that moxifloxacin kills bacteria more rapidly than nonfluoroquinolone topical ocular antibiotics.

PMID: 18029337 [PubMed - in process]

Thursday, November 15, 2007

Telavancin: A novel lipoglycopeptide antimicrobial agent.

Telavancin: A novel lipoglycopeptide antimicrobial agent

Ryan J. Attwood and Kerry L. LaPlante

RYAN J. ATTWOOD, PHARM.D., is Postgraduate Year 1 Pharmacy Resident, Henry Ford Hospital, Detroit, MI; at the time of writing he was Pharm.D. degree candidate, University of Rhode Island, Providence. KERRY L. LAPLANTE, PHARM.D., is Assistant Professor of Pharmacy, Department of Pharmacy Practice, University of Rhode Island, Veterans Affairs Medical Center, Providence.

Address correspondence to Dr. LaPlante at the Department of Pharmacy Practice, University of Rhode Island, Veterans Affairs Medical Center (151), Research Building, 830 Chalkstone Avenue, Providence, RI 02908 (


The pharmacology, activity, pharmacokinetics, pharmacodynamics, clinical efficacy, safety, dosage, and place in therapy of telavancin are reviewed.


Telavancin is a lipoglycopeptide antimicrobial agent under development for use in the treatment of multidrug-resistant gram-positive infections. Telavancin, like vancomycin, inhibits cell-wall biosynthesis by binding to late-stage cell-wall precursors. However, unlike vancomycin, telavancin also depolarizes the bacterial cell membrane and disrupts its functional integrity.

Telavancin has concentration-dependent bactericidal activity and is active against gram-positive aerobic and anaerobic organisms. It is highly protein bound (93%) and has a volume of distribution of 115 mL/kg and a half-life of approximately eight hours. Telavancin is eliminated renally, and a dosage reduction is required in renally impaired patients. Animal models suggest that telavancin may be effective in the treatment of soft-tissue infections, bacteremia, endocarditis, meningitis, and pneumonia caused by gram-positive pathogens. Telavancin was not inferior to standard treatment for complicated skin and soft-tissue infections in two Phase II clinical trials and two Phase III clinical trials.

A new drug application has been submitted for this indication, and Phase III trials to evaluate use in hospital-acquired-pneumonia, including infections caused by methicillin-resistant Staphylococcus aureus (MRSA), are planned. Adverse effects include metallic taste, nausea, vomiting, headache, foamy urine, Q-Tc-interval prolongation, hypokalemia, and serum creatinine increases. In trials evaluating telavancin for skin and soft-tissue infections, the dosage was 10 mg/kg i.v. once daily.


Telavancin is a promising new agent for gram-positive infections and may offer an alternative to vancomycin for MRSA-associated infections.

American Journal of Health-System Pharmacy

Saturday, November 10, 2007

Daptomycin in the Treatment of Bacteremia

Daptomycin in the Treatment of Bacteremia
George Sakoulas MDa, Yoav Golan MD, MSb, Kenneth C. Lamp PharmDc, , , Lawrence V. Friedrich PharmDc and Rene Russo PharmDc aNew York Medical College, Valhalla, New York, USAbTufts New England Medical Center, Boston, Massachusetts, USAcCubist Pharmaceuticals, Inc., Lexington, Massachusetts, USA. Available online 28 September 2007.


The aim of this study was to describe the clinical experience with daptomycin in the treatment of bacteremia. Patients with a diagnosis of catheter-related or non–catheter-related bacteremia and no other concurrent infection were identified from the Cubicin Outcomes Registry and Experience (CORE) 2004. Treatment success was determined by investigators using protocol criteria and defined as cure or improvement. Of 168 patients with bacteremia, 126 were clinically evaluable. Of those, 52 (41%) patients were aged ≥66 years, 54 (43%) received daptomycin in an intensive care unit, and 25 (20%) had chronic renal failure. The most common pathogens isolated were methicillin-resistant Staphylococcus aureus (33%), vancomycin-resistant enterococci (30%), and coagulase-negative staphylococci (30%). Of 126 patients, 86% received daptomycin after previous antibiotic therapy and most (69%) received concomitant antibiotics with daptomycin. Daptomycin therapy was started at a median dose of 4.0 mg/kg (range, 2.5 to 9.2 mg/kg). Daptomycin therapy had an overall clinical success rate of 89%. Clinical success was independent of baseline renal function, daptomycin dose, pathogen, first-line use, or concomitant antibiotic therapy. These results support the findings of a recent study in which daptomycin was demonstrated to be an effective option in the treatment of S aureus bacteremia. Data in the current study provide insight into the clinical experience using daptomycin to treat bacteremia caused by other gram-positive pathogens. Given the limitations of retrospective studies and lack of follow-up data, additional studies are needed to make definitive evaluations with these pathogens.

Science Direct

Wednesday, November 07, 2007

Goniothalamus species: a source of drugs for the treatment of cancers and bacterial infections?

Goniothalamus species: a source of drugs for the treatment of cancers and bacterial infections?
Evid Based Complement Alternat Med. 2007 Sep

Wiart C.
School of Pharmacy, The University of Nottingham (Malaysia Campus), Jalan Broga, 43500 Semenyih, Selangor, Malaysia.

Keywords: acetogenins, antibacterial, antifungal, apoptosis, cytotoxic, foodborn bacteria, Goniothalamus, Goniothalamus scortechinii, nosocomial, styryl-lactones.

Irrespective of the presence of cytotoxic acetogenins and styryl-lactones in the genus Goniothalamus, only 22 species in the genus Goniothalamus, out of 160 species (13.7%) have so far been investigated. In an effort to promote further research on the genus Goniothalamus which could represent a source of drugs for the treatment of cancers and bacterial infections, this work offers a broad analysis of current knowledge on Goniothalamus species. Therefore, it includes (i) taxonomy (ii) botanical description (iii) traditional medicinal uses and (iv) phytochemical and pharmacological studies. We discuss the molecular mechanisms of actions of acetogenins and styryl-lactones, with some emphasis on the possible involvement of protein kinase, Bax and TRAIL receptors in the cytotoxic effects of styryl-lactones. We also report (v) the growth inhibition of several nosocomial bacteria by Goniothalamus. scortechinii. The crude methanol extract of G. scortechinii showed a good and broad spectrum of antibacterial activity against both Gram-negative and Gram-positive bacteria.

Full Text Article

Evidence-based Complementary and Alternative Medicine

Biodegradable gentamicin delivery systems for parenteral use for the treatment of intracellular bacterial infections

Biodegradable gentamicin delivery systems for parenteral use for the treatment of intracellular bacterial infections

November 2007, Vol. 4, No. 6, Pages 677-688

Carlos Gamazo‌1 PhD, Biology, Full Professor of Microbiology, Vice Chairman of Department Council of Microbiology, Sandra Prior‌1 PhD, Pharmacy, María Concepción Lecároz‌1 PhD, Pharmacy, Ana Isabel Vitas‌1 PhD, Biology, Associate Professor of Microbiology, Miguel Angel Campanero‌2 PhD, Pharmacy, Associate Professor of Pharmacology, Guiomar Pérez‌2,3, Master in Science, Biology, David Gonzalez‌3 PhD, Biology, Associate Professor of Microbiology & María Jose Blanco-Prieto‌3 PhD, Pharmacy, Research Scientist, Associate Professor of Pharmaceutical Technology

1University of Navarra, Department of Microbiology, 31080 Pamplona, Spain +34 948 425 688; +34 948 425 649;

2Clínica Universitaria, Department of Clinical Pharmacology, 31080 Pamplona, Spain
3University of Navarra, Department of Pharmacy and Pharmaceutical Technology, 31080 Pamplona, Spain
† Author for correspondence

Gentamicin is an aminoglycoside with a wide spectrum of antibacterial activity. However, as a highly water-soluble drug, it penetrates cells poorly. This constitutes a particularly important drawback for treating intracellular bacterial infections. This major hurdle may be solved by the use of vectors to deliver and target bioactive agents to the intracellular sites of infection. Thus, in the case of antimicrobials, drug delivery systems may help to increase their therapeutic index in intracellular locations. The development and evolution of pharmaceutical forms of gentamicin for the parenteral treatment of intracellular pathogens is reviewed in this paper.

Expert Opinion

Monday, November 05, 2007

Xenorhabdus antibiotics: a comparative analysis and potential utility for controlling mastitis caused by bacteria

Xenorhabdus antibiotics: a comparative analysis and potential utility for controlling mastitis caused by bacteria

J Appl Microbiol. 2007 Nov 1

Furgani G, Böszörményi E, Fodor A, Máthé-Fodor A, Forst S, Hogan JS, Katona Z, Klein MG, Stackebrandt E, Szentirmai A, Sztaricskai F, Wolf SL.

Department of Genetics, Faculty of Natural Sciences, Eötvös University, Budapest, Hungary.

Aims: The role of antibiotics produced by bacterial symbionts of entomopathogenic nematodes is to suppress growth of microbes in the soil environment. These antibiotics are active against Gram-positive and Gram-negative bacteria, and were tested against mastitis isolates from dairy cows.

Methods and Results: Two bioassays were adapted for Xenorhabdus antibiotics; an overlay method on agar plates, and serially diluted, cell-free, Xenorhabdus cultures. The antimicrobial activities of the liquid cultures of 13 strains from five Xenorhabdus species were further evaluated. Antimicrobial activities of the type strains of X. nematophila, X. budapestensis and X. szentirmaii were tested on mastitis isolates of Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae with both bioassays. A previously reported antibiotic from X. nematophila, nematophin, was synthesized in three steps from tryptamine and 4-methyl-2-oxovaleric acid sodium salt.

Conclusions: The antibiotics of all three Xenorhabdus strains were powerful in either bioassay, but the sensitivity of the isolates differed from each other. While Kl. pneumoniae was the least susceptible, Staph. aureus had the highest sensitivity to each Xenorhabdus strain. Xenorhabdus szentirmaii and X. budapestensis were more potent antibiotic producers than X. nematophila, and raceme nematophin was ineffective against all mastitis isolates.

Significance and Impact of the Study: These results indicate that Xenorhabdus antibiotics are effective against mastitis isolates and should be further evaluated for their potential in mastitis control or prevention.

PMID: 17976177 [PubMed - as supplied by publisher]

Friday, November 02, 2007

Antibiotic resistant Staphylococcus aureus: a paradigm of adaptive power.

Antibiotic resistant Staphylococcus aureus: a paradigm of adaptive power.

Curr Opin Microbiol. 2007 Oct 5

de Lencastre H, Oliveira D, Tomasz A.

Laboratory of Microbiology, The Rockefeller University, 1230 York Avenue, New York, NY 10065, USA; Laboratory of Molecular Genetics, Instituto de Tecnologia Química e Biológica (ITQB) da Universidade Nova de Lisboa (UNL), 2780 Oeiras, Portugal.

Nothing documents better the spectacular adaptive capacity of Staphylococcus aureus than the response of this important human and animal pathogen to the introduction of antimicrobial agents into the clinical environment. The effectiveness of penicillin introduced in the early 1940s was virtually annulled within a decade because of the plasmid epidemics that spread the ss-lactamase gene through the entire species of S. aureus. In 1960 within one to two years of the introduction of penicillinase resistant ss-lactams (methicillin), methicillin resistant S. aureus (MRSA) strains were identified in clinical specimens. By the 1980s, epidemic clones of MRSA acquired multidrug resistant traits and spread worldwide to become one of the most important causative agents of hospital acquired infections. In the early 2000s, MRSA strains carrying the Tn1546 transposon-based enterococcal vancomycin resistant mechanism were identified in clinical specimens, bringing the specter of a totally resistant bacterial pathogen closer to reality. Then, in the late 1990s, just as effective hygienic and antibiotic use policies managed to bring down the frequency of MRSA in hospitals of several countries, MRSA strains began to show up in the community.

PMID: 17921044 [PubMed - as supplied by publisher]

Thursday, November 01, 2007

Reducing antibiotic overuse: a call for a national performance measure for not treating asymptomatic bacteriuria.

Reducing antibiotic overuse: a call for a national performance measure for not treating asymptomatic bacteriuria.

Clin Infect Dis. 2007 Nov

Gross PA, Patel B.
Department of Medicine, Hackensack University Medical Center, Hackensack, NJ 07601, USA.

Positive urinary tract culture results often represent asymptomatic bacteriuria, which does not need to be treated with antimicrobial agents. Avoiding treatment of asymptomatic bacteriuria in adults should reduce the risk of development of antibiotic resistance and is consistent with the Infectious Diseases Society of America and US Preventive Services Task Force guidelines on bacteriuria. A similar approach for not treating upper respiratory illnesses with antibiotics was initiated by the Centers for Disease Control and Prevention. We propose that a hospital and ambulatory performance measure should be developed for not treating asymptomatic bacteriuria in adults. In addition, such an effort would aid hospitals in confronting the proposal of the Centers for Medicare and Medicaid Services (to be implemented in 2009) to not pay the expenses associated with catheter-associated urinary tract infection.

University of Chicago Press

Monday, October 22, 2007

Protective effect of antibiotics against serious complications of common respiratory tract infections: retrospective cohort study with the UK General

Protective effect of antibiotics against serious complications of common respiratory tract infections: retrospective cohort study with the UK General Practice Research Database.

BMJ. 2007 Oct 18

Petersen I, Johnson AM, Islam A, Duckworth G, Livermore DM, Hayward AC.
UCL Centre for Infectious Disease Epidemiology, Department of Primary Care and Population Sciences, University College London, London NW3 2PQ.

OBJECTIVE: To determine the extent to which antibiotics reduce the risk of serious complications after common respiratory tract infections.

DESIGN: Retrospective cohort study.

SETTING: UK primary care practices contributing to the general practice research database. Data source 3.36 million episodes of respiratory tract infection.

MAIN OUTCOME MEASURES: Risk of serious complications in treated and untreated patients in the month after diagnosis: mastoiditis after otitis media, quinsy after sore throat, and pneumonia after upper respiratory tract infection and chest infection. Number of patients needed to treat to prevent one complication.

RESULTS: Serious complications were rare after upper respiratory tract infections, sore throat, and otitis media, and the number needed to treat was over 4000. The risk of pneumonia after chest infection was high, particularly in elderly people, and was substantially reduced by antibiotic use, with a number needed to treat of 39 for those aged >/=65 and 96-119 in younger age groups.

CONCLUSION: Antibiotics are not justified to reduce the risk of serious complications for upper respiratory tract infection, sore throat, or otitis media. Antibiotics substantially reduce the risk of pneumonia after chest infection, particularly in elderly people in whom the risk is highest.

Full text available:

British Medical Journal

Monday, October 08, 2007

Effects of tigecycline, linezolid and vancomycin on biofilms of viridans streptococci isolates from patients with endocarditis.

Effects of tigecycline, linezolid and vancomycin on biofilms of viridans streptococci isolates from patients with endocarditis.

Int J Artif Organs. 2007 Sep

Presterl E, Lassnigg A, Eder M, Reichmann S, Hirschl AM, Graninger W.
Department of Medicine I, Division of Infectious Diseases and Tropical Medicine, Medical University of Vienna, Vienna - Austria and Institute of Hygiene and Medical Microbiology, Division of Clinical Microbiology, Medical University of Vienna, Vienna - Austria.

Background: Endocarditis, and prosthetic valve endocarditis in particular, is a serious disease with high morbidity and mortality. We investigate the effects of tigecycline, linezolid and vancomycin on biofilms of viridans group streptococci (VGS) isolated from patients with definite native or prosthetic valve endocarditis.

Methods and Results: Ten of 20 VGS blood stream isolates from patients with endocarditis formed biofilms in the microtiter plate biofilm model. The minimal inhibitory concentrations (MIC) for tigecycline, linezolid and vancomycin were determined using the microdilution broth method. Biofilms were grown for 24 hours and were incubated with tigecycline, linezolid and vancomycin at increasing concentrations from 1-128x MIC of the isolate being tested. Biofilm thickness was quantified by measuring the optical density (OD) after dyeing it with crystal violet. The incubation of the biofilms with tigecycline, linezolid or vancomycin resulted in a significant reduction of OD compared to the control biofilm without antibiotic (p<0.05).>

Conclusions: In the present study on viridans streptococci isolated from patients with endocarditis, tigecycline and linezolid reduced the density of the biofilms as effectively as vancomycin. However, linezolid and vancomycin were bactericidal at higher concentrations. Linezolid and vancomycin at very high doses may be useful in the treatment of biofilm-associated diseases caused by VGS infections.

PMID: 17918125 [PubMed - as supplied by publisher]

Wednesday, September 26, 2007

Antibiotic prescription and prevalence rate in the outpatient paediatric population: analysis of surveys published during 2000-2005.

Antibiotic prescription and prevalence rate in the outpatient paediatric population: analysis of surveys published during 2000-2005.
Eur J Clin Pharmacol. 2007 Sep 21
Rossignoli A, Clavenna A, Bonati M.
Laboratory for Mother and Child Health, Mario Negri Institute for Pharmacological Research, via G. La Masa 19, 20156, Milan, Italy,

OBJECTIVE: To evaluate antibiotic paediatric consumption data in the community setting using data from studies published between 2000 and 2005 and to compare inter- and intra-country antibiotic prescribing patterns.

METHODS: A literature search was performed in EMBASE and MEDLINE to identify pharmacoepidemiological studies published between 2000 and 2005.

RESULTS: Large differences between studies were found, with significant heterogeneity in epidemiological indicators. Only 20 studies reporting comparable drug prescription data were considered in the analysis, all of which were from the USA, Canada, North-Central Europe and Italy. Pre-school children were reported as comprising the most exposed age group to antibiotic therapy (prevalence 72%; prescription rate 2.2 prescriptions/person per year). In the overall child and adolescent population (less or equal to 19 years), prevalence varied from 14 to 57% (mean 34%), and the prescription rate from 0.2 to 1.3 prescriptions/person per year. Relevant inter-country qualitative and quantitative differences in antibiotic prescribing were apparent, although these were observed in only a few countries: prevalence was higher in Italy and Canada (prevalence range 42-57%) and lower in the Netherlands and the United Kingdom (prevalence range 14-21%). Penicillins were the most prescribed antibiotics in all cases (40-70% of antibiotic prescriptions), followed by macrolides (16-45%), while cephalosporins accounted for a large proportion of the prescriptions in Italy (30-40%) and Canada, but were practically absent in North European prescriptions.

CONCLUSION: Comparative drug utilisation studies on antibiotic use in children are needed, as are improvements in regulatory and educational programmes aimed at limiting the number prescriptions given for antibiotics. Both approaches would address public health problems, such as bacterial resistance and safety and elevated costs, related to the use and misuse of these drugs.

PMID: 17891535 [PubMed - as supplied by publisher]

Wednesday, September 12, 2007

Evaluation of phenoxymethylpenicillin treatment of acute otitis media in children aged 2-16.

Evaluation of phenoxymethylpenicillin treatment of acute otitis media in children aged 2-16.

Scand J Prim Health Care. 2007 Sep

Neumark T, Mölstad S, Rosén C, Persson LG, Törngren A, Brudin L, Eliasson I.

Lindsdal Primary Health Centre, Kalmar, Sweden.

Keywords: Acute otitis media; antibiotics; AOM; children; family practice; general practice; PcV; phenoxymethylpenicillin; primary healthcare

Objective. To study the clinical recovery from acute otitis media (AOM) in children, 2-16 years of age, managed with or without treatment with phenoxymethylpenicillin (PcV). Design. An open, prospective randomized trial. Children aged between 2 and 16 years, presenting with one- or double-sided AOM (without perforation) with symptom duration of less than four days, were included. The children were randomized to PcV for five days or to no primary antibiotic treatment. A health score and compliance were registered on a daily basis for seven days.

Setting. A total of 32 health centres and 72 GPs in south-east Sweden. Subjects. Children aged 2-16 presenting with earache. Main outcome measures. Recovery time, symptom duration, frequency of complications (up to three months) and consumption of healthcare services independent of treatment with or without antibiotics.

Results. A total of 179 patients carried out the trial; 92 were randomized to PcV, 87 to no primary antibiotic treatment. The median recovery time was four days in both groups. Patients who received PcV had less pain (p <0.001)>

Conclusions. Our investigation supports that PcV treatment of AOM does not affect the recovery time or complication rates. PcV provided some symptomatic benefit in the treatment of AOM in otherwise healthy children, aged 2-16 years.


Monday, August 20, 2007

Efficacy of azithromycin in the treatment of childhood typhoid Fever.

Efficacy of azithromycin in the treatment of childhood typhoid Fever.
Mymensingh Med J. 2007 Jul
Islam MN, Rahman ME, Rouf MA, Islam MN, Khaleque MA, Siddika M, Hossain MA.
Dr Md Nazrul Islam, Assistant Registrar, Department of Paediatrics, Mymensingh Medical College Hospital, Mymensingh.

An intervention study was carried out in Paediatric wards for a period of one year from January 2003 to December 2003 to determine the efficacy and safety of azithromycin in the treatment of uncomplicated childhood typhoid fever.

A total of 50 cases were enrolled in the study. The inclusion criteria of the cases were: documented fever for more than 7 days plus two or more of the following clinical features: toxic appearance, abdominal tenderness, hepatomegaly, splenomegaly, diarrhoea, constipation and coated tongue plus positive Widal test and/or blood culture positivity.

Patients who had complication like gastrointestinal tract (GIT) haemorrhage; intestinal perforation and/or shock were excluded from the study. Data were collected in a structured questionnaire. Azithromycin was given at a dose of 10mg/kg /day for a period of 07 days. The time to defervescence was 3.82+/-1.49 days. The minimum defervescence time was 02 days and maximum was 07 days. Clinical cure rate was 94%. No serious adverse effect was noted related to azithromycin therapy except nausea, vomiting, and jaundice. Prior treatment with antibiotics did not affect defervescence time (P>0.05).

Pre-treatment febrile period has got positive and linear correlation with clinical response (r = +0.593). It was found that once daily administration of oral azithromycin for seven days in the treatment of uncomplicated typhoid fever was effective and reasonably safe.


Friday, August 03, 2007

The future of natural products as a source of new antibiotics

The future of natural products as a source of new antibiotics
Curr Opin Investig Drugs. 2007 Aug

Luzhetskyy A, Pelzer S, Bechthold A.
Albert-Ludwigs-Universität Freiburg, Institut für Pharmazeutische Wissenschaften, Pharmazeutische Biologie und Biotechnologie, Stefan-Meier-Straße 19, D-79194 Freiburg, Germany.

One reason for the current crisis in antibiotic development is the low return on investment, which is intrinsic to anti-infective drug development. Despite this, smaller pharmaceutical companies are attempting to address the medical need for new antibiotics. Natural products have played a major role in antibiotic drug discovery since 1941 when penicillin was introduced to the market, and currently natural products are again the most important source for promising drug candidates. This review discusses novel methods and technologies that will increase the success rate for identifying novel antibiotics from natural sources.

PMID: 17668363 [PubMed - as supplied by publisher]

New aspects of natural products in drug discovery
Trends Microbiol. 2007 Jun

Lam KS.
Nereus Pharmaceuticals Inc., 10480 Wateridge Circle, San Diego, CA 92121, USA.

During the past 15 years, most large pharmaceutical companies have decreased the screening of natural products for drug discovery in favor of synthetic compound libraries. Main reasons for this include the incompatibility of natural product libraries with high-throughput screening and the marginal improvement in core technologies for natural product screening in the late 1980s and early 1990 s. Recently, the development of new technologies has revolutionized the screening of natural products. Applying these technologies compensates for the inherent limitations of natural products and offers a unique opportunity to re-establish natural products as a major source for drug discovery. Examples of these new advances and technologies are described in this review.

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