Selection and use of anti-infective agents for intra-abdominal infections

Selection and use of anti-infective agents for intra-abdominal infections

Arq Gastroenterol. 2007

Coelho JC, Baretta GA, Okawa L.
Serviço de Cirurgia do Aparelho Digestivo, Hospital de Clínicas, Universidade Federal do Paraná, Curitiba, PR.

Correspondence:

Dr. Júlio C. U. Coelho Rua Bento Viana, 1140 – apt.2202 80240-110 – Curitiba, PR E-mail: juliocoelho@bbs2.sul.com.br

Headings: Abdomen. Infection. Cross infection. Anti-bacterial agents.

BACKGROUND: Intra-abdominal infections are common and are associated with elevated morbidity and mortality. The microorganisms that cause intra-abdominal infections are usually from the gastrointestinal flora, mainly E. coli and Bacteroides fragilis.

AIM: To present a review of the selection and use of antibiotics in intra-abdominal infections.

CONCLUSIONS: Appropriate use of antibiotics is essential to control infection and to reduce treatment failure. Antibiotics are initiated whenever intra-abdominal infection is suspected and the antimicrobial agents are selected based on the most common microorganisms involved. In addition, efficacy, cost, safety, and posologic regimen are considered for an appropriated selection. Antibiotic regimen is different whether the infection is acquired in the community or at hospital due to the more resistant flora in the latter.

SciFlo Brazil

Successful treatment of vancomycin-resistant enterococcus ventriculitis in a child.

Successful treatment of vancomycin-resistant enterococcus ventriculitis in a child.

Braz J Infect Dis. 2007 Apr

Silva PS, Monteiro Neto H, Sejas LM.
Pediatric Intensive Care Unit, Department of Pediatrics, State Hospital of Diadema, Federal University of São Paulo, São Paulo, SP, Brazil.

Key-Words: Vancomycin, resistance, treatment

Abstract

Enterococci are an uncommon cause of CNS infection. A 20 month-old boy, diagnosed with hydrocephalus with ventriculoperitoneal shunt and history of lengthy hospitalization and use of wide spectrum antibiotics, was admitted to the pediatric intensive care unit diagnosed with ventriculitis. On the 14th day of empirical antibiotic therapy (vancomycin and meropenem) the child presented fever while the CSF sample culture evidenced vancomycin-resistant Enterococcus faecium.

The patient received intravenous linezolid achieving cerebrospinal fluid sterilization.

Conclusion: Intravenous linezolid appears to be a safe and effective therapy for vancomycin-resistant enterococcus ventriculoperitoneal shunt infection.

Case Report
A 20 month-old boy, with underlying diagnosis of neurodevelopmental delay and hydrocephalus with ventriculoperitoneal shunt (VPS) secondary to Pneumococcus meningitis at 6 months of life, presented a cardiorespiratory arrest on his arrival in hospital, and was then resuscitated over 23 minutes. The infant remained hospitalized for 10 days within the pediatric intensive care unit (PICU), diagnosed with aspirative pneumonia and cardiogenic shock, receiving oxacillin and ceftriaxone.
On the 18th day, the patient was readmitted to the PICU with a diagnosis of septic shock due to central venous catheter-related infection, being discharged from the PICU on the 7th day, having received vancomycin and cefepime for a total of 3 weeks. On the 39th day he was readmitted to the PICU diagnosed with ventriculitis. The cerebrospinal fluid (CSF) sample obtained by reservoir puncture revealed 71 cells/mm3 (72% neutrophils; glucose 13 mg/dL and protein 69 mg/dL). Cultures were negative. The patient received external ventricular drain associated with vancomycin and meropenem empirically for 4 weeks, undergoing a VPS on the 30th PICU day. On the 14th postoperative (PO) day, the patient developed perivalvular abscess, the CSF obtained from the shunt reservoir presented 74 cells/mm3 (79% neutrophils), upon which the patient was submitted to external ventricular shunt (EVS) whilst vancomycin and meropenem were resumed. On the 6th PO day after EVS, fluconazole was associated due to the presence of yeast in a routine CSF sample. Cultures for fungus were negative. On the 14th day of antibiotic therapy, the patient evolved with fever (39ºC), presenting the following laboratorial exams: white blood cells (WBC) 23,000/mm3, platelets 156,000/mm3, C-reactive protein 20 mg/dL, CSF with 15 cells (90% neutrophils), glucose 45 g/dL, protein 910 g/dL, Gram stain showed Gram-positive cocci in chains, and 2 serial CSF cultures yielded Enterococcus faecium resistant to vancomycin, ampicillin, streptomycin, ciprofloxacin, chloramphenicol and susceptible to gentamicin. The vancomycin minimum inhibitory concentration (MIC) of this isolate was > 32 µg/mL (using an E-test method with an inoculum density of 0.5 McFarland standard). Based on this information, he was switched to linezolid monotherapy, dosed at 10 mg/kg intravenously every 8 hours.
Following the 2nd day of linezolid, the patient became afebrile, and after the 3rd day had sterile CSF. Following 4-week treatment with linezolid, the patient had a new VPS in place (CSF: 1 cell/mm3, glucose 54 g/dL and protein 90 g/dL) and C-reactive protein of 1.78 mg/dL. Treatment continued for a further 2 weeks, during which time CSF samples remained sterile. Concentrations of linezolid in CSF were not recorded. The patient tolerated the 6-week treatment without showing evidence of bone marrow suppression. Fecal cultures obtained during treatment with linezolid were negative. The patient evolved requiring ventilation assistance due to neurologic compromise, and was cared for in an intermediate care unit.

Discussion
The emergence of nosocomially acquired vancomycin-resistant enterococci has become a significant concern and a treatment challenge to physicians [3]. Approximately 12% to 18% of enterococci in the United States exhibit vancomycin resistance [3].

Risk factors for vancomycin-resistant enterococcus (VRE) colonization in children include young age, use of invasive devices, antimicrobial drug administration, immunosuppression, low birth weight, and underlying malignancy [10]. Such patients have commonly been treated with vancomycin or broad-spectrum antibiotics before VRE isolation [11]. Two important factors predisposing patients to VRE infection are the percentage of hospital days receiving antimicrobial therapy of any type and the number of days receiving intravenous vancomycin [7]. Our patient had received several weeks of broad-spectrum antibiotics before developing VRE meningitis; this prolonged use of antibiotics, associated with the long stay in hospital were likely contributory factors in both colonization and subsequent infection with VRE. However, treatment with lengthy courses of broad-spectrum antibiotics is often unavoidable in critically ill patients.

The National Nosocomial Infections Surveillance system of the Centers for Disease Control and Prevention reported vancomycin resistance in 28.5% of nosocomial enterococcal intensive care unit infections in 2003 [12]. In a recent study, 14% of VRE-colonized patients progressed to infection within 15 days of a positive surveillance culture [13]. A recent review noted that, although Enterococcus faecalis is responsible for 80% of enterococcal infections, E. faecium strains account for 98% of vancomycin-resistant cases [14].

There are no established guidelines for the treatment of central nervous system infection caused by VRE. Therapeutic options for vancomycin-resistant enterococci are limited because these organisms are usually resistant to multiple antimicrobial agents. Treatment often has to include investigational drugs or less tested new drugs. In our patient the therapy included intravenous linezolid. To the best of our knowledge, there has only been 1 previous case report of ventriculitis due to enterococcus in a child treated successfully with linezolid [4].

Linezolid, the first member of the oxazolidinones class of antibiotics licensed by the U.S. Food and Drug Administration (FDA), inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit. It is approved for use in adults and children for serious infections caused by Enterococcus faecium or Enterococcus faecalis including vancomycin-resistant strains (VRE), Staphylococcus aureus including methicilllin-resistant strains (MRSA), coagulate-negative staphylococci and streptococci including penicillin-resistant Streptococcus pneumoniae [15]. Linezolid is essentially bacteriostatic. In vitro time-kill experiments against multidrug-resistant (including vancomycin-resistant) enterococci, linezolid was not bactericidal but had greater bacteriostatic activity against these organisms [16].

CSF penetration of linezolid suggests utility in treatment of meningitis and intracranial prosthetic device infections. In individuals with noninflamed meninges, linezolid concentrations in CSF were 70% of plasma concentrations [17]. In adults, reversible thrombocytopenia is the major hematologic consequence of linezolid use, generally occurring after > 2 weeks of treatment and thought to be due to transient bone marrow suppression. In children, thrombocytopenia is less common; however, a complete blood count should be monitored weekly while children are receiving linezolid [17]. In adults, linezolid-induced neuropathy has been reported among patients receiving the drug for > 6 months.

Vancomycin and aminoglycosides with variable penetration of the blood-brain barrier and monitoring CSF levels is recommended. Intraventricular administration of antimicrobials with irregular penetration of blood-brain barrier makes theoretical sense but is controversial [18]. Problems with intraventricular antibiotics include allergic reactions, drug-induced inflammation and toxic or inadequate concentrations [18]. Even though our case presented gentamycin-susceptible enterococcus, the patient was successfully treated without needing intraventricular administration of drugs.

Optimal management of ventricular shunt infection requires removal of the shunt, placement of a temporary external ventricular drain (EVD), followed by reinternalization after CSF sterilization. A recent analysis strongly confirmed this as the most effective treatment method [19].

Length of time on antibiotic therapy in patients with ventriculoperitoneal shunt infection remains controversial. Studies employing linezolid for the treatment of VPS infections range from 3 to 12 weeks in length [4,8,20,21]. Despite receiving prolonged treatment, our patient presented no bone marrow compromise according to serial hemograms. However, peripheral neuropathic signs could not be assessed in this case because the patient presented severe neurologic compromise due to the underlying disease and comorbidity.

In conclusion, intravenous linezolid appears to be a safe and effective therapy for vancomycin-resistant enterococcus ventriculitis. Our success with linezolid in this instance is encouraging for the future role of this class of drugs for the treatment of shunt infections.

ScieFLO Brazil

Pharmacokinetics and pharmacodynamics of antimicrobials

Pharmacokinetics and pharmacodynamics of antimicrobials

Clin Infect Dis. 2007 Jul

Drusano GL.
Ordway Research Institute, Albany, NY 12208, USA. gdrusano@ordwayresearch.org

Antibiotics are some of our most commonly used drugs. Until recently, little has been known about how to optimize administration of these agents. Unfortunately, the rate of discovery of new antibiotics has been declining, coincident with the explosion in the number of multidrug-resistant organisms in both the community and hospital environments. This development makes the identification of optimal regimens that will result in good clinical and microbiological outcomes important, but it also makes clear the necessity of identifying regimens that will suppress the emergence of resistant organisms. Given that new agents for multidrug-resistant pathogens will take nearly a decade to become available to physicians, keeping organisms susceptible to drugs that are already available is even more critical. Pharmacodynamics allows identification of the drug exposure measure that is closely associated with the ability to kill organisms and, also, to suppress the emergence of resistant subpopulations of organisms. Use of Monte Carlo simulation allows identification of drug doses in the clinical arena to accomplish these ends. Such approaches should be applied to all old and new antibacterial agents.

Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial.

Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial.
BMJ. 2007 Jun 29

Hickson M, D'Souza AL, Muthu N, Rogers TR, Want S, Rajkumar C, Bulpitt CJ.
Nutrition and Dietetic Research Group, Faculty of Medicine, Imperial College, London W12 0HS.

OBJECTIVE: To determine the efficacy of a probiotic drink containing Lactobacillus for the prevention of any diarrhoea associated with antibiotic use and that caused by Clostridium difficile. DESIGN: Randomised double blind placebo controlled study.

PARTICIPANTS: 135 hospital patients (mean age 74) taking antibiotics. Exclusions included diarrhoea on admission, bowel pathology that could result in diarrhoea, antibiotic use in the previous four weeks, severe illness, immunosuppression, bowel surgery, artificial heart valves, and history of rheumatic heart disease or infective endocarditis.

INTERVENTION: Consumption of a 100 g (97 ml) drink containing Lactobacillus casei, L bulgaricus, and Streptococcus thermophilus twice a day during a course of antibiotics and for one week after the course finished. The placebo group received a longlife sterile milkshake.

MAIN OUTCOME MEASURES: Primary outcome: occurrence of antibiotic associated diarrhoea. Secondary outcome: presence of C difficile toxin and diarrhoea.

RESULTS: 7/57 (12%) of the probiotic group developed diarrhoea associated with antibiotic use compared with 19/56 (34%) in the placebo group (P=0.007). Logistic regression to control for other factors gave an odds ratio 0.25 (95% confidence interval 0.07 to 0.85) for use of the probiotic, with low albumin and sodium also increasing the risk of diarrhoea. The absolute risk reduction was 21.6% (6.6% to 36.6%), and the number needed to treat was 5 (3 to 15). No one in the probiotic group and 9/53 (17%) in the placebo group had diarrhoea caused by C difficile (P=0.001). The absolute risk reduction was 17% (7% to 27%), and the number needed to treat was 6 (4 to 14).

CONCLUSION: Consumption of a probiotic drink containing L casei, L bulgaricus, and S thermophilus can reduce the incidence of antibiotic associated diarrhoea and C difficile associated diarrhoea. This has the potential to decrease morbidity, healthcare costs, and mortality if used routinely in patients aged over 50. Trial registration National Research Register N0016106821.

PMID: 17604300 [PubMed - as supplied by publisher]

Tetracyclines and Methicillin-Resistant Staphylococcus Aureus MRSA

Tetracyclines as an Oral Treatment Option for Patients with Community-Onset Methicillin-Resistant Staphylococcus aureus Skin and Soft-Tissue Infections.

Antimicrob Agents Chemother. 2007 Jun 18

Ruhe JJ, Menon A.

Division of Infectious Diseases, Department of Medicine, University of Arkansas for Medical Sciences; and Central Arkansas Veterans Healthcare System, Little Rock, Arkansas, U.S.A.

Few data exist on the clinical utility of the second-generation tetracyclines doxycycline and minocycline for the treatment of community-associated methicillin-resistant Staphylococcus aureus (MRSA) skin and soft-tissue infections (SSTI). We performed a retrospective cohort study on 282 patients who presented with MRSA SSTI to the emergency room or outpatient clinic at two tertiary medical centers between October 2002 and February 2007. Median MRSA susceptibility to tetracycline was 95%. Time zero was defined as the time of the first incision and drainage procedure or, if none was performed, the time of the first positive wound culture. The median patient age was 48 years.

Abscesses constituted the majority of clinical presentations (75%), followed by furuncles or carbuncles (13%), and cellulitis originating from a purulent focus of infection (12%). 225 (80%) patients underwent incision and drainage. Doxycycline or minocycline was administered in 90 (32%) episodes; the other 192 SSTI were treated with beta-lactams. Treatment failure, defined as the need for a second incision and drainage procedure and/or admission to the hospital by at least two days after time zero, was diagnosed in 28 (10%) episodes at a median of three days after time zero. On logistic regression analysis, receipt of a beta-lactam agent was the only clinical characteristic associated with treatment failure (adjusted OR 3.94; 95% CI, 1.28-12.15; P=0.02).

The second-generation tetracyclines appear to be a reasonable oral treatment option for patients with community-onset MRSA SSTI in areas where MRSA are susceptible to the tetracyclines.

Antimicrobial Agents and Chemotherapy

The effect of the timing of antibiotics and surgical treatment on infection rates in open long-bone fractures: A 9-year prospective study from a distr

The effect of the timing of antibiotics and surgical treatment on infection rates in open long-bone fractures: A 9-year prospective study from a district general hospital.

Injury. 2007 Jun 19
Al-Arabi YB, Nader M, Hamidian-Jahromi AR, Woods DA.
The Great Western Hospital, Marlborough Road, Swindon SN3 6BB, United Kingdom.

AIMS: To determine whether a delay of greater than 6h from injury to initial surgical debridement and the timing of antibiotic administration affect infection rates in open long-bone fractures.

METHODS: We studied 248 consecutive open long-bone fractures in 237 patients over a 9-year period. The patients were followed until clinical or radiological union occurred or until a secondary procedure for non-union or infection was performed.

RESULTS: Surgical debridement was performed within 6h of injury in 62% of cases and after 6h in 38% of cases. Infection rates were 7.8% and 9.6%, respectively, and the difference was not statistically significant (p=0.6438). The timing of antibiotic administration was not significantly related to the infection rate.

CONCLUSION: Whilst open long-bone fractures should be treated expeditiously, we suggest that adherence to a 6h window has not been shown to affect infection rates nor has the timing of antibiotic administration during the acute phase.

Elsevier

Comparative activities of antibiotics against intracellular non-typeable Haemophilus influenzae.

Comparative activities of antibiotics against intracellular non-typeable Haemophilus influenzae.
Wien Klin Wochenschr. 2007 Jun

Kratzer C, Graninger W, Macfelda K, Buxbaum A, Georgopoulos A.
Department of Internal Medicine I, Division of Infectious Diseases and Tropical Diseases, Medical University of Vienna, Vienna, Austria, apostolos.georgopoulos@meduniwien.ac.at.

INTRODUCTION: Non-typeable Haemophilus influenzae (NTHi) is a major bacterial pathogen of community-acquired respiratory tract infection and is usually found extracellularly, although studies have revealed that NTHi may possess the ability to invade human epithelial cells where it is then protected against attack by the local immune system and partly against the effect of antibiotics. The aim of the present study was to assess the ability of ampicillin, azithromycin, telithromycin, ciprofloxacin and moxifloxacin, five antibiotics in common clinical use, to kill NTHi within bronchial epithelial cells.

METHODS: Confluent human bronchial epithelial cells were infected with NTHi 77, a particularly invasive clinical strain. Extracellular bacterial cells were killed with gentamicin and the intracellular bacteria were incubated with antibiotics at concentrations of 1 mg/l or 10 mg/l for 4 h or 8 h. Viable intracellular bacteria were counted after lysis of the epithelial cells.

RESULTS: With the exception of ampicillin, all the antibiotics caused significant reduction of intracellular bacteria at concentrations of 10 mg/l and exposure for 4 h or at 1 mg/l for 8 h. At 1 mg/l, moxifloxacin eliminated 94% of intracellular NTHi after 4 h and 98% after 8 h; ciprofloxacin, azithromycin and telithromycin only achieved killing indices below 75 after 4 h but 86-90% killing after 8 h. At 10 mg/l, moxifloxacin, ciprofloxacin, telithromycin and azithromycin were able to achieve 99.7%, 96.3%, 86.7% and 74.7% eradication of intracellular bacteria, respectively, after exposure for 4 h.

CONCLUSION: These results demonstrate the rapid antibacterial efficacy of moxifloxacin against intracellular NTHi in vitro. Moxifloxacin, which combines high extracellular and intracellular activities, could be an important tool in the treatment of recurrent respiratory tract infections.

PMID: 17571234 [PubMed - as supplied by publisher]

Emergence and maintenance of resistance to fluoroquinolones and coumarins in Staphylococcus aureus: predictions from in vitro studies.

Emergence and maintenance of resistance to fluoroquinolones and coumarins in Staphylococcus aureus: predictions from in vitro studies.

J Antimicrob Chemother. 2007 Jun 7

Vickers AA, O'neill AJ, Chopra I.
Antimicrobial Research Centre and Research Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, UK.

Objectives: Fluoroquinolones and coumarins interfere with the activity of bacterial type II topoisomerase enzymes. We examined the development of resistance to these agents in Staphylococcus aureus and determined the effect of simultaneous topoisomerase IV and DNA gyrase mutations on the biological fitness of the organism.

This work aimed to gain insight into how such mutants might arise and survive in the clinical environment. Methods Spontaneous mutants resistant to fluoroquinolones and coumarins were selected in S. aureus. Resistance mutations were identified by DNA sequencing of PCR amplicons corresponding to the genes encoding topoisomerase IV and DNA gyrase. In vitro fitness of resistant mutants was compared with the antibiotic-susceptible progenitor strain using pair-wise competition assays.

Results: Mutants simultaneously resistant to both a fluoroquinolone and either of the coumarins, novobiocin or coumermycin A1, could not be recovered following a single-step selection. However, mutants concurrently resistant to both classes of antimicrobial could be generated by step-wise selections. These mutants demonstrated reductions in competitive fitness of up to 36%.

Conclusions: Dual-targeting of topoisomerase IV and DNA gyrase enzymes, for example with the combination of a fluoroquinolone and a coumarin agent, could minimize the emergence of resistance to these drugs in S. aureus. However, resistance-associated fitness costs may not be sufficient to limit the survival of mutants with dual resistance, if they arose in the clinical setting.

Antimicrobial Chemotherapy

Antibiotics, Physician outcome judgements, inappropriate treatment

Do physician outcome judgments and judgment biases contribute to inappropriate use of treatments? Study Protocol.

Implement Sci. 2007 Jun 7

Brehaut JC, Poses R, Shojania KG, Lott A, Man-Son-Hing M, Bassin E, Grimshaw J.

ABSTRACT: BACKGROUND: There are many examples of physicians using treatments inappropriately, despite clear evidence about the circumstances under which the benefits of such treatments outweigh their harms. When such over- or under- use of treatments occurs for common diseases, the burden to the healthcare system and risks to patients can be substantial. We propose that a major contributor to inappropriate treatment may be how clinicians judge the likelihood of important treatment outcomes, and how these judgments influence their treatment decisions. The current study will examine the role of judged outcome probabilities and other cognitive factors in the context of two clinical treatment decisions: 1) prescription of antibiotics for sore throat, where we hypothesize overestimation of benefit and underestimation of harm leads to over-prescription of antibiotics; and 2) initiation of anticoagulation for patients with atrial fibrillation (AF), where we hypothesize that underestimation of benefit and overestimation of harm leads to under-prescription of warfarin.

METHODS: For each of the two conditions, we will administer surveys of two types (Type 1 and Type 2) to different samples of Canadian physicians. The primary goal of the Type 1 survey is to assess physicians' perceived outcome probabilities (both good and bad outcomes) for the target treatment. Type 1 surveys will assess judged outcome probabilities in the context of a representative patient, and include questions about how physicians currently treat such cases, the recollection of rare or vivid outcomes, as well as practice and demographic details. The primary goal of the Type 2 surveys is to measure the specific factors that drive individual clinical judgments and treatment decisions, using a 'clinical judgment analysis' or 'lens modeling' approach. This survey will manipulate eight clinical variables across a series of sixteen realistic case vignettes. Based on the survey responses, we will be able to identify which variables have the greatest effect on physician judgments, and whether judgments are affected by inappropriate cues or incorrect weighting of appropriate cues. We will send antibiotics surveys to family physicians (300 per survey), and warfarin surveys to both family physicians and internal medicine specialists (300 per group per survey), for a total of 1,800 physicians. Each Type 1 survey will be two to four pages in length and take about fifteen minutes to complete, while each Type 2 survey will be eight to ten pages in length and take about thirty minutes to complete.

DISCUSSION: This work will provide insight into the extent to which clinicians' judgments about the likelihood of important treatment outcomes explain inappropriate treatment decisions. This work will also provide information necessary for the development of an individualized feedback tool designed to improve treatment decisions. The techniques developed here have the potential to be applicable to a wide range of clinical areas where inappropriate utilization stems from biased judgments.

PMID: 17555586 [PubMed - as supplied by publisher]

Appropriate usage of antibiotics by therapeutic drug monitoring

Appropriate usage of antibiotics by therapeutic drug monitoring

Yakugaku Zasshi. 2007 Jun

Kokubun H, Kimura T, Yago K.
Department of Pharmacy, Kitasato University Hospital.

Aminoglycosides are mainly distributed in the extracellular fluid, so when they are given to neonates who have a large amount of extracellular fluid, their distribution is increased. In our data, the volume of distribution (Vd) of Arbekacin in the neonates was twice that of the adults, 0.54 l/kg. Therefore, the dose per weight of aminoglycosides to the neonates should be increased more than to the adults. In the renal function of the neonates, differentiation of the nephron is completed within 36 weeks after conception, but it is functionally immature. In our data, renal drug excretion increased rapidly in the post-conceptional ages (PCAs) of 34-35 weeks. Consequently, we based the Arbekacin administration schedule for the neonates on the PCAs. There is excellent correlation between serum level of vancomicin (VCM) and dosexserum creatinine (Scr)/weight in the haemodialysis patients, suggesting that we can use weight and Scr to set the VCM administration schedule for these patients. We also established on administration schedule of Teicoplanin for the haemodialysis patients. In this article, we present the TDM analysis result of the antibiotics in our hospital.

PMID: 17541241

[PubMed - in process]

Zymar (Gatifloxacin 0.3%) Shows Excellent Gram-Negative Activity Against Serratia marcescens and Pseudomonas aeruginosa

Zymar (Gatifloxacin 0.3%) Shows Excellent Gram-Negative Activity Against Serratia marcescens and Pseudomonas aeruginosa in a New Zealand White Rabbit Keratitis Model.

Cornea. 2007 Jun

Mah FS,
Romanowski EG,
Kowalski RP,
Yates KA,
Gordon YJ.

From the Charles T. Campbell Ophthalmic Microbiology Laboratory, UPMC Eye Center, Ophthalmology and Visual Sciences Research Center, Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA.

PURPOSE: Whereas gatifloxacin, a newer fluoroquinolone, was engineered to increase its Gram-positive potency, we assessed whether it still retained significant Gram-negative activity in vivo. Specifically, we compared the efficacy of Zymar (gatifloxacin 0.3%), Ciloxan (ciprofloxacin 0.3%), and fortified tobramycin (14 mg/mL) in the treatment of experimental Gram-negative bacterial infections of Serratia marcescens (SM) and Pseudomonas aeruginosa (PA) in the New Zealand White (NZW) rabbit keratitis model.

METHODS: A total of 30 NZW rabbits each were intrastromally inoculated in both eyes with approximately 1000 CFU of SM and PA. By E-test, the minimum inhibitory concentrations (MICs; mug/mL) for SM were gatifloxacin (0.125), ciprofloxacin (0.047), and tobramycin (1.5), and for PA were gatifloxacin (0.125), ciprofloxacin (0.19), and tobramycin (0.5). After 16 hours, the rabbits were divided into 4 treatment groups: (1) Zymar, (2) Ciloxan, (3) fortified tobramycin, and (4) saline control. One drop was instilled in both eyes every 15 minutes for 5 doses and then every 30 minutes for 14 doses. One hour after the final treatment, the animals were euthanized, and bacterial colony counts from the corneas were determined.

RESULTS: For SM, Zymar and Ciloxan significantly reduced the colony counts compared with tobramycin and saline control. Zymar was more effective than Ciloxan.For PA, all antibiotics reduced equivalently the colony counts compared with the saline control

CONCLUSIONS: The enhanced Gram-positive activity of gatifloxacin is not associated with any decreased Gram-negative activity in vivo. Zymar may prove useful for SM and PA keratitis.

PMID: 17525656 [PubMed - in process]

Review article: the role of antibiotics vs. conventional pharmacotherapy in treating symptoms of irritable bowel syndrome.

Review article: the role of antibiotics vs. conventional pharmacotherapy in treating symptoms of irritable bowel syndrome.

Aliment Pharmacol Ther. 2007 Jun

Frissora CL,
Cash BD.
Division of Gastroenterology and Hepatology, Weill Cornell Medical College of Cornell University, New York, NY, USA.

Background

The concept of augmenting the management of irritable bowel syndrome with antibiotics is evolving, and many questions remain regarding this therapy relative to known and hypothesized irritable bowel syndrome pathophysiology. The clinical evidence of small intestinal bacterial overgrowth as an important aetiology of irritable bowel syndrome continues to accumulate. Clinical symptoms of bacterial overgrowth and irritable bowel syndrome are similar; however, a definitive cause-and-effect relationship remains unproven. It is unclear whether motility dysfunction causes bacterial overgrowth or gas products of enteric bacteria affect intestinal motility in irritable bowel syndrome.

Aim

To discusses the efficacy and tolerability of current symptom-directed pharmacotherapies and of antibiotics in the treatment of irritable bowel syndrome. Methods A computerized search of PubMed was performed with search terms 'IBS', 'pharmacotherapy' and 'antibiotics'. Relevant articles were selected, and the reference list of selected articles was reviewed to identify additional references.

Results

Antibiotic treatment benefits a subset of irritable bowel syndrome patients. The non-absorbed antibiotic rifaximin has a favourable safety and tolerability profile compared with systemic antibiotics and demonstrates a therapeutic efficacy comparable with symptom-based irritable bowel syndrome pharmacotherapies.

Conclusion

Rifaximin is the only antibiotic with demonstrated sustained benefit beyond therapy cessation in irritable bowel syndrome patients in a placebo-controlled trial. Whether antibiotics can improve quality of life in patients with irritable bowel syndrome warrants further research.

PMID: 17509095 [PubMed - in process]

Fengycin antibiotics isolated from B-FS01 culture inhibit the growth of Fusarium moniliforme Sheldon ATCC 38932.

Fengycin antibiotics isolated from B-FS01 culture inhibit the growth of Fusarium moniliforme Sheldon ATCC 38932.
FEMS Microbiol Lett. 2007 May 8

Hu LB,
Shi ZQ,
Zhang T,
Yang ZM.
College of Life Sciences, Nanjing Agricultural University, Nanjing, China.

Strain B-FS01, isolated from rape (Brassica napus) stem infected by Slerotinia sclerotiorum and identified as Bacillus subtilis, exhibited predominantly antagonistic activities against Fusarium moniliforme Sheldon ATCC 38932. Antifungal active compounds (AAC) were isolated and purified from the cultures of strain B-FS01 against ATCC 38932. The HPLC/electron spray ionization/collision-induced dissociation mass spectrum of AAC revealed a cluster of fengycin homologues containing fengycins A, fengycins B and a new type of fengycin. Further toxic assay of AAC in vitro against F. moniliforme indicated that AAC could strongly inhibit the growth of both mycelia and spores. In addition, treatment with AAC significantly modified the maize seed infection by ATCC 38932.

PMID: 17490402 [PubMed - as supplied by publisher]

Antibiotic Treatment of the Tick Vector Amblyomma americanum Reduced Reproductive Fitness.

Antibiotic Treatment of the Tick Vector Amblyomma americanum Reduced Reproductive Fitness.

PLoS ONE. 2007 May

Zhong J,
Jasinskas A,
Barbour AG.
Department of Microbiology and Molecular Genetics, Department of Medicine and Pacific-Southwest Center for Biodefense and Emerging Infections, University of California Irvine, Irvine, California, United States of America.

BACKGROUND: The lone star tick Amblyomma americanum is a common pest and vector of infectious diseases for humans and other mammals in the southern and eastern United States. A Coxiella sp. bacterial endosymbiont was highly prevalent in both laboratory-reared and field-collected A. americanum. The Coxiella sp. was demonstrated in all stages of tick and in greatest densities in nymphs and adult females, while a Rickettsia sp. was less prevalent and in lower densities when present.

METHODOLOGY/PRINCIPAL FINDINGS: We manipulated the numbers of both bacterial species in laboratory-reared A. americanum by injecting engorged nymphs or engorged, mated females with single doses of an antibiotic (rifampin or tetracycline) or buffer alone. Burdens of the bacteria after molting or after oviposition were estimated by quantitative polymerase chain reaction with primers and probes specific for each bacterial species or, as an internal standard, the host tick. Post-molt adult ticks that had been treated with rifampin or tetracycline had lower numbers of the Coxiella sp. and Rickettsia sp. and generally weighed less than ticks that received buffer alone. Similarly, after oviposition, females treated previously with either antibiotic had lower burdens of both bacterial species in comparison to controls. Treatment of engorged females with either antibiotic was associated with prolonged time to oviposition, lower proportions of ticks that hatched, lower proportions of viable larvae among total larvae, and lower numbers of viable larvae per tick. These fitness estimators were associated with reduced numbers of the Coxiella sp. but not the Rickettsia sp.

CONCLUSION/SIGNIFICANCE: The findings indicate that the Coxiella sp. is a primary endosymbiont, perhaps provisioning the obligately hematophagous parasites with essential nutrients. The results also suggest that antibiotics could be incorporated into an integrated pest management plan for control of these and other tick vectors of disease.

PMID: 17476327 [PubMed - in process]

Locally Administered Antibiotics for Prophylaxis Against Surgical Wound Infection

Locally Administered Antibiotics for Prophylaxis Against Surgical Wound Infection
The Journal of Bone and Joint Surgery (American). 2007;89:929-933.doi:10.2106/JBJS.F.00919

An in Vivo Study Seth R. Yarboro, BS1, Elyse J. Baum, BS1 and Laurence E. Dahners, MD1
1 Department of Orthopaedics, University of North Carolina at Chapel Hill, CB 7055, Chapel Hill, NC 27599-7055. E-mail address for L.E. Dahners: led@med.unc.edu

Investigation performed at the University of North Carolina at Chapel Hill, Chapel Hill, North Carolina

Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants of less than $10,000 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

A commentary is available with the electronic versions of this article, on our web site and on our quarterly CD-ROM (call our subscription department, at 781-449-9780, to order the CD-ROM).

Background: Currently, the standard for prophylaxis against surgical infection consists of perioperative systemic antibiotics. In this study, we investigated the relative efficacy of various methods of antibiotic delivery for the prevention of surgical wound infections. We hypothesized that sustained release of local antibiotics inside the wound cavity by a drug delivery system would be more effective than systemically administered antibiotics.

Methods: Using a rat model, we inoculated a surgical wound in the quadriceps muscle with 8.0 x 105 colony-forming units of Staphylococcus aureus and then administered one of seven types of treatment: no treatment (control), bacitracin irrigation, calcium sulfate flakes, systemic gentamicin, local aqueous gentamicin, local gentamicin-loaded calcium sulfate flakes, and a combination of local gentamicin-loaded calcium sulfate and systemic gentamicin. The seven treatment groups consisted of ten rats each. To further evaluate a trend, the group treated with systemic gentamicin and the one treated with local gentamicin solution were extended to include twenty-five and twenty-seven rats, respectively. At forty-eight hours postoperatively, specimens from the wounds were obtained for quantitative culture.

Results: The control group, the group treated with bacitracin irrigation, and the one treated with plain calcium sulfate had very high bacterial counts and high mortality rates while the groups treated with gentamicin had low bacterial counts and a 100% survival rate. Local gentamicin was significantly more effective than systemic gentamicin in reducing bacterial counts.

Conclusions: The gentamicin-loaded calcium sulfate flakes did not result in bacterial counts that were significantly lower than those following systemic administration of gentamicin, which refuted our hypothesis. However, gentamicin solution injected directly into the closed wound did result in levels of bacteria that were significantly lower than those following treatment with the systemic gentamicin.

Clinical Relevance: We believe that a high initial concentration of locally applied antibiotic inside the wound effectively kills bacteria present in the wound cavity, where systemic antibiotics have poor penetration, suggesting that this method of antibiotic administration may be a desirable adjunct for prophylaxis against infection in surgical wounds.

The Journal of Bone and Joint Surgery (American)

Antibiotics for Superbacteria

New antibiotics discovered that could beat back superbacteria

Researchers hope to stop virulent form of staph

By LEE BOWMANSCRIPPS HOWARD NEWS SERVICE

Researchers reported Friday they have found four promising antibiotics in chemical families never used before against germs through a novel testing tool that can screen dozens of compounds at once.

The four compounds appear to kill bacteria, at least in a lab dish. Because they probably attack bacteria in different ways, germs should take some time to develop resistant strains.
"These represent whole new classes of antibiotic agents," said Helen Blackwell, lead author of a University of Wisconsin-Madison report on the discoveries published in the journal Chemistry and Biology.

Also, while the most potent compounds were able to kill several dangerous strains of bacteria, the strongest activity was against a highly drug-resistant strain of staph infection (Staphylococcus aureus) that has been plaguing hospitals for years and has recently become common in community settings.

"Strains are emerging that are drug-resistant to all known antibiotics," Blackwell said. "This is not a problem that is going to go away, and actually it's going to get worse. There's a sense of urgency."

The best approach is to be able to hit bacteria with drugs they have not seen before. But finding a potentially useful drug against a broad spectrum of germs is not much different from finding a needle in a haystack.

Blackwell's team designed a way to sift through a lot of hay at once with a device it calls a small-molecule macroarray. The scientists synthesize molecules on a flexible, paperlike sheet, building a compound from the bottom up by adding ingredients to the sheet one at a time.

Each array has dozens of compounds arranged in grids of dots that are about the size of a pencil eraser.

They put each array up against a battery of germs, testing the potency of each compound against various bacterial strains.

The whole process of building and testing a batch of 50 to 300 compounds takes about two days.
Only about 2 percent of the compounds tested using the arrays show any potential against bacteria. And that's just a first step on a long path to drug development.

The next stage is to understand how the compounds work to kill bacteria. "What features of compounds are necessary for activity, and can we improve them?" Blackwell said.

Once the active elements and mechanism are understood, researchers can begin testing doses and evaluating the compounds for safety in animals and eventually humans, if trials go well.

The key is that with the new macroarray, Blackwell said it's possible to see which molecules are active fairly quickly, and "we can gather information on how to improve them fairly quickly."

Seattlepi

Hydrates and solid-state reactivity: A survey of beta-lactam antibiotics.

Hydrates and solid-state reactivity: A survey of beta-lactam antibiotics.

J Pharm Sci. 2007 Apr 23

Hickey MB,
Peterson ML,
Manas ES,
Alvarez J,
Haeffner F,
Almarsson O.

TransForm Pharmaceuticals, Inc., 29 Hartwell Avenue, Lexington, Massachusetts 02421.

Crystalline hydrates of hydrolytically susceptible pharmaceuticals are commonly encountered, and are particularly prevalent in the beta-lactam class of antibiotics. In order to rationalize how the apparent chemical incompatibility between water and beta-lactams is reduced through crystallization, a review of the published literature and available structural information on the solid state stability was undertaken. A search in the CSD yielded a total of 32 crystal structures of water-containing beta-lactams which were examined and classified in terms of hydrogen-bonded networks.

In most cases the waters of hydration in the single crystal structures were found to fulfill structural roles and were not sufficiently close in proximity to react with the beta-lactam ring. Published data for the solid-state of several hydrates were also considered. In general, the stability data indicate high thermal stability for the crystalline hydrates. Moreover, even when water molecules are in appropriate proximity and orientation with respect to the beta-lactam moiety for a reaction to occur, the crystalline solids remain stable.

The use of the crystal structure information along with computational modeling suggests that a combination of proximal relationships, steric and mechanistic arguments can explain the observed solid-state stability of crystalline beta-lactam hydrates.

(c) 2007 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 96: 1090-1099, 2007.

PMID: 17455335 [PubMed - as supplied by publisher]

Sequential Therapy Beats Standard Therapy For Helicobacter Pylori

Sequential Therapy Beats Standard Therapy For Helicobacter Pylori

Four antibiotics versus three

Main Category: GastroIntestinal / Gastroentorology News

Article Date: 19 Apr 2007 - 21:00 PDT

In a clinical trial testing two different ways to treat Helicobacter pylori infection (a common cause of stomach ulcers), researchers found that four antibiotics given sequentially cured the infection more often than standard treatment with three antibiotics taken together for 10 days (Article, p. 556). The cure rate for the sequential treatment was 91 percent compared to 71 percent for the standard treatment. The sequential regimen was also more effective than conventional therapy for patients with certain antibiotic-resistant H. pylori bacteria. (The article and editorial are published online. They will be available in the May 1, 2007, print edition of Annals of Internal Medicine.) Note: Annals of Internal Medicine is published by the American College of Physicians.

Dental Work and Antibiotics

Guidelines: Only Some Need Dental Antibiotics

Risks May Outweigh Benefits

POSTED: 9:46 am EDT April 20, 2007

Taking antibiotics before visiting the dentist may do more harm than good, the American Heart Association says.

Some dentists prescribe antibiotics before routine cleanings or extractions to prevent infective endocarditis, an infection of the heart's inner lining or valves. But the AHA now says that is only needed for people at high risk, such as those with artificial valves, a history of endocarditis or serious heart problems.

The doctor who led the work, Walter Wilson, said there is no evidence that the antibiotics prevent infection, and they may increase resistance of bacteria when infections do occur.

A news release said that everyday tooth brushing causes 154,000 times the risk of exposure to bacteria that could cause problems than having a tooth pulled.

Original Post

Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureus: Management Principles and Selection of Antibiotic Therapy.

Methicillin-Sensitive and Methicillin-Resistant Staphylococcus aureus: Management Principles and Selection of Antibiotic Therapy.
Dermatol Clin. 2007 Apr

Elston DM.
Department of Dermatology, Geisinger Medical Center, 100 North Academy Ave., Danville, PA 17822, USA; Department of Pathology, Geisinger Medical Center, 100 North Academy Ave., Danville, PA 17822, USA.

Strains of community-acquired Methicillin-resistant Staphylococcus aureus (CA-MRSA) have emerged as an important group of pathogens. Most infections present as cutaneous abscess and most of these may respond to drainage alone. Sulfonamide and tetracycline antibiotics remain valuable agents for most CA-MRSA infections, but inducible resistance to clindamycin is problematic in some areas. Linezolid, and the newer parenteral antibiotics should be reserved for serious infections.

PMID: 17430753 [PubMed - as supplied by publisher]