Saturday, June 30, 2007

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

Sunday, June 24, 2007

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.


Monday, June 18, 2007

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,

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]

Tuesday, June 12, 2007

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

Sunday, June 10, 2007

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]

Saturday, June 02, 2007

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]