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Thomas M File

Publications and source records attributed to Thomas M File.

At least 19 recordsLinked to original sources
PubMed2006

Prevalence and antibacterial susceptibility of mef(A)-positive macrolide-resistant Streptococcus pneumoniae over 4 years (2000 to 2004) of the PROTEKT US Study.

In the United States, approximately 30% of Streptococcus pneumoniae isolates are macrolide (erythromycin [ERY]) resistant (ERSP), most commonly due to expression of the mef(A) gene previously associated with lower-level ERY resistance (ERYr; MIC=1 to 4 microg/ml). The data from the PROTEKT US surveillance study were analyzed to evaluate the prevalence and antibacterial susceptibility of mef(A)-positive ERSP. In all, 26,634 isolates of S. pneumoniae were collected in the United States between 2000 and 2004 from centers common to all years. ERYr was stable at approximately 29% over the 4 years, but the proportion of ERSP isolates positive for mef(A) alone decreased (year 1 [2000 to 2001], 69.0%; year 4 [2003 to 2004], 60.7%), with the sharpest declines seen in isolates from patients from 0 to 2 years of age. Conversely, the proportion isolates positive for both erm(B) and mef(A) increased over the duration of the present study (year 1, 9.3%; year 4, 19.1%), a change that was again most marked in patients aged <or=2 years. The majority of ERSP isolates expressing mef(A) alone exhibited higher than previously reported levels of ERYr (MIC90=16 microg/ml). However, the ketolide antibacterial telithromycin consistently demonstrated in vitro activity against these isolates over the 4 years of the study (MIC90=0.5 to 1 microg/ml).

Anti-Bacterial Agents↗
PubMed2006

Ventilator-associated pneumonia: gearing towards shorter-course therapy.

PURPOSE OF REVIEW: The studies that are reviewed in this article have all concluded that a shorter duration of antibiotic therapy (7-8 days) may be adequate in the treatment of the majority of patients with ventilator-associated pneumonia, and does not confer an increased incidence of mortality. RECENT FINDINGS: Ventilator-associated pneumonia has traditionally been treated with at least 2 weeks of antimicrobial therapy. With the increasing emergence of multi-drug-resistant pathogens, however, efforts have been directed at minimizing the duration of therapy. Several studies have emerged over the last few years aiming to shorten the duration of antimicrobial therapy for ventilator-associated pneumonia. SUMMARY: The minimum effective duration of antibiotic therapy, however, remains unclear. Further studies geared towards determining this are needed.

Anti-Bacterial Agents↗
PubMed2006

Levofloxacin for the treatment of community-acquired pneumonia.

New respiratory fluoroquinolones (FQs), such as levofloxacin, offer many improved qualities over older agents, such as ciprofloxacin. These include retaining excellent Gram-negative bacilli activity, with improved Gram-positive activity. New FQ-like levofloxacin possesses greater bioavailabilty and a longer serum half-life compared with ciprofloxacin, allowing for once-daily dosing, which may improve patient adherence. The high bioavailability of levofloxacin allows for rapid step-down from intravenous administration to oral therapy, minimizing unnecessary hospitalization, which may decrease costs and improve patient quality of life. Levofloxacin has been evaluated for the treatment of community-acquired pneumonia (CAP) in numerous randomized clinical trials. Most published studies have used the 500 mg dose, although more recent studies have investigated the 750 mg dose once daily. These trials demonstrate that levofloxacin is effective and safe for the treatment of CAP, displaying relatively mild adverse effects that are more or less comparable with ciprofloxacin. Levofloxacin has much to offer in terms of bacterial eradication, including for resistant respiratory pathogens. However, ciprofloxacin-resistant organisms are becoming more prevalent so prudence must be exercised when prescribing this agent.

Community-Acquired Infections↗
PubMed2005

A clinician's guide to the appropriate and accurate use of antibiotics: the Council for Appropriate and Rational Antibiotic Therapy (CARAT) criteria.

In response to the overuse and misuse of antibiotics, leading to increasing bacterial resistance and decreasing development of new antibiotics, the Council for Appropriate and Rational Antibiotic Therapy (CARAT) has developed criteria to guide appropriate and accurate antibiotic selection. The criteria, which are aimed at optimizing antibiotic therapy, include evidence-based results, therapeutic benefits, safety, optimal drug for the optimal duration, and cost-effectiveness.

Anti-Bacterial Agents↗
PubMed2005

Efficacy of a new pharmacokinetically enhanced formulation of amoxicillin/clavulanate (2000/125 mg) in adults with community-acquired pneumonia caused by Streptococcus pneumoniae, including penicillin-resistant strains.

Community-acquired pneumonia (CAP) is a common respiratory illness, frequently caused by Streptococcus pneumoniae. The prevalence of S. pneumoniae resistance to common antimicrobials has increased over recent years. A new pharmacokinetically enhanced formulation of amoxicillin/clavulanate (2000/125 mg) has been developed, designed to combat infections caused by S. pneumoniae, including penicillin-resistant (PRSP, penicillin minimum inhibitory concentrations (MICs) >or=2mg/l) isolates, and those with elevated amoxicillin/clavulanic acid MICs, while maintaining coverage of beta-lactamase-producing pathogens. A pooled efficacy analysis of four randomized (1:1) and one non-comparative clinical trials of amoxicillin/clavulanate, 2000/125 mg, given twice daily, was conducted in adult patients with CAP. Comparator agents were conventional amoxicillin/clavulanate formulations. At follow-up (days 16-39), efficacy (eradication of the initial pathogen or clinical cure in patients for whom no repeat culture was performed) in patients with S. pneumoniae infection was 92.3% (274/297) for amoxicillin/clavulanate, 2000/125 mg and 85.2% (46/54) for comparators (P=0.11). Twenty-four of 25 PRSP-infected patients receiving amoxicillin/clavulanate, 2000/125 mg were treated successfully. Both amoxicillin/clavulanate, 2000/125 mg and comparators were well tolerated, with few patients withdrawing from the studies.

Adolescent↗
PubMed2005

Telithromycin new product overview.

Community-acquired respiratory tract infections (CARTIs), including community-acquired pneumonia, acute exacerbations of chronic bronchitis, and acute bacterial sinusitis, contribute substantially to health care costs in the United States. Although many prescriptions for antibiotics are written each year for the treatment of CARTIs, most are prescribed on an empiric basis. Concerns about the increasing prevalence of antimicrobial resistance and the changing pattern of pathogens isolated from subjects with CARTIs have raised questions about the empiric treatment paradigm. When choosing appropriate antimicrobial therapy for CARTIs, physicians must consider not only the spectrum of activity of antibiotics but also the potential risk of resistance. Telithromycin is the first member of the ketolide class, a new family of antimicrobials structurally related to the macrolides, to be approved by the US Food and Drug Administration for the treatment of CARTIs. The spectrum of activity of telithromycin includes common typical and atypical causative pathogens associated with community-acquired respiratory tract infections, including antibiotic-resistant strains of Streptococcus pneumoniae. Clinical trials have shown that telithromycin is as effective as traditionally used antimicrobial agents in the treatment of mild-to-moderate community-acquired pneumonia, acute exacerbations of chronic bronchitis, and acute bacterial sinusitis.

Anti-Bacterial Agents↗
PubMed2005

Meropenem versus imipenem-cilastatin for the treatment of hospitalized patients with complicated skin and skin structure infections: results of a multicenter, randomized, double-blind comparative study.

BACKGROUND: Meropenem, a broad-spectrum carbapenem with potent in vitro activity, is postulated to be an effective monotherapy for the treatment of complicated skin and skin structure infections (cSSSI). METHODS: This multicenter, international, double-blind, randomized, prospective study of hospitalized patients with cSSSI evaluated the efficacy, safety, and tolerability of meropenem (500 mg IV q8h) versus imipenem-cilastatin (500 mg IV q8h). The primary efficacy endpoint was clinical outcome at follow-up in the clinically evaluable (CE) and modified intent-to-treat populations (MITT; patients who met eligibility criteria and received at least one dose of study drug). The study aimed to demonstrate non-inferiority (delta of 10%, 95% confidence intervals) in clinical response in the CE population. Clinical responses for all pathogens at follow-up were assessed in the fully evaluable population (CE population with baseline pathogen and follow-up cultures). RESULTS: In total, 1,076 patients were enrolled. Of these, 692 patients comprised the MITT population (334 and 358 patients randomized to meropenem and imipenem-cilastatin, respectively) and 548 the CE population (261 and 287 patients randomized to meropenem and imipenem-cilastatin, respectively). Cure rates were 86.2% (meropenem) and 82.9% (imipenemcilastatin; 95% CI, -2.8, 9.3) in the CE population and 73.1% (meropenem) and 74.9% (imipenem-cilastatin; 95% CI, -8.4, 4.7) in the MITT population. The frequencies of adverse events and drug-related adverse events were similar between treatment groups. CONCLUSION: In one of the largest studies conducted to date of hospitalized patients with cSSSI, meropenem, 500 mg IV q8h had comparable safety and efficacy to imipenem-cilastatin, 500 mg IV q8h.

Adolescent↗
PubMed2005

Solutions to the problem of bacterial resistance.

The recent increase in bacterial resistance has been, and continues to be, unmatched by drug discovery and development. The judicious use of antibacterials must be observed so as to contain bacterial resistance and maintain the utility of agents currently on the market. Appropriate antibacterial use involves antibacterial avoidance when not indicated. When indicated, appropriate antibacterial use dictates that the optimal drug, dose and duration be utilized. Professional society guidelines facilitate drug selection as well as outline diagnostic criteria and important considerations for patient stratification. Pharmacodynamics is also key for drug selection and often guides determination of not only the optimal drug but also the optimal dose and duration. Importantly, bacterial eradication is essential, as it will reduce clinical failure, recurrence, or relapse and prevent the selection of resistance. Additional strategies to influence antibacterial prescribing and use such as formal continuing medical education, printed educational materials, better diagnostic tests, and vaccination contribute to the efforts to minimize bacterial resistance and are also addressed.

Anti-Bacterial Agents↗
PubMed2005

Severe acute respiratory syndrome: pertinent clinical characteristics and therapy.

Severe acute respiratory syndrome (SARS) is a newly emerged infection that is caused by a previously unrecognized virus - a novel coronavirus designated as SARS-associated coronavirus (SARS-CoV). From November 2002 to July 2003 the cumulative number of worldwide cases was >8000, with a mortality rate of close to 10%. The mortality has been higher in older patients and those with co-morbidities. SARS has been defined using clinical and epidemiological criteria and cases are considered laboratory-confirmed if SARS coronavirus is isolated, if antibody to SARS coronavirus is detected, or a polymerase chain reaction test by appropriate criteria is positive. At the time of writing (24 May 2004), no specific therapy has been recommended. A variety of treatments have been attempted, but there are no controlled data. Most patients have been treated throughout the illness with broad-spectrum antimicrobials, supplemental oxygen, intravenous fluids, and other supportive measures. Transmission of SARS is facilitated by close contact with patients with symptomatic infection. The majority of cases have been reported among healthcare providers and family members of SARS patients. Since SARS-CoV is contagious, measures for prevention center on avoidance of exposure, and infection control strategies for suspected cases and contacts. This includes standard precautions (hand hygiene), contact precautions (gowns, goggles, gloves) and airborne precautions (negative pressure rooms and high efficiency masks). In light of reports of new cases identified during the winter of 2003-4 in China, it seems possible that SARS will be an important cause of pneumonia in the future, and the screening of outpatients at risk for SARS may become part of the pneumonia evaluation.

Algorithms↗
PubMed2004

Clinical efficacy of newer agents in short-duration therapy for community-acquired pneumonia.

Streptococcus pneumoniae, the most important respiratory tract pathogen implicated in community-acquired pneumonia (CAP), is becoming increasingly resistant in vitro to the beta -lactams and macrolides, and fluoroquinolone resistance has been detected. A growing body of evidence suggests that prolonged antimicrobial use may contribute directly and indirectly to increased antimicrobial resistance among common respiratory pathogens. Long-term exposure to antimicrobial agents, especially less-potent agents, directly increases selection pressure for resistance. Indirectly, poor patient compliance, multiple daily dosing, and the increased risk of adverse events further complicate the resistance issue and diminish the efficacy of long-term antimicrobial use. Controlled clinical trials addressing the appropriate duration of therapy for CAP are lacking. However, available data suggest that with appropriate antibiotic selection, based on appropriate spectrum, potency, and pharmacokinetic/pharmacodynamic profile, lower respiratory tract infections in outpatients can be successfully treated in <7 days rather than the 7-14 days currently recommended.

Anti-Infective Agents↗
PubMed2004

Streptococcus pneumoniae and community-acquired pneumonia: a cause for concern.

Community-acquired pneumonia (CAP) is the sixth most common cause of death in the United States and the leading cause of death from infectious diseases. It is associated with significant morbidity and mortality, and poses a major economic burden to the healthcare system. Streptococcus pneumoniae is the leading cause of CAP. Other common bacterial causes include Haemophilus influenzae as well as atypical bacteria (Mycoplasma pneumoniae, Chlamydia pneumoniae, and Legionella species). Increasing resistance to a variety of antimicrobial agents has been documented in S. pneumoniae and is common in H. influenzae as well. Successful empiric therapy is paramount to the management of CAP to avoid treatment failure and subsequent associated costs. Given that resistance is increasing among respiratory pathogens, and S. pneumoniae is the most common etiologic agent identified in CAP, strategies for antimicrobial therapy should be based on the likely causative pathogen, the presence of risk factors for infection with resistant bacteria, and local resistance patterns.

Age Distribution↗
PubMed2004

Lack of recurrence of hyperlactatemia in HIV-infected patients switched from stavudine to abacavir or zidovudine.

Stavudine (d4T) has been observed in clinical trials and cohort studies to be more often implicated in cases of hyperlactatemia than other nucleoside reverse transcriptase inhibitors, possibly because of its relatively greater propensity to induce mitochondrial toxicity. The ESS40010 study was a 48-week, open-label, switch study that assessed changes in serum lactate levels and signs/symptoms of hyperlactatemia after substitution of abacavir (n = 86) or zidovudine (n = 32) for d4T in 118 virologically suppressed HIV-infected patients (HIV-1 RNA <400 copies/mL) who had developed serum lactate concentrations > or =2.2 mmol/L (n = 16) or had remained normolactatemic (n = 102) after receiving > or =6 months of d4T-based treatment. Median serum lactate decreased significantly below baseline at week 24 (-0.15 mmol/L, P = 0.0002) and week 48 (-0.15 mmol/L, P = 0.0015). In 10 hyperlactatemic patients in whom d4T was discontinued, serum HIV-1 RNA levels rebounded over the ensuing 31 days, but virologic suppression (HIV-1 RNA <400 copies/mL) was regained when treatment using abacavir or zidovudine was subsequently instituted. In the group with elevated lactate at baseline, symptoms of hyperlactatemia improved in 8% to 23% of patients, did not change in 69%, and worsened in 8%. Serum transaminases, which had been elevated while patients received d4T, normalized after d4T discontinuation and remained in the normal range after the switch to abacavir or zidovudine. Overall, in patients with d4T-associated hyperlactatemia, stopping d4T results in normalization of lactate and a rebound in viral load; restarting treatment using abacavir or zidovudine subsequently maintains normal lactate levels and rapidly leads to a return of virologic suppression.

Adult↗
PubMed2004

Evolution of amoxicillin/clavulanate in the treatment of adults with acute bacterial rhinosinusitis and community-acquired pneumonia in response to antimicrobial-resistance patterns.

Current treatment guidelines for community-acquired respiratory tract infections no longer depend solely on the characteristics of the patient and the clinical syndrome, but on those of the offending pathogen, including presence and level of antimicrobial resistance. The most common respiratory tract pathogens known to cause acute bacterial rhinosinusitis (ABRS) and community-acquired pneumonia (CAP) include Streptococcus pneumoniae and Haemophilus influenzae. The prevalence of antimicrobial resistance, especially b-lactum and macrolide resistance, among S pneumoniae and H influenzae has increased dramatically during the past 2 decades, diminishing the activity of many older antimicrobials against resistant organisms. A pharmacokinetically enhanced formulation of amoxicillin/clavulanate has been developed to fulfill the need for an oral b-lactam antimicrobial that achieves a greater time that the serum drug concentration exceeds the minimum inhibitory concentration (T > MIC) of antimicrobials against pathogens than conventional formulations to improve activity against S pneumoniae with reduced susceptibility to penicillin. The b-lactamase inhibitor clavulanate allows for coverage of b-lactamase-producing pathogens, such as H influenzae and M catarrhalis. This article reviews the rationale for, and evolution of, oral amoxicillin clavulanate for ABRS and CAP

Amoxicillin-Potassium Clavulanate Combination↗