PubMed Health⌕ Search

Biomedical subjects

Thomas M File

Publications and source records attributed to Thomas M File.

43 records · Page 3Linked to original sources
PubMed2002

Appropriate use of antimicrobials for drug-resistant pneumonia: focus on the significance of beta-lactam-resistant Streptococcus pneumoniae.

The beta-lactam antibiotics (penicillins and cephalosporins) are commonly prescribed for the treatment of community-acquired pneumonia. However, Streptococcus pneumoniae, the most common etiologic agent of community-acquired pneumonia, has become increasingly resistant to beta-lactams over the past decade. The results of several studies suggest that penicillins remain effective for streptococcal pneumonia when the infecting pathogen has a minimal inhibitory concentration (MIC) </=2 microgram/mL, presumably because the pharmacokinetic and pharmacodynamic parameters associated with current dosing regimens are still sufficient. However, when the MIC >/=4 microgram/mL, increased rates of mortality (for patients who survive their first 4 days of hospitalization) may occur. Currently, 3.5%-7.8% of S. pneumoniae clinical isolates have MICs that fall in this latter class, but these rates may rise in the future. The clinical relevance of in vitro resistance may be related to at least 3 factors: concordance of antimicrobial therapy, severity of illness, and virulence.

Contraindications↗
PubMed2002

Oral gemifloxacin versus sequential therapy with intravenous ceftriaxone/oral cefuroxime with or without a macrolide in the treatment of patients hospitalized with community-acquired pneumonia: a randomized, open-label, multicenter study of clinical efficacy and tolerability.

OBJECTIVE: This study aimed to compare the efficacy and safety of oral gemifloxacin, an enhanced-affinity quinolone, with sequential therapy with IV ceftriaxone followed by oral cefuroxime (with or without a macrolide) in patients hospitalized for community-acquired pneumonia (CAP). METHODS: A randomized, open-label, multicenter study comprised adults hospitalized with a clinical and radiologic diagnosis of CAP. Patients were randomized 1:1 to receive either (1) oral gemifloxacin 320 mg once daily (7-14 days); or (2) IV ceftriaxone 2 g once daily (1-7 days) followed by oral cefuroxime 500 mg twice daily (1-13 days) for a total of < or = 14 days. Patients receiving ceftriaxone/cefuroxime were allowed concomitant macrolide treatment. RESULTS: A total of 345 patients were randomized, of whom 341 received at least 1 dose of study medication (gemifloxacin, 169/172; ceftriaxone/cefuroxime, 172/173). Clinical success rates in the clinically evaluable (CE) population at follow-up (day 21-28 post-therapy), the primary end point, were 92.2% (107/116) for gemifloxacin and 93.4% (113/121) for ceftriaxone/cefuroxime (treatment difference, -1.15; 95% CI, -7.73 to 5.43). In patients in Fine risk classes IV and V, the clinical success rate was 87.0% (20/23) for gemifloxacin versus 83.3% (20/24) for ceftriaxone/cefuroxime. No difference in clinical response at follow-up was noted based on macrolide use. Bacteriologic success rates at follow-up in the bacteriologically evaluable (BE) population were 90.6% (58/64) for gemifloxacin and 87.3% (55/63) for ceftriaxone/cefuroxime (treatment difference 3.32; 95% CI, -7.57 to 14.21). The clinical success rate in bacteremic patients at follow-up (BE population) was 100.0%. Both treatments were generally well tolerated. The frequency and types of adverse events were similar between the 2 groups. The most common treatment-related adverse events with gemifloxacin were diarrhea, liver-function adverse events, and rash; with ceftriaxone/cefuroxime, they were diarrhea, elevated hepatic-enzyme activity, and moniliasis. CONCLUSION: The clinical efficacy and tolerability of oral gemifloxacin 320 mg once daily were similar to those of IV ceftriaxone followed by oral cefuroxime (with or without a macrolide) in the treatment of adult patients hospitalized with moderate to severe CAP. Both treatments were effective in bacteremic patients and those at increased risk of mortality.

Administration, Oral↗
PubMed2002

Outcome of treatment of respiratory tract infections due to Streptococcus pneumoniae, including drug-resistant strains, with pharmacokinetically enhanced amoxycillin/clavulanate.

The efficacy of a new pharmacokinetically enhanced formulation of amoxycillin/clavulanate (AMX/CA) 2000/125 mg, twice daily, designed to provide adequate levels of amoxycillin over the 12-h dosing interval to eradicate penicillin-resistant Streptococcus pneumoniae (PRSP) with amoxycillin (+/-clavulanic acid) MICs of </=4 mg/l, was evaluated in patients with respiratory infections caused by S. pneumoniae, including PRSP (penicillin MICs 2-16 mg/l). Data from nine clinical studies were combined (total intent-to-treat N=5531). Six randomized, double-blind studies used levofloxacin 500 mg od in acute bacterial sinusitis (ABS), levofloxacin 500 mg od in acute exacerbations of chronic bronchitis (AECB), clarithromycin 500 mg bid in AECB, AMX/CA 875/125 mg bid and tid in community-acquired pneumonia (CAP) and AMX/CA 1000/125 mg tid in CAP as comparators. The three remaining studies (two in ABS and one in CAP) were non-comparative. In the AMX/CA 2000/125 mg bid-treated patients evaluable at follow-up (Day 14-39), outcome was successful in 60/64 (93.7%) patients with S. pneumoniae infections in the comparative studies and 348/363 (95.9%) in the non-comparative studies, including 95.6% of all patients and 95.2% of patients whose isolates had AMX/CA MICs of >/=4 mg/l. In the pooled comparator group, the success rate at follow-up was 86.5% (45/52). For PRSP (AMX/CA MICs of 0.5-8 mg/l), the overall success rate was 98.2% (55/56) at follow-up for AMX/CA 2000/125 mg and 50.0% (2/4) for comparators. AMX/CA 2000/125 mg shows efficacy comparable to that of the comparators evaluated against S. pneumoniae infections. Due to its favorable pharmacokinetic/pharmacodynamic profile and promising clinical success, the new AMX/CA 2000/125 mg formulation should be considered for the empirical treatment of respiratory tract infections in regions with a high prevalence of antimicrobial-resistant S. pneumoniae and in patients at high risk of antimicrobial-resistant S. pneumoniae infection as this formulation covers many PRSP that are non-susceptible to amoxycillin (+/-clavulanic acid) (MICs of >/=4 mg/l) as well as common beta-lactamase-producing respiratory pathogens.

Adolescent↗
PubMed2002

Clinical and public health implications of macrolide-resistant Streptococcus pneumoniae.

Macrolide resistance among Streptococcus pneumoniae is a growing global concern, although its specific impact on public health is not currently well defined. A Consensus Working Group was convened in March 2001 to address whether credible, scientific data substantiate macrolide resistance in S. pneumoniae as: (i) producing significant morbidity; (ii) creating attendant health and economic burdens; (iii) constituting a public health threat; and (iv) warranting intervention, including development of new antibiotics with efficacy against these strains. Despite the limitations of available clinical data, concern about the possibility of treatment failure with macrolides is being expressed in clinical practice and in formal treatment guidelines, threatening the important role of these agents in the treatment of respiratory tract infections. Further studies are required to monitor and control macrolide resistance and evaluate settings in which macrolide treatment failures are occurring, and new therapeutic interventions are needed.

Adolescent↗
PubMed2002

Etiology and management of community-acquired pneumonia in Asia.

The causative organisms of community-acquired pneumonia, especially in Japan and Korea, are essentially similar to those in Western countries. If there are any differences, these are due to the laboratory tests and criteria used to define pathogenicity. Overall, Streptococcus pneumoniae is the most frequently occurring pathogen and Haemophilus influenzae, Mycoplasma pneumoniae, Chlamydia pneumoniae and viruses follow. Legionella spp. look likely to be low frequency pathogens in Asian countries, but a reason for this might be limitations of the laboratory tests used. A high frequency of Gram-negative bacilli as pathogens of community-acquired pneumonia in some Asian countries may be due to different criteria used to identify disease-causing organisms. A small number of papers about antibiotic resistance have shown no large differences between Asian countries, but considerable differences to Western countries, such as frequency of macrolide-resistant S. pneumoniae. Some Asian countries have their own guidelines for community-acquired pneumonia, but these are written in their own languages.

Asia↗
PubMed2002

Rational use of antibiotics to treat respiratory tract infections.

OBJECTIVES: To foster the appropriate use of antimicrobial agents for respiratory tract infections and to review factors that should help achieve this objective. STUDY DESIGN: Review of evidence-based guidelines and recommendations for proper antibiotic drug use for respiratory tract infections. RESULTS AND CONCLUSIONS: Antibiotic drug overuse and inappropriate antibiotic drug selection are associated with increased drug resistance among respiratory pathogens (most notably, Streptococcus pneumoniae), possible progression to chronic disease, and increased treatment costs. Awareness of clinical manifestations that help differentiate viral from bacterial infection and the use of guidelines can promote the appropriate management of respiratory tract infections. Community-acquired pneumonia, acute bacterial rhinosinusitis, and selected cases of acute exacerbations of chronic bronchitis (50%) warrant antimicrobial therapy, whereas otitis media with effusion, acute bronchitis, and most rhinosinusitis are viral and do not require antibiotic therapy.

Anti-Bacterial Agents↗