Moxifloxacin resistance and genotyping of Mycobacterium avium and Mycobacterium intracellulare isolates in Japan.

BACKGROUND: Although fluoroquinolones are considered as alternative therapies of pulmonary Mycobacterium avium complex (MAC) disease, the association between fluoroquinolone resistance and MAC genotypes in clinical isolates from individuals not previously treated for MAC infection is not fully clear. METHODS: Totals of 154 M. avium isolates and 35 Mycobacterium intracellulare isolates were obtained from treatment-naïve patients with pulmonary MAC disease at the diagnosis of MAC infection at 8 hospitals in Japan. Their susceptibilities of moxifloxacin were determined by broth microdilution methods. Moxifloxacin-resistant isolates were examined for mutations of gyrA and gyrB. Variable numbers of tandem repeats (VNTR) assay was performed using 15 M. avium VNTR loci and 16 M. intracellulare VNTR loci. RESULTS: Moxifloxacin susceptibility was categorized as resistant and intermediate for 6.5% and 16.9%, respectively, of M. avium isolates and 8.6% and 17.1% of M. intracellulare isolates. Although the isolates of both species had amino acid substitutions of Thr 96 and Thr 522 at the sites corresponding to Ser 95 in the M. tuberculosis GyrA and Gly 520 in the M. tuberculosis GyrB, respectively, these substitutions were observed irrespective of susceptibility and did not confer resistance. The VNTR assays showed revealed three clusters among M. avium isolates and two clusters among M. intracellulare isolates. No significant differences in moxifloxacin resistance were observed among these clusters. CONCLUSIONS: Although resistance or intermediate resistance to moxifloxacin was observed in approximately one-fourth of M. avium and M. intracellulare isolates, this resistance was not associated with mutations in gyrA and gyrB or with VNTR genotypes.

M ycobacterium abscessus pulmonary disease: individual patient data meta-analysis.

Treatment of Mycobacterium abscessus pulmonary disease (MAB-PD), caused by M. abscessus subsp. abscessus, M. abscessus subsp. massiliense or M. abscessus subsp. bolletii, is challenging.We conducted an individual patient data meta-analysis based on studies reporting treatment outcomes for MAB-PD to clarify treatment outcomes for MAB-PD and the impact of each drug on treatment outcomes. Treatment success was defined as culture conversion for ≥12 months while on treatment or sustained culture conversion without relapse until the end of treatment.Among 14 eligible studies, datasets from eight studies were provided and a total of 303 patients with MAB-PD were included in the analysis. The treatment success rate across all patients with MAB-PD was 45.6%. The specific treatment success rates were 33.0% for M. abscessus subsp. abscessus and 56.7% for M. abscessus subsp. massiliense For MAB-PD overall, the use of imipenem was associated with treatment success (adjusted odds ratio (aOR) 2.65, 95% CI 1.36-5.10). For patients with M. abscessus subsp. abscessus, the use of azithromycin (aOR 3.29, 95% CI 1.26-8.62), parenteral amikacin (aOR 1.44, 95% CI 1.05-1.99) or imipenem (aOR 7.96, 95% CI 1.52-41.6) was related to treatment success. For patients with M. abscessus subsp. massiliense, the choice among these drugs was not associated with treatment outcomes.Treatment outcomes for MAB-PD are unsatisfactory. The use of azithromycin, amikacin or imipenem was associated with better outcomes for patients with M. abscessus subsp. abscessus.

The efficacy, safety, and pharmacokinetics of biapenem administered thrice daily for the treatment of pneumonia in the elderly.

Biapenem has been widely used to treat bacterial pneumonia; however, there is little information concerning its efficacy and safety in elderly patients. Based on pharmacokinetic-pharmacodynamic theory, administration of biapenem thrice rather than twice daily would be expected to be more effective because of longer time above the minimum inhibitory concentration. In this study, we aimed to evaluate the efficacy, safety, and pharmacokinetics of biapenem (300 mg) administered thrice daily in pneumonic patients aged 65 years or older. Biapenem was effective in 22 of 25 patients, as assessed by the improvement in clinical symptoms and/or the eradication of the causative organisms, and caused no serious adverse events. The pharmacokinetic profile was established based on simulations using a modeling program. Among 17 patients whose causative organisms were detected, time above the minimum inhibitory concentration was estimated to be 100% in 16 patients, all of whom showed clinical improvement. The results of this study confirmed the efficacy and safety of 300 mg of biapenem administered thrice daily for the treatment of pneumonia in elderly patients.

Safety and efficacy of linezolid in 16 infants and children in Japan.

Linezolid, an oxazolidinone antibiotic, exhibits a broad spectrum of activity against Gram-positive bacteria. It has been licensed for adult use in Japan since 2006 for MRSA infections, and has also been used off-label for pediatric patients. At our university hospital, a total of 16 infants and children (including one non-Japanese Asian) were administered linezolid owing to infection with multidrug-resistant Gram-positive bacteria, after consent had been provided. All patients had severe underlying diseases or indications for surgery. Eighty-eight percent of the causal microorganisms were methicillin-resistant Staphylococcus aureus (MRSA) or methicillin-resistant coagulase-negative Staphylococcus and all were sensitive to linezolid. Linezolid was administered because the antecedent anti-MRSA medications were ineffective or contraindicated, or intravenous-to-oral switch therapy was requested owing to cardiac or orthopedic surgical-site infections. The median duration of administration was 13 days (range 3-31 days). The overall efficacy was 91 % (10/11) in those for whom efficacy could be evaluated. Only two patients (both teen-aged) encountered linezolid-related adverse effects (13 %, 2/16). One patient showed elevation of liver enzymes (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]), requiring that administration be withdrawn, but enzyme levels returned to normal after the patient had been switched to vancomycin. The other patient showed transiently decreased platelet counts. Linezolid is considered generally safe and effective for children in Japan, especially for those who cannot use other anti-MRSA medications or those who require oral antibiotics for infections with multidrug-resistant Gram-positive bacteria.