The Japanese journal of antibiotics最新文献

Arbekacin (ABK) is one of aminoglycosides which has indications for septicemia and pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) in Japan. ABK shows good clinical and microbiological efficacies also against Gram-negative bacteria (GNB), including Pseudomonas aeruginosa. In addition, furthermore, ABK would be sometimes effective also against antimicrobial-resistant GNB. We investigated ABK inhalation, which showed good pulmonary drug delivery, for the treatment of pneumonia caused by multidrug-resistant Gram-negative organisms and MRSA. Six patients with pneumonia were treated with ABK inhalation therapy (50 mg x three times/day). We observed clinical effect for multidrug-resistant organisms in 6/6 patients. Although routine use of aerosolized antibiotics might not be able to be recommended for multidrug-resistant organisms, we might be able to adopt the ABK inhalation therapy for pneumonia especially caused by multidrug-resistant Gram-negative organisms in some situations where systemic therapy alone might be failure or inadequate, or where intravenous access is not available because of systemic toxicity. Further studies would be needed for ABK inhalation therapy for pneumonia.

Human respiratory syncytial virus (RSV) is a major causative agent of respiratory infections. Common cold syndrome caused by RS virus, which is prevalent in winter, occasionally develops into bronchitis, bronchiolitis and pneumonia. In particular, severe RS virus infections in infants with underlying cardiopulmonary diseases and with low-birth weight baby have been a problem. Furthermore, repetitive RS virus infections occur for the entire lifetime, and the relationship between RS virus infections and exacerbation of COPD and bronchial asthma is also indicated mainly in elderly individuals. Various immunomodulatory effects other than antimicrobial activity of macrolides, including clarithromycin, have been reported, and their clinical usefulness is shown mainly in respiratory diseases. This review describes the findings of action of macrolides on RS virus infections.

Sitafloxacin (STFX, Gracevit 50 mg, fine granules 10%), an oral quinolone antibacterial agent, was approved additionally for administration at a dose of 100 mg once a day in August 2011. A use-results survey on STFX 100 mg/day was performed from December 2011 to May 2013. In total, 1,186 case cards were collected from 226 medical institutions and 1,089 cases were subjected to a safety evaluation and 1,069 were subjected to an efficacy evaluation. The incidence of adverse drug reactions (ADRs) was 2.11% (23/1,089 cases) and no serious ADRs were observed. The major ADR was diarrhea at 1.10% (12/1,089 cases). Of these 12 cases, 10 cases developed symptoms within 4 days of treatment. All of them, except one case that could not be followed up, either recovered or improved. Nonsteroidal anti-inflammatory drugs of the phenyl acetate and propionate types, which require caution when coadministered with STFX, were used concomitantly by 17.6% (192/1,089 cases) of patients but no central nervous system ADRs were observed. The overall efficacy rate was 96.4% (1,030/1,069 cases) and by types of infections, it was 97.0% (387/399 cases) for respiratory tract infections, 96.7% (353/365 cases) for urinary tract infections, 94.7% (36/38 cases) for gynecological infections, 92.3% (132/143 cases) for otorhinolaryngological infections, 98.4% (122/124 cases) for dental and oral surgical infections. The efficacy rate in every category of site of infection exceeded 90%. The overall eradication rate was 94.4% (185/196 strains) including Gram-positive bacteria at 95.4% (62/65 strains), Gram-negative bacteria at 92.2% (94/102 strains), anaerobes at 100.0% (11/11 strains) and atypical bacteria at 100.0% (18/18 strains). In conclusion, this use-results survey confirmed that STFX 100 mg/day is an effective administration with no serious problems in its safety profile and efficacy rate of over 90% in every category of site of infection.

In November 2004, "Guidelines for the Management of Respiratory Infectious Diseases in Children in Japan" was published ahead of the rest of the world, by Japanese Society of Pediatric Pulmonology/Japanese Society for Pediatric Infectious Diseases, based on the data on causative organisms in the lower respiratory tract. In its 2011 version, classification of the severity of pneumonia was renewed based on the latest information. As a result, many types of pneumonia in children are now classified as mild or moderate. This means that many patients who might have conventionally required hospital treatment can now be managed on an outpatient basis. The reason for realization of the wider range of outpatient treatment is the availability of two new oral antimicrobial agents, tebipenem pivoxil and tosufloxacin tosilate hydrate, for the treatment of infections in children. Analysis of data on medical expenses shows a decreased rate of hospitalization due to pneumonia year by year after launch of these two drugs, suggesting that these drugs have contributed to wider range of outpatient treatment. This manuscript discusses the effect of tebipenem pivoxil and tosufloxacin tosilate hydrate in the treatment of pneumonia.

Treatment for chronic pulmonary aspergillosis is difficult and frequently is required for prolong period. In outpatients setting, only voriconazole and itraconazole could be used. Since liposomal amphotericin B (L-AMB) demonstrated prolonged half-time, we have investigated the feasibility of L-AMB in outpatient setting. Three cases of chronic pulmonary aspergillosis were treated with intermittent administration of 2.5 mg/kg of L-AMB twice weekly for one month in outpatient settings. Improve of symptoms was attained in 2 of 3 cases. Improvement of chest images were in 2 of 3, improvement of laboratory test were in 2 of 3. Adverse events were only fatigue and short period of fever. No recurrence of pulmonary aspergillosis has been found after treatment. Intermittent administration of L-AMB in outpatient settings could be an option for pulmonary aspergillosis.

Azithromycin (AZM) is one of 15-membered rings macrolide antibiotics with wide spectrum of antimicrobial efficacy for Gram-positive and -negative bacteria and also atypical bacteria. So far, there had been no reports of the prospective studies evaluating efficacy and safety of AZM infusion in patients with mild or moderate community-acquired pneumonia (CAP). This study was conducted to evaluate prospectively the efficacy and safety of AZM in patients with mild or moderate CAP. AZM 500 mg was intravenously administered once daily, and the clinical efficacy were evaluated by clinical symptoms, peripheral blood laboratory findings and chest X-rays. Sixty-four patients were firstly registered, and eventually 61 and 62 patients were enrolled for the evaluation of clinical efficacy and safety of AZM, respectively. The efficacy of AZM in 61 patients evaluated was 88.5%. In addition, the efficacies of AZM in each pneumonia severity index by A-DROP system by the Japanese Respiratory Society (JRS) guideline in CAP were 85.2% in mild and 91.2% in moderate. Furthermore, the efficacy of AZM in each differentiation between suspicion of bacterial pneumonia and that of atypical pneumonia by JRS guideline in CAP were 91.7% in suspicion of atypical pneumonia, and its efficacy was high than that of bacterial pneumonia. Nineteen patients (20 cases; 15 with liver dysfunction, 4 with diarrhea, 1 with vascular pain) out of 62 patients were reported to have possible adverse effects of AZM. All of the patients with these adverse effects demonstrated mild dysfunction and continued AZM treatment, and these dysfunctions normalized soon after cessation of AZM. In conclusion, AZM is effective drug for patients with mild or moderate CAP, and we believe that it may be one of effective choice in the treatment of CAP patients who need hospitalization.

This in vitro study examined the combined effects of double antibacterial drugs against multidrug-resistant Pseudomonas aeruginosa (MDRP). The tested clinical isolates from Hiroshima University Hospital were 40 strains which met the criteria for MDRP, that is, the minimum inhibitory concentration (MIC) was > or = 16 microg/mL of meropenem, > or = 4 microg/mL of ciprofloxacin and > or = 32 microg/mL of amikacin. Using the original checkerboard plates for colistin (CL), arbekacin (ABK), aztreonam (AZT), rifampicin (RFP) and piperacillin (PIPC), MIC values were determined for single and double combinations. Based on the MIC values, fractional inhibitory concentration index values were calculated and the combined effects (synergy action or additive action) were evaluated. The three strongest drugs among the tested combinations were i) CL + RFP (synergy, 80.0%; additive, 17.5%), ii) RFP + ABK (synergy, 7.5%; additive, 70.0%) and iii) RFP + AZT (synergy, 5.0%; additive, 77.5%). In these cases, the arithmetic mean MIC value of each drug significantly decreased as follows: i) 1.38 microg/mL (alone) and 0.26 microg/mL (with RFP) for CL, 19.85 microg/mL (alone) and 1.85 microg/mL (with CL) for RFP; ii) 19.85 microg/mL (alone) and 7.53 microg/mL (with ABK) for RFP, 8.87 microg/mL (alone) and 2.79 microg/mL (with RFP) for ABK; iii) 19.85 microg/mL (alone) and 10.15 microg/mL (with AZT) for RFP, 28.3 microg/ mL (alone) and 6.65 microg/mL (with RFP) for AZT. Of 40 strains, metallo-beta-lactamase and aminoglycoside 6'-N-acetyltransferase were found in 20 and 37 strains, respectively; however, no significant influence of these factors was observed on the combined effects of i), ii) and iii). The results of this study provide an in vitro rationale for RFP plus CL, ABK or AZT as an effective combination therapy for MDRP infections, although the results should be verified and compared with other antibacterial drugs in further studies.

Background: Many case series studies have reported risk factors of infection with anaerobic bacteria, but few factor analysis studies have been conducted.

Objective: We conducted a case-control study to identify the risk factors of anaerobic bacteremia.

Methods: We compared a number of characteristics of patients with anaerobic bacteremia with those with aerobic bacteremia. Clinical information for 71 patients of anaerobic bacteremia was collected from January 1999 to December 2012 in Aichi Medical University Hospital. For each case, we identified up to four controls matched by the time of the positive blood culture.

Results: Multivariate logistic analyses revealed an association between anaerobic bacteremia and malignancy (OR: 3.35, 95% CI: 1.85-6.09), Douglas' pouch drains (OR: 25.90, 95% CI: 2.90-25.00) and chest drains (OR: 3.35, 95% CI: 1.19-9.43) as the primary causative disease, as well as associations between anaerobic bacteremia and the gastrointestinal tract (OR: 3.29, 95% CI: 1.38-7.81), genitourinary tract (OR: 4.98, 95% CI: 2.06-12.05), Douglas' pouch drains (OR: 16.95, 95% CI: 1.82-166.67) and chest drains (OR: 3.62, 95% CI: 1.29-10.20) as the primary causative organs. On the other hand, our study showed that having a central venous catheter was not associated with anaerobic bacteremia.

Conclusions: We demonstrated an association between anaerobic bacteremia and malignancy, gastrointestinal and genitourinary tracts, patients having a Douglas' pouch drains or chest drains. These findings may be useful for developing early appropriate management for anaerobic bacteremia.

Latamoxef (LMOX, Moxalactam) is one of the beta-lactam antibiotics which is stable against beta-lactamase. In this study, the antibacterial activity of LMOX was investigated, and Monte Carlo simulation was conducted to determine the appropriate dosing regimens of LMOX against extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae. The probability of target attainment (PTA) was analyzed at 40% and 70% of time above minimum inhibitory concentration (MIC) (time above MIC, T(>MIC)) for bacteriostatic and bactericidal effect respectively. All the tested regimens achieved 85% of PTA at 40% of T(>MIC) against ESBL producing Escherichia coli, and all the tested regimens except 1g q12h with 1 hour infusion achieved 85% of PTA at 40% of T(>MIC) against ESBL producing Klebsiella pneumoniae. The effective regimens to achieve 85% of PTA at 70% of T(>MIC )against E. coli were lg ql2h with 4 hours infusion, lg q8h with 1-4 hours infusion, 2g ql2h with 2-4 hours infusion, and lg q6h with 1-4 hours infusion. The effective regimens to achieve 85% of PTA at 70% of T(>MIC) against K. pneumoniae were 1g q8h with 3-4 hours infusion and 1g q6h with 1-4 hours infusion. These results of pharmacokinetics/pharmacodynamics (PK/PD) modeling showed the potent efficacy of LMOX against bacterial infections caused by ESBL producing Enterobacteriaceae.