This study evaluated the in vitro activity of combinations of doripenem (DRPM) with aminoglycosides (tobramycin or amikacin) or fluoroquinolone (ciprofloxacin) against 92 isolates of Pseudomonas aeruginosa from 16 clinical facilities in 2004 in Japan. We also tested combination effect of other carbapenems (imipenem (IPM), meropenem, biapenem) with aminoglycosides or fluoroquinolone by checkerboard dilution methods. DRPM showed synergistic or additive effects with the aminoglycosides or the fluoroquinolone against 90% of the isolates. The combination of DRPM and aminoglycosides showed the strongest synergistic effects against IPM-intermediate resistant and IPM resistant strains among the tested combinations. These results suggested that combination of DRPM with aminoglycosides would be useful for the treatment of infections caused by P. aeruginosa including IPM-resistant strains.

The clinical efficacy and safety of levofloxacin (LVFX) 500 mg qd were evaluated in female patients with cervicitis with Chlamydia trachomatis and intrauterine infections. LVFX was administered orally at 500mg qd for 7 days.

Bacteriological efficacy was 94.4% (17/18) and clinical efficacy was 100% (16/16) at 14 to 21 days after the end of treatment in cervicitis. On the other hand, bacteriological efficacy and clinical efficacy at the end of treatment in intrauterine infections were 68.8% (11/16) and 94.7% (18/19), respectively. For safety, adverse drug reactions occurred in 9 of 43 patients (20.9%), i.e., increased ɣ-GTP in 2 patients, glucose urine present in 2, and each of all other adverse reactions occurred in 1. All adverse drug reactions observed were either mild or moderate.

Results suggested that LVFX 500mg qd was effective and safe in the treatment of cervicitis with Chlamydia trachomatis and intrauterine infections.

Using 49 clinical methicillin-susceptible Staphylococcus aureus isolates (MSSA) and 54 clinical methicillin-resistant Staphylococcus aureus (MRSA) isolates, we examined the change of MIC using five different inocula (2.5～4x10² cfu/spot～2.5～4x10⁶ cfu/spot). We found the big change of the MIC with the increase of the inoculum size in ampicillin against MSSA, and the change was small in cefazolin, meropenem, ciprofloxacin. For anti-MRSA antibiotics, we found the small change with the increase of the inoculums size in vancomycin and arbekacin, and the middle change in teicoplanin and linezolid against MSSA and MRSA.

The data from this study suggest that in serious and high inocula infections caused by S. aureus, the presence of an inoculum effect should be considered in curing.

We reported a case of meningitis caused by group B Streptococcus treated with high dose of meropenem (MEPM). A 67-year-old male was suffering from lumbago, fever up, vomiting and convulsion. He had received tumor resection of spinal cord at 40 years old. At the first consultation to our hospital, he had felt strong neck stiffness with Glasgow Coma Scale 5 (E1, V1, M3), and his body temperature was 37.0°C. His laboratory findings were as follows; white blood cell count 14600/𝜇L, C-reactive protein 4.39mg/dL, and marked elevation of the cell count in the cerebrospinal fluid. We had administered high dose of meropenem, 6g/day, and also vancomycin (VCM) on therapeutic drug monitoring. Since his clinical symptoms and laboratory findings had not shown adequate response after 4 days later, we had changed VCM to linezolid 1200mg/day, and had also continued MEPM, which had resulted in prompt resolution of the clinical symptoms and laboratory findings. Microbiological examination for cerebrospinal fluid has yielded a growth of serotype III group B Streptococcus (Streptococcus agalactiae). Since there have been few data on 6g/day MEPM against meningitis in spite of recommendation in several guidelines, further studies would be necessary including pharmacokinetic-pharmacodynamic analysis.

We investigated the relation between hospital antimirobial use density (AUD) and minimum in- hibitory concentrations (MIC) for Pseudomonas aeruginosa in four community hospitals. Subjects were a total of 476 strains isolated from urine, sputum, and pus during a total of seven years since 2002, for which 50- and 90-percentile MICs were analyzed. Hospitals A, B, and C moved in 2000, 2005, and 2009, respectively, but MIC₅₀ and MIC₉₀ were stable. MIC values showed significance in five drugs, in which Hospital B showed maximal values in five and Hospital D showed minimal val- ues in four drugs. AUD values were different in nine drugs, Hospital B showing the highest data in meropenem, flomoxef, and sulbactam/cefoperazone while Hospital D having the lowest data in meropenem, ceftazidime, cefotaxime, and sulbactam/cefoperazone. Thus MIC for P. aeruginosa may show resistance in the presence of high AUD with wide antimicrobial spectrum.