Antimicrobial susceptibility testing has been conducted continuously as post marketing surveillance of levofloxacin (LVFX) since 1994. The present survey was undertaken to investigate in vitro susceptibilities of bacteria to 33 selected antibacterial agents, focusing on fluoroquinolones (FQs), using 11,762 clinical isolates for 19 species collected from 69 centers during 2013 in Japan. The common respiratory pathogens Streptococcus pyogenes, Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae continue to show a high susceptibility to FQs, while the percentage of macrolide-resistant S. pneumoniae was markedly increased to around 80%. With H. influenzae, the percentage of β-lactamase-negative ampicillin resistant isolates had been increasing continuously from 2002, but no increase was observed from 2010 to 2013 (25.8% in 2002, 40.0% in 2004, 50.1% in 2007, 57.9% in 2010, and 57.1% in 2013). Most strains of Enterobacteriaceae showed a high susceptibility to FQs, but the isolation frequency of levofloxacin-resistant Escherichia coli including intermediate resistance was 34.4%, showing a continuous increase. Another Enterobacteriaceae member, Klebsiella pneumoniae, showed low resistance to FQs in contrast with E. coli. Regarding methicillin-resistant Staphylococcus aureus (MRSA), the percentage of FQ-susceptible isolates was low at 15.8–18.0%, with the exception of 55.3% susceptibility to sitafloxacin. On the other hand, methicillin susceptible S. aureus (MSSA) isolates showed high susceptibility to FQs, at 87.0–99.3%. With Enterococcus faecium, the percentage of FQ-susceptible isolates was 6.8-24.7%. The percentage of FQ-susceptible Pseudomonas aeruginosa was 83.4–89.3% among isolates derived from urinary tract infections (UTIs), while that from respiratory tract infections (RTIs) was 88.1–93.7%. This was summarized as susceptibility to FQs over 80% in both infections. A continuous decrease in FQ-resistant P. aeruginosa was noted, especially among isolates from UTIs. Regarding multidrug-resistant P. aeruginosa, the percentage has been decreasing continuously since 2007 and was 1.6% from UTIs and 0% from RTI in this survey. Acinetobacter spp. showed high susceptibility to FQs. The percentage of imipenem-resistant Acinetobacter spp. was 2.7% (14 isolates) and that of multidrug-resistant was 0.2% (1 isolate). In Neisseria gonorrhoeae, ceftriaxone (CTRX) had been showing 100% susceptibility until 2007, but CTRX-resistant strains have been detected in both 2010 and this survey. In conclusion, the resistance of methicillin-resistant staphylococci, E. faecium, N. gonorrhoeae, and E. coli to the FQs, which have been used clinically for over 20 years, was shown to be 30% or more (31.7–87.1%) in the present surveillance regarding susceptibility. These results were similar to those from previous surveillance, and no species that started to show significant resistance to FQs were identified in the present surveillance. Regarding other bacterial species, susceptibility to ciprofloxacin less than 80% was observed in some, while susceptibility to other FQs was maintained at a high level, at 80% or more.

Respiratory quinolones (RQs) are broad-spectrum antimicrobial agents used for the treatment of a wide variety of community-acquired and nosocomial infections. However, bacterial resistance to quinolones has been on the increase. In this study, we investigated the predicted efficacy of RQs for various strains of 9 bacterial species clinically isolated at our university hospital using the Monte Carlo simulation (MCS) method based on pharmacokinetics/pharmacodynamics modeling. In addition, the influence of the patients’ renal function on the efficacy of RQs was evaluated. We surveyed antimicrobial susceptibility testing of 9 bacterial species (n=number of strains) [Streptococcus pneumoniae (n=15), Streptococcus pyogenes (n=14), Streptococcus agalactiae (n=19), methicillin-susceptible Staphylococcus aureus (MSSA) (n=24), Escherichia coli (n=35), Haemophilus influenzae (n=17), Klebsiella pneumoniae (n=14), Pseudomonas aeruginosa (n=31), and Moraxella catarrhalis (n=11)] to 4 RQs [garenoxacin (GRNX), levofloxacin (LVFX), sitafloxacin (STFX), and moxifloxacin (MFLX)]. We found that compared with the other RQs, Gram-positive cocci was most resistant to LVFX, and that the minimum inhibitory concentration (MIC₉₀) values for S. pneumoniae, S. pyogenes, S. agalactiae, and MSSA were high (2, 16, >16, and 8 μg/mL, respectively). In regard to Gram-negative rods, the susceptibility of E. coli to RQs was found to be decreased, with the MIC₉₀ values of GRNX, LVFX, STFX, and MFLX being >16, 16, 1, and 16 μg/mL, respectively. MCS revealed that the target attainment rate of the area under the unbound concentration- time curve divided by the MIC₉₀ (f・AUC/MIC ratio), against S. pneumoniae was 86.9-100%, but against E. coli was low (52.1-66.2%). The f・AUC/MIC target attainment rate of LVFX against S. pneumoniae, S. pyogenes, and S. agalactiae tended to decrease due to increased creatinine clearance, and that of LVFX and STFX against MSSA also tended to decrease. The findings of this study suggest that the drug susceptibility distribution of each RQ varies, even within the same bacterial species, and that the expected efficacy also varies between the drugs. Moreover, the influence of the patient’s renal function on the efficacy differed among the 3 renal excretory drugs (GRNX, LVFX, and STFX), thus suggesting that the efficacy also differs. In conclusion, the findings of this study show that for the administration of RQs, it is desirable to select agents in consideration of surveyed sensitivity within the population and the pharmacokinetic characteristics.

A total of 473 strains of Enterobacteriaceae, including Escherichia coli, Klebsiella spp., Proteus spp., Citrobacter spp., Enterobacter spp., Serratia spp. and Providencia spp., were isolated from patients admitted to intensive care units and surgical units in Russia. About 90% of the isolates carried factors resistant to betalactams. The isolation rates of the extended-spectrum beta-lactamase (ESBL) producer defined in this study among E. coli, Klebsiella spp. and Proteus spp. were 45%, 48% and 17%, respectively. In the settings with high prevalence of the ESBL producer, flomoxef, which belongs to the oxacephem subgroup, and carbapenems retain their activity. The MIC₅₀ of flomoxef, meropenem and imipenem against total isolates were 1 μg/mL, ≤0.063 μg/mL and 0.25 μg/mL, respectively. Fifty-five carbapenem-resistant strains were isolated in this study. The carbapenem resistant rates of E. coli, Klebsiella spp. and Proteus spp. were 3%, 16% and 29%, respectively.

We conducted a postmarketing surveillance of tebipenem pivoxil granules (Orapenem® fine granules 10% for pediatric), an oral carbapenem antibacterial agent, between April 2010 and March 2013 to evaluate the safety and efficacy in patients with pneumonia or otitis media, or sinusitis.

Of 3,547 patients enrolled, 3,540 from whom survey forms were collected were analyzed. Of these 3,540 patients, there were a total of 3,331 patients included in the safety analysis, 2,844 in the efficacy analysis, 2,769 in the clinical efficacy analysis, and 461 in the bacteriological efficacy analysis.

The incidence of adverse drug reactions (ADRs) was 9.97% (332/3,331 patients), and the major ADRs were gastrointestinal disorders including diarrhoea in 317 patients (9.52%) Diarrhoea was reported in 313 patients (316 events), which were not clinically significant and 94.9% (297/313 patients) were recovery and/or remission.

The overall clinical efficacy rate was 94.0% (2,604/2,769 patients). The clinical efficacy rate by the type of infection was 95.6% (415/434 patients) for pneumonia, 93.7% (1,389/1,482 patients) for otitis media and 93.6% (659/704 patients) for sinusitis.

The eradication rate of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella (Branhamella) catarrhalis which are major causative organisms in pediatric infection of pneumonia, otitis media and sinusitis were 94.4% (134/142 strains), 92.2% (130/141 strains) and 97.8% (45/46 strains), respectively.

The compliance was good in 83.1% of the patients (2,767/3,331 patients).

Overall, Orapenem® fine granules 10% for pediatric showed good safety, efficacy, and compliance. These results indicate that Orapenem® fine granules 10% for pediatric is a useful agent in pediatrics with pneumonia or otitis media, or sinusitis.