The Japanese journal of antibiotics最新文献

Dissemination of carbapenem-resistant Enterobacteriaceae (CRE) poses a considerable threat to public health. Infections caused by CRE have limited treatment options and have been associated with high mortality rates. This resistance is largely the consequence of acquisition of carbapenemase genes. The genotypes in the geographical areas were initially different, as the Japanese epidemic was related to the IMP type (Class B), whereas the US epidemic was related to the KPC type (Class A). Thus, clinical detection of carbapenemase producers remains difficult based on each genotypes has specific screening method. CRE has many problems: some carbapenemase producers were susceptible to the carbapenems and some CRE were not producing carbapenemase which is associated with porin loss or efflux pomp. This review describes the current situation of CRE. It would facilitate accurate detection of CRE and approaches to prevention and treatment.

The balance of "Host-Pathogen-Antimicrobials" is crucial for the establishment of infectious diseases. Recently the ineffective cases, even though the appropriate antibiotics use, have been increasing since the several ineludible problems are rising, such as varied patient's background and the epidemic of the drug resistant pathogens, etc. Despite of the medical progression and the development of novel antimicrobials, the mortality of pneumonia has increased gradually and been the third cause of death in Japan. The conventional treatment depended on only bactericidal effect of antimicrobials faces a limit and the alternative strategies are required to overcome the current situation. This review addresses the potency of non-antibiotic antimicrobial agents as an alternative therapeutic strategy, especially focused on the activation of the innate host immunity induced by the macrolides and toll-like receptor agonist.

We herein discovered a highly resistant clinical isolate of Pseudomonas aeruginosa with MICs to amikacin, gentamicin, and arbekacin of 128 μg/mL or higher in a drug sensitivity survey of 92 strains isolated from the specimens of Yoka hospital patients between January 2009 and October 2010, and Achromobacter xylosoxidans was separated from this P. aeruginosa isolate. The sensitivity of this bacterium to 29 antibiotics was investigated. The MICs of this A. xylosoxidans strain to 9 aminoglycoside antibiotics were: amikacin, gentamicin, arbekacin, streptomycin, kanamycin, neomycin, and spectinomycin, 1,024 μg/mL or ≥ 1,024 μg/mL; netilmicin, 512 μg/mL; and tobramycin, 256 μg/mL. This strain was also resistant to dibekacin. This aminoglycoside antibiotic resistant phenotype is very rare, and we are the first report the emergence of A. xylosoxidans with this characteristic.

Antimicrobial susceptibility testing has been conducted continuously as postmarketing 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 Enterococcusfaecium, 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

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 beta-lactams. 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.

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 (ƒ · AUC/MIC ratio), against S. pneumoniae was 86.9-100%, but against E. coli was low (52.1-66.2%). The ƒ · 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.

To demonstrate clinical value of clavulanic acid/amoxicillin (CVA/AMPC) 1:14 combination dry syrup for acute bacterial rhinosinusitis (ABRS), the efficacy and safety were evaluated in a multicenter, open-label, uncontrolled study in 27 children with ABRS. The proportion of subjects who were 'cured' at the test of cure as the primary endpoint was 88.5%. In subjects with a major pathogenic bacteria at baseline (i.e., Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis) bacterial eradication was achieved in ≥ 80% of the subjects with the exception of β-lactamase non-producing ampicillin resistant H. influenzae: BLNAR and β-lactamase producing ampicillin resistant H. influenzae: BLPAR (β-lactamase producing amoxicillin/clavulanic acid resistant H. influenzae: BLPACR). The MIC of CVA/AMPC (1:14) was not higher than 4 μg/mL for all pathogens except one strain each of BLNAR and BLPAR (BLPACR). Drug-related adverse events were reported in 19% of patients (5/27 patients). All of the reported drug-related adverse events were classified as gastrointestinal disorders that have been commonly reported with antibacterial drugs. These results indicate that CVA/AMPC (1:14) was clinically useful for the treatment of ABRS and is also suggested that was effective especially for the treatment of ABRS in children caused by beta-lactamase-producing bacteria including M. catarrhalis.

Garenoxacin is a type of fluoroquinolone antibacterial agents. Previous studies have suggested that garenoxacin 400 mg once daily dose is appropriate for patients with normal to moderate renal disfunction against common bacteria of respiratory infections. However, limited information has been obtained in terms of treatment for severe renal failure patients, such as hemodialysis patients, with this drug. Twenty severe renal failure patients with respiratory infection received single garenoxacin dose (200 mg and 400 mg). By measuring blood concentration of garenoxacin, pharmacodynamics parameters, such as the peak plasma concentration (C(max)) and the area under the concentration curve (AUC), were calculated with NONMEM. After single dose of garenoxacin, C(max) at the 200 and 400 mg doses were within the range of 2.9 ± 0.6 and 6.0 ± 1.0 μg/mL, respectively. The corresponding values for AUC at the 200 and 400 mg doses were within the ranges of 62.3 ± 11.9 and 128.0 ± 12.5 μg x hr/mL, respectively. The mean half-life (T½) for garenoxacin appeared to be independent of dose (13.9 ± 2.2hr and 13.7 ± 1.9 hr at the 200 and 400 mg dose). There were no serious adverse events suspected to be related with garenoxacin. Consequently, for severe renal failure patients, the 400 mg once daily garenoxacin dose was expected to be effective against common bacteria of respiratory infections.

This is an integrated summary of the results obtained from a 3-decade multicenter study on bacteria isolated from surgical infections in Japan between July 1982 and March 2012. During the 3-decade study, 11,196 strains were isolated from 4,787 patients consisting of 2,132 patients with primary infection and 2,655 patients with surgical site infection. Almost half of the primary infection was peritonitis, which accounted for 42.3%-55.5%. In contrast, most of the surgical site infection was wound infection, which accounted for 49.3%-66.1%. The most commonly isolated bacteria throughout three decades were Escherichia coli (1,164 strains), Enterococcus faecalis (842), Staphylococcus aureus (833), Pseudomonas aeruginosa (706), Bacteroides fragilis (705), Klebsiella pneumoniae (498), Enterobacter cloacae (391) and coagulase-negative staphylococci (CNS) (325). Overall, S. aureus and CNS had sensitivity for vancomycin, whose MIC90s were 0.78 to 3.13 μg/mL; E. faecalis had sensitivity for vancomycin and imipenem, whose MIC90s were 0.78-4 μg/mL; E coli, E. cloacae, K. pneumoniae, and B. fragilis had preferable sensitivity for imipenem. No antibacterial agents had a long-term good activity (e.g. MIC90 < 2 μg/mL) for P aeruginosa and Bilophila wadsworthia. Among antibacterial agents tested, ciprofloxacin had most bactericidal activity for P. aeruginosa; its MIC90 varied from 0.5 to 8 μg/mL. The MIC90s of all antibacterial agents tested except levofloxacin and minocycline were at least 128 μg/mL for B. wadsworthia. S. aureus accounted for approximately 20% to 60% of bacteria isolated after clean operation. Overall, at least 55% of the bacteria isolated after clean operation consisted of S. aureus, CNS, E. faecalis, E. coli, E. cloacae, K. pneunoniae, P. aeruginosa, B. fragilis, and B. wadsworthia throughout three decades. However, the percentage of other Gram-positive and negative bacteria increased with the worse of sterile condition in surgical operation. E. faecalis tended to be most commonly isolated from patients having host-compromised factors including carcinoma, diabetes, anticancer agents, steroids, immunosuppressants, and radiation, while E. coli was commonly isolated from patients having no such factors. Two-drug-resistant P. aeruginosa was first isolated in 1987, thereafter was frequently isolated, and reached 69 strains for 30 years. Three-drug-resistant P. aeruginosa was isolated in 1990, 1996, and 1998 to reach 5 strains, but not isolated in remaining 13 years. Methicillin-resistant S. aureus was highly frequently isolated between 1988 and 1991. Subsequently, the isolation frequency declined, sometimes increased in 1998, 2005, and 2006, and thereafter maintained lower levels by 2011.