The susceptibilities of clinical isolates to fluoroquinolones and other antimicrobial agents were surveyed to obtain an accurate understanding of trends in incidence and antimicrobial resistance. The ...samples were collected from across Japan, biennially or triennially, between 1994 and 2016 and a defined level of resistance to fluoroquinolone was determined.
Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae exhibited stable and high rates of susceptibility to fluoroquinolones over the period examined. For methicillin-resistant Staphylococcus aureus the rate of resistance to levofloxacin and ciprofloxacin was 81.3–93.5% and 83.2–94.2%, respectively, which was markedly higher than that of methicillin-susceptible S. aureus, while sitafloxacin-resistant methicillin-susceptible and methicillin-resistant S. aureus were isolated at 0.3–0.7% and 16.9–36.5%, respectively. The rate of levofloxacin or ciprofloxacin-resistant Escherichia coli increased from around 2–3% between 1994 and 1998 to around 35% in 2016, but the rate of fluoroquinolone-susceptible Klebsiella pneumoniae stayed high at over 94.6% during the study period. Although no fluoroquinolone-resistance in clinical isolates of Salmonella spp. was detected from 1994 to 2002, the resistance rate increased slightly after 2004 and reached to 1.9%–4.7% in 2016. The rate of fluoroquinolone-susceptible Pseudomonas aeruginosa isolated from urinary tract and respiratory tract infections improved during the period examined from 41.8–67.0% to 91.2–94.2%, and from 78.9-88.5% to 90.1–94.6%, respectively. Against Acinetobacter spp., the susceptibility rate of fluoroquinolones was almost constant at around 90%, but one multidrug-resistant isolate was detected in 2013. Overall, the susceptibility to fluoroquinolones was maintained over 20 years against tested bacteria except for MRSA and E. coli.
Interleukin (IL)-17 is a key member of the Th17 cytokines and has been reported to be involved in the pathomechanisms underlying various diseases, including infectious diseases. Infections with ...community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) have garnered worldwide attention, and the representative USA300 strain is known to cause pneumonia in healthy people, which can be lethal. However, little is known about the role of IL-17 in CA-MRSA pneumonia. In this study, we investigated the role of IL-17 in a CA-MRSA pneumonia animal model. Mortality was higher and occurred at an earlier stage of infection in the IL-17A-knockout mice than in the wild-type (P < 0.01) and IL-17A/F-knockout mice (P < 0.05); however, no significant difference in the intrapulmonary bacterial counts was observed among the three groups of mice. Moreover, the IL-17A-knockout group showed significantly higher levels of IL-17F and granulocyte-colony stimulating factor (G-CSF) and a significantly higher neutrophil count in the bronchoalveolar lavage fluid than the other groups. These results confirmed that G-CSF expression significantly increased, and significant neutrophilic inflammation occurred under conditions of IL-17A deficiency in the murine CA-MRSA pneumonia model.
Abstract Macrolides have been reported to exert a variety of effects on both host immunomodulation and repression of bacterial pathogenicity. In this study, we report that the 3′,5′-cyclic diguanylic ...acid (c-di-GMP) signaling system, which regulates virulence in Pseudomonas aeruginosa , is affected by the macrolide azithromycin. Using DNA microarray analysis, we selected a gene encoding PA2567 related to c-di-GMP metabolism that was significantly affected by azithromycin treatment. Expression of the PA2567 gene was significantly repressed by azithromycin in a time- and dose-dependent manner, whereas no difference in PA2567 gene expression was observed in the absence of azithromycin. In-frame deletion of the PA2567 gene affected both virulence factors and the quorum-sensing system, and significantly decreased total bacteria in a mouse pneumonia model compared to the wild-type strain ( P < 0.05). These results suggest that macrolides possess the ability to modulate c-di-GMP intracellular signaling in P. aeruginosa.
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