1 Women's and Children's Hospital, Adelaide, Australia; 2 Kitasato University School of Medicine, Kanagawa; 3 Nagasaki University School of Medicine, Nagasaki; 4 Teikyo University School of Medicine, Tokyo, Japan; 5 The JONES Group/JMI Laboratories, North Liberty, IA, USA
Keywords: in vitro activity , MDR , novel antimicrobial
Sir,
Peptide deformylase (PDF) has been recognized as a new target for antibacterial agents and several PDF inhibitors have been developed.1 LBM415 (NVP PDF-713) is a new PDF inhibitor with documented activities against Gram-positive organisms.25 The aim of this study was to evaluate the potency of LBM415 against key Gram-positive pathogens, as well as Haemophilus influenzae, from Japan where antimicrobial resistance levels are very high among clinically significant Gram-positive organisms and community-acquired respiratory pathogens.6,7
A total of 695 clinical isolates originally collected in Japan included Staphylococcus aureus (n=222), Haemophilus influenzae (n=119), Streptococcus pneumoniae (n=122), coagulase-negative staphylococci (CoNS; n=119), Enterococcus spp. (n=65) and Streptococcus spp. (n=48). No vancomycin-resistant enterococci were detected during this period. LBM415 (Novartis Pharmaceuticals, Basel, Switzerland) was diluted in broth microdilution trays or agar using NCCLS methods and media supplements as required.8 NCCLS quality control strains with established MIC ranges were included throughout the study.
The MIC distribution, MIC50 and MIC90 values are shown in Table 1. Oxacillin-resistant S. aureus had slightly lower LBM415 MIC values than oxacillin-susceptible strains. MIC50 and MIC90 values for LBM415 against oxacillin-resistant S. aureus were 2 log10 dilutions lower than those observed by Credito et al.,2
although they tested a smaller number of strains. CoNS had similar MIC results to S. aureus, although oxacillin-resistant strains appeared to be less susceptible than oxacillin-susceptible strains. All enterococci were inhibited at 8 mg/L of LBM415. All S. pneumoniae were inhibited at
2 mg/L of the PDF inhibitor, regardless of penicillin or multi-drug resistance (MDR). Similar results have been shown by Ednie et al.3
The LBM415 MIC90 for the ß-haemolytic streptococci was 0.5 mg/L; all streptococci were inhibited at
4 mg/L.
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The in vitro spectrum of LBM415 was similar to that of other recently published PDF inhibitor agents, such as BB-83698, BB-81384 and others with predominant Gram-positive activity.10,11 LBM415 has greater in vitro activity against H. influenzae.
This study indicates that LBM415 appears to be an active agent that may be suitable for the treatment of infections caused by Gram-positive organisms, including oxacillin-resistant staphylococci and MDR S. pneumoniae, but with lower activity against H. influenzae.
Acknowledgements
This study was supported by an educational/research grant from Novartis Pharmaceuticals, Inc.
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