University of Iowa College of Medicine, Iowa City; the JONES Group/JMI Laboratories, North Liberty, IA; and Tufts University School of Medicine, Boston, MA, USA
Received 27 July 2001; returned 7 January 2002; revised 6 February 2002; accepted 13 February 2002.
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Abstract |
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Introduction |
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The purpose of this study was to determine the in vitro activity of BMS284756 against bacterial bloodstream infection (BSI) isolates from the SENTRY antimicrobial surveillance programme. The potency and spectrum of BMS284756 were compared with that of other quinolones, including ciprofloxacin, gatifloxacin and levofloxacin.
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Materials and methods |
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A total of >10 000 bacterial BSI isolates were obtained from participant laboratories in North America (31 sites), Latin America (10 sites) and Europe (17 sites) from January to December 2000, as part of the SENTRY programme. The top 12 occurring pathogens accounted for 10 654 isolate epi-sodes during this time period and were as follows: S. aureus (3094 isolates), Escherichia coli (1866), coagulase-negative staphylococci (CoNS; 1461), Enterococcus spp. (1045) Klebsiella spp. (884), Pseudomonas aeruginosa (556), S. pneumoniae (482), Enterobacter spp. (437), b-haemolytic streptococci (303), Acinetobacter spp. (210), viridans group streptococci (164) and Serratia spp. (152). This rank order was very similar to the rank order in previous SENTRY programme years since 1997, with Serratia spp. replacing Proteus mirabilis in the top 12 pathogens for the 2000 SENTRY pro-gramme in the United States (US) and Canada.7 Likewise, the rank order of pathogens from Latin America was similar to previous years.8
Study design and susceptibility methods
The study protocol dictated that each medical centre collect the first 20 consecutive clinically significant BSI isolates (one per patient episode) per month and forward them to the reference laboratory (University of Iowa and JMI Laboratories, IA, USA) for susceptibility testing. Isolates were identified using the Vitek System (bioMérieux Inc., Hazelwood, MO, USA) supplemented with conventional tests as needed. Stock cultures of all isolates were kept at 80°C. All isolates were susceptibility tested, utilizing NCCLS reference broth microdilution methods, against a panel of antimicrobial agents, including BMS284756, ciprofloxacin, levofloxacin and gatifloxacin.9,10 A colony suspension equal to a 0.5 McFarland standard was made for all organisms and a volume of 50 µL (100 µL for S. pneumoniae) of this suspension was pipetted into 10 mL of cation-adjusted MuellerHinton broth or MuellerHinton broth supplemented with lysed horse blood for the Streptococcus spp. Using an autoinoculator, 100 µL of the inoculum suspension were dispensed into the wells of a dry form panel (TREK Diagnostics, Westlake, OH, USA). Colony counts were carried out regularly to ensure a starting inoculum of c. 35 x 105 cfu/mL. The panels were incubated in an ambient air environment at 35°C for 1620 h for all Gram-negative organisms and 2024 h for all Gram-positive and fastidious organisms. Trays were then read manually and an endpoint of no organism growth was established as the MIC per NCCLS standards.9,10 Quality control was carried out using the following strains recommended by NCCLS: S. aureus ATCC 29213, E. faecalis ATCC 29212, S. pneumoniae ATCC 49619, Haemophilus influenzae ATCC 49766 and 49247, E. coli ATCC 25922 and 35218, and P. aeruginosa ATCC 27853.
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Results |
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Although the fluoroquinolones tested were very active against the viridans group streptococci (98100% susceptible) and ß-haemolytic streptococci (99100%), BMS284756 was at least four-fold more potent than the other quinolones (MIC90 0.12 versus 0.51 mg/L). Against S. pneumoniae, BMS284756 (MIC90 0.06 mg/L) was eight-fold more potent than gatifloxacin (MIC90 0.5 mg/L), 16-fold more potent than levofloxacin (MIC90 1 mg/L) and 32-fold more potent than ciprofloxacin (MIC90 2 mg/L). However, as seen with the other Streptococcus spp., levofloxacin (>99% of pneumococcal isolates susceptible), gatifloxacin (>99% susceptible) and BMS284756 (100% susceptible) were all very active against S. pneumoniae at their respective NCCLS breakpoint concentrations.911
BMS284756 was generally two- to four-fold less potent than the other quinolones against Enterobacteriaceae, with MIC90s ranging from 0.5 mg/L (E. coli) to >4 mg/L (Serratia spp.), compared with 0.252 mg/L of the other three agents (Table 2). At the proposed or recommended NCCLS breakpoints, BMS284756 was comparable to the other agents against E. coli (92% susceptible versus 9192%), Enterobacter spp. (91% versus 9092%) and Klebsiella spp. (95% versus 9395%), but was less active against Serratia spp. (88% versus 9297%).
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Discussion |
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Footnotes |
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References |
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Fung-Tomc, J. C., Minassian, B., Kolek, B., Huczko, E., Aleksunes, L., Stickle, T. et al. (2000). Antibacterial spectrum of a novel des-fluoro (6) quinolone, BMS-284756. Antimicrobial Agents and Chemotherapy 44, 33516.
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Pfaller, M. A., Jones, R. N., Doern, G. V., Kugler, K. C. & the SENTRY Participants Group. (1998). Bacterial pathogens isolated from patients with blood stream infections: frequencies of occurrence and antimicrobial susceptibility patterns from the SENTRY Antimicrobial Surveillance Program (United States and Canada, 1997). Antimicrobial Agents and Chemotherapy 42, 176270.
8 . Sader, H. S., Pfaller, M. A., Jones, R. N., Doern, G. V., Gales, A. C., Winokur, P. L. et al. (1999). Bacterial pathogens isolated from patients with blood stream infections in Latin America, 1997: frequencies of occurrence and antimicrobial susceptibility patterns from the SENTRY Antimicrobial Surveillance Program. The Brazilian Journal of Infectious Diseases 3, 97110.[Medline]
9 . National Committee for Clinical Laboratory Standards. (2000). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that Grow AerobicallyFifth Edition: Approved Standard M7-A5. NCCLS, Wayne, PA.
10 . National Committee for Clinical Laboratory Standards. (2001). MIC Testing: Supplemental Tables M100-S10 (M7). NCCLS, Wayne, PA.
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Fung-Tomc, J., Minassian, B., Kolek, B., Washo, T., Huczko, E., & Bonner, D. (2000). In vitro antibacterial spectrum of a new broad-spectrum 8-methoxy fluoroquinolone, gatifloxacin. Journal of Antimicrobial Chemotherapy 45, 43746.