Susceptibility to amoxycillin-clavulanate among clinical isolates of Escherichia coli resistant to cefoxitin.
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Amoxicillin-Potassium Clavulanate Combination↗
Biomedical subjects
D J Biedenbach
Publications and source records attributed to D J Biedenbach.
Comparisons of the in vitro susceptibility testing results for garenoxacin using six different national methods: report from the garenoxacin international bridging study.
BACKGROUND: Laboratories worldwide carry out MIC/disc diffusion (DD) tests using various national methods, often published by local organizations. Potentially different results may complicate drug development or registration between the US methods and those used in the European Union (EU). This study uses a new des-F(6)quinolone, garenoxacin, to compare in vitro results among the most utilized antimicrobial susceptibility testing methods. METHODS: Investigators in France, Germany, Spain, Sweden and the UK tested two bacterial collections designated, challenge (CC; n = 330) containing quinolone-resistant strains and national (NC; n = 540) that were recent clinical isolates (2000-2001). Results were compared with values derived from the National Committee for Clinical Laboratory Standards (NCCLS) methods, carried out by the US coordinating site. Discords (greater than four-fold) between MIC method results were repeated. Results were analysed for variation from the NCCLS results (+/-1-2 dilutions or greater than 3-6 mm) and by regression statistics. Ciprofloxacin was used as the control quinolone agent. RESULTS: CC and NC testing compliance averaged 98.4% and 86.4% among participating centres, respectively, and correlation (r) of the national method to the NCCLS MIC was: France (0.98), Germany (0.95), Spain (0.98), Sweden (0.96) and UK (0.95). CC produced MIC results that were identical to the NCCLS (Spain) to 0.6 x log(2) greater (Germany), but the percentage of strains +/-2 dilutions versus NCCLS MIC results was 98% (Germany)-100% (Sweden, UK). Similar patterns were observed for the NC (r = 0.93-0.98), and all nations had >99% of results within +/-2 dilutions (+/-6 mm for disc tests) of NCCLS values. MIC results from four national methods were slightly elevated compared to the NCCLS result (average 0.2 x log(2)). Control ciprofloxacin MIC and DD test results showed similar patterns. CONCLUSIONS: Inter-method garenoxacin susceptibility test results indicate that MIC and zone diameter endpoints derived from five EU methods compare favourably to the NCCLS method results, and generally were identical or a fraction of a log(2) dilution step higher. In contrast, zone diameters for garenoxacin and ciprofloxacin were routinely larger for the EU methods. This unique inter-method 'bridging' experiment allows regulatory agencies to better correlate in vitro testing results derived from procedures that use different national methodologies.
Anti-Bacterial Agents↗
Re-evaluation of quality control guidelines for gatifloxacin and garenoxacin (BMS284756) when susceptibility testing Haemophilus influenzae and Streptococcus pneumoniae.
An eight laboratory M23-A2 quality control (QC) study was performed for the re-evaluation of gatifloxacin, a new fluoroquinolone, using disk diffusion tests against Streptococcus pneumoniae ATCC 49619. The study also re-evaluated garenoxacin, a novel investigational des-F(6)-quinolone, using disk diffusion tests against S. pneumoniae ATCC 49619 and broth MIC for Hemophilus influenzae ATCC 49247. The gatifloxacin zone diameter results for S. pneumoniae did not indicate a need for QC range modification (26-34 mm; 98.3% of results); however, the garenoxacin zone diameters did demonstrate a need for a minor modification (1 mm; 26-34 mm; 96.3% of reported results). The broth MIC results for H. influenzae showed that 83.1% of the results were at the upper limit of the current range (0.008 microg/ml) published by the National Committee for Clinical Laboratory Standards (NCCLS). The proposed correction could either be 0.002-0.015 microg/mlor 0.004-0.015 microg/ml, each encompassing 100.0% of reported results (prior and current studies). All MIC results for control drugs, levofloxacin and moxifloxacin (disks) or gatifloxacin and clarithromycin (MIC), were within published NCCLS ranges.
Anti-Infective Agents↗
Susceptibility trends of haemophilus influenzae and Moraxella catarrhalis against orally administered antimicrobial agents: five-year report from the SENTRY Antimicrobial Surveillance Program.
The assessment of orally administered antimicrobial susceptibilities of common pathogens that cause community-acquired respiratory tract infections (CARTI) has become exceedingly important due to the number of office visits for this indication. Numerous local, regional and global studies have documented the susceptibilities of Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis, the most common CARTI pathogens. SENTRY Antimicrobial Surveillance Program sites in North and Latin America, and Europe were requested to send a combined total of 100 isolates of these pathogens to the local monitor for reference broth microdilution testing (1997-2001). This study compared the susceptibility profiles of H. influenzae and M. catarrhalis isolates (13,370 strains) from the three geographic regions over a five year period. beta-lactamase mediated ampicillin resistance among H. influenzae was highest among North American isolates (27.9%) compared to Latin America and Europe (16.2 to 16.3%), although it was noted that during the five year study period, ampicillin resistance was steadily increasing in the latter two regions. Cefprozil (84.3% susceptible) and clarithromycin (81.1% susceptible) were also less active against North American H. influenzae isolates. Latin American isolates were much less susceptible to trimethoprim/sulfamethoxazole (T/S; 59.3%) compared to the other regions (75.8 to 78.6%). M. catarrhalis isolates were also significantly less susceptible to T/S in Latin America (10.5% resistance). The production of beta-lactamase enzymes among the M. catarrhalis isolates exceeded >95% in all three regions during the five year period. The fluoroquinolones (FQ) remained very active against these two respiratory pathogens with rare isolates with elevated FQ MIC results. It is apparent from this investigation that many commonly prescribed empiric treatments remain viable therapeutic options for CARTI caused by these two Gram-negative respiratory tract pathogens.
Administration, Oral↗
Validation of commercial dry-form broth microdilution panels for susceptibility testing of AZD2563, a new long-acting oxazolidinone.
The MIC results using a dry-form broth microdilution panel (TREK Diagnostic/Sensititre, Westlake, OH, USA) were validated for AZD2563, a novel oxazolidinone compound. In comparision studies against reference frozen-form panels, the commercial MIC results were the same as the reference calue for 82.7% of organisms and all results were within +/- one log2 dilution. Using 462 organisms, most from three genus groups (enterococci, staphylococci, streptococci), test results indicate that Sensititre MIC values were comparable to the reference test and can be utilized in clinical trials of for routine laboratory use when testing AZD2563 and linezolid, the drug class comparator.
Anti-Bacterial Agents↗
Revision of linezolid disk diffusion quality control guidelines for testing Staphylococcus aureus ATCC 25923: an independent seven-laboratory trial.
The accuracy of the published disk diffusion quality control (QC) range for linezolid for Staphylococcus aureus ATCC 25923 has been reported to be problematic, prompting a multicenter study to determine if revision was necessary. Five out of seven laboratories reported values outside the current QC range. Three participants had significant (13.3-60.0%) 'unacceptable' results with zones smaller than the established range. Overall, a range of 21-32 mm was shown (82.4% within the NCCLS published range). A revision (25-31 mm; 95.7% of results) of the QC range is necessary when testing S. aureus ATCC 25923 against linezolid.
Acetamides↗
Comparative antimicrobial spectrum and activity of the desfluoroquinolone BMS284756 (T-3811) tested against non-fermentative Gram-negative bacilli.
OBJECTIVE: To compare the in vitro activity of BMS284756, a desfluoroquinolone, with four fluoroquinolones against 129 Pseudomonas aeruginosa strains, 97 Stenotrophomonas/Burkholderia group strains and 43 Acinetobacter spp. strains by three in vitro test methods. METHODS: The activity of BMS284756 was determined using the NCCLS reference broth microdilution method and E test (AB Biodisk, Solna, Sweden). These methods were compared for test accuracy, and 5-microg disk zone diameters were compared for interpretative accuracy using the susceptible breakpoint of < or =4 mg/L recommended by the manufacturer. All strains tested were derived from the 1999-2000 SENTRY Antimicrobial Surveillance Program organism collection. RESULTS: Comparative quinolone potency against P. aeruginosa was as follows: ciprofloxacin (MIC50, 0.25 mg/L) > gemifloxacin (MIC50, 0.5 mg/L) > levofloxacin = gatifloxacin (MIC50, 1 mg/L) > BMS284756 (MIC50, 4 mg/L). The MIC50 value for BMS284756 versus Stenotrophomonas/Burkholderia group was 2 mg/L. This potency was similar to that of other quinolones reported previously. The MIC50 results for the Acinetobacter spp. were ciprofloxacin at >2 mg/L, levofloxacin, gatifloxacin and gemifloxacin at 4 mg/L, and BMS284756 at >4 mg/L, all intermediate or resistant concentrations. The E test results compared favorably with the reference dilution test results for P. aeruginosa, Stenotrophomonas/Burkholderia group, and Acinetobacter spp., with an overall essential agreement of 97.0% +/- 2 log2 dilution steps. E test MIC results tended to be slightly lower when testing Stenotrophomonas/Burkholderia group strains. The disk diffusion method correlated well for P. aeruginosa (r = 0.94), Stenotrophomonas/Burkholderia group (r = 0.84) and Acinetobacter spp. (r = 0.99) strains. CONCLUSIONS: BMS284756 was generally less active than other comparison quinolones when tested against non-fermentative Gram-negative bacilli. Its spectrum remains equivalent only if dosing schedules substantiate a proposed susceptible breakpoint of < or =4 mg/L.
Anti-Infective Agents↗
Multicentre assessment of linezolid antimicrobial activity and spectrum in Europe: report from the Zyvox antimicrobial potency study (ZAPS-Europe).
OBJECTIVE: To evaluate the in vitro spectrum and activity of linezolid, a recent oxazolidinone, according to well-controlled surveillance data from 42 medical centers in 13 countries throughout Europe. METHODS: Participants tested the susceptibility of 125 clinical strains of enterococcal and staphylococcal species against 13 drugs using reference broth microdilution trays or the standardized disk diffusion method of the National Committee for Clinical Laboratory Standards (NCCLS). Streptococcal species (n = 25 at each center) were tested against six drugs using E test (AB BIODISK, Solna, Sweden). Quality assurance testing was conducted using NCCLS-recommended strains and verification of resistance to linezolid and other selected agents was performed by retesting strains at the regional (Europe) and international (USA) monitor sites. RESULTS: A total of 5598 strains from throughout Europe (91% compliance) were tested. Vancomycin resistance was reported in only 0.6 and 3.0% of Enterococcus faecalis and E. faecium, respectively. Penicillin resistance occurred in 25.1% of Streptococcus pneumoniae; 4.9% at the high-level (> or =2 mg/L). The MIC90 for linezolid was 1 mg/L for streptococci and 2 mg/L for enterococci and staphylococci. Using the US FDA- and EUCAST-recommended susceptible breakpoints for linezolid, there were no confirmed reports of linezolid resistance [minimum inhibitory concentration (MIC), > or =8 mg/L]. The distribution of linezolid MIC values was unimodal and varied between 0.25 and 1 mg/L for streptococci (>90% of isolates), and between 1 and 2 mg/L for staphylococci (>90%) and enterococci (>95%). There were no differences in linezolid susceptibility in the vancomycin-, oxacillin-, or penicillin-resistant subsets of strains when compared to susceptible organism populations. CONCLUSIONS: Compared to the North American component of this study, there was substantially less vancomycin resistance among E. faecium isolates (Europe 3.0% vs. North America 63.4%). While the occurrence of penicillin-resistant S. pneumoniae in Europe and North America was similar (25.1% vs. 29.7%), the recovery of high-level penicillin-resistant strains was nearly three-fold higher in North America (4.9% vs. 13.2%). Only linezolid was universally active against all the tested Gram-positive isolates at </=4 mg/L.
Acetamides↗
Molecular epidemiology of extended-spectrum beta-lactamase-producing, fluoroquinolone-resistant isolates of Klebsiella pneumoniae in Taiwan.
Strains of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) have emerged worldwide. Concomitant ciprofloxacin resistance with ESBL production in K. pneumoniae isolates would severely restrict treatment options. Among 39 (18.5%) of 211 ESBL-KP isolates resistant to ciprofloxacin (MIC, >/=4 micro g/ml), 37 (95%) were high level resistant (MIC, >/=16 micro g/ml). These isolates were also cross resistant to the newer fluoroquinolones, including levofloxacin, gatifloxacin, gemifloxacin, and garenoxacin (BMS 284756). Sitafloxacin was most active against these ciprofloxacin-resistant ESBL-KP isolates with MICs for 67% of the isolates being </=2 micro g/ml. The molecular epidemiology of these multiresistant isolates was investigated by automated ribotyping and pulsed-field gel electrophoresis (PFGE). Ribotyping identified 18 different strains among the 39 ciprofloxacin-resistant ESBL-KP isolates. The majority (67%) of these isolates were contained in six ribogroups which were further confirmed by PFGE. The distribution of the six major strains of ciprofloxacin-resistant ESBL-KP within Taiwan included one (ribogroup 255.3-PFGE type E) with a nationwide distribution and several institution-specific strains. Interhospital cooperation appears necessary, with strict infection control practices coupled with restriction of fluoroquinolone and extended-spectrum beta-lactam use to control both the major epidemic strain and the more diverse strains observed within individual institutions.
Anti-Infective Agents↗
In vitro activity of linezolid (U-100766) against Haemophilus influenzae measured by three different susceptibility testing methods.
Linezolid has excellent antibacterial activity against a wide range of Gram-positive organisms. Early in vitro investigations suggested that the compound also had activity against some Gram-negative species, including those commonly associated with community-acquired respiratory tract infections (Haemophilus influenzae and Moraxella catarrhalis). Against 603 recent clinical isolates of H. influenzae from geographically diverse regions of the world, tested by the reference broth microdilution method (HTM), linezolid MIC values ranged from 2-64 microg/ml (MIC50 and MIC90 at 16 microg/ml and 32 microg/ml, respectively). A subset of 328 strains was also tested to compare broth microdilution and Etest (AB BIODISK, Solna, Sweden) methodologies. The Etest method produced slightly higher MIC results attributable to a growth-enhancing effect of the 5% CO2 incubation used in the test procedure and pH changes. Linezolid activity versus H. influenzae was limited as evidenced by reference test results (susceptible breakpoints at < or = 2 or < or = 4 microg/ml) and variable endpoints were obtained when alternative methods were used such as the Etest or standardized disk diffusion procedures. Clinical laboratories should limit the testing of linezolid against Gram-negative species (H. influenzae).
Acetamides↗
Carbapenem-resistant Serratia marcescens isolates producing Bush group 2f beta-lactamase (SME-1) in the United States: results from the MYSTIC Programme.
Two carbapenem (imipenem, meropenem)-resistant Serratia marcescens strains were isolated in the United States (Chicago, IL) through the 1999 MYSTIC (Meropenem Yearly Susceptibility Test Information Collection) Programme. The S. marcescens antimicrobial susceptible patterns were: susceptible to ceftriaxone, ceftazidime, and cefepime (MICs, < or = 0.25 microg/ml), and resistance to the carbapenems (imipenem and meropenem; MIC, > 32 microg/ml) and aztreonam (MIC, > = 16 microg/ml). Each S. marcescens isolate shared an identical epidemiologic type (ribotype and PFGE) and the outer membrane protein profile was also identical to those of the wild type susceptible strains from the same medical center. The PCR utilizing bla(sme-1) primers amplified a gene product that was identified as consistent with SME-1 after DNA sequencing. Imipenem and meropenem resistance due to production of carbapenem-hydrolyzing enzymes among clinical isolates is still very rare, but microbiology laboratories should be aware of these chromosomally encoded enzymes among class C beta-lactamases producing enteric bacilli such as S. marcescens and Enterobacter cloacae.
Drug Resistance, Microbial↗
Activity of BMS284756 against 2,681 recent clinical isolates of Haemophilus influenzae and Moraxella catarrhalis: Report from The SENTRY Antimicrobial Surveillance Program (2000) in Europe, Canada and the United States.
Although the isolation and detection of fluoroquinolone-resistant Haemophilus influenzae and Moraxella catarrhalis has been a very rare occurrence, newer agents in the quinolone class must be evaluated to determine their comparative potencies and to develop in vitro testing methods. BMS284756 is an investigational desfluoro(6)-quinolone with a spectrum of activity most similar to recently introduced agents such as gatifloxacin and trovafloxacin. This compound was compared to levofloxacin, gatifloxacin, ciprofloxacin and moxifloxacin, as well as other orally administered antimicrobials against 1,872 H. influenzae and 810 M. catarrhalis isolates. Two Canadian H. influenzae strains had ciprofloxacin MICs elevated above the normal wild type susceptible MIC population (> 0.06 microg/mL). All other strains of H. influenzae and M catarrhalis were highly susceptible to the tested quinolones (MIC(90,) < or = 0.016 or 0.03 microg/mL). For the two H. influenzae isolates with elevated quinolone MICs the potency rank order was: gatifloxacin and BMS284756 (MICs, 0.25 and 1 microg/mL) > levofloxacin and moxifloxacin > ciprofloxacin (MICs, 0.5 and > 2 microg/mL). The comparison of Etest (AB BIODISK, Solna, Sweden) and disk diffusion results to the reference broth microdilution values produced acceptable intermethod accuracy when applied to BMS284756. This novel desfluoro compound possesses promising activity against fastidious Gram-negative respiratory tract pathogens and further clinical development is underway.
Anti-Infective Agents↗
In vitro antimicrobial activity of GAR-936 tested against antibiotic-resistant gram-positive blood stream infection isolates and strains producing extended-spectrum beta-lactamases.
GAR-936, a new, semisynthetic glycylcycline, has shown good antibacterial activity against a wide range of clinically important Gram-positive and -negative aerobic bacteria including Streptococcus pneumoniae, Hemophilus influenzae, Moraxella catarrhalis, Neisseria gonorrhoeae, most Enterobacteriaceae, Staphylococcus aureus and Enterococcus spp. The purpose of this study was to determine the activity of GAR-936 against a range of Gram-positive and -negative bloodstream isolates including many strains producing extended-spectrum beta-lactamases (ESBLs). Six hundred four bloodstream isolates of Gram-positive cocci collected as part of the SENTRY surveillance program were selected for their geographic diversity. GAR-936 was also tested against an additional 176 Gram-negative cocci isolates (Klebsiella pneumoniae, 98 strains; Escherichia coli, 78 strains), 96 of which were ESBL-producers. Broth microdilution testing was used to determine the susceptibility of the selected organisms and a range of comparator antimicrobial agents whose choice was based on their activities against the selected pathogens and included a mix of both newer and older agents. Presence of an ESBL-producing strain was confirmed using the clavulanate test. GAR-936 demonstrated impressive activity against all 604 strains of Gram-positive cocci, with an MIC range of <or=0.015-1 microg/mL, and MIC(90)s ranging from <or=0.05 microg/mL for S. pneumoniae to 0.25 for S. aureus and coagulase-negative staphylococci. MICs against the 176 Gram-negative isolates were higher (range 0.06-4 microg/mL), with MIC(90)s of 0.25-1 microg/mL. The activity of GAR-936 was relatively unaffected by the presence of ESBLs. The activity of GAR-936 was particularly impressive against Gram-positive cocci when compared against the test results for vancomycin and the newer antimicrobial agents, linezolid and quinupristin/dalfopristin. The MIC(90)s for GAR-936 were significantly lower than the comparator agents for all species tested with particularly impressive results against S. pneumoniae and enterococci.
Anti-Bacterial Agents↗
Assessment of BMS284756 MIC and 5-microg disk diffusion quality control studies tested against seven American type culture collection strains.
BMS284756 is a novel des-fluoro(6)-quinolone with antimicrobial activity similar to recently developed fluorinated quinolones. The purpose of this investigation was to determine the appropriate disk diffusion and MIC quality control (QC) ranges for BMS284756 when used against commonly tested QC strains (M23-A2). The BMS284756 5-microg disk content was tested against Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Hemophilus influenzae ATCC 49247, Streptococcus pneumoniae ATCC 49619 and Staphylococcus aureus ATCC 25923. In addition, Enterococcus faecalis ATCC 29212 and S. aureus ATCC 29213 were evaluated by the broth microdilution method. Seven laboratories tested 2 disk lots on 3 agar media or 3-4 broth lots over a 10 day period. A total of 420 zone diameter values and 210 or 280 MIC values per organism were generated. The following disk diffusion and MIC QC ranges were suggested for BMS284756 and the seven QC strains: E. coli ATCC 25922 (28-35 mm/0.004-0.016 microg/mL), E. faecalis ATCC 29212 (0.03-0.25 microg/mL), S. aureus ATCC 25923 (30-36 mm), S. aureus ATCC 29213 (0.004-0.016 microg/mL), P. aeruginosa ATCC 27853 (19-25 mm/0.5-2 microg/mL), H. influenzae ATCC 49247 (33-41 mm/0.002-0.008 microg/mL), S. pneumoniae ATCC (26-33 mm/0.016-0.06 microg/mL). The proportion of participant results observed within the proposed ranges was 97.4-98.8% and 94.6-100% for the disk diffusion and MIC tests, respectively.
Anti-Infective Agents↗
Antimicrobial resistance trends in medical centers using carbapenems: report of 1999 and 2000 results from the MYSTIC program (USA).
Trends in susceptibility to antimicrobials were assessed from United States participants using 4488 isolates in the MYSTIC Program, 1999 (10 centers) through 2000 (15 centers). Diverse types of hospitals (general service, university, cancer, federal, pediatric, cystic fibrosis) were enrolled from 13 states. In 2000, oxacillin-susceptible staphylococci were 100% susceptible to meropenem, imipenem, and cefepime; but only 88% of strains were susceptible to ceftazidime. Among Enterobacteriaceae, > or = 96% of Enterobacter spp., Citrobacter spp., and Serratia spp. were susceptible to meropenem, imipenem, and cefepime; but ceftazidime, ceftriaxone, and piperacillin/tazobactam had 5-20% resistance rates. Extended-spectrum beta-lactamase resistance rates in Klebsiella spp. and Escherichia coli (6-7% and 3-5%, respectively) were stable over 2 years. Acinetobacter spp. were 78-81% susceptible to carbapenems but only 63-72% susceptible to ciprofloxacin. Meropenem, tobramycin, and piperacillin/tazobactam were the most active against Pseudomonas aeruginosa, but ciprofloxacin inhibited only 74% in 2000. Overall, meropenem remained the most potent agent, especially against ceftazidime- or piperacillin/tazobactam-resistant strains.
Academic Medical Centers↗
Comparative antimicrobial activity of ABT-773, a novel ketolide, tested against drug-resistant Gram-positive cocci and Haemophilus influenzae.
The antimicrobial activity of ABT-773, a novel ketolide, was tested against 618 Gram-positive strains collected from various surveillance programmes between 1997 and 2000. ABT-773 has potent activity against Streptococcus pneumoniae (MIC90, < or = 0.03-0.12 mg/l), beta-haemolytic streptococci (MIC90, < or = 0.03 mg/l) and viridans group streptococci (MIC90, < or = 0.03 mg/l), including erythromycin-resistant strains. In contrast, ABT-773 was less active against erythromycin-resistant Staphylococcus aureus (31% susceptible at < or = 0.25 mg/l), coagulase-negative staphylococci (41% susceptible) and enterococci (30% susceptible). Haemophilus influenzae (MIC90, 4 mg/l) was less inhibited by the two ketolides tested, and ABT-773 was generally two- to fourfold more potent than telithromycin. The ketolides appear to have potential clinical use against some Gram-positive species resistant to macrolides.
Anti-Bacterial Agents↗
Comparative antimicrobial spectrum and activity of BMS284756 (T-3811, a desfluoroquinolone) tested against 656 Enterobacteriaceae, including preliminary in vitro susceptibility test comparisons and development.
BMS284756 (T-3811), a novel des-F(6)-quinolone, was evaluated using isolates of Enterobacteriaceae from the SENTRY Antimicrobial Surveillance Program tested by Etest (AB BIODISK, Solna, Sweden), reference broth microdilution and disk diffusion (5-microg) methods. Ciprofloxacin, levofloxacin, gemifloxacin and gatifloxacin were also tested by broth microdilution as comparator antimicrobial agents within the same drug class. The 656 isolate collection included species from the genera Citrobacter, Enterobacter, Escherichia, Hafnia, Klebsiella, Morganella, Pantoea, Proteus, Providencia, Salmonella, and Serratia. BMS284756 was slightly less active than comparison fluoroquinolones against these isolates (MIC(90), 4 mg/l versus 0.06-2 mg/l). However, at a proposed susceptible breakpoint of < or =4 mg/l, 90.7% of the isolates processed were susceptible to BMS284756, demonstrating an equivalent spectrum of activity to all other agents except gemifloxacin (86.6%). In general, isolates requiring >4 mg/l of BMS284756 for inhibition of growth were also less susceptible to the comparators suggesting cross-resistance is common between des-F(6)- and fluoro-quinolones. Excellent correlation was observed between broth microdilution MIC results and 5-microg disk zone diameters (r=0.94), and between broth microdilution dilution and Etest MIC values (r=0.96). In conclusion, BMS284756 has an activity and spectrum similar to contemporary fluoroquinolones and in vitro test methods (NCCLS, Etest) appear accurate and reproducible
Anti-Infective Agents↗
Antimicrobial activity of BMS 284756 (T-3811) against Neisseria gonorrhoeae tested by three methods.
The potency of BMS 284756, a novel des-F(6)-quinolone, was tested against 137 clinical isolates of Neisseria gonorrhoeae including 50 strains observed to be resistant to ciprofloxacin and other newer quinolones. The gonococci were tested using NCCLS methods (agar dilution, disk diffusion) and Etest. BMS 284756 potency versus N. gonorrhoeae was generally two- to four-fold greater than ciprofloxacin. Penicillin resistance in the absence of ciprofloxacin resistance did not affect BMS 284756 activity. However, elevated ciprofloxacin MICs were associated with higher BMS 284756 MIC results as follows (BMS 284756 MIC(50)/MIC range in mg/l): ciprofloxacin-susceptible strains (0.016 or 0.03/0.004-0.06), ciprofloxacin-intermediate strains (0.06 or 0.12/0.008-0.25) and ciprofloxacin-resistant strains (0.12 or 0.5/0.12-1). Etest MICs were routinely lower than those produced by the reference agar dilution method, but the correlation coefficient remained acceptable (r = 0.87). Similarly acceptable correlation was achieved with 5 microg disk zone diameters (r = 0.78), where all zones were > or = 28 mm (MIC < or = 1 mg/l). In conclusion, BMS 284756 was very active against N. gonorrhoeae (MIC(50) 0.03 mg/l overall) including ciprofloxacin-resistant strains and could be considered as a single-dose therapeutic option for gonorrhoea.
Anti-Infective Agents↗