In vitro activity of linezolid and 11 other antimicrobials against 566 clinical isolates and comparison between NCCLS microdilution and Etest methods

The in vitro activity of linezolid and 11 other antimicrobials was determined for 566 clinical isolates of Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus spp., Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, some of them resistant to several antibiotics, using a broth microdilution method and the Etest method. All Gram-positive organisms tested were inhibited by a concentration of 相似文献   

LEADER Program results for 2009: an activity and spectrum analysis of linezolid using 6,414 clinical isolates from 56 medical centers in the United States

The LEADER Program monitors the in vitro activity of linezolid in sampled U.S. medical centers using reference broth microdilution methods with supporting molecular investigations in a central laboratory design. This report summarizes data obtained in 2009, the 6th consecutive year of this longitudinal study. A total of 6,414 isolates from 56 medical centers in all nine Census regions across the United States participated in 2009. For the six leading species/groups, the following linezolid MIC(90) values were observed: Staphylococcus aureus, 2 μg/ml; coagulase-negative staphylococci (CoNS), 1 μg/ml; Enterococcus spp., 2 μg/ml; Streptococcus pneumoniae, 1 μg/ml; viridans group streptococci, 1 μg/ml; and beta-hemolytic streptococci, 1 μg/ml. Linezolid resistance was only 0.34% overall, with no evidence of significant increase in the LEADER Program since 2006. The predominant linezolid resistant mechanism found was a G2576T mutation in the 23S rRNA. L3/L4 riboprotein mutations were also found. The mobile multidrug-resistant cfr gene was found in four strains (two S. aureus strains and one strain each of S. epidermidis and S. capitis) from four different states, suggesting persistence but a lack of dissemination. Linezolid continues to exhibit excellent activity and spectrum, and this study documents the need for continued monitoring of emerging mechanisms of resistance over a wide geographic area.     

LEADER Surveillance program results for 2010: an activity and spectrum analysis of linezolid using 6801 clinical isolates from the United States (61 medical centers)

The LEADER program monitors the in vitro activity of linezolid and comparator agents across the United States using reference broth microdilution and supportive molecular susceptibility-based investigations. This report summarizes the data from the 2010 program, the seventh consecutive year. A total of 61 medical centers from the USA including 7 medical centers specializing in children's healthcare provided a total of 6801 Gram-positive pathogens. The medical centers represented all 9 US Bureau of Census geographic regions. The organisms tested by reference broth microdilution were 3105 Staphylococcus aureus, 944 coagulase-negative staphylococci (CoNS), 934 Enterococci, 803 Streptococcus pneumoniae, 604 β-haemolytic streptococci, and 411 viridans group and other streptococci. The MIC(90) value for each of the above 6 targeted groups of organisms was 1 μg/mL. The "all organism" linezolid-resistant and nonsusceptible rate was 0.38%, which has been constant at 0.34% (2009) to 0.45% (2006) for the last 4 years. For Staphylococcus aureus, only 0.06% of the isolates were linezolid-resistant (MIC, ≥8 μg/mL); however, 2 additional methicillin-resistant Staphylococcus aureus had a cfr and a MIC of only 4 μg/mL. Resistance to linezolid was detected in 7 enterococci (0.75%) and 14 CoNS isolates (1.48%). This also represents a stable rate of resistance noted since the 2006 LEADER program report. Of note, for the first time in the 7 years of the Leader Program a linezolid-resistant Streptococcus pneumoniae was encountered. Overall, the results of the LEADER program demonstrate that linezolid maintains excellent in vitro activity against target Gram-positive pathogens across the USA. The LEADER program continues to provide valuable reference and molecular-level monitoring of linezolid activity.     

Zyvox Annual Appraisal of Potency and Spectrum Program Results for 2006: an activity and spectrum analysis of linezolid using clinical isolates from 16 countries

The Zyvox Annual Appraisal of Potency and Spectrum Program has completed its fifth year of monitoring for emerging resistance to linezolid and other Gram-positive active agents on the continents of Europe, Asia, Australia, and Latin America. In 2006, 4216 Gram-positive isolates from 16 nations were submitted for analysis from 6 organism groups including Staphylococcus aureus (54.0%), coagulase-negative staphylococci (CoNS) (14.6%), enterococci (10.0%), Streptococcus pneumoniae (9.4%), viridans group streptococci (5.0%), and beta-hemolytic streptococci (7.0%). Linezolid retained potent activity against S. aureus (MIC(50) and MIC(90), 2 microg/mL; 39.8% methicillin resistant) and CoNS (MIC(50) and MIC(90), 1 microg/mL; 74.3% methicillin resistant). Despite endemicity of vancomycin-resistant enterococci (up to 30.0%) in several nations, linezolid inhibited >99% of strains at 相似文献   

LEADER surveillance program results for 2006: an activity and spectrum analysis of linezolid using clinical isolates from the United States (50 medical centers)

Surveillance for emerging linezolid resistance among commonly occurring Gram-positive pathogens in the United States began with the 2002 ZAAPS program and more recently (2004) expanded as the LEADER program. The 2006 LEADER program processed 5374 strains from 50 medical centers (100 per site) located within the 9 US census regions; species and number tested by broth microdilution (% linezolid susceptible) included Staphylococcus aureus (2913, >99.9), coagulase-negative staphylococci (CoNSs) (808, 98.4), enterococci (547, 97.4), Streptococcus pneumoniae (546, 100.0), viridans group streptococci (189, 100.0), and beta-hemolytic streptococci (371, 100.0). In addition to 1 linezolid-nonsusceptible S. aureus, 3 strains were daptomycin-nonsusceptible, 4 were quinupristin/dalfopristin-intermediate, 2 were vancomycin-intermediate (vancomycin MIC values, 4 mug/mL), and all were methicillin-resistant S. aureus. Among the linezolid-resistant isolates (1 S. aureus, 13 CoNSs, 3 Enterococcus faecalis, and 10 Enterococcus faecium isolates), all but 3 Staphylococcus epidermidis isolates had the G2567T mutation. Overall, 99.55% of the tested 2006 LEADER program isolates remained susceptible to linezolid at current Clinical and Laboratory Standards Institute breakpoints.     

Susceptibility of a variety of clinical isolates to linezolid: a European inter-country comparison

Using standardized in vitro susceptibility tests, 3382 bacteria recently isolated from skin, blood or respiratory tract infections were analysed for their susceptibility to linezolid, a new oxazolidinone, and a number of comparator antibacterial agents. Isolates originated in France, Italy, Germany, Spain, Sweden, The Netherlands and the UK. Laboratories in each country independently conducted broth microdilution susceptibility tests using NCCLS methods and epsilonometry (Etest). Isolates of Gram-positive cocci tested in each laboratory included methicillin-susceptible and -resistant Staphylococcus aureus, methicillin-susceptible and -resistant Staphylococcus epidermidis, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae and Enterococcus spp. Isolates of Moraxella catarrhalis and Haemophilus influenzae were also included. Where appropriate, comparator drugs (oxacillin, vancomycin, gentamicin, co-amoxiclav, ciprofloxacin, erythromycin, penicillin G, clindamycin and ampicillin) were also tested. Linezolid demonstrated excellent activity against all of the Gram-positive cocci with MIC50s ranging from 0.5 to 4 mg/L. The drug demonstrated only modest activity against M. catarrhalis and H. influenzae with MIC50s ranging from 4 to 16 mg/L.     

Antimicrobial activity of a novel peptide deformylase inhibitor, LBM415, tested against respiratory tract and cutaneous infection pathogens: a global surveillance report (2003-2004)

OBJECTIVES: To evaluate the spectrum of activity and potency of LBM415, the first of the peptide deformylase inhibitor (PDFI) class to be developed for treatment of community-acquired respiratory tract infections and uncomplicated skin and soft tissue infections (uSSTI), against a large, contemporary international collection of targeted pathogens collected during 2003-2004. METHODS: A total of 21,636 isolates were tested by reference broth microdilution methods as part of a longitudinal international antimicrobial resistance surveillance study. Characteristics of the organism collection included resistance to oxacillin among 35.0% of Staphylococcus aureus and 76.0% of coagulase-negative staphylococci (CoNS); resistance to penicillin (MIC > or = 2 mg/L) among 18.0% of Streptococcus pneumoniae; vancomycin resistance among 20.0% of Enterococcus spp. and ampicillin resistance among 22.0% of Haemophilus influenzae. RESULTS: LBM415 displayed potent activity against staphylococci, streptococci, Enterococcus faecium and Moraxella catarrhalis, with > or = 99.0% of strains being inhibited at < or = 4 mg/L; 97.0% of Enterococcus faecalis isolates and 92.0% of H. influenzae isolates were also inhibited at this concentration. Seventy-seven percent of Burkholderia cepacia and 82.0% of Stenotrophomonas maltophilia were inhibited at < or = 8 mg/L. No differences in LBM415 activity against S. aureus, CoNS, S. pneumoniae, Enterococcus spp. and H. influenzae were detected for subsets susceptible or resistant to antimicrobials such as oxacillin, penicillin, ampicillin, macrolides, vancomycin and fluoroquinolones. While regional differences were apparent with some comparator agents, sensitivity to LBM415 did not vary significantly among strains from the various geographic areas sampled. One isolate of S. aureus displayed high-level resistance to LBM415 owing to multiple sequence changes in resistance phenotype genes (defB and fmt), despite the absence of the compound in clinical practice. This isolate remained susceptible to all other antimicrobials tested except for penicillin. CONCLUSIONS: With few differences detected among strains from various geographic regions, the first PDFI class agent to enter clinical development has consistently demonstrated a broad spectrum of activity against commonly isolated pathogens associated with uncomplicated respiratory and cutaneous infections. These compounds represent a significant therapeutic advance owing to their novel mechanism of action and antibacterial spectrum, including activity against resistant organisms, should pharmacokinetic and pharmacodynamic parameters support their continued development. Given the detection of a pre-existing PDFI-resistant isolate of S. aureus as demonstrated here, surveillance for resistance among the PDFI-targeted pathogens following introduction of this class of agent into clinical usage will be an important component of future studies.     

A multicenter evaluation of linezolid antimicrobial activity in North America

Overall, 141 centers in North America enrolled in this international surveillance study designed to evaluate the in vitro antimicrobial activity and spectrum of linezolid, a new oxazolidinone. Each participant tested the susceptibility of clinical isolates of staphylococcal species (n = 85) against 12 drugs, and enterococcal species (n = 40) against 6 drugs using reference broth microdilution trays; and of streptococcal species (n = 25) against 6 drugs using Etests (AB BIODISK, Solna, Sweden). Quality control testing was conducted using recommended strains, and verification of resistance to linezolid and select other agents was performed by a regional monitor. Of the 20,161 isolates collected from sites across the United States (US; n = 132) and Canada (n = 9), 18,307 were included in this analysis. Oxacillin resistance occurred in 38.7 and 70.6% of Staphylococcus aureus and coagulase-negative staphylococcal (CoNS) isolates, respectively. Vancomycin resistance was reported in 65.9 and 2.6% of Enterococcus faecium and E. faecalis, respectively. Penicillin resistance occurred in 37.2% of Streptococcus pneumoniae, 17.5% constituting high-level resistance (MIC, > or =2 microg/ml). The MIC(90) for linezolid was 1 microg/ml for streptococci, 2 microg/ml for enterococci and CoNS isolates, and 4 microg/ml for S. aureus. Using the US FDA-recommended susceptible breakpoints for linezolid, there were no confirmed reports of linezolid resistance (i.e., MIC > or =8 microg/ml). The occurrence of linezolid MICs was unimodal and generally varied between, 1-4 microg/ml for staphylococci (94% of recorded results), 1-2 microg/ml for enterococci (93%), and 0.5-1 microg/ml for streptococci (85%). Susceptibility to linezolid was not influenced by susceptibility to other antiicrobials such as vancomycin, beta-lactams or macrolides. Only linezolid was universally active against essentially all tested Gram-positive specimens. The unimodal susceptibility pattern is indicative of excellent and near complete activity against key Gram-positive pathogens including multiply resistant strains, but surveillance for emerging resistances (rare) and the performance of routine susceptibility tests to guide patient therapy seems prudent.     

Oxazolidinone susceptibility patterns in 2004: report from the Zyvox Annual Appraisal of Potency and Spectrum (ZAAPS) Program assessing isolates from 16 nations

OBJECTIVES: To investigate the activity of linezolid (an oxazolidinone), a potent choice for community- and hospital-acquired infections, via a worldwide surveillance network called the Zyvox Annual Appraisal of Potency and Spectrum (ZAAPS) Program. METHODS: A total of 4098 Gram-positive strains were collected from 42 laboratories located in North America (five sites in Canada), South America (10 sites), Europe (16 sites) and the Far East (11 sites). Each country or site submitted 200 isolates (Canada submitted 200 isolates for each of five sites; total 1000) for confirmation of organism identification and reference MIC processing. Nearly 25 comparator agents were tested along with quality control strains, and interpretative criteria from the CLSI, formerly the NCCLS, M100-S15 were applied. No linezolid resistance was detected in strains from 16 monitored countries in 2004. RESULTS: Linezolid remained highly active against Streptococcus pneumoniae, viridans group and beta-haemolytic streptococci (MIC90, 1 mg/L). Against Staphylococcus aureus, linezolid showed 99.5% of results at 0.5-2 mg/L with only one isolate at 4 mg/L. Oxacillin-resistant S. aureus rates varied between nations and ranged from 1.4% in Sweden to 29.5% in the UK to 65.2% in Mexico. Linezolid MIC values were generally one log2 dilution step lower for coagulase-negative staphylococci (CoNS) when compared with S. aureus. No CoNS strains produced a linezolid result at 4 mg/L. Compared with ZAAPS 2002 and 2003 results for enterococci where seven resistant strains were identified, the 2004 data revealed no resistance and 98.1% of linezolid MIC results were at 1 or 2 mg/L. Vancomycin-resistant enterococci (5.3% overall) varied markedly by country including a high of 47.2% in Korea. CONCLUSIONS: Linezolid continues to be effective in vitro against Gram-positive pathogens from five continents and no oxazolidinone-resistant strains were identified among the 4098 systemically collected strains (2004) or among 20 158 non-United States isolates for the entire ZAAPS Program (2002-04).     

In vitro activities of ertapenem (MK-0826) against recent clinical bacteria collected in Europe and Australia

Ertapenem (MK-0826, L-749,345) is a 1-beta-methyl carbapenem with a long serum half-life. Its in vitro activity was determined by broth microdilution against 3,478 bacteria from 12 centers in Europe and Australia, with imipenem, cefepime, ceftriaxone, and piperacillin-tazobactam used as comparators. Ertapenem was the most active agent tested against members of the family Enterobacteriaceae, with MICs at which 90% of isolates are inhibited (MIC(90)s) of < or =1 microg/ml for all species. Ertapenem also was more active than imipenem against fastidious gram-negative bacteria and Moraxella spp.; on the other hand, ertapenem was slightly less active than imipenem against streptococci, methicillin-susceptible staphylococci, and anaerobes, but its MIC(90)s for these groups remained < or =0.5 microg/ml. Acinetobacter spp. and Pseudomonas aeruginosa were also much less susceptible to ertapenem than imipenem, and most Enterococcus faecalis strains were resistant. Ertapenem resistance, based on a provisional NCCLS MIC breakpoint of > or =16 microg/ml, was seen in only 3 of 1,611 strains of the family Enterobacteriaceae tested, all of them Enterobacter aerogenes. Resistance was also seen in 2 of 135 anaerobes, comprising 1 Bacteroides fragilis strain and 1 Clostridium difficile strain. Ertapenem breakpoints for streptococci have not been established, but an unofficial susceptibility breakpoint of < or =2 microg/ml was adopted for clinical trials to generate corresponding clinical response data for isolates for which MICs were as high as 2 microg/ml. Of 234 Streptococcus pneumoniae strains tested, 2 required ertapenem MICs of 2 microg/ml and one required an MIC of 4 microg/ml, among 67 non-Streptococcus pyogenes, non-Streptococcus pneumoniae streptococci, single isolates required ertapenem MICs of 2 and 16 microg/ml. These streptococci also had diminished susceptibilities to other beta-lactams, including imipenem as well as ertapenem. The Etest and disk diffusion gave susceptibility test results in good agreement with those of the broth microdilution method for ertapenem.     

Spectrum and potency of dalbavancin tested against 3322 Gram-positive cocci isolated in the United States Surveillance Program (2004)

Dalbavancin is an injectable, next generation lipoglycopeptide with an extended serum elimination half-life. Once-weekly dosing has been successful for treatment of skin and skin structure (SSSI) and catheter-related bloodstream infections (CR-BSI). Concurrent with clinical trails, dalbavancin resistance surveillance was initiated in 2003, and results are reported here for the 2004 United States (USA) component. A total of 3322 Gram-positive cocci were tested by reference broth microdilution methods. Organism species tested included: Staphylococcus aureus (2102; 49% oxacillin-resistant), coagulase-negative staphylococci (CoNS; 255, 82% oxacillin-resistant), beta-hemolytic streptococci (241), viridans group streptococci (46), and Streptococcus pneumoniae (678). Dalbavancin (MIC90,0.06-0.12 microg/mL) was comparable in spectrum, but superior in potency to vancomycin (MIC90,1-2 microg/mL) against staphylococci. Dalbavancin MIC90 values against the tested streptococci was 0.03 microg/mL. Dalbavancin was more active against tested SSTI pathogens than comparator agents having complete susceptibility rates (100.0%) similar to vancomycin. Vancomycin, (16- to 32-fold), linezolid (8- to 32-fold), daptomycin (4- to 32-fold), and quinupristin/dalfopristin (4- to 32-fold) were less active than dalbavancin. In conclusion, dalbavancin exhibited greater potency than comparison glycopeptides or lipopeptides, streptogramin combinations, and oxazolidinones against Gram-positive pathogens associated with SSSI or CR-BSI. Dalbavancin wild-type MIC distributions remain unchanged compared with prior sampled years (2002-2003) in the USA.     

In vitro activity of gemifloxacin against a broad range of recent clinical isolates from the USA

The antibacterial potencies of gemifloxacin (SB-265805) and 13 comparator compounds were determined by broth microdilution against a panel of 645 Gram-positive and 995 Gram-negative organisms collected from various USA sites. Time-kill studies were performed and postantibiotic effect (PAE) was determined for several organisms using trovafloxacin and ciprofloxacin as comparator compounds. Based on MIC(90)s, gemifloxacin was the most potent compound tested against Gram-positive isolates: Streptococcus pneumoniae (MIC(90) 0. 016 mg/L), Streptococcus agalactiae (0.03 mg/L), Streptococcus pyogenes (0.03 mg/L), viridans streptococci (0.12 mg/L), methicillin-susceptible Staphylococcus aureus (0.03 mg/L), Staphylococcus epidermidis (2 mg/L), Staphylococcus saprophyticus (0. 016 mg/L) and Enterococcus faecalis (2 mg/L). Against Gram-negative isolates, the potency of gemifloxacin was equal to that of levofloxacin and ciprofloxacin and generally better than that of ofloxacin, grepafloxacin, trovafloxacin and nalidixic acid. MIC(90)s for gemifloxacin were: Haemophilus influenzae (6 h at 4 x MIC) and shorter PAEs with E. faecalis (0.1-0.6 h) and K. pneumoniae (0.1-0.2 h). In conclusion, gemifloxacin is a novel quinolone with a broad spectrum of antimicrobial activity. It has substantially improved potency against Gram-positive organisms, especially streptococci, for which gemifloxacin is generally at least eight- to 16-fold more potent than other quinolones tested. It retains the good Gram-negative activity seen with ciprofloxacin and levofloxacin and shows good bactericidal activity and prolonged PAEs.     

Activity of dalbavancin against staphylococci and streptococci, assessed by BSAC and NCCLS agar dilution methods

BACKGROUND: Dalbavancin is a long-half-life (9-12 days) glycopeptide, now in Phase 3 development. Its pharmacokinetics may facilitate home intravenous therapy, early discharge and long prophylaxis. METHODS: Dalbavancin and comparators were tested in vitro against staphylococci and streptococci to determine (i) activity and (ii) the comparability of agar dilution MICs by the BSAC and the NCCLS methods. The test panels comprised 92-93 isolates each of Staphylococcus aureus, coagulase-negative staphylococci (CoNS) and 'viridans' streptococci, chosen for epidemiological diversity and to over-represent strains resistant to conventional agents, including teicoplanin. RESULTS: Dalbavancin MICs by the BSAC and NCCLS methods generally were identical, or else those by the BSAC method were two-fold lower. In both cases the MIC distributions of dalbavancin within species groups were unimodal, with peaks at 0.25, 0.12/0.25 and 0.12 mg/L for S. aureus, CoNS and viridans streptococci, respectively. MIC differences between the BSAC and NCCLS methods were similarly small for other glycopeptides and, generally, non-glycopeptides. Dalbavancin MICs were mostly two- to 16-fold below those of vancomycin and dalbavancin-like vancomycin-remained highly active against teicoplanin-non-susceptible staphylococci. CONCLUSIONS: Dalbavancin has good activity versus streptococci and staphylococci, including teicoplanin-resistant strains. MICs by BSAC and NCCLS agar dilution methods were comparable to each other; slightly lower MIC values, nevertheless, have been recorded by broth microdilution.     

Comparative activities of daptomycin and several agents against staphylococcal blood isolates. Glycopeptide tolerance

The activity of daptomycin was evaluated against 702 staphylococcal blood isolates (316 methicillin-susceptible Staphylococcus aureus, 187 methicillin-resistant S. aureus [MRSA], and 199 coagulase-negative staphylococci [CoNS]) collected in 41 Spanish hospitals. Glycopeptide tolerance and the incidence of heterogeneous glycopeptide-intermediate (hGISA) isolates were also examined. Vancomycin MICs determined by the Etest were compared with those obtained by the reference broth microdilution method. Daptomycin exhibited good activity, and only 2 isolates were nonsusceptible to this antibiotic. Resistance to linezolid was observed in 2 MRSA isolates and in 16 CoNS. The cfr gene was detected in 7 of these 18 isolates. Vancomycin and teicoplanin tolerance was 9.6% and 21.9%, respectively, in MRSA isolates. We detected the hGISA phenotype in 5.8% of MRSA isolates. Vancomycin MICs by the Etest were slightly higher than those obtained by broth microdilution. Daptomycin retained activity against isolates that were not susceptible to linezolid, teicoplanin, or quinupristin-dalfopristin.     

BMS284756 (formerly T-3811, a des-fluoroquinolone) potency and spectrum tested against over 10,000 bacterial bloodstream infection isolates from the SENTRY antimicrobial surveillance programme (2000)

BMS284756 is a novel des-F (6)-quinolone, which has a wide range of activity against many species of Gram-positive and -negative organisms. The potency of BMS284756 was compared with that of other quinolones, including ciprofloxacin, gatifloxacin and levofloxacin, and was tested against >10,000 bloodstream isolates from the year 2000 SENTRY antimicrobial surveillance programme. Twelve pathogens accounted for nearly all of the referred isolates and included Staphylococcus aureus, coagulase-negative staphylococci, Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Serratia spp., Pseudomonas aeruginosa, Acinetobacter spp., Enterococcus spp., Streptococcus pneumoniae and beta-haemolytic or viridans group streptococci. Of the four quinolones tested, BMS284756 was the most active overall against Staphylococcus spp. (MIC(50) < or = 0.03 mg/L) and Streptococcus spp. (MIC(50) 0.06 mg/L). In contrast, BMS284756 was less potent than the other quinolones against the enteric Gram-negative bacilli (MIC(50) < or = 0.03-1 mg/L). With a proposed breakpoint of < or =4 mg/L, BMS284756 may be a therapeutic alternative pending the results of clinical trials.     

Comparative antimicrobial activity of gatifloxacin tested against Streptococcus spp. including quality control guidelines and etest method validation. Quality Control Study Group.

Gatifloxacin (formerly AM-1155 or CG 5501) is a new 8-methoxy fluoroquinolone with enhanced activity against Gram-positive cocci, especially Streptococcus pneumoniae and other streptococci. Recent clinical strains (599 isolates) were tested against gatifloxacin, three comparison fluoroquinolones, and penicillin by the reference broth microdilution, Etest (AB BIODISK, Solna, Sweden) and standardized disk diffusion methods (5 micrograms gatifloxacin disk). Gatifloxacin (MIC90, 0.5 microgram/ml) activity was generally comparable to that of trovafloxacin (MIC90, 0.25 microgram/ml), or sparfloxacin (MIC90, 0.5 microgram/ ml) and markedly superior to ofloxacin (MIC90, 2-4 micrograms/ml) against the streptococci. Rates of penicillin non-susceptibility were 41.9, 38.0, and 16.2% for S. pneumoniae (301 strains), viridans group streptococci (150 strains), and beta-haemolytic streptococci (148 strains). Etest results correlated well (95.7-100.0% +/- one log2 dilution) with the reference MIC results, but Etest tended to have elevated gatifloxacin MIC results compared to the broth microdilution method for the highly resistant isolates (MICs, > 2 micrograms/ml). Gatifloxacin disk zone diameters correlate well to reference MICs for all streptococci and proposed interpretive criteria (susceptible at < or = 1 microgram/ml or > or = 18 mm, and resistant at > or = 4 micrograms/ml or < or = 14 mm) did not produce discords between method results (absolute agreement). A nine laboratory quality control (QC) study conforming to the National Committee for Clinical Laboratory Standards (NCCLS) Guideline M23-T3 studied S. pneumoniae ATCC 49619 and gatifloxacin. Proposed ranges for QC of NCCLS tests were 0.12-0.5 microgram/ml for the broth microdilution test and 24-31 mm for the disk diffusion method. These reported results indicate that gatifloxacin was a potent fluoroquinolone with extensive activity against streptococcal isolates. In vitro test methods to measure this activity appear accurate and comparable; and QC guidelines have been established for routine clinical laboratory use pending approval by the NCCLS and the Food and Drug Administration (FDA).     

Potential utility of a peptide deformylase inhibitor (NVP PDF-713) against oxazolidinone-resistant or streptogramin-resistant Gram-positive organism isolates

OBJECTIVES: To evaluate the potency of a novel peptide deformylase inhibitor, NVP PDF-713, against Gram-positive organisms having resistances to linezolid or quinupristin/dalfopristin. MATERIALS AND METHODS: A total of 45 strains from three genera (six species groups) were tested by reference broth microdilution methods. The mechanism of resistance to the oxazolidinone was determined by sequencing of the gene encoding the ribosomal target. RESULTS: NVP PDF-713 retained activity against linezolid-resistant staphylococci (MIC range 0.25-2 mg/L), Streptococcus oralis (MIC 0.5 mg/L), Enterococcus faecalis (MIC range 2-4 mg/L) and Enterococcus faecium (MIC range 0.5-4 mg/L). Quinupristin/dalfopristin-resistant E. faecium (MIC range 1-2 mg/L) and staphylococci (MIC range 0.12-2 mg/L) were also inhibited by NVP PDF-713. Many (10 of 13 strains) of the linezolid-resistant enterococci were resistant to vancomycin and these clinical strains had a G2576U ribosomal target mutation. CONCLUSIONS: NVP PDF-713 appears to be a promising clinical candidate among the peptide deformylase inhibitors for the treatment of infections caused by Gram-positive organisms that possess resistances to oxazolidinones or streptogramin combinations.     

In vitro antibacterial activity of the peptide deformylase inhibitor BB-83698

OBJECTIVES: BB-83698 is a peptide deformylase inhibitor currently in clinical trials in Europe. The purpose of this study was to provide additional susceptibility data from clinical isolates, including drug-resistant strains. METHODS: The in vitro activities of BB-83698 and comparators were determined against 281 streptococci, 154 Staphylococcus aureus, 110 Haemophilus influenzae and 50 Moraxella catarrhalis strains selected for their resistance phenotypes. Broth microdilution MICs and MBCs were determined according to NCCLS guidelines. RESULTS: The MIC90s were 0.25-0.5 mg/L for S. pneumoniae, including penicillin-, erythromycin-, levofloxacin- and multidrug-resistant strains. The MIC90s for Streptococcus pyogenes and Streptococcus agalactiae were 0.12 mg/L and for viridans streptococci, the MIC90 was 0.5 mg/L. Against S. aureus, including oxacillin- and levofloxacin-resistant strains, and vancomycin-intermediate strains, the MIC90 was 8 mg/L. Against beta-lactamase-negative and -positive H. influenzae, the MIC90s were 32 and 64 mg/L, respectively, and against both beta-lactamase-negative and -positive M. catarrhalis the MIC90 was 0.12 mg/L. In MBC studies, the ratio of MBC/MIC was 1:1 or 2:1 against 31% of S. pneumoniae, 33% of S. aureus, 63% of H. influenzae and 9% of M. catarrhalis. CONCLUSIONS: Although BB-83698 has reduced in vitro activity against H. influenzae, it is a potent antimicrobial with excellent activity against streptococci and Moraxella.     

Geographic variations in garenoxacin (BMS284756) activity tested against pathogens associated with skin and soft tissue infections: report from the SENTRY Antimicrobial Surveillance Program (2000)

The antimicrobial activity of garenoxacin, a des-(6)F quinolone (formally BMS284756 and T-3811), was evaluated against 2,537 skin and soft tissue infection (SSTI) isolates from the SENTRY Antimicrobial Surveillance Program. Strains isolated in 2000 from Europe, North and Latin America were tested at a central laboratory using reference broth microdilution methods. The rank order of the seven most frequent SSTI pathogens was: Staphylococcus aureus (39.9%), Pseudomonas aeruginosa (12.1%), Escherichia coli (9.7%), Enterococcus spp. (7.7%), Klebsiella spp. (5.8%), Enterobacter spp. (5.6%) and coagulase-negative staphylococci (CoNS; 4.2%). Garenoxacin exhibited a four-fold greater activity (MIC(90), 0.06 microg/ml) compared to levofloxacin (MIC(90), 0.25 microg/ml) against oxacillin-susceptible S. aureus; and oxacillin-resistant staphylococci were more susceptible to garenoxacin (>/=90.5%) at Europe > North America). Continued development of garenoxacin as a treatment of pathogens that commonly cause SSTIs appears to be warranted.     

Tigecycline activity tested against 26,474 bloodstream infection isolates: a collection from 6 continents

The activity of tigecycline (formerly GAR936), a novel glycylcycline, was tested against recent bloodstream infection (BSI) pathogen isolates from 6 continents. Frequency of clinical occurrence of these pathogens was determined and their antibiograms assessed using reference broth microdilution methods. A total of 26474 strains were tested for tigecycline susceptibility according to the Clinical and Laboratory Standards Institute (formerly the National Committee for Clinical Laboratory Standards) by the M7-A6 guidelines with interpretations from M100-S15 and the package insert. The rank order of pathogens was Staphylococcus aureus (33.1%), Escherichia coli (14.0%), coagulase-negative staphylococci (13.5%), Enterococcus spp. (12.3%), Klebsiella spp. (5.7%), Pseudomonas aeruginosa (4.2%), Enterobacter spp. (3.0%), beta-hemolytic streptococci (2.9%), Streptococcus pneumoniae (2.3%), and viridans group streptococci (1.4%). Tigecycline exhibited a broader spectrum of activity against BSI isolates when compared to ciprofloxacin, tetracycline, aminoglycosides, and many beta-lactams (imipenem). Tigecycline was highly active against most pathogens tested, including staphylococci (MIC(90), 0.5 microg/mL), enterococci (MIC90, 0.25 microg/mL), streptococci (MIC(90), < or =0.12 microg/mL), Escherichia coli (MIC90, 0.25 microg/mL), Klebsiella spp. (MIC90, 1 mmicrog/mL), and Enterobacter spp. (MIC(90), 2 mmicrog/mL), but showed limited inhibition of Pseudomonas aeruginosa (MIC90, 16 microg/mL) and indole-positive or indole-negative Proteae (MIC90, 4-8 microg/mL). In summary, tigecycline exhibited a wide spectrum of antimicrobial potency versus BSI isolates collected worldwide. Serious infections in nosocomial environments should benefit from tigecycline use among the investigational phase 3 agents focused toward resistant strains.