Three independent yearly analyses of the spectrum and potency of metronidazole: a multicenter study of 1,108 contemporary anaerobic clinical isolates.

To comply with ongoing United States Food and Drug Administration (FDA) recommendations about the validation of prescribing information, in each of three years (1994, 1996, 1997) at six medical centers, metronidazole was tested against > or = 50 strains of a range of contemporary anaerobic clinical bacteria. Species having > or = 90% susceptibility (MIC, < or = 8 microg/ml) to metronidazole (fulfilling FDA requirements) included Bacteroides fragilis, B. distasonis, B. ovatus, B. thetaiotaomicron, B. vulgatus, Fusobacterium spp. and Clostridium spp. Only Eubacterium spp. and anaerobic Gram-negative cocci failed to achieve the required proportion of susceptibility throughout the 3 year period. Metronidazole appears to remain highly active versus anaerobic species associated with strict anaerobic organisms.

Evaluation of gemifloxacin (SB-265805, LB20304a): in vitro activity against over 6000 gram-positive pathogens from diverse geographic areas.

Gemifloxacin (GEMI), formerly SB-265805 and LB20304, is a newer fluoroquinolone with broad-spectrum activity against a wide variety of bacterial pathogens. The present investigation extended earlier observations by sampling an additional 6790 gram-positive organisms from more than 50 medical centres on three continents. The reference broth microdilution method with recommended medium supplements was used throughout. Selected results (number strains tested; MIC90 for GEMI/trovafloxacin in mg/l; % < or = 1 mg/l for GEMI/trovafloxacin) were: Staphylococcus aureus (3672; 2/2; 86/85), S. epidermidis (404; 1/>4; 92/71), Enterococcus faecalis (630; 4/>4; 76/66), E. faecium (216; > 4/>4; 15/11), Streptococcus pneumoniae (300; 0.06/0.25; 100/97), beta-haemolytic streptococci (150; 0.06/0.25; 100/100) and viridans group streptococci (150; 0.12/0.25; 99/97). Gemifloxacin appeared equal or superior to trovafloxacin in its overall gram-positive spectrum of activity pending a choice of the susceptible breakpoint concentration. Continued in vitro, pharmacodynamic and clinical investigations of gemifloxacin appear warranted.

Development of gemifloxacin in vitro susceptibility test methods for gonococci including quality control guidelines. The Quality Control Study Group.

Gemifloxacin (formerly SB-265805 or LB20304a) is a new fluoronapthyridone with documented activity against Gram-positive and -negative organisms. The activity of gemifloxacin was tested against 150 Neisseria gonorrhoeae strains, using reference agar dilution, standardized disk diffusion, and Etest (AB BIODISK, Solna, Sweden) methods. Gemifloxacin was very potent against ciprofloxacin (CIPRO)-susceptible strains (MIC(90,) 0.008 microg/ml) but was significantly less active against the CIPRO-resistant gonococci (MIC(90,) 0.12 microg/ml). Etest and reference agar dilution MIC results showed excellent correlation (r = 0.96), and 98.7% MICs were within +/- one log(2) dilution. Agar dilution MICs were also compared to zone diameters obtained using gemifloxacin 5-microg disks; and complete intermethod categorical agreement (100%) was achieved applying breakpoints proposed as follows: < or =0.25 microg/ml (zone, > or =25 mm) for susceptible and > or =1 microg/ml (zone, < or =21 mm) for resistant. Gemifloxacin MIC and disk diffusion te quality control (QC) ranges were established for N. gonorrhoeae ATCC 49226. Data were collected from > or = seven laboratories, three GC agar medium lots for both agar MICs and disk methods, and two lots each of the 5- and 10-microg disks. The proposed MIC QC range was 0.002 to 0.016 microg/ml and the calculated mm zone ranges (median +/- 0.5x average mm range) for both disks were similar, but contained only 88.1 to 91.9% of participant results. To achieve the acceptable > or = 95% of all study results within range, a 43 to 54 mm limits (5-microg disks) were necessary. The excellent broad-spectrum activity and a low reported adverse effects profile of gemifloxacin shows a potential for treatment of fluoroquinolone-resistant gonorrhea.

Anti-gonococcal activity of gemifloxacin against fluoroquinolone-resistant strains and a comparison of agar dilution and Etest methods.

Gemifloxacin is a novel quinolone with excellent activity against Gram-positive and some Gram-negative pathogens. Its activity was tested against 150 Neisseria gonorrhoeae strains, including 50 ciprofloxacin-resistant isolates, using reference agar dilution and Etest methods. Gemifloxacin was found to be highly potent against ciprofloxacin-susceptible strains (MIC(90) 0.008 mg/L), but was 16-fold less potent against ciprofloxacin-resistant gonococci. The order of quinolone potency against these fluoroquinolone-resistant mutants was: gemifloxacin (MIC(90) 0.12 mg/L) > trovafloxacin (0.25 mg/L) > moxifloxacin = grepafloxacin (0.5 mg/L) > ciprofloxacin (1 mg/L). Etest and reference agar dilution MIC results showed excellent correlation (r = 0.96) and >98% of MICs were within +/-1 log(2) dilution step (essential agreement). The excellent potency of gemifloxacin indicates its potential for the treatment of infections with quinolone-resistant N. gonorrhoeae.

Quality control guidelines for disk diffusion and broth microdilution antimicrobial susceptibility tests with seven drugs for veterinary applications.

This multicenter study proposes antimicrobial susceptibility (MIC and disk diffusion methods) quality control (QC) parameters for seven compounds utilized in veterinary health. Alexomycin, apramycin, tiamulin, tilmicosin, and tylosin were tested by broth microdilution against various National Committee for Clinical Laboratory Standards (NCCLS)-recommended QC organisms (Staphylococcus aureus ATCC 29213, Enterococcus faecalis ATCC 29212, Streptococcus pneumoniae ATCC 49619, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853). In addition, disk diffusion zone diameter QC limits were determined for apramycin, enrofloxacin, and premafloxacin by using E. coli ATCC 25922, P. aeruginosa ATCC 27853, and S. aureus ATCC 25923. The results from five or six participating laboratories produced >/=99.0% of MICs and >/=95.0% of the zone diameters within suggested guidelines. The NCCLS Subcommittee for Veterinary Antimicrobial Susceptibility Testing has recently approved these ranges for publication in the next M31 document.

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).

Comparative antimicrobial activity of gatifloxacin tested against Campylobacter jejuni including fluoroquinolone-resistant clinical isolates.

Campylobacter jejuni is an important pathogen that causes gastroenteritis, as well as other disease states such as meningitis and septic arthritis. In this study, the Etest (AB BIODISK, Solna, Sweden) results were compared to a reference agar dilution method using gatifloxacin, a new 8-methoxyfluoroquinolone. A total of 53 strains of C. jejuni initially isolated from patients in California and Mexico were tested. Results demonstrated a high correlation (r = 0.88) between the two utilized in vitro dilution methods. In addition, gatifloxacin activity was compared to that of ciprofloxacin, metronidazole, amoxicillin, erythromycin, chloramphenicol, gentamicin, tetracycline, and trimethoprim/sulfamethoxazole using the Etest. Gatifloxacin (MIC90, 4 micrograms/ml) was approximately eight- to 16-fold more potent than ciprofloxacin (Mic90, > 32 micrograms/ml), a commonly used fluoroquinolone for Campylobacter infections. Eight strains highly resistant to ciprofloxacin (MIC90, > 32 micrograms/ml) were tested for cross resistance against the newer fluoroquinolones (gatifloxacin, levofloxacin, trovafloxacin) and the rank order of potency was: gatifloxacin (MIC50, 16 micrograms/ml) > trovafloxacin = levofloxacin (MIC50, > 32 micrograms/mL). However, only 25% ciprofloxacin-resistant strains were inhibited by < or = 1 microgram/mL of gatifloxacin or trovafloxacin. These results for gatifloxacin against C. jejuni strains must be further assessed in the context of in vivo trials before the clinical role of this new fluoroquinolone can be determined. The Etest appears to be a simple and precise susceptibility test method for testing C. jejuni isolates against fluoroquinolones and other alternative therapeutic agents.

Antimicrobial activity and spectrum of SCH27899 (Ziracin) tested against gram-positive species including recommendations for routine susceptibility testing methods and quality control. Quality Control Study Group.

SCH27899 is an oligosaccharide, everninomicin antibiotic with activity primarily against Gram-positive pathogens. The activity of SCH27899 was evaluated against 360 routine clinical isolates by the broth microdilution (BMD), agar dilution (AD), disk diffusion (DD), and Etest (AB BIODISK, Solna, Sweden) methods. In addition, results from a nine center SCH27899 quality control (QC) trial were used to establish QC ranges. SCH27899 MICs for 330 Gram-Positive strains, including multiply-resistant staphylococci and enterococci, ranged from 0.015 to 1 microgram/ml with MIC90s of 0.12 to 0.5 microgram/ ml. SCH27899 had no measurable activity against the 30 selected Gram-negative strains tested (MICs, > 256 micrograms/ml), with the exception of Moraxella catarrhalis MICs, 0.12 microgram/ ml). Etest MICs for SCH27899 correlated well with AD and BMD results with > 90% of MICs within +/- one log2 dilutions of the reference test results. Three disk concentrations (2.5-, 5-, 10-microgram) of SCH27899 were evaluated, but minimal difference of zone diameters between disk drug contents was observed (+/- 2 mm). SCH27899 disk zone diameters correlated poorly with reference MICs due to small zone diameters (range, 11 to 22 mm) attributed to poor diffusion through agar mediums, a product of this compound's high molecular weight and solubility. The use of the DD method for SCH27899 was not recommended. The proposed MIC quality assurance limits for SCH27899 using Staphylococcus aureus ATCC 29213 and Enterococcus faecalis ATCC 29212 was 0.06 to 0.25 microgram/ml for both QC strains and methods. SCH27899 appears to be a eveminomicin-derivative widely active against important Gram-positive cocci, and in vitro dilution testing methods would be preferred for clinical use, validated by the recommended MIC control ranges cited in this report.

Activity of gatifloxacin against Haemophilus influenzae and Moraxella catarrhalis, including susceptibility test development, E-test comparisons, and quality control guidelines for H. influenzae.

In vitro antimicrobial activity and susceptibility testing interpretation criteria and quality control were studied for gatifloxacin, a new 8-methoxy fluoroquinolone, tested against Haemophilus influenzae. Moraxella catarrhalis (600 strains) and H. influenzae (1,400 strains) from the SENTRY Antimicrobial Surveillance Program in North America (Canada and the United States) were also tested against gatifloxacin and 12 other antimicrobial agents. Gatifloxacin (MIC at which 90% of the isolates are inhibited [MIC90], /=18 mm) was also suggested for H. influenzae testing. No interpretive errors were observed. Quality control guidelines for H. influenzae ATCC 49247 were determined by using the NCCLS M23-T3 (1998) study design. The results from the nine-laboratory protocol suggested the following control ranges: for broth microdilution tests, 0.004 to 0.03 microg/ml; for disk diffusion testing, 33 to 41 mm. Gatifloxacin appears to be a potent anti-Haemophilus fluoroquinolone compound with in vitro testing interpretive criteria that will produce accurate results (disk diffusion, broth microdilution, and E-test).

Gatifloxacin (AM-1155, CG 5501) susceptibility testing interpretive criteria and quality control guidelines for dilution and disk (5-microgram) diffusion methods. The Quality Control Study Group.

Gatifloxacin (formerly AM-1155 and CG5501), a new 8-methoxy fluoroquinolone, has an expanded spectrum of activity against Gram-positive cocci and some anaerobic bacteria. This compound was tested against 600 recent clinical strains of rapidly growing aerobic species to establish susceptibility testing interpretive criteria for the reference broth microdilution and standardized disk (5-microgram) diffusion methods of the National Committee for Clinical Laboratory Standards (NCCLS). These strains included 285 Enterobacteriaceae (17 species), 165 staphylococci, 49 enterococci, and 101 nonfermentative Gram-negative bacilli. Based on achievable serum levels with projected gatifloxacin dosing regimens, MIC break points of < or = 2 micrograms/mL (> or = 18 mm) for susceptibility and > or = 8 micrograms/mL (< or = 14 mm) for resistance were selected. The absolute agreement between tests was 94.3% with no very major false-resistant errors. The quality control ranges (MIC and zone diameters) for the NCCLS recommended strains were determined in a nine-laboratory NCCLS protocol as follows: Escherichia coli ATCC 25922 = 0.008-0.03 microgram/mL and 31-37 mm; Enterococcus faecalis ATCC 29212 = 0.12-1 microgram/mL; Pseudomonas aeruginosa ATCC 27853 = 0.5-2 micrograms/ml and 21-27 mm; Staphylococcus aureus ATCC 25923 = 27-33 mm and S. aureus ATCC 29213 = 0.03-0.12 microgram/mL. Gatifloxacin appears to be a promising new fluoroquinolone with acceptable susceptibility testing methods for routine clinical laboratory use.

Anti-streptococcal activity of SB-265805 (LB20304), a novel fluoronaphthyridone, compared with five other compounds, including quality control guidelines.

SB-265805 (formerly LB20304) is a novel C-7 pyrrolidine-substituted naphthyridone that has a broad spectrum of activity, especially against Gram-positive cocci. SB-265805 activity was compared with ciprofloxacin, grepafloxacin, moxifloxacin, sparfloxacin, and penicillin against 599 Streptococcus spp. isolated recently from more than 30 medical centers in North and South America. These included 70 isolates with decreased susceptibility to recently released fluoroquinolones (levofloxacin MIC, > or = 4 micrograms/mL). All strains were tested by reference microdilution methods in lysed horse blood-supplemented Mueller-Hinton broth. Sixteen percent of 148 beta-haemolytic streptococci (strains of gr. B and C) were not susceptible to penicillin, whereas 38% and 42% of viridans group streptococci and Streptococcus pneumoniae were resistant to penicillin, respectively. SB-265805 potency against 301 pneumococci (MIC90, 0.06 microgram/mL) was fourfold more active than moxifloxacin and was > or = eightfold more potent than other quinolones. Against beta-haemolytic streptococci, SB-265805 and moxifloxacin were the most active (MIC90, 0.06 and 0.25 microgram/mL, respectively), whereas sparfloxacin, grepafloxacin, and ciprofloxacin (MIC90, 0.5-1 microgram/mL) were less potent. SB-265805 MICs versus viridans group streptococci (MIC90, 0.12 microgram/mL) were fourfold lower than sparfloxacin or grepafloxacin, and twofold more active than moxifloxacin. A nine-laboratory quality control (QC) protocol conforming to NCCLS M23-T3 guidelines demonstrated a modal SB-265805 MIC of 0.016 microgram/mL for S. pneumoniae ATCC 49619 (proposed QC range, 0.008 to 0.03 microgram/mL). The SB-265805 disk (5-microgram) QC range was 28-34 mm (97.3% of qualifying results). In general, SB-265805 in vitro activity against Streptococcus species was superior to sparfloxacin, grepafloxacin, and moxifloxacin and markedly greater than ciprofloxacin. This degree of antimicrobial potency warrants further investigation of this newer drug for its potential human clinical application against streptococcal infections.

Antimicrobial activity of SCH27899 (Ziracin), a novel everninomicin derivative, tested against Streptococcus spp.: disk diffusion/etest method evaluations and quality control guidelines. The Quality Control Study Group.

To combat the increasing rates of penicillin resistance among pneumococci and viridans group streptococci, new Gram-positive active agents are needed to avoid the overuse of vancomycin. SCH27899 is an everninomicin derivative with strong activity against glycopeptide-resistant enterococci, oxacillin-resistant staphylococci, and penicillin-resistant streptococci. This study tests the in vitro activity of SCH27899 against 304 strains of streptococci and evaluates the quality of the agar dilution, broth microdilution, disk diffusion, and Etest methods for this antimicrobial agent. Quality-control (QC) ranges for SCH27899 are also proposed. SCH27899 broth microdilution MICs among the penicillin-susceptible and -resistant streptococci tested ranged from < or = 0.008-0.5 microgram/mL. Organism groups with their respective MIC90s were as follows: Streptococcus pneumoniae (100 strains) and beta-haemolytic streptococci (70 strains), 0.12 microgram/mL; Streptococcus bovis (10 strains), 0.25 microgram/mL; and viridans group streptococci (124 strains), 0.5 microgram/mL. Etest SCH27899 MICs correlated well with broth microdilution MICs (92% +/- one log2 dilution, 98% +/- two log2 dilutions). Agar dilution SCH27899 MICs correlated well with broth microdilution MICs, but a shift toward slightly higher agar dilution MICs was attributed to difficulties in reading trailing endpoints with this method. Three concentrations (2.5, 5, and 10 micrograms) of SCH27899 were used for the disk diffusion method with small inhibition zone diameters (range, 11 to 19 mm) and limited variation between diameters (+/- 2 mm) as a result, both products of this compound's high molecular weight and poor diffusion through agar mediums. Proposed control ranges for SCH27899 when testing S. pneumoniae ATCC 49619 from a nine-center (30 tests per center) quality-control trial are < or = 0.016 to 0.032 microgram/mL for Etest, and 0.008 to 0.032 microgram/mL for broth microdilution tests from an earlier study. Because of the limited diffusion ability and bacteriostatic nature of SCH27899, MICs should be read at 80% of inhibition with agar in vitro systems (Etest, agar dilution), and the disk diffusion method is not recommended.

Development of in vitro susceptibility testing methods for gemifloxacin (formerly LB20304a or SB-265805), an investigational fluoronaphthyridone.

Potent investigational fluoroquinolones require convenient, but accurate, diagnostic tests for initially applied clinical trials. For this purpose, gemifloxacin (formerly SB-265805, LB20304a) was tested by the reference dilution tests and standardized disk diffusion methods of the National Committee for Clinical Laboratory Standards (NCCLS) to establish interpretive criteria. For rapid-growing pathogens, 986 organisms were tested by broth microdilution MIC, and 5- and 10-microgram disk diffusion tests. Correlation (r) between 5- and 10-microgram disk zone diameters was 0.99 (y = -0.12 to 0.99x) and the preferred 5-microgram disk zone/MIC scattergram produced a regression of y = 14.8 to 0.41x (r = 0.93). At potential pharmacodynamics (Cmax = 1.3 micrograms/mL for 320 mg dose) validated breakpoints of < or = 0.5 microgram/mL for susceptible and > or = 2 micrograms/mL for resistant, correlate zones of > or = 17 mm and < or = 13 mm produced rare serious interpretive errors (0.1%) and 96.7% absolute categorical agreement. For 304 Streptococcus pneumoniae and 305 strains of other streptococci, the same breakpoints produced 100 and 99.1% categorical accuracy even when testing levofloxacin-resistant (MIC, > or = 4 micrograms/mL) strains. Interpretive breakpoints were proposed for Hemophilus influenzae (300 strains tested), with complete correlation between tests. Etest (AB BIODISK, Solna, Sweden) was compared in all experiments with the fastidious species and showed a trend toward higher values (twofold). Gemifloxacin in vitro susceptibility test methods seem to be accurate and with very acceptable intermethod agreement, supported by previously reported functional quality control guidelines.

In vitro susceptibility testing and quality control parameters for sarafloxacin (A-56620): a fluoroquinolone used for treatment and control of colibacillosis in poultry. Quality Control Study Group.

Sarafloxacin (formerly A-56620) is a fluoroquinolone recently introduced into veterinary practice for the therapy of colibacillosis and other indicated infections. Sarafloxacin was noted to be very active and comparable to ciprofloxacin and enrofloxacin for inhibiting 823 strains from a wide variety of species at < or = 1 or < or = 2 micrograms/mL. In vitro susceptibility tests for sarafloxacin using National Committee for Clinical Laboratory Standards (NCCLS) methods were also studied and interpretive criteria for Escherichia coli-associated colibacillosis isolates were proposed: susceptible at < or = 0.06 microgram/mL (> or = 25 mm) and resistant at > or = 0.25 microgram/mL (< or = 21 mm). Sarafloxacin agar dilution MIC results were approximately one log2 dilution higher than broth microdilution endpoints. The interpretive criteria demonstrated a low error rate of 5.9%, with a very major rate of only 0.5% (correlation coefficient between methods = 0.94). Quality control trials in six laboratories established MIC and zone diameter (5-microgram disk) limits for the NCCLS recommended strains: for the broth microdilution test, E. coli ATCC 25922 = 0.008 to 0.03 microgram/mL, Pseudomonas aeruginosa ATCC 27853 = 0.12 to 1 microgram/mL, Enterococcus faecalis ATCC 29212 = 0.5 to 2 micrograms/mL, and Staphylococcus aureus ATCC 29213 = 0.06 to 0.25 microgram/mL; and for the disk diffusion test, E. coli ATCC 25922 = 30 to 36 mm, S. aureus ATCC 25923 = 25 to 30 mm, and P. aeruginosa ATCC 27853 = 23 to 29 mm. These criteria for in vitro tests with sarafloxacin should enable the longitudinal monitoring of its activity against the indicated pathogens and allow detection of emerging resistant populations that may necessitate altered dosing regimens.

Antimicrobial activity and spectrum investigation of eight broad-spectrum beta-lactam drugs: a 1997 surveillance trial in 102 medical centers in the United States. Cefepime Study Group.

Because antimicrobial agents become less effective after the emergence of resistance mechanisms in clinically prevalent pathogens, physicians must utilize local, regional, and national antimicrobial susceptibility surveillance data to assist in choices of appropriate agents. An investigation of the spectrum and potency of eight broad-spectrum beta-lactam drugs (cefepime, cefotaxime, ceftazidime, ceftriaxone, imipenem, piperacillin with or without tazobactam, and ticarcillin/clavulanic acid) was performed using a common protocol and method (Etest; AB BIODISK, Solna, Sweden) in 102 clinical microbiology laboratories in the United States. A total of 9777 strains of Gram-negative bacilli were tested from late 1996 through April 1997. Quality assurance measures using three control strains observed quality control failures in 13 laboratories (usually ticarcillin/clavulanic acid or piperacillin), but only 2% of results required deletion. A total of 33.4% of Enterobacter spp. (1977 strains) were either resistant or intermediately susceptible to ceftazidime. Only imipenem (99.6% susceptible) and cefepime (99.1%) remained highly active against strains of Enterobacter, as well as Citrobacter freundii, indole-positive Proteae, and Serratia spp. Ceftazidime-resistant Escherichia coli and Klebsiella pneumoniae were detected at rates of 10.3% and 23.8%, respectively. Although these were participant-selected strains, only imipenem and cefepime had broad-spectrum coverage (> or = 97.1%) against these extended-spectrum beta-lactamase phenotypes. A dominant number of these extended-spectrum beta-lactamase phenotypes were reported from medical centers in the Northeast, but a nationwide distribution was observed. Among the nonenteric Gram-negative bacilli (4057 strains), the rank order of susceptibility (percent inhibited at published breakpoint concentrations) was: imipenem (86.1%) > piperacillin/tazobactam (80.1%) > cefepime (77.1%) > ceftazidime = piperacillin (74.9%) > ticarcillin/clavulanic acid (61.6%) > cefotaxime (18.2%) > ceftriaxone (12.9%). The cephalosporins, cefepime and ceftazidime, had rates of resistance for the 3005 Pseudomonas aeruginosa isolates of 10.1% and 14.4%, respectively. For all Gram-negative strains tested, only two contemporary beta-lactam antimicrobials exhibited > 90% inhibition of strains, imipenem at 93.6% and cefepime at 90.2%. These drugs were superior to the other tested compounds (48.8-84.3%). Ticarcillin/clavulanic acid had the narrowest spectrum of activity (48.8% of isolates susceptible). These results indicate that carbapenems and a new fourth-generation cephalosporin, cefepime, possess usable in vitro potencies against current clinical strains of Gram-negative bacilli, many of which harbored resistance to other antimicrobial agents.

The prevalence of fluoroquinolone resistance among clinically significant respiratory tract isolates of Streptococcus pneumoniae in the United States and Canada--1997 results from the SENTRY Antimicrobial Surveillance Program.

As part of the SENTRY antimicrobial resistance surveillance program, a total of 1100 clinically significant respiratory tract isolates of Streptococcus pneumoniae were tested for susceptibility to six fluoroquinolone antimicrobial agents: ciprofloxacin, levofloxacin, gatifloxacin, grepafloxacin, sparfloxacin, and trovafloxacin. Isolates were obtained during the 5-month period, February to June, 1997 from 27 United States medical center laboratories and seven laboratories in Canadian health care institutions. All testing was performed in a single center. Of 1100 test strains, 3 (0.3%), all from different U.S. centers, were fluoroquinolone resistant. Among the remaining 1097 fluoroquinolone-susceptible isolates, the rank order of activity among the six agents tested in this study was grepafloxacin (modal MIC = 0.25 microgram/mL) = trovafloxacin (modal MIC = 0.25 microgram/mL) = sparfloxacin (0.25 microgram/mL) > gatifloxacin (0.5 microgram/mL) > levofloxacin (1 microgram/mL) = ciprofloxacin (1 microgram/mL). Fluoroquinolone resistance is currently uncommon among respiratory tract isolates of S. pneumoniae in North America, but there exist clear differences between the in vitro activities of different fluoroquinolones for this organism.

Nosocomial enterococcal blood stream infections in the SCOPE Program: antimicrobial resistance, species occurrence, molecular testing results, and laboratory testing accuracy. SCOPE Hospital Study Group.

Characteristics of nosocomial enterococcal blood stream infection (NEBSI) isolates obtained from patients at 41 U.S. hospitals participating in the SCOPE Program were studied. Isolates from 480 episodes of NEBSI were characterized according to species and antimicrobial susceptibility profile. Selected isolates were also identified to species and vancomycin resistance genotype using polymerase chain reaction based methods. Polymerase chain reaction genotyping and ribotyping were used as genetic markers for molecular epidemiologic typing. Enterococci were the third most common cause of nosocomial blood stream infection in this study, accounting for 11.7% of all isolates reported. Enterococcus faecalis was the most common species (59.6%), followed by E. faecium (19.4%). Species identification errors involving E. faecium, E. durans, E. avium, and E. raffinosus were observed. Vancomycin resistance was observed in 36.4% of all participating medical centers and varied from 11.1% of medical centers in the Northwest to 60.9% of medical centers in the Southwest. Vancomycin-resistant enterococci accounted for 20.6% of NEBSI in the Northeast, 11.4% in the Southeast, 11.1% in the Southwest, and 9.5% in the Northwest regions. VanA genotypes predominated in the Northeast and Southwest, whereas vanA and vanB genotypes were equally prevalent in the Northwest and Southeast. Molecular typing studies identified strains that were unique to individual hospitals as well as strains that were prevalent in several different hospitals. NEBSI with vancomycin-resistant enterococci continues to escalate among hospitalized patients in all geographic areas of the USA.

In vitro antimicrobial activity of RU-59863, a C-7 catechol substituted cephalosporin.

The in vitro activity of RU-59863, a so-called "fifth generation" catechol cephalosporin, was evaluated against 606 bacterial isolates and compared with the activities of cefotaxime, ceftazidime, cefepime, and cefpirome. RU-59863 demonstrated a broad spectrum of inhibition and superior overall activity than comparators when tested against Enterobacteriaciae (MIC90s, 0.015 to 2 micrograms/ml), Pseudomonas aeruginosa (MIC90, 0.5 microgram/ml), Stenotrophomonas maltophilia (MIC90, 0.25 microgram/ml), Acinetobacter ssp. (MIC90, 4 micrograms/ml), and oxacillin-susceptible Staphylococcus ssp. (MIC90s, 0.5 to 8 micrograms/ml). Potent RU-59863 activity was also observed against beta-haemolytic and viridans gr. streptococci (MIC90s, 0.12-0.5 microgram/ml), Streptococcus pneumoniae (MIC90s, 0.03 to 0.5 microgram/ml), Haemophilus influenzae (MIC90, 0.06 microgram/ml), and Neisseria gonorrhoeae (MIC90, 0.06 micrograms/ml). RU-59863 demonstrated marginal potency against Enterococcus faecalis (MICs 2 to 16 micrograms/ml) and was inactive against Enterococcus faecium (MIC90, > 128 micrograms/ml). Oxacillin-resistant staphylococci were not inhibited by RU-59863 (MIC90s, 32 to 128 micrograms/ml). Among the cephalosporins tested, RU-59863 performed best versus ceftazidime-resistant Bush group 1 isolates and strains producing extended spectrum beta-lactamases. RU-59863 was also effective against many fluoroquinolone-, aminoglycoside-, and imipenem-resistant isolates. RU-59863 seems to be a significant advance in cephalosporin chemistry and activity, especially against Gram-negative pathogens resistant to current beta-lactam therapeutic agents. Further studies of human pharmacokinetics and against clinical infections are encouraged.