Biomedical subjects

R N Jones

Publications and source records attributed to R N Jones.

At least 199 records · Page 11Linked to original sources

PubMed1999

Bacterial pathogens isolated from patients with skin and soft tissue infections: frequency of occurrence and antimicrobial susceptibility patterns from the SENTRY Antimicrobial Surveillance Program (United States and Canada, 1997). SENTRY Study Group (North America).

As part of the SENTRY Antimicrobial Surveillance Program, 1562 bacterial isolates were recovered from hospitalized patients with skin and soft tissue infections (SSTIs) in 30 United States (U.S.) and 8 Canadian medical centers between October and December, 1997. The overall rank order of recovery of the six most common pathogens was Staphylococcus aureus (42.6%) > Pseudomonas aeruginosa (11.3%) > Enterococcus spp. (8.1%) > Escherichia coli (7.2%) > Enterobacter spp. (5.2%) > beta-hemolytic streptocci (5.1%). With one exception, essentially the same order was observed in both the U.S. and Canada. The single exception was the Enterococcus group, which were the third most common isolate in the U.S. (9.6%), but the seventh most common isolate in Canada (3.7). Of note, 24.0% of S. aureus isolates were oxacillin resistant; vancomycin was uniformly active. Vancomycin resistance among Enterococcus spp. (16.5%) was observed only in the U.S. Several antimicrobial agents remained broadly active for SSTI isolates of P. aeruginosa, including meropenem, amikacin, tobramycin, and piperacillin with or without tazobactam. Imipenem resistance (MICs, > or = 8 micrograms/mL) was observed in 11.9% of isolates of P. aeruginosa and ceftazidime, and cefepime had equivalent activity (85.2% and 85.8% susceptible, respectively). Numerous beta-lactams, aminoglycosides and fluoroquinolones were broadly active against E. coli SSTI isolates (i.e. < 5% resistance). Extended-spectrum beta-lactamase production was uncommon both with E. coli and Klebsiella spp. in both nations. Cefepime, imipenem, and meropenem; the aminoglycosides; and fluoroquinolones were conspicuously more active against Enterobacter spp. than other agents tested. High-level, stably derepressed Amp C beta-lactamase production was commonly observed in this group (26.8%), but cefepime generally retained activity against these ceftazidime-resistant organisms. The results of this study serve to define the most common bacterial causes of SSTIs in North America, elucidate patterns of antimicrobial resistance and can be used as a basis for making initial empiric antimicrobial management decisions in hospitalized patients with such infections.

Anti-Bacterial Agents↗

PubMed1999

Determination of the antimicrobial activity of 29 clinically important compounds tested against fastidious HACEK group organisms.

HACEK group organisms are very fastidious organisms (Haemophilus spp., Actinobacillus actinomycetemcomitans, Cardiobacterium hominus, Eikenella corrodens, Kingella spp.) that can produce serious invasive infections such as endocarditis. Problems with susceptibility testing methods and their rarity of isolation limit available information of therapeutic choices, particularly among newer antimicrobial agents. Forty-two HACEK strains were tested by the Etest (AB BIODISK, Solna, Sweden) method against 29 antimicrobial agents. Nearly all compounds exhibited activity with best potency observed among the tested beta-lactamase inhibitor combinations, "third- or fourth-generation" cephems, meropenem, fluoroquinolones, and rifampin. Numerous therapeutic options appear possible for initial parenteral treatment followed by oral "step-down" or switch therapy. Each case of HACEK infection therapy should be guided by accurate susceptibility tests, for which the Etest seems preferred for these fastidious species.

Anti-Bacterial Agents↗

PubMed1999

Antimicrobial activity of gatifloxacin compared to seven other compounds tested against gram-positive organisms isolated at 10 cancer-treatment centers.

Gram-positive bacterial pathogens are important causes of disease in cancer patients and are becoming increasingly resistant to available antimicrobial agents. We examined the in vitro activity of gatifloxacin, a new fluoroquinolone, compared with other quinolones, ceftazidime, and traditional Gram-positive-active agents tested against pathogens isolated from patients at 10 cancer treatment hospitals in the United States. A total of 1,128 Gram-positive isolates were tested by the E-test method (AB BIODISK, Solna, Sweden) with results validated by concurrent quality control strain analysis. Gatifloxacin was more potent than either ciprofloxacin or levofloxacin against all Gram-positive species. Vancomycin was the most active agent tested against all species except Bacillus spp., which were more susceptible to the fluoroquinolones. When tested against these Gram-positive pathogens from patients with cancer, the spectrum of gatifloxacin was also greater than that of levofloxacin and ciprofloxacin. Gatifloxacin may have a role as part of prophylactic or therapeutic antimicrobial regimens for selected cancer patients with Gram-positive infections.

Anti-Bacterial Agents↗

PubMed1999

Phenotypic and genotypic characterizations of Chinese strains of Escherichia coli producing extended-spectrum beta-lactamases.

Twenty-three multi-resistant strains of Escherichia coli were isolated at a single hospital in Beijing, China between January 1997 and May 1998. All isolates produced extended spectrum beta-lactamases (ESBLs) as detected by the double disk synergy test and the Etest ESBL strip (AB BIODISK, Solna Sweden). Additional antimicrobial susceptibility testing showed that most isolates were resistant to gentamicin, tobramycin, tetracycline, trimethoprim/sulfamethoxazole, ciprofloxacin, and cefepime. All isolates remained susceptible to imipenem with MICs of < or = 0.5 microgram/ml. The isolates each produced several beta-lactamases (range 1-4 enzymes/strain) with pI values ranging from 5.2-8.4. Molecular epidemiologic typing revealed four ribotypes and eight pulsed field gel electrophoresis (PFGE) patterns with subgroups among the 23 isolates. Clusters of isolates with the same DNA type were observed as follows (ribotype/PFGE): Wards A (242-5/2, and 242-5/3a), B (242-5/4), and C (880-1/1a). Moreover, similar molecular types were observed in patients from two or more different wards. Further use of isoelectric focusing results and co-resistance patterns produced evidence of potential nosocomial dissemination of strains in only two instances (two identical strains on one ward and two identical strains on different wards). There were also strong similarities in beta-lactamase pIs and co-resistances among many of the strains throughout this medical center. These data document the wide genetic diversity among E. coli producing ESBLs, and a potential for nosocomial spread of these highly resistant organisms requiring increasingly more sophisticated molecular-based techniques and local interventions.

Anti-Bacterial Agents↗

PubMed1999

Evaluation of the in vitro activity of six broad-spectrum beta-lactam antimicrobial agents tested against over 2,000 clinical isolates from 22 medical centers in Japan. Japan Antimicrobial Resistance Study Group.

Numerous broad-spectrum beta-lactam antimicrobial agents have been introduced into medical practice since 1985. Although several of these compounds have advanced, infectious disease therapy resistances to them has also emerged world-wide. In 1997, a Japanese 22 medical center investigation was initiated to assess the continued utility of these agents (oxacillin or piperacillin, ceftazidime, cefepime, cefpirome, cefoperazone/sulbactam [C/S], imipenem). The participating medical centers represented a wide geographic distribution, and a common protocol and reagents were applied. Three control strains and a set of challenge organisms were provided to participant centers. Etest (AB BIODISK, Solna, Sweden) strips were used in concurrent tests of these organisms and a qualitative determination of participant skills in the identification of resistant and susceptible phenotypes was established. The quantitative controls demonstrated 97.7-99.2% of MIC values within established QC limits, and the qualitative (susceptibility category) controls documented a 97.3% agreement of participant results with that of reference values (1,320 total results). Only 0.2% of values were false-susceptible errors. After the participant quality was assured, a total of 2,015 clinical strains were tested (10 strains from 10 different organism groups including methicillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci [CoNS], Escherichia coli, Klebsiella spp., Citrobacter freundii, Enterobacter spp., indole-positive Proteae, Serratia spp., Acinetobacter spp., and Pseudomonas aeruginosa). The staphylococci were uniformly susceptible to all drugs tested except ceftazidime (MIC90, 24 micrograms/ml) that had a potency six- to 12-fold less than either cefepime or cefpirome. Only 3.7 and 45.1% of S. aureus and CoNS were susceptible to ceftazidime, respectively. Among E. coli and Klebsiella spp. the rank order of antimicrobial spectrum was imipenem = "fourth-generation" cephalosporins > ceftazidime > C/S > piperacillin. Possible extended spectrum beta-lactamase phenotypes were identified in 2.9-8.6% of these isolates. Isolates of C. freundii, Enterobacter spp., Proteae, and Serratia spp. that were resistant to ceftazidime and piperacillin remained susceptible to imipenem (0.0-4.5% resistance) and cefepime (0.0-5.0%). Acinetobacters were inhibited best by C/S (99.5% susceptible) and least susceptible to piperacillin (MIC90, > 256 micrograms/ml; 21.7% susceptible) activity. P. aeruginosa isolates were most susceptible to cefepime (83.6%) and this zwitterionic cephalosporin also had the lowest level of resistance (9.1% of MICs at > or = 32 micrograms/ml). Several multi-resistant organisms were identified in participant medical centers including S. marcescens strains resistant to cefepime, imipenem, or both observed in six hospitals. Clonal spread was documented in two medical centers; one hospital having two distinct epidemic clusters. Also a multi-resistant E. cloacae was found in two patients in the same hospital. Evaluations of carbapenem resistance in four species discovered only two strains (in same hospital) among 40 P. aeruginosa isolates (5.0%) with a metallo-enzyme, with nearly all of the remaining strains inhibited by an Ambler Class C enzyme inhibitor (BRL42715) indicating a hyperproduction of a chromosomal cephalosporinase. These results indicate that most newer beta-lactams remain widely useable in medical centers in Japan, but emerging often clonal, resistances have occurred. The overall rank order of antimicrobial spectrum against all ten tested bacterial groups favors the "fourth-generation" cephalosporin, cefepime (96.4% susceptible) as an equal to imipenem (95.9%) > C/S (90.9%) = cefpirome (90.0%) > ceftazidime (75.1%) = penicillins, either oxacillin or piperacillin (76.4%).

Anti-Bacterial Agents↗

PubMed1999

Comparative activity of clinafloxacin and nine other compounds tested against 2000 contemporary clinical isolates from patients in United States hospitals.

The in vitro activity of clinafloxacin (formerly CI-960, AM-1091, PD-127391) was compared with other fluoroquinolones, cephalosporins, gentamicin, vancomycin, imipenem, piperacillin/tazobactam, clindamycin, and metronidazole against 2000 recent clinical strains from a large number of hospitals in the United States. Overall, clinafloxacin was the most active compound tested. Against Pseudomonas aeruginosa, clinafloxacin and ciprofloxacin demonstrated comparable activity (88% and 80% susceptible, respectively), and were four- to 16-fold more potent than levofloxacin (MIC90, 16 micrograms/ml) or trovafloxacin (MIC90, 32 micrograms/ml). Among anaerobic bacteria, clinafloxacin (MIC50s, 0.25-0.5 microgram/ml) and trovafloxacin (MIC50s, 0.5-2.0 micrograms/ml) were the most active quinolones, whereas metronidazole, imipenem and piperacillin/tazobactam were the most potent comparators. Clinafloxacin demonstrated sustained activity when compared to several available peer drugs against contemporary clinical isolates. The clinafloxacin spectrum against the 15 important pathogens monitored ranged from nil or 4.0% (vancomycin-resistant enterococci) to 100.0% (four different species) susceptible with an average percent susceptibility of 94.0%. This degree of potency and spectrum for clinafloxacin provides a wide potential for use against many species with established resistance to other anti-microbial classes.

Anti-Infective Agents↗

PubMed1999

Practical approach to the identification of clinically relevant Enterococcus species.

Enterococci have become important nosocomial pathogens, with Enterococcus faecalis and then Enterococcus faecium predominating. Because of the emergence of glycopeptide (vancomycin and teicoplanin) resistance in enterococci, laboratories have been required to screen for resistant strains and to identify them to the species level. This has resulted in the need for accurate identification of species less commonly associated with clinical infections, such as Enterococcus casseliflavus and Enterococcus gallinarum, which are inherently resistant to the glycopeptides. Studies evaluating commonly used commercial identification systems, have found error rates for enterococcal species identification of 2-21% for E. faecalis, 5-9% for E. faecium, and 14-79% for other species. Reporting errors may have adverse effects on the management of clinical infections, as well as in the control of multidrug-resistant strain outbreaks. The purpose of this document is to present a simplified approach to the identification of Enterococcus species that uses a combination of rapid, readily available, and inexpensive tests.

Anti-Bacterial Agents↗

PubMed1999

Antimicrobial activity of gatifloxacin (AM-1155, CG5501), and four other fluoroquinolones tested against 2,284 recent clinical strains of Streptococcus pneumoniae from Europe, Latin America, Canada, and the United States. The SENTRY Antimicrobial Surveillance Group (Americas and Europe).

The newer fluoroquinolones generally have greater potency against Gram-positive cocci including Streptococcus pneumoniae. In this study, we report the activity of gatifloxacin (formerly AM-1155 or CG5501) compared with penicillin, erythromycin, and four other peer drugs, tested against 2284 strains isolated in North America (Canada and United States), Latin America (six nations), and Europe in 1997. Reference broth microdilution methods were used and results were interpreted by consensus standards. Gatifloxacin demonstrated uniform potency against pneumococci across all monitored geographic areas (MIC90, 0.5 microgram/mL; > or = 99.6% of strains inhibited at < or = 1 microgram/mL). This activity was comparable to trovafloxacin (MIC90, 0.5 microgram/mL) and sparfloxacin (MIC90, 0.5 microgram/mL) and two- to four-fold greater than that of ciprofloxacin or levofloxacin. The most resistant strains to the fluoroquinolones had mutations in both par C (Ser 79-->Phe) and gyr A (Ser83-->Lys or Phe). Penicillin resistance (MIC, > or = 0.12 microgram/mL) rates varied from 27.6% in Europe to 55.7% in Latin America. Macrolide resistance was greatest in Europe and the United States. Gatifloxacin appears to be a promising new fluoroquinolone for clinical use in respiratory tract infections commonly caused by S. pneumoniae.

Anti-Infective Agents↗

PubMed1999

International surveillance of blood stream infections due to Candida species in the European SENTRY Program: species distribution and antifungal susceptibility including the investigational triazole and echinocandin agents. SENTRY Participant Group (Europe).

The SENTRY Antimicrobial Surveillance Program, an international study of blood stream infections (BSIs), detected 170 episodes of candidemia in 20 European medical centers (13 nations) between January and December, 1997. Twenty-three percent of the candidal BSI occurred in patients hospitalized in an intensive care unit, 21% in patients in an internal medicine service, 13% in patients in a surgical service, and 9% in patients in an oncology service. Overall, 53% of the BSI were attributable to Candida albicans followed in prevalence by C. parapsilosis (21%), C. glabrata (12%), C. tropicalis (6%), C. famata (2%), C. krusei (1%), and C. inconspicua (1%). As observed previously in Canada and Latin America, C. parapsilosis and not C. glabrata, was the most common non-albicans species causing yeast BSI in Europe. The proportion of these candidemias attributable to C. albicans varied widely from 0-100% among the 20 European centers. Among the different species of Candida, resistance to fluconazole (MIC, > or = 64 micrograms/mL) and itraconazole (MIC, > or = 1.0 microgram/mL) was observed with C. glabrata and C. krusei and was observed more rarely among other species (e.g., C. inconspicua). Isolates of C. albicans, C. parapsilosis, C. tropicalis, and C. guilliermondii were all highly susceptible to both fluconazole and itraconazole. Furthermore, the investigational triazoles (BMS-207147, Sch 56592, and voriconazole) and an echinocandin (MK-0991) all demonstrated potent in vitro activity (MIC90s, 0.5, 0.5, 1.0, and 2.0 micrograms/mL, respectively) against these isolates. Continued surveillance at an international level will be important to monitor trends in species distribution and antifungal susceptibility among invasive strains of Candida.

Antifungal Agents↗

PubMed1999

Colony morphology of Candida spp. as a guide to species identification.

The presence of colony projections, often referred to as "feet," have typically been considered a characteristic of Candida albicans. In the current study that examined the colony morphology of numerous different species of Candida, several clinical isolates of Candida tropicalis and Candida krusei were also noted to produce "feet." The medium and growth conditions under which colony projections were produced by these species were characterized.

Candida↗

PubMed1999

Multicenter evaluation of the antimicrobial activity for seven broad-spectrum beta-lactams in Turkey using the Etest method. Turkish Antimicrobial Resistance Study Group.

From March through July 1997, a nine laboratory surveillance project was initiated in Turkey to monitor the potency and spectrum of seven broad-spectrum antimicrobial agents (cefepime, ceftazidime, cefotaxime, imipenem, aztreonam, cefoperazone/sulbactam, and ticarcillin/clavulanate) tested against approximately 100 organisms (average 82; range 70 to 95 isolates) per participant center (736 strains). Eleven groups of organisms were tested by the Etest method (AB BIODISK, Solna, Sweden) with results validated by concurrent quality control strain analysis. Results from all centers were tabulated and 91.1% of quality assurance tests were within ranges recommended by the National Committee for Clinical Laboratory Standards. Among the seven beta-lactam-class drugs tested, imipenem and cefepime were the most active beta-lactams tested against all isolates. Overall, the rank order of susceptibility of the seven agents was imipenem > cefepime > cefoperazone/sulbactam > ceftazidime > cefotaxime > aztreonam > ticarcillin/clavulanate. Both cefepime and imipenem were active against ceftazidime-resistant strains of Enterobacteriaceae as well as against Streptococcus spp. and oxacillin-susceptible Staphylococcus aureus. Resistance phenotypes consistent with extended spectrum beta-lactamases were documented among Escherichia coli and Klebsiella spp., and profiles consistent with stably derepressed Bush-Jacoby-Mederios group 1 (Amp C) cephalosporinases were common among Enterobacter spp., Citrobacter spp., and Serratia spp. These data should be used to guide empiric therapy with beta-lactams in Turkey, and additionally will provide a reference statistical baseline to which future national studies of drugs in this class can be compared.

Anti-Bacterial Agents↗

PubMed1999

Evaluation of the in vitro antimicrobial activity of cefepime compared to other broad-spectrum beta-lactams tested against recent clinical isolates from 10 Chinese hospitals. Chinese Antimicrobial Resistance Study Group.

A surveillance study was initiated in China in 1998 in which 10 medical centers participated. The susceptibility profiles of 996 commonly occurring pathogens belonging to 10 different species groups were tested by the Etest (AB BIODISK, Solna, Sweden) against six broad-spectrum beta-lactam antimicrobial agents (cefepime, ceftazidime, ceftriaxone, imipenem, cefoperazone/sulbactam and piperacillin or oxacillin). Quality control was closely monitored and cefepime- and/or imipenem-resistant Enterobacteriaceae were referred to the reference laboratory (University of Iowa College of Medicine, Iowa City, IA) for confirmation. The isolates of Citrobacter spp. and Enterobacter spp. were generally inhibited by imipenem (100% susceptible) and cefepime (89-94%), but were more resistant to the other drugs tested (< or = 74% susceptible). The indole-positive Proteus spp. and Serratia spp. isolates were > 94% susceptible to all tested beta-lactams except piperacillin. Organisms capable of producing extended spectrum beta-lactamases (ESBLs), which included Klebsiella spp. and Escherichia coli, were most susceptible to imipenem (100%) and cefepime (> 90%). Among the non-enteric Gram-negative bacilli, all drugs were marginally active against Pseudomonas aeruginosa (MIC90s, 32-> 256 ug/mL) and the Acinetobacter spp. were rather resistant to all the compounds, except imipenem (96% susceptible). All strains of Staphylococcus spp. were susceptible to the tested antimicrobials except for ceftazidime, which had a low potency (MIC90, 12-16 micrograms/mL) against Chinese isolates with MICs that fell into the intermediate category. Cefepime, the fourth-generation cephalosporin, showed a very broad spectrum of activity against Gram-negative pathogens as well as oxacillin-susceptible Staphylococcus spp. that was comparable with imipenem (widest spectrum) and superior to the other tested beta-lactams overall. Continued monitoring of clinical strains in China seems necessary to guide chemotherapy.

Anti-Bacterial Agents↗

PubMed1999

Multicenter evaluation of the antimicrobial activity for six broad-spectrum beta-lactams in Venezuela: comparison of data from 1997 and 1998 using the Etest method. Venezuelan Antimicrobial Resistance Study Group.

The minimum inhibitory concentrations of six broad-spectrum beta-lactam antimicrobial agents were determined in 1998 by use of the Etest versus a total of 502 bacteria in seven Venezuelan hospital laboratories. These data were compared with results of a similar study performed in 1997. The organisms tested included 309 recent clinical isolates of Enterobacteriaceae, 70 Pseudomonas aeruginosa, 54 Acinetobacter species, and 69 oxacillin-susceptible Staphylococcus aureus. Extended spectrum beta-lactamase production was noted among 30% of Klebsiella pneumoniae isolates. Hyperproduction of Amp C cephalosporinase producing resistance to ceftazidime and cefotaxime was observed with 10 to 37% of isolates of Enterobacter spp., Serratia spp., and Citrobacter freundii. The overall rank order of activity of the six beta-lactams tested in this study against all clinical isolates was imipenem (96.6% susceptible) > cefepime (90.4%) > piperacillin/tazobactam (85.7%) > ceftazidime (73.5%) > cefotaxime (70.5%) > piperacillin (55.0%). These findings were very similar to those reported for 1997.

Anti-Bacterial Agents↗

PubMed1999

Multicenter evaluation of antimicrobial resistance to six broad-spectrum beta-lactams in Colombia: comparison of data from 1997 and 1998 using the Etest method. The Colombian Antimicrobial Resistance Study Group.

The minimum inhibitory concentrations of six broad-spectrum beta-lactam antimicrobial agents were determined in 1998 by use of the Etest versus a total of 823 bacteria in 11 Colombian hospital laboratories. These data were compared with results of a similar study conducted in 1997. The organisms tested included 532 recent clinical isolates of Enterobacteriaceae, 108 Pseudomonas aeruginosa, 94 Acinetobacter species, and 89 oxacillin-susceptible Staphylococcus aureus. Extended-spectrum beta-lactamase production was noted among 27.8 to 33.9% of Escherichia coli isolates and 41.7 to 46.7% of Klebsiella spp. isolates. Hyperproduction of Amp C cephalosporinases was observed with 10.5 to 31.4% of isolates of Enterobacter spp., Serratia spp., and Citrobacter spp. An increase in resistance to all of the beta-lactams was observed among Enterobacteriaceae, Acinetobacter spp. and P. aeruginosa when 1998 results were compared with those obtained in 1997. The overall rank order of activity of the six beta-lactams tested in 1998 versus all clinical isolates was imipenem (93.2% susceptible) > cefoperazone/sulbactam (84.1%) > cefepime (80.9%) > ceftazidime (70.7%) > aztreonam (65.7%) > cefotaxime (65.6%). In contrast, the rank order of these same agents tested against a similar collection of Colombian isolates in 1997 was imipenem (96.6% susceptible) > cefepime (93.6%) > cefoperazone/sulbactam (90.5%) > cefotaxime (74.9%) > aztreonam (74.3%) > ceftazidime (73.2%).

Colombia↗

PubMed1999

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.

Anti-Infective Agents↗

PubMed1999

Disk diffusion susceptibility test development for the new glycylcycline, GAR-936.

The in vitro activity of GAR-936, a new semisynthetic glycylcycline, was evaluated in comparison with two tetracyclines and the disk diffusion susceptibility test was assessed. Nearly 700 recent clinical isolates were tested by reference broth microdilution and disk diffusion (two disk contents) methods. Among the Enterobacteriaceae, GAR-936 was generally two- to 16-fold more active than other tetracyclines. All enteric bacilli MIC90 results were < or = 4 micrograms/mL; the exception being Proteus mirabilis and indole-positive Proteae (> or = 8 micrograms/mL). GAR-936 demonstrated excellent activity against all Gram-positive cocci with Enterococcus spp. (including vancomycin-resistant isolates) inhibited at 0.25 microgram/mL (GAR-936 MIC90, 0.12 or 0.25 microgram/mL) and the oxacillin-resistant Staphylococcus aureus strains were inhibited at < or = 0.25 microgram/mL. GAR-936 demonstrated good potency against several non-fermentative bacteria, but possessed limited activity against Pseudomonas aeruginosa (MIC50, 8 micrograms/mL). In vitro susceptibility test methods were developed (disk diffusion versus reference MIC results) and tentative breakpoints were proposed. Using susceptibility criteria of either < or = 2 or < or = 4 micrograms/mL, GAR-936 in vitro susceptibility tests demonstrated rare significant serious inter-method discords (< or = 1.2%) and an absolute agreement between test results of 92.3 to 96.2%. These results indicate that GAR-936 has potent in vitro activity against a wide range of clinically important rapidly growing pathogenic bacteria, and that this novel glycylcycline candidate for clinical use should be further developed.

Anti-Bacterial Agents↗

PubMed1999

In vitro evaluation of cefepime and other broad-spectrum beta-lactams for isolates in Malaysia and Singapore medical centers. The Malaysia/Singapore Antimicrobial Resistance Study Group.

The degree of activity of several beta-lactam antimicrobial agents was assessed in Malaysia (four medical centers) and Singapore (two medical centers) tested against 570 clinical isolates. The organisms were tested locally by the Etest (AB BIODISK, Solna, Sweden) method, validated by concurrent use of quality assurance strains (94.1% accurate performance overall). Ten groups of bacteria were tested against cefepime, cefpirome, ceftazidime, ceftriaxone, piperacillin/tazobactam, oxacillin, and imipenem. Among the tested Escherichia coli and Klebsiella spp., the occurrence of extended spectrum beta-lactamase-producing phenotypes was 5.6-7.0% and 36.7-38.0%, respectively. These strains remained most susceptible (97.5-100.0%) to cefepime and imipenem. Ceftazidime-resistant Enterobacter spp. (21.4% resistant), Citrobacter spp. (15.0%), indole-positive Proteus spp. (6.0%), and Serratia spp. (9.7%) were not resistant to cefepime, and only one strain was resistant to imipenem. Imipenem was generally most potent against non-fermentative Gram-negative bacilli such as Acinetobacter spp. and Pseudomonas aeruginosa. All tested beta-lactams were active against the oxacillin-susceptible staphylococci, except ceftazidime (MIC90, 12 micrograms/mL; 63.2-84.8% susceptibility rates). Overall spectrums of activity (rank by % resistance) favored imipenem (3.5%) > cefepime (7.7%) > cefpirome (8.9%) > piperacillin/tazobactam (13.2%) > ceftriaxone (14.7%) > ceftazidime (16.9%). No significant differences in resistance patterns were noted between monitored nations, and these results indicate emerging, elevated rates of resistance versus the studied broad-spectrum beta-lactams in Malaysia and Singapore. Results provide benchmark data for future studies using quantitative methods to determine antimicrobial resistance in these geographic areas.

Acinetobacter↗

PubMed1999

In vitro evaluation of cefepime and other broad-spectrum beta-lactams against bacteria from Indonesian medical centers. The Indonesia Antimicrobial Resistance Study Group.

The in vitro activity of cefepime and six other broad-spectrum beta-lactams (cefpirome, ceftazidime, ceftriaxone, imipenem, piperacillin/tazobactam (4 micrograms/mL fixed concentration), and oxacillin was evaluated against 191 isolates of clinical bacteria from Indonesia. Susceptibility testing was performed using Etest (AB BIODISK, Solna, Sweden) methodology. Isolates from 10 species groups were selected for analysis: Escherichia coli, Klebsiella spp., Enterobacter spp., indole-positive Proteae, Serratia spp., Acinetobacter spp., Pseudomonas aeruginosa, and oxacillin-susceptible staphylococci. The overall rank order of spectrum of activity was (% resistant): imipenem (2.2%) > cefepime (7.3%) > piperacillin/tazobactam > cefpirome > ceftazidime > ceftriaxone (16.2%). The "fourth-generation" cephalosporins, cefepime and cefpirome, displayed greater activity compared with the "third-generation" cephalosporins, ceftazidime, and ceftriaxone, against the 60 E. coli and Klebsiella spp. (30 each) isolates. Phenotypic extended spectrum beta-lactamase occurrence rates among the E. coli and Klebsiella spp. were 23.3 and 33.3%, respectively. Imipenem, cefepime, and cefpirome inhibited 95.7% of the 46 isolates of inducible Amp C cephalosporinase producing Enterobacteriaceae. The majority of the resistance observed to imipenem and cefepime among tested Indoneisian strains was attributable to the nonfermentative Gram-negative bacilli, P. aeruginosa and Acinetobacter spp. These results indicate the presence of beta-lactam resistance in Indonesia and the need for continued antimicrobial surveillance in this nation and region of the world, preferably using accurate quantitative methods.

Anti-Bacterial Agents↗