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PubMed1998

Comparison of in vitro activity of trovafloxacin against gram-positive and gram-negative organisms with quinolones and beta-lactam antimicrobial agents.

The in vitro activity of trovafloxacin against 721 Gram-negative and 498 Gram-positive organisms was determined by the standard microdilution broth method using commercially prepared frozen microtiter plates. The activity of trovafloxacin was compared to ofloxacin, ciprofloxacin, amoxicillin/clavulanate, ampicillin/sulbactam (1:1), piperacillin/tazobactam, ceftriaxone, and imipenem. Trovafloxacin had equal or greater activity compared with the other agents tested against Citrobacter diversus, Enterobacter aerogenes, Enterobacter cloacae, Escherichia coli, Haemophilus influenzae, Stenotrophomonas maltophilia, Serratia marcescens, staphylococci, Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus viridans, group G streptococci, Enterococcus faecalis, and E. faecium. The reliability of the commercially prepared plates for testing the in vitro activity of the quinolones was evaluated by comparing identical isolates also tested by broth microdilution using laboratory prepared plates. The commercially prepared plates generally correlated, within one- to twofold dilutions, with the laboratory prepared plates. There was, however, a large discrepancy obtained when testing Enterobacter agglomerans and E. cloacae, where the commercially prepared plates yielded a significantly higher MIC90 value.

4-Quinolones↗

PubMed1998

Important and emerging beta-lactamase-mediated resistances in hospital-based pathogens: the Amp C enzymes.

Resistance to third-generation cephalosporins mediated by beta-lactamases is an increasing problem for clinical therapeutics. A wide range of Enterobacteriaceae produce these AmpC enzymes (Bush-Jacoby-Medeiros group 1), including Enterobacter spp., Citrobacter freundii, Morganella morganii, Providencia spp., and Serratia marcescens. Resistance via this mechanism has been shown to be statistically correlated with the use of some third-generation cephalosporins, and the infections caused by these stably derepressed enzyme-producing species seem to occur most frequently in the seriously ill. More recently the genes encoding this enzyme have been documented on plasmids capable of transfer into other species such as Klebsiella pneumoniae. Fourth-generation cephalosporins, with stability and low affinity for the Amp C beta-lactamases and the ability to penetrate rapidly into the periplasmic space of Gram-negative organisms, offer a viable alternative in the treatment of these infections or as empiric regimens. Furthermore, these compounds (example: cefpirome) possess greater potency against the frequently occurring Gram-positive cocci such as oxacillin-susceptible staphylococci and the streptococci (including some penicillin-resistant strains) as compared to previously used anti-pseudomonal cephalosporias, ceftazidime.

Bacterial Proteins↗

PubMed1998

Bacterial resistance: a worldwide problem.

The therapeutic crisis produced by emerging antimicrobial resistances has compromised the chemotherapy of hospitalized patients with serious infections. For the most prevalent resistance problems, meropenem, a new carbapenem, appears to provide a potency and spectrum for: 1) extended-spectrum beta-lactamase-producing Enterobacteriaceae; 2) Bush-Jacoby-Merdeiros group 1 enzyme-producing ceftazidime-resistant Enterobacter spp., Citrobacter freundii, and some Serratia spp.; 3) ceftazidime- and imipenem-resistant Pseudomonas aeruginosa; and 4) some Streptococcus spp. with elevated penicillin MICs. Documented in vitro study results using 1997 gram-negative blood stream infection isolates indicate a wider spectrum and a two- to fourfold greater potency for meropenem compared with imipenem. This was especially true for P. aeruginosa where 93.4% of strains were susceptible to meropenem (84.1% for imipenem). Also among over 30,000 reported in vitro meropenem results from the United States and Europe, 90.6% of gram-positive cocci and 99.1% of anaerobes were inhibited at < or = 4 microg/ml. Over 90% of ceftazidime-resistant blood stream infection strains were meropenem susceptible, a rate greater than those of imipenem, ciprofloxacin, and gentamicin. As the clinical utility of many contemporary antimicrobial agents is challenged by emerging resistance, the carbapenems (meropenem, imipenem) appear positioned for a greater role in the treatment of infections in hospitalized patients.

Bacteria↗

PubMed1998

Activity of a broad-spectrum cephalosporin (Ro 48-8391) alone and in combination with two novel beta-lactamase inhibitors (Ro 48-5545 and Ro 48-8724).

The susceptibility of a group of beta-lactamase-producing and drug-resistant Gram-positive and Gram-negative organisms was tested against a novel cephalosporin (Ro 48-8391) alone and in combination with two bridged carbacephem beta-lactamase inhibitors (Ro 48-5545 or Ro 48-8724) and compared with that of ceftriaxone, ceftazidime, and cefepime (representative "third- and fourth-generation" cephalosporins), imipenem, and a combination of piperacillin and tazobactam. Five hundred and one selected clinical isolates were tested using the reference broth microdilution method (National Committee for Clinical Laboratory Standards). Ro 48-8391 has a spectrum of activity and potency most similar to ceftriaxone but with improved activity against Gram-positive species. The two beta-lactamase inhibitors, Ro 48-5545 and Ro 48-8724, have modest antimicrobial activity. When combined with Ro 48-8391, the beta-lactamase inhibitor Ro 48-8724 was superior to the combination of Ro 48-8391 and Ro 48-5545 in spectrum and enzyme inhibition against extended spectrum beta-lactamase enzyme-producing Escherichia coli and Klebsiella pneumoniae, and against Enterobacteriaceae with "stably derepressed" Bush-Jacoby-Medeiros gr 1 enzymes (ceftazidime-resistant Enterobacter and Citrobacter). Ro 48-5545 and Ro 48-8724 appear to be promising beta-lactamase inhibitors with potential application against chromosomal- and plasmid-mediated enzymes. Ro 48-8391, although superior to some currently available "third-generation" cephems, was not a well-matched active codrug because of limited activity against several commonly isolated species of clinically important bacteria. Further efforts are necessary to find a penicillin or cephem with activity more complementary to that of the tested beta-lactamase inhibitors and the Ro 48-8391 compound could be focused for therapeutic use in serious streptococcal infections.

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

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

In vitro susceptibility to pexiganan of bacteria isolated from infected diabetic foot ulcers.

During two clinical trials involving the treatment of 835 outpatients with infected diabetic foot ulcers, 2515 bacterial isolates, including 2337 aerobes and 178 anaerobes, were grown from cultures of the ulcers. The in vitro susceptibility of these isolates was determined to pexiganan, a peptide anti-infective evaluated in these clinical trials, and to other classes of antibiotics. Pexiganan demonstrated broad spectrum antimicrobial activity against Gram-positive and Gram-negative aerobes and anaerobes. The MIC90 values for the most common species among 1735 Gram-positive aerobes isolated, such as Staphylococcus aureus, coagulase-negative staphylococci, Group A streptococci, and Group B streptococci, were 16 micrograms/mL or less. Of 602 Gram-negative aerobes tested, the MIC90 values for pexiganan were 16 micrograms/mL or less for Acinetobacter, Pseudomonas, Stenotrophomonas, Citrobacter, Enterobacter, Escherichia, Klebsiella, and Flavobacterium species. Pexiganan had a MIC90 of 4 to 16 micrograms/mL against the anaerobic isolates of Bacteroides, Peptostreptococcus, Clostridium, and Prevotella species. Importantly, pexiganan did not exhibit cross-resistance with other commonly used antibiotics, including beta-lactams, quinolones, macrolides, and lincosamides. The broad spectrum in vitro antimicrobial activity of pexiganan against clinical isolates from infected diabetic foot ulcers supports its potential as a local therapy for infected diabetic foot ulcers.

Adult↗

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

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 broad-spectrum beta-lactams in the philippines medical centers: role of fourth-generation cephalosporins. The Philippines Antimicrobial Resistance Study Group.

Cefepime is a potent broad-spectrum "fourth-generation" cephalosporin. The in vitro activity of cefepime was compared to that of cefpirome, ceftazidime, ceftriaxone, imipenem, and piperacillin/tazobactam in a multilaboratory (nine medical centers) Philippine surveillance project from March through October 1998. A total of 626 Gram-positive and Gram-negative organisms (10 species groups) were tested by the Etest method (AB BIODISK, Solna, Sweden) with results validated by current quality control strain analysis. The overall rank order of usable spectrum of activity was imipenem (4.2% resistance), cefepime (4.5%), cefpirome (5.0%), piperacillin/tazobactam (5.8%) > ceftriaxone (11.2%) > ceftazidime (15.3%), and results did not differ significantly between medical centers. Ceftazidime-resistant Escherichia coli and Klebsiella spp. occurred at rates of 13.3% and 31.1%, respectively, indicating extended-spectrum beta-lactamase (ESBL) activity. Imipenem (100% susceptible), cefepime, and cefpirome (both > or = 97.8% susceptible) were active in vitro against these ESBL phenotypes. Organisms with ceftazidime and/or ceftriaxone-resistant profiles consistent for hyper-production of Amp C cephalosporinases were detected at high rates among the Citrobacter spp. (29.2%) and Enterobacter spp. (45.8%); however, imipenem (100.0% susceptible) and cefepime (98.9%) remained active. Cefepime and imipenem (both 87.5% susceptible) were the most active agents tested against Acinetobacter spp. whereas piperacillin/tazobactam was most effective against P. aeruginosa (80.0% susceptible). Most tested beta-lactams (except ceftazidime) were active versus oxacillin-susceptible staphylococci. These data should be used as a guide for treatment selection with beta-lactam compounds in the Philippines and to serve as a resistance benchmark in comparisons with future studies in this nation.

Bacteria↗

PubMed1999

In vitro evaluation of cefepime and other broad-spectrum beta-lactams in 22 medical centers in Japan: a phase II trial comparing two annual organism samples. The Japan Antimicrobial Resistance Study Group.

An antimicrobial resistance surveillance study in Japan is presented representing the second year (Phase II) results from 22 medical centers. Each participant laboratory tested (Etest, AB BIODISK, Solna, Sweden) 100 organisms, 10 strains each from 10 species groups including Escherichia coli, Klebsiella spp., Enterobacter spp., Citrobacter spp., indole-positive Proteae, Serratia spp., Acinetobacter spp., Pseudomonas aeruginosa, and oxacillin-susceptible Staphylococcus aureus and coagulase-negative staphylococci. Generally only modest variations in the activity of the studied broad-spectrum beta-lactams was observed compared to the study a year before. Specifically, extended spectrum beta-lactamase (ESBL) rates in E. coli increased (2.9 to 8.1%), but the ESBL rate in Klebsiella spp. fell (8.6 to 5.0%). Overall the resistance to the beta-lactams varied from a 4.7% decrease (ceftazidime as a consequence of a modified staphylococcal breakpoint criteria) to a 1.0% increase (cefepime, not significant). The rank order of spectrums in 1998 only changed for cefoperazone-sulbactam (6.1% resistance) that was active against more strains than cefpirome (6.8% resistance). The overall spectrum rank order for the 1998 Japan sample (% resistance) was: cefepime (3.2%) > imipenem (4.1%) > cefoperazone-sulbactam (6.1%) > cefpirome (6.8%) > ceftazidime (8.4%) > piperacillin (19.9%). As with a similar study in 1997, imipenem-resistant isolates of P. aeruginosa and Serratia spp. were discovered with metalloenzymes, usually found in the same medical centers. These results demonstrate the continued in vitro activity and potential sustained clinical efficacy of several broad-spectrum beta-lactams in Japan. Rapid emergence of new or novel resistance were not wide spread using a precise quantitative MIC system. Continued surveillance in this nation would be prudent to document the activity of this clinically valuable class of safe, antimicrobial agents.

Anti-Bacterial Agents↗

PubMed1999

In vitro evaluation of cefepime and other broad-spectrum beta-lactams in eight medical centers in Thailand. The Thailand Antimicrobial Resistance Study Group.

The introduction of cephalosporins has had an important impact on the resistance rates to several clinically utilized beta-lactam antimicrobial agents. Most Thailand medical centers have not documented the levels of emerging resistant pathogens causing invasive infections. This study shows using reference-quality MIC techniques (Etest, AB BIODISK, Solna, Sweden), that carbapenem), "fourth-generation" cephalosporins (cefepime and cefpirome), and piperacillin/tazobactam were the most active agents tested against Gram-negative bacilli (Escherichia coli, Klebsiella spp., Enterobacter spp., Citrobacter spp., Serratia spp., indole-positive Proteae, Acinetobacter spp., Pseudomonas aeruginosa, and oxacillin-susceptible Staphylococcus spp. when compared to "third-generation" cephalosporins (ceftazidime and ceftriaxone). The rank order of activity for all species was imipenem (2.9% resistant) > cefepime (7.7%) > piperacillin/tazobactam (11.1%) > cefpirome (13.4%) > ceftriaxone (21.1%) > ceftazidime (29.9%). The incidence of extended spectrum beta-lactamase production among E. coli (15.7%) and K. pneumoniae (45.6%) was significant. Cefepime and imipenem were active against the majority of these isolates. The activity of cefepime was also shown to be very good against, 1) organisms capable of producing AmpC enzymes, 2) staphylococci species that were susceptible to oxacillin, and 3) many strains of nonfermentative Gram-negative bacilli. The prevalence of antimicrobial resistance in Thailand seems to be quite high among certain commonly encountered pathogens, and imipenem and cefepime have activity (susceptible and intermediate potency) against > 90% of these organisms.

Anti-Bacterial Agents↗

PubMed1999

In vitro evaluation of broad-spectrum beta-lactams tested in medical centers in Korea: role of fourth-generation cephalosporins. The Korean Antimicrobial Resistance Study Group.

Levels of resistance to the "third-generation" cephalosporins among isolates of clinical bacteria in Korea have been increasing at a rapid rate. This study evaluated the activity of cefepime, a "fourth-generation" cephalosporin, and six other broad-spectrum beta-lactam antimicrobials (cefpirome, ceftazidime, ceftriaxone, imipenem, piperacillin/tazobactam 4 micrograms/mL fixed concentration[, oxacillin) against 404 isolates of clinical bacteria from Korea. Susceptibility profiles of each isolate were established using the Etest (AB BIODISK, Solna, Sweden) method of susceptibility testing. Only the carbapenem imipenem was > 90% effective in inhibiting each of the species tested (Escherichia coli, Klebsiella, spp., Citrobacter spp., Enterobacter spp., indole-positive Proteae, Serratia spp., Acinetobacter spp., Pseudomonas aeruginosa, and oxacillin-susceptible staphylococci). Imipenem was followed by cefepime > cefpirome > piperacillin/tazobactam > ceftazidime > ceftriaxone in overall rank order of usable spectrum against the isolates tested. Extended spectrum beta-lactamase producing phenotypes were much more prevalent among the Klebsiella spp. (48.8%) than the E. coli (5.0%) isolates. Cefepime was much more active than cefpirome, 95.1% susceptible as compared with 70.7% susceptible, against the 41 isolates of Klebsiella spp. The results of this study corroborates findings from earlier studies with levels of resistance to the broad-spectrum beta-lactams in Korea continuing to rise indicating the need for intervention strategies.

Cefepime↗

PubMed2000

In vitro activity of 19 antimicrobial agents against 3513 nosocomial pathogens collected from 48 Canadian medical centres. The Canadian Antimicrobial Study Group.

Antimicrobial resistance is a global concern. Differentiation between susceptibility rates for nosocomial versus community pathogens is important epidemiologically because it impacts on the appropriate empirical selection of antimicrobial therapy for infected patients. We studied resistance rates for 3513 nosocomial pathogens from 48 Canadian medical centres tested against 19 antimicrobial agents. The following are percent susceptibility for ceftazidime, ceftriaxone, ciprofloxacin, imipenem, netilmicin, and ticarcillin/clavulanic acid, respectively: Enterobacteriaceae 95, 95, 97, 99 98, 89; Escherichia coli, all 99 except ticarcillin/clavulanic acid (91); Enterobacter spp. 78, 78, 96, 99, 99, 71; Citrobacter spp. 79, 80, 89, 100, 94, 73; Proteus spp. 99, 88, 99, 88, 99, 98; Pseudomonas aeruginosa 88, 20, 82, 88, 81, 36; Staphylococcus aureus, all > 95; Enterococcus spp. 4, 9, 62, 95, 43, 38. Susceptibility rates for other species of microorganisms and agents tested varied considerably. Some institutions had higher than average resistance rates for some pathogens (i.e. P. aeruginosa) and some agents. Detection and continued surveillance of antimicrobial resistance amongst nosocomial pathogens is vital to patient care and health care resources. The control of antimicrobial resistance can help maintain antibiotic usage and costs associated with the use of ever more potent drugs and the treatment of increasingly resistant infections.

Canada↗

PubMed2000

Susceptibility of bacterial isolates to gatifloxacin and ciprofloxacin from clinical trials 1997-1998.

MICs of gatifloxacin and ciprofloxacin against 3482 pre-treatment, clinical trial isolates collected during 1997-1998 are reported. These data suggested that gatifloxacin was four- to eight-fold more active than ciprofloxacin against Gram-positive bacteria, with gatifloxacin MIC(90)s < or = 0.33 mg/l against Staphylococcus aureus and Streptococcus pneumoniae, and < or = 1.0 mg/l versus viridans streptococci and Enterococcus faecalis. Both quinolones had similar MIC(90)s versus Enterobacteriaceae (generally < or = 0.38 mg/l, except 0. 7-0.8 mg/l for Citrobacter freundii) and Pseudomonas aeruginosa ( approximately 8 mg/l). A total of 78% P. aeruginosa had gatifloxacin MICs < or = 2 mg/l. Gatifloxacin was more active than ciprofloxacin against Acinetobacter species and non-P. aeruginosa pseudomonads. Both had exceptional activity versus Haemophilus spp, Moraxella catarrhalis and Neisseria gonorrhoeae. In summary, compared to ciprofloxacin, gatifloxacin had improved activity against Gram-positive bacteria and comparable activity against Gram-negative bacteria.

Anti-Infective Agents↗

PubMed2001

The in vitro activity of sulbactam combined with third generation cephalosporins against third generation cephalosporin-resistant bacteria.

The in vitro activity of the beta-lactamase inhibitor sulbactam combined with cefuroxime, cefotaxime or ceftazidime in the ratio of 1:1 was studied against ceftazidime- or cefuroxime-resistant Gram-negative rods and Staphylococcus aureus. Sulbactam enhanced the antibacterial activities of cefuroxime, cefotaxime and ceftazidime against Gram-negative rods. The MIC(90) of ceftazidime against Escherichia coli, Enterobacter cloacae, Citrobacter freundii, Acinetobacter spp. and Pseudomonas aeruginosa was reduced 4-fold and that of cefotaxime against E. coli, E. cloacae, C. freundii and Acinetobacter spp. reduced by 2-4-fold. However, sulbactam did not enhance the activities of cefuroxime, cefotaxime or ceftazidime against S. aureus, enterococci and Stenotrophomonas maltophilia. With the combination of sulbactam and ceftazidime at the ratio of 1:1, 38.4% of E. coli, 45.3% of E. cloacae, 66.6% of C. freundii and 60% of Acinetobacter spp. initially resistant to ceftazidime became susceptible.

Cephalosporin Resistance↗