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PubMed2002

Broad resistance due to plasmid-mediated AmpC beta-lactamases in clinical isolates of Escherichia coli.

Escherichia coli that produce plasmid-mediated AmpC beta-lactamases are rare in the United States. The clinical features associated with infection with these organisms have not been well described. We identified 2 clinical isolates of E. coli that produced the plasmid-mediated AmpC enzyme beta-lactamase CMY-2. These organisms were recovered from urine specimens and were resistant to ceftazidime, ceftriaxone, and cefepime. One isolate was resistant to ertapenem but susceptible to imipenem and meropenem; the other was susceptible to imipenem, meropenem, and ertapenem. One of the 2 infected patients did not require specific therapy; the other required imipenem for cure. The presence of the CMY-2 beta-lactamase was confirmed by DNA sequencing. Hybridization studies confirmed that the bla(CMY-2) gene was on a plasmid in both isolates; in one of them, the probe also hybridized with chromosomal DNA. Infection with plasmid-mediated AmpC beta-lactamases in E. coli in the United States may be associated with treatment failure, and these strains may become a serious nosocomial threat.

Adult↗

PubMed2004

Incidence of carbapenem-associated allergic-type reactions among patients with versus patients without a reported penicillin allergy.

This retrospective analysis sought to determine the comparative incidence of cross-reactivity associated with carbapenem antibiotic treatment among patients with versus those without penicillin allergy. We sought to determine whether the incidence of cross-reactivity is different between imipenem-cilastatin and meropenem. A total of 211 patients were treated with a carbapenem antibiotic. Included were 100 patients with and 111 patients without a documented or reported penicillin allergy. Within each group, subgroups of penicillin-allergic and penicillin-nonallergic patients were balanced equally between imipenem-cilastatin and meropenem. The incidence of patients with a reported or documented penicillin allergy experiencing an allergic-type reaction to a carbapenem was 11%, which is 5.2 times greater than the risk in patients who were reportedly not allergic to penicillin (P=.024). No difference in the occurrence of allergic-type reactions was observed between the 2 carbapenems.

Adolescent↗

PubMed1998

In vitro antibiotic synergy against Flavobacterium meningosepticum: implications for therapeutic options.

Flavobacterium meningosepticum is an unusual, highly resistant, gram-negative bacillus that is associated with neonatal meningitis and nursery outbreaks of meningitis. The optimal therapy for this infection is not known. We successfully treated three neonates with intravenous vancomycin and rifampin. We determined the in vitro activity of meropenem, ciprofloxacin, vancomycin, linezolid (PNU-100766), and rifampin, alone and in combination, against four isolates of F. meningosepticum from neonates with sepsis and meningitis. MICs were determined by tube dilution, and fractional inhibitory concentrations were calculated with use of the checkerboard microtiter dilution technique. Synergy was observed between rifampin and vancomycin against three isolates, while combinations of vancomycin, ciprofloxacin, and linezolid showed an additive effect against all isolates. These results support the clinical evidence that the combination of vancomycin and rifampin is an appropriate regimen for neonatal meningitis due to F. meningosepticum. The combination of meropenem and vancomycin was antagonistic. The clinical efficacy of combinations including ciprofloxacin, newer quinolones, or linezolid for treating F. meningosepticum meningitis deserves further study.

Drug Synergism↗

PubMed1999

Decreased production of AmpC-type beta-lactamases associated with the development of resistance to quinolones in Citrobacter freundii strains.

The effect of fluoroquinolones in Citrobacter freundii strains that results in a decreased expression of cephalosporin-hydrolysing beta-lactamases was studied. Resistance to broad-spectrum cephalosporins and penicillins in two C. freundii clinical isolates was associated with moderate production of chromosomal AmpC-type-beta-lactamase in addition to changes in the outer membrane proteins profile with respect to wild-type C. freundii strains. Ten quinolone-resistant mutants were derived from the two clinical isolates using increasing fluoroquinolone concentrations. The level of susceptibility to cephalosporins and meropenem of these 10 mutants was increased and was associated with a 3.6-32% diminution in the hydrolyzing activity of their periplasmic extracts containing beta-lactamases on cephaloridine as compared with those from their parent strains. Susceptibility to cephalosporins and meropenem, as well as the expression of chromosomal AmpC-type-beta-lactamase in C. freundii strains, was influenced by the exposure to quinolones.

Anti-Infective Agents↗

PubMed2005

In vitro activities of tigecycline, ertapenem, isepamicin, and other antimicrobial agents against clinically isolated organisms in Taiwan.

This study evaluated the in vitro activities of tigecycline, ertapenem, isepamicin, and other comparators against 861 bacterial isolates recovered from patients treated in three major teaching hospitals in 2003. MICs to antimicrobial agents were determined by the agar dilution method. High rates of oxacillin resistance (58%) in Staphylococcus aureus (60 isolates), and vancomycin resistance (21%) and quinupristin-dalfopristin non-susceptibility (39%) in Enterococcus faecium (34 isolates) were found. Carbapenems had excellent in vitro activities (>or=98% susceptibility) against the 419 isolates of Enterobacteriaceae, with the MIC(50) and MIC(90) of imipenem, meropenem, and ertapenem being 0.25 and 4 mg/L, 0.03 and 0.12 mg/L, and 0.03 and 0.5 mg/L, respectively. For, Pseudomonas aeruginosa (74 isolates) and Burkholderia cepacia (21 isolates), meropenem (MIC(90), 0.25, 2, and 4 mg/L, respectively) had better in vitro activities than imipenem (MIC(90), 8, 4, and 32 mg/L, respectively) and ertapenem (MIC(90), 0.5, >32, and 32 mg/L, respectively). Isepamicin had a similar activity with amikacin against all Enterobacteriaceae, Pseudomonas aeruginosa, B. cepacia, and Acinetobacter baumannii, except for C. freundii isolates in which isepamicin had an eight-fold activity better than amikacin. Tigecycline had excellent in vitro activities against all isolates tested (MIC(90), <or=1 mg/L) including 14 pandrugresistant A. baumannii isolates (MICs, 1-4 mg/L), except for Proteus mirabilis (59 isolates; MIC(90), 8 mg/L), Bacteroides fragilis (60 isolates; MIC(90), 8 mg/L), P. aeruginosa (MIC(90), 16 mg/L), and B. cepacia (21 isolates; MIC(90), 16 mg/L). Tigecycline, carbapenems, and isepamicin exhibited better or comparable in vitro activities against a wide spectrum of commonly encountered bacteria than other comparator antimicrobials and may represent therapeutic options for infections due to multidrug-resistant pathogens.

Anti-Bacterial Agents↗

PubMed2005

Empiric treatment of nosocomial intra-abdominal infections: a focus on the carbapenems.

BACKGROUND: Serious nosocomial intra-abdominal infections are associated with high morbidity and mortality and represent a substantial drain on healthcare resources. Effective management of this type of infection requires the early use of appropriate, broad-spectrum empiric antimicrobial therapy. The consequences of delayed or inappropriate antimicrobial treatment can be severe-leading to an increased risk of death, re-operation, or prolonged hospitalization. Therefore, it is necessary to begin treatment as soon as possible with the most appropriate regimen, in terms of spectrum, timing, and duration. METHODS: Review of pertinent English-language literature. RESULTS: Serious nosocomial intra-abdominal infections require broad-spectrum coverage because of the wide range of possible pathogens, which include difficult-to-treat organisms such as Pseudomonas aeruginosa and Bacteroides spp., and resistant strains of Klebsiella spp., Escherichia coli, and methicillin-resistant Staphylococcus aureus acquired from the hospital flora. The early use of appropriate, broad-spectrum empiric antimicrobial therapy for treating high-risk patients with intra-abdominal infections is considered, and appropriate use of the carbapenems, meropenem, and imipenem/cilastatin, is described. CONCLUSION: The carbapenems meropenem and imipenem/cilastatin have a spectrum of antimicrobial activity that covers the majority of expected pathogens, including anaerobes, as well as difficult-to-treat and resistant gram-negative strains. Early and appropriate use can reduce mortality and morbidity. Data from published clinical trials support the clinical effectiveness of these two carbapenems in intra-abdominal infections.

Abdominal Cavity↗

PubMed2006

Antimicrobial resistance of Pseudomonas aeruginosa strains isolated from surgical infections in a 7-year period at a general hospital in Venezuela.

BACKGROUND: By definition, the term "surgical infection" implies that surgery plays the major role in therapy, whereas antimicrobial chemotherapy is only supplementary. Despite this view, the efficacy of such drugs is relevant, and for this reason, drug activity surveillance is necessary, especially for opportunistic and nosocomial pathogens such as Pseudomonas aeruginosa. We evaluated bacterial isolates from patients with suspected surgical infections in a hospital of Caracas, Venezuela (West General Hospital) between 1997 and 2003. METHODS: Clinical samples were processed and identified with standard cultures and biochemical tests. The antimicrobial susceptibility of the isolates in vitro was assessed by an agar disk diffusion method using Mueller-Hinton agar, as recommended by the National Committee for Clinical Laboratory Standards (now the Clinical and Laboratory Standards Institute). Isolates were tested against 22 drugs, including piperacillin, ceftazidime, cefoperazone, amikacin, gentamicin, ciprofloxacin, meropenem, and imipenem. RESULTS: From a total of 16,287 bacterial strains isolated from surgical infections during the study period, 243 (1.5%) were P. aeruginosa. Of this total, 30.9% were resistant to gentamicin, 26.3% to tobramicin, 23.0% to cefoperazone, 22.8% to piperacillin, 22.5% to ciprofloxacin, 17.6% to amikacin, 13.6% to imipenem, and 12.9% to meropenem. The best antimicrobial activity was observed with cefepime (90.1% susceptible strains, 1.9% intermediate resistance, and 8.0% resistant strains) and aztreonam (77.7% susceptible strains, 15.2% intermediate resistance, and 7.1% resistant strains). CONCLUSIONS: In our setting, cefepime is most active against strains of P. aeruginosa. In comparison with third-generation cephalosporins, cefepime may be less likely to induce resistance. Surveillance of antimicrobial activity should be done periodically to guide therapy of surgical infections.

Adolescent↗

PubMed1996

Analysis of trends in antimicrobial resistance patterns among clinical isolates of Bacteroides fragilis group species from 1990 to 1994.

Antimicrobial resistance, including plasmid-mediated resistance, among Bacteroides fragilis group species is well documented. A 5-year (1990-1994) prospective, eight-center survey of 3,177 clinical isolates of Bacteroides species was undertaken to review trends in resistance, using the breakpoints for full and intermediate susceptibility established by the National Committee for Clinical Laboratory Standards. No documented resistance to either metronidazole or chloramphenicol was found in this survey. Among B. fragilis isolates virtually no resistance was seen to imipenem, meropenem, ampicillin/sulbactam, piperacillin/tazobactam, or ticarcillin/clavulanate. Significant increases in resistance among B. fragilis isolates to cefotetan, ceftizoxime, and clindamycin (p < .01) were noted. Resistance to cefoxitin remained unchanged. Among the non-fragilis species of the B. fragilis group, there was virtually no resistance to imipenem, meropenem, chloramphenicol, or metronidazole. The three beta-lactamase inhibitors had increasing levels of resistance, although 95%-98% of strains were susceptible (p < .05). There was a significant decline in cefoxitin, cefmetazole, and clindamycin activity over time against these strains (p <.01). There was a significant (P < .001) increase in geometric mean minimum inhibitory concentration for most drugs and species tested from 1990 to 1994. Clusters in the eight institutions could not account for this rise in resistance. This survey demonstrates that rates of resistance of B. fragilis and non-fragilis species of B. fragilis group are increasing.

Bacteroides↗

PubMed1990

Response of chemostat cultures of Pseudomonas aeruginosa to carbapenems and other beta-lactams.

Cultures of Pseudomonas aeruginosa were grown at different rates in a chemostat and challenged continuously or intermittently with ceftazidime, imipenem, meropenem or piperacillin. The killing rate was related to the bacterial growth rate; fast-growing cells being killed more rapidly than slow-growing ones. Mutants that were stably derepressed (i.e. constitutive) for chromosomal beta-lactamase expression were selected when a beta-lactamase inducible (i.e. typical) strain was challenged with ceftazidime or piperacillin. Addition of the beta-lactamase inhibitor tazobactam to piperacillin did not prevent selection. There was a lag of c. 24-48 h post-challenge before totally derepressed mutants were detectable. Once selected, the derepressed organisms were stable and were not outgrown by inducible cells if these were readded in the absence of selective antibiotics. Selection of resistant mutants was not observed with imipenem, despite the known tendency of this drug to select carbapenem-impermeable mutants of P. aeruginosa in vivo. Imipenem, but not ceftazidime or meropenem, caused a significant post-antibiotic effect after single or repeated dosage.

Anti-Bacterial Agents↗

PubMed1990

Selection and transformation of non-beta-lactamase-mediated insusceptibility to beta-lactams in Haemophilus influenzae: lack of cross-resistance between carbapenems and other agents.

Non-beta-lactamase-mediated insusceptibility to beta-lactams was studied in Haemophilus influenzae. Mutants resistant to ampicillin were selected in a susceptible isolate, while phenotypically similar resistance was transformed from four wild-type isolates into a susceptible recipient. Ampicillin-selected mutants generally had reduced susceptibility to penicillins, cephalosporins and aztreonam. Reduced susceptibility to meropenem was less common, and susceptibility to imipenem was unaffected. MICs of three cephalosporins and aztreonam were much higher for the ampicillin-resistant transformants than for the recipient strain, and were generally equal to, or within one doubling dilution of, the concentrations that inhibited the donor parents. In contrast, reduced susceptibility to imipenem observed with one parent (MIC of 4 mg/l) was not transferred to the recipient (MIC of 0.5 mg/l). Meropenem inhibited 22 of 24 transformants tested at less than or equal to 0.12 mg/l, compared with MICs of greater than or equal to 0.5 mg/l for the donor parents and 0.03 mg/l for the recipient. These results indicated that the mechanisms that confer non-beta-lactamase-mediated insusceptibility to penicillins, cephalosporins and aztreonam in H. influenzae have little or no effect on susceptibility to carbapenems.

Ampicillin Resistance↗

PubMed1991

Role of OmpD2 and chromosomal beta-lactamase in carbapenem resistance in clinical isolates of Pseudomonas aeruginosa.

Imipenem-resistant clinical isolates of Pseudomonas aeruginosa were divided into two categories: (i) isolates that were moderately resistant to imipenem (MIC 6.25 mg/L) that produced trace amounts of protein D2 detected with immunoblotting using anti-protein D2 antibody, but not when stained with Coomassie blue and had inducible class 1 beta-lactamase expression; (ii) isolates that were highly resistant to several beta-lactams, including meropenem, with no protein D2 by staining or immunoblotting and had stably derepressed beta-lactamase. Laboratory strains were isolated and analyzed: (i) mutants lacking protein D2, or (ii) lacking protein D2 and producing stably derepressed beta-lactamase with carbapenem resistance similar to the clinical isolates. (iii) mutants producing undetectable beta-lactamase which were four-fold more susceptible to imipenem than the mutant producing stably derepressed beta-lactamase or the strain with inducible beta-lactamase. These data suggests that beta-lactamase and outer membrane permeability govern meropenem-resistance in P. aeruginosa.

Bacterial Outer Membrane Proteins↗

PubMed2000

Activity and spectrum of 22 antimicrobial agents tested against urinary tract infection pathogens in hospitalized patients in Latin America: report from the second year of the SENTRY antimicrobial surveillance program (1998).

The potency and spectrum of various antimicrobial agents tested against 434 bacterial isolates causing urinary tract infection (UTI) in hospitalized patients in Latin America were evaluated. The genotypes of the extended-spectrum beta-lactamase-producing and selected multi-resistant isolates were also evaluated by molecular typing techniques. Escherichia coli (60.4%) was the most common aetiological agent causing UTI, followed by Klebsiella spp. (11.2%) and Pseudomonas aeruginosa (8.3%). In contrast, Enterococcus spp. isolates caused only 2.3% of UTIs. Fewer than 50% of E. coli isolates were susceptible to broad-spectrum penicillins. The resistance rates to ciprofloxacin and the new quinolones were also high among these isolates. The molecular characterization of ciprofloxacin-resistant E. coli showed that most of them have a double mutation in the gyrA gene associated with a single mutation in the parC gene. The Klebsiella pneumoniae isolates studied demonstrated high resistance rates to beta-lactam drugs, including broad-spectrum cephalosporins. The carbapenems were the compounds with the highest susceptibility rate among these isolates (100.0% susceptible) followed by cefepime (91.7% susceptible). Meropenem, imipenem and cefepime were also the most active drugs against Enterobacter spp. Among P. aeruginosa isolates, meropenem (MIC(50), 2 mg/L) was the most active compound, followed by imipenem (MIC(50), 4 mg/L), cefepime (MIC(50), 8 mg/L) and ceftazidime (MIC(50), 16 mg/L). The results presented in this report confirm that bacterial resistance continues to be a great problem in Latin American medical institutions.

Anti-Bacterial Agents↗

PubMed2002

In vitro activity of the aerosolized agents colistin and tobramycin and five intravenous agents against Pseudomonas aeruginosa isolated from cystic fibrosis patients in southwestern Germany.

Three hundred and eighty-five mucoid and non-mucoid strains of Pseudomonas aeruginosa isolated from 192 sputa from 57 adult cystic fibrosis patients were studied. Susceptibility testing using an agar dilution technique was performed for ceftazidime, ciprofloxacin, fosfomycin, meropenem and piperacillin, and the aerosolized agents colistin and tobramycin. Meropenem, ceftazidime and piperacillin were the most potent agents (susceptibility 86.2%, 84.2% and 84%, respectively). Tobramycin and colistin susceptibility rates were lower, but in light of higher intrabronchial concentrations of these drugs a greater percentage of strains might still be clinically susceptible. Only 46.2% and 41.8% of isolates were susceptible to ciprofloxacin and fosfomycin, respectively.

Aerosols↗

PubMed2025

Phenotypic and genotypic profiles of clinical isolates of various Nocardia species to carbapenems and fluoroquinolones.

OBJECTIVES: To establish patterns of the antimicrobial susceptibility of Nocardia species to carbapenems and fluoroquinolones and analysis of phenotypic-genotypic correlations. METHODS: Isolates were identified to the species using 16S rRNA, secA1, or rpoB gene sequencing analysis. The antimicrobial susceptibility testing was performed using the broth microdilution method, and WGS was employed to analyse the presence of resistance genes and/or mutations of Nocardia species against carbapenems and fluoroquinolones. RESULTS: Among 143 Nocardia isolates, N. farcinica (27.27%, 39/143) and N. cyriacigeorgica (25.17%, 36/143) were the most common species, followed by N. abscessus Complex (18.88%, 27/143). The MIC90s of the seven carbapenems were 8 mg/L for doripenem, 8 mg/L for meropenem, 16 mg/L for ertapenem, 16 mg/L for biapenem, 64 mg/L for imipenem, 64 mg/L for faropenem and 128 mg/L for tebipenem, respectively. The susceptibility rates to imipenem were 76.9% and 88.9% for N. farcinica and N. cyriacigeorgica, respectively, but only 14.3% and 0% for N. otitidiscavarium and N. brasiliensis, respectively. Further, 90% of N. brasiliensis and 50% of N. otitidiscaviarum isolates were susceptible and intermediate to meropenem. WGS identified blaFAR-1 gene in N. farcinica and blaAST-1 gene in N. cyriacigeorgica, respectively. The MIC90s of the four fluoroquinolones were 1 mg/L for sitafloxacin, 4 mg/L for nemonoxacin, 4 mg/L for moxifloxacin and 16 mg/L for ciprofloxacin, respectively. The susceptibility rate of Nocardia species to ciprofloxacin was low except for N. farcinica. The resistance to fluoroquinolones arise from mutations in the gyrA gene. CONCLUSIONS: Nocardia spp. exhibited varying patterns of susceptibility to carbapenems and fluoroquinolones respectively. Importantly, different Nocardia spp. exhibited different patterns of susceptibility to carbapenems and fluoroquinolones, respectively.

Nocardia↗

PubMed2025

Mechanisms of resistance to ceftazidime/avibactam in mutants derived in vitro from Klebsiella pneumoniae producing OXA-48-like enzymes.

OBJECTIVES: To generate in vitro ceftazidime-avibactam-resistant mutants derived from Klebsiella pneumoniae producing OXA-48 or OXA-48 derivatives OXA-131 and OXA-232 carbapenemases, to define their antimicrobial susceptibility phenotype and to analyse mutations potentially involved in resistance to ceftazidime-avibactam. METHODS: Mutants were obtained by plating overnight bacterial cultures on Mueller-Hinton agar plates containing increasing concentrations of ceftazidime-avibactam (0.5/4-32/4 mg/L). MICs were determined using Sensititre™ DKMNG panels. Whole-genome sequencing of 8 parental strains and 31 mutant derivatives was performed with Illumina. RESULTS: All parental strains were susceptible to ceftazidime-avibactam (MIC ≤ 0.5/4-2/4 mg/L) and either susceptible or resistant to meropenem (MIC 0.5 to >16 mg/L) and imipenem (MIC ≤ 0.5 to >16 mg/L). MICs of ceftazidime-avibactam for the mutants increased up to 4 to >16 mg/L, while MICs of meropenem and imipenem for most mutants either increased up to >16 mg/L or remained unchanged. Whole-genome sequencing of the mutants identified alterations in genes coding for proteins related to AcrAB-TolC (AcrB, AcrR), PBPs (PBP2, PBP3), porins (OmpK36, EnvZ) or the stress or stringent responses (RseB, CpxA, SpoT). No mutations were detected in genes coding for OXA-48-like enzymes or other β-lactamases. CONCLUSIONS: Ceftazidime-avibactam can select in vitro mutants of OXA-48-like carbapenemase-producing K. pneumoniae resistant to this combination and, in some cases, also to carbapenems. No mutations related to ceftazidime-avibactam resistance were found in genes coding OXA-48-like enzymes, but they were detected in genes related to active efflux, PBPs, permeability or proteins of the stress and stringent responses.

Ceftazidime↗

PubMed2003

Plasmid-mediated, carbapenem-hydrolysing beta-lactamase, KPC-2, in Klebsiella pneumoniae isolates.

Four isolates of Klebsiella pneumoniae obtained from patients at a Maryland medical centre exhibited reduced susceptibility to carbapenems and were found to produce the novel, class A, plasmid-mediated, carbapenem-hydrolysing enzyme, KPC-2. This enzyme has 99% identity with the plasmid-mediated, carbapenem-hydrolysing enzyme KPC-1, reported previously in a North Carolina K. pneumoniae isolate. The KPC-2-producing isolates were either susceptible or intermediate to imipenem and meropenem, unlike the KPC-1-producing isolate, which was resistant to these agents. Detection of KPC-2 may be a problem for clinical laboratories because in this study it was associated with positive extended-spectrum beta-lactamase (ESBL) confirmation tests (clavulanate-potentiated activities of ceftriaxone, ceftazidime, cefepime and aztreonam). Therefore, a failure to recognize the significance of reduced carbapenem susceptibility in the isolates that remained susceptible to imipenem or meropenem could have resulted in the isolates being incorrectly identified as ESBL producers.

Carbapenems↗

PubMed2004

Contribution of integrons, and SmeABC and SmeDEF efflux pumps to multidrug resistance in clinical isolates of Stenotrophomonas maltophilia.

OBJECTIVES: The contribution of integrons and efflux pumps to multidrug resistance in Stenotrophomonas maltophilia was evaluated. MATERIALS AND METHODS: Ninety-three S. maltophilia clinical isolates were studied. PCR and direct sequencing were used to detect the presence of integrons. Real-time PCR was performed to assess and quantify the expression of the Sme efflux pumps of S. maltophilia. RESULTS: Class 1 integrons were detected in 22% of clinical isolates and carried cassettes conferring resistance mainly to aminoglycosides and trimethoprim. The small multidrug resistance gene, smr, was found on class 1 integrons in six isolates. Thirty-one percent of the isolates overexpressed the smeDEF gene, as compared with a control strain, and 59% overexpressed the smeABC gene. Extrusion of ciprofloxacin and meropenem was specific to the SmeABC and SmeDEF pumps, respectively. CONCLUSION: SmeABC and SmeDEF efflux pumps play important roles in resistance of S. maltophilia to ciprofloxacin and meropenem.

Anti-Bacterial Agents↗

PubMed2004

CS-023 (R-115685), a novel carbapenem with enhanced in vitro activity against oxacillin-resistant staphylococci and Pseudomonas aeruginosa.

OBJECTIVE: To compare the in vitro activities of the carbapenem, CS-023, four representative beta-lactam antibiotics and levofloxacin, against 970 Gram-positive or Gram-negative US clinical isolates. METHODS: Susceptibilities of bacteria chosen for their varying levels of resistance to the comparator agents were determined by NCCLS microdilution methodology. RESULTS: CS-023 exhibited activity comparable to that of imipenem against most Gram-positive isolates, but was approximately 8-fold more potent against oxacillin-resistant staphylococci. It was comparable to meropenem against most Gram-negative isolates, but was 4- to 8-fold more potent against five isolates of meropenem-resistant Pseudomonas aeruginosa. CONCLUSIONS: If tissue and body fluid concentrations >8 mg/L can safely be achieved, further studies of CS-023 are warranted to determine its clinical efficacy.

Anti-Infective Agents↗