The activity of BMY 28142 a new broad spectrum β-lactamase stable cephalosporin

Neu, Harold C.; Chin, Nai-Xun; Jules, K; Labthavikul, Porupen

doi:10.1093/jac/17.4.441

Cited by 41 publications

(30 citation statements)

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“…Cefepime is well tolerated and appears to be comparable to ceftazidime in treatment of skin or wound infections and nosocomial UTIs in hospitalized patients. Although ceftazidime is more active in vitro against P. aeruginosa than cefepime is (2,5,7), clinical and bacteriologic responses for this pathogen were equivalent in this study. Larger studies are required to confirm the relative efficacies of cefepime and ceftazidime in diabetic subjects with infection due to P. aeruginosa.…”

Section: Discussionmentioning

confidence: 56%

“…Strains of Enterobacter spp., S. marcescens, and Citrobacterfreundii which may be resistant to other cephalosporins such as ceftazidime and cefotaxime are frequently very susceptible to cefepime (3,(5)(6)(7). During the course of this study, one prospective subject was found to have a surgical wound infected with ceftazidime-resistant, cefepime-susceptible Enterobacter cloacae and was compassionately treated for 7 days with cefepime, which effected a cure of the infection.…”

Section: Discussionmentioning

confidence: 99%

“…(3,(5)(6)(7); these pathogens tend to be overwhelming producers of P-lactamases, for which cefepime has a low affinity and is resistant to hydrolysis. We undertook an open, randomized comparison of cefepime and ceftazidime in treatment of bacterial infections of the skin and skin structures and urinary tract in hospitalized subjects.…”

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confidence: 99%

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Randomized comparison of cefepime and ceftazidime for treatment of skin, surgical wound, and complicated urinary tract infections in hospitalized subjects

Gentry

Rodriguez-Gomez

1991

Antimicrob Agents Chemother

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We undertook a prospective, randomized open comparison of the broad-spectrum cephalosporins cefepime and ceftazidime in treatment of hospitalized subjects with skin or wound infections and complicated nosocomial urinary tract infections. Cefepime treatment (dosage, 2.0 g intravenously twice daily for 4 to 28 days) was successful in 36 (90%) of 40 infections of the skin and skin structure or wounds and in 16 (84%) of 19 nosocomial urinary tract infections. Ceftazidime treatment, 2.0 g every 8 h, was successful in 34 (96%) of 36 infections of the skin and skin structure and in 15 (88%) of 17 urinary tract infections. Microbiological eradication rates of each agent overall and for Pseudomonas aeruginosa were greater than 90%. In the cefepime group, one death occurred, contributed to by an enterococcal superinfection acquired during study drug therapy, and there were two mild and transient adverse experiences observed. Cefepime was comparable to ceftazidime in treatment of infections of the skin and skin structure requiring hospitalization and of complicated nosocomial urinary tract infections.Cefepime, a novel alpha-methoxyimino aminothiazolyl cephalosporin, is active in vitro against many gram-positive and gram-negative bacteria which are responsible for serious infections (1, 2). Of particular interest are compelling in vitro data establishing that cefepime is active against Pseudomonas aeruginosa (4, 8) and more active than established broad-spectrum cephalosporins against multiply resistant strains of the family Enterobacteriaceae. (3, 5-7); these pathogens tend to be overwhelming producers of P-lactamases, for which cefepime has a low affinity and is resistant to hydrolysis. We undertook an open, randomized comparison of cefepime and ceftazidime in treatment of bacterial infections of the skin and skin structures and urinary tract in hospitalized subjects. MATERIALS AND METHPDSEligible patients for study enrollment included adults hospitalized in St. Luke's Episcopa} Hospital, Houston, Tex., or Hospital Mexico, Sgn Jose, Costa Rica, with culture-proven infections due to bacteria susceptible to both cefepime and ceftazidime. Included were infections of the skin or skin structures which reqijired hospitalization for therapy and complicated nosocomial infections of the urinary' tract which required antibiotic therapy because of fever, positive cultures, and the ahsence of another identified source of infection. fpr the -purposes of this study,

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Section: Discussionmentioning

confidence: 56%

Section: Discussionmentioning

confidence: 99%

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Randomized comparison of cefepime and ceftazidime for treatment of skin, surgical wound, and complicated urinary tract infections in hospitalized subjects

Gentry

Rodriguez-Gomez

1991

Antimicrob Agents Chemother

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“…Whether cefepime can be used is unsettled. Cefepime is a poor inducer of AmpC ␤-lactamase, rapidly penetrates through the outer cell membrane, and is little hydrolyzed by the enzyme (232,283), so many AmpC-producing organisms test cefepime susceptible with a conventional inoculum (see Table 6 for examples). If a 100-fold-higher inoculum is used, however, cefepime MICs increase dramatically for some AmpC producers, suggesting caution in its use (154,256), and some strains are frankly resistant (238).…”

Section: Treatment Of Ampc-producing Organismsmentioning

confidence: 99%

AmpC β-Lactamases

2009

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SUMMARY AmpC β-lactamases are clinically important cephalosporinases encoded on the chromosomes of many of the Enterobacteriaceae and a few other organisms, where they mediate resistance to cephalothin, cefazolin, cefoxitin, most penicillins, and β-lactamase inhibitor-β-lactam combinations. In many bacteria, AmpC enzymes are inducible and can be expressed at high levels by mutation. Overexpression confers resistance to broad-spectrum cephalosporins including cefotaxime, ceftazidime, and ceftriaxone and is a problem especially in infections due to Enterobacter aerogenes and Enterobacter cloacae, where an isolate initially susceptible to these agents may become resistant upon therapy. Transmissible plasmids have acquired genes for AmpC enzymes, which consequently can now appear in bacteria lacking or poorly expressing a chromosomal blaAmpC gene, such as Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis. Resistance due to plasmid-mediated AmpC enzymes is less common than extended-spectrum β-lactamase production in most parts of the world but may be both harder to detect and broader in spectrum. AmpC enzymes encoded by both chromosomal and plasmid genes are also evolving to hydrolyze broad-spectrum cephalosporins more efficiently. Techniques to identify AmpC β-lactamase-producing isolates are available but are still evolving and are not yet optimized for the clinical laboratory, which probably now underestimates this resistance mechanism. Carbapenems can usually be used to treat infections due to AmpC-producing bacteria, but carbapenem resistance can arise in some organisms by mutations that reduce influx (outer membrane porin loss) or enhance efflux (efflux pump activation).

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“…Cefepime, with its dipolar charge, has the advantage of penetrating bacterial outer membranes more rapidly than 3 rd generation cephalosporins, readily reaching its target and avoiding β-lactamase inactivation. Additionally, Cefepime has a reduced affinity for β-lactamases and also appears to be a poor inducer of AmpC β-lactamases (11,12 The metabolic versatility for which Pseudomonas are so renowned. It can tolerant to wide variety of physical conditions, including temperature resistant to high concentration of salt and days, weak antiseptics and many commonly used antibiotics.…”

Section: Introductionmentioning

confidence: 99%