Fourth-Generation Cephalosporins: In vitro Activity against Nosocomial Gram-Negative Bacilli Compared with β-Lactam Antibiotics and Ciprofloxacin

Abstract

The in vitro activity of two new expanded spectrum fourth-generation cephalosporins, cefepime and cefpirome, was compared with that of five antibacterial agents, ceftazidime, cefoperazone, cefotaxime, imipenem, and ciprofloxacin, that are commonly used in the treatment of serious infections caused by aerobic gram-negative bacteria. The agar dilution method described by the US National Committee for Clinical Laboratory Standards was used to determine the minimum inhibitory concentrations of antibiotics tested. Three hundred and two clinical isolates, representing a cross-section of Klebsiella and Enterobacter species and Pseudomonas aeruginosa were tested. The most potent β-lactams were imipenem, cefepime, and cefpirome, which demonstrated significant activity against the majority of strains in all three genera of bacteria, as did ciprofloxacin. Ceftazidime was active against P. aeruginosa, but was less potent against Klebsiella and Enterobacter species. Cefoperazone and cefotaxime were less active than ceftazidime against P. aeruginosa. Cefepime had slightly greater activity than cefpirome against the gram-negative bacteria tested. These data indicate that cefepime and cefpirome are highly active against many frequently resistant nosocomial bacterial strains that are traditionally responsible for difficult-to-treat infections.

Cefepime versus ceftazidime: considerations for empirical use in critically ill patients

“…Literature exists that supports this, with some papers reporting bacterial resistance to, or reduced efficacy of, ceftazidime compared with cefepime [38,[53][54][55][56]. Tumah [55] compared the in vitro activity of various ␤-lactam antibiotics in 302 clinical isolates of Klebsiella, Enterobacter spp. and Pseudomonas aeruginosa.…”

In vitro AN69 and Polysulphone Membrane Permeability to Ceftazidime and in vivo Pharmacokinetics during Continuous Renal Replacement Therapies

“…There are some clinical data on the removal of ceftazidime by CRRT [2,[11][12][13][14][15] , but it is difficult to compare data from different forms of CRRT because the mechanism of drug removal in hemofiltration (i.e., drug removal by convection) differs from that of hemodiafiltration (i.e., removal by convection plus diffusion) [16] . There are also differences in flow rates, dose regimens and membranes used in the studies mentioned above.…”

Development and Validation of Uv Spectrophotometry and Liquid Chromatography Methods for Determination of Cefpirome in Raw Material and Pharmaceutical Dosage

“…It is considered to be highly active against both gram-negative organisms including Pseudomonas aeruginosa and gram-positive organisms including staphylococci. It is stable to both plasmid and chromosomal βlactamases and has been shown to induce less class I βlactamase resistance than other cephalosporins (2,(5)(6)(7). The increased spectrum of activity, together with high stability against -lactamases and rapid transmembrane transport, distinguishes cefpirome as an example of a fourthgeneration cephalosporin and its principal use is in treatment for patients' septic shock or several sepsis (2,(5)(6)(7)(8)(9)(10).…”

“…Methods have been reported for the determination of cefpirome in plasma, serum, urine, tissue, raw material and pharmaceutical form. These methods include microbiological assay, HPLC, voltammetry assay, UV spectrometry and pH potentiometry (2,(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). The aim of this study was to develop and validate simple and rapid UV Spectrophotometry and Liquid Chromatography (HPLC) methods for the quantification of cefpirome in raw material and powder for injectable preparation.…”

“…The high purity value indicates that the chromatographic method has specificity against the likely degradation products. 2 Chromatographer Schimadzu LC-10A, with SPD-10A variablewavelength detector (set at 265 nm), an SCL-10A system controller, a LC 10 AS pump, a C-R6A integrator and Rheodyne injection valve with 20 µL loop (Shimadzu, Kyoto, Japan) 3 ACE HPLC Column C18 (5 µ, 250 mm x 4 mm) (Nova Analitica, São Paulo, Brazil) 4 Methanol Tedia (Tedia Brazil, Rio de Janeiro, Brazil) 5 Statistic analyze by Student's t-test demonstrated no significant difference between the two parameters (p = 0.01), Robustness is defined as a measure of capability of the method to remain unaffected by small, but deliberate variations in method parameters. The Tables 7 and 8 shows that the solutions assayed in robustness test exhibited no concentration changes of cefpirome.…”