Laboratory assessment of antibacterial activity of zwitterionic 7-methoxyimino cephalosporins

Péchère, Jean-Claude; Wilson, Walter Walter; Neu, H C

doi:10.1093/jac/36.5.757

Cited by 22 publications

(18 citation statements)

References 43 publications

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“…Like all 7-methoxyimino cephalosporins, cefepime is a zwitterion maintaining a net neutral charge at pH ranges encountered in vivo. The presence of a positively charged region in the structure of these antibiotics may enhance their penetration [10], and this property may have played a role in the intravitreal penetration of cefepime after intravenous injection in noninflamed phakic human eyes.…”

Section: Discussionmentioning

confidence: 99%

Intravitreal Penetration of Cefepime after Systemic Administration to Humans

Aras

Özdamar²,

Öztürk³

et al. 2002

Ophthalmologica

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Purpose: To investigate the penetration of cefepime (a fourth-generation cephalosporin) into the vitreous after single-dose intravenous administration to human subjects. Methods: Thirty phakic patients about to undergo vitreous surgery received 1 g (group 1, 15 patients) or 2 g cefepime (group 2, 15 patients) in a single intravenous injection before surgery. The indications for vitreous surgery were retinal detachment with proliferative vitreoretinopathy (24 patients), retinal detachment associated with giant retinal tear (4 patients), macular hole (1 patient) and intraocular foreign body (1 patient). Samples of vitreous and serum were obtained at 0.5, 1, 2, 4 and 12 h after injection. Three patients were used for each sampling time and for 1 g and 2 g of cefepime. Samples were assayed for cefepime concentrations with high-performance liquid chromatography (HPLC). Results: All the patients had detectable cefepime in their vitreous and serum measurable by HPLC. The level of cefepime in the vitreous peaked at 2 h and reached a minimum at 12 h after intravenous injection in both groups. A mean peak vitreous level of cefepime was 1.91 ± 0.13 µg/ml in group 1 and 2.86 ± 0.37 µg/ml in group 2. The level of cefepime in the vitreous at 12 h after injection was 0.89 ± 0.14 µg/ml in group 1 and 0.97 ± 0.30 µg/ml in group 2. Conclusion: The vitreous level of cefepime after intravenous injection was below the minimum inhibitory concentration (MIC₉₀) against Staphylococcus aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa, but was over the MIC₉₀ against Proteus mirabilis, Klebsiella spp., Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus pyogenes and Enterobacter spp.

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Section: Discussionmentioning

confidence: 99%

Intravitreal Penetration of Cefepime after Systemic Administration to Humans

Aras

Özdamar²,

Öztürk³

et al. 2002

Ophthalmologica

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“…All the C‐3′ quaternary compounds introduced for clinical use or under development possess the same antibacterial activity as cefotaxime, but they differ by adding antipseudomonal activity 17,18. There are differences, however, among these compounds: cefclidin is twice as active as ceftazidime against P. aeruginosa , but cefepime and cefpirome are two‐fold less active than ceftazidime against P. aeruginosa (Figure 4).…”

Section: Novelties In Antibacterial Activitiesmentioning

confidence: 99%

“…Studies have shown that cefpirome generates significant β‐lactamase induction less frequently than ceftazidime against E. cloacae. Cefpirome has been shown to select derepressed mutants in vitro and in vivo to a lesser extent than ceftazidime 17.…”

Section: Novelties In Antibacterial Activitiesmentioning

confidence: 99%

New concepts in the field of cephalosporins: C-3' quaternary ammonium cephems (Group IV)

Bryskier¹

1997

Clinical Microbiology and Infection

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The C-3' quaternary ammonium cephems belong to group IV of the microbiological classification of cephalosporins. This group is divided into two subgroups according to the position of the quaternary ammonium moiety (C-3 or C-7). These compounds are structurally related to the third-generation cephalosporins (or group 111 of the microbiological classification), but in addition are featured with two or more of the following properties: broad-spectrum activity including Pseudomonas aeruginosa; activity against Enterobacteriaceae producing type 1 p-lactamase; the presence of a quaternary moiety. The zwitterionic properties of the C-3' quaternary cephalosporins allow rapid penetration through the outer membrane of Gram-negative bacteria, stability to and low affinity for type 1 j3-lactamases in the periplasmic space and high affinity for the penicillin binding proteins (PBPs). Among the currently available analogues cefpirome and cefozopran exhibit a well-balanced antibacterial spectrum against Gram-negative bacilli and Gram-positive cocci. Cefepime is less active against Staphylococcus aureus.

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“…The plasmid‐mediated broad‐spectrum β‐lactamases found in Escherichia coli and Klebsiella pneumoniae confer resistance to the first‐generation cephalosporins 5. The third‐generation cephalosporins were introduced in the early 1980 s and were poorly hydrolyzed by these enzymes, but Gram‐negative microorganisms resistant to these compounds have emerged 6,7.…”

Section: Introductionmentioning

confidence: 99%

Fourth-generation cephalosporins: a review of in vitro activity, pharmacokinetics, pharmacodynamics and clinical utility

Garau

Wilson

Wood

et al. 1997

Clinical Microbiology and Infection

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Antimicrobial resistance to antibiotics is a significant problem in the treatment of serious nosocomial infections. Antibiotic therapy is often empiric, until a specific pathogen and its antibiotic susceptibility are known, after which time adjustments in initial therapy may be made as necessary. The increasing prevalence of Gram‐positive bacteria as a cause of serious nosocomial infections, together with the increasing incidence of resistance among Gram‐negative bacilli, require the use of compounds with broad‐spectrum antimicrobial activity. The third‐generation cephalosporins are widely used for empiric therapy but their effectiveness has been limited by the increasing prevalence of strains of Enterobacteriaceae and Pseudomonas spp. that produce derepressed AmpC β‐lactamases. The fourth‐generation cephalosporins are structurally related to the third‐generation cephalosporins but, in addition, they possess a quaternary ammonium group at the C‐3′ position. They are zwitterionic compounds, which facilitates rapid penetration through the outer membrane of Gram‐negative bacteria. This, together with their low affinity for clinically important β‐lactamases, results in potent activity against many Gram‐negative pathogens, including strains producing derepressed class I (AmpC) β‐lactamase, resistant to most third‐generation cephalosporins. In addition, some fourth‐generation cephalosporins exhibit excellent activity in vitro against Gram‐positive bacteria, including methicillin‐susceptible staphylococci, penicillin‐resistant pneumococci and viridans group streptococci. Among the fourth‐generation cephalosporins, only cefpirome and cefepime are widely available. A review of clinical studies published to date indicates that they are potentially useful as a first line empiric therapy for serious infections, including severe community‐acquired and nosocomial pneumonia, bacteremia, febrile episodes in neutropenic patients and meningitis.

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Laboratory assessment of antibacterial activity of zwitterionic 7-methoxyimino cephalosporins

Cited by 22 publications

References 43 publications

Intravitreal Penetration of Cefepime after Systemic Administration to Humans

Intravitreal Penetration of Cefepime after Systemic Administration to Humans

New concepts in the field of cephalosporins: C-3' quaternary ammonium cephems (Group IV)

Fourth-generation cephalosporins: a review of in vitro activity, pharmacokinetics, pharmacodynamics and clinical utility

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