Clinical comparative study on the activity of cefamandole in the treatment of serious staphylococcal infections caused by methicillin-susceptible and methicillin-resistant strains

Frongillo, R. F.; Donati, Luca; Federico, Giovanni; Martino, P; Moroni, M; Ortona, L; Palumbo, Maria Giovanna; Pasticci, B. M.; Pizzigallo, Eligio; Privitera, Gaetano Pierpaolo

doi:10.1128/aac.29.5.789

Cited by 31 publications

(11 citation statements)

References 12 publications

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“…35:21a, 1987) and cefuroxime have been associated with significantly fewer postoperative staphylococcal infections (11). In contrast, cefamandole has not been consistently effective against methicillin-resistant staphylococci either in experimental models of infection (6) or in clinical studies (2,4). These discrepant results may be due to differences in degrees of methicillin resistance among strains of staphylococci (7).…”

contrasting

confidence: 41%

Relationship between cefamandole and cefuroxime activity against oxacillin-resistant Staphylococcus epidermidis and oxacillin resistance phenotype

Woods

Knapp

Washington

1987

Antimicrob Agents Chemother

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The activity of cefamandole and cefuroxime against oxacillin-resistant Staphylococcus epidermidis was studied in vitro to determine whether there was any relationship between oxacillin resistance phenotypes and cephalosporin activity. Oxacillin resistance phenotypes were determined by efficiency-of-plating studies on Mueller-Hinton agar containing oxacillin, with and without NaCl, and incubated at 30 and 35°C. On the basis of MIC and MBC determinations, cefamandole was more active than cefuroxime against oxacillin-resistant S. epidermidis. Although temperature had minimal effect on the activity of either cefamandole or cefuroxime, NaCl significantly decreased the activity of cefuroxime but not of cefamandole. Neither cephalosporin consistently produced -99.9% bactericidal activity within 24 h in timed killing-curve studies. No consistent relationship was observed between cefamandole or cefuroxime activity and oxacillin resistance phenotype.According to current standards for antimicrobial susceptibility tests of the National Committee for Clinical Laboratory Standards, all methicillin-resistant staphylococci should be considered resistant to cephalosporins (8). In recent studies, however, cefamandole has been shown to be active in vitro against methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis (3, 13). Furthermore, when compared with cefazolin for prophylaxis in cardiac surgery patients, both cefamandole (M. R. Petracek, A. B. Kaiser, J. W. Lea, D. S. Kernodle, and A. C. Roach, Clin. Res. 35:21a, 1987) and cefuroxime have been associated with significantly fewer postoperative staphylococcal infections (11). In contrast, cefamandole has not been consistently effective against methicillin-resistant staphylococci either in experimental models of infection (6) or in clinical studies (2, 4). These discrepant results may be due to differences in degrees of methicillin resistance among strains of staphylococci (7). Recently Hartman and Tomasz identified three phenotypes of methicillin-resistant S. aureus: homogeneous, heterogeneous, and thermosensitive heterogeneous (5). Studies identifying phenotypes of methicillin-resistant S. epidermidis, however, have not been done. The objectives of our study were first to determine whether methicillin (oxacillin) resistance phenotypes similar to those identified for methicillin-resistant S. aureus exist among oxacillinresistant S. epidermidis and second to determine whether the resistance phenotype relates to the activity of cefamandole and cefuroxime against oxacillin-resistant S. epidermidis. MATERIALS AND METHODSOrganisms. Blood culture isolates, identified specifically as S. epidermidis, were taken from 40 patients. Each isolate was initially characterized as being oxacillin resistant by disk diffusion susceptibility testing (16). * Corresponding author. Antimicrobial agents and susceptibility testing. Oxacillin was obtained from Sigma Chemical Co., St. Louis, Mo.; cefamandole was obtained from Eli Lilly & Co., Indianapolis, Ind.; and cefuroxime was ...

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confidence: 41%

Relationship between cefamandole and cefuroxime activity against oxacillin-resistant Staphylococcus epidermidis and oxacillin resistance phenotype

Woods

Knapp

Washington

1987

Antimicrob Agents Chemother

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“…This has led to the recommendation that vancomycin be used as the agent of choice for these infections. Yet, in some studies (11) cefamandole has been found to be effective clinically for a wide range of infections (excluding endocarditis) caused by methicillin-resistant staphylococci. Our data support the results of the latter studies, although cross-resistance between methicillin and cephalosporin agents with staphylococci (1,18) …”

Section: Methodsmentioning

confidence: 99%

Activity of LY146032 compared with that of methicillin, cefazolin, cefamandole, cefuroxime, ciprofloxacin, and vancomycin against staphylococci as determined by kill-kinetic studies

Stratton¹,

Liu²,

Weeks³

1987

Antimicrob Agents Chemother

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Kill-kinetic methods were used to provide data on the bactericidal activity of subinhibitory (0.5x MIC), inhibitory (ix MIC), and suprainhibitory (4x MIC) concentrations of LY146032 against methicillinsusceptible and -resistant Staphylococcus aureus and Staphylococcus epidermidis. These bactericidal activities were compared with those of methicillin, cefazolin, cefamandole, cefuroxime, ciprofloxacin, and vancomycin. LY146032 was among the most active of the antistaphylococcal agents tested, as determined by broth microdilution methods, with all strains being inhibited at concentrations of '1 ,ug/ml. Time kill-kinetic studies demonstrated that at 4x MIC, LY146032 was rapidly bactericidal against all strains of staphylococci. Our data show that LY146032 has significant bactericidal activity against staphylococci in comparison with other antistaphylococcal agents. Further evaluation of LY146032 against serious staphylococcal infections is warranted.LY146032 is a cyclic polypeptide which has been shown by standard broth dilution techniques to be bactericidal against staphylococci at concentrations near the MIC (6-8, 14, 25). This suggests that LY146032 may be useful clinically as a single agent against serious staphylococcal infectons, including endocarditis. To provide additional data on the bactericidal activity of LY146032 in comparison with those of methicillin, cefazolin, cefamandole, cefuroxime, ciprofloxacin, and vancomycin, kill-kinetic methods were used in this study to compare the subinhibitory (0.5x MIC), inhibitory (lx MIC), and suprainhibitory (4x MIC) concentrations of these agents. MATERIALS AND METHODSMicroorganisms. One hundred isolates of staphylococci obtained from blood were studied. Included in these isolates were 25 strains of methicillin-susceptible (MIC, .2 jig/ml) S. aureus, 25 strains of methicillin-resistant (MIC, -16 ptg/ml) S. aureus, 25 strains of methicillin-susceptible (MIC, .2 ,ug/ml) S. epidermidis, and 25 strains of methicillin-resistant (MIC, .16 ,ug/ml) S. epidermidis. Identification of S. aureus was performed by a previously established methodology (13) which included colony morphology, Gram stain characteristics, ability to coagulate rabbit serum, and the presence of heat-stable DNase activity. Identification of S. epidermidis was done by using criteria and methods established by Kloos and Jorgensen (13). Methicillin-susceptible and -resistant strains were determined by a reference broth microdilution method with Mueller-Hinton broth containing 2% NaCl (20,24 ciprofloxacin, Miles Pharmaceuticals, West Haven, Conn. Antimicrobial stock solutions were prepared according to the instructions of the manufacturers and stored at -70°C until use. Final concentrations were prepared on the day they were used.Media. Mueller-Hinton broth (BBL Microbiology Systems, Cockeysville, Md.) was used in both the broth microdilution method and the kill-kinetic method and was supplemented with 2% NaCl for the testing of beta-lactam agents (20,24) and with physiologic concentrations of calcium and mag...

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“…A favorable experience with cefamandole, often in combination with other drugs, against methicillin-resistant coagulase-negative staphylococci and S. aureus has been reported (64). Many of the infections, however, were of minor or moderate severity (e.g., skin or soft-tissue infection, some of which were attributed to coagulase-negative strains, and transient bacteremia) that may have responded as a result of other interventions (e.g., removal of infected intravascular device, surgical drainage).…”

Section: Fusidic Acidmentioning

confidence: 99%

Methicillin-resistant staphylococci

1988

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Strains of staphylococci resistant to methicillin were identified immediately after introduction of this drug. Methicillin-resistant strains have unusual properties, the most notable of which is extreme variability in expression of the resistance trait. The conditions associated with this heterogeneous expression of resistance are described. Methicillin resistance is associated with production of a unique penicillin-binding protein (PBP), 2a, which is bound and inactivated only at high concentrations of beta-lactam antibiotics. PBP2a appears to be encoded by the mec determinant, which also is unique to methicillin-resistant strains. The relationships between PBP2a and expression of resistance and implications for the mechanism of resistance are discussed. The heterogeneous expression of methicillin resistance by staphylococci poses problems in the detection of resistant strains. Experience with several susceptibility test methods is reviewed and guidelines for performance of these tests are given. Treatment of infections caused by methicillin-resistant staphylococci is discussed. Vancomycin is the treatment of choice. Alternatives have been few because methicillin-resistant strains often are resistant to multiple antibiotics in addition to beta-lactam antibiotics. New agents which are active against methicillin-resistant staphylococci are becoming available, and their potential role in treatment is discussed.

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Clinical comparative study on the activity of cefamandole in the treatment of serious staphylococcal infections caused by methicillin-susceptible and methicillin-resistant strains

Cited by 31 publications

References 12 publications

Relationship between cefamandole and cefuroxime activity against oxacillin-resistant Staphylococcus epidermidis and oxacillin resistance phenotype

Relationship between cefamandole and cefuroxime activity against oxacillin-resistant Staphylococcus epidermidis and oxacillin resistance phenotype

Activity of LY146032 compared with that of methicillin, cefazolin, cefamandole, cefuroxime, ciprofloxacin, and vancomycin against staphylococci as determined by kill-kinetic studies

Methicillin-resistant staphylococci

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