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

Cephalosporins have been recommended as prophylactic antibiotics in patients undergoing cardiovascular surgery. The major function of these antibiotics is to protect patients against Staphylococcus aureus and Staphylococcus epidermidis infections. The lowest inoculum amount responsible for infection during surgery is unknown but is probably low. To determine the comparative activities of cefazolin, cefuroxime, and cefamandole against S. aureus and S. epidermidis for prophylactic purposes, we selected five strains of S. aureus and S. epidermidis that presented homogeneous resistances to oxacillin. A continuously monitored turbidimetric method was used to evaluate cultures with variable inoculum sizes ranging from 106 to 1 CFU/ml and exposed to cefazolin, cefuroxime, and cefamandole at concentrations of 0.5, 1, 2, 4, 8, 16, and 32 ,ug/ml. Growth was defined as an increase of 0.1 optical density unit. The relationship between the time required for growth, the antibiotic concentration, and the initial bacterial density showed that cefamandole was more active than cefazolin, which, in turn, was revealed to be more active than cefuroxime against S. aureus and S. epidermidis.Although the benefits of antistaphylococcal prophylaxis in patients undergoing cardiac and orthopedic surgery remain uncertain, its use has become standard practice. The value of antimicrobial prophylaxis in patients undergoing cardiac surgery has never been assessed in a placebo-controlled trial, while information concerning infection rates in patients who do not receive antibiotics is scarce (1).Cephalosporins have been recommended as prophylactic antibiotics in patients undergoing cardiovascular surgery (9). The major purpose of these antibiotics is to protect patients against Staphylococcus aureus and Staphylococcus epidermidis infections. These two bacterial species are recognized as being the most important pathogens likely to infect different types of prostheses.Oxacillin-resistant strains of S. aureus and S. epidermidis may occur. Even though cephalosporins are not recommended for the treatment of infections caused by oxacillinresistant strains, it appears that these antibiotics provide effective protection early in infections caused by these bacteria (8,15).It is difficult to assess the amount of inoculum responsible for infections acquired during surgery (14). The amount is probably very low and is not comparable to the value of the inoculum used in experimental endocarditis (3).The strains included in the present study were isolated from patients with multiple positive blood cultures. They were recovered over a 3-year period, and these strains possibly may have differed in their phenotypic features.We submitted these oxacillin-resistant S. aureus and S. epidermidis strains to turbidimetric monitoring using inoculum sizes of 106 CFU/ml that were subsequently diluted 10-fold. The relative inoculum sizes (RISs) of oxacillinresistant S. aureus and oxacillin-resistant S. epidermidis were exposed to different concentrations of cefamandole, cef...

Section: Discussionmentioning

confidence: 96%

Inoculum effect on growth-delay time of oxacillin-resistant strains of Staphylococcus aureus and Staphylococcus epidermidis exposed to cefamandole, cefazolin, and cefuroxime

Yourassowsky

Linden

Crokaert

1990

“…MBCs in salt-supplemented MHB were greater than or equal to those in unsupplemented MHB. We do not know why salt supplementation resulted in such a marked change of the MBC; however, a similar effect has been observed with cefuroxime against oxacillin-resistant S. epidermidis (18). The condition.…”

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confidence: 99%

“…Because the effects of 2% NaCl and temperature on the MBCs of oxacillin against such strains had not been examined, for each strain the MCB was determined under four conditions: in MHB with and without 2% NaCl supplementation and incubation at 30 and 35°C. And given the inherent problems with the MBC test (11,12,20) and the fact that, at least with cefamandole against Staphylococcus epidermidis (18), the MBC may not accurately reflect the activity of a specific antibiotic, for selected strains we also performed time-kill rate studies under the four conditions listed above. We found that neither salt supplementation of MHB nor the temperature of incubation influenced the MIC (macrotube) of oxacillin.…”

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confidence: 99%

Bactericidal activity of oxacillin against beta-lactamase-hyperproducing Staphylococcus aureus

Woods

Yam

1988

Self Cite

The bactericidal activit of oxacilin against ,B-lactamase-hyperproducing strains of Staphylococcus aureus for which the MIC by MicroScan was 1 or 2 ,ug/ml after incubation for 24 h was evaluated by MBC studies and kill kinetics methods. MBC and kil kinetics tests were both performed using Mueler-Hinton broth (MIIB), with and without 2% NaCl supplementation, and incubation at 30 (13,14,17). The use of these detection methods has allowed identification of strains that have been classified ase-resistant penicillin. One way to approach the question of appropriate therapy in the laboratory is bactericidal testing. Therefore, we examined the bactericidal activity of oxacillin against 3-lactamase-hyperproducing strains of S. aureus by determining the MBC. Moreover, because it has been shown that the MBC may not accurately reflect the activity of an antibiotic (18), we also conducted time-kill rate studies. For all tests performed, the effects of 2% NaCl and temperature were examined.

“…In the third phenotype, the expression of resistance was also heterogeneous but was increased at 30°C in comparison with that at 37°C (10). Prior studies in our laboratory failed to demonstrate a clear-cut separation of oxacillin-resistant isolates of S. epidermidis into these three resistance phenotypes (29).The objectives of this study were, first, to determine the phenotypes of our isolates of oxacillin-resistant S. aureus and, second, to determine whether these phenotypes correlated with the activity of the cephalosporins cefamandole and cefuroxime against oxacillin-resistant S. aureus when tested at two different temperatures (30 and 35°C) and when the culture medium was supplemented or unsupplemented with NaCl. Our studies utilized oxacillin, rather than methicillin, since oxacillin is recommended for susceptibility testing of staphylococci (17) and is more stable in vitro.…”

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confidence: 99%

Characterization of resistance phenotype and cephalosporin activity in oxacillin-resistant Staphylococcus aureus

Mateos-Mora

Knapp

Washington

1988

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Forty isolates of methicillin-resistant Staphylococcus aureus were tested versus oxacillin at 30 and 35°C with and without 2% NaCl supplementation of Mueller-Hinton broth and classified as having resistance that was low (MIC,.16 ,ug/ml) or high (MIC, .32 gug/ml) and temperature or NaCl dependent. Only three isolates had low-grade resistance at both 30 and 35°C; for two isolates the MICs at 35°C were 24x the MICs at 30°C. NaCl usually increased the MICs two-to fourfold. Efficiency of plating studies were performed on strains selected for their level of oxacillin resistance and according to temperature-related difference in MICs. Most strains appeared to represent the heterogeneous resistance phenotype. Cefamandole MICs were little affected by temperature but increased with NaCl. With three exceptions, cefamandole MBCs were c4x MICs. For only six isolates were cefuroxime MICs <16 ,ug/ml. Four strains that were susceptible to both cefuroxime and cefamandole were selected for time-killing curve studies at inocula of 107 CFU/ml. At 8x MIC, cefuroxime failed to reduce the concentration of any strain by .3 x loglo CFU/ml. Killing of .3 x loglo CFU/ml was achieved by cefamandole at 4x and 8x MIC in one strain, at 8x MIC only in two strains, and by neither 4x nor 8x MIC in one strain. Within therapeutically attainable blood levels, cefuroxime is essentially inactive and cefamandole is variably bactericidal against oxacillin-resistant S. aureus.Methicillin-resistant Staphylococcus aureus should be considered resistant to P-lactam antibiotics, including all members of the cephalosporin group, according to the guidelines for antimicrobial susceptibility testing from the National Committee for Clinical Laboratory Standards (17). Some studies, however, have shown that cefamandole has good activity in vitro against both methicillin-resistant S. aureus and Staphylococcus epidermidis (7,16,20,29), although there seems to be inconsistent activity when cefamandole has been used for experimentally induced infections with methicillin-resistant S. aureus or when it has been used in clinical trials (4,6,8,11 , 1987). Discrepancies in results of treatment of staphylococcal infections with cefamandole could be due to the well-known heteroresistance found in methicillin-resistant S. aureus as well as to differences in susceptibility testing methodology, inoculum size, temperature of incubation, supplementation of culture medium with NaCl, and use of broth micro-versus macrodilution techniques (2,3,5,12,15,27).Hartman and Tomasz recently identified three different phenotypes of methicillin-resistant S. aureus: homogeneous resistance, heterogeneous resistance, and thermosensitive heterogeneous resistance (10). In the homogeneous resis-* Corresponding author. t Present address: Division of Infectious Diseases, Jackson Memorial Hospital, Miami, FL 33136. tance phenotype, methicillin resistance was expressed in approximately 100% of the cells present. In a second phenotype, the expression of resistance was heterogeneous and was not alter...