Activity of FCE 22101 against methicillin-resistant Staphylococcus aureus and affinity for penicillin binding proteins

Piddock, L. J. V.; Traynor, E. A.; Wise, R.

doi:10.1093/jac/23.suppl_c.59

Cited by 5 publications

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“…Of eight previous studies that utilized salt-supplemented media, four reported MICs for 90% of the strains tested of 4 ,ug/ml or less (7,8,18,24) and the remainder yielded MICs for 90% of the strains tested of >8 ,ug/ml (10,11,17,19 MICs of c4 ,ug/ml and were categorized as susceptible to imipenem by routine susceptibility testing methods. When we performed broth microdilution tests with heavy inocula, 97% of the strains appeared to be resistant to imipenem.…”

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Failure of routine susceptibility tests to detect imipenem resistance among strains of methicillin-resistant Staphylococcus aureus

Boyce

Papa

Dickenson

et al. 1991

Antimicrob Agents Chemother

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We tested 75 methicillin-resistant Staphylococcus aureus strains for susceptibility to imipenem by using disk diffusion tests and broth microdilution tests with standard and heavy inocula. Population analysis was performed on isolates that appeared to be susceptible by these methods. All of the strains contained subpopulations of cells that are phenotypically resistant to imipenem.Strains of methicillin-resistant Staphylococcus aureus are resistant to penicillinase-resistant penicillins and cephalosporins (15), but there is continuing controversy regarding their level of susceptibility to imipenem. In a number of studies, most of the strains tested were susceptible to imipenem, with the MICs for 90% of the strains tested ranging from <1.0 to 6.25 ,ug/ml (3, 4, 6-9, 12-14, 18, 23-25). However, other investigators have reported that imipenem has variable in vitro activity against methicillin-resistant S. aureus and that MICs range from 0.1 to >64 ,ug/ml (5,10,17,19,20,22). The disparity between the results of previous studies is probably due to differences in the susceptibility testing methods used and differences in the phenotypic characteristics of the strains included. Many previous studies did not use currently recommended susceptibility testing methods (15,16,21). Moreover, some studies included isolates from only one hospital (5,6,9,13,14,20,23,24) while others failed to state how many hospitals or geographic areas were represented by the strains tested (4,8,17,19,22,25). To study this issue further, we tested a large number of strains from diverse geographic regions by using recommended susceptibility testing methods. In addition, isolates were tested by using heavy inocula, and population analysis was performed on isolates for which the imipenem MICs were low. The results revealed that all of the methicillinresistant S. aureus strains tested contained subpopulations of cells that were resistant to imipenem.(These data were previously presented at the 30th Population analysis. Two study strains (NY-A-500-1 and PMH-1424) that appeared to be susceptible to imipenem by susceptibility tests were analyzed by population analysis methods. Three methicillin-resistant S. aureus control strains (MUSC-499, NYC-1281, and ATL-1707) were included. These strains have been characterized as homogeneously resistant or heterogeneously resistant (HET-1 or HET-2) on the basis of previously described methods (1). By using these same methods, the two study strains included in the population analysis were categorized as HET-2 strains, which produce greater zones of inhibition around methicillin, oxacillin, and nafcillin disks (1). S. aureus ATCC-29213 (methicillin and imipenem susceptible) was also included.Population analysis was done by using efficiency-of-plating methods. Briefly, colonies from a 24-h agar plate were used to prepare a suspension of 109 CFU/ml. Several dilutions were made, and a spiral plater (Spiral System Instruments, Bethesda, Md.) was used to inoculate aliquots onto Mueller-Hinton agar plates containing 2% N...

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confidence: 99%

Failure of routine susceptibility tests to detect imipenem resistance among strains of methicillin-resistant Staphylococcus aureus

Boyce

Papa

Dickenson

et al. 1991

Antimicrob Agents Chemother

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“…All strains were examined in a whole-cell assay on at least two separate occasions essentially as described by Reynolds and Brown (3) and Piddock et al (13). A PBP competition assay was performed between cefpirome (± 10 mg/l clavulanic acid) and 3H-benzyl penicillin.…”

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confidence: 99%

Activity of cefpirome combined with beta-lactamase inhibitors and affinity for the penicillin-binding proteins of methicillin-resistantStaphylococcus aureus

Piddock

Traynor

Griggs

1992

Eur. J. Clin. Microbiol. Infect. Dis.

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The susceptibility of 47 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA) to cefpirome, ceftazidime and methicillin was determined with Isosensitest media, with/without 5% NaCl and incubation at 30 degrees, 37 degrees and 44 degrees C for 24 and 48 h. At 24 h the MIC50 of cefpirome was 8 mg/l compared to 64 mg/l ceftazidime; at 48 h this increased to 32 mg/l cefpirome. The addition of 10 mg/l clavulanic acid or sulbactam lowered the MIC of cefpirome (at 48 h) by greater than four-fold in 23% and 11% of the strains, respectively. Cefpirome had primary affinity for penicillin-binding protein (PBP) 1 and 2 in five MRSA and one methicillin-susceptible Staphylococcus aureus. PBP 2a was present in all MRSA and was not saturated by 64 mg/l cefpirome. Clavulanic acid at a concentration of 10 mg/l bound to PBP 2 by greater than 50% in all strains, and when combined with cefpirome, the density of PBP 2a was also reduced but not completely abolished. The data from this study suggests that the mechanism of synergy of a beta-lactamase inhibitor plus a cephalosporin for MRSA may be due to an additive effect against PBPs and not just inhibition of a beta-lactamase. No cefpirome-resistant mutants could be selected from a methicillin-susceptible Staphylococcus aureus, but mutants were selected from an MRSA (expressing homogeneous methicillin resistance) for which MICs of cefpirome were 8 to 32 mg/l.

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“…Exceptions are vancomycin and other glycopeptides (1,4,5). Of the beta-lactam antibiotics, only the carbapenems have shown some, although limited, activity against MRSA and MRCoNS, and no bactericidal activity has been demonstrated (3,6).…”

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Comparative antibacterial activity of L-695,256, a carbapenem active against methicillin-resistant staphylococci

Rylander

Rollof

Jacobsson

et al. 1995

Antimicrob Agents Chemother

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The activity of a new prototype carbapenem, L-695,256, against clinical isolates of gram-positive and gram-negative aerobes was studied in vitro by agar dilution. L-695,256 was highly active against methicillinresistant and -susceptible isolates of staphylococci (MICs, 0.016 to 2 g/ml) and against penicillin-resistant pneumococci (MICs, 0.016 to 0.064 g/ml), irrespective of penicillin susceptibility. Activity against members of the family Enterobacteriaceae was less than that of imipenem, while Proteus mirabilis and Morganella morganii were more susceptible to L-695,256.

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Activity of FCE 22101 against methicillin-resistant Staphylococcus aureus and affinity for penicillin binding proteins

Cited by 5 publications

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Failure of routine susceptibility tests to detect imipenem resistance among strains of methicillin-resistant Staphylococcus aureus

Failure of routine susceptibility tests to detect imipenem resistance among strains of methicillin-resistant Staphylococcus aureus

Activity of cefpirome combined with beta-lactamase inhibitors and affinity for the penicillin-binding proteins of methicillin-resistantStaphylococcus aureus

Comparative antibacterial activity of L-695,256, a carbapenem active against methicillin-resistant staphylococci

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