beta-Lactamases are the commonest single cause of bacterial resistance to beta-lactam antibiotics. Numerous chromosomal and plasmid-mediated types are known and may be classified by their sequences or phenotypic properties. The ability of a beta-lactamase to cause resistance varies with its activity, quantity, and cellular location and, for gram-negative organisms, the permeability of the producer strain. beta-Lactamases sometimes cause obvious resistance to substrate drugs in routine tests; often, however, these enzymes reduce susceptibility without causing resistance at current, pharmacologically chosen breakpoints. This review considers the ability of the prevalent beta-lactamases to cause resistance to widely used beta-lactams, whether resistance is accurately reflected in routine tests, and the extent to which the antibiogram for an organism can be used to predict the type of beta-lactamase that it produces.

https://courses.washington.edu/pharm522/Week9/0139.pdf

beta-Lactamases in laboratory and clinical resistance.

Methicillin resistance in staphylococci is determined by mec, composed of 50 kb or more of DNA found only in methicillin-resistant strains. mec contains mecA, the gene for penicillin-binding protein 2a (PBP 2a); mecI and mecR1, regulatory genes controlling mecA expression; and numerous other elements and resistance determinants. A distinctive feature of methicillin resistance is its heterogeneous expression. Borderline resistance, a low-level type of resistance to methicillin exhibited by strains lacking mecA, is associated with modifications in native PBPs, beta-lactamase hyperproduction, or possibly a methicillinase. The resistance phenotype is influenced by numerous factors, including mec and beta-lactamase (bla) regulatory elements, fem factors, and yet to be identified chromosomal loci. The heterogeneous nature of methicillin resistance confounds susceptibility testing. Methodologies based on the detection of mecA are the most accurate. Vancomycin is the drug of choice for treatment of infection caused by methicillin-resistant strains. PBP 2a confers cross-resistance to most currently available beta-lactam antibiotics. Investigational agents that bind PBP 2a at low concentrations appear promising but have not been tested in humans. Alternatives to vancomycin are few due to the multiple drug resistances typical of methicillin-resistant staphylococci.

Methicillin resistance in staphylococci : Molecular and biochemical basis and clinical implications

STAPHYLOCOCCUS AUREUS is one of the most versatile human pathogens. In the late 1930s, sulfonamides offered the first challenge to S. aureus, but they failed because of their poor clinical performa...

Methicillin-Resistant Staphylococcus aureus

Methicillin-resistant Staphylococcus aureus: A consensus review of the microbiology, pathogenesis, and epidemiology with implications for prevention and management

These evidence-based guidelines have been produced after a literature review of the laboratory diagnosis and susceptibility testing of methicillin-resistant Staphylococcus aureus (MRSA). We have considered the detection of MRSA in screening samples and the detection of reduced susceptibility to glycopeptides in S. aureus. Recommendations are given for the identification of S. aureus and for suitable methods of susceptibility testing and screening for MRSA and for S. aureus with reduced susceptibility to glycopeptides. These guidelines indicate what tests should be used but not when the tests are applicable, as aspects of this are dealt with in guidelines on control of MRSA. There are currently several developments in screening media and molecular methods. It is likely that some of our recommendations will require modification as the new methods become available.

/pdf/guidelines-for-the-laboratory-diagnosis-and-susceptibility-4w8lx3nfeh.pdf

Guidelines for the laboratory diagnosis and susceptibility testing of methicillin-resistant Staphylococcus aureus (MRSA)

We showed that most Staphylococcus aureus strains that have borderline or intermediate susceptibility to the penicillinase-resistant penicillins (PRPs) react this way because of the activity of their beta-lactamase on these antimicrobial agents These strains produced large amounts of staphylococcal beta-lactamase that rapidly hydrolyzed penicillin and partially hydrolyzed the PRPs Susceptibility to hydrolysis was penicillin greater than oxacillin greater than cephalothin greater than methicillin The borderline results and the hydrolysis could be prevented by the beta-lactamase inhibitors clavulanic acid and sulbactam For intrinsically methicillin-resistant (heteroresistant) S aureus, the inhibitors reduced the penicillin MICs, but the strains remained resistant to all the beta-lactam antimicrobial agents, including penicillin We conclude that the borderline in vitro susceptibility or resistance to PRPs in most of these S aureus strains is mediated by beta-lactamase and they are not heteroresistant or intrinsically resistant We do not know whether this in vitro resistance is expressed clinically

C Thornsberry

Papers

The role of beta-lactamase in staphylococcal resistance to penicillinase-resistant penicillins and cephalosporins.