Med School Atlas

    Antimicrobial Genes

    Inappropriate prescribing predisposes patients to Clostridioides difficile.

    Resistance Mechanisms

    There are four types

    • Enzymatic alteration/deactivation of the antibiotic
    • Alteration of the antibiotic binding site
    • Alteration/closure of antibiotic entry sites
    • Antibiotic drug efflux pump

    Beta-lactamases

    Enzymes that disrupt the beta-lactam ring produced by some gram-negative bacteria. This occurs via hydrolysis.

    TEM-1/2 are plasmid mediated β-lactamases. They can be found in the following organisms:

    They are active against PCNs and Cefazolin, primarily breaking down first generation cephalosporins and all the penicillins.

    Treating for beta-lactamase resistance

    Beta-lactamases are not active against cephalosporins with an oxyimino side chain. Also consider Amoxicillin-Clavulanate. Clavulanate serves as a suicide molecule and binds to the beta-Lactamase preventing it from reaching amoxicillin.

    Some organisms have Extended Spectrum beta-Lactamases (ESBL) via the CTX-M gene, which confers resistance to the oxyimino side chain as well. If there is resistance to Ceftriaxone, assume it is an ESBL organism.

    ESBL organisms seen in hospitals

    • Klebsiella pneumoniae
    • Klebsiella oxytoca
    • Escherichia coli

    ESBLs are still susceptible to cephamycins (cefoxitin and cefotetan).

    Carbapenem Resistant Enterobacterales (CRE)

    Resistance to at least one carbapenem or the presence of a carbapenemase. They tend to have several different resistance mechanisms.

    Carbapenemase can break down the beta-lactam ring of a carbapenem. These organisms can also exhibit alterations in the outer membrane proteins, preventing attachment of antibiotics. Alterations in the Porin channels prevents the antibiotic from diffusing into membrane.

    Carbapenemases

    50% of all CRE infections in the United States are due to carbapenemases.

    Important types

    • Klebsiella pneumoniae carbapenemases (KPC)
    • New Delhi metallo-β-lactamases (NDMs)

    MecA gene

    Encodes for a low affinity penicillin binding protein 2A (PBP2A). Beta-lactam antibiotics are unable to bind to the altered PBP2A.

    The mecA gene is carried in the Staphylococcal Cassette Chromosome (SCC mec) and gets incorporated into the bacterial host's genome.

    SCC can also carry mecC, which is bovine, but can be responsible for MRSA.

    Methicillin-resistant Staphylococcus aureus (MRSA)

    This confers resistance to all beta-lactams. For more, see here: Gram Positive Cocci > Staphylococcus aureus

    Hospital acquired MRSA (HA-MRSA): Multidrug resistant (type I-3, 6, 8)
    Community acquired MRSA (CA-MRSA): Confers only beta-lactam resistance (type 4, 5, 7)

    blaZ gene

    Stands for beta-Lactamase Z. It encodes for Penicillinase production within Staphylococcus aureus.

    For more on S. Aureus, see here: Skin and Soft Tissue Infections

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