penicillinnonsusceptible

Penicillin nonsusceptible refers to bacteria that do not meet the susceptibility criteria for penicillin in standardized antimicrobial testing. This category includes organisms that are intermediate in susceptibility as well as those that are truly resistant, with breakpoints defined by bodies such as the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST). The term is commonly used for bacteria where penicillin and related beta-lactams are standard first-line agents, for example penicillin-nonsusceptible Streptococcus pneumoniae.

Mechanisms of nonsusceptibility vary by species. Beta-lactamase production can inactivate penicillins in many Gram-negative bacteria and some Gram-positive organisms. In Streptococcus pneumoniae and other streptococci, decreased susceptibility often results from altered penicillin-binding proteins (PBPs) that reduce drug affinity. Other factors such as changes in membrane permeability and efflux pumps can contribute, though they are less common for penicillin alone.

Testing and interpretation: Laboratories determine susceptibility using disk diffusion or broth microdilution to obtain MIC values or zone sizes. These results are interpreted as susceptible, intermediate, or resistant according to species- and drug-specific breakpoints. Breakpoints can vary by penicillin type (e.g., penicillin G, ampicillin) and by infection site, influencing clinical decisions.

Clinical implications: Penicillin nonsusceptibility can necessitate alternative therapies or higher doses, and may affect treatment of invasive diseases, pneumonia, otitis media, and meningitis. Empirical therapy often relies on local resistance patterns, with definitive therapy guided by susceptibility testing.

Examples of penicillin-nonsusceptible organisms include Streptococcus pneumoniae, Staphylococcus aureus (including beta-lactamase–producing strains), Haemophilus influenzae, Moraxella catarrhalis, and certain Gram-negative bacilli.