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Updated: Feb 8, 2026

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
Published on: December 9, 2015
Pneumococcal resistance to the third-generation cephalosporins: clinical, laboratory and molecular aspects
1Department of Medical Microbiology, University of the Witwatersrand and SAIMR, P.O. Box 1038, Johannesburg 2000, South Africa.
Abstract:
Widespread use of third-generation cephalosporins appears to have selected cephalosporin-resistant pneumococci associated with the failure of these agents in the management of meningitis. Breakpoints of 0.5 mg/l for intermediate and 2 mg/l for full resistance are proposed for the treatment of pneumococcal meningitis. As no disc tests reliably identify these breakpoints, MIC or E test confirmation of third-generation cephalosporin resistance is recommended for all strains found resistant to a 1 mug oxacillin disk. Resistant strains can be selected in a single transformation event, with PBP 2X gene rearrangements conferring low level resistance and PBP 1A gene rearrangements conferring full resistance.
Insights
Widespread cephalosporin use drives resistance in pneumococci, impacting meningitis treatment. New breakpoints and MIC testing are recommended for accurate detection of resistant strains.
Area of Science:
- Microbiology
- Infectious Diseases
- Pharmacology
Background:
- Third-generation cephalosporins are crucial for treating bacterial meningitis.
- Increasing resistance in Streptococcus pneumoniae poses a therapeutic challenge.
- Previous resistance mechanisms are not fully understood in the context of cephalosporin failure.
Purpose of the Study:
- To investigate the emergence and mechanisms of third-generation cephalosporin resistance in Streptococcus pneumoniae.
- To propose new clinical breakpoints for cephalosporin resistance in pneumococcal meningitis.
- To evaluate diagnostic methods for identifying resistant strains.
Main Methods:
- Analysis of clinical isolates of Streptococcus pneumoniae.
- Determination of minimum inhibitory concentrations (MICs) for cephalosporins.
- Genetic analysis of penicillin-binding proteins (PBPs) including PBP 2X and PBP 1A.
- Evaluation of oxacillin disk diffusion tests.
Main Results:
- Widespread use of third-generation cephalosporins has selected for resistant pneumococci.
- Proposed breakpoints: 0.5 mg/l for intermediate and 2 mg/l for full resistance in pneumococcal meningitis.
- Oxacillin disk tests do not reliably detect these resistance levels.
- PBP 2X gene rearrangements confer low-level resistance; PBP 1A rearrangements confer full resistance.
Conclusions:
- Cephalosporin resistance in pneumococci necessitates revised treatment guidelines for meningitis.
- MIC or E test confirmation is crucial for strains showing initial resistance to oxacillin.
- Understanding genetic mechanisms of resistance aids in developing targeted therapies and diagnostics.
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