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Tolerance to vancomycin in pneumococci: detection with a molecular marker and assessment of clinical impact
Carina A Rodriguez1, Robyn Atkinson, Wally Bitar
1Department of Infectious Diseases , St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Background:
Vancomycin is often added to therapy for meningitis caused by Streptococcus pneumoniae. Tolerant bacteria without classic resistance that escape killing by multiple antibiotics have been reported sporadically. We determined the prevalence of tolerance to vancomycin in pneumococci and its effect on the outcome of meningitis.
Methods:
Archival samples of 215 nasopharyngeal (NP) and 113 meningitis isolates were tested for the killing efficacy of vancomycin. Specific DNA sequence changes in a transporter locus were identified for tolerant isolates. Similar tests were conducted prospectively on 517 NP isolates from healthy children.
Results:
In archival isolates, tolerance to vancomycin was detected in 3.7% of NP and 10.6% of invasive isolates. Patients with meningitis caused by tolerant isolates had a worse estimated 30-day survival than did patients with meningitis caused by nontolerant isolates (49% vs. 86%; P = .048); 62.5% of tolerant archival NP isolates harbored a specific sequence change for pep27 and vex2 (P = .021). Prospective analysis of 517 carriage isolates indicated that 8.1% were tolerant to vancomycin and that 82.1% of tolerant isolates harbored the specified marker gene sequences (P = .001).
Conclusions:
Tolerance to vancomycin exists in the population of pneumococci. Tolerant isolates are associated with meningitis of increased mortality, and these isolates can be tracked by specific marker sequences in 2 genes.
Insights
Vancomycin tolerance in Streptococcus pneumoniae is linked to higher meningitis mortality. Specific genetic markers in pep27 and vex2 genes can identify these tolerant bacteria.
Area of Science:
- Microbiology
- Infectious Diseases
- Genetics
Background:
- Vancomycin is a critical antibiotic for treating Streptococcus pneumoniae meningitis.
- Bacterial tolerance, distinct from resistance, allows pathogens to survive antibiotic exposure.
- The prevalence and clinical impact of vancomycin tolerance in pneumococci were previously unknown.
Purpose of the Study:
- To determine the prevalence of vancomycin tolerance in Streptococcus pneumoniae.
- To investigate the association between vancomycin tolerance and meningitis outcomes.
- To identify genetic markers for tracking tolerant pneumococcal isolates.
Main Methods:
- Vancomycin killing efficacy was tested on archival and prospective nasopharyngeal and meningitis isolates.
- DNA sequencing identified specific genetic changes in tolerant isolates.
- Prospective analysis correlated genetic markers with tolerance in carriage isolates.
Main Results:
- Vancomycin tolerance was found in 3.7% of nasopharyngeal and 10.6% of meningitis isolates.
- Meningitis patients infected with tolerant strains had significantly lower survival rates (49% vs. 86%).
- Specific sequence changes in pep27 and vex2 genes were strongly associated with vancomycin tolerance.
Conclusions:
- Vancomycin tolerance is present in the pneumococcal population.
- Tolerant pneumococcal isolates are associated with increased mortality in meningitis.
- Specific genetic markers in pep27 and vex2 genes can be used to identify tolerant isolates.
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