Tolerance to vancomycin in pneumococci: detection with a molecular marker and assessment of clinical impact.

Abstract

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.

• Authors: Carina A Rodriguez, Robyn Atkinson, Wally Bitar, Cynthia G Whitney, Kathryn M Edwards, Lauren Mitchell, Juan Li, Jack Sublett, Chin-Shang Li, Tiebin Liu, P Joan Chesney, Elaine I Tuomanen
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 190 Issue 8 Pg. 1481-7 (Oct 15 2004) ISSN: 0022-1899 [Print] United States
• PMID: 15378442 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
• Copyright: Copyright 2004 Infectious Diseases Society of America

Chemical References

• Anti-Bacterial Agents
• Genetic Markers
• Vancomycin
• Protein Kinases
• VncS histidine kinase
• N-Acetylmuramoyl-L-alanine Amidase

Topics

• Alleles
• Anti-Bacterial Agents (pharmacology, therapeutic use)
• Carrier State (microbiology)
• Child
• Drug Resistance (genetics)
• Female
• Genes, Bacterial
• Genetic Markers
• Humans
• Male
• Meningitis (drug therapy, microbiology, mortality)
• N-Acetylmuramoyl-L-alanine Amidase (genetics)
• Nasopharynx (microbiology)
• Polymorphism, Single Nucleotide
• Protein Kinases (genetics)
• Streptococcus pneumoniae (drug effects, genetics, isolation & purification)
• Survival Analysis
• Vancomycin (pharmacology, therapeutic use)