Tolerance to vancomycin in pneumococci: detection with a molecular marker and assessment of clinical impact.
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.
Rodriguez
Carina A
CA
Department of Infectious Diseases , St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Atkinson
Robyn
R
Bitar
Wally
W
Whitney
Cynthia G
CG
Edwards
Kathryn M
KM
Mitchell
Lauren
L
Li
Juan
J
Sublett
Jack
J
Li
Chin-Shang
CS
Liu
Tiebin
T
Chesney
P Joan
PJ
Tuomanen
Elaine I
EI
D000483:Alleles; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002353:Carrier State / Q000382:microbiology*; D002648:Child; D004351:Drug Resistance / Q000235:genetics*; D005260:Female; D005798:Genes, Bacterial; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008581:Meningitis / Q000188:drug therapy / Q000382:microbiology* / Q000401:mortality; D009238:N-Acetylmuramoyl-L-alanine Amidase / Q000235:genetics; D009305:Nasopharynx / Q000382:microbiology; D020641:Polymorphism, Single Nucleotide; D011494:Protein Kinases / Q000235:genetics; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D016019:Survival Analysis; D014640:Vancomycin / Q000494:pharmacology* / Q000627:therapeutic use
D000900:Anti-Bacterial Agents; D005819:Genetic Markers; D014640:Vancomycin; D011494:Protein Kinases; C119671:VncS histidine kinase; D009238:N-Acetylmuramoyl-L-alanine Amidase