Tolerance to Vancomycin in Pneumococci: Detection with a Molecular Marker and Assessment of Clinical Impact

Abstract

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.

Quinupristin-Dalfopristin Nonsusceptibility in Pneumococci from Sickle Cell Disease Patients

“…Equally rare, Q-D nonsusceptibility was previously reported in 97 of 4,626 (2.1%) pneumococcal isolates obtained from the general population by Jones et al by using Etest for determination of susceptibility (19), although the mechanism of resistance in these strains was not discussed. Here, we report on the Q-D nonsusceptibilities of nasopharyngeal and invasive pneumococci in over 30% of SCD patients.Testing for susceptibility to Q-D, clindamycin, and erythromycin was performed in triplicate by Etest, according to the manufacturer's instructions, with 68 SCD-associated nasopharyngeal isolates (12) and 80 SCD-associated invasive isolates (1) collected between 1994 and 2002 and, for comparison, with 105 isolates from healthy peers of the infected patients (25,27). Twenty-five (37%) nasopharyngeal SCD-associated isolates and eight (10%) invasive SCD-associated isolates were found to be Q-D nonsusceptible (Etest MIC range, 1.5 to 2 g/ml); no high-level resistance was detected.…”

“…Testing for susceptibility to Q-D, clindamycin, and erythromycin was performed in triplicate by Etest, according to the manufacturer's instructions, with 68 SCD-associated nasopharyngeal isolates (12) and 80 SCD-associated invasive isolates (1) collected between 1994 and 2002 and, for comparison, with 105 isolates from healthy peers of the infected patients (25,27). Twenty-five (37%) nasopharyngeal SCD-associated isolates and eight (10%) invasive SCD-associated isolates were found to be Q-D nonsusceptible (Etest MIC range, 1.5 to 2 g/ml); no high-level resistance was detected.…”

Revising the Role of the Pneumococcalvex-vncRSLocus in Vancomycin Tolerance

“…1) (22,23). Three of the genes, vex1, vex2, and vex3, have similarity to the transmembrane and ATP-binding proteins of ABC transporters, while the fourth gene, pep 27 , was predicted to encode a peptide of 27 amino acids. The last two genes in the locus, vncR and vncS, have similarity to response regulator and histidine kinase subunits of a two-component system.…”

“…The proposed function of the proteins was to measure cell density via a quorum-sensing mechanism and to initiate autolysis. The model predicted that Pep 27 was secreted from the cell by the Vex123 transporter system and that the peptide accumulated outside of the cell. At a threshold concentration in the environment, Pep 27 was expected to activate the membrane-bound signal sensor VncS.…”

“…The model predicted that Pep 27 was secreted from the cell by the Vex123 transporter system and that the peptide accumulated outside of the cell. At a threshold concentration in the environment, Pep 27 was expected to activate the membrane-bound signal sensor VncS. The signal would then be relayed to the DNA-binding protein VncR, which was hypothesized to be a repressor of genes involved in autolysis.…”