Vancomycin-Tolerant Streptococcus Pneumoniae and Its Clinical Significance

Mitchell, Lauren; Tuomanen, Elaine

doi:10.1097/00006454-200105000-00012

Cited by 11 publications

(10 citation statements)

References 13 publications

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“…Tolerance was first described for ␤-lactam antibiotics, and the penicillin-tolerant phenotype was recognized in 1985 in eight clinical isolates of pneumococci (278). Tolerance to vancomycin has also been described in clinical isolates of S. pneumoniae (279)(280)(281)(282) and has been linked with treatment failure (279). While the mechanism of tolerance has not been fully elucidated, it has been suggested that tolerance is due to a faulty system of regulation of autolysins or changes in the composition of the cell wall (283).…”

Section: Antibiotic Tolerancementioning

confidence: 99%

Biological and Epidemiological Features of Antibiotic-Resistant Streptococcus pneumoniae in Pre- and Post-Conjugate Vaccine Eras: a United States Perspective

et al. 2016

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SUMMARYStreptococcus pneumoniaeinflicts a huge disease burden as the leading cause of community-acquired pneumonia and meningitis. Soon after mainstream antibiotic usage, multiresistant pneumococcal clones emerged and disseminated worldwide. Resistant clones are generated through adaptation to antibiotic pressures imposed while naturally residing within the human upper respiratory tract. Here, a huge array of related commensal streptococcal strains transfers core genomic and accessory resistance determinants to the highly transformable pneumococcus. β-Lactam resistance is the hallmark of pneumococcal adaptability, requiring multiple independent recombination events that are traceable to nonpneumococcal origins and stably perpetuated in multiresistant clonal complexes. Pneumococcal strains with elevated MICs of β-lactams are most often resistant to additional antibiotics. Basic underlying mechanisms of most pneumococcal resistances have been identified, although new insights that increase our understanding are continually provided. Although all pneumococcal infections can be successfully treated with antibiotics, the available choices are limited for some strains. Invasive pneumococcal disease data compiled during 1998 to 2013 through the population-based Active Bacterial Core surveillance program (U.S. population base of 30,600,000) demonstrate that targeting prevalent capsular serotypes with conjugate vaccines (7-valent and 13-valent vaccines implemented in 2000 and 2010, respectively) is extremely effective in reducing resistant infections. Nonetheless, resistant non-vaccine-serotype clones continue to emerge and expand.

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Section: Antibiotic Tolerancementioning

confidence: 99%

Biological and Epidemiological Features of Antibiotic-Resistant Streptococcus pneumoniae in Pre- and Post-Conjugate Vaccine Eras: a United States Perspective

et al. 2016

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“…Antimicrobial tolerance (43) is defined as the capacity of bacteria to survive, but not grow, during antibiotic therapy (22). Tolerant bacteria cease active growth and are not killed by normally lethal doses of a given antibiotic, yet the MICs for tolerant bacteria remain identical to those seen for their nontolerant counterparts.…”

mentioning

confidence: 99%

“…Tolerant bacteria cease active growth and are not killed by normally lethal doses of a given antibiotic, yet the MICs for tolerant bacteria remain identical to those seen for their nontolerant counterparts. This mechanism for persistence in the presence of antibiotics is distinct from that of antimicrobial resistance, in which bacteria are insensitive to the antibiotic and continue to multiply in the presence of the inhibitor (22). Given the insidious nature of tolerant bacteria, it is thought that replication of these organisms will renew once the drug is removed.…”

mentioning

confidence: 99%

“…As a result, vancomycin is now recommended for initial treatment of pneumococcal meningitis in children (33). Thus, the recent recovery of clinical isolates of S. pneumoniae exhibiting tolerance to vancomycin (1,10,20,22,44) is of utmost concern, as this may be indicative of selective pressure for the emergence of true vancomycin resistance in this devastating pathogen.…”

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confidence: 99%

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Vancomycin Tolerance Induced by Erythromycin but Not by Loss ofvncRS,vex3, orpep27Function inStreptococcus pneumoniae

et al. 2002

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Vancomycin-tolerant Streptococcus pneumoniae is a growing problem among drug-resistant human pathogens. Some vancomycin-tolerant pneumococci have been reported to carry mutations in loci encoding a two-component regulatory system designated VncRS or in a proximal ABC transporter, Vex. A model was advanced proposing that the tolerance phenotype resulted from the inability of a vncS mutant to respond to the Vex-transported Pep27 "death peptide" signal and dephosphorylate VncR, thereby preventing relief of repression of autolytic and other cell death functions in response to antibiotics. To explore this hypothesis, we constructed mutations in vncS, vncR, vex3, and pep27 in S. pneumoniae strain R6 and two additional genetic backgrounds. The lytic responses of the isogenic ⌬vncS, ⌬vex3, ⌬vncR, and ⌬pep27 mutants, but not a ⌬lytA strain, to vancomycin were indistinguishable from that of the parent strain. ⌬vncS strains also failed to exhibit tolerance to vancomycin at various doses in multiple media and showed wild-type sensitivity to other classes of autolysis-inducing antibiotics. In contrast, addition of subinhibitory levels of the antibiotic erythromycin led to tolerance to vancomycin during late, but not early, exponential-phase growth in a ⌬vncS strain, in the parent strain R6, and in two other strains bearing erythromycin resistance markers, namely, a ⌬vncR strain and an unrelated ⌬comD strain that is defective in competence-quorum sensing. Thus, this tolerance effect resulted from changes in cell growth or other erythromycin-dependent phenomena and not inactivation of vncS per se. Consistent with these results, and in contrast to a previous report, we found that a synthetic form of Pep27 did not elicit lytic or nonlytic killing of pneumococci. Finally, microarray transcriptional analysis and ␤-galactosidase reporter assays revealed VncS-dependent regulation of the vex123 gene cluster but did not support a role for VncRS in the regulation of autolytic or other putative cell death loci. Based on these findings, we propose that vancomycin tolerance in S. pneumoniae does not result from loss of vncS function alone.

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“…VncS is a histidine kinase that acts as the sensor of a two-component regulatory system sensing the accumulation of Pep27 and subsequently leading to activation of LytA. Vex is the transporter protein inducing the secretion of Pep27 to the extracellular compartment (14,17,18). The V440A substitution in vncS has been proposed to cause tolerance in early VTSP isolates (6).…”

Section: Discussionmentioning

confidence: 99%

Vancomycin-Tolerant Streptococcus pneumoniae in Korea

et al. 2006

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A nationwide surveillance study was undertaken to monitor antimicrobial resistance among clinical isolates of Streptococcus pneumoniae in Korea, with a special focus on vancomycin tolerance. For the 6-month period from March to August 2002, clinical isolates of S. pneumoniae were collected from 11 university hospitals and 1 reference laboratory. One-hundred eighty-eight isolates were measured for lysis rates after exposure to vancomycin for 4 h. Two vancomycin-tolerant S. pneumoniae (VTSP) strains, S3 and H8, were isolated from sputum cultures of two patients, who had stayed in intensive-care units of different hospitals with long-term antibiotic therapy and were not treated for pneumococcal pneumonia. The penicillin, cefotaxime, and vancomycin MICs for S3 were 8 g/ml, >16 g/ml, and 0.5 g/ml, and those for H8 were 2 g/ml, 2 g/ml, and 0.5 g/ml, respectively. While S3 belonged to serotype 23F and was autolysin defective, H8 belonged to serotype 13F and had intact autolysin. These strains were not clonally related as determined by pulsed-field gel electrophoresis of chromosomal DNA. In agreement with previous reports, both isolates showed pairing of TIGR4 vex2 with R6 pep27 and had two identical amino acid substitutions, Q441K in vncS and N25D in vex2. These findings indicate that two VTSP strains have emerged independently in Korea, suggesting a prevalence rate of 1.1%. The emergence of VTSP would be a serious threat in Korea, where there are significant rates of penicillin resistance in S. pneumoniae. Monitoring of the prevalence of VTSP and further investigation of the clinical relevance of VTSP are warranted.

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Vancomycin-Tolerant Streptococcus Pneumoniae and Its Clinical Significance

Cited by 11 publications

References 13 publications

Biological and Epidemiological Features of Antibiotic-Resistant Streptococcus pneumoniae in Pre- and Post-Conjugate Vaccine Eras: a United States Perspective

Biological and Epidemiological Features of Antibiotic-Resistant Streptococcus pneumoniae in Pre- and Post-Conjugate Vaccine Eras: a United States Perspective

Vancomycin Tolerance Induced by Erythromycin but Not by Loss ofvncRS,vex3, orpep27Function inStreptococcus pneumoniae

Vancomycin-Tolerant Streptococcus pneumoniae in Korea

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