Novel Antibiotic-Resistant Pneumococcal Strains Recovered from the Upper Respiratory Tracts of HIV-Infected Adults and Their Children in Kisumu, Kenya

Abstract

In a survey of genetic diversity within penicillin-nonsusceptible pneumococcal isolates in Kenya, we examined 162 upper respiratory isolates from 104 human immunodeficiency virus (HIV)-infected adults and 46 children in a cotrimoxazole prophylaxis study. Antibiotic resistance levels were high; 152 (94.4%) were cotrimoxazole nonsusceptible (134 fully resistant) and 124 (77%) were intermediately penicillin resistant. Isolates nonsusceptible to penicillin and cotrimoxazole (PNCNP) were found among 24 of the 29 serotypes encountered, 15 of which have rarely or never had documented nonsusceptibility to penicillin. These included serotypes 3, 4, 7C, 7F, 10A, 11A, 13, 15A, 15B, 16F, 17F, 19B, 21, 35A, and 35B. Segments of pbp2b genes from 9 PNCNP (serotypes 3, 13, 15A, 16F, 20, and 35A) were typical of resistance-conferring alleles in that they were highly divergent and contained two substitutions thought to be critical for resistance. Similarly, the dhfr genes from 3 PNCNP were divergent and contained a substitution required for cotrimoxazole resistance. Multilocus sequence typing (MLST) of 48 PNCNP revealed 33 sequence types (STs), none of which were previously recorded at http://www.mlst.net. Comparisons with all known STs revealed that 23 of these STs were unrelated to other known STs, whereas 10 STs were highly related to STs from internationally disseminated strains, including 2 of the 26 antibiotic-resistant clones recognized by the Pneumococcal Molecular Epidemiology Network. Based upon differing serotypes expressed by strains of identical or closely similar genotypes, there has been an extensive history of capsular switching within seven genetic clusters represented by these 10 STs and related STs described at http://www.mlst.net.

Emergence of a Unique Penicillin-Resistant Streptococcus pneumoniae Serogroup 35 Strain

“…All RESIST group strains showed PFGE profiles identical to each other and to that of the resistant 35B strain identified by Beall et al, and it seems highly likely that the RESIST group strains originated from the same clone (7). Based on the results of several studies worldwide, it appears that a high proportion of PNSP SGT 35 strains, including our RESIST group strains, were derived from this clone (7,15,21,25,28,29). However, the clone that circulated in our community possessed a unique nucleotide sequence (nucleotides 1227 to 1458) that differed from any sequence published in PubMed.…”

“…PNSP strains of other SGTs have been recognized worldwide, especially serotype 35B (7,15,21,25,28,29). Between 1983 and 2005, we recovered seven SGT 35 isolates, three of which were PNSP, and other than the five common SGTs, they represented the only other PNSP SGTs in our community (30,36).…”

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

“…This observation of stable genetic changes that have occurred in the postpenicillin era reflects extremely rapid and effective adaptation to the global selection pressure exerted by ␤-lactam antibiotics. Even in some relatively remote geographic areas, one can readily isolate from healthy individuals a high proportion of nasopharyngeal pneumococcal PBP gene mutants with elevated MICs of penicillin (137)(138)(139). Even in the absence of antibiotic usage data for a given region, these observations provide direct evidence of prior ␤-lactam selection pressure in the community or in individuals (140,141) and suggest the fitness of these resultant emergent mutants in their natural reservoir.…”

Ten-Year Surveillance of Pneumococcal Infections in Temuco, Chile: Implications for Vaccination Strategies

“…The spontaneous variability in serotype isolation observed in this surveillance is of interest. Sensitive techniques like multilocus sequence typing (for follow-up of clones) will be used in the future to track these changes (22,28).…”