Effects of the 7-valent pneumococcal conjugate vaccine on U.S. levofloxacin-resistant Streptococcus pneumoniae.
BACKGROUND
Seven-valent pneumococcal conjugate vaccine (PCV7) provides protection against invasive pneumococcal disease that extends to unvaccinated populations, such as elderly or immunocompromised adults. PCV7 also reduces incidence of pneumococcal penicillin resistance. In this study, the potential impact of PCV7 on pneumococcal fluoroquinolone resistance was examined.


METHODS
U.S. levofloxacin-resistant isolates (264) from TRUST surveillance studies (1999-2004) were serotyped and quinolone resistance-determining region of parC/E and gyrA/B sequenced. Changes in prevalence of vaccine/nonvaccine serotypes during 2000-2004 and 1999-2004 were analyzed by regression analyses and chi-square trend test.


RESULTS
The introduction of PCV7 (2000-2004) did not affect fluoroquinolone resistance prevalence, but mutants with vaccine serotypes declined linearly at -6.6 +/- 0.8% per year (p = 0.003), with concomitant replacement by nonvaccine serotypes; vaccine-related serotypes (6A, 9N, 19A, and 23N) increased (p = 0.04). Differential selection between vaccine and nonvaccine serotypes occurred for mutants containing amino acid substitutions at either ParC Ser79 (p = 0.01) or both ParC Ser79 and GyrA Ser81 (p = 0.04). Among mutants with ParC Ser79 substitutions, vaccine serotypes declined linearly (p = 0.02), whereas nonvaccine serotypes increased (p = 0.04). Additionally, a vaccine-independent effect became apparent during 1999-2004, as the incidence of ParC Ser79 and Asp83 mutations declined in fluoroquinolone-resistant strains, suggesting that these substitutions conferred decreased fitness.


CONCLUSIONS
PCV7 has led to extensive replacement of vaccine serotypes by nonvaccine serotypes among levofloxacin-resistant pneumococci.
Davies
Todd A
TA
Johnson & Johnson Pharmaceutical Research & Development, LLC, Raritan, New Jersey 08869, USA. tdavies@prdus.jnj.com
Yee
Y Cheung
YC
Bush
Karen
K
Sahm
Dan
D
Evangelista
Alan
A
Goldschmidt
Raul
R
D019943:Amino Acid Substitution; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001483:Base Sequence; D016009:Chi-Square Distribution; D027081:DNA Gyrase / Q000235:genetics; D027101:DNA Topoisomerase IV / Q000235:genetics; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D006801:Humans; D064704:Levofloxacin; D022401:Meningococcal Vaccines / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015242:Ofloxacin / Q000494:pharmacology; D011008:Pneumococcal Infections / Q000382:microbiology; D022242:Pneumococcal Vaccines / Q000494:pharmacology*; D012044:Regression Analysis; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000302:isolation & purification; D014481:United States
D000900:Anti-Bacterial Agents; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D022401:Meningococcal Vaccines; D022242:Pneumococcal Vaccines; D064704:Levofloxacin; D015242:Ofloxacin; D027101:DNA Topoisomerase IV; D027081:DNA Gyrase