Dynamics of pneumococcal carriage among day-care center attendees during the transition from the 7-valent to the higher-valent pneumococcal conjugate vaccines in Greece.

BACKGROUND: In Greece recently, higher-valent pneumococcal conjugate vaccines (PCVs) replaced the 7-valent (PCV7); the 10-valent (PCV10) became available in May 2009 and the 13-valent (PCV13) in June 2010. METHODS: We investigated the nasopharyngeal colonization with Streptococcus pneumoniae in day-care center attendees in Athens and the prefecture of Viotia. Between December 2010 and June 2011, nasopharyngeal cultures were obtained 4 times, at enrollment and then every 6 to 8 weeks. RESULTS: Among the 233 children, 225 (96.6%) had been vaccinated with ≥1 dose of PCV7. One tenth of the PCV7 vaccinated attendees had also received ≥1 dose of PCV13 or PCV10. During the 4 samplings, 358 isolates were recovered from a total of 874 samples. Of the 233 children, 183 (78.5%) were found to carry S. pneumoniae at least once. The overall serotype distribution among carriers was similar regardless of the time lapsed since the last PCV7 dose. A high frequency of 19A (17.1%) coincided with a low frequency of 19F (1.4%). Non-PCV13 serotypes accounted for 73.1% of the isolates; 23B, 15B/C, 16F, 21, 11A, 15A, 6C, 10A, 22F and 23A were the most common. Among attendees aged 24-59 months (median age 42 months), prolonged carriage of a non-PCV13 serotype was relatively common, mainly for 21 and 16F. One out of 4 cases of colonization with the prevalent non-PCV13 serotypes was followed by persistent carriage for 5 to 14 weeks. CONCLUSIONS: During this period of transition to the higher-valent PCVs in the day-care center setting, non-PCV13 serotypes dominated and exhibited prolonged colonization. The frequency and the duration of prolonged carriage tends to be increased, if sampling frequency increases and the carriage time before and after positive cultures is taken into consideration. Further studies regarding the fitness of the colonizing non-PCV13 serotypes will likely to be seen in the future.

Seven-year surveillance of emm types of pediatric Group A streptococcal pharyngitis isolates in Western Greece.

BACKGROUND: An experimental 26-valent M protein Group A streptococcal (GAS) vaccine has entered clinical studies. Pharyngeal GAS emm type surveillances in different areas and time-periods enhance the understanding of the epidemiology of GAS pharyngitis. Moreover, these surveillances, combined with the data on GAS invasive disease, can play a significant role in the formulation of multivalent type-specific vaccines. METHODS: During a 7-year period (1999-2005), 2408 GAS isolates were recovered from consecutive children with pharyngitis in Western Greece. The overall macrolide resistance rate was 22.8%. Along the study period we noted a tendency towards significantly decreased rates of resistance, with the lowest rates occurring in 2002 (15.3%), 2003 (15%) and 2004 (16.7%). A random sample of isolates from each year, 338 (61.7%) of the 548 macrolide-resistant and 205 (11%) of the macrolide-susceptible, underwent molecular analysis, including emm typing. RESULTS: The 543 typed isolates had 28 different emm types. A statistically significant association was found between macrolide resistance and emm4, emm22 and emm77, whereas emm1, emm3, emm6, emm12, emm87 and emm89 were associated with macrolide susceptibility. A significant yearly fluctuation was observed in emm4, emm28 and emm77. The most common macrolide-resistant GAS were emm77 isolates harboring erm(A), either alone or in combination with mef(A), emm4 carrying mef(A), emm28 possessing erm(B), emm75 carrying mef(A), emm12 harboring mef(A) and emm22 carrying erm(A). We estimated that 82.8% of the isolates belonged to emm types included in the novel 26-valent M protein vaccine. The vaccine coverage rate was determined mainly by the increased frequency of nonvaccine emm4 isolates. CONCLUSIONS: A limited number of emm types dominated among macrolide-susceptible and macrolide-resistant GAS isolates. We observed seasonal fluctuations, which were significant for emm4, emm28 and emm77. This type of data can serve as baseline information if the novel 26-valent M protein GAS vaccine is introduced into practice.

Macrolide resistance determinants among Streptococcus pneumoniae isolates from carriers in Central Greece.

BACKGROUND: We sought to characterize the temporal trends in nasopharyngeal carriage of macrolide-resistant pneumococci during a period with increased heptavalent pneumococcal conjugate vaccine (PCV7) coverage in Central Greece. METHODS: Streptococcus pneumoniae isolates were recovered from 2649 nasopharyngeal samples obtained from day-care center attendees in Central Greece during 2005-2009. A phenotypic and genotypic analysis of the isolates was performed, including the identification of macrolide resistance genes mef(A), subclasses mef(A) and mef(E), as well as erm(B). RESULTS: Of the 1105 typeable S. pneumoniae isolates, 265 (24%) were macrolide-resistant; 22% in 2005, 33.3% in 2006, 23.7% in 2007, and 20.5% in 2009 (P=0.398). Among these macrolide-resistant pneumococci, 28.5% possessed erm(B), 24.3% erm(B)+mef(E), 41.8% mef(E), and 5.3% mef(A). A mef gene as the sole resistance determinant was carried by 31% of macrolide-resistant isolates belonging to PCV7 serotypes and 75.8% of the non-PCV7 serotypes. Across the 4 annual surveillances, pneumococci carrying mef(A) gradually disappeared, whereas serotype 19F isolates carrying both erm(B) and mef(E) persisted without significant yearly fluctuations. Among isolates belonging to non-PCV7 serotypes, macrolide-resistance was observed in those of serotypes 6A, 19A, 10A, 15A, 15B/C, 35F, 35A, and 24F. In 2009, ie 5 years after the introduction of PCV7 in our country, 59% of macrolide-resistant pneumococci belonged to non-PCV7 serotypes. CONCLUSIONS: Across the study period, the annual frequency of macrolide-resistant isolates did not change significantly, but in 2009 a marked shift to non-PCV7 serotypes occurred. Overall, more than half of the macrolide-resistant isolates possessed erm(B) either alone or in combination with mef(E). erm(B) dominated among isolates belonging to PCV7 serotypes, but not among those of non-PCV7 serotypes.

Dynamics of Streptococcus pneumoniae nasopharyngeal carriage with high heptavalent pneumococcal conjugate vaccine coverage in Central Greece.

In order to study whether the use of the heptavalent pneumococcal conjugate vaccine (PCV7) led to a shift in the Streptococcus pneumoniae serotypes distribution and whether it modified the resistance to antibiotics, 2649 nasopharyngeal samples were obtained between 2005 and 2009, from children attending day-care centers in Central Greece. The percentage of attendees vaccinated with ≥1 dose of PCV7 increased from 12.9% (2005) to 95.5% (2009). Non-PCV7 serotypes replaced those belonging to PCV7. In 2009, 19F was virtually the only PCV7 serotype that continued to circulate. A significant increase in the frequency of penicillin-intermediate (oral penicillin V breakpoints) isolates coincided with a marked reduction in isolates with high resistance to penicillin. Several non-PCV7 serotypes colonized the children, but their frequency varied substantially from year to year. Each one of 14 specific non-PCV7 serotypes, i.e. 6A, 11A, 15B, 23A, 10A, 16F, 38, 22F, 15C, 19A, 35F, 24F, 6C, and 7F, accounted for ≥2% of pneumococcal isolates in at least 2 annual surveillances. An increase in non-PCV7 serotypes with antibiotic resistance, beyond 6A and 19A, occurred. Intermediate resistance to penicillin was observed in serotype 23B, 15B, 15C, 15A, 35F, 6C, and 24F pneumococci. Their exact role in invasive and non-invasive disease remains to be seen in the years ahead.

Interaction of the heptavalent pneumococcal conjugate vaccine and the use of individual antibiotics among children on nasopharyngeal colonization with erythromycin-resistant Streptococcus pneumoniae.

The purpose of this study was to assess the complex interaction of the heptavalent pneumococcal conjugate vaccine (PCV7) and individual classes of antimicrobial agents on the nasopharyngeal carriage of erythromycin-resistant pneumococci within the day-care center population. Between February 2005 and May 2007, nasopharyngeal cultures for Streptococcus pneumoniae were obtained from 1,829 day-care center attendees in Central Greece. Thirty-one percent of the pneumococci were erythromycin-resistant; 85.2% of these isolates were also penicillin-nonsusceptible. PCV7 immunization was associated with decreased carriage of erythromycin-resistant PCV7 serotypes but not with an overall decrease in erythromycin-resistant S. pneumoniae colonization. The largest decline in the carriage of erythromycin-resistant pneumococci, particularly of PCV7 serotypes, was observed among vaccinated attendees who had not been exposed to antimicrobials within the preceding 3 months. Exposure to macrolides, 90% clarithromycin, significantly correlated with erythromycin resistance (adjusted odds ratio [AOR] = 2.08, 95% confidence interval [CI] = 1.38-3.12). There was a trend toward an association between the use of oral cephalosporins, other than cefprozil and cefaclor, and colonization with erythromycin-resistant pneumococci (AOR = 1.91, 95% CI = 0.92-3.96). Penicillins had a nonsignificant correlation with the carriage of erythromycin-resistant pneumococci (AOR = 1.17, 95% CI = 0.80-1.71). Despite the widespread PCV7 immunization, the antibiotic pressure, particularly of macrolides, continues to cause dissemination of erythromycin-resistant, commonly multidrug-resistant, pneumococci within the day-care center population.

Impact of heptavalent pneumococcal conjugate vaccine on nasopharyngeal carriage of penicillin-resistant Streptococcus pneumoniae among day-care center attendees in central Greece.

BACKGROUND: In Greece, the heptavalent pneumococcal conjugate vaccine (PCV7) became available in October 2004 and it was incorporated into the national immunization schedule in January 2006. METHODS: In February 2005, a yearly surveillance of the nasopharyngeal colonization with Streptococcus pneumoniae in children attending day-care centers in Central Greece began. RESULTS: Between February 2005 and May 2007, nasopharyngeal cultures were obtained from 1829 children aged 13-76 months (median age, 47 months). The proportion of attendees vaccinated with > or =1 doses of PCV7 increased from 13% (2005) to 33% (2006) and to 70% (2007); 98% had been immunized on toddler catch-up schedules. Among vaccinated carriers, the proportion of PCV7 serotypes decreased from 33% (2005) to 29% (2006) and to 8.6% (2007) (chi for trend, P < 0.001), the proportion of PCV7-related serotypes increased from 13% (2005) to 26% (2006) and to 28% (2007) (P = 0.16), whereas the proportion of non-PCV7 serotypes was 48% in 2005, 31% in 2006, and 55% in 2007 (P = 0.17). The proportion of PCV7 serotypes declined also among unvaccinated carriers. The carriage of serotype 19A did not increase. Among vaccinated carriers, the rate of highly penicillin-resistant isolates decreased from year 1 to year 3, respectively, 11%, 7.7%, and 0.6% (P = 0.001), whereas the proportion of penicillin-intermediate pneumococci was 13% in 2005, 23% in 2006, and 26% in 2007 (P = 0.22). CONCLUSIONS: In Central Greece, widespread PCV vaccination was followed by a significant reduction of carriage of highly penicillin-resistant pneumococci. The frequency of penicillin-intermediate isolates did not change significantly among vaccinated carriers.