Dyn ynamics of Non-susceptib ible le S. . pneumoniae nasopharyngeal colo lonization in in hospit italized child ildren <5 5 years old ld, , in in Southern Is Israel, , early ly and post PCV's 's im imple lementation Dana Danino, Noga Givon-Lavi, Shalom Ben-Shimol, David Greenberg, Ron Dagan The Pediatric Infectious Disease Unit Soroka University Medical Center Ben-Gurion University Beer-Sheva, Israel
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Pneumococcal nasopharyngeal colonization Site of potential Port of entry for Source of acquisition of mucosal and transmission antibiotic invasive infections resistance Children < 5 years are the main carriers, and thus also the main transmitters
PCVs impact on pneumococcal carriage VT13 Non VT13 Within-serotype (Replacement) nonsusceptibility (Continuous antibiotic pressure) +/- ? Overall carriage
Methods • An ongoing, prospective, population-based, active surveillance, one hospital serving the entire population • Vaccination program and Vaccine uptake ≥ 2 doses PCV7- PCV7 - PCV13- private NIP + NIP market catch-up NIP= national immunization program • Every working day, 8 children <5 years, visiting the pediatric emergency room were enrolled, since Nov 2009 • Methodology of nasopharyngeal cultures, microbiology, serotyping and susceptibility testing were previously described ( Dagan et al, JID, 211:1144, 2015, Human Vaccine Immunother , 12(2): 268-276,2016 )
Antibiotic non-susceptibility rates between VT13 and non-VT13 carried serotypes prior to the impact of PCVs (07/2009-06/2010) VT13 serotypes (n=318) Non VT13 serotypes (n=261) % <0.001 % <0.001 % % of all positive cultures % <0.001 % <0.001 <0.001 % <0.001 % % % S= susceptible, Pen= penicillin, Ery= erythromycin, Clind= clindamycin
Dynamics of pneumococcal carriage, 2009 - 2015 PCV13 PCV 13 PCV7 PCV PCV PCV7 NIP private NIP + market catch-up Over erall all Pneumococcal car neumococcal carria riage ge % (n= (n=4,166) % <0.001* Non VT Non VT13 13 ser eroty otypes pes % % of all cultures (n= (n=2,962) ) <0.001* % % VT13 serotypes (n=1,204) % <0.001* %
Antibiotic non-susceptibility rates: all non-VT13 serotypes (N=2,962) 2009-10 2014-15 50 % 1.2 (1.0-1.4)* 40 % % of non-VT13 positive cultures 1.9 (1.4-2.5)* 30 % % 20 2.7 (1.6-4.3)* 1.6 (1.0-2.5)* 2.6 (1.5-4.3)* 2.6 (1.4-5.1)* % 10 % 0 S= susceptible, Pen= penicillin, Ery= erythromycin, Clind= clindamycin * Rate ratio (confidence intervals)
Dynamics in Non-susceptibility; 5 most common non-VT13 serotypes 2014-15 2009-10 15A 15B/C (n=178) (n=367) % % % of Non-VT13 positive cultures * % % % % * * * % % % % % % % % % 23B 16F 11A (n=202) (n=220) (n=160) * % % % % of Non-VT13 positive cultures * % % % * % % % % % % % % % % % % % % Pen= penicillin, Ery= erythromycin, Clind= clindamycin * =P value <0.05 ; trend in proportion for all years 2009-10 – 2014-15
Impact of PCV on overall non-susceptible pneumococcal carriage (N=8,537) 2009-10 2014-15 35 % 0.6 (0.6-0.7)* 30 % 25 % 0.7 (0.6-0.8)* % of all cultures 20 % 0.6 (0.5-0.7)* % 0.6 (0.5-0.7)* 15 0.7 (0.6-0.8)* 0.5 (0.4-0.7)* % 10 % 5 % 0 Pnc= pneumococcal, S= susceptible, Pen= penicillin, Ery= erythromycin, Clind= clindamycin * Rate ratio (confidence intervals)
Conclusions o PCVs impact on non-susceptible pneumococcal carriage, is derived from 4 different components: VT13 v Overall carriage v Non-VT13 Intra-serotype non-susceptibility o PCV7/PCV13 introduction to the Israeli national immunization program reduced non-susceptible pneumococcal carriage from first to sixth year o Non-responsible overuse of antibiotics is still prevalent and an ongoing risk for rebound of antibiotic resistance among pneumococci
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