Pneumococcus: Antibiotic Resistance in the Region
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1 Pneumococcus: Antibiotic Resistance in the Region Çiğdem Bal Kayacan Istanbul University Istanbul Faculty of Medicine Department of Microbiology & Clinical Microbiology
2 Drug Resistance in S.pneumoniae penicillin macrolide trim/sulfa quinolone tetracycline
3 Penicillin Non-Susceptible S.pneumoniae (PNSP) Penicillin Intermediate (PISP) MIC = μg/ml Penicillin Resistant (PRSP) MIC 2 μg/ml By changes in PBPs 2B, 2X and 1A Rates HIGHER in pediatric patients & respiratory infections
4 MACROLIDE Resistance in S.pneumoniae Macrolide resistance rate high in many countries Pneumococcal strains resistant to both penicillin and erythromycin increasing faster than strains singly resistant to either Significant increase in MDR-S.pneumoniae since 1990s McCormick AW et al. Nat Med 2003; 9:424 File Jr. Clin Microbiol Infect 2006; 12(Suppl 3):31 M-type (Efflux) low level resistance to macrolides (14-, 15-) MIC = 1-32 μg/ml MLS B -type high level resistance to macrolides, lincosamides, streptogramin B MIC 64 μg/ml
5 Penicillin Non-Susceptible S.pneumoniae
6 the ALEXANDER PROJECT WORLDWIDE
7 PNSP 40 28,6 28,7 33 SENTRY ,7 12,7 15,9 PRSP PISP 10 13, ,1 0 EUROPE EUROPE LATIN NORTH AMERICA AMERICA
8 national multicenter ,8 29,7 TURKEY respiratory isolates PNSP 10 PRSP PISP PNSP 5 0 3,9
9 TURKEY: PNSP in National Studies Study Period PISP PRSP
10 ,7 Multicenter Studies; Last 10 Years 29 39,5 34,2 32,2 PNSP PISP PRSP TURKEY 39 PNSP , respiratory Gür Altun PROTEKT e-baskett SOAR Yalçın invasive ARMed
11 70 Gür D, Güçiz Doğan B. (P754) ECCMID ,9 36, ,9 62,6 9 year period 1406 isolates Pediatric Isolates 30 27,6 25, , PNSP Erythro DUAL Trim/Sulfa Tetra OVERALL PRSP 2.4% PISP 30% Significant increase in the mean MIC s of PENICILLIN
12 PNSP: Overall in Turkey ,6 2,3 PRSP PISP 3,4 31,2 40,1 7, ,3 27,8 32,
13 TURKEY TURKEY
14 PNSP REGION PNSP PISP PRSP PROTEKT respiratory isolates GREECE ISRAEL RUSSIA S.ARABIA TURKEY
15 European Antimicrobial Resistance Surveillance System (EARSS) Austria Belgium Bulgaria Croatia Cyprus Czech Republic Denmark Estonia Finland France Germany Greece Hungary Iceland Ireland Israel 2006 Italy Latvia Lithuania Luxembourg Malta Netherlands Norway Poland Portugal Romania Slovenia Spain Sweden Turkey* United Kingdom Highest levels of antibiotic resistance within the Mediterranean countries
16 PRSP PISP 31 PNSP REGION BULGARIA 7 7 ISRAEL CYPRUS 7 TURKEY 13 EARSS 2006 invasive isolates
17 EARSS: PNSP 2006 invasive isolates RO BU CYP ISR
18 CHANGE in CLSI BREAKPOINTS for Spn & Penicillin 2007 PRSP: MIC Penicillin 2 μg/ml PNSP: MIC Penicillin > 0.06 μg/ml 2008 Same for oral Pen V Lowered for parenteral for meningitis: PNSP=PRSP 0.12 μg/ml (No Low Level) Highered for parenteral for non-meningitis: PNSP 4 μg/ml PRSP 8 μg/ml
19 Erythromycin Resistance in S.pneumoniae
20 the ALEXANDER PROJECT
21 P R O T E K T penicillin resistance erythromycin resistance
22 PROTEKT-global Erythromycin MICs are increasing!
23 Efflux for macrolide resistance PROTEKT
24 Antibiotic Resistance Surveillance and Control in the Mediterranean Region: The ARMed Project Algeria, Cyprus, Egypt, Jordan, Lebanon, Malta, Morocco, Tunisia and Turkey MA Borg, E Scicluna, M de Kraker, N van de Sande-Bruinsma, E Tiemersma, D Gür, S Ben Redjeb, O Rasslan, Z Elnassar, M Benbachir, D Pieridou Bagatzouni, K Rahal, Z Daoud, H Grundmann, J Monen. Antibiotic resistance in the southeastern Mediterranean preliminary results from the ARMed project. Euro Surveill 2006;11(7):164
25 invasive isolates ARMED
26 Erythromycin Resistance EARSS BULGARIA ISRAEL CYPRUS TURKEY
27 GRASP STUDY 20 countries GREECE PRSP 18 mixt isolates PISP 11 EFFLUX 7 0 MLS B PENICILLIN ERYTHROMYCIN
28 EARSS 2006 erythromycin resistance
29 SOAR in AME PRSP 7.6% PISP 24.6% TURKEY respiratory isolates ,2 16,9 8,5 5,3 1,3 PNSP ERY TET CML AM/CLAV
30 Penicillin+Erythromycin DUAL Resistance in S.pneumoniae
31 the ALEXANDER PROJECT 1 3 of PRSP erythromycin resistant
32 EARSS 2004 Penicillin+Erythromycin Dual Resistance in S.pneumoniae
33 EARSS 2006 DUAL resistance
34 SEROTYPES & RESISTANCE
35 TURKEY
36 EARSS 2006 serogroups & resistance
37 EARSS Report Serogroup information from 11 countries Highest resistance in serogroups 6,9,14,19,23,1,33 Penicillin resistance in serogroups 14,9,19,6 and 23 Erythromycin resistance in serogroups 1 and 33 7-valent conjugate vaccine covers all serogroups with penicillin resistance In contrast to the 23-valent vaccine, it does not cover serogroup 1 and 33 in which erythromycin resistance is common It can be expected that the introduction of this vaccine into the official childhood vaccination programs in many European countries will have considerable impact on control of penicillin resistance in S.pneumoniae
38 GREECE 34,7 33,5 21,9 20,3 14,4 3,5 Pediatric Carriage 9V 48,3 48,3 35,9 25,8 22,5 Adult Infection 23,2 9V PNSP PISP PRSP ERY DUAL CIP 7-valent pneumococcal conjugate vaccine estimated to provide coverage against 71.7% of paediatric carriage isolates & 51.3% of adult clinical isolates Serotypes 19F, 14, 23F and 6B most prevalent among carriage and clinical isolates
39 isolates expressing the erm(b)+mef(a) macrolide-resistant genotype increased NVS 19A VS 19F year 1 7.8% 86.7% year % 51.7%
40 Antimicrobial Resistance among Vaccine Serotypes No Increase in 3 years 70 blood non-blood PRSP PISP ERYTHRO AMOX/CLAV COTRIM MDR 0 PRSP PISP ERYTHRO AMOX/CLAV COTRIM Farrell DJ, Klugman KP, Pichichero M. Pediatr Infect Dis J 2007;26:123 MDR
41 Antimicrobial Resistance among Non-Vaccine Serotypes Increase in 3 years blood non-blood PRSP PISP ERYTHRO AMOX/CLAV COTRIM MDR 0 PRSP PISP ERYTHRO AMOX/CLAV COTRIM Farrell DJ, Klugman KP, Pichichero M. Pediatr Infect Dis J 2007;26:123 MDR
42 Summary: TURKEY PNSP= 40% PRSP= 5-10% Erythromycin= 15-20% Trim/Sulfa > 50% Tetra <10% Amox/Clav <5% Nearly all isolates susceptible to rifampicin, quinolones, linezolid, quinupristin-dalfopristin & telithromycin
43 Summary: REGION Cyprus, Israel, Romania- High rates of PNSP (>35%) Lebanon- Highest rate of PNSP (>65%) Egypt, Jordan, Morocco, Malta, Tunisia, Algeria- PNSP rates lowest (5-15%) in invasive isolates Greece, Bulgaria, Israel- macrolide resistance rates similar to Turkey s (16-17%) in invasive & respiratory isolates Cyprus, Lebanon- macrolide resistance high (> 30%) Region- Dual Resistance 10-25%, 5-10% in Turkey
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