Pneumococcus: Antibiotic Resistance in the Region Çiğdem Bal Kayacan Istanbul University Istanbul Faculty of Medicine Department of Microbiology & Clinical Microbiology
Drug Resistance in S.pneumoniae penicillin macrolide trim/sulfa quinolone tetracycline
Penicillin Non-Susceptible S.pneumoniae (PNSP) Penicillin Intermediate (PISP) MIC = 0.12-1 μg/ml Penicillin Resistant (PRSP) MIC 2 μg/ml By changes in PBPs 2B, 2X and 1A Rates HIGHER in pediatric patients & respiratory infections
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
Penicillin Non-Susceptible S.pneumoniae
the ALEXANDER PROJECT WORLDWIDE
PNSP 40 28,6 28,7 33 SENTRY 1999-2003 30 20 14,7 12,7 15,9 PRSP PISP 10 13,9 16 17,1 0 EUROPE EUROPE LATIN NORTH AMERICA AMERICA
1996-97 national multicenter 30 25 25,8 29,7 TURKEY respiratory isolates 20 15 PNSP 10 PRSP PISP PNSP 5 0 3,9
TURKEY: PNSP in National Studies Study Period PISP PRSP
40 35 30 25 29,7 Multicenter Studies; Last 10 Years 29 39,5 34,2 32,2 PNSP PISP PRSP TURKEY 39 PNSP 20 15 17,8 10 5 0 respiratory 1996-1997 Gür 1999-2002 Altun 1999-2003 PROTEKT 2002-2003 e-baskett 2004-2005 SOAR 2001-2004 Yalçın invasive ARMed
70 Gür D, Güçiz Doğan B. (P754) ECCMID 2006 60 50 40 40,9 36,9 1997 2005 51,9 62,6 9 year period 1406 isolates Pediatric Isolates 30 27,6 25,7 20 20,5 10 5 5 8 0 PNSP Erythro DUAL Trim/Sulfa Tetra OVERALL PRSP 2.4% PISP 30% Significant increase in the mean MIC s of PENICILLIN
PNSP: Overall in Turkey 45 40 35 30 25 29,6 2,3 PRSP PISP 3,4 31,2 40,1 7,4 20 15 10 27,3 27,8 32,7 5 0 1990-1995 1995-2000 2000-2004
TURKEY TURKEY
PNSP 70 60 50 40 30 REGION PNSP PISP PRSP PROTEKT 2002-2003 respiratory isolates 20 10 0 GREECE ISRAEL RUSSIA S.ARABIA TURKEY
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 www.earss.rivm.nl
40 35 38 30 6 PRSP PISP 31 PNSP 20 18 REGION 29 5 10 0 BULGARIA 7 7 ISRAEL CYPRUS 7 TURKEY 13 EARSS 2006 invasive isolates
EARSS: PNSP 2006 invasive isolates RO BU CYP ISR
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
Erythromycin Resistance in S.pneumoniae
the ALEXANDER PROJECT
P R O T E K T penicillin resistance 2001-2004 erythromycin resistance
PROTEKT-global Erythromycin MICs are increasing!
Efflux for macrolide resistance PROTEKT
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
invasive isolates ARMED 2003-2004
Erythromycin Resistance EARSS 2006 30 31 20 16 17 16 10 0 BULGARIA ISRAEL CYPRUS TURKEY
GRASP STUDY 20 countries 45 45 40 35 30 30 GREECE 2002-2003 25 20 PRSP 18 mixt isolates 15 10 5 15 PISP 11 EFFLUX 7 0 MLS B PENICILLIN ERYTHROMYCIN
EARSS 2006 erythromycin resistance
SOAR in AME 2004-2005 30 PRSP 7.6% PISP 24.6% TURKEY respiratory isolates 20 10 0 32,2 16,9 8,5 5,3 1,3 PNSP ERY TET CML AM/CLAV
Penicillin+Erythromycin DUAL Resistance in S.pneumoniae
the ALEXANDER PROJECT 1 3 of PRSP erythromycin resistant
EARSS 2004 Penicillin+Erythromycin Dual Resistance in S.pneumoniae
EARSS 2006 DUAL resistance
SEROTYPES & RESISTANCE
TURKEY
EARSS 2006 serogroups & resistance
EARSS 2005-2006 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
2004-2006 50 40 30 20 10 0 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
isolates expressing the erm(b)+mef(a) macrolide-resistant genotype increased NVS 19A VS 19F year 1 7.8% 86.7% year 4 45.5% 51.7%
Antimicrobial Resistance among Vaccine Serotypes No Increase in 3 years 70 blood 2000 2001 70 2000 2001 2003 2004 non-blood 60 2003 2004 60 50 50 40 40 30 30 20 20 10 10 0 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
Antimicrobial Resistance among Non-Vaccine Serotypes Increase in 3 years blood 35 30 non-blood 2000 2001 2003 2004 25 2000 2001 2003 2004 25 20 20 15 15 10 10 5 5 0 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
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
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