pneumococcus: antibiotic resistance in the region · resistant to both penicillin and erythromycin...
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Pneumococcus:Antibiotic Resistance
in the Region
Çiğdem Bal KayacanIstanbul University
Istanbul Faculty of MedicineDepartment of Microbiology & Clinical Microbiology
Drug Resistance in S.pneumoniae
penicillin macrolide
trim/sulfa quinolone
tetracycline
PenicillinNon-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 ratehigh in many countries
• Pneumococcal strainsresistant to both penicillinand erythromycinincreasing faster thanstrains singly resistant toeither
• Significant increase in MDR-S.pneumoniae since 1990s
McCormick AW et al. Nat Med 2003; 9:424File Jr. Clin Microbiol Infect 2006; 12(Suppl
3):31
M-type (Efflux)low level resistance tomacrolides (14-, 15-)
MIC = 1-32 μg/mL
MLSB-typehigh level resistance tomacrolides,
lincosamides, streptogramin B
MIC ≥ 64 μg/mL
PenicillinNon-SusceptibleS.pneumoniae
the ALEXANDER PROJECT
WORLDWIDE
13,9
14,7
16
12,7
17,1
15,9
0
10
20
30
40
EUROPE LATINAMERICA
NORTHAMERICA
PRSP
PISP
28,6 28,733
PNSP
SENTRY1999-2003
EUROPE
3,9
25,8
29,7
0
5
10
15
20
25
30
PRSPPISPPNSP
1996-97national
multicenter
respiratory isolates
TURKEY
PNSP
TURKEY: PNSP in National Studies
PISP PRSPStudy Period
29,7 29
39,5
34,232,2
39
17,8
0
5
10
15
20
25
30
35
40
1996-1997
Gür
1999-2002
Altun
1999-2003
PROTEKT
2002-2003
e-BASKETT
2004-2005
SOAR
2001-2004
Yalçın ARMed
PNSPPISPPRSP
Multicenter Studies;Last 10 Years
respiratory invasive
TURKEY
PNSP
36,940,9
5
27,6
5
20,5
51,9
62,6
8
25,7
0
10
20
30
40
50
60
70
PNSP Erythro DUAL Trim/Sulfa Tetra
19972005
OVERALL• PRSP 2.4% PISP 30%• Significant increase in the mean MIC’s of PENICILLIN
Gür D, Güçiz Doğan B. (P754) ECCMID 2006
9 year period1406 isolates
Pediatric Isolates
PNSP:Overall
in Turkey
27,3
2,3
27,8
3,4
32,7
7,4
0
5
10
15
20
25
30
35
40
45
1990-1995 1995-2000 2000-2004
PRSPPISP
40,1
31,229,6
TURKEY
TURKEY
0
10
20
30
40
50
60
70
GREECE ISRAEL RUSSIA S.ARABIA TURKEY
PNSPPISPPRSP
PROTEKT 2002-2003REGION
PNSP
respiratory
isolates
European Antimicrobial ResistanceSurveillance System (EARSS)
Highest levels of antibiotic resistance
within theMediterranean
countries
www.earss.rivm.nl
2006Austria ItalyBelgium LatviaBulgaria LithuaniaCroatia LuxembourgCyprus Malta Czech Republic NetherlandsDenmark NorwayEstonia PolandFinland PortugalFrance RomaniaGermany SloveniaGreece SpainHungary SwedenIceland Turkey*Ireland United KingdomIsrael
7
29
6
7
31
13
5
0
10
20
30
40
BULG
ARIA
ISRA
EL
CYPR
US
TURK
EY
PRSP
PISP
EARSS 2006
7
3538
18 REGION
PNSP
invasive isolates
EARSS: PNSP 2006
invasive
isolates
RO
BU
ISR
CYP
CHANGE in CLSI BREAKPOINTSfor Spn & Penicillin
• PRSP: MICPenicillin ≥ 2 μg/mL• PNSP: MICPenicillin > 0.06 μg/mL
• 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/mLPRSP ≥ 8 μg/mL
2007
2008
ErythromycinErythromycinResistanceResistance
in S.in S.pneumoniaepneumoniae
the ALEXANDER PROJECT
penicillin resistance
erythromycin resistance
PROTEKT
2001-2004
PROTEKT-global
Erythromycin MICsare increasing !
Effluxfor
macrolideresistance
PROTEKT
Antibiotic Resistance Surveillance andControl in the Mediterranean Region:
The ARMed Project
Algeria, Cyprus, Egypt, Jordan, Lebanon, Malta, Morocco, Tunisia and TurkeyMA 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 southeasternMediterranean – preliminary results from the ARMed project. Euro Surveill 2006;11(7):164
invasive isolates
ARMED
2003-2004
Erythromycin Resistance
16 17
31
16
0
10
20
30
BULGARIA ISRAEL CYPRUS TURKEY
EARSS 2006
15
30
7
11
0
5
10
15
20
25
30
35
40
45
PENICILLIN ERYTHROMYCIN
PRSP
PISPEFFLUX
MLSB
GREECE 2002-2003
GRASP STUDY20 countries
mixt isolates
45
18
erythromycinresistance
EARSS 2006
32,2
16,98,5 5,3 1,3
0
10
20
30
PNSP ERY TET CMLAM/CLAV
PRSP 7.6%PISP 24.6%
TURKEY
respiratory isolates
SOAR in AME2004-2005
Penicillin+Erythromycin
DUAL Resistance
in S.pneumoniae
the ALEXANDER PROJECT
of PRSP
erythromycinresistant
13
EARSS 2004
Penicillin+ErythromycinDual Resistance
in S.pneumoniae
DUAL resistance
EARSS 2006
SEROTYPES SEROTYPES & &
RESISTANCERESISTANCE
TURKEY
EARSS 2006
serogroups & resistance
EARSS 2005 - 2006 Report
Serogroup information from 11 countriesHighest resistance in serogroups 6,9,14,19,23,1,33Penicillin resistance in serogroups 14,9,19,6 and 23
Erythromycin resistance in serogroups 1 and 33
7-valent conjugate vaccine covers all serogroups withpenicillin resistance
In contrast to the 23-valent vaccine, it does not cover serogroup 1 and 33 in which erythromycinresistance is common
It can be expected that the introduction of thisvaccine into the official childhood vaccination programsin many European countries will have considerableimpact on control of penicillin resistance in S.pneumoniae
34,7
20,3
14,4
33,5
21,9
3,5
48,3
22,5
25,8
48,3
35,9
23,2
0
10
20
30
40
50
Pediatric Carriage Adult Infection
PNSPPISPPRSPERYDUALCIP
7-valentpneumococcal
conjugate vaccineestimatedto provide
coverage against71.7% of paediatriccarriage isolates & 51.3% of adultclinical isolates
Serotypes19F, 14, 23F
and 6B most prevalent
among carriage andclinical isolates
9V
9V
GREECE
2004-2006
isolates expressing the erm(B)+mef(A) macrolide-resistant genotype increased
NVS 19A VS 19Fyear 1 7.8% 86.7%year 4 45.5% 51.7%
Antimicrobial Resistance amongVaccine Serotypes No Increase
in 3 years
0
10
20
30
40
50
60
70
PRSP
PISP
ERYTH
RO
AMOX/CLAV
COTRIM MDR
2000–2001 2003–2004
bloodnon-blood
Farrell DJ, Klugman KP, Pichichero M. Pediatr Infect Dis J 2007;26:123
0
10
20
30
40
50
60
70
PRSP PIS
P
ERYT
HRO
AMOX
/CLA
V
COTR
IMMDR
2000–2001
2003–2004
Antimicrobial Resistance amongNon-Vaccine Serotypes Increase
in 3 years
PRSP
PISP
ERYTH
RO
AMOX/CLAV
COTRIM MDR
0
5
10
15
20
25
30
35 2000–2001 2003–2004
non-blood
0
5
10
15
20
25
PRSP
PISP
ERYT
HRO
AMOX/
CLAV
COTR
IM MDR
2000–2001 2003–2004
blood
Farrell DJ, Klugman KP, Pichichero M. Pediatr Infect Dis J 2007;26:123
Summary: TURKEY
PNSP= 40%PRSP= 5-10%
Erythromycin= 15-20%Trim/Sulfa > 50%Tetra <10%Amox/Clav <5%Nearly all isolates susceptible torifampicin, quinolones, linezolid, quinupristin-dalfopristin & telithromycin
Summary: REGIONCyprus, 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 ratessimilar to Turkey’s (16-17%) in invasive & respiratoryisolatesCyprus, Lebanon- macrolide resistance high (> 30%)
Region- Dual Resistance 10-25%, 5-10% in Turkey