Resistance and Strategies for Streptococcus pneumoniae Vanhoof, R. - PowerPoint PPT Presentation

Resistance and Strategies for Streptococcus pneumoniae Vanhoof, R. Unit of Antibiotic Research Institute Pasteur Brussels UCL, Brussels, 07/04/2005

MICROBE RESISTANCE ACTIVITY PATHOGENICITY DEFENCE BIOTIC ANTI- S C I T E N I K TOXICITY Host

ANTIBIOTIC + � MICROBE � ANTIBIOTIC RESISTANCE PROBLEM

Streptococcus pneumoniae is one of the most important pathogens exhibiting both a high degree of morbidity and a considerable rate of mortality .

Penicillin G has been considered as the drug of choice in the treatment of pneumococcal infections, though its clinical utility has been hampered by the appearance of penicillin-insusceptible isolates.

In 1967, the first penicillin-insusceptible S. pneumoniae was reported from Australia. In Belgium, the first isolates with reduced susceptibility to penicillin were reported in 1980 by Vanhoof et al. In Belgium, steadily increase of reduced susceptibility to penicillin since 1994- 1995.

Follow-up of Antibiotic Resistance in S. pneumoniae • National Reference Centre, University Hospital Gasthuisberg. • The Belgian SPN Study Group. - Institute Pasteur Brussels. - 15 participating Centres - National Reference Centre

Factors impacting Resistance in S. Pneumoniae � Usage and clones � Geography � Population density (urban/rural) � Specimen source � Vaccine use � Travel � Social/cultural behaviour � Climate � Hospitalisation, day care, LCF � Age, gender � ……..

S. Pneumoniae: epidemiology of resistance � Resistance Rates

Evolution of Penicillin Resistance in Belgium following the Belgian SP-Study Group (Vanhoof et al) 25 21 20 16,1 15 14,7 15 12,5 12,3 %R 10 5 0 1995 1997 1999 2001 2003 2004

Evolution of Penicillin Resistance in Belgium following the National Reference Centre 17,6 18 %R 16,5 16 15,1 15 14,2 14 13 12 10 9,5 10 %R 7,6 8 7,1 6 4 4 2 2 0 1 2 3 4 5 6 7 8 9 10 11 12 1985 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003

Comparison of the Evolution of Penicillin Resistance in Belgium 25 20 Reeks1 Ref.C. 15 %R Reeks2 SP gr. 10 5 0 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004

RESULTS Resistance rates Evolution of Pen-insusceptibility 25 20 10,2 15 R % 9,3 6,4 8,4 6,2 10 I 6,6 10,8 5 8,3 6,8 6,6 6,2 5,7 0 1995 1997 1999 2001 2003 2004

Resistance rates (%): β -lactams Antibiotic 1995 1997 1999 2001 2003 2004 PEN 12.5 12.3 16.1 21.0 15.0 14.7 AMX/C 0 0 1.0 1.6 2.6 1.2 CRX 9.1 9.9 15.1 16.9 13.6 12.7 CTX 6.2 7.6 12.7 7.3 4.9 6.2

Evolution of MIC Distributions: Penicillin 70 60 1995 50 1997 40 1999 % 2001 30 2003 20 2004 10 0 2 8 3 2 5 2 8 0 0 0 1 , 0 0 0 , , 0 0 , , 0 0

Resistance rates (%): Fluoroquinolones Antibiotic 1995 1997 1999 2001 2003 2004 CIP NT NT 15.6 11.2 13.8 9.0 LEV NT NT 2.0 2.5 3.3 2.8 MOX NT NT NT NT 0.6 0.2 OFL NT NT NT NT 13.5 9.0

Resistance rates (%): MLS + TET Antibiotic 1995 1997 1999 2001 2003 2004 ERY 21.6 31.4 36.1 30.3 26.1 24.7 TEL NT NT NT NT 0.8 0.2 TET 27.3 31.1 22.9 38.5 32.3 22.1

Evolution of ERY Resistance 40 35 30 25 SPN %R 20 15 REF 10 5 0 1995 1997 1999 2001 2003 2004 Evolution of TET Resistance 40 35 30 25 SPN %R 20 15 REF 10 5 0 1995 1997 1999 2001 2003 2004

Distribution of the susceptibility Phenotypes Evolution of Phenotypes 100% 80% S 60% 4AB 3AB 40% 2AB 20% 1AB 0% 1995* 1997* 1999 2001 2003 2004

S. Pneumoniae: epidemiology of resistance � Resistance and sampling site

� MEF: 1.63 more likely than blood to be Pen-NS � MEF: 1.43 more likely than CSF to be Pen-NS Multivariate logistic regression analysis of Belgian Data (Reference Centre) by R. Mera (USA).

Impact of MEF isolates on Resistance rates (1) Penicillin Resistance Rates 40 35 30 Total 25 %R 20 Non-Inv 15 MEF 10 5 0 1995 1997 1999 2001 2003

Impact of MEF isolates on Resistance rates (2) Erythromycin Resistance Rates 60 50 40 Total %R 30 Non-Inv MEF 20 10 0 1995 1997 1999 2001 2003

RESULTS Resistance rates (%) in MEF and Non Invasive isolates Antibiotic MEF isolates Non Inv. Penicillin 26.6 15.4 0.01>P>0.001 Amoxicillin 1.1 1.0 NS Cefotaxime 1.1 3.2 NS Imipenem 3.2 3.0 NS Ciprofloxacin 9.3 14.1 NS Erythromycin 44.7 27.7 P<0.001 Tetracycline 36.2 29.8 NS

Age distribution in MEF isolates 100 80 60 % 40 20 0 0-5 6-15 16-39 40-59 60+ age

S. Pneumoniae: epidemiology of resistance � Geographic differences

Penicillin insusceptibility (%) in France (2003) Region Total Adult Pediatric France 50 43 62 48 35 68 Nord-Pas de Calais 43 38 55 Champagne-Ardennes 44 43 45 Lorraine 45 42 52 Alsace 1995 1997 1999 2001 2003 2004 France 38.0 40.5 44.0 55.0 50.0 NA P.Chahwakilian, personal communication

RESULTS Resistance rates: geographic distribution Geographic distribution of resistance 40 35 30 25 20 North % 15 South 10 Bruss 5 0 PEN CIP ERY TET Resistance CIP: Bruss < South (0.05>P>0.02)*

11.7% 44.8% 6.5% 35.7%

MIC Distributions: β -lactams 40 45 40 Amoxicillin 35 Penicillin 35 30 30 25 25 2004 2004 % 20 % 04HAIN 20 04HAIN 15 15 10 10 5 5 0 0 1 2 4 2 4 8 5 3 6 2 5 5 1 2 4 2 4 8 5 3 6 2 5 5 0 0 0 1 0 0 1 2 , 0 0 0 1 0 0 1 2 , 0 0 0 0 0 0 0 0 0 0 , , , , , , , , 0 0 0 0 0 0 0 0 , , , , , , , , 0 0 0 0 0 0 0 0 35 Cefuroxime 30 25 20 2004 % 04HAIN 15 10 5 0 0,002 0,008 0,03 0,12 0,5 2 8 32

RESULTS Resistance rates (%): β -lactams 35 32,5 30 23,4 25 22,1 20 2004 % 14,7 04HAIN 12,7 15 11,8 10 5 1,9 1,2 0 PEN**** AMX CRX*** CRXa***

RESULTS Resistance rates (%):MLS +Tetra 45 39,6 40 35 31,8 30 24,7 22,1 25 2004 % 20 04HAIN 15 10 5 0 ERY**** TET***

Distribution of the susceptibility Phenotypes Resistance Phenotypes 4 AB 3 AB 9% 2% 2 AB 15% S 49% 1 AB 25% National Resistance Phenotypes 4 AB 3 AB 1% 18% S 41% 2 AB 16% 1 AB 24% 04HAIN

S. Pneumoniae: epidemiology of resistance Resistance Mechanisms � Fluoroquinolone Resistance

FQ Resistance Mechanisms in 71 S.pneumoniae isolates (1999-2003) Type of Mechanisme % gyrA 5.6 parC 16.9 gyrA+parC 14.1 Wt and PmrA + 60.6 Wt and Pmr - 2.8

MIC distributions and type of mutation in S.pneumoniae 32 16 wt 8 parC isolates 4 gyrA 2 MIC 1 gyrA+parC 0,5 0,25

S. Pneumoniae: epidemiology of resistance Resistance Mechanisms � MLS Resistance

MLS-TET Resistance Mechanisms in S.pneumoniae isolates MLS-TET Resistance Mechanisms 100 89,7 85,2 90 80 70 56,2 60 SPgr % 50 REF 40 30 20 7,7 6 3,5 1,6 10 0 ermB mefA erm+mef tet

CONCLUSIONS

CONCLUSION (1) SUVEILLANCE OF THE RESISTANCE SUVEILLANCE OF THE RESISTANCE EPIDEMIOLOGY EPIDEMIOLOGY (resistance rates, population distributions,... (resistance rates, population distributions,... STUDY OF FACTORS WITH IMPACT ON STUDY OF FACTORS WITH IMPACT ON RESISTANCE DEVELOPMENT RESISTANCE DEVELOPMENT (clinical, geographic, demographic,…) (clinical, geographic, demographic,…) STUDY OF RESISTANCE MECHANISMS STUDY OF RESISTANCE MECHANISMS (importance of efflux, ….) (importance of efflux, ….)