An overview of the patterns of resistance in Europe. Which - PowerPoint PPT Presentation

An overview of the patterns of resistance in Europe. Which mechanisms, where, and to what extent ? J. Verhaegen, A. Vatopoulos

Macrolides Possible Phenotype Type of resistance Gene mechanism Ribosome ERY, CLI MLSB erm methiliation Ribosome ERY, CLI(nd) MLSB erm methiliation Ε R Υ M Efflux mef

Nomenclature for Macrolide and Macrolide- Lincosamide-Streptogramin B Resistance Determinants Marilyn C. Roberts, 1,* Joyce Sutcliffe, 2 Patrice Courvalin, 3 Lars Bogo Jensen, 4 Julian Rood, 5 and Helena Seppala 6 Antimicrobial Agents and Chemotherapy, December 1 999, p. 2823-2830, Vol. 43, No. 1 2

Data of Alexander Project 1 998, 1 999 and 2000. pneumococci % pen I % pen R % ery R '98 '99 '00 '98 '99 '00 '98 '99 '00 Austria 7.6 NT NT 4.8 NT NT 11 .4 NT NT Belgium 3 5.8 3.6 5 1 2.6 4.8 34 1 6.2 20.5 Czech Republic 6. 1 1 5.3 1 2 2. 1 1 1 0 Eire 7.3 NT NT 25.5 NT NT 1 2.7 NT NT France 1 2.6 1 7.2 20.7 40.7 45.3 40 47.3 58. 1 48.6 Germany 5.4 0.8 5.8 1 .8 3.9 0.8 4.2 7.8 7.4 Greece 1 6.4 1 9.4 9.6 1 5.2 29. 1 7.8 1 8. 1 25 2 1 .2 Italy 6 6.9 6.9 3 5.9 2 42 3 1 .4 28.4 Poland 5.5 5 2.6 3.5 1 5.2 6 6.2 6. 1 1 0.6 Portugal 7.0 1 2.9 20 1 0. 1 9.9 3.3 9.3 11 .7 1 6.7 Slovak Republic 20.8 1 5.5 NT 30.6 1 5.5 NT 8.3 11 .3 NT Switzerland 8.7 3.2 1 4.6 5.8 11 .2 2.9 1 8.8 8.8 8.7 The Netherlands 3.2 NT 2.3 0 NT 1 .2 2.4 NT 4.7 UK 4.6 5.9 3 1 4.9 7.8 4.5 1 8.4 8.8 1 0.4

Distribution of erythromycin-resistance phenotypes among pneumococci from 8 different European countries ( 1 998-2000) Country overall % of distribution of resistance phenotype (total N of isolates) ref erythrom ycin-resistance M LS B M other Belgium (59) 1 3 1 9 1 .5 8.5 0 Finland (65 1 ) 2 11 .2 7 1 2 1 11 .2 France (48) 3 53 1 00 0 0 Germ any ( 1 02) 4 1 0.6 74 22.5 3.5 Greece ( 1 40) 5 1 8 67.9 29.2 3.6 Italy (85) 6 3 1 .7 76.5 23.5 0 Norway (8) 7 4.5 75 25 0 Spain ( 1 09) 8 36. 1 84 1 5 1

Resistance to macrolides in Streptococci C o u n t r y R e f e r e n c e % R t o E r y P h e n o t y p e s F in l a n d 1 1 M : 8 0 % S p a i n 1 2 1 7 . 6 % E r y R : 1 7 . 6 % C l i R : 0 . 5 % S p a i n 1 3 3 6 . 7 % S p a i n 1 4 2 3 . 5 % M : 9 5 . 6 % S p a i n 1 5 2 9 . 2 % M : 9 0 % B e l g i u m 1 6 6 . 5 % M : 8 4 % C R : 1 6 % F r a n c e 1 7 1 0 % M : < 0 . 1 % F r a n c e 1 8 6 . 2 % C R : 3 . 4 % M : 2 . 8 % I t a l y 1 9 4 1 . 2 - 4 3 . 5 % M : 2 1 . 2 - 4 0 % I R : 4 0 . 9 - 1 7 . 5 % C R : 3 7 . 9 - 4 2 . 5 % I t a l y 2 0 M : 4 2 , 4 % I R : 1 1 , 9 % C R : 2 1 , 6 % I t a l y 2 1 3 8 . 5 % C R in 1 9 9 6 M in 1 9 9 8 I t a l y 2 2 3 1 . 0 9 % S p a i n 2 2 2 6 . 6 % T u r k e y 2 2 4 . 8 % F r a n c e 2 2 3 . 8 % S w e d e n 2 2 3 . 7 % G r e e c e 2 3 2 3 . 9 % E r y R : 2 3 . 9 % C l i n R : 2 . 1 % G r e e c e 2 4 1 5 . 2 % M : 5 1 . 9 % G r e e c e 2 5 3 0 . 8 % M : 5 9 . 5 % I R : 4 0 . 5 % G e r m a n y 2 6 1 2 . 7 % M : 1 0 % I R : 5 5 % C R : 3 5 % P o r t u g a l 2 7 3 5 . 8 % M : 1 6 . 7 % C R : 7 9 . 6 %

Table 1: Susceptibilities of clinical isolates of Streptococccus pneum oniae and Streptococcus. pyogenes to the antim icrobials used in this study. Antibiotic BREAK PO INTS ( μ g/ml) % R % I M IC50 M IC90 G . M ean Range Streptococcus pneumoniae (n= 145) S ≤ 0.064 R ≥ 2 Penicillin G 9.7 40.7 0.094 1 0.091 0.003 - 16 Cefotaxime S ≤ 0.5 R ≥ 2 5.5 15.9 0.125 1 0.106 0.004 - 4 S ≤ 0.25 R ≥ 1 Erythromycin 42.8 3.4 0.25 256 1.253 0.023 - 256 S ≤ 0.25 R ≥ 1 49 3.4 1 32 0.896 0.0064 - Clarithromycin 256 Clindamycin S ≤ 0.25 R ≥ 1 13.8 16.6 0.19 3 0.353 0.019 - 256 Levofloxacin S ≤ 2 R ≥ 8 0 1.4 0.75 1 0.654 0.19 - 4 Doxycycline S ≤ 2 R ≥ 8 11.7 10.3 0.19 6 0.323 0.023 - 24 Chloramphenicol S ≤ 4 R ≥ 8 14.5 0 1.5 12 1.936 0.064 - 256 Cotrimoxazole S ≤ 0.5/9.5 R ≥ 4/76 29.9 26.4 0.75 32 1.161 0.023 - 32 Telithromycin S ≤ 0.5 R ≥ 2 3,4 8.3 0.094 0 .75 0, 11 4 0.008 – 6 Streptococcus pyogenes (n= 161) S ≤ 0. 1 25 R ≥ 4 Penicillin G 0 0 0.008 0.0 1 2 0.009 0.0008 - 0. 1 6 S ≤ 0.5 R ≥ 2 Cefotaxime 0 0 0.023 0.047 0.02 1 0.006 - 0.47 S ≤ 0.25 R ≥ 1 Erythromycin 30.8 3. 1 0. 1 9 32 0.622 0.0 1 6 – 256 S ≤ 0.25 R ≥ 1 Clarithromycin 28.8 3. 1 0.094 24 0.337 0.0047 – 256 S ≤ 0.25 R ≥ 1 Clindamycin 1 .2 3.8 0. 1 25 0.25 0. 1 36 0.0094 - 0.75 S ≤ 2 R ≥ 8 Levofloxacin 0 3. 1 0 .5 1 0.498 0.038 – 5 S ≤ 2 R ≥ 8 Doxycycline 20.6 0.6 0. 1 25 8 0.25 1 0.0 1 25 – 32 S ≤ 4 R ≥ 8 Chloramphenicol 0 0 2 3 1 .67 1 0.047 – 4 S ≤ 0.5/9.5 R ≥ 4/76 Cotrimoxazole 1 6.2 1 0 0 .25 32 0.4 1 4 0.0 1 2 – 32 S ≤ 0.5 R ≥ 2 Telithromycin 3. 1 11 .2 0.064 1 0.08 1 0.008 – 2

Table 2: Resistance phenotypes to erythromycin and clindamycin of the erythromycin resistant (MIC > 0.5 μ g/ml) isolates. Streptococcus pneumoniae Streptococcus pyogenes Phenotype* No. % No. % CR 1 6 40.0 0 0 IR 1 2.5 1 7 40.5 M 23 57.5 25 59.5 All tested 40 100.0 42 100.0 CR: constitutive type of MLS B resistance IR: inducible type of MLS B resistance M: M phenotype (efflux mechanism)

Resistance to macrolides in Greece S. pneumoniae 35 S. pyogenes 30 25 20 15 10 5 0 95-96 96-97 97-98 98-99 99-00

Conclusions • Resistance to macrolides has increased all across Europe – Differences in rates of isolation do exist. • This increase is due to the spread of different genes (the erm group and the mef group of genes) • Each country presents different epidemiology and must be regarded separately.