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

Phenotype Type of resistance Possible mechanism Gene ERY, CLI MLSB Ribosome methiliation erm ERY, CLI(nd) MLSB Ribosome methiliation erm ΕRΥ 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 Seppala6

Antimicrobial Agents and Chemotherapy, December 1999, p. 2823-2830, Vol. 43, No. 12

Data of Alexander Project 1998, 1999 and 2000. pneumococci

% pen I % pen R % ery R '98 '99 '00 '98 '99 '00 '98 '99 '00 Austria Belgium Czech Republic Eire France Germany Greece Italy Poland Portugal Slovak Republic Switzerland The Netherlands UK 7.6 3 6.1 7.3 12.6 5.4 16.4 6 5.5 7.0 20.8 8.7 3.2 4.6 NT 5.8 1 NT 17.2 0.8 19.4 6.9 5 12.9 15.5 3.2 NT 5.9 NT 3.6 5.3 NT 20.7 5.8 9.6 6.9 2.6 20 NT 14.6 2.3 3 4.8 5 1 25.5 40.7 1.8 15.2 3 3.5 10.1 30.6 5.8 14.9 NT 12.6 2 NT 45.3 3.9 29.1 5.9 15.2 9.9 15.5 11.2 NT 7.8 NT 4.8 2.1 NT 40 0.8 7.8 2 6 3.3 NT 2.9 1.2 4.5 11.4 34 1 12.7 47.3 4.2 18.1 42 6.2 9.3 8.3 18.8 2.4 18.4 NT 16.2 1 NT 58.1 7.8 25 31.4 6.1 11.7 11.3 8.8 NT 8.8 NT 20.5 NT 48.6 7.4 21.2 28.4 10.6 16.7 NT 8.7 4.7 10.4

Distribution of erythromycin-resistance phenotypes among pneumococci from 8 different European countries (1998-2000)

distribution of resistance phenotype Country (total N of isolates) ref

• verall % of

erythrom ycin-resistance M LS

B

M

• ther

Belgium (59) Finland (651) France (48) Germ any (102) Greece (140) Italy (85) Norway (8) Spain (109) 1 2 3 4 5 6 7 8 31 11.2 53 10.6 18 31.7 4.5 36.1 91.5 71 100 74 67.9 76.5 75 84 8.5 21 22.5 29.2 23.5 25 15 11.2 3.5 3.6 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 (μg/ml) % R % I M IC50 M IC90 G . M ean Range Streptococcus pneumoniae (n= 145) Penicillin G S ≤ 0.064 R ≥ 2 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 Erythromycin S ≤ 0.25 R ≥1 42.8 3.4 0.25 256 1.253 0.023 - 256 Clarithromycin S ≤ 0.25 R ≥ 1 49 3.4 1 32 0.896 0.0064 - 256 Clindamycin S ≤ 0.25 R ≥ 1 13.8 16.6 0.19 3 0.353 0.019 - 256 Levofloxacin S ≤ 2 R ≥ 8 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 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 0,114 0.008 – 6 Streptococcus pyogenes (n= 161) Penicillin G S ≤ 0.125 R ≥ 4 0.008 0.012 0.009 0.0008 - 0.16 Cefotaxime S ≤ 0.5 R ≥ 2 0.023 0.047 0.021 0.006 - 0.47 Erythromycin S ≤ 0.25 R ≥ 1 30.8 3.1 0.19 32 0.622 0.016 – 256 Clarithromycin S ≤ 0.25 R ≥ 1 28.8 3.1 0.094 24 0.337 0.0047 – 256 Clindamycin S ≤ 0.25 R ≥ 1 1.2 3.8 0.125 0.25 0.136 0.0094 - 0.75 Levofloxacin S ≤ 2 R ≥ 8 3.1 0 .5 1 0.498 0.038 – 5 Doxycycline S ≤ 2 R ≥ 8 20.6 0.6 0.125 8 0.251 0.0125 – 32 Chloramphenicol S ≤ 4 R ≥ 8 2 3 1.671 0.047 – 4 Cotrimoxazole S ≤ 0.5/9.5 R ≥ 4/76 16.2 10 0 .25 32 0.414 0.012 – 32 Telithromycin S ≤ 0.5 R ≥ 2 3.1 11.2 0.064 1 0.081 0.008 – 2

Table 2: Resistance phenotypes to erythromycin and clindamycin of the erythromycin resistant (MIC > 0.5 μg/ml) isolates. Streptococcus pneumoniae Streptococcus pyogenes Phenotype* No. % No. % CR 16 40.0 IR 1 2.5 17 40.5 M 23 57.5 25 59.5 All tested 40 100.0 42 100.0 CR: constitutive type of MLSB resistance IR: inducible type of MLSB resistance M: M phenotype (efflux mechanism)

Resistance to macrolides in Greece

5 10 15 20 25 30 35 95-96 96-97 97-98 98-99 99-00

• S. pneumoniae
• S. pyogenes

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.