TWENTY YEARS OF ANTIBIOTIC RESISTANCE IN NON- INVASIVE STREPTOCOCCUS PNEUMONIAE ISOLATED IN BELGIUN (1995 214). Vanhoof, R. MD, PhD Dep. Transmissible & Infectious Diseases Unit of Antibiotic Research 21/5/215 Brussels, IPH Seminar Rue Engelandstraat 642 118 Brussels Belgium T +32 2 373.32.61 F +32 2 373.32.68 email: raymond.vanhoof@wiv-isp.be www.wiv-isp.be
Collection of isolates from 1995 to 214 (n = 5.442) 15 Participating centres: Antwerpen, AZ Stuyvenberg - K. Camps & Vande Vyvere, M. Arlon, Cl. St.Joseph - P. & J-B Goffinet. Bonheiden, ImeldaZH - J. Frans & R. VanNoyen Brugge Boussu, CHR Warquignies I. Philippart Brugge, AZ St.Jan E. Nulens, B.Gordts & Roeselare H. Van Landuyt Brussels, Cebiodi B. Mulongo & O.Fagnart Gent, AZ J.Palfijn L.Ide & L. VanNimmen Haine-St-Paul, Hôp Jolimont Mukuku Sifa & F. Meunier Hasselt, VirgaJesse ZH R. Cartuyvels & K. Magerman Liège, Hôp Citadelle M. Carpentier Leuven, MCH M. Lontie & B. Van Meensel Marche-en-Famenne, Hôp Princesse Paola P. Lefèvre Montigny-le-Tilleul, CHR A.Vésale D. Govaerts Roeselare, H.Haert ZH E. De Laere, S. Vervaeke & I. Surmont Yvoir, CU Mont Godinne Y. Glupczynski MIC by Microdilution (EUCAST) : Penicillin (PN) Amoxicillin (AM) Cefuroxime (CR) Ciprofloxacin (CI) Levofloxacin (LV) Moxifloxacin (MX) Erythromycin (ER) Telithromycin (TL) Tetracycline (TC) Gent Mons Haine-St.Paul Antwerpen Bonheiden Brussel Montigniesle-Tilleul Leuven Yvoir Hasselt Data on age, origin, sample, type of patient (H/A), gender. Liège Marche-en- Famenne Arlon S. pneumoniae. Resistance Follow-up. 1995-214
RESISTANCE RATES (%) FOR β-lactams % 25 2 15 1 5 19.8 15.1 17. 12.11 12.1 7.9 64 6.4 12.3 13.6 8. 9.8 PEN AMX CRX 1.7 5.6 9.2 7.8 3.5 14.5 17.9 16. 14.6 1.3 12.5 9.2 7.1 77 7.7 1995 95 1997 97 1999 21 1 23 3 24 4 25 5 26 6 27 7 28 8 29 9 21 211 212 213 214 S. pneumoniae. Resistance Follow-up. 1995-214
RESISTANCE RATES FOR β-lactams Evolution of Penicillin Non-susceptibility (I+R) 25 19.8 2 17.9 **** **** 15.2 16. 15 12.8 14.5 *** 1.4 1 1.1 9.2 5 21 23 24 25 26 27 28 29 21 211 212 213 214 S. pneumoniae. Resistance Follow-up. 1995-214
RESISTANCE RATES FOR β-lactams 25 Penicillin Non-susceptibility rates and type of treatment in pneumonia following EUCAST 2 15 1 5 1995 1997 1999 21 23 24 25 26 27 28 29 21 211 212 213 214 Infections meningitis 1.2g x 4 2.4g x 4 or 1.2g x 6 2.4g x 6 Infection/θ Regimen Breakpoint S NS Infections meningitis.6.12 Pneumonia: 1.2g X 4.5 1 2.4g X 4 or 1.2g X 6 1 2 2.4g X 6 2 4 S. pneumoniae. Resistance Follow-up. 1995-214
RESISTANCE RATES FOR β-lactams 14 12 12.3 Evolution of Amoxicillin Non-susceptibility (IR) 1 8 6 4 2 **** 8. 9.8 6.5 4.6 3.5 46 4.6 *** 7.1 9.2 ** 7.7 1999 21 23 24 25 26 27 28 29 21 211 212 213 214 S. pneumoniae. Resistance Follow-up. 1995-214
RESISTANCE RATES FOR β-lactams Evolution of Cefuroxime Non-susceptibility (CRX) 18 16 14 12 1 17. 13.6 **** 11.9 97 9.7 12.5 *** 14.6 1.3 8 6 9.2 7.8 8.7 4 2 21 23 24 25 26 27 28 29 21 211 212 213 214 S. pneumoniae. Resistance Follow-up. 1995-214
RESISTANCE RATES FOR β-lactams 25 2 15 1 5 Evolution of non-susceptibility of CRX and CRX-ax (EUCAST) 2.8 19. 14.8 15.2 17. 13.2 15.4 8.6 12.7 9.4 9.7 7.9 7.8 18.2 14.6 13.1 1.3 1995 1997 1999 21 23 24 25 26 27 28 29 21 211 212 213 214 CRX CRX-ax S. pneumoniae. Resistance Follow-up. 1995-214
RESISTANCE RATES FOR β-lactams S. pneumoniae: Serotypes PCV13 1 3 4 5 6A 6B 7F 9V 14 18C 19A 19F 23F 212 56.9 % 5.9 2. 9.8 35.3 3.9 213 53. % 3. 1.5 1.5 1.5 1.6 16.7 15.2 3. 214 4. % 3. 1. %PENNS PEN-NS in PCV13 isolates from Adults 212 79.3 % 213 91.4 % 214 95. % S. pneumoniae. Resistance Follow-up. 1995-214
RESISTANCE RATES (%) FOR FLUOROQUINOLONES 4 3.3 3 2.4 2.8 3.1 % 2 1 1.2 9.9.2.5 1995 1997 1999 21 23 24 25 26 27 28 29 21 211 212 213 214 LEV MOX.7 1..8.2 1.1.5.8.3 1.4.6.3 S. pneumoniae. Resistance Follow-up. 1995-214
RESISTANCE RATES (%) FOR MLS & TETRACYCLINE % 5 45 4 35 3 25 2 15 1 5 43.7 4.9 37.7 36.9 32.9 32.7 29.7 27.1 26.9 27.9 31.2 32.4 32. 29.3 25.8 24.8 25.9 26.3 2. 4.1 2.6 2.4.9.7 1.1 1.6 2.9 1995 1997 1999 21 23 24 25 26 27 28 29 21 211 212 213 214 ERY TEL TET S. pneumoniae. Resistance Follow-up. 1995-214
RESISTANCE and AGE 6 Age Distribution (SP214) 5 4 3 2 1-5 6-1 11-15 16-2 21-25 26-3 31-35 36-4 41-45 46-5 51-55 56-6 61-65 66-7 71-75 76-8 81-85 86-9 91-95 96-1 S. pneumoniae. Resistance Follow-up. 1995-214
RESISTANCE and AGE Mean age by region (SP214) 7 6 5 39.2 (N***) 62. (S****) 46.1 51.9 4 3 2 1 BRUSS NORTH SOUTH NAT Evolution of mean age and % of children ( 5y) 6 % 4 2 22.5 18.3 16.9 11.4 26.4 15.4 17.9 18.4 18.2 14.7 15.3 18.4 2.7 1 12.5 16.7 1995 1997 1999 21 23 24 25 26 27 28 29 21 211 212 213 214 %Ch 5y mean age S. pneumoniae. Resistance Follow-up. 1995-214
RESISTANCE and AGE Resistance rates: Childrens versus Adults (SP214) 4 35 3 25 2 15 1 5 29.3 22.2 2.66 14.3 16.5 38.6 27.7 27..8 Pen Lev Ery Tet IR Children Adults S. pneumoniae. Resistance Follow-up. 1995-214
RESISTANCE and AGE Non susceptibility rates (%) 1 for 4 indicator antibiotics in children ( 5 y) and adults PENICILLIN LEVOFLOXACIN ERYTHROMYCIN TETRACYCLINE NS-ISOLATES 2-5y 5y Adults -5y 5y Adults -5y 5y Adults -5y 5y Adults -5y 5y Adults 1995 25.8** 7.5 25.8 18.7 29. 26.2 41.9 32.7 1997 13.3 11.6 1.6 46.7** 24.8 33.3 28.7 53.3 34.9 1999 23.1 13.8.8 2.4 53.9** 29.3 34.6 24.4 61.5 43.9 21 25. 19.4 3.6 3.2 35.7 27.3 5. 42.6 6.7 5. 23 11.7 15.6 1.9 3.7 29.1 24.3 46.6 38.3 55.3 47.6 24 15.4 14.8 3.1 2.9 47.7**** 2. 4.*** 24.3 58.5*** 35.1 25 2. 13.8 1.3.6 4.* 28.5 35. 28.5 5. 4.6 26 12.7 12.5.6 55.7**** 33.9 44.3*** 27.9 58.2**** 37.6 27 14.7 11.8 1.2 4. 29.4 35.7 27.2 45.3 35.9 28 15.2 11.4.8 43.9*** 27.3 31.8 23.8 47.* 32.4 29 19.** 8.7.9 46. 4.1 36.5 3.2 49.2 43.1 21 11.8 8.7 1. 42.6* 3.2 33.8 29.9 47.1 36.8 211 19.7*** 7.8 1.4 43.4* 3. 42.1 3.7 47.4 36. 212 25.7* 13.3 3.6 37.1 29.5 37.1 27.3 42.9 38. 213 15.2 18.3 1.6 37. 36.6 3.4 32.2 39.1 43.2 214 13.5 16.5.8 23.1 29.3 21.2 27.7 26.9 38.6 1 Significant difference are indicated by an asterisk. *.5>P>.2; **.2>P>.1; ***.1>P>.1; ***P<.1 2 Isolates showing resistance to whichever of the indicator antibiotics S. pneumoniae. Resistance Follow-up. 1995-214
RESISTANCE and AGE NS-rates mostly CHILD > ADULT; except FQ 6 Erythromycin Resistance following age 53.8 55.7 5 46.7 47.7 43.9 46. 42.6 43.4 37.1 37. % 4 3 2 35.7 3.3 25.8 28.7 24.829.3 24. 18.7 2. 28.5 4. 33.9 4. 29.4 27.3 4.1 36.6 3.2 3. 29.5 29.3 23.1 1 1995 1997** 1999** 21 23 24**** 25* 26**** 27 28*** 29 21* 211* 212 213 214-5y Adults S. pneumoniae. Resistance Follow-up. 1995-214
RESISTANCE and REGION Distribution of isolates following Region (SP214) 6 51.9 5 39.8 4 % 3 2 8.3 1 Brussels North South 45 Resistance rates by region (SP214) 42. Brussels North South % 4 35 3 25 2 15 1 21. 23.4 14.8 34.6 34. 34.7 7.7 21.8 77 7.7 7.7 North South Bruss 5 1.2 Pen* Lev Ery Tet IR S. pneumoniae. Resistance Follow-up. 1995-214
RESISTANCE and REGION 23 24 25 26 27 28 29 21 211 212 213 214 PEN S S S*** S** S S S S S**** S S N LEV S* S N N S N N N S N* S S ERY S* S*** S*** S S S S** S**** S**** S*** S*** S*** TET S S S S S S S*** S*** S* S S S**** IR S* S*** S**** S S S S** S**** S*** S* S* S*** S. pneumoniae. Resistance Follow-up. 1995-214
RESISTANCE RATES (%) in CAP and AECB isolates* 45 4 CAP (%) AECB (%) 35 3 25 2 15 1 5 PEN AMX CRX CRX-ax LEV MOX ERY TEL TET IR *Period 26-214; compiled data S. pneumoniae. Resistance Follow-up. 1995-214
MIC Distributions of PEN G % 7 1995 R-EUCAST 1997 6 1999 5 21 23 4 24 25 3 2 1, 1, 2, 3, 6,1 12,2 25,5 1 2 4 8 26 27 28 29 21 211 212 213 214 Bimodal Distribution S. pneumoniae. Resistance Follow-up. MIC Distribution 1995-214
MIC Distributions of PEN G Evolution of the MIC5 in PEN-S and PEN-NS isolates 1995 1997 1999 21 23 24 25 26 27 28 29 21 211 212 213 214.4.8.15.3.6.12.25.5 1 2 4 PEN-S PEN-I PEN-R S. pneumoniae. Resistance Follow-up. MIC Distribution. 1995-214
MIC Distributions of FQ % 7 1995 6 5 4 3 2 1,3,6,12,25,5 1 2 NS 4 8 16 1997 1999 21 23 24 25 26 27 28 29 21 211 212 213 214 % 6 5 4 3 2 1,1,2,3,6,12,25,5 NS 1 2 4 LEV MOX S. pneumoniae. Resistance Follow-up. MIC Distribution 1995-214
MIC Distributions of FQ Evolution of the MIC5 in LEV-S and LEV-NS isolates.3.6.12.25.5 1 2 4 8 16 1995 1997 2 1999 4 21 8 1 23 7 6 24 11 1 25 2 1 26 2 27 1 3 28 1 2 29 1 2 21 2 1 211 2 2 212 1 1 Evolution of the MIC5 in MOX-S and MOX-R isolates 213 3 1 1.15.3.6.12.25.5 1 2 4 8 214 1 1 1995 LEV-S LEV-NS 1997 1999 2 21 2 1 23 1 1 24 1 25 1 26 1 27 2 1 28 1 1 29 1 21 1 211 2 212 1 213 3 214 1 MOX-S MOX-NS S. pneumoniae. Resistance Follow-up. MIC Distribution. 1995-214
Cross-Resistance Degree of activity (%) of the indicated antimicrobials on S. pneumoniae isolates non-susceptible (NS) to the various compounds (1995-214) %Susceptible PEN-NS AMX-NS CRX-NS LEV-NS MOX-NS ERY-NS TEL-NS TET-NS PEN -.3 65.8 58.3 69.1 45.8 71.2 AMX 46.7-36.5 79.7 62.5 82.2 64.9 84. CRX 17.7.5-68.4 58.3 72.7 49.4 74.9 LEV 96.5 95.9 95.9-98. 92.8 98. MOX 98.6 97.7 98.2 69.6-99.5 96.4 99.4 ERY 32.7 22.7 23.22 55.7 62.5-19.8 TEL 93. 9.4 92.1 9.8 84.2 94.6-94.7 TET 34.2 3.9 3.5 57. 58.3 21.1 8.4 - Degree exceeding 9% Degree exceeding 95% S. pneumoniae. Resistance Follow-up. 1995-214
Conclusions Decreasing Rates of Non Susceptibility (NS) in period 21-21 Significant increase of PEN-, AMX-, CRX-NS since 211. PEN-NS isolates: 4-57% of isolates comprised in PCV13 Especially in adults ( 8%) Decrease RR in 214 In general Rate of NS: Children > Adults (not always significant) Regional Differences can be found Rate of NS AECB > CAP (not significant) Cross-Resistance: important %S to MOX, LEV, TEL S. pneumoniae. Resistance Follow-up. 1995-214