Streptococcus pneumoniae

Transcription

1 Streptococcus pneumoniae EPIDEMIOLOGY AND PREVENTION 2^4. November 2007 Prof. Dr. Kathrin Mühlemann Klinik und Poliklinik für Infektionskrankheiten Universität Bern, INSELSPITAL

2 S. pneumoniae: epidemiology and prevention in Switzerland Incidence, risk factors Antibiotic resistance Aplenia Vaccines Outlook 2

3 Streptococcus pneumoniae A CHAMPION AMONG HUMAN PATHOGENS Acute otitis media Bact. pneumonia Bact. meningitis 1. Pneumococcus 1. Pneumococcus 1. Pneumococcus 2. H. influenzae 2. Atypical bacteria 2. Meningococcus 3. M. catharralis 3. H. influenzae 3. Other 3

4 Streptococcus pneumoniae gram + diplococcus encapsulated VIRULENCE Capsule Vaccine H 2 O 2 Flora etc., etc. EVOLUTION transformable DNA capsule switch AB resistance reservoir nasopharynx Colonised (%) droplet 1 2 m C a se s (n) > Age (Years) Age (years) > 89 4

5 Invasive pneumococcal infections before PCV7 Cases per population per year Cases / 10E5 per year RISK FACTORS: 200 age (young, old) 160 crowding (day care) <12 Mo <24 Mo resp. viral infection >64 J season smoking immunosuppress. (HIV, etc) 0 asplenia NOT vaccinated PCV7 = 7 valent, conjugated pneumococcal vaccine BAG Suppl. XVII 2005; Whitney C et al. NEJM 2003;348:1737 5

6 Seasonal variation of RSV and influenza activity and invasive S. pneumoniae infections (IPD) children: RSV and IPD r = 0.578, p=0.002 adults: RSV+flu and IPD r = 0.481, p=0.013 Watson M et al. Clin Infect Dis

7 Respiratory virus and S. pneumoniae Virus* PAF R adherence of S. pneumoniae (* shown for rhinovirus, RSV) Influenza neuramindase liberates host receptors adherence of S. pneumoniae PAF R = platelet activating factor receptor Ishizuka S et al. J Infect Dis 2004;188: 1928; McCullers JA, Bartmess KC. J Infect Dis 2003;187:1000 7

8 Antibiotic resistance 8

9 S. pneumoniae resistance prevalence % Penicillin, I+R Ceftriaxon, I Penicillin, R OTHER WEST Age, yrs Sentinel Network,

10 Trends of non invasive S. pneumoniae non susceptible to penicillin in Switzerland % Penicillin non susceptible Other West All Sentinel Network / Mühlemann K unpublished 10

11 S. pneumoniae resistance prevalence % Macrolide TMP SMX OTHER WEST Age, yrs Sentinel Network,

12 S. pneumoniae antibiotic resistance and antibotic consumption Switzerland Switzerland Albrich W et al. Emerg Infect Dis 2004; Filippini M et al. Health Policy 2006; Kronenberg A et al. J Clin Microbiol

13 Risk factors for antibiotic resistance in Switzerland antibiotic sales outpatients >1 AOM last 12 mo West Other Day care West Other Antibiotics last 2 mo West Other Percent Kronenberg A et al. J Clin Microbiol; Mühlemann K. J Infect Dis

14 Respiratory virus and S. pneumoniae >7d risk of PNSP carriage 4% per additional day of antibiotic Selection pressure penicillin<cephalosporine po clarithromycin<azithromycin Nasrin D et al. BMJ 2002; Vanderkooi OG et al. Clin Infect Dis

15 S. pneumoniae resistance penicillin versus amoxicillin CLSI breakpoint infection outside CNS CNS infection Intermediate resistant Intermediate resistant Brueggeman A et al. J Clin Microbiol 2001;39:267 15

16 S. pneumoniae resistance amoxillin po versus cefuroxime axetil Amoxicillin Brueggeman A et al. J Clin Microbiol 2001;39:267 16

17 PK/PD S. pneumoniae Time > MIC = >40 50% dose interval 40% 50% Regimen MIC Amoxicillin 500 mg q8 po Cefaclor 500 mg q8 po 8 16 Cefuroxim 500 mg q12 po Cefprozil 500 mg q12 po Loracarbef 400 mg q12 po 2 16 Cefpodox. 200 mg q12 po Ceftriaxon 1g q24 iv Craig W. Diagn Microbiol Infect Dis 1996 und CID 1999 Time > MIC % dose interval 100% 17

18 S. pneumoniae and asplenia long term antibiotic prophylaxis for children 0 5 years Penicillin 2x 125 mg/d (=2x 0.2 Mio IE) OR Amoxicillin 1x 20 mg/kg/d po >5 years Penicillin 2x 250 mg/d (=2x 0.4 Mio IE) OR Amoxicillin 1x 20 mg/kg/d po Start immediately Duration (?): First 5 years of of life First 3 years after splenectomy (evtl. to adolescence??) Penicillin intolerance switch to emergency therapy Heiniger U et al. BAG Bulletin

19 S. pneumoniae and asplenia emergency therapy for children Amoxicillin / clavul. acid mg/kg/d in 3 doses po Penicillin intolerance: Ceprozil 3x 30 mg/kg/d po Clarithromycin 2x 7.5 mg/kg/d po Clindamycin 3x 10 mg/kg/d po Heiniger U et al. BAG Bulletin

20 Heiniger U et al. BAG Bulletin

21 Vaccine 21

22 7 valent conjugated pneumococcal polysaccharide vaccine (PCV7) USA Highly (>90%) protective against invasive infection in <2 years olds Vaccine types colonisation Herd immunity Children <2 years of age Children >2 years of age, adults Black S et al. Ped Infect Dis J 2000; Baclk S et al. Pediatr Infect Dis 2002; Kyaw MH et al. NEJM

23 7 valent conjugated pneumococcal polysaccharide vaccine (PCV7) USA Based on Based on Grijalva CG et al. Lnacet

24 PCV7 recommendation in Switzerland Nov 2005: May 2006: Aug 2006: «ergänzende/supplementaire» vaccine all infants 2, 4, 3, mo two dose schedule: 2, 4, 12 mo reimbursement BAG Bulletin 2006;40:92 / 24

25 PCV7 recommendation Asplenia in Switzerland children at risk Sickle cell anemia Immunosuppression (congenital, iatrogenic, HIV) Chronic cardio pulmonary disease Chronic renal insufficiency, nephrotic syndrome Cochlear implant Skull malformation, CSF fistula Repeated boosting in 24 mo old: persistent high risk OR inv. pneumococcal infection monitor type spec. antibody titers Heiniger U et al. BAG Bulletin ; BAG Bulletin 2005; ; 25

26 S. pneumoniae capsular serotypes >90 different serotypes, different prevalence yrs 0 1 yrs B 23F 19F 6A 19A 18C 7F 9V nt 4 5 Serotype >64 yrs yrs National Reference Center for Invasive Pneumococci, Data

27 S. pneumoniae capsular serotypes 7 valent conjugate vaccine 6B, 9V, 14, 19F, 23F, 4, 18C Associated with resistance 6B, 9V, 14, 19F, 23F * B 23F 19F 6A 19A 18C 7F 9V nt 4 5 Serotype * * ** * 65% >64 yrs National Reference Center for Invasive Pneumococci, Data yrs yrs 0 1 yrs PCV7 50% 35% 39% 27

28 Invasive pneumococcal infections in Switzerland children <5 years old Per year (n) Age (y) Total Lethal Meningitis Pneumonia Sepsis Pneumonia (all) < < > ~ cases of acute otitis media (AOM) < 5 years of age BAG Suppl. XVII

29 S. pneumoniae epidemiology with PCV7 data from Switzerland % vaccinated with PCV Sentinel Surveillance for Non invasive Pneumococci 29

30 S. pneumoniae epidemiology with PCV7 data from Switzerland Age 0 1 years Cases (n) * 0 Jan Feb March April May June July Aug Sept Oct Nov Dec National Reference Centre for Invasive Pneumococci 30

31 S. pneumoniae epidemiology with PCV7 data from Switzerland Age 2 4 years * Cases (n) Jan Feb March April May June July Aug Sept Oct Nov Dec National Reference Centre for Invasive Pneumococci 31

32 S. pneumoniae epidemiology with PCV7 data from Switzerland Age >64 years Cases (n) Jan Feb March April May June July Aug Sept Oct Nov Dec National Reference Centre for Invasive Pneumococci 32

33 S. pneumoniae epidemiology with PCV7 data from Switzerland PCV7 serotypes % > age (yrs) National Reference Centre for Invasive Pneumococci 33

34 S. pneumoniae epidemiology with PCV7 serotype redistribution etc. relative of invasive pneumococcal infections by non vaccine serotypes more pronounced in HIV infected (temporary) decrease in resistance prevalence emergence of specific serotypes/clones: 19A / ST199 correlation versus association? influence on carriage of S. aureus, H. influenzae? 34

35 S. pneumoniae epidemiology with PCV7 and serotype redistribution Whitney CG et al. Lancet

36 S. pneumoniae epidemiology with PCV7 and serotype redistribution Children <2 years of age in Alaska Singleton RJ et al. JAMA

37 S. pneumoniae capsular serotypes 7 valent conjugate vaccine 6B, 9V, 14, 19F, 23F, 4, 18C * B 23F 19F 6A 19A 18C 7F 9V nt 4 5 Serotype * * ** * 65% >64 yrs National Reference Center for Invasive Pneumococci, Data yrs yrs 0 1 yrs PCV7 50% 35% 39% 37

38 Rückgang der Pneumokokken Resistenz durch den Einfluss des 7 valenten Konjugatimpfstoffs? Kyaw MH et al. NEJM

39 S. pneumoniae capsular serotypes 7 valent conjugate vaccine 6B, 9V, 14, 19F, 23F, 4, 18C 10 valent: + 1, 5, 7F 13 valent: ++ 3, 6A, 19A * B 23F 19F 6A 19A 18C 7F 9V nt 4 5 Serotype * * ** * * ** * 0 1 yrs 65% >64 yrs National Reference Center for Invasive Pneumococci, Data yrs yrs PCV7 50% 35% 39% PCV10 70% 70% 53% 50% PCV13 84% 84% 68% 69% 39

40 THANK YOU!! 40

41 S. pneumoniae resistance penicillin versus ceftriaxon CLSI breakpoint infection outside CNS CNS infection Brueggeman A et al. J Clin Microbiol 2001;39:267 41

42 Serotyp 19A wird «prominent» Pai et al. J Infect Dis