Multi-drug Resistant Serotype 19A Pneumococci in Toronto

Transcription

1 TML Lab Rounds January 17, 2008 Multi-drug Resistant Serotype 19A Pneumococci in Toronto The Role of the Microbiology Lab Susan M. Poutanen, MD, MPH, FRCPC Microbiologist/ID Consultant, TML/MSH Assistant Professor, U. of Toronto

2 Outline 1. To review the impact of Prevnar on resistant pneumococci 2. To review the emergence of multi-drug resistant serotype 19A pneumococci in recent years 3. To review the role of the microbiology laboratory in the surveillance of multi-drug resistant pneumococci

3 Case

4 Case October 10, 2007 Gram-positive diplococci identified from 2/2 blood cultures from client hospital

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7 Case (continued) October 10, 2007 Identified as Streptococcus pneumoniae CSF cultures also noted to be positive for the same organism Susceptibility testing completed

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11 MICs by Broth Microdilution The strain was resistant to: penicillin (MIC = 4 mg/l) amoxicillin (MIC = 8 mg/l) cefprozil (MIC > 16 mg/l) cefuroxime (MIC = 16 mg/l) ceftriaxone (MIC = 2 mg/l) meropenem (MIC = 1 mg/l by Etest) erythromycin (MIC > 32 mg/l) clindamycin (MIC > 16 mg/l) trimethoprim-sulfamethoxazole (MIC = 8/152 mg/l) tetracycline (MIC > 8 mg/l)

12 MICs by Broth Microdilution The strain was susceptible to: vancomycin (MIC 0.5 mg/l) levofloxacin (MIC 0.25 mg/l) rifampin (36 mm by disk diffusion) telithromycin (MIC = 0.5 mg/l)

13 Case (continued) Physician notified of results Lab updated that patient was a 14-month-old previously healthy fully vaccinated child (including Prevnar ) from Toronto with no travel history The isolate was serotyped in-house using antisera from Statens Serum Institut and confirmed by the National Centre for Streptococcus in Edmonton Noted to be a non-vaccine serotype: 19A

14 Pichichero et al. JAMA 2007;298(15):

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18 Prevnar Pneumococcal Vaccine

19 Prevnar Pneumococcal conjugate vaccine Polysaccharide antigens from 7 capsular serotypes conjugated to a carrier protein Serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F Most prevalent, most resistant serotypes Cross-protection expected (e.g. 6A, 19A)

20 Prevnar Introduced in the US in 2000 Introduced in Canada in 2001

21 Kyaw et al. NEJM 2006;354:

22 Kyaw et al. NEJM 2006;354:

23 Zhou et al. Arch Pediatr Adolesc Med 2007;161(12):

24 Universal program started in BC in Sept 2003 Paulus et al. CCDR 2006;32(14):

25 Emergence of Nonvaccine Serotype Pneumococci

26 Hicks et al. JID 2007;196: Rates of invasive pneumococcal disease, <5 years old

27 Hicks et al. JID 2007;196: Rates of invasive pneumococcal disease, <5 years old

28 Hicks et al. JID 2007;196: Rates of invasive pneumococcal disease, 65 years old

29 Hicks et al. JID 2007;196: Rates of invasive pneumococcal disease, 65 years old

30 Singleton et al. JAMA 2007;297:

31 Singleton et al. JAMA 2007;297:

32 Emergence of 19A

33 Singleton et al. JAMA 2007;297: Invasive pneumococcal disease, < 2 years

34 Singleton et al. JAMA 2007;297:

35 Singleton et al. JAMA 2007;297:

36 Farrell et al. Pediatr Infect Dis J 2007;26:

37 Resistance among Nonvaccine Serotype Respiratory Pneumococci Antimicrobial Year 1 Year 4 Pen I 20% 32% Amox-clav R 1% 6% Ery R 21% 32% >=2 drugs R 25% 32% Farrell et al. Pediatr Infect Dis J 2007;26:

38 Emergence of MDR Serotype 19A Pneumococci

39 Pichichero et al. JAMA 2007;298(15):

40 Study Prospective cohort study children with acute otitis media who had received Prevnar Tympanocentesis performed to determine serotypes and susceptibility of S. pneumoniae causing acute otitis media Pichichero et al. JAMA 2007;298(15):

41 Anatomy of the Ear

42 Physician s Viewpoint

43 Results Of the 212 cases, 59 (28%) were due to S. pneumoniae 9 cases were due to MDR-19A S. pneumoniae resistant to all antibiotics approved for use in children with otitis media All were treated successfully with levofloxacin or tympanostomy tube insertion

44 Hsu et al. MMWR 2007;56(41):

45 Study Statewide laboratory- and population-based surveillance of invasive pneumococcal disease (IPD) among children in Massachusetts Serotyping and susceptibility testing completed to determine trend in IPD post introduction of Prevnar Hsu et al. MMWR 2007;56(41):

46 Results IPD Cases A 10% 11% 29% 39% 41% MDR 19A 0% 1% 4% 10% 17% MDR overall 8% 10% 9% 14% 22% Hsu et al. MMWR 2007;56(41):

47 Results IPD Cases A 10% 11% 29% 39% 41% MDR 19A 0% 1% 4% 10% 17% MDR overall 8% 10% 9% 14% 22% Hsu et al. MMWR 2007;56(41):

48 Results Increasing proportion of IPD caused by 19A 19A most common cause of IPD Increasing resistance of 19A 19A most resistant serotype Hsu et al. MMWR 2007;56(41):

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51 Canadian Data IPD due to MDR serotype 19A S. pneumoniae has been detected in Toronto since 2004 Approximately 20 cases known to date in adults and children TIBDN & CBSN (Personal Communication, A. McGeer)

52 Results IPD Cases A 10% 11% 29% 39% 41% MDR 19A 0% 1% 4% 10% 17% MDR overall 8% 10% 9% 14% 22% Hsu et al. MMWR 2007;56(41):

53 Causes

54 Why Increasing MDR 19A SPN? Vaccine selective pressure Immunologic selection Increase colonization of non-vaccine type SPN in vaccinated and unvaccinated children post Prevnar (O Brien et al) Antimicrobial selective pressure Serotype switching O-Brien et al. JID 2007;196:

55 Solutions

56 How Can We Decrease MDR 19A? Reduce vaccine selective pressure by expanding vaccine to cover 19A 13-valent vaccine (including 19A) clinical trials are under way in the US Reduce antimicrobial selective pressure

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58 How Can We Decrease MDR 19A? Encourage flu vaccination Influenza infection predisposing factor for severe pneumococcal pneumonia (O Brien et al) Encourage neuraminidase (NA) inhibitor treatment of influenza Influenza NA may potentiate development of pneumococcal pneumonia by stripping away sialic acid and exposing pneumococcal receptors (McCullers et al) O-Brien et al. CID 2000;30:784-9; McCullers et al. JID 2003;187:1000-9

59 How Will We Know These Interventions are Working? The Role of the Microbiology Lab All cases of IPD are reportable to Public Health Serotyping of pneumococci is not mandatory Approximately 1000 cases of IPD in Ontario/year Only approximately 100 isolates are serotyped by the Central Public Health Laboratory No MDR 19A noted by the province as of yet

60 How Will We Know These Interventions are Working? The Role of the Microbiology Lab (cont d) Province-wide laboratory-based surveillance for IPD should be initiated to increase understanding of the changes in serotypes and antimicrobial susceptibility in invasive pneumococci Proposed to MOHLTC

61 PNEUMOCOCC US 19 A