Drug resistant Gram positives. Dr Subramanian S MD MNAMS AB Infectious Diseases Infectious Diseases Consultant Global Health City, Chennai

Transcription

1 Drug resistant Gram positives Dr Subramanian S MD MNAMS AB Infectious Diseases Infectious Diseases Consultant Global Health City, Chennai

2 Flash news! Carbapenem resistant Gram negatives! Vancomycin resistant Staph! Ceftriaxone resistant gonococcus! MDR tuberculosis Drug resistant HIV! Fluconazole resistant Candida!

3 Why? Lack of suspicion and identification Inappropriate agent or inadequate dosing Advances in microbial resistance Abuse of drugs over the counter and in veterinary setting Dry drug pipeline

4 Where are Gram pos infections? Skin and soft tissue infections Dental and ENT infections Pulmonary infections Osteomyelitis Septic arthritis Endocarditis Meningitis

5 Gram positives! 57 year old with squamous cell cancer of oesophagus presented with fever, cough and chills. X ray confirms pneumonia. Patient dies of septic shock in 3 hours and blood cultures grow GPC 32 year old alcohol abuser with liver disease presents with fever, and altered sensorium. Encephalopathy is suspected. After blood cultures, antibiotics are started. Blood culture shows GPC, but he dies inspite of antibiotics. 80 year old healthy male has lunch at 2 pm. At 4 pm, he is aphasic. He deteriorates quickly, and no infarct is seen on scan. CSF shows GPC. He is improving on antibiotics.

6 Where is the disease??

7 Pneumococcal disease

8

9 CAP in Indian Adults Prevalence of S.pneumoniae CAP Study Details Total CAP Cases (Adult) Cases with Confirmed Etiology (n) S.pneumoniae +ve CAP (% of n) 2009; Lourdes hosp, Kerela % KIMS, Bengaluru % PD Hinduja hosp & BYL Nair hosp, Mumbai % AMCH, Bijapur % BMCRI, Bangalore % SKIMS, Srinagar % CMC, Ludhiana % IGMCH, Shimla % 1. Menon RU et al. J Fam Med Primary Care 2013;2: Mythri S et al. IOSR-JDMS.2013;12(2): Dagaonkar et al. Am J Respir Crit Care Med. 2012;185:A6060 (poster). 4. Abdullah BB et al. ISRN Pulmonology, Ramamurthy et al. JEMDS. 2013;2(12): Shah BA et al. Lung India. 2010;27(2): Oberoi et al. JK Science. 2006;8(2): Bansal S et al. Indian J Chest Dis Allied Sci. 2004;46 :17-22.

10 Acute Bacterial Meningitis (Community) Prevalence of S.pneumoniae ABM Mani R et al. Indian J Med Microbiol Apr;25(2):

11 Pneumococcal disease incidence

12 Pneumococcal mortality

13 Disease specific mortality

14 Co-infection: Influenza Virus and S.pneumoniae Co-infection Impacts Disease Severity S. Pneumoniae +ve: 125 times increased odds of severe influenza (95% CI: ; p<0.0001) Palacios G, Hornig M, Cisterna D et al. PLoS One Dec 31;4(12):e8540.

15 Pneumococcus in India Mostly suffering from denial! Estimated 136,000 deaths in under 5 in year 2005; 106 per 100,000 Western countries have axed this with vaccination Drug resistance unheard of a decade ago Emerging studies show more resistance than earlier!

16 Has PPV induced a sizeable impact on IPD in the US? Has PPV induced a sizeable impact on IPD? Cases/100,000 population 120 PCV7 introduced* Age group < PPV23 in use since 1987 Year Pilishvili T et al. J Infect Dis. 2010;201:32-41.

17 Quinolone resistance in S.pneumoniae in Canada Chen et al NEJM 1999

18 Restriction policy can work Heavy macrolide use in 80s in Finland Erythromycin resistant S.pneumoniae rose from 8% to 13% High use regions had high resistance Education on this done NEJM 1997;337

19 Reduction in resistance

20 S. Pneumoniae Antimicrobial Resistance in India Study ANSORP 1 ( ) Shariff et al 2 ( ) Molander et al 3 ( ) Antibiotic S % I % R % S % I % R % S % I % R % Penicillin Erythromycin Ceftriaxone Ciprofloxacin NA NA Cotrimoxazol e Kim SH et al. Antimicrob Agents Chemother Mar;56(3): Shariff M et al. J Infect Dev Ctries Feb 15;7(2): Molander V et al. BMC Infect Dis Nov 9;13(1):532.

21 Drug resistance in SP Study Penicillin non susceptibility IBIS % BMC ID % IJMR % Penicillin resistance is an independent and powerful predictor of mortality in patients with S.pneumoniae infection.

22 SSTI Cellulitis, folliculitis, furuncle, carbuncle, necrotizing fasciitis etc Most are due to Staph and Strep Gram negs in diabetic foot, post op, bites, penetrating injuries etc

23 Nosocomial Pathogens By Infection Type Pneumonia UTI BSI SSI S. Aureus 19% 2%. 16% 20% Coag (-) staph 2% 4% 31% 14% Enterococcus 2% 16% 9% 12% Pseudomonas 17% 11% 3% 8% Other gram (-) 29% 45% 17% 23% C. albicans <5% 8% 5% 3% Jernigan, J. Cecil s Textbook of Medicine

24 Proportion of SSTIs (%) Causes of SSTIs: SENTRY programme Staphylococcus aureus is the leading cause of SSTIs worldwide S. aureus P. aeruginosa E. coli Enterococcus spp. Enterobacter spp. β-streptococcus CoNS Klebsiella spp Europe North America SENTRY is a surveillance programme which evaluated over isolates over 7 year period in Europe, North America and Latin America Moet GJ et al. Diagn Microbiol Infect Dis 2007;57:7 13

25 Shifting epidemiology of serious infections SCOPE surveillance study Nosocomial bloodstream infections & mortality due to S. aureus Wisplinghoff H et al. Clin Infect Dis 2004;39:

26 Resistant isolates (%) The MRSA threat MRSA isolates among ICU patients in the US 1 MRSA isolates from bacteraemia patients in England and Wales US England and Wales Year Centers for Disease Control and Prevention. National Nosocomial Infections Surveillance System. MRSA among ICU patients, Johnson AP et al. J Antimicrob Chemother 2005;56:

27 The MRSA threat Indian Scenario Of the 739 cultures of S. aureus, 235 (32%) has been found to be multiply resistant with the individual figures of resistance being 27% - Mumbai 42.5% - Delhi & 47% - Bangalore MRSA is emerging to be a significant problem pathogen - Journal of Post. Grad. Med. 1996

28 Indian data on MRSA INSAR 2013 (2008-9) Study Outpatient Ward ICU 28% 46% 45% Bathalapalli % 71% Bangalore % 62% Most of these studies DO NOT report vanco MIC!!

29 The MRSA threat: India Risk factors for MRSA Srinivasan etal, Indian Journal of Medical Microbiology vol. 24, No. 3, 2006

30 Disease Manifestations due to Staphylococcus aureus Wounds Skin ulcers Pneumonia Intravenous line infections S. Antibiotic aureus selection Deep abscesses (Often with bacteraemia) Infective endocarditis Bacteraemia Osteomyelitis

31 MRSA : Treatment Options Vancomycin Teicoplanin Linezolid Daptomycin Tigecycline Dalfopristin/quinupristin Clindamycin Cotrimoxazole Investigational agents Telavancin (approvable) Dalbavancin Oritavancin PBP-2a targeted -lactams (ceftobiprole, ceftaroline)

32 Vancomycin reducing susceptibility A new clinical problem - VISA first reported in Japan in VRSA first reported in USA in 2002 Still a rare phenomenon and both have different resitance mechanisms Resistance has been related to increased Vancomycin use globally BUT in about 50% of cases Vancomycin was not used

33 Vancomycin MIC creep for MSSA and MRSA strains

34 Vancomycin Creeping MIC levels Increasing MIC for staphylococcus 2004) 3 - Shifting MIC - lesser than 0.5 µg/ml to >1 µg/ml (from 2000 to 1.Steinkraus G et al. J Antimicrob Chemother 2007;60: , Clin Microbiol Infect 2008; 14 (Suppl. 2): Soriano A et al. Clin Infect Dis 2008;46: data from US

35 Vancomycin Creeping MIC levels Increasing MIC for staphylococcus - Shifting MIC - lesser than 0.5 µg/ml to >1 µg/ml (from 2000 to 2004) 3 *Inappropriate therapy defined as empirical therapy to which the MRSA strain was resistant 1.Steinkraus G et al. J Antimicrob Chemother 2007;60: , Clin Microbiol Infect 2008; 14 (Suppl. 2): Soriano A et al. Clin Infect Dis 2008;46: data from US

36 No. of Days (median) Vancomycin Creeping MIC levels P= Low MIC (<1.5) High MIC (>1.5) 5 0 Length of stay (median) 2 fold increase in LOS with High Vanomycin MIC in MRSA infection fold increase in mean Hospital Cost with High Vanomycin MIC 2 1. T. P. Lodise et al Antimicrob agents chemother 2008, p Maclayton, D. O. et al, Clinical Ther. 28, Number 8, 2006 LOS = Length of Stay

37 Vancomycin Creeping MIC levels P= Low MIC (<1.5) High MIC (>1.5) Recurrence within 60 days Patients with higher Vancomycin MIC had a higher likelihood of recurrence 1 1. T. P. Lodise et al Antimicrobial agents and chemotherapy, Sept. 2008, p Maclayton, D. O. et al, Clinical Therapeutics/Volume 28, Number 8, 2006

38 High Vancomycin MIC and clinical failure

39 Log 10 CFU/g Bactericidal activity is rapid Time (h) Growth control Nafcillin Vancomycin Linezolid Cubicin Daptomycin Kern WV. Int J Clin Pract 2006;60:

40 Daptomycin efficacy in CRBSI P= Overall responce Vancomycin Daptomycin Daptomycin had improved overall response in more patients in comparison to vancomycin More that 3/4 th of the patients had clinical resolution within 2 nd day of Daptomycin therapy Anne-Marie Chaftari et al, Int J Antimicrob Agents :36 (2010)

41