1 / 50

Emerging ID issues: Drug Resistant Bacteria & Spreading Viruses

Emerging ID issues: Drug Resistant Bacteria & Spreading Viruses. Paul S. Sehdev, MD, MS, FACP, FIDSA Infectious Disease Consultants & The Traveler’s Clinic Providence St. Vincent’s Hospital October 14, 2011. Trends in S. aureus Disease. Emergence of MRSA Emergence of VISA

malise
Download Presentation

Emerging ID issues: Drug Resistant Bacteria & Spreading Viruses

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Emerging ID issues:Drug Resistant Bacteria & Spreading Viruses Paul S. Sehdev, MD, MS, FACP, FIDSA Infectious Disease Consultants & The Traveler’s Clinic Providence St. Vincent’s Hospital October 14, 2011

  2. Trends in S. aureus Disease • Emergence of MRSA • Emergence of VISA • Emergence of VRSA • Emergence of hVRSA • Community acquired MRSA • Resistance to new agents • Linezolid • Daptomycin

  3. Emergence of Methicillin Resistance • 1961: Methicillin introduced • 1962: MRSA identified • 1980: 5-10% hospital isolates MRSA • 1991: 25% hospital isolates MRSA • 2003: 64% isolates in NNISS Chambers. Emerg Inf Dis;7:178

  4. Methicillin Resistance: Mechanism • MecA gene • Encodes a low affinity PBP (PBP2a) • Affects all -lactam drugs • 5 types • Variable patterns of drug susceptibilities • Acquired from unknown locus • Mobile transposon-like element • Resistance profiles continue to change

  5. http://phsnet.phsor.org/laboratory/micro/antibiotics/QTR%204%202008PSVMCMRSA.pdfhttp://phsnet.phsor.org/laboratory/micro/antibiotics/QTR%204%202008PSVMCMRSA.pdf

  6. What is an Extended-Spectrum -Lactamase (ESBL)? • Variant of standard TEM & SHV -lactamases • Result of point mutations • Mutated -lactamase has extended spectrum • Degrades 3rd generation cephalosporins • Transmitted via plasmids • Over 150 ESBLs identified to date • E.Coli & K.pneumoniae Rice LB. Pharmacotherapy. 1999;19(8 Pt 2):120S.

  7. Molecular Basis of ESBLs Rice LB. Pharmacotherapy. 1999;19(8 Pt 2):120S.

  8. ESBLs Detection Methods: Inhibition by Clavulanic Acid

  9. Inoculum Effect in K. pneumoniae Isolates Containing ESBLs Thomson KS. Antimicrob Agents Chemother. 2001;45:3548.

  10. Therapy of ESBL Infections • Carbapenems best option • Cephalosporins: • In vitro & in vivo discordance • Failure of Ceftazidime in bacteremic patients • Reports of Ceftriaxone & Cefotaxime success • Meningitis and bacteremia • Few patients • Little data • Trimethoprim/ sulfamethoxazole • Aminoglycosides • Fluoroquinolones Wong-Beringer A. Pharmacotherapy 2001;21:583.

  11. This is Neisseria gonorrhea

  12. Resistance in N.gonorrhea • Emerged in 1970’s • Penicillin resistance • Tetracycline resistance • DOC in 1980’s became ciprofloxacin • Fluoroquinolone resistance emerged • AsiaHawaii Californiaeverywhere else • 2007, CDC recommended cephalopsorins • Ceftriaxone im or cefixime

  13. N. gonorrhea: Cephalosporin Resistance 2000-2010 www.cdc.gov/mmwr/preview/mmwrhtml/mm6026a2.htm?s_cid=mm6026a2_w#fig2

  14. New kid on the block:New Delhi metallo-ß-lactamase-1 (NDM-1) • 2009, first report • UTI after travel to India • Isolate was K. pneumoniae • Resistant to all beta-lactam drugs • E.coli possessing NDM-1 found in patient’s stool • 2010 USA • 3 cases with 3 different organisms • 2011 Cases on all continents • Except Antarctica & S. America

  15. NDM-1 • Encodes for broad spectrum B-lactamase • Resistant to all B-lactam drugs • Sensitive to tigecycline & colistin • Resides on a plasmid • Transferable between bacteria • Within a species • Across species • Prevalence rates • USA low • India 4% of enteric Gram-negative bacilli

  16. Why the easy spread?Horizontal transfer

  17. NDM-1: It’s in the water • Prevalence study from New Dehli, India • September-October 2010 • Sampled water • Seepage (puddles & rivulets) • Public tap water • 221 samples (171 seepage & 50 tap H2O • 51 of 171 (29%) & 2 of 50 (4%) positive • 11 different bacteria possessed • Including V. cholera & Shigella species • Huge implications for developing world • Worldwide interconnectedness makes further spread likely http://www.ncbi.nlm.nih.gov/pubmed/21478057

  18. Containing NDM-1 • This will NOT just go away! • Infection control is paramount • High index of suspicion • Contact isolation • Good hand hygiene • Active surveillance • Limiting broad spectrum antibiotic use • Reduces “pressure” that enables resistant bugs to thrive • Reserve active agents • Few (no?) new antibiotics in pipeline

  19. Chickungunya

  20. Chikungunya Background • 1st described in 1952 • Outbreaks of febrile polyarthritis • Makonde word • “that which contorts or bends up” • Virus was isolated in 1953 • Spread throughout South-Central Africa • Spread to Thailand in 1958 • Now, endemic in S. Asia • Indian Ocean outbreak ongoing since 2004

  21. Indian Ocean Outbreak Pialoux G, Lancet, 2007;7:319-27

  22. Epicurves Reunion & France Pialoux G, Lancet, 2007;7:319-27

  23. Clinical Manifestations • Primary infection features • Fever 86-100% • Arthralgias 96-100% • Hands, wrists & ankles • Headache 47% • Rash 40% • Secondary • Chronic polyarthralgia 5-10% • Persists for months to years • Mechanism for disease unknown • Mortality <1% Simon F, Med Clin N Am 2008;92:1323-43

  24. Clinical Manifestations Simon F, Med Clin N Am 2008;92:1323-43

  25. Making the Diagnosis Pialoux G, Lancet, 2007;7:319-27

  26. Treatment & Prevention • Supportive therapy • DEET to repel mosquitoes • Vaccine • Live attenuated vaccine candidate (TSI-GSD-218) • Phase II trials • Single dose vaccine • 98% developed neutralizing antibody at day 28 • 85% remained sero-positive at 52 weeks • Trials shelved in 2002 • Future uncertain Edelman R, Am J Trop Med Hyg 2000;62(6):681-5

  27. Dengue Viruses • Flavivirus • Single stranded, nonsegmented RNA virus • 4 distinct serotypes • Each serotype provides lifelong immunity • Infection does not confer cross protection • All can cause severe manifestations • Can be infected up to 4 times • Subsequent infections may be severe • Main reservoir is humans • Non-human primates may be infected

  28. Dengue Disease Burden • Most common arboviral disease • Endemic in 100 countries • 2.5 billion persons at risk • 100 million cases yearly • 250,000 cases of Dengue hemorrhagic fever • 25,000 deaths yearly

  29. Aedes Mosquitoes • Highly susceptible to Dengue infection • Preferred nourishment is human blood • Thrives in urban environments • Bites during daytime • Bite is nearly imperceptible • May bite several people to obtain a blood meal

  30. Spread & Distribution of Dengue http://www.who.int/csr/disease/dengue/impact/en/

  31. Dengue in Puerto Rico 2009-11

  32. Dengue Clinical Syndromes • Undifferentiated fever • Classic dengue fever • Severe Dengue • Dengue hemorrhagic fever • Dengue shock syndrome

  33. Classic Dengue Fever • Sudden onset fever • Headache & retro-orbital pain • Severe myalgia & arthralgia • “Break-bone fever” • Skin rash • Appears around time of defervescence • Mild hemorrhagic manifestations • Tourniquet tests • Laboratories • Leukopenia, lymphopenia & thromobocytopenia • Transaminitis

  34. Tourniquet Test Wilder-Smith A and Schwartz E. N Engl J Med 2005;353:924-932

  35. Chikungunya vs. Dengue

  36. Dengue Hemorrhagic Fever: CDC Case Definition • 4 criteria—must meet all • Fever • Hemorrhagic manifestations • Platelet count <100,000/mm3 • “Leaky capillaries” • Hematocrit >20% above baseline) • Low albumin • Pleural or other effusions

  37. Dengue Shock Syndrome • 4 criteria for DHF plus • Circulatory failure: • Rapid and weak pulse • Pulse pressure < 20 mm Hg • SBP <90 mmHg • Duration of shock is short • 12-24 hours • Supportive care only intervention • Morality ranges from 0.2%-20% • 2 deaths in USA from 1993-2000

  38. DHF Mechanism • Antibody mediated enhancement • Cross reacting Abs bind virus • They do no neutralize bound virus • Complexes bind Fc receptors • Replicate in dendritic cells & macrophages • Viral load is increased • Killer cells & T-cell are activated • “Cytokine storm” ensues • Endothelial damage & capillary leakage

  39. Wilder-Smith A and Schwartz E. N Engl J Med 2005;353:924-932

  40. Dengue Prevention • Insect precautions are mainstay • Vaccines • 2 candidates in phase 2-3 trials • Both live attenuated viruses • Both tetravalent vaccines • Immunogenic, but not reactogenic • Field trials in planning stages • Vector control • Must be multi-modal

  41. Sehdev P Clin Inf Dis 2002;35(9):1071–1072

  42. Yellow Fever • 1st outbreak in New World 1648 • Yet, thought to originate from Africa • Global epidemics • 1793: Philadelphia 10% population died • 1878: Mississippi Valley 100,000 cases • Sanitary measures reduced burden • Serendipitous • Vector was not known at time • Virus isolated in 1927 • Vaccine developed in 1928

  43. Yellow Fever Map 2007 http://www.cdc.gov/ncidod/dvbid/yellowfever/YF_GlobalMap.html

  44. Estimated Disease Burden • 200,000 cases per year • 30,000 deaths • Epidemic attack rates • 30 cases per 1,000 persons • Case fatality rates • 20-50% in endemic areas • Imported cases rare, but deadly • 6 cases USA & Europe 1996-2004 http://wwwn.cdc.gov/travel/yellowbook/ch4/yellow-fever.aspx

  45. YF Transmission Cycle Monath TP, Lancet ID 2001;1:11-20

  46. Stages of Yellow Fever Monath TP, Lancet ID 2001;1:11-20

  47. Diagnosis & Treatment • Mainstay is serology • Single positive IgM • Fourfold rise in IgG titer • PCR positive early (days 1-6) • But, not readily available • Culture is gold standard • Therapy is supportive • Ribavirin has been tried, but doesn’t work • Immunoglobulin not useful

  48. Yellow Fever Vaccine • Live, attenuated virus (17D strain) • 95% effective, 10 year protection • HA, fever & myalgia • Immediate hypersensitivity (1/131,000) • Vaccine associated neurotrophic disease • 16/23 case age < 9 months • Vaccine associated viscerotropic disease • 10 cases since 1996 • Contraindications • Egg allergy & age < 9 months MMWR 2002;51:RR-17

More Related