Nursing Infectious Diseases Topics. David H. Spach, MD Professor of Medicine Division of Infectious Diseases University of Washington, Seattle

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1 Nursing Infectious Diseases Topics David H. Spach, MD Professor of Medicine Division of Infectious Diseases University of Washington, Seattle

2 Clostridium difficile

3 Free Access Via Web Source: Cohen SH, et al. Infect Control Hosp Epidemiol. 2010:31:

4 Clostridium difficile-associated Diarrhea Pathogeneis Healthy Adult C. difficile Colonization Asymptomatic Colonization (carrier state) C. difficile diarrhea Incubation range 2 days to 6 weeks Source: Poutanen S, Simor AE. CMAJ. 2004;171:51-8.

5 Clostridium difficile-associated Diarrhea Pathogeneis Healthy Adult C. difficile Colonization Risk Factors Antibiotics Prolonged hospital stay Age > 65 Severe Illness GI Surgery Nasogastric tube Antacids Stool softeners

6 Clostridium difficile Associated Diarrhea Diagnostic Tests Stool culture for C. difficile - Most sensitive, but labor intensive and slow - High false-positive rate (culture nontoxigenic strains) Antigen Detection - Detects presence of C. difficile (not toxin) Toxin Genes: Molecular Tests (PCR) - Rapid detection of genes encoding Toxins - High sensitivity and specificity A B Toxin Detection: Tissue culture cytotoxic assay - Gold Standard but high cost and takes >48h Toxin Detection: Enzyme immunoassay - Detects toxins A and B A B

7 Clostridium difficile Associated Diarrhea Emergence of Hypervirulent Strain ( NAP1 ) Emergence of hypervirulent strain in Origin of Name NAP1/BI/027 - North American Pulsed Field Type 1 - Restriction enzyme analysis type BI - PCR ribotype 027 Increased production of toxins A and B Production of additional toxin binary toxin Increased resistance to fluoroquinolones Routine labs do not differentiate this epidemic strain

8 2010 SHEA and IDSA Clinical Practice Guidelines Infection Control for Patients with C. difficile Isolate patients with C. difficile Wear gloves and gowns when entering room Hand sanitizer does not kill C. difficile, and hand washing may not be sufficient In outbreak setting (or increased infection rate), wash hands with soap and water after leaving room Clean room surfaces with bleach or another EPAapproved, spore-killing disinfectant when patient leaves In outbreak setting (or increased infection rate), wash hands with soap and water after leaving room

9 2013

10 2013 APIC Implementation Guide Discontinuing Contact Precautions Contact Precautions may be discontinued when the patient no longer has diarrhea. Some experts recommend continuing Contact Precautions for 2 days after diarrhea stops (Because of continued environmental contamination and patient skin colonization*) If rates of CDI remain high, Contact Precautions may be continued until hospital discharge.17 *Notes: - Up to 70 percent of patients have skin contamination with C. difficile 6 days after resolution of diarrhea - 40 percent may have skin contamination up to 9 days after the resolution of diarrhea Source: APIC Implementation Guide. 2013

11 Clostridium difficile 2010 SHEA and IDSA Clinical Practice Guidelines Severity of Disease Recommended Therapy for 1 st Episode Mild-moderate WBC <15,000 AND Creatinine <1.5x baseline Severe WBC > 15,000 OR Creatinine > 1.5x baseline Severe, Complicated Hypotension OR Shock, Ileus, Megacolon Metronidazole: 500 mg PO TID x days Vancomycin: 125 mg PO QID x days Vancomycin: 500 mg PO QID +/- Metronidazole: 500 mg IV q8h If Ileus Present, add Vancomycin: 500 mg in 100 ml normal saline per rectum QID (retention enema) Source: Cohen SH, et al. Infect Control Hosp Epi. 2010;31:

12 HIV Postexposure Prophylaxis

13 2013 Source: Kuhar DT, et al. Infect Control Hosp Epidemiol. 2013;34:

14 Seroconversion (%) Estimated Risk of Seroconversion with Percutaneous Injury ???? HIV Hepatitis C HBsAg+ HBeAg- HBsAg+ HBeAg+ Source: CDC and Prevention. MMWR Morb Mortal Weekly Rep. 2001;50(RR-11):1-42.

15 Seroconversion (%) Estimated Risk of Seroconversion with Percutaneous Injury HIV Hepatitis C HBsAg+ HBeAg- HBsAg+ HBeAg+ Source: CDC and Prevention. MMWR Morb Mortal Weekly Rep. 2001;50(RR-11):1-42.

16 Estimated Risk of HIV Transmission with Different Exposures Risk of HIV Transmission in Health Care Workers Type of Exposure to Blood Risk of HIV Transmission Percutaneous Exposure? Mucous Membrane Exposure? Nonintact Skin Exposure % Source: CDC and Prevention. MMWR Morb Mortal Weekly Rep. 2001;50(RR-11):1-42.

17 Estimated Risk of HIV Transmission with Different Exposures Risk of HIV Transmission in Health Care Workers Type of Exposure to Blood Risk of HIV Transmission Percutaneous Exposure 0.3% Mucous Membrane Exposure 0.09% Nonintact Skin Exposure < 0.09% Source: CDC and Prevention. MMWR Morb Mortal Weekly Rep. 2001;50(RR-11):1-42.

18 Case History HIV Exposure in a Health Care Worker A 41-year-old nurse has a needlestick injury on his left thumb. The site bled for about 2 minutes after the injury. The source patient has documented HIV infection, has never taken antiretroviral medications, and most lab studies showed HIV RNA level of 2,350 copies/ml and CD4 count of 658 cells/mm 3. Based on USPHS 2013 Guidelines, what is recommended? A. Zidovudine-lamivudine (Combivir) B. Tenofovir-emtricitabine (Truvada) C. Tenofovir-emtricitabine (Truvada) + Raltegravir (Isentress) D. Tenofovir-emtricitabine (Truvada) + Darunavir (Prezista) + ritonavir (Norvir)

19 2013 USPHS Occupational PEP Guidelines Number of Antiretroviral Medications to Use As less toxic and better-tolerated medications for the treatment of HIV infection are now available, minimizing the risk of PEP noncompletion, and the optimal number of medications needed for HIV PEP remains unknown, the PHS working group recommends prescribing 3 (or more) tolerable drugs as PEP for all occupational exposures to HIV. Source: Kuhar DT, et al. Infect Control Hosp Epidemiol. 2013;34:

20 2013 USPHS Occupational PEP Guidelines Recommendations for Antiretroviral Regimens Recommended Antiretroviral Regimens for Occupational PEP (28-Day Duration) Preferred Regimen INSTI NNRTI Pill Burden Raltegravir (Isentress) 400 mg twice daily Tenofovir-Emtricitabine (Truvada) 1 pill daily Source: Kuhar DT, et al. Infect Control Hosp Epidemiol. 2013;34:

21 2013 USPHS Occupational PEP Guidelines Recommendations for Antiretroviral Regimens Alternative Antiretroviral Regimens for Occupational PEP (28-Day Duration) INSTI, PI, or NNRTI NNRTI Alternative Regimens: Combine from both columns (listed in order of preference) Raltegravir (Isentress) Darunavir (Prezista) + Ritonavir (Norvir) Etravirine (Intelence) Rilpivirine (Edurant) Atazanavir (Reyataz) + Ritonavir (Norvir) Lopinavir-Ritonavir (Kaletra) Tenofovir-Emtricitabine (Truvada) Tenofovir (Viread) + Emtricitabine (Emtriva) Tenofovir (Viread) + Lamivudine (Epivir) Zidovudine-Lamivudine (Combivir) Zidovudine (Retrovir) + Lamivudine (Epivir) Zidovudine (Retrovir) + Emtricitabine (Emtriva) Alternative Regimen: Fixed-Drug Combination Elvitegravir-Cobicistat-Tenofovir-Emtricitabine (Stribild) Source: Kuhar DT, et al. Infect Control Hosp Epidemiol. 2013;34:

22 2013 USPHS Occupational PEP Guidelines Major Changes Eliminates evaluation of level of risk to stratify PEP regimen All PEP regimens should contain 3 or more medications New recommended and alternative PEP regimens Follow up may conclude at 4 months if 4 th generation HIV testing used Source: Kuhar DT, et al. Infect Control Hosp Epidemiol. 2013;34:

23 2013 USPHS Occupational PEP Guidelines Situations for Which Expert Consultation Advised Delayed exposure report (eg. longer than 72 hours) Unknown source (eg. needle in sharps disposal) Known or suspected pregnancy in exposed person Exposed person breast-feeding Known or suspected ARV drug resistance in source patient Serious medical illness in exposed persons Toxicity occurring in exposed person taking PEP regimen Source: Kuhar DT, et al. Infect Control Hosp Epidemiol. 2013;34:

24 Post-Exposure Prophylaxis Line (PEPline)

25 Clostridium difficile : Fidaxomicin vs Vancomycin Study Design Study Design Protocol - N = 629 enrolled (548 evaluated) - Double-blind, prospective, randomized trial - Phase 3 trial - Conducted from Age: 16 years and older - Acute symptoms of C. diff and +stool toxin - Randomized to fidaxomicin or vancomycin Treatment Arms Fidaxomicin 200 mg PO BID X 10 days Vancomycin 125 mg PO QID x 10 days From: Louie TJ, et al. N Engl J Med. 2011;364:

26 Patients % Clostridium difficile: Fidaxomicin vs Vancomycin Results Fidaxomicin 80 Vancomycin Clinical Cure* P < Recurrence^ Clinical Cure = resolution of symptoms and no need for further therapy Recurrence = diarrhea and positive stool test within 4 weeks after treatment From: Louie TJ, et al. N Engl J Med. 2011;364:

27 Clostridium difficile Treatment of Recurrent Infection First Recurrence - Same as initial episode Second Recurrence - Do not use metronidazole - Vancomycin: tapered and/or pulse regimen - Fidaxomycin: 200 mg bid x 14d Greater than 2 nd Recurrence - Repeated courses of Vancomycin - Toxin binders, including monoclonal antibodies - Fidaxomycin: 200 mg bid x14d or Rifaxamin: 400 mg bid x14d - Saccharomyces boulardii and other probiotics - Fecal transplantation - Immunization with C. difficile vaccine

28 Methicillin-Resistant Staphylococcus aureus (MRSA)

29 MRSA Community-Acquired Hospital-Acquired USA-300 USA-100

30 Free Access Via Web Source: Liu C, et al. Clin Infect Dis. 2011:52:1-38.

31 Case History: Skin & Soft Tissue A 28-year-old man presents with an abscess on his hand and fever (T = 38.6 C). He has diabetes, but no other medical problems. The patient says this is a spider bite, but he has a history of 2 prior MRSA infections.

32 2010 IDSA Practice Guidelines Therapy for CA-MRSA Skin & Soft Tissue Infection Empiric Therapy for Out-Patient Management - TMP-SMX: 1-2 DS tabs PO BID - Clindamycin: mg PO TID - Doxycycline: 100 mg PO BID - Minocycline: 200 mg x1, then 100 mg PO BID - Linezolid: 600 mg PO BID If Also Covering for Group A Streptococcus - TMP-SMX + Amoxicillin: 500 mg PO TID - Clindamycin - Doxycycline/Minocycline + Amoxicillin: 500 mg PO TID - Linezolid Source: Liu C, et al. Clin Infect Dis. 2011:52:1-38.

33 Staphylococcus aureus colonization Persistent Carrier Intermittent Carrier Non Carrier 60% 20% 20% MRSA Persistent Carrier < 5% Source: Liu C, et al. Clin Infect Dis. 2011:52:1-38.

34 2010 IDSA Practice Guidelines MRSA Decolonization Nasal Decolonization - Mupirocin: bid x 5-10 days Topical Body Decolonization - Chlorhexidine: once daily x 5-14 days - Dilute bleach bath*: 2x/week x 3 months Oral Antimicrobials (if topical therapy fails) - Consider active agent + Rifampin *Dilute bleach bath = 1 teaspoon per gallon of water [or ¼ cup per ¼ tub or 13 gallons of water] for 15 minutes twice weekly for 3 months Source: Liu C, et al. Clin Infect Dis. 2011:52:1-38.

35 Ceftaroline Class: Cephalosporin ( 5 th Generation ) Mechanism: Inhibits cell wall synthesis (binds to PBP, including PBP2a) Dose: 600 mg IV q12 hours Activity: - Broad gram-positive activity: MSSA, MRSA, VISA, DRSP - Gram-negative: Enterobacteriaceae - Not active against Pseudomonas sp. or Proteus sp., or E. faecium Clinical: - Skin and soft tissue infections (CANVAS 1 & 2 Studies) - Community-acquired pneumonia (FOCUS 1 & 2 Studies) Adverse Effects: seroconversion to positive direct Coombs test Source: Saravolatz LD, et al. Clin Infect Dis. 2011;52:

36 Ceftaroline and MRSA: Mechanism of Action Altered Penicillin Binding Protein PBP 2a Ceftaroline PBP 2a DNA

37 Question and Answer Session

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