Clostridium difficile

Transcription

1 Management of Common Inpatient Infections: MRSA, C diff, VRE, and more Bradley A. Sharpe, M.D. Associate Professor Medicine Department of Medicine UCSF sharpeb@medicine.ucsf.edu Roadmap Background MRSA Clostridium difficile VRE More Specific Goals: Appreciate the morbidity and mortality associated with hospital-acquired infections (HAIs). Describe optimal therapy for MRSA infections. List key principles in the management of Clostridium difficile infection. Understand evidence for preventing HAIs. Caveats Will discuss hospital-acquired infections + community-acquired Cannot cover all in-depth Often complex patients (ID consult?) Highlight key principles, what you need to know 1

2 Roadmap Inpatient Infections Background MRSA Clostridium difficile VRE More Estimated 1.7 million HAIs per year (2002) -- Up to 10% of all hospitalized patients Responsible for 99,000 deaths/year Cost of $4.5 - $11 billion/year Klevens RM, et al. Pub Health Reports. 2007;122:160. Inpatient Infections 2

3 Roadmap Background MRSA Clostridium difficile VRE More MRSA Epidemiology Facultative gram-positive Colonizer in humans (mainly nares) -- 20% persistent, 30% intermittent Transmitted in the hospital (your hands) Ammerlaan HS, et al. CID. 2009;49:922. Solberg, CO. Scand J Infect Dis. 2000;32: History of Staphylococcus aureus: HA-MRSA, CA-MRSA, VISA, VRSA Introduction of methicillin 1 st MRSA isolate identified VISA VISA JapanU.S Report of MRSA infxn in children w/o classic risk factors 99 MMWR report of 4 deaths due to MRSA in previously healthy children VRSA U.S. 02 Outbreaks of CA- MRSA reported in multiple diverse populations 11 th case VRSA CA-MRSA predominant cause of SSTI New Patients/1000 Patient Days MRSA Isolated from Adult & Pediatric In-Patients Moffitt-Long/ Mt.Zion Year COMM/1000 PT DAYS HOSP ONSET/1000 PT DAYS TOTAL/1000 PT DAYS Linear Comm = specimen collected < 3 days after admission Hosp Onset = specimen collected > 3 days after admission 3

4 MRSA Infections Skin and soft-tissue infections (SSTIs) Pneumonia (CAP, HCAP, HAP, VAP) Bacteremia/endocarditis Bone and joint infections Other (epidural abscess, etc.) 1. A 34 man with no PMH presents with 3 days of forearm redness & pain; started after moving furniture. He is afebrile and looks well. Physical Exam 1. A 34 man with no PMH presents with 3 days of forearm redness & pain; started after moving furniture. He is afebrile, looks well. Which antibiotic would you choose? a. Trimethoprim/sulfamethoxazole PO 47% b. Clindamycin PO c. Cephalexin PO d. Amoxicillin PO + TMP/SMX PO e. Vancomycin PO f. Steroids. I treat all rashes with steroids. Trimethoprim/s... Clindamycin PO 4% Cephalexin PO 47% Amoxicillin PO... 2% Vancomycin PO 0% 0% Steroids. I t... 4

5 Skin & Soft-tissue tissue Infections Most common Staphyloccocus Aureus and streptococcal species (GAS) Depends on purulent vs. non-purulent infection Purulent SSTIs Furuncle Carbuncle Abscess Cellulitis with purulence Microbiology of Purulent SSTI 4.5% 8.1% 9.0% 2.6% 17.0% 59.0% MRSA B-hemolytic strep other MSSA non-b hemolytic strep unknown Moran NEJM

6 CA-MRSA Susceptibilities Antimicrobials TMP/SMX 100% Rifampin 100% Clindamycin 95% Tetracycline 92% Fluoroquinolones 60% Erythromycin 6% Moran GJ. NEJM % susceptible Purulent SSTIs - Treatment Outpatient (PO) Clindamycin Trimethoprim-sulfamethoxazole Tetracycline (doxycycline) Inpatient (IV) Vancomycin Non-Purulent SSTIs Erisypelas -- Raised above skin -- Clear borders Cellulitis -- Poorly defined borders CAP: A Practical Approach 6

7 Non-Purulent SSTIs Treat MRSA in non-purulent SSTI Probably β-hemolytic streptoccal (group A strep) in most cases -- Likely > 70% Unclear how often CA-MRSA in nonpurulent SSTIs -- Role of CA-MRSA is unknown Risk factors: -- Hemodialysis, IVDU, SNF, recent abx Known prior MRSA (Possibly) MRSA rates > 30% Systemic illness -- Fever, appearing ill, etc. Liu C, et al. CID. 2011;52:285. Jeng A, et al. Medicine. 2010;89:217. Stevens DL, et al. CID. 2005;41:1373. Non-Purulent SSTIs - Treatment Skin & soft-tissue, tissue, MRSA NO MRSA Risk* Outpatient (PO) Dicloxacillin Cephalexin Inpatient (IV) Cephazolin (?) MRSA Risk Outpatient (PO) Clindamycin Amoxicillin/TMP-SMX Linezolid Inpatient (IV) Vancomycin Likely cause of purulent SSTIs. May or may not be involved with nonpurulent SSTIs. If the patient is sick, treat for MRSA. Duration: 5-10 days. * If worse after 2 nd day of treatment, consider change Liu C, et al. CID. 2011;52:285. 7

8 1. A 34 man with no PMH presents with 3 days of forearm redness & pain; started after moving furniture. He is afebrile, looks well. Which antibiotic would you choose? Non-Purulent SSTIs - Treatment NO MRSA Risk* MRSA Risk a. Trimethoprim/sulfamethoxazole PO b. Clindamycin PO c. Cephalexin PO d. Amoxicillin PO + TMP/SMX PO e. Vancomycin PO f. Steroids. I treat all rashes with steroids. Outpatient (PO) Dicloxacillin Cephalexin Inpatient (IV) Cephazolin (?) Outpatient (PO) Clindamycin Amoxicillin/TMP-SMX Linezolid Inpatient (IV) Vancomycin * If worse after 2 nd day of treatment, consider change 1. A 34 man with no PMH presents with 3 days of forearm redness & pain; started after moving furniture. He is afebrile, looks well. Which antibiotic would you choose? a. Trimethoprim/sulfamethoxazole PO b. Clindamycin PO c. Cephalexin PO d. Amoxicillin PO + TMP/SMX PO e. Vancomycin PO f. Steroids. I treat all rashes with steroids. MRSA Infections Skin and soft-tissue infections (SSTIs) Pneumonia (CAP, HCAP, HAP, VAP) Bacteremia/endocarditis Bone and joint infections Other (epidural abscess, etc.) 8

9 MRSA Pneumonia Empiric Rx for MRSA for severe CAP (ICU admission, etc.) pending sputum and blood cx (AIII). Discontinue Rx if cultures do not grow MRSA Vancomycin or linezolid (AII). Superiority of either antibiotic unclear Daptomycin is inactivated by surfactant MRSA Infections Skin and soft-tissue infections (SSTIs) Pneumonia (CAP, HCAP, HAP, VAP) Bacteremia/endocarditis Bone and joint infections Other (epidural abscess, etc.) Francis JL CID 2005; Gonzalez BE Clin Infect Dis 2005; Hageman JC EID 2006; MMWR 2007; Mandell L CID 2007; Finelli L Pediatrics 2008; Rubinstein E CID 2001; Wunderink RG Clin Therap 2003; Wunderink RG Chest 2003 Jung Crit Care Med All patients with Staphylococcus aureus bacteremia should undergo echocardiography. 51% 43% 2. All patients with Staphylococcus aureus bacteremia should undergo echocardiography. a. True b. False c. It depends. d. No way. Do you think the cardiologists need to make more money? True False 6% It depends. 0% No way. Do you... a. True b. False c. It depends. d. No way. Do you think the cardiologists need to make more money? 9

10 MRSA Bacteremia and Endocarditis MRSA Bacteremia and Endocarditis All patients need echocardiography TEE preferred; can start with TTE For uncomplicated bacteremia, treat with 2 weeks of IV antibiotics No endocarditis, repeat cx negative, better in 3 days, no implanted prostheses For complicated bacteremia, treat with 4-6 weeks of IV antibiotics Vancomycin or daptomycin (AII) Addition of gentamicin (AII) or rifampin (AI) to vancomycin is not recommended for bacteremia or native-valve endocarditis No clear evidence of benefit for either drug 1 Increased risk of nephrotoxicity 2 with gentamicin Increased risk of drug interactions and development of rifampin resistance 3 Liu C, et al. CID. 2011;52: Levine D Annals of Intern Med 1991; Riedel DJ AAC 2008; 2 Rybak MJ AAC 1990; Goetz, MJ JAC 1993; Rybak MJ AAC 1999; Cosgrove SE CID Riedel DJ AAC 2008 ID Consult & Staph bacteremia?? Infection Control Complex disease, high mortality Infectious diseases consultation associated with improved outcomes -- Improved adherence to standards of care -- Decreased mortality by 40-60% Lahey T, et al. Medicine. 2009;88:263. Rieg S, et al. J Infect. 2009;59:232. Jenkins TC, et al. CID. 2008;46:1000. Honda H, et al. Am J Med. 2010;123:

11 MRSA Control: What s the Data? MRSA screening (active surveillance testing) -- Observational study over 3 consecutive time periods MRSA infections 1 -- Cluster randomized trial of surgical patients no benefit 2 Contact isolation -- Systematic review -- MRSA but many confounding interventions 3 -- Prospective study no change MRSA transmission 4 -- Potential adverse consequences: pressure ulcers, falls, depression 5 1 Robicsek Ann Intern Med 2008; 2 Harbarth JAMA 2008; 3 Cooper BMJ 2004; 4 Cepeda Lancet 2005; 5 Stelfox JAMA 2003; MRSA Control: What s the Data? Hand hygiene -- Alcohol hand rub HA-MRSA (20%) and VRE (40%), not C. diff 4 -- Hand hygiene compliance by 20% -- MRSA transmission by 50% 5 -- MRSA outbreaks: hand hygiene combined with other interventions works 6,7 4 Gordin ICHE 2005; 5 Pittet Lancet 2000; 6 Webster J Paediatr Child Health 1994; 7 Zafar Am J Inf Control Hand hygiene compliance and HA-MRSA rates at Massachusetts General Hospital HH and MRSA Rates Roadmap 120% 100% 80% 60% 40% 20% Before contact rates After contact rates MRSA Rate % % Background MRSA Clostridium difficile VRE More 0% 0.00 Quarter 3 Quarter 4 Quarter 1 Quarter 2 Quarter 3 Quarter 4 Quarter 1 Quarter 2 Quarter 3 Quarter 4 Quarter 1 Quarter 2 Quarter 3 Quarter 4 Quarter 1 Quarter 2 Quarter 3 Quarter 4 Quarter 1 Quarter 2 Quarter 3 Quarter 4 Quarter 1 Quarter 2 Quarter 3 Quarter 4 Quarter 1 Quarter 2 Quarter 3 Quarter

12 C. Diff Microbiology C. Diff Epidemiology First isolated in 1935 (stool of a healthy infant) Named for difficulty in culture and isolation Association with disease recognized in 1978 Now leading cause of hospital-acquired diarrhea Since 2001, incidence AND severity & mortality (Especially 65 year olds) Multiple outbreaks in US between Due to a virulent BI/NAP1/027 strain: -- toxin A and B production -- Production of a binary toxin -- Deletion of tcdc gene (negative regulator of toxin prod) Heinlen L, et al. Am J Med Sci. 2010;340:247. Heinlen L, et al. Am J Med Sci. 2010;340: There are 80 people at the conference. What percentage of all of you are colonized with C diff (assume none have been hospitalized recently)? 3. There are 80 people at the conference. What percentage of all of you are colonized with C diff (assume none have been hospitalized recently)? a. 90% 25% b. 50% 20% 18% c. 10% d. 2% e. 0% f. I can t believe I just licked my fingers 90% 50% 10% 25% 2% 6% 6% 0% I can t believ... a. 90% b. 50% c. 10% d. 2% e. 0% f. I can t believe I just licked my fingers 12

13 C. Diff Pathogenesis Only 2-3% of healthy adults are colonized with C diff. Up to 40% of hospitalized patients are colonized (not all pathogenic) Transmitted by all of you Heinlen L, et al. Am J Med Sci. 2010;340:247. C. diff Risk Factors C. diff Risk Factors 1) Antibiotic exposure (last 2-3 months) Highest Risk Clindamycin Cephalosporins Penicillins Fluoroquinolones Lower Risk Aminoglycosides Vancomycin Metronidazole Tetracyclines 1) Antibiotic exposure (last 2-3 months) 2) Hospitalization 3) Advanced age ( 65 yrs. old) 4) Proton Pump Inhibitors Heinlen L, et al. Am J Med Sci. 2010;340:247. Heinlen L, et al. Am J Med Sci. 2010;340:

14 C. Diff Diagnosis C. Diff Diagnosis If the stool is not loose, the test is no use. Perform testing only on diarrheal (unformed) stool (B-II) -- Only ~1% have ileus from severe colitis -- Usually 3 times/day Do not test asymptomatic patients; no role for test of cure. (B-III) Heinlen L, et al. Am J Med Sci. 2010;340:247. Heinlen L, et al. Am J Med Sci. 2010;340:247. C. Diff Diagnosis C. Diff Treatment Many different tests available Most are ELISA for toxin or for cell membrane proteins Find out your local testing most have very high sensitivity Stop inciting antibiotic if possible! (A-II) Treat empirically if suspect severe or complicated C. difficile (C-III) Consider colectomy for severely ill patients (B-II) consult surgery early! Heinlen L, et al. Am J Med Sci. 2010;340:247. Heinlen L, et al. Am J Med Sci. 2010;340:

15 4. A 65 yo man hospitalized 5 days prior for CAP now has fever, abdominal pain, and diarrhea (yes, loose). He appears ill and has a wbc of 22,000 and new acute renal failure (creatinine 2.2 mg/dl). A C diff test comes back positive. What is the optimal initial treatment? 4. A 65 yo man hospitalized 5 days prior for CAP now has fever, abdominal pain, and diarrhea (yes, loose). He appears ill and has a wbc of 22,000 and new acute renal failure (creatinine 2.2 mg/dl). A C diff test comes back positive. What is the optimal initial treatment? a. Clindamycin PO b. Vancomycin PO c. Metronidazole PO d. Vancomycin IV e. Stool transplant. 0% 31% 53% 12% 4% a. Clindamycin PO b. Vancomycin PO c. Metronidazole PO d. Vancomycin IV e. Stool transplant. Clindamycin PO Vancomycin PO Metronidazole... Vancomycin IV Stool transpla... C. Diff Treatment Oral Vancomycin vs. Oral Metronidazole? Initial antibiotic depends on severity of disease. Vancomycin Metronidazole 100% 98% 97% 90% Severe disease best defined as: WBC > 15,000 cells/microl OR Creatinine > 1.5x pre-morbid level Cure Rates 80% 60% 40% 20% p= 0.36 p= % N=150 0% Mild Infection Severe Infection Heinlen L, et al. Am J Med Sci. 2010;340:247. Zar, et al. CID

16 C. difficile Treatment: Initial Episode Mild/ moderate disease Severe Disease Severe Disease, Complicated WBC 15K, Cr < 1.5x premorbid level WBC>15K, Cr > 1.5x premorbid level Hypotension or shock, ileus, megacolon Metronidazole 500 mg PO q8h x days Vancomycin 125 mg PO q 6h x days Vancomycin 500 mg PO q6h AND Metronidazole 500 mg IV q8h *If ileus, consider PR vanco A-I B-I C-III C. Diff Prevention Wash your hands! Must use soap and water to kill spores (EtOH rub won t do it). Gown and gloves with suspected or documented C diff. Heinlen L, et al. Am J Med Sci. 2010;340:247. Roadmap Background MRSA Clostridium difficile VRE More 16

17 Enterococcus Microbiology Enterococci are gram positive cocci, identified in 1980s Two main enterococcal species E. faecalis: 85-90% of isolates E. faecium: 5-10% of isolates Normal colonizer of human GI tract Enterococcus Epidemiology Enterococcus causes infections in the hospital Second or third most common nosocomial infxn Generally fecal-oral transmission colonization infection Can survive in the hospital Risk factors for enterococcal infection: Long hospital or ICU admission Bone marrow or other transplant Urinary or vascular catheter Noskin GA, et al. Inf Cont Hosp Epid. 1995;16:577. What about VRE? What about VRE? Main risk factor is antibiotics (vanco, others) Rates of VRE have increased substantially Noskin GA, et al. Inf Cont Hosp Epid. 1995;16:577. Hidron HI, et al. Inf Cont Hosp Epid. 2008;29:

18 What about VRE? Common VRE Infections Main risk factor is antibiotics (vanco, others) Rates of VRE have increased substantially VRE associated with worse outcomes compared to vancomycin sensitive enterococcus Mortality odds ratio = 2.5 (95% CI, ) Urinary tract infection Bacteremia Intra-abdominal/pelvic infections Diazgranados CA, et al. CID. 2005;41: That same 65 yo man with C diff required ICU admission and remains intubated with respiratory failure. He has had an indwelling foley for 4 weeks. A U/A and culture are randomly sent (no fever or other signs or symptoms of infection). The U/A has wbc/hpf and the culture grows < 100,000 CFUs of enterococcus. What should you do? a. Start vancomycin IV b. Start linezolid PFT c. Start amoxicillin IV. d. Replace the foley catheter. e. Nothing. f. Talk to the family about goals of care. Start vancomyc... 3% Start linezoli... 17% 14% 14% Start amoxicil... 3% Replace the fo... 49% Nothing. Talk to the fa That same 65 yo man with C diff required ICU admission and remains intubated with respiratory failure. He has had an indwelling foley for 4 weeks. A U/A and culture are randomly sent (no fever or other signs or symptoms of infection). The U/A has wbc/hpf and the culture grows < 100,000 CFUs of enterococcus. What should you do? a. Start vancomycin IV b. Start linezolid PFT c. Start amoxicillin IV. d. Replace the foley catheter. e. Nothing. f. Talk to the family about goals of care. 18

19 VRE Urinary Tract Infection Urinary tract colonization w/ VRE common in ICU/hospital setting Can stay colonized for > 1 year Need to differentiate between: Colonization Asymptomatic bacteriuria True infection VRE Urinary Tract Colonization Most VRE in the urine is colonization In 100 pts, only 13% had true infection Others colonized or asymp. bacteriuria True infection more common in patients with cancer Byers KE, et al. Inf Cont Hosp Epid. 2002;23:207. Wong AH, et al. Am J Infect Cont. 2000;28:277. VRE Urinary Tract Infection True infection should include: 1) Symptoms (fever, confusion, malaise, flank pain, etc.) 2) Pyuria and/or leukocyte est/nitrate 3) 10 3 cfu/ml of enterococcus VRE UTI Treatment If true infection+ high-risk for VRE + ill, treat empirically for VRE Linezolid pending cultures Replace the foley catheter May help rid colonization Hooten TM, et al. CID. 2010;50:625. Heintz BH, et al. Pharmacotherapy. 2010;30:

20 Common VRE Infections Urinary tract infection Bacteremia Intra-abdominal/pelvic infections VRE Bacteremia Usually in patients with multiple morbidities From catheters, UTIs, GI tract Rarely associated with endocarditis Rarely associated with sepsis or severe illness Consider gram-negative polymicrobial infxn Wisplinghoff H, et al. CID. 2004;39:309. VRE Bacteremia Treat empirically for VRE in high-risk patients Await sensitivities Duration of treatment unclear Likely 1-2 weeks for bacteremia Probably 4-6 weeks for endocarditis Common VRE Infections Urinary tract infection Bacteremia Intra-abdominal/pelvic infections 20

21 VRE Abdominal/Pelvic Infection VRE Prevention Usually mixed aerobic/anaerobic infection Not the most virulent (vs. GNRs) If grow it in culture, should treat it Duration of treatment unclear parellel tx of other organisms Wash your hands! Data on contact isolation is mixed follow your local policy Roadmap Gram-negative HAIs Background MRSA Clostridium difficile VRE More MDR Pseudomonas aeruginosa MDR Acinetobacter baumanii ESBL producing E. coli and Klebsiella Carbapenem-resistant Enterobacteriaceae (CRE) 21

22 5. I always gel in and gel out (or wash) each time I see patients in the inpatient setting. 1. True 2. False 55% 45% True False Roadmap Specific Goals: Background MRSA Clostridium difficile VRE More Appreciate the morbidity and mortality associated with hospital-acquired infections (HAIs). Describe optimal therapy for MRSA infections. List key principles in the management of Clostridium difficile infection. Understand evidence for preventing HAIs. 22

23 MRSA Take-home Points Treat for MRSA with purulent SSTIs; consider in non-purulent SSTIs if risk factors or systemically ill Add vanco for patients with CAP admitted to the ICU Consider ID consultation in patients with S. aureus bacteremia C Diff. Take-home Points If the stool is not loose, the test is no use! Treat severe disease (wbc > 15,000, Cr > 1.5x) with oral vancomycin VRE Take-home Points VRE infections are generally in sick hospitalized patients. Management of Common Inpatient Infections: MRSA, C diff, VRE, and more Most patients with VRE in the urine are colonized or have asymp. bacteriuria For true infection, need symptoms + pyuria + positive culture. Bradley A. Sharpe, M.D. Associate Professor Medicine Department of Medicine UCSF sharpeb@medicine.ucsf.edu 23