FEVER IN THE ICU Infectious Diseases in Clinical Practice February - PDF document

2/17/16 ¡ FEVER IN THE ICU Infectious Diseases in Clinical Practice February 2016 Jennifer Babik, MD, PhD Division of Infectious Diseases University of California, San Francisco Disclosures § None 1 ¡

2/17/16 ¡ Learning Objectives 1. To develop a framework for the differential diagnosis of fever in a patient in the ICU 2. To know the common clinical presentation, diagnosis, and management of common infections in the ICU 3. To recognize the common non-infectious etiologies for fever in the ICU Outline Infections in the ICU Non-infectious Etiologies for Fever in the ICU • Line Infections • Drug fever • “Double-covering GNRs” • VTE • CA-UTI • VAP and nosocomial • Central fever sinusitis • Acalculous cholecystitis • Candidemia 2 ¡

2/17/16 ¡ Definition of Fever § Definition of fever is arbitrary • ≥ 38.3°C (101°F) commonly used (IDSA/ACCCM guidelines) • Use a lower threshold in immunocompromised patients • T < 36.0°C should also prompt an investigation for infection § Note that patients on CRRT or ECMO may not mount a fever even when infected O’Grady et al, Crit Care Med 2008, 35:1330. Fever in the ICU: Epidemiology § Fever occurs in 25-70% of patients § Infectious vs non-infectious? • 35-55% are infectious • 45-65% are non-infectious! § Etiologies depended on type of ICU (MICU vs SICU vs NICU) • Most common infections: PNA, bloodstream, abdominal infections • Most common non-infectious etiologies: post-op fever, central fever Niven et al, J Intensive Care Med 2012, 27:290. 3 ¡

2/17/16 ¡ Treatment of Fever with Acetaminophen § Is fever good? (it may The new engl and jour nal o f medicine enhance immune cell Original Article function and inhibit Acetaminophen for Fever in Critically Ill Patients with Suspected Infection organism growth) § RCT of 700 ICU patients given acetaminophen or placebo to treat fever in known or § Is fever bad? (it may put suspected infection additional physiologic § No difference in # ICU-free days stress on the body) or on mortality Young et al, NEJM 2015, 373:2215. Framework for Building the DDx Is this a complication of the underlying reason for admission? 1. • Untreated, relapsed, or metastatic focus of infection • Post-surgical infection (surgical site infection, intra-abdominal abscess) Is this a separate nosocomial process? 2. • Hospital-acquired PNA (VAP, aspiration) • CA-UTI • Central Line-Associated Blood Stream Infection (CLABSI) • Clostridium difficile Is this non-infectious? 3. • Drug fever • Central fever 4 ¡

2/17/16 ¡ DDx: Head-to-Toe Approach • Nosocomial meningitis • Osteomyelitis CNS (post-NSG) MSK • Septic arthritis • Gout • Nosocomial Sinusitis HEENT • Cellulitis at line sites • Hospital-acquired URI Skin • Infected decub ulcer • Surgical site infection • Hospital-acquired PNA Pulmonary • Empyema • CLABSI Bloodstream • Candidemia • Endocarditis Cardiac • Pericarditis • Drug Fever • Central fever • DVT/PE • C. Difficile Other non- • Malignancy • CA-UTI infectious • Rheumatologic • Post-op abd abscess etiologies • Post-op fever GI/GU • Peritonitis • Transfusion reaction • Acalculous cholecystitis • Transplant rejection • Pancreatitis • Adrenal insufficiency Initial Evaluation § History: § Labs: • Any change in secretions or • CBC with diff (look for eos) respiratory status? • LFTs (drug reaction, acalculous • Any diarrhea? cholecystitis) § Micro: § Exam to include: • Blood cultures (DTTP) • Careful neuro exam • UA +/- Ucx • Sinus exam • Respiratory cultures? • Back and joint exam • Cdiff? • Skin exam: • Line sites • Decubitus ulcers § Imaging: • Rashes • CXR • Remove bandages • Chest or abdominal imaging? 5 ¡

2/17/16 ¡ Approach to Management § Do you need to treat empirically or can you wait for cultures/ diagnostics? § Is there a source control procedure needed? § For empiric therapy: • How sick is the patient? • Where do you think the patient is infected? • Prior positive cultures? • Prior antibiotics? • Is the patient at risk for MDR organisms? Case #1 A 55 year old man with ESRD and poor vascular access is admitted to the ICU with a STEMI. § He is slowly improving but then spikes a fever to 39˚C. § He is found to be bacteremic with Klebsiella pneumoniae from both his HD line and peripheral blood cultures. § He improves with empiric antibiotic and wants to go home. 6 ¡

2/17/16 ¡ Do You Need to Change the Line? Yes 1. No 2. I need more information 3. CLABSI: Diagnosis § Clinical findings unreliable: • Inflammation at the exit site is very insensitive (<3%) § Catheter tip culture: • Positive peripheral bcx and > 15 CFU/plate of same organism from catheter tip • 79% sensitive, 92% specific • But >80% of catheters withdrawn b/c of clinical suspicion of CLABSI are removed unnecessarily Mermel et al, Clin Infect Dis 2009, 49:1. Safdar and Maki, Crit Care Med 2002, 30:2632. 7 ¡

2/17/16 ¡ CLABSI: Differential Time to Positivity § Allows for diagnosis without removing the line § Draw culture from line + peripheral blood at the same time § CLABSI = blood culture drawn from central line turns positive at least 2 hrs before the peripheral culture § Test characteristics • 85-95% sensitive • 83-90% specific Liñares, Clin Infect Dis 2007, 44:827. Bouza et al, Clin Infect Dis 2007, 44:820. Bouza et al, Clin Microbiol Infect 2013, 19: E129. Safdar et al, Ann Intern Med 2005, 142:251. DTTP: Possible Scenarios Line (+) and peripheral (+) Line (+) and peripheral ( − ) Possibili1es ¡ DTTP ≥ 2 hrs DTTP < 2 hrs • Line ¡coloniza1on ¡ ¡ • Contaminant ¡ • Bacteremia ¡from ¡other ¡ source ¡with ¡1/2 ¡posi1ve ¡ Look for CLABSI cultures ¡ another source 8 ¡

2/17/16 ¡ Case #1 Continued § You find out that the blood culture drawn from the HD line turned positive 4 hours before the peripheral blood culture. § You are convinced the line is the source of the Klebsiella. Do You Need to Change the Line? Yes, always for Klebsiella irrespective of line type 1. No, you can consider line retention because it is an HD 2. catheter 9 ¡

2/17/16 ¡ When to Remove the Line Complicated Infections Certain Organisms § Severe sepsis § Virulent organisms • Staphylococcus aureus § Persistent bacteremia (>72h of appropriate ABx) • Pseudomonas • Candida § Septic thrombophlebitis § Exit site or tunnel infection § Evidence of metastatic infection: endocarditis, osteomyelitis Mermel et al, Clin Infect Dis 2009, 49:1 Line Management for Other Organisms Organism PICC/Short-term Tunneled Cath/ HD Catheter CVC Port Coag-negative Remove or retain Remove or retain Retain or guidewire staphylococci exchange Enterococcus Remove Remove or retain Remove, retain or guidewire exchange Other GNRs (not Remove Remove or retain Remove, retain or Pseudomonas ) guidewire exchange Less aggressive with line removal Mermel et al, Clin Infect Dis 2009, 49:1 10 ¡

2/17/16 ¡ Line Salvage § General principles • Treat with antibiotic lock therapy PLUS systemic ABx for 7-14 d • Get surveillance blood cultures 1 week after stopping ABx § Antibiotic Lock Therapy • Fill the catheter with supra-therapeutic ABx concentrations to kill intra- luminal bacteria and penetrate biofilms • Success rate for line salvage is ~75% (depends on organism) • Cannot use if signs of exit site/tunnel infection (extra-luminal infection) § Give systemic ABx through the line? • Good in theory but no data • It is recommended in IDSA guidelines if ABx lock is not an option Mermel et al, Clin Infect Dis 2009, 49:1 Line Management: Take-Home Points § Differential time to positivity (line positive ≥ 2 hours before peripheral) allows for diagnosis of CLABSI without line removal § All lines should be removed for: • Any complicated infection • Staph aureus, Pseudomonas, or Candida § Line management for other organisms depends on line type (lower barrier to remove line for short term catheter > long- term catheter > HD catheter) 11 ¡

2/17/16 ¡ Case #2 A 57 year old woman with breast cancer undergoing chemotherapy with several recent admissions for UTI treated with carbepenems or ciprofloxacin is admitted to the ICU with presumed pyelonephritis. § She is febrile to 39.6˚C, tachy to 120s, rapidly uptitrated to max doses on 3 pressors. § WBC is 0.8 (ANC<500), Cr 1.8, other labs normal. Renal US is normal. § Blood and urine cultures are drawn and she is started on vancomycin plus meropenem. What Would You Do With Her ABx? 1. No changes (this is a source control issue) 2. No changes (ABx have not had time to work yet) 3. Add an aminoglycoside 4. Add a fluoroquinolone 12 ¡

2/17/16 ¡ Case #2 Continued § Blood and urine cultures return positive with Pseudomonas susceptible to all agents except cipro/levo. § Pressor requirement is downtrending. § Should you continue “double-coverage” or change to beta- lactam monotherapy? What Would You Do With Her ABx Now? 1. Continue “double coverage” 2. Change to beta-lactam monotherapy 13 ¡