2/20/19 Disclosures I have no disclosures. Fever in the ICU - PDF document

2/20/19 Disclosures § I have no disclosures. Fever in the ICU Infectious Diseases in Clinical Practice February 2019 Jennifer Babik, MD, PhD Associate Clinical Professor Division of Infectious Diseases, UCSF Learning Objectives Roadmap By the end of this talk, you will be able to: § Introduction/Framework 1. Construct a framework for the differential diagnosis of § Case-based approach to common infectious and fever in a patient in the ICU non-infectious etiologies for fever in the ICU § CLABSI 2. Describe the common clinical presentation, diagnosis, § CA-UTI and management of common infections in the ICU § VAP 3. Recognize the common non-infectious etiologies for § Non-infectious etiologies fever in the ICU § “Double covering” GNRs § Short takes (nosocomial sinusitis, acalculous cholecystitis) 1

2/20/19 Definition of Fever Measurement of Fever § Definition of fever is arbitrary § Central thermometers (bladder, rectal, esoph) ≈ pulmonary artery temperatures § ≥38.3°C (101°F) commonly used (IDSA/ACCCM) § Use a lower threshold in immunocompromised patients § T < 36.0°C should also prompt work-up for infection § Peripheral thermometers have: § Poor correlation with central temperatures (± 0.5-2˚C) § Note that patients on CRRT or ECMO may not mount § High specificity (~95%) but poor sensitivity for detecting fever a fever even when infected § Oral or tympanic: 75% sensitive § Temporal 63% sensitive § Axillary 42% sensitive O’Grady et al, Crit Care Med 2008, 35:1330. Niven et al, Ann Intern Med 2015, 163:768. Fever in the ICU: Epidemiology Framework for Building the DDx 1. Is this a complication of the underlying reason for admission? § Fever is common (25-70% § Untreated, relapsed, or metastatic focus of infection Etiology for Fever in the ICU of ICU patients) § Post-surgical infection (surgical site infection, abdominal abscess) § Non-infectious etiologies 2. Is this a separate nosocomial process? occur frequently § Hospital-acquired PNA (HAP, VAP) Non-infectious Infectious § CA-UTI “big 4” 45-65% 35-55% § Most common causes: § Central Line-Associated Blood Stream Infection (CLABSI) § Clostridium difficile § Infections: PNA, bloodstream, abdominal 3. Is this non-infectious? § Non-infectious: post-op, central fever, drug fever § Drug fever § Central fever § Post-op fever Niven et al, J Intensive Care Med 2012, 27:290. von Vught et al, JAMA 2016, 315:1469. 2

2/20/19 Initial Evaluation Approach to Management § History: § Labs: § Do you need to treat empirically or can you wait for cultures/diagnostics? § Any change in secretions or § CBC with diff (look for eos) respiratory status? § LFTs (drug reaction, § Any diarrhea? acalculous cholecystitis) § Is there a source control procedure needed? § Micro: § Exam to include: § Blood cultures § Careful neuro exam § For empiric therapy: § UA +/- Ucx § Sinus exam § How sick is the patient? § Respiratory cultures? § Back and joint exam § Where do you think the patient is infected? § Cdiff testing? § Skin exam: § Line sites § Prior positive cultures? § Imaging: § Decubitus ulcers § Prior antibiotics? § Rashes § CXR § Is the patient at risk for MDR organisms? § Remove bandages § Chest or abdominal CT? Case #1 Would You Change the Line? A 36 year old man with AML is in 1. Yes the ICU for leukopheresis and induction therapy and clinically 2. No improves. He then spikes a fever but remains stable. § He is bacteremic with Staph epidermidis from both his line and peripheral blood cultures § He improves with vancomycin. Can we leave the tunneled line in? 3

2/20/19 Central Line Infections Central-Line Associated BSI (CLABSI): Diagnosis § Clinical findings at exit site in <3% § Catheter tip culture: § (+) peripheral bcx and > 15 cfu/plate from catheter tip § 80% sensitive, 90% specific Exit site infection • Tunnel infection (>2cm) Bacteremia without (<2cm from exit site) • Port pocket infection overlying skin changes § But >80% of catheters removed unnecessarily • With or without BSI • With or without BSI • BSI by definition • If blood cultures neg, can • Remove the line, even • Line removal depends on try to salvage the line. if blood cultures neg. organism, clinical situation Mermel et al, Clin Infect Dis 2009, 49:1. Safdar and Maki, Crit Care Med 2002, 30:2632. CLABSI: Differential Time to Positivity DTTP for Candida ? à Not as good § Allows for diagnosis without removing the line § DTTP cut-off of 2h is 85% sensitive, 82% specific § Culture from line + peripheral blood at the same time § The special case of C. glabrata : § Most slow growing Candida with median TTP of 37h § CLABSI = blood culture drawn from central line turns (other species <30h) positive at least 2 hrs before the peripheral culture § Using 2hr cut-off DTTP: sensitivity 77%, specificity 50% § Best DTTP cut-off = 6h à sensitivity 63%, specificity 75% § Test characteristics § 85-95% sensitive § 85-90% 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. Park et al, J Clin Microbiol 2014, 52:2566. 4

2/20/19 When to Remove the Line Line Management for Other Organisms Complicated Infections Virulent Organisms Less aggressive with line removal 1. Severe sepsis 1. Staphylococcus aureus Organism PICC/Short-term CVC Tunneled Cath/Port HD Catheter 2. Persistent bacteremia 2. Pseudomonas Coag-negative Remove or retain Remove or retain Remove, retain, or (>72h of appropriate ABx) staphylococci guidewire exchange 3. Candida 3. Septic thrombophlebitis 4. Exit site or tunnel infection Enterococcus Remove Remove or retain Remove, retain or guidewire exchange 5. Metastatic infection: endocarditis, osteomyelitis Other GNRs (not Remove Remove or retain Remove, retain or Pseudomonas ) guidewire exchange Use clinical judgment based on: • Severity of infection • Access options (talk to renal or onc) • Risk of removal/replacement Mermel et al, Clin Infect Dis 2009, 49:1 Mermel et al, Clin Infect Dis 2009, 49:1 Line Salvage: General Principles Antibiotic Lock Therapy § Goal is to get supra-therapeutic ABx § Which patients? concentrations to penetrate biofilms § Not for complicated infections, exit site infections, or virulent organisms § Logistics § Only studied in long-term catheters § Work with pharmacy and nursing § Mix with heparin, dwell times are variable but usually <48h § How to treat? § Common Abx: § Give systemic ABx + antibiotic lock therapy for 7-14 d § Gram positives: linezolid, vancomycin, cefazolin § Get surveillance blood cultures (1 wk after Abx stop) § Gram negatives: ceftazidime, ciprofloxacin, gentamicin Mermel et al, Clin Infect Dis 2009, 49:1 5

2/20/19 Line Salvage with Antibiotic Lock Therapy What About Guidewire Exchange? Overall Success Rate (%) Abx Lock Efficacy by Organism (%) § Goal is to eliminate biofilm entirely 100 90 90 80 § How good is it? 80 >90% 70 § Limited data, mostly HD catheters 70 80-90% 80-90% 60 § At least equal to ABx lock (~70% cure), maybe better 60 60-75% 50 § Likely better than ABx lock for S. aureus 50 40 40 30-45% 30 40-55% 30 § When to consider using? 20 20 § If HD catheter removal is clearly indicated but not feasible 10 10 (especially for S. aureus ) 0 0 Systemic Systemic Line CoNS GNRs S.aureus Abx Abx + Lock removal Robinson et al, Kidney Int 1998, 53:1792. Shaffer, Am J Kid Dis 1995, 25:593. Mokrzycki et al, Dial Transpl Mermel et al, CID 2009, 49:1 Aslamet al. JASN 2014;25:2927. Fernandez-Hidalgo and Almirante, Expert Rev 2006, 21:1024. Aslamet al. JASN 2014;25:2927 Anti-Infect Ther 2014, 12:117. Ashby et al, Clin J Am Soc Nephrol 2009, 4:1601. Beathard, JASN 1999, 10:1045. Line Management: Take-Home Points Case #2 § Differential time to positivity (line positive ≥ 2 hours 55 y/o woman in the ICU after a before peripheral) allows for diagnosis of CLABSI without complicated spinal surgery. She line removal remains intubated, spikes a fever on POD#3 and is pan-cultured. § All lines should be removed for: § She has thick secretions and a § Any complicated infection new CXR infiltrate. § S. aureus, Pseudomonas, or Candida § mBAL is growing MRSA. § UA (catheter): 25-50 WBC, Ucx § Line management for other organisms depends on line type (lower barrier to remove line for short term positive for VRE. catheter > long-term catheter > HD catheter) § Use antibiotic lock when possible for line salvage 6

2/20/19 Do You Need to Treat the VRE? Asymptomatic Bacteriuria 1. Yes ASB = (+) urine culture AND no signs/symptoms of UTI 2. No 3. Not sure Asymptomatic Bacteriuria is COMMON! The Heart of the Problem § It’s Hard to Ignore a Positive Culture § Seen in up to: § 25% of elderly, diabetic, HD patients, short-term catheters § 50% of patients in long term care facilities § Proof of concept study: § ~100% of patients with long-term catheters § At Mount Sinai, 90% of their inpatient urine cultures were ASB, and 50% were treated with ABx § Of positive urine cultures obtained on the wards after § They stopped reporting these (+) urine cultures in the EMR hospital admission à ~90% are ASB § Results: § The % of ASB that was treated dropped by 80% § Do not treat EXCEPT in pregnant women, GU § No untreated UTIs and no sepsis procedures, neutropenia/renal transplant Nicolle et al, Clin Infect Dis 2005, 40:643. Leis et al, Clin Infect Dis 2014, 58:980 Leis et al, Clin Infect Dis 2014, 58:980. 7