Fever in the ICU Infectious Diseases in Clinical Practice February - PDF document

Fever in the ICU Infectious Diseases in Clinical Practice February 2020 Jennifer Babik, MD, PhD Associate Clinical Professor Division of Infectious Diseases, UCSF Disclosures  I have no disclosures. 1

Learning Objectives By the end of this talk, you will be able to: 1. Construct a framework for the differential diagnosis of fever in a patient in the ICU 2. Describe the common clinical presentation, diagnosis, and management of common infections in the ICU 3. Recognize the common non ‐ infectious etiologies for fever in the ICU Roadmap  Introduction/Framework  Case ‐ based approach to common infectious and non ‐ infectious etiologies for fever in the ICU  CLABSI  CA ‐ UTI  VAP  Non ‐ infectious etiologies  Short takes (nosocomial sinusitis, acalculous cholecystitis)  “Double covering” GNRs 2

Definition of Fever  Definition of fever is arbitrary  ≥ 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  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. Measurement of Fever  Central thermometers (bladder, rectal, esoph) ≈ pulmonary artery temperatures  Peripheral thermometers have:  Poor correlation with central temperatures (± 0.5 ‐ 2 ˚ C)  High specificity (~95%) but poor sensitivity for detecting fever  Oral or tympanic: 75% sensitive  Temporal 63% sensitive  Axillary 42% sensitive Niven et al, Ann Intern Med 2015, 163:768. 3

Does the Height of the Fever Help With Etiology?  Hyperpyrexia = Fever >41.1 ˚ C (or >106 ˚ F)  Classic teaching is that infections are a rare cause of hyperpyrexia  But the data shows that infections are a frequent cause of hyperpyrexia in adults (at least 50% solely due to infection)  Causes:  Most common: Staph, Strep, GNRs  TB, candida, malaria, viruses Sioson and Brown, South Med J 1993, 86:773. Simon,JAMA 1976; 236:240. Fever in the ICU: Epidemiology  Fever is common (25 ‐ 70% Etiology for Fever in the ICU of ICU patients)  Non ‐ infectious etiologies occur frequently Non ‐ infectious Infectious 45 ‐ 65% 35 ‐ 55%  Most common causes:  Infections: PNA, bloodstream, abdominal  Non ‐ infectious: post ‐ op, central fever, drug fever Niven et al, J Intensive Care Med 2012, 27:290. von Vught et al, JAMA 2016, 315:1469. 4

Framework for Building the DDx 1. Is this a complication of the underlying reason for admission?  Untreated, relapsed, or metastatic focus of infection  Post ‐ surgical infection (surgical site infection, abdominal abscess) 2. Is this a separate nosocomial process?  Hospital ‐ acquired PNA (HAP, VAP)  CA ‐ UTI “big 4”  Central Line ‐ Associated Blood Stream Infection (CLABSI)  Clostridium difficile 3. Is this non ‐ infectious?  Drug fever  Central fever  Post ‐ op fever Initial Evaluation  History:  Labs:  Any change in secretions or  CBC with diff (look for eos) respiratory status?  LFTs (drug reaction,  Any diarrhea? acalculous cholecystitis)  Micro:  Exam to include:  Blood cultures  Careful neuro exam  UA +/ ‐ Ucx  Sinus exam  Respiratory cultures?  Back and joint exam  Cdiff testing?  Skin exam:  Line sites  Decubitus ulcers  Imaging:  Rashes  CXR  Remove bandages  Chest or abdominal CT? 5

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 36 year old man with AML is in the ICU for leukopheresis and induction therapy and clinically 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? 6

Would You Change the Line? 1. Yes 2. No Central Line Infections Exit site infection Bacteremia without • Tunnel infection (>2cm) (<2cm from exit site) overlying skin changes • Port pocket infection • 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 7

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  But >80% of catheters removed unnecessarily Mermel et al, Clin Infect Dis 2009, 49:1. Safdar and Maki, Crit Care Med 2002, 30:2632. CLABSI: Differential Time to Positivity  Allows for diagnosis without removing the line  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  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. 8

DTTP: Possible Scenarios Line (+) and peripheral (+) Line (+) and peripheral (+) Line (+) and peripheral ( − ) Line (+) and peripheral ( − ) DTTP ≥ 2 hrs DTTP ≥ 2 hrs DTTP < 2 hrs DTTP < 2 hrs Possibilities Possibilities Line colonization Line colonization • • Contaminant Contaminant • • Bacteremia from other source Bacteremia from other source • • Look for Look for with 1/2 positive cultures with 1/2 positive cultures CLABSI CLABSI another source another source DTTP for Candida ?  Not as good  DTTP cut ‐ off of 2h is 85% sensitive, 82% specific  The special case of C. glabrata :  Most slow growing Candida with median TTP of 37h (other species <30h)  Using 2hr cut ‐ off DTTP: sensitivity 77%, specificity 50%  Best DTTP cut ‐ off = 6h  sensitivity 63%, specificity 75% Park et al, J Clin Microbiol 2014, 52:2566. 9

When to Remove the Line Complicated Infections Virulent Organisms 1. Severe sepsis 1. Staphylococcus aureus 2. Persistent bacteremia 2. Pseudomonas (>72h of appropriate ABx) 3. Candida 3. Septic thrombophlebitis 4. Exit site or tunnel infection 5. Metastatic infection: endocarditis, osteomyelitis Mermel et al, Clin Infect Dis 2009, 49:1 Line Management for Other Organisms Less aggressive with line removal Organism PICC/Short ‐ term CVC Tunneled Cath/Port HD Catheter Coag ‐ negative Remove or retain Remove or retain Remove, retain, or staphylococci guidewire exchange Enterococcus Remove Remove or retain Remove, retain or guidewire exchange 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 10

Line Salvage: General Principles  Which patients?  Not for complicated infections, exit site infections, or virulent organisms  Only studied in long ‐ term catheters  How to treat?  Give systemic ABx + antibiotic lock therapy for 7 ‐ 14 d  Get surveillance blood cultures (1 wk after Abx stop) Mermel et al, Clin Infect Dis 2009, 49:1 Antibiotic Lock Therapy  Goal is to get supra ‐ therapeutic ABx concentrations to penetrate biofilms  Logistics  Work with pharmacy and nursing  Mix with heparin, dwell times are variable but usually <48h  Common Abx:  Gram positives: linezolid, vancomycin, cefazolin  Gram negatives: ceftazidime, ciprofloxacin, gentamicin 11

Line Salvage with Antibiotic Lock Therapy Overall Success Rate (%) Abx Lock Efficacy by Organism (%) 100 90 90 80 80 >90% 70 70 80 ‐ 90% 80 ‐ 90% 60 60 60 ‐ 75% 50 50 40 40 30 30 ‐ 45% 40 ‐ 55% 30 20 20 10 10 0 0 Systemic Systemic Line CoNS GNRs S.aureus Abx Abx + Lock removal Mermel et al, CID 2009, 49:1 Aslam et al. JASN 2014;25:2927. Fernandez ‐ Hidalgo and Almirante, Expert Rev Anti ‐ Infect Ther 2014, 12:117. Ashby et al, Clin J Am Soc Nephrol 2009, 4:1601. Beathard, JASN 1999, 10:1045. What About Guidewire Exchange?  Goal is to eliminate biofilm entirely  How good is it?  Limited data, mostly HD catheters  At least equal to ABx lock (~70% cure), maybe better  Likely better than ABx lock for S. aureus  When to consider using?  If HD catheter removal is clearly indicated but not feasible (especially for S. aureus ) Robinson et al, Kidney Int 1998, 53:1792. Shaffer, Am J Kid Dis 1995, 25:593. Mokrzycki et al, Dial Transpl 2006, 21:1024. Aslam et al. JASN 2014;25:2927 12