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

2/18/15 ¡ FEVER IN THE ICU Infectious Diseases in Clinical Practice February 2015 Jennifer Babik, MD, PhD Division of Infectious Diseases University of California, San Francisco Disclosures • None 1 ¡

2/18/15 ¡ Outline 1. Approach to the DDx of fever in the ICU 2. Clinical presentation, diagnosis, and management of common ICU infections • Catheter-related bloodstream infection • Catheter-associated UTI • Ventilator-associated PNA • Clostridium difficile 3. Common non-infectious causes of fever Fever in the ICU: Epidemiology • Fever occurs in 26-70% of patients • Infectious vs non-infectious? • 35-55% are thought to be infectious • So, at least 50% of febrile episodes 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. 2 ¡

2/18/15 ¡ 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 • Catheter-Related Bloodstream Infection (CRBSI) • Clostridium difficile Is this non-infectious? 3. • Drug fever • Central fever 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 • CRBSI • ARDS Bloodstream • Candidemia • Endocarditis Cardiac • Pericarditis • Drug Fever • Central fever • DVT/PE • C. Difficile Other non- • Malignancy • CA-UTI infectious • Rheumatologic • Abdominal abscess • Post-op fever etiologies GI/GU • Peritonitis • Transfusion reaction • Acalculous cholecystitis • Transplant rejection • Pancreatitis • Adrenal insufficiency 3 ¡

2/18/15 ¡ Bedside Evaluation Questions to Ask Exam Elements to Include • Any change in secretions or • Careful neuro exam respiratory status? • Sinus exam for nasal • Any diarrhea? discharge or tenderness • Back and joint exam • Skin exam: • Line sites • Decubitus ulcers • Rashes • Remove bandages Case #1 A 55 year old man with CHF and ESRD on HD is admitted to the ICU with decompensated heart failure. He is slowly improving but then spikes a fever to 39 associated with rigors but no other symptoms. He is found to be bacteremic with Klebsiella pneumoniae from both hemodialysis line and peripheral blood cultures. 4 ¡

2/18/15 ¡ Do You Need to Change the Line? Yes 1. No 2. I need more information 3. What Information Would Be Most Helpful? Abdominal CT scan 1. Talk to micro and get the differential time to positivity 2. Examine the line exit site for inflammation 3. 5 ¡

2/18/15 ¡ For Uncomplicated Klebsiella HD-line Infection, IDSA Recommends: Line removal 1. Option for line retention or guidewire exchange 2. CRBSI: Diagnosis Techni hnique Cha haracteristics Clinical Findings Inflammation at the exit site is extremely insensitive (<3%) Mermel et al, Clin Infect Dis 2009, 49:1. Safdar and Maki, Crit Care Med 2002, 30:2632. 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. 6 ¡

2/18/15 ¡ CRBSI: Diagnosis Techni hnique Cha haracteristics Clinical Findings Inflammation at the exit site is extremely insensitive (<3%) Catheter Tip • CRBSI = (+) peripheral bcx and > 15 CFU/plate from catheter tip Culture • 79% sensitive, 92% specific • But >80% of catheters are removed unnecessarily Mermel et al, Clin Infect Dis 2009, 49:1. Safdar and Maki, Crit Care Med 2002, 30:2632. 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. CRBSI: Diagnosis Techni hnique Cha haracteristics Clinical Findings Inflammation at the exit site is extremely insensitive (<3%) Catheter Tip • CRBSI = (+) peripheral bcx and > 15 CFU/plate from catheter tip Culture • 79% sensitive, 92% specific • But >80% of catheters are removed unnecessarily Differential Time • CRBSI = central line bcx turns (+) ≥ 2 hrs before peripheral bcx to Positivity • 85-95% sensitive, 83-90% specific • Allows for diagnosis without removing the line Mermel et al, Clin Infect Dis 2009, 49:1. Safdar and Maki, Crit Care Med 2002, 30:2632. 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. 7 ¡

2/18/15 ¡ CRBSI: Diagnosis Techni hnique Cha haracteristics Clinical Findings Inflammation at the exit site is extremely insensitive (<3%) Catheter Tip • CRBSI = (+) peripheral bcx and > 15 CFU/plate from catheter tip Culture • 79% sensitive, 92% specific • But >80% of catheters are removed unnecessarily Differential Time • CRBSI = central line bcx turns (+) ≥ 2 hrs before peripheral bcx to Positivity • 85-95% sensitive, 83-90% specific • Allows for diagnosis without removing the line Quantitative • CRBSI = cfu from central line bcx is ≥ 3x cfu from peripheral bcx Blood Cultures • Most sensitive and specific but not routinely available Mermel et al, Clin Infect Dis 2009, 49:1. Safdar and Maki, Crit Care Med 2002, 30:2632. 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 ( − ) DTTP ≥ 2 hrs DTTP < 2 hrs Possibili1es ¡ • Contaminant ¡ • Line ¡coloniza1on ¡ ¡ • Bacteremia ¡from ¡other ¡source ¡ Look for with ¡1/2 ¡posi1ve ¡cultures ¡ CRBSI another source 8 ¡

2/18/15 ¡ What about for Candida ? • DTTP cut-off of 2 hours is 85% sensitive, 82% specific • The special case of C. glabrata : • It is the most slow growing Candida with median TTP of 37h (other species 17-29h) • Using 2hr cut-off DTTP: sensitivity 77%, specificity 50% • Optimal DTTP cut-off was 6 hours à sensitivity 63%, specificity 75% Park et al, J Clin Microbiol 2014, 52:2566. When to Remove the Line Complicated Infections Certain Organisms • Severe sepsis • Virulent organisms • Persistent bacteremia (>72h • Staphylococcus aureus of appropriate ABx) • Pseudomonas • Septic thrombophlebitis • Candida • Exit site or tunnel infection/ abscess • Difficult to eradicate (must r/o • Evidence of metastatic contamination) infection: endocarditis, • Micrococcus osteomyelitis • Bacillus • Propionobacteria Mermel et al, Clin Infect Dis 2009, 49:1 9 ¡

2/18/15 ¡ Line Management for Other Organisms Organism PICC/Short-term CVC Tunneled Cath/Port HD Catheter Coag-negative Remove or retain Remove or retain Retain or guidewire staphylococci exchange Enterococcus Remove Remove or retain Retain or guidewire exchange* Other GNRs (not Remove Remove or retain Retain or guidewire Pseudomonas ) exchange* *Assuming uncomplicated infections. Consider removal on a case-by-case basis. Mermel et al, Clin Infect Dis 2009, 49:1 Line Salvage • General principles • Studied primarily in long-term catheters • Treat with antibiotic lock therapy PLUS systemic antibiotics for 7-14 days • Get surveillance blood cultures 1 week after stopping ABx • Antibiotic Lock Therapy • Goal is to 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 10 ¡

2/18/15 ¡ Line Management: Take-Home Points • Differential time to positivity (line positive ≥ 2 hours before peripheral) allows for diagnosis of CRBSI without line removal • All lines should be removed for: • Any complicated infection • Staph aureus, Pseudomonas, or Candida • Difficult to eradicate organisms • Line management for other organisms depends on line type (lower barrier to remove line for short term catheter > long- term catheter > HD catheter) Case #2 A 65 y/o M is admitted with a stroke. 4 days into his hospitalization he spikes a fever to 39, starts coughing, drops his SaO2 to the low 90s on RA, and becomes altered. He is pan-cultured and started on vancomycin and pip/tazo. He improves, and work-up reveals: CXR with a new LLL infiltrate • Blood cultures and sputum culture negative at 48h • UA (from his catheter) shows 30 WBC, Urine cx >100K VRE • 11 ¡