Interactive Cases. Victor Tseng, MD

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1 Interactive Cases Victor Tseng, MD

3 WHO HAS A NEUTROPENIC FEVER? 61 M ANC T 38.9 being treated for stage IIIA CRC 22 F ANC T 37.0 getting consolidation for ALL 53 F ANC 580 (710 yesterday) + T 38.4 who completed first induction cycle for dose for DLBCL 3 days ago 40 M ANC T 39.0 being treated with ATG/CSA for aplastic anemia 36 F ANC 360 (200 yesterday) + T new RML infiltrate on CXR, having count recovery after second induction cycle for T-cell ALL 83 M with dementia residing in NH who developed dysuria and rigors 2 days prior. Found in ED to have ANC T 39.1 None of the above All of the above

4 WHO HAS A NEUTROPENIC FEVER? 61 M ANC T 38.9 being treated for stage IIIA CRC 22 F ANC T 37.0 getting consolidation for ALL 53 F ANC 580 (710 yesterday) + T 38.4 who completed first induction cycle for dose for DLBCL 3 days ago 40 M ANC T 39.0 being treated with ATG/CSA for aplastic anemia 36 F ANC 360 (200 yesterday) + T new RML infiltrate on CXR, having count recovery after second induction cycle for T-cell ALL 83 M with dementia residing in NH who developed dysuria and rigors 2 days prior. Found in ED to have ANC T 39.1 None of the above All of the above

5 WHO HAS A NEUTROPENIC FEVER? Neutropenia Fever ANC 500 T 38.3 single reading ANC anticipated to nadir 500 in next 48h T 38.0 over 1h

6 BEWARE OF NF MIMICKERS Neutropenia secondary to Sepsis Myeloid Reconstitution (Inflammatory) Syndrome ( MyRIS )

7 Incidence of NF in Solid Tumor and Hematologic malignancies? 5% and 10% 25% and 10% 15% and 50% 25% and > 80% Incidence of a microbiologically provable infection during NF? 10% 25% 50% > 75%

8 Marchetti and Calandra (2002)

9 What are the most common pathogens isolated during NF? Yeast Mold GPC GNR GPR Anareobes Virus What is the most common source/site of infection? HCAP SSTI Unexplained (Sterile) Genitourinary Catheter-Related Infection Endocarditis Enterocolitis (GI)

10 MICROBIOLOGY OF NF

11 MICROBIOLOGY OF NF

12 WHAT FACTOR(S) ARE INVOLVED IN THE PATHOGENESIS OF NF? Decreased Quantity of Neutrophils Decreased Chemotaxis and Phagocytic Activity of Neutrophils Disruption of Mucosal Barrier Direct Bacterial Invasion of Gut Mucosal Layers LPS Endotoxemia Hypothalamic Dysfunction due to Neutropenia

13 WHICH ITEM(S) ARE NOT A PART OF THE VA NEUTROPENIC PRECAUTIONS? Single-Bed Room Neutropenic Diet Flowers Prohibited No PR Medications No Foley Patient wears N-95 outside Reverse Isolation (Full PPE for HCW) HEPA Filter Dedicated Reusable Equipment

14 o You are the hematology fellow taking home call. o Mr. B is a 51 year old AAM with a locally destructive gluteal myxosarcoma, stage IIB. He is has just completed the first cycle of AIM. He has CKD stage 2, COPD stage 3, and obstructive CAD s/p stent placement. o One week after reciecing G-CSF, he calls you at 2 am complaining of rigors, fevers (102 F) and diarrhea.

15 HOW DO YOU RESPOND ON THE TELEPHONE? Take up to four APAP and we ll see you in clinic next week I ll mail you some antibiotics and more G-CSF right away Please come to the ER immediately. You will be admitted to the hospital, and I will see you in the morning Come to the ER now. I will see you there Um Let me call my attending

16 o In the ED, temperature is 38.8, pulse 112, BP 124/48, RR 24 and SpOx 91% on room air. He looks flushed but otherwise is in no distress. He is mentating clearly. o Scattered oral ulcers are noted. R arm port entry is free of erythema. Lungs are clear throghout. He has no murmurs. Abdomen is mildy tender in the RUQ. There are no signs of skin infection. o Stat CBC shows WBC 0.8 with 30% PMN. Creatinine is 1.7. AST and ALT at 310 and 270 respectively. Bicarbonate is 17 with normal anion gap. CXR and cultures are pending.

17 WHERE SHOULD THE PATIENT BE TREATED? Observation (CDU) area of ER Home General Medicine Ward MICU

19 PPV 98.3% NPV 86.4 % SENS 95% SPEC 95% Uys et al. 2004

22 WHICH OF THE FOLLOWING ARE ACCEPTABLE REGIMEN(S) FOR OUTPATIENT THERAPY? Levofloxacin 750 mg PO qd + Augmentin 500/125 mg PO q8h Ciprofloxacin 500 mg PO q12h + Clindamycin 300 mg PO q6h Ceftriaxone 1.5 g IV qd Zosyn 2 g IV q8h Azithromycin 500 mg PO qd + Ampicillin 500 mg q6h Levofoxacin 750 mg PO qd + Vancomycin 1.5 g IV q12h

23 WHICH OF THE FOLLOWING ARE ACCEPTABLE REGIMEN(S) FOR OUTPATIENT THERAPY? Levofloxacin 750 mg PO qd + Augmentin 500/125 mg PO q8h Ciprofloxacin 500 mg PO q12h + Clindamycin 300 mg PO q6h Ceftriaxone 1.5 g IV qd Zosyn 2 g IV q8h Azithromycin 500 mg PO qd + Ampicillin 500 mg q6h Levofoxacin 750 mg PO qd + Vancomycin 1.5 g IV q12h

24 Teuffel et al. Ann Oncol 2011;22:

25 WHAT DIAGNOSTIC TESTS SHOULD BE PERFORMED? BCx from CVC BCx from peripheral vein UA + reflex UCx LP Stool Cx C. difficile toxin assay Nasal Respiratory Virus Swab CXR Mini-BAL

UA is positive for nitrate and bacteria,

26 o CXR shows clear airspaces and normal terminus of catheter tip. Gram stain of BCx reveals numerous GPC in clusters. UA is positive for nitrate and bacteria, negative for LE or WBC. o He is admitted to the floor by the night float medicine intern. M3 PGY-1 PGY-3

28 WHICH OF THE FOLLOWING ARE ACCEPTABLE REGIMEN(S) FOR INITIAL EMPIRIC INPATIENT THERAPY? Zosyn 2 g IV q8h Cefepime 2 g IV q8h Ceftazidime 1.5 g IV q12h + Levofloxacin 750 mg IV qd Vancomycin 1 g IV q8h + Zosyn 2 g IV q8h Vancomycin 1 g IV q8h + Zosyn 2 g IV q8h + Tobramycin 100 mg IV q8h Zosyn 2 g IV q8h + Levofloxacin 750 mg IV qd Cefepime 2 g IV q8h + Voriconazole 250 mg IV q12h Zosyn 2 g IV q8h + Micafungin 100 mg IV qd + Acyclovir 400 mg IV q8h

29 WHICH OF THE FOLLOWING ARE ACCEPTABLE REGIMEN(S) FOR INITIAL EMPIRIC INPATIENT THERAPY? Zosyn 2 g IV q8h Cefepime 2 g IV q8h Ceftazidime 1.5 g IV q12h + Levofloxacin 750 mg IV qd Vancomycin 1 g IV q8h + Zosyn 2 g IV q8h Vancomycin 1 g IV q8h + Zosyn 2 g IV q8h + Tobramycin 100 mg IV q8h Zosyn 2 g IV q8h + Levofloxacin 750 mg IV qd Cefepime 2 g IV q8h + Voriconazole 250 mg IV q12h Zosyn 2 g IV q8h + Micafungin 100 mg IV qd + Acyclovir 400 mg IV q8h

31 WHICH OF THE FOLLOWING IS NOT AN INDICATION FOR EMPIRIC VANCOMYCIN? Clusters of GPC NOS in 1 BCx Pulmonary Infiltrate Hypotension Rigors or Fever during CVC Infusion New Cardiac Murmur NF Occuring During Inpatient Stay Altered Mental Status Suspected SSTI

32 WHICH OF THE FOLLOWING IS NOT AN INDICATION FOR EMPIRIC VANCOMYCIN? Clusters of GPC NOS in 1 BCx Pulmonary Infiltrate Hypotension Rigors or Fever during CVC Infusion New Cardiac Murmur NF Occuring During Inpatient Stay Altered Mental Status Suspected SSTI

33 o Mr. B is started on Vancomycin + Cefepime IV and given a generous IVF resuscitation. o Unfortunately, he continues to spike intermittent fevers, up to 39.2, even after four days of ABx therapy. He has some mild facial congestion but no other localizing symptoms. His ANC remains in a nadir of He remains hemodynamically stable without any evidenceof new end-organ dysfunction from sepsis. o Repeat BCx are growing broadly susceptible CNSA x 1/4

34 WHAT IS YOUR NEXT MOVE? Continue Current ABx Discontinue ABx due to drug fever Broaden to Meropenem IV + Levaquin IV Remove R arm Port and CVC TTE CT Sinus and Chest Start Empiric Antifunal Therapy CT Abdomen MRI Pelvis to assess of Osteomyelitis

35 WHAT IS YOUR NEXT MOVE? Continue Current ABx Discontinue ABx due to drug fever Broaden to Meropenem IV + Levaquin IV Remove R arm Port and CVC TTE CT Sinus and Chest Start Empiric Antifungal Therapy CT Abdomen MRI Pelvis to assess of Osteomyelitis

38 WHEN SHOULD THE CATHETER STAY IN PLACE (i.e. TREAT THROUGH)? BCx grow S. aureus BCx grow P. auruginosa BCx grow MDR E. coli BCx grow ESBL enterobactericiae spp BCx grow Candida spp. Patient develops hypotension Bacteremia 72 hr after taylored ABx therapy Port or Pocket Site Infection

39 WHEN SHOULD THE CATHETER STAY IN PLACE (i.e. TREAT THROUGH)? BCx grow S. aureus BCx grow P. auruginosa BCx grow MDR E. coli BCx grow ESBL enterobactericiae spp BCx grow Candida spp. Patient develops hypotension Bacteremia 72 hr after taylored ABx therapy Port or Pocket Site Infection

40 BONUS QUESTION o A 48 y/o F with late relapsed HL is getting slavage chemotherapy with Stanford V. She had completed her last cycle 8 days ago and develops NF with ANC < 100 and T She has intense R flank and epigastric pain. CT of the abdomen is shown below.

41 WHAT IS THIS? Acute Neutropenic Hepatitis Septic Mesenteric Embolization Abdominal Abscess Neutropenic Necrotizing Enterocolitis Lymphoma

Neutropenic Fever. CID 2011; 52 (4):e56-e93

Neutropenic Fever. CID 2011; 52 (4):e56-e93 Neutropenic Fever www.idsociety.org CID 2011; 52 (4):e56-e93 Definitions Fever: Single oral temperature of 101 F (38.3 C) Temperature 100.4 F (38.0 C) over 1 hour Neutropenia: ANC < 500 cells/mm 3 Expected