Objectives Discuss initial management of various complex infectious-

disease scenarios Fever Sepsis Neutropenia and fever Osteoarticular infection Endocarditis

Disclaimer! These patients are complex and generally managed with formal

infectious disease consultation where available The primary role of a stewardship program is typically to ensure an

appropriate empiric regimen and to identify whether further infectious disease consultation might be appropriate

Guidelines Sepsis1

Neutropenia and fever2,13

Fever in the ICU3

Bone/joint infections4,5

Endocarditis6

Intravascular catheter infections7

Cardiac device infections12,14

Empiric sepsis therapy Immediate work-up for source as directed by symptoms

Blood cultures x2 Chest x-ray Urine

If source determined, use appropriate regimen for source and level of illness

If source NOT determined, must consider and treat for occult bacteremiaand/or intra-abdominal source Vancomycin PLUS piperacillin/tazobactam, OR Vancomycin PLUS cefepime PLUS metronidazole Strongly consider need for CT imaging of the abdomen

Some programs use PCT levels to guide initiation and duration of therapy.

If patient improves and no source is found, antibiotics can often be stopped. PCT levels can assist with ensuring it is safe to discontinue in this setting (if f/u level <0.5 or >80% drop from baseline).15,16

Fever and neutropenia Drug induced ANC <500 or <1000 with expected fall <500 AND

temperature >101F or >100.4 for >1 hour

Obtain blood cultures x2

Other workup as directed by symptoms

Cefepime 2g iv q8h ALONE if hemodynamically stable and no source

If source known (lung, skin and soft tissue, abdomen) then use the regimen for NOSOCOMIAL infection E.g. HCAP regimen, or anti-pseudomonal intra-abdominal regimen

If no source and hemodynamically unstable, add vancomycinand consider addition of second gram negative drug (e.g. tobramycin)

Fever and neutropenia If fever persists >4-7 days add antifungal (e.g. micafungin) and

consider imaging workup

Antibiotics are generally continued until the ANC is >500 cells/uL

The following patients should receive ID consultation Neutropenia and septic shock Neutropenia and bacteremia or fungemia Neutropenia and intra-abdominal infection Neutropenia and lung nodules Prolonged neutropenic fever >4-7 days

Determining final regimen construction and duration is challenging and best done with ID assistance

New fever in the hospital Common scenario with multiple possible causes

Nosocomial infection (e.g. IV catheter, CAUTI, HAP) Drug fever DVT Atelectasis Central fever after neurological injury Sinusitis Gout/pseudogout

Work-up PRIOR to antibiotics EXAM!!!! Blood cx x2 CXR or urine as directed by clinical history and exam

New fever in the hospital Most new fevers in the hospital DO NOT require new

antibiotics or a change in prior antibiotic

Workup as directed and await results

If hemodynamically UNSTABLE, then MUST give empiric SEPSIS regimen once evaluation done based on likely source

If a line infection is strongly suspected and patient is unstable, consider removing the line; however, in general, fever in a patient with a central line does not require empiric line removal/line change

Line infections 3 types: Intraluminal, hematogenous, or tunnel/exit site

Controversy regarding culturing IDSA- Culture from each line and peripheral NHSN- Culture from 2 peripheral sites only

Standard cultures are fine Do not need quantitative/isolator cultures or fungal cultures except

in very rare circumstances

If a pathogen grows in the blood, and there is no other obvious source, then it is a line infection

Coag negative staph from a single site is likely a contaminant If it repeatedly grows, then consider real

Line infections If line infected, remove line

Especially if: Staphylococcus aureus Candida species Gram negatives

Duration of therapy from date of line removal: Coagulase negative Staphylococcus: 5 – 7 days Enterococcus and gram negative rods: 7 – 14 days Staphylococcus aureus AT LEAST 14 days (consult ID) Candida species: AT LEAST 14 days from first negative

culture (consult ID)

Line infections If line MUST be salvaged: 2 weeks from negative culture WITH antimicrobial lock

therapy (usually vancomycin) Attempt only with poorly-pathogenic organisms (e.g.

coagulase negative Staphylococcus) Tunneled lines with soft tissue infection of the tunnel tract

CANNOT be salvaged and MUST be removed

Bone/joint infections Hematogenous Most common in children Staphylococcus aureus, Beta-hemolytic strep Gonococcal

Contiguous or innoculation (e.g. wound or trauma) Polymicrobial

Prosthetic joint

Bone/joint infection Hematogenous Vancomycin +/- ceftriaxone AFTER blood and joint cultures

Contiguous Get cultures Probably vancomycin plus something else- highly

individualized

Prosthetic joint Get joint and blood cultures first Vancomycin Add gram negative coverage if hemodynamically unstable or

GNR seen in gram stain

Bone/joint duration of therapy Hematogenous

At least 3 weeks if isolated to joint, guided by clinical, lab, and imaging resolution

6 weeks if concomitant bone infection Parenteral therapy for gram positives Can consider oral quinolones for susceptible GNR Consider ID consult

Prosthetic joint 6 weeks if removed and antimicrobial impregnated spacer placed 3 – 6 months for Staphylococcus species in combination with

rifampin if Debride And Implant Retention (DAIR) is being attempted

Consult ID

Bone/joint in children Virtually always hematogenous

Excellent data that children can be treated with oral therapy once CRP falls and clinically improving8-11

3 weeks for joint, 6 weeks for bone guided by CRP and imaging

Shorter courses probably reasonable9

Outpatient IV therapy and PICC lines are rarely needed for bone/joint infections in children9-11

Vertebral osteomyelitis Native- NO hardware or preceding procedures Monomicrobial, hematogenous S aureus, beta-hemolytic strep, brucella, TB If no sepsis or neurologic impairment, HOLD ANTIBIOTICS

until AFTER tissue obtained for cultures AND pathology IR guided aspiration usually attempted first Send for bacterial, AFB, and fungal cultures

If non-diagnostic, generally repeat by operative technique If no sepsis or neurologic impairment, withhold empiric

antimicrobial therapy until a microbiologic diagnosis is established

If blood grows S aureus, can assume this is etiology and do NOT have to biopsy

Vertebral osteomyelitis Treatment varies by organism

6 weeks of IV therapy vs. highly bioavailable oral therapy

Trend inflammatory markers

Avoid re-imaging unless clinically failing as MRI improvement greatly-lags clinical resolution

These are difficult to treat infections: ID consultation early in the course of workup and management is advised

Orthopedic hardware infections Mono-microbial vs. poly-microbial

Early vs late onset

Unremoved hardware remains a nidus of infection Washout with or without removal, followed by prolonged

systemic therapy If hardware not removed, oral convalescent or suppressive

therapy for a prolonged period may be needed Rifampin generally added for Staphylococcal infections when

hardware remains in place

These are complex infections without easily generalized recommendations: Recommend ID consultation

Endocarditis Modified Duke criteria: 2 major, 1 major and 3 minor, or 5

minor

Major: Multiple positive blood cultures for typical organism Valvular vegetation or new valve regurgitation

Minor: Predisposing valve condition or IVDU Fever >38C Emboli (vascular phenomena) Immune phenomena (glomerulonephritis, osler nodes, + RF) Positive blood culture not meeting major criteria

Endocarditis Get blood cultures first! Preferably 3 sets.

TTE ok for initial imaging but does not rule-out disease; if moderate-high suspicion and TTE negative, do TEE

Vancomycin PLUS ceftriaxone Covers Staphylococcus, Streptococcus, Enterococcus, and HACEK

organisms

Treatment varies by organism, type of valve (prosthetic vs. native)

Gentamicin no longer used for native valve Staphylococcus

Decisions regarding surgical indications are complex

Strongly consider ID consultation

Cardiac device infections Staphylococcus species most common

Categories Superficial/incisional Pocket site Wires/bacteremia

Blood cultures in all cases If bacteremic get TEE

LIMITED superficial skin or incisional infection may be treated with 7-10d of PO anti-staphylococcal antibiotic

In MOST cases the pocket will need to be debrided and the ENTIRE device removed

Consult ID

References1. http://www.survivingsepsis.org/Guideli

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2. Journal of Clinical Oncology 36, no. 14 (May 2018) 1443-1453.

3. Crit Care Med 2008; 36:1330–1349

4. Clinical Infectious Diseases 2013;56(1):e1–25

5. Clinical Infectious Diseases® 2015;61(6):e26–46

6. Circulation. 2015;132:00-00

7. Clinical Infectious Diseases 2009; 49:1–45

8. Journal of Pediatric Orthopedics 1982; 2:255-62

9. Clinical Infectious Diseases 2009; 48:1201–10

10. Pediatrics 2009;123;636-642

11. Pediatrics. 2012 Oct;130(4):e821-8

12. Circulation 2010;121;458-477

13. Clinical Infectious Diseases 2011;52(4):e56–e93

14. Heart Rhythm 2017;14:e503–e551

15. Am J Respir Crit Care Med Vol 177. pp 498–505, 2008

16. Lancet. 2010;375:463-74.