1. Benjamin Westley MD FAAP FACP
Module 6: Stewardship in fever/sepsis, neutropenia, osteoarticular infection, and endocarditis
Benjamin Westley MD FAAP FACP
4120 Laurel St Suite 204
Anchorage, AK 99508

2. 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

3. Guidelines Sepsis1 Neutropenia and fever2 Fever in the ICU3
Bone/joint infections4,5
Endocarditis6
Intravascular catheter infections7
Cardiac device infections12

4. 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 bacteremia and/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

5. Fever and neutropenia 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 vancomycin and consider addition of second gram negative drug (e.g. tobramycin)

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

7. 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

8. 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

9. 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 isolator cultures or fungal cultures
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

10. 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)

11. 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

12. 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

13. Bone/joint infection Hematogenous Contiguous Prosthetic joint
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

14. 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

15. 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

16. 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

17. 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

18. 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

19. Endocarditis Duke criteria: 2 major, 1 major and 3 minor, or 5 minor
Multiple positive blood cultures for typical organism
Valvular vegetation or new valve regurgitation
Minor:
Predisposing valve condition or IVDU
Fever >38C
Emboli
Immune phenomena (glomerulonephritis, osler nodes, + RF)
Positive blood culture not meeting major criteria
Abnormal echocardiography without vegetation

20. Endocarditis Get blood cultures first! Preferably 3 sets.
TTE ok for initial imaging; if high suspicion and 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

21. 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

22. References
Clinical Infectious Diseases 2011;52(4):e56–e93
Crit Care Med 2008; 36:1330–1349
Clinical Infectious Diseases 2013;56(1):e1–25
Clinical Infectious Diseases® 2015;61(6):e26–46
Circulation. 2015;132:00-00
Clinical Infectious Diseases 2009; 49:1–45
Journal of Pediatric Orthopedics 1982; 2:255-62
Clinical Infectious Diseases 2009; 48:1201–10
Pediatrics 2009;123;
Pediatrics Oct;130(4):e821-8
Circulation 2010;121;