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Objectives
 Discuss initial management of various complex infectiousdisease scenarios
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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
 Fever in the ICU3
 Bone/joint infections4,5
 Endocarditis6
 Intravascular catheter infections7
 Cardiac device infections12
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
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)
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
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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
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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 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
Line infections
 If line infected, remove line
 Especially if:
 Staphylococcus aureus
 Candida species
 Gram negatives
 Duration of therapy from date of line removal:
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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
 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:
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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
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
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 710d of PO anti-staphylococcal antibiotic
 In MOST cases the pocket will need to be debrided and the ENTIRE
device removed
 Consult ID
References
1.
http://www.survivingsepsis.org/Guidelines/Pages/default.aspx
2.
Clinical Infectious Diseases 2011;52(4):e56–e93
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