Infectious Diseases Flashcards
High Yield Acronyms/Antibiotics
ESBL – eg E. coli, Klebsiella Rx: Carbapenem, TMP-SMX, FQ, AG (if sensitive)
CPE Rx: Colistin, AG, Tigecycline, Call ID (TMP-SMX or FQ if lucky)
MRSA Rx: Vancomycin, Doxycycline, TMP-SMX, Clindamycin, Linezolid, Daptomycin,
Ceftobiprole
Pseudomonas Rx: Pip/Tazo, Ceftazidime, Cefepime, Imipenem, Meropenem,
Ciprofloxacin, AG, Aztreonam, Colistin, Tigecycline, Ceftazidime-Avibactam,
Ceftolozane-tazobactam
Enterococcus Rx: Ampicillin (if S) or Vanco (not VRE), Linezolid, Daptomycin
Meningitis vs encephalitis ?
MEN:
Predominantly starts with headache,
neck stiffness and fever and can get
altered LOC later into course.
JAMA: Does this adult patient have acute meningitis?
– Meningitis ruled out (99%) if fever, neck stiffness and altered MS all absent
– Jolt accentuation – high sensitivity (97% in one study)
– Kernig’s and Brudzinski’s signs – high specificity, poor sensitivity
* Basal skull meningitis:
– + CN palsies, long-tract signs
– Think TB, Listeria, Cryptococcus, Syphilis, Lyme in correct host
Enceph:
Predominantly starts with altered
LOC/mental status and fever and can
get seizures, focal neurological
changes associated.
Meningitis – Pathogens + Rx
18-50 years -S. pneumoniae, N. meningitidis, H. influenzae
TX =
Vancomycin + Ceftriaxone
> 50 years or
immunocompromised
S. pneumo, N. meningitidis,
H. influenzae, L. monocytogenes
TX:
Vancomycin + Ceftriaxone
+ Ampicillin
***In case of PCN allergy, use Vancomycin + Moxifloxacin +/- TMP-SMX (if Listeria coverage needed)
Empiric VANCO = 15-20mg/kg IV q12h, consult pharmacy for dose adjustments
CSF Gram stains
Gram-positive diplococci → S. pneumoniae
Gram-negative diplococci → N. meningitidis
Gram-negative bacilli or coccobacilli à H. flu
Gram-positive bacilli → L. monocytogenes
Bug specific tx of meningitis
S. pneumoniae :Pen G 4MU IV q4h or
CTX 2g IV q12h 10-14 days Abx
DEX x 4 days
N.meningitidis
H. Flu -CTX 2g IV q12h 4-7 days
L.monocytogenes =Ampicillin 2g IV q4h 21 days
Meningitis - Steroids
Dexamethasone 10 mg IV q6h for 4 days PRIOR TO or WITH first dose of antibiotics ( only use in strep pneumonia)
General approach:
* Administer before or with first dose of empiric antibiotics for suspected
bacterial meningitis
* Stop if CSF is non-turbid OR low cell count OR non-pneumococcal by culture
* Do not start if antibiotics have already been given to patient
Neisseria meningitis – CHEMOprophylaxis
Who?
– Household contacts
– Persons sharing sleeping arrangements
– Persons who have direct nose/mouth contamination w oral/nasal secretions
– Children and staff in childcare or nursery
– HCWs who have had intensive unprotected contact (without wearing a mask) (eg. intubating, resuscitating, closely examining oropharynx)
– Airline passengers sitting immediately on either side of the case (but not across the
aisle) when total time on aircraft > 8 hours
* When?
– Within 10 days usually
* What?
– Ciprofloxacin 500mg PO X 1 dose (increasing resistance concern)
– OR ceftriaxone 250mg IM X 1 dose
– OR rifampin 600mg PO BID X 2d
N. meningitis – IMMUNOprophylaxis
Who?
– Household contacts of a case of invasive
meningococcal disease (IMD)
– Persons sharing sleeping arrangements with a case
of IMD
– Persons who have direct nose/mouth contamination
with oral/nasal secretions of a case with IMD
– Children and staff in contact with a case of IMD in
childcare or nursery school facilities
* What?
– Depends on serotype of index case and
age/underlying conditions of contact
– Men-C-ACYW or 4CMenB can be considered
Healthcare–Associated
Ventriculitis & Meningitis
Signs and Symptoms
* New headache, nausea, lethargy, altered LOC
* Erythema and pain over SC shunt tubing
Investigations
* Blood cultures, CSF culture including fungal culture (hold for 10 days)
Management
1. Complete removal of infected CSF shunt / hardware, replaced with external drain
2. Empiric Treatment: Vancomycin PLUS Ceftazidime OR Meropenem
– +/- Rifampin (if staphylococcal isolate)
– +/- intraventricular Abx if no response to systemic Abx
3. Repeat CSF cultures to confirm negative growth
– Duration of therapy 10-14 (gram positives) up to 21 days (gram negatives) from last positive culture
4. Reimplantation of new shunt once repeat CSF culture have been negative for 7-10 days
Infective Endocarditis- diagnostic work-up
Diagnostic workup
– at least 2 sets of blood cultures prior to antibiotics (3 in 2015 IE statement)
– Initial TTE for everyone.
* TEE Class I indications: TTE nondiagnostic or IE complications suspected or intracardiac
leads (TEE widely used these are just the Class I – eg consider if staphylococcal,
enterococcal, fungal infections)
In patients being considered for an early change to oral antibiotic therapy
for treatment of stable IE, baseline TEE before switching to Oral and repeat
TEE 1-3 days before completing antibiotic regimen should be performed
IE – Diagnosis (Duke Criteria)
MAJOR (M)
Microbiological Evidence
A) Microbiologic Criteria (≥1 of):
- ≥2 BCx with typical organisms:
- S. aureus/lugdunensis, Streptococci (except GAS or pneumo), E.
Faecalis, HACEK, Granulicatella, Abiotrophia, Gemella in Native Valve
- ≥3 BCx with occasional/rare organisms
- Blood PCR for Coxiella, Bartonella, T. whipplei
- Coxiella burnetii in 1 BCx or IgG > 1:800
- Bartonella henselae or quintana IgG > 1:800
B) Imaging Criteria
- Echo or Cardiac CT: vegetation, valve/leaflet perforation or
aneurysm, abscess, pseudoaneurysm, fistula, prosthetic valve
dehiscence or New significant valvular regurgitation
- PET: Abnormal activity of valve, aortic graft, or intracardiac leads
C) Surgical Criteria
- Evidence of IE by direct inspection during surgery
Minior:
Predisposition: Prior IE, Prosthetic Valve, Prior Valve Repair, Congenital
heart disease, Regurgitation/Stenosis, Pacemaker/ICD, HOCM, IDU
Fever: Documented temp >38
Vascular Phenomena: Arterial emboli, septic pulmonary infarcts,
cerebral or splenic abscess, mycotic aneurysm, ICH, conjunctival
hemorrhage, Janeway lesion, purulent purpura
Immunologic Phenomena: Rheumatoid Factor, Osler Nodes, Roth
Spots, immune-complex GN
Microbiologic Evidence: BCx for organism consistent with IE not
meeting major criteria, BCx/PCR with organism consistent with IE from
sterile body site, PCR for skin bacteria on valve/wire
Imaging Criteria: Abnormal activity on PET within 3m of implant of
prosthetic valve, aortic graft, intracardiac leads, prosthetic material
Physical Exam Criteria: New Valve regurgitation on auscultation
DEFINITE IE
- Microorganism identified on vegetation/valve
- 2M OR 1M+3m OR 5m criteria
POSSIBLE IE
- 1M+1m OR 3m criteria
REJECTED IE
- Alternative Diagnosis
- Lack of recurrence with <4d Abx
- Negative pathology with <4d Abx
- Does not meet Possible IE criteria
IE – Treatment New Class IIb recommendation in 2021
In patients with left sided IE caused by Streptococcus, E. faecalis, S. aureus or CNST
deemed stable by the multi-D team. Team after initial IV antibiotics, a change to
oral abx therapy may be considered if:
– TEE before the switch to oral therapy shows no paravalvular infection AND
– Frequent and appropriate follow-up can be assured by the care team, AND
– If a follow-up TEE can be performed 1-3 days before the completion of the abx course.
IE - Prophylaxis
Patient population :
Prosthetic cardiac valve (including TAVI,
devices e.g. annuloplasty ring, clips, LVAD)
*Not indicated for PPM/ICD, coronary stent
Previous IE
Congenital Heart Disease
Cyanotic CHD, unrepaired
- CHD repair with patch/prosthetic within 6
months
- CHD with residual defect near
patch/prosthetic
Cardiac transplantation recipients who
develop cardiac valvulopathy
Dental procedures involving gingival manipulation,
manipulation of the periapical tissue and perforation of oral mucosa
Respiratory tract procedures WITH transection of resp mucosa eg tonsillectomy , adeniodectomy
Any piercing of infected skin (e.g. biopsy of rash)
Regimen (give 30-60 min before dental or respiratory procedures procedure):
- Amoxicillin 2g PO x1, NPO → Ampicillin 2g IV/IM OR cefazolin/ceftriaxone 1 g IV/IM
- PCN allergy → Cephalexin 2g PO OR azithro 500mg PO OR doxycycline 100mg PO
- NPO + PCN allergy → Cefazolin/ceftriaxone 1g IV/IM - For skin and respiratory tract procedures, consider which what organism may be causing specific
Community Acquired
Pneumonia (CAP)- Pathogens
Common pathogens:
– S. pneumoniae (most common)
– M. pneumoniae
– C. pneumoniae
– H. influenzae
– Respiratory viruses (Influenza,
RSV, parainfluenza, rhinovirus,
adenovirus, coronaviruses…)
- Severe disease
– Legionella pneumophila
In patients with increasing comorbidities,
antibiotic and hospital exposures:
– Increasing gram negatives e.g. K. pneumoniae,
Pseudomonas (PsA)
– S. aureus (including MRSA)
* post-influenza pneumonia
CAP – Diagnostics
Do not obtain sputum or blood C&S on outpatients (yield low)
- Consider for inpatients if severe CAP / intubated/ being treated empirically for MRSA or
Pseudomonas
- Consider urine pneumococcal + legionella Ag +/- lower tract Legionella NAAT in severe
CAP or when indicated by epidemiological factors (e.g. outbreak)
- Send rapid influenza molecular assay (NAAT) when influenza virus is circulating in
community
- In severe CAP or immunocompromised patients, can also send NAAT for non-influenza viruses
CAP – Outpatient Treatment
Healthy outpatients without comorbidities or risk factors
– Amoxicillin 1 g TID (strong, moderate)
– Doxycycline 100 mg BID (conditional, low)
– Azithromycin 500 mg and then 250 mg (or Clarithromycin) - only in areas with pneumococcal
resistance < 25% (conditional, moderate)
* Not appropriate for majority of Canada
Outpatients with comorbidities (chronic heart, lung, liver, renal, diabetes, alcoholism, malignancy, or asplenia)
– Amox-clav OR Cephalosporin (Cefpodoxime, cefuroxime) PLUS macrolide (strong, moderate)
OR Doxy (conditional, low)
– Resp FQ ie. levofloxacin/moxifloxacin(strong, moderate)
CAP – Inpatient Treatment
Inpatients, non-severe, without risk factors for MRSA or PsA
– Beta-lactam (CTX, amp-sulbactam, cefotaxime, or ceftaroline) PLUS Macrolide (strong, high).
* Beta-lactam + Doxy is a third line option as alternative if unable to macrolide or FQ (conditional, low), but this is not first line because legionella has higher rates of resistance to doxycycline than Macrolide or FQ
– Resp FQ (levofloxacin, moxifloxacin)
Inpatients, severe CAP, without risk factors for MRSA or PsA
– Beta-lactam PLUS Macrolide (strong, moderate)
– Beta-lactam PLUS Resp FQ (strong, low)
* Evidence that macrolide containing combination had lower risk of death, and evidence that combination
of beta-lactam and Resp FQ had higher mortality (but poor quality evidence/small number of
observational trials)
- Aspiration Pneumonia – recommend AGAINST adding empiric anaerobic coverage
unless empyema or abscess present (conditional, low quality)
CAP – Other
Consider MRSA coverage based upon local risk factors
– Vancomycin 15 mg/kg IV q12h or linezolid 600 mg q12h
– Consider severe post-influenza pneumonia, mechanical ventilation/ICU, significant recent antibiotic
Consider Pseudomonas coverage based upon locally validated risk factors
– Pip-Tazo or Cefepime 2g q8h or Ceftaz 2g q8h or Aztreonam or Meropenem 1g q8h
– Usually recent mechanical ventilation OR prior isolation of organism.
Transition to PO
– Hemodynamically stable, improving, tolerated PO/absorbing from GI
Duration of Treatment – 5 days if afebrile x 48 hrs with ≤ 1 sign of CAP clinical instability (HR>100, RR>24, SBP<90, paO2<90%,
can take PO, normal mental status)
Steroids? – No longer recommended unless refractory shock
HAP/VAP- pathogens
Microbiology
* Core pathogens = S. pneumoniae,
MSSA, H. influenzae, GNB including
Pseudomonas
Diagnosis
* Diagnosis based on clinical criteria alone
* Obtain non-invasive respiratory samples
* CPIS score and inflammatory markers
NOT recommended by IDSA
* Tracheobronchitis v. VAP
HAP/VAP- Empiric Treatment
Empiric Treatment: One of Column A +/- Column B +/- Column C
Column A:
Base –
Pseudomonas +
MSSA coverage
- PipTazo
- Cefepime
- Imipenem/Meropenem
- Levofloxacin*
Column B:
MRSA coverage
If risk factors for MRSA (>20%
prevalence) or mortality
- Vancomycin
- Linezolid
Column C:
2nd Anti-pseudomonal agent
(use different class than base)
If >10% resistance to base drug, or if risk factor for
Pseudomonas resistance
- Ceftazidime/Cefepime/PipTazo/Mero/Imipenem
- Ciprofloxacin/Levofloxacin
- Aminoglycoside (less preferred)
- Colistin (less preferred)
duration= 7 days
Influenza- who to test, who to treat , how to treat
When Influenza is circulating in community:
– Symptomatic outpatients if will influence
treatment
– All inpatients with acute respiratory illness
* When influenza is not circulating:
– Symptomatic inpatients with epidemiologic link to
influenza case
– Consider in high-risk patients with acute
respiratory symptoms
Who to Treat?
* Any patient hospitalized with influenza
* Any Outpatients with severe/progressive illness or risk
factors
– >65, pregnant or 2 weeks post-partum,
immunocompromise, comorbidities
* Consider in other outpatients <2 days onset or with
high-risk household members
How to treat?
* Start Neuraminidase inhibitor as soon as possible
– E.g. Oseltamivir 75mg BID for 5 days
* Benefit: Resolution of symptoms ~1 day sooner
* Harms: Nausea/vomiting
– Can treat for longer in immunocompromise or severe disease
* No steroids or immunomodulators
When to consider bacterial co-infection?
* Initial Severe disease (extensive pneumonia, respiratory failure,
hypotension)
* Deterioration after initial improvement with antivirals
* Consider if not improving with 3-5 days of antivirals
Prophylaxis:
* In institutional outbreaks, daily oseltamivir for all patients (+/- unvaccinated staff) on impacted wards until 7 days from last case
* Post-exposure prophylaxis (Oseltamivir daily x 7d) can be considered in
high-risk household contacts within 48hrs
Diarrhea: Diagnosis
Stool cultures for Salmonella, Shigella,
Campylobacter, Yersinia, STEC in patients
with diarrhea AND:
– Fever
– Bloody or mucoid stools
– Severe abdominal pain
– Sepsis
– Immunocompromise or outbreak exposure
– (V. Cholerae in large volume rice water stools)
C. difficile testing in patients with:
– Recent antibiotics
– Work in healthcare/LTC or prison
– Compatible syndrome
– IBD flare
Blood cultures in patients with:
– Immunocompromise
– Sepsis
– Suspicion of enteric fever
* Stool for Ova and Parasites in patients with:
– Diarrhea ≥ 14 days
– Immunocompromise e.g. HIV
– Travel
– Increased yield if ordered daily x 3 days
– Repeat up to 3x to increase yield if high suspicion
Diarrhea - Treatment
Empiric therapy in adults with bloody
diarrhea not recommended UNLESS:
1. Sick immunocompetent patients with
bacillary dysentery (frequent scant
bloody stools, abdominal pain, tenesmus,
fevers), suggestive of Shigella
2. Recent travel with high fever (≥ 38.5)
and/or sepsis
3. Sick immunocompromised patients
* Empiric antibiotic choice: ciprofloxacin
or azithromycin
* May use loperamide; caution if bloody
stool, fever
C. difficile Infection (CDI) Diagnosis
Testing:
– Stool toxin test - combinations
* EIA for GDH, toxin
* NAAT PCR for toxin
– Pseudomembranes on colonoscopy
- Clinical Syndrome:
– Unexplained new-onset ≥3
unformed stools in 24 hours - C. difficile colonization: Positive C.
diff stool test in absence of clinical
syndrome - Criteria for severe C. difficile:
– WBC > 15 OR serum Cr 1.5 x pre-
morbid level
– Other risk factors: Age > 65,
immunosuppression, T > 38,
Albumin < 30
- Fulminant C. difficile:
– Sepsis, Shock, Ileus, perforation,
toxic megacolon (colon dilation
>6cm)
C. difficile Infection First Episode Treatment
- Determine colonization vs infection (based on clinical picture)
- STOP non-essential antibiotics! Stop PPI if not needed! No evidence for probiotics.
- Fidaxomicin similar response but less recurrence after 1st episode, but expensive (not often covered)
1st episode
(non-fulminant)
Fidaxomicin 200 mg PO BID x 10d
Vancomycin 125mg PO QID x 10d
(10-14d for AMMI)
Metronidazole 500mg PO TID x 10-
14d (non-severe only)
1st episode
(Fulminant)
Vancomycin 500 mg PO/NG QID + IV
metronidazole 500 mg Q8H
+/- PR vancomycin
+/- Total colectomy
C. difficile Infection Recurrence Treatment
First relapse
(Within 3
months of
previous
infection)
Fidaxomicin 200mg PO BID x 10d
OR BID x 5d then q2d x 20d
Vancomycin Taper + Pulse
Vancomycin 125mg PO QID x 10d (14d)
Metronidazole 500mg PO TID x 10-14d
Bezlotoxumab 10mg/kg IV x 1
≥2nd relapse Fidax 200mg PO BID x 10d OR BID x 5d then q2d x 20d
Vancomycin Taper + Pulse
Vanco 125mg PO QID x 10d then Rifaximin 400mg x 20d
Bezlotoxumab 10mg/kg IV x 1
FMT (≥3 episodes)
Oral Vancomycin Suppression
Risk factors for recurrence
* Recurrent CDI in last 6m
* age>65
* Immunocompromised
* severe CDI on
presentation
Intraabdominal Infections (IAIs)
- Adequate source control is #1 principle of management
– Percutaneous if possible, laparotomy otherwise.
– Collections 3cm or smaller can be attempted to be managed with antibiotics alone - Initial antimicrobial coverage
– Community-acquired, no previous hospitalization (E. coli, B. fragilis) -> Ceftriaxone or
ciprofloxacin PLUS metronidazole (OR Amox-Clav)
– Healthcare-associated or critically ill (Pseudomonas coverage) -> Piptazo, meropenem,
ceftazidime OR cipro PLUS metronidazole
- Enterococcal coverage for healthcare-associated or severe biliary infection, immunocompromise, post-operative infection or intravascular prosthesis/valvular heart
disease. (Amox-Clav, PipTazo, Imipenem, Vanco)
– Targeted antifungal coverage recommended for severe or nosocomial IAI if Candida isolated
from intraabdominal or blood cultures. Empiric coverage otherwise dose not improve
mortality.
- STOP-IT Trial (2015): If source control achieved, 3-5 days of antibiotics has similar
outcomes to continuing until 2 days after resolution of fever, leukocytosis, and ileus.
Complicated UTI
OR Pyelonephritis (Oral)
Ciprofloxacin 500mg x 7 days
TMPSMX 1 DS BID x 7-14 days
Complicated UTI
OR Pyelonephritis (IV)
Base on local antibiogram
Ceftriaxone 1g q24h
Ciprofloxacin 400mg BID
Gentamicin +/- Ampicillin
Alternatives:
Pip-Tazo 3.375g q6h if history of resistance
Carbapenem if history or resistance
Prostatitis
- E. coli, Other Enterobacteriaceae, Pseudomonas
- Occasionally Enterococci, S. Aureus
- Do not treat if asymptomatic unless elevated PSA, planning for biopsy or infertility
- Acute: fever, dysuria, pelvic pain, tender and edematous prostate
– Obtain urinalysis + culture prior to abx
– Abx – empiric piptazo, 3rd gen ceph, FQ
– Duration 2-4 weeks - Chronic, bacterial: Subtle. Recurrent UTIs, obstructive symptoms.
– Ucx with prostatic massage
– Abx – FQ or TMPSMX based on susceptibility
– Duration 4-6 weeks if FQ, 8-12 weeks if other abx
Gonorrhea/Chlamydia Treatment
Gonorrhea Ceftriaxone 250mg IM x 1
(Alt: Cefixime 800mg PO x 1)
PLUS
Azithromycin 1g PO x 1
(Alt: Doxycycline 100mg PO BID x 7d)
Alternative :
Ceftriaxone 500mg IM x 1
(Doxycycline added only if
Chlamydia cannot be ruled out)
For DGI:
Ceftriaxone 1-2g IM/IV q24h x 7 days
TOC of cure 2 weeks after treatment
for all infections (PHAC)
Chlamydia Azithromycin 1g PO x 1
OR
Doxycycline 100mg PO x 7 days
For LGV:
Doxycycline 100mg PO BID x 21 days
Indications for TOC (3-4w after
treatment) :
- LGV
- Unclear compliance
- Alternative regimen
- Pregnancy
Syphilis-tx
PRIMARY, SECONDARY, EARLY LATENT:
Benzathine penicillin G 2.4 mU IM x 1
ALTERNATIVE (limited evidence):
* Doxycycline 100mg BID x 14d
* Ceftriaxone 1g IM/IV x 10d
LATE LATENT or UNKNOWN DURATION, TERTIARY
SYPHILIS:
Benzathine penicillin G 2.4 mU IM weekly x3
ALTERNATIVE:
* Doxycycline 100mg BID x 28d
* Ceftriaxone 1g IM/IV x 10d if carefully monitored
NEUROSYPHILIS
Aqueous penicillin 4mU q4 hours IV x 14 days
ALTERNATIVE:
* Preferably desensitize
* Ceftriaxone 1-2g IM/IV x 10-14d With specialist
For PCN allergy, consider desensitization
for:
Pregnancy, Neurosyphilis
Skin and Soft Tissue Infections (SSTIs)-purulent vs non-purulent
PURULENT
* Folliculitis: Infection of isolated hair
follicle
* Furuncle: Infection on hair follicle
extending into dermis + SC tissue
* Carbuncle: Coalescence of several
infected follicles
* Abscess: Collection of pus within
dermis + SC tissue
NON-PURULENT
* Impetigo: Most often caused by S.
aureus
* Erysipelas: Most often caused by
GAS, infecting epidermis + dermis
* Cellulitis: Most often caused by GAS,
infecting epidermis + dermis + SC
tissue
* Necrotizing fasciitis: see later slides
Managing SSTIs: Purulent
- Purulent (Furuncle/Carbuncle/Abscess)
– I&D and C&S should be performed
Mild Consider antibiotics based on clinical context**
Moderate
(systemic signs of infection)
Cephalexin* or
TMP/SMX or
Doxycycline
MRSA → TMP/SMX
MSSA → Cephalexin
Severe
(IC, failed prior antibiotics or I&D,
systemic signs of infection)
Vancomycin MRSA → Vancomycin
MSSA → Cefazolin
Managing SSTIs: Non-Purulent
- Non-Purulent (Impetigo/Erysipelas/Cellulitis) – Think Strep!
Mild
(no systemic signs of infection; no
focus of purulence)
Oral cephalosporin
(cephalexin)
Moderate
(systemic signs of infection)
IV cephalosporin
(cefazolin)
** Consider antimicrobials effective against MRSA (and streptococci) if cellulitis is associated with penetrating trauma, evidence of MRSA infection elsewhere, nasal colonization with MRSA, PWID
*** If patient is severely immunocompromised, consider broadening coverage to Vanco + PipTazo OR Vanco + Meropenem/Imipenem
Recurrent Cellulitis Trials
BOTTOM LINE: Guidelines suggest considering
trial of oral penicillin ( ? 1 year) if ≥3/ year DESPITE
controlling other risk factors (e.g.
revascularization, wound care, foot wear,
compression, tinea)
- BOTTOM LINE: Compression therapy for
patients with chronic leg edema and recurrent
cellulitis as part of first line prevention
measures
Erythema with systemic toxicity, gangrene/anesthesia, hard induration, hemorrhagic bullae,
pain-out-of-proportion and extending beyond erythema
– EMERGENT surgical inspection/debridement to rule out necrotizing process
(SURGERY CONSULT – This is a surgical emergency)
– EMPIRIC Abx: PipTazo + Vancomycin + Clindamycin
– Consider IVIG if shock or pre-operative
GAS (S. pyogenes)
(TYPE 2 NF)
PCN + clindamycin
Polymicrobial
(TYPE 1 NF)
PipTazo + vancomycin
or carbapenem
Clostridium spp. PCN + clindamycin
Toxic Shock Syndrome (TSS): Group A Strep- dx and tx
(and sometimes S. aureus – tampons, nasal packing)
Diagnostic Criteria:
* Hypotension (sBP < 90) AND
* Isolation of GAS from normally sterile
site
AND at least two of the following:
– Renal impairment (Cr > 177)
– Coagulopathy (plt < 100 or DIC)
– Liver fx abnormality (ALT/AST/Tbili 2X
Upper limit of normal)
– ARDS
– Generalized erythematous macular rash
that may desquamate
Management:
* Contact and droplet precautions*
* Volume resuscitation
* Surgical source control (especially if
necrotizing SSTI suspected)
* Antibiotics: Beta lactam PLUS
clindamycin
* IVIG – limited evidence but consider if
severe infection
* Hyperbaric O2 (HBO)–efficacy unknown
* Chemoprophylaxis – cephalexin x10d
(clinda if PCN allergy)*
Osteomyelitis
Etiology
* Hematogenous (more common in children [long bones] vs. adults [vertebrae]) à
monomicrobial
* Contiguous from SSTI, trauma, or surgery (more common in adults) à polymicrobial
Non-Vertebral Osteomyelitis (w/o hardware) - dx and tx
Investigations
Blood Cultures
Appropriate Imaging
CRP
Bone Biopsy/OR Specimen if possible
Empiric Therapy Ceftriaxone +/- Vancomycin (if MRSA risk factors) +/- Metronidazole (if sacral)
Tailor based on organism if possible
Duration 6 weeks from last debridement if residual infection
48 hours post complete source control
if hematogenous spread:
4-6 weeks
Chronic Wounds
- What type of foot ulcer is it?
– Neuropathic: Pressure points, punched out appearance, deep ulcer,
minimal pain, warm and dry foot
– Arterial: Lateral malleolus, dry and punctate, decreased pulses, cold and
dry foot
– Venous: Medial malleolus, irregular margins, shallow depth, mildly
painful, venous stasis dermatitis/lipodermatosclerosis
- Is the ulcer infected?
– Pain in chronic wound (LR 11-20)
– Foul odour (LR 1-3)
– Purulence, exudate, erythema, warmth, and edema (LR < 1.0)
Diabetic Foot Infection
Diagnosis: Diagnose soft tissue infection clinically
* CRP +/- ESR +/- Procalcitonin if equivocal exam
* Combination of probe-to-bone, plain x-rays and CRP/ESR to diagnose
osteomyelitis; send MRI if diagnosis in doubt
* If possible obtain samples from tissue specimen (soft tissue) or bone biopsy
(osteomyelitis) for culture
* Stage using the IWGDF/IDSA classification (do not memorize!)
* Consider hospitalizing patients with severe infection or mod infection w/
comorbidities
Surgery and Debridement
* Urgent Surgical consult if severe or moderate DFI with complications, early surgery
to remove infected and necrotic tissue
* Consider surgery in patients with osteomyelitis or PAD with ulcer, gangrene
* Exception: Forefoot osteomyelitis only, no PAD, no exposed bone and no need for
surgery to control infection
Revascularization
- Obtain vascular consult for DFI w/ PAD for consideration of revascularization
Other Pillars of Multidisciplinary Management
* Wound Care
* Glycemic Control
* Off-loading + Foot care (Chiropodist, shoe care)
Native Vertebral Osteomyelitis
- Microbiology:
– Most common S. aureus*
– Beta-hemolytic streptococci, GNB
– TB, Brucella, fungi much less common - Risk factors:
– Elderly, immunocompromised, IDU, PICC/Ports - Signs and symptoms:
– New/worsening back pain and suggestive b/w
– Fever (only 45% of patients) - Diagnosis:
– Blood cultures (50% Pos if S. aureus), biopsy
– ESR, CRP (sensitivity 94-100%)
– MRI (SN 97%, Sp 93%)
Tx:
– Hold ABx until biopsy result if no sepsis/neuro
compromise (dx 50-60% of time with 1st bx)
– Empiric: ceftriaxone + vancomycin
– Duration: 6 weeks
– Surgery if neuro deficits, spinal cord compression,
progression/recurrence despite appropriate
antibiotics
- Follow-up:
– Monitor clinically and repeat inflammatory markers
– Repeat MRI ONLY if poor clinical response after ABx
HIV – Initiation of ARV
- Assess readiness for treatment
- ARV recommended for all individuals with HIV, regardless of CD4 count to reduce morbidity and mortality associated with HIV infection
- ARV regimen should include TWO (sometimes one) NRTIs PLUS INSTI OR NNRTI OR PI
First Line Therapy:
* Bictegravir/tenofovir alafenamide/emtricitabine
* Dolutegravir PLUS:
Ø Tenofovir alafenamide/emtricitabine
Ø Tenofovir disoproxil fumarate/emtricitabine
Ø Tenofovir disoproxil fumarate/lamivudine
* Dolutegravir/lamivudine with caveats
* (Dolutegravir/Abacavir/Lamivudine with caveats)
Tenofovir alafenamide (TAF) has fewer
bone and renal toxicities, whereas
tenofovir disoproxil fumarate (TDF) is
associated with lower lipid levels and
lower cost
HIV – OI Primary Prophylaxis (1) PJP
<200 PJP
- TMP/SMX 1 DS PO daily (AI)
- TMP-SMX 1 SS PO daily (AI)
Alternative
- TMP-SMX 1 DS PO M/W/F (BI)
- Dapsone (check G6PD)
- Atovaquone ($$$) 1500mg PO daily
- Aerosolized pentamidine monthly
(infrastructure)
Prophylaxis with TMP-SMX recommended during pregnancy – supplement with folic acid
during first trimester (NT defects)
Continue prophylaxis until CD4 count stabilizes >200 for at least 3 months
HIV – OI Primary Prophylaxis (2) - Toxoplasma and MAC
<100 Toxoplasma (if
Toxo IgG positive)
- TMP/SMX 1 DS PO daily (AI)
Alternative:
* TMP-SMX 1 DS PO M/W/F (BIII)
* TMP-SMX 1 SS PO daily (BIII)
* Dapsone + pyrimethamine (+ leucovorin) (BI)
* Atovaquone (CIII) ($$$)
<50 MAC
* Azithromycin 1200 mg PO weekly
* Clarithromycin 500mg PO
BID
Alternative:
- Rifabutin
HIV – OI Treatment (1)
PJP TMP-SMX 15-20mg/kg IV [TMP
component] x21 days (Any severity)
PLUS (FOR SEVERE ONLY):
* Prednisone 40mg PO BID x5d then
* 20mg PO BID x5d then
* 20mg PO OD x11d
Alternatives:
Moderate to Severe
* Primaquine* + Clindamycin IV
* Pentamidine IV
Mild to Moderate
* Dapsone* + TMP
* Primaquine* + Clindamycin PO
* Atovaquone 750mg PO BID
- Check G6PD prior to using dapsone or primaquine
Note: Septra is considered probably safe for G6PD and CAN be used (though most providers avoid it) - Add leucovorin when using pyrimethamine
HIV – OI Treatment (2) Toxo, MAC
Toxoplasma Sulfadiazine + pyrimethamine (AI) x 6wk
(acute infection) +/- chronic maintenance
if ongoing clinical or radiographic disease
Alternative:
- Pyrimethamine + clindamycin (AI)
- TMP-SMX 10mg/kg/day (BI)
- Atovaquone + sulfadiazine
- Atovaquone + pyrimethamine
- Atovaquone
MAC Clarithromycin + ethambutol OR
Azithromycin + ethambutol x12 mos
- Consider adding rifabutin,
amikacin, FQ if advanced HIV or
severe disease
HIV in Pregnancy
- Vertical transmission in untreated women is 25-35%, <1% with effective treatment
- All HIV + women contemplating pregnancy need ARV and undetectable VL prior to
conception
– Goal of ARV= undetectable VL throughout pregnancy - Intra-partum care
– Always continue ARV
– If VL > 1000 copies/mL (or unknown) near delivery, give IV zidovudine and
recommend scheduled C/S
– If VL suppressed, no increased risk of vaginal delivery - Post-partum care
– If maternal VL suppressed within 4 weeks of delivery: Infant given AZT x 4wks
– If maternal VL not suppressed at birth, infant given presumptive 3-drug ART
– Breastfeeding NOT recommended for mothers living with HIV in [US/Canada],
as safe alternatives are available but woman who choose to breastfeed can be
supported
ARV in Pregnancy
Dolutegravir, previously thought to increase risk of neural tube defects, has been shown to have
very low (but not zero) risk of NTD, and is now a preferred drug in pregnancy due tolerability and
efficacy *
Update: TAF now accepted/preferred for pregnancy
- ABC/3TC/DTG is only single tablet preferred regimen in pregnancy in Canada (Dolutegravir (DTG) + Abacavir (ABC) + Lamivudine (3TC)
- If a woman is already on a different regimen when she becomes pregnant, do not change regimen
- Counsel patients on risks of NTD * Folic Acid for all patients.
Latent TB – testing methods
- Two accepted tests: TST and IGRA
- Neither can separate LTBI from active TB
Decision to test= decision to treat – only check if high risk/occupationally indicated
TST – Tuberculin Skin Test IGRA – Interferon Gamma Release Assay
* In vivo
* May be affected by BCG after infancy
* 2 patient visits
* Inter-reader variability
* Sensitivity 90%; Specificity >95% if no
BCG, 60% with BCG
* Cheap - use if repeat testing required
* May be (-) if immunosuppressed
IGRA – Interferon Gamma Release Assay
- In vitro
- Not affected by BCG - use if prior BCG
- 1 patient visit - use if unlikely to return
- Minimal inter-reader variability
- Sensitivity 80-90%; Specificity >95%
- Often not covered ($$ to patient)
- May be (-) if immunosuppressed
Latent TB – Diagnosis
Who should be tested?
Those likely to be exposed and/or at elevated risk of developing TB Disease and
would therefore benefit from treatment.
E.g.
* Contacts of active case of pulmonary TB
* Immigrants from countries with high TB incidence with risk factors for reactivation
* Planned future start of immunocompromising medications (e.g. chemotherapy, TNF-a
inhibitors, steroids), especially if other risk factors
* People living with HIV
Sometimes may also test those with elevated risk of exposure and contact with
vulnerable populations e.g. healthcare workers
0-4mm Generally considered negative
5mm (higher pre-test
probability)
People living with HIV
Contact with infectious TB case within past two years
Presence of fibronodular disease on CXR (evidence of healed, untreated Tb)
Prior to Organ transplantation (ie. Immunosuppressive rx)
Planned Biologic use including TNF-alpha inhibitor use or DMARDs
Planned other immunosuppressive drugs (incl corticosteroids >= 15 mg per day for at
least 1 mon.)
Stage 4 or 5 CKD (with or without dialysis)
> 10mm
All other situations (ie. DM even if well controlled, malnutrition (<90% ideal body wt),
silicosis, hematologic malignancies, certain carcinomas (Head and Neck, Lung and/or GI
tract), cigarette smoking, alcohol consumption > 3 drinks/d), TST conversion (within 2
years)
- Interpret TST (Positive Predictive
Value) - Exclude active disease
- Determine risk of re-activation
- Consider risk of AEs
FIRST LINE REGIMENS
Rifampin (4R) Daily 4 Months Rash, Drug Interactions
Rifapentine + Isoniazid (3HP) Weekly 3 Months Flu-like effects, drug interactions
SECOND LINE REGIMEN
Isoniazid (9H) Daily -9 Months Hepatotoxicity, peripheral neuropathy
ALTERNATIVE REGIMENS
Isoniazid (6H) Daily -6 Months Hepatotoxicity, peripheral neuropathy
Isoniazid Twice Weekly -9 Months Hepatotoxicity, peripheral neuropathy
Isoniazid + Rifampin (3HR) Daily -3 Months Hepatotoxicity, peripheral neuropathy,
Drug interactions
TB DISEASE Treatment Standard Regimen for Suspected* Drug Susceptible TB
INTENSIVE PHASE (2 Months)
INH 5 mg/kg (up to 300mg)
RMP 10 mg/kg (up to 600mg)
PZA (Pyrazinamide) 20-25 mg/kg
EMB 15-20 mg/kg
-Intensive Phase = 3 or 4 active drugs for rapid killing
-Continuation Phase = at least 2 active drugs, duration
dependent on regimen, adherence, site of infection,
response
-Add B6 (pyridoxine) to prevent peripheral neuropathy
-*Add Steroids for TB meningitis or pericardial disease
*If known susceptible, INH/RMP/PZA x 2 months
followed by INH/RMP for 4 months
If suspect susceptible, but no susceptibility results
available, add EMB
*Usually start RIPE, then drop EMB once susceptibility
results return
Active TB - Side Effects
Isoniazid (INH) - rash3, hepatitis2, neuropathy
Rifampin (RMP) - drug interaction, rash1, hepatitis3
Pyrazinamide (PZA) - hepatitis1, rash2, arthralgia
Ethambutol (EMB) - eye toxicity, rash4
Active TB in Pregnancy
- Risk of untreated active TB to a pregnant woman and her fetus outweighs risk of adverse effects of drugs used in its treatment
- INH, RIF, EMB are considered SAFE in pregnancy, so all three should
be used as initial treatment
– Category C due to lack of controlled studies in pregnancy but lack track
records of safety in pregnancy - PZA added if extensive disease, smear-positive pulmonary disease,
disseminated TB, intolerance of other agents - Do not treat latent TB until after delivery unless high risk of TB
reactivation, and use 4R regimen
Active TB and HIV
Treatment is the same as for TB in HIV-negative patients
* ART must be adjusted for interactions with Rifamycins
– Initiation of ART in ART-Naïve Patients:
* If CD4 < 50 → within 2 weeks
* If CD4 > 50 → within 8 weeks
* Pregnancy → ASAP regardless of CD4
* If TB meningitis → defer for ~8 weeks given ↑ risk of IRIS (especially if low CD4 count
* IRIS: Increased risk if low CD4, high viral load, disseminated TB
– Pre-emptive steroids if high risk for IRIS
Steroids for TB meningitis* (similar to non-HIV patients) but not TB pericarditis
Non-tuberculous Mycobacteria- dx and tx
Over 190 species and subspecies: M avium complex, M. kansasii, M xenopi, M abscessus
Diagnostic criteria (NTM pulmonary disease): Both clinical (pulmonary or systemic sx) AND
radiologic (nodular or cavitary lesions on CXR, or CT with bronchiectasis)
Plus one of:
* 2 or more sputum positive for same species NTM
* 1 BAL/bronch culture positive for NTM
* Biopsy with mycobacterial histology (AFB/granuloma) and positive culture
Treatment: Requires discussion around clinical factors, infecting species and patient priorities.
* Ideally susceptibility-based therapy (not empiric)
* Minimum 3-drug regimen (macrolide, ethambutol, +/-rifampicin +/- aminoglycoside)
Malaria – Diagnosis
Species:
* Plasmodium falciparum
– Can be severe
– Present within 3 months
– Infects RBCs of all
stages
* P. ovale and P. vivax
– May present years later due to
hypnozoites in liver
Diagnostic Techniques:
Thick and thin blood smear x3, separated
by at least 6 hours over 24 hour period
- Thick smear: Looks for any parasite
(sensitivity 87%)
- Thin smear: Identifies parasitemia (%) and
speciation by stain
Rapid detection test (RDT)
Separate tests for P. falciparum and others;
highest Sn for P. falciparum
Malaria – Severity Criteria
Criteria for Severe Malaria:
* Essentially any end organ
dysfunction
* Neurologic = confusion, prostration
(severe weakness), seizures
* Respiratory = ARDS, pulmonary edema
* Hematologic = DIC (anemia,
thrombocytopenia, elevated LDH),
jaundice, hemoglobinuria à Black water
fever
* Severe anemia (Hgb < 50)
* Hypoglycemia (glucose < 2.2)
* Acidosis (pH < 7.25, HCO3 < 15)
* Renal impairment (Cr > 265)
* Lactic Acidosis
* Hyperparasitemia
– ≥5% for non-immune adults
– ≥10% for semi-immune adults
Malaria – Management
Uncomplicated
P. falciparum CS Chloroquine
CR (most common) Atovaquone-proguanil OR Quinine +doxycycline OR Quinine + clindamycin
Non-falciparum spp.* CS (most common) Chloroquine
CR - Atovaquone-proguanil OR
Quinine + doxycycline
Complicated
IV artesunate X 48h then PO
* Atovaquone-proguanil OR
* Doxycycline OR
* Clindamycin
- If P. vivax or P. ovale, add primaquine (check G6PD level first) to treat hypnozoite stage
- Repeat smears q6-12h to monitor parasitemia
- If artesunate not available for complicated malaria, give IV quinine as alternative
(monitor QT and for hypoglycemia)
Malaria – Chemoprophylaxis
Chloroquine/
Hydroxychloroquine
Only use in sensitive areas (e.g. Haiti, DR, central America, etc.). Weekly dosing;
start 1w prior and stop 4w post. Safe in pregnancy
Atovaquone-proguanil
(Malarone)
Daily dosing; start 1d prior and stop 7d post. Insufficient data regarding use in
pregnancy. Well-tolerated
Doxycycline Daily dosing; start 1d prior and stop 4w post. GI upset, photosensitivity.
Contraindicated in pregnancy
Mefloquine Weekly dosing; start 2-3w prior and stop 4w post. Associated with bizarre
dreams and can cause severe neuro-psychiatric symptoms (sz/psychosis); QT
prolongation. Safe in pregnancy; check to ensure no resistance in destination
Primaquine Use only if others contra-indicated. Daily dosing; start 1d prior and stop 7d post
Need to check G6PD level. Contraindicated in pregnancy/breastfeeding
Helminths (worms) 101
- Clue is eosinophilia (Helminths contained to GI tract may not have eosinophilia).
- Dx with stool/urine/sputum microscopy (ova and parasites), +/- serology
- Echinococcus (granulosus/multilocularis): Liver cysts, sometimes lung cysts.
Diagnosed with combo imaging + serology/Antigen. Staged based on imaging, tx
depends on stage but may include albendazole, aspiration, surgery or monitoring. - Schistosoma (mansoni/haematobium etc): Water/snail host, subtropical and tropical
areas, chronic infection, can cause liver/bladder CA. Dx. Tx. Praziquantel - Taenia solium(pork): Can cause taeniasis (eating infected/undercooked meat), or
neurocysticercosis (eating eggs). Tx neurocysticercosis with albendazole +/- praziquantel +/- steroids - Trichinella spiralis (trichinosis) from eating undercooked wild animal meat
(bear/pork). GI symptoms, muscle pain (cysts). Tx. Albendazole/mebendazole.
Strongyloides Stercoralis
From skin contact with soil in tropical and subtropical regions (e.g. walking on a
beach) – assume exposure in anyone living for >1 month in endemic areas
* Can cause lifelong asymptomatic infection where host continuously reinfects self
* Symptomatic infection may be eosinophilia, diarrhea, itching and respiratory
symptoms (may diagnose with O/P or serology)
* With glucocorticoids or other immunosuppression can get disseminated disease
which can cause recurrent gram-negative infections (including meningitis) and is highly fatal
* Screen exposed patients with serology prior to starting immunosuppression
* Treatment is Ivermectin (1 or 2 doses)
Candidemia
Risk Factors:
* Use of broad-spec antibiotics
* ICU admission
* CVC
* TPN
* Neutropenia
* Immunosuppressive agents (steroids, chemo,
etc.)
* Intra-abdominal surgical procedures
* Necrotizing pancreatitis
* Candida colonization x 3 sites
Management:
* Stable, no recent azole exposure → fluconazole
* Unstable, neutropenic, or recent azole exposure →
echinocandin
* Pregnancy → amphotericin B
* CNS infections amphotericin B +/- flucytosine
Remove central lines (especially if prolonged candidemia)
Treat for two weeks from first negative blood culture (if no
metastatic focus)
* Consult ophthalmology to r/o endophthalmitis
* Consider TTE or Abdo US if persistent candidemia to rule out IE
Aspergillus
ABPA/Allergic Rhinosinusitis Hyper-sensitivity response to Aspergillus allergens/precipitans
Elevated IgE, asthma, brown sputum, eosinophilia, bronchiectasis
Rx: Steroids/anti-IgE +/- itraconazole (anti-fungal controversial)
Aspergilloma Mycetoma that forms within a pre-existing cavity
Solitary lesion = Rx surgical resection +/- antifungal
Multiple lesions = Rx antifungal x 6 months
Chronic Cavitary Pulmonary
Aspergilosis (CCPA)
Pre-existing structural lung disease (most commonly COPD) - progression of above
Weight loss, worsening cough +/- hemoptysis
Rx antifungal x 6 months
Invasive aspergillosis
Opportunistic infection seen in neutropenia/cellular immunocompromise
Diagnosis using imaging (CT chest), indirect tests (galactomannan of serum and
sputum), or direct tests (fungal culture or pathology)
Rx: Voriconazole x ≥6 weeks or longer
Dimorphic/(Endemic) Fungi
Blastomyces dermatitidis
ie. Blastomycosis
- Border of Great Lakes (incl. Northern Ontario), Southeastern/central
USA, and St. Lawrence River (now sometimes seen in GTA) - Pneumonia, skin/joint infections
- Dx: Fungal cx, PCR, path, urine/serum antigen
- Rx: Itraconazole (mild to moderate), Amphotericin B (severe)
- Duration 6-12 months, or 3 months after complete resolution
Histoplasma capsulatum
ie. Histoplasmosis
- St. Lawrence, Ohio rivers
- Self-limited pneumonia, mTB mimicker
- Dx: Fungal cx, PCR, path, urine antigen
- Rx: None (mild), Itraconazole (moderate), Amphotericin B (severe)
- Duration ~12 weeks
Coccidioides spp.
ie. Coccidiodomycosis
New Mexico, Arizona, Mexico, Central America (valley fever)
* Suspect in returned traveler with pneumonia, meningitis
* Dx: Fungal cx, path, antigen; LP if symptoms
* Rx: None (asymptomatic), Itraconazole (symptomatic)
Mpox
Transmission (humans or infected animals):
– Direct Contact with infectious sores or body fluids (often during
sexual or intimate contact)
– Fomite Transmission, e.g. linens
– Respiratory secretions
– Vertical Transmission
* Droplet/Airborne Precautions
* Diagnosis: PCR (swab of lesion/fluid)
* Most Self-Resolve
– Tecovirimat if complications or high risk
* Vaccines:
– Partial protection if prior smallpox vaccine
– Imvamune for high risk individuals or as post-exposure prophylaxis
in high risk exposures
Ebola Virus
Syndrome:
– Fever, myalgias à GI symptoms,
anorexia
– Bleeding < 20%
Diagnosis:
– Viral culture, NAAT, viral antigens,
serology from appropriate sites
- Supportive care
– Essential procedures/bloodwork only
– Do not forget DDx -> MALARIA!
– Monoclonal antibody treatments
Measles Virus
Syndrome:
– fever, cough, coryza, conjunctivitis,
Koplik spots, rash (centrifugal)
* Infection Control:
– Airborne precautions, contact
tracing (4 days prior to rash, 4 days
after rash)
Diagnosis:
– PCR of pharynx/NP/urine; serology
can be false negative early
* Complications:
– Pneumonia, encephalitis, subacute
sclerosing panencephalitis (SSPE)
* Post-exposure prophylaxis:
– MMR, Measles immunoglobulin if
susceptible, based on time from
exposure
Lyme Disease Management Pearls
- Erythema Migrans: Typical Lesions are clinical diagnosis. If atypical, acute and convalescent serology
- For early disseminated and late manifestations, serology for diagnosis rather than PCR (including neuro and
arthritis) - Screen with ECG if early lyme disease and symptoms of carditis (dyspnea, edema, palpitations,
lightheadedness, chest pain, and syncope) - Indications for Admission: significant PR prolongation (PR > 300 milliseconds), other arrhythmias, or clinical
manifestations of myopericarditis - For telemetry, may require temporary pacing
- Post Treatment Lyme Disease Syndrome: persistent symptoms after treatment. Usually, non-infectious.
- Clinical signs of ongoing infection (e.g. arthritis): consider second course of tx with IV
- If ongoing arthritis after 2nd tx course: refer to rheumatology for DMARDs
- If no arthritis or objective signs of infection: recommend against further antibiotics
- Consider coinfection (Babesia, Anaplasma), especially if ongoing fevers while on antibiotics
Fever of Unknown Origin (FUO)
Classic Definition: T > 38.3C over 3 wks, with 1 wk investigations – Core features are prolonged fever without clear source despite
reasonable investigations (rather than rigid definition)
First line investigations: – History and physical exam, comprehensive fever diary – CBC + diff, blood film, lytes, Cr, LDH, TSH, CK, LFTs, SPEP
– Blood cultures (X 3 sets), urine C&S
– HIV, CMV IgM, Hepatitis serology
– CXR, abdominal U/S [or CT Chest/abdo/pelvis if available]
Infections in Immunocompromised Hosts
LTBI: TST/IGRA if >1 TB risk factor* and either TNF-a or Prednisone >15mg/d for >4
weeks (or equivalent).
– * Close contact w TB, recent immigration high risk country, high risk work/life exposure etc.
– If positive, rule out active TB and treat latent TB. (can give immunosuppression once treatment started)
* Hepatitis B: Screen w/ HBsAg (+/- coreAb) if biologic or Prednisone > 7.5mg/d – Consider need for treatment/prophylaxis
– **Rituximab is high risk for reactivation, must start prophylaxis with entecavir or Tenofovir
* Hepatitis C: Some risk of reactivation, screen with serology for TNF-a or long-term
steroids
* PJP: Consider TMP-SMX prophylaxis if Prednisone > 20mg/d for > 4-8 weeks
* Strongyloides: Screen with serology if planned immunosuppression in anyone who
lived (usually >1m) in tropic or subtropic area.
– Treatment with/ Ivermectin 200 mcg/kg PO day 1, 14
* *HIV: Although no evidence for worsening infection, individuals are usually screened
for HIV alongside Hepatitis B and C when starting immunocompromising treatment
Line Infections
Diagnosis
– Fever + Indwelling line - consider diagnosis
– Blood cultures from separate sites at same time (line and
periphery)
– If shock, removal of line and culture tip
Treatment
– Remove line if possible – ALWAYS for S. aureus, Candida spp,
complicated infection (ie. thrombophlebitis, IE, OM)
– Directed therapy x 7d (minimum 14 days if S. aureus /
Candida)
