INFECTIOUS DISEASES

Editor: Michael McHenry, MD, PhD
Faculty Reviewer: Milner Staub, MD

General Tips

Vanderbilt Antibiotics Stewardship Program (VASP) has a website (https://www.vumc.org/antimicrobial-stewardship-program/) with VUMC antibiograms, local resistance patterns
Cross reference with IDSA guidelines to ensure the most up to date care.
Does your pt need to be on precautions? Check the Infection Prevention Website (https://www.vumc.org/infectioncontrol/12177) under 'isolation' tab or page the infection control pager in E-star paging for additional questions
Page 317-4376 for approval of restricted antimicrobials at VUMC (page the VA ID fellow at the VA)
Both lab and clinicians are required by law to report diagnosis and treatment for reportable disease

Bacteremia

Author: VASP

Interpreting GenMark ePlex® Results

Background

When BCx turn positive, the lab reports Gram stain and GenMark ePlex® results to help guide empiric therapy, while awaiting further species identification and susceptibilities.

Management

Start empiric antibiotic therapy (based on clinical picture and table below)
Consider ordering repeat BCx x2 based on organism to document clearance
Repeat for: Staph (MRSA or MSSA), Staph lugdunensis
If source control & no endovascular infxn, no need to repeat (most other strep and GNR's)
VUMC antibiograms (https://www.vumc.org/antimicrobial-stewardship-program/antibiograms) can be used to reference typical resistance patterns and most common organisms in blood cultures.
Candida in a blood culture is NEVER considered a contaminant

Gram Positive Cocci

Some gram-positive cocci in blood cultures are NEVER considered a contaminant whereas other gram-positive cocci are often contaminants. See algorithm for interpreting GPC in blood cultures on VASP website.

Organism	Resistance Marker	Preliminary Recommendation
Staphylococcus aureus or Staphylococcus lugdunensis ID Consult REQUIRED	mecA detected	Start vancomycin IV
	No mecA detected	Start nafcillin or cefazolin Stop empiric vancomycin IV
Staphylococcus epidermidis -Often skin contaminant -Repeat cultures, start therapy if uncertain	mecA detected	Start vancomycin IV
	No mecA detected	Start nafcillin or cefazolin Stop empiric vancomycin IV
Other coagulase negative Staph -Often skin contaminant -Repeat cultures, start abx if uncertain		Start vancomycin IV
Streptococcus: agalactiae, pyogenes, anginosus		Start penicillin IV or CTX IV Stop empiric vancomycin
Streptococcus pneumoniae		Start ceftriaxone Stop empiric vancomycin Await PCN sensitivity data
Other Streptococcus -May be contaminant		Start ceftriaxone Stop empiric vancomycin Await PCN sensitivity data
Enterococcus faecalis ID Consult REQUIRED	vanA or vanB detected	Start daptomycin 8-10mg/kg/day IV Don't treat w vancomycin IV Contact precautions
	No vanA or vanB	Start ampicillin Stop empiric vancomycin IV
Enterococcus faecium ID Consult REQUIRED	vanA or vanB detected	Start daptomycin 8-10mg/kg/day IV Don't treat w vancomycin IV Contact precautions
	No vanA or vanB	Start vancomycin IV Follow-up ampicillin sensitivities
Micrococcus -Often if in a single blood culture is skin contaminant		Repeat BCx Start vancomycin IV if uncertain

Gram Positive Rods

Organism	Preliminary Recommendation
Listeria monocytogenes	Start ampicillin Stop empiric vancomycin IV
Other Gram positive rod (eg Bacillus cereus, Corynebacterium, Cutibacterium acnes, Lactobacillus) -Often skin contaminant -Repeat cultures, start therapy if uncertain	Start vancomycin IV Follow-up sensitivities; some GPRs are resistant to vancomycin

Gram Negative Rods

*Consult ID if carbapenem resistance detected*

Organism	Preliminary Recommendation
Acinetobacter baumannii	Start ampicillin/sulbactam
Bacteroides fragilis	Start metronidazole If polymicrobial infection, piperacillin/tazobactam, ampicillin/sulbactam, or meropenem based on other organisms Do NOT double cover anaerobes
Citrobacter spp.	Start/continue cefepime
Cronobacter sakazakii	Start/continue cefepime
Enterobacter (non-cloacae complex)	Start/continue cefepime
Enterobacter cloacae complex	Start/continue cefepime
Escherichia coli	Continue empiric coverage and await susceptibilities
Fusobacterium nucleatum Fusobacterium necrophorum	Start ampicillin/sulbactam or start/continue metronidazole
Haemophilus influenzae	Start/continue ceftriaxone
Klebsiella oxytoca	Continue empiric coverage and await susceptibilities
Klebsiella pneumoniae group	Continue empiric coverage and await susceptibilities
Morganella morganii	Start/continue cefepime
Neisseria meningitidis	Continue empiric coverage and await susceptibilities
Proteus spp. Proteus mirabilis	Continue empiric coverage and await susceptibilities
Pseudomonas aeruginosa	Start/continue cefepime or piperacillin-tazobactam
Salmonella spp	Start/continue ceftriaxone
Serratia spp. Serratia marcescens	Start/continue cefepime
Stenotrophomonas maltophilia	Start trimethoprim-sulfamethoxazole (15-20mg/kg/day divided q8h for normal renal function)

Gram-Negative Resistance Genes

Resistance Gene	Recommendation
CTX-M Positive (ESBL)	Start meropenem Consider an Infectious Diseases consult Contact precautions (see Infection Prevention website)
IMP Positive KPC Positive NDM Positive OXA (OXA-23 and OXA48) Positive VIM Positive	Carbapenemase-producing organism Obtain Infectious Disease consultation Contact precautions (see Infection Prevention website)

Central Nervous System Infection

Author: VASP

Bacterial Meningitis

Evaluation

Blood cultures prior to antibiotics if possible
Head CT pre-LP, only if: Immunocompromised, hx of CNS diseases (shunts, trauma, tumors), papilledema on exam or FND, AMS, or new onset seizure.
If there is a delay in obtaining head CT or LP, DO NOT delay antibiotics.
Lumbar puncture (See Procedures Section):
Obtain: Opening pressure, cell count + differential, glucose, protein, bacterial culture
Send an extra tube or two of CSF to the lab, if possible, to be frozen in case extra testing is needed (Order 'Miscellaneous test' and for test name put "Please freeze CSF in virology;" reference lab: VUMC, specimen type: CSF)
Additional studies to consider in select pts: HSV 1, 2 PCR (NOT antibodies), VZV PCR, VDRL, Crypto Ag, fungal and/or AFB cultures, MTB PCR, West Nile Virus Ab, Enterovirus PCR, Histoplasma Ag, or Biofire Meningitis/Encephalitis Panel. These should not be performed routinely on all pts and consult ID where management questions exist.
If Biofire Meningitis/Encephalitis Panel is performed, double check what is included to avoid sending duplicate individual tests (ie HSV, VZV, enterovirus, etc.) A negative cryptococcus on Biofire does not exclude disease (CSF Crypto Ag is more sensitive)

Management

Antibiotics as soon as possible
Ceftriaxone 2g IV q12h + Vancomycin, adjusted for renal function
Piperacillin-tazobactam cannot be used due to poor CNS penetration
IV ampicillin 2g q4h for optional coverage of Listeria for immunocompromised pts, pregnant women, or age >50 (adjust based on renal function)
IV acyclovir 10 mg/kg (based on adjusted body weight) q8h, if suspected HSV or VZV meningitis, make sure to run with adequate pre-hydration with NS
Consider empiric PO/IV doxycycline 100mg BID if tick-borne illness is suspected
Steroids: IDSA guidelines-steroids (dexamethasone 0.15 mg/kg q6h) should be given 10-20 minutes before the first dose of abx, or at the same time, in pts with suspected bacterial meningitis. IF pneumococcus is isolated, continue IV steroids for 2-4 days; otherwise, can discontinue
ID consultation: Duration should be guided by ID and varies based on organism recovered

Encephalitis

Background

The presence or absence of normal brain function/cognition is the important distinguishing clinical feature between encephalitis and meningitis

Evaluation

MRI more sensitive that CT, although imaging may or may not demonstrate abnormal radiographic findings in pts with encephalitis
LP – similar studies as for meningitis (see above) + BioFire MEP for ALL pts

Management

Acyclovir 10mg/kg IV q8hr (based on adjusted body weight), consideration of antibacterial therapy if unable to conclusively exclude a bacterial meningitis, consideration of doxycycline if tick-borne infection is on the differential, and further treatment as guided by ID
ID consult is strongly encouraged for all pts with suspected encephalitis

Brain Abscess

Evaluation/Management

Consult: Neurosurgery and ID
Blood Cultures, HIV testing in any pt with a brain lesion
Empiric antibiotics:
IV Vancomycin (dose per PK) + ceftriaxone 2g IV q12h + metronidazole 500mg IV/PO q6h
If concern for extension from otitis externa, use an antipseudomonal cephalosporin (cefepime 2g IV Q8h) instead of ceftriaxone
Brain abscesses generally polymicrobial, thus broad-spectrum antibiotics indicated
Aminoglycosides, macrolides, tetracyclines (e.g. doxycycline), clindamycin, beta-lactam/beta-lactamase combinations (e.g., Zosyn) and 1st-generation cephalosporins (e.g., cefazolin) should NOT be used as they do not cross BBB at high concentration.
Antibiotic Duration: based on surgical drainage and ID guidance

Epidural Abscess

Management

If spinal lesion, consult 'Spine surgery' and it will be directed to Ortho-Spine or Neurosurgery, depending on who is on call.
Abx should be started as soon as the diagnosis of epidural abscess is suspected, immediately following the collection of two sets of blood cultures
Vancomycin 15-20mg/kg IV q8-12h (adjusted for renal function) + ceftriaxone 2g IV q24h (or q12hr if there is secondary meningitis)
Use cefepime 2g IV q8h instead of ceftriaxone if concern for Pseudomonas
ID consult is strongly encouraged and they will guide duration

Diabetic Foot Infection

Author: VASP

Foundational Principles

Do NOT use antibiotics to treat uninfected wounds as patient harm outweighs benefit.
ALL wounds are colonized with microorganisms and superficial wound cultures should not be collected nor used to make treatment decisions.
Do NOT administer antibiotics to clinically stable patients until deep tissue or operative cultures are obtained.
Failure of oral antibiotics used for < 48 hours is NOT a reason to use broad-spectrum antibiotics.

Evaluation

Plain radiograph for all pts; MRI w/contrast if abscess/osteo suspected
Use of inflammatory markers such as ESR or CRP at baseline may help determine level of inflammation with periodic trending (e.g. weekly) thereafter. Do NOT repeat these tests daily.
BCx (prior to antibiotics) if systemic signs of infection, or severe infection
Do not culture superficial swabs of lesions, as these generally only grow colonizing organisms.
Consider obtaining MRSA nasal PCR. (ensure collected before nasal decolonization); ~90% negative predictive values for diabetic foot infections
Consult podiatry if osteomyelitis present for bone specimen culture and pathology (either from debridement specimen or bone biopsy) prior to starting antibiotics.
Consult surgery if concern for abscess, gas in tissue, joint involvement
Assess peripheral vasculature, consider arterial flow studies/vascular surgery consult

Management

Assess Severity:

Mild: local infection, skin/subcutaneous tissue only, erythema >0.5 cm but ≤2cm from ulcer
Moderate: local infection w/erythema > 2 cm from ulcer or deeper structures included without SIRS
Severe: local infection with systemic inflammation as evidenced by >2 SIRS criteria
Consider anti-pseudomonal coverage only if at risk for Pseudomonas infection (e.g. previous Pseudomonas on culture, water exposure; hospitalization within previous 90 days AND IV antibiotic use, immunocompromise).
Consider MRSA coverage with risk factors: previous MRSA on cultures, hospitalization within previous 90 days AND IV antibiotic use, IV drug use, hemodialysis
Consider anaerobic coverage with metronidazole

Treatment Regimens:

	Non-purulent, no MRSA risk factors	Purulent, MRSA risk factors	Duration
Mild	Preferred: • Cephalexin 500mg PO QID or 1g TID • Cefadroxil 1g PO BID (upon discharge only) Alternative: Amoxicillin/clavulanate 875/125mg PO BID	MRSA only with risk factors: • Doxycycline 100mg PO BID (add to β-lactam) Trimethoprim/sulfamethoxazole 5-8mg/kg/day (alone)—Preferred if severe penicillin allergy	7-14 days
Moderate	Preferred: • Ampicillin/sulbactam 3g IV Q6H • Ceftriaxone 2g IV daily ± PO metronidazole 500mg Q12H P. aeruginosa only with risk factors (change to): • Piperacillin/tazobactam 3.375g IV Q8H ext infusion • Cefepime 2g IV Q8H ± metronidazole 500mg PO Q12H • Levofloxacin 750mg PO daily ± metronidazole 500mg PO Q12H	MRSA only with risk factors (add): • Doxycycline 100mg PO BID • Trimethoprim/sulfamethoxazole 5-8mg/kg/day for SSTI and 8-12mg/kg/day for osteomyelitis • Linezolid 600mg PO BID Vancomycin (pharmacy consult)	7 – 21 days for soft tissue infection only If osteomyelitis: -24-48 hours if complete resection of infected tissue -1 – 3 weeks if only residual soft tissue infection 3 – 6 weeks if residual bone infection with resection or 4 – 6 weeks without resection
Severe	Preferred: -Ceftriaxone 2g IV daily + metronidazole 500mg PO Q12H PLUS -Vancomycin (pharmacy consult), OR -Linezolid 600mg PO BID† P. aeruginosa only with risk factors (change to): • Piperacillin/tazobactam 3.375g IV Q8H ext infusion • Cefepime 2g IV Q8H + metronidazole 500mg PO Q12H †Linezolid is preferred for use in necrotizing soft tissue infections Adjust regimen based on deep culture results		7 – 28 days for soft tissue infection only If osteomyelitis: • 48 hours if complete resection of infected tissue • 7 – 21 days if only residual soft tissue infection 21 – 42 days if residual bone infection with resection or 28 – 42 days without resection

Conversion to PO antibiotics (including osteomyelitis):

Active agent available
Functioning GI tract
Clinically stable
Select active agent(s) against recovered pathogen(s)

Additional Information

If pt HDS, hold abx until deep tissue/operative cultures obtained.
Most diabetic foot infections are polymicrobial in nature.
Culture results will help therapy, but all pathogens identified may not require treatment. Would discuss with ID if complex

Endocarditis

Author: Justin Smith

Background

Multiple etiologies of endocarditis:
Typical Bacterial
- S. aureus, Enterococcus spp (E. faecalis most commonly), viridans group streptococci, Strep gallolyticus (formerly S. bovis)
- HACEK: Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella
Other infectious
- Culture negative: often recent antimicrobial exposure, slow growing organism
- Coxiella, Brucella, Bartonella, Chlamydia, Legionella, Mycoplasma, Tropheryma whipplei, Cutibacterium acnes (formerly P. acnes)
- Fungal: Candida and aspergillus most common
Non-infectious: a.k.a., marantic endocarditis, Libman-Sacks Endocarditis
- Rare, most common in advanced malignancy, SLE, inflammatory conditions
- Higher risk for embolization compared to IE
Risk factors: IV drug use, congenital heart disease, valve abnormalities, intracardiac devices, recent cardiac surgery

Presentation

Fever (90%), murmur (85%), other: splenomegaly, splinter hemorrhages, Janeway lesions, Osler nodes, Roth spots
Persistent bacteremia despite appropriate treatment, new onset cardiac dysfunction, new onset valve abnormalities, stroke, other thromboembolic events, metastatic infections/abscesses, splenic abscess, septic pulmonary emboli

Duke Criteria:

Pathologic Criteria

Microorganisms: culture or histology proven: vegetation, embolus, or intracardiac abscess
Pathologic vegetations: vegetation of abscess with histology proven endocarditis

Clinical Criteria

Definite: 2 Major, 1 major and 3 minor, or 5 minor
Possible: 1 major and 1 minor, or 3 minor
Rejected: firm alternate diagnosis, resolution of evidence with <4 days of antibiotics, or absence of pathologic evidence with <4days of antibiotics

Major Criteria	Minor Criteria
2x positive blood cultures from a typical organism	Predisposing heart condition/IDU
Evidence of endocardial involvement	Fever
	Vascular phenomena (glomerulonephritis)
	Immunologic phenomena (Osler nodes, Roth spots, +rheumatoid factor, GN)
	Micro (cultures that don't fit the above, or serologic evidence of acute infection)

Evaluation

Physical exam: murmur, decreased peripheral perfusion, evidence of heart failure, petechiae, splinter hemorrhages, Janeway lesions/Osler nodes, organomegaly
Blood cultures: at least three sets from different sites over a span of several hours
Echo (TTE vs TEE)
It can be reasonable to start with TEE if pretest probability is high enough, if pt already has known valvular abnormalities, or TTE will be technically difficult
EKG: new heart block or prolonged PR raises concern for endocardial/perivalvular abscess. Endocarditis pts should be on telemetry, monitored closely by team.
CXR: infiltrates suggestive of septic pulmonary emboli, pulmonary edema, cardiomegaly
Imaging of distant affected site if concerned for septic emboli
Other advanced imaging in select scenario: cardiac CTA, cardiac MRI, FDG-PET/CT

Management

Empiric antibiotics:
If bacteria isolated from blood, reference bacteremia section for abx choice
If awaiting cultures
- Native valve: Vancomycin +/- GNR coverage (depending on clinical stability, risk factors, etc)
- Prosthetic valve: Vancomycin and cefepime, consider gentamicin
Antibiotic Duration: determined by ID, often 4-6 weeks
Cardiac surgery consult: if valve dysfunction, perivalvular abscess, large (>20mm) vegetations, heart block, ongoing embolization on abx, delayed Cx clearance (>1 week on abx)

Additional Information:

Complications:

Cardiac:
Heart failure: usually secondary to valve dysfunction. Most common when aortic valve involved, risk also depends on organism (worst is Staph aureus)
Perivalvular abscess: suspect when there are conduction abnormalities on EKG.
Pericarditis: can be suppurative or non-suppurative
Intracardiac Fistula
Septic emboli and metastatic abscesses
Mycotic aneurysm: usually occurs at vessel branch points

Follow Up

Repeat TTE at completion of treatment to establish new baseline
Followed for valvular dysfunction with frequency determined by nature of the dysfunction
Regular dental care; prior IE is an indication for SBE prophylaxis with dental work.
Episode of IE is an indication for PDA or VSD closure

Fever in a Return Traveler

Author: Michael Daw

Background

Treatment of fever in a return traveler will depend on where the traveler came from and what risk their fever poses to themselves or others.
ALWAYS remember to think about common US illnesses that are frequently transmitted due to exposure to crowds in airports, airplanes, bus stations, etc (mononucleosis (EBV and CMV), influenza, other common cold viruses, etc.)

Presentation

Is the pt sick? AMS, tachypneic, hypotensive
Do they have signs of severe disease? Cyanosis, meningism (nuchal rigidity, photophobia, headache), peritonitis, digital gangrene

History Pearls

Obtain travel history: location(s), activities, purpose of travel, accommodations
Did they visit a friend or relative? (less likely to seek pretravel medical advice, higher risk for malaria, typhoid fever, tuberculosis, hepatitis A, and STD)
Consumption of unclean water or risky foods, insect/tick bites, animal exposures, sexual contact
Were they hospitalized abroad? (consider MDR organisms)
Evaluate immunization status and chemoprophylaxis received before/during travel.
Check out the CDC Yellow Book: https://www.cdc.gov/yellow-book/index.html

Etiologies based on clinical syndrome:

Clinical Syndrome	Possible Etiologies
Skin rash with or without conjunctivitis and fever	measles, typhus, dengue, chikungunya (both dengue and chikungunya tend to also cause severe muscle and joint aches), Zika, meningococcemia, hemorrhagic fevers such as Ebola
Rapid respiratory rate	influenza, Middle East respiratory syndrome [MERS], pneumonic plague, histoplasmosis
Persistent cough	TB, pertussis, fungal infections like coccidioidomycosis, blastomycosis, histoplasmosis, cryptococcus
Decreased consciousness	malaria, meningococcal meningitis, rabies, tickborne encephalitis
Bruising or unusual bleeding without previous injury	hemorrhagic fevers
Persistent voluminous diarrhea	campylobacter, shigella, salmonella – although many do not usually present with fever - Traveler's diarrhea, cholera, giardiasis
Persistent vomiting other than air or motion sickness	norovirus
Jaundice	hepatitis A, B (if not vaccinated), D, E; leptospirosis
Flaccid paralysis of recent onset	polio
Genital lesions	HIV, G/C, hepatitis, syphilis, Mpox, hemorrhagic fevers, lymphogranuloma venereum

If no localizing symptoms, consider usual incubation periods:

<21 days: East African trypanosomiasis, dengue, Zika, chikungunya, Japanese encephalitis, leptospirosis, malaria, meningococcemia, nontyphoidal salmonellosis, plague, typhoid fever, typhus, viral hemorrhagic fevers, yellow fever
>21 days: acute HIV, acute systemic schistosomiasis, amebic liver abscess, borreliosis (relapsing fever), brucellosis, leishmaniasis, malaria (esp after ineffective prophylaxis), rabies, TB, viral hepatitides, West African trypanosomiasis
Relapsing fevers (fever spikes separated by days or weeks): borreliosis, malaria
48 hour interval fevers: plasmodium vivax or P ovale
72 hour fevers: Plasmodium malariae
intermittent, unsynchronized: P falciparum
Domestic travelers (within the US), consider: tickborne illness (ehrlichia, anaplasmosis, STARI, Lyme, Rocky Mtn Spotted fever), coccidiomycosis, histoplasmosis, blastomycosis, cryptococcus, tularemia, hantavirus

Evaluation:

Most common serious cause of fever from travel to certain areas is malaria falciparum: order thick and thin blood smears and note that the order is for malaria blood smear (if you order thick and thin w/o malaria order, it will not be done in an urgent manner). If negative, order repeat smears over 24-72 hrs.
Viral hemorrhagic fevers such as Ebola, Crimean–Congo hemorrhagic fever, Marburg hemorrhagic fever, and Lassa fever are highly transmissible and require immediate treatment. IF suspicious, VUMC Infection prevention should be notified IMMEDIATELY. Special precautions and protocols should be initiated to protect treating team.
Initial labs: CBC w/diff, CMP, blood cx, rapid tests for malaria and dengue, PCR testing of plasma sample (for tick borne), CXR, blood smear (thick and thin), UA with microscopy and culture. Consider O&P, head imaging or LP, or additional abdominal imaging in the right clinical context.
Don't forget the common causes of fever (could have nothing to do with pt's travel or could be routine infections seen in US)
Empiric doxycycline is a reasonable adjunct for undifferentiated non-malaria fevers
Look up current outbreaks to help guide clinical suspicion. https://www.who.int/emergencies/disease-outbreak-news

Fungal Infections

Author: Ally Glover

Evaluation

Bacterial BCx can detect candidemia but low sensitivity (50%). Fungal blood cultures also with low sensitivity.
Beta-d-glucan: note will not be elevated in mucormycosis, cryptococcosis, and blastomycosis.
Aspergillus galactomannan: BAL > serum.
Pts with risk factors for candidemia (TPN, chronic line, GI disease, persistent neutropenic fever) with concerning clinical syndrome can be treated empirically with micafungin.

Candida Infections

Background

Part of normal flora of human GI and GU tract
Broad range of associated diseases from vaginal candidiasis to candidemia
Pts at highest risk of severe / invasive candida infection (candidemia):
Burn / surgical ICU pts
Solid organ recipients
Chemo pts / malignant heme pts
TPN dependent / central access pts (especially in ICU)

Presentation

Oropharyngeal: white plaques/patches in mouth +/- erythema, painful when eating
Esophageal: dysphagia/odynophagia, chest pain w/ swallowing
Vulvovaginitis: white, thick discharge; pruritus/erythema
Balanitis: white patches on penis with severe burning/itching
Mastitis: breast feeding pts with nipple injury
Invasive focal infections
UTI: ascending infection (can often be unilateral) vs. hematologic source (micro abscesses)
Peritonitis: often in peritoneal dialysis pts
Mediastinitis: often post thoracic surgery
Hepatosplenic: often in pts who just recovered from neutropenia in setting of heme malignancy
Candidemia: sepsis, often in setting of critical illness, think about when above risk factors present

Evaluation

Blood: candida is NEVER a contaminant in blood cultures
Urine: culture is standard method of identification but RARELY a urinary pathogen

Management

Candidemia / critical illness: start micafungin 100mg daily, consult ID
Vulvovaginitis: fluconazole 150mg x1 if mild, 150mg every 72 hrs for 2-3 doses if severe
Oropharyngeal: nystatin oral suspension if mild thrush, if moderate – severe candidiasis then fluconazole 100-200mg qday for 7-14 days
Esophageal candidiasis (AIDS defining illness): fluconazole 200-400mg qday or micafungin 150mg daily for 14-21 days as an alternative agent

Additional information

Remember to check susceptibilities (C krusei has intrinsic azole resistance and C glabrata has high rates of fluconazole resistance)

Aspergillosis

Background

Most often in pts who have prolonged neutropenia, high dose steroids, or other immunosuppressive drug regimen or condition
Take thorough hx: farming, occupational exposure where pt might have inhaled conidia

Presentation

Classic pulmonary aspergillosis presentation: neutropenic pt with fever, pleuritic chest pain and hemoptysis
Tracheobronchitis: can occur in lung transplant pts

Evaluation

Aspergillus galactomannan Ag
Lung imaging if concerned for pulmonary aspergillosis
Differentiate possible vs probable vs proven (tissue) aspergillosis as it can reflect colonization without proper clinical syndrome or host

Management

Consult ID. Usually treat with voriconazole or other triazole (posaconazole, isavuconazole). Preferred over amphotericin based on clinical trials.
Fluconazole is NOT active against aspergillus

Blastomycosis

Background

Endemic in midwest, southeast, southern central US, and parts of Canada that border the Great Lakes
Mostly pulmonary manifestations, 25-40% of infections w/ extrapulmonary involvement (skin, bone, GU, and CNS presentations)

Presentation

Pulmonary symptoms common: dyspnea, cough, fever, hemoptysis, chest pain
Verrucous lesions with irregular borders
Osteolytic bone lesions
Draining sinuses

Evaluation:

Serum and urine blastomycosis Ag
Antibody testing less useful in acute disease (interpret with caution)

Management

Pulmonary blastomycosis
Mild to Moderate: itraconazole 6-12 months
Moderate to Severe: ampho followed by itraconazole for 6-12 months
Disseminated extrapulmonary blastomycosis: ampho followed by itraconazole for a year
Note: in anyone who is immunosuppressed, especially pts with AIDS, start with amphotericin
CNS blastomycosis: 4-6 weeks of ampho followed by a year of itraconazole

Histoplasmosis

Background

The most common endemic mycosis in the US. Endemic to Ohio and Mississippi river valley.
Most infections are not clinically significant / do not require treatment.
At risk for disseminated disease (HIV, transplant recipients, immunocompromised, TNF-alpha inhibitors, elderly)
Differential diagnosis: TB, malignancy, sarcoidosis, other fungal infection

Presentation

Pulmonary histo: pna w/ mediastinal or hilar LND or masses, pulmonary nodules, cavitation
Disseminated histo: fever, mediastinal LND, diffuse pulm interstitial infiltrates, HSM, liver involvement, popular rash, cytopenias, mucosal lesions, ↑ LDH, ferritin, adrenal involvement, colonic involvement.

Evaluation

Send BOTH Urine and Serum antigens. Requires attending name to order.
Antibody testing less useful in acute disease (interpret with caution)
Other diagnostics to consider: peripheral smear/buffy coat, fungal blood cultures, LDH, ferritin, BAL with cultures and cytology
Remember histo Ag has high cross reactivity with blasto Ag

Management:

Amphotericin and Itraconazole- discuss with ID, pharmacy about dosing, duration.
Pulmonary histo:
Mediastinal granuloma, fibrosis, broncholithiasis: usually no tx.
Mild-moderate acute pulmonary histo: itraconazole if persistent symptoms > 1mo
Chronic cavitations: itraconazole, likely 1 to 2 years
Severe acute pulmonary histo: amphotericin for 1-2 weeks +/- methylprednisolone followed by itraconazole for 12 weeks
Disseminated histo:
Mild-moderate disseminated disease: itraconazole for ~12 months
Severe disseminated disease: ampho for 1-2 weeks followed by itraconazole for ~12 mo

Additional information

Disseminated histoplasmosis can be associated with secondary HLH. Follow CBC closely.
If concerned for sarcoidosis, need to rule out histo prior to starting treatment for sarcoidosis
Urine antigen can be used to trend response to treatment

Genitourinary Infection

Author: VASP

Asymptomatic Bacteriuria

Background

Isolation of bacteria in an appropriately collected urine specimen from an individual without symptoms or signs of urinary tract infection. Bacteriuria, foul odor, urine appearance, pyuria, falls and/or confusion alone are not indicative of infection.
Oliguric ESRD pts may have bacteriuria from colonization due to lack of flushing of bladder; avoid sending UA/UCx unless pt is symptomatic
Treatment only required for specific populations:
Pregnant women (screening performed at 12 – 16 weeks)
Anticipated urologic intervention - when requesting, be sure to ask for Micro help in identifying potential pathogens needing treatment vs. likely contaminants
Some renal transplant recipients, depending on time since transplant

Complicated UTI and Pyelonephritis

See UTI algorithm (https://www.vumc.org/antimicrobial-stewardship-program/guidelines) on VASP website

Background

Fever, pyuria, and costovertebral angle tenderness suggest pyelonephritis.
Consider it a complicated UTI if any of the following are present:
Renal calculi or other obstructive disease, immunosuppressed host, abnormal urological anatomy or physiology (including stents), presence of a urinary catheter
Male sex alone does NOT qualify as complicated
Sepsis or bacteremia

Evaluation

UA with reflex urine culture ONLY in patients with symptoms
If unable to obtain history, evaluate for objective signs of infection (fever, hypotension, tachycardia, leukocytosis, etc.) and evaluate for alternative explanations (O2 requirement suggest pneumonia, post-op fever within 48 hours, etc.)
BCx and UCx prior to abx
If there is no pyuria, consider an alternative diagnosis, or proximal ureteral obstruction
Pyuria is common in the presence of a urinary catheter, kidney stones, urostomy, ileal conduit and other invasive devices, and may not indicate infection

Management

Antibiotic Duration: 7-14 days, depending on antibiotic choice
Tailor therapy once/if cultures are available. If no improvement in 48h, consider imaging to rule out complications (e.g., perinephric abscess)
Transition from IV to PO should be considered for patients who meet the following criteria: able to tolerate enteral medications, signs of clinical improvement (defervesced, afebrile, down-trending WBC, etc.)
Days of IV therapy count towards overall treatment duration.

	First Line	Alternative
Outpt	Amoxicillin-clavulanic acid 875-125mg BID x14 days	Ciprofloxacin 500mg BID or levofloxacin 750 mg daily x 7 days TMP/SMX 1-2 DS BID x 7 days
Inpt	Ceftriaxone 2g q24h Cefepime 2g q8h Pip/tazo 3.375g q8h ext infusion Meropenem 1g q8h (if h/o or confirmed ESBL within the last 90 days)	Ertapenem 1g q24 instead of Meropenem if no Pseudomonas Ciprofloxacin 750mg PO BID (500 mg PO BID if bacteremia ruled out) OR 400mg IV BID (if susceptibility confirmed) FQ's have same bioavailability if given PO or IV so oral is preferred

Uncomplicated Urinary Tract Infection (UTI)

Background

Clinical symptoms of UTI (dysuria/urgency/frequency/ hematuria) in non-pregnant, immunocompetent, neurologically intact pt with normal urologic anatomy and no indwelling urinary catheters

Management

Empiric therapy
Nitrofurantoin monohydrate: 100 mg PO BID x 5 days (avoid if any concern for pyelonephritis or if creatinine clearance <30)
Cephalexin 250-500mg q6h x5-7 days
Alternative therapies
Fosfomycin: 3 grams of powder mixed in water as a single PO dose (avoid if any concern for ascending UTI or pyelonephritis). Susceptibility test results must be requested, only possible for E. coli and E. Faecalis.
Amoxicillin-clavulanate: 875-125mg PO BID x5-7 days
Ciprofloxacin: 250mg PO BID x3 days
FQ's should be reserved for more serious infections than uncomplicated cystitis, and only after susceptibility results are confirmed given high rates of resistance
- Adverse effect profile >> beta-lactams (i.e. QT-prolongation, tendinopathies)
Avoid amoxicillin, ampicillin, and trimethoprim-sulfamethoxazole (TMP-SMX) due to increasing resistance unless culture data with confirmed susceptibility

Additional Information

MDR cystitis: ESBL isolates are increasingly common due to antibiotic overuse
Before treating, decide if this is a TRUE UTI
If true, consider Fosfomycin (if E. coli) or nitrofurantoin (if susceptibility is confirmed – K. pneumoniae and Enterobacter spp are usually resistant), gentamicin or tobramycin 5 mg/kg IV once (even in setting of AKI), or ID consultation
Ask the lab to check susceptibility results to these antibiotics for future reference

Catheter Associated Urinary Tract Infection (CAUTI)

Background

Culture growth of > 10³ cfu/mL of uropathogenic bacteria + signs or symptoms consistent with infection (without another identified etiology) + indwelling urethral/suprapubic catheter or intermittent catheterization.
This includes pts with catheters in place during the preceding 48 hours
Duration = greatest risk factor (increases 3-10% per day of catheterization)
Other risks: female sex, diabetes, elderly, colonization of catheter bag, poor care
Bacteriuria, foul odor, pyuria, urine appearance falls and/or confusion alone are not indicative of infection in pts who are otherwise asymptomatic.
Ensure clean sample collected
Ideally, catheter is removed and midstream sample obtained
If catheterization required; removal of old catheter and sample taken from new catheter

Management

Distinguish uncomplicated vs complicated UTI (see above)
Antimicrobial management:
Guided by cultures and susceptibilities
Duration: 7 – 14 days depending on abx, clinical response and whether infection constitutes complicated vs uncomplicated UTI
Special note regarding Candida UTI management: Candida is generally not pathogenic
- Presence in urine does not indicate infection (unless perinephric abscess, renal transplant, or complex fistulous disease)
- Fluconazole achieves excellent urinary penetration while micafungin does not
- If fluconazole-resistant Candida is cultured or suspected, consult ID
- Susceptibilities are not routinely run-on Candida from urine cultures and would need to be requested if concern for true infection.
Catheter management
At the least, catheters should be replaced at the time of antibiotic initiation (preferably removed).
If catheterization is necessary, intermittent catheterization is preferred over continuous use with pt educations on cleaning/hygiene prior to catheterization. Condom catheters and pure wicks also preferred over foley catheter.

GI Infections

Authors: Lin Cao, Ahmed Samy

Acute Diarrhea

Presentation

≥3 BMs/day or abnormally loose stools
Vast majority of infectious diarrhea cases are acute with more persistent diarrhea, consider additional workup for noninfectious etiologies as well
Can be watery or inflammatory (bloody stools, signs of sepsis, severe abdominal pain)
History: food hx (particularly undercooked meats or unpasteurized dairy), occupational exposures, recent travel, pet and animal exposures, immunocompromised

Evaluation

Exam: volume status, abdominal pain
Labs: CBC for leukocytosis/eosinophilia, BMP for electrolyte abnormalities, BCx if c/f systemic illness, consider GIPP or stool testing if severe illness or immunocompromise

Management

Most cases are self-limited and resolve with just supportive care
Antimotility agents: bismuth subsalicylate, loperamide
Avoid antimotility agents with C. diff and inflammatory diarrhea
Avoid abx with Shigella and EHEC (can precipitate HUS), Salmonella (prolongs carrier time)
Antibiotics only indicated with severe illness or certain immunocompromised hosts:
Cipro 500mg bid
Levofloxacin 500mg qd 3-5 days
Azithro 500mg qd 3 days

C. Diff (see GI section)

Other GI Infections:

Less commonly infectious than acute diarrheal illnesses

Whipple disease (T. whipplei):

Constellation of arthralgias (can be the first symptom to appear), weight loss, chronic intermittent diarrhea, abdominal pain
Dx: upper endoscopy with biopsy with PAS and PCR testing for T. whipplei, can sometimes also do testing from synovial fluid/lymph nodes/etc
Tx: CTX 2g IV daily or PCN 2 MU IV q4h x 2 wks followed by Bactrim 1 DS tablet bid x 1 yr

Small intestinal bacterial overgrowth (SIBO):

Presents with bloating, abdominal discomfort, watery diarrhea
More commonly seen in pts with intestinal motility disorders, chronic pancreatitis, post-surgical changes (adhesions/strictures/blind loops)
Immunocompromised pts: consider CMV, MAC, TB, fungal etiologies, cryptosporidium
Tx: Rifaximin 1650mg qdaily for 14 days

H. pylori (see GI section)

Acute cholangitis (see GI section):

Viral Hepatitis (A-E):

Also consider HSV (especially in pregnancy), VZV, EBV, CMV though less common and usually seen more in immunocompromised pts

Evaluation

HAV, HBV, HCV IgG with PCR, HDV, HEV, EBV Qt, CMV Qt, HSV Qt, VZV IgM/IgG
LFTs: elevated AST/ALT (ALT>AST generally) that often precedes elevation of bilirubin
Can present on a spectrum of severity ranging from elevated LFTs to acute liver failure; get hepatology involved early for evaluation and monitoring

Hepatitis A

Presentation: self-limited, N/V, fever, malaise, abdominal pain, jaundice, dark urine
Transmission: Fecal oral transmission
Tx: supportive care, vaccine available

Hepatitis B

Transmission: perinatal, sexual contact, parenteral

Acute:

Presentation: Most pts have subclinical hepatitis but can present with serum sickness-like syndrome, anorexia, nausea, jaundice, RUQ pain, elevated LFTs
Tx: Generally supportive care unless severe illness, then generally treat with tenofovir/entecavir
HBV is less likely to become chronic than HCV

Chronic:

Presentation: Generally asymptomatic but can progress to cirrhosis and HCC
Extrahepatic manifestations 2/2 circulating immune complexes: polyarteritis nodosa, membranous nephropathy, aplastic anemia
Tx: entecavir/tenofovir, involve GI/ID, based on development of cirrhosis, ALT, HBV DNA level, immunosuppressed status.
Vaccine available

Hepatitis C

Transmission: parenteral, blood transfusion (prior to 1992), sexual, perinatal transmission
USPSTF recommends screening in all adults 18-79

Acute Presentation

Generally asymptomatic but may have jaundice, nausea, dark urine, RUQ pain, elevated LFTs
Majority of hep C cases progress to chronic infection

Chronic Presentation:

Nonspecific nausea, diarrhea, abdominal pain, anorexia, weakness but can progress to cirrhosis and HCC, LFTs not always elevated
Extrahepatic manifestations directly related to viral infection: essential mixed cryoglobulinemia, membranoproliferative glomerulonephritis, thyroiditis, porphyria cutanea tarda, lichen planus, etc.
Tx: antivirals targeted to HCV genotype, however, there are pangenotypic regimens. Recheck viral load after 12 wks

Hepatitis D

Requires HBV for infection, consider screening with HBV

Hepatitis E

Presentation: self-limited acute infection with jaundice, malaise, anorexia, N/V, ab pain
Transmission: Fecal oral transmission
Significantly higher mortality in pregnant individuals

HIV/AIDS and ART

Authors: Kathryn Snyder and Quinton Taylor

Background

New HIV Diagnosis

ID consult if pt is not on Rogers ID service (important for initiation, follow up [CCC], social work assistance)
ART is indicated for all HIV+ pts, regardless of CD4; however, starting ART requires appropriate outpt follow up
Lab evaluation
HIV viral load and genotype
T cell subsets (CD4 Count), CBC with differential, CMP, UA
HLA*B5701 testing before using abacavir containing regimen
QuantiFERON Gold
Pregnancy testing
Viral hepatitis serologies
Toxoplasma serologies
CMP, CBC with differential, urinalysis
Other STI screening (Syphilis, Gonorrhea/Chlamydia)

Timing of ART initiation

Factors affecting timing of initiation
Drug toxicity and interactions, risks for resistance, adherence barriers
Treatment of opportunistic infections may delay initiation of ART given associated risk of immune reconstitution inflammatory syndrome (IRIS)
Delay ART for several weeks after initiation of therapy for cryptococcal meningitis, tuberculosis, and CMV retinitis
IRIS is a collection of inflammatory disorders associated with paradoxical worsening of preexisting infectious processes following the initiation of antiretroviral therapy (ART) in HIV-infected individuals. Symptoms are associated with underlying disease.

ART plan for overnight admits:

okay to continue home ART, special consideration for:
Pts with hepatic or renal dysfunction may need dose adjustment
Interactions with other newly initiated medications
If there is concern for non-adherence, can hold morning dose
Combination pills may need to be ordered as separate components
Close attention to medication reconciliation to ensure the pt's complete ART regimen is ordered

Common key regimens for initiation

Most regimens consist of an NRTI backbone (2 agents) plus a 3rd agent
Some dual therapy regimens (such as Dovato®) are non-inferior to standard 3-drug therapy
Many pts are started on combination pill regimens, including Integrase Inhibitor based regimens: Biktarvy®, Dovato®, Triumeq®, Genvoya®, dolutegravir + Descovy®

AIDS Defining Clinical Conditions

Author: Rebecca Choudhury

AIDS is defined by HIV infection with concurrent absolute CD4 count <200, CD4 percentage <14%, or one of the following conditions (predominately opportunistic infections and HIV associated malignancies):

Neurologic/Ophthalmologic

CNS toxoplasmosis

Presentation: Variable, depending on disease burden/location, may include AMS, headache, seizure, ataxia, and focal neurologic deficits, +/- fever and flu-like symptoms
Evaluation: MRI w/ring-enhancing lesions on brain imaging, serum Toxoplasma IgG/IgM and (ideally) CSF Toxoplasma PCR (though CSF Toxoplasma PCR has a low sensitivity). Response to empiric therapy (~90% will have radiographic improvement after 14 days) can also be diagnostic. Brain biopsy may be indicated if diagnostic uncertainty.
Management: Pyrimethamine, sulfadiazine, and leucovorin is the preferred regimen, discuss dosing with pharmacy. Alternative regimens: clindamycin + pyrimethamine + leucovorin, Bactrim, atovaquone + pyrimethamine + leucovorin

Progressive multifocal leukoencephalopathy (PML)

Presentation: chronic (weeks to months), progressive neurologic dysfunction, particularly incoordination and other motor dysfunction, aphasia, sometimes cognitive impairment and personality changes
Evaluation: MRI brain w/patchy areas of demyelination in the subcortical white matter; location is variable, but parietal, occipital, and cerebellar involvement are common. JC virus PCR from CSF. Brain biopsy.
Management: Initiation of ART (there is no specific JC virus-directed therapy), IRIS may occur in which case clinical worsening before improvement may be seen. Fatal if HIV goes untreated.

Presentation: Similar to other progressive dementias, with short term memory loss followed by worsening global cognitive dysfunction, motor deficits, sometimes seizures in late stages
Evaluation: MRI w/diffuse cerebral atrophy and/or demyelinating lesions similar to PML. CSF w/elevated protein +/- lymphocytic pleocytosis, with no alternative cause. Send HIV RNA from the CSF, usually + in HIV encephalopathy

Cryptococcal meningitis

Presentation: Subacute to chronically worsening HA and fevers; meningismus and photophobia may be present but are often absent; rarely, focal neurologic deficits
Evaluation: LP to check opening pressure and can send serum and CSF Cryptococcus Ag, CSF culture. Brain imaging may be non-diagnostic
Treatment: Induction therapy with amphotericin and flucytosine x14 days (at least), with repeat LP close to end of induction to confirm CSF inflammation is improving and culture is negative (note: Cryptococcus grows well on standard bacterial culture media). Following sterilization of CSF, consolidation therapy consists of high dose fluconazole for at least 8 weeks, followed by maintenance therapy with fluconazole for one year. Pts may require serial LP or VP shunt to manage ICP.
Delay ART for several weeks after start of treatment to avoid risk of IRIS.

CMV retinitis (with vision loss)

Presentation: Blurry vision, focal blind spots, visual field deficits, or scotomas and floaters. Typically begins unilateral, though often progresses to bilateral involvement.
Evaluation: Always consult ophtho if you suspect it! May cause complete retinal detachment. Check serum CMV PCR (or vitreous if able)
Management: IV ganciclovir or PO valgancyclovir (+intravitreous ganciclovir or foscarnet in severe disease). If not on ART, must delay ART for at least 2 weeks after start of CMV retinitis treatment to prevent immune recovery uveitis

Pulmonary

Pneumocystis jirovecii pneumonia (PJP)

Presentation: fever, shortness of breath, cough (usually non-productive), sometimes night sweats and weight loss. Hypoxia out of proportion to exam.
Evaluation: CT chest appearance usually bilateral and diffuse with GGOs and cystic lesions of varying size. Large cysts can rupture, causing pneumothorax.
Transbronchial biopsy, BAL, or induced sputum with cytology and GMS stain.
Sputum Pneumocystis PCR can be done, but this is a send-out with long turn-around-time
Consider serum LDH and 1,3-BD-glucan: should be elevated, but are nonspecific.
Management: Bactrim is the preferred treatment; PO is preferable as Bactrim is 100% bioavailable. Check ABG on ROOM AIR to consider of adding adjunctive steroids (If A-a gradient >/=35 mmHg and/or PaO2 <70 mmHg). Alternative regimens may include primaquine + clindamycin or IV (NOT inhaled) pentamidine.

Pulmonary tuberculosis

Presentation: With low CD4, can have upper lobe cavities but also atypical radiographic pattern, including a normal-appearing CXR. Have a high degree of suspicion in any pt with advanced HIV and respiratory complaints.
Evaluation: TB skin tests and IGRAs have a high false negative rate in advanced HIV. At VUMC, any pt with HIV and respiratory complaints must be placed on airborne until TB ruleout- 3 sputum mycobacterial smears/cultures collected at least 8 hours apart (or 2 smears/cultures with 1 GeneXpert) . If concentrated smear is negative x3, TB is unlikely (though have to follow up final culture to be sure).
Management: RIPE therapy is the standard initial treatment, with adjustment if needed for drug resistance or contraindications

Herpes simplex tracheobronchitis and/or pneumonitis/pneumonia

Evaluation: bronchoscopy with positive HSV PCR from BAL +/- lung biopsy. (Usually associated with HSV-1)
Management: agent and duration not well defined for bronchopulmonary disease; depending on severity of presentation, likely IV acyclovir to start followed by transition to PO antiviral once evidence of clinical improvement, for a total of 10-14 days.

Gastrointestinal

Esophageal candidiasis

Presentation: Dysphagia, odynophagia or both. Concurrent oropharyngeal candidiasis ("thrush') is common but not universal.
Evaluation: Typically presumptive. Treatment is the test; start fluconazole and consider EGD if symptoms do not improve after several days (in which case candidiasis may be severe, or it might not be the cause)
Management: Fluconazole; nystatin is ineffective, especially in the severely immunocompromised

Herpes simplex esophagitis

Evaluation: EGD shows diffuse ulcerations throughout the esophagus; in severe disease ulcers may coalesce into dark patches, "black esophagus." Esophageal biopsy is definitive, but can infer based on EGD appearance and serum studies.

Management:

Similar to other mucocutaneous infections, consider IV acyclovir at first and transition to PO once clinically improved

CMV esophagitis/enteritis/colitis

Presentation: GI bleeding (colitis) or dysphagia and odynophagia (esophagitis)
Evaluation: serum CMV PCR, consult GI for consideration of EGD/colonoscopy
Management: (val)ganciclovir, foscarnet if ganciclovir resistance or contraindication

Chronic (>1 mo) intestinal isosporiasis

Evaluation: Stool ova/parasite can capture Iospora belli (new name Cystoisospora belli), may need serial analysis due to intermittent shedding. Oocysts may also be seen on duodenal biopsy.
Management: Bactrim; pyrimethamine + leucovorin if Bactrim is contraindicated

Chronic intestinal cryptosporidiosis

Presentation: Diarrhea; may infect respiratory tract, causing nonproductive cough
Evaluation: on GiPP or Cryptosporidium Ag
Management: Early initiation or optimization of ART; Monotherapy with nitazoxanide is preferred; raising CD4 count >100 is necessary to cure infection

Recurrent Salmonella septicemia

Generally sensitive to fluoroquinolones, but if not clinically improving as expected you can request sensitivities from the microbiology lab.

Neoplastic

Non-Hodgkin's lymphoma

DLBCL, Burkitt's, immunoblastic (subset of DLBCL), primary effusion lymphoma, and 1º CNS

Kaposi's sarcoma

Presentation: Distinctive mucocutaneous lesions, usually raised, papular, violaceous or darkly colored, non-tender and non-pruritic. Can also involve the visceral organs (esp lungs and GI tract) and deep lymphatic system.
Evaluation: clinical, tissue biopsy for staging, HHV-8 serum PCR.
Management: Limited mucocutaneous disease may resolve with initiation/optimization of ART, but widespread or resistant disease may require additional local therapies (eg: radiation) or systemic chemo
Bacillary angiomatosis (caused by Bartonella) may present similarly, but can be distinguished from KS on biopsy. It is neither a cancer nor an AIDS defining clinical condition, and is usually treated with doxycycline.

Cervical cancer

Presentation, diagnosis, and treatment are essentially the same as in HIV-negative pts, but incidence is higher and disease progression is often more rapid

Multisystem/Miscellaneous

Extrapulmonary or disseminated Mycobacterial infection (TB and non-TB)

TB can go everywhere; some notable extrapulmonary sites include lymph nodes (e.g., scrofula), bones and joints (e.g., Pott's disease of the spine), pleura and pericardium, GU tract, and CNS. Dx can come from tissue culture and sometimes MTB PCR for more rapid detection (needs ID approval).
TB-IRIS may be severe (esp with high infection burden) and hard to distinguish from TB treatment failure; can also be seen in adequately treated TB (provoked by the presence of dead bacteria) and undiagnosed latent TB.
Disseminated MAC is usually diagnosed with AFB blood culture (only 1 positive needed). Think about it in pts with uncontrolled HIV and severe immunosuppression (esp CD4 <50), with unintentional weight loss, chronic diarrhea and/or dyspnea, and evidence of GI malabsorption or with bone marrow suppression

Extrapulmonary or disseminated Histoplasmosis, Cryptococcocosis, and Coccidiodomycosis

Can be difficult to distinguish based on clinical presentation and imaging alone. Diagnosed by culture and/or antigen testing depending on the organism and site of infection, and diagnosis may be supported by serologic studies.
Initial treatment of choice: liposomal amphotericin B in almost all cases

Chronic mucocutaneous HSV

Defined as mucocutaneous lesions present for >1 month, can be present at any site

Multicentric Castleman's Disease

See "Plasma Cell Dyscrasias" section in Hematology/Oncology for more details

Overview of Antiretroviral Therapy

Author: Kathryn Snyder and Quinton Taylor

Fixed Dose Combination Regimens

Regimen	Components	Renal Dosing	Specific Considerations
Biktarvy®	Bictegravir/ Emtricitabine/ Tenofovir (Alafenamide)	Discontinue if CrCl < 30; ok w/HD	↑ Metformin levels Contraindicated with: rifampin, dofetilide, rifabutin Avoid close admin. with: laxatives, sucralfate, polyvalent cations (iron, calcium, etc.)
Dovato®	Doltegravir/ Lamivudine	CrCl 30-50: monitor for hematologic toxicities with lamivudine CrCl<30: do not use combo pill; dose-adjust individual components	↑ Metformin levels Dose adjustment needed w/ rifampin use Contraindicated w/dofetilide and multiple antiepileptic drugs Avoid close admin. with polyvalent cations (iron, calcium, etc.) Test all pts for HBV prior to initiation
Symtuza®	Tenofavir alafenamide/ Emtricitabin/ Darunavir/ Cobistat	Discontinue if CrCl<30; ok w/HD but dose after HD on dialysis days	Contraindicated w/rifampin, rifabutin, simvastatin, multiple antiepileptic drugs Note that cobicistat can increase serum creatinine without affecting glomerular filtration so cautiously interpret serum creatinine levels
Triumeq®	Abacavir/ Dolutegravir/ Lamivudine	CrCL 30-50: monitor for hematologic toxicities with lamivudine CrCl< 30; do not use combo pill; dose-adjust individual components	↑ Metformin levels Dose adjustment needed with rifampin use Contraindicated w/dofetilide and multiple antiepileptic drugs Avoid close admin. with polyvalent cations (iron, calcium, etc.) Test all pts for HBV prior to initiation
Genvoya®	Elvitegravir/ Cobicistat/ Emtricitabin/ Tenofovir (Alafenamide)	Discontinue if CrCl < 30; ok w/HD	Many drug-drug interactions due to CYP 3A4 inhibition with cobicistat

Nucleoside RTI

Drug	Dose adj	Specific Side Effects	Major DDI	Special Points
Abacavir (ABC)	Hepatic dysfunction	↑ LDL/TG ↑ risk MI	Tenofovir	Requires testing for HLA B5701
Emtricitabine (FTC)	Renal	Rash, insomnia, rhabdomyolysis, hyperpigmentation in palms/soles	Lamivudine	Active against HBV
Lamivudine (3TC)	Renal	Nausea, HA, peripheral neuropathy, neutropenia, rash	Emtricitabine	Active against HBV
Tenofovir Alafenamide (TAF)	Discontinue if CrCl < 15	↑ lipids	AED's may ↓ levels	Tx of choice for HBV
Tenofovir Disoproxil (TDF)	Renal	N/V, ↑ LFTs, asymptomatic ↑CK, renal dysfunction, bone mineral density loss	--	Active against HBV

NRTI Additional Information

Tenofovir alone is indicated for HBV, in which case you should be mindful of renal clearance when dosing. In HIV, it is only used in combination with emtricitabine and third agent. Contraindicated if CrCl<30
Class-wide side effect: Lactic acidosis, steatosis and lipoatrophy (though very rare with contemporary NRTIs)
Resistance: M184V confers high resistance to emtricitabine and lamivudine, mid-level resistance to abacavir, hypersusceptibility to tenofovir

Integrase Inhibitor

Drug	Dose Adj.	Specific Side Effects	Major DDI	Special Points
Raltegravir (RAL)	--	--	Rifampin, AED's	--
Dolutegravir (DTG)	see special points	Hyperglycemia Weight gain	Rifampin, Efavirenz ↑Metformin	Avoid close admin with laxatives, sucralfate, iron, calcium May ↑Cr, without effect on renal function

NNRTIs

Drug	Hepatic Adj	Specific Side Effects	Major DDI	Special Points
Efavirenz	Stop if Child Pugh B/C	Psychosis, vivid dreams, SI, mania, seizures; ↑ Lipids & glucose	Azoles, antifungals, clopidogrel, some statins, clarithromycin, Buprenorphine	Give before meals; discontinue if rash develops
Etravirine (ETR)		Hypersensitivity ↑ Lipids & glucose	Clopidogrel, clarithromycin
Nevirapine (NVP)	Stop if Child Pugh B/C	Steven Johnson Syndrome	Azoles, OCP's, statins, clarithromycin	Don't start if CD4 >250 in women, CD4 >400 in men; Don't admin with antacids
Rilpivirine (RPV)	None		AED's, PPI's, dexamethasone	Must be taken with full meal; Don't use if HIV RNA >100k + CD4 < 200; Don't admin with antacids

NNRTI Additional Information

Class-wide side effect: hepatitis, rashes
Resistance: K103N resistance to efavirenz and nevirapine

Protease inhibitors

Drug	Hepatic Dose adj	Specific Side Effects	Major DDI	Special Points
Atazanavir (ATV)	Based on Childs Pugh	Jaundice, Kidney stones, AV block, Pancreatitis, Rhabdomyolysis	CYP3A4 Inhibitors PPI and H2 blockers	Admin with meals
Darunavir (DRV)		Rashes Pancreatitis	CYP3A4 Inhibitors Azoles can be used cautiously with drug level monitoring	Must stop if rash
Lopinavir (LPV)		AV block, QT changes Pancreatitis Hepatitis	CYP3A4 Inhibitors	Admin with meals

Protease Inhibitor Additional Information

All protease inhibitors must be boosted:
Ritonavir: can cause MSK pain, rhabdomyolysis, although not expected at usual doses
Cobicistat: may increase Cr without effect on renal function
Class-wide side effects: hepatitis, hypersensitivity reactions, increased cholesterol/TG, hyperglycemia, GI upset, lipodystrophy

Antimicrobial Prophylaxis per CD4 Counts

Author: Rachael Pellegrino

CD4 counts	Opportunistic Infection	Indication for Prophylaxis	Medication	Special Notes
<200 cells/mm³	Pneumocystis Pneumonia (PJP)	CD4 < 200, or CD4 < 14%, may consider discontinuation if CD4 100-200 in setting of viral suppression	TMP-SMX: 1 DS daily (qd), or TMP-SMX: 1SS qd TMP-SMX: 1 DS TIW If intolerant of TMP-SMX: dapsone*, or inhaled pentamidine, or atovaquone
<200 cells/mm³	Toxoplasma gondii encephalitis	Toxoplasma IgG + and CD4 < 100	TMP-SMX 1 DS tab daily Alternative regimens: dapsone + pyramethamine + leucovorin, or atovaquone (all regimens also effective for PJP)
<50 cells/mm³	Mycobacterium avium-intracellulare (MAC, MAI)	Only if not on fully suppressive ART and active disseminated MAC is ruled out	Azithromycin 1200 mg weekly, or Clarithromycin 500 mg BID, or Rifabutin 300 mg daily	NOT indicated for those initiating ART

Additional Screening and Prevention

Infection	Screening Indication	Prevention or Intervention
Hepatitis A Virus (HAV)	Non-immune with ↑ risk for HAV infection (MSM, IVDU) or chronic liver disease	HAV vaccine series
Hepatitis B Virus (HBV)	Pts without chronic HBV or non-immune	HBV vaccine series
Human Papilloma virus (HPV)	Age 13-45	HPV vaccine series
Influenza A and B Virus	All pts	Yearly inactivated influenza vaccine
Latent Mycobacterium tuberculosis infection (LTBI)	Pts with positive screening test for LTBI with no evidence of active disease. Pts with known exposure	(INH 300mg + pyridoxine 25-50mg) PO daily for 9 months
Streptococcus pneumoniae	All pts	Pts without any previous pneumococcal vaccines: Give PCV15 or PCV20. If PCV15 is used, also give PPSV23 in 1 year. Pts who have already received PPSV23: Give PCV15 or PCV20 one year after most recent PPSV23 vaccine Pts who have already received PCV13: Give PPSV23
Syphilis	All sexually active pts	Screening for syphilis and gonorrhea/chlamydia with treatment if indicated.
Herpes zoster (shingles)	Pts > age 50	Shingrix (recombinant zoster) vaccine series

Immune Reconstitution Inflammatory Syndrome (IRIS)

Author: Hannah Angle

Background:

An inflammatory syndrome characterized by the worsening of a pre-existing infection in patients with HIV after antiretroviral therapy (ART) initiation
Typically develops between 1 week to a couple months after starting ART
Patients with lower CD4 counts and higher viral loads who respond well to ART are at higher risk of IRIS

Evaluation:

IRIS is a clinical diagnosis
Presentation consistent with either a systemic or localized inflammatory response (specific clinical features dependent on underlying infection)
Most often seen in patients with significantly decreased CD4 counts who have a profound virologic and immunologic response to ART
Infections most associated with IRIS include CMV, PJP, HSV, HBV, HHV-8, Cryptococcus neoformans, Mycobacterium tuberculosis, and Mycobacterium avium complex (MAC)
Need to rule out drug-resistant infection or nonadherence to antimicrobials, bacterial superinfection, or medication adverse effect

Management:

Prior to ART initiation, must evaluate for all opportunistic infections (OI), especially when an inflammatory response could cause swelling in an enclosed space (cryptococcal meningitis/encephalitis, tuberculous meningitis, CMV retinitis)
If these serious CNS infections are identified, initiation of ART is often delayed until OI is well-controlled with antimicrobials
IRIS is usually a self-limited syndrome as long as infection is adequately treated
Patients with IRIS should continue both ART and antimicrobial treatment for underlying OI
In severe cases, glucocorticoids can be used to decrease inflammation

Joint Infection and Osteomyelitis

Author: Ally Glover

Background:

If high concern for septic arthritis, engage Ortho before ID. Needs arthrocentesis +/- wash out.
ESR/CRP are helpful but nonspecific in diagnosing bone/joint infections

Presentation

Septic arthritis: erythema, effusion, limited ROM and pain with passive and active ROM
Osteomyelitis: often underlying a wound (diabetic foot ulcer, sacral decubitus ulcer) but may be hematogenous as well; probe to bone positivity is diagnostic for osteomyelitis

Evaluation

CBC (leukocytosis), ESR, CRP
Blood cultures
Imaging: start with X-ray → if radiograph is negative for osteo, cannot rule out, need to get MRI. Very helpful if it's picked up on X-ray though due to specificity
Fluid studies & gram stain results from synovial fluid if concerned for septic arthritis: usually WBC > 20,000 cells/ microL

Management

If pt is sick, don't wait for culture data to start empiric antibiotics
Gram positives: empiric coverage with vancomycin until ID and sensitivities; MRSA nares being negative does not rule out MRSA skin/soft tissue infection
Gram negatives: empiric coverage with ceftriaxone or cefepime if concerned for Pseudomonas.
If concern for septic arthritis, consult Ortho, hold AC
If a pt has a foot wound with underlying osteomyelitis, talk to Podiatry/Ortho for deep tissue biopsy. If clinically stable, hold abx.
IR and CT/US guided procedures don't really do bone biopsies, so talk to surgical specialty first
Osteomyelitis abx duration: usually 6 weeks, but can do PO antibiotics based on susceptibilities, ID follow up
Septic arthritis abx duration: usually 3-4 weeks

Additional information:

Septic arthritis mimic: gout / CPPD → obtain crystal analysis with synovial studies
Less common causes of septic arthritis: gonococcal, Lyme disease (order serologies if suspicion is high)

Odontogenic Infections

Author: Ashley Zeoli

Background

Consist primarily of dental caries and peridontal disease (gingivitis and periodontitis) that can have local and systemic involvement
Streptococcus species, peptostreptococcus, Veillonella, diptheroids >80% of infections

Presentation

Associated w/ fever of unknown origin (fever > 3 weeks without etiology), bacteremia w/ seeding of heart valves and prosthetic devices
Periodontal abscess commonly encountered on wards

Evaluation

Obtain panorex, use CT for osseous structures
If needing additional assistance, consult OMFS

Management

Pyogenic odontogenic infections: parenteral therapy is favored
Immunocompetent: unasyn 3g IV q6 hours (alternative is PCN G with metro)
Immunocompromised: zosyn 4.5g IV q6 OR cefepime 2g IV q12 + metro 500mg PO q8

Additional information

Who needs antimicrobial ppx prior to dental procedures? - Does the pt have a high-risk condition or implanted device? - Yes? is the pt undergoing invasive dental procedure (manipulation of gingival tissue, periapical region of teeth, extraction, abscess drainage, routine teeth cleaning?) - Yes? Use antimicrobial ppx:: Amoxicillin 2g - No? no abx ppx needed

Pulmonary Infections

Authors: VASP, Evan Schwartz

Acute Bronchitis

Background

1-3 wks productive cough, often preceded by URI, may have wheezing/rhonchi
Distinct from chronic bronchitis (>3 mos of consecutive cough x 2 consecutive yrs)
Distinct from PNA (parenchymal consolidation, fever >100.4F, hypoxia, tachypnea)
DDx: COVID-19, post-nasal drip, GERD, undertreated/new asthma, ACE-i induced bradykinin cough, undertreated CHF, acute PE, or new lung cancer
Typically a clinical dx; CXR/labs not necessary unless PNA suspected

Management

Supportive: lozenges, cough suppressants (guaifenesin or dextromethorphan), smoking cessation. Consider albuterol inhaler for wheezing
No indication for antibiotics

Community Acquired Pneumonia (CAP)

See CAP algorithm (https://www.vumc.org/antimicrobial-stewardship-program/guidelines) on VASP website

Background

All PNA that does not otherwise meet criteria for Hospital Acquired Pneumonia (PNA that develops ≥48 hours after hospital admission), Ventilator Associated Pneumonia (PNA that develops ≥48-72 hours after endotracheal intubation), or aspiration PNA
Healthcare-associated pneumonia is no longer a clinical entity per 2016 IDSA guidelines
MRSA Risk Factors:
Recent history of MRSA
Cavitary lesion or necrotizing pneumonia
Post-influenza bacterial PNA
Pts with IDU
Severe hypoxemia requiring intubation
Pseudomonas Risk Factors:
Recent history of Pseudomonas
Bronchiectasis or structural lung disease
Both MRSA and Pseudomonas Risk Factors:
Hospitalization AND IV antibiotics in previous 90 days
Immunocompromising conditions
*Double coverage for Pseudomonas is not indicated in general population; LVQ has 82% sensitivity so not recommended unless isolate proven susceptible

Evaluation

Sputum cultures prior to abx, consider BCx in select groups (severe pna, ICU admission, cavitary disease, immunosuppression).
Rule out flu if the right season, COVID-19, consider RVP if it will change management
CURB-65 or PSI can aid in decision between outpt vs inpt therapy
CURB65: Confusion, Uremia (BUN >=19mg/dL), RR (>30/min), BP(<90/60), Age ≥ 65 If ≥ 2, hospitalization is recommended.
Consider urine pneumococcal Ag, urine Legionella Ag in severe CAP and in certain pts (e.g., neutropenia, asplenia, obstructive lung disease, hyponatremia, diarrhea, or heavy ETOH);
CRP, ESR, and pro-calc have not been shown to reliably improve outcomes; however, pro-calcitonin < 0.25 suggests against bacterial respiratory infection and antibiotic discontinuation is encouraged
PA/ lateral CXR. If immunocompromised, consider CT chest w/o contrast (does not improve outcomes)
Lobar Consolidation - likely bacterial
Interstitial Infiltrate - likely atypical vs. viral vs. non-infectious
Cavitation - concerning for fungal vs. necrotizing vs. mycobacterial

Management

Antibiotic Duration: 5-7 days (at least 5 days and improvement with clinical stability)

Outpatient management

Low Risk (no chronic heart, lung, liver, renal disease, DM, alcoholism, immunocompromise) - Amoxicillin 1g TID

High Risk - Amox/clav 875/125 mg BID - Cefuroxime 500 mg BID - Levofloxacin 750 mg daily

Inpatient management

Severity	No MRSA or Pseudomonas Risk Factors	MRSA or Pseudomonas Risk Factors
Non-Severe/Non-ICU	Preferred: Ampicillin-sulbactam 3g IV q6h OR Ceftriaxone 2g IV daily High Risk Penicillin AND Cephalosporin Allergy: Levofloxacin 750mg PO (or IV) daily If cultures are positive, target antibiotics to the recovered pathogen.	MRSA Options: Vancomycin (pharmacy consult) OR Linezolid 600mg PO (or IV) BID P. aeruginosa Options: Cefepime 2g IV q8h or Piperacillin/tazobactam 3.375g IV q8h *If MRSA or P. aeruginosa are not recovered on culture, change to routine CAP coverage. If cultures are positive, target antibiotics to the recovered pathogen.
Severe/ICU	Preferred: Ampicillin-sulbactam 3g IV q6h OR Ceftriaxone 2g IV daily + Azithromycin 500mg IV (or PO) daily OR Doxycycline 100mg IV (or PO) q12h High Risk Penicillin AND Cephalosporin Allergy: Levofloxacin 750mg IV (or PO) daily Addition of steroids per ICU protocol If RPP and Legionella urine antigen (if collected) negative, atypical coverage should be discontinued. If RPP is positive for M. pneumoniae or C. pneumoniae, doxycycline 100mg PO BID is preferred. If high suspicion for Legionella or positive urine antigen, azithromycin or levofloxacin are preferred over doxycycline.	MRSA: Vancomycin OR Linezolid (if no bacteremia) PLUS Pseudomonas: Cefepime 2g q8h or Pip/tazo PLUS Atypical: Azithromycin 500 mg IV (or PO) daily Addition of steroids per ICU protocol If RPP and Legionella urine antigen (if collected) negative, atypical coverage should be discontinued. If RPP is positive for M. pneumoniae or C. pneumoniae, doxycycline 100mg PO BID is preferred. If high suspicion for Legionella or positive urine antigen, azithromycin or levofloxacin are preferred over doxycycline.

Anaerobic Coverage: Do NOT start metronidazole or clindamycin for aspiration pneumonia. Anaerobic coverage should be considered if empyema or lung abscess detected.

Transition to PO as soon as patient able to tolerate PO medications and is clinically improving. If patient has concurrent bacteremia, transition after at least 3 days of IV antibiotics.

Additional Information

MRSA nasal swab has reported negative predictive value for MRSA pneumonia ranging 95% to >99%; consider sending and if negative, discontinue MRSA agent
CTX is generally adequate coverage for aspiration PNA without evidence of abscess, empyema, or cavitary lesion on imaging
Aspiration pneumonitis does not require abx. Rapid resolution of leukocytosis and stabilization of vitals suggest aspiration pneumonitis.
There is low sensitivity of S. pneumoniae to azithromycin (42%) and doxycycline (72%), so these should not be used as monotherapy
Check for drug interactions with linezolid (e.g., SSRI, methadone, methamphetamine use)

Hospital Acquired Pneumonia (HAP) and Ventilator Associated Pneumonia (VAP)

See HAP/VAP algorithm (https://www.vumc.org/antimicrobial-stewardship-program/guidelines) on VASP website

Background

HAP: Pneumonia that develops >48 hours after admission
VAP: Pneumonia that develops >48 hours after endotracheal intubation

Evaluation

Cultures of blood, sputum, endotracheal aspirate and/or bronchoscopy specimen
Consider MRSA nares to help with de-escalation
If there is concern for respiratory viruses: send SARS-CoV-2/influenza/RSV (RPP may be considered for immunocompromised patients)

Management

Initially cover for MRSA and Pseudomonas
Antibiotic Duration: 7 days in uncomplicated cases, although specific pathogens (e.g., Pseudomonas) may require longer duration and ID guidance
Consider ID consultation if the pt is not clinically improving on empiric therapy or if an MDR pathogen grows from culture
If no MRSA isolated and pt is improving, consider stopping vancomycin ASAP
There is concern for nephrotoxicity with combination Vancomycin and piperacillin-tazobactam, but data controversial

MRSA Coverage	Pseudomonas Coverage
Empiric Antibiotics: Vancomycin (Pharmacy dosing) or linezolid	Cefepime 2g q8h OR Piperacillin-tazobactam 3.375 q8h extended infusion

Influenza

Background

Dx often clinical w/cough, sore throat, sputum/nasal discharge, HA, fever, myalgias, and malaise; ± N/V/D. Exam with increased flushing, rarely with lower respiratory symptoms.

Evaluation

During flu season: Obtain COVID/RPP or dedicated influenza PCR; testing is more accurate if obtained within 96 hour of symptom onset
CXR if concerned for bacterial superinfection

Management

Antivirals most effective when given <48 hours from symptom onset; however, recommended to be given if symptomatic despite duration and to all hospitalized pts
Oseltamivir 75mg BID x 5 days, peramivir 600mg IV x 1 (needs renal adjustment), or baloxavir (age ≥12) 40mg once (use 80 mg if >80kg)
Amantadine and rimantadine are no longer used due to emerging resistance

Inpatient COVID-19 Management

Author: Aisha Suara

Testing

Test patients with any new fever, cough, shortness of breath, loss of taste/smell, diarrhea/vomiting, or flu-like symptoms
Asymptomatic testing for SARS-COV-2 is no longer required for routine admissions or pre-procedures
Exceptions:
Admission to 10 CCT, 11N, MCE6, and MCE7
Pre-transplant pre-procedure planning
May also be required by post-acute care facility prior to discharge
Would avoid retesting those with confirmed COVID-19 within the last 30 days unless they develop symptoms or fall within the exceptions due to risk of lingering detection without contagiousness or recurrent infection

Evaluation of Admitted Patients with Symptomatic Acute COVID-19

Please refer to the hospital's current maximum oxygen requirement allowed on the floor to ensure patient is appropriately triaged
Basic admission workup for symptomatic, confirmed COVID-19
Labs: CBC with diff, CMP, D-dimer, Ferritin, CRP, ESR, PT/INR, PTT, procalcitonin
Imaging: Portable CXR. Consider CTA PE if sudden or rapid worsening of hypoxia
Nursing: Strict I/O's to avoid pulmonary edema
Enhanced precautions (contact, airborne, eye protection)

Management

Fluid balance goal slightly net negative to even
Anticoagulation/DVT prophylaxis:
Current guidelines suggest DVT ppx on admission
Would only initiate treatment dose anticoagulation if confirmed DVT/PE

Pharmacologic therapies

Note: Therapies, indications, and contraindications are frequently changing, please see latest VUMC/VA guidelines for specific indications for these medications or others. For VUMC, REDCap form (https://redcap.vumc.org/surveys/?s=A9E7PXTCADJEA9P8) is required prior to ordering Paxlovid or Remdesivir

Nirmatrelvir/ritonavir (Paxlovid)

For use in symptomatic patients within 5 days of symptoms at high risk for progression to severe disease without significant drug interactions
Contraindications:
Risk of HIV resistance in patients with uncontrolled or undiagnosed HIV-1 infection
Substantial drug interactions
Dosing:
eGFR >60: nirmatrelvir 300 mg (two 150 mg tablets) + ritonavir 100 mg (one 100mg tablet) BID x 5 days
eGFR 30 to <60 mL/min: nirmatrelvir 150 mg (one 150 mg tablet) + ritonavir 100 mg (one 100 mg tablet) BID x 5 days
eGFR <30 mL/min: use is not recommended
Significant drug-drug interactions (discuss with Pharmacy)

Remdesivir

For use in patients hospitalized with COVID within 7 days of symptoms at high risk for progression to severe disease
Contraindications: known hypersensitivity, ALT >/= 10x ULN, on mechanical ventilation or ECMO
Dosing:
Mild to moderate COVID-19 who may be admitted for other indications but are at high risk of progression to severe COVID 19: loading dose 200mg IV x1 then 100mg IV q24h x 2 days. Course can be extending for a total of 5 days if patient progresses to severe COVID-19 (requiring supplemental oxygen)
Severe COVID-19 requiring supplemental oxygen: loading dose 200mg IV x1 then 100mg daily x 4 days
Monitoring: baseline CBC, INR, q48h CMP
Do not need to remain in the hospital to complete course of Remdesivir

Dexamethasone

For inpatient management of COVID-19 who require supplemental respiratory support (NC, non-invasive ventilation, mechanical ventilation, or ECMO)
Dosing
6mg PO/IV x 10 days; consideration of longer taper if no clinical improvement or persistently elevated CRP
12mg Po/IV daily can be considered in those requiring >=10L who are clinically worsening despite 6 mg and who are not eligible for baricitinib or tocilizumab
Contraindications: no hard contraindications, use clinical judgement if concomitant serious bacterial/fungal infection

Baricitinib (JAK inhibitor)

Eligibility determined by ID and/or Pulm/Crit
Use in those requiring >=6L or >40% FiO2, <=7 days since admission to the hospital, and/or clinical worsening despite steroids and supportive care
Contraindications: hypersensitivity, concurrent treatment with tocilizumab, dialysis, ESRD, or acute anuric kidney injury, ALT>= 10x ULN, active TB or systemic fungal infection, or pregnancy
Dosing:
Would discuss with pharmacist if patient is taking an OAT3 inhibitor, otherwise dosing is based on eGFR
For patients with eGFR > 60 ml/min: baricitinib 4 mg po daily
For patients with eGFR 30-59 ml/min, baricitinib 2 mg po daily
For patients with eGFR 15-29 ml/min, baricitinib 1 mg po daily
To be administered for 14 days or until hospital discharge
Monitoring: CBC w/ diff and CMP at baseline
Adverse events: thrombosis, elevated LFTs, severe infection 2/2 lymphopenia and neutropenia

Tocilizumab (IL-6 inhibitor)

Eligibility determined by ID and/or Pulm/Crit
Adjunctive therapy for those who are not eligible with baricitinib
Contraindications: hypersensitivity, recent hx of diverticulitis, history of bowel perforation, demyelinating disorders, ALT>= 5x ULN, ANC <500, Plt <50k, active bacterial, fungal, or viral infection other with COVID-19
DOSING: 8mg/kg, up to max of 800mg IV, once
Adverse events: Bowel perforation, elevated lipids, elevated LFTs, serious infections

Antibiotics:

Consider CAP coverage if evidence of PNA on imaging or lack of improvement despite supportive care
Can also use procalcitonin to guide decision though procal may be elevated in severe COVID-19 infection without concomitant bacterial infection

Discharge Recommendations

Typical discharge criteria for respiratory illness requiring supplemental oxygen
If patient was hospitalized FOR COVID-19, Patients should self-isolate x 20 days after the test was obtained AND until improving and fever-free x 24 hours
If hospitalized WITH COVID-19 (i.e. hospitalized for other indications and required remdesivir and/or steroids), would isolate for 10 days after test was obtained
Consider telehealth PCP f/u
May be seen in-person at clinic after they have completed the required isolation
Consider a referral to home health

Multisystem Inflammatory Syndrome in Adults (MIS-A)

Consider in those with fever with unclear etiology, history of previous COVID-19 diagnosis 2-8 weeks prior, and laboratory evidence of organ dysfunction
See VUMC COVID-19 Guidance for MIS-A for full diagnostic criteria
Treatment: IVIG, steroids, and DVT ppx

Mycobacterium Tuberculosis (MTB) and Non-tubercular mycobacterium (NTM)

Author: Ally Glover

Mycobacterium tuberculosis (MTB)

Micro profile: small, aerobic, acid-fast bacillus
Epidemiology overview: 8,331 reported TB cases in US in 2022 per CDC. Up to 13 million people living in the US with latent TB.
Terminology: some discrepancies / evolution of language around TB
Active tuberculosis (now often called Tuberculosis Disease)
Latent TB Infection (now often called Tuberculosis Infection)
Transmission: inhalation of aerosolized droplets from an infected individual
Possible outcomes of this exposure/transmission:
Immediate clearance by host defenses
Primary TB Disease
TB infection (Latent Disease)

Presentations

TB Disease (Active TB)

Primary TB (after first exposure)
Fever, cough, pleuritic chest pain
CXR: hilar/mediastinal LAD, pulmonary consolidation, pleural effusion. Some patients can present with isolated pulmonary cavitations.
Reactivation (post primary TB, years after exposure often)
Presents more insidiously: fever, cough, malaise, weight loss, dyspnea. There is an overlap with primary TB.
CXR: usually involves apical and posterior upper lobe consolidations, often with cavitations
Extrapulmonary manifestations: lymphadenitis, pericarditis (can cause tamponade), genitourinary (can cause infertility even in women), peritoneal involvement, and CNS involvement

Disseminated TB - Also referred to as miliary TB. Can range from acute to chronic in presentation. - Dissemination is more often seen in immunocompromised hosts (including patients with HIV/AIDS).

TB Infection (Latent Disease) - Asymptomatic by definition - The immune system has contained any active disease such that individuals are not infectious - CXR may show old, healed tuberculosis but patient has no history of treatment. This patient would be very high risk for reactivation.

Testing & Diagnosis

Who to test? - Clinical judgement is key - In general, think about patients about to go on TNF-alpha blocker or a similar biologic, patients with malignancies, patients with newly diagnosed or undiagnosed HIV, patients at high risk due to living conditions (unhoused individuals in shelters, incarcerated patients).

Tuberculin skin test (TST) and interferon gamma release assay (IGRA) are often used for screening purposes
If someone had the BCG vaccine, cannot use TST
If you are concerned for symptomatic TB disease, need to get 2 AFB sputum samples with Xpert testing before can come off TB precautions
Xpert MTB/RIF detects the MTB rproB gene. Also detects rifampin resistance.
- 98% sensitive for a single sputum specimen in smear-positive culture-positive cases; approximately 70% sensitive for smear negative culture-positive cases (this increases to 90% if you test 3 samples).

Treatment:

TB Infection (Latent TB):

Different options: - Rifampin (RIF) daily for 4 months (4R) - Isoniazid (INH) and RIF daily for 3 months (3HR) - INH and rifapentine (RPT) weekly for 3 months (3HP) - INH for 6-9 months (alternative if contraindication to rifamycins)

TB Disease:

Multi drug regimen for at least 6 months for pulmonary TB
INH, RIF, pyrazinamide (PZA), and ethambutol (EMB) for 2 months followed by INH and RIF for 4 more months
For CNS involvement: 12 months of therapy plus steroids
For bone and joint involvement: 6-9 months of therapy
For certain patients with drug-susceptible TB confined to pulmonary system: new recommendation that can do a 4-month course where rifapentine (RPT) and moxifloxacin (MOX)
2 months of RPT, INH, PZA, and MOX, followed by 9-weeks of RPT, INH, and MOX
If patient has HIV, remember that TB meningitis is one of the infections most likely to result in IRIS, so ART initiation is held in this case
These treatment summaries are for non-pregnant patients

Non tubercular mycobacterium (NTM)

These are mycobacteria species that do not cause tuberculosis or leprosy
Ubiquitous in the environment
Most well-known species: mycobacterium avium complex (MAC)

NTM manifestations in patients:

Pulmonary disease

Pulmonary MAC
Presents usually with cough, weight loss, fatigue
Often occurs in patients with underlying lung disease (bronchiectasis, COPD) or patients with prior TB
Another common phenotype: women > 50 who are non-smokers
More likely to have CFTR mutations
Common imaging findings: nodules, bronchiectasis, and/or cavities
Diagnosis: symptoms, imaging findings, 2 positive sputum samples with NTM growth or 1+ bronchial washing (if patient symptomatic)

Disseminated infections - Most often seen with HIV/AIDS - Disseminated MAC presents usually with fever, night sweats, weight loss - End organ involvement: bone marrow (manifesting as cell line derangements), adenopathy/hepatosplenomegaly, GI (manifesting as diarrhea, abdominal pain), and pulmonary - Diagnosis: AFB blood cultures, culture & staining/path from end organ areas of involvement (i.e. bone marrow biopsy)

NTM infections can also present as superficial lymphadenitis or skin infections

Treatment

Depends on macrolide susceptibility
For pulmonary MAC: 3 drug regimen consisting of a macrolide (usually azithromycin), a rifamycin (usually rifampin), and ethambutol.
Aminoglycoside also sometimes used depending on type of pulmonary disease
Duration of treatment is usually 15-18 months. Depends on how quickly patients can clear their cultures as you need treatment until 2 consecutive sputum cultures are negative for at least 12 months
Disseminated disease treatment is more complicated and is affected by ART often in patients with HIV, so reach out to ID
ART should be started in individuals with new HIV diagnosis as soon as MAC treatment is started (unless another co-infection prevents this due to risk of IRIS)

Sexually Transmitted Infections

Author: Lauren Waskowicz

Evaluation: Gonorrhea, Chlamydia, Trichomonas

Microbial diagnosis is preferred, rather than clinical diagnosis alone
Test of choice: NAAT of the first-catch urine in men; NAAT of vaginal swab in women
NAAT of pharyngeal or rectal swab should also be performed in patients with reported symptoms and recent sexual exposure. Note this is also routine testing in patients on PrEP.
Routine screening should be offered to sexually active patients, as many are asymptomatic
Women age < 25 years should undergo annual screening for G/C
MSW without HIV infection should undergo screening for G/C if at increased risk
MSM without HIV infection should undergo annual screening for G/C
NAATs can detect both LGV and non-LGV chlamydia, but cannot distinguish between them
ALWAYS Check CDC guidelines to confirm treatment strategy given emerging resistance: https://www.cdc.gov/std/treatment-guidelines/default.htm

Chlamydia

Background

Cause: gram negative bacteria Chlamydia trachomatis
Most individuals are asymptomatic though spectrum of dx: urethritis, cervicitis PID, conjunctivitis, perihepatitis (Fitz-Hugh-Curtis syndrome), pneumonia, proctitis, epididymitis, reactive arthritis, pharyngitis, lymphogranuloma venereum (LGV), endemic trachoma
Differential diagnosis: Neisseria gonorrhoeae, Trichomonas vaginalis, Mycoplasma genitalium

Management:

Doxycycline 100mg BID x 7 days
Alternative treatment options (for allergies/severe contraindications): azithromycin (1g PO x 1), levofloxacin (500mg PO daily x7 days), and ofloxacin (300mg BID PO x7 days)
Pts who have receptive anal intercourse with positive rectal chlamydia NAAT should receive empiric LGV therapy with doxycycline 100mg BID for 21 days rather than 7.
Pts with recent potential or confirmed exposure within the last 1-2 weeks should be treated empirically
Pts with persistent symptoms, confirmed infection, and who already underwent appropriate treatment, likely have a re-infection, rather than treatment failure. Test again.
Empiric therapy for gonorrhea should be given to pts unless NAAT is negative
Instruct patient to abstain from sexual contact until treatment course completed, test of cure not generally warranted
Partners should undergo screening and treatment. Expedited partner therapy (giving pt script for their partner(s)) IS legal in TN and can be used when the partner is unlikely to seek medical care.

Gonorrhea

Background

Gram-negative coccus Neisseria gonorrhoeae
Spectrum of disease: urethritis, cervicitis, epididymitis, proctitis, pharyngeal infections, conjunctivitis, PID, and disseminated gonococcal infection

Management

CTX is the only current abx that meets the strict treatment efficacy goals with single-dose therapy.
High dose IM ceftriaxone (<150kg 500mg IM; >150mg 1g IM)
- Same for pharyngitis or conjunctivitis
CTX allergies: Azithromycin (2g PO x1) + Gentamicin (240mg IM x1) or Gemifloxacin. Would discuss with ID.
Treatment of chlamydia must also be accompanied with gonorrhea treatment when it has not been excluded with molecular testing.
Doxycycline 100mg BID for 7 days
Pts who have persistent symptoms despite tx should be suspected of having resistant gonorrhea or Mycoplasma genitalium. Test with culture and antimicrobial susceptibility testing (with or without NAAT).
Partners should undergo screening and treatment. Expedited Partner Therapy is NOT legal for gonorrhea treatment in TN.
Instruct patient to abstain from sexual contact for 7 days following treatment, test of cure not generally warranted

Trichomonas

Background

Flagellated protozoan Trichomonas vaginalis
Most individuals are asymptomatic, although there is a spectrum of disease: urethritis or cystitis, vaginitis, cervicitis, pelvic inflammatory disease
Most common non-viral sexually transmitted infection worldwide

Management

Female: Metronidazole 500 mg BID for 7 days
Male: Single dose of 2g of Metronidazole (Four 500 mg tablets)
Due to high rates of co-infection with other STI's patients should undergo a full screening panel if Trichomonas is confirmed
Partners should undergo screening and treatment. Expedited Partner Therapy is NOT legal for Trichomonas treatment in TN.
Instruct patient to abstain from sexual contact until they and their sexual partner have completed treatment and are asymptomatic. Women should undergo retesting within 3 weeks to 3 months to ensure cure

Syphilis

Background

Caused by the spirochete, Treponema pallidum
High rate of HIV co-infection among MSM with syphilis (~42%)
Transmitted by direct contact with an infectious lesion during sex (condoms do NOT provide full protection)
Can readily cross the placenta

Evaluation

Test all pts with signs and symptoms, as well as pts who are at increased risk for acquiring infection (pts with sexual partner with early syphilis, MSM, HIV, high risk sexual behaviors, and history of commercial sex work or incarceration)
HIV testing should be offered to all pts who test positive
Pregnant pts should be screened for syphilis
There are two types of serologic tests: treponemal-specific tests (FTA-ABS, MHA-TP, TPPA, TP-EIA, CIA) and nontreponemal tests (RPR, VDRL, TRUST). VUMC utilizes Reverse Sequence Algorithm due to high number of false negatives in traditional algorithm (see diagram below for testing strategy)
Treponemal tests typically remain positive for life following infection
Nontreponemal quantifies amount of antibody present and can be used to detect titers to assess for treatment. Titers should decline after a pt has been treated. A rise in titers (4 fold) in a previously treated pt should be concerning for new infection.
Requires a humoral response, so can be false negatives if immunocompromised
False positives: autoimmune diseases, pregnancy, other infections
Neurosyphilis can occur at any time after infection. All newly diagnosed pts with syphilis should have a full neurologic exam and if any abnormalities should have an LP sent for CSF-VDRL (specific, but not as sensitive) with reflex to FTA-ABS (sensitive, but not as specific)
Any pts with syphilis and vision changes should get an ophthalmology evaluation for fundoscopic exam.

Interpretation of Testing:

	+Treponemal	-Treponemal
+Non-treponemal	Diagnostic of syphilis (completely new or potentially re-infected)	Likely false positive
-Non-treponemal	Likely history of successfully treated syphilis	Likely not syphilis or false negative (due to prozone effect*)

*Prozone effect: when there is an overabundance of antibodies and they interfere with clumping/formation of antigen/antibody complex so agglutination cannot be visualized

Management

When positive Treponemal Ab + low positive or negative RPR, it is important to determine prior testing and treatment.
For obtaining historical syphilis titers and past treatment records, email [email protected] with responses to be expected same day or next business day
To assess treatment efficacy, goal of a fourfold decrease in titer after treatment

Stage	Symptoms	Treatment	Treatment Alternatives
Primary	Painless (but can be painful) chancre at inoculation site with regional lymphadenopathy	PCN G benzathine 2.4 million units IM x1	Doxycycline 100mg PO BID x 14 days OR Ceftriaxone 1-2g daily IM or IV x 10-14 days OR Tetracycline 500mg PO QID x 14 days OR Amoxicillin 3g BID and probenecid 500mg BID x 14 days
Secondary	Systemic illness with rash (palms, soles), fever, malaise, alopecia, hepatitis, mucous patches, condyloma, pharyngitis
Early Latent	Infected, but no symptoms. Occurs within one year of initial infection.
Tertiary	Symptomatic late syphilis (CV system, gummatous dx)	PCN G benzathine 2.4 million units IM weekly x3 weeks	Doxycycline 100mg PO BID x 4 weeks OR Ceftriaxone 2g daily IM or IV x 10-14 days
Late Latent / Syphilis of Unknown Duration	Infected, but no symptoms. Occurs >1 year after initial infection. Refer to last known negative test. Date of infection unknown
Neurosyphilis	Can occur at any time. Early: asymptomatic or symptomatic meningitis, vision loss, hearing loss Late: brain and spinal cord manifestations (dementia, tabes dorsalis) Treat ocular syphilis like neurosyphilis	Aqueous PCN G 4 million units IV q4h x 10-14 days	PCN G procaine 2.4 million units IM daily and probenecid 500mg PO QID x 10-14 days If PCN allergic, desensitize Ceftriaxone 2g daily IM or IV x 10-14 days

Skin and Soft Tissue Infection (STI)

Author: VASP

Cellulitis

See SSTI algorithm on VASP website (https://www.vumc.org/antimicrobial-stewardship-program/guidelines)

Background

DDx: erysipelas, pyomyositis, necrotizing fasciitis, osteomyelitis, venous stasis, shingles, gout
Pathogens: Streptococcus species: Group A (most common), B, C, G, Staphylococcus aureus (including MSSA and MRSA)
Non-purulent, lymphangitis, or erysipelas? Think Streptococcus
Purulence (abscess or boil)? Think Staphylococcus
Strep anginosus is a strep species that can cause pus formation
Unique clinical scenarios and associated organisms/organisms to consider:
Dog/cat bite: Pasteurella multicoda, Capnocytophaga canimorsus
Human bite: Eikenella corrodens, oral anaerobes, S. aureus
Fresh water exposure: Aeromonas hydropholia, Plesiomonas shigelloides
Salt water exposure: Vibrio vulnificus
Neutropenia, presence of ecthyma: Gram negatives (Pseudomonas aeruginosa)
Immunocompromised: Fungal (Candida spp, Cryptococcus), Nocardia, non-tubercular mycobacteria)
Burn pts: Pseudomonas, Acinetobacter, Fusarium

Evaluation

Outline border of erythema and obtain urgent surgery consultation if rapid spread of infection, crepitus, air in tissues, or pain out of proportion to exam
Blood cultures (BCx): ONLY needed if systemic signs of infection or immunocompromised (most pts will not need BCx or imaging)
US for underlying abscess
CT/MRI w/contrast: if necrotizing fasciitis, pyomyositis or osteomyelitis suspected
Bilateral lower extremity cellulitis is RARE and warrants consideration of non-infectious etiologies
Elevation test: if erythema improves after elevating leg above the level of the heart for 1-2 minutes, less likely to be infectious cellulitis

Management

Abx for 5 days for uncomplicated; can extend to 10-14 days if little to no improvement, more extensive/serious infection, or if immunosuppressed
Typically improvement is not seen until >48 hours of antibiotics, usually longer
Provide anti-Staphylococcal antibiotics for purulent cellulitis in addition to I&D, if abscess present
Clinical appearance may often appear to worsen initially despite adequate therapy
Always elevate the extremity for more rapid clinical improvement!

	No Staph suspected	MSSA	MRSA
Mild/Moderate (Outpt)	Cephalexin 500 QID Amoxicillin 500 TID Cefadroxil 1g BID	Cephalexin 500 QID Cefadroxil 1g BID Dicloxacillin 500 QID	*Clindamycin 300-450 mg q6h TMP/SMX 1-2 DS tabs BID Doxycycline 100 mg BID
Severe (Inpt)	Cefazolin 2g q8h CTX 2g q24h	Cefazolin 2g q8h	Vancomycin (dose per PK) PO step down: TMP/SMX 1-2 DS tabs BID Doxycycline 100 mg BID Linezolid 600 mg BID Stepdown to above PO options once: • Staph aureus bacteremia is ruled out • Clinical stability obtained > 24 hours • Patient is tolerating oral therapy

*Consider for PCN allergy; check antibiogram (VUMC vs VA) for Staph sensitivities; clindamycin should NOT be used for strep coverage

PO step down: cephalexin 500 mg q6h or 1000mg q8h

Necrotizing Fasciitis

Background

Infection of the deeper soft tissues that causes necrosis along the muscle fascia and overlying subcutaneous fat that is rapidly progressive and lethal if not addressed
Clinical cues include rapid spread, pain out of proportion to exam, crepitus and hemorrhagic bullae
LRINEC score used to screen for necrotizing soft tissue infection

Evaluation/Management

SURGICAL EMERGENCY!
STAT consult to surgical service for emergent debridement (generally EGS vs ortho)
Imaging does NOT rule out necrotizing fasciitis and should not delay these consultations
CT is the best imaging modality
ID consult
Empiric antibiotics
Preferred: linezolid 600 mg IV BID + piperacillin-tazobactam 3.375g IV q8h extended infusion
For severe penicillin allergy: linezolid 600 mg IV BID + cefepime 2g IV q8h + metronidazole 500 mg IV BID
For severe penicillin and cephalosporin allergy: linezolid 600 mg IV BID + levofloxacin 750 mg IV q24h + metronidazole 500 mg IV BID
If patient cannot receive linezolid due to allergies, or multiple serotonergic drug interactions: vancomycin + piperacillin-tazobactam 3.375g IV q8h extended infusion + clindamycin 900mg IV q8h