ETIOLOGY
- Occurs in HIV patients when the CD4 T-lymphocyte count falls below 200 cells/mm
3
or <14% of the total lymphocyte count:
- Pneumocystis jiroveci
pneumonia (PCP)
- Disseminated tuberculosis
- Cryptosporidiosis
- Microsporidiosis
- Isosporiasis
- Toxoplasmosis
- Histoplasmosis
- Cryptococcosis
- Mycobacterium avium
complex
- Tuberculosis pericarditis or meningitis
- Cytomegalovirus
- Human herpesvirus-8 (Kaposi sarcoma)
- JC virus (progressive multifocal leukoencephalopathy)
- Hepatitis B virus
- Penicilliosis marneffei
- Bacterial species
- Cell-mediated deficiency:
- Hematologic malignancies
- Lymphoma
- High-dose glucocorticoid therapy
- Autoimmune disorders
- Viral infections
- Cytotoxic drugs/chemotherapy
- Radiation therapy
- Associated with:
- Legionella
- Nocardia
- Salmonella
- Mycobacteria
- Neutrophil impairment/depletion:
- Cytotoxic drugs
- Aplastic anemia
- Drug reactions:
- Neoplastic invasion of bone marrow
- Arsenic
- Penicillin
- Chloramphenicol
- Procainamide
- Vitamin deficiencies
- Associated with:
- Staphylococcus
and α-hemolytic
Streptococcus
- Enteric organisms and anaerobes
- Invasive aspergillosis
DIAGNOSIS
SIGNS AND SYMPTOMS
- New or worsening fatigue
- Tachypnea
- Fever
- Chills
- Night sweats
- Pulmonary source of infection:
- Genitourinary source of infection:
- Dysuria
- Increased frequency
- Urinary retention
- GI source of infection:
- Abdominal pain
- Vomiting
- Diarrhea
- Bleeding
- Jaundice
- CNS sources of infection:
- Confusion
- Focal neurologic deficits
- Headache
- Seizure
History
- History for HIV/AIDS (recent CD4 count)
- History of malignancy with active treatment
- History of organ transplant
- History of autoimmune disorder
- Use of cytotoxic drugs
- Use of high-dose glucocorticoid therapy
Physical-Exam
- Complete, detailed physical exam indicated as signs of infection in the immunocompromised patient may be subtle.
- Signs of systemic inflammatory response syndrome:
- Temperature >38°C or <36°C
- Heart rate >90 bpm
- Respiratory rate >20 breaths per minute or PCO
2
<32 mm Hg
- Septic shock
- Focal neurologic deficits
- New murmur
- Ambulatory hypoxia in PCP pneumonia
- Rales and/or rhonchi in pneumonia
- Skin/mucosa defects as a portal of entry.
- Oropharyngeal candidiasis as an indicator of immune suppression
ESSENTIAL WORKUP
Full workup indicated owing to impaired immunity:
- Signs of infection in the immunocompromised patient may not be present
- Can present with subtle signs with rapid deterioration
- Signs such as fever must lead to a full evaluation of patient
- Thorough physical exam is critical to search for source of infection
DIAGNOSIS TESTS & NTERPRETATION
Lab
- CBC with differential for neutropenia or leukocytosis:
- WBC >12,000 or <4,000 are criteria for the systemic inflammatory response score
- Neutropenia:
- Absolute neutrophil count (ANC) <1,500/μL
- ANC = WBC (cells/μL) × percent (PMNS + bands)/100
- Cultures (aerobic, anaerobic, fungal, viral as indicated):
- Urine
- Blood
- Wound
- Fecal
- CD4 count:
- Absolute lymphocyte count (ALC) <1,000/μL predicts CD4 <200 if CD4 unknown
- ALC = WBC (cells/μL) × percent lymphocytes/100
- Urinalysis for presence of WBC, nitrite, leukocyte esterase
- Electrolytes, BUN/creatinine, glucose; anion gap acidosis suggests severe infection
- VBG for acidosis
- Lactate level; elevated value suggests serious infection
- PT/PTT for evidence of disseminated intravascular coagulation
- Lactate dehydrogenase (LDH); elevated in patients with PCP
Imaging
- CXR:
- Nonspecific for predicting a particular infectious etiology
- Pneumonia:
- Segmental or subsegmental infiltrate
- Air bronchograms
- Abscess
- Cavitation
- Empyema
- Pleural effusion
- PCP:
- Classically reveals bilateral interstitial or central alveolar infiltrates
- Radiograph normal in up to 25% of patients
- High-resolution chest CT:
- Early studies show high sensitivity for PCP in HIV-positive patients
- Reveals patchy ground-glass attenuation
- Head CT: Contrast-enhancing lesions in
Toxoplasma gondii
encephalitis
- Abdominal and pelvic CT with contrast:
- Indicated if a GI source of infection is suggested by the clinical exam
Diagnostic Procedures/Surgery
Lumbar puncture:
- CSF analysis if signs of CNS infection
- Diagnostic paracentesis:
- Immunocompromised liver patients for SBP
TREATMENT
INITIAL STABILIZATION/THERAPY
- Check airway, breathing, and circulation
- Initiate 0.9% normal saline IV 500 mL bolus for hypotension
- Oxygen
- Cardiac monitor for unstable vital signs
- Early initiation of antibiotic therapy
ED TREATMENT/PROCEDURES
- Strict isolation
- Antibiotics: Combination of expanded-spectrum penicillin (mezlocillin, ticarcillin, piperacillin) and aminoglycoside (amikacin, tobramycin):
- Monotherapy with a 3rd-generation cephalosporin (ceftazidime, cefepime), fluoroquinones (levofloxacin, gatifloxacin), or other broad-spectrum antimicrobials (imipenem/cilastatin) may be considered if aminoglycosides contraindicated
- Vancomycin if there is a high prevalence of methicillin-resistant organisms in the area
- Antifungals (amphotericin B, fluconazole) if patient is on adequate antibiotics for 1 wk
- Trimethoprim/sulfamethoxazole for suspected PCP (alternatives: Pentamidine, clindamycin + primaquine)
- Steroids: Prednisone in PCP with hypoxemia
MEDICATION
- Amphotericin B: 0.25 mg/kg/d IV
- Cefepime: 1–2 q12h IV
- Ceftazidime:
- Adults: 1–2 g IV q8–12h
- Pediatric: 100–150 mg/kg/24h IV q8–12h
- Fluconazole: 400 mg 1st dose, then 200–400 mg/d IV (peds: 6–12 mg/kg/24h IV q12h)
- Gatifloxacin: 400 mg/d IV
- Imipenem/cilastatin: 500–1,000 mg IV q6–8h, max. 50 mg/kg/d or 4,000 mg/d
- Levofloxacin: 500 mg/d IV
- Vancomycin: 1–2 g IV q12h (peds: 10–50 mg/kg/24h IV q6h
- Trimethoprim: 15–20 mg/kg + sulfamethoxazole: 75 mg/kg PO or IV div. q8h
- Prednisone: 40 mg PO BID × 5 days, then 40 mg PO QD × 5 days, then 20 mg PO QD × 11 days
*start within 72 hr of antimicrobials for PCP
FOLLOW-UP
DISPOSITION
Admission Criteria
Suspected or confirmed systemic infection
Discharge Criteria
Systemic infection excluded
Issues for Referral
Consider infectious disease consultation
FOLLOW-UP RECOMMENDATIONS
Patients with systemic opportunistic infections should be admitted to the hospital
PEARLS AND PITFALLS
- Signs of infection in the immunocompromised patient may not be present
- Can present with subtle signs with rapid deterioration
ADDITIONAL READING
- Fishman JA. Infection in solid-organ transplant recipients.
N Engl J Med
. 2007;357(25):2601–2614.
- Kaplan JE, Benson C, Holmes KK, et al. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: Recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America.
MMWR Recomm Rep
. 2009;58(RR-4):1–207; quiz CE1–4.
- Rothman RE, Marco CA, Yang S. AIDS and HIV infection. In: Marx JA, ed.
Rosen’s Emergency Medicine
. 7th ed. Boston, MA: Elsevier; 2009:130.
- Shapiro NI, Karras DJ, Leech SH, et al. Absolute lymphocyte count as a predictor of CD4 count.
Ann Emerg Med
. 1998;32(3):323–328.
- Tan IL, Smith BR, von Geldern G, et al. HIV-associated opportunistic infections of the CNS.
Lancet Neurol
. 2012;11(7):605–617.