Basics
Description
Unusual infections that occur when host suffers a decrease in resistance against normally nonpathogenic organisms
Etiology
- Occurs in HIV patients when the CD4 T-lymphocyte count falls below 200 cells/mm3 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 andα-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 PCO2 <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 & Interpretation
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/ ΌL
- ANC = WBC (cells/ ΌL) percent (PMNS + bands)/100
- Cultures (aerobic, anaerobic, fungal, viral as indicated):
- Urine
- Blood
- Wound
- Fecal
- CD4 count:
- Absolute lymphocyte count (ALC) <1,000/ ΌL predicts CD4 <200 if CD4 unknown
- ALC = WBC (cells/ ΌL) 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
Followup 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. Rosens 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.
Codes
ICD9
- 018.90 Miliary tuberculosis, unspecified, unspecified
- 136.3 Pneumocystosis
- 136.9 Unspecified infectious and parasitic diseases
- 007.4 Cryptosporidiosis
- 078.5 Cytomegaloviral disease
- 115.90 Histoplasmosis, unspecified, without mention of manifestation
- 117.5 Cryptococcosis
- 176.9 Kaposis sarcoma, unspecified site
ICD10
- A19.9 Miliary tuberculosis, unspecified
- B59 Pneumocystosis
- B99.9 Unspecified infectious disease
- A07.2 Cryptosporidiosis
- B25.9 Cytomegaloviral disease, unspecified
- B39.9 Histoplasmosis, unspecified
- B45.9 Cryptococcosis, unspecified
- C46.9 Kaposis sarcoma, unspecified
SNOMED
- 61274003 Opportunistic infectious disease (disorder)
- 75549005 Infection by Pneumocystis jiroveci
- 182159002 Disseminated tuberculosis (disorder)
- 58777003 Infection by Cryptosporidium (disorder)
- 109385007 Kaposis sarcoma (disorder)
- 12962009 Histoplasmosis (disorder)
- 28944009 Cytomegalovirus infection (disorder)
- 422031005 Opportunistic mycosis associated with AIDS (disorder)
- 42386007 Cryptococcosis (disorder)