What are the causes and treatment options for pneumonia in patients with Human Immunodeficiency Virus (HIV)?

Causes and Treatment of Pneumonia in HIV Patients

HIV-infected patients should receive combination antibiotic therapy for bacterial pneumonia, with outpatients receiving an oral beta-lactam plus an oral macrolide, and never macrolide monotherapy due to increased risk of drug-resistant Streptococcus pneumoniae. 1, 2

Common Causes of Pneumonia in HIV Patients

Bacterial Pathogens

• Streptococcus pneumoniae - Most common bacterial cause 1
• Haemophilus influenzae - Second most common bacterial cause 1
• Pseudomonas aeruginosa - More common in patients with:
  • CD4+ <50 cells/μL
  • Structural lung disease
  • Systemic corticosteroid therapy
  • Recent broad-spectrum antibiotic use
  • Prior hospitalization 2
• Staphylococcus aureus (including MRSA) - Consider in severe cases 2

Opportunistic Pathogens

• Pneumocystis jirovecii (PCP) - Most common opportunistic pneumonia in HIV, especially with CD4 counts <200 cells/μL 3, 4
• Mycobacterium tuberculosis - Must be considered, especially in cavitary pneumonia 2
• Fungal pathogens (Cryptococcus, Aspergillus) - More common with severe immunosuppression 2

Diagnostic Approach

Initial Evaluation

1. Assess disease severity - Pulse oximetry or arterial blood gas within 8 hours of presentation 2
2. Chest imaging - Radiograph or CT scan to identify patterns suggestive of specific etiologies 2
3. Microbiologic studies (collect before antibiotics):
   • Sputum for Gram stain, bacterial culture, AFB smear, fungal stain
   • Blood cultures (higher incidence of bacteremia in HIV patients)
   • Consider specific pathogen testing (Legionella/Pneumococcal urinary antigens) 2
4. CD4+ count - Critical for risk stratification and treatment decisions 2

Advanced Diagnostics

• Bronchoscopy with BAL - If sputum samples inadequate or diagnosis unclear 2
• Consider TB testing - Three sputum specimens for AFB smear/culture; molecular testing (GeneXpert MTB/RIF) for rapid diagnosis 2

Treatment Algorithm

Outpatient Treatment

• First-line: Oral beta-lactam plus oral macrolide (AII) 1

  • Preferred beta-lactams: High-dose amoxicillin, amoxicillin-clavulanate
  • Alternative beta-lactams: Cefpodoxime, cefuroxime
  • Preferred macrolides: Azithromycin, clarithromycin
  • Alternative to macrolide: Oral doxycycline (CIII) 1

• For penicillin allergy: Oral respiratory fluoroquinolone (moxifloxacin, levofloxacin 750 mg/day, or gemifloxacin) (AII) 1

  • Use fluoroquinolones with caution in patients with suspected TB 1, 2

Non-ICU Inpatient Treatment

• First-line: IV beta-lactam plus a macrolide (AII) 2

ICU Treatment

• First-line: IV beta-lactam plus either IV azithromycin or IV respiratory fluoroquinolone (AII) 2
• For penicillin allergy: Aztreonam plus IV respiratory fluoroquinolone 2
• If MRSA suspected: Add vancomycin or linezolid 2

PCP Treatment

• First-line: Trimethoprim/sulfamethoxazole (TMP-SMX) 4
• Adjunctive therapy: Corticosteroids for moderate-to-severe PCP (PaO2 <70 mmHg or A-a gradient >35 mmHg) 4
• Alternative agents for TMP-SMX intolerance: Dapsone plus trimethoprim, clindamycin plus primaquine, atovaquone, or pentamidine 4

Important Considerations

Drug Interactions and Adverse Effects

• Azithromycin: Risk of QT prolongation, especially in patients with:

  • Known QT prolongation
  • History of torsades de pointes
  • Uncompensated heart failure
  • Concurrent use of Class IA/III antiarrhythmics 5

• Dapsone: Risk of hemolysis in G6PD deficiency; monitor liver function 6

• Monitor for drug interactions between antibiotics and antiretroviral medications, particularly with rifamycins if TB treatment is initiated 2

Prevention Strategies

1. Antiretroviral therapy - Early initiation decreases pneumonia risk 7
2. Vaccinations:
   • Pneumococcal vaccine for all HIV-infected patients 1, 2
   • Annual inactivated influenza vaccine 1
3. PCP prophylaxis when CD4 counts <200 cells/mL 2
4. Smoking cessation - Smoking increases risk of bacterial pneumonia and PCP 1, 8
5. Reduction of substance use - IDU and alcohol use increase pneumonia risk 1

Monitoring and Follow-up

• Clinical response typically within 48-72 hours of appropriate therapy 2
• Consider switching from IV to oral therapy when patient is clinically stable 2
• Radiographic improvement may lag behind clinical improvement 2
• Consider immune reconstitution syndrome in patients recently started on antiretroviral therapy 2

Remember that no HIV-infected patient should receive macrolide monotherapy due to the increased risk of drug-resistant Streptococcus pneumoniae, even if they are already receiving a macrolide for MAC prophylaxis 1.