Bacterial Pneumonias

In the past, pneumonias were the most common cause for hospitalization of HIV-infected patients. Acute onset of cough and fever with a lobar radiographic infiltrate suggests bacterial pneumonia. Not only do HIV-infected patients have rates of pneumonia resulting from Streptococcus pneumoniae that are 150-fold greater than those in the non-HIV-infected population, but they also are at higher risk for recurrences. Because immunologic response to the polysaccharide antigens is impaired at CD4⁺ lymphocyte counts less than 500 cells/μL and in patients with detectable viral loads, pneumococcal vaccination should not be considered as protective in HIV-infected individuals. Furthermore, HIV-infected patients with pneumococcal pneumonia have a greater risk for bacteremia, meningitis, and other complications compared to than non-HIV-infected individuals.

Likewise, Haemophilus influenzae pneumonia occurs 100 times more often in HIV-infected versus non-HIV-infected patients. Because the organisms for most of these Haemophilus species cannot be typed, H. influenzae type b vaccine is also not protective. Although other pyogenic bacteria are less common causes of pneumonia in HIV-infected patients, Pseudomonas aeruginosa pneumonia may be seen in late stages of disease (usually associated with a CD4⁺ lymphocyte count < 100 cells/μL, cavitary lung disease, or prior treatment with broad spectrum antibiotics). In addition, Staphylococcus aureus, including methicillin-resistant strains, is an increasingly common cause of community-acquired pneumonia in HIV-infected patients and should be suspected in patients with a history of viral respiratory infection, intravenous drug use, or severe bilateral infiltrates (Chapter 65). Legionella pneumonia occurs infrequently, but its incidence is increased 40-fold in HIV-infected versus non-HIV-infected patients.

Empiric treatment of HIV patients with community-acquired pneumonia requiring ICU admission includes an intravenous (IV) beta-lactam plus either azithromycin or a respiratory fluoroquinolone (moxifloxacin or levofloxacin 750 mg daily) (Chapters 18 and 65). For patients with those risk factors for Pseudomonas pneumonia listed above, the preferred beta-lactam agents include piperacillin-tazobactam, cefepime, imipenem, and meropenem. Vancomycin or linezolid should be added to the antibiotic regimen if Staphylococcus is suspected.

Pneumocystis Pneumonia

Acquired immunodeficiency syndrome (AIDS) is the most common predisposing cause of Pneumocystis (carinii) jirovecii pneumonia (PCP). In the absence of chemoprophylaxis, more than 80% of patients with AIDS develop PCP in their lifetimes. Its likelihood is affected by the degree of immunologic impairment. In HIV-infected adults, this disease most commonly arises in individuals with CD4⁺ lymphocyte counts between 50 and 75 cells/μL and is uncommon in individuals with CD4⁺ lymphocyte counts > 200 cells/μL or a CD4⁺ lymphocyte percentage > 20% of the absolute lymphocyte count.

Early diagnosis and therapy for PCP are associated with a more favorable outcome. Prognosis is worse if the patient has a large alveolar-arterial (A-a) oxygen difference (Pao₂-Pao₂) at presentation, extensive infiltrates on chest radiographs, neutrophilia in a bronchoalveolar lavage (BAL) specimen, elevated serum lactate dehydrogenase (LDH) levels ( > 500 IU/L), worse acute physiologic derangements, or chronic comorbidities.

Spontaneous pneumothorax is the most common complication and may occur in up to 10% of patients with PCP. The resulting bronchopleural fistulas may need chemical pleurodesis for closure.

Mycobacterial Infections

HIV infection is the most significant predisposing factor for reactivation of latent Mycobacterium tuberculosis (TB) infection. Up to 50% of HIV-infected patients who are infected with TB eventually develop active TB. Although it occurs most commonly when a patient’s CD4⁺ lymphocyte count is < 350 cells/μL, it can occur at higher CD4⁺ counts, with a presentation similar to TB in non-HIV-infected patients, including subacute or chronic onset of fever, weight loss, cough, chest pain, and shortness of breath.

Patients with low CD4⁺ lymphocyte counts also have a high risk of extrapulmonary TB (40% to 80% of TB cases). Disseminated TB and lymphadenitis are the two most common presentations of extrapulmonary disease. Disseminated disease may present acutely with hypotension and respiratory distress. TB lymphadenitis is most commonly located in cervical, supraclavicular, or axillary nodes, but intrathoracic and intra-abdominal nodes can be seen. Central nervous system (CNS) infection occurs in 5% to 10% of HIV-infected patients with TB.

Chest radiographs of active TB infection vary by level of immunosuppression. Patients with high CD4⁺ counts often have apical cavity disease. Those with low counts infrequently have cavitation but more often have lower lobe consolidation, intrathoracic adenopathy, miliary infiltrates, and pleural effusions.

Reactivity to tuberculin skin testing is inversely related to CD4⁺ counts. Among patients with AIDS and active TB, only 10% to 30% of patients will have a skin test reaction that is greater than or equal to 10 mm of induration. Sputum is positive by microscopy for acid-fast bacilli (AFB) in 40% to 65% of HIV-infected patients with active TB, and it is positive by AFB culture in 75% to 95% of patients. For patients who have not had a diagnosis made from sputum, BAL is diagnostic by AFB smear in 7% to 20% of patients and by culture in 52% to 89% of individuals, whereas transbronchial biopsy specimens result in positive AFB smears in 10% to 39% of patients and in positive cultures in 42% to 85% of individuals.

TB should be considered in the differential diagnosis of any suspected infection in an HIV patient born in the developing world. Patients with diagnosed or suspected TB should be started on four-drug therapy as soon as possible, with isoniazid, rifampin, ethambutol, and pyrazinamide, pending drug susceptibility testing. Resistance to first-line TB agents should be suspected in patients with a history of previous TB treatment, poor adherence, homelessness, sputum smear positivity after 2 months of TB therapy or culture positivity after 3 months of therapy, and birth or residence in an area of the world where multidrug resistant (MDR)-TB is endemic. In such cases, consideration should be given for the addition of two additional agents, typically a fluoroquinolone and amikacin. Adjunctive steroids should be administered for CNS or pericardial infection, beginning with IV dexamethasone 0.3 to 0.4 mg/kg followed by a switch to oral therapy with clinical improvement and a slow taper. There are numerous drug-drug interactions between the rifamycins and antiretroviral drugs in multiple therapeutic classes. Modification of antiretroviral therapy may be required in patients started on rifampin. Despite these drug-drug interactions, a rifamycin should always be used to treat TB in patients with HIV infection owing to improved outcomes.

Among the nontuberculous mycobacteria, Mycobacterium avium complex (MAC) and Mycobacterium kansasii are the most common causes of pulmonary infection. Although isolated pulmonary disease can occur, MAC more commonly presents with disseminated disease as well as signs and symptoms of chronic disease (prolonged fever, weight loss, diarrhea, cytopenias, and low albumin levels). When MAC presents as pulmonary disease, the chest radiograph typically shows bilateral, interstitial-nodular infiltrates, indistinguishable from PCP. MAC may be a co-pathogen or colonizer in HIV-infected patients with other causes of pneumonia. Under these circumstances, the organism is often cultured from a BAL specimen as a single or rare colony and requires no treatment. M. kansasii infection presents primarily as pulmonary disease.