P.carinii used to be the most common cause of pneumonia in HIV patients, however now it is bacterial pneumonia [Chest 120: 1888, 2001]. CMV, mycobacterium, and MAI can also cause pneumonia in this population. Most common isolates are encapsulated organisms – S. pneumoniae, H. influenza (100x the normal rate), and S. aureus [Chest 117: 1017, 2000]. The pattern of infiltration is NOT pathogen-specific. P.carinii pneumonia is actually treated similarly to ARDS with the exception of antibiotic coverage (TMP-SMX). Steroid therapy has been shown to help patients with P.carinii but only if given within 72 hours of starting antibiotics [NEJM 323: 1500, 1990]
Cryptococcal meningitis occurs in 10% of HIV patients, usually in the late stages of disease. Fever and headache are found in 85% of cases. LP is required for diagnosis. India ink has a 75% sensitivity, CSF cultures and antigen titers 90%. Treat with amphotericin, although there was some preliminary data that said fluconazole was as effective [NEJM 326: 83, 1992] Toxoplasma is the most common neurologic disorder in HIV patients, with clinical evidence in 10% and autopsy evidence in 30%. 60% will have focal neurologic deficits and up to 30% will have seizures [Clin Crit Care 9: 49, 1993]. Treat with phyrimetamine, folinic acid, and clindamycin.
Neutropenia is most concerning after chemotherapy or bone marrow suppression – that following viral infections or other causes < 10 days do not usually lead to an increased infection risk [NEJM 341: 893, 1999]. The major concern here is Gram-negative infection, which is usually not a major risk until PMN < 100/mm3 [Infect Med, April: 39, 1992]. In fact, 2/3 of neutropenic patients with new-onset fever do not have documented infection. In those that do have an infection, Gram (+) organisms (esp. coag negative staph) are the most common causes – bacteremia occurs in only 10-15%. A recent study showed that 42% of febrile neurtopenic patients with pulmonary infiltrates have a fungal infection, and that 18% of these patients have no infection, highlighting the need for bronchoscopy in these patients [Mayo Clin Proc 80: 1414, 2005] – sputum is notoriously unreliable for detecting fungal growth.
There are several options for empiric monotherapy – the NCI at one time endorsed ceftazidime (which does not cover Gram-positives). Imipenem is a good choice but often avoided because of its risk for seizures [Ann Intern Med 115: 849, 1991]. Combination regimens are used when Pseudomonas is suspected. If these patients have fever + infiltrates, one should suspect Legionella, mycolplasma, pneumocystis, and/or CMV. Fever > 1 week despite antibiotics suggests invasive fungal infection, at which point amphotericin should be started. To diagnose invasive candidiasis, isolates must be found in three sites (ex. urine, sputum, vascular catheter tips).
Infections in the first few weeks are usually bacterial, but after 1 – 3 months are generally opportunistic (CMV, candida, other fungi). CMV requires histologic diagnosis (cultures of blood and urine are unreliable [Ann Intern Med 118: 12, 1993]). CMV pneumonia can look a lot like P.carinii pneumonia – treat first with ganciclovir, and follow with foscarnet if needed (20% of foscarnet will develop adverse reactions, including hypomag/calcemia/phosphatemia, anemia, and renal insufficiency).