Page 905 - Hall et al (2015) Principles of Critical Care-McGraw-Hill

636 PART 5: Infectious Disorders

leading to a recommendation for the preferential use of efavirenz use to a syndrome resembling septic shock (10% of patients) with respira-
in ART regimens in coinfected patients on rifampin-based regimens. tory and multiorgan failure. Chest radiographs reveal diffuse infiltrates
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The use of PI is contraindicated in patients receiving rifampin-based (interstitial or reticulonodular) in approximately half the patients, but
regimens due to profound decreases in plasma concentrations of PIs. radiologic findings are normal in one-third of patients. A rapid pre-
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Accordingly, alternative rifamycins such as rifabutin are recommended sumptive diagnosis can be obtained by demonstrating the organism in a
in patients who require PI-based ART. The use of rifabutin is limited buffy coat smear (30% sensitivity), bone marrow biopsy, or occasionally
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by cost in the developing world. other tissues. The small intracellular yeast forms may be seen within leu-
In addition, there is remaining debate regarding optimal timing for kocytes. The diagnosis is confirmed by fungal culture (blood, bone mar-
initiation of antiretroviral therapy in patients with TB. The risks of tox- row, respiratory tract specimens, lymph node, or skin biopsy), although
icities and tuberculosis-related immune reconstitution syndrome must a positive result may take several weeks. Complement-fixation titers
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be balanced with consideration of the risk of increased mortality if ART are negative in up to 30% of non-AIDS patients with histoplasmosis.
is delayed. Similarly, in AIDS patients, a negative serology for histoplasmosis does
not reliably exclude the disease. However, antigen detection in serum
OTHER CAUSES OF PULMONARY INFILTRATES and urine is rapid and reliable, but the test is not widely available, and
specimens must be sent to the reference laboratory. A helpful clue to
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IN HIV-INFECTED INDIVIDUALS the diagnosis of disseminated histoplasmosis is the presence of a markedly
■ CYTOMEGALOVIRUS DISEASE elevated serum LDH concentration (>600 IU in 73% of patient in one
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CMV is commonly isolated from cultures from BAL samples in patients series), which may also be seen in AIDS-related disseminated toxoplas-
mosis. A prospective, double-blind study in moderate to severe AIDS-
with underlying PJP, but is not likely a pathogen in this setting. related disseminated histoplasmosis demonstrated greater efficacy and
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Patients with confirmed PJP respond to anti-Pneumocystis treatment significantly increased survival with liposomal amphotericin B (3 mg/kg
whether or not CMV is also recovered in BAL specimens. However, per day) compared with conventional amphotericin B (0.7 mg/kg per day)
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the prominent role of CMV as a gastrointestinal or ocular pathogen as induction therapy. Itraconazole is effective therapy for patients with
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among these patients is clearly recognized. mild to moderate disease. 117,126
In advanced HIV infection, CMV can occasionally cause inter-
stitial pneumonitis. However, this diagnosis must be made by tissue ■ COCCIDIOIDOMYCOSIS
biopsy demonstrating evidence of CMV cytopathic effect (ie, intra- The endemic zone for coccidioidomycosis in North America is limited
nuclear and intracytoplasmic inclusions) and excluding other respira- to the southwestern United States and extends into northern Mexico.
tory pathogens. Presentation of CMV infection is similar to that of Coccidioidomycosis is an important opportunistic infection in endemic
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PJP (dry cough, dyspnea, and diffuse infiltrates on chest radiograph). areas, occurring in 6% of HIV-infected patients in Arizona during the
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Appropriate therapy for CMV is intravenous ganciclovir with consider- pre-ART era (before 1996), either as reactivation disease, but primarily
ation of step-down to oral valganciclovir. due to recent acquisition. 127,128 Most patients have a CD4 count of less
■ FUNGAL INFECTIONS IN THE HIV-INFECTED PATIENT than 250 cells/µL at the time of diagnosis. This infection should be
Fungal pneumonias are a rare cause of respiratory failure among considered in HIV-infected individuals who have history of exposure
to endemic areas and who present with a compatible illness. Clinical
HIV-infected individuals. Disseminated infection is often present. features are nonspecific and may include fevers, dyspnea, focal or
Aspergillosis, cryptococcosis, histoplasmosis, and coccidioidomy- diffuse pulmonary infiltrates, meningitis, skin lesions, arthritis, and
cosis are encountered most frequently and usually are associated lymphadenopathy. Some patients have fevers and weight loss with no
with advanced HIV disease. Reported rarely in AIDS prior to 1990, focal lesions. The most common clinical presentations include diffuse
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invasive aspergillosis had an incidence estimated to be between 0.9% or focal pulmonary infiltrates and meningitis. The diagnosis is made
and 8.6% among patients with AIDS in the pre-ART era, but much by histologic examination and fungal culture of respiratory secretions,
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less common in recent years. Respiratory tract syndromes caused by tissue biopsies (skin or lymph node), spinal fluid, and blood. The char-
Aspergillus spp in AIDS include invasive pulmonary aspergillosis, acteristic coccidioidal spherules may be identified using lactophenol
obstructing bronchial lesions, and tracheobronchitis. The presenting cotton blue stain, Gomori silver methenamine stain, or Papanicolaou
symptoms frequently are cough and fever; less common complaints stain. The CSF characteristics in coccidioidal meningitis usually include
include dyspnea, chest pain, and hemoptysis. A common radiologic a pleocytosis of greater than 50 cells/µL that consists of predominantly
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finding in AIDS-related invasive pulmonary aspergillosis is a thick- lymphocytes. The CSF glucose concentration is low, and the protein
walled cavity. 116 concentration is elevated. Serology for coccidioidomycosis is positive in
■ HISTOPLASMOSIS approximately 80% of HIV-related cases, but seronegative pulmonary
disease has been described. Positive CSF serology (complement fixa-
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In North America, histoplasmosis is usually restricted geographically tion) for C immitis usually indicates the presence of coccidioidal men-
to the endemic zone extending from Mexico and Texas up through the ingitis. Fluconazole represents an important advance in the therapy of
central United States (especially the Mississippi Valley area) and into coccidioidomycosis because of the efficacy and lower side-effect profile
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eastern Canada. Most patients with histoplasmosis will have a history of fluconazole compared with amphotericin B. Lifelong suppressive
of exposure to endemic areas. 117-119 Although less common at present, azole therapy is required in coccidioidal meningitis. 131-133
to 5% of HIV-infected patients in endemic areas but in as many as 25% ■ KAPOSI SARCOMA
during the pre-ART era (before 1996), histoplasmosis occurred in 2%
in certain cities. Although over 90% of cases have occurred in patients Kaposi sarcoma (KS) involves the lungs in up to 15% of patients with
whose CD4 count was less than 100 cells/µL, histoplasmosis was the first mucocutaneous KS. Clinically significant pulmonary KS without
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AIDS-defining illness in half the cases. 120 obvious mucocutaneous involvement is rare. Pulmonary KS often is
Histoplasmosis in the context of AIDS is almost always a disseminated indistinguishable from other HIV-related pulmonary diseases. Cough
infection. The clinical presentation is usually that of a nonspecific febrile and dyspnea are common presenting features. Fever, wheezing, hoarse-
illness often accompanied by other features such as pulmonary infil- ness, and even upper airway obstruction can occur. Sputum production
trates, hepatosplenomegaly, lymphadenopathy, pancytopenia, and liver usually is scant or absent. Hemoptysis is relatively frequent. Chest radio-
enzyme elevations. The spectrum of disease ranges from a nonspecific graph usually shows nodular opacities of varying sizes coexisting with
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febrile illness (often with constitutional and/or respiratory symptoms) varying degrees of interstitial disease. Pleural and nodal involvement
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