Bacteremia and fungemia in patients with the acquired immunodeficiency syndrome

Forty-nine episodes of bacteremia and fungemia occurred in 38 of 336 patients with the acquired immunodeficiency syndrome seen at our institution since 1980. There were five types of infections. Infections commonly associated with a T-cell immunodeficiency disorder comprised 16 episodes and included those with Salmonella species, Listeria monocytogenes, Cryptococcus neoformans, and Histoplasma capsulatum. Infections commonly associated with a B-cell immunodeficiency disorder included those with Streptococcus pneumoniae and Haemophilus influenzae. Infections occurring with neutropenia were caused by Pseudomonas aeruginosa, Staphylococcus epidermidis, and Streptococcus faecalis. Other infections occurring in the hospital were caused by Candida albicans, Staphylococcus epidermidis, enteric gram-negative rods, Staphylococcus aureus, and mixed S. aureus and group G streptococcus. Other infections occurring out of the hospital included those with S. aureus, Clostridium perfringens, Shigella sonnei, Pseudomonas aeruginosa, and group B streptococcus. Because two thirds of the septicemias were caused by organisms other than T-cell opportunists, these pathogens should be anticipated during diagnostic evaluation and when formulating empiric therapy.     

Bacteremia due to Mycobacterium avium-intracellulare in the acquired immunodeficiency syndrome

The presence of Mycobacterium avium-intracellulare has frequently been demonstrated in tissue specimens from patients with the acquired immunodeficiency syndrome. The importance of this mycobacterium as a cause of constitutional symptoms and organ dysfunction has been unclear, however, because of the sparse inflammatory response evoked and the frequent concurrence of other pathogenic organisms. We detected M. avium-intracellulare in blood samples from eight patients with the acquired immunodeficiency syndrome, seven of whom had a previously recognized M. avium-intracellulare infection. Blood cultures were positive on 1 to 14 occasions over 135 days using the Dupont isolator system or the Bactec 12B medium system. Cultures were positive within 14 to 51 or 7 to 14 days with the respective techniques. The ability to rapidly isolate M. avium-intracellulare from blood may provide a useful diagnostic technique for detecting disseminated mycobacterial disease in patients with the acquired immunodeficiency syndrome as well as in other patient populations. This technique may also be useful for assessing the efficacy of drug therapy.     

Blastomycosis in patients with the acquired immunodeficiency syndrome.

OBJECTIVE: To describe the clinical, demographic, radiographic, diagnostic, and therapeutic aspects of blastomycosis in patients with the acquired immunodeficiency syndrome (AIDS). DESIGN: A retrospective survey. SETTING: Ten university medical centers and community hospitals, six in geographic areas endemic for Blastomyces dermatitidis, and four outside the endemic area. PATIENTS: We identified 15 patients with blastomycosis and positive serologic test results for human immunodeficiency virus (HIV). MEASUREMENTS: A diagnosis of blastomycosis was based on a positive culture (14 patients) or typical histopathologic features (one patient) for B. dermatitidis in clinical specimens. RESULTS: Twelve of 15 patients had a previous or concomitant AIDS-defining illness at the time of diagnosis of blastomycosis, and only one patient had a CD4 lymphocyte count of greater than 200 cells/mm3. Two patterns of disease emerged: localized pulmonary involvement (seven patients), and disseminated or extrapulmonary blastomycosis (eight patients). Central nervous system involvement was common (40%). Six patients died within 21 days of presentation with blastomycosis, including four patients with disseminated and two with fulminant pulmonary disease. Among the nine patients who survived longer than 1 month, all received amphotericin B as initial antifungal therapy, and most received subsequent therapy with ketoconazole. Only two of these nine patients died with evidence of progressive blastomycosis. CONCLUSIONS: Blastomycosis is a late and frequently fatal infectious complication in a few patients with AIDS. In these patients, overwhelming disseminated disease including involvement of the central nervous system is common, and it is associated with a high early mortality. Initial therapy with amphotericin B is appropriate in patients with AIDS and presumptive blastomycosis.     

Toxoplasma encephalitis in patients with the acquired immunodeficiency syndrome.

Among 504 cases of AIDS diagnosed between 1983 and 1990, there were 86 patients (17%) with toxoplasma encephalitis (TE). All were symptomatic at the time of diagnosis. General signs such as fever, neck stiffness, or headache were present in 87.2%, and 75.6% had focal signs. The primary means of diagnosis was computerized tomographic scanning, revealing 169 lesions of which 80% were immediately contrast-enhancing. All patients had IgG antibodies against Toxoplasma gondii either before (74 of 75 evaluable patients) or at the time of diagnosis of TE (73 of 75). Elevated antibody titers were present in 44% of evaluable patients, compared to 11% of patients with AIDS and other opportunistic infections. Initial treatment was pyrimethamine plus sulfonamides in 65 patients, and pyrimethamine plus clindamycin in 12 patients, with other combinations or no treatment accounting for the remainder. Life-table analysis of the time to discontinuation of treatment because of suspected side effects suggested that sulfadiazine was significantly more toxic, with 48% of patients experiencing an interruption in treatment after 30 days, than pyrimethamine (12%) or clindamycin (24%). The 30-day mortality rate was 12%, and median survival was 310 days after diagnosis, 530 in patients treated with zidovudine and 190 days in those not so treated. Of 82 evaluable patients, 16 relapsed once and 4 of these more than once. The risk of relapse was 27% 1 year after diagnosis of a first episode of TE.     

Effects of passive immunization in patients with the acquired immunodeficiency syndrome-related complex and acquired immunodeficiency syndrome.

Infection with the human immunodeficiency virus type 1 (HIV-1) is usually followed by a vigorous immune response that temporarily protects against disease progression. After a variable asymptomatic period, acquired immunodeficiency syndrome (AIDS)-related complex (ARC) and AIDS develop in most infected individuals. We have demonstrated that healthy HIV-1-infected individuals have neutralizing antibodies and a high titer of antiviral antibodies. In contrast, AIDS patients have undetectable levels of neutralizing antibodies, low titers of antiviral antibodies, and, frequently, HIV p24 antigenemia. These observations prompted us to attempt passive immunization in ARC and AIDS patients. Ten consistently viral-antigen-positive patients (mean, greater than 6 months) were treated, resulting in sustained clearance of p24 antigen. Patients either maintained or increased their antiviral antibody titers. The raised titers result from increased antibody synthesis by the recipients. Circulating CD4+ cell counts were unchanged after 2 months. By the third month none of these patients remained in hospital. As this treatment was of minimal toxicity, it merits wider evaluation in ARC and AIDS patients.     

Lipid-laden perisinusoidal cells in patients with acquired immunodeficiency syndrome.

Liver biopsies were taken from ten AIDS patients. Liver architecture was normal in all patients. On 1-micron-thick sections stained with toluidine blue, all ten cases showed lipid overload of perisinusoidal cells (1 massive, 5 moderate and 4 mild) compared to 2/8 in control patients, who had mild lipid overload. Other sinusoidal abnormalities such as hypertrophy of Kupffer cells and inclusions in endothelial cells were also noticed. Some hepatocytes presented evidence of cellular damage. Perisinusoidal cell lipid overload was not associated with hypervitaminosis A. We hypothesize that the abnormal accumulation of lipids in perisinusoidal cells (non-induced by hypervitaminosis A) in patients with AIDS could be due to defective transport of vitamin A from perisinusoidal cells to hepatocytes, and/or from hepatocytes to blood. The cause of the defect is unknown. Since lipid overload occurs in many and diverse conditions (diabetes, cholestasis, primary biliary cirrhosis, etc.), it seems reasonable to propose that the defect is non-specific and limited to functional or structural damage of the liver whether induced by drugs, liver or systemic diseases.     

Bacteremia and ecthyma caused by Streptococcus pyogenes in a patient with acquired immunodeficiency syndrome

Ecthyma is an ulcerated form of impetigo due to Streptococcus pyogenes, seen primarily in children with poor hygiene. The authors report a homosexual man with acquired immunodeficiency syndrome (AIDS) who developed severe ecthyma and bacteremia caused by S. pyogenes. Opsonizing antibody to the M protein of S. pyogenes is important in immunity to this organism. Patients with AIDS may have defective humoral immunity as well as defective cellular immunity, and such a defect may have rendered this patient abnormally susceptible to severe infection with S. pyogenes.     

Salmonella infections in patients with the acquired immunodeficiency syndrome

Defects in T-cell function have been seen in patients with the acquired immunodeficiency syndrome. Although the cellular immune system plays a key role in host defense against Salmonella, there have been no detailed reports of salmonellosis in patients with this syndrome. We report our experience with salmonella infections in six patients. Salmonellosis in these patients was unusually severe, characterized by widespread infection, bacteremia, and relapse, despite standard antibiotic treatment. Because of the difficulty in eradicating salmonella infection in patients with the acquired immunodeficiency syndrome, long-term suppressive treatment with antibiotics seems warranted.     

Prevalence of toxoplasma myocarditis in patients with the acquired immunodeficiency syndrome.

OBJECTIVE--To evaluate the prevalence of cardiac toxoplasmosis in a series of 182 necropsies performed between 1987 and 1991 on patients infected with the human immunodeficiency virus (HIV), to correlate this prevalence with the ante mortem diagnosis of cardiac involvement, and to assess the role of such cardiac lesions in the immediate cause of death. PATIENTS AND METHODS--Complete necropsies of 182 HIV-infected patients (48 women, 134 men) were performed consecutively between 1987 and 1991. Risk factors, identified in 174 cases, included drug abuse (111/182), homosexuality (51/182), and blood transfusions (12/182). 16 samples were systematically obtained from each heart for histological study. If trophozoites or lymphocytic myocarditis were seen, immunohistochemical investigations were carried out with polyclonal antibodies for Toxoplasma gondii. An ultrastructural study was performed in four patients with toxoplasma myocarditis. Myocardial lesions were defined by the Dallas classification. Clinical data (and information on electrocardiograms and echocardiograms) were obtained from medical records. RESULTS--Cardiac toxoplasmosis was diagnosed at necropsy in 21 (12%) patients. Cardiac lesions were associated with toxoplasmic encephalitis in 18 patients and were solitary in three patients. Acute diffuse myocarditis was present in 6/21, rare foci of myocarditis were seen in 8/21, and intramyocytic toxoplasmic cysts without any inflammatory reaction or necrosis were seen in 4/21. Anti-toxoplasma immunolabelling showed cardiac toxoplasmosis in three patients with lymphocytic myocarditis. Particles with the ultrastructural characteristics of Toxoplasma gondii trophozoites were seen in four cases. Six patients had presented with cardiac symptoms, confirmed by electrocardiographic and echocardiographic abnormalities during their disease course, and their cardiac lesions were directly responsible for the death. CONCLUSION--Cardiac toxoplasmosis was common in this necropsy series of HIV-infected patients. Cardiac toxoplasmosis had been suspected clinically in four patients. Myocardial lesions were generally asymptomatic and were not discovered until necropsy. Solitary cardiac involvement was not uncommon reflecting parasite reactivation at a myocardial site. The incidence of cardiac toxoplasmosis in this group of immunodepressed subjects from an area with a high prevalence of this parasitic disease justifies regular follow up of such patients by electrocardiography and echocardiography as well as immediate administration of anti-toxoplasma treatment should sudden heart failure occur.     

Septic arthritis in patients with acquired immunodeficiency syndrome with human immunodeficiency virus infection.

We have evaluated the presence and characteristics of septic arthritis in intravenous (iv) drug users with human immunodeficiency virus (HIV) infection. Sixteen patients with both HIV infection and septic arthritis were studied and compared with 5 patients with septic arthritis but no HIV infection. Clinical profile, laboratory findings at the time of onset, localization, causative organisms, mean hospitalization time and presence of complications were the same in HIV positive and HIV negative patients. Staphylococcus aureus was the most commonly isolated organism in both groups. We conclude that septic arthritis in HIV infected iv drug users is not uncommon, it is produced by the same organisms and presents similar characteristics to the ones found in iv drug users without HIV infection. Therefore, the presence of HIV infection does not appear to modify the characteristics of septic arthritis.     

High-protein ascites in patients with the acquired immunodeficiency syndrome

Diseases of the liver or peritoneum resulting in ascites have been infrequently reported in patients with the acquired immunodeficiency syndrome. Since 1985, eight noncirrhotic patients with the acquired immunodeficiency syndrome presenting with new onset high-protein ascites have been evaluated. All but one patient had nondiagnostic paracentesis studies. Laparoscopy with biopsy of identified abnormalities or percutaneous omental biopsy were diagnostic in four patients. Non-Hodgkin's lymphoma was the cause in three patients, and disseminated cryptococcosis occurred in one patient. In the four other patients, chronic nonspecific peritonitis was found at laparoscopy; follow-up of these latter patients, including exploratory laparotomy in one patient and autopsy in two patients, disclosed no specific cause. Patients with the acquired immunodeficiency syndrome and high-protein ascites of uncertain etiology should undergo directed peritoneal evaluation as a potentially treatable disorder may be found. However, despite extensive evaluation, a subset of patients in whom no specific cause can be identified still remains.     

Bacterial pneumonia in patients with the acquired immunodeficiency syndrome

Eighteen episodes of community-acquired bacterial pneumonia were diagnosed in 13 patients among 336 with the acquired immunodeficiency syndrome (AIDS) cared for at Memorial Sloan-Kettering Cancer Center since 1979. Bacterial pathogens isolated in 16 of 18 episodes were Haemophilus influenzae in 8, Streptococcus pneumoniae in 6, group B streptococcus in 1, and Branhamella catarrhalis in 1. Eight episodes were presumed Pneumocystis carinii pneumonia until cultures obtained at bronchoscopy confirmed a bacterial cause. Specific antibacterial therapy was curative in 16 of 18 episodes; 2 patients died. Given an estimated yearly incidence of pneumococcal pneumonia in the general population of 2.6/1000, 1.09 cases were expected in our patients with AIDS; we saw 6 (p = 0.001), for an attack rate of 17.9/1000. Bacteria associated with B-cell defects should be anticipated when formulating empiric antibiotic therapy, pending a definitive diagnosis, for pulmonary infiltrates in patients with AIDS.     

Intestinal infections in patients with acquired immunodeficiency syndrome

We studied prospectively 132 patients with acquired immunodeficiency syndrome to define the spectrum of enteric pathogens during this disease, with special reference to the correlation between the lesions, the infections, and the symptoms. Forty-four percent of the patients harbored at least one enteric pathogen: the most frequently recovered were Cryptosporidium (28), cytomegalovirus (16), Entamoeba histolytica (13), Giardia lamblia (9), and Mycobacterium avium intracellulare (7). Patients harboring pathogens were more likely to be diarrheics (69%) than patients without a pathogen (38%; P=0.01) and more likely to have endoscopic lesions (29%) than patients without a pathogen (4%; P<0.001). The most common pathogen associated with diarrhea was Cryptosporidium. Cytomegalovirus, Entamoeba histolytica, and Salmonella typhimurium were each significantly associated with endoscopic lesions. Patients with cytomegalovirus infection tended to have a greater incidence of ulcer than patients without cytomegalovirus infection. Stool analysis diagnosed 61% of the infections, while endoscopy diagnosed 44%. Seven percent were recognized by stool analysis and endoscopy. When considering the 24 patients in whom accurate diagnosis warranted endoscopic biopsies, stool examination alone would have given an incomplete diagnosis in 14 patients (due to the presence of polyinfection). The frequency of inaccurate diagnosis of infection by stool determination alone, plus the development of new antiviral agents that suppress cytomegalovirus, may favor the earlier application of endoscopic evaluation in these patients.Computerized treatment of data has been allowed by the Commission Nationale Informatique et Liberté (registration NB. 104713).This work was supported in part by Institut National de la Santé et de la Recherche Médicale, (grant UR/010/237) and by Fondation Médicale pour la Recherche, and by Paris VII Faculté.Portions of this study were presented at the American Gastroenterological Association in May 1987.     

Cytomegalovirus colitis in patients with acquired immunodeficiency syndrome

Twenty-four AIDS patients, who underwent gastrointestinal evaluation, died from their disease and were autopsied. Seven had Cytomegaloviruscolitis (group I) and 17 did not (group II). Clinical manifestations, digestive lesions, and infections were compared in the two groups. Chronic watery diarrhea was present in all the patients with colitis but was also present in 65% of the patients without colitis. Hematochezia was present only in the group with colitis (one of seven patients) but appeared late in the diarrheal course, due to necrotizing colitis. No other difference were noted between the two groups (mean duration of diarrhea, frequency and nature of the other infections). As for group I specifically,colonic ulcerations due to Cytomegaloviruswere present in all the patients, varying from punctate and superficial erosions to deep ulcerations, with granular and friable intervening mucosa. Severe colonic lesions appeared during the course of Cytomegaloviruscolitis in two patients who developed lethal necrotizing colitis. Finally, the clinical and pathologic features of these seven cases were compared to other reports of Cytomegalovirusinfection of the colon.     

Tuberculosis in non-Haitian patients with acquired immunodeficiency syndrome

From Jan 1, 1981 to Oct 31, 1984, 24 of 280 (8.6 percent) patients with acquired immunodeficiency syndrome (AIDS) had tuberculosis. No patient with both AIDS and tuberculosis was Haitian. In 15 patients, tuberculosis was diagnosed prior to or concomitant with the diagnosis of AIDS. Twelve patients (50 percent) had Mycobacterium tuberculosis grown from at least one extrapulmonary site. Although the clinical presentation was variable, no patient had cavitary and only one had apical disease. Histologic examination of lung and transbronchial biopsy specimens usually did not reveal acid-fast bacilli or granulomas. Seventeen patients were treated and all showed clinical improvement. Tuberculosis was infrequent but not rare in our patients and often preceded the diagnosis of AIDS. Despite the fact that many of these patients had both severe and extrapulmonary disease, they appeared to respond well to treatment.     

Pulmonary tuberculosis in patients with acquired immunodeficiency syndrome

An association between tuberculosis and HIV infection is becoming increasingly evident. HIV seropositivity has been seen in nearly 30% of some populations with tuberculosis. In other populations nearly 25% of patients with AIDS had tuberculosis. Clinically these patients present with nonspecific findings including weight loss, night sweats, and fever. The symptoms are generally gradual in onset and last for several weeks. Early in the course of HIV infection a PPD skin test may be positive and the radiographic findings may be similar to those seen in individuals with normal immunity. Thus, upper lobe heterogeneous and cavitary opacities may be seen on the chest radiograph. In late HIV infection, however, the PPD skin test is generally negative and the radiograph demonstrates lymphadenopathy and diffuse heterogeneous parenchymal opacities. Tuberculosis should be suspected in HIV-infected patients when diffuse interstitial lung disease is demonstrated in conjunction with hilar or mediastinal lymph node enlargement. In contrast, lymphadenopathy is not expected in the most common opportunistic lung disease, Pneumocystis carinii pneumonia. Standard antituberculous drug therapy is extremely effective in treating tuberculosis in this setting.     

Salmonella infections in patients with acquired immunodeficiency syndrome

Salmonella infections occurred in six patients with acquired immunodeficiency syndrome (AIDS) and one patient with probable AIDS. The immune system defects increase the susceptibility of patients with AIDS to salmonella infections. Recognition of salmonellosis in patients with AIDS is important because of a high propensity of this organism to invade the bloodstreams of these patients, and because, unlike other infections in patients with AIDS, this infection can be easily treated.