Treatment of fungal meningitis with miconazole.

Twelve patients with fungal meningitis (ten cases were due to Coccidioides immitis, two were from Cryptococcus neoformans) were treated with brief courses of intravenous (IV) miconazole. Eleven patients, including patients with severe, chronic disease, had been treated unsuccessfully with amphotericin B. Four patients also received miconazole injected directly into the CSF. The drug was well tolerated by any route, with mild reversible side effects. After IV administration the miconazole concentration in the CSF rarely exceeded the minimal inhibitory concentration (MIC) of the infecting organism. Intra-CSF administration of 20 mg generally produced levels above the MIC for 24 hours. Five of ten patients with coccidiodial meningitis responded clinically. Of these five, four received only IV miconazole; three relapsed after therapy was stopped. Miconazole appears promising as a treatment of fungal meningitis, but trials of longer duration might prevent relapse.

Pseudomonas maltophilia causing heroin-associated infective endocarditis.

The association of Pseudomonas maltophilia endocarditis in three patients with recent history of intravenous drug abuse is reported. All three patients had abnormal heart valves (two prosthetic and one rheumatic). A prominent characteristic of this uncommon pathogen is its in vitro resistance to the commonly used antimicrobials. Cure was achieved in all three cases. In two cases, synergistic antibiotic combinations were used. In one case, plasmid-mediated resistance to amikacin sulfate (Amikan, British; no comparable US product) emerged during therapy. The two patients with prosthetic valves received combined surgical and antibiotic therapy.

Prevalence of measles antibodies in adults with HIV infection: possible risk factors of measles seronegativity.

OBJECTIVES: To determine the prevalence of measles (rubeola) immunity in a group of HIV-1-infected adults and to examine predictors of measles seronegativity in this population. SETTING: County hospital outpatient clinic and public-health department early HIV intervention clinic. PATIENTS: A total of 262 HIV-infected adults presenting to outpatient clinics between September 1990 and January 1991. INTERVENTIONS: Patients were screened for the presence of measles immunoglobulin G antibody, as measured by an enzyme-linked immunosorbent assay (ELISA). Pertinent clinical and immunologic information was recorded. Univariate and multivariate analyses were performed to identify possible risk factors for measles seronegativity. MAIN OUTCOME MEASURE: Measles seronegativity, as defined by a lack of detectable antibody (ELISA predicted index value < 1.0). RESULTS: Thirteen (5%) patients lacked serologic evidence of immunity. Risk factors for measles seronegativity included year of birth in 1957 or later, Caucasian (non-Hispanic) race and oral hairy leukoplakia. Factors associated with progressive HIV disease (other than hairy leukoplakia) were not associated with a lack of existing immunity. CONCLUSIONS: A high prevalence (95%) of measles antibody was found in this large group of HIV-infected adults. Young, white individuals born in 1957 or later were at the greatest risk for measles seronegativity, but declining immunity due to progressive HIV infection did not appear to be associated with a lack of antibody. Self-reported histories of measles infection or immunization were not reliable predictors of measles immunity.

Low-dose dapsone prophylaxis of Pneumocystis carinii pneumonia in AIDS and AIDS-related complex.

The efficacy, toxicity and cost of orally administered dapsone (50-100 mg/day) for prophylaxis of Pneumocystis carinii pneumonia (PCP) were evaluated in 30 patients with AIDS or AIDS-related complex (ARC). Six patients received primary and 24 secondary prophylaxis. Ten patients received a maximum dose of 100 mg/day and 20 a maximum of 50 mg/day for a median duration of 19 weeks; 22 of the 30 patients continue to receive prophylaxis as of May 1989. Four patients have died, none of pneumocystis infection. One patient with AIDS suffered a mild relapse while receiving 50 mg/day. Hematologic toxicity was mild and could not be definitively attributed to dapsone therapy; rash due to dapsone was documented in two patients. A review of 33 patients at our institution with a history of PCP who received no prophylaxis demonstrated seven relapses, three of which were fatal. Cost analysis revealed a significant advantage for oral dapsone over aerosolized pentamidine.

Coccidioidomycosis in compromised hosts. Experience at Stanford University Hospital.

To determine the frequency and clinical characteristics of infection with Coccidioides immitis in immunosuppressed patients at Stanford University Hospital, clinical records of 14 years were examined. Thirteen cases met the diagnostic criteria. Half had Hodgkin's disease. In six the infection was disseminated; five of the six died early in the course of their infectious illness, frequently without diagnosis. Conclusions include: 1. The occurrence of coccidioidomycosis in immunosuppressed patients seen at institutions in or adjacent to the endemic area is not as rare as the literature suggests. 2. Dissemination is frequently explosive and the radiographic appearance of pulmonary involvement may appear late. Widespread pulmonary dissemination may occur within 24 hours after a negative x-ray. 3. Although the skin test loses its diagnostic value, the serology remains valid. Thus immunosuppressed patients with febrile illnesses (with or without radiographically evident pulmonary involvement) who have a history of travel to an endemic area should have serological examinations. 4. Lymphocytopenia correlates with risk of dissemination of coccidioidomycosis. 5. The administration of immunsuppressive chemotherapy correlates with such risk while radiotherapy and the malignant or non-malignant nature of the disease do not.

Necrotizing or cavitating pneumonia due to Streptococcus Pneumoniae: report of four cases and review of the literature.

Streptococcus pneumoniae is seldom considered as an etiologic agent of necrotizing or cavitating pneumonia. However, during a 5-month period we encountered four patients, bacteremic with S. pneumoniae, with such a pulmonary process. Review of the older literature indicates that this association may be more frequent than is commonly assumed. Anatomic, physiologic, and immunologic alterations of the pulmonary defense mechanisms prior to and during the infection as well as virulence factors of S. pneumoniae (i.e., rapid multiplication, accumulation of capsular polysaccharides, and inhibition of phagocytosis) in concert may produce the resultant decrease in bacterial clearance from the lung with the consequent necrosis of lung parenchyma. Since sputum and blood cultures are reported to be positive in only 50 percent and 25 percent, respectively, of cases of pneumonia, etiologic diagnosis may be difficult. Nevertheless, S. pneumoniae must be considered in the differential diagnosis of the patient with necrotizing or cavitating pneumonia.

CD20 expression is increased on B lymphocytes from HIV-infected individuals.

In studies presented here, we show that expression of the pan B cell marker CD20 is markedly increased on B lymphocytes from HIV-infected individuals and that this increase tends to be greater in individuals with more advanced disease. By using multiparameter FACS analyses to quantitate surface density of CD20 and intracellular glutathione (GSH) levels simultaneously, we further show that the distribution of intracellular glutathione (GSH) levels in B cells of HIV-infected individuals is more heterogeneous than in uninfected controls. Finally, we show that the intracellular GSH levels correlate with CD20 expression on a per-cell basis in all infected individuals. These findings suggest that CD20 expression, which can be precisely measured, may prove to be a useful surrogate marker for monitoring HIV infection.

Early identification of neutropenic patients at risk of grampositive bacteraemia and the impact of empirical administration of vancomycin.

The aim of this multicentre randomised trial was to determine whether it was possible to predict grampositive bacteraemia, and whether the empirical use of vancomycin would lead to reduced morbidity and mortality. 35 of 113 patients (31%; confidence interval, CI 8.5), who presented with a skin or soft tissue infection and had received empirical vancomycin in addition to either ceftazidime or piperacillin-tobramycin, had initial bacteraemia with a single gram-positive bacterium compared with 135 of the 784 (17%; CI 2.6), who presented with another infection and who had been given ceftazidime or piperacillin-tobramycin without vancomycin (P < 0.001). Empirical vancomycin resulted in a higher rate of eradication (P = 0.033, relative risk 1.2), but not a better clinical outcome and was associated with more toxicity (P = 0.042, relative risk 1.6). Irrespective of the initial treatment regimen, fever lasted an average of 8 days, the empirical regimen was modified in more than 50% of cases and mortality attributed to gram-positive infection was less than 2%. Incorporating vancomycin in the initial empirical antibiotic regimen for febrile neutropenic patients does not appear necessary, even for skin and soft tissue infections associated with gram-positive bacteraemia.

Miconazole in coccidiodomycosis. II. Therapeutic and pharmacologic studies in man.

Fourteen patients with chronic coccidioidomycosis, many of whom had complicating concurrent diseases and/or had failed to respond to amphotericin therapy, were treated with intravenous miconazole, a synthetic imidazole drug previously shown to be effective in experimental murine coccidioidomycosis. Up to 3.6 g/day was given for up to three months. 7inimal inhibitory concentrations of mycelial and endospore phases of all clinical isolates of C. immitis were less than 2.0 mug/ml. Peak concentrations in the blood of up to 7.5 mug/ml (by assay against C. immitis in vitro) were achieved. Doses above 9 mg/kg or 350 mg/m2 were more efficacious in producing blood levels over 1 mug/ml. Serum protein binding, determined by several methods, was approximately 90 per cent. The disappearance of bioactive drug from blood after infusion has a rapid initial phase (t1/2 approximately 30 minutes) and a final plateau (t1/2 approximately 20 hours). Eight patients had objective evidence of response, three had slight or equivocal responses, two could not be evaluated, and one was a treatment failure. Side effects were generally uncommon, minor and transient except for phlebitis. Infusion into central venous catheters appears to circumvent this problem. Miconazole is a potentially useful drug in the treatment of coccidioidomycosis.

Visceral bacillary epithelioid angiomatosis: possible manifestations of disseminated cat scratch disease in the immunocompromised host: a report of two cases.

Opportunistic infection with the causative agent of cat scratch disease may be responsible for an unusual vascular proliferative lesion, referred to as bacillary epithelioid angiomatosis, previously described only in human immunodeficiency virus (HIV)-infected patients. We present a case of an HIV-infected patient with bacillary epithelioid angiomatosis involving the liver and bone marrow causing progressive hepatic failure. We also report a case of a cardiac transplant recipient with hepatic and splenic bacillary epithelioid angiomatosis manifesting as a fever of unknown origin, a previously unreported event in a non-HIV-infected patient. These cases represent the first documentation of bacillary epithelioid angiomatosis with visualization of cat scratch-like organisms involving internal organs.

Inflammatory pseudotumor of intra-abdominal lymph nodes manifesting as recurrent fever of unknown origin: a case report.

A 27-year-old man presented with a 7-month history of debilitating recurrent fever and weight loss. Extensive clinical evaluation led to the discovery of splenomegaly and retroperitoneal lymphadenopathy. The patient underwent splenectomy as well as liver and lymph node biopsy. Histologic examination of the lymph nodes, but not the liver and spleen, revealed inflammatory pseudotumor of lymph nodes. The patient has remained asymptomatic for more than 3 years following the surgical procedure despite the absence of further intervention. Inflammatory pseudotumor of lymph nodes should be considered in the differential evaluation of prolonged or relapsing fever of unknown etiology.

Intracellular glutathione levels in T cell subsets decrease in HIV-infected individuals.

The authors have shown previously that intracellular glutathione (GSH) plays an important role in the regulation of human immunodeficiency virus (HIV) transcription and replication in vitro, through modulation of signal transduction by inflammatory cytokines. Moreover, intracellular GSH levels are known to regulate T-lymphocyte function. In multiparameter FACS studies presented here, we show that relative GSH levels in CD4+ and CD8+ T cells from HIV+ individuals are significantly lower than in corresponding subsets from uninfected controls. These studies define the relative intracellular glutathione (GSH) levels in CD4+ T cells, CD8+ T cells, B cells, and monocytes from 134 HIV-infected individuals and 31 uninfected controls. The greatest decreases in intracellular GSH occur in subsets of T cells in individuals in the later stages of the HIV infection. In AIDS patients, GSH levels are 63% of normal in CD4+ T cells (p less than 0.0001) and are 62% of normal in CD8+ T cells (p less than 0.0001). Similarly, in AIDS-related complex (ARC) patients, GSH levels are 66% of normal in CD4+ T cells (p less than 0.003) and are 69% of normal in CD8+ T cells (p less than 0.003). These findings suggest that low intracellular GSH levels may be an important factor in HIV infection and in the resulting immunodeficiency.

Azithromycin prophylaxis during a hospitalwide outbreak of a pertussis-like illness.

A questionnaire regarding tolerability and adherence was administered for 5 days to hospital employees who received azithromycin prophylaxis during a hospitalwide outbreak of a pertussis-like illness. Analysis of the 239 responses from those having received prophylactic azithromycin determined that it was well tolerated and accounted for a minimal loss of days worked; 81.5% were fully adherent with the regimen.

Hyperimmune products in the prevention and therapy of infectious disease: a report of a hyperimmune products expert advisory panel.

This paper reviews a meeting at which basic pathophysiology of infections, mechanisms of action of hyperimmune products and pharmacokinetic and pharmacodynamic parameters, as well as currently available hyperimmunes and their potential new targets and uses, were discussed. A hyperimmune product was defined as either a monoclonal antibody or a polyclonal preparation enriched with antibody directed against one or more particular targets. A number of issues were emphasised, including: resistant bacterial pathogens, such as Staphylococcus aureus and Streptococcus pyogenes; the role of hyperimmune intravenous globulins in the prevention of sepsis in low birthweight infants; hepatitis B virus infection associated with liver transplantation; combination therapy; the potential role of hyperimmunes in the prevention and treatment of hepatitis C virus; and the use of immunoglobulins for the prophylaxis of Epstein-Barr virus-related lymphoproliferative disease. Routes of administration were also discussed. It was concluded that the development of hyperimmunes faces numerous obstacles. It was agreed that the use of hyperimmunes in clinical trials must be standardised; clinical trials must be large enough to have sufficient power to demonstrate efficacy with clear-cut end-points, and means need to be developed, in conjunction with regulatory agencies, for the feasible evaluation of combination products. However, progress in all these aspects will provide a wide range of hyperimmunes for future use.

Flubendazole and mebendazole in the treatment of trichuriasis and other helminthiases.

Forty patients were treated with either flubendazole or mebendazole, 100 mg twice a day for three days, in a double-blind, prospective, randomized study. The study concentrated on patients with Trichuris trichiura infections, although the effects of the anthelmintic agents on concomitant Ascaris lumbricoides and hookworm infections were also evaluated. Results from 35 evaluable patients showed complete cure in 17/19 (89%) patients treated with flubendazole and 15/16 (94%) patients treated with mebendazole (P less than 0.05, no significant difference). Significant reduction in Trichuris egg counts was noted in the three other patients. No significant adverse clinical or laboratory reactions were noted. Other roundworms were completely eradicated by both anthelmintic agents. Based on this study, flubendazole appears to be as effective and safe as mebendazole in the treatment of nematode infections.

Diagnosis and management of pneumonia.

The management of patients with pneumonia, the fifth leading cause of death in the United States, remains frequently problematical. Because a precise etiologic diagnosis is often not possible when the patient is first examined, initial antibiotic therapy is often empiric. Problems in early diagnosis include the frequent lack of access to true respiratory secretions, necessary delays in identification of organisms in culture, and contamination of expectorated sputum with oropharyngeal bacteria. Early management must therefore depend on epidemiologic and clinical clues as well as examination of available respiratory secretions. It is generally helpful in the selection of initial antibiotic therapy to consider the disease in two broad epidemiologic categories, community- and nosocomially acquired. As new laboratory and clinical information become available, the appropriateness of the antibiotic therapy must be continually reevaluated.

Helicobacter (Campylobacter) fennelliae-like organisms as an important but occult cause of bacteraemia in a patient with AIDS.

We describe the isolation and identification of a Helicobacter (Campylobacter)-like organism obtained from the blood of a 32-year-old homosexual man with a 10 months' history of AIDS and progressive mucocutaneous Kaposi sarcoma. Fever and bacteremia persisted despite sequential administration of ciprofloxacin and trimethoprim-sulfamethoxazole, antibiotics reported to be active against this organism in vitro. Facultative organisms like Campylobacter fennelliae and Campylobacter cinaedi which are difficult to isolate by standard techniques may be important but unrecognized causes of febrile illness in patients with human immunodeficiency virus infection. Laboratories should consider use of acridine orange staining and more extensive subculture protocols for blood cultures with progressive growth indices which appear negative by conventional staining and subculture technique.

Travels with HIV: the compliance and health of HIV-infected adults who travel.

We examined the effects of travel on the health of a group of HIV-infected adults (n = 89) cared for in a public hospital HIV clinic. In a period of 2 years, 45% travelled to a median of 3 US destinations for at least one week and 20% travelled to at least one international destination for a mean duration of 20 days. At the time of completion of the survey, the majority of these patients were severely immunosuppressed (median CD4+ count, 120/mm3). A physician was consulted concerning travel before 53% of the trips, but only one person consulted a travel medicine expert. All but one patient (98%) who was receiving medical therapy carried sufficient supplies of medication; 95% estimated their compliance with medication at 75% or better. None of the travellers to developing countries received gamma globulin, but one received yellow fever vaccine. Fifteen travellers (43%) became ill either during their trip or immediately thereafter; 3 required hospitalization. While most illnesses were not severe, 4 patients developed potentially life-threatening infections including coccidioidomycosis, cryptococcosis, PCP, and bacterial pneumonia. This survey provides information by which the clinician can anticipate the health care needs of HIV-infected patients who travel. HIV-infected patients should be more aware of the necessity for medical counsel prior to travel.

Case report. Fatal gas gangrene following intra-articular steroid injection.

Gas gangrene is a rare infectious disease syndrome complicating medico-surgical procedures. We describe a case of gas gangrene secondary to intra-articular steroid injection. Clostridia species and Escherichia coli were the etiologic organisms in this case. The presence of underlying diseases such as diabetes mellitus, hepatic insufficiency, and metabolic acidosis could have contributed to the fatal outcome of this patient. A high index of suspicion, early diagnosis, and appropriate treatment may improve the prognosis in gas gangrene. Although uncommon, infection is a significant complication of intra-articular steroid administration. Thus, meticulous aseptic technique should always be observed in the performance of this procedure.