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In a case-control study to identify risk factors for fluconazole-resistant oroesophageal candidiasis in human immunodeficiency virus-infected patients, 25 patients with clinical and in vitro fluconazole-resistant candidiasis were paired with controls who had treatment-responsive candidiasis and who had been observed for similar time periods. After their first episode of candidiasis, patients who later developed fluconazole resistance had more treated episodes than did matched controls (cases, 3.1; controls, 1.8; P = .004), lower median CD4 cell counts (11/mm3 vs. 71/mm/3; P = .004), and greater median durations of all antifungal therapy (419 vs. 118 days; P < .001) and of systemic azole therapy (272 vs. 14 days; P < .001). When paired with a second set of controls matched by CD4 cell count as well as first diagnosis of candidiasis, cases continued to show greater median exposure to azoles (272 vs. 88 days; P = .005). These data indicate that advanced immunosuppression and exposure to oral azoles are risk factors for the development of fluconazole resistance. [ABSTRACT FROM AUTHOR]

In an examination of the relationships among plasma aminoglycoside concentrations, the minimal inhibitory concentration (MIC) for the infecting organism, and therapeutic outcome, data were analyzed from 236 patients with gram-negative bacterial infections who were participants in four clinical trials of gentamicin, tobramycin, and amikacin. Clinical response to therapy occurred in 188 (80%) patients. Elevated maximal and mean peak aminoglycoside concentration/MIC ratios were strongly associated with clinical response (P less than .00001 and P less than .0001, respectively). A graded dose-response effect was found between an increasing maximal peak concentration/MIC ratio and clinical response. By logistic regression the peak concentration/MIC ratios were associated significantly with clinical response after adjustment for underlying severity of illness and other factors correlated with response. These results demonstrate that a high peak concentration relative to the MIC for the infecting organism is a major determinant of the clinical response to aminoglycoside therapy. [ABSTRACT FROM AUTHOR]

Risk factors for the development of auditory toxicity in patients receiving aminoglycosides were determined from the analysis of 135 patients enrolled in three prospective, randomized, double-blind clinical trials of gentamicin, tobramycin, and amikacin. Auditory toxicity, defined as a decrease in auditory acuity of greater than or equal to 15 dB, occurred in 30 patients (22.3%). Patients with auditory toxicity underwent therapy for a longer period, were more likely to be bacteremic, and had, on the average, a higher temperature (P less than 0.05). Using stepwise discriminant analysis, we selected these factors with liver dysfunction and the serum urea nitrogen:serum creatinine ratio in a function that accurately discriminates between toxic and nontoxic patients. Factors not adding significantly to the predictive accuracy of the equation were plasma aminoglycoside levels, aminoglycoside type, furosemide use, diabetes, age, sex, renal function, initial auditory acuity, hematocrit value, and shock. This analysis may be important both for determining the pathophysiology of auditory toxicity and for the prognostic stratification of patients receiving aminoglycosides in clinical trials. [ABSTRACT FROM AUTHOR]

In many patients, the etiology of community-acquired pneumonia is not known but may be caused by previously undescribed pathogens in some cases. The recently identified hantavirus Sin Nombre (SN) causes hantavirus pulmonary syndrome. Because sporadic cases have occurred outside the range of its reservoir (the deer mouse Peromyscus maniculatus), an investigation sought to determine whether hantaviruses contributed to cases of community-acquired pneumonia in a large Baltimore hospital. Acute-phase sera from 385 hospitalized patients with pneumonia were examined using an IgG ELISA technique with antigens prepared from several hantaviruses: prototype Hantaan (HTN), Seoul (SEO), Puumala (PUU), Convict Creek (HN107), and SN. Of 385 sera, 8 (2.1%) showed some reactivity with one or more HTN, SEO, or PUU antigens but none had detectable specific IgM antibodies. No sera were reactive with SN or HN107 antigens. Thus, hantaviruses are an uncommon cause of community-acquired pneumonia in the Baltimore area. [ABSTRACT FROM AUTHOR]

The effect of acute coinfections on plasma human immunodeficiency virus (HIV) load and immune activation markers was evaluated. Thirty-two HIV-infected persons were prospectively enrolled; 18 had pre-illness, acute, and follow-up specimens. Plasma HIV RNA levels were determined by reverse transcriptase-polymerase chain reaction, and serum levels of activation markers, including tumor necrosis factor (TNF)-alpha, soluble (s) TNF receptors (R)-I and -II, interleukin (IL)-2, IL-6, IL-10, sIL-2R, sCD4, and sCD8, were assessed by commercial ELISAs. Median plasma HIV load increased 7. 8-fold during illness (P=.001) and decreased 1.5-fold (P=.01) during convalescence (median, 15 days). Significant virus load reductions were limited to subjects with clinical recovery. By regression analysis, changes in plasma HIV RNA were significantly associated with changes in sTNFR-I, sTNFR-II, and sIL-2R. Increased HIV replication during acute coinfections is associated with in vivo immune activation, which underscores the need to prevent and promptly treat intercurrent illnesses.

To evaluate the impact of Cryptosporidium infection on diarrheal disease burden and nutrition status, a nested case-control study was done among children who were followed from birth in Fortaleza, Brazil. The diarrhea history and growth records of 43 children with a symptomatic diarrhea episode of cryptosporidiosis (case-children) were compared with those of 43 age-matched controls with no history of cryptosporidiosis. After Cryptosporidium infection, case-children < or = 1 year old experienced an excessive and protracted (nearly 2 years) diarrheal disease burden. Case-children < or = 1 year old with no history of diarrhea prior to their Cryptosporidium infection also experienced a subsequent increased diarrheal disease burden with an associated decline in growth. Control subjects experienced no change in their diarrhea burden over time. This study suggests that an episode of symptomatic Cryptosporidium infection in children < or = 1 year of age is a marker for increased diarrhea morbidity.

To evaluate the association between acyclovir use and survival in patients with advanced human immunodeficiency virus infection, observational data from 1044 persons with AIDS or AIDS-related complex (ARC) and < or = 250 CD4 cells/mm3 following initiation of zidovudine were analyzed. Of these patients, 336 (32%) received regular acyclovir (> or = 6 weeks in 2 months). There were no differences in mortality data between acyclovir users and nonusers overall or when analyzed from 1 year after first use of zidovudine, from time of AIDS in those with ARC at enrollment, from patients with AIDS or < 100 CD4 cells/mm3 at enrollment, or from patients taking acyclovir for up to 10 months. Acyclovir use was associated with increased mortality (relative hazard, 1.28; P = .057) independent of herpesvirus infections and of other characteristics associated with mortality. In this study, the use of acyclovir at doses for treatment of herpes simplex virus infection in combination with zidovudine was not associated with prolonged survival.

To determine the prevalence, incidence, and effects on disease progression and survival of herpes zoster in patients with advanced human immunodeficiency virus (HIV) disease, data from a multicenter observational cohort study of 1044 patients with AIDS or AIDS-related complex (ARC) and CD4 cell count < or = 0.25 x 10(9)/L treated with zidovudine were analyzed. Of 163 patients (16%) with a history of herpes zoster at enrollment, 22 (13%) had a recurrence during the 2-year follow-up. For those without prior herpes zoster, the probability of its development was 6.3% at 1 and 8.8% at 2 years. Progression to AIDS was not associated with herpes zoster. By proportional hazards analysis, an initial occurrence of herpes zoster was associated with prolonged survival independent of baseline CD4 cell count and disease stage; however, recurrence tended to be associated with death. Thus, herpes zoster is relatively common in advanced HIV infection and its initial occurrence late in disease may indicate improved prognosis.

Data were analyzed from a multicenter observational cohort study of 1002 persons with AIDS or AIDS-related complex (ARC) and total CD4 cell count < 0.25 x 10(9)/L treated with zidovudine between April 1987 and April 1988. Cytomegalovirus (CMV) disease developed in 109 patients (10.9%), with a 2-year actuarial risk of 15%. Manifestations included retinitis (93 patients), esophagitis (10), colitis (8), gastritis (1), hepatitis (1), and encephalitis (1). The probability of CMV disease at 2 years for patients with initial counts < 0.1 x 10(9)/L was 21.4%, compared with 10.3% for patients with initial counts > or = 0.1 x 10(9)/L (P < .001). By proportional hazards analysis, baseline CD4 cell count < 0.1 x 10(9)/L, enrollment diagnosis of AIDS, and homosexuality were significantly associated with subsequently developing CMV disease. Median survival after diagnosis of CMV disease was 173 days, and CMV was an independent predictor of death. CMV contributes to AIDS-related morbidity and mortality. As new anti-CMV drugs become available, prophylaxis should be targeted at individuals with CD4 cell counts < 0.1 x 10(9)/L.