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R D Moore

Publications and source records attributed to R D Moore.

At least 91 records · Page 5Linked to original sources
PubMed1996

Risk factors for fluconazole-resistant candidiasis in human immunodeficiency virus-infected patients.

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.

AIDS-Related Opportunistic Infections↗
PubMed1996

Hantavirus serologies in patients hospitalized with community-acquired pneumonia.

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.

Adult↗
PubMed1996

Risk factors for pneumococcal disease in human immunodeficiency virus-infected patients.

To identify risk factors for pneumococcal infection among human immunodeficiency virus-infected patients, a nested case-control study was done in an urban university human immunodeficiency virus clinic. Subjects with pneumococcal illness seen between 1 January 1990 and 1 July 1994 (n=85) were randomly matched to controls from the same population. Patients with pneumococcal disease were more likely than controls to be African Americans (adjusted odds ratio [OR]=3.92), have <200 CD4 cells/mm3 (adjusted OR=3.38), have a history of any pneumonia (adjusted OR=3.28), and have an albumin level of <3.0 g/dL (adjusted OR=6.25). Use of zidovudine (adjusted OR=0.38) and pneumococcal vaccination when the subject had >200 CD4 cells/mm3 (adjusted OR=0.22) were less common in cases than in controls. Similar results were found when only cases with infections of usually sterile sites were analyzed. Pneumococcal vaccine may be most protective when it is administered before advanced immunodeficiency develops.

Adult↗
PubMed1996

Hydroxyurea and sickle cell anemia. Clinical utility of a myelosuppressive "switching" agent. The Multicenter Study of Hydroxyurea in Sickle Cell Anemia.

Painful crises in patients with sickle cell anemia are caused by vaso-occlusion and infarction. Occlusion of blood vessels depends on (at least) their diameter, the deformability of red cells, and the adhesion of blood cells to endothelium. Deoxygenated sickle cells are rigid because they contain linear polymers of hemoglobin S (Hb S); polymerization is highly concentration dependent, and dilution of Hb S by a nonsickling hemoglobin such as fetal hemoglobin (Hb F) would be expected to lead ultimately to a decrease in the frequency of painful crises. It might also be expected to decrease the severity of anemia, although the pathogenesis of anemia in sickle cell anemia (SS disease) is not clearly understood. Reversion to production of fetal rather than adult hemoglobin became practical with the discovery that HU was an orally effective and relatively safe "switching agent." Preliminary dose-ranging studies led to a double-blind randomized controlled clinical trial, the Multicenter Study of Hydroxyurea in Sickle Cell Anemia (MSH), designed to test whether patients treated with HU would have fewer crises than patients treated with placebo. The MSH was not designed to assess the mechanism(s) by which a beneficial effect might be achieved, but it was hoped that observations made during the study might illuminate that question. The 2 MSH treatment groups were similar to each other and were representative of African-American patients with relatively severe disease. The trial was closed earlier than expected, after demonstration that median crisis rate was reduced by almost 50% (2.5 versus 4.5 crises per year) in patients assigned to HU therapy. Hospitalizations, episodes of chest syndrome, and numbers of transfusions were also lower in patients treated with HU. Eight patients died during the trial, and treatment was stopped in 53. There were no instances of alarming toxicity. Patients varied widely in their maximum tolerated doses, but it was not clear that all were taking their prescribed treatments. When crisis frequency was compared with various clinical and laboratory measurements, pretreatment crisis rate and treatment with HU were clearly related to crisis rate during treatment. Pretreatment laboratory measurements were not associated with crisis rates during the study in either treatment group. It was not clear that clinical improvement was associated with an increase in Hb F. Crisis rates of the 2 treatment groups became different within 3 months. Mean corpuscular volumes (MCVs) and the proportion of Hb F containing red cells (F cells) rose, and neutrophil and reticulocyte counts fell, within 7 weeks. When patients were compared on the basis of 2-year crisis rates, those with lower crisis rates had higher F-cell counts and MCVs and lower neutrophil counts. Neutrophil, monocyte, reticulocyte, and platelet counts were directly associated, and F cells and MCV were inversely associated, with crisis rates in 3-month periods. In multivariable analyses, there was strong evidence of independent association of lower neutrophil counts with lower crisis rates. F-cell counts were associated with crisis rate only in the first 3 months of treatment; MCV showed an association over longer periods of time. Overall, the evidence that decreased neutrophil counts played a role in reducing crisis rates was strong. Increased F cells or MCV and evidence of cytoreduction by HU were also associated with decreased crisis rates, but no definitive statement can be made regarding the mechanism of action of HU because the study was not designed to address that question. Future studies should be designed to explore the mechanism of action of HU, to identify the optimal dosage regimen, and to study the effect of HU when combined with other antisickling agents.

Adolescent↗
PubMed1996

Cost-effectiveness of directly observed versus self-administered therapy for tuberculosis.

Decision analysis was used to compare three alternative strategies for a 6-mo course of treatment for tuberculosis: directly observed drug therapy (DOT), self-administered fixed-dose combination drug therapy, and self-administered conventional individual drug therapy. Estimates of effectiveness were obtained from the published literature. Estimates of costs were obtained from the literature and the Baltimore City Health Department. Both DOT and fixed-dose combination therapy were less costly and more effective than conventional therapy, although DOT was most cost-effective. In total, the average cost per patient treated was $13,925 for DOT, $13,959 for fixed-dose combination therapy, and $15,003 for conventional therapy. Per 1,000 patients treated, 31 relapses and three deaths could be expected for DOT, 96 relapses and eight deaths for fixed-dose combination therapy, and 133 relapses and 13 deaths for conventional therapy. The marginal cost-effectiveness of DOT relative to fixed-dose combination therapy was most sensitive to variability in the direct cost of DOT and less sensitive to relapse rates for DOT and fixed-dose combination therapy. The inferior cost-effectiveness of conventional therapy was not sensitive to plausible variability in cost or effectiveness. Both DOT and fixed-dose combination therapy were cost-effective relative to conventional therapy, although DOT is probably most cost-effective.

Antitubercular Agents↗
PubMed1995

Clostridium difficile colitis: an efficient clinical approach to diagnosis.

OBJECTIVE: To define clinical and laboratory variables that suggest the presence of Clostridium difficile colitis and to establish the number of stool specimens needed to reasonably exclude the diagnosis of C. difficile colitis. DESIGN: Prospective study of consecutive inpatients whose stool specimens were sent to be evaluated for the presence of C. difficile toxin. SETTING: University teaching hospital. PATIENTS: 268 hospital inpatients in medical, surgical, and gynecology units. MEASUREMENTS: Structured history and physical examination; detection of C. difficile toxin by cytotoxin tissue-culture assay with anti-C. difficile antiserum neutralization and by enzyme-linked immunoassay (EIA) for C. difficile toxins A and B; and detection of fecal leukocytes by microscopic examination and by latex agglutination lactoferrin assay. RESULTS: 43 of 268 consecutive inpatients were positive for C. difficile toxin by EIA or tissue-culture assay. Although toxin was detected by EIA alone in 39 of the 43 patients, it was detected in an additional 4 patients (10%) by tissue-culture assay alone. Univariate and multivariate logistic regression analysis showed that the following clinical and laboratory features were associated with C. difficile toxin positivity: the onset of diarrhea 6 or more days after the administration of antibiotics (odds ratio, 1.38 [95% CI, 1.10 to 3.79]); hospital stay longer than 15 days (odds ratio, 1.33 [CI, 1.09 to 3.95]); the presence of fecal leukocytes determined by microscopy (odds ratio, 2.39 [CI, 1.05 to 5.42]) or lactoferrin assay (odds ratio, 3.74 [CI, 1.80 to 7.76]); the presence of semiformed (as opposed to watery) stools (odds ratio, 2.33 [CI, 1.10 to 4.90]); and cephalosporin use (odds ratio, 2.36 [CI, 1.10 to 5.09]). Toxin-positive patients were no more likely than controls to have had fever, abdominal pain or cramps, leukocytosis, green-colored diarrhea, or blood in the stool or to have received clindamycin or penicillin derivatives. Of the 43 patients with C. difficile toxin, 34 (79%) had positive results for the toxin on the first stool specimen, 5 (cumulative, 91%) had positive results on the second specimen, and 4 had positive results on the third specimen. Overall, the negative predictive value of the first stool specimen was 97%. All patients who had two or more clinical or laboratory predictors were diagnosed with C. difficile disease when either the first or the second stool specimen was positive for toxin. CONCLUSIONS: Clinicians at the bedside can use readily available clinical and laboratory information to decide which patients are likely to have C. difficile disease and when it is appropriate and useful to order specific diagnostic tests for C. difficile toxin. Such data are also useful in determining the number of stool samples that reasonably excludes the diagnosis of C. difficile colitis.

Aged↗
PubMed1995

Neutropenia and bacterial infection in acquired immunodeficiency syndrome.

BACKGROUND: In human immunodeficiency virus (HIV) disease, neutropenia occurs most commonly in patients who are also severely immunosuppressed. It is not currently known whether neutropenia is an independent risk factor for the development of bacterial infection, which is a potentially serious complication of advanced HIV disease. METHODS: We compared the incidence of bacterial infection between 118 neutropenic patients (absolute neutrophil count [ANC], < 1 x 10(9)/L) and 118 nonneutropenic patients matched for CD4+ lymphocyte count, use of injecting drugs, and follow-up time from a demographically heterogeneous urban cohort of HIV-infected patients followed up longitudinally at the Johns Hopkins Hospital. The incidence of serious infection was analyzed separately for patients with an ANC of less than 1, less than 0.75, or less than 0.5 x 10(9)/L. RESULTS: There were no statistically significant associations found between neutropenia and several individual bacterial infections, including bacteremia, pneumonia, endocarditis, bacterial enterocolitis, and infection of normally sterile sites for any level of neutropenia. However, for all these infections combined, the adjusted relative risk for the occurrence of bacterial infection was 2.33 (95% confidence interval, 1.00 to 5.40; P = .05) for patients with an ANC of less than 1 x 10(9)/L and 7.92 (95% confidence interval, 1.18 to 53.2; P = .03) for those with an ANC of less than 0.5 x 10(9)/L. The incidence of serious bacterial infection ranged from two to three infections per 100 person-months of neutropenia for patients with an ANC of less than 1 x 10(9)/L and three to five infections per 100 person-months of neutropenia for patients with an ANC of less than 0.5 x 10(9)/L for all bacterial infections combined. CONCLUSIONS: Our matched cohort analysis indicates that neutropenia is an independent risk factor for bacterial infection in patients with advanced HIV disease. Given the incidence of infection, the cost-effectiveness of interventions to prevent neutropenia in advanced HIV disease should be assessed.

AIDS-Related Opportunistic Infections↗
PubMed1995

Race, sex, drug use, and progression of human immunodeficiency virus disease.

BACKGROUND: The rates of progression of human immunodeficiency virus (HIV) infection and survival have been reported to differ among sociodemographic groups. It is unclear whether these differences reflect biologic differences or differences in access to medical care. METHODS: We measured disease progression and survival in a cohort of 1372 patients seropositive for HIV who were treated at a single urban center (median follow-up, 1.6 years). We calculated the rates of survival for the entire cohort and the rates of progression to the acquired immunodeficiency syndrome (AIDS) or death among the 740 patients who presented without AIDS. We used Cox proportional-hazards analysis to examine factors associated with progression to AIDS and death. RESULTS: Progression to AIDS or death was associated with a CD4 cell count of 201 to 350 per cubic millimeter (relative risk, 2.0; P < 0.001), the presence of symptoms at base line (relative risk, 2.0; P < 0.001), prior antiretroviral therapy (relative risk, 1.7; P = 0.003), and older age (relative risk per year of age, 1.02; P = 0.03). However, there was no relation between disease progression and sex, race, injection-drug use, income, level of education, or insurance status. In the entire cohort, a lower CD4 cell count, a diagnosis of AIDS, older age, and the receipt of antiretroviral therapy before enrollment were associated with an increased risk of death, whereas the use of prophylaxis against pneumocystis pneumonia, zidovudine use after enrollment, and having a job at base line were associated with lower risks of death. There was no significant difference in survival between men and women, blacks and whites, injection-drug users and those who did not use drugs, or patients whose median annual incomes were $5,000 or less and those whose incomes were more than $5,000. CONCLUSIONS: Among patients with HIV infection who received medical care from a single urban center, there were no differences in disease progression or survival associated with sex, race, injection-drug use, or socioeconomic status. Differences found in other studies may reflect differences in the use of medical care.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Effect of hydroxyurea on the frequency of painful crises in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea in Sickle Cell Anemia.

BACKGROUND: In a previous open-label study of hydroxyurea therapy, the synthesis of fetal hemoglobin increased in most patients with sickle cell anemia, with only mild myelotoxicity. By inhibiting sickling, increased levels of fetal hemoglobin might decrease the frequency of painful crises. METHODS: In a double-blind, randomized clinical trial, we tested the efficacy of hydroxyurea in reducing the frequency of painful crises in adults with a history of three or more such crises per year. The trial was stopped after a mean follow-up of 21 months. RESULTS: Among 148 men and 151 women studied at 21 clinics, the 152 patients assigned to hydroxyurea treatment had lower annual rates of crises than the 147 patients given placebo (median, 2.5 vs. 4.5 crises per year, P < 0.001). The median times to the first crisis (3.0 vs. 1.5 months, P = 0.01) and the second crisis (8.8 vs. 4.6 months, P < 0.001) were longer with hydroxyurea treatment. Fewer patients assigned to hydroxyurea had chest syndrome (25 vs. 51, P < 0.001), and fewer underwent transfusions (48 vs. 73, P = 0.001). At the end of the study, the doses of hydroxyurea ranged from 0 to 35 mg per kilogram of body weight per day. Treatment with hydroxyurea did not cause any important adverse effects. CONCLUSIONS: Hydroxyurea therapy can ameliorate the clinical course of sickle cell anemia in some adults with three or more painful crises per year. Maximal tolerated doses of hydroxyurea may not be necessary to achieve a therapeutic effect. The beneficial effects of hydroxyurea do not become manifest for several months, and its use must be carefully monitored. The long-term safety of hydroxyurea in patients with sickle cell anemia is uncertain.

Adult↗
PubMed1995

Hospital admissions of HIV-infected patients from 1988 to 1992 in Maryland.

To determine how the patterns of inpatient hospital care for HIV-infected patients have evolved in recent years, we analyzed data obtained from a statewide hospital discharge database from Maryland for the years 1988, 1990, and 1992. For each of these years, we compared demography, diagnoses, lengths of stay, use of the intensive care unit, third-party payer, and hospital charges (inflation-adjusted to 1992 dollars). HIV-infected patients accounted for 0.42% of all Maryland's hospital admissions in 1988, 0.68% in 1990, and 1.1% in 1992, with progressively more women and African-Americans hospitalized. Average lengths of stay fell from 11.7 days (1988) to 10.7 days (1990) and 9.5 days (1992) (p < 0.0001). Average charges per admission fell from $11,634 (1988) to $9,938 (1990) and $8,618 (1992) (p < 0.0001). Medicare or Medicaid paid for 50.9% of hospital admissions in 1988, 56.8% in 1990, and 66.8% in 1992 (p < 0.001). In-hospital mortality rates (7.8% in 1988, 7.9% in 1990, and 7.7% in 1992; p = 0.783) were stable, as was severity of illness. P. carinii pneumonia (PCP) was the most common principal diagnosis, but it declined in prevalence from 13.6% in 1988 to 9.1% in 1992 (p < 0.0001). Principal diagnoses of other opportunistic infections remained stable (8.0% in 1988, 9.9% in 1990, 8.6% in 1992; p = 0.90), as did other nonopportunistic infections (32.8% in 1988, 27.2% in 1990, and 30.0% in 1992; p = 0.16). Non-PCP pneumonias increased from 7.6% (1988) to 10.2% (1992) (p < 0.0001). Substance abuse as a principal or secondary diagnosis increased from 30.9% (1988) to 34.3% (1992) (p < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗
PubMed1995

Studies on new acidic azoles as glucose-lowering agents in obese, diabetic db/db mice.

Bioisosteric substitution was used as a tool to generate several new structural alternatives to the thiazolidine-2,4-dione and tetrazole heterocycles as potential antidiabetic agents. Among the initial leads that emerged from this strategy, a family of acidic azoles, isoxazol-3- and -5-ones and a pyrazol-3-one, showed significant plasma glucose-lowering activity (17-42% reduction) in genetically obese, diabetic db/db mice at a dose of 100 mg/kg/day x4. Structure-activity relationship studies determined that 5-alkyl-4-(arylmethyl)pyrazol-3-ones, which exist in solution as aromatic enol/iminol tautomers, were the most promising new class of potential antidiabetic agent (32-45% reduction at 20 mg/kg/d x4). Included in this work are convenient syntheses for several types of acidic azoles that may find use as new acidic bioisosteres in medicinal chemistry such as the antidiabetic lead 5-(trifluoromethyl)pyrazol-3-one (hydroxy tautomer) and aza homologs of the pyrazolones, 1,2,3-triazol-5-ones (hydroxy tautomer) and 1,2,3,4-tetrazol-5-one heterocycles. log P and pKa data for 15 potential acidic bioisosteres, all appended to a 2-naphthalenylmethyl residue so as to maintain a similar distance between the acidic hydrogen and arene nucleus, are presented. This new data set allows comparison of a wide variety of potential acid mimetics (pKa 3.78-10.66; log P -0.21 to 2.76) for future drug design.

Animals↗
PubMed1995

An analysis of fetal hemoglobin variation in sickle cell disease: the relative contributions of the X-linked factor, beta-globin haplotypes, alpha-globin gene number, gender, and age.

Five factors have been shown to influence the 20-fold variation of fetal hemoglobin (Hb F) levels in sickle cell anemia (SS): age, sex, the alpha-globin gene number, beta-globin haplotypes, and an X-linked locus that regulates the production of Hb F-containing erythrocytes (F cells), ie, the F-cell production (FCP) locus. To determine the relative importance of these factors, we studied 257 Jamaican SS subjects from a Cohort group identified by newborn screening and from a Sib Pair study. Linear regression analyses showed that each variable, when analyzed alone, had a significant association with Hb F levels (P < .05). Multiple regression analysis, including all variables, showed that the FCP locus is the strongest predictor, accounting for 40% of Hb F variation. beta-Globin haplotypes, alpha-globin genes, and age accounted for less than 10% of the variation. The association between the beta-globin haplotypes and Hb F levels becomes apparent if the influence of the FCP locus is removed by analyzing only individuals with the same FCP phenotype. Thus, the FCP locus is the most important factor identified to date in determining Hb F levels. The variation within each FCP phenotype is modulated by factors associated with the three common beta-globin haplotypes and other as yet unidentified factor(s).

Adolescent↗
PubMed1995

Design of the multicenter study of hydroxyurea in sickle cell anemia. Investigators of the Multicenter Study of Hydroxyurea.

The Multicenter Study of Hydroxyurea in Sickle Cell Anemia is a randomized double-blind placebo-controlled trial to test whether hydroxyurea can reduce the rate of painful crises in adult patients who have at least three painful crises per year. The sample size of 299 patients yields at least 90% power to detect a 50% or greater reduction in crisis rate. Dosage starts at 15 mg/kg/day and is titrated to the patient's maximum tolerated dose up to 35 mg/kg/day. Placebo dosage is titrated in similar fashion to maintain blinding. Attempts are made to ascertain medical contacts for at least 2 years after study entry. The Core Laboratory, Treatment Distribution Center, and Data Coordinating Center collaborate to provide standardized monitoring for toxicity and dose adjustments. The Core Laboratory also reduces the possibility of inadvertent unmasking of treatment assignment during review of hematologic data in clinical centers. An independent Crisis Review Committee classifies clinical events to assure that outcome evaluations are standardized and unbiased by knowledge of treatment assignments. The Data and Safety Monitoring Board assures scientific integrity of the study, as well as the safety and ethical treatment of study patients. We expect the study to determine whether or not treatment with hydroxyurea can offer significant clinical benefit to patients with the most common hereditary disorder among African-Americans in the United States.

Adult↗
PubMed1995

Clinical spectrum of herpes zoster in adults infected with human immunodeficiency virus.

To determine the incidence and clinical manifestations of herpes zoster in a hospital-based clinic for adults infected with human immunodeficiency virus (HIV), we reviewed the records of all patients for whom zoster was diagnosed at or after their first clinic visit. Fifty-two episodes of zoster occurred in 45 patients during 1,614 person-years of follow-up (incidence, 3.2 episodes per 100 person-years). The following major complications of zoster occurred in 12 patients (27%): ocular complications (5), neurological complications (4), and chronic atypical skin lesions (5). Six patients each had postherpetic neuralgia and bacterial superinfection, which were the common minor complications of zoster. Multivariate analysis revealed that only a low CD4 cell count (< or = 200/mm3) was predictive of a major complication of zoster (OR, 13.2; 95% CI, 1.52-114; P = .019). Thus, complications of herpes zoster are common in patients with HIV infection, especially those with advanced immunosuppression.

Adult↗
PubMed1995

Lack of association between acyclovir use and survival in patients with advanced human immunodeficiency virus disease treated with zidovudine. Zidovudine Epidemiology Study Group.

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.

AIDS-Related Complex↗
PubMed1995

Survival analysis of two controlled trials of rifabutin prophylaxis against Mycobacterium avium complex in AIDS.

OBJECTIVES: Rifabutin prophylaxis has been shown to significantly decrease the incidence of Mycobacterium avium complex (MAC) bacteremia in two randomized controlled clinical trials, but a survival benefit has not been observed. An analysis of complete follow-up of these patients through August 1992 was performed to assess subsequent survival, because although follow-up in the previous trials was limited at the time of initial analysis, the analysis did suggest that a survival benefit might be emerging. METHODS: Data from 1146 AIDS patients with CD4+ counts < or = 200 x 10(6)/l enrolled at 73 US and Canadian sites in two clinical trials of MAC prophylaxis were analyzed using Cox proportional hazards analysis with rifabutin use modeled as a time-dependent covariate, taking into account the initial randomized double-blind phase of the trials and the subsequent open-label phase of follow-up of those patients. Survival from date of enrollment was analyzed. Other covariates adjusted for in the analysis were CD4+ lymphocytes count, Karnofsky performance score and hospitalization for opportunistic complications of AIDS. RESULTS: Patients who received open-label rifabutin may have had a better prognosis than those who did not, based on Karnofsky score and occurrence of opportunistic disease. Adjusting for these variables and for use of rifabutin as time-dependent covariates, the relative hazard (RH) of dying while receiving rifabutin prophylaxis was 0.74 for the entire cohort [95% confidence interval (CI), 0.60-0.91; P < 0.004]. For patients with an enrollment CD4+ count < or = 50 x 10(6)/l (n = 655), the RH was 0.75 (95% CI, 0.58-0.98), and for patients with an enrollment CD4+ count of > 50 x 10(6)/l (n = 491), the RH was 0.69 (95% CI, 0.49-0.99). CONCLUSIONS: An analysis of the combined double-blind and open-label follow-up of two clinical trials of rifabutin prophylaxis for MAC supports the suggestion of the double-blind study that rifabutin improves survival of AIDS patients.

AIDS-Related Opportunistic Infections↗
PubMed1995

Community-acquired pneumonia: impact of immune status.

This cross-sectional and prospective one year study evaluated adults admitted to an inner city hospital with community-acquired pneumonia. The study used extensive diagnostic methods to evaluate the etiologies of community-acquired pneumonia in hospitalized patients with differing immunologic status. Of 385 study patients, concurrent problems associated with immunosuppression were noted in 221 (57%) patients, 180 of whom were human immunodeficiency virus (HIV)-infected. The five most common causes of community-acquired pneumonia were: Streptococcus pneumoniae, Pneumocystis carinii, aspiration, Hemophilus influenzae, and gram-negative bacilli. Only 8.3% of patients had either Legionella, Chlamydia pneumoniae or Mycoplasma pneumoniae. Despite use of state-of-the-art diagnostic techniques, no diagnosis was made in 46 of 180 (25.6%) HIV-infected patients, 56 of 164 (34.1%) immunocompetent patients, and 20 of 41 (48.8%) non-HIV-infected immunosuppressed patients. The diagnostic yield of pre-antibiotic sputum culture for conventional bacteria was 99/155 (63.9%) compared to 52 of 169 patients (32.7%) with adequate post-antibiotic sputum culture (p < 0.0001). Although S. pneumonia continues to be the most commonly identified etiologic agent of community-acquired pneumonia, it is surpassed by P. carinii in the HIV-infected patient population. The apparent decline in the frequency of S. pneumoniae in our series presumably reflects administration of antibiotics prior to procurement of sputum culture. The paucity of atypical agents in this study support the current American Thoracic Society guidelines for selective use of macrolide therapy in immunocompetent adults hospitalized with community-acquired pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDS-Related Opportunistic Infections↗