Neonatal sepsis in rural India: timing, microbiology and antibiotic resistance in a population-based prospective study in the community setting.

OBJECTIVE: To examine the timing and microbiology of neonatal sepsis in a population-based surveillance in the Indian community setting. STUDY DESIGN: All live born infants in 223 villages of Odisha state were followed at home for 60 days. Suspect sepsis cases were referred to study hospitals for further evaluation including blood culture. RESULTS: Of 12 622 births, 842 were admitted with suspected sepsis of whom 95% were 4 to 60 days old. Culture-confirmed incidence of sepsis was 6.7/1000 births with 51% Gram negatives (Klebsiella predominating) and 26% Gram positives (mostly Staphylococcus aureus). A very high level of resistance to penicillin and ampicillin, moderate resistance to cephalosporins and extremely low resistance to Gentamicin and Amikacin was observed. CONCLUSION: The bacterial burden of sepsis in the Indian community is not high. Judicious choice of empiric antibiotics, antibiotic stewardship and alternate modalities should be considered for the management or prevention of neonatal sepsis in India.

Zidovudine and stavudine sequencing in HIV treatment planning: findings from the CHORUS HIV cohort.

BACKGROUND: Optimal sequencing of zidovudine and stavudine in antiretroviral therapy has not been elucidated. OBJECTIVE: To examine the impact of the sequence of therapeutic regimens containing zidovudine and stavudine on HIV-1 RNA and CD4 lymphocyte counts over 12 months. DESIGN: Observational, multicenter, longitudinal cohort study. SETTING: Four large outpatient, HIV practices participating in the community-based Collaborations in HIV Outcomes Research-U.S. (CHORUS) cohort study. PARTICIPANTS: 940 HIV-infected patients. METHODS: Comparison of HIV-1 RNA and CD4 lymphocyte responses in patients sequenced from zidovudine to stavudine or from stavudine to zidovudine using repeated measures regression models fit to outcomes by application of generalized estimating equation (GEE) methodology. RESULTS: Patients treated with zidovudine prior to stavudine (n = 834) achieved a greater mean drop from baseline HIV-1 RNA (p = .01) and higher proportion of undetectable HIV-1 RNA results (p = .05) over 12 months than those sequenced from stavudine to zidovudine (n = 106). CD4+ lymphocyte increases did not differ between the groups (p = .6). CONCLUSIONS: Prior zidovudine therapy was not associated with long-term attenuation of HIV-1 RNA or CD4 response to subsequent stavudine-containing regimens. Zidovudine before stavudine may have benefit in a strategic long-term therapeutic plan.

Respiratory disease trends in the Pulmonary Complications of HIV Infection Study cohort. Pulmonary Complications of HIV Infection Study Group.

We examined trends in the incidence of specific respiratory disorders in a multicenter cohort with progressive human immunodeficiency virus (HIV) disease during a 5-yr period. Individuals with a wide range of HIV disease severity belonging to three transmission categories were evaluated at regular intervals and for episodic respiratory symptoms using standard diagnostic algorithms. Yearly incidence rates of respiratory diagnoses were assessed in the cohort as a whole and according to CD4 count or HIV transmission category. The most frequent respiratory disorders were upper respiratory tract infections, but the incidence of lower respiratory tract infections increased as CD4 counts declined. Specific lower respiratory infections followed distinctive patterns according to study-entry CD4 count and transmission category. Acute bronchitis was the predominant lower respiratory infection of cohort members with entry CD4 counts > or = 200 cells/mm3. In cohort members with entry CD4 counts of 200 to 499 cells/mm3, the incidence of bacterial and Pneumocystis carinii pneumonia each increased an average of 40% per year. In members with entry CD4 counts < 200 cells/mm3, acute bronchitis, bacterial pneumonia, and P. carinii pneumonia occurred at high rates without discernible time trends, despite chemoprophylaxis in more than 80% after Year 1, and the rate of other pulmonary opportunistic infections increased over time. Each year, injecting drug users had a higher incidence of bacterial pneumonia than did homosexual men. The yearly rate of tuberculosis was < 3 episodes/100 person-yr in each entry CD4 and HIV-transmission group. We conclude that the time trends of HIV-associated respiratory disorders are determined by HIV disease stage and influenced by transmission category. Whereas acute bronchitis is prevalent during all stages of HIV infection, incidence rates of bacterial pneumonia and P. carinii pneumonia rise continuously during progression to advanced disease. In advanced disease, the incidence of acute bronchitis, bacterial pneumonia and P. carinii pneumonia is high despite widespread chemoprophylaxis.

Incidence of tuberculosis in the United States among HIV-infected persons. The Pulmonary Complications of HIV Infection Study Group.

BACKGROUND: The resurgence of tuberculosis in the United States is largely linked to the human immunodeficiency virus (HIV) epidemic. Despite this link, the epidemiology of tuberculosis and preventive strategies in patients infected with HIV are not completely understood. OBJECTIVES: To determine the incidence and predictors of tuberculosis in HIV-infected persons. DESIGN: Prospective, multicenter cohort study. SETTING: Community-based cohort of persons with and without HIV infection at centers in the eastern, midwestern, and western United States. PARTICIPANTS: 1130 HIV-seropositive patients without AIDS who were followed for a median of 53 months (814 homosexual men, 261 injection drug users, and 55 women who had acquired HIV through heterosexual contact). MEASUREMENTS: Delayed hypersensitivity response to purified protein derivative (PPD) tuberculin and mumps antigen, CD4 T-lymphocyte counts, and frequency of tuberculosis. RESULTS: 31 HIV-seropositive patients developed tuberculosis (0.7 cases per 100 person-years [95% CI, 0.5 to 1.0]). The most important demographic risk factor was location (adjusted risk ratio for eastern compared with midwestern and western United States, 4.1 [CI, 2.0 to 8.4]). Tuberculosis occurred more frequently in persons with CD4 counts of less than 200 cells/mm3 (1.2 cases per 100 person-years [CI, 0.7 to 1.9]) than in those with higher counts (0.5 cases per 100 person-years [CI, 0.3 to 0.8]). The rate of tuberculosis was highest among tuberculin converters (5.4 cases per 100 person-years [CI, 1.1 to 15.7]), lower among patients who were PPD positive at first testing (4.5 cases per 100 person-years [CI, 1.6 to 9.7]), and lowest among patients who remained PPD negative (0.4 cases per 100 person-years [CI, 0.2 to 0.7]). Tuberculosis was not reported among persons who had PPD reactions of 1 to 4 mm. Compared with that of patients who tested positive for mumps, the risk for tuberculosis of those who tested negative was increased about sevenfold if they were PPD positive (P < 0.03) and fourfold if they were PPD negative (P < 0.02). CONCLUSIONS: Incidence of tuberculosis was higher in the eastern United States, in patients with CD4 counts of less than 200 cells/mm3, and in PPD-positive patients. Analysis of tuberculin reaction size supports the current interpretive criteria of the Centers for Disease Control and Prevention. Nonreactivity to mumps antigen indicated increased risk for tuberculosis independent of PPD response.

Lack of usefulness of radiographic screening for pulmonary disease in asymptomatic HIV-infected adults. Pulmonary Complications of HIV Infection Study Group.

OBJECTIVE: To determine the use of chest radiographs in the screening of asymptomatic adults infected with the human immunodeficiency virus (HIV). METHODS: A prospective, multicenter study of the pulmonary complications of HIV infection in a community-based cohort of persons with and without HIV infection. The subjects included 1065 HIV-seropositive subjects without the acquired immunodeficiency syndrome at the time of enrollment: 790 homosexual men, 226 injection drug users, and 49 women with heterosexually acquired infection. Frontal and lateral chest radiographs were performed at 3-, 6-, and 12-month intervals, CD4 lymphocyte measurements at 3- and 6-month intervals, tuberculin and mumps skin tests at 12-month intervals, and medical histories and physical examinations at 3- and 6-month intervals. Pulmonary diagnoses that occurred within 2 months following each radiograph were analyzed and correlated with the radiographic results. RESULTS: Evaluable screening chest radiographs (5263) were performed in HIV-seropositive subjects while they were asymptomatic; of these, 5140 (98%) were classified as normal and 123 (2%) as abnormal. A new pulmonary diagnosis was identified within 2 months following a screening radiograph in 55 subjects. Only 11 of these subjects had abnormal radiographs; the sensitivity of the radiograph was 20%. The sensitivity was similarly low at baseline, within each transmission category, and in subjects whose CD4 lymphocyte counts were less than 0.2 x 10(9)/L (200/microL). The types of pulmonary diseases that occurred were similar in the subjects with normal and abnormal screening radiographs. CONCLUSION: Screening chest radiography in asymptomatic HIV-infected adults is unwarranted because the diagnostic yield is low.

Routine analysis of induced sputum is not an effective strategy for screening persons infected with human immunodeficiency virus for Mycobacterium tuberculosis or Pneumocystis carinii. Pulmonary Complications of HIV Infection Study Group.

A prospective multicenter cohort study comprising 1,171 individuals who were seropositive for human immunodeficiency virus (HIV) but did not have AIDS at the time of enrollment and 182 HIV-seronegative controls, was studied by means of routine induced-sputum analysis in an attempt to detect occult tuberculosis or Pneumocystis carinii pneumonia. One occult case of tuberculosis was discovered upon the patient's enrollment (at baseline); none were discovered during follow-up. Two additional Mycobacterium tuberculosis isolates were recovered (one at baseline, one during follow-up) from subjects with symptoms or abnormalities evident on chest roentgenograms. Three specimens were false-positive (one for M. tuberculosis, two for P. carinii). Five pathogenic nontuberculous mycobacteria isolates were recovered during follow-up. Nonpathogenic, nontuberculous mycobacteria were recovered from 51 (4.6%) of 1,113 baseline specimens and 56 (3.7%) of 1,518 follow-up specimens, primarily at a center where the water supply was contaminated. We conclude that routine induced-sputum analysis is not an effective strategy for screening HIV-infected asymptomatic subjects for tuberculosis or P. carinii pneumonia before the onset of clinically recognizable disease activity.

Respiratory illness in persons with human immunodeficiency virus infection. The Pulmonary Complications of HIV Infection Study Group.

Although the pulmonary complications of advanced human immunodeficiency virus (HIV) infection have been well described, there is little information on respiratory manifestations of earlier disease. This report describes the respiratory disorders diagnosed over an 18-month period in a cohort of persons with or at risk for HIV infection with variable immunologic status. Cohort members were followed routinely and evaluated for respiratory disease by standard diagnostic algorithms. The 18-month incidence of each respiratory diagnosis was determined, and for frequent diagnoses, incidence by transmission category, location of residence, smoking status, CD4 count, and performance score at entry were compared. The most frequent respiratory diagnoses in HIV-seropositive cohort members were common to the general population: upper respiratory infection (33.4%), acute bronchitis (16.0%), acute sinusitis (5.3%), and bacterial pneumonia (4.8%). Pneumocystis carinii pneumonia occurred in 3.9%. Ambulatory respiratory illnesses were reported frequently regardless of immunologic status. The rates of P. carinii pneumonia and bacterial pneumonia were significantly greater in cohort members with entry CD4 counts < 250. Bacterial pneumonia occurred more frequently in injecting drug users and in cohort members with entry Karnofsky scores < 90. Disease stage and demographic and exposure factors are important variables affecting the respiratory manifestations of HIV infection.

Tuberculin and anergy testing in HIV-seropositive and HIV-seronegative persons. Pulmonary Complications of HIV Infection Study Group.

OBJECTIVE: To determine the prevalence and predictors of reactivity to tuberculin purified protein derivative (PPD) and skin test anergy in patients with human immunodeficiency virus (HIV) infection and in HIV-seronegative controls. DESIGN: Cross-sectional analysis of baseline data from a prospective, multicenter study of pulmonary complications of HIV infection. SETTING: Community-based cohort of persons with and without HIV infection. PATIENTS: A total of 1171 HIV-seropositive patients without AIDS (841 homosexual men, 274 intravenous drug users, and 56 women with heterosexually acquired infection); 182 HIV-seronegative persons (125 homosexual men and 57 intravenous drug users). MEASUREMENTS: Delayed-type hypersensitivity response to tuberculin PPD, trichophytin, mumps, and Candida antigens; T-lymphocyte subsets. RESULTS: The prevalence of tuberculin PPD reactivity was higher among intravenous drug users than among homosexual men, in both HIV-seronegative (19.1% compared with 6.8%, P = 0.03) and HIV-seropositive persons (15.1% compared with 2.5%, P < 0.001). Among HIV-infected patients, the prevalence of tuberculin reactivity varied directly and that of anergy inversely with the absolute CD4 lymphocyte count. Prevalences were 1% and 72%, respectively, in patients with fewer than 200 CD4 cells/mm3, and 8.4% and 25.5%, respectively, in those with 600 CD4 cells/mm3 (P < 0.001 for both comparisons). Patients with HIV infection and fewer than 400 CD4 lymphocytes/mm3 had a lower prevalence of PPD reactivity than HIV-seronegative controls (2.7% compared with 10.0%, P < 0.001). The strongest predictors of tuberculin reactivity were intravenous drug use, black race, a previous positive PPD test result, and a history of Calmette-Guérin bacillus vaccination. The strongest predictor of anergy was HIV seropositivity. CONCLUSIONS: The response to delayed-type hypersensitivity antigens depends on immune status. The value of PPD and anergy testing in HIV-seropositive patients depends on the ability of such testing to predict subsequent tuberculosis, which is imprecisely known. Until more data or better methods are available, these tests should be done as early as possible in the course of HIV infection.