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Biomedical subjects

N Salomon

Publications and source records attributed to N Salomon.

At least 19 recordsLinked to original sources

Evaluation of an intensive intermittent-induction regimen and duration of short-course treatment for human immunodeficiency virus-related pulmonary tuberculosis. Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA) and the AIDS Clinical Trials Group (ACTG).

This study examined whether adding levofloxacin to a standard four-drug regimen improved the 8-week culture response and compared effectiveness of 9 versus 6 months of intermittent therapy for human immunodeficiency virus-related pansusceptible pulmonary tuberculosis. Patients were randomized to receive either four or five drugs, the fifth being levofloxacin. Patients who completed induction therapy were randomized to complete 9 versus 6 months of intermittent therapy with isoniazid and rifampin. In the randomized induction phase, 97.3% of patients in the four-drug group and 95.8% in the five-drug group had sputum culture conversion at 8 weeks (P = 1.00). In the continuation phase, one patient (2%) assigned to 9 months and two patients (3.9%) assigned to 6 months of therapy had treatment failure/relapse (P = 1.00). In conclusion, this study showed that levofloxacin added no benefit to a highly effective, largely intermittent, four-drug induction regimen. Both 9 and 6 months of intermittent therapy were associated with low treatment failure/relapse rates.

AIDS-Related Opportunistic Infections

Widespread dissemination of a drug-susceptible strain of Mycobacterium tuberculosis.

In New York City, a large proportion of new tuberculosis cases has been caused by 1 drug-susceptible strain (called C strain) of Mycobacterium tuberculosis. Between 1991 and 1994, among >600 tuberculosis patients consecutively identified in four large hospitals in the city, 54 with C strain, 69 with non-C cluster pattern strains, and 42 with noncluster pattern strains were studied. Susceptibility to reactive nitrogen intermediates (RNI) of selected isolates was compared. In a case-control analysis, 51% of patients with C strain, 28% with non-C cluster strains (P < .05), and 14% with noncluster strains (P < .01) were found to be injection drug users. C strain but not 13 other unrelated isolates were resistant to RNI. Injection drug use may provide a selective pressure for an RNI-resistant tubercle bacillus to emerge, which may give the organism a biologic advantage and explain the widespread dissemination of C strain M. tuberculosis within the city.

Adolescent

Variation of chest radiographic patterns in pulmonary tuberculosis by degree of human immunodeficiency virus-related immunosuppression. The Terry Beirn Community Programs for Clinical Research on AIDS (CPCRA). The AIDS Clinical Trials Group (ACTG).

Our aim was to evaluate the effect of human immunodeficiency virus (HIV) disease stage on chest radiographic (CXR) findings among patients with HIV-related pulmonary tuberculosis (TB). Data are from a prospective multicenter treatment trial for HIV-related TB. Baseline CXR findings and CD4+ lymphocyte counts were compared among patients with HIV-related TB. Data from published studies describing CXR findings in HIV-infected patients were reviewed and a pooled-data analysis was conducted. Of 135 patients with culture-confirmed HIV-related TB, 128 had both CXR and CD4+ lymphocyte data. CD4+ lymphocyte counts of < 200/mm3 (n = 98) were significantly associated with hilar/mediastinal adenopathy on CXR (30%, vs. 7% with counts > or = 200/mm3; P = .01); counts of > or = 200/mm3 (n = 30) more frequently were associated with cavitation (20% vs. 7%; P = .08). Analyses of these results, pooled with other published data, confirmed these findings. This study demonstrates associations of certain CXR findings with HIV disease stage. Knowledge of the degree of immunosuppression is important when evaluating CXR findings in HIV-infected patients.

AIDS-Related Opportunistic Infections

Clinical features and outcomes of HIV-related cytomegalovirus pneumonia.

OBJECTIVE: To describe the characteristics and outcomes of HIV-infected patients with biopsy-proven cytomegalovirus (CMV) pneumonia. DESIGN: Retrospective study. SETTING: A 900-bed acute facility in New York City. PATIENTS: Eighteen HIV-infected patients with pathologically confirmed CMV inclusions in lung tissue without other pathogens and 36 control patients with biopsy-proven Pneumocystis carinii pneumonia (PCP) selected for comparisons by computer-generated random sequential numbers. MAIN OUTCOME MEASURES: Demographic, clinical, laboratory, radiological findings, and in-hospital mortality. RESULTS: Eighteen HIV-infected patients were found to have CMV lung infection alone. Pathologic findings were pneumonitis (n = 11); pneumonitis and pulmonary vasculitis (n = 1); and CMV inclusions alone (n = 6). All presented with respiratory symptoms (cough or dyspnea), 89% had fever, 83% had radiological abnormalities, and 56% had severe hypoxemia. The pulmonary presentation was similar except for higher lactate dehydrogenase (median, 449 versus 329 IU/l; P = 0.03) and presence of pleural effusions (33 versus 0%; P = 0.001) in CMV patients. Multivariate analysis showed that CD4 counts < or = 12 x 10(6)/l (odds ratio; 9.2; P = 0.029) and extrapulmonary CMV (odds ratio, 20.4; P = 0.039) were independently associated with CMV pneumonia. Seventeen patients received specific anti-CMV therapy for a mean of 22 +/- 13 days. In-hospital mortality was higher in patients with CMV pneumonia (odds ratio, 11.9; P = 0.002). The median time from admission to death was 31 days. CONCLUSIONS: CMV lung infection was seen in severely immunosuppressed HIV-positive patients and associated with clinical pneumonitis with high early mortality. Although the clinical features resemble PCP, the presence of extrapulmonary CMV disease should suggest the diagnosis of CMV pneumonia.

AIDS-Related Opportunistic Infections

Susceptibility to levofloxacin of Myocobacterium tuberculosis isolates from patients with HIV-related tuberculosis and characterization of a strain with levofloxacin monoresistance. Community Programs for Clinical Research on AIDS 019 and the AIDS Clinical Trials Group 222 Protocol Team.

OBJECTIVE: To characterize the susceptibility to levofloxacin of clinical isolates of Mycobacterium tuberculosis (MTB) obtained from patients with HIV-related tuberculosis and to characterize the molecular genetics of levofloxacin resistance. DESIGN AND METHODS: Isolates from culture-positive patients in a United States multicenter trial of HIV-related TB were tested for susceptibility to levofloxacin by minimum inhibitory concentration (MIC) determinations in Bactec 7H12 broth. Automated sequencing of the resistance determining region of gyrA was performed. RESULTS: Of the 135 baseline MTB isolates tested, 134 (99%; 95% exact binomial confidence interval, 95.9-99.9%) were susceptible to levofloxacin with an MIC < or = 1.0 microg/ml. We identified a previously unrecognized mis-sense mutation occurring at codon 88 of gyrA in a levofloxacin mono-resistant MTB isolate obtained from a patient with AIDS who had received ofloxacin for 8 months prior to the diagnosis of tuberculosis. CONCLUSIONS: Clinical MTB isolates from HIV-infected patients were generally susceptible to levofloxacin. However, the identification of a clinical isolate with mono-resistance to levofloxacin highlights the need for circumspection in the use of fluoroquinolones in the setting of potential HIV-related tuberculosis and for monitoring of rates of resistance of MTB isolates to fluoroquinolones.

AIDS-Related Opportunistic Infections

Implementation of universal directly observed therapy at a New York City hospital and evaluation of an out-patient directly observed therapy program.

SETTING: Directly observed therapy (DOT) program for tuberculosis (TB) at a New York City hospital. OBJECTIVE: To describe a specific TB DOT program model utilizing active prospective identification of inpatients, and identify factors associated with patient acceptance of voluntary DOT and with their retention in therapy. METHODS: Recruitment for DOT by daily surveillance of in-patients. DOT was offered as the patient's choice together with concrete services and incentives. On-site DOT was offered in an out-patient clinic. Outreach efforts were initiated when a patient missed one or more DOT visit. RESULTS: During the study period, 95% of 176 in-patients with TB were evaluated for DOT. Of the 137 who were eligible for DOT, 85% (95% confidence interval [CI], 77.5% to 90%) elected to receive DOT. Illicit drug use was independently associated with a higher likelihood of acceptance of DOT (odds ratio[OR], 4.88; 95% CI, 1.5-15.7). Among the 101 patients who received onsite DOT, illicit drug use (OR, 0.21; 95% CI, 0.08-0.6) and previous TB therapy (OR, 0.27; 95% CI, 0.27-0.7) were both independently associated with lower retention in therapy. However, with intensive case management, only 1% of this cohort was lost to follow-up and the overall treatment completion index was 98%. CONCLUSION: In-patient surveillance is a highly effective DOT recruitment strategy. A DOT model which elicits patient participation in discharge plans and offers incentives can yield a high rate of voluntary acceptance. Outpatient case management is a highly effective means of ensuring treatment completion, especially in those at risk for poor retention.

Adult

Multidrug-resistant tuberculosis in patients without HIV infection.

BACKGROUND: Investigations of outbreaks of multidrug-resistant tuberculosis have found low rates of treatment response and very high mortality, and they have mainly involved patients with advanced human immunodeficiency virus (HIV) infection. For patients without HIV infection, one study reported an overall rate of response to treatment of 56 percent, and the mortality from tuberculosis was 22 percent. We investigated treatment response and mortality rates in 26 HIV-negative patients in New York with multidrug-resistant tuberculosis. METHODS: We obtained detailed data from seven teaching hospitals in New York City on patients with multidrug-resistant tuberculosis--defined as tuberculosis resistant at least to isoniazid and rifampin--who were HIV-negative on serologic testing. Lengths of times from diagnosis to the initiation of appropriate therapy and from the initiation of appropriate therapy to conversion to negative cultures were assessed. Therapeutic responses were evaluated by both microbiologic and clinical criteria. RESULTS: Between March 1991 and September 1994, 26 HIV-negative patients were identified and treated. Of the 25 patients for whom adequate data were available for analysis, 24 (96 percent) had clinical responses; all 17 patients for whom data on microbiologic response were available had such a response. The median times from diagnosis to the initiation of appropriate therapy and from the initiation of therapy to culture conversion were 44 days (range, 0 to 181) and 69 days (range, 2 to 705), respectively. Side effects requiring the discontinuation of medication occurred in 4 of 23 patients (17 percent) who were treated with second-line antituberculosis medications. The median follow-up for the 23 patients who responded and who received appropriate therapy was 91 weeks (range, 41 to 225). CONCLUSIONS: In this report from New York City, HIV-negative patients with multidrug-resistant tuberculosis, contrary to previous reports, responded well to appropriate chemotherapy, both clinically and microbiologically.

Adult

Predictors and outcome of multidrug-resistant tuberculosis.

We identify early predictors of multidrug-resistant tuberculosis and describe improved clinical outcomes, including survival, for patients with human immunodeficiency virus (HIV)-related multidrug-resistant tuberculosis (MDR-TB) when they are prospectively identified and receive treatment under direct observation. Analysis by means of a Cox proportional hazards model revealed that failure to defervesce while receiving a standard four-drug antituberculous regimen was independently associated with multidrug resistance (P = .004). When patients with HIV-related MDR-TB were prospectively identified and treated with at least two agents that were active in vitro, 100% bacteriologic conversion and improved survival (> or = 4 months for 88% of patients and > or = 1 year for 59% of patients) were observed. For patients with HIV-related tuberculosis, poorer survival was associated with a CD4+ lymphocyte count of < 25 mm3 (P = .03); multidrug resistance was not a predictor of poor outcome (P = .82). These data suggest that patients with prolonged fever who are receiving antituberculous therapy may be an appropriate subgroup to target for broader empirical therapy. The findings also demonstrate that improved outcomes can be achieved with HIV-related MDR-TB when patients are prospectively identified and treated with agents that are active in vitro.

AIDS-Related Opportunistic Infections

Tuberculosis in drug users.

The rise in tuberculosis (TB) has disproportionately affected specific populations. Historically, many patients with TB became iatrogenic opiate addicts through therapeutic use of these drugs for symptom control. Demographic trends reshaped the relationship between drug use and TB into one in which drug use became a risk factor for tuberculosis as a result of the overlap of epidemiological and social factors associated with both drug use and TB. The spread of human immunodeficiency virus infection has amplified the spread of TB among drug users. We review the epidemiology of TB in drug users as well as the factors relevant to screening and compliance in drug-using populations. Drug users constitute a high-risk group for whom screening, prevention of infection, diagnosis, and treatment pose particular challenges. The development of TB services capable of engaging drug users (those both in and out of drug treatment programs) has potential for disrupting a significant chain of rapid TB transmission.

AIDS-Related Opportunistic Infections

Two-stage tuberculin skin testing in an HIV-infected population: a preliminary report.

To identify differences in purified protein derivative (PPD) tuberculin positivity rates and to assess the utility of sequential PPD testing among persons with HIV infection, we performed two sequential administrations of 5 tuberculin units of PPD in a group of persons with HIV infection. Eligible patients were skin-tested with the tuberculin using the Mantoux method. Patients who tested < 5 mm of induration were skin-tested seven days later along with Candida and mumps antigens. Of 37 tested patients, only 18 (49%) returned to have the first test read. Using a > or = 5 mm cutoff, 5 (28%) tested positive. Positivity varied markedly between patients with CD4+ cell counts under and at or over 400 cells/mm3 (0% vs. 56%). Among patients who had a reaction to the first test, the reaction was smaller in patients with CD4+ cell counts under 400 than in those with counts at or over 400 cells/mm3 (mean induration: 2.8 vs. 30.4 mm). Positivity was also less frequent in intravenous drug users than in nonusers (9% vs. 57%); these two groups did not differ with respect to CD4+ cell counts. Of the 13 patients who tested < 5 mm, only 8 (62%) kept their appointments to have the second test placed and read. Only 1 of these, a drug user with a CD4+ count of 6 cells/mm3, had a positive reaction with boosting from 4 mm on the first test to 10 mm on the second. These data indicate that PPD testing may be unreliable in screening for tuberculosis infection in persons with CD4+ counts < 400 cell/mm3.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Drug-resistant tuberculosis: factors associated with rise in resistance in an HIV-infected urban population.

Our objective was to characterize the population with tuberculosis (TB) and to identify factors predictive of resistance to anti-TB agents in an area of high prevalence of human immunodeficiency virus infection. We reviewed microbiology and clinical records from 1988 to 1991 at Beth Israel Medical Center, New York City, for patients with culture-proved TB and analyzed the frequency of resistance to anti-TB agents with respect to demographic and clinical variables. Of 360 patients with TB, 17.5% had drug-resistant isolates. Of the 333 patients on whom the information was available, 72% reported HIV risk factors, 54% injectable drug use, and nearly one-third homelessness. The majority (56%) had documented HIV infection. Between 1988 and 1991, acquired resistance to isoniazid (INH) alone rose from 5% to 21% and initial resistance to INH alone rose from 0% to 19%. Drug resistance was more likely in previously treated patients; 61% of the previously treated patients admitted noncompliance with therapy. Cavitary lung disease was the strongest predictor of acquired drug resistance. Initial drug resistance was more likely in patients with HIV infection. Among persons with HIV infection, none of the analyzed factors was found to be predictive of drug resistance. Noncompliance with therapy and the HIV epidemic played a major role in the rise of drug resistance in our population. HIV infection confounds the epidemiologic factors that might otherwise allow clinical prediction of resistance.

Adult

Aspergillosis in the acquired immunodeficiency syndrome.

The role of Aspergillus species as a pathogen in acquired immunodeficiency syndrome (AIDS) has not been clearly defined. From 1984 to 1989, more than 2,000 AIDS patients were seen at Beth Israel Medical Center, New York. Aspergillus was isolated in ten patients; seven had invasive disease and three had noninvasive disease. Invasive pulmonary aspergillosis (IPA) was diagnosed in six patients and invasive renal aspergillosis was found in one patient. Five were homosexual men and two were intravenous drug users. At presentation, all ten had fever, seven had cough, eight had dyspnea, and five had pleuritic chest pain. Chest roentgenograms revealed focal infiltrates in six patients, bilateral interstitial infiltrates in two patients, and bilateral pneumothoraces in one patient. Predisposing conditions included corticosteroid therapy in four, granulocytopenia (less than 1,000/cu m) in two, and broad-spectrum antibiotic therapy in five. Three of the four patients receiving corticosteroids received them as adjuvant therapy for Pneumocystis carinii pneumonia (PCP). Aspergillus was identified antemortem in eight patients, in bronchoalveolar lavage (BAL) fluid in six, in transbronchial biopsy specimen in three, in open lung biopsy specimen in one, and postmortem in one patient. Six of seven patients had at least one concomitant pulmonary process. Six underwent necropsy and findings showed IPA in three, disseminated aspergillosis in two, and PCP in one. Invasive aspergillosis, although significant, is uncommon in AIDS. When Aspergillus is isolated in the setting of corticosteroid therapy, antibiotics, or granulocytopenia, one must suspect invasive disease.

Acquired Immunodeficiency Syndrome

Evidence for an HIV-related nephropathy: a clinico-pathological study.

The existence of an HIV-related nephropathy as a distinct disease entity is controversial. We observed a high incidence of renal disease in our AIDS patients. Of 182 patients, 59 patients (32.4%) were found to have heavy proteinuria (greater than 2 g/24 h). Of these, 24 patients had slow progression of renal insufficiency and 2 patients had rapid deterioration to end stage renal disease. There was a notable absence of hypertension in these cases. The incidence of proteinuria was similar in blacks and hispanics; however 22.8% of blacks had renal insufficiency as compared to 6.9% of hispanics. There was no difference in the incidence of heavy proteinuria between intravenous drug abusers (32.3%) and nonabusers (33.3%). Renal morphology when examined showed characteristic changes, including cytomembranous structures and virus-like particles. These changes were similar in patients with heavy or light proteinuria, though they were less severe in the latter. We conclude that a HIV-related nephropathy exist and the presence of cytomembranous structures and virus-like particles in the renal tissue raises the possibility of a viral etiology for this disorder.

Acquired Immunodeficiency Syndrome