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Cross-resistance in rifamycins has been observed in rifampin (RIF)-resistant Mycobacterium tuberculosis complex isolates; some rpoB mutations do not confer broad in vitro rifamycin resistance. We examined 164 isolates, of which 102 were RIF-resistant, for differential resistance between RIF and rifabutin (RFB). A total of 42 unique single mutations or combinations of mutations were detected. The number of unique mutations identified exceeded that reported in any previous study. RFB and RIF MICs up to 8 μg/mL by MGIT 960 were studied; the cut-off values for susceptibility to RIF and RFB were 1 μg/mL and 0.5 μg/mL, respectively. We identified 31 isolates resistant to RIF but susceptible to RFB with the mutations D516V, D516F, 518 deletion, S522L, H526A, H526C, H526G, H526L, and two dual mutations (S522L + K527R and H526S + K527R). Clinical investigations using RFB to treat multidrug-resistant tuberculosis cases harboring those mutations are recommended., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Tuberculosis (TB) remains an important cause of hospitalization and mortality in the United States. Prevention of TB transmission in acute care facilities relies on prompt identification and implementation of airborne isolation, rapid diagnosis, and treatment of presumptive pulmonary TB patients. In areas with low TB burden, this strategy may result in inefficient utilization of airborne infection isolation rooms (AIIRs). We reviewed TB epidemiology and diagnostic approaches to inform optimal TB detection in low-burden settings. Published clinical prediction rules for individual studies have a sensitivity ranging from 81% to 100% and specificity ranging from 14% to 63% for detection of culture-positive pulmonary TB patients admitted to acute care facilities. Nucleic acid amplification tests (NAATs) have a specificity of >98%, and the sensitivity of NAATs varies by acid-fast bacilli sputum smear status (positive smear, ≥95%; negative smear, 50%-70%). We propose an infection prevention strategy using a clinical prediction rule to identify patients who warrant diagnostic evaluation for TB in an AIIR with an NAAT. Future studies are needed to evaluate whether use of clinical prediction rules and NAATs results in optimized utilization of AIIRs and improved detection and treatment of presumptive pulmonary TB patients.

Objectives: To examine trends in tuberculosis (TB) incidence and to compare demographic and clinical characteristics of nursing home (NH) residents and community-dwelling older adults., Design: Prospective TB surveillance., Setting: TB cases reported in California from 2000 to 2009., Participants: TB patients aged 65 and older., Measurements: Trends in TB incidence per 100,000 population were assessed using Poisson regression. Demographic and clinical characteristics were compared using the chi-square or Wilcoxon rank-sum test. Among NH residents, risk factors for death during TB treatment were identified using logistic regression., Results: From 2000 to 2009, TB incidence rates decreased significantly, from 15.9/100,000 to 8.4/100,000 (-44%, 95% confidence interval (CI) = -66% to -7%) for NH residents and from 21.2/100,000 to 15.0/100,000 (-27%, 95% CI = -29% to -24%) for community-dwelling older adults. Overall, 211 TB cases among NH residents and 6,518 cases among community-dwelling older adults were reported. NH residents were more likely than community-dwelling older adults to be older (median age 81 vs 75, P < .001), have a negative acid-fast bacilli sputum smear and positive culture (37% vs 28%, P < .001), and die while undergoing TB treatment (44% vs 14%, P < .001), and were less likely to have a positive tuberculin skin test (TST) (28% vs 44%, P < .001) and have TB care provided by a health department (20% vs 59%, P < .001). In multivariable analysis, NH residents who had a positive TST were less likely to die while undergoing TB treatment (odds ratio = 0.39, 95% CI = 0.16-0.96)., Conclusion: TB incidence rates were lower, and reductions in incidence were greater among NH residents; community-dwelling older adults had higher TB rates and smaller reductions in incidence. Interventions that promote timely detection and treatment of TB infection and disease may be needed to reduce morbidity and mortality among NH residents., (© 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.)

Background/aims: Few studies have compared population-based tuberculosis (TB) incidence rates by end-stage renal disease (ESRD) status. No studies have compared TB genotypes by ESRD status to determine whether TB disease resulted from recent transmission or reactivation of latent TB infection (LTBI). We calculated TB incidence rates and compared demographic and clinical characteristics and genotypes among TB cases by ESRD status., Methods: This analysis was based on prospective surveillance for TB cases during 2010 in California. Clustered genotype was defined as ≥2 culture-positive TB cases with matching genotypes in the same county. The χ(2) or Wilcoxon rank-sum test was used to compare variables., Results: During 2010, 83 TB cases with ESRD and 2,244 cases without ESRD were reported in California; TB incidence rates were 110.3/100,000 and 6.0/100,000, respectively. ESRD case patients versus patients without ESRD were more likely to be older (median age 66 vs. 49 years; p < 0.001), foreign-born persons who had arrived in the USA >5 years before TB diagnosis (97 vs. 75%; p < 0.001) and dead at TB diagnosis (7 vs. 2%; p = 0.01). ESRD patients were less likely to have a positive tuberculin skin test (50 vs. 80%; p < 0.001), positive acid-fast bacilli sputum smears (33 vs. 53%; p = 0.01) and cavities on chest radiography (6 vs. 21%; p = 0.01). No differences in proportions of clustered TB genotypes were detected (20 vs. 23%; p = 0.54)., Conclusions: Rates of TB are 18 times higher in California's ESRD population, and TB disease likely occurred due to LTBI reactivation because few patients had clustered genotypes. Efforts to prevent TB among ESRD patients may require the use of newer diagnostic tests and promotion of LTBI treatment.

Linezolid is used off-label to treat multidrug-resistant tuberculosis (MDR-TB) in absence of systematic evidence. We performed a systematic review and meta-analysis on efficacy, safety and tolerability of linezolid-containing regimes based on individual data analysis. 12 studies (11 countries from three continents) reporting complete information on safety, tolerability, efficacy of linezolid-containing regimes in treating MDR-TB cases were identified based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Meta-analysis was performed using the individual data of 121 patients with a definite treatment outcome (cure, completion, death or failure). Most MDR-TB cases achieved sputum smear (86 (92.5%) out of 93) and culture (100 (93.5%) out of 107) conversion after treatment with individualised regimens containing linezolid (median (inter-quartile range) times for smear and culture conversions were 43.5 (21-90) and 61 (29-119) days, respectively) and 99 (81.8%) out of 121 patients were successfully treated. No significant differences were detected in the subgroup efficacy analysis (daily linezolid dosage ≤ 600 mg versus >600 mg). Adverse events were observed in 63 (58.9%) out of 107 patients, of which 54 (68.4%) out of 79 were major adverse events that included anaemia (38.1%), peripheral neuropathy (47.1%), gastro-intestinal disorders (16.7%), optic neuritis (13.2%) and thrombocytopenia (11.8%). The proportion of adverse events was significantly higher when the linezolid daily dosage exceeded 600 mg. The study results suggest an excellent efficacy but also the necessity of caution in the prescription of linezolid.

To assess the clinical impact of a molecular beacon (MB) assay that detects multidrug-resistant tuberculosis (MDR TB), we retrospectively reviewed records of 127 MDR TB patients with and without MB testing between 2004 and 2007. Use of the MB assay reduced the time to detection and treatment of MDR TB.

Background: Linezolid is a new antibiotic with activity against Mycobacterium tuberculosis in vitro and in animal studies. Several small case series suggest that linezolid is poorly tolerated because of the side effects of anemia/thrombocytopenia and peripheral neuropathy. To characterize our clinical experience with linezolid, the California Department of Public Health Tuberculosis Control Branch's Multidrug-Resistant Tuberculosis (MDR-TB) Service reviewed cases in which the MDR-TB treatment regimens included linezolid therapy., Methods: Record review was performed for 30 patients treated with linezolid as part of an MDR-TB regimen. Data were collected on clinical and microbiological characteristics, linezolid tolerability, and treatment outcomes. The dosage of linezolid was 600 mg daily. Vitamin B6 at a dosage of 50-100 mg daily was used to mitigate hematologic toxicity., Results: During 2003-2007, 30 patients received linezolid for the treatment of MDR-TB. Patients had isolates resistant to a median of 5 drugs (range, 2-13 drugs). Of the 30 cases, 29 (97%) were pulmonary; of these 29, 21 (72%) had positive results of acid-fast bacilli smear, and 16 (55%) were cavitary. Culture conversion occurred in all pulmonary cases at a median of 7 weeks. At data censure (31 December 2008), 22 (73%) of 30 patients had successfully completed treatment. Five continued to receive treatment. There were no deaths. Three patients had a poor outcome, including 2 defaults and 1 treatment failure. Side effects occurred in 9 patients, including peripheral and optic neuropathy, anemia/thrombocytopenia, rash, and diarrhea. However, only 3 patients stopped linezolid treatment because of side effects., Conclusions: Linezolid was well tolerated, had low rates of discontinuation, and may have efficacy in the treatment of MDR-TB.

Extensively drug-resistant (XDR)-TB, defined as TB with resistance to at least isoniazid, rifampin, a fluoroquinolone and either amikacin, kanamycin or capreomycin, is a stark setback for global TB control. Overburdened public-health systems with inadequate resources for case detection and management and high HIV coinfection rates in many regions have contributed to the emergence of XDR-TB. Patients with XDR-TB have poor outcomes, prolonged infectious periods and limited treatment options. To prevent an epidemic of untreatable XDR-TB, improvements in XDR-TB surveillance, increased laboratory capacity for rapid detection of drug-resistant strains, better infection control and the development of new therapeutics are urgently needed.

Chemotherapy of tuberculosis caused by multiple-drug-resistant (MDR) strains is problematic because of choices limited to relatively inefficacious and toxic drugs. Some beta-lactam antibiotics are active against Mycobacterium tuberculosis in vitro. We investigated the efficacy of imipenem in a mouse model of tuberculosis and in humans with MDR tuberculosis. Mice infected with M. tuberculosis strain H37Rv were treated with isoniazid or imipenem. Residual organisms in lung and spleen and survival of imipenem-treated mice were compared to those of untreated or isoniazid-treated mice. Ten patients with MDR tuberculosis also were treated with imipenem in combination with other first- or second-line agents; elimination of M. tuberculosis from sputum samples was measured by quantitative culture. Although it was less effective than isoniazid, imipenem significantly reduced the numbers of M. tuberculosis organisms in lungs and spleens and improved survival of mice. Eight of 10 patients with numerous risk factors for poor outcomes responded to imipenem combination therapy with conversion of cultures to negative. Seven remained culture-negative off of therapy. There were two deaths, one of which was due to active tuberculosis. Organisms were eliminated from the sputa of responders at a rate of 0.35 log10 CFU/ml/week. Relapse upon withdrawal of imipenem and development of resistance to imipenem in a nonresponder suggest that imipenem exerts antimycobacterial activity in humans infected with M. tuberculosis. Imipenem had antimycobacterial activity both in a mouse model and in humans at high risk for failure of treatment for MDR tuberculosis.

Background: To decrease tuberculosis case rates and cases due to recent infection (clustered cases) in San Francisco, California, tuberculosis control measures were intensified beginning in 1991 by focusing on prevention of Mycobacterium tuberculosis transmission and on the use of preventive therapy., Objective: To describe trends in rates of tuberculosis cases and clustered cases in San Francisco from 1991 through 1997., Design: Population-based study., Setting: San Francisco, California., Patients: Persons with tuberculosis diagnosed between 1 January 1991 and 31 December 1997., Measurements: DNA fingerprinting was performed. During sequential 1-year intervals, changes in annual case rates per 100,000 persons for all cases, clustered cases (cases with M. tuberculosis isolates having identical fingerprint patterns), and cases in specific subgroups with high rates of clustering (persons born in the United States and HIV-infected persons) were examined., Results: Annual tuberculosis case rates peaked at 51.2 cases per 100,000 persons in 1992 and decreased significantly thereafter to 29.8 cases per 100,000 persons in 1997 (P < 0.001). The rate of clustered cases decreased significantly over time in the entire study sample (from 10.4 cases per 100,000 persons in 1991 to 3.8 cases per 100,000 persons in 1997 [P < 0.001]), in persons born in the United States (P < 0.001), and in HIV-infected persons (P = 0.003)., Conclusions: The rates of tuberculosis cases and clustered tuberculosis cases decreased both overall and among persons in high-risk groups. This occurred in a period during which tuberculosis control measures were intensified.

Setting: San Francisco, California., Objectives: To identify the characteristics of persons in whom tuberculosis was diagnosed after death, and determine whether secondary cases of tuberculosis resulted from them., Design: Retrospective review of all cases of tuberculosis reported in San Francisco from 1986 through 1995, combined with a prospective evaluation of the molecular epidemiology of tuberculosis., Results: Four per cent of the reported 3102 tuberculosis cases were diagnosed after death. The rate of tuberculosis cases diagnosed after death was 1.63 per 100000 population. Age 43 years or older, male sex, white race, and birth in the United States were characteristics independently associated with a diagnosis of tuberculosis after death. During 1993-1995, injecting drug use was also independently associated with a diagnosis of tuberculosis after death (odds ratio 9.24, 95% confidence interval 1.77-39.38). Cases of tuberculosis diagnosed after death do not appear to be significant sources of undetected tuberculosis transmission causing new secondary tuberculosis cases in the community., Conclusions: Health care providers in San Francisco, and probably other urban areas, should maintain a high index of suspicion for tuberculosis in ageing, white, US-born males, and injecting drug users.

To determine the factors contributing to tuberculosis incidence in the U.S.-born and foreign-born populations in San Francisco, California, and to assess the effectiveness of tuberculosis control efforts in these populations, we performed a population-based molecular epidemiologic study using 367 patients with strains of Mycobacterium tuberculosis recently introduced into the city. IS6110-based and PGRS-based restriction fragment length polymorphism (RFLP) analyses were performed on M. tuberculosis isolates. Patients whose isolates had identical RFLP patterns were considered a cluster. Review of public health and medical records, plus patient interviews, were used to determine the likelihood of transmission between clustered patients. None of the 252 foreign-born cases was recently infected (within 2 yr) in the city. Nineteen (17%) of 115 U. S.-born cases occurred after recent infection in the city; only two were infected by a foreign-born patient. Disease from recent infection in the city involved either a source or a secondary case with human immunodeficiency virus (HIV) infection, homelessness, or drug abuse. Failure to identify contacts accounted for the majority of secondary cases. In San Francisco, disease from recent transmission of M. tuberculosis has been virtually eliminated from the foreign-born but not from the U.S.-born population. An intensification of contact tracing and screening activities among HIV-infected, homeless, and drug-abusing persons is needed to further control tuberculosis in the U.S.-born population. Elimination of tuberculosis in both the foreign-born and the U.S. -born populations will require widespread use of preventive therapy.

Contact tracing, the evaluation of persons who have been in contact with patients having tuberculosis, is an important component of tuberculosis control. We used DNA fingerprinting to test the assumption that tuberculosis in contacts to active cases represents transmission from that person. Cases of tuberculosis in San Francisco between 1991 and 1996 with positive cultures who had been previously identified as contacts ("contact cases") to active cases ("index cases") were studied. Of 11,211 contacts evaluated, there were 66 pairs of culture-positive index and contact cases. DNA fingerprints were available for both members of these pairs in 54 instances (82%). The index and contact cases were infected with the same strain of Mycobacterium tuberculosis in 38 instances (70%; 95% CI: 56 to 82%); 16 pairs (30%) were infected with unrelated strains. Unrelated infections were more common among foreign-born (risk ratio [RR] = 5.22, p < 0.001), particularly Asian (RR = 3.89, p = 0.002) contacts. Contact investigation is an imperfect method for detecting transmission of M. tuberculosis, particularly in foreign-born persons. However, because such investigations target a group with a high prevalence of tuberculosis and tuberculous infection, these efforts remain an important activity in the control of tuberculosis.

Background: Overseas screening of immigrants and refugees applying for a visa to the United States identifies foreign-born individuals who are at high risk for tuberculosis (TB) or who have active TB. The system's effectiveness relies on further medical evaluation and follow-up of foreign-born individuals after their arrival in the United States., Methods: Retrospective cohort study of 893 immigrants and refugees who arrived in the United States from July 1, 1992, through December 31, 1993, with a destination of San Francisco, Calif, and a referral for further medical evaluation., Main Outcome Measures: Time to report to the local health department after arrival and the yield of active and preventable cases of TB from follow-up medical evaluations., Results: Median time from arrival in the United States to seeking care in San Francisco was 9 days (range, 1-920 days). Of 745 immigrants and refugees (83.4%) who sought further medical evaluation, 51 (6.9%) had active TB and 296 (39.7%) were candidates for preventive therapy. Being a refugee was an independent predictor of failure to seek further medical evaluation in the United States. Class B-1 disease status based on overseas TB screening (odds ratio, 3.5; 95% confidence interval, 2.0-6.2) and being from mainland China (odds ratio, 4.4; 95% confidence interval, 1.9-9.9) were independent predictors of TB diagnosed in San Francisco., Conclusions: Timely, adequate medical evaluation and follow-up care of immigrants and refugees has a relatively high yield and should be a high priority for TB prevention and control programs.

Between 1990 and 1994, we conducted a prospective study in five methadone maintenance clinics in San Francisco to determine the rate of tuberculosis (TB) in injection drug users, including those who were anergic. Of the 1,745 persons seen in the clinics, 1,109 completed an evaluation that included skin testing with tuberculin and at least two other antigens (mumps, tetanus, and/or Candida), as well as HIV testing. All persons with a positive tuberculin skin test (TST) and anergic individuals who had radiographic evidence of tuberculous infection (i.e., calcified granulomas) were offered isoniazid (INH) preventive therapy. The median follow-up was 22.0 mo. There were 338 (30.5%) human immunodeficiency virus (HIV)-seropositive patients and 771 (69.5%) HIV-seronegative patients; 96 (28.0%) and 336 (44.0%), respectively, had positive TSTs. Of the HIV-seropositive subjects, 108 (31.9%) had no reaction to any of the three antigens, and were therefore classified as anergic. The rate of TB among the HIV-seropositive, TST-positive patients who did not take INH preventive therapy was 5.0 per 100 person-yr, compared with 0.4 per 100 person-yr among the HIV-seronegative, TST-positive patients (p = 0.007). There were no cases of TB among the anergic subjects. These data indicate that INH preventive therapy is not routinely indicated in anergic, HIV-seropostive patients.

Setting: San Francisco, California., Objective: To determine the relative contributions of infection acquired in San Francisco and reactivation of tuberculous infection acquired elsewhere in Mexican-born persons who developed tuberculosis in San Francisco, and to determine the frequency of transmission leading to secondary cases of tuberculosis in other persons., Design: The study population consisted of all Mexican-born tuberculosis patients reported in San Francisco from 1991 through June 1995. All patients had positive cultures for Mycobacterium tuberculosis and DNA fingerprinting of isolates using IS6110 with more than two bands. Patients were classified as infected in San Francisco or infected elsewhere based on pre-defined criteria that included a second DNA fingerprinting technique (polymorphic guanine-cytosine-rich sequence), chart reviews, and selected patient interviews., Results: Of the 43 Mexican-born patients studied, nine (21%) met the definition of infection acquired in San Francisco and 34 (79%) met the definition of reactivation of infection acquired elsewhere. Only one of the 43 cases resulted in two secondary cases in US-born persons., Conclusion: One-fifth of the Mexican-born patients who developed tuberculosis in San Francisco acquired their tuberculous infection in San Francisco; transmission from Mexican-born persons leading to tuberculosis in other persons is uncommon.

DOT is challenging, rewarding, and the best way we have of ensuring patients' adherence to treatment. Although labor intensive, the team approach with well-defined roles for the RN, DCI, and outreach worker is efficient and effective. Although the human touch-a welcoming, tolerant, and caring approach to the patient-is the single key element, the use of incentives and enablers makes DOT more attractive to patients and the program more successful. An organized approach is necessary, yet flexibility must be maintained. Each patient has unique needs. Using other programs to help, such as school-based nurserun clinics or methadone sites, is more convenient for the patient and increases adherence. Helping patients access other services is important. And, finally, recognizing and appreciating the hard work and skills of the DOT staff contribute to maintaining high staff morale and esprit de corps.

Background: The increasing incidence of tuberculosis caused by drug-resistant Mycobacterium tuberculosis is thought in part to reflect inadequate implementation of standard tuberculosis control measures. However, in San Francisco, USA, which has an effective tuberculosis control programme, we have recently observed an increase in cases of acquired drug-resistance., Methods: To explore further this observation, we analysed the secular trend of acquired drug-resistance and conducted a population-based case-control study of all reported tuberculosis cases in the city of San Francisco between 1985 and 1994., Findings: We identified 14 patients with tuberculosis caused by fully susceptible M tuberculosis who subsequently developed drug-resistance. Of these acquired drug-resistance cases, two occurred between 1985 and 1989, whereas 12 occurred between 1990 and 1994 (p = 0.028). In the case-control study, AIDS (odds ratio 20.2, 95% CI 1.12-363.6), non-compliance with therapy (19.7, 1.66-234.4), and gastrointestinal symptoms (11.5, 1.23-107.0) were independently associated with acquired drug-resistance. Between 1990 and 1994, one in 16 tuberculosis patients with AIDS and either gastrointestinal symptoms or non-compliance developed acquired drug- resistance., Interpretation: The substantial increase in acquired drug- resistance in San Francisco seems to be a product of the increasing prevalence of HIV/M tuberculosis coinfection. Our data suggest that the interface of the HIV and tuberculosis epidemics fosters acquired drug-resistance, and that traditional tuberculosis control measures may not be sufficient in communities with high rates of HIV infection.

Background: The epidemiology of tuberculosis in urban populations is changing. Combining conventional epidemiologic techniques with DNA fingerprinting of Mycobacterium tuberculosis can improve the understanding of how tuberculosis is transmitted., Methods: We used restriction-fragment-length polymorphism (RFLP) analysis to study M. tuberculosis isolates from all patients reported to the tuberculosis registry in San Francisco during 1991 and 1992. These results were interpreted along with clinical, demographic, and epidemiologic data. Patients infected with the same strains were identified according to their RFLP patterns, and patients with identical patterns were grouped in clusters. Risk factors for being in a cluster were analyzed., Results: Of 473 patients studied, 191 appeared to have active tuberculosis as a result of recent infection. Tracing of patients' contacts with the use of conventional methods identified links among only 10 percent of these patients. DNA fingerprinting, however, identified 44 clusters, 20 of which consisted of only 2 persons and the largest of which consisted of 30 persons. In patients under 60 years of age, Hispanic ethnicity (odds ratio, 3.3; P = 0.02), black race (odds ratio, 2.3; P = 0.02), birth in the United States (odds ratio, 5.8; P < 0.001), and a diagnosis of the acquired immunodeficiency syndrome (odds ratio, 1.8; P = 0.04) were independently associated with being in a cluster. Further study of patients in clusters confirmed that poorly compliant patients with infectious tuberculosis have a substantial adverse effect on the control of this disease., Conclusions: Despite an efficient tuberculosis-control program, nearly a third of new cases of tuberculosis in San Francisco are the result of recent infection. Few of these instances of transmission are identified by conventional contact tracing.

A large number of patients with coexisting tuberculosis and HIV infection has been reported. The chest radiographic findings are well described and primarily consist of bilateral, medium-to-coarse reticulonodular opacities often associated with hilar and mediastinal adenopathy. The evolution of chest radiographic abnormalities following treatment for tuberculosis in patients with HIV infection has not been previously studied. Initial and follow-up chest films of 33 patients with tuberculosis and HIV infection were evaluated. All 25 patients whose only pulmonary infection was tuberculosis exhibited radiographic improvement after appropriate treatment. In 8 patients, the chest radiograph worsened while on tuberculosis therapy. In each of these individuals, a newly acquired nontuberculous pulmonary disease was diagnosed as the cause of radiographic deterioration. We conclude that chest radiographs in patients with tuberculosis and HIV-infection will improve with appropriate tuberculosis therapy. Worsening of the chest radiograph does not suggest a poor therapeutic response, but instead indicates the presence of another pulmonary disease.

Background: Tuberculosis typically develops from a reactivation of latent infection. Clinical tuberculosis may also arise from a primary infection, and this is thought to be more likely in persons infected with the human immunodeficiency virus (HIV). However, the relative importance of these two pathogenetic mechanisms in this population is unclear., Methods: Between December 1990 and April 1991, tuberculosis was diagnosed in 12 residents of a housing facility for HIV-infected persons. In the preceding six months, two patients being treated for tuberculosis had been admitted to the facility. We investigated this outbreak using standard procedures plus analysis of the cultured organisms with restriction-fragment-length polymorphisms (RFLPs)., Results: Organisms isolated from all 11 of the culture-positive residents had similar RFLP patterns, whereas the isolates from the 2 patients treated for tuberculosis in the previous six months were different strains. This implicated the first of the 12 patients with tuberculosis as the source of this outbreak. Among the 30 residents exposed to possible infection, active tuberculosis developed in 11 (37 percent), and 4 others (13 percent) had newly positive tuberculin skin tests. Of 28 staff members with possible exposure, at least 6 had positive tuberculin-test reactions, but none had tuberculosis., Conclusions: Newly acquired tuberculous infection in HIV-infected patients can spread readily and progress rapidly to active disease. There should be heightened surveillance for tuberculosis in facilities where HIV-infected persons live, and investigation of contacts must be undertaken promptly and be focused more broadly than is usual.

Background and Methods: Infection with the human immunodeficiency virus (HIV) increases the risk of tuberculosis and may interfere with the effectiveness of antituberculosis chemotherapy. To examine the outcomes in patients with both diagnoses, we conducted a retrospective study of all 132 patients listed in both the acquired immunodeficiency syndrome (AIDS) and tuberculosis case registries in San Francisco from 1981 through 1988., Results: At the time of the diagnosis of tuberculosis, 78 patients (59 percent) did not yet have a diagnosis of AIDS, 18 patients (14 percent) were given a concomitant diagnosis of AIDS (as determined by the presence of an AIDS-defining disease other than tuberculosis), and the remaining 36 patients (27 percent) already had AIDS. The manifestations of tuberculosis were entirely pulmonary in 50 patients (38 percent), entirely extrapulmonary in 40 patients (30 percent), and both pulmonary and extrapulmonary in 42 patients (32 percent). The treatment regimens were as follows: isoniazid and rifampin supplemented by ethambutol for the first two months, 52 patients; isoniazid and rifampin supplemented by pyrazinamide and ethambutol for the first two months, 39 patients; isoniazid and rifampin, 13 patients; isoniazid and rifampin supplemented by pyrazinamide for the first two months, 4 patients; and other drug regimens, 17 patients. The intended duration of treatment for patients whose regimen included pyrazinamide was six months, and for patients who did not receive pyrazinamide, nine months. Seven patients received no treatment because tuberculosis was first diagnosed after death. Sputum samples became clear of acid-fast organisms after a median of 10 weeks of therapy. Abnormalities on all chest radiographs taken after three months of treatment were stable or improved except for those of patients who had new nontuberculous infections. The only treatment failure occurred in a man infected with multiple drug-resistant organisms who did not comply with therapy. Adverse drug reactions occurred in 23 patients (18 percent). For all 125 treated patients, median survival was 16 months from the diagnosis of tuberculosis. Tuberculosis was a major contributor to death in 5 of the 7 untreated patients and 8 of the 125 treated patients. Three of 58 patients who completed therapy had a relapse (5 percent); compliance was poor in all 3., Conclusions: Tuberculosis causes substantial mortality in patients with advanced HIV infection. In patients who comply with the regimen, conventional therapy results in rapid sterilization of sputum, radiographic improvement, and low rates of relapse.

Human immunodeficiency virus (HIV) serology was performed in non-Asian-born patients 18-65 years old with newly diagnosed tuberculosis at a county tuberculosis clinic, and demographic and clinical features of HIV-seropositive and HIV-seronegative patients were compared. Sixty of 128 eligible patients agreed to participate, of whom 17 (28%) were seropositive. Risk of HIV was associated with homosexual contact, intravenous drug use, or both; however, 4 (24%) of the 17 seropositives denied risk behaviors. Significantly more blacks (48%) than whites (10%) or Latinos (20%) were HIV-seropositive (P less than .01). Site of disease, tuberculin reactivity, response to therapy, drug toxicity, and relapse did not differ significantly between groups. HIV-seropositive patients had significantly lower median CD4+ cell counts (326/mm3, range 23-742/mm3, vs. 929/mm3, range 145-2962/mm3, P less than .0005) and median CD4+:CD8+ ratios (0.50, range 0.14-1.07 vs. 1.54, range 0.35-4.36, P less than .0001). HIV infection is associated with clinically typical tuberculosis and HIV screening of tuberculosis patients is recommended in areas where HIV is endemic.

The outcome of treatment for pulmonary tuberculosis using isoniazid and rifampin for 9 months supplemented by ethambutol for the initial 2 months was evaluated in a cohort of 233 patients. All patients had sputum cultures positive for Mycobacterium tuberculosis sensitive to isoniazid and rifampin. Of the 233 patients, 200 completed the regimen without change. Four patients had adverse reactions necessitating discontinuation and four became pregnant and had ethambutol substituted for rifampin. All eight were treated successfully with altered regimens. Ten patients were lost to follow-up, seven died, and eight were transferred to other jurisdictions. No patients failed to convert their sputum during therapy. At completion of therapy, three patients (1.5%) were found to have positive sputum. Follow-up 6 months after completion of treatment in 174 successfully treated patients revealed four (2.3%) with positive sputum. No further relapses were detected on evaluation 12 months after treatment was completed. All seven patients who failed therapy or relapsed were retreated successfully using the same regimen. These data provide a reference standard against which newer treatment regimens, such as the 6-month regimen currently in use, can be compared. In addition, the value of routine evaluations in detecting relapses at the time treatment is completed and 6 months later was substantiated, but 12-month follow-up was not useful.

Tuberculosis has been reported previously in patients with acquired immunodeficiency syndrome who are at increased risk of prior infection with Mycobacterium tuberculosis. We performed a population-based study of AIDS and tuberculosis in San Francisco using the Tuberculosis and AIDS Registries of the San Francisco Department of Public Health. Of 287 cases of tuberculosis in non-Asian-born males 15 to 60 yr of age reported from 1981 through 1985, 35 (12%) also had AIDS, including 23 American-born whites. Patients with tuberculosis and AIDS were more likely to be nonwhite and heterosexual intravenous drug users than were AIDS patients without tuberculosis. Fifty-one percent had tuberculosis diagnosed before AIDS, and 37 percent had AIDS diagnosed at least 1 month prior to the diagnosis of tuberculosis. Although the lungs were the most frequent site of tuberculosis in both AIDS and non-AIDS patients, 60% of the AIDS group had at least 1 extrapulmonary site of disease compared to 28% of the non-AIDS group (p less than 0.001). Nonsignificant tuberculin skin tests were more common in AIDS patients (14 of 23 patients tested) than in non-AIDS patients (12 of 129 patients tested; p less than 0.0001). Chest radiographs in AIDS patients showed predominantly diffuse or miliary infiltrates (60%), whereas non-AIDS patients had predominantly focal infiltrates and/or cavitation (68%). Response to antituberculosis therapy was favorable in AIDS patients, although adverse drug reactions occurred more frequently than in non-AIDS patients (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)