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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.

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.

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.

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.

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.