RESUMO
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.
Assuntos
Falência Renal Crônica/epidemiologia , Tuberculose/epidemiologia , Adolescente , Adulto , Idoso , California/epidemiologia , Criança , Pré-Escolar , Comorbidade , Feminino , Humanos , Incidência , Lactente , Falência Renal Crônica/complicações , Masculino , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Vigilância da População , Resultado do Tratamento , Tuberculose/complicações , Tuberculose/terapia , Adulto JovemRESUMO
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.
Assuntos
Técnicas de Diagnóstico Molecular/métodos , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Resistente a Múltiplos Medicamentos/diagnóstico , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Adulto , Antituberculosos/farmacologia , Antituberculosos/uso terapêutico , California , Diagnóstico Precoce , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Mycobacterium tuberculosis/genética , Estudos Retrospectivos , Fatores de TempoRESUMO
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.
Assuntos
Antibióticos Antituberculose/farmacologia , RNA Polimerases Dirigidas por DNA/genética , Mutação de Sentido Incorreto , Mycobacterium tuberculosis/efeitos dos fármacos , Rifabutina/farmacologia , Rifampina/farmacologia , Tuberculose/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/enzimologia , Mycobacterium tuberculosis/genética , Mycobacterium tuberculosis/isolamento & purificaçãoRESUMO
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.
Assuntos
Infecção Hospitalar/prevenção & controle , DNA Bacteriano/análise , Técnicas de Apoio para a Decisão , Controle de Infecções/métodos , Mycobacterium tuberculosis/isolamento & purificação , Técnicas de Amplificação de Ácido Nucleico , Tuberculose Pulmonar/diagnóstico , Infecção Hospitalar/epidemiologia , Humanos , Mycobacterium tuberculosis/genética , Sensibilidade e Especificidade , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/prevenção & controle , Estados Unidos/epidemiologiaRESUMO
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.
Assuntos
Avaliação Geriátrica/estatística & dados numéricos , Instituição de Longa Permanência para Idosos/tendências , Casas de Saúde/tendências , Tuberculose/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , California/epidemiologia , Busca de Comunicante/estatística & dados numéricos , Feminino , Humanos , Incidência , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Mycobacterium tuberculosis/isolamento & purificação , Estudos Retrospectivos , Tuberculose/diagnósticoRESUMO
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.
Assuntos
Antituberculosos/farmacologia , Tuberculose Extensivamente Resistente a Medicamentos , Saúde Global , Mycobacterium tuberculosis/efeitos dos fármacos , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/microbiologia , Antituberculosos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/genética , Tuberculose Extensivamente Resistente a Medicamentos/tratamento farmacológico , Tuberculose Extensivamente Resistente a Medicamentos/epidemiologia , Tuberculose Extensivamente Resistente a Medicamentos/microbiologia , Infecções por HIV/complicações , Humanos , Testes de Sensibilidade Microbiana , Mycobacterium tuberculosis/classificação , Mycobacterium tuberculosis/genética , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/microbiologiaRESUMO
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.