Successes and challenges of latent TB screening and treatment in a high-prevalence US region.

BACKGROUND: South Texas has higher TB disease incidence than much of the United States. We evaluated a multi-site South Texas interferon-gamma release assay (IGRA)-based testing and latent TB infection (LTBI) treatment program targeting high-risk populations.METHODS: Number of IGRA tests, test results, LTBI confirmation, and treatment outcomes were collected over 2.5 years. Sixteen semi-structured patient interviews and 10 site-based focus groups were conducted with providers, nurses, and administrators. Grounded theory identified themes associated with successful outcomes.RESULTS: Of 9,050 IGRA tests, 687 (8%) were positive; 340 (49%) confirmed as LTBI; 191 initiated LTBI treatment; and 130 (68% of initiators) completed treatment. Patient barriers to treatment completion included lack of knowledge, misconceptions, and treatment toxicities. Clinic staff concurred that toxicity was a barrier to treatment and requiring new processes with limited resources were implementation barriers.CONCLUSIONS: Over 9,000 patients were screened with a high prevalence of IGRA positivity, but confirming LTBI, initiating, and completing treatment were challenging. Qualitative evaluation supports low literacy patient education on LTBI and toxicities and expanded support for process implementation and provider training. These findings highlight challenges at all levels of the LTBI care cascade and provide patient, staff, and provider perspectives on implementation of these programs.

Characteristics and costs of multidrug-resistant tuberculosis in-patient care in the United States, 2005-2007.

OBJECTIVE: A population-based study of 135 multidrug-resistant tuberculosis (MDR-TB) patients reported to the Centers for Disease Control and Prevention (CDC) during 2005-2007 found 73% were hospitalized. We analyzed factors associated with hospitalization. METHODS: We assessed statistically significant multivariable associations with US in-patient TB diagnosis, frequency of hospitalization, length of hospital stay, and in-patient direct costs to the health care system. RESULTS: Of 98 hospitalized patients, 83 (85%) were foreign-born. Blacks, diabetics, or smokers were more likely, and patients with disseminated disease less likely, to receive their TB diagnosis while hospitalized. Patients aged ⩾65 years, those with the acquired immune-deficiency syndrome (AIDS), or with private insurance, were hospitalized more frequently. Excluding deaths, length of stay was greater for patients aged ⩾65 years, those with extensively drug-resistant TB (XDR-TB), those residing in Texas, those with AIDS, those who were unemployed, or those who had TB resistant to all first-line medications vs. others. Average hospitalization cost per XDR-TB patient (US$285 000) was 3.5 times that per MDR-TB patient (US$81 000), in 2010 dollars. Hospitalization episode costs for MDR-TB rank third highest and those for XDR-TB highest among the principal diagnoses. CONCLUSIONS: Hospitalization was common and remains a critical care component for patients who were older, had comorbidities, or required complex management due to XDR-TB. MDR-TB in-patient costs are among the highest for any disease.

Disruption of the genes encoding antigen 85A and antigen 85B of Mycobacterium tuberculosis H37Rv: effect on growth in culture and in macrophages.

The mechanism of pathogenesis of Mycobacterium tuberculosis is thought to be multifactorial. Among the putative virulence factors is the antigen 85 (Ag85) complex. This family of exported fibronectin-binding proteins consists of members Ag85A, Ag85B, and Ag85C and is most prominently represented by 85A and 85B. These proteins have recently been shown to possess mycolyl transferase activity and likely play a role in cell wall synthesis. The purpose of this study was to generate strains of M. tuberculosis deficient in expression of the principal members of this complex in order to determine their role in the pathogenesis of M. tuberculosis. Constructs of fbpA and fbpB disrupted with the kanamycin resistance marker OmegaKm and containing varying amounts of flanking gene and plasmid vector sequences were then introduced as linear fragments into H37Rv by electroporation. Southern blot and PCR analyses revealed disruption of the homologous gene locus in one fbpA::OmegaKm transformant and one fbpB::OmegaKm transformant. The fbpA::OmegaKm mutant, LAa1, resulted from a double-crossover integration event, whereas the fbpB::OmegaKm variant, LAb1, was the product of a single-crossover type event that resulted in insertion of both OmegaKm and plasmid sequences. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis confirmed that expression of the disrupted gene was not detectable in the fbpA and fbpB mutants. Analysis of growth rates demonstrated that the fbpB mutant LAb1 grew at a rate similar to that of the wild-type parent in enriched and nutrient-poor laboratory media as well as in human (THP-1) and mouse (J774.1A) macrophage-like cell lines. The fbpA mutant LAa1 grew similarly to the parent H37Rv in enriched laboratory media but exhibited little or no growth in nutrient-poor media and macrophage-like cell lines. The targeted disruption of two genes encoding mycolyl transferase and fibronectin-binding activities in M. tuberculosis will permit the systematic determination of their roles in the physiology and pathogenesis of this organism.

Nosocomial outbreak caused by a multiresistant clone of Acinetobacter baumannii: results of the case-control and molecular epidemiologic investigations.

OBJECTIVE: To describe a nosocomial outbreak caused by multiresistant Acinetobacter baumannii. DESIGN: Descriptive and case-control study. Antibiotic susceptibilities and pulsed-field gel electrophoresis (PFGE) of genomic DNA digested with SfiI and also with ApaI were used as markers of strain identity. SETTING: A large medical school-affiliated hospital in the city of Houston, Texas. RESULTS: During a 10-week period, A baumannii was isolated from 25 patients admitted to the intensive care unit (ICU). The attack rate was 14.3 per 100 ICU admissions. Case patients were intubated more frequently and for longer periods, and had longer ICU and hospital stays (P < 0.05 for each of these characteristics). Multivariate logistic regression analysis identified the length of ICU stay and the use of third-generation cephalosporins as associated with the acquisition of A baumannii. Patients infected with A baumannii had a higher mortality rate than colonized patients and control patients (P < 0.01). Sixteen isolates recovered from these 25 patients were susceptible only to imipenem/cilastatin, and PFGE confirmed that a single clone was the cause of this outbreak. Nine isolates of A baumannii from patients infected or colonized in two other hospitals in Houston during the same period, differed from the outbreak isolates by their susceptibility to ciprofloxacin. However, PFGE results were identical, indicating unsuscepted genetic relatedness among isolates from three different hospitals. CONCLUSIONS: A baumannii is an important nosocomial opportunistic pathogen and can adversely affect the outcome of ICU patients who acquire this organism. This outbreak was caused by a single clone that was isolated concurrently from three hospitals.