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ObjectivesHousehold contacts (HHCs) of pulmonary tuberculosis patients are at high risk of Mycobacterium tuberculosis infection and early disease development. Identification of individuals at risk of tuberculosis disease is a desirable goal for tuberculosis control. Interferon-gamma release assays (IGRAs) using specific M. tuberculosis antigens provide an alternative to tuberculin skin testing (TST) for infection detection. Additionally, the levels of IFNγ produced in response to these antigens may have prognostic value. We estimated the prevalence of M. tuberculosis infection by IGRA and TST in HHCs and their source population (SP), and assessed whether IFNγ levels in HHCs correlate with tuberculosis development.MethodsA cohort of 2060 HHCs was followed for 2–3 years after exposure to a tuberculosis case. Besides TST, IFNγ responses to mycobacterial antigens: CFP, CFP-10, HspX and Ag85A were assessed in 7-days whole blood cultures and compared to 766 individuals from the SP in Medellín, Colombia. Isoniazid prophylaxis was not offered to child contacts because Colombian tuberculosis regulations consider it only in children under 5 years, TST positive without BCG vaccination.ResultsUsing TST 65.9% of HHCs and 42.7% subjects from the SP were positive (OR 2.60, p<0.0001). IFNγ response to CFP-10, a biomarker of M. tuberculosis infection, tested positive in 66.3% HHCs and 24.3% from the SP (OR = 6.07, p<0.0001). Tuberculosis incidence rate was 7.0/1000 person years. Children <5 years accounted for 21.6% of incident cases. No significant difference was found between positive and negative IFNγ responders to CFP-10 (HR 1.82 95% CI 0.79–4.20 p = 0.16). However, a significant trend for tuberculosis development amongst high HHC IFNγ producers was observed (trend Log rank p = 0.007).DiscussionCFP-10-induced IFNγ production is useful to establish tuberculosis infection prevalence amongst HHC and identify those at highest risk of disease. The high tuberculosis incidence amongst children supports administration of chemoprohylaxis to child contacts regardless of BCG vaccination.

The agar dilution, broth microdilution, and disk diffusion methods were compared to determine the in vitro susceptibility of 428 extended-spectrum-␤-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae to fosfomycin. Fosfomycin showed very high activity against all ESBL-producing strains. Excellent agreement between the three susceptibility methods was found for E. coli, whereas marked discrepancies were observed for K. pneumoniae.Fosfomycin tromethamine is a stable salt of fosfomycin which is licensed for the single-dose treatment of acute uncomplicated urinary tract infections (UTIs) caused by susceptible organisms (8,12). After many years of fosfomycin use, both in Spain and worldwide, fosfomycin continues to be active against the most common uropathogens, and there is a very low incidence of resistant strains in Escherichia coli (about 2%) (2,12,14).Isolation of extended-spectrum-␤-lactamase (ESBL)-producing E. coli and Klebsiella pneumoniae strains is increasing in Spain, and a high proportion of these isolates are recovered from outpatients with uncomplicated UTIs (4, 7, 11). It is common to find that the same plasmid coding for ESBL also contains genes conferring resistance to several groups of antimicrobial agents, such as aminoglycosides and cotrimoxazole (7, 10). The concurrence of quinolone resistance, particularly in ESBL-producing K. pneumoniae, is frequent (6, 10, 13), there being few alternatives for the appropriate oral treatment of uncomplicated UTIs caused by ESBL-producing microorganisms.The present study was designed to assess the in vitro activity of fosfomycin by three different methods against 428 ESBLproducing strains, made up of 290 (68%) E. coli and 138 (32%) K. pneumoniae isolates.The strains were collected in two Spanish studies: the first, developed in 2000, included 40 hospitals representing different regions of Spain, and the second was carried out in Seville, Spain, at the University Hospital of Virgen Macarena (UHVM), using strains recovered between 1995 and 2001 (7, 11). In both studies ESBL production was determined by broth microdilution according to CLSI guidelines (5).The strains collected from the multicenter study included 170 E. coli and 70 K. pneumoniae strains, while those obtained from the UHVM included 120 E. coli and 68 K. pneumoniae strains. One-hundred thirty-two out of 290 (45.5%) E. coli and 16 out of 138 (11.6%) K. pneumoniae strains were isolated from outpatients with community-acquired infections, and among these isolates found in the community, 66 (22.7%) E. coli and 9 (6.5%) K. pneumoniae strains were isolated from urine samples of women with uncomplicated UTIs.The MICs of fosfomycin (Zambon, Milan, Italy) were determined by the agar dilution and broth microdilution methods in cation adjusted Mueller-Hinton medium, supplemented with 25 mg/liter of G-6-P (glucose-6-phosphate; Sigma Chemical Co.). A twofold dilution across a range of 0.25 to 512 mg of fosfomycin per liter was used. The inocula were prepared to achieve 1 ϫ 10 4 CFU per spot (ag...