Clinically and microbiologically derived azithromycin susceptibility breakpoints for Salmonella enterica serovars Typhi and Paratyphi A.

Azithromycin is an effective treatment for uncomplicated infections with Salmonella enterica serovar Typhi and serovar Paratyphi A (enteric fever), but there are no clinically validated MIC and disk zone size interpretative guidelines. We studied individual patient data from three randomized controlled trials (RCTs) of antimicrobial treatment in enteric fever in Vietnam, with azithromycin used in one treatment arm, to determine the relationship between azithromycin treatment response and the azithromycin MIC of the infecting isolate. We additionally compared the azithromycin MIC and the disk susceptibility zone sizes of 1,640 S. Typhi and S. Paratyphi A clinical isolates collected from seven Asian countries. In the RCTs, 214 patients who were treated with azithromycin at a dose of 10 to 20 mg/ml for 5 to 7 days were analyzed. Treatment was successful in 195 of 214 (91%) patients, with no significant difference in response (cure rate, fever clearance time) with MICs ranging from 4 to 16 µg/ml. The proportion of Asian enteric fever isolates with an MIC of ≤ 16 µg/ml was 1,452/1,460 (99.5%; 95% confidence interval [CI], 98.9 to 99.7) for S. Typhi and 207/240 (86.3%; 95% CI, 81.2 to 90.3) (P < 0.001) for S. Paratyphi A. A zone size of ≥ 13 mm to a 5-µg azithromycin disk identified S. Typhi isolates with an MIC of ≤ 16 µg/ml with a sensitivity of 99.7%. An azithromycin MIC of ≤ 16 µg/ml or disk inhibition zone size of ≥ 13 mm enabled the detection of susceptible S. Typhi isolates that respond to azithromycin treatment. Further work is needed to define the response to treatment in S. Typhi isolates with an azithromycin MIC of >16 µg/ml and to determine MIC and disk breakpoints for S. Paratyphi A.

The influence of HIV infection on clinical presentation, response to treatment, and outcome in adults with Tuberculous meningitis.

BACKGROUND: Tuberculous meningitis occurs more commonly in human immunodeficiency virus (HIV)-infected individuals than in HIV-uninfected individuals, but whether HIV infection alters the presentation and outcome of tuberculous meningitis is unknown. METHODS: We performed a prospective comparison of the presenting clinical features and response to treatment in 528 adults treated consecutively for tuberculous meningitis (96 were infected with HIV and 432 were uninfected with HIV) in 2 tertiary-care referral hospitals in Ho Chi Minh City, Vietnam. Logistic regression was used to model variables associated independently with HIV infection, 9-month survival, and the likelihood of having a relapse or an adverse drug event. Kaplan-Meier estimates were used to compare survival rates and times to fever clearance, coma clearance, relapse, and adverse events. RESULTS: HIV infection did not alter the neurological presentation of tuberculous meningitis, although additional extrapulmonary tuberculosis was more likely to occur in HIV-infected patients. The 9-month survival rate was significantly decreased in HIV-infected patients (relative risk of death from any cause, 2.91 [95% confidence interval, 2.14-3.96]; P < .001), although the times to fever clearance and coma clearance and the number or timing of relapses or adverse drug events were not significantly different between the groups. CONCLUSIONS: HIV infection does not alter the neurological features of tuberculous meningitis but significantly reduces the survival rate.