Trends in mortality and antibiotic resistance among HIV-infected patients with invasive pneumococcal disease.

OBJECTIVES: The aim of the study was to describe trends and risk factors for mortality and changes in antibiotic resistance, serotypes and clones among HIV-infected patients with invasive pneumococcal disease (IPD).
METHODS: A prospective study of 199 episodes of IPD occurring in a cohort of 4011 HIV-infected patients was carried out. Predictors of mortality included clinical and microbiological data. The 7-valent pneumococcal conjugate vaccine (PCV7) for children was introduced in late 2001. Time periods were classified for mortality studies as pre- (1986-1996), early (1997-2001) and late (2002-2007) highly active antiretroviral therapy (HAART) era, and for serotype studies as pre-PCV7 (1986-2001) and PCV7 (2002-2007) era.
RESULTS: Of 199 IPD episodes, 71 (36%) occurred in HIV-infected patients with associated comorbidities (mainly liver cirrhosis; 52 of 71), which increased in recent years. The incidence of IPD decreased from the pre-HAART era to the early HAART era and then remained stable in the late HAART era (24.1, 8.4 and 7.4 episodes per 1000 patient-years, respectively). Rates of 30-day mortality have risen over the three periods (8, 19 and 25%, respectively; P = 0.017). In multiple logistic regression analysis, predictors of mortality were shock at presentation [odds ratio (OR) 7.01; 95% confidence interval (CI) 2.05-23.87] and associated comorbidities (OR 4.27; 95% CI 1.53-11.92). In the PCV7 era, IPD caused by non-PCV7 serotypes increased, and resistance to betalactams decreased. The most frequent genotypes were Spain(9V)-ST156, Spain(23F)-ST81, ST88(19F), Sweden(1)-ST304 and Spain(6B)-ST90.
CONCLUSIONS: In the late HAART era, the incidence of IPD has not significantly decreased. Mortality from IPD has risen in association with an increase in comorbidities such as liver cirrhosis. New vaccination strategies are needed to diminish the burden of IPD in the HIV-infected population.