A lack of detectable fitness cost of trimethoprim resistance in vitro together with a strong co-selection of other antibiotics could explain the rather disappointing effect of the intervention. The result emphasizes the low possibility of reverting antibiotic resistance once established and the urgent need for the development of new antibacterial agents.

Using data from an ongoing Swedish intervention project, the observed durations of nasopharyngeal carriage of penicillin-nonsusceptible Streptococcus pneumoniae (PNSP) (MIC of penicillin G of >0.5 g/ml) stratified by both pneumococcal serogroup and age of the carrier were compared. The means and 95% confidence intervals (CIs) were estimated by fitting a gamma distribution to the observed duration of carriage for each age and serogroup stratum. The mean observed duration of carriage for all cases was 37 days (95% CI, 35 to 38 days). Children below the age of 5 years carried PNSP for significantly longer periods (43 days; 95% CI, 41 to 45 days) compared with older individuals (25 days; 95% CI, 24 to 27 days). There were also differences within the group of cases below the age of 5 years, as the duration of carriage became significantly shorter for each increasing age step: <1, 1 to 2, and 3 to 4 years. In addition, patients <5 years of age carried serogroups 9 and 14 for significantly shorter periods than groups 6 and 23. Serogroup 9 was also carried for significantly shorter periods than group 19. For patients aged 5 years or older, no significant difference in carriage duration for different ages or serogroups could be noted. As young children have the longest duration of PNSP carriage, interventions aiming to reduce the prevalence in this group are of great importance. The results highlight the importance of taking both serogroup and age of the carriers into account when studying the dynamics of pneumococcal transmission in young children.Nasopharyngeal carriage is an important feature in the epidemiology of Streptococcus pneumoniae (the pneumococcus). Colonization precedes the development of disease in the individual (9, 11), and the nasopharynx acts as the main reservoir from which the bacteria are spread between individuals in the community (3, 4). As high penicillin resistance levels are reported in pneumococci today (13), modeling trends and evaluating the effect of interventions are of great interest. Since prevalence is a composite of both the incidence and the duration of carriage, an understanding of this relationship requires a separation of the two components.Large variations in the duration of nasopharyngeal pneumococcal carriage have been observed. Age has been reported to be an important determinant, with the longest duration of carriage seen in the youngest individuals (7,19,25). Previous studies have also shown that serogroups 6, 19, and 23 are carried for longer periods than other serogroups (11, 25). However, as these serogroups are more common among the youngest children, age-related bias cannot be excluded (7). To our knowledge, durations of carriage adjusted for both the age of the carrier and the pneumococcal serogroup in order to avoid this bias have not been described previously.In the Skåne Region of Sweden, all identified cases of pneumococci with an MIC to penicillin G (PcG) of Ն0.5 g/ml (designated penicillin-nonsusceptible Streptococcus pneumoniae [PNSP]) are monitored with repeated...

Historically, antibiotic treatment guidelines have aimed to maximize treatment efficacy and minimize toxicity, but have not considered the evolution of antibiotic resistance. Optimizing the duration and dosing of treatment to minimize the duration of symptomatic infection and selection pressure for resistance simultaneously has the potential to extend the useful therapeutic life of these valuable life-saving drugs without compromising the interests of individual patients.Here, using mathematical models, we explore the theoretical basis for shorter durations of treatment courses, including a range of ecological dynamics of bacteria that cause infections or colonize hosts as commensals. We find that immunity is an important mediating factor in determining the need for long duration of treatment. When immunity to infection is expected, shorter durations that reduce the selection for resistance without interfering with successful clinical outcome are likely to be supported. Adjusting drug treatment strategies to account for the impact of the differences in the ecological niche occupied by commensal flora relative to invasive bacteria could be effective in delaying the spread of bacterial resistance.