Antimicrobial therapy and adherence to guideline recommendations: Studies on pneumonia and bloodstream infections

Abstract

Effective antimicrobial therapy are a prerequisite for modern medical treatment in all medical specialties. However, overuse of antimicrobial therapy is considered a driver of antimicrobial resistance, which eventually increases the risk of therapy failure and mortality. In general, reasons for overuse are unnecessary, inappropriate or suboptimal antimicrobial prescriptions. In Norway, antimicrobial consumption is generally low compared to European countries, and antimicrobial resistance is among the lowest in the world. Good qualitative studies that emphasize the correct and rational use or possible overuse of antimicrobial therapy are lacking. In this doctoral thesis, I have focused on qualitative studies that can highlight the prescribing of antimicrobial therapy to key infections frequently encountered in hospital settings. We chose community-acquired pneumonia (CAP) and bloodstream infections (BSI) diagnosed and managed in hospital settings as models. Our aim was to establish studies that could provide sufficiently knowledge about qualitative aspects for these infections. We therefore conducted four retrospective, observational studies, of which two on CAP and two on BSI. In the first study, we launched an intervention in the emergency room setting to increase proportions of patients that underwent collection of representative respiratory secretions of expectorate or induced sputum in CAP. The number of patients who completed the test increased significantly. In addition, we observed an increase in diagnostic yield from 41.2 % to 62.0 %. The study showed that relatively modest measures in the emergency room setting could increase the proportions of microbiologically confirmed cases of CAP. In the second study, we investigated whether the proportion of patients prescribed with first-line antimicrobial therapy for CAP could be influenced by a targeted intervention that promoted clinical guideline recommendations. Empiric first-line antimicrobial therapy with narrow-spectrum ϐ-lactams increased significantly from 56.1 % to 74.4 % over the six-year period. The proportion that received broad-spectrum regimens decreased significantly from 34.1 % to 17.1 % in the corresponding period. The study showed that CAP is a suitable model for antimicrobial stewardship measures. In the third study, we retrospectively collected data from 270 patients with culturepositive BSIs in the intensive care setting. In community-acquired BSIs, empirical antimicrobial therapy was concordant on day 0, 1, 2, 3, and 3-9 in 88.0 %, 91.6 %, 94.7 %, 95.2 % and 96.4 %, respectively. However, in hospital-acquired BSIs, such therapy was concordant in only 65.1 %, 74.7 %, 83.5 %, 87.0 %, and 89.3 %. For all days, an association model returned statistically significant differences. Discordant antimicrobial therapy for hospital-acquired BSIs was significantly associated with mortality on day 28. The study showed that empirical antimicrobial therapy for community-acquired BSIs was far more sufficient to cover for the detected pathogen, as compared to hospital-acquired BSIs. In the fourth study, we included all culture-positive BSI episodes throughout an entire calendar year, comprising a total study population of 756 cases. The BSI episodes were mainly managed in ordinary hospital ward settings outside of the ICU. In 70.6 % of episodes, empirical antimicrobial therapy were guideline-adherent, and in 25.1 %, other regimens were chosen. For BSI episodes that received guideline-adherent antimicrobial therapy, 85.5 % were concordant, and 14.2 % were discordant. For BSI episodes that received non-adherent regimens, the corresponding proportions were 73.7 % and 26.3 %, respectively. An association model returned a statistically significant relationship between guideline-adherent antimicrobial therapy and concordance. A mortality-analysis showed that discordant antimicrobial therapy was significantly associated with both intra-hospital and long-term mortality. The study thus provided validation to antimicrobial prescriptions compliant with clinical practice guideline recommendations. The studies have provided valuable insights and knowledge about antimicrobial therapy to key infections at a university hospital in Norway with presumptive low antimicrobial consumption and in low resistance environments. Both diagnostic aspects and empirical and targeted antimicrobial therapies are important factors for the rational use of antimicrobial therapy. This is important for several reasons. Firstly, it can likely be achieved without affecting mortality and morbidity. Secondly, it can be achieved by even modest efforts, for instance by increasing adherence to clinical practice guideline recommendations. Thirdly, it can be achieved even in countries with low antimicrobial usage. And fourthly, it has the potential to reduce antimicrobial usage and thereby suppress drivers of antimicrobial resistance