DISCUSSION
The main value of the current study is that it shows the medium and long-term safety of reducing the duration of antibiotic treatment in patients admitted for a case of CAP, based on clinical stability criteria, without leading to a greater number of long-term complications; nor did it lead to higher mortality or readmission rates, nor differences in the systemic inflammation presented by these patients. That is, the fact that there are no significant long-term differences in the main results under study between the control and intervention groups, validates our proposal to reduce the duration of antibiotic treatment in patients with clinically stable CAP from the point of view of the long-term safety of the patient.
The beneficial effects of reducing the duration of antibiotic treatment have been studied widely. On the one hand, it reduces antimicrobial resistance, possible adverse effects and costs, while, on the other hand, it improves adherence to treatment-6-9. However, despite current evidence, convincing clinicians to avoid unnecessarily prolonged guidelines remains an arduous task, likely due to a false sense of security provided by longer term treatments. In fact, a retrospective study carried out in the United States in patients admitted for CAP, observed that the average duration of antibiotic treatment exceeded the recommended time by 74% and 71% for patients aged 18-64 years and ≥ 65 years, respectively22.
A remarkable strength of this study is that it is based on a clinical trial with a unique design where the doctor him or herself decided on the type of antibiotic and in which similar cure rates were obtained for both groups. Likewise, unlike most of the studies published so far and despite the exclusion of patients requiring admission to Intensive Care, up to 40% of patients with IV and V PSI were included. However, the evidence for critically ill patients is limited. Chastre et al. carried out a double-blind clinical trial in patients with ventilator-associated pneumonia in which they compared 8-day versus 15 day antibiotic regimens23. The authors observed no differences between the two groups except in the case of non-fermenting gram-negative germs. Recently, in a meta-analysis in which they compared regimens of ≤ 6 days versus ≥ 7 days with similar results, they carried out a sub-analysis in patients with severe pneumonia, observing lower mortality in the group with the shorter regimen (2.2% vs. 4.7%)15.
CAP has a great impact on systemic inflammation, both in the short and the long term24. PCT has been the most widely studied biomarker for reducing antibiotic treatment. De Jong et al. conducted a clinical trial in critically ill patients in which the antibiotic was discontinued if the PCT value decreased by at least 80% or below 0.5 ug / L25. The median number of days on antibiotics was 5 in the PCT group versus 7 days in the control group. Furthermore, the 1-year mortality in the PCT group was 36% as opposed to 43% in the control group (absolute difference 7.4, 1.3-13.8, p= 0.0188). However, the biomarker showing the best prognostic power for short and long-term complications in CAP has been proadrenomedullin26-28. To this effect, in our study we were able to obtain a sample for biomarker analysis from 146 patients, without observing differences in biomarker levels between the control and intervention groups.
Mortality at 1 year after a case of CAP is high and it is thought that the cause may lie in a state of persistent chronic inflammation that leads to a greater number of cardiovascular events and higher long-term mortality29-31. Undoubtedly, knowing the kinetics of biomarkers is crucial to measure the evolution of inflammation, proADM being the one biomarker that has shown the best results26,32. For that reason, the evolution of biomarkers from day 5 to day 30 was analyzed, after adjusting for their baseline value, without obtaining significant differences between both groups, which supports the idea that the reduction of antibiotic treatment does not impact systemic inflammation.
Finally, our study has some limitations. First, data collection from 30 days to 1 year was done retrospectively. Second, few complications were observed in the sample with biomarkers, probably due to the small sample size. Third, the results cannot be extrapolated to the excluded population. Future studies assessing patients with those characteristics are necessary.
In conclusion, our study indicates that individualizing and reducing the duration of antibiotic treatment in patients with CAP based on clinical stability criteria is safe, without leading to a greater number of long-term complications or differences in systemic inflammation.
Funding: This study has received the following funding: SEPAR FELLOWSHIP (101/2016 Impact of the duration of antibiotic treatment on the long-term prognosis of patients admitted for community-acquired pneumonia); BBK-BIOCRUCES POST-MIR COURSE 2018-2019- BBK-BC / POST-MIR / 2018/007 FELLOWSHIPS.