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.