Discussion
acute cognitive impairment
EVENTS, DISEASE
In this randomised study, adding sputum-POC-PCR to our diagnostic setup did not affect prescriptions of no or narrow-spectrum antibiotics during the first 2 days of admission, but less patients in the POC-PCR-group were treated with no or narrow-spectrum antibiotics after 5 days. Interestingly, patients in the POC-PCR-group were more likely to receive early targeted and adequate treatment. Number of readmissions, ICU admissions, and mortality were unchanged but we found a nonsignificant one-day reduction in LOS. Several prospective studies have reported sputum-POC-PCR as a method to support clinical decisions by fast and accurate detection of CAP pathogens [Our outcomes were different focusing on type of antibiotic instead of length of treatment and route of administration, but nevertheless, the failure of POC-PCR to increase the use of no or narrow-spectrum antibiotics may seem to contrast these previous results.There are some likely explanations. In an international context, the level of antimicrobial resistance is very low in Denmark and most pneumococci and Another possible explanation is the very low prevalence of common respiratory viruses in the study period related to the SARS-CoV-2 pandemic [The increased prescription of targeted and adequate antibiotics in the POC-PCR-group within the first 2 days is an interesting observation. It is based on analysis of a small subset of culture-positive samples; therefore, it is unknown if the result completely or in part can be extrapolated to the rest of the study population. Nevertheless, it highlights the question if POC-PCR improves patient outcome. We did not find any difference in mortality or transferal to ICU—but the number of events was very low. There was no difference in the number of readmissions but we did find a nonsignificant reduction in LOS from 4.3 to 3.6 days (At day 5, more patients in the SCO group were treated with no or narrow-spectrum antibiotics and there was no difference in the use of targeted antibiotics. This observation may be explained by routine microbiological results being available between day 2 and 5—allowing adjustment of treatment. Even though, we detected statistically significant differences they might be without clinical significance as they were quite small and day 5 is at the end of our recommended treatment duration. The strength of our study is the pragmatic multicentre, RCT design. The randomised design ensured that severity of illness, CAP diagnosis, and other patient characteristics were distributed equally between intervention and control group, and therefore causal inference is likely as the assumption of positivity is fulfilled. The POC-PCR analysis was integrated in the usual workflow in our ED suggesting that the test is technically feasible and easy to implement in other EDs. Project assistants were trained in collecting LRT-specimens and in using the POC-PCR platform and the primary investigator monitored the project closely to ensure a high level of internal validity. Almost 80% of the collected samples were tracheal secretions and this may have increased the reliability of the microbiological results by reducing upper airway contamination [There are also a number of limitations. Only few patients with CURB-65 scores ≥3 (14.4%) were included in the study. The inability to consent is likely linked to severe disease and acute cognitive impairment. In addition, restriction to weekdays and daytime may have reduced the number of severe cases as admission on weekends and at night are known to be associated with increased mortality and risk of referral to ICU [Both culture and POC-PCR may detect commensals, which was stated clearly in the provided action card. It is therefore possible that the clinicians in some situations chose to ignore the result—e.g., based on severity of illness, response to current treatment, fear of prescribing inadequate treatment, likelihood of commensal pathogen, and expected virulence of the pathogen [A possible interpretation of the overall results is that the current restrictive prescribing strategy in Denmark may be unable to provide targeted and adequate treatment for some patients. This may be overcome by introducing broad-spectrum empirical regimes—but that would fuel a further rise in resistance, may introduce side effects, and go against our general antimicrobial stewardship interventions. However, as indicated in this study, we might get around this problem by introducing fast and sensitive diagnostic methods. Future studies should focus on (i) the impact of POC-PCR on clinical outcome in a larger scale—e.g., LOS, length of treatment, and patient quality of life; (ii) hospitalisation costs; and (iii) the use of adequate and target treatment in a blinded setup where sensitive molecular methods are applied in both intervention and control groups. In conclusion, in this randomised trial introduction of POC-PCR did not increase the proportion of patients prescribed no or narrow-spectrum antibiotics but it might increase early treatment with adequate and targeted antibiotics and may be associated with a reduced LOS. The results apply to a setting with restrictive use of antibiotics and a very low level of antimicrobial resistance and may be quite different in other settings. Fast and accurate diagnostic tools may aid to maintain a restrictive use of antibiotics in the future.