Procalcitonin-guided antibiotic prescription in patients with COVID-19: a multicentre observational cohort study

Background Despite the low rate of bacterial co-infection, antibiotics are very commonly prescribed in hospitalised COVID-19 patients. Research question Does the use of a PCT-guided antibiotic protocol safely reduce the use of antibiotics in patients with a COVID-19 infection? Study design and methods In this multicentre cohort, 3 groups of COVID-19 patients were compared in terms of antibiotic consumption, namely one group treated based on a PCT-algorithm in one hospital (n=216) and 2 control groups, consisted of patients from the same hospital (n=57) and of patients from 3 similar hospitals (n=486) without PCT measurements during the same period. The primary endpoint was antibiotic prescription in the first week of admission. Results Antibiotic prescription during the first 7 days was 26.8% in the PCT-group, 43.9% in the non-PCT group in the same hospital and 44.7% in the non-PCT group in other hospitals. Patients in the PCT-group had lower odds of receiving antibiotics in the first 7 days of admission (OR 0.33;0.16 - 0.66 compared to the same hospital and OR 0.42;95% CI 0.28 – 0.62 compared to the other hospitals). The proportion of patients receiving antibiotic prescription during the total admission was respectively 35.2%, 43.9% and 54.5%. The PCT-group had lower odds of receiving antibiotics during the total admission only when compared to the other hospitals (OR 0.23;95%CI 0.08 - 0.63). There were no significant differences in other secondary endpoints, except for re-admission in the PCT-group versus the other hospitals group. Interpretation : PCT-guided antibiotic prescription reduces antibiotic prescription rates in hospitalised patients with COVID-19, without major safety concerns.

Bacillus Calmette-Guérin vaccine to reduce healthcare worker absenteeism in COVID-19 pandemic, a randomized controlled trial.

OBJECTIVES: The COVID-19 pandemic increases healthcare worker (HCW) absenteeism. The bacillus Calmette-Guérin (BCG) vaccine may provide non-specific protection against respiratory infections through enhancement of trained immunity. We investigated the impact of BCG vaccination on HCW absenteeism during the COVID-19 pandemic. METHODS: HCWs exposed to COVID-19 patients in nine Dutch hospitals were randomized to BCG vaccine or placebo in a 1:1 ratio, and followed for one year using a mobile phone application. The primary endpoint was the self-reported number of days of unplanned absenteeism for any reason. Secondary endpoints included documented COVID-19, acute respiratory symptoms or fever. This was an investigator-funded study, registered at ClinicalTrials.gov (NCT03987919). RESULTS: In March/April 2020, 1511 HCWs were enrolled. The median duration of follow-up was 357 person-days (interquartile range [IQR], 351 to 361). Unplanned absenteeism for any reason was observed in 2.8% of planned working days in the BCG group and 2.7% in the placebo group (adjusted relative risk 0.94; 95% credible interval, 0.78-1.15). Cumulative incidences of documented COVID-19 were 14.2% in the BCG and 15.2% in the placebo group (adjusted hazard ratio (aHR) 0.94; 95% confidence interval (CI), 0.72-1.24). First episodes of self-reported acute respiratory symptoms or fever occurred in 490 (66.2%) and 443 (60.2%) participants, respectively (aHR: 1.13; 95% CI, 0.99-1.28). Thirty-one serious adverse events were reported (13 after BCG, 18 after placebo), none considered related to study medication. CONCLUSIONS: During the COVID-19 pandemic, BCG-vaccination of HCW exposed to COVID-19 patients did not reduce unplanned absenteeism nor documented COVID-19.

Recommendations for antibacterial therapy in adults with COVID-19 - an evidence based guideline.

SCOPE: The Dutch Working Party on Antibiotic Policy constituted a multidisciplinary expert committee to provide evidence-based recommendation for the use of antibacterial therapy in hospitalized adults with a respiratory infection and suspected or proven 2019 Coronavirus disease (COVID-19). METHODS: We performed a literature search to answer four key questions. The committee graded the evidence and developed recommendations by using Grading of Recommendations Assessment, Development, and Evaluation methodology. QUESTIONS ADDRESSED BY THE GUIDELINE AND RECOMMENDATIONS: We assessed evidence on the risk of bacterial infections in hospitalized COVID-19 patients, the associated bacterial pathogens, how to diagnose bacterial infections and how to treat bacterial infections. Bacterial co-infection upon admission was reported in 3.5% of COVID-19 patients, while bacterial secondary infections during hospitalization occurred up to 15%. No or very low quality evidence was found to answer the other key clinical questions. Although the evidence base on bacterial infections in COVID-19 is currently limited, available evidence supports restrictive antibiotic use from an antibiotic stewardship perspective, especially upon admission. To support restrictive antibiotic use, maximum efforts should be undertaken to obtain sputum and blood culture samples as well as pneumococcal urinary antigen testing. We suggest to stop antibiotics in patients who started antibiotic treatment upon admission when representative cultures as well as urinary antigen tests show no signs of involvement of bacterial pathogens after 48 hours. For patients with secondary bacterial respiratory infection we recommend to follow other guideline recommendations on antibacterial treatment for patients with hospital-acquired and ventilator-associated pneumonia. An antibiotic treatment duration of five days in patients with COVID-19 and suspected bacterial respiratory infection is recommended upon improvement of signs, symptoms and inflammatory markers. Larger, prospective studies about the epidemiology of bacterial infections in COVID-19 are urgently needed to confirm our conclusions and ultimately prevent unnecessary antibiotic use during the COVID-19 pandemic.