Methods

From March 1, 2020, to February 28, 2022, we performed a quasi-experimental study to evaluate the role of PCT-CPIS score in reducing inappropriate antibiotic use among COVID-19 patients in 2 hospitals. The first hospital (Thammasat University Hospital or TUH) is a 600-bed tertiary-care university hospital consisting of a cohort unit where mildly-to-moderately ill COVID-19 patients receive care, with 4 ICUs where severely-to-critically ill COVID-19 patients receive care. At the same time, 2 other ICUs were part of a separate pilot study and were excluded. ^{Reference Sathitakorn, Jantarathaneewat and Weber5} Care in these units was directed by ICU physicians and infectious disease (ID) physicians. The second hospital (Lerdsin hospital) is a 500-bed government hospital consisting of a cohort unit where mildly-to-moderately ill COVID-19 patients receive care and 1 ICU where severely-to-critically ill COVID-19 patients receive care. Care in these units is directed by ID physicians. The study periods consisted of a 1-year preimplementation period of PCT-CPIS protocol (period 1: March 1, 2020, to February 28, 2021) and a 1-year postimplementation period of PCT-CPIS protocol (period 2: March 1, 2021, to February 28, 2022). During period 1, no antibiotic protocols for COVID-19 patients were available at either hospital. Before period 2, the PCT-CPIS protocol was discussed and approved by physicians in 2 hospitals. During period 2, upon admission, the researchers calculated the CPIS score (COVID-19 version) ^{Reference Schurink6} and ordered admission PCT for all COVID-19 patients. For those with a CPIS score <6 and a PCT <0.5 μg/L, no antibiotics were initiated. On hospitalization day 3, PCT-CPIS score were reassessed. If the patient’s CPIS was <6 and the PCT was <0.5 μg/L or the PCT dropped by ≥80% from admission level, antibiotics were discontinued (Supplementary Fig. 1). In these ICUs, routine evaluations of bacterial coinfections at all sites were performed at admission and during hospitalization if the patients were not responding to therapy. These evaluations included sputum Gram stain and culture, urine culture, blood culture, and chest radiograph. The protocol was monitored by researchers to ensure strict compliance by treating physicians.

Fig. 1.

Inappropriate antibiotic use, incidence of multidrug-resistant organisms (MDROs) and invasive fungal infections (IFIs), and incidence of MDR Acinetobacter baumannii in 2 medical centers.

The primary outcome was the role of PCT-CPIS in reducing inappropriate antibiotic use among COVID-19 patients. The secondary outcomes were antibiotic duration, length of hospital stay (LOS), 30-day mortality, and MDRO IFIs incidence. Antibiotic appropriateness was defined according to Kunin et al ^{Reference Kunin, Tupasi and Craig7} and was justified by the hospital’s ASP team. Criteria for PCT and COVID-19 pneumonia severity were defined as previously described. ^{Reference Lee, Kwa and Apisarnthanarak8,Reference Wei9} The CPIS score for pneumonia was defined according to Singh et al ^{Reference Singh, Rogers, Atwood, Wagener and Yu10} and was modified for use in COVID-19 pneumonia patients. ^{Reference Schurink6} The inclusion criteria were adults (aged ≥18 years) with COVID-19 infection. Patients who received antibiotics<24 hours or for other indications (eg, surgical prophylaxis) were excluded. This study was approved by the TUH Institutional Review Board.

All analyses were performed using SPSS version 26 software (IBM, Armonk, NY). We used χ² tests to compare categorical variables. Mann–Whitney U tests were used for continuous data. All P values were 2-tailed, and P < .05 was considered statistically significant. A trend analysis was performed to evaluate the overall pattern of changes on outcomes of interest over time using segmented regression analysis of interrupted time series (ITS).