Our latest research was just published in the prestigious Journal of Antimicrobial Chemotherapy (British Society for Antimicrobial Chemotherapy), February 15, 2023.

A carbapenem-focused antimicrobial stewardship programme implemented during the COVID-19 pandemic in a setting of high endemicity for multidrug-resistant Gram-negative bacteria

by

Nikolaos Spernovasilis, Evangelos I Kritsotakis, Anna Mathioudaki, Alexandra Vouidaski, Christos Spanias, Maria Petrodaskalaki, Petros Ioannou, Georgios Chamilos, Diamantis P Kofteridis

Access the full paper via:

• Oxford University Press
• PubMed 

Abstract

Background: Greece is among the countries characterized by high rates of antimicrobial resistance and high consumption of antibiotics, including carbapenems.

Objectives: To measure the impact of a carbapenem-focused antimicrobial stewardship programme (ASP) on the antibiotic consumption and patient outcomes in a Greek tertiary hospital during the COVID-19 pandemic.

Methods: A quasi-experimental, before-after study, comparing a 12 month pre-intervention period with a 12 month intervention period in which a carbapenem-focused ASP was implemented.

Results: A total of 1268 patients were enrolled. The proportion of admitted patients who received carbapenems decreased from 4.1% (842 of 20 629) to 2.3% (426 of 18 245) (-1.8%; P < 0.001). A decrease of -4.9 DDD/100 patient-days (PD) (95% CI -7.3 to -2.6; P = 0.007) in carbapenem use and an increase in the use of piperacillin/tazobactam [+2.1 DDD/100 PD (95% CI 1.0-3.3; P = 0.010)] were observed. Thirty-day mortality following initiation of carbapenem treatment and all-cause in-hospital mortality remained unaltered after ASP implementation. In contrast, length of hospital stay increased (median 17.0 versus 19.0 days; P < 0.001), while the risk of infection-related readmission within 30 days of hospital discharge decreased (24.6% versus 16.8%; P = 0.007). In the post-implementation period, acceptance of the ASP intervention was associated with lower daily hazard of in-hospital death [cause-specific HR (csHR) 0.49; 95% CI 0.30-0.80], lower odds of 30 day mortality (OR 0.36; 95% CI 0.18-0.70) and higher rate of treatment success (csHR 2.45; 95% CI 1.59-3.77).

Conclusions: Implementing and maintaining a carbapenem-focused ASP is feasible, effective and safe in settings with high rates of antimicrobial resistance, even during the COVID-19 pandemic.

Statistical methods

The effect of the antimicrobial stewardship programme (ASP) implementation on hospital antibiotic use was assessed using interrupted time series analyses. A segmented Poisson regression model was employed to examine the extent to which the ASP was associated with an immediate level change and/or a gradual trend change of the monthly numbers of carbapenem-treated patients. In this model, the series of monthly counts of carbapenem-treated patients formed the dependent variable. Independent variables were the time elapsed since the start of the study, the ASP implementation indicator (post- versus pre-ASP), and the time after the intervention. The monthly series of hospital admissions (log transformed) was used as an offset variable to convert the outcome into a rate that accounts for variation in the hospital population size over time. Two pairs of sine-cosine Fourier functions of time were included to capture seasonality. The model coefficients were estimated using the maximum likelihood method. Residual autocorrelation was ruled out by examining autocorrelation graphs. Sensitivity analyses were conducted by using the monthly numbers of hospitalised patients and patient-days as alternative denominators for the treatment rate, and by inflating the standard errors by the scaled Pearson chi-square statistics to adjust for the possibility of overdispersion

In addition, we examined temporal trends in the consumption of carbapenems and other selected antibiotics active against multidrug-resistant Gram-negative bacteria using quarterly hospital data. A level-change linear regression model for interrupted time series was used for this purpose. Stratification per quarter was employed to adjust for seasonality. The model was estimated using the ordinary least squares method and Newey-West standard errors were used to account for autocorrelation.

The impact on patient outcomes was assessed on an intention-to-treat (ITT) principle by comparing all carbapenem-treated patients between the pre-implementation and the ASP intervention periods. Pearson's chi-squared test was used to assess between-group differences in overall proportions of in-hospital mortality, total mortality within 30 days of initiation of carbapenem treatment, and infection-related readmission within 30 days of hospital discharge. The Wilcoxon rank-sum test was used to assess between-group differences in length of hospital stay. Multivariable Cox regression was employed to obtain cause-specific hazard ratios (csHR) for in-hospital death and discharge alive, adjusting for differences in baseline covariates. The time origin was set to hospital admission. Discharge alive from the hospital was treated as a competing event to in-hospital death. In this analysis, a low csHR for discharge alive reflects a low daily rate of discharge resulting in prolonged hospital stay. Multivariable logistic regression was employed to estimate odds ratios (OR) for total mortality within 30 days of initiation of carbapenem treatment and OR for infection-related readmission within 30 days of hospital discharge, correcting for differences in baseline covariates. All models adjusted for patient sex, age, ward of hospitalisation, and history of previous hospitalisation.

A series of sensitivity analyses were performed to assess the likely clinical impact of the ASP intervention under different conditions. On a modified ITT analysis, we compared the pre-implementation cohort to the post-implementation cohort, excluding patients for whom the intervention was not accepted. On per-protocol analysis, we compared patients who did not receive the intervention in either the pre- or the post-implementation period with those who received the intervention. Finally, restricting the analysis within the post-implementation period, we compared patients for whom the intervention was accepted with patients for whom the intervention was not. In the latter analysis, we additionally compared the clinical outcome at the end of therapy.

None of the study variables had missing data. Statistical significance was considered at the usual P < 0.05 threshold. Data processing and statistical modelling were performed using Stata version 17 (Stata Corp., College Station, TX, USA).