Antibiotic use during coronavirus disease 2019 intensive care unit shape multidrug resistance bacteriuria: A Swedish longitudinal prospective study

Philip A Karlsson; Julia Pärssinen; Erik A Danielsson; Nikos Fatsis-Kavalopoulos; Robert Frithiof; Michael Hultström; Miklos Lipcsey; Josef D Järhult; Helen Wang

doi:10.3389/fmed.2023.1087446

Antibiotic use during coronavirus disease 2019 intensive care unit shape multidrug resistance bacteriuria: A Swedish longitudinal prospective study

Front Med (Lausanne). 2023 Feb 7:10:1087446. doi: 10.3389/fmed.2023.1087446. eCollection 2023.

Authors

Affiliations

¹ Department of Medical Biochemistry and Microbiology, Uppsala University, Uppsala, Sweden.
² Department of Surgical Sciences, Anesthesiology and Intensive Care Medicine, Uppsala University, Uppsala, Sweden.
³ Department of Medical Cell Biology, Integrative Physiology, Uppsala University, Uppsala, Sweden.
⁴ Hedenstierna Laboratory, CIRRUS, Department of Surgical Sciences, Anesthesiology and Intensive Care Medicine, Uppsala University, Uppsala, Sweden.
⁵ Department of Medical Sciences, Zoonosis Science Center, Uppsala University, Uppsala, Sweden.

Abstract

Objectives: High frequency of antimicrobial prescription and the nature of prolonged illness in COVID-19 increases risk for complicated bacteriuria and antibiotic resistance. We investigated risk factors for bacteriuria in the ICU and the correlation between antibiotic treatment and persistent bacteria.

Methods: We conducted a prospective longitudinal study with urine from indwelling catheters of 101 ICU patients from Uppsala University Hospital, Sweden. Samples were screened and isolates confirmed with MALDI-TOF and whole genome sequencing. Isolates were analyzed for AMR using broth microdilution. Clinical data were assessed for correlation with bacteriuria.

Results: Length of stay linearly correlated with bacteriuria (R² = 0.99, p ≤ 0.0001). 90% of patients received antibiotics, primarily the beta-lactams (76%) cefotaxime, piperacillin-tazobactam, and meropenem. We found high prevalence of Enterococcus (42%) being associated with increased cefotaxime prescription. Antibiotic-susceptible E. coli were found to cause bacteriuria despite concurrent antibiotic treatment when found in co-culture with Enterococcus.

Conclusion: Longer stays in ICUs increase the risk for bacteriuria in a predictable manner. Likely, high use of cefotaxime drives Enterococcus prevalence, which in turn permit co-colonizing Gram-negative bacteria. Our results suggest biofilms in urinary catheters as a reservoir of pathogenic bacteria with the potential to develop and disseminate AMR.

Keywords: AMR; COVID-19; ICU–intensive care unit; MDR–(multidrug resistance); UTI; antibiotic treatment; catheters.

Grants and funding

This study was funded by the Swedish Society for Medical Research Stora Anslag (HW: S18-0174), the Swedish Research Council (HW: 2018-02376, JJ: c, RF: 2014-02569 and 2014-07606), SciLifeLab/Knut and Alice Wallenberg national COVID-19 research program (MH: KAW 2020.0182 and KAW 2020.0241), the Swedish Heart-Lung Foundation (MH: 20210089, 20190639 and 20190637), and the Swedish Kidney Foundation (RF: F2020-0054).