Combined antibiotic stewardship and infection control measures to contain the spread of linezolid-resistant Staphylococcus epidermidis in an intensive care unit

Abstract

Background The unrestricted use of linezolid has been linked to the emergence of linezolid-resistant Staphylococcus epidermidis (LRSE). We report the effects of combined antibiotic stewardship and infection control measures on the spread of LRSE in an intensive care unit (ICU). Methods Microbiological data were reviewed to identify all LRSE detected in clinical samples at an ICU in southwest Germany. Quantitative data on the use of antibiotics with Gram-positive coverage were obtained in defined daily doses (DDD) per 100 patient-days (PD). In addition to infection control measures, an antibiotic stewardship intervention was started in May 2019, focusing on linezolid restriction and promoting vancomycin, wherever needed. We compared data from the pre-intervention period (May 2018–April 2019) to the post-intervention period (May 2019–April 2020). Whole-genome sequencing (WGS) was performed to determine the genetic relatedness of LRSE isolates. Results In the pre-intervention period, LRSE were isolated from 31 patients (17 in blood cultures). The average consumption of linezolid and daptomycin decreased from 7.5 DDD/100 PD and 12.3 DDD/100 PD per month in the pre-intervention period to 2.5 DDD/100 PD and 5.7 DDD/100 PD per month in the post-intervention period (p = 0.0022 and 0.0205), respectively. Conversely, vancomycin consumption increased from 0.2 DDD/100 PD per month to 4.7 DDD/100 PD per month (p < 0.0001). In the post-intervention period, LRSE were detected in 6 patients (4 in blood cultures) (p = 0.0065). WGS revealed the predominance of one single clone. Conclusions Complementing infection control measures by targeted antibiotic stewardship interventions was beneficial in containing the spread of LRSE in an ICU.

Molecular Characterization of Clinical Linezolid-Resistant Staphylococcus epidermidis in a Tertiary Care Hospital

“…WGS and subsequent extraction of the seven MLST targets identified all 15 LRSE isolates as ST2. This ST is frequently associated with nosocomial infections and blood stream infections [ 8 , 12 , 26 , 28 ]. In-depth analysis revealed that the SCC mec type III was detected in all isolates.…”

“…For all WGS datasets, we utilized the software SeqSphere + (Ridom GmbH, Münster, Germany, version 9.0.0) to compare coding regions in a gene-by-gene approach, i.e., core genome multilocus sequence typing (cgMLST), as described previously [ 25 ]. To analyze genetic relatedness, we used the recently published cgMLST scheme for S. epidermidis [ 26 ]. Clonal relationship of genotypes is here displayed using a minimum spanning tree algorithm calculated by the same software and is rated as closely related if genotypes differ in ≤6 alleles.…”

“…Only samples with ≥95% valid targets were included in our comparison. Afterwards, we used cgMLST to compare 15 isolates identified at the UHM to previously published LRSE samples [ 8 , 12 , 26 , 28 ]. For additional analysis, single nucleotide polymorphisms were extracted from core genome genes present in all isolates.…”

Staphylococcus massiliensis isolated from human blood cultures, Germany, 2017–2020

“…aureus complex [ 4 , 5 ]. Device-related infections are one of the most common manifestations of CoNS infections, causing high morbidity and mortality [ 6 , 7 ]. With the advent of modern tools in routine microbiological diagnostics such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), pathogen detection has experienced a remarkable refinement within the past decade [ 8 , 9 ].…”

“…Coagulase-negative staphylococci (CoNS) are abundant inhabitants of the human skin and the mucosa with limited pathogenicity [1,2], as opposed to Staphylococcus aureus [3] and other members of the S. aureus complex [4,5]. Device-related infections are one of the most common manifestations of CoNS infections, causing high morbidity and mortality [6,7]. With the advent of modern tools in routine microbiological diagnostics such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), pathogen detection has experienced a remarkable refinement within the past decade [8,9].…”