Long-term endemic situation caused by a linezolid- and meticillin-resistant clone of Staphylococcus epidermidis in a tertiary hospital
Introduction
Coagulase-negative staphylococci (CoNS) are important nosocomial pathogens, mainly in immunocompromised patients or associated with the implantation of medical devices [1]. Staphylococcus epidermidis is the most common CoNS involved in nosocomial infections. According to the ENVIN-HELICS study (http://hws.vhebron.net/envin-helics), S. epidermidis is the most common Gram-positive bacterium isolated in intensive care units (ICUs) in Spain, and the third most common when considering both Gram-positive and Gram-negative bacteria. Nosocomial isolates of S. epidermidis are frequently resistant to the majority of clinically relevant antimicrobials [1]. Consequently, last-resort antimicrobials are often one of the few options to treat infections caused by this species [1]. Linezolid (LZD) and tedizolid are among the last therapeutic options available to combat S. epidermidis infections [2]. These compounds belong to the oxazolidinone family and inhibit protein synthesis at the initial stage, by binding to the peptidyl transferase centre of the bacterial ribosome [2]. LZD has been used extensively in hospitals, especially in ICUs, primarily due to its broad spectrum against Gram-positive bacteria and its pharmacokinetic/pharmacodynamic features [1]. As a result, LZD resistance has emerged in Gram-positive bacteria, mainly S. epidermidis, from ICUs where they can become endemic [3]. The most common mechanism of LZD resistance is a point mutation in the V domain of the 23S rRNA gene, but changes in the ribosomal proteins L3, L4 and L22 can also be involved [4]. Furthermore, the cfr, optrA and poxtA genes, which can be transferred between Gram-positive bacteria, have been associated with resistance to different antimicrobial agents, including oxazolidinones [3,5].
Although several studies have investigated LZD-resistant S. epidermidis (LRSE), they were mainly related to outbreaks and/or hospital wards with high use of LZD, and only a few endemic situations have been reported [1,6,7]. The present study reports a long-term endemic situation caused by a clone of LRSE in a Spanish hospital (Hospital Universitario Central de Asturias, Spain), analysing the relationship between the frequency of LRSE and LZD consumption over time.
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Materials and methods
The rate of LRSE (total number of LRSE/total number of S. epidermidis recovered per year x 100) from 2011 to 2017 was determined retrospectively using the Microbiology Laboratory informatics system at the study hospital. Data on LZD utilization for the same period were obtained from the hospital pharmacy and expressed as defined daily dose (DDD) per 100 patient-days of bed occupancy. Statistical analysis between prevalence of LRSE and LZD consumption was performed using Stata/IC 14.2 for Mac
Results
The relationship between the rate of LRSE and LZD consumption, both in the ICU and other hospital wards, over a 7-year period (2011–2017) is represented in Figure 1. During this period, a total of 5435 S. epidermidis were isolated at the study hospital, and 435 of these were LZD resistant (8.0%). In total, 832 S. epidermidis were found in the ICU and 4603 were found in the remaining wards, with 198 (23.80%) and 237 (5.15%) being LZD resistant, respectively. The number and frequency of LRSE
Discussion
Over the 7-year study period (2011–2017), LRSE were detected consistently at the study hospital in numbers ranging from 42 to 94 per year. All isolates tested were closely related by PFGE and belonged to the ST2 clone. Nosocomial S. epidermidis are dominated by strains of clonal complex 5, and ST2 is the most widely disseminated type [1,12]. ST2 isolates are characterized by a high level of genetic plasticity, related to an increased recombination/mutation rate and the efficient acquisition of
Conflict of interest statement
None declared.
Funding source
A short stay of C.R-L at the Hospital Universitari de Bellvitge was supported by a grant from the Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica.
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