# Flying under the radar: vancomycin heteroresistance in Staphylococcus epidermidis peritonitis is associated with treatment failure

## TL;DR

A patient with peritoneal dialysis peritonitis caused by Staphylococcus epidermidis failed vancomycin treatment due to undetected heteroresistance, highlighting diagnostic limitations.

## Contribution

Demonstrates vancomycin heteroresistance in S. epidermidis peritonitis undetected by standard AST and whole-genome sequencing.

## Key findings

- Vancomycin heteroresistance in S. epidermidis was undetected by VITEK 2 and broth-microdilution AST.
- Population analysis profiling confirmed heteroresistance despite conventional susceptibility results.
- Whole-genome sequencing failed to identify genetic mechanisms behind the heteroresistance.

## Abstract

Antimicrobial resistance (AMR) is a global One Health problem and a growing threat to human and animal health. Antimicrobial susceptibility tests (AST) such as the broth-microdilution method (BMD) guide appropriate antimicrobial therapy but may fail to detect various forms of AMR, such as heteroresistance. We report vancomycin treatment failure in a Staphylococcus epidermidis peritoneal dialysis (PD) associated peritonitis case with vancomycin heteroresistance undetected by conventional AST and whole-genome sequencing.

A patient with cloudy PD effluent presented to his local dialysis center. Samples were sent for testing, and empirical treatment with vancomycin and gentamicin was initiated. An S. epidermidis isolate (C099) was cultured, and treatment was changed to vancomycin monotherapy, with the isolate recorded as susceptible using the VITEK 2. Despite treatment, effluent remained culture positive, and two additional S. epidermidis isolates were cultured (C100 and C101). These isolates were also recorded as susceptible to vancomycin using the VITEK 2. Seventeen days post-presentation, the PD catheter was removed due to persistent infection, and the patient was transferred to hemodialysis.

Conventional AST (VITEK 2 and BMD) misclassified the isolates as vancomycin susceptible, while population analysis profiling area under the curve confirmed heteroresistance. Whole-genome sequencing did not identify genetic mechanisms for the heteroresistance, with no mutations detected in known resistance-associated genes. This study highlights the limitations of conventional AST and genomic methods for AMR detection, emphasizing the need for further research into cryptic forms of heteroresistance to enhance diagnostic accuracy and improve patient outcomes.