Assessment of Colistin Heteroresistance among Multidrug-Resistant <i>Klebsiella pneumoniae</i> Isolated from Intensive Care Patients in Europe

• Main Authors: Anouk J. M. M. Braspenning (Author), Sahaya Glingston Rajakani (Author), Adwoa Sey (Author), Mariem El Bounja (Author), Christine Lammens (Author), Youri Glupczynski (Author), Surbhi Malhotra-Kumar (Author)
• Format: Book
• Published: MDPI AG, 2024-03-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

Heteroresistance (HR) to colistin is especially concerning in settings where multi-drug-resistant (MDR) <i>K. pneumoniae</i> are prevalent and empiric use of colistin might lead to treatment failures. This study aimed to assess the frequency of occurrence of colistin HR (CHR) among (MDR) <i>K. pneumoniae</i> (<i>n</i> = 676) isolated from patients hospitalized in 13 intensive care units (ICUs) in six European countries in a clinical trial assessing the impact of decolonization strategies. All isolates were whole-genome-sequenced and studied for in vitro colistin susceptibility. The majority were colistin-susceptible (CS) (<i>n</i> = 597, MIC ≤ 2 µg/mL), and 79 were fully colistin-resistant (CR) (MIC > 2 µg/mL). A total of 288 CS isolates were randomly selected for population analysis profiling (PAP) to assess CHR prevalence. CHR was detected in 108/288 CS <i>K. pneumoniae</i>. No significant association was found between the occurrence of CHR and country, MIC-value, K-antigen type, and O-antigen type. Overall, 92% (617/671) of the <i>K. pneumoniae</i> were MDR with high prevalence among CS (91%, 539/592) and CR (98.7%, 78/79) isolates. In contrast, the proportion of carbapenemase-producing <i>K. pneumoniae</i> (CP-Kpn) was higher among CR (72.2%, 57/79) than CS isolates (29.3%, 174/594). The proportions of MDR and CP-Kpn were similar among CHR (MDR: 85%, 91/107; CP-Kpn: 29.9%, 32/107) and selected CS isolates (MDR: 84.7%, 244/288; CP-Kpn: 28.1%, 80/285). WGS analysis of PAP isolates showed diverse insertion elements in <i>mgrB</i> or even among technical replicates underscoring the stochasticity of the CHR phenotype. CHR isolates showed high sequence type (ST) diversity (Simpson's diversity index, SDI: 0.97, in 52 of the 85 STs tested). CR (SDI: 0.85) isolates were highly associated with specific STs (ST101, ST147, ST258/ST512, <i>p</i> ≤ 0.003). The widespread nature of CHR among MDR <i>K. pneumoniae</i> in our study urge the development of rapid HR detection methods to inform on the need for combination regimens.

Item Description

10.3390/antibiotics13030281
2079-6382