Cross-transmission is not the source of newMycobacterium abscessusinfections in a multi-centre cohort of cystic fibrosis patients

Abstract

BackgroundMycobacterium abscessusis an extensively drug resistant pathogen that causes pulmonary disease particularly in cystic fibrosis (CF) patients. Identifying direct patient-to-patient transmission ofM. abscessusis critically important in directing infection control policy for the management of risk in CF patients. A variety of clinical labs have used molecular epidemiology to investigate transmission. However there is still conflicting evidence as to howM. abscessusis acquired and whether cross-transmission occurs. Recently labs have applied whole-genome sequencing (WGS) to investigate this further and in this study we investigate whether WGS can reliably identify cross-transmission inM. abscessus.MethodsWe retrospectively sequenced the whole genomes of 145M. abscessusisolates from 62 patients seen at four hospitals in two countries over 16 years.ResultsWe have shown that a comparison of a fixed number of core single nucleotide variants (SNVs) alone cannot be used to infer cross-transmission inM. abscessusbut does provide enough information to replace multiple existing molecular assays. We detected one episode of possible direct patient-to-patient transmission in a sibling pair. We found that patients acquired uniqueM. abscessusstrains even after spending considerable time on the same wards with otherM. abscessuspositive patients.ConclusionsThis novel analysis has demonstrated that the majority of patients in this study have not acquiredM. abscessusthrough direct patient-patient transmission or a common reservoir. Tracking transmission using WGS will only realise its full potential with proper environmental screening as well as patient sampling.Key pointsWhole genome sequencing should replace current molecular typing used routinely in clinical microbiology laboratories.Patient-to-patient spread ofM. abscessusis not common.Environmental screening may provide a better understanding acquisition ofM. abscessusinfections.

Stenotrophomonas maltophilianatural history and evolution in the airways of adults with cystic fibrosis

“…Our results are in agreement with the previous finding that detection of multiple S. maltophilia strains over time is common (11)(12)(13)(14) and extend previous studies by demonstrating that this pattern may persist for several decades. This pattern of rapid strain acquisition is also consistent with a hypothesis of independent environmental acquisition as the source of new infections in pwCF in CF cohorts with adequate infection control protocols, as has been suggested for other CF pathogens (26,29,32). This is further supported by a lack of epidemiological evidence for infection transmission, and the clonal nature of infecting strains.…”

“…This latter point is particularly relevant, as many studies have identified a significant proportion of patients with shared strains (as defined by molecular methods). While shared strains as determined through molecular methods may indicate the potential for infection transmission (25,26), it is not sufficient to identify a transmission event (27)(28)(29)(30). This is key, as independent acquisition of the same strain without a CF intermediary is well known to occur with other CF pathogens (26,28,29), confounding our ability to understand infection transmission.…”

“…While shared strains as determined through molecular methods may indicate the potential for infection transmission (25,26), it is not sufficient to identify a transmission event (27)(28)(29)(30). This is key, as independent acquisition of the same strain without a CF intermediary is well known to occur with other CF pathogens (26,28,29), confounding our ability to understand infection transmission. To date, no studies of S. maltophilia in CF have investigated its potential to spread between patients.…”

Stenotrophomonas maltophilia natural history and evolution in the airways of adults with cystic fibrosis

“…Our results are in agreement with the previous finding that detection of multiple S. maltophilia strains over time is common (Vidigal et al, 2014;Pompilio et al, 2016;Chung et al, 2017;Esposito et al, 2017) and extend previous studies by demonstrating that this pattern may persist for several decades. This pattern of rapid strain acquisition is also consistent with a hypothesis of independent environmental acquisition as the source of new infections in pwCF in CF cohorts with adequate infection control protocols, as has been suggested for other CF pathogens (Yan et al, 2019;Doyle et al, 2020;Stapleton et al, 2020). This is further supported by a lack of epidemiological evidence for infection transmission, and the clonal nature of intra-pwCF strains.…”

“…This latter point is particularly relevant, as many studies have identified a significant proportion of patients with shared strains (as defined by molecular methods). While shared strains as determined through molecular methods may indicate the potential for infection transmission (Stapleton et al, 2020;Gabrielaite et al, 2021), it is not sufficient to identify a transmission event (Parkins et al, 2018;Doyle et al, 2020;Izydorczyk et al, 2020Izydorczyk et al, , 2022. This is key, as independent acquisition of the same strain without a CF intermediary is well known to occur with other CF pathogens (Doyle et al, 2020;Izydorczyk et al, 2020;Stapleton et al, 2020), confounding our ability to understand infection transmission.…”