AUTHOR=Smit Pieter W. , Stoesser Nicole , Pol Sreymom , van Kleef Esther , Oonsivilai Mathupanee , Tan Pisey , Neou Leakhena , Turner Claudia , Turner Paul , Cooper Ben S. 

TITLE=Transmission Dynamics of Hyper-Endemic Multi-Drug Resistant Klebsiella pneumoniae in a Southeast Asian Neonatal Unit: A Longitudinal Study With Whole Genome Sequencing

JOURNAL=Frontiers in Microbiology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2018.01197

DOI=10.3389/fmicb.2018.01197

ISSN=1664-302X

ABSTRACT=<p><bold>Background:</bold><italic>Klebsiella pneumoniae</italic> is an important and increasing cause of life-threatening disease in hospitalized neonates. Third generation cephalosporin resistance (3GC-R) is frequently a marker of multi-drug resistance, and can complicate management of infections. 3GC-R <italic>K. pneumoniae</italic> is hyper-endemic in many developing country settings, but its epidemiology is poorly understood and prospective studies of endemic transmission are lacking. We aimed to determine the transmission dynamics of 3GC-R <italic>K. pneumoniae</italic> in a newly opened neonatal unit (NU) in Cambodia and to address the following questions: what is the diversity of 3GC-R <italic>K. pneumoniae</italic> both within- and between-host; to what extent is high carriage prevalence driven by ward-based transmission; and to what extent can environmental contamination explain patterns of patient acquisition.</p><p><bold>Methods:</bold> We performed a prospective longitudinal study between September and November 2013. Rectal swabs from consented patients were collected upon NU admission and every 3 days thereafter. Morphologically different colonies from swabs growing cefpodoxime-resistant <italic>K. pneumoniae</italic> were selected for whole-genome sequencing (WGS).</p><p><bold>Results:</bold> One hundred and fifty-eight samples from 37 patients and 7 environmental sites were collected. 32/37 (86%) patients screened positive for 3GC-R <italic>K. pneumoniae</italic> and 93 colonies from 119 swabs were successfully sequenced. Isolates were resistant to a median of six (range 3–9) antimicrobials. WGS revealed high diversity; pairwise distances between isolates from the same patient were either 0–1 SNV or &gt;1,000 SNVs; 19/32 colonized patients harbored <italic>K. pneumoniae</italic> colonies differing by &gt;1000 SNVs. Diverse lineages accounted for 18 probable importations to the NU and nine probable transmission clusters involving 19/37 (51%) of screened patients. Median cluster size was five patients (range 3–9). Seven out of 46 environmental swabs (15%) were positive for 3GC-R <italic>K. pneumoniae.</italic> Environmental sources were plausible sources for acquisitions in 2/9 transmission clusters, though in both cases other patients were also plausible sources.</p><p><bold>Conclusion:</bold> The epidemiology of 3GC-R <italic>K. pneumoniae</italic> was characterized by multiple introductions, high within- and between host diversity and a dense network of cross-infection, with half of screened neonates part of a transmission cluster. We found no evidence to suggest that environmental contamination was playing a dominant role in transmission.</p>