What caused the outbreak of ESBL-producingKlebsiella pneumoniaein a neonatal intensive care unit, Germany 2009 to 2012? Reconstructing transmission with epidemiological analysis and whole-genome sequencing

Abstract

ObjectiveWe aimed to retrospectively reconstruct the timing of transmission events and pathways in order to understand why extensive preventive measures and investigations were not sufficient to prevent new cases.MethodsWe extracted available information from patient charts to describe cases and to compare them to the normal population of the ward. We conducted a cohort study to identify risk factors for pathogen acquisition. We sequenced the available isolates to determine the phylogenetic relatedness of Klebsiella pneumoniae isolates on the basis of their genome sequences.ResultsThe investigation comprises 37 cases and the 10 cases with ESBL (extended-spectrum beta-lactamase)-producing K. pneumoniae bloodstream infection. Descriptive epidemiology indicated that a continuous transmission from person to person was most likely. Results from the cohort study showed that ‘frequent manipulation’ (a proxy for increased exposure to medical procedures) was significantly associated with being a case (RR 1.44, 95% CI 1.02 to 2.19). Genome sequences revealed that all 48 bacterial isolates available for sequencing from 31 cases were closely related (maximum genetic distance, 12 single nucleotide polymorphisms). Based on our calculation of evolutionary rate and sequence diversity, we estimate that the outbreak strain was endemic since 2008.ConclusionsEpidemiological and phylogenetic analyses consistently indicated that there were additional, undiscovered cases prior to the onset of microbiological screening and that the spread of the pathogen remained undetected over several years, driven predominantly by person-to-person transmission. Whole-genome sequencing provided valuable information on the onset, course and size of the outbreak, and on possible ways of transmission.

Nursing staff fluctuation and pathogenic burden in the NICU - effective outbreak management and the underestimated relevance of non-resistant strains

“…Thus, this strongly underscores the essential importance of adequate staff-patient ratios as constituted by the national guidelines1618. Noticeably, when compared to most reports on microbial outbreaks on NICUs that usually describe one specifically causative pathogen262728 the here described outbreak involved multiple different organisms. Furthermore, this outbreak was unusually long-lasting covering a period of almost 9 months.…”

The emergence of carbapenem resistant Klebsiella pneumoniae in Malaysia: correlation between microbiological trends with host characteristics and clinical factors

“…During an outbreak investigation of ESBL producing K. pnemoniae in a neonatal intensive care unit in Germany, Haller and co-workers [23] found two isolates from the same patient taken 138 days apart to be affiliated with separate clusters on phylogenetic tree. This could indicate the presence of diverse pathogen populations within individuals which complicates treatment.…”

Pathogen Population Structure Can Explain Hospital Outbreaks

“…The discontinuity of infections in outbreaks are periods of time in which there is a gap between recognized cases. Often, additional infections are later identified as being caused by the same strain 8–12 without any epidemiological link between the infected hosts (such as asymptomatic carriers). Thus discontinuity can sometimes be partially explained by genomic data and surveillance monitoring during and after outbreaks, such as in the identification of previously unknown infections 12 .…”

“…Often, additional infections are later identified as being caused by the same strain 8–12 without any epidemiological link between the infected hosts (such as asymptomatic carriers). Thus discontinuity can sometimes be partially explained by genomic data and surveillance monitoring during and after outbreaks, such as in the identification of previously unknown infections 12 . Additionally, these discontinuous “breaks” can occur for unexpectedly long periods of time, during which hospital epidemiologists may believe that a particular pathogen is no longer present within their facility.…”