Fecal microbiota dynamics during Klebsiella pneumoniae carbapenemase (KPC) acquisition in Long-Term Acute Care Hospital (LTACH) patients

Background: KPC-producing bacteria pose a serious healthcare problem. Colonization with KPC typically precedes infection; identification of novel risk factors for colonization acquisition may reveal new targets for infection prevention. This study prospectively compared the fecal microbiota in LTACH patients who acquired KPC to identify potential microbial signatures associated with acquisition.

 

Methods: Weekly rectal swab samples were collected from patients admitted to one LTACH from May-October 2015; medical records were reviewed. Sampling was conducted throughout the patients’ stays at weekly intervals. Samples underwent qPCR for bla_KPC to determine KPC status. To compare the microbiota community in patients over time, total DNA from each sample was isolated, and the 16S rRNA V4 region was PCR-amplified and sequenced. Sequences were processed using mothur. Alpha and beta diversity measures were calculated to determine microbiota differences between patients and within a patient over time.

 

Results: 32 patients acquired KPC. 11 (31%) were women, with a median age of 63 yrs. Median length of stay before acquisition was 21 days; antibiotics were received for a median 74% of days. For KPC-converters, an average of 4.8 samples were collected/patient; 46% were positive for KPC. Samples clustered into 5 phylotypes using the partitioning around medoids (PAM) clustering (average silhouette score = 0.20). We saw no significant difference in alpha diversity (inverse Simpson index) between KPC positive or negative samples. However, a decrease in microbiota diversity occur­red immediately prior to and at initial KPC acquisition (Kruskal-Wallis test, p = 0.053) (Figure). Comparison of intra-individual variation within patients over time also revealed changes in community similarity surrounding KPC acquisition.

 

Conclusion: While diversity of the microbiota did not differ significantly between KPC negative and positive samples, the group-level reduction in diversity observed prior to and at the time of KPC acquisition suggests that changes may occur in the fecal bacterial community in association with acquisition of KPC. The nature of these changes and whether they can be modified to reduce the risk of KPC acquisition require further investigation.