A Nationwide Screen of Carbapenem-Resistant Klebsiella pneumoniae Reveals an Isolate with Enhanced Virulence and Clinically Undetected Colistin Heteroresistance

Abstract

The convergence of hypervirulence and multidrug resistance in Klebsiella pneumoniae is a significant concern. Here, we report the first screen for hypermucoviscosity, a trait associated with increased virulence, using a U.S. surveillance collection of carbapenem-resistant (CR) K. pneumoniae isolates. We identified one hypermucoviscous isolate, which carried a gene encoding the KPC-3 carbapenemase, among numerous resistance genes. The strain further exhibited colistin heteroresistance undetected by diagnostics. This convergence of diverse resistance mechanisms and increased virulence underscores the need for enhanced K. pneumoniae surveillance.

Keywords: KPC; Klebsiella; colistin; heteroresistance; hypermucoviscous.

FIG 1

CDC98 displays increased virulence compared to that of nonhypermucoviscous K. pneumoniae isolates. Mice were infected intraperitoneally with CDC98 or the indicated nonhypermucoviscous K. pneumoniae isolates. Results shown are the combination of two independent experiments (n = 10 total). Comparison of survival curves was performed with the Mantel-Cox test (P = 0.0004).

FIG 2

CDC98 displays heteroresistance to the last-line antibiotic colistin. (A) Population analysis profile (PAP) of CDC98 reveals a subpopulation of colistin-resistant cells. The dotted line represents the CLSI epidemiological cutoff value (ECV) for determining K. pneumoniae susceptibility or resistance to colistin (16). (B) CDC98 was designated by Etest as susceptible to colistin.