Abstract
Carbapenem-resistant Klebsiella pneumoniae (CRKP) frequently causes hospital-acquired infections and is associated with high morbidity and mortality. CRKP can have multiple resistance mechanisms and only a few can be routinely detected by commercial molecular or phenotypic assays making surveillance for CRKP particularly challenging. In this report, we identified and characterized an unusual non–carbapenemase-producing CRKP carrying a rare plasmid-borne inducible AmpC gene, blaDHA-1. The isolate was recovered from blood culture of a 67-year-old female presenting with sepsis post bladder surgery and ureteral stent removal. The primary isolate displayed an indeterminate susceptibility pattern for ceftriaxone by broth microdilution, but was susceptible by disk diffusion with one colony growing within the zone of inhibition. The ceftriaxone resistant colony was sub-cultured and had a minimum inhibitory concentration (MIC) of 2 ug/ml for imipenem (intermediate) and a zone size of 18 mm for ertapenem (resistant), but remained susceptible to cefepime and meropenem. Further phenotypic characterization of this sub-cultured isolate showed carbapenemase activity. Whole genome sequencing (WGS) revealed the presence of two subpopulations of a K. pneumoniae (MLST sequence type 11) from the primary blood culture isolate: one pan-susceptible to beta-lactams tested and the other resistant to the 3rd generation cephalosporins and ertapenem. WGS analysis identified the resistant K. pneumoniae harboring IncFIB(K) and IncR plasmids and the presence of plasmid-borne beta-lactam resistance genes bla OXA-1 and bla DHA-1, an inducible AmpC gene. Additional resistance genes against quinolones (aac(6′)-Ib-cr, oqxA, oqB), aminoglycoside (aph(3′)-Ia), sulfonamide (sul1), and tetracycline (tet(A)) were also identified. DHA-1 positive K. pneumoniae have been previously identified outside the US, particularly in Asia and Europe, but limited cases have been reported in the United States and may be underrecognized. Our study highlights the importance of using both extended phenotypic testing and WGS to identify emerging resistance mechanisms in clinical Enterobacterales isolates with unusual antimicrobial resistance patterns.
Highlights
Klebsiella pneumoniae is a gram-negative rod and a member of the Enterobacterales family
We describe the detection of AmpC expression in a subpopulation of K. pneumoniae recovered from a blood culture using phenotypic antimicrobial susceptibility testing, carbapenemase assays and Whole genome sequencing (WGS)
The AmpC encoding gene, blaDHA-1, was detected in Isolate 1B but not in 1A, which is consistent with phenotypic susceptibility results and carbapnemase test results
Summary
Klebsiella pneumoniae is a gram-negative rod and a member of the Enterobacterales family. These organisms are known to cause significant nosocomial infections with a wide range of clinical presentations including pneumonia, bacteremia, and urinary tract infections. One under-recognized resistance mechanism of particular concern is plasmid encoded AmpC-type beta-lactamase. Inducible AmpC beta-lactamase activity is typically chromosomally encoded and is characteristic in a group of Enterobacterales species, commonly referred to as the “SPICE” group, which include Serratia marcescens, Pseudomonas aeruginosa, indole-positive Proteus, Citrobacter freundii, and Enterobacter cloacae. One exception is plasmid encoded blaDHA-1 which is usually adjacent to ampR, the transcriptional regulator gene for activation or repression of AmpC (Barnaud et al, 1998; Verdet et al, 2006; Compain et al, 2014; Luan et al, 2015), making it similar to inducible chromosomal AmpC enzymes
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