Outbreak of colistin-resistant, carbapenem-resistant Klebsiella pneumoniae in metropolitan Detroit, Michigan

Abstract

Carbapenem-resistant Klebsiella pneumoniae has spread worldwide and throughout the United States. Colistin is used extensively to treat infections with this organism. We describe a cluster of colistin-resistant, carbapenem-resistant K. pneumoniae infection cases involving three institutions in Detroit, MI. A cluster of five cases of colistin-resistant, carbapenem-resistant K. pneumoniae was identified at Detroit Medical Center (DMC) from 27 July to 22 August 2009. Epidemiologic data were collected, and transmission opportunities were analyzed. Isolates were genotyped by using pulsed-field gel electrophoresis and repetitive extragenic palindromic PCR. Data regarding the use of colistin were obtained from pharmacy records. The index case of colistin-resistant, carbapenem-resistant K. pneumoniae was followed 20 days later by four additional cases occurring in a 6-day interval. All of the patients, at some point, had stayed at one particular institution. The mean number of opportunities for transmission between patients was 2.3 ± 0.5, and each patient had at least one opportunity for transmission with one of the other patients. Compared to 60 colistin-susceptible, carbapenem-resistant K. pneumoniae controls isolated in the previous year at DMC, case patients were significantly older (P = 0.05) and the carbapenem-resistant K. pneumoniae organisms isolated from them displayed much higher MICs to imipenem (P < 0.001). Colistin use was not enhanced in the months preceding the outbreak. Genotyping revealed two closely related clones. This report of a colistin-resistant, carbapenem-resistant K. pneumoniae outbreak is strongly linked to patient-to-patient transmission. Controlling the spread and novel emergence of bacteria with this phenotype is of paramount importance.

FIG. 1.

Time line and transmission opportunities among patients during the outbreak. Each row represents a patient, and each column represents a week. The colors represent the different units/wards as presented in the legend at the bottom. A transmission opportunity was deemed to have occurred if two patients were in the same ward during the same time period. For example, patients 1 and 2 had a transmission opportunity during week 12 in the Medicine 2 ward. Superscript a: week1, 29 March to 4 April 2009; week 24, 5 to 11 September 2009. Superscript b: date of clinical culture.

FIG. 2.

Dendrograms of carbapenem-resistant Klebsiella species strains, DMC, 2009. (A) Dendrogram showing the relatedness of colistin-resistant KPC-producing K. pneumoniae based on PFGE patterns after digestion with XbaI. Isolates showing 80% similarity are considered related. (B) Dendrogram showing the relatedness of colistin-resistant isolates based on Rep-PCR. Isolates 95% similar are considered related. According to both methods, isolates from patients 1, 3, 4, and 5 are related and represent a single clone. Isolates 29 and 52 are representative colistin-susceptible, KPC-producing K. pneumoniae strains isolated at DMC during the outbreak period.

FIG. 3.

Immunoblot analysis of KPC production by colistin- and carbapenem-resistant K. pneumoniae isolates. Lanes 1 to 5 are the colistin-resistant isolates (MIC, >32 μg/ml for patients 1 through 5). Lanes 6 and 7 are two representative strains of colistin-susceptible, carbapenem-resistant (MIC = 2 μg/ml for both) K. pneumonia (isolates 29 and 52) isolated at DMC during the outbreak period. Lane 8 represents the activity of 200 ng of purified KPC beta-lactamase. Comparison of the blots gives an indication of the relative levels of KPC production.