The first culture of colistin-resistant, carbapenem-resistant K. pneumoniae was obtained on 27 July 2009, followed by four additional cases occurring between 16 and 22 August 2009. All isolations were from clinical cultures; none were from surveillance cultures. Table depicts the patients' characteristics and outcomes. In general, patients were elderly, frail individuals with multiple complicated comorbid conditions who had numerous exposures to environments and settings where nosocomial infections can occur. Three of the patients reside permanently in nursing homes (different ones), and two reside in the LTAC facility attached to hospital A. In addition to the antimicrobials displayed in Table , all of the colistin-resistant, carbapenem-resistant K. pneumoniae strains were resistant to meropenem, ceftazidime, amikacin, and ciprofloxacin, while two out of five were susceptible to tigecycline (MIC = 2 μg/ml for both) and one was susceptible to tobramycin.
Clinical characteristics of patients with colistin-resistant, carbapenem-resistant K. pneumoniae, Detroit, MI, 27 July to 22 August 2009
Isolates were from hospitals A and B and from one LTAC facility (Fig. ). The index patient (patient 1, Fig. ) was identified in hospital A on outbreak day 0 (week 17 in Fig. ). Twenty days later (on outbreak day 20), patient 2 was identified at hospital B and patient 3 was identified at the LTAC facility. On day 25 and day 26, patients 4 and 5 were identified at hospital A. All of the patients, at some point, had stayed at hospital A, and patients 2, 3, and 5 had also stayed in the LTAC facility attached to hospital A. The mean number of opportunities for transmission between patients was 2.3 ± 0.5, and each patient had at least one opportunity for transmission involving one of the other patients. Figure represents the time line and transmission opportunities for the patients. The order in which patients are presented does not necessarily reflect the true chronological sequence in which patients actually acquired the organism but is based on temporal isolation of the organism from a clinical culture.
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 (more ...)
The PFGE and Rep-PCR analysis results are displayed in Fig. A and B, respectively. Both methods reveal that there are two clones (I and II). Four of the five colistin-resistant, carbapenem-resistant K. pneumoniae isolates belonged to a single clone designated clone II (Fig. ). This clone consisted of isolates 1, 3, 4, and 5 from Table and Fig. . There was a second clone of carbapenem-resistant K. pneumoniae at DMC, designated clone I (Fig. ), which included the fifth colistin-resistant case (case 2 in Table and Fig. ), and “representative” colistin-susceptible, carbapenem-resistant K. pneumoniae from DMC (isolates 29 and 52, Fig. ). Immunoblotting revealed that there is increased expression of KPC β-lactamase in clone II compared to that in clone I (Fig. ).
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 (more ...)
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 (more ...)
Once the cluster was recognized, infection control practices were enforced at all three study institutions. Patients were subjected to strict contact precautions, in single-occupancy rooms with dedicated staff, and infection control preventionists educated health care workers regarding the importance of hand hygiene and strict adherence to precautions. Infection control interventions were implemented, including active surveillance culturing (rectal) of all patients who were exposed to case patients and/or were in the same patient care unit as case patients. Overall, 112 surveillance rectal cultures were obtained and none revealed colistin-resistant, carbapenem-resistant K. pneumoniae. All patients admitted from LTAC facilities to a DMC facility were empirically subjected to contact precautions, and surveillance cultures for carbapenem-resistant Enterobacteriaceae were obtained. At the LTAC facility, infection control interventions included active surveillance of all new admissions to the LTAC facility, cohorting of patients who were culture positive for carbapenem-resistant Enterobacteriaceae, and initiation of daily baths with chlorhexidine (2%) for all LTAC facility patients. Additional colistin-resistant, carbapenem-resistant Enterobacteriaceae cases were not reported from DMC hospitals in the subsequent months.
When the 5 colistin-resistant, carbapenem-resistant K. pneumoniae case patients were compared to 60 patients with colistin-susceptible, carbapenem-resistant K. pneumoniae, the MIC to imipenem was significantly higher for case patients (a median of 64 μg/ml versus a median of 2 μg/ml; P < 0.001 between groups). The mean age of case patients was greater than the mean age of patients with colistin-susceptible, carbapenem-resistant K. pneumoniae (77 ± 6 years and 62 ± 8 years, respectively, P = 0.05). The mortality rate and length of hospital stay were higher among case patients than among controls, though these differences did not reach statistical significance (mortality rates were 40% and 26% for case patients and controls, respectively, and the mean lengths of hospital stay were 33 ± 23 days and 30 ± 23 days, respectively; P > 0.05 for both comparisons). All five case patients had cocolonization with a nonfermenter; three were cocolonized with P. aeruginosa, and two were cocolonized with A. baumannii. In contrast, only 23 (38%) of 60 controls were cocolonized with a nonfermenter (odds ratio, 2.44; 95% confidence interval, 1.8 to 3.3; P = 0.01). The two cocolonizing strains of A. baumannii were not resistant to colistin, and the three P. aeruginosa isolates were not tested for colistin susceptibility. All five nonfermenters had MICs of >32 μg/ml to imipenem.
Colistin use during the 3-month period prior to the outbreak (1 April to 30 June 2009) did not differ from that in the previous quarter (1 January to 31 March 2009) (mean DDD, 20.7 ± 3.4/1,000 patient days for the entire 18 months studied). None of the five patients received colistin in the 3 months preceding their colistin-resistant, carbapenem-resistant K. pneumoniae isolation. Polymyxin B had rarely been used at DMC in the past 4 years.