Klebsiella pneumoniae Carbapenemase: Extended-Spectrum beta-Lactamase Continues to Go Global

Luke F. Chen, MBBS, FRACP


February 12, 2009

In This Article

Infection Control and Treatment

The spread of KPC-producing organisms in the community and in the hospital environment represents a serious infection control and therapeutic challenge. Detection of KPC-harboring organisms was erratic before the recent adoption of ertapenem-based screening. McGettigan and colleagues[30] presented an abstract demonstrating that ertapenem susceptibility testing is highly sensitive (80%) but only moderately specific. Additionally, the same study demonstrated that imipenem and meropenem screening for KPC producers would miss approximately 50% of the KPC-producing organisms. In light of increasing supportive evidence, laboratories should switch over to ertapenem-based screening to improve detection for KPC-producing Gram-negative bacilli.

Containment of KPC-producing organisms has been a focus of intense study.

Several abstracts presented at the recent ICAAC/IDSA meeting highlighted the trials and tribulations involved in controlling outbreaks of KPC. Some effective strategies to control the spread of KPCs include (1) performing active surveillance for KPCs by perirectal swabs or stool cultures,[31] (2) cohorting KPC-colonized and KPC-infected patients,[31,32] (3) assigning dedicated nursing staff to cohort units,[31,32] and (4) intensifying hand hygiene and environmental cleaning.[31]

An example of success in controlling KPCs came from Kocher and colleagues[31] at SUNY Downstate Medical Center, Brooklyn, New York, who used a combination of these interventions in their ICU to curtail an outbreak of multidrug-resistant bacteria that included KPCs. The investigators obtained rectal swab cultures on all new admissions to the ICU and repeated the surveillance cultures weekly. KPC-infected or colonized patients were cohorted and assigned a dedicated group of nurses to care for them. Daily environmental cleaning was performed with a quaternary ammonium compound on all work surfaces in clinical areas. As a result of these interventions, the number of KPC infections/colonizations significantly decreased over the ensuing 12 months.

Despite the apparent effectiveness of some or all of the aforementioned interventions, questions remain about how patients should be screened for KPCs, whether or not contacts should be screened, and which laboratory method to use to screen patients for KPCs. The first question is easier to answer than the others. Kotlovsky and colleagues[33] compared the effectiveness, labor burden, and turnaround time of 3 laboratory methods to screen for KPC-producing organisms. Plating of rectal swab samples directly onto McConkey agar with imipenem and ertapenem discs provided accurate results within 24 hours of test initiation, and 96.5% concordance with the polymerase chain reaction (PCR) assay for KPC detection. Thus, the study authors recommended that unless KPC results are urgently required, direct plating onto agar with imipenem and ertapenem discs is the most accurate and cost-effective laboratory method to screen for KPCs.

The mortality associated with infection caused by KPC-producing organisms is estimated to be between 22% and 59%,[25,34] and many clinicians have resorted to the use of tigecycline and the polymyxins for treatment.[35] Limited experience and lack of familiarity with tigecycline have largely limited the use of this agent. Fortunately, most KPC-producing organisms remain exquisitely susceptible to tigecycline. Castanheira and colleagues[36] tested 178 isolates of KPC-producing organisms against tigecycline and found only 1 (0.6%) isolate that was not susceptible to tigecycline by standard CLSI broth microdilution methods.

Polymyxin B and colistin have been associated with high rates of nephrotoxicity and thus must be considered drugs of last resort. Emerging data have shown that the polymyxins may not be as nephrotoxic as previously believed. Despite this finding, polymyxins should only be used cautiously. Furthermore, there are increasing reports of polymyxin resistance in KPC-producing organisms.[36]


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