Large hospital outbreak of KPC-2-producing Klebsiella pneumoniae: investigating mortality and the impact of screening for KPC-2 with polymerase chain reaction

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Summary

Background

Multi-drug-resistant Klebsiella pneumoniae carbapenemase (KPC)-2-producing K. pneumoniae are an increasing cause of healthcare-associated infections worldwide.

Aims

To investigate the impact of clinical infection on mortality, and examine the effect of use of KPC-2-specific polymerase chain reaction (PCR) on the time to contact isolation during an outbreak.

Methods

Cases were defined as patients clinically infected or colonized with KPC-2-producing K. pneumoniae between June 2010 and July 2012. Cases were described by demographic and health characteristics, and the association between infection and mortality, adjusted for comorbidities and demographic characteristics, was determined using Poisson regression with robust standard errors. A comparison was made between the time to contact isolation with a culture-based method and PCR using Wilcoxon's rank sum test.

Findings

Of 72 cases detected, 17 (24%) had undergone transplantation and 21 (29%) had a malignancy. Overall, 35 (49%) cases were clinically infected, with pneumonia and sepsis being the most common infections. Infection was an independent risk factor for mortality (risk ratio 1.67, 95% confidence interval 0.99–2.82). The median time to contact isolation was 1.5 days (range 0–21 days) using PCR and 5.0 days (range 0–39 days) using culture-based methods (P = 0.003). Intermittent negative tests were observed in 48% (14/29) of cases tested using culture-based methods.

Conclusion

KPC-2-producing K. pneumoniae mainly affect severely ill patients. Half of the cases developed clinical infection, associated with increased risk of death. As PCR accelerates isolation and provides the opportunity for preventive measures in colonized cases, its use should be implemented promptly during outbreaks. Further studies are needed to enhance knowledge about KPC detection patterns and to adjust screening guidelines.

Introduction

Klebsiella pneumoniae carbapenemase (KPC), conferring carbapenem resistance to Enterobacteriaceae, are an emerging public health concern.1, 2 The variants KPC-2 and KPC-3 are typically responsible for outbreaks. They are mainly identified from K. pneumoniae isolates, which primarily affect severely ill patients.1, 3, 4, 5 The lack of effective antibiotics (limited to colistin, tigecycline, fosfomycin and aminoglycosides) to fight infections caused by these multi-drug-resistant pathogens contributes to the reported high mortality.3, 5, 6 However, patient comorbidities need to be considered when estimating KPC-related morbidity and mortality.

Sensitive polymerase chain reaction (PCR)-based techniques for the detection of carbapenemase-producing Enterobacteriaceae have been developed as an alternative to culture-based methods. However, their use is limited because they only capture some of the known carbapenemases, they are costly, and they require specific technical knowledge and equipment.2, 7, 8

Faecal samples, and rectal and perirectal swabs are primarily used for KPC screening. Optimal screening frequency needs to consider the local prevalence of the micro-organism, patient colonization risk and case mix.9 Also, deciding on the timing and interval between screenings is problematic because colonized cases may have negative results in between positive results.10, 11, 12 Thus, improved knowledge on excretion patterns is critical to develop evidence-based recommendations regarding screening.

The prevalence of KPC-2-producing K. pneumoniae in Germany is low, with <1% of invasive K. pneumoniae isolates presenting with carbapenem resistance in 2012.13 However, over almost three years, KPC-2-producing K. pneumoniae belonging to the worldwide disseminated ST258 clone spread amongst patients in a tertiary care hospital with a capacity of 1300 beds, including 58 beds in the surgical intensive care unit.14 Screening was limited until the end of May 2012, when systematic weekly screening was implemented for contact patients and patients hospitalized on affected wards for ≥14 days, and all patients were screened at hospital admission. In parallel, antimicrobial stewardship was reinforced and infection control measures (strict barrier precautions, improved hand hygiene, cohorting of cases and separation of contacts) were intensified.

Although the outbreak was partially contained, 22 further cases were detected after July 2012, the last of which was detected in April 2013. The main route of transmission was probably from person to person, including intermediate vectors such as contaminated hands and the environment. This study covers the first 25 months of this outbreak.

This study aims to describe the impact of KPC-2-producing K. pneumoniae infection compared with colonization on mortality and length of hospital stay (LOS) among cases detected between 28th June 2010 (date of admission of the index case) and 31st July 2012. During the outbreak, culture-based methods for the detection of KPC-2-producing K. pneumoniae were supplemented with KPC-2-specific PCR. The effect of this change on the detection of new cases and time to contact isolation was analysed. In some confirmed cases, KPC-2 was only detected intermittently, and these episodes are described in order to contribute to enhanced knowledge about detection patterns for KPC-2-producing K. pneumoniae.

Section snippets

Methods

A case was defined as any hospitalized patient in whom KPC-2-producing K. pneumoniae was isolated from a clinical or screening sample between 28th June 2010 and 31st July 2012. KPC-2-producing K. pneumoniae colonization or infection was determined by isolation of the pathogen, using chromogenic agar plates (CHROMagar KPC plates, CHROMagar, Paris, France), or by at least two consecutive positive KPC-2-specific PCR tests from different specimens, available after 31st May 2012.15

Among isolates

Case characteristics

The index case was a patient transferred from a Greek hospital on 28th June 2010, from whom an isolate with KPC-2-producing K. pneumoniae was recovered 10 days later. By 31st July 2012, 71 further cases had been detected. The first KPC-2-producing K. pneumoniae isolate was recovered by culture-based methods in 61 (85%) cases, and by PCR in 11 (15%) cases. PFGE results were available for 63 (88%) of the 72 cases, and they had identical patterns. Four patients were excluded from this study on the

Discussion

In this hospital outbreak, KPC-2-producing K. pneumoniae were mainly isolated from patients with severe underlying illnesses. Clinical infection developed in half of the cases, and was associated with increased mortality and LOS. Since the introduction of direct KPC-2-specific PCR, time to contact isolation decreased significantly. Half of the cases with tests performed by culture-based methods presented intermittent negative test results. The outbreak was probably triggered by a patient

Acknowledgements

The authors would like to thank Anja Behne, Heike Hannemann, Karsta Angela Weis and Gudrun Wendland from Leipzig University Hospital, and Lisa Prinz for their contribution to data collection and data entry.

References (31)

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