Klebsiella pneumoniae Carbapenamase (KPC) Outbreak in a Multispeciality Cancer Hospital—An Emerging Superbug

Aim: To identify, analyse and control the outbreak of Carbapenamase producing Klebsiella pneumoniae. Objectives: 1) To detect multidrug resistant K. pneumoniae at the earliest and isolate patients. 2) To find out the predisposing causes for the occurrence of this outbreak. 3) To break the chain of infection transmission. 4) To reduce the risk of Hospital acquired infections. Methods: This retrospective study along with the surveillance was conducted from January 2017 to March 2017 at HCG multispecialty cancer hospital, Bangalore, India. Results: Total 15 patients were diagnosed with KPC infection during the first month of the study period. Those affected were mostly Male patients (73%), admitted in ICU (73%) for further treatment. In our study, the incidence of KPC infection was mostly found with bloodstream infections (60%), mostly seen in those with central lines (80%) followed by patients on ventilatory support (66%). Before the outbreak of KPC infection, all the patients (100%) had already been treated with higher antibiotics including Carbapenems. In our study, only nine out of fifteen patients (60%) could be salvaged with treatment and were discharged. Conclusions: Hospital Infection Control Committee’s regular screening and the training of healthcare professionals are vital for the control of the outbreak.


Background
Hospital acquired infections (HAI) especially pan-drug resistant infections are the most notorious infection encountered in multi speciality cancer hospitals with major implications like increased morbidity, mortality, financial burden and longer duration of hospital stay. Among the pan drug resistant infections, Klebsiella Pneumoniae Carbapenamase (KPC) is one of the emerging and challenging bugs in our setting. As per the worldwide data, KPC-producing Enterobacteriaceae were first reported in a clinical specimen from a patient in North Carolina in 2001 [1].
In the United States of America, the dissemination of KPC producing CRE isolates appeared to be clonal [2]. A sample of KPC-producing K. pneumoniae isolates sent to the CDC for reference testing from 1996 to 2008 was characterized using PFGE and multilocus sequence typing (MLST). This analysis revealed that a dominant strain, ST258, accounted for approximately 70% of all KPC-producing K. pneumoniae isolates sent to the CDC during that time period [2]. As per the Indian data, in 2009 a novel MBL, the New Delhi MBL (NDM), was described [3]. NDM was first identified in a K. pneumoniae isolate from a Swedish patient who had received medical care in India and was soon recognized as an emerging mechanism of resistance in multiple species of Enterobacteriaceae in the United Kingdom. Our hospital data shows that there is a seasonal trend of outbreaks of KPC with occasional 1 or 2 cases per month.
Antibiotics treatments for KPC are very limited and include Aminoglycosides, Colistin, Tigecycline and Fosfomycin [4] [5]. The activity of these antibiotics against KPC seems to depend on pk/pd parameters [6] [7] [8]. Irrational use and abuse of these higher antibiotics have been a major concern especially in developing countries which have lead to the emergence of Gram-negative isolates resistant to these agents [9] [10] [11].
Klebsiella pneumoniae is one of these multidrug resistant organisms (MDR) identified as an urgent threat to human health by the World Health Organization, the US Centers for Disease Control. The lineage defined as sequence type (ST) 258 is a notorious example of MDR K. pneumoniae. ST-258 frequently carries the K. pneumoniae carbapenemase (KPC) gene, as well as numerous other acquired AMR determinants, and has been responsible for outbreaks on several continents [12]. Our hospital, being a multi speciality cancer hospital, deals with immunocompromised patients and KPC infection shows a higher mortality rate.
According to Grinbaum [13], "One of the objectives of Epidemiological Surveillance carried out by the Hospital Infection Control Service is to detect outbreaks before the propagation results in further harm." We have a similar body, named Hospital Infection Control Committee (HICC) which is a committee responsible to investigate the outbreaks that include the source of the agent, means of transmission and control measures.
Minor breach in the prevention and control measure leads to an outbreak of any infection and the most common route of transmission of nosocomial infec-

Material and Methods
This  antibiotics.
An investigational proforma was created, which included patient identification, duration of hospitalization, culture reports as well as above selected predisposing factors. All the tests were done on automated Blood Culture System (Bact Alert) for blood and other samples were processed on routine media and then subjected to automated Vitek 2 Compactor identification and antibiotic sensitivity pattern with MIC's value. After the collection of reports statistical analysis was done using SPSS Software.    Apparently there was colonization of Klebsiella pneumoniae, and all healthcare professional were asymptomatic.

Results
The only limitation of this study was inability to do a detailed PCR study of the organism for comparison of isolates.

Discussion
K. pneumoniae, is a part of the respiratory and intestinal microflora of humans and can be isolated from the oropharyngeal cavity at a frequency up to 6%. It is strongly associated with infections, such as pneumonia, urinary infections and septicemias. Between half and three-quarters of all the bacteremias caused by this agent originate in the hospital, therefore they are resistant to ampicillin and carbenicillin, and are frequently susceptible to cephalosporins, cotrimoxazole, aminoglycosides and carbapenem [14]. Later due to genetic material exchange by plasmids and transposons, these organisms become resistant to higher antibiotics including carbapenems. This pattern was also found in our study, as the HAI cases were caused by ampicillin-resistant K. pneumoniae.
Most of these infections occurred in Tower 3 of our hospital which included high risk area consisting of Surgical ward, Hematology ward and ICU having critical patients who had undergone surgery, chemotherapy and immunosuppressant medicines. The first case among these patients was an international patient with diagnosis of blood cancer (AML) admitted in ICU. Since there was inability to perform molecular testing of KPC so the above mentioned patient could not be identified as an Index case in our study. After the implementation of surveillance strategies and adoption of the intervention measures, marked reduction in the infection rate was observed with only four cases reported in April and one in June as described in Table 5 and Figure   2. This justifies the appropriate adoption of intervention measures to control the outbreak and interruption of transmission chain. A fall in the incidence of Hospital infections was also observed when compared with indices prior to the outbreak. Quality Improvement Program (QIP) report was prepared and implemented for next three months. We have also started Infection Board Meeting   The mortality rate of carbapenem-resistant Klebsiella pneumoniae (CRKp) infections in North America, South America, Europe, and Asia is reportedly 33.24%, 46.71%, 50.06%, and 44.82%, respectively [15] which was similar to our mortality rate of 40%.

Conclusions
Despite of our efforts, the source of this agent couldn't be identified however we came to a conclusion that cross contamination of the organism was the major determinant for this outbreak during the patients care. Hospital Infection Control Committee's regular screening and the training of healthcare professionals are vital for the control of the outbreak. The determining factor of the outbreak appears to have been hand hygiene since after the intervention measure techniques, the outbreak was controlled. Target of more than 90% hand hygiene compliance of the healthcare professionals has been set and training/practices are going on. Antimicrobial stewardship has been suggested as an important part of efforts to control multidrug resistant organisms.
Funding: This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.