Summary

Anti-microbial drugs of β-lactam class are routinely used for the treatment of infections caused by the Gram-negative bacteria like Escherichia coli, Klebsiella pneumonia, and Enterobacter cloacae in the Family Enterobacteriaceae. Unfortunately, Enterobacteria resistant to β-lactam antibiotics have evolved and disseminated worldwide including Sri Lanka. In particular, carbapenem resistant enterobacteria can cause life-threatening infections as they are resistant to carbapenems, the last line β-lactam antibiotics available against such pathogens. An alarming number of incidences of carbapenemase producing enterobacteria (CPE) have been reported in Sri Lanka. Especially, the presence of NDM-1, NDM-4, and OXA-181 type carbapenemases has been confirmed in. K. pneumoniae and Enterobacter cloacae isolated from the hospitalized patients in Sri Lanka. However, the available molecular data on CPE are neither completed nor up to date. Therefore, comprehensive molecular level studies are needed to determine the current status of the carbapenem resistance in Sri Lanka.

Sri Lanka has always been in greater risk of acquiring multidrug resistant enterobacteria due to increase travel between CPE endemic countries like India and Middle East. These countries are believed to serve as reservoirs for NDM-1 and OXA-181 CPE. Therefore, timely identification of CPE is utmost important for the implementation of better infection control measures. In addition, early identification of the infections caused by CPE is crucial for the successful patient management.

Polymerase chain reaction (PCR) based molecular identification is considered as the gold standard for carbapenamase characterization. However, molecular procedures are costly and require expensive instruments and trained personals. In addition, other available microbiological investigations for the detection of CPE are time consuming and suffer from lack of sensitivity against NDM type CPE. Therefore, a cost effective and prompt CPE detection method is needed. In that regard, the biochemical method developed by Nordman et. al. seems to fulfill the requirements of a suitable CPE detection test. This method could be adapted to Sri Lanka as a potential low cost, rapid CPE detection test after a systematic evaluation and proper validation.

Objectives

1. Overall aim

   To characterize the carbapenemase producing clinically significant enterobacteria (CPE) and to validate a low-cost protocol for the rapid detection of CPE in Sri Lanka.

2. Specific objectives:

   1. To determine the antibiotic sensitivity pattern of enterobacteria isolated form different clinical samples.
   2. To determine the regional prevalence of ESBL and carbapenemase producers among antibiotic resistant enterobacteria isolates
   3. To determine the molecular identity of the carbapenemase present in each CPE.
   4. To characterize the variants of carbapenemases with emphasis on NDM and OXA-48 type enzymes
   5. To optimize a rapid biochemical test for the detection of CPE isolates found in Sri Lanka
   6. To compare the sensitivity, specificity and cost of the rapid test with the existing CPE detection tests.

Major Equipment Facilitated by Grant