Carbapenem Resistance in Gram-Negative Bacteria: The Not-So-Little Problem in the Little Red Dot

Abstract

Singapore is an international travel and medical hub and faces a genuine threat for import and dissemination of bacteria with broad-spectrum resistance. In this review, we described the current landscape and management of carbapenem resistance in Gram-negative bacteria (GNB) in Singapore. Notably, the number of carbapenem-resistant Enterobacteriaceae has exponentially increased in the past two years. Resistance is largely mediated by a variety of mechanisms. Polymyxin resistance has also emerged. Interestingly, two Escherichia coli isolates with plasmid-mediated mcr-1 genes have been detected. Evidently, surveillance and infection control becomes critical in the local setting where resistance is commonly related to plasmid-mediated mechanisms, such as carbapenemases. Combination antibiotic therapy has been proposed as a last-resort strategy in the treatment of extensively drug-resistant (XDR) GNB infections, and is widely adopted in Singapore. The diversity of carbapenemases encountered, however, presents complexities in both carbapenemase detection and the selection of optimal antibiotic combinations. One unique strategy introduced in Singapore is a prospective in vitro combination testing service, which aids physicians in the selection of individualized combinations. The outcome of this treatment strategy has been promising. Unlike countries with a predominant carbapenemase type, Singapore has to adopt management strategies which accounts for diversity in resistance mechanisms.

Keywords: antibiotic combinations; carbapenemase; extensively-drug resistant; infection control; molecular epidemiology.

Figure 1

(a) Number of non-duplicate key Gram-negative pathogens in Singapore General Hospital from 2011 to 2015; * includes data from the first 10 months; and (b) Carbapenem non-susceptibility rates (% intermediate and resistant) of non-duplicate key Gram-negative pathogens in Singapore General Hospital from 2011 to 2015; * includes data from the first 10 months.