In the Sunday Times today, Editor at Large Han Fook Kwang wrote on the issue of overcharging by doctors and the healthcare industry, with one of the points being how the promotion of medical tourism in Singapore had perhaps also helped to promote such a culture (“Doctors v Doctors” – behind a paywall so I won’t link to the article). It’s an interesting issue that is pertinent to all doctors, and may well be worth a discussion another time when the heat has died down. Nonetheless, one of the major negative externalities that was either underemphasized or underestimated is the importation of pathogens from other healthcare systems in the region. Carbepenemase-producing Enterobacteriaceae (a really incomprehensible polysyllabic tongue-twister, so “CPE” for short) are the worst of the pathogens that have been imported into our healthcare system.

Enterobacteriaceae is a collective term for a large group of bacteria that colonize the intestines of humans and animals, several members (i.e. Escherichia coli, Klebsiella pneumoniae, Enterobacter spp., Salmonella spp., etc) of which are able to cause human disease under the right (or rather wrong) set of conditions. CPE are those Enterobacteriaceae that have acquired one or more of several genes that enable production of carbapenemases – enzymes that break down the carbapenem class of antibiotics, which were until recently the last-resort broadest-spectrum and most powerful antibiotics used for the treatment of life-threatening bacterial infections and those infections caused by many drug-resistant bacteria. If these CPE were resistant to carbapenems alone, that would not be such a big deal. But the vast majority of CPE have typically acquired resistance to multiple classes of antibiotics, rendering them virtually immune to antibiotic treatment, or else susceptible only to antibiotics that are either more toxic or less effective or (usually) both.

The first CPE in Singapore was actually described in 1998, isolated from an inpatient with hematological disease at the Singapore General Hospital. This particular strain of bacteria did not spread, and it was not until 2010 that epidemic strains of CPE were imported into Singapore. The first two cases – described in the Straits Times – were a Singapore resident who returned after having sought medical treatment in India, and a Bangladeshi national who had come to the Singapore General Hospital as a medical tourist. Within a month, there were four additional cases, and these were inpatients who had not recently traveled out of Singapore, signifying that the CPE had somehow been transmitted to them during their stay in the Singapore hospitals. These Enterobacteriaceae carried the New Delhi metallo-beta-lactamase (NDM-1) gene – first described in 2008 and conventionally named after its point of origin – a “pandemic” carbapenemase gene that has since been described in various Enterobacteriaceae and has spread worldwide out of its origins in the Indian subcontinent.

Since then, the number of patients with NDM-1-producing Enterobacteriaceae have increased virtually exponentially in local hospitals, and Enterobacteriaceae producing other carbapenemases have also been found, including those harbouring Klebsiella pneumoniae carbapenemase (KPC) and oxacillinases (OXA). Although the number of local patients infected and/or colonized by CPE locally are nowhere as high as those infected by other “superbugs” such as methicillin-resistant Staphylococcus aureus (MRSA), carbapenem-resistant Acinetobacter baumannii (CRAB), or extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, CPE has been found in the environment (likely sewage-contaminated), in seafood in a Chinese grocery store in Canada, and in farms. These are isolated reports, but nonetheless demonstrate the ability of CPE to survive and spread outside the hospital setting. It may merely be a matter of years before community-onset CPE infections occur in Singapore, just like ESBL-producing Enterobacteriaceae that can be found in persons in the local community with no history of healthcare contact.