Carbapenems - Resistance and optimal methods in detection of Carbapenemases

Dr.T.V.Rao MD

Carbapenems are β lactam antibiotics, as are penicillins and cephalosporins, but

differ from these other classes in their exact chemical structure. Carbapenem use has increased as a

result of the rising resistance to cephalosporin antibiotics in Enterobacteriaceae (Escherichia coli,

Klebsiella, Enterobacter, and related genera). Carbapenems continues to be only available option in

many serious patients, and used with or without support of Microbiology Departments by

Physicians. Growing resistance to Cephalosporins limiting the options of antibiotic therapy as the

cephalosporin resistance is largely due to the spread of extended spectrum β lactamases (ESBLs),

which hydrolyse cephalosporins.1 ESBL producers are associated with poor clinical outcomes in

severe infections: a meta-analysis found that bacteraemia caused by bacteria with these enzymes

had 1.85-fold increased mortality , reflecting extended delays before effective therapy was

initiated.2 ESBLs now occur in 10–12% of E coli from in 50–80% of those in India and China, with

many ESBL producing strains also resistant to quinolones and aminoglycosides. Carbapenemases

detection by Disc diffusion methods alone is not fully protective. Confirmatory testing for KPC-

producing bacteria is recommended in geographical locations where Enterobacteriaceae are noted

to have decreased susceptibility to Carbapenems or resistance to most non-carbapenem beta-

lactams by routine testing. The most easily performed confirmatory test for KPCs is the modified

Hodge test, which has been found to be 100% sensitive for the detection of a carbapenemases,

although not specific for KPC production.; hence detection elevated MICs may be indicative to be

definite about the emerging resistance and we have to depend on Minimal inhibitory concentration

method from patients under critical care. To be fully protective and optimal, Molecular methods are

the fastest and most reliable way to detect and identify carbapenemases. Nucleic acid amplification

tests (NAATs) can definitively indicate and identify carbapenemases present. The use of NAATS

provides more definitive result 48 hours quicker. Definite confirmation of KPC production requires

molecular methods such as PCR, but these are costly and rarely available outside of reference

laboratories knowing the resistance patterns of an organism have implications beyond just the

treatment of the patient. A carbapenemases bearing GNB can spread throughout wards and

hospitals and can claim the lives of many patients beyond the index case. This needs improvement

of hygienic practices; because carbapenem resistance is a multi-mechanism process, they are

capable of resisting many disinfection protocols. Barrier precautions must be put in place to prevent

transmission to other patients.

Email doctortvrao@gmail.com