Background
Carbapenem-resistant Enterobacteriaceae (CRE) infections are increasing worldwide and OXA 48-like carbapenemases are a significant cause of resistance.oxa 48 The OXA 48-type carbapenemases hydrolyze both extended-spectrum cephalosporins and carbapenems, which are important for treatment of serious infections including sepsis and pneumonia.oxa 48 The OXA family of carbapenemases includes several sequence variants, including OXA-48, OXA-181, and OXA-232. They can be horizontally transmissible via plasmids and appear to have originated as gene escapes from the Shewenella genus chromosomes (1).
OXA 48-like carbapenemases have a high specificity for carbapenems and low activity against extended-spectrum cephalosporins, but they have weaker activity than other carbapenemases.oxa 48 They can hydrolyze aztreonam and imipenem, which have broad clinical use and are effective against multidrug-resistant Gram-negative organisms, including CRE.
Infections due to OXA 48-like carbapenemases typically affect hospitalized patients with underlying illnesses, and they are more common in older patients.oxa 48 Infection rates are higher in individuals who have undergone interhospital transfers and those who undergo invasive procedures during hospitalization, such as central line insertion. Infections caused by these organisms are difficult to treat because of the wide range of drugs that are ineffective against them (2).
PCR methods and inhibitor-based tests for carbapenemase production are used extensively in laboratories to identify these organisms, but the cost of these methods makes them impractical in clinical settings.oxa 48 An increase in sensitivity and specificity would be desirable, as would an inexpensive method of screening for OXA-48-like carbapenemases.
We developed a new, highly sensitive immunochromatographic lateral flow test (Carba NP) using an oligonucleotide primer set that detects two epitopes specific to OXA-48 and its sequence variants.oxa 48 The test can be performed in less than 20 minutes and has a sensitivity of 100% and a specificity of 99% for OXA-48 and its variants. The test also provides the ability to discriminate OXA-48 from other carbapenemases, including KPC and NDM-1.
The Carba NP test can be easily integrated into existing carbapenemase testing algorithms for routine clinical analysis of CRE in hospitals and LTCFs.oxa 48 In a pilot study, the test was applied to 92 K. pneumoniae isolates confirmed as OXA-48 producers collected from LTCF residents with bacteruria and/or pyuria. The results showed that the test had good sensitivity, specificity and stability over time, and could be used to identify OXA-48 producers in both K. pneumoniae and other species.
Infections attributed to OXA-48-producing organisms were treated successfully in 70-80% of cases with the combination of aztreonam/avibactam and amikacin.oxa 48 In addition, successful outcomes have been reported with aztreonam/avibactam alone in several cases. However, the emergence of resistance to these novel antibiotic combinations will impact therapeutic options for OXA-48-producing isolates. Further studies are needed to evaluate the efficacy of alternative therapies, such as the newer benzylpenicillins (ceftazidime-avibactam and cloxacillin/avibactam). These may be particularly useful in preventing the spread of CRE infections.