The efficient detection and distinction of carbapenem-resistant and carbapenemase-producing Enterobacteriaceae continues to pose a major challenge to clinical microbiology laboratories, particularly in resource-constrained countries. Disc diffusion (DD), micro-broth dilution (BMD), Vitek II, Carba NP test, modified Hodge’s test (MHT) and real-time PCR were evaluated on known carbapenem-resistant and carbapenemase-producing clinical Enterobacteriaceae isolates in terms of their sensitivity and specificity using whole genome sequencing (WGS) as the gold standard. DD with meropenem (MRP), real-time PCR, DD with imipenem (IMP), BMD, Carba NP test, and BMD with IMP had sensitivities of 100%, 97.96%, 97.96%, 97.96%, 95.92%, and 95.92% respectively. Real-time PCR and Carba NP test had the highest specificities (100%) and shortest turnaround times (< 3 hours). DD or BMD using meropenem, followed by Carba NP test and PCR were the best protocols for detecting and confirming CPEs clinically. We recommend the Carba NP test and/or DD specifically for resource-constrained laboratories for detection and control of carbapenemase-producing Enterobacteriaceae.