Accuracy And Applicability Of Different Phenotypic Methods For Carbapenemase Detection In Enterobacteriaceae:A Systematic Review And Meta-analysis

BackgroundInfections caused by carbapenem-resistant Enterobacteriaceae(CRE)are tough medical problems,and the world-wide prevalence of CRE is a major public health threat.The most important mechanism of resistance to carbapenems in CRE is the production of cabarpenemases.Compared to CRE caused by other mechanisms,carbapenemase-producing Enterobacteriaceae(CPE)are more virulent and easier to horizontally transmit,indicating extremely high morbidity and mortality.Therefore,early and accurate detection of CPE is essential for antibiotic management and infection control.However,there are many types of CPE detection methods,and how to choose has become a problem that clinical laboratories must consider and solve.ObjectivesThe aim of this systematic review was to assess the accuracy of the modified Hodge test(MHT),carbapenemase Nordmann-Poirel test(CarbaNP),modified carbapenem inactivation method(mCIM)and matrix-assisted laser desorption ionization – time of flight mass spectrometry(MALDI-TOF-MS)for CPE detection;and to evaluate the applicability of these methods from the point of view of economic factors,human resources,and clinical efficiencies so as to provide a basis for the laboratory to choose the appropriate CPE detection method.MethodsWe searched Pub Med,EMBASE,Google Scholar,Cochrane Library,China National Knowledge Infrastructure(CNKI),Sinomed,Wan fang database and VIP database until March,2019 for studies that met the inclusion criteria.The QUADAS-2 tool was used for quality assessment.The meta-analysis included pooled sensitivity,specificity,diagnostic odds ratio,summary receiver operating characteristic(SROC)curve,and area under the curve(AUC).The relative ratio of diagnostic odds ratio was calculated to indicate the indirect comparison of the accuracy of different diagnostic methods by meta-regression analysis.The I2 and Q-test were used to determine study heterogeneity,and logistic meta-regression was employed to identify the potential causes.Deek’s funnel plot and Duval’s trim and fill method were performed to detect publication bias.Sensitivity analysis was conducted to evaluate the robustness of the meta-analysis.Results54 studies were included for the analysis.The pooled sensitivities andspecificities of MHT,Carba NP,mCIM,and MALDI-TOF MS were respectively 92%(95% CI: 87%-95%)and 93%(95% CI: 86%-97%),97%(95%CI: 94%-98%)and 100%(95% CI: 99%-100%),99%(95% CI:99%-100%)and 99%(95% CI: 96%-100%),and 99%(95% CI: 96%-100%)and 99%(95% CI: 96%-100%).The pooled diagnostic odds ratios of MHT,Carba NP,mCIM and MALDI-TOF MS were 98.156(95% CI:48.175-199.995),1277.710(95%CI: 751.391-2172.692),3597.352(95%CI: 1287.575-10000),and 1781.360(95% CI: 651.827-4868.228),respectively;The pooled AUC values of the SROC were 0.97,1,1,and 1,respectively.Carba NP,mCIM and MALDI-TOF MS showed better diagnostic performances than MHT(p=0.00 for Carba NP vs MHT,p=0.00 for MADLI-TOF-MS vs MHT,p=0.00 for mCIM vs MHT).ConclusionsCarba NP,mCIM and MALDI-TOF MS all demonstrated high accuracies in CPE detection,while MHT was not recommended due to some clear drawbacks.We recommended the selection of carbapenemase detection tests in the order of mCIM,Carba NP and MALDI-TOF MS according to their simplicities,costs and the equipments and skills involved.