Advice
Clinical and technical evidence
Clinical and technical evidence
A literature search was carried out for this briefing in accordance with the published process and methods statement. This briefing includes the most relevant or best available published evidence relating to the clinical effectiveness of the technology. Further information about how the evidence for this briefing was selected is available on request by contacting mibs@nice.org.uk.
Published evidence
Four studies are summarised in this briefing: 1 comparative diagnostic performance study (Findlay et al. 2015), 2 diagnostic performance studies (Vergara et al. 2014; Garcia-Fernandez et al. 2015) and 1 proof-of-concept study (Hinic et al. 2015).
Table 3 summarises the clinical evidence as well as its strengths and limitations.
Strengths and limitations of the evidence
The available evidence on using the eazyplex SuperBug kits is currently limited to diagnostic performance studies. These studies did not evaluate diagnostic performance in a clinical setting, nor did they compare performance with an appropriate reference standard used in healthcare practice (microbiological culture). No studies were identified that reported clinical or healthcare-related outcomes.
Three studies used clinical bacterial isolates and 1 study used urine samples, which is not representative of current clinical practice that uses rectal or stool samples to detect carbapenemase-producing organisms (CPOs). The diagnostic performance results may therefore not be generalisable.
One specialist commentator highlighted that all of the studies assessed samples with a relatively high inoculum of bacteria. This raises questions about the assay's sensitivity when low inocula are present and when it is more difficult to concentrate the inoculum of CPOs from faecal material. They considered that for successful screening of rectal swabs, clinicians will need to be confident that low inocula can be detected and that faecal material is not interfering with assay performance.
Table 3 Summary of evidence
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Study size, design and location |
Intervention and comparators |
Outcomes |
Strengths and limitations |
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n=450 clinical isolates from various bacterial species Comparative diagnostic performance study UK |
The eazyplex SuperBug complete A kit, Xpert Carba-R and Check-Direct CPE (on 2 different platforms). These were compared with a reference standard using PCR assays and a commercial microarray (Check-MDR CT102). |
The overall test sensitivity and specificity were 95.5% and 100% respectively. The eazyplex SuperBug A was unable to detect 18% (18/102) OXA-48 variant carbapenemase genes. A modified eazyplex SuperBug complete B kit was later provided and correctly identified the 18 OXA-181 producers. |
A large panel of bacterial isolates were used, with carbapenemase-resistance mechanisms defined through appropriate methods. The distribution of the carbapenemases seen in this study did not mimic the natural distribution of carbapenemases because of the selection of isolates for carbapenemase diversity. No results other than the OXA-181 were reported for the eazyplex SuperBug complete B kit. |
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n=82 clinical isolates from Acinetobacter species Diagnostic performance study Spain |
The eazyplex SuperBug complete A kit (not explicitly stated but identified based on the range of carbapenemase genes). The presence of genes encoding carbapenemases was confirmed by PCR and DNA sequencing. |
The presence or absence of carbapenem-hydrolysing enzymes was correctly determined for all isolates except IMP2 and OXA-51, which are not detected by the eazyplex SuperBug complete A test. Unspecific DNA amplification was seen for 5 samples in the KPC, OXA-58 and OXA-40 reaction tubes, which accounted for false-positive results. |
The study was limited to only Acinetobacter baumannii strains of bacteria. No sensitivity or specificity results were reported. |
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Garcia-Fernandez et al. (2015) N=94 genotypically characterised carbapenemase-producing strains and 45 clinical isolates Diagnostic performance study Spain (2 centres) |
The eazyplex SuperBug CRE kit with the GENIE II platform. Conventional PCR assays and sequencing were used to characterise carbapenemase genes in the carbapenemase-producing strains. Identification of the carbapenemases in the clinical isolates was done by minimum inhibitory concentration profiles and the modified Hodge test. Double-disc synergy tests were done for ESBL identification. |
There was 100% agreement between the eazyplex SuperBug CRE system results and the PCR and sequencing results. For the contemporary isolates, 100% concordant results were found between the inferred phenotype and the eazyplex SuperBug CRE system results. Cycle threshold values for the genes detected ranged from 3 minutes 45 seconds to 9 minutes 45 seconds. |
A range of different micro-organisms was identified from both the carbapenemase-producing strains and the contemporary clinical isolates. There were no clinical isolates expressing more than 1 carbapenemase simultaneously. However, co-expressions of ESBLs and carbapenemases were identified. The study was done in Spain and so the distribution of the carbapenemases seen in this study may not mimic the distribution of carbapenemases in the UK. |
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n=50 urine samples (including 35 corresponding bacterial isolates) Proof-of-concept study Switzerland |
The eazyplex SuperBug CRE kit with the GENIE II platform. Phenotypic confirmation of ESBL production on culture isolates was done with Etest ESBL and AmpC strips (bioMerieux). |
The eazyplex test correctly identified CTX-M-1- and CTX-M-9-group-encoding genes in all 30 urine samples with confirmed ESBL production (sensitivity 100%). One out of 48 urine samples tested had a false-positive result (specificity 97.9%). Two urine samples gave invalid results because of multiple unspecific fluorescent signals. The analytical sensitivity for testing with the newly developed urine protocol was between 102 and 103 CFU/ml. |
The study only investigated the detection of ESBL-encoding genes. Results for the identification of carbapenemase-encoding genes and of co-expression with ESBL-encoding genes were tabulated but not discussed. No sensitivity or specificity values were reported for these. |
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Abbreviations: CFU, colony forming units; ESBL, extended-spectrum spectrum beta-lactamases; PCR, polymerase chain reaction. |
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