ABSTRACT
Despite vaccination programs and antivirals, influenza remains a prominent cause of morbidity and mortality. The Xpert Xpress Flu/respiratory syncytial virus (RSV) test is a leading influenza point-of-care test, but its evaluation has been limited to nasopharyngeal samples. In addition, the clinical impacts of Xpress Flu/RSV have not yet been quantified. We evaluated the performance of Xpress Flu/RSV at three locations in a UK Hospital Trust against an existing laboratory assay. Multiple upper respiratory tract sample types were included. In addition, we calculated time saved by Xpert, and the associations between Xpert use and rates of early patient isolation and antiviral prescription as recorded at the time of the laboratory result being telephoned out. A total of 642 patients were included in the diagnostic performance analysis. There were 177 laboratory-confirmed cases of influenza A, 7 influenza B and 86 RSV. For influenza A, sensitivity and specificity were 96.6% (95% confidence interval [CI]: 92.8%-98.8%) and 98.1% (CI: 96.4%-99.1%), respectively. This was sustained across all locations and sample types. The negative predictive value was 98.7% (CI: 97.2%-99.4%). The median amount of time saved was 27.1 h. Xpert use was associated with sixfold higher rates of isolation and threefold higher rates of antiviral prescribing by the time the laboratory result was available. Sensitivity for RSV was lower at 86.0% (95% CI: 76.9%-92.6%). Xpert Xpress Flu/RSV reliably detects influenza A infection and has significant clinical impacts. Cartridge optimization is required to enable accurate multiplexing, including from a range of sample types.
Subject(s)
Hospitals/statistics & numerical data , Influenza, Human/diagnosis , Point-of-Care Testing , Respiratory Syncytial Virus Infections/diagnosis , Adult , Antiviral Agents/therapeutic use , Child , Humans , Influenza A virus/isolation & purification , Influenza B virus/isolation & purification , Influenza, Human/drug therapy , Nasopharynx/virology , Patient Isolation/statistics & numerical data , Respiratory Syncytial Virus Infections/drug therapy , Respiratory Syncytial Virus, Human/isolation & purification , Sensitivity and Specificity , Time Factors , United KingdomABSTRACT
Genomic islands (GIs) are discrete gene clusters encoding for a variety of functions including antibiotic and heavy metal resistance, some of which are tightly associated to lineages of the core genome phylogenetic tree. We have investigated the functions of two distinct integrase genes in the mobilization of two metal resistant GIs, G08 and G62, of Acinetobacter baumannii. Real-time PCR demonstrated integrase-dependent GI excision, utilizing isopropyl ß-d-1-thiogalactopyranoside IPTG-inducible integrase genes in plasmid-based mini-GIs in Escherichia coli. In A. baumannii, integrase-dependent excision of the original chromosomal GIs could be observed after mitomycin C induction. In both E. coli plasmids and A. baumannii chromosome, the rate of excision and circularization was found to be dependent on the expression level of the integrases. Susceptibility testing in A. baumannii strain ATCC 17978, A424, and their respective ΔG62 and ΔG08 mutants confirmed the contribution of the GI-encoded efflux transporters to heavy metal decreased susceptibility. In summary, the data evidenced the functionality of two integrases in the excision and circularization of the two Acinetobacter heavy-metal resistance GIs, G08 and G62, in E. coli, as well as when chromosomally located in their natural host. These recombination events occur at different frequencies resulting in genome plasticity and may participate in the spread of resistance determinants in A. baumannii.