Evolving rapid methicillin-resistant Staphylococcus aureus detection: Cover all the bases

The dissemination of methicillin-resistant (MR) Staphylococcus aureus (SA) in community and health-care settings is of great concern and associated with high mortality and morbidity. Rapid detection of MRSA with short turnaround time can minimize the time to initiate appropriate therapy and further promote infection control. Early detection of MRSA directly from clinical samples is complicated by the frequent association of MRSA with methicillin-susceptible SA (MSSA) and coagulase-negative Staphylococcus (CoNS) species. Infection associated with true MRSA or MSSA is differentiated from CoNS, requires target specific primers for the presence of SA and mec A or nuc or fem A gene for confirmation of MR. Recently, livestock-associated MRSA carrying mec C variant complicates the epidemiology of MRSA further. Several commercial rapid molecular kits are available with a different combination of these targets for the detection of MRSA or MSSA. The claimed sensitivity and specificity of the currently available commercial kits is varying, because of the different target combination used for detection of SA and MR

Treatment failure in a UK malaria patient harbouring genetically variant Plasmodium falciparum from Uganda with reduced in vitro susceptibility to artemisinin and lumefantrine.

BACKGROUND: Recent cases of clinical failure in UK malaria patients treated with artemether-lumefantrine have implications for malaria chemotherapy worldwide. METHODS: Parasites were isolated from an index case of confirmed Plasmodium falciparum treatment failure after standard treatment, and from comparable travel-acquired UK malaria cases. Drug susceptibility in vitro and genotypes at six resistance-associated loci were determined for all parasite isolates and compared with clinical outcomes for each parasite donor. RESULTS: A traveller, who returned to the UK from Uganda in 2022 with Plasmodium falciparum malaria, twice failed treatment with full courses of artemether-lumefantrine. Parasites from the patient exhibited significantly reduced susceptibility to artemisinin (ring-stage survival 17.3%; 95% C.I. 13.6 - 21.1 %; P<0.0001) and lumefantrine (EC50 259.4nM; 95% C.I. 130.6-388.2nM; P=0.001). Parasite genotyping identified an allele of pfk13 encoding both the A675V variant in the Pfk13 propeller domain and a novel L145V non-propeller variant. In vitro susceptibility testing of six other P. falciparum lines of Ugandan origin identified reduced susceptibility to artemisinin and lumefantrine in one additional line, also from a 2022 treatment failure case. These parasites did not harbour a pfk13 propeller domain variant but rather the novel non-propeller variant T349I. Variant alleles of pfubp1, pfap2mu and pfcoronin were also identified among the seven parasite lines. CONCLUSIONS: We confirm, in a documented case of artemether-lumefantrine treatment failure imported from Uganda, the presence of pfk13 mutations encoding L145V and A675V. Parasites with reduced susceptibility to both artemisinin and lumefantrine may be emerging in Uganda