BackgroundThe World Health Organization recommends universal drug susceptibility
testing for Mycobacterium tuberculosis complex to guide
treatment decisions and improve outcomes. We assessed whether DNA sequencing
can accurately predict antibiotic susceptibility profiles for first-line
anti-tuberculosis drugs. MethodsWhole-genome sequences and associated phenotypes to isoniazid, rifampicin,
ethambutol and pyrazinamide were obtained for isolates from 16 countries
across six continents. For each isolate, mutations associated with
drug-resistance and drug-susceptibility were identified across nine genes,
and individual phenotypes were predicted unless mutations of unknown
association were also present. To identify how whole-genome sequencing might
direct first-line drug therapy, complete susceptibility profiles were
predicted. These were predicted to be pan-susceptible if predicted
susceptible to isoniazid and to other drugs, or contained mutations of
unknown association in genes affecting these other drugs. We simulated how
negative predictive value changed with drug-resistance prevalence.Results10,209 isolates were analysed. The greatest proportion of phenotypes were
predicted for rifampicin (9,660/10,130; (95.4%)) and the lowest for
ethambutol (8,794/9,794; (89.8%)). Isoniazid, rifampicin, ethambutol and
pyrazinamide resistance was correctly predicted with 97.1%, 97.5% 94.6% and
91.3% sensitivity, and susceptibility with 99.0%, 98.8%, 93.6% and 96.8%
specificity, respectively. 5,250 (89.5%) drug profiles were correctly
predicted for 5,865/7,516 (78.0%) isolates with complete phenotypic
profiles. Among these, 3,952/4,037 (97.9%) predictions of pan-susceptibility
were correct. The negative predictive value for 97.5% of simulated drug
profiles exceeded 95% where the prevalence of drug-resistance was below
47.0%. ConclusionsPhenotypic testing for first-line drugs can be phased down in favour of DNA
sequencing to guide anti- tuberculosis drug therapy.
The combination of amoxicillin/clavulanate plus meropenem is active against MDR/XDR-TB in vitro, and this triple therapy could be a useful therapy for MDR/XDR-TB and possibly help to reduce the development of further resistance. The drug susceptibility technique used here is routinely used, with modification, in mycobacteriology laboratories.
An 88-year-old man, receiving prednisolone for sarcoidosis, presented with a discrete keratotic lesion on the dorsum of his right hand following the placement of an intravenous cannula a month prior to its appearance. Medicopsis romeroi was isolated from the tissue and identified by sequencing the internal transcribed spacer region ITS-1 and the D1-2 fragment of the 28S rDNA gene. Histopathological examination showed fungal hyphae in the internal inflammatory cells layer and within the histocyte-macrophage layer, highly suggestive of deep mycosis. The patient was successfully treated with surgical excision of the cyst. M. romeroi exhibited high MIC values for echinocandin drugs in vitro, but appeared susceptible to newer triazole agents, amphotericin B and terbinafine. This is the first report of a subcutaneous phaeohyphomycotic cyst occurring following the placement of an intravenous cannula. This report highlights the potential role of M. romeroi as an emerging cause of deep, non-mycetomatous infection in immunocompromised patients.
We performed a retrospective study of clinical, epidemiological and microbiological characteristics of patients with confirmed Mycobacterium bovis infection treated at Francisco Muñiz Hospital, Buenos Aires, Argentina, between 1996 and 2008. A total of 39 patients were included, accounting for 0.4% of tuberculosis cases in our hospital. Of these, 93% had at least one risk factor for M. bovis; the most frequent was occupational exposure (65%), followed by history of living in a rural area (31%) and consumption of unpasteurised milk (4%). Pulmonary disease was the most frequent clinical presentation. Rifampicin resistance and multidrug resistance were seen in two patients, both of whom had human immunodeficiency virus infection.
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