Drug-resistant tuberculosis in Central Mozambique: the role of a rapid genotypic susceptibility testing.

BACKGROUND: Genotypic molecular testing may be very helpful for tuberculosis (TB) drug-resistance surveillance and for treatment guidance in low resource settings. METHODS: Descriptive analysis of M. tuberculosis isolates from Beira Central Hospital, Mozambique, during 2014-2015. Genotype MTBDRplus and MTBDRsl were used and patient medical records reviewed. To explore genotypic susceptibility profile of Mycobacterium tuberculosis, to first and second line drugs (SLD) in Beira Mozambique. RESULTS: Of 155 isolates, 16.1 % (25) were multidrug resistant (MDR), 8.4 % (13) isoniazid-monoresistant and 1.3 % (2) rifampicin-monoresistant. Among MDR-TB, 22.2 % showed primary and 77.8 % represented acquired resistance. The majority of patients with drug resistance had a history of previous TB treatment. Among 125 isolates tested for ethambutol and SLD, 7.2 % (9) were resistant to ethambutol, 4.8 % (6) to fluoroquinolones and 0.8 % (1) to ethambutol and fluoroquinolones. Resistance to injectable SLD was not detected. CONCLUSIONS: As far as we know this is the first report of a genotypic testing used to provide information about SLD resistance in Mozambique, where phenotypic susceptibility testing is usually unavailable. Extensively drug resistant TB was not detected in this isolates from Beira Mozambique.

Nosocomial Outbreak of Extensively Drug-Resistant (Polymyxin B and Carbapenem) Klebsiella pneumoniae in a Collapsed University Hospital Due to COVID-19 Pandemic.

We correlated clinical, epidemiological, microbiological, and genomic data of an outbreak with polymyxin B (PB)- and carbapenem-resistant Klebsiella pneumoniae during the COVID-19 pandemic. Twenty-six PB- and carbapenem-resistant K. pneumoniae were isolated from patients in the COVID-19 ICU (Intensive Care Unit), non-COVID-19 ICU (Intensive Care Unit), clinical, or surgical ward. Bacterial identification, drug susceptibility tests, and DNA sequencing were performed, followed by in silico resistance genes identification. All isolates showed extensively drug-resistant (XDR) phenotypes. Four different sequence types (ST) were detected: ST16, ST11, ST258, and ST437. Nineteen isolates were responsible for an outbreak in the ICU in September 2020. They belong to ST258 and harbored the 42Kb IncX3plasmid (pKP98M3N42) with the same genomic pattern of two K. pneumoniae identified in 2018. Twenty-four isolates carried bla-KPC-2 gene. No plasmid-mediated colistin (mcr) resistance genes were found. Eight isolates presented mgrB gene mutation. The clonal isolates responsible for the outbreak came from patients submitted to pronation, with high mortality rates in one month. XDR-K. pneumoniae detected during the outbreak presented chromosomal resistance to PB and plasmid-acquired carbapenem resistance due to KPC production in most isolates and 42Kb IncX3(pKP98M3N42) plasmid carrying blaKPC-2 was associated with ST258 isolates. The outbreak followed the collapse of the local healthcare system with high mortality rates.

Efficacy of House Dust Mite Sublingual Immunotherapy in Patients with Atopic Dermatitis: A Randomized, Double-Blind, Placebo-Controlled Trial.

BACKGROUND: Sensitization to house dust mites (HDMs) is frequent in patients with atopic dermatitis. OBJECTIVE: To investigate the efficacy of sublingual immunotherapy (SLIT) with Dermatophagoides pteronyssinus extract in patients with atopic dermatitis sensitized to HDM. METHODS: In this randomized, double-blind, placebo-controlled trial, we enrolled 91 patients 3 years or older, with SCORing Atopic Dermatitis (SCORAD) score greater than or equal to 15 and positive skin test result and/or IgE to D pteronyssinus. Patients were stratified according to age (<12 and ≥12 years) to receive HDM SLIT or placebo for 18 months. Primary outcome was a greater than or equal to 15-point decrease in SCORAD score. Secondary outcomes were decreases in SCORAD and objective SCORAD, Eczema Area and Severity Index, visual analog scale for symptoms, and pruritus scale scores; Investigator's Global Assessment 0/1; and decrease greater than or equal to 4 points in Dermatology Life Quality Index. Background therapy was maintained. RESULTS: A total of 66 patients completed the study (35 HDM SLIT, 31 placebo). After 18 months, 74.2% and 58% of patients in the HDM SLIT group and the placebo group, respectively, showed greater than or equal to 15-point decrease in SCORAD score (relative risk, 1.28; 95% CI, 0.89-1.83). Significant SCORAD score decreases from baseline of 55.6% and 34.5% in HDM SLIT and placebo groups (mean difference, 20.4; 95% CI, 3.89-37.3), significant objective SCORAD score decreases of 56.8% and 34.9% in HDM SLIT and placebo groups (mean difference, 21.3; 95% CI, 0.66-41.81), and more patients with Investigator's Global Assessment 0/1 in the HDM SLIT group as compared with the placebo group (14 of 35 vs 5 of 31; relative risk, 2.63; 95% CI, 1.09-6.39) were observed at 18 months. CONCLUSIONS: Our results suggest that HDM SLIT may be effective in HDM-sensitized patients as an add-on treatment for atopic dermatitis.

HIV-negative pulmonary disease caused by nontuberculous mycobacteria in Southern Brazil: clinical and microbiological characterization.

BACKGROUND: Nontuberculous mycobacteria (NTM) have been identified with increasing frequency in the clinical practice. The aim of this study was to characterize NTM isolates in respiratory specimens from patients with pulmonary disease and to correlate this with clinical/radiological findings, decision to start treatment and outcomes. METHODS: A cross-sectional descriptive study was performed and included all patients who had at least one NTM isolated in respiratory specimens between 2011 and 2014. NTM culture was performed in liquid medium followed by immunochromatographic identification (anti-MPT64). Species identification was based on nucleic acid amplification followed by restriction analysis of a 441 bp fragment of the hsp65 gene (hsp65 PRA) and patients' records were reviewed. RESULTS: From 14,394 cultures in 4 years, 590 (4.10%) grew NTM and 305 (51.7%) isolates were characterized till species level, representing 290 patients including those with and without human immunodeficiency virus (HIV) infection. Two hundred and eleven non-HIV patients had NTM isolated from respiratory specimens, 49 (23.2%) had criteria for active disease based on the American Thoracic Society (ATS) 2007. The majority was men above 51 years old and M. intracellulare was detected in 59.2% (29/49), followed by M. avium 14.3% (7/49), and M. abscessus 12.2% (6/49). CONCLUSIONS: Old age, nodular and nodular/bronchiectasis radiographic pattern, previous tuberculosis (TB) treatment and M. intracellulare were more frequent among NTM-disease patients compared to those only colonized. Positive culture and maintenance of clinical symptoms (poor outcome) was a rule when M. abscessus caused NTM-disease. Positive acid-fast smear in respiratory specimen is a strong predictor of disease.

A predictive score followed by nucleic acid amplification for adult tuberculous meningitis diagnosis in Southern Brazil.

From 2012 to 2013, 300 adults under investigation of tuberculous meningitis (TBM) were tested with polymerase chain reaction (PCR) in central spinal fluid (CSF), followed by TBM score calculation. There were 33(11%) confirmed TBM cases based on clinical findings, CSF-culture; biopsy/necropsy exams and clinical improvement after tuberculosis specific treatment. Other 267 adults were classified as non-TBM. Based on the original score there were 143 possible cases (6≤score≤11) and 20(60.6%) out of 33 TBM; among 27 probable TBM (score≥12) there were 13/33 (39.4%) confirmed cases. The CSF-PCR detected 48% (16/33) of TBM. Based on these findings, a new cut-off point was proposed to differentiate probable (score≥10) from possible (6≤score≤9) TBM. After score adjustment, there were 61 probable TBM with 26/33 (78.8%) TBM, and among the 109 possible TBM there were 7/33(21.2%) confirmed cases. In both systems, there were 130 non-TBM (score≤5) and no confirmed TBM. The association of adjusted score (≥10) and CSF-PCR showed high sensitivity (90.9%) and specificity (86.9%), positive and negative predictive value of 46.2% and 98.9%, respectively. The combination of CSF-PCR and TBM score is a useful tool for the management of adults under investigation of TBM, but the best cut-off point may need local/regional adjustments.