Extensive Drug Resistance Research Articles

The efficacy of drug resistant tuberculosis treatment in patients with different comorbidity status

Introduction. The efficacy of multidrug resistant (MDR) and extensive drug resistance (XDR) tuberculosis (TB) therapy is not yet resolved up to now. New regimens including tioureidoiminomethylpyridinium perchlorate (Tpp) and bedaquiline (Bq) can improve the efficacy of treatment, but due to the growing comorbidities and lack of comprehensive assessment of their severity it is difficult to define the impact of such comorbidities on the efficacy of treatment in this cohort of patients. Ма-terials and methods. Retrospective study has been conducted to review the efficacy of therapy in MDR and XDR TB patients from 18 years of age and with bacteri-al excretion (n=303), who received therapy from 2016 tо 2019. Patients were divided into two main groups: Group I — patients with MDR TB (n=153); Group II — pa-tients XDR TB (n=150). Statistical analysis of the results was carried out via Statistica 10.0 and SPSS 16.0 & Graph-Pad Prism 6 software. Spearman’s correlation coefficient was applied, with meaningful p≤0.05. Results. Theeffi-cacy of therapywas statistically significant higher in MDR TB patients (66.7% vs 40.7%, where χ2=20.6, р<0.01), meanwhile XDR TB patients on the background of low efficacy of treatment show significantly high percent of defaulted treatment (16.7% vs 3.9%, where χ2=13.4, р<0.01). Comorbidity impacts of therapy in XDR TB pa-tients’ treatment especially chronic liver pathology and gastrointestinal diseases (GIT). However, applying Tpp and Bq in scheme of therapy, the treatment outcomes in XDR TB patients with Charlson comorbidity index (ChI) from 3 to 4 improved in 44,8 и 41,1% of cases respec-tively. Conclusions. XDR TB patients are the most severe group of patients in terms of comorbidities that contrib-ute to the low efficacy of treatment. Applying of Tpp and Bq in scheme of therapy allows to efficacy of treatment in 44,8 и 41,1% of cases respectively in severe comorbid-ity patients. It is recommended to use in scheme of ther-apy new anti-TB drugs (Tpp and Bq) after examination of chronic liver pathology and GIT diseases.

Isolation, Characterization andin vitroEvaluation of Specific Bacteriophages Targeting Extensive Drug Resistance Strains ofPseudomonas aeruginosaIsolated from Septic Burn Wounds

BackgroundAntibiotic resistant bacteria and various infections caused by them especially extensive drug resistance (XDR) strains and worrying statistics of mortality due to these strains and also the lack of a clear vision for development and production of new effective antibiotics have made the necessity of using alternative therapies more apparent.Materials and MethodsIn this study, specific phages affecting the Pseudomonas aeruginosa XDR strain were extracted from hospital wastewater and their laboratory characteristics along with lysis effect on 40 XDR strains of P. aeruginosa were investigated.ResultsThe results indicated that three isolated phages (PaB1, PaBa2 and PaBa3) belonged to the Myoviridae and Pododoviridae families and were specific to Pseudomonas aeruginosa strains. More than 98% of phages absorbed their host in less than 10 minutes (Adsorption time <10 min) and completed their lytic cycle after 40 minutes (latent time = 40 min). Burst size of PaBa1, PaBa2 and PaBa3 was 240, 250 and 220 pfu/cell, respectively. PaBa1 lysed 62.5% of the XDR strains with the highest efficiency. The three Phage cocktail was effective against 67.5% of the studied strains.ConclusionThe results of this study indicate the significant potential of these phages for therapeutic use and prophylaxis of infections caused by this bacterium.

ЛЕЧЕНИЕ ТУБЕРКУЛЕЗА ОРГАНОВ ДЫХАНИЯ С МНОЖЕСТВЕННОЙ И ШИРОКОЙ ЛЕКАРСТВЕННОЙ УСТОЙЧИВОСТЬЮ МИКОБАКТЕРИЙ ТУБЕРКУЛЕЗА У ДЕТЕЙ И ПОДРОСТКОВ

The review provides data of literature search for the management of pulmonary TB with multiple or extensive drug resistance. It also represents the analysis of relevant recommendations of the World Health Organization (WHO) and applicable regulatory documents of the Russian Federation on chemotherapy of children and adolescents with drug– resistant TB. Data on the effectiveness of modern approaches to chemotherapy of TB in children and adolescents have been studied based on different types of research

КОГОРТНЫЙ АНАЛИЗ РЕЗУЛЬТАТИВНОСТИ ЛЕЧЕНИЯ БОЛЬНЫХ ТУБЕРКУЛЕЗОМ, В ТОМ ЧИСЛЕ С УСТОЙЧИВОСТЬЮ К РИФАМПИЦИНУ, С МНОЖЕСТВЕННОЙ И ШИРОКОЙ ЛЕКАРСТВЕННОЙ УСТОЙЧИВОСТЬЮ ВОЗБУДИТЕЛЯ К ПРОТИВОТУБЕРКУЛЕЗНЫМ ПРЕПАРАТАМ В РОССИЙСКОЙ ФЕДЕРАЦИИ ЗА 2016–2020 гг.

Objective: to analyze treatment outcomes in patients with TB, including multiple and extensive drug resistant TB (MDR/XDR-TB), in the Russian Federation in 2016–2020. Materials and methods. We used data from the state statistical observation and specialized inquiries. Results. During the five years the treatment success rate decreased from 64.9% in 2016 to 61.4% in 2020 while the proportion of unfavourable outcomes (treatment failure, death, lost for observation) grew from 27.1% in 2016 to 28.0% in 2020. The treatment success rate for chemotherapy regimens 1, 2, and 3 decreased from 69.0% in 2017 to 66.0% in 2020, which produced a negative impact on the indicative rate of treatment success for all TB cases (r = 0.99; p &lt; 0.05). There was persistent growth in the number of cases (15,896 in 2011, 28,336 in 2018) and the treatment success rate for chemotherapy regimens 4 and 5 (MDR-TB cases) (37.1% in 2011, 56.1% in 2017). In 2020 the proportion of favourable outcomes for MDR-TB cases decreased from 56.1% in 2019 to 54.9% due to a growing number of treatment interrupters. During the recent five years we observed a dramatic growth in the number of XDR-TB cases (from 1,318 in 2012 to 4,968 in 2018) and the growing treatment success rate for XDR-TB cases (from 26.1% in 2012 to 42.9% in 2017 and 39.7% in 2018) while the lethality from XDR-TB decreased from 25.3% of cases notified in 2012 to 19.8% of cases notified in 2018. In 2017 and 2018 we observed the growing proportion of treatment failure cases (from 21.0% to 23.9%) and treatment interrupters (from 7.4% to 10.3%). Conclusion. The current dynamics of treatment success rate cannot lead to achieving the goals of the «Stop TB» strategy in the Russian Federation by 2025. The goals might be achieved by increasing effectiveness of treatment of TB patients, which receive chemotherapy regimens 1, 2, and 3. The treatment success rate for chemotherapy regimens 4 and 5 has grown from 54.7% to 56.1% due to decreased lethality from TB or other causes; this was preconditioned by the wide use of modern drugs (bedaquiline), new treatment protocols, and increased implementation of molecular genetic examinations for TB. The proportion of transferred out cases decreased due to the implementation of the Federal register of TB cases and improved access to ultimate treatment outcomes. In 2018 the number of MDR/XDR-TB cases continued to grow predominantly due to newly diagnosed cases. However, the treatment success rate fell due to a growing proportion of treatment interrupters (the typical effect of the COVID-19 pandemic) and increasing lethality from causes other than TB (including deaths from COVID-19). Effectiveness of XDR-TB treatment is slowly growing because of undeveloped infrastructure for testing novel drugs. The proportion of cases lost for the observation increased in the cohort of 2018 due to the COVID-19 pandemic; the general death rate decreased.Keywords: TB, multiple drug resistance, extensive drug resistance, the WHO «Stop TB» strategy, TB treatment, chemotherapy regimens, cohort analysis, deaths from TB.

Molecular Detection of Carbapenemase Genes in Extensive Drug Resistant &amp;lt;i&amp;gt;Acinetobacter baumannii&amp;lt;/i&amp;gt; Clinical Isolates from ICU Patients, Khartoum

Background: The emergence of carbapenemase producing Acinetobacter baumannii is increasingly reported nowadays and constitutes a major problem to the intensive care unit (ICU) patients with notable extensive-drug resistance ability. The study investigates carbapenemase producing A. baumannii strains exhibiting an extensively drug-resistant (XDR) phenotype, isolated from ICU patients in Khartoum. Methods: A total of 100 nonduplicate Gram-negative coccobacilli strains were obtained from microbiology laboratory of ICU patients’ clinical isolates. Molecular identification of A. baumannii was performed by targeting 16S rRNA gene using specifically designed primers. Then, XDR strains were determined by susceptibility testing (disc diffusion). For detection of carbapenemase genes Polymerase chain reaction (PCR) was carried out. Result: Of 100 ICU clinical isolates, 38 (38.0%) was confirmed A. baumannii strains, those strains showed 100% carbapenem resistance and 60.5% extensive drug resistance to the antibiotics tested. The frequency of carbapenemase producer was 57.9% (22/38) of carbapenem resistance A. baumannii (CRAB). The most common carbapenemase associated with resistance was blaOXA gene followed by blaNDM and blaGES A. baumannii isolates. The co-occurrence of blaOXA-48-like and blaNDM, blaOXA-23-like and blaOXA-51, and blaNDM-1 and blaOXA-51 was detected in 22.7%, 18.2% strains and 4.5% respectively. A unique characteristic of our findings was the coharbouring of the genes blaNDM-1, blaOXA-23-like, blaOXA-51 and blaOXA-143 in 9.1% strains (2/22), and this was the first report in the Khartoum city, Sudan. Conclusion: We have demonstrated for the first time a high prevalence of XDR-carbapenemase producing A. baumannii clinical isolates from ICU patients in Khartoum. Also an emergent blaOXA-143 was reported as High-Risk Clones. This highlights the routine mentoring of XDR-carbapenemase producing A. baumannii to avoid clone dissemination in our region hospitals.

Burden of multidrug and extensively drug-resistant ESKAPEE pathogens in a secondary hospital care setting in Greece.

Bacterial antibiotic resistance (AMR) is a significant threat to public health, with the sentinel 'ESKAPEE' pathogens, being of particular concern. A cohort study spanning 5.5 years (2016-2021) was conducted at a provincial general hospital in Crete, Greece, to describe the epidemiology of ESKAPEE-associated bacteraemia regarding levels of AMR and their impact on patient outcomes. In total, 239 bloodstream isolates were examined from 226 patients (0.7% of 32 996 admissions) with a median age of 75 years, 28% of whom had severe comorbidity and 46% with prior stay in ICU. Multidrug resistance (MDR) was lowest for Pseudomonas aeruginosa (30%) and Escherichia coli (33%), and highest among Acinetobacter baumannii (97%); the latter included 8 (22%) with extensive drug-resistance (XDR), half of which were resistant to all antibiotics tested. MDR bacteraemia was more likely to be healthcare-associated than community-onset (RR 1.67, 95% CI 1.04-2.65). Inpatient mortality was 22%, 35% and 63% for non-MDR, MDR and XDR episodes, respectively (P = 0.004). Competing risks survival analysis revealed increasing mortality linked to longer hospitalisation with increasing AMR levels, as well as differential pathogen-specific effects. A. baumannii bacteraemia was the most fatal (14-day death hazard ratio 3.39, 95% CI 1.74-6.63). Differences in microbiology, AMR profile and associated mortality compared to national and international data emphasise the importance of similar investigations of local epidemiology.

Emergence of dual and multicarbapenemase coproducing organisms in the United States.

Carbapenemase-producing organisms commonly carry a single carbapenemase gene conferring resistant to carbapenems and other β-lactam antibiotics. Here, we report rare cases of multidrug-resistant Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii strains that coproduce multiple carbapenemases and exhibit extensive drug resistance. Such resistant strains are rarely identified in the United States.

Molecular Characterization of ESBLs and QnrS Producers From Selected Enterobacteriaceae Strains Isolated From Commercial Poultry Production Systems in Kiambu County, Kenya.

Background:The emergence and spread of Extended-spectrum β-lactamases (ESBLs) in Enterobacteriaceae through the plasmid-mediated exchange have become a major threat to public health by complicating the treatment of severe infections in both animals and humans. Therefore, the current study focused on evaluating the manifestation of ESBLs production from the fecal isolates of E. coli, Shigella spp, Salmonella spp, and Klebsiella spps in commercial poultry production systems of Kiambu County, Kenya.Materials and methods:Out of 591 isolates identified as E. coli, Shigella spp, Salmonella spp, and Klebsiella spps from 437 fecal samples, only 78 were phenotypically suggestive to be ESBL producers. The possible ESBL producers were screened for the presence of blaTEM, blaCTX-M, blaOXA, and blaSHV using the PCR technique. These isolates were also screened for carriage of the QnrS gene that confers resistance to the fluoroquinolone class of drugs.Results:The most detected ESBL gene from the isolates was blaOXA (n = 20; 26%), followed by blaTEM (n = 16, 21%), with the majority of them detected in E. coli. The blaCTX-M was identified in all the 4 enteric’s bacteria-type isolates tested. Three E. coli and Salmonella spp respectively were found to harbor all the 5 antimicrobial resistance (AMR) gene types. The blaTEM, blaOXA, blaSHV, and QnrS genes were not detected from Klebsiella and Shigella spps. Additionally, most of the AMR gene co-carriage was detected in both E. coli and Salmonella spps as follows blaTEM + blaOXA (n = 4); blaTEM + QnrS (n = 3); blaTEM + blaOXA + QnrS (n = 3), concurrently.Conclusion:Our findings highlight the significance of commercial poultry production in disseminating transferable antibiotic resistance genes that act as potential sources of extensive drug resistance in livestock, humans, and the environment, leaving limited therapeutic options in infection management.

Pathology of pulmonary tuberculosis: has the tiger changed it's stripes?

:BackgroundIndia accounts for the highest number of TB cases globally (almost one-fifth of the global burden and almost two-thirds of the cases in South East Asia. Furthermore, the development of drug resistance of varying levels such as multi-drug resistant TB (MDR-TB), extensively-drug resistance TB (XDR-TB) and total-drug resistant TB (TDR-TB) has been on the increase, and now India also features in the 27 high-MDRTB-burden countries. Almost parallel to these developments, in the last few years, we have been encountering less common morphological forms of pulmonary TB (PTB) at autopsies. With these less common manifestations of the disease, we undertook this study to examine the changing trends in the morphological pattern of pulmonary TB over the recent years.MethodsIn this 3-year retrospective study, adult autopsy cases of PTB (that significantly contributed to the final cause of death) were studied in detail. HIV-positive cases were excluded from the study. The clinical details, gross appearances of the pulmonary lesions, microscopic pattern and Ziehl-Neelsen (ZN) staining were studied. Extrapulmonary involvement and causes of death were documented.ResultsPulmonary tuberculosis as a cause of death at autopsy was seen in 130 adult patients over 3 years. The age range was between 12 to 70 years. Anti-tuberculous therapy had been administered in 33 of them, but only one patient had taken complete therapy. Dyspnea was the commonest respiratory symptom seen in 51 cases (39.2%). Tuberculous bronchopneumonia was the commonest lesion (45.3%), miliary lesions (including localized miliary) accounted for 26% while fibrocavitary lesions (including the ones not involving apex) were seen in 13% cases. Other morphologies included nodular forms of TB (13%), localized miliary lesions (11.9%), and fibrocavitary lesions, not necessarily involving the apex (11.7% of all fibrocavitary cases), and predominant pleuritis with underlying lung involvement by TB in 1 case. Many cases of TB bronchopneumonia had a bronchocentric pattern of distribution (14.7%). On microscopy, caseating granulomas were seen in 93% cases, only caseation necrosis was seen in 4.6% cases, and necrotizing granulomas with abscess-like reaction in 11.5% cases. ZN staining was positive in 92 cases (70.7%). All the extrapulmonary lesions showed caseating granulomas histologically. The final cause of death was found to be primarily tuberculous in 106 cases (81.5%), whereas in 24 cases (19.5%) pulmonary TB was attributed to the secondary cause of death.ConclusionThe typical apical involvement of secondary TB was not seen in most of our cases. This could indicate a difference in the morphology and the pattern of lung involvement in recent years. The difference in gross morphology does not affect the pattern of involvement of the lung. In our study, we have observed both; a change in morphology, i.e., more cases of TB bronchopneumonia, and a change in the pattern of involvement like nodular forms, localized miliary forms, and fibrocavitary lesions not necessarily involving the apex. We postulate that this less common manifestation of pulmonary TB is closely related to the development of multi-drug and microbial resistance posing serious medical challenges.

A retrospective analytical study of treatment outcomes among multi drug resistant tuberculosis patients

Background: India is amongst one of the high multidrug resistant tuberculosis (MDR-TB) burden countries globally with a huge contribution given by the state of Uttar Pradesh. Programmatic Management of Drug Resistant Tuberculosis, initiated in 2007 has taken over the disorganized and unsupervised treatment practice in India. However, regular scrutiny is required which points out both its success and failure. Aim &amp; Objective: This study was conducted to evaluate final treatment outcomes among MDR-TB patients on standard Category IV regimen Settings and Design: Retrospective analysis was done using secondary data from medical records of all patients. Methods and Material: Data of all MDR-TB patients registered under RNTCP at King George’s Medical University, Lucknow from 2013 to 2016 was collected. Demographic details along with pre-defined treatment outcomes were recorded (cured, treatment completed, death, treatment failure, treatment default and transfer to higher centre). Statistical analysis used: Descriptive statistics using numbers and percentage. Results: The records of 3580 MDR tuberculosis patients registered at drug resistant tuberculosis centre in King George’s Medical University from January 2013 to December 2016 were included which consisted of 67%males and 33%female. Mean age of presentation was 31.17 years (95% CI 30.75-31.59). Mean weight of patients was 40.16 kg (95% CI 39.89-40.43). Year wise distribution of registered cases from 2013 to 2016 was 611, 799, 984 and 1186 patients respectively. Amongst 3580 patients, 30.39% were declared cured, 25.50% completed treatment, 21.39% died, 0.84% showed treatment failure, 12.54% were defaulters, 2.35% were transferred out to higher centre, 6.5% were shifted to regimen for Extensive drug resistant (EDR) TB, 0.16% patients needed to stop treatment due to ADR and 0.33% patient were still on treatment. Conclusion: The treatment success rate of MDR?TB patients is still low. Measures to improve treatment adherence as in National tuberculosis elimination programme (NTEP) attempts to further improve the success rate.

GENOMIC ANALYSIS OF LAM FAMILY OF MYCOBACTERIUM TUBERCULOSIS CLINICAL STRAINS

Drug-resistant tuberculosis is a global problem for humanity, especially in the countries of Southeast Asia, Eastern Europe and the CIS. In Kazakhstan, the rate of drug-resistant tuberculosis among newly diagnosed patients is more than 20%. Moreover, the Republic of Kazakhstan ranks second among the thirty countries with a high disease burden according to the World Health Organization. In this regard, it becomes obvious that it is necessary to study the nature of resistance of locally circulating strains of mycobacteria. The use of genetic typing methods will allow tracking the spread of tuberculosis pathogens of any family, which, in turn, will provide a personalized approach to treatment. The strains of the Mycobacterium tuberculosis complex capable of infecting humans include seven phylogenetic lineages, initially associated with their geographical distribution. In this study, the genomes of three drug-resistant clinical isolates of the Latin American Mediterranean family (LAM) circulating in Kazakhstan were studied. We used whole genome sequencing to study the distribution and drug resistance of isolates. Phylogenetic analysis grouped the genomes described in this study with sequences from Russia, Uzbekistan and Kazakhstan, also belonging to the LAM family. One isolate was identified as having extensive drug resistance to seven anti-TB drugs. Our results suggest that at least two drug-resistant genotypes of the LAM family are circulating in Kazakhstan. Thus, the use of genetic methods is becoming more and more popular and effective in combating the spread of tuberculosis infection.

National trends in hospital, long-term care and outpatient Acinetobacter baumannii resistance rates.

Introduction. Acinetobacter baumannii is a top-priority pathogen of the World Health Organization (WHO) and the Centers for Disease Control (CDC) due to antibiotic resistance.Gap Statement. Trends in A. baumannii resistance rates that include community isolates are unknown.Aim. Identify trends in A. baumannii resistance rates across the Veterans Affairs (VA) Healthcare System, including isolates from patients treated in hospitals, long-term care facilities and outpatient clinics nationally.Methodology. We included A. baumannii clinical cultures collected from VA patients from 2010 to 2018. Cultures were categorized by location: VA medical centers (VAMCs), long-term care (LTC) units [community living centers (CLCs)], or outpatient. We assessed carbapenem resistance, multidrug resistance (MDR) and extensive drug resistance (XDR). Time trends were assessed with Joinpoint regression.Results. We identified 19 376 A. baumannii cultures (53% VAMCs, 4% CLCs, 43% outpatient). Respiratory cultures were the most common source of carbapenem-resistant (43 %), multidrug-resistant (49 %) and extensively drug-resistant (21 %) isolates. Over the study period, the number of A. baumannii cultures decreased significantly in VAMCs (11.9% per year). In 2018, carbapenem resistance was seen in 28% of VAMC isolates and 36% of CLC isolates, but only 6% of outpatient isolates, while MDR was found in 31% of VAMC isolates and 36% of CLC isolates, but only 8 % of outpatient isolates. Carbapenem-resistant, multidrug-resistant and extensively drug-resistant A. baumannii isolates decreased significantly in VAMCs and outpatient clinics over time (VAMCs: by 4.9, 7.2 and 6.9%; outpatient: by 11.3, 10.5 and 10.2% per year). Resistant phenotypes remained stable in CLCs.Conclusion. In the VA nationally, the prevalence of A. baumannii is decreasing, as is resistance. Carbapenem-resistant and multidrug-resistant A. baumannii remain common in VAMCs and CLCs. The focus of infection control and antimicrobial stewardship efforts to prevent transmission of resistant A. baumannii should be in hospital and LTC settings.

Whole-Genome Sequencing of Gram-Negative Bacteria Isolated From Bovine Mastitis and Raw Milk: The First Emergence of Colistin mcr-10 and Fosfomycin fosA5 Resistance Genes in Klebsiella pneumoniae in Middle East.

Antimicrobial resistance is a major concern in the dairy industry. This study investigated the prevalence, antimicrobial resistance phenotypes, and genome sequencing of Gram-negative bacteria isolated from clinical (n = 350) and subclinical (n = 95) bovine mastitis, and raw unpasteurized milk (n = 125). Klebsiella pneumoniae, Aeromonas hydrophila, Enterobacter cloacae (100% each), Escherichia coli (87.78%), and Proteus mirabilis (69.7%) were the most prevalent multidrug-resistant (MDR) species. Extensive drug-resistance (XDR) phenotype was found in P. mirabilis (30.30%) and E. coli (3.33%) isolates. Ten isolates (four E. coli, three Klebsiella species and three P. mirabilis) that displayed the highest multiple antibiotic resistance (MAR) indices (0.54–0.83), were exposed to whole-genome sequencing (WGS). Two multilocus sequence types (MLST): ST2165 and ST7624 were identified among the sequenced E. coli isolates. Three E. coli isolates (two from clinical mastitis and one from raw milk) belonging to ST2165 showed similar profile of plasmid replicon types: IncFIA, IncFIB, IncFII, and IncQ1 with an exception to an isolate that contained IncR, whereas E. coli ST7624 showed a different plasmid profile including IncHI2, IncHI2A, IncI1α, and IncFII replicon types. ResFinder findings revealed the presence of plasmid-mediated colistin mcr-10 and fosfomycin fosA5 resistance genes in a K. pneumoniae (K1) isolate from bovine milk. Sequence analysis of the reconstructed mcr-10 plasmid from WGS of K1 isolate, showed that mcr-10 gene was bracketed by xerC and insertion sequence IS26 on an IncFIB plasmid. Phylogenetic analysis revealed that K1 isolate existed in a clade including mcr-10-harboring isolates from human and environment with different STs and countries [United Kingdom (ST788), Australia (ST323), Malawi (ST2144), Myanmar (ST705), and Laos (ST2355)]. This study reports the first emergence of K. pneumoniae co-harboring mcr-10 and fosA5 genes from bovine milk in the Middle East, which constitutes a public health threat and heralds the penetration of the last-resort antibiotics. Hence, prudent use of antibiotics in both humans and animals and antimicrobial surveillance plans are urgently required.

Whole-genome sequencing-based phylogeny, antibiotic resistance, and invasive phenotype of Escherichia coli strains colonizing the cervix of women in preterm labor

BackgroundEscherichia coli is a major neonatal pathogen and the leading cause of early-onset sepsis in preterm newborns. Maternal E. coli strains are transmitted to the newborn causing invasive neonatal disease. However, there is a lack of data regarding the phenotypic and genotypic characterization of E. coli strains colonizing pregnant women during labor.MethodsThis prospective study performed at the University of Oklahoma Medical Center (OUHSC) from March 2014 to December 2015, aimed to investigate the colonization rate, and the phylogeny, antibiotic resistance traits, and invasive properties of E. coli strains colonizing the cervix of fifty pregnant women diagnosed with preterm labor (PTL). Molecular analyses including bacterial whole-genome sequencing (WGS), were performed to examine phylogenetic relationships among the colonizing strains and compare them with WGS data of representative invasive neonatal E. coli isolates. Phenotypic and genotypic antibiotic resistance traits were investigated. The bacteria’s ability to invade epithelial cells in vitro was determined.ResultsWe recruited fifty women in PTL. Cervical samples yielded E. coli in 12 % (n=6). The mean gestational age was 32.5 (SD±3.19) weeks. None delivered an infant with E. coli disease. Phenotypic and genotypic antibiotic resistance testing did not overall demonstrate extensive drug resistance traits among the cervical E. coli isolates, however, one isolate was multi-drug resistant. The isolates belonged to five different phylogroups, and WGS analyses assigned each to individual multi-locus sequence types. Single nucleotide polymorphism-based comparisons of cervical E. coli strains with six representative neonatal E. coli bacteremia isolates demonstrated that only half of the cervical E. coli isolates were phylogenetically related to these neonatal invasive strains. Moreover, WGS comparisons showed that each cervical E. coli isolate had distinct genomic regions that were not shared with neonatal E. coli isolates. Cervical and neonatal E. coli isolates that were most closely related at the phylogenetic level had similar invasion capacity into intestinal epithelial cells. In contrast, phylogenetically dissimilar cervical E. coli strains were the least invasive among all isolates.Conclusions This pilot study showed that a minority of women in PTL were colonized in the cervix with E. coli, and colonizing strains were not phylogenetically uniformly representative of E. coli strains that commonly cause invasive disease in newborns. Larger studies are needed to determine the molecular characteristics of E. coli strains colonizing pregnant women associated with an increased risk of neonatal septicemia.

A Clinical Case of Extensive Drug Resistant Pulmonary Tuberculosis Using an Endobronchial Valve. Analysis of Errors in the Choice of Chemotherapy Regimen

The article describes a clinical case of a female patient with respiratory tuberculosis exposed to several cases of extensive drug resistance in their family. Tuberculosis progressed in this patient due to the late initiation of adequate treatment. Therefore, the total duration of chemotherapy made 5 years till cure was achieved and an endobronchial valve was used to heal persisting (for 3 years) lung destruction.

Predictors of Drug-Resistant Tuberculosis among High-Risk Population Diagnosed under National Program Conditions in the Littoral Region, Cameroon.

Multiple drug resistance TB (MDR-TB) has greatly jeopardized the effective control of tuberculosis in Africa. This study is aimed at determining the incidence and predictors of drug resistant-TB amongst bacteriologically diagnosed cases in the Littoral region of Cameroon. This was a descriptive cross-sectional survey conducted from January 2016 to December 2017. A total of 1665 participants were enrolled from 32 diagnostic and treatment centers (DTCs) in the Littoral region. Demographic, clinical, socioeconomic, and behavioral data were obtained using a pretested structured questionnaire. Drug susceptibility testing was performed using Gene Xpert MTB/RIF assay and line probe assay (LPA). Consent was obtained from participant/guidance. Data analysis was carried with SPSS version 21. Univariate and multiple logistic regression was performed at 5% significance level. The incidence of rifampicin and MDR-TB was 86 (5.2%) and 75 (4.5%), respectively. More (11.3%) cases of drug resistance were diagnosed in 2016 compared to 2017 (3.7%). Eleven (0.7%) were resistant to rifampicin only. A total of 19 (4.4%) cases of rifampicin resistance were detected from newly diagnosed cases and 67 (5.4%) from previously retreated cases. Pre-XDR-TB was detected in 2 (2.7%) of the MDR-TB cases amongst whom 1 (1.3%) was extensive drug resistance TB (XDR-TB). Age greater than 60 years old (OR = 4.98, p = 0.047), being married (OR = 1.91, p = 0.006), being currently incarcerated (OR = 1.74, p = 0.027), and having contact with known TB cases (OR = 1.88, p = 0.007) were associated to MDR-TB in a univariate analysis. This study highlights the declining rates of TB drug resistance in the region over the years probably due to the introduction of Gene Xpert that results in early detection of RR-TB. It also shows that age greater than 60 years, being married, and incarcerated are predictors of drug resistant-TB, while the year of patient enrolment and previous exposure to TB treatment were independent predictors of drug resistance in the Littoral region of Cameroon.

Genomic Characterization of a Proteus sp. Strain of Animal Origin Co-Carrying blaNDM-1 and lnu(G).

The emergence of carbapenem-resistant Proteus represents a serious threat to global public health due to limited antibiotic treatment options. Here, we characterize a Proteus isolate NMG38-2 of swine origin that exhibits extensive drug resistance, including carbapenems. Whole-genome sequencing based on Illumina and MinION platforms showed that NMG38-2 contains 24 acquired antibiotic resistance genes and three plasmids, among which, pNDM_NMG38-2, a pPvSC3-like plasmid, is transferable and co-carries blaNDM-1 and lnu(G). Sequence analysis of pPvSC3-like plasmids showed that they share a conserved backbone but have a diverse accessory module with complex chimera structures bearing abundant resistance genes, which are facilitated by transposons and/or homologous recombination. The acquisition of blaNDM-1 in pNDM_NMG38-2 was due to the ISCR1-mediated integration event. Comprehensive analysis of the lnu(G)-bearing cassettes carried by bacterial plasmids or chromosomes revealed a diversification of its genetic contexts, with Tn6260 and ISPst2 elements being the leading contributors to the dissemination of lnu(G) in Enterococcus and Enterobacteriaceae, respectively. In conclusion, this study provides a better understanding of the genetic features of pPvSC3-like plasmids, which represent a novel plasmid group as a vehicle mediating the dissemination of blaNDM-1 among bacteria species. Moreover, our results highlight the central roles of Tn6260 and ISPst2 in the spread of lnu(G).

Deep sequencing of HIV-1 reveals extensive subtype variation and drug resistance after failure of first-line antiretroviral regimens in Nigeria.

BackgroundDeep sequencing could improve understanding of HIV treatment failure and viral population dynamics. However, this tool is often inaccessible in low- and middle-income countries.ObjectivesTo determine the genetic patterns of resistance emerging in West African HIV-1 subtypes during first-line virological failure, and the implications for future antiretroviral options.Patients and methodsParticipants were selected from a Nigerian cohort of people living with HIV who had failed first-line ART and subsequently switched to second-line therapy. Whole HIV-1 genome sequences were generated from first-line virological failure samples with Illumina MiSeq. Mutations detected at ≥2% frequency were analysed and compared by subtype.ResultsHIV-1 sequences were obtained from 101 participants (65% female, median age 30 years, median 32.9 months of nevirapine- or efavirenz-based ART). Thymidine analogue mutations (TAMs) were detected in 61%, other core NRTI mutations in 92% and NNRTI mutations in 99%. Minority variants (<20% frequency) comprised 18% of all mutations. K65R was more prevalent in CRF02_AG than G subtypes (33% versus 7%; P = 0.002), and ≥3 TAMs were more common in G than CRF02_AG (52% versus 24%; P = 0.004). Subtype G viruses also contained more RT cleavage site mutations. Cross-resistance to at least one of the newer NNRTIs, doravirine, etravirine or rilpivirine, was predicted in 81% of participants.ConclusionsExtensive drug resistance had accumulated in people with West African HIV-1 subtypes, prior to second-line ART. Deep sequencing significantly increased the detection of resistance-associated mutations. Caution should be used if considering newer-generation NNRTI agents in this setting.

Characteristics of Carbapenem-Resistant Gram-Negative Bacilli in Patients with Ventilator-Associated Pneumonia.

Carbapenem-resistant Gram-negative bacilli (CR-GNB) has become a global threat. In hospital settings, the association of CR-GNB with ventilator-associated pneumonia (VAP) is a critical public health concern owing to their high resistance rate to most antibiotics. The present study aims to identify the frequency of carbapenem-resistance and to determine the rate of multidrug resistance (MDR), extensive drug resistance (XDR) and pan-drug resistance (PDR) among CR-GNB infections in VAP. Antimicrobial susceptibility testing was carried out using the disk diffusion method and the detection of carbapenemases was screened using the imipenem-E test and the modified carbapenem-inactivation method (mCIM). The isolates were verified by polymerase chain reaction (PCR) for the presence of blaNDM, blaSPM, blaVIM, blaIMP and blaGIM genes. 89.5%, 14%, 17.5%, 10.5%, 3.5% of isolates exhibited the presence of blaNDM, blaVIM, blaSPM, blaIMP and blaGIM, respectively. 76%, 17% and 7% of isolates were PDR, XDR, and MDR, respectively. Carbapenem-resistance genes were identified in a significant percentage and blaNDM was the most predominant gene. All isolates were highly resistant to most antibiotics. This health concern has proven to be a big challenge in developing countries such as Egypt, as it is associated with high morbidity, high mortality, and raised healthcare costs.

THE EFFECT OF A TOPICAL AGENT WITH MUPIROCIN ON MULTIDRUG-RESISTANT CLINICAL STRAINS OF S. AUREUS ISOLATED FROM PATIENTS WITH COMMON DERMATOSES

Introduction. Therapy of infectious lesions is complicated due to the growing resistance of the main pathogens of pyoderma, especially S. aureus. A key component of the treatment of diseases with mild and moderate severity is the use of local antistaphylococcal drugs that can reach maximum doses in the focus of secondary infection, minimizing the side effects of antibiotics. The aim is to evaluate the antibacterial activity of the ointment with mupirocin in relation to polyresistant clinical strains of S. aureus, isolated from patients with common dermatoses. Materials &amp; Methods. Using the disk-diffusion method, the antibiotic resistance profile of 142 clinical strains of S. aureus was studied with the revision of the biofilming ability of 36 clinical strains of S. aureus using the method of adhesion to polystyrene. It was evaluated the therapeutic efficacy of the ointment with mupirocin in the treatment of these diseases aggravated by secondary infection. Results. According to the monitoring, the share of multi drug resistance strains (multi drug resistance, MDR) was 54.2 %, and extensive drug resistance (extreme drug resistance, XDR) – 4.9 %. Exactly 49 clinical MDR strains were selected for detailed determination of the antibacterial action of mupirocin. It was found that mupirocin actively suppressed the growth of both MRSA and MSSA. No clinical strain resistant to mupirocin was detected. It was found that 20.0% of clinical strains had a high ability to biofilm formation, medium - 60.0%, low - 20.0%. The ointment with mupirocin exhibits a highly effective antibacterial effect against clinical MRSA. As a result of the use of an ointment with mupirocin for external treatment of patients with common dermatoses during an exacerbation, regression of clinical signs of pyococcal infection was noted in 93.0 % of individuals. Conclusion. As a result of the performed researches it is proved that Mupirocin has rather expressed antistaphylococcal activity, including against MRSA of strains with high ability to formation of biofilms. The level of antimicrobial action of Mupirocin allows to recommend its use as a drug for external therapy of microbial complications of common dermatoses, which will increase the effectiveness of therapy during exacerbation, avoid side effects, reduce systemic pharmacological load, achieve sustainable, long-term remission of the patients. Keywords: clinical strains of S. aureus, antibiotic resistance, external antibiotic therapy, mupirocin.