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1.
Chem Biol Interact ; 333: 109318, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33186599

RESUMO

Antimicrobial resistance is at increasing risk worldwide since it is threatening the ability to control common infectious diseases, resulting in prolonged illness, disability, and death. Herein, we inspired by the effective plant phytochemical mechanisms evolved to overcome microbial pathogenesis and evolved resistance. Cuminaldehyde is previously reported as the main antibacterial component in Calligonum comosum essential oil. The toxicity of cuminaldehyde limits its medical application for human use. On the other hand, compared to cuminaldehyde, the plant total extract showed similar antibacterial activities, while maintained lower toxicity, although it contains 22 times less cuminaldehyde. Thus, we assumed that other components in the plant extracts specifically affect bacteria but not mammalian cells. Bioassay-guided fractionations combined with comparative metabolomics analysis of different plant extracts were employed. The results revealed the presence of bacterial species-specific phytochemicals. Cinnamyl linoleate and linoleic acid enhanced the antibacterial activities of cuminaldehyde and ampicillin against S. aureus including MRSA, while decanal and cinnamyl linoleate enhanced the activities against E. coli. Computational modeling and enzyme inhibition assays indicated that cinnamyl linoleate selectively bind to bacterial ribosomal RNA methyltransferase, an important enzyme involved in the virulence and resistance of multidrug resistant bacteria. The results obtained can be employed for the future preparation of pharmaceutical formula containing cinnamyl linoleate in order to overcome evolved multidrug resistance behaviors by microbes.


Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Caryophyllales/química , Desenho de Fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Óleos Voláteis/química , Compostos Fitoquímicos/química , Antibacterianos/química , Materiais Biomiméticos/síntese química , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Linhagem Celular , Técnicas de Química Sintética , Resistência a Múltiplos Medicamentos/efeitos dos fármacos , Humanos
2.
Int J Food Microbiol ; 337: 108956, 2021 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-33189985

RESUMO

There has been an increase in the number of reports on Salmonella enterica subsp. enterica serovar Infantis (S. Infantis) isolated from animals and humans. Recent studies using whole genome sequencing (WGS) have provided evidence on the likely contribution of a unique conjugative megaplasmid (pESI; ~280 kb) to the dissemination of this serovar worldwide. In the present study, twenty-two unrelated Salmonella strains [S. Infantis (n = 20) and Salmonella 6,7:r:- (n = 2)] and their plasmids were investigated using next generation sequencing technologies (MiSeq and MinION) to unravel the significant expansion of this bacteria in Turkey. Multi-locus sequence typing, plasmid replicons, resistance gene contents as well as phylogenetic relations between strains were determined. According to the WGS data, all S. Infantis possessed the relevant megaplasmid backbone genes and belonged to sequence type 32 (ST32) with the exception of a single novel ST7091. Tetracycline and trimethoprim/sulfamethoxazole resistance were found to be widespread in S. Infantis strains and the resistant strains exclusively carried the tetA, sul1, sul2 and dfrA14 genes. One S. Infantis isolate was also a carrier of the plasmid-mediated ampC via blaCMY-2, gene. Moreover, full genomes of four S. Infantis isolates were reconstructed based on hybrid assembly. All four strains contained large plasmids (240-290 kb) similar to previously published megaplasmid (pESI) and accompanied by several small plasmids. The megaplasmid backbone contained a toxin-antitoxin system, two virulence cassettes and segments associated with heavy metals resistance, while variable regions possessed several antibiotic resistance genes flanked by mobile elements. This study indicated that pESI-like megaplasmid is widely disseminated within the tested S. Infantis strains of chicken meat, warranting further genomic studies on clinical strains from humans and animals to uncover the overall emergence and spread of this serovar.


Assuntos
Genoma Bacteriano/genética , Plasmídeos/genética , Aves Domésticas/microbiologia , Salmonelose Animal/microbiologia , Salmonella/genética , Animais , Antibacterianos/farmacologia , Galinhas/microbiologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Microbiologia de Alimentos , Filogenia , Plasmídeos/efeitos dos fármacos , Salmonella/efeitos dos fármacos , Salmonella/isolamento & purificação , Salmonella/patogenicidade , Salmonelose Animal/epidemiologia , Turquia/epidemiologia , Virulência/genética
3.
Can J Microbiol ; 67(1): 37-52, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32805182

RESUMO

Antimicrobial resistance was evaluated in Campylobacter jejuni isolated from 1291 diarrheic people over a 15-year period (2004-2018) in southwestern Alberta, a model location in Canada with a high rate of campylobacteriosis. The prevalence of resistance to chloramphenicol, clindamycin, erythromycin, and gentamicin was low during the examination period (≤4.8%). Resistance to tetracycline remained consistently high (41.6%-65.1%), and resistance was primarily conferred by plasmid-borne tetO (96.2%). Resistance rates to ciprofloxacin and nalidixic acid increased substantially over the examination period, with a maximal fluoroquinolone resistance (FQR) prevalence of 28.9% in 2016. The majority of C. jejuni isolates resistant to ciprofloxacin (93.9%) contained a C257T single nucleotide polymorphism within the gyrA chromosomal gene. Follow up with infected people indicated that the observed increase in FQR was primarily due to domestically acquired infections. Moreover, the majority of FQ-resistant C. jejuni subtypes (82.6%) were endemic in Canada, primarily linked to cattle and chicken reservoirs; 18.4% of FQ-resistant isolates were assigned to three subtypes, predominantly associated with cattle. Study findings indicate the need to prioritize FQR monitoring in C. jejuni infections in Canada and to elucidate the dynamics of the emergence and transmission of resistant C. jejuni strains within and from cattle and chicken reservoirs.


Assuntos
Antibacterianos/farmacologia , Infecções por Campylobacter/microbiologia , Campylobacter jejuni/isolamento & purificação , Farmacorresistência Bacteriana , Fluoroquinolonas/farmacologia , Alberta/epidemiologia , Animais , Infecções por Campylobacter/epidemiologia , Campylobacter jejuni/classificação , Campylobacter jejuni/efeitos dos fármacos , Campylobacter jejuni/genética , Bovinos , Galinhas , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Humanos , Testes de Sensibilidade Microbiana
4.
J Appl Microbiol ; 130(1): 247-257, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32364269

RESUMO

AIMS: The aim of this study was to report on the occurrence of antimicrobial resistant (AMR) Escherichia coli from retail chicken meat samples in the UK, with particular focus on AmpC and extended spectrum beta-lactamase (ESBL) production and carbapenem resistance. METHODS AND RESULTS: Methods from EU protocols were used for selective isolation of AmpC-/ESBL-producing E. coli, carbapenem-resistant E. coli and for performing minimum inhibitory concentrations. Additional work not part of EU protocols included viable counts, detection by PCR of blaCTX-M , blaOXA, blaSHV and blaTEM genes in ESBL-phenotype E. coli and screening for mcr plasmid-mediated colistin resistance. From the 313/309 retail chicken meat samples tested in 2016/2018, carbapenem or mcr plasmid-mediated colistin-resistant E. coli were not detected. For 2016/2018 chicken samples, 141/42 (45·0%/13·6%), 90/23 (28·8%/7·4%), 48/16 (15·3%/5·2%) and 3/3 (1·0%/1·0%) were positive for ESBL- and/or AmpC-, ESBL- alone AmpC- alone and AmpC+ESBL-phenotype E. coli respectively. ESBL-producing E. coli were predominantly blaCTX-M-1 . All AmpC and/or ESBL-phenotype E. coli were sensitive to colistin, ertapenem, imipenem, meropenem, temocillin and tigecycline, applying epidemiological cut-off values. CONCLUSIONS: A previous study in 2013/14 showed that 65·4% of retail chicken meat samples tested in the UK were positive for ESBL-producing (mainly CTX-M) E. coli. Since then the proportion of samples positive in the UK has dropped significantly to 7·4% in 2018. SIGNIFICANCE AND IMPACT OF THE STUDY: Significant reductions in antimicrobials used in the UK poultry meat sector between 2012 and 2016 may be linked to significant reductions in AmpC/ESBL-phenotype E. coli in retail chicken between 2013/14 and 2018.


Assuntos
Farmacorresistência Bacteriana , Escherichia coli/isolamento & purificação , Aves Domésticas/microbiologia , beta-Lactamases/metabolismo , Animais , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Galinhas , Colistina/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Escherichia coli/efeitos dos fármacos , Escherichia coli/enzimologia , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/veterinária , Microbiologia de Alimentos , Testes de Sensibilidade Microbiana , Plasmídeos/genética , Plasmídeos/metabolismo , Reino Unido/epidemiologia , beta-Lactamases/genética
5.
BMC Infect Dis ; 20(1): 936, 2020 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-33297983

RESUMO

BACKGROUND: In spite of the evident general negative effects of armed conflict on countries' health systems and populations' health outcomes, little is known about similar impacts of conflicts on the spread of antimicrobial resistances (AMR). This review was to address this evidence gap and describe: 1. Patterns of AMR in the Middle East (ME) and resistance profiles of pathogens included in the Global AMR Surveillance System (GLASS) supported by the World Health Organization; 2. Differences in proportions of AMR isolates between conflict and non-conflict countries. METHODS: A systematic literature review was conducted following PRISMA guidelines and searching five electronic databases. Subject heading and free text were searched for "antimicrobial resistances" and "Middle East", to identify observational studies on AMR published from January 2011 to June 2018. Data were extracted from included articles on a predefined set of variables. Percentages of AMR were analysed as median and interquartile ranges. Risk of bias was assessed using the Newcastle-Ottawa Scale. RESULTS: A total of 132 articles met the inclusion criteria. Included studies showed heterogeneity in study design, laboratory methods and standards for interpretation of results, and an overall high risk of bias. Main findings were the following: 1. High proportions of carbapenem resistance in Acinetobacter spp. (median 74.2%), and both carbapenem resistance (median 8.1 and 15.4% for E. coli and K. pneumoniae respectively) and ESBL-production (median 32.3 and 27.9% for E. coli and K. pneumoniae respectively) amongst Enterobacteriaceae. S. aureus isolates showed a median methicillin resistance percentage of 45.1%, while vancomycin resistance was almost absent. A median of 50% of the strains of S. pneumoniae showed non-susceptibility to penicillin. 2. Similar trends were observed in conflict and non-conflict affected countries. CONCLUSIONS: There is a lack of standardization in the methodological approach to AMR research in the Middle East. The proportion of antibiotic resistances among specific GLASS pathogens is high, particularly among Acinetobacter spp.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Klebsiella pneumoniae/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Penicilinas/farmacologia , Humanos , Testes de Sensibilidade Microbiana , Oriente Médio , Vigilância em Saúde Pública
6.
BMC Infect Dis ; 20(1): 944, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33302900

RESUMO

BACKGROUND: Mycobacterium abscessus is a rapidly growing mycobacteria involved in severe infections of the lung, skin, or soft tissue. Macrolides such as clarithromycin are the recommended first line drugs for treatment of M. abscessus infections. However, M. abscessus has dual mechanisms of resistance to macrolides, making treatment by macrolides difficult. A functional erm(41) gene confers for inducible resistance while acquired mutations on the 23S rRNA rrl gene confer for constitutive resistance. METHODS: We have developed a real-time PCR assay to detect both inducible and acquired resistance to clarithromycin, and compared the results to traditional erm(41) and rrl sequencing and phenotypic susceptibility testing using Sensititre™ plates. RESULTS: Of the total 126 M. abscessus isolates tested, truncated erm(41) was found in 23/126 (18.3%) of the samples, 27/126 (21.4%) had a T28C mutation in erm(41), and 2/126 (1.6%) had an acquired A2058C mutation in rrl. The phenotypic results correlated with the expected sequencing results in 121/126 samples (96%). Phenotypic testing compared to real-time PCR resolved 2 of these discrepancies by showing the existence of both erm(41) alleles in the isolates that sequencing missed. One culture was found to be mixed with two M. abscessus subsp. as per hsp65 sequencing and 2 isolates had discordance between molecular and phenotypic results. It was presumed that 3 isolates showed discrepancy between sequencing and real-time PCR, but one culture was mixed and other 2 detected both alleles by real-time PCR leading to 100% concordance when compared to sequencing. CONCLUSION: In conclusion, real-time PCR is more accurate for detection of both acquired and induced clarithromycin resistance, specifically when mixed genic profiles are present in a sample.


Assuntos
Antibacterianos/farmacologia , Claritromicina/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Farmacorresistência Bacteriana/genética , Infecções por Mycobacterium não Tuberculosas/microbiologia , Mycobacterium abscessus/efeitos dos fármacos , Mycobacterium abscessus/genética , Reação em Cadeia da Polimerase em Tempo Real/métodos , Genes Bacterianos , Humanos , Testes de Sensibilidade Microbiana , Mutação , RNA Ribossômico 23S/genética
7.
Artigo em Inglês | MEDLINE | ID: mdl-33295480

RESUMO

Stenotrophomonas maltophilia has emerged as an important opportunistic pathogen in the last decade. Increased resistance to sulfamethoxazole/trimethoprim (SMX/TMP) has been reported in S. maltophilia strains in the past few years, leading to few therapeutic options. We conducted a prospective multicenter study at two Brazilian teaching hospitals that identified S. maltophilia isolates and evaluated their antimicrobial susceptibility profile, SMX/TMP resistance genes and their clonality profile. A total of 106 non-repeated clinical samples of S. maltophilia were evaluated. Resistance to SMX/TMP was identified in 21.6% of the samples, and previous use of SMX/TMP occurred in 19 (82.6%). PCR detected the sul1 gene in 14 of 106 strains (13.2%). Of these isolates, nine displayed resistance to SMX/TMP. The resistant strains presented a polyclonal profile. This opportunistic pathogen has emerged in immunocompromised hosts, with few therapeutic options, which is aggravated by the description of emerging resistance mechanisms, although with a polyclonal distribution profile.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana/genética , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Stenotrophomonas maltophilia/efeitos dos fármacos , Stenotrophomonas maltophilia/genética , Combinação Trimetoprima e Sulfametoxazol/farmacologia , Antibacterianos/uso terapêutico , Proteínas de Bactérias/genética , Brasil , DNA Bacteriano/genética , Farmacorresistência Bacteriana/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Hospedeiro Imunocomprometido , Testes de Sensibilidade Microbiana , Reação em Cadeia da Polimerase , Estudos Prospectivos , Stenotrophomonas maltophilia/isolamento & purificação , Resistência a Trimetoprima/genética , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico
8.
PLoS One ; 15(12): e0237283, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33259486

RESUMO

Antibiotic resistant bacteria (ARB) and their genes (ARGs) have become recognised as significant emerging environmental pollutants. ARB and ARGs in sewage sludge can be transmitted back to humans via the food chain when sludge is recycled to agricultural land, making sludge treatment key to control the release of ARB and ARGs to the environment. This study investigated the fate of antibiotic resistant Escherichia coli and a large set of antibiotic resistance genes (ARGs) during full scale anaerobic digestion (AD) of sewage sludge at two U.K. wastewater treatment plants and evaluated the impact of thermal hydrolysis (TH) pre-treatment on their abundance and diversity. Absolute abundance of 13 ARGs and the Class I integron gene intI1 was calculated using single gene quantitative (q) PCR. High through-put qPCR analysis was also used to determine the relative abundance of 370 ARGs and mobile genetic elements (MGEs). Results revealed that TH reduced the absolute abundance of all ARGs tested and intI1 by 10-12,000 fold. After subsequent AD, a rebound effect was seen in many ARGs. The fate of ARGs during AD without pre-treatment was variable. Relative abundance of most ARGs and MGEs decreased or fluctuated, with the exception of macrolide resistance genes, which were enriched at both plants, and tetracyline and glycopeptide resistance genes which were enriched in the plant employing TH. Diversity of ARGs and MGEs decreased in both plants during sludge treatment. Principal coordinates analysis revealed that ARGs are clearly distinguished according to treatment step, whereas MGEs in digested sludge cluster according to site. This study provides a comprehensive within-digestor analysis of the fate of ARGs, MGEs and antibiotic resistant E. coli and highlights the effectiveness of AD, particularly when TH is used as a pre-treatment, at reducing the abundance of most ARGs and MGEs in sludgeand preventing their release into the environment.


Assuntos
Anaerobiose/genética , Farmacorresistência Bacteriana/genética , Escherichia coli/genética , Esgotos/microbiologia , Antibacterianos/farmacologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Genes Bacterianos/genética , Genes MHC Classe I/genética , Humanos , Hidrólise/efeitos dos fármacos , Integrons/genética , Sequências Repetitivas Dispersas/genética , Macrolídeos/farmacologia , Águas Residuárias/microbiologia
9.
PLoS One ; 15(12): e0243082, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33264338

RESUMO

The aim of this study was to determine the activity and synergistic mechanisms of resveratrol in combination with chlorhexidine against carbapenem-resistant Acinetobacter baumannii clinical isolates. The activity of resveratrol plus antimicrobial agents was determined by checkerboard and time-kill assay against carbapenem-resistant A. baumannii isolated from patients at the King Chulalongkorn Memorial Hospital, Bangkok, Thailand. Overexpression of efflux pumps that mediates chlorhexidine susceptibility was characterized by the ethidium bromide accumulation assay. The effect of resveratrol on the expression of efflux pump genes (adeB, adeJ, adeG abeS, and aceI) and the two-component regulators, adeR and adeS was determined by RT-qPCR. The combination of resveratrol and chlorhexidine resulted in strong synergistic and bactericidal activity against carbapenem-resistant A. baumannii. Up-regulation of adeB and aceI was induced by chlorhexidine. However, the addition of resveratrol increased chlorhexidine susceptibility with increased intracellular accumulation of ethidium bromide in A. baumannii indicating that resveratrol acts as an efflux pump inhibitor. Expression of adeB was significantly reduced in the combination of resveratrol with chlorhexidine indicating that resveratrol inhibits the AdeB efflux pump and restores chlorhexidine effect on A. baumannii. In conclusion, reduced adeB expression in A. baumannii was mediated by resveratrol suggesting that AdeB efflux pump inhibition contributes to the synergistic mechanism of resveratrol with chlorhexidine. Our finding highlights the potential importance of resveratrol in clinical applications.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Proteínas de Bactérias/genética , Carbapenêmicos/farmacologia , Clorexidina/farmacologia , Regulação para Baixo/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Proteínas de Membrana Transportadoras/genética , Resveratrol/farmacologia , Acinetobacter baumannii/genética , Sinergismo Farmacológico , Regulação Bacteriana da Expressão Gênica/efeitos dos fármacos
10.
Elife ; 92020 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-33241997

RESUMO

Moving patients between wards and prescribing high levels of antibiotics increases the spread of bacterial infections that are resistant to treatment in hospitals.


Assuntos
Antibacterianos , Infecções Bacterianas , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Farmacorresistência Bacteriana/efeitos dos fármacos , Hospitais , Humanos , Transferência de Pacientes
11.
BMC Infect Dis ; 20(1): 848, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33198686

RESUMO

BACKGROUND: Streptococcus agalactiae (Group B Streptococcus, GBS) serotypes, sequence types, and antimicrobial resistance profile vary across different geographic locations affecting disease patterns in newborns. These differences are important considerations for vaccine development efforts and data from large countries in Africa is limited. The aim of this study was to determine serotypes and genotypes of GBS isolates from pregnant women and their newborns in Ethiopia. METHODS: A hospital based cross-sectional study was conducted at three hospitals in Ethiopia from June 2014 to September 2015. Out of 225 GBS isolates, 121 GBS were recovered, confirmed and characterized at CDC's Streptococcus Laboratory using conventional microbiology methods and whole genome sequencing. RESULTS: Of the 121 isolates, 87 were from rectovaginal samples of pregnant women, 32 from different body parts of their newborns and 2 from blood of newborns with suspected sepsis. There were 25 mother-infant pairs and 24 pairs had concordant strains. The most prevalent serotypes among mothers and/or their babies were II, Ia and V (41.5, 20.6, 19.5 and 40.6%, 25 and 15.6%, respectively). Multilocus sequence typing (MLST) on 83 isolates showed ST10 (24; 28.9%) and ST2 (12; 14.5%) as most predominant sequence types. All GBS strains were susceptible to penicillin, cefotaxime and vancomycin, which correlated to the presence of wildtype PBP2x types and the lack of known vancomycin-resistance genes. Tetracycline resistance was high (73; 88%, associated primarily with tetM, but also tetO and tetL). Five isolates (6%) were resistant to erythromycin and clindamycin and 3 isolates were fluoroquinolone-resistant, containing associated mutations in gyrA and parC genes. All isolates were positive for one of four homologous Alpha/Rib family determinants and 1-2 of the three main pilus types. CONCLUSIONS: Predominant serotypes were II, Ia, and V. A limited number of clonal types were identified with two STs accounting for about half of the isolates. All strains collected in this study were susceptible to beta-lactam antibiotics and vancomycin. Typical of most GBS, these isolates were positive for single alpha-like family protein, serine-rich repeat gene, as well as 1-2 pilus determinants.


Assuntos
Genótipo , Complicações Infecciosas na Gravidez/diagnóstico , Sorogrupo , Infecções Estreptocócicas/diagnóstico , Streptococcus agalactiae/genética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Estudos Transversais , Farmacorresistência Bacteriana/efeitos dos fármacos , Etiópia/epidemiologia , Feminino , Humanos , Recém-Nascido , Testes de Sensibilidade Microbiana , Tipagem de Sequências Multilocus , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/microbiologia , Estudos Prospectivos , Sepse/diagnóstico , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/microbiologia , Streptococcus agalactiae/isolamento & purificação , Sequenciamento Completo do Genoma
12.
Pneumologie ; 74(11): 773-779, 2020 Nov.
Artigo em Alemão | MEDLINE | ID: mdl-33202438

RESUMO

The new ATS/ERS/ESCMID/IDSA guideline answers 22 PICO questions on the treatment of lung diseases caused by Mycobacterium avium complex (MAC), M. kansasii, M. xenopi and M. abscessus. NON-TUBERCULOUS MYCOBACTERIA (NTM) LUNG DISEASE: Especially in patients with microscopic detection of acid-fast bacteria in sputum or with cavernous disease manifestation, the start of treatment should not be delayed. Treatment should be based on species-specific resistance testing (according to the CLSI guidelines). In selected patients, adjuvant surgical resection after consultation with an expert is recommended. MAC LUNG DISEASE: Therapy is based on a regimen with at least three drugs including a macrolide (rather azithromycin than clarithromycin) and ethambutol. For patients with cavitation, with pronounced nodular bronchiectatic disease or with macrolide resistance, daily oral therapy should be expanded by parenteral amikacin or streptomycin. Liposomally encapsulated amikacin for inhalation is recommended in patients with treatment failure. Patients with nodular-bronchiectatic disease manifestation should receive oral macrolide-based therapy, which - depending on the extent - can be given 3 times a week. The recommended duration is 12 months after conversion of the sputum culture. M. KANSASII LUNG DISEASE: The triple combination of rifampicin, ethambutol and macrolide (or isoniazid) is recommended for at least 12 months. In patients with rifampicin resistance or intolerance, moxifloxacin is recommended as a replacement. M. XENOPI LUNG DISEASE: The combination of rifampicin, ethambutol and macrolide (and/or moxifloxacin) is recommended for at least 12 months after conversion of the sputum culture. For patients with cavernous disease manifestation, it is recommended to add at least parenteral amikacin and to consult experts. M. ABSCESSUS LUNG DISEASE: At least 3, in the beginning rather 4 drugs are recommended for therapy. The choice of substance should be based on a in vitro resistance test. Macrolides are the basis, but should not be counted in patients with strains with inducible macrolide resistance. Due to the lack of data, no explicit recommendations are made regarding the duration of therapy; a consultation of experts is recommended.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Micobactérias não Tuberculosas/isolamento & purificação , Guias de Prática Clínica como Assunto , Escarro/microbiologia , Quimioterapia Combinada , Humanos , Macrolídeos/uso terapêutico , Infecções por Mycobacterium não Tuberculosas/diagnóstico , Micobactérias não Tuberculosas/efeitos dos fármacos
13.
PLoS Genet ; 16(11): e1009198, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33137124

RESUMO

The level of antibiotic resistance exhibited by bacteria can vary as a function of environmental conditions. Here, we report that phenazine-methosulfate (PMS), a redox-cycling compound (RCC) enhances resistance to fluoroquinolone (FQ) norfloxacin. Genetic analysis showed that E. coli adapts to PMS stress by making Fe-S clusters with the SUF machinery instead of the ISC one. Based upon phenotypic analysis of soxR, acrA, and micF mutants, we showed that PMS antagonizes fluoroquinolone toxicity by SoxR-mediated up-regulation of the AcrAB drug efflux pump. Subsequently, we showed that despite the fact that SoxR could receive its cluster from either ISC or SUF, only SUF is able to sustain efficient SoxR maturation under exposure to prolonged PMS period or high PMS concentrations. This study furthers the idea that Fe-S cluster homeostasis acts as a sensor of environmental conditions, and because its broad influence on cell metabolism, modifies the antibiotic resistance profile of E. coli.


Assuntos
Antibacterianos/farmacologia , Proteínas de Bactérias/metabolismo , Farmacorresistência Bacteriana/genética , Escherichia coli/fisiologia , Proteínas com Ferro-Enxofre/metabolismo , Fatores de Transcrição/metabolismo , Antibacterianos/uso terapêutico , Proteínas de Transporte/genética , Proteínas de Transporte/metabolismo , Antagonismo de Drogas , Farmacorresistência Bacteriana/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Regulação Bacteriana da Expressão Gênica , Humanos , Metilfenazônio Metossulfato/farmacologia , Testes de Sensibilidade Microbiana , Norfloxacino/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/genética
14.
BMC Infect Dis ; 20(1): 809, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33153450

RESUMO

BACKGROUND: Antimicrobial resistance (AMR) in Neisseria gonorrhoeae is an emerging global health threat. Surveillance of AMR in N. gonorrhoeae in the Western Pacific Region is important, as resistant strains have typically emerged from this region. There are sparse data regarding antibiotic susceptibility of N. gonorrhoeae from Vietnam. This study aimed to provide updated data on antibiotic susceptibilities in N. gonorrhoeae isolates from Hanoi, Vietnam. METHODS: From 2017 to 2019, 409 N. gonorrhoeae clinical isolates were collected at the National Hospital for Venereology and Dermatology in Hanoi, Vietnam. Antibiotic susceptibility testing was performed by disk diffusion method according to the Clinical and Laboratory Standards Institute (CLSI) protocol. The zone diameters of inhibition were recorded and interpreted according to standard CLSI criteria, except for azithromycin, due to the absence of CLSI interpretation. Categorical variables were analyzed by Chi-square and Fisher's exact tests. Linear regression was used to evaluate zones of inhibition by year. RESULTS: Among the 409 isolates, no isolates were susceptible to penicillin, 98.3% were resistant to ciprofloxacin, and all isolates were susceptible to spectinomycin. There were 122/407 (30.0%) isolates resistant to azithromycin and there was an association between resistance and year (p <  0.01), ranging from 15.3% of isolates in 2017 to 46.7% of the isolates in 2018. Resistance to cefixime was found in 13/406 (3.2%) of isolates and there was no association by year (p = 0.30). Resistance to ceftriaxone occurred in 3/408 (0.7%) of isolates. Linear regression indicated the zone of inhibition diameters decreased by 0.83 mm each year for ceftriaxone (95% CI: - 1.3, - 0.4; p <  0.01) and decreased by 0.83 mm each year (95% CI: - 1.33, - 0.33; p <  0.01) for azithromycin; the association was not significant for cefixime (p = 0.07). CONCLUSIONS: We found decreasing susceptibility of N. gonorrhoeae to ceftriaxone and azithromycin, as well as a high prevalence of resistance to azithromycin, among isolates in Hanoi, Vietnam from 2017 to 2019. The trends of decreasing susceptibility to first-line treatments are concerning and highlight the urgency of addressing antimicrobial resistance in N. gonorrhoeae. Expanded surveillance efforts within the Western Pacific Region are critical to monitoring trends and informing treatment guidelines.


Assuntos
Antibacterianos/uso terapêutico , Azitromicina/uso terapêutico , Ceftriaxona/uso terapêutico , Farmacorresistência Bacteriana/efeitos dos fármacos , Gonorreia/tratamento farmacológico , Neisseria gonorrhoeae/efeitos dos fármacos , Adolescente , Adulto , Idoso , Feminino , Gonorreia/epidemiologia , Gonorreia/microbiologia , Humanos , Laboratórios , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Neisseria gonorrhoeae/isolamento & purificação , Vietnã/epidemiologia , Adulto Jovem
15.
BMC Infect Dis ; 20(1): 813, 2020 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-33167875

RESUMO

BACKGROUND: Uncomplicated urinary tract infections (UTIs) in women are usually managed in primary care with antibiotics. However, many women seem to prefer to handle UTI symptoms with nonsteroidal anti-inflammatory drugs (NSAIDs) and other remedies. The aim of this study was to compare UTI management as recommended by physicians with the patients' management at home. METHODS: This prospective cohort study in German primary care is based on clinical data from local practices and patient questionnaires. Participating women completed a baseline data sheet in the practice; their urine sample was tested by a dipstick in the practice and cultured by a laboratory. The women reported treatment and symptom-related impairment on an eight-item symptom questionnaire daily for 7 days. Using growth curve models, we analysed the influence of time on the total severity score to examine how symptoms changed across days. We then examined whether symptom severity and symptom course differed between patients who took antibiotics or NSAIDs. RESULTS: A total of 120 women (mean age of 43.3 ± 16.6 years) were enrolled. The urine dipstick was positive for leucocytes in 92%, erythrocytes in 87%, and nitrites in 23%. Physicians prescribed antibiotics for 102 (87%) women and recommended NSAIDs in 14 cases. According to the women's reports, only 60% (72/120) took antibiotics, while the remainder took NSAIDs and other remedies. Symptoms declined from day 0 to day 6, irrespective of whether women decided to take an antibiotic, NSAIDs, none or both, as confirmed by a significant curvilinear time effect (B = 0.06, SE = 0.005, p < .001). The symptom course, however, was moderated by taking antibiotics so that the change in symptom severity was somewhat more pronounced in women taking antibiotics (B = 0.06) than in the remainder (B = 0.04). CONCLUSION: A substantial proportion of women did not follow their physicians' treatment recommendations, and many used NSAIDs. All women had a good chance of recovery irrespective of whether they decided to take antibiotics. A sensitive listening to patient preferences in the consultation may encourage physicians to recommend and prescribe symptomatic treatment with NSAID more often than antibiotic medicines.


Assuntos
Antibacterianos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Infecções por Escherichia coli/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Atenção Primária à Saúde , Encaminhamento e Consulta , Infecções Urinárias/tratamento farmacológico , Adulto , Farmacorresistência Bacteriana/efeitos dos fármacos , Infecções por Escherichia coli/microbiologia , Feminino , Humanos , Pessoa de Meia-Idade , Cooperação do Paciente , Médicos/psicologia , Estudos Prospectivos , Inquéritos e Questionários , Infecções Urinárias/microbiologia
16.
N Engl J Med ; 383(20): 1941-1950, 2020 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-33176084

RESUMO

BACKGROUND: Mass distribution of azithromycin to preschool children twice yearly for 2 years has been shown to reduce childhood mortality in sub-Saharan Africa but at the cost of amplifying macrolide resistance. The effects on the gut resistome, a reservoir of antimicrobial resistance genes in the body, of twice-yearly administration of azithromycin for a longer period are unclear. METHODS: We investigated the gut resistome of children after they received twice-yearly distributions of azithromycin for 4 years. In the Niger site of the MORDOR trial, we enrolled 30 villages in a concurrent trial in which they were randomly assigned to receive mass distribution of either azithromycin or placebo, offered to all children 1 to 59 months of age every 6 months for 4 years. Rectal swabs were collected at baseline, 36 months, and 48 months for analysis of the participants' gut resistome. The primary outcome was the ratio of macrolide-resistance determinants in the azithromycin group to those in the placebo group at 48 months. RESULTS: Over the entire 48-month period, the mean (±SD) coverage was 86.6±12% in the villages that received placebo and 83.2±16.4% in the villages that received azithromycin. A total of 3232 samples were collected during the entire trial period; of the samples obtained at the 48-month monitoring visit, 546 samples from 15 villages that received placebo and 504 from 14 villages that received azithromycin were analyzed. Determinants of macrolide resistance were higher in the azithromycin group than in the placebo group: 7.4 times as high (95% confidence interval [CI], 4.0 to 16.7) at 36 months and 7.5 times as high (95% CI, 3.8 to 23.1) at 48 months. Continued mass azithromycin distributions also selected for determinants of nonmacrolide resistance, including resistance to beta-lactam antibiotics, an antibiotic class prescribed frequently in this region of Africa. CONCLUSIONS: Among villages assigned to receive mass distributions of azithromycin or placebo twice yearly for 4 years, antibiotic resistance was more common in the villages that received azithromycin than in those that received placebo. This trial showed that mass azithromycin distributions may propagate antibiotic resistance. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov number, NCT02047981.).


Assuntos
Antibacterianos/administração & dosagem , Azitromicina/administração & dosagem , Farmacorresistência Bacteriana/efeitos dos fármacos , Microbioma Gastrointestinal/efeitos dos fármacos , Macrolídeos/farmacologia , Administração Massiva de Medicamentos , Antibacterianos/farmacologia , Azitromicina/farmacologia , Mortalidade da Criança , Pré-Escolar , Farmacorresistência Bacteriana/genética , Feminino , Humanos , Lactente , Macrolídeos/uso terapêutico , Masculino , Metagenoma , Níger , Análise de Sequência de DNA
17.
Int J Food Microbiol ; 335: 108893, 2020 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-33007603

RESUMO

Food-producing animals are considered a leading source of human Salmonella infections in Korea. However, there is a lack of comprehensive and up-to-date data regarding the diversity and resistance profiles of Salmonella serotypes in these animals. Therefore, this study aimed to determine the distribution and antimicrobial resistance profiles of Salmonella serotypes isolated from cattle, pigs, and chickens in Korea between 2010 and 2018. A total of 3018 Salmonella isolates were obtained from 16 laboratories/centers participating in the Korean Veterinary Antimicrobial Resistance Monitoring System. Salmonella serotypes were identified from the following isolates: 179 cattle (17 serotypes), 959 pig (45 serotypes), and 1880 chicken (64 serotypes). The most frequent serotypes in cattle (Typhimurium, Salmonella 4,[5],12:i:-, and Schwarzengrund), pigs (Typhimurium, Rissen, and S. 4,[5],12:i:-), and chickens (Enteritidis, Albany, Virchow, and Montevideo) accounted for more than 50% of the total serotypes in the respective animal species. To the best of our knowledge, Salmonella 4,[5],12:i:- has not been identified in cattle in Korea to date. More than 80% of the isolates demonstrated resistance to at least one antimicrobial agent. Multidrug-resistance was found in almost half of the serotypes; the highest proportion in cattle (59.2%), followed by pigs (53.4%), and chickens (45.7%). Significant proportions of the serotypes were resistant to ampicillin, streptomycin, and tetracycline. Ceftiofur and ciprofloxacin resistance rates were the highest in Salmonella isolated from chickens (17.1% and 4.1%, respectively) and cattle (10.1% and 3.9%, respectively) compared to that in pigs. Among the frequent serotypes, Albany demonstrated the highest resistance rate (>90%) to five different antimicrobials. Alarmingly, some Salmonella serotypes that are frequently associated with human infections demonstrated a trend of increasing resistance to critically important antibiotics, including 3rd generation cephalosporins and quinolones. Collectively, the presence of antibiotic-resistant Salmonella in food-producing animals poses a potential risk to public health.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Salmonelose Animal/microbiologia , Salmonella/classificação , Salmonella/efeitos dos fármacos , Animais , Bovinos , Galinhas , Farmacorresistência Bacteriana/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , República da Coreia/epidemiologia , Salmonella/isolamento & purificação , Salmonelose Animal/epidemiologia , Sorogrupo , Suínos
18.
J Environ Public Health ; 2020: 2796365, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33014080

RESUMO

World Health Organizations launched a global action plan on antimicrobial resistance since 2015. Along with other objectives, the plan was aimed to strengthen knowledge of the spread of antimicrobial resistance through surveillance and research. Given their high bacterial densities and that they receive antibiotics, metals, and other selective agents, wastewater systems are a logical hotspot for antibiotic resistance surveillance. The current study reports on the result of antibiotic resistance surveillance conducted in selected wastewater systems of Eastern Ethiopia from Feb. 2018 to Oct. 2019. We monitored three wastewater systems in Eastern Ethiopia, such as the activated sludge system of Dire Dawa University, waste stabilization pond of Haramaya University, and a septic tank of Hiwot Fana Specialized University Hospital for 18 months period. We collected 66 wastewater samples from 11 sampling locations and isolated 722 bacteria using selective culture media and biochemical tests. We tested their antibiotic susceptibility using the standard Kirby-Bauer disk diffusion method on the surface of the Mueller-Hinton agar and interpreted the result according to EUCAST guidelines. The result shows the highest percentage of resistance for ampicillin among isolates of hospital wastewater effluent which is 36 (94.7%), 33 (91.7%), and 32 (88.9%) for E. coli, E. faecalis, and E. faecium, respectively. A lower rate of resistance was seen for gentamicin among isolates of activated sludge wastewater treatment system which is 10 (16.4%), 8 (13.3%), 11 (18.9%), and 12 (20.3%) for E. coli, E. faecalis, E. faecium, and P. aeruginosa, respectively. Hospital wastewater exhibited higher resistance than the other two wastewater systems. The Multiple Antibiotic Resistance Index (MARI) has significantly increased in the wastewater's course treatment process, showing the proliferation of resistance in the wastewater treatment system.


Assuntos
Bactérias/isolamento & purificação , Farmacorresistência Bacteriana , Águas Residuárias/microbiologia , Antibacterianos/farmacologia , Bactérias/classificação , Bactérias/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Monitoramento Ambiental , Etiópia/epidemiologia , Humanos , Testes de Sensibilidade Microbiana
19.
J Environ Public Health ; 2020: 3439497, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33082791

RESUMO

Background: Antimicrobial resistance among community-acquired uropathogens is an emerging concern over the past decades that warrants a continuing reevaluation of the appropriateness of recommended empiric antimicrobial regimens for treatment of urinary tract infections (UTIs). Aims: To describe the microbial spectrum and resistance profile of community-acquired uropathogens and predictors of isolation of resistant strains. Methods: Between October 2017 and June 2019, individuals who visited the outpatient clinics for diagnosis of UTIs or screening of asymptomatic bacteriuria were included in the study if they were tested for urine culture in one of the three main medical diagnostic laboratories of Mashhad, Iran. The standard disk diffusion antimicrobial susceptibility testing was used, with the Clinical and Laboratory Standards Institute (CLSI) threshold cutoffs for susceptibility of isolated uropathogens. Results: Three hundred thirty cases were included with a median age of 47 years. Two hundred seventy-six (83.6%) were female. The most common isolated uropathogens were Escherichia coli in 201 (60.9%) cases and Klebsiella species in 46 (13.9%) cases. E. coli isolates showed the highest rates of susceptibility to nitrofurantoin (89.3%), cefixime (75%), and gentamicin (72.4%). Exposure to antibiotics in the past 3 months was a predictor of resistance to ciprofloxacin (OR: 2.8, 95% CI: 1.33-6.28), and older age was a predictor of resistance to TMP-SMX (OR: 2.1, 95% CI: 1.07-3.97) among E. coli isolates. Conclusion. E. coli and Klebsiella species accounted for about two-thirds of community-acquired uropathogens. In regard to the high susceptibility rates, nitrofurantoin was identified as the first-choice agent for empiric treatment of community-acquired cystitis, while cefixime and gentamicin might be the second-choice alternatives. Ciprofloxacin and TMP-SMX, on the other hand, cannot be considered appropriate agents for empiric therapy of community-acquired UTIs, particularly in those who had exposure to antibiotics in the past 3 months and the elderly.


Assuntos
Antibacterianos/farmacologia , Bactérias/isolamento & purificação , Farmacorresistência Bacteriana , Infecções Urinárias/microbiologia , Adulto , Antibacterianos/uso terapêutico , Bactérias/classificação , Bactérias/efeitos dos fármacos , Infecções Comunitárias Adquiridas/tratamento farmacológico , Infecções Comunitárias Adquiridas/epidemiologia , Infecções Comunitárias Adquiridas/microbiologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Feminino , Humanos , Irã (Geográfico)/epidemiologia , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Fatores de Risco , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/epidemiologia
20.
PLoS Pathog ; 16(10): e1008529, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-33125434

RESUMO

Biofilm-based infections are difficult to treat due to their inherent resistance to antibiotic treatment. Discovering new approaches to enhance antibiotic efficacy in biofilms would be highly significant in treating many chronic infections. Exposure to aminoglycosides induces adaptive resistance in Pseudomonas aeruginosa biofilms. Adaptive resistance is primarily the result of active antibiotic export by RND-type efflux pumps, which use the proton motive force as an energy source. We show that the protonophore uncoupler triclosan depletes the membrane potential of biofilm growing P. aeruginosa, leading to decreased activity of RND-type efflux pumps. This disruption results in increased intracellular accumulation of tobramycin and enhanced antimicrobial activity in vitro. In addition, we show that triclosan enhances tobramycin effectiveness in vivo using a mouse wound model. Combining triclosan with tobramycin is a new anti-biofilm strategy that targets bacterial energetics, increasing the susceptibility of P. aeruginosa biofilms to aminoglycosides.


Assuntos
Aminoglicosídeos/farmacologia , Biofilmes/efeitos dos fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Potenciais da Membrana/efeitos dos fármacos , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/efeitos dos fármacos , Triclosan/farmacologia , Animais , Anti-Infecciosos Locais/farmacologia , Biofilmes/crescimento & desenvolvimento , Feminino , Masculino , Camundongos , Camundongos Pelados , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/crescimento & desenvolvimento
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