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1.
BMC Infect Dis ; 21(1): 16, 2021 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-33407206

RESUMEN

BACKGROUND: Epidemiological data of cephalosporin-resistant Enterobacterales in Sub-Saharan Africa is still restricted, and in particular in Mozambique. The aim of this study was to detect and characterize extended-spectrum ß-lactamase (ESBL) - and plasmid-mediated AmpC (pAmpC)-producing clinical strains of Escherichia coli at Maputo Central Hospital (MCH), a 1000-bed reference hospital in Maputo, Mozambique. METHODS: A total of 230 clinical isolates of E. coli from urine (n = 199) and blood cultures (n = 31) were collected at MCH during August-November 2015. Antimicrobial susceptibility testing was performed by the disc diffusion method and interpreted according to EUCAST guidelines. Isolates with reduced susceptibility to 3rd generation cephalosporins were examined further; phenotypically for an ESBL-/AmpC-phenotype by combined disc methods and genetically for ESBL- and pAmpC-encoding genes by PCR and partial amplicon sequencing as well as genetic relatedness by ERIC-PCR. RESULTS: A total of 75 isolates with reduced susceptibility to cefotaxime and/or ceftazidime (n = 75) from urine (n = 58/199; 29%) and blood (n = 17/31; 55%) were detected. All 75 isolates were phenotypically ESBL-positive and 25/75 (33%) of those also expressed an AmpC-phenotype. ESBL-PCR and amplicon sequencing revealed a majority of blaCTX-M (n = 58/75; 77%) dominated by blaCTX-M-15. All AmpC-phenotype positive isolates (n = 25/75; 33%) scored positive for one or more pAmpC-genes dominated by blaMOX/FOX. Multidrug resistance (resistance ≥ three antibiotic classes) was observed in all the 75 ESBL-positive isolates dominated by resistance to trimethoprim-sulfamethoxazole, ciprofloxacin and gentamicin. ERIC-PCR revealed genetic diversity among strains with minor clusters indicating intra-hospital spread. CONCLUSION: We have observed a high prevalence of MDR pAmpC- and/or ESBL-producing clinical E. coli isolates with FOX/MOX and CTX-Ms as the major ß-lactamase types, respectively. ERIC-PCR analyses revealed genetic diversity and some clusters indicating within-hospital spread. The overall findings strongly support the urgent need for accurate and rapid diagnostic services to guide antibiotic treatment and improved infection control measures.


Asunto(s)
Antibacterianos/uso terapéutico , Proteínas Bacterianas/genética , Cefotaxima/uso terapéutico , Ceftazidima/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/genética , Infecciones por Escherichia coli/tratamiento farmacológico , Escherichia coli/enzimología , Escherichia coli/aislamiento & purificación , Plásmidos/metabolismo , beta-Lactamasas/genética , Infección Hospitalaria/diagnóstico , Infección Hospitalaria/microbiología , Infecciones por Escherichia coli/sangre , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/orina , Humanos , Pruebas de Sensibilidad Microbiana , Mozambique/epidemiología , Fenotipo , Prevalencia
2.
Food Chem ; 341(Pt 1): 128171, 2021 Mar 30.
Artículo en Inglés | MEDLINE | ID: mdl-33035856

RESUMEN

Emergence of antimicrobial drug-resistance amongst food-borne pathogens has led to severe deficit of available therapeutics and requires novel interventions. This study determined the activity of vitamin C (VitC), a natural antioxidant as powerful antibacterial agent against multidrug-resistant (MDR), biofilm-forming E. coli. Our findings revealed that VitC wield antibacterial action in dose-time dependent manner with minimum inhibitory concentration (MIC) of 125 mM. At these concentrations VitC impaired quorum sensing (QS) and exopolysaccharide (EPS) production and induced sugar and protein leakage from the bacterial cells by virtue of reactive oxygen species (ROS) generation. Furthermore, VitC-treated bacteria showed downregulation of genes underpinning biofilm signaling (luxS) and regulation (bssR) by up to 27-folds. Finally, this study demonstrated the promising antimicrobial application of VitC, in situ, in Indian soft cheese (paneer) when applied as a coating. Therefore, VitC can be applied as natural and safe 'antimicrobial' against biofilm-forming bacteria in food systems vis-à-vis other conventional antimicrobials.


Asunto(s)
Antibacterianos/farmacología , Ácido Ascórbico/farmacología , Escherichia coli/efectos de los fármacos , Polisacáridos Bacterianos/metabolismo , Antibacterianos/administración & dosificación , Ácido Ascórbico/administración & dosificación , Proteínas Bacterianas/genética , Biopelículas/efectos de los fármacos , Liasas de Carbono-Azufre/genética , Queso/microbiología , Relación Dosis-Respuesta a Droga , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Escherichia coli/fisiología , Manipulación de Alimentos , Microbiología de Alimentos , Regulación Bacteriana de la Expresión Génica/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Percepción de Quorum/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo
3.
Pharmacol Ther ; 217: 107663, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-32805298

RESUMEN

While the world is grappling with the consequences of a global pandemic related to SARS-CoV-2 causing severe pneumonia, available evidence points to bacterial infection with Streptococcus pneumoniae as the most common cause of severe community acquired pneumonia (SCAP). Rapid diagnostics and molecular testing have improved the identification of co-existent pathogens. However, mortality in patients admitted to ICU remains staggeringly high. The American Thoracic Society and Infectious Diseases Society of America have updated CAP guidelines to help streamline disease management. The common theme is use of timely, appropriate and adequate antibiotic coverage to decrease mortality and avoid drug resistance. Novel antibiotics have been studied for CAP and extend the choice of therapy, particularly for those who are intolerant of, or not responding to standard treatment, including those who harbor drug resistant pathogens. In this review, we focus on the risk factors, microbiology, site of care decisions and treatment of patients with SCAP.


Asunto(s)
Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/microbiología , Manejo de la Enfermedad , Unidades de Cuidados Intensivos , Neumonía/tratamiento farmacológico , Neumonía/microbiología , Infecciones Comunitarias Adquiridas/mortalidad , Farmacorresistencia Bacteriana Múltiple , Guías como Asunto , Humanos , Neumonía/mortalidad
4.
J Appl Microbiol ; 130(1): 50-60, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32594639

RESUMEN

AIM: Emergence of extended antibiotic resistance among several human bacterial pathogens often leads to the failure of existing antibiotics to treat bacterial infections worldwide. Hence, the present study is aimed to explore antibacterial activity of marine cyanobacterium against MDR pathogens. METHODS AND RESULTS: The cyanobacterial samples were collected and isolated from Thondi Palk Strait region. The isolate was subjected to polarity based solvent extraction and checked for their antibacterial activity against test bacterial pathogens. The active principles from chloroform extract of Oxynema thaianum (CEOT) were partially purified through thin layer chromatography (TLC). The active principle with highest activity was further characterized by FTIR, high performance liquid chromatography (HPLC) and gas chromatography mass spectrometry (GC-MS) analysis. Among the eight extracts tested, CEOT showed effective zone of clearance against ESBL producing Escherichia coli and Klebsiella pneumoniae in disc diffusion method. In TLC, all the purified five fractions were eluted and tested for their antibacterial activity against test pathogens. The third fraction showing maximum activity was subjected to HPLC analysis for checking its purity. In GC-MS analysis, 9-octadecenoic acid, methyl ester and hexadecanoic acid were identified as the major chemical compounds. CONCLUSION: Hence, the present study was concluded that O. thaianum ALU PBC5 is a promising agent to treat ESBL producing MDR bacterial pathogens. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the pioneer study on screening and isolation of bioactive compounds from the marine cyanobacteria against MDR pathogens such as E. coli and K. pneumoniae. Here, 9-octadecenoic acid, methyl ester and hexadecanoic acid were identified as the major chemical compounds through TLC, FTIR, HPLC and GC-MS. From this screen, we identified the bioactive compounds against ESBL producing multidrug resistant pathogens such as E. coli and K. pneumoniae.


Asunto(s)
Antibacterianos/farmacología , Cianobacterias/química , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Enterobacteriaceae/efectos de los fármacos , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Cloroformo/química , Enterobacteriaceae/enzimología , Humanos , Pruebas de Sensibilidad Microbiana , beta-Lactamasas/metabolismo
5.
Life Sci ; 264: 118675, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33127513

RESUMEN

Among the bacterial resistance mechanisms, efflux pumps are responsible for expelling xenobiotics, including bacterial cell antibiotics. Given this problem, studies are investigating new alternatives for inhibiting bacterial growth or enhancing the antibiotic activity of drugs already on the market. With this in mind, this study aimed to evaluate the antibacterial activity of Estragole against the RN4220 Staphylococcus aureus strain, which carries the MsrA efflux pump, as well as Estragole's toxicity in the Drosophila melanogaster arthropod model. The broth microdilution method was used to perform the Minimum Inhibitory Concentration (MIC) tests. Estragole was used at a Sub-Inhibitory Concentration (MIC/8) in association with erythromycin and ethidium bromide to assess its combined effect. As for Estragole's toxicity evaluation over D. melanogaster, the fumigation bioassay and negative geotaxis methods were used. The results were expressed as an average of sextuplicate replicates. A Two-way ANOVA followed by Bonferroni's post hoc test was used. The present study demonstrated that Estragole did not show a direct antibacterial activity over the RN4220 S. aureus strain, since it obtained a MIC ≥1024 µg/mL. The association of estragole with erythromycin demonstrated a potentiation of the antibiotic effect, reducing the MIC from 512 to 256 µg/mL. On the other hand, when estragole was associated with ethidium bromide (EtBr), an antagonism was observed, increasing the MIC of EtBr from 32 to 50.7968 µg/mL, demonstrating that estragole did not inhibited directly the MsrA efflux pump mechanism. We conclude that estragole has no relevant direct effect over bacterial growth, however, when associated with erythromycin, this reduced its MIC, potentiating the effect of the antibiotic.


Asunto(s)
Anisoles/toxicidad , Antibacterianos/toxicidad , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Animales , Anisoles/administración & dosificación , Antibacterianos/administración & dosificación , Relación Dosis-Respuesta a Droga , Drosophila melanogaster , Farmacorresistencia Bacteriana Múltiple/fisiología , Eritromicina/administración & dosificación , Aromatizantes/administración & dosificación , Aromatizantes/toxicidad , Pruebas de Sensibilidad Microbiana/métodos , Staphylococcus aureus/fisiología
6.
Chemosphere ; 262: 127768, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32777611

RESUMEN

Heavy metals and antimicrobial resistant bacteria in livestock and poultry environments can cause declines in production and significant economic losses, leading to potential environmental and public health issues. In this study, the heavy metal pollution status of livestock breeding water bodies in the Dawen river basin of Shandong Province in China was evaluated, and a total of 10 heavy metals were measured. In addition, antimicrobial susceptibility tests were conducted for Escherichia coli strains isolated from the water samples. The results showed that among all the metals, copper, zinc, and iron were detected at each sampling point, followed by nickel (detection rate of 95.74%), arsenic (detection rate of 89.36%), selenium (detection rate of 68.09%), lead (detection rate of 27.66%), and mercury (detection rate of 12.77%). Cadmium and hexavalent chromium were not detected. The contents of nine heavy metals were below the existing water standard values in China, whereas the iron pollution index in the water body in the study area was large and may pose a potential risk. A total of 17 E. coli isolates showed different resistance to ß-lactams, aminoglycosides, tetracyclines, quinolone antibiotics and chloramphenicol, but were mainly resistant to ß-lactams and tetracyclines. The detection rate of the tetA resistance gene was relatively high, indicating the overuse of cephalosporins and tetracyclines. The results of the present study might provide evidence of metal pollution and theoretical basis on the treatment of colibacillosis in the livestock industries.


Asunto(s)
Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Monitoreo del Ambiente/métodos , Escherichia coli/aislamiento & purificación , Metales Pesados/análisis , Aguas Residuales/química , Contaminantes Químicos del Agua/análisis , Antibacterianos/farmacología , China , Industria Lechera , Farmacorresistencia Bacteriana Múltiple/genética , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Granjas , Ríos/química , Ríos/microbiología , Aguas Residuales/microbiología
7.
PLoS One ; 15(12): e0238084, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33284819

RESUMEN

The increasing occurrence of multidrug-resistant Enterobacteriaceae in clinical and environmental settings has been seen globally as a complex public health challenge, mostly in the developing nations where they significantly impact freshwater used for a variety of domestic purposes and irrigation. This paper detail the occurrence and antibiogram signatures of the Enterobacteriaceae community in Tsomo and Tyhume rivers within the Eastern Cape Province, the Republic of South Africa, using standard methods. The average distribution of the presumptive Enterobacteriaceae in the rivers ranged from 1 × 102 CFU/100ml to 1.95 × 104 CFU/100ml. We confirmed 56 (70.8%) out of 79 presumptive Enterobacteriaceae isolated being species within the family Enterobacteriaceae through the Matrix-Assisted Laser Desorption Ionization Time of Flight technique. Citrobacter-, Enterobacter-, Klebsiella species, and Escherichia coli were selected (n = 40) due to their pathogenic potentials for antibiogram profiling. The results of the antibiotic susceptibility testing gave a revelation that all the isolates were phenotypically multidrug-resistant. The resistance against ampicillin (95%), tetracycline and doxycycline (88%), and trimethoprim-sulfamethoxazole (85%) antibiotics were most prevalent. The Multiple Antibiotic Resistance indices stretched from 0.22 to 0.94, with the highest index observed in a C. freundii isolate. Molecular characterisation using the PCR technique revealed the dominance of blaTEM (30%; 12/40) among the eight groups of ß-lactams resistance determinants assayed. The prevalence of others was blaCTX-M genes including group 1, 2 and 9 (27.5%), blaSHV (20%), blaOXA-1-like (10%), blaPER (2.5%), and blaVEB (0%). The frequencies of the resistance determinants for the carbapenems were blaKPC (17.6%), blaGES (11.8%), blaIMP (11.8%), blaVIM (11.8%), and blaOXA-48-like (5.9%). Out of the six plasmid-mediated AmpC (pAmpC) genes investigated blaACC, blaEBC, blaFOX, blaCIT, blaDHA, and blaMOX, only the first four were detected. In this category, the most dominant was blaEBC, with 18.4% (7/38). The prevalence of the non-ß-lactamases include tetA (33.3%), tetB (30.5%), tetC (2.8%), tetD (11.1%), tetK (0%), tetM (13.9%), catI (12%), catII (68%), sulI (14.3%), sulII (22.9%) and aadA (8.3%). Notably, a C. koseri harboured 42.8% (12/28) of the genes assayed for which includes five of the ESBL genes (including the only blaPER detected in this study), two of the pAmpC resistance genes (blaACC and blaCIT), and five of the non-ß-lactamase genes. This study gives the first report on C. koseri exhibiting the co-occurrence of ESBL/AmpC ß-lactamase genes from the environment to the best of our knowledge. The detection of a blaPER producing Citrobacter spp. in this study is remarkable. These findings provide evidence that freshwater serves as reservoirs of antimicrobial resistance determinants, which can then be easily transferred to human beings via the food chain and water.


Asunto(s)
Enterobacteriaceae/genética , Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/genética , Enterobacteriaceae/efectos de los fármacos , Pruebas de Sensibilidad Microbiana/métodos , Plásmidos/genética , Ríos , Sudáfrica , Resistencia betalactámica/efectos de los fármacos , Resistencia betalactámica/genética
8.
Elife ; 92020 12 17.
Artículo en Inglés | MEDLINE | ID: mdl-33331820

RESUMEN

Here, we describe the case of a COVID-19 patient who developed recurring ventilator-associated pneumonia caused by Pseudomonas aeruginosa that acquired increasing levels of antimicrobial resistance (AMR) in response to treatment. Metagenomic analysis revealed the AMR genotype, while immunological analysis revealed massive and escalating levels of T-cell activation. These were both SARS-CoV-2 and P. aeruginosa specific, and bystander activated, which may have contributed to this patient's persistent symptoms and radiological changes.


Asunto(s)
Antibacterianos/uso terapéutico , Activación de Linfocitos , Neumonía Asociada al Ventilador/tratamiento farmacológico , Infecciones por Pseudomonas/tratamiento farmacológico , Linfocitos T/inmunología , Antibacterianos/farmacología , /terapia , Farmacorresistencia Bacteriana Múltiple , Humanos , Pulmón/microbiología , Masculino , Meropenem/farmacología , Meropenem/uso terapéutico , Metagenómica , Persona de Mediana Edad , Combinación Piperacilina y Tazobactam/farmacología , Combinación Piperacilina y Tazobactam/uso terapéutico , Neumonía Asociada al Ventilador/diagnóstico por imagen , Neumonía Asociada al Ventilador/etiología , Infecciones por Pseudomonas/diagnóstico por imagen , Infecciones por Pseudomonas/etiología , Pseudomonas aeruginosa/aislamiento & purificación , Recurrencia , Respiración Artificial
9.
Viruses ; 12(12)2020 12 19.
Artículo en Inglés | MEDLINE | ID: mdl-33352791

RESUMEN

Worldwide, poultry industry suffers from infections caused by avian pathogenic Escherichia coli. Therapeutic failure due to resistant bacteria is of increasing concern and poses a threat to human and animal health. This causes a high demand to find alternatives to fight bacterial infections in animal farming. Bacteriophages are being especially considered for the control of multi-drug resistant bacteria due to their high specificity and lack of serious side effects. Therefore, the study aimed on characterizing phages and composing a phage cocktail suitable for the prevention of infections with E. coli. Six phages were isolated or selected from our collections and characterized individually and in combination with regard to host range, stability, reproduction, and efficacy in vitro. The cocktail consisting of six phages was able to inhibit formation of biofilms by some E. coli strains but not by all. Phage-resistant variants arose when bacterial cells were challenged with a single phage but not when challenged by a combination of four or six phages. Resistant variants arising showed changes in carbon metabolism and/or motility. Genomic comparison of wild type and phage-resistant mutant E28.G28R3 revealed a deletion of several genes putatively involved in phage adsorption and infection.


Asunto(s)
Infecciones por Escherichia coli/prevención & control , Terapia de Fagos , Enfermedades de las Aves de Corral/prevención & control , Animales , Bacteriólisis , Bacteriófagos/genética , Biopelículas , Farmacorresistencia Bacteriana Múltiple , Infecciones por Escherichia coli/veterinaria , Genoma Viral , Humanos
10.
PLoS One ; 15(12): e0243128, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33264364

RESUMEN

BACKGROUND: Diarrhea is one of the leading causes of mortality in children under five globally. When it is associated with bacteremia, mortality is even higher. However, bacteraemia in diarrheal children has gained little attention in spite of its deleterious impact in under-five mortality. So, we aimed to evaluate associated clinical and laboratory factors for death in under-five children hospitalized with both diarrhea and bacteremia. METHODS: In this retrospective cross-sectional study, we used patients' electronic database of Dhaka Hospital of 'icddr,b', and enrolled all under-five children with diarrhea and bacterial growth in their blood samples on admission between June-2014 and May-2017. Clinical and laboratory characteristics were compared between those who died and who survived with a special attention to bacterial pathogens related to deaths and their sensitivity pattern. RESULTS: In a total of 401 diarrheal children with bacteraemia, 45 (11%) died. Although Salmonella Typhi (34%) was the most predominant isolate followed by Staphylococcus species (16%) and Pseudomonas species (9%), children who died more often had E. coli (OR = 5.69, 95% CI = 2.42-13.39, p = <0.001) and Klebsiella bacteraemia (OR = 4.59, 95% CI = 1.84-11.46, p = 0.001) compared to those who survived. However, none of them was significantly associated with deaths in regression analysis when adjusted with other potential confounders. E. coli was 100% resistant to ampicillin, 41% to gentamicin, and 73% to ceftriaxone and Klebsiella species was 96% resistant to ampicillin, 42% to gentamicin, and 62% to ceftriaxone. Study children who died had significantly higher overall resistance pattern shown in World Health Organization (WHO) recommended one of the first line antibiotics in treating childhood sepsis such as ampicillin (80% vs. 50%, p = 0.001) and in second line antibiotic such as ceftriaxone (49% vs. 22%, p = 0.001) compared to the survivors. In logistic regression analysis, after adjusting for potential confounders, we found that clinical sepsis (aOR 3.79, 95% CI 1.60-8.96, p = 0.002), hypoxemia (aOR 4.20, 95% CI 1.74-10.12, p = 0.001), and hyperkalaemia (aOR 2.69, 95% CI 1.05-6.91, p = 0.039) were found to be independent predictors of deaths and receipt of sensitive antibiotic (aOR 0.42, 95% CI 0.18-0.99, p = 0.048) was revealed as the independent protective factor for deaths in this population. CONCLUSION AND SIGNIFICANCE: The results of our data suggest that diarrheal children with bacteremia who died more often had gram negative bacteremia compared to those who survived and these pathogens are highly resistant to WHO recommended first line and second line antibiotics. The results further emphasize the critical importance of early identification of important clinical problems such as clinical sepsis, hypoxemia and hyperkalaemia in diarrheal children and treat them with potential sensitive antibiotic(s) in order to reduce bacteremia related mortality in children with diarrhea, especially in resource limited settings.


Asunto(s)
Antibacterianos/farmacología , Bacteriemia/mortalidad , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Diarrea/microbiología , Klebsiella , Bacteriemia/microbiología , Bacterias/clasificación , Bangladesh/epidemiología , Preescolar , Estudios Transversales , Diarrea/mortalidad , Farmacorresistencia Bacteriana Múltiple , Escherichia coli/efectos de los fármacos , Escherichia coli/aislamiento & purificación , Femenino , Hospitalización , Humanos , Lactante , Recién Nacido , Klebsiella/efectos de los fármacos , Klebsiella/aislamiento & purificación , Masculino , Pseudomonas/efectos de los fármacos , Pseudomonas/aislamiento & purificación , Estudios Retrospectivos , Salmonella typhi/efectos de los fármacos , Salmonella typhi/aislamiento & purificación , Staphylococcus/efectos de los fármacos , Staphylococcus/aislamiento & purificación , Análisis de Supervivencia
11.
PLoS One ; 15(12): e0243054, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33284828

RESUMEN

BACKGROUND: Infections caused by antibiotic-resistant bacteria results in high rates of morbidity and mortality. Although the prolonged cotrimoxazole (CTX) prophylaxis is arguably associated with the risk of increasing drug resistance in the common pathogens, information regarding its impact on Streptococci pneumoniae / pneumococcus is very limited. OBJECTIVE: This study was conducted to investigate the effect of cotrimoxazole prophylaxis on nasopharyngeal colonization rate and antimicrobial resistance using Streptococci pneumoniae (pneumococcus) as an indicator organism among HIV patients in Arba Minch, Ethiopia. MATERIALS AND METHODS: A comparative cross-sectional study was designed and conducted among HIV patients attending the Anti-Retroviral Treatment (ART) clinic of Arba Minch General Hospital (AMGH) from April 01 to August 31, 2018. A total of 252 participants were systematically selected and clustered into two study groups based on their CTX prophylaxis status, one taking CTX prophylaxis, and the second one, the control group (without prophylaxis). A structured questionnaire was used to collect socio-demographic and clinical data from patients. A nasopharyngeal swab was collected and cultured for pneumococcal isolation and identification in accordance with standard microbiological techniques. An antibiotics sensitivity test was performed according to the CLSI guidelines. Data were analyzed using the Statistical package for social science (SPSS) version 20. The primary outcome was determined using logistic regression analysis. RESULTS: Of the 252 enrolled HIV patients (mean age (37.38± 9.03 years), 144 (57.14%) were males. The overall, nasopharyngeal colonization rate of S. pneumoniae was 13.5% (95% CI: 8.4-15.6). Asymptomatic pneumococcal carriage rates among patients on CTX prophylaxis and the control group were 16.3%, and 10.3% respectively (p-value = 0.03). Regarding the risk factors analyzed, CTX prophylaxis (AOR: 2.2; 95% CI: 1.05-4.9) and gender (AOR: 2.5; 95% CI: 1.09-5.93) were significantly associated with pneumococcal colonization, showing a male preponderance. Cotrimoxazole-resistant pneumococci were 85.7% vs. 47.4% in the prophylaxis group and the control group respectively and it was statistically significant (AOR: 6.7; 95% CI: 1.3-36). Percentages of multi-drug resistant isolates in these two groups were 38.09 and 15.38 respectively (p-value = 0.04). Among the CTX resistant pneumococci isolates, 85% were also found to be co-resistant towards penicillin and was statistically significant. CONCLUSION: The percentage prevalence of nasopharyngeal pneumococci colonization was higher in patients taking CTX prophylaxis. It was noted that CTX prophylaxis eventually results in the selection of cotrimoxazole resistance and multi-drug resistance in pneumococci. There is evidence of existing cross-resistance between cotrimoxazole and penicillin antibiotics. Therefore, CTX prophylaxis must be administered judiciously. Surveillance for antimicrobial susceptibility is warranted where the prophylaxis is common.


Asunto(s)
Portador Sano/epidemiología , Farmacorresistencia Bacteriana Múltiple , Infecciones por VIH/tratamiento farmacológico , Infecciones Neumocócicas/diagnóstico , Streptococcus pneumoniae/aislamiento & purificación , Combinación Trimetoprim y Sulfametoxazol/administración & dosificación , Adulto , Fármacos Anti-VIH/uso terapéutico , Profilaxis Antibiótica , Portador Sano/microbiología , Estudios de Casos y Controles , Estudios Transversales , Etiopía , Femenino , Infecciones por VIH/microbiología , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Nasofaringe/microbiología , Infecciones Neumocócicas/prevención & control , Caracteres Sexuales , Streptococcus pneumoniae/efectos de los fármacos , Streptococcus pneumoniae/crecimiento & desarrollo , Combinación Trimetoprim y Sulfametoxazol/farmacología
12.
Nat Commun ; 11(1): 6284, 2020 12 08.
Artículo en Inglés | MEDLINE | ID: mdl-33293519

RESUMEN

The MerR-family proteins represent a unique family of bacteria transcription factors (TFs), which activate transcription in a manner distinct from canonical ones. Here, we report a cryo-EM structure of a B. subtilis transcription activation complex comprising B. subtilis six-subunit (2αßß'ωε) RNA Polymerase (RNAP) core enzyme, σA, a promoter DNA, and the ligand-bound B. subtilis BmrR, a prototype of MerR-family TFs. The structure reveals that RNAP and BmrR recognize the upstream promoter DNA from opposite faces and induce four significant kinks from the -35 element to the -10 element of the promoter DNA in a cooperative manner, which restores otherwise inactive promoter activity by shortening the length of promoter non-optimal -35/-10 spacer. Our structure supports a DNA-distortion and RNAP-non-contact paradigm of transcriptional activation by MerR TFs.


Asunto(s)
Bacillus subtilis/genética , Proteínas Bacterianas/metabolismo , Farmacorresistencia Bacteriana Múltiple/genética , Regulación Bacteriana de la Expresión Génica , Transactivadores/metabolismo , Activación Transcripcional , Bacillus subtilis/efectos de los fármacos , Proteínas Bacterianas/ultraestructura , Microscopía por Crioelectrón , ARN Polimerasas Dirigidas por ADN/metabolismo , ARN Polimerasas Dirigidas por ADN/ultraestructura , Regiones Promotoras Genéticas/genética , Transactivadores/ultraestructura
13.
BMC Infect Dis ; 20(1): 950, 2020 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-33308173

RESUMEN

BACKGROUND: Antimicrobial resistance in M. genitalium is a growing clinical problem. We investigated the mutations associated with macrolide and fluoroquinolone resistance, two commonly used medical regimens for treatment in China. Our aim is to analyze the prevalence and diversity of mutations among M. genitalium-positive clinical specimens in Guangzhou, south China. METHODS: A total of 154 stored M. genitalium positive specimens from men and women attending a STI clinic were tested for macrolide and fluoroquinolone mutations. M. genitalium was detected via TaqMan MGB real-time PCR. Mutations associated with macrolide resistance were detected using primers targeting region V of the 23S rRNA gene. Fluoroquinolone resistant mutations were screened via primers targeting topoisomerase IV (parC) and DNA gyrase (gyrA). RESULTS: 98.7% (152/154), 95.5% (147/154) and 90.3% (139/154) of M. genitalium positive samples produced sufficient amplicon for detecting resistance mutations in 23S rRNA, gyrA and parC genes, respectively. 66.4% (101/152), 0.7% (1/147) and 77.7% (108/139) samples manifested mutations in 23S rRNA, gyrA and parC genes, respectively. A2072G (59/101, 58.4%) and S83I (79/108, 73.1%) were highly predominating in 23S rRNA and parC genes, respectively. Two samples had amino acid substitutions in gyrA (M95I and A96T, respectively). Two samples had two amino acid substitutions in parC (S83I + D87Y). 48.6% (67/138) of samples harbored both macrolide and fluoroquinolone resistance-associated mutations. The most common combination of mutations was A2072G (23S rRNA) and S83I (parC) (40/67, 59.7%). One sample had three amino acid changes in 23S rRNA, gyrA and parC genes (A2072G + A96T + S83I). CONCLUSIONS: The high antimicrobial resistance rate of M. genitalium in Guangzhou is a very worrying problem and suggests that antimicrobial resistance testing and the development of new antibiotic regimens are crucially needed.


Asunto(s)
Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/genética , Fluoroquinolonas/uso terapéutico , Macrólidos/uso terapéutico , Mutación , Infecciones por Mycoplasma/tratamiento farmacológico , Mycoplasma genitalium/genética , Enfermedades Bacterianas de Transmisión Sexual/tratamiento farmacológico , China/epidemiología , Girasa de ADN/genética , Topoisomerasa de ADN IV/genética , ADN Bacteriano/genética , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Femenino , Humanos , Masculino , Infecciones por Mycoplasma/epidemiología , Infecciones por Mycoplasma/microbiología , Mycoplasma genitalium/aislamiento & purificación , Prevalencia , ARN Ribosómico 23S/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Estudios Retrospectivos , Enfermedades Bacterianas de Transmisión Sexual/epidemiología , Enfermedades Bacterianas de Transmisión Sexual/microbiología
14.
BMC Infect Dis ; 20(1): 908, 2020 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-33256619

RESUMEN

BACKGROUND: Diarrhoea, affecting children in developing countries, is mainly caused by diarrheagenic Escherichia coli (DEC). This study principally aimed to determine the prevalence of DEC pathotypes and Extended-spectrum ß-lactamase (ESBL) genes isolated from children under 5 years old with diarrhea. METHODS: A total of 320 diarrhoea stool samples were investigated. E. coli isolates were investigated for genes specific for enterotoxigenic E. coli (ETEC), enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), enteroinvasive E. coli (EIEC) and enterohemorrhagic E. coli (EHEC) using polymerase chain reaction (PCR). Furthermore, antimicrobial susceptibility testing, detection of antibiotic resistance-genes and phylogenetic typing were performed. RESULTS: Over all, DEC were isolated from 66/320 (20.6%) of the children with diarrhoea. EAEC was the predominant (47%), followed by typical EPEC (28.8%) and atypical EPEC (16.6%). Co-infection by EPEC and EAEC was detected in (7.6%) of isolates. However, ETEC, EIEC and EHEC were not detected. Phylogroup A (47%) and B2 (43.9%) were the predominant types. Multidrug-resistance (MDR) was found in 55% of DEC isolates. Extended-spectrum ß-lactamase (ESBL) genes were detected in 24 isolates (24 blaTEM and 15 blaCTX-M-15). Only one isolate harbored AmpC ß-lactamase gene (DHA gene). CONCLUSION: The study concluded that, EAEC and EPEC are important causative agents of diarrhoea in children under 5 years. MDR among DEC has the potential to be a big concern.


Asunto(s)
Infecciones Comunitarias Adquiridas/diagnóstico , Diarrea/diagnóstico , Farmacorresistencia Bacteriana Múltiple/genética , Escherichia coli Enteropatógena/genética , Infecciones por Escherichia coli/diagnóstico , Escherichia coli/genética , Filogenia , Antibacterianos/uso terapéutico , Proteínas Bacterianas/genética , Preescolar , Estudios de Cohortes , Coinfección/diagnóstico , Coinfección/microbiología , Infecciones Comunitarias Adquiridas/tratamiento farmacológico , Infecciones Comunitarias Adquiridas/epidemiología , Infecciones Comunitarias Adquiridas/microbiología , Diarrea/tratamiento farmacológico , Diarrea/epidemiología , Diarrea/microbiología , Egipto/epidemiología , Escherichia coli Enteropatógena/enzimología , Escherichia coli Enteropatógena/aislamiento & purificación , Escherichia coli/enzimología , Escherichia coli/aislamiento & purificación , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/epidemiología , Infecciones por Escherichia coli/microbiología , Heces/microbiología , Femenino , Humanos , Lactante , Masculino , Pruebas de Sensibilidad Microbiana , Reacción en Cadena de la Polimerasa , Prevalencia , beta-Lactamasas/genética
15.
Rev Soc Bras Med Trop ; 54: e02622020, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33338110

RESUMEN

INTRODUCTION: Carbapenemase-resistant enterobacteria that produce the bla NDM gene are found worldwide. However, this is the first report of blaNDM in Klebsiella aerogenes in Brazil. METHODS: The identification of bacterial species was performed using anautomated system and confirmed by biochemical tests, 16S rRNA gene sequencing, and detection of resistance genes. RESULTS: The clinical isolate showed minimum inhibitory concentration resistance to meropenem and polymyxin B at 8mg/L and 4mg/L, respectively. Only the blaNDM gene was detected. CONCLUSIONS: The current report of the blaNDM gene in isolated MDR enterobacteria indicates that this gene can spread silently in a hospital setting.


Asunto(s)
Enterobacter aerogenes , Antibacterianos/farmacología , Proteínas Bacterianas , Brasil , Farmacorresistencia Bacteriana Múltiple/genética , Enterobacter aerogenes/genética , Enterobacteriaceae , Klebsiella pneumoniae/genética , Pruebas de Sensibilidad Microbiana , ARN Ribosómico 16S , beta-Lactamasas/genética
16.
Dis Aquat Organ ; 142: 119-124, 2020 Dec 03.
Artículo en Inglés | MEDLINE | ID: mdl-33269723

RESUMEN

An outbreak of salmonellosis occurred in a group of 7 long-nosed fur seals Arctocephalus forsteri undergoing rehabilitation after being found injured and malnourished on beaches along the northern New South Wales and southern Queensland coasts of Australia. Three of the 7 individuals developed clinical disease and died within 3 d. Clinical signs included profuse diarrhea, vomiting, depression, and lethargy. Salmonella enterica subsp. enterica serovar Kentucky (S. Kentucky) was cultured from 2 of the 3 deceased animals. The other 4 animals showed similar signs and recovered following treatment. S. Kentucky (antigenic formula 8,20:i:z6) was isolated from the survivors and tissues recovered from post-mortem samples of deceased animals. The bacterium was susceptible to cephalothin and sulfamethoxazole/trimethoprim and resistant to amoxicillin-clavulanate, ampicillin/amoxicillin, tetracycline, and enrofloxacin. This organism has the potential to cause disease in aquatic wildlife, as well as posing a zoonotic threat to people who utilise the aquatic environment.


Asunto(s)
Lobos Marinos , Animales , Antibacterianos/farmacología , Australia , Brotes de Enfermedades/veterinaria , Farmacorresistencia Bacteriana Múltiple , Kentucky/epidemiología , Pruebas de Sensibilidad Microbiana/veterinaria , Nueva Gales del Sur , Queensland , Salmonella
17.
J Ayub Med Coll Abbottabad ; 32(4): 459-464, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33225644

RESUMEN

BACKGROUND: The incidence of multidrug-resistant (MDR), extreme drug resistant (XDR), and pan drug-resistant (PDR) Acinetobacter are increasing throughout the world. The therapeutic management and control of Acinetobacter are difficult due to the emergence of drug resistance and its enduring capacity to survive in the environment. The present study was designed to appraise the efficacy of Polymyxins and Tigecycline against multidrugresistant Acinetobacter isolates from surgical and burn wounds. METHODS: During the study, the specimens were collected from various types of wounds from inpatients and outpatients of the tertiary care hospitals of Lahore, Pakistan in 2017 and 2018. The bacterial pathogens were isolated and identified using standard microbiological procedures and molecular confirmation of Acinetobacter species was examined by PCR using specific primers. The antibiotic susceptibility profiling of Acinetobacter isolates was studied against 18 antibiotics as per Clinical and Laboratory Standards Institute (CLSI) guidelines. RESULTS: The Acinetobacter isolates demonstrated extreme resistance especially to ampicillin/sulbactam, piperacillin/tazobactam, cephalosporins, carbapenems, fluoroquinolones, and aminoglycosides. However, the colistin, polymyxin, and tigecycline remained the most effective antimicrobial agents against Acinetobacter isolates. CONCLUSIONS: The results highlight the extent of drug resistance and therapeutic potential of Polymyxins and Tigecycline for wound infections caused by MDR and XDR Acinetobacter species. The wiser use of antimicrobials, incessant surveillance of antimicrobial resistance, and stringent adherence to infection control guidelines are critical to reducing major outbreaks in the future.


Asunto(s)
Acinetobacter/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple , Polimixinas/farmacología , Tigeciclina/farmacología , Infección de Heridas/microbiología , Infecciones por Acinetobacter/microbiología , Antibacterianos/farmacología , Humanos , Pruebas de Sensibilidad Microbiana , Pakistán
18.
PLoS One ; 15(11): e0242593, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33227031

RESUMEN

Bacterial efflux pumps are an important pathogenicity trait because they extrude a variety of xenobiotics. Our laboratory previously identified in silico Burkholderia collagen-like protein 8 (Bucl8) in the hazardous pathogens Burkholderia pseudomallei and Burkholderia mallei. We hypothesize that Bucl8, which contains two predicted tandem outer membrane efflux pump domains, is a component of a putative efflux pump. Unique to Bucl8, as compared to other outer membrane proteins, is the presence of an extended extracellular region containing a collagen-like (CL) domain and a non-collagenous C-terminus (Ct). Molecular modeling and circular dichroism spectroscopy with a recombinant protein, corresponding to this extracellular CL-Ct portion of Bucl8, demonstrated that it adopts a collagen triple helix, whereas functional assays screening for Bucl8 ligands identified binding to fibrinogen. Bioinformatic analysis of the bucl8 gene locus revealed it resembles a classical efflux-pump operon. The bucl8 gene is co-localized with downstream fusCDE genes encoding fusaric acid (FA) resistance, and with an upstream gene, designated as fusR, encoding a LysR-type transcriptional regulator. Using reverse transcriptase (RT)-qPCR, we defined the boundaries and transcriptional organization of the fusR-bucl8-fusCDE operon. We found exogenous FA induced bucl8 transcription over 80-fold in B. pseudomallei, while deletion of the entire bucl8 locus decreased the minimum inhibitory concentration of FA 4-fold in its isogenic mutant. We furthermore showed that the putative Bucl8-associated pump expressed in the heterologous Escherichia coli host confers FA resistance. On the contrary, the Bucl8-associated pump did not confer resistance to a panel of clinically-relevant antimicrobials in Burkholderia and E. coli. We finally demonstrated that deletion of the bucl8-locus drastically affects the growth of the mutant in L-broth. We determined that Bucl8 is a component of a novel tetrapartite efflux pump, which confers FA resistance, fibrinogen binding, and optimal growth.


Asunto(s)
Burkholderia mallei/metabolismo , Burkholderia pseudomallei/metabolismo , Proteínas de Transporte de Membrana/metabolismo , Proteínas de la Membrana Bacteriana Externa/metabolismo , Proteínas de la Membrana Bacteriana Externa/fisiología , Burkholderia/genética , Burkholderia/metabolismo , Burkholderia mallei/genética , Burkholderia pseudomallei/genética , Colágeno/metabolismo , Farmacorresistencia Bacteriana Múltiple/genética , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Genes Bacterianos/efectos de los fármacos , Operón/efectos de los fármacos , Factores de Transcripción/metabolismo
19.
PLoS One ; 15(11): e0242544, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33237921

RESUMEN

OBJECTIVES: Multidrug-resistant organisms (MDRO) are considered an emerging threat worldwide. Data covering the clinical impact of MDRO colonization in patients with solid malignancies, however, is widely missing. We sought to determine the impact of MDRO colonization in patients who have been diagnosed with Non-small cell lung cancer (NSCLC) who are at known high-risk for invasive infections. MATERIALS AND METHODS: Patients who were screened for MDRO colonization within a 90-day period after NSCLC diagnosis of all stages were included in this single-center retrospective study. RESULTS: Two hundred and ninety-five patients were included of whom 24 patients (8.1%) were screened positive for MDRO colonization (MDROpos) at first diagnosis. Enterobacterales were by far the most frequent MDRO detected with a proportion of 79.2% (19/24). MDRO colonization was present across all disease stages and more present in patients with concomitant diabetes mellitus. Median overall survival was significantly inferior in the MDROpos study group with a median OS of 7.8 months (95% CI, 0.0-19.9 months) compared to a median OS of 23.9 months (95% CI, 17.6-30.1 months) in the MDROneg group in univariate (p = 0.036) and multivariate analysis (P = 0.02). Exploratory analyses suggest a higher rate of non-cancer-related-mortality in MDROpos patients compared to MDROneg patients (p = 0.002) with an increased rate of fatal infections in MDROpos patients (p = 0.0002). CONCLUSIONS: MDRO colonization is an independent risk factor for inferior OS in patients diagnosed with NSCLC due to a higher rate of fatal infections. Empirical antibiotic treatment approaches should cover formerly detected MDR commensals in cases of (suspected) invasive infections.


Asunto(s)
Bacterias/aislamiento & purificación , Carcinoma de Pulmón de Células no Pequeñas/microbiología , Farmacorresistencia Bacteriana Múltiple , Neoplasias Pulmonares/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Bacterias/efectos de los fármacos , Infecciones Bacterianas/complicaciones , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/terapia , Causas de Muerte , Comorbilidad , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/terapia , Masculino , Persona de Mediana Edad , Nariz/microbiología , Admisión del Paciente/estadística & datos numéricos , Faringe/microbiología , Recto/microbiología , Estudios Retrospectivos , Factores de Riesgo
20.
Medicine (Baltimore) ; 99(45): e23169, 2020 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-33158003

RESUMEN

Bacterial infection has been identified as one of the most significant complications of liver transplantation (LT). Multidrug-resistant (MDR) gram-negative bacteria (GNB) infection remains problematic issue following LT in the adults. However, data in children are scarce. We aimed to examine the prevalence and associated factors of MDR-GNB infection among pediatric LT recipients.We performed a single-center retrospectively study of 118 children who underwent LT between January 2010 and December 2018. Data on the prevalence, clinical characteristics, types, and sites of MDR-GNB infection within 3 months after LT as well as the treatment outcomes were collected. Multidrug resistance was defined as acquired non-susceptibility to at least 1 agent in 3 or more antibiotic classes.In total, 64 (53.7%) patients developed 96 episodes of culture-proven bacterial infection with 93 GNB isolates. Moreover, there were 58 (62.4%) MDR-GNB isolates, with a predominance of Klebsiella pneumoniae (32.7%), Escherichia coli (31%), and Pseudomonas aeruginosa (10.3%). Interestingly, 10 (17.2%) isolates were determined to be carbapenem-resistant Enterobacteriaceae. The median time to MDR-GNB infection was 9 (interquartile range: 5-33) days. The most common type of infection was intra-abdominal infection (47.9%). In the multivariate analysis, the significant variables associated with post-LT MDR-GNB infection include exposure to third-generation cephalosporins (hazard ratio [HR]: 2.16, P = .023), operative time (hazard ratio [HR] 1.20, P = .009), and length of intensive care unit stay (HR 1.03, P = .049). With a focus on carbapenem-resistant Enterobacteriaceae infection, a pediatric end-stage liver disease score >21 was the only significant 6 variable in the multivariate analysis (HR 11.48, P = .024). The overall 3-month mortality rate was 6.8%.This study has highlighted the high prevalence rate of MDR-GNB infection after pediatric LT. Therefore, caution on the emergence of MDR-GNB infection should be paid in at-risk children. Moreover, knowledge regarding the prevalence of MDR-GNB infection and resistant patterns is essential for guideline development to prevent and minimize the risk of MDR-GNB infection in this group of patients.


Asunto(s)
Farmacorresistencia Bacteriana Múltiple , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Gramnegativas/microbiología , Trasplante de Hígado , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/microbiología , Preescolar , Femenino , Humanos , Lactante , Masculino , Prevalencia , Estudios Retrospectivos , Factores de Riesgo
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