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1.
Food Chem ; 334: 127603, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-32712492

RESUMEN

Present work comprises the use of different solid-state Nuclear Magnetic Resonance strategies for characterizing structural and motional aspects of the peptide matrix that compose a set of four lyophilized Mexican cheese aqueous soluble extracts, each with a controlled ripening. Heteronuclear dipolar coupling modulation schemes allowed to characterize local mobility and structural homogeneity of cheeses' peptide segments in the solid-state as a function of ripening. Results suggest that ripened samples with certain local flexibility but important structural homogeneity present efficient microbial inhibition against tested bacterial strains, whilst high local rigidity of peptides within ripened cheese soluble fractions could partially explain the observed lack of antimicrobial activity. The present study attempts to propose novel observables for lyophilized cheese water soluble extracts that could be partially associated to their ripening-dependent antimicrobial activities, whereas said observables shall contribute to the better targeting, design and optimization of solid-state natural food bio-preservatives.


Asunto(s)
Antiinfecciosos/química , Antiinfecciosos/farmacología , Queso , Espectroscopía de Resonancia Magnética/métodos , Antiinfecciosos/análisis , Isótopos de Carbono , Queso/análisis , Liofilización , Pruebas de Sensibilidad Microbiana , Péptidos/análisis , Péptidos/química , Péptidos/farmacología , Solubilidad , Agua
2.
Food Chem ; 336: 127669, 2021 Jan 30.
Artículo en Inglés | MEDLINE | ID: mdl-32758804

RESUMEN

Curcumin was recently attracted great interest owing to its multiple bioactivities; however, the use of curcumin was hindered by its poor solubility and stability. In this study, curcumin-nisin-soy soluble polysaccharide nanoparticles (Cur-Nisin-SSPS-NPs, size = 118.76 nm) have been successfully elaborated to improve the application of curcumin. The formation of Cur-Nisin-SSPS-NPs was mediated by amphiphilic and positively charged nisin: SSPS encapsulated nisin, which was mainly driven by electrostatic attraction. And nisin-SSPS complex encapsulated curcumin mainly through hydrophobic interactions between nisin and curcumin. The encapsulation efficiency of curcumin (91.66%) in this novel nanocarriers was significantly higher than that in nanoparticles prepared by a single SSPS (31.82%) or nisin (41.69%), most likely because more hydrophobic regions of nisin were exposed after interacting with SSPS through electrostatic interaction. Consequently, this facile and green nanocarriers improved the solubility/dispersibility and stability of curcumin and nisin, as well as endowed SSPS-based nanoparticles with antioxidant and antimicrobial activities.


Asunto(s)
Curcumina/administración & dosificación , Portadores de Fármacos/química , Nanopartículas/química , Nisina/química , Polisacáridos/química , Antibacterianos/administración & dosificación , Antibacterianos/química , Antibacterianos/farmacología , Antioxidantes/química , Antioxidantes/farmacología , Curcumina/química , Curcumina/farmacocinética , Liberación de Fármacos , Interacciones Hidrofóbicas e Hidrofílicas , Imidazoles , Pruebas de Sensibilidad Microbiana , Microscopía Electrónica de Transmisión , Morfolinas , Solubilidad , Soja/química , Espectrofotometría Ultravioleta
3.
Sci Total Environ ; 751: 142217, 2021 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-33181985

RESUMEN

Global use of antibiotics has exceedingly enhanced in agricultural, veterinary and prophylactic human use in recent days. Hence, these antibiotics can easily be found in the environment. This study revealed the occurrence of emerging MDR and ESBL producing strains, pollution profile, and factors integrons (intI1 and intI2) and environmental factors associated, in the riverine systems under different ecological and geo-climatic zones were investigated. The samples were collected based on anthropogenic intervention such as discharge of domestic wastes, industrial wastes, hospital, and municipal wastes. Among 160bacterial morphotypes, 121 (75.62%) exhibited MDR trait with maximum resistance towards lincosamide (CD = 71.3%), beta-lactams (P = 70.6%; AMX = 66.3%), cephalosporin (CZ = 60.6%; CXM = 34.4%), sulfonamide (COT = 50.6%; TR = 43.8%) followed by macrolide (E = 29.4%), tetracycline (TET = 18.8%), aminoglycosides (S = 18.8%; GEN = 6.3%), fluoroquinolones (NX = 18.1%; OF = 4.4%) and carbapenem (IPM = 5.0%). IntI1 gene was detected in 73 (60.3%) of isolates, whereas intI2 was found in 11 (9.09%) isolates. Eight (6.61%) isolates carried both integron genes (intI1 and intI2). sul1 and dfrA1 genes were detected in 53 (72.6%) and 63 (86.3%) isolates, respectively. A total of 103 (85.1%) were found ESBL positive with the presence of ESBL genes in 100 (97.08%) isolates. In riverine systems most prevalent ESBL gene blaTEM (93.0%) was detected alone as well as in combination with bla genes. The data can be utilized for public awareness and regulation of guidelines by local governing bodies as an alarming threat to look-out against the prevalent resistance in environment thereby assisting in risk management during epidemics. This study is a comprehensive investigation of emerging antibiotic pollutants and its resistance in bacteria associated with factors integrons-integrase responsible for its dissemination. It may also assist in global surveillance of antibiotic resistance and policies to curtail unnecessary antibiotic use.


Asunto(s)
Integrasas , Integrones , Antibacterianos , Humanos , Pruebas de Sensibilidad Microbiana , Sulfonamidas
4.
Sci Total Environ ; 750: 142265, 2021 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-33182186

RESUMEN

The emergence of antibiotic-resistant clinically relevant facultative pathogenic bacteria in the environment has become one of the most important global health challenges. Antibiotic-resistant bacteria (ARB) have been found in surface waters and wastewater treatment plants. Drinking water guidelines and the EU bathing water directive 2006/7/EC include the surveillance of defined microbiological parameters on species level, while the monitoring of ARB is missing in all existing guidelines. However, standardized methods for the detection of ARB exist for clinical investigations of human materials only. They are based on cultivation on selective agar plates. These methods cannot be used directly for environmental samples, because of the high amount and diversity of bacterial background flora which interferes with the detection of human-relevant ARB. The aim of this study was to introduce a proposal for future normative standard operation procedures, with international relevance, for the culture-based detection of clinically-relevant antibiotic resistant bacteria in aquatic environmental samples like wastewater and surface water: gram-negative bacteria resistant against 3rd generation cephalosporins (ESBL) and against carbapenems (CARBA), gram-positive vancomycin-resistant enterococci (VRE) and methicillin-resistant Staphylococcus aureus (MRSA). The final adaptation of standardized cultivation methods included increasing the standard incubation temperature from 36 °C to 42 °C, which effectively inhibits the environmental background flora on agar plates while the desired target species survive. This enables the detection of target species in suitable sample volumes. Putative target colonies which belong to the remaining background flora had to be excluded by morphological and physiological differentiation. Therefore, a time and cost optimized testing scheme with good performance was developed, which allows an effective exclusion of non-target isolates in samples. Depending on the target species and sample type, sensitivity of up to 100% is achieved, and specificity ranges from 91.1% to 99.7%, while the positive predictive value, negative predicted value and accuracy rate are always >90%.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Enterococos Resistentes a la Vancomicina , Antagonistas de Receptores de Angiotensina , Inhibidores de la Enzima Convertidora de Angiotensina , Antibacterianos , Humanos , Pruebas de Sensibilidad Microbiana
5.
Braz Dent J ; 31(5): 485-492, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33146331

RESUMEN

Green chemistry has been applied in different areas due to the growing demands for renewable processes and one of them is nanotechnology. The aim of this study was to characterize a formulation containing silver nanoparticles (AgNPs) produced by a green synthesis and to evaluate its antimicrobial activity. The formulation will be used as an intracanal dressing exploiting the AgNPs' antimicrobial properties, which are crucial to prevent infections and bacterial reinfections that can compromise endodontic treatments. In the green synthesis, silver nitrate was employed as the precursor salt, maltose as a reducing agent, and gelatin as a stabilizing agent. The formulation was prepared mixing 50 % of a liquid containing the AgNPs and 50 % of hydroxyethylcellulose gel at 1.5 % with proper evaluation of the process inherent parameters. Techniques such as molecular absorption spectrometry and dynamic light scattering were used in characterization step. The antimicrobial activity of the AgNPs against Escherichia coli ATCC 25922, Enterococcus faecalis NCTC 775, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923 and Streptococcus mutans ATCC 25175 was verified according to National Comittee for Clinical Laboratory Standards (NCCLS) by determining minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). The obtained results indicated the formulation containing AgNPs produced by a green synthesis was properly characterized by the selected techniques. Furthermore, the formulation assessment proved that it is suitable for the proposal as well as it has potential to be used as an intracanal dressing since presented antimicrobial activity against all bacterial strains evaluated.


Asunto(s)
Antiinfecciosos , Nanopartículas del Metal , Antibacterianos/farmacología , Antiinfecciosos/farmacología , Vendajes , Pruebas de Sensibilidad Microbiana , Plata/farmacología
6.
Georgian Med News ; (306): 142-146, 2020 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33130662

RESUMEN

The objective of the study was to assess antibacterial activity of antibiotic-impregnated bone allograft processed according to the Marburg bone bank system. In the experiment, thermal processed bone allografts according to the Marburg bone bank system were used. They were impregnated with gentamicin. Four groups are formed depending on the impregnation method. In I and II groups, an entire femoral heads and, in III and IV perforated femoral heads were used. In groups I and III, antibiotic impregnation was carried out simultaneously with the thermal disinfection, and in groups II and IV after thermal disinfection. In the control group, the bone allografts were heat treated, then impregnated with saline. The antibiotic release was evaluated by agar diffusion test against Staphylococcus aureus, Pseudomonas aeruginosa and Klebsiella pneumonia. The results of the study indicate the presence of antimicrobial activity against S. aureus, P. aeruginosa and K. pneumonia in all groups except the control group. However, in the II and IV group, the inhibition zone was higher compared with the I and III groups (p<0.05). We conclude that the capacity of bone allografts processed according to the Marburg bone bank system to act as gentamicin carriers has been confirmed in this study. Gentamycin loaded perforated bone allograft (IV group) showed statistically higher efficacy against S. aureus, P. aeruginosa and K. pneumonia among studied groups.


Asunto(s)
Antibacterianos , Staphylococcus aureus , Aloinjertos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Gentamicinas/farmacología , Calor , Pruebas de Sensibilidad Microbiana
7.
BMC Infect Dis ; 20(1): 809, 2020 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-33153450

RESUMEN

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.


Asunto(s)
Antibacterianos/uso terapéutico , Azitromicina/uso terapéutico , Ceftriaxona/uso terapéutico , Farmacorresistencia Bacteriana/efectos de los fármacos , Gonorrea/tratamiento farmacológico , Neisseria gonorrhoeae/efectos de los fármacos , Adolescente , Adulto , Anciano , Femenino , Gonorrea/epidemiología , Gonorrea/microbiología , Humanos , Laboratorios , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Neisseria gonorrhoeae/aislamiento & purificación , Vietnam/epidemiología , Adulto Joven
8.
BMC Infect Dis ; 20(1): 816, 2020 Nov 10.
Artículo en Inglés | MEDLINE | ID: mdl-33167886

RESUMEN

BACKGROUND: The prevalence of Staphylococcus aureus varies depending on the healthcare facility, region and country. To understand its genetic diversity, transmission, dissemination, epidemiology and evolution in a particular geographical location, it is important to understand the similarities and variations in the population being studied. This can be achieved by using various molecular characterisation techniques. This study aimed to provide detailed molecular characterisation of South African mecA-positive S. aureus blood culture isolates by describing the SCCmec types, spa types and to lesser extent, the sequence types obtained from two consecutive national surveillance studies. METHODS: S. aureus blood culture isolates from a national laboratory-based and enhanced surveillance programme were identified and antimicrobial susceptibility testing was performed using automated systems. A real-time PCR assay confirmed the presence of the methicillin-resistance determinant, mecA. Conventional PCR assays were used to identify the SCCmec type and spa type, which was subsequently analysed using the Ridom StaphType™ software. Multilocus sequence typing was performed on selected isolates using conventional methods. MRSA clones were defined by their sequence type (ST), SCCmec type and spa type. RESULTS: A detailed description of findings is reported in this manuscript. SCCmec type III predominated overall followed by type IV. A total of 71 different spa types and 24 novel spa types were observed. Spa type t037 was the most common and predominated throughout followed by t1257. Isolates were multidrug resistant; isolates belonging to all SCCmec types were resistant to most of the antibiotics with the exception of type I; isolates with spa type t045 showed resistance to all antibiotics except vancomycin. The most diverse SCCmec-spa type complex was composed of the SCCmec type IV element and 53 different spa types. CONCLUSION: Although ST data was limited, thereby limiting the number of clones that could be identified, the circulating clones were relatively diverse.


Asunto(s)
Proteínas Bacterianas/genética , Variación Genética , Secuencias Repetitivas Esparcidas/genética , Staphylococcus aureus Resistente a Meticilina/genética , Proteínas de Unión a las Penicilinas/genética , Infecciones Estafilocócicas/epidemiología , Proteína Estafilocócica A/genética , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Proteínas Bacterianas/sangre , Cultivo de Sangre , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/genética , Humanos , Meticilina/farmacología , Meticilina/uso terapéutico , Resistencia a la Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Proteínas de Unión a las Penicilinas/sangre , Reacción en Cadena en Tiempo Real de la Polimerasa , Sudáfrica/epidemiología , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Vancomicina/farmacología , Vancomicina/uso terapéutico
9.
BMC Infect Dis ; 20(1): 833, 2020 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-33176714

RESUMEN

BACKGROUND: Alcaligenes faecalis is usually causes opportunistic infections in humans. Alcaligenes faecalis infection is often difficult to treat due to its increased resistance to several antibiotics. The results from a clinical study of patients with Alcaligenes faecalis infection may help improve patients' clinical care. METHODS: We conducted a retrospective analysis of all patients presenting with Alcaligenes faecalis infection from January 2014 to December 2019. The medical records of all patients were reviewed for demographic information, clinical symptoms and signs, comorbidities, use of intravenous antibiotics within the past three months, bacterial culture, antibiotics sensitivity test, and clinical outcomes. RESULTS: Sixty-one cases of Alcaligenes faecalis infection were seen during the study period, including 25 cases of cystitis, nine cases of diabetic foot infection, eight cases of pneumonia, seven cases of acute pyelonephritis, three cases of bacteremia, and nine cases of infection at specific sites. Thirty-seven patients (60.7%) had a history of receiving intravenous antibiotics within three months of the diagnosis. Fifty-one (83.6%) cases were mixed with other bacterial infections. Extensively drug-resistant infections have been reported since 2018. The best sensitivity rate to Alcaligenes faecalis was 66.7% for three antibiotics (imipenem, meropenem, and ceftazidime) in 2019. Two antibiotics (ciprofloxacin and piperacillin/tazobactam) sensitivity rates to A. faecalis were less than 50%. CONCLUSIONS: The most frequent Alcaligenes faecalis infection sites, in order, are the bloodstream, urinary tract, skin and soft tissue, and middle ear. The susceptibility rate of Alcaligenes faecalis to commonly used antibiotics is decreasing. Extensively drug-resistant Alcaligenes faecalis infections have emerged.


Asunto(s)
Alcaligenes faecalis/efectos de los fármacos , Antibacterianos/uso terapéutico , Ceftazidima/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Imipenem/uso terapéutico , Meropenem/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Alcaligenes faecalis/genética , Alcaligenes faecalis/aislamiento & purificación , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Femenino , Infecciones por Bacterias Gramnegativas/microbiología , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento
10.
Molecules ; 25(21)2020 Oct 31.
Artículo en Inglés | MEDLINE | ID: mdl-33142770

RESUMEN

In December 2019, a new severe acute respiratory syndrome coronavirus (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), emerged in Wuhan, China. Despite containment measures, SARS-CoV-2 spread in Asia, Southern Europe, then in America and currently in Africa. Identifying effective antiviral drugs is urgently needed. An efficient approach to drug discovery is to evaluate whether existing approved drugs can be efficient against SARS-CoV-2. Doxycycline, which is a second-generation tetracycline with broad-spectrum antimicrobial, antimalarial and anti-inflammatory activities, showed in vitro activity on Vero E6 cells infected with a clinically isolated SARS-CoV-2 strain (IHUMI-3) with median effective concentration (EC50) of 4.5 ± 2.9 µM, compatible with oral uptake and intravenous administrations. Doxycycline interacted both on SARS-CoV-2 entry and in replication after virus entry. Besides its in vitro antiviral activity against SARS-CoV-2, doxycycline has anti-inflammatory effects by decreasing the expression of various pro-inflammatory cytokines and could prevent co-infections and superinfections due to broad-spectrum antimicrobial activity. Therefore, doxycycline could be a potential partner of COVID-19 therapies. However, these results must be taken with caution regarding the potential use in SARS-CoV-2-infected patients: it is difficult to translate in vitro study results to actual clinical treatment in patients. In vivo evaluation in animal experimental models is required to confirm the antiviral effects of doxycycline on SARS-CoV-2 and more trials of high-risk patients with moderate to severe COVID-19 infections must be initiated.


Asunto(s)
Antivirales/farmacología , Betacoronavirus/efectos de los fármacos , Doxiciclina/farmacología , Animales , Antibacterianos/farmacología , Antiinflamatorios no Esteroideos/uso terapéutico , Chlorocebus aethiops , Cloroquina/farmacología , Técnicas In Vitro , Pruebas de Sensibilidad Microbiana , Células Vero
11.
Urologiia ; (5): 116-120, 2020 Nov.
Artículo en Ruso | MEDLINE | ID: mdl-33185358

RESUMEN

The choice of antimicrobials for the treatment of urinary tract infections (UTIs) is determined by many factors, however, at present, population antibiotic resistance of uropathogens is used as one of the most important criteria. At the same time, there are cases when the clinical efficacy of an antimicrobial drug does not correlate with in vitro activity, in particular, such discordance was found for fosfomycin trometamol. Comparison of data from microbiological studies of UTI pathogens performed at different times is of great practical and scientific interest. At the same time, such comparisons have limitations, such as the use of different criteria for interpreting the sensitivity of microorganisms, the peculiarities of the formation of the studied patient population, and collection of strains in different geographical areas. Therefore, for all the seeming simplicity and clarity of the data on the sensitivity of uropathogens, their use to substantiate rational antimicrobial therapy is associated with numerous nuances that can significantly distort their objective assessment. In this connection, it is important to conduct not only microbiological, but also clinical studies to obtain data on the comparative effectiveness of the antimicrobials used.


Asunto(s)
Fosfomicina , Infecciones Urinarias , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Farmacorresistencia Microbiana , Humanos , Pruebas de Sensibilidad Microbiana , Federación de Rusia , Infecciones Urinarias/tratamiento farmacológico
12.
BMC Infect Dis ; 20(1): 729, 2020 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-33028225

RESUMEN

BACKGROUND: This study describes the disease burden, clinical characteristics, antibiotic management, impact of multidrug resistance and outcome of Pseudomonas aeruginosa bloodstream infection (PABSI) among children admitted to a tertiary referral hospital for children in Cape Town, South Africa. METHODS: A retrospective descriptive study was conducted at a paediatric referral hospital in Cape Town, South Africa. Demographic and clinical details, antibiotic management and patient outcome information were extracted from medical and laboratory records. Antibiotic susceptibility results of identified organisms were obtained from the National Health Laboratory Service database. RESULTS: The incidence risk of PABSI was 5.4 (95% CI: 4.34-6.54) PABSI episodes / 10,000 hospital admissions and the most common presenting feature was respiratory distress, 34/91 (37.4%). Overall, 69/91 (75.8%) of the PA isolates were susceptible to all antipseudomonal antibiotic classes evaluated. Fifty (54.9%) of the PABSI episodes were treated with appropriate empiric antibiotic therapy. The mortality rate was 24.2% and in multivariable analysis, empiric antibiotic therapy to which PA isolates were not susceptible, infections present on admission, and not being in the intensive care unit at the time that PABSI was diagnosed were significantly associated with 14-day mortality. CONCLUSIONS: PABSI caused appreciable mortality, however, appropriate empiric antibiotic therapy was associated with reduced 14-day mortality.


Asunto(s)
Infecciones por Pseudomonas/diagnóstico , Pseudomonas aeruginosa/aislamiento & purificación , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Niño , Preescolar , Farmacorresistencia Bacteriana/efectos de los fármacos , Femenino , Hospitales Pediátricos , Humanos , Lactante , Unidades de Cuidados Intensivos , Masculino , Pruebas de Sensibilidad Microbiana , Infecciones por Pseudomonas/tratamiento farmacológico , Infecciones por Pseudomonas/mortalidad , Pseudomonas aeruginosa/efectos de los fármacos , Estudios Retrospectivos , Sudáfrica/epidemiología , Tasa de Supervivencia , Centros de Atención Terciaria
13.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(9): 1068-1073, 2020.
Artículo en Inglés, Chino | MEDLINE | ID: mdl-33051420

RESUMEN

OBJECTIVES: To analyze the pathogenic distribution, antibiotic susceptibility and prognostic factors for acute leukemia (AL) patients with Gram negative (G-) bacterial bloodstream infection (BSI), in order to provide theoretical basis for reducing the infection-related mortality of AL patients. METHODS: The clinical data of 1 055 AL patients with BSI admitted to the hematology ward of three large-scale hospitals in Hunan Province from January 2010 to December 2018 were collected. The etiology, antibiotic susceptibility data and clinical features of patients with G- bacterial infection were analyzed. RESULTS: G- bacterial infection accounted for 622 AL patients with BSI, and the main pathogens were Escherichia coli (277 strains, 44.53%), Klebsiella pneumoniae (138 strains, 22.19%), and Pseudomonas aeruginosa (81 strains, 13.02%). Most G- bacteria were highly sensitive to carbapenems and ß-lactam/ß-lactamase inhibitor. State of disease, Pitt score ≥4, treatment with vasoactive agents and sensitive antibiotic >48 h were independent risk factors of 30-day mortality. CONCLUSIONS: Rational antibacterial treatment of G- bacterial BSI in AL patients requires adequate acquaintance of the local pathogenic epidemiology and antibiotic susceptibility-monitored data. Broad-spectrum antibiotics covering the most common and more virulent pathogens should be timely applicated and adjusted according to antibiotic susceptibility results and efficacy.


Asunto(s)
Bacteriemia , Farmacorresistencia Bacteriana , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacteriemia/tratamiento farmacológico , Bacteriemia/epidemiología , Humanos , Pruebas de Sensibilidad Microbiana , Pronóstico
14.
Nat Commun ; 11(1): 4935, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-33004797

RESUMEN

Gramicidin A (1) is a peptide antibiotic that disrupts the transmembrane ion concentration gradient by forming an ion channel in a lipid bilayer. Although long used clinically, it is limited to topical application because of its strong hemolytic activity and mammalian cytotoxicity, likely arising from the common ion transport mechanism. Here we report an integrated high-throughput strategy for discovering analogues of 1 with altered biological activity profiles. The 4096 analogue structures are designed to maintain the charge-neutral, hydrophobic, and channel forming properties of 1. Synthesis of the analogues, tandem mass spectrometry sequencing, and 3 microscale screenings enable us to identify 10 representative analogues. Re-synthesis and detailed functional evaluations find that all 10 analogues share a similar ion channel function, but have different cytotoxic, hemolytic, and antibacterial activities. Our large-scale structure-activity relationship studies reveal the feasibility of developing analogues of 1 that selectively induce toxicity toward target organisms.


Asunto(s)
Antibacterianos/farmacología , Descubrimiento de Drogas/métodos , Gramicidina/análogos & derivados , Ensayos Analíticos de Alto Rendimiento/métodos , Animales , Antibacterianos/química , Línea Celular Tumoral , Química Farmacéutica , Eritrocitos , Estudios de Factibilidad , Bacterias Grampositivas/efectos de los fármacos , Gramicidina/química , Gramicidina/farmacología , Hemólisis/efectos de los fármacos , Concentración 50 Inhibidora , Ratones , Pruebas de Sensibilidad Microbiana , Estructura Molecular , Conejos , Relación Estructura-Actividad , Espectrometría de Masas en Tándem
15.
Nat Commun ; 11(1): 4915, 2020 10 01.
Artículo en Inglés | MEDLINE | ID: mdl-33004811

RESUMEN

A phenotype of Escherichia coli and Klebsiella pneumoniae, resistant to piperacillin/tazobactam (TZP) but susceptible to carbapenems and 3rd generation cephalosporins, has emerged. The resistance mechanism associated with this phenotype has been identified as hyperproduction of the ß-lactamase TEM. However, the mechanism of hyperproduction due to gene amplification is not well understood. Here, we report a mechanism of gene amplification due to a translocatable unit (TU) excising from an IS26-flanked pseudo-compound transposon, PTn6762, which harbours blaTEM-1B. The TU re-inserts into the chromosome adjacent to IS26 and forms a tandem array of TUs, which increases the copy number of blaTEM-1B, leading to TEM-1B hyperproduction and TZP resistance. Despite a significant increase in blaTEM-1B copy number, the TZP-resistant isolate does not incur a fitness cost compared to the TZP-susceptible ancestor. This mechanism of amplification of blaTEM-1B is an important consideration when using genomic data to predict susceptibility to TZP.


Asunto(s)
Antibacterianos/farmacología , Farmacorresistencia Bacteriana Múltiple/genética , Infecciones por Escherichia coli/tratamiento farmacológico , Proteínas de Escherichia coli/genética , Escherichia coli/genética , beta-Lactamasas/genética , Antibacterianos/uso terapéutico , Cromosomas Bacterianos/genética , Elementos Transponibles de ADN/genética , ADN Bacteriano/genética , Quimioterapia Combinada/métodos , Escherichia coli/efectos de los fármacos , Escherichia coli/aislamiento & purificación , Infecciones por Escherichia coli/microbiología , Amplificación de Genes , Regulación Bacteriana de la Expresión Génica , Genoma Bacteriano/genética , Humanos , Pruebas de Sensibilidad Microbiana , Piperacilina/farmacología , Piperacilina/uso terapéutico , Polimorfismo de Longitud del Fragmento de Restricción , ARN Ribosómico 16S/genética , Tazobactam/farmacología , Tazobactam/uso terapéutico , Secuenciación Completa del Genoma
16.
Annu Int Conf IEEE Eng Med Biol Soc ; 2020: 5880-5883, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-33019312

RESUMEN

Antibiotic resistant bacterial infections are a growing global health crisis. Antibiograms, aggregate antimicrobial resistance reports, are critical for tracking antibiotic susceptibility and prescribing antibiotics. This research leverages fifteen years of the expansive Massachusetts statewide antibiogram dataset curated by the Massachusetts Department of Public Health. Given the lengthy annual antibiogram creation process, data are not timely. Our prior research involved forecasting the current antimicrobial susceptibility given historic antibiograms. The objective for this research is to expand upon this prior work by identifying which antibiotic-bacteria combinations have resistance trends that are not well forecasted. For that, our proposed Previous Year Anomalous Trend Identification (PYATI) strategy employs a cluster driven outlier detection solution to identify the trends to remove before forecasting. Employing PYATI to remove antibiotic-bacteria combinations with anomalous trends statistically significantly reduces the forecasting error for the remaining combinations. As antibiotic resistance is furthered by prescribing ineffective antibiotics, PYATI can be leveraged to improve antibiotic prescribing.


Asunto(s)
Antibacterianos , Bacterias , Antibacterianos/uso terapéutico , Farmacorresistencia Microbiana , Massachusetts , Pruebas de Sensibilidad Microbiana
17.
BMC Infect Dis ; 20(1): 767, 2020 Oct 17.
Artículo en Inglés | MEDLINE | ID: mdl-33069221

RESUMEN

BACKGROUND: Ureaplasma urealyticum is an intra-cellular bacterium frequently found colonizing the genital tract. Known complications include localized infections, which can result in premature deliveries. Septic arthritis due to U. urealyticum in healthy patients is exceptionally rare, although opportunistic septic arthritis in agammaglobulinemic patients have been reported. However, there are no reports of septic arthritis due to U. urealyticum following caesarean section or in the post-partum period. CASE PRESENTATION: A 38-year-old immunocompetent woman presented with severe right shoulder pain, 1 month following emergency caesarean section at 26 weeks of gestation for pre-eclampsia and spontaneous placental disruption with an uncomplicated post-operative recovery. Our suspicion of septic arthritis was confirmed with abundant pus following arthrotomy by a delto-pectoral approach. Awaiting culture results, empirical antibiotic treatment with intravenous amoxicilline and clavulanic acid was initiated. In spite of sterile cultures, clinical evolution was unfavorable with persistent pain, inflammation and purulent drainage, requiring two additional surgical débridement and lavage procedures. The 16S ribosomal RNA PCR of the purulent liquid was positive for U. urealyticum at 2.95 × 106 copies/ml, specific cultures inoculated a posteriori were positive for U. urealyticum. Levofloxacin and azithromycine antibiotherapy was initiated. Susceptibility testing showed an intermediate sensibility to ciprofloxacin and clarithromycin. The strain was susceptible to doxycycline. Following cessation of breastfeeding, we started antibiotic treatment with doxycycline for 4 weeks. The subsequent course was favorable with an excellent functional and biological outcome. CONCLUSIONS: We report the first case of septic arthritis due to U. urealyticum after caesarean section. We hypothesize that the breach of the genital mucosal barrier during the caesarean section led to hematogenous spread resulting in purulent septic arthritis. The initial beta-lactam based antibiotic treatment, initiated for a purulent arthritis, did not provide coverage for cell wall deficient organisms. Detection of 16S rRNA allowed for a correct microbiological diagnosis in a patient with an unexpected clinical course.


Asunto(s)
Artritis Infecciosa/microbiología , Cesárea/efectos adversos , Hombro/microbiología , Infecciones por Ureaplasma/diagnóstico , Ureaplasma urealyticum/genética , Adulto , Antibacterianos/uso terapéutico , Artritis Infecciosa/tratamiento farmacológico , Doxiciclina/uso terapéutico , Femenino , Humanos , Pruebas de Sensibilidad Microbiana , Embarazo , Nacimiento Prematuro , ARN Ribosómico 16S/genética , Resultado del Tratamiento , Infecciones por Ureaplasma/tratamiento farmacológico , Infecciones por Ureaplasma/microbiología , Ureaplasma urealyticum/aislamiento & purificación , Sistema Urogenital/microbiología
18.
An Acad Bras Cienc ; 92(suppl 2): e20201216, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33084762

RESUMEN

Staphylococcus aureus (S. aureus) is a highly versatile Gram-positive bacterium that is carried asymptomatically by up to 30% of healthy people, while being a major cause of healthcare-associated infections, making it a worldwide problem in clinical medicine. The adaptive evolution of S. aureus strains is demonstrated by its remarkable capacity to promptly develop high resistance to multiple antibiotics, thus limiting treatment choice. Nowadays, there is a continuous demand for an alternative to the use of antibiotics for S. aureus infections and a strategy to control the spread or to kill phylogenetically related strains. In this scenario, bacteriocins fit as with a promising and interesting alternative. These molecules are produced by a range of bacteria, defined as ribosomally synthesized peptides with bacteriostatic or bactericidal activity against a wide range of pathogens. This work reviews ascertained the main antibiotic-resistance mechanisms of S. aureus strains and the current, informative content concerning the applicability of the use of bacteriocins overlapping the use of conventional antibiotics in the context of S. aureus infections. Besides, we highlight the possible application of these biomolecules on an industrial scale in future work.


Asunto(s)
Bacteriocinas , Infecciones Estafilocócicas , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacterias Grampositivas , Humanos , Pruebas de Sensibilidad Microbiana , Infecciones Estafilocócicas/tratamiento farmacológico , Staphylococcus aureus
19.
Nat Commun ; 11(1): 5328, 2020 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-33087704

RESUMEN

There is an urgent need to develop simple and fast antimicrobial susceptibility tests (ASTs) that allow informed prescribing of antibiotics. Here, we describe a label-free AST that can deliver results within an hour, using an actively dividing culture as starting material. The bacteria are incubated in the presence of an antibiotic for 30 min, and then approximately 105 cells are analysed one-by-one with microfluidic impedance cytometry for 2-3 min. The measured electrical characteristics reflect the phenotypic response of the bacteria to the mode of action of a particular antibiotic, in a 30-minute incubation window. The results are consistent with those obtained by classical broth microdilution assays for a range of antibiotics and bacterial species.


Asunto(s)
Pruebas de Sensibilidad Microbiana/métodos , Bacterias/química , Bacterias/efectos de los fármacos , Fenómenos Biofísicos , Farmacorresistencia Bacteriana , Impedancia Eléctrica , Diseño de Equipo , Humanos , Klebsiella pneumoniae/química , Klebsiella pneumoniae/efectos de los fármacos , Dispositivos Laboratorio en un Chip , Meropenem/administración & dosificación , Pruebas de Sensibilidad Microbiana/instrumentación , Técnicas Analíticas Microfluídicas/instrumentación , Técnicas Analíticas Microfluídicas/métodos
20.
Nat Commun ; 11(1): 5374, 2020 10 23.
Artículo en Inglés | MEDLINE | ID: mdl-33097713

RESUMEN

The emergence of resistance to azithromycin complicates treatment of Neisseria gonorrhoeae, the etiologic agent of gonorrhea. Substantial azithromycin resistance remains unexplained after accounting for known resistance mutations. Bacterial genome-wide association studies (GWAS) can identify novel resistance genes but must control for genetic confounders while maintaining power. Here, we show that compared to single-locus GWAS, conducting GWAS conditioned on known resistance mutations reduces the number of false positives and identifies a G70D mutation in the RplD 50S ribosomal protein L4 as significantly associated with increased azithromycin resistance (p-value = 1.08 × 10-11). We experimentally confirm our GWAS results and demonstrate that RplD G70D and other macrolide binding site mutations are prevalent (present in 5.42% of 4850 isolates) and widespread (identified in 21/65 countries across two decades). Overall, our findings demonstrate the utility of conditional associations for improving the performance of microbial GWAS and advance our understanding of the genetic basis of macrolide resistance.


Asunto(s)
Farmacorresistencia Bacteriana/genética , Genoma Bacteriano , Estudio de Asociación del Genoma Completo , Neisseria gonorrhoeae/efectos de los fármacos , Neisseria gonorrhoeae/genética , Antibacterianos/farmacología , Azitromicina/farmacología , Sitios de Unión/genética , Gonorrea/tratamiento farmacológico , Gonorrea/microbiología , Humanos , Macrólidos/farmacología , Pruebas de Sensibilidad Microbiana , Mutación/efectos de los fármacos , ARN Ribosómico 23S/genética
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