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1.
Molecules ; 26(15)2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34361723

RESUMO

Genito-urinary tract infections have a high incidence in the general population, being more prevalent among women than men. These diseases are usually treated with antibiotics, but very frequently, they are recurrent and lead to the creation of resistance and are associated with increased morbidity and mortality. For this reason, it is necessary to develop new compounds for their treatment. In this work, our objective is to review the characteristics of the compounds of a new formulation called Itxasol© that is prescribed as an adjuvant for the treatment of UTIs and composed of ß-arbutin, umbelliferon and n-acetyl cysteine. This formulation, based on biomimetic principles, makes Itxasol© a broad-spectrum antibiotic with bactericidal, bacteriostatic and antifungal properties that is capable of destroying the biofilm and stopping its formation. It also acts as an anti-inflammatory agent, without the adverse effects associated with the recurrent use of antibiotics that leads to renal nephrotoxicity and other side effects. All these characteristics make Itxasol© an ideal candidate for the treatment of UTIs since it behaves like an antibiotic and with better characteristics than other adjuvants, such as D-mannose and cranberry extracts.


Assuntos
Acetilcisteína/uso terapêutico , Arbutina/uso terapêutico , Produtos Biológicos/uso terapêutico , Umbeliferonas/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Acetilcisteína/química , Antibacterianos/química , Antibacterianos/uso terapêutico , Anti-Inflamatórios/química , Anti-Inflamatórios/uso terapêutico , Antifúngicos/química , Antifúngicos/uso terapêutico , Arbutina/química , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Produtos Biológicos/química , Materiais Biomiméticos/química , Materiais Biomiméticos/uso terapêutico , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Candida/patogenicidade , Combinação de Medicamentos , Feminino , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/crescimento & desenvolvimento , Bactérias Gram-Negativas/patogenicidade , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/crescimento & desenvolvimento , Bactérias Gram-Positivas/patogenicidade , Humanos , Masculino , Testes de Sensibilidade Microbiana , Umbeliferonas/química , Infecções Urinárias/microbiologia , Infecções Urinárias/patologia
2.
Viruses ; 13(7)2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34372554

RESUMO

Urinary tract infections (UTIs) are among the events that most frequently need medical intervention. Uropathogenic Escherichia coli are frequently their causative agents and the infections are sometimes complicated by the presence of polyresistant nosocomial strains. Phage therapy is a tool that has good prospects for the treatment of these infections. In the present study, we isolated and characterized two bacteriophages with broad host specificity against a panel of local uropathogenic E. coli strains and combined them into a phage cocktail. According to genome sequencing, these phages were closely related and belonged to the Tequatrovirus genus. The newly isolated phages showed very good activity on a panel of local clinical E. coli strains from urinary tract infections. In the form of a two-phage cocktail, they were active on E. coli strains belonging to phylogroups B2 and D, with relatively lower activity in B1 and no response in phylogroup A. Our study is a preliminary step toward the establishment of a national phage bank containing local, well-characterized phages with therapeutic potential for patients in Slovakia.


Assuntos
Myoviridae/genética , Terapia por Fagos/métodos , Escherichia coli Uropatogênica/genética , Antibacterianos/farmacologia , Bacteriófagos/genética , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/terapia , Especificidade de Hospedeiro/genética , Humanos , Eslováquia , Infecções Urinárias/microbiologia , Infecções Urinárias/terapia , Escherichia coli Uropatogênica/efeitos dos fármacos , Escherichia coli Uropatogênica/isolamento & purificação , Fatores de Virulência/genética
3.
BMC Infect Dis ; 21(1): 823, 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34399680

RESUMO

BACKGROUND: Urinary tract infections (UTI) are often over-diagnosed and over-treated, which can induce and select for resistant pathogens. After observing wide-spread outpatient use of ertapenem, a broad-spectrum antibiotic, a structured antimicrobial stewardship initiative (ASI) to improve appropriate antimicrobial prescribing was undertaken. ASI objectives were to achieve a goal of reducing ertapenem utilization for extended spectrum beta lactamase Enterobacteriaceae (ESBL-EB) UTI by 10% and evaluate the clinical outcomes associated with the ASI. METHODS: A pre-to-post cohort study was conducted at a single-center integrated healthcare system between November 1, 2014 and February 26, 2017. An intensive, 90-day, pharmacist-driven, structured ASI was implemented between November 1, 2015 and January 29, 2016. Female patients aged ≥18 years who were treated for an uncomplicated, ESBL-EB urinary tract infection (UTI) were included. Primary outcome was clinical resolution defined as cure, persistence, relapse and recurrence. Secondary outcome measured was monthly ertapenem use expressed as number of days of therapy (DOT)/1000 adjusted patient days (APD). Segmented regression analysis for interrupted time series was performed to estimate ASI intervention effect. RESULTS: A total of 184 patients were included in the study. Ertapenem utilization decreased from 0.0145 DOT/1000 APD in Nov. 2014 to 0.0078 DOT/1000 APD Feb. 2017(p < 0.01). The mean ertapenem DOT declined 19% overall from the pre vs. post intervention periods (32 vs 26, p < 0.01). Frequency of recurrent UTIs between treatments did not significantly differ and no adverse effects were reported in patients treated with aminoglycosides. CONCLUSIONS: A structured ASI for uncomplicated ESBL-EB UTI was associated with a clinically meaningful decrease in ertapenem utilization and once-daily, 5-day aminoglycoside treatment was well-tolerated.


Assuntos
Aminoglicosídeos/uso terapêutico , Antibacterianos/uso terapêutico , Gestão de Antimicrobianos , Infecções por Enterobacteriaceae/tratamento farmacológico , Enterobacteriaceae/efeitos dos fármacos , Ertapenem/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Adolescente , Adulto , Estudos de Coortes , Enterobacteriaceae/isolamento & purificação , Feminino , Humanos , Pacientes Ambulatoriais , Melhoria de Qualidade , Estudos Retrospectivos , Resultado do Tratamento , Infecções Urinárias/microbiologia , beta-Lactamases
4.
BMC Infect Dis ; 21(1): 637, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215203

RESUMO

BACKGROUND: Cedecea neteri is a gram-negative, oxidase-negative bacillus, a rare pathogen. Few reports are emerging globally about its antimicrobial resistance pattern especially in immunocompromised individuals with comorbidities. CASE PRESENTATION: In this paper, we report the first case of C. neteri causing urinary tract infection in a pregnant woman at a specialty care hospital in the Northern Emirates of Ras al Khaimah, UAE. DISCUSSION AND CONCLUSION: C. neteri is a rare and unusual pathogen, unlike routine gram-negative urinary tract pathogens from the family of Enterobacteriaceae and therefore may be missed or misidentified by routine laboratories using conventional microbiology identification techniques. Hence, Cedecea infections may be under-reported. Physicians and microbiology technicians must be aware of such a rare pathogen, as most of the isolates are multi-drug-resistant and require combined antibiotic treatment with beta-lactamase inhibitors and hence pose a treatment challenge especially in immunocompromised patients with comorbidities. In recent years, it has been reported as an emerging opportunistic pathogen.


Assuntos
Infecções por Enterobacteriaceae/epidemiologia , Enterobacteriaceae/isolamento & purificação , Poli-Hidrâmnios/fisiopatologia , Gestantes , Infecções Urinárias/epidemiologia , Adulto , Antibacterianos/uso terapêutico , Enterobacteriaceae/efeitos dos fármacos , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/microbiologia , Feminino , Humanos , Gravidez , Prognóstico , Emirados Árabes Unidos/epidemiologia , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia
5.
JAMA ; 326(4): 324-331, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34313686

RESUMO

Importance: Determination of optimal treatment durations for common infectious diseases is an important strategy to preserve antibiotic effectiveness. Objective: To determine whether 7 days of treatment is noninferior to 14 days when using ciprofloxacin or trimethoprim/sulfamethoxazole to treat urinary tract infection (UTI) in afebrile men. Design, Setting, and Participants: Randomized, double-blind, placebo-controlled noninferiority trial of afebrile men with presumed symptomatic UTI treated with ciprofloxacin or trimethoprim/sulfamethoxazole at 2 US Veterans Affairs medical centers (enrollment, April 2014 through December 2019; final follow-up, January 28, 2020). Of 1058 eligible men, 272 were randomized. Interventions: Participants continued the antibiotic prescribed by their treating clinician for 7 days of treatment and were randomized to receive continued antibiotic therapy (n = 136) or placebo (n = 136) for days 8 to 14 of treatment. Main Outcomes and Measures: The prespecified primary outcome was resolution of UTI symptoms by 14 days after completion of active antibiotic treatment. A noninferiority margin of 10% was selected. The as-treated population (participants who took ≥26 of 28 doses and missed no more than 2 consecutive doses) was used for the primary analysis, and a secondary analysis included all patients as randomized, regardless of treatment adherence. Secondary outcomes included recurrence of UTI symptoms and/or adverse events within 28 days of stopping study medication. Results: Among 272 patients (median [interquartile range] age, 69 [62-73] years) who were randomized, 100% completed the trial and 254 (93.4%) were included in the primary as-treated analysis. Symptom resolution occurred in 122/131 (93.1%) participants in the 7-day group vs 111/123 (90.2%) in the 14-day group (difference, 2.9% [1-sided 97.5% CI, -5.2% to ∞]), meeting the noninferiority criterion. In the secondary as-randomized analysis, symptom resolution occurred in 125/136 (91.9%) participants in the 7-day group vs 123/136 (90.4%) in the 14-day group (difference, 1.5% [1-sided 97.5% CI, -5.8% to ∞]) Recurrence of UTI symptoms occurred in 13/131 (9.9%) participants in the 7-day group vs 15/123 (12.9%) in the 14-day group (difference, -3.0% [95% CI, -10.8% to 6.2%]; P = .70). Adverse events occurred in 28/136 (20.6%) participants in the 7-day group vs 33/136 (24.3%) in the 14-day group. Conclusions and Relevance: Among afebrile men with suspected UTI, treatment with ciprofloxacin or trimethoprim/sulfamethoxazole for 7 days was noninferior to 14 days of treatment with regard to resolution of UTI symptoms by 14 days after antibiotic therapy. The findings support the use of a 7-day course of ciprofloxacin or trimethoprim/sulfamethoxazole as an alternative to a 14-day course for treatment of afebrile men with UTI. Trial Registration: ClinicalTrials.gov identifier: NCT01994538.


Assuntos
Antibacterianos/administração & dosagem , Ciprofloxacina/administração & dosagem , Combinação Trimetoprima e Sulfametoxazol/administração & dosagem , Infecções Urinárias/tratamento farmacológico , Idoso , Antibacterianos/efeitos adversos , Ciprofloxacina/efeitos adversos , Método Duplo-Cego , Esquema de Medicação , Duração da Terapia , Humanos , Masculino , Pessoa de Meia-Idade , Combinação Trimetoprima e Sulfametoxazol/efeitos adversos , Infecções Urinárias/microbiologia , Urina/microbiologia
6.
Biosensors (Basel) ; 11(6)2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205292

RESUMO

Consumption of cranberries is associated with the putative effects of preventing urinary tract infections (UTIs). Cranberry proanthocyanidins (PAC) contain unusual double A-type linkages, which are associated with strong interactions with surface virulence factors found on UTI-causing bacteria such as extra-intestinal pathogenic Escherichia coli (ExPEC), depicting in bacterial agglutination processes. In this work, we demonstrated the efficacy of cranberry PAC (200 µg/mL) to agglutinate ExPEC (5.0 × 108 CFU/mL) in vitro as a selective interaction for the design of functionalized biosensors for potential detection of UTIs. We fabricated functionalized screen-printed electrodes (SPEs) by modifying with PAC-polyaniline (PANI) nanocomposites and tested the effectiveness of the PAC-PANI/SPE biosensor for detecting the presence of ExPEC in aqueous suspensions. Results indicated that the PAC-PANI/SPE was highly sensitive (limit of quantification of 1 CFU/mL of ExPEC), and its response was linear over the concentration range of 1-70,000 CFU/mL, suggesting cranberry PAC-functionalized biosensors are an innovative alternative for the detection and diagnosis of ExPEC-associated UTIs. The biosensor was also highly selective, reproducible, and stable.


Assuntos
Bactérias , Nanocompostos/análise , Proantocianidinas/análise , Infecções Urinárias , Compostos de Anilina , Escherichia coli , Frutas , Humanos , Extratos Vegetais , Infecções Urinárias/microbiologia , Vaccinium macrocarpon
7.
Nucleic Acids Res ; 49(13): 7375-7388, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34181709

RESUMO

DNA methylation is a common epigenetic mark that influences transcriptional regulation, and therefore cellular phenotype, across all domains of life. In particular, both orphan methyltransferases and those from phasevariable restriction modification systems (RMSs) have been co-opted to regulate virulence epigenetically in many bacteria. We now show that three distinct non-phasevariable Type I RMSs in Escherichia coli have no measurable impact on gene expression, in vivo virulence, or any of 1190 in vitro growth phenotypes. We demonstrated this using both Type I RMS knockout mutants as well as heterologous installation of Type I RMSs into two E. coli strains. These data provide three clear and currently rare examples of restriction modification systems that have no impact on their host organism's gene regulation. This leads to the possibility that other such nonregulatory methylation systems may exist, broadening our view of the potential role that RMSs may play in bacterial evolution.


Assuntos
Metilação de DNA , Enzimas de Restrição-Modificação do DNA , Escherichia coli/genética , Animais , Escherichia coli/crescimento & desenvolvimento , Escherichia coli/metabolismo , Infecções por Escherichia coli/microbiologia , Regulação Bacteriana da Expressão Gênica , Camundongos , Infecções Urinárias/microbiologia , Escherichia coli Uropatogênica/genética , Escherichia coli Uropatogênica/crescimento & desenvolvimento , Escherichia coli Uropatogênica/metabolismo , Escherichia coli Uropatogênica/patogenicidade
8.
BMC Infect Dis ; 21(1): 572, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34126951

RESUMO

BACKGROUND: Urinary tract infections (UTIs) are the most common infections caused by Gram-negative bacteria and represent a major healthcare burden. Carbapenem-resistant (CR) strains of Enterobacterales and non-lactose fermenting pathogens further complicate treatment approaches. METHODS: We conducted a retrospective analysis of the US Premier Healthcare Database (2014-2019) in hospitalised adults with a UTI to estimate the healthcare burden of Gram-negative CR UTIs among patients with or without concurrent bacteraemia. RESULTS: Among the 47,496 patients with UTI analysed, CR infections were present in 2076 (4.4%). Bacteraemia was present in 24.5% of all UTI patients, and 1.7% of these were caused by a CR pathogen. The most frequent CR pathogens were Pseudomonas aeruginosa (49.4%) and Klebsiella pneumoniae (14.2%). Patients with CR infections had a significantly longer hospital length of stay (LOS) (median [range] 8 [5-12] days vs 6 [4-10] days, P < 0.001), were less likely to be discharged home (38.4% vs 51.0%, P < 0.001), had a higher readmission rate (22.6% vs 13.5%, P < 0.001), and had greater LOS-associated charges (mean US$ 91,752 vs US$ 66,011, P < 0.001) than patients with carbapenem-susceptible (CS) infections, respectively. The impact of CR pathogens was greater in patients with bacteraemia (or urosepsis) and these CR urosepsis patients had a significantly higher rate of mortality than those with CS urosepsis (10.5% vs 6.0%, P < 0.001). CONCLUSIONS: Among hospitalised patients with UTIs, the presence of a CR organism and bacteraemia increased the burden of disease, with worse outcomes and higher hospitalisation charges than disease associated with CS pathogens and those without bacteraemia.


Assuntos
Carbapenêmicos/farmacologia , Farmacorresistência Bacteriana , Bactérias Gram-Negativas/fisiologia , Infecções Urinárias/economia , Infecções Urinárias/microbiologia , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/economia , Bacteriemia/epidemiologia , Bacteriemia/microbiologia , Efeitos Psicossociais da Doença , Feminino , Bactérias Gram-Negativas/classificação , Hospitalização/economia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia , Infecções Urinárias/epidemiologia
9.
BMC Infect Dis ; 21(1): 571, 2021 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-34126937

RESUMO

BACKGROUND: Antibiotic resistance is increasing among urinary pathogens, resulting in worse clinical and economic outcomes. We analysed factors associated with antibiotic-resistant bacteria (ARB) in patients hospitalized for urinary tract infection, using the comprehensive French national claims database. METHODS: Hospitalized urinary tract infections were identified from 2015 to 2017. Cases (due to ARB) were matched to controls (without ARB) according to year, age, sex, infection, and bacterium. Healthcare-associated (HCAI) and community-acquired (CAI) infections were analysed separately; logistic regressions were stratified by sex. RESULTS: From 9460 cases identified, 6468 CAIs and 2855 HCAIs were matched with controls. Over a 12-months window, the risk increased when exposure occurred within the last 3 months. The following risk factors were identified: antibiotic exposure, with an OR reaching 3.6 [2.8-4.5] for men with CAI, mostly associated with broad-spectrum antibiotics; surgical procedure on urinary tract (OR 2.0 [1.5-2.6] for women with HCAI and 1.3 [1.1-1.6] for men with CAI); stay in intensive care unit > 7 days (OR 1.7 [1.2-2.6] for men with HCAI). Studied co-morbidities had no impact on ARB. CONCLUSIONS: This study points out the critical window of 3 months for antibiotic exposure, confirms the impact of broad-spectrum antibiotic consumption on ARB, and supports the importance of prevention during urological procedures, and long intensive care unit stays.


Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Seguro Saúde/estatística & dados numéricos , Infecções Urinárias/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , França/epidemiologia , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Infecções Urinárias/microbiologia
10.
BMC Vet Res ; 17(1): 199, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-34044828

RESUMO

BACKGROUND: The objective of the study was to report the incidence and risk factors associated with positive urine bacterial cultures as well as long-term outcome in cats with subcutaneous ureteral bypass (SUB) devices. RESULTS: Medical records of cats that underwent SUB device placement were retrospectively reviewed. Signalment of the cat, laterality of the ureteral obstruction, surgery, anesthesia and hospitalization duration, bacterial culture results and follow-up data were retrieved. Thirty-two cats met the inclusion criteria. Four cats (12.5%) had a positive intraoperative culture, with two of them being treated successfully. Ten cats out of 28 (35.7%) were documented with a positive urine culture during follow-up period, with a median time between discharge and identification of the first positive urine culture of 159 days (range 8-703 days). Bacteriuria resolved in 60% of cats (6/10). Escherichia coli was the most common organism, isolated in 4 out of 10 postoperative urine cultures. Overall, subclinical bacteriura was documented for 6 of 32 (18.8%) cats and 5 of 32 (15.6%) cats displayed clinicals signs suggestive of persistent UTI. One cat had subclinical bacteriuria. Three cats died during the follow-up period. There was a significant difference between negative and positive urine bacterial culture groups in median hospitalization duration (5 days versus 6 days, P = 0.022) and in median body condition score (5/9 versus 4/9, P = 0.03). Cats with a longer hospital stay and with a lower body condition score were more likely to have a positive urine culture during follow-up period. CONCLUSIONS: SUB device placement surgery is associated with complications such as chronic bacteriuria. Bacteriuria in our study resolved with appropriate antibiotic treatment in more than half of cats. Risk factors identified for positive urine culture were a longer hospitalization duration and a decreased body condition score.


Assuntos
Doenças do Gato/cirurgia , Ureter/cirurgia , Ureterolitíase/veterinária , Infecções Urinárias/veterinária , Animais , Bactérias/isolamento & purificação , Doenças do Gato/microbiologia , Doenças do Gato/urina , Gatos , Feminino , Incidência , Masculino , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Ureterolitíase/cirurgia , Infecções Urinárias/etiologia , Infecções Urinárias/microbiologia
11.
Am J Physiol Cell Physiol ; 321(1): C134-C146, 2021 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-33979212

RESUMO

The local environment forces a selection of bacteria that might invade the urinary tract, allowing only the most virulent to access the kidney. Quite similar to the diet in setting the stage for the gut microbiome, renal function determines the conditions for bacteria-host interaction in the urinary tract. In the kidney, the term local environment or microenvironment is completely justified because the environment literally changes within a few micrometers. The precise composition of the urine is a function of the epithelium lining the microdomain, and the microenvironment in the kidney shows more variation in the content of nutrients, ion composition, osmolality, and pH than any other site of bacteria-host interaction. This review will cover some of the aspects of bacterial-host interaction in this unique setting and how uropathogenic bacteria can alter the condition for bacteria-host interaction. There will be a particular focus on the recent findings regarding how bacteria specifically trigger host paracrine signaling, via release of extracellular ATP and activation of P2 purinergic receptors. These finding will be discussed from the perspective of severe urinary tract infections, including pyelonephritis and urosepsis.


Assuntos
Infecções por Escherichia coli/genética , Proteínas de Escherichia coli/genética , Proteínas Hemolisinas/genética , Pielonefrite/genética , Receptores Purinérgicos P2/genética , Sepse/genética , Infecções Urinárias/genética , Escherichia coli Uropatogênica/genética , Trifosfato de Adenosina/metabolismo , Anoctamina-1/genética , Anoctamina-1/metabolismo , Infecções por Escherichia coli/metabolismo , Infecções por Escherichia coli/microbiologia , Infecções por Escherichia coli/patologia , Proteínas de Escherichia coli/metabolismo , Regulação da Expressão Gênica , Proteínas Hemolisinas/metabolismo , Interações Hospedeiro-Patógeno/genética , Humanos , Concentração de Íons de Hidrogênio , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Comunicação Parácrina , Pielonefrite/metabolismo , Pielonefrite/microbiologia , Pielonefrite/patologia , Receptores Purinérgicos P2/metabolismo , Sepse/metabolismo , Sepse/microbiologia , Sepse/patologia , Transdução de Sinais , Infecções Urinárias/metabolismo , Infecções Urinárias/microbiologia , Infecções Urinárias/patologia , Escherichia coli Uropatogênica/crescimento & desenvolvimento , Escherichia coli Uropatogênica/metabolismo , Escherichia coli Uropatogênica/patogenicidade
12.
Medicine (Baltimore) ; 100(21): e26091, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032746

RESUMO

INTRODUCTION: This work reports a patient with recurrent renal calculi subjected to three surgeries in half a year to be in the same position, and the high-throughput sequencing data showed different species in the renal pus and urine samples, which suggested that partial renal infection or stone formation can be judged by the bacteria in urine. PATIENT CONCERNS: The female patient aged 43 years was referred to the authors' department on April 13, 2020, due to left waist pain and fever for 3 days. DIAGNOSIS: Kidney stones and hydronephrosis were determined by a urinary system computed tomography scan. INTERVENTIONS: On April 20, 2020 and June 15, 2020, the patient was successfully treated with left percutaneous nephrolithotomy twice under general anesthesia. An investigation on the health and eating habits of the patient within 6 months was completed at the last admission. The components of the second renal calculus sample were analyzed with an infrared spectrum analyzer. The third renal stone (renal pus, triplicates) was subjected to microbial metagenome sequencing, and urine samples before and after surgery were subjected to 16S RNA sequencing by SEQHEALTH (Wuhan, China). OUTCOMES: After percutaneous nephrolithotomy, the left kidney stones were basically cleared, stone analysis revealed that the main components were calcium oxalate monohydrate, silica, and a small amount of calcium oxalate dehydrate. Although the urine samples exhibited differences, the renal pus and urine sample shared a single species. CONCLUSION: It is not clear that the prospects of partial renal infection or stone formation can be judged by the bacteria in urine.


Assuntos
Infecções por Helicobacter/diagnóstico , Hidronefrose/diagnóstico , Cálculos Renais/diagnóstico , Nefrolitotomia Percutânea/efeitos adversos , Infecções Urinárias/diagnóstico , Adulto , DNA Bacteriano/isolamento & purificação , Feminino , Infecções por Helicobacter/complicações , Infecções por Helicobacter/microbiologia , Infecções por Helicobacter/cirurgia , Helicobacter pylori , Humanos , Hidronefrose/microbiologia , Hidronefrose/cirurgia , Cálculos Renais/microbiologia , Cálculos Renais/cirurgia , Metagenoma/genética , RNA Ribossômico 16S/genética , Recidiva , Reoperação , Infecções Urinárias/complicações , Infecções Urinárias/microbiologia , Infecções Urinárias/cirurgia
13.
Nat Commun ; 12(1): 2587, 2021 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-33972537

RESUMO

Host cells use several anti-bacterial pathways to defend against pathogens. Here, using a uropathogenic Escherichia coli (UPEC) infection model, we demonstrate that bacterial infection upregulates RhoB, which subsequently promotes intracellular bacteria clearance by inducing LC3 lipidation and autophagosome formation. RhoB binds with Beclin 1 through its residues at 118 to 140 and the Beclin 1 CCD domain, with RhoB Arg133 being the key binding residue. Binding of RhoB to Beclin 1 enhances the Hsp90-Beclin 1 interaction, preventing Beclin 1 degradation. RhoB also directly interacts with Hsp90, maintaining RhoB levels. UPEC infections increase RhoB, Beclin 1 and LC3 levels in bladder epithelium in vivo, whereas Beclin 1 and LC3 levels as well as UPEC clearance are substantially reduced in RhoB+/- and RhoB-/- mice upon infection. We conclude that when stimulated by UPEC infections, host cells promote UPEC clearance through the RhoB-Beclin 1-HSP90 complex, indicating RhoB may be a useful target when developing UPEC treatment strategies.


Assuntos
Autofagossomos/metabolismo , Proteína Beclina-1/metabolismo , Infecções por Escherichia coli/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Infecções Urinárias/metabolismo , Escherichia coli Uropatogênica/crescimento & desenvolvimento , Proteína rhoB de Ligação ao GTP/metabolismo , Animais , Autofagossomos/genética , Autofagossomos/ultraestrutura , Proteína Beclina-1/genética , Linhagem Celular , Epitélio/metabolismo , Epitélio/microbiologia , Infecções por Escherichia coli/genética , Infecções por Escherichia coli/microbiologia , Feminino , Técnicas de Silenciamento de Genes , Proteínas de Choque Térmico HSP90/genética , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microscopia Eletrônica de Transmissão , Proteínas Associadas aos Microtúbulos/metabolismo , Ligação Proteica , Estabilidade Proteica , RNA Interferente Pequeno , Proteínas Recombinantes , Bexiga Urinária/metabolismo , Bexiga Urinária/microbiologia , Infecções Urinárias/genética , Infecções Urinárias/microbiologia , Escherichia coli Uropatogênica/patogenicidade , Proteína rhoB de Ligação ao GTP/genética
14.
Vet Rec ; 188(9): e60, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33960452

RESUMO

BACKGROUND: The increasing emergence of multidrug-resistant bacteria, causing urinary tract infections (UTI) in dogs and cats, represents a great therapeutic challenge and a public health concern. METHODS: Laboratory records of 4943 urinary microbiological diagnosis results and antimicrobial resistance profiles of suspected UTI cases in dogs and cats were analysed from 2016 to 2018 in Spain. RESULTS: This study showed a higher percentage of positive microbiological diagnoses in dogs (42%, 1368/3270) than in cats (27%, 457/1673). Although Escherichia coli was the most frequently isolated bacterium, the frequency of antimicrobial susceptibility of E. coli isolates was lower compared to other bacterial species like Enterococcus spp., Staphylococcus spp., Klebsiella pneumoniae, Pseudomonas aeruginosa, Enterobacter (E. cloacae), and Proteus mirabilis. The antimicrobial susceptibility testing of Gram-positive cocci showed higher levels of resistance in cats to common beta-lactams used for the treatment of complicated UTIs, as well as to fluoroquinolones, aminoglycosides, and carbapenems. Moreover, enterobacteria (E. coli, K. pneumoniae, and P. mirabilis) from cats presented high resistance frequencies to beta-lactams, including third- and fourth-generation cephalosporins and fluoroquinolones. CONCLUSION: This study updates data on the current antimicrobial resistance in UTI bacteria from companion animals in Spain, which may help to guide clinicians for the appropriate use of antimicrobials.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Infecções Bacterianas/veterinária , Doenças do Gato/microbiologia , Doenças do Cão/microbiologia , Farmacorresistência Bacteriana Múltipla , Infecções Urinárias/veterinária , Animais , Bactérias/isolamento & purificação , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Doenças do Gato/tratamento farmacológico , Gatos , Doenças do Cão/tratamento farmacológico , Cães , Feminino , Masculino , Animais de Estimação , Espanha , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia
15.
PLoS Pathog ; 17(4): e1009534, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33901267

RESUMO

Long-term survival of bacterial pathogens during persistent bacterial infections can be associated with antibiotic treatment failure and poses a serious public health problem. Infections caused by the Gram-negative pathogen Pseudomonas aeruginosa, which can cause both acute and chronic infections, are particularly challenging due to its high intrinsic resistance to antibiotics. The ineffectiveness of antibiotics is exacerbated when bacteria reside intracellularly within host cells where they can adopt a drug tolerant state. While the early steps of adherence and entry of P. aeruginosa into mammalian cells have been described, the subsequent fate of internalized bacteria, as well as host and bacterial molecular pathways facilitating bacterial long-term survival, are not well defined. In particular, long-term survival within bladder epithelial cells has not been demonstrated and this may have important implications for the understanding and treatment of UTIs caused by P. aeruginosa. Here, we demonstrate and characterize the intracellular survival of wild type (WT) P. aeruginosa inside bladder epithelial cells and a mutant with a disruption in the bacterial two-component regulator AlgR that is unable to survive intracellularly. Using simultaneous dual RNA-seq transcriptional profiling, we define the transcriptional response of intracellular bacteria and their corresponding invaded host cells. The bacterial transcriptional response demonstrates that WT bacteria rapidly adapt to the stress encountered in the intracellular environment in contrast to ΔalgR bacteria. Analysis of the host transcriptional response to invasion suggests that the NF-κB signaling pathway, previously shown to be required for extracellular bacterial clearance, is paradoxically also required for intracellular bacterial survival. Lastly, we demonstrate that intracellular survival is important for pathogenesis of P. aeruginosa in vivo using a model of murine urinary tract infection. We propose that the unappreciated ability of P. aeruginosa to survive intracellularly may play an important role in contributing to the chronicity and recurrence of P. aeruginosa in urinary tract infections.


Assuntos
Adaptação Fisiológica/genética , Interações Hospedeiro-Patógeno/genética , Pseudomonas aeruginosa/fisiologia , Animais , Células Cultivadas , Feminino , Perfilação da Expressão Gênica , Regulação Bacteriana da Expressão Gênica , Aptidão Genética/fisiologia , Espaço Intracelular/genética , Espaço Intracelular/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Viabilidade Microbiana/genética , Infecções por Pseudomonas/genética , Infecções por Pseudomonas/microbiologia , Infecções Urinárias/genética , Infecções Urinárias/microbiologia
16.
Zoonoses Public Health ; 68(5): 452-463, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33844465

RESUMO

The present study aimed to estimate the proportion of bacterial urinary tract infection (UTI) in dogs and cats, assess risks associated with bacterial UTI, and to determine bacterial isolates' antimicrobial susceptibility and resistance pattern from the urinary tract of dogs and cats with urologic problems. The medical records from animals visiting Chiang Mai University Small Animal Veterinary Teaching Hospital between January 2012 and December 2016 were reviewed. In total, 203 dogs and 49 cats with urinary tract diseases that had samples submitted for bacterial culture were identified;198 and 24 bacterial isolates were recovered from dogs' and cats' submitted samples, respectively. At least one episode of bacterial UTI was detected in 75.4% (95% CI: 69.4-81.3) of dogs and in 40.8% (95% CI: 26.6-55.1) of cats with UTI and submitted urine cultures. Of 242 submitted urinary samples from dogs and 60 urinary samples from cats, bacteria were identified in 74.0% (95% CI: 68.4-79.5) and 38.3% (95% CI: 26.0-50.6), respectively. The most common pathogen of bacteria positive cultured from dogs was Staphylococcus spp. (30.3%), followed by Escherichia coli (16.7%), and Proteus spp. (13.6%). For cats, the most common pathogen was Pseudomonas spp. (25.0%), followed by E. coli (20.8%) and Proteus spp. (16.7%). Staphylococcus spp. isolates from dogs and Proteus spp. isolates from cats were highly susceptible to Amoxicillin/clavulanic acid (AMC) at 88% and 75%, respectively. Of all isolated bacteria, 67.1% of the bacteria from dogs and 83.3% from cats were multidrug-resistant (MDR). The proportion of MDR-bacterial urinary tract infections in dogs and cats with urologic problems in this study was high. This observation raises concerns regarding the potential of zoonotic transmission of MDR-bacteria from these companion animals. The results suggested that AMC remains a good empirical drug for treating UTIs in dogs in this region.


Assuntos
Antibacterianos/farmacologia , Infecções Bacterianas/veterinária , Doenças do Gato/microbiologia , Doenças do Cão/microbiologia , Infecções Urinárias/veterinária , Animais , Bactérias/efeitos dos fármacos , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Doenças do Gato/epidemiologia , Gatos , Doenças do Cão/epidemiologia , Cães , Feminino , Masculino , Estudos Retrospectivos , Tailândia/epidemiologia , Infecções Urinárias/epidemiologia , Infecções Urinárias/microbiologia
17.
J Urol ; 206(3): 662-668, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33904798

RESUMO

PURPOSE: Prophylactic antibiotics are routinely given at the time of catheter removal post-radical prostatectomy (RP). The low rate of infectious complications entails that large sample sizes are required for randomized controlled trials, a challenge given the cost of standard randomized controlled trials. We evaluated infectious complications associated with 1 vs 3 days of prophylactic antibiotics at the time of catheter removal post-RP using a novel, clinically integrated trial with randomization at the surgeon level. MATERIALS AND METHODS: Surgeons were cluster randomized for periods of 3 months to prescribe 1-day vs 3-day regimen of prophylactic antibiotics at the time of catheter removal. The primary end point was an infectious complication as routinely captured by nursing phone call within 10 days of catheter removal and defined as positive urine cultures (≥105 CFU) and at least 1 of the following symptoms: fever (>38°C), urgency, frequency, dysuria or suprapubic tenderness. RESULTS: A total of 824 patients were consented and underwent RP with, respectively, 389 and 435 allocated to 1-day and 3-day antibiotics, predominantly ciprofloxacin. Accrual was achieved within 3 years: 95% vs 88% of patients received the allocated 3-day vs 1-day antibiotic regimen. There were 0 urinary tract infections (0%) in the 1-day regimen and 3 urinary tract infections (0.7%) in the 3-day regimen, meeting our prespecified criterion for declaring the 1-day regimen to be noninferior. CONCLUSIONS: A clinically integrated trial using cluster randomization accrued rapidly with no important logistical problems and negligible burden on surgeons. If surgeons choose to prescribe empiric prophylactic antibiotics after catheter removal following RP, then the duration should not exceed 1 day.


Assuntos
Antibioticoprofilaxia/métodos , Infecções Relacionadas a Cateter/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Prostatectomia/efeitos adversos , Infecções Urinárias/epidemiologia , Idoso , Antibacterianos/administração & dosagem , Antibioticoprofilaxia/estatística & dados numéricos , Infecções Relacionadas a Cateter/microbiologia , Infecções Relacionadas a Cateter/prevenção & controle , Cateteres/efeitos adversos , Ciprofloxacina/administração & dosagem , Estudos Cross-Over , Remoção de Dispositivo/efeitos adversos , Esquema de Medicação , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/microbiologia , Complicações Pós-Operatórias/prevenção & controle , Próstata/cirurgia , Neoplasias da Próstata/cirurgia , Fatores de Tempo , Resultado do Tratamento , Cateterismo Urinário/efeitos adversos , Cateterismo Urinário/instrumentação , Infecções Urinárias/microbiologia , Infecções Urinárias/prevenção & controle
18.
BMC Urol ; 21(1): 61, 2021 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-33849512

RESUMO

BACKGROUND: While the resistance rates of commonly detected uropathogens are well described, those of less frequent Gram-negative uropathogenic bacteria have seldom been reported. The aim of this study was to examine the resistance rates of less frequent uropathogenic Gram-negatives in a population of patients treated in a Department of Urology of a tertiary referral centre in Central Europe over a period of 9 years. METHODS: Data on all positive urine samples from urological in- and out-patients were extracted form the Department of Clinical Microbiology database from 2011 to 2019. Numbers of susceptible and resistant isolates per year were calculated for these uropathogens: Acinetobacter spp. (n = 74), Citrobacter spp. (n = 60), Enterobacter spp. (n = 250), Morganella morganii (n = 194), Providencia spp. (n = 53), Serratia spp. (n = 82) and Stenotrophomonas maltophilia (n = 27). Antimicrobial agents selected for the survey included: ampicillin, amoxicillin/clavulanic acid, piperacillin/tazobactam; cefuroxime, cefotaxime, ceftazidime and cefepime; ciprofloxacin and ofloxacin; gentamicin and amikacin; ertapenem, meropenem and imipenem; trimethoprim-sulfamethoxazole (co-trimoxazole), nitrofurantoin and colistin. RESULTS: Penicillin derivatives have generally poor effect except piperacillin/tazobactam. Cefuroxime is not efficient unlike cefotaxime (except against Acinetobacter spp. and S. maltophilia). Susceptibility to fluoroquinolones is limited. Amikacin is somewhat more efficient than gentamicine but susceptibilities for both safely exceed 80%. Nitrofurantoin shows virtually no efficiency. Cotrimoxazole acts well against Citrobacter spp., Serratia spp. and it is the treatment of choice for S. maltophilia UTIs. Among carbapenems, ertapenem was less efficient than meropenem and imipenem except for S. maltophilia whose isolates were mostly not suceptible to any carbapenems. CONCLUSIONS: Uropathogenic microorganisms covered in this report are noteworthy for their frequently multi-drug resistant phenotypes. Knowledge of resistance patterns helps clinicians choose the right empirical antibiotic treatment when the taxonomical assignment of the isolate is known but sensitivity results are pending.


Assuntos
Farmacorresistência Bacteriana , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções Urinárias/microbiologia , Idoso , República Tcheca , Feminino , Bactérias Gram-Negativas/isolamento & purificação , Departamentos Hospitalares , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Centros de Atenção Terciária , Fatores de Tempo , Urologia
19.
BMC Infect Dis ; 21(1): 361, 2021 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-33865334

RESUMO

BACKGROUND: Urinary Tract Infection (UTI) is one of the most common bacterial infectious diseases which causes considerable morbidity and costly health problems. Uropathogenic Escherichia coli (UPEC), the most common pathogen causing UTI, is a highly heterogeneous group of extraintestinal pathogenic E. coli (ExPEC) which may carry a variety of virulence factors and belonging to different phylogenetic backgrounds. The current study aimed to investigate the frequency and association between various virulence factors (VFs) and phylogenetic groups of UPEC and commensal isolates. METHODS: UPEC and commensal E. coli strains isolated from UTI and feces of healthy humans were compared for the presence of VFs and phylogenetic groups. Association between virulence genes was investigated and cluster analysis was employed. RESULTS: According to the results, among a 30 virulence markers tested, the pathogenicity-associated island (PAI), papAH, papEF, fimH, fyuA, and traT genes prevalence were statistically significant in UPEC isolates. A strong association was found between the B2 and D phylogenetic groups and clinical isolates of UPEC; while, commensal isolates were mostly associated with phylogenetic group A. The aggregated VFs scores were more than twice higher in the UPEC isolates in comparison with the commensal isolates. Interestingly, the B2 group in both UPEC and commensal isolates had the highest VF scores. A strong positive association was found between several virulence genes. The clustering results demonstrated that UPEC or commensal E. coli isolates were highly heterogeneous due to different composition of their virulence gene pool and pathogenicity islands. CONCLUSION: Genetic structure and VFs of UPEC strains vary from region to region; therefore, to control the UTI, the epidemiological aspects and characterization of the UPEC isolates need to be investigated in different regions. Since UPEC isolates are generally originate from the commensal strains, it may be feasible to reduce the UTI burden by interfering the intestinal colonization, particularly in the highly pathogenic clonal lineages such as B2.


Assuntos
Infecções por Escherichia coli/microbiologia , Infecções Urinárias/microbiologia , Escherichia coli Uropatogênica , Fatores de Virulência/genética , Virulência/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Criança , Pré-Escolar , Infecções por Escherichia coli/epidemiologia , Proteínas de Escherichia coli/genética , Escherichia coli Extraintestinal Patogênica/genética , Escherichia coli Extraintestinal Patogênica/isolamento & purificação , Escherichia coli Extraintestinal Patogênica/patogenicidade , Feminino , Ilhas Genômicas/genética , Humanos , Lactente , Recém-Nascido , Irã (Geográfico)/epidemiologia , Masculino , Pessoa de Meia-Idade , Filogenia , Prevalência , Infecções Urinárias/epidemiologia , Escherichia coli Uropatogênica/classificação , Escherichia coli Uropatogênica/genética , Escherichia coli Uropatogênica/isolamento & purificação , Escherichia coli Uropatogênica/patogenicidade , Adulto Jovem
20.
BMC Infect Dis ; 21(1): 388, 2021 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-33902477

RESUMO

BACKGROUND: One of the leading long-term complications of type 2 diabetes mellitus (T2DM) includes renal dysfunction and urinary tract infections (UTI) which are considered to be prevalent in uncontrolled diabetes. Moreover, physiological factors like age, gender, duration of diabetes, other diabetic complications like neuropathy, autonomic neuropathy and glycosuria are also considered as predisposing factors for increased prevalence of UTI in diabetes which can be symptomatic or asymptomatic. METHODS: This was a cross-sectional, multi-centre study including diabetic patients from 12 clinical sites spread across major cities of Pakistan. The inclusion criteria were adult Pakistani population of age between 18 to 75 years both genders and suffering from T2DM irrespective of duration. A detailed clinical history of the past 3 months was recorded and, biochemical investigations of blood samples were conducted. Urine culture analysis performed identified the type of pathogen present and was done only for asymptomatic patients. RESULTS: A total of 745 type 2 diabetic patients were initially screened, out of 545 patients considered for final analysis 501 (91.92%) were negative and the rest 44 (8.08%) had positive urine culture. Female gender had a significantly higher proportion of positive urine culture (77.27%, p-value< 0.001). Body mass index and mean age had insignificant distribution among the two groups of positive and negative urine culture, with age 40-59 years having higher proportion (70.45%) in the positive group. Escherichia coli was detected in most of the positive samples (52.3%). All bacterial samples were found resistant to Ciprofloxacin. CONCLUSION: Diabetic Pakistani muslim female patients are identified to be at high risk of suffering from asymptomatic UTI and age more than 40 years is an important risk factor. Escherichia coli was the most common causative organism among people living in this geographical area.


Assuntos
Infecções Assintomáticas/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/etiologia , Escherichia coli/isolamento & purificação , Islamismo , Infecções Urinárias/epidemiologia , Infecções Urinárias/etiologia , Adolescente , Adulto , Fatores Etários , Idoso , Estudos Transversais , Infecções por Escherichia coli/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Paquistão/epidemiologia , Prevalência , Fatores de Risco , Fatores Sexuais , Urinálise , Infecções Urinárias/microbiologia , Infecções Urinárias/urina , Adulto Jovem
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