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1.
Rev Med Suisse ; 16(710): 1906-1911, 2020 Oct 14.
Artigo em Francês | MEDLINE | ID: mdl-33058575

RESUMO

Cephalosporins belong to the betalactam group and are frequently prescribed in both out and inpatient settings. Their broad spectrum of activity allows a varied use in most medical specialties, ranging from preoperative prophylaxis to treatment of febrile agranulocytosis. There are currently five generations of cephalosporins, mainly differentiated according to their structure, spectrum of activity and side-effect profile. So-called siderophore cephalosporins are active against many multiresistant bacteria, especially in cases of complicated urinary tract infections or ventilator-associated pneumonia. This article intends to review some general clinical principles in prescription and monitoring of patients treated with cephalosporins.


Assuntos
Cefalosporinas/uso terapêutico , Bactérias/efeitos dos fármacos , Cefalosporinas/farmacologia , Humanos , Prescrições , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia
2.
BMC Infect Dis ; 20(1): 673, 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32938424

RESUMO

BACKGROUND: Urinary tract infection is one of the most common bacterial infections in children. Understanding the characteristics of uropathogens and their antimicrobial susceptibility pattern in a particular setting can provide evidence for the appropriate management of cases. This study aimed to assess the bacterial profile of urinary tract infection, their antimicrobial susceptibility pattern and associated factors among clinically suspected children attending at Felege-Hiwot Comprehensive Specialized Hospital, Northwest Ethiopia. METHODS: A hospital-based cross-sectional study was conducted from February-April, 2019. A systematic sampling technique was employed. A mid-stream urine sample was inoculated on cystine lactose electrolyte deficient media and incubated for 24-48 h. Sub-culturing was done on Mac-Conkey and blood agar. Antimicrobial susceptibility test was done on Muller-Hinton agar. A binary logistic regression model was used to see the association between dependent and independent factors. A p-value< 0.05 at 95% CI was considered as statistically significant. RESULTS: The overall prevalence of urinary tract infection was 16.7% (95% CI 12.4-21.1). Both Gram-negative and Gram-positive bacterial isolates were recovered with a rate of 44/50 (88%) and 6/50 (12%) respectively. Among Gram-negative isolates, E. coli 28/44(63.6%) was predominant while S. saprophyticus 2/6(33.3%) was prevalent among Gram-positive bacterial isolates. Overall, a high level of resistance to ampicillin, augmentin, and tetracycline was shown by Gram-negative bacteria with a rate of 44/44(100%), 39/44(88.6%), and36/44 (81.8%) respectively. About 33/50(66%) of overall multidrug resistance was observed (95% CI 52-78). About six Gram-negative bacterial isolates were extended spectrum beta-lactamase (ESBL) producers. Having a history of urinary tract infection (P-0.003, AOR 1.86-22.15) and male uncircumcision (p-0.00, AOR 5.5-65.35) were the independent variables that associate for urinary tract infections. CONCLUSION: In the present study, the prevalence of urinary tract infection among children was high and considerably a high proportion of multidrug resistance was observed. This result will have a significant impact on the selection of appropriate antimicrobial agents for the treatment of urinary tract infection.


Assuntos
Infecções Urinárias/diagnóstico , Adolescente , Antibacterianos/farmacologia , Criança , Pré-Escolar , Estudos Transversais , Farmacorresistência Bacteriana Múltipla , Escherichia coli/efeitos dos fármacos , Escherichia coli/isolamento & purificação , Etiópia/epidemiologia , Feminino , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/isolamento & purificação , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/isolamento & purificação , Hospitais , Humanos , Lactente , Masculino , Testes de Sensibilidade Microbiana , Razão de Chances , Estudos Prospectivos , Infecções Urinárias/microbiologia , beta-Lactamases/genética , beta-Lactamases/metabolismo
4.
PLoS Biol ; 18(9): e3000856, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32941420

RESUMO

Antibiotic combination therapies are important for the efficient treatment of many types of infections, including those caused by antibiotic-resistant pathogens. Combination treatment strategies are typically used under the assumption that synergies are conserved across species and strains, even though recent results show that the combined treatment effect is determined by specific drug-strain interactions that can vary extensively and unpredictably, both between and within bacterial species. To address this problem, we present a new method in which antibiotic synergy is rapidly quantified on a case-by-case basis, allowing for improved combination therapy. The novel CombiANT methodology consists of a 3D-printed agar plate insert that produces defined diffusion landscapes of 3 antibiotics, permitting synergy quantification between all 3 antibiotic pairs with a single test. Automated image analysis yields fractional inhibitory concentration indices (FICis) with high accuracy and precision. A technical validation with 3 major pathogens, Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus, showed equivalent performance to checkerboard methodology, with the advantage of strongly reduced assay complexity and costs for CombiANT. A synergy screening of 10 antibiotic combinations for 12 E. coli urinary tract infection (UTI) clinical isolates illustrates the need for refined combination treatment strategies. For example, combinations of trimethoprim (TMP) + nitrofurantoin (NIT) and TMP + mecillinam (MEC) showed synergy, but only for certain individual isolates, whereas MEC + NIT combinations showed antagonistic interactions across all tested strains. These data suggest that the CombiANT methodology could allow personalized clinical synergy testing and large-scale screening. We anticipate that CombiANT will greatly facilitate clinical and basic research of antibiotic synergy.


Assuntos
Antibacterianos/administração & dosagem , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Sinergismo Farmacológico , Testes de Sensibilidade Microbiana/métodos , Algoritmos , Andinocilina/administração & dosagem , Andinocilina/farmacologia , Antibacterianos/farmacologia , Quimioterapia Combinada/métodos , Quimioterapia Combinada/normas , Escherichia coli/isolamento & purificação , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Humanos , Testes de Sensibilidade Microbiana/instrumentação , Nitrofurantoína/administração & dosagem , Nitrofurantoína/farmacologia , Infecções por Pseudomonas/tratamento farmacológico , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/isolamento & purificação , Reprodutibilidade dos Testes , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Staphylococcus aureus/isolamento & purificação , Trimetoprima/administração & dosagem , Trimetoprima/farmacologia , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia
5.
PLoS Pathog ; 16(8): e1008856, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32845936

RESUMO

Copper and superoxide are used by the phagocytes to kill bacteria. Copper is a host effector encountered by uropathogenic Escherichia coli (UPEC) during urinary tract infection in a non-human primate model, and in humans. UPEC is exposed to higher levels of copper in the gut prior to entering the urinary tract. Effects of pre-exposure to copper on bacterial killing by superoxide has not been reported. We hypothesized that copper-replete E. coli is more sensitive to killing by superoxide in vitro, and in activated macrophages. We utilized wild-type UPEC strain CFT073, and its isogenic mutants lacking copper efflux systems, superoxide dismutases (SODs), regulators of a superoxide dismutase, and complemented mutants to address this question. Surprisingly, our results reveal that copper protects UPEC against killing by superoxide in vitro. This copper-dependent protection was amplified in the mutants lacking copper efflux systems. Increased levels of copper and manganese were detected in UPEC exposed to sublethal concentration of copper. Copper activated the transcription of sodA in a SoxR- and SoxS-dependent manner resulting in enhanced levels of SodA activity. Importantly, pre-exposure to copper increased the survival of UPEC within RAW264.7 and bone marrow-derived murine macrophages. Loss of SodA, but not SodB or SodC, in UPEC obliterated copper-dependent protection from superoxide in vitro, and from killing within macrophages. Collectively, our results suggest a model in which sublethal levels of copper trigger the activation of SodA and SodC through independent mechanisms that converge to promote the survival of UPEC from killing by superoxide. A major implication of our findings is that bacteria colonizing copper-rich milieus are primed for efficient detoxification of superoxide.


Assuntos
Cobre/farmacologia , Infecções por Escherichia coli/tratamento farmacológico , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Superóxidos/toxicidade , Infecções Urinárias/tratamento farmacológico , Escherichia coli Uropatogênica/efeitos dos fármacos , Animais , Infecções por Escherichia coli/induzido quimicamente , Infecções por Escherichia coli/microbiologia , Feminino , Regulação Bacteriana da Expressão Gênica , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos CBA , Superóxido Dismutase/genética , Infecções Urinárias/induzido quimicamente , Infecções Urinárias/microbiologia
6.
Emerg Microbes Infect ; 9(1): 1958-1964, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32815458

RESUMO

Objectives Severe or critical COVID-19 is associated with intensive care unit admission, increased secondary infection rate, and would lead to significant worsened prognosis. Risks and characteristics relating to secondary infections in severe COVID-19 have not been described. Methods Severe and critical COVID-19 patients from Shanghai were included. We collected lower respiratory, urine, catheters, and blood samples according to clinical necessity and culture and mNGS were performed. Clinical and laboratory data were archived. Results We found 57.89% (22/38) patients developed secondary infections. The patient receiving invasive mechanical ventilation or in critical state has a higher chance of secondary infections (P<0.0001). The most common infections were respiratory, blood-stream and urinary infections, and in respiratory infections, the most detected pathogens were gram-negative bacteria (26, 50.00%), following by gram-positive bacteria (14, 26.92%), virus (6, 11.54%), fungi (4, 7.69%), and others (2, 3.85%). Respiratory Infection rate post high flow, tracheal intubation, and tracheotomy were 12.90% (4/31), 30.43% (7/23), and 92.31% (12/13) respectively. Secondary infections would lead to lower discharge rate and higher mortality rate. Conclusion Our study originally illustrated secondary infection proportion in severe and critical COVID-19 patients. Culture accompanied with metagenomics sequencing increased pathogen diagnostic rate. Secondary infections risks increased after receiving invasive respiratory ventilations and intravascular devices, and would lead to a lower discharge rate and a higher mortality rate.


Assuntos
Bacteriemia/patologia , Infecções Bacterianas/patologia , Infecções por Coronavirus/patologia , Fungemia/patologia , Micoses/patologia , Infecções Oportunistas/patologia , Pneumonia Viral/patologia , Infecções Respiratórias/patologia , Infecções Urinárias/patologia , Idoso , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Bacteriemia/virologia , Infecções Bacterianas/microbiologia , Infecções Bacterianas/mortalidade , Infecções Bacterianas/virologia , Betacoronavirus/patogenicidade , Infecções por Coronavirus/microbiologia , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/virologia , Estado Terminal , Feminino , Fungemia/microbiologia , Fungemia/mortalidade , Fungemia/virologia , Fungos/patogenicidade , Bactérias Gram-Negativas/patogenicidade , Bactérias Gram-Positivas/patogenicidade , Humanos , Unidades de Terapia Intensiva , Pulmão/microbiologia , Pulmão/patologia , Pulmão/virologia , Masculino , Pessoa de Meia-Idade , Micoses/microbiologia , Micoses/mortalidade , Micoses/virologia , Infecções Oportunistas/microbiologia , Infecções Oportunistas/mortalidade , Infecções Oportunistas/virologia , Pandemias , Pneumonia Viral/microbiologia , Pneumonia Viral/mortalidade , Pneumonia Viral/virologia , Respiração Artificial/efeitos adversos , Infecções Respiratórias/microbiologia , Infecções Respiratórias/mortalidade , Infecções Respiratórias/virologia , Estudos Retrospectivos , Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Infecções Urinárias/microbiologia , Infecções Urinárias/mortalidade , Infecções Urinárias/virologia
7.
PLoS Pathog ; 16(8): e1008707, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32780778

RESUMO

Proteus mirabilis, a Gram-negative uropathogen, is a major causative agent in catheter-associated urinary tract infections (CAUTI). Mannose-resistant Proteus-like fimbriae (MR/P) are crucially important for P. mirabilis infectivity and are required for biofilm formation and auto-aggregation, as well as for bladder and kidney colonization. Here, the X-ray crystal structure of the MR/P tip adhesin, MrpH, is reported. The structure has a fold not previously described and contains a transition metal center with Zn2+ coordinated by three conserved histidine residues and a ligand. Using biofilm assays, chelation, metal complementation, and site-directed mutagenesis of the three histidines, we show that an intact metal binding site occupied by zinc is essential for MR/P fimbria-mediated biofilm formation, and furthermore, that P. mirabilis biofilm formation is reversible in a zinc-dependent manner. Zinc is also required for MR/P-dependent agglutination of erythrocytes, and mutation of the metal binding site renders P. mirabilis unfit in a mouse model of UTI. The studies presented here provide important clues as to the mechanism of MR/P-mediated biofilm formation and serve as a starting point for identifying the physiological MR/P fimbrial receptor.


Assuntos
Adesinas Bacterianas/metabolismo , Biofilmes , Proteínas de Fímbrias/metabolismo , Proteus mirabilis/metabolismo , Infecções Urinárias/microbiologia , Zinco/metabolismo , Adesinas Bacterianas/química , Adesinas Bacterianas/genética , Sequência de Aminoácidos , Proteínas de Fímbrias/química , Proteínas de Fímbrias/genética , Humanos , Infecções por Proteus/metabolismo , Infecções por Proteus/microbiologia , Proteus mirabilis/química , Proteus mirabilis/genética , Alinhamento de Sequência , Infecções Urinárias/metabolismo , Zinco/química
8.
BMC Infect Dis ; 20(1): 453, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600258

RESUMO

INTRODUCTION: Uropathogenic E. coli is the leading cause of Urinary tract infections (UTIs), contributing to 80-90% of all community-acquired and 30-50% of all hospital-acquired UTIs. Biofilm forming Uropathogenic E. coli are associated with persistent and chronic inflammation leading to complicated and or recurrent UTIs. Biofilms provide an environment for poor antibiotic penetration and horizontal transfer of virulence genes which favors the development of Multidrug-resistant organisms (MDRO). Understanding biofilm formation and antimicrobial resistance determinants of Uropathogenic E. coli strains will provide insight into the development of treatment options for biofilm-associated UTIs. The aim of this study was to determine the biofilm forming capability, presence of virulence genes and antimicrobial susceptibility pattern of Uropathogenic E. coli isolates in Uganda. METHODS: This was a cross-sectional study carried in the Clinical Microbiology and Molecular biology laboratories at the Department of Medical Microbiology, Makerere University College of Health Sciences. We randomly selected 200 Uropathogenic E. coli clinical isolates among the stored isolates collected between January 2018 and December 2018 that had significant bacteriuria (> 105 CFU). All isolates were subjected to biofilm detection using the Congo Red Agar method and Antimicrobial susceptibility testing was performed using the Kirby disk diffusion method. The isolates were later subjected PCR for the detection of Urovirulence genes namely; Pap, Fim, Sfa, Afa, Hly and Cnf, using commercially designed primers. RESULTS: In this study, 62.5% (125/200) were positive biofilm formers and 78% (156/200) of these were multi-drug resistant (MDR). The isolates were most resistant to Trimethoprim sulphamethoxazole and Amoxicillin (93%) followed by gentamycin (87%) and the least was imipenem (0.5%). Fim was the most prevalent Urovirulence gene (53.5%) followed by Pap (21%), Sfa (13%), Afa (8%), Cnf (5.5%) and Hyl (0%). CONCLUSIONS: We demonstrate a high prevalence of biofilm-forming Uropathogenic E. coli strains that are highly associated with the MDR phenotype. We recommend routine surveillance of antimicrobial resistance and biofilm formation to understand the antibiotics suitable in the management of biofilm-associated UTIs.


Assuntos
Antibacterianos/uso terapêutico , Biofilmes/crescimento & desenvolvimento , Infecções por Escherichia coli/epidemiologia , Infecções Urinárias/epidemiologia , Escherichia coli Uropatogênica/genética , Escherichia coli Uropatogênica/patogenicidade , Estudos Transversais , Farmacorresistência Bacteriana Múltipla/genética , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/microbiologia , Humanos , Testes de Sensibilidade Microbiana , Fenótipo , Reação em Cadeia da Polimerase , Prevalência , Uganda/epidemiologia , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia , Escherichia coli Uropatogênica/efeitos dos fármacos , Escherichia coli Uropatogênica/isolamento & purificação , Virulência/genética , Fatores de Virulência/genética
9.
BMC Infect Dis ; 20(1): 452, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32600270

RESUMO

BACKGROUND: Bacterial infections are the most frequent complications in patients with malignancy, and the epidemiology of nosocomial infections among cancer patients has changed over time. This study aimed to evaluate the characteristics, antibiotic resistance patterns, and prognosis of nosocomial infections due to multidrug-resistant (MDR) bacteria in cancer patients. METHODS: This retrospective observational study analyzed cancer patients with nosocomial infections caused by MDR from August 2013 to May 2019. The extracted clinical data were recorded in a standardized form and compared based on the survival status of the patients after infection and during hospitalization. The data were analyzed using independent samples t-test, Chi-square test, and binary logistic regression. P-values < 0.05 were considered significant. RESULTS: One thousand eight patients developed nosocomial infections during hospitalization, with MDR strains detected in 257 patients. Urinary tract infection (38.1%), respiratory tract infection (26.8%), and bloodstream infection (BSI) (12.5%) were the most common infection types. Extended-spectrum ß-lactamase producing Enterobacteriaceae (ESBL-PE) (72.8%) members were the most frequently isolated MDR strains, followed by Acinetobacter baumannii (11.7%), and Stenotrophomonas maltophilia (6.2%). The results of multivariate regression analysis revealed that smoking history, intrapleural/abdominal infusion history within 30 days, the presence of an indwelling urinary catheter, length of hospitalization, and hemoglobin were independent factors for in-hospital mortality in the study population. The isolated MDR bacteria exhibited high rates of sensitivity to amikacin, meropenem, and imipenem. CONCLUSIONS: The burden of nosocomial infections due to MDR bacteria is considerably high in oncological patients, with ESBL-PE being the most predominant causative pathogen. Our findings suggest that amikacin and carbapenems actively against more than 89.7% of MDR isolates. The precise management of MDR bacterial infections in cancer patients may improve the prognosis of these individuals.


Assuntos
Antibacterianos/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Infecções por Enterobacteriaceae/tratamento farmacológico , Infecções por Enterobacteriaceae/epidemiologia , Enterobacteriaceae/efeitos dos fármacos , Neoplasias/microbiologia , Idoso , Antibacterianos/farmacologia , China/epidemiologia , Infecção Hospitalar/microbiologia , Infecção Hospitalar/mortalidade , Enterobacteriaceae/isolamento & purificação , Infecções por Enterobacteriaceae/microbiologia , Infecções por Enterobacteriaceae/mortalidade , Feminino , Mortalidade Hospitalar , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/mortalidade , Prevalência , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia
11.
Eur J Clin Microbiol Infect Dis ; 39(10): 1971-1981, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32557326

RESUMO

The purpose of this study is to collect information on the bacterial resistance to antibiotics of bacteria isolated from urine cultures of patients treated for upper urinary tract calculi. Data of patients with urinary tract infection and urolithiasis were retrospectively reviewed to collect information on age, gender, stone size, location, hydronephrosis, procedure of stone removal and antibiotic treatment, identification and susceptibility of pathogens, symptoms, and infectious complications. A total of 912 patients from 11 centers in 7 countries (Bulgaria, Greece, Italy, North Macedonia, Spain, and Turkey) were studied. Mean age was 54 ± 16 years and M/F ratio 322/590. Out of 946 microbial isolates, the most common were E. coli, Gram-positive, KES group (Klebsiella, Enterobacter, Serratia), Proteus spp., and P. aeruginosa. Carbapenems, piperacillin/tazobactam and amikacin showed low resistance rates to E. coli (2.5%, 7%, and 3.6%) and Proteus spp. (7.7%, 16%, and 7.4%), but higher rates were observed with Klebsiella spp., P. aeruginosa, and Gram-positive. Fosfomycin had resistance rates less than 10% to E. coli, 23% to KES group, and 19% to Gram-positive. Amoxicillin/clavulanate, cephalosporins, quinolones, and TMP/SMX showed high resistance rates to most bacterial strains. High rates of antibiotic resistance were observed in patients candidate to stone treatment from South-Eastern Europe. The empirical use of antibiotics with low resistance rates should be reserved to the most serious cases to avoid the increase of multidrug resistant bacteria. Basing on our results, carbapenems, piperacillin/tazobactam, and amikacin may be a possible option for empiric treatment of urinary stone patients showing systemic symptoms.


Assuntos
Anti-Infecciosos/farmacologia , Bactérias/efeitos dos fármacos , Infecções Bacterianas/microbiologia , Infecções Urinárias/microbiologia , Urolitíase/microbiologia , Adulto , Idoso , Anti-Infecciosos/uso terapêutico , Bactérias/isolamento & purificação , Infecções Bacterianas/tratamento farmacológico , Europa (Continente) , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecções Urinárias/tratamento farmacológico , Urolitíase/tratamento farmacológico
12.
Nat Commun ; 11(1): 3184, 2020 06 23.
Artigo em Inglês | MEDLINE | ID: mdl-32576824

RESUMO

Peptide antibiotics are an abundant and synthetically tractable source of molecular diversity, but they are often cationic and can be cytotoxic, nephrotoxic and/or ototoxic, which has limited their clinical development. Here we report structure-guided optimization of an amphipathic peptide, arenicin-3, originally isolated from the marine lugworm Arenicola marina. The peptide induces bacterial membrane permeability and ATP release, with serial passaging resulting in a mutation in mlaC, a phospholipid transport gene. Structure-based design led to AA139, an antibiotic with broad-spectrum in vitro activity against multidrug-resistant and extensively drug-resistant bacteria, including ESBL, carbapenem- and colistin-resistant clinical isolates. The antibiotic induces a 3-4 log reduction in bacterial burden in mouse models of peritonitis, pneumonia and urinary tract infection. Cytotoxicity and haemolysis of the progenitor peptide is ameliorated with AA139, and the 'no observable adverse effect level' (NOAEL) dose in mice is ~10-fold greater than the dose generally required for efficacy in the infection models.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Animais , Carbapenêmicos/farmacologia , Permeabilidade da Membrana Celular/efeitos dos fármacos , Colistina/farmacologia , Modelos Animais de Doenças , Descoberta de Drogas , Feminino , Proteínas de Helminto/química , Proteínas de Helminto/farmacologia , Humanos , Masculino , Camundongos , Testes de Sensibilidade Microbiana , Peritonite/tratamento farmacológico , Peritonite/microbiologia , Pneumonia/tratamento farmacológico , Pneumonia/microbiologia , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia
13.
Am J Med Sci ; 360(3): 243-247, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32482350

RESUMO

BACKGROUND: It is unclear if parenteral cephalosporin treatment is appropriate in stable elderly patients hospitalized with a urinary tract infection (UTI) in settings with a high prevalence of bacterial resistant organisms. METHODS: We selected 934 consecutive stable patients aged ≥65 years with a UTI, 94.4% (n = 882) treated with a parenteral cephalosporin. Patients were divided into those with and without bacterial resistance to initial antibiotic therapy (BRIAT). Outcome measures were response to antibiotic therapy at 72 hours, prolonged hospitalization (>5 days) and mortality. RESULTS: There were 316 patients (33.8%) with BRIAT. At 72 hours, 33.9% (107/316) did not respond to initial treatment. The odds of a prolonged hospitalization was 2.1 (95% confidence interval-1.6-2.9), but no patient with BRIAT died from urosepsis (0%, 95% confidence interval-0-1.2%). CONCLUSIONS: In elderly stable patients hospitalized with a UTI, treatment with a parenteral cephalosporin might be appropriate despite a high prevalence of resistant organisms.


Assuntos
Antibacterianos , Resistência às Cefalosporinas , Cefalosporinas/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Infecções por Enterobacteriaceae/tratamento farmacológico , Feminino , Hospitalização , Humanos , Tempo de Internação , Masculino , Estudos Retrospectivos , Resultado do Tratamento , Infecções Urinárias/microbiologia , Infecções Urinárias/mortalidade , beta-Lactamases/biossíntese
14.
J Pediatr ; 224: 150-152, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32565095

RESUMO

This is a single-center US case series of 18 infants <90 days old who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). These infants had a mild febrile illness without significant pulmonary disease. One-half of the infants were hospitalized; 1 had bacterial urinary tract co-infection. Nasopharyngeal viral loads were notably high. Latinx ethnicity was overrepresented.


Assuntos
Infecções por Coronavirus/diagnóstico , Febre/diagnóstico , Pneumonia Viral/diagnóstico , Betacoronavirus , Chicago , Técnicas de Laboratório Clínico , Feminino , Febre/virologia , Hospitalização , Humanos , Lactente , Masculino , Pandemias , Admissão do Paciente , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Testes Sorológicos , Infecções Urinárias/complicações , Infecções Urinárias/microbiologia , Carga Viral
15.
Nat Commun ; 11(1): 2803, 2020 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-32499566

RESUMO

Host-associated reservoirs account for the majority of recurrent and oftentimes recalcitrant infections. Previous studies established that uropathogenic E. coli - the primary cause of urinary tract infections (UTIs) - can adhere to vaginal epithelial cells preceding UTI. Here, we demonstrate that diverse urinary E. coli isolates not only adhere to, but also invade vaginal cells. Intracellular colonization of the vaginal epithelium is detected in acute and chronic murine UTI models indicating the ability of E. coli to reside in the vagina following UTI. Conversely, in a vaginal colonization model, E. coli are detected inside vaginal cells and the urinary tract, indicating that vaginal colonization can seed the bladder. More critically, bacteria are identified inside vaginal cells from clinical samples from women with a history of recurrent UTI. These findings suggest that E. coli can establish a vaginal intracellular reservoir, where it may reside safely from extracellular stressors prior to causing an ascending infection.


Assuntos
Células Epiteliais/microbiologia , Escherichia coli Uropatogênica/patogenicidade , Vagina/microbiologia , Animais , Aderência Bacteriana , Infecções por Escherichia coli/microbiologia , Feminino , Camundongos , Camundongos Endogâmicos C3H , Microscopia de Fluorescência , Fagocitose , Bexiga Urinária/microbiologia , Sistema Urinário/microbiologia , Infecções Urinárias/microbiologia , Vagina/citologia
16.
Biofouling ; 36(3): 351-367, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32401555

RESUMO

Pseudomonas aeruginosa and Serratia marcescens are prominent members belonging to the group of ESKAPE pathogens responsible for Urinary Tract Infections (UTI) and nosocomial infections. Both the pathogens regulate several virulence factors, including biofilm formation through quorum sensing (QS), an intercellular communication mechanism. The present study describes the anti-biofilm and QS quenching effect of thiazolinyl-picolinamide based palladium(II) complexes against P. aeruginosa and S. marcescens. Palladium(II) complexes showed quorum sensing inhibitory potential in inhibiting swarming motility behaviour, pyocyanin production and other QS mediated virulence factors in both P. aeruginosa and S. marcescens. In addition, the establishment of biofilms was prevented on palladium (II) coated catheters. Overall, the present study demonstrates that thiazolinyl-picolinamide based palladium (II) complexes will be a promising strategy to combat device-mediated UTI infections.


Assuntos
Antibacterianos/farmacologia , Biofilmes/efeitos dos fármacos , Complexos de Coordenação/farmacologia , Paládio/farmacologia , Ácidos Picolínicos/química , Tiazóis/química , Cateteres Urinários/microbiologia , Antibacterianos/química , Antibacterianos/toxicidade , Biofilmes/crescimento & desenvolvimento , Sobrevivência Celular/efeitos dos fármacos , Complexos de Coordenação/química , Complexos de Coordenação/toxicidade , Infecção Hospitalar/prevenção & controle , Humanos , Células MCF-7 , Paládio/química , Paládio/toxicidade , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/metabolismo , Piocianina/metabolismo , Percepção de Quorum/efeitos dos fármacos , Serratia marcescens/efeitos dos fármacos , Serratia marcescens/metabolismo , Infecções Urinárias/microbiologia , Infecções Urinárias/prevenção & controle , Virulência , Fatores de Virulência/metabolismo
17.
PLoS One ; 15(5): e0232903, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32407346

RESUMO

BACKGROUND: Recent UK antibiotic stewardship policies have resulted in significant changes in primary care dispensing, but whether this has impacted antimicrobial resistance is unknown. AIM: To evaluate associations between changes in primary care dispensing and antimicrobial resistance in community-acquired urinary Escherichia coli infections. METHODS: Multilevel logistic regression modelling investigating relationships between primary care practice level antibiotic dispensing for approximately 1.5 million patients in South West England and resistance in 152,704 community-acquired urinary E. coli between 2013 and 2016. Relationships presented for within and subsequent quarter drug-bug pairs, adjusted for patient age, deprivation, and rurality. RESULTS: In line with national trends, overall antibiotic dispensing per 1000 registered patients fell 11%. Amoxicillin fell 14%, cefalexin 20%, ciprofloxacin 24%, co-amoxiclav 49% and trimethoprim 8%. Nitrofurantoin increased 7%. Antibiotic reductions were associated with reduced within quarter same-antibiotic resistance to: amoxicillin, ciprofloxacin and trimethoprim. Subsequent quarter reduced resistance was observed for trimethoprim and amoxicillin. Antibiotic dispensing reductions were associated with increased within and subsequent quarter resistance to cefalexin and co-amoxiclav. Increased nitrofurantoin dispensing was associated with reduced within and subsequent quarter trimethoprim resistance without affecting nitrofurantoin resistance. CONCLUSIONS: This evaluation of a national primary care stewardship policy on antimicrobial resistance in the community suggests both hoped-for benefits and unexpected harms. Some increase in resistance to cefalexin and co-amoxiclav could result from residual confounding. Randomised controlled trials are urgently required to investigate causality.


Assuntos
Antibacterianos/administração & dosagem , Gestão de Antimicrobianos/legislação & jurisprudência , Prescrições de Medicamentos/normas , Farmacorresistência Bacteriana/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Escherichia coli/efeitos dos fármacos , Infecções Urinárias/tratamento farmacológico , Adolescente , Adulto , Criança , Pré-Escolar , Uso de Medicamentos , Inglaterra/epidemiologia , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Padrões de Prática Médica/normas , Atenção Primária à Saúde/métodos , Atenção Primária à Saúde/normas , Infecções Urinárias/epidemiologia , Infecções Urinárias/microbiologia , Adulto Jovem
18.
Am J Physiol Renal Physiol ; 318(6): F1441-F1453, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32390512

RESUMO

Carbonic anhydrase II knockout (Car2-/-) mice have depleted numbers of renal intercalated cells, which are increasingly recognized to be innate immune effectors. We compared pyelonephritis susceptibility following reciprocal renal transplantations between Car2-/- and wild-type mice. We examined the effect of pharmacological CA suppression using acetazolamide in an experimental murine model of urinary tract infection. Car2-/- versus wild-type mice were compared for differences in renal innate immunity. In our transplant scheme, mice lacking CA-II in the kidney had increased pyelonephritis risk. Mice treated with acetazolamide had lower kidney bacterial burdens at 6 h postinfection, which appeared to be due to tubular flow from diuresis because comparable results were obtained when furosemide was substituted for acetazolamide. Isolated Car2-/- kidney cells enriched for intercalated cells demonstrated altered intercalated cell innate immune gene expression, notably increased calgizzarin and insulin receptor expression. Intercalated cell number and function along with renal tubular flow are determinants of pyelonephritis risk.


Assuntos
Acetazolamida/farmacologia , Anidrase Carbônica II/deficiência , Inibidores da Anidrase Carbônica/farmacologia , Infecções por Escherichia coli/prevenção & controle , Rim/efeitos dos fármacos , Pielonefrite/prevenção & controle , Infecções Urinárias/prevenção & controle , Acidose/enzimologia , Acidose/genética , Animais , Anidrase Carbônica II/antagonistas & inibidores , Anidrase Carbônica II/genética , Modelos Animais de Doenças , Infecções por Escherichia coli/enzimologia , Infecções por Escherichia coli/genética , Infecções por Escherichia coli/microbiologia , Regulação da Expressão Gênica no Desenvolvimento , Predisposição Genética para Doença , Imunidade Inata , Rim/enzimologia , Rim/imunologia , Rim/microbiologia , Transplante de Rim , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pielonefrite/enzimologia , Pielonefrite/genética , Pielonefrite/microbiologia , Receptor de Insulina/genética , Receptor de Insulina/metabolismo , Proteínas S100/genética , Proteínas S100/metabolismo , Infecções Urinárias/enzimologia , Infecções Urinárias/genética , Infecções Urinárias/microbiologia , Escherichia coli Uropatogênica/patogenicidade
19.
Nat Immunol ; 21(6): 671-683, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32424366

RESUMO

Urinary tract infections (UTIs) typically evoke prompt and vigorous innate bladder immune responses, including extensive exfoliation of the epithelium. To explain the basis for the extraordinarily high recurrence rates of UTIs, we examined adaptive immune responses in mouse bladders. We found that, following each bladder infection, a highly T helper type 2 (TH2)-skewed immune response directed at bladder re-epithelialization is observed, with limited capacity to clear infection. This response is initiated by a distinct subset of CD301b+OX40L+ dendritic cells, which migrate into the bladder epithelium after infection before trafficking to lymph nodes to preferentially activate TH2 cells. The bladder epithelial repair response is cumulative and aberrant as, after multiple infections, the epithelium was markedly thickened and bladder capacity was reduced relative to controls. Thus, recurrence of UTIs and associated bladder dysfunction are the outcome of the preferential focus of the adaptive immune response on epithelial repair at the expense of bacterial clearance.


Assuntos
Cistite/etiologia , Cistite/metabolismo , Ativação Linfocitária/imunologia , Membrana Mucosa/imunologia , Membrana Mucosa/metabolismo , Células Th2/imunologia , Células Th2/metabolismo , Animais , Carga Bacteriana , Biomarcadores , Linhagem Celular , Cistite/patologia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Camundongos , Camundongos Knockout , Membrana Mucosa/patologia , Células Th1/imunologia , Células Th1/metabolismo , Células Th1/patologia , Infecções Urinárias/etiologia , Infecções Urinárias/metabolismo , Infecções Urinárias/microbiologia , Cicatrização/genética , Cicatrização/imunologia
20.
Medicine (Baltimore) ; 99(19): e19960, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32384444

RESUMO

OBJECTIVES: This meta-analysis assessed the efficacy and safety of novel ß-lactam/ß-lactamase inhibitor combinations in the treatment of complicated urinary tract infection (cUTI)/acute pyelonephritis (APN). METHODS: PubMed, Web of Science, EBSCO (Elton B. Stephens Co.), Cochrane Library, Ovid MEDLINE, and Embase databases were accessed until November 21, 2019. In this meta-analysis, only randomized controlled trials comparing the treatment efficacy of novel ß-lactam/ß-lactamase inhibitor combinations with other antibiotics for cUTI/APN in adult patients were included. The outcomes included the clinical and microbiological responses, and risk of adverse events (AEs). RESULTS: Overall, the experimental group treated with a novel ß-lactam/ß-lactamase inhibitor combination and the control group comprised 1346 and 1376 patients, respectively. No significant difference in the clinical response rate at test-of-cure was observed between the novel ß-lactam/ß-lactamase inhibitor combination and comparators among the microbiological modified intent-to-treat population (89.1% vs 88.3%, OR, 1.04; 95% confidence interval [CI], 0.76-1.42; I = 28%) and the microbiologically evaluable population (95.2% vs 94.7%, OR, 1.12; 95% CI, 0.68-1.84; I = 0%). Additionally, the novel ß-lactam/ß-lactamase inhibitor combination was associated with a better microbiological response at test-of-cure than the comparators among the microbiological modified intent-to-treat population (74.4% vs 68.5%, OR, 1.34; 95% CI, 1.04-1.72; I = 45%) and microbiologically evaluable population (80.1% vs 72.5%, OR, 1.49; 95% CI, 1.06-2.10; I = 58%). Finally, the risk of AEs associated with the novel ß-lactam/ß-lactamase inhibitor combination was similar to that associated with the comparators (treatment-emergent adverse events [TEAE], OR, 1.04; 95% CI, 0.87-1.23; I = 19%; serious AEs, OR, 1.21; 95% CI, 0.82-1.76; I = 0%; treatment discontinuation for drug-related TEAE, OR, 077; 95% CI, 0.38-1.56, I = 5%). The all-cause mortality did not differ between the novel ß-lactam/ß-lactamase inhibitor combination and comparators (OR, 1.19; 95% CI, 0.37-3.81; I = 0%). CONCLUSIONS: The clinical and microbiological responses of novel ß-lactam/ß-lactamase inhibitor combinations in the treatment of cUTI/APN are similar to those of other available antibiotics. These combinations also share a safety profile similar to that of other antibiotics.


Assuntos
Pielonefrite , Infecções Urinárias , Inibidores de beta-Lactamases/farmacologia , beta-Lactamas/antagonistas & inibidores , Antibacterianos/farmacologia , Quimioterapia Combinada/métodos , Humanos , Pielonefrite/tratamento farmacológico , Pielonefrite/microbiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Infecções Urinárias/tratamento farmacológico , Infecções Urinárias/microbiologia
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