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1.
Mayo Clin Proc ; 95(12): 2699-2703, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33276841

RESUMO

Approval by the US Food and Drug Administration (FDA) of a drug for a given indication is thought to reassure clinicians, other health care providers, and patients that substantial evidence of effectiveness exists for specific indicated populations (patients and diseases). This study examines whether FDA approval of certain antibiotics should be so reassuring for all patient populations identified in the FDA-approved labels. Specifically, this study compared patient populations covered by FDA-approved labels for 21 novel antibiotics approved between 1999 and 2018 to the patient exclusion and inclusion criteria of pivotal trials that supported those approvals. We found that every FDA-approved label for these antibiotics included at least one identifiable patient population that was explicitly excluded from enrolling in the supporting pivotal trials. Two antibiotics, bedaquiline and ceftazidime-avibactam, were approved for use in populations that were fully excluded from enrolling in registration trials.


Assuntos
Antibacterianos , Infecções Bacterianas , Aprovação de Drogas , Definição da Elegibilidade , Seleção de Pacientes , Adulto , Antibacterianos/classificação , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Tomada de Decisão Clínica , Ensaios Clínicos como Assunto , Aprovação de Drogas/métodos , Aprovação de Drogas/estatística & dados numéricos , Definição da Elegibilidade/métodos , Definição da Elegibilidade/organização & administração , Feminino , Humanos , Masculino , Padrões de Prática Médica , Vigilância de Produtos Comercializados/normas , Estados Unidos
2.
J S Afr Vet Assoc ; 91(0): e1-e6, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-33054249

RESUMO

Although Pseudomonas aeruginosa (P. aeruginosa) can infect both animals and humans, there is a paucity of veterinary studies on antimicrobial resistance of P. aeruginosa in South Africa. Secondary data of canine clinical cases presented at the hospital from January 2007 to December 2013 was used. The following information was recorded: type of sample, the date of sampling and the antimicrobial susceptibility results. Frequencies, proportions and their 95% confidence intervals were calculated for all the categorical variables. In total, 155 P. aeruginosa isolates were identified and included in this study. All the isolates were resistant to at least one antimicrobial (AMR), while 92% were multi-drug resistant (MDR). Most isolates were resistant to lincomycin (98%), penicillin-G (96%), orbifloxacin (90%), trimethoprim-sulfamethoxazole (90%) and doxycycline (87%). A low proportion of isolates was resistant to imipenem (6%), tobramycin (12%), amikacin (16%) and gentamicin (18%). A high proportion of MDR-P. aeruginosa isolates was resistant to amoxycillin-clavulanic acid (99%), tylosin (99%), chloramphenicol (97%) and doxycycline (96%). Few (6%) of MDR-P. aeruginosa isolates were resistant to imipenem. Pseudomonas aeruginosa was associated with infections of various organ systems in this study. All P. aeruginosa isolates of P. aeruginosa exhibited resistance to ß-lactams, fluoroquinolones and lincosamides. Clinicians at the hospital in question should consider these findings when treating infections associated with P. aeruginosa.


Assuntos
Doenças do Cão/microbiologia , Farmacorresistência Bacteriana Múltipla , Infecções por Pseudomonas/veterinária , Pseudomonas aeruginosa/efeitos dos fármacos , Centros Médicos Acadêmicos , Animais , Antibacterianos/classificação , Antibacterianos/farmacologia , Cães , Hospitais Veterinários , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/fisiologia , África do Sul
3.
Zhong Nan Da Xue Xue Bao Yi Xue Ban ; 45(5): 571-575, 2020 May 28.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32879109

RESUMO

OBJECTIVES: To explore the prescribing habits of doctors, and to provide basis for rational use of antibiotics in clinical practice via investigating and analyzing the applications of antibiotics in treatment of coronavirus disease 2019 (COVID-19) in the designated hospital. METHODS: Specification, quantity, amount, defined daily dose system (DDDs), defined daily dose consumption (DDDc), antibiotics use density (AUD), composition, frequency of use, combined use of antibacterial drugs used in the hospital were analyzed between Feb. 2020 and Mar. 2020. RESULTS: A total of 25 antibiotic drugs in 12 categories were used. The total cost for antibiotic drugs was 1 million 238 thousand yuan, in which quinolone accounts for 48%, the third generation cephalosporin/lactamase inhibitors accounts for 15.86%, antifungals accounts for 14.17%, oxazolidone accounts for 13.46%, and carbapenms account for 12.73%. The top three drugs of DDDs and AUD were moxifloxacin hydrochloride tablets, moxifloxacin hydrochloride and sodium chloride injection, cefoperazone sodium and sulbactam sodium for injection. The proportion of patients who had been used more than two kinds of antibiotics was 22.36%. CONCLUSIONS: Broad-spectrum, high-potency antibiotics are used at the beginning of COVID-19 treatment. The varieties of antibiotics meet the requirements of the management of antibiotics, and the utilization rate of antibiotics and the cost proportion of antibiotics in COVID-19 patients are within a reasonable range.In the future, for the treatment of COVID-19, we should continue to summarize the experience, improve the strategies, and rationally apply antibiotics on the basis of guidelines.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Antibacterianos/classificação , Betacoronavirus , Humanos , Pandemias
4.
Nature ; 586(7827): 145-150, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32968273

RESUMO

Natural products serve as chemical blueprints for most antibiotics in clinical use. The evolutionary process by which these molecules arise is inherently accompanied by the co-evolution of resistance mechanisms that shorten the clinical lifetime of any given class of antibiotics1. Virginiamycin acetyltransferase (Vat) enzymes are resistance proteins that provide protection against streptogramins2, potent antibiotics against Gram-positive bacteria that inhibit the bacterial ribosome3. Owing to the challenge of selectively modifying the chemically complex, 23-membered macrocyclic scaffold of group A streptogramins, analogues that overcome the resistance conferred by Vat enzymes have not been previously developed2. Here we report the design, synthesis, and antibacterial evaluation of group A streptogramin antibiotics with extensive structural variability. Using cryo-electron microscopy and forcefield-based refinement, we characterize the binding of eight analogues to the bacterial ribosome at high resolution, revealing binding interactions that extend into the peptidyl tRNA-binding site and towards synergistic binders that occupy the nascent peptide exit tunnel. One of these analogues has excellent activity against several streptogramin-resistant strains of Staphylococcus aureus, exhibits decreased rates of acetylation in vitro, and is effective at lowering bacterial load in a mouse model of infection. Our results demonstrate that the combination of rational design and modular chemical synthesis can revitalize classes of antibiotics that are limited by naturally arising resistance mechanisms.


Assuntos
Antibacterianos/síntese química , Antibacterianos/farmacologia , Desenho de Fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Estreptogramina Grupo A/síntese química , Estreptogramina Grupo A/farmacologia , Acetilação/efeitos dos fármacos , Acetiltransferases/genética , Acetiltransferases/metabolismo , Animais , Antibacterianos/classificação , Carga Bacteriana/efeitos dos fármacos , Sítios de Ligação , Microscopia Crioeletrônica , Feminino , Técnicas In Vitro , Camundongos , Testes de Sensibilidade Microbiana , Modelos Moleculares , RNA de Transferência/metabolismo , Ribossomos/efeitos dos fármacos , Ribossomos/metabolismo , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/genética , Staphylococcus aureus/metabolismo , Estreptogramina Grupo A/química , Estreptogramina Grupo A/classificação , Virginiamicina/análogos & derivados , Virginiamicina/química , Virginiamicina/metabolismo
5.
Lancet Gastroenterol Hepatol ; 5(11): 986-995, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32818437

RESUMO

BACKGROUND: Use of antibiotics in early life has been linked with childhood inflammatory bowel disease (IBD), but data for adults are mixed, and based on smaller investigations that did not compare risk among siblings with shared genetic or environmental risk factors. We aimed to investigate the association between antibiotic therapy and IBD in a large, population-based study. METHODS: In this prospective case-control study, we identified people living in Sweden aged 16 years or older, with a diagnosis of IBD based on histology and at least one diagnosis code for IBD or its subtypes (ulcerative colitis and Crohn's disease). We identified consecutive patients with incident IBD from the ESPRESSO (Epidemiology Strengthened by histoPathology Reports in Sweden) study, cross-referenced with the Swedish Patient Register and the Prescribed Drug Register. We accrued data for cumulative antibiotic dispensations until 1 year before time of matching for patients and up to five general population controls per patient (matched on the basis of age, sex, county, and calendar year). We also included unaffected full siblings as a secondary control group. Conditional logistic regression was used to estimate multivariable-adjusted odds ratios (aORs) and 95% CIs for diagnosis of incident IBD. FINDINGS: We identified 23 982 new patients with IBD (15 951 ulcerative colitis, 7898 Crohn's disease, 133 unclassified IBD) diagnosed between Jan 1, 2007, and Dec 31, 2016. 117 827 matched controls and 28 732 siblings were also identified. After adjusting for several risk factors, aOR in patients who had used antibiotics versus those who had never used antibiotics was 1·88 (95% CI 1·79-1·98) for diagnosis of incident IBD, 1·74 (1·64-1·85) for ulcerative colitis, and 2·27 (2·06-2·49) for Crohn's disease. aOR was higher in patients who had received one antibiotic dispensation (1·11, 1·07-1·15), two antibiotic dispensations (1·38, 1·32-1·44), and three or more antibiotic dispensations (1·55, 1·49-1·61) than patients who had none. Increased risk was noted for ulcerative colitis (aOR with three or more antibiotic dispensations 1·47, 95% CI 1·40-1·54) and Crohn's disease (1·64, 1·53-1·76) with higher estimates corresponding to broad-spectrum antibiotics. Similar but attenuated results were observed when siblings were used as the reference group, with an aOR of 1·35 (95% CI 1·28-1·43) for patients who had received three or more dispensations, compared with general population controls. INTERPRETATION: Higher cumulative exposure to systemic antibiotic therapy, particularly treatments with greater spectrum of microbial coverage, may be associated with a greater risk of new-onset IBD and its subtypes. The association between antimicrobial treatment and IBD did not appear to differ when predisposed siblings were used as the reference controls. Our findings, if substantiated by longer-term prospective studies in humans or mechanistic preclinical investigations, suggest the need to further emphasise antibiotic stewardship to prevent the rise in dysbiosis-related chronic diseases, including IBD. FUNDING: National Institutes of Health. Crohn's and Colitis Foundation.


Assuntos
Antibacterianos , Disbiose , Doenças Inflamatórias Intestinais , Adolescente , Adulto , Idade de Início , Antibacterianos/classificação , Antibacterianos/uso terapêutico , Gestão de Antimicrobianos , Biópsia/estatística & dados numéricos , Estudos de Casos e Controles , Sistemas de Informação em Farmácia Clínica/estatística & dados numéricos , Disbiose/induzido quimicamente , Disbiose/prevenção & controle , Feminino , Humanos , Doenças Inflamatórias Intestinais/epidemiologia , Doenças Inflamatórias Intestinais/patologia , Masculino , Estudos Prospectivos , Medição de Risco/métodos , Fatores de Risco , Irmãos , Suécia/epidemiologia
6.
Lancet Infect Dis ; 20(10): 1172-1181, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32505231

RESUMO

BACKGROUND: Evidence-based needs assessments for novel antibiotics against highly-resistant Gram-negative infections (GNIs) are scarce. We aimed to use real-world data from an electronic health record repository to identify treatment opportunities in US hospitals for GNIs resistant to all first-line drugs. METHODS: For this retrospective cohort study, population estimates with an unmet need for novel Gram-negative antibiotics were quantified using the Cerner Health Facts database (2009-15), aggregating episodes of infection in US hospitals with pathogens displaying difficult-to-treat resistance (DTR; resistance to carbapenems, other ß-lactams, and fluoroquinolones) and episodes involving empirical coverage with reserve drugs (colistin or polymyxin B and aminoglycosides). Episodes displaying extended-spectrum cephalosporin resistance (ECR) were also estimated. Episodes were multiplied by site-specific and fixed 14-day treatment durations for conservative and liberal days-of-therapy (DOT) estimates and stratified by site and taxon. Hospital type-specific DOT rates were reliability adjusted to account for random variation; cluster analyses quantified contribution from outbreaks. FINDINGS: Across 2 996 271 inpatient encounters and 134 hospitals, there were 1352 DTR-GNI episodes, 1765 episodes involving empirical therapy with colistin or polymyxin B, and 16 632 episodes involving aminoglycosides. Collectively, these yielded 39·0 (conservative estimate) to 138·2 (liberal estimate) DOT per 10 000 encounters for a novel DTR-GNI-targeted drug, whereas greater treatment opportunities were identified for ECR (six times greater) and ß-lactam susceptible GNIs (70 times greater). The most common DTR-GNI site and pathogen was lower respiratory (14·3 [43·3%] of 33 DOT per 10 000 encounters) and Pseudomonas aeruginosa (522 [38·1%] of 1371 episodes), whereas Enterobacteriaceae urinary-tract infections dominated the ECR or carbapenem-sparing niche (59·0% [5589 of 9535 episodes]) equating to 210·7 DOT per 10 000 encounters. DTR Stenotrophomonas maltophilia, Burkholderia spp, and Achromobacter spp represented less than 1 DOT per 10 000 encounters each. The estimated need for DTR-GNI-targeted antibiotics saw minor contributions by outbreaks and varied from 0·5 to 73·1 DOT per 10 000 encounters by hospital type. INTERPRETATION: Suspected or documented GNIs with no or suboptimal treatment options are relatively infrequent. Non-revenue-based strategies and innovative trial designs are probably essential to the development of antibiotics with improved effectiveness for these GNIs. FUNDING: Center for Drug Evaluation and Research, US Food and Drug Administration; Intramural Research Program, National Institutes of Health Clinical Center and the National Institute of Allergy and Infectious Diseases and the National Cancer Institute.


Assuntos
Antibacterianos/uso terapêutico , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Antibacterianos/classificação , Estudos de Coortes , Surtos de Doenças , Infecções por Bactérias Gram-Negativas/epidemiologia , Hospitais , Humanos , Pacientes Internados , Testes de Sensibilidade Microbiana , Determinação de Necessidades de Cuidados de Saúde , Estudos Retrospectivos , Estados Unidos/epidemiologia
7.
Postgrad Med ; 132(6): 526-531, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32379557

RESUMO

Background: Streptococcal Toxic Shock Syndrome (STSS) is a serious condition that can arise from streptococcal postpartum endometritis. It is associated with a substantial increase in mortality rate and can rarely result in multiorgan infarction. Early recognition plays a vital role in patients' outcome. Objective: To report a case of complicated STSS and review the literature for previous case reports of streptococcal postpartum endometritis to determine if STSS diagnostic criteria (published by the Centers for Disease Control and Prevention) were fulfilled. Case presentation: This is a 41-year-old woman who presented 5 days after an uncomplicated vaginal delivery with endometritis complicated by invasive group A ß-hemolytic streptococcus (GAS) infection and confirmed toxic shock syndrome. The patient was initially admitted to the critical care unit due to hemodynamic compromise requiring intravenous (IV) fluids, IV antibiotic therapy with penicillin and clindamycin, and IV immunoglobulin therapy. The patient subsequently developed multi-organ infarctions, acute respiratory distress syndrome requiring noninvasive respiratory support, and severe reactive arthritis. Literature review revealed 15 case reports of GAS postpartum endometritis, five met criteria for confirmed STSS. One patient died from severe septic shock leading to cardiopulmonary arrest. Thirteen out of 15 cases of postpartum endometritis occurred after uncomplicated vaginal delivery. Conclusion: STSS is a serious and possibly fatal medical condition that requires early diagnosis and treatment to prevent poor patient outcomes and death. Careful consideration to the patient's postpartum clinical presentation with the implementation of an intradisciplinary approach should be utilized.


Assuntos
Antibacterianos , Artrite Reativa , Endometrite , Rim , Infecção Puerperal , Infarto do Baço/diagnóstico por imagem , Infecções Estreptocócicas , Streptococcus pyogenes/isolamento & purificação , Adulto , Antibacterianos/administração & dosagem , Antibacterianos/classificação , Artrite Reativa/etiologia , Artrite Reativa/terapia , Endometrite/microbiologia , Endometrite/fisiopatologia , Endometrite/terapia , Feminino , Hidratação/métodos , Humanos , Rim/irrigação sanguínea , Rim/diagnóstico por imagem , Oxigenoterapia/métodos , Infecção Puerperal/microbiologia , Infecção Puerperal/fisiopatologia , Infecção Puerperal/terapia , Síndrome do Desconforto Respiratório do Adulto/diagnóstico , Síndrome do Desconforto Respiratório do Adulto/terapia , Choque Séptico/microbiologia , Choque Séptico/fisiopatologia , Infecções Estreptocócicas/etiologia , Infecções Estreptocócicas/fisiopatologia , Infecções Estreptocócicas/terapia , Tomografia Computadorizada por Raios X/métodos , Resultado do Tratamento
8.
Rev Mal Respir ; 37(6): 443-450, 2020 Jun.
Artigo em Francês | MEDLINE | ID: mdl-32439250

RESUMO

INTRODUCTION: The evolution of the microbial epidemiology of pleuropulmonary infections complicating community-acquired pneumonia has resulted in a change in empirical or targeted antibiotic therapy in children in the post Prevenar 13 era. The three main pathogens involved in pleural empyema in children are Streptococcus pneumoniae, Staphylococcus aureus and group A Streptococcus. METHODS: A questionnaire according to the DELPHI method was sent to experts in the field (paediatric pulmonologists and infectious disease specialists) in France with the purpose of reaching a consensus on the conservative antibiotic treatment of pleural empyema in children. Two rounds were completed as part of this DELPHI process. RESULTS: Our work has shown that in the absence of clinical signs of severity, the prescription of an intravenous monotherapy is consensual but there is no agreement on the choice of drug to use. A consensus was also reached on treatment adjustment based on the results of blood cultures, the non-systematic use of a combination therapy, the need for continued oral therapy and the lack of impact of pleural drainage on infection control. On the other hand, after the second round of DELPHI, there was no consensus on the duration of intravenous antibiotic therapy and on the treatment of severe pleural empyema, especially when caused by Staphylococci. CONCLUSIONS: The result of this work highlights the needed for new French recommendations based on the evolution of microbial epidemiology in the post PCV13 era.


Assuntos
Antibacterianos/uso terapêutico , Técnica Delfos , Empiema Pleural/tratamento farmacológico , Empiema Pleural/epidemiologia , Pediatria , Idade de Início , Antibacterianos/classificação , Gestão de Antimicrobianos/métodos , Gestão de Antimicrobianos/normas , Criança , Consenso , Empiema Pleural/microbiologia , Prova Pericial/estatística & dados numéricos , Feminino , França/epidemiologia , Humanos , Masculino , Testes de Sensibilidade Microbiana/estatística & dados numéricos , Pediatria/métodos , Pediatria/normas , Derrame Pleural/tratamento farmacológico , Derrame Pleural/epidemiologia , Padrões de Prática Médica/estatística & dados numéricos , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologia , Infecções Respiratórias/terapia
9.
Postgrad Med ; 132(6): 512-520, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32281451

RESUMO

Objectives: Helicobacter pylori (H. pylori) infection caused by antibiotic-resistant strains represents a major public health threat that aggressively promotes gastric cancer progression. Antibiotic resistance evaluation is immensely important to counteract its emergence. Here we merely determine the prevalence of antibiotic resistance in H. pylori isolates and its correlation with cagA motifs and the homB gene. Methods: The antibiotic resistance pattern was investigated on 128 H. pylori isolated strains utilizing the disk diffusion method and study the correlation between it and the presence of pathogenic genes, cagA EPIYA motifs and homB gene, were accurately detected using the PCR. Results: The resistance rates to four antibiotics were 70.1% for metronidazole, 35.5% for amoxicillin, 7.2% for clarithromycin and 8.2% for tetracycline. Resistance phenotypes were separated into two groups, single resistance (63.2%) and multi-resistance (12.5%). The prevalence of cagA-ABCC resistant strains and homB+ resistant strains was significantly higher in cancer (p = 0.04 and p = 0.01, respectively) than those of other diseases. The prevalence of cagA-homB + resistance strains was 21.8% and had a significant correlation with PUD. A significant relationship was observed between amoxicillin resistant rate with ABC-homB (p = 0.0006). Conclusion: The Resistance rate to selected antibiotics in Shiraz is higher than years ago. The presence of cagA-homB + is associated with antibiotic resistance and also homB can be used as a marker to antibiotic resistance status prediction in H. pylori isolated in this area.


Assuntos
Antibacterianos , Antígenos de Bactérias/genética , Proteínas da Membrana Bacteriana Externa/genética , Proteínas de Bactérias/genética , Resistência Microbiana a Medicamentos/genética , Infecções por Helicobacter , Helicobacter pylori , Neoplasias Gástricas , Adulto , Antibacterianos/classificação , Antibacterianos/farmacologia , Feminino , Infecções por Helicobacter/tratamento farmacológico , Infecções por Helicobacter/epidemiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/genética , Helicobacter pylori/isolamento & purificação , Humanos , Irã (Geográfico)/epidemiologia , Masculino , Neoplasias Gástricas/epidemiologia , Neoplasias Gástricas/microbiologia , Neoplasias Gástricas/patologia
10.
Medicina (B Aires) ; 80(2): 185-188, 2020.
Artigo em Espanhol | MEDLINE | ID: mdl-32282329

RESUMO

Miasis is the infestation of man and animals by larvae of flies belonging to the order Diptera, suborder Cyclorrapha. Eighty percent of miasis in Argentina is caused by Cochliomyia hominivorax, a species that induces pronounced tissue invasion and destruction, and results in severe clinical forms. Because of the aggressiveness of its larvae, it is important to reach a specific etiological diagnosis. We present four cases of miasis by C. hominivorax in two patients living in the city of Buenos Aires but working in a rural area and two patients living in the Greater Buenos Aires.


Assuntos
Miíase/parasitologia , Idoso de 80 Anos ou mais , Animais , Antibacterianos/classificação , Antibacterianos/uso terapêutico , Antiparasitários/uso terapêutico , Argentina , Dípteros , Feminino , Humanos , Ivermectina/uso terapêutico , Larva , Masculino , Pessoa de Meia-Idade , Miíase/tratamento farmacológico , Miíase/etiologia , Toxoide Tetânico/uso terapêutico
11.
Pan Afr Med J ; 35: 12, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32341733

RESUMO

Introduction: Antibiotic misuse is the paramount factor for antibiotic resistance. Tamale Teaching Hospital (TTH), located in Ghana's Northern Region, is the biggest tertiary hospital in the Northern half of the country and consequently one of the biggest prescribers of antibiotics. Understanding the use of antibiotics in the TTH and providing information that could be inferred to develop strategies for antibiotic prescription is of extreme importance in this era of multiple and pan-resistant strains of pathogenic microorganisms. Methods: A cross-sectional study on the use of antibiotics at TTH in the Northern region of Ghana was performed. Data were collected by reviewing 10% of patients' files from January to June 2015 and then assessed for its appropriateness against the criteria based on the British National Formulary (BNF) 2015 and BNF children 2013-2014. Results were expressed in frequencies and percentages. Results: A total of 617 patients' records were included in this study. Up to 385 cases of different antibiotic misuse were found, comprising of 335 errors in prescriptions and 50 non-completed treatments. The most common prescription error was made on treatment duration (29.6%). The potential interactions were 16.7%. Conclusion: The study revealed a high burden of antibiotics misuse in TTH. This suggests a need for the development of an antibiotic stewardship programme for the hospital.


Assuntos
Antibacterianos/uso terapêutico , Padrões de Prática Médica/estatística & dados numéricos , Adulto , Antibacterianos/classificação , Gestão de Antimicrobianos/normas , Gestão de Antimicrobianos/estatística & dados numéricos , Criança , Estudos Transversais , Uso Indevido de Medicamentos/estatística & dados numéricos , Feminino , Gana/epidemiologia , Hospitais de Ensino/estatística & dados numéricos , Humanos , Pacientes Internados/estatística & dados numéricos , Masculino , Registros Médicos/estatística & dados numéricos , Erros de Medicação/estatística & dados numéricos , Mortalidade , Estudos Retrospectivos
12.
J Med Chem ; 63(16): 8849-8856, 2020 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-32191034

RESUMO

Machine learning techniques can be applied to MALDI-TOF mass spectral data of drug-treated cells to obtain classification models which assign the mechanism of action of drugs. Here, we present an example application of this concept to the screening of antibacterial drugs that act at the major bacterial target sites such as the ribosome, penicillin-binding proteins, and topoisomerases in a pharmacologically relevant phenotypic setting. We show that antibacterial effects can be identified and classified in a label-free, high-throughput manner using wild-type Escherichia coli and Staphylococcus aureus cells at variable levels of target engagement. This phenotypic approach, which combines mass spectrometry and machine learning, therefore denoted as PhenoMS-ML, may prove useful for the identification and development of novel antibacterial compounds and other pharmacological agents.


Assuntos
Antibacterianos/classificação , Aprendizado de Máquina , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/estatística & dados numéricos , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Staphylococcus aureus/efeitos dos fármacos
13.
PLoS One ; 15(2): e0228555, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32040513

RESUMO

Antimicrobial resistance is a growing global health concern. Antimicrobial stewardship (AMS) curbs resistance rates by encouraging rational antimicrobial use. However, data on antimicrobial stewardship in developing countries is scarce. The objective of this study was to characterize antimicrobial use at the University Teaching Hospital (UTH) in Lusaka, Zambia as a guiding step in the development of an AMS program. This was a cross-sectional, observational study evaluating antimicrobial appropriateness and consumption in non-critically ill adult medicine patients admitted to UTH. Appropriateness was defined as a composite measure based upon daily chart review. Sixty percent (88/146) of all adult patients admitted to the general wards had at least one antimicrobial ordered and were included in this study. The most commonly treated infectious diseases were tuberculosis, pneumonia, and septicemia. Treatment of drug sensitive tuberculosis is standardized in a four-drug combination pill of rifampicin, isoniazid, pyrazinamide and ethambutol, therefore appropriateness of therapy was not further evaluated. The most common antimicrobials ordered were cefotaxime (n = 45), ceftriaxone (n = 28), and metronidazole (n = 14). Overall, 67% of antimicrobial orders were inappropriately prescribed to some extent, largely driven by incorrect dose or frequency in patients with renal dysfunction. Antimicrobial prescribing among hospitalized patients at UTH is common and there is room for optimization of a majority of antimicrobial orders. Availability of certain antimicrobials must be taken into consideration during AMS program development.


Assuntos
Anti-Infecciosos/uso terapêutico , Gestão de Antimicrobianos , Doenças Transmissíveis/tratamento farmacológico , Doenças Transmissíveis/epidemiologia , Adulto , Antibacterianos/classificação , Antibacterianos/uso terapêutico , Anti-Infecciosos/classificação , Gestão de Antimicrobianos/organização & administração , Gestão de Antimicrobianos/normas , Gestão de Antimicrobianos/estatística & dados numéricos , Estudos Transversais , Feminino , Hospitalização/estatística & dados numéricos , Hospitais de Ensino/estatística & dados numéricos , Hospitais Universitários/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Farmácias/estatística & dados numéricos , Padrões de Prática Médica/normas , Padrões de Prática Médica/estatística & dados numéricos , Zâmbia/epidemiologia
14.
J Pediatr ; 220: 125-131.e5, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32093934

RESUMO

OBJECTIVES: To assess clinical indication-specific antibiotic prescribing in pediatric practice in China based on the World Health Organization (WHO) Access, Watch, and Reserve (AWaRe) metrics and to detect potential problem areas. STUDY DESIGN: Pediatric prescription records on the 16th of each month during 2018 were sampled for all encounters at outpatient and emergency departments of 16 tertiary care hospitals via hospital information systems. Antibiotic prescribing patterns were analyzed across and within diagnostic conditions according to WHO AWaRe metrics and Anatomical Therapeutic Chemical (ATC) classification. RESULTS: A total of 260 001 pediatric encounters were assessed, and antibiotics were prescribed in 94 453 (36.3%). In 35 167 encounters (37.2%), at least 1 intravenous antibiotic was administered. WHO Watch group antibiotics accounted for 82.2% (n = 84 176) of all antibiotic therapies. Azithromycin (n = 15 791; 15.4%) was the most commonly prescribed antibiotic, and third-generation cephalosporins (n = 44 387; 43.3%) were the most commonly prescribed antibiotic class. In at least 66 098 encounters (70.0%), antibiotics were prescribed for respiratory tract conditions, mainly for bronchitis/bronchiolitis (n = 25 815; 27.3%), upper respiratory tract infection (n = 25 184; 26.7%), and pneumonia (n = 13 392; 14.2%). CONCLUSIONS: Overuse and misuse of WHO Watch group antibiotics for respiratory tract conditions and viral infectious diseases is common in pediatric outpatients in China. Pediatric antimicrobial stewardship should be strengthened using WHO AWaRe metrics.


Assuntos
Antibacterianos/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Uso de Medicamentos/estatística & dados numéricos , Padrões de Prática Médica , Adolescente , Antibacterianos/classificação , Criança , Pré-Escolar , China , Estudos Transversais , Humanos , Lactente , Estudos Prospectivos , Organização Mundial da Saúde
16.
Biomed Res Int ; 2020: 5658212, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32076608

RESUMO

Dental caries is the most common oral disease. The bacteriological aetiology of dental caries promotes the use of antibiotics or antimicrobial agents to prevent this type of oral infectious disease. Antibiotics have been developed for more than 80 years since Fleming discovered penicillin in 1928, and systemic antibiotics have been used to treat dental caries for a long time. However, new types of antimicrobial agents have been developed to fight against dental caries. The purpose of this review is to focus on the application of systemic antibiotics and other antimicrobial agents with respect to their clinical use to date, including the history of their development, and their side effects, uses, structure types, and molecular mechanisms to promote a better understanding of the importance of microbial interactions in dental plaque and combinational treatments.


Assuntos
Antibacterianos/uso terapêutico , Cárie Dentária/tratamento farmacológico , Antibacterianos/classificação , Anti-Infecciosos/uso terapêutico , Placa Dentária/tratamento farmacológico , Placa Dentária/microbiologia , Resistência Microbiana a Medicamentos , Humanos , Interações Microbianas , Probióticos/uso terapêutico , Remineralização Dentária
17.
Rev Assoc Med Bras (1992) ; 66Suppl 1(Suppl 1): s37-s44, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31939534

RESUMO

Peritoneal dialysis (PD) is a renal replacement therapy based on infusing a sterile solution into the peritoneal cavity through a catheter and provides for the removal of solutes and water using the peritoneal membrane as the exchange surface. This solution, which is in close contact with the capillaries in the peritoneum, allows diffusion solute transport and osmotic ultrafiltration water loss since it is hyperosmolar to plasma due to the addition of osmotic agents (most commonly glucose). Infusion and drainage of the solution into the peritoneal cavity can be performed in two ways: manually (continuous ambulatory PD), in which the patient usually goes through four solution changes throughout the day, or machine-assisted PD (automated PD), in which dialysis is performed with the aid of a cycling machine that allows changes to be made overnight while the patient is sleeping. Prescription and follow-up of PD involve characterizing the type of peritoneal transport and assessing the offered dialysis dose (solute clearance) as well as diagnosing and treating possible method-related complications (infectious and non-infectious).


Assuntos
Falência Renal Crônica/terapia , Diálise Peritoneal/métodos , Antibacterianos/administração & dosagem , Antibacterianos/classificação , Soluções para Diálise/uso terapêutico , Humanos , Diálise Peritoneal Ambulatorial Contínua
18.
Appl Microbiol Biotechnol ; 104(5): 2217-2227, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31965221

RESUMO

Physically disrupting microorganism membranes to enable antibiotics to overcome resistance mechanisms that inhibit or excrete antibiotics has great potential for reducing antibiotic doses and rendering resistance mechanisms inert. We demonstrate the synergistic inactivation of a Gram-positive (Staphylococcus aureus) and two Gram-negative (Escherichia coli and Pseudomonas aeruginosa) bacteria by combining 222 30 kV/cm electric pulses (EPs) or 500 20 kV/cm EPs with 300-ns EP duration with various antibiotics with different mechanisms of action is demonstrated. Doses of antibiotics that produced no inactivation in 10 min of exposure in solution with bacteria induced several log reductions under the influence of nanosecond EPs. Combining 2 µg/L or 20 µg/mL of rifampicin with the 30 kV/cm EPs enhanced Staphylococcus aureus inactivation compared with EPs alone, while only a few of the other combinations demonstrated improvement. Combining 2 µg/L or 20 µg/mL of mupirocin or rifampicin with either EP train enhanced E. coli inactivation compared with EPs alone. Combining 2 µg/L or 20 µg/mL of erythromycin or vancomycin with the 30 kV/cm EPs enhanced E. coli inactivation compared with EPs alone. These results indicate that EPs can make Gram-positive antibiotics efficient for inactivating Gram-negative bacteria with future studies required to optimize EP parameters for other antibiotics and Gram-negative bacteria.


Assuntos
Antibacterianos/farmacologia , Eletricidade , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Antibacterianos/classificação , Relação Dose-Resposta a Droga , Reposicionamento de Medicamentos , Resistência Microbiana a Medicamentos , Viabilidade Microbiana
19.
PLoS One ; 15(1): e0220484, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31990938

RESUMO

The growing occurrence of multidrug-resistant (MDR) Salmonella enterica in poultry has been reported with public health concern worldwide. We reported, recently, the occurrence of Escherichia coli and Salmonella enterica serovars carrying clinically relevant resistance genes in dairy cattle farms in the Wakiso District, Uganda, highlighting an urgent need to monitor food-producing animal environments. Here, we present the prevalence, antimicrobial resistance, and sequence type of 51 Salmonella isolates recovered from 379 environmental samples from chicken farms in Uganda. Among the Salmonella isolates, 32/51 (62.7%) were resistant to at least one antimicrobial, and 10/51 (19.6%) displayed multiple drug resistance. Through PCR, five replicon plasmids were identified among chicken Salmonella isolates including IncFIIS 17/51 (33.3%), IncI1α 12/51 (23.5%), IncP 8/51 (15.7%), IncX1 8/51 (15.7%), and IncX2 1/51 (2.0%). In addition, we identified two additional replicons through WGS (Whole Genome Sequencing; ColpVC and IncFIB). A significant seasonal difference between chicken sampling periods was observed (p = 0.0017). We conclude that MDR Salmonella highlights the risks posed to animals and humans. Implementing a robust, integrated surveillance system will aid in monitoring MDR zoonotic threats.


Assuntos
Farmacorresistência Bacteriana Múltipla/genética , Genes Bacterianos , Plasmídeos/metabolismo , Doenças das Aves Domésticas/epidemiologia , Infecções por Salmonella/epidemiologia , Salmonella enterica/genética , Animais , Antibacterianos/classificação , Antibacterianos/farmacologia , Galinhas/microbiologia , Fazendas , Humanos , Vigilância Imunológica , Plasmídeos/química , Doenças das Aves Domésticas/microbiologia , Doenças das Aves Domésticas/transmissão , Prevalência , Replicon , Infecções por Salmonella/microbiologia , Infecções por Salmonella/transmissão , Salmonella enterica/efeitos dos fármacos , Salmonella enterica/isolamento & purificação , Estações do Ano , Uganda/epidemiologia , Sequenciamento Completo do Genoma
20.
Urology ; 137: 79-83, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31705946

RESUMO

OBJECTIVE: To investigate severe infectious complications after intravesical treatment with bacillus Calmette-Guérin (BCG). We examine a retrospective case series of 10 patients between 2006 and 2018 with severe cystitis or systemic infection after BCG. METHODS: Patients with BCG cystitis or disseminated infection were retrospectively identified between 2006 and 2018 at our institution. Cases were reviewed for bladder cancer treatments, demographics, treatment of infection, and outcomes. RESULTS: There was a 0.8% rate of severe BCG cystitis or disseminated infection. Seven patients experienced delayed-onset infections >3 months after last BCG instillation. Four had isolated bladder symptoms, and 5 had diverse systemic manifestations. One patient was asymptomatic and diagnosed on cystoscopic findings. All were treated with varied antibiotic regimens; 9 included antituberculous therapy, and 1 was treated with levofloxacin alone. Two underwent cystectomy for end-stage bladder. The remaining patients are asymptomatic with no residual effects. All are in remission for bladder cancer. CONCLUSION: Severe infectious complications after BCG are rare and thus difficult to study. Treatment regimens can vary widely. Thorough reporting of patient outcomes is essential to expand the limited body of knowledge.


Assuntos
Antibacterianos , Vacina BCG , Cistectomia/métodos , Cistite , Sepse , Neoplasias da Bexiga Urinária/terapia , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/efeitos adversos , Administração Intravesical , Idoso , Antibacterianos/administração & dosagem , Antibacterianos/classificação , Vacina BCG/administração & dosagem , Vacina BCG/efeitos adversos , Cistite/diagnóstico , Cistite/etiologia , Cistite/fisiopatologia , Cistite/terapia , Feminino , Humanos , Masculino , Avaliação de Processos e Resultados em Cuidados de Saúde , Estudos Retrospectivos , Sepse/diagnóstico , Sepse/etiologia , Sepse/fisiopatologia , Sepse/terapia , Índice de Gravidade de Doença
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