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1.
Ann Ist Super Sanita ; 56(3): 359-364, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32959802

RESUMO

Current literature shows that secondary bacterial infections, although less frequent than in previous influenza pandemics, affect COVID-19 patients. Mycoplasma pneumoniae, Staphylococcus aureus, Legionella pneumophila, Streptococcus pneumoniae, Haemophilus and Klebsiella spp. are the main species isolated. Of note, Mycobacterium tuberculosis-COVID-19 coinfections are also reported. However, bacterial coinfection rates increase in patients admitted in the intensive care units, and those diseases can be due to super-infections by nosocomial antibiotic-resistant bacteria. This highlights the urgency to revise frequent and empiric prescription of broad-spectrum antibiotics in COVID-19 patients, with more attention to evidence-based studies and respect for the antimicrobial stewardship principles.


Assuntos
Infecções Bacterianas/epidemiologia , Betacoronavirus , Coinfecção/epidemiologia , Infecções por Coronavirus/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Gestão de Antimicrobianos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Infecções Bacterianas/transmissão , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/transmissão , Resistência Microbiana a Medicamentos , Diagnóstico Precoce , Humanos , Unidades de Terapia Intensiva , Itália/epidemiologia , Micoses/epidemiologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/microbiologia , Especificidade da Espécie , Tuberculose/epidemiologia
2.
Anal Bioanal Chem ; 412(28): 7685-7699, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32870351

RESUMO

Pathogen-host cell interactions play an important role in many human infectious and inflammatory diseases. Several pathogens, including Escherichia coli (E. coli), Mycobacterium tuberculosis (M. tb), and even the recent 2019 novel coronavirus (2019-nCoV), can cause serious breathing and brain disorders, tissue injury and inflammation, leading to high rates of mortality and resulting in great loss to human physical and mental health as well as the global economy. These infectious diseases exploit the microbial and host factors to induce serious inflammatory and immunological symptoms. Thus the development of anti-inflammatory drugs targeting bacterial/viral infection is an urgent need. In previous studies, YojI-IFNAR2, YojI-IL10RA, YojI-NRP1,YojI-SIGLEC7, and YojI-MC4R membrane-protein interactions were found to mediate E. coli invasion of the blood-brain barrier (BBB), which activated the downstream anti-inflammatory proteins NACHT, LRR and PYD domains-containing protein 2(NLRP2), using a proteomic chip conjugated with cell immunofluorescence labeling. However, the studies of pathogen (bacteria/virus)-host cell interactions mediated by membrane protein interactions did not extend their principles to broad biomedical applications such as 2019-nCoV infectious disease therapy. The first part of this feature article presents in-depth analysis of the cross-talk of cellular anti-inflammatory transduction signaling among interferon membrane protein receptor II (IFNAR2), interleukin-10 receptor subunit alpha (IL-10RA), NLRP2 and [Ca2+]-dependent phospholipase A2 (PLA2G5), based on experimental results and important published studies, which lays a theoretical foundation for the high-throughput construction of the cytokine and virion solution chip. The paper then moves on to the construction of the novel GPCR recombinant herpes virion chip and virion nano-oscillators for profiling membrane protein functions, which drove the idea of constructing the new recombinant virion and cytokine liquid chips for HTS of leading drugs. Due to the different structural properties of GPCR, IFNAR2, ACE2 and Spike of 2019-nCoV, their ligands will either bind the extracellular domain of IFNAR2/ACE2/Spike or the specific loops of the GPCR on the envelope of the recombinant herpes virions to induce dynamic charge distribution changes that lead to the variable electron transition for detection. Taken together, the combined overview of two of the most innovative and exciting developments in the immunoinflammatory field provides new insight into high-throughput construction of ultrasensitive cytokine and virion liquid chips for HTS of anti-inflammatory drugs or clinical diagnosis and treatment of inflammatory diseases including infectious diseases, acute or chronic inflammation (acute gouty arthritis or rheumatoid arthritis), cardiovascular disease, atheromatosis, diabetes, obesity, tissue injury and tumors. It has significant value in the prevention and treatment of these serious and painful diseases. Graphical abstract.


Assuntos
Anti-Inflamatórios/farmacologia , Antivirais/farmacologia , Ensaios de Triagem em Larga Escala/instrumentação , Dispositivos Lab-On-A-Chip , Testes de Sensibilidade Microbiana/instrumentação , Animais , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/imunologia , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/imunologia , Citocinas/imunologia , Descoberta de Drogas/instrumentação , Descoberta de Drogas/métodos , Desenho de Equipamento , Ensaios de Triagem em Larga Escala/métodos , Humanos , Testes de Sensibilidade Microbiana/métodos , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/imunologia , Bibliotecas de Moléculas Pequenas/farmacologia , Vírion/efeitos dos fármacos , Vírion/imunologia , Viroses/tratamento farmacológico , Viroses/imunologia
3.
Maturitas ; 140: 49-54, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32972635

RESUMO

OBJECTIVE: To compare the effects of a 12-week course of 5%Pueraria mirifica gel and placebo gel on the prevalence of bacterial vaginosis, vaginal fungi, vaginal pH, vaginal health index (VHI), and genitourinary symptoms in postmenopausal women. STUDY DESIGN: In a randomized, double-blinded, placebo-controlled study (TCTR20160517002), 60 postmenopausal women were randomly assigned to a 12-week course of eitherP. mirifica gel or identical placebo gel. MAIN OUTCOME MEASURE: Vaginal Nugent score, fungal culture, pH, VHI, and genitourinary symptoms were evaluated at baseline and after 12 weeks of treatment. RESULTS: After 12 weeks of treatment, the proportion of participants with an abnormal Nugent score in the P. mirifica and the placebo groups were 6.7 % (2/30) and 23.3 % (7/30), respectively (p =  0.006). The mean changes in Nugent scores and VHI were significantly higher in the P. mirifica group (p <  0.05). There were no significant decreases in the prevalence of symptoms between the two groups after treatment (p > 0.05). CONCLUSION: A 12-week course of treatment with 5 % P. mirifica vaginal gel in postmenopausal women with GSM has been proved to be effective in reducing indicators of bacterial vaginosis compared with placebo gel. Nevertheless, the effect on alleviating genital symptoms was not demonstrated.


Assuntos
Infecções Bacterianas/tratamento farmacológico , Doenças Urogenitais Femininas/tratamento farmacológico , Micoses/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Pueraria , Método Duplo-Cego , Feminino , Humanos , Concentração de Íons de Hidrogênio , Pessoa de Meia-Idade , Fitoterapia , Pós-Menopausa , Síndrome , Vagina/química , Vagina/efeitos dos fármacos , Cremes, Espumas e Géis Vaginais/uso terapêutico
4.
Zhonghua Nei Ke Za Zhi ; 59(9): 706-710, 2020 Sep 01.
Artigo em Chinês | MEDLINE | ID: mdl-32838502

RESUMO

Objective: Long-term proton pump inhibitor(PPI) therapy may increase the risk of small intestinal bacterial overgrowth(SIBO). Few studies on the effect of on-demand and continuous PPI therapy are available in elderly. To investigate the prevalence of SIBO and the effect of on-demand and continuous PPI therapy on SIBO in elderly. Methods: A total of 200 elderly outpatients admitted to Department of Gastroenterology at the Second Medical Center of PLA General Hospital were enrolled and divided into 3 groups: continuous PPI group, on-demand PPI group and control group. SIBO was diagnosed according to methane and hydrogen lactulose breath test (LBT).The prevalence of SIBO in the 3 groups was analyzed. Results: The prevalence of SIBO was 71.5% in 200 elderly. PPI therapy and diabetes mellitus (DM) were independent risk factors for SIBO. The prevalence of SIBO was 77.1% (108/140) in elderly who underwent long-term PPI therapy and 58.3% (35/60) in those without PPI therapy (P<0.01).The prevalence of SIBO was significantly higher in continuous PPI therapy group than that in on-demand PPI group and control group(88.6% vs. 65.7% and 58.3%, all P<0.01).However, no significant difference was found in the prevalence of SIBO between on-demand PPI group and control group (P>0.05). In elderly who underwent long-term PPI therapy, the prevalence of SIBO increased significantly if administration time was longer than 61 months. Conclusions: SIBO usually occurs in elderly patients who receive continuous PPI rather than on-demand use. If elderly require long-term PPI therapy, on demand administration is suggested as long as primary diseases are properly treated.


Assuntos
Infecções Bacterianas , Inibidores da Bomba de Prótons/uso terapêutico , Idoso , Infecções Bacterianas/tratamento farmacológico , Testes Respiratórios , Humanos , Intestino Delgado , Lactulose
6.
Medicine (Baltimore) ; 99(34): e21860, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846837

RESUMO

BACKGROUND: The use of fluoroquinolone antibiotics has been restricted in children because of their potential to cause adverse musculoskeletal events. This study was performed to systematically evaluate whether there is a difference between fluoroquinolone and non-fluoroquinolone antibiotics in terms of their associated risk of adverse musculoskeletal events in children. METHODS: Cochrane Library, Embase, and PubMed databases were used to retrieve studies related to fluoroquinolone and non-fluoroquinolone-induced musculoskeletal adverse events in children. A meta-analysis was performed using Stata 11. RESULTS: A total of 10 studies were included in the analysis. The combined results showed that there was no statistical difference between fluoroquinolone and non-fluoroquinolone groups in terms of musculoskeletal adverse events in children (risk ratio = 1.145, 95% confidence interval = 0.974 - 1.345, P = .101). Subgroup analysis was performed using a random-effects model. Here, the effects on the trovafloxacin and levofloxacin groups were significantly different from that of the control group. However, musculoskeletal adverse events due to either drug was not reported after long-term follow-up. CONCLUSIONS: The results showed that fluoroquinolone and non-fluoroquinolone antibiotics were not different in terms of their ability to cause musculoskeletal adverse events in children. For this reason, fluoroquinolone antibiotics can be used in children as appropriate. PROSPERO REGISTRATION NUMBER: CRD42019133900.


Assuntos
Antibacterianos/efeitos adversos , Infecções Bacterianas/tratamento farmacológico , Fluoroquinolonas/efeitos adversos , Sistema Musculoesquelético/efeitos dos fármacos , Adolescente , Antibacterianos/uso terapêutico , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Fluoroquinolonas/uso terapêutico , Humanos , Lactente , Recém-Nascido , Levofloxacino/efeitos adversos , Levofloxacino/uso terapêutico , Masculino , Naftiridinas/efeitos adversos , Naftiridinas/uso terapêutico , Estudos Retrospectivos , Sensibilidade e Especificidade , Inibidores da Topoisomerase II/efeitos adversos , Inibidores da Topoisomerase II/uso terapêutico
7.
Appl Microbiol Biotechnol ; 104(18): 7777-7785, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32780290

RESUMO

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel ß-coronavirus, is the main pathogenic agent of the rapidly spreading pneumonia called coronavirus disease 2019 (COVID-19). SARS-CoV-2 infects much more people, especially the elder population, around the world than other coronavirus, such as SARS-CoV and MERS-CoV, which is challenging current global public health system. Beyond the pathogenesis of SARS-CoV-2, microbial coinfection plays an important role in the occurrence and development of SARS-CoV-2 infection by raising the difficulties of diagnosis, treatment, prognosis of COVID-19, and even increasing the disease symptom and mortality. We summarize the coinfection of virus, bacteria and fungi with SARS-CoV-2, their effects on COVID-19, the reasons of coinfection, and the diagnosis to emphasize the importance of microbial coinfection in COVID-19. KEY POINTS: • Microbial coinfection is a nonnegligible factor in COVID-19. • Microbial coinfection exacerbates the processes of the occurrence, development and prognosis of COVID-19, and the difficulties of clinical diagnosis and treatment. • Different virus, bacteria, and fungi contributed to the coinfection with SARS-CoV-2.


Assuntos
Infecções Bacterianas/epidemiologia , Infecções por Coronavirus/epidemiologia , Síndrome da Liberação de Citocina/epidemiologia , Linfopenia/epidemiologia , Micoses/epidemiologia , Pandemias , Pneumonia Viral/epidemiologia , Viroses/epidemiologia , Antibacterianos/uso terapêutico , Antivirais/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Infecções Bacterianas/virologia , Betacoronavirus/efeitos dos fármacos , Betacoronavirus/imunologia , Betacoronavirus/patogenicidade , Coinfecção , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/microbiologia , Infecções por Coronavirus/virologia , Síndrome da Liberação de Citocina/tratamento farmacológico , Síndrome da Liberação de Citocina/microbiologia , Síndrome da Liberação de Citocina/virologia , Citocinas/biossíntese , Progressão da Doença , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata/efeitos dos fármacos , Linfócitos/microbiologia , Linfócitos/virologia , Linfopenia/tratamento farmacológico , Linfopenia/microbiologia , Linfopenia/virologia , Micoses/tratamento farmacológico , Micoses/microbiologia , Micoses/virologia , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/microbiologia , Pneumonia Viral/virologia , Viroses/tratamento farmacológico , Viroses/microbiologia , Viroses/virologia
9.
PLoS One ; 15(8): e0236355, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32833993

RESUMO

INTRODUCTION: Neonatal infections are a common cause of death in India, but many families cannot access appropriate hospitals for its treatment due to various reasons. We implemented the World Health Organization PSBI management guideline when referral is not feasible within the public health system in Pune, India to evaluate feasibility, barriers and facilitators for its implementation. METHODS: A national-level consultative meeting between government officials and study partners resulted in a consensus on adaptation and implementation in four demonstration sites in selected states in India. At the state and district levels, similar meetings to plan the implementation strategy and roles were held between KEM Hospital Research Centre (KEMHRC) Pune and the public health system Pune, Maharashtra. The public health system was responsible for implementation of the intervention at eight tribal primary health centres (PHC) in Pune district, India, including delivering the intervention and ensuring supplies of all commodities while KEMHRC was responsible for technical support including training of health workers, assistance in PSBI identification and management, data collection and documentation of the implementation strategy. RESULTS: A total of 175 young infants with PSBI were identified and managed. Of these, 34 had critical illness (CI), 46 had clinical severe infection (CSI) and 10 were infants aged 0-6 days with fast breathing (FB) while 85 infants aged 7-59 days had fast breathing. Assuming a 10% incidence of PSBI among all live births, with 3071 live births recorded, the actual incidence of PSBI found in the study was 5.7%, resulting in an actual coverage was of 57%. Among the 90 infants with CI, CSI and FB in 0-6 days, who were advised referral to government tertiary care centre as per the PSBI guideline algorithm, 81 (90%) accepted referral while 9 (10%) refused and were offered treatment at primary health centres (PHC) with a seven-day course of injectable gentamicin and oral amoxicillin. All infants with FB in 7-59 days were offered treatment at PHCs as per the PSBI guideline algorithm with a seven-day course of oral amoxicillin. All except six infants who died and one with FB in 7-59 days, who was lost to follow-up, were successfully cured. Of the six who died, five had CSI and one had CI. Among the 81 infants with CI, CSI and FB in 0-6 days who accepted referral; 48(53%) were successfully referred to government tertiary facility while 33 (36.6%) preferred to visit a private tertiary health facility. The implementation strategy demonstrated a relatively high fidelity, acceptance and intervention penetration. Lack of training and confidence of the public health staff were major challenges faced, which were resolved to a large extent through supportive supervision and re-trainings. CONCLUSION: Management of PSBI is feasible to implement in out-patient facilities in the public health system, but technical support to the health system is required to jump-start the process. Fast breathing in 7-59 days old infants can be managed with oral amoxicillin without referral. A sustainable adoption of this intervention by the health system can lead to decrease in neonatal mortality and morbidity.


Assuntos
Amoxicilina/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Mortalidade Infantil , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/microbiologia , Estudos de Viabilidade , Feminino , Gentamicinas/uso terapêutico , Humanos , Índia/epidemiologia , Lactente , Recém-Nascido , Masculino , Grupos Populacionais , Organização Mundial da Saúde
10.
PLoS Med ; 17(8): e1003208, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32813708

RESUMO

BACKGROUND: The prescription rate of antibiotics is high for febrile children visiting the emergency department (ED), contributing to antimicrobial resistance. Large studies at European EDs covering diversity in antibiotic and broad-spectrum prescriptions in all febrile children are lacking. A better understanding of variability in antibiotic prescriptions in EDs and its relation with viral or bacterial disease is essential for the development and implementation of interventions to optimise antibiotic use. As part of the PERFORM (Personalised Risk assessment in Febrile illness to Optimise Real-life Management across the European Union) project, the MOFICHE (Management and Outcome of Fever in Children in Europe) study aims to investigate variation and appropriateness of antibiotic prescription in febrile children visiting EDs in Europe. METHODS AND FINDINGS: Between January 2017 and April 2018, data were prospectively collected on febrile children aged 0-18 years presenting to 12 EDs in 8 European countries (Austria, Germany, Greece, Latvia, the Netherlands [n = 3], Spain, Slovenia, United Kingdom [n = 3]). These EDs were based in university hospitals (n = 9) or large teaching hospitals (n = 3). Main outcomes were (1) antibiotic prescription rate; (2) the proportion of antibiotics that were broad-spectrum antibiotics; (3) the proportion of antibiotics of appropriate indication (presumed bacterial), inappropriate indication (presumed viral), or inconclusive indication (unknown bacterial/viral or other); (4) the proportion of oral antibiotics of inappropriate duration; and (5) the proportion of antibiotics that were guideline-concordant in uncomplicated urinary and upper and lower respiratory tract infections (RTIs). We determined variation of antibiotic prescription and broad-spectrum prescription by calculating standardised prescription rates using multilevel logistic regression and adjusted for general characteristics (e.g., age, sex, comorbidity, referral), disease severity (e.g., triage level, fever duration, presence of alarming signs), use and result of diagnostics, and focus and cause of infection. In this analysis of 35,650 children (median age 2.8 years, 55% male), overall antibiotic prescription rate was 31.9% (range across EDs: 22.4%-41.6%), and among those prescriptions, the broad-spectrum antibiotic prescription rate was 52.1% (range across EDs: 33.0%-90.3%). After standardisation, differences in antibiotic prescriptions ranged from 0.8 to 1.4, and the ratio between broad-spectrum and narrow-spectrum prescriptions ranged from 0.7 to 1.8 across EDs. Standardised antibiotic prescription rates varied for presumed bacterial infections (0.9 to 1.1), presumed viral infections (0.1 to 3.3), and infections of unknown cause (0.1 to 1.8). In all febrile children, antibiotic prescriptions were appropriate in 65.0% of prescriptions, inappropriate in 12.5% (range across EDs: 0.6%-29.3%), and inconclusive in 22.5% (range across EDs: 0.4%-60.8%). Prescriptions were of inappropriate duration in 20% of oral prescriptions (range across EDs: 4.4%-59.0%). Oral prescriptions were not concordant with the local guideline in 22.3% (range across EDs: 11.8%-47.3%) of prescriptions in uncomplicated RTIs and in 45.1% (range across EDs: 11.1%-100%) of prescriptions in uncomplicated urinary tract infections. A limitation of our study is that the included EDs are not representative of all febrile children attending EDs in that country. CONCLUSIONS: In this study, we observed wide variation between European EDs in prescriptions of antibiotics and broad-spectrum antibiotics in febrile children. Overall, one-third of prescriptions were inappropriate or inconclusive, with marked variation between EDs. Until better diagnostics are available to accurately differentiate between bacterial and viral aetiologies, implementation of antimicrobial stewardship guidelines across Europe is necessary to limit antimicrobial resistance.


Assuntos
Antibacterianos/administração & dosagem , Prescrições de Medicamentos , Farmacorresistência Bacteriana/efeitos dos fármacos , Serviço Hospitalar de Emergência/tendências , Febre/tratamento farmacológico , Febre/epidemiologia , Adolescente , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Criança , Pré-Escolar , Prescrições de Medicamentos/normas , Farmacorresistência Bacteriana/fisiologia , Serviço Hospitalar de Emergência/normas , Europa (Continente)/epidemiologia , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Estudos Prospectivos
11.
BMC Infect Dis ; 20(1): 515, 2020 Jul 16.
Artigo em Inglês | MEDLINE | ID: mdl-32677903

RESUMO

BACKGROUND: Procalcitonin is an inflammatory biomarker that is sensitive for bacterial infections and a promising clinical decision aid in antimicrobial stewardship programs. However, there are few studies of physicians' experiences concerning the use of PCT. The objective of this study was to investigate whether hospital physicians' experience with procalcitonin after 18 months of use can inform the PCT implementation in antimicrobial stewardship programs. MATERIALS/METHODS: We deployed a qualitative approach using semi-structured interviews with 14 hospital physicians who had experience with procalcitonin in clinical practice. Interviews were audio-taped, transcribed verbatim and analysed using thematic analysis. RESULTS: Physicians reported a knowledge gap, which made them uncertain about the appropriate procalcitonin use, interpretation, and trustworthiness. Simultaneously, the physicians experienced procalcitonin as a useful clinical decision aid but emphasised that their clinical evaluation of the patient was the most important factor when deciding on antibiotic treatment. CONCLUSIONS: Procalcitonin was regarded a helpful clinical tool, but the physicians called for more knowledge about its appropriate uses. Active implementation of unambiguous procalcitonin algorithms and physician education may enhance the utility of the test as an antimicrobial stewardship adjunct.


Assuntos
Gestão de Antimicrobianos , Infecções Bacterianas/diagnóstico , Biomarcadores/sangue , Hospitais/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Pró-Calcitonina/sangue , Adulto , Idoso , Algoritmos , Antibacterianos/uso terapêutico , Gestão de Antimicrobianos/organização & administração , Gestão de Antimicrobianos/normas , Infecções Bacterianas/sangue , Infecções Bacterianas/tratamento farmacológico , Bioensaio/estatística & dados numéricos , Feminino , Fidelidade a Diretrizes/estatística & dados numéricos , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Médicos/normas , Médicos/estatística & dados numéricos , Padrões de Prática Médica/normas , Pró-Calcitonina/análise , Pesquisa Qualitativa , Inquéritos e Questionários
13.
Rev Chilena Infectol ; 37(1): 9-18, 2020 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-32730394

RESUMO

BACKGROUND: Antimicrobial Stewardship Programs (ASP) focus in the appropriate use of antimicrobials to improve clinical results and minimize risk of adverse events. AIMS: To compare consumption and costs of antimicrobials before and after the establishment of an antimicrobial stewardship program and to describe the resistance proportion of priority bacteria. METHODS: Quasi-experimental, retrospective and prospective, descriptive and analytical study, to compare consumption and costs of antimicrobials in a pre- intervention period (2007-2010) and a post- intervention period (2011-2017). Additionally, a descriptive analysis of bacterial resistance from 2010 was performed. RESULTS: Gentamicin, vancomycin, meropenem, cefotaxime, ceftazidime and imipenem consumption decreased significantly in the post-intervention period compared to the pre-intervention period (p < 0.05) while consumption of amikacin, piperacillin/tazobactam, cefepime and levofloxacin increased significantly in the post-intervention period. The reduction in costs was not significant for gentamicin, vancomycin, meropenem, cefotaxime, ceftazidime and imipenem, meanwhile, costs increased for amikacin, piperacillin/tazobactam, cefepime and levofloxacin, but this was not significant. The isolation of Acinetobacter baumannii, Klebsiella pneumoniae, Staphylococcus aureus and Enterococcus faecalis decreased during the post-intervention period. CONCLUSION: The ASP showed a decrease in consumption and costs of some antimicrobials.


Assuntos
Antibacterianos , Gestão de Antimicrobianos , Infecções Bacterianas , Serviços Preventivos de Saúde , Antibacterianos/economia , Antibacterianos/uso terapêutico , Gestão de Antimicrobianos/economia , Gestão de Antimicrobianos/normas , Gestão de Antimicrobianos/estatística & dados numéricos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/prevenção & controle , Criança , Hospitais Pediátricos/economia , Hospitais Pediátricos/estatística & dados numéricos , Humanos , Testes de Sensibilidade Microbiana , Panamá , Serviços Preventivos de Saúde/economia , Serviços Preventivos de Saúde/normas , Serviços Preventivos de Saúde/estatística & dados numéricos , Estudos Prospectivos , Estudos Retrospectivos
14.
Rev Chilena Infectol ; 37(1): 19-22, 2020 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-32730395

RESUMO

BACKGROUND: Vancomycin has been considered the treatment of choice especially for methicillin-resistant Staphylococcus aureus (MRSA) infections; but its poor tissue penetration, renal toxicity, and requiring of dosages monitoring, raises the need for new treatment alternatives such as daptomycin. AIMS: To analyze the safety and effectiveness of daptomycin in children. METHODS: Children with microbiologically documented infections treated with daptomycin were retrospectively included. RESULTS: The most frequent infections were endocarditis in 9 (32%), sepsis in 4 (14%), bacteremia in 7 (associated with catheter in 3) (25%), osteomyelitis in 3 (10%), peritonitis associated with dialysis in 3 (10%) and suppurative thrombophlebitis in 2 patients (p) (7%). Methicillin-resistant Staphylococcus aureus was the most common pathogen in 18 patients (64%). The indications for daptomycin were due to the failure of conventional treatment in 17 (61%), and the toxicity or intolerance to vancomycin in 11 patients (39%). The average duration of treatment was 19 days (95% ICR 7-42 days). Four patients (14%) completed outpatient treatment, 22 patients had a favorable response (79%). Adverse events were reported in 3 patients (2 creatinine-phosfo-kinase increase) and in one severe skin rash. CONCLUSIONS: Daptomycin demonstrated a favorable efficacy and safety in this pediatric population.


Assuntos
Daptomicina , Hospitais Pediátricos , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Criança , Daptomicina/uso terapêutico , Hospitais Pediátricos/estatística & dados numéricos , Humanos , Estudos Retrospectivos , Resultado do Tratamento
15.
Proc Natl Acad Sci U S A ; 117(32): 19446-19454, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32723829

RESUMO

Antimicrobial peptides are important candidates for developing new classes of antibiotics because of their potency against antibiotic-resistant pathogens. Current research focuses on topical applications and it is unclear how to design peptides with systemic efficacy. To address this problem, we designed two potent peptides by combining database-guided discovery with structure-based design. When bound to membranes, these two short peptides with an identical amino acid composition can adopt two distinct amphipathic structures: A classic horizontal helix (horine) and a novel vertical spiral structure (verine). Their horizontal and vertical orientations on membranes were determined by solid-state 15N NMR data. While horine was potent primarily against gram-positive pathogens, verine showed broad-spectrum antimicrobial activity. Both peptides protected greater than 80% mice from infection-caused deaths. Moreover, horine and verine also displayed significant systemic efficacy in different murine models comparable to conventional antibiotics. In addition, they could eliminate resistant pathogens and preformed biofilms. Significantly, the peptides showed no nephrotoxicity to mice after intraperitoneal or intravenous administration for 1 wk. Our study underscores the significance of horine and verine in fighting drug-resistant pathogens.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Peptídeos Catiônicos Antimicrobianos/química , Peptídeos Catiônicos Antimicrobianos/farmacologia , Sequência de Aminoácidos , Animais , Antibacterianos/metabolismo , Antibacterianos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/metabolismo , Peptídeos Catiônicos Antimicrobianos/uso terapêutico , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Infecções Bacterianas/tratamento farmacológico , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Membrana Celular/metabolismo , Bases de Dados de Proteínas , Desenho de Fármacos , Farmacorresistência Bacteriana/efeitos dos fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Testes de Sensibilidade Microbiana , Relação Estrutura-Atividade , Resultado do Tratamento
16.
JAMA ; 324(1): 47-56, 2020 07 07.
Artigo em Inglês | MEDLINE | ID: mdl-32633801

RESUMO

Importance: Probiotics are frequently used by residents in care homes (residential homes or nursing homes that provide residents with 24-hour support for personal care or nursing care), although the evidence on whether probiotics prevent infections and reduce antibiotic use in these settings is limited. Objective: To determine whether a daily oral probiotic combination of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp lactis BB-12 compared with placebo reduces antibiotic administration in care home residents. Design, Setting, and Participants: Placebo-controlled randomized clinical trial of 310 care home residents, aged 65 years and older, recruited from 23 care homes in the United Kingdom between December 2016 and May 2018, with last follow-up on October 31, 2018. Interventions: Study participants were randomized to receive a daily capsule containing a probiotic combination of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp lactis BB-12 (total cell count per capsule, 1.3 × 1010 to 1.6 × 1010) (n = 155), or daily matched placebo (n = 155), for up to 1 year. Main Outcomes and Measures: The primary outcome was cumulative antibiotic administration days for all-cause infections measured from randomization for up to 1 year. Results: Among 310 randomized care home residents (mean age, 85.3 years; 66.8% women), 195 (62.9%) remained alive and completed the trial. Participant diary data (daily data including study product use, antibiotic administration, and signs of infection) were available for 98.7% randomized to the probiotic group and 97.4% randomized to placebo. Care home residents randomized to the probiotic group had a mean of 12.9 cumulative systemic antibiotic administration days (95% CI, 0 to 18.05), and residents randomized to placebo had a mean of 12.0 days (95% CI, 0 to 16.95) (absolute difference, 0.9 days [95% CI, -3.25 to 5.05]; adjusted incidence rate ratio, 1.13 [95% CI, 0.79 to 1.63]; P = .50). A total of 120 care home residents experienced 283 adverse events (150 adverse events in the probiotic group and 133 in the placebo group). Hospitalizations accounted for 94 of the events in probiotic group and 78 events in the placebo group, and deaths accounted for 33 of the events in the probiotic group and 32 of the events in the placebo group. Conclusions and Relevance: Among care home residents in the United Kingdom, a daily dose of a probiotic combination of Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp lactis BB-12 did not significantly reduce antibiotic administration for all-cause infections. These findings do not support the use of probiotics in this setting. Trial Registration: ISRCTN Identifier:16392920.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Bifidobacterium animalis , Uso de Medicamentos/estatística & dados numéricos , Lactobacillus rhamnosus , Probióticos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Moradias Assistidas , Infecções Bacterianas/prevenção & controle , Bifidobacterium animalis/isolamento & purificação , Método Duplo-Cego , Fezes/microbiologia , Feminino , Humanos , Lactobacillus rhamnosus/isolamento & purificação , Masculino , Casas de Saúde , Reino Unido
17.
Surg Clin North Am ; 100(4): 757-776, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32681875

RESUMO

This review of the literature concerning bacteria, antibiotics and tissue repair shows there are extensive data supporting microbial interference with wound healing once bacterial burden exceeds 104 CFU per unit of measure, The mechanism of bacterial interference lies largely in prolonging the inflammatory phase of tissue repair. Reducing the microbial bioburden allows tissue repair to continue. Systemic and topical antimicrobials appear critical to reducing the bioburden and facilitating repair. The current controversy over the use of antimicrobials in patients with chronically infected wounds, in particular, revolves around the definition of infection. The reliance on classic clinical signs of inflammation to support antimicrobial use in these patients is tenuous due to the lack of correlation of these signs with the microbial burden known to impair tissue repair.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Cicatrização/fisiologia , Infecção dos Ferimentos/tratamento farmacológico , Infecções Bacterianas/fisiopatologia , Carga Bacteriana/fisiologia , Biofilmes , Hipóxia Celular/fisiologia , Humanos , Neutrófilos/fisiologia , Infecção dos Ferimentos/fisiopatologia
19.
Cochrane Database Syst Rev ; 7: CD008037, 2020 07 16.
Artigo em Inglês | MEDLINE | ID: mdl-32671834

RESUMO

BACKGROUND: Cystic fibrosis is a multi-system disease characterised by the production of thick secretions causing recurrent pulmonary infection, often with unusual bacteria. This leads to lung destruction and eventually death through respiratory failure. There are no antibiotics in development that exert a new mode of action and many of the current antibiotics are ineffective in eradicating the bacteria once chronic infection is established. Antibiotic adjuvants - therapies that act by rendering the organism more susceptible to attack by antibiotics or the host immune system, by rendering it less virulent or killing it by other means, would be a significant therapeutic advance. This is an update of a previously published review. OBJECTIVES: To determine if antibiotic adjuvants improve clinical and microbiological outcome of pulmonary infection in people with cystic fibrosis. SEARCH METHODS: We searched the Cystic Fibrosis Trials Register which is compiled from database searches, hand searches of appropriate journals and conference proceedings. Date of most recent search: 16 January 2020. We also searched MEDLINE (all years) on 14 February 2019 and ongoing trials registers on 06 April 2020. SELECTION CRITERIA: Randomised controlled trials and quasi-randomised controlled trials of a therapy exerting an antibiotic adjuvant mechanism of action compared to placebo or no therapy for people with cystic fibrosis. DATA COLLECTION AND ANALYSIS: Two of the authors independently assessed and extracted data from identified trials. MAIN RESULTS: We identified 42 trials of which eight (350 participants) that examined antibiotic adjuvant therapies are included. Two further trials are ongoing and five are awaiting classification. The included trials assessed ß-carotene (one trial, 24 participants), garlic (one trial, 34 participants), KB001-A (a monoclonal antibody) (two trials, 196 participants), nitric oxide (two trials, 30 participants) and zinc supplementation (two trials, 66 participants). The zinc trials recruited children only, whereas the remaining trials recruited both adults and children. Three trials were located in Europe, one in Asia and four in the USA. Three of the interventions measured our primary outcome of pulmonary exacerbations (ß-carotene, mean difference (MD) -8.00 (95% confidence interval (CI) -18.78 to 2.78); KB001-A, risk ratio (RR) 0.25 (95% CI 0.03 to 2.40); zinc supplementation, RR 1.85 (95% CI 0.65 to 5.26). ß-carotene and KB001-A may make little or no difference to the number of exacerbations experienced (low-quality evidence); whereas, given the moderate-quality evidence we found that zinc probably makes no difference to this outcome. Respiratory function was measured in all of the included trials. ß-carotene and nitric oxide may make little or no difference to forced expiratory volume in one second (FEV1) (low-quality evidence), whilst garlic probably makes little or no difference to FEV1 (moderate-quality evidence). It is uncertain whether zinc or KB001-A improve FEV1 as the certainty of this evidence is very low. Few adverse events were seen across all of the different interventions and the adverse events that were reported were mild or not treatment-related (quality of the evidence ranged from very low to moderate). One of the trials (169 participants) comparing KB001-A and placebo, reported on the time to the next course of antibiotics; results showed there is probably no difference between groups, HR 1.00 (95% CI 0.69 to 1.45) (moderate-quality evidence). Quality of life was only reported in the two KB001-A trials, which demonstrated that there may be little or no difference between KB001-A and placebo (low-quality evidence). Sputum microbiology was measured and reported for the trials of KB001-A and nitric oxide (four trials). There was very low-quality evidence of a numerical reduction in Pseudomonas aeruginosa density with KB001-A, but it was not significant. The two trials looking at the effects of nitric oxide reported significant reductions in Staphylococcus aureus and near-significant reductions in Pseudomonas aeruginosa, but the quality of this evidence is again very low. AUTHORS' CONCLUSIONS: We could not identify an antibiotic adjuvant therapy that we could recommend for treating of lung infection in people with cystic fibrosis. The emergence of increasingly resistant bacteria makes the reliance on antibiotics alone challenging for cystic fibrosis teams. There is a need to explore alternative strategies, such as the use of adjuvant therapies. Further research is required to provide future therapeutic options.


Assuntos
Antibacterianos/administração & dosagem , Infecções Bacterianas/tratamento farmacológico , Fibrose Cística/complicações , Pneumopatias/tratamento farmacológico , Adolescente , Adulto , Anticorpos Monoclonais/uso terapêutico , Infecções Bacterianas/microbiologia , Quimioterapia Adjuvante , Criança , Progressão da Doença , Alho , Humanos , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Pneumopatias/microbiologia , Óxido Nítrico/uso terapêutico , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa , Ensaios Clínicos Controlados Aleatórios como Assunto , Vitaminas/uso terapêutico , Adulto Jovem , Zinco/administração & dosagem , beta Caroteno/uso terapêutico
20.
Proc Natl Acad Sci U S A ; 117(32): 19168-19177, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32719135

RESUMO

The emergence of superbugs developing resistance to antibiotics and the resurgence of microbial infections have led scientists to start an antimicrobial arms race. In this context, we have previously identified an active RiPP, the Ruminococcin C1, naturally produced by Ruminococcus gnavus E1, a symbiont of the healthy human intestinal microbiota. This RiPP, subclassified as a sactipeptide, requires the host digestive system to become active against pathogenic Clostridia and multidrug-resistant strains. Here we report its unique compact structure on the basis of four intramolecular thioether bridges with reversed stereochemistry introduced posttranslationally by a specific radical-SAM sactisynthase. This structure confers to the Ruminococcin C1 important clinical properties including stability to digestive conditions and physicochemical treatments, a higher affinity for bacteria than simulated intestinal epithelium, a valuable activity at therapeutic doses on a range of clinical pathogens, mediated by energy resources disruption, and finally safety for human gut tissues.


Assuntos
Antibacterianos/química , Antibacterianos/farmacologia , Clostridiales/química , Peptídeos/química , Peptídeos/farmacologia , Antibacterianos/isolamento & purificação , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/microbiologia , Humanos , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Peptídeos/isolamento & purificação
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