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1.
Georgian Med News ; (311): 151-156, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33814410

RESUMEN

This study was aimed at investigating morphological and functional changes in the small intestine mucosal layer of mice with antibiotic-induced dysbiosis and following its correction with probiotics and enterosorbents. The study was carried out on BALB / c line white laboratory mice. Samples of the small intestine, liver, and spleen were taken to be processed for electron microscopy. To determine qualitative and quantitative composition of intestinal lumenal microbiome, animals' faeces were studied. Bacteria were isolated and identified by standard methods. This study has experimentally confirmed the ability of antibacterials to induce dysbiotic conditions in animals that are accompanied by significant shifts in the composition of normal microflora, manifested with cytodestructive disorders in the small intestinal epithelium. We have demonstrated the property of probiotics and, to a lesser extent, of sorbents to reduce the intensity and extension of cytodestructive disorders in the course of antibiotic-induced dysbiosis and to normalize the body immune responses that accompany the development of dysbiotic conditions.


Asunto(s)
Disbiosis , Probióticos , Animales , Antibacterianos/efectos adversos , Bacterias , Disbiosis/inducido químicamente , Mucosa Intestinal , Ratones
2.
Artículo en Chino | MEDLINE | ID: mdl-33794642

RESUMEN

Aminoglycoside antibiotics can cause irreversible hearing loss, but they are still widely used because of their low production cost and broad-spectrum effect on most infections. Although it has been studied for decades, the mechanism of aminoglycoside-induced deafness has not been fully elucidated. Since patients'individual susceptibility to aminoglycoside-ototoxicity varies considerably, it is necessary to identify high-risk patients. This review summarizes the genetic mutations linked to aminoglycoside-induced deafness, in order to provide reference for further prevention and treatment of aminoglycoside-induced deafness.


Asunto(s)
Sordera , Pérdida Auditiva Sensorineural , Aminoglicósidos/efectos adversos , Antibacterianos/efectos adversos , Sordera/inducido químicamente , Sordera/genética , Predisposición Genética a la Enfermedad , Humanos , ARN Ribosómico
3.
MMW Fortschr Med ; 163(Suppl 4): 19-26, 2021 04.
Artículo en Alemán | MEDLINE | ID: mdl-33844181

RESUMEN

BACKGROUND: Antibiotic-associated diarrhoea (AAD) is the most common intestinal side effect of an antibiotic therapy. Various probiotics or probiotic combinations are often used preventively while taking antibiotics for the prevention of AAD. METHOD: This review is based on a systematic literature research in MEDLINE and EMBASE. 7 probiotics are presented with regard to their effectiveness and evidence in the prevention of AAD. Only preparations classified by the World Gastroenerology Organization (WGO) with evidence levels 1-3 for the prevention of AAD were taken into account. 37 clinical studies, including 33 RCTs, were evaluated. RESULTS: Saccharomyces (S.) boulardii CNCM I-745 is the most extensively studied probiotic regarding the prevention of AAD. It has shown evidence-based efficacy in all patient groups (outpatients and hospitalized children and adults). Lactobacillus rhamnosus GG also has a good evidence regarding the prevention of AAD in children and outpatient adults. The other probiotics and probiotic combinations evaluated in the present study only show efficacy in hospitalized patients or only show very limited evidence regarding their efficacy in the prevention of AAD due to the underlying study design or the small number of patients. CONCLUSION: The effect of probiotics is strain-specific, no general statement can be made about the efficacy of probiotics in the prevention of AAD. In principle, it is advisable to select a probiotic with an evidence-based effect such as S. boulardii CNCM I-745 or Lactobacillus rhamnosus GG to prevent AAD.


Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Probióticos , Antibacterianos/efectos adversos , Niño , Diarrea/inducido químicamente , Diarrea/prevención & control , Humanos , Probióticos/uso terapéutico , Proyectos de Investigación
4.
Int J Mol Sci ; 22(6)2021 Mar 12.
Artículo en Inglés | MEDLINE | ID: mdl-33809032

RESUMEN

Iron is essential for multiple bacterial processes and is thus required for host colonization and infection. The antimicrobial activity of multiple iron chelators and gallium-based therapies against different bacterial species has been characterized in preclinical studies. In this review, we provide a synthesis of studies characterizing the antimicrobial activity of the major classes of iron chelators (hydroxamates, aminocarboxylates and hydroxypyridinones) and gallium compounds. Special emphasis is placed on recent in-vitro and in-vivo studies with the novel iron chelator DIBI. Limitations associated with iron chelation and gallium-based therapies are presented, with emphasis on limitations of preclinical models, lack of understanding regarding mechanisms of action, and potential host toxicity. Collectively, these studies demonstrate potential for iron chelators and gallium to be used as antimicrobial agents, particularly in combination with existing antibiotics. Additional studies are needed in order to characterize the activity of these compounds under physiologic conditions and address potential limitations associated with their clinical use as antimicrobial agents.


Asunto(s)
Infecciones Bacterianas/tratamiento farmacológico , Galio/uso terapéutico , Quelantes del Hierro/uso terapéutico , Hierro/metabolismo , Antibacterianos/efectos adversos , Antibacterianos/uso terapéutico , Bacterias/efectos de los fármacos , Bacterias/patogenicidad , Infecciones Bacterianas/microbiología , Farmacorresistencia Bacteriana , Humanos , Ácidos Hidroxámicos/química , Ácidos Hidroxámicos/uso terapéutico , Hierro/química , Quelantes del Hierro/química , Pruebas de Sensibilidad Microbiana
6.
Einstein (Sao Paulo) ; 19: eMD5703, 2021.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-33909756

RESUMEN

Betalactams are the most frequent cause of hypersensitivity reactions to drugs mediated by a specific immune mechanism. Immediate reactions occur within 1 to 6 hours after betalactam administration, and are generally IgE-mediated. They clinically translate into urticaria, angioedema and anaphylaxis. Non-immediate or delayed reactions occur after 1 hour of administration. These are the most common reactions and are usually mediated by T cells. The most frequent type is the maculopapular or morbilliform exanthematous eruption. Most individuals who report allergies to penicillin and betalactams can tolerate this group of antibiotics. To make diagnosis, a detailed medical history is essential to verify whether it was an immediate or non-immediate reaction. Thereafter, in vivo and/or in vitro tests for investigation may be performed. The challenging test is considered the gold standard method for diagnosis of betalactam hypersensitivity. The first approach when suspecting a reaction to betalactam is to discontinue exposure to the drug, and the only specific treatment is desensitization, which has very precise indications. The misdiagnosis of penicillin allergy affects the health system, since the "penicillin allergy" label is associated with increased bacterial resistance, higher rate of therapeutic failure, prolonged hospitalizations, readmissions, and increased costs. Thus, it is essential to develop strategies to assist the prescription of antibiotics in patients identified with a label of "betalactam allergy" at hospitals, and to enhance education of patients and their caregivers, as well as of non-specialist physicians.


Asunto(s)
Anafilaxia , Hipersensibilidad a las Drogas , Antibacterianos/efectos adversos , Hipersensibilidad a las Drogas/diagnóstico , Hipersensibilidad a las Drogas/etiología , Humanos , Penicilinas/efectos adversos , beta-Lactamas/efectos adversos
7.
BMC Infect Dis ; 21(1): 374, 2021 Apr 21.
Artículo en Inglés | MEDLINE | ID: mdl-33882843

RESUMEN

BACKGROUND: The emerging threat of antibiotic resistance is growing exponentially and antibiotic stewardship programs are cornerstone to fight against this global threat. The study aimed to explore the knowledge, perspectives and practices of physicians regarding various aspects of antibiotic stewardship program including antibiotic stewardship activities, rational use of antibiotics, antibiotic resistance, prescribing practices and factors associated with these practices. METHODS: In this qualitative study, a total of 17 semi-structured, in-depth interviews with doctors of three tertiary care public sector hospitals in Bahawalpur and Rahim Yar Khan were conducted. The convenient sampling method was adopted to collect the data and the saturation point criterion was applied to determine the sample size. Thematic analysis approach was used to draw conclusions from the data. RESULTS: The analysis of data yielded five themes, 12 subthemes and 26 categories. The themes included, (i) perception about antibiotic use and antibiotic stewardship, (ii) antibiotic prescription practices, (iii) antibiotic resistance, (iv) limited strategies adopted by hospital administration to ensure quality and safe distribution of antibiotics, (v) implementation of antibiotic stewardship program: barriers, suggestion and future benefits. Doctors had misconceptions about the rational use of antibiotics. The perception regarding antibiotic stewardship programs was poor. Moreover, very few activities related to ASP existed. The participants gave many suggestions for successful implementation of ASP in order to reduce the burden of antibiotic resistance, including development of guidelines for the use of antibiotics, strict legislation regarding use of antibiotics, active participation of healthcare professionals and awareness program among general public about the use of antibiotics. CONCLUSION: This study concluded that poor knowledge of doctors regarding ASP, non-existence of antibiogram of hospital and lack of rules for the safe use of antibiotics were the main driving factors associated with irrational antibiotic prescription practices and development of AR.


Asunto(s)
Programas de Optimización del Uso de los Antimicrobianos/métodos , Farmacorresistencia Microbiana , Conocimientos, Actitudes y Práctica en Salud , Percepción , Médicos/psicología , Antibacterianos/efectos adversos , Actitud del Personal de Salud , Prescripciones de Medicamentos , Femenino , Humanos , Masculino , Pakistán , Investigación Cualitativa
8.
Int J Mol Sci ; 22(6)2021 Mar 22.
Artículo en Inglés | MEDLINE | ID: mdl-33810172

RESUMEN

The relationship between autoimmunity and changes in intestinal microbiota is not yet fully understood. In this study, the role of intestinal microbiota in the onset and progression of autoimmune lesions in non-obese diabetic (NOD) mice was evaluated by administering antibiotics to alter their intestinal microenvironment. Flow cytometric analysis of spleen cells showed that antibiotic administration did not change the proportion or number of T and B cells in NOD mice, and pathological analysis demonstrated that autoimmune lesions in the salivary glands and in the pancreas were also not affected by antibiotic administration. These results suggest that the onset and progression of autoimmunity may be independent of enteral microbiota changes. Our findings may be useful for determining the appropriate use of antibiotics in patients with autoimmune diseases who are prescribed drugs to maintain systemic immune function.


Asunto(s)
Antibacterianos/farmacología , Enfermedades Autoinmunes/etiología , Autoinmunidad , Susceptibilidad a Enfermedades , Animales , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Enfermedades Autoinmunes/tratamiento farmacológico , Autoinmunidad/efectos de los fármacos , Citocinas/metabolismo , Modelos Animales de Enfermedad , Sistema Inmunológico/efectos de los fármacos , Sistema Inmunológico/inmunología , Sistema Inmunológico/metabolismo , Ratones , Ratones Endogámicos NOD , Sialadenitis/etiología , Sialadenitis/metabolismo , Sialadenitis/patología
9.
JAMA Netw Open ; 4(3): e212713, 2021 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-33755168

RESUMEN

Importance: Acute bacterial sinusitis is common, but currently recommended antibiotic treatment provides minimal benefit. Objective: To confirm the previous finding that high-dose amoxicillin plus clavulanate (with double the amount of amoxicillin) may be superior to standard-dose amoxicillin plus clavulanate in adults. Design, Setting, and Participants: This double-blind, comparative-effectiveness randomized clinical trial was conducted from February 26, 2018, through May 10, 2020, at the academic primary care internal medicine and pediatrics practice of Albany Medical Center, located in Cohoes, New York. Participants included adults aged 18 years or older who were prescribed amoxicillin plus clavulanate for acute bacterial sinusitis diagnosed in accordance with the Infectious Diseases Society of America guidelines. Interventions: Amoxicillin 875 mg with clavulanate 125 mg plus either placebo (standard dose) or amoxicillin 875 mg (high dose) twice a day for 7 days. Main Outcomes and Measures: The primary efficacy outcome was a global rating of "a lot better" or "no symptoms" at the end of 3 days of treatment using a Global Rating of Improvement scale, with outcomes ranging from 1 (a lot worse) to 6 (no symptoms). The primary adverse effect outcome was severe diarrhea at 3 or 10 days after the start of treatment. Results: At an unplanned interim analysis prompted by COVID-19 restrictions, 157 of a projected 240 participants had been enrolled (mean age, 48.5 [range, 18.7-84.0] years; 117 women [74.5%]), with 79 randomized to the standard dose and 78 to the high dose; 9 and 12, respectively, withdrew or were lost to follow-up before the assessment of the primary outcome. At day 3, 31 of 70 participants (44.3%) in the standard-dose group reported a global rating of "a lot better" or "no symptoms," as did 24 of 66 (36.4%) in the high-dose group, for a difference of -7.9% (95% CI, -24.4% to 8.5%; P = .35). The study was, therefore, stopped for futility. Diarrhea was common in both groups by day 3, with any diarrhea reported in 29 of 71 participants (40.8%) receiving the standard dose and 28 of 65 (43.1%) receiving the high dose and severe diarrhea reported in 5 of 71 (7.0%) and 5 of 65 (7.7%), respectively. Conclusions and Relevance: The results of this randomized clinical trial suggest that adults treated for clinically diagnosed acute sinusitis did not appear to benefit from taking high-dose compared with standard-dose amoxicillin plus clavulanate. Trial Registration: ClinicalTrials.gov Identifier: NCT03431337.


Asunto(s)
Amoxicilina , Ácido Clavulánico , Sinusitis , Enfermedad Aguda , Amoxicilina/administración & dosificación , Amoxicilina/efectos adversos , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Ácido Clavulánico/administración & dosificación , Ácido Clavulánico/efectos adversos , Diarrea/inducido químicamente , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Combinación de Medicamentos , Monitoreo de Drogas/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sinusitis/diagnóstico , Sinusitis/tratamiento farmacológico , Resultado del Tratamiento , Inhibidores de beta-Lactamasas/administración & dosificación , Inhibidores de beta-Lactamasas/efectos adversos
10.
Microb Drug Resist ; 27(3): 281-290, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33729874

RESUMEN

The coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2, has recently emerged worldwide. In this context, there is an urgent need to identify safe and effective therapeutic strategies for treatment of such highly contagious disease. We recently reported promising results of combining hydroxychloroquine and azithromycin as an early treatment option. Although ongoing clinical trials are challenging the efficacy of this combination, many clinicians claim the authorization to or have already begun to use it to treat COVID-19 patients worldwide. The aim of this article is to share pharmacology considerations contributing to the rationale of this combination, and to provide safety information to prevent toxicity and drug-drug interactions, based on available evidence.


Asunto(s)
Antibacterianos/uso terapéutico , Antivirales/uso terapéutico , Azitromicina/uso terapéutico , Hidroxicloroquina/uso terapéutico , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Antibacterianos/farmacología , Antivirales/administración & dosificación , Antivirales/efectos adversos , Antivirales/farmacología , Azitromicina/administración & dosificación , Azitromicina/efectos adversos , Azitromicina/farmacología , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Quimioterapia Combinada , Humanos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/efectos adversos , Hidroxicloroquina/farmacología
11.
Cochrane Database Syst Rev ; 3: CD008726, 2021 03 04.
Artículo en Inglés | MEDLINE | ID: mdl-33661539

RESUMEN

BACKGROUND: Caesarean section increases the risk of postpartum infection for women and prophylactic antibiotics have been shown to reduce the incidence; however, there are adverse effects. It is important to identify the most effective class of antibiotics to use and those with the least adverse effects.  OBJECTIVES: To determine, from the best available evidence, the balance of benefits and harms between different classes of antibiotic given prophylactically to women undergoing caesarean section, considering their effectiveness in reducing infectious complications for women and adverse effects on both mother and infant. SEARCH METHODS: For this 2020 update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (2 December 2019), and reference lists of retrieved studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs) comparing different classes of prophylactic antibiotics given to women undergoing caesarean section.  RCTs published in abstract form were also included. We excluded trials that compared drugs with placebo or drugs within a specific class; these are assessed in other Cochrane Reviews. We excluded quasi-RCTs and cross-over trials. Cluster-RCTs were eligible for inclusion but none were identified. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. We assessed the certainty of the evidence using the GRADE approach. MAIN RESULTS: We included 39 studies, with 33 providing data (8073 women). Thirty-two studies (7690 women) contributing data administered antibiotics systemically, while one study (383 women) used lavage and was analysed separately. We identified three main comparisons that addressed clinically important questions on antibiotics at caesarean section (all systemic administration), but we only found studies for one comparison, 'antistaphylococcal cephalosporins (1st and 2nd generation) versus broad spectrum penicillins plus betalactamase inhibitors'.   We found no studies for the following comparisons: 'antistaphylococcal cephalosporins (1st and 2nd generation) versus lincosamides' and 'antistaphylococcal cephalosporins (1st and 2nd generation) versus lincosamides plus aminoglycosides'. Twenty-seven studies (22 provided data) included comparisons of cephalosporins (only) versus penicillins (only). However for this update, we only pooled data relating to different sub-classes of penicillins and cephalosporins where they are known to have similar spectra of action against agents likely to cause infection at caesarean section. Eight trials, providing data on 1540 women, reported on our main comparison, 'antistaphylococcal cephalosporins (1st and 2nd generation) versus broad spectrum penicillins plus betalactamase inhibitors'. We found data on four other comparisons of cephalosporins (only) versus penicillins (only) using systemic administration: antistaphylococcal cephalosporins (1st and 2nd generation) versus non-antistaphylococcal penicillins (natural and broad spectrum) (9 studies, 3093 women); minimally antistaphylococcal cephalosporins (3rd generation) versus non-antistaphylococcal penicillins (natural and broad spectrum) (4 studies, 854 women); minimally antistaphylococcal cephalosporins (3rd generation) versus broad spectrum penicillins plus betalactamase inhibitors (2 studies, 865 women); and minimally antistaphylococcal cephalosporins (3rd generation) versus broad spectrum and antistaphylococcal penicillins (1 study, 200 women). For other comparisons of different classes of antibiotics, only a small number of trials provided data for each comparison, and in all but one case data were not pooled. For all comparisons, there was a lack of good quality data and important outcomes often included few women. Three of the studies that contributed data were undertaken with drug company funding, one was funded by the hospital, and for all other studies the funding source was not reported. Most of the studies were at unclear risk of selection bias, reporting bias and other biases, partly due to the inclusion of many older trials where trial reports did not provide sufficient methodological information. We undertook GRADE assessment on the only main comparison reported by the included studies, antistaphylococcal cephalosporins (1st and 2nd generation) versus broad spectrum penicillins plus betalactamase inhibitors, and the certainty ranged from low to very low, mostly due to concerns about risk of bias, wide confidence intervals (CI), and few events. In terms of the primary outcomes for our main comparison of 'antistaphylococcal cephalosporins (1st and 2nd generation) versus broad spectrum penicillins plus betalactamase inhibitors': only one small study reported sepsis, and there were too few events to identify clear differences between the drugs (risk ratio (RR) 2.37, 95% CI 0.10 to 56.41, 1 study, 75 women, very low-certainty evidence). There may be little or no difference between these antibiotics in preventing endometritis (RR 1.10; 95% CI 0.76 to 1.60, 7 studies, 1161 women; low-certainty evidence). None of the included studies reported on infant sepsis or infant oral thrush. For our secondary outcomes, we found there may be little or no difference between interventions for maternal fever (RR 1.07, 95% CI 0.65 to 1.75, 3 studies, 678 women; low-certainty evidence). We are uncertain of the effects on maternal: wound infection (RR 0.78, 95% CI 0.32 to 1.90, 4 studies, 543 women), urinary tract infection (average RR 0.64, 95% CI 0.11 to 3.73, 4 studies, 496 women), composite adverse effects (RR 0.96, 95% CI 0.09 to 10.50, 2 studies, 468 women), and skin rash (RR 1.08, 95% CI 0.28 to 4.1, 3 studies, 591 women) (all very low certainty evidence). Although maternal allergic reactions were reported by two studies, there were no events. There were no infant outcomes reported in the included studies. For the other comparisons, the results for most outcomes had wide CIs, few studies and few women included. None of the included trials reported on longer-term maternal outcomes, or on any infant outcomes. AUTHORS' CONCLUSIONS: Based on the best currently available evidence, 'antistaphylococcal cephalosporins' and 'broad spectrum penicillins plus betalactamase inhibitors' may have similar efficacy at caesarean section when considering immediate postoperative infection, although we did not have clear evidence for several important outcomes. Most trials administered antibiotics at or after cord clamping, or post-operatively, so results may have limited applicability to current practice which generally favours administration prior to skin incision. We have no data on any infant outcomes, nor on late infections (up to 30 days) in the mother; these are important gaps in the evidence that warrant further research. Antimicrobial resistance is very important but more appropriately investigated by other trial designs.


Asunto(s)
Antibacterianos/uso terapéutico , Infecciones Bacterianas/prevención & control , Cefalosporinas/uso terapéutico , Cesárea/efectos adversos , Penicilinas/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Antibacterianos/efectos adversos , Antibacterianos/clasificación , Profilaxis Antibiótica/métodos , Cefalosporinas/efectos adversos , Femenino , Humanos , Recién Nacido , Penicilinas/efectos adversos , Embarazo , Infección Puerperal/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto , Inhibidores de beta-Lactamasas/uso terapéutico
12.
Medicine (Baltimore) ; 100(8): e24883, 2021 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-33663117

RESUMEN

BACKGROUND: Meropenem monotherapy vs ceftazidime plus amikacin have been approved for use against febrile neutropenia. To assess the effectiveness and safety of them for empirical treatment of cancer patients with febrile neutropenia, we conducted a meta-analysis of randomized controlled trial. METHODS: Randomized controlled trials on ceftazidime plus amikacin, or/and monotherapy with meropenem for the treatment of cancer patients with febrile neutropenia were identified by searching Cochrane Library, PubMed, Science Direct, Wiley Online, Science Citation Index, Google (scholar), National Center for Biotechnology Information, and China National Knowledge Infrastructure. Data on interventions, participants' characteristics and the outcomes of therapy, were extracted for statistical analysis. Seven trials fulfilled the inclusion criteria. RESULT: The treatment with ceftazidime plus amikacin was more effective than meropenem (OR = 1.17; 95% CI 0.93-1.46; 1270 participants). However, the treatment effects of the 2 therapy methods were almost parallel in adults (OR = 1.15; 95% CI 0.91-1.46; 1130 participants older than 16). Drug-related adverse effects afflicted more patients treated with ceftazidime plus amikacin (OR = 0.78; 95% CI 0.52-1.15; 1445 participants). The common responses were nausea, diarrhea, rash, and increased in serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase and bilirubin. CONCLUSION: Ceftazidime plus amikacin should be the first choice for empirical treatment of cancer patients with febrile neutropenia, and meropenem may be chosen as a last defense against pathogenic bacteria.


Asunto(s)
Amicacina/administración & dosificación , Antibacterianos/administración & dosificación , Ceftazidima/administración & dosificación , Neutropenia Febril/tratamiento farmacológico , Meropenem/administración & dosificación , Amicacina/efectos adversos , Antibacterianos/efectos adversos , Ceftazidima/efectos adversos , Quimioterapia Combinada , Humanos , Meropenem/efectos adversos , Neoplasias/tratamiento farmacológico
16.
Cochrane Database Syst Rev ; 2: CD003610, 2021 02 23.
Artículo en Inglés | MEDLINE | ID: mdl-33704780

RESUMEN

BACKGROUND: Coronary heart disease is the leading cause of mortality worldwide with approximately 7.4 million deaths each year. People with established coronary heart disease have a high risk of subsequent cardiovascular events including myocardial infarction, stroke, and cardiovascular death. Antibiotics might prevent such outcomes due to their antibacterial, antiinflammatory, and antioxidative effects. However, a randomised clinical trial and several observational studies have suggested that antibiotics may increase the risk of cardiovascular events and mortality. Furthermore, several non-Cochrane Reviews, that are now outdated, have assessed the effects of antibiotics for coronary heart disease and have shown conflicting results. No previous systematic review using Cochrane methodology has assessed the effects of antibiotics for coronary heart disease. OBJECTIVES: We assessed the benefits and harms of antibiotics compared with placebo or no intervention for the secondary prevention of coronary heart disease. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, LILACS, SCI-EXPANDED, and BIOSIS in December 2019 in order to identify relevant trials. Additionally, we searched TRIP, Google Scholar, and nine trial registries in December 2019. We also contacted 11 pharmaceutical companies and searched the reference lists of included trials, previous systematic reviews, and other types of reviews. SELECTION CRITERIA: Randomised clinical trials assessing the effects of antibiotics versus placebo or no intervention for secondary prevention of coronary heart disease in adult participants (≥18 years). Trials were included irrespective of setting, blinding, publication status, publication year, language, and reporting of our outcomes. DATA COLLECTION AND ANALYSIS: Three review authors independently extracted data. Our primary outcomes were all-cause mortality, serious adverse event according to the International Conference on Harmonization - Good Clinical Practice (ICH-GCP), and quality of life. Our secondary outcomes were cardiovascular mortality, myocardial infarction, stroke, and sudden cardiac death. Our primary time point of interest was at maximum follow-up. Additionally, we extracted outcome data at 24±6 months follow-up. We assessed the risks of systematic errors using Cochrane 'Rosk of bias' tool. We calculated risk ratios (RRs) with 95% confidence intervals (CIs) for dichotomous outcomes. We calculated absolute risk reduction (ARR) or increase (ARI) and number needed to treat for an additional beneficial outcome (NNTB) or for an additional harmful outcome (NNTH) if the outcome result showed a beneficial or harmful effect, respectively. The certainty of the body of evidence was assessed by GRADE. MAIN RESULTS: We included 38 trials randomising a total of 26,638 participants (mean age 61.6 years), with 23/38 trials reporting data on 26,078 participants that could be meta-analysed. Three trials were at low risk of bias and the 35 remaining trials were at high risk of bias. Trials assessing the effects of macrolides (28 trials; 22,059 participants) and quinolones (two trials; 4162 participants) contributed with the vast majority of the data. Meta-analyses at maximum follow-up showed that antibiotics versus placebo or no intervention seemed to increase the risk of all-cause mortality (RR 1.06; 95% CI 0.99 to 1.13; P = 0.07; I2 = 0%; ARI 0.48%; NNTH 208; 25,774 participants; 20 trials; high certainty of evidence), stroke (RR 1.14; 95% CI 1.00 to 1.29; P = 0.04; I2 = 0%; ARI 0.73%; NNTH 138; 14,774 participants; 9 trials; high certainty of evidence), and probably also cardiovascular mortality (RR 1.11; 95% CI 0.98 to 1.25; P = 0.11; I2= 0%; 4674 participants; 2 trials; moderate certainty of evidence). Little to no difference was observed when assessing the risk of myocardial infarction (RR 0.95; 95% CI 0.88 to 1.03; P = 0.23; I2 = 0%; 25,523 participants; 17 trials; high certainty of evidence). No evidence of a difference was observed when assessing sudden cardiac death (RR 1.08; 95% CI 0.90 to 1.31; P = 0.41; I2 = 0%; 4520 participants; 2 trials; moderate certainty of evidence). Meta-analyses at 24±6 months follow-up showed that antibiotics versus placebo or no intervention increased the risk of all-cause mortality (RR 1.25; 95% CI 1.06 to 1.48; P = 0.007; I2 = 0%; ARI 1.26%; NNTH 79 (95% CI 335 to 42); 9517 participants; 6 trials; high certainty of evidence), cardiovascular mortality (RR 1.50; 95% CI 1.17 to 1.91; P = 0.001; I2 = 0%; ARI 1.12%; NNTH 89 (95% CI 261 to 49); 9044 participants; 5 trials; high certainty of evidence), and probably also sudden cardiac death (RR 1.77; 95% CI 1.28 to 2.44; P = 0.0005; I2 = 0%; ARI 1.9%; NNTH 53 (95% CI 145 to 28); 4520 participants; 2 trials; moderate certainty of evidence). No evidence of a difference was observed when assessing the risk of myocardial infarction (RR 0.95; 95% CI 0.82 to 1.11; P = 0.53; I2 = 43%; 9457 participants; 5 trials; moderate certainty of evidence) and stroke (RR 1.17; 95% CI 0.90 to 1.52; P = 0.24; I2 = 0%; 9457 participants; 5 trials; high certainty of evidence). Meta-analyses of trials at low risk of bias differed from the overall analyses when assessing cardiovascular mortality at maximum follow-up. For all other outcomes, meta-analyses of trials at low risk of bias did not differ from the overall analyses. None of the trials specifically assessed serious adverse event according to ICH-GCP. No data were found on quality of life. AUTHORS' CONCLUSIONS: Our present review indicates that antibiotics (macrolides or quinolones) for secondary prevention of coronary heart disease seem harmful when assessing the risk of all-cause mortality, cardiovascular mortality, and stroke at maximum follow-up and all-cause mortality, cardiovascular mortality, and sudden cardiac death at 24±6 months follow-up. Current evidence does, therefore, not support the clinical use of macrolides and quinolones for the secondary prevention of coronary heart disease. Future trials on the safety of macrolides or quinolones for the secondary prevention in patients with coronary heart disease do not seem ethical. In general, randomised clinical trials assessing the effects of antibiotics, especially macrolides and quinolones, need longer follow-up so that late-occurring adverse events can also be assessed.


Asunto(s)
Antibacterianos/efectos adversos , Enfermedad Coronaria/prevención & control , Prevención Secundaria/métodos , Antibacterianos/uso terapéutico , Enfermedades Cardiovasculares/mortalidad , Causas de Muerte , Enfermedad Coronaria/mortalidad , Muerte Súbita Cardíaca/epidemiología , Humanos , Macrólidos/efectos adversos , Macrólidos/uso terapéutico , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Quinolonas/efectos adversos , Quinolonas/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Accidente Cerebrovascular/epidemiología
17.
Cochrane Database Syst Rev ; 3: CD004406, 2021 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-33728634

RESUMEN

BACKGROUND: Antibiotics provide only modest benefit in treating sore throat, although their effectiveness increases in people with positive throat swabs for group A beta-haemolytic streptococci (GABHS). It is unclear which antibiotic is the best choice if antibiotics are indicated. This is an update of a review first published in 2010, and updated in 2013, 2016, and 2020. OBJECTIVES: To assess the comparative efficacy of different antibiotics in: (a) alleviating symptoms (pain, fever); (b) shortening the duration of the illness; (c) preventing clinical relapse (i.e. recurrence of symptoms after initial resolution); and (d) preventing complications (suppurative complications, acute rheumatic fever, post-streptococcal glomerulonephritis). To assess the evidence on the comparative incidence of adverse effects and the risk-benefit of antibiotic treatment for streptococcal pharyngitis. SEARCH METHODS: We searched the following databases up to 3 September 2020: CENTRAL (2020, Issue 8), MEDLINE Ovid (from 1946), Embase Elsevier (from 1974), and Web of Science Thomson Reuters (from 2010). We also searched clinical trial registers on 3 September 2020. SELECTION CRITERIA: Randomised, double-blind trials comparing different antibiotics, and reporting at least one of the following: clinical cure, clinical relapse, or complications and/or adverse events. DATA COLLECTION AND ANALYSIS: Two review authors independently screened trials for inclusion and extracted data using standard methodological procedures as recommended by Cochrane. We assessed the risk of bias of included studies according to the methods outlined in the Cochrane Handbook for Systematic Reviews of Interventions, and used the GRADE approach to assess the overall certainty of the evidence for the outcomes. We have reported the intention-to-treat analysis, and also performed an analysis of evaluable participants to explore the robustness of the intention-to-treat results. MAIN RESULTS: We included 19 trials reported in 18 publications (5839 randomised participants): six trials compared penicillin with cephalosporins; six compared penicillin with macrolides; three compared penicillin with carbacephem; one compared penicillin with sulphonamides; one compared clindamycin with ampicillin; and one compared azithromycin with amoxicillin in children. All participants had confirmed acute GABHS tonsillopharyngitis, and ages ranged from one month to 80 years. Nine trials included only, or predominantly, children. Most trials were conducted in an outpatient setting. Reporting of randomisation, allocation concealment, and blinding was poor in all trials. We downgraded the certainty of the evidence mainly due to lack of (or poor reporting of) randomisation or blinding, or both; heterogeneity; and wide confidence intervals. Cephalosporins versus penicillin We are uncertain if there is a difference in symptom resolution (at 2 to 15 days) for cephalosporins versus penicillin (odds ratio (OR) for absence of symptom resolution 0.79, 95% confidence interval (CI) 0.55 to 1.12; 5 trials; 2018 participants; low-certainty evidence). Results of the sensitivity analysis of evaluable participants differed (OR 0.51, 95% CI 0.27 to 0.97; 5 trials; 1660 participants; very low-certainty evidence). We are uncertain if clinical relapse may be lower for cephalosporins compared with penicillin (OR 0.55, 95% CI 0.30 to 0.99; number needed to treat for an additional beneficial outcome (NNTB) 50; 4 trials; 1386 participants; low-certainty evidence). Very low-certainty evidence showed no difference in reported adverse events. Macrolides versus penicillin We are uncertain if there is a difference between macrolides and penicillin for resolution of symptoms (OR 1.11, 95% CI 0.92 to 1.35; 6 trials; 1728 participants; low-certainty evidence). Sensitivity analysis of evaluable participants resulted in an OR of 0.79, 95% CI 0.57 to 1.09; 6 trials; 1159 participants). We are uncertain if clinical relapse may be different (OR 1.21, 95% CI 0.48 to 3.03; 6 trials; 802 participants; low-certainty evidence).  Azithromycin versus amoxicillin Based on one unpublished trial in children, we are uncertain if resolution of symptoms is better with azithromycin in a single dose versus amoxicillin for 10 days (OR 0.76, 95% CI 0.55 to 1.05; 1 trial; 673 participants; very low-certainty evidence). Sensitivity analysis for per-protocol analysis resulted in an OR of 0.29, 95% CI 0.11 to 0.73; 1 trial; 482 participants; very low-certainty evidence). We are also uncertain if there was a difference in relapse between groups (OR 0.88, 95% CI 0.43 to 1.82; 1 trial; 422 participants; very low-certainty evidence). Adverse events were more common with azithromycin compared to amoxicillin (OR 2.67, 95% CI 1.78 to 3.99; 1 trial; 673 participants; very low-certainty evidence). Carbacephem versus penicillin There is low-certainty evidence that compared with penicillin, carbacephem may provide better symptom resolution post-treatment in adults and children (OR 0.70, 95% CI 0.49 to 0.99; NNTB 14.3; 3 trials; 795 participants). Studies did not report on long-term complications, so it was unclear if any class of antibiotics was better in preventing serious but rare complications.  AUTHORS' CONCLUSIONS: We are uncertain if there are clinically relevant differences in symptom resolution when comparing cephalosporins and macrolides with penicillin in the treatment of GABHS tonsillopharyngitis. Low-certainty evidence in children suggests that carbacephem may be more effective than penicillin for symptom resolution. There is insufficient evidence to draw conclusions regarding the other comparisons in this review. Data on complications were too scarce to draw conclusions. These results do not demonstrate that other antibiotics are more effective than penicillin in the treatment of GABHS pharyngitis. All studies were conducted in high-income countries with a low risk of streptococcal complications, so there is a need for trials in low-income countries and Aboriginal communities, where the risk of complications remains high.


Asunto(s)
Antibacterianos/uso terapéutico , Faringitis/tratamiento farmacológico , Infecciones Estreptocócicas/tratamiento farmacológico , Streptococcus pyogenes , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Amoxicilina/efectos adversos , Amoxicilina/uso terapéutico , Ampicilina/efectos adversos , Ampicilina/uso terapéutico , Antibacterianos/efectos adversos , Azitromicina/efectos adversos , Azitromicina/uso terapéutico , Cefalosporinas/efectos adversos , Cefalosporinas/uso terapéutico , Niño , Preescolar , Clindamicina/efectos adversos , Clindamicina/uso terapéutico , Humanos , Lactante , Macrólidos/efectos adversos , Macrólidos/uso terapéutico , Persona de Mediana Edad , Penicilinas/efectos adversos , Penicilinas/uso terapéutico , Faringitis/microbiología , Ensayos Clínicos Controlados Aleatorios como Asunto , Infecciones Estreptocócicas/microbiología , Sulfonamidas/efectos adversos , Sulfonamidas/uso terapéutico , Adulto Joven
18.
Cochrane Database Syst Rev ; 2: CD003811, 2021 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-33624847

RESUMEN

BACKGROUND: The most frequent indications for tooth extractions, generally performed by general dental practitioners, are dental caries and periodontal infections. Systemic antibiotics may be prescribed to patients undergoing extractions to prevent complications due to infection. This is an update of a review first published in 2012. OBJECTIVES: To determine the effect of systemic antibiotic prophylaxis on the prevention of infectious complications following tooth extractions. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health Trials Register (to 16 April 2020), the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library, 2020, Issue 3), MEDLINE Ovid (1946 to 16 April 2020), Embase Ovid (1980 to 16 April 2020), and LILACS (1982 to 16 April 2020). The US National Institutes of Health Trials Registry (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: We included randomised, double-blind, placebo-controlled trials of systemic antibiotic prophylaxis in patients undergoing tooth extraction(s) for any indication. DATA COLLECTION AND ANALYSIS: At least two review authors independently performed data extraction and 'Risk of bias' assessment for the included studies. We contacted trial authors for further details where these were unclear. For dichotomous outcomes, we calculated risk ratios (RR) and 95% confidence intervals (CI) using random-effects models. For continuous outcomes, we used mean differences (MD) with 95% CI using random-effects models. We examined potential sources of heterogeneity. We assessed the certainty of the body of evidence for key outcomes as high, moderate, low, or very low, using the GRADE approach. MAIN RESULTS: We included 23 trials that randomised approximately 3206 participants (2583 analysed) to prophylactic antibiotics or placebo. Although general dentists perform dental extractions because of severe dental caries or periodontal infection, only one of the trials evaluated the role of antibiotic prophylaxis in groups of patients affected by those clinical conditions. We assessed 16 trials as being at high risk of bias, three at low risk, and four as unclear.  Compared to placebo, antibiotics may reduce the risk of postsurgical infectious complications in patients undergoing third molar extractions by approximately 66% (RR 0.34, 95% CI 0.19 to 0.64; 1728 participants; 12 studies; low-certainty evidence), which means that 19 people (95% CI 15 to 34) need to be treated with antibiotics to prevent one infection following extraction of impacted wisdom teeth. Antibiotics may also reduce the risk of dry socket by 34% (RR 0.66, 95% CI 0.45 to 0.97; 1882 participants; 13 studies; low-certainty evidence), which means that 46 people (95% CI 29 to 62) need to take antibiotics to prevent one case of dry socket following extraction of impacted wisdom teeth. The evidence for our other outcomes is uncertain: pain, whether measured dichotomously as presence or absence (RR 0.59, 95% CI 0.31 to 1.12; 675 participants; 3 studies) or continuously using a visual analogue scale (0-to-10-centimetre scale, where 0 is no pain) (MD -0.26, 95% CI -0.59 to 0.07; 422 participants; 4 studies); fever (RR 0.66, 95% CI 0.24 to 1.79; 475 participants; 4 studies); and adverse effects, which were mild and transient (RR 1.46, 95% CI 0.81 to 2.64; 1277 participants; 8 studies) (very low-certainty evidence).  We found no clear evidence that the timing of antibiotic administration (preoperative, postoperative, or both) was important. The included studies enrolled a subset of patients undergoing dental extractions, that is healthy people who had surgical extraction of third molars. Consequently, the results of this review may not be generalisable to all people undergoing tooth extractions. AUTHORS' CONCLUSIONS: The vast majority (21 out of 23) of the trials included in this review included only healthy patients undergoing extraction of impacted third molars, often performed by oral surgeons. None of the studies evaluated tooth extraction in immunocompromised patients. We found low-certainty evidence that prophylactic antibiotics may reduce the risk of infection and dry socket following third molar extraction when compared to placebo, and very low-certainty evidence of no increase in the risk of adverse effects. On average, treating 19 healthy patients with prophylactic antibiotics may stop one person from getting an infection. It is unclear whether the evidence in this review is generalisable to patients with concomitant illnesses or patients at a higher risk of infection. Due to the increasing prevalence of bacteria that are resistant to antibiotic treatment, clinicians should evaluate if and when to prescribe prophylactic antibiotic therapy before a dental extraction for each patient on the basis of the patient's clinical conditions (healthy or affected by systemic pathology) and level of risk from infective complications. Immunocompromised patients, in particular, need an individualised approach in consultation with their treating medical specialist.


Asunto(s)
Antibacterianos/uso terapéutico , Profilaxis Antibiótica , Tercer Molar/cirugía , Complicaciones Posoperatorias/prevención & control , Extracción Dental/efectos adversos , Diente Impactado/cirugía , Antibacterianos/efectos adversos , Profilaxis Antibiótica/efectos adversos , Infecciones Bacterianas/prevención & control , Sesgo , Ensayos Clínicos Controlados como Asunto , Alveolo Seco/prevención & control , Humanos , Dolor Postoperatorio/prevención & control
20.
Microbiome ; 9(1): 39, 2021 02 06.
Artículo en Inglés | MEDLINE | ID: mdl-33549144

RESUMEN

BACKGROUND: The gut microbiota plays a central role in host physiology and in several pathological mechanisms in humans. Antibiotics compromise the composition and functions of the gut microbiota inducing long-lasting detrimental effects on the host. Recent studies suggest that the efficacy of different clinical therapies depends on the action of the gut microbiota. Here, we investigated how different antibiotic treatments affect the ability of the gut microbiota to control intestinal inflammation upon fecal microbiota transplantation in an experimental colitis model and in ex vivo experiments with human intestinal biopsies. RESULTS: Murine fecal donors were pre-treated with different antibiotics, i.e., vancomycin, streptomycin, and metronidazole before FMT administration to colitic animals. The analysis of the gut microbiome, fecal metabolome, and the immunophenotyping of colonic lamina propria immune cells revealed that antibiotic pre-treatment significantly influences the capability of the microbiota to control intestinal inflammation. Streptomycin and vancomycin-treated microbiota failed to control intestinal inflammation and were characterized by the blooming of pathobionts previously associated with IBD as well as with metabolites related to the presence of oxidative stress and metabolism of simple sugars. On the contrary, the metronidazole-treated microbiota retained its ability to control inflammation co-occurring with the enrichment of Lactobacillus and of innate immune responses involving iNKT cells. Furthermore, ex vivo cultures of human intestinal lamina propria mononuclear cells and iNKT cell clones from IBD patients with vancomycin pre-treated sterile fecal water showed a Th1/Th17 skewing in CD4+ T-cell populations; metronidazole, on the other hand, induced the polarization of iNKT cells toward the production of IL10. CONCLUSIONS: Diverse antibiotic regimens affect the ability of the gut microbiota to control intestinal inflammation in experimental colitis by altering the microbial community structure and microbiota-derived metabolites. Video Abstract.


Asunto(s)
Antibacterianos/efectos adversos , Colitis/inducido químicamente , Colitis/microbiología , Modelos Animales de Enfermedad , Disbiosis/microbiología , Trasplante de Microbiota Fecal , Microbioma Gastrointestinal/efectos de los fármacos , Animales , Antibacterianos/farmacología , Colitis/inmunología , Colitis/patología , Disbiosis/inducido químicamente , Femenino , Microbioma Gastrointestinal/inmunología , Humanos , Masculino , Metronidazol/farmacología , Ratones , Células T Asesinas Naturales/efectos de los fármacos , Células T Asesinas Naturales/inmunología , Estreptomicina/efectos adversos , Células TH1/efectos de los fármacos , Células TH1/inmunología , Células Th17/efectos de los fármacos , Células Th17/inmunología , Vancomicina/efectos adversos
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