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1.
Waste Manag ; 105: 248-255, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32088571

RESUMO

Penicillin V mycelial residue (PMR) is a byproduct of the pharmaceutical industry and may be disposed through land application after alkaline-thermal treatment. However, the efficacy of alkaline-thermally treated PMR in soil amelioration and the potential contamination risk caused by introduced penicillin V are poorly understood. In this study, soil pH, the contents of organic matter, available phosphorus, available potassium were measured to study the effect of alkaline-thermally treated PMR on soil fertility; the numbers of culturable microorganisms and the activities of enzymes, which not only reflect the decomposing ability of organic matter but also monitor the ecological suppression in soil ecosystem, were also investigated; moreover, the persistence of introduced penicillin V and the variation of antibiotic resistance genes (ARGs) in soil were examined to evaluate the resulting antibiotic resistance risk. The results indicated that the pH and the content of available potassium in amended soil with treated PMR profoundly improved. In addition, the culturable microorganisms and enzymes were not inhibited throughout the incubation of treated PMR in soil. The stability of treated PMR in soil relatively completed after 43 days. More importantly, the penicillin V derived by treated PMR rapidly depleted within 3 days, which suggested a relatively low environmental persistence. The treated PMR did not enrich the ARGs detected in soil, demonstrating that the addition of treated PMR might not trigger the antibiotic resistance risk in the short-term in soil. In conclusion, our results concluded that alkaline-thermally treated PMR is available for soil application.


Assuntos
Poluentes do Solo , Solo , Antibacterianos , Resistência Microbiana a Medicamentos , Ecossistema , Genes Bacterianos , Penicilina V , Microbiologia do Solo
3.
BMJ ; 367: l5337, 2019 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-31585944

RESUMO

OBJECTIVE: To determine whether total exposure to penicillin V can be reduced while maintaining adequate clinical efficacy when treating pharyngotonsillitis caused by group A streptococci. DESIGN: Open label, randomised controlled non-inferiority study. SETTING: 17 primary healthcare centres in Sweden between September 2015 and February 2018. PARTICIPANTS: Patients aged 6 years and over with pharyngotonsillitis caused by group A streptococci and three or four Centor criteria (fever ≥38.5°C, tender lymph nodes, coatings of the tonsils, and absence of cough). INTERVENTIONS: Penicillin V 800 mg four times daily for five days (total 16 g) compared with the current recommended dose of 1000 mg three times daily for 10 days (total 30 g). MAIN OUTCOME MEASURES: Primary outcome was clinical cure five to seven days after the end of antibiotic treatment. The non-inferiority margin was prespecified to 10 percentage points. Secondary outcomes were bacteriological eradication, time to relief of symptoms, frequency of relapses, complications and new tonsillitis, and patterns of adverse events. RESULTS: Patients (n=433) were randomly allocated to the five day (n=215) or 10 day (n=218) regimen. Clinical cure in the per protocol population was 89.6% (n=181/202) in the five day group and 93.3% (n=182/195) in the 10 day group (95% confidence interval -9.7 to 2.2). Bacteriological eradication was 80.4% (n=156/194) in the five day group and 90.7% (n=165/182) in the 10 day group. Eight and seven patients had relapses, no patients and four patients had complications, and six and 13 patients had new tonsillitis in the five day and 10 day groups, respectively. Time to relief of symptoms was shorter in the five day group. Adverse events were mainly diarrhoea, nausea, and vulvovaginal disorders; the 10 day group had higher incidence and longer duration of adverse events. CONCLUSIONS: Penicillin V four times daily for five days was non-inferior in clinical outcome to penicillin V three times daily for 10 days in patients with pharyngotonsillitis caused by group A streptococci. The number of relapses and complications did not differ between the two intervention groups. Five day treatment with penicillin V four times daily might be an alternative to the currently recommended 10 day regimen. TRIAL REGISTRATION: EudraCT 2015-001752-30; ClinicalTrials.gov NCT02712307.


Assuntos
Antibacterianos/administração & dosagem , Penicilina V/administração & dosagem , Faringite/tratamento farmacológico , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus pyogenes/efeitos dos fármacos , Tonsilite/tratamento farmacológico , Adolescente , Adulto , Idoso , Antibacterianos/efeitos adversos , Criança , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Penicilina V/efeitos adversos , Atenção Primária à Saúde , Resultado do Tratamento , Adulto Jovem
4.
Thromb Haemost ; 19(10): 1617-1623, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31352678

RESUMO

BACKGROUND: Data indicate that codispensing flucloxacillin to patients already on warfarin may result in decreased warfarin efficacy. OBJECTIVES: This article investigates the effect of flucloxacillin on warfarin anticoagulation. PATIENTS AND METHODS: In a retrospective cohort study of warfarin users, using three nationwide registers we included 5,848 patients receiving 10 days flucloxacillin treatment and 201 with ≥30 days treatment. To assess the potential for confounding by indication, we also identified 21,430 individuals initiating phenoxymethylpenicillin. International normalized ratio (INR) values and warfarin doses were calculated day-by-day and proportion of patients with a subtherapeutic INR week-by-week during cotreatment. RESULTS: Following initiation of flucloxacillin with a planned treatment duration of 10 days and ≥30 days, the mean INR decreased from 2.36 (95% confidence interval [CI] 2.34; 2.37) to 2.20 (95% CI 2.19; 2.21) and from 2.24 (95% CI 2.16; 2.32) to 1.96 (95% CI 1.89; 2.02), respectively. Consequently, for individuals with 10 days treatment the proportion of patients with a subtherapeutic INR of < 2 increased from 22% in the week preceding flucloxacillin initiation to 35% in the third week after initiation of flucloxacillin. In patients with 30 days treatment, the proportion increased from 34 to 63% by week 6. In individuals initiating phenoxymethylpenicillin, INR levels did not decrease. CONCLUSION: One in three patients with 10 days flucloxacillin and almost two in three patients initiating long-term treatment, was exposed to a subsequent subtherapeutic anticoagulant effect. To avoid unnecessary thromboembolic complications, the initiation of flucloxacillin should be accompanied by closer INR monitoring which may be especially important among individuals with lengthy treatments.


Assuntos
Anticoagulantes/administração & dosagem , Floxacilina/administração & dosagem , Tromboembolia/tratamento farmacológico , Varfarina/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Coagulação Sanguínea/efeitos dos fármacos , Estudos de Coortes , Feminino , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Penicilina V/administração & dosagem , Sistema de Registros , Estudos Retrospectivos , Suécia/epidemiologia
5.
Artigo em Inglês | MEDLINE | ID: mdl-31248086

RESUMO

(1) Background: Antibiotics are frequently used on farm animals, making animal husbandry a relatively large source of antibiotic pollution of the environment. The present study aims to isolate and acclimatize antibiotic-degrading bacterial strains for penicillin V potassium (PVK) from the contaminated soil of a pig farm. (2) Methods: Bacterial strains were isolated and acclimatized by continuous enrichment of cultures with PVK as the sole carbon source. The antibiotic susceptibility test, thiol mercury salt ultraviolet spectrophotometry (TMSUS), morphological observations, and 16S rDNA sequence analysis were used to identify and characterize the isolated strains. (3) Results: Four bacterial isolates (denoted as LM-1, LM-2, LM-3, LM-4) were obtained, and two of them (LM-1, LM-2) with the highest degradation rates were identified to belong to the same genera as Bacillus. These two isolates were found to be resistant to PVK antibiotic in an antibiotic sensitivity test. The TMSUS indicated that the strains LM-1 and LM-2 had good performance in PVK degradation (68% for LM-1, 66% for LM-2 in 48 h) when the initial PVK concentration was about 100 µg/mL. (4) Conclusions: Two bacterial strains isolated from the soil on a pig farm are effective in degrading PVK and can be potentially used for bioremediation of PVK antibiotic-contaminated soils.


Assuntos
Antibacterianos/metabolismo , Bactérias/isolamento & purificação , Bactérias/metabolismo , Biodegradação Ambiental , Fazendas , Penicilina V/metabolismo , Animais , China , Microbiologia do Solo , Suínos
6.
ACS Sens ; 4(4): 1072-1080, 2019 04 26.
Artigo em Inglês | MEDLINE | ID: mdl-30950598

RESUMO

Antimicrobial resistance poses a global threat to patient health. Improving the use and effectiveness of antimicrobials is critical in addressing this issue. This includes optimizing the dose of antibiotic delivered to each individual. New sensing approaches that track antimicrobial concentration for each patient in real time could allow individualized drug dosing. This work presents a potentiometric microneedle-based biosensor to detect levels of ß-lactam antibiotics in vivo in a healthy human volunteer. The biosensor is coated with a pH-sensitive iridium oxide layer, which detects changes in local pH as a result of ß-lactam hydrolysis by ß-lactamase immobilized on the electrode surface. Development and optimization of the biosensor coatings are presented, giving a limit of detection of 6.8 µM in 10 mM PBS solution. Biosensors were found to be stable for up to 2 weeks at -20 °C and to withstand sterilization. Sensitivity was retained after application for 6 h in vivo. Proof-of-concept results are presented showing that penicillin concentrations measured using the microneedle-based biosensor track those measured using both discrete blood and microdialysis sampling in vivo. These preliminary results show the potential of this microneedle-based biosensor to provide a minimally invasive means to measure real-time ß-lactam concentrations in vivo, representing an important first step toward a closed-loop therapeutic drug monitoring system.


Assuntos
Antibacterianos/análise , Técnicas Biossensoriais/métodos , Monitoramento de Medicamentos/métodos , Agulhas , Penicilina G/análise , Penicilina V/análise , Antibacterianos/química , Técnicas Biossensoriais/instrumentação , Monitoramento de Medicamentos/instrumentação , Técnicas Eletroquímicas/instrumentação , Técnicas Eletroquímicas/métodos , Eletrodos , Humanos , Hidrólise , Irídio/química , Limite de Detecção , Penicilina G/química , Penicilina V/química , Estudo de Prova de Conceito , beta-Lactamases/química
7.
Cochrane Database Syst Rev ; 3: CD011571, 2019 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-30835819

RESUMO

BACKGROUND: Psoriasis is a chronic skin disease that affects approximately two per cent of the general population. Plaque psoriasis is the most common form: it usually appears as raised, red patches of inflamed skin, covered with silvery white scales. The patches often occur in a symmetrical pattern. Guttate psoriasis is a particular form of psoriasis with widespread, small erythematosquamous lesions. Streptococcal infection is suspected to be a triggering factor for the onset of guttate psoriasis, and flare-up of chronic plaque psoriasis. The previous Cochrane Review on this topic was published in 2000; it required an update because antistreptococcal treatment continues to be used to treat psoriasis, especially for the acute form of guttate psoriasis. OBJECTIVES: To assess the effects of antistreptococcal interventions for guttate and chronic plaque psoriasis. SEARCH METHODS: We searched Cochrane Skin Specialised Register, Cochrane Register of Studies Online, CENTRAL, MEDLINE, Embase, LILACS, and five trials registers (January 2019). We checked the reference lists of included and excluded studies and searched conference proceedings from the American Academy of Dermatology, Society for Investigative Dermatology, and European Academy of Dermatology and Venereology. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) assessing antistreptococcal interventions (tonsillectomy or systemic antibiotic treatment) in people with clinically diagnosed acute guttate and chronic plaque psoriasis compared with placebo, no intervention, or each other. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Primary outcome measures were: 1) time-to-resolution; achieving clear or almost clear skin (Physician Global Assessment (PGA) 0 or 1 or Psoriasis Area and Severity Index (PASI) 90 or 100); 2) proportion of participants with adverse effects and severe adverse effects. Secondary outcomes were: 1) proportion of participants achieving clear or almost clear skin; 2) proportion of participants achieving PASI 75 or PGA 1 to 2; 3) risk of having at least one relapse at long-term follow-up. Short-term assessment was defined as within eight weeks of the start of treatment; long-term was at least one year after the start of treatment. MAIN RESULTS: We included five trials (162 randomised participants); three were conducted in a hospital dermatology department. One study declared funding by a pharmaceutical company. Participants' ages ranged from 12 to 77 years; only two participants were younger than 15 years. Mean PASI score at baseline varied from 5.7 (i.e. mild) to 23 (i.e. severe) in four studies. Twenty-three of 162 participants had streptococcus-positive throat swab culture. We did not perform a meta-analysis due to heterogeneity of participants' characteristics and interventions.None of the trials measured our efficacy primary outcome, time-to-resolution, or the secondary outcome, risk of having at least one relapse at long-term follow-up.We rated the quality of the results as very low-quality evidence, due to high risk of bias (absence of blinding of participants and caregivers, and high risk of outcome reporting bias) and imprecision (single study data with a low number of events). Hence, we are very uncertain about the results presented.Guttate psoriasisOne three-armed trial (N = 43) assessed penicillin (50,000 international units (IU)/kg/day in three doses) versus erythromycin (250 mg four times per day) versus no treatment (treatment for 14 days, with six-week follow-up from start of treatment). Adverse events and the proportion of participants achieving clear or almost clear skin were not measured.One trial (N = 20) assessed penicillin (1.6 MU (million units) intramuscularly once a day) versus no treatment (six weeks of treatment, with eight-week follow-up from start of treatment). At six-week (short-term) follow-up, no adverse events were observed in either group, and there was no statistically significant difference between the two groups in the proportion of participants with clear or almost clear skin (risk ratio (RR) 2.00, 95% confidence interval (CI) 0.68 to 5.85).One trial (N = 20) assessed rifampicin (300 mg twice daily) versus placebo (14-day treatment duration; six-week follow-up from start of treatment); none of the review outcomes were measured.These trials did not measure the proportion of participants achieving PASI 75 or PGA 1 to 2.Chronic plaque psoriasisOne trial (N = 50) assessed long-term azithromycin treatment (500 mg daily dose) versus vitamin C. Adverse events were reported in the azithromycin group (10 out of 30 had nausea and mild abdominal upset), but not in the vitamin C group. The proportion of participants who achieved clear or almost clear skin was not measured. In the azithromycin group, 18/30 versus 0/20 participants in the vitamin C group reached PASI 75 at the end of 48 weeks of treatment (RR 25.06, 95% CI 1.60 to 393.59).One trial (N = 29) assessed tonsillectomy versus no treatment, with 24-month follow-up after surgery. One participant in the tonsillectomy group had minor bleeding. At eight-week follow-up, 1/15 in the tonsillectomy group, and 0/14 in the no treatment group achieved PASI 90; and 3/15 participants in the tonsillectomy group, and 0/14 in the no treatment group achieved PASI 75 (RR 6.56, 95% CI 0.37 to 116.7). AUTHORS' CONCLUSIONS: We found only five trials (N = 162), which assessed the effects of five comparisons (systemic antibiotic treatment (penicillin, azithromycin) or tonsillectomy). Two comparisons (erythromycin compared to no treatment, and rifampicin compared to placebo) did not measure any of the outcomes of interest. There was very low-quality evidence for the outcomes that were measured, Therefore, we are uncertain of both the efficacy and safety of antistreptococcal interventions for guttate and chronic plaque psoriasis.The included trials were at unclear or high risk of bias and involved only a small number of unrepresentative participants, with limited measurement of our outcomes of interest. The studies did not allow investigation into the influence of Streptococcal infection, and a key intervention (amoxicillin) was not assessed.Further trials assessing the efficacy and tolerance of penicillin V or amoxicillin are needed in children and young adults with guttate psoriasis.


Assuntos
Antibacterianos/uso terapêutico , Psoríase/tratamento farmacológico , Infecções Estreptocócicas/tratamento farmacológico , Adolescente , Adulto , Idoso , Ácido Ascórbico/uso terapêutico , Azitromicina/uso terapêutico , Criança , Eritromicina/uso terapêutico , Humanos , Pessoa de Meia-Idade , Penicilina V/uso terapêutico , Psoríase/microbiologia , Psoríase/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Rifampina/uso terapêutico , Tonsilectomia , Vitaminas/uso terapêutico
8.
J Pharm Sci ; 108(3): 1227-1235, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30385287

RESUMO

Overencapsulation is a technique used to conceal tablet products for blinding in randomized controlled trials. A tablet is inserted in an opaque capsule shell with backfill excipient to prevent rattling. Regulatory authorities require evidence that such modification does not materially alter drug release to approve their use in trials. The objective of this study was to assess impact of overencapsulation on disintegration and dissolution of 4 immediate-release drug products (penicillin V, gemfibrozil, ciprofloxacin, and furosemide). Each unmodified tablet was compared to 3 overencapsulated tablets with differing backfill excipient (colloidal silica, lactose monohydrate, or microcrystalline cellulose). All 12 overencapsulated tablets met disintegration and dissolution acceptance criteria. Dissolution acceptance was dependent on apparatus as only 4/12 formulations met specifications using the rotating basket compared to 12/12 using the rotating paddle. Significant differences in release were observed at early time points (T5-T15). No correlation was observed between aqueous solubility and release, although dissolution of the lipophilic drug gemfibrozil was least impacted by overencapsulation. There was evidence that type/quantity of backfill delays release at early time points. These findings indicate that under the specified conditions, overencapsulated formulations of 4 drugs, 1 from each class of the Biopharmaceutics Classification System, met compendial requirements for release testing.


Assuntos
Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Excipientes/química , Ensaios Clínicos Controlados Aleatórios como Assunto , Química Farmacêutica , Ciprofloxacino/química , Ciprofloxacino/farmacocinética , Furosemida/química , Furosemida/farmacocinética , Genfibrozila/química , Genfibrozila/farmacocinética , Penicilina V/química , Penicilina V/farmacocinética , Solubilidade , Comprimidos
9.
Sci Total Environ ; 651(Pt 1): 1605-1612, 2019 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-30360286

RESUMO

߭Lactam antibiotics are among the most widely used antibiotics in human medicine and their effects on the aquatic environment - concerning bacterial resistance - are controversially discussed. This study focused on the photolysis of the four ߭lactam antibiotics - amoxicillin, ampicillin, penicillin V and piperacillin - under simulated environmental conditions. It was observed that all investigated ߭lactam antibiotics are photolytically degradable by simulated sunlight (1 kW/m2) with half-lives between 3.2 and 7.0 h. Structure elucidation of transformation products performed with liquid chromatography coupled to high resolution mass spectrometry showed that the hydrolysis of the ߭lactam ring is the primary transformation reaction, followed by the elimination of carboxylic and dimethyl thiazolidine carboxylic acid. Growth inhibition tests on Bacillus subtilis showed the loss of bactericide activity of irradiated solutions of amoxicillin, ampicillin and piperacillin, suggesting the transformation of the ߭lactam ring is responsible for the antibiotic effect. In contrast, the solutions of penicillin V did not show any decline of the antibacterial activity after photolytic degradation, probably due to the formation of still active epimers.


Assuntos
Antibacterianos/química , Fotólise , Eliminação de Resíduos Líquidos , Poluentes Químicos da Água/química , beta-Lactamas/química , Amoxicilina/química , Amoxicilina/farmacologia , Ampicilina/química , Ampicilina/farmacologia , Antibacterianos/farmacologia , Biodegradação Ambiental , Penicilina V/química , Penicilina V/farmacologia , Piperacilina/química , Piperacilina/farmacologia , Luz Solar , beta-Lactamas/farmacologia
10.
Int J STD AIDS ; 30(1): 82-85, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30114994

RESUMO

Congenital syphilis is a prevalent infection in much of the world but rare in contexts where antenatal screening and treatment are available. In the UK in 2016, three cases of congenital syphilis were reported in babies born to women who were seronegative at the time of booking and hence a high degree of clinical vigilance is required in the unwell infant. We present the case of a seven-week-old baby girl with congenital syphilis with the unusual finding of discrete liver lesions. This baby was successfully treated with intravenous ceftriaxone.


Assuntos
Ossos da Extremidade Inferior/diagnóstico por imagem , Fígado/diagnóstico por imagem , Complicações Infecciosas na Gravidez/diagnóstico , Sífilis Congênita/diagnóstico , Treponema pallidum/isolamento & purificação , Administração Intravenosa , Administração Oral , Biópsia , Ceftriaxona/uso terapêutico , Feminino , Humanos , Recém-Nascido , Imagem por Ressonância Magnética , Penicilina V/uso terapêutico , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Sífilis Congênita/sangue , Sífilis Congênita/tratamento farmacológico , Resultado do Tratamento , Treponema pallidum/genética , Ultrassonografia
11.
Aten Primaria ; 51(1): 32-39, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-29061311

RESUMO

INTRODUCTION: Community-acquired pneumonia (CAP) is treated with penicillin in some northern European countries. OBJECTIVES: To evaluate whether high-dose penicillin V is as effective as high-dose amoxicillin for the treatment of non-severe CAP. DESIGN: Multicentre, parallel, double-blind, controlled, randomized clinical trial. SETTING: 31 primary care centers in Spain. PARTICIPANTS: Patients from 18 to 75 years of age with no significant associated comorbidity and with symptoms of lower respiratory tract infection and radiological confirmation of CAP were randomized to receive either penicillin V 1.6 million units, or amoxicillin 1000mg three times per day for 10 days. MAIN MEASUREMENTS: The main outcome was clinical cure at 14 days, and the primary hypothesis was that penicillin V would be non-inferior to amoxicillin with regard to this outcome, with a margin of 15% for the difference in proportions. EudraCT register 2012-003511-63. RESULTS: A total of 43 subjects (amoxicillin: 28; penicillin: 15) were randomized. Clinical cure was observed in 10 (90.9%) patients assigned to penicillin and in 25 (100%) patients assigned to amoxicillin with a difference of -9.1% (95% CI, -41.3% to 6.4%; p=.951) for non-inferiority. In the intention-to-treat analysis, amoxicillin was found to be 28.6% superior to penicillin (95% CI, 7.3-58.1%; p=.009 for superiority). The number of adverse events was similar in both groups. CONCLUSIONS: There was a trend favoring high-dose amoxicillin versus high-dose penicillin in adults with uncomplicated CAP. The main limitation of this trial was the low statistical power due to the low number of patients included.


Assuntos
Amoxicilina/administração & dosagem , Antibacterianos/administração & dosagem , Penicilina V/administração & dosagem , Pneumonia/tratamento farmacológico , Adulto , Idoso , Amoxicilina/efeitos adversos , Antibacterianos/efeitos adversos , Infecções Comunitárias Adquiridas/tratamento farmacológico , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Penicilina V/efeitos adversos , Estudos Prospectivos , Espanha , Resultado do Tratamento
12.
Pak J Pharm Sci ; 31(4(Special)): 1633-1638, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30203751

RESUMO

In order to conceal the unpleasant smell of pharmaceutical raw materials of Penicillin V potassium, we use ß-cyclodextrin (ß-CD) as a drug carrier. The Penicillin V potassium ß-CD inclusion complex was prepared by saturated aqueous solution method; the characterization of penicillin V potassium ß-CD inclusion complex is determined by scanning electron microscopy, Differential Scanning Calorimeter (DSC) and X-ray Diffraction (XRD), the formation constants of the complexes were determined by UV spectrophotometry; based on the results obtained from the orthogonal experimental design, the optimum preparation process are summarized as follow: ß-CD: Penicillin V potassium = 4: 1 (molar ratio), stirring temperature 50 centigrade, stirring time 12h, the encapsulation efficiency is 29.40%.


Assuntos
Cristalização/métodos , Portadores de Fármacos/química , Penicilina V/química , beta-Ciclodextrinas/química , Temperatura , Fatores de Tempo
13.
Cochrane Database Syst Rev ; 9: CD010136, 2018 09 27.
Artigo em Inglês | MEDLINE | ID: mdl-30259968

RESUMO

BACKGROUND: Dental pain can have a detrimental effect on quality of life. Symptomatic apical periodontitis and acute apical abscess are common causes of dental pain and arise from an inflamed or necrotic dental pulp, or infection of the pulpless root canal system. Clinical guidelines recommend that the first-line treatment for teeth with these conditions should be removal of the source of inflammation or infection by local, operative measures, and that systemic antibiotics are currently only recommended for situations where there is evidence of spreading infection (cellulitis, lymph node involvement, diffuse swelling) or systemic involvement (fever, malaise). Despite this, there is evidence that dentists frequently prescribe antibiotics in the absence of these signs. There is concern that this could contribute to the development of antibiotic-resistant bacterial colonies within both the individual and the community. This review is an update of the original version that was published in 2014. OBJECTIVES: To evaluate the effects of systemic antibiotics provided with or without surgical intervention (such as extraction, incision and drainage of a swelling, or endodontic treatment), with or without analgesics, for symptomatic apical periodontitis and acute apical abscess in adults. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 26 February 2018), the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 1) in the Cochrane Library (searched 26 February 2018), MEDLINE Ovid (1946 to 26 February 2018), Embase Ovid (1980 to 26 February 2018), and CINAHL EBSCO (1937 to 26 February 2018). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. A grey literature search was conducted using OpenGrey (to 26 February 2018) and ZETOC Conference Proceedings (1993 to 26 February 2018). No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: Randomised controlled trials of systemic antibiotics in adults with a clinical diagnosis of symptomatic apical periodontitis or acute apical abscess, with or without surgical intervention (considered in this situation to be extraction, incision and drainage or endodontic treatment) and with or without analgesics. DATA COLLECTION AND ANALYSIS: Two authors screened the results of the searches against inclusion criteria, extracted data and assessed risk of bias independently and in duplicate. We calculated mean differences (MD) (standardised mean difference (SMD) when different scales were reported) and 95% confidence intervals (CI) for continuous data. A fixed-effect model was used in the meta-analysis as there were fewer than four studies. We contacted study authors to obtain missing information. MAIN RESULTS: We included two trials in this review, with 62 participants included in the analyses. Both trials were conducted in university dental schools in the USA and compared the effects of oral penicillin V potassium (penicillin VK) versus a matched placebo when provided in conjunction with a surgical intervention (total or partial pulpectomy) and analgesics to adults with acute apical abscess or symptomatic necrotic tooth. The patients included in these trials had no signs of spreading infection or systemic involvement (fever, malaise). We assessed one study as having a high risk of bias and the other study as having unclear risk of bias.The primary outcome variables reported in both studies were participant-reported pain and swelling (one trial also reported participant-reported percussion pain). One study reported the type and number of analgesics taken by participants. One study recorded the incidence of postoperative endodontic flare-ups (people who returned with symptoms that necessitated further treatment). Adverse effects, as reported in one study, were diarrhoea (one participant, placebo group) and fatigue and reduced energy postoperatively (one participant, antibiotic group). Neither study reported quality of life measurements.Objective 1: systemic antibiotics versus placebo with surgical intervention and analgesics for symptomatic apical periodontitis or acute apical abscessTwo studies provided data for the comparison between systemic antibiotics (penicillin VK) and a matched placebo for adults with acute apical abscess or a symptomatic necrotic tooth when provided in conjunction with a surgical intervention. Participants in one study all underwent a total pulpectomy of the affected tooth, while participants in the other study had their tooth treated by either partial or total pulpectomy. Participants in both trials received oral analgesics. There were no statistically significant differences in participant-reported measures of pain or swelling at any of the time points assessed within the review. The MD for pain (short ordinal numerical scale 0 to 3) was -0.03 (95% CI -0.53 to 0.47) at 24 hours; 0.32 (95% CI -0.22 to 0.86) at 48 hours; and 0.08 (95% CI -0.38 to 0.54) at 72 hours. The SMD for swelling was 0.27 (95% CI -0.23 to 0.78) at 24 hours; 0.04 (95% CI -0.47 to 0.55) at 48 hours; and 0.02 (95% CI -0.49 to 0.52) at 72 hours. The body of evidence was assessed as at very low quality.Objective 2: systemic antibiotics without surgical intervention for adults with symptomatic apical periodontitis or acute apical abscessWe found no studies that compared the effects of systemic antibiotics with a matched placebo delivered without a surgical intervention for symptomatic apical periodontitis or acute apical abscess in adults. AUTHORS' CONCLUSIONS: There is very low-quality evidence that is insufficient to determine the effects of systemic antibiotics on adults with symptomatic apical periodontitis or acute apical abscess.


Assuntos
Antibacterianos/uso terapêutico , Penicilina V/uso terapêutico , Abscesso Periapical/tratamento farmacológico , Periodontite Periapical/tratamento farmacológico , Doença Aguda , Adulto , Humanos , Abscesso Periapical/cirurgia , Periodontite Periapical/cirurgia , Pulpectomia/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto , Odontalgia/tratamento farmacológico
14.
BMJ Case Rep ; 20182018 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-30158261

RESUMO

Hepatic hydrothorax refers to the presence of a pleural effusion (usually >500 mL) in a patient with cirrhosis in whom other causes of pleural effusion, such as cardiopulmonary causes, pleural disease or malignancy have been excluded. It is seen in 5%-10% of patients with end-stage liver disease. A subset of these patients can develop infection of the hepatic hydrothorax, called spontaneous bacterial empyema. They may present with fever, chills and dyspnoea. We present the case of an 83-year-old man with a history of cirrhosis who developed a large right-sided pleural effusion, confirmed to be empyema by pleural fluid analysis. We aim to highlight the occurrence of spontaneous bacterial empyema. While less common that spontaneous bacterial peritonitis as a complication of cirrhosis, it is equally serious with potential for adverse outcomes.


Assuntos
Empiema Pleural/diagnóstico , Cirrose Hepática , Derrame Pleural/diagnóstico , Infecções Estreptocócicas/diagnóstico , Streptococcus pyogenes , Idoso de 80 Anos ou mais , Terapia Combinada , Diagnóstico Diferencial , Empiema Pleural/complicações , Empiema Pleural/diagnóstico por imagem , Empiema Pleural/terapia , Humanos , Masculino , Penicilina V/administração & dosagem , Penicilina V/uso terapêutico , Derrame Pleural/complicações , Derrame Pleural/diagnóstico por imagem , Derrame Pleural/terapia , Radiografia Torácica , Infecções Estreptocócicas/complicações , Infecções Estreptocócicas/diagnóstico por imagem , Infecções Estreptocócicas/terapia , Toracentese
15.
Clin Microbiol Infect ; 24(12): 1290-1296, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29505880

RESUMO

OBJECTIVES: To compare the three most commonly used antibiotics for erythema migrans (EM) in Norwegian primary care. METHODS: A randomized, parallel, controlled trial was carried out. Treatments were open to the patients, but blinded for the GPs and investigators. Patients eligible for inclusion were aged ≥18 years and clinically diagnosed with EM. Block randomization was processed in blocks of six. Patients were assigned to receive one of three antibiotic treatments for 14 days: phenoxymethylpenicillin (PCV), amoxicillin, or doxycycline. The primary outcome was the duration of EM in days in the three treatment groups. Patients kept a diary for the 14 days of treatment, in which they registered concomitant symptoms and side effects. The patients consulted their GP after 14 days of treatment and had a 1-year follow-up to monitor any development of disseminated Lyme borreliosis (LB). EMs with a duration of more than 14 days were followed until resolution. ClinicalTrials.govNCT01368341 and EU Clinical Trials Register 2010-023747-15. RESULTS: One hundred and eighty eight patients (PCV: n = 56, amoxicillin: n = 64, doxycycline: n = 68) were included by 44 Norwegian general practitioners (GPs) from June 2011 to November 2013. Follow-up was completed by December 2014. The median duration of EM was altogether 14 days (range 3-293). For the PCV group median duration was 14 days (range 5-91), for amoxicillin 13 days (range 4-179) and for doxycycline 14 days (range 3-293). The duration of EM did not differ significantly between the three antibiotic groups (p 0.277). None of the patients developed disseminated LB within the 1-year follow-up. CONCLUSIONS: We did not find 14 days of PCV, doxycycline, and amoxicillin treatments to differ in effectiveness or safety in the treatment of clinically diagnosed EM in primary care.


Assuntos
Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Doxiciclina/uso terapêutico , Eritema Migrans Crônico/tratamento farmacológico , Doença de Lyme/tratamento farmacológico , Penicilina V/uso terapêutico , Adolescente , Adulto , Idoso , Amoxicilina/administração & dosagem , Amoxicilina/efeitos adversos , Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Anticorpos Antibacterianos/sangue , Doxiciclina/administração & dosagem , Doxiciclina/efeitos adversos , Eritema Migrans Crônico/epidemiologia , Eritema Migrans Crônico/microbiologia , Feminino , Seguimentos , Medicina Geral/estatística & dados numéricos , Humanos , Imunoglobulina G/sangue , Doença de Lyme/diagnóstico , Doença de Lyme/epidemiologia , Doença de Lyme/microbiologia , Masculino , Pessoa de Meia-Idade , Noruega/epidemiologia , Penicilina V/administração & dosagem , Penicilina V/efeitos adversos , Atenção Primária à Saúde/estatística & dados numéricos , Adulto Jovem
16.
BMJ Open ; 8(2): e019997, 2018 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-29476030

RESUMO

INTRODUCTION AND OBJECTIVES: Macrolides have been associated with proarrhythmic properties, but the evidence is conflicting. We evaluated the risk of out-of-hospital cardiac arrest (OHCA) associated with specific macrolides in a retrospective study. Associations between specific macrolides and OHCA were examined by conditional logistic regression analyses in case-crossover and case-time-control models, using penicillin-V treatment as the comparative reference. From nationwide registries, we identified all OHCAs in Denmark from 2001 to 2010 and use of antibiotics. ETHICS: The present study was approved by the Danish Data Protection Agency (Danish Data Protection Agency (ref.no. 2007-58-0015, local ref.no. GEH-2014-017, (I-Suite.nr. 02 735)). PARTICIPANTS: We identified 29 111 patients with an OHCA. Of these, 514 were in macrolide treatment ≤7 days before OHCA and 1237 in penicillin-V treatment. RESULTS: In the case-crossover analyses, overall macrolide use was not associated with OHCA with penicillin V as negative comparative reference (OR=0.90; 95% CI 0.73 to 1.10). Compared with penicillin-V treatment, specific macrolides were not associated with increased risk of OHCA: roxithromycin (OR=0.97; 95% CI 0.74 to 1.26), erythromycin (OR=0.68; 95% CI 0.44 to 1.06), clarithromycin (OR=0.95; 95% CI 0.61 to 1.48) and azithromycin (OR=0.85; 95% CI 0.57 to 1.27).Similar results were obtained using case-time-control models: overall macrolide use (OR=0.81; 95% CI 0.62 to 1.06) and specific macrolides (roxithromycin (OR=0.70; 95% CI 0.49 to 1.00), erythromycin (OR=0.67; 95% CI 0.38 to 1.18), clarithromycin (OR=0.75; 95% CI 0.41 to 1.39) or azithromycin (OR=1.17; 95% CI 0.70 to 1.95)). CONCLUSION: The risk of OHCA during treatment with macrolides was similar to that of penicillin V, suggesting no additional risk of OHCA associated with macrolides.


Assuntos
Antibacterianos/efeitos adversos , Macrolídeos/efeitos adversos , Parada Cardíaca Extra-Hospitalar/etiologia , Penicilina V/efeitos adversos , Sistemas de Notificação de Reações Adversas a Medicamentos , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos Cross-Over , Bases de Dados Factuais , Dinamarca , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Parada Cardíaca Extra-Hospitalar/prevenção & controle , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
18.
Pediatr Infect Dis J ; 37(11): 1112-1117, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-29474259

RESUMO

BACKGROUND: In Denmark, the use of amoxicillin is widespread among children, despite phenoxymethylpenicillin being recommended as first-line therapy. The reason for this apparent discrepancy is not fully understood. We aimed at evaluating prescribing patterns of antibiotics among Danish children 0-4 years of age, with emphasis on incidence of treatment episodes, choice of initial antibiotic treatment and switching patterns between different types of antibiotics. METHODS: We identified all children ≤4 years of age who filled a prescription of antibiotics from 2000 to 2015 according to the nationwide Danish National Prescription Registry. We estimated the incidence rate of episodes treated with antibiotics and the choice of initial antibiotic treatment over time. Further, we assessed the cumulative risk of switching within 0-3 days after initiating therapy. RESULTS: We identified 3,481,684 antibiotic treatment episodes issued to 0- to 4-year-olds from 2000 to 2015. The incidence rate was stable until 2011 both among children 0-1 years of age (approximately 880/1000) and among children 2-4 years of age (approximately 610/1000), after which it dropped. Phenoxymethylpenicillin and, increasingly, amoxicillin were most frequently used as initial treatments (39% vs. 44%). Few switched from amoxicillin (1%) or phenoxymethylpenicillin (4.7%) within the first 3 days. Of those who switched from phenoxymethylpenicillin, 64% received amoxicillin as second-line treatment. CONCLUSIONS: The incidence of episodes treated with antibiotics among Danish children 0-4 years of age has decreased considerably since 2011. In contrast to guideline recommendations, amoxicillin is the most frequently used initial treatment. Early switching between antibiotics is uncommon. Initiatives should address the extensive use of amoxicillin.


Assuntos
Prescrições de Medicamentos/estatística & dados numéricos , Substituição de Medicamentos/estatística & dados numéricos , Uso de Medicamentos , Padrões de Prática Médica/estatística & dados numéricos , Amoxicilina/uso terapêutico , Antibacterianos/uso terapêutico , Pré-Escolar , Dinamarca , Humanos , Lactente , Recém-Nascido , Penicilina V/uso terapêutico
19.
Eur J Clin Microbiol Infect Dis ; 37(2): 355-361, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29218467

RESUMO

Comparative information on diagnosis-related antibiotic prescribing patterns are scarce from primary care within and between countries. To describe and compare antibiotic prescription and routine management of infections in primary care in Latvia (LV), Lithuania (LT) and two study sites in Sweden (SE), a cross-sectional observational study on patients who consulted due to sypmtoms compatible with infection was undetraken. Infection and treatment was detected and recorded by physicians only. Data was collected from altogether 8786 consecutive patients with infections in the three countries. Although the overall proportion of patients receiving an antibiotic prescription was similar in all three countries (LV and LT 42%, SE 38%), there were differences in the rate of prescription between the countries depending on the respective diagnoses. While penicillins dominated among prescriptions (LV 58%, LT 67%, SE 70%), phenoxymethylpenicillin was most commonly prescribed in Sweden (57% of all penicillins), while it was amoxicillin with or without clavulanic acid in Latvia (99%) and Lithuania (85%) respectively. Pivmecillinam and flucloxacillin, which accounted for 29% of penicillins in Sweden, were available neither in Latvia nor in Lithuania. The applied methodology was simple, and provided useful information on differences in treatment of common infections in ambulatory care in the absence of available computerized diagnosis-prescription data. Despite some limitations, the method can be used for assessment of intention to treat and compliance to treatment guidelines and benchmarking locally, nationally, or internationally, just as the point prevalence surveys (PPS) protocols have been used in hospitals all over Europe.


Assuntos
Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Prescrições de Medicamentos/estatística & dados numéricos , Clínicos Gerais/estatística & dados numéricos , Padrões de Prática Médica/estatística & dados numéricos , Adulto , Andinocilina Pivoxil/uso terapêutico , Amoxicilina/uso terapêutico , Ácido Clavulânico/uso terapêutico , Estudos Transversais , Feminino , Floxacilina/uso terapêutico , Humanos , Letônia , Lituânia , Masculino , Penicilina V/uso terapêutico , Suécia , Adulto Jovem
20.
Am J Forensic Med Pathol ; 39(1): 14-17, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29135492

RESUMO

Anaphylaxis can be difficult to diagnose in the postmortem setting. Postmortem tryptase is a widely used ancillary test in aiding the diagnosis in which an elevation supports a death from anaphylaxis. Postmortem tryptase can be difficult to interpret, and the effects of postmortem kinetics are not fully understood. Clinically, mast cell tryptase returns to baseline 24 to 72 hours after an anaphylactic stimulus. We report another anaphylactic death from antibiotic administration in which 2 serial postmortem total tryptase measurements at 3 days (72 hours) and 6 days (144 hours) after death declined from 522 µg/L to 300 µg/L (baseline, 5.6 µg/L). The declination appears to be slower than what is expected in the clinical setting. This case highlights yet another example of the difficult and complex interaction of postmortem interval on postmortem tryptase, especially in an anaphylactic death. We suggest that early blood sampling and serial tests be performed if possible in suspected anaphylactic death.


Assuntos
Anafilaxia/sangue , Antibacterianos/efeitos adversos , Penicilina G/efeitos adversos , Mudanças Depois da Morte , Triptases/sangue , Idoso , Anafilaxia/induzido quimicamente , Antibacterianos/imunologia , Humanos , Imunoglobulina E/sangue , Masculino , Penicilina G/imunologia , Penicilina V/imunologia
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