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1.
Gastroenterology ; 157(3): 682-691.e2, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31152740

RESUMO

BACKGROUND & AIMS: Proton pump inhibitors (PPIs) are effective at treating acid-related disorders. These drugs are well tolerated in the short term, but long-term treatment was associated with adverse events in observational studies. We aimed to confirm these findings in an adequately powered randomized trial. METHODS: We performed a 3 × 2 partial factorial double-blind trial of 17,598 participants with stable cardiovascular disease and peripheral artery disease randomly assigned to groups given pantoprazole (40 mg daily, n = 8791) or placebo (n = 8807). Participants were also randomly assigned to groups that received rivaroxaban (2.5 mg twice daily) with aspirin (100 mg once daily), rivaroxaban (5 mg twice daily), or aspirin (100 mg) alone. We collected data on development of pneumonia, Clostridium difficile infection, other enteric infections, fractures, gastric atrophy, chronic kidney disease, diabetes, chronic obstructive lung disease, dementia, cardiovascular disease, cancer, hospitalizations, and all-cause mortality every 6 months. Patients were followed up for a median of 3.01 years, with 53,152 patient-years of follow-up. RESULTS: There was no statistically significant difference between the pantoprazole and placebo groups in safety events except for enteric infections (1.4% vs 1.0% in the placebo group; odds ratio, 1.33; 95% confidence interval, 1.01-1.75). For all other safety outcomes, proportions were similar between groups except for C difficile infection, which was approximately twice as common in the pantoprazole vs the placebo group, although there were only 13 events, so this difference was not statistically significant. CONCLUSIONS: In a large placebo-controlled randomized trial, we found that pantoprazole is not associated with any adverse event when used for 3 years, with the possible exception of an increased risk of enteric infections. ClinicalTrials.gov Number: NCT01776424.


Assuntos
Aspirina/administração & dosagem , Doenças Cardiovasculares/tratamento farmacológico , Inibidores do Fator Xa/administração & dosagem , Hemorragia Gastrointestinal/prevenção & controle , Pantoprazol/administração & dosagem , Doença Arterial Periférica/tratamento farmacológico , Inibidores da Agregação de Plaquetas/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Rivaroxabana/administração & dosagem , Idoso , Aspirina/efeitos adversos , Doenças Cardiovasculares/diagnóstico , Método Duplo-Cego , Esquema de Medicação , Enterocolite Pseudomembranosa/induzido quimicamente , Enterocolite Pseudomembranosa/microbiologia , Inibidores do Fator Xa/efeitos adversos , Feminino , Hemorragia Gastrointestinal/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Pantoprazol/efeitos adversos , Doença Arterial Periférica/diagnóstico , Inibidores da Agregação de Plaquetas/efeitos adversos , Estudos Prospectivos , Inibidores da Bomba de Prótons/efeitos adversos , Medição de Risco , Fatores de Risco , Rivaroxabana/efeitos adversos , Fatores de Tempo , Resultado do Tratamento
2.
Medicine (Baltimore) ; 98(13): e15004, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30921218

RESUMO

RATIONALE: Clostridium difficile-associated diarrhea (CDAD) remains a persistent challenge, with substantially increased incidence and severity. The rising burden of CDAD requires urgent identification of preventable risk factors. PATIENTS CONCERNS: A 77-year-old man with the symptoms of abdominal pain and watery diarrhea was readmitted to the hospital, who received cephalosporins and proton pump inhibitors (PPIs) during the initial hospitalization for 12 days until discharge. Antibiotic-associated diarrhea was seriously suspected. And the stool sample was immediately sent for inspection for C difficile. He had a history of chronic bronchitis, coronary heart disease, and osteonecrosis. DIAGNOSIS: CDAD, renal insufficiency INTERVENTIONS:: Oral vancomycin was administered for 14 days. OUTCOMES: On the third day after readmission, the stool sample turned out to be positive for both C difficile toxin and its antigen. After 10-day treatment with vancomycin, diarrhea symptoms disappeared and his stools became normal. LESSONS: In elderly patients with multiple comorbidities, PPIs must be administered cautiously to minimize the risk for adverse effects including CDAD. It is important to identify the preventable risk factors of CDAD for clinicians and pharmacists. Oral vancomycin therapy seems to be effective in CDAD.


Assuntos
Antibacterianos/efeitos adversos , Clostridium difficile , Diarreia/induzido quimicamente , Enterocolite Pseudomembranosa/induzido quimicamente , Inibidores da Bomba de Prótons/efeitos adversos , Idoso , Antibacterianos/uso terapêutico , Comorbidade , Diarreia/tratamento farmacológico , Enterocolite Pseudomembranosa/tratamento farmacológico , Humanos , Masculino , Vancomicina/uso terapêutico
3.
Nutrients ; 10(5)2018 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-29701662

RESUMO

Background: Over 70% of patients are prescribed antibiotics during their intensive care (ICU) admission. The gut microbiome is dramatically altered early in an ICU stay, increasing the risk for antibiotic associated diarrhea (AAD) and Clostridium difficile infections (CDI). Evidence suggests that some probiotics are effective in the primary prevention of AAD and CDI. Aim: To demonstrate safety and feasibility of a probiotic drink in ICU patients. Methods: ICU patients initiated on antibiotics were recruited, and matched with contemporary controls. Study patients received two bottles daily of a drink containing 10 billion Lactobacillus casei which was bolused via feeding tube. Tolerance to probiotics and enteral nutrition, development of adverse events, and incidence of AAD was recorded. CDI rates were followed for 30 days post antibiotic treatment. Results: Thirty-two patients participated in the trial. There were no serious adverse events in the probiotic group, compared to three in the control group. AAD was documented in 12.5% of the probiotic group and 31.3% in the control group. One patient in the probiotic group developed CDI compared to three in the control group. Discussion: A probiotic containing drink can safely be delivered via feeding tube and should be considered as a preventative measure for AAD and CDI in ICU.


Assuntos
Antibacterianos/efeitos adversos , Bebidas , Diarreia/prevenção & controle , Enterocolite Pseudomembranosa/prevenção & controle , Microbioma Gastrointestinal , Intestinos/microbiologia , Lactobacillus casei/fisiologia , Probióticos/administração & dosagem , Iogurte/microbiologia , Adulto , Idoso , Alberta , Bebidas/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/microbiologia , Nutrição Enteral , Enterocolite Pseudomembranosa/induzido quimicamente , Enterocolite Pseudomembranosa/microbiologia , Estudos de Viabilidade , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Probióticos/efeitos adversos , Iogurte/efeitos adversos
4.
Curr Opin Gastroenterol ; 34(1): 11-18, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29095766

RESUMO

PURPOSE OF REVIEW: The rising burden of Clostridium difficile infection (CDI) requires urgent identification of preventable risk factors. Observational studies suggest an association between proton-pump inhibitor (PPI) use and CDI risk. RECENT FINDINGS: Key historical literature on PPI and CDI associations is reviewed as a prelude to evaluating the plausibility of a causative association. Impactful literature from the past 18 months is examined in detail and critically appraised through the lens of the Bradford Hill Criteria for determination of causality. The PPI and CDI association has been studied extensively and is valid. Nonetheless, causality is not proven due to extensive and difficult to control confounding in observational studies of CDI patient populations with complex comorbidities. SUMMARY: In the authors' opinion, systematic discontinuation of PPIs in patients at risk for CDI is not warranted based on current evidence. Well controlled prospective human studies are needed. Careful and repeated consideration should be given to all PPI prescriptions to avoid potential adverse effects.


Assuntos
Antibacterianos/efeitos adversos , Clostridium difficile/efeitos dos fármacos , Enterocolite Pseudomembranosa/induzido quimicamente , Inibidores da Bomba de Prótons/efeitos adversos , Antibacterianos/uso terapêutico , Enterocolite Pseudomembranosa/prevenção & controle , Humanos , Incidência , Estudos Observacionais como Assunto , Padrões de Prática Médica , Inibidores da Bomba de Prótons/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Recidiva , Fatores de Risco
5.
J Biol Chem ; 292(47): 19503-19520, 2017 11 24.
Artigo em Inglês | MEDLINE | ID: mdl-28972161

RESUMO

Cytotoxin-producing Klebsiella oxytoca is the causative agent of antibiotic-associated hemorrhagic colitis (AAHC). Recently, the cytotoxin associated with AAHC was identified as tilivalline, a known pentacyclic pyrrolobenzodiazepine (PBD) metabolite produced by K. oxytoca Although this assertion of tilivalline's role in AAHC is supported by evidence from animal experiments, some key aspects of this finding appear to be incompatible with toxicity mechanisms of known PBD toxins. We therefore hypothesized that K. oxytoca may produce some other uncharacterized cytotoxins. To address this question, we investigated whether tilivalline alone is indeed necessary and sufficient to induce cytotoxicity or whether K. oxytoca also produces other cytotoxins. LC-MS- and NMR-based metabolomic analyses revealed the presence of an abundant tricyclic PBD, provisionally designated kleboxymycin, in the supernatant of toxigenic K. oxytoca strains. Moreover, by generating multiple mutants with gene deletions affecting tilivalline biosynthesis, we show that a tryptophanase-deficient, tilivalline-negative K. oxytoca mutant induced cytotoxicity in vitro similar to tilivalline-positive K. oxytoca strains. Furthermore, synthetic kleboxymycin exhibited greater than 9-fold higher cytotoxicity than tilivalline in TC50 cell culture assays. We also found that the biosynthetic pathways for kleboxymycin and tilivalline appear to overlap, as tilivalline is an indole derivative of kleboxymycin. In summary, our results indicate that tilivalline is not essential for inducing cytotoxicity observed in K. oxytoca-associated AAHC and that kleboxymycin is a tilivalline-related bacterial metabolite with even higher cytotoxicity.


Assuntos
Apoptose/efeitos dos fármacos , Benzodiazepinonas/farmacologia , Citotoxinas/farmacologia , Enterocolite Pseudomembranosa/patologia , Klebsiella oxytoca/metabolismo , Neoplasias Laríngeas/patologia , Antibacterianos/efeitos adversos , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/microbiologia , Carcinoma de Células Escamosas/patologia , Enterocolite Pseudomembranosa/induzido quimicamente , Enterocolite Pseudomembranosa/microbiologia , Humanos , Infecções por Klebsiella/tratamento farmacológico , Infecções por Klebsiella/microbiologia , Klebsiella oxytoca/efeitos dos fármacos , Neoplasias Laríngeas/tratamento farmacológico , Neoplasias Laríngeas/microbiologia , Peptídeos/farmacologia , Células Tumorais Cultivadas
6.
BMJ Case Rep ; 20172017 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-28951427

RESUMO

A 35-year-old nulliparous woman underwent uterine artery embolisation (UAE) for heavy menstrual bleeding and anaemia due to fibroids, refractive to medical and surgical treatment.Bilateral UAE was performed after cephazolin prophylaxis and analgesia. Postoperatively, pain and abdominal bloating were prominent. Symptoms were initially treated as postembolisation syndrome, and analgesia was escalated. By the third day, pain was worsening and the woman developed marked tachypnoea and tachycardia, with raised inflammatory markers and lactate. An abdominal X-ray and CT showed dilated colon. A colonoscopy demonstrated severe mucosal ulceration down to the muscular layer.A subtotal colectomy and end ileostomy formation was performed with intraoperative findings of toxic megacolon with near perforation. The cause of the toxic megacolon, in the absence of previous bowel pathology, was attributed to pseudomembranous colitis as a consequence of single dose prophylactic antibiotic.


Assuntos
Antibioticoprofilaxia/efeitos adversos , Colectomia , Enterocolite Pseudomembranosa/induzido quimicamente , Ileostomia , Megacolo Tóxico/induzido quimicamente , Menorragia/cirurgia , Embolização da Artéria Uterina , Adulto , Enterocolite Pseudomembranosa/complicações , Enterocolite Pseudomembranosa/terapia , Feminino , Humanos , Megacolo Tóxico/complicações , Megacolo Tóxico/terapia , Reoperação , Estomas Cirúrgicos , Resultado do Tratamento
7.
Artigo em Inglês | MEDLINE | ID: mdl-28739791

RESUMO

Lowering the gut exposure to antibiotics during treatments can prevent microbiota disruption. We evaluated the effects of an activated charcoal-based adsorbent, DAV131A, on the fecal free moxifloxacin concentration and mortality in a hamster model of moxifloxacin-induced Clostridium difficile infection. A total of 215 hamsters receiving moxifloxacin subcutaneously (day 1 [D1] to D5) were orally infected at D3 with C. difficile spores. They received various doses (0 to 1,800 mg/kg of body weight/day) and schedules (twice a day [BID] or three times a day [TID]) of DAV131A (D1 to D8). Moxifloxacin concentrations and C. difficile counts were determined at D3, and mortality was determined at D12 We compared mortality rates, moxifloxacin concentrations, and C. difficile counts according to DAV131A regimen and modeled the links between DAV131A regimen, moxifloxacin concentration, and mortality. All hamsters that received no DAV131A died, but none of those that received 1,800 mg/kg/day died. Significant dose-dependent relationships between DAV131A dose and (i) mortality, (ii) moxifloxacin concentration, and (iii) C. difficile count were evidenced. Mathematical modeling suggested that (i) lowering the moxifloxacin concentration at D3, which was 58 µg/g (95% confidence interval [CI] = 50 to 66 µg/g) without DAV131A, to 17 µg/g (14 to 21 µg/g) would reduce mortality by 90%; and (ii) this would be achieved with a daily DAV131A dose of 703 mg/kg (596 to 809 mg/kg). In this model of C. difficile infection, DAV131A reduced mortality in a dose-dependent manner by decreasing the fecal free moxifloxacin concentration.


Assuntos
Infecções por Clostridium/induzido quimicamente , Clostridium difficile/patogenicidade , Disbiose/induzido quimicamente , Enterocolite Pseudomembranosa/induzido quimicamente , Fluoroquinolonas/efeitos adversos , Microbioma Gastrointestinal/efeitos dos fármacos , Trato Gastrointestinal/efeitos dos fármacos , Animais , Carvão Vegetal/farmacologia , Infecções por Clostridium/tratamento farmacológico , Cricetinae , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Enterocolite Pseudomembranosa/tratamento farmacológico , Enterocolite Pseudomembranosa/mortalidade , Fluoroquinolonas/farmacologia , Trato Gastrointestinal/microbiologia , Moxifloxacina
8.
Curr Drug Saf ; 12(3): 205-207, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28625146

RESUMO

INTRODUCTION: Incidence of antibiotic- associated diarrhoea is a common (10-30%) but pseudomembranous colitis (PMC) is less frequent (1-5%). Fluoroquinolones, clindamycin, penicillins, cephalosporins (mostly third generation) are commonly associated with PMC. The association between cephalosporins and PMC is now well established. CASE PRESENTATION: A 78 year old male patient developed pseudomembraneous colitis after administration of Ceftriaxone and Cefazoline for the treatment of pleural effusion. The reaction was confirmed by ultrasonography and CT scan. Causative agents were stopped and patient was managed by systemic therapy. Patient was expired due to respiratory complications as there was complexity in management of disease due to development of pseudomembraneous colitis. CONCLUSION: Increase awareness of prescribers for high-risk drugs, close monitoring, with immediate withdrawal of the culprit drug can reduce the complexity of management that occur due to development of such adverse drug reaction.


Assuntos
Antibacterianos/efeitos adversos , Cefalosporinas/efeitos adversos , Enterocolite Pseudomembranosa/induzido quimicamente , Enterocolite Pseudomembranosa/diagnóstico por imagem , Idoso , Antibacterianos/administração & dosagem , Cefazolina/administração & dosagem , Cefazolina/efeitos adversos , Ceftriaxona/administração & dosagem , Ceftriaxona/efeitos adversos , Cefalosporinas/administração & dosagem , Quimioterapia Combinada , Evolução Fatal , Humanos , Masculino
9.
J Pharm Pharmacol ; 69(8): 1033-1040, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28397382

RESUMO

OBJECTIVES: Currently, probiotics are increasingly used as the alternative to antibiotics as well as the preventive measures in humans. In particular, probiotics occupy a key position in the treatment of antibiotics-associated intestinal dysbiosis. A spore-forming microorganism lactobacillus Bacillus coagulans is one of the most promising probiotics. However, some of its pharmacological effects remain poorly understood. This study was aimed at investigation of the effect of B. coagulans (Laktovit Forte) on the intestinal dysbiosis syndrome in mice caused by streptomycin against the background of cyclophosphamide-induced cellular immunodeficiency. METHODS: Pharmacological method: mouse model in vivo with immunodeficiency caused by cyclophosphamide. KEY FINDINGS: In mice with colitis caused by streptomycin treatment, the administration of B. coagulans (Laktovit Forte medicinal product) resulted in an antidiarrhoeal effect, normalisation of gastrointestinal motility and prevention of the animals' weight loss. Given the cyclophosphamide-induced immunosuppression and streptomycin-associated diarrhoea, the immunity was completely restored only under the action of B. coagulans. CONCLUSIONS: According to all parameters, B. coagulans has been proved to be more effective as compared to the Linex Forte reference product containing lacto- and bifidobacteria.


Assuntos
Bacillus coagulans/imunologia , Enterocolite Pseudomembranosa/imunologia , Probióticos/uso terapêutico , Animais , Antidiarreicos/farmacologia , Antidiarreicos/uso terapêutico , Citocinas/antagonistas & inibidores , Citocinas/imunologia , Enterocolite Pseudomembranosa/induzido quimicamente , Enterocolite Pseudomembranosa/tratamento farmacológico , Motilidade Gastrointestinal/efeitos dos fármacos , Motilidade Gastrointestinal/imunologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/imunologia , Masculino , Camundongos , Probióticos/farmacologia , Estreptomicina/toxicidade
10.
JAMA Intern Med ; 177(6): 784-791, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28346595

RESUMO

Importance: Gastric acid suppression has been associated with an increased risk of primary Clostridium difficile infection (CDI), but the risk of recurrent CDI in patients taking gastric acid suppressant medications is unclear. Objective: To perform a systematic review and meta-analysis to evaluate the association between gastric acid suppressants and recurrent CDI. Data Sources: MEDLINE, EMBASE, the Cochrane Central Register, the Cochrane Database, and Web of Science were searched from January 1, 1995, to September 30, 2015, for studies assessing the association between gastric acid suppressant exposure and recurrent CDI. Search terms included Clostridium difficile, pseudomembranous colitis, proton pump inhibitor, and histamine H2 blocker. Study Selection: Case-control studies, cohort studies, and clinical trials that included patients with CDI who did or did not receive gastric acid suppressant therapy and who were evaluated for recurrent CDI were included, with no restriction on study setting (inpatient or outpatient). Data Extraction and Synthesis: The Newcastle-Ottawa scale was used to assess the methodologic quality of included studies. In this scale, case-control and cohort studies were scored on selection, comparability, and ascertainment of the outcome of interest. Data were independently abstracted to a predetermined collection form by 2 investigators. Summary odds ratio estimates with 95% CIs were calculated using the random-effects model and software to calculate the pooled effect size of studies reporting multivariate analyses. Main Outcomes and Measures: Risk of recurrent infection in patients with CDI and its association with use of gastric acid suppressant medication. Results: Sixteen observational studies were included, together reporting 7703 patients with CDI; among these, 1525 patients (19.8%) developed recurrent CDI. The rate of recurrent CDI in patients with gastric acid suppression was 22.1% (892 of 4038 patients) compared with 17.3% (633 of 3665) in patients without gastric acid suppression, which indicated an increased risk by meta-analysis (odds ratio [OR], 1.52; 95% CI, 1.20-1.94; P < .001). There was significant heterogeneity among the studies, with an I2 value of 64%. Subgroup analyses of studies adjusting for age and potential confounders confirmed an increased risk of recurrent CDI with use of gastric acid suppressants (OR, 1.38; 95% CI, 1.08-1.76; P = .02). Conclusions and Relevance: Meta-analyses of observational studies suggest that patients who receive gastric acid suppressants may be at increased risk for recurrent CDI. These data should be interpreted with caution because they may be confounded owing to the observational design of the individual studies. It may be reasonable to re-evaluate the need for these medications in patients with CDI.


Assuntos
Clostridium difficile/efeitos dos fármacos , Enterocolite Pseudomembranosa/induzido quimicamente , Ácido Gástrico/metabolismo , Antagonistas dos Receptores Histamínicos H2/efeitos adversos , Inibidores da Bomba de Prótons/efeitos adversos , Feminino , Antagonistas dos Receptores Histamínicos H2/administração & dosagem , Humanos , Masculino , Inibidores da Bomba de Prótons/administração & dosagem , Fatores de Risco , Índice de Gravidade de Doença
11.
Am J Surg Pathol ; 41(5): 643-654, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28296676

RESUMO

Programmed cell death protein 1 (PD-1) blocking agents are novel immunotherapeutics used for treatment of advanced-stage malignancies. They have shown promise in the treatment of several malignancies, with greater efficacy and better tolerability than cytotoxic T-lymphocyte antigen 4 (CTLA-4) blocking agents. However, as with anti-CTLA-4 agents, clinically significant colitis remains an important complication. Although there is growing awareness of the histopathologic features of anti-CTLA-4 therapy, there is little information on the pathologic features of anti-PD-1 colitis. We describe here the histopathologic findings in 8 patients who developed colitis while on anti-PD-1 monotherapy. The most common pattern of injury observed (5/8 cases) was an active colitis with neutrophilic crypt microabscesses and with prominent crypt epithelial cell apoptosis and crypt atrophy/dropout. These latter features are reminiscent of other colitides with prominent apoptosis such as acute graft-versus-host disease or certain drug-induced colitides. The remainder of cases (3/8) showed a lymphocytic colitis-like pattern, characterized by increased intraepithelial lymphocytes and surface epithelial injury. Apoptosis was also often increased in these cases but crypt atrophy/dropout was not present. In patients who experienced recurrence of anti-PD-1 colitis, histologic features were similar to the initial insult but, in addition, features of chronicity developed that mimicked inflammatory bowel disease (basal lymphoplasmacytosis and crypt architectural irregularity, and Paneth cell metaplasia in 1 case). Awareness of the clinical scenario, however, should allow pathologists to suggest anti-PD-1 colitis. Interestingly, recurrent colitis was observed in patients who had been off anti-PD-1 therapy for many months. As anti-PD-1 agents are increasingly used in oncology, we present this series to increase awareness of anti-PD-1 colitis among pathologists, to facilitate its timely diagnosis and treatment.


Assuntos
Anticorpos/efeitos adversos , Antineoplásicos/efeitos adversos , Colite/induzido quimicamente , Colite/patologia , Colo/efeitos dos fármacos , Colo/patologia , Imunoterapia/efeitos adversos , Receptor de Morte Celular Programada 1/antagonistas & inibidores , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Inflamatórios/uso terapêutico , Apoptose/efeitos dos fármacos , Atrofia , Biópsia , Colectomia , Colite/imunologia , Colite/terapia , Colite Linfocítica/induzido quimicamente , Colite Linfocítica/imunologia , Colite Linfocítica/patologia , Colo/imunologia , Colonoscopia , Diagnóstico Diferencial , Enterocolite Pseudomembranosa/induzido quimicamente , Enterocolite Pseudomembranosa/imunologia , Enterocolite Pseudomembranosa/patologia , Feminino , Humanos , Doenças Inflamatórias Intestinais/patologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Receptor de Morte Celular Programada 1/imunologia , Indução de Remissão , Estudos Retrospectivos , Índice de Gravidade de Doença
14.
World J Gastroenterol ; 22(11): 3078-104, 2016 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-27003987

RESUMO

Antibiotic-associated diarrhea (AAD) and Clostridium difficile infections (CDI) have been well studied for adult cases, but not as well in the pediatric population. Whether the disease process or response to treatments differs between pediatric and adult patients is an important clinical concern when following global guidelines based largely on adult patients. A systematic review of the literature using databases PubMed (June 3, 1978-2015) was conducted to compare AAD and CDI in pediatric and adult populations and determine significant differences and similarities that might impact clinical decisions. In general, pediatric AAD and CDI have a more rapid onset of symptoms, a shorter duration of disease and fewer CDI complications (required surgeries and extended hospitalizations) than in adults. Children experience more community-associated CDI and are associated with smaller outbreaks than adult cases of CDI. The ribotype NAP1/027/BI is more common in adults than children. Children and adults share some similar risk factors, but adults have more complex risk factor profiles associated with more co-morbidities, types of disruptive factors and a wider range of exposures to C. difficile in the healthcare environment. The treatment of pediatric and adult AAD is similar (discontinuing or switching the inciting antibiotic), but other treatment strategies for AAD have not been established. Pediatric CDI responds better to metronidazole, while adult CDI responds better to vancomycin. Recurrent CDI is not commonly reported for children. Prevention for both pediatric and adult AAD and CDI relies upon integrated infection control programs, antibiotic stewardship and may include the use of adjunctive probiotics. Clinical presentation of pediatric AAD and CDI are different than adult AAD and CDI symptoms. These differences should be taken into account when rating severity of disease and prescribing antibiotics.


Assuntos
Antibacterianos/efeitos adversos , Clostridium difficile/efeitos dos fármacos , Diarreia/microbiologia , Enterocolite Pseudomembranosa/microbiologia , Adolescente , Adulto , Distribuição por Idade , Fatores Etários , Idoso , Criança , Pré-Escolar , Clostridium difficile/patogenicidade , Diarreia/induzido quimicamente , Diarreia/tratamento farmacológico , Diarreia/epidemiologia , Enterocolite Pseudomembranosa/induzido quimicamente , Enterocolite Pseudomembranosa/tratamento farmacológico , Enterocolite Pseudomembranosa/epidemiologia , Humanos , Incidência , Lactente , Pessoa de Meia-Idade , Recidiva , Fatores de Risco , Índice de Gravidade de Doença , Resultado do Tratamento , Adulto Jovem
17.
Gut Liver ; 10(2): 250-4, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26260753

RESUMO

BACKGROUND/AIMS: To determine the incidence and clinical characteristics of tuberculosis (TB) medication-associated Clostridium difficile infection. METHODS: This multicenter study included patients from eight tertiary hospitals enrolled from 2008 to 2013. A retrospective analysis was conducted to identify the clinical features of C. difficile infection in patients who received TB medication. RESULTS: C. difficile infection developed in 54 of the 19,080 patients prescribed TB medication, representing a total incidence of infection of 2.83 cases per 1,000 adults. Fifty-one of the 54 patients (94.4%) were treated with rifampin. The patients were usually treated with oral metronidazole, which produced improvement in 47 of the 54 patients (87%). Twenty-three patients clinically improved with continuous rifampin therapy for C. difficile infection. There were no significant differences in improvement between patients treated continuously (n=21) and patients in whom treatment was discontinued (n=26). CONCLUSIONS: The incidence of C. difficile infection after TB medication was not low considering the relatively low TB medication dosage compared to other antibiotics. It may not be always necessary to discontinue TB medication. Instead, decisions concerning discontinuation of TB medication should be based on TB status.


Assuntos
Antibióticos Antituberculose/efeitos adversos , Clostridium difficile , Enterocolite Pseudomembranosa/epidemiologia , Rifampina/efeitos adversos , Tuberculose/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anti-Infecciosos/uso terapêutico , Enterocolite Pseudomembranosa/induzido quimicamente , Enterocolite Pseudomembranosa/tratamento farmacológico , Feminino , Humanos , Incidência , Masculino , Metronidazol/uso terapêutico , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
18.
Pak J Pharm Sci ; 29(5 Suppl): 1805-1810, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28476706

RESUMO

Proper management of antibiotic-associated pseudo membranous colitis is not clear. This article is to investigate proper treatment of antibiotic-associated pseudo membranous colitis. Data of 67 patients (aged 18-69 years, with 31 males and 46 females) with antibiotic-associated pseudo membranous colitis were retrospectively analyzed including the demography, antibiotics to induce and for treatment of the pseudo membranous colitis, and other supportive measures. All 67 patients had a positive cytotoxin test, which confirmed the pseudo membranous colitis. Antibiotics which induced the pseudo membranous colitis included clindamycin, ofloxacin, piperacillin, cefatriaxone, penbritin and ceftazidime. Once the correct diagnosis was made, the culprit antibiotics were discontinued immediately, and narrow-spectrum antibiotics like metronidazole and vancomycin were administered in combination with correction of fluid and electrolyte abnormalities, use of vitamins C and B complex to repair the intestinal mucosa, and avoidance of antispasmodic and antidiarrheal agents. After appropriate treatment for 2-20 days, all patients recovered with no sequela. Sixty-two patients were clinically cured while five (7.5%) had diarrhea recurrence within two months of the end of therapy. Retreatment with tapering and extended period of metronidazole and/or vancomycin led to complete recovery of the patients. Multiple antibiotic agents are associated with pseudo membranous colitis, and correction of fluid and electrolyte abnormalities and use of vitamins to repair the intestinal mucosa should be performed to speed up the cure process.


Assuntos
Enterocolite Pseudomembranosa/induzido quimicamente , Enterocolite Pseudomembranosa/tratamento farmacológico , Adolescente , Adulto , Idoso , Clostridium difficile/isolamento & purificação , Enterocolite Pseudomembranosa/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
19.
Spec Care Dentist ; 35(6): 279-84, 2015 Nov-Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26297332

RESUMO

BACKGROUND: Gastrointestinal complications from antibiotic use, including Clostridium difficile infection (CDI), can have significant morbidity, especially among older patients. This descriptive study surveyed dentists to find out how they would respond to a patient with signs indicating potential CDI. METHODS: A survey on prescribing medications for older patients was mailed to 1,000 dentists in New Jersey. Questions were asked regarding antibiotic selection, probiotic use, and approach to a patient scenario of diarrhea after antibiotic use. RESULTS: Respondents chose amoxicillin most frequently as an antibiotic, and clindamycin if penicillin allergy. When informed their patients had diarrhea, 64.5% advised them to stop the antibiotic. If the patient continued to have diarrhea on follow-up, 75.5% contacted the patient's physician. Most (61.6%) do not prescribe probiotics prophylactically. CONCLUSIONS: Most dentists respond appropriately to antibiotic-associated diarrhea in advising to stop the antibiotic, and seeking physician involvement if no improvement, but there are still many who make recommendations that could delay appropriate care. Dentists may wish to learn more about benefits of probiotics.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/efeitos adversos , Assistência Odontológica para Idosos , Diarreia/induzido quimicamente , Diarreia/prevenção & controle , Enterocolite Pseudomembranosa/induzido quimicamente , Enterocolite Pseudomembranosa/prevenção & controle , Padrões de Prática Odontológica/estatística & dados numéricos , Idoso , Clostridium difficile , Tomada de Decisões , Diarreia/microbiologia , Enterocolite Pseudomembranosa/microbiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , New Jersey
20.
Gastroenterology ; 149(4): 883-5.e9, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26164495

RESUMO

We conducted an open-label crossover trial to test whether proton pump inhibitors (PPIs) affect the gastrointestinal microbiome to facilitate Clostridium difficile infection (CDI). Twelve healthy volunteers each donated 2 baseline fecal samples, 4 weeks apart (at weeks 0 and 4). They then took PPIs for 4 weeks (40 mg omeprazole, twice daily) and fecal samples were collected at week 8. Six individuals took the PPIs for an additional 4 weeks (from week 8 to 12) and fecal samples were collected from all subjects at week 12. Samples were analyzed by 16S ribosomal RNA gene sequencing. We found no significant within-individual difference in microbiome diversity when we compared changes during baseline vs changes on PPIs. There were, however, significant changes during PPI use in taxa associated with CDI (increased Enterococcaceae and Streptococcaceae, decreased Clostridiales) and taxa associated with gastrointestinal bacterial overgrowth (increased Micrococcaceae and Staphylococcaceae). In a functional analysis, there were no changes in bile acids on PPIs, but there was an increase in genes involved in bacterial invasion. These alterations could provide a mechanism by which PPIs predispose to CDI. ClinicalTrials.gov ID NCT01901276.


Assuntos
Bactérias/efeitos dos fármacos , Intestinos/efeitos dos fármacos , Microbiota , Omeprazol/administração & dosagem , Inibidores da Bomba de Prótons/administração & dosagem , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Clostridium difficile/efeitos dos fármacos , Clostridium difficile/isolamento & purificação , Estudos Cross-Over , Esquema de Medicação , Enterocolite Pseudomembranosa/induzido quimicamente , Enterocolite Pseudomembranosa/microbiologia , Fezes/microbiologia , Voluntários Saudáveis , Humanos , Intestinos/microbiologia , Omeprazol/efeitos adversos , Inibidores da Bomba de Prótons/efeitos adversos , Ribotipagem , Fatores de Risco , Fatores de Tempo
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