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1.
Ann Hematol ; 99(8): 1917-1924, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32556455

RESUMO

Febrile neutropenia (FN) is a common serious complication in patients undergoing hematopoietic stem cell transplantation (HSCT) requiring urgent evaluation and initiation of empiric broad spectrum antibiotics (BSA). The appropriate duration of BSA for FN in patients with negative cultures and no identifiable infection remains undefined. We retrospectively analyzed allogenic and autologous HSCT patients with FN and negative infectious work-up at our facility from 2012 to 2018. The early de-escalation group (EDG) included those who had BSA de-escalation to fluoroquinolone prophylaxis at least 24 h prior to absolute neutrophil count (ANC) recovery after the patient was fever-free for at least 48 h. Among 297 patients undergoing their first HSCT who experienced FN with negative infectious work-up, 83 patients were de-escalated early with the remaining 214 in the standard of care group (SCG) whose BSA were continued until ANC was > 500. Duration of broad-spectrum antibiotics was shorter in EDG compared to SCG (3.86 days vs. 4.62 days, p = 0.03). Rates of mortality, new infections, and clinical decompensation requiring intensive care unit transfer and/or pressor use within 30 days were all similar between the two groups (0% vs. 0.4% p = 1.00, 0% vs. 1.4% p = 0.56, 13.2% vs. 8.4% p = 0.27). This indicates that it is safe to de-escalate antibiotics prior to ANC recovery, leading to less BSA exposure.


Assuntos
Antibacterianos/administração & dosagem , Neutropenia Febril , Transplante de Células-Tronco Hematopoéticas , Infecções , Aloenxertos , Autoenxertos , Intervalo Livre de Doença , Neutropenia Febril/tratamento farmacológico , Neutropenia Febril/etiologia , Neutropenia Febril/mortalidade , Feminino , Humanos , Infecções/tratamento farmacológico , Infecções/etiologia , Infecções/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
2.
PLoS One ; 15(4): e0231798, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32302359

RESUMO

OBJECTIVE: To describe antibiotic prescription rates for Australian Aboriginal children aged <2 years living in three remote Northern Territory communities. DESIGN: A retrospective cohort study using electronic health records. SETTING: Three primary health care centres located in the Katherine East region. PARTICIPANTS: Consent was obtained from 149 mothers to extract data from 196 child records. There were 124 children born between January 2010 and July 2014 who resided in one of the three chosen communities and had electronic health records for their first two years of life. MAIN OUTCOME MEASURES: Antibiotic prescription rates, factors associated with antibiotic prescription and factors associated with appropriate antibiotic prescription. RESULTS: There were 5,675 Primary Health Care (PHC) encounters for 124 children (median 41, IQR 25.5, 64). Of the 5,675 PHC encounters, 1,542 (27%) recorded at least one infection (total 1,777) and 1,330 (23%) had at least one antibiotic prescription recorded (total 1,468). Children had a median five (IQR 2, 9) prescriptions in both their first and second year of life, with a prescription rate of 5.99/person year (95% CI 5.35, 6.63). Acute otitis media was the most common infection (683 records, 38%) and Amoxycillin was the most commonly prescribed antibiotic (797 prescriptions, 54%). Of the 1,468 recorded prescriptions, 398 (27%) had no infection recorded and 116 (8%) with an infection recorded were not aligned with local treatment guidelines. CONCLUSION: Prescription rates for Australian Aboriginal children in these communities are significantly higher than that reported nationally for non-Aboriginal Australians. Prescriptions predominantly aligned with treatment guidelines in this setting where there is a high burden of infectious disease.


Assuntos
Antibacterianos/uso terapêutico , Austrália , Peso ao Nascer , Criança , Feminino , Humanos , Incidência , Recém-Nascido , Infecções/tratamento farmacológico , Northern Territory , Grupo com Ancestrais Oceânicos , Razão de Chances , Gravidez , Prescrições , Atenção Primária à Saúde
3.
World Neurosurg ; 138: 242-245, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32179187

RESUMO

BACKGROUND: Complications of ventriculoperitoneal (VP) shunts include migration into various anatomic compartments and even extrusion through tissue layers. CASE DESCRIPTION: A 31-year-old female patient with a VP shunt presented with distal shunt tubing extruding through the skin at the level of the inguinal ligament. Shunt hardware was removed, and cultures grew Dermacoccus. The patient was treated with broad-spectrum antibiotics and underwent placement of a lumboperitoneal shunt. CONCLUSIONS: Dermacoccus is a gram-positive skin organism with rare human pathogenicity and not previously known to cause shunt infections.


Assuntos
Migração de Corpo Estranho/cirurgia , Infecções/tratamento farmacológico , Complicações Pós-Operatórias/terapia , Derivação Ventriculoperitoneal , Abdome , Adulto , Feminino , Migração de Corpo Estranho/microbiologia , Humanos , Infecções/etiologia
6.
Med. clín (Ed. impr.) ; 154(3): 101-107, feb. 2020. tab
Artigo em Espanhol | IBECS | ID: ibc-189063

RESUMO

En la última década se han experimentado grandes cambios en los tratamientos de los síndromes linfoproliferativos. A la quimioterapia convencional se suma ahora un amplio abanico de terapias dirigidas con diferentes indicaciones. El objetivo de esta revisión es evaluar el riesgo de infección asociado a estas terapias, así como tratar de establecer unas recomendaciones de prevención. En todos los casos, la enfermedad de base del paciente, así como los tratamientos concomitantes o los recibidos previamente, impactan en el riesgo de infección. Los anticuerpos anti-CD20 (rituximab, ofatumumab y obinutuzumab) se asocian a un mayor riesgo de infección bacteriana, vírica y de reactivación de infecciones latentes, así como a infecciones oportunistas. El alemtuzumab se asocia a inmunosupresión grave y mantenida. El ibrutinib y el acalabrutinib se asocian a infecciones bacterianas, especialmente respiratorias, infección fúngica invasiva e infecciones oportunistas. El idelalisib se asocia a un aumento de la incidencia de neumonía por Pneumocystis jirovecii y reactivación de citomegalovirus. El venetoclax se asocia a infecciones respiratorias y neutropenia. Los inhibidores de checkpoint inmune parecen no incrementar, por sí mismos, el riesgo de infección; sin embargo, el uso de glucocorticoides e inmunosupresores para controlar efectos adversos inmunorrelacionados sí conlleva un aumento del número de infecciones, incluyendo infecciones oportunistas. El brentuximab, la lenalidomida y los inhibidores de la histona deacetilasa no parecen asociarse a un mayor riesgo de infección. Aunque existe poca experiencia en el uso de terapias celulares, se ha observado un mayor número de infecciones en pacientes que han recibido más de 3 tratamientos antineoplásicos previamente, o en aquellos que han requerido tocilizumab o glucocorticoides para el manejo del síndrome de liberación de citocinas. En todos los pacientes se recomienda una actualización del calendario vacunal, cribado de infecciones latentes y profilaxis individualizada


Over the last decade, there have been important developments in the treatment of lymphoproliferative disorders. Apart from conventional chemotherapy, a wide array of therapies has been developed, with different indications. The aim of this review is to evaluate the risk of infection associated with these therapies, as well as establishing prevention recommendations. In all cases, the patient's underlying disease as well as concomitant or previous therapies have an impact on the risk of infection. Anti-CD20 antibodies (rituximab, ofatumumab and obinutuzumab) have been associated with a higher risk of bacterial and viral infection, as well as reactivation of latent infections and opportunistic infections. Alemtuzumab is associated with severe, protracted immunosuppression. Ibrutinib and acalabrutinib have been linked to bacterial infections (especially respiratory infections), invasive fungal infections and opportunistic infections. Idelalisib carries a higher risk of Pneumocystis jirovecii and infection and cytomegalovirus reactivation. Venetoclax is associated with respiratory infections and neutropenia. Immune checkpoint inhibitors are not directly associated with a higher risk of infection; nevertheless, the use of corticosteroids and immunosuppressants to control immune-related adverse events results in an increase of the risk of infection. Brentuximab, lenalidomide and histone deacetylase inhibitors do not seem to be associated with a higher risk of infections. Although data are scarce, a higher number of infections have been observed with cellular therapies, mostly in patients with more than 3 previous antineoplastic treatments or those receiving tocilizumab or corticosteroids for managing the cytokine release syndrome. In all patients, we recommend appropriate vaccination, screening for latent infections, and individualized prophylaxis recommendations


Assuntos
Humanos , Transtornos Linfoproliferativos/terapia , Infecções/complicações , Medição de Risco , Antígenos CD20/efeitos adversos , Infecções/tratamento farmacológico , Transtornos Linfoproliferativos/prevenção & controle , Antígenos CD20/administração & dosagem , Infecções Bacterianas , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Glucocorticoides/administração & dosagem , Imunossupressores , Fatores de Risco , Tirosina Quinase da Agamaglobulinemia/administração & dosagem
7.
Zhonghua Yu Fang Yi Xue Za Zhi ; 54(2): 187-191, 2020 Feb 06.
Artigo em Chinês | MEDLINE | ID: mdl-32074708

RESUMO

Objective: To investigate the drug resistance pattern and drug resistance genotypes of Salmonella. spp isolated from fecal specimens and anal swabs of diarrhea cases in Anhui Province. Methods: The 149 strains of Salmonella.spp isolated from feces and anal swabs of diarrhea cases in Anhui Province from April to October 2017 were selected. The serotypes of Salmonella.spp were identified by slide agglutination. The susceptibility of all strains to 14 antibiotics were determined by micro-broth dilution method. Sixty of the cephalosporin-resistant antibiotics were selected. The ß-lactamase encoding genes bla(TEM), bla(SHV), bla(OXA-1), bla(OXA-2), bla(PER), bla(CMY), bla(CTX-M), and colistin resistance genes mcr-1 and mcr-2 were performed using the multi-PCR method. Results: Of the 149 diarrhea cases, the median (P(25), P(75)) of the age was 5.0 (1.1, 38.5). The 92 of them were male and 54.4% were children. Of the 149 strains of Salmonella.spp, 105 strains had different degrees of resistance to 13 antibiotics other than imipenem. The resistance rate of ampicillin was 55.0% (82/149), which was the highest. 53.0% strains (79 strains) were multidrug resistant, main of which were Salmonella typhimurium and Salmonella enteritidis. A total of 53 resistance patterns were detected, and 10 strains were resistant to ampicillin-ampicillin/sulbactam-tetracycline-chloramphenicol-cefazolin-trimethoprim/sulfamethoxazole, which was the most common resistance pattern. Among the 60 cephalosporin resistant strains, 45 strains carried bla(TEM-1), 6 of which also carried bla(CTX-M-14) and 3 of which also carried bla(CTX-M-65). All the 32 strains carried only bla(TEM-1) show resistance to ampicillin and 31 of them show resistance to cefazolin. There were 2 strains showing negative results of gene detection. mcr-1 was detected in a multidrug resistant strain. Conclusion: The resistance of Salmonella.spp to ampicillin shows a serious situation in this region, and there were a number of multidrug resistant strains. The bla(TEM-1) was the major drug resistance gene detected in this research. Detection of the mcr-1 suggests the emergence of surveillance to colistin resistance of Salmonella.spp in this area.


Assuntos
Farmacorresistência Bacteriana/genética , Infecções/microbiologia , Salmonella/efeitos dos fármacos , Salmonella/genética , Adolescente , Adulto , Antibacterianos/farmacologia , Criança , Pré-Escolar , China , Feminino , Humanos , Lactente , Infecções/tratamento farmacológico , Masculino , Salmonella/isolamento & purificação , Adulto Jovem
8.
BMC Infect Dis ; 20(1): 102, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32013908

RESUMO

BACKGROUND: Minimising antimicrobial overuse is needed to limit antimicrobial resistance. There is little evidence on how often microbiological testing informs antimicrobial de-escalation (e.g. stopping, shortening duration, switching to narrower spectrum or intravenous to oral switch) at 48-72 h "review and revise". We performed a patient level analysis of diagnostic microbiology and antimicrobial prescribing to determine the impact of microbiology results on antimicrobial review outcomes. METHODS: Antimicrobial prescribing data were collected for hospitalised adults from across Brighton and Sussex University Hospitals NHS Trust using routine monthly audits of prescribing practice from July 2016 to April 2017. Microbiology testing data for cultures of blood, urine, sputum and cerebrospinal fluid (CSF) were gathered from the hospital pathology database and linked to prescriptions with matching patient identification codes. Antimicrobial prescriptions were grouped into "prescription episodes" (PEs), defined as one or more antimicrobials prescribed to the same patient for the same indication. Medical records were reviewed for all PEs with positive microbiology and a randomised sample of those with negative results to assess the impact of the microbiology result on the antimicrobial prescription(s). RESULTS: After excluding topical and prophylactic prescriptions, data were available for 382 inpatient antimicrobial prescriptions grouped into 276 prescription episodes. 162/276 (59%) had contemporaneous microbiology sent. After filtering likely contaminants, 33/276 (12%) returned relevant positive results, of which 20/33 (61%) had antimicrobials changed from empiric therapy as a result with 6/33 (18%) prompting de-escalation. Positive blood and CSF tended to have greater impact than urine or sputum cultures. 124/276 (45%) PEs returned only negative microbiology, and this was documented in the medical notes less often (9/40, 23%) than positive results (28/33, 85%). Out of 40 reviewed PEs with negative microbiology, we identified just one (~ 3%) in which antimicrobials were unambiguously de-escalated following the negative result. CONCLUSIONS: The majority of diagnostic microbiology tests sent to inform clinical management yielded negative results. However, negative microbiology contributed little to clinical decision making about antimicrobial de-escalation, perhaps reflecting a lack of trust in negative results by treating clinicians. Improving the negative predictive value of currently available diagnostic microbiology could help hospital prescribers in de-escalating antimicrobial therapy.


Assuntos
Anti-Infecciosos/uso terapêutico , Prescrições de Medicamentos/estatística & dados numéricos , Infecções/tratamento farmacológico , Técnicas Microbiológicas/estatística & dados numéricos , Adulto , Líquido Cefalorraquidiano/microbiologia , Prescrições de Medicamentos/normas , Inglaterra , Hospitalização/estatística & dados numéricos , Humanos , Infecções/microbiologia , Pessoa de Meia-Idade , Escarro/microbiologia , Urina/microbiologia
9.
s.l; RedARETS; feb. 2020.
Não convencional em Espanhol | LILACS, BRISA/RedTESA | ID: biblio-1095221

RESUMO

OBJETIVO: Se sugiere la utilización de gammaglobulinas endovenosa en infantes pretérmino (<1500gr con inmunodeficiencia) para profilaxis de infecciones graves. TECNOLOGÍA EVALUADA: Gammaglobulina endovenosa: La inmunoglobulina intravenosa (IGIV) contiene un conjunto inmunoglobulina G (IgG) extraída del plasma de más de 1000 donantes de sangre. La IGIV se administra con frecuencia a pacientes inmunodeficientes que tienen disminución de las capacidades de producción de anticuerpos. En pacientes inmunodeficientes se administra para mantener niveles adecuados de anticuerpos para prevenir infecciones y conferir inmunidad pasiva. MÉTODOS: Busqueda bibliográfica. Terminología: Medical Subject Headings (MeSH). Estrategia epistemonikos. Estrategia Cochrane library. RESUMEN DE LOS RESULTADOS: Inmunoglobulina intravenosa comparado con no tratamiento para prevenir infecciones en infantes de bajo peso o pretérmino. 15 de los estudios tuvieron alto riesgo de sesgo debido a fallas en el cegamiento, falta de grupo control, attrtion bias, report bias y no usar intención de tratar. La heterogeneidad I2 54% y 50%. Funnel plot asimétrico. Sólo un estudio pequeño bien diseñado con resultados negativos.


Assuntos
Humanos , Recém-Nascido , Lactente , gama-Globulinas/uso terapêutico , Recém-Nascido de Baixo Peso , Infecções/tratamento farmacológico , Avaliação da Tecnologia Biomédica , Análise Custo-Benefício
12.
Cochrane Database Syst Rev ; 1: CD001239, 2020 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-31995649

RESUMO

BACKGROUND: Neonates are at higher risk of infection due to immuno-incompetence. Maternal transport of immunoglobulins to the fetus mainly occurs after 32 weeks' gestation, and endogenous synthesis begins several months after birth. Administration of intravenous immunoglobulin (IVIG) provides immunoglobulin G (IgG) that can bind to cell surface receptors, provide opsonic activity, activate complement, promote antibody-dependent cytotoxicity and improve neutrophilic chemo-luminescence. Theoretically, infectious morbidity and mortality could be reduced by the administration of IVIG. OBJECTIVES: To assess the effects of IVIG on mortality and morbidity caused by suspected or proven infection at study entry in neonates. To assess in a subgroup analysis the effects of IgM-enriched IVIG on mortality from suspected infection. SEARCH METHODS: For this update, MEDLINE, EMBASE, The Cochrane Library, CINAHL, trial registries, Web of Science, reference lists of identified studies, meta-analyses and personal files were searched in 2013. No language restrictions were applied. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials involving newborn infants (< 28 days old); IVIG for treatment of suspected or proven bacterial or fungal infection compared with placebo or no intervention; and where one of the following outcomes was reported, mortality, length of hospital stay or psychomotor development at follow-up. DATA COLLECTION AND ANALYSIS: Statistical analyses included typical risk ratio (RR), risk difference (RD), weighted mean difference (WMD), number needed to treat for an additional beneficial outcome (NNTB) or an additional harmful outcome (NNTH), all with 95% confidence intervals (CIs), and the I2 statistic to examine for statistical heterogeneity. MAIN RESULTS: The updated search identified one published study that was previously ongoing. A total of 9 studies evaluating 3973 infants were included in this review. Mortality during hospital stay in infants with clinically suspected infection was not significantly different after IVIG treatment (9 studies (n = 2527); typical RR 0.95, 95% CI 0.80 to 1.13; typical RD -0.01, 95% CI - 0.04 to 0.02; I2 = 23% for RR and 29% for RD). Death or major disability at 2 years corrected age was not significantly different in infants with suspected infection after IVIG treatment (1 study (n = 1985); RR 0.98, 95% CI 0.88 to 1.09; RD -0.01, 95% CI -0.05 to 0.03). Mortality during hospital stay was not significantly different after IVIG treatment in infants with proven infection at trial entry (1 trial (n = 1446); RR 0.95, 95% CI 0.74 to 1.21; RD -0.01, 95% CI -0.04 to 0.03). Death or major disability at 2 years corrected age was not significantly different after IVIG treatment in infants with proven infection at trial entry (1 trial (n = 1393); RR 1.03, 95% CI 0.91 to 1.18; RD 0.01, 95% CI -0.04 to 0.06). Mortality during hospital stay in infants with clinically suspected or proven infection at trial entry was not significantly different after IVIG treatment (1 study (n = 3493); RR 1.00, 95% CI 0.86 to 1.16; RD 0.00, 95% CI - 0.02 to 0.03). Death or major disability at 2 years corrected age was not significantly different after IVIG treatment in infants with suspected or proven infection at trial entry (1 study (n = 3493); RR 1.00, 95% CI 0.92 to 1.09; RD -0.00, 95% CI -0.03 to 0.03). Length of hospital stay was not reduced for infants with suspected or proven infection at trial entry (1 study (n = 3493); mean difference (MD) 0.00 days, 95% CI -0.61 to 0.61). No significant difference in mortality during hospital stay after administration of IgM-enriched IVIG for suspected infection at trial entry was reported in 4 studies (n = 266) (typical RR 0.68, 95% CI 0.39 to 1.20; RD -0.06, 95% CI -0.14 to 0.02; I2 = 17% for RR and 53% for RD). AUTHORS' CONCLUSIONS: The undisputable results of the INIS trial, which enrolled 3493 infants, and our meta-analyses (n = 3973) showed no reduction in mortality during hospital stay, or death or major disability at two years of age in infants with suspected or proven infection. Although based on a small sample size (n = 266), this update provides additional evidence that IgM-enriched IVIG does not significantly reduce mortality during hospital stay in infants with suspected infection. Routine administration of IVIG or IgM-enriched IVIG to prevent mortality in infants with suspected or proven neonatal infection is not recommended. No further research is recommended.


Assuntos
Imunoglobulinas Intravenosas/uso terapêutico , Infecções/tratamento farmacológico , Humanos , Recém-Nascido de Baixo Peso , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/prevenção & controle , Infecções/mortalidade , Tempo de Internação , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
14.
Int J Infect Dis ; 92: 151-159, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31935538

RESUMO

BACKGROUND: Vancomycin is a common drug used in children with severe infection. In adults, at least 15 mg/L of the optimal vancomycin trough concentration (Ctrough) is needed to generate the target 24-h area under the concentration-time curve (AUC24) to the minimum inhibitory concentration (MIC) of 400 for a pathogen with the MIC ≤1 mg/L. OBJECTIVES: To determine vancomycin PK in children with severe infection and to explore the correlation between vancomycin Ctrough and AUC24 in children, as well as to propose the appropriate vancomycin dosages using Monte Carlo simulation. MATERIALS AND METHODS: Children aged 2-18 years who were admitted to Chiang Mai University Hospital and received intravenous vancomycin for severe infection were included in the study. Serum samples for vancomycin PK were obtained before and serially after the administration of the first dose according to the protocol. Pharmacokinetic analyses were performed using Phoenix WinNonlin® 7.0 and NLME™7.0. RESULTS: Fourteen children with 64% males and age range from 2 to 13 years were included in this study. Non-compartmental analysis revealed the median volume of distribution, clearance, and elimination half-life of 0.58 L/kg, 2.82 mL/kg/min and 2.33 h, respectively. Vancomycin serum concentrations were best described by a two-compartmental model with first-order elimination.The observed Ctrough at 6 h correlated well with the AUC24. The median vancomycin Ctrough at steady state that correlated with the AUC24 ≥ 400 and <800 were 11.18, 9.50, 7.91 and 6.55 mg/L in simulated children receiving vancomycin 40, 60, 80 and 100 mg/kg/day, respectively. CONCLUSION: Correlation between vancomycin Ctrough and AUC24 values in children has been observed. However, the values of Ctrough that correlate with the target AUC24≥400 in children are lower than the values observed and targeted in adults.


Assuntos
Antibacterianos/farmacocinética , Infecções/tratamento farmacológico , Vancomicina/farmacocinética , Administração Intravenosa , Adolescente , Antibacterianos/uso terapêutico , Área Sob a Curva , Criança , Pré-Escolar , Feminino , Hospitais Universitários , Humanos , Infecções/metabolismo , Masculino , Testes de Sensibilidade Microbiana , Método de Monte Carlo , Vancomicina/administração & dosagem , Vancomicina/uso terapêutico
16.
Am J Hosp Palliat Care ; 37(1): 27-33, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31185722

RESUMO

BACKGROUND: Antibiotic use may increase hospital length of stay (LOS) among older patients with advanced cancer who are transitioned to comfort measures. METHODS: We studied a cohort of patients with advanced cancer aged ≥65 years who were transitioned to comfort measures during admission from July 1, 2014, through November 30, 2016. We evaluated the association between antibiotic exposure and LOS using a Poisson regression model adjusted for age, gender, cancer type, comorbidities, infection, and intensive care unit admission. RESULTS: Among 461 patients with advanced cancer, median age was 74 years (range: 65-99), 49.0% (n = 226) were female, and 20.6% (n = 95) had liquid tumors. Overall, 82.9% (n = 382) received ≥1 antibiotic and 64.6% (n = 298) had ≥1 infection diagnosis during hospitalization. Infection diagnoses commonly included sepsis (35%, n = 161/461), pneumonia (25%, n = 117/461), and urinary tract infection (14%, n = 66/461). Among those receiving antibiotics, the most common choices included vancomycin (79%, n = 300/382), cephalosporins (63%, n = 241/382), and penicillins (45%, n = 172/382). In a multivariable Poisson regression model, LOS was 34% longer (count ratio = 1.34, [95% confidence interval: 1.20-1.51]) among those exposed versus unexposed to antibiotics. CONCLUSIONS: Antibiotic use among patients with advanced cancer who are transitioned to comfort measures is associated with longer LOS. These data illustrate the importance of tradeoffs associated with antibiotic use, such as unintended increased LOS, when striving for goal-concordant care near the end of life.


Assuntos
Antibacterianos/uso terapêutico , Infecções/tratamento farmacológico , Infecções/epidemiologia , Neoplasias/epidemiologia , Neoplasias/patologia , Conforto do Paciente/organização & administração , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/administração & dosagem , Comorbidade , Grupos de Populações Continentais , Feminino , Humanos , Infecções/microbiologia , Tempo de Internação , Masculino , Fatores Sexuais , Assistência Terminal/organização & administração , Fatores de Tempo
17.
PLoS Med ; 16(12): e1002984, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31821329

RESUMO

BACKGROUND: Infection is an important, preventable cause of maternal morbidity, and pregnancy-related sepsis accounts for 11% of maternal deaths. However, frequency of maternal infection is poorly described, and, to our knowledge, it remains the one major cause of maternal mortality without a systematic review of incidence. Our objective was to estimate the average global incidence of maternal peripartum infection. METHODS AND FINDINGS: We searched Medline, EMBASE, Global Health, and five other databases from January 2005 to June 2016 (PROSPERO: CRD42017074591). Specific outcomes comprised chorioamnionitis in labour, puerperal endometritis, wound infection following cesarean section or perineal trauma, and sepsis occurring from onset of labour until 42 days postpartum. We assessed studies irrespective of language or study design. We excluded conference abstracts, studies of high-risk women, and data collected before 1990. Three reviewers independently selected studies, extracted data, and appraised quality. Quality criteria for incidence/prevalence studies were adapted from the Joanna Briggs Institute. We used random-effects models to obtain weighted pooled estimates of incidence risk for each outcome and metaregression to identify study-level characteristics affecting incidence. From 31,528 potentially relevant articles, we included 111 studies of infection in women in labour or postpartum from 46 countries. Four studies were randomised controlled trials, two were before-after intervention studies, and the remainder were observational cohort or cross-sectional studies. The pooled incidence in high-quality studies was 3.9% (95% Confidence Interval [CI] 1.8%-6.8%) for chorioamnionitis, 1.6% (95% CI 0.9%-2.5%) for endometritis, 1.2% (95% CI 1.0%-1.5%) for wound infection, 0.05% (95% CI 0.03%-0.07%) for sepsis, and 1.1% (95% CI 0.3%-2.4%) for maternal peripartum infection. 19% of studies met all quality criteria. There were few data from developing countries and marked heterogeneity in study designs and infection definitions, limiting the interpretation of these estimates as measures of global infection incidence. A limitation of this review is the inclusion of studies that were facility-based or restricted to low-risk groups of women. CONCLUSIONS: In this study, we observed pooled infection estimates of almost 4% in labour and between 1%-2% of each infection outcome postpartum. This indicates maternal peripartum infection is an important complication of childbirth and that preventive efforts should be increased in light of antimicrobial resistance. Incidence risk appears lower than modelled global estimates, although differences in definitions limit comparability. Better-quality research, using standard definitions, is required to improve comparability between study settings and to demonstrate the influence of risk factors and protective interventions.


Assuntos
Antibacterianos/uso terapêutico , Cesárea/estatística & dados numéricos , Infecções/epidemiologia , Sepse/tratamento farmacológico , Estudos Transversais , Parto Obstétrico , Feminino , Humanos , Infecções/tratamento farmacológico , Trabalho de Parto/imunologia , Parto/imunologia , Período Periparto , Período Pós-Parto , Gravidez
18.
BMC Health Serv Res ; 19(1): 942, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31805940

RESUMO

BACKGROUND: Antimicrobial resistance (AMR) is a prominent threat to public health. Although many guidelines have been developed over the years to tackle this issue, their impact on health care practice varies. Guidelines are often based on evidence from clinical trials, but these have limitations, particularly in the breadth and generalisability of the evidence and evaluation of the guidelines' uptake. The aim of this study was to investigate how national and local guidelines for managing common infections are developed and explore guideline committee members' opinions about using real-world observational evidence in the guideline development process. METHODS: Six semi-structured interviews were completed with participants who had contributed to the development or adjustment of national or local guidelines on antimicrobial prescribing over the past 5 years (from the English National Institute for Health and Care Excellence (NICE)). Interviews were audio recorded and transcribed verbatim. Data was analysed thematically. This also included review of policy documents including guidelines, reports and minutes of guideline development group meetings that were available to the public. RESULTS: Three key themes emerged through our analysis: perception versus actual guideline development process, using other types of evidence in the guideline development process, and guidelines are not enough to change antibiotic prescribing behaviour. In addition, our study was able to provide some insight between the documented and actual guideline development process within NICE, as well as how local guidelines are developed, including differences in types of evidence used. CONCLUSIONS: This case study indicates that there is the potential for a wider range of evidence to be included as part of the guideline development process at both the national and local levels. There was a general agreement that the inclusion of observational data would be appropriate in enhancing the guideline development process, as well providing a potential solution for monitoring guideline use in clinical practice, and improving the implementation of treatment guidelines in primary care.


Assuntos
Antibacterianos/uso terapêutico , Infecções/tratamento farmacológico , Guias de Prática Clínica como Assunto , Atenção Primária à Saúde , Medicina Baseada em Evidências , Humanos , Estudos Observacionais como Assunto
20.
Pharmacol Res Perspect ; 7(6): e00535, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31859459

RESUMO

Monoclonal antibodies (mAbs) have emerged as a major class of therapeutic agents on the market. To date, approximately 80 mAbs have been granted marketing approval. In 2018, 12 new mAbs were approved by the FDA, representing 20% of the total number of approved drugs. The majority of mAb therapeutics are for oncological and immunological/infectious diseases, but these are expanding into other disease areas. Over 100 monoclonal antibodies are in development, and their unique features ensure that these will remain a part of the therapeutic pipeline. Thus, the therapeutic value and the elucidation of their pharmacological properties supporting clinical development of these large molecules are unquestioned. However, their utilization as pharmacological tools in academic laboratories has lagged behind their small molecule counterparts. Early therapeutic mAbs targeted soluble cytokines, but now that mAbs also target membrane-bound receptors and have increased circulating half-life, their pharmacology is more complex. The principles of pharmacology have enabled the development of high affinity, potent and selective small molecule therapeutics with reduced off-target effects and drug-drug interactions. This review will discuss how the same basic principles can be applied to mAbs, with some important differences. Monoclonal antibodies have several benefits, such as fewer off-target adverse effects, fewer drug-drug interactions, higher specificity, and potentially increased efficacy through targeted therapy. Modifications to decrease the immunogenicity and increase the efficacy are described, with examples of optimizing their pharmacokinetic properties and enabling oral bioavailability. Increased awareness of these advances may help to increase their use in exploratory research and further understand and characterize their pharmacological properties.


Assuntos
Anticorpos Monoclonais/farmacologia , Doenças do Sistema Imunitário/tratamento farmacológico , Infecções/tratamento farmacológico , Neoplasias/tratamento farmacológico , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/uso terapêutico , Disponibilidade Biológica , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Humanos , Doenças do Sistema Imunitário/imunologia , Infecções/imunologia , Terapia de Alvo Molecular/métodos , Neoplasias/imunologia , Relação Estrutura-Atividade , Distribuição Tecidual , Resultado do Tratamento
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