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BACKGROUND: Ileal pouch anal anastomosis (IPAA) circumferential pouch advancement (CPA) involves full-thickness transanal 180-360° dissection of the distal pouch, allowing the advancement of healthy bowel to cover the internal opening of a vaginal fistula. We aimed to describe the long-term outcomes of this rare procedure. METHODS: Patients with IPAA who underwent transanal pouch advancement for any indication between 2009 and 2021 were included. Demographics, operative details, and outcomes were reviewed. An early fistula was defined as occurring within 1 year of IPAA construction. Clinical success was defined as resolution of symptoms necessitating CPA, pouch retention, and no stoma at the time of follow-up. Figures represent the median (interquartile range) or frequency (%). RESULTS: Over a 12-year period, nine patients were identified; the median age at CPA was 41 (36-44) years. Four patients developed early fistula after index IPAA, and five developed late fistulae. The median number of fistula repair procedures prior to CPA was 2 (1-2). All patients were diagnosed with ulcerative colitis at the time of IPAA and all late patients were re-diagnosed with Crohn's disease. Four (44.4%) patients had ileostomies present at the time of surgery, three (33.3%) had one constructed during surgery, and two (22.2%) never had a stoma. The median follow-up time was 11 (6-24) months. Clinical success was achieved in four of the nine (44.4%) patients at the time of the last follow-up. CONCLUSIONS: Transanal circumferential pouch advancement was an effective treatment for refractory pouch vaginal fistulas and may be offered to patients who have had previous attempts at repair.
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Colite Ulcerativa , Bolsas Cólicas , Complicações Pós-Operatórias , Proctocolectomia Restauradora , Fístula Vaginal , Humanos , Feminino , Adulto , Bolsas Cólicas/efeitos adversos , Fístula Vaginal/cirurgia , Fístula Vaginal/etiologia , Proctocolectomia Restauradora/efeitos adversos , Proctocolectomia Restauradora/métodos , Resultado do Tratamento , Colite Ulcerativa/cirurgia , Estudos Retrospectivos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Doença de Crohn/cirurgia , Doença de Crohn/complicações , SeguimentosRESUMO
BACKGROUND: Ileoanal pouch is a demanding procedure with many potential technical complications including bladder or ureteral injury, while inflammation or stricture of the anastomosis or anal transition zone may lead to the formation of strictures and fistulae, including to the adjacent urethra. Pouch urinary tract fistulae are rare. We aimed to describe the presentation, diagnostic workup, and management of patients with pouch urinary at our center. METHODS: Our prospectively maintained pouch registry was queried using diagnostic codes and natural language processing free-text searches to identify ileoanal pouch patients diagnosed with any pouch-urinary tract fistula from 1997 to 2022. Descriptive statistics and pouch survival using Kaplan-Meier curves are presented. Numbers represent frequency (proportion) or median (range). RESULTS: Over 25 years, urinary fistulae were observed 27 pouch patients; of these, 16 of the index pouches were performed at our institution [rate 0.3% (16/5236)]. Overall median age was 42 (27-62) years, and 92.3% of the patients were male. Fistula locations included pouch-urethra in 13 patients (48.1%), pouch-bladder in 12 patients (44.4%), and anal-urethra in 2 (7.4%). The median time from pouch to fistula was 7.0 (0.3-38) years. Pouch excision and end ileostomy were performed in 12 patients (bladder fistula, n = 3; urethral fistula, n = 9), while redo ileal pouch-anal anastomosis (IPAA) was performed in 5 patients (bladder fistula, n = 3; urethral fistula, n = 2). The 5-year overall pouch survival after fistula to the bladder was 58.3% vs. 33.3% with urethral fistulae (p = 0.25). CONCLUSION: Pouch-urinary tract fistulae are a rare, morbid, and difficult to treat complication of ileoanal pouch that requires a multidisciplinary, often staged, surgical approach. In the long term, pouches with bladder fistulae were more likely to be salvaged than pouches with urethral fistulae.
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Bolsas Cólicas , Complicações Pós-Operatórias , Fístula Urinária , Humanos , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Bolsas Cólicas/efeitos adversos , Fístula Urinária/etiologia , Fístula Urinária/cirurgia , Complicações Pós-Operatórias/etiologia , Fatores de Tempo , Sistema de Registros , Estudos Prospectivos , Proctocolectomia Restauradora/efeitos adversos , Fístula da Bexiga Urinária/etiologia , Fístula da Bexiga Urinária/cirurgia , Estimativa de Kaplan-MeierRESUMO
PURPOSE: The safety of early ileostomy reversal after ileal pouch anal anastomosis (IPAA) has not been established. Our hypothesis was that ileostomy reversal before 8 weeks is associated with negative outcomes. METHODS: This was a retrospective cohort study from a prospectively maintained institutional database. Patients who underwent primary IPAA with ileostomy reversal between 2000 and 2021 from a Pouch Registry were stratified on the basis of timing of reversal. Those reversed before 8 weeks (early) and those reversed from 8 weeks to 116 days (routine) were compared. The primary outcome was overall complications according to timing and reason for closure. RESULTS: Ileostomy reversal was performed early in 92 patients and routinely in 1908. Median time to closure was 49 days in the early group and 93 days in the routine group. Reasons for early reversal were stoma-related morbidity in 43.3% (n = 39) and scheduled closure in 56.7% (n = 51). The complication rate in the early group was 17.4% versus 11% in the routine group (p = 0.085). When early patients were stratified according to reason for reversal, those reversed early for stoma-related morbidity had an increased complication rate compared to the routine group (25.6% vs. 11%, p = 0.006). Patients undergoing scheduled reversal in the early group did not have increased complications (11.8% vs. 11%, p = 0.9). There was a higher likelihood of pouch anastomotic leak when reversal was performed early for stoma complications compared to routinely (OR 5.13, 95% CI 1.01-16.57, p = 0.049). CONCLUSIONS: Early closure is safe but could be delayed in stoma morbidity as patients may experience increased complications.
Assuntos
Colite Ulcerativa , Bolsas Cólicas , Proctocolectomia Restauradora , Humanos , Proctocolectomia Restauradora/efeitos adversos , Ileostomia/efeitos adversos , Estudos Retrospectivos , Fístula Anastomótica/etiologia , Fístula Anastomótica/cirurgia , Anastomose Cirúrgica/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Colite Ulcerativa/cirurgia , Bolsas Cólicas/efeitos adversosRESUMO
Background: Despite a high burden of disease that requires critical care services, there are a limited number of intensivists in South Africa (SA). Medical practitioners at district and regional public sector hospitals frequently manage critically ill patients in the absence of intensivists, despite these medical practitioners having had minimal exposure to critical care during their undergraduate training. Objectives: To identify core competencies in critical care for medical practitioners who provide critical care services at public sector hospitals in SA where intensivists are not available to direct patient management. Methods: A preliminary list of core competencies in critical care was compiled. Thereafter, 13 national and international experts were requested to achieve consensus on a final list of core competencies that are required for critical care by medical practitioners, using a modified Delphi process. Results: A final list of 153 core competencies in critical care was identified. Conclusion: The core competencies identified by this study could assist in developing training programmes for medical practitioners to improve the quality of critical care services provided at district and regional hospitals in SA. Contribution of the study: The study provides consensus on a list of core competencies in critical care that non-intensivist medical practitioners managing critically ill patients in healthcare settings in South Africa, especially where intensivists are not readily available, should have. The list can form the core content of training programmes aimed at improving critical care competence of general medical practitioners, and in this way hopefully improve the overall outcomes of critically ill patients in South Africa.
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Ceftriaxone is a broad-spectrum cephalosporin that may be one option to treat methicillin-susceptible Staphylococcus aureus (MSSA). Although MSSA may be susceptible to ceftriaxone, the minimum inhibitory concentration (MIC) is generally two- to four-fold higher than other susceptible bacterial pathogens. This study aimed to explore the pharmacodynamics of ceftriaxone against MSSA and to determine the likely optimal dose. A hollow-fibre infection model was used with one clinical MSSA isolate (MIC = 4 mg/L) at an initial inoculum of 1 × 106 CFU/mL. Ceftriaxone dosing regimens of 1 g once and twice daily and 2 g once and twice daily were simulated. Ceftriaxone 1 g dosing regimens did not substantially impact bacterial killing within the first 12 h. Conversely, when administered as a 2 g dose either once or twice daily, an approximate 1-log10 bacterial reduction was observed where it plateaued for up to 96 h. No resistance was identified. Only a high ceftriaxone dose of 2 g twice daily achieves bacterial killing and sustained inhibition of bacterial growth. Ceftriaxone at routinely used doses is unsuitable for the treatment of MSSA infections and alternative agents should be preferentially used.
Assuntos
Infecções Estafilocócicas , Staphylococcus aureus , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Ceftriaxona/farmacologia , Ceftriaxona/uso terapêutico , Humanos , Meticilina/farmacologia , Testes de Sensibilidade Microbiana , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologiaRESUMO
BACKGROUND: Most intensive care unit (ICU) patients receive broad-spectrum antibiotics. While lifesaving in some, in others these treatments may be unnecessary and place patients at risk of antibiotic-associated harms. OBJECTIVES: To review the literature exploring how we diagnose infection in patients in the ICU and address the safety and utility of a 'watchful waiting' approach to antibiotic initiation with selected patients in the ICU. SOURCES: A semi-structured search of PubMed and Cochrane Library databases for articles published in English during the past 15 years was conducted. CONTENT: Distinguishing infection from non-infectious mimics in ICU patients is uniquely challenging. At present, we do not have access to a rapid point-of-care test that reliably differentiates between individuals who need antibiotics and those who do not. A small number of studies have attempted to compare early aggressive versus conservative antimicrobial strategies in the ICU. However, this body of literature is small and not robust enough to guide practice. IMPLICATIONS: This issue will not likely be resolved until there are diagnostic tests that rapidly and reliably identify the presence or absence of infection in the ICU population. In the meantime, prospective trials that identify clinical situations wherein it is safe to delay or withhold antibiotic initiation in the ICU until the presence of an infection is proven are warranted.
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Antibacterianos/administração & dosagem , Cuidados Críticos/normas , Unidades de Terapia Intensiva , Uso Excessivo de Medicamentos Prescritos/prevenção & controle , Cuidados Críticos/métodos , Humanos , Estudos Observacionais como Assunto , Guias de Prática Clínica como Assunto , Uso Excessivo de Medicamentos Prescritos/estatística & dados numéricos , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Sepse/tratamento farmacológico , Conduta ExpectanteRESUMO
The study aimed to evaluate saturation of piperacillin elimination in critically ill adult patients. Seventeen critically ill adult patients received continuous and intermittent infusion of piperacillin/tazobactam. Piperacillin plasma concentrations (nâ¯=â¯217) were analysed using population pharmacokinetic (PopPK) modelling. Post-hoc simulations were performed to evaluate the type I error rate associated with the study. Unseen data were used to validate the final model. The mean error (ME) and root mean square error (RMSE) were calculated as a measure of bias and imprecision, respectively. A PopPK model with parallel linear and non-linear elimination best fitted the data. The median and 95% confidence interval (CI) for the model parameters drug clearance (CL), volume of central compartment (V), volume of peripheral compartment (Vp) and intercompartmental clearance (Q) were 9 (7.69-11) L/h, 6.18 (4.93-11.2) L, 11.17 (7.26-12) L and 15.61 (12.66-23.8) L/h, respectively. The Michaelis-Menten constant (Km) and the maximum elimination rate for Michaelis-Menten elimination (Vmax) were estimated without population variability in the model to avoid overfitting and inflation of the type I error rate. The population estimates for Km and Vmax were 37.09 mg/L and 353.57 mg/h, respectively. The bias (ME) was -20.8 (95% CI -26.2 to -15.4) mg/L, whilst imprecision (RMSE) was 49.2 (95% CI 41.2-56) mg/L. In conclusion, piperacillin elimination is (partially) saturable. Moreover, the population estimate for Km lies within the therapeutic window and therefore saturation of elimination should be accounted for when defining optimum dosing regimens for piperacillin in critically ill patients.
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Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Piperacilina/administração & dosagem , Piperacilina/farmacocinética , Idoso , Antibacterianos/sangue , Antibacterianos/uso terapêutico , Área Sob a Curva , Simulação por Computador , Estado Terminal , Esquema de Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Piperacilina/sangue , Piperacilina/uso terapêuticoRESUMO
AIMS: Custom flange acetabular components (CFACs) are a patient-specific option for addressing large acetabular defects at revision total hip arthroplasty (THA), but patient and implant characteristics that affect survivorship remain unknown. This study aimed to identify patient and design factors related to survivorship. PATIENTS AND METHODS: A retrospective review of 91 patients who underwent revision THA using 96 CFACs was undertaken, comparing features between radiologically failed and successful cases. Patient characteristics (demographic, clinical, and radiological) and implant features (design characteristics and intraoperative features) were collected. There were 74 women and 22 men; their mean age was 62 years (31 to 85). The mean follow-up was 24.9 months (sd 27.6; 0 to 116). Two sets of statistical analyses were performed: 1) univariate analyses (Pearson's chi-squared and independent-samples Student's t-tests) for each feature; and 2) bivariable logistic regressions using features identified from a random forest analysis. RESULTS: Radiological failure and revision rates were 23% and 12.5%, respectively. Revisions were undertaken at a mean of 25.1 months (sd 26.4) postoperatively. Patients with radiological failure were younger at the time of the initial procedure, were less likely to have a diagnosis of primary osteoarthritis (OA), were more likely to have had ischial screws in previous surgery, had fewer ischial screw holes in their CFAC design, and had more proximal ischial fixation. Random forest analysis identified the age of the patient and the number of locking and non-locking screws used for inclusion in subsequent bivariable logistic regression, but only age (odds ratio 0.93 per year) was found to be significant. CONCLUSION: We identified both patient and design features predictive of CFAC survivorship. We found a higher rate of failure in younger patients, those whose primary diagnosis was not OA, and those with more proximal ischial fixation or fewer ischial fixation options. Cite this article: Bone Joint J 2019;101-B(6 Supple B):68-76.
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Acetábulo/cirurgia , Artroplastia de Quadril/métodos , Acetábulo/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Artroplastia de Quadril/instrumentação , Parafusos Ósseos , Feminino , Prótese de Quadril , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Quadril/diagnóstico por imagem , Osteoartrite do Quadril/cirurgia , Desenho de Prótese , Falha de Prótese , Reoperação/estatística & dados numéricos , Estudos Retrospectivos , Tomografia Computadorizada por Raios XRESUMO
Vancomycin is a commonly used antibiotic due to the high burden of methicillin-resistant Staphylococcus aureus infections. This study aimed to describe the pharmacokinetics (PK) of vancomycin in Australian Indigenous patients with severe sepsis, and advise an optimal dosing strategy. A population PK study was conducted in a remote Australian intensive care unit (ICU). Serial plasma samples were collected over one to two dosing intervals and assayed by validated chromatography. Concentration-time data collected were analysed using Pmetrics® software. The final population PK model was then used for Monte Carlo dosing simulations to determine optimal loading and intermittent maintenance doses. Fifteen Indigenous subjects were included for analysis with a median (interquartile range, IQR) age, weight and creatinine clearance (CrCL) of 43 (34-46) years, 73 (66-104) kg and 99 (56-139) ml/minute respectively. A two-compartment model described the data adequately. Vancomycin clearance (CL) and volume of distribution of the central compartment (Vc) were described by CrCL and patient weight respectively. Median (IQR) CL, Vc, distribution rate constants from central to peripheral, and from peripheral to central compartments were 4.6 (3.8-5.6) litres per hour, 25.4 (16.1-31.3) litres, 0.46 (0.28-0.52)/hour and 0.25 (0.12-0.37)/hour respectively. No significant interethnic PK differences were observed in comparison to published data. Therapeutic loading doses were significantly dependent on both weight and CrCL, whereas maintenance doses were dependent on CrCL. In the absence of severe renal impairment, initiation of maintenance dose eight hours post-loading dose achieved higher probability of target attainment at 24 hours. This is the first report of vancomycin PK in this patient group.
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Antibacterianos/administração & dosagem , Estado Terminal , Sepse/tratamento farmacológico , Vancomicina/administração & dosagem , Adulto , Antibacterianos/farmacocinética , Feminino , Humanos , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade , Método de Monte Carlo , Grupos Populacionais , Estudos Prospectivos , Vancomicina/farmacocinéticaRESUMO
Unnecessary pathology tests performed in intensive care units (ICU) might lead to increased costs of care and potential patient harm due to unnecessary phlebotomy. We hypothesised that a multimodal intervention program could result in a safe and effective reduction in the pathology tests ordered in our ICU. We conducted a single-centre pre- and post-study using multimodal interventions to address commonly ordered routine tests. The study was performed during the same six month period (August to February) over three years: 2012 to 2013 (pre-intervention), 2013 to 2014 (intervention) and 2014 to 2015 (post-intervention). Interventions consisted of staff education, designing new pathology forms, consultant-led pathology test ordering and intensive monitoring for a six-month period. The results of the study showed that there was a net savings of over A$213,000 in the intervention period and A$175,000 in the post-intervention period compared to the pre-intervention period. There was a 28% reduction in the tests performed in the intervention period (P <0.0001 compared to pre-intervention period) and 26% in the post-intervention period (P <0.0001 compared to pre-intervention period). There were no ICU or hospital mortality differences between the groups. There were no significant haemoglobin differences between the groups. A multimodal intervention safely reduced pathology test ordering in the ICU, resulting in substantial cost savings.
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Cuidados Críticos/métodos , Testes Diagnósticos de Rotina/estatística & dados numéricos , Testes Hematológicos/estatística & dados numéricos , Melhoria de Qualidade/estatística & dados numéricos , Cuidados Críticos/economia , Testes Diagnósticos de Rotina/economia , Testes Hematológicos/economia , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , QueenslandRESUMO
The scourge of antibiotic resistance threatens modern healthcare delivery. A contributing factor to this significant issue may be antibiotic dosing, whereby standard antibiotic regimens are unable to suppress the emergence of antibiotic resistance. This article aims to review the role of pharmacokinetic and pharmacodynamic (PK/PD) measures for optimising antibiotic therapy to minimise resistance emergence. It also seeks to describe the utility of combination antibiotic therapy for suppression of resistance and summarise the role of biomarkers in individualising antibiotic therapy. Scientific journals indexed in PubMed and Web of Science were searched to identify relevant articles and summarise existing evidence. Studies suggest that optimising antibiotic dosing to attain defined PK/PD ratios may limit the emergence of resistance. A maximum aminoglycoside concentration to minimum inhibitory concentration (MIC) ratio of > 20, a fluoroquinolone area under the concentration-time curve to MIC ratio of > 285 and a ß-lactam trough concentration of > 6 × MIC are likely required for resistance suppression. In vitro studies demonstrate a clear advantage for some antibiotic combinations. However, clinical evidence is limited, suggesting that the use of combination regimens should be assessed on an individual patient basis. Biomarkers, such as procalcitonin, may help to individualise and reduce the duration of antibiotic treatment, which may minimise antibiotic resistance emergence during therapy. Future studies should translate laboratory-based studies into clinical trials and validate the appropriate clinical PK/PD predictors required for resistance suppression in vivo. Other adjunct strategies, such as biomarker-guided therapy or the use of antibiotic combinations require further investigation.
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Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Medicina de Precisão/métodos , Aminoglicosídeos/farmacocinética , Aminoglicosídeos/uso terapêutico , Antibacterianos/farmacocinética , Biomarcadores/metabolismo , Quimioterapia Combinada , Fluoroquinolonas/farmacocinética , Fluoroquinolonas/uso terapêutico , Humanos , Testes de Sensibilidade Microbiana/métodos , Terapia de Alvo Molecular , Pró-Calcitonina/metabolismoRESUMO
Augmented renal clearance (ARC) refers to the enhanced renal excretion of circulating solute commonly demonstrated in numerous critically ill subgroups. This study aimed to describe the prevalence of ARC in critically ill Indigenous Australian patients and explore the accuracy of commonly employed mathematical estimates of glomerular filtration. We completed a single-centre, prospective, observational study in the intensive care unit (ICU), Alice Springs Hospital, Central Australia. Participants were critically ill adult Indigenous and non-Indigenous Australian patients with a urinary catheter in situ. Exclusion criteria were anuria, pregnancy or the requirement for renal replacement therapy. Daily eight-hour measured creatinine clearances (CrCLm) were collected throughout the ICU stay. ARC was defined by a CrCLm ≥130 ml/min/1.73 m2. The Cockcroft-Gault and Chronic Kidney Disease Epidemiology Collaboration equations were also used to calculate mathematical estimates for comparison. In total, 131 patients were recruited (97 Indigenous, 34 non-Indigenous) and 445 samples were collected. The median (range) CrCLm was 93.0 (5.14 to 205.2) and 90.4 (18.7 to 206.8) ml/min/1.73 m2 in Indigenous and non-Indigenous patients, respectively. Thirty-one of 97 (32%) Indigenous patients manifested ARC, compared to 7 of 34 (21%) non-Indigenous patients (P=0.21). Younger age, major surgery, higher baseline renal function and an absence of diabetes were all associated with ARC. Both mathematical estimates manifest limited accuracy. ARC was prevalent in critically ill Indigenous patients, which places them at significant risk of underdosing with renally excreted drugs. CrCLm should be obtained wherever possible to ensure accurate dosing.
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Creatinina/urina , Cuidados Críticos/métodos , Taxa de Filtração Glomerular/fisiologia , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/urina , Austrália , Estudos de Coortes , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos ProspectivosRESUMO
BACKGROUND.: Perioperative administration of cefazolin reduces the incidence of perioperative infections. Intraoperative re-dosing of cefazolin is commonly given between 2 and 5 h after the initial dose. This study was undertaken to determine whether intraoperative continuous infusions of cefazolin achieve better probability of target attainment (PTA) and fractional target attainment (FTA) than intermittent dosing. METHODS.: Patients undergoing major surgery received cefazolin 2 g before surgical incision. They were subsequently randomized to receive either an intermittent bolus (2 g every 4 h) or continuous infusion (500 mg h -1 ) of cefazolin until skin closure. Blood samples were analysed for total and unbound cefazolin concentrations using a validated chromatographic method. Population pharmacokinetic modelling was performed using Pmetrics ® software. Calculations of PTA and FTA were performed for common pathogens. RESULTS.: Ten patients were enrolled in each arm. A two-compartment linear model best described the time course of the total plasma cefazolin concentrations. The covariates that improved the model were body weight and creatinine clearance. Protein binding varied with time [mean (range) 69 (44-80)%] with a fixed 21% unbound value of cefazolin used for the simulations (120 min post-initial dosing). Mean ( sd ) central volume of distribution was 5.73 (2.42) litres, and total cefazolin clearance was 4.72 (1.1) litres h -1 . Continuous infusions of cefazolin consistently achieved better drug exposures and FTA for different weight and creatinine clearances, particularly for less susceptible pathogens. CONCLUSIONS.: Our study demonstrates that intraoperative continuous infusions of cefazolin increase the achievement of target plasma concentrations, even with lower infusion doses. Renal function and body weight are important when considering the need for alternative dosing regimens. CLINICAL TRIAL REGISTRATION.: NCT02058979.
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Antibacterianos/administração & dosagem , Antibacterianos/farmacocinética , Antibioticoprofilaxia/métodos , Cefazolina/administração & dosagem , Cefazolina/farmacocinética , Procedimentos Cirúrgicos Operatórios , Adolescente , Adulto , Idoso , Peso Corporal , Creatinina/sangue , Feminino , Humanos , Infusões Intravenosas , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Ligação Proteica , Adulto JovemRESUMO
OBJECTIVES: To define standardized endpoints to aid the design of trials that compare antibiotic therapies for bloodstream infections (BSI). METHODS: Prospective studies, randomized trials or registered protocols comparing antibiotic therapies for BSI, published from 2005 to 2016, were reviewed. Consensus endpoints for BSI studies were defined using a modified Delphi process. RESULTS: Different primary and secondary endpoints were defined for pilot (small-scale studies designed to evaluate protocol design, feasibility and implementation) and definitive trials (larger-scale studies designed to test hypotheses and influence clinical practice), as well as for Staphylococcus aureus and Gram-negative BSI. For pilot studies of S. aureus BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever, stable/improved Sequential Organ Failure Assessment (SOFA) score and clearance of blood cultures, with no microbiologically confirmed failure up to 90 days. For definitive S. aureus BSI studies, a primary outcome of success at 90 days was defined by survival and no microbiologically confirmed failure. For pilot studies of Gram-negative BSI, a primary outcome of success at day 7 was defined by: survival, resolution of fever and symptoms related to BSI source, stable or improved SOFA score and negative blood cultures. For definitive Gram-negative BSI studies, a primary outcome of survival at 90 days supported by a secondary outcome of success at day 7 (as previously defined) was agreed. CONCLUSIONS: These endpoints provide a framework to aid future trial design. Further work will be required to validate these endpoints with respect to patient-centred clinical outcomes.
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Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Ensaios Clínicos como Assunto , Pesquisa Comparativa da Efetividade/normas , Determinação de Ponto Final/normas , Adulto , Infecções por Bactérias Gram-Negativas , Humanos , Infecções Estafilocócicas/tratamento farmacológico , Resultado do TratamentoRESUMO
Increasing rates of obesity in western populations present management difficulties for clinicians caring for obese pregnant women. Various governing bodies have published clinical guidelines for the care of obese parturients. These guidelines refer to two components of anaesthetic care: anaesthetic consultation in the antenatal period for women with a body mass index (BMI) ≥ 40 kg/m2 and the provision of early epidural analgesia in labour. These recommendations are based on the increased incidence of obstetric complications and the predicted risks and difficulties in providing anaesthetic care. The concept behind early epidural analgesia is logical-site the epidural early, use it for surgical anaesthesia and avoid general anaesthesia if surgery is required. Experts support this recommendation, but there is weak supporting evidence. It is known that the management of labour epidurals in obese women is complicated and that women with extreme obesity require higher rates of general anaesthesia. Anecdotally, anaesthetists view and apply the early epidural recommendation inconsistently and the acceptability of early epidural analgesia to pregnant women is variable. In this topic review, we critically appraise these two practice recommendations. The elements required for effective implementation in multidisciplinary maternity care are considered. We identify gaps in the current literature and suggest areas for future research. While prospective cohort studies addressing epidural extension ('top-up') in obese parturients would help inform practice, audit of local practice may better answer the question "is early epidural analgesia beneficial to obese women in my practice?".
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Anestesia Obstétrica/métodos , Obesidade/complicações , Guias de Prática Clínica como Assunto , Analgesia Epidural , Índice de Massa Corporal , Feminino , Humanos , Gravidez , Cuidado Pré-Natal , Encaminhamento e ConsultaRESUMO
Caring for obese pregnant women presents challenges for all medical professionals. Despite a lack of supporting evidence, expert opinion and international guidelines suggest early labour epidural insertion for obese women. Anecdotally this is not supported by all anaesthetists. This qualitative study explored the experiences of anaesthetists regarding early epidural analgesia in obese parturients, to answer the research question: Are anaesthetists consistent in how they apply early epidural analgesia in obese parturients? Personal in-depth interviews with 42 specialist anaesthetists working in south-east Queensland, Australia, were completed between February and April, 2015. Leximancer™ text analysis software applied a validated algorithm to the data to identify themes and concepts. The major themes were explored by the first author to answer the research question. Three major themes were identified: the demands associated with caring for obese women; concern regarding the anaesthetic technique used in obese women; and the importance of communication with obstetric staff. Disagreement regarding interpretation and application of early epidural analgesia was identified within this group of anaesthetists. These anaesthetists were inconsistent in how they interpreted and applied early epidural analgesia for obese parturients, with some questioning the validity of the practice. The combination of uncertainty, urgency and technical difficulty presented by obese parturients provoked anxiety in these clinicians, particularly the anticipation of unplanned general anaesthesia. Consistent anaesthetic practice could improve the implementation of early epidural analgesia in obese parturients.
Assuntos
Analgesia Epidural/métodos , Analgesia Obstétrica/métodos , Obesidade/complicações , Pesquisa Qualitativa , Adulto , Anestesistas , Comunicação , Feminino , Humanos , Masculino , GravidezRESUMO
OBJECTIVES: To use Monte Carlo simulation with an integrated pharmacokinetic-pharmacodynamic (PK-PD) model to evaluate guideline-recommended antimicrobial prophylaxis (AP) regimens with anaerobic coverage in abdominal surgery. METHODS: AP regimens were tested in simulated subjects undergoing elective abdominal surgery using relevant PK models and pathogen distributions in surgical site infections (SSIs). Predicted cumulative target attainment was the percentage of simulated subjects with free (unbound) antimicrobial plasma concentrations above the MICs for potential SSI pathogens. RESULTS: Cefazolin plus metronidazole covered SSI aerobes in 70% and the Bacteroides fragilis group in 99% of subjects, whereas cefoxitin only covered aerobes and anaerobes in 63% and 27% of cases, respectively. The broad-spectrum ceftriaxone plus metronidazole covered aerobes in 82% and anaerobes in 99% of simulations, while ertapenem covered aerobes in 88% and anaerobes in 90% of cases. Clindamycin covered the B. fragilis group in only 11% of cases. For cefazolin, 2 g doses maintained target attainment in simulated subjects from 80 to 120 kg, whereas 1 g doses were associated with lower target attainment against potential Gram-negative pathogens even in those <80 kg. For gentamicin, 3 mg/kg doses were comparable to the suggested 5 mg/kg, but superior to the traditional 1.5 mg/kg. CONCLUSIONS: This study demonstrates the use of PK-PD to inform decisions regarding AP in abdominal surgery. In this case, the findings support avoiding cefoxitin, avoiding clindamycin for anaerobic coverage, selecting 2 g doses of cefazolin even in patients <80 kg and using 3 mg/kg doses of gentamicin.
Assuntos
Abdome/cirurgia , Antibacterianos/administração & dosagem , Anti-Infecciosos/administração & dosagem , Antibioticoprofilaxia , Infecção da Ferida Cirúrgica/microbiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Abdome/microbiologia , Antibacterianos/farmacocinética , Antibacterianos/farmacologia , Anti-Infecciosos/farmacocinética , Anti-Infecciosos/farmacologia , Bactérias Anaeróbias/efeitos dos fármacos , Bacteroides fragilis/efeitos dos fármacos , Cefoxitina/administração & dosagem , Clindamicina/administração & dosagem , Simulação por Computador , Cálculos da Dosagem de Medicamento , Ertapenem , Feminino , Gentamicinas/administração & dosagem , Humanos , Masculino , Metronidazol/administração & dosagem , Testes de Sensibilidade Microbiana , Método de Monte Carlo , beta-Lactamas/administração & dosagemRESUMO
OBJECTIVES: Few data are available to guide linezolid dosing during renal replacement therapy. The objective of this study was to compare the population pharmacokinetics of linezolid during continuous venovenous haemofiltration (CVVHF, 30 mL/kg/h) and continuous venovenous haemodiafiltration (CVVHDF, 15 mL/kg/h + 15 mL/kg/h). METHODS: Patients requiring linezolid 600 mg iv every 12 h and CVVHF or CVVHDF were eligible for this prospective study. Seven blood samples were collected over one dosing interval and analysed by a validated chromatographic method. Population pharmacokinetic analysis was undertaken using Pmetrics. Monte Carlo simulations evaluated achievement of a pharmacodynamics target of an AUC from 0-24 h to MIC (AUC0-24/MIC) of 80. RESULTS: Nine CVVHDF and eight CVVHF treatments were performed in 13 patients. Regimens of CVVHDF and CVVHF were similar. A two-compartment linear model best described the data. CVVHDF was associated with a 20.5% higher mean linezolid clearance than CVVHF, without statistical significance (P = 0.39). Increasing patient weight and decreasing SOFA score were associated with increasing linezolid clearance. The mean (SD) parameter estimates were: clearance (CL), 3.8 (2.2) L/h; volume of the central compartment, 26.5 (10.3) L; intercompartmental clearance constants from central to peripheral, 8.1 (12.1) L/h; and peripheral to central compartments, 3.6 (4.0) L/h. Achievement of pharmacodynamic targets was poor for an MIC of 2 mg/L with the studied dose. CONCLUSIONS: During CVVHF and CVVHDF, there is profound pharmacokinetic variability of linezolid. Suboptimal achievement of therapeutic targets occurs at the EUCAST breakpoint MIC of 2 mg/L using 600 mg iv every 12 h.