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1.
Crit Care ; 27(1): 241, 2023 06 19.
Artigo em Inglês | MEDLINE | ID: mdl-37331935

RESUMO

BACKGROUND: In recent years, numerous dosing studies have been conducted to optimize therapeutic antibiotic exposures in patients with serious infections. These studies have led to the inclusion of dose optimization recommendations in international clinical practice guidelines. The last international survey describing dosing, administration and monitoring of commonly prescribed antibiotics for critically ill patients was published in 2015 (ADMIN-ICU 2015). This study aimed to describe the evolution of practice since this time. METHODS: A cross-sectional international survey distributed through professional societies and networks was used to obtain information on practices used in the dosing, administration and monitoring of vancomycin, piperacillin/tazobactam, meropenem and aminoglycosides. RESULTS: A total of 538 respondents (71% physicians and 29% pharmacists) from 409 hospitals in 45 countries completed the survey. Vancomycin was mostly administered as an intermittent infusion, and loading doses were used by 74% of respondents with 25 mg/kg and 20 mg/kg the most favoured doses for intermittent and continuous infusions, respectively. Piperacillin/tazobactam and meropenem were most frequently administered as an extended infusion (42% and 51%, respectively). Therapeutic drug monitoring was undertaken by 90%, 82%, 43%, and 39% of respondents for vancomycin, aminoglycosides, piperacillin/tazobactam, and meropenem, respectively, and was more frequently performed in high-income countries. Respondents rarely used dosing software to guide therapy in clinical practice and was most frequently used with vancomycin (11%). CONCLUSIONS: We observed numerous changes in practice since the ADMIN-ICU 2015 survey was conducted. Beta-lactams are more commonly administered as extended infusions, and therapeutic drug monitoring use has increased, which align with emerging evidence.


Assuntos
Antibacterianos , Vancomicina , Humanos , Adulto , Vancomicina/uso terapêutico , Meropeném , Estudos Transversais , Combinação Piperacilina e Tazobactam , Inquéritos e Questionários , Unidades de Terapia Intensiva , Aminoglicosídeos , Estado Terminal/terapia , Piperacilina
2.
J Antimicrob Chemother ; 77(12): 3358-3366, 2022 11 28.
Artigo em Inglês | MEDLINE | ID: mdl-36172897

RESUMO

BACKGROUND: Children with cystic fibrosis (CF) pulmonary exacerbations receive IV tobramycin therapy, with dosing guided by either log-linear regression (LLR) or Bayesian forecasting (BF). OBJECTIVES: To compare clinical and performance outcomes for LLR and BF. PATIENTS AND METHODS: A quasi-experimental intervention study was conducted at a tertiary children's hospital. Electronic medical records were extracted (from January 2015 to September 2021) to establish a database consisting of pre-intervention (LLR) and post-intervention (BF) patient admissions and relevant outcomes. All consecutive patients treated with IV tobramycin for CF pulmonary exacerbations guided by either LLR or BF were eligible. RESULTS: A total of 376 hospital admissions (LLR = 248, BF = 128) for CF pulmonary exacerbations were included. Patient demographics were similar between cohorts. There were no significant differences found in overall hospital length of stay, rates of re-admission within 1 month of discharge or change in forced expiratory volume in the first second (Δ FEV1) at the end of tobramycin treatment. Patients treated with LLR on average had twice the number of therapeutic drug monitoring (TDM) blood samples collected during a single hospital admission. The timeframe for blood sampling was more flexible with BF, with TDM samples collected up to 16 h post-tobramycin dose compared with 10 h for LLR. The tobramycin AUC0-24 target of ≥100 mg/L·h was more frequently attained using BF (72%; 92/128) compared with LLR (50%; 124/248) (P < 0.001). Incidence of acute kidney injury was rare in both groups. CONCLUSIONS: LLR and BF result in comparable clinical outcomes. However, BF can significantly reduce the number of blood collections required during each admission, improve dosing accuracy, and provide more reliable target concentration attainment in CF children.


Assuntos
Fibrose Cística , Infecções por Pseudomonas , Criança , Humanos , Tobramicina , Fibrose Cística/complicações , Fibrose Cística/tratamento farmacológico , Teorema de Bayes , Antibacterianos , Monitoramento de Medicamentos , Infecções por Pseudomonas/tratamento farmacológico
3.
Br J Clin Pharmacol ; 88(2): 669-679, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34289135

RESUMO

AIMS: The purpose of the study was to assess the status of emerging therapeutic drug monitoring (TDM) of anti-infective agents in Australian hospitals. METHODS: A nationwide cross-sectional survey of all Australian hospitals operating in the public and private health sector was conducted between August and September 2019. The survey consisted of questions regarding institutional TDM practice for anti-infective agents and clinical vignettes specific to ß-lactam antibiotics. RESULTS: Responses were received from 82 unique institutions, representing all Australian states and territories. All 29 (100%) of principal referral (major) hospitals in Australia participated. Five surveys were partially complete. Only 25% (20/80) of hospitals had TDM testing available on-site for any of the eight emerging TDM candidates considered: ß-lactam antibiotics, anti-tuberculous agents, flucytosine, fluoroquinolones, ganciclovir, human immunodeficiency virus (HIV) drugs, linezolid and teicoplanin. A considerable time lag was noted between TDM sampling and reporting of results. With respect to ß-lactam antibiotic TDM, variable indications, pharmacodynamic targets and sampling times were identified. The three greatest barriers to local TDM performance were found to be (1) lack of timely assays/results, (2) lack of institutional-wide expertise and/or training and (3) lack of guidelines to inform ordering of TDM and interpretation of results. The majority of respondents favoured establishing national TDM guidelines and increasing access to dose prediction software, at rates of 89% and 96%, respectively. CONCLUSION: Translating emerging TDM evidence into daily clinical practice is slow. Concerted efforts are required to address the barriers identified and facilitate the implementation of standardised practice.


Assuntos
Anti-Infecciosos , Monitoramento de Medicamentos , Antibacterianos/uso terapêutico , Anti-Infecciosos/uso terapêutico , Austrália , Estudos Transversais , Monitoramento de Medicamentos/métodos , Hospitais , Humanos , beta-Lactamas/uso terapêutico
4.
Eur J Clin Microbiol Infect Dis ; 37(11): 2171-2175, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30120647

RESUMO

To determine whether target concentration non-attainment can be anticipated in critically ill patients prior to initiating empiric ß-lactam antibiotic therapy based on readily available clinical factors. Retrospective review of consecutive patients treated with piperacillin or meropenem and who underwent therapeutic drug monitoring (TDM) at St Vincent's Hospital (Sydney, Australia) between January 2013 and December 2015 was performed. Predefined subgroups were patients who received continuous renal replacement therapy (CRRT) and those who did not (non-CRRT). Potential risk factors were evaluated by correlation with ß-lactam antibiotic trough concentrations (Cmin) lower than or equal to targeted minimum inhibitory concentration (MIC). Only the first drug concentration after initiation of the antibiotic treatment was included to reflect empirical dose selection. A total of n = 249 patients (piperacillin, n = 169; meropenem, n = 80) were investigated. For non-CRRT patients (n = 210), multivariate analysis demonstrated the following: male gender (p = 0.006); younger age (p = 0.015); prescribed daily antibiotic dose less than 1.5 times the product information recommendations (p = 0.004); lack of positive microbiology (p = 0.006); lower overall illness severity (p = 0.005); and estimated glomerular filtration rate (eGFR) ≥ 90 mL/min/1.73 m2 (p < 0.001), to be associated with Cmin ≤ MIC. No predictor variable was found to be significantly associated with Cmin ≤ MIC for the CRRT cohort. Evaluating the risk of target concentration non-attainment using simple clinical factors is possible at the bedside for non-CRRT patients prior to empiric antibiotic initiation. Clinicians should be wary of selecting doses based on the product information especially when treating younger male patients with apparently 'normal' renal function.


Assuntos
Antibacterianos/uso terapêutico , Estado Terminal/terapia , beta-Lactamas/uso terapêutico , Adulto , Idoso , Antibacterianos/farmacologia , Biomarcadores , Cromatografia Líquida de Alta Pressão , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Razão de Chances , Fatores de Risco , Espectrometria de Massas em Tandem , beta-Lactamas/farmacologia
5.
J Antimicrob Chemother ; 72(10): 2891-2897, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29091190

RESUMO

Objectives: To determine the existence of concentration-toxicity relationships for common ß-lactam antibiotic adverse effects and define thresholds above which toxicity is more likely. Patients and methods: Retrospective review of consecutive patients treated with piperacillin, meropenem or flucloxacillin who underwent therapeutic drug monitoring (TDM) at St Vincent's Hospital (Sydney, Australia) between January 2013 and December 2015. Adverse events investigated included neurotoxicity, nephrotoxicity, hepatotoxicity and opportunistic Clostridium difficile infection. Toxicity was measured using observational grading criteria, clinical assessment and relevant serum biomarkers. These findings were correlated with trough TDM measurements at the time of toxicity presentation. Results: TDM results from 378 patients (piperacillin = 223, meropenem = 94 and flucloxacillin = 61) were investigated. There was no difference in baseline patient characteristics across antibiotic groups. A statistically significant elevation in mean serum trough concentrations (Cmin) was found in patients diagnosed with neurotoxicity (piperacillin, P < 0.01; meropenem, P = 0.04; flucloxacillin, P = 0.01) and those who developed nephrotoxicity whilst being treated with piperacillin (P < 0.01) or meropenem (P < 0.01). Incidence of hepatotoxicity and C. difficile was not related to Cmin. Threshold concentrations for which there is 50% risk of developing a neurotoxicity event (piperacillin, Cmin >361.4 mg/L; meropenem, Cmin >64.2 mg/L; flucloxacillin, Cmin >125.1 mg/L) or nephrotoxicity (piperacillin, Cmin >452.65 mg/L; meropenem, Cmin >44.45 mg/L) varied across antibiotics. Conclusions: Our data reveal an association between toxic concentrations for a number of ß-lactam agents and neurotoxic/nephrotoxic effects. We have defined threshold concentrations above which these toxicities become more likely. Clinicians should balance concerns for therapeutic efficacy with potential toxicity when considering aggressive therapy.


Assuntos
Antibacterianos/efeitos adversos , beta-Lactamas/efeitos adversos , Adulto , Idoso , Antibacterianos/sangue , Antibacterianos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Infecções por Clostridium/etiologia , Estudos de Coortes , Monitoramento de Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Floxacilina/efeitos adversos , Floxacilina/sangue , Floxacilina/uso terapêutico , Humanos , Incidência , Masculino , Meropeném , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Síndromes Neurotóxicas/diagnóstico , Síndromes Neurotóxicas/etiologia , Piperacilina/efeitos adversos , Piperacilina/sangue , Piperacilina/uso terapêutico , Estudos Retrospectivos , Tienamicinas/efeitos adversos , Tienamicinas/sangue , Tienamicinas/uso terapêutico , beta-Lactamas/sangue , beta-Lactamas/uso terapêutico
7.
ANZ J Surg ; 94(7-8): 1383-1390, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38760999

RESUMO

BACKGROUND: Diabetic foot ulcers (DFUs) are a challenging complication of diabetes mellitus, often leading to poor clinical outcomes and significant socioeconomic burdens. We evaluated the effectiveness of a definitive single-stage protocolized surgical management pathway, including the use of local antibiotic bone graft substitute, for the treatment of infected DFUs with associated osteomyelitis. METHODS: A retrospective cohort study was conducted. Medical records were extracted (from January 2017 to December 2020) to establish a database consisting of patients who underwent surgical intervention for the treatment of an infected DFU with osteomyelitis. Patients were divided into conventional (control) and protocolized (intervention) surgical groups depending on the treatment received. Clinical outcomes were assessed over a 12-month follow-up period. RESULTS: A total of 136 consecutive patients were included (conventional = 33, protocolized = 103). The protocolized group demonstrated a statistically significant reduction in the mean number of operations performed per patient (1.2 vs. 3.5) (P < 0.001) and a shorter accumulative hospital length of stay (12.6 vs. 25.1 days) (P < 0.001) compared to the conventional group. Major amputation rates were significantly lower in the protocolized group (2% vs. 18%) (P < 0.001). Within 12 months of surgical intervention, the protocolized group exhibited an ulcer healing rate of 89%, with a low rate of recurrence (3%). CONCLUSION: The protocolized surgical pathway, including local antibiotic bone graft substitute use, demonstrated superior outcomes compared to conventional management for the treatment of infected DFUs with osteomyelitis. Further research is needed to evaluate the cost-effectiveness and generalizability of this approach.


Assuntos
Antibacterianos , Substitutos Ósseos , Pé Diabético , Osteomielite , Humanos , Pé Diabético/cirurgia , Pé Diabético/complicações , Osteomielite/cirurgia , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Antibacterianos/uso terapêutico , Idoso , Substitutos Ósseos/uso terapêutico , Resultado do Tratamento , Protocolos Clínicos , Amputação Cirúrgica/métodos , Amputação Cirúrgica/estatística & dados numéricos , Desbridamento/métodos
8.
Int J Antimicrob Agents ; 64(2): 107192, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38734215

RESUMO

BACKGROUND: Therapeutic drug monitoring (TDM) is an effective method for individualising antimicrobial therapy in critically ill patients. The 2021 ADMIN-intensive care unit survey studied a wide range of intensive care unit clinicians worldwide to gain their perspectives on antimicrobial TDM. This article reports the responses from this survey relating to TDM access, utilisation, and barriers. METHODS: An online survey consisted of multiple-choice questions and 5-point Likert scales. The survey examined respondent's access to minimum inhibitory concentration (MIC) results, drug assays, and dosing software, as well as barriers to TDM. RESULTS: The survey included 538 clinicians from 409 hospitals in 45 countries, with 71% physicians and 29% pharmacists. Despite most respondents having access to assays, 21% and 26% of respondents lacked access to vancomycin and aminoglycosides, respectively. In lower-income countries, almost 40% reported no access. Delayed drug assay turnaround time was the most significant barrier to TDM, particularly in lower-income countries. Routine access to MIC results was unavailable for 41% of respondents, with 25% of lower-income country respondents having no access to MIC or susceptibility reports. CONCLUSIONS: This global survey indicated that consistent TDM usage is hindered by assay access in some sites and the timeliness of assay results in others. Addressing barriers to TDM, particularly in low-income countries, should be a priority to ensure equitable access to affordable TDM.


Assuntos
Antibacterianos , Estado Terminal , Monitoramento de Medicamentos , Testes de Sensibilidade Microbiana , Humanos , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/estatística & dados numéricos , Inquéritos e Questionários , Antibacterianos/uso terapêutico , Unidades de Terapia Intensiva , Adulto , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Vancomicina/uso terapêutico , Vancomicina/farmacocinética , Saúde Global
9.
J Hand Surg Asian Pac Vol ; 28(5): 539-547, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37881822

RESUMO

Background: Literature investigating the long-term outcomes of prosthesis options for proximal interphalangeal (PIP) joint arthroplasty is scarce, with most reports combining indications and underlying pathologies in analyses. In this study, we aim to compare silicone, pyrocarbon and metal prostheses in PIP joint arthroplasty for primary degenerative osteoarthritis (OA). Methods: A review of scientific literature published between 1990 and 2021 was conducted. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. Relevant studies were screened and the appropriate data was extracted. An evaluation of clinical outcomes (range of motion [ROM] and pain), complications (reoperation) and survival rates for each prosthesis was performed. Results: Twelve studies were included for analysis with a total of 412 PIP joints. ROM was 66.6°, 55.8° and 46.4° for metal, silicone and pyrocarbon implants, respectively. Silicone implants had the best pain score on the visual analogue scale (1.2) followed by the pyrocarbon (2.6) and metal (3.9) groups. Complication rates were lowest in silicone implants (11.3%) compared to 18.5% in pyrocarbon and 22.4% in metal prostheses. Survival did not differ significantly amongst the three groups. Conclusions: Our findings suggest that for patients with primary degenerative OA, PIP joint arthroplasty using a silicone prosthesis can provide greater pain relief with lower complication rates compared to other implant options. Level of Evidence: Level III (Therapeutic).


Assuntos
Artroplastia de Substituição de Dedo , Prótese Articular , Osteoartrite , Humanos , Articulações dos Dedos/cirurgia , Osteoartrite/cirurgia , Artroplastia , Silicones , Dor
10.
IDCases ; 25: e01211, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34277350

RESUMO

BACKGROUND: Achromobacter xylosoxidans is an opportunistic environmental aerobe. In cases where A. xylosoxidans infects humans, it most commonly manifests as bacteraemia in the immunosuppressed. A. xylosoxidans causing chronic osteomyelitis is rare, particularly in the immunocompetent and young. CASE: We present the case of a 23-year-old man with chronic osteomyelitis of the right femur caused by co-infection of A. xylosoxidans and Staphylococcus aureus. Five years earlier, he had sustained a right femur fracture and was treated with intramedullary fixation at a peripheral hospital in a developing nation. Past medical history was otherwise unremarkable. Management comprised of surgical debridement and culture-directed antibiotic therapy, resulting in clinical cure. CONCLUSION: In the context of local trauma and previous surgery, osteomyelitis caused by atypical pathogens must be considered. A multidisciplinary approach commensurate with duration and severity of infection and tailored to the causative organism is paramount.

11.
ANZ J Surg ; 91(12): 2773-2779, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34582083

RESUMO

BACKGROUND: Rotator cuff tears are a common shoulder pathology with an increasing incidence. The optimum post-operative rehab protocol remains unclear and can consist of either conservative rehabilitation or more aggressive early range-of-motion. Multiple studies have assessed these treatment protocols. This meta-analysis aims to compare post-operative clinical outcomes following either conservative or aggressive rehabilitation post rotator cuff repair. METHODS: A systematic electronic literature search was undertaken using a number of databases. Eligible studies included randomized control trials published between January 2013 and April 2019 in English with patients having had received rotator cuff repair. Post-operative clinical outcomes considered included shoulder range-of-motion, overall function status (Costant-Murley score) and rates of rotator-cuff re-tear. Studies were evaluated for methodological quality in accordance with the Physiotherapy Evidence Database (PEDro) scale. Summarized pooled statistics were calculated using Review Manager (v5.3) software. RESULTS: A total of six randomized controlled trials were included. Standardized mean difference (SMD) in shoulder flexion, abduction and external rotation was not statistically significant at either 6 or 12 months post rotator cuff repair. Functional assessment suggests a slight benefit in Constant-Murley Score (SMD = 1.77; 95% CI -3.93, 7.47) in aggressive treatment groups with no significant risk increase for cuff re-tear (RR = 1.22; 95% CI 0.60, 2.47). CONCLUSION: This meta-analysis suggests there is no clear benefit of either rehabilitation protocol when considering range-of-motion, with a possible benefit in functional outcome at the cost of increased re-tear risk post aggressive rehabilitation. Both protocols have been shown to offer safe reproducible short- and long-term outcomes.


Assuntos
Lacerações , Lesões do Manguito Rotador , Humanos , Metanálise como Assunto , Manguito Rotador/cirurgia , Lesões do Manguito Rotador/cirurgia
12.
BMJ Case Rep ; 13(1)2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31969416

RESUMO

A 32-year-old man presented with a 7-day history of generalised headache, intermittent fever, emesis and diarrhoea. Four days after symptom onset, he developed a vesicular rash on his medial left thigh, without associated pain, paraesthesia or pruritus. He had no significant past medical history, and no HIV risk factors. He was presumed to have enteroviral meningitis and was commenced on supportive therapy. Lumbar puncture was performed and cerebrospinal fluid (CSF) analysis revealed a lymphocytic pleocytosis. While awaiting CSF serology, the formation of a new vesicle was noted at the site of the rash and was swabbed. Results for both the CSF and vesicle swab returned positive for varicella-zoster virus (VZV) confirming concurrent VZV meningitis with atypical painless herpes zoster in a young immunocompetent patient. He was initiated on intravenous acyclovir and made a full recovery after 2 weeks of treatment.


Assuntos
Aciclovir/uso terapêutico , Herpes Zoster/tratamento farmacológico , Herpesvirus Humano 3/efeitos dos fármacos , Meningite Viral/tratamento farmacológico , Adulto , Antivirais/uso terapêutico , Diagnóstico Diferencial , Humanos , Masculino
13.
Int J Antimicrob Agents ; 56(6): 106180, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32987102

RESUMO

When performed according to best-practice principles, therapeutic drug monitoring (TDM) can optimise anti-infective treatment and directly benefit clinical outcomes. We evaluated TDM performance and clinical decision-making for established anti-infective agents amongst Australian hospitals. A nationwide cross-sectional survey was conducted between August and September 2019. The survey consisted of multiple-choice questions regarding TDM of anti-infective agents in general as well as clinical vignettes specific to vancomycin, gentamicin and voriconazole. We sought to survey all Australian hospitals operating both in the public and private health sectors. Responses were captured from 85 unique institutions, from all Australian states and territories. Regarding guidelines, 26% of hospitals did not have endorsed guidelines to advise on the ordering, sampling and interpretation of TDM for any anti-infective agent. Admitting teams were predominantly responsible for ordering TDM (85%) and interpreting results (76%). Only 51% of hospitals had access to dose prediction software, with access generally better amongst principal referral (69%) (P = 0.01) and children's hospitals (100%) (P = 0.04). Whenever a laboratory-derived minimum inhibitory concentration (MIC) was not available to guide dosing decisions, a surrogate target MIC was assumed in 77% of hospitals. This was based on a 'worst-case' scenario infection in 11% of hospitals. The rates of clinical practice consistent with current guideline recommendations across all aspects of TDM were demonstrated to be 0% for vancomycin, 4% for gentamicin and 35% for voriconazole. At present, there is significant institutional variability in the clinical practice of TDM for anti-infective agents in Australia for established TDM drugs.


Assuntos
Anti-Infecciosos/uso terapêutico , Tomada de Decisão Clínica , Gentamicinas/uso terapêutico , Vancomicina/uso terapêutico , Voriconazol/uso terapêutico , Austrália , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Estudos Transversais , Monitoramento de Medicamentos/métodos , Fungos/efeitos dos fármacos , Pessoal de Saúde/psicologia , Humanos , Testes de Sensibilidade Microbiana , Micoses/tratamento farmacológico , Inquéritos e Questionários
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