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BACKGROUND: The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. METHODS: We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. RESULTS: Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of -1.4 percentage points (90% confidence interval [CI], -4.9 to 2.2; 95% CI, -5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%). CONCLUSIONS: Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927 .).
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Administração Oral , Antibacterianos/administração & dosagem , Doenças Ósseas Infecciosas/tratamento farmacológico , Artropatias/tratamento farmacológico , Administração Intravenosa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Antibacterianos/farmacocinética , Feminino , Humanos , Análise de Intenção de Tratamento , Masculino , Adesão à Medicação , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Reducing antibiotic use is central to antimicrobial stewardship, but may have unintended consequences. OBJECTIVES: To examine associations between size of decline in antibiotic prescriptions in general practices and (i) rate of hospitalization for infection and (ii) patient satisfaction. METHODS: Routine data analysis for all general practices in Scotland, quarter one 2012 (Q1 2012) to quarter one 2018 (Q1 2018). Practices were grouped into quartiles of rate of change in prescribing and changes in rates of hospitalization were compared across groups. For satisfaction analysis, associations between practice-level patient satisfaction in 2017-18 (Scottish Health and Care Experience Survey) and prior change in antibiotic prescription were examined. RESULTS: Antibiotic prescriptions overall fell from 194.1 prescriptions/1000 patients in Q1 2012 to 165.3 in Q1 2018 (14.9% reduction). The first quartile of practices had a non-significant increase in prescriptions [change per quarterâ=â0.22 (95% CI -0.42 to 0.86) prescriptions/1000 patients], compared with large reductions in the other three groups, largest in quartile four: -2.95 (95% CI -3.66 to -2.24) prescriptions/1000 patients/quarter (29.7% reduction overall). In all quartiles, hospitalizations with infection increased. The increase was smallest in quartile four (the biggest reduction in prescriptions) and highest in quartile one (no significant change in prescriptions): 2.18 (95% CI 1.18 to 3.19) versus 3.68 (95% CI 2.64 to 4.73) admissions/100â000 patients/quarter, respectively [differenceâ=â-â1.50 (95% CI -2.91 to -0.10)]. There was no statistically significant association between change in antibiotic prescriptions and patient satisfaction. CONCLUSIONS: Very large reductions in antibiotic prescriptions in Scottish general practices have not been associated with increases in hospitalization with infection or changes in patient satisfaction.
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Antibacterianos , Gestão de Antimicrobianos , Antibacterianos/uso terapêutico , Prescrições de Medicamentos , Hospitalização , Humanos , Padrões de Prática Médica , Atenção Primária à Saúde , Escócia/epidemiologiaRESUMO
OBJECTIVES: To evaluate the effect of general practice-level prescribing feedback on antibiotic prescribing in a real-world pragmatic cluster randomized controlled trial. METHODS: Three hundred and forty general practices in four territorial Health Boards in NHS Scotland were randomized in Quarter 1, 2016 to receive four quarterly antibiotic-prescribing feedback reports or not, from Quarter 2, 2016 to Quarter 1, 2017. Reports included different clinical topics, benchmarking against national and health board rates, and behavioural messaging with improvement actions. The primary outcome was total antibiotic prescribing rate. There were 16 secondary prescribing outcomes and 5 hospital admission outcomes (potential adverse effects of reduced prescribing). The main evaluation timepoint was 1â year after the final report (Quarter 1, 2018), with an additional evaluation in the quarter after the final report (Quarter 2, 2017). Routine administrative NHS data were used to generate the feedback reports and analyse the effects. RESULTS: Total antibiotic prescribing rates were lower at the main evaluation timepoint in both intervention (1.83 versus baseline 1.93 prescriptions/1000â patients/day) and control (1.90 versus baseline 1.98) practices, with no evidence of intervention effect [adjusted rate ratio (ARR) 0.98 (95% CI 0.94-1.02; Pâ=â0.35)]. At the additional timepoint, adjusted total antibiotic prescribing rates were 1.67 and 1.73 prescriptions/1000â patients/day, with evidence of a small intervention effect, ARR 0.99 (0.98-1.00; Pâ=â0.03). CONCLUSIONS: This well-designed, practice-level antibiotic-prescribing feedback had limited evidence of additional effects in the context of decreasing antibiotic prescribing and an established national stewardship programme.
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Antibacterianos , Medicina Geral , Humanos , Antibacterianos/uso terapêutico , Retroalimentação , Escócia , Atenção Primária à Saúde/métodos , Padrões de Prática Médica , Prescrição InadequadaRESUMO
Introduction Guidelines on the length of treatment of dental infections with systemic antibiotics vary across different countries. We aimed to determine if short-duration (3-5 days) courses of systemic antibiotics were as effective as longer-duration courses (≥7 days) for the treatment of dental infections in adults in outpatient settings.Methods We searched Ovid Medline, Ovid Embase, Cochrane, trials registries, Google Scholar and forward and backward citations for studies published between database inception and 30 March 2021. All randomised clinical trials (RCT) and non-randomised trials which compared length of treatment with systemic antibiotics for dental infections in adults in outpatient settings published in English were included.Results One small RCT met our defined inclusion criteria. The trial compared three-day versus seven-day courses of amoxicillin in adults with odontogenic infection requiring tooth extraction. There was no significant difference between groups in terms of participant-reported pain or clinical assessment of wound healing.Discussion While a number of observational studies were supportive of shorter-course therapy, only one small RCT concluded that a three-day course of amoxicillin was clinically non-inferior versus seven days for the treatment of odontogenic infection requiring tooth extraction. Limited conclusions on shorter-course therapy can be drawn from this study as all participants commenced amoxicillin two days before tooth extraction which is not common clinical practice. The variability in guidelines for use of antimicrobials in dental infections suggests that guidelines are based on local or national historical practice and indicates the need for further research to determine the optimum length of treatment. RCTs are required to investigate if short-duration courses of antibiotics are effective and to provide evidence to support consistent guidance for dental professionals.
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BACKGROUND: Scottish Antimicrobial Prescribing Group (SAPG) recommendations to reduce broad-spectrum antimicrobial use led to an increase in gentamicin and vancomycin prescribing. In 2009, SAPG introduced national guidance to standardize dosage regimens, reduce calculation errors and improve the monitoring of these antibiotics. Studies conducted in 2010 and 2011 identified limitations in guideline implementation. OBJECTIVES: To develop, implement and assess the long-term impact of quality improvement (QI) resources to support gentamicin and vancomycin prescribing, administration and monitoring. METHODS: New resources, comprising revised guidelines, online and mobile app dose calculators, educational material and specialized prescribing and monitoring charts were developed in collaboration with antimicrobial specialists and implemented throughout Scotland during 2013-16. An online survey in 2017 evaluated the use of these resources and a before (2011) and after (2018) point prevalence study assessed their impact. RESULTS: All 12 boards who responded to the survey (80%) were using the guidance, electronic calculators and gentamicin prescription chart; 8 used a vancomycin chart. The percentage of patients who received the recommended gentamicin dose increased from 44% to 89% (OR 10.99, 95% CI = 6.37-18.95) between 2011 and 2018. For vancomycin, the correct loading dose increased from 50% to 85% (OR = 5.69, CI = 2.76-11.71) and the correct maintenance dose from 55% to 90% (OR = 7.17, CI = 3.01-17.07). CONCLUSIONS: This study demonstrated improvements in the national prescribing of gentamicin and vancomycin through the development and coordinated implementation of a range of QI resources and engagement with local and national multidisciplinary teams.
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Gentamicinas , Vancomicina , Antibacterianos/uso terapêutico , Humanos , Melhoria de Qualidade , Escócia , Vancomicina/uso terapêuticoRESUMO
Outpatient parenteral antimicrobial therapy (OPAT) offers safe, effective and patient-centred care for adults and children. The OPAT UK good practice recommendations for adults and children have recently been updated through a process of literature review, expert consensus and extensive stakeholder consultation. Here we discuss the key changes in the updated recommendations in the context of recent developments, including novel antimicrobial agents and delivery devices, the place of oral antimicrobials as an alternative to intravenous therapy, new OPAT service models and the broader antimicrobial stewardship agenda.
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Assistência Ambulatorial , Antibacterianos/uso terapêutico , Infusões Parenterais/métodos , Guias de Prática Clínica como Assunto , Adulto , Assistência Ambulatorial/economia , Assistência Ambulatorial/normas , Antibacterianos/administração & dosagem , Gestão de Antimicrobianos , Criança , Humanos , Reino UnidoRESUMO
BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is associated with significant morbidity and mortality and has resultant important economic and societal costs underscoring the need for accurate surveillance. In recent years, prevalence rates reported in East Africa have been inconsistent, sparking controversy and raising concern. METHODS: We described antimicrobial susceptibility patterns of Staphylococcus aureus isolates cultured from patients within the Internal Medicine department of the largest public healthcare facility in East and Central Africa- the Kenyatta National Hospital (KNH) in Nairobi, Kenya. Routine antimicrobial susceptibility data from non-duplicate Staphylococcus aureus isolates cultured between the years 2014-2016 from the medical wards in KNH were reviewed. RESULTS: Antimicrobial susceptibility data from a total of 187 Staphylococcus aureus isolates revealed an overall MRSA prevalence of 53.4%. Isolates remained highly susceptible to linezolid, tigecycline, teicoplanin and vancomycin. CONCLUSIONS: The prevalence of MRSA was found to be much higher than that reported in private tertiary facilities in the same region. Careful interrogation of antimicrobial susceptibility results is important to uproot any red herrings and reserve genuine cause for alarm, as this has a critical bearing on health and economic outcomes for a population.
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Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/diagnóstico , Adulto , África Oriental/epidemiologia , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cefoxitina/farmacologia , Cefoxitina/uso terapêutico , Feminino , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Prevalência , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/isolamento & purificaçãoRESUMO
BACKGROUND: There are thousands of survivors of the 2014 Ebola outbreak in west Africa. Ebola virus can persist in survivors for months in immune-privileged sites; however, viral relapse causing life-threatening and potentially transmissible disease has not been described. We report a case of late relapse in a patient who had been treated for severe Ebola virus disease with high viral load (peak cycle threshold value 13.2). METHODS: A 39-year-old female nurse from Scotland, who had assisted the humanitarian effort in Sierra Leone, had received intensive supportive treatment and experimental antiviral therapies, and had been discharged with undetectable Ebola virus RNA in peripheral blood. The patient was readmitted to hospital 9 months after discharge with symptoms of acute meningitis, and was found to have Ebola virus in cerebrospinal fluid (CSF). She was treated with supportive therapy and experimental antiviral drug GS-5734 (Gilead Sciences, San Francisco, Foster City, CA, USA). We monitored Ebola virus RNA in CSF and plasma, and sequenced the viral genome using an unbiased metagenomic approach. FINDINGS: On admission, reverse transcriptase PCR identified Ebola virus RNA at a higher level in CSF (cycle threshold value 23.7) than plasma (31.3); infectious virus was only recovered from CSF. The patient developed progressive meningoencephalitis with cranial neuropathies and radiculopathy. Clinical recovery was associated with addition of high-dose corticosteroids during GS-5734 treatment. CSF Ebola virus RNA slowly declined and was undetectable following 14 days of treatment with GS-5734. Sequencing of plasma and CSF viral genome revealed only two non-coding changes compared with the original infecting virus. INTERPRETATION: Our report shows that previously unanticipated, late, severe relapses of Ebola virus can occur, in this case in the CNS. This finding fundamentally redefines what is known about the natural history of Ebola virus infection. Vigilance should be maintained in the thousands of Ebola survivors for cases of relapsed infection. The potential for these cases to initiate new transmission chains is a serious public health concern. FUNDING: Royal Free London NHS Foundation Trust.
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Alanina/análogos & derivados , Antivirais/uso terapêutico , Ebolavirus/isolamento & purificação , Doença pelo Vírus Ebola/diagnóstico , Meningoencefalite/diagnóstico , Meningoencefalite/virologia , Ribonucleotídeos/uso terapêutico , Carga Viral/efeitos dos fármacos , Doença Aguda , Monofosfato de Adenosina/análogos & derivados , Adulto , Alanina/uso terapêutico , Doenças dos Nervos Cranianos/virologia , Surtos de Doenças , Drogas em Investigação/uso terapêutico , Ebolavirus/genética , Feminino , Genoma Viral , Doença pelo Vírus Ebola/tratamento farmacológico , Humanos , Meningoencefalite/complicações , Meningoencefalite/tratamento farmacológico , Enfermeiras e Enfermeiros , RNA Viral/sangue , RNA Viral/líquido cefalorraquidiano , RNA Viral/isolamento & purificação , Radiculopatia/virologia , Recidiva , Escócia , Serra LeoaRESUMO
BACKGROUND: Pooled data from two large registries, Cubicin(®) Outcomes Registry and Experience (CORE; USA) and European Cubicin(®) Outcomes Registry and Experience (EU-CORE; Europe, Latin America, and Asia), were analyzed to determine the characteristics and clinical outcomes of daptomycin therapy in patients with Gram-positive infections across wide geographical regions. METHODS: Patients receiving at least one dose of daptomycin between 2004 and 2012 for the treatment of Gram-positive infections were included. Clinical success was defined as an outcome of 'cured' or 'improved'. Post-treatment follow-up data were collected for a subset of patients (CORE: osteomyelitis and orthopedic foreign body device infection; EU-CORE: endocarditis, intracardiac/intravascular device infection, osteomyelitis, and orthopedic device infection). Safety was assessed for up to 30 days after daptomycin treatment. RESULTS: In 11,557 patients (CORE, 5482; EU-CORE, 6075) treated with daptomycin (median age, 62 [range, 1-103] years), the most frequent underlying conditions were cardiovascular disease (54.7 %) and diabetes mellitus (28.0 %). The most commonly treated primary infections were complicated skin and soft tissue infection (cSSTI; 31.2 %) and bacteremia (21.8 %). The overall clinical success rate was 77.2 % (uncomplicated SSTI, 88.3 %; cSSTI, 81.0 %; osteomyelitis, 77.7 %; foreign body/prosthetic infection (FBPI), 75.9 %; endocarditis, 75.4 %; and bacteremia, 69.5 %). The clinical success rate was 79.1 % in patients with Staphylococcus aureus infections (MRSA, 78.1 %). An increasing trend of high-dose daptomycin (>6 mg/kg/day) prescribing pattern was observed over time. Clinical success rates were higher with high-dose daptomycin treatment for endocarditis and FBPI. Adverse events (AEs) and serious AEs possibly related to daptomycin therapy were reported in 628 (5.4 %) and 133 (1.2 %) patients, respectively. CONCLUSIONS: The real-world data showed that daptomycin was effective and safe in the treatment of various Gram-positive infections, including those caused by resistant pathogens, across wide geographical regions.
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Antibacterianos/uso terapêutico , Daptomicina/uso terapêutico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ásia , Criança , Pré-Escolar , Europa (Continente) , Feminino , Bactérias Gram-Positivas/efeitos dos fármacos , Bactérias Gram-Positivas/fisiologia , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Lactente , Recém-Nascido , América Latina , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Resultado do Tratamento , Estados Unidos , Adulto JovemRESUMO
[This corrects the article DOI: 10.1371/journal.pone.0272375.].
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OBJECTIVES: To investigate the stability of aciclovir solutions in elastomeric devices used for outpatient parenteral antimicrobial therapy (OPAT). METHODS: Triplicates of two elastomeric devices, Accufuser and Easypump II, were filled with a solution of 200 mg, 2400 mg, and 4500 mg aciclovir in 240 mL 0.9% w/v saline. Devices were stored at room temperature for 14 days, followed by 24 hours storage at 32°C. Assessment using a stability indicating assay, pH and subvisible particle analysis was undertaken at 11 time points throughout the study. RESULTS: Aciclovir solution at 200 mg and 2400 mg in 240 mL was stable for 14 days at room temperature (<20°C) and 24 hours of 32°C 'in-use' temperature exposure, remaining above the 95% limit for NHS stability protocols. The high dose was also stable for 14 days at room temperature, but when stored at 32°C there was precipitation of aciclovir within 4 hours in both devices. The precipitate was confirmed as aciclovir and precipitation was not a sign of chemical degradation. CONCLUSIONS: Aciclovir concentrations above 2400 mg/240 mL are liable to precipitation and cannot be recommended for OPAT services because of heightened risks of nephrotoxicity. Aciclovir solution can be given as a continuous 24-hour infusion for OPAT services at a concentration range of 200-2400 mg in 240 mL in Accufuser and Easypump II elastomeric devices following 14 days storage at room temperature, protected from light.
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The UK Antimicrobial Registry (UKAR) has been developed to capture data on real world usage of antimicrobial agents with an initial focus on those used to treat drug-resistant infections. Several industry partners have committed support for the study, which is included in the National Institute for Health and Care Research (NIHR) portfolio in England with similar arrangements in the three devolved UK nations. The two antimicrobials in the National Institute for Health and Care Excellence (NICE) subscription model pilot (cefiderocol and ceftazidime/avibactam) are included in the UKAR and future expansion of work in this area is planned. This model decouples payment from usage by using a fixed annual fee. The study will provide information on the characteristics of patients receiving study drugs, the infections being treated, treatment effectiveness and adverse events. UKAR potentially provides a novel resource of enduring value to support healthcare in the UK and more widely and contribute to AMR National Action Plan goals for optimal use of antimicrobials.
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Objectives: To evaluate the stability of ceftazidime/avibactam in elastomeric infusers, utilizing the UK's Yellow Cover Document (YCD) stability testing framework, in conditions representative of OPAT practice. Methods: Ceftazidime/avibactam was reconstituted with sodium chloride 0.9% (w/v) in two elastomeric infusers at concentrations (dose) levels of 1500/375, 3000/750 and 6000â mg/1500â mg in 240â mL. The infusers were exposed to a fridge storage (2°C-8°C) for 14â days followed by 24â h in-use temperature (32°C). Results: After 14â days of fridge storage and subsequent 24â h exposure to 32°C, meanâ±âSD of ceftazidime percent remaining was 75.5%â±â1.8%, 79.9%â±â1.1%, 82.4%â±â0.6%, for Easypump, and 81.7%â±â1.2%, 82.5%â±â0.5%, 85.4%â±â1.1% for Dosi-Fuser devices at the high, intermediate and low doses tested, respectively. For avibactam, meanâ±âSD percent remaining was 83.2%â±â1.8%, 87.4%â±â2.0%, 93.1%â±â0.9% for Easypump, and 85.1%â±â2.0%, 86.7%â±â0.1%, 92.5%â±â0.1% for Dosi-Fuser devices. The cumulative amount of pyridine generated in the devices ranged from 10.4â mg at low dose to 76.9â mg at high dose. Regression-based simulation showed that the degradation of both ceftazidime and avibactam was <10% for at least 12â h of the running phase, if stored in a fridge for not more than 72â h prior to in-use temperature exposure. Conclusions: Whilst not meeting the strict UK YCD criteria for ≤5% degradation, ceftazidime/avibactam may be acceptable to administer as a continuous 12â hourly infusion in those territories where degradation of ≤10% is deemed acceptable.
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OBJECTIVES: To identify risk factors for failure of outpatient antibiotic therapy (OPAT) in infective endocarditis (IE). PATIENTS AND METHODS: We identified IE cases managed at a single centre over 12 years from a prospectively maintained database. 'OPAT failure' was defined as unplanned readmission or antibiotic switch due to adverse drug reaction or antibiotic resistance. We analysed patient and disease-related risk factors for OPAT failure by univariate and multivariate logistic regression. We also retrospectively collected follow-up data on adverse disease outcome (defined as IE-related death or relapse) and performed Kaplan-Meier survival analysis up to 36 months following OPAT. RESULTS: We identified 80 episodes of OPAT in IE. Failure occurred in 25/80 episodes (31.3%). On multivariate analysis, cardiac or renal failure [pooled OR 7.39 (95% CI 1.84-29.66), P=0.005] and teicoplanin therapy [OR 8.69 (95% CI 2.01-37.47), P=0.004] were independently associated with increased OPAT failure. OPAT failure with teicoplanin occurred despite therapeutic plasma levels. OPAT failure predicted adverse disease outcome up to 36 months (P=0.016 log-rank test). CONCLUSIONS: These data caution against selecting patients with endocarditis for OPAT in the presence of cardiac or renal failure and suggest teicoplanin therapy may be associated with suboptimal OPAT outcomes. Alternative regimens to teicoplanin in the OPAT setting should be further investigated.
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Administração Intravenosa/métodos , Assistência Ambulatorial/métodos , Antibacterianos/administração & dosagem , Endocardite/tratamento farmacológico , Idoso , Antibacterianos/efeitos adversos , Farmacorresistência Bacteriana , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Falha de TratamentoRESUMO
OBJECTIVES: Infective endocarditis (IE) is a complex infection associated with high mortality. Daptomycin, a cyclic lipopeptide antibiotic highly active against Gram-positive bacteria, has recently been incorporated into IE treatment guidelines. This retrospective analysis provides insights into the use of daptomycin in IE in the European Cubicin(®) Outcomes Registry Experience (EU-CORE(SM)) between 2006 and 2010. PATIENTS AND METHODS: Three hundred and seventy-eight (10%) of 3621 enrolled patients received daptomycin for treatment of IE. Two hundred and fifty-nine (69%) had left-sided IE (LIE) and 182 patients (48%) underwent concomitant surgery. RESULTS: Staphylococcus aureus was the most frequently identified pathogen (n=92; methicillin susceptible, n=50) and daptomycin was used empirically in 134 patients. Among cases of second-line therapy (n=312), the most common reason for switching to daptomycin was failure of the previous regimen (including glycopeptides and penicillins). Daptomycin was administered at 6 mg/kg in 224 patients and at ≥ 8 mg/kg in 72 patients. Clinical success rates were 80% overall, 91% for right-sided IE (RIE) and 76% for LIE, with similar rates seen for infections caused by methicillin-susceptible S. aureus (84%) and methicillin-resistant S. aureus (81%). The clinical success rate in patients treated with ≥ 8 mg/kg daptomycin was 90% [n=72 (RIE, 91%; LIE, 89%)]. No new safety signals were observed. CONCLUSIONS: In patients with IE registered in EU-CORE, daptomycin was most frequently used as second-line treatment after treatment failure. The majority of patients had LIE and most commonly received daptomycin for the treatment of staphylococcal infections. Clinical success was high in this difficult-to-treat population. The role of doses ≥ 8 mg/kg per day in the empirical treatment of IE deserves further investigation.
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Antibacterianos/uso terapêutico , Daptomicina/uso terapêutico , Endocardite/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Europa (Continente) , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sistema de Registros/estatística & dados numéricos , Estudos Retrospectivos , Terapia de Salvação/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Osteomyelitis is a complex and heterogeneous group of infections that require surgical and antimicrobial interventions. Because treatment failure or intolerance is common, new treatment options are needed. Daptomycin has broad Gram-positive activity, penetrates bone effectively and has bactericidal activity within biofilms. This is the first report on clinical outcomes in patients with osteomyelitis from the multicentre, retrospective, non-interventional European Cubicin(®) Outcomes Registry and Experience (EU-CORE(SM)), a large database on real-world daptomycin use. PATIENTS AND METHODS: In total, 220 patients were treated for osteomyelitis; the population was predominantly elderly, with predisposing baseline conditions such as diabetes and chronic renal/cardiac diseases. RESULTS: Most patients (76%) received prior antibiotic treatment, and first-line treatment failure was the most frequent reason to start daptomycin. Common sites of infection were the knee (22%) or hip (21%), and the most frequently isolated pathogens were Staphylococcus aureus (33%) and coagulase-negative staphylococci (32%). Overall, 52% of patients had surgery, 55% received concomitant antibiotics and 29% received a proportion of daptomycin therapy as outpatients. Clinical success was achieved in 75% of patients. Among patients with prosthetic device-related osteomyelitis, there was a trend towards higher success rates if the device was removed. Daptomycin was generally well tolerated. CONCLUSIONS: This analysis suggests that daptomycin is an effective and well-tolerated treatment option for osteomyelitis and highlights the importance of optimal surgical intervention and appropriate microbiological diagnosis for clinical outcomes.
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Antibacterianos/uso terapêutico , Daptomicina/uso terapêutico , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Osteomielite/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Bactérias Gram-Positivas/isolamento & purificação , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Osteomielite/microbiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To evaluate the stability of temocillin solution in two elastomeric infusion devices - Easypump II LT 270-27- S and Dosi-Fusor L25915-250D1 for OPAT administration during 14 days of 5°C±3°C fridge storage followed by 24 hour exposure at an in-use temperature of 32°C, when reconstituted with 0.3% citrate buffer at pH7. METHODS: Stability testing was conducted in accordance with standard protocols in the UK National Health Service Yellow Cover Document (YCD). A stability indicating assay method was applied using a high-performance liquid chromatography (HPLC) system with a photodiode array detector. Low (500 mg/240 mL), intermediate (4000 mg/240 mL) and high (6000 mg/240 mL) temocillin concentrations were tested in triplicate devices with duplicate samples taken at 11 time points during fridge storage and subsequent in-use temperature exposure. RESULT: The percentage of temocillin remaining after 14 days of fridge storage was greater than 97% in both devices and at all concentrations tested. During subsequent in-use temperature exposure, a 95% stability limit was achieved for 12 hours except for the high concentration (25 mg/mL) in the Dosi-Fusor device. It met this criterion for only 10 hours - the percent of temocillin remaining at 12 hours was 94.5%. However, for all devices and the doses tested, the degradation of temocillin was <9% at the end of 24 hours in-use temperature exposure. CONCLUSION: Temocillin reconstituted with 0.3% citrate buffer at pH7 in elastomeric infusion devices can be stored in a fridge (2°C-8°C) for 14 days meeting the YCD acceptance criteria. Considering <5% degradation, the current data supports twice daily dosing of temocillin within the OPAT setting. In jurisdictions where a <10% degradation limit is acceptable, once daily dosing with 24-hour continuous infusion may be considered. Temocillin is a useful alternative to other broad-spectrum anti-Gram-negative agents currently utilised in the OPAT setting and supports the wider antimicrobial stewardship agenda.
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Anti-Infecciosos , Medicina Estatal , Humanos , Pacientes Ambulatoriais , Citratos , Reino UnidoRESUMO
BACKGROUND: Little is known about the duration of antibiotic use in hospital settings. We evaluated the duration of hospital antibiotic therapy for four commonly prescribed antibiotics (amoxicillin, co-amoxiclav, doxycycline, and flucloxacillin) including the assessment of COVID-19 impact. METHODS: A repeated, cross-sectional study using the Hospital Electronic Prescribing and Medicines Administration system (January/2019-March/2022). Monthly median duration of therapy/duration categories was calculated, stratified by routes of administration, age, and sex. The impact of COVID-19 was assessed using segmented time-series analysis. RESULTS: There were significant variations in the median duration of therapy across routes of administration (P < 0.05), with the highest value among those antibiotic courses composed of both oral and IV antibiotics ('Both' group). Significantly higher proportions of prescriptions within the 'Both' group had a duration of >7 days compared to oral or IV. The duration of therapy differed significantly by age. Some small statistically significant changes in the level/trends of duration of therapy were observed in the post-COVID-19 period. CONCLUSIONS: No evidence for prolonged duration of therapy were observed, even during COVID-19 pandemic. The duration of IV therapy was relatively short, suggesting timely clinical review and consideration of IV to oral switch. Longer duration of therapy was observed among older patients.
Assuntos
COVID-19 , Humanos , Análise de Séries Temporais Interrompida , Estudos Transversais , Pandemias , Antibacterianos , Escócia/epidemiologia , HospitaisRESUMO
BACKGROUND: Selling antibiotics without prescriptions is mostly illegal worldwide, including in Ghana, and promotes antimicrobial resistance. We evaluated the prevalence and practice of selling antibiotics without prescriptions among community pharmacies (CPs) and drug outlets, for the first time, in Ghana to quantify and characterize this issue to inform future interventions. RESEARCH DESIGN AND METHODS: Two scenarios utilizing the Simulated Client Methodology were enacted: an upper respiratory tract infection of viral origin (scenario one); and pediatric diarrhea (scenario two). CPs/Outlets were selected by stratified proportional random sampling from four metropolitan cities (~14% of the total Ghanaian population). Selling of antibiotics was assessed at three demand levels and its overall prevalence was estimated, then stratified by the study variables. RESULTS: Out of the 265 sampled CPs/outlets, the prevalence of selling antibiotic without prescription was 88.3% (n = 234/265), with variations not only across the four regions [92.5% (n = 123/133) in Kumasi, 87.5% (n = 14/16) in Cape Coast, 84.1% (n = 69/82) in Accra, and 82.4% (n = 28/34) in Tamale] but also across CPs [90% (n = 121/134)] and drug outlets [86% (n = 113/131)]. CONCLUSIONS: A very high prevalence/sub-optimal practice of selling antibiotics without prescriptions was found. This highlights the need to increase compliance with antibiotic dispensing legislation through evidence-based interventions including education of key stakeholders.