ABSTRACT
BACKGROUND: In vitro laboratory and animal studies demonstrate a synergistic role for the combination of vancomycin and antistaphylococcal ß-lactams for methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Prospective clinical data are lacking. METHODS: In this open-label, multicenter, clinical trial, adults with MRSA bacteremia received vancomycin 1.5 g intravenously twice daily and were randomly assigned (1:1) to receive intravenous flucloxacillin 2 g every 6 hours for 7 days (combination group) or no additional therapy (standard therapy group). Participants were stratified by hospital and randomized in permuted blocks of variable size. Randomization codes were kept in sealed, sequentially numbered, opaque envelopes. The primary outcome was the duration of MRSA bacteremia in days. RESULTS: We randomly assigned 60 patients to receive vancomycin (n = 29), or vancomycin plus flucloxacillin (n = 31). The mean duration of bacteremia was 3.00 days in the standard therapy group and 1.94 days in the combination group. According to a negative binomial model, the mean time to resolution of bacteremia in the combination group was 65% (95% confidence interval, 41%-102%; P = .06) that in the standard therapy group. There was no difference in the secondary end points of 28- and 90-day mortality, metastatic infection, nephrotoxicity, or hepatotoxicity. CONCLUSIONS: Combining an antistaphylococcal ß-lactam with vancomycin may shorten the duration of MRSA bacteremia. Further trials with a larger sample size and objective clinically relevant end points are warranted. Australian New Zealand Clinical Trials Registry: ACTRN12610000940077 (www.anzctr.org.au).
Subject(s)
Anti-Bacterial Agents/pharmacology , Bacteremia/drug therapy , Floxacillin/pharmacology , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Staphylococcal Infections/drug therapy , Vancomycin/pharmacology , Administration, Intravenous , Adolescent , Adult , Aged , Aged, 80 and over , Animals , Bacteremia/microbiology , Drug Therapy, Combination/methods , Female , Humans , Male , Middle Aged , New Zealand , Prospective Studies , Staphylococcal Infections/microbiology , Time Factors , Treatment Outcome , Young AdultABSTRACT
Enterococci are a major cause of health care-associated infections and account for approximately 10% of all bacteremias globally. The aim of this study was to determine the proportion of enterococcal bacteremia isolates in Australia that are antimicrobial resistant, with particular emphasis on susceptibility to ampicillin and the glycopeptides, and to characterize the molecular epidemiology of the Enterococcus faecalis and Enterococcus faecium isolates. From 1 January to 31 December 2011, 1,079 unique episodes of bacteremia were investigated, of which 95.8% were caused by either E. faecalis (61.0%) or E. faecium (34.8%). The majority of bacteremias were health care associated, and approximately one-third were polymicrobial. Ampicillin resistance was detected in 90.4% of E. faecium isolates but was not detected in E. faecalis isolates. Vancomycin nonsusceptibility was reported in 0.6% and 36.5% of E. faecalis and E. faecium isolates, respectively. Unlike Europe and the United States, where vancomycin resistance in E. faecium is predominately due to the acquisition of the vanA operon, 98.4% of E. faecium isolates harboring van genes carried the vanB operon, and 16.1% of the vanB E. faecium isolates had vancomycin MICs at or below the susceptible breakpoint of the CLSI. Although molecular typing identified 126 E. faecalis pulsed-field gel electrophoresis pulsotypes, >50% belonged to two pulsotypes that were isolated across Australia. E. faecium consisted of 73 pulsotypes from which 43 multilocus sequence types were identified. Almost 90% of the E. faecium isolates were identified as CC17 clones, of which approximately half were characterized as ST203, which was isolated Australia-wide. In conclusion, the Australian Enterococcal Sepsis Outcome Programme (AESOP) study has shown that although they are polyclonal, enterococcal bacteremias in Australia are frequently caused by ampicillin-resistant vanB E. faecium.
Subject(s)
Bacteremia/epidemiology , Enterococcus faecalis/isolation & purification , Enterococcus faecium/isolation & purification , Gram-Positive Bacterial Infections/epidemiology , Anti-Bacterial Agents/pharmacology , Australia/epidemiology , Bacteremia/microbiology , Coinfection/epidemiology , Coinfection/microbiology , Cross Infection/epidemiology , Cross Infection/microbiology , Drug Resistance, Bacterial , Enterococcus faecalis/classification , Enterococcus faecalis/genetics , Enterococcus faecium/classification , Enterococcus faecium/genetics , Genes, Bacterial , Gram-Positive Bacterial Infections/microbiology , Humans , Microbial Sensitivity Tests , Molecular Epidemiology , Molecular TypingABSTRACT
INTRODUCTION: Emergency department (ED) flow impacts patient safety, quality of care and ED provider satisfaction. Throughput interventions have been shown to improve flow, yet few studies have reported the impact of ED physician leadership roles on patient flow and provider experiences. The study objective was to evaluate the impacts of the emergency physician lead role on ED flow metrics and provider experiences. METHODS: Quantitative data about patient flow metrics were collected from ED information systems in two tertiary hospital EDs and analyzed to compare ED length of stay, EMS hallway length of stay, physician initial assessment time, 72-h readmission and left without being seen rates three months before and following emergency physician lead role implementation. ED flow metrics for adult patients at each site were analyzed independently using descriptive and inferential statistics, t tests and multivariable regression analysis. Qualitative data were collected via surveys from ED providers (physicians, nurses, and EMS) about their experiences working with the emergency physician leads and analyzed for themes about emergency physician leads impact. RESULTS: The number of ED visits was relatively stable pre-post at the Peter Lougheed Centre (Lougheed) but increased pre-post at the Foothills Medical Centre (Foothills). Post-intervention at Lougheed median ED length of stay decreased by 18 min (p < 0.001) and at Foothills ED length of stay increased by 8 min (p < 0.001). EMS length of stay at Lougheed decreased by 20 min (p < 0.001), and at Foothills length of stay increased by 17 min (p < 0.001). Themes in provider feedback were that emergency physician leads (1) facilitated patient flow, (2) impacted provider workload, and (3) supported patient flow and safety with early assessments, treatments and investigations. CONCLUSION: In this study, the emergency physician lead impacted ED flow metrics variably at different sites, but important learnings from provider experiences can guide future emergency physician lead implementation.
RéSUMé: INTRODUCTION: Le flux des services d'urgence a une incidence sur la sécurité des patients, la qualité des soins et la satisfaction des fournisseurs de services d'urgence. Il a été démontré que les interventions de débit améliorent le flux, mais peu d'études ont rapporté l'impact des rôles de leadership des médecins des urgences sur le flux des patients et les expériences des prestataires. L'objectif de l'étude était d'évaluer l'impact du rôle du médecin chef des urgences sur les paramètres de flux des urgences et les expériences des prestataires. MéTHODES: Les données quantitatives sur les paramètres du flux des patients ont été recueillies à partir des systèmes d'information des urgences de deux hôpitaux tertiaires et analysées afin de comparer la durée du séjour aux urgences, la durée du séjour dans le couloir des SMU, le temps d'évaluation initiale par le médecin, les réadmissions dans les 72 heures et les taux de sortie sans consultation trois mois avant et après la mise en Åuvre du rôle de chef des urgences. Les paramètres de débit des urgences pour les patients adultes de chaque site ont été analysés indépendamment à l'aide de statistiques descriptives et inférentielles, de tests t et d'une analyse de régression multivariable. Les données qualitatives ont été recueillies par le biais d'enquêtes auprès de fournisseurs de services d'urgence (médecins, infirmières et services médicaux d'urgence) sur leur expérience de travail avec les médecins chefs des services d'urgence et analysées pour en dégager les thèmes concernant l'impact des médecins chefs des services d'urgence. RéSULTATS: Le nombre de visites aux urgences était relativement stable avant et après au Peter Lougheed Centre (Lougheed), mais a augmenté avant et après au Foothills Medical Center (Foothills). Après l'intervention, la durée médiane du séjour aux urgences de Lougheed a diminué de 18 minutes (p < 0.001) et celle des urgences de Foothills a augmenté de 8 minutes (p < 0.001). La durée du séjour en SMU a diminué de 20 minutes à Lougheed (p < 0.001), et a augmenté de 17 minutes à Foothills (p < 0.001). Les thèmes abordés dans les commentaires des fournisseurs étaient les suivants : les responsables des urgences (1) facilitaient le flux des patients, (2) avaient un impact sur la charge de travail des fournisseurs et (3) favorisaient le flux et la sécurité des patients grâce à des évaluations, des traitements et des examens précoces. CONCLUSION: Dans cette étude, le médecin chef des urgences a eu un impact variable sur les paramètres de débit des urgences dans les différents sites, mais les enseignements importants tirés des expériences des fournisseurs peuvent guider la mise en Åuvre future du médecin chef des urgences.
Subject(s)
Emergency Service, Hospital , Physicians , Adult , Humans , Length of Stay , Workload , Hospitals , Retrospective StudiesABSTRACT
BACKGROUND: In Haiti, cardiovascular disease is a leading cause of morbidity and mortality, with congenital and rheumatic heart disease comprising a large portion of disease burden. However, domestic disparities in cardiac care access and their impact on clinical outcomes remain poorly understood. We analyzed population-level sociodemographic variables to predict cardiac care outcomes across the 10 Haitian administrative departments. METHODS: This cross-sectional study combined data from a 2016-17 Haitian national survey with aggregate outcomes from the Haiti Cardiac Alliance (HCA) database (n = 1817 patients). Using univariate and multivariable regression analyses, the proportion of HCA patients belonging to each of three clinical categories (active treatment, lost to follow-up, deceased preoperatively) was modeled in relation to six population-level variables selected from national survey data at the level of the administrative department. RESULTS: In univariate analysis, higher department rates of childhood growth retardation were associated with a lower proportion of patients in active care (OR = 0.979 [0.969, 0.989], p = 0.002) and a higher proportion of patients lost to follow-up (OR = 1.016 [1.006, 1.026], p = 0.009). In multivariable analysis, the proportion of department patients in active care was inversely associated with qualified prenatal care (OR = 0.980 [0.971, 0.989], p = 0.005), and child growth retardation (OR = 0.977 [0.972, 0.983]), p = 0.00019). Similar multivariable results were obtained for department rates of loss to follow-up (child growth retardation: OR = 1.018 [1.011, 1.025], p = 0.002; time to nearest healthcare facility in an emergency: OR = 1.004 [1.000, 1.008, p = 0.065) and for preoperative mortality (prenatal care: OR = 0.989 [0.981, 0.997], p = 0.037; economic index: OR = 0.996 [0.995, 0.998], p = 0.007; time to nearest healthcare facility in an emergency: OR = 0.992 [0.988, 0.996], p = 0.0046). CONCLUSIONS: Population-level survey data on multiple variables predicted domestic disparities in HCA clinical outcomes by region. These findings may help to identify underserved areas in Haiti, where increased cardiac care resources are required to improve health equity. This approach to analyzing clinical outcomes through the lens of population-level survey data may inform future health policies and interventions designed to increase cardiac care access in Haiti and other low-income countries.
Subject(s)
Health Facilities , Population Health , Child , Female , Pregnancy , Humans , Haiti/epidemiology , Cross-Sectional Studies , Growth DisordersABSTRACT
BACKGROUND: Peri-prosthetic joint infection (PJI) is a devastating complication of joint replacement surgery. Determining the optimal duration of intravenous (IV) antibiotics for PJI managed with debridement and implant retention (DAIR) is a research priority. METHODS: Patients undergoing DAIR for early and late-acute PJI of the hip or knee were randomised to receive 2 (short-course) or 6 (standard-course) weeks of IV antibiotics, with both groups completing 12 weeks of antibiotics in total. The primary endpoint of this pilot, open-label, randomised trial was a 7-point ordinal desirability of outcome ranking (DOOR) score, which accounted for mortality, clinical cure and treatment adverse events at 12 months. Duration of IV treatment was used as a tiebreaker, with shorter courses ranked higher. Outcome adjudication was performed by expert clinicians blinded to the allocated intervention (Australia and New Zealand Clinical Trials Registry ACTRN12617000127303). RESULTS: 60 patients were recruited; 31 and 29 were allocated to short- and standard-course treatment, respectively. All had an evaluable outcome at 12 months and were analysed by intention-to-treat. Clinical cure was demonstrated in 44 (73%) overall; 22 (71%) in the short-course group and 22 (76%) in the standard-care group (P=0.77). Using the DOOR approach, the probability that short- was better than standard-course treatment was 59.7% (95% confidence interval 45.1-74.3). CONCLUSIONS: In selected patients with early and late-acute PJI managed with DAIR, shorter courses of IV antibiotics may be appropriate. Due to small sample size, these data accord with, but do not confirm, results from other international trials of early transition to oral antibiotics.
Subject(s)
Arthritis, Infectious , Prosthesis-Related Infections , Anti-Bacterial Agents/therapeutic use , Arthritis, Infectious/drug therapy , Arthritis, Infectious/surgery , Debridement/methods , Humans , Pilot Projects , Prosthesis-Related Infections/drug therapy , Prosthesis-Related Infections/surgery , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND: To provide an estimate of the population at risk for late complications of arthroplasty, we aimed to determine the prevalence of Australians living with one or more joint replacements. METHODS: Data included all arthroplasty procedures performed in Australia from 2003 to 2016 recorded by the Australian Orthopaedic Association National Joint Replacement Registry. The age- and gender-specific Australian population was obtained from the Australian Bureau of Statistics and used as denominator data. Survival data for each joint replacement, and of individuals, were used to estimate the arthroplasty prevalence. Analyses by age, gender and joint replacement site were undertaken. Prevalence estimates were augmented with procedural data captured before 2003 modelled with assumptions accounting for age and gender distributions, overall survival and arthroplasty revision rates. RESULTS: By the end of 2016, there were 824 769 Australians living with at least one joint replacement, representing 3.4% of the total population. The prevalence of joint replacement is increasing in all age groups, but was highest amongst older Australians, with an overall prevalence of 22.5%, and 13.3% in those aged >85 years and 65-84 years, respectively. The prevalence of people living with multiple joint replacements is increasing more rapidly than patients who have undergone only one joint replacement procedure. CONCLUSION: The prevalence of older Australians living with joint replacements is rapidly increasing, providing an estimate of the population-at-risk for late complications of arthroplasty including peri-prosthetic infection and fracture.
Subject(s)
Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , Aged , Aged, 80 and over , Australia/epidemiology , Humans , Prevalence , Registries , Reoperation , Risk FactorsABSTRACT
BACKGROUND: Exotoxins are important virulence factors in Staphylococcus aureus. Clindamycin, a protein synthesis inhibitor antibiotic, is thought to limit exotoxin production and improve outcomes in severe S. aureus infections. However, randomised prospective data to support this are lacking. METHODS: An open-label, multicentre, randomised controlled trial (RCT) will compare outcome differences in severe S. aureus infection between standard treatment (flucloxacillin/cefazolin in methicillin-susceptible S. aureus; and vancomycin/daptomycin in methicillin-resistant S. aureus) and standard treatment plus an additional clindamycin given for 7 days. We will include a minimum of 60 participants (both adult and children) in the pilot study. Participants will be enrolled within 72 h of an index culture. Severe infections will include septic shock, necrotising pneumonia, or multifocal and non-contiguous skin and soft tissue/osteoarticular infections. Individuals who are immunosuppressed, moribund, with current severe diarrhoea or Clostridiodes difficile infection, pregnant, and those with anaphylaxis to ß-lactams or lincosamides will be excluded. The primary outcomes measure is the number of days alive and free (1 or 0) of systemic inflammatory response syndrome (SIRS) within the first 14 days post randomisation. The secondary outcomes measure will include all-cause mortality at 14, 42, and 90 days, time to resolution of SIRS, proportion with microbiological treatment failure, and rate of change of C-reactive protein over time. Impacts of inducible clindamycin resistance, strain types, methicillin susceptibility, and presence of various exotoxins will also be analysed. DISCUSSION: This study will assess the effect of adjunctive clindamycin on patient-centred outcomes in severe, toxin-mediated S. aureus infections. The pilot study will provide feasibility for a much larger RCT. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12617001416381p . Registered on 6 October 2017.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Clindamycin/therapeutic use , Randomized Controlled Trials as Topic , Staphylococcal Infections/drug therapy , Adolescent , Adult , C-Reactive Protein/analysis , Child , Child, Preschool , Clindamycin/adverse effects , Humans , Infant , Outcome Assessment, Health Care , Pilot Projects , Research DesignABSTRACT
Background: There are few epidemiological data available to inform a national response to community-acquired methicillin-resistant Staphylococcus aureus (MRSA) in Papua New Guinea (PNG). Methods: We performed a cross-sectional survey to determine the pattern of MRSA nasal colonization and the diversity of circulating MRSA clones among adults and adolescents in Madang Province, PNG. Results: S. aureus nasal colonization was confirmed in 44 (17.1%) of 257 participants. Four (9.1%) isolates were methicillin resistant. Resistance to other antimicrobial agents was uncommon. Detailed molecular typing of three MRSA isolates demonstrated multiple MRSA clones in this community, of which two carried the Panton-Valentin leukocidin-associated virulence genes. Conclusions: MRSA is likely to account for a clinically important proportion of staphylococcal disease in PNG. There are multiple MRSA clones in PNG. Ongoing surveillance of community and invasive isolates is a critical component of an effective response to the challenge of community-acquired MRSA in this and many other resource-limited contexts.