The malignant epidemic-changing patterns of trauma

Objectives and Setting. The worldwide burden of trauma is increasing, but is unequally distributed between nations. Trauma in South Africa targets the young and productive in society and imposes a major burden on the health infrastructure. We undertook a review of injury trends among patients attending the Johannesburg Hospital Trauma Unit (JHTU) and the Johannesburg Medicolegal Laboratory (JMLL) in order to document the evolution in patterns of trauma over a 17-year period of great social and political change. Design, subjects and outcome measures. This was a retrospective review of all priority-one patients attending the JHTU from January 1985 to December 2001. The JHTU trauma database was used to retrieve information on patient demographics, wound mechanism and injury severity. The database at the JMLL, maintained since 1996, was examined and the manner and place of death were analysed.Results. The JHTU has seen an unprecedented increase in the number of trauma patients over the last 17 years. The patients' demographic profiles have altered and injury is now predominantly due to interpersonal violence. Unnatural deaths examined at the JMLL have declined by 19% since 1996; however, the proportion of those deaths due to gunshot wounds has risen.Conclusions. The social and political changes in South Africa in recent years have led to changes in the injury profiles seen at the JHTU. Part of the increase can be explained by desegregation and a reduction in the provision of local hospital services; however, the impact of urbanisation within South Africa, cross-border migration and the high incidence of substance abuse are recognised. Evidence supports the implementation of legislative, environmental, social and behavioural interventions to contain and reduce the incidence and impact of violence and injury. Concerted efforts must be made at all levels to curb South Africa's  trauma  epidemic

Guideline: Appropriate use of tigecycline

INTRODUCTION: Tigecycline, the first of a new class of antibiotics, the glycylcyclines, was licensed in South Africa for the parenteral treatment of adult patients with complicated intraabdominal infections (cIAIs) and complicated skin and softtissue infections (cSSTIs). METHODS: A multidisciplinary meeting representative of the Association of Surgeons of South Africa, the Critical Care Society of Southern Africa, the Federation of Infectious Diseases Societies of Southern Africa, the South African Thoracic Society and the Trauma Society of South Africa was held to draw up a national guideline for the appropriate use of tigecycline. Background information reviewed included randomised controlled trials, other relevant publications and local antibiotic susceptibility patterns. The initial document was drafted at the meeting. Subsequent drafts were circulated to members of the working group for modification. OUTPUT: The guideline addresses several important aspects of the new agent, summarising key clinical data and highlighting important considerations with the use of the drug. The recommendations in this guideline are based on currently available scientific evidence together with the consensus opinion of the authors. CONCLUSION: This statement was written out of concern regarding the widespread misuse of antibiotics. Its primary intention is to facilitate heterogeneous use of antibiotics as a component of antibiotic stewardship and to highlight the appropriate use of tigecycline in particular.Sponsored through an unrestricted educational grant from Wyeth

Recombinant activated factor VII as an adjunctive therapy for bleeding control in severe trauma patients with coagulopathy: subgroup analysis from two randomized trials

INTRODUCTION: We conducted a post-hoc analysis on the effect of recombinant factor VIIa (rFVIIa) on coagulopathic patients from two randomized, placebo-controlled, double-blind trials of rFVIIa as an adjunctive therapy for bleeding in patients with severe trauma. METHODS: Blunt and penetrating trauma patients were randomly assigned to rFVIIa (200 + 100 + 100 μg/kg) at 0, 1, and 3 hours after transfusion of 8 units of red blood cells (RBCs) or to placebo. Subjects were monitored for 48 hours post-dosing and followed for 30 days. Coagulopathy was retrospectively defined as transfusion of fresh frozen plasma (FFP) (>1 unit of FFP per 4 units of RBCs), FFP in addition to whole blood, and transfusion of platelets and/or cryoprecipitate. RESULTS: Sixty rFVIIa-treated and 76 placebo subjects were retrospectively identified as being coagulopathic. No significant differences were noted in baseline characteristics. The rFVIIa-treated coagulopathic subgroup consumed significantly less blood product: RBC transfusion decreased by 2.6 units for the whole study population (P = 0.02) and by 3.5 units among patients surviving more than 48 hours (P < 0.001). Transfusion of FFP (1,400 versus 660 ml, P < 0.01), platelet (300 versus 100 ml, P = 0.01), and massive transfusions (29% versus 6%, P < 0.01) also dropped significantly. rFVIIa reduced multi-organ failure and/or acute respiratory distress syndrome in the coagulopathic patients (3% versus 20%, P = 0.004), whereas thromboembolic events were equally present in both groups (3% versus 4%, P = 1.00). CONCLUSION: Coagulopathic trauma patients appear to derive particular benefit from early adjunctive rFVIIa therapy

Guideline summary : appropriate use of tigecycline

Tigecycline, the first of a new class of broad-spectrum antibiotics (the glycylcyclines), has been licensed in South Africa for the parenteral treatment of adult patients with complicated intra-abdominal infections (cIAIs) and complicated skin and soft-tissue infections (cSSTIs).http://www.hmpg.co.za/journaldetail.php?journalno=

Pharmacokinetics of recombinant activated factor VII in trauma patients with severe bleeding

INTRODUCTION: Recombinant activated factor VII (rFVIIa) has been used as adjunctive therapy in trauma patients with severe bleeding. However, its pharmacokinetics profile remains unknown. METHODS: In two placebo-controlled studies in patients with blunt and penetrating trauma, the pharmacokinetics of rFVIIa given at an initial dose of 200 μg.kg(-1 )after transfusion of eight red blood cell units, followed by additional doses of 100 μg.kg(-1), one and three hours later, have been studied, based on the FVII coagulant activity assay. Both non-compartment and population pharmacokinetic analyses were performed. A two-compartment, population pharmacokinetic model was used to estimate a population profile for the rFVIIa dosing regimen. Data are population means (percent coefficient of variation (CV)). RESULTS: Based on the two-compartment population model, the estimated pharmacokinetic parameters were: clearance 40 (30% CV) ml.kg(-1).h(-1); central volume of distribution 89 (32% CV) ml.kg(-1); inter-compartmental clearance 24 ml.kg(-1).h(-1); and peripheral compartment volume 31 ml.kg(-1). Baseline FVII coagulant activity was estimated at 0.29 (39% CV) U.ml(-1), initial half-life was 0.6 (34% CV) hours, and terminal half-life 2.4 (50% CV) hours. High intra- and inter-patient variability was noted in volume of distribution and clearance, which was in part correlated with the transfusion requirements as the single significant covariate. The non-compartmental analysis led to almost identical estimates of key parameters. CONCLUSION: A high intra- and inter-patient variability was noted in the volume of distribution and clearance of rFVIIa in trauma patients with severe bleeding, mainly related with the transfusion requirements and thus blood loss and/or bleeding rate

Clinical efficacy and safety of a novel antifungal, Fosmanogepix, in patients with candidemia caused by Candida auris : results from a Phase 2 trial

DATA AVAILABILITY: Upon request, and subject to review, Pfizer will provide the data that support the findings of this study. Subject to certain criteria, conditions and exceptions, Pfizer may also provide access to the related individual de-identified participant data. See https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information.Fosmanogepix (FMGX), a novel antifungal available in intravenous (IV) and oral formulations, has broad-spectrum activity against pathogenic yeasts and molds, including fungi resistant to standard of care antifungals. This multicenter, open-label, single-arm study evaluated FMGX safety and efficacy for treatment of candidemia and/or invasive candidiasis caused by Candida auris. Eligible participants were ≥18 years, with established candidemia and/or invasive candidiasis caused by C. auris, (cultured within 120 h [for candidemia] or 168 h [for invasive candidiasis without candidemia] with accompanying clinical signs) and limited treatment options. Participants were treated with FMGX (≤42 days; loading dose: 1000 mg IV twice daily [Day 1], followed by 600 mg IV once daily [QD]). Switching to oral FMGX 800 mg QD was permitted from Day 4. Primary endpoint was treatment success (survival and clearance of C. auris from blood/tissue cultures without additional antifungals) at the end of the study treatment (EOST), assessed by an independent data review committee (DRC). Day 30 survival was a secondary endpoint. In vitro susceptibility of Candida isolates was assessed. Nine participants with candidemia (male:6, female:3; 21 to 76 years) in intensive care units in South Africa were enrolled; all received IV FMGX only. DRC-assessed treatment success at EOST and Day 30 survival were 89% (8/9). No treatment related adverse events or study drug discontinuations were reported. FMGX demonstrated potent in vitro activity against all C. auris isolates (MIC range: 0.008 to 0.015 μg/mL [CLSI]; 0.004–0.03 μg/mL [EUCAST]), with the lowest MICs compared to other antifungals tested. Thus, the results showed that FMGX was safe, well-tolerated, and efficacious in participants with candidemia caused by C. auris.Amplyx, a subsidiary of Pfizer Inc.https://journals.asm.org/journal/aacCritical Car

Antimicrobial susceptibility of gram-negative pathogens isolated from patients with complicated intra-abdominal infections in South African hospitals (SMART Study 2004-2009) : impact of the new carbapenem breakpoints

BACKGROUND: The Study for Monitoring Antimicrobial Resistance Trends (SMART) follows trends in resistance among aerobic and facultative anaerobic gram-negative bacilli (GNB) isolated from complicated intra-abdominal infections (cIAIs) in patients around the world. METHODS: During 2004–2009, three centralized clinical microbiology laboratories serving 59 private hospitals in three large South African cities collected 1,218 GNB from complicated intra-abdominal infections (cIAIs) and tested them for susceptibility to 12 antibiotics according to the 2011 Clinical Laboratory Standards Institute (CLSI) guidelines. RESULTS: Enterobacteriaceae comprised 83.7% of the isolates. Escherichia coli was the species isolated most commonly (46.4%), and 7.6% of these were extended-spectrum b-lactamase (ESBL)-positive. The highest ESBL rate was documented for Klebsiella pneumoniae (41.2%). Overall, ertapenem was the antibiotic most active against susceptible species for which it has breakpoints (94.6%) followed by amikacin (91.9%), piperacillin-tazobactam (89.3%), and imipenem-cilastatin (87.1%), whereas rates of resistance to ceftriaxone, cefotaxime, ciprofloxacin, and levofloxacin were documented to be 29.7%, 28.7%, 22.5%, and 21.1%, respectively. Multi-drug resistance (MDR), defined as resistance to three or more antibiotic classes, was significantly more common in K. pneumoniae (27.9%) than in E. coli (4.9%; p < 0.0001) or Proteus mirabilis (4.1%; p < 0.05). Applying the new CLSI breakpoints for carbapenems, susceptibility to ertapenem was reduced significantly in ESBL-positive E. coli compared with ESBL-negative isolates (91% vs. 98%; p < 0.05), but this did not apply to imipenem-cilastatin (95% vs. 99%; p = 0.0928). A large disparity between imipenem-cilastatin and ertapenem susceptibility in P. mirabilis and Morganella morganii was documented (24% vs. 96% and 15% vs. 92%, respectively), as most isolates of these two species had imipenem-cilastatin minimum inhibitory concentrations in the 2–4 mcg/mL range, which is no longer regarded as susceptible. CONCLUSIONS: This study documented substantial resistance to standard antimicrobial therapy among GNB commonly isolated from cIAIs in South Africa. With the application of the new CLSI carbapenem breakpoints, discrepancies were noted between ertapenem and imipenem-cilastatin with regard to the changes in their individual susceptibilities. Longitudinal surveillance of susceptibility patterns is useful to guide recommendations for empiric antibiotic use in cIAIs.Merck & Co., Inc.http://www.liebertpub.com/overview/surgical-infections/53/am2013ay201

Severe traumatic injury during long duration spaceflight: Light years beyond ATLS

Traumatic injury strikes unexpectedly among the healthiest members of the human population, and has been an inevitable companion of exploration throughout history. In space flight beyond the Earth's orbit, NASA considers trauma to be the highest level of concern regarding the probable incidence versus impact on mission and health. Because of limited resources, medical care will have to focus on the conditions most likely to occur, as well as those with the most significant impact on the crew and mission. Although the relative risk of disabling injuries is significantly higher than traumatic deaths on earth, either issue would have catastrophic implications during space flight. As a result this review focuses on serious life-threatening injuries during space flight as determined by a NASA consensus conference attended by experts in all aspects of injury and space flight

2013 WSES guidelines for management of intra-abdominal infections

Peer reviewe