Aminoglycosides for Intra-Abdominal Infection: Equal to the Challenge?

Background: Aminoglycosides, combined with antianaerobic agents, have been used widely for the treatment of intra-abdominal infection. However, some prospective randomized controlled trials and other data suggested that aminoglycosides were less efficacious than newer comparators for the treatment of these infections. We therefore performed a meta-analysis of all prospective randomized controlled trials utilizing aminoglycosides to reevaluate the efficacy of these agents for the treatment of intra-abdominal infection. Methods: Published English-language prospective randomized controlled trials comparing aminoglycosides with other agents for treatment of intra-abdominal infection were identified by MEDLINE search. For each study, data were collected regarding the number of patients enrolled and evaluated, their basic demographic characteristics, the sources of the intra-abdominal infections, the number of failures as determined by the study investigators, quality score, and the use of serum drug concentrations to monitor aminoglycoside therapy. These data were combined to calculate odds ratios for risk of therapeutic failure, which were assessed for significance using Chi-square analysis. Results: Forty-seven prospective randomized controlled trials comparing aminoglycosides to other agents were identified. These were published between 1981 and 2000, and included a total of 5,182 evaluable patients. Analysis of all studies combined revealed an odds ratio that slightly, but significantly, favored the comparators. After excluding six trials using comparators that lacked accepted antianaerobic efficacy, the odds ratio more strongly favored comparators. Trials published since 1990 also notably favored comparators. Analyzing results by quality score or the use of aminoglycoside monitoring did not alter these findings. Conclusions: In this meta-analysis, aminoglycosides were less efficacious than newer comparators for the treatment of intra-abdominal infection. Given the well-known toxicities of these agents, we conclude that they should not be used as first-line therapy for these infections

The Surgical Infection Society Guidelines on Antimicrobial Therapy for Intra-Abdominal Infections: Evidence for the Recommendations

Revised guidelines for the use of antimicrobial therapy in patients with intra-abdominal infections were recently developed by the Therapeutic Agents Committee of the Surgical Infection Society (Mazuski et al., Surg Infect2002;3:161-173). These were based, insofar as possible, on evidence published over the past decade. The objective of this document is to describe the process by which the Committee identified and reviewed the published literature utilized to develop the recommendations and to summarize the results of those reviews. English-language articles published between 1990 and 2000 related to antimicrobial therapy for intra-abdominal infections were identified by a systematic MEDLINE search and an examination of references included in recent review articles. If current literature with regard to a specific issue was lacking, relevant articles published prior to 1990 were identified. All prospective randomized controlled trials, as well as other articles selected by the Committee, were evaluated individually and collectively. Data with regard to patient numbers, types of infections, and results of interventions were abstracted. Studies were categorized according to their design, and all included trials were graded according to quality. On the basis of this evidence, the Committee formulated recommendations for antimicrobial therapy for intra-abdominal infections and graded those recommendations. After receiving comments from invited reviewers and the general membership of the Society, the guidelines were finalized and submitted to the Council of the Surgical Infection Society for approval. The final recommendations related to the selection of patients needing therapeutic antimicrobials, acceptable antimicrobial regimens, duration of antimicrobial use, and the identification and treatment of higher-risk patients. Although numerous publications pertaining to these topics were identified, but nearly all of the prospective randomized controlled trials represented comparisons of different antimicrobial regimens for the treatment of intra-abdominal infections. A few prospective trials evaluated the need for therapeutic antimicrobial therapy in patients with peritoneal contamination following abdominal trauma. The quality of these prospective trials was highly variable. Many did not limit enrollment to patients with complicated intra-abdominal infections, lacked blinding of treatment assignment, did not provide a complete description of the criteria used to determine therapeutic success or failure, failed to identify the reasons why patients were excluded from analysis, or did not include an intention-to-treat analysis. For many issues, no prospective randomized controlled trials were encountered, and guidelines had to be formulated using evidence from studies with historical controls or uncontrolled data, or on the basis of expert opinion

Comparison of Mortality Following Hospitalisation for Isolated Head Injury in England and Wales, and Victoria, Australia

BACKGROUND: Traumatic brain injury (TBI) remains a leading cause of death and disability. The National Institute for Health and Clinical Excellence (NICE) guidelines recommend transfer of severe TBI cases to neurosurgical centres, irrespective of the need for neurosurgery. This observational study investigated the risk-adjusted mortality of isolated TBI admissions in England/Wales, and Victoria, Australia, and the impact of neurosurgical centre management on outcomes. METHODS: Isolated TBI admissions (>15 years, July 2005-June 2006) were extracted from the hospital discharge datasets for both jurisdictions. Severe isolated TBI (AIS severity >3) admissions were provided by the Trauma Audit and Research Network (TARN) and Victorian State Trauma Registry (VSTR) for England/Wales, and Victoria, respectively. Multivariable logistic regression was used to compare risk-adjusted mortality between jurisdictions. FINDINGS: Mortality was 12% (749/6256) in England/Wales and 9% (91/1048) in Victoria for isolated TBI admissions. Adjusted odds of death in England/Wales were higher compared to Victoria overall (OR 2.0, 95% CI: 1.6, 2.5), and for cases <65 years (OR 2.36, 95% CI: 1.51, 3.69). For severe TBI, mortality was 23% (133/575) for TARN and 20% (68/346) for VSTR, with 72% of TARN and 86% of VSTR cases managed at a neurosurgical centre. The adjusted mortality odds for severe TBI cases in TARN were higher compared to the VSTR (OR 1.45, 95% CI: 0.96, 2.19), but particularly for cases <65 years (OR 2.04, 95% CI: 1.07, 3.90). Neurosurgical centre management modified the effect overall (OR 1.12, 95% CI: 0.73, 1.74) and for cases <65 years (OR 1.53, 95% CI: 0.77, 3.03). CONCLUSION: The risk-adjusted odds of mortality for all isolated TBI admissions, and severe TBI cases, were higher in England/Wales when compared to Victoria. The lower percentage of cases managed at neurosurgical centres in England and Wales was an explanatory factor, supporting the changes made to the NICE guidelines

Long-term health status and trajectories of seriously injured patients: A population-based longitudinal study

Improved understanding of the quality of survival of patients is crucial in evaluating trauma care, understanding recovery patterns and timeframes, and informing healthcare, social, and disability service provision. We aimed to describe the longer-term health status of seriously injured patients, identify predictors of outcome, and establish recovery trajectories by population characteristics.A population-based, prospective cohort study using the Victorian State Trauma Registry (VSTR) was undertaken. We followed up 2,757 adult patients, injured between July 2011 and June 2012, through deaths registry linkage and telephone interview at 6-, 12-, 24-, and 36-months postinjury. The 3-level EuroQol 5 dimensions questionnaire (EQ-5D-3L) was collected, and mixed-effects regression modelling was used to identify predictors of outcome, and recovery trajectories, for the EQ-5D-3L items and summary score. Mean (SD) age of participants was 50.8 (21.6) years, and 72% were male. Twelve percent (n = 333) died during their hospital stay, 8.1% (n = 222) of patients died postdischarge, and 155 (7.0%) were known to have survived to 36-months postinjury but were lost to follow-up at all time points. The prevalence of reporting problems at 36-months postinjury was 37% for mobility, 21% for self-care, 47% for usual activities, 50% for pain/discomfort, and 41% for anxiety/depression. Continued improvement to 36-months postinjury was only present for the usual activities item; the adjusted relative risk (ARR) of reporting problems decreased from 6 to 12 (ARR 0.87, 95% CI: 0.83-0.90), 12 to 24 (ARR 0.94, 95% CI: 0.90-0.98), and 24 to 36 months (ARR 0.95, 95% CI: 0.95-0.99). The risk of reporting problems with pain or discomfort increased from 24- to 36-months postinjury (ARR 1.06, 95% CI: 1.01, 1.12). While loss to follow-up was low, there was responder bias with patients injured in intentional events, younger, and less seriously injured patients less likely to participate; therefore, these patient subgroups were underrepresented in the study findings.The prevalence of ongoing problems at 3-years postinjury is high, confirming that serious injury is frequently a chronic disorder. These findings have implications for trauma system design. Investment in interventions to reduce the longer-term impact of injuries is needed, and greater investment in primary prevention is needed

The Surgical Infection Society revised guidelines on the management of intra-abdominal infection

Background: Previous evidence-based guidelines on the management of intra-abdominal infection (IAI) were published by the Surgical Infection Society (SIS) in 1992, 2002, and 2010. At the time the most recent guideline was released, the plan was to update the guideline every five years to ensure the timeliness and appropriateness of the recommendations. Methods: Based on the previous guidelines, the task force outlined a number of topics related to the treatment of patients with IAI and then developed key questions on these various topics. All questions were approached using general and specific literature searches, focusing on articles and other information published since 2008. These publications and additional materials published before 2008 were reviewed by the task force as a whole or by individual subgroups as to relevance to individual questions. Recommendations were developed by a process of iterative consensus, with all task force members voting to accept or reject each recommendation. Grading was based on the GRADE (Grades of Recommendation Assessment, Development, and Evaluation) system; the quality of the evidence was graded as high, moderate, or weak, and the strength of the recommendation was graded as strong or weak. Review of the document was performed by members of the SIS who were not on the task force. After responses were made to all critiques, the document was approved as an official guideline of the SIS by the Executive Council. Results: This guideline summarizes the current recommendations developed by the task force on the treatment of patients who have IAI. Evidence-based recommendations have been made regarding risk assessment in individual patients; source control; the timing, selection, and duration of antimicrobial therapy; and suggested approaches to patients who fail initial therapy. Additional recommendations related to the treatment of pediatric patients with IAI have been included. Summary: The current recommendations of the SIS regarding the treatment of patients with IAI are provided in this guideline

Estimating Long-Term Survival of Critically Ill Patients: The PREDICT Model

BACKGROUND: Long-term survival outcome of critically ill patients is important in assessing effectiveness of new treatments and making treatment decisions. We developed a prognostic model for estimation of long-term survival of critically ill patients. METHODOLOGY AND PRINCIPAL FINDINGS: This was a retrospective linked data cohort study involving 11,930 critically ill patients who survived more than 5 days in a university teaching hospital in Western Australia. Older age, male gender, co-morbidities, severe acute illness as measured by Acute Physiology and Chronic Health Evaluation II predicted mortality, and more days of vasopressor or inotropic support, mechanical ventilation, and hemofiltration within the first 5 days of intensive care unit admission were associated with a worse long-term survival up to 15 years after the onset of critical illness. Among these seven pre-selected predictors, age (explained 50% of the variability of the model, hazard ratio [HR] between 80 and 60 years old = 1.95) and co-morbidity (explained 27% of the variability, HR between Charlson co-morbidity index 5 and 0 = 2.15) were the most important determinants. A nomogram based on the pre-selected predictors is provided to allow estimation of the median survival time and also the 1-year, 3-year, 5-year, 10-year, and 15-year survival probabilities for a patient. The discrimination (adjusted c-index = 0.757, 95% confidence interval 0.745-0.769) and calibration of this prognostic model were acceptable. SIGNIFICANCE: Age, gender, co-morbidities, severity of acute illness, and the intensity and duration of intensive care therapy can be used to estimate long-term survival of critically ill patients. Age and co-morbidity are the most important determinants of long-term prognosis of critically ill patients

A genomic storm in critically injured humans

Critical injury in humans induces a genomic storm with simultaneous changes in expression of innate and adaptive immunity genes

Age-based disparities in end-of-life decisions in Belgium: a population-based death certificate survey

<p>Abstract</p> <p>Background</p> <p>A growing body of scientific research is suggesting that end-of-life care and decision making may differ between age groups and that elderly patients may be the most vulnerable to exclusion of due care at the end of life. This study investigates age-related disparities in the rate of end-of-life decisions with a possible or certain life shortening effect (ELDs) and in the preceding decision making process in Flanders, Belgium in 2007, where euthanasia was legalised in 2002. Comparing with data from an identical survey in 1998 we also study the plausibility of the ‘slippery slope’ hypothesis which predicts a rise in the rate of administration of life ending drugs without patient request, especially among elderly patients, in countries where euthanasia is legal.</p> <p>Method</p> <p>We performed a post-mortem survey among physicians certifying a large representative sample (n = 6927) of death certificates in 2007, identical to a 1998 survey. Response rate was 58.4%.</p> <p>Results</p> <p>While the rates of non-treatment decisions (NTD) and administration of life ending drugs without explicit request (LAWER) did not differ between age groups, the use of intensified alleviation of pain and symptoms (APS) and euthanasia/assisted suicide (EAS), as well as the proportion of euthanasia requests granted, was bivariately and negatively associated with patient age. Multivariate analysis showed no significant effects of age on ELD rates. Older patients were less often included in decision making for APS and more often deemed lacking in capacity than were younger patients. Comparison with 1998 showed a decrease in the rate of LAWER in all age groups except in the 80+ age group where the rate was stagnant.</p> <p>Conclusion</p> <p>Age is not a determining factor in the rate of end-of-life decisions, but is in decision making as patient inclusion rates decrease with old age. Our results suggest there is a need to focus advance care planning initiatives on elderly patients. The slippery slope hypothesis cannot be confirmed either in general or among older people, as since the euthanasia law fewer LAWER cases were found.</p

Risk factors for multi-drug resistant Acinetobacter baumannii bacteremia in patients with colonization in the intensive care unit

<p>Abstract</p> <p>Background</p> <p>Epidemic outbreaks of multi-drug resistant (MDR) <it>Acinetobacter baumannii </it>(AB) in intensive care units (ICUs) are increasing. The incidence of MDR AB bacteremia, which develops as a result of colonization, is increasing through widespread dissemination of the pathogen, and further colonization. We sought to determine risk factors for MDR AB bacteremia in patients colonized with MDR AB in the ICU.</p> <p>Methods</p> <p>We conducted a retrospective, observational study of 200 patients colonized with MDR AB in the ICU at Severance Hospital, South Korea during the outbreak period between January 2008 and December 2009.</p> <p>Results</p> <p>Of the 200 patients colonized with MDR AB, 108 developed MDR AB bacteremia, and 92 did not. APACHE II scores were higher in bacteremic than non-bacteremic patients at the time of ICU admission and colonization (24.0 vs. 21.6; <it>P </it>= 0.035, 22.9 vs. 16.8; <it>P </it>< 0.001, respectively). There was no difference between the two groups in the duration of time from ICU admission to colonization (7.1 vs. 7.2 days; <it>P </it>= 0.923), but the duration of time at risk was shorter in bacteremic patients (12.1 vs. 6.0 days; <it>P </it>= 0.016). A recent invasive procedure was a significant risk factor for development of bacteremia (odds ratio = 3.85; 95% CI 1.45-10.24; <it>P </it>= 0.007). Multivariate analysis indicated infection and respiratory failure at the time of ICU admission, maintenance of mechanical ventilation, maintenance of endotracheal tube instead of switching to a tracheostomy, recent central venous catheter insertion, bacteremia caused by other microorganism after colonization by MDR AB, and prior antimicrobial therapy, were significant risk factors for MDR AB bacteremia.</p> <p>Conclusions</p> <p>Patients in the ICU, colonized with MDR AB, should be considered for minimizing invasive procedures and early removal of the invasive devices to prevent development of MDR AB bacteremia.</p

Cyanobacterial lipopolysaccharides and human health – a review

Cyanobacterial lipopolysaccharide/s (LPS) are frequently cited in the cyanobacteria literature as toxins responsible for a variety of heath effects in humans, from skin rashes to gastrointestinal, respiratory and allergic reactions. The attribution of toxic properties to cyanobacterial LPS dates from the 1970s, when it was thought that lipid A, the toxic moiety of LPS, was structurally and functionally conserved across all Gram-negative bacteria. However, more recent research has shown that this is not the case, and lipid A structures are now known to be very different, expressing properties ranging from LPS agonists, through weak endotoxicity to LPS antagonists. Although cyanobacterial LPS is widely cited as a putative toxin, most of the small number of formal research reports describe cyanobacterial LPS as weakly toxic compared to LPS from the Enterobacteriaceae. We systematically reviewed the literature on cyanobacterial LPS, and also examined the much lager body of literature relating to heterotrophic bacterial LPS and the atypical lipid A structures of some photosynthetic bacteria. While the literature on the biological activity of heterotrophic bacterial LPS is overwhelmingly large and therefore difficult to review for the purposes of exclusion, we were unable to find a convincing body of evidence to suggest that heterotrophic bacterial LPS, in the absence of other virulence factors, is responsible for acute gastrointestinal, dermatological or allergic reactions via natural exposure routes in humans. There is a danger that initial speculation about cyanobacterial LPS may evolve into orthodoxy without basis in research findings. No cyanobacterial lipid A structures have been described and published to date, so a recommendation is made that cyanobacteriologists should not continue to attribute such a diverse range of clinical symptoms to cyanobacterial LPS without research confirmation