Daniel Lew

Lenercept (p55 tumor necrosis factor receptor fusion protein) in severe sepsis and early septic shock: a randomized, double-blind, placebo-controlled, multicenter phase III trial with 1,342 patients.

ObjectivePhase III study to confirm a trend observed in a previous phase II study showing that a single dose of lenercept, human recombinant p55 tumor necrosis factor receptor-immunoglobulin G1 (TNFR55-IgG1) fusion protein, decreased mortality in patients with severe sepsis or early septic shock. DesignMulticenter, double-blind, phase III, placebo-controlled, randomized study. SettingA total of 108 community and university-affiliated hospitals in the United States (60), Canada (6) and Europe (42). PatientsA total of 1,342 patients were recruited who fulfilled the entry criteria within the 12-hr period preceding the study drug administration. InterventionAfter randomization, an intravenous dose of 0.125 mg/kg lenercept or placebo was given. The patient was monitored for up to 28 days, during which standard diagnostic, supportive, and therapeutic care was provided. Measurements and Main Results The primary outcome measure was 28-day all-cause mortality. Baseline characteristics were as follows: a total of 1,342 patients were randomized; 662 received lenercept and 680 received placebo. The mean age was 60.5 yrs (range, 17–96 yrs); 39% were female; 65% had medical admissions, 8% had scheduled surgical admissions, and 27% had unscheduled surgical admissions; 73% had severe sepsis without shock, and 27% had severe sepsis with early septic shock. Lenercept and placebo groups were similar at baseline with respect to demographic characteristics, simplified acute physiology score II-predicted mortality, profiles of clinical site of infection and microbiological documentation, number of dysfunctioning organs, and interleukin-6 (IL-6) plasma concentration. Lenercept pharmacokinetics were similar in severe sepsis and early septic shock patients. Tumor necrosis factor was bound in a stable manner to lenercept as reflected by the accumulation of total serum tumor necrosis factor &agr; concentrations. There were 369 deaths, 177 on lenercept (27% mortality) and 192 on placebo (28% mortality). A one-sided Cochran-Armitage test, stratified by geographic region and baseline, predicted 28-day all-cause mortality (simplified acute physiology score II), gave a p value of .141 (one-sided). Lenercept treatment had no effect on incidence or resolution of organ dysfunctions. There was no evidence that lenercept was detrimental in the overall population. ConclusionLenercept had no significant effect on mortality in the study population.

Low incidence of haematogenous seeding to total hip and knee prostheses in patients with remote infections

OBJECTIVES The exposure of joint prostheses to remote infections is unknown. We wanted to estimate (a) the exposure of arthroplasty patients to severe remote infections, and (b) the incidence of arthroplasty infections associated with remote infections. METHODS Prospective cohort study of all elective hip and knee arthroplasties performed between March 1996 and September 2008, with retrospective documentation of remote infections in hospitalized patients. RESULTS A total of 6101 elective total joint arthroplasties, consisting of 4002 hip replacements (66%) and 2099 knee replacements (34%), were included. The mean follow-up was 70 months. During the study period, the cohort patients experienced 553 remote infections after a median delay of 33 months post-arthroplasty. There were 71 prosthetic infections detected, 7 (total incidence 7/6101, 0.1%) of which were secondary to a remote infection. The ratio of infections associated with remote infections to potential exposure was 1:79. Among hip arthroplasty patients the incidence rate was 1.4 infections associated with remote infections per 10,000 patient-years of follow-up. Infections associated with remote infections occurred later than surgical site infections, (46 months vs. 19 months post-surgery, respectively; mean difference 27 months, 95% CI 8-45 months). CONCLUSIONS Arthroplasty infections associated with remote infections were rare, and occurred like their potential exposure mostly more than 24 months post-arthroplasty.

Successful Treatment of Paecilomyces lilacinus Endophthalmitis with Voriconazole

Paecilomyces lilacinus is a rare cause of endophthalmitis and there are few reports of it in the literature. Herein we report a patient with P. lilacinus endophthalmitis who was treated with the new triazole, voriconazole, for 4 months, with a good clinical evolution. This treatment appears to be a valuable new therapeutic option but requires further clinical confirmation.

Activity and impact on antibiotic use and costs of a dedicated infectious diseases consultant on a septic orthopaedic unit.

UNLABELLED The Orthopaedic Service of the Geneva University Hospitals engages dedicated infectious disease (ID) specialists to assist in the treatment of infected patients. We investigated the daily clinical activity and the impact on antibiotic costs in the Septic Unit since 2000. METHODS Retrospective analysis of various databases. Prospective survey of clinical activity from January 2008 to March 2008. RESULTS According to the survey, the ID specialist performed 265 first-time and 1420 follow-up consultations (average of 11.4 consultations per working day). In 88% of cases the antibiotic regimen initiated by the surgeons was approved. When the ID specialist had to change antibiotic treatment, it was for de-escalation in 43.7%, discontinuance in 32.4%, and initiation in 24.4% of cases. From April 2007 to March 2008, the ID specialist decreased total antibiotic use by 43 DDD/100 patients-days (p=0.0006) in the Septic Unit. Direct antibiotic costs decreased by US

Meropenem (1.5 g/day) is as effective as imipenem/cilastatin (2 g/day) for the treatment of moderately severe intra-abdominal infections

64,380 over the same period, equal to the annual salary of the ID specialist. There was no change in the number of recurrent infections. CONCLUSIONS The main antibiotic-related activity of the dedicated orthopaedic ID specialist in Geneva our institution was to discontinue or adjust a pre-existing antimicrobial therapy. This activity significantly reduced antibiotic use and related costs on a septic orthopaedic unit.

Infectious olecranon and patellar bursitis: short-course adjuvant antibiotic therapy is not a risk factor for recurrence in adult hospitalized patients

This multicentre, open-label, randomised trial compared meropenem (0.5 g/8 h) and imipenem/cilastatin (at the commonly used dosage of 0.5 g/6 h) in monotherapy in patients with moderately severe intra-abdominal infections (IAIs). In total, 161 patients were randomised (82 meropenem, 79 imipenem/cilastatin). The mean APACHE II scores in the two groups were 5.8 and 6.4, respectively. At the end of therapy, 65/71 (91.6%) evaluable meropenem recipients were clinically cured or improved, compared to 60/64 (93.8%) imipenem/cilastatin recipients. This difference and that in an intention-to-treat analysis (82.1 vs 86.1%, respectively), were not statistically significant. Both drugs were generally well tolerated. Thus, meropenem 0.5 g/8 h is as clinically effective and well tolerated as imipenem/cilastatin 0.5 g/6 h in moderately severe IAIs.

The value of bacterial culture during clean orthopedic surgery: a prospective study of 1,036 patients.

OBJECTIVES No evidence-based recommendations exist for the management of infectious bursitis. We examined epidemiology and risk factors for recurrence of septic bursitis. Specifically, we compared outcome in patients receiving bursectomy plus short-course adjuvant antibiotic therapy (<or=7 days) with that of patients receiving bursectomy plus longer-course antibiotic therapy (>7 days). PATIENTS AND METHODS Retrospective study of adult patients with infectious olecranon and patellar bursitis requiring hospitalization at Geneva University Hospital from January 1996 to March 2009. RESULTS We identified 343 episodes of infectious bursitis (237 olecranon and 106 patellar). Staphylococcus aureus predominated among the 256 cases with an identifiable pathogen (85%). Three hundred and twelve cases (91%) were treated surgically; 142 (41%) with one-stage bursectomy and closure and 146 with two-stage bursectomy. All received antibiotics for a median duration of 13 days with a median intravenous component of 3 days. Cure was achieved in 293 (85%) episodes. Total duration of antibiotic therapy [odds ratio (OR) 0.9; 95% confidence interval (95% CI) 0.8-1.1] showed no association with cure. In multivariate analysis, only immunosuppression was linked to recurrence (OR 5.6; 95% CI 1.9-18.4). Compared with <or=7 days, 8-14 days of antibiotic treatment (OR 0.6; 95% CI 0.1-2.9) or >14 days of antibiotic treatment (OR 0.9; 95% CI 0.1-10.7) was equivalent, as was the intravenous component (OR 1.1; 95% CI 1.0-1.3). CONCLUSIONS In severe infectious bursitis requiring hospitalization, adjuvant antibiotic therapy might be limited to 7 days in non-immunosuppressed patients.

Should we continue using amphotericin B deoxycholate for the treatment of fungal infections? Adverse events and clinical outcomes.

OBJECTIVE To determine whether bacterial cultures of the wounds of patients undergoing clean orthopedic surgery would help predict infection. METHODS During 1 year, 1,256 cultures were performed for 1,102 patients who underwent clean orthopedic surgery. Results were analyzed to evaluate their ability to predict postoperative infection. RESULTS The sensitivity, specificity, positive predictive value, and negative predictive value of the cultures were 38%, 92%, 7%, and 99%, respectively. CONCLUSIONS Cultures performed during clean orthopedic surgery were not useful for predicting postoperative infection.

Tracking methicillin-resistant Staphylococcus aureus clones in Colombian hospitals over 7 years (1996-2003): emergence of a new dominant clone.

Amphotericin B deoxycholate (AmBd) has been a standard therapy for IFI but is associated with high adverse event and mortality rates. A retrospective review was undertaken to describe adverse events and clinical outcomes in adult patients with IFI treated with only AmBd as initial therapy.