Ertapenem versus piperacillin/tazobactam for the treatment of complicated infections: a meta-analysis of randomized controlled trials

<p>Abstract</p> <p>Background</p> <p>Ertapenem, a new carbapenem with a favorable pharmacokinetic profile, has been approved for the treatment of complicated intra-abdominal Infections (cIAIs), acute pelvic infections (APIs) and complicated skin and skin-structure infections (cSSSIs). The aim of this study is to compare the efficacy and safety of ertapenem with piperacillin/tazobactam, which has been reported to possess good efficacy for the treatment of these complicated infections.</p> <p>Methods</p> <p>We performed a meta-analysis of randomized controlled trials identified in PubMed, Cochrane library and Embase that compared the efficacy and safety of ertapenem with piperacillin/tazobactam for the treatment of complicated infections including cIAIs, APIs, cSSSIs. The primary efficacy outcome was clinical treatment success assessed at the test-of-cure visit. The primary safety outcome was drug related clinical and laboratory adverse events occurred during the treatment and the post-treatment period.</p> <p>Result</p> <p>Six RCTs, involving 3161 patients, were included in our meta-analysis. Ertapenem was associated similar clinical treatment success with piperacillin/tazobactam for complicated infections treatment (clinically evaluable population, 1937 patients, odds ratios: 1.15, 95% confidence intervals: 0.89-1.49; modified intention to treat population, 2855 patients, odds ratios: 1.03, 95% confidence intervals: 0.87-1.22). All of secondary efficacy outcomes analysis obtained similar findings with clinical treatment success. No difference was found about the incidence of drug related adverse events between ertapenem and piperacillin/tazobactam groups.</p> <p>Conclusion</p> <p>This meta-analysis provides evidence that ertapenem 1 g once a day can be used as effectively and safely as recommended dose of piperacillin/tazobactam, for the treatment of complicated infections, particularly of mild to moderate severity. It is an appealing option for the treatment of these complicated infections.</p

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

Comparative antimicrobial susceptibility of aerobic and facultative bacteria from community-acquired bacteremia to ertapenem in Taiwan

<p>Abstract</p> <p>Background</p> <p>Ertapenem is a once-a-day carbapenem and has excellent activity against many gram-positive and gram-negative aerobic, facultative, and anaerobic bacteria. The susceptibility of isolates of community-acquired bacteremia to ertapenem has not been reported yet. The present study assesses the in vitro activity of ertapenem against aerobic and facultative bacterial pathogens isolated from patients with community-acquired bacteremia by determining and comparing the MICs of cefepime, cefoxitin, ceftazidime, ceftriaxone, ertapenem, piperacillin, piperacillin-tazobactam, ciprofloxacin, amikacin and gentamicin. The prevalence of extended broad spectrum β-lactamases (ESBL) producing strains of community-acquired bacteremia and their susceptibility to these antibiotics are investigated.</p> <p>Methods</p> <p>Aerobic and facultative bacteria isolated from blood obtained from hospitalized patients with community-acquired bacteremia within 48 hours of admission between August 1, 2004 and September 30, 2004 in Chang Gung Memorial Hospital at Keelung, Taiwan, were identified using standard procedures. Antimicrobial susceptibility was evaluated by Etest according to the standard guidelines provided by the manufacturer and document M100-S16 Performance Standards of the Clinical Laboratory of Standard Institute. Antimicrobial agents including cefepime, cefoxitin, ceftazidime, ceftriaxone, ertapenem, piperacillin, piperacillin-tazobactam, ciprofloxacin, amikacin and gentamicin were used against the bacterial isolates to test their MICs as determined by Etest. For <it>Staphylococcus aureus </it>isolates, MICs of oxacillin were also tested by Etest to differentiate oxacillin-sensitive and oxacillin-resistant <it>S. aureus</it>.</p> <p>Results</p> <p>Ertapenem was highly active in vitro against many aerobic and facultative bacterial pathogens commonly recovered from patients with community-acquired bacteremia (128/159, 80.5 %). Ertapenem had more potent activity than ceftriaxone, piperacillin-tazobactam, or ciprofloxacin against oxacillin-susceptible <it>S</it>. <it>aureus </it>(17/17, 100%)and was more active than any of these agents against <it>enterobacteriaceae </it>(82/82, 100%).</p> <p>Conclusion</p> <p>Based on the microbiology pattern of community-acquired bacteremia, initial empiric treatment that requires coverage of a broad spectrum of both gram-negative and gram-positive aerobic bacteria, such as ertapenem, may be justified in moderately severe cases of community-acquired bacteremia in non-immunocompromised hosts.</p

Burn Injury Reduces Neutrophil Directional Migration Speed in Microfluidic Devices

Thermal injury triggers a fulminant inflammatory cascade that heralds shock, end-organ failure, and ultimately sepsis and death. Emerging evidence points to a critical role for the innate immune system, and several studies had documented concurrent impairment in neutrophil chemotaxis with these post-burn inflammatory changes. While a few studies suggest that a link between neutrophil motility and patient mortality might exist, so far, cumbersome assays have prohibited exploration of the prognostic and diagnostic significance of chemotaxis after burn injury. To address this need, we developed a microfluidic device that is simple to operate and allows for precise and robust measurements of chemotaxis speed and persistence characteristics at single-cell resolution. Using this assay, we established a reference set of migration speed values for neutrophils from healthy subjects. Comparisons with samples from burn patients revealed impaired directional migration speed starting as early as 24 hours after burn injury, reaching a minimum at 72–120 hours, correlated to the size of the burn injury and potentially serving as an early indicator for concurrent infections. Further characterization of neutrophil chemotaxis using this new assay may have important diagnostic implications not only for burn patients but also for patients afflicted by other diseases that compromise neutrophil functions

Efficacy and safety of tigecycline monotherapy vs. imipenem/cilastatin in Chinese patients with complicated intra-abdominal infections: a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Tigecycline, a first-in-class broad-spectrum glycylcycline antibiotic, has broad-spectrum in vitro activity against bacteria commonly encountered in complicated intra-abdominal infections (cIAIs), including aerobic and facultative Gram-positive and Gram-negative bacteria and anaerobic bacteria. In the current trial, tigecycline was evaluated for safety and efficacy vs. imipenem/cilastatin in hospitalized Chinese patients with cIAIs.</p> <p>Methods</p> <p>In this phase 3, multicenter, open-label study, patients were randomly assigned to receive IV tigecycline or imipenem/cilastatin for ≤2 weeks. The primary efficacy endpoints were clinical response at the test-of-cure visit (12-37 days after therapy) for the microbiologic modified intent-to-treat and microbiologically evaluable populations. Because the study was not powered to demonstrate non-inferiority between tigecycline and imipenem/cilastatin, no formal statistical analysis was performed. Two-sided 95% confidence intervals (CIs) were calculated for the response rates in each treatment group and for differences between treatment groups for descriptive purposes.</p> <p>Results</p> <p>One hundred ninety-nine patients received ≥1 dose of study drug and comprised the modified intent-to-treat population. In the microbiologically evaluable population, 86.5% (45 of 52) of tigecycline- and 97.9% (47 of 48) of imipenem/cilastatin-treated patients were cured at the test-of-cure assessment (12-37 days after therapy); in the microbiologic modified intent-to-treat population, cure rates were 81.7% (49 of 60) and 90.9% (50 of 55), respectively. The overall incidence of treatment-emergent adverse events was 80.4% for tigecycline vs. 53.9% after imipenem/cilastatin therapy (<it>P </it>< 0.001), primarily due to gastrointestinal-related events, especially nausea (21.6% vs. 3.9%; <it>P </it>< 0.001) and vomiting (12.4% vs. 2.0%; <it>P </it>= 0.005).</p> <p>Conclusions</p> <p>Clinical cure rates for tigecycline were consistent with those found in global cIAI studies. The overall safety profile was also consistent with that observed in global studies of tigecycline for treatment of cIAI, as well as that observed in analyses of Chinese patients in those studies; no novel trends were observed.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov NCT00136201</p