Ertapenem or ticarcillin/clavulanate for the treatment of intra-abdominal infections or acute pelvic infections in pediatric patients.

BACKGROUND: Ertapenem, a group I carbapenem antibiotic, has been shown to be safe and effective in treating adults with complicated intra-abdominal (cIAI) or acute pelvic infection (API). This study evaluated ertapenem for treating these infections in children. METHODS: In an open-label study, children aged 2 to 17 years with cIAI or API were randomized 3:1 to receive ertapenem or ticarcillin/clavulanate. Children 13 to 17 years of age received 1 g parenterally daily, and those 2 to 12 years of age received 15 mg/kg twice daily. Patients < 60 kg received ticarcillin/clavulanate 50 mg/kg 4 to 6 times daily and 3.1 g 4 to 6 times daily for those > or = 60 kg. Patients were assessed for safety and tolerability throughout the study and for efficacy after the completion of therapy. RESULTS: One hundred five patients, 72 (69%) with cIAI, received > or = 1 dose of study drug and were included in the safety analysis. Eighty-one patients were treated with ertapenem. Infusion site pain was the most common drug-related adverse event in both groups. In the modified intent-to-treat analysis, the age-adjusted posttreatment clinical response rates were 87% (43/50 patients) and 100% (25/25 patients) in the cIAI and API patients, respectively, for ertapenem and 73% (11/15 evaluable patients) and 100% (8/8 evaluable patients), respectively, for ticarcillin/clavulanate. Overall age-adjusted response rates were 91% (68/75 evaluable patients) for ertapenem and 83% (19/23 evaluable patients) for the comparator. CONCLUSIONS: This study suggests that ertapenem is generally safe and efficacious for treating cIAI or API in pediatric patients.

Current guidelines produce competent endovascular surgeons.

OBJECTIVE: This study was conducted to evaluate the safety of percutaneous endovascular procedures (PEPs) during integration of endovascular skills into an urban academic vascular surgery practice and assess the hypothesis that currently accepted guidelines are a valid benchmark for endovascular competency. METHODS: From 2000 through 2004, an endovascular training paradigm was instituted to integrate endovascular procedures into an academic endovascular practice. The paradigm involved individual mentoring of vascular surgery faculty by a partner with mature endovascular skills. Mentoring continued until each surgeon achieved a procedural experience of 100 diagnostic angiograms and 50 percutaneous endovascular interventions. Once achieved, privileges were granted for independent endovascular practice. To assess the effectiveness of the training process and competency of the newly trained endovascular practitioner, the surgeon-specific 30-day incidence of major complications and deaths for all PEPs performed during and after the mentoring process was determined. Complications and deaths were assigned to the mentor during the training process and to the individual surgeon once endovascular privileges were granted. Complications were classified as local vascular, local nonvascular, or systemic/remote. RESULTS: From 2000 through 2004, 1208 PEPs were performed. During this time, three faculty surgeons achieved sufficient endovascular procedural experience and were granted endovascular privileges. Major complications consisted of 17 local vascular, three local nonvascular, and four systemic/remote. Three deaths occurred. Renal percutaneous transluminal angioplasty/stent procedures had the highest complication and death rate at 9%. The major complication and death rate per year was 1.8% to 4.9% (P = .32) and did not significantly vary. The major complication and death rate for all 1208 PEPs was 2.2%. The surgeon-specific complication and death rate was 1.9% to 3.6% (P = .14) and did not vary between surgeons. CONCLUSION: Endovascular skills can be safely transferred using a vascular surgeon-based training paradigm. When the training paradigm is directed at satisfying currently recommended guidelines for endovascular privileging, competent endovascular surgeons are the result.

A multicenter trial of the efficacy and safety of tigecycline versus imipenem/cilastatin in patients with complicated intra-abdominal infections [Study ID Numbers: 3074A1-301-WW; ClinicalTrials.gov Identifier: NCT00081744].

BACKGROUND: Complicated intra-abdominal infections (cIAI) remain challenging to treat because of their polymicrobial etiology including multi-drug resistant bacteria. The efficacy and safety of tigecycline, an expanded broad-spectrum glycylcycline antibiotic, was compared with imipenem/cilastatin (IMI/CIS) in patients with cIAI. METHODS: A prospective, double-blind, multinational trial was conducted in which patients with cIAI randomly received intravenous (IV) tigecycline (100 mg initial dose, then 50 mg every 12 hours [q12h]) or IV IMI/CIS (500/500 mg q6h or adjusted for renal dysfunction) for 5 to14 days. Clinical response at the test-of-cure (TOC) visit (14-35 days after therapy) for microbiologically evaluable (ME) and microbiological modified intent-to-treat (m-mITT) populations were the co-primary efficacy endpoint populations. RESULTS: A total of 825 patients received >or= 1 dose of study drug. The primary diagnoses for the ME group were complicated appendicitis (59%), and intestinal (8.8%) and gastric/duodenal perforations (4.6%). For the ME group, clinical cure rates at TOC were 80.6% (199/247) for tigecycline versus 82.4% (210/255) for IMI/CIS (95% CI -8.4, 5.1 for non-inferiority tigecycline versus IMI/CIS). Corresponding clinical cure rates within the m-mITT population were 73.5% (227/309) for tigecycline versus 78.2% (244/312) for IMI/CIS (95% CI -11.0, 2.5). Nausea (31.0% tigecycline, 24.8% IMI/CIS [P = 0.052]), vomiting (25.7% tigecycline, 19.4% IMI/CIS [P = 0.037]), and diarrhea (21.3% tigecycline, 18.9% IMI/CIS [P = 0.435]) were the most frequently reported adverse events. CONCLUSION: This study demonstrates that tigecycline is as efficacious as imipenem/cilastatin in the treatment of patients with cIAI.

Influence of transmetatarsal amputation in patients requiring lower extremity distal revascularization.

When a transmetatarsal amputation (TMA) is required, successful long-term limb salvage is questioned. We evaluated the influence of TMA on limb salvage in patients undergoing lower extremity revascularization. Patients who had distal bypasses extending to the infrapopliteal arterial tree and adjunctive TMA were retrospectively reviewed. Limb salvage was determined with life-table analysis. Twenty-four patients (29 limbs) were evaluated: 15 male and 9 female. Average age was 64.2 years old. Gangrene was the indication for bypass and TMA in 25 (86.2%) patients. Seven limbs were lost to follow-up. Nine of the remaining 22 limbs required below-knee (8) or above-knee (1) amputations, seven limbs within the first 3 months. In the group of patients who had major amputations within the first 3 months, graft thrombosis was the cause of leg amputation in six (85.7%) cases. No significant predictors of early major amputation were identified. Limb salvage was 62 per cent at 1 year in the TMA group. In comparison, among historical controls requiring distal revascularization and no adjunctive toe or foot amputations, limb salvage was 76.5 per cent (P = NS). Long-term limb salvage is dependent on successful lower extremity revascularization. Requirement for TMA should not influence the decision for limb salvage.

Renal revascularization in Takayasu arteritis-induced renal artery stenosis.

PURPOSE: This study was undertaken to define the long-term effects of renal revascularization on blood pressure, and renal and cardiac function in patients with Takayasu arteritis-induced renal artery stenosis (TARAS). METHODS: Twenty-seven patients (25 women; mean age, 27 years) with TARAS underwent intervention. Primary, primary assisted, and secondary patency rates were determined, and the late effects on blood pressure, renal and cardiac function, and survival were analyzed. RESULTS: All patients had hypertension (mean blood pressure, 167/99 mm Hg; 2.5 antihypertensive medications per patient). Mean estimated glomerular filtration rate in patients not receiving hemodialysis was 76 mL/min, and in five patients serum creatinine concentration was greater than 1.5 mg/dL. Three patients were hemodialysis-dependent, and two had intractable congestive heart failure. Forty interventions were performed, including 32 aortorenal bypass procedures, two repeat implantations, four nephrectomies, and two transluminal angioplasty procedures. Postoperative morbidity was 19%. There were no deaths. During follow-up (mean, 68 months), three graft stenoses, all due to intimal hyperplasia, and three graft occlusions occurred. Two of three graft stenoses were successfully revised. At 1, 3, and 5 years of follow-up, primary patency was 87%, 79%, and 79%, respectively; primary assisted patency was 93%, 89%, 89%, respectively; and secondary patency was 93%, 89%, and 89%, respectively. Intervention resulted in a decrease in blood pressure to a mean of 132/79 mm Hg (P<.0001), and the need for antihypertensive medications was reduced to one per patient (P<.01). Mean glomerular filtration rate increased to 88 mL/min (P<.005), and two patients no longer required hemodialysis. Congestive heart failure resolved in both patients, and did not recur. There were three deaths during follow-up, with 5-year and 10-year actuarial survival of 96% and 80%, respectively. CONCLUSIONS: Renal revascularization to treat TARAS is durable, has a salutary effect on blood pressure, and enhances long-term renal and cardiac function. This response establishes renal revascularization as a successful and durable intervention for TARAS, and a benchmark to which other therapies should be compared.

Ertapenem versus piperacillin/tazobactam in the treatment of complicated intraabdominal infections: results of a double-blind, randomized comparative phase III trial.

OBJECTIVE: To examine the clinical efficacy and safety of ertapenem, a novel beta-lactam agent with wide activity against common pathogens encountered in intraabdominal infection. SUMMARY BACKGROUND DATA: Ertapenem has a pharmacokinetic profile and antimicrobial spectrum that support the potential for use as a once-a-day agent for the treatment of common mixed aerobic and anaerobic infections. METHODS This prospective, randomized, controlled, and double-blind trial was conducted to compare the safety and efficacy of ertapenem with piperacillin/tazobactam as therapy following adequate surgical management of complicated intraabdominal infections. RESULTS: Six hundred thirty-three patients were included in the modified intent-to-treat population, with 396 meeting all criteria for the evaluable population. Patients with a wide range of infections were enrolled; perforated or abscessed appendicitis was most common (approximately 60% in microbiologically evaluable population). A prospective, expert panel review was conducted to assess the adequacy of surgical source control in patients who were failures as a component of evaluability. For the modified intent-to-treat groups, 245 of 311 patients treated with ertapenem (79.3%) were cured, as were 232 of 304 (76.2) treated with piperacillin/tazobactam. One hundred seventy-six of 203 microbiologically evaluable patients treated with ertapenem (86.7%) were cured, as were 157 of the 193 (81.2%) treated with piperacillin/tazobactam. CONCLUSIONS: In this study, the efficacy of ertapenem 1 g once a day was equivalent to piperacillin/tazobactam 3.375 g every 6 hours in the treatment of a range of intraabdominal infections. Ertapenem was generally well tolerated and had a similar safety and tolerability profile to piperacillin/tazobactam. A formal process for review of adequacy of source control was found to be of benefit. The results of this trial suggest that ertapenem may be a useful option that could eliminate the need for combination and/or multidosed antibiotic regimens for the empiric treatment of intraabdominal infections.

Ertapenem monotherapy versus combination therapy with ceftriaxone plus metronidazole for treatment of complicated intra-abdominal infections in adults.

The efficacy and safety of intravenous (IV) ertapenem, 1 and 1.5 g once a day, for treatment of adults with complicated intra-abdominal infection were compared with those of IV ceftriaxone 2 g once a day plus IV metronidazole 500 mg every 8 h. After at least 3 days of IV therapy and satisfactory clinical response, patients could be switched to oral ciprofloxacin plus metronidazole. Fifty-nine patients were randomized to receive ertapenem 1 g and 51 to receive ertapenem 1.5 g; 55 patients were randomized to each comparator group. At the test of cure, 4-6 weeks post therapy, in the 1 g cohort, 84% (26/31) of patients treated with ertapenem and 85% (35/41) with comparator therapy had a favourable clinical and microbiological assessment. Success rates in the 1.5 g cohort were 83% (22/29) and 77% (24/31) in the ertapenem and comparator groups, respectively. Drug-related adverse events were generally similar in both treatment groups. Ertapenem 1 or 1.5 g once a day followed by optional oral therapy appeared similar to combined therapy with ceftriaxone plus metronidazole with the same optional oral switch for treatment of complicated intra-abdominal infections in adults. Although not compared directly in a randomized fashion, the efficacy and safety profiles of ertapenem 1 and 1.5 g appeared comparable. Ertapenem was generally well tolerated and had an overall safety profile similar to ceftriaxone plus metronidazole.