Ertapenem Group Research Articles

A randomized controlled trial of sitafloxacin vs. ertapenem as a switchtherapy after treatment for acute pyelonephritis caused by extended-spectrum β-lactamase-producing Escherichia coli: A pilot study.

The overuse and misuse of carbapenems have contributed to the antibiotic resistance crisis. The role of oral fluoroquinolones as a switch therapy for the treatment of urinary tract infection from Escherichia coli (ESBL-EC) is limited. To compare the clinical and bacteriological efficacy of sitafloxacin and ertapenem for non-bacteremic acute pyelonephritis caused by ESBL-EC. A prospective randomized controlled trial of patients with acute pyelonephritis caused by ESBL-EC was performed as a pilot study. One of the carbapenems was initially given to the patients. After day 3, patients were randomized to receive either sitafloxacin or ertapenem. Thirty-six patients were enrolled: 19 (52.8%) in the sitafloxacin group and 17 (47.2%) in the ertapenem group. There was no statistically significant difference in baseline characteristics between the two groups except a lower proportion of previous urinary catheter insertion in the sitafloxacin group (15.8% vs. 52.9%, p=0.018). Signs and symptoms at presentation were similar between the two groups except a higher proportion of patients with chills in the sitafloxacin group (68.4% vs. 29.4%, p=0.019). At day 10, all but one patient in the ertapenem group had clinical cure. Microbiological eradication was comparable between the sitafloxacin and ertapenem groups (84.2% vs. 75%, p=0.677). There were no significant adverse effects. Treatment of non-bacteremic acute pyelonephritis caused by ESBL-EC with carbapenem followed by oral sitafloxacin is effective and well-tolerated. Sitafloxacin may be considered as an alternative choice of switch therapy in this clinical setting.

Evaluating the Impact of Long-Term Outpatient Ertapenem (ETP) vs. Ceftriaxone (CTX) on Clinical Success and Development of Resistance for Documented Enterobacteriaceae Infections

BackgroundCeftriaxone and ertapenem are two commonly prescribed outpatient once-daily parenteral antimicrobials with activity against Enterobacteriaceae. However, there is minimal data evaluating the impact of long-term CTX and ETP therapy on development of resistance. Therefore, the goals of this study were to compare the development of resistance, incidence of Clostridium difficile colitis and clinical outcomes.MethodsWe conducted a single center, retrospective, case cohort study of all adult patients who completed at least 2 weeks of outpatient therapy. A list of adult patients receiving home ETP or CTX between 2011 and 2014 were screened for inclusion. The primary outcome was development of resistance during therapy or within 6 months of completing therapy, and secondary outcomes were mortality, readmission, clinical failure, C. difficileinfection and antibiotic cost.Results1,989 patients were screened and 188 were included: 115 patients in the ETP group and 73 in the CTX group. The most common reason for exclusion was lack of documented Enterobacteriaceae infection. Resistance developed in 13 (6.9%) of all patients, but there was no difference in the development of resistance between groups (ETP 7/115 (6.1%) vs. 6/73 (8.2%), P = 0.57). Similar rates of C. difficile colitis occurred between groups: 7 (6.1%) patients receiving ETP and 4 patients receiving CTX. There was no difference in mortality, clinical failure or readmission.The total cost per treatment course per patient was significantly more expensive in the ETP group ($3,604 vs $221, P = <0.001).ConclusionETP and CTX demonstrated similar rates of mortality, clinical failure, readmission, and the development of resistance or C. difficile colitis. However, ETP therapy was significantly more expensive, and could be a target for stewardship intervention in select patients receiving home antibiotic therapy.Disclosures All authors: No reported disclosures.

Assessing the Efficacy and Safety of Eravacycline vs Ertapenem in Complicated Intra-abdominal Infections in the Investigating Gram-Negative Infections Treated With Eravacycline (IGNITE 1) Trial

Eravacycline is a novel, fully synthetic fluorocycline antibiotic of the tetracycline class with in vitro activity against clinically important gram-negative, gram-positive aerobic, and facultative bacteria including most of those resistant to cephalosporins, fluoroquinolones, β-lactam/β-lactamase inhibitors, multidrug resistant strains and carbapenem-resistant Enterobacteriaceae, and most anaerobic pathogens. To evaluate the efficacy and safety of eravacycline compared with ertapenem in adult hospitalized patients with complicated intra-abdominal infections (cIAIs). This was a phase III, randomized, double-blind, multicenter study that evaluated the efficacy and safety of eravacycline in comparison with ertapenem in patients with cIAI requiring surgical or percutaneous intervention. The test-of-cure evaluation was conducted 25 to 31 days after the first dose of the study drug and the follow-up visit was conducted 38 to 50 days after the first dose of the study drug. All patients recruited into this study were hospitalized. Five hundred forty-one patients were recruited for this study; 270 patients were randomized to receive eravacycline, and 271 patients were randomized to receive ertapenem. Patients had to meet all of the following criteria: hospitalized for cIAI requiring intervention; 18 years or older; evidence of systemic inflammatory response; pain caused by cIAI; able to provide informed consent; and diagnosis of cIAI with sonogram or radiographic imaging or visual confirmation. Analyses were done in intent-to-treat and evaluable populations. Patients received eravacycline, 1.0 mg/kg every 12 hours, or ertapenem, 1.0 g every 24 hours, for a minimum of four 24-hour dosing cycles. Clinical outcome assessments were made at the end of treatment, test of cure, and follow-up visits and were classified as clinical cure, clinical failure, or indeterminate/missing. In total, 541 patients were randomly assigned to treatment: 270 in the eravacycline group and 271 in the ertapenem group. The mean ages were 54.9 years and 55.4 years for the eravacycline and ertapenem groups, respectively. Most patients were white (263 of 270 patients [97.4%] in the eravacycline group and 260 of 271 patients [95.9%] in the ertapenem group). For the microbiological intent-to-treat population, the rates of clinical cure at the test-of-cure visit were 86.8% in the eravacycline group and 87.6% in the ertapenem group. The difference in clinical cure rates between the groups was -0.80% (95% CI, -7.1% to 5.5%), meeting the prespecified noninferiority margin and allowing for statistical noninferiority of eravacycline to ertapenem to be declared for this study. Both study drugs were well tolerated. Overall, eravacycline demonstrated noninferiority to ertapenem for the treatment of patients with cIAI. Clinicaltrials.gov Identifier: NCT01844856.

The Effect of Different Carbapenem Antibiotics (Ertapenem, Imipenem/Cilastatin, and Meropenem) on Serum Valproic Acid Concentrations.

Carbapenem antibiotics (CBPMs) may significantly reduce the serum concentration of valproic acid (VPA), but the extent of this effect among various CBPMs is unknown. This study compared the extent and onset of the interactions among ertapenem, imipenem/cilastatin, and meropenem. A 5-year retrospective study was performed. Hospitalized patients over 18 years old who received VPA and a CBPM concurrently were enrolled via the pharmacy computer system. Patients who lacked VPA serum concentration measurements before or during CBPMs' use, had concurrent medication(s) that might interfere with VPA metabolism, or had a history of liver cirrhosis were excluded. Total VPA serum concentrations before and during CBPMs' use and after its discontinuation were recorded, and differences among various CBPMs were analyzed. Fifty-two patients were included in this analysis. Irrespective of the route of administration, VPA serum concentrations were subtherapeutic in 90% of the subjects during CBPMs' use. There was a significant decrease (P < 0.001) in VPA serum concentrations during the use of CBPMs: 72% ± 17%, 42% ± 22%, and 67% ± 19% in the ertapenem (N = 9), imipenem/cilastatin (N = 17), and meropenem (N = 26) groups, respectively. The effect of ertapenem and meropenem on VPA was significantly more expressed than that of imipenem/cilastatin (P < 0.005). The onset of this drug interaction occurred within 24 hours of CBPMs' administration, and VPA serum concentrations returned to 90% of baseline within 7 days of CBPMs' discontinuation along with a 20% increase in VPA dose. Increasing VPA dose during the use of ertapenem or meropenem did not result in elevating VPA serum concentrations to therapeutic levels during the combined therapy period. CBPMs reduced VPA serum concentration within 24 hours of administration by approximately 60%. Ertapenem and meropenem had a greater effect on VPA serum concentration than imipenem/cilastatin. Because of the dramatic reduction of VPA serum concentration during CBPMs' use, concomitant use of VPA and CBPMs should be avoided.

Treatment efficacy and superinfection rates in complicated urinarytract infections treated with ertapenem or piperacillin tazobactam.

In this retrospective study, the efficacy of ertapenem and piperacillin tazobactam was compared in the treatment of complicated urinary tract infections (cUTIs). Treatment responses were also evaluated for both antibiotics. A total of 230 patients were enrolled in the study. Of these, 170 received ertapenem and 60 received piperacillin-tazobactam. In both groups, urine cultures after 48 h were negative for the initial uropathogen. The frequency of superinfection was 29.4% in the ertapenem group and 8.3% in the piperacillin-tazobactam group over the duration of treatment (P < 0.05). Urinary catheterization increased the superinfection risk 2.88-fold in the ertapenem group and diabetes mellitus increased the risk 8.50-fold in the piperacillin-tazobactam group (CI: 1.44-5.76 and 1.16-62.09, respectively, P < 0.05). The main pathogen isolated from superinfection in the ertapenem group after 48 h was Enterococcus spp. (71.4%). Both ertapenem and piperacillin-tazobactam were effective in the treatment of cUTIs caused by ESBL-producing microorganisms. A high frequency of superinfection in the ertapenem group was the result of Enterococcus and Pseudomonas spp., against which ertapenem is not active. In the presence of urinary catheterization, diabetes mellitus, and urological intervention, patients should be closely monitored for the development of a superinfection, especially patients receiving ertapenem.

Ertapenem prophylaxis of surgical site infections in elective colorectal surgery in China: a multicentre, randomized, double-blind, active-controlled study.

Our purpose was to evaluate ertapenem versus ceftriaxone/metronidazole for prophylaxis of surgical site infections (SSIs) following elective colorectal surgery in Chinese adult patients. Eligible Chinese adults aged 18-80 years scheduled to undergo elective colorectal surgery by laparotomy were randomized to receive a 30 min infusion of 1 g of ertapenem/metronidazole placebo or 2 g of ceftriaxone/500 mg of metronidazole within 2 h before initial incision. The study endpoint was the proportion of patients with successful prophylaxis at 4 weeks after treatment. The primary analysis was based on the evaluable population (PP population) and the pre-specified non-inferiority margin was set at -15%. ClinicalTrials.gov: NCT01254344. Of 599 patients randomized, 499 (251 ertapenem and 248 ceftriaxone) were eligible for inclusion in the PP population. The proportions of patients with successful prophylaxis in the ertapenem and ceftriaxone groups were 90.4% (227/251) and 90.3% (224/248), respectively. The difference in the proportion of successful outcomes was 0.1% (95% CI -5.2%, 5.5%). Unexplained antibiotic use was the most frequent reason for prophylaxis failure in both groups [ertapenem 4.8% (12/251), ceftriaxone 4.4% (11/248); difference 0.3%; 95% CI -3.6, 4.3]. Pathogen species isolated from SSI sources were consistent with previously conducted studies and the product package insert. The incidence of adverse events (AEs) was similar between the groups, with the most common AE being pyrexia [ertapenem 7.6% (22/290), ceftriaxone 5.7% (17/297)]. Ertapenem is as effective as ceftriaxone/metronidazole for SSI prophylaxis in patients undergoing elective colorectal surgery, and is well tolerated.

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

Background Ertapenem has been demonstrated to be highly effective for the treatment of complicated infections. The aim of this study was to compare the efficacy and safety of ertapenem with ceftriaxone. Methods We searched the PubMed, EMBASE, and the Cochrane Library for published randomized controlled trials (RCTs) that compared the efficacy and safety of ertapenem with ceftriaxone for the treatment of complicated infections including community-acquired pneumonia (CAP), complicated urinary tract infections (cUTIs), and complicated intraabdominal infections (cIAIs). Meta-analysis was performed by RevMan 5.0. Results Eight RCTs, involving 2 883 patients, were included in our meta-analysis. Ertapenem was associated with similar clinical treatment success with ceftriaxone for complicated infections (1 326 patients, fixed-effect model, OR: 1.13, 95% CI: 0.75–1.71). There was no difference between the compared treatment groups with regard to the microbiological treatment success, and no difference was found with regard to the incidence of clinical and laboratory drug-related adverse events between ertapenem and ceftriaxone groups. As to local tolerability, overall, there was no difference between the compared groups; however, in the subgroup analysis, local reaction was significantly less in the ertapenem subgroup than the ceftriaxone plus ceftriaxone subgroup. Conclusions Ertapenem can be used as effectively and safely as ceftriaxone for the treatment of complicated infections. It is an appealing option for the treatment of these complicated infections.

Phase 2, Randomized, Double-Blind Study of the Efficacy and Safety of Two Dose Regimens of Eravacycline versus Ertapenem for Adult Community-Acquired Complicated Intra-Abdominal Infections

Eravacycline is a novel fluorocycline, highly active against Gram-positive and Gram-negative pathogens in vitro, including those with tetracycline and multidrug resistance. This phase 2, randomized, double-blind study was conducted to evaluate the efficacy and safety of two dose regimens of eravacycline compared with ertapenem in adult hospitalized patients with complicated intra-abdominal infections (cIAIs). Patients with confirmed cIAI requiring surgical or percutaneous intervention and antibacterial therapy were randomized (2:2:1) to receive eravacycline at 1.5 mg/kg of body weight every 24 h (q24h), eravacycline at 1.0 mg/kg every 12 h (q12h), or ertapenem at 1 g (q24h) for a minimum of 4 days and a maximum of 14 days. The primary efficacy endpoint was the clinical response in microbiologically evaluable (ME) patients at the test-of-cure (TOC) visit 10 to 14 days after the last dose of study drug therapy. Overall, 53 patients received eravacycline at 1.5 mg/kg q24h, 56 received eravacycline at 1.0 mg/kg q12h, and 30 received ertapenem. For the ME population, the clinical success rate at the TOC visit was 92.9% (39/42) in the group receiving eravacycline at 1.5 mg/kg q24h, 100% (41/41) in the group receiving eravacycline at 1.0 mg/kg q12h, and 92.3% (24/26) in the ertapenem group. The incidences of treatment-emergent adverse events were 35.8%, 28.6%, and 26.7%, respectively. Incidence rates of nausea and vomiting were low in both eravacycline groups. Both dose regimens of eravacycline were as efficacious as the comparator, ertapenem, in patients with cIAI and were well tolerated. These results support the continued development of eravacycline for the treatment of serious infections, including those caused by drug-resistant Gram-negative pathogens. (This study has been registered at ClinicalTrials.gov under registration no. NCT01265784.).

Perioperative Antimicrobial Prophylaxis for Intra-abdominal Surgery in Patients with Cancer: A Retrospective Study Comparing Ertapenem and Nonertapenem Antibiotics

To evaluate the role of ertapenem versus other standard antibiotic prophylaxis in patients with cancer undergoing intra-abdominal surgery. Our study was a retrospective cohort study consisting 615 patients who underwent intra-abdominal surgery at our institution between January 2007 and December 2010. The groups were divided among patients who received ertapenem as perioperative prophylaxis (ertapenem group) and patients who received other antibiotics (nonertapenem group). Groups were similar with respect to age, gender, and type of surgery. A total of 315 patients underwent colorectal and 300 noncolorectal surgeries. In a multivariate logistic regression model, the main factors associated with risk of surgical site infections (SSI) were as follows: antibiotics within 3 months of surgery (odds ratio [OR] 1.2, 95% confidence interval [CI] 1.04-1.54; p = 0.05), prior hospitalization within 1 year (OR 1.21, 95% CI 1.02-1.43; p = 0.05), diabetes mellitus (OR 2.1, 95% CI 1.7-3.4; p = 0.04), and perioperative prophylaxis other than ertapenem (OR 1.7, 95% CI 1.2-2.3; p = 0.04). Notably, patients who underwent colorectal surgery and received ertapenem had a lower rate of SSI (4% ertapenem vs. 13% nonertapenem, p = 0.01), whereas the frequency of infections was not different in patients who underwent other intra-abdominal surgery whether they received ertapenem or not. The use of ertapenem for perioperative prophylaxis in patients with colorectal surgery was associated with lower rates of SSI, while there was no difference in rates of infection in other intra-abdominal surgery.

Ertapenem versus Standard Triple Antibiotic Therapy for the Treatment of Perforated Appendicitis in Pediatric Patients: A Prospective Randomized Trial

The primary objective of this study was to compare triple therapy with ertapenem treatments in pediatric patients with perforated appendicitis, especially in terms of postoperative infectious complications. The secondary objective of this study was to assess the relative impact of therapy with ertapenem and triple antibiotic regimen on the emergence of resistant bacteria in bowel flora in the patients. Children aged 3 months to 17 years with perforated appendicitis were randomized 1:1 to receive ertapenem or triple therapy. Serial rectal cultures were obtained from participants enrolled in the study, allowing assessment of the relative impact of therapy with ertapenem and triple therapy on bowel colonization by resistant bacteria. In this study, 107 patients were included. No difference existed in time to full oral intake and regular diet, the length of antibiotic therapy, the length of the postoperative hospitalization, or the length of hospital stay between the two groups. Patients in the triple-therapy group were more likely to suffer from a postoperative infectious complication than those in the ertapenem group (6/54 vs. 2/53, p > 0.05). Bowel colonization with resistant organisms at the end of therapy in the triple-therapy group was significantly different than in the ertapenem group (35.2 vs. 11.3%, p < 0.05). Bowel colonization with resistant bacteria was less likely to occur after ertapenem treatment than triple therapy. 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 perforated appendicitis in children.

T.E.A. Study: three-day ertapenem versus three-day Ampicillin-Sulbactam

BackgroundIntra-abdominal infections are one of the most common infections encountered by a general surgeon. However, despite this prevalence, standardized guidelines outlining the proper use of antibiotic therapy are poorly defined due to a lack of clinical trials investigating the ideal duration of antibiotic treatment. The aim of this study is to compare the efficacy and safety of a three-day treatment regimen of Ampicillin-Sulbactam to that of a three-day regimen of Ertapenem in patients with localized peritonitis ranging from mild to moderate severity.MethodsThis study is a prospective, multi-center, randomized investigation performed in the Department of General, Emergency, and Transplant Surgery of St. Orsola-Malpighi University Hospital in Bologna, Italy. Discrete data were analyzed using the Chi-squared and Fisher exact tests. Differences between the two study groups were considered statistically significant for p-values less than 0.05.Results71 patients were treated with Ertapenem and 71 patients were treated with Ampicillin-Sulbactam. The two groups were comparable in terms of age and gender as well as the site of abdominal infection. Post-operative infection was identified in 12 patients: 10 with wound infections and 2 with intra-abdominal infections. In the Ertapenem group, 69 of the 71 patients (97%) were treated successfully, while the therapy failed in 2 cases (3%). Therapy failures were more frequent in the Unasyn group, amounting to 10 of 71 cases (p = 0.03).ConclusionAccording to these preliminary findings, the authors conclude that a three-day Ertapenem treatment regimen is the most effective antibiotic therapy for patients with localized intra-abdominal infections ranging from mild to moderate severity.Trial registrationTrial registration: ClinicalTrials.gov: NCT00630513

Comparison of Ertapenem and Ceftriaxone Therapy for Acute Pyelonephritis and Other Complicated Urinary Tract Infections in Korean Adults: A Randomized, Double-Blind, Multicenter Trial

The efficacy and safety of ertapenem, 1 g once daily, were compared with that of ceftriaxone, 2 g once daily, for the treatment of adults with acute pyelonephritis (APN) and complicated urinary tract infections (cUTIs) in a prospective, multicenter, double-blinded, randomized study. After ≥ 3 days of parenteral study therapy, patients could be switched to an oral agent. Of 271 patients who were initially stratified by APN (n = 210) or other cUTIs (n = 61), 66 (48.9%) in the ertapenem group and 71 (52.2%) in the ceftriaxone group were microbiologically evaluable. The mean duration of parenteral and total therapy, respectively, was 5.6 and 13.8 days for ertapenem and 5.8 and 13.8 days for ceftriaxone. The most common pathogen was Escherichia coli. At the primary efficacy endpoint 5-9 days after treatment, 58 (87.9%) patients in the ertapenem group and 63 (88.7%) in the ceftriaxone had a favorable microbiological response. When compared by stratum and severity, the outcomes in the two groups were equivalent. The frequency and severity of drug-related adverse events were generally similar in both treatment groups. The results indicate that ertapenem is highly effective and safe for the treatment of APN and cUTIs.

Ertapenem compared to combination drug therapy for the treatment of postpartum endometritis after cesarean delivery

Objective: Ertapenem is a broad spectrum carbapenem approved for the treatment of postpartum endometritis. Data regarding clinical outcomes after treatment with ertapenem for endometritis after cesarean delivery are limited. Our objectives were to compare clinical outcomes and cost of ertapenem versus a multi-drug regimen for treatment of endometritis after cesarean delivery. Methods: Retrospectively, patients with endometritis after cesarean delivery who were treated with ertapenem (group A) were compared to those treated with a combination regimen (group B). Mann–Whitney U and Fisher’s Exact were used for statistical analysis with p value <0.05 considered statistically significant. Results: Sixty-three patients were included: 31 in group A and 32 in group B. Demographics and intrapartum characteristics did not differ. Number of administered doses (A: 3, B: 11.5 p < 0.0001), cost (A: $156.63, B: $54.48 p < 0.0001) and nursing time in minutes (A: 6.6, B: 25.3 p < 0.0001) were different between both groups. Wound complications were higher in group A, occurring in 7 patients compared to 1 patient in group B (p = 0.024). Conclusion: Although time and number of administered doses were less in group A, given the high wound complication rate in patients treated with ertapenem, this drug may not be appropriate for all patients with endometritis after CD.

Clinical response to ertapenem in severe community-acquired pneumonia: a retrospective series in an elderly population

To evaluate in routine hospital practice the clinical response to ertapenem in comparison with other parenteral antibiotics in the treatment of community-acquired pneumonia (CAP), clinical records from patients with severe CAP treated with ertapenem from July 2002 to June 2006 in seven Spanish hospitals were retrospectively reviewed. Patients were classified according to the Pneumonia Severity Index (PSI). Each ertapenem-treated patient was matched with two patients in the same hospital treated with other antibiotics, according to age (difference ≤5 years), same PSI class and whether or not resident in a nursing home. Seventy-one patients treated with ertapenem and 131 matched controls were identified; 71 of the 202 patients came from nursing homes. A larger (p 0.0002) number of patients were treated with monotherapy in the ertapenem group. In total, 174 patients (86.1%) belonged to PSI classes IV–V; a higher (p <0.0001) PSI score was found in patients from nursing homes. The mean age was 80.5 years (75% of patients >76 years). Comorbidities were present in 193 patients (95.5%). No differences were found in median hospital stay (7 days for ertapenem vs. 10 days for comparators, p 0.066). A slightly higher clinical response rate was obtained for ertapenem vs. comparators (88.7% vs. 77.1%; p 0.0465; OR 2.25; 95% CI 0.99–5.12), with significant differences in clinical response in patients coming from nursing homes (95.8% ertapenem vs. 63.8% comparators; p 0.0034) but not in non-institutionalized patients (85.4% ertapenem vs. 84.5% comparators; p 0.929). The higher clinical response to ertapenem vs. comparators in severe CAP was due to its significantly higher efficacy in healthcare-associated CAP in patients coming from nursing homes.

Comparative Costs of Ertapenem and Cefotetan as Prophylaxis for Elective Colorectal Surgery

The costs of treating surgical site infections can be considerable. There is a cost associated with the prophylactic use of antibiotics; however, the use of prophylactic agents may reduce infection rates and lengths of stay, thus offsetting the overall treatment cost and potentially generating cost savings to hospitals. This project was intended to determine the potential cost impact of using ertapenem 1 g vs. cefotetan 2 g as prophylaxis for elective colorectal surgery. Cost analysis using efficacy data from the PREVENT clinical trial and drug acquisition and total hospital costs in 2005 dollars from Premier's Perspective Comparative Database in patients > or = 18 year of age, evaluable at four weeks after elective surgery of the colon or rectum and prophylactic treatment with ertapenem (n = 338) or cefotetan (n = 334). The primary outcome measures were the rate of prophylactic drug failure and the difference between the ertapenem and cefotetan groups in costs related to and total hospital stay. Prophylactic failure was defined as a surgical site infection, unexplained antibiotic use, or anastomotic leak. Prophylactic failure occurred in 28.1% of the patients receiving ertapenem and 42.8% of those receiving cefotetan (p < 0.05). The most common prophylactic failure was surgical site infection: 18.3% for ertapenem, 31.1% for cefotetan, difference (95% confidence interval) -13.0% (-19.5, -6.5%) (p < 0.05). The mean +/- standard deviation length of stay for all patients, including prophylactic successes and failures, was 7.6 +/- 6.6 days for ertapenem and 8.7 +/- 9.5 days for cefotetan. The mean per-patient cost of prophylactic drugs and hospital room and board was $15,245 with ertapenem and $17,428 cefotetan, a net difference of -$2,181. Ertapenem used in prophylaxis for elective colorectal operations results in a lower rate of surgical site infection and a shorter average length of stay than cefotetan. The calculated net difference in prophylactic antibiotic drug and hospital costs represents a saving of $2,181 per patient with ertapenem relative to cefotetan.

Profilaxia antimicrobiana na cirurgia bariátrica

OBJETIVO: Analisar os resultados da incidência de infecção do sítio cirúrgico com três diferentes esquemas antimicrobianos. MÉTODO: No período de Janeiro de 1999 a Dezembro de 2004 foram realizadas 716 cirurgias para o tratamento da Obesidade mórbida, seguindo a técnica proposta por Fobi/Capella. Foram estudados comparativamente três grupos de pacientes: Grupo I - (185) em que foi realizada a profilaxia antimicrobiana com ampicilina/sulbactam, na dose de 3g em duas doses; Grupo II (280) em que a profilaxia foi com ceftriaxona na dose de 1g (dose única); e Grupo III (251) em que a profilaxia foi com ertapenem, na dose de 1 g (dose única). RESULTADOS: O resultado do presente estudo demonstra taxas de infecção do sítio cirúrgico de 3,78% no grupo de profilaxia com ampicilina-sulbactam, 6,81% no grupo de profilaxia com ceftriaxona e de 1,99% no grupo de ertapenem. Não houve diferença estatisticamente significativa entre o uso da associação ampicilina/sulbactam ou ceftriaxona com relação à incidência de infecção do sítio cirúrgico. No entanto, quando comparados os resultados do Grupo II (Ceftriaxona) com o Grupo III (Ertapenem), houve uma diferença estatisticamente sisgnificante. CONCLUSÃO: A utilização do ertapenem, de maneira profilática, no tratamento cirúrgico da obesidade mórbida, determinou taxas de infecção do sítio cirúrgico estatisticamente inferiores ao grupo de ceftriaxona e similar ao de ampicilina-sulbactam.

Ertapenem versus Cefotetan Prophylaxis in Elective Colorectal Surgery

Ertapenem, a long-acting carbapenem, may be an alternative to the recommended prophylactic antibiotic cefotetan. In this randomized, double-blind trial, we assessed the efficacy and safety of antibiotic prophylaxis with ertapenem, as compared with cefotetan, in patients undergoing elective colorectal surgery. A successful outcome was defined as the absence of surgical-site infection, anastomotic leakage, or antibiotic use 4 weeks postoperatively. All adverse events were collected until 14 days after the administration of antibiotic prophylaxis. Of the 1002 patients randomly assigned to study groups, 901 (451 in the ertapenem group and 450 in the cefotetan group) qualified for the modified intention-to-treat analysis, and 672 (338 in the ertapenem group and 334 in the cefotetan group) were included in the per-protocol analysis. After adjustment for strata, in the modified intention-to-treat analysis, the rate of overall prophylactic failure was 40.2% in the ertapenem group and 50.9% in the cefotetan group (absolute difference, -10.7%; 95% confidence interval [CI], -17.1 to -4.2); in the per-protocol analysis, the failure rate was 28.0% in the ertapenem group and 42.8% in the cefotetan group (absolute difference, -14.8%; 95% CI, -21.9 to -7.5). Both analyses fulfilled statistical criteria for the superiority of ertapenem. In the modified intention-to-treat analysis, the most common reason for failure of prophylaxis in both groups was surgical-site infection: 17.1% in the ertapenem group and 26.2% in the cefotetan group (absolute difference, -9.1; 95% CI, -14.4 to -3.7). In the treated population, the overall incidence of Clostridium difficile infection was 1.7% in the ertapenem group and 0.6% in the cefotetan group (P=0.22). Ertapenem is more effective than cefotetan in the prevention of surgical-site infection in patients undergoing elective colorectal surgery but may be associated with an increase in C. difficile infection. (ClinicalTrials.gov number, NCT00090272 [ClinicalTrials.gov].).

Safety and tolerability of ertapenem.

Ertapenem is a Group 1 carbapenem that was licensed in the USA in November 2001 and in Europe in April 2002. Its safety profile has been assessed in 240 healthy volunteers participating in 12 clinical pharmacology studies and in 2046 patients enrolled in five Phase IIa and eight Phase IIb/III clinical trials. The most common drug-related adverse events (AEs) reported in trials comparing ertapenem and piperacillin-tazobactam and in trials comparing ertapenem and ceftriaxone were: diarrhoea (ertapenem versus piperacillin-tazobactam 5.0% versus 7.0%; ertapenem versus ceftriaxone 5.6% versus 5.9%); infused vein complications (ertapenem versus piperacillin-tazobactam 4.5% versus 7.9%; ertapenem versus ceftriaxone 3.2% versus 4.6%); nausea (ertapenem versus piperacillin-tazobactam 2.5% versus 3.4%; ertapenem versus ceftriaxone 3.4% versus 3.3%); and elevations in alanine aminotransferase levels (ertapenem versus piperacillin-tazobactam 8.8% versus 7.3%; ertapenem versus ceftriaxone 8.3% versus 6.9%). Most ertapenem-related AEs were reported as mild-to-moderate in intensity. Ertapenem was not associated with prolongation of the QTc interval. Local reactions of moderate-to-severe intensity at the infusion site were infrequent and occurred with similar frequency in the ertapenem and comparator treatment groups. No overall differences in safety were observed between elderly (aged > or = 65 years and > or = 75 years) and younger patients. Ertapenem, 1 g once a day given by intravenous infusion or intramuscular injection, was generally well tolerated and had overall safety and tolerability profiles similar to those of piperacillin-tazobactam and ceftriaxone.

Efficacy of ertapenem against methicillin-susceptible Staphylococcus aureus in complicated skin/skin structure infections: results of a double-blind clinical trial versus piperacillin-tazobactam

Staphylococcus aureus is the predominant pathogen in complicated skin/skin structure infections. In this analysis of a subgroup of data from a randomised, double-blind trial, the efficacy of ertapenem 1 g daily was compared with piperacillin-tazobactam 3.375 g Q6H for treatment of complicated skin/skin structure infections caused by methicillin-susceptible S. aureus (MSSA). Of the 529 treated patients in this trial, 185 (35.0%) had MSSA as a baseline pathogen. At the test of cure assessment 10–21 days post-therapy, 54 of 67 (80.6%) protocol evaluable patients in the ertapenem group and 55 of 68 (80.9%) in the piperacillin-tazobactam group were cured (odds ratio: 1.0 (95% confidence interval (CI): 0.4–2.4), P=0.99). In both treatment groups, cure rates were higher in patients with monomicrobial than polymicrobial infections, but the difference was not significant. In this subgroup analysis of patients with MSSA complicated skin/skin structure infections, therapy with ertapenem 1 g daily was as effective as piperacillin-tazobactam 13.5 g divided in four daily doses.

A prospective, randomized, double-blind multicenter comparison of parenteral ertapenem and ceftriaxone for the treatment of hospitalized adults with community-acquired pneumonia

Background: Ertapenem is a once-daily parenteral beta-lactam licensed in the United States in November 2001 and in Europe in May 2002. Objective: This study compared the efficacy and safety profiles of ertapenem with those of ceftriaxone for the treatment of hospitalized adult patients with serious community-acquired pneumonia (CAP) requiring parenteral therapy. Methods: In this prospective, double-blind (with sponsor blinding), multicenter study, adult patients with CAP were stratified by Pneumonia Severity Index (≤3 or >3) and age (≤65 or >65 years) and randomized (2:1) to receive IV or intramuscular (IM) ertapenem 1 g once daily or IV or IM ceftriaxone 1 g once daily. Investigators could switch patients to an oral antimicrobial agent if clinical improvement was shown after at least 3 days of parenteral therapy. Results: A total of 364 patients were randomized to treatment: 239 to the ertapenem group and 125 to the ceftriaxone group. Three patients in the ertapenem group and 2 in the ceftriaxone group did not receive study therapy. Of the treated patients, 77.1% (182/236) of patients in the ertapenem group and 75.6% (93/123) in the ceftriaxone group were clinically evaluable. Among clinically evaluable patients, the mean (SD) durations of parenteral and total (parenteral plus optional oral) therapy were 5.5 (2.6) and 11.5 (2.7) days for ertapenem and 5.6 (2.8) and 11.7 (3.0) days for ceftriaxone, respectively. Streptoccocus pneumoniae was the most frequently isolated pathogen in both treatment groups. Cure rates were 92.2% for clinically evaluable patients in the ertapenem group and 93.6% for those in the ceftriaxone group (95% CI for the difference, adjusted for stratum, −8.6 to 5.7), fulfilling the criteria for statistical equivalence. At completion of parenteral therapy, 94.7% of patients in the ertapenem group and 95.8% in the ceftriaxone group showed clinical improvement. Infused vein complications (ertapenem, 3.4% [8/236]; ceftriaxone, 7.3% [9/123]) and elevated transaminase levels (ertapenem, 6.3% [13/207]; ceftriaxone, 7.1% [8/113]) were the most common adverse events in both groups. Conclusions: In this study of hospitalized adult patients, ertapenem therapy, with an oral switch option, was as effective as ceftriaxone with the same oral switch option for treatment of CAP requiring initial parenteral therapy. The overall safety profiles of the 2 drugs were comparable.