Safety and tolerability of ertapenem versus ceftriaxone in a double-blind study performed in children with complicated urinary tract infection, community-acquired pneumonia or skin and soft-tissue infection

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Abstract

The carbapenem antibiotic ertapenem has been shown to be safe, well tolerated and effective in treating adults with complicated urinary tract infection, skin and soft-tissue infection and community-acquired pneumonia. In this study, we evaluated ertapenem for treating these infections in children in a randomised, double-blind, active-controlled clinical trial. The primary outcome was the incidence of clinical and laboratory drug-related serious adverse events (AEs). Children were randomised in a 3:1 ratio (ertapenem:ceftriaxone) stratified by index infection and age to receive ertapenem or ceftriaxone; 303 children received ertapenem and 100 children received ceftriaxone. The median duration of parenteral therapy was 4 days for both treatments. The most commonly reported drug-related clinical AEs during parenteral therapy were diarrhoea (5.9% ertapenem, 10% ceftriaxone), infusion site erythema (3% ertapenem, 2% ceftriaxone) and infusion site pain (5% ertapenem, 1% ceftriaxone). One child in each group reported a serious drug-related clinical AE. No serious drug-related laboratory AEs were reported. In children aged 3 months to 17 years, ertapenem was well tolerated and had a comparable safety profile to that of ceftriaxone.

Introduction

Ertapenem is a group I carbapenem [1] with broad-spectrum antibacterial activity against aerobic and anaerobic pathogens, excluding meticillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas and Acinetobacter spp. Ertapenem has a high degree of in vitro activity against targeted Gram-negative and Gram-positive pathogens [1], [2], [3], [4] and is active in vitro against extended-spectrum β-lactamase-producing Klebsiella pneumoniae and Escherichia coli[5]. Ertapenem is safe and effective for adults with complicated intra-abdominal infection (cIAI), acute pelvic infection, complicated urinary tract infection (cUTI) and skin and soft-tissue infection (SSTI), including diabetic foot infections [6], and community-acquired pneumonia (CAP) [7]. It is also effective as prophylaxis for surgical site infections following colorectal surgery [8]. A recent study demonstrated the safety and efficacy of ertapenem for treating children with cIAI and acute pelvic infection where mixed infections are expected, and ertapenem offers a simplified regimen with the possibility of intramuscular dosing [9].

Section snippets

Study design

This randomised, double-blind, active-controlled trial, conducted at 39 international centres during 2002 and 2003, evaluated the safety, tolerability and efficacy of ertapenem versus ceftriaxone for treating children with cUTI, SSTI or CAP. Written informed consent was obtained for each patient from the legal guardian. The study was registered with ClinicalTrials.gov (Identifier: NCT00451386).

Patients

Children aged ≥3 months and <18 years with cUTI, SSTI or CAP requiring initial parenteral antibiotic

Patient accounting and demographics

Of 451 participants screened for enrolment, 47 (19 with CAP, 25 with SSTI and 3 with cUTI) were not randomised (Fig. 1). Of the 404 participants randomised, 304 were randomised to the ertapenem group and 100 to the ceftriaxone group. One child randomised to the ertapenem group did not receive any study drug (and is therefore not included in the safety analysis) and one child randomised to the ceftriaxone group withdrew consent (included in the safety analysis but not included in Table 1 as no

Discussion

This randomised, double-blind, active comparator study of 403 paediatric patients with cUTI, SSTI or CAP is, to our knowledge, the largest such study of a parenteral antibacterial in children to date. The double-blind design minimised the potential for bias, particularly in the assessment of clinical safety. These results extend the available data on ertapenem for treatment of moderate-to-severe cUTI, SSTI and CAP in a paediatric population and are consistent with the results obtained for these

References (15)

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Cited by (0)

ClinicalTrials.gov identifier: NCT00451386.

1

Other members of the Protocol 036 Study Group are: Margarita Ardila, Colombia; Antonio Arrieta, USA; Parvin Azimi, USA; John Bradley, USA; Archana Chatterjee, USA; Milan Cizman, Slovenia; William Clark, USA; Joseph Domachowske, USA; Maria Isabel Galaz, Chile; Raquel Garces, Peru; Maria Garcia de Miguel, Spain; Adrian Georgescu, Romania; Deidre Hahn, South Africa; Martinus Heystek, South Africa; Mia Koh, Malaysia; William La Via, USA; Walter Ledermann, Chile; Jay Lieberman, USA; Chitra Mani, USA; Carmen Otero Reigada, Spain; Ana Rodrigues, Brazil; Adib Rodriguez, Guatemala; Judith Rowen, USA; Raul Rudoy, USA; Jesus Ruiz-Contreras, Spain; Venusto SanJoaquin, USA; Libia Segura, Colombia; Renato Stein, Brazil; Jose Suarez, Venezuela; Desamparados Perez Tamarit, Spain; Kah Tan, Malaysia; Petra Thürmann, Germany; Jacobus Van Dyk, South Africa; Rosa Velasco-Bernardo, Spain; Hui Kim Yap, Singapore; and Stefan Zielen, Germany.

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