Safety and Efficacy of Single Daily Dose of Ceftriaxone and Metronidazole for Treatment of Complicated Appendicitis in Children
Condition: Complicated Appendicitis
MeSH terms: Appendicitis
Study type: Interventional
Phase: Phase 4

Summary: 
      A prospective open randomized study conducted between July 1st 2008 and June 30th, 2009.
      Included were children younger than 14 years with Complicated appendicitis randomly assigned
      either to a single daily dose of Ceftriaxone and Metronidazole or Ampicillin, Gentamicin, and
      Metronidazole. The outcome variables compared were: maximum daily temperatures, overall
      duration of fever, time return to oral intake, length of antibiotic therapy, results of
      repeat WBC measure, general/intra abdominal complications, need for intra abdominal abscess
      drainage, Length of stay and adverse reaction.
    

Detailed description: 
      The study was conducted at the Pediatric Surgery Department at HaEmek Medical Center, Afula,
      Israel. Included were children age 1-14 years with complicated appendicitis that was defined
      by one of the followings: 1. Demonstration by abdominal ultrasound and/or computed tomography
      of appendix perforation and/or peri-appendicular abscess 2. Demonstration by abdominal
      ultrasound of free fluid, and signs of diffuse peritoneal irritation in the right lower
      quadrant of the abdomen 3. At surgery performed for suspected non complicated appendicitis.
      In a patient with perforate appendicitis that was diagnosed at surgery, appendectomy was
      performed by one of the 4 senior pediatric surgeons on call at the time of the child's
      admission. Exclusion criteria were: documented allergy to any of the study medications, acute
      or renal insufficiency at admission, and severe septic shock at admission.

      Therapeutic approach: After the diagnosis of complicated appendicitis was established,
      patients were randomly assigned to therapy with either once daily of ceftriaxone and
      metronidazole or ampicillin, gentamicin and metronidazole. Therapy was change to
      piperacillin/tazobactam in patients who were still febrile at day 7-10 of the admission (if
      not given before), based on the clinical situation, and in all febrile patients at 11 day of
      the admission . All patients had also been treats after inclusion with pain control
      medications, no oral food or fluid , and intravenous hydration as necessary. Nasogastric
      tubes were not used routinely. On the fifth admission day patients who were stable, a
      febrile, could tolerate diet and had Complete blood count within normal limits were
      discharged home with oral amoxicillin/clavulanate therapy for further 7 days.

      Follow-up at the admission: CBC and renal and liver function tests were obtained before
      starting the antibiotic treatment and repeated on day 4 in all patients. In the group treated
      with AGM, serum trough gentamicin concentration was drawn before the fourth dose with normal
      level considered as < 2 mcg/ml. Other blood studies were performed based on the discretion of
      the attending physician based on the patient's clinical status. For patients who were either
      febrile or had leukocytosis, at day 5 of therapy abdominal ultrasound was obtained to assess
      for the presence of an abscess. Patients in whom abscesses were delectated undergone per
      coetaneous drainage (when possible). The original antibiotic regimen was either continued or
      changed to piperacillin/tazobactam based on the clinical situation. Patients, in whom
      appendectomy had not been done at admission, were readmitted for appendectomy at 6 weeks. All
      patients had been followed for a year since the admission for signs of intra abdominal
      complication such: repeat abscess formation, repeat admission, obstruction etc.

      Data collection: Data were recorded were: patient's age, weight, gender, maximum daily
      temperature, duration of fever, results of complete blood count, renal and liver function
      tests, gentamicin levels (where applicable), intra abdominal complications and duration of
      hospitalization. The outcome variables included maximum daily temperatures for each of the
      first 10 postoperative days, time to initial oral intake, length of hospitalization, length
      of antibiotic therapy, abscess formation rate, need to change antibiotic regimen, wound
      infection rate, and any abnormal findings during the follow-up visits.

      Statistical analysis: Since data in the literature show that there is no difference of the
      length of stay in between the 2 regimens (in children with complicated appendicitis following
      operation), and most studies included relatively low number of patients, no power analysis
      was calculated. The difference between various parameters in the two treatment groups were
      assessed by 2 independent sample T tests or Fisher exact tests for categorical data and 2
      independent sample t test or the Mann Whitney test for continuous data. Descriptive
      statistics were calculated as mean ± SD.
    

Intervention name(s): ceftriaxone, metronidazole/ampicillin, gentamicin, and metronidazole
Intervention type(s): Drug
Intervention MeSH terms: Metronidazole; Gentamicins; Ceftriaxone; Ampicillin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: complicated appendicitis; Children; conservative therapy; Study population: Children 1 month - 14 years with Complicated appendicitis; Type of the study: prospective, open randomized