Safety and Efficacy of Single Daily Dose of Ceftriaxone and Metronidazole for Treatment of Complicated Appendicitis in Children
Safety and Efficacy of Single Daily Dose of Ceftriaxone and Metronidazole for Treatment of Complicated Appendicitis in Children
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.
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.
Inclusion Criteria:

 -  Children age 1-14 years CA that was defined by one of the followings:

 1. Demonstration by abdominal ultrasound (US) and/or computed tomography (CT) of
 appendix perforation and/or peri-appendicular abscess

 2. Demonstration by abdominal ultrasound (US) of free fluid, and signs of diffuse
 peritoneal irritation in the right lower quadrant of the abdomen 3

 Exclusion Criteria:

 -  Documented allergy to any of the study medications, acute or renal insufficiency at
 admission, and severe septic shock at admission.