Monotherapy versus triple therapy antibiotics for the management of perforated appendicitis in children

Monotherapy versus triple therapy antibiotics for the management of perforated appendicitis in children

Mohamed  E Hassan, MD

Associate Professor of Pediatric Surgery, Zagazig University, Egypt.

Introduction:  Appendicitis  is  the  most  common  surgical  emergency  in  the  pediatric population.  Despite  the  widespread  prevalence   of  the  disease,    there  is  little  consensus regarding the diagnosis and management  of appendicitis.  The aim of the study is to compare the surgical outcome  of laparoscopic  appendectomy  in  children  for perforated  appendicitis using perioperative triple versus a single antibiotic based regimen.

Patients  and  methods:   A retrospective review  was done  for all the  children  who had  a laparoscopic appendectomy  for perforated appendicitis in a tertiary pediatric surgery center in UAE in the period  from June 2009 to January 2014. A total of 56 children was included in the study  Group A, monotherapygroup 'MG' (31 cases) who were managed with  piperacillinl tazobactam  and  group  B,  triple  therapy  group   'TG'  (25  cases)  who  were managed  with Amoxicillin Clavulanate, Metronidazole and amikacin.

Results:  There were 52% males and 48%  females, mean age were 8.3 ± 1.5 years.  There were 26% cases versus 28% cases in MG and TG respectively  who required more than 7 days antibiotics. Mean  total length of hospital  stay was  statistically  significant more in TG than MG. There was significant difference between both groups (13% versus 36% in MG and TG respectively)  for the need to replace the IV cannula before 72 hours.

Conclusion: Monotherapy antibiotic management  of perforated appendix in  children was equally effective as triple antibiotic therapy in the current study population  for the infectious morbidities. Monotherapy antibiotic management  showed significant less incidence of intravenous  cannula morbidities and shorter total hospital stay

Key words: Appendix, laparoscopy, children, antibiotics.

Introduction:

Appendicitis is the most common surgical emergency  in  the  pediatric  population. Despite the widespread prevalence of the disease, there is little consensus regarding the diagnosis and management of appendicitis.!

Although  many  physicians  would  argue that "standard therapy" consists of an aminoglycoside, a B -lactam, and an antibiotic with anaerobe coverage (ie, ampicillin, gentamicin, or metronidazole),2-5 These medications are individually inexpensive; however, each is administered multiple times per day, creating a complex dosing schedule. Gentamicin is an aminoglycoside with known renal  and ototoxic  side effects that requires the measurement  of serum levels.  Although

this regtmen has been safe and reliably effective, contemporary antibiotics allow a large selection of drugs that do not require laboratory monitoring.6

Increasing      evidence      suggests      that single-agent antibiotic therapy provides equivalent results, compared with multiagent regimens.7-9

The   aim  of  the   study   is  to   compare the surgical outcome of laparoscopic appendectomy in children for perforated appendicitis using perioperative triple versus a single antibiotic based regimen.

Patients and methods:

A  retrospective   file  revtew   was   done for  all the  children  who  had a laparoscopic

appendectomy   for   perforated   appendicitis in a tertiary governmental pediatric surgery center in UAE in the period from June 2009 to January 2014.

Exclusion  criteria  included  children  who had conversion to open appendectomy and children who received another antibiotic reg1men.

A total of 56 children was included in the study. Patients were divided into two groups, according to the type of antibiotic regimen used, Group A, monotherapy group 'MG' (31 cases) who were managed with piperacillin/ tazobactam and group B, triple therapy group

'TG' (25  cases)  who  were  managed  with

Amoxicillin Clavulanate, Metronidazole and amikacin.

The following data were collected, patient

demographics,  pre and  postoperative  white blood  cell  count  (WBCs)  and  C  reactive protein (CRP), preoperative and postoperative fever   (the   mean   of  the   daily   maximum temperature),   operative  time,  intraoperative findings        (generalized     versus   localized peritonitis), the total  length of hospital stay, surgical  site  infection  (SSI),  postoperative residual  intraperitoneal  collection,  need  to replace the  intravenous  (IV) cannula  before

72 hours and 1 month follow up results.

Data were collected, tabulated and statistically   analyzed  using  SPSS   17.  Chi square  (for  qualitative  data)  and t test  (for quantitative   data)  were   calculated  to  test for the significant differences between the groups, P< 0.05 was considered as statistically significant difference.

Perioperative management:

Diagnosis    of    appendicitis    was    done based on clinical,  laboratory and abdominal ultrasound  findings,  CT  scan  was  done  in very selected cases of doubtful diagnosis. All the cases received a single dose preoperative Amoxicillin Clavulanate within 30 minutes before surgery.

Surgical   procedure   were   standard   for

all the  cases. 3 ports were used,  umbilical, suprapubic and left iliac fossa. Mesoappendix was divided with monopolar  diathermy  and the  base  of  the  appendix  was  ligated  with

absorbable endoloop (EL, 2/0 polydioxanone PDS, Ethicon Endosurgery, Inc. Cincinnati, OH, USA), the appendix was retrieved from the umbilical port.

Perforated    appendix    was    defined    as an    appendix    found    intraoperatively    to have  a  hole,  the  hole  was  not  iatrogenic during surgery. Gangreanous appendix was considered as perforated appendix.

Residual   intraabdominal   collection  was

defined as any postoperative intraabdominal collection after surgery diagnosed by ultrasound associated with fever and aspirated fluid was positive for the culture.

Surgical site infection was defined as any

discharge from any ofthe wounds within one month of surgery associated with redness, tenderness and/or fever.

CRP and WBCs were repeated on the 3rd

and  5th postoperative  days. Patients were discharged when the CRP was less than 20, decreasing  WBCs  and  there  was  no  fever for 24 hours without the use of antipyretic medications.   If  CRP  was  still  high  and  I or WBCs not decreasing (Regardless of the temperature scale), antibiotics were continued for more 3 days then investigations repeated, if  it  was  still  high,  Ultrasound  and/or  CT scan was obtained and managed accordingly. Patients   were  reviewed   in  the   outpatient clinic 1 month after discharge.

Piperacillin/tazobactam       dose     was      80

mg/kg/dose    8  hourly   (maximum   4   gm/ dose),  Amoxicillin   Clavulanate   30  mg/kg/ dose 8 hourly (maximum  1.2 gm/dose), Metronidazole    10  mg/kg/dose   (maximum

500 mg/dose) and Amikacin 7.5 mg/kg/dose

every 12 hours. All the intravenous cannulas were changed every 72 hours of insertion according to our hospital policy.

Results:

There was 29 (52%) males and 27 (48%) females in the study, mean age in the study was 8.3 ±1.5 years, Table (1).

The  mean  values  of the temperature  for both  groups  are  illustrated   in  Figure (1). Details of the mean WBCs count and CRP values pre and postoperatively  is shown in Figures (2,3)  respectively.  Mean  operative  

38.8

38.5

38.2

37.8

37.5

37.2

36.8

36.5

I • MG_._ L_G_j

Figure (I): Mean values of pre and postoperative temperature  for both groups.

20000

15000

I + MG .. TG   I

10000

5000

0

Preoperatively           3rd day postoperatively   5th day postoperatively

Figure (2): Pre and postoperative  values of the mean WBCS for both groups.

200

150

100

50

0

Preoperative                   3rd day Postoperative            5th day postoperative

Figure (3): Pre and postoperative mean CRP values for both groups.

Table 1: Demographics for both groups.

Table 2: Variables in both groups.

time   for  MG  was  45±10  minutes  versus

52±20 minutes for TG (t =1.7, P > 0.05).

There were 8 (26%) cases versus 7 (28%) cases in MG and TG respectively required more than 7 days ofiVantibiotics (X2= 0.034, p >0.05).

Table (2) shows variables in both groups, there was one case in TG case of adhesive bowel obstruction that required adhesiolysis.

Discussion:

Appendicitis     1s    the      most     common indication   for   urgent        abdominal   surgery in  the   pediatric   population,   and  ruptured appendicitis   affects  a  large  proportion   of those patients.lO Minimizations of morbidity, cost, hospital length of stay, and readmissions remain     primary     objectives     of    surgical management.            Postappendectomy                infection relates to all of these measurable  outcomes, and the choice  of antibiotic  regimens  has a major  effect on each  of these  parameters.lO

Almost 60% of surgeons  base their  clinical practice  in  the  management  of  perforated appendicitis on their individual preferences.ll There   was      no        statistically   significant differences in the gender and age between both groups.  TG  showed  statistically  significant more weight, which is expected due to older

mean age for the TG than MG.

There is grade B evidence that the length of  administration  of  IV  antibiotics  should be based on  clinical  criteria,  such as fever, pain,  return  of  bowel  function,  and  white blood cell (WBC) count.l2,13 In the  current study, temperature scale showed that MG reached the  normal  range (37.2  °C)  on the 4th  postoperative   day,  while  for  TG  the mean  temperature  was  37.3  oc on the  5th postoperative  day. The WBCs scale was almost  similar  for  both  groups,  while  the CRP scale showed more sloping  decrease in the MG than TG.

Although     26%    versus     28%    in    MG and  TG  required  antibiotic  regimen   more than 7 days, which  didn't reach  statistical significant  difference, there  was  statistically significant  more  mean  time  of total  hospital stay for TG than  MG.  In concordance to the current   study,   Adam   et   ailO  retrospective study    of   8545    children    showed    longer hospital  stay in the triple antibiotics group (aminoglycoside based combination therapy) than   monotherapy  group   (Ceftriaxone or Piperacillin/ tazobactam). Nadler et al9 didn't show   significant    differences  between    the study groups  regarding the length of hospital stay.

Intraoperative       findings,       SSI       and postoperative        residual         intraperitoneal collection didn't reach statistically significant differences between both groups in the current study. In contrary, Nadler  et al9 showed significantly higher  postoperative infectious complications in the multiagent antibiotics group than Piperacillin/ tazobactam group.

In accordance to Nadler  et al,9 there  was statistically significant  difference between both groups  (13% versus 36% in MG and TG respectively) for the  need  to  replace  the  IV cannula  before  72  hours,  which  is attributed to the occurrence of thrombophlebitis due to frequent injections.  As IV  cannula  insertion is   very    annoying    procedure   in   children, even with the use of local anesthetic during insertion, we think venous  access morbidities should be always looked for in planning antibiocs  management in children.

The  down  side of the current  study  is the small  number  of the study  population and  it is a retrospective study.  But it highlighted several findings that it will be of value to be studied  in a prospective well designed study with larger population.

Conclusion:

Monotherapy antibiotic management of perforated appendix  in children  was equally effective  as triple antibiotic therapy  in the current study  population for the infectious morbidities. Monotherapy antibiotic management  showed  significant   less incidence of intravenous cannula  morbidities and shorter total hospital stay.

Reference:

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