Antibiotics as First-line

Therapy for Acute

Appendicitis: Evidence
for a Change in Clinical
Practice
Jeanette Hansson Ulla Korner Karin Ludwigs
Erik Johnsson Claes Jonsson Kent Lundholm
Published online: 9 May 2012
Societe Internationale de Chirurgie 2012

Nurul Mazni Abdullah

112012230
Pembimbing: dr Romzi K. spB

Abstract
Background : Randomized studies have indicated that
acute appendicitis may be treated by antibiotics without
the need of surgery. However, concerns have been
raised about selection bias of patients in such studies.
Therefore, the present study was aimed to validate
previous findings in randomized studies by a full-scale
population-based application.
Methods : All patients with acute appendicitis at
Sahlgrenska University Hospital (May 2009 and February
2010) were offered intravenous piperacillin plus
tazobactam according to our previous experience,
followed by 9 days out-hospital oral ciprofloxacin +
metronidazole. Endpoints were treatment efficacy and
complications. Efficient antibiotic treatment was defined
as recovery without the need of surgery beyond 1 year
of follow-up.

Results : A total of 558 consecutive patients were

hospitalized and treated due to acute appendicitis. 79%
(n=442) received antibiotics as first-line therapy and 20 %
(n=111) had primary surgery as the secondline therapy.
77% of patients on primary antibiotics recovered while 23
% (n=100) had subsequent appendectomy due to failed
initial treatment on antibiotics. 38 patients (11 %) of the
342 had experienced recurrent appendicitis at 1-year
follow-up. Primary antibiotic treatment had fewer
complications compared to primary surgery.
Conclusions: This population-based study confirms previous
results of randomized studies. Antibiotic treatment can be
offered as the first-line therapy to a majority of unselected
patients with acute appendicitis without medical
drawbacks other than the unknown risk for long-term
relapse, which must be weighed against the unpredicted
but well-known risk for serious major complications
following surgical intervention.

Pendahuluan
Appendisitis akut adalah kelainan surgikal tersering
4 randomized controlled trials telah dilakukan bagi
membandingkan antibiotika dengan appendektomi
menunjukkan hasil yang sama 88-95% initial
recovery pada terapi antibiotik
Rekurensi pada penelitian sebelumnya 10-15% setelah
1 tahun pasien diterapi dengan antibiotik + komplikasi
mayor < (abses, reoperasi, obstruksi usus halus)
Studi yang pertama pada pasien 18-50 tahun, hanya
20% pasien yang layak validitas dan generalitas
rendah

Metode
Prospective nonrandomized population-based
study

Material
Subjek :
558 pasien dirawat ec appendisitis akut. (0.10-0.12%
dari populasi 575000-600000)
Prestudy 18% perforasi, 82% nonperforasi pada
operasi

Kriteria inklusi :dewasa >16 tahun dengan

appendisitis akut berdasarkan anamnesa, status
abdominal, tes laboratorium, pemeriksaan
radiologi (jika meragukan), mendapat antibiotika
sebagai terapi lini pertama
Kriteria eksklusi : Pasien yang diterapi di luar

 Waktu : May 2009 and February 2010

Lokasi : surgical clinics of Sahlgrenska
University Hospital/Sahlgrenska and
Sahlgrenska University Hospital/Ostra

Intervensi
Antibiotik diberi sebagai terapi lini pertama, namun tergantung
ahli bedah apakah perlunya dioperasi atau APS
Gagal terapi antibiotik dilihat dari
Progression status abdomen
Peningkatan suhu tubuh
Tidak ada pembaikan dalam 12-24 jam

Mereka yang hamil atau appendisitis rekuren appendektomi

Piperracillin +tazobactam 4g/8 jam minimal 3 dosis dalam 24
jam. Nir oral + cairan intravena.
Status klinis >> (> 12-24 jam) pulang + antibiotik
(ciproflxacin 500mg dan metronidazole 400mg 2x/hari) sebagai
tambahan untuk 9 hari

Pengumpulan data
Data pre, peri dan post-terapi dicatat berdasar
protokol
Ahli bedah menilai status abdominal dan alasan
untuk operasi bila perlu
Questionnaires - gejala sisa dan sakit perut,
pengalaman dirawat di rumah sakit sebelumnya,
apa saja operasi atau pengobatan relevan
tambahan didapat
Data medis rumah sakit bagi tiap pasien dicari
minimum 1 tahun setelah terapi dan dicari apakah
adanya komplikasi, rekurensi dan reoperasi

Analisis statistik
Tes chi square perbedaan antara proporsi
t-test membandingkan variable antara
kelompok
p<0.05 two-tailed test signifikan
SPSS versi 17.0 digunakan

Outcome measures
Primary endpoints : effektivitas terapi dan
komplikasi mayor.
Terapi antibiotik effisien : Pemulihan tanpa perlunya
operasi bagi pertama kali dirawat inap di rumah
sakit dan follow up hingga 1 tahun tanpa rekurensi
Terapi operasi dianggap efisien jika ada temuan
positif pada eksplorasi (appendisitis atau diagnosis
surgikal lain). Temuan negatif surgical failure
Secondary endpoint : komplikasi minor, durasi
dirawat di rumah sakit, pada follow-up adanya nyeri
perut atau perut tidak nyaman.

Hasil

50%

32%

20%

79%

23%
77%

11%

 Patients who received primary surgery had significantly higher

white blood cell counts (WCC) and more local or general
peritonitis.
Patients who successfully recovered on antibiotics alone had
significantly lower WCC, neutrophils, and temperature than
patients who failed to improve with primary antibiotics

 Primary antibiotics
77 % successful recovery
Treatment efficacy
23 % had subsequent rescue
appendectomy
11 % recurrent appendicitis
33 appendectomy
6 2nd round of antibiotics 1
didnt recover appendectomy

The same diagnostic criteria were

used for patients with recurrent
abdominal pain as for patients at
first admission for abdominal
pain.

Primary surgery
88 % appendicitis /surgically
curable diagnoses.
12 % were negative explorations.
92% extirpated appendices were
sent for histopathology (PAD)

 The proportions of
phlegmonous,
gangrenous, and
perforated
appendicitis did
not differ between
patients who had
primary surgery
and those who
had rescue
surgery

Major complications within the 1-year follow-up did not differ

significantly
Abscess formation was the most common complication.
In the antibiotics group, 6 patients were later operated on because
of suspected appendicitis (diagnostic laparoscopy or open
appendectomy) without any positive findings, i.e., it was an
unnecessary operation by protocol.

2x with primary
surgery
3x antibiotics failure
>success primary
antibiotics.
The most common
complications among
operated patients
were prolonged
postoperative course
(vomiting, intestinal
paralysis) and wound
infection, and among
antibiotics-treated
patients, the most
common complication
was some side effect
of the antibiotics
(mainly diarrhea).

Patient experience
Abdominal discomfort after 6 and 12 months
did not differ between the antibiotics and the
surgery group after 12 months 27 %
abdominal symptom(+)
Based on questionnaire answers from 411
(74 %) patients at 6 months
382 (69 %) patients at 12 months.
The proportion that answered the
questionnaire was similar in both groups

Duration of antibiotic
therapy
First-line antibiotics = intravenous antibiotic
(primary surgery with subsequent
perioperative antibiotics) (1.60.2 days).
Primary antibiotics failure appendectomy
2.30.1 days compared to those who
recovered on primary antibiotics alone, as
expected (p\0.001).

Hospital stay
Primary antibiotics (2.3 0.1 days) <primary
surgery (2.90.3;p\0.025).
Primary antibiotics operation
(3.60.2days) >primary antibiotics alone(1.9
0.1 days; p\0.001)

Diskusi
>75% pasien dengan appendisitis akut sembuh dengan terapi
antibiotika tanpa perlunya operasi
Amoxicillin dan asam klavulanat cukup untuk infeksi GIT
Juga tidak ada perbedaan signifikan pada komplikasi mayor
pada pasien yang pulih sepenuhnya dengan antibiotika primer
dan mereka yang mendapat appendektomi rescue seterusnya
Komplikasi minor 2x lebih banyak pada pasien yang mendapat
operasi primer dan proporsi pasien yang mengalami
abdominal discomfort antar 6-12 bulan tidak berbeda
Kebanyakan pasien dewasa boleh diterapi awal dengan
antibiotik pada 12-36 jam pertama tanpa ada persoalan untuk
operasi akut seperti generalized peritonitis, sepsis sistemik
dan tanda disfungsi vital lain

Kesimpulan
Studi population-based mengkonfirmasi hasil
randomized studies sebelumnya.
Terapi antibiotika sebagai terapi lini pertama
boleh diberikan pada mayoritas pasien
appendisitis akut tanpa medical drawbacks
selain dari risiko yang diketahui untuk relaps
jangka lama, yang harus dipertimbang
dengan risiko komplikasi mayor yang tidak
dapat diprediksi tapi sedia diketahui setelah
intervensi bedah

Thank you