Background:

- Clinical dx not accurate enough and imaging indicated

- Sx Triad: pain LLQ, absence of vomiting, CRP >50.
o Fever, wbc, LLQ pain
- If imaging indicated (no triad sx): CT only after negative or inconclusive
US
- Based on hx, PE, CT scan triaged to outpatient vs inpatient
- DIVER trial: outpt vs inpat. 132 pts. Similar failure rate and QOL.
-
-
Introduction:

- Acute diverticulitis:
o Natural hx is mild.
o Most pts can be treated with conservative measures
IVF, abx, restricted diet, pain control
o 2 retrospective comparative studies & 1 RCT (5,6, 7)
abx tx not more successful
Length of stay, complications, readmission
o Guidelines (8-10)
o Countries and guidelines (11-13)
- Key messages.
o Population: acute uncomplicated diverticulitis confirmed by CT scan
o Intervention: broad spec abx at least 7 days
o Comparison: no abx
o Outcome: May not improve symptom resolution. But may decrease risk of
recurrence and diverticular complications in comparison to no abx.
o Low quality of evidence

Methods
- DIABOLO
o RCT: uncomplicated acute diverticulitis

-
 - Setting and participants
o Eligibility:
1st episode, left-sided, uncomplicated, confirmed w/in 24h
by CT
Hinchey Stages 1a-b
Ambrosetti mild
o Exclusion:
Radiologically proven (us, or ct) diverticulitis
Higher stages
Abx use past 4 weeks
Terminal disease (<6mo)
Pregnant, breastfeeding
CI to abx
ASA >III
Immunocompromised
Septic
- Randomization & Interventions
o Computerized system
o Stratified by Hinche classification and center
o Dutch abx policy committee & American Society of Colon and
Rectal Surgeons
Amox-clavulanic acid (broad spec)
10 days: IV (1200mg QID @least 48h) -> PO 625mg tid
For allg: Cipro + flagyl
o Abx tx admitted inpt IV
o Conservative
Outpatient if: PO diet, <38C, VAS <4, self-support
Started on abx if: >39C, + bcx, sepsis
Outcomes and follow-up
- Outcome
o Primary outcome: Time to recovery during 6mo of f/u
Full recovery: d/c, nl diet, T <38C, pain <4, pre-illness
activity lvl 19 d
o Secondary outcome:
days spent outside hospital in 6mo
readmission rate
complication (abscess, pef, obstxn/strict, diverticular
bleed/fistula)
ongoing diverticulitis
recurrence of diverticulitis
sigmoid resection or surgical intervention 6-12mo
abx sfx
F/u:
adherence to abx done by telephone. (?freq)
 2 & 6mo (clinic)
12 & 24mo (telephone)
- Statistical analysis
o Post hoc power analysis
Difference in time to recovery of more than 5days in 180d
(6mo) f/u
Hazard ratio 0.706: 17d obs, 12 days abx
o Primary outcome (Kaplan Mieir time to recovery curves plotted
and median times reported)
o
- Results
o June 2010 October 2012
o Population:
893 pts in 22 Dutch centres
323 excluded 570 assigned randomly [283 obs, 287 tx]
39 wrongly included and not eligible to participate
(262 obs, 266 abx) 528
o VAS score
Declined rapidly for both w/in 10 days from admission
No difference in VAS pain score over time
o Study tx
265/266 received abx
augmentin prescdribed 250/265 (94.3)
duration 10 days , 94.7% completed
3 pts (1.1) d/c abx 2/2 sfx or allg rxn (anaphylactic shock in
1).
Incorrectly stopped abx in 11
o Rate of + BCx: 0.285
5.9% obs
2.8% abx
o C diff toxin test: 22 total
14 obs
8 abx

o Time to recovery: Median

14 days obs; 12 abx tx
Hazard ratio for full recovery 91%
Hinchey & center adjustment HR 90%
Hinchey- HR 88%

Secondary outcomes
- 6 mo:
 o fulfilled recovery criteria
234 in obs
248 abx
o outpt tx
13% obs
0.4% abx
o duration of hospital
2 days obs
3 days abx
o Readmission rates
17.6% obs
12% abx

Discussion
- duration of initial admission longer & and abx-related adverse evetns
higher in abx group
- 3 previous studies demonstrate abx better but guidelines unchanged
because methodology
o 40% pts had recurrent rather than priary diverticulitis
o long accrual period
o no standardized abx tx
- limitations
o accrual rates different between centres (selection bias)
o errors: could not exclude pts with undetected first occurance due
to : episode without medical care or tx by general practicioner
without definitive dx
o possibility of type II error higher in obs due to multiple endpoints
o Lacked power to detect smaller subgroup effects
o Hinchey 1B studies limited (power small)

Evidence:
- Signle center randomized trial from Finland &
- Observation report from the same

Good:
- Standardized abx
- End points: Good and Bad
o time to recovery
o secondary outcomes relating to complications and recurrence
-
o Key messages. In patients with acute uncomplicated diverticulitis
confirmed by CT scan, treatment with broad-spectrum antibiotics for at
 least 7 days may not improve symptom resolution. However, antibiotics
may decrease the risk of recurrence and diverticular complications in
comparison with no antibiotics. The effect of antibiotics on the
development of sepsis and the need for surgery or colostomy is uncertain.
(Low quality of evidence)
o
o
- Pts who developed complications were started on abx and
management upgraded
o
-
Bad:
- confounding limitations
o 8% more of abx cohort suffered from mild or severe comorbid
disease (higher ASA)
- age group >40 yo (diverticulosis --- 40% are <40, >60% are > 70).
Discussion:
- Primary outcome: no difference. However 13% managed as outpatient
for obs
- Secondary: few statistical difference. , small magnitude in harm
relating to obs
o Ongoing diverticulitis w/in 6 mo
o Need for sigmoid resection
o Hospital re-admission
o Morbidity favored obs cohort (due to abx related adverse effects)
- Diverticulitis is an inflammatory rather than an infectious state

- Previous trials
o 10 centers in Sweden and Iceland and included 669 patients

o AVOD : swedent 2012. Randomized, open, multicenter

IV fluids, vs IVF and abx
Resutlts
Same hospital stay (few days)
Same at 6mo
10
o DIABOLO : randomized trial at multicenter DUTCH population,
2014
IVF or IV ABx
#528pts
Results:
No abx: more tx as outpatient, fever in hosp stay
o Same authors as AVOD
Changes at 2 of the hospitals in prior research
 Qualify: clinical sx and CT confirmed dx of uncomp diverti

Excluded: IC, pregn, sever pain or vomiting, poor

compliance risk
# 155.
o American Gastroenterological Association:
December 15: selective abx strategy for acute,
uncomplicated diverticulitis is reasonable
o Assessment:
Fascinating but WEAK
GRADE classification of quality of evidence is low.
AVOD: suffers from risk of bias
DIABOLO: presented only in oral abstract form
Observation: bias and lack of cohort control
- Randomized clinical trial of antibiotics in acute uncomplicated diverticulitis. AVOD 2012
- results of this study cannot necessarily be generalized to patients who are admitted for
diverticulitis because of complications, severe disease (eg, immunocompromised
patients, high fever, significant leukocytosis), or because they failed outpatient therapy.
In addition, these results are not applicable to outpatient therapy of acute diverticulitis,
as all participants were admitted to the hospital and given intravenous fluids.

- Criteria for inpatient treatment

Immunosuppression

- High fever (>102.5F/39C)

- Significant leukocytosis

- Severe abdominal pain

- Advanced age

- Significant comorbidities

- Intolerance of oral intake

- Noncompliance/unreliability for return visits/lack of support system

- Failed outpatient treatment

 Retrospective Comparative Studies

Hjern F, Josephson T,Altman D, Holmstrm B,Mellgren A, Pollack J etal.Conservative treatment of

acute colonic diverticulitis: are antibiotics always mandatory? Scand J Gastroenterol 2007; 42:41
47. 2007
o 311 pt
De Korte N, Kuyvenhoven JP, van der Peet DL, Felt-Bersma RJ, Cuesta MA,Stockmann
HB. Mild colonic diverticulitis can be treated without antibiotics. A casecontrol study. Colorectal
Dis 2012;14: 325330.

RCT
Chabok A, Phlman L,Hjern F, Haapaniemi S,Smedh K; AVOD Study Group. Randomized clinical
trial of antibiotics in acute uncomplicated diverticulitis. Br J Surg2012; 99: 532539. 2012
- Population: 10 center (Sweden and Iceland) = 623 pts (314w, 309 w/o)
- Method: w/o abx (IVF) and w/abx (IVF abd abx @ least 7d). ALL admitted
- Results:
o Complication (abscess, perf): # of pts --- 6 w/o vs 3 w/abx
o Median hospital stay: 3 days both
o Readmission for recurrent diverticulitis @ 1 year : similar 16%
- Conclusion:
o Abx doesnt accelerate nor prevent complication/recurrence
- Flaws:
o Predominantly women (2/3rd), ave age 57
o 40% had previous episode of diverticulitis
o abx varied: (2nd or 3rd gen cephalosporin )+ flagyl or carbapenem or zosyn
o w/ improvement PO (Cipro or cefadroxil) + flagyl

- Quality of evidence :
o Low:
Un-blinded
 Sequence of randomization not well concealed
Only 623 out of 669 randomized pts actually reported
Imprecision: small number of events

Abstract

Unl C, de Korte N,Daniels L, Consten EC,Cuesta MA, Gerhards MFetal.; Dutch Diverticular
Disease 3D Collaborative Study Group. A multicenter clinical trial investigating the cost-effectiveness
of treatment strategies with or without antibiotics for uncomplicated acute diverticulitis (DIABOLO
trial). BMC Surg 2010; 10:23. 2010
- Population: 528pts, Netherlands, first occurrence AUD
- Method: obs or 10d abx
- Results: No different in time of
o resultion of sx
o complications
o hospital duration
o risk of recurrence
- Conclusion:
- Flaws:
- Quality:
o Low: only in abstract from
o
Supporting Abx
Diverticulitis. Danny O. Jacobs, M.D., M.P.H.
N Engl J Med 2007; 357:2057-2066November 15, 2007DOI: 10.1056/NEJMcp073228

Recent hypothesis shift

M.H. Floch. A hypothesis: is diverticulitis a type of inflammatory bowel disease?
J Clin Gastroenterol, 40 (suppl 3) (2006), pp. S121S125

National guideline Changes:

Despite the relatively low quality of these new trials, several national health systems in Europe have
moved away from the obligate use of antibiotics for AUD: (i) The Danish Surgical Society has concluded
that antibiotics are not routinely recommended,5 (ii) a working group from The Netherlands recommended
that antibiotics not be routinely administered,6 (iii) an Italian consensus report found that antibiotics may
not improve outcomes but should be used on a case-by-case basis, 7 and (iv) a multidisciplinary German
group recommended that antibiotics be omitted in patients without risk factors for complicated disease but
only with close monitoring.8

Hinchey Modified Hinchey

0 Mild clinical diverticulitis

1a Colonic wall thickening/Confined peric

I Pericolic abscess or phlegmon
inflammation
 Hinchey Modified Hinchey

Ib Confined small (< 5 cm) pericolic absce

II Pelvic, intraabdominal, or retroperitoneal II Pelvic, distant intraabdominal, or retrope

abscess abscess

III Generalized purulent peritonitis III Generalized purulent peritonitis

IV Generalized fecal peritonitis IV Fecal peritonitis

Published guidelines and practise parameters

Antibiotics Original Which Original Original

Route of
Organization Year research research research
administering
Recommended cited antibiotics cited cited

Oral or
Covering both
American College of Kellum intravenous,
1999 Yes None Gram negative None
Gastroenterology[23] [15] depending on
and anaerobes
clinical status

European Association 1999 Yes None Ciprofloxacin None Oral or None

for Endoscopic intravenous,
Surgery[25] And depending on
 Antibiotics Original Which Original Original
Route of
Organization Year research research research
administering
Recommended cited antibiotics cited cited

Metronidazol clinical status

Oral or
American Society of Covering both
Kellum intravenous,
Colon and Rectal 2006 Yes None Gram negative None
[15] depending on
Surgeons[24] and anaerobes
clinical status

Oral or
Society of Surgery of Broad
intravenous,
the Alimentary 2007 Yes None spectrum None None
depending on
Tract[26] antibiotics
clinical status

Oral or
World Covering both
intravenous,
Gastroenterology 2007 Yes None Gram negative None None
depending on
Organization[27] and anaerobes
clinical status

Oral or
Broad
No, not intravenous,
SWAB[28] 2009 None spectrum None None
primarily depending on
antibiotics
clinical status