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CABI: Clinical management of Complicated intra-ABdominal Infection in United Kingdom hospitals
Version 3 Date 01.08.2016
Protocol
CABI: Clinical management of Complicated intra-ABdominal Infection
in United Kingdom hospitals
Principal Investigators: Mr Dermot Burke (Surgery), Dr Rachel Hyland
(Radiology), Dr Andrew Kirby (Microbiology), Dr Anne Melhuish (Infectious
Diseases), Dr Shafaque Shaikh (Surgery)
Version Number: 3
01.08.2016
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CABI: Clinical management of Complicated intra-ABdominal Infection in United Kingdom hospitals
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TABLE OF CONTENTS
PAGE
TABLE OF CONTENTS .............................................................................................................. II
PROTOCOL SUMMARY ............................................................................................................ III
1.1
Background Information .......................................................................................... 1
1.2
Rationale ................................................................................................................ 1
1.3
Study Objectives ..................................................................................................... 2
1.4
Study Outcome Measures ...................................................................................... 2
1.5
Study design ........................................................................................................... 3
1.6
Subject Inclusion Criteria ........................................................................................ 3
1.7
Subject Exclusion Criteria ....................................................................................... 3
1.8
Strategies for Recruitment and Retention ............................................................... 6
1.9
Study Procedures/Evaluations/ Questionnaire ........................................................ 6
1.10 Sample Size Considerations ................................................................................... 6
1.11 Final Analysis Plan ................................................................................................. 6
1.12 Publication/data sharing policy ................................................................................ 7
1.13 References ............................................................................................................. 7
APPENDICES ............................................................................................................................. 8
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CABI: Clinical management of Complicated intra-ABdominal Infection in United Kingdom hospitals
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PROTOCOL SUMMARY
Title:
CABI: Clinical management of Complicated intra-ABdominal
Infection in United Kingdom hospitals
Précis:
A multicentre audit and service evaluation of complicated
intra-abdominal infections (CABIs) in the United Kingdom to
assess current practice against national guidelines for the
management of CABI and to describe the surgical and
antibiotic management and outcomes of CABI. Data can be
collected from August 2016-May 2017.
Objectives:
Primary: To define compliance with guidance for the
management of CABI (audit).
Secondary: To describe clinical features and outcomes of
CABI in order to determine the efficacy of standard surgical
and antibiotic management of CABIs (service evaluation).
Population:
Patients will be included according to the following criteria:
Adult patients (> 18 years) with confirmed CABI between
August 2016 and February 2017. Patients will be excluded if
they had a CABI diagnosed within the previous year, if
antibiotics for their CABI was started >7 days prior to
screening and if they do not live in the area served by the
relevant hospital, given the requirement for follow up data. No
formal sample size calculation was performed.
Number of Sites:
As many UK sites as possible will be involved in this project.
Study Duration:
4-9 months (1-6 months recruitment, 3 months follow up)
Study
investigators
CABIs are managed by infectious disease doctors,
microbiologists, radiologists and surgeons. The data collected
on the management of these infections reflects this shared
management. Agreeing the involvement of a named staff
member from all specialties is likely to help all data fields be
completed.
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CABI: Clinical management of Complicated intra-ABdominal Infection in United Kingdom hospitals
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Schematic of Study Dates:
April to August 2016
Study site invited to participate via
 HQIP
 National Infection Trainee
Collaborative
 National Surgical Trainee
Collaborative
April to August 2016
Study site identifies investigators
April to August 2016
Pilot
August 2016 to May 2017
Data collection
May 2017 to June 2017
Data submitted
July 2017 to August 2017
Data analysis
September to October 2017
Investigators analyse manuscript
derived from submitted data
November 2017
The collaborative submit agreed
manuscript
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1.1
Background Information
Complicated intra-abdominal infection (CABI) is defined as an infection within the
abdomen where there is perforation of a viscus or a collection which is believed to be
infected. CABI is associated with increased morbidity and mortality (Solomkin 2010).
CABI occurs across a range of clinical specialties including colorectal surgery,
hepatobiliary surgery and gynaecological surgery.
A recent RCT was undertaken to compare 4 days vs approximately 8 days antibiotic
treatment for the antibiotic management of CABI after a source control procedure. No
significant difference in outcomes was identified, but there was a high rate of
complications (approx. 20%) in both treatment groups (Sawyer 2015).
A recent case note review (35 patients) of organ space surgical site infections after
colorectal surgery in Leeds suggested that the infections are heterogeneous, with
abscesses of variable size and number and that they are infrequently managed with
radiological drainage of the abscess (17%). Organ space SSIs were found to have a
high rate of relapse (40%) (Rothwell 2016, unpublished).
Guidelines for the management of CABI do not provide comprehensive evidence based
recommendations with which to guide management of most CABIs. Guidelines do
however provide expert opinion based recommendations on some aspects of the
management of CABI for use as audit standards (Solomkin 2010).
We intend to undertake a clinical trial of short course (≤ 10 days) vs long course (28
days) of antibiotics for the treatment of CABI. In order to design this trial it is necessary
to describe the patient population who suffer CABI, define the current management
strategies for CABI and determine outcomes associated with these management
strategies.
1.2
Rationale
The optimal strategy for the management of CABIs is uncertain due to a lack of clinical
evidence. In order to obtain such evidence clinical epidemiological data are required to
define the characteristics of CABIs in the United Kingdom NHS setting. These data will
inform the design of a study into CABI e.g. outcome rates to inform sample size
calculations. To obtain such data an audit of practice related to the management of
CABI will be carried out in combination with a service evaluation into the management
of CABI.
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1.3
Study Objectives
1- To describe the demographic and clinical characteristics of patients with CABIs
2- To describe practice variation in the management of CABI
3- To obtain outcome rates in patients with CABI
4- To associate management strategies with outcomes
5- To assess compliance with audit standards derived from the Infectious Disease
society of America guidelines for the diagnosis and management of CABI.
CABI definition: The diagnosis of CABI will be assigned with:

Intra-operative confirmation of an abscess, or

A combination of radiological AND clinical features consistent with CABI
including a fluid collection and/or perforated viscus, a temperature of ≥38 or less
than 35 degrees and a neutrophilia (neutrophil count > 7.5 x 10*9/L).
Fever (or hypothermia) and raised neutrophil count may not be present at the actual
time of recruitment: collaborators should note they may have preceded the date of
screening.
Day 0: The first day of infection will be defined as the first day antibiotic therapy was
initiated for the treatment of CABI. This date may precede or follow the day CABI
was suspected radiologically.
1.4
Study Outcome Measures
1. Relapse of CABI within 90 days of diagnosis
2. Time till relapse of CABI
3. Number of days hospitalization within 90 days of diagnosis
4. Death (all cause and attributable) within 90 days of diagnosis
5. Compliance with audit standards, see Appendix.
Relapse of a CABI definition: The diagnosis of a definite CABI relapse will be
assigned with:

Intra-operative confirmation of an abscess, or
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
A combination of radiological AND clinical features consistent with CABI
including a fluid collection and/or perforated viscus, a temperature of ≥38 or less
than 35 degrees and a neutrophilia (neutrophil count > 7.5 x 10*9/L).
Fever (or hypothermia) and raised neutrophil count may not be present at the actual
time of recruitment: collaborators should note they may have preceded the date of
screening.
In the absence of radiological imaging, but where no other source of infection was
identified, and the patient was managed for a relapsed CABI, a diagnosis of probable
CABI will be assigned.
A relapse can only occur after source control and/or antibiotic therapy to manage the
primary CABI has been considered to be successful. This will normally be demonstrated
by antibiotics having been stopped and there being no further source control procedures
planned.
1.5
Study design
Design: Observational multicentre cohort study.
The study population are hospitalized adults within NHS hospitals with CABI.
Timeline
1.6

Start data: August 2016, Completion of enrolment: February 2017

End of data collection: May 2017

Duration of follow up: 90 days post CABI diagnosis

Data collection methods: Medical case note review
Subject Inclusion Criteria
Patients may be included according to the following criteria: adult patients (> 18 years)
with CABI between August 2016 and February 2017.
1.7
Subject Exclusion Criteria
Patients are excluded if they had a CABI diagnosed within the previous year, if antibiotic
treatment for their CABI was started >7 days prior to screening and if they do not live in
the area served by the relevant hospital given the requirement for follow up data.
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The conditions excluded are intended to ensure we are studying primary episodes of
CABI for which there is evidence there may be a high risk of relapse, that the cases
included are not biased towards more complicated cases, and to exclude primary
appendicitis managed surgically for which good data already exist. In the case of
necrotising pancreatitis, SPB and CAPD peritonitis these pathologies are excluded as
they consist of a discrete disease process. Conditions for inclusion and exclusion are
summarised in Table 1. These lists are for guidance and are not exhaustive; clarification
can be sought on other conditions not listed.
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Table 1: Clarification of which infections are to be included and excluded from CABI
Included conditions
Excluded conditions
Post-operative surgery CABI including colorectal
(including appendiceal), biliary, small bowel and
gastric surgery (including iatrogenic perforations)
e.g. Peri-anastomotic abscess
Uncomplicated cholecystitis/cholangitis/gall
bladder empyema (no perforation or extrabiliary abscess)
Gastrointestinal fistula communicating with the
peritoneal space
Skin and soft tissue infection/abscess not
communicating with the peritoneal space
Oesophageal rupture into the peritoneal space
Spontaneous bacterial peritonitis &
continuous ambulatory peritoneal dialysis
& perforated duodenal/gastric ulcer
Ischaemic bowel and volvulus with perforation
Primary complicated or uncomplicated
appendicitis managed surgically.
Perforations associated with malignancies
Intraabdominal infection associated with
pancreatitis
Complicated diverticulitis & perforated Meckel’s
diverticulum
Adenexal abscess without communication
with the peritoneal cavity
Clostridium difficile colitis with perforation
Pelvic inflammatory disease
CABI secondary to inflammatory bowel disease
pathology
Primary complicated appendicitis managed
conservatively
Renal/Adrenal/Liver/Spleen abscess communicating
with the peritoneal cavity.
Adenexal abscess communicating with the peritoneal
cavity
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1.8
Strategies for Recruitment and Retention
Patients will not be formally recruited.
Information governance approval will be requested at each site to complete this study
as an audit and service evaluation. Information governance approval has been provided
for the lead site-Leeds Teaching Hospitals NHS Trust.
Each investigator will submit a minimum of 7 patients to the study.
To reduce bias only patients with a new diagnosis of CABI will be included.
Investigators will also be asked to, where possible, recruit consecutively identified
patients who meet the inclusion criteria. No formal screening protocol is recommended.
Possible screening processes could involve:

Identification of consecutive patients on ward round

Screening of a cohort of patients on a defined day or week, or at a particular time
each day

Reviewing patients having undergone radiological imaging

Reviewing radiological reports on electronic results servers
Screening should try and avoid biasing to more complicated patients e.g. only including
those who were identified during out of hours work and so may be biased to more
unwell patients.
1.9
Study Procedures/Evaluations/ Questionnaire
Data will be collected on case report forms, see Appendix S1 for the required dataset.
1.10
Sample Size Considerations
Each investigator will be required to submit a minimum 7 patients’ data to the national
data set. Where possible it is anticipated this recruitment target will be exceeded.
1.11
Final Analysis Plan
Data will be requested within two months of the end of study date. Data analysis will be
completed over the subsequent four months. Results are reported in accordance with
the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)
statement for observational studies (von Elm 2007). Data will be analysed with
reference to compliance with audit standards. Data will be analysed as proportions.
Management strategies will be compared to outcomes, with tests for significant
differences in outcomes analysed according to stratified management strategies.
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1.12
Publication/data sharing policy
All investigators submitting data on seven patients will be eligible to review the
manuscript written by the principal investigators (Burke, Hyland, Kirby, Melhuish,
Shaikh) and therefore contribute academically. This academic contribution will be
recognised with authorship on submitted manuscripts.
1.13
References
Solomkin JS, Mazuski JE, Bradley JS, Rodvold KA, Goldstein EJ, Baron EJ, et al.
Diagnosis and management of complicated intra-abdominal infection in adults and
children: guidelines by the Surgical Infection Society and the Infectious Diseases
Society of America. Clin Infect Dis. 2010;50(2):133-64.
Rothwell A, Burke D, Burnside G, Kirby A. Characteristics of Organ Space Surgical Site
Infection after colorectal surgery. Unpublished
von Elm E, Altman DG, Egger M, Pocock SJ, Gotzsche PC, Vandenbroucke JP. The
Strengthening the Reporting of Observational Studies in Epidemiology (STROBE)
statement: guidelines for reporting observational studies. Lancet 2007; 370: 1453–1457.
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APPENDICES
Demographics and Baseline Data
Local Patient ID:
Study ID:
Gender:
Initial admission date:
Age range
18-29
30-39
40-49
50-59
60-69
70-79
80-89
90-99
≥100
Site (origin) of CABI (please circle any that apply)
Appendix
Psoas muscle
Biliary
Reproductive tract
Colon
Small bowel
Kidney/Adrenal
Spleen
Liver
Unknown
Peptic Ulcer
Other (please state)
Underlying pathology (please circle any that apply)
Adnexal abscess
Immunosuppression
Anatomical abnormality
Ischaemic bowel
Appendicitis
Pancreatitis
Biliary stones
Pelvic inflammatory disease
Cancer
Perforated peptic ulcer
Chemo-radiotherapy in last 12 months
Perforated abdominal viscus at onset of CABI
Clostridium difficile colitis
Post-operative complication (< 6 months)
Crohn’s disease
Ulcerative colitis
Diverticular disease
Spontaneous
Drug reaction
Volvulus
Fistula
Colo-cutaneous
Colo-vaginal
Colo-urinary
Colo-intra-abdominal
Unknown
Other (please state)
Other
Iatrogenic perforated bowel
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Primary Management of CABI
Source control procedure as part of primary CABI
management plan? (please circle)
Radiological (CT guided) percutaneous drainage
Radiological (U/S guided) percutaneous drainage
Surgical: Resection and anastomosis or closure
Surgical: drainage only
Surgical: Resection and proximal diversion
Surgical: Closure of perforation only with/without
washout/drain
Surgical: Drainage and diversion
None
Not radiologically drainable
If no source control procedure, please select from
the reasons opposite: (please circle)
Not surgically drainable
Clinical decision to manage with antibiotics
Patient clinically responded to antibiotic therapy
Patient refused drainage
Patient too unwell for radiological drainage
Patient too unwell for surgical drainage
Unknown
Anticoagulated
Other (please give details)
If multiple collections are present, and the patient
underwent drainage, were all collections drained?
Were cultures sent at the time of the CABI being
diagnosed (blood cultures +/-samples from the site
of infection)?
Co-amoxiclav (+/metronidazole)
Yes
No
Unknown
Yes
No
Unknown
Piperacillin-tazobactam
(+/- aminoglycoside)
Cefuroxime and
metronidazole
Primary IV antibiotic6/7
regimen
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Carbapenem
Tigecycline
Quinolone and
metronidazole (+/- beta
lactam +/- glycopeptide)
Antifungal
Glycopeptide, Aminglycoside
and metronidazole
Aminoglycoside and
metronidazole (+/- betalactam)
Glycopeptide, beta-lactam
and metronidazole
Temocillin, metronidazole and
glycopepetide or beta-lactam
Unknown/Missing
Other (please state):
None
Duration of IV treatment8 (days)?
Primary oral antibiotic
regimen6/7
Oral cephalosporin
and metronidazole
Co-amoxiclav
Quinolone and
metronidazole (+/- beta
lactam)
Unknown/Missing
Antifungal
Other (please state):
None
Duration of oral treatment8 (days)?
Change of primary antibiotic treatment for initial
CABI due to antibiotic resistance?
Yes
No
Unknown
Change of primary antibiotic treatment for initial
CABI due to failure of antibiotic therapy?
Yes
No
Unknown
Was an additional or unplanned source control
procedure required as a result of failure of the
primary CABI management plan?
Yes
No
Unknown
What date was the additional or unplanned source
control procedure? (if multiple give earliest date
only)
Outcomes
Date of CABI diagnosis
Relapse within 90 days3
Yes-Definite
If yes, date of relapse and date of CABI diagnosis?
Date of relapse
Failure of antibiotic
treatment
Aetiology of relapses (circle all that apply)
Death (within 90 days)?
Yes
If yes, date of death
Number of days hospitali
Date of death:
Yes-Probable
No
Failure of source control
Unknown/Other
No
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Number of days hospitalisation (within the 90 days
after CABI diagnosis)?
Date improved:
Date patient has clinically improved from initial
CABI: Apyrexial (<38) for > 24 hours and WCC <11?
Or discharged before Apyrexial (<38) for > 24 hours
and WCC <11?
Primary Imaging characteristics5
(Please discuss with a radiologist when answering the questions)
Date of imaging
Modality of imaging used to make
the diagnosis
Does imaging demonstrate a
collection or free fluid?
Single
Multiple
<5
>5
Maximum depth2 of biggest
collection (cm)
Anastomosis
Yes
No
Unknown
Evidence of
Yes
fistulation
No
Not stated
Radiological
Yes
drainage
feasible in
No
radiologist’s
opinion?
CT
US
Collection(s)
Free fluid
Neither
Collection(s)
Free fluid
Neither
Collection
Evidence of
leak
Yes
No
Unknown
If Yes, location of fistula?
If yes, would radiological
drainage be advised?
Yes
No: Surgical intervention
preferred
No: Collection too small
No: Please state reason
Microbiological characteristics of samples relevant4 to CABI as judged by clinician
(Please liaise with a microbiologist to obtain this information)
Staphylococcus aureus
MRSA
Enterococcus
Vancomycin resistant Enterococcus
Coliform (Enterobacteriaceae)
Augmentin resistant coliform
Yes
Yes
Yes
Yes
Yes
Yes
No
No
No
No
No
No
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Piperacillin-tazobactam resistant coliform
AmpC/ESBL resistant coliform
Carbapenemase producing coliform (CPE)
Ciprofloxacin resistant coliforms
Anaerobes
Yeasts
Able to collect this information?
Yes
Yes
Yes
Yes
Yes
Yes
Able
No
No
No
No
No
No
Unable
Case report form advice
1- Where an event has not been identified after reviewing notes, please report this
as having not occurred i.e. answer no to the question.
2- Depth of collection does not relate to the location of the collection in relation to
the skin.
3- Relapse of a CABI definition: The diagnosis of a CABI relapse will be assigned
as definite with: A combination of radiological AND clinical features consistent
with CABI or Intra-operative confirmation of an abscess or perforated abdominal
viscus, or Pathogenic bacteria from a sterile intra-abdominal site in combination
with clinical or radiological features or In the absence of radiological imaging, but
where no other source of infection was identified, and the patient was managed
for a relapsed CABI, a diagnosis of probable CABI was assigned. A relapse can
only occur after surgical and antibiotic therapy to manage the primary CABI has
been considered to be successful. This will normally be demonstrated by
antibiotics having been stopped and there being no further source control
procedures being planned.
4- Relevant clinical samples include blood cultures, surgical samples, intraabdominal drain samples and surgical wound samples (excluding skin bacteria
such as coagulase negative staphylococcus, Diptheroids, Corynebacteria)
5- Where multiple radiological tests have been performed please report only the
imaging completed closest to the time of CABI diagnosis
6- Antibiotics and antibiotic class: Aminoglycosides includes: Amikacin and
Gentamicin, Beta-lactams includes all penicillins (e.g. amoxicillin),
cephalosporins, carbapenems and aztreonam. Carbapenems includes:
Ertapenem, Imipenem and Meropenem. Glycopeptides includes: Teicoplanin and
Vancomycin. Quinolones includes: Ciprofloxacin and levofloxacin
7- The primary antibiotic is the predominant (jn terms of number of days) antibiotic
administered)
8- Duration of treatment includes all IV/oral antibiotics administered from the start of
treatment until antibiotics were stopped.
Audit standards
1- A CT scan is the preferred radiological imaging modality to investigate for CABI.
2- A source control procedure should be attempted in the management of CABI
3- Microbiological cultures should be sent at the time of the CABI being diagnosed
(blood cultures +/-samples from the site of infection).
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4- If resistant bacteria were identified at the time of initial intervention and there are
persistent signs of infection, pathogen-directed therapy is recommended.
5- Antimicrobial therapy of established infection should be limited to 4–7 days,
unless it is difficult to achieve adequate source control.
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