EXTENDed Antibiotic Durations Compared to Standard Durations for Patients With Complicated Intra-abdominal Infection.

Inclusion Criteria:

• Adults (≥ 16 years) with cIAI* (see cIAI definition)

• Being treated with antibiotics until the point of randomisation, but within 10 daysof initiation of effective antibiotic treatment** for cIAI

• Ability to provide informed consent by the patient or their consultee.

• More than 72 hours*** of active in-patient management for the patients cIAI isrequired

• In the event that the patient is re-admitted to hospital during the trial period,they are likely to be admitted to a hospital participating in the EXTEND trial.

Patients will be included in the trial whether or not they undergo surgical or radiological source control procedures.

• cIAI is defined by the following case definition:

• A clinical presentation consistent with cIAI, plus

• Fever (temperature of ≥ 37.8°C) and/or a neutrophilia (> 7.5×109/L) and/orneutropaenia (<1.8 x 109 /L) and/or intestinal pathogens cultured from sterile sites (closed peritoneum or blood) around the time of cIAI diagnosis, plus

• Evidence of pathologic findings on radiologic examination, or

• Evidence of pathologic findings at operation

** The first day of effective antibiotic treatment will be determined by thepatient's clinical team or clinical research team. Antibiotics that do not counttowards these 10 days of effective treatment are:

• Antibiotic prophylaxis e.g., penicillin for splenectomy, elective surgery antibioticprophylaxis, UTI prophylaxis

• Treatment for other infections that is not effective for cIAI e.g., cystitis.Antibiotics that re often used for cystitis and aren't effective for cIAI includeCephalexin, Fosfomycin Trimethoprim, Nitrofurantoin, and Pivmecillinam.

• Oral antibiotics prescribed to treat infection prior to hospitalisation

• Previous courses of treatment antibiotics: A previous course is one stopped for 48hours or more

• The further 72 hours starts from the first day of effective antibiotictreatment i.e., for a patient admitted to hospital with a cIAI, 3 days ofadmission are needed. Where a patient is already in hospital e.g., a postoperative patient, a further 3 days of admission are required starting from thepoint of the first day of effective antibiotic treatment.

Exclusion Criteria:

• Perforated gastric ulcer or duodenal ulcer treated within 24 hours of the onset ofsymptoms.

• Traumatic injury to the bowel (including iatrogenic or intra-operative) treatedwithin 12 hours of injury.

• Uncomplicated diverticulitis defined as an episode with a short history and withclinical signs of diverticulitis, with an increased body temperature andinflammatory parameters, verified by computed tomography (CT), and without any signof complications such as abscess, free air or fistula.

• Grade 1 to 3 appendicitis. To be eligible patient must have Grade 4 or 5appendicitis defined by the 2017 American Association for the Surgery Trauma GradingSystem with either generalised peritonitis at surgery, or no or partial sourcecontrol e.g. radiological drainage

• Non-perforated cholecystitis.

• Ischemic or necrotic intestine without perforation

• Uterine perforation following uterine surgery treated <six hours following injury.

• cIAIs with a low risk of complications who may receive more than 72 hoursantibiotics are not intended to be included, such as those listed above. Traumaticinjury to the bowel (including iatrogenic or intra-operative) treated within 12hours of injury, Uterine perforation following uterine surgery treated within sixhours of injury, Perforated gastric ulcer or duodenal ulcer treated within 24 hoursof the onset of symptoms). Clinician assessment on the eligibility of patientsreceiving more than 72 hours of in-patient surgical care and antibiotics for theircIAI may be required in patients who have clinically improved at this point and donot require active surgical care but remain in hospital and on antibiotics.

• Current enrolment in another trial dictating antibiotic treatment duration.

• Previous Clostridium difficile infection

• Infected necrotic pancreatitis

• Concomitant infection requiring ≥4 weeks antibiotic therapy including Intra-hepaticabscess/es planned to be treated with fixed-extended-duration antibiotics of 4 to 6weeks antibiotics, osteomyelitis, and endocarditis.

• Peritoneal dialysis

• Previously recruited for the EXTEND trial

• Treatment with Interleukin-6 Inhibitors

• High likelihood of death within 72 hours of cIAI randomisation in the opinion of thelocal Investigator

• Limitations in treatment decided before inclusion. Limitations in treatment thatexclude patients from the EXTEND trial are those clinical decisions linked to anexpectation the patient will die during this episode of infection.

• Patient with persistent cIAI of more than 6 months duration

A maximum of 20% of participants entering the trial can have a source of cIAI as the appendix. If 230 patients with appendix as the source are recruited, this will become an exclusion criteria for subsequent patients.

Note: There are absolute exclusions that preclude trial participation. These include: C. difficile infection, Infected necrotic pancreatitis, Concomitant infection requiring ≥4 weeks antibiotic therapy, Treatment with Interleukin-6 Inhibitors, High likelihood of death within 72 hours of randomisation, Limitations in treatment decided before inclusion, Peritoneal dialysis, Previously recruited for the EXTEND trial, Patient with persistent cIAI of more than 6 months duration and a patient with persistent cIAI of more than 6 months duration. If a patient has two intraabdominal infections, the presence of one of the following ineligible infections does not make a patient ineligible if the other cIAI is eligible: Perforated gastric ulcer or duodenal ulcer treated within 24 hours of the onset of symptoms, Traumatic injury to the bowel (including iatrogenic or intra-operative) treated within 12 hours of injury, Uncomplicated diverticulitis, Ineligible cases of appendicitis (see exclusion criteria above), Uncomplicated cholecystitis, Ischemic or necrotic intestine without perforation, Uterine perforation following uterine surgery treated within six hours of injury or cIAI with a low risk of complications.