Figure S1. Methodological quality assessment of the risk of bias for each included study. (a) Risk of bias

summary; (b) risk of bias graph.

Figure S2. Sensitivity analysis from both the bayesian network meta-analysis (open circle; CrI, credible

intervals) and traditional meta-analysis (solid circle; CI, credible interval) for clinical treatment success by

low risk of selection bias for concealment. Abbreviations: BAPM, biapenem; DOPM, doripenem; IC,

imipenem/cilastatin; ICRB, imipenem/cilastatin/relebactam; MEPM, meropenem; TGC, tigecycline.

Figure S3. Sensitivity analysis from both the bayesian network meta-analysis (open circle; CrI, credible

intervals) and traditional meta-analysis (solid circle; CI, credible interval) for clinical treatment success by

excluding studies with small sample size. Abbreviations: BAPM, biapenem; DOPM, doripenem; IC,

imipenem/cilastatin; ICRB, imipenem/cilastatin/relebactam; MEPM, meropenem; TGC, tigecycline.

Figure S4. Sensitivity analysis from both the bayesian network meta-analysis (open circle; CrI, credible

intervals) and traditional meta-analysis (solid circle; CI, credible interval) for microbiological treatment

success by low risk of selection bias for concealment. Abbreviations: BAPM, biapenem; DOPM, doripenem;

IC, imipenem/cilastatin; ICRB, imipenem/cilastatin/relebactam; MEPM, meropenem; TGC, tigecycline.

Figure S5. Sensitivity analysis from both the bayesian network meta-analysis (open circle; CrI, credible

intervals) and traditional meta-analysis (solid circle; CI, credible interval) for microbiological treatment

success by excluding studies with small sample size. Abbreviations: BAPM, biapenem; DOPM, doripenem;

IC, imipenem/cilastatin; ICRB, imipenem/cilastatin/relebactam; MEPM, meropenem; TGC, tigecycline.

Figure S6. Forest plot from both the bayesian network meta-analysis (open circle; CrI, credible intervals)

and traditional meta-analysis (solid circle; CI, credible interval) for adverse events. Abbreviations: BAPM,

biapenem; DOPM, doripenem; IC, imipenem/cilastatin; ICRB, imipenem/cilastatin/relebactam; MEPM,

meropenem; TGC, tigecycline.

Figure S7. SUCRA and rank probability for adverse events. (A) SUCRA for adverse events; (B) rank

probability for adverse events. Abbreviations: BAPM, biapenem; DOPM, doripenem; IC,

imipenem/cilastatin; ICRB, imipenem/cilastatin/relebactam; MEPM, meropenem; TGC, tigecycline.

Figure S8. Forest plot from both the bayesian network meta-analysis (open circle; CrI, credible intervals)

and traditional meta-analysis (solid circle; CI, credible interval) for mortality. Abbreviations: BAPM,

biapenem; DOPM, doripenem; IC, imipenem/cilastatin; ICRB, imipenem/cilastatin/relebactam; MEPM,

meropenem; TGC, tigecycline.

Figure S9. SUCRA and rank probability for mortality. (A) SUCRA for mortality; (B) rank probability for

adverse events. Abbreviations: BAPM, biapenem; DOPM, doripenem; IC, imipenem/cilastatin; ICRB,

imipenem/cilastatin/relebactam; MEPM, meropenem; TGC, tigecycline.

Table S1 The definitions of clinical and microbiological and timing of evaluation.

Author/Year definition of Complicated intra-abdominal infections clinical evaluability microbiological outcome

Babinchak 2005

Complicated intra-abdominal infections included such conditions intra-abdominal abscess (including liver and spleen) that developed in a patient following surgery after receiving standard antibacterial therapy (i.e., antibiotics for at least 48 h but not more than 5 days); appendicitis complicated by perforation and/or a periappendiceal abscess; perforated diverticulitis complicated by abscess formation or fecal contamination; complicated cholecystitis with evidence of perforation, empyema, or gangrene; perforation of a gastric or duodenal ulcer with symptoms exceeding 24 h in duration; purulent peritonitis or peritonitis associated with fecal contamination; or perforation of the large or small intestine with abscess or fecal contamination.

Cure: the course of study drug and the initial intervention (operative and/or radiologically guided drainage procedure) resolved the intra-abdominal infectious process.

Microbiological response by patient was categorized at the test of cure visit as eradication, persistence, or superinfection (i.e., the emergence of a new isolate was documented at the site of infection with worsening signs and symptoms of infection).

Basoli 1997

Serious (requiring hospitalization), complicated (requiring surgical intervention within 24 h of diagnosis/enrolment in the study), and mild to moderate in severity (not life-threatening) intra-abdominal infections.

Cure: no signs or symptoms of infection and no further antimicrobial therapy; failure: indicating no improvement, infection progression or death due to infection; or late failure indicating recurrence between cessation of antibiotics and follow-up.

Microbiological response by patient was categorized at the end and at least 7-10 days after discontinuation of the study-drug therapy, was categorized in evaluable patients as eradicated, relapsed, persistent or persisted acquiring resistance.

Brismar 1995

Patients suspected intra-abdominal infections were entered into the trial. The infection was confirmed at laparotomy or by aspiration of an abscess before treatment was started.

Cure:complete remission of local and systemic signs and symptoms of infection without further surgical intervention, addition of other antibiotics and without recurrence of symptoms; (ii) failure: no improvement or deterioration of signs and symptoms; (iii) relapse: initial response by the end of therapy followed by local or general signs of recurrent infection at follow-up.

At least one organism sensitive to the test drugs should be isolated from the site of infection before the start of treatment.

Brismar 1996

A 'complicated infection' was defined according to the General Guidelines for the Evaluation of New Anti-Infective Drugs for the Treatment of Intraabdominal and Pelvic Infections. i.e. an operative procedure or percutaneous drainage is required for diagnosis and management; and the duration of antibiotic therapy must be at least 5 days. The infection was confirmed at laparotomy or by aspiration of an abscess before treatment was started.

Cure: the patient completed therapy and showed recovery from the acute infection; failure: the patient had no response during antibiotic therapy or initial recovery from infection followed by deterioration at early or late follow-up requiring further ntibacterial therapy, or death from the infection; or indeterminate all other situations.

Eradication (documented or presumed): the pathogen was not present in the culture taken, or favorable clinical response precluded availability of specimen for culture; persistance (documented or presumed): the pathogen was present in the culture taken or the culture data were not available in a patient with a clinical failure; or indeterminate: culture data were not available for the pathogen in a patient with an indeterminate clinical outcome.

Cannavino 2015 Patients with complicated intra-abdominal infection. NA NA

Chen 2010Undergone a laparotomy, laparoscopy, or percutaneous drainage of an intraabdominal abscess and had a known or suspected diagnosis of cIAI.

The clinical response to study drug was determined by the investigator at the test-of-cure visit and categorized as cure, failure, or indeterminate.

Microbiologic response by patient was categorized at the test of cure visit as eradication, persistence, superinfection (i.e., the emergence of a new isolate was documented at the site of infection with worsening signs and symptoms of infection), or indeterminate.

Chen 2018 Laparotomy, laparoscopy, or percutaneous drainage of an intra-abdominal abscess within 24 hours of enrollment; for subjects enrolled preoperatively, study drugs were given with strong suspicion or confirmed diagnosis of IAI with baseline intra-abdominal culture taken from theinfected site; cIAI duration ,2 weeks; confirmation of minimal clinical criteria when IAI was diagnosed or highly suspected; and agreement to use a highly effective contraceptive for females of childbearing potential.

The study drug (ie, tigecycline or imipenem/cilastatin) and the initial intervention (operative and/or radiologically controlled drainage procedure) resolved the intra-abdominal infection. The relevant clinical signs and symptoms of infection at baseline disappeared or recovered to normal, and relevant non-microbiological results of

The baseline pathogen was absent in repeat cultures obtained from the original site of the intra-abdominal infection through the TOC assessment; or a clinical response of cure precluded the necessity of a repeat intra-abdominal culture.

laboratory tests returned to normal level (radiological test was at the discretion of investigators) or the resolution of signs and symptoms so that no further therapy was required.

Fomin 2005A laparotomy, laparoscopy, or percutaneous drainage of an intra-abdominal abscess and had a known or suspected diagnosis of complicated intra-abdominal infections.

Cure: the course of study drug and the initial intervention (operative and/or radiologically guided drainage procedure) resolved the intraabdominal infectious process.

Microbiologic response by patient was categorized as eradication, persistence, superinfection (i.e., the emergence of a new isolate was documented at the site of infection or at a distant site with worsening signs and symptoms of infection), and indeterminate.

Fomin 2008

Complicated intra-abdominal infections included: intra-abdominal abscess (including liver and spleen) that developed in a patient following surgery after receiving standard antibacterial therapy (i.e., antibiotics for at least 48 hours but not more than 5 days); appendicitis complicated by perforation and/or a periappendiceal abscess; perforated diverticulitis complicated by abscess formation or fecal contamination; complicated cholecystitis with evidence of perforation, empyema; perforation of a gastric or duodenal ulcer with symptoms exceeding 24 hours in duration; purulent peritonitis or peritonitis associated with fecal contamination; or perforation of the large or small intestine with abscess or fecal contamination.

Cure: the course of study drug and the initial intervention (operative and/or radiologically guided drainage procedure) resolved the intra-abdominal infectious process.

Microbiological response by patient was categorized at the test-of- cure visit as eradication (documented or presumed), persistence(documented or presumed), or superinfection (i.e., the emergence of a new isolate was documented at the site of infection with worsening signs and symptoms)

Geroulanos 1995

intra-abdominal infections with evidence of a systemic inflammatory response (such as pyrexia, elevated white cell count, hypotension, increased heart and respiratory rates, altered mental status) and physical signs consistent with abdominal infection (which included abdominal tenderness, presence of localised or diffuse abdominal wall rigidity, abdominal mass, or ileus).

Cured: complete resolution of local and systemic signs and symptoms of infection at the end of the treatment period without the addition of other antibiotics or recurrence of symptoms; improved: significant improvement in local symptoms and systemic signs without complete resolution of infection but allowing study treatment to be stopped

Success: all causative pathogens eradicated; presumed success: no further culture available due to clinical improvement; partial success: one or more, but not all of the organisms of a polymicrobial infection eradicated, associated with clinical improvement or cure;

Kanellakopoulou 1993

The patients were suffering from diffuse or local peritonitis of moderate severity complicating in most cases gangrenous appendicitis, stomach perforation or gallbladder disease.

The response to therapy was classified as cure, improvement or failure.

All infections had to be confirmed subsequently by surgical findings and positive bacterial cultures of peritoneal fluid.

Lucasti 2008

cIAI diagnoses included cholecystitis with rupture, perforation, or progression of the infection beyond the gallbladder wall; diverticular disease with perforation or abscess; appendiceal perforation or periappendiceal abscess; acute gastric and duodenal perforations (only if operated on at >24 hours after the perforation had

Clinical cure was defined as the complete resolution or significant improvement of signs or symptoms of the index infection.

Eradication and persistence were used to indicate the absence or presence, respectively, of a causative pathogen from an appropriately obtained specimen at the site of infection.

occurred [in patients operated on at <24 hours, a full course of antibiotic treatment is not necessary1]); traumatic intestinal perforation (only if operated on at >12 hours); peritonitis due to perforated viscus, occurring postoperatively or due to other focus of infection; and/or intra-abdominal abscess, including in the liver or spleen.

Lucasti 2016

Eligible diagnoses included the following: cholecystitis (including gangrenous) with rupture, perforation, or progression of infection beyond the gallbladder wall; diverticular abscess; appendiceal perforation and periappendiceal abscess; acute gastric and duodenal perforations, if operated on 24 h after occurrence; traumatic perforation of the intestines, if operated on 12 h after occurrence; peritonitis due to perforated viscus, surgical intervention, or other focus of infection (but not spontaneous bacterial peritonitis associated with cirrhosis and chronic ascites);and intra-abdominal abscess.

Favorable clinical response (cure or sustained cure) was defined as resolution of all or most presenting signs and symptoms of IAI infection without the need for additional antibiotic therapy.

Microbiologic response was imputed from the clinical response if follow-up cultures from the site of infection were not available.

Oliva 2005

Complicated intra-abdominal infections included conditions such as an intra-abdominal abscess (including liver and spleen) that developed in a postsurgical patient after receiving standard antibacterial therapy (ie, at least 48 hours, but note more than 5 days of antibiotics); appendicitis complicated by perforation and/or a periappendiceal abscess; perforated diverticulitis complicated by abscess formation or fecal contamination; complicated cholecystitis with evidence of perforation, empyema, or gangrene; perforation of a gastric or duodenal ulcer with symptoms exceeding 24 hours; purulent peritonitis or peritonitis associated with fecal contamination; or perforation of the large or small intestine with abscess or fecal contamination.

Cure: the course of study drug and the initial intervention (operative and/or radiologically guided drainage procedure) resolved the intra-abdominal infectious process

Microbiologic response by patient was categorized at the test-of-cure visit as eradication, persistence, superinfection (ie, the emergence of a new isolate was documented at the site of infection with worsening signs and symptoms of infection).

Zanetti 1999Hospitalised adults (≥18 years) with moderately severe IAIs defined by the presence of abdominal tenderness, guarding and rigidity were enrolled.

Cure: complete remission of local and systemic signs and symptoms of infection without the addition of other antibiotics and without recurrence of symptoms.

Eradication: satisfactory clinical response without microbiological sample.