Background
Methods
-
The 2010 Surgical Infection Society and Infectious Diseases Society of America consensus guidelines for the diagnosis and management of complicated intra-abdominal infection in adults and children [1].
-
The 2010 Canadian practice guidelines for surgical intra-abdominal infections [4].
-
The 2014 Asian Consensus Taskforce on Complicated Intra-abdominal Infections guidelines for antibiotic management of complicated intra-abdominal infections in adults [17].
-
The 2015 French Society of Anesthesia and Intensive Care guidelines for the management of intra-abdominal [18].
-
The 2017 Surgical Infection Society revised guidelines for the management of intra-abdominal infection [19].
-
The 2017 World Society of Emergency Surgery guidelines for the management of intra-abdominal infections [3].
-
The 2018 Tokyo guidelines for the antimicrobial therapy in acute cholangitis and cholecystitis [20].
-
The 2013 American College of Gastroenterology guidelines for the management of acute pancreatitis [21].
-
The 2013 International Association of Pancreatology/American Pancreatic Association working group guidelines for the management of acute pancreatitis [22].
-
The 2015 Japanese guidelines for the management of acute pancreatitis [23].
Level of Evidence
Grading category | Definition |
---|---|
1 | Based upon high-level evidence with multiple well-designed, controlled, randomized blinded studies and meta-analysis. There is uniform consensus that the intervention is adequate. |
2A | Based upon lower level of well-controlled, non- blinded or randomized studies, with retrospective reviews. There is uniform consensus that the intervention is adequate. |
2B | Based upon lower level of well-controlled, non- blinded or randomized studies, with retrospective reviews. There is majority consensus that the intervention is adequate. |
3A | Based upon any evidence that is less than well-controlled, or randomized, or large sample studies, mostly retrospective. There is uniform consensus that the intervention is adequate. |
3B | Based upon any evidence that is less than well-controlled, or randomized, or large sample studies, mostly retrospective. There is no uniform consensus that the intervention is adequate. |
3C | Based upon any evidence that is less than well-controlled, or randomized, or large sample studies, mostly retrospective. There is no consensus that the intervention is adequate. |
4A | There is any level of evidence from literature against the intervention. There is uniform consensus against the intervention. |
Results
Microbiological data: Antimicrobial susceptibility in Lebanon
Classification of cIAI
-
Biliary infections and non-biliary infections have the same causative bacterial organisms; however, the importance of yeast infections is less pronounced in biliary infections compared to non-biliary [20]. In addition, antimicrobial pharmacodynamics parameters differ markedly between the 2 anatomic locations. For example, tigecycline concentration is much higher in the biliary tree compared to the abdominal cavity [38].
-
The importance and implication of the bacterial pathogens in the etiology and progression of pancreatitis is different from that in biliary and non-biliary cIAI, and accordingly recommendations for therapy differ.
Definitions
-
cIAI extend beyond the organ that is the source of the infection, and cause either localized peritonitis, referred to as abdominal abscess, or diffuse peritonitis, depending on the ability of the host to contain the process within a part of the abdominal cavity [1‐3, 19]. Hence, cIAI include abdominal cavity infections, biliary infections and pancreatitis.
-
Peritonitis and intraperitoneal bacterial infections can be classified as primary, secondary or tertiary infections [1‐3, 19]:
-
Primary infections refer to spontaneous bacterial invasion of the peritoneal cavity. This mainly occurs in infancy and early childhood, in cirrhotic patients and immunocompromised hosts.
-
Secondary infections describe peritoneal infections secondary to intra-abdominal lesions, such as perforation of the hollow viscus, bowel necrosis, nonbacterial peritonitis, or penetrating infectious processes.
-
Tertiary infections are characterized by persistent or recurrent infections with organisms of low intrinsic virulence or with predisposition for the immunocompromised patient. It usually follows operative attempts to treat secondary peritonitis and is almost exclusively associated with a systemic inflammatory response.
-
-
CA-cIAI with risk of being caused by 3GC-resistant Enterobacteriaceae should be suspected in patients with [1‐3, 19, 30, 31]:
-
Known prior colonization or infection with 3GC-resistant Enterobacteriaceae
-
Exposure to antimicrobials within the previous 90 days
-
History of home infusion therapy (including antibiotics)
-
Home wound care
-
Family member with 3GC-resistant Enterobacteriaceae
-
Immunosuppressive disease and/or therapy
-
-
Hospital/Health care-associated cIAI (HA-cIAI) are defined as infections occurring in patients [1‐3, 19]:
-
Admitted to the hospital for 48 h or more before the onset of infection, in whom the cIAI had not started before admission
-
Hospitalized for 2 or more days within the preceding 90 days
-
Who are residents of nursing homes or extended care facilities
-
On chronic dialysis
-
-
Severity of illness reflects the risk of mortality in general.
-
Peritoneal/ intraperitoneal infections are stratified to different risk groups (mild to moderate and severe) based on predictable clinical parameters and comorbid conditions as measured by the APACHE II score. Patients with mild to moderate infections are those with an APACHE II score < 15 and those with severe infections have APACHE II score ≥ 15 [4].
-
Similar to peritoneal/intraperitoneal infections, cholangitis is stratified to mild to moderate and severe based on predictable clinical parameters and comorbid conditions as measured by the APACHE II score [4].
-
In cholecystitis, severity of illness is stratified according to the following grading system [20, 39]:
-
Mild (Grade 1): Acute cholecystitis that does not meet the criteria for a severe grade: mild gallbladder inflammation and no organ dysfunction.
-
Moderate (Grade 2): The presence of one or more of the following parameters:
-
Elevated white-cell count (> 18,000 cells/μL),
-
Palpable tender mass in the upper right abdominal quadrant,
-
Marked local inflammation including biliary peritonitis, pericholecystitic abscess, hepatic abscess, gangrenous cholecystitis, emphysematous cholecystitis,
-
Duration of signs and symptoms > 72 h.
-
-
Severe (Grade 3): The presence of one or more of the following parameters:
-
Cardiovascular dysfunction: hypotension requiring treatment with dopamine at a dose ≥5 mcg/kg/min or any dose of dobutamine,
-
Neurologic dysfunction: decreased level of consciousness,
-
Respiratory dysfunction: ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen < 300,
-
Renal dysfunction: oliguria, serum creatinine level > 2 mg/dL,
-
Hepatic dysfunction: prothrombin time/international normalized ratio (PT/INR) > 1.5,
-
Hematologic dysfunction: platelet count < 100,000/μL.
-
-
-
-
Multi-drug resistant (MDR) organisms (MDRO) are defined as bacteria which are non-susceptible to at least 1 agent in ≥3 antimicrobial categories [40]. The most commonly described MDRO in these guidelines are 3GC-resistant Enterobacteriaceae that are also resistant to fluoroquinolones and sulfonamides.
-
Extensively-drug resistant (XDR) organisms (XDRO) are defined as bacteria which are non-susceptible to at least 1 agent in all but 2 or fewer antimicrobials [40]. The most commonly reported XDRO in these guidelines are the carbapenem-resistant Acinetobacter baumannii, carbapenem-resistant Pseudomonas aeruginosa, and carbapenem-resistant Enterobacteriaceae.
Diagnosis
Radiologic evaluation
Microbiologic evaluation
Biochemical evaluation
Others
Treatment
Principles of therapy
Antibiotic therapy recommendations for peritoneal and intraperitoneal infections
-
Group A Hospitals: have more than 20% 3GC-resistance in nosocomial Enterobacteriaceae and less than 20% resistance to ceftazidime and carbapenems in nosocomial Pseudomonas aeruginosa,
-
Group B Hospitals: have more than 20% 3GC-resistance in nosocomial Enterobacteriaceae and more than 20% resistance to carbapenems in Acinetobacter baumannii,
-
Group C Hospitals: have more than 20% 3G-resistance in nosocomial Enterobacteriaceae and more than 20% resistance to ceftazidime and carbapenems in nosocomial Pseudomonas aeruginosa,
-
Group D Hospitals: have more than 20% resistance to 3GC and carbapenems in nosocomial Enterobacteriaceae.
Type of infection | Classification | Sub-classification | Duration of antimicrobial therapy | Recommendation |
---|---|---|---|---|
Peritoneal/ Intra-peritoneal |
Mild to moderate with hemodynamic stability (no spillage of intraluminal material in the peritoneum)
| Acute stomach or duodenal/ proximal jejunal perforation in the absence of gastric acid-reducing therapy or malignancy, and when the patient is operated within 24 h | 24 h (grade 3A) |
No risk of 3GCRE
-[AMC + AMG (grade 2B)] Or -[3GC (CRO or CTX or ZOX) + MTZ ± AMG (grade 2B)] -No additional antibiotic coverage against Enterococci (grade 1) -No additional antifungal coverage (grade 2B)
Risk of 3GCRE
-ETP (grade 1) or TGC (grade 2B) -No additional antibiotic coverage against Enterococci (grade 1) -No additional antifungal coverage (grade 2B) |
Bowel injuries attributed to penetrating, blunt, or iatrogenic trauma repaired within 12 h without any intraoperative contamination of the operative field by enteric contents | 24 h (grade 1) | |||
Acute appendicitis without evidence of perforation, abscess, local peritonitis, or spillage of intraluminal material in the peritoneum | 24 h (grade 1) | |||
Mild to moderate with hemodynamic stability (with intra-abdominal contamination with intraluminal material)
| Acute stomach or duodenal/ proximal jejunal perforation in case of delayed operation > 24 h, the presence of gastric malignancy or the presence of therapy reducing gastric acidity and the infection is ongoing or persistent | 4–7 d1 (grade 3B) |
No risk of 3GCRE
-[AMC + AMG (grade 2B)] Or -[3GC (CRO or CTX or ZOX) + MTZ ± AMG (grade 2B)] -No additional antibiotic coverage against Enterococci (grade 1) -No additional antifungal coverage (grade 2B)
Risk of 3GCRE
-ETP (grade 1) or TGC (grade 2B) -No additional antibiotic coverage against Enterococci (grade 1) -No additional antifungal coverage (grade 2B) | |
Bowel injuries attributed to penetrating, blunt, or iatrogenic trauma repaired within 12 h (with intra-abdominal contamination with intraluminal material) | 4–7 d1 (grade 3B) | |||
Acute appendicitis (with intra-abdominal contamination with intraluminal material) | 4–7 d1 (grade 3B) | |||
Severe (Appendicitis, colonic non-diverticular perforation, diverticulitis, gastro-duodenal perforations, small bowel perforation, pelvic inflammatory disease, post-traumatic perforation)
| No secondary bacteremia; Adequate source control | 4 d1 (grade 2A) | - CAR (IPM or MEM) (grade 1) - Use glycopeptides for Enterococci treatment in immunocompromised patients or those with recurrent infection (grade 2B) - Antifungal therapy: • FLC as targeted therapy in high risk2, non-septic, immunocompetent patients (grade 2B) • Echinocandins (AFG, CAS or MFG) in septic or immunocompromised patients (grade 3B) | |
Secondary bacteremia; Adequate source control with successful treatment of bacteremia | 7 d1 (grade 2B) | |||
No adequate source control | > 7–14 d1 (grade 3B) | |||
Cholecystitis |
Grade 1
| – | 24 h (grade 1) | AMC (grade 2B) or CXM (grade 2B) or 3GC (CRO or CTX or ZOX) (grade 2A) |
Grade 2
| – | 4–7 d (grade 3B) (adequate source control) |
No risk of 3GCRE
3GC (CRO or CTX or ZOX) + MTZ (grade 2A)
Risk of 3GCRE
ETP (1) or TGC (2B) or TZP (3B) | |
Grade 3
| – | ≥ 5 d 3 (grade 3B) | CAR (IPM or MEM) (1) | |
Cholangitis |
Mild to moderate
| – | 4–7 d 4 (grade 3B) (adequate source control) |
No risk of 3GCRE
3GC (CRO or CTX or ZOX) + MTZ (grade 2A)
Risk of 3GCRE
ETP (grade 1) or TGC (grade 2B) or TZP (grade 3B) |
Severe (including perforation, emphysema, and necrosis of gall bladder, etc.) | – | ≥ 5 d 3,4 (grade 3B) | CAR (IPM or MEM) + glycopeptide (grade 1) |
Type of infection | Classification | Sub-classification | Hospitals Group A (> 20% 3GC resistance in nosocomial Enterobacteriaceae and < 20% resistance to CAZ and CAR in nosocomial P. aeruginosa | Hospitals Group B (> 20% 3GC resistance in nosocomial Enterobacteriaceae and > 20% resistance to CAR in A. baumannii) | ||
---|---|---|---|---|---|---|
Duration of antimicrobial therapy | Recommendation | Duration of antimicrobial therapy | Recommendation | |||
Peritoneal/ Intra-peritoneal |
Mild to moderate with hemodynamic stability (no spillage of intraluminal material in the peritoneum)
| Acute stomach or duodenal/ proximal jejunal perforation in the absence of gastric acid-reducing therapy or malignancy, and when the patient is operated within 24 h | 5 d (grade 2B) | 1- CAR sparing regimen: [(TZP or CAZ or FEP) + TGC] (grade 3B) + Echinocandin (AFG, CAS or MFG) (grade 2A) Or 2- [CAR (IPM or MEM) (grade 3C) + anti-MRSA antibiotics2 (grade 2A)] + Echinocandin (AFG, CAS or MFG) (grade 2A) | 7 d (grade 2B) | If the patient was not on a CAR-containing regimen: [CAR (IPM or MEM) (grade 3C) + anti-MRSA antibiotics1 (grade 2A)] + Echinocandin (AFG, CAS or MFG) (grade 2A) If the patient was on a CAR containing regimen: [(C/T or TZP or CAZ or FEP) + TGC] (grade 3C) + Echinocandin (AFG, CAS or MFG) (grade 2A) *In case of positive XDRO screen, modify antibacterial regimen as per culture results. |
Bowel injuries attributed to penetrating, blunt, or iatrogenic trauma repaired within 12 h without any intraoperative contamination of the operative field by enteric contents | 5 d grade 2B) | 7 d (grade 2B) | ||||
Acute appendicitis without evidence of perforation, abscess, local peritonitis, or spillage of intraluminal material in the peritoneum | 5 d (grade 2B) | 7 d (grade 2B) | ||||
Mild to moderate with hemodynamic stability (with intra-abdominal contamination with intraluminal material)
| Acute stomach or duodenal/ proximal jejunal perforation in case of delayed operation > 24 h, the presence of gastric malignancy or the presence of therapy reducing gastric acidity and the infection is ongoing or persistent | 7–10 d2 (grade 2B) | 1- CAR sparing regimen: [(TZP or CAZ or FEP) + TGC] (grade 3B) + Echinocandin (AFG, CAS or MFG) (grade 2A) Or 2- [CAR (IPM or MEM) (grade 3C) + anti-MRSA antibiotics1 (grade 2A)] + Echinocandin (AFG, CAS or MFG) (grade 2A) | 7–14 d2 (grade 2B) | If the patient was not on a CAR-containing regimen: [CAR (IPM or MEM) (grade 3C) + anti-MRSA antibiotics1 (grade 2A)] + Echinocandin (AFG, CAS or MFG) (grade 2A) If the patient was on a CAR containing regimen: [(TZP or CAZ or FEP) + TGC] (grade 3C) + Echinocandin (AFG, CAS or MFG) (grade 2A) *In case of positive XDRO screen, modify antibacterial regimen as per culture results. | |
Bowel injuries attributed to penetrating, blunt, or iatrogenic trauma repaired within 12 h (with intra-abdominal contamination with intraluminal material) | 7–10 d2 (grade 2B) | 7–14 d2 (grade 2B) | ||||
Acute appendicitis (with intra-abdominal contamination with intraluminal material) | 7–10 d2 (grade 2B) | 7–14 d2 (grade 2B) | ||||
Severe (Appendicitis, colonic non-diverticular perforation, diverticulitis, gastro-duodenal perforations, small bowel perforation, pelvic inflammatory disease, post-traumatic perforation)
| No secondary bacteremia; Adequate source control | 7–14 d2 (grade 2B) | 1- [CAR (IPM or MEM) (grade 1) + Glycopeptide or LZD3 (grade 2B)] + Echinocandin (AFG, CAS or MFG) (grade 2A) Or 2-CAR sparing regimen: [(C/T + MTZ) or (CZA + MTZ) (grade 2B) + Glycopeptide or LZD3 (grade 2B)] + Echinocandin (AFG, CAS or MFG) (grade 2A) | 7–14 d2 (grade 2B) | 1-[CAR (IPM or MEM) + CST + Glycopeptide or LZD3 (grade 3C)] + Echinocandin (AFG, CAS or MFG) (grade 2A) Or 2- CAR sparingregimen: [(TZP or CAZ or FEP) + CST + TGC + Glycopeptide or LZD3 (grade 3C)] + Echinocandin (AFG, CAS or MFG) (grade 2A) *In case of negative XDRO screen or intra-operative cultures for Acinetobacter spp., discontinue colistin. | |
Secondary bacteremia; Adequate source control with successful treatment of bacteremia | 10–14 d2 (grade 2B) | 10–14 d2 (grade 2B) | ||||
No adequate source control | > 10–14 d2 (grade 2B) | ≥ 14 d2 (grade 2B) | ||||
Cholecystitis |
Grade 1
| – | 4 d (grade 2B) | 1- CAR sparing regimen: [(TZP or CAZ or FEP) + TGC] (grade 3B) Or 2- [CAR (IPM or MEM) (grade 3C) + anti-MRSA antibiotics1 (grade 2A)] | 5 d (grade 2B) | If the patient was not on a CAR-containing regimen: [CAR (IPM or MEM) (grade 3C) + anti-MRSA antibiotics1 (grade 2A)] If the patient was on a CAR containing regimen: [(TZP or CAZ or FEP) + TGC] (grade 3C) *In case of positive XDRO screen, modify antibacterial regimen as per culture results. |
Grade 2
| – | 7–10 d (grade 2B) (adequate source control) | 7–10 d (grade 2B) (adequate source control) | |||
Grade 3
| – | ≥ 10 d4 (grade 2B) | ≥ 10–14 d4 (grade 2B) | |||
Cholangitis5,6 |
Mild to moderate
| – | > 7 d4 (grade 3B) | 1- CAR sparing regimen: [(TZP or CAZ or FEP) + TGC] (grade 3B) Or 2- [CAR (IPM or MEM) (grade 3C) + anti-MRSA antibiotics1 (grade 2A)] | 7–10 d (grade 2B) | If the patient was not on a CAR-containing regimen: [CAR (IPM or MEM) (grade 3C) + anti-MRSA antibiotics1 (grade 2A)] If the patient was on a CAR containing regimen: [(TZP or CAZ or FEP) + TGC] (grade 3C) *In case of positive XDRO screen, modify antibacterial regimen as per culture results. |
Severe (including perforation, emphysema, and necrosis of gall bladder, etc.) | – | ≥ 10 d4 (grade 2B) | ≥ 10–14 d4 (grade 2B) |
Type of infection | Classification | Sub-classification | Hospitals Group C (> 20% 3G resistance in nosocomial Enterobacteriaceae and > 20% resistance to CAZ and CAR in nosocomial P. aeruginosa) | Hospitals Group D (> 20% resistance to 3GC and CAR in nosocomial Enterobacteriaceae | ||
---|---|---|---|---|---|---|
Duration of antimicrobial therapy | Recommendation | Duration of antimicrobial therapy | Recommendation | |||
Peritoneal/ Intra-peritoneal |
Mild to moderate with hemodynamic stability
(No spillage of intraluminal material in the peritoneum)
| Acute stomach or duodenal/ proximal jejunal perforation in the absence of gastric acid-reducing therapy or malignancy, and when the patient is operated within 24 h | 7 d (grade 2B) |
If the patient was not on a CAR-containing regimen:
[CAR (IPM or MEM) (grade 3C) + anti-MRSA antibiotics1 (grade 2A)] + Echinocandin (AFG, CAS or MFG) (grade 2A)
If the patient was on a CAR containing regimen:
[(TZP or CAZ or FEP) + TGC] (grade 3C) + Echinocandin (AFG, CAS or MFG) (grade 2A) Or [C/T (grade 3C) + anti-MRSA antibiotics1 (grade 2A)] + Echinocandin (AFG, CAS or MFG) (grade 2A) *In case of positive XDRO screen, modify antibacterial regimen as per culture results. | 7 d (grade 2B) |
If the patient was not on a CAR-containing regimen:
[CAR (IPM or MEM) (grade 3C) + anti-MRSA antibiotics1 (grade 2A)] + Echinocandin (AFG, CAS or MFG) (grade 2A)
If the patient was on a CAR containing regimen:
[(TZP or CAZ or FEP) + TGC] (grade 3C) + Echinocandin (AFG, CAS or MFG) (grade 2A) Or [C/T (grade 3C) + anti-MRSA antibiotics1 (grade 2A)] + Echinocandin (AFG, CAS or MFG) (grade 2A) *In case of positive XDRO screen, modify antibacterial regimen as per culture results.. |
Bowel injuries attributed to penetrating, blunt, or iatrogenic trauma repaired within 12 h without any intraoperative contamination of the operative field by enteric contents | 7 d (grade 2B) | 7 d (grade 2B) | ||||
Acute appendicitis without evidence of perforation, abscess, local peritonitis, or spillage of intraluminal material in the peritoneum | 7 d (grade 2B) | 7 d (grade 2B) | ||||
Mild to moderate with hemodynamic stability (with intra-abdominal contamination with intraluminal material)
| Acute stomach or duodenal/ proximal jejunal perforation in case of delayed operation > 24 h, the presence of gastric malignancy or the presence of therapy reducing gastric acidity and the infection is ongoing or persistent | 7–14 d2 (grade 2B) |
If the patient was not on a CAR-containing regimen:
[CAR (IPM or MEM) (grade 3C) + anti-MRSA antibiotics1 (grade 2A)] + Echinocandin (AFG, CAS or MFG) (grade 2A)
If the patient was on a CAR containing regimen:
[(TZP or CAZ or FEP) + TGC] (grade 3C) + Echinocandin (AFG, CAS or MFG) (grade 2A) Or [C/T (grade 3C) + anti-MRSA antibiotics1 (grade 2A)] + Echinocandin (AFG, CAS or MFG) (grade 2A) *In case of positive XDRO screen, modify antibacterial regimen as per culture results. | 7–14 d2 (grade 2B) |
If the patient was not on a CAR-containing regimen:
[CAR (IPM or MEM) (grade 3C) + anti-MRSA antibiotics1 (grade 2A)] + Echinocandin (AFG, CAS or MFG) (grade 2A)
If the patient was on a CAR containing regimen:
[(TZP or CAZ or FEP) + TGC] (grade 3C) + Echinocandin (AFG, CAS or MFG) (grade 2A) Or [C/T (grade 3C) + anti-MRSA antibiotics1 (grade 2A)] + Echinocandin (AFG, CAS or MFG) (grade 2A) *In case of positive XDRO screen, modify antibacterial regimen as per culture results. | |
Bowel injuries attributed to penetrating, blunt, or iatrogenic trauma repaired within 12 h (with intra-abdominal contamination with intraluminal material) | 7–14 d2 (grade 2B) | 7–14 d2 (grade 2B) | ||||
Acute appendicitis (with intra-abdominal contamination with intraluminal material) | 7–14 d2 (grade 2B) | 7–14 d2 (grade 2B) | ||||
Severe (Appendicitis, colonic non-diverticular perforation, diverticulitis, gastro-duodenal perforations, small bowel perforation, pelvic inflammatory disease, post-traumatic perforation)
| No secondary bacteremia; Adequate source control | 7–14 d2 (grade 2B) | CAR sparing regimen: [C/T + MTZ + AMK ± CST (grade 2B) + Glycopeptide or LZD3 (grade 3C)] + Echinocandin (AFG, CAS or MFG) (grade 2A)
If C/T is not available:
1- CAR sparing regimen: [(TZP or CAZ or FEP) + CST + TGC + Glycopeptide or LZD3 (grade 3C)] + Echinocandin (AFG, CAS or MFG) (grade 2A) Or 2- [CAR (IPM or MEM) + CST + Glycopeptide or LZD3 (grade 3C)] + Echinocandin (AFG, CAS or MFG) (grade 2A) *In case of negative XDRO screen or intra-operative cultures for Pseudomonas spp., discontinue colistin. | 7–14 d2 (grade 2B) |
If MEM MIC ≤ 16 μg/mL:
1-[MEM (DD and prolonged infusion over 4 h) + TGC ± AMK (grade 3C) + Glycopeptide or LZD3 (grade 2A)] + Echinocandin (AFG, CAS or MFG) (grade 2A) Or 2- CAR sparing regimen: [CZA + TGC ± AMK (grade 2B) + Glycopeptide or LZD3 (grade 2A)] + Echinocandin (AFG, CAS or MFG) (grade 2A)
If MEM MIC > 16 μg/mL:
1-[CZA + TGC ± AMK (grade 2B) + Glycopeptide or LZD3 (grade 2A)] + Echinocandin (AFG, CAS or MFG) (grade 2A) Or 2- [dual CAR regimen (MEM + ETP) + CST + TGC ± AMK (grade 3C) + Glycopeptide or LZD3 (grade 2A)] + Echinocandin (AFG, CAS or MFG) (grade 2A) *In case of negative XDRO screen or intra-operative cultures for CRE, discontinue colistin. | |
Secondary bacteremia; Adequate source control with successful treatment of bacteremia | 10–14 d2 (grade 2B) | 10–14 d2 (grade 2B) | ||||
No adequate source control | ≥ 14 d2 (grade 2B) | ≥ 14 d2 (grade 2B) | ||||
Cholecystitis |
Grade 1
| – | 5 d (grade 2B) | 1- CAR sparing regimen: [(TZP or CAZ or FEP) + TGC] (grade 3B) Or 2- [CAR (IPM or MEM) (grade 3C) + anti-MRSA antibiotics1 (grade 2A)] | 5 d (grade 2B) | If the patient was not on a CAR-containing regimen: [CAR (IPM or MEM) (grade 3C) + anti-MRSA antibiotics1 (grade 2A)] If the patient was on a CAR containing regimen: [(TZP or CAZ or FEP) + TGC] (grade 3C) *In case of positive XDRO screen, modify antibacterial regimen as per culture results. |
Grade 2
| – | 7–10 d (grade 2B) (adequate source control) | 7–10 d (grade 2B) (adequate source control) | |||
Grade 3
| – | ≥ 10–14 d4 (grade 2B) | ≥ 10–14 d4 (grade 2B) | |||
Cholangitis5,6 |
Mild to moderate
| – | 7–10 d (grade 2B) | 1- CAR sparing regimen: [(TZP or CAZ or FEP) + TGC] (grade 3B) Or 2- [CAR (IPM or MEM) (grade 3C) + anti-MRSA antibiotics1 (grade 2A)] | 7–10 d (grade 2B) | If the patient was not on a CAR-containing regimen: [CAR (IPM or MEM) (grade 3C) + anti-MRSA antibiotics1 (grade 2A)] If the patient was on a CAR containing regimen: [(TZP or CAZ or FEP) + TGC] (grade 3C) *In case of positive XDRO screen, modify antibacterial regimen as per culture results. |
Severe (including perforation, emphysema, and necrosis of gall bladder, etc.) | – | ≥ 10–14 d4 (grade 2B) | ≥ 10–14 d4 (grade 2B) |
Antimicrobial therapy recommendations for biliary tract infections
Acute pancreatitis
Diagnosis
Classification and complications
-
Mild AP: no organ failure, local or systemic complications,
-
Moderately severe AP: organ failure that resolves within 48 h and/or local or systemic complications without persistent organ failure,
-
Severe AP: persistent organ failure > 48 h,
-
Interstitial edematous AP: acute inflammation of the pancreatic parenchyma and peri-pancreatic tissues, but without recognizable tissue necrosis,
-
Necrotizing AP: inflammation associated with pancreatic parenchymal necrosis and/or peri-pancreatic necrosis. Infected pancreatic necrosis should be considered when the following conditions are present: the necrosis is extensive involving 30% or more of the pancreas, the patient fails to improve, or deteriorates, after 7 to 10 days of appropriate in-hospital care for acute pancreatitis, along with the development of gas in the area of pancreatic necrosis, all this being associated with rising inflammatory markers or persistent fever.
-
Organ failure and other systemic complications
-
Respiratory: PaO2/FiO2 ≤ 300
-
Cardiovascular: systolic blood pressure < 90 mmHg (off inotropic support), not fluid responsive, or pH < 7.3
-
Renal: serum creatinine ≥1.9 mg/dL (170 μmol/L)
-
-
Local complications
-
Acute peri-pancreatic fluid collections
-
Pancreatic pseudocysts
-
Acute necrotic collections
-
Walled-off pancreatic necrosis
-
Management
Antimicrobial therapy considerations (Tables 5 and 6)
-
The decision to give antimicrobials depends upon the severity and complications of AP.
-
The choice of antimicrobials is based upon tissue penetration of the antimicrobial inside the pancreas and susceptibility of the infecting organism to the chosen antimicrobial.
-
Any concomitant extrapancreatic infection, such as, cholangitis, cholecystitis, pneumonia, urinary tract infection, should be promptly treated with antimicrobials (grade 3B).
-
The prophylactic administration of antibiotics is not necessary in mild AP, since the incidence and mortality rates of infectious complications from mild AP are low (grade 2A). (Table 5)
-
The prophylactic administration of antibiotics in severe AP is recommended in the early disease stages (within 72 h of onset) (grade 2B). (Table 5)
-
Antimicrobial therapy is indicated in infected pancreatic necrosis (grade 3B). In this case, initial CT-guided fine needle aspiration (FNA) for Gram stain and culture to guide use of appropriate antibiotics is desirable; alternatively, empiric use of antibiotics should be provided if there is no access to CT FNA (grade 3B).
-
Carbapenems and fluoroquinolones have the best penetration into the pancreatic tissue among antibiotics active against Enterobacteriaceae [45, 46]. Piperacillin/tazobactam has an acceptable pancreatic tissue penetration [47], while both cephalosporins and aminoglycosides have poor pancreatic tissue penetration [46].
-
Based on antimicrobial resistance issues discussed earlier in these guidelines, fluoroquinolones are not recommended as empiric treatment in severe pancreatitis and infected pancreatic necrosis (grade 3B). Instead, carbapenems (imipenem or meropenem) are recommended for empiric therapy in the above stated indications (grade 3B). In cases of proven susceptibility of the recovered organisms to fluroquinolones or piperacillin/tazobactam, then these agents are recommended as targeted, carbapenem-sparing therapy (grade 3B). (Table 5)
-
Routine administration of antifungals is not recommended in AP (grade 3B). This is considered only in case of no response to antibiotics, presence of confirmed infection due to Candida spp., or risk factors for Candida spp. infection.
-
Probiotic administration is not recommended for the prevention of infectious complications in AP (grade 2A).
-
Therapeutic intervention for infected pancreatic necrosis should be performed after 4 weeks of onset, if possible, when the necrosis has been sufficiently walled off (grade 3B). Details of the invasive intervention in pancreatic necrosis are beyond the scope of this manuscript.
Classification | Duration of antimicrobial therapy | Recommendation |
---|---|---|
Mild | No antibiotics (grade 2A) | No antibiotics (grade 2A) |
Severe
| Up to 14 d (grade 3B) | -Empiric therapy: CAR (IPM or MEM) (grade 3B) -CAR sparing regimen: TZP or FQ (if proven antibiotic susceptibility of the recovered organisms) (grade 3B) |
Infected pancreatic necrosis
|
Antimicrobials | Dose |
---|---|
β-lactam/β-lactamase inhibitor combination | |
AMC | 2.2 g IV every 6 h; 2 h infusion timea |
TZP | 4.5 g IV every 6 h; 3 h infusion time |
C/T | 1.5 g IV every 8 h |
CZA | 2.5 g IV every 8 h |
Carbapenems | |
ETP | 1 g IV every 24 h, consider 2 h infusion time |
IPM | 1 g IV every 8 h |
MEM | 1 g IV every 8 h; consider 2 g IV loading dose; 4 h hour infusion time |
Cephalosporins | |
CXM | 1.5 g IV every 8 h |
CRO | 2 g IV every 12–24 h |
CTX | 1–2 g IV every 6–8 h |
ZOX | 1–2 g IV every 8–12 h |
FEP | 2 g IV every 8 h |
CAZ | 2 g IV every 8 h |
Glycylcyclines | |
TGC | 100 mg IV loading dose, then 50 mg IV every 12 h |
Polymyxin | |
Colistimethate sodium | 9 million IU IV loading dose, then 4.5 million IU IV q12 h |
Aminoglycosides | |
GEN | 5–7 mg/kg IV every 24 h |
AMK | 15–20 mg/kg IV every 24 h |
Fluoroquinolones | |
CIP | 400 mg IV every 8–12 h or 500 mg PO every 8–12 h |
LVX | 750 mg every 24 h (IV or PO) |
MOX | 400 mg every 24 h (IV or PO) |
Metronidazole
| 500 mg every 8-12 h or 1500 mg every 24 h (IV or PO) |
Glycopeptides | |
VAN | 25–30 mg/kg IV loading dose, then 15–20 mg/kg IV every 8–12 h; target trough 15–20 mg/dL |
TEC | 12 mg/kg IV every 12 h for 3 doses (loading dose), then 6–12 mg/kg IV every 24 h |
Oxazolidinone | |
LZD | 600 mg every 12 h (IV or PO) |
Azoles | |
FLC | 800 mg IV loading dose then 400 mg IV every 24 h; 2 h infusion time |
Echinocandins | |
CAS | 70 mg IV loading dose first day, then 50 mg IV daily |
MFG | 100 mg daily |
AFG | 200 mg loading dose first day, then 100 IV mg daily |
Duration of antimicrobial therapy in cIAI
-
Location of IAI (extrabiliary, biliary, and pancreatitis),
-
Severity of illness,
-
Adequacy of source control,
-
Whether the infection is community- or hospital- acquired,
-
Whether MDRO/XDRO are among the causative organisms,
-
Clinical response (resolution of fever and leukocytosis, normalization or progressive improvement of the abdominal exam and of gastrointestinal function)