Original Date: 02/2010 Purpose: To maximize antibiotic stewardship for intraabdominal infection in the Precedes: 4/2013

Transcription

1 Division of Acute Care Surgery Clinical Practice Policies, Guidelines, and Algorithms: Antibiotic Therapy: Intra-Abdominal Infections Clinical Practice Algorithm Original Date: 02/2010 Purpose: To maximize antibiotic stewardship for intraabdominal infection in the Precedes: 4/2013 Division of Acute Care Surgery Last Review Date: 8/2017 Introduction Intraabdominal infection is a common problem worldwide. Though patients present with a wide range of causes and various degrees of severity, the basic tenets of treatment remain source control, resuscitation, and antibiotic therapy. 1, 3, 8 However, various components of treatment such as antibiotic choice and duration of antibiotic treatment have been topics of controversy. We aim to update UTH guidelines to reflect recent evidence-based guidelines published by the Surgical Infection Society 3 and by adapting these recommendations to local antimicrobial resistance patterns, drug availability, and costs. Recommendation Summary 1. Antibiotic treatment should be based on stratification of risk of resistant, uncommon, or opportunistic infection. 2. Source control should be obtained expeditiously by surgical or minimally invasive techniques. 3. Intraperitoneal fluid cultures should only be taken for high risk patients. 4. Empiric treatment should be based on risk of hospital or community acquired infection. 5. If tissue or fluid cultures are available, empiric treatment should be deescalated. 6. Timing of onset of antibiotic treatment should be within 1 hour of diagnosis of suspected sepsis. 7. Duration of antibiotic treatment should not exceed 4 days in patients with adequate source control under most clinical circumstances. For unusual cases, clinical judgement should be used. 8. Management of treatment failure No Grade 1 evidence exists for treatment recommendations Do not change antibiotic course if the patient has treatment failure <48hrs after initial source control and undergoes repeat source control procedure. Consider continuing and/or broadening antibiotic treatment if treatment failure occurs >48hrs after initial source control, if there is radiographic evidence of persistent infection Reinstate antibiotic coverage if patient has clinical deterioration after discontinuation of antibiotics. Recommendation One: Risk Assessment 3, 7 Patients should be risk stratified based on: 1. Signs/Symptoms of sepsis or septic shock (based on Surviving Sepsis Campaign Criteria) 2. Comorbidities, including immunocompromised patients 3. Extremes of age 4. Extent of infection 5. Presence of opportunistic/resistant pathogens by colonization or infection 6. Hospitalization length > 48 hours within the past 90 days or those living in long term medical facilities

2 7. Renal replacement therapy with the past 30 day 8. Broad spectrum or IV antibiotics within the past 90 days Recommendation Two: Source Control 3, 7 1. Remove infected fluid and tissue within 24hours (more emergently if signs of sepsis are present) to prevent ongoing contamination unless clear evidence exists to support good outcomes with non-interventional treatment. 2. Use least invasive mode of effective source control. 3. Do not use planned re-laparotomy if adequate source control is achieved at initial operation. Recommendation Three: Cultures 3 1. Collect peritoneal fluid or tissue culture only in high risk patients for identification of pathogen. Recommendation Four: Empiric Antibiotics 3 Use under guidance of antimicrobial stewardship. Broad spectrum antibiotics should be used for higher risk patients and those with serious illness. Community Acquired Low Risk High Risk Empiric regimen cefoxitin and metronidazole piperacillin-tazobactam, or cefepime/metronidazole, or β-lactam allergy ciprofloxacin and metronidazole aztreonam, metronidazole, and vancomycin Anti-pseudomonal Not recommended covered in empiric regimen coverage Anti-enterococcal Not recommended piperacillin-tazobactam, or, or adjunctive ampicillin or vancomycin Antifungal coverage Not recommended Not recommended Extended Spectrum B- lactamase coverage Hospital Acquired Empiric Regimen β-lactam allergy Anti-enterococcal coverage Anti-staphylococcal coverage Antifungal coverage piperacillin-tazobactam, or cefepime/metronidazole, or cefepime/metronidazole, or aztreonam and metronidazole No known VRE: vancomycin VRE: linezolid or daptomycin Risk factors: recent exposure to broad spectrum antibiotics, post-operative infections, severe sepsis/septic shock, known VRE colonization vancomycin, or linezolid or daptomycin (neither commonly used) Risk factors: known MRSA colonization, advanced age, co-morbid medical conditions, previous hospitalization or operation, recent exposure to antibiotics Severe sepsis/septic shock: micafungin

3 Non-severe illness: fluconazole Risk factors: upper GI perforation, recurrent bowel perforation, surgically debrided pancreas, recent prolonged course of broad spectrum antibiotics, positive cultures Antibiotic dosing 1. Standard Dosing recommended for all patients without renal or hepatic failure and for the nonmorbidly obese (Grade 1-B). 2. Use adjusted dosing in patients with significant hepatic or renal dysfunction. Use therapeutic monitoring where applicable (Grade 2-B). 3. Minimize the use continuous infusion or prolonged courses of beta lactam antibiotics and consider use only in critically ill patients or those with resistant gram-negative organisms. Recommendation Five: De-escalation 3 1. Antibiotics should be routinely de-escalated to the narrowest spectrum drug based on culture results, if available. (Grade 1-B) 2. Do not modify antibiotic based on cultures in low risk patients who have had clinical improvement (Grade 1-B) 3. Do modify antibiotics based on cultures in high risk patients if culture reveals organisms resistant to initial antibiotic treatment (Grade 2-B). Recommendation Six: Timing of antibiotic treatment 3, 7 1. Initiate empiric antibiotic therapy within 1 hour of diagnosis for patients with sepsis or septic shock. 2. Re-administer antibiotics within 1 hour before start of source control procedure if 2 half-lives have passed since last dosing. (Grade 1-B) 3, 5, 6, 7, 8 Recommendation Seven: Duration of Treatment 1. Obtain intra-operative cultures for antimicrobial directed therapy in high risk patients. 2. Limit antibiotic treatment to 24 hours for: a. Traumatic bowel perforations controlled within 12 hours (Grade 1-A) b. Gastroduodenal perforations controlled within 24 hours (Grade 1-C) c. Acute or gangrenous appendicitis without perforation (Grade 1-A) d. Acute or gangrenous cholecystitis without perforation (Grade 1-A) e. Ischemic, non-perforated bowel (Grade 1-C). 3. Antimicrobial therapy should be limited to 4 days (96hrs) following definitive source control (Grade 1-A). 4. Limit antimicrobial to 5 7 days in patients who have not had definitive source control of IAI. a. Clinical parameters such as fever, leukocytosis, and adequacy of gastrointestinal function may be useful in determining antibiotic treatment termination Recommendation Eight: Treatment Failure 3 1. Continuation of further antimicrobial treatment beyond 4 days should be considered a. There is clinical evidence of treatment failure and radiographic evidence of persistent inflammation/infection (Grade 2C).

4 b. If the patient has clinical evidence of treatment failure cannot undergo further source control. (Grade 2C). 2. Reinstitution of antimicrobial treatment should be considered if there is clinical evidence of deterioration of clinical status after discontinuation (Grade 2C). 3. Do not change antimicrobial treatment if patients have early treatment failure (within 48hrs of initial treatment failure) if the patient undergoes repeat definitive source control (Grade 2C). 4. Consider changing antimicrobial to alternative drug class if the patient develops late (>48hrs after initial source control) treatment failure (Grade 2C).

5 Drug Dosing and Approximate Cost Per Day Agent Usual dosing, IAI Daily Cost Fluconazole 400mg IV daily $1X Micafungin 100mg IV daily $16X Cefepime 1 gm IV Q6H $3X Ceftriaxone 1gm IV daily $0.3X-$0.7X Cefoxitin 1-2gm IV Q6hrs $2.3X-$6X Meropenem 500 mg IV Q6hrs $1X Vancomycin 2gm IV daily divided $1X-$6X Q6-8hrs Ampicillin/sulbactam 3gm IV Q6hrs $2X Levofloxacin 750mg IV daily $0.5X Ciprofloxacin 400mg IV Q8hrs $3X Piperacillin/tazobactam 3.375gm IV Q6hrs $4X Metronidazole 500mg IV q8hrs $1.2X Linezolid 600mg IV Q12hrs $15X Tigecycline 50mg IV Q12hrs $6X Colistin Max 5mg/kg/day (70kg) $7X (approx.) Polymyxin B Max 25,000/kg/day $7X (approx.) (70kg) Daptomycin Max 280mg/kg/day (70kg) $28X (approx.) Relevant Literature Review We conducted a PubMed search using the terms antibiotics, peritonitis, intraabdominal infection, and sepsis. We limited the literature search to include only randomized trials since 2013 (last update of this document) and focused on the duration of antimicrobial treatment. Additionally, we included guidelines regarding the treatment of intraperitoneal infection with regard to surgical management and specific antibiotic selections. Search Database Search Terms Limits Articles Excluded articles Included articles 1 PubMed Antibiotics and intraabdominal infection and sepsis 10 years, Clinical trial, English, lanuage PubMed Antibiotics and peritonitis, NOT spontaneous 5 years Clinical trial, English language (2 duplicate) 3 PubMed antimicrobial duration and intraabdominal infection 5 years Clinical trial, English language (3 duplicate)

6 Author/ Year Huang/2014 Study Type Prospective cohort Patients Inclusion (n) Criteria 90 Age 20, SIRS, peritonitis treated surgically Payen/2015 RCT 243 Septic shock, peritonitis confirmed by surgery, Sawyer/2015 RCT 518 Comlicated IAI + Temp >38 c, WBC >11k + GI dysfunction. Must have had intervention for source control Rattan/2016 Rattan/2016 Hassinger/2017 Post hoc RCT Post hoc RCT Post Hoc RCT 129 As Sawyer et al + percutaneous drainage as form of source control 112 As Sawyer et al + criteria to diagnose sepsis 279 As Sawyer et al + High risk category (1+ risk factors for treatment failure) identified as Steroid use, colonic source, HAI, APACHE >5, Exclusion Criteria Intervention Outcomes Results Septic shock, life expectancy <72hrs, Child s B/C cirrhosis Patient/NOK refusal to consent, failure to complete treatment Non-adherence to study protocol, viral hepatits, perforated DU treated within 24hrs, iatrogening bowel injury treated within12hrs, nonperforated/gangrenous appendicitis, gangrenous appendicitis without cultured organism, non-perforated intestinal ischemia, infected nec pacreatitis, psbp, PD catheter associated infection, pregnancy, primary skin closure, inadequate source control. As Sawyer et al + the use of source control by methods other than percutaneous drainage As Sawyer et al + patients who do not meet criteria for sepsis As Sawyer et al + nonhigh risk category Procalcitonin based antibiotic duration vs. clinical judgement Post-operative polymyxin hemofiltration Antibiotic tx until resolution of WBC, fever, ileus for a maximum of 10d Vs 4d fixed course Length of treatment, Death, treatment failure, SSI 28d mortality, SOFA score, SSI, recurrent IAI, 30d mortality except SSI (no surgical site) As Sawyer et al. Recurrent IAI, SSI, death Fewer antibiotic days in procalcitonin group (3.4 vs. 6.1, p=0.001), No difference in death, treatment failure, or SSI No difference in mortality (Treatment 27.7% Conventional 19.5%, p=0.14) No difference in mortality No statistical difference in outcomes between long and short course treatment groups No statistical difference in outcomes between long and short course treatment groups No statistical difference in outcomes between long and short course treatment groups Duration of antibiotics not associated with Tx failure. Presence and number of risks independently associated with Tx failure

7 References 1. Hassinger, T. E., Guidry, C. A., Rotstein, O. D., Duane, T. M., Evans, H. L., Cook, C. H.,... Sawyer, R. G. (2017). Longer-Duration Antimicrobial Therapy Does Not Prevent Treatment Failure in High-Risk Patients with Complicated Intra-Abdominal Infections. Surgical Infections, 18(6), Huang, T., Huang, S., Shyu, Y., Lee, C., Jwo, S., Chen, P., & Chen, H. (2014). A Procalcitonin-Based Algorithm to Guide Antibiotic Therapy in Secondary Peritonitis following Emergency Surgery: A Prospective Study with Propensity Score Matching Analysis. PLoS ONE, 9(3). 3. Mazuski, J. E., Tessier, J. M., May, A. K., Sawyer, R. G., Nadler, E. P., Rosengart, M. R.,... Prince, J. M. (2017). The Surgical Infection Society Revised Guidelines on the Management of Intra- Abdominal Infection. Surgical Infections, 18(1), Payen, D. M., Guilhot, J., Launey, Y., Lukaszewicz, A. C., Kaaki, M., Veber, B.,... Robert, R. (2015). Early use of polymyxin B hemoperfusion in patients with septic shock due to peritonitis: a multicenter randomized control trial. Intensive Care Medicine, 41(6), Rattan, R., Namias, N., & Sawyer, R. G. (2016). Patients with Complicated Intra-Abdominal Infection Presenting with Sepsis Do Not Require Longer Duration of Antimicrobial Therapy. Journal of the American College of Surgeons, 223(1), Rattan, R., Allen, C. J., Sawyer, R. G., Askari, R., Banton, K. L., Coimbra, R.,... Namias, N. (2016). Percutaneously drained intra-abdominal infections do not require longer duration of antimicrobial therapy. Journal of Trauma and Acute Care Surgery, 81(1), Rhodes, A., Evans, L. E., Alhazzani, W., Levy, M. M., Antonelli, M., Ferrer, R.,... Dellinger, R. P. (2017). Surviving Sepsis Campaign. Critical Care Medicine, 45(3), Sawyer, R. G., Claridge, J. A., Nathens, A. B., Rotstein, O. D., Duane, T. M., Evans, H. L.,... Popovsky, K. (2015). Trial of Short-Course Antimicrobial Therapy for Intraabdominal Infection. New England Journal of Medicine, 372(21),