2028. 05.27.1652 hitpslemedicine medscape.comvatce/1926162-prin ‘emedicine.medscape.com Medscape Antibiotic Therapy for Peritonitis Updated: Jul 22, 2019 Author: Vinay K Kapoor, MBBS, MS, FRCSEd, FICS, FAMS; Chief Editor: BS Anand, MD Treatment Overview Peritoneal infections are classified as primary, secondary, or tertiary. Primary peritoneal infections arise from hematogenous dissemination, usually inthe setting of an immunocompromised state, while secondary infections aro related to a pathologic process in an abdominal organ, such as perforation, ischemia and gangrene, trauma, or a postoperative problem, such as anastomotic leak. Tertiary peritoneal infection is a persistent or recurrent infection that exists after an adequate inital therapy for, secondary peritonitis, Antibiotic therapy is used to prevent local and hematogenous spread of an intra-abdominal infection and to reduce late complications,[1] Several diferent antibiotic regimens are available for the treatment of intra-abdominal infections (see Table 1 below) [1] ‘Single-agent, broad-spectrum therapy and combination therapies have been used against these infections, although no specific therapy has been found to be superior to another. Infection of the abdominal cavity requires coverage for gram-negative and gram-positive bacteria, as well as for anaerobes. ‘Antipseudomonal coverage is recommended for patients who have had previous treatment with antibiotics or who have had a prolnged hospitalization or any intervention. {2} In case of severe infections with features of systemic sepsis, a policy of “hit early and hit hard! (starting therapy as soon as infection is suspected with broad spectrum antibiotics) reduces the mortality of infection, Choice of antibiotics largely depends on whether the infection is community acquired or hospital acquired (nosocomial), the local ‘spectrum of organisms grown and their sensitivity to antibiotics (antibiogram) in similar patients in the near past, costs and side effects of the antibiotics, and comorbidities (especially renal and liver dysfunction) in the patient. Usually, in patients with intra-abdominal infection who have been treated with proper source control and prompt surgical intervention, antibacterial therapy is given for 5-7 days, but this regimen may need to be extended, depending on the clinical situation {1} Shorter courses also have been used successfully. Antibiotics can be discontinued once the clinical signs of infection (eg, fever, tachycardia, leukocytosis) have resolved. Recurrence is a concern with certain infections, such as those with Candida and Staphylococcus aureus, and treatment should be continued for 2-3 weeks. Table 1. Proposed Empirical Antimicrobial Therapy (Open Table in @ new window) Monotherapy Combination Therapy Beta-lactam/Beta-lactamase inhibitor combination Cephalosporin-based Amoxicilinlavulanic acid Cefuroxime + metronidazole Piperacilintazobactam Third- or fourth-generation cephalosporin + metronidazole hitpslemacicine medscape.com/artce!1926162-print 162028. 05.27.1652 hitpslemedicine, medscape.convartce/1926162-prin Ticarcilinclavulanic acid Cefoperazone/sulbactam Carbapenems Quinolone-based Ertapenem Ciprofloxacin + metronidazole Imipenemicilastatin Imipenemicilastatinrelebactam Meropenem ‘Aminoglycoside-based Aminoglycoside + clindamycin Other Other Tigecycline ‘Aztreonam + metronidazole ‘See Peritonitis and Abdominal Sepsis and Surgical Approach to Peritonitis for more complete information on these topics. Enterococcal Coverage In patients with community-acquired peritonitis, coverage for Enterococcus is not recommended. Enteracoccal coverage may be warranted in patients with septic shack who have received prolonged cephalosporin therapy, in patients who are immunosuppressed and are at risk for bacteremia, in patients with prosthetic heart valves, and in patients with recurrent intra- ‘abdominal infections accompanied by severe sepsis.{1] Patients with intra-abdominal contamination are at a high risk for candidiasis, and this has led to the increased use of antifungal prophylaxis. Patients who are immunocompromised or who have received long-term, broad-spectrum antibiotic therapy (eg, patients with severe acute necrotizing pancreatitis) or steroid therapy are predisposed to candidal infections, Other predisposing factors include gastric acid suppressive therapy, central venous catheterization and intravenous hyperalimentation, malnutrition, and diabetes. Infection in the Critically Ill hitpslemacicine medscape.com/artcle!1926162-print 2162028. 05.27.1652 hitpslemedicne, medscape.comvatice/1926162-prin Candida albicans is most commonly isolated from the peritoneum in critically il patients with culture-proven intra-abdominal infections and preoperative Acute Physiology and Chronic Health Evaluation Il (APACHE II) scores of greater than or equal to 16. ‘Additional common peritoneal organisms in this patient population are Enterococcus and Enterobacter species and ‘Staphylococcus epidermidis. These data suggest that the microbiology of intra-abdominal infections may be inherently different in severely ill patients and that broader antimicrobial, and possibly antifungal, coverage may be warranted in these cases, Spontaneous Bacterial Peritonitis ‘Spontaneous bacterial peritonitis (SBP) resulting from chronic liver disease or nephritic syndrome with no obvious source of infection is the most common etiology of primary peritonitis. Untreated SBP has a mortality rate of up to 60%, but with prompt diagnosis and treatment of the condition, this figure may be reduced to 20%. Empiric therapy with a third-generation ‘cephalosporin must be started promptly [3] SBP usually does not require any surgical intervention, ‘The patient with SBP is also likely to require attention to changes in hemodynamic function related to inflammatory pathways, as well as resultant renal function impairment, although a discussion of this is beyond the scope of this article. Specific agents The infection in SBP is usually monomicrobial and most commonly caused by Escherichia coll Initial coverage should include gram-negative enteric bacteria and gram-positive cocci, which are responsible for 90% of infections 4) Cefotaxime is effective against 98% of causative organisms and is considered the treatment drug of choice. ‘Anaerobic, pseudomonal, and staphylococcal coverage is not needed. Cefotaxime (2 g IV qBh) has been shown to achieve excellent ascitic fuid levels. The dosing interval may need to be reduced in patients with renal insufficiency. ‘Amoxicilin-clavulanic acid has been shown to be as effective as cefotaxime; however, a parenteral formulation is not available in the United States [5] Oral ofloxacin has been reported to be as effective as cefotaxime in the treatment of SBP. Ofloxacin should not be given to patients who are vomiting, in shock, bleeding, or in renal failure. Alternatively, intravenous ciprofloxacin (200 mg q12h for 2 d), followed by oral ciprofloxacin (500 mg q12h for § d), has been used successfully. To prevent fluoroquinolone resistance, these antibiotics should not be used empirically to treat SBP. When cultures identify a particular pathogen, susceptibility testing allows the clinician to narrow the spectrum of the antibiotic. Duration of therapy The optimal duration of therapy is not known. In patients without shock, ileus, hepatic coma, andlor renal failure, SBP usually resolves within 2-5 days of starting cefotaxime therapy. Traditionally, a course of 10 days is recommended, although studies have suggested that 5 days of therapy (with documentation of a decrease of peritoneal fluid WBC count to < 250 cells/yL) may be sufficient in most cases. Surgical intervention is not required; in rare cases, laparoscopic lavage may have to be performed if there is no response after adequate antibiotic therapy. Special circumstances Renal impairment occurs in 33% of patients with SBP.{5] Albumin infusion with cefotaxime has been shown to improve survival, compared with the use of cefotaxime alone [6] Avoid aminoglycosides in patients with liver disease, because these patients are at an increased risk for nephrotoxicity. Relapse ‘The risk of rotapse after SBP is high (40-70% in 12 mo); various prophylactic antibiotic regimens are available. A preliminary study found that long-term norfloxacin (400 mg/d) was effective for secondary prevention of SBP{7] Secondary and Tertiary Peritonitis hitpslemacicine medscape.com/artcle!1926162-print ais2028. 05.27.1652 hitps lemedicine medscape.comvaticle/1926162-prin In secondary peritonitis, systemic antibiotic therapy is the second mainstay of treatment following source control (eg, removal of appendix, closure of perforation, resection of gangrenous bowel, drainage of abscess),[8, 9, 10] Several studies suggest that antibiotic therapy is not as effective in the later stages of infection and that early (preoperative) systemic antibiotic therapy can significantly reduce the concentration and growth rates of viable bacteria in the peritoneal fluid. Antibiotic therapy begins with empiric coverage (effective against common gram-negative and anaerobic pathogens), which should be initiated as soon as possible, with a transition made to narrower-spectrum agents (step down approach) as culture results become available, Tertiary peritonitis is persistent, residual, or recurrent peritoneal infection after adequate source control and antibiotic therapy of secondary peritonitis, t manifests as prolonged systemic inflammatory response syndrome (SIRS), sepsis, and septic shock Multiple organ dysfunction syndrome (MODS) associated with tertiary peritonitis responsible for its high mortality. Diagnosis is established with imaging (ie, computed tomography scanning). Opportunistic, nosocomial and facultative pathogenic organisms (eg, enterococci and enterobacter) and fungi are usually involved. Treatment is largely with antibiotics and antifungals; nonsurgical intervention in the form of image-guided percutaneous catheter drainage may be required if there are any collections. Specific conditions and effective agents Perforations of upper Gl tract organs are associated with gram-positive bacteria, whereas distal small bowel and colon perforations involve polymicrobial aerobic and anaerobic species. Antibiotic therapy appears to be less effective in tertiary peritonitis than in other forms of peritonitis. Resistant and unusual ‘organisms (eg, Enterococcus, Candida, Staphylococcus, Enterobacter, Pseudomonas species) are found in a significant proportion of cases. ‘Culture results may be espacially important in tertiary peritonitis, which is more likely to involve gram-positive bacteria {enterococe!); antibiotic-resistant, gram-negative bacteria; and yeast. In community-acquired infections, a second- or third- 24-48 h, return of the white blood cell [WBC] count to the reference range levels) Dangers of prolonged therapy ‘Some patients demonstrate persistent signs of inflammation without a defined infectious focus. In these patients, continued broad-spectrum antibiotic therapy may be more harmful than beneficial (eg, may promote emergence of resistant organisms or Clostridium difficile colts), and a trial of antibiotic therapy cossation under close surveillance may be warranted. Intra-abdominal abscess Antibiotics alone are seldom sufficient to treat intra-abdominal abscesses, and adequate drainage (image-guided percutaneous catheter drainage or surgical drainage) of the abscess is of paramount importance. For most of the commonly used antibiotics, ‘drug levels achieved in the abscess fluid are generally below the minimum inhibitory concentration90 (MIC9O) for Bacteroides fragilis and Escherichia coli, and repeated dosing or high-dose therapy does not improve penetration significantly Contributor Information and Disclosures ‘Author Vinay K Kapoor, MBBS, MS, FRCSEd, FICS, FAMS Professor of HPB Surgery, Mahatma Gandhi Medical College and Hospital (MGMCH), Jaipur, India Vinay K Kapoor, MBBS, MS, FRCSE¢, FICS, FAMS is a member of the following medical societies: Association of Surgeons of India, Indian Association of Surgical Gastroenterology, Indian Society of Gastroenterology, Medical Council of India, National ‘Academy of Medical Sciences (India), Royal College of Surgeons of Edinburgh Disclosure: Nothing to disclose. Chief Editor BS Anand, MD Professor, Department of Internal Medicine, Division of Gastroenterology, Baylor College of Medicine BS Anand, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American Gastroenterological Association, American Society for Gastrointestinal Endoscopy Disclosure: Nothing to disclose. Additional Contributors Michael H Piper, MD Clinical Assistant Professor, Department of Internal Medicine, Division of Gastroenterology, Wayne Stato University Schoo! of Medicine; Consulting Staff, Digestive Health Associates, PLC Michael H Piper, MD is a member of the following medical societies: Alpha Omega Alpha, American College of Gastroenterology, American College of Physicians, Michigan State Medical Society Disclosure: Nothing to disclose. Ketul R Patel, MD Resident, Department of Internal Medicine, Providence Hospital Kotul R Patel, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Medical Association Disclosure: Nothing to disclose. hitpslemacicine medscape.com/artcle!1926162-print 562028. 05.27.1652 hitpslemedicine medscape.comvatce/1926162-prin Bradley J Warren, DO, FACG, FACOI Consulting Staff, Digestive Health Associates, PLC Bradley J Warren, DO, FACG, FACOI is a member of the following medical societies: American College of Gastroenterology, American Osteopathic Association, American Society for Gastrointestinal Endoscopy Disclosure: Nothing to disclose. Acknowledgements Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference Disclosure: Medscape Reference Salary Employment References 41.Blol S, De Waele JJ. 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