Infectious Disease I Intraabdominal Infections Courses in Therapeutics

Infectious Disease I: Intraabdominal Infections Courses in Therapeutics and Disease State Management Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Learning Objectives (Slide 1 of 3) • Define and describe the difference between primary, secondary, tertiary, complicated, and uncomplicated intraabdominal infections • Define the terms abscess and peritonitis • Describe the typical microbiology of intraabdominal infections Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Learning Objectives (Slide 2 of 3) • Describe the typical clinical presentation of peritonitis and intraabdominal abscess • Describe the appropriate role of culture and susceptibility information for diagnosis and treatment of intraabdominal infections • Describe the most appropriate drug and nondrug measures to treat intraabdominal infections • Provide examples of antimicrobial agents that would be appropriate to treat a secondary intraabdominal infection such as an appendiceal abscess Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Learning Objectives (Slide 3 of 3) • Describe the appropriate antimicrobial treatment for a primary intraabdominal infection such as peritonitis associated with liver cirrhosis • Describe the proper duration of treatment of an intraabdominal infection given details of the patient condition and type of infection • Describe the proper assessment of patients during treatment of intraabdominal infections. Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Required Reading • Gross AE, Di. Piro JT, Olsen KM. Chapter 92. Intraabdominal Infections. In: Di. Piro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9 e. New York, NY: Mc. Graw-Hill; 2014. • Solomkin JS, Mazuki JE, et. al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin. Infect. Dis. 210; 50: 133– 164. Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Overview (Slide 1 of 2) • Infection contained within the peritoneal cavity or retroperitoneal space • Classification • Generalized or Localized infections • Uncomplicated or Complicated infections • Community or Healthcare associated Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Overview (Slide 2 of 2) • Peritonitis • Primary Peritonitis • Spontaneous Bacterial Peritonitis (SBP) • Infection of peritoneal cavity without a source from the abdomen • Secondary Peritonitis • Source of bacteria is evident from within the abdomen • May involve perforation of the GI tract • Tertiary peritonitis • An infection that persists or recurs at least 48 hours after apparently adequate management of primary or secondary peritonitis • Occurs in critically ill patients • Abscesses • Result of chronic inflammation • Located in the peritoneal cavity or in a visceral organ • Risk factors the same as peritonitis Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Pathophysiology • Primary Peritonitis is due to • Secondary peritonitis is due to bacterial transmigration to the bacterial entry via; • Perforation of the GI tract intraabdominal cavity via; • Bloodstream • Lymphatic system • Transmigration through the bowel wall • Indwelling peritoneal dialysis catheter • Fallopian tubes in females • Perforation of female genital tract • Contamination during a surgical procedure • Anastomotic leak • Abscess begins by the combined action of inflammatory cells bacteria, fibrin, and other inflammatory mediators Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Causes of Bacterial Peritonitis • Primary (spontaneous) bacterial peritonitis • Peritoneal dialysis • Cirrhosis with ascites • Nephrotic syndrome • Secondary bacterial peritonitis (cont. ) • Mechanical GI problems • Any cause of small bowel obstruction (adhesions, hernia) • Vascular causes • Secondary bacterial peritonitis (cont. ) • Miscellaneous causes • • • Diverticulitis Appendicitis Inflammatory bowel diseases Salpingitis Biliary tract infections Necrotizing pancreatitis • Neoplasms • Intestinal obstruction • Perforation • Mesenteric arterial or venous occlusion (atrial fibrillation) • Mesenteric ischemia without occlusion • Iatrogenic intestinal perforation (endoscopy) • Intraoperative events • Blunt abdominal trauma with rupture of intestine • Penetrating abdominal trauma • Leakage from GI anastomosis • Trauma • Solid organ transplant in the abdomen • Peritoneal contamination during abdominal operation Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Normal Flora of GI Tract Approximate Concentration (Log No. Organisms/m. L [× 10 3/L]) Site Stomacha Biliary tract Streptococcus, Lactobacillus 10– 100 Rare Normally sterile (Escherichia coli, Klebsiella, or enterococci in some patients) 0 0 Proximal small bowel Streptococcus (including enterococci), E. coli, Klebsiella, Lactobacillus, diphtheroids 100 Few Distal ileum E. coli, Klebsiella, Enterobacter, enterococci, Bacteroides fragilis, 104– 106 Clostridium, peptostreptococci 105– 107 Colon 105– 108 Bacteroides spp. , peptostreptococci, Clostridium, E. coli, Klebsiella, enterococci, Enterobacter, Candida, and many others 109– 1011 Commonly Found Bacteria Aerobes a. With achlorhydria, acid suppressive therapy, gastric cancer, or gastric outlet obstruction, bacterial counts may rise to 10 5/m. L Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved Anaerobes

Common Pathogens Secondary Peritonitis(%) Gram-Negative Bacteria Escherichia coli Enterobacter Klebsiella Proteus Gram-Positive Bacteria Enterococcus Streptococcus Staphylococcus Anaerobic Bacteria Bacteroides Clostridium Fungi Community-Acquired Infection(%) Nosocomial Infection(%) 32– 61 8– 26 6– 26 4– 23 29 5. 2 2. 8 1. 7 22. 5 8. 0 4. 5 2. 4 18– 24 6– 55 6– 16 10. 6 13. 7 3. 1 18 10 4. 8 25– 80 5– 18 2– 5 13. 7 3. 5 3 10. 3 3. 4 4 Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Primary Peritonitis • Varies greatly between patients • Mild complaints • Acute distress • Symptoms • Nausea • Vomiting • Abdominal tenderness • Signs • • Hypoactive bowel sounds Mild fever Cirrhotic patients may have mental status changes Cloudy dialysate fluid in patients with Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Secondary Peritonitis • Patients are often in acute distress • Symptoms • Nausea and Vomiting • Abdominal guarding • Signs • • • Fever Tachypnea Tachycardia Faint to absent bowel sounds Sepsis Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Laboratory, Radiology, and Microbiology • Laboratory • WBC • Ascitic Fluid • Increase in Leukocytes • Radiology • Abdominal radiographs • Microbiology • Gram stain and Cultures of ascitic fluid Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Goals of Therapy • Correction of the intraabdominal disease processes or injuries that have caused infection • Drainage of purulent collections • Achieve a resolution of infection without major organ system complications • Ameliorate clinical signs and symptoms • Provide supportive care Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

General Approach to Treatment • Surgical intervention and prompt drainage of abscesses • Support of vital functions • Early administration of empiric antibiotics that cover • Gram negatives • Anaerobes Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Nonpharmacological Treatment • Surgical correction of underlying pathology • Respiratory and circulatory support as needed • Aggressive fluid resuscitation therapy Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

General Approach to Empiric Antibiotic Therapy (Slide 1 of 3) • Primary Bacterial Peritonitis • Cirrhosis • Most Frequent bacteria • E. coli • Klebsiella spp. • Streptococci spp. • Antibiotic Coverage choices • 3 rd Generation Cephalosporin • Ceftriaxone • Cefotaxime • Ampicillin/Sulbactam • Β-lactam allergy • Ciprofloxacin IV • Trimethoprim/sulfamethoxazole IV • Optional add anaerobic coverage • Metronidazole Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

General Approach to Empiric Antibiotic Therapy (Slide 2 of 3) • Primary Bacterial Peritonitis • Peritoneal Dialysis • Most Frequent bacteria • Staphylococcus aureus • MSSA • MRSA • Streptococci spp. • Gram negative enteric pathogens rare • Antibiotic Coverage choices • Combinations • Cefazolin plus [Cefazidime or Cefepime or Aminoglycoside] • Single Agents • Cefepime • Imipenem/cilastatin • Β-lactam allergy • Vancomycin plus aminoglycoside • Ciprofloxacin (if local susceptibilities allow) Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

General Approach to Empiric Antibiotic Therapy (Slide 3 of 3) • Primary Bacterial Peritonitis • Peritoneal Dialysis • • • Symptom onset slower which allows for gram stains and cultures MSSA • Cefazolin IV • Nafcillin/ oxacillin IV • Β-lactam allergy • Vancomycin IV • Linezolid IV • Daptomycin IV MRSA: • Vancomycin in peritoneal dialysate • Vancomycin IV • Linezolid IV • Daptomycin IV Streptococcus or Enterococcus • Ampicillin • Β-lactam allergy • Vancomycin IV • Linezolid IV Gram negative Bacteria: • Ceftazidime or cefepime Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Primary Bacterial Peritonitis Treatment Course • Primary Bacterial Peritonitis • Deescalate antibiotics when cultures are finalized • Oral agents can be used to complete the treatment • Treatment Duration • Traditional 10 to 14 days • Peritoneal Dialysis patient should be treated for 14 days • Prevention • High reoccurrence rate of peritonitis in patients with cirrhosis • Decrease in mortality and infection rate • Antibiotic regimens • Trimethoprim/sulfamethoxazole DS 1 tab PO daily for 5 days of the week • Norfloxacin 400 mg PO Daily • Ciprofloxacin 750 mg weekly or 500 mg Daily Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

General Approach to Empiric Antibiotic Therapy: Secondary Bacterial Peritonitis • • • Perforated GI Tract Abscess Appendicitis Most frequent bacteria depends where perforation/ infection occurs Antibiotic Coverage choices • Community-Acquired Complicated Intra-abdominal Infections • Mild to Moderate infections • High Severity Infections • Hospital-Acquired Complicated Intra-abdominal Infections Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Empiric Antibiotics for Mild to Moderate Severity Community Acquired Intraabdominal Infections (Slide 1 of 3) • Therapy should be active against • Enteric gram-negative aerobic and facultative bacilli • Enteric gram-positive streptococci • Coverage for anaerobic bacteria should be provided for distal small bowel, appendiceal, and colon-derived infections • Combination or Monotherapy can be used • Avoid anti-pseudomonal agents Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Empiric Antibiotics for Mild to Moderate Severity Community Acquired Intraabdominal Infections (Slide 2 of 3) • Mono-therapy • β-lactam/β-lactamase inhibitor therapy • Ticarcillin/ clavulanate • Cephalosporins • Cefoxitin • Carbopenems • Ertapenem • Fluoroquinolones • Moxifloxacin • Glycylcyclines • Tigecycline Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Empiric Antibiotics for Mild to Moderate Severity Community Acquired Intraabdominal Infections (Slide 3 of 3) • Combination therapy • • Cefazolin plus metronidazole Cefuroxime plus metronidazole Ciprofloxacin plus metronidazole Levofloxacin plus metronidazole Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Empiric Antibiotics for High Risk Community Acquired Intraabdominal Infections (Slide 1 of 3) • High Risk patients should be covered for Pseudomonas aeruginosa • High Risk Patients • • • High APACHE II Scores Poor nutritional Status Cardiovascular disease Immunosuppression Prolonged hospital stay Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Empiric Antibiotics for High Risk Community Acquired Intraabdominal Infections (Slide 2 of 3) • Mono-therapy • Β-lactam/β-lactamase inhibitor therapy • Piperacillin/tazobactam • Carbopenems • Meropenem • Imipenem/cilastatin • Doripenem Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Empiric Antibiotics for High Risk Community Acquired Intraabdominal Infections (Slide 3 of 3) • Combination Therapy • • Cefepime plus metronidazole Ceftazidime plus metronidazole Ciprofloxacin plus metronidazole Levofloxacin plus metronidazole Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Empiric Antibiotics for High Risk Hospital Acquired Intraabdominal Infections • Patients that have risk factors for Multi drug resistant bacteria • See Empiric Antibiotic lecture for list of risk factors • Pseudomonas aeruginosa • Use antipseudomonal agents • If high resistance at institution consider double coverage • Extended Spectrum β-lactamase producers • MRSA Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Secondary Bacterial Peritonitis Treatment Course • Deescalate antibiotics when cultures are finalized • Oral agents can be used to complete the treatment • Treatment Duration • Traditional 5 to 10 day courses Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Clinical Outcomes • Improvement in clinical signs and symptoms 2 -3 days after antibiotics initiated • Resolution of WBC • Afebrile Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

Summary • Intra-abdominal infections occur in the peritoneal cavity • Empiric antibiotic therapy should be directed at gram negative and anaerobic pathogens • Patient with alcoholic cirrhosis are at high risk for SBP caused by gram negative pathogens • Patients with peritoneal dialysis are at risk for SBP caused by gram positive skin flora • Patients with exposure to health care will require broadened empiric antibiotic coverage Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved

References • Gross AE, Di. Piro JT, Olsen KM. Chapter 92. Intraabdominal Infections. In: Di. Piro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey L. eds. Pharmacotherapy: A Pathophysiologic Approach, 9 e. New York, NY: Mc. Graw-Hill; 2014. • Solomkin JS, Mazuki JE, et. al. Diagnosis and management of complicated intra-abdominal infection in adults and children: guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clin. Infect. Dis. 210; 50: 133– 164. Author: Michael W. Perry Pharm. D, BCPS, BCCCP; Assistant Clinical Professor of Pharmacy Practice; Mylan School of Pharmacy http: //accesspharmacy. mhmedical. com/Learning. Module. Group. aspx? id=8 Copyright © 2017 Mc. Graw-Hill Education. All rights reserved