Acute Cholangitis. Kelsey Knotts PharmD Candidate Class of 2016

Transcription

1 Acute Cholangitis Kelsey Knotts PharmD Candidate Class of 2016

2 Learning Objectives 1. Describe the mechanism of the development of acute cholangitis 2. Identify common causative organisms in acute cholangitis 3. Select appropriate empiric antibiotic regimen for acute cholangitis

3 Patient Case TL is a 50 year old F s/p LDLTx 8/25/15 for PNCE Her postsurgical stay was complicated by a Klebsiella pneumonia, AKI, and consistently elevated total bilirubin and liver enzymes with leukocytosis. Has indwelling biliary tubes C. diff PCR negative CMV PCR negative Afebrile Many WBC present in RUQ fluid collection during exploratory surgery no growth 5 days Blood cultures on 9/10, 9/19: No growth 5 days

4 PMH and Allergies Past Medical History ESLD secondary to post necrotic cirrhosisethanol (PNCE) Depressive disorder Eating disorder Ulcerative Colitis Cervical cancer (1999) Diverticulitis Chronic bronchitis HLD Heart murmur Allergies Amoxicillin Diarrhea Ciprofloxacin Pain throughout body Metronidazole No reaction listed

5 Medications Acyclovir 400 mg Duotube BID Isavuconazole 372 mg IV Q24H Meropenem 1000 mg IVPB Q8H Mycophenolate mofetil 1000 mg Duotube BID Pantoprazole 40 mg IV BID Prednisone 10 mg Duotube daily SMXTMP 400mg/5mL oral soln 10 ml Duotube QMWF Tacrolimus 2 mg Duotube Q12H Tigecycline 50 mg IV Q12H

6 Antibiotic History Ceftazidime/avibactam for suspected ESBL Kleb. pneumonia (d/c 9/4) Vancomycin for empiric gram positive/mrsa coverage (d/c 9/9) Ceftriaxone for proven ESBL neg. Kleb. pneumonia (d/c 9/10) Caspofungin for empiric fungal coverage (d/c 9/18)

7 Labs (9/10/15) BUN: 92 Cr: 1.3 Glucose: 249 TBili: 22.3 ALT: 337 AST: 240 WBC: 22.4 Hct: 28.5 Hgb: 9.2 PT: 16.9 INR: 1.3 FK: 5.1

8 Acute Cholangitis Primarily caused by bacterial infection in a patient with biliary obstruction Organisms generally ascend from duodenum Most important predisposing factors include biliary obstruction and stasis due to: Biliary calculi Benign stenosis Malignancy UpToDate, Waltham, MA, 2015.

9 Mechanism Barriers Sphincter of oddi Continuous flushing of bacteriostatic bile salts Secretory IgA and biliary mucous prevent adhesion Increased pressure due to obstruction disrupts these barriers and allows bacteria to permeate bile ductules UpToDate, Waltham, MA, 2015.

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11 Microbiology E. coli Klebsiella Enterobacter Enterococcus spp. Bacteroides and clostridium may be present in mixed infections, but rarely sole infecting UpToDate, Waltham, MA, 2015.

12 Treatment Before antibiotics, any obstruction should be resolved Broad spectrum parenteral antibiotics Target colonic bacteria as causative organisms Antibiotics chosen should have good biliary excretion Regardless of initial empiric antibiotics, therapy should be tailored to organisms isolated in blood cultures and their sensitivities J Hepatobiliary Pancreat Surg Jan; 14(1):

13 Treatment: Mild Penicillins/Betalactam Piperacillin/tazobactam (suspected Pseudomonas) Ampicillin/sulbactam J Hepatobiliary Pancreat Surg Jan; 14(1):

14 Treatment: Moderate/Severe First Choices Third and fourthgeneration cephalosporins Ceftriaxone, ceftazidime, cefepime Monobactams Aztreonam One of the above + metronidazole (for anaerobes) Second Choices Fluoroquinolones Ciprofloxacin or levofloxacin Carbapenems Meropenem Imipenem/cilastatin Doripenem J Hepatobiliary Pancreat Surg Jan; 14(1):

15 Case TL presented with leukocytosis, consistently elevated bilirubin and ALT/AST (peak 9/18 452/366) Suggest likely acute cholangitis over acute cellular rejection TL s Antibiotics Meropenem 1000 mg IV Q8H x 14 days Chosen due to severity of disease Tigecycline 50 mg IV Q12H x 14 days VRE/additional GNR coverage

16 Case (9/22): LFTs trending down (ALT/AST: 301/215) though still elevated. WBC trending down (11.0). Stable abdominal discomfort, no worsening. Patient denied repeat liver biopsy. Planned stop date of antibiotics is 9/24 for total 14 days of therapy if she continues to improve

17 References Afdhal N. Acute cholangitis. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, Accessed Sept Tanaka A, Takada T, Kawarada Y, et al. Antimicrobial therapy for acute cholangitis: Tokyo Guidelines. J Hepatobiliary Pancreat Surg Jan; 14 (1):