Antimicrobial Therapy

2. Antimicrobial Therapy • TOKYO GUIDELINES • Tokyo International Consensus Meeting • April 1-2, 2006 • @ Keio Plaza Hotel, Tokyo, Japan • Japan, Singapore, Korea, HongKong, China, Taiwan, Argentina, Germany, South Africa, Italy, France, USA, Indonesia, Australia, Thailand, Malaysia, New Zealand, Philippines (S.C. Hilvano: Department of Surgery, College of Medical & Philippine General Hospital)

3. Antimicrobial Therapy • INDICATION • Antimicrobial agents should be administered to all patients diagnosed as having acute cholangitis (recommendation A); the Antimicrobial agents should be administered as soon as the diagnosis of acute cholangitis is suspected or established.

4. Antimicrobial Therapy • Most important FACTORS FOR CONSIDERATION: • Antimicrobial activity against causative bacteria • Severity of cholangitis • Presence/absence of renal and hepatic disease • Past history of antimicrobial administration to the patient • Local susceptibility patterns (antibiogram) of the suspected causative organisms • Biliary penetration of the antimicrobial agents.

5. Antimicrobial Therapy • SELECTION • Antimicrobial drugs should be selected according to the severity assessment (recommendation A). • Empirically administered antimicrobial agents should be changed for more appropriate agents according to the identified causative microorganisms and their sensitivity to antimicrobials (recommendation A).

6. Antimicrobial Therapy

7. Antimicrobial Therapy • DOSAGE • According to local rules and regulations • Drug dosage adjustment should be done in patients with decreased renal function. The Sanford guide to antimicrobial therapy and Goodman and Gilman’s the pharmacological basis of therapeutics should be consulted (recommendation A).

8. Antimicrobial Therapy • DURATION • For patients with moderate (grade II) or severe (grade III) acute cholangitis, antimicrobial agents should be administered for a minimum duration of 5–7 days. More prolonged therapy could be required, depending on the presence of bacteremia and the patient’s clinical response, judged by fever, white blood cell count, and C-reactive protein, when available (recommendation A). • For patients with mild (grade I) acute cholangitis, the duration of antimicrobial therapy could be shorter (2 or 3 days) (recommendation A).

9. Antimicrobial Therapy • BILIARY PENETRATION • Biliary penetration should be considered in the selection of antimicrobial agents in acute cholangitis (recommendation A).

10. Ascending Cholangitis Principles of Management Septic Shock • Close monitoring (vital signs, I/O) • Hemodynamic support with IV fluids and vasopressors • Identify underlying cause for sepsis • ABC assessment • IV Fluid resuscitation with crystalloids (e.g. plain NSS) • Parenteral antibiotics • Biliary decompression (severe cases) • Extracorporeal shockwave lithotripsy (ESWL) for choleliths

11. MANAGEMENT

12. MANAGEMENT

13. PROGNOSIS • more serious than cholecystitis, potentially life-threatening • prognosis depends on cause (best to worst) - stones, benign strictures, sclerosing cholangitis, cancer

14. Complications Looking Ahead – Ascending Cholangitis Prognosis • Depends on the following: • Early recognition and treatment of cholangitis • Response to therapy • Underlying medical conditions of the patient • Mortality rate: 5-10%, (higher in patients who require emergency decompression or surgery) • Good response to antibiotics = good prognosis • Liver failure, hepatic abscess, microabscess • Acute renal failure • Bacteremia, sepsis (gram-negative)

15. Complications Looking Ahead – Septic Shock Prognosis • Depends on the following: • Severity of illness • Co-morbidities • Age • Response to antibiotics • Acute respiratory distress syndrome (ARDS) • Renal dysfunction • Disseminated intravascular coagulation (DIC) • Mesenteric ischemia • Myocardial ischemia and dysfunction

16. EXTRA SLIDES MIMI’S NOTES

17. MANAGEMENT Medications: • antibiotics active against enteric organisms • treatment guidelines from The Medical Letter for intra-abdominal infections reasonable first choices • piperacillin-tazobactam (Zosyn) • ticarcillin-clavulanate (Timentin) • ampicillin-sulbactam (Unasyn) • carbapenem - ertapenem, imipenem/cilastatin, or meropenem • Reference - Clin Infect Dis 2003 Oct 15;37(8):997 • previous options no longer recommended cefoxitin (Mefoxin) no longer reliable for Bacillus fragilis • cefotetan (Cefotan) withdrawn from market • some clinicians prefer piperacillin-tazobactam or ampicillin-sulfactam, with or without aminoglycoside, for bacteremia from biliary tract • options if allergic to beta-lactams • fluoroquinolone (ciprofloxacin, levofloxacin or moxifloxacin) plus metronidazole • tigecycline • in severely ill patients • cover Pseudomonas with piperacillin-tazobactam, imipenem, meropenem, ceftazidime, cefepime, aztreonam or ciprofloxacin • add metronidazole for B. fragiliscoverage • aminoglycoside can be added • Reference - Treat Guidel Med Lett 2007 May;5(57):33TOC

18. tigecycline (Tygacil) • tigecycline (Tygacil) FDA approved for IV treatment of complicated intra-abdominal infections and complicated skin and skin structure infections in adults • broad spectrum of activity including methicillin-resistant Staphylococcus aureus (MRSA) • may be used as empiric monotherapy for complicated appendicitis, infected burns, intra-abdominal abscesses, deep soft tissue infections, and infected ulcers • Reference - Infection Control Today 2005 Jun 16 • tigecycline not very effective against Pseudomonas (Prescriber's Letter 2005 Jul;12(7):38) • tigecycline should be used judiciously to reduce resistance, could be useful for resistant organisms but not Pseudomonas (The Medical Letter 2005 Sep 12;47(1217):73)

19. COMPLICATIONS • Complications: • bacterial cholangitis led to sclerosing cholangitis in case report (BMC Gastroenterology 2002 Jun 3;2:14) • Associated conditions: • bile stasis • renal dysfunction and failure common with toxic cholangitis(1)

20. Source: http://emedicine.medscape.com/article/774245-media

21. SOURCES 2007 2007 http://www.springerlink.com/content/j086279743640824/ Flowcharts for the diagnosis and treatment of acute cholangitis and cholecystitis: Tokyo Guidelines Fumihiko Miura, Tadahiro Takada, Yoshifumi Kawarada, Yuji Nimura, Keita Wada, Masahiko Hirota, Masato Nagino, Toshio Tsuyuguchi, Toshihiko Mayumi and Masahiro Yoshida, et al. Journal of Hepato-Biliary-Pancreatic Surgery Volume 14, Number 1, 27-34 • http://www.springerlink.com/content/k4170w575664l851/ • Antimicrobial therapy for acute cholangitis: Tokyo Guidelines • Atsushi Tanaka, Tadahiro Takada, Yoshifumi Kawarada, Yuji Nimura, Masahiro Yoshida, Fumihiko Miura, Masahiko Hirota, Keita Wada, Toshihiko Mayumi and Harumi Gomi, et al. • Journal of Hepato-Biliary-Pancreatic Surgery • Volume 14, Number 1, 59-67

22. 2008 2007 http://www.springerlink.com/content/348u1125q02g1h08/ Diagnostic criteria and severity assessment of acute cholangitis: Tokyo Guidelines Keita Wada, Tadahiro Takada, Yoshifumi Kawarada, Yuji Nimura, Fumihiko Miura, Masahiro Yoshida, Toshihiko Mayumi, Steven Strasberg, Henry A. Pitt and Thomas R. Gadacz, et al. Journal of Hepato-Biliary-Pancreatic Surgery Volume 14, Number 1, 52-58 • http://www.springerlink.com/content/a8v37tr741175070/ • Review Paper • Microbiology and Management of Abdominal Infections • Itzhak Brook • Digestive Diseases and Sciences • Volume 53, Number 10,

23. https://secure.muhealth.org/~ed/students/articles/MLT_57.pdf • http://www.ebscohost.com/dynamed/default.php

24. http://www.idsociety.org/Content.aspx?id=16201