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)

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.

Antimicrobial Therapy

• Most important FACTORS FOR CONSIDERATION:1. Antimicrobial activity against causative bacteria2. Severity of cholangitis3. Presence/absence of renal and hepatic disease4. Past history of antimicrobial administration to the

patient5. Local susceptibility patterns (antibiogram) of the

suspected causative organisms6. Biliary penetration of the antimicrobial agents.

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).

Antimicrobial Therapy

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).

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).

Antimicrobial Therapy

• BILIARY PENETRATION– Biliary penetration should be considered in the

selection of antimicrobial agents in acute cholangitis (recommendation A).

Principles of Management

Septic Shock Ascending Cholangitis

10

• 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

MANAGEMENT

MANAGEMENT

PROGNOSIS

• more serious than cholecystitis, potentially life-threatening

• prognosis depends on cause (best to worst) - stones, benign strictures, sclerosing cholangitis, cancer

Looking Ahead – Ascending Cholangitis

Prognosis Complications• 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)

Looking Ahead – Septic Shock

Prognosis Complications• 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

EXTRA SLIDES

MIMI’S NOTES

MANAGEMENTMedications: • 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. fragilis coverage– aminoglycoside can be added

• Reference - Treat Guidel Med Lett 2007 May;5(57):33 TOC

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)

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)

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

SOURCES

2007• http://www.springerlink.com/con

tent/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

2007• http://www.springerlink.com/conte

nt/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

2008• http://www.springerlink.com/

content/a8v37tr741175070/• Review Paper• Microbiology and

Management of Abdominal Infections

• Itzhak Brook• Digestive Diseases and Science

s

• Volume 53, Number 10,

2007• http://www.springerlink.com/con

tent/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.ebscohost.com/dynamed/default.php

• https://secure.muhealth.org/~ed/students/articles/MLT_57.pdf

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