Treatment of Complicated IAI

Intra-abdominal infection (IAI) is an important cause of morbidity and mortality

the second most commonly identified cause of severe sepsis in the intensive care unit (ICU)

Most IAI are a result of processes involving inflammation and perforations of the gastrointestinal tract, such as appendicitis, peptic ulcer disease, and diverticulitis.

Introduction

Lopez, Nicole, et al. 2011. A Comprehensive review of abdominal infections. World Journal of Emergency Surgery

IAI include the following pathological conditions:Infections of single organs (cholecystitis,

appendicitis, diverticulitis, cholangitis, pancreatitis, salpingitis, etc.), which can be or not be complicated by peritonitis even in the absence of perforation

Peritonitis (primary, secondary or tertiary)Intra-abdominal abscesses classified on the

basis of their location and anatomic configuration.

Definition

• Menichetti, F.; Et Al. 2009. Definition And Classification Of Intra-abdominal Infections. Journal Of Chemotherapy.

Classification

Peracci, F.M. et al. 2007. Management Of Severe Sepsis Of Abdominal Origin. Scandinavian Journal of Surgery.

Uncomplicated abdominal infections the infectious process is contained within a single organ

Complicated abdominal infections (cIAI) disease is extended, with either localized or generalized peritonitisPrimary peritonitis, Secondary peritonitis,

Tertiary peritonitis, & Intra-abdominal sepsis2 types : Community (can be mild or serious)

& Hospital cIAI (usually occur as post-operative infections)

Classification

• Lopez, Nicole, et al. 2011. A Comprehensive review of abdominal infections. World Journal of Emergency Surgery

• Menichetti, F.; Et Al. 2009. Definition And Classification Of Intra-abdominal Infections. Journal Of Chemotherapy.

• Blot, Stijn. Et al. 2012. Intra-Abdominal Infections. Drugs

Secondary peritonitis

a. Perforated liver abscess b. Fibrin on small bowel loops.

(Image source: Clinic for Emergency Surgery, Clinical Center of Serbia, Belgrade, Serbia)

Secondary peritonitis

c. Colon perforation d. Infected pancreatic necrosis.

(Image source: Clinic for Emergency Surgery, Clinical Center of Serbia, Belgrade, Serbia)

Patient factorsAge, comorbidity, malnutrition1

Prolonged hospital length of stay2

Antimicrobial resistance1

Prior antibiotic exposureSeverity of illness1

Surgical factorsInadequate source control1

Ineffective antibiotic therapy3

Risk Factors for Treatment Failure

1.Mazuski JE, et al. Surg Infect. 2002;3:175-233.2.Barie PS, et al. Arch Surg. 1997;132:1294-1302. 3.Hopkins JA, et al. Am Surg. 1993;59:791-796.

Etiology

Lopez et al. World Journal of Emergency Surgery 2011Herzog , T., et al. 2010. Treatment of Complicated Intra-abdominal Infections In The Era of Multi-drug Resistant Bacteria. Eur J Med Res.

Clinical FeaturesAbdominal pain

Acute or insidious Initially, the pain may be dull and poorly localized (visceral

peritoneum) and often progresses to steady, severe, and more localized pain (parietal peritoneum).

SIRS manifestations: Core Body temperature > 38°C or < 36°C, heart rate > 90 beats per minute, respiratory rate > 20 breaths per minute (not ventilated) or

PaCO2 < 32 mm Hg (ventilated), WBC > 12,000, < 4,000 or > 10% immature forms (bands)

Hypotension and hypoperfusion signs such as lactic acidosis, oliguria, and acute alteration of mental status indicative of evolution to severe sepsis

Abdominal rigidity suggest peritonitis

Sartelli, Massimo. 2010. A focus on intra-abdominal infections. World Journal of Emergency Surgery

Diagnosis1. Microbiological : blood cultures, gram stain2. Radiological : Definitive diagnostic3. AXR4. USG5. CT

http://www.aic.cuhk.edu.hk/web8/Intra-abdo%20infection.htm

Rapid diagnosis1

Identification of high-risk patients1

Fluid resuscitation2

Empiric broad-spectrum antimicrobial therapy3

Source controlPercutaneous drainage2

Surgical intervention4

Management Principles in cIAI

1. Solomkin JS, et al. Clin Infect Dis. 2003;37:997-1005.2. Barie PS. J Chemother. 1999;11:464-477.3. Mazuski JE, et al. Surg Infect. 2002;3:175-233.4. Laroche M, et al. Eur J Clin Microbiol Infect Dis. 1998;17:542-550.

* Babinchak T, et al. Clin Infect Dis. 2005;41(suppl 5):S354-S367.* Mayne D, et al. Diagn Microbiol Infect Dis. 2012.

Doripenem has broad-spectrum activity against gram-positive, gram-negative, and anaerobic organisms

Doripenem’s in vitro activity is similar to that of imipenem and better than that of meropenem and ertapenem against gram-positive organisms

Doripenem is also more active against Pseudomonas aeruginosa and Burkbolderia cepacia

Doripenem

Chahine, Elias B. Doripenem: A new carbapenem antibiotic. 2010Jamieson, Conor. Doripenem. 2010. Clinical Farmacist.

Like other carbapenems, doripenem differs from most b-lactams by being very stable against hydrolysis by most b-lactamases, including ESBL and AmpC-producing Enterobacteriaceae

MOA : bactericidal inhibit cell wall synthesis by targeting the bacterial penicillin-binding proteins.

Doripenem

Doripenem in ASIA

Kurup, Asok. Antibiotic management of complicated intra-abdominal infections in adults: The Asian perspective. 2014. Elsevier

How to Optimize Antibiotic Treatment in Critically Ill Patient

High Impact

Doripenem is a new reliable antibiotics, comparable to meropenem in effectivity

With the increasing microbial resistency of meropenem, doripenem is a relialble alternative for eradicating infection.

Especially for pseudomonas infection, doripenem is superior than meropenem and tygacyclin..

Conclusion

• Doripenem 500 mgCOMPOSITION

• Complicated intra-abdominal infection

• Complicated urinary tract infections, including pyelonephritis

INDICATION

• cIaI : 500 mg/8 hr• cUTI : 500 mg/8 hrDOSAGE

• No teratogenic effect (Category B)

PREGNANCY & LACTATION

• 500 mg in single-use vialPACKAGING

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