S_c7

Severe acute pancreatitis

Academy for Infection Management 2006 (All Rights Reserved)

History
33-year-old male Alcohol binge: vodka Awake and conversant Severe abdominal pain, vomiting, dyspnoea

Physical and laboratory examinations

Temperature 38.1C Pulse 96 bpm, respirations 20/min Blood pressure 110/70 mmHg Abdomen tender, distended, quiet Amylase 3500 IU/L Lipase 1100 IU/L AST >250 IU/L LDH >350 IU/L WBC count 16 000/mm3 Arterial blood gases:
pH 7.30, PaCO2 32, PaO2 58, BE -5

Which evaluations would you perform to determine if the patient has severe pancreatitis? 1. C-reactive protein 2. Computed tomography (CT) scan 3. Severity scores
a. b. c. d. Ranson score Glasgow (Imrie) score APACHE II or III score Balthazar score

Initial tests and treatment

Fluid resuscitation Chest radiography CT Calculation of Ranson score (at 48 hours)

The patient has severe pancreatitis by CT criteria

Central necrosis of the pancreas >30% Peripancreatic oedema and inflammation

Ranson score: a pancreatitisspecific severity of illness score

Present on admission Age >55 years WBC >16 000/mm3 Glucose >200 mg/dL LDH >350 IU/L AST >250 IU/L During the first 48 hours Haematocrit decrease >10% points BUN increase >5 mg/dL Serum calcium <8 mg/dL PaO2 <60 mm Hg Base deficit <-4 mEq/L Fluid sequestration >6 L

The patient has eight positive Ranson criteria

SGOT >250 IU/L LDH >350 IU/L WBC count >16 000/m m3 PaO2 <60 mm Hg Base deficit <-4 mEq/L Net fluid sequestration >6 L Calcium concentration <8 mg/dL Haematocrit decrease >0 percentage points
100 90 80

Mortality (%)

70 60 50 40 30 20 10 0 12 34 56 78 >8

Rans on s core

The predicted mortality rate for a Ranson score of 8 is 60%

Eachempati et al. Arch Surg 2002

Figure reproduced with permission from Arch Surg

Would you start prophylactic antibiotics?

1. No 2. Yes, with
a. b. c. d. e. Ceftriaxone? Gentamicin plus metronidazole? Imipenem/cilastatin or meropenem? Ciprofloxacin plus metronidazole? Other?

3. Yes, plus fluconazole

Penetration of pancreatic tissue and pancreatic juice by antimicrobial agents

Poor
Aminoglycosides Vancomycin

Variable
Penicillins Cephalosporins

Good
Carbapenems Metronidazole Quinolones Fluconazole
Bassi et al. Antimicrob Agents Chemother 1994;38:830836

What is this patients risk of developing infection?

1. 2. 3. 4. <10% 10%30% 30%50% >50%

Incidence of peripancreatic infection after acute pancreatitis

All episodes Any pancreatic necrosis Pancreatic necrosis >30% Pancreatic necrosis >50% 3%7% 20%70% 15%30% 40%70%

Beger et al. Gastroenterology 1986;91:433438 Beger et al. Pancreatology 2003;3:93101 Buchler et al. Ann Surg 2000;232:619625

Pancreatic infections almost never occur before Day 7

The peak incidence is at Day 14
Should prophylaxis be given? for the entire at-risk period?

68% of data

95% of data

99% of data

Day 7

Day 14

Day 21
Beger et al. Gastroenterology 1986;91:433438

How long would you administer antibiotic prophylaxis?

Should prophylaxis be administered for the entire risk period? 1. 2. 3. 4. 5. Would not administer prophylaxis 1 week 2 weeks 3 weeks Until ICU discharge

Prophylactic antibiotics for severe acute pancreatitis

First double-blind, placebo-controlled trial

114 patients enrolled, 76 with necrosis Entry criteria

C-reactive protein >150, or Necrosis on contrast-enhanced CT, and <72 hours from onset of pain

Ciprofloxacin plus metronidazole vs placebo All patients treated 1421 days unless converted to open-label (therapeutic) use
Isenmann et al. Gastroenterology 2004;126:997

Results: intention-to-treat analysis (n=114)

Ciprofloxacin/ metronidazole Infected necrosis (%) Extra-pancreatic infection (%) Mortality (%) Need for operation (%) 12 22 5 17 Placebo 9 23 7 11

Prophylactic antibiotics for severe acute pancreatitis: double-blind, placebo-controlled trial

100 patients with severe acute pancreatitis

Contrast-enhanced CT
multiple peripancreatic fluid collections by non-contrast CT, plus C-reactive protein >120 mg/dL, or

Multiple organ dysfunction score >2 points Meropenem 1 g q8h vs placebo Primary end-point
Pancreatic/peripancreatic infection within 42 days
Dellinger et al. Ann Surg (in press)

Prophylactic antibiotics for severe acute pancreatitis: trial results

Meropenem % 18 26 20 Placebo % 12 20 18 pvalue 0.41 0.48 0.80

Outcome Pancreatic/peri pancreatic infection Surgical intervention Mortality

Dellinger et al. Ann Surg (in press)

The downside of prolonged antibiotic prophylaxis

Allergy Expense Resistance Superinfection

Prophylactic antibiotics for severe acute pancreatitis

Recovery of resistant bacteria
90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Antibiotic group Placebo group Isenmann et al. Gastroenterology 2004;126:997

p<0.0001

What antibiotic regimen was prescribed initially?

This patient was NOT started on antibiotic prophylaxis

The patients condition improves

Resolution of leukocytosis Resolution of pain Oral intake resumed

The patient develops multiple organ dysfunction syndrome

Day 16 New fever and leukocytosis Increased abdominal distention ARDS
Low VT ventilation PEEP

Renal dysfunction What do you do now?

Repeat CT scan shows a large peripancreatic fluid collection

Small amount of still-perfused pancreas

What action(s) should be taken now?

1. 2. 3. 4. Continue to observe Microbiological sampling Repeat CT scan with fine-needle aspiration Operate

What specimen(s) would you collect?

1. 2. 3. 4. None Blood Sputum Peripancreatic fluid (fine-needle aspiration)

Incidence of infected pancreatitis when sought by fine-needle aspiration

All Sensitivity (%) Specificity (%) Pos. pred. value (%) 88 90 83 > Week 1 97 100 100

Neg. pred. value (%)

Accuracy (%)

93
89

98
98

Results of culture and susceptibility testing

Patient underwent CT-guided fine-needle aspiration
Peripancreatic fluid
Proteus mirabilis (pan-sensitive)

Blood
No growth

Urine
No growth

Sputum
No growth

Microbiology of infected pancreatic necrosis (%)

Fernandez-del Castillo 1998 Gram-positive 55 Buchler 2000 46

Gram-negative
Anaerobes Candida spp. Mixed

26
2 17 Not reported

36
4 6 10

Fernandez-del Castillo et al. Ann Surg 1998;228:676684 Buchler et al. Ann Surg 2000;232:619626

Therapy
Formal operative debridement and drainage Only one operation required Meropenem x 14 days Choice based on tissue penetration Dosage reduction for creatinine clearance 35 mL/min

Outcome
Fever and leukocytosis resolve Organ dysfunction resolves Renal function improves
Creatinine stabilises at ~2.0 mg/dL

Patient recovers

Key learning points

1. Most patients (~85%) with acute pancreatitis do not develop severe disease 2. Determination of severity of illness provides prognostic information and can guide therapy 3. Antimicrobial prophylaxis does not prevent secondary infection in severe acute pancreatitis, but does increase risk of resistant pathogens if infection does occur 4. Antibiotics may be withheld until needed for therapy

AIM core principles

Select the most appropriate antibiotic depending on the patient, risk factors, suspected infection and resistance Recognise that prior antimicrobial administration is a risk factor for the presence of resistant pathogens Ensure adequate containment of the infection source by removing contaminated devices and draining/debriding infectious tissue