Acute pancreatitis and infective complications

Publication: 22/10/2021  --
Last review: 01/01/1900  
Next review: 22/10/2024  
Clinical Guideline
CURRENT 
ID: 7210 
Approved By: Improving Antimicrobial Prescribing Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2021  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

ACUTE PANCREATITIS & INFECTIVE COMPLICATIONS

Acute pancreatitis must be graded for severity

Mild

Absence of organ failure and local/systemic complications

Moderately severe

Transient organ failure or local/systemic complications in the absence of persistent organ failure

Severe

Persistent organ failure.  Almost inevitably coinciding with local complications

Acute pancreatitis is diagnosed if 2 of the following 3 features are present

  • Symptoms of acute pancreatitis (severe, persistent epigastric pain, often radiating to the back)
  • Amylase level >330
  • CT evidence of pancreatitis

DIAGNOSTICS

For patients with a presumed diagnosis of acute pancreatitis the following diagnostic tests should be taken to confirm diagnosis:

All patients

Serum Amylase

CT scan of the abdomen to look for evidence of pancreatitis (if the diagnosis is in doubt - see diagnostic criteria above)

Assess for underlying cause of Pancreatitis

Assess for concurrent infections, e.g. cholecystitis. If found treat as per the relevant guideline

Moderately severe pancreatitis (Transient organ failure <48 hrs and/or local complications)
Severe pancreatitis
(Persistent organ failure >48hrs)

Repeat CT at 7 days

Severe pancreatitis with signs of sepsis (pyrexia, SIRS response, raised inflammatory markers4)

Blood cultures before antibiotics.   Paired set if long line in situ.

Assess for other sources of sepsis (e.g. chest, urinary tract, skin/soft tissue) and send relevant microbiological samples: sputum, MSU/CSU, wound swabs etc

For the full management pathway for acute pancreatitis see appendix 1

INFECTED NECROTIC PANCREATITIS (INP)

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DIAGNOSTICS

Once INP has been identified the following should be done

All patients

Blood cultures before antibiotics

Inflammatory marker monitoring (CRP, WCC) to assess trends in the context of the overall clinical picture4.

Matured INP (walled off)

Pus/fluid samples from radiological, endoscopic or surgical drainage procedures to be sent to MC&S

Empirical antifungal agents being started (on discussion with Microbiology)

Beta-D-Glucan

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EMPIRICAL TREATMENT

Pancreatitis, in and of itself, is not an indication for antimicrobial treatment, nor prophylaxis.  However, infective complications can occur at a late stage in severe pancreatitis and when there is evidence of infected necrotic pancreatitis (positive microbial cultures or gas evident in the necrotic collection on CT), antimicrobial treatment becomes an important part of management both whilst awaiting the wall to mature (to allow intervention) and subsequently until the source is adequately under control.

Empirical options for Pancreatitis

Previous Microbiology results MUST be reviewed for carriage of resistant organisms (e.g. ESBLs, AMP-C, CPE, VRE, MRSA).  The following empirical options may not be appropriate and Microbiology should be contacted for an appropriate alternative.

Mild Pancreatitis

Antibiotics NOT recommended

If concomitant cholangitis or other extra-pancreatic infection this should be treated as per the relevant guideline.

Prophylaxis in moderately severe or severe pancreatitis

Antibiotics NOT recommended

If concomitant extra-pancreatic infection this should be treated as per the relevant guideline.

 

Recommended (1st line) treatment

2nd line treatment

Notes and Duration

Where IV antibiotics are indicated blood cultures should be sent before initiating treatment.

Infected necrotic pancreatitis

<65 years old:
Cefuroxime electronic Medicines Compendium information on Cefuroxime 1.5g 8-hourly IV
PLUS
Metronidazole electronic Medicines Compendium information on Metronidazole 500mg 8-hourly IV

>65 years old or CDI risk
Piperacillin/tazobactam electronic Medicines Compendium information on Piperacillin/tazobactam 4.5g 8-hourly IV

Allergy to penicillin or cephalosporins

Linezolid1 600mg 12-hourly IV PLUS
Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin 400mg 12-hourly IV
PLUS
Metronidazole electronic Medicines Compendium information on Metronidazole 500mg 8-hourly IV

Where Linezolid is contra-indicated, use Teicoplanin IV 12mg/kg (see prescribing guidance) in its place

(If there is adequate enteral absorption consider oral antibiotics:
Linezolid1 600mg 12-hourly PO
PLUS
Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin 500 mg 12-hourly PO
PLUS
Metronidazole electronic Medicines Compendium information on Metronidazole 400 mg 8-hourly PO)

Antibiotics should be reviewed with any culture results when they are available.  If not weekly review is needed.

 

There is no standard duration of antibiotics for this condition as the individual course of the disease must be taken into account, including clinical response, WCC and CRP trends and imaging.  Please discuss with Microbiology on a case by case basis.

 

Infected necrotic pancreatitis not responding to antibiotics3:

Anidulafungin electronic Medicines Compendium information on Anidulafungin 200mg once daily IV for one day, then 100mg once daily IV thereafter

This is a restricted antimicrobial and should only be initiated on discussion with Microbiology, and must be reviewed at 72 hours with clinical response and B-D-Glucan result.

Patients not responding to antibiotics should be discussed with an infection specialist

Prophylactic antifungals are not recommended3.

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REVIEW BY 72

By 72 hours of antimicrobial treatment, diagnostics should have proven your initial diagnosis or guided to a new diagnosis.

If your patient in on IV treatment this should be reviewed daily.

The review, outcome and future plans (where appropriate) should be documented in the medical notes.

If the diagnosis is still correct your options are now:

IVOS

Due to the nature of INP the course of IV antibiotics is normally prolonged and switch to oral agents will normally be directed rather than empirical and should be discussed with Microbiology.

Stop

If no signs of infection and diagnostics support this decision.

Change

If the patient is not clinically responding, check any culture results and discuss treatment options with Microbiology.

Continue

If the patient is improving but does not fully meet ACED criteria. Review daily until ready to switch. Document the reason for continuing.

On-going review of antibiotics (see appendix 2 for flowchart of this process)

Due to the nature of necrotic pancreatic collections, single drainage procedures rarely produce adequate source control and repeated intervention is required, and prolonged courses of antibiotics are often required.  Due to needing to wait for wall maturation, sampling of the collection is normally not possible prior to the initiation of antibiotics.

Once antibiotics have been established and the patient clinically responding, they should be reviewed regularly until intervention is possible.  Repeat imaging, inflammatory markers and clinical observations are integral to these reviews4.

If the patient deteriorates clinically, they should be discussed with Microbiology regarding changes to the antimicrobials (antibiotics +/- antifungals), which should take into account any culture results available and the latest imaging and drainage procedure possibilities.

Once source control is achieved, antimicrobials can be stopped.  4 days of antibiotics following source control is adequate.

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DIRECTED THERAPY

This is should be discussed on a case-by-case basis with Microbiology.

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FOOTNOTES

  1. Please note - linezolid is only licensed for 4 weeks.  Please discuss with Microbiology if this is considered.
  2. Antimicrobials in Pancreatitis
    There is limited pharmacodynamic and pharmacokinetic evidence available for the penetration of drugs into necrotic pancreatic collections.  The pancreas itself has a blood-pancreas-barrier that means not all antimicrobials gain access to the parenchyma of the pancreas in adequate concentrations.  Most studies have been undertaken on normal pancreatic tissue.  However, it is known that inflammation disrupts normal physiological barriers and adequate penetration of the following drugs has been demonstrated, or can assumed based on clinical data outcomes: piperacillin-tazobactam, meropenem (and imipenem), fluoroquinolones and cephalosporins. Where fungal infection is evidenced or suspected then fluconazole (where susceptible organisms) or anidulafungin have been used.
  3. Empirical antifungal treatment should be considered when there is a failure to improve on broad spectrum antibiotics (and/or with drainage), and should always be discussed with an infection specialist.  Patients with infected necrotic pancreatitis can have a number of risk factors for invasive fungal disease (broad spectrum antibiotic exposure, multiple indwelling catheters, parenteral nutrition, prolonged hospitalisation) and therefore empiric antifungal treatment may be indicated.  Samples from drainage procedures, along with blood cultures should be sent prior to any antimicrobial change for lack of response, with a B-D-Glucan sent on starting anti-fungal agents empirically.  If it is negative, they should be reviewed and stopped (if clinical response to antifungal has been noted, please discuss with Microbiology first).  Fungi should always been treated if they are found on culture results from pancreatic collection samples.
  4. A note on inflammatory marker monitoring: there were no specific cut-offs for white cell count and CRP within the context of infected necrotic pancreatitis as both markers will be raised in both sterile and infected necrosis. As such it is not possible to give definitive cut-offs to guide the initiation and cessation of antibiotics. However, these markers should be monitored so that trends can be demonstrated, that can be utilised in conjunction with the broader clinical picture by the specialist pancreatologist, and in conjunction with an infection specialist, to guide antimicrobial therapy. Procalcitonin is a more specific infection marker. It is used by intensivists to guide the use of antibiotics in critically ill patients. It may be useful in guiding antibiotic use in severe pancreatitis, although this is yet to be definitively demonstrated. Its use in severe pancreatitis is being investigated in the PROCAP trial and we will hopefully be able to be used as a more definitive marker in future iterations of this guidance.

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APPENDIX 1

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APPENDIX 2

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APPENDIX 3: LOCAL AUDIT EVIDENCE

A recent retrospective audit (2017/18) of 20 patients with infected necrotic pancreatitis was undertaken.  This audit showed the following:

  • 19 patients underwent drainage (14 radiological, 3 endoscopic and 2 laparoscopic)
  • Samples were sent from 79% of procedures; 80% of these samples impacted the antimicrobial treatment plan.
  • 33 micro-organisms were isolated from first drainage samples (table 1)
  • 95% of patients had more than 1 drainage procedure, with more than half having 2 or more additional procedures.  Repeat samples were sent in 61%.
  • In total 42 isolates were reviewed as part of the audit, with higher rates of resistance seen with later samples (table 2).

Table 1: Organisms isolated from first drainage procedures

Organism

Number of isolates

Enterobacterales
  E coli
  Citrobacter koseri
  Klebsiella pneumoniae
  Hafnia alvei


3
1
1
1

“Coliforms” (not further ID’s)

8

Unidentified gram negative bacillus

1

Pseudomonas spp

1

Enterococcus faecium

5

Enterococcus faecalis

1

Streptococcus constellatus

2

Coagulase negative staphylococci

1

MRSA

1

Anaerobes

4

Yeasts
   Candida albicans
   Candida lusitaniae


1
1

Table 2: Resistance profiles of isolates

Antibiotic

% resistance from initial sampling isolates

% resistance from all sampling isolates

Co-amoxiclav electronic Medicines Compendium information on Co-amoxiclav

31% (7 of 22)

39% (11 of 28)

Cefuroxime electronic Medicines Compendium information on Cefuroxime

22% (4 of 22)

42% (11 of 26)

Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin

19% (3 of 16)

36% (9 of 25, with 8 testing fully resistant and 1 testing intermediate)

The changing profile of resistance is likely to represent changes in the enteric flora of the patient following exposure to antibiotics, and, where a patient is not responding to the antimicrobials that are in use, can be used to help guide any changes that are required. 

Provenance

Record: 7210
Objective:
Clinical condition:

Acute pancreatitis and infective complications

Target patient group:
Target professional group(s): Pharmacists
Secondary Care Doctors
Adapted from:

Evidence base

  • Yadav D, Lowenfels AB. The epidemiology of pancreatitis and pancreatic cancer. Gastroenterology. 2013;144(6):1252-61.
  • Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, et al. Classification of acute pancreatitis--2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62(1):102-11.
  • O'Reilly DA, McPherson SJ, Sinclair MT, Kelly K, Ellis D, Mahoney N, et al. Treat the cause: A review of the quality of care provided to patients treated for acute pancreatitis. NCEPOD; 2016.
  • Crockett SD, Wani S, Gardner TB, Falck-Ytter Y, Barkun AN, American Gastroenterological Association Institute Clinical Guidelines C. American Gastroenterological Association Institute Guideline on Initial Management of Acute Pancreatitis. Gastroenterology. 2018;154(4):1096-101.
  • de Vries AC, Besselink MG, Buskens E, Ridwan BU, Schipper M, van Erpecum KJ, et al. Randomized controlled trials of antibiotic prophylaxis in severe acute pancreatitis: relationship between methodological quality and outcome. Pancreatology. 2007;7(5-6):531-8.
  • Villatoro E, Mulla M, Larvin M. Antibiotic therapy for prophylaxis against infection of pancreatic necrosis in acute pancreatitis. Cochrane Database Syst Rev. 2010(5):CD002941.
  • Working Party of the British Society of G, Association of Surgeons of Great B, Ireland, Pancreatic Society of Great B, Ireland, Association of Upper GISoGB, et al. UK guidelines for the management of acute pancreatitis. Gut. 2005;54 Suppl 3:iii1-9.
  • Charnley R, Horton A, Lucas A, Rasheed A, Baranidharan G, Booth J, et al. Pancreatitis. NICE; 2018.
  • Tang BM, Eslick GD, Craig JC, McLean AS. Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. Lancet Infect Dis. 2007;7(3):210-7.
  • Bouadma L, Luyt CE, Tubach F, Cracco C, Alvarez A, Schwebel C, et al. Use of procalcitonin to reduce patients' exposure to antibiotics in intensive care units (PRORATA trial): a multicentre randomised controlled trial. Lancet. 2010;375(9713):463-74.
  • Rau BM, Kemppainen EA, Gumbs AA, Buchler MW, Wegscheider K, Bassi C, et al. Early assessment of pancreatic infections and overall prognosis in severe acute pancreatitis by procalcitonin (PCT): a prospective international multicenter study. Ann Surg. 2007;245(5):745-54.
  • Greenberg JA, Hsu J, Bawazeer M, Marshall J, Friedrich JO, Nathens A, et al. Clinical practice guideline: management of acute pancreatitis. Can J Surg. 2016;59(2):128-40.
  • Working Group IAPAPAAPG. IAP/APA evidence-based guidelines for the management of acute pancreatitis. Pancreatology. 2013;13(4 Suppl 2):e1-15.
  • Solomkin JS. Evaluating evidence and grading recommendations: the SIS/IDSA guidelines for the treatment of complicated intra-abdominal infections. Surg Infect (Larchmt). 2010;11(3):269-74.
  • De Waele JJ. Rational use of antimicrobials in patients with severe acute pancreatitis. Semin Respir Crit Care Med. 2011;32(2):174-80.
  • Grayson ML, Cosgrove SE, Crowe S, Hope W, McCarthy JS, Mills J, et al. Kucers' The Use of Antibiotics: A Clinical Review of Antibacterial, Antifungal, Antiparasitic, and Antiviral Drugs. 7th ed: CRC Press; 2017.
  • Local Audit evidence (see appendix 3, after authors)

Approved By

Improving Antimicrobial Prescribing Group

Document history

LHP version 1.0

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