Detailed , pain stakingly researched ppt on how to deal with sepsis in a primarily inflammatory disease condition

1. Antimicrobials
in
Acute Pancreatitis
Dr. Gowtham Krishna J
Consultant
Gem Hospitals
Chennai

2. A Brief history of sepsis
Sepo – I rot
Dangerous Decay
Rubor,calor,
dolor,tumor
function laesa

3. Sepsis is the
host's
inflammatory
response to
infection.
1.90% pts in ICU meet SIRS criteria
2.Is sepsis =SIRS+infection
Sepsis=infection??
all patients with sepsis have an
infection, the reverse is not
necessarily true
1.Host response is actually inherent
to the infection
2.this is an important component of
the difference between infection
and mere colonisation.
1.Sterile inflammation (present
in, for example, severe trauma,
burns, and pancreatitis) and
infection can both elicit similar
clinical signs of acute systemic
inflammation.
X
Tried to
introduce major
/minor criteria-
more of the
same

4. Are inflammation and Sepsis same then???
Vincent, J.-L., Opal, S. M., Marshall, J. C., & Tracey, K. J. (2013). Sepsis definitions: time
for change. The Lancet, 381(9868), 774–775. doi:10.1016/s0140-6736(12)61815-7
X X

5. Singer M, Deutschman CS, Seymour CW, et al. The Third International Consensus Definitions for Sepsis and
Septic Shock (Sepsis-3). JAMA. 2016;315(8):801–810. doi:10.1001/jama.2016.0287
 Sepsis differs from sterile inflammation, not by the
nature of the activated host response pathways or by
the types of organ dysfunction, but by the presence of
an underlying infectious process.

6. Dealing with
Sepsis/Inflammation
in an
acute inflammatory condition

7. The Mother of all ilustrations
1
2
3
Pancreatitis

8. (Preferential splanchnic)
ischemic environment also
induces mucosal atrophy, mitochondrial dysfunction,
oxidative stress, and cell death
Intestine remains the last organ to be
reperfused- (no evidence)
The
“How”
NO OF
SCORING
SYSTEM
CONSIDERS
TNF-a/Ca2+/
Adams DB, Cotton PB, Zyromski NJ, Windsor JA, editors. Pancreatitis: medical and surgical management. John Wiley & Sons; 2017 Apr 17.

9. “How” to classify Pancreatic sepsis
• 30-40%
• Impact of infection depends on the classification
• 3-4 th week of infection
Local
Infections
• >40%
• Whether relevance equal to that of a pancreatic
infection is questionable
Systemic
Infections

10. The “Which”-
The Pancreas: An Integrated Textbook of Basic Science, Medicine, and Surgery, Third Edition. Edited by Hans G. Beger, Andrew L. Warshaw,
Ralph H. Hruban, Markus W. Büchler, Markus M. Lerch, John P. Neoptolemos, Tooru Shimosegawa, and David C. Whitcomb.
SW Schmidt et all , 1999

11. The “When” to suspect the “what”
Bacteraemia-positive blood c/s sample-most of the cultured point to a gut
origin
Besselink MG, van Santvoort HC, Boermeester MA, Nieuwenhuijs VB, van Goor H, Dejong CH, Schaapherder AF, Gooszen HG. Timing and impact of infections in acute pancreatitis. Journal
of British Surgery. 2009 Mar;96(3):267-73.

12. Diagnosing sepsis-Battling an illusion or “are
we” – the case for “Procalcitonin”

13. Reinhart, K., Meisner, M., & Brunkhorst, F. M. (2006). Markers for Sepsis Diagnosis: What is Useful? Critical
Care Clinics, 22(3), 503–519. doi:10.1016/j.ccc.2006.03.003

14. Procap trial(1 ng/ml)-Siriwadana et
al 2022

15. Párniczky, A., Lantos, T., Tóth, E. M.,
Szakács, Z., Gódi, S., Hágendorn, R., … Mikó,
A. (2019). Antibiotic therapy in acute
pancreatitis: From global overuse to evidence
based recommendations.
Pancreatology. doi:10.1016/j.pan.2019.04.003
Jaber S, Garnier M, Asehnoune K, Bounes F, Buscail L, Chevaux JB, Dahyot-Fizelier C,
Darrivere L, Jabaudon M, Joannes-Boyau O, Launey Y. Guidelines for the management of
patients with severe acute pancreatitis, 2021. Anaesthesia Critical Care & Pain Medicine. 2022
Jun 1;41(3):101060.

16. Antibiotics- Battling a deeply camouflaged
enemy

17. The Septic diversity of pancreatic infections…
1986
1989
1992
1993
2000
2001
2002
2013
: N.G. Mowbray et al., The microbiology of infected pancreatic necrosis, Hepatobiliary & Pancreatic
Diseases International (2018), https://doi.org/10.1016/j.hbpd.2018.08.007
Vaishnavi C, Bush N, Kochhar R. Infections in Acute Pancreatitis: A
Review. J Gastrointest Infect. 2019 Jan;9(1):28-37.

18. SW Schmidt et all , 1999
Frequency of bacteria(FB)/PIS-percentage of
inhibited strains
Büchler, M., Malfertheiner, P., Frieβ, H., Isenmann, R., Vanek, E.,
Grimm, H., … Beger, H. G. (1992). Human pancreatic tissue concentration
of bactericidal antibiotics. Gastroenterology, 103(6), 1902–
1908. doi:10.1016/0016-5085(92)91450-i

19. • Aminoglycosides-poor penetration of pancreas if given intravenously in the dosages recommended by the
manufacturer. –Less EF even 120 min after administration
• Acylureidopenicillins and third-generation cephalosporins consisting of mezlocillin, piperacillin, ceftizoxime, and
cefotaxime had adequate pancreatic tissue concentrations and acceptable pancreatic-to-serum ratios (Intermediate
EFs)Always combine with drugs used to treat anaerobes and/or gram-positive bacteria.
• Adequate tissue concentrations and good (imipenem) or high (ciprofloxacin, ofloxacin) tissue-to-serum ratios acheived.
Because of their broad-spectrum bactericidal activity against gram-negative and gram-positive germs (ciprofloxatin,
ofloxacin, imipenem) and against anaerobes (imipenem), these drugs were judged as having high EFs of 0.86-0.98.
• Metronidazole, a compound with a bactericidal spectrum almost exclusively against anaerobes, showed good
penetration into the pancreas and a high tissue-to-serum ratio-(Must include in regimens to support anaerobic
coverage)
Büchler, M., Malfertheiner, P., Frieβ, H., Isenmann, R., Vanek, E., Grimm, H., … Beger, H. G. (1992). Human pancreatic tissue concentration of bactericidal
antibiotics. Gastroenterology, 103(6), 1902–1908. doi:10.1016/0016-5085(92)91450-i
D.R.J. Wolbrink et al. Management of infected pancreatic necrosis in the intensive care unit:a narrative review. Clinical Microbiology and Infection 2019
Selection of the weapon

20. D.R.J. Wolbrink et al. Management of infected pancreatic necrosis in the intensive care unit:a narrative review.
Clinical Microbiology and Infection 2019
A Candida Colonization Index Score (CCIS) was calculated for each patient using the methods described
[8] as follows: CCIS = ratio of the number of non-blood distinct body sites colonised with Candida spp to
the total number of body sites cultured. A CCIS ≥ 0.5 predicts Candida infection; therefore, patients who
had ICI and a CCIS ≥ 0.5 were defined as true positives.

21. Sr.PCT raise
D.R.J. Wolbrink et al. / Clinical Microbiology and
Infection 2019
Our antibiotic protocol

22. • It involves a carbapenem in case of suspicion of sepsis(Preferred-Meropenam)
• Antifungal – If duration of disease is more/multiple hospital admissions/previous antibiotic
administartions- (Preferred Azole antifungal-Flucanozole(candida)
Occhionorelli S, Morganti L, Cultrera R, Andreotti D, Maccatrozzo S, Cappellari L, Stano R, Vasquez G. Acute necrotizing pancreatitis: can
tigecycline be included in a therapeutic strategy?. Il Giornale di chirurgia. 2015 Jan;36(1):15.
Occhionorelli et
al.2015(Italy)
How we win our wars

23. De-escalation –Duration of therapy
Empirical/
suspicion of sepsis
Targeted
(FNA or Culture positive)
Clinical
decison
D.R.J. Wolbrink et al. Management of infected pancreatic necrosis in the intensive care unit:a
narrative review. Clinical Microbiology and Infection 2019

24. Summary
1. Routine use of prophylactic antibiotics in patients with severe AP or sterile necrosis is not
recommended.
2. However antibiotics should be given for any extrapancreatic infection, such as cholangitis,
catheter-acquired infections, bacteremia, urinary tract infections, pneumonia
3. Infected necrosis should be considered in patients with pancreatic/extrapancreatic necrosis
who deteriorate or fail to improve after 7 – 10 days of hospitalization.

25. • In patients with infected necrosis, antibiotics known to penetrate pancreatic necrosis, can
delay or avoid intervention, thus decreasing morbidity and mortality
• Routine administration of antifungal agents along with prophylactic or therapeutic
antibiotics is not recommended.
• Probiotics and selective digestive decontamination are not recommended.(PROPATRIA
trial.)

26. The newer developments
Diagnosing Sepsis
• CD 64 index
• Shapiro PCT A(Algorithm)

29. Primed neutrophils and other
intestine derived toxic factors
were the mediators of
MODS.(were transported by
thoracic duct lymph)
increased gut permeability but
independent of bacterial
translocation
Lung injury mediated by hemorrhagic
shock‐conditioned mesenteric lymph was key
to validating this concept in the experimental
setting.(mesenteric lymph vs portal vein
plasma)
Deitch EA. Gut‐origin sepsis:
evolution of a concept.
Surgeon 2012;10(6):350–356.
(75% from abdomen and
pelvis)
(Discuss
ligation vs
drainage)

30. Schuetz P, Beishuizen A, Broyles M, Ferrer R, Gavazzi G, Gluck E, González del Castillo J, Jensen J, Kanizsai P, Kwa A, Krueger S, Luyt C, Oppert M, Plebani
M, Shlyapnikov S, Toccafondi G, Townsend J, Welte T, Saeed K. Procalcitonin (PCT)-guided antibiotic stewardship: an international experts consensus on
optimized clinical use. Clinical Chemistry and Laboratory Medicine (CCLM). 2019;57(9): 1308-1318. https://doi.org/10.1515/cclm-2018-1181

31. The idea of a pancreatic infection
• Intestine drives critical illness-1960’s-bacterial endotoxin demonstrated -
Bacterial Translocation Hypothesis-1960s
• Gut Motor Hypothesis – 1980’s (changes in intestinal flora-increased gut
permebility-pathogens enter through portal circulation-discredited)
• Neutrophil priming-local gut & distant organ injury(Second hit hypothesis)-
exposure to mesenteric circulation (ischemia-reperfusion injury)
• Gut lymph hypothesis-ischemic gut/bypass portal circulation/end organ
damage
The Pancreas: An Integrated Textbook of Basic Science, Medicine, and Surgery, Third Edition. Edited by Hans G. Beger, Andrew L. Warshaw,
Ralph H. Hruban, Markus W. Büchler, Markus M. Lerch, John P. Neoptolemos, Tooru Shimosegawa, and David C. Whitcomb.

32.  Sepsis differs from sterile inflammation, not by the nature of the activated host response pathways
or by the types of organ dysfunction, but by the presence of an underlying infectious process.
 The first diagnostic priority in managing a patient with sepsis is, therefore, to identify any focus of
invasive infection.
 Clinical phenotype is at least partly shaped by the infecting organism.