PowerPoint PresentationDr Sarah Wong Infectious Diseases Advanced Trainee Austin Health 2015
Mr JB
acute left iliac fossa pain,
vomiting,
Past History
2. Open appendicectomy
Recent hospital admission 4 days prior – no clear diagnosis on discharge
Presented with colicky diffuse abdominal pain and vomiting. No diarrhoea.
WCC 13.8/ Neut 12 ,CRP 3.4 , lipase 12
CT AP: epiploic appendagitis adjacent to
recto sigmoid junction
duo forte
24 -36 hours of abdominal pain
Multiple episodes of bloody diarrhoea.
Clinical Examination
RR 22
Bloody diarrhoea with mucous noted in ED
Laboratory investigations- Day 1
Na 140 /4.1/96/ Ur 4.7/Cr96/eGFR 78
LFT normal
CRP 3.5
Lipase 19
CT Abdomen Pelvis Day 2 CT AP 5 days earlier
CT Abdomen Pelvis Day 2
Presumed infective colitis/ C. difficile colitis IV ceftriaxone, oral metronidazole
Faecal Specimen – Day 2
Clostridium Toxin gene assay by PCR Toxin B not detected
Enteric Bacterial PCR panel Salmonella spp. - Shigella spp./ Enteroinvasive E coli - Campylobacter jejuni/coli - Shiga toxin 1 & 2 (Shiga producing E coli or Shigella dysenteriae) -
Faecal specimen
Macroscopic description Loose Loose
Leucocytes + Erythrocytes not seen
Enteric Bacterial PCR panel
ID Consult Day 3
Non infective colitis
Could this be Antibiotic associated haemorrhagic colitis w Klebsiella oxytoca ?
Antibiotic Associated Diarrhoea
Enterotoxigenic Clostridium perfringens 12
Salmonellosis 13,14
1. Mandell et al., 2010 2. Levine et al., 1995 CID 13. Neal et al., 1994 BMJ 14. Olsen et al., 2001 NEJM 12. Asha et al., 2002 JMM
Antibiotic Associated Haemorrhagic Colitis
AAHC with Ko
Specific clinical, endoscopic, histopathological and microbiological characteristics 3,4,5
3. Hogenauer et al., 2008 Emerging Infections 4. Hogenauer et al., 2006 NEJM 5. Miller et al., 1998 J Gastro. Hep
Klebsiella oxytoca
Detected in intestines of 2-10% of healthy subjects 11
AAHC is associated with antibiotic driven enterobacterial overgrowth 12
Antibiotic clearance of a niche in the colon facilitates growth of K oxytoca ( 10 7 CFU/g faeces in acute AAHC vs 102 CFU/g in healthy subjects ) 12
Specific Ko strains have cytotoxic effects on human epithelial cells 12
11. Zollner-Schwetz et al., 2008 CID 12. Schneditz et al., 2014 PNSA
Attempts to prove association Author/ Year Content No. w
AAHC/(%) Positive for Klebsiella Oxytoca
Sakurai 1979 (Japan)
N=56 acute colitis 8 patients with bloody diarrhoea post ampicillin
- 3/8 patients
Beaugerie 2003 (France)
N=93 acute colitis (colonic bxp) 12 patients had C. difficile, non HC 4 patients had AAHC (2 Salmonella)
4 (4%) 2/4 patients
Hogenauer 2006 (Graz, Austria)
6 (5%) 5/6 patients
Zollner-Schwetz 2008 (Graz, Austria)
3 (3%) 3/3 patients
Study period 2001-2004 (38 months)
Setting Tertiary hospital Austria 10,000 admissions /yr
Ko prevalence 1.6% (6/385 healthy subjects)
Diagnosis of infectious diarrhoea
74 cases Salmonella 54 cases campylobacter 2 cases Shigella 121 cases of C. difficile 0 cases of Yersinia/ EHEC
Diagnosis of AAHC Ko 5/22 consecutive patients with suspected AAC - Positive culture for Ko - Negative for C difficile
Klebsiella oxytoca as a Causative Organism of Antibiotic-Associated Haemorrhagic Colitis Hogenauer et al., 2006 NEJM
70 Female Sprague- Dawley rats
Ko + Aug DF
NSAID
Ko + Aug DF was associated with right sided haemorrhagic colitis
Ko + Aug DF
Ko+ Aug DF+NSAID
Morphologic change in caecum of rats 1. Mucosal inflammation 2. Epithelial alteration 3. Mucosal haemorrhage 4. Erosion (more severe in
rats given indomethacin)
Clinical presentation AAHC Clostridium difficile AAC 8
Antibiotic exposure to Sx 2- 7 days Risk factor : NSAID use 3
5 days to 10 weeks (longer)
Symptoms Severe abdominal cramps 3,6 Bloody diarrhoea 3,6
Fever Abdominal pain and cramping Watery profuse diarrhoea occult colonic bleeding
Laboratory investigations Mild Leucocytosis3,6 Leucocytosis
Toxin mediated Cytotoxin 3,6 Toxin B, Toxin A, Binary Toxin
Colonoscopy Mucosal haemorrhage and oedema 7
Segmental distribution R side– ascending colon and caecum3
Non Specific Pseudomembranous colitis: Adherent
inflammatory membrane (pseudomembrane) overlying sites of mucosal injury
Histology Coagulative necrosis of surface epithelium Crypts with focal ulceration and fibrin deposition Microvascular fibrin thrombus formation Vascular engorgement Subepithelial erythrocytes 7
surface erosion of the superficial colonic crypts LP adjoining necrosis has infiltrate of neutrophils and eosinophils Plaque like pseudomembrane of neutrophils, fibrin, cellular debris over mucosal surface
)
3. Hogenauer 2008 Emerging Infections
1. Mandell et al., 2010 3. Hogenauer et al., 2008 Emerging Infections
Clinical presentation AAHC Clostridium difficile AAC
Potential Complications Minimal Toxic mega colon, intestinal perforation, death
Duration of Illness Spontaneous resolution within days once antibiotic stopped
Brief OR profuse diarrhoea over 7- 14 days
Approach to treatment Withdraw antibiotics Withdraw antibiotics Add antibiotics
(Green, Tran and Janda, 2009)
6. Green et al., 2009 CMN
Cytotoxins associated with AAHC
9. Joainig et al., 2010 jCM
University of Graz subtypes of KO produce cytotoxin AAHC 04/1 0 – clinical isolate from AAHC patient ATCC 13182 – laboratory strain of KO
Growth Curve
TO X
IN E
FF EC
Missed alternative pathology
Limitations of C. difficile testing
Presence of genetic cluster supports but does not prove cytotoxin production resulting in AAHC
Did Mr JB have AAHC with Ko?
symptoms of bloody diarrhoea
Significant growth of K oxytoca in the stool culture
The patient’s rapid clinical response when Augmentin duo forte therapy was discontinued
Presence of genetic cluster supports possibility of cytotoxin production resulting in AAHC
Consideration in the Laboratory
Unformed stool specimen
BOTH C difficile toxin and enteric PCR negative with WCC ≥ 2
Discuss with Medical Micro ? Need for Further Bacterial Culture
Clinically consistent presentation
Considerations on the ward-future project
Radiology audit of patients over last 12-18 months with CT evidence of colitis, found not to have Clostridium difficile infection or ischaemia Denominator for potential AAHC cases
Acknowledgements
Austin Health Laboratory Staff