Intra-Abdominal Candidiasis, Candida peritonitis Paschalis Vergidis, MD, MSc Infectious Diseases Consultant Manchester University NHS Foundation Trust

Learning Objectives To understand the different forms of intra-abdominal candidiasis To discuss the risk factors for intra-abdominal candidiasis To review the management and outcomes of intra-abdominal candidiasis

Spectrum of Disease Kullberg BJ, Arendrup M. NEJM 2015; 373: 1445-1456

Intra-Abdominal Candidiasis Common form of deep-seated candidiasis Poorly studied compared to candidaemia Accounts for ~10% of all cases of peritonitis Bacterial co-infection is common Co-infection in 2/3

Classification Vergidis et al. PLoS ONE. 2016; 11(4). e0153247 Primary peritonitis No apparent breach of the GI tract Secondary Peritonitis Follows perforations, surgical leaks, trauma or other pathological process Tertiary Peritonitis Persistence or recurrence of intra-abdominal infection following treatment Intra-Abdominal Abscess Localized infection resulting from pathological process or breach of the GI tract Infected Pancreatic Necrosis Infection of the non-vitalized pancreatic tissue Cholecystitis, cholangitis Vergidis et al. PLoS ONE. 2016; 11(4). e0153247

Risk factors Acquisition can be: Community-acquired Hospital-acquired Recurrent GI surgery GI tract perforations GI anastomosis leakage Prolonged broad-spectrum antibiotics Acute renal failure Total parenteral nutrition ICU stay Diabetes mellitus Immunosuppression Acquisition can be: Community-acquired Hospital-acquired Healthcare-associated Bassetti et al. Intensive Care Med. 2013; 39(12): 2092-106

Microbiology Candida albicans (65-82%) C. glabrata <20% C. tropicalis <10% C. parapsilosis <5% Other non-albicans Candida spp. ~2% Mixed Candida spp. ~5%

Clinical manifestations Fever Abdominal pain (+/- guarding/rebound tenderness) Nausea, vomiting Purulent discharge from abdominal drains Leucocytosis Electrolyte abnormalities Hypokalaemia, hypernatremia Acidosis Raised inflammatory markers Clinical presentation is similar to bacterial peritonitis Bacterial co-infection is common

Diagnosis Direct microscopy Non-culture based diagnostics Intra-operative peritoneal or abscess fluid Culture Peritoneal or abscess fluid Blood culture In situ drains Dialysis effluent Non-culture based diagnostics Serum β-D-Glucan Candida PCR

Treatment Source control Prophylaxis Drainage of abscesses/collections Repair of anatomical defects Antifungals Antifungal treatment has been shown to improve outcomes Echinocandin Fluconazole (if not critically ill) Prophylaxis Fluconazole in high-risk surgical patients Dupont et al. Arch Surg. 2002. 137 (12):134-6 Montravers et al . Crit Care Med. 2006; 34 (3): 646-52 Vergidis et al. PLoS ONE. 2016; 11(4). e0153247 Fluconazole: alternative that can be used in patients who are not critically ill, who have not been treated recently with fluconazole, and who are not considered likely to have a fluconazole-resistant isolate

Source control Drainage Percutaneous (CT-, ultrasound-guided) Transgastric Surgical procedures Laparotomy to repair anatomical defects

Prognosis Survival analysis by type of intra-abdominal candidiasis Early source control and antifungal treatment are associated with improved outcomes Mortality ~30% in recent studies Mortality higher in patients admitted to the ICU Vergidis et al. PLoS ONE. 2016;11(4): e0153247

Predictors of mortality Increased likelihood for survival: Septic shock High APACHE II* Score Presence of abscess Upper GI tract source Antifungal therapy Nosocomial peritonitis Inadequate source control *Acute Physiology and Chronic Health Evaluation II Dupont et al. Arch Surg. 2002; 137 (12):134-6 Montravers et al . Crit Care Med. 2006; 34 (3): 646-52 Vergidis et al. PLoS ONE. 2016; 11(4). e0153247

Summary Intra-abdominal candidiasis is as common as Candida bloodstream infections Mortality rates are comparable to that of candidaemia Early source control and antifungal treatment are associated with improved outcomes

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