C. perfringens is a potentially dangerous gram positive anaerobic rod, causing disease through toxin release. The incidence has been estimated to be less than 2 per 100,000 [1] and mortality rates have been reported between 27% and 44% [1]. Recognized sources of C. perfringens bacteraemia include wound contamination and iatrogenic bowel leakage, and can be complicated by hemolysis and overwhelming infection if treatment is delayed [2].

Acute cholecystitis commonly presents with a syndrome of right upper quadrant abdominal pain, fever and leukocytosis, and is usually attributed to gallstones [3]. Common organisms associated with cholecystitis include Escherichia coli, Klebsiella spp. and Enterococcus faecalis [4]. Acalculous cholecystitis has a similar clinical picture but in the absence of gallstones. It accounts for 2–15% [5] of acute cholecystitis cases and often presents in critically ill patients or with severe systemic stress e.g., trauma, major surgery, shock or burns [6]. Acalculous cholecystitis is more frequently associated with Pseudomonas, Staphylococci including methicillin-resistant Staphylococcus aureus, Enterobacter, Bacteroides spp. and fungi [4].

We present a diagnostic dilemma of concurrent acalculous cholecystitis inaccurately identified on ultrasound and C. perfringens bacteraemia in a previously healthy individual, with implications for future diagnosis.

A 56-year-old male presented to the emergency department with a history of one day of severe chest and epigastric pain, fevers and rigors. His medical history included ischemic heart disease, peptic ulcer disease and gastroesophageal reflux disease.

On examination, he was febrile (39.4°C), demonstrated tachycardia of 110 beats per minute, tachypnea of 26 breaths per minute, an oxygen saturation of 92% on one litre of supplemental oxygen and was normotensive. His chest and abdominal examinations were normal.

An initial blood sample was hemolyzed prior to analysis. Subsequent blood tests revealed a mild neutrophilia, raised C-reactive protein (CRP) and thrombocytopenia (Table 1). All other blood levels including liver function tests were normal. Since a chest X-ray demonstrated no abnormality, a CT pulmonary angiogram was performed for suspected pulmonary embolism, however, the only salient findings were gallbladder wall thickening and a small volume of pericholecystic fluid. An abdominal USG suggested adenomyomatsis of the gallbladder without features of cholecystitis. Gallstones were not visualized on either scan. Empirical intravenous antibiotics (ceftriaxone 1 g and azithromycin 500 mg) were commenced.

The patient continued to be febrile overnight with mild right upper quadrant abdominal pain developing. The following morning, the CRP had increased and the platelet count had fallen further (Table 1). Preliminary blood cultures taken at time of presentation, demonstrated a C. perfringens bacteraemia at 30 hours from presentation, and antibiotics were changed to intravenous tazobactam/piperacillin 4.5 g and clindamycin 600 mg. This positive blood culture result and the location of abdominal pain greatly increased suspicion for biliary sepsis, and the patient was taken to theatre. Intraoperatively, a perforated and gangrenous gallbladder was removed laparoscopically and a cholangiogram demonstrated no filling defects. The patient received a single pack of pooled, irradiated platelets, due to refractory bleeding from the gallbladder fossa. Postoperatively, the thrombocytopenia had improved and the patient was discharged with oral antibiotics (amoxicillin/clavulanate 875/125 mg). Acute gangrenous cholecystitis without gallstones was confirmed on histopathology (Figure 1). At a two-week follow-up appointment, all blood abnormalities had resolved to within normal range (Table 1).

This case represents a clinical dilemma given the unusual presentation and difficult pathway to diagnosis. The diagnosis of acalculous cholecystitis was finally made based on intraoperative findings of a perforated and gangrenous gallbladder, the normal cholangiogram and the subsequent histopathologic analysis of the specimen. As outlined in Table 2, the commonly associated organisms vary between calculous, acalculous and emphysematous cholecystitis. Although Clostridium spp. has been associated with secondary emphysematous acalculous cholecystitis in critically ill patients or following antibiotics [3], no features suggestive of emphysematous acalculous cholecystitis including air in the gallbladder lumen or wall were seen on imaging in this case. In addition, the absence of a preceding physiological stress or immunocompromise is unusual in the development of both acalculous cholecystitis and C. perfringens bacteraemia.

Although no other case of acalculous cholecystitis and C. perfringens bacteraemia has been reported in human literature, there is a similar published case of a pig with undifferentiated sepsis, a necrotic gall bladder without gallstones on autopsy and hemolysis of initial blood samples [6]. A human case of C. perfringens bacteraemia with clinical suspicion of a biliary source, was attributed to gallstones, which were confirmed on endoscopic retrograde cholangiopancreatography [7]. These examples highlight the atypical presentation in our patient and the need to consider all clinical features when faced with a similar diagnostic dilemma.

The significance of the patient's thrombocytopenia remains unclear, however, a corresponding phenomenon has been reported in a retrospective cohort study of 93 patients with C. perfringens [1]. Additionally, hemolysis of an initial blood sample has been reported in another case of C. perfringens bacteraemia [8]. This may be attributed to toxin release [9]. However further exploration of these two associations is needed.

C. perfringens bacteraemia is a rare and potentially serious condition. Acalculous cholecystitis can occur despite abdominal ultrasonography suggesting an alternative diagnosis. This case highlights that acalculous cholecystitis can occur in patients without risk factors, and can be complicated by atypical bacteraemia, even in previously healthy individuals.

Dr Rhoda Cameron, Consultant Pathologist, Anatomical Pathology, Alfred Health, Melbourne, Victoria. Informed, written consent for the synthesis and publication of this case report was obtained from the patient, with thanks.

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