Candida glabrata Acalculous Cholecystitis in an Immunocompetent Host

ABSTRACT

Acalculous cholecystitis (AC) is an inflammatory condition of the gallbladder without the presence of gallstones. Although far less common than calculus cholecystitis, AC is associated with a mortality rate 10 times higher than that of calculus cholecystitis. While normally due to bacterial pathogens, opportunistic ones such as the fungi Candida species (spp) can be rare causative agents of AC, typically observed in those with underlying malignancy or immunosuppression. In this study, we present an unusual case of an immunocompetent patient who was afflicted by fluconazole-resistant Candida glabrata AC. Our case highlights the complexity of this diagnosis and the challenges providers may encounter while treating the underlying infection.

INTRODUCTION

Acalculous cholecystitis (AC) is an acute disease of the gallbladder with a complex, multifactorial pathogenesis. It represents approximately 10% of the cases of acute cholecystitis in adults, but the mortality rate can be as high as 50%-60%, a striking contrast when compared with the mortality rate of less than 5% in calculus cholecystitis.¹ Primary pathophysiologic factors of AC are caused by gallbladder stasis and endothelial injury, which results in gallbladder distention, ischemia, and concentration of bile salts. Once this process takes place, AC is established and secondary infection with enteric pathogens is common. The most common causative pathogens are Escherichia coli, Enterococcus faecalis, Klebsiella species, Pseudomonas spp, Proteus spp, and Bacteroides fragilis.² The occurrence of this secondary infection can trigger a systemic inflammatory response ultimately resulting in sepsis.³

CASE DESCRIPTION

A 68-year-old African American man was admitted to the intensive care unit for septic shock with severe metabolic acidosis. His medical history was significant for tobacco use disorder, coronary artery disease, stroke, hypertension, hyperlipidemia, and heart failure. He had no history of chronic kidney disease, diabetes, or obesity. Before admission, he complained of increasing fatigue and significant abdominal pain exacerbated after eating. On the day of presentation, he took an afternoon nap and was later found unresponsive, prompting the arrival of emergency services.

On admission, the patient remained unresponsive and in shock. Initial laboratory results revealed a significant leukocytosis with white blood cells greater than 20 k/μL, lactic acid greater than 24 mmol/L, mildly elevated transaminases, and normal bilirubin levels. He was intubated and started on vasopressors, as well as vancomycin and piperacillin-tazobactam, and continuous renal replacement therapy. Blood, urine, and sputum cultures were collected. Imaging studies of his head and chest were unremarkable; however, an abdominal ultrasound revealed gallbladder wall thickening measuring up to 6.2 mm, gallbladder distention measuring up to 12.1 cm, and pericholecystic edema (Figure 1), and no cholelithiasis, all suspicious for AC. Given the lack of evidence for other possible sources of sepsis, he underwent percutaneous cholecystostomy placement, with gallbladder aspirate sent for culture. Preliminary culture displayed growth of many yeasts (no quantification given), prompting the addition of intravenous fluconazole. All other cultures remained negative without any growth.

Figure 1.

Right upper quadrant ultrasound: Top—echogenic sludge (arrows) and gallbladder distention measuring 12.1 cm (a). Bottom—gallbladder wall thickening measuring 6.2 mm.

Despite continued treatment, the patient remained unresponsive and showed no signs of improvement. Three days later, his final gallbladder aspirate culture grew a fluconazole-resistant strain of Candida glabrata (CG). He was started on micafungin monotherapy for 10 days. Unfortunately, despite prolonged treatment, he showed no signs of clinical improvement. The family decided to pursue palliative care, and the patient ultimately died.

DISCUSSION

CG is typically considered a nonpathogenic fungus with limited pathogenic potential for serious infections in humans. Recently, the increased use of immunosuppressive agents and broad spectrum antifungal agents has resulted in a notable rise in incidence of systemic infections caused by CG, seen almost exclusively in patients with significant immunosuppression.^4,5 Our patient was unique considering he was not on any immunosuppressive agents, and he had no obvious causes of immunosuppression before his presentation. While Candida albicans is the most common fungal species isolated from blood samples, CG is only the fourth most isolated within the Candida spp; despite its lower incidence rates, CG is associated with an equally high mortality rate as Candida albicans.⁶ CG is also of clinical relevance due to its innately increased resistance to antifungal agents, particularly the azole antifungals.⁷ Current guidelines suggest all infections caused by CG be treated with echinocandins.⁸

AC is most seen in hospitalized and critically ill patients. The clinical presentation of AC varies on the severity of the illness and the underlying predisposing conditions that contribute to its development. Disease onset is oftentimes insidious, and patients may initially present with sepsis, shock, or peritonitis due to more severe complications. The most reported complications of AC are gallbladder necrosis, gangrene, and perforation, all of which significantly increase morbidity; over 50% of patients afflicted by AC will ultimately develop gallbladder gangrene, greatly reducing their chances of survival.⁹

The diagnosis of AC may be challenging, particularly because critically ill patients are incapable of providing history, and that current imaging modalities are not specific enough to make the diagnosis alone.¹⁰ Current guidelines suggest obtaining abdominal ultrasound as the initial imaging modality.¹ Features suggestive of AC include sonographic Murphy sign, gallbladder wall thickening ≥4 mm, and/or pericholecystic fluid in the absence of any gallstones; the most reliable feature of AC on ultrasound is gallbladder wall thickening.⁹ There are little data to approximate the sensitivity of ultrasound for diagnosing AC; however, it has shown to have a specificity ranging between 89 and 100%.¹¹ Management entails supportive treatment, broad spectrum antimicrobial therapy, and source control either with cholecystectomy or gallbladder drainage. AC due to rare, multidrug resistant pathogens such as CG should be suspected in a patient who shows no signs of improvement despite prolonged broad spectrum antimicrobial therapy. Our patient showed minimal improvement with fluconazole therapy before cultures yielding CG. Ideally echinocandins would have been started at this time; however, due to low suspicion of such a rare infection in an immunocompetent patient, they were not.

CG-induced AC is an extremely rare condition. There are very few reported cases in current literature. Most cases describe a vague, nonspecific constellation of symptoms including fevers, abdominal pain, fatigue, and decreased appetite on initial presentation; however, these symptoms are not always present, and patients may even present asymptomatically. Most reported cases have ultimately resulted in the death of the patient. Currently, there are not sufficient data to suggest an accurate mortality rate of CG-induced AC.¹²

Timely recognition of AC is pertinent in critically ill patients with persistent sepsis when all other potential sources have been ruled out. The rise of antimicrobial-resistant pathogens requires clinicians to keep initial therapies broad; however, this approach paradoxically leads to enhanced pathogen resistance. Therefore, clinicians must acquire quality samples for pathogen identification and susceptibility testing to guide targeted treatment to ultimately optimize patient outcomes.

DISCLOSURES

Author contributions: Writing manuscript and literature research: A. Swaiti, J. Liu, K. Elhusseiny. Supervision case and writing manuscript: H. Ali, Z. Khan, R. Pamarthy, D. Hoo-Fatt.

Financial disclosure: None to report.

Informed consent was obtained for this case report.

ABBREVIATIONS:

AC

Acalculous Cholecystitis

CG

Candida glabrata

cm

centimeters

k/μL

thousands of cells per microliter

mm

millimeters

mmol/L

millimoles per liter

spp

species.