|Year : 2023 | Volume
| Issue : 1 | Page : 27-31
Acute acalculous cholecystitis caused by Candida albicans secondary to COVID-19 infection: A case report
Haytham A Wali1, Deanne Tabb2, Saeed A Baloch3
1 Department of Pharmacy Practice, College of Clinical Pharmacy, King Faisal University, Al-Ahsa, Saudi Arabia; Department of Pharmacy Services, Piedmont Columbus Regional Midtown, Columbus, Georgia, USA
2 Department of Pharmacy Services, Piedmont Columbus Regional Midtown, Columbus, Georgia, USA
3 Division of Infectious Diseases, Department of Medicine, Piedmont Columbus Regional Midtown, Columbus, Georgia, USA
|Date of Submission||08-Oct-2022|
|Date of Acceptance||03-Dec-2022|
|Date of Web Publication||30-Mar-2023|
Dr. Haytham A Wali
Department of Pharmacy Practice, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
Source of Support: None, Conflict of Interest: None
Introduction: Acute acalculous cholecystitis is an acute gallbladder inflammation in the absence of cholelithiasis associated with high morbidity and mortality rates. Fungal organisms are an infrequent cause of gallbladder infections. Although many coronavirus disease-19 (COVID-19) patients reported gastrointestinal symptoms, there is little evidence of gallbladder and biliary tract involvement. we report a case of fungal acute acalculous cholecystitis secondary to COVID-19. Case Presentation: A 71-year-old man with a past medical history of benign prostatic hyperplasia, essential hypertension, and hyperlipidemia was admitted for COVID-19 and received appropriate treatment with dexamethasone, remdesivir, and convalescent plasma. The patient continued to be lethargic, weak, and had elevated inflammatory markers. He was transferred to the intensive care unit (ICU) for intubation and mechanical ventilation. The total bilirubin started to increase over the following days and reached 8 mg/dL (136.8 μmol/L). The ultrasound did not show cholelithiasis and the bile culture grew Candida albicans, indicating acalculous Candida cholecystitis. The patient had a significant deterioration in clinical status and passed away after being transferred to comfort care. Conclusion: Our case represents acute acalculous cholecystitis possibly secondary to COVID-19 infection that was resulted in an invasive fungal infection involving the gallbladder Future research could help facilitate a better pathophysiological understanding of gallbladder complications and provide a more precise explanation of the long-term effects of COVID-19.
Keywords: Acalculous cholecystitis, Candida albicans, case report, coronavirus disease-19, fungal infection
|How to cite this article:|
Wali HA, Tabb D, Baloch SA. Acute acalculous cholecystitis caused by Candida albicans secondary to COVID-19 infection: A case report. Saudi J Clin Pharm 2023;2:27-31
|How to cite this URL:|
Wali HA, Tabb D, Baloch SA. Acute acalculous cholecystitis caused by Candida albicans secondary to COVID-19 infection: A case report. Saudi J Clin Pharm [serial online] 2023 [cited 2023 Jun 10];2:27-31. Available from: http://www.sjcp.org/text.asp?2023/2/1/27/372927
| Introduction|| |
Acute acalculous cholecystitis (AAC) is a necro-inflammatory disease of the gallbladder with a multifactorial pathogenesis. It accounts for approximately 10% of all acute cholecystitis cases and is associated with high morbidity and mortality rates of around 30% (range, 10%–90%) with early or late diagnosis, respectively.
The etiology of AAC is multifactorial and likely results from bile stasis or ischemia (or both). Bile stasis can be caused by fasting, obstruction, postsurgical/procedural irritation, or total parenteral nutrition (TPN). The growth of organisms is ordinarily inhabited by the normal human bile salt concentration of 12% in the gallbladder. However, the presence of cholestasis reduces this concentration, which may permit bacteria to proliferate in the biliary system.,
Fungal organisms are an infrequent cause of gallbladder infections., Predisposing factors that could increase the risk of acute acalculous Candida cholecystitis include critical illness with prolonged hospitalization, malignancy, prolonged broad-spectrum antibiotic therapy, immunosuppression, treatment with histamine (H2)-receptor antagonists, gastric achlorhydria, diabetes mellitus, TPN, and intraabdominal surgery.,
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that has not been previously identified in humans and is responsible for the coronavirus disease-19 (COVID-19) infection. Many COVID-19 patients reported gastrointestinal symptoms such as anorexia, nausea, vomiting, and diarrhea. There have been a few cases reported an AAC associated with COVID-19.,,, However, these cases have reported a bacterial AAC secondary to COVID-19. Here, we report a case of fungal AAC secondary to COVID-19.
| Case Report|| |
This was a 71-year-old man with a past medical history of benign prostatic hyperplasia (BPH), essential hypertension, and hyperlipidemia who was admitted to Piedmont Columbus Regional Midtown (PCRM) in Columbus, Georgia, United States, with a chief complaint of shortness of breath that started a week ago and has been worsening within the 24 h before the hospital admission. The patient’s weight was 80.3 kg, and his body mass index (BMI) was 30.38 kg/m2. His vital signs on admission were the following: temperature (oral), 36.7°C (98°F); blood pressure, 157/80 mmHg; heart rate, 75 beats per minute; and respiratory rate, 22 breaths per minute. He had no history of tobacco, alcohol, or illicit drug use.
A nasopharyngeal swab was obtained to test for SARS-COV-2 using a reverse transcriptase polymerase chain reaction (RT-PCR) test (ID NOWTM COVID-19, Abbott Diagnostics Scarborough, Inc., Scarborough, Maine, United States), and the patient was found to be positive for COVID-19. His SARS-CoV-2 immunoglobulin G (IgG) antibody was found to be negative. On admission, he required five liters of oxygen (O2) through a nasal cannula (NC). The white blood cell (WBC) count on admission was 7.45 x 103/µL (normal range, 4 – 10.5 103/µL). Chest X-ray showed bilateral infiltrates and small pleural effusion in the right lung. Infectious diseases service was consulted, and the patient was started on intravenous (IV) remdesivir (VEKLURY, Gilead Sciences, Inc., Foster City, California) 200 mg IV on day 1, followed by 100 mg IV every 24 h for 5 days, dexamethasone 6 mg every 24 h for 10 days, and received a 250 mL of COVID-19 convalescent plasma under the Emergency Use Authorization (EUA) by the United States Food and Drug Administration (FDA). The oxygen requirement increased to 15 L/min through a Venturi mask with a 50% fraction of inspired oxygen (FiO2) and maintaining an O2 saturation at 93%. With the oxygen saturation not improving with the current oxygen therapy (the target O2 saturation was >94%), the patient changed to a high-flow nasal cannula (HFNC) with an oxygen flow rate of 40 L/min and 95% FiO2. However, the patient continued to be lethargic and weak, and had elevated inflammatory markers [Table 1]. The arterial blood gas (ABG) panel showed metabolic acidosis with respiratory compensation, and the patient appeared to be overcompensating due to hypoxia. Consequently, the patient was transferred to the intensive care unit (ICU) on day 5 of admission to the hospital for intubation and mechanical ventilation due to worsening respiratory status and the hyperinflammatory state (cytokine storm) secondary to COVID-19. The (1->3)-beta-D-glucan assay (Fungitell, Associates of Cape Cod, Inc., East Falmouth, Massachusetts) and the serum Aspergillus Galactomannan Enzyme Immunoassay (EIA) (Platelia™, Bio-Rad Laboratories, Redmond, Washington, United States) were obtained on that day.
After 48 h of being admitted to the ICU (Day 7 of hospitalization), the (1->3)-beta-D-glucan assay and the serum Aspergillus Galactomannan EIA were resulted negative, and the tests were repeated on that day for confirmation. Three days later (Day 10 of hospitalization; day 5 of ICU stay), the patient was started on cefepime 2 g IV every 12 h (the dose was renally adjusted for serum creatinine (SCr) of 2.13 mg/dL) and linezolid 600 mg IV every 12 h for suspected hospital-acquired pneumonia (HAP). The TPN was also initiated on that day. The following day (Day 11 of hospitalization; day 6 of ICU stay), the liver function panel showed elevated aspartate transaminase (AST) and alanine aminotransferase (ALT) values of 856 and 910 U/L, respectively, and linezolid was discontinued.
The next day (Day 12 of hospitalization; day 7 of ICU stay), the repeated (1->3)-beta-D-glucan was >500 pg/mL, but the serum Aspergillus galactomannan was undetectable. Because the AST and ALT were 243 and 395 U/L on that day, voriconazole could not be initiated, and the patient was started on amphotericin B lipid complex (ABELCET, Exelead, Inc., Indianapolis, Indiana) 300 mg IV every 24 h for possible COVID-associated pulmonary aspergillosis (CAPA). The endotracheal sputum culture obtained on the following day (Day 13 of hospitalization; day 8 of ICU stay) grew Candida albicans.
A subsequent comprehensive metabolic panel (CMP) the next day (Day 14 of hospitalization; day 9 of ICU stay) and its results is presented in [Table 1]. The total bilirubin continued to increase over the following days and reached 8 mg/dL (136.8 μmol/L), which raised the suspicion of cholecystitis. The abdomen ultrasound showed a gallbladder wall that measures 0.3 cm, no pericholecystic fluid collection, and a sludge that was not consistent with stones or blockage was present within the gallbladder. Acalculous cholecystitis was suspected, and since the patient was a nonoperative candidate, interventional radiology (IR) was consulted for a percutaneous cholecystostomy tube placement. Twenty milliliters of thick bile were aspirated and sent to the microbiology lab for Gram stain and culture, and it grew C. albicans susceptible to azoles, echinocandins, and amphotericin B. Consequently, amphotericin B was changed to micafungin (MYCAMINE, Astellas Pharma US, Inc., Northbrook, Illinois, United States) 100 mg IV every 24 h. The patient had a significant deterioration in clinical status and developed septic shock requiring multiple vasopressors. Eventually, the patient’s family opted for comfort care measures only, and the patient passed away two days later (Day 20 of hospitalization; day 15 of ICU stay).
| Discussion|| |
Our case represents AAC possibly secondary to COVID-19 infection that was resulted in an invasive fungal infection involving the gallbladder and the causative fungal organism was identified as C. albicans. Gastrointestinal symptoms have been reported with COVID-19. In a meta-analysis of 4243 patients with COVID-19, the prevalence of gastrointestinal symptoms was 17.6%, including loss of appetite, nausea/vomiting, diarrhea, and abdominal pain. Acalculous cholecystitis has been reported previously after acute infection with Epstein-Barr virus (EBV). Also, a case of AAC has been reported in a COVID-19 patient but with no pathogen identification.
Candida albicans in the gallbladder is thought to be a consequence of ascending migration of the organism within the biliary tract or hematogenous seeding during candidemia. In a retrospective chart review of 27 Patients with Candida spp. Isolated from the gallbladder or biliary tract, only 3 of 27 patients had candidemia, and 22 of 27 patients were colonized with Candida spp. At other sites, including sputum, urine, peritoneal fluid, catheter tip, and other sites. An epidemiological study also found that patients presenting with severe forms of COVID-19, especially those who required mechanical ventilation, were at increased risk of developing candidemia. It has been proposed that SARS-CoV-2 may increase intestinal permeability, potentially by causing damage to enterocytes and the epithelial layer. This disruption of the intestinal mucosal barrier in COVID-19 patients could be an additional risk factor for candidemia by facilitating the Candida species’ translocation from the gut lumen to the bloodstream.,, In our case, COVID-19 could have been associated with gut disruption resulting in Candida’s translocation and, consequently, dissemination to the gallbladder. Although there was no fungal growth in the blood cultures, the possibility that our patient experienced candidemia could not be ruled out due to prior amphotericin B exposure.
Moreover, the hyperinflammatory state associated with COVID-19 might be the cause of AAC, as one of the etiologies of AAC is the inflammatory process. SARS-CoV-2 has been associated with vascular inflammation, and vasoactive mediators can play a role in the pathogenesis of AAC by promoting ischemic gallbladder changes. The COVID-19 infection in our patient has reached the hyperinflammatory stage, which was evident by the elevated inflammatory markers [Table 1]. Our patient also had other multiple predisposing factors, including prolonged hospitalization, being on multiple broad-spectrum antibiotics, and receiving TPN.
Definitive treatment of AAC consists of cholecystectomy or, in poor surgical candidates, cholecystostomy. Alternatively, endoscopic retrograde cholangiopancreatography (ERCP) is an effective treatment option for patients who cannot tolerate surgery or cholecystostomy. In addition to drainage, patients on broad-spectrum antimicrobials can be narrowed based on the results of aspirated bile cultures. In our case, cholecystectomy was not feasible considering the patient’s COVID-19 infection and unstable condition. Therefore, cholecystostomy was performed through interventional radiology.
AAC can be associated with multiorgan dysfunction in critically ill patients., Critically ill patients admitted to ICUs have been found to have high mortality rates (38%–80%), likely because of disseminated Candida infection and candidemia., In a retrospective, unmatched, observational cohort study of 24 patients who underwent an open cholecystectomy for AAC, the median total Sequential Organ Failure Assessment (SOFA) score three days before cholecystectomy was 7.5 and increased to 10.5 (P < 0.0001) by the day of cholecystectomy, which indicated developing multiorgan dysfunction. Our patient had a multiorgan failure, which could be the consequence of the combination of COVID-19 infection and AAC.
| Conclusion|| |
We report a case of fungal AAC caused by C. albicans secondary to a COVID-19 infection. Our case could indicate that the disruption of the intestinal mucosal barrier along with the hyperinflammatory state (cytokine storm) associated with COVID-19 can be a risk factor for developing AAC. However, we acknowledge that this case cannot establish a causative relationship between COVID-19 and AAC. However, considering that the long-term complications of COVID-19 are still being studied, future research could help facilitate a better pathophysiological understanding of those complications and provide a more precise explanation of the long-term effects of COVID-19.
Financial support and sponsorship
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Conflicts of interest
There are no conflicts of interest.
Availability of data and material
Haytham Wali wrote the first draft of the manuscript, and all authors commented on previous versions. All authors read and approved the final manuscript.
The Columbus Regional Research Integrity Panel has confirmed that no ethical approval is required.
Consent to publish
The patient’s relatives have consented to submit the case report to the journal.
This work was published previously as a preprint on July 26, 2021, through the Research Square preprinting server with the following digital object identifier (DOI): 10.21203/rs.3.rs-319269/v1.
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