A case of recurrent acute cholecystitis caused by Actinomyces odontolyticus, rare actinomycosis

Actinomyces species are gram-positive, obligate anaerobic rods that colonize human’s upper respiratory tract, gastrointestinal tract, and female reproductive organs [1]. More than 30 species of Actinomyces have been identified to date and A. israelii is the most common pathogen [1].

In actinomycosis, intra-abdominal infections account for about 20%, and the most common site of infection is the ileum. There are few cases of cholecystitis due to Actinomyces species reported. To the best of our knowledge, our case must be the first case of cholecystitis caused by A. odontolyticus.

A 75-year-old Japanese man came to our hospital with fever, chills, and right hypochondrial pain. One and three years ago, this patient was already diagnosed twice with acute cholangitis and cholecystitis and then underwent endoscopic retrograde biliary drainage thirty-nine days before admission to our hospital. We demonstrated gram-positive rods, and gram-negative rods with Gram stain; namely A. hydrophilia and E. faecalis grew in the culture with no gram-positive rods. When the patient was transferred to our hospital, his body temperature was 39.9 °C, and he had tenderness in the right costal region. Blood tests showed white blood cell counts 23,700 /μL, C-reactive protein 23.2 mg/dL, aspartate aminotransferase 63 U/L, alanine aminotransferase 51 U/L, alkaline phosphatase 233 U/L, and γ-glutamyl transpeptidase 82 U/L. Contrast-enhanced CT of the abdomen showed an enlarged and multifocal gallbladder, intrahepatic perforation and abscesses around the gallbladder, some perforating into the right lobe of the liver and forming liver abscesses. But there was no obstruction of the biliary tract (Fig. 1). We diagnosed him with acute cholecystitis and liver abscess and then administered piperacillin/tazobactam. On the second day of admission, we decided to put cholecystectomy on hold to prioritize treatment of the liver abscess, and we implemented percutaneous transhepatic gallbladder drainage. Gram stain of the bile revealed gram-positive rods and gram-positive cocci (Fig. 2), which we identified as A. odontolyticus and MRSA. We also detected MRSA in the blood culture collected on the first day of admission. Judging from the culture results, we changed piperacillin/tazobactam to ampicillin/sulbactam and vancomycin. Blood cultures were negative on the fourth day of hospitalization. We performed laparoscopic cholecystectomy on the 14th day of hospitalization. The pathology of the gallbladder showed no evidence of malignancy. The patient got well. On the 20th day of hospitalization, we changed antibiotics to amoxicillin/clavulanate and linezolid, and after that, the patient was discharged safely. We administered antibiotics for a total of 5 weeks. After antibiotics were completed, he had no acute cholecystitis and liver abscess recurrence.

Actinomyces species are gram-positive, obligate anaerobic bacteria that infect various parts of the human organs [2]. The most common site of Actinomyces infections is a cervicofacial area, and other locations include the central nervous system, chest, and pelvis. Hepatobiliary infection is rare and accounts for 5% of all Actinomyces infections [2].

Only 22 cases of cholecystitis caused by Actinomyces species have been reported in English literature (Table 1). As far as we know, this is the first case in which A. odontolyticus was the causative organism [3‐15]. A. naeslundii was the most common causative organism seen in 7 cases [3‐5], and A. israelii in 3 cases [6, 7]. The other 12 cases were pathologically diagnosed with Actinomycosis. These results were consistent with the fact that it was difficult for Actinomyces other than A. naeslundii to survive in an environment of bile salts [8]. In this case, we detected A. odontolyticus in bile cultures. We assume that coinfected MRSA consumed oxygen and created an anaerobic environment where A. odontolyticus could grow. When A. naeslundii was the causative organism, it was the single pathogen in 6 of 7 cases (85.7%) [3‐5]. On the other hand, in the cases of A. israelii, 2 of 3 cases (66.7%) were infected with another bacteria; Pseudomonas aeruginosa was detected in one case [6], and Pseudomonas aeruginosa and Haemophilus aprophilus were seen in another case [7].

Gram stain found gram-positive rods in 12 cases [8‐10]. Of the 12 cases, six (50%) were positive for Actinomyces in culture [3, 10]. The mean age of the 22 patients was 63.1 years old, 14 cases (63.6%) had gallstones [3‐6, 8, 10‐14], and only 2 cases (9.1%) had a liver abscess [6, 15]. Of the 22 patients, six had a history of cholecystitis. Furthermore, one recurrent cholecystitis a few weeks after ending treatment was later proven to be caused by Actinomyces, as in our case [11]. Once the source of infection is controlled, the recommended treatment duration for acute cholecystitis is generally up to 7 days, even in severe cases [15]. However, in the case of cholecystitis caused by Actinomyces, the mean duration was 109 days in 22 patients because the appropriate duration of treatment for Actinomyces cholecystitis has not been established. Many cases underwent the treatment for long periods, like other actinomycosis such as lung infections.

Gram stain for Actinomyces visualizes and characterizes the presence of gram-positive rods with an elongated radial pattern [1]. However, as in another case of liver abscess caused by A. odontolyticus reported earlier [16], in this case, A. odontolyticus did not reveal a Gram stain with a typical elongated radial pattern. Thus, it may be difficult to distinguish A. odontolyticus from other gram-positive rods by Gram stain of bile. Furthermore, considering the low positive rate of bile culture in cholecystitis caused by Actinomyces, we may miss cholecystitis caused by Actinomyces. Even if the culture were negative, Actinomyces species should be considered the causative microorganism.

In conclusion, this is the first report of acute cholecystitis caused by A. odontoliticus. As cholecystitis related to A. odontoliticus is a rare condition, we may have been overlooked it because of the low positivity of bile culture and the absence of the typical elongated radial pattern on Gram stain. Furthermore, missing Actinomyces may be related to recurrent cholecystitis that may recall us Actinomyces infection.