Discussion
CTRX, a third-generation cephalosporin antibiotic, is used worldwide to treat infectious diseases, including lower respiratory tract infections, bacterial meningitis, and skin and soft tissue infections, since it can penetrate tissues. CTRX-associated pseudolithiasis is a known complication, reported mainly in children. The mechanism is ascribed to a high CTRX concentration in the gallbladder bile, which is 20- to 150-fold higher than that in the serum. When the CTRX concentration in the gallbladder exceeds its threshold, CTRX can precipitate by binding to calcium ions secreted along with bile acids. Since CTRX can precipitate with calcium, CTRX-associated pseudocholelithiasis is principally composed of calcium-CTRX complexes 3.
Subcutaneous, deep muscle, and retroperitoneal bleeding are predominant bleeding sites in patients with AHA 1. However, gallbladder hemorrhaging and rupture are extremely rare entities, with only a few previously reported cases, even in patients using anticoagulants or with bleeding disorders. According to reports, mechanical irritation of the gallbladder wall due to preceding repeated cholecystitis can result in hemorrhaging from the gallbladder and its rupture 4,5. Yoshida et al. reported on the outcomes with CTRX-associated pseudocholelithiasis. The median intervals from CTRX administration to the diagnosis of CTRX-associated pseudocholelithiasis and from CTRX cessation to pseudolithiasis resolution were 10 days and 69 days, respectively. Events related to pseudocholelithiasis occurred in 29% patients, but most of the cases were improved with conservative treatment with CTRX cessation3. CTRX-associated pseudocholelithiasis can induce the development of cholecystitis, but no cases with fatal outcomes, including gallbladder hemorrhaging and rupture, have previously been reported.
In our case, AHA was a predisposing factor, leading to gallbladder hemorrhaging and rupture. The gallbladder is not structurally tolerant of ischemia, since it is maintained by the cystic artery, which is a terminal artery. Thus, high artery pressure due to a hematoma, boosted by AHA and local ischemia from massive blood loss caused an ischemic gallbladder wall, can trigger gallbladder rupture.
In conclusion, our case demonstrated that CTRX-associated pseudocholelithiasis can unexpectedly induce gallbladder hemorrhaging and rupture in a patient with a bleeding diathesis. Clinicians should be alert for CTRX-associated pseudocholelithiasis, which can cause a lethal outcome in patients with a bleeding disorder, even if CTRX is ceased as soon as pseudocholelithiasis is detected.