Citric Acid Confers Broad Antibiotic Tolerance through Alteration of Bacterial Metabolism and Oxidative Stress.

Antibiotic tolerance has become an increasingly serious crisis that has seriously threatened global public health. However, little is known about the exogenous factors that can trigger the development of antibiotic tolerance, both in vivo and in vitro. Herein, we found that the addition of citric acid, which is used in many fields, obviously weakened the bactericidal activity of antibiotics against various bacterial pathogens. This mechanistic study shows that citric acid activated the glyoxylate cycle by inhibiting ATP production in bacteria, reduced cell respiration levels, and inhibited the bacterial tricarboxylic acid cycle (TCA cycle). In addition, citric acid reduced the oxidative stress ability of bacteria, which led to an imbalance in the bacterial oxidation-antioxidant system. These effects together induced the bacteria to produce antibiotic tolerance. Surprisingly, the addition of succinic acid and xanthine could reverse the antibiotic tolerance induced by citric acid in vitro and in animal infection models. In conclusion, these findings provide new insights into the potential risks of citric acid usage and the relationship between antibiotic tolerance and bacterial metabolism.

Renal papillary necrosis with urinary tract obstruction: A case report.

BACKGROUND: Renal papillary necrosis (RPN) is a rare disease. It is difficult to distinguish RPN with urinary tract obstruction from upper urinary tract occupying lesions. We reported a case of RPN and made a definite diagnosis largely based upon its endoscopic characteristics. CASE SUMMARY: A 75-year-old woman presented with right flank pain, visible hematuria and a body temperature greater than 39 ℃. Laboratory investigations revealed leukocytosis with 12.7 × 10/L white blood cells and 93.6% neutrophils. Blood creatinine was 333 umol/L. Ultrasonography showed hydronephrosis of the right kidney and a right distal ureteric lesion. After urgent placement of right ureteral double J stent and treatment with antibiotics, the patient's symptoms and the blood abnormalities improved rapidly. Computed tomography urography showed the presence of multiple occupying lesions in the right pelvis. The endoscopic ureteroscopy revealed that renal papillary necrosis and the subsequent migration of sloughed papillae into the upper ureter and calyces. The sloughed papillae appeared like "cottons", which were whitish, soft, and irregularly-shaped without blood supply. In addition, the necrotic and sloughed renal papillae were removed by flexible ureteroscopy to prevent further obstruction. Pathological examination found that infarcted renal papillae were associated with inflammatory exudation. Three months after discharge, follow-up computed tomography urography showed no obvious lesions in the renal pelvis. CONCLUSION: This case revealed the endoscopic features of RPN. In addition, flexible ureteroscopy proves to be vital in diagnosis and treatment of RPN.