Pushkarev A M, Hamidullin K R, Papojan A O, Rakipov I G, Kazihinurov A A, Zagitov A R, Pavlov V N
Bashkir State Medical University, Department of Urology with a course of IDPO of the Ministry of Health of the Russian Federation.
GBUZ Republican clinical hospital named after G. G. Kuvatov, Ufa, Russia.
Urologiia. 2020 Dec(6):82-88.
To study the effect of prophylactic immunization with combined Staphylococcus-Proteus-Pseudomonas vaccine in combination with the probiotic Bacillus subtilis on the development of recurrent nephrolithiasis in patients after percutaneous nephrolithotomy (PCNL).
A total of 76 patients with a high infectious risk of stone formation in the early postoperative period after PCNL were included in the study. All patients received antibiotic therapy in accordance with the current guidelines as indicated. The patients were divided into 3 groups. In the comparison group (n=30), patients continued to receive antibiotics on the outpatient basis. In the group A (n=20), in addition to antibiotics, two-stage immunization with Staphylococcus-Proteus-Pseudomonas vaccine was performed. In the group B (n=26), additionally, patients received probiotic preparation "Bactisporin dry", which is a lyophilized spore-forming bacteria Bacillus subtilis strain 3N. All participants had urine culture and stone analysis using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. A study of specific antibodies level and factors of cellular and humoral immunity was carried out at specific time points. The duration of follow-up was 36 months.
The study revealed a difference in the pathogens isolated from urine and infection stones in the same patient. This convincingly suggests that pathogens form biofilms in the stones and are not detected during routine urine culture. The main pathogens isolated from the stones were Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus epidermidis and Klebsiella pneumonia. Microbial associations were found in 25.7% of cases. The Staphylococcus-Proteus-Pseudomonas vaccine demonstrated good immunogenicity, its antigenic components provided protective properties against autologous and opportunistic bacteria. In addition to the ability to induce a specific response to antigens, the vaccine stimulated the phagocytic activity of neutrophils. Immunization with the combined Staphylococcus-Proteus-Pseudomonas vaccine in combination with probiotic results in uncomplicated postoperative course in 84% of patients. Hospital-acquired infectious and inflammatory complications were seen in 16.2% of cases. The recurrence of stone formation in this group of patients within 36 months was 8.2%. In patients receiving only combined Staphylococcus-Proteus-Pseudomonas vaccine after PCNL, the postoperative period was uneventful in 65% of cases. The rate of upper urinary tract infection was 35%, while the inflammatory process was accompanied by mild clinical manifestations and quickly resolved. Recurrence of stone formation during the follow-up was seen in 18% of patients. In the control group, the proportion of uncomplicated cases in patients with nephrostomy tube was 40%, the development of pyelonephritis was noted in 60% of cases, and recurrent stones within 36 months were diagnosed in 46.7% of cases.
Our results emphasize that the role of an infectious factor in the development of recurrent nephrolithiasis after PCNL is often underestimated. The use of a specific vaccination and the Bacillus subtilis preparation in patients with a high infectious risk of recurrent stone formation allows to achieve a significant reduction in the recurrence rate (more than 5 times) compared to the control group during 36 months of postoperative follow-up.
研究葡萄球菌 - 变形杆菌 - 假单胞菌联合疫苗与益生菌枯草芽孢杆菌预防性免疫对经皮肾镜取石术(PCNL)后患者复发性肾结石形成的影响。
本研究纳入了76例PCNL术后早期结石形成感染风险高的患者。所有患者均按照现行指南进行抗生素治疗。患者分为3组。在对照组(n = 30)中,患者在门诊继续接受抗生素治疗。在A组(n = 20)中,除抗生素外,进行了两阶段的葡萄球菌 - 变形杆菌 - 假单胞菌疫苗免疫接种。在B组(n = 26)中,患者额外接受益生菌制剂“Bactisporin dry”,它是冻干的产芽孢细菌枯草芽孢杆菌3N菌株。所有参与者均进行了尿培养,并使用基质辅助激光解吸/电离飞行时间质谱法进行结石分析。在特定时间点进行了特异性抗体水平以及细胞和体液免疫因子的研究。随访时间为36个月。
研究发现同一患者尿液和感染结石中分离出的病原体存在差异。这有力地表明病原体在结石中形成生物膜,在常规尿培养中未被检测到。从结石中分离出的主要病原体为粪肠球菌、铜绿假单胞菌、表皮葡萄球菌和肺炎克雷伯菌。在25.7%的病例中发现了微生物组合。葡萄球菌 - 变形杆菌 - 假单胞菌疫苗显示出良好的免疫原性,其抗原成分对自体和机会性细菌具有保护特性。除了能够诱导对抗原的特异性反应外,该疫苗还刺激了中性粒细胞的吞噬活性。葡萄球菌 - 变形杆菌 - 假单胞菌联合疫苗与益生菌联合免疫使84%的患者术后病程顺利。医院获得性感染和炎症并发症发生率为16.2%。该组患者在36个月内结石形成复发率为8.2%。PCNL术后仅接受葡萄球菌 - 变形杆菌 - 假单胞菌联合疫苗的患者,65%的病例术后病程平稳。上尿路感染率为35%,炎症过程伴有轻度临床表现且迅速缓解。随访期间18%的患者出现结石复发。在对照组中,肾造瘘管患者无并发症的比例为40%,60%的病例发生肾盂肾炎,46.7%的病例在36个月内诊断为复发性结石。
我们的结果强调,PCNL后复发性肾结石形成中感染因素的作用常常被低估。在复发性结石形成感染风险高的患者中使用特异性疫苗和枯草芽孢杆菌制剂,与对照组相比,在术后36个月的随访期间可使复发率显著降低(超过5倍)。