Krakowka S, Eaton K A, Leunk R D
Department of Veterinary Biosciences, College of Veterinary Medicine, Ohio State University, Columbus 43210, USA.
Antimicrob Agents Chemother. 1998 Jul;42(7):1549-54. doi: 10.1128/AAC.42.7.1549.
Gnotobiotic piglets infected with Helicobacter pylori were treated with various antimicrobials as monotherapy and dual therapy, and the results were compared to those for piglets treated with a triple-therapy regimen (bismuth subsalicyclate at 5.7 mg/kg of body weight, metronidazole at 4.4 mg/kg, and amoxicillin at 6.8 mg/kg four times a day [QID]). Clearance of infection was assessed after 7 days of treatment, and eradication was assessed following 7 days of treatment and a 14-day posttreatment observation interval. Monotherapy with amoxicillin, clarithromycin, and ciprofloxacin cleared and eradicated the organism from porcine stomachs; monotherapy with metronidazole cleared the infection and eradicated it from some piglets. Metronidazole-resistant microbes were recovered from treated piglets which cleared but did not eradicate the infection. Monotherapy with bismuth subsalicylate, erythromycin, nitrofurantoin, and tetracycline in the dosage range of 5.0 to 7.1 mg/kg QID was less than 100% effective in clearance and eradication, in that these drugs cleared and/or eradicated the infection from some of the piglets but did not eradicate the infection from all of the piglets. Monotherapy with an H-2 receptor antagonist (ranitidine) or a proton pump inhibitor (omeprazole) was ineffective at either clearance or eradication. In vivo dose titrations with several effective monotherapies were performed to determine the lowest effective in vivo dose of drug. In piglets, eradication was associated with a statistically significant decline in serum H. pylori-specific immunoglobulin M (IgM) antibodies; the titers of both IgA and IgG also declined, but the values were not statistically significant. For many antimicrobials, piglets are more sensitive indicators of clearance and eradication than humans. These data establish the H. pylori-infected gnotobiotic piglet as a useful model for the identification of novel antimicrobials for the treatment of this disease and for drug assessment during preclinical evaluations.
将感染幽门螺杆菌的无菌仔猪分别采用多种抗菌药物进行单药治疗和联合治疗，并将结果与采用三联疗法（碱式水杨酸铋5.7毫克/千克体重、甲硝唑4.4毫克/千克、阿莫西林6.8毫克/千克，每日4次[QID]）治疗的仔猪的结果进行比较。治疗7天后评估感染清除情况，治疗7天并经过14天的治疗后观察期后评估根除情况。阿莫西林、克拉霉素和环丙沙星单药治疗清除并根除了猪胃中的病原体；甲硝唑单药治疗清除了感染，并在一些仔猪中根除了感染。从清除但未根除感染的治疗仔猪中分离出了耐甲硝唑微生物。碱式水杨酸铋、红霉素、呋喃妥因和四环素在5.0至7.1毫克/千克QID剂量范围内的单药治疗在清除和根除方面的有效率低于100%，因为这些药物清除和/或根除了部分仔猪的感染，但并未根除所有仔猪的感染。H-2受体拮抗剂（雷尼替丁）或质子泵抑制剂（奥美拉唑）单药治疗在清除或根除方面均无效。对几种有效的单药治疗进行了体内剂量滴定，以确定最低有效体内药物剂量。在仔猪中，根除与血清幽门螺杆菌特异性免疫球蛋白M（IgM）抗体的统计学显著下降相关；IgA和IgG的滴度也下降，但数值无统计学显著性。对于许多抗菌药物，仔猪比人类更能敏感地反映清除和根除情况。这些数据表明，感染幽门螺杆菌的无菌仔猪是一种有用的模型，可用于鉴定治疗该疾病的新型抗菌药物以及在临床前评估期间进行药物评估。
