Jossart G H, Canafax D M, Erdmann G R, Lovdahl M J, Russlie H Q, Juhn S K, Giebink G S
Otitis Media Research Center, School of Medicine, University of Minnesota, Minneapolis 55455.
Pharm Res. 1994 Jun;11(6):860-4. doi: 10.1023/a:1018933925707.
Antimicrobial treatment failures in children with acute otitis media and concomitant viral respiratory tract infection prompted us to study the effects of influenza A virus infection on middle ear antimicrobial drug penetration. Using a chinchilla model of Streptococcus pneumoniae we compared middle ear elimination rates in 4 groups of chinchillas: (1) control, (2) influenza A virus inoculation alone intranasally, (3) both influenza A and S. pneumoniae inoculation directly into the middle ear, and (4) S. pneumoniae inoculation alone into the middle ear. After infection was established, a solution containing amoxicillin, sulfamethoxazole, and trimethoprim was instilled into the middle ear and removed 4 hours later. The rate constant of elimination and half-life were calculated from measured drug concentrations initially and at 4 hours. S. pneumoniae infection alone significantly shortened the middle ear elimination half-life compared with the control group: amoxicillin, 2.65 +/- 0.73 vs. 6.63 +/- 2.55 hr; sulfamethoxazole, 1.75 +/- 0.28 vs. 2.74 +/- 0.6 hr; and trimethoprim, 1.06 +/- 0.14 vs. 1.56 +/- 0.34 hr (n = 16 ears, p values all < 0.01). The combined influenza virus and S. pneumoniae infection significantly lengthened the half-life compared with the S. pneumoniae infection alone: amoxicillin, 5.65 +/- 6.44 vs. 2.65 +/- 0.73 hr; sulfamethoxazole, 2.5 +/- 0.85 vs. 1.75 +/- 0.28 hr; and trimethoprim, 1.26 +/- 0.42 vs. 1.06 +/- 0.14 hr (n = 16 ears, p values all < 0.01). Influenza virus produced the longest half-lives for all 3 antimicrobials: amoxicillin 25.52 +/- 14.96 hr; sulfamethoxazole, 5.46 +/- 0.87 hr; and trimethoprim, 2.57 +/- 0.75 hr.(ABSTRACT TRUNCATED AT 250 WORDS)
急性中耳炎合并病毒性呼吸道感染患儿的抗菌治疗失败促使我们研究甲型流感病毒感染对中耳抗菌药物渗透的影响。我们使用肺炎链球菌的栗鼠模型，比较了4组栗鼠的中耳清除率：（1）对照组；（2）经鼻单独接种甲型流感病毒；（3）中耳直接接种甲型流感病毒和肺炎链球菌；（4）中耳单独接种肺炎链球菌。感染确立后，将含有阿莫西林、磺胺甲恶唑和甲氧苄啶的溶液滴入中耳，并在4小时后取出。根据最初和4小时时测得的药物浓度计算清除速率常数和半衰期。与对照组相比，单独的肺炎链球菌感染显著缩短了中耳清除半衰期：阿莫西林，2.65±0.73小时对6.63±2.55小时；磺胺甲恶唑，1.75±0.28小时对2.74±0.6小时；甲氧苄啶，1.06±0.14小时对1.56±0.34小时（n = 16只耳朵，所有p值均<0.01）。与单独的肺炎链球菌感染相比，流感病毒和肺炎链球菌联合感染显著延长了半衰期：阿莫西林，5.65±6.44小时对2.65±0.73小时；磺胺甲恶唑，2.5±0.85小时对1.75±0.28小时；甲氧苄啶，1.26±0.42小时对1.06±0.14小时（n = 16只耳朵，所有p值均<0.01）。流感病毒使所有3种抗菌药物的半衰期最长：阿莫西林25.52±14.96小时；磺胺甲恶唑，5.46±0.87小时；甲氧苄啶，2.57±0.75小时。（摘要截断于250字）
