Domenico P, Landolphi D R, Cunha B A
Infectious Disease Division, Winthrop-University Hospital, Mineola, NY 11501.
J Antimicrob Chemother. 1991 Dec;28(6):801-10. doi: 10.1093/jac/28.6.801.
Bismuth subsalicylate (BSS), sodium salicylate, and bismuth nitrate were compared with respect to their effects on capsular polysaccharide (CPS) production, bacterial growth inhibition, and potentiation of aminoglycoside inhibition on strains of Gram-negative bacteria. At 250 microM, BSS reduced CPS production in Klebsiella pneumoniae cultures by greater than 90% in contrast to a 36% reduction by salicylate. At 500 microM, salicylate reduced CPS by 52%, versus a 70% reduction by bismuth nitrate. Substantial reduction of CPS production by BSS occurred before bacterial growth inhibition was observed. However, BSS at 250 microM decreased cell viability by 21%, and at 1 mM by 50%. Bismuth nitrate was equally inhibitory to cell growth. Salicylate at 1 mM did not affect bacterial cell counts. The susceptibility of selected Gram-negative bacteria to aminoglycoside antibiotics was studied in the presence of BSS or salicylate. Generally, salicylate at 2.5 mM reduced the concentration of aminoglycoside required to inhibit culture growth for 24 h (IC24) by two-fold. In contrast, 700 microM BSS reduced the IC24 for amikacin four-fold for a resistant K. pneumoniae strain. At 500 microM, BSS reduced the IC24 of gentamicin seven-fold for Salmonella typhimurium. Inhibitory concentrations of amikacin or tobramycin for Enterobacter cloacae or Serratia marcescens were also reduced seven-fold with 500 microM BSS. Bismuth nitrate reduced the IC24 of tobramycin by four-fold for E. cloacae. Thus, the profound effects of BSS on CPS production and aminoglycoside potentiation were due to the additive effects of bismuth and salicylate ions, whilst its effects on growth inhibition were due to the bismuth ion.
对碱式水杨酸铋(BSS)、水杨酸钠和硝酸铋在对革兰氏阴性菌菌株的荚膜多糖(CPS)产生、细菌生长抑制以及氨基糖苷类抑制增强方面的作用进行了比较。在250微摩尔浓度下,BSS使肺炎克雷伯菌培养物中的CPS产生减少了90%以上,相比之下水杨酸盐使其减少了36%。在500微摩尔浓度下,水杨酸盐使CPS减少了52%,而硝酸铋使其减少了70%。在观察到细菌生长抑制之前,BSS就使CPS产生大幅减少。然而,250微摩尔浓度的BSS使细胞活力降低了21%,1毫摩尔浓度时降低了50%。硝酸铋对细胞生长的抑制作用相当。1毫摩尔浓度的水杨酸盐不影响细菌细胞计数。在BSS或水杨酸盐存在的情况下,研究了所选革兰氏阴性菌对氨基糖苷类抗生素的敏感性。一般来说,2.5毫摩尔浓度的水杨酸盐使抑制培养物生长24小时所需的氨基糖苷类浓度(IC24)降低了两倍。相比之下,700微摩尔浓度的BSS使耐庆大霉素的肺炎克雷伯菌菌株的阿米卡星IC24降低了四倍。在500微摩尔浓度下,BSS使鼠伤寒沙门氏菌的庆大霉素IC24降低了七倍。500微摩尔浓度的BSS也使阴沟肠杆菌或粘质沙雷氏菌对阿米卡星或妥布霉素的抑制浓度降低了七倍。硝酸铋使阴沟肠杆菌对妥布霉素的IC24降低了四倍。因此,BSS对CPS产生和氨基糖苷类增强的深远影响是由于铋离子和水杨酸离子的加和作用,而其对生长抑制的影响则是由于铋离子。