RESISTANCE OF BACTERIAL BIOFILMS TO ANTIBIOTICS - A GROWTH-RATE RELATED EFFECT
RESISTANCE OF BACTERIAL BIOFILMS TO ANTIBIOTICS - A GROWTH-RATE RELATED EFFECT
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DOI：
10.1093/jac/22.6.777
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发表时间：
1988-12-01
影响因子：
5.2
通讯作者：
GILBERT, P
中科院分区：
文献类型：
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作者：
BROWN, MRW;ALLISON, DG;GILBERT, P
虽然关于生物膜对抗生素敏感性的直接研究相对较少，但最近的研究表明，作为粘附性生物膜而不是作为浮游细胞的生长可能会对敏感性产生深远的影响，这种耐药性可能有助于特定感染的顽固性。在这样的研究中，生物膜中铜绿假单胞菌和表皮葡萄球菌对妥布霉素的抗性以及表皮葡萄球菌对万古霉素的抗性相对于同等的浮游种群增加了20-100倍(Nickel等人，1985；Evans&Holmes，1987；Gristina等人，1987；Prosser等人，1987)。虽然生物膜在体内生长模式的重要性已经得到了很好的证明，但观察结果通常是在实验系统中进行的，例如关于抗生素敏感性的观察，例如Robbins装置(McCoy&Costerton，1982)，它不受生长速度的控制。在Robbins装置中，在适当的介质中活跃生长的培养物通过圆柱体，直到生物膜在其内表面形成(McCoy&Costerton，1982)，生物膜可以通过移除形成圆柱体壁的可伸缩活塞来定期采样。在这些关于抗生素敏感性的研究中，在几天后，将已建立的生物膜群体与通过该设备的细胞进行比较。这样获得的生物膜被描述为“由密集的细菌组成]细胞嵌入融合的生物基质中”(Gristina等人，1987年)，但通常每平方厘米只含有104个活细胞，其存活率低于10%(Nickel等人，1985年)。在对对照生物膜的发展进行了调查的地方，发现种群在建立后活细胞数量增长缓慢，如果有的话(Evans&Holmes，1987；Prosser等，1987)。这些数据提供了明确的证据，表明所研究的生物膜内的细胞生长非常缓慢，类似于静止相培养。另一方面，在这些研究中作为“对照”获得的浮游细胞已经处于生长的对数阶段，并且具有接近100%的存活率。由于已知生长速率是抗生素作用的主要调节因素，并且固定相细胞对许多抗生素的耐受性是众所周知的(Brown，1977；Brown&Williams，1985<；r，Tuomanen，Durack&Tomasz，1986a；Tuomanen等人，1986*；Gilbert Etal.，1987)，这些控制不仅不适当，而且具有误导性，因为不能将生长速度降低的影响与与生物膜本身相关的影响区分开来。
Whilst there have been relatively few direct studies of the antibiotic susceptibility of biofilms, it has recently been demonstrated that sensitivity may be affected profoundly by growth as an adherent biofilm, rather than as planktonic cells, and that such resistance might contribute towards the recalcitrance of particular infections. In such studies tobramycin resistance of Pseudomonas aeruginosa and Staphylococcus epidermidis and vancomycin resistance of S. epidermidis were increased 20-100 fold for biofilms relative to'equivalent'planktonic populations (Nickel et al., 1985; Evans & Holmes, 1987; Gristina etal., 1987; Prosser etal., 1987). Whilst the importance of the biofilm mode of growth in vivo is well documented, observations, such as these concerning antibiotic susceptibility, have generally been made in experimental systems, such as the Robbins device (McCoy & Costerton, 1982), which are uncontrolled with respect to growth rate. In the Robbins device, actively growing cultures in appropriate media are passed through a cylinder until a biofilm, which may be periodically sampled by removal of retractable pistons forming part of the cylinder wall, develops on its inner surface (McCoy & Costerton, 1982). In these studies of antibiotic susceptibility, established biofilm populations are compared, after a number of days, with those cells passing through the device. The biofilms so obtained have been described as," consisting of a dense mat of bacteria] cells embedded in a confluent biomatrix"(Gristina et al., 1987) but often contain as few as 104 viable cells per cm2 and represent percentage viabilities of less than 10 (Nickel etal., 1985). Where the development of control biofilms has been investigated, the populations are seen to increase only slowly in viable cell number, if at all, after establishment (Evans & Holmes, 1987; Prosser etal., 1987). These data present unequivocal evidence that the cells from within the biofilms studied are growing very slowly and resemble stationary phase cultures. Planktonic cells obtained as' controls' in these studies, on the other hand, have been in their logarithmic phase of growth and possess percentage viabilities close to 100. Since growth rate is known to be a primary modulator of antibiotic action and the recalcitrance of stationary phase cells to many antibiotics is well established (Brown, 1977; Brown & Williams, 1985< r, Tuomanen, Durack & Tomasz, 1986a; Tuomanen et al., 1986*; Gilbert etal., 1987), these controls are not only inappropriate but also misleading since the effects of reduced growth rate cannot be distinguished from those associated with the biofilm per se.