Gorman S P, McGovern J G, Woolfson A D, Adair C G, Jones D S
Medical Devices Group, School of Pharmacy, Medical Biology Centre, The Queen's University of Belfast, UK.
Biomaterials. 2001 Oct;22(20):2741-7. doi: 10.1016/s0142-9612(01)00017-5.
Ventilator-associated pneumonia is a major cause of death in intensive care patients and the endotracheal tube, commonly fabricated from poly(vinyl chloride) (PVC), is acknowledged as a significant factor in this. Bacteria colonise the biomaterial, thereby adopting a sessile mode of growth that progresses to the establishment of an antibiotic-resistant biofilm by the accretion of a protective glycocalyx. This study examined the sequential steps involved in the formation of biofilm on PVC by atomic force microscopy and the concomitant development of resistance to an antibiotic (ceftazidime) and to a non-antibiotic antimicrobial agent (hexetidine). Staphylococcus aureus and Pseudomonas aeruginosa isolated from ET tube biofilm were employed. The surface microrugosity of bacteria growing in sessile mode on PVC decreased significantly (p < 0.05) over the period 4, 24, 48 h and 5 d. The progressive accretion of bacterial glycocalyx was readily visualised in micrographs leading to a smoother surface topography with time. The minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) for ceftazidime and hexetidine against planktonic (suspension) S. aureus were lower than for Ps. aeruginosa. Furthermore, sessile populations of S. aureus and Ps. aeruginosa on PVC exhibited greater resistance to both ceftazidime and hexetidine when compared to planktonic bacterial growth. The efficacy of the agents, determined by kill kinetics, against sessile bacteria was dependent on age, with established biofilms (> or = 24 h) significantly more resistant (p < 0.05) than early sessile populations (< or = 4 h). Importantly, for practice, even newly colonised bacteria (1 h) were significantly more resistant to antibiotic than planktonic bacteria. Hexetidine was significantly more active (p < 0.05) than ceftazidime on biofilms of both isolates, irrespective of age, with total kill within 24 h treatment. Hexetidine may offer promise in the resolution of infection associated with PVC endotracheal tubes.
呼吸机相关性肺炎是重症监护患者死亡的主要原因，通常由聚氯乙烯（PVC）制成的气管内导管被认为是其中的一个重要因素。细菌在生物材料上定殖，从而采用固着生长模式，通过积累保护性糖萼发展为形成抗生素耐药性生物膜。本研究通过原子力显微镜检查了PVC上生物膜形成所涉及的连续步骤，以及对一种抗生素（头孢他啶）和一种非抗生素抗菌剂（己脒定）耐药性的伴随发展情况。使用了从气管内导管生物膜中分离出的金黄色葡萄球菌和铜绿假单胞菌。在4、24、48小时和5天的时间段内，以固着模式在PVC上生长的细菌的表面微观粗糙度显著降低（p<0.05）。随着时间的推移，细菌糖萼的逐渐积累在显微照片中很容易观察到，导致表面形貌更光滑。头孢他啶和己脒定对浮游（悬浮）金黄色葡萄球菌的最低抑菌浓度（MIC）和最低杀菌浓度（MBC）低于对铜绿假单胞菌的。此外，与浮游细菌生长相比，PVC上的金黄色葡萄球菌和铜绿假单胞菌固着菌群对头孢他啶和己脒定都表现出更大的耐药性。通过杀灭动力学确定的这些药物对固着细菌的疗效取决于菌龄，已形成的生物膜（≥24小时）比早期固着菌群（≤4小时）耐药性显著更强（p<0.05）。重要的是，在实际应用中，即使是新定殖的细菌（1小时）对抗生素的耐药性也显著高于浮游细菌。己脒定在两种分离株的生物膜上均比头孢他啶活性显著更高（p<0.05），无论菌龄如何，在24小时治疗内可实现完全杀灭。己脒定在解决与PVC气管内导管相关的感染方面可能具有前景。
