Anti-Infective Efficacy of Silver-Coated Medical Prostheses

Abstract

Medical prostheses constitute an indispensable component of modern health care. Like other approaches of medical intervention, the insertion of medical prostheses can be associated with serious complications. The ongoing advances in the mechanical properties of medical prostheses have not necessarily resulted in lower rates of prosthesis-related infection. Infection remains the most common serious complication of medical prostheses. For instance, vascular catheters account for most cases of nosocomial bloodstream infection [1], and catheter-related urinary tract infection is the most frequent nosocomial infection [2]. Two decades ago, infections associated with medical prostheses accounted for about half of all nosocomial infections [2]. Today, with their increasing use, medical prostheses are expected to cause a larger portion of cases of nosocomial infections, particularly in the subpopulations of immunocompromised, chronically ill, and elderly subjects. Infections associated with medical prostheses result in major morbidity and can be life-threatening. For instance, the mortality associated with prosthetic valve endocarditis ranges from 30% to 80% in patients with early-onset infection and from 20% to 40% in patients with late-onset endocarditis [3]. Often, infections associated with medical prostheses are very expensive to manage, and their cure requires removal of the infected prosthesis. For example, findings from the Dutch Trauma Trial indicated a mean cost of $22,000 (in 1991 dollars) to treat a patient who developed a deep wound infection after internal fixation of a closed fracture [4]. The difficulty and expense associated with the treatment of prosthesis-related infections have led to heightened interest in prevention. Because colonization of the prosthesis is a prelude to clinical infection, one important approach has been to coat the surface of the prosthetic devices with an antimicrobial substance. Although many such substances have been suggested to guard against prosthesis-related infection, only a very few have been demonstrated in prospective, randomized clinical trials to be clinically protective. A highly debated issue is the potential benefit of using silver-coated medical prostheses. Silver exhibits a rather broad-spectrum antimicrobial activity in vitro by binding both to microbial DNA, preventing bacterial replication, and to the sulfhydryl groups of the metabolic enzymes of the bacterial electron transport chain, causing their inactivation [5, 6]. In one form or another, silver molecules have been incorporated into the surfaces of a large variety of medical devices, including vascular, urinary, and peritoneal catheters, vascular grafts, prosthetic heart valve sewing rings, sutures, and fracture fixation devices. Despite the plethora of such silver-coated medical prostheses, their anti-infective efficacy has not been collectively addressed. The 2 main objectives of this comprehensive article are to review the in vitro, animal, and clinical experience with a variety of silver-coated medical prostheses (table 1) and to analyze the scientific reasoning for the anti-infective properties, or lack thereof, of silver-coated medical prostheses. In vivo efficacy of silver-coated medical prostheses. Unfortunately, all clinical trials of the efficacy of silver-coated bladder catheters studied catheter-associated bacteriuria rather than true clinical outcomes, such as symptomatic catheter-related urinary tract infection and bacteremia. Although the presence of bacteriuria is mandatory for the evolution of symptomatic urinary tract infection, bacteriuria remains asymp-tomatic in most cases. Furthermore, the various clinical trials used different definitions of catheter-associated bacteriuria, with concentrations ranging from ≥102 cfu/mL [7, 8] to ≥105 cfu/mL [9–12]. Such factors augment our inability to clearly assess the clinical impact of silver-coated bladder catheters. Bladder catheters coated with silver alone. Two earlier clinical trials conducted at the same institution had indicated that bladder catheters coated with silver alloy on both the external and internal surfaces significantly reduce the rate of catheter-associated bacteriuria, compared with uncoated catheters (10% vs. 37%–50%) [10, 11]. However, those 2 clinical trials were relatively small and offered no explicit description of the characteristics of enrolled patients. A recent meta-analysis also showed a significant benefit (the OR for developing catheter-associated bacteriuria was 0.24) from using bladder catheters with silver alloy coating on both the external and internal surfaces [13]. However, that meta-analysis was based on a total of 4 clinical trials, all conducted by the same group of investigators, including the 2 clinical trials mentioned above [10, 11] and 2 others reported in the form of a letter [7] and an abstract [12]. More recent, well-conducted, larger clinical trials demonstrated similar overall rates of ba