Introduction

Male erectile dysfunction (ED) has been defined as the inability to attain or maintain penile erection sufficient for satisfactory sexual intercourse. Presently, the diagnosis and treatment of ED has evolved to the point that virtually every patient suffering from ED can successfully be treated. Nonsurgical and medical treatments can successfully treat a majority of men suffering with ED. However, there is still a subcategory of men with severe organic ED or significant structural abnormalities, who require surgical implantation of prosthetic devices for sexual function to be fully returned. Some authorities have noted that the frequency of penile prosthesis implantations has started to increase, after their reduction in number around 1998 with the introduction of Viagra (Pfizer Inc., New York, NY, USA).¹

A major concern for urologists who implant penile prostheses is the risk of infection, which occurs in 0.89–8.9% of cases with an overall incidence of approximately 2%.^{2,3,4,5,6,7,8,9,10} It is a customary practice to soak a penile prosthesis in antibiotic solutions for 5–10 min before implantation. This antibiotic application in theory may wash off any superficial microbes and provide short-term protection against infection. In an effort to create a window of protection for the long term, one prosthesis manufacturer (Mentor, Santa Barbara, CA, USA) has developed a proprietary hydrophilic penile prosthesis substrate coating that is designed to help inhibit bacterial adherence. Recent publications have reported on the efficacy of antibiotic-soaked, hydrophilic–coated substrates. Polyurethane central venous catheters were coated with a hydrophilic material and soaked in Teicoplanin, demonstrating antimicrobial activity against Staphylococcus aureus.¹¹ Likewise, hydrophilic-coated silicone hydrocephalus shunts soaked in various antibiotics exhibited a zone of inhibition against Staphylococcus epidermidis and Staphylococcus capitis.¹²

Both of the aforementioned studies demonstrate that incorporation of a hydrophilic coating prolongs antimicrobial activity of antibiotic-soaked specimens, compared to noncoated specimens. The present investigation in an in vivo rabbit model was undertaken to determine whether the hydrophilic (Resist™, Mentor, Santa Barbara, CA, USA) coating, applied to a prosthesis, would prolong the effect of antibiotics utilized intraoperatively.

Materials and methods

In this study, discs of penile prosthetic substrate material (Bioflex^®, Mentor, Santa Barbara, CA, USA) and Bioflex coated with Resist™ were compared to determine if the presence of Resist™ would prolong antibiotic activity. The activity of antibiotic-soaked Bioflex discs with and without Resist™ was evaluated by measuring the zone of inhibition following implantation in 4 to 6-month-old New Zealand white rabbits. Subsequently, the zone of inhibition values for the coated and uncoated populations were compared to one another via single-factor ANOVA, assuming equal variance.

Antibiotic selection

A survey of several urologists who frequently implant inflatable penile prostheses (IPP) revealed that gentamicin and bacitracin were the most commonly used antibiotics in the intraoperative solution used to soak the prosthesis before implantation. The antibiotic-soaking solution used for this study was composed of 2 g of gentamicin and 100 000 units of bacitracin in 1000 ml of saline.

Organism selection

Staphylococcus epidermidis is the organism cited as being the most frequently present when IPP devices become infected.^10,13,14,15 Staphylococcus aureus is the second most frequent infector organism. To a lesser extent, IPP device infections have also been linked to the yeast, Candida albicans, three-Gram-negative (Escherichia coli, Pseudomonas aeruginosa and Klebsiella) and one-Gram-positive (Enterococcus) bacteria. In order to capture the greatest percentage of organisms most likely to cause IPP infection, two of the Gram-positive (S. epidermidis and S. aureus) and two of the Gram-negative organisms (E. coli and P. aeruginosa) were used for this study.

Selection of specimen immersion time

All discs were soaked for 5–10 min, to match the usual soak time used during intraoperative prosthesis implantation.

Selection of animal model

Based on the size and demeanor of 4 to 6-month-old New Zealand white rabbits, the rabbit model was considered to be appropriate for implanting the Bioflex discs subcutaneously in the back region. The size of the rabbits (2.6–3 kg) allowed for the implantation of four discs per animal, considered desirable to help minimize animal-to-animal variability. The New Zealand white rabbits were sedated with ketamine hydrochloride (20 mg/kg i.m.) and anesthetized with pentobarbital sodium (30 mg/kg i.p.), and through an incision in the lower back, the discs were implanted subcutaneously in each animal.

Selection of time points

Data collected during in vitro bacterial adherence testing have shown that bacterial colonization and attachment will take place in less than 3 days.^16,17,18,19 Therefore, it was considered desirable to assess the activity of the antibiotic-soaked specimens before and after 3 days. To accomplish this goal, the following time periods were utilized: 0, 1, 2, 3 and 5 days following implantation.

Culture and antimicrobial susceptibility testing

This study was designed to determine the zone of inhibition of antibiotic-soaked, coated and uncoated Bioflex specimens, to demonstrate antibiotic efficacy, following elution in the rabbit model at various time points. All microorganisms were grown in pure cultures by standard techniques using blood agar plates. Standardized inoculums of the organisms to be tested were seeded onto the surface of Mueller–Hinton agar plates with or without 5% defibrinated sheep blood. The plates were incubated overnight, examined, and the diameters of the zones of inhibition measured to the nearest whole millimeter by a ruler. All procedural details were carefully standardized and properly controlled.

Sample size

The efficacy of the antibiotic solution against the four most common organisms in penile prosthesis infections was evaluated at five discrete time points, using coated and uncoated Bioflex discs implanted in rabbits. The first time point occurs at 0 days (ie, prior to implantation of the discs in the rabbit), and the other remaining four time points occurred while the discs were implanted. A total of six replicates each for the coated and uncoated populations were evaluated at each time point. Additionally, coated and uncoated specimens immersed in saline were evaluated at the same five time periods to serve as controls. The total number of antibiotic-soaked specimens evaluated for the coated and uncoated populations was 222 (111 each for the coated and uncoated populations). Additionally, 18 saline controls each were evaluated for coated and uncoated populations. Thus, a total of 240 specimens were evaluated in this study.

Study design

Study rabbits were divided into four groups, based upon implant duration: Group 1: 1 day, Group 2: 2 days, Group 3: 3 as and Group 4: 5 days. Each group of eight animals contained 32 discs (only four animals were in Group 4 for E. coli, S. aureus and P. aeruginosa). Two coated and two uncoated Bioflex discs were implanted subcutaneously in each rabbit's back. In order to assess the antibiotic activity (gentamicin (2 g) and bacitracin (100 000 U) in 1 l of saline) as a function of time in vivo, the implanted antibiotic-soaked discs were extracted at 1, 2, 3 and 5 days following implantation and the zone of inhibition against S. epidermidis, S. aureus, E. coli and P. aeruginosa in vitro was determined.

Statistical analysis

The zone of inhibition values for the coated and uncoated populations were compared via single-factor ANOVA, assuming equal variance. The P-values resulting from each ANOVA comparison are presented in Table 1 for S. epidermidis and for day 1 only for S. aureus, E. coli and P. aeruginosa. For all cases in which a P-value of less than 0.05 was obtained, statistical difference in populations is concluded.

Table 1 - Zone of inhibition (mm) (all values presented are averagestandard deviation).

Full table

Results

A summary of the data from all the experiments is demonstrated in Table 1. All microorganisms were inhibited by all discs, coated and uncoated, at day 0 after antibiotic soaking. From days 1–3, the coated discs demonstrated continued microbial inhibition compared to the uncoated discs against S. epidermidis.

Discussion

Antibiotics are used intraoperatively to minimize the ability of infection-causing microbes to reproduce and colonize foreign body surfaces. Of importance, this study demonstrated that the use of a hydrophilic coating (Resist™) as a penile implant coating does not reduce the effectiveness of antibiotic soaking prior to implantation. This allows the surgeon to continue to perform the same surgical technique of prophylactically soaking the penile implant intraoperatively.

Coated discs demonstrated a sustained inhibition against S. epidermidis, up to 3 days. This effect may prevent the colonization of S. epidermidis to penile implants and thereby reduce the chance of prosthetic infection. The etiology of this inhibition is based on the ability of the hydrophilic Resist™ coating to absorb water readily. Consequently, if the coated device is soaked in an antibiotic solution prior to implant, it will contain some quantity of antibiotic at the time of implantation, which will then be eluted over a specified time period, for example, 3 days. This property also allows the implanting surgeon to select antibiotics at the time of implantation. If a hospital-acquired micro-organism develops resistance to a specific antibiotic, an alternative antibiotic can be selected to address an emerging pattern of microbial resistance. While this study showed that the Resist™ coating prolonged the effect of antibiotic activity against only S. epidermidis, selecting alternative antibiotic solutions may provide a similar result with other organisms.

Another prosthesis manufacturer (American Medical Systems, Minnetonka, MN, USA) has recently introduced a prosthesis coating (InhibiZone™), in which a combination of rifampin and minocycline has been incorporated.²⁰ InhibiZone slowly releases its antibiotics over 10–14 days, thus there is a theoretical concern that a patient may develop an allergic reaction. The number of InhibiZone™-coated prostheses implanted to date is too low to determine at this time if there is a statistical benefit. Continued assessment of accumulated data will allow us to determine statistical efficacy.

In the present study, these data corroborate those of Jansen and Boelan, who demonstrated the effectiveness of hydrophilic-coated substrates in prolonging the antimicrobial activity of antibiotic-soaked specimens, compared to noncoated specimens. Therefore, combined with the Resist™ coating's long-term ability to inhibit bacterial adherence, the short-term elution of antibiotic(s) from a Resist™-coated penile implant that has been soaked in an antibiotic solution prior to implantation may reduce the rate of implant infection.

An important caveat is that introduction of any new microbe-resisting coating should not allow an implanting surgeon to reduce his vigilance, sterile technique, and use of antibiotics to prevent prosthetic infections. Despite the use of antibiotic coating and Resist™, a larger number of prosthesis implantations will need to be performed, followed over time, and analyzed in order to demonstrate statistically a significant benefit. In the meantime, the introduction of a new coating, that both inhibits microbial adherence and incorporates the antibiotic(s) used in the soaking medium, may provide the patient some added protection from prosthesis infection.

References

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Acknowledgements

Supported in part by an unrestricted educational grant from Mentor Corporation, Santa Barbara, CA.