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Do Antifungals and Local Anesthetics Affect the Efficacy of Antibiotic Dipping Solution?
By: Kirtishri Mishra, MD; Laura Bukavina, MD, MPH; Nannan Thirumavalavan, MD; Shubham Gupta, MD; Aram Loeb, MD | Posted on: 01 May 2021
Inflatable penile prostheses (IPPs) have been available as an advanced option for treatment of erectile dysfunction (ED) for over 40 years. While we have made major advancements, infection remains one of the major concerns with an implantable device of any sort. Historically, infection rates for IPPs have been quoted to be ∼5%; however, with the routine utilization of antibiotic coated prostheses these rates have dropped to ∼1% to 3% as cited in some studies.1-3 Furthermore, providers routinely utilize antibiotic dipping solutions intraoperatively to prevent postoperative infection. The practice of intraoperative dipping solution has evolved to include a wide array of antibiotics, and even local anesthetics. The use of local anesthetic dipping solutions is due largely to the national opioid crisis, which has been declared an epidemic in the last decade.4
The previous in vitro studies on the efficacy of intraoperative dipping solutions have found them to have no inhibitory effects on the efficacy of concurrent antibiotic function. However, these studies have been underpowered in regard to the number of organisms studied, the number of antibiotics evaluated, the lack of multiple strains tested, the absence of a rigorous scientific method that standardizes the quantity of antibiotics on each of the discs, the methodology to control the confluency of the plated organisms, and lastly the evaluation of fungal organisms. In addition, the previous studies have not evaluated the elution time of these dipping solutions over time.5,6
Our goals for this study were 1) to determine whether routine usage of local anesthetic and antifungal dipping solution decreases antibiotic efficacy, and 2) to determine the length of time that the prosthesis coating elutes the dipping solution over the course of 72 hours. We elected to use the Coloplast Titan® device with a hydrophilic coating (HydroVantage™), which allows us to control the type and concentration of the dipping solution. The table lists the antibiotics and antifungal utilized, along with their concentrations.
Strains of 4 different species of bacteria and 1 fungus were prepared in a standardized confluency. A standardized and sterile protocol was used to punch out 6 mm circular discs from the reservoir of a Coloplast Titan device. The discs were submerged in a standardized concentration of antimicrobials (see table) and plated. The zone of inhibition (ZOI) was measured at 24, 48 and 72 hours. Five repetitions of each organism were performed, and the mean ZOI was calculated. Saline and dimethylsulfoxide (DMSO) were used as control on each plate. In all, over 1,700 discs were plated and evaluated for the study.
Figure 1 shows the ZOI for each organism based on the antibiotics utilized. Larger ZOI means that the antibiotic is more effective in suppressing/inhibiting the growth of that organism. For Escherichia coli and Pseudomonas aeruginosa the ZOIs for trimethoprim-sulfamethoxazole (Bactrim®) and vancomycin with piperacillin-tazobactam (Zosyn®) were superior to rifampin with gentamicin. The addition of bupivacaine or amphotericin B (AmB) did not significantly affect the efficacy of any of the antibiotics in a positive or negative way; however, it did expand the coverage significantly against Candida albicans when utilized with rifampin and gentamicin combination. Unlike the previous organisms, rifampin with gentamicin was more effective against Staphylococcus epidermidis compared to the other antibiotics. Of note, there were 2 strains of E. coli and 1 strain of Staphylococcus aureus that were completely resistant to all antibiotic permutations. These strains were excluded to perform the analysis; however, it raises an important point about the developing antibiotic resistance across species and the need for customization of antibiotics based on community antibiograms.
Table. Concentrations of coating solutions utilized in the study.
Solution | Concentration |
---|---|
Bactrim (trimethoprim/sulfamethoxazole) | Trimethoprim 80 mg Sulfamethoxazole 400 mg (80 TMP/400 SMX per 5 mL 80/16 g/mL) |
Rifampin | 10 mg/mL |
Gentamicin | 1 mg/mL |
Amphotericin B | 0.1 mg/ mL |
Vancomycin | 1 mg/mL |
Zosyn (piperacillin/tazobactam) | 225 mg/mL |
Bupivacaine | 0.5% (5 mg/mL) |
Figure 2 displays the ZOI against each organism over the course of 72 hours. Overall, all antibiotics lost efficacy against the organisms over the course of 72 hours; however, rifampin demonstrated the greatest inhibition of S. epidermidis and S. aureus over a 72-hour period. Amphotericin B also significantly increased the efficacy against C. albicans during this time.
Overall, there are a few conclusions that we would like to highlight from this study. First, this study provides us with a robust validation of intraoperative utilization of local anesthetics. Based on the presented data in the in vitro model, we can conclude that the addition of local anesthetics does not negatively impact the efficacy of other antibiotics. If fact, it may have some weak antifungal and antibacterial properties. Secondly, the addition of antifungal solution does not negatively impact the efficacy of antibiotics. The utilization of amphotericin B significantly improved the antifungal coverage against C. albicans. Lastly, our temporal data identified that the efficacy of drug elution decreases over time, with little to no therapeutic elution at 72 hours. However, among the compounds tested, it appears that rifampin had the longest effect as compared to others. Bactrim appears to be the most efficacious antibiotic against the tested organisms.
It is important to discuss the 3 strains of bacteria (2 of E. coli and 1 of S. aureus) that were completely resistant to all antibiotics. While these organisms were excluded for the sake of the analysis, these strains may represent a growing cohort of common pathogens that may be found in health care setting and may infect prostheses. For this reason, the authors of this study strongly urge implanters to study their community antibiogram to determine if there are resistant variants of common pathogens that may require intraoperative and postoperative coverage. This needs to be considered for fungal organisms also, as there is growing literature that fungal and bacterial organisms may operate in symbiosis to create more virulent strains and resistant organisms. Ultimately, these findings need to be validated in a clinical setting; however, we hope that this study provides a scaffolding for future investigators to tailor their studies and clinical practice.
- Cosentino M, Bianco M, Ruiz-Castañé E et al: Treatment of penile prosthesis implant’s infection. Urol Int 2020; 104: 542.
- Hebert KJ and Kohler TS: Penile prosthesis infection: myths and realities. World J Mens Health 2019; 37: 276.
- Mulcahy JJ: Current approach to the treatment of penile implant infections. Ther Adv Urol 2010; 2: 69.
- Kiechle JE and Gonzalez CM: The opioid crisis and urology. Urology 2018; 112: 27.
- Wilson SK, Salem EA and Costerton W: Anti-infection dip suggestions for the Coloplast Titan inflatable penile prosthesis in the era of the infection retardant coated implant. J Sex Med 2011; 8: 2647.
- Lokeshwar SD, Horodyski L, Lahorewala SS et al: The effect of bupivacaine on the efficacy of antibiotic coating on penile implants in preventing infection. Sex Med 2019; 7: 337.