Microbe-metabolite interaction networks, antibiotic resistance, and in vitro reconstitution of the penile prosthesis biofilm support a paradigm shift from infection to colonization

Werneburg, Glenn T.; Lundy, Scott; Hettel, Daniel; Bajic, Petar; Gill, Bradley C.; Adler, Ava; Mukherjee, Sromona; Wood, Hadley M.; Angermeier, Kenneth W.; Shoskes, Daniel A.; Miller, Aaron W.

doi:10.1038/s41598-023-38750-1

Cited by 7 publications

(1 citation statement)

References 22 publications

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“…The potential biofilm that could form due to device contamination pre-operatively and intra-operatively has been proven to usually contain bacteria strains that have antibiotic-resistance genes [ 14 , 15 ]. This urges the need for efficient and effective methods beyond those available to prevent and treat biofilm formation and, in turn, mitigate antibiotic resistance in penile prosthesis infections.…”

Section: Discussionmentioning

confidence: 99%

Successful Conservative Therapy for Infected Penile Implants: A Case Series

Alkeraithe,

AlFakhri,

Alghafees

et al. 2023

Am J Case Rep

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Case series Patients: Male, 41-year-old • Male, 62-year-old • Male, 61-year-old • Male, 61-year-old Final Diagnosis: Infection Symptoms: Penile and scrotal pain Clinical Procedure: — Specialty: Urology Objective: Unusual clinical course Background: Traditionally, penile implant infections have been treated by removal followed by immediate or delayed replacement. The use of antibiotics in conservative therapy has recently attracted attention. Case Reports: We report our experience with 4 cases of infected penile implants managed conservatively. Case 1 was a 41-year-old with sickle cell anemia who presented with low-grade fever and purulent discharge that started 1 month postoperatively and lasted for 3 weeks. He had left graft after fibrotic tissue excision with 14-mm collection in the left corpus cavernosum. He was managed with IV pipracillin/tazobactam and vancomycin for 13 days. Follow-up after 23 weeks showed complete wound healing. Case 2 was a 62-year-old with diabetes who had purulent discharge that started 41 days postoperatively and lasted for 1 week. He received 5 days of IV vancomycin and gentamycin. Follow-up after 4 weeks showed marked improvement of the wound. Case 3 was a 61-year-old with diabetes and ischemic heart disease. He presented 30 days postoperatively with fever, puru-lent discharge for 5 days. He received a total of 10 days of IV vancomycin and gentamycin. Follow-up 3 weeks after discharge showed complete wound healing. Case 4 was a 61-year-old with diabetes and ischemic heart disease. He presented 1 month postoperatively with fever and pus discharge for 1 week. He completed 10 days of IV vancomycin and gentamycin. Follow-up after 1 week showed marked wound healing. Conclusions: Choosing patients with early superficial infected penile prosthesis for conservative management should be tailored to selected patients who does not have leukocytosis, signs of sepsis, high-grade fever, or an exposed device.

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Section: Discussionmentioning

confidence: 99%

Successful Conservative Therapy for Infected Penile Implants: A Case Series

Alkeraithe,

AlFakhri,

Alghafees

et al. 2023

Am J Case Rep

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Sacral neuromodulation device biofilm differs in the absence and presence of infection, harbors antibiotic resistance genes, and is reproducible in vitro

Werneburg,

Hettel,

Adler

et al. 2024

Neurourology and Urodynamics

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Introduction/PurposeSacral neuromodulation (SNM) is effective therapy for overactive bladder refractory to oral therapies, and non‐obstructive urinary retention. A subset of SNM devices is associated with infection requiring surgical removal. We sought to compare microbial compositions of explanted devices in the presence and absence of infection, by testing phase, and other clinical factors, and to investigate antibiotic resistance genes present in the biofilms. We analyzed resistance genes to antibiotics used in commercially‐available anti‐infective device coating/pouch formulations. We further sought to assess biofilm reconstitution by material type and microbial strain in vitro using a continuous‐flow stir tank bioreactor, which mimics human tissue with an indwelling device. We hypothesized that SNM device biofilms would differ in composition by infection status, and genes encoding resistance to rifampin and minocycline would be frequently detected.Materials/MethodsPatients scheduled to undergo removal or revision of SNM devices were consented per IRB‐approved protocol (IRB 20‐415). Devices were swabbed intraoperatively upon exposure, with controls and precautions to reduce contamination of the surrounding field. Samples and controls were analyzed with next‐generation sequencing and RT‐PCR, metabolomics, and culture‐based approaches. Associations between microbial diversity or microbial abundance, and clinical variables were then analyzed using t‐tests and ANOVA. Reconstituted biofilm deposition in vitro using the bioreactor was compared by microbial strain and material type using plate‐based assays and scanning electron microscopy.ResultsThirty seven devices were analyzed, all of which harbored detectable microbiota. Proteobacteria, Firmicutes and Actinobacteriota were the most common phyla present overall. Beta‐diversity differed in the presence versus absence of infection (p = 0.014). Total abundance, based on normalized microbial counts, differed by testing phase (p < 0.001), indication for placement (p = 0.02), diabetes mellitus (p < 0.001), cardiac disease (p = 0.008) and history of UTI (p = 0.008). Significant microbe‐metabolite interaction networks were identified overall and in the absence of infection. 24% of biofilms harbored the tetA tetracycline/minocycline resistance gene and 53% harbored the rpoB rifampin resistance gene. Biofilm was reconstituted across tested strains and material types. Ceramic and titanium did not differ in biofilm deposition for any tested strain.ConclusionsAll analyzed SNM devices harbored microbiota. Device biofilm composition differed in the presence and absence of infection and by testing phase. Antibiotic resistance genes including to rifampin and tetracycline/minocycline, which are used in commercially‐available anti‐infective pouches, were frequently detected. Isolated organisms from SNM devices demonstrated the ability to reconstitute biofilm formation in vitro. Biofilm deposition was similar between ceramic and titanium, materials used in commercially‐available SNM device casings. The findings and techniques used in this study together provide the basis for the investigation of the next generation of device materials and coatings, which may employ novel alternatives to traditional antibiotics. Such alternatives might include bacterial competition, quorum‐sensing modulation, or antiseptic application, which could reduce infection risk without significantly selecting for antibiotic resistance.

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