Role of fluconazole in the long‐term suppressive therapy of fungal infections in patients with artificial implants

Abstract

With the increased use of artificial implants the management of related infections has become an important challenge. Normally an infected implant would be removed. In many cases this might be contraindicated and drug treatment remains as the only alternative. As microbiological eradication is often impossible, especially in fungal infections at artificial implants (FIAI) long-term suppressive therapy might be required. The objective of this study was to determine the therapeutic value of fluconazole (F) in the management of FIAI. Clinical data of 56 patients (pts) with proven or suspected fungal infections and artificial implants (FIAI) subsequently treated with F were analyzed retrospectively. FIAI caused by species with intrinsic resistance to F have been excluded from the study. The following implants were involved: prosthetic valve endocarditis (PVE) 25 pts (44.6%), intraocular lenses (IL) 9 pts (16.1%), ventriculoperitoneal shunts (VPS) 6 pts (10.7%), knee prostheses (KP) 5 pts (8.9%), biliary stents (BS) 4 pts (7.1 %), venous access devices (VAS) 3 pts (5.4%), urinary stents (US) 2 pts (3.6%), breast implant and pacemaker 1 patient (1.8%) each. Underlying diseases were valve insufficiency (in PVE), cataract surgery (in IL), prematurity in newborns (in VPS), arthrosis (in KP), biliary obstruction (in BS), cystic fibrosis (in VAS), and obstructive renal calculi (in US). Candida species (C. spp.) were the most frequently detected causative agents with C. parapsilosis as the leading cause (n = 19; 33.9%). Furthermore C. albicans (n = 15; 26.8%), C. spp. and fungi not further specified (n = 8; 14.3%), C. tropicalis (n = 3; 5.4%), C. glabrata (n = 3; 5.4%), and C. lusitaniae (n = 1; 1.8%) were identified. Acremonium kiliense has been detected in 4 pts (7.1%), Cryptococcus neoformans in 2 pts (3.6 %). Histoplasma capsulatum was identified in 1 patient (1.8%). The maximum duration of treatment with F was lifelong with a maximum recorded duration of 4,5 years. The maximum dosage used was 750 mg/d or 50 mg/kg BW in premature infants. No major adverse events were observed. In conclusion, especially the excellent safety profile as well as the documented therapeutic experience justify the use of F as long-term suppressive therapy in FIAI. Higher dosages and even life-long treatment may be needed.

Susceptibility of Cryptococcus neoformans Biofilms to Antifungal Agents In Vitro

“…For instance, Walsh et al reported that C. neoformans could form biofilms in ventriculoatrial shunt catheters (35). In addition, several reports of C. neoformans infection of polytetrafluoroethylene peritoneal dialysis fistula and prosthetic cardiac valves highlight the ability of this organism to adhere to medical devices (6,7,26). In fact, the increasing use of ventriculoperitoneal shunts to manage intracranial hypertension associated with cryptococcal meningoencephalitis highlights the importance of investigating the biofilm-forming properties of this organism (2,13).…”

Case Report: Relief of Acute Obstruction of the Detour® Subcutaneous Pyelovesical Bypass

“…5 Especially in prosthetic tissues, the environmental factors are optimal in creating a nucleus for growth, aggregation, and ramification of mycelium. 6,7 In our patient, the Candida infection caused acute obstruction of the prosthetic ureter by forming fungus balls. obstructing the lumen of the prosthesis completely.…”

Fungal endocarditis

“…Therefore, we think that fluconazole therapy has no place in treating acute FE. However, there is increasing evidence that fluconazole could be administered as suppressive therapy to patients who successfully completed a full course of amphotericin B [47]. Animal studies have demonstrated that fluconazole combined with cyclosporine has a fungicidal effect superior to amphotericin B [48].…”

“…Chronic suppressive therapy of FE with oral fluconazole is increasingly used [47,50,51], although the efficacy of this strategy has never been proven. However, many patients, especially those who were not candidates for surgical interventions, were treated successfully for long periods with oral fluconazole after having completed a full course of amphotericin B.…”