Peritonitis represents a significant complication of peritoneal dialysis (PD) and can result in severe consequences, including hospitalization, PD catheter extraction, and the necessity for permanent hemodialysis (Htay et al., 2018). The common pathogens of PD-associated peritonitis are predominantly Gram-positive and Gram-negative bacteria (Kim et al., 2004; Whitty et al., 2017). Conversely, fungal infections, particularly those caused by Fusarium spp., are infrequent (Hu et al., 2019; Kanjanabuch et al., 2022). In this study, we report on a case of the use of oral voriconazole for the treatment of PD-associated Fusarium peritonitis.

A 61-year-old woman weighing 38.1 kg, who works as a farmer and had been undergoing continuous ambulatory peritoneal dialysis (CAPD) for over 8 years, presented with a 5-day history of abdominal pain, diarrhea, and vomiting, and then gradually developed cloudy PD effluent. Laboratory findings revealed a white blood cell (WBC) count of 12.6 × 10⁹/L, a neutrophil (NEU) count of 11.07 × 10⁹/L, and NEU% of 87.5%. Her C-reactive protein (CRP) level was 102.5 mg/L. Analysis of the PD effluent demonstrated turbidity with a WBC count of 4,044/μl (90% NEU). The admission diagnosis was PD-related peritonitis and chronic kidney disease (CKD 5).

Upon admission, empirical treatment with intraperitoneal (IP) cefazolin 0.5 g and amikacin 0.025 g four times daily was initiated. After 3 days, her laboratory tests showed a WBC count of 16.5 × 10⁹/L, NEU% of 94.5%, CRP level of 75.6 mg/L, and procalcitonin (PCT) level of 1.4 ng/ml. Analysis of the PD effluent showed turbidity with a WBC count of 4,210/μl (92% NEU). Due to inadequate response, the anti-infection regimen was adjusted to teicoplanin 0.02 g and meropenem 0.25 g (IP).

On day 7, the patient reported no improvement. Laboratory tests indicated a WBC count of 28.3 × 10⁹/L and NEU% of 93.8%. Her CRP was 131 mg/L and PCT was 2.1 ng/ml. Examination of the PD effluent revealed turbidity with a WBC count of 3,260/μl (91% NEU). Both the blood and PD effluent cultures yielded negative results. In light of the unresponsive nature of the treatment, the abdominal dialysis catheter was removed and changed to hemodialysis. Intravenous administration of meropenem and teicoplanin was initiated.

On day 13, with persistent elevation of the infection markers (i.e., CRP and PCT) and suspicion of fungal peritonitis, oral fluconazole 200 mg once daily was initiated and meropenem was discontinued. On day 23, the patient’s WBC count was 13.1 × 10⁹/L, NEU% was 84.1%, CRP was 103 mg/L, and PCT was 1.5 ng/ml. Culture of the PD effluent confirmed the presence of Fusarium spp. by microscopic examination. As a control, the culture of the PD fluid was negative. Teicoplanin and fluconazole were discontinued, and oral voriconazole was commenced with a loading dose of 200 mg on the first day, followed by a maintenance dose of 100 mg every 12 h. After 3 days, given a plasma concentration of voriconazole at 1.38 μg/ml by high-performance liquid chromatography, the maintenance dose was increased to 150 mg in the morning.

On day 37, the patient experienced resolution of abdominal pain. Laboratory analysis revealed a WBC count of 7.79 × 10⁹/L, NEU% of 80.7%, CRP of 64 mg/L, and PCT of 1.7 ng/ml. The plasma concentration of voriconazole measured 2.02 μg/ml. Upon discharge, the patient was prescribed voriconazole at doses of 150 mg in the morning and 100 mg in the evening. At the 2-month post-discharge evaluation, the patient remained afebrile and asymptomatic, with complete normalization of the inflammatory indices, indicating full clinical remission. The alterations in the medication and the key indicators throughout the hospital stay are depicted in Figure 1 .

Fusarium spp. are filamentous fungi that produce mitospores and are ubiquitously present in the environment, inhabiting the air, water, and soil. They are recognized as significant plant pathogens. In humans, they act as opportunistic pathogens, causing localized or disseminated infection after trauma or weakened immunity. The common clinical pathogenic Fusarium species include Fusarium solani, Fusarium verticillioides, Fusarium oxysporum, and Fusarium proliferatum. Among these, F. solani stands out as the most prevalent and virulent species, accounting for approximately 40%–60% of infections. Management of Fusarium infections poses a challenge due to their multidrug resistance and their ability to cause a range of clinical presentations, such as pneumonia, fungemia, cellulitis, and lymphangitis, following skin trauma (Ledoux et al., 2024; Nucci and Anaissie, 2023). Despite these complexities, PD-related Fusarium peritonitis is a rare occurrence, and the available literature on this topic is limited. The Fusarium spp. infection in this case was likely related to her occupation as a farmer and her living environment. Moreover, as a patient with CKD 5 undergoing PD, she is not only repeatedly exposed to this environment during dialysis but is also immunocompromised, further increasing the risk of infection. Regrettably, neither the infecting subspecies nor the antimicrobial susceptibility profile could be determined.

In a multicenter study involving 88 patients with Fusarium infection, an analysis was conducted on the correlation between the minimum inhibitory concentration (MIC) of antifungal agents and the treatment outcomes. The mean MIC₅₀ values of voriconazole against F. solani and F. oxysporum were determined to be 8 and 4 μg/ml, respectively, while those of amphotericin B were 2 and 1 μg/ml, respectively. In a comparative analysis, it was observed that there was no statistically significant variance in the mortality rates between voriconazole and amphotericin B liposomes. Conversely, amphotericin B deoxycholate exhibited a notably elevated mortality rate of 60% (Nucci et al., 2021). In addition, a retrospective multicenter investigation that included 233 instances of invasive Fusarium infection revealed similar 90-day survival rates for voriconazole and amphotericin B liposomes, while amphotericin B deoxycholate demonstrated a distinctly inferior outcome (Nucci et al., 2014). The 2021 Global Guidelines robustly advocate intravenous voriconazole or amphotericin B liposomes, either as monotherapy or in combination, as the primary therapeutic approach. Isavuconazonium or posaconazole is recommended as a second-line treatment. Notably, amphotericin B deoxycholate is not recommended in this context (Hoenigl et al., 2021).

At present, there exists a lack of consensus regarding the optimal management of peritonitis related to Fusarium spp. in patients with PD. Table 1 displays a compilation and summary of the reported cases of Fusarium peritonitis from the references (Bibashi et al., 2002; da Silva-Rocha et al., 2015; Flynn et al., 1996; Garbino et al., 2005; García-Tapia et al., 1999; Gaur et al., 2010; Kerr et al., 1983; Liu and Sun, 2023; Rippon et al., 1988; Shah et al., 2014; Unal et al., 2011; Zhao et al., 2022). For drug selection, liposomal amphotericin B was unavailable, and amphotericin B deoxycholate was excluded due to its pronounced toxicity and poor prognosis. Intravenous voriconazole was withheld to avoid sulfobutyl-ether-β-cyclodextrin accumulation in CKD. Oral voriconazole, with equivalent bioavailability, was used instead and attained effective concentrations. Clinical pharmacists recommended the initial regimen of oral voriconazole for this patient, with a measured plasma concentration of 1.05 μg/ml. However, it is noteworthy that the MIC for Fusarium is relatively elevated. Studies have indicated that the MIC of the commonly obtained voriconazole is at least 2 μg/ml (Espinel-Ingroff et al., 2016), with a maximum of 5 μg/ml (Chen et al., 2018). Therefore, clinical pharmacists recommended an escalation in the voriconazole dosage to 150 mg in the morning. Subsequent monitoring revealed an increase in the plasma concentration to 2.02 μg/ml. This adjusted treatment regimen resulted in a notable alleviation of the patient’s abdominal pain and a substantial decrease in the infection markers.

PD-related peritonitis caused by Fusarium spp. is a rare occurrence. The diagnosis was confirmed for this case due to meeting all three of three diagnostic criteria: abdominal pain and cloudy effluent; effluent WBC count >100 × 10⁶/L (4,460 × 10⁶/L) with >90% NEU; and effluent culture positive for Fusarium spp. However, the pathogen was not cultured until 13 days after admission, which delayed the treatment to some extent. Rapid assays such as the (1→3)-β-d-glucan test, the galactomannan test, and next-generation sequencing of the blood or peritoneal dialysate samples can accelerate the identification of rare fungal peritonitis.

Large-scale investigations focusing on antifungal interventions for Fusarium peritonitis are scarce, with the current therapeutic strategies predominantly documented through isolated case reports. A key limitation is the absence of Fusarium susceptibility data, leaving antifungal selection empirical rather than targeted. Fortunately, in this case, clinical pharmacists conducted a comprehensive review of the pertinent literature, evaluated the epidemiological aspects of Fusarium infections, appraised the pharmacological profiles of therapeutic agents, and collaborated with clinicians to devise personalized antifungal regimens incorporating therapeutic drug monitoring. Finally, despite the eventual recovery, the patient and her family lamented the delayed identification of the pathogen that needlessly prolonged hospitalization. This case underscores the significance of oral voriconazole combined with therapeutic drug monitoring in the management of peritonitis associated with Fusarium in PD and serves as a valuable reference regarding its efficacy.