Peritoneal dialysis-associated peritonitis due to infected umbilicus

Abstract

We provide the first case report of peritoneal dialysis (PD)-associated peritonitis due to Lasiodiplodia theobromae, a known plant pathogen causing rotting and dieback in post-harvest citrus fruit, in immunocompetent patient with fungal colonization inside the PD catheter lumen. A root cause analysis suspected the patient's umbilical infection as the source of contamination. The fungal infection was established through microscopic examination of the PD catheter lumen and galactomannan testing in both serum and effluent. The species of pathogen was confirmed by DNA barcoding. The patient responded well to timely PD catheter removal and a 2-week course of oral voriconazole. Preventive strategies should prioritize hygiene practices, including umbilical care, to mitigate the risk of contamination and subsequent infections of fungal pathogens.

1. Introduction

Fungal peritonitis represents a potentially life-threatening complication of chronic peritoneal dialysis (PD), causing high mortality rates [[1], [2], [3], [4]]. Lasiodiplodia theobromae, a plant pathogen responsible for rotting and dieback, uncommonly causes human diseases, primarily affecting the eyes [[5], [6], [7], [8]], sinuses [9] skin [10] and subcutaneous tissue [11]. However, deep-seated infections have been reported in immunocompromised hosts causing osteomyelitis [12] and lung infections in liver transplant patients [13]. Nevertheless, this fungal has never been reported as a cause of peritonitis in PD patients.

1.1. Case presentation

A 60-year-old Thai male, with a history of long-standing hypertension, type 2 diabetes mellitus, and end-stage kidney disease, had been undergoing continuous ambulatory PD (2Lx 4 exchanges daily) for 7 years without any PD-associated infectious complications. He presented to Sukhothai Hospital with generalized abdominal pain, cloudy effluent, and observed multiple black intraluminal colonizations inside his PD catheter lumen (Fig. 1A).

Fig. 1.

Black colonization was observed inside the PD catheter lumen (A); Direct microscopic examination with a 20 % potassium hydroxide (KOH) mount from the catheter revealed dark-brown branching septate hyphae (B). Lasiodiplodia theobromae colonies grown on Sabouraud dextrose agar (Oxoid, Hampshire, UK) on day 3 (C) exhibiting a long, dark septate hyphae when viewed under lactophenol cotton blue mounting (D). The infected umbilicus demonstrated well-demarcated erythematous lesion and scaling (E). (For interpretation of the references to colour in this figure legend, the reader is referred to the Web version of this article.)

On the first day of hospitalization (day 1), the PD effluent (PDE) demonstrated a leukocyte count of 343 cells/mm³ with 84 % neutrophils raising suspicion of bacterial peritonitis. Consequently, empirical treatment with intraperitoneal ceftazidime and cefazolin, 1 gm each, was initiated. By day 5, the PDE leukocyte count remained high at 330 cells/mm³ with neutrophils predominance, and there was no clinical improvement. However, all PDE cultures revealed negative bacteria and fungi growths, leading to the diagnosis of refractory peritonitis. Subsequently, the initial antibiotic regimen was escalated to intraperitoneal meropenem, but due to the lack of clinical improvement, the PD catheter was removed on day 25.

The removed PD transfer set, catheters, serum, and PDE were submitted to a central laboratory for microorganism identification. Direct microscopic examination with 20 % potassium hydroxide (KOH) mount from the catheter's colonization revealed dark-brown branching septate hyphae (Fig. 1B). PDE and serum galactomannan tests were positive, with values of 4.92 (cutoff level ≥0.50) and 0.96 (cutoff level ≥0.56), respectively. The species was identified as L. theobromae using molecular phylogeny, which involved analyzing ribosomal DNA. Specifically, internal transcribed spacer (ITS) regions were examined using ITS1/ITS4 primers regions, along with the small subunit (SSU) utilizing NS1/NS4 primers, and the large subunit (LSU) using LR0R/LR7 and NL1/NL4 primers of the nuclear ribosomal DNA gene complex. The analysis revealed a range of 63–99 % query coverage and 96–100 % identities. The corresponding accession numbers for these sequences are HM466951.2, MN181372.1, MT644474.1, MT372634.1, and MN893998.1.

The patient was promptly prescribed oral voriconazole at 6 mg/kg twice daily on day 30, followed by 4 mg/kg twice daily for 14 days. His symptoms gradually improved, and serum galactomannan converted to negative results. Consequently, the patient was permanently transferred to hemodialysis without relapsing peritonitis.

A root-cause analysis was conducted to ascertain the infection's etiology. The patient reported improper hand washing at times. Well-circumscribed lesions surrounding the umbilicus with erythematous hyperpigmentation and scaling were observed (Fig. 1E). Additionally, he reported a history of contact with rotted citrus fruits and bananas. Skin scrapping was performed and subsequently confirmed the same pathogen identified by culture and PCR (accession number MN893998.1). Touch contamination from his umbilicus was suspected as a potential route of the infection. Hence, emphasis was placed on aseptic technique, skin and umbilicus hygiene, and a 2-week course of topical ketoconazole was applied to the patient's umbilicus. The patient responded well to the above treatment, and the infections were completely resolved.

2. Discussion

This is a case report of PD-associated peritonitis and tinea corporis caused by L. theobromae, with DNA sequencing confirming the presence of the same pathogens in both the infected umbilical skin and dialysate. In the root cause analysis, touch contamination from the patient's umbilicus was suspected as the source of this rare organism.

L. theobromae is a dematiaceous mold belonging to the phylum Ascomycola, Class Dothideomycetes, Order Botryospheariales, and Family Botryosphaeriaceae [14]. It exhibits rapid growth on dextrose agar within the temperature range of 20–30°C, characterized by white to off dark aerial mycelia, and subsequently produces abundant black pigmentation. Primarily identified as a plant pathogen causing rot and dieback in fruits and plants in tropical and subtropical regions [14]. This fungus commonly infects various citrus fruit such as banana, avocados, mangos, papaya, strawberry, and guava after harvest [14]. Human infections are rare, with the first reported case occurring as a cause of human keratomycosis in Bangalore, India, in 1967 [5]. Subsequent case reports have described infections in healthy patients, causing keratitis [8], endophthalmitis [6], corneal abscess [7], sinusitis [9], subcutaneous ulcers [11], multiple skin nodules [10], and onychomycosis [15], while osteomyelitis [12] and pulmonary infection [13] have been reported in immunocompromised hosts and transplant patients.

To our knowledge, this case represents the first report of PD-associated fungal peritonitis caused by this pathogen in immunocompetent host. The clinical manifestation and PDE leukocyte count were similar to bacterial peritonitis, initially leading to maltreatment with antibiotics. Intraluminal colonization and positive PDE and serum galactomannan tests are indicatives of fungal infection with sensitivities 77 % [16], and 65 % [17], respectively. Fungal DNA barcoding employing universal fungal primers (ITS1/ITS4, NS1/NS4, LR0R/LR7, and NL1/NL4) identified and confirmed the species of causative pathogens.

According to the 2022 International Society for PD (ISPD) Peritonitis Guidelines, prompt diagnosis, timely PD catheter removal, and administration of appropriate antifungal medication for a minimum of 2 weeks after PD catheter removal are crucial for the treatment of fungal peritonitis. There are no specific antifungal recommendations for the treatment of L. theobromae in either the 2022 ISPD Guidelines [18] and the 2021 Global guideline for the diagnosis and management of rare mold infections: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology and the American Society for Microbiology [19]. Previous literatures exhibits heterogeneity in treatment regimen, including systemic voriconazole [11,12] and systemic amphotericin B (9). Therefore, based on this case, we recommend voriconazole for the specific treatment of this dematiaceous mold infection.

Peritonitis prevention should be emphasized, especially in cases of touch contamination, as this fungus is commonly found in daily dietary items. Therefore, hand hygiene and maintaining aseptic technique during each step of the PD process are crucial. The umbilicus is prone to retaining moisture due to perspiration and showering, and it often retains unwashed soap and fibers from clothing. Individuals may not consciously wipe or dry the umbilicus specifically. Retained moisture and friction can disrupt the skin barrier, rendering the area more susceptible to fungal colonization and providing an optimal environment for its proliferation. Giving careful attention to the umbilicus while dressing the PD catheter exit site is crucial. Neglecting this step may result in the persistent presence of dermatophytes in the area, serving as a continual source of infection and potentially leading to peritonitis, as demonstrated in our case. While the pathogen was isolated from the umbilical skin lesion in our presented case, it is conceivable that the pathogen was merely colonization.

In conclusion, we report the first case of fungal peritonitis caused by Lasiodiplodia theobromae, suspected to originate from the umbilical infection and incidental contact contamination. This case underscores the importance of hand and personal hygiene in avoiding preventable infections.

CRediT authorship contribution statement

Veerapat Wattanasatja: Writing – review & editing, Writing – original draft, Conceptualization. Jarubut Phisutrattanaporn: Writing – review & editing, Writing – original draft, Conceptualization. Natchaporn Doenphai: Data curation. Sirirat Sirinual: Data curation. Talerngsak Kanjanabuch: Writing – review & editing, Supervision, Funding acquisition, Formal analysis, Conceptualization.

Handling editor: Adilia Warris