The efficacy of fluconazole for anti-fungal prophylaxis in peritoneal dialysis patients: A systematic review and meta-analysis / Eficacia de fluconazol para profilaxis antifúngica en los pacientes de diálisis peritoneal: revisión sistemática y metaanálisis

Introduction and objectives: The efficacy of fluconazole as a prophylactic strategy in patients with chronic kidney disease (CKD) on peritoneal dialysis (PD) with prior antibiotic exposure is controversial in the current literature. This study aimed to compare a strategy of fluconazole prophylaxis versus no-prophylaxis for patients in PD on antibiotics for previous episodes of peritonitis. Materials and methods: We performed a systematic review and meta-analysis of observational studies and randomized controlled trials (RCTs) comparing fluconazole prophylaxis with no prophylaxis for PD-related peritonitis. The search was conducted on PubMed, EMBASE, and Cochrane Central in January 23, 2023. The outcome of interest was the occurrence of fungal peritonitis (FP). Results: We included six studies (1 RCT, 5 observational) with 4515 occurrences of peritonitis, of which 1098 (24.8%) received fluconazole prophylaxis in variable doses, whereas 3417 (75.6%) did not receive prophylaxis during peritonitis episodes. Overall, fluconazole prophylaxis was associated with a lower incidence of FP (OR 0.22; 95% CI 0.12–0.41; p<0.001; I2=0%). Subgroup analysis of studies that administered daily doses of fluconazole also demonstrated a reduced incidence of FP in patients who received antifungal prophylaxis (OR 0.31; CI 0.14–0.69; p=0.004; I2=0%). Conclusions: In this meta-analysis of 4515 episodes of PD-related peritonitis, prophylaxis with fluconazole significantly reduced episodes of FP as compared with no antifungal prophylaxis.(AU)

Introducción y objetivos: La eficacia de fluconazol como estrategia profiláctica en los pacientes con enfermedad renal crónica (ERC) sometidos a diálisis peritoneal (DP) con exposición antibiótica previa es controvertida en la literatura actual. El objetivo de este estudio fue comparar la estrategia de profilaxis con fluconazol frente a no profilaxis para los pacientes de DP con régimen antibiótico por episodios previos de peritonitis. Materiales y métodos: Realizamos una revisión sistemática y metaanálisis de estudios observacionales y ensayos controlados aleatorizados (ECA), comparando la profilaxis con fluconazol y la no profilaxis para la peritonitis relacionada con DP. Dicha búsqueda se realizó en PubMed, EMBASE y Cochrane Central el 23 de enero de 2023. El resultado de interés fue la aparición de peritonitis fúngica (PF). Resultados: Incluimos seis estudios (1 ECA, 5 observacionales) con 4.515 episodios de peritonitis, de los cuales 1.098 (24,8%) recibieron profilaxis de fluconazol en dosis variables, mientras que 3.417 (75,6%) no recibieron profilaxis durante los episodios de peritonitis. En general, la profilaxis de fluconazol estuvo asociada a una menor incidencia de PF (OR: 0,22; IC 95%: 0,12-0,41; p<0,001; I2=0%). El análisis de subgrupo de los estudios que administraron dosis diarias de fluconazol también demostró una incidencia reducida de PF en los pacientes que recibieron profilaxis antifúngica (OR: 0,31; IC 95%: 0,14-0,69; p=0,004, I2=0%). Conclusiones: En este metaanálisis de 4.515 episodios de peritonitis relacionada con DP, la profilaxis con fluconazol redujo significativamente los episodios de PF, en comparación con la no profilaxis antifúngica.(AU)

Unusual and complicated peritonitis: Your questions answered.

Effective treatment of infections is a growing challenge owing to antimicrobial resistance. Peritoneal dialysis (PD) patients experience more frequent hospitalisations than the general population and have greater exposure to antibiotics, making them particularly vulnerable to this threat. Over the last decade, we have noted a surge in cases of complicated peritoneal dialysis-associated peritonitis (PD peritonitis) caused by antimicrobial-resistant organisms, including extended-spectrum beta-lactamase (ESBL), AmpC beta-lactamase-producing Enterobacterales, Pseudomonas aeruginosa and fungi. Practitioners must be alert to these organisms, seek early recognition of these resistance patterns and make timely adjustments in order to avoid delay in treatment that may increase risk of PD catheter removal and technique failure. We present a case of successful treatment of ESBL peritonitis, highlight its challenges, while providing guidance on management of other unusual and complicated PD peritonitis.

Serum Galactomannan: A Predictor of Poor Outcomes in Peritoneal Dialysis Patients With Fungal Peritonitis.

Introduction: The potential value of serum galactomannan index (GMI) in monitoring treatment response in patients with fungal peritonitis who are receiving peritoneal dialysis (PD) was assessed in the present study. Methods: The study included all Thailand fungal PD-related infectious complications surveillance (MycoPDICS) DATA study participants who had timely PD catheter removal and availability of both baseline and ≥2 subsequent serum GMI measurements after starting antifungal therapy (if available). Serum GMI was assessed by direct double-sandwich enzyme-linked immunosorbent assay with reference to positive and negative control samples. Comparisons of categorical variables among groups were analyzed by Fisher's exact test for categorical data and the Wilcoxon rank-sum test for continuous variables. Mortality outcomes were analyzed by survival analyses using Kaplan-Meier curves with Log-rank test. Results: Seventy-six (46%) of 166 participants from 21 PD centers between 2018 and 2022 were included. The median age was 58 (50-65) years, and a half of the patients (50%) had type II diabetes. Nineteen (25%) and 57 (75%) episodes were caused by yeast and mold, respectively. Death occurred in 11 (14%) patients at 3 months, and no differences were observed in demographics, laboratories, treatment characteristics, or in baseline serum GMI between those who died and those who survived. Serum GMI progressively declined over the follow-up period after the completion of treatment. Patients who died had significantly higher posttreatment serum GMI levels and were more likely to have positive GMI after treatment. Conclusion: Serum GMI is an excellent biomarker for risk stratification and treatment response monitoring in patients on PD with fungal peritonitis.

Successful treatment of peritonitis caused by Acremonium species without catheter removal: Case report and literature review.

INTRODUCTION: It is a rare case of continuous ambulatory peritoneal dialysis-related peritonitis associated with Acremonium spp infection. CASE PRESENTATION: Symptoms of Acremonium infection peritonitis are hidden and atypical, leucocytes in ascites are moderately elevated, and general bacterial culture difficulty obtains positive results. In this report, a patient with peritoneal dialysis-related peritonitis caused by Acremonium species was successfully treated without catheter removal in our hospital. The organism species was cultured from a catheter and PD effluent fluid. The patient's peritonitis did not relapse within 6 months. CONCLUSIONS: Once a patient on peritoneal dialysis was infected with fungal peritonitis, the outcome was usually to remove the tube and stop peritoneal dialysis. In this case, our experience is that using a catheter-salvage therapy method, we can successfully cure PD-related peritonitis associated with Acremonium sp.

Peritoneal dialysis-associated peritonitis from pauci-septated mold: Life-threatening but curable.

Two cases of PD-associated peritonitis due to Cunninghamella (C. bertholletiae and C. guizhouensis) were reported here with favorable outcomes, albeit presenting with septicemia. Both patients presented with classic features of bacterial peritonitis, cloudy effluent with a neutrophil predominance, followed by fever and septicemia/septic shock. The pathogen species were confirmed and verified by molecular phylogeny using universal and specific fungal primers. All isolations were susceptible/intermediately susceptible to amphotericin B but resistant to other antifungal agents, including triazoles, caspofungin, and terbinafine. Both cases were successfully treated with timely PD catheter removal and antifungal medications for 2-4 weeks.

A Rare Case of Spontaneous Fungal Peritonitis Caused by Candida lusitaniae in a Patient With Necrotizing Pancreatitis.

Candida lusitaniae is a rare cause of peritonitis most commonly associated with peritoneal dialysis patients. Pancreatitis is one possible cause of ascites with a low serum ascites albumin gradient. Herein, we present a case of spontaneous fungal peritonitis caused by Candida lusitaniae in a patient with necrotizing pancreatitis. The patient was treated with antifungal medication, while her pancreatitis was managed endoscopically with necrosectomy. She improved clinically and was discharged in stable condition.

Intractable ascites in a female receiving hemodialysis.

We report a case of a 60-year-old female who presented with intractable ascites 2 months after switching from peritoneal dialysis (PD) to hemodialysis (HD) due to an episode of refractory culture-negative peritonitis (CNP). Abdominal paracentesis yielded inflammatory ascites, which later grew Cladosporium cladosporioides, establishing the diagnosis of fungal peritonitis. She was successfully treated with a 4-week course of oral voriconazole. Cladosporium spp. are common fungi in the environment but rarely cause PD-associated peritonitis and can be challenging to diagnose with conventional microbiologic evaluation. In summary, PD-associated peritonitis can worsen after a patient switches to HD. Therefore, it is essential to maintain a high level of suspicion for such complications related to their previous dialysis modality to arrive at an accurate diagnosis.

A case of Neurospora sitophila causing PD peritonitis.

We describe a rare case of fungal peritoneal dialysis (PD) peritonitis caused by the ascomycete fungus Neurospora sitophila (N. sitophila). The patient had little response to initial antibiotics and PD catheter removal was necessary for source control. The fungal biomarker ß-d-glucan (BDG) was positive prior to N. sitophila being cultured and remained positive for 6 months after discharge. Use of BDG early in the assessment of PD peritonitis may reduce time to definitive therapy in fungal peritonitis.

Clinical Characteristics and Early Diagnosis of Spontaneous Fungal Peritonitis/Fungiascites in Hospitalized Cirrhotic Patients with Ascites: A Case-Control Study.

BACKGROUND: Spontaneous fungal peritonitis (SFP) and fungiascites is less well-recognized and described in patients with liver cirrhosis. The aims of this study were to determine the clinical characteristics, prognosis, and risk factors of cirrhotic patients with SFP/fungiascites and to improve early differential diagnosis with spontaneous bacterial peritonitis (SBP). METHODS: This was a retrospective case-control study of 54 cases of spontaneous peritonitis in cirrhotic patients (52 SFP and 2 fungiascites) with fungus-positive ascitic culture. Fifty-four SBP cirrhotic patients with bacteria-positive ascitic culture were randomly enrolled as a control group. A nomogram was developed for the early differential diagnosis of SFP and fungiascites. RESULTS: Hospital-acquired infection was the main cause of SFP/fungiascites. Of the 54 SFP/fungiascites patients, 31 (57.41%) patients carried on with the antifungal treatment, which seemed to improve short-term (30-days) mortality but not long-term mortality. Septic shock and HCC were independent predictors of high 30-day mortality in SFP/fungiascites patients. We constructed a predictive nomogram model that included AKI/HRS, fever, (1,3)-ß-D-glucan, and hospital-acquired infection markers for early differential diagnosis of SFP/fungiascites in cirrhotic patients with ascites from SBP, and the diagnostic performance was favorable, with an AUC of 0.930 (95% CI: 0.874-0.985). CONCLUSIONS: SFP/fungiascites was associated with high mortality. The nomogram established in this article is a useful tool for identifying SFP/fungiascites in SBP patients early. For patients with strongly suspected or confirmed SFP/fungiascites, timely antifungal therapy should be administered.

Candida nivariensis, an emerging fungus causing peritonitis in a patient receiving peritoneal dialysis.

Fungal peritonitis (FP) is usually associated with poor patient outcomes and is mostly caused by non-albicans Candida species. We present a Candida nivariensis-associated peritonitis in a 68-year-old woman with end-stage kidney disease on peritoneal dialysis (PD). Biochemical profiling of the cultured yeast of the effluent sample did not adequately identify the yeast. Hence, molecular phylogeny and Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) mass spectroscopy were employed which correctly identified the causative species, C. nivariensis. PD catheter was removed and oral fluconazole was promptly started according to the 2022 International Society for PD (ISPD) Peritonitis Guidelines. However, the patient achieved only a partial clinical response and eventually died. The susceptibility test showed that the pathogen was susceptible to amphotericin B and voriconazole but resistant to other triazoles. This report underlines the importance of identifying the species, though rarely reported, and the drug susceptibility of the organism.

Peritonitis after exposure to biocontrol-agent fumes containing Talaromyces flavus: a case report in peritoneal dialysis patient.

BACKGROUND: The first case of Taralomyces flavus infection in human and peritoneal dialysis (PD) patient after exposure to biocontrol agent fumes is reported here. CASE PRESENTATION: A 77-year-old Thai female farmer with kidney failure presented with peritonitis and PD catheter obstruction from fungal biofilms. The potential root cause of infection was associated with exposure to biocontrol-agent fumes containing pathogen during agricultural work in her garden. This source of infection has not been mentioned previously. Showering and changing clothes right after outdoor activity with a high density of fungal matters or dust should be added to the routine aseptic technique before performing PD bag exchange to prevent the system contamination. Although the patient received early treatment with liposomal amphotericin B, itraconazole, and catheter removal, according to the ISPD Guideline 2016 and the Global Guideline 2021, the outcome was unfavorable. Antifungal susceptibility testing later revealed that the pathogen was only susceptible to voriconazole. Thus, antifungal susceptibility should be tested if the patient fails or slowly responds to the primary antifungal regimen. CONCLUSIONS: T. flavus peritonitis is reported here after exposure to biocontrol-agent fumes containing the pathogen. This work also alerts and reiterates nephrology peers to be aware of this overlooked source of peritonitis, the exposure to dusty environments, specifically containing biocontrol-agent fumes.

Peritoneal dialysis-associated peritonitis caused by Exophiala spinifera: A case report and review of literature.

Exophiala spinifera is a black ascomycetous yeast and is responsible for phaeohyphomycosis. We provide the first case report of peritoneal dialysis (PD)-associated peritonitis in a female patient with progressive impairment of visual capacity. The infection was caused by a cutaneous infection of her hands. The patient responded well with PD catheter removal and 2-week antifungal medication. This case emphasizes the importance of hand hygiene and regular eye evaluation in preventing environment-bound infection in patients on PD. 2012 Elsevier Ltd. All rights reserved.

Fungal Peritonitis Associated With Peritoneal Dialysis Due to Non-Albicans Candida: A Case Series.

Fungal peritonitis secondary to non-albicans Candida is reported less frequently. There are uncertainties regarding the treatment of non-albicans Candida infection (i.e., preferred route or initial drug). The objective of this study is to determine the clinical characteristics and treatment used in cases of peritoneal dialysis associated fungal peritonitis secondary to non-albicans Candida. We report four cases with different clinical characteristics and different routes of administration of the antifungal drug, with no deaths. In all four patients, there were risk factors similar to those reported worldwide, without presenting the route of administration of the antifungal drug as a risk factor, suggesting that the mainstay of treatment is early initiation of the antifungal drug and early removal of the catheter.

Fungal Peritonitis Secondary to Aspergillosis in a Peritoneal Dialysis Patient.

Fungal peritonitis remains a serious complication of peritoneal dialysis that carries a high morbidity and mortality. Most cases of fungal infections are due to Candida species; however few cases are seen in the setting of non-Candida such Aspergillus, Fusarium, and Mucor. Prompt peritoneal dialysis catheter removal and early anti-fungal treatment have been considered as best strategies to improve survival. We present a rare case of a 27-year-old male with focal segmental glomerulosclerosis on peritoneal dialysis (PD) presented to the hospital recurrent episodes of abdominal pain, diarrhea, and cloudy output from his peritoneal catheter. He was found to have fungal peritonitis secondary to Aspergillosis Fumigatus. This report highlights that fungal peritonitis should be considered in the differential diagnosis of patients with prolonged antibiotic use, recent bacterial peritonitis, and recent hospitalization. The speciation of Aspergillosis Fumigatus carries a rare incidence in this population and voriconazole is the mainstay treatment.

Phytopathogen transmitted from plant to human causing peritoneal dialysis-associated peritonitis.

We report the first case of peritoneal dialysis (PD)-associated peritonitis due to Sporothrix schenckii, a thermally dimorphic black fungus transmitted from epiphytotic disease. The patient presented with PD-associated peritonitis and fungal colonisation inside the PD catheter's lumen after an exposing 'wet contamination' event with a phytopathogen 11 days prior to the onset of infection. The human pathogen and phytopathogen were confirmed the same species by nucleotide sequences of the internal transcribed spacer and large subunit regions of the ribosomal RNA gene. A 'wet contamination' should be closely monitored for an extended period, and a broader spectrum of organisms might lead to peritonitis, particularly in centres with a high prevalence of fungal infection. PD patients and their caregivers should have periodic retraining of aseptic technique and personnel hygiene. We also recommend a long course of antifungal medication in eradicating peritoneal sporotrichosis to prevent unfavourable outcomes and relapsing peritonitis from this organism.

Characteristics Analysis, Clinical Outcome and Risk Factors for Fungal Peritonitis in Peritoneal Dialysis Patients: A 10-Year Case-Control Study.

Background: Fungal peritonitis (FP) is a rare but severe complication that can appear in patients receiving peritoneal dialysis (PD). This study aimed to investigate the incidence rate and clinical characteristics of FP, evaluate clinical outcomes between FP and bacterial peritonitis (BP) patients on PD, and especially estimate the risk factors for FP outbreak. Methods: All episodes of FP diagnosed in our hospital from January 1, 2011, to December 31, 2020, were reviewed in this single-center study. FP cases were analyzed and compared with patients diagnosed with BP in a 1:6 ratio matching for case-control study. Patient information, including clinical information, biochemical analysis, and outcomes, was recorded. Univariate and multivariate logistic regression model were used to analyze the risk factors for FP. Results: A total of 15 FP episodes were observed in 15 PD patients, with an FP rate of 0.0071 episodes per patient-year. Seventeen strains of fungi were isolated and identified. Candida was the most common pathogen (15 strains, 88.2%), followed by Aspergillus fumigatus (2 strains, 11.8%). Between the groups, FP group showed a higher rate of HD transfer and catheter removal, and a lower rate of PD resumption in the short-term outcome (all P < 0.01), while no significant difference in the mortality was noted during the whole study period. The multivariate logistic regression analysis showed that longer PD duration (odds ratio [OR] 1.042, 95% confidence interval [CI] 1.012-1.073, P < 0.01), higher serum potassium (OR 3.373, 95% CI 1.068-10.649, P < 0.05), elevated estimated glomerular filtration rate (eGFR) (OR 1.845, 95% CI 1.151-2.955, P < 0.05), reduced serum albumin level (OR 0.820, 95% CI 0.695-0.968, P < 0.05) and peritoneal effluent polymorphonuclear (PMN) count (OR 0.940, 95%CI 0.900-0.981, P < 0.01) were significantly increased the risk for FP. Conclusion: These results suggested that FP leads to higher rate of catheter removal and HD transfer, and a lower rate of PD resumption than BP, and that additional attention should be paid to hypoalbuminemia, increased serum potassium, long PD duration, and low peritoneal effluent PMN in PD patients.

Serum potassium, albumin and vitamin B12 as potential oxidative stress markers of fungal peritonitis.

BACKGROUND: Biomarkers of oxidative stress (OS) have been poorly explored in fungal peritonitis (FP). Potassium is a regulator of pro-oxidants and antioxidants. Albumin and vitamin B12 (B12) are vital antioxidant agents in the circulatory system. This study aimed to investigate the antioxidative role of serum potassium, albumin and B12 in FP. METHODS: Serum levels of potassium, albumin and B12 were retrospectively analyzed in 21 patients with a confirmed diagnosis of FP, 105 bacterial peritonitis (BP) patients and 210 patients receiving peritoneal dialysis without peritonitis. RESULTS: Serum levels of potassium, albumin and B12 were lower in FP patients than in BP patients. Serum potassium concentration was statistically related to albumin concentration in peritonitis patients. Univariate and multivariate binary logistic regression analysis suggested that serum level of potassium and albumin were independent risk factors of FP when compared with BP. Lower potassium and B12 levels were independently associated with higher rates of technique failure in peritonitis. CONCLUSION: These findings suggest lower serum potassium, albumin and B12 as potential oxidative stress markers of FP and raise the hypothesis that an increased level of OS could contribute to FP.KEY MESSAGESFP remains a serious complication of peritoneal dialysis (PD), with higher morbidity (1-23.8%) and mortality (2-25%), and oxidative stress plays a role in it.Our study suggested serum potassium, albumin and vitamin B12 as potential oxidative stress markers of fungal peritonitis.

The first human report of Hyphopichia burtonii, initially misdiagnosed as sterile peritonitis in a patient on peritoneal dialysis.

This is the first human infection caused by Hyphopichia burtonii, resulting in peritonitis in a patient on peritoneal dialysis initially diagnosed as sterile peritonitis, resulting in delayed diagnosis and treatment. This pathogen posed a challenging diagnosis, causing low-grade peritonitis and difficulty to culture with standard bacterial broth. Moreover, automated platforms for pathogenic yeast identification could not specify the species, but broad-range PCR targeting rDNA followed by DNA sequencing successfully solved the etiology.

Clinical Features and Risk Factors of Fungal Peritonitis in Children on Peritoneal Dialysis.

Objective: To analyse the clinical manifestations, aetiology, prognosis, and risk factors of fungal peritonitis (FP) in children on peritoneal dialysis (PD). Methods: Among 322 children undergoing PD at Children's Hospital of Fudan University, between January 2001 and December 2019, FP cases were retrospectively analysed and compared with those of bacterial peritonitis (BP) to analyse the risk factors of FP. Results: A total of 124 cases of peritonitis were treated, including 11 FP cases in 11 children (0.0019 episodes/patient*month) and 113 BP cases in 64 children (0.02 episodes/patient*month). Among the 11 FP cases, 7 cases (63.64%) were caused by Candida and Candida parapsilosis (5/7) was the most common pathogen of Candida. All FP patients were converted to haemodialysis (HD) and did not resume PD during follow-up. Two patients (18.2%) died after 6 months of HD due to heart failure, 2 patients underwent kidney transplant after 2 years of infection, and the other 7 patients were still on HD. The univariate analysis showed the usage rate of antibiotics in the month before the onset of peritonitis was higher (45.45 vs. 15.93%) and the mean serum albumin was lower (31.4 vs. 34.4 g/L) in the FP group when compared with BP group (P < 0.05), while multivariate analysis showed that serum albumin ≤ 30 g/L was an independent risk factor for FP (odds ratio 4.896, 95% confidence interval 1.335-17.961). Conclusion: FP is a rare complication of PD in children, but it is associated with high technique failure. Attention should be paid to hypoproteinaemia and antibiotic use in children on PD.