ARTÍCULO ORIGINAL

Peritoneal dialysis related peritonitis; a single center results

Peritonitis relacionada con la diálisis peritoneal; resultados de un solo centro

Özgül Özbek¹, Hakan Akdam¹, Selcen Öncü², Yavuz Yeniçerioğlu¹, Serkan Öncü³

1) Aydın Adnan Menderes University, Faculty of Medicine, Division of Nephrology, Aydın, Turquía. akdamhakan@yahoo.com
2) Aydın Adnan Menderes University, Faculty of Medicine, Department of Medical Education, Aydın, Turquía
3) Aydın Adnan Menderes University, Faculty of Medicine, Department of Infectious Diseases and Clinical Microbiology, Aydın, Turquía

Recibido en su forma original: 15 de marzo de 2021
Aceptación final: 19 de julio de 2021

Cómo citar este artículo (How to cite this article): Ö. Özbek, H. Akdam, S. Öncü, et al. Peritoneal dialysis related peritonitis; a single center results. Rev Nefrol Dial Traspl. 2022;42(3)206-214

INTRODUCTION
Peritoneal dialysis (PD) is a method of renal replacement therapy used by approximately 200,000 patients worldwide.⁽¹⁾ All dialysis treatments in end stage renal disease patients involve a certain risk of infection due to reduced immune defense and increased potential for microbial contamination related to dialysis techniques.^(2-4) Peritonitis is the most common type of infection associated with PD treatment. PD-related infectious complications may result in significant morbidity such as hospitalization, dialysis failure, catheter loss, sclerosing encapsulating peritonitis, severe pain, and poor patient comfort. Additionally, peritonitis may cause transition to hemodialysis and mortality even though the incidence has gradually decreased with the development of secure attachment systems (Y-connector, twin bag system) in the last 3 decades.^(4-5) Although peritonitis episodes improve rapidly with appropriate treatment, approximately 5% of peritonitis result in death and 15-18% of PD patients die due to peritonitis.^(3-4)
While the incidence of peritonitis was 3.54 per patient-year before 1980, today the worldwide incidence has declined to approximately 0.7-0.9%.(6-7) Advanced age, concomitant disease, cultural, social, environmental and financial factors, educational status, poverty, diabetes, catheter type, modality, has been reported as factors affecting the incidence.^(4-5) Peritonitis remains the most serious complication and the most important cause of technical failure. We aimed to evaluate 10-year peritonitis rate, causative microorganism, clinical outcome, and mortality in PD patients’ follow-up in our unit.

MATERIAL AND METHODS
Patients who were on PD treatment program in our Nephrology Clinic and had peritonitis episode between 1 January 2009 and 31 December 2018 were analyzed retrospectively. The diagnosis of peritonitis was made in the presence of two of the following three criteria.⁽⁸⁾
1) Abdominal pain and/or cloudy peritoneal effluent.
2) After a dwell time of at least 2 hours’ peritoneal effluent leukocyte count >100/mm3 with >50% polymorphonuclear
3) Positive peritoneal effluent culture
The definition of relapsing, recurrent and repeat peritonitis was made according to the “ISPD Peritonitis Recommendations: 2016 Update on Prevention and Treatment” guidelines.⁽⁸⁾

Clinical and laboratory monitoring
Patients demographic, clinical and laboratory findings were obtained from the hospital records. Body mass index, blood pressure, complaints, residual urine amount, PD modality, chronic kidney disease etiology and gender data were recorded.
Bedside dialysate blood culture bottles culture results at the admission of peritonitis episode were evaluated, causative microorganism and culture antibiograms were noted.
Patients’ peritoneal effluent cell counts, hemogram, C-reactive protein, total protein, and albumin test results were evaluated at the baseline (0th day) and 3rd day of the peritonitis episode. Peritoneal catheter removal and deaths due to PD-related peritonitis during hospitalization were noted. Peritonitis rate was calculated by dividing episodes of peritonitis per year by the number of patient-years at risk. Relapsing peritonitis were excluded in the calculation.

Ethics committee approval
Ethics committee approval was obtained from the local ethics committee, dated 12.09.2018 and numbered 53043469-050.04.04. Informed consent was not obtained due to the retrospective nature of the study. This study was conducted in accordance with the ethical standards of the World Medical Association Declaration of Helsinki.

Statistical analysis
Statistical analysis was performed using the Statistical Package for Windows version 18 [SPSS Inc; Chicago, IL, USA] packet program. Data normality was evaluated with Kolmogorov-Smirnov Test. Categorical data shown as number (percentage) and Chi-Square Test was used for analysis. Qualitative variables were shown as mean ± standard deviation or median with 25th - 75th percentile. Student’s t-test and Mann-Whitney U test were used for normal and abnormal distributions, respectively. Binary Logistic Regression Analysis was used to determine independent risk factors. P=<0.05 was considered statistically significant.

RESULTS
A total of 85 peritonitis episodes were detected during 10-year follow-up. Five of them were relapsing peritonitis, one of recurrent peritonitis and one of repeat peritonitis. Relapsing peritonitis were excluded, in the remaining 80 peritonitis episodes, the mean age was 56.18±12.98, 26 (32.5%) cases were female, diabetes mellitus was the most common cause of chronic kidney disease, 31.2% (n=25) of them were on Continuous Ambulatory Peritoneal Dialysis (CAPD) and 68.8% (n=55) of them were on Automated Peritoneal Dialysis (APD). At the admission, all the patients had symptoms of cloudy effluent; abdominal pain was seen in 93.8%, nausea in 65% and fever in 30%.
Age, blood pressure, urine amount, PD modality were similar between genders. On the other hand, 65.4% of female patients were performing PD with their family caregivers, and 11.1% of male patients were performing PD with their family caregivers, the difference was significant (p<0.001).
A total of follow-up duration was 3289 months. The 10-year mean peritonitis rate was 0.29 episode/year. Annually, peritonitis rate was the lowest with 0.14 episode/year in 2016 and the highest with 0.53 episode/year in 2009. (Table 1)

Table 1. Annual peritonitis rate results

The most common causative microorganism was Coagulase Negative Staphylococcus (CoNS). Additionally, 58.8% gram-positive, 21.3% gram-negative, 1.3% fungal infection was detected. Culture negative peritonitis rate was 18.8%. (Figure 1)
68% gram-positive and 12% gram-negative bacteria were detected in CAPD patients, 54.5% gram-positive and 25.5% gram-negative bacteria were detected in APD patients. No significant difference found between the modality of PD and gram staining (p=0.675).
It was found that 63.6% of Streptococcus spp were penicillin sensitive, 62.5% of CoNS were methicillin sensitive, 37.5% were methicillin resistant, and 100% of Staphylococcus aureus were methicillin sensitive.

Figure 1. Causative microorganisms of peritoneal dialysis related peritonitis

Initial clinical and laboratory parameters of the patients were compared according to their bacterial growth in peritoneal effluent as gram-positive or gram-negative bacteria. Peritoneal effluent leukocyte counts were significantly higher in the patient group with gram-negative. Gender, age, body mass index, C-reactive protein, albumin, protein results was not different between gram-positive and negative groups. (Table 2)

Table 2. Baseline values of patients with gram positive and negative strains

(BP: Blood Pressure; PE-DME: Peritoneal Effluent Direct Microscopic Examination; PE-HTA: Peritoneal Effluent Hemogram Tube Analysis)

Peritoneal catheter was removed in 21 (26.25%) of 80 peritonitis episode. Peritonitis divided as: Catheter Removed (n=21) and Catheter not Removed (n=59) group. The catheter was removed in 42.3% of female patients and 18.5% of male patients, the difference was significant (p=0.024). Leukocytes (p<0.001) and neutrophils (p<0.001) count in the 3rd day of peritoneal effluent direct examination, peritoneal effluent leukocytes count in the hemogram tube on the 3rd day (p= 0.011), the levels of C-reactive protein 0th (p=0.008) and 3rd (p=0.010) day were significantly higher in Catheter Removed group. Total protein and albumin levels were significantly higher on day 0 and day 3 in Catheter not Removed group. The catheter was removed in 19.1% of gram-positive peritonitis, 47.1% of gram-negative peritonitis (p<0.026). (Table 3)

Table 3. Comparison of patients with catheter removed and not removed

BP: Blood Pressure; PE-DME: Peritoneal Effluent Direct Microscopic Examination; PE-HTA: Peritoneal Effluent Hemogram Tube Analysis

In the analysis with Binary Logistic Regression, it was found that a decrease in serum albumin value of 1 g/dL increased the probability of removal of the catheter 13.8 fold (95% CI; 2.345-81.339), and in female gender catheter removal risk was 5.1 fold higher, while 0th day C-Reactive Protein and blood leukocytes count variables lost their significance in the model. (Table 4)
Five patients died due to PD-related peritonitis and the mortality rate was 6.25%. All of them were in the catheter removed group. There was no dominant microorganism in patients who died. The microorganism was different in each case; CoNS, Pseudomonas Aeruginosa, Acinetobacter Baumannii, extended-spectrum β-lactamase-producing Escherichia coli, Corynebacterium Spp were determined. Each case died due to peritonitis related septicemia within three weeks after a period of catheter removal and transfer to hemodialysis.

Table 4. Logistic regression analysis of catheter removal

DISCUSSION
Despite current knowledge and technological advances, morbidity and mortality rates in dialysis patients are still high. The mortality risk of dialysis patients is 10 to 30 fold higher than the society.^(9,10) The first 2-year mortality rates of PD patients are approximately 48% lower than hemodialysis patients.⁽¹¹⁾ Furthermore, PD-related peritonitis is one of the main causes of morbidity and mortality. Peritonitis rates can vary widely between individual patients, centers, regions, and countries. 0.63 in Brazil,⁽¹²⁾ 0.37 in Argentina,⁽¹³⁾ 0.18 in Turkey,⁽¹⁴⁾ and 0.16 episode/year in China⁽¹⁵⁾ have been reported. It was stated that the peritonitis rate should not exceed 0.5 episode/year in PD centers.⁽⁸⁾ In our center, overall peritonitis rates during the 10-year was 0.24 episode/year, ranging from 0.14 to 0.53.
Studies showed either superior or similar peritonitis rate of APD in comparison with CAPD.^(16-17) However, most of them were observational rather than randomized studies with a low number of cases. In our study, peritonitis rates were equal between two modalities. It has been suggested that the selection peritoneal dialysis modality should not be based on the risk of peritonitis.⁽⁸⁾
The most common causative microorganisms for PD-related peritonitis are gram-positive bacteria, and CoNS is the most frequent agent.^{(5, 18)} Gram-positive and CoNS bacteria are account between 60-70% and 30-40%, respectively.^{(3, 4, 15, 18)} It has been stated that the skin flora is the reason for gram-positive strains are dominant due to touch contamination during exchange.^(5,18) Gram-negative enteric bacteria are detected at a rate of 10-25%, with the highest rate reported in Asia and Australia.^{(4, 13)} Gram-negative percentage shows increased due to use of mupirocin in the exit site, and recent antibiotic application is a risk factor for gram-negative enteric peritonitis.⁽⁵⁾ Lipopolysaccharide found in gram-negative bacteria increases leukocyte-endothelial interaction and creates a strong inflammatory response, cytokine release is 2-13 fold higher, and these patients have been reported to have more severe clinical signs and symptoms of peritonitis.⁽¹⁹⁾ In our results, peritoneal effluent leukocyte and blood leukocyte counts were significantly higher at the time of admission. These findings may help foresight gram-negative peritonitis.
Microorganism isolation rates may be low in peritoneal effluent culture. Planting in blood culture bottles is recommended to increase the rate of growth in culture.^{(4, 8, 20)} It has been reported that the automatic BACTEC culture technique increased the positive culture rate in patients with peritonitis from 73.55% to 96.55% compared to the manual technique.⁽¹³⁾ In publications, the rate of culture negative peritonitis ranges from 15.9% to 32.1%.^{(13, 21-22)} Our, culture negative peritonitis rate was 18.8%. Culture negative peritonitis rate should be less than 20% and it is recommended to review and improve the sampling and culture methods of the center if the rate was more than 15%^.(8)
It is very important that centers know and follow antibiotic resistance rates, in the regulation of empirical treatment and in preventing the development of resistant organisms. Recent hospitalization and antibiotic therapy could increase the development of methicillin-resistant strains. Gram-positive methicillin-resistant strains increased over the three decades and methicillin-resistant CoNS was approximately 50%.^{(4, 23)} Similarly, in this study the rate of methicillin-resistant CoNS was 37.5%, while no methicillin-resistant Staphylococcus Aureus strain was detected. Empirical antibiotic selection should be determined by the prevalence and types of resistant bacterial isolates, and vancomycin should be preferred at high methicillin resistance rate.⁽⁸⁾
Most of the PD-related peritonitis responds to antibiotic therapy, but a significant proportion of them may require surgical removal of the peritoneal catheter to eradicate the infection. In parallel with our study, catheter removal rates due to peritonitis have been reported in the range of 16-18% and were significantly higher in gram-negative peritonitis.^(7,21) Advanced age, recurrent peritonitis, admission longer than 48 hours, paralytic ileus, hypotension, hypoalbuminemia (<3 g/dL), and causative microorganism such as Escherichia Coli, Enterobacter spp and Pseudomonas spp are important risk factors for catheter removal.^(24-25) Although the relationship of hypoalbuminemia with technical failure is not clear, its low level is a marker of inflammation, malnutrition, and co-morbidity. Albumin synthesis is suppressed in the presence of infection and inflammation, and normal loss of 4-5 g/day increases 3-4 fold during peritonitis.^(26-27) In our study, C-reactive protein, leukocyte and neutrophil were significantly higher in catheter removed group. In addition, serum albumin level was significantly lower in catheter removed group and the level of albumin could be determinant in predicting the catheter removal.
No death was observed in peritonitis cases responding to medical treatment, and the mortality rate in catheter removed patients was 8.9%,⁽²⁵⁾ and the cumulative mortality was seen in less than 4%.⁽⁸⁾ Our cumulative mortality rate was close to previous studies with a rate of 6.25%, while there was no death in catheter not removed.
In conclusion, peritonitis rate may differ even among centers, determining risk factors for each center is of particular importance. Catheter removal was slightly increased at our center. Catheter loss was associated with female gender, gram negative strains and hypoalbuminemia in PD-related peritonitis. Patients should be closely monitored, and necessary precautions should be taken to prevent development of peritonitis and complications.

Conflict of interest: None

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