2607-9917Bulletin de la Dialyse à Domicile2607-9917RDPLFFrance10.25796/bdd.v7i1.83363IntroductionMaterials and methodsPatient SelectionMicrobiological investigationClinical managementStatistical AnalysisResultsCausative OrganismsExit-Site InfectionOutcome of repeat peritonitis under antibiotic therapyDiscussionConclusionFundingDeclaration of interestsRepeat peritonitis in peritoneal dialysis : A cohort studyhttps://orcid.org/0009-0004-1394-055XHmaidouchNabilMoroccoHmaidouchn@gmail.comMaakoulSara ElFitahHajarOuzeddounNaimahttps://orcid.org/0000-0003-1998-0320BenamarLoubnaIbn Sina University Hospital Center and Mohammed V University of Rabat, Faculty of Medicine and Pharmacy of Rabat, Department of Nephrology Dialysis Kidney Transplantation, Rabat (Morocco)VergerChristian2042024711912420241542024Authors retain copyright2024Nabil Hmaidouch, Sara El Maakoul, Hajar Fitah, Naima Ouzeddoun, Loubna Benamarhttps://creativecommons.org/licenses/by/4.0This work is licensed under a Creative Commons Attribution 4.0 International License.Repeat peritonitis in peritoneal dialysis : A cohort study
Introduction: The understanding of the pathophysiological mechanisms of repeat peritonitis, defined as the occurrence of peritonitis more than 4 weeks after the end of appropriate antibiotic treatment for a previous episode involving the same germ, remains limited.
Methods: We studied the outcomes of 26 episodes of repeat peritonitis between 2006 and 2024 (Repeat Group) and compared them with 23 episodes of relapsing peritonitis (Relapse Group) and 84 episodes of peritonitis preceded by 4 weeks or more by another episode with a different organism (Control Group).
Results: The majority of cases of repeat peritonitis are caused by gram-positive organisms (65.5%), predominantly Staphylococcus aureus (38.5%), whereas most episodes of relapsing peritonitis are culture-negative (69.5%), followed by gram-negative bacilli episodes (17.4%). Exit site infection is significantly associated with PD peritonitis. Gram-positive cocci are responsible for 95.5% of exit site infections, mainly due to Staphylococcus aureus. In the Repeat Group, 14 (66%) patients achieved a primary response, and 10 (47%) of them reached complete cure. After the first episode of repeat peritonitis, 3 (14%) patients had their catheter removed and were transferred to long-term hemodialysis. ; however, the risk of developing relapsing peritonitis was 4.7%, and recurrent peritonitis was 9.5%.
Conclusion: The definition of repeat peritonitis is clear. Despite a favorable outcome with antibiotic treatment, the risk of further episodes of peritonitis remains high, threatening the time on peritoneal dialysis therapy and the life of the patient.
Peritoneal dialysis (PD) associated-peritonitis is the most common and dreadful complication of PD.
Outcomes of peritonitis vary considerably from one country to another, ranging from cure with antibiotics (69.0-80.7%), catheter removal (10.8-20.4%), or mortality (1.8-6.0%)(Szeto, 2011).
On the other hand, mortality related to peritonitis was defined and reported differently in 55% of studies, with a prevalence ranging from 10% to 20%(Szeto, 2011)(Fried & Bernardini, 1996)(Ye & Zhou, 2017-06-05)(Hassan & Murali, 2022-11).
The International Society of Peritoneal Dialysis (ISPD) 2022 recommendations clearly define repeat peritonitis as an episode of peritonitis occurring more than 4 weeks after the end of antibiotic treatment for a previous episode with the same organism. In contrast, relapsing peritonitis is defined as an episode of peritonitis occurring within 4 weeks of the end of appropriate antibiotic treatment for a previous episode with the same organism, or a sterile episode, and a recurrent peritonitis as an episode that occurs within 4 weeks after completion of therapy but with a different organism(Li et al., 2022).
Regardless of the type of peritonitis, the occurrence of new episodes suggests persistence of infection and may be associated with an increased risk of infectious complications; the prognosis will depend on how quickly the cause is identified and treated.
The aim of this study is to identify patients at risk of developing repeat peritonitis, to understand the associated factors and to assess the outcomes in order to prolong the survival of the technique and to lower morbidity and mortality.
Materials and methodsPatient Selection
From the 2006 opening of our PD unit until January 2024, 235 patients were recruited in our unit.
All episodes of PD peritonitis during this period were carefully considered. (Figure 1)
Example caption for this image
Image
Data was collected by reviewing the French Language Peritoneal Dialysis Registry (RDPLF) database, as well as each patient’s hospital records.
According to the ISPD guidelines(Li et al., 2022), PD peritonitis was diagnosed when at least two of the following are present : 1) abdominal pain and/or cloudy dialysis effluent; 2) dialysis effluent white cell count > 100/μL or > 0.1 x 109 /L (after a dwell time of at least 2 h), with > 50% polymorphonuclear leukocytes (PMN); 3) positive dialysis effluent culture.
In this study and according to ISPD guidelines , we defined repeat peritonitis as an episode that occurs more than 4 weeks after completion of therapy of a prior episode with the same organism.
In the 18 years of the study period, 378 episodes of PD peritonitis (in 9 389 patient-months of treatment) were recorded in our unit. 26 episodes (6.8%) were repeat peritonitis. The result is compared with 23 episodes of relapsing peritonitis during the same period (the Relapse Group), and 84 episodes of peritonitis which had been preceded by another episode caused by a different organism 4 weeks to 24 months (the Control Group). We excluded culture-negative and polymicrobial episodes while selecting the control episodes.
The demographic characteristics, underlying medical conditions, previous PD peritonitis, catheter removal, and clinical outcome were also examined.
Microbiological investigation
Bacterial culture of the dialysate fluid was performed on Chapman and/or chocolate agar, and on Cystine–lactose–electrolyte-deficient (CLED) and blood agar.
Clinical management
PD peritonitis episodes were treated according to the standard antibiotic protocol of our center at the time, which was systematically modified over time.
We initially administer Ceftazidime and Cefazolin IP or IV, plus an aminoglycoside. Antibiotic regimens for individual patients were modified when culture results were available, and the peritoneal dialysis effluent was regularly inspected. Antibiotic therapy was continued for a total of 14 days for episodes caused by Staphylococcus coagulase negative and 21 days for episodes caused by gram negative bacillus or Staphylococcus aureus.
Primary response was defined clinically as the resolution of abdominal pain, clarification of dialysate on day 5 with antibiotics alone.
Complete cure was defined as complete resolution of PD peritonitis with antibiotics alone without relapse or recurrence within 4 weeks after completion of treatment. The Tenckhoff catheter was removed only after staff discussion. If the catheter is removed, antibiotics are maintained for an additional two weeks . If reinsertion of a new catheter was contraindicated, we consider it as a technique failure and the patient transferred to long term hemodialysis.
Statistical Analysis
Qualitative variables were expressed as numbers and percentages, and compared using the chi-square test. Quantitative variables were expressed either as the mean ± standard deviation (SD)
if the distribution of the variable was normal, and compared using the t student or ANOVA , or as the median with the interquartile range if the distribution of the variable was asymmetric.
Statistical analyses were performed using Jamovi 2.3.21
Results
In our study, 96 patients were included ,with a sex ratio of 1.4 (M/F), while the mean age was 50 ±17,3 years.
While 79,2% of our patients were on Continuous ambulatory peritoneal dialysis (CAPD), 85.4% were autonomous.
Of all our patients, 21 (Repeat Group) developed a repeat peritonitis, 19 patients (Relapse Group) developed relapsing peritonitis, and 56 patients (Control Group) had an episode of peritonitis which had been preceded 4 weeks to 24 months by another episode caused by a different organism.
The baseline clinical characteristics at the time of PD peritonitis of the patients are summarized in Table I. There is no significant difference in the baseline clinical characteristics between groups.
Baseline characteristics of the patients at the time of PD peritonitis
Repeat
Group
Relapse
Group
Control
Group
Comparing Repeat
and Relapse Groups
Comparing Repeat
and Control Groups
No. of patients
21
19
56
-
-
Sex (men:women)
15:6
8:11
34:22
0,123
0,632
Age (years)
44 ±18
42,6 ±16,8
51,1 ± 16,8
0,692
0,149
Duration of dialysis (months)
39 ± 33,7
26,3 ± 23,3
36,3 ± 27,9
0,179
0,718
Duration from last peritonitis episode (months)
mean ± SD
median (range)
19,9 ± 16,7
19 (7,5-30,5)
13,8 ±16,2
6 (1-26)
16,3 ± 16,5
12 (6-19)
0,432
0,595
No. of previous peritonitis
episode
mean ± SD
median (range)
2,67 ± 1,2
2 (2-3)
3,37 ± 1,61
2 (2-4)
2,15 ± 0,448
2 (2-2.5)
0,134
0,024
Diagnosis, no. of cases (%)
glomerulonephritis
diabetes
hypertension
polycystic
others/unknown
Tubulointerstitial
3 (14,3%)
4 (19%)
3 (14,3%)
2 (9,5%)
6 (28,6%)
3 (14,3%)
6 (31,6%)
5 (26,3%)
0 (0%)
0 (0%)
7 (36,8%)
1 (5,3%)
5 (8,9%)
7 (12,5%)
8 (14,3%)
7 (12,5%)
18 (32,1%)
11 (19,6%)
Charlson’s index score
mean ± SD
median (range)
2,52 ± 0,98
2 (2-3)
2,63 ± 1,01
2 (2-3,5)
2,63 ± 0,906
2 (2-3)
0,727
0,666
Causative Organisms
The microbiological cause of the peritonitis is summarized in Table II.
Microbiological cause of the peritonitis episode
Repeat Group
Relapse Group
Control Group
Gram-positive Cocci (GPC)
Staphylococcus aureus
Coagulase Negative Staphylococcus
other Staphylococcus species
other Streptococcus species
17 (65.5%)
10 (38.5%)
5 (19%)
2 (8%)
0
3 (13%)
2 (8,7%)
0
1 (4,3%)
0
45 (53.7%)
19 (22%)
6 (7%)
19 (22%)
1 (1,2%)
Gram negative Bacilli (GNB)
Escherichia coli
Pseudomonas aeruginosa
Others
9 (34.5%)
4 (15.5%)
3 (11.5%)
2 (7.5%)
4 (17.4%)
0
2 (8,7%)
2 (8,7%)
31 (41%)
8 (9,3%)
5 (6%)
22 (25.5%)
Fungi
0
0
3 (3.5%)
Mycobacterium
0
0
3 (3,5%)
Culture-negative
0
16 (69.5%)
0
Total
26
23
86
There was a significant difference in the distribution of the causative organisms between groups.
Staphylococcus aureus (38.5%) is significantly the germ most frequently involved in repeat peritonitis. Although not significant, Escherichia coli (15.5%) was less frequent in this group. However, no fungi or mycobacteria were identified.
Exit-Site Infection
The microbiological cause of exit site infections in the year preceding the occurrence of peritonitis is summarized in Table IIITable III.
Microbiological cause of the exit site infection
Repeat Group
Relapse Group
Exit site infection per year
1 [0-2.5]
1 [0-4]
Gram-positive Cocci (GPC)
Staphylococcus aureus
Coagulase Negative Staphylococcus
other Staphylococcus species
other Streptococcus species
22 (95.5%)
20 (87%)
2 (8.5%)
0
0
13 (54%)
12 (50%)
1 (4%)
0
0
Gram negative Bacilli (GNB)
Pseudomonas aeruginosa
Enterobacter cloacae
Klebsiella pneumoniae
1 (4.3%)
0
0
1 (4.3%)
11 (45%)
8 (33%)
2 (8%)
1 (4%)
Exit site infection is significantly associated with the occurrence of peritonitis (p < 0.001)
In the Repeat Group, GPC were responsible for 95.5% of exit site infections, mainly due to S. aureus (87% of cases), and only 38% of exit site infections were concomitant with peritonitis (p = 0.769).
Outcome of repeat peritonitis under antibiotic therapy
The main clinical results are shown inFigure 2.
Outcome of repeat peritonitis
Image
After a follow-up of 24 months, primary response was achieved in 14 (66%) patients, 11 of them had a GPC PD peritonitis, and a complete cure was reached in 10 (47%) patients.
We recorded one more episode of repeat peritonitis in 4 (19%) patients over an average period of 9 months, and 2 repeat episodes in one (4.7%) patient after two months of the first episode.
Relapsing peritonitis occurred in only one (4.7%) patient. Recurrent peritonitis occurred in 2 (9.5%) patients.
The PD catheter was removed at the first episode of repeat peritonitis in 3 (14%) patients , two of them because of fungal PD peritonitis co-infection , and one of them because of repeated and concomitant tunnel infection.
Discussion
In our study, only 6.8% of all episodes of PD peritonitis were followed by repeat peritonitis, a lower incidence compared to results reported by other studies(Szeto, 2011)(Reis, 2021-01-30).
Our results showed that the rate of repeat peritonitis due to S. aureus and CNSs was approximately 65.5%, which is significantly higher than other reports(Fahim, 2010)(Szeto, 2009)(Sridevi, n.d.).
Unlike the time duration of PD and the time elapsed since the previous episode, the occurrence of an exit site infection in the previous year was significantly associated with the occurrence of peritonitis.
We observed a significant difference between the type of causative germ for repeat peritonitis and that responsible for relapsing peritonitis, suggesting the need for different therapeutic approaches.
Contrary to general expectations [10] (Thirugnanasambathan, 2012-01-01), we noted that episodes of repeat peritonitis had a higher initial response rate and a lower catheter removal rate , probably due to the generally good response to antibiotics of the causative germ, in contrast to other pathogens in the other groups, notably fungi and mycobacterial episodes, which have a high catheter withdrawal rate, which we have found in previous reports(Szeto, 2009).
From a practical perspective, our results highlight the importance of giving particular attention to episodes of repeat peritonitis. Although initial antibiotic therapy may be effective, there is a significant risk of further episodes, indicating subsequent catheter removal.
Nevertheless, risk factors associated with PD peritonitis, such as hypokalaemia [11], obesity, poor lifestyle, immunosuppression, should be investigated and treated, not forgetting treatment of nasal carriage of Staphylococcus aureus and exit site infections (Al-Hwiesh & Abdul Rahman, 2008)(Abud & Kusumota, 2015).
Gastrointestinal disorders that can cause endogenous infections [14] (Tranaeus & Heimbürger, 1990)must be detected and managed as well, such as diverticulosis. On the other hand, Gastrointestinal and gynecologic procedures carry also a risk of PD peritonitis and may be the source of repeat or relapsing peritonitis. For this reason, the ISPD guidelines recommend appropriate antibiotic prophylaxis before each procedure(Li et al., 2022)(Nadeau-Fredette & Bargman, 2014)(Chan, 2022-03-02). Surprisingly, there is no association between polycystic kidney disease and PD peritonitis according to several studies (Lobbedez & Verger, 2011-07-01)(Portoles et al., 2011-09)(Prischl & Dieplinger, 2005-12).
Finally, as reported in a number of studies, increased vigilance and retraining of medical and nursing staff and patients are mandatory to prevent the occurrence of PD peritonitis(Ljungman & Jensen, 2020-03-02)(López & Fano, 2022-03).
Conclusion
Repeat peritonitis is a specific clinical entity. Although they generally have a satisfactory primary response to antibiotic therapy, they present a substantial risk of developing relapsing, recurrent or even more episodes of repeat peritonitis. Therefore, a local cause must be identified and taken care of, and catheter removal should be considered.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Declaration of interests
No conflict of interest to declare.
ReferencesRepeat Peritonitis in Peritoneal Dialysis: Retrospective Review of 181 Consecutive CasesClin J Am Soc Nephrol CJASNApr;6(4):827–33SzetoC.C.2011Peritonitis influences mortality in peritoneal dialysis patientsJ Am Soc Nephrol JASNOct;7(10):2176–82FriedL.F.BernardiniJ.1996The impact of peritoneal dialysis-related peritonitis on mortality in peritoneal dialysis patientsBMC NephrolYeH.ZhouQ.20170605Association of Peritonitis With Cardiovascular Mortality Over Time in the Peritoneal Dialysis Population: An Australia and New Zealand Dialysis and Transplant Registry StudyKidney Int Rep1;7(11):2388–96HassanH.I.C.MuraliK.202211ISPD peritonitis guideline recommendations: 2022 update on prevention and treatmentPerit Dial Int J Int Soc Perit DialMar;42(2):110–53LiP.K.T.ChowK.M.ChoY.FanS.FigueiredoA.E.HarrisT.2022Repeat and Relapsing Peritonitis Microbiological Trends and Outcomes: A 21-Year Single-Center ExperienceInt J NephrolReisM.20210130Coagulase-negative staphylococcal peritonitis in Australian peritoneal dialysis patients: predictors, treatment and outcomes in 936 casesNephrol Dial Transplant Off Publ Eur Dial Transpl Assoc - Eur Ren AssocOct;25(10):3386–92FahimM.2010Recurrent and relapsing peritonitis: causative organisms and response to treatmentAm J Kidney Dis Off J Natl Kidney FoundOct;54(4):702–10SzetoC.C.2009Staphylococcus aureus peritonitis in Australian peritoneal dialysis patients: predictors, treatment, and outcomes in 503 casesPerit Dial Int J Int Soc Perit DialSrideviG.Repeated peritoneal dialysis-associated peritonitis: a multicenter registry studyAm J Kidney Dis Off J Natl Kidney FoundThirugnanasambathanT.20120101Correction of Hypokalemia in Peritoneal Dialysis Patients May Decrease Peritonitis RiskAm J Kidney Disv;80(5):564–5PirainoB.M.2022Prevention of Staphylococcal Peritonitis in CAPD Patients Combining Ablution and MupirocinSaudi J Kidney Dis TransplantOct;19(5):737Al-HwieshA.K.Abdul RahmanI.S.2008Peritonitis and catheter exit-site infection in patients on peritoneal dialysis at homeRev Lat Am Enfermagem235AbudA.C.F.KusumotaL.20159029902-9Diverticular disease of the colon: a risk factor for peritonitis in continuous peritoneal dialysisNephrol Dial Transplant Off Publ Eur Dial Transpl Assoc - Eur Ren Assoc52TranaeusA.HeimbürgerO.19901417141-7Gastroscopy-Related Peritonitis in Peritoneal Dialysis PatientsPerit Dial Int J Int Soc Perit Dial346Nadeau-FredetteA.C.BargmanJ.M.201466770667-70Risk of peritonitis after gastroscopy in peritoneal dialysis patientsPerit Dial Int J Int Soc Perit DialChanG.C.K.20220302Peritoneal dialysis in polycystic kidney disease patients. Report from the French peritoneal dialysis registry (RDPLFNephrol Dial TransplantLobbedezT.VergerC.20110701Peritoneal Dialysis for Patients With Polycystic Kidney Disease in SpainAm J Kidney Dis1;58(3):493PortolesJ.M.TatoA.M.López-SánchezP.201109Peritonealdialyse bei Patienten mit Polyzystischer NierendegenerationWien Klin Wochenschr1;117(6):24–8PrischlF.C.DieplingerG.200512Retraining for prevention of peritonitis in peritoneal dialysis patients: A randomized controlled trialPerit Dial Int J Int Soc Perit DialLjungmanS.JensenJ.E.20200302A retraining program reduces the rate of peritonitis in peritoneal dialysisNefrol Engl Ed1;42(2):219–20LópezA.S.FanoB.L.202203