A retrospective study of patients with Stenotrophomonas maltophilia peritonitis undergoing peritoneal dialysis
Renal Replacement Therapy volume 9, Article number: 18 (2023)
Stenotrophomonas maltophilia (S. maltophilia) is being increasingly recognized as an important cause of nosocomial infections, particularly in immunocompromised patients, such as patients undergoing dialysis. S. maltophilia peritonitis is strongly associated with the loss of peritoneal catheter among patients undergoing peritoneal dialysis (PD) owing to its resistance to different groups of antibiotics. Thus, the aim of this study was to investigate the characteristics of and risk factors for S. maltophilia peritonitis in patients undergoing PD.
This single-center, retrospective, case–control study was conducted between April 2013 and October 2022. Patients who were undergoing PD at Kawashima Hospital and were diagnosed with S. maltophilia peritonitis were included in this study. Controls were randomly selected from among patients who were undergoing PD and were diagnosed with peritonitis caused by microorganisms other than S. maltophilia. The demographic data, clinical characteristics, and initial treatment data of the patients were analyzed to determine the risk factors for PD-related S. maltophilia peritonitis.
Five patients with S. maltophilia peritonitis and 15 controls (three controls to one case) were included in this study. The incidence of S. maltophilia peritonitis was significantly more frequent among patients with diabetes mellitus (80.0% vs. 20.0%; p = 0.031) and among patients with higher white blood cell counts in the dialysate after appropriate antibiotic therapy (2561/µL [349–4654/µL] vs. 20/µL [20–23/µL]; p = 0.0006) than among the control patients. Although all the patients were treated with appropriate antibiotics after the identification of S. maltophilia, they had a significantly higher rate of catheter removal than the controls (80.0% vs. 0.0%; p = 0.001).
Diabetes mellitus may be an important risk factor for S. maltophilia peritonitis in patients undergoing PD.
Stenotrophomonas maltophilia (S. maltophilia) is an aerobic, gram-negative organism with intrinsic multi-drug resistance. S. maltophilia is being increasingly recognized as an important cause of nosocomial infections, particularly in immunocompromised patients . Clinical manifestations of S. maltophilia infection include bacteremia, endocarditis, respiratory infections, urinary tract infections, and peritonitis . Patients undergoing dialysis are ideal targets for infections because they are immunosuppressed. In addition, the prosthetic grafts and central venous or peritoneal catheters required for dialysis can serve as artificial access points for infectious organisms. Peritoneal dialysis (PD)-related peritonitis is a major cause of hospitalization and catheter removal or hemodialysis transfer in patients undergoing PD . S. maltophilia peritonitis is a rare complication of PD that may result in mortality or catheter loss . However, to our knowledge, there is no case series on S. maltophilia peritonitis among patients in Japan. Therefore, the aim of this study was to examine the characteristics of and risk factors for peritonitis caused by S. maltophilia in patients undergoing PD.
This was a single-center, retrospective, case–control study that aimed to investigate the risk factors for PD-related peritonitis, particularly peritonitis caused by S. maltophilia. We retrospectively selected cases of peritonitis caused by S. maltophilia in patients who underwent PD between April 2013 and October 2022 at our institution. S. maltophilia peritonitis was defined as the presence of characteristic clinical features, including peritonitis, dialysate leukocytosis (white blood cell count > 100/µL with neutrophil count > 50%), and growth of S. maltophilia in the dialysate culture. Controls were randomly selected from among patients who underwent PD during the same period and were diagnosed with peritonitis caused by microorganisms other than S. maltophilia, i.e., their dialysate cultures showed growth of microorganisms other than S. maltophilia. Fifteen controls were matched to each case as far as possible for age and sex on a 3:1 basis.
Clinical data, including sex, age, duration of dialysis, number of previous peritonitis episodes, microorganisms in dialysate cultures, presence of diabetes mellitus and cardiovascular disease, body temperature, blood pressure, and laboratory data at the time of the hospital visit were collected by reviewing the patients’ medical records. Laboratory data included white blood cell and platelet counts; hemoglobin, urea nitrogen, creatinine, total protein, serum albumin, serum aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, sodium, potassium, corrected calcium, phosphate, β2-microglobulin, and C-reactive protein levels and dialysate white blood cell counts.
Data were expressed as mean ± standard deviation or median (interquartile range), as appropriate. Categorical variables were evaluated using Fisher’s exact test, whereas continuous variables were compared using Student’s t-test or Mann–Whitney U test, as appropriate. All analyses were performed using JMP, version 16 (SAS Institute Inc., Cary, NC, USA). p < 0.05 was considered statistically significant.
Demographic and clinical characteristics of the patients
A total of 372 peritonitis cases were recorded during the study period. Among these, five were caused by S. maltophilia, accounting for approximately 1.3% of all the peritonitis cases. Thus, five patients with S. maltophilia peritonitis who were undergoing PD were included in the analysis. Fifteen controls (three controls to one case) were included as well. The baseline demographic and clinical characteristics of the five patients are listed in Table 1. The mean age of the patients was 66 years, and four were male. The primary cause of end-stage renal disease in four of the five patients was diabetic nephropathy. None of the patients had any concomitant exit site or tunnel infection. S. maltophilia and Enterococcus faecalis (E. faecalis) were isolated from the dialysate culture of one of the patients, indicating that the patient had a polymicrobial infection. The courses of antibiotic treatment and outcomes are listed in Table 1. After identification of the causative organism in each case, all the patients were properly treated using antibiotics that are sensitive to S. maltophilia. However, the peritoneal effluent of four patients did not clear up, resulting in the removal of their peritoneal catheters.
Clinical and laboratory characteristics of the patients and controls
Table 2 shows the results of the case–control analysis. The rate of peritonitis caused by S. maltophilia was significantly higher among patients with diabetes mellitus (80.0% vs. 20.0%; p = 0.031) and among patients with higher dialysate cell counts after appropriate antibiotic therapy (2561/µL [349–4654/µL] vs. 20/µL [20–23/µL]; p = 0.0006) than among the control patients. In addition, the rate of catheter removal among the patients was significantly higher than that among the controls (80.0% vs. 0%; p = 0.001). However, there were no significant differences in other characteristics between the patients and controls.
Antimicrobial susceptibility of S. maltophilia
The antimicrobial susceptibility profile of S. maltophilia in each case is presented in Table 3. S. maltophilia was susceptible to ceftazidime, minocycline, levofloxacin, and ofloxacin in all cases.
We examined the characteristics of S. maltophilia peritonitis in patients undergoing PD. The results revealed a relationship between diabetes mellitus and S. maltophilia peritonitis in patients undergoing PD. Use of broad-spectrum antibiotics, immunosuppressive therapy, prolonged hospitalization, malignant lesions, and central venous catheterization are considered risk factors for S. maltophilia infection [1, 3]. In the present study, all the five patients with S. maltophilia peritonitis did not have these predisposing conditions. Diabetes mellitus has also been reported to be a predisposing factor for S. maltophilia peritonitis in a previous study . However, all the five patients with S. maltophilia peritonitis included in that study had diabetes mellitus; therefore, their results were not sufficient to conclude that diabetes mellitus is a predisposing factor for S. maltophilia peritonitis.
S. maltophilia is an uncommon pathogen of PD-related peritonitis. Very few case–control studies of S. maltophilia peritonitis have been conducted [3, 4]. The authors of these previous studies reported that the patients with S. maltophilia peritonitis were younger, more likely to be on immunosuppressive therapy, and had lower hemoglobin levels than controls. The present study is the first to show that diabetes mellitus could be a predisposing factor for S. maltophilia peritonitis. This is particularly noteworthy because we compared patients with S. maltophilia with those with peritonitis caused by microorganisms other than S. maltophilia. Patients undergoing PD, especially those with diabetic nephropathy, are more likely to have multifactorial immune defects associated with uremia and other comorbidities, such as diabetes [5, 6], which may lead to S. maltophilia peritonitis.
The rate of S. maltophilia peritonitis at our institution is approximately 1.3%, which is similar to the rates reported in previous studies . A review of the literature (extracted from PubMed) on S. maltophilia peritonitis in patients undergoing PD is summarized in Table 4 [3, 4, 7,8,9,10,11,12,13,14]. Although for approximately half of the patients in these studies there was no information on primary kidney disease, it can be concluded that patients undergoing PD who have S. maltophilia peritonitis tend to have diabetes. The total rate of catheter removal in these studies was 60.6% (20 out of 33 cases). Although all the patients in the present study received appropriate antibiotic therapy after the identification of S. maltophilia, the rate of catheter removal among the patients was significantly higher than that among the controls.
S. maltophilia is usually resistant to many classes of antibiotics, such as cephalosporins, carbapenems, and aminoglycosides . The main mechanism underlying the resistance of S. maltophilia to antibiotics is the presence of gene-encoding efflux pumps and antibiotic-inactivating enzymes . The International Society for Peritoneal Dialysis (ISPD) peritonitis guidelines recommend that S. maltophilia peritonitis be treated with two different classes of antibiotics for at least 3 weeks, with one of the antibiotics being trimethoprim–sulfamethoxazole . Most cases of successful treatment of S. maltophilia peritonitis involve a combination of therapy with different antibacterial drugs (Table 4). In our cohort, only one patient, treated in accordance with the ISPD peritonitis guidelines, could continue PD. In addition to antibiotic resistance, S. maltophilia forms a biofilm on the host surface . Infections caused by biofilm-producing bacteria are difficult to treat and eradicate because they rarely respond to conventional antibiotic treatments. Therefore, peritoneal catheters should be removed early in cases of failure to respond to treatment . S. maltophilia is frequently accompanied by gram-positive bacteria, mainly E. faecalis . S. maltophilia and E. faecalis were both isolated from the dialysate culture of one of the patients in the present study. Therefore, clinicians should always keep in mind that S. maltophilia may not be the only pathogen involved in peritonitis. The ISPD peritonitis guidelines recommended cefazolin plus ceftazidime or cefepime monotherapy as an empiric treatment . Because S. maltophilia is sensitive to ceftazidime, this empiric treatment may improve the clinical outcomes of patients with S. maltophilia peritonitis.
The main limitation of this study is that it was a single-center retrospective study with a small sample size, which may have concealed clinically significant differences between the patients and the controls. Therefore, further multicenter prospective studies are needed to confirm the findings of this study.
Diabetes mellitus may be an important risk factor for S. maltophilia peritonitis in patients undergoing PD.
Availability of data and materials
All data generated or analyzed during this study are included in this published article.
International Society for Peritoneal Dialysis
Looney WJ, Narita M, Mühlemann K. Stenotrophomonas maltophilia: an emerging opportunist human pathogen. Lancet Infect Dis. 2009;9(5):312–23.
Higuchi C, Ito M, Masakane I, Sakura H. Peritonitis in peritoneal dialysis patients in Japan: a 2013 retrospective questionnaire survey of Japanese Society for Peritoneal Dialysis member institutions. Ren Replace Ther. 2016;2(2):1–8.
Taylor G, McKenzie M, Buchanan-Chell M, Perry D, Chui L, Dasgupta M. Peritonitis due to Stenotrophomonas maltophilia in patients undergoing chronic peritoneal dialysis. Perit Dial Int. 1999;19(3):259–62.
Baek JE, Jung EY, Kim HJ, Lee GW, Hahm JR, Kang KR, et al. Stenotrophomonas maltophilia infection in patients receiving continuous ambulatory peritoneal dialysis. Korean J Intern Med. 2004;19(2):104–8.
Pichler R, Afkarian M, Dieter BP, Tuttle KR. Immunity and inflammation in diabetic kidney disease: translating mechanisms to biomarkers and treatment targets. Am J Physiol Ren Physiol. 2017;312(4):F716–31.
Cohen G. Immune dysfunction in uremia 2020. Toxins. 2020;12(7):439.
Szeto CC, Li PK, Leung CB, Yu AW, Lui SF, Lai KN. Xanthomonas maltophilia peritonitis in uremic patients receiving continuous ambulatory peritoneal dialysis. Am J Kidney Dis. 1997;29(1):91–5.
Al-Hilali N, Nampoory MR, Johny KV, Chugh TD. Xanthomonas maltophilia infection in chronic peritoneal dialysis patients. Scand J Urol Nephrol. 2000;34(1):67–9.
Cheng VC, Lo WK, Woo PC, Chan SB, Cheng SW, Ho M, et al. Polymicrobial outbreak of intermittent peritoneal dialysis peritonitis during external wall renovation at a dialysis center. Perit Dial Int. 2001;21(3):296–301.
Tzanetou K, Triantaphillis G, Tsoutsos D, Petropoulou D, Ganteris G, Malamou-Lada E, et al. Stenotrophomonas maltophilia peritonitis in CAPD patients: susceptibility to antibiotics and treatment outcome: a report of five cases. Perit Dial Int. 2004;24(4):401–4.
Machuca E, Ortiz AM, Rabagliati R. Stenotrophomonas maltophilia peritonitis in a patient receiving automated peritoneal dialysis. Adv Perit Dial. 2005;21:63–5.
Lee YK, Kim JK, Oh SE, Lee J, Noh JW. Successful antibiotic lock therapy in patients with refractory peritonitis. Clin Nephrol. 2009;72(6):488–91.
Azak A, Kocak G, Huddam B, Iscan G, Duranay M. An unusual cause of continuous ambulatory peritoneal dialysis-associated outpatient peritonitis: Stenotrophomonas maltophilia. Am J Infect Control. 2011;39(7):618.
Millán-Díaz B, González-Tabarés L, Cobelo-Casas C, López-Vázquez M, Calviño-Varela J. Stenotrophomonas maltophilia: a rare cause of peritonitis in CAPD patients. Nefrología (English Edition). 2017;37(6):646–7.
Gil-Gil T, Martínez JL, Blanco P. Mechanisms of antimicrobial resistance in Stenotrophomonas maltophilia: a review of current knowledge. Expert Rev Anti Infect Ther. 2020;18(4):335–47.
Li PK, Chow KM, Cho Y, Fan S, Figueiredo AE, Harris T, et al. ISPD peritonitis guideline recommendations: 2022 update on prevention and treatment. Perit Dial Int. 2022;42(2):110–53.
García G, Girón JA, Yañez JA, Cedillo ML. Stenotrophomonas maltophilia and its ability to form biofilms. Microbiol Res. 2022;14(1):1–20.
Wakino S, Imai E, Yoshioka K, Kamayachi T, Minakuchi H, Hayashi K, et al. Clinical importance of Stenotrophomonas maltophilia nosocomial pneumonia due to its high mortality in hemodialysis patients. Ther Apher Dial. 2009;13(3):193–8.
We thank Editage for technical assistance in editing the early draft of this manuscript.
Ethics approval and consent to participate
This study was approved by the Ethical Committee of Kawashima Hospital (approval no. 1119) and was conducted in accordance with the principles of the Declaration of Helsinki and Japanese ethical guidelines. All patients granted informed consent for their data to be included in this study.
Consent for publication
The authors declare that they have no competing interests.
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Shima, H., Okamoto, T., Tashiro, M. et al. A retrospective study of patients with Stenotrophomonas maltophilia peritonitis undergoing peritoneal dialysis. Ren Replace Ther 9, 18 (2023). https://doi.org/10.1186/s41100-023-00472-5