|Year : 2020 | Volume
| Issue : 1 | Page : 72-77
Continuous ambulatory peritoneal dialysis peritonitis: Microbiology and outcomes
Girisha Pindi, Vijendra Kawle, Rajeshwar Rao Sunkara, Murty Satyanarayana Darbha, Sasikala Garikaparthi
Department of Clinical Microbiology, Osmania General Hospital, Hyderabad, Telangana, India
|Date of Submission||12-Jun-2020|
|Date of Decision||17-Jun-2020|
|Date of Acceptance||26-Jun-2020|
|Date of Web Publication||25-Jul-2020|
Dr. Girisha Pindi
10-3-313/14, P.S. Nagar, Vijay Nagar Colony, Hyderabad - 500 057, Telangana
Source of Support: None, Conflict of Interest: None
Context: Continuous ambulatory peritoneal dialysis (CAPD) is now a preferred mode of the treatment in patients with end-stage renal disease, but peritonitis remains to be a shortcoming of CAPD. High-culture negativity, emerging drug resistance and peritoneal dialysis (PD)-related morbidity and mortality have been a challenge to tackle. Aims: The present study was taken up to compare the the various culture methods and to identify the spectrum of organisms causing CAPD peritonitis and their outcome. Settings and Design: A prospective, observational, cross-sectional study was conducted at a tertiary care teaching hospital in Hyderabad over a period of 1 year. Subjects and Methods: Dialysate fluid from 100 episodes of clinically suspected peritonitis in 75 patients was processed by conventional centrifuging, water lysis, direct inoculation and addition of centrifuged pellet into brain–heart infusion broth and by automated blood culture system. Identification and antibiotic susceptibility of organisms was done, and the outcome of PD-related peritonitis was analysed. Statistical Analysis Used: The categorical data and continuous data were analysed using the Chi-square test and Student's t-test, respectively. P < 0.05 was considered statistically significant. Results: Of the 100 PD fluids, 87 were culture positive. Automated blood culture systems detected 87 episodes, whereas conventional centrifuge method detected only 53 episodes (P = 0.00001). Peritonitis due to Gram-negative organisms (62.3%) was higher than that of Gram-positive peritonitis (31.1%) and fungi (6.4%). Nineteen per cent episodes were constituted by relapse (9), refractory (4), recurrent (4) and repeat (2) peritonitis. Outcomes were analysed as recovery (77%), catheter removal (15%) and death (2.6%). Conclusions: Direct inoculation of peritoneal fluid into automated blood culture bottles increases the positivity rate and also aids in the early detection of CAPD peritonitis, helping reduce morbidity and mortality of PD patients.
Keywords: Automated blood culture, continuous ambulatory peritoneal dialysis, peritoneal dialysis infections, peritoneal dialysis peritonitis outcome, peritoneal dialysis, peritonitis
|How to cite this article:|
Pindi G, Kawle V, Sunkara RR, Darbha MS, Garikaparthi S. Continuous ambulatory peritoneal dialysis peritonitis: Microbiology and outcomes. Indian J Med Microbiol 2020;38:72-7
|How to cite this URL:|
Pindi G, Kawle V, Sunkara RR, Darbha MS, Garikaparthi S. Continuous ambulatory peritoneal dialysis peritonitis: Microbiology and outcomes. Indian J Med Microbiol [serial online] 2020 [cited 2020 Aug 7];38:72-7. Available from: http://www.ijmm.org/text.asp?2020/38/1/72/290690
| ~ Introduction|| |
Chronic kidney disease (CKD) in India has a reported prevalence of 17.4%. Continuous ambulatory peritoneal dialysis (CAPD) has become the popular and preferred mode of treatment of patients with end-stage renal disease (ESRD) with up to 29% of them being on CAPD. However, the greatest limiting factor to the augmentation of CAPD is peritoneal dialysis (PD)-related infections, especially peritonitis, either alone or in conjunction with exit-site and tunnel infections. Peritonitis continues to be the most frequent cause of technique failure and leads to significant morbidity along with a reported mortality of up to 18%.
Peritonitis rates may vary widely between centres, even in the same country or region. Microbiological spectrum of CAPD peritonitis in developing countries such as India may be different from that noted in developed countries, and this may be due to the differences in environmental, social, educational and financial background of the patients on PD.
International Society for PD (ISPD) guidelines state that antibiotic treatment must be adjusted based on the microscopy or culture results after the initial empiric therapy for CAPD peritonitis. Isolation and identification of the causative organism to prevent unnecessary broad-spectrum antibiotic exposure, continues to be a diagnostic challenge with several methods being used to improve the sensitivity of culturing dialysates including automated blood culture, centrifugation, enrichment, large volume culture, filtration and cell lysis. This study was aimed to identify the risk factors, compare the different culture methods for the diagnosis, identify the spectrum of the causative organisms and analyse the outcomes of CAPD peritonitis.
| ~ Subjects and Methods|| |
This prospective, observational cross-sectional study was conducted at a tertiary care teaching hospital in Hyderabad over a period of 1 year, after obtaining the Institutional Ethics Committee approval and patient consent. A total of 100 episodes of clinically suspected peritonitis in 75 patients were analysed. Definitions of peritonitis, repeat, relapse, recurrent and refractory peritonitis were defined according to the ISPD criteria. Peritonitis secondary to non-infective causes were excluded. Detailed history with demographic and clinical characteristics was recorded, including aetiology of ESRD, presence of comorbidities, previous peritonitis episodes and the time taken to the current peritonitis episode.
The patient's exchange bags containing effluent dialysate were delivered to the laboratory within 30 min. All bags were inspected for any obvious leaks. Dialysate fluid was drawn with a sterile needle and syringe under aseptic conditions and processed by automated blood culture method, conventional brain–heart infusion (BHI) broth inoculation, centrifugation, and water lysis, as shown in [Figure 1].
Identification and susceptibility testing was performed using the VITEK 2 compact-automated identification system and interpreted as per the CLSI guidelines. The categorical data were analysed using the Chi-square test and represented as frequency and continuous data analysed using the Student's t-test and represented as mean or median. P < 0.05 was considered statistically significant.
The outcomes were analysed as recovery, catheter loss and death within 4 weeks of peritonitis.
| ~ Results|| |
The study included 100 episodes of clinically suspected peritonitis in 75 patients undergoing CAPD. The mean duration of dialysis in these patients was 27.1 ± 21.8 (ranging 6–92) patient-months. The incidence of peritonitis was most in the age group of 41–50 years (32%), with a mean age being 45 ± 6 years and showed male preponderance (70.6%). [Table 1] shows aetiology of the ESRD. Diabetic nephropathy (41.3%) emerged as the most common cause of ESRD followed by hypertensive nephropathy (32%) and chronic interstitial nephritis (CIN) (14.6%). Ninety-six per cent (72/75) of patients had one or more non-renal comorbidity which included coronary artery disease, cerebrovascular disease, peripheral vascular disease, diabetes mellitus, and hypertension. The majority 51/75 (68%) of the patients had more than two of these comorbidities. [Table 2] shows the clinical findings of peritonitis. Abdominal pain (94%) and cloudy PD bag (94%) were among the most common clinical findings of peritonitis.
Out of a total 100 dialysates, 87 (87%) were culture positive and 13 (13%) were culture negative. The culture positivity derived using different culture methods is shown in [Table 3]. Of 87 culture-positive fluids, 53 showed growth using conventional centrifuge culture, and all these fluids also showed growth when using the remaining four methods. The water lysis method detected 12 more positive cultures. Direct inoculation of 10 ml effluent into BHI broth resulted in culture positivity in 15 additional fluids. Inoculation of the centrifuged pellet into BHI broth increased the positivity by growth in an additional 25 fluids compared with the conventional culture method. Moreover, inoculation of PD effluent into automated blood culture bottles lead to 34 additional positive cultures. Ten additional isolates that were detected by inoculation of the centrifuged pellet into BHI broth were not identified by direct inoculation of CAPD fluid into BHI broth. Water lysis method could identify six isolates (1 Candida glabrata, 4 Staphylococcus aureus and 1 coagulase-negative staphylococci [CONS]) that could not be identified by conventional centrifugation, addition of centrifuged pellet into BHI broth or direct inoculation of fluid into BHI.
A total of 93 organisms were isolated in 87 episodes of peritonitis. Of these 58 isolates were Gram-negative bacilli, 29 isolates were Gram-positive cocci and 6 isolates were fungi [Table 4]. Nearly 6.8% (n = 6/87) of the culture-positive peritonitis episodes were polymicrobial. Three of six fungal episodes were associated with CONS (2 Candida albicans and 1 Aspergillus flavus). The other polymicrobial combination growths were one each of Klebsiella oxytoca + S. aureus, Klebsiella pneumoniae + Mucor, K. pneumoniae + Escherichia coli.
Antibiotic susceptibility testing of Gram-positive organisms showed that 40.7% (11/27) Staphylococcus spp. were methicillin resistant and 44.4% (12/27) showed Macrolide-lincosamide-streptogramin B constitutive/inducible resistance. One of the two Enterococcus spp. showed high-level gentamicin resistance. Hundred percent sensitivity was noted for vancomycin, teicoplanin and linezolid in all Gram-positive cocci. Among the Gram-negative organisms, 58.6% (34/58) isolates were extended-spectrum beta-lactamases (ESBL) producers mainly constituted by K. pneumoniae (13/18) and E. coli (12/16). One each of K. pneumoniae and Acinetobacter baumannii isolates were carbapenem resistant. High sensitivity was noted for imipenem 96.5% (56/58), piperacillin-tazobactam 79.3% (46/58) and gentamicin 74.1% (43/58).
Eighty-one percent were solitary episodes, whereas 19% episodes constituted relapse, refractory, recurrent and repeat peritonitis with majority being relapse (n = 9) [Table 5]. Eleven episodes of peritonitis were associated catheter-related infections [Table 6].
Recovery was noted in 68% patients (n = 51/75) and 77% episodes (n = 77/100). Fifteen patients needed catheter removal which included all fungal and refractory peritonitis. K. pneumoniae peritonitis was noted in 18 episodes of which 12 recovered and 4 required removal of catheter. Nearly 2.6% (n = 2/75) patients had peritonitis associated mortality, and both were polymicrobial on culture (K. pneumoniae + Mucor species-1; K. pneumoniae + E. coli-1). Two patients were taken up for renal transplantation [Table 7].
| ~ Discussion|| |
Peritonitis is the major Achilles heel of CAPD. Many centres have reported peritonitis in CAPD patients with varying rates of culture positivity depending on the centre's PD experience.,,,,,, The nephrology department in our teaching government hospital caters to more than 150 outpatients per day and provides services to patients from all age groups. CAPD was initiated in our centre in 2014.
In our study, the incidence of peritonitis was more in the age group of 41–50 years followed by 31–40 years, with the mean age being 45 ± 6 years similar to a study, which reported the mean age of developing peritonitis to be 42.6 ± 14.9 years. Diabetic nephropathy (41.3%) emerged as the most common cause of ESRD followed by hypertensive nephropathy (32%) and CIN (14.6%). Various studies have shown that diabetes not only emerged as a forerunner in causation of CKD but has been proven to be an independent risk factor for the development of peritonitis., It leads to faster decline of renal function. Altered immunity of peritoneal defences in diabetes is evidenced by the impaired migration of phagocytes into the peritoneum and suppression of phagocytosis by advanced glycation end products. Ninety-six percent (72/75) of patients had one or more non-renal comorbidity. The majority (68%) of the patients had ≥2 comorbidities.Another study also noted that 100% of the patients had one or more non-renal comorbidity and that 62% of the patients had ≥2 comorbidities. Abdominal pain (94%) and cloudy PD bag (94%) were the most common symptoms of peritonitis. Costa et al. also found that cloudy peritoneal effluent (95%) and abdominal pain (93%) were the most common symptoms in their study.
The ISPD guidelines recommend that culture negativity should not be more than 20%. The culture positivity (87%) in our study was as per the recommended range and also similar to that of other studies.,, Prasad et al. reported that their culture negativity reduced from 36.9% in 2003 to 18.2% in 2014 owing to the improvement in microbiological culture technique. The use of automated blood culture systems was statistically proven to be significant over other culture methods (P ≤ 0.00001). ISPD guidelines recommend that the standard method for culture is the use of blood-culture bottles, but a large volume culture could further improve the culture isolation rates. More studies have inferred that the use of the BACTEC bottle method resulted in more positive culture results than did conventional culture (86.8 vs. 57.9% P = 0.003) within lesser time (90 vs. 109 h, P = 0.03)., The enrichment of centrifuged pellet in BHI broth and the release of intracellular organisms using water lysis resulted in more culture yield compared to conventional culture in our study. Iyer et al. also showed that the combination of Tween-80, water lysis and Triton-X treatment resulted in higher culture positivity, attributing it to the release of intracellular organisms present in phagocytes by prior treatment of the specimen with chemical and physical methods.
We reported a higher incidence of Gram-negative peritonitis 62.3% (58/93). Published reports from India showed that Gram-negative pathogens account for 60%–65% of all positive cultures. A study by Gadola et al. found that although 44% of the culture isolates were Gram-positive and only 20% were due to Gram-negative, the adverse outcomes and mortality rate due to Gram-negative peritonitis was significantly higher than that due to Gram-positive organisms (P < 0.05). Improved connection technology eliminating spike systems, programs for tracking peritonitis, Staphylococcus aureus prophylaxis, and the use of the new, more biocompatible dialysis solutions may account for the reduction in Gram-positive peritonitis. The most common Gram-negative isolate was K. pneumoniae followed by E. coli constituting 19.3% and 17.2% of the total isolates and 31.03% and 27.58% of the total Gram-negative isolates, respectively. Lin et al. also reported a very high incidence of K. pneumoniae (16%) in their study, and these patients had a higher incidence of sepsis or bacteraemia and higher mortality rates and underwent PD therapy for a longer period. In our study, S. aureus was the most common Gram-positive isolate followed by CONS and Enterococcus. ISPD guidelines state that CONS is usually associated with touch contamination, Enterococcus of faecal origin, whereas S. aureus is associated with exit site or tunnel infection. Six episodes of peritonitis were associated with the isolation of fungi which was comparable to another study. It poses a significant risk of removing patients from the PD program. ISPD guidelines recommend the administration of anti-fungal prophylaxis when PD patients receive antibiotic courses to prevent fungal peritonitis.
Eighty-one per cent (n = 81/100) of episodes were solitary, whereas 19% (n = 19/100) episodes constituted relapse, refractory, recurrent and repeat peritonitis with majority being relapse (n = 9). Nessim et al. in their study stated that the first peritonitis episode was associated with an increased risk for developing a subsequent episode along with the formation of a biofilm on PD catheter which puts patients at increased risk of subsequent infection due to the difficulty in eradicating organisms. Of 100 PD peritonitis, four episodes were refractory to the treatment in our study. Gram-negative peritonitis were more refractory and three of four episodes were caused by Klebsiella species, all three being ESBL-producing isolates. A study reported refractory peritonitis to be 12.5% episodes of peritonitis and were associated with longer time of treatment and hospital stay and increased peritoneal count at the fifth day. The rates of relapse, recurrence and repeat peritonitis were 9%, 4% and 2%, respectively, in our study, comparable to other studies., Catheter removal was done in relapsing and refractory episodes of peritonitis. It has been shown as an effective measure to prevent the relapse in other studies. Two episodes of repeat peritonitis were seen each caused by E. coli and CONS. Nessim et al. found that the most common infecting organism in repeat peritonitis was CONS, seen in 65.7% of patients and that it was associated with intraluminal introduction of organisms into the peritoneal cavity, suggesting breaks in sterile technique.
Eleven PD-related peritonitis episodes were associated with catheter-related infections in our study. Another study concluded that exit site infection was independently associated with a complicated course of peritonitis and lesser response to antimicrobial therapy, catheter loss and increased morbidity. In the present study, it was seen that Gram-positive cocci constituted a majority of exit site infections with S. aureus and CONS being the most common organisms. P. aeruginosa was the most common organism associated with tunnel infection (66.6%). S. aureus and P. aeruginosa exit site infections are associated with tunnel infections and cause catheter infection-related peritonitis requiring aggressive management.
Failure rate of PD is stated to be higher in patients infected with ESBL-producing organisms. In our study, 58.6% of Gram-negative bacteria were ESBL producers. In different studies from India ESBL rates varied from 35.8% to 67.4%., Nearly 25.8% of Gram-negative isolates were resistant to gentamicin. Aminoglycosides and cephalosporins are frequently used for Gram-negative coverage in PD peritonitis. The evolving resistance may restrict their use in the treatment. The prevalence of methicillin-resistance was 40.7%, as compared with previous reports of 28.6%. It is associated with an increased risk of relapse and with worse outcomes of Staphylococcal infections.
In our study, 6% of the peritonitis episodes were polymicrobial. Barraclough et al. found that polymicrobial episodes constituted 10% of all the peritonitis episodes, whereas two other studies reported a lesser incidence of 2% and 1.6%, respectively., A study from Australia reported that polymicrobial peritonitis lead to the higher rates of hospitalisation, catheter removal, transfer to haemodialysis and death. Evaluation of clinical behaviour of polymicrobial peritonitis in our study showed that three patients were cured, two patients required catheter removal and two patients expired. All these patients needed extended hospitalisation.
Our study showed an overall primary cure rate of 77% (77/100 episodes). Catheter removal was done in 15% (15/100) of which five were episodes of fungal peritonitis, four were refractory to treatment and six patients had relapsing episodes. Two patients expired as a consequence of infection and septicaemia due to peritonitis. Two patients were taken up for renal transplantation.
| ~ Conclusions|| |
In our study, the rate of Gram-negative peritonitis was higher than that of Gram-positive peritonitis. Direct inoculation of peritoneal fluid into automated blood culture bottles yielded higher culture positivity rate followed by enrichment of centrifuged pellet in BHI broth and the procedure of water lysis. Fungal and polymicrobial peritonitis increased the rate of morbidity and mortality. The finding that drug-resistant organisms have caused relapse and refractory peritonitis highlights the need for constant surveillance of causative organisms and emerging drug resistance patterns to develop an antibiotic policy exclusively for PD-related infections based on local susceptibility of the isolated pathogens. However, a larger sample size is required to draw firm conclusions.
We are thankful to Dr Manisha Sahay, Prof. and HOD, Department of Nephrology, Osmania general Hospital, Hyderabad, Telangana and Department of Nephrology for the guidance and support.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]