Relapsing CoNS PeritonitisBY

Dr. Ahmed Moustafa Taha Mohamed

DaVita KSA

Buraydah Center

PD Orientation Program

What is Staphylococci ?

from the Greek: σταφυλή, which means "grape"

κόκκος, which means"granule"

Staphylococcus is a genus of gram positive bacteria. Under the microscope, they appear round (cocci), and form in grape-like clusters.

includes at least 40 species .

Most are harmless and reside normally on the skinand mucous membranes

Coagulase Production

One of the most important phenotypical features used in the classification of staphylococci is their ability to produce coagulase, an enzyme that causes blood clot formation.

Staphyloccocci can be classified according to its ability to produce Coagulase as Coagulase Positive and Coagulase negative .

S.Aureas is coagulase positive species .

S. epidermidis, a coagulase-negative species, is a commensal of the skin, but can

cause severe infections in Immunocompromised patients and those with central venous catheters.

S. saprophyticus, another coagulase-negative species that is part of the normal Vaginal Flora, In recent years, several other Staphylococcus species have been implicated in human infections, notably S. lugdunensis,S. schleiferi, and S. caprae.

Common abbreviations for coagulase-negative staphylococci are CoNS and CNS.

So Why CoNS is Important in PD Care ?

According to Most Studies there is a significant decrease in Peritonitis incidence through the last 30 years .

This usually is attributed to introduction of safer connection methods , and for antibiotic prophylaxis .

But the CoNS induced peritonitis in PD patients did not Improve or decrease .

In many centers, coagulas enegative Staphylococcus (CoNS) species are its most frequent causes of Peritonits.

Clin J Am Soc Nephrol 9: 1074–1081, 2014.

Clin J Am Soc Nephrol 9: 1074–1081, 2014.

Coagulase negative staphylococci

Coagulase-negative staphylococcus peritonitis, including S. epidermidis, is due primarily to touch contamination,is generally a mild form of peritonitis,and responds readily to antibiotic therapy but can sometimes lead to relapsing peritonitis due to biofilm involvement. In such circumstances, catheter replacement is advised (Evidence)

Methicillin resistance in CoNS

Patients with S. Epidermidis peritonitis have mild pain and often can be managed as outpatients. In some programs, and depending on the precise species involved, there is a very high rate of methicillin resistance (>50%); therefore, these programs may wish to use vancomycin as empiric therapy.

Methicillin resistance of staphylococci is defined as the presence of the mecAgene and indicates that the organism is considered resistant to all beta-lactam-related antibiotics, including penicillins, cephalosporins, and carbapenems.

Every effort should be made to avoid inadequate levels that may lead to relapsing peritonitis.

Ideally, repeated cell counts and cultures of the effluent should guide the therapy but 2 weeks of therapy is generally sufficient.

ISPD

Guidelines

Algorithm

Relapsing peritonitis

Relapsing S. epidermidis peritonitis suggests colonization

of the intra-abdominal portion of the catheter

with biofilm and is best treated by replacing the catheter.

This can be done under antibiotic coverage

as a single procedure once the effluent clears with antibiotic

therapy. Often, hemodialysis can be avoided by

using either supine PD or low volumes for a short period

of time.

ISPD Guidelines

INTRAPERITONEAL UROKINASE AND ORAL RIFAMPICIN FOR PERSISTING ASYMPTOMATIC DIALYSATE INFECTION FOLLOWING ACUTE COAGULASE-NEGATIVE STAPHYLOCOCCUS PERITONITIS

Coagulase-negative staphylococcus (CoNS) is responsible for cases of refractory and relapsing peritonitis in peritoneal dialysis (PD) patients, probably by biofilm formation on the catheter. The ISPD recommends

catheter removal in such cases. Urokinase has been used to dissolve the biofilm lining the PD catheter, thus favoring antibiotic efficacy. Rifampicin has shown its efficacy in penetrating CoNS biofilm.

Peritoneal Dialysis International, Vol. 29, pp. 548–553

Continued

Persisting asymptomatic CoNS dialysate infection defined as a peritonitis episode with clinical improvement within 48 hours and dialysate clearing, but with persisting positive dialysate cultures.

intraperitoneal (IP) urokinase (100000 units) and oral rifampicin (600 mg every day for 3 weeks) were added to intravenous vancomycin.

IP urokinase instillation was performed an average of 19 days (range 11 –30) days after peritonitis onset. Treatment success, defined by peritonitis resolution with sterilization of the dialysate.

Conclusion: IP urokinase and oral rifampicin in addition to conventional antibiotics resulted in a catheter salvage rate of 64% in persisting asymptomatic dialysate infection

Peritoneal Dialysis International, Vol. 29, pp. 548–553

USE Of Alteplase tPA in CoNS relapsing peritonitis

tPA was also administered to 5 patients with relapsing peritonitis; 3 patients, all with Staphylococcus epidermidis, recovered and did not experience further recurrence.

8 mgs in 10 ml (up to 10 mg/10 ml may be used) of sterile water injected into the catheter and allowed to dwell for 1 hour)

Nephrol Nurs J. 2004 Sep-Oct;31(5):534-7.

A High Serum Vancomycin Level Is Associated with Lower Relapse Rates in Coagulase-Negative Staphylococcal Peritonitis

The standard protocol for empiric treatment of peritonitis in our unit is cefazolin (1.5 – 2 g) and ceftazidime (1.5 – 2 g), with adjustment of antibiotic dosing based on culture and sensitivity results. For patients with methicillin-resistant CNS (or a history of penicillin allergy), vancomycin is given intraperitoneally at an initial dose of 15 – 20 mg/kg every 3 – 4 days, with the subsequent dose and frequency being adjusted to maintain a target serum level of 15 – 20 mg/L. Trough serum vancomycin is checked once weekly during therapy. Incident CNS peritonitis is treated for 2 weeks per the ISPD recommendations. Relapsed and early repeat CNS peritonitis are variably treated with catheter removal or a second course of antibiotics, often accompanied by either or both of rifampin and a single instillation of tissue plasminogen activator (tPA) into the catheter.

Dahlan R et al ..Perit Dial Int. 2014 Mar-Apr;34(2):232-5.

Recommendation :

that serum trough levels be

maintained above 15 mg/L,

with repeat dosing when

the trough level falls below

20 mg/L for patients with

an incident CNS peritonitis.

What is Happening WORLD WIDE with CoNS in PD

HONG KONG

Coagulase Negative Staphylococcal Peritonitis in Peritoneal Dialysis Patients: Review of 232 Consecutive Cases

All of the coagulase-negative Staphylococcus species peritonitis in a dialysis unit from 1995 to 2006 were reviewed. During this period, there were 2037 episodes of peritonitis

recorded; 232 episodes(11.4%) in 155 patients were caused by coagulase-negative Staphylococcus species.

Results: The overall primary response rate was 95.3%; the complete cure rate was 71.1%. Patients with a history of recent hospitalization or recent antibiotic therapy had a higher risk for developing methicillin-resistant strains. Episodes that were treated initially with cefazolin or vancomycin had similar primary response rate and complete cure rate. There were 33 (14.2%) episodes of relapse and 29 (12.5%) episodes of repeat peritonitis; 12 (60.6%) of the repeat episodes developed within 3 mo after completion of antibiotics. Relapse or repeat episodes had a significantly lower complete cure rate than the other episodes. For relapse or repeat episodes, treatment with effective antibiotics for 3 wkwas associated with a significantly higher complete cure rate than the conventional 2-wk treatment.

Szeto et al.Clin J Am Soc Nephrol 3: 91–97, 2008.

Conclusions

Coagulase-negative Staphylococcus species peritonitis remains a common complication of peritoneal dialysis.

Methicillin resistance is common, but the treatment outcome remains favorable when cefazolin is used as the first-line

antibiotic.

A 3-wk course of antibiotic can probably achieve a higher cure rate in relapse or repeat episodes.

Szeto et al.Clin J Am Soc Nephrol 3: 91–97, 2008.

What is Happening WORLD WIDE with CoNS in PD

Australia

Coagulase-negative staphylococcal peritonitis in Australian peritoneal dialysis patients: predictors, treatment and outcomes in 936 casesA total of 936 episodes of CNS peritonitis (constituting 26% of all peritonitis episodes) occurred in 620 individuals. The observed rate of CNS peritonitis was 0.16 episodes per patient-year. Lower rates of CNS peritonitis were independently predicted by Asian racial origin, renovascular nephrosclerosis, early referral to a renal unit prior to dialysis commencement and treatment with automated PD at any time during the PD career. The majority of CNS peritonitis episodes were initially treated with intraperitoneal vancomycin or cephazolin in combination with gentamicin. This regimen was changed in 533 (57%) individuals after a median period of 3 days, most commonly to vancomycin monotherapy. The median total antibiotic course duration was 14 days. Compared with other forms of peritonitis, CNS episodes were significantly more likely to be cured by antibiotics alone (76 vs 64%, P < 0.001) and less likely to be complicated by hospitalization (61 vs 73%, P < 0.001), catheter removal (10 vs 26%, P < 0.001), temporary haemodialysis (2 vs 5%, P < 0.001), permanent haemodialysis transfer (9 vs 21%, P < 0.001) and death (1.0 vs 2.7%, P = 0.002). CNS peritonitis was also associated with a shorter duration of hospitalization, a longer time to catheter removal and a shorter duration of temporary haemodialysis. Catheter removal and permanent haemodialysis transfer were independently predicted by polymicrobial peritonitis and initial empiric administration of vancomycin (compared with cephalosporins). CNS peritonitis was associated with a higher relapse rate (17 vs 13%, P = 0.003) and relapsed CNS peritonitis was associated with a higher catheter removal rate (22 vs 7%, P < 0.001). Repeat peritonitis occurred in 194 (31%) individuals and the highest risk was in the second month after completion of antibiotic treatment for CNS peritonitis compared with >2 months).

Fahim et al .Nephrol Dial Transplant (2010) 25: 3386–3392

CONCLUSIONS

CNS peritonitis is a common complication with a relatively benign outcome compared with other forms of PD-associated peritonitis. Relapsed and repeat peritonitis are relatively common and are associated with worse outcomes.

Fahim et al .Nephrol Dial Transplant (2010) 25: 3386–3392

What is Happening WORLD WIDE with CoNS in PD

Brazil

Peritoneal Dialysis–Related Peritonitis due toCoagulase-Negative Staphylococcus: A Reviewof 115 Cases in a Brazilian Center

This study reviewed the records of 115 CNS peritonitis episodes that occurred in 74 patients between 1994 and 2011 at a single university center. Peritonitis incidences were calculated for three consecutive 6-year periods (P1, 1994-1999; P2, 2000-2005; P3, 2006-2011) and annually. The production of biofilms, enzymes, and toxins was evaluated. Oxacillin resistance was evaluated based on its minimum inhibitory concentration and the presence of the mecAgene.

RESULTS

The overall incidence of CNS peritonitis was 0.15 episodes per patient per year and did not vary over time (0.12, 0.14, and 0.16 for P1, P2, and P3, respectively; P=0.21). The oxacillin resistance rate was 69.6%. Toxin and enzyme production was infrequent and 36.5% of CNS strains presented the gene encoding biofilm production. The presence of icaAD genes associated with biofilm production was predictive of relapses or repeat episodes (odds ratio [OR], 2.82; 95% confidence interval [95% CI], 1.11 to 7.19; P=0.03). Overall, 70 episodes (60.9%) resolved; oxacillin susceptibility (OR, 4.41; 95% CI, 1.48 to 13.17; P=0.01) and vancomycin use as the first treatment (OR, 22.27; 95% CI, 6.16 to 80.53; P<0.001) were the only independent predictors of resolution.

Conclusions

Oxacillin resistance and vancomycin use as the first treatment strongly influence the resolution rate in CNSperitonitis, which reinforces the validity of the International Society for Peritoneal Dialysis guidelines on monitoring bacterial resistance to define protocols for initial treatment. These results also suggest that the presence of biofilm is a potential cause of repeat peritonitis episodes.

Clin J Am Soc Nephrol 9: 1074–1081, 2014.