Management of Coagulase Negative Staphylococcus , Relapsing , Evidence Based , Most Famous respectful Studies in this Topic , CNS , CONS

1. Relapsing CoNS Peritonitis
BY
Dr. Ahmed Moustafa Taha Mohamed
DaVita KSA
Buraydah Center
PD Orientation Program

2. 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 skin
and mucous membranes

3. 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.

4. 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.

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

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

8. 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)

9. 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 mecA
gene 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.

10. ISPD
Guidelines
Algorithm

11. 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

12. 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

13. 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

14. 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.

15. 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.

16. 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.

17. What is Happening WORLD WIDE with CoNS in PD
HONG KONG

18. 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 wk
was 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.

19. 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.

20. What is Happening WORLD WIDE with CoNS in PD
Australia

21. Coagulase-negative staphylococcal peritonitis in
Australian peritoneal dialysis patients: predictors,
treatment and outcomes in 936 cases
A 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

22. 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

23. What is Happening WORLD WIDE with CoNS in PD
Brazil

24. Peritoneal Dialysis–Related Peritonitis due to
Coagulase-Negative Staphylococcus: A Review
of 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 mecA
gene.

25. 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.

26. 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.