ΕΙΔΙΚΗ ΑΝΤΙΜΕΤΩΠΙΣΗ ΠΕΡΙΤΟΝΙΤΙΔΑΣ ΚΛΙΝΙΚΕΣ ΟΔΗΓΙΕΣ...

ΕΙΔΙΚΗ ΑΝΤΙΜΕΤΩΠΙΣΗ ΠΕΡΙΤΟΝΙΤΙΔΑΣ

ΚΛΙΝΙΚΕΣ ΟΔΗΓΙΕΣ ISPD

ΠΗΝΕΛΟΠΗ ΧΡ. ΚΟΥΚΗ

«ΙΠΠΟΚΡΑΤΕΙΟ» Γ.Ν.Α

REFRACTORY(ANΘΕΚΤΙΚΗ) PERITONITIS

Failure of the effluent to clear after 5 days of appropriate antibiotics

RECURRENT (YΠΟΣΤΡΟΦΟΣ) PERITONITIS

Αn episode that occurs within 4 weeks of completion of therapy of a prior episode but with a different organism

RELAPSING (ΥΠΟΤΡΟΠΙΑΖΟΥΣΑ) PERITONITIS

An episode that occurs within 4 weeks of completion of therapy of a prior episode

with the same organism or 1 sterile episode

REPEATED (ΕΠΑΝΑΛΑΜΒΑΝΟΜΕΝΗ) PERITONITIS

An episode that occurs more than 4 weeks aftercompletion of therapy of a prior episode with the same organism

Relapsed Recurrent Non-rec, rel

Outcome N= 356 epis N=165 epis N=2021 epis

Hospitalization

No (%) 248 (70) 115 (70) 1473 (73)

Duration (d)

Catheter removal

No (%) 108 (30) 61 (37) 54 (22)

Relapsing and Recurrent Peritoneal Dialysis –Associated Peritonitis : A Multicenter Registry Study. Burke M et al. Am J Kidney Dis. 2011;58(3): 429-436

Relapsed Recurrent

Non-rec, rel

Outcome N= 356 epis N=165 epis N=2021 epis

Temporary hemodialysis

No (%) 21 (6) 11 (7) 80 (4)

Duration (d) 78 99 66.5

Permanent hemodialysis

No (%) 88 (25) 52 (32) 379 (20)

Death (Death of a patient with active peritonitis , or admitted with peritonitis , or within 2 weeks of a peritonitis episode)

No (%) 7 (2.0) 2 (1.2) 7 (2.8)

Freq

uenc

yRepeat

Non-Repeat

120-

100-

80-

60-

40-

20-

0-

Time since previous peritonitis episode (months)

120-

100-

80-

60-

40-

20-

0- 0 6 12 18 24 30 36 42 48

Histogram shows timing of occurrenceof repeated versus non repeated

peritonitis after a prior episode of peritonitis

in Australian peritoneal dialysis patients in2003-2007.

Repeated peritonitis Non-repeated peritonitis

Outcome N = 245 episodes N = 824 episodes

Relapse 83 (34) 77 (9)

Hospitalization

Events (%) 149 (61) 585 (71)

Catheter removal

Events (%) 48 (20) 166 (20)


Events (%) 38 (16) 143 (17)

Death

Events (%) 3 (1.2) 23 (2.8)

Repeated peritoneal dalysis associated peritonitis A multicenter registry study. Thirugnanasambathan T et al.Am J Kidkey Dis xx(x)xxx

ROC curve of dialysate white counts

False-positive proportion (1-Specificity)

Tru

e-p

osi

tive

p

rop

ort

ion

(S

ensi

tivi

ty)

1.00-

.75-

.50-

.25-

0.00-

• White count on day 5



0.00 . 25 .50 .75 1.00

Sensitivity and specificity of dialysate white cellcounts at various time points of the peritonitis to predict treatmentfailure, assessed by receiver-operating characteristic(ROC) curve analysis.

Predictive value of dialysate cell counts in peritonitis complicating peritoneal dialysis. Kai Ming Chow..Clin J Am Soc Nephrol2006;1:768-773

> 1090/mm3

Gram- Positive Organisms, Including Coagulase-Negative Staphylococcus, on CultureDue primarily to touch contaminationLeads sometimes to relapsing peritonitis due to biofilm involve –replacing the catheter under antibiotic coverage as a single procedure once the effluent clears

Continue gram-positive coverage based on sensitivities Stop gram-negative coverage If Methicillin resistance : Definition based on MIC levels and the presence of mec A geneDefined 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.

Assess clinical improvement, repeat dialysis effluent cellcount and culture at days 3-5

Clinical improvement(symptoms resolve; bags clear):

-Continue antibiotics;-Reevaluate for exit-site or

occult tunnel infection, intra –abdominal abscess, catheter

colonization

Duration of therapy : 14 days Peritonitis with exit-site or tunnel infection: Consider catheter removal. Duration of therapy :14-21 days

No clinical improvement(symptoms persist; effluent remains cloudy):

-Reculture and evaluate

No clinical improvement by 5 days on appropriateantibiotics: Remove catheter

Enterococcus/ Streptococcus on Culture-Touch contamination-Intra abdominal pathology- Exit site and tunnel infection- Dental hygiene

Discontinue starting antibioticsStart continuous ampicillin 125mg/L each bag;consider adding aminoglycoside once daily IP as 20mg/L for EnterococcusThe manifacturer’s precaution label states that these antibiotics should not be mixed together in the same solution container

If ampicillin resistant, start vancomycin;If vancomycin – resistant enterococcus, consider quinupristin/dalfopristin, daptomycin or linezolid ( Bone marrow suppresion after 10-14 days)





colonization

Duration of therapy : 14 days (Streptococcus)21 days (Enterococcus)

Peritonitis with exit-site or tunnel infection: Consider catheter removal. Duration of therapy :21 days

Outcome Streptococcal peritonitis

Non-Streptococcal peritonitis

N=287 episodes N=3307 episodes

Hospitalization

Number (%) 212 (74) 2292(69)

Catheter removal

Number (%) 29(10) 746(23)


Number (%) 25(9) 610(18)

Death

Number (%) 4(1) 78(2)

Treatment characteristics and clinical outcomes of PDassociated peritonitis due to streptococci or other organisms in Australia 2003-2006

Streptococcal peritonitis in Australian peritoneal dialysis patients: predictors, treatment and outcomes in 287 cases. Stace O’Shea et al. BMJ Nephrology 2009, 10;19

Outcome Pure enterococcal peritonitis

Polymicrobial enterococcal peritonitis

Non-enterococcal peritonitis

N=64episodes N=52episodes N=3478episodes

Hospitalization

Number(%) 48(75) 43(83) 2413(69)

Catheter removal

Number(%) 16(25) 27(52) 732(21)


Number(%) 11(17) 26(50) 598(17)

Death

Number(%) 1(1.6) 3(5.8) 78(2.2)

Treatment characteristics and clinical outcomes of PDassociated peritonitis due to pure enterococcal, polymicrobial entedrococcal and non-enterococcal in Australia 2003-2006

Enterococcal peritonitis in Australian peritoneal dialysis patients: predictors, treatment and outcomes in 116 cases. Edey M et al. NDT 2010 25:1272-1278

Staphylococcus aureus on CultureTouch contamination-Exit-site or tunnel infection

Continue gram-positive based on sensitivitiesStop gram-negative coverage, assess exit site again

If methicillin resistant, adjust coverage to vancomycin (1gr IP every 5 days) or teicoplaninIf vancomycin – resistant S aureus, consider quinupristin/dalfopristin, daptomycin or linezolid ( Bone marrow suppresion after 10-14 days)

Teicoplanin can be used in a dose of 15mg/kg once dailyAdd Rifampin 600mg/day orally for 5-7 days( 450 mg/day if BW < 50kg)





colonization

Duration of therapy : At least 21 days

Peritonitis with exit-site or tunnel infection may prove to be refractory and catheter removal should be consideredAllow a minimum rest period of 3 weeks before reinitiating PD

Outcome S aureus peritonitis Non S aureus peritonitis

N=503 episodes N=3091episodes

Relapse

Number(%) 100(20) 402(13)

Hospitalization

Number(%) 338(67) 2166(70)

Catheter removal

Number(%) 116(23) 659(21)


Number(%) 93(18) 542(18)

Death

Number(%) 11(2.2) 71(3.3)

Treatment characteristics and clinical outcomes of PDassociated peritonitis due to to Staphylococcus aureus or other organisms in Austalia 2003-2006

Staphylococcus aureus peritonitis in Australian peritoneal dialysis patients: predictors, treatment and outcomes in 503 cases. Govindarajulu S et al.Per Dial Inter. 30;313-319

Treatment characteristics and clinical outcomes of PDassociated peritonitis due to to MSSA and MRSA in Australia 2003-2006

Outcome MSSA peritonitis MRSA peritonitis


Relapse

Number(%) 79(20) 21(19)

Repeat

Number(%0 122(31) 26(24)

Hospitalization

Number(%) 256(65) 82(75)

Catheter removal

Number(%) 82(21) 34(31)


Number(%) 66(17) 27(25)

Death

Number(%) 6(2) 5(5)

Culture negative on Days I and 2Clinical features of peritonitis (abdominal pain or cloudy dialysate), dialysate leukocytosis ( white blood cell count>100/μL with >50% neutrophils) and negative dialysate culture result for any organism ( including fungi and mycobacteria)( Program with >20% culture negative peritonitis- reviewed and improved)

Continue initial therapy

Day 3 : culture still negativeClinical assessment

Repeat PD fluid white cell count and differential

Infection resolvingPatient improvement clinically

Continue initial therapy for 14 days

Infection not resolvingSpecial culture technique for unusual causes

( e.g viral, mycoplasma, mycobacteria, legionella, fungi)

Now culture positiveStill culture negative

Adjust therapy according to

sensitivity patterns.Duration of therapy based on organism

identified

Clinical improvement:

Continue antibiotic therapy

Duration of therapy:14 days

No clinical improvement after 5

days:Remove catheter

Continue antibiotics for at least 14 days after catheter removal

Treatment characteristics and clinical outcomes of culture-negative and culture positive PD associated peritonitis in Australia 2003-2006

Outcome Culture-negative peritonitis

Culture-positive peritonitis


Relapse

Number(%) 62(14) 440(14)

Hospitalization

Number(%) 262(60) 2242(71)

Catheter removal

Number(%) 54(12) 721(23)


Number(%) 43(12) 592(19)

Death

Number(%) 4(1.0) 78(2.5)

Culture negative peritonitis in peritoneal dialysis patients in Australia; predictors, treatment and outcomes in 425 cases. Gahim M et al. Am J Kidney Dis 2010:690-697

Pseudomonas Species on Culture

Without catheter infection (exit-site/tunnel)

Give 2 different antibiotics acting in different ways that organism is sensitive to e.g oral quinolone, ceftazidime.

cefepime, tobramycin, piperacillin



-Continue antibiotics;

Duration of therapy : At least 21 days




Continue oral and/or systemic antibiotics for at least 14 days

Pseudomonas Species on Culture

With catheter infection (exit-site/tunnel)current or prior to peritonitis

Remove catheter

Continue oral and/or systemic antibiotics for at least 14 days

Outcome Pseudomonas peritonitis

Non-Pseudomonas peritonitis

N=191episodes N=3403episodes

Relapse

Number(%) 17(9) 485(14)

Hospitalization

Number(%) 150(79) 2354(69)

Catheter removal

Number(%) 84(44) 691(20)


Number(%) 66(35) 569(17)

Death

Number(%) 6(3) 76(2)

Pseudomonas Peritonitis is Australia: predictors, treatment and outcomes in 191 cases.Siva B et al. Clin J Am Soc Nephrol 2009;4:957-964

Prompt catheter removal and use of two anti-pseudomonal antibiotics are associated with better outcomes

Single Gram-Negative Organism on CultureTouch contamination-Exit site infection-Transmural migration from constipation, diverticulitis or colitis

Other –E.coli, Proteus, Klebsiella etc

Stenotrophomonas(Prior therapy with carbapenemes,

fluoroquinolones, and 3 and 4 generation cephalosporins)

Adjust antibiotics to sensitivity pattern.

Cefalosporin ( ceftazidime or

cefepime) may be indicated-

Fluoroquinolone

Treat with 2 drugs with differing mechanisms

based on sensitivity pattern ( oral trimethoprim/ sulfamethoxazol is

preferred)(IP ticarcillin/clavulanate, per os minocycline)


Other –E.coli, Proteus, Klebsiella etc

Stenotrophomonas

Clinical improvement(symptoms resolve;

bags clear):-Continue antibiotics;-Duration of therapy:

14-21 days

Clinical improvement(symptoms resolve;

bags clear):-Continue antibiotics;-Duration of therapy:

21-28 days

No clinical improvement by 5 days on appropriate antibiotics

(symptoms persist; effluent remains cloudy) : Remove catheter

Fungal peritonitis

Immediately after fungi are identified by microscopy or culture :Remove

catheterStrongly suspected after recent

antibiotic treatment for bacterial peritonitis

• Amphotericin B and flucytosine

Intraperitoneal use of amphotericin causes chemical peritonitisTrough serum flucytosine concentrations < 100μg/mL to avoid bone marrow toxicity

• Fluconazole• Voriconazole ( 200mg IV twice daily for

5 weeks after catheter removal)

• Posaconazole ( 400mg twice daily for

six months) • Caspofungin Used successfully as monotherpy or in combination with amphotericin B

Outcome Fungal peritonitis Non-fungal peritonitis


Hospitalization

Number(%) 159(98) 2345(68)

Catheter removal

Number(%) 142(88) 633(18)


Number(%) 120(74) 515(15)

Death

Number(%) 14(9) 68(2)

Predictors and outcomes of fungal peritonitis in peritoneal dialysis patients. Miles R et al. Kidney Int 2009 76:622-628

The risks of repeat fungal peritonitis and death were lowest with catheter removal combined with antifungal therapy when compared to either intervention alone

Treatment characteristics and clinical outcomes of PD-associated peritonitis due to fungi or other organism in Australia 2003-2006

Effect of timing of catheter removal on subsequent clinical outcomes in 142 patients with fungal peritonitis requiring catheter removal

Characteristic ≤ 5days > 5days



Number(%) 67(86) 53(83)

Death

Number(%) 6(8) 4(6)

Indications for Catheter Removal for Peritoneal Dialysis-Related Infections

• Refractory peritonitis ( Simultaneous catheter removal not possible)

• Relapsing peritonitis ( Catheter removal as a single procedurecan be done if the effluent can first be cleared. The procedure should be done under antibiotic coverage)

• Refractory exit-site and tunnel infection (Timely replacement of the catheter can prevent peritonitis –Permitting simultaneousreplacement)

• Fungal peritonitis ( Simultaneous catheter removal not possible2-3 weeks or later)

• Catheter removal may also be considered for• Repeat peritonitis• Mycobacterial peritonitis• Multiple enteric organisms

ISPD Definitions of Recurrent, Relapsing and Repeated Peritonitis

Time elapsed since completing antibiotics for prior peritonitis episode

SameOrganism

DifferentOrganism

≤ 4w Relapse Recurrence

> 4w Repeated Non-Repeated

Antibiotics Duration of Therapy

Peritonitis with CI -CR

Catheter removal

Gram (+) organisms Continue gram-positive coverage based on sensitivities

14 days 14-21 days

Steptococccus-Enterococccus

AmpicillinAminoglycoside-Enteroc.

If ampicillin resistant enterococcus, start vancomycin;

If vancomycin – resistant enterococcus, consider quinupristin/dalfopristin,

daptomycin or linezolid

14 days (Streptoc)21 days

(Enteroc)

21 days

Staphylococcus aureus Continue gram-positive based on sensitivities

If methicillin resistant, adjust coverage to vancomycin (1gr IP every 5 days) or

teicoplaninAdd Rifampin

21 days Peritonitis with exit-site or tunnel infection may prove to be refractory

and catheter removal should be considered

Allow a minimum rest period of 3 weeks before reinitiating PD

Pseudomonas species Give 2 different antibiotics acting in different ways that organism is sensitive

to e.g oral quinolone, ceftazidime. cefepime, tobramycin, piperacillin

No catheter infection 21 days

With catheter infection (exit-site/tunnel)

current or prior to peritonitisRemove catheter

14 days

E.coli, Proteus, Klebsiella Cefalosporin ( ceftazidime or cefipime) may be indicated-Fluoroquinolone

14-21 days

Stenotrophomonas Treat with 2 drugs with differing mechanisms based on sensitivity pattern

( oral trimethoprim/ sulfamethoxazol is preferred

21-28 days

Fungal Amphotericin B and flucytosineFluconazoleVoriconazoleCaspofungin

Immediately after fungi are identified by microscopy or culture :Remove catheter

Relapsing and Recurrent Peritoneal Dialysis –Associated Peritonitis : A Multicenter Registry Study. Burke M et al. Am J Kidney Dis. 2011;58(3): 429-436

Repeated peritoneal dialysis associated peritonitis A multicenter registry study. Thirugnanasambathan T et al.Am J Kidkey Dis xx(x)xxx

Streptococcal peritonitis in Australian peritoneal dialysis patients: predictors, treatment and outcomes in 287 cases. Stace O’Shea et al. BMJ Nephrology 2009, 10;19

Enterococcal peritonitis in Australian peritoneal dialysis patients: predictors, treatment and outcomes in 116 cases. Edey M et al. NDT 2010 25:1272-1278

Staphylococcus aureus peritonitis in Australian peritoneal dialysis patients: predictors, treatment and outcomes in 503 cases. Govindarajulu S et al. Per Dial Inter. 30;313-319

Culture negative peritonitis in peritoneal dialysis patients in Australia; predictors, treatment and outcomes in 425 cases. Gahim M et al. Am J Kidney Dis 2010:690-697

Pseudomonas Peritonitis is Australia: predictors, treatment and outcomes in 191 cases. Siva B et al. Clin J Am Sox Nephrol 2009;4:957-964

Predictors and outcomes of fungal peritonitis in peritoneal dialysis patients. Miles R et al. Kidney Int 2009 76:622-628

Predictive value of dialysate cell counts in peritonitis complicating peritoneal dialysis. Kai Ming Chow Clin J Am Soc Nephrol 20061:768-773

ΕΙΔΙΚΗ ΑΝΤΙΜΕΤΩΠΙΣΗ ΠΕΡΙΤΟΝΙΤΙΔΑΣ ΚΛΙΝΙΚΕΣ ΟΔΗΓΙΕΣ...

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