Peritoneal Dialysis-Related Infections

32 Peritoneal Dialysis-Related Infections Cheuk-Chun Szeto, MD, FRCP, and Philip Kam-Tao Li, MD, FRCP, FACP OUTLINE Peritoneal Dialysis-Related Peritonitis, 509 Pathogenesis, 509 Host Defense Mechanisms of the Peritoneal Cavity, 510 Presentation, 511 Diagnosis, 511 Treatment of Peritonitis, 511

Mycobacterial Peritonitis , 515 Complications of Peritoneal Dialysis Peritonitis, 515 Catheter-Related Infections, 516 Definitions, 516 Risk Factors, 516 Treatment, 516 Prevention, 517

Peritoneal dialysis (PD)-related infection is a broad term that encompasses PD-related peritonitis and catheter-related infections (CRIs), and the latter is used as a collective term to describe exit-site infection (ESI) and tunnel infection. PD-related infections are important complications of PD and could lead to serious consequences, including catheter loss,1,2 transfer to hemodialysis, hospitalization, and death.3,4 Peritonitis is the leading cause of technique failure in PD patients.5,6 Although the mortality of a peritonitis episode is <5%, peritonitis is the major contributing cause of death in >15% of PD patients.7,8 Every PD unit should monitor, at least on a yearly basis, the incidence of peritonitis and CRIs.9,10 The latest guideline published by the International Society for Peritoneal Dialysis (ISPD) suggests that rates of peritonitis and CRIs should be reported as the number of episodes per patient-year9,10 rather than as number of patient-month per episode, which was commonly used in the past. There is a substantial variation in the peritonitis rate reported by different countries or even different centers within the same country.11-13 However, the overall peritonitis rate should be no more than 0.5 episodes per year at risk.9

that are commonly grown from specimens in contaminationrelated peritonitis are coagulase-negative staphylococcal species (CNSS) and diphtheroids (Corynebacterium species).15-17 Nasal carriers of Staphylococcis aureus often have the same bacteria on their hands and at the exit sites, which can lead to peritonitis through either touch contamination or CRI. Organisms found in the oral cavity, such as Streptococcus species, may cause peritonitis by droplet spread or transient bacteremia (e.g., after a dental procedure). Approximately 15% to 20% of peritonitis episodes, especially those due to S. aureus or Pseudomonas aeruginosa, are caused by catheter infection.1,18 ESIs can spread to involve the catheter tunnel and then the peritoneum.18,19 Such infections often are refractory or relapsing.20 A warm and humid climate may favor the accumulation of sweat and dirt around the catheter exit site, and therefore the growth and colonization of bacteria, resulting in a seasonal variation in the incidence of PD-related peritonitis that peaks in the months that are hot and humid.21,22 Many bacteria can form biofilm on the walls of catheters. Bacteria within the slime layer of biofilm are protected from host defense and antibiotics.23 Refractory or relapsing peritonitis episodes often are caused by the release of planktonic bacteria from the biofilm.20,24,25 However, biofilm also can be found in asymptomatic PD patients without peritonitis.26 Gram-negative bacteria that cause PD-related peritonitis are generally considered to originate from the bowel.17 Most of these cases are presumably caused by the transmural movement of bacteria rather than perforation. This phenomenon is similar to the scenario of spontaneous bacterial peritonitis in patients with liver cirrhosis.27,28 Uremia per se is associated with impaired intestinal barrier function to macromolecules, bacterial fragments,29,30 and possibly bacteria.31 Constipation,32 diarrhea,33,34 and

PERITONEAL DIALYSIS-RELATED PERITONITIS Pathogenesis PD-related peritonitis could be caused by touch contamination, catheter-related problems, bowel pathology, gynecological disease, or systemic bacteremia. The common microbiological causes of PD-related peritonitis are summarized in Table 32.1. Despite the advances in PD system connectology, touch contamination at the time of the PD exchange remains a common cause of peritonitis.1,14 Organisms

509

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TABLE 32.1  Microbiological Causes of

Peritonitis

Bacteria, % Gram-positive organisms Gram-negative organisms Polymicrobial Mycobacterium species, % Fungus, % Culture negative, %

80 40 30 10 1 2.5 15

diverticular disease may further increase the risk for such happening. Gastric acid inhibitors have been reported to be associated with gram-negative peritonitis.35 Surgical diseases of intraabdominal organs also may result in enteric peritonitis.36,37 Traditionally, polymicrobial peritonitis is believed to be caused by the perforation of internal viscera, and surgical exploration often is recommended.38,39 Recent reports show that many patients with PD-related polymicrobial peritonitis do not have overt surgical pathology in the abdomen and response to antibiotic therapy alone often is satisfactory.40,41 Peritonitis may follow colonoscopy with polypectomy,37 hysteroscopy,42 endoscopy with sclerotherapy,43 and dental procedures.44 Peritonitis after dental procedures is most likely related to transient bacteremia. Vaginal leak of dialysate,45 the use of intrauterine devices,46 and endometrial biopsy47 are other recognized contributing factors of PD-related peritonitis. Because of the risk for peritonitis related to such procedures, antibiotic prophylaxis administered before any such procedure is necessary. Antibiotic prophylaxis should be given before colonoscopy and invasive gynecological procedures.9 

Host Defense Mechanisms of the Peritoneal Cavity

Uremia per se causes a wide range of defects in the immunological defense against infection, which is beyond the scope of this chapter. Both humoral and cellular factors participate in the local peritoneal defense processes against peritonitis.48 Under physiological circumstances, bacteria entering the peritoneal cavity are digested by resident peritoneal macrophages and neutrophils. Individual variation in the phagocyte function may partly account for interindividual variation in the risk for peritonitis.49

Humoral Immunity The concentrations of immunoglobulin G (IgG) and complement in normal peritoneal fluid are similar to serum. In PD effluent, however, these values are reduced by 100- to 1000fold,50,51 even after several hours of dwell time. This dilutional effect severely compromises the humoral immunity within the peritoneal cavity. An inverse relationship between the frequency of PD-related peritonitis and peritoneal opsonic activity or IgG concentration has been reported.52 For mechanisms that are not entirely clear, the opsonic activity of spent dialysate against gram-negative bacteria is

substantially lower than that against gram-positive bacteria.52 This may partly account for the greater clinical severity of gram-negative peritonitis. In addition to complement, fibronectin has opsonic activity against gram-positive organisms.53 Low fibronectin concentrations in spent dialysate is a risk factor of PD-related peritonitis.50 

Cellular Immunity The leukocyte count in PD effluent is 100- to 1000-fold less than in normal peritoneal fluid.54 Macrophage is the predominant cell type in noninfected spent dialysate; lymphocyte percentages vary between 2% and 84%, and polymorphonuclear leukocytes (PMNs) are usually 5% to 10%.55 However, baseline peritoneal leukocyte count is not associated with the risk for PD peritonitis.55 When there is peritonitis, neutrophils and macrophages quickly migrate from the systemic circulation and interstitial matrix into the peritoneal cavity. Lymphocytes and cell-mediated cytotoxicity do not play a significant role in the defense against bacterial peritonitis. On the other hand, resident peritoneal macrophages constitute the first line of defense against bacterial invasion. Peritoneal macrophages probably originate from blood monocytes, and their phagocytic and bacteria-killing capacity from PD patients is normal when incubated in culture media.48 However, the oxidative metabolism of macrophages is reduced in dialysis solution54 or after repeated peritonitis episodes.51 PMN from PD patients exhibit decreased binding of C5a, decreased chemotaxis, and impaired opsonic activity.54 Mesothelial cells along the peritoneal membrane also play important roles in the local defense against peritonitis.56 The interaction between mesothelial cells and peritoneal macrophages early in the course of peritonitis occurs via cell–cell interaction and secretion of various inflammatory mediators.56  Effects of Peritoneal Dialysis Solutions on Peritoneal Defense The effects of commercial PD solutions on peritoneal defense are related to dilution, high osmolality, low pH, lactate, and heat sterilization of the dialysate. In addition to the dilutional effects on intraperitoneal (IP) immunoglobulin and complement levels, decreased density of peritoneal macrophages reduces the phagocyte-bacterium encounter and thus bacterial killing.54 The high osmolality and low pH of dialysis solution suppress peritoneal PMN and macrophage functions.57 Although dialysate pH rises to physiological levels within 30 minutes of infusion, the period of low pH coincides with that of a high risk for bacterial entry. Lactate in dialysis solution may have independent adverse effects on peritoneal defense.58 Some studies showed that biocompatible PD solutions with normal pH and bicarbonate-buffer dialysis solution may reduce the risk for peritonitis.59,60 However, in vitro PMN function after incubation in bicarbonate-based dialysis solution also is impaired.61 A metaanalysis of six randomized controlled trials (RCTs) concluded that the use of neutral pH or bicarbonate-buffered PD solutions had no definite effect

CHAPTER 32  Peritoneal Dialysis-Related Infections on the rate of peritonitis.62 The effect of glucose polymer– based or other novel PD solutions on leukocyte function has not been well studied. 

Presentation Patients with peritonitis typically present with cloudy dialysis effluent and abdominal pain.63 Other common symptoms at presentation include diarrhea, vomiting, chills, and reduction in PD outflow. Although theoretically possible, abdominal pain with clear PD effluent seldom indicates peritonitis. A small but non-negligible group of patients present with cloudy PD effluent but no abdominal pain. The severity of illness varies widely and partly depends on the etiological microorganism.64 For example, S. epidermidis or diphtheroids often cause minimal abdominal pain. On the other hand, virulent organisms such as S. aureus, P. aeruginosa, and fungi often cause severe abdominal pain and, not uncommonly, diarrhea. Fever and hypotension indicate systemic sepsis, bacteremia, and severe peritonitis.64,65 

Diagnosis Most practicing nephrologists can diagnose PD-related peritonitis on clinical grounds. Nonetheless, a standard set of diagnostic criteria has been designed to facilitate dialysis unit audit and assist in making the diagnosis by nonspecialists. The latest ISPD guideline states that peritonitis should be diagnosed when at least two of the following are present: (1) clinical features consistent with peritonitis (i.e., abdominal pain and/or cloudy dialysis effluent); (2) dialysis effluent white cell count >100/μL or >0.1 × 109/L (after a dwell time of ≥2 hours), with >50% PMN; and (3) positive dialysis effluent culture.9 For patients receiving machine-assisted PD with rapid cycles, the PD effluent white blood cell (WBC) count may be <100/μL during peritonitis. In this circumstance, one should rely on the differential WBC count, and a PMN >50% is indicative of peritonitis. The differential diagnosis for infectious peritonitis includes chemical peritonitis, peritoneal eosinophilia, hemoperitoneum, pancreatitis, chylous effluent, and malignancy.66 Peritoneal eosinophilia usually occurs early in the course of PD, resolves spontaneously after 2 to 6 weeks, and is usually not associated with infection.67 The mechanism is believed to be allergic reaction to the plasticizers on the dialysis tubing. IP administration of amphotericin68 can cause chemical peritonitis. Sterile chemical peritonitis also has been reported after icodextrin PD solution.69 The episodes are characterized by mild abdominal discomfort, dialysate leukocytosis with a predominance of macrophages, and the absence of systemic symptoms. PD patients who develop pancreatitis may present with abdominal pain and cloudy dialysis effluent. Typically, culture of the effluent yields no bacterial growth, and the effluent amylase level is >100 U/L.70 Chylous ascites is a rare cause of sterile cloudy effluent, and the effluent WBC count is normal.71 Patients with intraabdominal malignancy may have cloudy effluent, and the diagnosis can be established by cytological evaluation.72 

511

Treatment of Peritonitis

Initial Evaluation PD patients presenting with cloudy effluent should be presumed to have peritonitis and should be treated as such until the diagnosis can be confirmed or excluded.9 In a patient presenting with possible peritonitis, evaluation should include questioning about possible touch contamination, adherence to sterile exchange technique, recent procedures that may lead to peritonitis, and change in bowel habits. A formal rootcause analysis is valuable in preventing further episodes of peritonitis, but it can be performed after the patient improves with treatment. The physician should review any history of recent peritonitis episode so as to determine the possibility of relapsing episode or antibiotic resistance. In addition to the usual physical examination, one must carefully search for coexisting ESI or tunnel infection. PD effluent should be tested for WBC count, differential, and Gram stain and should be cultured whenever peritonitis is suspected.9 Bloodculture bottle is the preferred technique for bacterial culture of PD effluent.9 At present, there is insufficient evidence to support the use of novel laboratory and molecular techniques for the diagnosis of peritonitis.9  Empirical Therapy As just emphasized, PD patients presenting with cloudy effluent should be presumed to have peritonitis, and empirical antibiotic therapy should be initiated as soon as possible after appropriate microbiological specimens have been obtained.9 Many patients with PD-related peritonitis could be managed on an outpatient basis. The decision to hospitalize a patient depends on clinical factors (e.g., severity of signs and symptoms) as well as practical ones (e.g., feasibility of administering IP antibiotics). The recommended treatment regimen has been described in detail by the latest ISPD guideline.9 In essence, empirical antibiotic regimens should be center-specific and cover both gram-positive and gram-negative organisms.9 Gram-positive organisms could be covered by vancomycin or a first-generation cephalosporin, whereas gram-negative organisms could be covered by a third-generation cephalosporin or an aminoglycoside.9 For gram-positive coverage, a metaanalysis showed that vancomycin-based regimens result in a higher complete cure rate than first-generation cephalosporin, but there is no difference in the rate of primary treatment failure, relapse, or catheter removal.73 Theoretical concern of inducing vancomycin resistance would favor the use of first-generation cephalosporin, except for PD units that have a high rate of methicillin-resistant organisms. For the coverage of gram-negative organisms, previous studies showed that aminoglycosides and third- or fourth-generation cephalosporins are equally effective74,75 Aminoglycosides are inexpensive, and there is no evidence that short courses of aminoglycosides accelerate the loss of residual renal function.76,77 However, repeated or prolonged aminoglycoside treatment (>3 weeks) is associated with a high incidence of vestibular and oto-toxicity and should be avoided.78 Table 32.2 summarizes the algorithm

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TABLE 32.2  Algorithm of the Initial Assessment and Therapy for Peritoneal Dialysis-Related

Peritonitis Goal Evaluation

Steps Clinical evaluation; examine exit site and catheter tunnel. Collect dialysis effluent for cell count, differential count, Gram stain, and bacterial culture.

Treatment

Start intraperitoneal antibiotics as soon as possible Allow to dwell for at least 6 h Empirical gram-positive and gram-negative coverage, based on patient history and center sensitivity patterns Gram-positive coverage: Gram-negative coverage: first-generation cephalosporin or vancomycin third-generation cephalosporin or aminoglycoside

Adjunctive measures

Consider adjuvant treatment: pain control; IP heparin; antifungal prophylaxis. Education and assess IP injection technique. Ensure follow-up arrangements.

IP, Intraperitoneal. Adapted from Li PK, Szeto CC, Piraino B, et al. ISPD peritonitis recommendations: 2016 update on prevention and treatment. Perit Dial Int. 2016;36:481-508.

BOX 32.1  Empirical Initial Therapy for

Peritoneal Dialysis-Related Peritonitis

Gram-positive coverage • Cefazolin • intermittent: 15–20 mg/kg IP daily • continuous: 500 mg/L IP loading, 125 mg/L IP maintenance • APD: 20 mg/kg IP daily in long day dwell • Vancomycin • intermittent: 15–30 mg/kg IP every 5–7 d • APD: as above, in long day dwell Gram-negative coverage • Ceftazidime • continuous: 500 mg/L IP loading, 125 mg/L IP maintenance • APD: 1000–1500 mg IP daily in long day dwell • Aminoglycoside (gentamicin/netilmicin/tobramycin) • intermittent: 0.6 mg/kg IP daily • APD: as above, in long day dwell APD, Automated peritoneal dialysis; IP, intraperitoneal. Adapted from Li PK, Szeto CC, Piraino B, et al. ISPD peritonitis recommendations: 2016 update on prevention and treatment. Perit Dial Int. 2016;36:481-508.

for the initial assessment and empirical antibiotic therapy of PD-related peritonitis. Suitable agents and dosages are listed in Box 32.1. In general, IP antibiotics are the preferred route of administration unless the patient has features of systemic sepsis.9 

Practical Aspects of Antibiotic Therapy For many antibiotics, IP regimen can be given as continuous (i.e., in each exchange) or intermittent dosing (i.e., once daily to once every few days). Because of its concentration-dependent bactericidal effect, IP aminoglycoside should preferably be administered as daily intermittent dosing.9 There is no evidence that monitoring aminoglycoside levels mitigates toxicity risk or enhances efficacy.79 IP vancomycin could be administered intermittently, usually at a dosing interval of

every 4 to 5 days.9 Redosing is probably appropriate to keep serum vancomycin levels >15 μg/mL.79 For cephalosporins, basic pharmacological principles would favor continuous dosing because this group of agent kills bacteria in a time-dependent manner. However, there are few data to support that continuous dosing is more efficacious than intermittent dosing. Moreover, intermittent dosing regimens are valuable in some situations. For example, some elderly or debilitated patients would require helpers or healthcare visitors for the administration of IP antibiotics, and intermittent dosage may be the only practical solution when the injection could only be performed once or twice daily and drug stability in PD solution is a concern. Intermittent dosage is also the only possible means of administering antibiotics for patients treated with machine-assisted PD. In this case, the intermittent IP dosing could be given in the day dwell.9 Because extrapolation of pharmacokinetic data from continuous ambulatory peritoneal dialysis (CAPD) to machine-assisted PD may result in significant underdosing when antibiotics are given IP intermittently, a higher daily dose often is required.9 Alternatively, patients on machine-assisted PD who develop peritonitis may temporarily switch to CAPD.9 However, it is not always practical to switch because patients may not be familiar with the exchange technique, and the supplies for CAPD may not be immediately available. 

Adjuvant Therapy Extensive rapid-cycle peritoneal lavage during the first 24 hours of peritonitis does not affect the clinical outcome and is not advisable for routine clinical use.80 Patients with cloudy PD effluent may benefit from the addition of IP heparin (e.g., 500 units/L) to prevent occlusion of the catheter by fibrin. Antifungal prophylaxis, preferably by oral nystatin, should be given during antibiotic therapy to prevent secondary fungal peritonitis.9,81 The benefit of IP urokinase for the treatment of relapsing or refractory peritonitis has not been confirmed.82,83

CHAPTER 32  Peritoneal Dialysis-Related Infections TABLE 32.3  Treatment Regimen for Gram-

Positive Peritonitis

Staphylococcus aureus

CoagulaseNegative Staphylococcus

Enterococcus At 24–48 h • Stop cephalo- • Stop ceftazidime • Stop ceftazidime sporins or aminoglycoor aminoglyco • Start IP vancoside, continue side, continue mycin IP cefazolin IP cefazolin • Consider • Consider adding • If methicillin adding IP oral rifampin resistant or cliniaminoglycoside 450–600 mg/d cally not respondfor 5–7 d ing, change to IP • If methicillin vancomycin resistant or clinically not responding, change to IP vancomycin Duration of Therapy • 21 d • 21 d

• 14 d

IP, Intraperitoneal. Adapted from Li PK, Szeto CC, Piraino B, et al. ISPD peritonitis recommendations: 2016 update on prevention and treatment. Perit Dial Int. 2016;36:481-508.

Because of the systemic inflammatory response and increased peritoneal protein loss, protein-energy wasting develops quickly during PD peritonitis. During peritonitis, ultrafiltration (UF) by PD is usually reduced. Protein-energy wasting should be screened for and appropriate supplement should be considered in patients with prolonged peritoneal inflammation. In patients with diabetes, glycemic control may worsen during peritonitis because of the rapid glucose absorption. Blood glucose monitoring with appropriate adjustments of insulin dosage may be needed. Fluid overload is a frequent complication, and the usual PD regimen may need to be adjusted according to the clinical condition. A recent study suggested that the use of icodextrin solution during acute peritonitis resulted in better UF and fluid control in CAPD patients.84 

Therapy for Specific Organisms Gram-Positive Microorganisms.  The treatment for gram-­ positive peritonitis is outlined in Table 32.3. Peritonitis episodes due to CNSS, S. aureus, Streptococcus, and Enterococcus species are distinctly different in presentation, pathogenesis, and outcome. Treatment must therefore be individualized.  Coagulase-Negative Staphylococcal Species Peritonitis episodes caused by CNSS should be treated with IP first-generation cephalosporins or vancomycin, according to the antimicrobial susceptibility, for 2 weeks.9 These episodes often are secondary to touch contamination. Exchange technique of the patient and adherence to aseptic technique should be checked. Nowadays, some centers have very high prevalence of methicillin resistance,85 and vancomycin may

513

need to be considered as empirical therapy. On the other hand, vancomycin may be slightly less effective than first-generation cephalosporins when the bacteria are methicillin-sensitive. Relapsing coagulase-negative staphylococcus peritonitis suggests colonization of the PD catheter with biofilm, and catheter removal should be considered. The benefit of IP urokinase and oral rifampicin for the prevention of relapsing episode remains controversial.86 

Staphylococcus aureus Peritonitis episodes caused by S. aureus should be treated with effective antibiotics for 3 weeks.9 These episodes often are secondary to ESIs or tunnel infections, which should be carefully searched for. Ultrasound study of the catheter tunnel may help to diagnose occult tunnel infections and identify a subgroup of patients who are likely to require catheter removal. Screening for nasal S. aureus carrier also should be considered, especially in patients with relapsing or repeated peritonitis episodes caused by S. aureus. Two retrospective studies found that the initial empiric antibiotic choice between vancomycin and cefazolin had similar clinical outcomes.87,88 One study showed that the use of adjuvant rifampicin for 5 to 7 days may reduce the risk for relapsing or repeat S. aureus peritonitis.87 However, rifampicin is a potent liver enzyme inducer and interaction with other concomitant medications may be problematic. For patients with concomitant S. aureus ESI or catheter tunnel infection, catheter removal should be considered.  Streptococcal Species Streptococci frequently originate from the mouth,89 although Streptococcus bovis typically comes from the colon.90 Peritonitis episodes caused by streptococci usually respond well to IP cefazolin or vancomycin treatment.81,89 Patients often are advised to wear a face mask during PD exchange to prevent further episodes of streptococcal peritonitis, but there is no published evidence to support this practice.  Enterococcus Species Peritonitis episodes caused by Enterococcus species are usually severe. In about half of the cases of enterococcal peritonitis, other coexisting organisms could be isolated, and intraabdominal pathology must be considered. Since enterococcal species have intrinsic resistance to cephalosporins, and ampicillin may be unstable in PD solution, enterococcal peritonitis should be treated with IP vancomycin for at least 3 weeks.9 IP aminoglycoside could be added as adjunct for severe cases.9 Treatment of peritonitis episodes caused by vancomycin-resistant enterococcus should be individualized. Linezolid, quinupristin/dalfopristin, daptomycin, or teicoplanin are all valid options. Gram-Negative Organisms.  Peritonitis due to gram-negative organisms often is associated with fever, nausea, vomiting, and abdominal pain. The treatment of gram-negative peritonitis is summarized in Table 32.4. Satisfactory therapeutic responses have been reported with either IP aminoglycoside or ceftazidime.91 Other third- or fourth-generation cephalosporins are

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TABLE 32.4  Treatment Regimen for Gram-

Negative Peritonitis Single GramNegative Organism At 24–48 h • Stop cefazolin or vancomycin • Continue IP ceftazidime or aminoglycoside • Adjust antibiotics according to sensitivity

Pseudomonas Species • Continue ceftazidime or aminoglycoside • Treat with both IP ceftazidime and IP aminoglycoside • Adjust antibiotics according to sensitivity

Duration of Therapy • 14–21 d • 21 d

Multiple GramNegative or Anaerobes • Stop cefazolin • Continue IP ceftazidime or aminoglycoside • Start IP vancomycin and oral or intravenous metronidazole • Consider surgical evaluation • 21 d

IP, Intraperitoneal. Adapted from Li PK, Szeto CC, Piraino B, et al. ISPD peritonitis recommendations: 2016 update on prevention and treatment. Perit Dial Int. 2016;36:481-508.

probably equally effective. Alternatively, fluoroquinolones, such as levofloxacin, ciprofloxacin, and moxifloxacin, have the advantage of good oral bioavailability, and can be used with acceptable result.92 

Pseudomonas Species Recent antibiotic therapy is the major risk factor of Pseudomonas peritonitis.93 Patients with immunosuppression are also at higher risk for Pseudomonas peritonitis.94 Pseudomonas peritonitis should be treated with two antibiotics (e.g., IP gentamicin or oral ciprofloxacin with IP ceftazidime or cefepime) for 3 weeks.9 When there is concomitant ESI or tunnel infection, catheter removal is usually necessary. In this circumstance, simultaneous removal and reinsertion of a new PD catheter (with a new tunnel and exit site) may avoid the need of temporary hemodialysis and often is successful in preventing further relapsing episodes.  Other Gram-Negative Bacteria Single-organism gram-negative peritonitis may be secondary to touch contamination, ESI, or transmural migration from constipation or colitis. In general, non-Pseudomonas gram-negative peritonitis should be treated with effective antibiotics for at least 3 weeks.9 A retrospective study suggests that treatment with two antibiotics may reduce the risk for relapse and recurrence compared with treatment by a single agent.95 In recent years, there has been an increase in incidence and probably recognition of peritonitis episodes caused by gram-negative bacilli with extended-spectrum beta-lactamases and carbapenem-resistant Enterobacteriaceae. Their treatment should be individualized. A number of new second-line antibiotics, such as ceftaroline, ceftolozane plus tazobactam, and tigecycline, are potentially effective.96 

Polymicrobial Peritonitis When multiple enteric organisms (multiple gram-negative or mixed gram-negative and gram-positive organisms) are grown from the PD effluent, it often indicates the presence of intraabdominal pathology. Treatment should include oral or intravenous metronidazole plus IP vancomycin and either IP aminoglycoside or IP ceftazidime for a minimum period of 3 weeks.9 Similarly, the presence of anaerobic bacteria or fungus as part of the mixed microbial growth from the PD effluent usually suggests underlying surgical pathology. On the other hand, if multiple gram-positive organisms are grown from PD effluent, intraabdominal pathology is less likely and the prognosis is usually favorable. These patients should be treated with effective antibiotics for 3 weeks.9 Routine surgical intervention for this group of patients is often not necessary. Culture-Negative Peritonitis.  In approximately 15% of episodes that meet the criteria for peritonitis on the basis of cell count and clinical features, culture of the PD effluent would not yield any pathogenic organisms. Most of the culture-negative peritonitis could be explained by recent antibiotic therapy or technical problems during the collection of PD effluent for culture.97 Negative PD effluent cultures on day 3 warrant a repeat dialysis effluent WBC count with differential.9 If the culture-negative peritonitis is resolving at that time, the empirical antibiotic that covers gram-positive organisms (i.e., first-generation cephalosporin or vancomycin) should be continued for 2 weeks, although it remains controversial whether the empirical antibiotic that covers gram-negative organisms should be stopped. In general, IP aminoglycoside should be discontinued to avoid extended or repeated exposure,9 whereas third-generation cephalosporins may be continued, especially in centers with a high background incidence of gram-negative peritonitis. If the culture-negative peritonitis is not resolving on day 3, special culture techniques should be considered for isolation of unusual organisms.9 Fungus and mycobacterial species may not be recovered by routine bacterial culture of PD effluent and should also be considered as the causative organisms. Fungus.  Fungal peritonitis occurs in patients undergoing PD at the rate of 0.01 to 0.19 episodes per dialysis-year, accounting for 3% to 6% of episodes.4,98,99 More than 70% of the episodes of fungal peritonitis are caused by Candida species.99,100 Recent antibiotic therapy, frequent episodes of bacterial peritonitis, and immunosuppression are the major risk factors of fungal peritonitis.101 Patients often are severely ill with marked abdominal tenderness.100,102 Catheter removal is indicated once fungi are identified in PD effluent, and an appropriate antifungal agent should be continued for at least 2 weeks after catheter removal.9 Traditionally, the therapy for fungal peritonitis is a combination of amphotericin B and flucytosine. However, this regimen has a high incidence of adverse effects, and the response often is less than satisfactory because amphotericin B has poor penetration through the peritoneal membrane. Fluconazole is commonly used for peritonitis episodes caused by many Candida species and Cryptococcus,103 but this agent is fungistatic. Echinocandins (especially caspofungin) is now

CHAPTER 32  Peritoneal Dialysis-Related Infections often advocated for the treatment of fungal peritonitis caused by Aspergillus species and nonalbicans Candida species,104 whereas posaconazole and voriconazole are reasonable choices for episodes caused by other filamentous fungi.105 However, it should be noted that intravenous voriconazole is contraindicated in dialysis patients because it contains cyclodextrin in the solvent and may cause neurotoxicity in patients with severe renal impairment.

Mycobacterial Peritonitis 

Tuberculous Peritonitis Tuberculous peritonitis is uncommon in the Western world, but is more common in Asian countries. Contrary to the common belief, the WBCs in the effluent, at least during the early phase of peritonitis, are predominantly PMN cells, and an acidfast bacilli stain of an effluent specimen is usually negative.106 Abnormal chest radiograph and ascitic fluid lymphocytosis only identify one-third of the cases.107 Conventional microbiological diagnostic methods are slow and have a low sensitivity. New fluid medium (e.g., Septi-Chek, BACTEC; Becton Dickinson) could reduce the time to develop and positive culture. Overall diagnostic yield could further be improved by centrifuging 50 to 100 mL effluent, followed by culturing the sediment in both solid and fluid media. Alternatively, mycobacterial DNA polymerase chain reaction can be performed on dialysis effluent, although false-positives are common.108 Peritoneal biopsy often is recommended for expedite diagnosis of tuberculous peritonitis in clinically suspicious cases, but this strategy is not practical for PD patients. Regarding the treatment, standard antituberculous chemotherapy is highly effective,106,107 but it takes at least 12 months to complete the course. Drug interactions between rifampicin and other concomitant medications are common. Removal of PD catheter is usually not necessary, but UF problems may occur as a delayed complication.109  Nontuberculous Mycobacterial Peritonitis In subtropical countries, there is an increase in incidence of peritonitis caused by nontuberculous mycobacteria in the past decade.110,111 More than half of the cases are caused by rapidly growing species, such as Mycobacterium fortuitum and M. chelonae.110 It has been postulated that extensive use of topical antimicrobial ointment (especially gentamicin) for exit-site care may predispose patients to nontuberculous mycobacterial infection of the exit site.112 The treatment regimen for nontuberculous mycobacterial peritonitis is not well established, but catheter removal is usually necessary.9  Reassessment After Therapy Most patients with PD-related peritonitis show considerable clinical improvement after 2 to 3 days of antibiotic therapy. Antibiotic therapy should be adjusted to narrow spectrum agents, as appropriate, once culture results and sensitivities are known. If the patient has not shown definitive clinical improvement after 3 days of empirical therapy, effluent cell counts, Gram stain, and cultures should be repeated. PD effluent WBC count ≥1090/mm3 on day 3 predicts treatment

515

TABLE 32.5  Terminology of Peritonitis Recurrent

Relapsing

Repeat

Refractory

An episode that occurs within 4 wk of completion of therapy of a prior episode but with a different organism. An episode that occurs within 4 wk of completion of therapy of a prior episode with the same organism or one sterile episode. An episode that occurs >4 wk after completion of therapy of a prior episode with the same organism. Failure of the effluent to clear after 5 d of appropriate antibiotics.

Adapted from Li PK, Szeto CC, Piraino B, et al. ISPD peritonitis recommendations: 2016 update on prevention and treatment. Perit Dial Int. 2016;36:481-508.

failure.113 Theoretically, catheter removal should be considered if the response to antibiotic therapy is poor after 4 days of antibiotic therapy (see next section), but this recommendation is difficult to follow in practice as it is limited by the availability of surgeon, operating theatre, as well as patients’ own preference. 

Catheter Removal The definitions of refractory, relapsing, recurrent, and repeat peritonitis are summarized in Table 32.5. PD catheter should be removed promptly in refractory peritonitis.9 Timely catheter removal also should be considered for relapsing peritonitis, refractory ESI and tunnel infection, and fungal peritonitis.9 In most patients, temporary hemodialysis is needed after catheter removal. However, simultaneous removal and reinsertion of catheters is a safe and effective method for the treatment of refractory ESI114 as well as for the prevention of relapsing peritonitis after dialysis effluent clears up.115,116 Effective systemic antibiotics should be continued for at least 2 weeks after catheter removal for peritonitis.9 Insertion of a new PD catheter could be attempted at least 2 weeks after catheter removal and complete resolution of peritoneal symptoms.9 Reinsertion should be done by laparoscopic or minilaparotomy approach so that adhesion can be directly visualized. In about 50% of the patients who have had their catheter removed, PD can be successfully resumed,117,118 but UF problems are common subsequently.117 Peritoneal equilibration test should be considered around 1 month after resuming PD for the tailoring of PD regime. 

Complications of Peritoneal Dialysis Peritonitis Peritonitis results in a marked increase in dialysis effluent protein losses, which may aggravate the protein-energy wasting of PD patients.119 Attention should particularly be paid on the nutritional status of patients with prolonged peritoneal inflammation. Reduction in UF is common during peritonitis episodes because peritoneal permeability is increased.120 The use of hypertonic exchanges and short dwell times may be needed during this period to maintain adequate fluid removal, but appetite may be further worsened with this approach. Temporary use of icodextrin solution may prevent

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TABLE 32.6  Exit-Site Scoring System Swelling

0 Points No

Crust Redness Pain Drainage

No No No No

1 Point Exit only; < 0.5 cm <0.5 cm <0.5 cm Slight Serious

2 Points >0.5 cm or involve tunnel >0.5 cm >0.5 cm Severe Purulent

Catheter-related infection is diagnosed if score ≥4. Modified from Schaefer F, Klaus G, Müller-Wiefel DE, Mehls O. Intermittent versus continuous intraperitoneal glycopeptide/ceftazidime treatment in children with peritoneal dialysis-associated peritonitis. J Am Soc Nephrol. 1999;10:136-145.

fluid overload in PD patients with acute peritonitis, and the therapeutic response is not affected.84 Because of rapid glucose absorption, glycemic control may worsen during peritonitis in patients with diabetes. Blood glucose monitoring with appropriate adjustments of insulin dosage may be needed. The change in the peritoneal permeability during peritonitis is usually transient.121 However, after multiple peritonitis episodes or an episode of severe peritonitis, permanent increase in solute transport and loss of UF capability may occur.117,122 The risk is probably proportional to the extent of inflammation and the number of peritonitis episodes.123 The final stage of this process is peritoneal fibrosis, sometimes referred to as encapsulating peritoneal sclerosis (EPS).122 EPS is present in approximately 1% of patients undergoing PD and is possibly more common in some countries (e.g., Japan).124 In addition to UF failure, the EPS patient becomes progressively malnourished because of recurrent partial intestinal obstruction from encasement of the bowel. PD cannot be continued and this complication is frequently lethal despite conversion to long-term hemodialysis. 

CATHETER-RELATED INFECTIONS CRIs are used as the collective term to describe ESI and tunnel infection. These two entities may occur on their own or simultaneously. Bacterial colonization of the PD catheter exit site may lead to infection of the catheter exit site, which may further spread along the subcutaneous tunnel of the catheter to the inner cuff and subsequently to the peritoneum, resulting in tunnel infection and peritonitis, respectively. The reported incidence of CRIs, as well as the prevalence of individual causative organism, varies considerably in the literature,125,126 but for most PD centers, S. aureus and P. aeruginosa are the most common causes of CRIs.

Definitions ESI is defined as the presence of purulent discharge, with or without erythema of the skin at the catheter-epidermal interface.10 The classification of catheter exit-site appearance is summarized in Table 32.6.127 Peri-catheter erythema without purulent drainage is sometimes an early indication of infection, but also can be an allergic skin reaction, or in a recently placed catheter or after trauma to the catheter.128

Catheter tunnel infection is defined as the presence of clinical or ultrasonographic evidence of inflammation or collection along the catheter tunnel.10 Tunnel infections are commonly occult, and often only detected by ultrasonography of the subcutaneous catheter tunnel.19,129 ESI caused by S. aureus or P. aeruginosa often are associated with concomitant occult tunnel infections.130 

Risk Factors The major risk factor in S. aureus catheter infections is nasal carriage of S. aureus,131,132 which is present in around 50% of new and prevalent PD patients.132 Patients who were S. aureus carriers had significantly higher incidences of S. aureus ESIs, tunnel infections, and peritonitis than noncarriers.131,132 Only 33% of the S. aureus carriers had the same phage type upon repeat culture, and 16% patients are intermittent carriers only.132 ESI, especially episodes caused by S. aureus and P. aeruginosa, is the major risk factor for tunnel infection. In addition, tunnel infections are probably more common in patients with diabetes.130 Immunosuppressed patients are at increased risk for catheter infections.133 A downward-directed catheter exit site is associated with easier-to-treat infections, with fewer episodes of catheter-related peritonitis.1 

Treatment

Clinical Presentation and Assessment ESI generally presents as purulent drainage from the exit site, with or without surrounding erythema. Tunnel infection, if clinically apparent, usually presents as erythema, edema, induration or tenderness over the subcutaneous pathway, and often occurs in the presence of ESI. Peri-catheter erythema without purulent drainage could be an early sign of ESI but also can be a local skin reaction without infection. Gram stain of exit-site drainage and bacterial culture with aerobic and anaerobic media are valuable to guide the treatment. A review of the previous bacterial culture from exit-site swab often gives valuable information in guiding the choice of antibiotics for patients presenting with ESI or tunnel infection.  Exit-Site Care During an episode of acute CRI, the exit site should be cleansed at least daily.10 However, there is no published trial on the efficacy of intensified exit-site care for the treatment (not prevention) of overt CRIs,50,51 and the choice of the optimal cleansing agent has not been defined. Although commonly used, there are few data on the efficacy of topical antibacterial agents in the treatment of active CRIs.134  Antibiotic Therapy When a clinical diagnosis of ESI or tunnel infection is made, empiric oral antibiotic treatment with appropriate S. aureus cover, such as a penicillinase-resistant penicillin (cloxacillin, dicloxacillin, or flucloxacillin) or first-generation cephalosporin, are reasonable choices.10 If the patient has a history of infection or colonization with methicillin-resistant S. aureus (MRSA), empirical therapy with a glycopeptide

CHAPTER 32  Peritoneal Dialysis-Related Infections TABLE 32.7  Recommended Dosage of

Common Oral Antibiotics for CatheterRelated Infections Amoxicillin Amoxicillin/clavulanic acid Ciprofloxacin Cloxacillin/flucloxacillin Levofloxacin Trimethoprim/sulfamethoxazole

250–500 mg bid 875 mg/125 mg bid 250 mg bid or 500 mg/d 500 mg QID 300 mg/d 80 mg/400 mg/d to 160 mg/ 800 mg bid

bid, Twice a day; QID, four times a day. From R Gokal, Ash SR, GB Helfrich, et al. Peritoneal catheters and exit-site practices: toward optimum peritoneal access. Perit Dial Int. 1993;13:29-39; Zimmerman SW, O’Brien M, et al. Randomized controlled trial of prophylactic rifampin for peritoneal dialysis-related infections. Am J Kidney Dis. 1991;18:225-231; lowey DL, Warady BA, McFarland KS. The treatment of Staphylococcus aureus nasal carriage in pediatric peritoneal dialysis patients. Adv Perit Dial. 1994;10:297-299. Hardy DJ, Guay DR, Jones RN. Clarithromycin, a unique macrolide. A pharmacokinetic, microbiological, and clinical overview. Diagn Microbiol Infect Dis. 1992;15:39-53.

or clindamycin should be considered.10 Similarly, if there is a past history of CRI or peritonitis caused by Pseudomonas species, empirical therapy with a fluoroquinolone or thirdor fourth-generation cephalosporins may be preferred. Oral antibiotics appear to be as efficacious as parenteral agents.134 The recommended dosage for commonly used oral antibiotics are summarized in Table 32.7. When the result of Gram stain or culture becomes available, the oral antibiotic regimen should be tailored according to the specific organism identified. S. aureus catheter infections often respond to penicillinase-resistant penicillin, first-generation cephalosporin, or trimethoprim-sulfamethoxazole.134,135 Rifampin may have activity within bacterial biofilm and can be used as adjunctive therapy, although there is no prospective study to support the benefit of this practice. Potential interaction with other concurrent medications (e.g., antihypertensive agents) also should be considered during rifampicin treatment. ESI caused by Pseudomonas species preferably should be treated with two antibiotics.10 Patients should be reviewed regularly to determine the clinical response to treatment. Most ESIs should be treated with at least 2 weeks of effective antibiotics.10 However, tunnel infections and ESI caused by Pseudomonas species should be treated with at least 3 weeks of effective antibiotics.10 Repeating exit-site wound swab for bacterial culture after the discontinuation of antibiotic treatment probably is not necessary. Ultrasonography of the catheter tunnel also has been advocated for evaluating the response to therapy, and may be used to decide on the need for surgical intervention.135,136 

Catheter Removal The PD catheter should be removed in patients with ESI that progresses to, or occurs simultaneously with, peritonitis. These patients should receive temporary hemodialysis, and reinsertion of a PD catheter could be considered at least 2

517

weeks after catheter removal and complete resolution of peritoneal symptoms.10 On the other hand, simultaneous removal and reinsertion of the dialysis catheter with a new exit site under antibiotic coverage could be considered in patients with refractory ESI or tunnel infection without peritonitis,10 or, when there is concomitant peritonitis, after the PD effluent has cleared up with IP antibiotics. Refractory ESI or tunnel infections are usually defined as failure to respond after 3 weeks of effective antibiotic therapy. 

Other Catheter Interventions Observational data suggest that partial catheter reimplantation137 and catheter diversion procedure with exit-site renewal138,139 could be considered for catheter salvage in refractory CRIs. In selected cases, cuff-shaving under systemic antibiotic cover may be considered as the alternative to catheter replacement for tunnel infection.140 The unroofing technique, with or without en bloc resection of the skin and tissues around the peripheral cuff, has been advocated. However, the procedure is associated with a risk for immediate peritonitis and also should be performed with systemic antibiotic coverage.141,142 

PREVENTION CRIs are major predisposing factors to PD-related peritonitis.89 The primary objective of preventing ESIs and tunnel infections is to prevent peritonitis. Many prevention strategies aim primarily at reducing the incidence of peritonitis, and clinical trials in this area often report the rate of ESIs or CRIs as a secondary outcome.

Catheter Design and Insertion Detailed description on the recommended practice of PD catheter insertion has been covered in a recent ISPD position paper.90 RCTs consistently show that prophylactic systemic antibiotics before the placement of PD catheter reduces the risk for early peritonitis and probably CRIs.81 Although first-generation cephalosporin may be slightly less effective than vancomycin in this regard, the former should be the agent of choice because of the concern of inducing vancomycin resistance.9 In addition to prophylactic antibiotics, the design and insertion technique of the PD catheter have little effect on the risk for peritonitis or CRIs. Specifically, there is no consistent difference in peritonitis risk between laparoscopic and minilaparotomy catheter placement, midline and lateral incisions, single and double cuff, straight and coiled catheter, or downward and lateral facing exit site.143 Novel designs such as buried catheter or presternal and abdominal swan neck catheters have other practical advantages but do not consistently lead to a lower infection rate.  Connectology and Dialysis Solutions For CAPD, prospective studies consistently show that disconnect systems with a “flush-before-fill” design result in a lower peritonitis rate than traditional spike systems144 and should

518

SECTION III  Dialysis

be used whenever available. The use of disconnect systems, however, has become the routine practice and spike systems are no longer available, at least in most developed countries. There is no significant difference between various disconnect systems (e.g., double bag and standard Y systems) in terms of peritonitis rate.144 Some data suggest that PD solutions with low glucose degradation product are associated with a lower risk for peritonitis.60 However, the results of published trials are not consistently positive.62 The latest ISPD guideline does not have any specific recommendation on the choice of PD solution in relation to the prevention of peritonitis.9 

Training and Continuous Quality Improvement Programs The training program of PD patients has an important influence on the risk for peritonitis and catheter infections.145 High-quality evidence that guides how, where, when, and by whom PD training should be performed, however, is lacking145 In general, the latest ISPD recommendations for teaching PD patients and their caregivers should be followed.146 In addition to the initial training, home visits by PD nurses, usually shortly after the patient returns home for regular PD, often are useful in detecting practical problems.147 Retraining in selected patients may reduce the risk for peritonitis. However, the indication of retraining is not well defined. The latest ISPD guideline recommends retraining after peritonitis or catheter infection; prolonged hospitalization; change in dexterity, vision, or mental acuity; change to another supplier or a different type of connection; or other interruption in PD.9 It also has been suggested by some experts that regular retraining may be beneficial. However, published evidence in this regard is lacking. The optimal frequency of routine retraining has not been generally agreed on, and the impact on nursing manpower should be considered. In addition to a formal patient training program, a continuous quality improvement program within a PD unit may help reduce the rate of peritonitis.148 The latest ISPD guideline recommends that multidisciplinary teams running continuous quality improvement programs in PD centers should meet and review their units’ performance metrics regularly.9  Exit-Site Care There is a strong association between ESIs and subsequent peritonitis.149 Early detection and prompt management of ESIs are logical steps to reduce the risk for subsequent peritonitis. During patient training, education on exit-site care and meticulous hand hygiene should be emphasized. The exit site should be cleansed at least twice weekly and every time after a shower.10 In countries with a hot and humid weather, daily exit-site cleansing may be necessary. Gauze is commonly used for exit-site dressing and protection, and immobilization of the catheter often is recommended, but there is no published evidence to support this kind of practice. A number of topical cleansing agents have been tested for the prevention of CRIs, but none has been shown to be superior with respect to preventing them.10 Antibacterial

soap and water are commonly used to clean the exit site but that efficacy has not been proved. Povidone-iodine, chlorhexidine, and electrolytic chloroxidizing solutions also are widely used. However, a systematic review shows that topical povidone-iodine disinfection does not reduce the risk for peritonitis compared with simple soap and water cleansing or no treatment.150 We believe chlorhexidine solution may be a better choice for exit-site cleansing. Contrary to exit-site cleansing and dressing, a good body of published evidence shows that daily use of topical mupirocin cream or ointment to the catheter exit site could effectively reduce the incidence of peritonitis.9,151 Once-weekly topical mupirocin is less effective than more frequent administration.152 Intranasal mupirocin reduced S. aureus ESIs but not peritonitis, and is less well tolerated by patients.153,154 Daily application of gentamicin cream is an acceptable alternative to mupirocin.9 Gentamicin cream application to the exit site is effective in reducing the risk for peritonitis, and has the additional advantage of reducing ESI caused by Pseudomonas species.155 The potential risk for resistance to mupirocin and gentamicin has always been a concern but the clinical ramifications remains unclear. The association between gentamicin cream and nontuberculous mycobacterial infection of the exit site has been suspected but never proved. Despite the initial enthusiasm, topical application of antibacterial honey or polysporin triple ointment were not found to be superior to conventional exit-site care.156,157 Other alternative topical antibacterial agents have been tested but none has gained wide acceptance for routine clinical use.9 

Management of S. aureus Carrier Nasal carrier of S. aureus is an important risk factor of CRIs. Although the evidence to support routine screening of nasal S. aureus carriage in PD patients is limited, the efficacy of prophylactic intranasal antibiotics, especially intranasal mupirocin, for the treatment of confirmed cases of nasal carriage of S. aureus has been shown to reduce the risk for CRIs.153 The effect on reducing peritonitis rate, however, is less clear. Cyclical oral rifampicin therapy (typically one 5-day course every 3 months) is effective in reducing the rate of CRIs, presumably by eradicating S. aureus carriage.158 Nonetheless, the routine use of oral rifampicin for the treatment of nasal S. aureus carrier or prevention of peritonitis is not recommended because adverse reactions, drug interactions, and rifampicin resistance are all common and important problems.10  Other Modifiable Risk Factors Peritonitis commonly follows invasive interventional procedures (e.g., colonoscopy, hysteroscopy, cholecystectomy) in PD patients. Observational data showed that prophylactic antibiotics before most endoscopic interventions, including colonoscopy, sigmoidoscopy, and invasive gynecological procedures (but not upper gastrointestinal endoscopy) were associated with a lower peritonitis rate.159 The optimal antibiotic regimen, however, has yet to be defined. A previous systematic review recommended the use of intravenous ampicillin plus an aminoglycoside, with or without metronidazole, for

CHAPTER 32  Peritoneal Dialysis-Related Infections this purpose.81 In our own experience, a single dose of amoxicillin/clavulanic acid or third-generation cephalosporins (e.g., cefotaxime) are convenient and effective alternatives. Common clinical sense suggests that prophylactic antibiotics should be used after wet contamination.9 There is no widely accepted standard regimen, but a 2-day course of fluoroquinolone is a reasonable regimen. Hypokalemia should be treated, partly because it is associated with an increased risk for enteric peritonitis.160 Pets should not be allowed where the PD procedure is being performed.161 A number of other modifiable risk factors for PD peritonitis have been described,162 but it remains unknown whether treating these risk factors would reduce the risk for peritonitis. 

Secondary Prevention of Peritonitis Most fungal peritonitis episodes are preceded by antibiotics treatment.163 Prophylactic treatment with either oral nystatin or fluconazole during systemic antibiotic therapy, especially when used for the treatment of bacterial peritonitis, significantly reduces the risk for secondary fungal peritonitis.81,164 Nystatin is generally the agent of choice because it is cheap and has no systemic effect. However, nystatin is not available

519

in some countries. In some centers, nystatin is only available as a mouthwash solution; patients need to be reminded to swallow the solution to ensure the efficacy of prophylaxis. Although fluconazole is effective, interaction with other concomitant medications is common, and the possibility of inducing resistant strains should be considered. For each peritonitis episode, a root-cause analysis should be performed to determine the etiology and contributing factors. Whenever possible, interventions directed against any reversible risk factor should be made to prevent further peritonitis episodes. The PD exchange technique should be reviewed (especially after an episode of gram-positive peritonitis), and focused retraining may be needed. Replacement of the catheter is more effective than urokinase in preventing further peritonitis episodes due to biofilm or bacterial adherence to the catheter, and should be considered in patients with relapsing or repeat peritonitis.73 In this scenario, catheter removal and reinsertion can be performed as a single procedure without the need for temporary hemodialysis after PD effluent has cleared up with antibiotic treatment.165 A full list of references is available at www.expertsonsult.com.

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