INTRODUCTION — Peritonitis is one of the major complications of peritoneal dialysis and remains the primary reason that patients switch from peritoneal dialysis to hemodialysis [1,2]. This topic reviews the microbiology and therapy of peritonitis in peritoneal dialysis. Risk factors, prevention, and the approach to the diagnosis of peritonitis, including exclusion of other intra-abdominal diseases, are discussed separately:
●(See "Risk factors and prevention of peritonitis in peritoneal dialysis".)
●(See "Clinical manifestations and diagnosis of peritonitis in peritoneal dialysis".)
MICROBIOLOGY — The vast majority of peritonitis cases are caused by bacteria. Approximately 3 to 5 percent are caused by fungi, mostly Candida spp [3-5]. A viral etiology of peritonitis has been postulated in some cases, although viral infection as a cause of peritonitis has not been proven conclusively [6].
Approximately 45 to 65 percent of cases are caused by gram-positive organisms and 15 to 35 percent by gram-negative organisms [4,5,7-10]. More than one organism has been reported in 1 to 4 percent of cases [3,4]. (See 'Polymicrobial peritonitis' below.)
Failure to identify an organism is common. Two series reported 20 to 40 percent of cases that were culture negative [3,4,11]; in the later series, the high percentage may have reflected failure to obtain a peritoneal dialysate sample prior to initiation of antibiotic treatment [4] (See 'Culture-negative peritonitis' below.)
The most common source of peritonitis is intraluminal contamination; typically, this occurs if the patient uses suboptimal sterile technique for connecting or disconnecting the catheter when performing exchanges ("touch contamination"). Other sources of peritonitis include periluminal contamination (due to extension of bacteria from an exit-site or tunnel infection), visceral contamination (via bacteria from bowel), and, rarely, vaginal contamination. In addition, peritonitis can develop via hematogenous dissemination from a remote source.
Specific pathogen categories are discussed in greater detail below:
●Gram positive – Common gram-positive pathogens include coagulase-negative Staphylococcus spp, Streptococcus spp, Staphylococcus aureus, Enterococcus spp, and Corynebacterium spp.
Coagulase-negative Staphylococcus is the most common cause of peritonitis. In one of the more recent studies, coagulase-negative staphylococci caused 60 percent of infections caused by gram-positive organisms and 39 percent of infections overall [10]. Streptococcus spp caused 20 percent of gram-positive infections and 13 percent of infections overall. S. aureus, Enterococcus spp, and Corynebacterium spp caused 6, 6, and 4 percent of gram-positive infections, respectively, and 4, 4, and 2.5 percent of infections overall.
The relative percentages of peritonitis caused by different Staphylococcus spp have changed over time [4,9]. The use of Y systems (or flush before fill) reduced the overall incidence of peritonitis [12,13], predominantly by decreasing touch contamination-associated infections due to coagulase-negative staphylococcus [4]. Because Y systems did not reduce the incidence of S. aureus peritonitis to the same degree, the relative proportion of staphylococcal peritonitis cases due to S. aureus increased.
The frequency of vancomycin-resistant enterococci (VRE) has increased [14]. Major risk factors include prior exposure to vancomycin and cephalosporins. (See "Vancomycin-resistant enterococci: Epidemiology, prevention, and control".)
●Gram negative – Gram-negative organisms can be from the bowel, skin, urinary tract, contaminated water, or animal contact [15,16]. In some centers, effective measures to prevent touch contamination and reduce the incidence of peritonitis cases caused by gram-positive organisms have led to an increase in the relative proportion, but not incidence, of peritonitis cases caused by gram-negative organisms [17]. (See "Risk factors and prevention of peritonitis in peritoneal dialysis", section on 'Prevention' and "Peritoneal catheter exit-site and tunnel infections in peritoneal dialysis in adults", section on 'Prevention'.)
Common causes of gram-negative peritonitis include Escherichia coli, Klebsiella spp, and Pseudomonas aeruginosa (33, 25, and 12 percent of the gram-negative infections in one study, respectively) [10].
●Fungal – Fungal peritonitis is uncommon in peritoneal dialysis patients. The presenting signs and symptoms associated with fungal peritonitis are similar to those seen with bacterial peritonitis. The approach to such patients is discussed separately. (See "Fungal peritonitis in peritoneal dialysis".)
Fungal infection is an indication for immediate catheter removal. (See 'Indications for catheter removal' below.)
DETERMINING THE SITE OF CARE — Most patients with peritoneal dialysis-associated peritonitis should be managed in the outpatient setting (algorithm 1). Indications for inpatient treatment include the following:
●Sepsis
●Severe abdominal pain
●Inability to administer intraperitoneal antibiotic therapy at home
●Unavailability of appropriate antibiotic agents in the outpatient setting
ANTIMICROBIAL THERAPY — The major treatment for peritoneal dialysis-associated peritonitis is antimicrobial therapy. Antibiotic treatment recommendations are based on expert opinion; systematic reviews have shown no single, optimal antibiotic agent or combination of agents [18,19].
Route of administration
Intraperitoneal administration (preferred) — Intraperitoneal administration of antibiotics is preferred to intravenous administration, unless the patient appears septic or has other indications for systemic antibiotics, as discussed below [20-22]. (See 'Oral or intravenous administration' below.)
Intraperitoneal administration provides optimal local antibiotic concentration. In the majority of patients, infection is localized to the peritoneum and a few cell layers lining the peritoneal cavity and intra-abdominal viscera. Commonly used antibiotics, including vancomycin, cephalosporins, and aminoglycosides, can be mixed in the same dialysis bag without loss of bioactivity.
●Continuous versus intermittent dosing – Intraperitoneal antibiotics can be administered either continuously (with antibiotics given in each exchange) or intermittently (given once daily for almost all antibiotics, with a few exceptions where every other bag dosing is recommended). We initiate therapy with intermittent dosing for ease-of-use reasons, though occasionally switch to continuous dosing if the patient does not respond to intermittent dosing (see 'Monitoring clinical response' below). However, many clinicians initiate therapy with continuous dosing. Continuous and intermittent intraperitoneal dosing regimens have similar rates of treatment failure and relapse [18].
Intraperitoneal antibiotics that are administered intermittently must dwell for at least six hours (table 1 and table 2). For patients on continuous ambulatory peritoneal dialysis (CAPD), intermittent antibiotics are typically administered during the overnight dwell, whereas for patients on automated peritoneal dialysis (APD) intermittent antibiotics are administered during the longest daytime dwell.
●Considerations for APD – Specific considerations apply to patients on APD. When patients set up their cycler, they will connect two or three bags of fluid for the overnight dwells, some of which may be used for the daytime dwell(s), and then often attach a different bag of fluid to be used for the daytime dwell(s). The typical daytime dwell often uses a different dialysate bag (different percent dextrose or icodextrin) than the overnight dwells. As a result, if the clinician is prescribing intermittent dosing, then the prescribed antibiotic should be added to the daytime dwell that is intended to dwell at least six hours. If the clinician wishes to use continuous dosing, the clinician and home training team need to remember that after the first overnight fill, the cycler draws fluid from all the overnight bags. Thus, when continuous dosing in APD is used, it is important to add antibiotics in the dose concentration (usually dosed in mg/L (table 1 and table 2)) to all bags.
Oral or intravenous administration — For patients with sepsis, bacteremia, or a visceral source of infection (eg, intra-abdominal process), intravenous antibiotics are usually necessary. Intravenous administration is also appropriate for initial therapy when immediate administration of intraperitoneal antibiotics is not possible, with a transition to intraperitoneal route once available. (See 'Timing' below.)
Oral or intraperitoneal antibiotics can be used as step-down therapy for patients on intravenous antibiotics once they have stabilized. Oral antibiotics can also be used when intraperitoneal administration of the necessary antibiotic is not an option.
For patients whose peritonitis is treated with systemic antibiotics (ie, oral or intravenous), concomitant intraperitoneal antibiotic administration is typically unnecessary.
Monitoring drug levels — For vancomycin and aminoglycosides, we typically monitor serum drug levels to facilitate dosing and prevent toxicity since systemic absorption occurs with intraperitoneal antibiotic administration. Monitoring serum levels of these antibiotics may be especially useful in patients with greater degrees of residual kidney function who may excrete substantial amounts of these agents in the urine.
However, this practice is not universal, and some clinicians do not monitor drug levels.
Role of antifungal prophylaxis — Treatment with intraperitoneal or systemic antibiotics is a major risk factor for the development of fungal peritonitis among peritoneal dialysis patients. (See "Fungal peritonitis in peritoneal dialysis", section on 'Causes and risk factors'.)
Antifungal prophylaxis during the course of antibiotic therapy may reduce the risk of subsequent fungal peritonitis. There is no consensus on the optimal approach to prevention of fungal peritonitis [23]. We administer antifungal prophylaxis among patients on peritoneal dialysis who are treated with antibiotics for longer than three days, regardless of the site of infection. However, others favor administration of antifungal prophylaxis with any antibiotic course lasting longer than one day [24-31]. (See "Fungal peritonitis in peritoneal dialysis".)
Issues related to selection and dosing of antifungal prophylaxis are discussed separately. (See "Fungal peritonitis in peritoneal dialysis", section on 'Prevention'.)
Initial empiric therapy — The initial empiric antibiotic regimen should be selected based on local sensitivity data for organisms that commonly cause peritonitis [22,32,33] and whether a patient has recently received antimicrobial therapy for another indication. Past culture results, including cultures from sites other than peritoneal fluid, should also be reviewed to assess whether a broader regimen is appropriate.
Timing — Empiric antibiotics should be initiated as soon as possible after peritoneal fluid specimens are obtained for cell count, Gram stain, and culture (algorithm 1) [22]. Most patients with peritonitis should be treated with intraperitoneal antibiotics (see 'Route of administration' above); however, in cases where the immediate administration of intraperitoneal antibiotics may not be possible (eg, in an emergency department or inpatient setting lacking staff trained in peritoneal dialysis), intravenous antibiotics should be administered to avoid lengthy delays in treatment. Patients with peritonitis receiving intravenous antibiotics due to anticipated delays in intraperitoneal antibiotic delivery should be switched from intravenous to intraperitoneal antibiotics as soon as it is feasible to do so. (See 'Oral or intravenous administration' above.)
The importance of prompt antibiotic administration was illustrated by an observational study of 116 patients with peritoneal dialysis-associated peritonitis [34]. In patients who presented to the hospital with peritonitis, every hour of delay in administering antimicrobial therapy was associated with a 6.8 percent increase in the risk of peritoneal dialysis failure or death.
Selection of empiric antibiotics — For initial therapy, we treat with a broad-spectrum antibiotic regimen that covers both gram-positive and gram-negative organisms [20-22,35]. As described above, we provide antifungal prophylaxis to patients who receive antibiotics for longer than three days. (See 'Role of antifungal prophylaxis' above.)
Preferred regimen — We generally use the following antibiotic regimen for initial empiric therapy (table 3):
●Intraperitoneal vancomycin plus intraperitoneal ceftazidime (see tables for dosing (table 1 and table 2))
However, prior to initiating empiric antibiotics, patients’ past culture results should be reviewed to assess whether a broader regimen is appropriate. (See 'Alternative regimens' below.)
For gram-positive coverage, we typically use intraperitoneal vancomycin because the majority of coagulase-negative staphylococci are resistant to beta-lactams and because vancomycin covers methicillin-resistant S. aureus (MRSA), a pathogen that has been associated with worse outcomes [36,37]. However, in centers where MRSA rates are low, some experts suggest that intraperitoneal cefazolin can be used instead of vancomycin since many coagulase-negative staphylococci reported as resistant to beta-lactams may be susceptible at the high cefazolin concentrations achieved in peritoneal fluid [22].
Alternative regimens — Alternative empiric regimens may be necessary due to antibiotic intolerance or suspicion of an antibiotic-resistant organism. Intraperitoneal dosing of these regimens is listed in the tables (table 1 and table 2).
For gram-positive coverage, intraperitoneal vancomycin is usually adequate. However, for patients with prior vancomycin-resistant enterococcal infection, intravenous daptomycin, or oral or intravenous linezolid, is appropriate.
For gram-negative coverage, we favor intraperitoneal ceftazidime because it has been shown to be effective in numerous studies, including studies of patients on CAPD and APD. Empiric intraperitoneal cefepime has been shown to be noninferior to standard of care in two small, randomized studies comparing outcomes of cefepime monotherapy with cefazolin plus ceftazidime and vancomycin plus netilmicin, but we continue to use ceftazidime because of the volume of evidence supporting it use [22,38,39]. Other cephalosporins (eg, ceftriaxone, cefazolin) have a narrower gram-negative spectrum than ceftazidime and cefepime (eg, ceftriaxone does not cover Pseudomonas spp).
If prior culture results suggest that an infection due to a multidrug-resistant gram-negative organism (eg, extended-spectrum beta-lactamase [ESBL]-producing bacteria) is possible, cephalosporins are often not appropriate. Other options include intraperitoneal carbapenems (eg, meropenem), oral or intraperitoneal fluoroquinolones (eg, ciprofloxacin), or intraperitoneal aminoglycosides (eg, gentamicin) (table 3). These antibiotics are also often options in patients who report serious penicillin allergies, although cephalosporins can often be safely administered to these patients. (See "Choice of antibiotics in penicillin-allergic hospitalized patients".)
Despite the convenience of oral dosing of fluoroquinolones, we generally try to avoid fluoroquinolones because they have significant adverse effects, increase the risk of Clostridioides difficile infection, and have numerous drug interactions (including oral phosphate binders) [40]. We also try to avoid aminoglycosides because they can cause ototoxicity, even when given intraperitoneally [22]. (See 'Monitoring drug levels' above.)
If the Gram stain reveals yeast or other fungus, antifungal agents should be started and the patient should be prepared for possible catheter removal depending on the final culture results; fungal infection is an indication for prompt catheter removal [20]. (See "Fungal peritonitis in peritoneal dialysis".)
Overall, our antibiotic approach is in agreement with the 2022 International Society for Peritoneal Dialysis (ISPD) guidelines [22].
Subsequent therapy — Results of peritoneal fluid cultures and antimicrobial susceptibility testing should be used to tailor the antibiotic regimen, if appropriate. In many cases, the broad-spectrum empiric regimen can be replaced by a more narrow-spectrum agent [22].
We also provide antifungal prophylaxis to all patients with confirmed peritonitis, as described above. (See 'Role of antifungal prophylaxis' above.)
Single bacterial organism — The antimicrobial regimen should be narrowed after a specific susceptible organism is identified [22] and may be further adjusted based on clinical response [20-22,36,41-43]. Although most pathogens can be effectively treated with a single agent, we treat some organisms with dual antibiotic therapy. Antibiotic administration is detailed elsewhere in this topic review, and intraperitoneal dosing is outlined in the tables (table 1 and table 2). (See 'Route of administration' above.)
●Antibiotic regimen(s) for gram-positive infections – For gram-positive infections, we favor the antibiotic with the narrowest spectrum.
•Coagulase-negative staphylococci – Infections due to these organisms often require intraperitoneal vancomycin. The exception is methicillin-susceptible isolates, which can typically be treated with intraperitoneal cefazolin (algorithm 2 and table 1 and table 2). We treat initial infections for at least 14 days; for patients with recurrent infection, we treat for at least 21 days. If the catheter is removed, we ensure at least 14 days of systemic antibiotics are received after catheter removal.
•S. aureus – Patients with cultures demonstrating methicillin-resistant S. aureus warrant treatment with vancomycin; patients with methicillin-sensitive S. aureus should be treated with a first-generation cephalosporin, such as cefazolin (algorithm 2 and table 1 and table 2).
We typically add oral rifampin for the first five to seven days of therapy for patients with S. aureus peritonitis, because some data suggest that rifampin may decrease recurrences and the drug is known to penetrate biofilms, as discussed separately [36] (see "Prosthetic joint infection: Treatment", section on 'Use of adjunctive rifampin'). However, the addition of rifampin is not a universal practice, and some reserve its use for patients with inadequate response to initial therapy. (See "Prosthetic joint infection: Treatment", section on 'Use of adjunctive rifampin'.)
We treat for at least 21 days, and, for patients whose catheter is removed due to infection, we ensure at least 14 days of systemic antibiotics are administered from the date of catheter removal. Patients who also have S. aureus bacteremia require prolonged intravenous therapy, as discussed separately. (See "Clinical approach to Staphylococcus aureus bacteremia in adults".)
•Streptococcus species – Intraperitoneal cefazolin is appropriate for infections caused by these organisms. Streptococcal isolates that are not tested for susceptibility can generally be assumed to be susceptible to penicillins and cephalosporins (algorithm 3 and table 1 and table 2).
We treat for at least 14 days, and, for patients whose catheter is removed due to infection, we ensure that 14 days of systemic antibiotics are administered from the date of catheter removal.
•Enterococcus species – We typically treat ampicillin-susceptible enterococci with intraperitoneal vancomycin; some experts recommend oral amoxicillin for these patients, but we favor intraperitoneal antibiotics over oral options because intraperitoneal antibiotics achieve reliably high concentrations in peritoneal fluid (see 'Intraperitoneal administration (preferred)' above). We favor vancomycin over ampicillin because some in vitro data suggest that the activity of ampicillin against enterococci may be limited in peritoneal fluid (algorithm 4 and table 1 and table 2) [44].
Infection with vancomycin-resistant Enterococcus (VRE) is often treated with intraperitoneal daptomycin or oral linezolid. We generally favor intraperitoneal daptomycin over oral linezolid because of toxicity-related issues and our general preference for intraperitoneal antibiotics over oral options. We suggest consultation with an infectious disease specialist for VRE peritonitis.
We treat for at least 21 days, and, for patients whose catheter is removed due to infection, we ensure at least 14 days of systemic antibiotics are administered from the date of catheter removal.
•Corynebacterium species – Infections due to these organisms typically require intraperitoneal vancomycin for a total of 14 days (table 1 and table 2).
●Antibiotic regimens for gram-negative infections – Gram-negative pathogens can be difficult to treat and may require antibiotics associated with significant toxicity or other side effects. In general, we try to avoid fluoroquinolones and aminoglycosides for the reasons described above. (See 'Alternative regimens' above.)
•Pseudomonas species – Because Pseudomonas peritonitis has a low cure rate [45,46], we treat Pseudomonas infections with two antibiotics with different mechanisms of action, such as intraperitoneal ceftazidime or cefepime plus either oral ciprofloxacin or intraperitoneal aminoglycoside (eg, gentamicin). Details regarding treatment of pseudomonal infections are found elsewhere. (See "Principles of antimicrobial therapy of Pseudomonas aeruginosa infections".)
We treat pseudomonal infections for at least 21 days, and, for patients whose catheter is removed due to infection, we ensure at least 14 days of systemic antibiotics are administered from the date of catheter removal.
•Acinetobacter species – Drug-resistant Acinetobacter peritonitis is an increasing problem worldwide, and often has a low cure rate [47]. We typically treat Acinetobacter infections with a single agent, based on susceptibility results. For patients with severe illness, we use combination therapy. Details regarding antibiotic selection for Acinetobacter infections can be found elsewhere. (See "Acinetobacter infection: Treatment and prevention".)
We treat Acinetobacter infections for at least 21 days, and, for patients whose catheter is removed due to infection, we ensure at least 14 days of systemic antibiotics are administered from the date of catheter removal.
•Stenotrophomonas maltophilia – Peritonitis due to S. maltophilia, a difficult-to-treat organism, is uncommon [48,49]. Based on results of susceptibility testing, we treat S. maltophilia infections with dual antibiotic therapy using oral trimethoprim-sulfamethoxazole plus an additional intraperitoneal antibiotic.
Details regarding antibiotic selection for Stenotrophomonas infections can be found elsewhere. (See "Stenotrophomonas maltophilia", section on 'Suggested antibiotic regimens'.)
We treat Stenotrophomonas infections for at least 21 days, and, for patients whose catheter is removed due to infection, we ensure at least 14 days of systemic antibiotics are administered from the date of catheter removal.
•E. coli and other enteric gram-negative bacilli – The enteric gram-negative bacilli are becoming increasingly resistant to common antibiotics.
In most cases, antibiotic selection should be based on susceptibility results (table 1 and table 2). Most enteric gram-negative bacilli can be treated with a single agent with the narrowest spectrum that covers the isolate (eg, intraperitoneal ceftazidime, ceftriaxone, or cefepime; oral or intraperitoneal ciprofloxacin; intraperitoneal aminoglycoside). However, the organisms bulleted below require more nuanced management:
-ESBL-producing isolates – Intraperitoneal carbapenems (eg, meropenem), oral or intraperitoneal fluoroquinolones (eg, ciprofloxacin), and intraperitoneal aminoglycosides often remain options for these organisms. Details regarding antibiotic select for ESBL infections are found elsewhere. (See "Extended-spectrum beta-lactamases", section on 'Treatment options'.)
-Enterobacter cloacae complex, Klebsiella aerogenes (formerly Enterobacter aerogenes), Citrobacter freundii – AmpC is a resistance mechanism that is harbored by some gram-negative bacilli that often cannot be detected on standard susceptibility testing. The three listed bacteria are the most common AmpC producers. As such, many experts suggest that these bacteria be presumed to be resistant to all beta-lactam agents except for cefepime and carbapenems.
For these bacteria, intraperitoneal cefepime, intraperitoneal carbapenems (eg, meropenem), oral or intraperitoneal fluoroquinolones (eg, ciprofloxacin), or intraperitoneal aminoglycosides (eg, gentamicin) can be used if reported as susceptible. All other beta-lactams (eg, ceftazidime, ceftriaxone) are typically ineffective against these organisms even if they are reported as susceptible.
Other enteric gram-negative bacilli are often mentioned as possible AmpC producers, but the prevalence of AmpC production in these bacteria is significantly lower than the three bacteria listed above. More information on AmpC producing bacteria is available elsewhere. (See "Gram-negative bacillary bacteremia in adults", section on 'Regimen choice'.)
-Carbapenem-resistant Enterobacterales (CRE) – These are among the most difficult-to-treat organisms, and infectious diseases consultation is suggested. In some cases, oral or intraperitoneal fluoroquinolones (eg, ciprofloxacin) or intraperitoneal aminoglycosides (eg, gentamicin) may be viable options. Details regarding antibiotic selection for CRE infections are found elsewhere. (See "Carbapenem-resistant E. coli, K. pneumoniae, and other Enterobacterales (CRE)", section on 'Approach to treatment'.)
We have a low threshold to remove the catheter in patients with confirmed peritonitis due to CRE (see 'Indications for catheter removal' below). Catheter removal eliminates the catheter as a nidus of ongoing bacterial replication, thereby reducing the likelihood that resistance will develop while on therapy. Because so few antibiotic options are available for CRE, the consequences of development of resistance while on therapy are much higher. Once standard antibiotic options are exhausted, more toxic agents or newer intravenous extended-spectrum antibiotics become necessary.
We treat enteric gram-negative infections for at least 21 days, and, for patients whose catheter is removed due to infection, we ensure at least 14 days of systemic antibiotics are administered from the date of catheter removal.
Polymicrobial peritonitis — Polymicrobial infection (either multiple gram-negative organisms or both gram-positive and gram-negative organisms) has been reported in 1 to 4 percent of cases of peritoneal dialysis-associated peritonitis [3,4].
●Evaluation for source – Peritonitis due to multiple enteric organisms or mixed gram-negative/gram-positive organisms should raise concern for a concurrent intra-abdominal condition such as ischemic bowel or diverticular disease. In such cases, imaging studies and surgical consultation should be obtained [20,21,50]. (See "Clinical manifestations and diagnosis of peritonitis in peritoneal dialysis", section on 'When to suspect secondary peritonitis'.)
●Antibiotic management – Broad-spectrum antimicrobial therapy should include coverage for anaerobes and the types of organisms seen on Gram stain. For patients who have gram-positive and gram-negative organisms on Gram stain, we generally treat with intraperitoneal vancomycin, intraperitoneal ceftazidime, and oral or intravenous metronidazole. For patients with mixed gram-negative organisms without gram-positive organisms, intraperitoneal vancomycin can usually be omitted from the regimen. Options for gram-negative coverage other than ceftazidime include intraperitoneal cefepime, intraperitoneal aminoglycoside (eg, gentamicin), intraperitoneal carbapenem (eg, meropenem), intraperitoneal aztreonam, or oral or intraperitoneal fluoroquinolones (eg, ciprofloxacin).
Once the organisms are identified, antibiotic coverage should be narrowed to target the pathogens (we switch to a nonaminoglycoside agent to prevent ototoxicity, if possible). If an intra-abdominal process is suspected, we typically continue anaerobic coverage for the full course of therapy even if anaerobic bacteria did not grow on culture. We treat polymicrobial infections for at least 21 days, and, for patients whose catheter is removed due to infection, we ensure at least 14 days of systemic antibiotics are administered from the date of catheter removal.
●Catheter management – Catheter removal is typically necessary for polymicrobial infections, as discussed below. (See 'Indications for catheter removal' below.)
Culture-negative peritonitis — Culture-negative peritonitis is treated with empiric antibiotics and usually has a clinical course that is similar to that of coagulase-negative Staphylococcus infection [5,51,52]. (See 'Selection of empiric antibiotics' above and 'Microbiology' above.)
For patients with culture-negative peritonitis after three days of broad spectrum empiric antimicrobial therapy, we assess clinical status and repeat the peritoneal fluid cell count, Gram stain, and culture. Our approach depends on clinical improvement, as determined by an improvement in signs/symptoms and a decrease in cell count (algorithm 5):
●Patients with clinical improvement – For patients with clinical improvement after three days of antibiotics, we stop empiric antibiotic coverage of gram-negative organisms. Provided cultures continue to show no growth, we continue empiric gram-positive coverage (eg, vancomycin) for a total of two weeks (see 'Selection of empiric antibiotics' above). Many cases of culture-negative peritonitis that improve with empiric therapy are likely caused by gram-positive organisms (eg, coagulase-negative staphylococci).
●Patients without clinical improvement – For patients without clinical improvement after three days of antimicrobial therapy, we perform specific cultures for Mycobacteria, fungal organisms, and Nocardia. Additional management depends on whether the empiric antibiotic regimen includes vancomycin:
•For patients not treated with vancomycin, we switch empiric gram-positive antibiotic coverage to vancomycin and continue existing empiric gram-negative antibiotic coverage.
•For patients treated with vancomycin, we continue broad spectrum empiric antibiotics. We also address potential (and uncommon) noninfectious causes of peritonitis by discontinuing exchanges that contain icodextrin and by reviewing all medications to look for potential allergens. In addition to adverse reactions to icodextrin, noninfectious causes of peritonitis include allergic reactions [53-61]. Icodextrin dialysate-associated peritonitis occurs either immediately or after several months of exposure [58,60,62,63]. (See "Peritoneal dialysis solutions", section on 'Glucose polymer-containing solutions (icodextrin)'.)
After five days total of antimicrobial therapy (ie, day 6 of antibiotics), we obtain peritoneal fluid for another cell count. In patients without improvement in signs/symptoms or without a decrease in cell count, the catheter should be removed and broad spectrum systemic antibiotics should be continued for at least 14 more days (see 'Indications for catheter removal' below). In patients with an improvement in signs/symptoms and a decrease in cell count, our approach is as follows:
•For patients whose empiric antibiotic regimen was changed to include vancomycin after initial empiric therapy without vancomycin, we continue broad spectrum empiric antibiotics for a 14-day course.
•For patients whose initial empiric antibiotic regimen included vancomycin, our approach depends on whether the patient has suspected noninfectious peritonitis (ie, negative cultures in the setting of recent addition of icodextrin exchanges and/or identification of a potential allergen):
-For patients without suspected noninfectious peritonitis, we continue broad spectrum empiric antibiotics for a 14-day course.
-For patients with suspected noninfectious peritonitis, we stop antibiotics and continue to observe. In patients with ongoing symptomatic improvement off antibiotics, we obtain a peritoneal fluid cell count in two weeks to ensure resolution of peritoneal fluid leukocytosis. If patients develop worsening signs/symptoms, we obtain a peritoneal fluid cell count and repeat culture and we resume broad spectrum empiric antibiotics. In such patients, restarting antibiotics should be accompanied by rapid improvement in symptoms and reduction in cell count, in which case we continue the resumed course of antimicrobial therapy for a total of 14 days; otherwise, the peritoneal dialysis catheter should be removed and systemic antibiotics continued for at least an additional 14 days.
If a specific organism is identified on culture, the choice and duration of antimicrobial therapy should be adjusted accordingly.
Fungal peritonitis — Fungal infection is an indication for immediate catheter removal. (See 'Indications for catheter removal' below.)
Details regarding management of patients with fungal peritonitis are found elsewhere. (See "Fungal peritonitis in peritoneal dialysis".)
Duration of therapy — In general, antibiotics are continued for at least 21 days for patients with S. aureus or enterococcal peritonitis and in all cases of peritonitis due to gram-negative bacilli or polymicrobial infection. Other common skin flora (eg, coagulase-negative staphylococci, Corynebacterium spp) typically respond well to 14 days. If the catheter is removed for infection, we ensure that at least 14 days of systemic therapy are provided after catheter removal.
Pathogen-specific durations are discussed above. (See 'Subsequent therapy' above.)
MONITORING CLINICAL RESPONSE — We monitor the patient's clinical response daily to make sure symptoms are stable or starting to improve. Clinical improvement should be observed within 48 hours of initiating therapy [21]. (See "Clinical manifestations and diagnosis of peritonitis in peritoneal dialysis", section on 'Evaluation'.)
By 48 hours, the fluid should be less cloudy. We repeat cell counts to assess response to therapy [21]. The cell count should be decreasing from baseline obtained on presentation. Methods for obtaining peritoneal fluid and evaluation of cell counts are described elsewhere. (See "Clinical manifestations and diagnosis of peritonitis in peritoneal dialysis", section on 'Peritoneal fluid analysis'.)
The absence of substantial improvement in the cell count suggests lack of response to treatment. In a study of 565 consecutive episodes of peritonitis, a persistent dialysate cell count >1000 by the third day of peritonitis was associated with a 64 percent likelihood of treatment failure [64]. In a subsequent study of 644 episodes of peritonitis, patients with eventual treatment failure had a 59 percent reduction in cell count after five days of antibiotics, whereas patients with successful treatment had a ≥89 percent reduction in cell count after five days of antibiotics [65]. Trends in effluent cell counts differ by causative organisms as well as host response [66].
If the patient's clinical status and/or cell count does not appear to be improving by 48 hours and cultures demonstrate a susceptible organism, we take the following steps:
●We switch from intermittent to continuous dosing of intraperitoneal antibiotics [67]. (See 'Route of administration' above.)
●For gram-negative infections, we add a second antibiotic based on sensitivities [68,69]. However, there are no good studies that support this practice, and some clinicians prefer to continue with single antibiotic rather than risk the potential toxicity associated with an additional agent.
If a cloudy effluent persists after five days of appropriate antibiotic therapy, we remove the catheter [21]. (See 'Indications for catheter removal' below.)
INDICATIONS FOR CATHETER REMOVAL — In some cases, catheter removal is required to eradicate infection. We remove the catheter in the following circumstances [20,21]:
●Refractory peritonitis, defined as peritonitis without clinical response to appropriate antibiotics within five days. A clinical response consists of improvement in signs/symptoms and a marked reduction in peritoneal fluid cell count. (See 'Monitoring clinical response' above.)
●Relapsing peritonitis, defined as a repeat episode of peritonitis within four weeks of completion of an antibiotic course. The repeat episode is caused by the same organism that caused the initial episode or follows an episode of culture-negative peritonitis. We may also remove the catheter if the patient develops a repeat episode of peritonitis with the same species within two months of completion of an antibiotic course. (See 'Culture-negative peritonitis' above.)
●Peritonitis caused by fungal organisms. (See "Fungal peritonitis in peritoneal dialysis".)
●Peritonitis caused by Mycobacteria, Nocardia, or carbapenem-resistant Enterobacterales (CRE). For peritonitis due to Mycobacterium tuberculosis, though not nontuberculous Mycobacteria, some experts attempt treatment without catheter removal [22]. However, given the high rate of mortality incurred in patients with tuberculous peritonitis [70], we remove the catheter in tuberculous and nontuberculous Mycobacteria-associated peritonitis. The management of infections due to CRE is discussed above (see 'Single bacterial organism' above). The management of Mycobacteria and Nocardia is discussed elsewhere. (See "Abdominal tuberculosis" and "Overview of nontuberculous mycobacterial infections" and "Treatment of nocardiosis".)
●Peritonitis occurring in association with intra-abdominal pathology, such as an abscess, perforation, or infarcted bowel.
●Culture-negative peritonitis with persistent symptoms and high peritoneal white blood cell count. (See 'Culture-negative peritonitis' above.)
The duration of systemic antibiotic therapy after catheter removal is typically at least 14 days, as discussed above. (See 'Duration of therapy' above.)
Simultaneous catheter removal and a new catheter replacement are acceptable for relapsing peritonitis if the dialysate can be cleared first [20,71,72]. Simultaneous catheter replacement is not possible for refractory peritonitis, fungal peritonitis, or peritonitis associated with intra-abdominal pathology. In these settings, there should be a minimum period of three to four weeks between the time of catheter removal and new catheter placement.
Early catheter removal in patients with refractory peritonitis reduces mortality and avoids prolonged episodes of peritonitis that could damage the peritoneal membrane [45,73]. In a report describing 636 episodes of peritonitis and 16 deaths, the catheter was removed between the 5th and the 10th day in six patients who died and after 10 days in seven patients who died [73].
Limited data exist concerning success with peritoneal dialysis catheter reinsertion because of catheter removal for severe peritonitis [74]. Reported success rates range from 30 to 55 percent at follow-up of 20 to 24 months, with overall mortality of 19 to 36 percent [75,76]. Technique failure was most common in those with increased dialysis vintage.
DIALYSIS PRESCRIPTION — Because of changes in peritoneal membrane characteristics during infection, adjustments to the peritoneal dialysis prescription may be necessary. Changes sometimes made to the dialysis regimen in the setting of peritonitis are discussed below.
●Rapid exchanges – If the patient is having significant pain, we perform one to two rapid in-and-out exchanges prior to the administration of antibiotics. Rapid exchanges reduce pain and may reduce the inflammatory burden and endotoxin load but have little effect on the duration of peritonitis or likelihood of cure [77,78]. If rapid exchanges are performed, dialysate containing 1.5 percent dextrose should be used so that ultrafiltration is not excessive.
●Addition of heparin to dialysate – Heparin (500 to 1000 units/L of dialysate) may be added when fibrin strands are observed in dialysate or when there is a history of clogging of the catheter. Heparin helps to lyse and/or prevent fibrin clots [78]. Heparin is otherwise not added even if dialysate is cloudy (as it almost always is in setting of peritonitis).
●Adjustment for volume overload – Patients commonly become volume overloaded during episodes of peritonitis because there is decreased ultrafiltration. Decreased ultrafiltration is due to an increase in the solute transport rate that results in rapid equilibration of fluid and solute across the inflamed peritoneal membrane and the reabsorption of fluid from the peritoneal cavity into the blood. (See "Management of hypervolemia in patients on peritoneal dialysis", section on 'Related to dialysis'.)
If this occurs, we adjust the dialysis prescription to treat volume overload. We use hypertonic (4.25 percent) dextrose solutions or icodextrin for one or two exchanges per day. We may also reduce the dwell time. Reducing the dwell time removes the fluid from the peritoneum before it can be reabsorbed. (See "Management of hypervolemia in patients on peritoneal dialysis", section on 'Icodextrin dialysate' and "Management of hypervolemia in patients on peritoneal dialysis", section on 'Additional exchange'.)
In the absence of hypervolemia, we generally do not change the dwell time or number of exchanges. Theoretically, long dwell times (four to six hours) may be preferred to short dwell times in patients with peritonitis because they are associated with higher numbers of functional intraperitoneal macrophages and immunoglobulin G concentrations [2,79]. However, there are no conclusive data that this improves outcomes, and, as noted, long dwells may result in decreased ultrafiltration.
●Cessation of dialysis – In general, we do not stop peritoneal dialysis in the setting of peritonitis. Early studies suggested that stopping peritoneal dialysis for 48 hours after giving one dose of antibiotics resulted in a high cure rate [80,81]. However, this approach is not favored for multiple reasons. Such patients would require hemodialysis, which is associated with additional risks associated with vascular catheter placement and the hemodialysis procedure. In addition, withholding peritoneal dialysis in patients with severe peritonitis may increase the risk of encapsulating peritoneal sclerosis [82]. (See "Encapsulating peritoneal sclerosis in patients on peritoneal dialysis", section on 'Risk factors'.)
However, stopping peritoneal dialysis may be necessary in severe cases of peritonitis in which the catheter is removed. (See 'Indications for catheter removal' above.)
PROGNOSIS — Peritonitis may lead to death, catheter removal, or switching dialysis modality. These risks are detailed below.
●Mortality – The reported peritonitis-associated mortality is 2 to 6 percent [2,5,51,52,83]. The mortality risk is highest with fungal pathogens, gram-negative organisms, and S. aureus [51,83]. In one retrospective Spanish study of 565 patients (693 episodes of peritonitis), mortality rates of 28, 19, and 15 percent were associated with fungus, enteric organisms, and S. aureus, respectively [83].
Peritonitis is also associated with increased mortality from noninfectious causes. In a study of 1316 peritoneal dialysis patients who died while being treated with peritoneal dialysis or within 30 days of transfer to hemodialysis, there was a much greater risk of having had peritonitis within the four months prior to death compared with the rest of the year, even though the immediate cause of death was not attributed to peritonitis in the majority of cases [84]. In particular, there was a marked increase in the risk of having had peritonitis in the 30 days prior to death among patients who died of cardiovascular, cerebrovascular, or peripheral vascular disease (odds ratio 3.4, 95% CI 2.4-4.6). Similar findings were reported in a study of 1321 peritoneal dialysis patients, which found that peritonitis was independently associated with increased risks of all-cause, cardiovascular, and infection-related mortality in patients dialyzed for longer than two years [85].
Secondary peritonitis is associated with a worse prognosis [50,86,87]. In one report, 11 of 26 patients with secondary peritonitis died [86] compared with an overall peritonitis-associated mortality of approximately 2 to 3 percent among all peritoneal dialysis patients with peritonitis [52]. In the study of secondary peritonitis, mortality correlated with the specific causes of peritonitis (particularly infarcted bowel), the time to diagnosis, and definitive surgical intervention. (See "Unique aspects of gastrointestinal disease in patients on dialysis".)
Peritonitis due to extended-spectrum beta-lactamase (ESBL) or carbapenemase-producing gram-negative organisms is associated with higher mortality [88]. Peritonitis due to multidrug-resistant gram-negative pathogens may occur in patients who have previously received broad-spectrum antimicrobial therapy, who have resided in a long-term care facility, or who are from a region where such organisms are endemic.
●Catheter removal – Most cases of peritoneal dialysis-associated peritonitis resolve with outpatient antibiotic treatment [89]. The risk of having to remove the catheter to eradicate infection is approximately 20 percent with variability between centers and with individual organisms [89]. Coagulase-negative staphylococci, streptococci, and culture-negative peritonitis have the lowest risk of failure without catheter removal (<20 percent); corynebacteria, enterococci, S. aureus, and non-Pseudomonas gram-negative peritonitis have a moderate risk of requiring catheter removal (20 to 40 percent); Pseudomonas has the highest risk of requiring catheter removal (>40 percent) [89-92].
The risk of requiring catheter removal increases if there is a concurrent exit-site or tunnel infection [93].
●Transfer to hemodialysis – Peritonitis results in a 5 to 20 percent risk of patients needing to switch to hemodialysis [51,89-92,94,95]. Organisms that are considered moderate or high risk for requiring catheter removal (corynebacteria, enterococci, S. aureus and non-Pseudomonas gram-negatives, fungus, and Pseudomonas) are associated with higher risk of switching to hemodialysis compared with coagulase-negative Staphylococcus, Streptococcus, and culture-negative peritonitis [89-92].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Dialysis".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Beyond the Basics topic (see "Patient education: Peritoneal dialysis (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●General principles – Peritonitis is a major complication of peritoneal dialysis and is the primary reason patients switch from peritoneal dialysis to hemodialysis. The majority of peritonitis cases are caused by bacteria; a small percentage of cases are caused by fungi, mostly Candida spp. (See 'Introduction' above and 'Microbiology' above.)
●Treatment – Treatment for peritoneal dialysis-associated peritonitis consists of prompt antimicrobial therapy (algorithm 1); in some cases, catheter removal is also warranted. Additional therapies may include the addition of heparin to dialysate and rapid exchanges to reduce symptoms.
•Initial empiric antimicrobial therapy – For most patients with peritoneal dialysis-associated peritonitis, we suggest initial combination therapy with vancomycin and ceftazidime rather than with other antibiotic regimens (table 3) (Grade 2C). The initial empiric antibiotic regimen should cover gram-positive and gram-negative organisms, should be based on local susceptibility data, and should account for any recent antimicrobial therapy or culture results. Intraperitoneal administration of antibiotics is preferred to intravenous administration unless the patient appears septic. (See 'Route of administration' above and 'Initial empiric therapy' above.)
The initial antibiotic regimen should be adjusted based on culture and sensitivity data. (See 'Subsequent therapy' above.)
•Polymicrobial peritonitis – Peritonitis due to multiple enteric organisms or mixed gram-negative/gram-positive organisms should raise concern for a concurrent intra-abdominal condition such as ischemic bowel or diverticular disease. (See 'Polymicrobial peritonitis' above.)
•Culture-negative peritonitis – Culture-negative peritonitis should be initially treated with empiric antibiotic therapy that covers both gram-positive and negative organisms. A repeat cell count and culture should be obtained after three days of empiric therapy to determine further management (algorithm 5). (See 'Culture-negative peritonitis' above.)
•Indications for catheter removal – Indications for catheter removal include the following (see 'Indications for catheter removal' above):
-Refractory peritonitis
-Relapsing peritonitis
-Peritonitis caused by fungal organisms (see "Fungal peritonitis in peritoneal dialysis")
-Peritonitis occurring in association with intra-abdominal pathology, such as an abscess, perforation, or infarcted bowel
-Culture-negative peritonitis with persistent symptoms and/or high peritoneal white blood cell count
We also remove the catheter for peritonitis due to specific bacteria that are difficult to treat and are associated with high mortality. For patients with peritoneal dialysis-associated peritonitis due to Mycobacteria or Nocardia spp, we suggest catheter removal and antimicrobial therapy rather than antimicrobial therapy alone (Grade 2C).
●Prognosis – Most episodes of peritoneal dialysis-associated peritonitis resolve with outpatient antibiotic treatment. Approximately 20 percent require catheter removal to eradicate infection. There is a reported associated mortality of 2 to 6 percent. (See 'Prognosis' above.)
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟