Peritonitis and Exit-Site Infection

Fig. 16.1

Purulent dialysate (Courtesy Yong-Lim Kim, Korea)

PD patients presenting with cloudy effluent is presumed to have peritonitis and treated as such until the diagnosis can be confirmed or excluded. PD effluent is tested for cell count, differential, Gram stain, and culture whenever peritonitis is suspected. Differential diagnosis of cloudy effluent includes culture-positive infectious peritonitis, infectious peritonitis with sterile cultures, chemical peritonitis, calcium channel blockers, eosinophilia of the effluent, hemoperitoneum, malignancy (rare), chylous effluent (rare), and specimen taken from “dry” abdomen.

16.2.4 Identification of Causative Organism

Blood-culture bottle is the preferred technique for bacterial culture of PD effluent. Bedside inoculation of 5–10 mL effluent in two (aerobic and anaerobic) blood-culture bottles has a reasonable sensitivity, and the culture-negative rate is typically around 10–20% (Alfa et al. 1997; Azap et al. 2006). Centrifugation of 50 mL PD effluent at 3000×g for 15 min, followed by resuspension of the sediment in 3–5 mL supernatant and inoculation on solid culture media or standard blood-culture media, increases the yield by 5–10 times but is more cumbersome (Sewell et al. 1990; Chow et al. 2007).

Specimens should arrive at the laboratory within 6 h. If immediate delivery to the laboratory is not possible, the inoculated culture bottles should ideally be incubated at 37 °C. Sampling and culture methods are reviewed and improved if more than 15% of peritonitis episodes are culture-negative.

16.2.5 Treatment

16.2.5.1 Initial Management (Fig. 16.2)

Empirical antibiotic therapy is initiated as soon as possible after appropriate microbiological specimens have been obtained. Empirical antibiotic regimens are center-specific and cover both gram-positive and gram-negative organisms. Gram-positive organisms are covered by vancomycin or a first-generation cephalosporin and gram-negative organisms by a third-generation cephalosporin or an aminoglycoside (Li et al. 2016).

Fig. 16.2

Initial management of peritonitis (reproduced from Li et al. 2016)

16.2.5.2 Dosage of Antibiotics (Tables 16.1 and 16.2)

Intraperitoneal (IP) antibiotics are the preferred route of administration unless the patient has features of systemic sepsis. IP aminoglycoside is administered as daily intermittent dosing, and prolonged courses of IP aminoglycoside are avoided. IP vancomycin is administered intermittently and the serum vancomycin level is kept above 15 μg/mL. IP cephalosporin is administered either continuously (in each exchange) or on a daily intermittent basis (Li et al. 2016).

Table 16.1

Intraperitoneal antibiotic dosing recommendations for treatment of peritonitis (reproduced from Li et al. 2016)

	Intermittent (1 exchange daily)	Continuous (all exchanges)
Aminoglycosides
Amikacin	2 mg/kg daily	LD 25 mg/L, MD 12 mg/L
Gentamicin	0.6 mg/kg daily	LD 8 mg/L, MD 4 mg/L
Netilmicin	0.6 mg/kg daily	MD 10 mg/L
Tobramycin	0.6 mg/kg daily	LD 3 mg/kg, MD 0.3 mg/kg
Cephalosporins
Cefazolin	15–20 mg/kg daily	LD 500 mg/L, MD 125 mg/L
Cefepime	1000 mg daily	D 250–500 mg/L, MD 100–125 mg/L
Cefoperazone	No data	LD 500 mg/L, MD 62.5–125 mg/L
Cefotaxime	500–1000 mg daily	No data
Ceftazidime	1000–1500 mg daily	LD 500 mg/L, MD 125 mg/L
Ceftriaxone	1000 mg daily	No data
Penicillins
Penicillin G	No data	LD 50,000 unit/L, MD 25,000 unit/L
Amoxicillin	No data	MD 150 mg/L
Ampicillin	No data	MD 125 mg/L
Ampicillin/sulbactam	2 g/1 g every 12 h	LD 750–100 mg/L, MD 100 mg/L
Piperacillin/tazobactam	No data	LD 4 g/0.5 g, MD 1 g/0.125 g
Others
Aztreonam	2 g daily	LD 1000 mg/L, MD 250 mg/L
Ciprofloxacin	No data	MD 50 mg/L
Clindamycin	No data	MD 600 mg/bag
Daptomycin	No data	LD 100 mg/L, MD 20 mg/L
Imipenem/cilastatin	500 mg in alternate exchange	LD 250 mg/L, MD 50 mg/L
Ofloxacin	No data	LD 200 mg, MD 25 mg/L
Polymyxin B	No data	MD 300,000 unit (30 mg)/bag
Quinupristin/dalfopristin	25 mg/L in alternate exchange^a	No data
Meropenem	1 g daily	No data
Teicoplanin	15 mg/kg every 5 days	LD 400 mg/bag, MD 20 mg/bag
Vancomycin	15–30 mg/kg every 5–7 days^b	LD 30 mg/kg, MD 1.5 mg/kg/bag
Antifungals
Fluconazole	IP 200 mg every 24–48 h	No data
Voriconazole	IP 2.5 mg/kg daily	No data

LD loading dose in mg, MD maintenance dose in mg, IP intraperitoneal, APD automated peritoneal

^aGiven in conjunction with 500 mg intravenous twice daily

^bSupplemental doses may be needed for APD patients

Table 16.2

Systemic antibiotic dosing recommendations for treatment of peritonitis (reproduced from Li et al. 2016)

Drug	Dosing
Antibacterials
Ciprofloxacin	Oral 250 mg BD^a
Colistin	IV 300 mg loading, then 150–200 mg daily^b
Ertapenem	IV 500 mg daily
Levofloxacin	Oral 250 mg daily
Linezolid	IV or oral 600 mg BD
Moxifloxacin	Oral 400 mg daily
Rifampicin	450 mg daily for BW <50 kg
Rifampicin	600 mg daily for BW ≥50 kg
Trimethoprim/sulfamethoxazole	Oral 160 mg/800 mg BD
Antifungals
Amphotericin	IV test dose 1 mg; starting dose
	0.1 mg/kg/day over 6 h; increased to target dose
	0.75–1.0 mg/kg/day over 4 days
Caspofungin	IV 70 mg loading, then 50 mg daily
Fluconazole	Oral 200 mg loading, then 50–100 mg daily
Flucytosine	Oral 1 g/day
Posaconazole	IV 400 mg every 12 h
Voriconazole	Oral 200 mg every 12 h

BD twice a day, IV intravenous, BW body weight

^aCiprofloxacin 500 mg BD may be needed if residual glomerular filtration rate is above 5 mL/min

^bExpressed as colistin base activity (CBA)

16.2.5.3 Subsequent Management of Peritonitis

Antibiotic therapy is adjusted to narrow-spectrum agents, as appropriate, once culture results and sensitivities are known. The management algorithms for gram-positive cocci and gram-negative bacilli identified in dialysis effluent are summarized in Figs. 16.3 and 16.4, respectively (Li et al. 2016).

Fig. 16.3

Management algorithm for gram-positive cocci identified in dialysis effluent (reproduced from Li et al. 2016)

Fig. 16.4

Management algorithm for gram-negative bacilli or mixed bacterial growth identified in dialysis effluent (reproduced from Li et al. 2016)

Refractory peritonitis is defined as failure of the effluent to clear after 5 days of appropriate antibiotics. Catheter removal is indicated in case of refractory peritonitis , or earlier if the patient’s clinical condition is deteriorating, in order to preserve the peritoneum for future PD as well as preventing morbidity and mortality. Prolonged attempts to treat refractory peritonitis by antibiotics without catheter removal are associated with extended hospital stay, peritoneal membrane damage, increased risk of fungal peritonitis, and excessive mortality (Choi et al. 2004).

Terminology of peritonitis is as follows: (1) recurrent peritonitis , an episode that occurs within 4 weeks of completion of therapy of a prior episode but with a different organism; (2) relapsing peritonitis , an episode that occurs within 4 weeks of completion of therapy of a prior episode with the same organism or one sterile episode; and (3) repeat peritonitis , an episode that occurs more than 4 weeks after completion of therapy of a prior episode with the same organism. Timely catheter removal is considered for relapsing, recurrent, or repeat peritonitis episodes. When compared to non-relapsing episodes , relapsing ones are associated with a lower rate of cure, more ultrafiltration problems, and higher rate of technique failure (Szeto et al. 2009; Lane et al. 2010). Recurrent peritonitis episodes had a worse prognosis than relapsing ones (Szeto et al. 2009; Burke et al. 2011).

Coagulase-Negative Staphylococcus

Coagulase-negative staphylococci generally are treated with IP cephalosporins or vancomycin, according to antimicrobial susceptibility, for a period of 2 weeks (Li et al. 2016). Many patients with S. epidermidis peritonitis have mild clinical symptoms and respond well to treatment as outpatients (Szeto et al. 2008; Camargo et al. 2014; Fahim et al. 2010). The patient’s exchange technique should be reviewed to prevent another episode.

Enterococcus Species

Enterococcal peritonitis is treated for 3 weeks with IP vancomycin. Adding IP aminoglycoside for severe enterococcal peritonitis is suggested. For peritonitis due to vancomycin-resistant Enterococcus (VRE), treatment for 3 weeks with IP ampicillin is suggested, if the organism is susceptible or with alternative antibiotics (linezolid, quinupristin/dalfopristin, daptomycin, or teicoplanin, based on antimicrobial susceptibilities) if the organism is ampicillin-resistant (Li et al. 2016).

Streptococcal Species

Streptococcal peritonitis is treated with appropriate antibiotics, such as IP ampicillin, for 2 weeks (Li et al. 2016). Peritonitis episodes caused by streptococci usually respond well to antibiotic treatment (Shukla et al. 2006; O’Shea et al. 2009), but viridans streptococcal peritonitis is more likely to be refractory (Chao et al. 2015). Cefazolin and vancomycin are often effective.

Staphylococcus Aureus

Staphylococcus aureus peritonitis is treated with effective antibiotics for 3 weeks (Li et al. 2016). Peritonitis episodes caused by Staphylococcus aureus are often secondary to exit-site or tunnel infection, although touch contamination is also common. If the bacterial isolate is methicillin-sensitive, a first-generation cephalosporin is the drug of choice (Szeto et al. 2007; Govindarajulu et al. 2010). If the isolate is methicillin-resistant, IP vancomycin is the drug of choice, but teicoplanin and daptomycin can be used as alternatives (Lin et al. 2011).

Corynebacterium Peritonitis

Corynebacterial peritonitis is treated with effective antibiotics for 3 weeks (Li et al. 2016). In a retrospective study, Corynebacterium peritonitis often resulted in relapse or repeat episodes, catheter removal, permanent hemodialysis transfer, and death (Barraclough et al. 2009). For patients with concomitant exit-site or catheter tunnel infection caused by Corynebacterium, early catheter removal should be considered (Li et al. 2016).

Pseudomonas Peritonitis

Pseudomonas peritonitis is treated with two antibiotics with different mechanisms of action and to which the organism is sensitive (e.g., IP gentamicin or oral ciprofloxacin with IP ceftazidime or cefepime) for 3 weeks. Pseudomonas peritonitis with concomitant exit-site and tunnel infection is treated with catheter removal (Li et al. 2016). Carbapenems, such as imipenem, meropenem, and doripenem, are valid alternatives, especially if the bacterial isolate is resistant to cephalosporin and antipseudomonal penicillins.

Other Gram-Negative Bacteria

Non-Pseudomonas gram-negative peritonitis is treated with effective antibiotics for at least 3 weeks (Li et al. 2016). SPICE organisms (Serratia, Pseudomonas, indole-positive organisms such as Proteus and Providentia, Citrobacter, and Enterobacter) have amp-C beta-lactamases, which inactivate cephalosporins, and have a high risk of relapse (Szeto et al. 2006).

Extended-spectrum beta-lactamases (ESBLs) are resistant to all cephalosporins but usually susceptible to carbapenems (Wong et al. 2007; Feng et al. 2014). Carbapenem-resistant Enterobacteriaceae (CRE)/ Klebsiella pneumoniae carbapenemase (KPC)-producing bacteria are usually resistant to all classes of beta-lactams, usually resistant to fluoroquinolones, variably susceptible to aminoglycosides , but usually susceptible to polymyxin and colistin (Wong et al. 2007; Zhang et al. 2014).

Isolation of a Stenotrophomonas species, while infrequent, requires special attention, as it is sensitive to only a few antimicrobial agents (Szeto et al. 1997; Tzanetou et al. 2004).

Polymicrobial Peritonitis

If multiple enteric organisms (multiple gram-negative or mixed gram-negative/gram-positive organisms) are grown from PD effluent, surgical evaluation is obtained immediately when there is no prompt clinical response and the patient is treated with metronidazole in conjunction with IP vancomycin and either IP aminoglycoside or IP ceftazidime for a minimum period of 3 weeks (Li et al. 2016).

If multiple gram-positive organisms are grown from PD effluent, we suggest that patients be treated with effective antibiotics for 3 weeks (Li et al. 2016).

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