Infectious Complications in Children Undergoing Dialysis

Diagnosis

Peritonitis should be suspected whenever a cloudy effluent is present. Fever, abdominal pain, abdominal distention, and vomiting are other commonly seen symptoms that should raise suspicion. In these settings, culture and cell count of PD fluid should be tested. The diagnosis of peritonitis is empirically made in the setting of a PD fluid cell count of 100 white blood cells (WBCs)/mm ³ or more with at least 50% polymorphonuclear cells (PMNs). Since a cell count may show a false-negative result in the absence of an adequate dwell time, the fluid should ideally be collected after at least 2 hours of dwelling. The ideal method for culturing PD fluid is to centrifuge PD fluid (minimum 50 mL) to obtain a sediment, which is incubated on culture media. This method results in the lowest rate of culture-negative peritonitis. Alternatively, PD fluid can be injected into blood culture bottles for incubation.

Epidemiology

The International Pediatric Peritonitis Registry (IPPR), formed by a consortium of 44 dialysis centers across the globe, showed an incidence of 1.4 ± 0.8 peritonitis episodes per patient over a 38-month analysis period from October 2001 to December 2004. The North American Pediatric Renal Trials and Collaborative Studies (NAPRTCS) registry reported an annualized peritonitis rate of 0.64 episodes per patient year or 1 episode per 18.8 patient months over the 1992 to 2010 period. Data from the SCOPE (Standardizing Care to Improve Outcomes in Pediatric ESRD) collaborative in 2016 showed an annualized peritonitis rate of 0.42 episodes per patient year or 1 episode every 28.57 months.

Risk Factors

Risk factors for peritonitis include younger age, Black race, incontinence, early catheter uses after placement, exit-site suture placement, upward orientation of the catheter tunnel/exit site, presence of a gastrostomy tube (G-tube), exit-site colonization or infection with Pseudomonas species, and nasal or exit-site colonization with Staphylococcus aureus . Use of plastic rather than titanium catheter adapter is also associated with significantly higher rates of peritonitis. Analysis of SCOPE collaborative outcome data has identified touch contamination, defined as an accidental disconnection, contamination during treatment, or via defective PD equipment, as an independent risk factor for peritonitis. Although some of these risk factors are nonmodifiable, strategies are now being developed to standardize catheter care practices to obtain the best outcomes in PD with the lowest incidence of peritonitis.

Preventive Strategies

Based on data from the approximately 500 episodes of pediatric peritonitis in the IPPR, the International Society of Peritoneal Dialysis (ISPD) published updated pediatric guidelines for management of peritonitis in 2012. Similarly, the SCOPE collaborative has devised three “bundles” related to evidence-based practices for PD care in the areas of catheter insertion, PD training, and follow-up catheter care. Adherence with the follow-up bundle in SCOPE has been shown to reduce the rate of peritonitis significantly. Annualized peritonitis rates significantly decreased from 0.63 episodes per patient year to 0.42 at 36 months after initiating follow-up bundle use. However, there has been no association between compliance with the insertion and training bundles and the risk for peritonitis.

With regard to the surgical placement of PD catheters, recommendations have been made regarding the type of catheter, surgical technique, and perioperative care. Based on observational studies, ISPD guidelines recommend the use of a coiled double-cuff rather than a single-cuff Tenckhoff catheter inserted in the lateral or downward-facing position. No sutures should be used to anchor the catheter at the exit site because these represent a nidus for infection. A titanium adapter should be placed because plastic adapters were shown to have higher rates of peritonitis. Perioperative intravenous (IV) antibiotic administration at the time of insertion was associated with a decreased rate of early infection. A first-generation cephalosporin to cover skin flora is recommended because of the increased risk of antibiotic resistance with vancomycin.

In the immediate postoperative period, care is taken to avoid risk factors for infection. This includes immobilization of the exit site with a nonocclusive gauze and tape dressing. Dressings should be changed only once weekly under sterile conditions until the exit site is well healed unless the dressing becomes saturated with fluid or visibly dirty. Furthermore, only trained PD nurses should change a PD catheter dressing during this period. Finally, sponge baths should be used until the catheter site is fully healed, avoiding the exit-site area. Ideally, the catheter should not be used for at least 14 days after insertion to allow adequate healing time and reduce risk of early peritonitis.

Training recommendations focus on the need for a 1:1 ratio of PD nurse trainers to patients or family trained. Goals of training include the ability to safely perform all required PD procedures, the ability to recognize contamination and infection, and knowledge of the appropriate responses to these complications. Furthermore, guidelines emphasize the need for written materials to supplement the training process, as well as a posttraining assessment to ensure competency.

Beyond the perioperative period, a sterile technique remains critical in the avoidance of infection. As with all infection prevention strategies, handwashing is a crucial component of preventive care. An initial washing with soap and water is recommended, followed by the use of an alcohol-based gel. Daily or alternate-day dressing changes, the use of an antiseptic cleansing agent, such as chlorhexidine, and the administration of a topical antibiotic ointment, such as mupirocin or gentamicin, have been associated with fewer infections. Gentamicin may be preferable to mupirocin because of its efficacy against Pseudomonas species. When breaks in sterile technique are identified during the PD process, prophylactic antibiotics are indicated to minimize the risk of peritonitis. Prophylaxis is indicated for 1 to 3 days via the intraperitoneal (IP) route.

Future procedures represent another point of risk for infection. Therefore, ISPD guidelines recommend prophylactic antibiotics during dental procedures and genitourinary and gastrointestinal surgeries. In addition, the abdomen should be drained of PD fluid before the procedure to reduce the risk of development of peritonitis. In some procedures with high risk of bacterial translocation, withholding PD for 1 to 2 days, if possible, may be beneficial.

G-tube placement represents a significant source of concern because it is associated with higher rates of peritonitis and is frequently needed in PD patients to assist in appropriate nutrition. If possible, G-tube placement should be performed before or at the time of PD catheter placement. If a G-tube is placed after PD has been instituted, the open surgical technique is preferable over the laparoscopic approach because it enables immediate suturing of the stomach to the abdominal wall, minimizing the amount of gastric leakage. Appropriate antibiotic prophylaxis should be given, and PD should be withheld for at least 1 day. Antifungal prophylaxis is also indicated because of an observed increased risk of fungal peritonitis with G-tube placement.

Microbiology

Causative pathogens of peritonitis vary extensively by locale. Analysis from the IPPR showed that whereas Gram-positive peritonitis is more common in Europe, Pseudomonas species were eight times more common in the United States. Furthermore, in North America, culture-negative peritonitis accounted for 11% of episodes, but in Mexico, it accounted for 67%. Geographic differences are thought to be due to both environmental factors as well as differences in regional practices regarding chronic catheter care.

Currently, there seems to be a general trend toward fewer Gram-positive infections overall. This may be due to improvement in technique, as well as the implementation of S. aureus colonization eradication regimens. In 1990, a European study by Schaefer et al. showed that approximately 65% of peritonitis cases were Gram-positive, and 20% of cases were Gram-negative. IPPR data from 2007 showed that in the United States, approximately 45% of peritonitis cases were Gram-positive, and 40% were Gram-negative. SCOPE collaborative analysis from 2016, using a large sample size, showed that approximately 40% of peritonitis cases were Gram-positive, 20% were Gram-negative, and 10% were polymicrobial. The most common Gram-positive isolates from both IPPR and SCOPE collaborative data were coagulase-negative staphylococci followed by S. aureus . The most common Gram-negative isolates from both IPPR and SCOPE collaborative data were Pseudomonas species, followed by Klebsiella . Fig 86.1 , taken from a SCOPE collaborative analysis, shows the rates of different causative organisms. Fungal infections represent another important source of peritonitis, ranging from 3% to 9% of all cases, and typically have a more severe course.

Treatment

Bacterial Peritonitis

IP antibiotic administration represents the mainstay of management for peritonitis. IP administration achieves a rapid, high concentration of drug levels at the site of infection, and absorption from the peritoneal cavity generally results in therapeutic blood levels as well. Most antibiotics are administered continuously, given as a constant dose per liter injected into the dialysate, with the subsequent total amount received dependent on the patient’s dialysis prescription. Based on the pharmacokinetic profiles of various antibiotic agents, as well as the patient’s residual renal function, dosing can sometimes be done intermittently rather than continuously. In these cases, drug levels should be checked to determine a redosing schedule. Table 86.1 shows the commonly used antibiotics and their recommended dosing.

Table 86.1

Pharmacologic Agents and Dosing Regimens for Treatment of Peritonitis

From Warady BA, Bakkaloglu S, Newland J, et al. Consensus guidelines for the prevention and treatment of catheter-related infections and peritonitis in pediatric patients receiving peritoneal dialysis: 2012 update. Perit Dial Int. 2012;32(suppl):S29-S86.

Antibiotic Dosing Recommendations for the Treatment of Peritonitis
	Therapy Type
	Continuous ⁎		Intermittent ⁎
Antibiotic Type	Loading Dose	Maintenance Dose
Aminoglycosides (IP) †
Gentamicin	8 mg/L	4 mg/L	—
Netilmicin	8 mg/L	4 mg/L	Anuric: 0.6 mg/kg
Tobramycin	8 mg/L	4 mg/L	Non-anuric: 0.75 mg/kg
Amikacin	25 mg/L	12 mg/L	—
Cephalosporins (IP)
Cefazolin	500 mg/L	125 mg/L	20 mg/kg
Cefepime	500 mg/L	125 mg/L	15 mg/kg
Cefotaxime	500 mg/L	250 mg/L	30 mg/kg
Ceftazidime	500 mg/L	125 mg/L	20 mg/kg
Glycopeptides (IP) ‡
Vancomycin	1000 mg/L	25 mg/L	30 mg/kg; Repeat dosing: 15 mg/kg every 3–5 days
Teicoplanin §	400 mg/L	20 mg/L	15 mg/kg every 5–7 days
Penicillins (IP) †
Ampicillin	—	125 mg/L	—
Quinolones (IP)
Ciprofloxacin	50 mg/L	25 mg/L	—
Others
Aztreonam (IP)	1000 mg/L	250 mg/L	—
Clindamycin (IP	300 mg/L	150 mg/L	—
Imipenem-cilastin (IP)	250 mg/L	50 mg/L	—
Linezolid (PO)	Age < 5 years: 30 mg/kg/day divided into three doses Age 5–11 years: 20 mg/kg/day divided into two doses Age ≥ 12 years: 600 mg/dose twice daily		—
Metronidazole (PO)	30 mg/kg/day divided into three doses (maximum, 1.2 g/day)		—
Rifampin (PO)	10–20 mg/kg/day divided into two doses (maximum, 600 mg/day)		—
Antifungals
Fluconazole (IP, IV, or PO)	6–12 mg/kg every 24–48 h (maximum, 400 mg/day)		—
Caspofungin (IV only)	70 mg/m 2 on day 1 (maximum, 70 mg/day)	50 mg/m 2 /day (maximum, 50 mg/day)	—

⁎ For continuous therapy, the exchange with the loading dose should dwell for 3 to 6 hours; all subsequent exchanges during the treatment course should contain the maintenance dose. For intermittent therapy, the dose should be applied once daily in the long dwell unless otherwise specified.

† Aminoglycosides and penicillins should not be mixed in dialysis fluid because of the potential for inactivation.

‡ In patients with residual renal function, glycopeptide elimination may be accelerated. If intermittent therapy is used in such a setting, the second dose should be time based on a blood level obtained 2 to 4 days after the initial dose. Redosing should occur when the blood level is below 15 mg/L for vancomycin, or below 8 mg/L for teicoplanin. Intermittent therapy is not recommended for patients with residual renal function unless serum levels of the drug can be monitored in a timely manner.

§ Teicoplanin is not currently available in the United States.

Empiric treatment should begin with both Gram-positive and Gram-negative coverage and should be adjusted accordingly based on culture results. Cefepime has adequate coverage of both Gram-positive and Gram-negative organisms and is recommended as first-line treatment. Alternatively, a first-generation cephalosporin plus ceftazidime (a third-generation cephalosporin) or an aminoglycoside can be used in combination. In patients with a history of methicillin-resistant S. aureus (MRSA) or centers with high rates of MRSA (> 10% of all S. aureus infections), vancomycin should be started empirically with any regimen pending culture results. Figs. 86.2 and 86.3 show recommended treatment strategies based on culture results.

The duration of antibiotic treatment for peritonitis depends on the organism isolated and severity of the infection. For coagulase-negative staphylococci and Streptococcus species, a 2-week course of treatment is considered sufficient. S. aureus peritonitis is frequently more severe, so a 3-week course is recommended. Enterococcus species, although it usually causes a mild infection, is typically treated for 2 to 3 weeks because the initial empiric treatment often does not cover the bacteria. In settings of Gram-negative peritonitis other than Pseudomonas species, the treatment regimen is generally 2 weeks. However, in cases of Pseudomonas species or other extended-spectrum β-lactamase (ESBL)–producing species, a 3-week course is recommended. Pseudomonas species can create a biofilm within the catheter lumen, increasing the risk of treatment failure. For that reason, the addition of an aminoglycoside to the treatment regimen is recommended for synergy.