Your activity: 219 p.v.
your limit has been reached. plz Donate us to allow your ip full access, Email: sshnevis@outlook.com

Non-access-related infections in chronic dialysis patients

Non-access-related infections in chronic dialysis patients
Author:
Rebecca J Schmidt, DO, FACP
Section Editor:
Steve J Schwab, MD, FACP, FASN
Deputy Editor:
Eric N Taylor, MD, MSc, FASN
Literature review current through: Dec 2022. | This topic last updated: Sep 23, 2021.

INTRODUCTION — In addition to infections associated with dialysis access devices, patients with end-stage kidney disease (ESKD) who require renal replacement therapy may be susceptible to non-access-related infections. Diagnostic strategies for these infections are similar to those used for patients without kidney disease. However, a higher index of suspicion and a lower threshold for the initiation of a search are appropriate since patients with ESKD are frequently diabetic and/or immunosuppressed because of the retention of uremic toxins. Careful attention to appropriate dosing of antibiotics and the avoidance (if possible) of nephrotoxic drugs in the patient with residual kidney function are also significant issues.

Many of the infections reviewed in this topic are not unique to the dialysis patient. As a result, although the likelihood of their occurrence may be increased, special considerations and guidelines for the dialysis patient are not available. Diagnostic and treatment strategies must be tailored to the individual patient, including the consequences of kidney disease and other comorbid conditions, the geographic location, and specific environmental exposures.

A review of the clinical characteristics of infections not related to the dialysis access is presented here. Reviews of access-related infections and the clinical manifestations and treatment of sepsis in dialysis patients, a complication most commonly due to infection of dialysis access devices, are discussed separately. (See "Arteriovenous fistula creation for hemodialysis and its complications" and "Clinical manifestations and diagnosis of peritonitis in peritoneal dialysis" and "Arteriovenous graft creation for hemodialysis and its complications" and "Overview of complications of central venous catheters and their prevention in adults", section on 'Catheter-related infection' and "Tunneled hemodialysis catheter-related bloodstream infection (CRBSI): Management and prevention".)

EPIDEMIOLOGY — Data from the United States Renal Data System (USRDS) indicates that infections continue to be a leading cause of death among patients with end-stage kidney disease (ESKD) [1,2], accounting for approximately 10 to 13 percent of all deaths in 2018 [3-5]. The vast majority result from bacteremia/sepsis, followed by pulmonary infection [1].

Compared with the population with normal kidney function, patients with chronic kidney disease (CKD) and ESKD are at higher risk of contracting bacterial infections, particularly urinary tract infections, pneumonia, and sepsis [6-9]. They are also more likely to have an infection at the time of hospitalization [10].

Because of their propensity for causing sepsis, infections related to dialysis access devices are potentially catastrophic [11,12]. The annual mortality secondary to sepsis is 100- to 300-fold higher in dialysis patients [11] (see "Tunneled hemodialysis catheter-related bloodstream infection (CRBSI): Management and prevention" and "Overview of complications of central venous catheters and their prevention in adults", section on 'Catheter-related infection'). In addition, a prospective study evaluating the outcome of 65 episodes of Staphylococcus aureus bacteremia in hemodialysis patients (89 percent of which were due to an access) found that metastatic complications and death occurred in 44 and 14 percent of patients, respectively. In contrast, other studies suggest that non-access-related infections are less common and not as devastating, accounting for an overall mortality rate of less than 3 percent [13].

Patients on dialysis are at a higher risk for acquiring infection caused by multidrug-resistant organisms and for death resulting from infection [14]. This is because of their likelihood of requiring treatment that involves invasive devices, their frequent exposure to antibiotics, and their altered immunity [15]. As reported by the USRDS, death due to infection in patients over the age of 65 years is approximately twice that of younger patients [3]. Smoking has been shown to be an important risk factor for infection-related morbidity and mortality among hemodialysis patients [16].

Among patients undergoing chronic renal replacement therapy, the most important infections not related to the dialysis access include the following:

Infections of the upper and lower respiratory tract

Human immunodeficiency virus (HIV) infection

Infections of the central nervous system, including mucormycosis

Gastrointestinal infections, such as hepatitis and Clostridioides difficile colitis

Genitourinary tract infections, including pyocystis

Cellulitis and osteomyelitis

Infections due to highly drug-resistant organisms

Tuberculosis

RESPIRATORY SYSTEM — Respiratory tract infections in dialysis patients may be community or hospital acquired. As previously mentioned, respiratory infections are the second leading cause of infection-related deaths.

Upper respiratory tract — Compared with the general population, patients with end-stage kidney disease (ESKD) are not overly susceptible to sinusitis, rhinitis, or pharyngitis. Diagnoses and treatments are therefore similar to those for the general population. However, special attention must be given to accurate drug dosing and the loss of antibiotics across the dialysis membrane among those undergoing hemodialysis. (See "Chronic rhinosinusitis: Management" and "An overview of rhinitis" and "Acute sinusitis and rhinosinusitis in adults: Clinical manifestations and diagnosis".)

Lower respiratory tract — Bronchitis and pneumonia are common in dialysis patients. In one retrospective study of dialysis patients, the probability of being hospitalized from pneumonia was 9 and 36 percent at one and five years, respectively [17]. A subsequent observational study found a pneumonia incidence rate of 21.4 events/100 patient-years, with 90.1 percent requiring hospitalization, and a 30-day fatality of 10.7 percent in Medicare patients on dialysis [18]. Significantly higher hospitalizations also occurred in the 12 months following the pneumonia episode, increasing the overall costs [18].

Pneumonia is an important cause of death and hospitalization in patients, carrying significant risk for those with advanced chronic kidney disease (CKD) [19]. Compared with the population with normal kidney function, the rate of pneumonia is three times greater in those with CKD and five times greater in those with ESKD [6]. One-in-five ESKD patients developed pneumonia during their first year on dialysis, and 42 percent of these required hospitalization [20]. The lengths of hospitalization in CKD and ESKD patients with pneumonia are similar and are four to six times longer than the non-CKD population [6].

A retrospective study of the bacteriology and outcomes of empyema in 84 stage 4 CKD and 40 ESKD patients found that most empyemas were secondary to pneumonia. Gram-negative organisms were cultured in 67 percent of stage 4 CKD patients (34 percent were Klebsiella pneumoniae), but aerobic gram-positive organisms predominated in the ESKD patients (54 percent, with 67 percent of those S. aureus) [21]. Compared with the stage 4 CKD patients, ESKD patients had a higher catheter-associated infection rate and lower infection-associated mortality [21].

Compared with patients without kidney disease, bronchitis and pneumonia may be more difficult to diagnose since pulmonary fluid fluctuates markedly with dialysis treatments. Nevertheless, the presence of a productive cough, fever, chills, pleuritic pain, and/or dyspnea suggest an infectious pulmonary process. The diagnosis may be confirmed by sputum evaluation and chest radiograph. Treatment should not be withheld if a high index of suspicion remains, despite the absence of diagnostic test results. (See "Clinical evaluation and diagnostic testing for community-acquired pneumonia in adults" and "Community-acquired pneumonia in adults: Assessing severity and determining the appropriate site of care" and "Treatment of community-acquired pneumonia in adults in the outpatient setting".)

HUMAN IMMUNODEFICIENCY VIRUS INFECTION — In early studies, survival on dialysis was short in most patients with acquired immune deficiency syndrome (AIDS; only a few months), although some asymptomatic patients or those with early AIDS survived for one to two years. Subsequent studies, however, have noted prolonged survival in infected patients requiring renal replacement therapy. This is discussed in detail separately. (See "Human immunodeficiency virus and dialysis".)

NERVOUS SYSTEM — Meningitis and infections of the brain parenchyma should be considered in dialysis patients with fever and/or central nervous system symptoms or findings.

Meningitis — A paucity of literature exists concerning the incidence of meningitis in dialysis patients. Streptococcus meningitis, an uncommon infection in all adults, was reported as a complication of peritonitis in one peritoneal dialysis patient [22].

Fungal meningitis has also been reported in patients with end-stage kidney disease (ESKD). Cryptococcal meningoencephalitis, the most frequent manifestation of cryptococcal infection, has been noted with increased frequency among the general patient population because of human immunodeficiency virus (HIV) infection. Involvement of the meninges with Cryptococcus in peritoneal dialysis patients most commonly results from systemic disease initially arising from infection of the peritoneum [23-25]. (See "Clinical manifestations and diagnosis of Cryptococcus neoformans meningoencephalitis in patients without HIV".)

Herpes zoster — Varicella-zoster virus (VZV) infection causes two clinically distinct forms of disease: varicella (chickenpox) and herpes zoster (shingles) (see "Epidemiology, clinical manifestations, and diagnosis of herpes zoster", section on 'Risk factors').

Chronic kidney disease (CKD) is a risk factor for the development of herpes zoster [26-28]. In one study, compared with patients without ESKD, patients with ESKD on hemodialysis had twice the risk of zoster by 4.7 years of follow-up (adjusted hazard ratio 1.98, 95% CI 1.72-2.27) [27]. Vaccination against herpes zoster for ESKD patients is discussed at length elsewhere [29]. (See "Immunizations in patients with end-stage kidney disease", section on 'Varicella-zoster virus vaccine'.)

Treatment with antiviral agents such as valacyclovir requires adjustment in dose for dialysis patients.

Mucormycosis — Mucormycosis, a life-threatening fungal disease, is characterized by fungal sinusitis with invasion of adjacent structures, including the brain. It most commonly occurs in immunocompromised and diabetic patients and dialysis patients treated with deferoxamine. The fungal infection may be contracted from the environment and then disseminate, frequently affecting the central nervous system and sinuses (rhinocerebral mucor). (See "Fungal rhinosinusitis".)

Hemodialysis patients in whom aluminum chelation therapy with deferoxamine has been administered at relatively high doses appear to be at significant risk for mucormycosis. Presenting forms of the infection most commonly include rhinocerebral and disseminated disease (31 and 44 percent, respectively). (See "Aluminum toxicity in chronic kidney disease".)

Mucormycosis infecting the peritoneum has also been reported in peritoneal dialysis patients. In one case report, Rhizopus species grew from cultures obtained from a patient with clinical signs of peritonitis [30]. The patient had no known risk factor for the infection.

The management of these fungal infections is discussed in the appropriate topic reviews.

GASTROINTESTINAL SYSTEM

Gallbladder and biliary disease — A paucity of literature exists concerning the prevalence of cholecystitis and cholecystolithiasis in patients with end-stage kidney disease (ESKD). In an observational study of 179 patients with ESKD who presented to the emergency department with abdominal pain, approximately 6 percent were diagnosed with cholecystitis or biliary colic [31].

The prevalence of cholecystolithiasis in patients with ESKD may be comparable to that in the general population. In one ultrasonographic study, no significant difference was observed in the prevalence of cholecystolithiasis in 73 hemodialysis patients and a control group (16 and 23 percent, respectively) [32]. A case report of emphysematous cholecystitis in a peritoneal dialysis patient suggests that ischemia may play a role in the development of this entity [33].

Common bile duct dilatation may occur more commonly among patients with kidney disease due to polycystic kidney disease compared with those without the disorder. In one study, for example, 22 of 55 patients (40 percent) with polycystic kidney disease and varying levels of kidney function were found to have biliary dilatation measuring at least 7 millimeters compared with 5 of 55 controls (9.1 percent) matched for age, sex, kidney function, and duration of dialysis [34]. Whether this is associated with an enhanced risk of biliary infection and/or pathology is unknown.

The clinical presentation and overall management of dialysis patients with cholecystitis are similar to those without kidney disease. (See "Acute calculous cholecystitis: Clinical features and diagnosis" and "Treatment of acute calculous cholecystitis".)

Visceral leakage causing peritonitis — Peritonitis is a common complication in patients undergoing peritoneal dialysis. Although associated with significant morbidity, it is usually easily treatable (see "Microbiology and therapy of peritonitis in peritoneal dialysis"). However, peritonitis resulting from enteric bacteria is frequently caused by injury to gastrointestinal viscera and may have devastating consequences. Peritonitis acquired by virtue of microscopic perforation may be insidious, with subtle or no radiographic abnormalities despite evolving clinical symptoms. In a review of 230 peritoneal dialysis patients followed over eight years, approximately 30 percent of peritonitis episodes resulting from enteric organisms were due to documented visceral leakage, including cholecystitis, ischemic bowel disease, viscus perforation, or diverticulitis [35]. Among these 26 patients with visceral disease, 50 percent died, and 30 percent switched to hemodialysis.

Helicobacter pylori infection — The literature is limited with regard to the prevalence of gastroduodenal Helicobacter pylori infection in dialysis patients. In a study of over 1200 patients with ESKD who underwent an upper endoscopy for transplant evaluation, H. pylori was detected in approximately one-third of the patients [36]. The prevalence, diagnosis, and management of H. pylori infection in dialysis patients are discussed separately. (See "Unique aspects of gastrointestinal disease in dialysis patients".)

Hepatitis — Infectious hepatitis, particularly with hepatitis B and C, is a significant cause of morbidity and mortality in hemodialysis patients, with hepatitis C being a leading cause of liver disease. Fortunately, the incidence of both hepatitis B and C infections is declining in this patient population.

Discussions concerning the epidemiology, diagnosis, and treatment of hepatitis B and C infections in patients with and without kidney disease are presented separately. (See "Hepatitis C virus infection in patients on maintenance dialysis" and "Hepatitis B virus and dialysis patients".)

Gastroenteritis — Patients with ESKD are susceptible to the same viral gastroenteritides as the general population, although their ability to combat such illnesses may be suppressed. An important issue in the dialysis patient with significant gastrointestinal fluid loss (by vomiting and/or diarrhea) is the accurate assessment of intravascular volume to avoid a substantial decrease in the effective circulating volume with dialysis therapy. Careful attention must therefore be given to variations in blood pressure during the procedure and the accurate determination of dry weight. Acute symptomatic relief may be obtained with the administration of an antidiarrheal agent, such as loperamide given at a dose of 2 to 4 mg by mouth (PO) initially then 2 mg after each unformed stool up to 10 to 12 mg daily.

Diverticulitis — Dialysis patients develop diverticulitis at least as frequently as nondialysis patients. An increased incidence is observed in patients with polycystic kidney disease since a majority of such individuals who require dialysis have diverticula. (See "Autosomal dominant polycystic kidney disease (ADPKD): Extrarenal manifestations".)

The presentation of diverticulitis in the chronically ill dialysis patient may be more insidious than that of the patient without kidney disease. The typical clinical manifestations of a patient presenting with acute diverticulitis are discussed separately. (See "Clinical manifestations and diagnosis of acute diverticulitis in adults", section on 'Clinical manifestations'.)

Management must be individualized but is essentially similar to that for patients not on dialysis (see "Acute colonic diverticulitis: Medical management"). Nonoperative management may be preferred for patients with ESKD who have acute diverticulitis. In one study of 962 patients with ESKD and matched controls >65 years of age who underwent surgical intervention for diverticulitis, those with ESKD had a higher rate of in-hospital mortality and postoperative complications compared with those without ESKD [37].

Clostridioides difficile colitis — Dialysis patients are particularly susceptible to C. difficile colitis since they are commonly administered antibiotics. In one study of 62 dialysis patients and 8 individuals with acute kidney disease, 110 episodes of C. difficile colitis reportedly occurred over a two-year period [38]. In this cohort, infection was associated with a dismal long-term prognosis: 60 of 70 patients died over a follow-up period of five years. The rate of C. difficile was 1.05 per 100 dialysis patient years in a UK registry [8]. Colonization with toxigenic C. difficile was higher among chronic kidney disease (CKD) patients in Australia with a relative risk (RR) of 5.78 (95% CI 2.29-14.59) [39].

Another study found that the incidence of C. difficile-associated infection was 10.7 per 1000 admissions for patients with CKD compared with 2.7 per 1000 among other patients (p<0.0001) [40]. In this study, symptoms included diarrhea, fever, and ileus or abdominal pain in 89, 53, and 44 percent of renal patients, respectively. ESKD and being on dialysis, as opposed to CKD stages 3 to 5, appears to be a risk factor for C. difficile colitis for unclear reasons [41,42]. A subsequent retrospective review of C. difficile infections in CKD patients again showed those on dialysis to be twice as likely to develop C. difficile infections than non-CKD patients and 1.33 times more likely than nondialysis CKD patients [43]. Interestingly, dialysis patients with C. difficile infection had fewer complications from the infection (colectomy, longer hospitalization, discharge to a health care facility) than those with CKD not on dialysis [43]. A meta-analysis examining 19 studies with 116,875 patients found a higher relative risk of recurrent C. difficile infection (pooled RR 2.73, 95% CI 1.36-5.47), as well as higher mortality in ESKD and CKD patients (RR 1.76, 95% CI 1.32-2.34) [44].

A review of 419,875 incident dialysis patients in United States Renal Data System (USRDS) data from 2005 to 2008 found 4.25 percent of patients diagnosed with C. difficile infection [45]. Most had either a hospital or intensive care unit (ICU) stay within 90 days. Risk factors for C. difficile infection included age ≥65 years of age (RR 1.76), human immunodeficiency virus (HIV; RR 2.68), and a history of bacteremia (RR 1.74). The relative risk of death was higher in those with cirrhosis (RR 1.76) and those older than 65 years of age (RR 2.28). Recurrent C. difficile occurred in 23.6 percent, more commonly in White Americans [45].

Management of C. difficile colitis in dialysis patients is similar to the regimen used in nondialysis patients but with minor dosing adjustments [46]. It is recommended that dialysis patients with estimated glomerular filtration rates of less than 10 mL/min receive a 50 percent dose reduction of metronidazole [47]; the drug should be administered after hemodialysis [47] (see "Clostridioides difficile infection in adults: Treatment and prevention"). The rise in cases of C. difficile has been accompanied by a resistance to treatment. This has led to the development of alternative treatment strategies for resistant cases. (See "Clostridioides difficile infection in adults: Treatment and prevention".)

GENITOURINARY INFECTION — The clinical presentation of urinary tract infection in a dialysis patient with residual urine production is similar to that of an individual without kidney disease. By comparison, anuric patients may present with only bladder discomfort and/or fever.

The presence of pyuria, including white blood cell casts, without bacterial infection is common in dialysis patients. Some investigators have suggested that pyuria is a marker for urinary tract infection, even in asymptomatic dialysis-dependent patients. The literature is sparse and conflicting concerning this issue. One study of 25 chronic hemodialysis patients reported no correlation between a predominance of white blood cells and white blood cell casts in the urinalysis and the presence of infection [48]. By comparison, another report of asymptomatic dialysis patients suggested that pyuria (defined by greater than 10 white blood cells per high-power field) was associated with a propensity for urinary tract infection [49]. In this report, urine cultures of 7 of 10 asymptomatic dialysis patients with significant pyuria grew possible urinary pathogens compared with only 4 of 18 with insignificant pyuria.

A subsequent study of asymptomatic patients (11 hemodialysis and 11 peritoneal dialysis) found a poor correlation between significant pyuria (defined as above) and positive urine cultures [50]. Eight of nine patients with significant pyuria and 10 of 11 patients without significant pyuria grew one or more pathogens considered clinically significant. The urine cultures of only two patients, one from each group, grew a significant pathogen, thereby suggesting that even significant pyuria does not strongly correlate with the presence of infection.

Similar findings were found in a study of 43 asymptomatic peritoneal dialysis patients [51]. Of the 12 patients found on culture to be infected, 67 percent had pyuria. By contrast, among noninfected patients, 13 percent had pyuria.

In a review of the small body of literature dealing with this issue, it was concluded that asymptomatic pyuria is common in dialysis patients (30 to 40 percent). However, its presence does not necessarily indicate a true infection, with the correlation being quite variable (11 to 70 percent) [52].

Thus, asymptomatic pyuria is of unclear significance in dialysis patients. Establishing the diagnosis of a urinary tract infection in this setting requires a positive urine culture.

Urinary tract infections are the most common nosocomial infections among hospitalized chronic dialysis patients who have undergone urinary catheterization. They appear to be responsible for nearly one-half of such infections, with Candida being the most frequently observed pathogen [53].

Treatment — Management of symptomatic urinary tract infection must be tailored to the individual dialysis patient and the cultured organism. (See "Acute simple cystitis in females".)

Pyocystis — Pyocystis, defined as a large collection of pus in a nonfunctioning bladder, may occur in anuric dialysis patients; it is an overlooked cause of fever in this patient population. In this setting, culture most commonly yields multiple organisms. Treatment usually consists of bladder irrigation with antimicrobial solutions and possibly antimicrobial therapy, depending upon the virulence of the pathogen and the clinical state of the patient.

Pyelonephritis — The presentation of pyelonephritis in the patient with and without kidney disease is similar; symptoms or signs may include fever, abdominal pain, dysuria (if not anuric), and flank pain. Patients with end-stage kidney disease (ESKD) due to polycystic kidneys and/or older dialysis patients may be at increased risk. (See "Autosomal dominant polycystic kidney disease (ADPKD): Evaluation and management of complicated urinary tract infections".)

As with a urinary tract infection, treatment of the patient with pyelonephritis is based upon the clinical characteristics of the patient and microbiologic results (see "Acute simple cystitis in females"). The treatment of renal infection in the patient with polycystic kidneys is presented separately. (See "Autosomal dominant polycystic kidney disease (ADPKD): Evaluation and management of complicated urinary tract infections".)

SKIN AND BONE INFECTIONS — Cellulitis and osteomyelitis are significant causes of morbidity in patients on dialysis.

Cellulitis — Cellulitis frequently occurs in the diabetic patient on dialysis with neurologic and peripheral vascular disease and is an important cause of morbidity in patients on dialysis. Diabetic foot infection poses a serious risk for amputation and must be promptly identified and treated (see "Management of diabetic foot ulcers"). The duration of treatment among these patients is often longer than for immunocompetent nondialysis patients. (See "Acute cellulitis and erysipelas in adults: Treatment".)

Osteomyelitis — Osteomyelitis may result from direct extension of cellulitis, which, as mentioned, is a common occurrence in diabetics, and via hematogenous spread caused by the failure to recognize and remove infected central venous hemodialysis catheters and/or chronic access. A high index of suspicion is therefore appropriate in dialysis patients, particularly diabetics (see "Approach to imaging modalities in the setting of suspected nonvertebral osteomyelitis"). As with nondialysis patients, treatment is based upon cultured pathogens (when available) and/or empiric regimens. (See "Nonvertebral osteomyelitis in adults: Clinical manifestations and diagnosis".)

Infection and calciphylaxis — Calciphylaxis, a rare complication of the skin microvasculature, affects an estimated 1 percent of patients with end-stage kidney disease (ESKD) per year (see "Calciphylaxis (calcific uremic arteriolopathy)"). This disorder is associated with extensive microvascular calcification and occlusion with thrombosis of the skin, thereby resulting in characteristic violaceous skin lesions. Progression to nonhealing ulcers and sepsis is confounded by secondary infection, which also leads to bloodborne infection and often death [54].

METHICILLIN-RESISTANT STAPHYLOCOCCUS AUREUS — S. aureus bacteremia is common in hemodialysis patients; it is usually related to the presence of an indwelling dialysis catheter or arteriovenous graft and/or peritonitis. The widespread use of vancomycin in dialysis patients has resulted from the convenience of infrequent dosing related to hemodialysis treatments and the recognition that Staphylococcus species cultured from these populations were often resistant to methicillin, thereby leaving vancomycin as the only drug known to cure methicillin-resistant S. aureus (MRSA) [55]. In 2005, the incidence of invasive MRSA infection was 45.2 cases per 1000 dialysis patients compared with a rate of 0.2 to 0.4 cases per 1000 in the general population [56].

However, relatively low rates of MRSA are generally seen in hemodialysis outpatients. In one study of 198 such patients, the rate of MRSA colonization was 5.6 percent [57]. MRSA colonization was increased in those with prior MRSA exposure. A United Kingdom Registry of dialysis patients found MRSA bacteremia of 0.15 episodes per 100 dialysis patients, a relatively stable rate [8].

Many Staphylococcus infections in peritoneal dialysis patients are actually Staphylococcus epidermidis; this is a less virulent pathogen but one that is also often resistant to methicillin (MRSE). Because vancomycin has been widely used as empiric therapy for the past decade, there is concern about the enhanced incidence of infection resulting from vancomycin-resistant Enterococcus (VRE) [58]. (See "Microbiology and therapy of peritonitis in peritoneal dialysis".)

VANCOMYCIN-RESISTANT ENTEROCOCCUS — The emergence of vancomycin-resistant Enterococcus (VRE) and the rising incidence of VRE infection/colonization pose significant health care risks:

Colonization of this organism can evolve into serious infection.

Resistance may be passed to more virulent organisms such as S. aureus.

The carriage of VRE may render the dialysis patient unacceptable for kidney transplantation.

VRE bacteremia predominantly affects severely ill patients who have previously received extensive antibiotic therapy [59]. Dialysis patients, with their propensity for access infection and comorbid conditions requiring prolonged hospitalization, are particularly at risk; however, dialysis vintage has not been found to correlate with the presence of VRE, nor has an increased risk of death been observed in VRE-positive patients [60].

In a meta-analysis of observational studies including nearly 5000 dialysis patients, approximately 6 percent were found to be colonized with VRE [61]. Risk factors for VRE colonization included hospitalization in the recent past and prior use of antibiotics. Patients colonized with VRE had a higher risk of infection with VRE (odds ratio 21.6, 95% CI 5.3-81.6).

Centers for Disease Control and Prevention (CDC) guidelines mandate that VRE-positive hemodialysis patients must be isolated during treatment and hospitalizations [62,63]. The acquisition of VRE is also of particular concern among peritoneal dialysis patients. This is discussed separately. (See "Microbiology and therapy of peritonitis in peritoneal dialysis".)

Linezolid, an antimicrobial used in the treatment of VRE infections, is not well suited as long-term therapy, because myelosuppression (including anemia, leukopenia, pancytopenia, and thrombocytopenia) can develop in patients receiving linezolid for more than two weeks. Such adverse hematologic effects may be more common in dialysis patients. As an example, in a retrospective case-control study, patients with ESKD, compared with those without renal disease, had a significantly higher rate of linezolid-associated thrombocytopenia (79 versus 43 percent) and anemia (72 versus 37 percent) [64].

The treatment of VRE is presented separately. (See "Treatment of enterococcal infections".)

TUBERCULOSIS — Although very few early reports were published, the incidence of tuberculosis in patients undergoing dialysis was considered to be relatively low. However, it appears that dialysis patients have an enhanced risk for developing tuberculosis. As an example, a 12-year study of 110 hemodialysis patients found an incidence of 24 percent, with the majority of patients having pulmonary involvement (70 percent) [65]. With early therapy, all patients survived and developed no recurrence within five years of follow-up. Similar findings have been noted in other reports [66,67]. However, in an epidemiologic study, end-stage kidney disease (ESKD) was associated with an increased risk of death in older patients with tuberculosis with a 32.7 percent mortality [68]. Other than attention to appropriate dosing regimens for those with ESKD, the treatment of tuberculosis in dialysis patients is the same as for nondialysis patients. (See "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults without HIV infection".)

There is a heightened awareness of the propensity for immunosuppressed patients, including those on dialysis, to reactivate old or acquire new tuberculosis infections. In a single dialysis center, for example, one infected health care worker apparently transmitted tuberculosis to 29 patients [69].

Affected patients frequently present with fever, anorexia, and weight loss [70]. Involvement of extrapulmonary organs is also common, particularly the lymphatic system and peritoneum [71-73].

Since approximately 30 to 40 percent or more of hemodialysis patients are anergic, additional clinical testing for the presence of tuberculosis may be appropriate in patients for whom the index of suspicion is high [74-80]. The interferon (IFN)-gamma release assay (IGRA) has been useful for the diagnosis of tuberculosis in nondialysis patients. A number of studies have also been published suggesting that the IGRA is also useful in dialysis patients [81-83]. IGRA tests for latent tuberculosis may be advisable in areas where there is a moderate to high burden of tuberculosis as these tests correlate better than skin testing with the risk of tuberculosis infection and past tuberculosis disease [83]. Although some advocate IGRA for tuberculosis screening in dialysis patients [82], the practice has not yet gained widespread acceptance [82]. (See "Tuberculosis infection (latent tuberculosis) in adults: Approach to diagnosis (screening)".)

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".)

SUMMARY AND RECOMMENDATIONS

Infections are a leading cause of death among patients with end-stage kidney disease (ESKD), accounting for approximately 9 to 14 percent of all fatalities. Access-related infections are the most common and respiratory tract infections are the second most common causes of infection-related deaths. Others include human immunodeficiency virus (HIV) infection, infections of the central nervous system, gastrointestinal tract, genitourinary tract, skin (cellulitis), and bone (osteomyelitis). (See 'Epidemiology' above.)

Dialysis patients treated with deferoxamine are at increased risk of mucormycosis, a life-threatening fungal disease that most commonly occurs in immunocompromised and diabetic patients. (See 'Mucormycosis' above.)

Peritonitis is common in patients undergoing peritoneal dialysis but is usually easily treatable. Peritonitis caused by enteric bacteria is frequently caused by injury to gastrointestinal viscera and may have devastating consequences. (See 'Visceral leakage causing peritonitis' above and "Microbiology and therapy of peritonitis in peritoneal dialysis".)

Infectious hepatitis, particularly with hepatitis B and C, is a significant cause of morbidity and mortality in hemodialysis patients, with hepatitis C being a leading cause of liver disease. The incidence of both hepatitis B and C infections is declining in this patient population. (See 'Hepatitis' above and "Hepatitis C virus infection in patients on maintenance dialysis" and "Hepatitis B virus and dialysis patients".)

Dialysis patients are particularly susceptible to Clostridioides difficile colitis since they are commonly administered antibiotics. Mortality and recurrent infections are more common in ESKD patients than others with C. difficile colitis. Management of C. difficile colitis in dialysis patients is similar to the regimen used in nondialysis patients but with dosing adjustments. (See 'Clostridioides difficile colitis' above.)

Urinary tract infections are the most common nosocomial infections among hospitalized chronic dialysis patients who have undergone urinary catheterization. Candida is the most frequently observed pathogen. The management of symptomatic urinary tract infection must be tailored to the individual dialysis patient and the cultured organism. (See 'Genitourinary infection' above and "Acute simple cystitis in females".)

Cellulitis is common in the diabetic dialysis patient with neurologic and peripheral vascular disease and poses risk for complications, including amputation. Osteomyelitis may result from direct extension of cellulitis or via hematogenous spread from an infected central venous hemodialysis catheters and/or chronic access. (See 'Skin and bone infections' above and "Approach to imaging modalities in the setting of suspected nonvertebral osteomyelitis".)

Staphylococcus aureus bacteremia is common in hemodialysis patients and is usually related to the presence of an indwelling dialysis catheter or arteriovenous graft and/or peritonitis. Invasive methicillin-resistant S. aureus (MRSA) infection is more common in the hemodialysis population compared with the general population, but relatively low rates of MRSA are generally seen in hemodialysis outpatients. (See 'Methicillin-resistant staphylococcus aureus' above.)

Vancomycin-resistant Enterococcus (VRE) colonization is not common among hemodialysis outpatients. Centers for Disease Control and Prevention (CDC) guidelines mandate that VRE-positive hemodialysis patients must be isolated during treatment and hospitalizations. The carriage of VRE may render the dialysis patient unacceptable for kidney transplantation. (See 'Vancomycin-resistant enterococcus' above and "Microbiology and therapy of peritonitis in peritoneal dialysis".)

Dialysis patients have an enhanced risk for developing tuberculosis. Other than attention to appropriate dosing regimens for those with ESKD, the treatment of tuberculosis in dialysis patients is the same as for nondialysis patients. (See 'Tuberculosis' above and "Treatment of drug-susceptible pulmonary tuberculosis in nonpregnant adults without HIV infection".)

Herpes zoster is more common in hemodialysis patients than in the general population and vaccination is recommended. Treatment with antiviral agents such as valacyclovir requires adjustment in dose for dialysis patients. (See 'Herpes zoster' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Jean L Holley, MD, FACP, who contributed to an earlier version of this topic review.

  1. United States Renal Data System. Excerpts from the USRDS 2009 annual data report: Atlas of end-stage renal disease in the United States. Am J Kidney Dis 2010; 55(Suppl 1):S1.
  2. United States Renal Data System. 2016 USRDS annual data report: Epidemiology of kidney disease in the United States. National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 2016.
  3. Survival, mortality, & causes of death. USRDS. United States Renal Data System. Am J Kidney Dis 2001; 38:S135.
  4. United States Renal Data System. USRDS 2018 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States. National Institutes of Health, editor, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 2018. https://www.usrds.org/2014/view/.
  5. United States Renal Data System. USRDS 2020 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States. National Institutes of Health; National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 2020.
  6. Naqvi SB, Collins AJ. Infectious complications in chronic kidney disease. Adv Chronic Kidney Dis 2006; 13:199.
  7. Dalrymple LS, Katz R, Kestenbaum B, et al. The risk of infection-related hospitalization with decreased kidney function. Am J Kidney Dis 2012; 59:356.
  8. Evans R, Caskey F, Fluck R, et al. UK Renal Registry 18th Annual Report: Chapter 12 Epidemiology of Reported Infections amongst Patients Receiving Dialysis for Established Renal Failure in England 2013 to 2014: a Joint Report from Public Health England and the UK Renal Registry. Nephron 2016; 132 Suppl 1:279.
  9. Ishigami J, Matsushita K. Clinical epidemiology of infectious disease among patients with chronic kidney disease. Clin Exp Nephrol 2019; 23:437.
  10. Ishigami J, Grams ME, Chang AR, et al. CKD and Risk for Hospitalization With Infection: The Atherosclerosis Risk in Communities (ARIC) Study. Am J Kidney Dis 2017; 69:752.
  11. Sarnak MJ, Jaber BL. Mortality caused by sepsis in patients with end-stage renal disease compared with the general population. Kidney Int 2000; 58:1758.
  12. Foley RN, Guo H, Snyder JJ, et al. Septicemia in the United States dialysis population, 1991 to 1999. J Am Soc Nephrol 2004; 15:1038.
  13. Khan IH, Catto GR. Long-term complications of dialysis: infection. Kidney Int Suppl 1993; 41:S143.
  14. Alexander D, Peacock E. Drug resistant organisms and their implications for the outpatient dialysis setting. Nephrol News Issues 1997; 11:27.
  15. Calfee DP. Multidrug-resistant organisms within the dialysis population: a potentially preventable perfect storm. Am J Kidney Dis 2015; 65:3.
  16. Mc Causland FR, Brunelli SM, Waikar SS. Association of smoking with cardiovascular and infection-related morbidity and mortality in chronic hemodialysis. Clin J Am Soc Nephrol 2012; 7:1827.
  17. Slinin Y, Foley RN, Collins AJ. Clinical epidemiology of pneumonia in hemodialysis patients: the USRDS waves 1, 3, and 4 study. Kidney Int 2006; 70:1135.
  18. Sibbel S, Sato R, Hunt A, et al. The clinical and economic burden of pneumonia in patients enrolled in Medicare receiving dialysis: a retrospective, observational cohort study. BMC Nephrol 2016; 17:199.
  19. James MT, Quan H, Tonelli M, et al. CKD and risk of hospitalization and death with pneumonia. Am J Kidney Dis 2009; 54:24.
  20. Guo H, Liu J, Collins AJ, Foley RN. Pneumonia in incident dialysis patients--the United States Renal Data System. Nephrol Dial Transplant 2008; 23:680.
  21. Chen CH, Hsu WH, Chen HJ, et al. Different bacteriology and prognosis of thoracic empyemas between patients with chronic and end-stage renal disease. Chest 2007; 132:532.
  22. Lerner PI. Meningitis caused by Streptococcus in adults. J Infect Dis 1975; 131 Suppl:S9.
  23. Mansoor GA, Ornt DB. Cryptococcal peritonitis in peritoneal dialysis patients: a case report. Clin Nephrol 1994; 41:230.
  24. Smith JW, Arnold WC. Cryptococcal peritonitis in patients on peritoneal dialysis. Am J Kidney Dis 1988; 11:430.
  25. Yinnon AM, Solages A, Treanor JJ. Cryptococcal peritonitis: report of a case developing during continuous ambulatory peritoneal dialysis and review of the literature. Clin Infect Dis 1993; 17:736.
  26. McDonald JR, Zeringue AL, Caplan L, et al. Herpes zoster risk factors in a national cohort of veterans with rheumatoid arthritis. Clin Infect Dis 2009; 48:1364.
  27. Kuo CC, Lee CT, Lee IM, et al. Risk of herpes zoster in patients treated with long-term hemodialysis: a matched cohort study. Am J Kidney Dis 2012; 59:428.
  28. Wu MY, Hsu YH, Su CL, et al. Risk of herpes zoster in CKD: a matched-cohort study based on administrative data. Am J Kidney Dis 2012; 60:548.
  29. Krueger KM, Ison MG, Ghossein C. Practical Guide to Vaccination in All Stages of CKD, Including Patients Treated by Dialysis or Kidney Transplantation. Am J Kidney Dis 2020; 75:417.
  30. Polo JR, Luño J, Menarguez C, et al. Peritoneal mucormycosis in a patient receiving continuous ambulatory peritoneal dialysis. Am J Kidney Dis 1989; 13:237.
  31. Kang HJ, Ahn JH. The frequencies of disease entities that cause acute abdominal pain in end-stage renal disease: focused on differences between hemodialysis and peritoneal dialysis patients. The Journal of the Korean Society of Emergency Medicine 2020; 31:371.
  32. Hojs R. Cholecystolithiasis in patients with end-stage renal disease treated with haemodialysis: a study of prevalence. Am J Nephrol 1995; 15:15.
  33. Mirza MM, Wall BM. Emphysematous cholecystitis in a CAPD patient. Perit Dial Int 1997; 17:305.
  34. Ishikawa I, Chikamoto E, Nakamura M, et al. High incidence of common bile duct dilatation in autosomal dominant polycystic kidney disease patients. Am J Kidney Dis 1996; 27:321.
  35. Harwell CM, Newman LN, Cacho CP, et al. Abdominal catastrophe: visceral injury as a cause of peritonitis in patients treated by peritoneal dialysis. Perit Dial Int 1997; 17:586.
  36. Pakfetrat M, Malekmakan L, Roozbeh J, et al. Endoscopic findings in hemodialysis patients upon workup for kidney transplantation. Saudi J Kidney Dis Transpl 2020; 31:388.
  37. Moran-Atkin E, Stem M, Lidor AO. Surgery for diverticulitis is associated with high risk of in-hospital mortality and morbidity in older patients with end-stage renal disease. Surgery 2014; 156:361.
  38. Bárány P, Stenvinkel P, Nord CE, Bergström J. Clostridium difficile infection--a poor prognostic sign in uremic patients? Clin Nephrol 1992; 38:53.
  39. Furuya-Kanamori L, Clements AC, Foster NF, et al. Asymptomatic Clostridium difficile colonization in two Australian tertiary hospitals, 2012-2014: prospective, repeated cross-sectional study. Clin Microbiol Infect 2017; 23:48.e1.
  40. Cunney RJ, Magee C, McNamara E, et al. Clostridium difficile colitis associated with chronic renal failure. Nephrol Dial Transplant 1998; 13:2842.
  41. Eddi R, Malik MN, Shakov R, et al. Chronic kidney disease as a risk factor for Clostridium difficile infection. Nephrology (Carlton) 2010; 15:471.
  42. Ramesh MS, Yee J. Clostridioides difficile Infection in Chronic Kidney Disease/End-Stage Renal Disease. Adv Chronic Kidney Dis 2019; 26:30.
  43. Keddis MT, Khanna S, Noheria A, et al. Clostridium difficile infection in patients with chronic kidney disease. Mayo Clin Proc 2012; 87:1046.
  44. Thongprayoon C, Cheungpasitporn W, Phatharacharukul P, et al. Chronic kidney disease and end-stage renal disease are risk factors for poor outcomes of Clostridium difficile infection: a systematic review and meta-analysis. Int J Clin Pract 2015; 69:998.
  45. Tirath A, Tadros S, Coffin SL, et al. Clostridium difficile infection in dialysis patients. J Investig Med 2017; 65:353.
  46. Kelly CP, Pothoulakis C, LaMont JT. Clostridium difficile colitis. N Engl J Med 1994; 330:257.
  47. Gilbert DN, Moellering RC, Sande MA. Table 17. In: The Sanford Guide to Antimicrobial therapy, 28th ed., Sanford, 1998. p.117.
  48. Cabaluna CC, Gary NE, Eisinger RP. Urinalysis in patients on chronic hemodialysis. Urology 1977; 10:103.
  49. Chaudhry A, Stone WJ, Breyer JA. Occurrence of pyuria and bacteriuria in asymptomatic hemodialysis patients. Am J Kidney Dis 1993; 21:180.
  50. Eisinger RP, Asghar F, Kolasa C, Weinstein MP. Does pyuria indicate infection in asymptomatic dialysis patients? Clin Nephrol 1997; 47:50.
  51. Orłowska A, Majdan M, Kozioł-Montewka M, et al. Asymptomatic bacteriuria in patients on continuous ambulatory peritoneal dialysis. Ann Univ Mariae Curie Sklodowska Med 2002; 57:285.
  52. Fasolo LR, Rocha LM, Campbell S, Peixoto AJ. Diagnostic relevance of pyuria in dialysis patients. Kidney Int 2006; 70:2035.
  53. D'Agata EM, Mount DB, Thayer V, Schaffner W. Hospital-acquired infections among chronic hemodialysis patients. Am J Kidney Dis 2000; 35:1083.
  54. Budisavljevic MN, Cheek D, Ploth DW. Calciphylaxis in chronic renal failure. J Am Soc Nephrol 1996; 7:978.
  55. Brumfitt W, Hamilton-Miller J. Methicillin-resistant Staphylococcus aureus. N Engl J Med 1989; 320:1188.
  56. Centers for Disease Control and Prevention (CDC). Invasive methicillin-resistant Staphylococcus aureus infections among dialysis patients--United States, 2005. MMWR Morb Mortal Wkly Rep 2007; 56:197.
  57. Hadley AC, Karchmer TB, Russell GB, et al. The prevalence of resistant bacterial colonization in chronic hemodialysis patients. Am J Nephrol 2007; 27:352.
  58. Holley JL, Bernardini J, Johnston JR, Piraino B. Methicillin-resistant staphylococcal infections in an outpatient peritoneal dialysis program. Am J Kidney Dis 1990; 16:142.
  59. Montecalvo MA, Shay DK, Patel P, et al. Bloodstream infections with vancomycin-resistant enterococci. Arch Intern Med 1996; 156:1458.
  60. Roghmann MC, Fink JC, Polish L, et al. Colonization with vancomycin-resistant enterococci in chronic hemodialysis patients. Am J Kidney Dis 1998; 32:254.
  61. Zacharioudakis IM, Zervou FN, Ziakas PD, et al. Vancomycin-resistant enterococci colonization among dialysis patients: a meta-analysis of prevalence, risk factors, and significance. Am J Kidney Dis 2015; 65:88.
  62. Hospital Infection Control Practices Advisory Committee (HICPAC). Recommendations for preventing the spread of vancomycin resistance. Infect Control Hosp Epidemiol 1995; 16:105.
  63. Medical Review Board Workgroup on VRE. Reducing the spread of vancomycin-resistant enterococcus in the dialysis setting. Mid-Atlantic Renal Coalition, 1996 Report.
  64. Wu VC, Wang YT, Wang CY, et al. High frequency of linezolid-associated thrombocytopenia and anemia among patients with end-stage renal disease. Clin Infect Dis 2006; 42:66.
  65. Cengiz K. Increased incidence of tuberculosis in patients undergoing hemodialysis. Nephron 1996; 73:421.
  66. Taskapan H, Utas C, Oymak FS, et al. The outcome of tuberculosis in patients on chronic hemodialysis. Clin Nephrol 2000; 54:134.
  67. Lui SL, Tang S, Li FK, et al. Tuberculosis infection in Chinese patients undergoing continuous ambulatory peritoneal dialysis. Am J Kidney Dis 2001; 38:1055.
  68. Yen YF, Feng JY, Pan SW, et al. Determinants of mortality in elderly patients with tuberculosis: a population-based follow-up study. Epidemiol Infect 2017; 145:1374.
  69. Centers for Disease Control and Prevention (CDC). Tuberculosis transmission in a renal dialysis center--Nevada, 2003. MMWR Morb Mortal Wkly Rep 2004; 53:873.
  70. Eastwood JB, Corbishley CM, Grange JM. Tuberculosis and the kidney. J Am Soc Nephrol 2001; 12:1307.
  71. Hussein MM, Mooij JM, Roujouleh H. Tuberculosis and chronic renal disease. Semin Dial 2003; 16:38.
  72. Hung KH, Lee CT, Chen JB, Hsu KT. Tuberculous peritonitis in uremic patients. Clin Nephrol 2003; 60:113.
  73. Kriki P, Thodis E, Deftereos S, et al. A tumor-like manifestation of extrapulmonary tuberculosis in a hemodialysis patient. Clin Nephrol 2009; 71:714.
  74. Smirnoff M, Patt C, Seckler B, Adler JJ. Tuberculin and anergy skin testing of patients receiving long-term hemodialysis. Chest 1998; 113:25.
  75. Woeltje KF, Mathew A, Rothstein M, et al. Tuberculosis infection and anergy in hemodialysis patients. Am J Kidney Dis 1998; 31:848.
  76. Korzets A, Gafter U. Tuberculosis prophylaxis for the chronically dialysed patient--yes or no? Nephrol Dial Transplant 1999; 14:2857.
  77. Poduval RD, Hammes MD. Tuberculosis screening in dialysis patients--is the tuberculin test effective? Clin Nephrol 2003; 59:436.
  78. Wauters A, Peetermans WE, Van den Brande P, et al. The value of tuberculin skin testing in haemodialysis patients. Nephrol Dial Transplant 2004; 19:433.
  79. Eleftheriadis T, Tsiaga P, Antoniadi G, et al. The value of serum antilipoarabinomannan antibody detection in the diagnosis of latent tuberculosis in hemodialysis patients. Am J Kidney Dis 2005; 46:706.
  80. Cahuayme-Zuniga LJ, Brust KB. Mycobacterial Infections in Patients With Chronic Kidney Disease and Kidney Transplantation. Adv Chronic Kidney Dis 2019; 26:35.
  81. Winthrop KL, Nyendak M, Calvet H, et al. Interferon-gamma release assays for diagnosing mycobacterium tuberculosis infection in renal dialysis patients. Clin J Am Soc Nephrol 2008; 3:1357.
  82. Segall L, Covic A. Diagnosis of tuberculosis in dialysis patients: current strategy. Clin J Am Soc Nephrol 2010; 5:1114.
  83. Lee SS, Chou KJ, Dou HY, et al. High prevalence of latent tuberculosis infection in dialysis patients using the interferon-gamma release assay and tuberculin skin test. Clin J Am Soc Nephrol 2010; 5:1451.
Topic 1893 Version 33.0

References