Nephrology Hypertension

Medical Management of the Dialysis Patient: Infectious Complications

Does this patient have infectious complications?

What is the scope of the problem?

  • Infection is the second leading cause of mortality in patients with end-stage renal disease (ESRD), next only to cardiovascular disease (Figure 1). Septicemia accounts for most of the infectious deaths

    Mortality caused by sepsis in ESRD patients compared to the general population

  • Annual death rates due to sepsis and pneumonia are significantly higher in dialysis patients as compared to the general population

  • Although the presence of diabetes mellitus confers an additional risk for sepsis-related mortality, it does not influence deaths related to pneumonia in this population

  • Bacterial infections are a major cause of hospitalization in dialysis patients

  • Hospitalization for septicemia is associated with an increased risk of myocardial infarction, congestive heart failure, stroke, and peripheral arterial disease after the original hospitalization

  • The majority of ESRD patients in the United States are on hemodialysis

  • Infections related to vascular access are the most common source of bacteremias in hemodialysis patients

  • Non-access related infections among dialysis patients include infections of the upper and lower respiratory tract, gastrointestinal infections, including hepatitis and Clostridium difficile colitis, genitourinary tract infections, cellulitis and osteomyelitis, infections due to antibiotic-resistant organisms, and tuberculosis

  • Advancing age, diabetes mellitus and uremia as a cause of acquired immune deficiency contribute to the high prevalence of infections in ESRD (United States Renal Data System registry)

  • Other factors that predispose these patients to infections include breaches in sterility during water treatment and distribution and dialysate delivery, dialyzer reuse, and failure to adequately follow maintenance recommendations

What are the clinical characteristics associated with increased infections in dialysis patients?

  • Older age

  • Diabetes mellitus

  • Use of catheters, and to a lesser extent, arterio-venous grafts (AVG) for vascular access

  • Low serum albumin

  • Malnutrition

  • Dialyzer reuse/reprocessing

  • Iron -overload

  • The passage of pyrogens such as bacterial endotoxin across the dialyzer membrane leading to cytokine production

  • This typically presents with fever and chills immediately after the start of the dialysis session. Fever resolves spontaneously after cessation of dialysis

  • Use of high-flux dialyzers and dialyzer reuse are associated with an increased incidence of pyrogenic reactions

  • This must be differentiated from patients with infected hemodialysis catheters who may sometimes develop fever and chills only after commencement of dialysis

  • Blood cultures should always be obtained in any febrile hemodialysis patient even when a pyrogenic reaction is suspected.

Vascular access infections

Septicemia is the leading cause of mortality attributed to infections in dialysis patients, and vascular access infections account for the majority of the cases. Risk factors for septicemia include anemia, vascular access being a catheter or AVG, hypoalbuminemia, dialyzer reuse and previous history of bacteremia.

The incidence of bacteremia is greater in patients with indwelling tunneled catheters than in those with fistulas or synthetic grafts.

Three types of infections are associated with use of tunneled dialysis catheters - exit-site infections, tunnel infections, and catheter related bacteremia (CRB).

An exit site infection is by definition a culture-positive inflammation limited external to the cuff of the tunneled catheter and with negative blood cultures. They respond to topical antibiotics such as mupirocin.

Tunnel infection is culture-positive inflammation within the catheter tunnel with negative blood cultures. It is seen as part of the exit-site infection. Treatment involves removal of the catheter with appropriate parenteral antibiotics.

CRBs are diagnosed based on typical clinical features and typical blood cultures.

Risk factors for CRB include prolonged duration of catheter usage, a history of previous CRB, skin and nasal colonization with staphylococcus, catheter hub colonization, recent surgery, diabetes mellitus, iron overload, immunosuppression, and hypoalbuminemia.

Gram-positive organisms are responsible for most dialysis CRBs. Coagulase-negative staphylococci and S. aureus account for 40-80% of cases. Methicillin-resistant S. aureus (MRSA) has also become an important pathogen in this population.

Non-staphylococcal dialysis CRBs are due predominantly to enterococci or gram-negative rods.

Respiratory infections

  • Respiratory tract infections may be community or hospital acquired

  • Respiratory infections are the second most common infectious cause of death in dialysis patients

  • The incidence of upper respiratory infections is similar to that in the general population; therefore, management is also similar to those for the general population. Careful attention must be paid to drug dosing among patients on dialysis

  • Pneumonia is relatively common among patients on dialysis. The incidence of pneumonia is three- to five-fold higher in patients with advanced chronic kidney disease (CKD) including those on dialysis. Aerobic gram-positive organisms account for over 50% of the cases although gram-negative organisms should be considered in patients dialyzed in a hospital setting.

  • The occurrence of fever, chills, productive cough, pleuritic pain, and shortness of breath should prompt suspicion for an infectious respiratory process. Treatment should be initiated if there is a high index of suspicion before the results of diagnostic tests are available

  • Influenza

    • Dialysis patients should be vaccinated early

    • If symptoms are suggestive of influenza infections, neuraminidase inhibitors should be started promptly

  • Tuberculosis

    • The incidence of both latent and active TB is relatively high among dialysis patients

    • Typical symptoms include fever, anorexia, night sweats and unexplained weight loss

    • Extrapulmonary involvement is relatively common compared to the general population

Urinary tract infections

  • Among patients on dialysis who retain significant urine production, the clinical presentation of urinary tract infections (UTI) is similar those without kidney disease. Among anuric dialysis patients, lower abdominal discomfort and fever may be the only presenting symptoms of a UTI

  • Pyuria without bacterial infections is common and is of uncertain significance. Establishing the diagnosis of a UTI in these patients requires a positive urine culture

  • Urinary tract infections, especially with Candida, are the most common nosocomial infections among dialysis patients in hospitals who have undergone bladder catheterization

  • Management of symptomatic UTI is similar to that in the general population, but with antibiotic dose adjustment

  • Pyocystis, a large collection of pus in a non-functioning bladder may occur in dialysis patients who are anuric or who have a neurogenic bladder. Urine culture often yields a polymicrobial growth. Treatment usually involves bladder irrigation with appropriate antibacterial solutions and, where appropriate, systemic antibiotic therapy

Clostridium difficile colitis

  • Given their frequent exposure to antibiotics, dialysis patients are susceptible to Clostridium difficile colitis.

  • Compared to non-dialysis patients, morbidity and mortality associated with C. difficile infection is higher among dialysis patients

  • Management of C. difficile colitis in dialysis patients is similar to that in non-dialysis patients. However it is recommended that hemodialysis patients receive a 50% reduced dose of metronidazole and the antibiotic should be administered after hemodialysis

Methicillin-resistant Staphylococcus aureus (MRSA)

  • S. aureus infection is common in dialysis patients and usually secondary to intravascular catheters, AV grafts, or peritonitis.

  • Rates of MRSA infections among dialysis patients are relatively high compared to non-dialysis patients and are approximately 5-6% in this population. Colonization rates are higher with prior MRSA exposure

Vancomycin-resistant enterococcus

  • VRE bacteremia tends to affect patients with severe illness who have received prolonged or frequent courses of antibiotics. Although dialysis patients are at particular risk, studies indicate that the incidence of VRE in dialysis patients is no higher than among non-dialysis subjects

  • Rates of VRE colonization are relatively low in hemodialysis patients, with colonization more likely among those with more frequent hospitalizations and prior VRE exposure

Hepatitis C

  • Liver disease related to hepatitis C can cause significant morbidity and mortality among patients with ESRD on maintenance dialysis

  • The prevalence of anti-HCV antibody among patients on dialysis is higher than in healthy populations, suggesting that dialysis patients may be at higher risk of acquiring HCV infection

  • Using third generation assays for anti-HCV antibody, the prevalence of anti-HCV antibodies among dialysis patients is approximately 5% to 10% in the United States

  • Risk factors for HCV infection among dialysis patients include, the number of blood transfusions, the duration of end-stage renal disease (ESRD), the mode of dialysis (PD patients have a lower prevalence compared to hemodialysis patients), and the prevalence of HCV infection in the dialysis unit. Other risk factors include a history of prior organ transplantation, intravenous drug abuse, and male gender

  • Both the CDC and K-DIGO do not recommend dedicated machines, patient isolation, or a ban on reuse in HD patients with HCV infection. However, strict adherence to "universal precautions", careful attention to hygiene, and strict sterilization of dialysis machines is recommended

  • The CDC recommends that all HD patients should be tested for anti-HCV on admission. Subsequently, anti-HCV negative patients should be tested for anti-HCV antibodies semi-annually

  • Factors that may affect the risk of transmission of HCV to patients and staff in hemodialysis units include transmission needle-stick injuries, breakdown in standard infection control practices, and physical proximity to an infected patient

  • Cure of HCV infections is now possible with the approval of several direct-acting retrovirals. However, decisions to initiate antiviral therapy in dialysis patients need to be individualized taking into account the anticipated benefits and risks of HCV therapy.

Hepatitis B

  • Hepatitis B virus (HBV) infection in the dialysis patient can lead to acute or chronic hepatitis, cirrhosis, or hepatocellular carcinoma.

  • The incidence of hepatitis B has declined in the dialysis population since the introduction of strict infection–control strategies, routine screening of patients and staff for hepatitis B virus surface antigen (HBsAg) and anti–HBs antibody, vaccination of patients and staff, use of separate rooms and dedicated machines for hemodialysis of HBsAg positive patients, and prohibition of dialyzer reuse in HBsAg positive patients

  • In the majority of dialysis patients, testing for HBsAg is sufficient for the diagnosis of HBV infection. However, a negative HBsAg test does not preclude absolutely the presence of occult HBV infection

  • The clinical features of chronic hepatitis B or HBV-induced cirrhosis in dialysis patients are identical to those without advanced kidney disease. Aminotransferase levels indicate hepatic activity, but need to be interpreted according to the adjusted normal range, which is lower in patients on long-term dialysis.

HIV

  • The incidence of HIV infection in the dialysis population varies according to the demographic profile of the local dialysis population. Nonetheless, the incidence of HIV infection in the dialysis population overall is higher than among the general population

  • We recommend confidential, voluntary HIV testing of all dialysis patients. However, routine HIV testing may be associated with an increased incidence of false-positive results

  • HIV transmission in the dialysis setting is uncommon. It can be avoided by strict adherence to standard infection control procedures. The CDC states that no special isolation of HIV-positive dialysis patients is necessary.

  • Dialyzer reuse must be avoided in HIV positive patients on hemodialysis

  • The use of antiretroviral therapy (ART) is the single most important intervention for an HIV-infected patient with ESRD.

  • ART is associated with decreased mortality in dialysis patients.

  • Careful attention must be paid to appropriate dosing of ART in dialysis patients to avoid medication toxicity or inadequate virologic control

What tests to perform?

CRBs

CDC recommends one of two culture techniques for diagnosing CRBs

  • Paired quantitative blood cultures from the catheter and peripheral vein ( ratio of >5:1 considered definitive for catheter as source of infection)

  • Paired qualitative blood cultures from the catheter and peripheral vein observing differential time to positivity (DTP). Catheter is considered as the source if the culture from the catheter is positive by about 2 hours before the peripherally drawn culture

Neither are practiced routinely in clinical practice. When the pre-test probability is high, routine blood cultures have sensitivity and specificity of more than 75%

Diagnostic difficulties among dialysis patients

  • Poor peripheral venous access or the need to preserve an existing vein for future fistula or graft creation may make obtaining peripheral blood cultures difficult

  • If symptoms/signs occur during a dialysis session, samples drawn from catheters or dialysis tubing may suffice, as systemic blood is circulating through the extracorporeal system

Respiratory infections

Diagnosis may be difficult as delayed skin hyperreactivity to tuberculin antigen may be diminished or absent because of cutaneous anergy in approximately 30 to 40% of dialysis patients.

Some experts recommend that Interferon-Gamma Release Assays (IGRAs) may be useful in the diagnosis of tuberculosis in dialysis patients. These are whole-blood tests that can aid in diagnosing Mycobacterium tuberculosis infection. They do not help differentiate latent tuberculosis infection from tuberculosis disease. Two IGRAs that have been approved by the U.S. Food and Drug Administration (FDA) are commercially available in the U.S: QuantiFERON®-TB Gold In-Tube test (QFT-GIT) and T-SPOT®.TB test (T-Spot)

Hepatitis C

The CDC recommends that all HD patients should be tested for anti-HCV on admission. Subsequently, anti-HCV negative patients should be tested for anti-HCV antibodies semi-annually.

Hepatitis B

In the majority of dialysis patients, testing for HBsAg is sufficient for the diagnosis of HBV infection. However, a negative HBsAg test does not preclude absolutely the presence of occult HBV infection

HIV

We recommend confidential, voluntary HIV testing of all dialysis patients. However, routine HIV testing may be associated with an increased incidence of false-positive results

How should patients with infectious complications be managed?

What are the preventive measures against infectious complications in dialysis patients?

  • Strict adherence to the AAMI guidelines for bacteriologic and endotoxin levels in water and dialysate

  • Promote fistula first initiative

  • Switch to a single use dialyzer wherever possible

  • Hold intravenous use of iron preparations during episodes of bacteremia

  • Best practices such as good hand hygiene and aseptic techniques for accessing the vascular access

    • Tunneled dialysis catheter hub contamination during time of use is one of the most important risk factors for catheter-related bacteremia, and can be prevented by following strict protocols in the dialysis unit including mask use by both provider and patient.

    • Nurses and technicians should routinely use hand hygiene and wear non-sterile gloves and a mask when dialysis catheters are accessed. Hand hygiene must precede and follow donning and removal of gloves, respectively, to minimize contamination.

    • The patient should also wear a mask during connection to and disconnection of the catheter and dialysis tubing

Tunneled, cuffed dialysis catheters

  • Cleansing agents

    • For tunneled catheters, the exit site must be cleansed at each dialysis session prior to beginning the treatment with chlorhexidine 2% with 70% alcohol

  • Topical antimicrobial agents.

    • Topical antibiotic use lowers bacteremia rate, exit site infection rate, infection-related hospitalizations, and requirement for catheter removal.

    • The emergence of resistance to topical antimicrobial agents is a potential risk with this approach. Emergence of bacterial strains resistant to mupirocin has been reported in both the United States and Canada.

    • Despite this risk, use povidone iodine antiseptic ointment or bacitracin/gramicidin/polymyxin B ointment at catheter exit site after catheter insertion and at the end of each dialysis session has been recommended by a joint working group led by the Society of Critical Care Medicine and the Infectious Diseases Society of America

  • Catheter exit sites should be covered in dressings, either gauze or transparent semipermeable polyurethane dressings.

  • Catheter Lock Solutions.

    • A systematic review in 2009 found that antimicrobial locks were associated with decreased rates of catheter-related bacteremia and exit site infections.

    • Various antibiotics such as ciprofloxacin, gentamicin, minocycline and vancomycin have been used. These are used in combination with anticoagulants such as heparin, tPA, and citrate

    • Potential problems with this approach include development of antibiotic-resistant organisms when used for longer than six months, toxicities from systemic leakage of these agents such as ototoxicity with gentamicin locks, and rarely severe hypocalcemia with concentrated citrate locks.

    • In the United States, these agents are not approved by the FDA for these indications.

    • Current reimbursement models in the US do not provide payment for these agents, placing a financial burden on dialysis units

    • Therefore, we do not advise using antibiotic-lock solutions for prevention of catheter-related bacteremia, particularly for use beyond six months.

  • Surface treated catheters

    • Antithrombotic coatings

      • Heparin

    • Antimicrobial coatings

      • Silver sulfadiazine

      • Chlorhexidine

      • Minocycline/ Rifampin

      • Ciprofloxacin

    • Data for efficacy only exists in critical care settings and with short term use

  • Patients with tunneled dialysis catheters should be discouraged from using showers

Immunization/Vaccination in dialysis patients

  • The antibody response to a number of commonly used vaccines is suboptimal in dialysis patients. It appears that disturbances in T lymphocytes and antigen-presenting cells may be responsible for the altered acquired immunity in ESRD patients.

  • Nonetheless, vaccination against hepatitis B, influenza, pneumococcus, and tetanus/diphtheria are indicated for almost all dialysis patients. Dosage of these vaccines, other than for hepatitis B, is similar to that used in the general population.

    • Hepatitis B

      • Approximately 50 to 60 percent of dialysis patients develop antibodies following HBV vaccination.

      • Hemodialysis patients vaccinated against hepatitis B have a 70 percent lower risk for infection compared with non-vaccinated patients

      • The following strategies may be used to maximize antibody response to the vaccine

        • Double the vaccine dose suggested for patients without ESRD (ie, 40 µg/dose in patients with ESRD)

        • The vaccine should be administered intramuscularly

        • 40 µg IM should be given zero, one, and six months (Heptavax) or zero, one, two, and six months (Engerix)

        • Ideally, vaccination series should begin as soon as the need for dialysis initiation is anticipated in patients with advanced CKD.

        • Testing for HBsAg should be avoided within three weeks of the vaccination

        • Patients who mount an inadequate antibody response (titers <10 IU/L), should be administered a second three dose series

    • Pneumococcus

      • As with other vaccines, response to pneumococcal vaccination is suboptimal in ESRD patients. Dosage is identical to that used in the general population and revaccination is dependent on the antibody response

    • Influenza

      • Influenza vaccination is recommended annually

    • Tetanus, diphtheria

      • A booster dose every 10 yr is recommended

CRBs

Empiric antibiotic therapy

Among dialysis patients with suspected CRB, empiric broad-spectrum antibiotic therapy to cover both gram-positive and gram-negative organisms must be initiated soon after blood cultures have been drawn.

Vancomycin is administered for gram-positive coverage until speciation and sensitivities become available. Daptomycin may be substituted in patients with a documented vancomycin allergy. Ceftazidime is administered for gram-negative coverage. An alternative option is gentamicin, although the frequency of aminoglycoside ototoxicity is relatively high in this population.

In outpatients, vancomycin may be administered at a dose of 1 to 1.5 g as a loading dose during the last 60 minutes of the dialysis session, followed by 500 mg in the last 30 to 60 minutes of subsequent dialysis sessions. Among inpatients, subsequent dosing can be administered post-dialysis, guided by plasma levels. Daptomycin may be administered at a dose of 7-9 mg/kg during the last 30 minutes of each dialysis session (or immediately after a dialysis session in inpatients). Intravenous ceftazidime 2g should be given after each hemodialysis session.

Subsequent treatment

Once the organism and its sensitivities have been obtained, treatment must be tailored accordingly. The ability to administer an antibiotic with and/or after each dialysis session is an important consideration, particularly in outpatients.

  • Methicillin-resistant staphylococcus aureus (MRSA): Vancomycin can be continued. Patients with vancomycin allergy can be treated with daptomycin.

  • Methicillin-sensitive staphylococcus (MSSA): Vancomycin should be substituted with Cefazolin 20 mg/kg after each dialysis session. Vancomycin is preferred for patients who are allergic to penicillin/cephalosporins.

  • Vancomycin-resistant enterococcus (VRE). Daptomycin can be used to treat VRE.

  • Gram-negative organisms. 95% of gram-negative bacteria isolated in the setting of CRB are sensitive to both third-generation cephalosporins and aminoglycosides. Ceftazidime can be continued if an infection with gram-negative bacteria is confirmed. For extended-spectrum beta lactamase producing organisms, a carbapenem such as ertapenem or meropenem may be used.

  • Candidemia. The isolation of Candida species requires catheter removal and treatment with an appropriate antifungal agent.

Monitoring

  • Repeat blood cultures 48-72 hours after the initiation of antibiotic therapy

  • If repeat blood cultures are positive, catheter removal and additional evaluation for metastatic infection or endocarditis is recommended

  • Echocardiograms in all patients with S. aureus bacteremia that persists on blood cultures drawn 48-72 h after initiation of therapy

Duration of antibiotic therapy

  • In uncomplicated CRB, if the infected catheter has been removed, replaced with a new catheter, and surveillance blood cultures are negative, two to three weeks

  • In uncomplicated CRB, if the infected catheter has been treated with an antibiotic lock solution, three weeks

  • If there is evidence of metastatic infection or if surveillance blood cultures remain positive after three or more days of antibiotic therapy, six to eight weeks of therapy is recommended

Management of the catheter

  • Immediate removal. Best option for achieving cure of the infection. This may present problems in dialysis delivery in patients with limited access options. Nonetheless, immediate removal of an infected catheter is strongly recommended in the following circumstances: severe sepsis, hemodynamic instability, evidence of metastatic infection, signs of associated exit-site or tunnel infection, persistent fever and/or bacteremia 48-72 hours after initiation of antibiotic therapy to which the organism is sensitive, difficult to treat/eradicate pathogens such as S. aureus, Pseudomonas, Candida, or multi-drug resistant pathogens.

  • After removal of the infected tunneled catheter, a temporary non-tunneled catheter can be placed as a short-term access option for dialysis. A new tunneled catheter can be placed after surveillance blood cultures are negative.

  • Catheter exchange over guidewire. For patients with less severe infections, delayed exchange of the infected catheter over a guidewire for a new catheter can be accomplished after two to three days of effective antibiotic therapy, resolution of fever, and negative surveillance blood cultures.

Antibiotic lock

An alternate option for patients with less severe infections and without indications for immediate catheter removal is the use of an antibiotic lock as adjunctive therapy to systemic antimicrobial therapy. These solutions typically consist of a mixture of an anticoagulant (heparin or citrate) and high concentrations of an antibiotic which is instilled ("locked") into each catheter lumen at the end of each dialysis session for the duration of systemic antibiotic therapy. Some examples of antibiotic lock solutions include:

Vancomycin/heparin

Vancomycin/Ceftazidime/heparin

Ceftazidime/heparin

Cefazolin/heparin

These solutions are prepared immediately before instillation into the catheter lumen, preferably by pharmacists or a trained nurse.

In patients with CRB, there is no role for leaving the catheter in place without either replacing it or using antibiotic lock solutions.

Respiratory infections

  • Respiratory tract infections may be community or hospital acquired

  • Respiratory infections are the second most common infectious cause of death in dialysis patients

  • The incidence of upper respiratory infections is similar to that in the general population; therefore, management is also similar to those for the general population. Careful attention must be paid to drug dosing among patients on dialysis

  • Pneumonia is relatively common among patients on dialysis. The incidence of pneumonia is three- to five-fold higher in patients with advanced chronic kidney disease (CKD) including those on dialysis. Aerobic gram-positive organisms account for over 50% of the cases, but gram-negative organisms should also be considered in patients dialyzed in a hospital setting.

  • The occurrence of fever, chills, productive cough, pleuritic pain, and shortness of breath should prompt suspicion for an infectious respiratory process. Treatment should be initiated if there is a high index of suspicion before the results of diagnostic tests are available

  • Influenza

    • Dialysis patients should be vaccinated yearly

    • If symptoms are suggestive of influenza infections, neuraminidase inhibitors should be started promptly

  • Tuberculosis

    • The incidence of both latent and active TB is relatively high among dialysis patients

    • Presenting symptoms may include fever, anorexia, and unexplained weight loss

    • Extra-pulmonary involvement is also relatively more common compared to the general population

Urinary tract infections

Management of symptomatic UTI is similar to that in the general population, with however, antibiotic dose adjustment.

Clostridium difficile colitis

Management of C.difficile colitis in dialysis patients is similar to that in non-dialysis patients. However it is recommended that hemodialysis patients receive a 50% reduced dose of metronidazole and the antibiotic should be administered after hemodialysis.

Methicillin-resistant Staphylococcus aureus (MRSA)

The use of vancomycin is widespread in dialysis patients, given the high rate of MRSA infections and the convenience of dosing with use of this antibiotic even for methicillin-sensitive S. aureus infections. However, this has raised concern regarding the increased incidence of infections resulting from vancomycin-resistant enterococcus (VRE).

Vancomycin-resistant enterococcus

Linezolid, an antibiotic effective against VRE, can cause myelosuppression (thrombocytopenia, anemia, leukopenia, pancytopenia) when used for longer than two weeks and is not ideal when long-term therapy is indicated. These effects may be more common among patients with ESRD.

Hepatitis C

For HCV-infected patients on maintenance hemodialysis, the 2008 KDIGO guidelines that recommend monotherapy with standard interferon that is dose adjusted for a glomerular filtration rate of less than 15 mL/min per 1.73 m2 still applies. There is limited data regarding dose and treatment duration. A regimen of three million units of interferon alfa-2b administered subcutaneously three times per week for 6 to 12 months (if tolerated) may be used. Close observation for significant side effects is mandatory, and this treatment is suboptimal.

Ribavirin is not recommended for patients with a creatinine clearance below 50 mL/min, as both the drug and its metabolites accumulate, and are not cleared by hemodialysis. Serious toxicity may result from its use in this population.

As there is insufficient data concerning its use in dialysis patients, we do not recommend use of pegylated interferon in these patients unless they are enrolled in a clinical trial.

With the advent of direct-acting retrovirals, there are now very high cure rates for HCV infections in the general population. Unfortunately, there is not sufficient data for many of these new therapies in patients with severe renal impairment. Accordingly, there needs to be a case by case decision regarding treatment in dialysis patients. For genotypes 1 and 4 the option of elbasvir-grazoprevir shows promise for efficacy and safety in severe renal impairment. For now, there is not enough data regarding the use of sofosbuvir (which is renally cleared) containing regimens.

Hepatitis B

Treatment is indicated in HBsAg-positive patients with evidence of disease activity, as indicated by viral replication and abnormal transaminase levels, preferably confirmed by examination of liver histology

Nucleotide or nucleoside analogues are preferred to interferon therapy. Entecavir is the recommended first-line agent (dosed orally) in patients with kidney disease. The doses of all medications must be adjusted appropriately in patients on dialysis

Patients should be screened every 3-6 months routinely for the presence of hepatitis B infection

HIV

  • Dialyzer reuse must be avoided in HIV positive patients on hemodialysis

  • The use of antiretroviral therapy (ART) is the single most important intervention for an HIV-infected patient with ESRD.

  • ART is associated with decreased mortality in dialysis patients.

  • Careful attention must be paid to appropriate dosing of ART in dialysis patients to avoid medication toxicity or inadequate virologic control

What happens to patients with infectious complications?

Impaired host immunity

  • Uremia causes a state of acquired immune deficiency

  • Impaired neutrophil function: Impaired neutrophil chemotaxis, phagocytic capacity, oxidative metabolism, and intracellular bacterial killing, as well as dysregulated apoptosis have been demonstrated. Several uremic retention solutes can affect neutrophil function adversely. These include parathyroid hormone, p-cresol, polyamines, aminoguanidine products, and complement factor D. In addition, repeated exposure of neutrophils to bio-incompatible, complement-activating dialyzer membranes can lead to transient leukopenia, increased expression of adhesion molecules, degranulation, and release of proteolytic enzymes. These interactions might lead to decreased responsiveness to subsequent stimuli, such as bacteremia.

  • Alterations in cell-mediated immunity: Other abnormalities involve cell-mediated immunity due to alterations in T-lymphocyte function. These include lymphopenia, impaired delayed skin reactivity, dysregulated cytokine synthesis, and impaired macrophage Fc receptor function. Alterations in B-lymphocyte function affect humoral immunity and result in decreased immunoglobulin levels and a diminished antibody response to microbial antigens.

  • Iron overload: Several in vitro and clinical studies have linked iron overload to an increased risk of bacterial infections in HD patients. Iron overload has been associated with reduced phagocytic function and impaired bacterial killing. Increased availability of free iron can also stimulate bacterial growth and enhance virulence properties. Therefore, it has been proposed that increased use of parenteral iron preparations may contribute to the incidence of bacterial infections.

Bacterial virulence and adherence properties

  • Virulence genes: Under conditions of high bacterial density, bacteria produce extracellular polysaccharides which interact with transcriptional activators leading to increased expression of virulence genes. These virulence genes facilitate bacterial survival and promote resistance to killing by neutrophils as well as the bactericidal or bacteriostatic effects of antimicrobial agents.

  • Bacterial biofilm: These extracellular polysaccharides also form a "slime" or biofilm in the presence of foreign surfaces such as central venous catheters. The biofilm renders the bacteria less susceptible to antimicrobial agents as it constitutes a barrier between the antimicrobial agent and the bacterial cell wall. Biofilm formation can potentiate the pathogenicity of skin bacterial flora such as coagulase-negative staphylococci.

  • Adherence properties of bacteria: S. aureus commonly adheres to host proteins such as fibronectin commonly present on catheters. Other bacteria, such as coagulase-negative staphylococci directly adhere to polymer surface. Catheters made of polyvinylchloride or polyethylene are less resistant to the adherence of bacteria compared with catheters made of polytetrafluoroethylene, silicone elastomer, or polyurethane.

Dialysis procedure

  • Access Related

    • The access site is related to well over 50% of bacteremias in hemodialysis patients. The incidence of bacteremia is far greater in patients with tunneled, cuffed, double-lumen catheters than among those with fistulas or synthetic AV grafts. Following improvements in design, the frequency of catheter-related bacteremia is significantly less in patients with tunneled versus non-tunneled catheters.

    • Peri-catheter thrombus increases the risk of infection

      • Heparin use to preserve catheter patency induces biofilm formation and increased incidence of catheter-related blood stream infection as compared to r-TPA.

    • Use of Buttonhole technique: The buttonhole technique to cannulate AV fistulae has gained popularity over the last decade in the United States. However, increased fistula infection rates have been reported with use of this technique, particularly in patients who self-cannulate their fistulas.

  • Equipment

    • Water supply

      • Surface water as opposed to ground water contains higher levels of endotoxin, bacteria and other organisms. Disinfectants such as chlorine chloramines reduce the numbers but do not eliminate bacteria in municipal water.

    • Water treatment. The Association for the Advancement of Medical Instrumentation (AAMI) has published guidelines for the chemical and bacteriologic quality of water used to prepare dialysis fluid.

      • Some components of the water treatment system may allow amplification of water bacteria. For example, ion exchangers such as water softeners and deionizers do not remove endotoxins or bacteria and may provide sites for significant bacterial multiplication.

      • Other components such as filters tend to clog and may become reservoirs of gram negative water bacteria and endotoxins. Repeated ultraviolet irradiation for disinfection may lead to multiplication of UV-resistant organisms.

      • Failure to follow recommendations in the maintenance and replacement of filters, reverse osmosis units, according to the manufacturer's specifications might lead to bacterial multiplication.

    • Water Distribution

      • Defects in the delivery system of water following treatment to the dialysis machine may result in bacterial proliferation. These include length and diameter of the distribution pipes, material the pipes are made of and inadequate cleansing and disinfection of storage tanks. These factors may lead to the formation of bacterial biofilms in the distribution system.

  • Dialyzer Reuse. When there is a breakdown in the procedures that are to be followed during the reprocessing of dialyzers, pyrogenic reactions or overt bacterial infections can occur.

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