ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Tunneled hemodialysis catheter-related bloodstream infection (CRBSI): Management and prevention

Tunneled hemodialysis catheter-related bloodstream infection (CRBSI): Management and prevention
Literature review current through: Jan 2024.
This topic last updated: Dec 18, 2023.

INTRODUCTION — Tunneled double-lumen catheters are used for short- and intermediate-term venous access among hemodialysis patients who do not have a permanent arteriovenous access [1]. These catheters are also used for permanent vascular access in patients with limited alternative options for vascular access [1]. (See "Central venous catheters for acute and chronic hemodialysis access and their management".)

Tunneled catheters are associated with a number of complications, in particular catheter-related bloodstream infection (CRBSI). An overview of the treatment and prevention of tunneled hemodialysis CRBSI and exit-site infections is presented in this topic review. Other aspects of CRBSI are presented elsewhere. (See "Tunneled hemodialysis catheter-related bloodstream infection (CRBSI): Epidemiology, pathogenesis, clinical manifestations, and diagnosis".)

Complications related to nontunneled catheters and noninfectious catheter-related complications, such as central vein stenosis and catheter thrombosis, are discussed separately. (See "Central vein obstruction associated with upper extremity hemodialysis access" and "Malfunction of chronic hemodialysis catheters" and "Central venous catheters for acute and chronic hemodialysis access and their management".)

MANAGEMENT — The management of hemodialysis CRBSI includes antimicrobial therapy and definitive catheter management (algorithm 1). Empiric systemic antimicrobial therapy should be initiated immediately after obtaining blood cultures in patients suspected of having a CRBSI. If immediate catheter removal is not indicated, then the catheter should be treated with antibiotic lock therapy (a combination of antibiotics and heparin instilled and retained in the catheter between hemodialysis treatments). Subsequent therapy is tailored to microbiology results.

The initial step in the management depends upon the initial clinical evaluation and the patient's location at the time of onset of symptoms.

Triage in the outpatient dialysis unit — Our initial approach for a patient with a suspected CRBSI is to triage them based upon clinical evaluation and their location at the time of onset of symptoms (algorithm 1).

Among outpatients with a suspected CRBSI, we refer and, when appropriate, arrange for ambulance transport to the emergency department in the following situations:

Patients who are hemodynamically unstable or have signs of severe sepsis (see "Sepsis syndromes in adults: Epidemiology, definitions, clinical presentation, diagnosis, and prognosis" and "Evaluation and management of suspected sepsis and septic shock in adults")

Patients who have symptoms or signs of a metastatic infection

Patients who have clear evidence of an exit-site infection (eg, pus at the exit site)  

Patients who meet the above criteria for an emergency department referral should have their blood cultures drawn, any purulent exit-site drainage sent for culture, and empiric broad-spectrum antimicrobial therapy initiated prior to their departure from the outpatient dialysis unit. Prompt administration of antimicrobial therapy lowers the likelihood that the patient's condition worsens en route to the emergency department. (See "Tunneled hemodialysis catheter-related bloodstream infection (CRBSI): Epidemiology, pathogenesis, clinical manifestations, and diagnosis", section on 'How to confirm diagnosis'.)

If the patient is otherwise clinically stable without evidence of a metastatic infection, then the management can be continued in the outpatient setting. In addition, unless there is evidence of an exit-site infection, stable patients can continue hemodialysis treatments using the infected dialysis catheter until a catheter exchange over a guidewire is performed. The timing of catheter exchange over a guidewire is discussed below. (See 'Definitive catheter management' below.)

Initial management in all patients — The initial management in all patients consists of collection of blood cultures, administration of antimicrobial therapy, and catheter removal or antibiotic lock therapy. In addition, patients who are hemodynamically unstable or with signs of severe sepsis should be managed with fluid resuscitation, delay of hemodialysis, and transportation to a hospital. If necessary, emergency dialysis can be performed at the hospital (algorithm 1).

Obtain blood cultures before antibiotics — Blood cultures should always be drawn among patients suspected of having a CRBSI prior to administration of antimicrobial therapy. A discussion of potential sites (ie, peripheral vein, catheter, hemodialysis circuit) of blood collection for cultures, and the criteria for diagnosis, are presented elsewhere. (See "Tunneled hemodialysis catheter-related bloodstream infection (CRBSI): Epidemiology, pathogenesis, clinical manifestations, and diagnosis", section on 'Diagnosis'.)

Blood cultures drawn prior to antimicrobial therapy are necessary to confirm presence of a CRBSI, to isolate the involved organism, and to determine sensitivities to antibiotics. Cultures can become negative quickly after initiation of antibiotics, and, therefore, have a lower sensitivity and cannot be used to exclude CRBSI. As an example, in a multicenter study of 102 patients with severe sepsis and positive blood cultures, the blood cultures became negative in 59 of these patients within a median of 70 minutes after the initial dose of intravenous antibiotics [2].

In patients who are referred to the emergency department from the outpatient dialysis unit, it is important that the emergency department or inpatient team obtain culture results collected by the outpatient unit. Blood cultures obtained in outpatient dialysis units are frequently processed at microbiology laboratories at remote sites and are not readily available to the nephrologist. For this reason, it is imperative that every dialysis unit designate a nurse to follow-up on results of blood cultures and sensitivities, and to alert the nephrologists promptly as these reports become available. Such a collaborative team model may decrease treatment failures, metastatic complications, and deaths in hemodialysis patients with CRBSIs [3].

Determine need for immediate catheter removal — Immediate removal of the infected tunneled catheter is the best catheter management method for achieving cure of CRBSI. However, this approach may result in subsequent problems in the delivery of hemodialysis, and is, therefore, reserved for specific circumstances (algorithm 1) [4,5].

After removal of the infected tunneled catheter, placement of a temporary, nontunneled catheter is typically the best alternative option for short-term hemodialysis access. A new, tunneled hemodialysis catheter can be inserted once the patient has clinically improved and has been on antimicrobial therapy for a minimum of 48 hours. However, a new tunneled catheter should not be placed until after blood cultures are negative in patients with CRBSI due to Staphylococcus aureus and Candida, and preferably (when feasible) for infections with other organisms.

Reasons for immediate catheter removal

Persistent hemodynamic instability or severe sepsis — Patients who have signs of severe sepsis or persistent hemodynamic instability despite fluid resuscitation and systemic antimicrobial therapy should have their catheter removed for source control.

Additional management of suspected sepsis and septic shock is discussed at length elsewhere. (See "Evaluation and management of suspected sepsis and septic shock in adults", section on 'Initial resuscitative therapy'.)

Metastatic infection — If a metastatic infection has already occurred, there is a concern that catheter retention will allow for additional metastatic infections to other sites. For this reason, the catheter should be removed promptly.

Exit-site infection — An exit-site infection cannot be resolved with systemic antibiotics [6]. For this reason, the dialysis catheter should be removed promptly and the subsequent catheter placed using a different site for the subcutaneous tunnel. Such patients can often have their tunneled catheter removed and undergo simultaneous placement of a tunneled catheter at an alternative site, provided that the repeat blood cultures are negative [7].

If not feasible to immediately remove the catheter

If emergency dialysis is required — Patients, once in the emergency department or those who are already admitted to the hospital, should be evaluated to determine if they need emergency dialysis (eg, pulmonary edema or severe hyperkalemia refractory to medical therapy). Patients who have persistent hemodynamic instability, severe sepsis, or metastatic infection, and who also require emergency dialysis, may be dialyzed once using the infected tunneled catheter. After dialysis is complete, the infected tunneled hemodialysis catheter should be removed promptly.

Patients with no alternative access options — In the rare case of a patient with CRBSI who has no alternative sites for placing another dialysis catheter, such that there is a concern about not being able to provide future dialysis, we continue systemic antibiotics and an antibiotic lock indefinitely without catheter removal.

Administer empiric antimicrobial therapy — We empirically treat hemodialysis patients suspected of having a CRBSI, after collection of blood cultures, with intravenous vancomycin and ceftazidime (table 1). We administer an initial vancomycin dose of 20 mg/kg and an initial ceftazidime dose of 1 gm. Some experts suggest giving a higher initial vancomycin dose (35 mg/kg) [8]; however, that approach is based upon theoretical calculations rather than clinical studies of hemodialysis patients.

In patients who are stable enough to receive hemodialysis, we administer vancomycin during the last 60 minutes of the hemodialysis session and ceftazidime immediately after completing the dialysis session. In patients who are too hemodynamically unstable for hemodialysis, the antibiotics should be administered immediately after collection of blood cultures, without waiting for a dialysis session.

For patients with a documented vancomycin allergy or documented history of vancomycin-resistant enterococci, we use intravenous daptomycin instead of vancomycin. The typical dose of daptomycin is 9 mg/kg among patients receiving hemodialysis with a high-flux dialyzer and 7 mg/kg among patients receiving hemodialysis with a low-flux dialyzer. This dose is administered during the last hour of dialysis and ensures adequate therapeutic plasma concentrations to minimize treatment failures [9].

If ceftazidime is not available, or if the patient has a severe allergy to cephalosporins, then we use aminoglycosides, such as gentamicin or tobramycin. In addition, centers with a high rate of cephalosporin resistance may also use gentamicin or tobramycin for empiric therapy. For gentamicin, the typical dose is 1 to 2 mg/kg of ideal body weight, with care not to exceed 100 mg in a single dose [10]. Gentamicin or tobramycin are typically administered in the last hour of dialysis.

We continue empiric antimicrobial therapy three times per week in conjunction with each hemodialysis session until the organism is isolated and sensitivities become available (at which time antibiotic therapy should be modified accordingly). (See 'Tailor antibiotic therapy' below.)

Subsequent doses (after the first dose) of ceftazidime and daptomycin are the same as the initial dose. However, subsequent vancomycin doses are typically lower (1 g) [11,12]. This maintenance dose of vancomycin achieves therapeutic plasma concentrations in most patients using a high-flux dialyzer, the predominant type used in the United States [12]. A lower maintenance vancomycin dose of 500 mg is sufficient among those dialyzed on a low-flux dialyzer, which removes minimal vancomycin [12]. Other experts suggest a weight-based strategy for subsequent vancomycin doses (10 to 15 mg/kg if using a high-flux dialyzer or 7.5 to 10 mg/kg if using a low-flux dialyzer) [8]; however, such an approach is based upon theoretic calculations rather than clinical data. The preceding doses are usually rounded to the nearest 250 mg increment.

Alternatively, vancomycin predialysis trough levels may be used among hospitalized patients to guide its dosing, but such facility is rarely available in the outpatient setting. Subsequent doses of gentamicin or tobramycin should be tailored to drug levels, when feasible. (See "Dosing and administration of parenteral aminoglycosides", section on 'Monitoring for toxicity' and 'Antibiotic levels' below and "Dosing and administration of parenteral aminoglycosides", section on 'Drug concentration monitoring'.)

Our choice of empiric treatment of CRBSIs (vancomycin and either ceftazidime, gentamicin, or tobramycin) aims to provide broad-spectrum coverage of common organisms involved in these infections and to permit ease of administration among patients on hemodialysis. Penicillins are rarely used in dialysis patients due to their substantial extrarenal clearance, leading to difficulty maintaining therapeutic serum levels between dialysis sessions.

Both ceftazidime and aminoglycosides provide similar empiric broad-spectrum gram-negative coverage and have pharmacokinetic properties amenable to three times weekly administration with hemodialysis. However, aminoglycoside administration in dialysis patients is associated with sustained high peak levels during the intra-dialytic period, leading to frequent occurrence of aminoglycoside ototoxicity (up to 20 percent), which is often permanent [13]. In addition, the combination of vancomycin and gentamicin or tobramycin is associated with a greater risk of ototoxicity, as compared with when each agent is administered separately. For this reason, some experts prefer ceftazidime over gentamicin or tobramycin as empiric antibiotic therapy for CRBSI [10]. Other experts prefer empiric gentamicin or tobramycin at institutions that have a high prevalence of cephalosporin resistance, with a plan to switch to less toxic antibiotics once cultures and sensitivities become available. Additional details regarding use of aminoglycosides are discussed at length elsewhere. (See "Dosing and administration of parenteral aminoglycosides" and "Pathogenesis and prevention of aminoglycoside nephrotoxicity and ototoxicity".)

Administer antibiotic lock therapy — Antibiotic lock solutions consist of a combination of antibiotics (the same as those administered systemically) and heparin (table 2). Antibiotic lock solutions are designed to kill bacteria present in biofilms that are adherent to the catheter lumens, thereby potentially eliminating the source of bacteremia without catheter removal. The antibiotic lock is administered along with systemic antibiotic therapy until the catheter is replaced. While we prefer to administer antibiotic locks in conjunction with systemic antimicrobial therapy, some dialysis units may lack the capability of administering antibiotic locks. In such cases, systemic antimicrobial therapy alone can be continued until the catheter is replaced.

The contents of the antibiotic lock are changed to match any changes made to the systemic antibiotic regimen (eg, if the culture results indicate growth of gram-positive cocci and the systemic antibiotic regimen is changed to discontinue ceftazidime, then the antibiotic lock should be changed to vancomycin and heparin only, without ceftazidime). We only administer antibiotic locks for vancomycin, ceftazidime, and cefazolin. Antibiotics other than these are not usually part of antibiotic locks at our center.

Antibiotic lock therapy is not necessary among patients who have indications for immediate catheter removal. (See 'Determine need for immediate catheter removal' above.)

Lock solutions are prepared by mixing aliquots of stock solutions in a single syringe, and then instilling this mixed syringe solution into each catheter lumen after completion of a hemodialysis session [10] (table 2):

The stock solutions for antibiotic lock are as follows:

Vancomycin 1 g in 100 mL of normal saline

Ceftazidime 1 g in 50 mL of normal saline

Cefazolin 2 g in 100 mL of normal saline

Heparin 1000 units/mL

In the rare situations where the volume of the catheter lumen is greater than 2 mL, the difference in volume should be made up with additional heparin. The antibiotic lock is renewed after every hemodialysis session. Heparin locks are resumed once the course of intravenous antibiotics has been completed.

If a patient has heparin-induced thrombocytopenia (HIT), the heparin in the antibiotic lock is substituted with normal saline.

Antibiotic lock solutions should be prepared by pharmacists immediately before instillation into the catheter lumen. However, pharmacists are not usually available to mix lock solutions in outpatient settings, such as in community-based free-standing dialysis units. In such settings, nurses should be trained, according to a written protocol, to prepare these solutions and to use safe injection practices.  

There are no prospective studies comparing the efficacy of antibiotic lock therapy versus prompt exchange of the catheter over a guidewire as initial therapy. Data supporting the efficacy of antibiotic lock solutions in concert with systemic antibiotics come from case series [14-22]. In these series, the success rates of antibiotic locks in curing CRBSI were highly dependent upon the infecting organism. As an example, the success rate was approximately 90 to 100 percent with gram-negative infections, approximately 80 percent with Staphylococcus epidermidis coagulase-negative staphylococcal infections, approximately 60 percent with Enterococcus infections, and approximately 40 percent with S. aureus infections [14,16,19,23,24]. Due to the low success rate with S. aureus infections, many experts proceed with removal of the catheter in patients with CRBSI due to this organism, rather than attempting catheter salvage with an antibiotic lock. On the other hand, in patients with gram-negative or S. epidermidis CRBSI, the use of antibiotic lock therapy frequently allows for continuation of hemodialysis through the infected tunneled catheter without catheter exchange, thereby limiting the number of procedures for the patient. (See 'Initial management in all patients' above and 'Definitive catheter management' below.)

Subsequent management in all patients — The initial management of CRBSI as described above is continued until a pathogen is identified or until the initial preantibiotic cultures return negative (algorithm 1). (See 'Initial management in all patients' above.)

Upon identification of the pathogen, subsequent management consists of tailored antimicrobial therapy and definitive catheter management. (See 'Tailor antibiotic therapy' below and 'Definitive catheter management' below.)

Tailor antibiotic therapy — Once the organism and antibiotic sensitivities have been identified, the antibiotic regimen should be modified accordingly. As with empiric antimicrobials, an important factor in choosing an antibiotic is the ease of administration with each hemodialysis session. As noted above, it is important that clinicians who continue to manage the patient in the hospital setting follow up on blood cultures collected prior to antibiotic therapy. (See 'Obtain blood cultures before antibiotics' above.)

The changes in the antimicrobial therapy should be made both to the systemically administered doses and to those included in the antibiotic lock. As discussed above, we do not continue antibiotic lock therapy for S. aureus infections, and replace the catheter instead. (See 'Administer antibiotic lock therapy' above and 'Definitive catheter management' below.)

We generally treat with antibiotics (ie, the initial empiric antibiotics and the tailored antibiotic) for a total duration of three weeks, with the exception of S. aureus infections, which we treat for four weeks. The duration of treatment is often longer if the CRBSI is complicated by a metastatic infection. (See 'Management of metastatic infections' below.)

In addition, we request consultation with infectious disease specialists when the isolated pathogen is either S. aureus or Candida species. Infectious disease consultation can improve clinical outcomes in such patients [25].

Among patients with a methicillin-resistant S. aureus infection, we continue to administer vancomycin. We continue daptomycin among those who are allergic to vancomycin. Dosing of these antibiotics is the same as used for empiric therapy after the initial loading dose. (See 'Administer empiric antimicrobial therapy' above.)

Among patients with a methicillin-sensitive staphylococcus (MSSA) infection, we change the antibiotic to intravenous cefazolin at a dose of 2 g after each hemodialysis session [26].  

Our preference for cefazolin in this setting is due, in part, to the observation that the widespread use of vancomycin has been associated with an increasing incidence of infections with vancomycin-resistant enterococci [27]. In addition, cefazolin is more effective than vancomycin for treatment of MSSA infections [26,28-30].

Among patients allergic to cephalosporins, we continue intravenous vancomycin.

Among patients with a vancomycin-resistant Enterococcus infection, we treat with intravenous daptomycin [9]. Dosing of daptomycin is similar to that used for empiric therapy. (See 'Administer empiric antimicrobial therapy' above.)

Among patients with gram-negative infections that are sensitive to ceftazidime, we continue ceftazidime rather than changing to a different antibiotic. This choice is based upon ease of administration with hemodialysis and widespread availability of ceftazidime in most outpatient dialysis units in the United States. The dosing of ceftazidime is presented above. (See 'Administer empiric antimicrobial therapy' above.)

In many institutions, most of the gram-negative bacteria isolated in hemodialysis CRBSI remain sensitive to both aminoglycosides and third generation cephalosporins [14,15], but in regions or institutions in which resistance to ceftazidime is more common, or in situations with severe cephalosporin allergy (eg, anaphylaxis), aminoglycosides or drugs such as aztreonam may be alternate choices. Aztreonam is preferred, especially with enterobacteriaceae, rather than aminoglycosides due to its superior safety profile. Aztreonam should not be used to treat pseudomonas infections. When feasible, consultation with an infectious disease specialist is advised for infections due to Pseudomonas aeruginosa and other gram-negative pathogens with difficult-to-treat resistance profiles, such as carbapenem-resistant and extended-spectrum beta-lactamase-producing Enterobacterales [31]. (See "Principles of antimicrobial therapy of Pseudomonas aeruginosa infections".)    

Among patients with a Candida infection, optimal therapy depends upon the species of Candida recovered, the immune status of the patient, the local prevalence of resistance to antifungal agents, and the availability of susceptibility testing to antifungal agents. Management should also include careful assessment and follow-up for metastatic infection and treatment failure or relapse. (See "Management of candidemia and invasive candidiasis in adults".)

Empiric antimicrobial therapy can be stopped among patients who have negative results on both sets of initial blood cultures drawn before administration of antibiotics (the diagnosis of CRBSI is excluded in such patients), unless antibiotics are being continued to treat an alternative source of infection [4].

Definitive catheter management — Most patients will respond to intravenous antimicrobial therapy when administered concurrently with antibiotic lock therapy, will have clearance of bacteremia, and will not require immediate catheter removal [32]. In general, such patients can have their catheter exchanged over a guidewire once they have notable clinical improvement after 48 hours of appropriate antibiotic therapy (algorithm 1).

In addition to patients who need immediate catheter removal (see 'Determine need for immediate catheter removal' above), we proceed with catheter removal, rather than replacement over a guidewire, among the following patients:

Patients who have a persistent fever and/or bacteremia 48 to 72 hours after initiation of antibiotics to which the organism is susceptible

When infection is due to difficult-to-cure pathogens, such as S. aureus, pseudomonas, Candida, other fungi, or multiply-resistant bacterial pathogens (see "Management of candidemia and invasive candidiasis in adults")

A new tunneled catheter should not be placed until after blood cultures are negative in patients with CRBSI due to S. aureus and Candida, and preferably (when feasible) for infections with other organisms.

Leaving the infected catheter in place is not recommended in CRBSI due to S. aureus, Candida, other fungi, or multiply-resistant bacterial pathogens. Intravenous antibiotics alone (without removal of the infected catheter) are usually insufficient to eradicate CRBSI caused by these organisms. Although patients with established biofilms on the surface or the lumens of infected catheters may transiently appear to respond to such intravenous antimicrobial therapy, bacteremia often recurs when such therapy is discontinued. Large observational studies found that a clinical cure occurred in less than 40 percent of patients whose CRBSI was treated with systemic antibiotics alone (without catheter replacement or antibiotic lock) [7,33,34]. Conversely, in some studies, the use of antibiotic lock therapy with delayed catheter exchange was as effective as immediate catheter removal [32].

Thus, if the symptoms that prompted initiation of treatment resolve within 48 to 72 hours after initiation of systemic antibiotics, the infected catheter can be exchanged with a new catheter over a guidewire. We base this decision for catheter exchange on symptoms rather than blood culture results, especially among outpatients, due to the nature of reporting of laboratory results in the outpatient hemodialysis setting. The blood cultures collected at outpatient hemodialysis units are shipped to a commercial laboratory in a distant location rather than a local laboratory, adding significant delays to their availability. Thus, we perform a catheter exchange over a guidewire in asymptomatic patients prior to confirming that bacteremia has resolved. However, we always check follow-up blood cultures 24 to 48 hours after such guidewire-assisted catheter exchanges to verify that the bacteremia has indeed resolved, even if the patient remains asymptomatic. This is because bacteremia can be present in patients lacking signs and/or symptoms of an ongoing bloodstream infection. If these surveillance blood cultures return positive, then the tunneled catheter should be removed as cure of infection is unlikely in the face of a documented ongoing bacteremia.

In the rare instances of patients with no other dialysis access, we continue systemic antibiotics and antibiotic locks indefinitely.

Management of metastatic infections — A metastatic infection can be a life-threatening complication of CRBSIs, especially with S. aureus bacteremia. (See "Clinical manifestations of Staphylococcus aureus infection in adults", section on 'Bacteremia'.)

We obtain infectious disease consultation among all patients with CRBSIs who have a metastatic infection. Evaluation and management of individual metastatic complications are discussed at length elsewhere:

Endocarditis (see "Overview of management of infective endocarditis in adults" and "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis", section on 'Evaluation' and "Right-sided native valve infective endocarditis", section on 'Diagnosis')

Osteomyelitis (see "Nonvertebral osteomyelitis in adults: Clinical manifestations and diagnosis", section on 'Hematogenous osteomyelitis' and "Nonvertebral osteomyelitis in adults: Treatment", section on 'Hematogenous osteomyelitis' and "Nonvertebral osteomyelitis in adults: Treatment", section on 'Antibiotic therapy')

Brain abscess (see "Pathogenesis, clinical manifestations, and diagnosis of brain abscess", section on 'Hematogenous spread' and "Pathogenesis, clinical manifestations, and diagnosis of brain abscess", section on 'Evaluation and diagnosis' and "Treatment and prognosis of bacterial brain abscess", section on 'Abscess from hematogenous spread')

Monitoring on antimicrobial therapy

Repeat blood cultures — We check follow-up blood cultures in all patients with S. aureus bacteremia, bacteremia due to Pseudomonas aeruginosa, and Candidemia, regardless of their clinical status. In other situations, follow-up blood cultures are optional depending upon the clinical setting (ie, inpatient versus outpatient) and whether an alternate source for the bacteremia is deemed possible.

We also check blood cultures one week after completion of antibiotic therapy among all patients with CRBSI, whether or not the initial catheter was removed. We also check serial blood cultures during antibiotic treatment among patients who have S. aureus bacteremia until the resolution of bacteremia is confirmed, and among patients who have signs or symptoms consistent with ongoing infection.

Antibiotic levels — Serum antibiotic levels for vancomycin and aminoglycosides are frequently measured in the hospital setting to ensure therapeutic serum levels. By contrast, antibiotic levels are rarely obtained among dialysis outpatients due to the logistic difficulties and use of remote laboratories. The doses we describe above typically achieve therapeutic levels in hemodialysis patients.

The frequency of aminoglycoside ototoxicity may be quite high (up to 20 percent) and, in addition, may be permanent [13]. Thus, if, after culture results and sensitivities are obtained, therapy with an aminoglycoside is selected for definitive treatment, then we obtain drug levels predialysis until the administered dose amount is constant. However, this may not be feasible in some dialysis units, making aminoglycosides an undesirable choice that should be used only when necessary. This issue and target therapeutic levels are discussed separately. (See "Dosing and administration of parenteral aminoglycosides".)

Catheter management for nontunneled hemodialysis catheters — Any patient with a temporary nontunneled hemodialysis catheter who has a suspected CRBSI should have their catheters removed immediately upon confirmation of bacteremia, similar to patients with other types of nontunneled central venous catheters.

PREVENTION — With nonhemodialysis intravascular catheters, a number of measures can be used to help prevent catheter-related infections. Although most of the approaches apply to hemodialysis catheters, some cannot be used in the hemodialysis setting. (See "Routine care and maintenance of intravenous devices" and "Central venous catheters for acute and chronic hemodialysis access and their management", section on 'Routine care and access for hemodialysis'.)

Methods we use — Our strategy to prevent dialysis CRBSI includes general preventive measures and the use of chlorhexidine-coated catheter hub devices. In select patients, the use of taurolidine catheter locking solutions is a reasonable alternative to chlorhexidine-coated catheter caps. Our approach is detailed below:

General preventive measures – General measures to reduce catheter-related infections include the following:

Hemodialysis units should develop a written protocol describing in detail the proper use of the aseptic technique when vascular access catheters are manipulated and when dressings are applied after hemodialysis sessions.

All personnel should be adequately trained in aseptic techniques and educated about the importance of routine hand hygiene before and after patient contact. Hand hygiene is necessary before and after gloves are donned to prevent cross-contamination.

The patient should wear a mask during access and disconnection of the catheter from the hemodialysis tubing.

A chlorhexidine gluconate-impregnated sponge should be used in hemodialysis catheter dressings.

Chlorhexidine-coated catheter caps – In patients with tunneled hemodialysis catheters, we suggest the use of chlorhexidine-coated catheter caps in addition to general preventive measures, rather than general preventive measures alone. Disposable, single-use catheter caps that contain a chlorhexidine-coated rod extending into the catheter lumen (eg, ClearGuard HD caps) reduce the risk of dialysis CRBSI and are commonly used in the United States and other resource-abundant settings. Chlorhexidine-coated catheter caps may be used with heparin, citrate, and saline catheter lock solutions.

Findings from two cluster-randomized, open-label trials as well as observational data support the use of chlorhexidine-coated catheter caps to prevent dialysis catheter-related infections [35-38]. In the largest trial, in which over 2400 patients undergoing maintenance hemodialysis via a central venous catheter were randomly assigned to chlorhexidine-coated catheter caps or to standard caps for 12 months, 46 positive blood culture episodes occurred in the chlorhexidine cap group compared with 107 in the standard cap group (incidence rate ratio [IRR] 0.44, 95% CI 0.23-0.83) [35]. In addition, the rate of hospital admission for bloodstream infections was 40 percent less in the chlorhexidine cap group (IRR 0.60, 95% CI 0.37-0.97). No device-related adverse events were reported.

Taurolidine catheter locks in select patients – The use of taurolidine-containing catheter lock solutions rather than chlorhexidine-coated catheter caps (as described above) is reasonable in the following scenarios:

In settings where chlorhexidine-coated caps are unavailable

In dialysis facilities with high rates of CRBSI (eg, >3.5 per 1000 catheter days) despite the use of chlorhexidine-coated caps

In patients with a previous episode of tunneled hemodialysis CRBSI despite the use of chlorhexidine-coated caps

Taurolidine is an antimicrobial agent with a favorable resistance profile [39,40] and is considered safe for use in heparin and citrate lock solutions [41]. Because there are no data demonstrating compatibility between taurolidine and chlorhexidine, taurolidine-containing lock solutions should not yet be used in conjunction with chlorhexidine-coated catheter caps. A taurolidine and heparin dialysis catheter lock solution received regulatory approval in the United States in November 2023 [42].

The best evidence to support the use of a taurolidine-containing lock solution in the dialysis setting comes from a trial in which nearly 800 patients undergoing maintenance hemodialysis via a central venous catheter were randomly assigned to a taurolidine and heparin catheter lock or to a heparin control catheter lock for a mean follow-up of 200 days [43]. No patients in either group used chlorhexidine-coated catheter caps. Nine patients (2 percent) in the taurolidine group and 32 patients (8 percent) in the control group developed a CRBSI (hazard ratio [HR] 0.29, 95% CI 0.14-0.62) and adverse events were similar in both groups. Previous small trials and observational data also support the use of taurolidine-containing catheter locks to reduce hemodialysis CRBSI [44-47].

In addition to the methods above, we monitor rates of hemodialysis-associated infections to detect and understand local trends in types of pathogens, incidence, and antimicrobial resistance in a manner similar to that described by others [48].

Methods we do not use — Multiple groups have tried to further decrease the risk of catheter infection in hemodialysis patients by using various other methods. These principally involve variations in exit-site care (including antimicrobial application to the exit site) [49-52], attempts at elimination of S. aureus nasal carriage [53], the use of different types of hemodialysis catheters, and the topical application of different substances. However, we do not use any of these techniques at our dialysis units.

In addition, we do not use antibiotic locks [54-56], antimicrobial locks with ethanol or citrate [57], or catheters impregnated with antimicrobial agents [58-60] in our hemodialysis units for prevention of hemodialysis CRBSI.

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Dialysis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

Beyond the Basics topics (see "Patient education: Dialysis or kidney transplantation — which is right for me? (Beyond the Basics)" and "Patient education: Hemodialysis (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

Tunneled catheters are used for short- and intermediate-term venous access among hemodialysis patients. Tunneled catheters are associated with a number of complications, in particular catheter-related bloodstream infection (CRBSI). (See 'Introduction' above.)  

Triage of outpatients – We transfer the following outpatients to the emergency department (algorithm 1) (see 'Triage in the outpatient dialysis unit' above):

Patients who are hemodynamically unstable or have signs of severe sepsis  

Patients who have symptoms or signs of a metastatic infection

Patients who have clear evidence of an exit-site infection (eg, pus at the exit site)  

Such patients should have their blood cultures drawn, any purulent exit-site drainage sent for culture, and empiric broad-spectrum antimicrobial therapy initiated prior to their departure from the outpatient dialysis unit.

Patients who do not require transfer to the emergency department can have hemodialysis treatments using the infected dialysis catheter until a catheter exchange over a guidewire is performed.

Initial management after triage (algorithm 1):

Blood cultures should always be drawn among patients suspected of having CRBSI prior to administration of antimicrobial therapy. A discussion of potential sites (ie, peripheral vein, catheter, hemodialysis circuit) of blood collection for cultures, and the criteria for diagnosis, are presented elsewhere. (See "Tunneled hemodialysis catheter-related bloodstream infection (CRBSI): Epidemiology, pathogenesis, clinical manifestations, and diagnosis", section on 'Diagnosis' and 'Obtain blood cultures before antibiotics' above.)

We suggest immediate removal of the infected catheter, rather than salvage or a delayed exchange over a guidewire, among patients with persistent hemodynamic instability or severe sepsis despite fluid resuscitation and systemic antimicrobial therapy; presence of a metastatic infection; or presence of an exit-site infection (Grade 2C). However, in such patients, catheter removal can be delayed for those who require emergency dialysis or deferred in those who have no other access options. (See 'Determine need for immediate catheter removal' above.)

-Our empiric antimicrobial therapy usually consists of intravenous vancomycin at 20 mg/kg and ceftazidime 1 g. Dosing and additional details (including alternative antimicrobial agents) are discussed above (table 1). (See 'Administer empiric antimicrobial therapy' above.)

-With the exception of patients who require immediate catheter removal, we suggest administration of antibiotic lock therapy in addition to systemic antimicrobial therapy rather than systemic antimicrobial therapy alone among patients with hemodialysis CRBSI (Grade 2C). Antibiotic lock consists of a combination of antibiotics (the same as those administered systemically) and heparin. Dosing and administration of antibiotic lock therapy is discussed in detail above (table 2). (See 'Administer antibiotic lock therapy' above.)

Subsequent management (algorithm 1):

Once the organism and antibiotic sensitivities have been identified, the antibiotic regimen should be tailored accordingly based on culture results. (See 'Tailor antibiotic therapy' above.)

Most patients will respond to intravenous antimicrobial therapy when administered concurrently with antibiotic lock therapy, will have clearance of bacteremia, and will not require catheter removal. In general, such patients can have their catheter exchanged over a guidewire once they have notable clinical improvement after 48 hours of appropriate antibiotic therapy.

We suggest catheter removal, rather than replacement over a guidewire, among patients who have a persistent fever and/or bacteremia 48 to 72 hours after initiation of antibiotics to which the organism is susceptible and patients with difficult-to-cure pathogens, such as S. aureus, pseudomonas, Candida, other fungi, or multiply-resistant bacterial pathogens (Grade 2C).

A new tunneled catheter should not be placed until after blood cultures are negative in patients with CRBSI due to S. aureus and Candida, and preferably (when feasible) for infections with other organisms. (See 'Definitive catheter management' above.)

Management of metastatic infections – A metastatic infection can be a life-threatening complication of CRBSIs, especially with S. aureus bacteremia. We obtain infectious disease consultation among all patients with CRBSIs who have a metastatic infection. (See "Clinical manifestations of Staphylococcus aureus infection in adults", section on 'Bacteremia' and 'Management of metastatic infections' above.)

Monitoring – We check blood cultures one week after completion of antibiotic therapy among all patients with CRBSI, whether or not the initial catheter was removed. We also check serial blood cultures during antibiotic treatment among patients who have S. aureus bacteremia until the resolution of bacteremia is confirmed, and among patients who have signs or symptoms consistent with ongoing infection.

Serum antibiotic levels for vancomycin and aminoglycosides are frequently measured in the hospital setting to ensure therapeutic serum levels. By contrast, antibiotic levels are rarely obtained among dialysis outpatients due to the logistic difficulties and use of remote laboratories. If, after culture results and sensitivities are obtained, therapy with gentamicin or tobramycin is selected for definitive treatment, then we obtain drug levels predialysis until the administered dose amount is constant. (See 'Monitoring on antimicrobial therapy' above.)

Prevention – An important component of preventing dialysis CRBSI is the use of general measures to ensure aseptic technique when catheters are manipulated and dressed. In patients with tunneled hemodialysis catheters, we suggest the use of chlorhexidine-coated catheter caps in addition to general preventive measures, rather than general preventive measures alone (Grade 2C). Taurolidine-containing catheter lock solutions rather than chlorhexidine-coated catheter caps are reasonable in select patients. (See 'Prevention' above.)

  1. Hemodialysis Adequacy 2006 Work Group. Clinical practice guidelines for hemodialysis adequacy, update 2006. Am J Kidney Dis 2006; 48 Suppl 1:S2.
  2. Cheng MP, Stenstrom R, Paquette K, et al. Blood Culture Results Before and After Antimicrobial Administration in Patients With Severe Manifestations of Sepsis: A Diagnostic Study. Ann Intern Med 2019; 171:547.
  3. Mokrzycki MH, Zhang M, Golestaneh L, et al. An interventional controlled trial comparing 2 management models for the treatment of tunneled cuffed catheter bacteremia: a collaborative team model versus usual physician-managed care. Am J Kidney Dis 2006; 48:587.
  4. Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 Update by the Infectious Diseases Society of America. Clin Infect Dis 2009; 49:1.
  5. Rijnders BJ, Peetermans WE, Verwaest C, et al. Watchful waiting versus immediate catheter removal in ICU patients with suspected catheter-related infection: a randomized trial. Intensive Care Med 2004; 30:1073.
  6. Sychev D, Maya ID, Allon M. Clinical management of dialysis catheter-related bacteremia with concurrent exit-site infection. Semin Dial 2011; 24:239.
  7. Beathard GA. Management of bacteremia associated with tunneled-cuffed hemodialysis catheters. J Am Soc Nephrol 1999; 10:1045.
  8. Rybak MJ, Le J, Lodise TP, et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: A revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. Am J Health Syst Pharm 2020; 77:835.
  9. Salama NN, Segal JH, Churchwell MD, et al. Intradialytic administration of daptomycin in end stage renal disease patients on hemodialysis. Clin J Am Soc Nephrol 2009; 4:1190.
  10. Allon M. Treatment guidelines for dialysis catheter-related bacteremia: an update. Am J Kidney Dis 2009; 54:13.
  11. Barth RH, DeVincenzo N. Use of vancomycin in high-flux hemodialysis: experience with 130 courses of therapy. Kidney Int 1996; 50:929.
  12. Taylor ME, Allon M. Practical vancomycin dosing in hemodialysis patients in the era of emerging vancomycin resistance: a single-center experience. Am J Kidney Dis 2010; 55:1163.
  13. Feldman L, Efrati S, Eviatar E, et al. Gentamicin-induced ototoxicity in hemodialysis patients is ameliorated by N-acetylcysteine. Kidney Int 2007; 72:359.
  14. Poole CV, Carlton D, Bimbo L, Allon M. Treatment of catheter-related bacteraemia with an antibiotic lock protocol: effect of bacterial pathogen. Nephrol Dial Transplant 2004; 19:1237.
  15. Krishnasami Z, Carlton D, Bimbo L, et al. Management of hemodialysis catheter-related bacteremia with an adjunctive antibiotic lock solution. Kidney Int 2002; 61:1136.
  16. Vardhan A, Davies J, Daryanani I, et al. Treatment of haemodialysis catheter-related infections. Nephrol Dial Transplant 2002; 17:1149.
  17. Capdevila JA, Segarra A, Planes AM, et al. Successful treatment of haemodialysis catheter-related sepsis without catheter removal. Nephrol Dial Transplant 1993; 8:231.
  18. Boorgu R, Dubrow AJ, Levin NW, et al. Adjunctive antibiotic/anticoagulant lock therapy in the treatment of bacteremia associated with the use of a subcutaneously implanted hemodialysis access device. ASAIO J 2000; 46:767.
  19. Fernandez-Hidalgo N, Almirante B, Calleja R, et al. Antibiotic-lock therapy for long-term intravascular catheter-related bacteraemia: results of an open, non-comparative study. J Antimicrob Chemother 2006; 57:1172.
  20. Messing B, Peitra-Cohen S, Debure A, et al. Antibiotic-lock technique: a new approach to optimal therapy for catheter-related sepsis in home-parenteral nutrition patients. JPEN J Parenter Enteral Nutr 1988; 12:185.
  21. Panagea S, Galloway A. Intravascular-catheter-related infections. Lancet 1998; 351:1738.
  22. Atkinson JB, Chamberlin K, Boody BA. A prospective randomized trial of urokinase as an adjuvant in the treatment of proven Hickman catheter sepsis. J Pediatr Surg 1998; 33:714.
  23. Maya ID, Carlton D, Estrada E, Allon M. Treatment of dialysis catheter-related Staphylococcus aureus bacteremia with an antibiotic lock: a quality improvement report. Am J Kidney Dis 2007; 50:289.
  24. Peterson WJ, Maya ID, Carlton D, et al. Treatment of dialysis catheter-related Enterococcus bacteremia with an antibiotic lock: a quality improvement report. Am J Kidney Dis 2009; 53:107.
  25. Lee RA, Zurko JC, Camins BC, et al. Impact of Infectious Disease Consultation on Clinical Management and Mortality in Patients With Candidemia. Clin Infect Dis 2019; 68:1585.
  26. Stryjewski ME, Szczech LA, Benjamin DK Jr, et al. Use of vancomycin or first-generation cephalosporins for the treatment of hemodialysis-dependent patients with methicillin-susceptible Staphylococcus aureus bacteremia. Clin Infect Dis 2007; 44:190.
  27. Tokars JI. Vancomycin use and antimicrobial resistance in hemodialysis centers. Am J Kidney Dis 1998; 32:521.
  28. Marx MA, Frye RF, Matzke GR, Golper TA. Cefazolin as empiric therapy in hemodialysis-related infections: efficacy and blood concentrations. Am J Kidney Dis 1998; 32:410.
  29. Fogel MA, Nussbaum PB, Feintzeig ID, et al. Cefazolin in chronic hemodialysis patients: a safe, effective alternative to vancomycin. Am J Kidney Dis 1998; 32:401.
  30. Chan KE, Warren HS, Thadhani RI, et al. Prevalence and outcomes of antimicrobial treatment for Staphylococcus aureus bacteremia in outpatients with ESRD. J Am Soc Nephrol 2012; 23:1551.
  31. Tamma PD, Aitken SL, Bonomo RA, et al. Infectious Diseases Society of America Guidance on the Treatment of Antimicrobial Resistant Gram-Negative Infections. (Available online at: https://www.idsociety.org/practice-guideline/amr-guidance. Accessed on October 12, 2020.).
  32. Aslam S, Vaida F, Ritter M, Mehta RL. Systematic review and meta-analysis on management of hemodialysis catheter-related bacteremia. J Am Soc Nephrol 2014; 25:2927.
  33. Marr KA, Sexton DJ, Conlon PJ, et al. Catheter-related bacteremia and outcome of attempted catheter salvage in patients undergoing hemodialysis. Ann Intern Med 1997; 127:275.
  34. Saad TF. Bacteremia associated with tunneled, cuffed hemodialysis catheters. Am J Kidney Dis 1999; 34:1114.
  35. Hymes JL, Mooney A, Van Zandt C, et al. Dialysis Catheter-Related Bloodstream Infections: A Cluster-Randomized Trial of the ClearGuard HD Antimicrobial Barrier Cap. Am J Kidney Dis 2017; 69:220.
  36. Brunelli SM, Van Wyck DB, Njord L, et al. Cluster-Randomized Trial of Devices to Prevent Catheter-Related Bloodstream Infection. J Am Soc Nephrol 2018; 29:1336.
  37. Weiss S, Qureshi M. Evaluating a Novel Hemodialysis Central Venous Catheter Cap in Reducing Bloodstream Infections: A Quality Improvement Initiative. Int J Nephrol Renovasc Dis 2021; 14:125.
  38. Johansen KL, Gilbertson DT, Wetmore JB, et al. Catheter-Associated Bloodstream Infections among Patients on Hemodialysis: Progress before and during the COVID-19 Pandemic. Clin J Am Soc Nephrol 2022; 17:429.
  39. Pittiruti M, Bertoglio S, Scoppettuolo G, et al. Evidence-based criteria for the choice and the clinical use of the most appropriate lock solutions for central venous catheters (excluding dialysis catheters): a GAVeCeLT consensus. J Vasc Access 2016; 17:453.
  40. Olthof ED, Rentenaar RJ, Rijs AJ, Wanten GJ. Absence of microbial adaptation to taurolidine in patients on home parenteral nutrition who develop catheter related bloodstream infections and use taurolidine locks. Clin Nutr 2013; 32:538.
  41. van den Bosch CH, Jeremiasse B, van der Bruggen JT, et al. The efficacy of taurolidine containing lock solutions for the prevention of central-venous-catheter-related bloodstream infections: a systematic review and meta-analysis. J Hosp Infect 2022; 123:143.
  42. FDA approves new drug under special pathway for patients receiving hemodialysis. US Food and Drug administration. Available at: https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-new-drug-under-special-pathway-patients-receiving-hemodialysis (Accessed on December 01, 2023).
  43. Agarwal AK, Roy-Chaudhury P, Mounts P, et al. Taurolidine/Heparin Lock Solution and Catheter-Related Bloodstream Infection in Hemodialysis: A Randomized, Double-Blind, Active-Control, Phase 3 Study. Clin J Am Soc Nephrol 2023; 18:1446.
  44. Solomon LR, Cheesbrough JS, Bhargava R, et al. Observational study of need for thrombolytic therapy and incidence of bacteremia using taurolidine-citrate-heparin, taurolidine-citrate and heparin catheter locks in patients treated with hemodialysis. Semin Dial 2012; 25:233.
  45. Murray EC, Deighan C, Geddes C, Thomson PC. Taurolidine-citrate-heparin catheter lock solution reduces staphylococcal bacteraemia rates in haemodialysis patients. QJM 2014; 107:995.
  46. Winnicki W, Herkner H, Lorenz M, et al. Taurolidine-based catheter lock regimen significantly reduces overall costs, infection, and dysfunction rates of tunneled hemodialysis catheters. Kidney Int 2018; 93:753.
  47. Solomon LR, Cheesbrough JS, Ebah L, et al. A randomized double-blind controlled trial of taurolidine-citrate catheter locks for the prevention of bacteremia in patients treated with hemodialysis. Am J Kidney Dis 2010; 55:1060.
  48. Saad TF. Central venous dialysis catheters: catheter-associated infection. Semin Dial 2001; 14:446.
  49. James MT, Conley J, Tonelli M, et al. Meta-analysis: antibiotics for prophylaxis against hemodialysis catheter-related infections. Ann Intern Med 2008; 148:596.
  50. McCann M, Moore ZE. Interventions for preventing infectious complications in haemodialysis patients with central venous catheters. Cochrane Database Syst Rev 2010; :CD006894.
  51. Battistella M, Bhola C, Lok CE. Long-term follow-up of the Hemodialysis Infection Prevention with Polysporin Ointment (HIPPO) Study: a quality improvement report. Am J Kidney Dis 2011; 57:432.
  52. Rosenblum A, Wang W, Ball LK, et al. Hemodialysis catheter care strategies: a cluster-randomized quality improvement initiative. Am J Kidney Dis 2014; 63:259.
  53. Yu VL, Goetz A, Wagener M, et al. Staphylococcus aureus nasal carriage and infection in patients on hemodialysis. Efficacy of antibiotic prophylaxis. N Engl J Med 1986; 315:91.
  54. Jaffer Y, Selby NM, Taal MW, et al. A meta-analysis of hemodialysis catheter locking solutions in the prevention of catheter-related infection. Am J Kidney Dis 2008; 51:233.
  55. Moran J, Sun S, Khababa I, et al. A randomized trial comparing gentamicin/citrate and heparin locks for central venous catheters in maintenance hemodialysis patients. Am J Kidney Dis 2012; 59:102.
  56. Moore CL, Besarab A, Ajluni M, et al. Comparative effectiveness of two catheter locking solutions to reduce catheter-related bloodstream infection in hemodialysis patients. Clin J Am Soc Nephrol 2014; 9:1232.
  57. Weijmer MC, van den Dorpel MA, Van de Ven PJ, et al. Randomized, clinical trial comparison of trisodium citrate 30% and heparin as catheter-locking solution in hemodialysis patients. J Am Soc Nephrol 2005; 16:2769.
  58. Kamal GD, Pfaller MA, Rempe LE, Jebson PJ. Reduced intravascular catheter infection by antibiotic bonding. A prospective, randomized, controlled trial. JAMA 1991; 265:2364.
  59. Dahlberg PJ, Agger WA, Singer JR, et al. Subclavian hemodialysis catheter infections: a prospective, randomized trial of an attachable silver-impregnated cuff for prevention of catheter-related infections. Infect Control Hosp Epidemiol 1995; 16:506.
  60. Jain G, Allon M, Saddekni S, et al. Does heparin coating improve patency or reduce infection of tunneled dialysis catheters? Clin J Am Soc Nephrol 2009; 4:1787.
Topic 1966 Version 30.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟