Abstract
Background and objectives: Candidemia is a rare complication in catheter-dependent hemodialysis patients. As a result, there is uncertainty about its optimal medical management. The goal of this retrospective study was to compare the clinical outcomes of catheter-related candidemia managed with two different strategies: Guidewire exchange of the infected catheter versus removal with delayed replacement.
Design, setting, participants, & measurements: We retrospectively queried a prospective, computerized vascular access database to identify 40 hemodialysis patients with catheter-related candidemia. All patients underwent treatment with antifungal medications for 2 wk, in conjunction with guidewire catheter exchange or catheter removal with delayed replacement. The primary outcomes were major complications, recurrent candidemia, and patient survival.
Results: Candidemia represented approximately 2% of all cases of catheter-related bloodstream infections. Of the 40 patients with candidemia, 27 underwent guidewire catheter exchange and 13 had prompt catheter removal with delayed replacement. The two treatment groups were similar in demographic, clinical, and catheter characteristics. Only 1 (2.5%) patient developed a serious complication (endophthalmitis). Recurrence of candidemia within 3 mo was observed in 15% of each treatment group. Patient survival at 6 mo was similar in both groups.
Conclusions: Catheter-related candidemia is rare in hemodialysis patients and has a low complication rate. Catheter exchange over a guidewire in conjunction with antifungal therapy is an effective and safe treatment regimen.
Candidemia is a widely recognized nosocomial infection in non-neutropenic hospitalized patients with intravascular catheters (1,2). It can be complicated by osteomyelitis, septic arthritis, endocarditis, central nervous system candidiasis, and endophthalmitis (3). Systemic antifungal agents do not eradicate the Candida catheter biofilm (4), suggesting that the central vein catheter should be removed in patients with catheter-related candidemia. Several large, prospective studies observed a shorter duration of candidemia, better clinical outcomes, and lower mortality when the central vein catheter was removed or replaced (1,2,5–7). These observations form the basis of the current guidelines, which recommend removing the intravascular catheter to eradicate the source of candidemia (3).
Candidemia is a relatively uncommon complication of hemodialysis catheters; therefore, there are no large series describing its frequency, complications, or optimal medical management. Dialysis catheter–related candidemia is typically treated with an antifungal drug in conjunction with catheter removal and delayed placement of a new, tunneled dialysis catheter. This strategy creates hardship in managing the patient's dialysis, because it requires placement of a temporary dialysis catheter. In patients with dialysis catheter–related bacteremia, exchange of the infected tunneled catheter for a new one over a guidewire can achieve a high cure rate while simplifying access management (8–12). It is unknown whether this strategy is effective and safe for management of dialysis catheter–related candidemia.
The goal of this study was to evaluate the frequency and medical complications of dialysis catheter–related candidemia. In addition, we evaluated whether guidewire exchange of the infected tunneled catheter is a viable alternative to catheter removal with delayed replacement.
Materials and Methods
Diagnosis and Treatment of Candidemia
All participating patients in the study were catheter-dependent hemodialysis patients who were treated at University of Alabama at Birmingham (UAB). The patients were undergoing dialysis at one of five freestanding dialysis units in metropolitan Birmingham (approximately 500 hemodialysis patients). At any given time, approximately 25% of the patients were undergoing dialysis with a catheter (13). All patients with suspected catheter-related bloodstream infection were treated according to a standardized protocol, as described previously (14,15). Catheter-related candidemia was diagnosed when (1) the patient presented with fever or rigors, (2) the blood cultures grew Candida, and (3) there was no source of infection other than the dialysis catheter. Two full-time access coordinators collected data prospectively in a computerized database (16) and managed the infections according to a standardized infection protocol (14). Our microbiology laboratory did not perform routine in vitro susceptibility testing for Candida.
The choice of antifungal therapy was at the discretion of the treating nephrologist. Nine patients were treated with intravenous amphotericin B, and 31 received oral fluconazole. Most patients received a 2-wk course of antifungal drugs. Each nephrologist determined how to manage the catheter (guidewire exchange or removal with delayed placement of a new catheter) on the basis of his or her clinical judgment. Patients were hospitalized only when they had severe symptoms or hemodynamic instability.
Data Analysis
Two full-time dialysis access coordinators maintained a prospective, computerized vascular access database (16). The coordinators recorded the results of the blood cultures, type and duration of antimicrobial therapy, medical complications, and results of subsequent blood cultures. We queried this access database retrospectively to identify all episodes of catheter-related candidemia diagnosed during an 8.5-yr period (September 1, 2000, through February 29, 2008). The UAB electronic medical record was used to extract information on patient demographics, comorbidities, laboratory values, and hospitalizations. Only patients with tunneled dialysis catheters were included.
Approval was obtained from the UAB institutional review board to review the patients’ medical records for research purposes. During the study period, 53 patients received a diagnosis of catheter-related candidemia. When a patient had two or more episodes of catheter-related candidemia, only the first episode was analyzed. We excluded from our analysis 13 patients with concurrent Staphylococcus aureus bacteremia, because this organism is associated with a high frequency of treatment failure (17). The remaining 40 patients with dialysis catheter–related candidemia were the focus of this study. During the 8.5-yr study period, we diagnosed 2143 episodes of catheter-related bloodstream infections, for an average of 252 episodes annually. Candidemia represented only 2% of all episodes of bloodstream infections.
Statistical Analysis
Baseline clinical and demographic features were recorded and compared for the two treatment groups (patients with guidewire catheter exchange versus patients with catheter removal and delayed replacement). The t test and χ2 test were used to compare continuous and categorical values, respectively. The frequency of major complications between outcome groups was compared by means of χ2 test. P < 0.05 was considered statistically significant.
Results
All patients’ catheter-related candidemia was diagnosed by a standardized protocol for management of catheter-related bacteremia at our institution and treated by individual nephrologists using objective outcome measures. The prospective access database documenting treatment and outcomes allowed formal analysis of success rate and complication rate in the subset of patients with candidemia.
The mean age of the study population was 55 ± 14 yr, and 60% were female. Black patients constituted 80% of the study population, reflecting the demographic distribution of our dialysis population. Diabetes was present in approximately half the patients, and hypertension was present in >80%. Vascular disease was common in the study population. The mean catheter age was approximately 7 mo. Hypoalbuminemia was common, with a mean serum albumin concentration of 2.7 g/dl. A total of 58% of the study patients had received antibiotics in the preceding 2 mo for treatment of catheter-related bacteremia. In addition, 25% of the patients had a concomitant bacteremia with their candidemia. The two treatment groups did not differ significantly in their demographics, clinical and laboratory features, or catheter characteristics (Table 1).
Table 1.
Clinical features of the study populationa
| Parameter | Patients with Guidewire Catheter Exchange | Patients with Catheter Removal and Delayed Replacement | P |
|---|---|---|---|
| No of patients | 27 | 13 | |
| Age (yr; mean ± SD) | 56 ± 14 | 51 ± 15 | 0.26 |
| Female gender (n [%]) | 14 (52) | 10 (77) | 0.13 |
| Black race (n [%]) | 22 (81) | 10 (77) | 0.74 |
| Diabetes (n [%]) | 14 (52) | 7 (54) | 0.91 |
| Hypertension (n [%]) | 22 (85) | 11 (79) | 0.81 |
| CAD (n [%]) | 14 (52) | 4 (31) | 0.21 |
| PVD (n [%]) | 13 (48) | 2 (15) | 0.08 |
| CVD (n [%]) | 4 (15) | 4 (31) | 0.39 |
| Serum albumin (g/dl; mean ± SD) | 2.8 ± 0.7 | 2.6 ± 0.6 | 0.39 |
| Catheter age (d; mean ± SD) | 226 ± 200 | 206 ± 280 | 0.80 |
| Concomitant bacteremia (n [%])b | 7 (25) | 3 (23) | 0.85 |
| Bacteremia in preceding 2 mo (n [%])c | 18 (67) | 5 (39) | 0.18 |
CAD, coronary artery disease; CVD, cerebrovascular disease; PVD, peripheral vascular disease.
Concomitant infection: Seven Enterococcus, Two Staphylococcus coagulase negative, and one Stenotrophomonas maltophilia.
Previous bacteremia: Five methicillin-resistant Staphylococcus epidermidis, five Staphylococcus species, five Enterobacter, four Enterococcus, one methicillin-resistant Staphylococcus aureus, one Serratia, one Proteus, and one Klebsiella.
Of the 40 patients with dialysis catheter–related candidemia, 45% grew C. parapsilosis, 22% had C. albicans, 15% grew C. tropicalis, 12% had C. glabrata, and 5% grew other (unknown) Candida species. The distribution of Candida species did not differ significantly between the two treatment groups (Table 2).
Table 2.
Candida species in the study population
| Parameter | Patients with Guidewire Catheter Exchange | Patients with Catheter Removal and Delayed Replacement | P |
|---|---|---|---|
| No. of patients | 27 | 13 | |
| Candida parapsilosis | 14 (52%) | 4 (30%) | 0.20 |
| Candida albicans | 6 (22%) | 3 (23%) | 0.95 |
| Candida tropicalis | 3 (11%) | 3 (23%) | 0.60 |
| Candida glabrata | 2 (7%) | 3 (23%) | 0.37 |
| Candida (unknown species) | 2 (7%) | 0 (0%) | 0.81 |
Of the 40 study patients with dialysis catheter–related candidemia, 27 (67%) underwent guidewire exchange of their infected catheter, and 13 (33%) had catheter removal with delayed placement of a new, tunneled dialysis catheter. The two treatment groups (guidewire exchange and catheter removal with delayed replacement) were similar in age, gender, race, diabetes, hypertension, vascular disease, catheter age, and serum albumin concentration (Table 1). The frequency of patients with previous or concomitant bacteremia was also similar for both treatment groups, as was the relative frequency of Candida species (Table 2).
Only one patient (2.5% of the total) developed a serious complication of candidemia (Table 3). This patient received a diagnosis of Candida endophthalmitis. A recurrent episode of candidemia within 90 d of the initial infection was observed in 15% of the patients in each treatment group. Finally, patient survival was 75% at 6 mo after the episode of candidemia and was similar in both treatment groups.
Table 3.
Comparison of patient outcomes
| Parameter | Patients with Guidewire Catheter Exchange | Patients with Catheter Removal and Delayed Replacement | P |
|---|---|---|---|
| No. of patients | 27 | 13 | |
| Serious complications (n [%]) | 0 (0) | 1 (8) endophthalmitis | 0.15 |
| Recurrent candidemia within 90 d (n [%]) | 4 (15) | 2 (15) | 0.96 |
| Alive at 6 mo (n [%]) | 19 (70) | 11 (85) | 0.33 |
Discussion
We found that dialysis catheter–related candidemia is rare, representing only 2% of all episodes of catheter-related bloodstream infections. In comparison, in a national surveillance program of 4725 bloodstream infections in hospitalized patients, candidemia accounted for 8% of the total (18). The lower frequency of candidemia in dialysis outpatients likely reflects the smaller number of risk factors, such as recent surgery, corticosteroids, malignancy, or organ transplantation (5). Hypoalbuminemia and recent treatment with antibiotics were common in our hemodialysis patients with candidemia and presumably represented risk factors for this complication.
The distribution of Candida species in our hemodialysis population differed substantially from that reported in several large series of hospitalized patients. C. albicans accounted for 48 to 62% of all Candida infections in those series (1,5,7,18,19). In contrast, C. albicans accounted for only 23% of candidemia episodes in our series. It is not clear why the distribution of Candida bloodstream infections differs in hemodialysis patients as compared with the general population. Candidemia caused by C. parapsilosis has been associated with a lower failure to respond to fluconazole as compared with infection caused by C. albicans (23 versus 51%) (7). This difference may explain, in part, the benign course of candidemia in our study population, because C. parapsilosis was the predominant organism. Oral fluconazole is the first-line antifungal agent for treating this infection in outpatients.
Candidemia in our hemodialysis population was associated with a low frequency of serious complications, which occurred in only 2.5% of patients. In contrast, major complications were observed in 15% of 427 hospitalized inpatients with candidemia, including 9% with chorioretinitis. Our hemodialysis patients with candidemia experienced a 25% mortality within 6 mo of diagnosis. Again, this is a much lower rate than that reported in three large series of hospitalized patients with candidemia. Those studies observed a 45% mortality at 30 d (1), 30% mortality at 60 d (5), and 40% mortality at 90 d (7). This difference again suggests that catheter-related candidemia is more benign in hemodialysis outpatients than in hospitalized patients with major risk factors.
Finally, guidewire exchange of the infected catheter was equally effective as catheter removal with delayed replacement while offering the advantage of minimizing the need for catheter procedures. A recurrence of candidemia at 90 d was seen in only 15% of patients, confirming the efficacy of this treatment strategy.
This study has some limitations. First, it was a retrospective study; however, all episodes of catheter-related candidemia, medical management, clinical outcomes, and complications were recorded prospectively in a computerized database by two full-time access coordinators. Thus, it is unlikely that we missed relevant information. Second, the patients were treated at a single medical center, and the results obtained may not generalize to all dialysis centers. Third, there was no uniform treatment plan in terms of antifungal agent or catheter management. Rather, the treating nephrologists managed each episode of candidemia according to their medical judgment. Given that it took 8.5 yr to identify 40 episodes of candidemia in a dialysis center with approximately 500 patients, even a multicenter, randomized clinical trial would require several years to compare the two catheter management strategies.
Conclusions
Our study demonstrated that catheter-related candidemia in hemodialysis patients has a low complication rate of 2.5%. Catheter exchange over a guidewire in conjunction with antifungal therapy offers a high cure rate and a low likelihood of complications. This strategy also simplifies the medical management of catheter-related candidemia by minimizing the number of required interventions and avoiding disruption of the dialysis schedule.
Disclosures
None.
Published online ahead of print. Publication date available at www.cjasn.org.
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