Role of ethylene diamine tetra-acetic acid (EDTA) in catheter lock solutions: EDTA enhances the antifungal activity of amphotericin B lipid complex against Candida embedded in biofilm.

Ethylene diamine tetra-acetic acid (EDTA) is an anticoagulant with antibiofilm-enhancing activity. We therefore used an in vitro biofilm model to determine the activity of amphotericin B lipid complex (ABLC) with or without EDTA against Candida embedded in biofilm on silicone disk surfaces. Clinical blood isolates from cancer patients infected with Candida albicans or Candida parapsilosis were used. Silicone disks were colonised with C. albicans or C. parapsilosis and were sequentially incubated in plasma and then in Mueller-Hinton broth containing 10(5) colony-forming units of each organism. All tests were performed in triplicate. The disks were subsequently placed and incubated for 6h and 8h in solutions containing ABLC alone, EDTA alone, ABLC+EDTA or broth (control). Disks were then removed, sonicated and colony counts were determined. ABLC+EDTA (30 mg/mL) was significantly more effective than ABLC, EDTA and control against C. parapsilosis at 6h (P < or = 0.01) and against C. albicans at 8h (P < or = 0.04). In patients with catheter-related candidaemia when catheter removal is not feasible, the combination of ABLC+EDTA may be considered for antifungal catheter lock solution as part of a catheter salvage therapy.

Amphotericin B lipid complex versus liposomal amphotericin B monotherapy for invasive aspergillosis in patients with hematologic malignancy.

BACKGROUND: Invasive aspergillosis (IA) is a major cause of morbidity and mortality in patients with hematologic malignancy (HM). There are 2 lipid formulations of amphotericin B (AMB) currently in widespread use: AMB lipid complex (ABLC) and liposomal AMB (L-AMB). There are limited data comparing the efficacy and safety of these 2 agents in the treatment of IA in patients with cancer. METHODS: The authors retrospectively studied 381 consecutive patients with HM who had proven or probable IA (according to European Organization for Research and Treatment of Cancer/Mycosis Study Group of the National Institute of Allergy and Infectious Diseases criteria) between June 1993 and December 2005. Of these patients, 158 received primary antifungal therapy with either L-AMB (n=106) or ABLC (n=52). The number of salvage antifungal regimens given were 51 L-AMB regimens and 30 ABLC regimens. It should be noted that the population described in this report was not typical of the hematologic cancer population with IA because of the advanced stage and the severity of the underlying diseases. RESULTS: Risk factors for IA, such as underlying malignancy, neutropenia, steroid use, admission to an intensive care unit, and the presence of graft-versus-host disease, were comparable among the study drug group in the primary or salvage setting. Likewise, comparable distribution of types of Aspergillus species and the presence of disseminated IA were observed. Response to primary or salvage therapy was equally poor in both drug study groups regardless of treatment modality (range, 7.7-15.8% response). In the primary therapy group, ABLC was associated with significantly higher nephrotoxicity than L-AMB (P<.001). CONCLUSIONS: Among patients with HM, primary therapy and salvage therapy for IA with either ABLC or L-AMB as single agent were associated equally with poor outcome. L-AMB appeared to be less nephrotoxic in the primary therapy setting.

Antiseptic effect of a novel alcohol-free mouthwash: a convenient prophylactic alternative for high-risk patients.

We developed an efficacious and non-irritant mouthwash that is alcohol-free and that has a low concentration of chlorhexidine, in order to be used for preventing oral cavity infections in immunocompromised and cancer patients. The novel mouthwash solution was tested for its antimicrobial efficacy against both free floating (planktonic) and the biofilm forms of Candida albicans. The solution was also tested against Klebsiella pneumoniae, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus (MRSA), using a modification of a previously published method. The activity of the novel mouthwash was also compared with that of three commercially available mouthwashes. The experimental mouthwash showed efficacy against C. albicans, both in free-floating form and in biofilm. With higher concentration of chlorhexidine, the solution was also efficacious in inhibiting the growth of K. pneumoniae, P. aeruginosa, and MRSA. The antiseptic activity of the alcohol-free mouthwash against other bacterial organisms and C. albicans was comparable to other commercially available alcohol-based mouthwash solutions. A novel alcohol-free mouthwash solution, that has low concentration of chlorhexidine, showed antiseptic effect against planktonic and biofilm forms of C. albicans and against K. pneumoniae, P. aeruginosa, and MRSA.

The importance of two-step tuberculin skin testing for newly employed healthcare workers.

At the time of hire, 4059 of 6522 healthcare workers required a 2-step tuberculin skin test; 114 workers (2.8%) demonstrated a boosted reaction after the second step. Boosted reactions were significantly associated with male sex and older age. A verbal history of previous tuberculin skin test results was not a reliable indicator of baseline tuberculin skin test status at the time of hire.

Chest tube-related empyema due to methicillin-resistant Staphylococcus aureus: could the chest tube be coated with antiseptics?

We reviewed the epidemiology, clinical manifestations, and outcomes of 3 cases of chest tube-related empyema due to methicillin-resistant Staphylococcus aureus (MRSA). Antiseptic-impregnated chest tubes were inserted in cultures containing MRSA isolates from these 3 patients, and zone of inhibition were measured. Chest tube-related MRSA empyema might complicate tube thoracostomy, and coating the chest tube with antiseptic agents could prevent this complication.

Vancomycin-resistant Enterococcus faecium: catheter colonization, esp gene, and decreased susceptibility to antibiotics in biofilm.

To evaluate the molecular characteristics and antibiotic susceptibility in biofilm of vancomycin-resistant Enterococcus faecium (VREF) organisms that had caused catheter-related VREF bacteremia (VREF-CRB), we compared 22 isolates causing bacteremia obtained from patients with VREF-CRB with 30 isolates from control patients with gastrointestinal colonization by VREF. Using pulsed-field gel electrophoresis, we identified 17 unique strains among the 22 VREF-CRB isolates and 23 strains among the gastrointestinal isolates. The esp gene was detected in 53% (9 of 17) of the VREF-CRB and 61% (14 of 23) of the control strains (P = 0.6). VREF-CRB produced heavier biofilm colonization of silicone disks than did control organisms (P < 0.001). Daptomycin, minocycline, and quinupristin-dalfopristin were each independently more active than linezolid in reducing biofilm colonization by VREF-CRB (P < 0.01), with daptomycin being the most active, followed by minocycline. In conclusion, the esp gene in VREF is not associated with heavy biofilm colonization or catheter-related bacteremia. In biofilm, daptomycin and minocycline were the most active antibiotics against VREF, and linezolid was the least active.

Catheter-related vancomycin-resistant Enterococcus faecium bacteremia: clinical and molecular epidemiology.

OBJECTIVE: To study the clinical and molecular epidemiology of vancomycin-resistant Enterococcus faecium organisms causing catheter-related bacteremia in patients with cancer. DESIGN: Retrospective case-control study. SETTING: University of Texas M. D. Anderson Cancer Center, a tertiary-care hospital in Houston, Texas. PATIENTS: Case-patients were patients with cancer who had catheter-related vancomycin-resistant E. faecium bacteremia and control-patients were patients with cancer and vancomycin-resistant E. faecium gastrointestinal colonization without infection. RESULTS: Ten case-patients with catheter-related vancomycin-resistant E. faecium bacteremia were compared with 30 control-patients with gastrointestinal colonization by vancomycin-resistant E. faecium. Patients with catheter-related vancomycin-resistant E. faecium bacteremia were more likely to have required mechanical ventilation (P < .01), received total parenteral nutrition (P < .01), and had polyurethane catheters (P < .01) inserted in the femoral vein (P = .01). With the use of pulsed-field gel electrophoresis, 4 of the 10 catheter-related vancomycin-resistant E. faecium bacteremia isolates were genetically indistinguishable, whereas only 2 of the 30 control vancomycin-resistant E. faecium isolates displayed this same DNA pattern (P = .03). CONCLUSION: This study suggests that catheter-related vancomycin-resistant E. faecium bacteremia occurs more frequently in patients who receive total parenteral nutrition, mechanical ventilation, and femoral catheters.

Impact of high-dose granulocyte transfusions in patients with cancer with candidemia: retrospective case-control analysis of 491 episodes of Candida species bloodstream infections.

BACKGROUND: The efficacy and feasibility of donor granulocyte transfusion therapy (GTX) have changed considerably over the past four decades. The authors sought to determine the impact of high-dose (approximately 5.5 x 10(10) cells) GTX in patients with candidemia. METHODS: The authors' case-control retrospective analysis comprised 491 consecutive patients treated at The University of Texas M. D. Anderson Cancer Center (Houston,TX) from 1993 to 2000. The cohort included 29 patients with Candida species bloodstream infection who had received GTX and 462 who had not. RESULTS: Both groups were comparable in age, gender, APACHE II score, recent chemotherapy received, broad-spectrum antibiotics, systemic corticosteroids, radiotherapy, intravascular catheter, and concordant antifungal therapy (P > or = 0.1). The patients who received GTX compared with those who did not had a higher incidence of underlying leukemia (86% vs. 29%, P <0.001), persistent neutropenia (59% vs. 18%, P <0.001), non-Candida albicans candidemia (Candida glabrata, 35%; Candida krusei, 31%: 90% vs. 67%, P=0.01), and breakthrough invasive mycosis (62% vs. 23%, P <0.001). Neutropenia was more prolonged in patients who received GTX (28 vs. 10 days, P <0.001). Also, more of the patients who received GTX had received hematopoietic stem cell transplantations (28% vs. 13%, P = 0.03), exposure (within 4 weeks) to antifungals (79% vs. 38%, P <0.001), and stays in critical care units (62% vs. 40%, P=0.02). The overall attributable mortality rate for 25 evaluable recipients of GTX was 48% (n=12), compared with 45% (n=115) of 254 evaluable patients in the control group (P=0.5). Of the 158 patients with leukemia, 25 (16%) had received GTX. In patients with leukemia, more of those who had received GTX experienced disseminated candidiasis (44% vs. 26%; P <0.07) and persistent neutropenia (68% vs. 43%, P <0.02), had candidemia that was more prolonged (> 72 hours, P <0.02), and had more stays in critical care units (68% vs. 44%, P <0.03). On the bases of a reduced multivariate model, a significantly increased risk of death was found for patients with hematopoietic stem cell transplantation (odds ratio [OR]=2.51; 95% confidence interval [95% CI], 0.99-6.31; P <0.05), for patients with persistent neutropenia (OR=4.57; 95% CI, 1.99-10.47; P <0.0003), and for patients with leukemia who also had prolonged candidemia (OR=3.59; 95% CI, 1.61-7.98; P <0.002), disseminated candidiasis (OR=5.19; 95% CI, 2.17-12.42; P <0.0002), or non-C. albicans candidemia (OR=5.02; 95% CI, 1.07-23.64; P <0.04). In patients with leukemia, death was attributable to candidemia in 50% of the GTX recipients, compared with 59% of the non-GTX patients who had received antifungal therapy alone (P=0.4). CONCLUSIONS: Despite the presence of multiple predictors of increased mortality, high-dose GTX therapy in these high-risk patients with cancer was associated with better than expected survival rates.

Multiple-species candidemia in patients with cancer.

BACKGROUND: Candidemia is a common cause of bloodstream infections in patients with cancer, with the majority of these infections being caused by a single Candida species. Studies of multiple-species candidemia (MSC) have rarely been reported. METHODS: The authors identified 33 patients with cancer who had candidemia (diagnosed between 1993 and 2000) caused by more than 1 Candida species. This group of 33 patients was compared with a control group of 66 patients with cancer who had C. albicans candidemia that arose soon before or soon after each case of MSC that was investigated in the current study. RESULTS: Patients with MSC, compared with control patients, were more likely to have leukemia (33% vs. 8%; P = 0.001), to have had prolonged neutropenia before the onset of their infection (mean +/- standard deviation, 10 +/- 17 days vs. 3 +/- 6 days; P = 0.02), and to have received chemotherapy within 1 month before their infection (42% vs. 18%; P = 0.01). Patients with MSC also had higher Acute Physiology and Chronic Health Evaluation II scores at the onset of infection (score > or = 16, 45% vs. 26%; P = 0.05) and were more likely to have received previous antifungal prophylaxis compared with patients who had candidemia caused by C. albicans (33% vs. 11%; P = 0.006). The response of C. albicans candidemia to single-agent antifungal therapy was significantly better than that of MSC (69% vs. 35% P = 0.004). CONCLUSIONS: In patients with cancer, MSC was more likely to occur as breakthrough candidemia, predominantly in those with leukemia and prolonged neutropenia, and was associated with suboptimal responses to single-agent antifungal therapy.

Clinical-use-associated decrease in susceptibility of vancomycin-resistant Enterococcus faecium to linezolid: a comparison with quinupristin-dalfopristin.

The susceptibility of 135 vancomycin-resistant Enterococcus faecium bacteremic isolates to linezolid and quinupristin-dalfopristin was determined. All were susceptible to linezolid, while 88% were susceptible to quinupristin-dalfopristin prior to the clinical use of the drugs at our hospital. More than 6 months after their clinical use, a decrease in susceptibility was noted for only linezolid at 83%. This was related in part to a single G2576U gene mutation in domain V of the 23S rRNA gene.

Differential time to positivity: a useful method for diagnosing catheter-related bloodstream infections.

BACKGROUND: Catheter-related bloodstream infections are associated with recognized morbidity and mortality, especially in critically ill patients. Accurate diagnosis of such infections results in proper management of patients and in reducing unnecessary removal of catheters. OBJECTIVE: To evaluate differential time to positivity as a method for diagnosing catheter-related bacteremias caused by both short-term and long-term use of central venous catheters. DESIGN: Prospective study design. SETTING: M.D. Anderson Cancer Center, Houston, Texas, a tertiary care cancer center. PATIENTS: All patients, between September 1999 and November 2000, who had the same organism isolated from blood cultures drawn simultaneously through the central venous catheter and the peripheral vein. MEASUREMENTS: Time necessary for the blood cultures from the central venous catheter and the peripheral vein to become positive, as well as other relevant patient information. RESULTS: 191 bloodstream infections with positive simultaneous central venous catheter and peripheral vein blood cultures were included. One hundred eight patients had catheter-related bacteremias, and 83 had non-catheter-related bacteremias. Catheter-related bacteremias were more frequently caused by staphylococci and less likely to be associated with underlying hematologic malignant conditions, neutropenia, and longer duration of hospitalization. As a diagnostic tool for catheter-related bacteremia (using a composite definition reference standard according to the Infectious Diseases Society of America guidelines), differential time to positivity of 120 minutes or more was associated with 81% sensitivity and 92% specificity for short-term catheters and 93% sensitivity and 75% specificity for long-term catheters. CONCLUSION: Differential time to positivity of 120 minutes or more is highly sensitive and specific for catheter-related bacteremia in patients who have short- and long-term catheters.

Antibiotic-impregnated catheters associated with significant decrease in nosocomial and multidrug-resistant bacteremias in critically ill patients.

OBJECTIVE: To evaluate the impact of using central venous catheters (CVCs) impregnated with the combination of minocycline and rifampin on nosocomial bloodstream infections (BSIs), morbidity, and mortality in cancer patients in the ICU. DESIGN: Prospective surveillance study consisting of the following two time periods: September 1997 through August 1998 (ie, fiscal year [FY] 1998); and from September 1998 through August 1999 (ie, FY 1999). SETTING: ICUs of a tertiary care hospital in Houston, TX. PATIENTS: Cancer patients in the medical ICU (MICU) and surgical ICU (SICU). INTERVENTIONS: ICUs started using CVCs impregnated with the minocycline-rifampin combination at the beginning of FY 1999. MEASUREMENTS AND MAIN RESULTS: The rates of nosocomial BSIs and other patients' characteristics were compared for the two study periods to determine the impact of using the impregnated catheters in the ICU. Patients' characteristics, including antibiotic use, were comparable for the two study periods in both the MICU and the SICU. The rate of nosocomial BSIs in the MICU unit decreased from 8.3 to 3.5 per 1,000 patient-days (p < 0.01), and decreased in the SICU from 4.8 to 1.3 per 1,000 patient-days (p < 0.01) in FY 1999. Nosocomial vancomycin-resistant enterococcus (VRE) bacteremia also decreased significantly (p = 0.004). Length of stay in the MICU and SICU significantly decreased in FY 1999 (p < 0.01 and p = 0.03, respectively). The duration of hospitalization decreased for MICU and SICU patients (p = 0.06 and p < 0.01, respectively). The rate of catheter-related infections decreased from 3.1 to 0.7 per 1,000 patient-days in FY 1999 (p = 0.02). The decrease in infections resulted in net savings of at least $1,450,000 for FY 1999. CONCLUSIONS: The use of antibiotic-impregnated CVCs in the MICU and SICU was associated with a significant decrease in nosocomial BSIs, including VRE bacteremia, catheter-related infections, and lengths of hospital and ICU stays.

Treatment of febrile neutropenic patients with cancer who require hospitalization: a prospective randomized study comparing imipenem and cefepime.

BACKGROUND: The objective of the current study was to compare the efficacy and safety of imipenem and cefepime in the treatment of adult patients with cancer who had fever and neutropenia requiring hospitalization according to Infectious Disease Society of America criteria. METHODS: In the current prospective randomized clinical trial at a university-affiliated tertiary cancer center, adult patients with cancer who had fever (> or = 38.3 degrees C or > or = 38.0 degrees C for > 2 hours) and neutropenia (< or = 500/mm(3) or < 1000/mm(3) but declining) requiring hospitalization were randomized to receive either cefepime or imipenem. Vancomycin or amikacin was added on suspicion of gram-positive or gram-negative bacterial infection, respectively. RESULTS: Patients who received an imipenem regimen or a cefepime regimen were comparable in terms of age, gender, underlying malignancy, prior transplantation, degree and trend of neutropenia, and presence of central venous catheters (P > or = 0.3). An intent-to-treat analysis showed a 68% response rate to the imipenem regimen, compared with a 75% response rate to the cefepime regimen (P = 0.2). The rates of antibiotic-related adverse events and superinfections also were comparable (P = 0.6). There was no difference in response among patients who received imipenem or cefepime alone compared with patients who also received vancomycin or amikacin (P = 1.0). Leukemia was the only independent risk factor associated with a poor outcome (odds ratio, 4.6; 95% confidence interval, 1.9-10.7; P < 0.0001). CONCLUSIONS: Imipenem and cefepime had similar efficacy and safety profiles in the treatment of adult cancer patients with fever and neutropenia who required hospitalization. The addition of either vancomycin or amikacin may not be necessary.

Nocardiosis in cancer patients.

Nocardiosis (NOC) is an important cause of infection in immunocompromised patients. However, large series in patients with cancer have not been described. We review the records of patients with cancer and NOC who were evaluated at The University of Texas M. D. Anderson Cancer Center, Houston, Texas, between 1988 and 2001, and we describe the incidence, microbiologic and clinical characteristics, treatment, and outcome of NOC in this population. Forty-two patients with a total of 43 episodes of NOC were identified (incidence of 60 cases of NOC per 100,000 admissions). Twenty-seven patients (64%) had hematologic malignancies. In 13 patients, NOC complicated bone marrow transplantation. Neutropenia was observed in 4 (10%) of 40 episodes with information available, and lymphopenia in 20 (50%) of 40 episodes. Patients had received steroids for 25 episodes (58%) and had received chemotherapy for 10 episodes (23%) within 30 days before the onset of NOC. Nine episodes of breakthrough NOC were identified in 7 (23%) of the 40 patients with information available. Pulmonary NOC was seen in 30 (70%) of 43 cases; soft-tissue NOC in 7 (16%); central venous catheter-related nocardemia in 3 (7%); and disseminated NOC, central nervous system NOC, and a perinephric abscess each in 1 (2%). Twenty-three percent of patients with pulmonary NOC had an acute presentation. complex was the most common causative species (77%). Therapy for NOC was mainly concurrent trimethoprim/ sulfamethoxazole and either a tetracycline or a beta-lactam. The median duration of treatment was 113 days (range, 10-600 d). Nine (60%) of 15 patients with outcome data died from NOC. NOC, although infrequent, is an important cause of morbidity and mortality in patients with cancer. It has pleomorphic manifestations, and it can be seen as a breakthrough infection. The present study confirms that timely diagnosis, the site of NOC, the type of, the presence of comorbidities, and cytomegalovirus coinfection influence the outcome of patients with cancer and NOC.

Intravascular catheter-related infections: new horizons and recent advances.

BACKGROUND: Central venous catheters have become essential devices for the management of critically and chronically ill patients; however, their use is often complicated by catheter-related bloodstream infections (CRBSIs), many of which could be prevented. METHODS: This report is based on a literature review of more than 100 published articles in intravascular catheter-related infections. This review focuses on the most recent advances in the methods of diagnosis of CRBSI as they relate to its pathogenesis and on novel preventive techniques and approaches to management. RESULTS: Catheter-related bloodstream infections may be diagnosed by different methods, including simultaneous quantitative blood cultures, with the central blood culture yielding at least 5-fold colony-forming units greater than the peripheral blood culture, and simultaneous blood cultures, whereby the catheter-drawn blood culture becomes positive at least 2 hours before the peripheral blood culture. Novel preventive techniques include the use of ionic silver, an anticoagulant/antimicrobial flush solution, a new aseptic hub, and antimicrobial impregnation of catheters and dressings. Management of CRBSIs should be based on whether the infection is complicated or uncomplicated. CONCLUSIONS: Novel technologies that have been proved to aid in the diagnosis and prevention of CRBSIs should be considered in clinical practice. The management approach should be based on the type of microorganism causing the infection and on whether the infection is complicated or uncomplicated.

The epidemiology of Candida glabrata and Candida albicans fungemia in immunocompromised patients with cancer.

PURPOSE: Candida glabrata is an increasing cause of candidemia, especially at cancer and bone marrow transplant centers where fluconazole is used for antifungal prophylaxis. This yeast is less susceptible to fluconazole in vitro than is Candida albicans. We compared the characteristics of patients who had C. glabrata and C. albicans candidemia at a large cancer center. SUBJECTS AND METHODS: We searched the microbiological laboratory reports and identified 116 cases of C. glabrata candidemia between 1993 and 1999. The 116 cases of C. albicans candidemia that occurred most closely in time (before or after each case of C. glabrata candidemia) served as the control group. Data were collected from patients' medical records. RESULTS: When compared with patients who had C. albicans infection, patients with C. glabrata candidemia more often had an underlying hematologic malignancy (68 [59%] vs. 26 [22%], P = 0.0001), had an Acute Physiology and Chronic Health Evaluation (APACHE) II score > or =16 (55 [48%] vs. 28 [25%], P = 0.0002), and received fluconazole prophylaxis (57 [49%] vs. 8 [7%], P = 0.0001). Patients with C. albicans candidemia more often had concomitant infections (101 [87%] vs. 78 [67%], P = 0.0003) and septic thrombophlebitis (11 [10%] vs. 2 [2%], P = 0.01). Among patients treated with antifungal therapy, those with C. albicans candidemia had a significantly greater overall response to therapy (83/104 [80%] vs. 60/97 [62%], P = 0.005) and to primary therapy (74/104 [71%] vs. 45/97 [46%], P = 0.0003). Amphotericin B preparations were not more effective than fluconazole (19/45 [42%] vs. 20/38 [53%], P = 0.5) in patients with C. glabrata candidemia. Fluconazole was less effective against C. glabrata than against C. albicans (20/38 [53%] vs. 57/74 [77%], P = 0.008). CONCLUSION: C. glabrata has emerged as an important cause of candidemia, especially among neutropenic patients who receive fluconazole prophylaxis.