Glyceryl trinitrate complements citrate and ethanol in a novel antimicrobial catheter lock solution to eradicate biofilm organisms.

Antimicrobial catheter lock therapy is practiced to prevent lumenal-sourced infections of central venous catheters. Citrate has been used clinically as an anticoagulant in heparin-free catheter locks. Ethanol has also been widely studied as an antimicrobial lock solution component. This study reports on the synergy of glyceryl trinitrate (GTN) with citrate and ethanol in rapidly eradicating methicillin-resistant Staphylococcus aureus, methicillin-resistant Staphylococcus epidermidis, Pseudomonas aeruginosa, and Candida albicans biofilms in an in vitro model for catheter biofilm colonization. GTN has a long history of intravenous use as a hypotensive agent. It is potentially attractive as a component of a catheter lock solution because its physiologic half-life is quite short and its metabolic pathways are known. A lock containing 7% citrate and 20% ethanol required 0.01% GTN to fully eradicate biofilms of all test organisms within 2 h in the model. This GTN concentration is below the levels where clinically significant hypotensive effects are expected.

A pilot study of a triple antimicrobial-bonded Dacron graft for the prevention of aortic graft infection.

OBJECTIVE: Perioperative infection of an aortic graft is one of the most devastating complications of vascular surgery, with a mortality rate of 10% to 30%. The rate of amputation of the lower limbs is generally >25%, depending on the graft material, the location of the graft and infection, and the bacterial virulence. In vitro studies suggest that an antibiotic-impregnated graft may help prevent perioperative graft infection. In a pilot animal study, we tested a locally developed technique of bonding Dacron aortic grafts with three antimicrobial agents to evaluate the ensuing synergistic preventive effect on direct perioperative bacterial contamination. METHODS: We surgically implanted a 6-mm vascular knitted Dacron graft in the infrarenal abdominal aorta of six Sinclair miniature pigs. Two pigs received unbonded, uninoculated grafts; two received unbonded, inoculated grafts; and two received inoculated grafts that were bonded with chlorhexidine, rifampin, and minocycline. Before implantation, the two bonded grafts and the two unbonded grafts were immersed for 15 minutes in a 2-mL bacterial solution containing 1 to 2 × 10(7) colony-forming units (CFU)/mL of Staphylococcus aureus (ATCC 29213). Two weeks after graft implantation, the pigs were euthanized, and the grafts were surgically excised for clinical, microbiologic, and histopathologic study. RESULTS: The two bonded grafts treated with S aureus showed no bacterial growth upon explant, whereas the two unbonded grafts treated with S aureus had high bacterial counts (6.25 × 10(6) and 1.38 × 10(7) CFU/graft). The two control grafts (unbonded and untreated) showed bacterial growth (1.8 × 10(3) and 7.27 × 10(3) CFU/graft) that presumably reflected direct, accidental perioperative bacterial contamination; S cohnii ssp urealyticus and S chromogenes, but not S aureus, were isolated. The histopathologic and clinical data confirmed the microbiologic findings. Only pigs that received unbonded grafts showed histopathologic evidence of a perigraft abscess. CONCLUSIONS: Our results suggest that bonding aortic grafts with this triple antimicrobial combination is a promising method of reducing graft infection resulting from direct postoperative bacterial contamination for at least 2 weeks. Further studies are needed to explore the ability of this novel graft to combat one of the most feared complications in vascular surgery.

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.

Orthopaedic metal devices coated with a novel antiseptic dye for the prevention of bacterial infections.

Gendine is a novel antiseptic dye with broad-spectrum antimicrobial activity that may be used to coat plastics and metal devices. Our objective was to determine the efficacy of gendine-coated orthopaedic metal devices in preventing methicillin-resistant Staphylococcus aureus (MRSA) colonisation. Stainless steel and titanium Schanz rods were coated with gendine. The zone of inhibition (ZoI) around the rods with and without gamma-irradiation was determined by a modified Kirby-Bauer method. A previously published bioprosthetic biofilm colonisation model, modified Kuhn's method, was used to determine the adherence of MRSA to coated and uncoated rods, with and without irradiation, after insertion into bovine bone and after 3 months shelf life followed by 2 weeks of immersion in serum. The gendine-coated Schanz metal rods showed a net ZoI of 16 mm against MRSA before and after irradiation. Gendine-coated rods showed no biofilm formation (0 colony-forming units (CFU)), which was a significant reduction (P<0.001) compared with uncoated controls (>5000 CFU). Coated rods exposed to high-dose gamma-irradiation and coated rods drilled into bone also showed significant efficacy (P<0.001) in preventing biofilm adherence. After 2 weeks, gendine-coated rods maintained significant durability (P<0.01), resulting in 90% reduction in MRSA biofilm adherence compared with uncoated control rods. Results indicate that gendine-coated metal rods are highly efficacious in the prevention of MRSA biofilm.

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.

Long-term silicone central venous catheters impregnated with minocycline and rifampin decrease rates of catheter-related bloodstream infection in cancer patients: a prospective randomized clinical trial.

PURPOSE: To evaluate the efficacy of long-term nontunneled silicone catheters impregnated with minocycline and rifampin (M-R) in reducing catheter-related bloodstream infections. PATIENTS AND METHODS: This prospective, randomized, double-blind clinical trial was conducted at M.D. Anderson Cancer Center, a tertiary care hospital in Houston, TX. All patients in the trial had a malignancy. RESULTS: Between September 1999 and May 2002, 356 assessable catheters were used: 182 M-R and 174 nonimpregnated. The patients' characteristics were comparable between the two study groups. The mean (+/- standard deviation) duration of catheterization with M-R catheters was comparable to that of nonimpregnated catheters (66.21 +/- 30.88 v 63.01 +/- 30.80 days). A total of 17 catheter-related bloodstream infections occurred during the course of the study. Three were associated with the use of M-R catheters and 14 were associated with the nonimpregnated catheters, with a rate of catheter-related bloodstream infection of 0.25 and 1.28/1,000 catheter-days, respectively (P = .003). Gram-positive cocci accounted for the majority of the organisms causing the infections. There were no allergic reactions associated with M-R catheters. CONCLUSION: Long-term nontunneled central venous catheters impregnated with minocycline and rifampin are efficacious and safe in reducing catheter-related bloodstream infections in cancer patients.

Impact of surveillance for vancomycin-resistant enterococci on controlling a bloodstream outbreak among patients with hematologic malignancy.

OBJECTIVE: To determine the impact of stool surveillance cultures of critically ill patients on controlling vancomycin-resistant enterococci (VRE) outbreak bacteremia. DESIGN: Stool surveillance cultures were performed on patients who had hematologic malignancy or were critically ill at the time of hospital admission to identify those colonized with VRE. Hence, contact isolation was initiated. SETTING: A tertiary-care cancer center with a high prevalence of VRE. PARTICIPANTS: All patients with hematologic malignancy who were admitted to the hospital as well as all of those admitted to the intensive care unit were eligible. RESULTS: Active stool surveillance cultures performed between 1997 and 2001 decreased the incidence density of VRE bacteremias eightfold while vancomycin use remained constant. In fiscal year (FY) 1997 and FY 1998, there were five and three VRE outbreak bacteremias, respectively. The outbreak clones were responsible for infection in 69% of those patients with VRE bacteremia. However, the stool surveillance program resulted in the complete control of VRE bacteremia by FY 1999 until the end of the study. CONCLUSION: Despite the steady use of vancomycin, the active surveillance program among high-risk patients with hematologic malignancy and those who were critically ill resulted in the complete control of VRE outbreak bacteremia at our institution.

Panton Valentine Leukocidin exotoxin has no effect on the outcome of cancer patients with methicillin-resistant Staphylococcus aureus (MRSA) infections.

The presence of Panton-Valentine leukocidin (PVL) gene in methicillin-resistant Staphylococcus aureus (MRSA) infections has been associated with high severity and mortality rates. In this study we evaluated the effect of PVL on outcome in cancer patients with MRSA infections.We retrospectively reviewed the records of 173 cancer patients diagnosed with MRSA pneumonia (n = 47), skin and soft tissue infections (n = 77), and bacteremia (n = 49) between September 2003 and September 2007 at M. D. Anderson Cancer Center. We obtained demographic and clinical data and tested isolates for the presence of PVL. The data were compared between patients with PVL (+) and those with PVL (-) strains. Statistical methods for comparison included Cochran-Mantel-Haenszel tests, 2-way nonparametric analysis of variance, chi-square or Fisher exact tests, and Wilcoxon rank sum tests. All tests were 2-sided with a significance level of 0.05.Seventy patients with PVL (+) strains and 103 patients with PVL (-) strains were included in our study. Fewer PVL (+) patients had pneumonia than did PVL (-) patients (14% vs. 36%, p = 0.002). PVL (-) patients were more likely to have concomitant infections (35% vs. 17%, p = 0.012). The 2 groups were similar in terms of fever, sepsis, vasopressor use, mechanical ventilation, antibiotics response, infection relapse, death, and death due to MRSA. In a skin and soft tissue subset analysis, PVL (+) patients were more likely to have solid tumors (73% vs. 47%, p = 0.02) and less likely to have fever (20% vs. 44%, p = 0.02) and sepsis (12% vs. 36%, p = 0.013). There were no differences in outcome between patients with pneumonia and bacteremia; however, most patients with pneumonia were PVL (-) (79% vs. 21%). Among the 73 patients who received vancomycin and the 20 who received linezolid, there was no difference in response to treatment, regardless of PVL status or neutropenia. In conclusion, the presence of the PVL gene had no negative effect on cancer patients with health care-associated MRSA.

The prevention of biofilm colonization by multidrug-resistant pathogens that cause ventilator-associated pneumonia with antimicrobial-coated endotracheal tubes.

Ventilator-associated pneumonia (VAP) continues to be the nosocomial infection associated with the highest mortality in critically ill patients. Since silver-coated endotracheal tubes (ETT) was shown in a multicenter prospective randomized trials to decrease the risk of VAP, we compared the efficacy of two antiseptic agents such as gardine- and gendine-coated ETTs with that of silver-coated ETTs in preventing biofilm. The ETTs were tested for their ability to prevent the biofilm formation of methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae, Enterobacter cloacae, and Candida albicans. Scanning electron microscopy studies revealed a heavy biofilm on uncoated and silver-coated ETT but not on the gardine-coated ETT. The gardine and gendine ETTs completely inhibited the formation of biofilms by all organisms tested and were more effective in preventing biofilm growth than the silver ETTs (p < 0.001). The gardine- and gendine-coated ETTs were more durable against MRSA than either the silver-coated or uncoated ETTs for up to 2 weeks (p < 0.0001). We have therefore shown that gardine- and gendine-coated ETTs are superior to silver-coated ETTs in preventing biofilm. Future animal and clinical studies are warranted to determine whether the gardine- and gendine-coated ETTs can significantly reduce the risk of VAP.

Outbreak of community-acquired methicillin-resistant Staphylococcus aureus skin infections among health care workers in a cancer center.

BACKGROUND: The incidence of community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) soft tissue infections is rising. However, CA-MRSA outbreaks among health care workers (HCWs) are rarely reported. We describe 3 clusters of CA-MRSA soft tissue infections among HCWs and the subsequent transmission to a patient. METHODS: The first cluster of boils occurred in 4 employees who worked in the ambulatory treatment clinic (area A) and 1 patient (PA1) who frequently visited area A. Three employees (EA1, EA2, and EA3) and PA1 had positive cultures. Twelve employees in 2 geographically separate diagnostic imaging areas (areas B and C) reported recent or current boils of whom EB1, EB2, EB3, and EC1 had positive cultures. Molecular subtyping using pulse-field gel electrophoresis (PFGE) was performed on all 8 isolates and confirmed by the Centers for Disease Control and Prevention laboratory. RESULTS: Relatedness of the MRSA strain was confirmed by PFGE in 7 of 8 isolates. Only EB3 was not related to the prototype CA-MRSA strain. All 7 related MRSA strains contained the typical genetic organization of staphylococcal cassette chromosome (SCC)-mec type IVa plus genes encoding Panton-Valentine Leukocidin. EB3's strain contained SCC-mec type II and was Panton-Valentine Leukocidin negative. A total of 171 questionnaires was sent. Nine of the 85 HCWs who responded reported a recent or current history of boils. Infection control conducted an education program for employees in areas A, B, and C. CONCLUSION: Early identification and control of CA-MRSA infections among HCWs is important to limit horizontal transmission to patients. Future efforts should include educational programs and guidelines for reporting and treating HCWs with MRSA infections.

The role of interventional molecular epidemiology in controlling clonal clusters of multidrug resistant Pseudomonas aeruginosa in critically ill cancer patients.

BACKGROUND: Pseudomonas aeruginosa is one of the leading causes of hospital-acquired infections in intensive care units (ICUs). The objective was to evaluate the impact of molecular identification of clonal multidrug-resistant (MDR) P aeruginosa strains and the implementation of infection control measures. METHODS: One hundred seventy-seven strains from ICU patients infected or colonized with MDR P aeruginosa from May 2001 to April 2006 were collected. In vitro susceptibility to 16 antibiotics was done. Pulsed-field gel electrophoresis was performed to identify clonal strains. Nosocomial outbreak was defined as the presence of > or =3 MDR P aeruginosa over < or =3 consecutive months. RESULTS: During the 5 years of the study, 25 infected and 14 colonized patients with a clonal strain of MDR P aeruginosa were distributed among 5 episodic clusters. These strains were only susceptible to ceftazidime and colistin. Molecular biology identification, diligent monitoring, and multidisciplinary infection control interventions were implemented to suppress this clonal strain after each cluster. Even more, after the last outbreak (June-August 2005), the infection control measures were able to reduce the MDR P aeruginosa to zero during the last 8 months of this study. CONCLUSION: Interventional molecular epidemiology combined with early identification, monitoring, and implementation of multidisciplinary infection control measures can control temporarily the transmission of MDR P aeruginosa infection in ICUs.

Efficacy of novel antimicrobial gloves impregnated with antiseptic dyes in preventing the adherence of multidrug-resistant nosocomial pathogens.

BACKGROUND: Contaminated gloves are a major source of transmission of bacteria in the hospital and food industry. We investigated the efficacy of gloves impregnated with a combination of antiseptics consisting of brilliant green dye and chlorhexidine (Gardine). METHODS: Gardine-coated and uncoated 1-cm(2) segments of latex examination and nitrile examination gloves (Spontex, Columbia, TN) were exposed to 1.5 x 10(8) colony-forming units (CFU)/mL methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci, multidrug resistant (MDR) Escherichia coli, MDR-Acinetobacter baumannii, or Candida albicans as indicated by our brief exposure method. At least 3 glove segments were tested in each group, and growth was scored as mean CFU/cm(2). Segments were dried for various time periods (30 seconds, 10 minutes, 30 minutes, and 1 hour) and streaked face down on agar plates. Plates were incubated overnight at 37 degrees C, and growth was quantitated. RESULTS: Gardine-coated latex and nitrile gloves showed significant reduction, an average of 6 logs and 5 logs, respectively, within 30 seconds or 10 minutes when tested against MRSA, vancomycin-resistant enterococci, MDR-E coli, MDR-Acientobacter, and C albicans. Complete kill, 8-log reduction, was seen within 30 seconds for MRSA and E coli in both Gardine-coated latex and nitrile gloves. CONCLUSION: Gloves impregnated with Gardine antiseptic dye were highly efficacious in preventing contamination of nosocomial-resistant pathogens on the outer surface of glove and may be useful in the food industry or clinical setting.

The role of molecular methods in the prevention of nosocomial methicillin-resistant Staphylococcus aureus clusters in cancer patients.

In 2002, an increased incidence of nosocomial methicillin-resistant Staphylococcus aureus (MRSA) in our institution triggered a conventional investigation that failed to identify a common source. Molecular typing of the 70 nosocomial MRSA isolates obtained identified a predominant health care-associated clone A in the first trimester. Aggressive infection control measures led to a significant decrease in the number of isolates per 10,000 hospital days between the first trimester and the last 2 trimesters of 2003 (6.4 vs 3.8; P = .04). This was attributed to a decrease in clone A: SCCmec II, USA100, PVL gene-negative (2.3 per 10.000 patient-days vs 0.1 per 10,000 patient-days; P = .004). However, in 2003, 23% of the nosocomial isolates were SCCmec IV, USA300, PVL gene-positive. At that time, molecular methods allowed the detection and prevention of a nosocomial MRSA outbreak caused by a health care-associated clone; however, the community strains (SCCmec IV) have become a frequent cause of nosocomial infection in our institution.

Optimal antimicrobial catheter lock solution, using different combinations of minocycline, EDTA, and 25-percent ethanol, rapidly eradicates organisms embedded in biofilm.

Antimicrobial lock solutions may be needed to salvage indwelling catheters in patients requiring continuous intravenous therapy. We determined the activity of minocycline, EDTA, and 25% ethanol, alone or in combination, against methicillin-resistant Staphylococcus aureus and Candida parapsilosis catheter-related bloodstream infection strains in two established models of biofilm colonization. Biofilm-colonized catheter segments from a modified Robbins device and a silicone disk biofilm colonization model were exposed to these antimicrobial agents for 15 or 60 min, respectively. After exposure, segments were sonicated and cultured. To determine regrowth after incubation at 37 degrees C, following the brief exposure to the antimicrobial agents, an equal number of segments were washed, reincubated for 24 h, and then sonicated and cultured. The triple combination of minocycline-EDTA (M-EDTA) in 25% ethanol was the only antimicrobial lock solution that completely eradicated S. aureus and C. parapsilosis in biofilm of all segments tested in the two models, and it completely prevented regrowth. In addition, M-EDTA in 25% ethanol was significantly more effective in rapidly eradicating the growth or regrowth of methicillin-resistant S. aureus and C. parapsilosis biofilm colonization in the two models than the other solutions--minocycline, EDTA, M-EDTA, 25% ethanol, and EDTA in ethanol. We conclude that M-EDTA in 25% ethanol is highly effective at rapidly eradicating S. aureus and C. parapsilosis embedded in biofilm adhering to catheter segments.

Comparative activities of daptomycin, linezolid, and tigecycline against catheter-related methicillin-resistant Staphylococcus bacteremic isolates embedded in biofilm.

In the setting of catheter-related bloodstream infections, intraluminal antibiotic lock therapy could be useful for the salvage of vascular catheters. In this in vitro study, we investigated the efficacies of the newer antibiotics daptomycin, linezolid, and tigecycline, in comparison with those of vancomycin, minocycline, and rifampin, against methicillin-resistant Staphylococcus aureus (MRSA) embedded in biofilm. We also assessed the emergence of MRSA strains resistant to these antibiotics, alone or in combination with rifampin, after 4-hour daily use for catheter lock therapy. Minocycline, daptomycin, and tigecycline were more efficacious in inhibiting MRSA in biofilm than linezolid, vancomycin, and the negative control (P < 0.001) after the first day of exposure to these antibiotics, with minocycline being the most active, followed by daptomycin and then tigecycline, and with vancomycin and linezolid lacking activity, similar to the negative control. After 3 days of 4-hour daily exposures, daptomycin was the fastest in eradicating MRSA from biofilm, followed by minocycline and tigecycline, which were faster than linezolid, rifampin, and vancomycin (P < 0.001). When rifampin was used alone, it was the least effective in eradicating MRSA from biofilm after 5 days of 4-hour daily exposures, as it was associated with the emergence of rifampin-resistant MRSA. However, when rifampin was used in combination with other antibiotics, the combination was significantly effective in eliminating MRSA colonization in biofilm more rapidly than each of the antibiotics alone. In summary, daptomycin, minocycline, and tigecycline should be considered further for antibiotic lock therapy, and rifampin should be considered for enhanced antistaphylococcal activity but not as a single agent.

Comparative in vitro efficacies and antimicrobial durabilities of novel antimicrobial central venous catheters.

We investigated the efficacies and durability of novel antimicrobial central venous catheters (CVCs) in preventing the adherence of microbial organisms to the surfaces of the CVCs. Novel antimicrobial CVCs investigated in this in vitro study were impregnated with antibiotics (minocycline and rifampin), with Oligon agent (silver, platinum, and carbon black), with approved antiseptics (chlorhexidine and silver sulfadiazine), or with a novel antiseptic agent, gendine, which contains gentian violet and chlorhexidine. When tested against methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa, gendine-coated CVC segments provided protection against bacterial adherence significantly more than all other types of tested CVCs (P < 0.05). Gendine-coated CVCs also provided better protection against Candida albicans and Candida parapsilosis than CVCs impregnated with antibiotics or with silver, platinum, and carbon (P < 0.02). After 28 days of being soaked in serum, the CVCs impregnated with chlorhexidine and silver sulfadiazine and the CVCs impregnated with silver, platinum, and carbon had lost antimicrobial activity against MRSA, P. aeruginosa, and C. parapsilosis, and the CVCs impregnated with minocycline and rifampin had lost activity against P. aeruginosa and C. parapsilosis. The CVCs impregnated with gendine maintained antimicrobial activities against MRSA, P. aeruginosa, and C. parapsilosis after 28 days of being soaked in serum. Central venous catheters impregnated with the novel investigational antiseptic gendine showed in vitro efficacy and provided protection against bacterial adherence more than other approved novel antimicrobial-coated CVCs.

A rapid method of impregnating endotracheal tubes and urinary catheters with gendine: a novel antiseptic agent.

OBJECTIVES: To test the efficacy of gendine, a novel antiseptic, containing Gentian Violet and chlorhexidine, in coating different medical devices, including endotracheal tubes (ETT) and urinary catheters (UC). METHODS: We determined the antimicrobial efficacy and cytotoxicity of ETT and UC segments coated, through an instant dip method, with gendine. Using the modified Kirby-Bauer method, gendine-coated devices showed zones of inhibition of >/=15 mm against methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa, Escherichia coli and Candida parapsilosis. RESULTS: Gendine-coated endotracheal tubes (GND-ETT) soaked in bronchoalveolar fluid (BAL) and incubated at 37 degrees C maintained a zone of inhibition of >/=15 mm against MRSA and P. aeruginosa for at least 3 weeks. Similarly, gendine-coated urinary catheters (GND-UC), soaked in urine, maintained a zone of inhibition of >/=15 mm against E. coli for 8 weeks. Using the minimum essential media elution method in mouse fibroblast cells, GND-ETT and GND-UC were found to be non-cytotoxic. Gendine-coated UC significantly reduced the amount of viable MRSA, E. coli or C. parapsilosis organisms adhering to their surfaces when compared with silver/hydrogel-coated urinary catheters or control uncoated catheters (P < 0.01). Similarly GND-ETT significantly reduced the adherence of the same organisms as well as P. aeruginosa when compared with control (P

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.

Risk factors for infections with multidrug-resistant Pseudomonas aeruginosa in patients with cancer.

BACKGROUND: Pseudomonas aeruginosa is responsible for a wide range of infections. In immunocompromised patients with cancer, the emergence of multidrug resistant P. aeruginosa may have grave consequences. METHODS: Patients with cancer who were infected with multidrug-resistant P. aeruginosa with polyclonal DNA restriction patterns were used as the case group. Two control groups were used: one group of cancer patients who were infected with multidrug-susceptible P. aeruginosa and another group of cancer patients who had the same underlying disease and the same intensive care unit exposure as patients in the case group but who were not infected or colonized by P. aeruginosa. RESULTS: Risk factors that were associated significantly with multidrug-resistant P. aeruginosa infection were the use of carbapenem for > or = 7 days, a history of P. aeruginosa infection during the preceding year, and a history of chronic obstructive pulmonary disease (P < 0.01). CONCLUSIONS: Carbapenems may need to be used more judiciously as first-line empirical therapy for cancer patients with prior pseudomonal infection or chronic obstructive pulmonary disease who require hospitalization, and alternative, antipseudomonal antibiotic regimens may need to be considered, especially in this patient population.

In vitro and ex vivo activities of minocycline and EDTA against microorganisms embedded in biofilm on catheter surfaces.

Minocycline-EDTA (M-EDTA) flush solution has been shown to prevent catheter-related infection and colonization in a rabbit model and in hemodialysis patients. We undertook this study in order to determine the activities of M-EDTA against organisms embedded in fresh biofilm (in vitro) and mature biofilm (ex vivo). For the experiment with the in vitro model, a modified Robbin's device (MRD) was used whereby 25 catheter segments were flushed for 18 h with 10(6) CFU of biofilm-producing Staphylococcus epidermidis, Staphylococcus aureus, and Candida albicans per ml. Subsequently, each of the catheter segments was incubated in one of the following solutions: (i) streptokinase, (ii) heparin, (iii) broth alone, (iv) vancomycin, (v) vancomycin-heparin, (vi) EDTA, (vii) minocycline (high-dose alternating with low-dose), or (viii) M-EDTA (low-dose minocycline alternating with high-dose minocycline were used to study the additive and synergistic activities of M-EDTA). All segments were cultured quantitatively by scrape sonication. For the experiment with the ex vivo model, 54 catheter tip segments removed from patients and colonized with bacterial organisms by roll plate were longitudinally cut into two equal segments and exposed to either saline, heparin, EDTA, or M-EDTA (with high-dose minocycline). Subsequently, all segments were examined by confocal laser electron microscopy. In the in vitro MRD model, M-EDTA (with a low concentration of minocycline) was significantly more effective than any other agent in reducing colonization of S. epidermidis, S. aureus, and C. albicans (P < 0.01). M-EDTA (with a high concentration of minocycline) eradicated all staphylococcal and C. albicans organisms embedded in the biofilm. In the ex vivo model, M-EDTA (with a high concentration of minocycline) reduced bacterial colonization more frequently than EDTA or heparin (P < 0.01). We concluded that M-EDTA is highly active in eradicating microorganisms embedded in fresh and mature biofilm adhering to catheter surfaces.