Gassan Chaiban

Comparative Activities of Daptomycin, Linezolid, and Tigecycline against Catheter-Related Methicillin-Resistant Staphylococcus Bacteremic Isolates Embedded in Biofilm

ABSTRACT 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.

In Vitro and Ex Vivo Activities of Minocycline and EDTA against Microorganisms Embedded in Biofilm on Catheter Surfaces

ABSTRACT 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 106 CFU of biofilm-producing Staphylococcus epidermidis, Staphyloccocus 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.

Optimal Antimicrobial Catheter Lock Solution, Using Different Combinations of Minocycline, EDTA, and 25-Percent Ethanol, Rapidly Eradicates Organisms Embedded in Biofilm

ABSTRACT 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°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 In Vitro Efficacies and Antimicrobial Durabilities of Novel Antimicrobial Central Venous Catheters

ABSTRACT 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.

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

ABSTRACT 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.

Clinical experience with minocycline and rifampin-impregnated central venous catheters in bone marrow transplantation recipients: efficacy and low risk of developing staphylococcal resistance.

In this retrospective evaluation of the 4-year clinical use of minocycline and rifampin-impregnated catheters in bone marrow transplantation (BMT) patients, we report low risk of development of staphylococcal resistance to the antibiotics coating the catheters and efficacy in preventing primary staphylococcal bloodstream infections.

Clinical-Use-Associated Decrease in Susceptibility of Vancomycin-Resistant Enterococcus faecium to Linezolid: a Comparison with Quinupristin-Dalfopristin

ABSTRACT 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.

Erratum: Comparative in vitro efficacies and antimicrobial durabilities of novel antimicrobial central venous catheters (Antimicrobial Agents and Chemotherapy (2006) 50, 10 (3283-3288))

Volume 50, no. 10, p. 3283–3288, 2006. Page 3285, column 2, line 55: The sentence should read, “Although the antibiotic-coated M/R-CVCs have been shown through a number of prospective randomized clinical trials to be highly efficacious in preventing CR-BSI in short-term and long-term CVCs (4, 8, 9, 12, 32), there are several concerns associated with their use.” Page 3286, column 2, line 5: The sentence should read, “Although several other studies have demonstrated that such a possibility is low (5, 12, 25), the use of an antiseptic catheter coating, especially one which contains two separate antiseptics, is probably associated with less risk of emergence of organisms that could be resistant to those antibiotics that are commonly used therapeutically.” Page 3287: The Acknowledgments should include the following sentence. “Hend Hanna, Gassan Chaiban, and Issam Raad are coinventors of the technology related to gendine-coated central venous catheters. This technology is the property of the University of Texas M. D. Anderson Cancer Center.”