Mohammad D. Mansouri

Antimicrobial and antibiofilm efficacy of triclosan and DispersinB combination.

OBJECTIVES The objectives of this study were to examine: (i) synergy of the combination of triclosan and DispersinB (DspB); (ii) in vitro efficacy and durability of triclosan + DspB-coated vascular catheters; and (iii) in vivo efficacy of triclosan + DspB-coated catheters compared with chlorhexidine-silver sulfadiazine (CH-SS)-coated and uncoated (control) vascular catheters in preventing colonization by Staphylococcus aureus. METHODS We investigated the potential synergistic antimicrobial and antibiofilm activity of triclosan and DspB by biofilm assays. The in vitro antimicrobial efficacy of triclosan + DspB-coated catheters was determined by microbial colonization assays. Antimicrobial durability of the coated catheters was tested by soaking segments in bovine serum for 7 days and determining antimicrobial activity, and by a serial plate transfer method. The in vivo efficacy of triclosan + DspB-coated catheters compared with CH-SS-coated and uncoated catheters was assessed by subcutaneous implantation of segments in a rabbit model of S. aureus infection. RESULTS The combination of triclosan and DspB showed synergistic antimicrobial and antibiofilm activity against S. aureus, Staphylococcus epidermidis and Escherichia coli, significantly reduced bacterial colonization (P < 0.05) and generally demonstrated a prolonged superior antimicrobial activity against clinical pathogens compared with CH-SS-coated catheters. Triclosan + DspB-coated and CH-SS-coated catheters exhibited equal in vivo efficacy (P <or= 0.05) in reducing colonization by S. aureus compared with uncoated catheters. CONCLUSIONS Catheters coated with the triclosan + DspB combination showed synergistic, broad-spectrum and durable antimicrobial activity. Furthermore, the in vivo efficacy of catheters coated with this unique antimicrobial/antibiofilm composition prompts clinical evaluation of such an innovative approach.

Comparison of Antimicrobial Impregnation With Tunneling of Long-term Central Venous Catheters: A Randomized Controlled Trial

Objective:We sought to compare the impact of antimicrobial impregnation to that of tunneling of long-term central venous catheters on the rates of catheter colonization and catheter-related bloodstream infection. Summary Background Data:Tunneling of catheters constitutes a standard of care for preventing infections associated with long-term vascular access. Although antimicrobial coating of short-term central venous catheters has been demonstrated to protect against catheter-related bloodstream infection, the applicability of this preventive approach to long-term vascular access has not been established. Methods:A prospective, randomized clinical trial in 7 university-affiliated hospitals of adult patients who required a vascular access for ≥2 weeks. Patients were randomized to receive a silicone central venous catheter that was either impregnated with minocycline and rifampin or tunneled. The occurrence of catheter colonization and catheter-related bloodstream infection was determined. Results:Of a total of 351 inserted catheters, 346 (186 antimicrobial-impregnated and 160 tunneled) were analyzed for catheter-related bloodstream infection. Clinical characteristics were comparable in the 2 study groups, but the antimicrobial-impregnated catheters remained in place for a shorter period of time (mean, 30.2 versus 43.8 days). Antimicrobial-impregnated catheters were as likely to be colonized as tunneled catheters (7.9 versus 6.3 per 1000 catheter-days). Bloodstream infection was 4 times less likely to originate from antimicrobial-impregnated than from tunneled catheters (0.36 versus 1.43 per 1000 catheter-days). Conclusions:Antimicrobial impregnation of long-term central venous catheters may help obviate the need for tunneling of catheters.

Anti-infective Efficacy of Antiseptic-coated Intramedullary Nails*†

The coating of medical devices with antimicrobial agents has recently emerged as a potentially effective method for the prevention of device-related infections. We examined the anti-infective efficacy of intramedullary nails coated with an antiseptic combination of chlorhexidine and chloroxylenol in a rabbit model of device-related infection after fixation of an open tibial fracture. The rabbits were randomized to receive 2.8-by-100-millimeter stainless-steel tibial intramedullary nails that either were uncoated or were coated with antiseptic. After administration of anesthesia and preoperative antibiotic prophylaxis, a tibial fracture was created and then reduced with insertion of the intramedullary nail. A bacterial inoculum of 106 colony-forming units of Staphylococcus aureus was injected into the intramedullary canal, and the wound was sutured. Radiographs of the tibiae were made postoperatively, and the rabbits were monitored daily. They were killed at six weeks, or earlier if there was dehiscence of the wound, the fracture became grossly unstable, or the rabbit failed to thrive. The use of the antiseptic-coated nails was associated with a significantly lower rate of device-related osteomyelitis (two of twenty-two; 9 per cent) than the use of the uncoated nails (thirteen of twenty-one; 62 per cent) (p = 0.0003). The radiographic and histopathological findings were generally similar in the two groups of rabbits. Antiseptic agents were not detected in serum. The results suggest that antiseptic-coated fracture-fixation devices provide significant local protection against Staphylococcus aureus, which is the most common cause of infections related to orthopaedic devices.

Efficacy of combination of chlorhexidine and protamine sulphate against device-associated pathogens

OBJECTIVES The objectives of this study were to examine: (i) the potential in vitro synergy of combining protamine sulphate (PS) with chlorhexidine (CHX); (ii) the in vitro spectrum and durability of antimicrobial activity of CHX + PS-coated catheters; and (iii) the in vivo efficacy of CHX + PS-coated catheters in comparison with silver-hydrogel-coated and uncoated catheters. METHODS The potential synergistic antimicrobial and antibiofilm activities of CHX and PS were investigated in vitro by the MIC and biofilm assays. The spectrum and durability of antimicrobial activity of CHX + PS-coated catheters were studied in vitro by using a serial plate transfer method. The in vivo efficacy of CHX + PS-coated catheters was assessed in a rabbit model against Escherichia coli. RESULTS In vitro studies showed that the combination of CHX + PS has a synergistic inhibitory effect on E. coli and provides a significant synergistic antibiofilm and antimicrobial activity against E. coli, Pseudomonas aeruginosa and Staphylococcus epidermidis. Furthermore, catheters coated with CHX + PS provided a broad-spectrum and enduring in vitro antimicrobial activity over a 10 day period. The in vivo efficacy study demonstrated that subcutaneously implanted CHX + PS-coated catheters in rabbits are significantly less likely to become colonized (2/28 = 7%) than either silver-hydrogel-coated (25/28 = 89%; P < 0.001) or uncoated catheters (18/28 = 64%; P < 0.001) by E. coli. CONCLUSIONS The synergistic, broad-spectrum and durable in vitro activity of the CHX + PS combination and the robust in vivo efficacy of catheters coated with this unique composition encourage clinical evaluation of this innovative approach.

Antimicrobial activity of antiseptic-coated orthopaedic devices

Antimicrobial coating of medical devices, including fracture fixation devices, has evolved as a potentially effective method for preventing device-related infections. We examined the in vitro antimicrobial activity of titanium cylinders coated with the antiseptic combination of chlorhexidine and chloroxylenol. The coated devices provided zones of inhibition against Staphylococcus epidermidis, S. aureus, Pseudomonas aeruginosa, Escherichia coli and Candida albicans, at baseline and up to 8 weeks after incubation of the coated cylinders in human serum at 37 degrees C. This durable antimicrobial activity was attributed to the relatively slow leaching of chlorhexidine and chloroxylenol from the coated cylinders as measured by high-performance liquid chromatography. These results suggest that antiseptic-coated orthopaedic devices may provide broad-spectrum and durable antimicrobial protection against device-related infection.

In vivo efficacy of antimicrobe-impregnated saline-filled silicone implants

Bacterial colonization of mammary implants is a prelude to clinical infection and has been implicated in the etiology of capsular contracture. Antimicrobial impregnation of a variety of medical devices with the combination of minocycline and rifampin has recently emerged as a potentially effective method for preventing device colonization and device-related infection. The objective of this animal study was to examine in vivo the antimicrobial efficacy of minocycline/rifampin-impregnated, saline-filled silicone implants. A rabbit model of Staphylococcus aureus colonization and infection of subcutaneously placed implants was used. A total of 48 saline-filled silicone implants (24 antimicrobe-impregnated and 24 control unimpregnated implants) were suspended in a 106 colony-forming units/ml bacterial suspension of S. aureus for 30 minutes at room temperature, allowed to dry for 60 minutes, and then implanted subcutaneously in the back of 12 rabbits (two antimicrobe-impregnated and two control implants were placed in each rabbit). Rabbits were monitored daily, then killed either at 2 weeks (10 rabbits) or at 4 weeks (two rabbits) and cultured. The antimicrobe-impregnated implants were 12 times less likely to be colonized than control unimpregnated implants (two of 24 versus 23 of 24; p < 0.001), and they were a significantly less likely cause of implant-related infection (0 of 24 versus 22 of 24; p < 0.001) and implant-related abscess (0 of 24 versus 21 of 24; p < 0.001) than control implants. The minocycline/rifampin-impregnated implants routinely demonstrated zones of inhibition against S. aureus at the time of explantation. These results indicate that minocycline/rifampin-impregnated implants can significantly decrease the rate of bacterial colonization, implant-related infection, and implant-related abscess. Antimicrobe-impregnated implants also have the potential of reducing the likelihood of capsular contracture.

Efficacy of antimicrobial-impregnated silicone sections from penile implants in preventing device colonization in an animal model☆

OBJECTIVES To assess, in an animal study, the efficacy of minocycline/rifampin-impregnated silicone sections of pump bulbs from penile implants in preventing device colonization by Staphylococcus aureus. Infection constitutes a very serious complication of penile implants. METHODS Minocycline/rifampin-impregnated and control silicone pump bulb sections from penile implants were each inoculated with about 10(3) to 10(4) colony-forming units of S. aureus. After 8 hours of incubation with bacteria at room temperature, the test devices were allowed to dry for 30 minutes, and then subcutaneously implanted in the backs of rabbits. Eleven rabbits each received a total of six devices. The wounds were sutured, and the rabbits were monitored daily, then killed at 2 days after surgery. In vitro zones of inhibition against S. aureus by the minocycline/rifampin-impregnated and control devices were also determined. RESULTS All of the six tested antimicrobial-impregnated devices but none of the control devices produced zones of inhibition in vitro against S. aureus (mean zone of inhibition by antimicrobial-impregnated devices of 23 mm). The antimicrobial-impregnated devices retrieved from rabbits were sixfold less likely than were the control devices to be colonized with S. aureus (2 [6%] of 33 versus 11 [33%] of 33, respectively; P = 0.011). CONCLUSIONS The results of this animal study indicate that minocycline/rifampin-impregnated pump bulb sections from penile implants provide antimicrobial activity in vitro against S. aureus and protect against staphylococcal colonization of devices implanted for 2 days in animals.

Comparative Assessment of Antimicrobial Activities of Antibiotic-Treated Penile Prostheses

BACKGROUND Although infections associated with penile implants are relatively infrequent, they result in serious medical consequences. Because treatment of these infections usually requires removal of the infected penile implant, prevention of infection is crucial. Since bacterial colonization of the implant is a prelude to clinical infection, antimicrobial modification of the devices may inhibit device colonization and subsequent infection. OBJECTIVE We compared the spectrum and durability, both in vitro and in vivo, of two antibiotic-treated penile prostheses: InhibiZone implants pre-impregnated with minocycline and rifampin (M/R) and Titan implants dipped in vancomycin. DESIGN, SETTING, AND PARTICIPANTS 1×1-cm cylinder segments of (1) control untreated, (2) M/R-impregnated, and (3) vancomycin-dipped implants were studied. Baseline zones of inhibition (ZI) were determined against clinical isolates, including methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant S. epidermidis (MRSE), vancomycin-resistant Enterococcus (VRE), and Escherichia coli. In addition, ZI against methicillin-susceptible S. aureus were compared both in vitro after being washed in a flow chamber and after subcutaneous implantation in rabbits for 1, 2, 7, and 14 d. MEASUREMENTS ZI were measured as the diameter of the clear zone around each test device minus the external diameter of the device. RESULTS AND LIMITATIONS Implants pre-impregnated with M/R displayed a broader spectrum of antimicrobial activity than vancomycin-dipped implants against both gram-positive and -negative bacteria. The M/R-impregnated devices also yielded significantly larger zones of inhibition against S. aureus than vancomycin-dipped implants, both in vitro (p<0.003) and in vivo throughout the 14-d period of device implantation in rabbits (p≤0.03). CONCLUSIONS Penile prostheses impregnated with M/R have a broader spectrum in vitro and a more durable antimicrobial activity in vitro and in an animal model than implants dipped in vancomycin. Therefore, along with being a more practical model for incorporating antimicrobials onto the device, the use of implants pre-impregnated with M/R may help reduce the incidence of penile implant infection.

Comparative Efficacies of Telavancin and Vancomycin in Preventing Device-Associated Colonization and Infection by Staphylococcus aureus in Rabbits

ABSTRACT Telavancin is an investigational lipoglycopeptide antibiotic that is active against gram-positive pathogens. In an in vivo rabbit model, subtherapeutic (15-mg/kg) and therapeutic (30- or 45-mg/kg) doses of telavancin were demonstrated to be noninferior and superior to vancomycin (20 mg/kg), respectively, for preventing subcutaneous implant colonization and infection by Staphylococcus aureus.

In Vitro Activity and Durability of a Combination of an Antibiofilm and an Antibiotic against Vascular Catheter Colonization

ABSTRACT Catheter-associated infections can cause severe complications and even death. Effective antimicrobial modification of catheters that can prevent device colonization has the potential of preventing clinical infection. We studied in vitro the antimicrobial activities of central venous catheters impregnated with N-acetylcysteine (NAC), an antibiofilm agent, and a broad-spectrum antibiotic against a range of important clinical pathogens. NAC-levofloxacin-impregnated (NACLEV) catheters were also evaluated for their antiadherence activity. NACLEV catheters produced the most active and durable antimicrobial effect against both Gram-positive and Gram-negative isolates and significantly reduced colonization (P < 0.0001) by all tested pathogens compared to control catheters. These in vitro results suggest that this antimicrobial combination can potentially be used to combat catheter colonization and catheter-associated infection.