In vitro activity and durability of a combination of an antibiofilm and an antibiotic against vascular catheter colonization.

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.

In vitro potency and in vivo efficacy of a novel bis-indole antimicrobial compound in reducing catheter colonization.

Vascular catheters coated with a novel antimicrobial agent (MBX1631) were studied for their ability to protect against bacterial colonization in vitro and in a rabbit model. MBX1631-coated catheters were significantly less likely to become colonized than control catheters both in vitro and in vivo (P < 0.001). Furthermore, device-associated infection was significantly lower in MBX1631-coated catheters than in uncoated ones (P < 0.005).

Bacterial translocation across ePTFE vascular graft surfaces.

OBJECTIVES: Vascular graft infections arise from bacterial colonization of either the external or internal graft surfaces. We assessed whether methicillin-resistant Staphylococcus aureus (MRSA) and Escherichia coli could translocate through pores of ePTFE grafts. METHODS: To assess translocation from the internal to the external surface, we placed 10(5) cfu of bacterial suspension inside ePTFE graft segments and suspended them in sterile broth for 72 h. To assess translocation from the external to the internal surface, we placed sterile broth inside ePTFE segments, and incubated them for 72 h in a bacterial suspension (10(5) cfu/mL). At 72 h, in addition to culturing the sterile broth and bacterial suspensions, the external and internal surfaces were first qualitatively cultured separately and then quantitatively cultured by sonication. RESULTS: At 72 h, the sterile broth remained sterile. The bacterial suspensions yielded 10(7)-10(9) cfu/mL. Graft cultures indicated that colonization of one surface with either organism did not result in bacterial translocation to the other surface. Quantitative bacterial counts of the external vs. internal surfaces were significantly different (p < 0.01). CONCLUSIONS: MRSA and E. coli do not translocate across ePTFE graft surfaces. These in-vitro findings help elucidate the pathogenesis of graft infections and prompt conduction of validation studies in-vivo.

Incubation alone is adequate as a culturing technique for cardiac rhythm management devices.

There exist no standardized methods for culturing cardiac rhythm management devices. To identify the most optimal culturing method, we compared various techniques that comprise vortex, sonication, and incubation or combinations thereof. Incubation alone yielded bacterial colony counts similar to those of other culturing combinations and is the least labor-intensive.

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

Comparative efficacies of telavancin and vancomycin in preventing device-associated colonization and infection by Staphylococcus aureus in rabbits.

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.

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.

Efficacy of combination of N-acetylcysteine, gentamicin, and amphotericin B for prevention of microbial colonization of ventricular assist devices.

We assessed the in vitro antimicrobial activity and the in vivo efficacy of dipping ventricular assist devices in a combination of N-acetylcysteine, gentamicin, and amphotericin B (NAC/G/A). Ventricular assist devices dipped in NAC/G/A exhibited broad-spectrum antimicrobial activity in vitro and were less likely than undipped devices to become colonized with Staphylococcus aureus in a rabbit model.

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.

Association of proton-pump inhibitors with outcomes in Clostridium difficile colitis.

PURPOSE: The role of concurrent use of proton-pump inhibitors (PPIs) in the outcomes of treatment for Clostridium difficile colitis was studied. Methods. The records of inpatients at a large Veterans Affairs medical center in whom C. difficile colitis was diagnosed between June 2004 and July 2005 were retrospectively reviewed. Data collected included patient characteristics at baseline, antibiotic therapy prescribed before and during therapy for C. difficile colitis, concurrent treatment with a PPI, response to therapy for C. difficile colitis, and recurrence of the disease in the 90 days after symptoms resolved. Outcomes of therapy were classified as cures, treatment failures, or disease recurrences. RESULTS: A total of 140 patients (138 men and 2 women) were included in the study. Ninety-seven (69%) of patients received a PPI and 43 (31%) did not. Of patients receiving a PPI, 37 (38%) were cured of C. difficile colitis, 20 (21%) did not respond to therapy, and 40 (41%) had disease recurrence. Among the non-PPI patients, 27 (63%) were cured, 9 (21%) did not respond, and 7 (16%) had recurrence. Patients receiving PPIs were 4.17 times as likely to have recurrence as their counterparts who did not. CONCLUSION: PPI therapy was associated with an increased risk of recurrent C. difficile colitis.

In vivo efficacy of antimicrobial-coated devices.

BACKGROUND: Since device colonization is a prelude to infection, an antimicrobial-coated device that reduces bacterial colonization can potentially protect against infection. The objective of this animal study was to assess the efficacy of a coating with minocycline and rifampin to prevent colonization of a grit-blasted titanium implant and subsequent osteomyelitis. METHODS: Twenty-five rabbits underwent implantation of a titanium-alloy pin, either coated with minocycline and rifampin (thirteen rabbits) or uncoated (twelve rabbits), into the right femoral medullary canal. The implanted devices were inoculated with 500 CFU (colony-forming units) of Staphylococcus aureus prior to wound closure. The rabbits were killed one week later, and the removed device, femoral bone, a specimen obtained by swabbing the track surrounding the device, and blood were cultured. The rates of device colonization, osteomyelitis, and device-related osteomyelitis were compared between the two groups of rabbits. RESULTS: The antimicrobial-coated devices had a significantly lower rate of colonization than the uncoated devices (five of thirteen compared with twelve of twelve, p = 0.0016) and were associated with significantly lower rates of osteomyelitis (six of thirteen compared with twelve of twelve, p = 0.005) and device-related osteomyelitis (five of thirteen compared with twelve of twelve, p = 0.0016). Bacteremia did not develop in any rabbit. CONCLUSIONS: Orthopaedic devices coated with minocycline and rifampin significantly protected against device colonization and infection due to Staphylococcus aureus in this in vivo rabbit model. CLINICAL RELEVANCE: It is possible that orthopaedic devices coated with this unique combination of antimicrobial agents may protect against the development of clinical infection in humans.

Vancomycin-induced elevation of liver enzyme levels.

OBJECTIVE: To report a case of oral vancomycin-induced elevation of liver enzyme levels. CASE SUMMARY: A 57-year-old man with multiple medical conditions requiring systemic antibiotic therapy developed numerous Clostridium difficile-associated enterocolitis episodes. The patient did not respond adequately to oral metronidazole, as evidenced by his continuing diarrhea. He was treated with oral vancomycin on 5 separate occasions (with doses from 125 to 500 mg/day), each of which resulted in significant elevations in alanine aminotransferase (to 371 U/L) and aspartate aminotransferase (to 203 U/L) levels. The elevations resolved on each occasion with discontinuation of vancomycin. DISCUSSION: Vancomycin, a glycopeptide antibiotic, has primary activity against gram-positive bacteria. Oral vancomycin can be used for the treatment of C. difficile-associated enterocolitis in patients who fail to respond to or are intolerant to metronidazole therapy. Oral vancomycin has very poor bioavailability and, as of May 4, 2006, has not been associated with hepatic toxicity. Inflammatory bowel disease processes can result in increased absorption of oral vancomycin. CONCLUSIONS: This is the first reported case of oral vancomycin-induced elevation of hepatic enzyme levels. Use of the Naranjo probability scale indicated that this was a probable adverse drug-associated event.

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 > or = 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.

In vitro activity and in vivo efficacy of antimicrobial-coated vascular grafts.

The serious medical consequences and costly management of infections associated with vascular grafts have prompted an expanding interest in examining the preventive efficacy of antimicrobial-coated vascular grafts. The purpose of antimicrobial coating of vascular grafts is to reduce bacterial colonization of the device and, hopefully, the occurrence of clinical infection. In this study we demonstrated that expanded-polytetrafluoroethylene vascular grafts coated with minocycline and rifampin provide broad-spectrum antimicrobial activity in vitro, as reflected by zones of inhibition, against Staphylococcus epidermidis, S. aureus, Enterococcus faecium, and Pseudomonas aeruginosa. We also showed in a rabbit model that subcutaneously placed minocycline/rifampin-coated vascular grafts have lower rates of staphylococcal device colonization (1/24 = 4% vs. 8/30 = 27%, p = 0.033) and device-related infection (0/24 = 0% vs. 6/30 = 20%, p = 0.028) than uncoated grafts. These promising results encourage the clinical evaluation of vascular grafts coated with minocycline and rifampin.

Activity of antimicrobial-impregnated silicone tissue expanders.

Because bacterial colonization of medical devices may result in clinical infection, it is conceivable that antimicrobial impregnation of tissue expanders may reduce the rate of infection. The objective of this in vitro study was to examine the spectrum, durability, and shelf-life antimicrobial activity of minocycline/rifampin-impregnated silicone tissue expander shells. The impregnated devices exhibited zones of inhibition at baseline against Staphylococcus epidermidis, Staphylococcus aureus, and Escherichia coli. The impregnated devices exhibited strong residual activity against S. epidermidis and S. aureus after suspension in serum at 37 degrees C for 4 weeks. There was no significant decrease in the size of zones of inhibition after storing the impregnated devices at room temperature for 1 year. These results indicate that minocycline/rifampin-impregnated tissue expander shells provide broad-spectrum and durable antimicrobial activity and that the shelf-life antimicrobial activity exceeds 1 year. These findings prompt future exploration of the anti-infective efficacy of these antimicrobial-impregnated devices.

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.

In-vitro and in-vivo activity of antimicrobial-coated prosthetic heart valve sewing cuffs.

BACKGROUND AND AIM OF THE STUDY: Prosthetic valve endocarditis (PVE) is a relatively uncommon but very serious condition. As bacterial colonization of the prosthetic heart valve sewing cuff can be a prelude to the clinical occurrence of PVE, antimicrobial coating of the sewing cuff may be beneficial. The study aims were to examine the antimicrobial activity in vitro and anti-infective efficacy in vivo of prosthetic heart valve sewing cuffs coated with minocycline and rifampin. METHODS: Zones of inhibition by antimicrobial-coated sewing cuffs were assessed in vitro against Staphylococcus epidermidis, S. aureus, Enterococcus faecalis, Pseudomonas aeruginosa and Candida albicans. The ability of subcutaneously implanted devices coated with minocycline and rifampin to resist colonization and infection by P. aeruginosa was also examined in a rabbit model. RESULTS: Antimicrobial-coated sewing cuffs produced zones of inhibition against all tested organisms. Coated devices were significantly less likely than uncoated devices to become colonized (2/24; 8% versus 20/24; 83%; p <0.001) or to cause device-related infection (0/24; 0% versus 18/24; 75%; p <0.001) and device-related abscess (0/24; 0% versus 10/24; 42%; p <0.001) due to P. aeruginosa. CONCLUSION: Prosthetic heart valve sewing cuffs coated with minocycline and rifampin provide broad-spectrum antimicrobial activity in vitro, and are anti-infective in vivo against P. aeruginosa. These results encourage the clinical evaluation of these sewing cuffs.