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Scientific Articles   |    
In Vivo Efficacy of Antimicrobial-Coated Devices
Rabih O. Darouiche, MD1; Mohammad D. Mansouri, BS2; Devin Zakarevicz, PA3; Atef AlSharif, MD2; Glenn C. Landon, MD3
1 Center for Prostheses Infection, Baylor College of Medicine, 1333 Moursund Avenue, Suite A221, Houston, TX 77030. E-mail address: rdarouiche@aol.com
2 Spinal Cord Injury Laboratory, Michael E. DeBakey Veterans Affairs Medical Center, Room 178, 2002 Holcombe Boulevard., Houston, TX 77030. E-mail address for M.D. Mansouri: mansouri@bcm.tmc.edu. E-mail address for A. AlSharif: alsharif@bcm.tmc.edu
3 Section of Orthopedic Surgery, Kelsey-Seybold Clinic, 2727 West Holcombe Boulevard, Houston, TX 77025. E-mail address for D. Zakarevicz: dmzakarevicz@kelsey-seybold.com. E-mail address for G.C. Landon: gclandon@kelsey-seybold.com
View Disclosures and Other Information
Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from Biomet Orthopedics, Inc, and funding or grants of less than $10,000 from the Department of Veterans Affairs. In addition, one or more of the authors or a member of his or her immediate family received, in any one year, payments or other benefits of less than $10,000 or a commitment or agreement to provide such benefits from a commercial entity (Biomet Orthopedics, Inc.). Also, a commercial entity (Biomet Orthopedics, Inc.) paid or directed in any one year, or agreed to pay or direct, benefits in excess of $10,000 to a research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.
Investigation performed at the Center for Prostheses Infection, Baylor College of Medicine; the Section of Orthopedic Surgery, Kelsey-Seybold Clinic; and Michael E. DeBakey Veterans Affairs Medical Center, Houston, Texas

The Journal of Bone and Joint Surgery, Incorporated
J Bone Joint Surg Am, 2007 Apr 01;89(4):792-797. doi: 10.2106/JBJS.F.00414
5 Recommendations (Recommend) | 3 Comments | Saved by 3 Users Save Case

Abstract

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.

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    References

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    These activities have been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of the American Academy of Orthopaedic Surgeons and The Journal of Bone and Joint Surgery, Inc. The American Academy of Orthopaedic Surgeons is accredited by the ACCME to provide continuing medical education for physicians.
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    Rabih O Darouiche, M.D.
    Posted on March 16, 2008
    Dr. Darouiche responds to Dr. Neogi et al.
    Baylor College of Medicine, Houston, TX

    I appreciate the concern by Neogi and colleagues(1) for the potential development of rifampin resistance among agents of tuberculosis in scenarios where systemic antituberculous medications are suboptimally used. However, this potential concern does not necessarily imply that rifampin resistance is likley to occur among mycobacterial or bacterial organisms, including staphylococci, in patients who receive devices coated with the optimal combination of rifampin and minocycline. In fact, several clinical studies have shown no evidence for development of rifampin resistance among bacterial organisms, including staphylococci, in patients who receive rifampin-minocycline coated vascular catheters (2-4).

    The following two factors, among others, help explain why the liklihood of developing rifampin resistance among mycobacterial or bacterial organisms is very low in patients who receive rifampin-minocycline coated orthopedic devices. First, unlike with systemic therapy, these orthopedic devices coated with very small amounts of rifampin and minocycline do not result in systemic levels of either coating agent and, therefore, there is not much concern that rifampin molecules will predispose to evolution of resistance at distant bodily sites, including pulmonary tissues where mycobacteria may exist. Secondly, since rifampin and minocycline possess different mechanisms of antimicrobial activity (rifampin inhibits DNA-dependent RNA polymersae, whereas minocycline inhibits protein synthesis), it is very unlikley that organisms will develop concomitant resistance to rifampin and minocycline.

    Since orthopedic devices coated with the combination of rifampin and minocycline retards the presence of bacteria within the layer of biofilm that acts as a reservoir for resistant organisms, this coating approach may, in fact, have a positive impact on infection control.

    References:

    1. Darouiche RO, Mansouri MD, Zakarevicz D, AlSharif A, Landon GC. In Vivo Efficacy of Antimicrobial-Coated Devices. J Bone Joint Surg Am. 2007;89:792-797.

    2. Raad I, Darouiche R, Dupuis J, et al. Central venous catheters coated with minocycline and rifampin for the prevention of catheter- related colonization and bloodstream infections: a randomized, double- blind trial. Ann Intern Med. 1997;127:267-274.

    3. Darouiche RO, Raad II, Heard SO, et al. A comparison of two antimicrobial-impregnated central venous catheters. N Engl J Med. 1999;340:1-8.

    4. Chatzinikolaou I, Hanna H, Graviss L, et al. Clinical experience with minocycline and rifampin-impregnated central venous catheters in bone marrow transplantation recipients: efficacy and low risk of developing staphylococcal resistance. Infect Control Hosp Epidemiol. 2003;24:961- 965.

    Devdatta S Neogi, MS(Ortho), DNB(Orth Surg)
    Posted on February 21, 2008
    Rifampin-minocycline Coated Orthopaedic Implants - Is There a Need for Caution?
    Department of Orthopaedics, All India Institute of Medical Sciences, New Delhi, INDIA

    To The Editor:

    We read with great interest the article “In Vivo Efficacy of Antimicrobial-Coated Devices”(1) and acknowledge the excellent experimental work.

    With approximately 9 million people developing active tuberculosis (TB) every year and 1.7 million deaths resulting from TB infection annually, TB is far from under control and is a major public health problem in Asia and Africa(2). The increasing spread of multi-drug resistant TB (MDR-TB) and the recalcitrant nature of persistent infections pose additional challenges to treatment with currently available anti-TB drugs(2). The majority of people in a developing country like India are routinely exposed to mycobacterium tuberculosis (MTB) and the prevalence of MTB infection in all age groups in India is around 40%(3).

    The antibiotic levels on the implant used in study are low(1);the coated human implant, if made, would increase rifampin levels proportionally. Our concern is that the suboptimal use of antituberculous medications creates a selective milieu in the host’s tissues where the initially low numbers of drug-resistant mutants are able to replicate, eventually replacing the initially drug-susceptible MTB population(4). Though this study(1) has used a companion drug to prevent development of resistance to staphylococcus aureus, there is no companion drug against MTB, thus increasing the chance of selecting resistant mutants. A study(5) has also shown emergence of rifampin resistance to MRSA in tuberculosis wards and, hence, the question arises why this can't it happen the reverse way round.

    Rifampin-minocycline is a useful drug in the management of implant related infection,but a word of caution must be expressed regarding its use especially in developing countries. The possibilities of adding on to the burden of MDR – TB in such a scenario would seriously set back the public health programme of TB control which is a greater public health concern and where rifampin is a very important drug.

    The authors did not receive any outside funding or grants in support of their research for or preparation of this work. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

    References:

    1. Darouiche RO, Mansouri MD, Zakarevicz D, AlSharif A, Landon GC. In Vivo Efficacy of Antimicrobial-Coated Devices. J Bone Joint Surg Am. 2007;89:792-797.

    2. Medicines for tuberculosis. WHO Drug Information. Vol 20, No. 4, 2006. Available at http://www.who.int/druginformation/vol20num4_2006/DI20-4.pdf. Accessed on 8th Feb 2008.

    3. Chakraborty AK. Epidemiology of tuberculosis: Current status in India. Indian J Med Res. 2004;120:248-276.

    4. David HL. Probability of distribution of drug-resistant mutants in unselected populations of Mycobacterium tuberculosis. Appl Micro. 1970;20:810–814.

    5. Sekiguchi J, Fujino T, Araake M, Toyota E, Kudo K, Saruta K, Yoshikura H, Kuratsuji T, Kirikae T. Emergence of rifampicin resistance in methicillin-resistant Staphylococcus aureus in tuberculosis wards. J Infect Chemother. 2006;12:47-50.

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