Prevention of Biofilm Colonization by Gram-Negative Bacteria on Minocycline-Rifampin-Impregnated Catheters Sequentially Coated with Chlorhexidine

Abstract

Resistant Gram-negative bacteria are increasing central-line-associated bloodstream infection threats. To better combat this, chlorhexidine (CHX) was added to minocycline-rifampin (M/R) catheters. The in vitro antimicrobial activity of CHX-M/R catheters against multidrug resistant, Gram-negative Acinetobacter baumannii, Enterobacter cloacae, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Stenotrophomonas maltophilia was tested. M/R and CHX-silver sulfadiazine (CHX/ SS) catheters were used as comparators. The novel CHX-M/R catheters were significantly more effective (P < 0.0001) than CHX/SS or M/R catheters in preventing biofilm colonization and showed better antimicrobial durability. Central venous catheters (CVCs) are essential medical devices in the care of critically ill and cancer patients. Despite their significant usefulness, CVCs are also the source of 87% of the bloodstream infections that occur in intensive care units (1), with attributable mortality rates ranging from 13 to 25% and increases in hospital stays ranging from 7 to 12 days (2, 3). In the United States, more than 5 million CVCs are inserted annually (4, 5) and are responsible for 250,000 to 400,000 annual cases of health careassociated bloodstream infections (6, 7). Hence, central-line-associated bloodstream infections (CLABSIs) are the most common and serious complications associated with indwelling CVCs (5).CVCs coated with antimicrobial agents have been proven to considerably reduce the risk of CLABSIs, and the use of antimicrobial CVCs has become a standard of care (8, 9). Two antimicrobial CVCs, minocycline-rifampin (M/R) and chlorhexidinesilver sulfadiazine (CHX/SS), were clinically proven to reduce CLABSIs at a time when skin-derived, Gram-positive bacteria were the most significant pathogens and were given CDC category 1A recommendations in the most recent guidelines for the prevention of intravascular-catheter-related infections (8-10). However, significant advances in skin antisepsis and sterile barrier precautions have shifted the epidemiologic threat increasingly to Gram-negative bacteria (11). The in vitro efficacy of M/R and CHX/SS against emerging Gram-negative pathogens is limited. In this report, we describe the development of a chlorhexidine-minocycline-rifampin (CHX-M/R) CVC. We compared the antimicrobial adherence activity and durability of M/R, CHX/SS, and CHX-M/R CVCs in a well-established in vitro model for the preventing biofilm colonization by multidrug-resistant clinical isolates of A. baumannii, E. cloacae, E. coli, K. pneumoniae, P. aeruginosa, and S. maltophilia. These organisms were found to contribute to the majority of Gram-negative CLABSIs in the United States from 2009 to 2010 (12). Developing an antimicrobial catheter with broad-spectrum antifungal and antibacterial activity that includes resistant Gram-negative bacteria is of paramount importance because of the mortality rates associated with Gram-negative bacteremia, which may exceed 40% (13,14).CHX-M/R was prepared by a proprietary ...

Acinetobacter baumannii biofilm resistance mechanisms and prevention and control of progress

“…Flos lonicerae, Wuwei xiaodu pulvis, Shuanghuanglian, Chinese gallnut extract and ginseng monomer [40][41][42] have the effect of inhibiting or destroying the biofilm. The bacteriophage AB7-IBB1, AB7-IBB2 and OligoG [27,[43][44][45] can promote dissociation and release of biofilm. Nanoparticles break the existing mechanism of resistance, including the reduction of drug absorption and the inhibition of the formation of Acinetobacter baumannii biofilm.…”

“…Application of new materials such as hydrophilic polymer materials and catheter surface coated with silver ions, chlorhexidine, [27] titanium dioxide nanoparticles, hydrogel-coated ionic fluoroplastics, etc., can inhibit the value of Acinetobacter baumannii and prevente the formation of biofilms. [28] The monoclonal antibody generated from the EPS of Acinetobacter baumannii can destroy EPS.…”

Development of Gendine-Coated Cannula for Continuous Subcutaneous Insulin Infusion for Extended Use

“…Uncoated control and gendine-coated cannulas were tested for the inhibition of biofilm formation using a biofilm colonization model, with a slight modification (14)(15)(16)(17). Both ends of 1-cm segments of the cannulas were heat-sealed, as the lumen was not coated to test antimicrobial efficacy.…”

“…Each weekly challenge tested cannula segments that had been removed from the agarose gel, which had not been exposed to pathogens, and fresh pathogens that had no previous exposure to gendine. After challenge, the segments were washed and processed as described before in the biofilm colonization model (14)(15)(16)(17).…”

Minocycline Inhibits <i>Candida albicans</i> Budded-to-Hyphal-Form Transition and Biofilm Formation

“…Minocycline, a derivative of tetracycline, is a broad-spectrum antimicrobial agent inhibiting bacterial protein synthesis; the drug has been used for coating catheters in an effort to prevent device-related infections (9).…”