Macromol Biosci. 2016 May;16(5):647-54.

Quantitative Comparison of the Antimicrobial Efficiency of Leaching versus Nonleaching Polymer Materials.

Bruenke J1, Roschke I2, Agarwal S3, Riemann T4, Greiner A3.

1 QualityLabs BT GmbH, Neumeyerstr. 46 a, 90411, Nuremberg, Germany.

2 Medical Marketing GmbH, Gleueler Straße 237, 50935, Cologne, Germany.

3 Chair of Macromolecular Chemistry II, University of Bayreuth, Universitätsstrasse 30, 95440, Bayreuth, Germany.

4 B. Braun Melsungen AG, Carl-Braun-Straße 1, 34212, Melsungen, Germany.

 

Abstract

New antimicrobial materials will be more and more in the focus for hygienic and clinical disease control. Antimicrobial materials have to be distinguished in leaching and non-leaching materials. For many applications of antimicrobial materials on implants the use of non-leaching materials appears is essential. Therefore, we have investigated quantitatively in-vitro the antimicrobial efficiency of leaching and non-leaching materials in direct comparison on a highly relevant implant of central venous catheters (CVCs) using a well-established called Certika™ test. This test was especially designed to test antimicrobial properties of leachable and non-leachable products. This contribution demonstrates that new developed non-leaching antimicrobial CVCs are equivalent to conventional leaching CVC-systems in their antimicrobial performance against gram-positive and gram-negative bacteria, as well as Candida species. The use of new non-leaching antimicrobial materials as shown here for CVCs represents a different mode of action with the aim to prevent infections also with antibiotic-resistant strains and reduced side-effects.

KEYWORDS:

antimicrobial polymer material; catheters; in vitro test

PMID:26806336; DOI:10.1002/mabi.201500266

 

Supplement: 

Background:

Device-associated infections are a common threat for patients and healthcare workers in healthcare-institutions worldwide, especially when the infections are caused by microorganisms resistant to multiple antibiotics. Therefore, antimicrobial materials are used for numerous applications to create infection-resistant surfaces and to reduce device-associated infections (1;2). Typically materials are equipped with antimicrobials as coatings for polymer or metals devices or as additives for polymer applications. In general, antimicrobial materials as coatings as well as additives can be classified in leaching and non-leaching antimicrobial materials, which is of fundamental importance for a variety of medical and hygiene sensitive applications. Noteworthy, the use of leaching materials is often associated with undesired side effects, such as sensitization, irritation, anaphylaxis or bacterial resistance development. These negative side effects can be obviated by the use of non-leaching surface active materials. Therefore, we have investigated the antimicrobial performance of leaching and non-leaching antimicrobial central venous catheters (CVC) as an example for an important class of medical devices, which are widely used in the management of critical illness and are associated with a significant number of catheter-related blood stream infections (CRBSIs). CRBSIs have been reported to occur in 3% to 8% of all inserted catheters and are ranked as number one of nosocomial bloodstream infection in intensive care units (ICUs) (3;4). CRBSI is associated with increased duration of hospital stay, morbidity and mortality (5-8)

In the hospital setting, most catheter-related infections are derived from the patient´s own skin microflora (9). Coagulase-negative staphylococci, such as Staphylococcus epidermidis and Staphylococcus aureus, are the most frequent cause of catheter-related bloodstream infections in patients, including neonates, children and adults. (Figure 1) (10-12).

 

 

Figure 1: Microorganisms and risk of catheter-related infections

 

Furthermore, the risk of catheter-related bloodstream infections increases over time. The overall incidence of catheter-associated bloodstream infection is 3.7 cases per 1,000 catheter-days, whereas the incidences during the intervals of 1–5, 6–15, and 16–30 days are 2.1, 4.5, and 10.2 cases per 1,000 catheter-days, respectively (Figure 2) (13).

 

 

Figure 2: Risk of catheter-related infections over time

 

The growth of bacteria and the development of a biofilm on the catheter surface is an essential mechanism of the development of catheter-related infections. Inhibition of bacterial growth by antimicrobial catheters would help to prevent surface colonization and improve safety.

 

Method:

Standard antimicrobial test methods have been initially developed for leachable additives, but not for non-leaching products. New test methods are required for the reliable in-vitro evaluation of antimicrobial activity of this new type of non-leaching CVCs. The Certika™ test was especially designed to test antimicrobial properties of leachable and non-leachable products. Proliferation based assays, such as the Certika™ assay (14) are designed to measure the antimicrobial efficacy of both, leaching and non-leaching additives, based on the reproduction of surface bound microorganisms and release of daughter cells over a period of 18 hours after inoculation. Regardless of the antimicrobial mode of action, the implication for bacterial growth on the surface is determined by the release of vital daughter cells, which are responsible for the infection development in the patient’s body. The growth activity of these offspring bacteria is then monitored over a time period of 48 hrs. Antimicrobial activity is determined by the time needed to reach a defined optical density which depends on the number of released cells. In comparison to untreated controls, antimicrobially active materials demonstrate their antimicrobial effect by a delayed (shift to the right) or even inhibited growth. A time difference, the so called “net Onset OD” of 6hrs, represents a reduction of >99.9% (3 log scales) of bacteria on the sample surface, a time difference of 8hrs > 99.99% (4 log scales), respectively.

 

In our investigation we have chosen antimicrobial doted CVCs with leaching and non-leaching materials as well as different classes of antimicrobial additives:

a) Catheters with leaching antimicrobial additives:

–          Ionized silver

–          Rifampicin-Miconazole

–          Silver, sulphadiazine, chlorhexidine

–          Silver, carbon, platinum

b) Catheters with non-leaching antimicrobial additives:

–          Polyhexanide

–          Poly-guanidine

 

We have performed a direct head-to-head comparison of the antimicrobial efficacy of these CVCs with different antimicrobial principles by use of the proliferation-based Certika™ test method against typical CRBSI-related germs, including Gram-positive bacteria (Staphylococcus epidermidis DSM 18857; multi-resistant Staphylococcus aureus MRSA EDCC 5247, Enterococcus faecalis DSM 6134), Gram-negative bacteria (E. coli DSM 682/ATCC 10536, Pseudomonas aeruginosa DSM 939/ATCC 15442 and Klebsiella pneumoniae DSM 6135) and yeast fungus (Candida albicans DSM 5817/10259).

 

Conclusion:

In Certika™ test was performed without a pretreatment in order to test the antimicrobial performance of new CVC systems and after a challenging step in human plasma to simulate in-use conditions after application of the CVC, because blood proteins cover material surfaces and can have an influence on the antimicrobial performance. The results of our investigation demonstrate the equivalency of non-leaching polymer additives in CVC applications compared to the commonly used leaching antimicrobial technologies (figure 3). Noteworthy, the use of non-leaching antimicrobial systems can minimize undesired side effects associated with the leaching systems significantly. The antimicrobial efficacy of non-leaching CVCs was comparable to leachable CVC types against various clinically relevant infection germs, including gram-positive, gram-negative bacteria and yeast. In addition, the effect was not reduced after contact to human plasma, suggesting an antimicrobial efficacy and infection prevention under in-vivo conditions.

The importance of this study is that it is the first evaluation and proof of equivalency of non-leaching polymer additives in CVC applications compared to the commonly used leaching antimicrobial technologies. These results clear the way for future developments of non-leaching materials for medical use.

 

Figure 3:   Head-to-head comparison of antimicrobial efficacy of leaching and non-leaching antimicrobial CVCs against 7 typical CRBSI-associated pathogens. The two tested non-leaching samples, polyhexanide and poly-guanidione, respectively, showed equivalent efficacy compared to leaching samples.

 

References:

[1]       D. Campoccia, L. Montanaro, CR. Aricola, A review of the biomaterials technologies for infection-resistant surfaces. Biomaterials  2013, 34, 8533.

[2]       K. Glinel, P. Thebault, V. Humblot, CM. Pradier, T. Jouenne, Antibacterial surfaces developed from bio-inspired approaches Acta Biomater. 2012, 8(5), 1670.

[3]       D. Fraenkel, C. Rickard, P. Thomas, J. Faoagali, N. George, R. Ware, A prospective, randomized trial of rifampicin-minocycline-coated and silver-platinum-carbon-impregnated central venous catheters. Crit Care Med. 2006, 34, 668.

[4]       D. Frasca, C. Dahyot-Fizelier, O. Mimoz, Prevention of central venous catheter-related infection in the intensive care unit. Critical Care 2010, 14, 212.

[5]       Timsit JF, Dubois Y, Minet C, Bonadona A, Lugosi M, Ara-Somohano C, Hamidfar-Roy R, Schwebel C., New materials and devices for preventing catheter-related infections. Ann Intensive Care 2011, 1, 34.

[6]       RE. Gilbert, M. Harden, Effectiveness of impregnated central venous catheters for catheter related blood stream infection: a systematic review. Curr Opin Infect Dis. 2008, 21, 235.

[7]       Hockenhull JC, Dwan K, Boland A, Smith G, Bagust A, Dündar Y, Gamble C, McLeod C, Walley T, Dickson R., The clinical effectiveness and cost-effectiveness of central venous catheters treated with anti-infective agents in preventing bloodstream infections: a systematic review and economic evaluation. Health Technol Assess. 2008, 12, 1.

[8]       S. Saint, DL. Veenstra, BA. Lipsky, The clinical and economic consequences of nosocomial central venous catheter-related infection: are antimicrobial catheters useful? Infect Control Hosp Epidemiol. 2000, 21, 375.

[9]       Elliott TSJ. The pathogenesis and prevention of intravascular catheter-related infections. In: Hamilton H, Bodenham AR. Central venous catheters. Chichester [u.a.]: Wiley-Blackwell 2009; 206-209

[10]    Ebert T, Smith S, Pancari G, Wu X, Zorman J, Clark D, Cook J, Burns C, Antonello JM, Cope L, Nagy E, Meinke A, McNeely T. Development of a rat central venous catheter model for evaluation of vaccines to prevent Staphylococcus epidermidis and Staphylococcus aureus early biofilms. Hum Vaccin. 2011 Jun;7(6):630-8

[11]    Walz JM, Memtsoudis SG, Heard SO. Prevention of central venous catheter bloodstream infections. J Intensive Care Med. 2010 May-Jun;25(3):131-8

[12]    Mermel LA, Farr BM, Sherertz RJ, Raad II, O’Grady N, Harris JS, Craven DE; Infectious Diseases Society of America; American College of Critical Care Medicine; Society for Healthcare Epidemiology of America. Guidelines for the   management of intravascular catheter-related infections. Clin Infect Dis. 2001 May 1;32(9):1249-72

[13]    McLaws ML, Berry G. Nonuniform risk of bloodstream infection with increasing central venous catheter-days. Infect Control Hosp Epidemiol. 2005 Aug;26(8):715-9

[14]    T. Bechert, P. Steinrücke, Guggenbichler, A new method for screening anti-infective biomaterials. Nat Med. 2000, 6, 1053.

 

 

 

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