Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum biofilm eradication concentration (MBEC) and kill kinetics were established for vancomycin, rifampicin, trimethoprim, gentamicin, and ciprofloxacin against the biofilm forming bacteria Staphylococcus epidermidis (ATCC 35984), Staphylococcus aureus (ATCC 29213), Methicillin Resistant Staphylococcus aureus (MRSA) (ATCC 43300), Pseudomonas aeruginosa (PAO1), and Escherichia coli (NCTC 8196). MICs and MBCs were determined via broth microdilution in 96-well plates. MBECs were studied using the Calgary Biofilm Device. Values obtained were used to investigate the kill kinetics of conventional antimicrobials against a range of planktonic and biofilm microorganisms over a period of 24 hours. Planktonic kill kinetics were determined at 4xMIC and biofilm kill kinetics at relative MBECs. Susceptibility of microorganisms varied depending on antibiotic selected and phenotypic form of bacteria. Gram-positive planktonic isolates were extremely susceptible to vancomycin (highest MBC: 7.81？mg？L？1: methicillin sensitive and resistant S. aureus) but no MBEC value was obtained against all biofilm pathogens tested (up to 1000？mg？L？1). Both gentamicin and ciprofloxacin displayed the broadest spectrum of activity with MIC and MBCs in the mg？L？1 range against all planktonic isolates tested and MBEC values obtained against all but S. epidermidis (ATCC 35984) and MRSA (ATCC 43300). 1. Introduction Medical device related infections present an increasing burden on health care systems with concomitant high rates of patient morbidity and mortality [1]. Their increased clinical presentation and associated problems are due mainly to the ability of microorganisms to form resistant biofilms at the biomaterial surface. Biofilms are heterogeneous by nature and contain a subpopulation of dormant persister cells that show tolerance to treatment by standard antimicrobial regimens [2]. In the presence of many standard antibiotics these persister cells reduce metabolic processes and uptake of nutrients and cease multiplying, only to become active again when the antibiotic is at subtherapeutic levels [3]. In order to be clinically successful in the treatment of a medical device infection, the antibiotic’s pharmacokinetic properties, rate of kill, and concentration must be assessed against a spectrum of relevant biofilm forming microorganisms. This study is set out to obtain an indication of the ability of currently prescribed antimicrobials to eradicate both planktonic and biofilm forms of these device
References
[1]
J. P. Guggenbichler, O. Assadian, M. Boeswald, and A. Kramer, “Incidence and clinical implication of nosocomial infections associated with implantable biomaterials—catheters, ventilator-associated pneumonia, urinary tract infections,” GMS Krankenhhyg Interdiszip, vol. 6, no. 1, article 18, 2011.
[2]
K. Lewis, “Multidrug tolerance of biofilms and persister cells,” Current Topics in Microbiology and Immunology, vol. 322, pp. 107–131, 2008.
[3]
K. R. Allison, M. P. Brynildsen, and J. J. Collins, “Heterogeneous bacterial persisters and engineering approaches to eliminate them,” Current Opinion in Microbiology, vol. 14, no. 5, pp. 593–598, 2011.
[4]
M. E. Hulscher, R. P. Grol, and J. W. van der Meer, “Antibiotic prescribing in hospitals: a social and behavioural scientific approach,” The Lancet Infectious Diseases, vol. 10, no. 3, pp. 167–175, 2010.
[5]
L. A. Mermel, M. Allon, E. Bouza, et al., “Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America,” Clinical Infectious Diseases, vol. 49, no. 1, pp. 1–45, 2009.
[6]
M. B. Bestul and H. L. VandenBussche, “Antibiotic lock technique: review of the literature,” Pharmacotherapy, vol. 25, no. 2, pp. 211–227, 2005.
[7]
J. A. Capdevila, A. Segarra, A. M. Planes et al., “Successful treatment of haemodialysis catheter-related sepsis without catheter removal,” Nephrology Dialysis Transplantation, vol. 8, no. 3, pp. 231–234, 1993.
[8]
J.-L. Benoit, G. Carandang, M. Sitrin, and P. M. Arnow, “Intraluminal antibiotic treatment of central venous catheter infections in patients receiving parenteral nutrition at home,” Clinical Infectious Diseases, vol. 21, no. 5, pp. 1286–1288, 1995.
[9]
H. Bagnall-Reeb, “Evidence for the use of the antibiotic lock technique,” Journal of Infusion Nursing, vol. 27, no. 2, pp. 118–122, 2004.
[10]
C. Rotstein, L. Brock, and R. S. Roberts, “The incidence of first Hickman catheter-related infection and predictors of catheter removal in cancer patients,” Infection Control and Hospital Epidemiology, vol. 16, no. 8, pp. 451–458, 1995.
[11]
P. M. Arnow, E. M. Quimosing, and M. Beach, “Consequences of intravascular catheter sepsis,” Clinical Infectious Diseases, vol. 16, no. 6, pp. 778–784, 1993.
[12]
J. Rodriguez-Bano, “Selection of empiric therapy in patients with catheter-related infections,” Clinical Microbiology and Infection, vol. 8, no. 5, pp. 275–281, 2002.
[13]
W. Graninger, O. Assadian, H. Lagler, and M. Ramharter, “The role of glycopeptides in the treatment of intravascular catheter-related infections,” Clinical Microbiology and Infection, vol. 8, no. 5, pp. 310–315, 2002.
[14]
M. P. Ruiz-Valverde, J. R. Barberà, A. Segarra, J. A. Capdevila, A. Evangelista, and L. Piera, “Successful treatment of catheter-related sepsis and extraluminal catheter thrombosis with vancomycin and fraxiparin without catheter removal,” Nephron, vol. 75, no. 3, pp. 354–355, 1997.
[15]
J. M. Boyce, L. A. Mermel, M. J. Zervos et al., “Controlling vancomycin-resistant enterococci,” Infection Control and Hospital Epidemiology, vol. 16, no. 11, pp. 634–637, 1995.
[16]
L. A. Mermel, B. M. Farr, R. J. Sherertz et al., “Guidelines for the management of intravascular catheter-related infections,” Clinical Infectious Diseases, vol. 32, no. 9, pp. 1249–1272, 2001.
[17]
G. Peters and K. Becker, “Epidemiology, control and treatment of methicillin-resistant Staphylococcus aureus,” Drugs, vol. 52, supplement 2, pp. 50–54, 1996.
[18]
H. N. Bentur, A. M. Dalzell, and F. A. I. Riordan, “Central venous catheter infection with Bacillus pumilus in an immunocompetent child: a case report,” Annals of Clinical Microbiology and Antimicrobials, vol. 6, article 12, 2007.
[19]
J. H. Crabtree and N. A. Garcia, “Corynebacterium striatum peritoneal dialysis catheter exit site infection,” Clinical Nephrology, vol. 60, no. 4, pp. 270–274, 2003.
[20]
D. S. Swanson, “Central venous catheter-related infections due to nontuberculous Mycobacterium species,” Pediatric Infectious Disease Journal, vol. 17, no. 12, pp. 1163–1164, 1998.
[21]
D. R. P. Guay, “Nontuberculous mycobacterial infections,” Annals of Pharmacotherapy, vol. 30, no. 7-8, pp. 819–830, 1996.
[22]
M. V. Gill, H. Ly, M. Mueenuddin, P. E. Schoch, and B. A. Cunha, “Intravenous line infection due to Ochrobactrum anthropi (CDC group Vd) in a normal host,” Heart & Lung, vol. 26, no. 4, pp. 335–336, 1997.
[23]
M. J. Ashby, J. E. Neale, S. J. Knott, and I. A. Critchley, “Effect of antibiotics on non-growing planktonic cells and biofilms of Escherichia coli,” Journal of Antimicrobial Chemotherapy, vol. 33, no. 3, pp. 443–452, 1994.
[24]
H. Ishida, Y. Ishida, Y. Kurosaka, T. Otani, K. Sato, and H. Kobayashi, “In vitro and in vivo activities of levofloxacin against biofilm-producing Pseudomonas aeruginosa,” Antimicrobial Agents and Chemotherapy, vol. 42, no. 7, pp. 1641–1645, 1998.
[25]
E. Bouza, A. Burillo, and P. Mu？oz, “Catheter-related infections: diagnosis and intravascular treatment,” Clinical Microbiology and Infection, vol. 8, no. 5, pp. 265–274, 2002.
[26]
S. Stepanovi？, D. Vukovi？, I. Daki？, B. Savi？, and M. ？vabi？-Vlahovi？, “A modified microtiter-plate test for quantification of staphylococcal biofilm formation,” Journal of Microbiological Methods, vol. 40, no. 2, pp. 175–179, 2000.
[27]
G. Laverty, M. McLaughlin, C. Shaw, S. P. Gorman, and B. F. Gilmore, “Antimicrobial activity of short, synthetic cationic lipopeptides,” Chemical Biology & Drug Design, vol. 75, no. 6, pp. 563–569, 2010.
[28]
H. Ceri, M. E. Olson, C. Stremick, R. R. Read, D. Morck, and A. Buret, “The calgary biofilm device: new technology for rapid determination of antibiotic susceptibilities of bacterial biofilms,” Journal of Clinical Microbiology, vol. 37, no. 6, pp. 1771–1776, 1999.
[29]
C. W. Stratton, C. Liu, H. B. Ratner, and L. S. Weeks, “Bactericidal activity of deptomycin (LY146032) compared with those of ciprofloxacin, vancomycin, and ampicillin against enterococci as determined by kill-kinetic studies,” Antimicrobial Agents and Chemotherapy, vol. 31, no. 7, pp. 1014–1016, 1987.
[30]
C. W. Stratton, C. Liu, and L. S. Weeks, “Activity of LY146032 compared with that of methicillin, cefazolin, cefamandole, cefuroxime, ciprofloxacin, and vancomycin against staphylococci as determined by kill-kinetic studies,” Antimicrobial Agents and Chemotherapy, vol. 31, no. 8, pp. 1210–1215, 1987.
[31]
G. A. Pankuch, M. R. Jacobs, and P. C. Appelbaum, “Study of comparative antipneumococcal activities of penicillin G, RP 59500, erythromycin, sparfloxacin, ciprofloxacin, and vancomycin by using time-kill methodology,” Antimicrobial Agents and Chemotherapy, vol. 38, no. 9, pp. 2065–2072, 1994.
[32]
K. Smith, A. Perez, G. Ramage, C. G. Gemmell, and S. Lang, “Comparison of biofilm-associated cell survival following in vitro exposure of meticillin-resistant Staphylococcus aureus biofilms to the antibiotics clindamycin, daptomycin, linezolid, tigecycline and vancomycin,” International Journal of Antimicrobial Agents, vol. 33, no. 4, pp. 374–378, 2009.
[33]
A. A. Miles, S. S. Misra, and J. O. Irwin, “The estimation of the bactericidal power of the blood,” Journal of Hygiene, vol. 38, no. 6, pp. 732–749, 1938.
[34]
P. Wu and D. W. Grainger, “Drug/device combinations for local drug therapies and infection prophylaxis,” Biomaterials, vol. 27, no. 11, pp. 2450–2467, 2006.
[35]
N. Balaban, A. Giacometti, O. Cirioni et al., “Use of the quorum-sensing inhibitor RNAIII-inhibiting peptide to prevent biofilm formation in vivo by drug-resistant Staphylococcus epidermidis,” Journal of Infectious Diseases, vol. 187, no. 4, pp. 625–630, 2003.
[36]
N. P. O'Grady, M. Alexander, E. P. Dellinger et al., “Guidelines for the prevention of intravascular catheter-related infections. Centers for Disease Control and Prevention,” MMWR. Recommendations and Reports, vol. 51, no. 10, pp. 1–29, 2002.
[37]
C. Perry and C. Hall, “Antibiotic resistance: how it arises, the current position and strategies for the future,” Nursing Times, vol. 105, no. 36, pp. 20–23, 2009.
[38]
G. Laverty, S. P. Gorman, and B. F. Gilmore, “The potential of antimicrobial peptides as biocides,” International Journal of Molecular Sciences, vol. 12, no. 10, pp. 6566–6596, 2011.
