Generic placeholder image

Anti-Infective Agents


ISSN (Print): 2211-3525
ISSN (Online): 2211-3533

Research Article

Assessment of Efficacy and Safety of Clindamycin Against Methicillin- Resistant Staphylococcus aureus (MRSA) Infected Subcutaneous Abscess Model

Author(s): Lalitha Vivekanandan*, Hajasherief Sheik, Sengottuvelu Singaravel and Sivakumar Thangavel

Volume 18, Issue 2, 2020

Page: [144 - 151] Pages: 8

DOI: 10.2174/2211352517666190301142421


Background: Methicillin-resistant Staphylococcus aureus (MRSA) causes infection in the wound leading to life-threatening bacteriemia. It causes recalcitrant infections because of being resistant to various antibiotics. The recent studies reported clindamycin to be effective against MRSA rather than inducible clindamycin resistance and decrease the incidence of new infections after clindamycin treatment. The study focused on assessing the efficacy and safety of clindamycin against MRSA infected rats.

Methods: The rats become neutropenic by intraperitoneal administration of cyclophosphamide at a dose of 150 mg/kg and 100 mg/kg for 4 days and 5th day respectively. The neutropenic rats were infected with MRSA by subcutaneous administration of 106 CFU/ml of MRSA. The 3 groups of rats such as Normal, MRSA infected, MRSA infected rats that were administered clindamycin orally at a dose of 90 mg/kg/ thrice daily for 14 days were used in the study. The abscess size, weight, and bacterial load were measured at the end of the study. The blood and liver samples were collected for biochemical analysis and histopathological evaluation.

Results: The MRSA was confirmed by Polymerase Chain Reaction (PCR) method. The clindamycin minimum inhibitory concentration was 0.125 - 0.5 μg/ml. The MRSA showed negative D test for clindamycin indicating the absence of inducible clindamycin resistance. The decreased abscess size, weight, bacterial count, Intestinal Alkaline Phosphatase (IAP), weight loss, alteration in hematological parameters, mild changes in cholesterol, ALT and liver histology, no significant (P > 0.05) change in triglycerides, AST, ALP, bilirubin, lactate, urea, and creatinine were seen in clindamycin treated MRSA infected rats. The MRSA infected clindamycin treated rats showed mild irritation and diarrhea.

Conclusion: Our study concludes that the clindamycin showed better anti- MRSA activity and tolerable adverse effects such as anemia, weight loss, and mild irritation after oral treatment, but the intestinal dysbiosis is a severe adverse effect and causes diarrhea.

Keywords: Clindamycin, Methicillin-resistant Staphylococcus aureus, abscess, IAP, neutropenia, diarrhea.

Graphical Abstract
Garau, J.; Bouza, E.; Chastre, J.; Gudiol, F.; Harbarth, S. Management of methicillin-resistant Staphylococcus aureus infections. Clin. Microbiol. Infect., 2009, 15(2), 125-136.
[] [PMID: 19291144]
Stryjewski, M.E.; Chambers, H.F. Skin and soft-tissue infections caused by community-acquired methicillin-resistant Staphylococcus aureus. Clin. Infect. Dis., 2008, 46(5)(Suppl. 5), S368-S377.
[] [PMID: 18462092]
LaPlante, K.L.; Leonard, S.N.; Andes, D.R.; Craig, W.A.; Rybak, M.J. Activities of clindamycin, daptomycin, doxycycline, linezolid, trimethoprim-sulfamethoxazole, and vancomycin against community-associated methicillin-resistant Staphylococcus aureus with inducible clindamycin resistance in murine thigh infection and in vitro pharmacodynamic models. Antimicrob. Agents Chemother., 2008, 52(6), 2156-2162.
[] [PMID: 18411321]
Falagas, M.E.; Gorbach, S.L. Clindamycin and metronidazole. Med. Clin. North Am., 1995, 79(4), 845-867.
[] [PMID: 7791427]
Stevens, D.L.; Bisno, A.L.; Chambers, H.F.; Everett, E.D.; Dellinger, P.; Goldstein, E.J.C.; Gorbach, S.L.; Hirschmann, J.V.; Kaplan, E.L.; Montoya, J.G.; Wade, J.C. Infectious Diseases Society of America.Practice guidelines for the diagnosis and management of skin and soft-tissue infections. Clin. Infect. Dis., 2005, 41(10), 1373-1406.
[] [PMID: 16231249]
Smieja, M. Current indications for the use of clindamycin: A critical review. Can. J. Infect. Dis., 1998, 9(1), 22-28.
[] [PMID: 22346533]
Russell, E.L.; Michael, E.K. Update on clindamycin: New pharmacokinetic and pharmacodynamic data. Infect. Med., 1998, 15(10), 726-731.
Levison, M.E.; Levison, J.H. Pharmacokinetics and pharmacodynamics of antibacterial agents. Infect. Dis. Clin. North Am., 2009, 23(4), 791-815, vii.
[ ] [PMID: 19909885]
Mylonakis, E.; Ryan, E.T.; Calderwood, S.B. Clostridium difficile--Associated diarrhea: A review. Arch. Intern. Med., 2001, 161(4), 525-533.
[] [PMID: 11252111]
Denève, C.; Deloménie, C.; Barc, M.C.; Collignon, A.; Janoir, C. Antibiotics involved in Clostridium difficile-associated disease increase colonization factor gene expression. J. Med. Microbiol., 2008, 57(Pt 6), 732-738.
[] [PMID: 18480330]
Siberry, G.K.; Tekle, T.; Carroll, K.; Dick, J. Failure of clindamycin treatment of methicillin-resistant Staphylococcus aureus expressing inducible clindamycin resistance in vitro. Clin. Infect. Dis., 2003, 37(9), 1257-1260.
[] [PMID: 14557972]
McClure, J.A.; Conly, J.M.; Lau, V.; Elsayed, S.; Louie, T.; Hutchins, W.; Zhang, K. Novel multiplex PCR assay for detection of the staphylococcal virulence marker Panton-Valentine leukocidin genes and simultaneous discrimination of methicillin-susceptible from -resistant staphylococci. J. Clin. Microbiol., 2006, 44(3), 1141-1144.
[] [PMID: 16517915]
Wayne, P.A. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard, CLSI document M7-A7, 7th; Clinical and Laboratory Standards Institute, 2006.
Clinical and laboratory standards institute. Performance standards for antimicrobial susceptibility testing. Seventeenth informational supplement Clinical Laboratory Standards Institute, 2007.
Tsuji, M.; Takema, M.; Miwa, H.; Shimada, J.; Kuwahara, S. In vivo antibacterial activity of S-3578, a new broad-spectrum cephalosporin: methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa experimental infection models. Antimicrob. Agents Chemother., 2003, 47(8), 2507-2512.
[] [PMID: 12878512]
O’Reilly, T.; Kunz, S.; Sande, E.; Zak, O.; Sande, M.A.; Täuber, M.G. Relationship between antibiotic concentration in bone and efficacy of treatment of staphylococcal osteomyelitis in rats: azithromycin compared with clindamycin and rifampin. Antimicrob. Agents Chemother., 1992, 36(12), 2693-2697.
[] [PMID: 1336342]
Kasai, T.; Tanaka, T.; Kiriyama, S.; Sonoyama, K. Facile preparation of rat intestinal mucosa for assay of mucosal enzyme activity. J. Nutr. Sci. Vitaminol. (Tokyo), 1993, 39(4), 399-403.
[] [PMID: 8283318]
Ki, V.; Rotstein, C. Bacterial skin and soft tissue infections in adults: A review of their epidemiology, pathogenesis, diagnosis, treatment and site of care. Can. J. Infect. Dis. Med. Microbiol., 2008, 19(2), 173-184.
[] [PMID: 19352449]
Eckmann, C.; Dryden, M. Treatment of complicated skin and soft-tissue infections caused by resistant bacteria: value of linezolid, tigecycline, daptomycin and vancomycin. Eur. J. Med. Res., 2010, 15(12), 554-563.
[] [PMID: 21163730]
Vivekanandan, L.; Sheik, H.; Singaravel, S.; Thangavel, S. Ameliorative effect of silymarin against linezolid-induced hepatotoxicity in methicillin-resistant Staphylococcus aureus (MRSA) infected Wistar rats. Biomed. Pharmacother., 2018, 108, 1303-1312.
[] [PMID: 30372832]
Adhikari, R.P.; Shrestha, S.; Barakoti, A.; Amatya, R. Inducible clindamycin and methicillin resistant Staphylococcus aureus in a tertiary care hospital, Kathmandu, Nepal. BMC Infect. Dis., 2017, 17(1), 483.
[] [PMID: 28693489]
Daum, R.S.; Miller, L.G.; Immergluck, L.; Fritz, S.; Creech, C.B.; Young, D.; Kumar, N.; Downing, M.; Pettibone, S.; Hoagland, R.; Eells, S.J.; Boyle, M.G.; Parker, T.C.; Chambers, H.F. DMID 07-0051 Team. A placebo –controlled trial of antibiotics for smaller skin abscess. N. Engl. J. Med., 2017, 376(26), 2545-2555.
[] [PMID: 28657870]
Hodille, E.; Badiou, C.; Bouveyron, C.; Bes, M.; Tristan, A.; Vandenesch, F.; Lina, G.; Dumitrescu, O. Clindamycin suppresses virulence expression in inducible clindamycin-resistant Staphylococcus aureus strains. Ann. Clin. Microbiol. Antimicrob., 2018, 17(1), 38.
[] [PMID: 30342546]
Morales, M.P.; Carvallo, A.P.T.; Espinosa, K.A.B.; Murillo, E.E.M. A young man with myelosuppression caused by clindamycin: a case report. J. Med. Case Reports, 2014, 8, 7.
[] [PMID: 24387005]
Gray, J.E.; Weaver, R.N.; Bollert, J.A.; Feenstra, E.S. The oral toxicity of clindamycin in laboratory animals. Toxicol. Appl. Pharmacol., 1972, 21(4), 516-531.
[] [PMID: 5047049]
Van Dongen, J.M.; Kooyman, J.; Visser, W.J.; Holt, S.J.; Galjaard, H. The effect of increased crypt cell proliferation on the activity and subcellular localization of esterases and alkaline phosphatase in the rat small intestine. Histochem. J., 1977, 9(1), 61-75.
[] [PMID: 830626]
Bates, J.M.; Mittge, E.; Kuhlman, J.; Baden, K.N.; Cheesman, S.E.; Guillemin, K. Distinct signals from the microbiota promote different aspects of zebrafish gut differentiation. Dev. Biol., 2006, 297(2), 374-386.
[] [PMID: 16781702]
Lallès, J.P. Intestinal alkaline phosphatase: novel functions and protective effects. Nutr. Rev., 2014, 72(2), 82-94.
[] [PMID: 24506153]
Fawley, J.; Gourlay, D.M. Intestinal alkaline phosphatase: a summary of its role in clinical disease. J. Surg. Res., 2016, 202(1), 225-234.
[] [PMID: 27083970]
Endt, K.; Stecher, B.; Chaffron, S.; Slack, E.; Tchitchek, N.; Benecke, A.; Van Maele, L.; Sirard, J.C.; Mueller, A.J.; Heikenwalder, M.; Macpherson, A.J.; Strugnell, R.; von Mering, C.; Hardt, W.D. The microbiota mediates pathogen clearance from the gut lumen after non-typhoidal Salmonella diarrhea. PLoS Pathog., 2010, 6(9)e1001097
[] [PMID: 20844578]
Donskey, C.J.; Hanrahan, J.A.; Hutton, R.A.; Rice, L.B. Effect of parenteral antibiotic administration on the establishment of colonization with vancomycin-resistant Enterococcus faecium in the mouse gastrointestinal tract. J. Infect. Dis., 2000, 181(5), 1830-1833.
[] [PMID: 10823795]
Ubeda, C.; Taur, Y.; Jenq, R.R.; Equinda, M.J.; Son, T.; Samstein, M.; Viale, A.; Socci, N.D.; van den Brink, M.R.; Kamboj, M.; Pamer, E.G. Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans. J. Clin. Invest., 2010, 120(12), 4332-4341.
[] [PMID: 21099116]
Vollaard, E.J.; Clasener, H.A. Colonization resistance. Antimicrob. Agents Chemother., 1994, 38(3), 409-414.
[] [PMID: 8203832]
Sullivan, A.; Edlund, C.; Nord, C.E. Effect of antimicrobial agents on the ecological balance of human microflora. Lancet Infect. Dis., 2001, 1(2), 101-114.
[] [PMID: 11871461]
Farooq, P.D.; Urrunaga, N.H.; Tang, D.M.; von Rosenvinge, E.C. Pseudomembranous colitis. Dis. Mon., 2015, 61(5), 181-206.
[] [PMID: 25769243]
Johnson, J.T.; Wagner, R.L.; Schuller, D.E.; Gluckman, J.; Suen, J.Y.; Snyderman, N.L. Prophylactic antibiotics for head and neck surgery with flap reconstruction. Arch. Otolaryngol. Head Neck Surg., 1992, 118(5), 488-490.
[] [PMID: 1571118]

© 2022 Bentham Science Publishers | Privacy Policy