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Current Diabetes Reviews

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ISSN (Print): 1573-3998
ISSN (Online): 1875-6417

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Review Article

Treatment Strategies Against Diabetic Foot Ulcer: Success so Far and the Road Ahead

Author(s): Ankit Awasthi, Sachin Kumar Singh*, Bimlesh Kumar, Monica Gulati, Rajesh Kumar, Sheetu Wadhwa, Rubiya Khursheed, Leander Corrie, Arya KR, Rajan Kumar, Pooja Patni, Jaskiran Kaur, Sukriti Vishwas and Ankit Yadav

Volume 17, Issue 4, 2021

Published on: 02 November, 2020

Page: [421 - 436] Pages: 16

DOI: 10.2174/1573399816999201102125537

Price: $65

Abstract

Background: Diabetic foot ulcer (DFU) is one of the leading complications of type-2 diabetes mellitus. It is associated with neuropathy and peripheral arterial disease of the lower limb in patients with diabetes. There are four stages of wound healing, namely hemostasis phase, inflammatory phase, proliferative phase and maturation phase. In the case of DFU, all these stages are disturbed which lead to delay in healing and consequently to lower limb amputation. Conventional dosage forms like tablets, creams, ointments, gels and capsules have been used for the treatment of diabetic foot ulcer for many years.

Introduction: In this review, the global prevalence as well as etiopathogenesis related to diabetic foot ulcer have been discussed. The potential role of various synthetic and herbal drugs, as well as their conventional dosage forms in the effective management of DFU have been discussed in detail.

Methods: Structured search of bibliographic databases from previously published peer-reviewed research papers was explored and data has been represented in terms of various approaches that are used for the treatment of DFU.

Results: About 148 papers, including both research and review articles, were included in this review to produce a comprehensive as well as a readily understandable article. A series of herbal and synthetic drugs have been discussed along with their current status of treatment in terms of dose and mechanism of action.

Conclusion: DFU has become one of the most common complications in patients having diabetes for more than ten years. Hence, understanding the root cause and its successful treatment is a big challenge because it depends upon multiple factors such as the judicious selection of drugs as well as proper control of blood sugar level. Most of the drugs that have been used so far either belong to the category of antibiotics, antihyperglycaemic or they have been repositioned. In clinical practice, much focus has been given to dressings that have been used to cover the ulcer. The complete treatment of DFU is still a farfetched dream to be achieved and it is expected that combination therapy of herbal and synthetic drugs with multiple treatment pathways could be able to offer better management of DFU.

Keywords: Diabetic foot ulcer, type 2 diabetes mellitus, synthetic drugs, herbal drugs, etiopathogenesis, blood sugar level.

[1]
Radhakrishna K. VVS NRK BM, Kuppusamy G. Potential use of herbal medicines in the treatment of diabetic foot ulcers. History (Lond) 2014; 14(56): 34-42.
[2]
Kaur N, Fernandez R, Sim J. Effect of Aloe vera on glycemic outcomes in patients with diabetes mellitus: a systematic review protocol. JBI Database Syst Rev Implement Reports 2017; 15(9): 2300-6.
[http://dx.doi.org/10.11124/JBISRIR-2016-002958] [PMID: 28902697]
[3]
Ramachandran A. Know the signs and symptoms of diabetes. Indian J Med Res 2014; 140(5): 579-81.
[PMID: 25579136]
[4]
Kitabchi AE, Umpierrez GE, Miles JM, Fisher JN. Hyperglycemic crises in adult patients with diabetes. Diabetes Care 2009; 32(7): 1335-43.
[http://dx.doi.org/10.2337/dc09-9032] [PMID: 19564476]
[5]
Alexiadou K, Doupis J. Management of diabetic foot ulcers. Diabetes Ther 2012; 3(1): 4.
[http://dx.doi.org/10.1007/s13300-012-0004-9] [PMID: 22529027]
[6]
Natarajan J, Sanapalli BKR, Bano M, Singh SK, Gulati M, Karri VVSR. Nanostructured Lipid Carriers of Pioglitazone Loaded Collagen/Chitosan Composite Scaffold for Diabetic Wound Healing. Adv Wound Care (New Rochelle) 2019; 8(10): 499-513.
[http://dx.doi.org/10.1089/wound.2018.0831] [PMID: 31737408]
[7]
Aumiller WD, Dollahite HA. Pathogenesis and management of diabetic foot ulcers. JAAPA 2015; 28(5): 28-34.
[http://dx.doi.org/10.1097/01.JAA.0000464276.44117.b1] [PMID: 25853673]
[8]
Ogurtsova K, da Rocha Fernandes JD, Huang Y, et al. IDF Diabetes Atlas: Global estimates for the prevalence of diabetes for 2015 and 2040. Diabetes Res Clin Pract 2017; 128: 40-50.
[http://dx.doi.org/10.1016/j.diabres.2017.03.024] [PMID: 28437734]
[9]
Ibrahim AM. Diabetic Foot Ulcer: Synopsis of the Epidemiology and Pathophysiology. Int J Diabetes Endocrin 2018; 3(2): 23.
[http://dx.doi.org/10.11648/j.ijde.20180302.11]
[10]
Bus SA, Lavery L, Monteiro-Soares M, Rasmussen A, Raspovic A, Sacco I. IWGDF Guideline on the prevention of foot ulcers in persons with diabetes. Diabetes Metab Res Rev 2019; 5-67.
[11]
Ibrahim A. IDF clinical practice recommendation on the diabetic foot: a guide for healthcare professionals. diabetes research and clinical practice 2017; 127: 285-7.
[12]
Murphy-Lavoie HM, Bhimji SS. Diabetic, Foot Infections. StatPearls [Internet]: StatPearls Publishing 2017.
[13]
Ghosh P, Valia R. Burden of Diabetic Foot Ulcers in India: Evidence Landscape from Published Literature. Value Health 2017; 20(9): A485.
[http://dx.doi.org/10.1016/j.jval.2017.08.489]
[14]
Vibha SP, Kulkarni MM, Kirthinath Ballala AB, Kamath A, Maiya GA. Community based study to assess the prevalence of diabetic foot syndrome and associated risk factors among people with diabetes mellitus. BMC Endocr Disord 2018; 18(1): 43.
[http://dx.doi.org/10.1186/s12902-018-0270-2] [PMID: 29940924]
[15]
Paisey RB, Abbott A, Levenson R, et al. South-West Cardiovascular Strategic Clinical Network peer diabetic foot service review team. Diabetes-related major lower limb amputation incidence is strongly related to diabetic foot service provision and improves with enhancement of services: peer review of the South-West of England. Diabet Med 2018; 35(1): 53-62.
[http://dx.doi.org/10.1111/dme.13512] [PMID: 29023974]
[16]
Boyko EJ, Monteiro-Soares M. Epidemiology and Economic Impact of Foot Ulcers. The Foot in Diabet 2020; 1-15.
[http://dx.doi.org/10.1002/9781119445821.ch1]
[17]
Zhang P, Lu J, Jing Y, Tang S, Zhu D, Bi Y. Global epidemiology of diabetic foot ulceration: a systematic review and meta-analysis †. Ann Med 2017; 49(2): 106-16.
[http://dx.doi.org/10.1080/07853890.2016.1231932] [PMID: 27585063]
[18]
Orsted H, Keast D, Forest-Laland L, Kuhnke J, O’Sullivan-Drombolis D, Jin S. Foundations of best practice for skin and wound management. Chapter 2 Best practice recommendations for the prevention and management of wounds 2018.
[19]
Ahmed AA, Algamdi SA, Algurashi A, Alzhrani AM, Khalid KA. Risk factors for diabetic foot ulceration among patients attending primary health care services. J Diabet Foot Complications 2014; 6: 40-7.
[20]
G SB, Choi S, Krishnan J, K R. Cigarette smoke and related risk factors in neurological disorders: An update. Biomed Pharmacother 2017; 85: 79-86.
[http://dx.doi.org/10.1016/j.biopha.2016.11.118] [PMID: 27930990]
[21]
Knight-Lozano CA, Young CG, Burow DL, et al. Cigarette smoke exposure and hypercholesterolemia increase mitochondrial damage in cardiovascular tissues. Circulation 2002; 105(7): 849-54.
[http://dx.doi.org/10.1161/hc0702.103977] [PMID: 11854126]
[22]
Masayesva BG, Mambo E, Taylor RJ, et al. Mitochondrial DNA content increase in response to cigarette smoking. Cancer Epidemiol Biomarkers Prev 2006; 15(1): 19-24.
[http://dx.doi.org/10.1158/1055-9965.EPI-05-0210] [PMID: 16434581]
[23]
Lee J-M, Li J, Johnson DA, et al. Nrf2, a multi-organ protector? FASEB J 2005; 19(9): 1061-6.
[http://dx.doi.org/10.1096/fj.04-2591hyp] [PMID: 15985529]
[24]
Silverstein P. Smoking and wound healing. Am J Med 1992; 93(1A): 22S-4S.
[http://dx.doi.org/10.1016/0002-9343(92)90623-J] [PMID: 1323208]
[25]
Cervantes-García E, Salazar-Schettino PM. Clinical and surgical characteristics of infected diabetic foot ulcers in a tertiary hospital of Mexico. Diabet Foot Ankle 2017; 8(1): 1367210.
[http://dx.doi.org/10.1080/2000625X.2017.1367210] [PMID: 28904744]
[26]
Mooradian AD. Dyslipidemia in type 2 diabetes mellitus. Nat Clin Pract Endocrinol Metab 2009; 5(3): 150-9.
[PMID: 19229235]
[27]
Briaud I, Harmon JS, Kelpe CL, Segu VBG, Poitout V. Lipotoxicity of the pancreatic β-cell is associated with glucose-dependent esterification of fatty acids into neutral lipids. Diabetes 2001; 50(2): 315-21.
[http://dx.doi.org/10.2337/diabetes.50.2.315] [PMID: 11272142]
[28]
Lee Y, Hirose H, Ohneda M, Johnson JH, McGarry JD, Unger RH. Beta-cell lipotoxicity in the pathogenesis of non-insulin-dependent diabetes mellitus of obese rats: impairment in adipocyte- beta-cell relationships. Proc Natl Acad Sci USA 1994; 91(23): 10878-82.
[http://dx.doi.org/10.1073/pnas.91.23.10878] [PMID: 7971976]
[29]
Zheng S, Xu H, Zhou H, et al. Associations of lipid profiles with insulin resistance and β cell function in adults with normal glucose tolerance and different categories of impaired glucose regulation. PLoS One 2017; 12(2): e0172221.
[http://dx.doi.org/10.1371/journal.pone.0172221] [PMID: 28199386]
[30]
Rachek LI. Free fatty acids and skeletal muscle insulin resistance. Progress in molecular biology and translational science. Elsevier 2014; pp. 267-92.
[31]
Goldberg IJ. Clinical review 124: Diabetic dyslipidemia: causes and consequences. J Clin Endocrinol Metab 2001; 86(3): 965-71.
[http://dx.doi.org/10.1210/jcem.86.3.7304] [PMID: 11238470]
[32]
Krauss RM. Lipids and lipoproteins in patients with type 2 diabetes. Diabetes Care 2004; 27(6): 1496-504.
[http://dx.doi.org/10.2337/diacare.27.6.1496] [PMID: 15161808]
[33]
Vergès B, Duvillard L, Lagrost L, et al. Changes in lipoprotein kinetics associated with type 2 diabetes affect the distribution of lipopolysaccharides among lipoproteins. J Clin Endocrinol Metab 2014; 99(7): E1245-53.
[http://dx.doi.org/10.1210/jc.2013-3463] [PMID: 24694333]
[34]
Lee JS, Chang P-Y, Zhang Y, Kizer JR, Best LG, Howard BV. Triglyceride and HDL-C dyslipidemia and risks of coronary heart disease and ischemic stroke by glycemic dysregulation status: the strong heart study. Diabetes Care 2017; 40(4): 529-37.
[http://dx.doi.org/10.2337/dc16-1958] [PMID: 28122840]
[35]
Giles TD, Materson BJ, Cohn JN, Kostis JB. Definition and classification of hypertension: an update. J Clin Hypertens (Greenwich) 2009; 11(11): 611-4.
[http://dx.doi.org/10.1111/j.1751-7176.2009.00179.x] [PMID: 19878368]
[36]
Head GA, Mihailidou AS, Duggan KA, et al. Ambulatory blood pressure working group of the high blood pressure research council of australia. Definition of ambulatory blood pressure targets for diagnosis and treatment of hypertension in relation to clinic blood pressure: prospective cohort study. BMJ 2010; 340: c1104.
[http://dx.doi.org/10.1136/bmj.c1104] [PMID: 20392760]
[37]
Greco D, Sinagra D. Hyperinsulinism/insulin resistance: cause, effect or marker of essential arterial hypertension? G Ital Cardiol 1995; 25(2): 207-16.
[PMID: 7642026]
[38]
Sowers JR. Insulin resistance and hypertension. American Physiological Society 2004.
[http://dx.doi.org/10.1152/ajpheart.00026.2004]
[39]
Zhou M-S, Wang A, Yu H. Link between insulin resistance and hypertension: What is the evidence from evolutionary biology? Diabetol Metab Syndr 2014; 6(1): 12.
[http://dx.doi.org/10.1186/1758-5996-6-12] [PMID: 24485020]
[40]
Salvetti A, Brogi G, Di Legge V, Bernini GP. The inter-relationship between insulin resistance and hypertension. Drugs 1993; 46(2)(Suppl. 2): 149-59.
[http://dx.doi.org/10.2165/00003495-199300462-00024] [PMID: 7512468]
[41]
Ahmed AA, Mooar PA, Kleiner M, Torg JS, Miyamoto CT. Hypertensive patients show delayed wound healing following total hip arthroplasty. PLoS One 2011; 6(8): e23224.
[http://dx.doi.org/10.1371/journal.pone.0023224] [PMID: 21853091]
[42]
Papatheodorou K, Banach M, Bekiari E, Rizzo M, Edmonds M. Complications of diabetes 2017. J Diabet Res 2018; 2018: 3086167.
[43]
Papatheodorou K, Papanas N, Banach M, Papazoglou D, Edmonds M. Complications of diabetes 2016. J Diabet Res 2016; 2016: 6989453.
[44]
Yagihashi S, Mizukami H, Sugimoto K. Mechanism of diabetic neuropathy: Where are we now and where to go? J Diabetes Investig 2011; 2(1): 18-32.
[http://dx.doi.org/10.1111/j.2040-1124.2010.00070.x] [PMID: 24843457]
[45]
Hwang DJ, Lee KM, Park MS, et al. Association between diabetic foot ulcer and diabetic retinopathy. PLoS One 2017; 12(4): e0175270.
[http://dx.doi.org/10.1371/journal.pone.0175270] [PMID: 28388680]
[46]
Bakker K, Abbas Z, Pendsey S. Step by step, improving diabetic foot care in the developing world. Pract Diabetes Int 2006; 23(8): 365-9.
[http://dx.doi.org/10.1002/pdi.1012]
[47]
Tulley S, Foster A, van Putten M, Urbancic-Rovan V, Bakker K. Diabetic foot care training in developing countries: Addressing the skills shortage. The Diabet Foot J 2009; 12(1)
[48]
Van Netten JJ, Apelqvist J, Bus SA, Hinchliffe RJ, Lipsky BA, Schaper NC. New IWGDF Guidelines on Prevention and Management of Diabetic Foot Disease released.. 2020;23(1). Diabetic Foot Journal 2020; 23(1)
[49]
Kumar M, Jaiswal S, Sodhi KK, et al. Antibiotics bioremediation: Perspectives on its ecotoxicity and resistance. Environ Int 2019; 124: 448-61.
[http://dx.doi.org/10.1016/j.envint.2018.12.065] [PMID: 30684803]
[50]
Peter Blume D. FACFAS, Brittany Ciaramello, DPM, Michelle Kaufman, DPM, and Shane Reynolds, DPM. Top 10 Antibiotics For Managing Diabetic Foot Infections. Podiatry Today 2017; 30(8): 36-41.
[51]
Patel S, Bernice F. StatPearls [Internet]: StatPearls Publishing 2018.
[52]
Lee T, Pang S, Abraham S, Coombs GW. Antimicrobial-resistant CC17 Enterococcus faecium: The past, the present and the future. J Glob Antimicrob Resist 2019; 16: 36-47.
[http://dx.doi.org/10.1016/j.jgar.2018.08.016] [PMID: 30149193]
[53]
Bartoletti M, Giannella M, Tedeschi S, Viale P. Multidrug-Resistant Bacterial Infections in Solid Organ Transplant Candidates and Recipients. Infect Dis Clin North Am 2018; 32(3): 551-80.
[http://dx.doi.org/10.1016/j.idc.2018.04.004] [PMID: 30146023]
[54]
Niu S-C, Deng S-T, Lee M-H, Ho C, Chang H-Y, Liu F-H. Modified vancomycin dosing protocol for treatment of diabetic foot infections. Am J Health Syst Pharm 2008; 65(18): 1740-3.
[http://dx.doi.org/10.2146/ajhp080004] [PMID: 18769001]
[55]
Richards DM, Brogden RN. Ceftazidime. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs 1985; 29(2): 105-61.
[http://dx.doi.org/10.2165/00003495-198529020-00002] [PMID: 3884319]
[56]
Hayes MV, Orr DC. Mode of action of ceftazidime: affinity for the penicillin-binding proteins of Escherichia coli K12, Pseudomonas aeruginosa and Staphylococcus aureus. J Antimicrob Chemother 1983; 12(2): 119-26.
[http://dx.doi.org/10.1093/jac/12.2.119] [PMID: 6413485]
[57]
Lipsky BA, Berendt AR, Deery HG, et al. Infectious Diseases Society of America. Diagnosis and treatment of diabetic foot infections. Clin Infect Dis 2004; 39(7): 885-910.
[http://dx.doi.org/10.1086/424846] [PMID: 15472838]
[58]
Freeman CD, Klutman NE, Lamp KC. Metronidazole. A therapeutic review and update. Drugs 1997; 54(5): 679-708.
[http://dx.doi.org/10.2165/00003495-199754050-00003] [PMID: 9360057]
[59]
Edwards DI. Nitroimidazole drugs-action and resistance mechanisms. I. Mechanisms of action. J Antimicrob Chemother 1993; 31(1): 9-20.
[http://dx.doi.org/10.1093/jac/31.1.9] [PMID: 8444678]
[60]
Edwards DI, Ed. Reduction of nitroimidazoles in vitro and DNA damage. Bioreduction in the Activation of Drugs Proceedings of the Second Biochemical Pharmacology Symposium. Oxford, UK. Elsevier. 2013.25-26 July 1985;
[61]
Muller M, Ed. Reductive activation of nitroimidazoles in anaerobic microorganisms. Bioreduction in the Activation of Drugs Proceedings of the Second Biochemical Pharmacology Symposium. Oxford, UK. Elsevier. 2013.25-26 July 1985;
[62]
Barwell ND, Devers MC, Kennon B, et al. Diabetic foot infection: Antibiotic therapy and good practice recommendations. Int J Clin Pract 2017; 71(10): e13006.
[http://dx.doi.org/10.1111/ijcp.13006] [PMID: 28892282]
[63]
Agwuh K, Hosker-Diabetologist J. Skin and Soft Tissue Infection Guideline, including Diabetic Foot Ulcer Infection 2012.
[64]
Tan JS, File TM Jr. Antipseudomonal penicillins. Med Clin North Am 1995; 79(4): 679-93.
[http://dx.doi.org/10.1016/S0025-7125(16)30032-3] [PMID: 7791416]
[65]
Tong MKH, Siu Y-P, Yung C-Y, Kwan T-H. Piperacillin/tazobactam-induced acute delirium in a peritoneal dialysis patient. Nephrol Dial Transplant 2004; 19(5): 1341.
[http://dx.doi.org/10.1093/ndt/gfh048] [PMID: 15102992]
[66]
Placzek M, Whitelaw A, Want S, Sahathevan M, Darrell J. Piperacillin in early neonatal infection. Arch Dis Child 1983; 58(12): 1006-9.
[http://dx.doi.org/10.1136/adc.58.12.1006] [PMID: 6559060]
[67]
Sarkar P, Yarlagadda V, Ghosh C, Haldar J. A review on cell wall synthesis inhibitors with an emphasis on glycopeptide antibiotics. MedChemComm 2017; 8(3): 516-33.
[http://dx.doi.org/10.1039/C6MD00585C] [PMID: 30108769]
[68]
Collins LA, Wennersten CB, Ferraro MJ, Moellering RC Jr, Eliopoulos GM. Comparative activities of piperacillin and tazobactam against clinical isolates of Legionella spp. Antimicrob Agents Chemother 1994; 38(1): 144-6.
[http://dx.doi.org/10.1128/AAC.38.1.144] [PMID: 8141570]
[69]
Bryson HM, Brogden RN. Piperacillin/tazobactam. A review of its antibacterial activity, pharmacokinetic properties and therapeutic potential. Drugs 1994; 47(3): 506-35.
[http://dx.doi.org/10.2165/00003495-199447030-00008] [PMID: 7514977]
[70]
Bonomo RA, Rudin SA, Shlaes DM. Tazobactam is a potent inactivator of selected inhibitor-resistant class A β-lactamases. FEMS Microbiol Lett 1997; 148(1): 59-62.
[http://dx.doi.org/10.1016/S0378-1097(97)00013-X] [PMID: 9066111]
[71]
Schechter LM, Creely DP, Garner CD, et al. Extensive gene amplification as a mechanism for piperacillin-tazobactam resistance in Escherichia coli. MBio 2018; 9(2): e00583-18.
[http://dx.doi.org/10.1128/mBio.00583-18] [PMID: 29691340]
[72]
Pagan-Rodriguez D, Zhou X, Simmons R, et al. Tazobactam inactivation of SHV-1 and the inhibitor-resistant Ser130 ->Gly SHV-1 β-lactamase: insights into the mechanism of inhibition. J Biol Chem 2004; 279(19): 19494-501.
[http://dx.doi.org/10.1074/jbc.M311669200] [PMID: 14757767]
[73]
Legat FJ, Krause R, Zenahlik P, et al. Penetration of piperacillin and tazobactam into inflamed soft tissue of patients with diabetic foot infection. Antimicrob Agents Chemother 2005; 49(10): 4368-71.
[http://dx.doi.org/10.1128/AAC.49.10.4368-4371.2005] [PMID: 16189124]
[74]
Reddy KR, Brillant P, Schiff ER. Amoxicillin-clavulanate potassium-associated cholestasis. Gastroenterology 1989; 96(4): 1135-41.
[http://dx.doi.org/10.1016/0016-5085(89)91633-8] [PMID: 2925057]
[75]
Evans J, Wittler M. StatPearls [Internet]: StatPearls Publishing 2019.
[76]
Brogden RN, Carmine A, Heel RC, Morley PA, Speight TM, Avery GS. Amoxycillin/clavulanic acid: a review of its antibacterial activity, pharmacokinetics and therapeutic use. Drugs 1981; 22(5): 337-62.
[http://dx.doi.org/10.2165/00003495-198122050-00001] [PMID: 7037354]
[77]
Stein GE, Gurwith MJ. Amoxicillin-potassium clavulanate, a beta-lactamase-resistant antibiotic combination. Clin Pharm 1984; 3(6): 591-9.
[PMID: 6391783]
[78]
Wise R, Andrews JM, Bedford KA. in vitro study of clavulanic acid in combination with penicillin, amoxycillin, and carbenicillin. Antimicrob Agents Chemother 1978; 13(3): 389-93.
[http://dx.doi.org/10.1128/AAC.13.3.389] [PMID: 122520]
[79]
White AR, Kaye C, Poupard J, Pypstra R, Woodnutt G, Wynne B. Augmentin®(amoxicillin/clavulanate) in the treatment of community-acquired respiratory tract infection: a review of the continuing development of an innovative antimicrobial agent. J Antimicrob Chemother 2004; 53 (suppl_1 ): 13 -120 .
[80]
Lipsky BA, Itani K, Norden C, Group LDFIS. Linezolid Diabetic Foot Infections Study Group. Treating foot infections in diabetic patients: a randomized, multicenter, open-label trial of linezolid versus ampicillin-sulbactam/amoxicillin-clavulanate. Clin Infect Dis 2004; 38(1): 17-24.
[http://dx.doi.org/10.1086/380449] [PMID: 14679443]
[81]
Smieja M. Current indications for the use of clindamycin: A critical review. Can J Infect Dis 1998; 9(1): 22-8.
[http://dx.doi.org/10.1155/1998/538090] [PMID: 22346533]
[82]
Murphy PB, Le JK. StatPearls [Internet]: StatPearls Publishing 2019.
[83]
Liu C, Bayer A, Cosgrove SE, et al. Infectious Diseases Society of America. Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children. Clin Infect Dis 2011; 52(3): e18-55.
[http://dx.doi.org/10.1093/cid/ciq146] [PMID: 21208910]
[84]
Peechakara BV, Gupta M. StatPearls [Internet]: StatPearls Publishing 2018.
[85]
Kanra G. Experience with ampicillin/sulbactam in severe infections. J Internation Med Res 2002; 30 (1_suppl ): 20 -30 .
[86]
Rafailidis PI, Ioannidou EN, Falagas ME. Ampicillin/sulbactam: current status in severe bacterial infections. Drugs 2007; 67(13): 1829-49.
[http://dx.doi.org/10.2165/00003495-200767130-00003] [PMID: 17722953]
[87]
Munshi MN, Lipsitz LA. Geriatric diabetes: CRC Press 2007.
[http://dx.doi.org/10.3109/9781420019810]
[88]
Hooper DC, Wolfson JS. Fluoroquinolone antimicrobial agents. N Engl J Med 1991; 324(6): 384-94.
[http://dx.doi.org/10.1056/NEJM199102073240606] [PMID: 1987461]
[89]
Thai T, Zito PM. StatPearls [Internet]: StatPearls Publishing 2018.
[90]
Peyriere H, Makinson A, Marchandin H, Reynes J. Doxycycline in the management of sexually transmitted infections. J Antimicrob Chemother 2018; 73(3): 553-63.
[PMID: 29182717]
[91]
Schnappinger D, Hillen W. Tetracyclines: antibiotic action, uptake, and resistance mechanisms. Arch Microbiol 1996; 165(6): 359-69.
[http://dx.doi.org/10.1007/s002030050339] [PMID: 8661929]
[92]
Pham P. Ertapenem (INVANZ): A New Once a Day Carbapenem. Infect Dis Clin Pract 2002; 11(1): 30-1.
[http://dx.doi.org/10.1097/00019048-200201000-00008]
[93]
Keating GM, Perry CM. Ertapenem: a review of its use in the treatment of bacterial infections. Drugs 2005; 65(15): 2151-78.
[http://dx.doi.org/10.2165/00003495-200565150-00013] [PMID: 16225376]
[94]
Mouton JW, Touzw DJ, Horrevorts AM, Vinks AA. Comparative pharmacokinetics of the carbapenems: clinical implications. Clin Pharmacokinet 2000; 39(3): 185-201.
[http://dx.doi.org/10.2165/00003088-200039030-00002] [PMID: 11020134]
[95]
Zhanel GG, Wiebe R, Dilay L, et al. Comparative review of the carbapenems. Drugs 2007; 67(7): 1027-52.
[http://dx.doi.org/10.2165/00003495-200767070-00006] [PMID: 17488146]
[96]
Sumita Y, Fukasawa M. Potent activity of meropenem against Escherichia coli arising from its simultaneous binding to penicillin-binding proteins 2 and 3. J Antimicrob Chemother 1995; 36(1): 53-64.
[http://dx.doi.org/10.1093/jac/36.1.53] [PMID: 8537284]
[97]
Codjoe FS, Donkor ES. Carbapenem resistance: a review. Med Sci (Basel) 2017; 6(1): 1.
[http://dx.doi.org/10.3390/medsci6010001] [PMID: 29267233]
[98]
Edmonds M. The treatment of diabetic foot infections: focus on ertapenem. Vasc Health Risk Manag 2009; 5: 949-63.
[http://dx.doi.org/10.2147/VHRM.S3162] [PMID: 19997576]
[99]
Masadeh M, Mhaidat N, Alzoubi K, Al-Azzam S, Alnasser Z. Antibacterial activity of statins: a comparative study of atorvastatin, simvastatin, and rosuvastatin. Ann Clin Microbiol Antimicrob 2012; 11(1): 13.
[http://dx.doi.org/10.1186/1476-0711-11-13] [PMID: 22564676]
[100]
McIver LA, Siddique MS. StatPearls [Internet]: StatPearls Publishing 2019.
[101]
Gulcan E, Gulcan A, Erbilen E, Toker S. Statins may be useful in diabetic foot ulceration treatment and prevention. Med Hypotheses 2007; 69(6): 1313-5.
[PMID: 17499447]
[102]
Vasa M, Fichtlscherer S, Adler K, et al. Increase in circulating endothelial progenitor cells by statin therapy in patients with stable coronary artery disease. Circulation 2001; 103(24): 2885-90.
[PMID: 11413075]
[103]
Johansen OE, Birkeland KI, Jørgensen AP, et al. Diabetic foot ulcer burden may be modified by high-dose atorvastatin: A 6-month randomized controlled pilot trial. J Diabetes 2009; 1(3): 182-7.
[http://dx.doi.org/10.1111/j.1753-0407.2009.00031.x] [PMID: 20923537]
[104]
Sawaya AP, Pastar I, Stojadinovic O, et al. Topical mevastatin promotes wound healing by inhibiting the transcription factor c-Myc via the glucocorticoid receptor and the long non-coding RNA Gas5. J Biol Chem 2018; 293(4): 1439-49.
[http://dx.doi.org/10.1074/jbc.M117.811240] [PMID: 29158265]
[105]
Farmer AR, Murray CK, Mende K, et al. Effect of HMG-CoA reductase inhibitors on antimicrobial susceptibilities for gram-negative rods. J Basic Microbiol 2013; 53(4): 336-9.
[http://dx.doi.org/10.1002/jobm.201100614] [PMID: 22736455]
[106]
Vukelic S, Stojadinovic O, Pastar I, et al. Cortisol synthesis in epidermis is induced by IL-1 and tissue injury. J Biol Chem 2011; 286(12): 10265-75.
[http://dx.doi.org/10.1074/jbc.M110.188268] [PMID: 21239489]
[107]
Vukelic S, Stojadinovic O, Pastar I, et al. Farnesyl pyrophosphate inhibits epithelialization and wound healing through the glucocorticoid receptor. J Biol Chem 2010; 285(3): 1980-8.
[http://dx.doi.org/10.1074/jbc.M109.016741] [PMID: 19903814]
[108]
Stojadinovic O, Lebrun E, Pastar I, Kirsner R, Davis SC, Tomic- Canic M. Statins as potential therapeutic agents for healing disorders. Expert Rev Dermatol 2010; 5(6): 689-98.
[http://dx.doi.org/10.1586/edm.10.60]
[109]
Amin-Hanjani S, Stagliano NE, Yamada M, Huang PL, Liao JK, Moskowitz MA. Mevastatin, an HMG-CoA reductase inhibitor, reduces stroke damage and upregulates endothelial nitric oxide synthase in mice. Stroke 2001; 32(4): 980-6.
[http://dx.doi.org/10.1161/01.STR.32.4.980] [PMID: 11283400]
[110]
Asai J, Takenaka H, Hirakawa S, et al. Topical simvastatin accelerates wound healing in diabetes by enhancing angiogenesis and lymphangiogenesis. Am J Pathol 2012; 181(6): 2217-24.
[PMID: 23138019]
[111]
Sameh N, Aly U, Abou-Taleb H, Abdellatif A. Prospective role of simvastatin on wound healing: review of the literature. J Bioequivalence Bioavailab 2018; 10(2): 36-42.
[http://dx.doi.org/10.4172/0975-0851.1000375]
[112]
Khoshneviszadeh M, Ashkani-Esfahani S, Namazi MR, Noorafshan A, Geramizadeh B, Miri R. Topical simvastatin enhances tissue regeneration in full-thickness skin wounds in rat models. Iran J Pharm Res 2014; 13(1): 263-9.
[PMID: 24734079]
[113]
Gismondi RA, Bedirian R, Pozzobon CR, Ladeira MC, Oigman W, Neves MF. Renin-angiotensin system blockade associated with statin improves endothelial function in diabetics. Arq Bras Cardiol 2015; 105(6): 597-605.
[http://dx.doi.org/10.5935/abc.20150123] [PMID: 26465872]
[114]
de Sotomayor MÁ, Pérez-Guerrero C, Herrrera MD, et al. Improvement of age-related endothelial dysfunction by simvastatin: effect on NO and COX pathways. Br J Pharmacol 2005; 146(8): 1130-8.
[http://dx.doi.org/10.1038/sj.bjp.0706420] [PMID: 16231003]
[115]
Nagasarapu M. Simvastatin and its application in wound healing and skin disorders: A review. Pharm Pharmacol Int J 2018; 6(6): 441-7.
[116]
Corcoran C, Jacobs TF. StatPearls [Internet]: StatPearls Publishing 2018.
[117]
Ainuddin JA, Karim N, Zaheer S, Ali SS, Hasan AA. Metformin treatment in type 2 diabetes in pregnancy: an active controlled, parallel-group, randomized, open label study in patients with type 2 diabetes in pregnancy. J Diabet Res 2015.
[http://dx.doi.org/10.1155/2015/325851]
[118]
Malik F, Mehdi SF, Ali H, et al. Is metformin poised for a second career as an antimicrobial? Diabetes Metab Res Rev 2018; 34(4): e2975.
[http://dx.doi.org/10.1002/dmrr.2975] [PMID: 29271563]
[119]
Han X, Tao Y, Deng Y, Yu J, Sun Y, Jiang G. Metformin accelerates wound healing in type 2 diabetic db/db mice. Mol Med Rep 2017; 16(6): 8691-8.
[http://dx.doi.org/10.3892/mmr.2017.7707] [PMID: 28990070]
[120]
Rena G, Hardie DG, Pearson ER. The mechanisms of action of metformin. Diabetologia 2017; 60(9): 1577-85.
[http://dx.doi.org/10.1007/s00125-017-4342-z] [PMID: 28776086]
[121]
Minamii T, Nogami M, Ogawa W. Mechanisms of metformin action: In and out of the gut. J Diabetes Investig 2018; 9(4): 701-3.
[http://dx.doi.org/10.1111/jdi.12864] [PMID: 29777629]
[122]
Prakash A. Managing hyperglycaemia in diabetic foot. JIMSA 2011; 24(4): 213-5.
[123]
Karimi A, Majlesi M, Rafieian-Kopaei M. Herbal versus synthetic drugs; beliefs and facts. J Nephropharmacol 2015; 4(1): 27-30.
[PMID: 28197471]
[124]
Jin S, Zhang M, Gao Y, Zhang X, Cui G, Zhang Y. The efficacy of Jing Wan Hong ointment for nerve injury diabetic foot ulcer and its mechanisms. J Diabetes Res 2014; 2014: 259412.
[http://dx.doi.org/10.1155/2014/259412]
[125]
Lau TW, Chan YW, Lau CP, et al. Radix Astragali and Radix Rehmanniae, the principal components of two antidiabetic foot ulcer herbal formulae, elicit viability-promoting effects on primary fibroblasts cultured from diabetic foot ulcer tissues. Phytother Res 2009; 23(6): 809-15.
[http://dx.doi.org/10.1002/ptr.2649] [PMID: 19148881]
[126]
Li S, Zhao J, Liu J, et al. Prospective randomized controlled study of a Chinese herbal medicine compound Tangzu Yuyang Ointment for chronic diabetic foot ulcers: a preliminary report. J Ethnopharmacol 2011; 133(2): 543-50.
[PMID: 21129474]
[127]
Dogan E, Yanmaz L, Gedikli S, Ersoz U, Okumus Z. The effect of pycnogenol on wound healing in diabetic rats. Ostomy Wound Manage 2017; 63(4): 41-7.
[PMID: 28448268]
[128]
Hotkar MS, Avachat AM, Bhosale SS, Oswal YM. Preliminary investigation of topical nitroglycerin formulations containing natural wound healing agent in diabetes-induced foot ulcer. Int Wound J 2015; 12(2): 210-7.
[PMID: 23731451]
[129]
AlMatar M, Islam MR, Albarri O, Var I, Koksal F. Pomegranate as a possible treatment in reducing risk of developing wound healing, obesity, neurodegenerative disorders, and diabetes mellitus. Mini Rev Med Chem 2018; 18(6): 507-26.
[http://dx.doi.org/10.2174/1389557517666170419114722] [PMID: 28425868]
[130]
Jia H, Yang B, Li Y, et al. Chinese medicine ulcer oil promotes the healing of diabetic foot ulcers. J Int Med Res 2018; 46(7): 2679-86.
[http://dx.doi.org/10.1177/0300060518769529] [PMID: 29916286]
[131]
Mahboubi M, Taghizadeh M, Khamechian T, Tamtaji OR, Mokhtari R, Talaei SA. The Wound Healing Effects of Herbal Cream Containing Oliveria Decumbens and Pelargonium Graveolens Essential Oils in Diabetic Foot Ulcer Model. World J Plast Surg 2018; 7(1): 45-50.
[PMID: 29651391]
[132]
Guo J, Meng Q-H, Yin Q-Y, et al. [Study of effect of tongsaimai tablets on experimental diabetic foot model rats]. Zhongguo Zhongyao Zazhi 2014; 39(11): 2091-6.
[PMID: 25272849]
[133]
Li W, Kandhare AD, Mukherjee AA, Bodhankar SL. Hesperidin, a plant flavonoid accelerated the cutaneous wound healing in streptozotocin-induced diabetic rats: Role of TGF-ß/Smads and Ang-1/Tie-2 signaling pathways. EXCLI J 2018; 17: 399-419.
[PMID: 29805347]
[134]
Tuhin RH, Begum MM, Rahman MS, et al. Wound healing effect of Euphorbia hirta linn. (Euphorbiaceae) in alloxan induced diabetic rats. BMC Complement Altern Med 2017; 17(1): 423.
[http://dx.doi.org/10.1186/s12906-017-1930-x] [PMID: 28836990]
[135]
Zeng Z, Huang WD, Gao Q, et al. Arnebin-1 promotes angiogenesis by inducing eNOS, VEGF and HIF-1α expression through the PI3K-dependent pathway. Int J Mol Med 2015; 36(3): 685-97.
[http://dx.doi.org/10.3892/ijmm.2015.2292] [PMID: 26202335]
[136]
Kittana N, Abu-Rass H, Sabra R, et al. Topical aqueous extract of Ephedra alata can improve wound healing in an animal model. Chin J Traumatol 2017; 20(2): 108-13.
[http://dx.doi.org/10.1016/j.cjtee.2016.10.004] [PMID: 28209447]
[137]
Puspasari A, Harijanti K, Soebadi B, Hendarti HT, Radithia D, Ernawati DS. Effects of topical application of propolis extract on fibroblast growth factor-2 and fibroblast expression in the traumatic ulcers of diabetic Rattus norvegicus. J Oral Maxillofac Pathol 2018; 22(1): 54-8.
[PMID: 29731557]
[138]
Mansouri E, Hardani A, Afzalzadeh MR, Amir Zargar A, Meamar Z. Combined effects of retinoic acid and hydro-alcoholic extract of Rosa damascena mill on wound in diabetic rats. Iranian journal of pharmaceutical research. Iran J Pharm Res 2016; 15(2): 583-9.
[PMID: 27642329]
[139]
Perini JA, Angeli-Gamba T, Alessandra-Perini J, Ferreira LC, Nasciutti LE, Machado DE. Topical application of Acheflan on rat skin injury accelerates wound healing: a histopathological, immunohistochemical and biochemical study. BMC Complement Altern Med 2015; 15(1): 203.
[PMID: 26122670]
[140]
Mulisa E, Asres K, Engidawork E. Evaluation of wound healing and anti-inflammatory activity of the rhizomes of Rumex abyssinicus J. (Polygonaceae) in mice. BMC Complement Altern Med 2015; 15(1): 341.
[PMID: 26423525]
[141]
Maurya H, Semwal M, Dubey SK. Pharmacological evaluation of Chrozophora tinctoria as wound healing potential in diabetic rat’s model. BioMed research international 2016.
[http://dx.doi.org/10.1155/2016/7475124]
[142]
Bhat KS, Vishwesh BN, Sahu M, Shukla VK. A clinical study on the efficacy of Panchavalkala cream in Vrana Shodhana w.s.r to its action on microbial load and wound infection. Ayu 2014; 35(2): 135-40.
[http://dx.doi.org/10.4103/0974-8520.146216] [PMID: 25558157]
[143]
Yadollah-Damavandi S, Chavoshi-Nejad M, Jangholi E, Nekouyian N, Hosseini S, Seifaee A, et al. Topical Hypericum perforatum improves tissue regeneration in full-thickness excisional wounds in diabetic rat model. Evidence-Based Complemen and Alter Med 2015.
[144]
Zhao Y, Yu J, Liu J, An X. The role of Liuwei Dihuang Pills and Ginkgo leaf tablets in treating diabetic complications. Evidence-Based Complementary and Alternative Medicine 2016.
[http://dx.doi.org/10.1155/2016/7931314]
[145]
Routes AE. Drug Absorption Distribution And Elimination; Pharmacokinetics 2019.
[146]
Bharath S. Pharmaceutical technology: Concepts and applications: Pearson Education India 2013.
[147]
Lopez FL, Ernest TB, Tuleu C, Gul MO. Formulation approaches to pediatric oral drug delivery: benefits and limitations of current platforms. Expert Opin Drug Deliv 2015; 12(11): 1727-40.
[http://dx.doi.org/10.1517/17425247.2015.1060218] [PMID: 26165848]
[148]
Bhagwat R, Vaidhya I. Novel drug delivery systems: An overview. Int J Pharm Sci Res 2013; 4(3): 970.

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