Prevalence and interrelationships of foot ulcer, risk-factors and antibiotic resistance in foot ulcers in diabetic populations: A systematic review and meta-analysis

Table 1 Characteristics of the included studies

Ref.	Study type	Male: Female ratio	Type 2 diabetes mellitus/Type 1 diabetes	Duration of Diabetes	HbA1c%	Ulcer description	Follow-up months
Quilici et al[21]	Cross-sectional study	68 males and 32 females	T2DM	22% had for less than five yr; 24% had from 5-10 yr; 17% had from 10-15 yr; 16% had from 15-20 yr; 21% had for >20 yr	-	75% patients had Grade 4 ulcers; 20% had Grade 3 ulcers; 5% had Grade 2 ulcers	-
Commons et al[26]	Prospective study	60% male and 40% females	All patients had T1DM, except of 7 patients	-	Median value was 8.8%	Diabetic patients with ulcers or foot infections were referred	14 mo
Barwell et al[28]	Combination of literature review	-	T1DM and T2DM	-	-	Standardized using validated classifications schemes such as the University of Texas rating, SINBAD or IWGDF PEDIS	-
Roth-Albin et al[24]	Retrospective cohort study	67.9% were males	-	-	-	Ulcer sizes > 1 cm2	52 wk
Fitzgerald et al[30]	Retrospective study	4:4	-	Average disease duration 22 yr	-	Active foot-ulcer with a wound swab taken	15 mo
Kathirvel et al[22]	Retrospective study	74.6% males and 25.33% females	T2DM	< 5 yr - 40%; 5-10 yr - 34%; 10-15 yr - 17%; 15-20 yr - 7.3%; > 20 yr - 1.3%	6%-7%	Categorized into necrotic/non-necrotic; ulcers based on signs of infection	-
Xie et al[16]	Hospital-based retrospect study	230 males and 158 females	T2DM	-	-	Severity of ulcer was assessed by Wagner-Meggit classification system	-
Dwedar et al[41]	Observational prospective study	48 males (57%) and 32 females (43%)	-	5-32 yr	-	Graded according to Wagner’s grade	-
Abbas et al[45]	Literature review	-	T2DM	-	-	Classified on the basis of wound debridement, pressure off-loading, glycemic control, surgical interventions, and occasionally other adjunctive measures	-
Oliveira et al[46]	Epidemiological, retrospective and descriptive study	27 males and 30 females	-	-	-	Infected ulceration was associated with germs present in the community	-

International Working Group on the Diabetic Foot provides guideline for preventing and managing diabetic foot disease. Type 2 diabetes mellitus is a chronic medical condition, which occurs when the cell of the body resist effect of insulin for driving glucose to the blood cells. Type 1 diabetes mellitus is a condition when pancreas produce low or lack of insulin as required by the body. IWGDF: International Working Group on the Diabetic Foot; T2DM: Type 2 diabetes mellitus; T1DM: Type 1 diabetes mellitus; HbA1c: Hemoglobin A1c.

Table 2 Objective of the study, findings and outcome data

Ref.	Methodology/Approach	Findings	Outcome
Quilici et al[21]	Cross-sectional study	Prevalence of amputation was 42% due to the previous use of antimicrobials. Risk of amputation was 26% for patients who had less compliant with the diabetes treatment	Highlight factors for the management patients with diabetic foot infection
Commons et al[26]	Prospective study was conducted among patients with diabetic foot infections, enrolled in Royal Darwin Hospital, were selected. The relation with Pseudomonas aeruginosa and methicillin resistant Staphylococcus aureus was also determined	P. aeruginosa and Methicillin resistant S. aureus infections were cured by long-term courses of antibiotics and increased hospital stay	Prevalence of diabetic foot ulcer is directly and significantly related to the best bed days
Barwell et al[28]	A literature review was conducted	Antibiotic and antimicrobial resistance of Gram positive organisms occurred as a main challenge in the treatment of diabetic foot infection	Provides guideline as empirical evidence to support clinicians
Roth-Albin et al[24]	Retrospective cohort study	35 out of 40 patients were healed in 52 weeks. 7.1% underwent amputation and 8.9% died before receiving any kind of treatment	Healing rates significantly improved by proper and continued care
Fitzgerald et al[30]	Retrospective exploratory study	Diabetes and Cardiovascular disease/peripheral-vascular disease was identified in 2 and 6 patients, respectively. 28 patients had foot ulcers and RA. Inflicted patients were treated with antirheumatic drugs and steroids	Inaccurate diagnosis of ulcer infection leads to failure of microbiological analysis
Kathirvel et al[22]	150 patients’ clinical examination, clinical history and microbiological profile were prospectively examined	99 patients were isolated from MDRO. MDRO risk factors include; previous antibiotic usage, retinopathy, polymicrobial culture, presence of ulcer, antibiotic usage, ulcer size, history of amputation, peripheral vascular disease, neuropathy, and necrotic ulcer	MDRO prevalence was high among diabetic patients with foot ulcers
Xie et al[16]	Retrospective study was conducted using 207 bacteria from diabetic foot infections. Microbial and clinical information was also collected	Gram negative bacteria were found to be more as compared to gram positive bacteria with, Staphylococcus and Enterobacteriaceae to be the most dominant	The antibiotic sensitivity and bacterial profile of diabetic foot ulcers varied with their types and grades
Dwedar et al[41]	80 patients with diabetic foot infections were prospectively studied	Gram negative bacteria were more common. Vancomycin was found to be the best against gram-positive bacteria; whereas, colistin, imipenem and amikacin were effective against gram-negative bacteria	Knowledge regarding antibiotic sensitivity is required for future treatment of diabetic foot ulcers
Abbas et al[45]	Non-systematic research	Antibiotic therapy is necessary for several clinically infected wounds	Antibiotic therapies should be used for treatment
Oliveira et al[46]	Descriptive, retrospective and epidemiological study was used	65% of cases suffered amputations. Staphylococci was the most common bacteria type. Three patients were found to be enterobacteria and second was, Staphylococci	Clindamycin and cephalexin were most resistant to bacteria

Infectious Diseases Society of America is a medical association which represents healthcare professional who are expert in treating infectious diseases. Rheumatoid Arthritis is an autoimmune disabling infection. It causes pain, swelling and inflammation in joints and other body organs. Multi-drug resistant organisms bacteria that is resistance to various antibiotics. IDSA: Infectious Diseases Society of America; RA: Rheumatoid arthritis; MDRO: Multi-drug resistant organisms.

Table 3 Description of studies causative agents from diabetic foot ulcer

Ref.	Total no of enrolled patients	Number of patients with isolated strains/ with multiple strains n(%)	Number of microorganisms, n (%)
			Gram positive							Gram negative					Fungus
			Aerobes						Ananerobes	Aerobes				Ananerobes
			Methicillin-sensitive Staphylococcus aureus (MSSA)	Methicillin-resistant Staphylococcus aureus. (MRSA)	Other Staphyloccus sp (Staphylococcus species)	Streptocccus sp	Enterococcus sp	Other Gram positive		Enterobacteriaceac members	Pseudomonas sp	Acinetobacter sp	Other gram negative sp
Quilici et al[21]	100	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Commons et al[26]	177	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Barwell et al[28]	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Roth-Albin et al[24]	40	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Fitzgerald et al[30]	28	-	+++	-	-	-	-	-	++	-	-	-	-	-	-
Kathirvel et al[22]	150	-	-	-	-	-	-	17.9%	-	-	-	-	69.89%	-	-
Xie et al[16]	405	95.8%	43.2%, 41/95	-	65.2%, 62/95	-	20.0%, 19/95	45.9%, 95/207	-	73.2%, 82/112	-	-	54.1%, 112/207	-	10.7%
Dwedar et al[41]	80	77	11.4%	(10.1%	46.8%	-		27.7%	-	-	10.8%	-	56.08%	8.1%	-
Abbas et al[45]	-	-	-	-	-	-	-	-	-	-	-	-	-	-	-
Oliveira et al[46]	66	-	22.7%	-	4.5%	-	-	-	-	-	-	-	-	-	-

-: No mention in literature; ++: The total may be over 100% this is because of mixed infections; percentage values are calculated from cases with isolated stains; +++: Approximate number. MSSA: Methicillin susceptible Staphylococcus aureus (bacteria that is not resistant to some antibiotics); MRSA: Methicillin resistant Staphylococcus aureus (Gram-positive bacteria that causes various infections in the body).