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Epidemiology of diabetic foot infections in a reference tertiary hospital in India

Abstract

Introduction

The present study attempts to examine the microbial profile and antibiotic susceptibility of diabetic foot infections in the intensive care unit of a tertiary referral centre for diabetic foot. As part of the study, we also attempted to find the prevalence of blaNDM-like gene among carbapenem-resistant gram negative infections.

Methodology

A prospective study of 261 patients with diabetic foot infections was performed during the period between January 2014 and June 2014.

Results

A total of 289 isolates were obtained from 178 tissue samples from 261 patients, 156 (59.7%) males and 105 (40.2%) females, with a mean age of 58 years (-15 years), having diabetic foot infection. No growth was seen in thirty eight (17.6%) tissue samples. Out of the total samples, 44.3% were monomicrobial and 55.7% were polymicrobial. Gram negative pathogens were predominant (58.5%). Seven of the total isolates were fungal; 0.7% showed pure fungal growth and 1.7% were mixed, grown along with some bacteria. The most frequently isolated bacteria were Staphylococcus aureus (26.9%), followed by Pseudomonas aeruginosa (20.9%). Of the 58.5% gram negative pathogens, 16.5% were Enterobacteriaceae resistant to carbapenems. Among these isolates, 4 (25%) were positive for blaNDM-like gene. Among the rest, 18.6% were carbapenem-resistant Pseudomonas, among which 4 (36.3%) were blaNDM. Among the Staphylococci, 23.7% were methicillin-resistant Staphylococcus aureus.

Conclusions

Our results support the recent view that gram negative organisms, depending on the geographical location, may be predominant in DFIs. There is an increase in multidrug-resistant pathogens, especially carbapenem resistance and this is creeping rapidly. We need to be more judicious while using empiric antibiotics.

Keywords:
Diabetic foot infection; blaNDM; MRSA

Introduction

Foot ulcers and other foot problems are a major cause of morbidity and mortality in people with Diabetes mellitus.11 Kucan JO, Robson MC. Diabetic foot infections: fate of the contralateral foot. Plast Reconstr Surg. 1986;77:439-441. Diabetic foot infections (DFIs) are the leading cause of hospitalization for diabetic patients worldwide and in developing countries like India, it accounts for 20% of hospital admissions.22 Goldstein EJ, Citron DM, Nesbit CA. Diabetic foot infections: bacteriology and activity of 10 oral antimicrobial agents against bacteria isolated from consecutive cases. Diabetes Care. 1996;19:638-641.,33 Shankar EM, Mohan V, Premalatha G, Srinivasan RS, Usha AR. Bacterial etiology of diabetic foot infections in South India. Eur J Int Med. 2005;16:567-570. DFI is a multifactorial process and three factors predispose to tissue damage, namely neuropathy, peripheral vascular disease, and susceptibility to infection whenever there is a direct injury to the foot at risk.44 Caputo GM, Cavanagh PR, Ulbrecht JS, Gibbons GW, Karchmer AW. Assessment and management of foot diseases in patients with diabetes. N Engl J Med. 1994;331:854-860.

5 Vagholkar KR, Shirabhatti RGB. The diabetic foot. Bombay Hosp J. 1994;36:197-203.
-66 Delbridge L, Appleberg M, Reeve TS. Factor associated with development of foot lesions in diabetic. Surgery. 1983;93:78-82. DFIs are usually polymicrobial, caused by aerobic gram positive cocci like Staphylococcus aureus, gram negative bacilli (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa), and anaerobes. Proper management of these infections needs appropriate antibiotic selection.77 Slovenkai MP. Foot problems in diabetes. Med Clin North Am. 1998;82(4):949-971. Empirical treatment is based on the pathogens and the susceptibility pattern seen in the community where the hospital is located.

Beta-lactam antibiotics are the most commonly used antibiotics for bacterial infections.88 Kotra LP, Samama J, Mobashery S. Beta-lactamases and resistance to beta lactam antibiotics. In: Lewis K, Slayers AA, Taber HW, Wax RG, eds. Bacterial Resistance to Antimicrobials. New York: Marcel Decker; 2002:123–160. However, the accelerated emergence of antibiotic resistance to these groups of drugs among the prevalent pathogens is the most serious threat to the management of such infections, especially carbapenem resistance. These isolates are usually multidrug resistant, which further complicate the scenario.

There is a recent emergence of the NDM metallo-beta-lactamase (MBL) encoding genes among different enterobacterial species and also in non-fermenters like P. aeruginosa and Acinetobacter baumannii in various parts of world including India.99 Yong D, Toleman MA, Giske CG, et al. Characterization of a new metallo-b-lactamase gene, blaNDM-1, and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother. 2009;53:5046-5054.

10 Shanthi M, Sekar U, Kamalanathan A, Sekar B. Detection of New Delhi metallo beta lactamase-1 (NDM-1) carbapenemase in Pseudomonas aeruginosa in a single centre in southern India. Indian J Med Res. 2014;140:546-550.
-1111 Kumarasamy KK, Toleman MA, Walsh TR, et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis. 2010;10:597-602. In fact, India and Pakistan are the main reservoirs of blaNDM-like carrying Enterobacteriaceae.1111 Kumarasamy KK, Toleman MA, Walsh TR, et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis. 2010;10:597-602. There is paucity of data on MBL-producing organisms carrying blaNDM-like gene from diabetic foot infections. Taking this into account, we studied the microbial profile and susceptibility pattern of diabetic foot infections in patients with Type 2 Diabetes mellitus to guide empiric therapy for diabetic foot infections in our hospital and the occurrence of blaNDM-like carbapenemase gene among carbapenem-resistant gram negative pathogens.

Materials and methods

Study type

A prospective study was performed on 261 diabetic patients with foot ulcers over a period of six months from January 2014 to June 2014. The study was conducted at a tertiary care hospital in Mumbai, India.

Study population

All patients with type 2 diabetes (irrespective of age and sex) who were hospitalized for surgical management of lower-extremity wounds from January 2014 till June 2014 were considered for the study. Their informed consent was obtained and demographic details, duration of lower-limb lesion, duration of diabetes, and type of empiric therapy were documented from their medical records. A deep tissue specimen was obtained from the wounds during surgery and sent for bacterial and fungal cultures.

Specimen collection

After surgical debridement of the slough and necrotic tissue over the wound in the operation theatre, the wound was washed thoroughly with normal saline; a deep tissue specimen of approximately 0.5 × 0.5 cm was taken from the wound bed. The specimen was collected in a sterile container soaked with normal saline and was transported to our microbiology laboratory without delay for further processing.

Specimen processing

Part of the sterile deep tissue specimen was crushed or ground with a sterile mortar and pestle in the biosafety cabinet. The crushed specimen was subjected to gram staining and was streaked on 5% sheep blood agar (SBA), MacConkey agar (MA), and Saboraud's Dextrose agar (SDA) for fungal culture. After inoculation, the SBA was kept in a candle jar and along with MA, it was kept in an incubator at 37 °C. Bacterial isolates and yeast-like fungus identification and susceptibility test was performed using VITEK 2 Compact automated culture system (bioMeriux, France). Commercial I+ IE (imipenem+ imipenem/EDTA) disc from Himedia, Mumbai, India was used for EDTA disc synergy test. All carbapenem resistant Enterobacteriaceae were tested for metallobetalactamase production. Modified Hodge test (MHT) was performed for all Enterobacteriaceae isolates resistant to carbapenems by Vitek 2 according to CLSI guidelines and EDTA disc synergy test was done for the detection of metallo-β-lactamase production for all gram negative isolates. ESBL production was confirmed by ceftazidime and ceftazidime/clavulunic acid disc synergy test and detection of AmpC β-lactamases was performed as follows.

AmpC detection methods

The isolates were screened for presumptive AmpC production by testing their susceptibility to cefoxitin (30 µg) using Kirby Bauer disc diffusion method and interpreted according to the CLSI guidelines.1212 Clinical Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing. M100-S24. Vol 34(1); 2014. All the isolates with an inhibition zone diameter of less than 18 mm were labelled as screen positive.

A lawn culture of E. coli ATCC 25922 was prepared on MHA plate. A sterile disc of 6 mm moistened with 20 µL of sterile saline was kept and several colonies of test organism were inoculated on this disc. A cefoxitin disc was placed next to this disc (almost touching) on the inoculated plate. The plates were incubated overnight at 37 °C. A flattening or indentation of the cefoxitin inhibition zone in the vicinity of the disc was considered a positive test.1313 Barua T, Shariff M, Detection ST. Characterization of AmpC B-Lactamases in Indian Clinical Isolates of Escherichia coli, Klebsiella pneumoniae and Klebsiella oxytoca. Univ J Microbiol Res. 2013;1(2):15-21.

PCR technique for detection of blaNDM

Total DNAs of the different bacterial isolates were extracted by alkaline lysis and PCR to detect blaNDM-like gene was performed as described by Poirel et al.1414 Poirel L, Walsh TR, Cuvilliera V, Nordmann P. Multiplex PCR for detection of acquired carbapenemase genes. Diagn Microbiol Infect Dis. 2011;70:119-123.

Results

A total of 216 diabetic patients with foot ulcers admitted to our hospital were studied during the 6 months study period from January 2014 to June 2014. Out of the 261 patients, 156 [59.7%] were males and 105 [40.2%] females of mean age 58 years (±15 years) with a DFI. Majority of the DFIs were Grade III (49.1%) (Table 1).

Table 1
Infections and depth of diabetic foot lesions.

A total of 289 isolates were obtained from 178 tissue samples. No growth was seen in thirty eight (17.6%) tissue samples. Distribution of the microorganisms in tissue samples is shown in Table 2. Monomicrobial infection was seen in 44.3% cases. Among the bacterial isolates, a total of 117 (41.5%) gram positive pathogens and 165 (58.5%) gram negative pathogens were isolated.

Table 2
Distribution of samples according the number of different bacterial species isolated from deep tissue (n = 178).

From the 165 gram negative isolates, 102 (61.8%) belonged to family Enterobacteriaceae. Among the Enterobacteriaceae isolated, Escherichia coli was found to be most common followed by Klebsiella pneumoniae (Table 3). Seven of the total isolates were fungal, of which 0.7% showed pure fungal growth and 1.7% were mixed, grown along with some bacteria. The fungal isolates corresponded to Candida albicans (2), Candida tropicalis (2), Candida spp. (1), Aspergillus fumigatus (1) and Rhodotorula sp.

Table 3
Bacterial pathogens in diabetic foot infection.

Piperacillin-tazobactam and cefoperazone sulbactam were the most frequently used empiric antibiotics (68%) among DFI patients. The antibiotics used were of broad spectrum primarily because our hospital is a tertiary referral centre for diabetic foot infections and hence, we get many admissions from smaller setups and nursing homes.

Out of 76 isolates, 18 (23.7%) were methicillin resistant S. aureus (MRSA). S aureus (MSSA +MRSA) strains were 100% sensitive to Vancomycin, Teicoplanin, and Linezolide (Fig. 1). The next common gram positive organism was Enterococcus faecalis and 11% (4 out of 36) were VRE (Vancomycin resistant Enterococcus) strains.

Fig. 1
Susceptibility pattern of Staphylococcus aureus.

E. coli and K. pneumoniae were the most frequent Enterobacteriaceae isolated. Their susceptibility pattern is shown in Figs. 2 and 3. Colistin was the most effective agent against enterobacterial isolates, followed by aminoglycosides and beta-lactam/beta-lactamase inhibitor combinations. Two (7.4%) of the 27 Klebsiella isolates were resistant to colistin. E. coli isolates were 100% sensitive to colistin.

Fig. 2
Susceptibility pattern of E. coli.

Fig. 3
Susceptibility pattern of Klebsiella pneumoniae.

Among the Enterobacteriaceae, sixteen isolates (16.8%) were resistant to carbapenems (Table 4). Nine of the 16 (56.2%) carbapenem resistant strains were MHT positive and 7 of the 16 isolates were positive for MBL detection by EDTA disk synergy test (EDS). All 16 isolates were studied for molecular characterization for blaNDM-like gene. Four of the seven carbapenem-resistant K. pneumoniae and one of the 3 carbapenem-resistant E. coli isolates were positive for blaNDM-like gene. All the isolates positive for blaNDM like gene were positive by EDS but only one Klebsiella isolates harbouring blaNDM-like gene was positive by MHT (Table 4).

Table 4
Phenotypic detection of resistance mechanisms in beta-lactam resistance Enterobacteriaceae (n: 95).

Among the gram negative isolates, 63 were non-fermenters being P. aeruginosa the most frequent (n = 59[93.6%]). Eleven (18.6%) P. aeruginosa isolates were carbapenem resistant strains. Four (36.3%) of the 11 carbapenem resistant isolates were positive for blaNDM-like gene, all 4 were positive by EDS. Fifteen percent (9/59) of the P. aeruginosa, were resistant to colistin. There were isolated two A. baumannii cases and both were carbapenem resistant, blaNDM positive, and susceptible only to colistin and tigecycline (Fig. 4).

Fig. 4
Susceptibility pattern of P. aeruginosa.

Outcome of patients with DFI

Amputation of the affected part was done in 120 (55.5%) of the patients, 85 (39.3%) had major debridement done, and the remainder (5.2%) of the patients underwent minor debridement and medical management. Among patients carrying carbapenem-resistant gram negative pathogens, 2 patients died. In one case, the isolate corresponded K. pneumoniae and the other to A. baumannii. Both carbapenem resistant isolates harboured blaNDM-like. The Klebsiella isolate was colistin resistant as well.

Discussion

Currently, 50.8 million Indians have diabetes. Projections indicate that India will have the largest number of diabetic patients by the year 2030AD.1515 Viswanathan V. Epidemiology of diabetic foot and management of foot problems in India. Int J Low Extremity Wounds. 2010;9(3):122-126. Diabetic foot infections are the most frequent complication requiring hospitalization.33 Shankar EM, Mohan V, Premalatha G, Srinivasan RS, Usha AR. Bacterial etiology of diabetic foot infections in South India. Eur J Int Med. 2005;16:567-570.,1616 Lavery LA, Armstrong DG, Wunderlich RP, Mohler MJ, Wendel CS, Lipsky BA. Risk factors for foot infections in individuals with diabetes. Diabetes Care. 2006;29:1288-1293. Microbial profiles of diabetic foot infections are widely studied and differ in different regions across India and the world. In our study, gram negative bacteria were more common isolates in DFI, similar to many studies performed in India.1717 Tiwari S, Pratyush DD, Dwivedi A, Gupta SK, Rai M, Singh SK. Microbiological and clinical characteristics of diabetic foot infections in northern India. J Infect Dev Ctries. 2012;6(4):329-332.,1818 Viswanathan V, Jasmine JJ, Snehalatha C, Ramachandran A. Prevalence of pathogens in diabetic foot infection in South Indian type 2 diabetic patients. J Assoc Phys India. 2002;50:1013-1016. In contrast, gram positive organisms predominate the causatives in the western part of the world.1919 Lipsky BA, Pecoraro RE, Wheat LJ. The diabetic foot: soft tissue and bone infection. Infect Dis Clin North Am. 1990;4:409-432.,2020 Citron DM, Goldstein EJC, Merriam CV, Lipsky BA, Abramson MA. Bacteriology of moderate to severe diabetic foot infections and in vitro activity of antimicrobial agents. J Clin Microbiol. 2007;45:2819-2828. When line listing the individual microorganisms, S. aureus was on top, followed by P. aeruginosa, similar to other studies from same region.2121 Chincholokar DA, Pal RB. Study of fungal and bacteriological infections of the diabetic foot. Indian J Pathol Microb. 2002;45:15-72.,2222 Mohanasoundaram KM. The microbial profile of diabetic foot infections. J Clin Diagn Res. 2012;6:409-412.S. aureus was the most frequent pathogen (28%, 42/150), followed by P. aeruginosa (24%, 36/150) in the study by Shanthi et al.1010 Shanthi M, Sekar U, Kamalanathan A, Sekar B. Detection of New Delhi metallo beta lactamase-1 (NDM-1) carbapenemase in Pseudomonas aeruginosa in a single centre in southern India. Indian J Med Res. 2014;140:546-550.E. coli was the most common pathogen isolated followed by S. aureus in a study from North India, but in other studies P aeruginosa has been reported most frequently.33 Shankar EM, Mohan V, Premalatha G, Srinivasan RS, Usha AR. Bacterial etiology of diabetic foot infections in South India. Eur J Int Med. 2005;16:567-570.,1717 Tiwari S, Pratyush DD, Dwivedi A, Gupta SK, Rai M, Singh SK. Microbiological and clinical characteristics of diabetic foot infections in northern India. J Infect Dev Ctries. 2012;6(4):329-332. Fungal pathogens and their role in DFI is less frequently studied. A study by Chellan et al.,2323 Chellan G, Shivprakash S, Ramaiyar SK, et al. Spectrum and prevalence of fungi infecting deep tissues of lower-limb wounds in patients with type 2 diabetes. J Clin Microbiol. 2010;48(6):2097-2102. revealed that there is a high prevalence (27.9%) of fungal infection in deep tissues of diabetic lower extremity wounds with Candida parapsilosis topping the list. Fungal infections accounted for 9% of the total isolates in a study by Bansal et al.2424 Bansal E, Garg A, Bhatia S, Attri AK, Chander J. Spectrum of microbial flora in diabetic foot ulcers. Indian J Pathol Microbiol. 2008;51:204-208.Candida tropicalis was the most common fungal isolate in their study. In contrast, we observed lower prevalence of fungal infections in our study.

There were observed lower MRSA rates compared to other studies from India where incidence of MRSA has been reported as high as 66%.2525 Banoo S, Shubha DS, Shashidhar V, Venkatesha D. Bacterial and clinical profile of diabetic foot patients. Ann Trop Med Public Health. 2012;59:69-73. Our study also revealed the predominant polymicrobial nature (55.7%) of infections. Monomicrobial infections were seen only in 44.3% cases. Other studies have revealed contrasting results with monomicrobial infections being more predominant. A study by Tiwari et al.1616 Lavery LA, Armstrong DG, Wunderlich RP, Mohler MJ, Wendel CS, Lipsky BA. Risk factors for foot infections in individuals with diabetes. Diabetes Care. 2006;29:1288-1293. showed that monomicrobial infections cases (43.5%, 27/62) were more than polymicrobial infections (35.5%, 22/62). In another study, equal number of polymicrobial and monomicrobial infections were reported (44.4%).2626 Sekhar SM, Vyas N, Unnikrishnan MK, Rodrigues GS, Mukopadhyay C. Antimicrobial susceptibility pattern in diabetic foot ulcer: a pilot study. Ann Med Health Sci Res. 2014;4(5):742-745. A study from South India found that monomicrobial infections (56%) were more predominant than polymicrobial infections (44%).2727 Sughandhi P, Prasanth DA. Bacteriological profile of diabetic foot infections. Int J Innov Res Sci Eng Technol. 2014;3:14688-14692.

Carbapenems are the mainstay in the treatment for multidrug-resistant gram negative bacteria; however, a rising number of carbapenemases (and thus, resistance) to this group of drugs is increasingly being reported from different parts of the world.2828 Gadepalli R, Dhawan B, Kapil A. A clinico-microbiological study of diabetic foot ulcers in an Indian tertiary care hospital. Diabetes Care. 2006;29:1727-1732. Metallo-beta-lactamase have been described previously in P. aeruginosa isolates from diabetic foot infections.2929 Vinodkumar CS, Hiresave S, Kandagal GB, Bandekar GN. Metallo-β lactamase producing Pseudomonas aeruginosa and its association with diabetic foot. Indian J Surg. 2011;73(4):291-294. NDM is the latest in the armamentarium of carbapenemases. NDM1 (New Delhi metallo-beta-lactamase) was first identified in isolates from a Swedish patient of Indian origin in 2008.99 Yong D, Toleman MA, Giske CG, et al. Characterization of a new metallo-b-lactamase gene, blaNDM-1, and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother. 2009;53:5046-5054. NDM producers have been described in studies from various parts of the world; although, many reports seem to originate from the Indian subcontinent.1111 Kumarasamy KK, Toleman MA, Walsh TR, et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis. 2010;10:597-602.,3030 Lascols C, Hackel M, Marshall SH, et al. The increasing prevalence and the dissemination of NDM-1 metallo-b-lactamase in India: data from the SMART study (2009). J Antimicrob Chemother. 2011;66(9):1992-1997.

However, there is paucity of data with respect to prevalence of NDM among isolates from DFIs in India. Khan et al. have reported NDM producing Enterobacter cloacae and Klebsiella pneumoniae strains isolated in two patients with diabetic foot ulcers from India.3131 Khan AU, Nordmann P. NDM-1-producing enterobacter cloacae and Klebsiella pneumoniae from diabetic foot ulcers in India. J Med Microbiol. 2012;61(3):454-456. Samant et al. have, for the first time, described Providencia rettgeri strains harbouring blaNDM-like in 4 patients with diabetic foot ulcers from India.3232 Samant SA, Marathe N, Vaishampayan A. Detection of blaNDM-1 gene in Providencia rettgeri isolated from diabetic foot ulcers of four patients from India. Int J Pharm Bio Sci. 2015;6(3):B125-B130. In our study, we found the presence of blaNDM-like in nonfermenters like Pseudomonas and Acinetobacter as well as in E. coli and K. pneumoniae.

With the current local microbiological and antibiogram data, cefoperazone/sulbactam or piperacillin/tazobactam with clindamycin was the suggested as the empiric antibiotic of choice for DFI with escalation to carbapenem (meropenem) with teicoplanin depending upon the culture sensitivity report.

Due to resource constrains we looked only for the blaNDM-like genes. However, its worth looking into the prevalence of other carbapenemase genes like KPC, IMP, VIM etc. In one short project for CRE screening in our hospital we found an increased prevalence of KPC like genes in K. pneumoniae isolated from stool samples.(unpublished data)

Conclusion

To the best of our knowledge, this study has dealt with perhaps the largest data in the world related to diabetic foot infections for studying the pathogen spectrum along with an attempt to study the prevalence of blaNDM-like gene. This study goes on to indicate that in a tertiary diabetic foot referral centre, polymicrobial gram negative infections are more predominant in DFIs. The study has also demonstrated the emergence of difficult-to-treat gram negatives as almost one fifth of the gram negatives. Therefore, the authors believe it is now highly recommended to have strict antimicrobial stewardship programmes and restrict unnecessary use of broad spectrum antibiotics to curb the menace of antibiotic resistance.

Brief summary

Already known:

Gram negative bacteria are more common than gram positive bacteria in DFI cases in India. Monomicrobial infections are more predominant than polymicrobial infections in most studies. NDM prevalence in DFI cases has been demonstrated by few studies.1313 Barua T, Shariff M, Detection ST. Characterization of AmpC B-Lactamases in Indian Clinical Isolates of Escherichia coli, Klebsiella pneumoniae and Klebsiella oxytoca. Univ J Microbiol Res. 2013;1(2):15-21.

What this study adds:

We handled a larger data pool for carbapenem-resistant bacteria in DFI cases than most studies. Polymicrobial infections (54%) were found to be more predominant than monomicrobial infections (44.3%) in DFI cases. Lower rate of MRSA among gram positive bacteria. Found the presence of blaNDM-like in nonfermenters like Pseudomonas and Acinetobacter as well as in E. coli and pneumoniae.

References

  • 1
    Kucan JO, Robson MC. Diabetic foot infections: fate of the contralateral foot. Plast Reconstr Surg 1986;77:439-441.
  • 2
    Goldstein EJ, Citron DM, Nesbit CA. Diabetic foot infections: bacteriology and activity of 10 oral antimicrobial agents against bacteria isolated from consecutive cases. Diabetes Care. 1996;19:638-641.
  • 3
    Shankar EM, Mohan V, Premalatha G, Srinivasan RS, Usha AR. Bacterial etiology of diabetic foot infections in South India. Eur J Int Med. 2005;16:567-570.
  • 4
    Caputo GM, Cavanagh PR, Ulbrecht JS, Gibbons GW, Karchmer AW. Assessment and management of foot diseases in patients with diabetes. N Engl J Med. 1994;331:854-860.
  • 5
    Vagholkar KR, Shirabhatti RGB. The diabetic foot. Bombay Hosp J. 1994;36:197-203.
  • 6
    Delbridge L, Appleberg M, Reeve TS. Factor associated with development of foot lesions in diabetic. Surgery 1983;93:78-82.
  • 7
    Slovenkai MP. Foot problems in diabetes. Med Clin North Am. 1998;82(4):949-971.
  • 8
    Kotra LP, Samama J, Mobashery S. Beta-lactamases and resistance to beta lactam antibiotics. In: Lewis K, Slayers AA, Taber HW, Wax RG, eds. Bacterial Resistance to Antimicrobials New York: Marcel Decker; 2002:123–160.
  • 9
    Yong D, Toleman MA, Giske CG, et al. Characterization of a new metallo-b-lactamase gene, blaNDM-1, and a novel erythromycin esterase gene carried on a unique genetic structure in Klebsiella pneumoniae sequence type 14 from India. Antimicrob Agents Chemother 2009;53:5046-5054.
  • 10
    Shanthi M, Sekar U, Kamalanathan A, Sekar B. Detection of New Delhi metallo beta lactamase-1 (NDM-1) carbapenemase in Pseudomonas aeruginosa in a single centre in southern India. Indian J Med Res. 2014;140:546-550.
  • 11
    Kumarasamy KK, Toleman MA, Walsh TR, et al. Emergence of a new antibiotic resistance mechanism in India, Pakistan, and the UK: a molecular, biological, and epidemiological study. Lancet Infect Dis. 2010;10:597-602.
  • 12
    Clinical Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing. M100-S24 Vol 34(1); 2014.
  • 13
    Barua T, Shariff M, Detection ST. Characterization of AmpC B-Lactamases in Indian Clinical Isolates of Escherichia coli, Klebsiella pneumoniae and Klebsiella oxytoca. Univ J Microbiol Res. 2013;1(2):15-21.
  • 14
    Poirel L, Walsh TR, Cuvilliera V, Nordmann P. Multiplex PCR for detection of acquired carbapenemase genes. Diagn Microbiol Infect Dis. 2011;70:119-123.
  • 15
    Viswanathan V. Epidemiology of diabetic foot and management of foot problems in India. Int J Low Extremity Wounds. 2010;9(3):122-126.
  • 16
    Lavery LA, Armstrong DG, Wunderlich RP, Mohler MJ, Wendel CS, Lipsky BA. Risk factors for foot infections in individuals with diabetes. Diabetes Care. 2006;29:1288-1293.
  • 17
    Tiwari S, Pratyush DD, Dwivedi A, Gupta SK, Rai M, Singh SK. Microbiological and clinical characteristics of diabetic foot infections in northern India. J Infect Dev Ctries. 2012;6(4):329-332.
  • 18
    Viswanathan V, Jasmine JJ, Snehalatha C, Ramachandran A. Prevalence of pathogens in diabetic foot infection in South Indian type 2 diabetic patients. J Assoc Phys India. 2002;50:1013-1016.
  • 19
    Lipsky BA, Pecoraro RE, Wheat LJ. The diabetic foot: soft tissue and bone infection. Infect Dis Clin North Am. 1990;4:409-432.
  • 20
    Citron DM, Goldstein EJC, Merriam CV, Lipsky BA, Abramson MA. Bacteriology of moderate to severe diabetic foot infections and in vitro activity of antimicrobial agents. J Clin Microbiol. 2007;45:2819-2828.
  • 21
    Chincholokar DA, Pal RB. Study of fungal and bacteriological infections of the diabetic foot. Indian J Pathol Microb. 2002;45:15-72.
  • 22
    Mohanasoundaram KM. The microbial profile of diabetic foot infections. J Clin Diagn Res. 2012;6:409-412.
  • 23
    Chellan G, Shivprakash S, Ramaiyar SK, et al. Spectrum and prevalence of fungi infecting deep tissues of lower-limb wounds in patients with type 2 diabetes. J Clin Microbiol 2010;48(6):2097-2102.
  • 24
    Bansal E, Garg A, Bhatia S, Attri AK, Chander J. Spectrum of microbial flora in diabetic foot ulcers. Indian J Pathol Microbiol. 2008;51:204-208.
  • 25
    Banoo S, Shubha DS, Shashidhar V, Venkatesha D. Bacterial and clinical profile of diabetic foot patients. Ann Trop Med Public Health. 2012;59:69-73.
  • 26
    Sekhar SM, Vyas N, Unnikrishnan MK, Rodrigues GS, Mukopadhyay C. Antimicrobial susceptibility pattern in diabetic foot ulcer: a pilot study. Ann Med Health Sci Res. 2014;4(5):742-745.
  • 27
    Sughandhi P, Prasanth DA. Bacteriological profile of diabetic foot infections. Int J Innov Res Sci Eng Technol. 2014;3:14688-14692.
  • 28
    Gadepalli R, Dhawan B, Kapil A. A clinico-microbiological study of diabetic foot ulcers in an Indian tertiary care hospital. Diabetes Care. 2006;29:1727-1732.
  • 29
    Vinodkumar CS, Hiresave S, Kandagal GB, Bandekar GN. Metallo-β lactamase producing Pseudomonas aeruginosa and its association with diabetic foot. Indian J Surg. 2011;73(4):291-294.
  • 30
    Lascols C, Hackel M, Marshall SH, et al. The increasing prevalence and the dissemination of NDM-1 metallo-b-lactamase in India: data from the SMART study (2009). J Antimicrob Chemother. 2011;66(9):1992-1997.
  • 31
    Khan AU, Nordmann P. NDM-1-producing enterobacter cloacae and Klebsiella pneumoniae from diabetic foot ulcers in India. J Med Microbiol 2012;61(3):454-456.
  • 32
    Samant SA, Marathe N, Vaishampayan A. Detection of blaNDM-1 gene in Providencia rettgeri isolated from diabetic foot ulcers of four patients from India. Int J Pharm Bio Sci. 2015;6(3):B125-B130.

Publication Dates

  • Publication in this collection
    Apr-Jun 2018

History

  • Received
    27 Jan 2016
  • Accepted
    12 Sept 2017
Sociedade Brasileira de Microbiologia USP - ICB III - Dep. de Microbiologia, Sociedade Brasileira de Microbiologia, Av. Prof. Lineu Prestes, 2415, Cidade Universitária, 05508-900 São Paulo, SP - Brasil, Ramal USP 7979, Tel. / Fax: (55 11) 3813-9647 ou 3037-7095 - São Paulo - SP - Brazil
E-mail: bjm@sbmicrobiologia.org.br