microbiological profile of infected diabetic foot ulcers

1032

© 2002 Diabetes UK.

Diabetic Medicine

,

19

, 1032–1035

Blackwell Science, Ltd

Letters

LettersLetters

Microbiological profile of infected diabetic foot ulcers

The microbiological profile of diabetic foot infections oftendemonstrates complex polymicrobial infection. We carriedout what we believe to be the largest survey (including a totalof 825 patients) for the microbiological profiles of mild ormoderate infected diabetic foot ulcers. The patients includedwere those who were enrolled in two phase-III clinical trials ofPexiganan (a topical peptide anti-infective agent) [1], had clin-ically diagnosed infected diabetic foot ulcers and were selectedfrom approximately 90 medical centres across the USA. Allpatients had mild or moderate infected foot ulcers withoutother obvious deep tissue or systemic infections, such asadvanced cellulitis, fascitis, osteomyelitis, lymphangitis, anabscess and bacteraemia. No patients included were hospital-ized or were under current antibiotic treatment for at least2 weeks prior to an ulcer culture collection. Tissue curettagewas used for obtaining the cultures from the wounds through-out this study [2]. A small tissue sample was scraped from thebase of the ulcer and placed in the transport medium for ship-ment to the test centre. The minimum inhibitory concentration(MIC) of antibiotics was determined in broth assays accordingto the National Committee for Clinical Laboratory Standards(NCCLS) protocols for all bacterial isolates [3].

The specimens were originally taken from 825 patients.Among those, 13 specimens were unculturable due to damageor lost during the shipment, and the remaining 812 specimenswere appropriately processed and cultured. About 90% ofcultures (from a total of 730 patients) were positive with at leastone microorganism identified. The average number of micro-organisms recovered was approximately 2.4 per wound. Ofthe infected diabetic foot ulcers 75% had multiple micro-organisms (25% of wound with one isolate, 33% with twoisolates, 21% with three isolates, 13% with four isolates and8% with five or more isolates). Our findings are generally inconsistent with most prior observations [2,4–7].

A total of 1817 isolates, including Gram-positive and Gram-negative aerobes, and anaerobes as well as fungi, were recov-ered from positive cultures (Table 1). Gram-positive aerobicbacteria were the dominant, comprising 68% of all isolates.Among these isolates, the most frequently recovered genus was

Staphylococcus

(645 isolates), which accounted for aboutone-third of all isolates, and next in occurrence were speciesof

Enterococcus

(254 isolates),

Streptococcus

(221 isolates), and

Corynebacterium

(85 isolates). The most frequently isolatedspecies was

S. aureus

(305 isolates); it accounted for 17% of allisolates, and was present in 42% of wounds that had a positiveculture.

Enterococcus faecalis

(211 isolates), found in 29% ofwounds, was the second most commonly isolated.

Streptococcusagalactiae

(125 isolates),

S. epidermidis

(111 isolates) and

S. haemolyticus

(43 isolates) were also frequently recovered.Only 11 isolates of

Streptococcus

group A species were recov-ered from 812 patients, suggesting that this species is not amajor causative species in mild to moderate diabetic foot ulcerinfections.

Gram-negative aerobic bacteria were less common in theulcers, accounting for 24% of all isolates. The ratio of Gram-positive aerobes to Gram-negative aerobes is approximately3:1 (1226:431), which is higher than in some earlier studies[2,6].

Pseudomonas aeruginosa

found in 58 ulcers was themost common Gram-negative species.

Escherichia coli

(50isolates),

Proteus mirabilis

(41 isolates), and

Enterobactercloacae

(27 isolates) were the next most frequent Gram-negativeaerobes identified. Species of

Enterobacteriaceae

family (251isolate) dominated among the Gram-negative bacteria,accounting for 58% of Gram-negative aerobes and 14% ofall isolates. In addition,

Acinetobacter

spp. (53 isolates) and

Stenotrophomonas maltophilia

(24 isolates) were also recoveredfrequently. Obligate anaerobes only represented a smallproportion in the wound isolates (6%).

Peptostreptococcus

spp.(36 isolates),

Prevotella

spp. (35 isolates), and

Bacteroides

spp.(28 isolates) were the three most common anaerobic generaisolated. The overall ratio of aerobe to anaerobe among allisolates was approximately 7:1. Obligate anaerobes were neverthe sole bacterial species isolated; they were always recoveredtogether with aerobes. The percentage of anaerobic speciesrecovered in our study was notably lower than in severalearlier reports [4,7]. The frequency of anaerobes recovered fromnon-limb or life-threatening diabetic foot ulcer infections is about25–45% [2,8]. The importance of anaerobes in diabetic footinfections remains unclear. In addition, 52 fungal isolates,most composed of

candida

spp. (43 isolates), were also recov-ered from the ulcers, but they accounted for only about 3% oftotal isolates.

We determined the

in vitro

susceptibility of 1308 bacterialisolates from infected diabetic foot ulcers to several classes ofantibiotics including

β

-lactams, macrolides, quinolones, andaminoglycosides.

Staphylococcus aureus

,

S. epidermidis

and

S. haemolyticus

exhibited a high frequency of resistance to theantibiotics tested. For example, 12% of

S. aureus

, 46% of

S. epidermidis

, and 45% of

S. haemolyticus

were oxacillin-resistant. High levels of resistance to erythromycin were foundin most species of Gram-positive bacteria.

Stenotrophomonasmaltophilia

isolates demonstrated the least susceptibility to theantibiotics tested in this study. The resistant profiles from thesetopical isolates are not different from other reports.

In conclusion, this study represents a comprehensivemicrobiological survey of mild or moderate infected diabeticfoot ulcer. As shown in this or other studies, the number andtype of potential microbiological pathogens in diabetic footinfections are large. Gram-positive aerobes, especially with

DME_696.fm 032 Wednesday, November 27, 2002 5:20 PM

Letters

1033


Diabetic Medicine

,

19

, 1032–1035

Organisms

IsolatesPercent in patients with positive cultures (730)No %

Gram-positive aerobesStaphylococcus aureus 305 16.8 42S. epidermidis 111 6.1 15S. haemolyticus 43 2.4 6S. simulans 28 1.5 4Other Staphylococcus spp. 158 8.7 22Group A Streptococcus 6 0.3 < 1Group B Streptococcus 125 6.9 17St. canis 30 1.7 4Other Streptococcus spp. 66 3.6 9Enterococcus faecalis 211 11.6 29Other enterococci 43 2.4 6Corynebacterium striatum 21 1.2 3Other Corynebacterium spp. 64 3.5 9Other Gram-positive aerobes 15 0.8 2Subtotal 1226 67.5

Gram-negative aerobesAcinetobacter calocaceticus 21 1.2 3Other Acinetobacter spp. 32 1.8 4Alcaligenes spp. 12 0.7 2Citrobacter spp. 20 1.1 3Enterobacter cloacae 27 1.5 4Other Enterobacter spp. 22 1.2 3Escherichia coli 50 2.8 7Klebsiella oxytoca 16 0.9 2K. pneumoniae 12 0.7 2Other Klebsiella spp. 11 0.7 2Morganella spp. 9 0.5 1Proteus mirabilis 41 2.3 6Other Proteus spp. 13 0.7 2Providencia spp. 9 0.5 1Serratia spp. 21 1.2 3Pseudomonas aeruginosa 58 3.2 8Other Pseudomonas spp. 18 1.0 3Stenotrophomonas maltophilia 24 1.3 3Other Gram-negative aerobes 15 0.8 2Subtotal 431 23.7

Gram-positive anaerobesPeptostreptococcus magnus 15 0.8 2Other Peptostreptococcus spp. 21 1.2 3Other Gram-positive anaerobes 3 0.2 < 1Subtotal 39 2.1

Gram-negative anaerobesBacteroides fragilis 15 0.8 2Other Bacteroides spp. 13 0.7 2Prevotella bivia 19 1 3Prevotella spp. 16 0.9 2Other Gram-negative anaerobes 6 0.3 < 1Subtotal 69 3.8

YeastCandida spp. 43 2.4 6Other fungal spp. 9 0.5 1Subtotal 52 2.8Total 1817 100

Table 1 Distribution of microorganisms recovered from diabetic foot wounds

DME_696.fm Page 1033 Wednesday, November 27, 2002 5:20 PM


Diabetic Medicine

,

19

, 1032–1035

1034

Letters

Staphylococcus

, remain a predominant species in diabetic footinfections. The data gathered from this study should provideuseful information for clinicians in selecting antibiotics forthe treatment of infected diabetic foot ulcers, although there isa debate whether antibiotics are always necessary in mild ormoderate cases.

Y. Ge, D. MacDonald, H. Hait, B. Lipsky*,M. Zasloff and K. Holroyd

Genaera Pharmaceuticals Inc., Plymouth Meeting, PA,and*Department of Medicine, University of Seattle

School of Medicine, Seattle, WA, USA

References

1 Lipsky BA, Litka PA, Zasloff M, Nelson K, the MSI-78 and 304 StudyGroup. Microbial eradication and clinical resolution of infecteddiabetic foot ulcers treated with topical MSI-78 vs oral ofloxacin.

37th ICAAC Abstract

1997; 74.2 Sapico FL, Witte JL, Canawati HN, Montgomerie JZ, Bessman AN.

The infected foot of the diabetic patient: quantitative microbiologyand analysis of clinical features.

Rev Infect Dis

1984;

6

: S171–176.3 National Committee for Clinical Laboratory Standards.

Methods forDilution Antimicrobial Susceptibility Tests for Bacteria That GrowAerobically

, 4th edn. Wayne, PA: National Committee for ClinicalLaboratory Standards, 1997.

4 Sims D, Keating SE, DeVincentis AF. Bacteriology of diabetic footulcers.

J Foot Surg

1984;

23

: 149–151.5 Wheat LJ, Allen SD, Henry M, Kernek CB, Siders JA, Kuebler T

et al.

Diabetic foot infections. Bacteriologic analysis.

Arch Intern Med

1986;

146

: 1935–1940.6 Axler DA. Microbiology of diabetic foot infections.

J Foot Surg

1987;

26

: S3–S6.7 Urbancic-Rovan V, Gubina M. Infection in superficial diabetic foot

ulcers.

Clin Infect Dis

1997;

25

: S184–S185.8 Fierer J, Daniel D, Davis C. The fetid foot: lower-extremity infections

in patients with diabetes mellitus.

Rev Infect Dis

1979;

1

: 210–217.

19LetterLettersLetters

Continuous internet-based activity monitoring provides a surrogate marker for nocturnal polyuria in persons with diabetes mellitus at high risk for foot ulceration

Nocturia is widely perceived to be a reliable symptom of poorglycaemic control in persons with diabetes mellitus [1,2]. Pro-longed poor glycaemic control is a prime precipitant of bothmicro- and macrovascular complications in diabetes mellitus.Included among the principal long-term complications ofprolonged hyperglycaemia are neuropathy, diabetic foot ulcers,lower extremity infections and amputations [3,4]. In the pres-ence of neuropathy, the prime precipitant of foot ulcerationincludes pressure and prolonged activity (cycles of stress) overthis area of pressure [5,6].

We have recently found that continuous monitoring ofpatients’ activity though specialized internet-based devices isuseful for identifying the magnitude and duration of activity inour patients at high risk for amputation [7]. In a study of just

such a population of United States veterans, we identified thatas many or more steps are taken in the home as they are in thecommunity, while only a small fraction of these patientsreported wearing their protective shoes while at home [8]. Ina subsequent analysis of this population, who were instructedto wear this activity monitor 24 h daily, we endeavoured toidentify whether increased nocturnal activity correlated wellwith reported nocturia.

In this population of 20 men, aged 64.6

±

1.8 years (mean

±

SEM

) with peripheral neuropathy and a mean 13.4

±

1.3 yearshistory of diabetes mellitus, a total of 35% responded that theyregularly took more than one nightly visit to the bathroomto urinate. Nocturnal activity (steps per 24-h period betweenmidnight and 05.00) was significantly greater in those patientswho reported more than one nightly bathroom visit(89.1

±

45.9 vs. 36.3

±

21.0 nightly steps;

P

= 0.039).The results of this brief analysis suggest that increased

nocturnal activity in persons with diabetes at high risk fordiabetic foot ulceration may be related to the presence of nocturia.The device utilized in this study allows not only the assessmentof the magnitude of activity but also the time at which theactivity occurred. Similar devices to the one used in this project arepresently commercially available (fitsense.com, stayhealthy.com).This feature, we believe, may ultimately allow clinicians tomonitor and dose activity just as one would dose a drug. Theability to monitor activity, we believe, may play a significantrole in diagnosis and motivation. The ability to dose activityaccurately may allow more precise modulation of cardiovascularfitness and post-surgical rehabilitation goals as well as, in ourinitial experience, the ability to limit periods of excessive activitywhich could lead to skin breakdown in our most high-riskpatients. The data gleaned in this analysis provide us with yetanother rationale for improved glucose control in thispopulation.

D. G. Armstrong and A. J. M. Boulton

Department of Surgery, Southern Arizona VeteransAffairs Medical Center, Tucson, AZ, USA and

Department of Medicine, Manchester Royal Infirmary,Manchester, UK

References

1 Keen H. Diagnosis of diabetes mellitus. In Alberti KGMM, DeFronzoRA, Keen H, Zimmet P eds.

International Textbook of DiabetesMellitus.

New York: John Wiley & Sons, 1992; 19–30.2 Wyngaarden JB, Smith LJJ, eds.

Cecil’s Textbook of Medicine

, 17thedn. Philadelphia: Saunders, 1985.

3 Lavery LA, Armstrong DG, Vela SA, Quebedeaux TL, Fleischli JG.Practical criteria for screening patients at high risk for diabetic footulceration.

Arch Intern Med

1998;

158

: 158–162.4 Boulton AJ, Vileikyte L. The diabetic foot: the scope of the problem [in

process citation].

J Fam Pract

2000;

49

: S3–8.5 Armstrong DG, Nguyen HC, Lavery LA, van Schie CH, Boulton AJM,

Harkless LB. Offloading the diabetic foot wound: a randomizedclinical trial.

Diabetes Care

2001;

24

: 1019–1022.6 Armstrong DG, Peters EJ, Athanasiou KA, Lavery LA. Is there a


Letters

1035


Diabetic Medicine

,

19

, 1032–1035

critical level of plantar foot pressure to identify patients at risk forneuropathic foot ulceration?

J Foot Ankle Surg

1998;

37

: 303–307.7 Armstrong DG, Boulton AJM. Activity monitors: should we begin

dosing activity as we dose a drug?

J Am Podiatr Med Assn

2001;

91

:152–153.

8 Armstrong DG, Abu Rumman PL, Nixon BP, Boulton AJM. Contin-uous activity monitoring in persons at high risk for diabetes-relatedlower extremity amputation.

J Am Podiatr Med Assoc

2001;

91

: 451–455.

19LetterLettersLetters

Alternative medicine recommendations to patients with Type 2 diabetes visiting health product shops and pharmacies

We read with interest the recent article by Dr E. Ryan [1] demon-strating that 44% of their patients with diabetes in Edmonton(Canada) took over-the-counter supplements and 31% weretaking ‘alternative medications’. Clearly, a considerable numberof diabetic patients are attracted to use alternative medicinesdespite the considerable extra cost of such treatment [2].

We were interested in exploring the recommendations madeto diabetic patients seeking advice on alternative treatmentsfor their illness. To do this we employed a moderately over-weight middle-aged actor to visit a number of pharmacies andalternative health product outlets (selected on a conveniencebasis). The actor visited 10 pharmacies and 15 alternativehealth product outlets over a 2-day period, and was debriefedby one of us after each visit. She played the part of a patientwith Type 2 diabetes, hypertension and high cholesterol levels,who had been advised of the need to start insulin treatmentto control hyperglycaemia. The actor also sought advice aboutwhether insulin treatment would still be necessary if she tookany of the recommended treatments. On each occasion thetype of treatment recommended, its cost and rationale for usewere recorded. The study was approved by the University ofAuckland Human Subjects Ethics Committee. As this was anexploratory study only, no power calculations were made.

Alternative medication was recommended in 12 of the 15alternative health product outlets, but only in three of the 10pharmacies visited (

P

< 0.02,

χ

2

test, comparing alternativehealth product outlets and pharmacies). Health productoutlets recommended a median number of five (range 0–9)products as suitable. A wide variety of medications wererecommended, but the most frequent were mineral supplementscontaining chromium and/or magnesium; a mixed preparationcalled

Glucon

containing gymnema, monordica, fenugreekand chromium (‘for the maintenance of normal blood glucoselevels’); vitamin B complexes; and a mixed preparation called

Lo-Chol

containing (amongst other things) lecithin, garlic,dandelion, evening primrose oil and fish oil (‘for loweringharmful LDL and the boosting of beneficial HDL’).

The monthly cost of the individual recommended productsranged from £1.68 (NZ$5) to £11.75 ($35), with the simplemineral supplements the cheapest and the mixed productsmore expensive. In answer to the query about the necessity of

starting insulin, referral to an alternative health practitioner (anaturopath) was recommended significantly more frequently(four pharmacies and eight health product outlets) than wasreferral to a conventional physician (three pharmacies and twohealth product outlets;

P

= 0.02, comparing the proportionof recommendations made to conventional and alternativepractitioners). Only one health product outlet suggested thatinsulin therapy might not be necessary, otherwise all establish-ments emphasized that the insulin should still be taken.

Our study suggests that a typical patient with Type 2diabetes is likely to be recommended a considerable range ofalternative medicine when visiting health product outlets. Thecosts of using such products over an extended period of timewould be substantial. A standard (government subsidized)prescription costs £5 (NZ$15) per item for 3 months, comparedwith the frequently recommended product

Glucon

at a costof £35 ($105) for 3 months. Both pharmacies and healthproduct shops were appropriately cautious in their recommen-dations about insulin therapy. Both encouraged the patientto seek expert advice, with referral to a naturopath beingpreferred to physician referral.

Many people with diabetes, particularly those with highereducational attainment, are attracted to the alternative healthmarket [3], and to the evidence-based, modern diabetes healthprofessional this can be a source of frustration. However, thecomplexity of modern management of diabetes and its associ-ated conditions, and the emphasis on self-management, maycontribute to the attraction of alternative medicine. Thisexploratory study was limited by the use of a single scenarioand the small number and range of establishments visited.However, it did demonstrate that there is a very active marketfor alternative medicine for people with diabetes. A wide rangeof products is available, and the market is closely linked to anetwork of alternative practitioners. Given the chronic natureof diabetes, it is likely to be a lucrative market, with the poten-tial to be very costly to patients. There is a need for futurestudies to determine the type of products being used, and howwidespread their use is. Diabetes health professionals need todiscuss with patients their use of alternative medicine.

K. J. Petrie and T. Cundy*

Department of Health Psychology and*Department ofMedicine, Faculty of Medicine & Health Sciences,University of Auckland, Auckland, New Zealand

References

1 Ryan EA, Pick ME, Marceau C. Use of alternative medicines indiabetes mellitus.

Diabet Med

2001;

218

: 242–245.2 Leese GP, Gill GV, Houghton GM. Prevalence of complementary

medicine usage within a diabetes clinic.

Pract Diabetes Int

1997;

14

:207–208.

3 Egede LE, Zheng D, Xiaobou Y, Silverstein MD. The prevalence andpattern of complementary and alternative medicine use in individualswith diabetes.

Diabetes Care

2002;

25

: 324–329.


microbiological profile of infected diabetic foot ulcers

Documents