REVIEW

CURRENT
OPINION Diabetic foot infections: recent literature
and cornerstones of management
Ilker Uçkay a,b, Karim Gariani c, Victor Dubois-Ferrière a, Domizio Suvà a,
and Benjamin A. Lipsky a,d

Purpose of review
Diabetes mellitus has reached pandemic levels and will continue to increase worldwide. Physicians and
surgeons should know to manage one of its most prevalent complications, the diabetic foot infection (DFI),
in a scientifically based and resource-sparing way. We performed a nonsystematic review of recent
scientific literature to provide guidance on management of DFIs.
Recent findings
Studies in the past couple of years provide data on which recommendations for diagnosing and treating
DFI are based, especially with validated guidelines and reviews of the microbiology and selected aspects
of the complex DFI problem. Recent literature provides approaches to prevention and studies support more
conservative surgical treatment. Unfortunately, there have been virtually no new therapeutic molecules,
antibiotic regimens, randomized trials, or surgical techniques introduced in the recent past; we briefly
discuss how this may change in the future.
Summary
Recent scientific evidence on DFI strongly supports the value of multidisciplinary and some new care
models, guideline-based management, more preventive approaches, and confirms several established
therapeutic concepts. In contrast, there has been almost no new substantial information regarding the
optimal antibiotic or surgical management in recent literature.
Keywords
antibiotic, diabetic foot infection, pathogens, surgery, treatment

INTRODUCTION estimated at 5.1%, whereas the prevalence among

&

In the beginning of this century, there were perhaps
175 million people worldwide with diabetes mellitus,
whereas by 2030 the projected number is 360 million
[1]. Diabetes is associated with many complications,
but foot disorders are now among the most common,
and the major cause of hospitalization. Although
very often an epiphenomenon of other underlying
problems, diabetic foot infections (DFIs) are frequent
in persons with diabetes and considerably diminish
&
the quality of life [2,3 ]. Moreover, diabetes is a well
established risk factor for various types of surgical site
infections [4], as well as for community-acquired
orthopaedic infections. In a recent study conducted
at Geneva University Hospitals, we retrieved records
for 2740 episodes of various types of orthopaedic
infections. Overall, in 659 (24%) of these cases the
patient was noted to have diabetes. Infections of the
foot were the most frequent type, but even excluding
these from the analysis diabetes was present in 17% of
cases of orthopaedic infections. By comparison, in
Geneva, the overall prevalence of diabetes is
our hospitalized adults was 13% [5 ]. In light of this
high rate of diabetes-related lower extremity infec-
tions, physicians and surgeons who care for these
patients must be aware of current recommendations
for prevention and treatment of DFI. To help provide
this information, we assembled authors who are
specialists in infectious diseases, orthopaedic surgery
and diabetes to conduct a nonsystematic review of
recent developments in this field and to provide
this update.
a
Service of Infectious Diseases, bOrthopedic Surgery Service, cService
of Diabetology and Endocrinology, Geneva University Hospitals and
Faculty of Medicine, University of Geneva, Switzerland and dDivision
of Medical Sciences, University of Oxford, Oxford, UK
Correspondence to Professor Benjamin A. Lipsky, MD, FACP, FIDSA,
FRCP, Division of Medical Sciences, University of Oxford, 79 Stone
Meadow, Oxford OX2 6TD, UK. Tel: +44 1865 559078;
e-mail: dblipsky@hotmail.com
Curr Opin Infect Dis 2016, 29:145–152
DOI:10.1097/QCO.0000000000000243

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Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.

Skin and soft tissue infections
KEY POINTS
 Multidisciplinary and multifaceted guidelines-based
approaches provide optimal outcomes.
 We still lack randomized trials regarding the best
duration and route of administration of antimicrobial
agents in diabetic foot soft tissue infections and/
or osteomyelitis.
 A conservative (antibiotic) nonamputation approach for
toe osteomyelitis is possible with long-term success up
to 60–70%.
 The basic principles of therapy, such as obtaining a
specimen for culture, selecting and refining antibiotic
therapy, rapidly undertaking needed surgical
interventions, ensuring adequate arterial perfusion, and
off-loading pressure, remain the keys to
good outcomes.
METHODOLOGY
We searched the medical literature using the PubMed
database with the Medical Subject Headings terms
‘diabetic foot’ and ‘infection’ for papers in the
English language. We concentrated on the manage-
ment of DFIs, rather than their pathophysiology. We
refer readers interested in further details on the epi-
demiology and risk factors [6,7], detailed reviews on
diagnosis [8], microbiology [6], or classification [9],
and the latest on management of underlying ischae-
&
mia [3 ], to recently published specific reviews and
the Infectious Diseases Society of America guidelines
[10].
TREATMENT
Glucose management for diabetic foot
infection patients
Although the number of articles regarding DFI
&
dramatically increases every year [3 ], surprisingly
Table 1. Proposed approach to perioperative glucose management of diabetic patients undergoing surgery for a foot infection
(adapted from [11–14])
Factors to consider
Current treatment for diabetes
Oral hypoglycaemic agents
Long-acting insulin analogues (e.g., determir, glargine)
Intermediate-acting insulin (e.g., neutral protamine)
Blood glucose target
Premeal level
Random levels
146 www.co-infectiousdiseases.com
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
few are concerned with glycaemia management
during the DFI episode. The goals for glycaemic
control, particularly for the perioperative period,
aim at avoiding patient morbidity, while promot-
ing infection control, optimizing colloid osmotic
pressure and electrolyte balance, preventing severe
hypoglycaemia or hyperglycaemia, and avoiding
ketoacidosis [11]. We found no prospective studies
of issues related to the value of glycaemic control
on the outcome of DFIs, but in the past 2 years
recommendations from authoritative sources sup-
port this approach. The American College of Phys-
icians and the American Diabetes Association
advocate attempting to keep the serum glucose
level in a range from 140 to 200 mg/dl (7.8–
11.1 mmol/l) for critically ill patients. For noncriti-
cally ill patients, including the majority of DFI
patients, they consider a preprandial blood glu-
cose level less than 140 mg/dl (<7.8 mmol/l), in
conjunction with random blood glucose values
less than 180 mg/dl (<10.0 mmol/l), adequate
[12,13].
In the context of sepsis or in the perioperative
period, patients often develop an insulin-resistant
state that requires higher insulin dosages. For
patients who normally only use oral hypoglycae-
mic agents, these should be discontinued 24 h
prior any surgery. This is especially important
for patients receiving therapy with metformin,
who must be advised to suspend this medication
in the preoperative period because of the risk of
developing lactic acidosis [13]. Sliding scale insu-
lin regimens without basal insulin should be
avoided, as they are associated with poor clinical
outcomes [14]. The preferred regimens are either
basal or bolus insulin algorithms, with supple-
mental or corrected doses of intravenous insulin
[11]. For patients taking intermediate acting insu-
lins, the dose should be reduced to 50% of their
usual dose on the morning of the surgery, and
short-acting insulin should be avoided [11,14]
(Table 1).
Recommended perioperative management
Stop 24 h before surgery
Usual dose in evening before surgery, then hold further doses
Reduce the dose to 50% of the usual dose the morning of surgery
<140 mg/dl (7.8 mmol/l)
<180 mg/dl (10.0 mmol/l)
Volume 29  Number 2  April 2016

Therapeutic surgery
Many DFIs require treatment with both medical and
surgical interventions, but there is currently limited
evidence on what constitutes optimal surgical treat-
&
ment [3 ]. Some type of surgery is necessary for
almost all acute, moderate, or severe infections,
especially those with evidence of necrotizing fascii-
tis. Similarly, most patients with associated septic
arthritis and a substantial proportion of those with
osteomyelitis (such as those with substantial
necrotic bone, involvement of the mid or hind foot,
or inadequate soft tissue cover) require surgery. A
recent study of diabetic foot osteomyelitis cases
treated surgically reported that those involving
the first metatarsal joint were less likely to heal than
those in other locations, such as the lesser toes [15].
Partial calcanectomy, despite a high-clinical failure
rate, may be considered for calcaneal osteitis, and
has a limited adverse impact in walking ability [16].
Available data suggest that for patients with foot
gangrene, a two-stage amputation (initial guillotine
with later revision) may lead to better stump healing
than a one-stage procedure [17 ].
&
Preventive surgery
The concept of preventive surgery for the diabetic
foot has been gaining momentum recently. In the
presence of flexible forefoot deformities, such as
claw or hammer toes, percutaneous toe flexor tenot-
omies appear to be effective in reducing ulceration,
with minimal risk of wound healing complications
[18,19]. Dorsiflexion of the ankle limited to less than
58 (equinuus deformity) restricts the leg from rolling
over the foot during the late stance phase of walking
and places excessive pressure on the plantar fore-
foot. A randomized controlled trial by Mueller and
colleagues [20] demonstrated that Achilles tendon
lengthening decreased plantar pressure over the
forefoot and reduced recurrence of neuropathic
ulceration of the plantar aspect of the forefoot in
patients with limited ankle dorsiflexion. In contrast,
Kim et al. [21] advocated that selective plantar fascia
release could have fewer complications, and pre-
ferred this technique before considering Achilles
tendon lengthening. Lastly, gastrocnemius reces-
sion (partial or complete release of the muscle) is
another technique reported to decrease plantar pres-
sure, thereby helping treat ulcers in the forefoot and
midfoot [18]. These surgical procedures should,
however, generally be avoided in patients with com-
plex situations. For example, in patients with
Charcot’s osteo-neuroarthropathy (especially with
infection), there is only fair evidence for any surgical
prophylaxis other than amputation. However, a
recent report on 20 cases found a high success rate
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Diabetic fo ot infections Uçkay et al.
FIGURE 1. Hammer toe with purulent discharge from
infected ulcer.
using a retrograde intramedullary hind foot arthrod-
esis nail [22].
Antimicrobial therapy
Moderately or severely infected diabetic foot
wounds, that is, those with evidence of purulent
secretions or at least two signs of inflammation (e.g.,
redness, warmth, induration, pain, or tenderness)
with extensive cellulitis or penetration below the
&
subcutaneous tissues (Fig. 1) [3 ], always require
antibiotic therapy. The hypothesis that some mildly
infected diabetic foot ulcers (superficial with <2 cm
of surrounding erythema) may be adequately
treated with appropriate wound care but without
antimicrobials is currently being tested in a large
randomized controlled trial (https://clinicaltrials.
gov/ct2/show/NCT01594762?term ¼ pexiganan&
rank ¼ 1).
Because of the difficulty in healing some ulcers,
many physicians and surgeons prescribe antibacte-
rial chemotherapy even for clinically uninfected
wounds [23] in hope of either accelerating healing
or avoiding active infection (by lowering the
‘bioburden’ of bacteria in the wound). However,
no published data support any clinical benefits for
this practice, which is accompanied by risk of
adverse treatment-related events, financial cost,
and risk of promoting antibiotic resistance. Experts
&&
from DFI committees [10,24 ] and the European
Wound Management Association [25] have strongly
recommended withholding topical or systemic anti-
biotic therapy in patients with a diabetic foot wound
that is clinically uninfected. Fortunately, there is
evidence that clinicians can be successfully taught
to reduce unnecessary antibiotics prescribing for
wounds. A recent large study in Sweden [26] showed
that providing web-based information on appropri-
ate ulcer care was associated with a significant
reduction (from 71% to 29%) of antibiotic prescrib-
ing for these wounds. Other methods to improve
www.co-infectiousdiseases.com 147
Skin and soft tissue infections

physicians’ antibiotic prescribing include having an

12 weeks after

12–92 days

26 weeks
active antimicrobial stewardship programme and

EOT
Follow-up

NA
interdisciplinary quality teams [27,28].

duration

48 h after enrolment

48 h after enrolment
Covering the pathogens

Not allowed beyond

Not allowed beyond

47% (various types)

Empiric antibiotic coverage for a DFI should virtu-

conservative
ally always include Staphylococcus aureus, the com-

0%; 100%
monest pathogen in most studies. Therapy should

Surgery,
be broadened to target Gram-negative pathogens in

type
severe infections, if the patient has failed to respond
to prior narrower-spectrum antibiotic therapy, or in

75%; 86%

71%; 78%

36%; 64%
countries (especially in Asia and Africa) where

81%
remission
Gram-negative pathogens are more common [29].

Clinical
In these latter cases, it is especially important to
obtain optimal specimens for culture and to initiate

group); 10 days
90 days (antibiotic
an empiric regimen different from the failing one.

(surgery group)

Mean 6.1 days

Anaerobes may be involved, particularly in wounds

11–12 days
Duration of

(median)
that are deeper, more chronic, or accompanied by

(1–30)
therapy

39 days
necrosis or ischaemia. Our recent review has shown
that anaerobes are relatively infrequent in DFIs, and
it remains unclear whether their presence leads to
&
more severe manifestations [30 ]. There is also con-

Intravenous

100%

100%

100%
0%
Table 2. Selected recent studies on antibiotic therapy for diabetic foot infections (adapted from [23])
troversy as to whether or not DFIs caused by methi-
treatment
cillin-resistant S. aureus (MRSA) are associated with
worse outcomes than those caused by other patho-

DFI, diabetic foot infection; DFO, diabetic foot osteomyelitis; EOT, end of therapy; NA, not applicable or not available.
gens. We addressed this issue with a nonsystematic

surgery, antibiotics,
Antibiotic regimen

ertapenem (466)
literature search that retrieved 48 papers published
or agent (number

prolonged (25);

Tigecycline (476);

ertapenem (33)

Ceftaroline (201)
Tigecycline (53);
Oral antibiotics,
&
from 1999 to 2013 [31 ]. Notwithstanding the sub-
of patients)

stantial limitations of the available literature, we short (27)

found no evidence that MRSA DFI infections were
associated with any worse outcomes. In the era of
molecular microbiology, we now know that there
are usually many more isolates that are undetected
osteomyelitis)

osteomyelitis)
Osteomyelitis

by standard culture techniques [32]. What we still

No (all had

No (all had
excluded?

do not understand, however, is what clinical signifi-

cance these isolates play. Recent metagenomic stud-
Yes

DFI (201) hospitalized Yes

ies have revealed the interplay among bacterial

Randomized-controlled trials with at least some intravenous therapy
hospitalized, then

hospitalized, then

communities in various environments, including

(number enrolled)

Randomized controlled DFO (52) initially

Randomized controlled DFI (955) initially

DFI, that produce specific clinical ‘syndromes’ or

Infection type

outpatient

outpatient

phenotypic diseases. This rapidly emerging research

Randomized controlled DFO (118)

area will almost certainly provide more insights on

Observational (prospective or retrospective) studies

the potential association of the skin (and gastroin-

Randomized-controlled trials of oral therapy only

testinal) microbiome of DFI patients [6,33].

observational study
trial (substudy)
Study design

Which antibiotics?
Retrospective

Patients with a severe infection generally require

trial

trial

parenteral antibiotic therapy, at least initially. Most

b-lactam antibiotics achieve relatively low tissue
levels when administered orally. However, agents
Lipsky (2014) [37]
Lauf (2014) [36 ]

Lauf (2014) [36 ]

&

&

such as clindamycin, fluoroquinolones, linezolid,

(2014) [35 ]
&&
Lázaro-Martinez
author, year

rifampin, tetracyclines, and cotrimoxazole have

Reference:

shown good oral bioavailability, as well as adequate

penetration in bone, biofilm, and perhaps necrotic
&
tissue [3 ,6]. With this available arsenal, almost all

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Table 3. Suggested potential antibiotic regimens for DFIsa (authors’ personal choice; simplified summary adapted from [24 ])
Infection severity Empirical therapy
Mild Amoxicillin/clavulanate 1 g
t.i.d.
S. aureus, Streptococci Gram-positive coverage
MRSA
Gram-negative rods No Gram-negative coverage
needed
P. aeruginosa No pseudomonal coverage
needed
Moderate
Gram-positive and Amoxicillin/clavulanate 1 g
negative coverage t.i.d. or I.V. 1.2 g t.i.d.
Severe and clinical sepsis
Gram-positive and Piperacillin/tazobactam I.V.
negative coverage, 4.5 g t.i.d.
anaerobic coverage
b.i.d, twice daily; I.V., intravenous; MRSA, methicillin-resistant Staphylococcus aureus; t.i.d., three times daily.
a
Doses are adapted for patients without renal insufficiency.
DFI could potentially be treated orally, and with a
large, multicentre trial comparing intravenous to
oral antibiotic therapy (https://clinicaltrials.gov/
ct2/show/NCT00974493?term ¼ OVIVA&rank ¼ 1)
just concluding, we will have robust data on this
issue. Several previous randomized trials in DFI have
shown no superiority for any particular antibiotic
& &&
agent or route of administration [3 ,6,23]. A
Cochrane systematic review and meta-analysis pub-
lished in 2015 analysed publications on systemic
&&
antibiotics for treating DFI [34 ]. A total of
20 included trials (of which 18 were industry-spon-
sored) with 3791 patients did not show that any
particular agent or regimen was superior to others,
except that tigecycline was significantly less effec-
tive and associated with more adverse effects than
&&
ertapenem ( vancomycin) [34 ]. Table 2 summar-
izes data from antibiotic trials for DFI published in
the last 2 years that compare various molecules.
Table 3 summarizes, in a simplified manner, the
personal choices of the authors, as adapted from
the guidance of the International Working Group
&&
on the Diabetic Foot [24 ].
Knowing the potential for poor outcomes, many
clinicians have tended to treat DFIs with a long
duration of antibiotic therapy. Data from recent
comparative trials have shown that 1–2 weeks
is sufficient for most soft tissue infections, and
4–6 weeks appears adequate in those with (unre-
&
sected) infected bone [3 ,6]. Retrospective reviews
over the past two decades have demonstrated that
about two-thirds of selected patients with diabetic
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Diabetic fo ot infections Uçkay et al.
&&
Targeted therapy Alternative agents
According to the pathogens Cotrimoxazole 960 mg b.i.d.
Clindamycin 600 mg t.i.d. Amoxicillin/clavulanate 1 g t.i.d.
Linezolid 600 mg b.i.d. Clindamycin 600 mg t.i.d.
Cotrimoxazole 960 mg b.i.d.
Ciprofloxacin 500–750 mg Cotrimoxazole 960 mg b.i.d.
b.i.d.
Ciprofloxacin 500–750 mg No oral alternatives; I.V. drugs
b.i.d.
According to the pathogens Levofloxacin 500–750 mg b.i.d.
Piperacillin/tazobactam I.V. 4.5 g t.i.d.
According to the pathogens Imipenem I.V. 500–750 mg qad and
vancomycin I.V. 1 g b.i.d. if MRSA
likely
foot osteomyelitis can achieve remission with anti-
biotic therapy alone (i.e., without bone resection). A
recent randomized trial found that treatment with
only antibiotic therapy (given for 90 days) gave
similar clinical outcomes to treatment with conser-
vative surgery (removal only of the infected bone)
along with just a short course of antibiotic therapy
[35 ]. Another randomized trial compared a 6-week
against 12-week course of antibiotic therapy, with-
out concomitant surgery, for diabetic foot osteo-
&
myelitis [38 ] and also found similar outcomes.
Topical antibiotics and antimicrobial
dressings
Last year, we reviewed the role of antibiotics, includ-
ing topical agents, in healing wounds and treating
DFI [23]. We found that relatively few studies of
topical antimicrobial therapy for DFI have been
published, and these employed a variety of anti-
biotics, such as mupirocin, bacitracin, polymyxin
B, neomycin, and gentamicin. In the published
studies, topical antimicrobial agents were usually
applied only in mild DFI, and along with other types
of wound care, making it difficult to assess their
clinical benefits. Lastly, a recent randomized trial on
stump wounds examined the value of adding a
gentamicin–collagen sponge to systemic antibiotic
therapy after a minor foot amputation [39]. The
patients receiving the gentamicin–collagen sponge
had a significantly shorter (by almost 2 weeks)
median wound healing time compared with those
www.co-infectiousdiseases.com 149
Skin and soft tissue infections

Table 4. Summary of findings from recent literature, and possible future developments, in the management of diabetic foot
infections (adapted from [3 ]) &

Research field Recent literature reports Possible future developments

Pathogens Emergence of multidrug-resistant pathogens, Optimized infection control measures; increase

Microbiological diagnosis
Antibiotic agents
Route of administration
Duration of antibiotic therapy
including MRSA and ESBLs
Investigation of skin and wound microbiomes,
including of diabetic foot ulcers
Few antibiotic combination tested
Evidence suggesting equivalence of bioavailable
oral and intravenous therapy
Available studies (mostly retrospective) suggest
shorter durations for skin (and possibly bone)
infections effective
in broad-spectrum antibiotic use for Gram-
negative resistant pathogens; screening and
decolonization
Genetic analysis; whole-genome sequencing;
further investigation of the wound microbiome
Testing of combinations and new antibiotic
agents
More oral therapies, except for resistant
pathogens; new topical antimicrobial agents
More prospective trials to determine needed
duration of therapy for soft tissue and for
bone infections

Surgical approach More conservative (limited) treatment of toe and
forefoot osteomyelitis; limited amputations
Revascularization More percutaneous angioplasty and distal
bypasses, including infragenicular
Management Clinical guidelines based on systematic reviews;
multidisciplinary teams, especially including
podiatry; clinical pathways; some behavioural
sciences
Adjunctive treatments Limited data on hyperbaric oxygen or negative
pressure wound therapies for infection
Conservative surgery will become more
widespread; more preventive surgery
Revascularization procedures will be more
available; possible stem-cell therapy to
improve vascularity
National guidelines; WHO guidelines; WHO
programmes; clinical pathways
Potential use of stem cell, bacteriophage
therapies

Scientific publications Current management based mostly on case series More prospective randomized trials, multicentre
and retrospective studies studies, and evidence-based (e.g., Cochrane)
meta-analyses; implementation of available
guidelines

ESBL, extended-spectrum b-lactamase producing organisms; MRSA, methicillin-resistant Staphylococcus aureus.

who did not. Our view is that available studies do
not yet clarify in which patients topical antimicro-
bials (either alone or combined with systemic anti-
biotics) may be beneficial. While awaiting ongoing
studies, we prefer avoiding topical antibiotic agents
that are also available for systemic therapy, as this
may induce development of antibiotic resistance.
&
[41 ]. One case–control study, including 82 diabetic
foot ulcer patients, demonstrated a significantly
shorter hospital stay, and fewer surgical visits, in
NPWT patients with antimicrobial installation com-
pared with NPTW without [42], but this same group
more recently found that instillation of saline was as
effective as an antiseptic [43].

Negative-pressure wound therapy Stem cell therapy

Negative-pressure wound therapy (NPWT) is widely
used for accelerating healing of various types of
wounds. The last 2 years have been productive in
&
terms of scientific papers on ulcers [3 ]. A recent
systematic review identified only four randomized
trials; these suggested that NPWT results in more
effective and faster diabetic foot ulcer healing than
standard care [40]. NPWT can now be combined
with instillation of various agents, including anti-
septics, to reduce the wound ‘bioburden’, but the
effectiveness of these methods is currently unclear
With the current suboptimal outcomes of treating
diabetic foot ulcers, researchers are seeking novel
approaches, such as stem cell therapy. Recent stud-
ies found that autologous bone marrow cell trans-
plantation in patients with an ischaemic diabetic
foot ulcer increased leg perfusion and reduced the
risk of amputations [44,45]. Studies using umbilical
cord stem cells [45] have also reported encouraging
results and adipose tissue stem cells have also been
successfully harvested from abdominal subcu-
taneous fat [46]. Although stem cell therapy shows

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encouraging results regarding angiogenesis, it cur-
rently has no proven benefit in treating infection.
CONCLUSION
Our review of the literature published in the past
2 years on infectious complications of the diabetic
foot has provided some new information regarding
selected aspects of this common and potentially
devastating problem. Improved glycaemic control
in these patients, especially those undergoing
surgery, is likely helpful. We discussed issues con-
cerning how to select the most appropriate empiri-
cal antibiotic therapy, as well as the role of
anaerobes and MRSA in DFIs. Although antibiotic
therapy is necessary for almost all infections, it is not
sufficient; clinicians must also ensure the patient
gets proper podiatric care, including pressure off-
loading. Unfortunately, recent reviews have
reported that almost no new therapeutic molecules,
antibiotic regimens, or surgical techniques have
been found in the recent past. Table 4 presents a
view of current and possible future research in the
field of DFI.
Acknowledgements
The authors are indebted to the Department of Ortho-
pedic Surgery and the Laboratory of Microbiology. They
also thank Benjamin Kressmann for his help.
Financial support and sponsorship
None.
Conflicts of interest
K.G., V.D.F., and D.S. declare no conflicts of interest.
B.A.L. has served as a consultant to Innocoll, Forest,
Cubist, Merck, and Pfizer. I.U. has received research
donation from Innocoll for another project not related
to this manuscript.
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management of medical and surgical patients with type 2 diabetes. Diabetes
Care 2013; 36:2169–2174.
15. Cecilia-Matilla A, Lázaro-Martı́nez JL, Aragón-Sánchez J, et al. Influence of
the location of nonischemic diabetic forefoot osteomyelitis on time to
healing after undergoing surgery. Int J Low Extrem Wounds 2013;
12:184–188.
16. Walsh TP, Yates BJ. Calcanectomy: avoiding major amputation in the pre-
sence of calcaneal osteomyelitis: a case series. Foot (Edinb) 2013; 23:130–
135.
17. Tisi PV, Than MM. Type of incision for below knee amputation. Cochrane
& Database Syst Rev 2014; 4:CD003749.
The Cochrane review found only three studies with a total of 309 patients and
concluded that there was no evidence that any one type of incision for below knee
amputation is better than any other, but a two-stage procedure is associated with
better stump healing for patients with wet gangrene.
18. Cychosz CC, Phisitkul P, Belatti DA, et al. Current concepts review: pre-
ventive and therapeutic strategies for diabetic foot ulcers. Foot Ankle Int
2015; 11:1–10.
19. Rasmussen A, Bjerre-Christensen U, Almdal TP, et al. Percutaneous flexor
tenotomy for preventing and treating toe ulcers in people with diabetes
mellitus. J Tissue Viability 2013; 22:68–73.
20. Mueller MJ, Sinacore DR, Hastings MK, et al. Effect of Achilles tendon
lengthening on neuropathic plantar ulcers. A randomized clinical trial. J Bone
Joint Surg Am 2003; 85:1436–1445.
21. Kim JY, Hwang S, Lee Y. Selective plantar fascia release for nonhealing
diabetic plantar ulcerations. J Bone Joint Surg Am 2012; 94:1297–1302.
22. Siebachmeyer K, Boddu M, Bilal A, et al. Outcome of one-stage correction of
deformities of the ankle and hindfoot and fusion in Charcot neuroarthropathy
using a retrograde intramedullary hindfoot arthrodesis nail. Bone Joint J 2015;
97:76–82.
23. Abbas M, Uçkay I, Lipsky BA. In diabetic foot infections antibiotics are to treat
infection, not to heal wounds. Expert Opin Pharmacother 2015; 16:821–
832.
24. Lipsky BA, Aragón-Sánchez J, Diggle M, et al. IWGDF guidance on the
&& diagnosis and management of foot infections in persons with diabetes.
Diabetes Metab Res Rev 2015. [Epub ahead of print]
In this, the third update of the International Working Group on the Diabetic Foot
guidance document on infection of the diabetic foot, this multidisciplinary inter-
national committee of experts produced a comprehensive, exhaustively referenced
review of the infectious aspects of the diabetic foot problem. It has several helpful
tables and a clinically useful management algorithm.
25. Gottrup F, Apelqvist J, Bjarnsholt T, et al. EWMA document: antimicrobials
and nonhealing wounds. Evidence, controversies and suggestions. J Wound
Care 2013; 22:1–9.
26. Oien RF, Forssell HW. Ulcer healing time and antibiotic treatment before and
after the introduction of the registry of ulcer treatment: an improvement project
in a national quality registry in Sweden. BMJ Open 2013; 3:003091.
27. Grover ML, Nordrum JT, Mookadam M, et al. Addressing antibiotic use for
acute respiratory tract infections in an academic family medicine practice. Am
J Med Qual 2013; 28:485–491.
28. Vinnard C, Linkin DR, Localio AR, et al. Effectiveness of interventions in
reducing antibiotic use for upper respiratory infections in ambulatory care
practices. Popul Health Manag 2013; 16:22–27.
29. Hatipoğlu M, Mutluoğlu M, Uzun G, et al. The microbiologic profile of diabetic
foot infections in Turkey: a 20 year systematic review. Eur J Clin Microbiol
Infect Dis 2014; 33:871–878.
www.co-infectiousdiseases.com 151
Skin and soft tissue infections
30. Charles PG, Uçkay I, Kressmann B, et al. The role of anaerobes in diabetic foot
& infections. Anaerobe 2015; 34:8–13.
The role of obligate anaerobes in foot infections in persons with diabetes
has been debated for decades. This nonsystematic review of the literature,
bolstered by extensive data from the authors own medical centre,
suggest that anaerobic infections are relatively uncommon (in developed
western countries) and adequate debridement (and, when needed,
revascularization) is as important as correct antibiotic therapy for good
outcomes.
31. Zenelaj B, Bouvet C, Lipsky BA, et al. Do diabetic foot infections
& with methicillin-resistant Staphylococcus aureus differ from those
with other pathogens? Int J Low Extrem Wounds 2014; 13:263–
272.
The authors from Geneva University Hospitals address the issue of the importance
of MRSA as a pathogen in DFIs. Their nonsystematic review of the literature
and the experience at their own hospital over 4 years suggests that there is
little evidence to support that MRSA infections are associated with worse out-
comes.
32. Spichler A, Hurwitz B, Armstrong DG, et al. Microbiology of diabetic foot
infections: from Louis Pasteur to ‘Crime Scene Investigation’. BMC Med
2015; 13:2.
33. Lavigne JP, Sotto A, Dunyach-Remy C, et al. New molecular techniques to
study the skin microbiota of diabetic foot ulcers. Adv Wound Care 2015;
4:38–49.
34. Selva Olid A, Solà I, Barajas-Nava LA, et al. Systemic antibiotics for
&& treating diabetic foot infections. Cochrane Database Syst Rev 2015;
9:CD009061.
The conclusions of this systematic review and meta-analysis of systemic
antibiotic therapy for DFIs are that data from the 20 included trials (with a
total of 3791 patients) are limited by the heterogeneity and risk of bias.
They found no evidence that any one antibiotic agent or regimen was
superior to another, but they discussed the differences in both
outcomes and adverse events with various classes of agents used in published
studies.
35. Lázaro-Martı́nez JL, Aragón-Sánchez J, Garcı́a-Morales E. Antibiotics
&& versus conservative surgery for treating diabetic foot osteomyelitis: a
randomized comparative trial. Diabetes Care 2014; 37:789–
795.
After many retrospective cases series suggested that successful treatment of
diabetic foot osteomyelitis with antibiotic therapy and no surgical resection of bone
were possible, this is the first prospective trial on this important issue. The small,
randomized study had several problems, but concluded that antibiotic therapy and
surgical treatment had similar rates of healing rates and short-term complications in
patients with nonischaemic, nonnecrotizing neuropathic forefoot ulcers compli-
cated by osteomyelitis.
152 www.co-infectiousdiseases.com
Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved.
36. Lauf L, Ozsvár Z, Mitha I, et al. Phase 3 study comparing tigecycline and
& ertapenem in patients with diabetic foot infections with and without osteo-
myelitis. Diagn Microbiol Infect Dis 2014; 78:469–480.
In this well designed, large trial, treatment with tigecycline compared with erta-
penem (with or without vancomycin) was associated with both worse clinical
outcomes and higher rates of adverse effects for patients with both soft tissue and
bone infections. Tigecycline should probably be relegated to the bottom of the list
of agents for treating DFIs.
37. Lipsky BA, Cannon CM, Ramani A, et al. Ceftaroline fosamil for treatment of
diabetic foot infections: the CAPTURE study experience. Diabetes Metab Res
Rev 2014; 31:395–401.
38. Tone A, Nguyen S, Devemy F, et al. Six-week versus twelve-week antibiotic
& therapy for nonsurgically treated diabetic foot osteomyelitis: a multicenter
open label controlled randomized study. Diabetes Care 2015; 38:302–307.
What appears to be the first randomized controlled trial found that rates of
resolution of diabetic foot osteomyelitis were similar in patients treated without
surgery, but with one of these two durations of antibiotic therapy. This suggests
treatment for longer than 6 weeks is probably not needed for these patients.
39. Varga M, Sixta B, Bem R, et al. Application of gentamicin-collagen sponge
shortened wound healing time after minor amputations in diabetic patients: a
prospective, randomised trial. Arch Med Sci 2014; 10:283–287.
40. Guffanti A. Negative pressure wound therapy in the treatment of diabetic foot
ulcers: a systematic review of the literature. J Wound Ostomy Continence
Nurs 2014; 41:233–237.
41. Dale AP, Saeed K. Novel negative pressure wound therapy with instillation
& and the management of diabetic foot infections. Curr Opin Infect Dis 2015;
28:151–157.
A review of the limited available literature concluded that treatment with negative
pressure wound therapy with irrigation is a promising treatment for DFIs, but we
need more prospective trials, testing different solutions.
42. Kim PJ, Attinger CE, Steinberg JS, et al. The impact of negative-pressure
wound therapy with instillation compared with standard negative-pressure
wound therapy: a retrospective, historical, cohort, controlled study. Plast
Reconstr Surg 2014; 133:709–716.
43. Kim PJ, Attinger CE, Oliver N, et al. Comparison of outcomes for normal saline
and an antiseptic solution for negative-pressure wound therapy with instilla-
tion. Plast Reconstr Surg 2015; 136:657–664.
44. Hanselman AE, Lalli TA, Santrock RD. Topical review: use of fetal tissue in foot
and ankle surgery. Foot Ankle Spec 2015; 3:1–10.
45. Li XY, Zheng ZH, Li XY, et al. Treatment of foot disease in patients with type 2
diabetes mellitus using human umbilical cord blood mesenchymal stem cells:
response and correction of immunological anomalies. Curr Pharm Des 2013;
19:4893–4899.
46. Zuk PA, Zhu M, Mizuno H, et al. Multilineage cells from human adipose tissue:
implications for cell-based therapies. Tissue Eng 2001; 7:211–227.
Volume 29  Number 2  April 2016