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39. van Asten SAV, Mithani M, Peters EJG, La Fontaine
J, Kim PJ, Lavery LA. Complications during treatment of diabetic foot osteomyelitis. Diabetes Res Clin
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40. Tone A, Nguyen S, Devemy F, Topolinski H, Valette
M, Cazaubiel M, etal. Six-week versus twelve-week
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B, Lipsky BA, Uçkay I.Remission in diabetic foot
infections: duration of antibiotic therapy and other
possible associated factors. Diabetes Obes Metab.
2019;21:244–51.
42. Gariani K, Pham R-R, Kressmann B, etal. Three versus
six weeks of antibiotic therapy for diabetic foot osteomyelitis: a prospective, randomized, non- inferiority
pilot trial. Clin Infect Dis. 2021;73(7):e1539–45.
43. Waibel F, Berli M, Cantanzaro S, Sairanen K, Schöni
M, Boni T, etal. Optimization of the antibiotic management of diabetic foot infections: protocol for two
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44. Dudareva M, Kumin M, Vach W, Kaier K, Ferguson J,
McNally M, etal. Short or Long Antibiotic Regimes
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Practical Lessons Learned
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inManaging Diabetic Foot
Infections
AndrewI.Abadeer, MarkR.Abbruzzese,
andWilliamDavis
14
Introduction
The infectious implications in the diabetic foot cannot be overstated. While it is well known that diabetics have an increased propensity to develop both
systemic and localized infections, the diabetic foot
offers a self-perpetuating cycle for infection that has
been well studied as the most common precipitating
event leading to lower extremity amputation [1–3].
As such, a rm understanding of the pathophysiology and the medical, surgical, and vascular modalities available to the clinician charged with the care
of the infected diabetic foot must inform the allocation of multimodal therapy that is requisite in good
outcomes in this population.
Approximately 85% of lower extremity amputations are preceded by a non-healing foot ulcer
[4]. Complicating this picture, the presence of
infection increases the risk of lower extremity
amputation by 50% [5]. In focusing on the diabetic
foot, current research has demonstrated that the
unique demands in addition to the homeostatic
insult of the disease process inherent to the diabetic
make the diabetic foot uniquely sensitive to clinically devastating infection [6]. While an exhaustive
review of the mechanisms that propagate the sus-
A. I. Abadeer (*) · M. R. Abbruzzese · W. Davis
Medstar Georgetown University Hospital,
Washington, DC, USA
e-mail: Andrew.I.Abadeer@medstar.net;
Mark.Abbruzzese@medstar.net;
William.Davis@gunet.georgetown.edu
ceptibility of the diabetic foot to infection is beyond
the scope of this chapter, a brief review must frame
the clinical management. The disruption of the
homeostatic mechanisms of blood glucose in the
diabetic results in a chronic state of hyperglycemia.
This, in turn, is the cause of upregulation of multiple metabolic pathways which ultimately results in
vascular insufciency. Nerve damage and subsequent paresthesia impair the natural protective sensation of the foot. The immune system is similarly
impaired with studies demonstrating a stunted
immune response to infection with decreased TNFalpha and interleukin- 6 release from macrophages,
demonstrated in animal models [7], impaired polymorphonuclear leukocyte migration, and decreased
efcacy of intracellular killing [5]. Chronic hyperglycemia (beginning as low as serum glucose levels
>150mL/dL [8]) also impairs opsonophagocytosis, the expression of MHC-I expression on
myeloid cells [9, 10], as well as myriad other
mechanisms that continue to be elucidated. As
such, any physical insult to the diabetic foot
becomes immediately compounded by a lack of
sensation, lack of perfusion, and a dysregulated
and inefcient immune system.
Given the “perfect storm” of such disparate
factors that balance the diabetic foot into a precarious homeostasis, it is important that the clinician approach the infected diabetic foot armed
with an informed understanding of the severity of
the patient’s presentation, the utility of investigatory studies and imaging, and the indications,
© Springer Nature Switzerland AG 2023
C. E. Attinger, J. S. Steinberg (eds.), Functional Limb Salvage,
https://doi.org/10.1007/978-3-031-27725-2_14
187
188
A. I. Abadeer et al.
efcacy, and appropriateness of a prescribed antibiotic regimen.
The Initial Presentation
The infected diabetic foot can present along a
broad spectrum ranging from clean ulcers, to a
mild cellulitis, to a life-threatening necrotizing
fasciitis. As such, in an attempt to objectively
grade the severity of the diabetic foot infection,
many classication criteria have been set forth.
The IWGDF has dened a system ranging from a
Classication of 1 (uninfected) to 4 (severe infection) based on a combination of physical examination ndings as well as objective laboratory
data. Conrmation of infection in this grading
system includes physical ndings such as local
swelling/induration, peri-wound erythema, local
pain/tenderness, or purulent discharge. The distinction in the IWGDF classication between
moderate and severe infection is dened as the
presence or absence of two or more of systemic
inammatory response syndrome symptoms
(SIRS, criteria of which include body temperature, heart rate, respiratory rate, and white blood
cell count) [2]. The Infectious Diseases Society
of America (IDSA) also has a similar grading
system based on similar criteria with classications ranging from “Uninfected” to “Severe
Infection” [11, 12]. It is important to note, however, that these classication systems do not then
correlate to a prescribed clinical course of action.
The rst clinical decision point to be made by
the clinician in the ambulatory or emergency setting is a determination of the setting of care
including but not limited to ICU admission, oor
admission, or clinic follow-up. Given the systemic derangements mentioned previously it is
often difcult to efciently characterize a
patient’s wound and the need for admission. In
recognition of this, we recommend a systematic
and organized approach to the initial evaluation
of the infected diabetic foot with emphasis on a
thorough and focused history and physical exam
informed by the judicious use of labs and imaging. The clinician must elicit the relevant course
of the diabetic foot with particular emphasis on
the temporal changes in symptomatology, inciting events, and antecedent trauma. The patient’s
baseline ambulatory status before and after the
current presentation must also be elucidated.
Similarly, glycemic control in the weeks leading
up to presentation should be interrogated
informed by a current Hemoglobin A1C.
Upon clarication of the presenting history,
the physical exam in the infected diabetic foot
must rst begin with a localization of the area of
interest and its character. Often, providers will
nd that patients have kept a photographic
account of their wound which can greatly assist
the clinician in establishing the progression or
regression of a wound. Infection without a corresponding wound should be delimited, circumscribed, and dated, with a marking pen to assess
for attrition. In open wounds, the size of the
wound should be measured and compared to historic values. Specic attention should be sequentially given to the base of the wound and the
surrounding tissues. The base of the wound
should be qualied according to the substrate
(bone vs. soft tissue) as well as the presence or
absence of granulation tissue, brous exudate,
and purulence. Should there be suspicion of bone
at the base of the wound, the probe-to-bone test
should be employed out of concern for osteomyelitis [13]. This test consists of the use of sterile
metal probe to assess if bone comprises the base
of the diabetic ulcer. In the context of cortical
irregularities on X-ray, and laboratory values
suggestive of infection, this triad of ndings is
sufcient to diagnose osteomyelitis without further imaging [2]. The surrounding tissues should
also be inspected closely for uctuance or induration, lymphangitis, or proximal
lymphadenopathy.
Laboratory values such as the white blood cell
count (WBC), C-reactive protein (CRP), and
erythrocyte sedimentation rate (ESR) have an
important role in supplementing and informing
the ndings of the history and physical exam.
The white blood cell is an aggregate marker of
lymphoid and myeloid cells in the bloodstream.
Leukocytosis is generally accepted as suggesting
a pro-inammatory state with differential diagnoses including infection, autoimmune disorders,
14 Practical Lessons Learned inManaging Diabetic Foot Infections
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189
or hematologic neoplastic proliferation. While a
markedly elevated or depressed white blood cell
count may indeed point to underlying infection,
the white blood cell count in diabetics should be
used with caution, particularly when normal.
Often, given the immunologic derangements
described previously, the WBC of a patient with a
diabetic foot infection does not correlate to the
severity of the infection with some studies demonstrating more than half of patients admitted
with diabetic foot infections having a normal
WBC [14]. As such, a normal WBC should not
deter the clinician from escalating care when
confronted with clinical exam ndings concerning for severe infection.
Due to the limitations of the WBC in determining the presence or absence of infection, a
number of adjunctive laboratory measures have
been investigated to supplement the information
gleaned from the WBC including ESR and
CRP. In the author’s experience, these values
have little utility in isolation, but act as an additional datapoint with either an equivocal physical
exam or in the monitoring of treatment efcacy.
In the infected diabetic foot ulcer, a markedly
elevated ESR may also hint at the presence of
osteomyelitis in addition to soft tissue infection.
Importantly, in comparison to ESR, CRP levels
are more responsive to the progression and resolution of infection, making it of higher clinical
utility in tracking treatment efcacy [15, 16].
The decision to hospitalize or manage a
patient as an outpatient depends heavily on each
of these factors. Additional reasons to manage a
patient in an inpatient manner include the need
for advanced diagnostic or interventional procedures, parenteral antibiotics, surgical consultation, the failure of outpatient antibiotics, or the
management of preexisting or exacerbated medical conditions including congestive heart failure,
coronary artery disease, chronic obstructive pulmonary disease, or acute/chronic kidney disease
[2, 17]. Still, while the clinical and laboratory
data that dene the severity of infection must be
a core axis upon which to make the decision for
inpatient admission, this cannot be the only factor informing the care setting. Social support,
wound stability, patient reliability, complexity of
care, and interval of follow-up must also be
thoughtfully considered when evaluating the
infected diabetic foot patient for potential outpatient management. In fact, many a patient’s
wound has deteriorated due to a failure to optimize one or more of these factors when the
wound was clinically stable upon initial
presentation.
Management oftheDiabetic Foot
Infection
The management of diabetic foot infections is
naturally a multidisciplinary endeavor. Due to the
generally complex medical and social comorbidities of this population, a coordinated approach
between infectious disease, medicine, and surgery must be undertaken to optimize patient care.
The mainstay of the clinical approach to the
infected diabetic foot ulcer must be comprised of
surgical debridement and antibiosis. Both the
surgical team and the infectious disease team
should adopt a microbiology-driven approach
based on the available microbiological testing of
their specic institution. Ideally, sterile tissue
cultures would be obtained and sent prior to the
initiation of any antimicrobial therapy (the “sentinel” culture). Still, this is often not possible in
the septic or systemically ill patient in whom
antimicrobial therapy should be initiated immediately. Upon presentation to the operating room,
it has become our practice to obtain a culture
prior to any debridement if it is the rst formal
debridement the patient has undergone. After
appropriate debridement (discussed at length in
Chap. 13) and irrigation, a sterile tissue culture is
again taken and sent for microbiological assessment. The type of culture will depend largely on
the capability of the individual institution though
the sensitivity and specicity of tissue specimens
are generally higher than those of swabs [18–21].
We do not routinely obtain blood cultures on any
patient that is not demonstrating signs of systemic infection.
The duration and type of antimicrobial therapy is made upon the basis of the extent of infection, the involvement of bone, and the type of
190
A. I. Abadeer et al.
pathogen. Osteomyelitis demonstrates a unique
challenge in the treatment of the infected diabetic
foot ulcer. With a positive probe-to-bone test, and
consistent X-ray and clinical ndings, the
treatment of osteomyelitis is based upon surgical
and infectious disease consultation. A sterile
bone biopsy obtained after debridement of an
infected ulcer remains the gold standard for diagnosis of osteomyelitis as these cultures will assist
in the determination of duration and scope of
antibiotic therapy. In consultation with infectious
disease, it is our general practice to treat osteomyelitis with antibiotics at the higher end of the
recommended range and for a longer duration
than patients who have a soft tissue infection
alone [22]. Discussion with the surgical team
after completion of debridement is paramount.
Should the surgical team be condent in a comprehensive osseous debridement back to clinically normal bone supported with a negative
sterile bone culture supporting these ndings, it
is reasonable to then reduce the duration of antibiotic therapy.
Whether by swab, or tissue specimen, a
culture- based approach to antimicrobial therapy
is critical both for antibiotic stewardship, and to
appropriately target and comprehensively treat a
patient’s specic infection. Should empiric coverage be required, this is done based on institutional statistics for most likely pathogens.
Coverage for gram-positive cocci should nearly
always be included in initial empiric coverage,
particularly in MRSA susceptible individuals.
After initial identication of the most likely
pathogen with the sentinel culture, antibiotic
treatment is narrowed according to the institutions antibiogram for local susceptibilities in the
context of a patient’s drug allergies and comorbidities [2]. Still, due to the chronicity of many
diabetic foot ulcers, polymicrobial growth is not
uncommon, and these results should be stratied
according to relative virulence when planning
antibiotic therapy. In infections of the skin and
soft tissues, generally treatment duration need
not exceed 1–2weeks. Wounds with associated
osteomyelitis are generally treated for 6 weeks or
less, with frequent reevaluation for regression or
improvement.
Special populations in the infected diabetic
foot ulcer include those with recent or threatened
skin grafts, free aps, and underlying hardware.
Given the high-risk nature of these circumstances, close consultation with the surgical team
is necessary to determine the scope and duration
of antimicrobial therapy in a case-by-case
manner.
Conclusion
Diabetic foot infections are a devastating, multifaceted, and self-perpetuating consequence of the
diabetic insult to homeostasis. Inadequacy of
diagnosis, treatment, or follow-up can lead to
adverse outcomes including amputation. A
thoughtful and thorough history and physical
examination, buttressed by judicious use of imaging and laboratory values, will empower the clinician to appropriately triage these patients into
an appropriate treatment plan. Close consultation
with surgery as well as an objective, culturebased approach is critical in determining the
duration, scope, and intensity of treatment.
Finally, close surveillance is key to allow for
early detection of failure to improve or worsening infection that may warrant a further workup
or an alternative treatment regimen.
References
1. Ndosi M, Wright-Hughes A, Brown S, Backhouse
M, Lipsky BA, Bhogal M, et al. Prognosis of
the infected diabetic foot ulcer: a 12-month
prospective observational study. Diabet Med.
2018;35(1):78–88.
2. Lipsky BA, Senneville É, Abbas ZG, Aragón-Sánchez
J, Diggle M, Embil JM, etal. Guidelines on the diagnosis and treatment of foot infection in persons with
diabetes (IWGDF 2019 update). Diabetes Metab Res
Rev. 2020;36(Suppl 1):1–24.
3. Tan T-W, Shih C-D, Concha-Moore KC, Diri MM,
Hu B, Marrero D, et al. Disparities in outcomes of
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4. Pecoraro RE, Reiber GE, Burgess EM.Pathways to
diabetic limb amputation basis for prevention: an
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14 Practical Lessons Learned inManaging Diabetic Foot Infections
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5. Hobizal KB, Wukich DK.Diabetic foot infections:
current concept review. Diabet Foot Ankle. 2012:1–8.
6. Boulton AJM. Foot debridement: anatomic knowledge is mandatory. Diabetes Metab Res Rev.
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7. Zykova SN, Jenssen TG, Berdal M, Olsen R,
Myklebust R, Seljelid R. Altered cytokine and
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8. Inzucchi SE. Management of hyperglycemia in the
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9. Mazade MA, Edwards MS. Impairment of type III
group B streptococcus-stimulated superoxide production and opsonophagocytosis by neutrophils in diabetes. Mol Genet Metab. 2001;73(3):259–67.
10. Price CL, Hassi HOSA, English NR, Blakemore
AIF, Stagg AJ, Knight SC.Methylglyoxal modulates
immune responses: relevance to diabetes. J Cell Mol
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11. Ince P, Abbas ZG, Lutale JK, Basit A, Ali SM,
Chohan F, et al. Use of the SINBAD classication
system and score in comparing outcome of foot ulcer
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12. Zhan LX, Branco BC, Armstrong DG, Mills JL Sr.
The society for vascular surgery lower extremity
threatened limb classication system based on wound,
ischemia, and foot infection (WIfI) correlates with
risk of major amputation and time to wound healing. J
Vasc Surg. 2015;61(4):939–44.
13. Grayson ML, Gibbons GW, Balogh K, Levin E,
Karchmer AW. Probing to bone in infected pedal
ulcers: a clinical sign of underlying osteomyelitis in
diabetic patients. JAMA. 1995;273(9):721–3.
14. Armstrong DG, Perales TA, Murff RT, Edelson GW,
Welchon JG. Value of white blood cell count with
differential in the acute diabetic foot infection. J Am
Podiatr Med Assoc. 1996;86(5):224–7.
15. Xu J, Cheng F, Li Y, Zhang J, Feng S, Wang
P.Erythrocyte sedimentation rate combined with the
probe-to-bone test for fast and early diagnosis of diabetic foot osteomyelitis. Int J Low Extrem Wounds.
2020;20:1534734620923278.
16. Crisologo PA, Davis KE, Ahn J, Farrar D, Van Asten
S, La Fontaine J, etal. The infected diabetic foot: can
serum biomarkers predict osteomyelitis after hospital
discharge for diabetic foot infections? Wound Repair
Regen. 2020;28(5):617–22.
17. Wukich DK, Hobizal KB, Brooks MM.Severity of
diabetic foot infection and rate of limb salvage. Foot
Ankle Int. 2013;34(3):351–8.
18. Nelson A, Wright-Hughes A, Backhouse MR, Lipsky
BA, Nixon J, Bhogal MS, etal. CODIFI (concordance
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infected diabetic foot ulcers in England. BMJ Open.
2018;8(1):e019437.
19. Huang Y, Cao Y, Zou M, Luo X, Jiang Y, Xue Y,
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S, Dalton J, etal. A series of systematic reviews to
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22. Spellberg B, Lipsky BA.Systemic antibiotic therapy
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Managing Soft Tissue Infection
intheDiabetic Foot: Cultures,
Drugs, andSource Control
EricSenneville andRominaDeldar
15
Soft Tissue Infection
oftheDiabeticFoot
Diabetic foot infection (DFI) is classically
dened by the multiplication of microorganisms
and invasion of the tissues surrounding a wound
located under the malleoli. Although the microorganisms that invade the skin and soft tissues
(SSTs) around and/or beneath a wound ulcer cannot be seen on physical examination, they are
consistently present on the ulcer surface [1]. The
consequences of these postulates are (a) infection
of a diabetic foot ulcer cannot be established by
means of microbiological assessment and (b) the
best way to diagnose infection is to assess the
SSTs around the ulcer for the presence of clinical
signs of infection [2].
DFIs usually are due to a neuro/vasculopathic
ulcer but other causes include a simple puncture,
a wound in the interdigital space, or from the nail
plate. The colonization of the wound by pathogenic microorganisms such as Staphylococcus
E. Senneville
Infectious Diseases Department, Gustave Dron
Hospital, Tourcoing, France
e-mail: esenneville@ch-tourcoing.fr
R. Deldar (*)
Department of Plastic and Reconstructive Surgery,
MedStar Georgetown University Hospital,
Washington, DC, USA
e-mail: Romina.Deldar@medstar.net
aureus or beta-hemolytic streptococci (e.g.,
Streptococcus agalactiae) may lead to an acute
infection. Non-healing ulcers seen in patients living with diabetes mellitus (DM) are mainly a
consequence of peripheral neuropathy which permits the patient to keep walking on the wound
because of the loss of pain sensation and/or
peripheral arterial disease (PAD) both of which
can delay ulcer healing and, as result, favor the
occurrence of a DFI.Although not fully understood, the immunological dysfunction associated
with diabetes increases the risk of infection [3].
Pathogenic bacteria and commensals (e.g., S. epi-
dermidis, Corynebacterium spp.) coexist in nonhealing foot ulcers and interact with each other as
they do in other wounds [1]. Recent advances in
knowledge about the microbiota of DFUs have
promoted the concept of pathogenicity of bacteria in DFUs as bacterial communities rather than
independent specic bacteria [4]. The bacterial
population present in a DFU is therefore now
considered a functional unit that organizes itself
as functionally pathogroups secondary to the
interactions between commensals and virulent
bacteria. For instance, the commensal bacterium
Helcococcus kunzii can reduce the virulence
expression in S. aureus [5].
© Springer Nature Switzerland AG 2023
C. E. Attinger, J. S. Steinberg (eds.), Functional Limb Salvage,
https://doi.org/10.1007/978-3-031-27725-2_15
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E. Senneville and R. Deldar
Microbiology oftheDiabetic Foot
Numerous distinct microorganisms including
bacteria and fungi can be identied in DFUs [6].
Studies have principally addressed bacteria that
are consistently identied in DFUs. S. aureus is
by far the most prevalent microorganism identied in temperate regions, while Gram-negative
bacilli especially Pseudomonas spp. are most
commonly identied in warm climate countries
[7, 8].
The duration of a DFU is a major reason it
can become infected. S. aureus strains present in
non- healing DFUs are likely to harbor antibiotic
resistance and encode staphylococcal enterotoxin genes resulting in nonspecic stimulation
of a wide population of T cells responsible for
persistent inammation which delays the healing process [5]. The expression of bacterial virulence inuences the evolution of a DFU towards
infection; this has been observed in S. aureus in
which several virulent genes have been signicantly associated with the evolution to infection
[6]. Enterobacterales (e.g., Proteus mirabilis,
Escherichia coli, Klebsiella sp., or Enterobacter
sp.) and strict anaerobes (e.g., Finegoldia sp.,
Bacteroides sp.) are usually encountered during
chronic wound infections [9–12]. Fungal agents,
in particular Candida sp., are not uncommon
[13]. More than half of infected DFUs are polymicrobial [9–12]. Recent data suggest that the
expression of virulence can be attenuated by
antibiotics and also stress conditions in the ulcer
environment (e.g., oxygen pressure, low temperature, elevated glucose concentration, nutrient
limitation) [14]. These elements lead to the
emergence of quasi-dormant subpopulations of
bacteria, including small-colony variants likely
to exhibit antibiotic resistance and biolm formation that are inaccessible to most antibiotic
agents [15]. Polymicrobial biolms, in which
bacterial strains organized in pathogroups can
escape the host immune responses, are involved
in 60–80% of non-healing DFUs compared to
6% in acute DFUs [16].
Diagnosis ofSoft Tissue Infections
oftheDiabetic Foot
The diagnosis of a DFU infection is a major step
that allows for the implementation of all therapeutic measures, but also importantly can help
reduce the unjustied use of broad-spectrum
antibiotics since no clinical studies have demonstrated any benet of systemic antibiotic therapy
on the evolution of an uninfected diabetic foot
wound [17]. According to the denition of DFI
proposed by the International Working Group on
the Diabetic Foot (IWGDF), the clinical elements
suggestive of a DFU infection include at least
two of the following: local swelling or induration, erythema >0.5cm around the wound limits,
sensibility, or local pain (rare), increased local
heat, and the presence of pus located under the
malleoli [2]. The IWGDF proposes to grade the
severity of the infection according to the surface
and depth extension (moderate infection), presence of systemic signs (severe infection), and
involvement of underlying osteoarticular structures (see Chap. 17) [2].
Microbiological Assessment ofSoft
Tissue Infections
oftheDiabeticFoot
Once a clinical suspicion of DFI is established, a
microbiologic assessment is recommended to
best target antimicrobial therapy [18]. Overall,
tissue samples (curettage-biopsy, true-cut biopsy,
needle aspiration, especially in the case of a subcutaneous abscess) have a sensitivity and specicity higher than those of simple swabs which
are not recommended as they do not allow for the
distinction between pathogens and colonizers
[19]. One technique using swabs (Levine’s technique) has been validated for microbiological
assessment of a DFU.It consists of rotating the
wound swab over a 1-cm2 area of the wound [20].
The quality of the sample is very important since
the detection of live bacteria in a tissue sample
15 Managing Soft Tissue Infection intheDiabetic Foot: Cultures, Drugs, andSource Control
195
taken appropriately to avoid contamination is a
strong argument for the pathogenicity of the
microorganism(s) identied. However, it may not
always be practical or feasible to obtain the most
sophisticated samples, thus it is preferable to at
least obtain a sample even if it is not of optimal
quality than to not do it at all. In cases when
obtaining a culture is not feasible, any microbiological information, such as Gram stain [21], can
help tailor antibiotic treatment, especially in
cases of poor evolution after rst-line antibiotic
treatment. The concordance between Gram stain
and culture results established in diabetic patients
with SST infection of the foot is likely to augment the pathogenic role of the identied bacteria and may help providers choose the most
appropriate antibiotic regimens [2].
New molecular techniques can now identify
most of the microorganisms present in a
DFU.These techniques cannot, however, differentiate living from dead microorganisms, and
they do not provide data about the antibiotic sensitivities of identied bacteria. At best, they can
determine the presence of certain resistance
genes. Moreover, there are no criteria to ascertain
that isolated bacteria are responsible for an infection diagnosed clinically. As a result, although
these new techniques are essential to understand
the pathophysiology of wound infection and the
relations between microbes and wound healing,
they do not yet have a place in the daily care of
patients with DFIs [2]. One exception is the
detection by direct polymerase chain reaction
(PCR) of methicillin-resistant S. aureus (MRSA)
nasal carriage, which has been signicantly associated with MRSA DFI and can aid in the choice
of antibiotics in patients with DFIs and screening
for MRSA colonization in DFU patients [22, 23].
Biomarkers ofInfection
Serum biomarkers of inammation, such as
C-Reactive Protein (CRP) and procalcitonin,
may be useful in situations where the clinical
diagnosis of DFI is uncertain [24]. They can also
be used to assess the evolution of infection as it
increases rapidly at the beginning of an infection
and then decreases when the infection improves.
The level of leukocytes and/or neutrophils is not
helpful to diagnose infection as they can be normal in more than half of cases [25]. However,
leukocyte counts may be useful since it is part of
the criteria for dening a severe infection (grade
4in the IWGDF classication; see Chap. 15).
Management oftheDiabetic Foot
Infection
Surgical Part ofthe Treatment
ofInfection
The surgical management of DFIs and osteomyelitis is detailed in Chap. 14. It is important to
consider surgical intervention as a major, even
indispensable in some cases, mode of infection
source control. Surgical debridement is a radical
weapon against infection to remove any necrotic
material and drain purulent collections, which are
not accessible to the activity of most antibiotics.
Neglecting this essential therapeutic step can
lead to the spread of infection and treatment failure. In addition, exposing high bacterial loads to
inappropriate antibiotic concentrations because
of the necrotic nature of infected tissue will likely
favor the emergence of multidrug-resistant
bacteria.
Antimicrobial Therapy
General Aspects
Antimicrobial therapy of DFIs is almost always
empiric since it is recommended to start treatment as soon as the infection is diagnosed as the
outcome of the infection is not predictable in this
setting [2]. Knowledge of which microorganisms
are likely to be involved in DFIs can aid in choosing empirical antimicrobial treatment. Therefore,
to tailor empiric antibiotic therapy, it is important
to consider epidemiological data on bacterial
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E. Senneville and R. Deldar
ecology, if available, and to involve microbiologists/infectious disease consultants in complex
cases [26]. The goal of empiric initial antibiotic
therapy is to cover the likely pathogens and to
avoid the use of unnecessary broad-spectrum
antibiotics, as antimicrobial resistance is more
likely to emerge with broad versus narrow
antibiotics.
The choice of an antibiotic regimen to treat a
DFI should be based on the likely
microorganism(s) and its(their) antibiotic susceptibilities. Patients with infected non-necrotic
acute wounds who have not recently been treated
with antibiotics are likely to be infected with S.
aureus and/or beta-hemolytic streptococci [2]. In
warm climate countries, the higher prevalence of
Gram-negative bacilli may justify the use of
broader-spectrum antibiotics. Strict anaerobes
involved in DFIs are generally susceptible to
most antibiotics, except Bacteroides species.
Other important criteria include infection severity, existing data on the efcacy of the agent in
treating DFIs, its tolerance prole, including the
risk of drug-drug interactions, mode of administration, and cost.
Parenteral antibiotic therapy is indicated initially in some moderate and all severe DFIs. A
switch to oral form should be considered once the
patient is clinically improving, as long as he/she
has no contraindications to oral therapy and an
oral regimen is available. In other cases, patients
with DFIs can be treated with oral agents providing the oral bioavailability is correct (i.e., oral
oxacillin should be avoided, but cephalexin is a
good option).
The duration of antibiotic therapy for DFI is a
matter of debate. The recommendations have
evolved in the past few decades to include duration of 1–2 weeks for SST DFIs. Prolonging
treatment for up to 3–4 weeks is proposed by
IWGDF in cases of extensive infection that is
improving slower than expected or if the patient
has severe peripheral artery disease [2]. It is
important to specify a treatment end date when
prescribing an antibiotic regimen to avoid unnecessary prolonged treatments and to discourage
prolongation of treatment until the wound has
healed [17].
Antibiotics Useful fortheTreatment
ofSST DFIs
As only one randomized study has established
the superiority of ertapenem over tigecycline
[27], the current recommendations for empiric
antibiotic therapy for DFIs are mainly based on
expert opinions [2].
Intravenous vancomycin can be used empirically to cover Gram-positive cocci (i.e.,
methicillin- resistant staphylococci) in conjunction with antibiotics against Gram-negative
bacilli (GNB) and strict anaerobes, such as
piperacillin- tazobactam or carbapenems, in moderate to severe cases due to the narrow-spectrum
of vancomycin. The IDSA recommends a dose of
15–20 mg/kg every 8–12 h for S. aureus to
achieve a minimal inhibitory concentration
(MIC) ≤1mg/L [28]. The use of vancomycin in
patients who are age 65years or older with renal
disease and/or take other nephrotoxic medications exposes those patients to the risk of renal
toxicity. Daptomycin, a cyclic lipopeptide, has
the same antibacterial spectrum as vancomycin,
with a higher and faster bactericidal effect and
almost no renal toxicity.
The combination of the group A penicillin
agent, amoxicillin, with the beta-lactamase inhibitor (BLI) clavulanic acid confers a broadspectrum oral antibiotic against beta-hemolytic
streptococci, methicillin-susceptible staphylococci, some GBN (e.g., Proteus mirabilis and
some strains of E. coli), and almost all strict
anaerobes. This combination is recommended for
the treatment of mild to moderate SST DFIs
especially chronic ulcers in which polymicrobial
communities may be involved, DFIs, and localized cellulitis. The drug does not provide any
coverage against bone infections.
Among the anti-Gram-negative antibiotics,
both ceftazidime and cefepime have the advantage
to cover Pseudomonas aeruginosa, although the
direct pathogenicity of this bacterium has been
questioned, as it was for Enterococcus faecalis, in
the setting of SST DFIs. Cefepime exhibits some
activity against AmpC (depressed chromosomic
cephalosporinases)-producing GNB, particularly
Enterobacter sp. Both ceftazidime and cefepime
can result in serious adverse nervous system
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