A Current Overview of Chronic Wounds

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ORIGINAL RESEARCH

A Current Overview of Chronic Wounds


Presenting to a Plastic Surgery Unit in Central
Chronic Wound Care Management and Research downloaded from https://www.dovepress.com/ on 13-Sep-2022

India
This article was published in the following Dove Press journal:
Chronic Wound Care Management and Research

Manal M Khan Purpose: To analyze the demographic, clinical, and microbiological profile of patients
Ved Prakash Rao Cheruvu presenting to our unit with chronic wounds of various etiologies with an intent to give a
Deepak Krishna current overview of chronic wounds.
Reena Minz Patients and Methods: We performed a prospective observational study of patients
For personal use only.

presenting with chronic wounds from October 2018 to September 2019. The study was
Michael Laitonjam
conducted at the Department of Burns and Plastic Surgery of a tertiary care institute in a non-
Rishabh Joshi
metropolitan city in Central India. A total of 103 patients were included in the study. Data
Department of Burns and Plastic Surgery, collected from the patients included demographic details, history, clinical features, and
All India Institute of Medical Sciences,
Bhopal, Madhya Pradesh, India relevant laboratory reports. Wound swabs obtained by Levine’s technique were sent for
culture and sensitivity studies. Treatment was instituted according to the clinical picture and
modified if necessary. Progress was monitored until the wound healed, either by conservative
management or by surgical intervention. Patients were followed up for six months thereafter.
Results: Most of the patients presented with lower limb wounds (n=81, 78.64%). Swab
specimens from 103 wounds were cultured. Among the isolates, gram-negative organisms
were more common than gram-positive organisms. Staphylococcus aureus was the most
common species isolated, followed by Pseudomonas aeruginosa. The frequency of infections
caused by other gram-negative organisms like Klebsiella pneumoniae, Escherichia coli, and
Proteus mirabilis was on the rise. There were significant differences in the patterns of
antimicrobial resistance in our patients. Sharp debridements were required in almost all
cases for wound preparation. Most of the patients (n=74, 71.84%) underwent surgical
intervention for achieving wound closure. Split-thickness skin grafting (STSG) was the
most common surgical intervention performed (n=45, 43.68% patients), followed by local
and distant flaps.
Conclusion: Our study gives a current overview of the causes, clinical presentation,
prevalent microbial flora, and their antibiotic susceptibilities prevalent in chronic wounds
presenting to our unit. Treatments administered are discussed with emphasis on the different
reconstructions performed.
Keywords: anti-bacterial agents, biofilms, drug resistance, multiple bacterial, Pseudomonas
aeruginosa, Staphylococcus aureus, wound healing

Correspondence: Ved Prakash Rao


Cheruvu
Department of Burns and Plastic Surgery, Introduction
All India Institute of Medical Sciences, 1st Chronic wounds are often painful, debilitating and profoundly impair the quality of
Floor, Hospital Building, Saket Nagar,
Bhopal, Madhya Pradesh 462020, India life of the affected individuals.1 They impose an enormous economic burden on the
Tel +91 8872209777 patients and healthcare systems around the world. A study estimated that there were
Email vedprakash.
plasticsurg@aiimsbhopal.edu.in 2.2 million patients in the United Kingdom with a wound, equating to 4.5% of the

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http://doi.org/10.2147/CWCMR.S267428
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Khan et al Dovepress

adult population. This led to 3.4 million hospital outpatient onto the wound bed forming new colonies that can lead to
visits annually and a cost of £5.3 billion for managing local infection or weakening of the collagen matrix.24,25
these wounds and the associated comorbidities.2 Over the years, increasing resistance to commonly used
According to some estimates, chronic wounds of the antibiotics has been seen in chronic wounds.3 The increas­
lower extremity affected 2.4–4.5 million people in the ing prevalence of multidrug-resistant organisms has com­
United States.3,4 Chronic wound infections caused plicated the choice of selecting an appropriate antibiotic
approximately 85% of all non-traumatic lower-limb ampu­ for treating chronic wound infections. An understanding of
tations and 7–8% of fatalities in spinal cord injury the challenges in the management of chronic wounds and
victims.1,5,6 effectively addressing them will lead to a better outcome
Wound healing involves a cascade of complex and in terms of improved quality of life of the patients,
dynamic processes that can be affected by various factors reduced morbidity, mortality, and decreased healthcare
such as elderly age, underlying diseases (venous incompe­ costs. Figure 1 shows the various types of chronic wounds
tence, diabetes, and arterial insufficiency), obesity, medica­ that are usually treated at our unit.
tions, poor nutrition, and infection resulting in a chronic The objective of this study was to analyze the demo­
wound.7 Several factors affect the wound’s ability to progress graphic, clinical, and microbiological profiles of patients
from the inflammatory phase to the proliferation phase.8 These presenting to our unit with chronic wounds of various
include the underlying pathology, presence of non-viable tis­ etiologies. We intend to present a current overview of
sue, and abnormal immune cell activity, which results in an chronic wounds with regards to causes, clinical features,
excessive release of MMPs (matrix metalloproteinases). This organisms isolated, antibiotic sensitivity profiles, treat­
process perpetuates the cycle of wound chronicity and extra­ ments administered, and their outcomes.
cellular matrix destruction.9 Chronic wounds are also charac­
terized by senescent cells which have decreased proliferative Patients and Methods
and secretory capacities and decreased responsiveness to the
Study Design
wound healing signals.10–13
We performed a prospective observational study of
All chronic wounds naturally contain microorganisms.
patients presenting to us with chronic wounds over a
Microbial involvement of a wound can be described in the
period of one year, from October 2018 to September
terms of the wound infection continuum: contamination,
2019. The study was conducted at the Department of
colonization, local infection, spreading infection, and sys­
Burns and Plastic Surgery of a tertiary care institute in a
temic infection.14 Clinically, a chronic wound infection can
non-metropolitan city in Central India.
present with impaired healing, unhealthy granulation tissue,
putrid odor, increased exudate, erythema >1–2 cm, warmth
around the wound, and necrotic tissue.15 The majority of
Inclusion Criteria
Patients who presented to us with chronic wounds
chronic wounds have been reported to consist of a predomi­
(≥3weeks duration) of any etiology and were willing to
nantly polymicrobial flora composed of aerobes and anae­
participate in the study.
robes, although, delayed wound healing with or without
clinical signs of infection was more commonly associated
with aerobic or facultative pathogens. Staphylococcus aur­ Exclusion Criteria
eus, Pseudomonas aeruginosa, and beta-hemolytic None.
Streptococci were reported as the most common pathogens
causing chronic wound infections in some earlier studies.16 Method
Evidence suggests that biofilms are present in over Permission for conducting the study was obtained from the
90% of chronic wounds.17 During the inflammatory Institutional Human Ethics Committee (no. IHEC-LOP/
response to wound infection, leukocytes attach to the 2018/IM0194). The study protocol conformed to the ethi­
biofilm and release enzymes that propagate the inflamma­ cal guidelines of the 1975 Declaration of Helsinki. Written
tory response and affects the healing processes, leading to informed consent was obtained from all the participants
the persistence of chronic wound.18–23 Biofilms exhibit the before their inclusion in the study. Data collected from the
ability to mutate and alter their sensitivity to antibacterial patients included demographic details, history, clinical
agents. Planktonic bacteria are released from the biofilm features, and relevant laboratory reports.

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Figure 1 Spectrum of chronic wounds presenting to our unit. (A) Long-standing post-traumatic chronic wound over leg region. (B) Chronic wound on the leg following
cellulitis. (C) Trochanteric pressure sore. (D) Venous ulcer in the gaiter area. (E) Diabetic foot ulcer. (F) Chronic wound following a thermal burn.

After assessment and photographic documentation, a treatment was performed with sharp/mechanical debride­
sample was taken from the wound for culture and sensi­ ments followed by dressings with different agents. The
tivity studies. When a patient presented with multiple progress was monitored until the wound healed, either by
wounds, the largest wound was selected for sampling and conservative management or by surgical intervention.
analysis. An area near the center of the wound free of STSG (Split-thickness skin grafts), local and distant flaps
necrotic tissue and debris was pre-cleaned with non-bac­ were the various surgical interventions performed. Patients
teriostatic saline. Then, the end of a culture swab was were followed-up for six months after the wound healed.
rotated over a 1 cm2 area for 5 seconds with sufficient
pressure to extract fluid from within the wound tissue Statistical Analysis
(Levine’s technique).26 All specimens were appropriately All the patient and wound data were entered in a spread­
labeled and dispatched together with patient information sheet created in Microsoft Excel™ software 2013 version
sheets for aerobic culture and antibiotic sensitivity studies. (©Microsoft Corporation, Redmond, Washington, United
All the specimens were analyzed by the same microbiolo­ States). Data analysis was carried out using Epi Info soft­
gical laboratory. Standard antibiotic susceptibility testing ware version 7.2 (Epi Info™, Centers for Disease Control
was performed for the most commonly used antibiotics. and Prevention, Atlanta, Georgia). Nominal variables were
Empirical treatment was instituted if needed, according statistically described with frequencies and percentages.
to the clinical picture and severity at presentation. Once Continuous variables were described with means and stan­
culture and sensitivity reports were available, treatment dard deviations. Ordinal variables were also presented in
was instituted or modified, as necessary. Local wound the form of frequencies and percentages.

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Results Table 1 Demographic and Clinical Characteristics of the Patients


A total of 103 patients were included in the study (Table 1). Characteristics No. of patients n (%)
There were 79 (76.69%) males and 24 (23.3%) females, with
1. Sex
a male to female ratio of 3.29:1. The age of the patients Males 79 (76.69)
ranged from 3 to 86 years with a mean age and standard Females 24 (23.3)
deviation of 40.96 years and 16.307, respectively. Trauma Male:Female ratio 3.29:1
and infection were the most frequent causes of chronic 2. Age in years: mean (SD) 40.96 (16.307); age range: 3-
wounds in the study. Majority of the patients presented with 86 years
lower limb wounds (n=81, 78.64%). The size of the index
3. Duration of wound in weeks
wound ranged from 1.57 cm2 to 675 cm2 at presentation. category
Swab specimens from 103 wounds were cultured and ≤12 weeks 60 (58.25)
99 pathogenic organisms belonging to 17 different species >12 to 24 weeks 14 (13.59)
were isolated (Table 2). Seventy-five wounds (72.81%) >24 to 52 weeks 14 (13.59)
had growth of a single organism from the wound. >52 to 104 weeks 12 (11.65)
>104 to 156 weeks 3 (2.91)
Among the isolates, gram-negative organisms were more
common compared to gram-positive organisms (62 and 37 4. Etiology
isolates, respectively). Staphylococcus aureus was the Trauma 29 (28.15)
Infection 25 (24.27)
most common species isolated with 30 isolates (30 of 99,
Burns 14 (13.59)
30.30%). There were 20 (20.20%) isolates of a) Scald 7 (6.79)
Pseudomonas aeruginosa. b) Thermal 3 (2.91)
Antibiotic sensitivity profiles of the isolates to commonly c) Electrical 3 (2.91)
used antibiotics were analyzed. Among the MSSA (methicil­ d) Chemical 1 (0.97)
lin-sensitive Staphylococcus aureus) strains, 77.77% (14 of Venous incompetence 11 (10.67)
Diabetic foot 9 (8.73)
18) isolates were either sensitive or had intermediate sensitiv­
Pressure sore 7 (6.79)
ity to Co-trimoxazole; 88.88% isolates were either sensitive or Unstable scar 5 (4.85)
had intermediate sensitivity to Tetracycline and Clindamycin. Hansen’s 2 (1.94)
Around 61.11% MSSA isolates showed resistance to Marjolin’s ulcer 1 (0.97)
Levofloxacin, 77.77% isolates showed resistance to 5. Number of wounds at
Ciprofloxacin, and 55.55% isolates showed resistance to presentation
Erythromycin. One 89 (86.4)
In MRSA (methicillin-resistant Staphylococcus aureus) Two 11 (10.67)
isolates, 91.66% (11 of 12) isolates were sensitive to Three or more 3 (2.91)

Clindamycin, 66.66% isolates were either sensitive or had 6. Site


intermediate sensitivity to Erythromycin, and all isolates were Head and Neck 5 (4.85)
sensitive to Vancomycin. Around 91.66% MRSA isolates Upper Limb 9 (8.73)
Trunk 8 (7.76)
were resistant to Penicillin, Ciprofloxacin, and
Lower Limb 81 (78.64)
Levofloxacin; 58.33% isolates were resistant to Co-
trimoxazole. 7. Wound size in cm2 categories
1-10 30 (29.12)
Among Pseudomonas aeruginosa strains isolated, 95%
10.1-20 13 (12.62)
(19 of 20) were either sensitive or had intermediate sensi­
20.1-50 17 (16.5)
tivity to Piperacillin+Tazobactam, 85% isolates were 50.1-100 21 (20.38)
either sensitive or had intermediate sensitivity to 100.1-200 17 (16.5)
Gentamycin, 80% isolates were sensitive to 200.1-500 3 (2.91)
Ciprofloxacin, and 60% isolates were sensitive to >500 2 (1.94)

Cefepime. Thirty percent isolates of Pseudomonas Abbreviation: SD, standard deviation.

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Table 2 Organisms Isolated Table 3 Treatments and Complications


Characteristics Result Treatment Modality No. of Patients n
(%)
1. No. of isolates per wound No. of patients n (%)
One 75 (72.81) 1. Conservative Management 29 (28.15)
Two 11 (10.67)
2. Surgical intervention 74 (71.84)
Three or more 8 (7.76)
a) STSG 45 (43.68)
No Growth 9 (8.73)
b) Random pattern local flaps 5 (4.85)
2. Gram staining of the isolates No. of isolates n (%) Transposition flap 1
Total no. of isolates 99 Rotation flap 1
Gram-positive organisms 37 (37.37) Limberg flap 1
Gram-negative organisms 62 (62.62) V-Y advancement flap 1
Bilateral V-Y advancement flap 1
3. Organism No. of isolates n
c) Perforator based local flaps 18 (17.47)
Staphylococcus aureus 30
Sural artery flap 13
a) MSSA 18
Posterior tibial artery perforator based 2
b) MRSA 12
fascio-cutaneous peninsular flap
Pseudomonas aeruginosa 20
Pedicled ALT flap 1
Klebsiella pneumoniae 12
Superior gluteal artery perforator based 1
Escherichia coli 10
pedicled islanded flap
Proteus mirabilis 8
FDMA flap 1
Enterobacter species 4
d) Muscle flaps 2 (1.94)
Acinetobacter baumanii 3
Hemi-soleus flap 1
Streptococcus pyogenes 2
Tensor fascia lata rotation advancement flap 1
Enterococcus species 2
e) Free flaps 2 (1.94)
Proteus vulgaris, Proteus hauseri 1 each
Free ALT flap 2
Providencia stuartii, Citrobacter species, f) Cross-leg flap 1 (0.97)
Methicillin-resistant coagulase negative g) Above knee amputation 1 (0.97)
Staphylococcus, Klebsiella oxytoca,
Complications
Methicillin-resistant Staphylococcus
Early No. of patients n
haemolyticus, Staphylococcus lugdunensis
1. Small areas of graft loss treated 11
Abbreviations: MSSA, Methicillin-sensitive Staphylococcus aureus; MRSA, Methicillin- conservatively
resistant Staphylococcus aureus.
2. Partial graft loss requiring re-grafting 6
3. Venous congestion in Sural artery flap 2
4. Superficial necrosis in distal part of FDMA 1
aeruginosa were resistant to Ticarcillin+Clavulanate, flap
Tobramycin, and Meropenem. 5. Total flap loss in free ALT flap 1
Table 3 presents the treatments used in the study subjects
Long term
and complications. Most of the patients (n=74, 71.84%) Wounding in the skin grafts 9
needed surgical intervention for achieving wound closure.
Abbreviations: STSG, split-thickness skin grafting; ALT flap, anterolateral thigh
Among these, split-thickness skin grafting (STSG) was the flap; FDMA flap, first dorsal metatarsal artery flap.

most common surgical intervention performed, accounting


for 43.68% (n=45) patients. Other procedures that were leg region underwent an above-knee amputation. Three
performed include random pattern local flaps, perforator- other patients who were kept on conservative management
based local flaps, muscle flaps, free flaps, and a cross-leg on an outpatient basis and had initial improvement in their
flap. Figures 2 and 3 show the pre-operative and post-opera­ wounds were lost to follow up.
tive pictures of the cases in which a surgical intervention
(skin graft or flap) was performed. Twenty-nine (28.15%) Discussion
patients were treated conservatively. Trauma and infection accounted for causing the majority
Wound closure was achieved in most of the patients, (52.42%) of the chronic wounds in our study population.
except for four. One patient who presented with a long- This finding can be correlated with the male preponderance
standing previously undiagnosed Marjolin’s ulcer of the (76.69%), as males are more susceptible to occupational and

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Figure 2 (A) Patient presenting with a post-thermal burn chronic wound over the posterior aspect of the leg. (B) Four weeks following split-thickness skin grafting with a
well-settled graft.

Figure 3 (A) Patient presenting with a long-standing post-traumatic chronic wound over the dorsum of the foot. (B) Two months following excision of the wound and
reconstruction with islanded Sural artery flap.

accidental trauma. Burns, venous disease, diabetic foot, and measures in the management of chronic wound infections
pressure injuries were some of the other important causes. that are unresponsive to standard treatment. Many chronic
Gupta et al conducted a community-based cross-sectional wounds are indiscriminately treated with antibiotics because
study on the epidemiology of wounds and reported that of the belief that high wound bioburden contributes to delayed
untreated trauma, diabetes, and leprosy were the common healing.26 In the present study, we have used wound swabs
causes of chronic wounds in their study population.27 This obtained by Levine’s technique for cultures. These swabs
profile is different from that of western literature in which the improve the ability to verify which of the chronic wounds
majority of the chronic wounds are caused by venous disease really have high bioburden, thus decreasing the number of
followed by arterial disease. patients receiving unnecessary antibiotic treatment. The
In our study, most of the chronic wounds were located Levine method samples both the surface biofilm and from
in the lower limbs (78.64%). The vulnerability of the beneath the surface,24,26 and the culture results are comparable
lower limbs for wounding has been consistently reported to those obtained by tissue biopsy.26,32,33 An international
in many of the earlier studies.1,27–31 Most of the patients consensus update on wound infection published in 2016 also
presented with a single wound. But 14 (13.58%) patients recommended Levine’s technique as it was more effective
had two or more wounds at presentation. than Z-swab technique for microbial cultures.14
Identification of the causative organisms by microbial Previous studies have shown that chronic wounds
cultures and specific anti-microbial therapy are important mostly have a polymicrobial flora.24 In our study, the

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majority (n=75, 72.81%) of the wounds had only one frequency of infections caused by other gram-negative
organism isolated from the wound in aerobic cultures. organisms such as Klebsiella pneumoniae, Escherichia
There were only 10.67% wounds with 2 species isolated coli, and Proteus mirabilis are increasing.
from the wound and 7.76% wounds with 3 or more species In our study, apart from the anti-microbial therapy to
isolated from the wound. No pathogenic organism was treat wound infections, wound bed preparation was done
isolated in 8.73% wounds. Overall, there were more with a combination of sharp/mechanical debridements fol­
gram-negative organisms isolated than gram-positive lowed by dressings with different agents (Table S1, supple
organisms. We believe that these findings should be care­ mentary data). Nanocrystalline silver gel was the most
fully considered when selecting empirical antibiotic ther­ common dressing agent used in the study patients.
apy in patients presenting with severe infections. Madhusudhan performed a prospective randomized con­
Empirical antibiotic therapy should also include coverage trolled trial in pseudomonal wound infections and con­
for MSSA or MRSA in patients at risk of these infections. cluded that 1% acetic acid is a simple, safe and effective
Angel et al reported that Staphylococcus aureus and topical antiseptic that can be used in the elimination of P.
Pseudomonas aeruginosa are the most commonly isolated aeruginosa from chronic-infected wounds.37
pathogens in chronic wounds.24 Our study revealed similar Sharp/mechanical debridements were performed in
findings. Staphylococcal species comprised 33.3% of all iso­ almost all of our study patients. Attempts were made to
lates recovered; 90.9% of these isolates comprised perform debridement at every dressing until the wound
Staphylococcus aureus. Pseudomonas aeruginosa was the was grossly free from slough. Necrotic tissue in the form
second most common species isolated comprising 20.20% of slough or eschar is very commonly found in chronic
isolates. wounds.38 It not only affects wound healing but also
The emergence of community-acquired MRSA has heightens the risk of infection.39 Therefore, debridements
been previously studied.34,35 In our study, cultures of spe­ are required to get rid of the non-viable tissue and disrupt
cimens from 12 (11.65%) patients had grown MRSA. We the biofilms. Appropriate debridement helps accelerate the
found that 91.66% MRSA isolates were susceptible to wound healing process, by removing the barrier of non-
Clindamycin and 100% isolates were susceptible to viable tissue.40 It also helps to break down the defenses of
Vancomycin. Vancomycin should be considered as the the microbes, exposing them, and permitting more effec­
drug of choice for treating MRSA infections caused by tive action of topical antimicrobials.41 The importance of
multi-drug resistant strains. Clindamycin can be consid­ surgical debridement in wound bed preparation and its role
ered as an alternative in less severe cases. We have also in disrupting biofilms has been highlighted in the recent
found that 91.66% of MRSA strains were resistant to international consensus studies.42,43 In our study, 28.15%
Ciprofloxacin and Levofloxacin. Some earlier studies also of patients underwent conservative management alone,
reported 80% quinolone resistance in MRSA.36 Hence, which consisted of debridements, dressings, and anti-
quinolones should not be considered as an option for microbials, when needed.
empirical therapy, in cases where MRSA is suspected. Around 71.84% patients underwent surgical interven­
Even in cases of MSSA, we do not recommend therapy tion, in addition to conservative management. The cover­
with Quinolones considering the degree of resistance age provided included split-thickness skin grafts, local and
among the isolates (77.77% isolates resistant to distant flaps. Langer et al performed a prospective study
Ciprofloxacin and 61.11% resistant to Levofloxacin). on the adjunctive role of NPWT (Negative-pressure
Valencia et al reported in their study that more than wound therapy) in the healing of chronic wounds.44 A
half (56%) of the Pseudomonas aeruginosa isolates from significant observation from this study is that, in their
leg ulcers were resistant to quinolones.30 In contrast, we study group of 60 patients, they identified that coverage
found out that in our study subjects, Pseudomonas aeru­ in the form of a flap was required at presentation in
ginosa isolates were largely sensitive to quinolones (80% 63.33% of patients with chronic wounds. Hence, we can
isolates were sensitive to Ciprofloxacin and 75% isolates infer that where available, early referral to reconstructive
were sensitive to Levofloxacin). Therefore, we propose services may shorten the course and improve the outcome
that quinolones can be considered as an option for the in chronic wounds. Further, in this study, after the institu­
empirical treatment of suspected Pseudomonas aeruginosa tion of NPWT, 60% of the patients had wound healing by
infections of chronic wounds. We have also found that the secondary intention, and 40% of patients required split-

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thickness skin grafts.44 In our study, STSG was performed and Plastic Surgery, AIIMS Bhopal. Dr Reena Minz,
in 43.68% of the patients. MBBS, MS, is a Senior Resident at the Department of
Our study had some limitations. We did not employ Burns and Plastic Surgery, AIIMS Bhopal. Dr Michael
methods to isolate anaerobic organisms and fungi because Laitonjam, MBBS, MS, is a Senior Resident at the
of some logistical constraints. Also, the small sample size Department of Burns and Plastic Surgery, AIIMS
in our study may not be enough to draw general conclu­ Bhopal. Dr Rishabh Joshi, MBBS, MS, is a Senior
sions applicable to all types of chronic wounds in different Resident at the Department of Burns and Plastic Surgery,
settings. Further studies with larger sample sizes are AIIMS, Bhopal.
necessary.
Funding
Conclusion We have not received any financial or material support for
Chronic wounds impose an enormous burden on the conducting this study.
patients and healthcare systems around the world.
Knowledge regarding the causative factors, prevalent Disclosure
organisms in chronic wound infections, antibiotic suscept­ The authors report no conflicts of interest, financial or
ibility patterns of the isolates, and treatment options is otherwise, in relation to this work.
extremely useful to all the people involved in patient
care, infection control, healthcare administration, and References
planning. Our study gives a current overview of the
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