antibiotics
Article
Medical-Grade Honey as an Alternative Treatment for
Antibiotics in Non-Healing Wounds—A Prospective Case Series
Adéla Holubová 1,2, *, Lucie Chlupáčová 2 , Lada Cetlová 3 , Niels A. J. Cremers 4






Citation: Holubová, A.; Chlupáčová,
L.; Cetlová, L.; Cremers, N.A.J.;
Pokorná, A. Medical-Grade Honey as
an Alternative Treatment for
Antibiotics in Non-Healing
Wounds—A Prospective Case Series.
Antibiotics 2021, 10, 918. https://
doi.org/10.3390/antibiotics10080918
Academic Editor: Piotr Szweda
Received: 25 June 2021
Accepted: 25 July 2021
Published: 28 July 2021
Publisher’s Note: MDPI stays neutral
with regard to jurisdictional claims in
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iations.
Copyright: © 2021 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and
conditions of the Creative Commons
Attribution (CC BY) license (https://
creativecommons.org/licenses/by/
4.0/).
Antibiotics 2021, 10, 918. https://doi.org/10.3390/antibiotics10080918
and Andrea Pokorná 3,5
1 Faculty of Health and Social Sciences, University of Bohemia, 370 11 České Budějovice, Czech Republic
2 DiaPodi Care spol. s r.o., 392 01 Soběslav, Czech Republic; diapodicare@seznam.cz
3 Department of Health Sciences, College of Polytechnics Jihlava, 586 01 Jihlava, Czech Republic;
lada.cetlova@vspj.cz (L.C.); apokorna@med.muni.cz (A.P.)
4 Triticum Exploitatie BV, 6222 NK Maastricht, The Netherlands; niels@mesitran.com
5 Department of Nursing and Midwifery, Faculty of Medicine, Masaryk University,
625 00 Brno, Czech Republic
* Correspondence: adela.holubova@diapodicare.cz; Tel.: +420-774-672-220
Abstract: Non-healing wounds are usually colonised by various types of bacteria. An alternative
to antibiotic treatment in patients with infected wounds with local signs of inflammation may be
medical-grade honey (MGH), which favourably affects the healing process with its antimicrobial,
antioxidant, anti-inflammatory, and immunomodulatory properties. The objective of this study was
to evaluate the effect of MGH therapy on the healing process of non-healing wounds of various
aetiologies and different wound colonisations. Prospective, observation–intervention case studies
(n = 9) of patients with wounds of various aetiologies (venous leg ulcers, diabetic foot ulcers, surgical
wound dehiscence) are presented. All wounds were treated with MGH and the healing trajectory
was rigorously and objectively monitored. In all cases, pain, odour, and exudation were quickly
resolved, which led to an improvement in the quality of life of patients. Despite the proven bacterial
microflora in wounds, antibiotic treatment was not necessary. The effects of MGH alleviated the
signs of local infection until their complete elimination. In eight out of nine cases, the non-healing
wound was completely healed. MGH has antimicrobial, anti-inflammatory, and antioxidant effects in
wounds of various aetiologies and forms an effective alternative for the use of antibiotics for treating
locally infected wounds.
Keywords: medical grade honey; antibiotic replacement; infections; wounds; objective wound
assessment
1. Introduction
The Wound Healing Society has defined four categories of non-healing ulcers based
on their aetiology: pressure ulcers, diabetic ulcers, and ulcers due to venous insufficiency
or arterial insufficiency [1]. A non-healing wound, also called a hard to heal or chronic
wound, is damage to the skin that heals unusually slow. Depending on the definition, a
non-healing wound is usually present for at least 4 weeks [2]. Non-healing wounds have a
major impact on the patient’s quality of life [3,4]. Therefore, the main goal in the treatment
of non-healing wounds is not only their healing but also the alleviation of unpleasant
wound symptoms, such as pain and malodour [5]. An objective assessment of non-healing
wounds, including the overall condition of the patient, is very important to develop a
realistic treatment plan and to determine cost-effectivity [6–9].
The wound healing process is complex and dynamic [10,11]. Non-healing wounds are
often critically colonized by various types of microorganisms. Local signs of inflammation
in the wound include redness, oedema, increase in local temperature, tissue damage, and
pain. In difficult-to-heal or non-healing wounds, they also include prolonged healing, the
presence of abnormal granulation tissue, increase in wound size, and increased amount
https://www.mdpi.com/journal/antibiotics
Antibiotics 2021, 10, 918 2 of 14

of exudate [12]. Antibiotic treatment based only on the presence of bacteria is not a good
practice and is potentially dangerous with respect to the formation of polyresistant micro-
bial strains, and ultimately leads to increased therapy costs and resource wastage [13,14].
The amount and behaviour of bacteria in wounds varies from contamination to invasive
infection. Biofilm is often present, which is a bacterial colony surrounded by an extracel-
lular matrix consisting of polysaccharides forming a shield to antimicrobial agents and
increasing resistance [15]. One of the options to reduce the bioburden of the wound bed
is sharp debridement. Debridement refers to a process in which avital tissue, coatings,
microbial load (including biofilms), and tissue debris are removed from a wound [16–18].
Sharp debridement accelerates wound cleansing and shortens the total time required for
tissue repair, but has low selectivity and often damages vital tissues [19,20]. Therefore, it is
appropriate to use less invasive but similarly effective autolytic debridement techniques.
One of them is the use of medical-grade honey (MGH).
Honey has been used to treat wounds and local infections for more than 5000 years [21].
MGH is carefully selected and gamma-sterilized in order to ensure safe use for wound
care [22,23]. MGH has a positive effect on the healing process with its antimicrobial,
antioxidant, anti-inflammatory, and immunomodulatory properties. It also stimulates
the production of hydrogen peroxide at a concentration that is not toxic to damaged
tissues [24,25]. It also supports the activity of the immune system, debridement, and
stimulates regenerative processes in the wound [26]. MGH decreases wound healing time
and is cost-effective [27]. The aim of our study was to assess the effect of MGH on the
healing of non-healing wounds. In this prospective case series, nine patients with infected
non-healing wounds were treated with MGH in the absence of antibiotics. Our hypothesis
was that MGH could replace the use of antibiotics in locally infected wounds and promote
debridement, wound healing, and patients’ quality of life.

2. Results
2.1. Case 1: Dehisced Surgical Wound
A 57-year-old female patient presented with a dehisced surgical wound at her left
breast following a breast-conserving operation as a result of being diagnosed with breast
cancer (Figure 1a). Relevant comorbidities included ovarian cancer and having diabetes
mellitus (DM) type 2, which could subsequently affect the healing. Previous treatments
with sterile bioceramic dressings for three months were ineffective. The wound dimensions
upon presentation were 6 cm in length, 1.5 cm in width, and ranging from 0.5 cm to 2 cm in
depth (deeper towards axilla). The wound consisted mainly (roughly 95%) of granulation
tissue and 5% slough. Low levels of exudate (thin, water-like) were produced. Local signs
of infection included delayed healing, pain, and redness. The pain was scored on a visual
analogue (VAS)-scale by the patient for pain level during the daytime and during wound
care treatment. Pain level was 5 during the daytime and 8 during treatment. L-Mesitran®
Soft gel (MGH) was applied inside the lesion and followed by L-Mesitran® Tulle (MGH) to
ensure contact to the wound. Mepilex foam (foam dressing) was applied as a secondary
dressing. Wound dressings were performed by the patient at home at 72 h intervals for
the first two weeks. Pain and redness disappeared after 14 days of treatment. Due to the
positive evolution of the healing, the dressing changes interval were extended to every
four days. The wound was completely healed after 35 days of MGH treatment without
complications (Figure 1b).
 Antibiotics 2021, 10, 918 3 of 14
Antibiotics 2021, 10, 918 3 of 14
Antibiotics 2021, 10, 918 3 of 14

(a) (b)
(a) (b)
Figure 1. Case 1: Dehiscence of the surgical wound on the left breast. (a) Local finding at initial examination, day 0 (start
Figure 1. Case
Figure
of MGH 1:1:Dehiscence
1. Case Dehiscence of
treatment). thewound
of the
(b) Complete surgical
surgical wound
wound
healing
on on
thethe
left left
on follow-up breast.
breast. (a) at
(a) Local
examination Local
day finding
finding atexamination,
at initial
35. initial examination, day
day 0 (start of 0 (start
of MGH
MGH treatment). (b)Complete
treatment). (b) Complete wound
wound healing
healing on follow-up
on follow-up examination
examination at day 35.
at day 35.
2.2. Case
2.2. Case 2:
2: Venous
Venous Leg
Leg Ulcer
Ulcer
2.2. Case 2: Venous Leg Ulcer
A 43-year-old male patient presented with a venous leg ulcer at his right lower leg
A 43-year-old male patient presented with a venous leg ulcer at his right lower leg
A 43-year-old
(Figure
(Figure Relevantmale
2a). Relevant
2a). patient included
comorbidities
comorbidities presented
includedchronic withvenous
chronic avenous
venous leg ulcer(CHVI),
insufficiency
insufficiency at his right
(CHVI), diabe-
diabetes lower leg
(Figure
mellitus 2a).
tes mellitus (DM), Relevant
(DM), obesity
obesity comorbidities
(BMI(BMI30), and included
30), repeated
and repeated chronic
venous venous venous
lower lower
ulcers. insufficiency
ulcers. Previous
Previous (CHVI),
treat- diabe-
treatments
ments
tes with
mellitus iodinated
(DM), povidone
obesity (BMIsolution
30), for
and two months
repeated
with iodinated povidone solution for two months were ineffective. The wound dimen- were
venous ineffective.
lower The
ulcers. wound
Previous di- treat-
mensions
ments upon presentation
with presentation
sions upon iodinated povidone were
were 6 cm 6 cm
solution in length,
in length, for 5two 5 cm
cm months in width,
in width, were and 1 cm in
and ineffective. depth.
1 cm in depth. The TheThe
wound di-
wound consisted
mensions
wound consisted of
of5%
upon presentation5%ofofgranulation
were 6tissue
granulation cm inand
tissue 95%
length,
and 95%slough.
5 cm inLow
slough. levelslevels
width,
Low of exudate
and 1 of in(thin,
cmexudate depth. The
water-like) were produced. Local signs of of infection included pain, erythema, local
wound
(thin, consistedwere
water-like) of 5% of granulation
produced. Local tissue
signs and 95% included
infection slough. Low pain,levels of exudate
erythema, local (thin,
warmth, exudate,
warmth, exudate,delayed
delayedhealing, healing,andand malodour.microbiological
malodour. A microbiological swab was per-
water-like) were produced. Local signs of A infection included swabpain,
was performed,
erythema, local
formed,
in whichin which Enterococcus
Enterococcus faecalis (resistant
faecalis (resistant to Trimethoprim
to Trimethoprim + sulphonamide,
+ sulphonamide, neomycin, neomy-clin-
warmth,
cin, exudate,
clindamycin, delayed and
gentamicin; healing,
sensitiveandto malodour.
ampicillin, A microbiological
nitrofurantoin, swabbac-
norfloxacin, was per-
damycin, gentamicin; and sensitive to ampicillin, nitrofurantoin, norfloxacin, bacitracin,
formed, in which
itracin, ciprofloxacin,
ciprofloxacin, and Enterococcus faecalis
and chloramphenicol)
chloramphenicol) and(resistant
Escherichia tocoli
Trimethoprim
and Escherichia without + sulphonamide,
coli resistance
without resistance
were detectedwereneomy-
cin,
(sensitive to ampicillin, aminopenicillin, cefuroxime, trimethoprim + sulphonamide, cef- bac-
clindamycin,
detected (sensitive gentamicin;
to ampicillin, and sensitive
aminopenicillin, to ampicillin,
cefuroxime, nitrofurantoin,
trimethoprim + norfloxacin,
sulphona-
itracin,
podoxime, ciprofloxacin,
mide, cefpodoxime,neomycin,neomycin, and chloramphenicol)
gentamicin, gentamicin,
ciprofloxacin, and
ciprofloxacin,Escherichia coli without
and chloramphenicol).
and chloramphenicol). Pain levelresistance
wasPain 8 were
detected
level was
during the (sensitive
8daytime
during and to ampicillin,
the 9daytime andaminopenicillin,
during treatment.9 during treatment.
L-Mesitran cefuroxime,
L-Mesitran
® Ointment trimethoprim
® Ointment (MGH)
(MGH) was applied + sulphona-
to
waswound
mide,
the applied
cefpodoxime,to the 2b)
(Figure wound (Figure gentamicin,
neomycin,
and followed 2b)
by and followed
L-Mesitran by L-Mesitran
ciprofloxacin,
® Tulle (Figure and Tulle
2c)® to (Figure
chloramphenicol).
ensure contact2c) toto Pain
level was 8 during the daytime and 9 during treatment. L-Mesitran Ointmenta(MGH)
ensure
the wound contactbed. to the
Suprasorb wound P bed.
foam Suprasorb
(foam dressing)P foam was (foam
applied dressing)
as a was
secondary®applied as
dressing.
secondary
Wound
was applied dressing.
dressings were
to the Wound
wound dressings
performed by the
(Figure were
2b) performed
patient
and at homeby
followed the
atby hpatient
48L-Mesitran at home
intervals for theatfirst
® Tulle 48 htwo
(Figurein- 2c) to
tervals After
weeks. for the20firstdays, two theweeks.
woundAfter 20 days,upon
dimensions the wound
presentation dimensionswere 4 upon
cm in presentation
length, 4 cm
ensure contact to the wound bed. Suprasorb P foam (foam dressing) was applied as a
were
in 4 cmand
width, in length,
0.5 cm4in cmdepth
in width, and2d).
(Figure 0.5 cm The inwound
depth (Figure
consisted 2d).ofThe
20% wound consisted
of granulation
secondary dressing. Wound dressings wereand performed by theinfection
patient disappeared.
at home at 48 h in-
of 20% 30%
tissue, of granulation
epithelializing,tissue,and30%50%epithelializing,
slough, and 50% slough,
malodour and and malodour and in-
tervals
fection
Pain for
levels the first two
disappeared.
gradually Pain weeks.
levelsand
decreased After
after20
gradually days,
days ofthe
20decreased wound
and
treatment,afterthe dimensions
20 pain
dayslevel upon
of treatment,
was presentation
the
2 (VAS).
were 4 cm in length, 4 cm in width, and 0.5 cm in depth
pain level was 2 (VAS). Due to the positive development of healing, the dressing changes
Due to the positive development of healing, the dressing (Figure
changes were2d). The
extended wound
to every consisted
of
were extended to every three days. The wound was completely healed after 67 days ofand in-
20%
three of
days. granulation
The wound tissue,
was 30%
completely epithelializing,
healed after and
67 days 50% of slough,
MGH and
treatment malodour
without
fection disappeared.
MGH treatment
complications without
(Figure Pain
2e). levels gradually
complications (Figuredecreased
2e). and after 20 days of treatment, the
pain level was 2 (VAS). Due to the positive development of healing, the dressing changes
were extended to every three days. The wound was completely healed after 67 days of
MGH treatment without complications (Figure 2e).

(a) (b) (c)

Figure 2. Cont.

(a) (b) (c)

otics 2021, 10, 918 4 of 14

Antibiotics 2021, 10, 918 4 of 14

Antibiotics 2021, 10, 918 4 of 14

(d) (e)
Figure 2. Case 2: Venous leg ulcer on the right lower leg. (a) Local finding at initial examination, day 0 (start of MGH
treatment). (b) Example of L-Mesitran® Ointment application. (c) Example of L-Mesitran® Tulle application. (d) Follow-
up examination at day 20. (e) Complete wound healing on follow-up examination at day 67.
(d) (e)
Figure
Figure 2.
2. Case
Case 2:2: Venous
2.3. Case 3:
Venous leg ulcer
ulcer on
legVenous the
onLeg right
right lower
the Ulcer lower leg.
leg. (a)
(a) Local
Local finding
finding at
at initial
initial examination,
examination, dayday 00 (start
(start of
of MGH
MGH
treatment).
treatment). (b) Example of
(b) Example of L-Mesitran
L-Mesitran®® Ointment
Ointmentapplication.
application.(c)(c)Example
ExampleofofL-Mesitran
L-Mesitran Tulle
® ®Tulle application.
application. (d)(d) Follow-
Follow-up
up examination
examination at day
A(e)
at day 72-year-old
20. 20. (e) Complete
Complete
male
wound
wound
patient
healing
healing
presented
on on follow-up
follow-up
with a venous
examination
examination
leg ulcer on his right lower leg
at day
at day 67. 67.
(Figure 3a). Relevant comorbidities included CHVI, DM, hypertension (HT), and a medi-
cal history2.3.
of Case
2.3. Case3:3:Venous
thrombosis Venous ofLeg
the
Leg Ulcer
right lower leg without acute symptomatology. Previous
Ulcer
treatments with Aiodinated
A 72-year-oldpovidone
72-year-old male
male patient solution
patient presented
presented for six with
withweeks wereleg
aa venous
venous ineffective.
leg ulcer
ulcer onon hisUpon
his rightpresen-
right lower
lower leg leg
tation, the(Figure
wound
(Figure dimensions
3a).
3a). Relevant were 14 cmincluded
comorbidities
Relevant comorbidities in length,
included CHVI,
CHVI, 4 cm DM,
DM, inhypertension
width, and(HT),
hypertension 1(HT),
cmand in adepth.
and amedical
medi-
The wound cal history
consisted
history of of
thrombosis
30% of
of thrombosis of the
rightright
of granulation
the lower lower
tissue leg
and
leg without without
70%
acute acute
slough. symptomatology.
Medium levels
symptomatology. Previous
Previousof ex-treat-
treatments
udate (thin,ments withwith
water-like) iodinated
were
iodinated povidone
produced.
povidone solution
Local
solution signs
for forweeks
six sixinfection
of weeks
werewere ineffective.
included
ineffective. pain,
Upon Upon presen-
delayed
presentation,
tation,
healing, and the wound
themalodour.
wound dimensions
dimensions
A swab were
was14 were
cm in14
performed cminin4which
length, length,
cm 4 cm and
in width, in width,
Enterococcus 1 cm inand 1 cmThe
depth.
faecalis in wound
(resistant depth.
to
The woundofconsisted
consisted of 30% of granulation
30% of granulation tissue and 70% tissue and 70%
slough. slough.levels
Medium Medium levels of
of exudate ex-
(thin,
trimethoprim + sulphonamide, neomycin, clindamycin, and gentamicin; and sensitive to
udate (thin, were
water-like) water-like)
produced. wereLocal
produced.
signs of Local signs included
infection of infection included
pain, delayedpain, delayed
healing, and
ampicillin,malodour.
nitrofurantoin, bacitracin, ciprofloxacin, chloramphenicol) and Escherichia coli
healing, andAmalodour. A swab was
swab was performed inperformed Enterococcus
in whichfaecalis
which Enterococcus faecalis
(resistant (resistant to
to trimethoprim
without resistance
trimethoprim
+ sulphonamide,were detected
neomycin,(and
+ sulphonamide, sensitive
neomycin,
clindamycin, and togentamicin;
ampicillin,
clindamycin, and
andaminopenicillin,
gentamicin;
sensitive to and cefurox-
sensitive
ampicillin, to
nitro-
ime, trimethoprim
ampicillin, + sulphonamide,
nitrofurantoin,
furantoin, bacitracin, cefpodoxime,
bacitracin,
ciprofloxacin, gentamicin,
ciprofloxacin, chloramphenicol)
chloramphenicol) ciprofloxacin,
and Escherichia coliand withoutand chlo-
Escherichia
resistance coli
ramphenicol).
werePain
without level(and
resistance
detected waswere6 during to the
detected
sensitive daytime
(and
ampicillin, sensitive and to 9ampicillin,
during cefuroxime,
aminopenicillin, treatment. L-Mesitran
aminopenicillin, cefurox-
trimethoprim ® +

Ointment ime,
was trimethoprim
applied tocefpodoxime,
sulphonamide, the+ wound and followed
sulphonamide,
gentamicin, cefpodoxime, by L-Mesitran
ciprofloxacin,gentamicin, ® Tulle. Resposorb
ciprofloxacin,
and chloramphenicol). PainSu-
and ® chlo-
level
® Ointment was applied
per (super absorbent dressing) was applied as a secondary dressing. Wound dressings ®
ramphenicol).
was 6 during Pain
the level
daytime wasand 6 during
9 during the daytime
treatment. and 9 during
L-Mesitran treatment. L-Mesitran
® Tulle. Resposorb® Super
Ointment
were performed bywas
to the wound applied
the patient to home
at
and followed the by
wound
at 48and followed
h intervals
L-Mesitran bythe
for L-Mesitran
first two® Tulle.
weeks. Resposorb
Painabsorbent
(super ® Su-
levels
graduallyper (super absorbent
and afterdressing) was applied asthe a secondary
pain was dressing.
toleratedWound at pain dressings
dressing) was applied as a secondary dressing. Wound dressings were performed by the
decreased 14 days of treatment, level 1
(daytime)were
and performed by the patient at home at pain). 48 h intervals for the first twodevelopment
weeks. Pain levels
patient at home at 48 h intervals for the first two weeks. Pain levels gradually decreased
2 (during treatment–procedural Due to the positive of
gradually
and after 14 decreased and after 14
days of treatment, thedays
painofwas treatment,
tolerated the
at pain
pain was
leveltolerated
1 (daytime) at pain
and level
2 (dur- 1
healing, theingdressing changes were extended
Due to to theevery three days. After 42 days,theonly L-
(daytime) and 2 (during
treatment–procedural treatment–procedural
pain). pain).
positive Due to
development the positive development
of healing, dressing of
Mesitran® changes
Tulle was wereapplied
extendedto the wound.
to every threeSuprasorb
days. to P foam
After wasonly
42 days, applied as a secondary
L-Mesitran ® Tulle was
healing, the dressing changes were extended every three days. After 42 days, only L-
dressing. Mesitran
The wound
applied to thewas
® Tulle wascompletely
wound. Suprasorb
applied to thehealed
foam after
P wound. was 79 days
applied
Suprasorb as aofsecondary
P foam MGH treatment
dressing.
was applied without
as aThe wound
secondary
complications
was (Figure
completely 3b).
healed after 79 days of MGH treatment
dressing. The wound was completely healed after 79 days of MGH treatment without without complications (Figure 3b).
complications (Figure 3b).

(a) (a) (b) (b)

Figure 3. Case
Figure
Figure3: 3.
Venous
3. Case 3:leg
Case 3: ulcerleg
Venous
Venous onulcer
leg the on
ulcer right
onthe lower
theright
right leg.
lower
lower (a)leg.
leg. Local
(a)(a) finding
Local
Local atatinitial
finding
finding examination,
at initial
initial examination,
examination, day
day 0 (startday 0 (start
0of(start
MGH of MGH
of MGH treatment).
treatment). (b) Complete
(b) Complete
treatment). wound
(b) Complete woundwound
healing healing
healing on follow-up
ononfollow-up
follow-up examination
examination
examination at day
atatday
day 79.79.
79.
Antibiotics 2021, 10, 918 5 of 14

Antibiotics 2021, 10, 918 5 of 14

2.4. Case 4: Venous Leg Ulcer

A 75-year-old female patient presented with a venous leg ulcer on her left lower leg
2.4. Case 4: Venous Leg Ulcer
(Figure 4a). Relevant comorbidities included CHVI, DM, HT, and the patient underwent
A 75-year-old
varices surgery on thefemale patientleg
left lower presented with
in the past witha venous
no actual legsymptomatology.
ulcer on her left lower leg
Previous
(Figure 4a). Relevant comorbidities included CHVI, DM, HT, and the patient underwent
treatments with antiseptic dressing with silver nanoparticles for two months were inef-
varices surgery on the left lower leg in the past with no actual symptomatology. Previ-
fective. Upon presentation, the wound dimensions were 1.5 cm in length, 1.5 cm in width,
ous treatments with antiseptic dressing with silver nanoparticles for two months were
and 0.8 cm in depth (top wound) and 3 cm in length, 2 cm in width, and 0.8 cm in depth
ineffective. Upon presentation, the wound dimensions were 1.5 cm in length, 1.5 cm in
(lower wound), both in craniocaudal direction. The wound bed consisted of 30% of gran-
width, and 0.8 cm in depth (top wound) and 3 cm in length, 2 cm in width, and 0.8 cm in
ulation tissue and 70% slough. Medium levels of exudate (thin, water-like) were pro-
depth (lower wound), both in craniocaudal direction. The wound bed consisted of 30%
duced. Local signs of infection included pain and delayed healing. A wound swab con-
of granulation tissue and 70% slough. Medium levels of exudate (thin, water-like) were
firmed the presence of Staphylococcus aureus resistant to clindamycin and sensitive to tri-
produced. Local signs of infection included pain and delayed healing. A wound swab
methoprim + sulphonamide, norfloxacin, neomycin, bacitracin, chloramphenicol, and
confirmed the presence of Staphylococcus aureus resistant to clindamycin and sensitive to
gentamicin. Pain level was 5 during the daytime and 7 during treatment (procedural
trimethoprim + sulphonamide, norfloxacin, neomycin, bacitracin, chloramphenicol, and
pain). L-Mesitran® Ointment was applied to the wound and followed by L-Mesitran®
gentamicin. Pain level was 5 during the daytime and 7 during treatment (procedural
Tulle.
pain). Resposorb
L-Mesitran®Super
® (foamwas
Ointment dressing)
appliedwas applied
to the wound as aandsecondary
followeddressing. Wound
by L-Mesitran ®
dressings were performed
® by the patient at home at 48 h intervals
Tulle. Resposorb Super (foam dressing) was applied as a secondary dressing. Wound for the first two weeks.
After 51 days,
dressings werethe wound dimensions
performed by the patient were 6 cm in
at home length,
at 48 6 cm in
h intervals forwidth, and
the first 0.5weeks.
two cm in
depth (Figure 4b). The wound bed consisted of 70% of granulation
After 51 days, the wound dimensions were 6 cm in length, 6 cm in width, and 0.5 cm tissue and 30% epithe-
lialization tissue. Pain
in depth (Figure 4b). levels gradually
The wound beddecreased
consisted and afterof14granulation
of 70% days of treatment, the pain
tissue and 30%
level during the daytime was 1 and during treatment it was rated
epithelialization tissue. Pain levels gradually decreased and after 14 days of treatment, at level 2. After the
proposed topical treatment, the wound bed was cleansed, the granulation
the pain level during the daytime was 1 and during treatment it was rated at level 2. and epitheliali-
zationthe
After phases took place,
proposed topicalbut the wound
treatment, thearea
wound increased
bed was despite getting
cleansed, the more superficial.
granulation and
There was also a reduction in wound exudate and pain, and local signs
epithelialization phases took place, but the wound area increased despite getting more of infection disap-
peared. Due There
superficial. to these aspects,
was also athe dressingin
reduction was changed
wound to L-Mesitran
exudate and pain, ® Net (MGH) (Figure
and local signs of
4c) and PermaFoam
infection disappeared. ® classic (foam dressing) was used as a secondary dressing. Due to the
Due to these aspects, the dressing was changed to L-Mesitran®
positive
Net (MGH) development
(Figure 4c)ofandhealing, the dressing
PermaFoam changes
® classic (foamwere extended
dressing) to every
was used as athree days.
secondary
The wound
dressing. Duewastocompletely
the positivehealed after 62 of
development days of MGH
healing, thetreatment withoutwere
dressing changes complications
extended
(Figure
to every4d).
three days. The wound was completely healed after 62 days of MGH treatment
without complications (Figure 4d).

(a) (b) (c) (d)

Figure 4.
Figure 4. Case
Case 4:
4: Venous
Venous leg ulcer on
leg ulcer on the
the left
left lower
lower leg.
leg. (a)
(a) Local finding at
Local finding at initial
initial examination,
examination, day
day 00 (start
(start of
of MGH
MGH
treatment). (b)
treatment). (b) Follow-up
Follow-up examination
examination atat day
day 51.
51. (c)
(c) Example
Example of L-Mesitran®® N
of L-Mesitran et application.
Net application. (d)
(d) Complete
Complete wound
wound healing
healing
on follow-up
on follow-up examination
examination at
at day
day 62.
62.

2.5.
2.5. Case
Case 5:
5: Diabetic
Diabetic Foot
Foot Ulcer
Ulcer
A
A 59-year-old
59-year-oldmale
malepatient
patientpresented
presented with
witha diabetic footfoot
a diabetic ulcer at his
ulcer at right foot (Fig-
his right foot
ure 5a). 5a).
(Figure Relevant comorbidities
Relevant comorbiditiesincluded repeated
included diabetic
repeated gangrene,
diabetic repeated
gangrene, amputa-
repeated am-
tion of toes
putation ofon theon
toes right
thefoot,
rightdiabetic neuropathy,
foot, diabetic DM, HT,DM,
neuropathy, and HT,
obesity
and(BMI 32). (BMI
obesity Previous
32).
treatments with iodinated povidone solution for six weeks were ineffective. Upon presen-
Previous treatments with iodinated povidone solution for six weeks were ineffective. Upon
tation, the wound
presentation, dimensions
the wound were 8were
dimensions cm in length,
8 cm 3 cm in
in length, width,
3 cm and 5and
in width, cm 5incmdepth. The
in depth.
wound
The wound consisted of 80%
consisted of 80%of granulation
of granulation tissue
tissueand
and20%
20%slough.
slough.High
Highlevels
levels of exudate
of exudate
(thin, water-like)were
(thin, water-like) wereproduced.
produced.LocalLocal signs
signs of infection
of infection included
included low low
levellevel of neuro-
of neuropathic
pathic pain, exudate,
pain, exudate, delayeddelayed
healing,healing, and malodour.
and malodour. There wasThere was maceration,
maceration, hyperkera-
hyperkeratosis and
tosis and callus in the peri-wound skin. A wound swab confirmed the presence of Proteus
callus in the peri-wound skin. A wound swab confirmed the presence of Proteus mirabilis
(resistant to ampicillin, aminopenicillin, cefuroxime, trimethoprim + sulphonamide, cef-
podoxime, gentamicin, ciprofloxacin, chloramphenicol, and cefotaxime; and sensitive to
Antibiotics 2021, 10, 918 6 of 14

Antibiotics 2021, 10, 918 mirabilis (resistant to ampicillin, aminopenicillin, cefuroxime, trimethoprim + sulphona- 6 of 14

mide, cefpodoxime, gentamicin, ciprofloxacin, chloramphenicol, and cefotaxime; and sen-

sitive to neomycin, amikacin, ceftazidime, ertapenem, meropenem), Staphylococcus aureus
(resistant to clindamycin,
neomycin, gentamicin;ertapenem,
amikacin, ceftazidime, and sensitive to cefoxitin,
meropenem), trimethoprim
Staphylococcus + sulphon-
aureus (resistant
amide, norfloxacin, neomycin,
to clindamycin, gentamicin;bacitracin, chloramphenicol,
and sensitive fusidic acid, +and
to cefoxitin, trimethoprim mupirocin)
sulphonamide,
and Acinetobacter baumanii (resistant
norfloxacin, neomycin, to ampicillin,
bacitracin, aminopenicillin,
chloramphenicol, fusidic acid,cefuroxime, cefpodox-
and mupirocin) and
ime, Acinetobacter
chloramphenicol,baumaniicefotaxime; and
(resistant to sensitiveaminopenicillin,
ampicillin, to trimethoprim + sulphonamide,
cefuroxime, neo-
cefpodoxime,
mycin, gentamicin, ciprofloxacin,
chloramphenicol, cefotaxime; andamikacin, ceftazidime).
sensitive Pain level
to trimethoprim was 1 duringneomycin,
+ sulphonamide, the day-
time gentamicin,
as well as during treatment
ciprofloxacin, (diabetic
amikacin, neuropathy).
ceftazidime). L-Mesitran
Pain level ® Ointment
was 1 during was ap-
the daytime as
®
pliedwell
to the wound,treatment
as during followed(diabetic
by L-Mesitran ® TulleL-Mesitran
neuropathy). (Figure 5b) Ointment
and Resposorb ® Super
was applied toas a
the
wound, followed by L-Mesitran ® Tulle (Figure 5b) and Resposorb® Super as a secondary
secondary dressing. Wound dressings were performed by the patient at home at 48 h in-
dressing.
tervals due to Wound
bacterialdressings
findingswere
andperformed
heavy wound by the patient atfor
exudation homefirstatfollow-up
48 h intervals due to
examina-
bacterial findings and heavy wound exudation for first follow-up examination. On day 25,
tion. On day 25, the wound dimensions were 5 cm in length, 1.5 cm in width, and 1 cm in
the wound dimensions were 5 cm in length, 1.5 cm in width, and 1 cm in depth (Figure 5c).
depth (Figure 5c). The wound consisted of 90% of granulation tissue and 10% slough. Pain
The wound consisted of 90% of granulation tissue and 10% slough. Pain and odour levels
and odour levels gradually decreased over time and were completely absent on day 25.
gradually decreased over time and were completely absent on day 25. After the proposed
Aftertopical
the proposed
treatment, topical treatment,
the wound the wound
area was reducedareaandwas reducedbed
the wound andwasthecleaned.
wound Due bed
was to
cleaned. Due to the occurrence of maceration, likely due to non-compliance
the occurrence of maceration, likely due to non-compliance to the treatment, topical to the
treatment, topical treatment was slightly adjusted. The application
® of L-Mesitran
treatment was slightly adjusted. The application of L-Mesitran Ointment was omitted and ® Oint-

mentthewas omitted
patient wasand the patient
advised was treatment
to continue advised toatcontinue
home at treatment
48 h intervalsat home
due toatmoderate
48 h in-
tervals due to
wound moderate wound exudation.
exudation.

(a) (b) (c)

Figure 5. Case
Figure 5: Diabetic
5. Case foot foot
5: Diabetic ulcerulcer
on the
on right foot.foot.
the right (a) Local finding
(a) Local at initial
finding examination,
at initial day
examination, 0
day
(start0of(start
MGH of treatment). (b) Example
MGH treatment). of L-Mesitran
(b) Example ® Tulle
of L-Mesitran application. (c) Improved wound heal-
® Tulle application. (c) Improved wound

ing on follow-up
healing examination
on follow-up at day 25.
examination at day 25.

2.6. Case 6: Venous Leg Ulcer

2.6. Case 6: Venous Leg Ulcer
A 54-year-old male patient presented with a venous leg ulcer at his right lower
A 54-year-old male patient presented with a venous leg ulcer at his right lower leg
leg (Figure 6a). Relevant comorbidities included CHVI, HT, DM, hyperlipidaemia, and
(Figure 6a). Relevant comorbidities included CHVI, HT, DM, hyperlipidaemia, and hype-
hyperuricemia. Previous treatments with iodinated povidone solution for seven weeks
ruricemia. Previous treatments
were ineffective. with iodinated
Upon presentation, povidone
the wound solution
dimensions werefor6 seven
cm in weeks
length, were
6 cm
ineffective. Upon presentation, the wound dimensions were 6 cm in length,
in width, and 0.5 cm in depth. The wound consisted of 95% of granulation tissue and 5% 6 cm in width,
and 0.5 cm in
slough. Lowdepth. The
levels wound consisted
of exudate of 95%were
(thin, water-like) of granulation
produced. tissue and 5%
Local signs slough.
of infection
Low included
levels ofpain
exudate (thin, water-like) were produced. Local signs of infection
and delayed healing. A wound swab confirmed the presence of Enterococcus included
pain faecalis
and delayed healing.
(resistant A wound swab
to trimethoprim confirmed the
+ sulphonamide, presence
neomycin, of Enterococcus
clindamycin, faecalis
gentamicin;
(resistant to trimethoprim
and sensitive + sulphonamide,
to ampicillin, nitrofurantoin,neomycin, clindamycin,
ciprofloxacin, gentamicin;Pain
and chloramphenicol). and level
sen-
sitive to ampicillin, nitrofurantoin, ciprofloxacin, and chloramphenicol). Pain level was 6
was 6 during the daytime and 8 during treatment. L-Mesitran ® Foam was applied to

during
thethe daytime
wound and6b).
(Figure 8 during
Wound treatment.
dressingsL-Mesitran ® Foam
were performed bywas appliedattohome
the patient the wound
at 72 h
(Figure 6b). Wound
intervals. dressings
Pain levels were
gradually performed
decreased over by the
time andpatient
after 10atdays
home at 72 h intervals.
of treatment, the pain
Pain levels gradually decreased over time and after 10 days of treatment, the painhealed
level during daytime was 0 and 1 during treatment. The wound was completely level
after
during 15 dayswas
daytime of MGH
0 andtreatment
1 during without complications
treatment. The wound(Figure 6c).
was completely healed after 15
days of MGH treatment without complications (Figure 6c).
 Antibiotics 2021, 10, 918 7 of 14
7 of 14
Antibiotics 2021, 10, 918 7 of 14

(a) (b) (c)

Figure 6. Case 6: Venous leg ulcer on the right lower leg. (a) Local finding at initial examination,
(a) day 0 (start of MGH treatment).(b) (c)
(b) Example of L-Mesitran® Foam application. (c) Complete wound
healing on follow-up examination at day 15.
Figure
Figure 6.6.Case
Case6: 6:Venous
Venous leg ulcer
leg ulcer on theon thelower
right rightleg.
lower leg.finding
(a) Local (a) Local finding
at initial at initialday
examination, examination,
0 (start of MGH
treatment). (b) Example of L-Mesitran® Foam application. (c) Complete® wound healing on follow-up examination at day 15.
day 0 (start of MGH treatment).
2.7. Case (b) Example
7: Venous of L-Mesitran Foam application. (c) Complete wound
Leg Ulcer
healing on follow-up examination
2.7. Case at day Leg
A 52-year-old
7: Venous 15.
male patient presented with bilateral venous leg ulcers (Figure 7a).
Ulcer
Relevant comorbidities
A 52-year-old male included
patientCHVI, DM, HT
presented withhyperlipidaemia,
bilateral venoushyperuricemia, morbid
leg ulcers (Figure 7a).
2.7. Case 7: Venous LegRelevant
Ulcer (BMI
obesity 45), and repeated
comorbidities venous
included CHVI,leg ulcers.
DM, HT Previous treatments
hyperlipidaemia, with iodinated
hyperuricemia, pov-
morbid
idone solution for two months were ineffective. Upon presentation, the wound dimen-
A 52-year-old malesionspatient
obesity (BMI 45),
on the presented
right with
and repeated
leg bilateral
venous leg venous legand
ulcers. Previous ulcers
1 cm(Figure
treatments with7a).
iodinated
povidone solution forwere
two 2months
cm in length, 2 cm in width,
were ineffective. Upon in depth.
presentation, theOn the left
wound di-
Relevant comorbidities included CHVI, DM, HT hyperlipidaemia, hyperuricemia, morbid
mensions on the right leg were 2 cm in length, 2 cm in width, and 1 cm in depth. OnThe
leg, the wound dimensions were 10 cm in length, 12 cm in width, and 1 cm in depth. the
obesity (BMI 45), and repeated
wound
left bedvenous
leg, the consisted
wound leg
of ulcers.
dimensions Previous
80% of granulation
were treatments
10 cm tissue
in and 12
length, 20% with
cm iodinated
slough.
in width, and 1pov-
Medium levels
cm in of ex-
depth.
idone solution for two udate
The (thin,
months
wound bed water-like)
were were produced.
ineffective.
consisted of 80%Upon Local signs
presentation,
of granulation of infection
tissue and the included
20%wound pain
slough.dimen- and delayed
Medium levels
healing. A wound swab confirmed the presence of Proteus mirabilis (resistant to ampicillin,
sions on the right leg of
were 2 cm
exudate in length,
(thin, water-like)2 cmwere inproduced.
width, and Local1 cm
signsinofdepth.
infection On the leftpain and
included
aminopenicillin, cefuroxime, trimethoprim + sulphonamide, cefpodoxime,
mirabilisgentamicin,
leg, the wound dimensions
delayedwerehealing.
ciprofloxacin, 10
and cm
A in length,
wound
cefotaxime 12sensitive
swab confirmed
and cm in the width,
to
presence
neomycin,andof1amikacin,
cm in depth.
Proteus The
(resistant to
ceftazidime, mero-
ampicillin, aminopenicillin, cefuroxime, trimethoprim + sulphonamide, cefpodoxime, gen-
wound bed consistedtamicin,
of 80%ciprofloxacin,
penem). of granulation
Staphylococcus tissue
aureus and
(resistant 20%
to slough.
clindamycin; Medium
and sensitive
and cefotaxime and sensitive to neomycin, amikacin, ceftazidime,
levels
to of ex-
trimethoprim +
udate (thin, water-like)sulphonamide,
were produced.
meropenem). norfloxacin, neomycin,
Localaureus
Staphylococcus bacitracin,
signs(resistant
of infection and chloramphenicol).
includedand
to clindamycin; pain Pain
and delayed
sensitive level was
to trimethoprim 5
during daytime and 8 during treatment. L-Mesitran ® Ointment was applied to the wound
healing. A wound swab confirmed the presence of Proteus
+ sulphonamide, norfloxacin, neomycin, mirabilis (resistant to ampicillin,
bacitracin, and chloramphenicol). Pain level
(Figure 7b) and followed by L-Mesitran ® Tulle (Figure 7c) to ensure contact to the wound.
aminopenicillin, cefuroxime, ® trimethoprim
daytime and +8 during sulphonamide,
treatment. cefpodoxime, gentamicin,
was 5 during ®
L-Mesitran Ointment was applied to
Vacutex
the wound(capillary
(Figure 7b) action
anddressing)
followed was applied as® aTulle
by L-Mesitran secondary
(Figuredressing (Figure
7c) to ensure 7d).
contact
ciprofloxacin, and cefotaxime
Dressing and
changes sensitive to
were®performed neomycin, amikacin, ceftazidime, mero-
to the wound. Vacutex (capillary by the patient
action dressing) at home at 48 h intervals
was applied because
as a secondary of the
dressing
penem). Staphylococcus aureus
heavy (resistant
bacterial to
colonization clindamycin;
and moderate and
wound sensitive
exudation.
(Figure 7d). Dressing changes were performed by the patient at home at 48 h intervals to trimethoprim
Pain levels +
gradually de-
creased
sulphonamide, norfloxacin, and
becauseneomycin, after 14 days
of the heavybacitracin, of treatment, the pain
and chloramphenicol).
bacterial colonization level was
and moderate wound 1 during the
Painexudation. daytime
level wasPain and
5 levels2
during treatment. After 14 days of treatment, the interval of dressing changes was pro-
during daytime and 8gradually
duringtotreatment.
longed
decreased and
72 treatment.
h. Since the
L-Mesitran
after 14 days® of
wound
Ointment
became
treatment,was
more superficial,
applied
the pain level wasto the
L-Mesitran
wound
1 during the daytime
® Ointment was

(Figure 7b) and followed

and by L-Mesitran
2
omitted
during
from
® Tulle (Figure 7c) to ensure contact to the wound.
theh.treatment
After
and
14 days of
L-Mesitran
treatment, the interval of dressing
® Tulle was applied and PermaFoam® classic
changes
® Ointment was
was
prolonged to 72 Since the wound became more superficial, L-Mesitran
Vacutex® (capillary action
was used
omitted dressing)
as athe
from was applied
secondary
treatment dressing. as
Theawound
and L-Mesitran secondarywas
® Tulle was dressing
completely
applied and (Figure
healed after7d).
PermaFoam 54 days of
® classic
Dressing changes were MGH
was treatment
performed
used without
by
as a secondary complications
the patient
dressing. at The (Figure
home wound 7e).
at 48 h intervals
was completelybecause healed afterof the54 days of
heavy bacterial colonization and moderate
MGH treatment wound exudation.
without complications (Figure 7e).Pain levels gradually de-
creased and after 14 days of treatment, the pain level was 1 during the daytime and 2
during treatment. After 14 days of treatment, the interval of dressing changes was pro-
longed to 72 h. Since the wound became more superficial, L-Mesitran® Ointment was
omitted from the treatment and L-Mesitran® Tulle was applied and PermaFoam® classic
was used as a secondary dressing. The wound was completely healed after 54 days of
(a) (b) (c)
MGH treatment without complications (Figure 7e).
Figure 7. Cont.

a) (b) (c)
 Antibiotics 2021, 10, 918 8 of 14
Antibiotics 2021, 10, 918 8 of 14

(d) (e)
Figure 7. Case 7: Bilateral venous leg ulcers. (a) Local finding at initial examination, day 0 (start of MGH treatment). (b)
Example of L-Mesitran® Ointment application. (c) Example of L-Mesitran® Tulle application. (d) Example of Vacutex®
application. (e) Complete wound (d)
healing on follow-up examination at day 54. (e)
Figure
Figure 7. 7.Case
Case7:7:Bilateral
Bilateralvenous
venous leg
leg ulcers.
ulcers. (a)
(a)Local
Localfinding
findingatatinitial
initialexamination,
examination,day 0 (start
day of MGH
0 (start treatment).
of MGH (b)
treatment).
Example of 2.8.
L-Mesitran Case 8:
OintmentDiabetic Foot
application. Ulcer
(c) Example of L-Mesitran ®®Tulle application. (d) Example of Vacutex®
(b) Example of L-Mesitran Ointment application. (c) Example of L-Mesitran Tulle application. (d) Example of Vacutex ®
®®

application.(e)(e) Complete wound healingononfollow-up

follow-upexamination
examinationatatday day54.
54.
application. Complete A
wound51-year-old
healing female patient presented with a diabetic foot ulcer on her left foot (Fig-
ure 8a). Relevant
2.8.Case
comorbidities
Case8:8:Diabetic
DiabeticFootFootUlcer
Ulcer
included DM, HT, morbid obesity (BMI 45), and repeated
2.8.
wounds on the right foot due to diabetic foot syndrome. Previous treatments with io-
dinated AA51-year-old
51-year-old female
povidone
female patient
solution patient
for two
presented
presented
months
with
witha diabetic
were
footfoot
aineffective.
diabetic ulcer on her
ulcer
Upon on left
herfoot
presentation,left (Fig-
foot the
ure 8a). Relevant comorbidities included DM, HT, morbid obesity
(Figure 8a). Relevant comorbidities included DM, HT, morbid obesity (BMI 45), and re- (BMI 45), and repeated
woundwoundsdimensions
on theon were
right 5foot
cmdue in length, 3 cm insyndrome.
width, and 1 cm in depth. The wound
peated wounds the right foot to
duediabetic foot
to diabetic foot syndrome. Previous
Previous treatments
treatments withwithio-
consisted of
dinated 90% of
povidone granulation
solution tissue,
for two 5% slough,
months were and 5% epithelialization
ineffective.
iodinated povidone solution for two months were ineffective. Upon presentation, the Upon presentation,tissue. theLow
levelswound
of exudate
wounddimensions (thin,
dimensionswere water-like)
were55cm were
cmininlength, produced.
length,33cm cmin Local
inwidth,
width,andsigns
and 11cm of
cm ininfection
indepth.
depth. Theincluded
The wound
wound pain
and delayed
consisted
consisted healing.
ofof90%90%ofAofgranulation
wound
granulationswab confirmed
tissue,
tissue, 5%slough,
5% the presence
slough, and5%
and of Proteus mirabilis
5%epithelialization
epithelialization tissue.
tissue. (resistant
Low
Low
levelsofofexudate
to ampicillin,
levels exudate(thin,(thin,water-like)
aminopenicillin, water-like) wereproduced.
cefuroxime,
were produced.
trimethoprim Local signs
Local signs of infection
infection included
+ sulphonamide,
of included pain
cefpodoxime,
pain
and
gentamicin delayed
and delayed healing.
ciprofloxacin, A
healing. A wound wound swab
chloramphenicol, confirmed
swab confirmed the
cefotaxime; presence
the presence and of Proteus
sensitive
of Proteus mirabilis
to neomycin,
mirabilis (resistant
(resistant to ami-
to ampicillin, aminopenicillin, cefuroxime, trimethoprim + sulphonamide, cefpodoxime,
kacin,ampicillin,
ceftazidime, ertapenem,
aminopenicillin, and
cefuroxime, meropenem).
trimethoprim Staphylococcus
+ sulphonamide, aureus
cefpodoxime,(resistantgen- to
gentamicin
tamicin ciprofloxacin, chloramphenicol,
ciprofloxacin, cefotaxime; and sensitive to neomycin, ami-
clindamycin, gentamicin;chloramphenicol,
and sensitive tocefotaxime;
trimethoprim and +sensitive to neomycin,
sulphonamide, amikacin,
norfloxacin, ne-
kacin, ceftazidime, ertapenem, and meropenem). Staphylococcus
ceftazidime, ertapenem, and meropenem). Staphylococcus aureus (resistant to clindamycin, aureus (resistant to
omycin, bacitracin,
clindamycin, chloramphenicol,
gentamicin; and fusidic acid,
sensitive to trimethoprim mupirocin) and
+ sulphonamide, Enterococcus faecalis (re-
gentamicin; and sensitive to trimethoprim + sulphonamide, norfloxacin, norfloxacin,
neomycin, bac- ne-
sistant to trimethoprim
omycin,
itracin, + sulphonamide,
bacitracin, chloramphenicol,
chloramphenicol, fusidic acid,fusidicneomycin, clindamycin,
acid, mupirocin)
mupirocin) and Enterococcus gentamicin;
and Enterococcus
faecalis (resistantand(re-
faecalis sensi-
to
tive to ampicillin,
sistant
trimethoprim +nitrofurantoin,
to trimethoprim
sulphonamide, norfloxacin,
+ sulphonamide, bacitracin,
neomycin,
neomycin, clindamycin, ciprofloxacin,
clindamycin,
gentamicin; and chloramphen-
gentamicin;
and sensitive andto sensi-
ampi-
icol).cillin,
Pain level
tive to was 5 during
ampicillin,
nitrofurantoin, the daytime
nitrofurantoin,
norfloxacin, and 8ciprofloxacin,
norfloxacin,
bacitracin, during treatment.
bacitracin, ciprofloxacin, L-Mesitran ® Ointment
and chloramphen-
and chloramphenicol). Pain
icol).
was applied Pain
level wasto level was
the wound
5 during 5 during the
and L-Mesitran
the daytime daytime ®and 8 during treatment.
Foam wasL-Mesitran
and 8 during treatment. L-Mesitran
applied asOintment
® a secondary ® Ointment
dressing.
was applied
towas
Dressing applied
wound to
thechanges theL-Mesitran
were
and wound and
performed ® L-Mesitran
by
Foamthe was
® Foam was applied as a secondary dressing.
patient at home
applied as a at 48 h intervals
secondary dressing. dueDressing
to bacterial
Dressing changes were performed by the patientatat48home at 48 h due
intervals due to bacterial
findings.
changesOn were
day 21, the
performed woundby the dimensions
patient upon presentation
at home h intervals were to1.5 cm infindings.
bacterial length, 0.5
Onfindings.
day 21,Onthe day 21,
wound the wound
dimensions dimensions
upon upon
presentationpresentation
were 1.5were
cm 1.5
in cm
length,in length,
0.5 cm 0.5
in 21
cm in width, and 0.5 cm in depth (Figure 8b). Pain levels gradually decreased and after
cm in and
width, width,0.5 and
cm in0.5depth
cm in (Figure
depth (Figure
8b). Pain8b).levels
Pain levels gradually
gradually decreaseddecreased
and afterand 21 after
days21
days of treatment, the pain level was 1 during the
the daytime andduring
duringtreatment.
treatment. TheThe
ofdays of treatment,
treatment, the pain thelevel
pain level
was was
1 during 1 during
the daytime daytime and
and during treatment. The inter-
interval
val of the
interval dressing
of theofdressing
the dressing changes
changeschanges was
waswas prolonged
prolonged
prolonged to 72
to 72
to 72 h and
h and
h and continued
continuedwith
continued with applying
withapplying
applying only only only
L-Mesitran ®
L-Mesitran
L-Mesitran Foam. ®
® Foam. TheThe
Foam. wound
The wound
wound was was
was completely
completelyhealed
completely healed after
healed 44days
after 44
after 44 daysof
days ofof MGH
MGH
MGH treatment
treatment
treatment
without complications
without complications (Figure
without complications (Figure 8c). (Figure8c).8c).

(a) (b) (c)

(a) 8: Diabetic foot ulcer on the left (b)
Figure 8. Case (c)
foot. (a) Local finding at initial examination, day 0
(start of MGH treatment). (b) Follow-up examination at day 21. (c) Complete wound healing on
Figure 8. Case
Figure 8: Diabetic
8. Case footfoot
8: Diabetic ulcer onon
ulcer the
theleft
leftfoot.
foot. (a)
(a) Local findingatatinitial
Local finding initial examination,
examination, dayday
0 0
follow-up examination at day 44.
(start of MGH treatment). (b) Follow-up examination at day 21. (c) Complete wound healing on
(start of MGH treatment). (b) Follow-up examination at day 21. (c) Complete wound healing on
follow-up examination
follow-up at day
examination 44.44.
at day
8 9 of 14

2.9. Case 9: Venous Leg Ulcer

Antibiotics 2021, 10, 918 9 of 14
A 49-year-old male patient presented with a venous leg ulcer at his right lower leg
(Figure 9a). Relevant comorbidities included DM, HT, hyperlipidaemia, and a medical
history of thrombosis 2.9.of
Casethe right lower
9: Venous Leg Ulcerleg without acute signs of ischemia. Previous
treatments with antiseptic dressing with
A 49-year-old silver presented
male patient nanoparticles
with a for seven
venous leg weeks were
ulcer at his inef-
right lower leg
fective. Upon presentation,
(Figure 9a).theRelevant
woundcomorbidities
dimensionsincludedwere 5DM, cm HT,
in length, 3 cm in and
hyperlipidaemia, width,
a medical
and 1.5 cm in depth.history
The wound consisted
of thrombosis of 90%
of the right lowerofleg
granulation
without acutetissue,
signs of5% slough,
ischemia. and treat-
Previous
ments with antiseptic dressing with silver nanoparticles for seven weeks were ineffective.
5% epithelialization tissue. Low levels of exudate (thin, water-like) were produced. Local
Upon presentation, the wound dimensions were 5 cm in length, 3 cm in width, and 1.5 cm in
signs of infection included
depth. The pain,
wound malodour,
consisted ofand delayed
90% of healing.
granulation tissue, A
5% wound
slough, andswab con-
5% epithelializa-
firmed the presence oftionEnterococcus faecalis
tissue. Low levels (resistant
of exudate (thin,to trimethoprim
water-like) + sulphonamide,
were produced. Local signs ofne-infection
omycin, clindamycin, gentamicin;
included and sensitive
pain, malodour, and delayedto ampicillin, nitrofurantoin,
healing. A wound swab confirmed bacitracin,
the presence of
ciprofloxacin, chloramphenicol). Pain(resistant
Enterococcus faecalis level was 5 during the
to trimethoprim daytime and neomycin,
+ sulphonamide, 8 during clindamycin,
treat-
gentamicin; and sensitive to ampicillin, nitrofurantoin, bacitracin, ciprofloxacin, chloram-
ment. L-Mesitran Soft
® (MGH) was applied to the wound and L-Mesitran Foam (Figure ®
phenicol). Pain level was 5 during the daytime and 8 during treatment. L-Mesitran® Soft
9b) was applied as a (MGH)
secondary dressing.
was applied Dressing
to the wound andchanges were®performed
L-Mesitran Foam (Figure by9b)the patient
was applied as a
at home at 48 h intervals. Paindressing.
secondary and malodour
Dressinglevels
changesgradually decreased
were performed by theand afterat14home
patient daysat 48 h
of treatment, the painintervals.
was absent Pain during the daytime
and malodour (VAS score
levels gradually of 0) and
decreased andafter
at level 1 during
14 days of treatment,
the pain ® was absent during the daytime (VAS score of 0) and at level 1 during treatment.
treatment. Only L-Mesitran Foam® was applied. The wound was completely healed after
Only L-Mesitran Foam was applied. The wound was completely healed after 17 days of
17 days of MGH treatment without
MGH treatment complications
without complications (Figure 9c).
(Figure 9c).

(a) (b) (c)

Figure
Figure 9. 9. Case
Case 9: Venous
9: Venous leg on
leg ulcer ulcer on the
the right right
lower leg. lower leg.
(a) Local (a) Local
finding finding
at initial at initial
examination, dayexamination,
0 (start of MGH
day 0 (start of MGH treatment). (b) Example of L-Mesitran Foam application. (c) Complete wound
treatment). (b) Example of L-Mesitran ® Foam application. (c) Complete wound
® healing on follow-up examination at day 17.
healing on follow-up examination at day 17.
3. Discussion
In all presented cases, the healing process was positively affected; the wound bed was
3. Discussion cleansed; and the pain, odour, and exudation were completely eliminated. Despite the
In all presentedproven
cases,microbial
the healingburdenprocess was positively
in the wound by means ofaffected;
swab and the woundexamination,
cell culture bed
was cleansed; and the pain, odour, and exudation were completely eliminated. Despiteof local
antibiotic treatment was not initiated and treated locally with only MGH. Signs
infection were eliminated by the effect of MGH in the applied materials. In eight out of
the proven microbialnineburden in the
cases, the woundwound
non-healing by means of swab healed.
was completely and cell In culture examina-
one case (case 5) treatment
tion, antibiotic treatment
with MGHwascontinues.
not initiated andeven
However, treated locally
in this with
case, there wasonly MGH. improvement
a significant Signs of in
local infection were eliminated by the effect of MGH in the applied materials. In eight out
the local finding, but due to the low patient compliance, we have no further information.
of nine cases, the non-healing
After proper wound waspatients
training, the completely
were ablehealed. In one
to perform case (case
the wound 5) treat-
dressings themselves
or with the help of family members at home, and they all considered it easy. No adverse
ment with MGH continues. However, even in this case, there was a significant improve-
effects of the applied topical material with MGH were observed.
ment in the local finding, Thebut due
costs of to the low
wound patient in
management compliance, we have
developed countries areno further
around 1–4% in-of total
formation. After proper
healthtraining, the patients
care expenditure were
[15,28]. The able
number to perform the wound
of non-healing wounds dressings
is expected to in-
themselves or with the help of family members at home, and they all considered itmellitus,
crease, due to longevity and comorbidities, such as obesity and diabetes easy. and
No adverse effects of the applied topical material with MGH were observed.
hence, elevate economic impact [2,29,30]. MGH enables a faster healing process and can
resolve local infections without the need for antibiotic treatment, and thus forms a potent
The costs of wound management
alternative treatment. in developed countries are around 1–4% of total
health care expenditureA[15,28].
total of The numberwith
nine patients of non-healing
wounds of various wounds is expected
aetiologies to in- in the
were included
crease, due to longevity
study. and
MGH comorbidities,
promoted autolyticsuchdebridement,
as obesity led and to diabetes
the cleansing mellitus, and bed,
of the wound
hence, elevate economic impact [2,29,30]. MGH enables a faster healing process and can
and induced granulation tissue formation and epithelialization. This is in line with pre-
vious studies [14,31]. Debridement and cleansing can be attributed to the moist wound
resolve local infections without the need for antibiotic treatment, and thus forms a potent
alternative treatment.
A total of nine patients with wounds of various aetiologies were included in the
study. MGH promoted autolytic debridement, led to the cleansing of the wound bed, and
induced granulation tissue formation and epithelialization. This is in line with previous
Antibiotics 2021, 10, 918 10 of 14

environment, its acidification, the osmotic activity, and oxygenation of the wound en-
vironment [14,31,32]. The prevalence of biofilms in non-healing wounds is estimated
to be approximately 60% [33,34]. Biofilms have a high capacity for bacterial resistance
and show increased resistance to host cellular responses and antiseptics [15,35]. MGH
is effective in removing coating and necrosis from the wound bed, and thus may work
in cases where antibiotics are ineffective [24]. Furthermore, MGH was also effective in
eradicating MRSA in venous leg ulcers, so antibiotic-resistant strains can also be eliminated.
The broad-spectrum antimicrobial activity of MGH on Staphylococcus aureus, Pseudomonas
aeruginosa, and Streptococcus pathogens have been also confirmed by others [21,31,36]. Due
to its antimicrobial mechanisms, including acidic pH, osmotic activity, and slow release
of hydrogen peroxide, MGH is effective against a wide range of pathogens, including
multi-resistant bacteria, fungi, and viruses [13,37,38]. Moreover, the use of MGH in wound
management can reduce the use of antibiotics and topical antiseptics [32]. Repeated use of
MGH materials is without risk of developing resistance [13,21]. In our study, all patients
had local signs of infection and microbial burden in the wound bed was proven in eight
out of nine patients (wound swab was not taken in one case). Antibiotic treatment was
required in none of the cases. We have verified that topical treatment with MGH is a safe
and easy-to-use alternative method for treating local infections. MGH has antimicrobial,
antioxidant, and anti-inflammatory properties and is thus ideal for the treatment of infected
wounds [14,39,40].
Alleviation of unpleasant symptoms that accompany non-healing wounds is important
to improve the quality of a patient’s life [5]. Pain has not only a sensory component, but also
an emotional component, which is associated with anxiety, depression, aggression, feelings
of danger, helplessness, hopelessness, and loss of motivation [41,42]. Patients with wounds
can also suffer from procedural pain [43]. Stress experienced during wound management
increases cortisol levels, and this has a negative effect on wound healing [44,45]. In all
patients, the pain was alleviated or eliminated after the first dressing change and the
intensity of procedural pain was reduced. In all patients, the need for analgesic treatment
was gradually reduced or eliminated. As supported by others, this can be attributed to
the MGH that prevents incorporation of the wound dressing into the wound bed and
subsequent damage of the new granulation during wound dressing [14,21].
Odour is another unpleasant symptom of infection in non-healing wounds. Wound
odour has a negative effect on the patient’s psyche, is usually associated with abundant
production of exudate, and the two factors can lead to social isolation of the patient [21].
In our study, a reduced odour and exudate was noticeable after the first dressing change
(the shortest dressing interval was two days and odour and exudate disappeared after
approximately 16 days of treatment). Only in patient number 5 was maceration of the
wound edges (0.5 cm from the wound edge) observed. We believe that the patient applied
a large amount of L-Mesitran® Ointment to the wound and did not refresh the dressings
frequently enough, which led to the accumulation of exudate in the secondary bandage
and, subsequently, maceration. Therefore, it is always important to check exudate levels
regularly and change dressings accordingly. After training, this issue was partially resolved,
but there was low compliance in this patient. The high sugar content of MGH attracts
lymph fluid and wound exudate out of the tissue and helps in the removal of exudate
into the dressing [21]. This process, together with the anti-inflammatory activity of MGH,
subsequently reduces oedema and pain [21]. Wound odour is produced by bacteria that
metabolize serum, tissue proteins, and dead cells, leading to amino acid production and
unpleasant odour [46,47]. Glucose in MGH acts as an alternative odourless substrate
for these bacteria and thus eliminates odour [21,32,46,47]. In addition, the antimicrobial
activity of honey will reduce the number of bacteria in the wound, thereby reducing
odour [46,48]. This property is most evident within 24 h after the application of honey to
the wound [49]. Also, in our study, patients reported a reduction in odour already after the
first wound dressing (the shortest dressing interval was two days). Due to the beneficial
healing, it was possible to extend the intervals between the individual dressings to up
Antibiotics 2021, 10, 918 11 of 14

to four days. This of particular importance during the COVID-19 pandemic, when the
availability of health services and personal contact with patients is really limited and often
replaced by online or phone consultations. In order to get the best result, it is essential
that the patients and their relatives cooperate with the treatment regimen and the hygiene
measurements. Keeping them involved, maintaining regular appointments, and seeing
progression in different aspects (odour, pain, wound progression) helps to keep the patients
motivated. Non-healing wounds are an economic burden on healthcare systems. Extending
the time between wound dressings, shortening the wound healing time, not administering
antibiotics, and providing the ability to perform wound dressings at home (natural social
environment or with the help of home care nurses) can significantly reduce the costs. MGH
should be considered when non-healing wounds stay stagnant.

4. Materials and Methods

Patient Selection
In a prospective observational study, MGH was applied to a selected group of patients
with non-healing wounds. Inclusion criteria were having a non-healing wound with
treatment lasting more than 6 weeks, type 2 diabetes mellitus, presence of local signs of
inflammation, absence of systemic sings inflammation, pain including procedural pain,
and patient agreement. Exclusion criteria were having an allergy to bee stings or MGH,
systemic signs of inflammation, and patient disagreement.
A total of nine patients were included in the study, of which six were men and three
women, the average age was 57 years (minimum 43 and maximum 75, with a median
of 54 years). Six patients had leg ulcers, two had diabetic foot syndrome, and one had
a dehisced surgical wound. Previous therapy consisted of iodine material in six cases,
bioceramic dressing in one patient, and nano-silver material in two patients. All patients
showed local signs of wound infection and signs of systemic infection were absent. The
average assessment of pain intensity during the day reached 5.1 points and procedural
pain averaged 7.1 points according to VAS. Most patients (n = 8) received oral analgesic
treatment during the initial phase of wound treatment until pain levels were minimal—
detailed descriptions about the pain level are part of the case summaries. In one patient,
the pain was not pharmacologically treated, diabetic neuropathy was present.
Wound swabs were taken using the Levine technique upon first presentation to
determine bacterial colonization [50]. Standard laboratory protocols and molecular testing
using matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-
ToF MS) were followed to identify the microorganisms and to determine their susceptibility
and resistance profiles [51].
Wound characteristics and relevant patient information from the presented nine cases
are summarized in Supplementary Table S1. Basic information about the patient, local
assessment of the non-healing wound, pain, and the presence and cause of infection are
available. Since all wounds were non-healing and locally infected, topical treatment with
L-Mesitran was recommended.

5. Conclusions
In our prospective case series, we confirmed in a group of nine patients on an out-
patient basis that MGH treatment has beneficial effects on the healing process of infected
non-healing wounds of various aetiologies. The application of an MGH-containing dress-
ing led to the activation of the healing process, stimulation of debridement, and a faster
cleansing phase of the wound bed. MGH reduced odour and exudate secretion and main-
tained an optimal moist wound bed environment. Wound-related pain and procedural
pain were significantly reduced and analgesia was reduced or stopped in all patients.
Despite the local signs of infection and the presence of different microorganisms, MGH was
effective to resolve infection, and thus replaced the need for antibiotics. Topical treatment
of non-healing wounds with MGH dressing led to a lower frequency of wound dressings
at home and lower financial costs of care. The healing and reduction in symptoms strongly
Antibiotics 2021, 10, 918 12 of 14

improved the patients’ quality of life. MGH forms an attractive alternative to antibiotics to
fight infections while enhancing the wound healing trajectory.

Supplementary Materials: The following are available online at https://www.mdpi.com/article/10

.3390/antibiotics10080918/s1. Table S1: Overview of the presented cases.
Author Contributions: Conceptualization, A.H. and A.P.; methodology, A.H. and A.P.; validation,
L.C. (Lucie Chlupáčová) and L.C. (Lada Cetlová); investigation, A.H. and A.P.; data curation, A.H.,
L.C. (Lucie Chlupáčová), and A.P.; writing—original draft preparation A.H.; writing—review and
editing, L.C. (Lucie Chlupáčová), L.C. (Lada Cetlová), N.A.J.C. and A.P.; supervision, A.P.; project
administration, A.H. and A.P.; final approval of the manuscript, all authors. All authors have read
and agreed to the published version of the manuscript.
Funding: This research received no external funding.
Institutional Review Board Statement: The study was conducted according to the guidelines of the
Declaration of Helsinki. Anonymized data were collected from study participants and processed in
accordance with Act No. 101/2000 Coll. of valid legislation of the Czech Republic. The study was
approved by the local ethics committee (the approval does not include the IRB number from the
ethics committee, which is common practice in the healthcare facility involved).
Informed Consent Statement: The patients were informed about the study, and they all gave written
consent to use their photos and data for publication, providing their anonymity was guaranteed. The
principles of the World Medical Association’s Declaration of Helsinki were followed.
Data Availability Statement: The data that support the findings of this study are available from the
corresponding author upon reasonable request. All data relevant to the study are included in the
article. The data are safely stored as requested by Czech legislation in healthcare provider secured
electronic system.
Acknowledgments: Authors would like to thank to all the patients involved in the study.
Conflicts of Interest: N.A.J.C. is employed by Triticum Exploitatie BV, the manufacturer of the
MGH-based product used in this study. However, he was not involved in the design of the study; the
collection, analysis, or interpretation of the data; and the presentation of the results. He was solely
consulted for his experience and expertise with MGH. All other authors declare no conflict of interest.

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