The Susceptibility Pattern of Staphylococcus Aureus and
Streptococcus Pyogenes to Fusidic Acid and Mupirocin in Superficial
Pyoderma
Amalia Rizkha Malini
1
, M. Athuf Thaha
2
, Fitriani
3
1
Dermatovenereologist from Department of Dermatology and Venereology Faculty of Medicine Sriwijaya University/Dr.
Moh. Hoesin General Hospital Palembang, Jendral Sudirman Street Km 3.5, Palembang, South of Sumatera, Indonesia
2
Professor of
Department of Dermatology and Venereology Faculty of Medicine Sriwijaya University/Dr. Moh. Hoesin
General Hospital Palembang, Jendral Sudirman Street Km 3.5, Palembang, South of Sumatera, Indonesia
3
Staff of
Department of Dermatology and Venereology Faculty of Medicine Sriwijaya University/Dr. Moh. Hoesin General
Hospital Palembang, Jendral Sudirman Street Km 3.5, Palembang, South of Sumatera, Indonesia
Keywords: susceptibility pattern, fusidic acid, mupirocin, Staphylococcus aureus, Streptococcus pyogenes
Abstract: The most common causes of superficial pyoderma are Staphylococcus aureus (S. aureus) and Streptococcus
pyogenes (S. pyogenes). Currently, many regions have reported of S. aureus and S. pyogenes resistance to
fusidic acid and mupirocin, whereas there are regions that still susceptible. Antibiotic resistance is a health
issues in many countries, which increase the morbidity and mortality. The susceptibility test is one of methods
to determine the resistance problems. About 27 and 12 of S. aureus and S. pyogenes isolates, consecutively,
were collected from 44 specimen samples of superficial pyoderma patients. All isolates were subjected to
susceptibility test to fusidic acid and mupirocin using broth microdilution methods. This study showed
differences between S. aureus to fusidic acid versus mupirocin, whereas S. aureus 8 times more susceptible
to fusidic acid than mupirocin significantly (PR = 8.312; p = 0.001); S. pyogenes is more susceptible to fusidic
acid than mupirocin significantly (p = 0.000). This study has been show Staphylococcus aureus and S.
pyogenes are more susceptible to fusidic acid than mupirocin
1 INTRODUCTION
Superficial pyoderma is a bacterial skin infection that
affects the epidermis, beneath the stratum corneum
and hair follicles (Nirwati,2013). Approximately
30% of superficial pyoderma in developing countries
occurs at below 15 years old (Depari, 2016). The 14
meta analysis collected by World Health
Organization (WHO), reported that in tropical
countries superficial pyoderma primarily caused by
Staphylococcus aureus (S. aureus) and Streptococcus
pyogenes (S. pyogenes), whereas in developing
countries is S. aureus (Depari, 2016). Inadequate
superficial pyoderma therapy may lead to
complications either extending to the layer beneath
the epidermis or other organs, therefore requiring
immediate empirical therapy (Milet, 2012). Empirical
therapy can trigger antibiotic resistant of bacterial
strains and treatment failure, especially when used
irrationally. The widespread use of topical antibiotics
is one of the causes of antibiotic resistance
(Poovelikunnel, 2015) (Antonov,2015)
Currently various studies have reported resistance
of S. aureus and S. pyogenes both to fusidic acid and
mupirocin in various regions, but there are still
regions where S. aureus and S. pyogenes are
susceptible to both agent (Koning,2012) The
objective of this study is to determine the
susceptibility of S. aureus and S. pyogenes to fusidic
acid and mupirocin in Dermatology and Venereology
Policlinic of Dr. Mohammad Hoesin General
Hospital Palembang and analyzed the differences
between S. aureus and S. pyogenes susceptibility to
fusidic acid and mupirocin
2 METHODS
This is an observational analytical laboratory study
with cross sectional design conducted from July to
October 2017 at Dermatologic Infection Division,
DV Department, Clinical Pathology and
Microbiology Department of Dr. Mohammad Hoesin
Malini, A., Thaha, M. and Fitriani, .
The Susceptibility Pattern of Staphylococcus Aureus and Streptococcus Pyogenes to Fusidic Acid and Mupirocin in Superficial Pyoderma.
DOI: 10.5220/0008154502270230
In Proceedings of the 23rd Regional Conference of Dermatology (RCD 2018), pages 227-230
ISBN: 978-989-758-494-7
Copyright
c
2021 by SCITEPRESS – Science and Technology Publications, Lda. All rights reserved
227
General Hospital Palembang, and Health laboratory
for Palembang. The 44 study samples that fullfiled the
inclusion criteria, then were subjected to culture
examination and identified. Each S. aureus and S.
pyogenes isolates that grow later were subjected to
susceptibility test using broth microdilution methods.
3 RESULTS
The study samples included in this study from < 1
to15 years old, majority of the subjects (59.1%) were
in the 1-5 years old group, with same ratio of male
and female (1:1). The majority of the subjects
(36.4%) of this study was in the middle
socioeconomic level and poor environmental
conditions (27.4%). The sample of this study mostly
normoweight (70.5%). A total of 30 subjects (68.2%)
using antibiotics where as 11 subjects using
appropriate antibiotics questioned by researchers i.e
amoxicillin, chloramphenicol, and gentamicin. Based
on clinical manifestation, the majority of diagnosis
found in the study sample was vesicobullous impetigo
(38.6%) (Table 1).
Table 1. Sosiodemografic characteristic of sample
Characteristic N %
Age (years old), mean ± SD 5,02±3,65
Age
< 1 years old
1 - 5 years old
6 - 10 years old
10
15
y
ears old
3
26
11
4
6,8
59,1
25,0
9,1
Sex, n (%)
Male
Female
22
22
50
50
Sosioeconomic Condition
Low
Middle
High
Very high
13
16
12
3
29,5
36,4
27,3
6,8
Environment
Good
Poo
r
27
17
61,4
38,6
Body Mass Index
Underweight
Normoweight
Overweight
10
31
3
22,7
70,5
6,8
Among 44 specimens obtained from 44 subjects,
48 isolates were found in culture, 4 of which were
mixed. The most bacteria found were S. aureus, 27
isolates (61,3%) and S. pyogenes 12 isolates (27,2%).
The susceptibility test for fusidic acid, found that
77.8% of S. aureus isolates and all S. pyogenes
isolates (100%) were susceptible to fusidic acid
(Table 2). While, susceptibility test result for
mupirocin showed that 29.6% isolates of S. aureus
susceptible to mupirocin and only 8.3% of S.
pyogenes isolates were susceptible to mupirocin
(Table 2). There was a difference between S. aureus
susceptibility to fusidic acid and mupirocin, with S.
aureus 8 times more susceptible to fusidic acid than
mupirocin significantly (Table 3). In addition, S.
pyogenes are more susceptible to fusidic acid than
mupirocin significantly (Table 4).
RCD 2018 - The 23rd Regional Conference of Dermatology 2018
228
Table 2. Susceptibility of S. aureus dan S. pyogenes to fusidic acid and mupirocin
Antibiotic S. aureus S. pyogenes
Susceptible Resistant Susceptible Resistant
Fusidic acid 21 (77,8) 6 (22,2) 12 (100) 0 (0)
Mupirocin 8 (29,6) 19 (70,4) 1 (8,3) 11 (91,7)
Table 3. Comparasion of S. aureus susceptibility between fusidic acid to mupirocin
Characteristic Susceptibility of S. aureus
Total
PR*
(CI 95%)
p value*
Susceptible Resistant
Antibiotic
Fusidic acid
Mupirocin
21
8
6
19
27
27
8,312
(2,437-28,354)
0,001
Total 29 25 54
*chi-square test
Table 4. Comparasion of S. pyogenes susceptibility between fusidic acid to mupirocin
Chracteristic Susceptibility of S. pyogenes
Total
PR*
(CI 95%)
p value*
Susceptible Resistant
Antibiotic
Fusidic acid
Mupirocin
12
1
0
11
12
12
-
0,000
Total 13 11 24
* Fisher’s exact test
4 DISCUSSION
The incidence of superficial pyoderma is influenced
by host factors (immune status and skin barrier state),
environment and agent (Nirwati,2013) (Milet, 2012).
Predisposing factors are associated with superficial
pyoderma, including age, sex, socioeconomic status,
environmental condition, and nutritional status of the
patient (Depari,2016) (Karimkhani,2014)
The results of this study indicate that S. aureus
and S. pyogenes are still sensitive to fusidic acid and
have good in vitro effectiveness. Low susceptibility
of S. aureus and S. pyogenes to mupirocin in this
study, suggesting in vitro resistance of S. aureus and
S. pyogenes to mupirocin. Susceptibility patterns are
influenced by factors including geographic factors
(environmental contamination, population density,
and population migration), socioeconomic,
prevalence of MRSA or antibiotic resistant bacteria,
and antibiotic usage
7,12
. Antonov et al., Found a
strong association between mupirocin resistance and
some factors were: history of mupirocin use (19.2% -
26.5%, p <0.001), MRSA isolates (55.4%, p <0.001),
and history of other topical and systemic antibiotics
(OR 3.6, p <0.006) (Antonov, 2015)
Mupirocin resistance is caused by point mutations
in the ileS gene, as well as the transmission of MupA
or MupB genes via plasmid-mediated intergene
bacteria to form gene modification ileS. This
modification gene is the form of "eukaryotic-like"
genes RNA synthetase that has no affinity for
mupirocin
6
. MupA genes are also known to be present
in plasmids bacteria that are resistant to some other
antibiotics that may cause cross resistance with other
antibiotics via a plasmid conjugation mechanism.
(Poovelikunnel, 2015) (Cadilla, 2011)
High resistance of S. aureus and S. pyogenes
isolates to mupirocin versus fusidic acid in this study
may be due to antibiotic usage (Poovelikunnel,2015)
(Cadilla, 2011)The use of antibiotics with chemical
structures resembling mupirocin is known to cause
horizontal transfer between bacterial carriers of
resistant genes against the antibiotic. Candilla et al.,
found that the MupA gene was strongly associated
with MDR (p <0.0001), 23% among 837 antibiotic-
resistant samples of the β-lactam and non-β-lactam
groups were MupA carriers. In addition mupirocin-
The Susceptibility Pattern of Staphylococcus Aureus and Streptococcus Pyogenes to Fusidic Acid and Mupirocin in Superficial Pyoderma
229
resistant bacteria had a 9-fold (OR 9.83%) risk for
resistance to at least 4 β-lactam and non-β-lactam
antibiotics (erythromycin, tetracycline,
chloramphenicol, gentamicin, ofloxacin, or
trimethoprim-sulfamethoxazole). (Cadilla, 2013)
Fusidic acid has a unique and very different
chemical structure. The carbon chains in the chemical
structure of fusidic acid are similar to steroids than
antibiotics so rarely cause cross-resistance
10
. The in
vitro efficacy of antibiotics is more significant if
proven to be in vivo. In vitro sensitivity is not entirely
predictable for in vivo effect. In addition, in vitro
resistance is common, but not necessarily related to
treatment failure
(McNeil,2014)
5 CONCLUSION
The results of this study showed that there has been
in vitro resistance of S. aureus and S. pyogenes to
mupirocin. In addition, S. aureus and S. pyogenes are
more susceptible to fusidic acid than mupirocin. In
vitro effectivity of fusidic acid was better than
mupirocin. The emergence of resistance in this study
is influenced by various factors, especially the use of
antibiotics that causes cross resistance between
bacterial carrier resistant genes.
ACKNOWLEDGEMENTS
The authors would like to thank Dr. dr. M.
Zulkarnain, ScPKK and dr. Lisa Dewi, M. KEs who
assist in the effort of this research. The authors also
would like to Department of Dermatology and
Venereology, and Faculty of Medicine of Sriwijaya
University.
REFERENCES
Antonov NK, Garzon MC, Morel KD, Whittier S, Planet
PJ, Lauren CT. 2015. High prevalence of mupirocin
resistance in Staphylococcus aureus isolates from a
pediatric population. AAC; 59(6): 3350-56.
Cadilla A, David MZ, Daum RS, Vavra SB. 2011.
Methicillin-resistant of high-level mupirocin resistance
and Multidrug-resistant Staphylococcus aureus at an
Academic Center in the Midwestern United States. J
Clin Microbiol; 49(1): p. 95-100.
Caft N. 2012. Superficial cutaneous infections and
pyodermas.. In: Goldsmith LA, Katz SI, Gilchrest BA,
Paller AS, Leffell DJ, Wolff K, editors. Fitzpatrick’s
Dermatology in General Medicine. 8
th
ed. New York:
The Mc Graw-Hill Companies, Inc;. p. 2128-60.
Depari LI, Sugiri U, Ilona L. 2016. Relation between risk
factors of pyoderma and pyoderma incidence. AMJ;
3(3): 434-39.
Karimkhani C, Boyers LN, Prescott L, Weich V, Delamere
FM, Nasser MZ, et al. 2014. Global burden of skin
sisease as reflected in Cochrane database of systematic
riview. JAMA Dermatol; 150(9): 945-51.
Koning S, Van Der Sande R, Venagen AP, Van Suijlekom-
Smit LWA, Morris AD, Butler CC, et al.2012.
Intervention of Impetigo (review). Cochrane Database
Systematic Review issue 1. Amsterdam: John Wiley &
Sons.
McNeil JC, Hulten KG, Kaplan SL, Mason EO. 2014.
Decreased susceptiblities to ratapamulin, mupirocin,
and chlorhexidine among Staphylococcus aureus
isolates causing skin and soft tissue infections in
otherwise healthy children. Antimicrob Agents Chem;
58(5): 2878-83.
Milet CR, Halpern AV, Reboli AC, Heymann WR. 2012.
Bacterial diseases. In: Bolognia Jl, Jorizzo JL, Rapini
RP, Schaver JV, editors. Dermatology. 3
rd
ed.
Edinburg: Mosby; p. 1887-1220.
Mohajeri P, Ghalamine B, Rexaei M, Khamisabadi Y.
2012. Frequency of mupirocin resistant Staphylococcus
aureus strains isolated from nasal carriers in hospital
in Kermanshah. Jundisphapus J Microbiol; 5(4): 560-
63.
Nirwati H, Radiono S, Ariwibowo L, Hananta IPY, Tama
LGY, Danarti R. 2013. Sensitivity pattern of S. aureus
isolated from children with pyoderma againts various
antibiotics in Waingapu, Sumba Nusa Tenggara Timur.
In: Nirwati H, Dewi NYA. Proceeding of DAAD-
IGHEP Maternal and Child Health Summer School.
Bali: Udayana University Press; p. 195-203.
Paudel U, Parajuli S, Pokhrel DB. 2013. Clinico-
bacteriological profile and antibiotic sensitivity pattern
in pyodermas: a hospital based study. Nep J Lepr;
11(1): 49-58.
Poovelikunnel T, Gethin G, Humphreys H. 2015.
Mupirocin resistance: clinical implications and
potential alternatives for the eradication of MRSA. J
Antimicrob chem; 70: 2681-92.
Sanchez CE, Moore LSP, Husson F, Holmes AH. 2016.
What are the factors driving antimicrobial resistance?
Perspective from a public event in London, England.
BMC infec Dis; 16(465): 1-5.
RCD 2018 - The 23rd Regional Conference of Dermatology 2018
230