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http://www.medigraphic.com/pdfs/lamicro/mi-2006/mi061d.pdf
Revista Latinoamericana de
MICROBIOLOGÍA
Vol. 48, No. 1
January - March. 2006
pp. 14 - 16
ORIGINAL ARTICLE
Antimicrobial susceptibility of strains of Propionibacterium acnes isolated from inflammatory acne
Walter Gübelin,*,** M. Angélica Martínez,*** M. Teresa Molina,* Solange Zapata,*
M. Eugenia Valenzuela****
ABSTRACT. In the last decade, a significant increase in the antimicrobial resistance of clinical specimens of Propionibacterium acnes
to first line antibiotics used for acne treatment, has been informed
in Europe and in the USA. No information about strains isolated
from Latin-American countries is available. The antimicrobial susceptibility of 53 strains of P. acnes isolated from skin specimens of
inflammatory acne patients, at the clinical Hospital University of
Chile was tested. All isolates were susceptible to penicillin, minocycline, and nadifloxacin. Erythromycin and clindamycin resistance
was found in 3.8 and 1.9% isolates respectively. Resistance to lymecycline was observed in one isolate, which was intermediate to
tetracycline and doxycycline.
RESUMEN. En la última década se ha informado un aumento significativo en la resistencia de Propionibacterium acnes a antimicrobianos de primera línea para el tratamiento del acné, en Europa y
Estados Unidos. No existe información sobre la susceptibilidad antimicrobiana de cepas de este microorganismo aisladas en Latinoamérica. Se determinó la susceptibilidad antimicrobiana de 53 cepas de P. acnes aisladas de lesiones de piel de pacientes con acné
inflamatorio, atendidos en el Hospital clínico de la Universidad de
Chile. Todas las cepas fueron susceptibles a penicilina, minociclina
y nadifloxacina, observándose resistencia a eritromicina y clindamicina en 3.8 y 1.9% cepas respectivamente. Una cepa fue resistente a limeciclina, pero intermedia a tetraciclina y doxiciclina.
Key words: Antimicrobial susceptibility, Propionibacterium acnes,
inflammatory acne.
Palabras clave: Susceptibilidad, Propionibacterium acnes, acné inflamatorio.
Propionibacterium acnes is an anaerobic, non-motile,
non-sporulating Gram-positive, bacillus, found as part of
the cutaneus comensal microbiota.1 It is frequently isolated as contaminant in clinical specimens, but it is also
found as primary pathogen in patients with predisposing
factors, specially foreign-body implants, diabetes, and previous surgery.2,3 Severe clinical syndromes include sepsis,
neurosurgical infections, endocarditis, arthritis and endophtalmitis.2,3 The role of P. acnes in the etiology of inflammatory acne is widely accepted.1,4 Acne is a common
skin disease, affecting mainly adolescents and young
adults, worldwide. The disfiguring skin sequelae which
sometimes accompany this disease may have an important
impact in the psychological health of young people.5 The
treatment of acne involves the empirical use of antimicrobials. However, in the last years several studies have documented the increase in the prevalence of antimicrobial resistance, particularly to macrolides, clindamycin and to
the tetracyclines.6-8 The objective of this study was to determine the antibiotic susceptibility of strains of P. acnes
strains isolated from patients with inflammatory acne.
Between March and October 2001, 53 strains of P. acnes obtained from skin specimens of patients with inflammatory acne, presenting at the clinical hospital of the University of Chile were studied. Patients had not received
antibiotics in the previous 3 weeks, nor have been treated
for acne before enrolment, and gave informed consent for
taking clinical specimens. Strains were grown on sheep
blood agar plates supplemented with hemin (5 µg/ml) and
vitamin K (0.5 µg/ml), in an anaerobic system (Oxoid,
Ltd., United Kingdom) at 36ºC for 96 h. Strains were identified based on conventional criteria including cell and
colonial morphologies, production of catalase and indole,
and nitrate reduction. The organisms did not hydrolyzed
esculin or urea, and did not fermented maltose or sucrose.
Antimicrobial susceptibility testing was performed by
the NCCLS reference agar dilution method by using brucella agar (Difco Laboratories, Detroit, Mich.) supplemented with 5% lysed horse blood.9 Standard powders
were obtained from the following manufacturers: penicillin G, Laboratorio Chile, erythromycin and tetracycline,
Sigma Chemical (St. Louis, Mo.), doxycycline and minocycline, Pfizer Inc., clindamycin, Pharmacia Upjohn,
nadifloxacin and lymecycline, Laboratorio Galderma,
Chile. The inocula were prepared by suspending colonies from 48 h culture plates in brucella broth to achieve
a density equivalent to a No. 0.5 McFarland standard. A
Steers replicator was used to deliver a final inoculum of
105 cfu per spot. The plates were incubated in an anaerobic jar at 36ºC for 48 h. The MIC values were read visual-
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* Department of Dermatology, Faculty of Medicine, University of Chile.
** Department of Dermatology, Faculty of Medicine, University of Los Andes.
*** Program of Microbiology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile.
**** National Health Institute of Chile.
Received January 6, 2006; received in revised form March 1, 2006; accepted April 1, 2006
Gübelin et al
Antimicrobial susceptibility of strains of Propionibacterium acnes
15
Rev Latinoam Microbiol 2006; 48 (1): 14-16
ly as the lowest concentration of the antimicrobial
:rop odarobaleagent
FDP
that prevented visible growth. Control strains included
Bacteroides fragilis ATCC
VC ed25285
AS, cidemihparG
and Eubacterium lentum ATCC 43055.
The antimicrobial susceptibilities of 53
arap
isolates of P.
acnes to 8 antibiotics is shown in Table 1. In the present
study, whichacidémoiB
is the firstarutaretiL
to report of
:cihpargideM
data on the antimicrobial susceptibility of P. acnes in Chile, all of the isolates
sustraídode-m.e.d.i.g.r.a.p.h.i.c
were susceptible to penicillin, minocycline, and nadifloxacin. Two (3.8%) strains were resistant to erythromycin,
and one (1.9%) to clindamycin. One isolate was resistant
to lymecycline, and intermediate to tetracycline and doxycycline.
P. acnes is naturally susceptible to various antimicrobial classes including, β-lactams, macrolide, lincosamide,
quinolone, tetracycline’s and aminoglycoside. 1,4,7 Furthermore, there are numerous topical and or systemic options available for the treatment of acne, being macrolide
and tetracycline’s usually the first-line antimicrobials1,4,7
Nevertheless, since the 1970s antimicrobial resistance
has gradually accumulated in cutaneus isolates of this organism, especially in European countries, with 51 to
94% of strains showing some antibiotic resistance. 8
Erythromycin resistance is the most common antimicrobial resistance detected in P. acnes, with rates ranging
between 17.1 to 52%.6-8 Furthermore, up 91% of the
macrolide resistant strains present combined resistance
with clindamycin.8 Antimicrobial resistance to tetracyclines is lower than that to macrolides, affecting 0 to 26%
of isolates.7,8 In this study, minocycline was as active in
vitro as tetracycline and doxycycline, but no isolates resistant to minocycline were found. Minocycline has also
been rarely associated with P. acnes resistance in other
studies, but can occasionally lead to potentially serious
adverse effects.4 Lymecycline is a new tetracycline as efTable 1. Susceptibility of 53 strains of Propionibacterium acnes to 8 antimicrobial agents.
Antimicrobial
Agent
MIC50
(mg/l)
MIC90
(mg/l)
Range
(mg/l)
% Susceptible
Penicillin G
Erythromycin
Clindamycin
Lymecycline
Tetracycline
Doxycycline
Minocycline
Nadifloxacin
0.03
0.03
0.03
0.25
0.06
0.06
0.03
0.03
0.03
0.03
0.03
1
0.06
0.06
0.03
0.06
≤ 0.03-2
≤ 0.03-32
≤ 0.03-32
0.06-16
0.03-8
0.06-8
0.03-1
≤ 0.03-0.12
100
96.2
98.1
98.1
98.1
98.1
100
100
sustraídode-m.e.d.i.g.r.a.p.h.i.c
fective
as minocycline for the treatment of moderately secihpargidem
ed which
odabor has been associated with fewer advere
acne, and
verse gastrointestinal and dermatological effects than minocycline. 11
Nadifloxacin is a topical fluorquinolone, which acts
through its bactericidal action as well as by the suppression of neutrophil chemotaxis and superoxide formation.10 In our study, nadifloxacin demonstrated to be highly active in vitro against skin isolates of P. acnes, with
MICs ≤ 0.12 µg/ml. Other study has also noted a good activity of this quinolone against this organism.12 However,
our MIC values were lower than that reported by these authors.12
Several strategies have been proposed to prevent the
development of antibiotic resistance that accompanies antimicrobial treatment of P. acnes.1,4,7 They include restrictions in the overall use of antibiotics, avoiding use of systemic antibiotics, and long term therapies. It is highly
advisable not to use concomitantly topical and systemic
antibiotic therapies, but instead to combine use of oral antibiotics with local retinoids.1,4,7 Last drugs improve the
vascularization and benefits further therapy with their
anti-inflammatory effect.4 Topical antibiotics are not intended as first line therapy, and if used should be prescribed with a topical nonantibiotic medication, for example benzoyl peroxides in alternation with retinoids.4,7
Along with, patients may be sufficiently informed about
the dose, duration and form of administration of the treatment, like also the importance of therapy adherence to prevent the selection of resistant strains may be emphasized.
Considering the antimicrobial pattern of our P. acnes isolates, as well as the pharmacokinetic characteristics of the
drugs, the antibiotics of election for the oral treatment of
acne are in order doxycycline, minocycline, and tetracycline. Lymecycline is a good therapy choice for acne, but
it is not available in our country. Erythromycin is a good
alternative for pregnant women and for patients that does
not respond or that present or display allergy to former antibiotics. We do not recommend the prescription of quinolone for topical nor systemic use. Nevertheless, we have
included them in our study since they are used in some
countries.
In conclusion, our results indicate that most P. acnes
strains isolated in our country remain susceptible to antimicrobial agents commonly used in the treatment of inflammatory acne, as well as to new alternatives.
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ACKNOWLEDGEMENTS
MIC50 and MIC 90, MICs at which 50 and 90% of strains, respectively, are inhibited.
This work was supported by a grant from Skin Med
Ltd., Santiago, Chile, to the Faculty of Medicine University of Chile.
16
Gübelin et al
Antimicrobial susceptibility of strains of Propionibacterium acnes
Rev Latinoam Microbiol 2006; 48 (1): 14-16
MG
9.
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Correspondence to:
M. Angélica Martínez
Suecia 1524 Departamento 403
Santiago, Chile
Phone:(562)9786639-9786296
Fax: (562)7355855
E-mail:[email protected]
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