Antimicrobial resistance profile of methicillin resistant staphylococcal aureus from skin and soft tissue isolates
Antimicrobial resistance profile of methicillin
resistant staphylococcal aureus from skin and soft
tissue isolatesFaiza IdreesAga Khan University
Kauser JabeenAga Khan University
Muhammad Shoaib KhanAga Khan University
Afia ZafarAga Khan University
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Idrees, F., Jabeen, K., Khan, M., Zafar, A. (2009). Antimicrobial resistance profile of methicillin resistant staphylococcal aureus from
skin and soft tissue isolates. Journal of the Pakistan Medical Association, 59
(5), 266-9.Available at:
Antimicrobial resistance profile of Methicil in Resistant Staphylococcal
Aureus from skin and soft tissue isolates
Faiza Idrees, Kauser Jabeen, Muhammad Shoaib Khan, Afia Zafar
Department of Pathology & Microbiology, Aga Khan University Hospital, Karachi, Pakistan.
To evaluate resistance rates in methicillin resistant Staphylococcus aureus (MRSA) against
clindamycin, cotrimoxazole, tetracycline, fusidic acid, rifampicin and chloramphenicol isolated from skin and soft
tissue infections (SSTI).Methods:
Descriptive analysis of SSTI samples yielding MRSA in clinical laboratory of a tertiary care center;
receiving specimens across Pakistan from January 2005 to June 2007.Microbiological Methods:
MRSA were identified using standard microbiological techniques. Susceptibility
testing was performed by disc diffusion according to Clinical Laboratory Standards Institute (CLSI) against fusidic
acid, tetracycline, cotrimoxazole, clindamycin, rifampicin and chloramphenicol. Minimum inhibitory
concentrations (MIC) of rifampicin were determined using agar dilution method according to CLSI. Results:
During the study period 501 MRSA were isolated from SSTI. Overall variable susceptibility pattern with
high resistance rates to tetracycline (82%), clindamycin (79%), cotrimoxazole (59%), and rifampicin (50%) were
observed. Resistance to chloramphenicol (10%) and fusidic acid (9%) was low. Conclusion:
There is a strong need in resource limited countries to review the utility of conventional antibiotics
for the management of MRSA SSTI as new agents are expensive and not available. High resistance rates were
observed against cotrimoxazole, tetracycline and clindamycin. Resistance to fusidic acid, rifampicin and
Chloramphenicol was low (JPMA 59:266; 2009).
requires hospitalization.3 Final y, it is a nephrotoxic drug and
Staphylococcus aureus causes skin and soft-tissue
requires monitoring of renal function and drug levels that lead
infections (SSTIs) that range from fol iculitis to life-
to increased morbidity and costs for the patient.
threatening conditions, such as necrotizing fasci tis.1
Alternate options for the MRSA infections include
Emerging methicil in resistance among Staphylococcus
newer agents like linezolid, daptomycin, tigecycline, and
aureus initial y in nosocomial and recently in community
quinupristin/dalfopristin.3 However, these agents are either
isolates is problematic because empirical choice of
very expensive or not available in Pakistan.3 Guidelines for
antimicrobials must include agents with activity against
the treatment of skin and soft tissue infections published by
resistant strains.2 Management of MRSA infections is
CDC in 2005 have also recommended the use of macrolides,
chal enging as these strains are resistant to al beta lactam
antibiotics. In contrast to health care associated MRSA
doxycycline or minocycline in minor MRSA infections.4
isolates that are resistant to multiple antibiotics, community-
In addition, many studies from different regions of
associated MRSA isolates tend to be resistant to fewer
the world have reported efficacy of fusidic acid, rifampicin,
antibiotics and often remain susceptible to non-beta lactam
antibiotics, such as clindamycin, sulfonamides, and
chloramphenicol in skin and soft tissue infections with
MRSA.5,6 All of these antibiotics are potent
Vancomycin has excel ent efficacy in skin and soft-
antistaphylococcal agents with good tissue penetration,
tissue infections in general and specifical y against those due
cheaper as compared to glycopeptides and are also available
to MRSA.3 However, for various reasons these agents should
in both oral and parenteral formulations.4 However, their use
be reserved for patients who have severe infections requiring
is limited in developed countries due to their potential
hospitalization or who have not responded to at empts to
eradicate the infection. Firstly, excessive use of vancomycin
There is a strong need in resource limited countries
would result in emergence of vancomycin resistance.2,3
like Pakistan to review the utility of conventional antibiotics
Secondly, vancomycin is expensive and available only in
effective for the management of skin and soft tissue infections
parenteral form and most of the times its administration
caused by MRSA. However, published data in Pakistan is
limited in this regard. Therefore, this study was conducted to
explore the cheaper and easy to administer drugs for soft tissue
infections by MRSA. The susceptibility pat ern of MRSA
strains were evaluated against fusidic acid, cotrimoxazole,
rifampicin, chloramphenicol, clindamycin and tetracycline
isolated from SSTIs. Moreover, studies from Pakistan that
reported susceptibility pat ern of MRSA were reviewed and
their findings were correlated with our results.
Material and Methods
This study was conducted at the Clinical Microbiology
Laboratory of Aga Khan University Hospital that receives
specimens from across Pakistan via its col ection points. Skin
(FD= Fusidic acid, 10µg; C=Chloramphenicol, 25µg; R=Rifampicin; TE= Tetracycline,
and soft tissue samples yielding growth of S.aureus from
30µg; SXT= Cotrimoxazole, 30µg; DA= Clindamycin, 2µg)
January 2005 to June 2007 were included. Organisms were
Figure: Resistance pattern of MRSA.
identified as S.aureus by Gram stain, catalase and coagulase
test.7 Other supplemental tests were DNAse, phosphatase and
chloramphenicol (C) (10%) and fusidic acid (FA) (9%) was
mannitol fermentation.7 Antimicrobial sensitivities against
oxacil in (1 g), fusidic acid (10 g), cotrimoxazole (30µg),
Analysis of data from the studies done in various
tetracycline (30µg), clindamycin (2µg) and chloramphenicol
regions of Pakistan is shown in Table.
(25 µg) were performed by Kirby Bauer method according to
Clinical Laboratory Standards Institute (CLSI).8 Methicil in
resistance was confirmed by oxacil in screen agar containing
Increasing antimicrobial resistance has emerged
6 g/ml oxacil in and incubation at 30 C for 24 hours.8
globally as one of the paramount microbial threats of the
Sensitivities against rifampicin were determined by minimum
21st century.9 Infections due to MRSA are the significant
inhibitory concentration (MIC) method using agar dilution
cause of morbidity and mortality worldwide. Incidence of
according to CLSI.8
MRSA is increasing worldwide, and is escalating in
Literature review was done using Pubmed, google,
Pakistan.10-13 Previously MRSA infections were a concern
medscape and Pakmedinet using different terms "MRSA and
only in hospitals but now MRSA is isolated frequently from
susceptibility pat ern", "MRSA and skin and soft tissue" etc.
the infections acquired in the community.14 Skin and soft
Al the information was recorded on a standard questionnaire.
tissue infections are the major manifestations of
community-acquired MRSA strains. During the past 15
years emergence and dissemination of these strains had led
During the study period a total of 501 MRSA strains
to major therapeutic and infection control related problems.
were isolated from skin and soft tissue specimens. Overall,
Methicil in resistance in Staphylococcus aureus
variable susceptibility pat ern was observed in MRSA
restricts therapeutic options for clinical isolates; especially
strains, with high resistance rates to tetracycline (TE)
those isolated from SSTIs. Alternative treatment options
(82%), clindamycin (DA) (79%), cotrimoxazole (SXT)
include fusidic acid, cotrimoxazole, clindamycin,
(59%), and rifampicin (R) (50%). Resistance to
tetracycline, rifampicin, quinolones, and chloramphenicol.
Table: Percentage resistance in MRSA isolates reported in various studies from Pakistan.
No. of MRSA Isolates
Emerg Infect Dis24
J Pak Med Assoc25
Vol. 59, No. 5, May 2009
Prediction of sensitivity to these drugs requires knowledge
infection is yet to be defined. There are certain trials of
of antibiotic susceptibility pattern of MRSA from a
usage of chloramphenicol in multi-drug resistant gram-
particular region. Our MRSA strains from both hospital and
positive organisms like MRSA, vancomycin-intermediate
community showed low resistance to fusidic acid that is
comparable with studies reported from USA,9,14 Australia5
Staphylococcal.aureus (VRSA) and vancomycin-resistant
and South Africa.15 Fusidic acid is available in intravenous,
enterococcus (VRE).20 Chloramphenicol is routinely used
oral, and topical preparations and when given systemically
for the management of VRE infections at our institute. Data
is widely distributed throughout the body, including areas
for use of this antibiotic for the management of MRSA
such as bone, joint fluid, prostate and large abscesses.16
infections is limited; however, it should be reserved for
Therefore, it can be particularly useful in treating MRSA.16
cases when there are very limited therapeutic options.
However, it is well recognized that use of fusidic acid, as
Further clinical trials are needed before its routine use is
monotherapy, is associated with increased resistance as
indicated for the treatment of MRSA infections.
compared to combination therapy.16 Therefore, combination
In this study, all the strains showed susceptibility to
treatment with rifampicin or cotrimoxazole is advisable and
vancomycin. Vancomycin is a glycopeptide and is currently
proven to be beneficial in treatment and eradication of
a drug of choice for MRSA infections.4 Since there is
MRSA stains.5,9 Recent studies from different parts of the
recognition of VRE, the emergence of VRSA has been
world indicate increase in the usage of fusidic acid as
anticipated in future. There are few reports of VRSA/VISA
topical monotherapy for the treatment of skin infections
cases from US.21 One of the common risk factor for
especially in Europe.17 Such topical therapy has proven
acquiring VISA is the long-term use of vancomycin.22 It is
effective but has also been associated with significant
therefore important to consider alternate treatment options
emergence of resistance.17 Thus, clinicians should
for MRSA infections to prevent the VISA/VRSA
reconsider the use of topical fusidic acid monotherapy
especially for prolonged periods.
acquisition. The emergence of S.aureus with reduced
susceptibility to Vancomycin presents the potential for
The resistance to rifampicin (50%) was relatively
infection with a virulent organism for which therapeutic
better as compared to other agents. Rifampicin is another
options are severely limited.
oral antimicrobial agent with good tissue penetration. This
agent could be used to treat MRSA infections in our setting.
Comparison of our study results with other
However, as Pakistan is a high burden Mycobacterium
published studies of Pakistan from Lahore,23 Rawalpindi24
tuberculosis (TB) country, increased usage of rifampicin is
and Karachi25 revealed resistance rates against clindamycin,
not advisable as a routine for the management of MRSA
tetracycline and cotrimoxazole similar to our study.
SSTI because of potential development of resistance in TB.
Likewise, rifampicin sensitivity results and fusidate
However, its use is justified in certain difficult clinical
sensitivity from a previous study done in Karachi25
situations when treatment options are very limited.
correlated with our findings.
We observed high resistance rates to clindamycin,
tetracycline and cotrimoxazole in our MRSA isolates. A
MRSA is a major pathogen in skin and soft tissue
higher rate of clindamycin resistance in endemic isolates is
infections worldwide. One of the limitations of this study is
disappointing as this drug has a very good efficacy in
the lack of differentiation between hospital acquired and
community associated strains. Therefore, no comments can
Cotrimoxazole has also been used in clinical studies
be made on the difference in susceptibility pattern of
with a cure rate of 86-90% in MRSA SSTI18 Likewise,
community and hospital acquired strains. High resistance
tetracycline derivatives, doxycycline and minocycline also
rates against cotrimoxazole, tetracycline and clindamycin
have excellent tissue penetration, and demonstrate good
were observed. Therefore, empirical therapy with these
antistaphylococcal activity at clinically achievable levels
agents at our centre is not recommended; however, these
with a reported cure rate of 83% in MRSA skin and soft
agents could be used after the sensitivity results are
tissue infections.19 However, high resistance rates to this
available. Resistance to fusidic acid and rifampicin was
drug were observed in our study probably due to irrational
low; however, as monotherapy with these agents could lead
use of this antibiotic by general practitioners in Pakistan.
to resistance, therefore, combination therapy should always
Another concern is the toxicity that is associated with
be used. Resistance to chloramphenicol was very low but
clinical trials recommending its use in MRSA skin and soft
Resistance to chloramphenicol was low (10%);
tissue infections are limited and further evidence is required
however, its role in management of MRSA soft tissue
before its routine use.
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Vol. 59, No. 5, May 2009
DORAMECTINA 1,1%. Endectocida altamente efectivo para el control y tratamiento de los parásitos internos y externos. NOVIEMBRE DE 2013 Doramectina es una lactona macrocíclica Figura 1. Origen y clasificación de las lactonas semisintética, perteneciente a la familia de macrocíclicas: avermectinas y milbemicinas (tomado de Lifschitz y col 2002).
Target cell availability and the successful suppression of HIV by hydroxyurea and didanosine Rob J. De Boer AIDS 1998, 12:1567–1570 Keywords: Hydroxyurea, immunosuppression, target cell availability, 72 weeks of ddI–HU treatment, three out of sixpatients had no detectable plasma virus, and that there