REVIEW

Hryniewicz and Garbacz, Journal of Medical Microbiology 2017;66:1367–

1373
DOI 10.1099/jmm.0.000585

Borderline oxacillin-resistant Staphylococcus aureus (BORSA) –

a more common problem than expected?
Maria M. Hryniewicz* and Katarzyna Garbacz

Abstract
Borderline oxacillin-resistant Staphylococcus aureus (BORSA) represents a quite poorly understood and inadequately defined
phenotype of methicillin resistance. BORSA strains show low, borderline resistance to penicillinase-resistant penicillins
(PRPs), with oxacillin MICs typically equal to 1–8 µg ml 1, and in contrast to methicillin-resistant S. aureus (MRSA), do not
have an altered penicillin-binding protein, PBP2a, encoded by the mecA or mecC gene. Their resistance is typically associated
with hyperproduction of beta-lactamases or, in some cases, point mutations in PBP genes. BORSA cannot be classified as
either truly methicillin-resistant or truly methicillin-susceptible strains. However, they are frequently misidentified, which
poses an obvious epidemiological and therapeutic threat. BORSA strains are commonly isolated from humans and animals,
and are found both in hospitals and in a community setting. The epidemiology and clinical presentation of BORSA infections
seem to be similar to those for MRSA; these infections are usually more severe than those caused by methicillin-sensitive
S. aureus (MSSA). Treatment of severe infections caused by BORSA may be ineffective, even with larger doses of oxacillin.
The available evidence suggests that BORSA represent a frequently neglected problem, and their emergence in new
environments implies that they need to be monitored and accurately distinguished from MSSA and MRSA.

METHICILLIN RESISTANCE IN first case of methicillin resistance in Staphylococcus was

STAPHYLOCOCCUS AUREUS
Staphylococcus aureus is one of the most common human
pathogens; staphylococcal infections vary in severity, from
mild dermatitis to life-threatening sepsis, endocarditis and
toxic shock syndrome. Beta-lactam antibiotics still remain
the treatment of choice for staphylococcal infections. Peni-
cillin, the first antibiotic from this group, was initially
considered to be a ‘wonder drug’ for all staphylococcal infec-
tions, but it soon became evident that it is no longer effec-
tive. Isolation of the first penicillin-resistant staphylococcal
strain had already been reported 2 years after the market
release of this antibiotic in 1942, and shortly thereafter peni-
cillin-resistant strains also emerged in a community setting.
Since the 1960s, resistance to penicillin has been found in
more than 80 % of all S. aureus isolates [1].
Another milestone was the development of resistance to
methicillin, a penicillin that is not susceptible to the staphy-
lococcal enzymes that hydrolyze the beta-lactam ring. The
reported in the United Kingdom as early as 2 years after
market authorization for this antibiotic [2, 3].
Together with nafcillin, oxacillin and cloxacillin, methicillin
belongs to the penicillinase-resistant penicillins (PRPs), i.e.
antibiotics that are not susceptible to degradation with
staphylococcal beta-lactamases. Resistance to methicillin is
usually associated with the presence of the alternative peni-
cillin-binding proteins, PBP2a or PBP2¢, encoded by the
chromosomal genes mecA or mecC (mecALGA251) [4, 5].
Thw staphylococcal PBPs are transpeptidases that are
involved in the transport of peptide precursors for proteo-
glycans (D-alanyl-D-alanine termini) from the cytoplasm to
the cell membrane [6].
Modified PBP2a has a low affinity to beta-lactams and
therefore takes over the function of other PBPs that have
been inactivated by these antibiotics. Due to the presence
of the new protein, methicillin-resistant S. aureus
(MRSA) strains can normally synthesize peptidoglycans
and cross-link them within the cell wall; as a result, such

Received 5 April 2017; Accepted 22 August 2017

Author affiliation: Department of Oral Microbiology, Medical University of Gdansk, Dębowa 25, 80-204 Gdansk, Poland.
*Correspondence: Maria M. Hryniewicz, mariah@gumed.edu.pl
Keywords: Antibiotic resistance; BORSA; MRSA.
Abbreviations: BORSA, borderline oxacillin-resistant Staphylococcus aureus; CA-MRSA, community-acquired methicillin-resistant Staphylococcus
aureus; CLSI, Clinical and Laboratory Standards Institute; EARSS, European Antimicrobial Resistance Surveillance System; FA-MRSA, farm-associated
methicillin-resistant Staphylococcus aureus; HA-MRSA, hospital-acquired methicillin-resistant Staphylococcus aureus; LA-MRSA, livestock-associated
methicillin-resistant Staphylococcus aureus; MLST, multilocus sequence typing; MODSA, modified Staphylococcus aureus; MRSA, methicillin-resistant
Staphylococcus aureus; MSSA, methicillin-sensitive Staphylococcus aureus; PBP, penicillin binding proteins; PFGE, pulsed-field gel electrophoresis;
PRPs, penicillinase-resistant penicillins; PVL, Panton–Valentine leukocidin; spa, Staphylococcus protein A gene.

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 Hryniewicz and Garbacz, Journal of Medical Microbiology 2017;66:1367–1373
strains are no longer susceptible to beta-lactams and
show resistance to antibiotics from many other groups
[7, 8].
Depending on the proportion of staphylococcal cells with
mutant proteins within a given population, resistance to
methicillin can be homogeneous or heterogeneous; in other
words, the resistant phenotype can be expressed by all bacte-
rial cells or only a fraction thereof. The strains with either a
homogeneous or a heterogenous pattern of methicillin
resistance show clinical resistance to beta-lactam antibiotics
[9, 10].
MRSA are typically isolated in a hospital setting; such hos-
pital-acquired MRSA (HA-MRSA) are believed to spread
primarily via human-to-human transmission [11]. How-
ever, an increase in the incidence of infections caused by
non-nosocomial MRSA, referred to as community-acquired
MRSA (CA-MRSA) has been also observed in the
last decade, especially in nursing homes, healthcare centres,
kindergartens and schools [12, 13]. Importantly, infections
caused by these pathogens are usually more severe because
CA-MRSA can synthesize Panton–Valentine leukocidin
(PVL) [13–15].
Since the isolation of the first methicillin-resistant strain of
S. aureus, we have observed a constant increase in the inci-
dence of MRSA infections, and these pathogens remain the
most important challenge in terms of drug resistance, from
both the clinical and epidemiological perspectives [2, 9, 16].
DEFINITION AND PROPERTIES OF
BORDERLINE OXACILLIN-RESISTANT
S. AUREUS (BORSA)
Apart from the synthesis of modified PBP2a, staphylococcal
resistance to methicillin may be also determined by other
mechanisms. One example is the staphylococcal strains
referred to as borderline oxacillin-resistant S. aureus
(BORSA); they show low, borderline resistance to PRPs and
unlike MRSA do not carry modified PBP2a encoded by the
mecA or mecC gene. BORSA strains cannot be classified
as either methicillin-resistant or methicillin-susceptible;
their resistance, usually less pronounced than the one
determined by PBP2a, results from the involvement of
other, sometimes not completely understood mechanisms
[6, 17, 18].
Initially, BORSA were defined as the strains with an oxacil-
lin MIC of 2 µg ml 1 and full susceptibility to PRPs [19].
However, further studies demonstrated that the oxacillin
MIC for some BORSA strains may be higher (4–16 µg ml 1)
and they are not necessarily susceptible to larger doses of
PRPs in vivo [20].
Borderline oxacillin resistance in S. aureus may be deter-
mined by various biochemical mechanisms. The first docu-
mented underlying mechanism of borderline resistance was
the hyperproduction of beta-lactamase. McDougal and
Thornsberry demonstrated that some S. aureus strains
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synthesize particularly large amounts of this enzyme, which
can degrade penicillin (the most hydrolysis-prone antibiotic
from this group) rapidly, but inactivates other beta-lactams,
including PRPs, slowly [21].
A certain portion of staphylococcal beta-lactamases is
released into the surrounding medium or bound to the bac-
terial surfaces. Most beta-lactamases are encoded by plas-
mid genes, usually those carried by class II plasmids [22].
Most S. aureus strains synthesize inducible beta-lactamases
in the presence of an antibiotic. The rate of synthesis is
strain-specific and depends on growth conditions [1]. Usu-
ally, hospital staphylococcal strains produce larger amounts
of beta-lactamases, releasing 40–60 % of the synthesized
enzyme into the growth medium. The synthesis of beta-
lactamase and its release to the extracellular environment
can be also enhanced by the addition of 5–10 % NaCl [23].
If the resistance of BORSA strains to PRPs results from
hyperproduction of beta-lactamase, it can easily be counter-
balanced with inhibitors of this enzyme, such as clavulanic
acid or sulbactam. This distinguishes BORSA from MRSA
strains, where beta-lactamase inhibitors contribute to a
decrease in the penicillin MIC but do not alter the MIC of
PRPs, even at higher concentrations [21].
However, the addition of a beta-lactamase inhibitor does
not necessarily restore the susceptibility of BORSA strains
to oxacillin. This problem has inter alia been described in
S. aureus isolates from cystic fibrosis patients, in which case
the addition of clavulanic acid to the ampicillin disc did not
alter the size of the growth inhibition zone [24]. In turn,
Skinner et al. isolated a BORSA strain whose susceptibility
to cefotaxime and ceftazidime remained unaltered despite
the addition of clavulanic acid [20]. Although this mecha-
nism of resistance to PRPs has not yet been established, it is
definitely not associated with the hyperproduction of peni-
cillinase. According to the above-mentioned authors, resis-
tance to beta-lactam inhibitors may be associated with the
presence of a modified PBP.
These findings suggest that the hyperproduction of conven-
tional penicillinase is not the only cause of the borderline
resistance. Indeed, other mechanisms have been implicated
as possible determinants of the BORSA phenotype, includ-
ing the synthesis of new, plasmid-encoded beta-lactamases
or the modification of PBP genes resulting from spontane-
ous amino acid substitutions in the transpeptidase domain
[25–27]. These modifications typically involve PBP3 and/or
PBP4, and result from the selective pressure of beta-lactam
antibiotics. BORSA strains that carry such modifications
constitute a particular threat from both the epidemiological
and therapeutic perspectives. To be distinguished from
beta-lactamase-hyperproducing BORSA, they are referred
to as modified S. aureus (MODSA) [28]. Similar to the
MRSA strains, MODSA do not became susceptible to PRPs
after the addition of a beta-lactamase to oxacillin.
Another feature of BORSA strains that may contribute to
their misidentification and resultant therapeutic difficulties,
 Hryniewicz and Garbacz, Journal of Medical Microbiology 2017;66:1367–1373
is a lack of species-specific proteins, such as thermonuclease
or coagulase. Recently, Skinner reported infection caused by
the strain showing borderline resistance to oxacillin and
lacking either thermonuclease or coagulase, i.e. two basic
taxonomic characteristics of S. aureus. Aside from difficul-
ties in the selection of an appropriate antibiotic therapy,
another challenge was identification of the isolate at a spe-
cies level [20].
Lacking the expression of species-specific proteins has
primarily been reported in the case of MRSA; this phenom-
enon may result from the insertion of transposon (Tn917)
or the integration of plasmid genes into the chromosome
[29, 30]. According to Duval-Iflah et al. the loss of
the ability to coagulate plasma may result from lysogenic
conversion with LS1 and LS2 phages [31]. However, the rea-
sons behind this phenomenon in BORSA strains are
not completely understood, and this issue requires further
research.
PREVALENCE AND PATHOGENICITY OF
BORSA STRAINS
The infrequent identification of the BORSA phenotype
seems to be primarily associated with the use of diagnostic
methods aimed at the non-selective isolation of all MRSA-
like strains, without an insight into the exact mechanism of
their resistance. The prevalence of BORSA strains is approx-
imately 5 % on average, but may vary from population to
population (1.4 %–12.5 %) [6, 12, 32]. However, some
authors have reported substantially higher prevalence rates
for BORSA. According to Khorvash et al. MRSA strains
without the mecA gene represented up to 25.5 % of all the
isolates were initially designated as MRSA [33]. In another
study, the prevalence of BORSA was estimated at up to 50 %
of all clinical isolates of S. aureus [24]. Given the limited
information available concerning the MRSA detection
methodologies employed in previously published studies,
some of these strains might in fact display borderline resis-
tance to methicillin [24].
The exact prevalence of BORSA strains is difficult to estab-
lish and has not been determined unequivocally thus far.
The carriage rates of BORSA strains have only been the sub-
ject of a few previously published studies. Nevertheless,
these micro-organisms seem to colonize the nares in asymp-
tomatic healthy subjects. In a study of 500 healthy children,
staphylococcal strains with the BORSA phenotype were iso-
lated from more than 5 % of the subjects [34, 35]. In another
study examining staphylococcal infections in animals, some
isolates turned out to originate from animal keepers who
were asymptomatic carriers of BORSA [36].
BORSA were found in both hospital and community set-
tings. To date, strains with this resistance phenotype have
been isolated from skin and soft tissue infections [32, 37],
surgical wounds [38], airways [24, 33] and the urinary tract
[39]. However, BORSA may be also involved in the etiopa-
thogenesis of some more severe infections, such as
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endocarditis and sepsis [20]. In a hospital setting, BORSA
are most frequently isolated in dermatology units [32, 37,
39].
The symptomatology of BORSA infections seems to be sim-
ilar to that in the case of MRSA; the infections are usually
more severe than those caused by MSSA. In a study con-
ducted by Balslev et al., patients from a dermatology unit
who had been infected with BORSA presented with more
severe symptoms, more often required rehospitalization and
had more bed days than MSSA-infected controls [32].
Owing to similar clinical presentation, infections caused by
BORSA may sometimes be misdiagnosed as MRSA (partic-
ularly CA-MRSA) infections. Similar to CA-MRSA, BORSA
may cause community-acquired soft-tissue infections and
necrotic pneumonia, and their isolation may be associated
with a history of previous antibiotic therapy [40–42].
Many researchers point to the administration of antibiotics
as the main risk factor for developing the BORSA
resistance phenotype. In one study, patients with cystic
fibrosis who had previously been treated with oral cepha-
lexin and inhaled tobramycin due to MSSA infections,
turned out to be particularly prone to colonization with
BORSA. According to the authors of this study, BORSA
strains might develop due to selective antibiotic pressure, as
a variant of methicillin-resistant strains [24]. Indeed,
BORSA isolates from cystic fibrosis patients showed a low
degree of strain relatedness and presented with variable
PFGE patterns. This implies that they were unlikely to have
been transmitted from patient to patient, but rather evolved
from strains that had previously acquired methicillin resis-
tance [24].
On the other hand, some evidence suggests that BORSA
may spread from patient to patient. Studies involving vari-
ous genotyping methods (PFGE, MLST and spa typing)
demonstrated a high degree of strain relatedness in BORSA
isolates. In a study conducted by Thomsen et al., up to 93 %
of the BORSA strains found in a dermatology unit repre-
sented the same spa type, t230 [37]. According to
the authors of this study, the fact that only one clone had
been spread selectively across the unit might have been the
result of prolonged preferential use of beta-lactams (dicloxa-
cillin) and direct patient-to-patient contacts [37]. In line
with these findings, Nadarajah et al. demonstrated that
most BORSA isolates showed the same PFGE A pattern,
corresponding to the ST25 lineage, which was not related to
any of the five clonal complexes found in MRSA [43]. Simi-
larly, more than 80 % of the BORSA isolates from equine
wound infections represented the same clonal complex, ST-
1/t2863, which probably emerged as a result of the routine
preoperative prophylactic administration of penicillin [36].
PREVALENCE OF BORSA IN ANIMALS
The prevalence of staphylococci with borderline resistance
to oxacillin is not limited solely to the human population.
BORSA have been also isolated from cattle, horses and
 Hryniewicz and Garbacz, Journal of Medical Microbiology 2017;66:1367–1373
poultry, as well as other livestock [36, 44–47]. The preva-
lence and genotype of animal BORSA isolates vary depend-
ing on geographic latitude, host species and breeding
system. In one study, up to 14 % of S. aureus isolates from
the nasal cavity of pigs kept at two farms showed borderline
resistance to oxacillin [46]. The evaluation of staphylococcal
infections occurring in horses treated at a Swiss clinic docu-
mented even an higher (more than 25 %) contribution of
BORSA strains [36]. Importantly, most equine infections
recorded at this clinic were caused by one predominant
clone. Staphylococci with borderline resistance to oxacillin
might also contribute to a certain proportion of infections
in poultry (chickens and turkeys) [45].
BORSA were also isolated from foods. A number of previ-
ous studies demonstrated the presence of this pathogen in
ruminant milk, and a few authors have isolated BORSA
strains from animal meat. The carriage of BORSA among
livestock was shown to be linked with the further isolation
of these strains from animal products. The isolation of
BORSA from foods was first reported in 2010 [48].
However, the origin of the borderline resistant strains found
in foods is still unclear. Presumably they originate from two
sources. Isolates from some products that have been proc-
essed by humans, such as minced pork and ruminant milk,
showed genetic relatedness to strains isolated from food
industry workers [24, 49]. However, the carriage of BORSA
among livestock may also contribute to the presence of
these strains in foods of animal origin [46]. Consequently,
both humans and animals may constitute a source of infec-
tion and contribute to the contamination of food with
BORSA.
Presumably, as in MRSA, one reason for the emergence of
BORSA in the animal population and foods is the wide-
spread use of antibiotics. A growing body of evidence
is documenting the presence of MRSA strains in livestock
and the possibility of their transmission to humans, as live-
stock-associated MRSA (LA-MRSA) or farm-associated
MRSA (FA-MRSA) [50–54]. The selection of these multi-
drug-resistant staphylococci is undoubtedly promoted by
the widespread use of antibiotics as a component of animal
fodder. For example, nearly 80 % of all antibiotics consumed
in the United States are used for animal feeding purposes
[55]. According to Casey et al., livestock operations requir-
ing frequent contact with pigs are associated with 38 and
30 % greater risk of CA-MRSA and HA-MRSA infection,
respectively. To the best of our knowledge, no equally accu-
rate data regarding the risk of infection with BORSA strains
have been published thus far.
DETECTION OF BORSA STRAINS
The detection of BORSA in clinical material is a prerequisite
for effective antibiotic therapy. Unfortunately, BORSA
detection methods that can be used in routine diagnostics
remain to be developed. Due to the lack of such methods,
some BORSA strains may be misdiagnosed as MRSA or
MSSA isolates.
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The risk of the misdiagnosis is undoubtedly associated with
the use of routine protocols to detect methicillin resistance.
In line with the recommendations of the European Antimi-
crobial Resistance Surveillance System (EARSS), since 2005
cloxacillin discs (1 µg) have been replaced by cefoxitin discs
(30 µg). An S. aureus isolate is considered to be resistant if
the inhibition zone around the cefoxitin disc is no greater
than 21 mm. According to the Clinical and Laboratory
Standards Institute (CLSI) guidelines from 2009, the strain
is classified as MRSA whenever its oxacillin MIC amounts
to 8 µg ml 1 [56].
Susceptibility to cefoxitin is also a good marker of staphylo-
coccal sensitivity to PRPs and other beta-lactams. Unfortu-
nately, this parameter cannot be considered as a marker of
borderline methicillin resistance if the latter involves
a different mechanism than the presence of PBP2a (mecA/C
gene). BORSA strains are identified as methicillin-sensitive
and methicillin-resistant based on the size of the inhibition
zone around cefoxitin (30 µg) and oxacillin (1 µg) disc,
respectively [39]. If only susceptibility to cefoxitin is tested,
a BORSA strain may be misidentified as an MSSA isolate.
Therefore, it is recommended that both cefoxitin and oxacil-
lin susceptibility be tested for the detection of BORSA in a
laboratory setting [39, 57, 58].
In most S. aureus strains, borderline resistance to oxacillin
is determined by the hyperproduction of beta-lactamases
[24, 45, 46]. The involvement of this mechanism is typically
confirmed by a cefinase test with a nitrocefin disc.
Alternatively, the bactericidal/bacteriostatic activity of a
beta-lactamase inhibitor, e.g. clavulanic acid, in combina-
tion with a PRP can be determined. BORSA strains become
fully susceptible to oxacillin in the presence of a beta-lacta-
mase inhibitor [59] and, consequently, both their MIC and
the size of the inhibition zone have values that are typical
for a sensitive strain. However, both of these parameters
remain unchanged in the case of either methicillin-sensitive
or methicillin-resistant strains [20].
Sometimes distinguishing between BORSA and MRSA
strains may be challenging due to overlapping oxacillin
MICs [12]. In line with the CLSI guidelines, a strain can be
classified as MRSA if its oxacillin MIC is equal to 8 µg ml 1
or higher [56]. However, some MRSA may have oxacillin
MICs below 8 µg ml 1, and MICs for some BORSA isolates
may exceed this cut-off value [20, 24]. Published evidence
suggests that in such cases, qualification of a strain as
BORSA/MRSA should be based on determination of PBP2a
with latex agglutination and/or detection of mecA and mecC
genes by means of PCR. In the case of BORSA strains, both
these tests produce negative results [60, 61].
According to the literature, unlike CA-MRSA isolates,
BORSA strains lack the PVL locus responsible for
the expression of the Panton–Valentine toxin [26]. How-
ever, the data available for this matter are still sparse.
Selective chromogenic media are increasingly being used
for the one-step isolation and identification of MRSA.
 Hryniewicz and Garbacz, Journal of Medical Microbiology 2017;66:1367–1373
The growing popularity of such media is associated with the
need for the rapid detection and identification of CA-MRSA
and HA-MRSA. Early detection is crucial for adequate con-
trol of their spread, and improves the effectiveness of treat-
ment while shortening its duration. However, the growing
popularity of chromogenic media has stimulated questions
about their sensitivity and specificity in distinguishing
between various phenotypes of methicillin resistance in S.
aureus, including BORSA.
A recent study included four chromogenic media for
the detection of MRSA – MRSA Select II (BioRad, USA),
Colorex MRSA (E&O Laboratories, UK), ChromID MRSA
(bioMerieux, France) and MRSA Brilliance 2 (Oxoid, UK)
– and confirmed their high (nearly 100 %) sensitivity but
markedly lower specificity [62]. The reduced specificity of
the chromogenic agars was demonstrated by the high recov-
ery of BORSA, with almost 50 % false positive results on all
four media. The authors of this study linked this result to
the high values of oxacillin MIC (4–8 µg ml 1) for the ana-
lysed BORSA strains. Misdiagnosis of BORSA as MRSA
undoubtedly has a negative impact on the control of their
spread in hospitals and in a community setting. This implies
that strains showing borderline resistance to PRPs should
be identified with other, more accurate methods than the
chromogenic media.
Another unquestioned obstacle to the accurate identifica-
tion of BORSA isolates is the previously mentioned lack of
species-specific factors, such as coagulase and thermonu-
clease [20].
PROBLEMS WITH TREATMENT OF BORSA
INFECTIONS
The detection of S. aureus strains with borderline resistance
to oxacillin in a clinical material may hinder the selection of
an appropriate antibiotic therapy [12, 20]. Initially, infec-
tions caused by BORSA with oxacillin MICs 2 µg ml 1
were treated with PRPs. BORSA strains were often not con-
sidered to be resistant to beta-lactams, despite synthesizing
large amounts of beta-lactamases that slowly hydrolyzed
these antibiotics in vitro. However, the process of hydrolysis
was considered to be too slow to have any meaningful clini-
cal implications, such as treatment failure [18, 27].
However, this concept evolved with time. Currently, mecA-
negative S. aureus strains with higher oxacillin MICs (4 µg
ml 1) are considered to be a therapeutic challenge, and oxa-
cillin and other PRPs, even at higher doses, are known to be
inefficient in the treatment of severe BORSA infections.
This was unequivocally considered to be the case by Skinner
et al. in 2009. The oxacillin MIC for the strain isolated from
a patient with endocarditis was 12 µg ml 1 (E-test) and the
results of testing for mecA and BPP2a were negative. Fur-
thermore, the nitrocefin test showed that the isolate did not
produce beta-lactamases, which was further confirmed by
the lack of a significant increase in the growth inhibition
zones around cefotaxime–clavulanic acid and ceftazidime–
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clavulanic acid discs. While the exact mechanism of oxacil-
lin resistance in this case has not been identified, it
undoubtedly did not involve the hyperproduction of peni-
cillinase. After identification of the aetiological factor as
BORSA, the patient was switched from oxacillin to vanco-
mycin, which eventually resulted in therapeutic success
[20].
However, this does not mean that BORSA infections cannot
be treated with beta-lactams. The treatment of choice in
such cases still comprises large doses of penicillinase-resis-
tant penicillins (e.g. cloxacillin) or beta-lactams +beta lacta-
amase inhibitors (e.g. ampicillin/sulbactam), providing
earlier determination of their MICs and adequate assess-
ment of symptom severity [12, 63, 64]. Beta-lactams should
only be implemented after a substantial decrease in MIC (by
at least twofold) or a 5 mm increase in growth inhibition
zone around the disc with beta-lactamase inhibitor have
been confirmed [20].
A key issue that needs to be determined prior to the
implementation of an anti-staphylococcal treatment is dis-
tinguishing between BORSA and MRSA. Without differen-
tiating between these two phenotypes of antibiotic
resistance, each infection should be treated as MRSA, i.e.
with other antibiotics than beta-lactams, e.g. vancomycin.
As is widely known, such an approach is not beneficial in
patients with severe staphylococcal infections, such as
endocarditis or sepsis, where vancomycin has been shown
to be inferior to beta-lactams. Whenever the absence of
the mecA gene is confirmed with an appropriate test, the
patient should be diagnosed for BORSA infection; in such
cases, beta-lactams may be considered to be a therapeutic
option after the oxacillin MIC, synthesis of beta-lacta-
mases or lack thereof and clinical presentation have been
taken into account [12, 24].
Isolates with the BORSA phenotype may be multidrug-
resistant, i.e. show resistance to at least three antibiotics
from various groups. According to the literature, BORSA
may show resistance to aminoglycosides, including genta-
mycin/kanamycin, which is determined by the (acc(6¢)-Ie-
ph(2¢)-Ia) gene, streptomycin (str gene) and trimethoprim
[dfr (A) gene] [36]. Furthermore, BORSA may show (usu-
ally inducible) resistance to macrolides and lincosamides
[12, 45, 46].
Funding information
The authors received no specific grant from any funding agency.
Conflicts of interest
The authors declare that there are no conflicts of interest.
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