The Widening Challenge: How to Learning

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The Widening
Challenge:
How to
Manage
MRSA
This once-limited
organism is now
thriving outside
the hospital.
Learning
Objectives
Upon completion of
this article, the reader will
1) Have an appreciation
for the increasing prevalence of communityacquired and hospitalacquired MRSA.
2) Be able to identify community-acquired and hospital-acquired MRSA on a culture and sensitivity report.
3) Have a basic understanding of the mechanism of resistance and
the rationale for antibiotic selection for MRSA.
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Photodisc
By Warren S. Joseph, DPM and Mark
Kosinski, DPM
S
taphylococcus aureus is one
of the most common organisms encounteredin podiatric
practice. For decades, beta-lactam
www.podiatrym.com
antibiotics have been the mainstay
of therapy. Unfortunately, this
treatment paradigm is changing.
Staphylococcus Aureus, an
Evolving Pathogen
Staphylococcus aureus is one of
the most common organisms encountered in podiatric practice. For
decades, beta-lactam antibiotics have
been the mainstay of therapy. Unfortunately, this treatment paradigm is
changing. Methicillin-resistant
Continued on page 140
NOVEMBER/DECEMBER 2005 • PODIATRY MANAGEMENT
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MRSA...
Staphylococcus aureus (MRSA)
has been isolated with increasing
frequency from lower extremity infections. In some settings, MRSA has become the predominant form of S.aureus isolated from uncomplicated skin
infections in the community. Some
strains of MRSA produce cytotoxic virulence factors, resulting in severe
necrotizing infections. In the era of resistance, the importance of taking a
culture has taken on new meaning.
MRSA: Thriving Outside the
Hospital
Since the introduction of penicillin in 1941, S. aureus has undergone a slow but steady metamorphosis. Methicillin was first introduced for clinical use in 1960 to
combat the growing incidence of
beta-lactamase production among
S. aureus. Within a year of its introduction, the first strains of S. aureus
resistant to methicillin began to
emerge in the United Kingdom.
Shortly afterwards, in 1963, MRSA
appeared among staphylococci
causing blood stream infections in
Danish hospitals. Originally a nosocomial pathogen, MRSA has become endemic in the United States
and many parts of the world and
has become increasingly common
in the community, occurring in patients with and without established
risk factors.
Mechanism of Resistance
To understand why some drugs
are active against MRSA and others are not, it is helpful to look at
Since the
introduction of
penicillin in 1941,
S. aureus has
undergone a slow
but steady
metamorphosis.
the mechanism of resistance. Methicillin resistance is associated
with the presence of penicillin
binding protein 2a (PBP2a).
PBP2a, encoded by the mec A
gene, has a low affinity for Betalactam antibiotics, resulting in resistance to all currently available
Beta-lactam drugs. By definition,
penicillins, cephalosporins, carbapenems and monobactams have
no activity against MRSA. Horizontal transfer of the mec A gene
Why is oxacillin tested instead
of methicillin?
A useful drug in its day, methicillin has fallen out of use in favor
of safer, more active antibiotics.
When reviewing a culture and sensitivity report, we now look to
oxacillin as a surrogate marker for
methicillin resistance. Oxacillin is
more resistant to degradation in
storage and is more likely to detect
heteroresistant strains than methicillin. The acronym MRSA is still
used to describe these isolates because of its historic role. For all
practical purposes, resistance to
oxacillin (ORSA) is synonymous
with resistance to methicillin
(MRSA). MRSA is defined as having
an oxacillin MIC90>/= 4ug/ml.
All MRSA is Not Created Equal
MRSA can be divided into two
main types: community-acquired
MRSA (CA-MRSA) and hospital-acquired MRSA (HA-MRSA). The distinction between the two has become
more difficult over the years as HAMRSA strains move into the community and CA-MRSA strains move into
the hospital. Each, however, has important distinguishing features.
Continued on page 141
FIGURE 1
FIGURE 2
Community-acquired
MRSA (CA-MRSA)
Hospital-acquired MRSA
(HA-MRSA)
Antibiotic
Sensitivity
Antibiotic
Sensitivity
Cefazolin
Amoxicillin
Oxacillin
Erythromycin
Tetracycline
Clindamycin
TMP/SMX
Vancomycin
Linezolid
Resistant
Resistant
Resistant
Resistant
Sensitive
Sensitive
Sensitive
Sensitive
Sensitive
Cefazolin
Amoxicillin
Oxacillin
Erythromycin
Tetracycline
Clindamycin
TMP/SMX
Vancomycin
Linezolid
Resistant
Resistant
Resistant
Resistant
Resistant
Resistant
Resistant
Sensitive
Sensitive
Multi-drug susceptible, community-acquired MRSA. Note
susceptibility to all beta-lactam antibiotics.
140
into known MSSA strains converts
the strains into MRSA in all cases.
Multi-drug resistant, hospital-acquired MRSA.
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MRSA...
beta-lactam antibiotics. This explains why HA-MRSA strains are
multi-drug resistant. Type II is the
most prevalent of these HA-MRSA
strains found in the United States.
SCC mec elements IV and V
found in CA-MRSA strains lack an-
tential to be more tissue
destructive than its hospital counterpart. This is in part
due to the production of cytotoxic virulence factors known as
Panton Valentine Leukocidins
(PVL’s). CA-MRSA isolates containing PVL genes have been
linked to recurrent, severe necrotizing skin infections similar to those
seen in Group A Streptococcal disease2. PVL’s create pores in the leukoCA-MRSA
cyte membrane causing
cell death and are
Type IV, V
thought to be in part responsible for the rapid
More
spread of infection. PVL
More Common
genes are less commonly
found in HA-MRSA or
Sensitive except
MSSA community isoBeta-lactams
lates.
Strict definitions for CA-MRSA
vary. The Centers for Disease
Control and Prevention have defined CA-MRSA as an isolate obtained from a patient in an outpatient setting or in the
first 48 hours of hospitalization in the absence of identified risk
factors for acquisition.
Others have relied on
the antibiotic resistance
Feature
HA-MRSA
profile, usually referring
to clindamycin suscepMec-A
Type I, II,II
tibility to define CAMRSA isolates1.
Toxins
Fewer
What all strains of
PVL
Rare
MRSA have in common
is the presence of the
Abx Resistant
Multiply
mec-A gene and resisresistant
tance to all antibiotics
containing a Beta-lactam
Inducible Clindamycin
ring. Where CA-MRSA
Community-acquired MRSA produce more toxins and virulence
Resistance: MLS
and HA-MRSA differ is in
factors than its hospital counterpart.
Clindamycin contintheir susceptibility to
ues to be a commonly-prescribed
non-beta lactam antibiotics. CAtibiotic resistance genes other than
antibiotic for the treatment of meMRSA can be considered multi-drug
mecA, thereby explaining resisthicillin-susceptible Staphylococcal
susceptible (Figure 1), whereas HAtance only toward beta-lactam
infections, and has even shown to
MRSA can be considered multi-drug
drugs. CA-MRSA can be considhave activity against some strains
resistant (Figure 2). The reason for
ered, by comparison, to be a multiof CA-MRSA. It is likely, however,
this apparent paradox lies in their
drug susceptible type of MRSA.
that the true incidence of clingenetic makeup.
damycin resistance has been underThe mec-A gene is contained
CA-MRSA: Multi-Drug
estimated.
within a mobile genetic element
Susceptible, But More Virulent
It is standard practice to rely on
called the staphylococcal chromoAlthough originally thought to
some cassette mec or SCCmec.
be a less virulent organism, MRSA
Continued on page 142
has recently been
shown to be
more virulent
MRSA can be
than MSSA. In a
study by Engedivided into two
mann in 2003,
main types:
patients
with
MRSA skin and
community-acquired
skin structure inAntibiotic
Sensitivity
MRSA (CA-MRSA)
fections had a
Ampicillin-sulbactam
Resistant
greater 90-day
and hospital-acquired
mortality,
a
Cefazolin
Resistant
MRSA (HA-MRSA).
longer duration
Penicillin
Resistant
of infection and
incurred twice
Oxacillin
Resistant
the amount of
There are currently five known alErythromycin
Resistant
hospital charges
lotypes, designated SCCmec types
Clindamycin
Sensitive
versus those paI-IV. HA-MRSA strains contain SCtients with MSSA
Cmec types I, II and III. Whereas
Tetracycline
Sensitive
infections5.
CA-MRSA strains contain SCC mec
TMP/SMX
Sensitive
types IV and V (Figure 3).
Paradoxically,
Vancomycin
Sensitive
The genetic sequence of type
although more
SCCmec found in HA-MRSA resusceptible to anveals plasmids and transposons
tibiotics,
CAthat mediate resistance to nonMRSA has the po- CA-MRSA with Inducible Clindamycin Resistance
FIGURE 3
MRSA Differences
FIGURE 4
Inducible Clindamycin
Resistance
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MRSA...
a culture and sensitivity report to choose an antibiotic for
directed therapy. In the case of
clindamycin, however, culture and
sensitivity results may not always
be reliable. A phenomenon known
as inducible clindamycin resistance (ICR) may mislead the clinician into thinking that a particular
strain of S. aureus is susceptible to
clindamycin, when in fact it is not.
During laboratory testing, S. aureus appears to be resistant to erythromycin and susceptible to clindamycin, however, once the patient is exposed to clindamycin, he
or she may quickly develop resis-
Although
originally thought
to be a less virulent
organism, MRSA has
recently been shown to
be more virulent
than MSSA.
tance (Figure 4).
Staphylococcal strains which possess the erm gene prevent macrolides
and lincosamides (erythromycin and
clindamycin) from binding to their
target site. Clindamycin is a poor inducer of the erm gene compared to
erythromycin. The isolate may appear sensitive on laboratory testing
but the patient may fail to respond
clinically. Inducible clindamycin resistance is seen in both MRSA and
MSSA isolates. It has also been found
that this inducible resistance extends
to streptogramin b antibiotics, giving
rise to the acronym MLS (macrolide,
lincosamide, streptogramin) resistance.
In some regions of the United
States, a high proportion of CAMRSA isolates are clindamycin resistant. If the proportion of clindamycin resistant MRSA isolates
exceeds 10-15 percent, it is recommended that cindamycin not be
used as empiric treatment of suspected S. aureus infections3.
Although clindamycin should be
used with caution if erythromycin re-
142
recognition of two
distinct genotypes.
Although, with the
exception of clindamycin as mentioned previously,
just about any drug
that is shown on
the C&S report to
be effective against
the particular organism which has
been isolated, can
be selected. Some of the most freThe “D” Test
quently mentioned and prescribed
The “D” test is a double-disc
antibiotics include the later generdiffusion test in which an eryation tetracyclines and trimethothromycin disc is placed 15 mm.
prim/sulfamethoxazole. It should
away from a clindamycin disc on
be noted that few of these drugs
an agar plate inoculated with S. auhave much medical evidence bereus. If inducible resistance is prehind their efficacy as the studies
sent, a flattening of the zone of inhave not been performed on these
hibition around the clindamycin
older compounds. Furthermore,
disc will be seen (Figure 5). This
the FDA has not approved any of
flattened zone of inhibition resemthese older agents as being specifibles the letter “D,” hence the name
cally effective against MRSA. FDA
“D” test. In one study, D tests of
risk categories will help the physi91 clindamcin-susceptible, erycian choose the safest agent for
thromycin resistant, S. aureus isotreatment of MRSA infections in
lates showed that 68% of MSSA
pregnant patients (Figure 6).
and 12.3% of MRSA cultures were
Probably the largest study to date
D test positive4. It is recommended
dealing with this issue was recently
that the clinician contact a micropublished by Ruhe. In his study of
biology laboratory to see if the “D”
24 patients with serious tetracycline
test is routinely performed.
sensitive MRSA infections (67% had
complicated skin and skin structure
Treatment Options
infections) both doxycycline and
Because of the increasing inciminocycline were used. Clinical cure
dence of MRSA and the realization
was achieved in 83% of these pathat there are, in fact, two distinct
tients. Both drugs were well-toleratgenetic strains causing human ined. The conclufection, there has
sion of this study
been a correwas that long-actsponding interest
The “D” test is a
ing tetracyclines
in finding new
may be a reasontherapies against
double-disc diffusion
able treatment althese organisms.
test in which an
ternative6. The reAs discussed in
detail above, not
mainder of this
erythromycin disc is
all MRSA has the
section will deal
placed 15mm away
same susceptibiliwith those drugs
ty patterns. While
that are specificalfrom a clindamycin disc
HA-MRSA is usuly designed and
on an agar plate
ally only treated
approved for use
with non-beta
against MRSA.
inoculated with S. aureus.
lactam antibiotics
specifically deVancomycin
signed to be used
First approved
against MRSA, CA-MRSA is usually
in 1958, vancomycin has long been
susceptible to a wide range of both
the mainstay in the treatment of paold and new drugs.
tients with serious MRSA infections.
Some of these would never
Despite recognized issues with inadhave been considered appropriate
equate tissue penetration, the ability
therapy for MRSA before this
Continued on page 143
sistance is present, it
is possible to have
resistance to erythromycin without
it signifying inducible clindamycin
resistance. To determine if this is the
case, the microbiology laboratory must Figure 5: The “D” test. Note the
perform the “D” flattening of the zone of inhibitest.
tion around the clindamycin disc.
PODIATRY MANAGEMENT • NOVEMBER/DECEMBER 2005
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MRSA...
oxazolidinone antibiotic has been
pancytopenia in pashown in a number of randomized,
tients receiving this drug
to only dose it IV and concerns
controlled clinical trials to be a
for longer than 10 days. This
about toxicity, it has established itvery effective drug for the treatis something that does need to
self as an overall effective and safe
ment of MRSA in complicated SSSI,
be monitored if the patient will be
drug for most MRSA infections. Its
including diabetic foot infections.
on a prolonged course of therapy.
acceptance was further bolstered by
In fact, it is one of a very few anInterestingly, at least two studies
the perception that, quite frankly, it
tibiotics that is specifically FDA-inhave looked at the potential to
was “all there is.” In fact, it was;
dicated for the treatment of diabetcause hematologic adverse events
however, despite
ic foot infections.
versus that for vancomycin. In a
the development
It has the further
study of 686 patients with nosocoof newer agents
advantage
of
mial pneumonia, linezolid-induced
First approved
that have shown
being
100%
thrombocytopenia was found 6.4%
remarkably higher
bioavailable in
of the time. With vancomycin, the
in 1958, vancomycin
efficacy rates and
the oral formulasame was found 7.7% of the time10.
has
long
been
the
rather staggering
tion so its efficaRao looked at patients given long
vancomycin failcy would be comterm therapy for orthopedic infecmainstay in the
ure rates against
parable whether
tions and likewise found that there
treatment of patients
MRSA for skin and
given IV or PO.
were similar hematologic effects
with serious MRSA
skin structure inLooking at
with a trend towards greater effect
fections (SSSI), the
the data, in a
with vancomycin. Also, patients
infections.
drug remains the
comparative trial
placed on vancomycin first, folmainstay of treatof infected foot
lowed by linezolid actually did
ment in many
ulcerations in dihave a higher rate of thrombocyhospitals and in the minds of many
abetic patients, linezolid was comtopenia. All cases were reversible.
physicians. Much of this may be atpared to ampicillin-sulbactam and
tributed to a “comfort zone” situaamoxicillin-clavulanate, and found
Daptomycin
tion where docs have used the drug
to be statistically more effective8.
The second of the newer antifor almost half a century and they
MRSA antibiotics to have data speAgainst vancomycin for complicatare comfortable with it, shortcomcific for SSSI is the cyclic lipopeped SSSI, Weigelt found that microings and all.
biological cures
Furthermore, the cost of some
against MRSA
of the new drugs is quite offwere found with
putting to many physicians, palinezolid 87% of
tients and pharmacies that need to
the time versus
stock the newer, expensive drugs.
only 48% of the
There is also a widely held theory
time with vanthat all new antibiotics should be
c o m y c i n
“reserved” or restricted only to
(p=0.0022)9.
Antibiotic
Category
cases in which “Old Faithful” fails.
Given the suThe problem with this approach is
periority of this
Clindamycin
B
that by the time the new drug is
drug
against
Daptomycin
B
started, the patient may have lost
commonly used
Trimethoprim/sulfamethoxazole
C
limb or life.
antibiotics in
More recently there have been
podiatric mediLinezolid
C
concerns about the development
cine, where does
Vancomycin
C
of tolerance and frank resistance of
this fit? CertainMinocycline
D
staphylococcus to vancomycin.
ly, in patients
Vancomycin Intermediate Staphywith diabetes
lococcus aureus (VISA) was first rewho have MSSA
ported in Japan in 1997. As of
infections, you Antibiotics with activity against MRSA and their FDA risk
2004, there are at least nine reportwould not use categories for pregnancy.
ed cases in the US. Furthermore,
linezolid. Stanthe first reports of vancomycin-retide drug daptomycin. This drug is
dard therapy with a cephalosporin
sistant Staphylococcus aureus
effective against Staphylococcus auor other beta-lactam agent would
(VRSA) was found in patients with
reus-resistant to methicillin, vanbe most appropriate. In patients
diabetic foot ulcerations7.
comycin and linezolid. In its cliniwith diabetes who have a concal trials, daptomycin was tested
firmed MRSA infection, however,
against vancomycin for MRSA isothis drug, even given orally, could
Linezolid
lates and a penicillinase-resistant
very well be statistically more efLinezolid was the first of the
penicillin for MSSA. Of the 902
fective than vancomycin.
newer generation of anti-MRSA anavailable patients, only about 10%
Much has been made about the
tibiotics to have clinical relevance
potential for thrombocytopenia or
to podiatric medicine. This novel
Continued on page 144
FIGURE 6
FDA Risk Categories
for Pregnancy
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MRSA...
had MRSA. Clinical success
rates were 81.1% for daptomycin
vs. 73.8% for vancomycin12. This is
most interesting to again demonstrate the rather significant vancomycin failure rates that have
been found across a range of trials
for different antibiotics. If between
one-quarter to one-half of patients
do not respond on vancomycin can
it still be considered first line therapy? Data specifically against diabetic infections is somewhat sparse in
that only about 12% of this population had a diabetic foot infection.
Daptomycin can only be given
parentally as no PO formulation exists. It does have the theoretical advantage of being considered a bactericidal agent but the validity of
that advantage has been called into
question13. At this point, its use in
podiatric medicine remains to be
elucidated. It could be effective in
more resistant organisms, even
those found resistant to linezolid.
Also, the theoretical advantage of
its bactericidal activity may be useful in osteomyelitis but no studies
yet exist to demonstrate its efficacy.
without the use of specific anticomycin-aztreonam combination in
MRSA antibiotics15.
treating patients with complicated
SSSI.
Looking at CA-MRSA in a more
At least on the surface this
general group of 453 patients, Fridlooks to be an ideal drug for podkin found that initial antibiotic
iatric infections, especially in
therapy that was inactive against
those with severe diabetic foot
CA-MRSA did not increase the
infections.
chance for an adverse outcome
Monotherapy would be usable
versus those that received antibecause combination drug therapy
MRSA antibiotics.
to cover MRSA,
This last secgram negatives
tion emphasizes
and anaerobes
one of the oldest
The latest
would be elimiaxioms of clinical
nated. It may be
infectious disdrug to receive FDA
a bit too early to
eases: It is imporapproval for
get overly enthutant to treat your
siastic, however.
patient and not
the treatment
Careful analysis
the culture reof MRSA SSSI is the
of
this
data
port. If the patetracycline derivative
shows that in the
tient is improvtigecycline group
ing despite a cultigecycline.
of 422 patients,
ture report showonly 83 (<20%)
ing MRSA resishad diabetes and
tant to the preonly 7.1% had infected ulcers. Of
scribed antibiotic, do not change
greatest concern is the incredibly
therapy—monitor the patient.
high rate of gastrointestinal adYes, MRSA is an increasing
verse events. Nausea occurred in
problem. It has become much
34.5% of the patients, vs. 8.2% for
more common than ever before.
the comparator, and vomiting ocFurthermore, we now have the
curred in almost 20% of patients
added challenge of determining
vs. 3.6% for the comparator. It will
whether or not the patient prebe interesting to see how this drug
sents with CA or HA-MRSA. Fortuis positioned and whether or not
nately, new therapies are arriving
more clinical experience bears out
to treat those who really need
the problem with the GI events.
them. ■
Tigecycline
The latest drug to receive FDA
approval for the treatment of MRSA
SSSI is the tetracycline derivative
tigecycline. This drug is particularly
The No Treatment Option
exciting because up to this point all
Although an anathema to
other anti-MRSA drugs have been
many podiatric physicians, there
specifically targeted against gram
comes a time
positive organisms
when no treatonly. Tigecycline
ment may be the
is a broad specLinezolid was
best treatment.
trum agent effecThis is particulartive against a wide
the first of the newer
ly true of MRSA.
range of both sengeneration of
Studies are startsitive and multiing to show that
resistant gram
anti-MRSA antibiotics
just
because
positives, gram
to have clinical
MRSA is cultured
negatives
and
from a wound, it
even anaerobic orrelevance to podiatric
may not be necganisms. In the
medicine.
essary to utilize
pivotal phase 3 trispecific
antials tigecycline was
MRSA therapy.
compared to vanLooking specifically at diabetic
comycin with aztreonam for SSSI14.
foot infections, Dang found that
1,116 patients were enrolled and
although the overall number of
833 were clinically available. Clinipatients growing MRSA doubled
cal response rates were found to be
over a three year period, MRSA
similar between the two arms. The
was eradicated with debridement,
conclusion was that tigecycline was
topical treatment and isolation
as safe and efficacious as the van-
144
PODIATRY MANAGEMENT • NOVEMBER/DECEMBER 2005
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Chambers H. community associated MRSA-resistance and virulence coverage. New England Journal of Medicine.
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Levin T, Suh B, Axelrod T et.al. Potential Clindamycin Resistance in Clindamycin-Susceptible, Erythromycin-Resistant Staphylococcus aureus: Report of
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Weigelt J, Kaafarani HMA, Itani KMF, Swanson RN. Linezolid eradicates MRSA better than vancomycin from surgical site infections. American Journ Surg. 2004 118:760-766
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Rao N, Ziran BH, Wagener MM, Santa ER, Yu VL. Similar
hematologic effects of long term linezolid and vancomycin therapy in a prospective observational study of patients with orthopedic infections. Clin Infect Dis. 2004. 38:1058-64.
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Arbeit RD, Maki D, Tally FP, et al. The safety and efficacy of
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Pankey GA, Sabath LD. Clinical Relevance of bactierostatic
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in the treatment of Dr. Joseph is edigram positive bacteri- tor of the Journal
al infections. Clin In- of the American
fect Dis 2004 March Podiatric Medical
Association and is
38:864-70.
14
Ellis-Grosse EJ, a podiatrist at
Babinchak T, Dartois the Coatesville
N, et al. The efficacy VA Medical CenPA.
Dr.
and safety of tigecy- ter,
cline in the treatment Joseph is author
of skin and skin struc- of Handbook of Lower Extremity Inture infections: Re- fectious Diseases (2nd Ed.).
sults of two doubleblind phase 3 comparison studies with
vancomycin-aztreonam. Clin Infect Dis
2005
Suppl
5.
41:S341-53.
15
Dang
CN,
Prasad YDM, Boulton
AJM, Jude EB. Methicillin resistant Staphylococcus aureus in the
diabetic foot clinic: a
worsening problem.
Diabetic Medicine.
20:159-161 2003.
16
Fridkin SK,
Hageman JC, Morrison MHS, et al. Methicillin resistant
Staphylococcus aureus disease in three
communities. NEJM
352:1436-44, 2005.
www.podiatrym.com
Dr. Kosinski is a
professor in the
Department of
Medicine
and
Chairperson of
the Institutional
Review Board at
the New York
College of Podiatric Medicine. He
is an Instructor in the Department of
Surgery at New York Medical College
and a contributing editor to the Journal of the American Podiatric Medical Association. Dr. Kosinski has lectured and written extensively on
lower extremity infections and is actively involved in clinical research. He
completed a fellowship in Podiatric
Infectious Diseases at St. Michael’s
Medical Center in Newark, NJ, and is
a member of the Infectious Diseases
Society of America.
See instructions and answer sheet
on pages 194-196.
n
ng io
ui at
in uc
nt Ed
Co ical
ed
M
MRSA...
1) Which of the following antibiotics is
active against CA-MRSA?
A) cephalexin
B) minocycline
C) amoxicillin/clavulanate
D) dicloxacillin
2) You are treating an uncomplicated
skin infection in a pregnant patient.
Which of the following antibiotics is the
least safe to use?
A) linezolid
B) vancomycin
C) minocycline
D) daptomycin
3) Which of the following has 100% bioavailable after oral administration?
A) vancomycin
B) linezolid
C) minocycline
D) clindamycin
4) Which of the following antibiotics
cannot be used to treat an MRSA infection?
A) imipenem/cilistatin
B) daptomycin
C) vancomycin
D) linezolid
5) Penicillin binding protein 2a (PBP2a)
is encoded by the
A) erm gene
B) mec A gene
C) MLS gene
D) PVL gene
6) Which of the following antibiotics
cannot be used in a patient with a history of sulfa allergy?
A) minocycline
Continued on page 146
NOVEMBER/DECEMBER 2005 • PODIATRY MANAGEMENT
145
M C
ed on
ica tin
l E ui
du ng
ca
tio
n
E X A M I N A T I O N
B) linezolid
C) trimthoprim/sulfamethoxazole
D) vancomycin
7) CA-MRSA strains contain
which SCCmec types?
A) I
B) II
C) III
D) IV
8) Which drug is active
against MRSA, gram negative
organisms and anaerobes?
A) vancomycin
B) linezolid
C) daptomycin
D) tigecycline
9) Which anti-MRSA drug is
considered bactericidal?
A) vancomycin
B) linezolid
C) daptomycin
D) tigecycline
10) In which site was the
first reported case of VRSA
found?
A) Urinary tract
B) Blood stream infection
C) Diabetic foot ulcer
D) Sacral decubitus
11) Methicillin was first introduced in 1960. The first
strains of MRSA appeared
within
A) One year
B) Five years
C) Ten years
D) Fifteen years
146
(cont’d)
12) Vancomycin intermediate
S. sureus (VISA) was first reported in
A) 1961
B) 1985
C) 1997
D) 2005
13) Which of the following
has shown activity against S.
aureus resistant to methicillin,
vancomycin and linezolid?
A) minocycline
B) TMP/SMX
C) Daptomycin
D) Clindamycin
14) Which of the following is
available in oral form for
treatment of MRSA?
A) linezolid
B) daptomycin
C) vancomycin
D) tigecycline
15) Which of the following is
safest to use in a pregnant patient?
A) linezolid
B) clindamycin
C) trimethoprim/sulfamethoxazole
D) vancomycin
16) The “D” test is used to
detect
A) inducible clindamycin
resistance
B) resistance to methicillin
C) susceptibility to erythromycin
D) susceptibility to daptomycin
PODIATRY MANAGEMENT • NOVEMBER/DECEMBER 2005
17) Which of the following
has shown reliable activity
against hospital acquired
MRSA (HA-MRSA)?
A) Clindamycin
B) TMP/SMX
C) Tetracycline
D) Vancomycin
18) Which is true about community-acquired MRSA (CAMRSA)?
A) It is sensitive to antibiotics except beta-lactams
B) It produces fewer toxins
than HA-MRSA
C) It rarely produces panton valentine leukocidins
(PVL)
D) It is associated with
mec A type I, II, III
19) Resistance to which of the
following antibiotics implies
resistance to methicillin?
A) oxacillin
B) erythromycin
C) clindamycin
D) cephaolthin
20) Penicillin was introduced
for clinical use in
A) 1938
B) 1941
C) 1952
D) 1956
SEE INSTRUCTIONS
AND ANSWER SHEET
ON PAGES 194-196
www.podiatrym.com