Community-acquired MRSA

Transcription

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INSIDE
Epidemiology
Pathogenesis
Clinical
presentation
Diagnosis
Treatment
Guide to important
clones of MRSA
the author
Community-acquired MRSA
Introduction
PREVIOUSLY only a problem in
hospitals, infection with methicillin-resistant Staphylococcus aureus
(MRSA) has now become commonplace in the general practice setting.
A common cause of skin and soft
tissue infections, MRSA is resist-
ant to most beta-lactam antibiotics, which have been the mainstay
of therapy for such infections for
many years.
Along with this emergence in
the community, there has been
some evidence for a change in dis-
ease presentation, in particular an
increase in skin and soft tissue infections (often recurrent) and severe
pneumonia. Initially restricted to
particular ethnic groups, MRSA in
the community now crosses demographic boundaries. The resistance
patterns of community strains of
MRSA are also evolving, making
empiric antibiotic choices difficult
and reinforcing the importance of
laboratory testing.
cont’d next page
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Dr Matthew O’Sullivan
staff specialist in infectious
diseases and medical
microbiology, Westmead
Hospital and senior lecturer,
Sydney Emerging Infections and
Biosecurity Institute, University
of Sydney.
Copyright © 2013
Australian Doctor
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PAGE 42
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19 July 2013 | Australian Doctor |
25
How To Treat – Community-acquired MRSA
Epidemiology
Figure 1: Proportion of MRSA among S.
aureus infections from the community.
Evolution of MRSA
Shift from hospital to
community-acquired infection
Data from the Australian Group on Antimicrobial
Resistance, Staphylococcus aureus program
2010 (www.agargroup.org).
40
35
CA-MRSA clone
30
Percentage
LIKE other bacteria, Staphylococcus aureus has evolved resistance
mechanisms in response to the
introduction of anti-staphylococcal antibiotics into healthcare.
When penicillin was introduced
during World War II, all S. aureus
strains were susceptible, but the
first penicillin-resistant isolates
were reported in 1945, mediated by a beta-lactamase enzyme
encoded by a gene located on a
mobile plasmid. Subsequently,
semi-synthetic penicillins were
introduced that were resistant to
degradation by the beta-lactamase
enzyme — first methicillin, and
later flucloxacillin and dicloxacillin.
Resistance
to
methicillin
emerged in 1961, mediated by
a gene (mecA), which encodes a
modified penicillin binding protein, the target of the beta-lactam
antibiotics. This resistance mechanism confers resistance to all
beta-lactam antibiotics including
carbapenems and cephalosporins
(with the exception of newly developed extended spectrum cephalosporins such as ceftaroline). The
mecA gene and associated regulatory genes are located on a mobile
genetic element known as Staphylococcal Cassette Chromosome
mec (or SCCmec), of which several
genetic types have been described.
HA-MRSA clone
25
20
15
10
5
0
ACT
NSW
NT
QLD
SA
TAS
VIC
WA
State
The past three
decades have seen
a dramatic shift in
the epidemiology of
MRSA infection, with
infections developing
in those without
previous contact with
the healthcare system.
When MRSA first emerged in the
1960s, it was restricted to the hospital environment (HA-MRSA),
where broad-spectrum antibiotic
use is most common. It quickly
spread to become a major cause of
hospital-acquired infections worldwide. The SCCmec elements carried
by MRSA strains common in hospitals frequently carry genes conferring resistance to other antibiotics
(such as macrolides, tetracyclines
and aminoglycosides). As such,
these HA-MRSA clones are often
referred to as multi-resistant MRSA.
The past three decades have seen
a dramatic shift in the epidemiology
of MRSA infection, with infections
developing in those without previous contact with the healthcare system (CA-MRSA). Some of the first
reports of this phenomenon were
from Australia in the 1980s, but it
was also observed in several other
continents around the same time.
These CA-MRSA clones tended
to first emerge in settings of overcrowding, social disadvantage, poor
hygiene and/or poor access to medical care. It soon became evident
that CA-MRSA clones are genetically distinct from HA-MRSA.
Importantly, while they carry
SCCmec and are resistant to
beta-lactam antibiotics, they are
often not resistant to some of the
non-beta-lactam antibiotics sometimes used to treat staphylococcal
infections (such as clindamycin,
trimethoprim-sulfamethoxazole
and tetracyclines). Hence CAMRSA isolates are often referred
to as non-multi-resistant. The
SCCmec elements of these clones
is distinct from that carried by the
HA-MRSA, being generally smaller
in size and therefore potentially
conferring greater mobility with
lower fitness cost to the organism as a result. It is also evident
that there are many different CAMRSA clones, which have arisen
by the acquisition of SCCmec by
methicillin-susceptible isolates of S.
aureus on numerous occasions in
many regions of the world.
MRSA in Australia
Much of the knowledge of the
epidemiology of CA-MRSA in
Australia comes from periodic
surveys that have been performed
by the Australian Group on Antimicrobial Resistance (see Online
resources, page 31).
In these surveys, participating
microbiology laboratories from
around Australia each submitted
up to 100 consecutive clinical isolates of S. aureus alternating on a
yearly basis between isolates from
patients in hospital and patients
in the community. These surveys
have indicated that the proportion
of S. aureus isolates that are due to
MRSA from community patients
has been increasing, reaching 18%
in 2010. However, this proportion is not geographically uniform,
ranging from 5% in Tasmania to
35% in the NT (figure 1).
Furthermore, HA-MRSA clones
infecting patients presenting from
the community (mostly in those
with previous healthcare contact), rather than true CA-MRSA
(in patients with no healthcare
contact) account for 33% of the
community burden of MRSA
infection overall, but this figure
also varies from state to state.
When CA-MRSA first emerged
in Australia, it was linked to remote
Aboriginal communities in the Kimberley region of WA. At the same
time, CA-MRSA was emerging in
Aboriginal communities in the NT.
In Eastern Australia, a different
CA-MRSA clone emerged in the
late 1990s in individuals of Pacific
Islander background; the same
clone had previously caused an
epidemic in Pacific Islander communities in New Zealand. For some
time after their appearance, cases
in individuals from other ethnic
backgrounds were unusual, however subsequent dissemination of
these strains throughout the population means that, while still a significant risk factor, ethnicity cannot
be relied upon to distinguish CAMRSA from methicillin-susceptible
S. aureus (MSSA) infection.
Pathogenesis
Colonisation
STAPHYLOCOCCUS aureus is
a common skin commensal, with
up to 20-30% of individuals carrying the organism at any one time.
This figure is relatively constant
across geographic areas and racial
groups. It seems that some individuals have a genetic predisposition to S. aureus carriage, while
others have an inherent protection
against it. Common sites of colonisation include the nares, axillae,
groin and throat.
Animals can also be a reservoir of
MRSA. While strains of S. aureus
that colonise and infect animals are
generally genetically distinct from
those affecting humans, there are
important exceptions. Household
pets have sometimes been found to
be carriers of human CA-MRSA
26
| Australian Doctor | 19 July 2013
and horses is common. The farmers
and veterinarians in close contact
with these animals are at risk of colonisation and infection from these
livestock-associated MRSA (LAMRSA) strains. To date, LA-MRSA
has not been recognised as a major
problem in Australia.
Transmission
strains, in association with recurrent infection in their owners that
has been refractory to decolonisa-
tion therapy. In some regions of the
world, carriage of particular strains
of MRSA in livestock such as pigs
CA-MRSA, like other S. aureus
strains, is acquired by skin to skin
contact with a colonised individual, or by contact with contaminated fomites or environmental
surfaces. Thus CA-MRSA infections among multiple members
of a household is common. Outbreaks of CA-MRSA have also
been reported in sporting teams,
thought to be through repeated
skin contact during the course of
games (facilitated by skin abrasions), or through the sharing of
sporting equipment or towels.
Vertical acquisition by neonates
secondary to maternal colonisation is also recognised.
The organism gains access to
the subcutaneous tissues through
breaks in the epithelium (sometimes not clinically evident),
whereupon a localised skin or
skin structure infection may ensue.
Invasion into blood vessels can
lead to bacteraemia with or without a metastatic focus, often without a primary skin infection being
evident. An alternate possible
mode of acquisition of infection is
through aspiration or inhalation
to cause lower respiratory tract
infection.
cont’d page 28
from page 26
Figure 2:
Mechanisms of
Panton–Valentine
leukocidininduced acute
lung injury and
lung inflammation.
Black arrows
indicate observed
events; yellow
arrows indicate
postulated events.
Evasion of host defences
S. aureus carries several virulence
factors that contribute to pathogenesis. One important virulence
factor is Panton–Valentine leukocidin (PVL). This is a pore-forming exotoxin, encoded by genes
located on a mobile bacteriophage.
It causes lysis of leukocytes, but
also causes neutrophil activation
and release of pro-inflammatory
cytokines (figure 2). It is thought
to be important in the pathogenesis of necrotising pneumonia, and
possibly severe skin and soft tissue
infections. However, no association has been shown with bacteraemia or endocarditis.
Panton–Valentine
leukocidin
can be produced by MRSA or
MSSA, although while it is produced by many of the clones that
are associated with CA-MRSA
infection, it is relatively rarely
produced by MSSA (about 2%
of isolates in some series) or
HA-MRSA. Infection with PVLproducing MRSA clones is agerelated, occurring more commonly
in younger age groups, suggesting
the possibility that development
of immunity to these clones, or
perhaps PVL itself, can protect
against infection.
Image courtesy of
PNAS1
Clinical presentation
Localised infection
Figure 3.
Furuncle near
right knee.
CA-MRSA causes the same range
of infections that are associated
with MSSA and it is not possible
to differentiate infection due to
either organism based on clinical findings. The most common
presentations in general practice
are skin and soft tissue infections,
such as furuncles (boils) (figure 3),
abscesses and wound infections,
and impetigo.
Image courtesy of
Elsevier2
Disseminated infection
Common metastatic foci include
endocarditis, septic arthritis, pyomyositis, osteomyelitis and vertebral discitis. These conditions are
frequently the presenting problem, without a history of earlier
skin infection. Endocarditis often
affects those with risk factors (IV
drug users, pre-existing valvular
disease), but is also common in
those without identifiable risk factors. Up to 30% of patients with S.
aureus bacteraemia, without clinical evidence of endocarditis, are
found to have cardiac vegetations
when examined by echocardiogram. This is even more likely in
those with pre-existing valvular
disease or prosthetic valves. Likewise, the seeding of prosthetic
joints and other indwelling devices
is a common scenario in those
with S. aureus bacteraemia, and
should always be considered in the
workup of such patients. Necrotising fasciitis and septic thrombophlebitis have also been associated
with CA-MRSA infection.
Necrotising pneumonia due
to CA-MRSA can be a devastating condition. It classically presents with fever and leukopenia,
progressing to dyspnoea, cough,
haemoptysis and shock. Chest
X-ray on presentation often shows
multilobar infiltrates sometimes
with cavity formation (figure 4).
28
Figure 4.
Chest
radiograph
in a case of
CA-MRSA
community
acquired
necrotising
pneumonia
showing
bilateral dense
infiltrates.
Image courtesy of
Annals of Intensive
Care3
This syndrome, while relatively
rare, carries a high mortality, and
often affects young adults with no
previous medical history. In some,
but not all, of these cases, a preceding infection with influenza has
been identified.
Patients with one focus of suspected staphylococcal infection
should also be assessed for the possibility of metastatic foci. Fever,
tachycardia and hypotension may
indicate bacteraemia, and such
patients must be examined for features of endocarditis (murmurs,
cardiac dysfunction, splinter haemorrhages). An examination for
osteoarticular infections should
also be performed, especially in
individuals with prosthetic joints.
Back pain in these patients often
turns out to be due to discitis or
epidural abscess, so a careful history and examination for spinal tenderness or evidence of spinal cord
compression should be undertaken
if back pain is present.
Recurrent infection
Recurrent disease after initial successful treatment, often at a different body site, is a particularly
troublesome problem, and may be
more common with CA-MRSA
strains. The most common scenario
involves recurrent furunculosis.
While the initial therapy eliminates
the first episode of infection, skin
colonisation with the organism
often persists, thereby increasing
the risk of recurrent episodes. It
may also occur due to re-acquisition
from colonised household contacts
or domestic pets. Diabetes is a risk
factor for recurrent disease, and
fasting glucose levels should be
obtained in such patients, though
the majority of cases occur in nondiabetics without any evidence of
immunodeficiency.
cont’d page 30
Diagnosis
SINCE infections due to CAMRSA are clinically indistinguishable from those due to methicillin
susceptible S. aureus, and given
the significant rates of CA-MRSA
now occurring, collection of
appropriate samples for culture is
an important part of management
for any suspected staphylococcal
infection. For skin and soft tissue
infections, aspiration or incision
and drainage to obtain a specimen
of pus for culture is ideal.
More invasive manifestations
are best investigated and treated in
a hospital setting. Blood cultures
should be collected (before antibiotic therapy, where feasible) if bacteraemia, endocarditis, pneumonia,
osteoarticular or spinal infection is
suspected, along with appropriate
radiological investigations. Bone
scans are a sensitive method for
detection of osteomyelitis and spinal discitis, but urgent spinal MRI
is preferable if spinal cord compression is suspected clinically. Transoesophageal echocardiography (TOE)
Figure 5. Gram
stain of a
sputum sample
showing grampositive cocci,
suggestive of
Staphylococcus
sp.
Image courtesy of
Elsevier4
is superior to transthoracic echocardiography (TTE) for detection of
endocarditis, but a TTE may be per-
formed initially if TOE is not readily
available.
Sputum specimens should be
collected in cases of pneumonia
to look for Gram-positive cocci in
clusters suggestive of Staphylococ-
cus sp. (figure 5).
Susceptibility testing is important not only to distinguish MSSA
from MRSA, but also to define
what agents are active for MRSA
isolates, since this can vary widely
from strain to strain. When they
first emerged, CA-MRSA strains
were reliably susceptible to most
non-beta-lactam
antistaphylococcal antibiotics, but unfortunately this is no longer the case,
and definitive management must
involve susceptibility testing.
To determine colonisation status, multiple body sites should
be swabbed for the highest yield.
These include the anterior nares,
axillae, groin, throat and perineum. Any ulcers or other wounds
should also be swabbed. Many
laboratories now use rapid, PCRbased methods for detection of
MRSA colonisation from such
samples. Detection of MSSA or
susceptibility testing from such
samples may not be performed
unless specifically requested.
Treatment
Empirical treatment
REMOVAL of the focus of infection is an effective way to treat
staphylococcal infection. For many
conditions presenting in the general
practice setting, incision and drainage is an important therapeutic
measure, and is often curative for
smaller furuncles and abscesses.
The decision to treat a suspected
staphylococcal infection as MSSA
or MRSA while waiting for susceptibility results will depend on
the local prevalence of CA-MRSA
infection and the severity of the presenting problem. If the prevalence
is low, and for non-severe infection,
oral dicloxacillin (or cephalexin for
mild penicillin allergy, clindamycin
for type I penicillin hypersensitivity) is a reasonable choice to cover
MSSA while awaiting results of
culture.
If MRSA is to be covered empirically, clindamycin is a reasonable
choice, although some CA-MRSA
isolates are resistant to this agent.
Furthermore, it must be remembered that one-third of MRSA isolates from patients presenting in the
community are due to HA-MRSA
clones, which are commonly multiresistant. In patients who are at
risk of HA-MRSA infection by
virtue of previous contact with hospitals, clindamycin may be ineffective.
Oral formations are suitable for
the majority of S. aureus skin and
soft tissue infections presenting in
general practice. Cases of suspected
bacteraemia or other deep infection require IV therapy and such
patients should be referred urgently
to an ED for investigation and
management.
Antibiotic treatment options
Clindamycin
This drug is active against most
CA-MRSA strains, although resistance has been increasing in recent
years. It has high oral bioavailability. It acts at the ribosome to
prevent peptide production, and
30
rifampicin should never be used
as monotherapy. The addition of
a second agent (most often fusidic
acid) helps ‘protect’ the rifampicin
against the development of resistance mutations. Another disadvantage of rifampicin is the potential
for drug interactions. It is a potent
inducer of cytochrome p450
enzymes and must be used in caution with patients who are on drugs
which are metabolised by this
enzyme, such as warfarin, opioids,
oral contraceptives and anticonvulsants. Rifampicin is not subsidised
by the PBS. The standard dose for
S. aureus infection is 300mg twice
daily.
may have a theoretical advantage
of inhibiting production of toxins
such as Panton–Valentine leukocidin.
It is available as 150mg capsules,
and 300-450mg three or four times
daily is the usual dose for adults. IV
formulations of clindamycin and
the closely related lincomycin are
also available.
Possible adverse effects of clindamycin use include nausea, vomiting
and diarrhoea, and is a risk factor
for Clostridium difficile infection. It
is important to note that most isolates that are erythromycin-resistant have inducible resistance to
clindamycin; erythromycin-resistant isolates should not be treated
with clindamycin unless inducible
resistance has been excluded by the
microbiology laboratory.
Trimethoprim-sulfamethoxazole
This is another agent that is frequently active against non-multiresistant MRSA strains. The usual
adult dose is one double-strength
tablet (160mg/800mg) twice daily,
but it requires dose reduction in
renal impairment. It is also available as an oral suspension, so it is a
very useful agent for paediatric CAMRSA infections. Adverse effects
include allergic reactions, bone
marrow suppression and hyper-
kalaemia. These adverse events are
more common and severe in elderly
patients, in whom it should be used
with caution. Trimethoprim-sulfamethoxazole should not be used
in the first trimester and in the last
month of pregnancy.
Doxycycline
Some CA-MRSA strains are also
susceptible to doxycycline. The use
of this agent in CA-MRSA infection
has been less commonly reported
to date, but it remains an option if
clindamycin or trimethoprim-sulfamethoxazole cannot be used, and
the organism shows susceptibility
on laboratory testing.
It is given at a dose of 100mg
twice daily. Adverse effects include
oesophagitis and gastritis, as well
as photosensitivity. It should be
taken with at least 100mL of liquid, and preferably with food. It is
contraindicated in children up to
the age of eight, and in the latter
half of pregnancy due to the possibility of tooth discolouration.
Rifampicin
Rifampicin is also active against
S. aureus, including most MRSA
strains. A major disadvantage
is that resistance develops easily, through point mutations in
the rpoB gene of the organism, so
Fusidic acid
Fusidic acid (or sodium fusidate)
has a novel mechanism of action,
inhibiting bacterial protein synthesis at the ribosome by blocking the
enzyme elongation factor G, and
so also reduces bacterial production of toxins such as PVL. As with
rifampicin, resistance develops easily through point mutations and so
it should not be used as monotherapy. The usual adult dose is 500mg
three times daily.
The main adverse effect is gastrointestinal intolerance. Importantly,
fusidic acid interacts with ‘statin’
cholesterol-lowering agents. Fatal
rhabdomyolysis has been associated with the co-administration of
these drugs, and so statin therapy
should be withheld if fusidic acid is
to be prescribed.
Linezolid
This agent is active against most
MRSA strains, including multiresistant HA-MRSA. Like clindamycin and fusidic acid, it is also
active at the ribosome, and so
may also inhibit the production of
toxins such as PVL. It is available
orally and in an IV formulation,
and is usually administered at a
dose of 600mg twice daily. Important adverse effects include reversible bone marrow suppression and
irreversible neuropathy (including optic neuropathy), although
these most commonly occur with
prolonged use (in excess of four
weeks). It has a number of drug
interactions, including with serotonergic agents (such as SSRIs and
tricyclic antidepressants) to produce serotonin syndrome, so it is
contraindicated with these agents.
Resistance develops through
point mutation, and has occasionally been reported while on therapy.
Linezolid is not subsidised on
the PBS. Given its cost and toxicity profile, it is best prescribed in
consultation with an infectious diseases physician.
Moxifloxacin
Moxifloxacin is a quinolone antibiotic that has activity against
gram-positive organisms, including
some strains of MRSA. It has been
shown to have similar success to
comparators in skin and soft tissue
infections, but the clinical data for
MRSA specifically are minimal. It
is given at a dose of 400mg daily,
oral or IV.
Moxifloxacin can cause QT
elongation and should be used
with caution when given with other
medication that can cause this. Quinolone antibiotics have also been
associated with tendon inflammation and rupture. It is not available
on the PBS, so can be costly.
Resistance develops most commonly through point mutations.
As a result, moxifloxacin is best
reserved for cases with resistance,
hypersensitivity or intolerance of
other agents. It is best prescribed
in consultation with an infectious
diseases physician.
IV antibiotics
Vancomycin has been the mainstay
of IV therapy for severe MRSA
infections since they first emerged
in the 1960s. Unfortunately treatment failure is frequently seen (in
up to 25% of cases of MRSA bac-
teraemia). This can be improved
with adequate source control
(eg, surgical debridement of the
infected site) and with therapeutic
drug monitoring to ensure adequate levels.
In recent years, strains of MRSA
with increased minimum inhibitory concentrations to vancomycin
have emerged that are associated
with higher rates of treatment
failure. At the same time, alternative agents have been brought to
market. None of these have yet
been clearly shown to be superior
to vancomycin in primary randomised clinical trials, but they
are useful alternatives where failure with, or intolerance to, vancomycin has occurred. These agents
include linezolid, moxifloxacin
(both discussed above), daptomycin, tigecycline and ceftaroline.
The latter three are only available as IV therapy. Daptomycin
is ineffective in respiratory tract
infections due to inactivation by
pulmonary surfactant. Ceftaroline is a newly licensed, extended
spectrum cephalosporin, the first

beta-lactam agent with activity
against MRSA.
Duration of therapy
There are no clear recommendations for the duration of therapy
for skin and soft tissue infections.
The decision to discontinue antibiotics is based on the resolution of
signs and symptoms of infection.
Bacteraemia, pneumonia, endocarditis and osteoarticular infections require weeks of IV therapy
followed, in some cases, by oral
treatment. Such infections should
be managed by infectious diseases
specialists.
Decolonisation
Decolonisation is the process of
eradicating carriage of S. aureus in
an attempt to prevent future episodes of infection in known carriers or their contacts.
Attempts at decolonisation
are frequently unsuccessful, and
baths. The most published experience has been with chlorhexidine,
but a recent trial comparing it with
diluted bleach baths (15-minute
soak in bathwater mixed with ¼
cup of 6% sodium hypochlorite)
suggested bleach may be a superior
alternative.
Triclosan has not been used in
any large prospective studies, but
is frequently utilised in Australia.
Some regimens have also added a
0.2% chlorhexidine mouth rinse
three times daily.
Household cleaning
During the period of decolonisation therapy, all bedclothes and
towels should be subjected to a
hot-water wash. Thorough cleaning of household surfaces should
also be undertaken.
widespread use of decolonisation
strategies leads to the development
of resistance to the agents used.
Therefore, decolonisation is only
warranted where patients are suffering from frequent recurrences of
staphylococcal infection (especially
recurrent furunculosis), or where
known carriers are to undergo
high-risk surgical procedures (such
as cardiac surgery or joint replacement).
In some jurisdictions, colonised
healthcare workers are also given
decolonisation therapy before they
can start work.
The patient’s home environment
and household contacts should
also be considered as part of decolonisation strategies. Frequently,
other household members also give
a history of staphylococcal infection, and even if this is not present,
they may be asymptomatic carriers
who can serve as a reservoir for
reinfection of the index patient.
Decolonisation should not be
attempted while active infection
is present, since it is more likely
to be unsuccessful at that time.
Instead, the active infection should
be treated and decolonisation
instituted once the infection has
resolved. The optimal regimen for
decolonisation has not been established, and failure rates, as measured by persistent colonisation or
recurrence of infection are high in
many clinical studies.
The recommended strategies
usually consist of topical antibiotics, antiseptic skin wash, household cleaning and consideration
for oral antibiotics.
Mupirocin nasal ointment (2%)
This is applied three times daily to
the anterior nares.
Antiseptic skin wash
This should be used daily. A number of agents are available for this
purpose, including 4% chlorhexidine, triclosan and dilute bleach
Oral antibiotic therapy
The decision to add oral antibiotic
therapy to the decolonisation regimen will depend on the severity of
the infections caused by the colonising microbes and whether there
have been previous unsuccessful
attempts at decolonisation. If antibiotics are used, rifampicin with a
second active agent (such as clindamycin or fusidic acid) is usually
recommended.
The optimal duration of therapy has not been established. Ten
days is commonly recommended,
though some studies used five or
seven days and one noncomparative study used a 60-day regimen,
with good results.
Testing for success of decolonisation with screening swabs is
not routinely performed, except
if required for healthcare workers planning to return to work.
Instead, repeat decolonisation
would be attempted if further clinical infection occurred.
Further information regarding
decolonisation,
including
fact sheets for patients, is available from the WA Department
of Health’s website (see Online
resources, right).
Online resources
Australian Group on
Antimicrobial Resistance
www.agargroup.org
WA Department of Health
Information on decolonisation
www.public.health.wa.gov.
au/3/896/3/camrsa.pm
References
1. D
iep B, et al.
Polymorphonuclearleukocytes
mediate Staphylococcus aureus
Panton-Valentine leukocidin
induced lung inflammation
and injury. Proceedings of the
National Academy of Sciences
USA 2010; 107:5587-92.
2. Z
etola N, et al. Communityacquired meticillin-resistant
Staphylococcus aureus: an
emerging threat. Lancet
Infectious Diseases 2005;
5:275-86.
3. K
reienbuehl L, et al.
Community-acquired necrotizing
pneumonia due to methicillinsensitive Staphylococcus aureus
secreting Panton-Valentine
leukocidin: a review of case
reports. Annals of Intensive Care
2011; 1:52.
4. F
ile TM. Case studies of lower
respiratory tract infections:
community-acquired pneumonia.
American Journal of Medicine
2010; 123:S4-S1.
A guide to important clones of MRSA
THERE are many ways of typing
strains of MRSA, but the most
widely accepted way of identifying MRSA clones is through multilocus sequence typing (MLST)
where organisms are assigned
a numerical sequence type (ST)
according to the DNA sequence
of seven housekeeping genes. The
structure of the SCCmec (assigned
a Roman numeral I through to XI)
is combined with the MLST to further characterise the clone.
ST239-III (AUS2/3)
This clone is a major HA-MRSA
clone in Australia. It is multiresistant, but frequently remains
susceptible to rifampicin and
fusidic acid. Until recently it was
responsible for the majority of
HA-MRSA infections in Australia,
but has recently been overtaken by
ST22-MRSA-IV (EMRSA-15). It
is usually PVL negative.
ST22-IV (EMRSA-15)
This clone first emerged in Europe
in the 1980s and appeared in Australia soon after. It is also a major
HA-MRSA clone, and has recently
overtaken ST239-MRSA-IV as the
most common HA-MRSA clone
in Australian hospitals. It is also
common in long-term care facilities. It is characteristically resistant
to ciprofloxacin, but is otherwise
non-multi-resistant.
Classically,
this clone does not produce PVL,
but recently a PVL-producing
ST22-MRSA-IV clone has been
reported from multiple sites around
the world, including Australia. This
PVL-carrying clone has a different
antimicrobial resistance profile, and
probably evolved separately from
the EMRSA-15 clone.
ST93-IV (Queensland clone)
This clone was first reported from
the Queensland city of Ipswich,
but has since spread to be the most
common CA-MRSA clone in Australia. It typically produces PVL
and is non-multi-resistant, but
rates of clindamycin resistance are
increasing in this clone. It has been
associated with a number of severe
manifestations including necrotising pneumonia, spinal infection
and septic thrombophlebitis.
may represent a new subspecies.
ST30-IV (South West Pacific,
Oceania or Western Samoan
Phage Pattern clone)
ST8-IV (USA300)
This clone appears to have arisen
in the Pacific Islands, spread to
New Zealand, and subsequently
in Pacific Islander communities in
Australia. However, it is no longer
restricted to this ethnic group.
Like ST-93-MRSA-IV it generally
produces PVL, is non-multi-resistant, and is associated with severe
disease manifestations.
ST1-IV (WA-MRSA-1)
This CA-MRSA clone was one of
the first to emerge in Australia and
remains a dominant clone in WA.
It does not typically produce PVL.
ST75-IV
A CA-MRSA clone largely limited in distribution to Aboriginal
communities in the NT and WA,
and associated with skin and soft
tissue infections. It does not produce PVL. This clone is genetically
divergent from other S. aureus and
This PVL-producing clone is the
dominant CA-MRSA clone in
North America. Like ST93 in
Australia, it has been associated
with severe disease manifestations,
including lethal necrotising pneumonia. Antibiotic resistance in this
clone is increasing, and it has also
been reported in Europe. Cases of
this clone have been reported in
Australia, sometimes linked with
travel to the US, but it remains less
common than other CA-MRSA
clones.
ST398-IV and ST398-V (LA-MRSA)
This is a livestock-associated
MRSA clone that has recently
emerged in Western Europe as a
cause of infection in pig farmers
and other individuals in contact
with colonised livestock. It has
been identified in a number of
sites around the world, but colonisation of livestock in Australia has
not been shown to be a problem
thus far.
cont’d next page
19 July 2013 | Australian Doctor |
31
Summary
Case study
MRSA now causes about 20% of
Staphylococcus aureus infections
presenting in the community (twothirds of which are CA-MRSA
clones), but there is substantial
geographic variation in these figures.
Cultures should always be
obtained in cases of suspected
staphylococcal infection to guide
antibiotic therapy.
Incision and drainage should be
performed where possible for skin
and soft tissue infections.
Treat for MRSA before sensitivity results are available when
the presenting problem is severe
and/or the local incidence of CAMRSA infection is high.
Clindamycin remains active in
the majority of CA-MRSA isolates.
Trimethoprim-sulfamethoxazole
is an alternative, and a number of
other oral agents are available.
Bacteraemic spread of infection
should be suspected in those who
are systemically unwell, complain
of joint or back pain, have indwell-
ing prosthetic devices, or cardiac
valvular disease or peripheral stigmata of endocarditis. Collection of
blood cultures prior to initiation
of antibiotic therapy and prompt
hospital emergency department
referral is warranted.
Consider the possibility of
CA-MRSA in cases of severe
community-acquired
pneumonia, particularly with multilobar
disease, haemoptysis or preceding flu-like illness in previously
healthy adults.
Decolonisation should only be
attempted sparingly. There is little guidance from the literature
regarding patient selection or specific regimens. It is reasonable to
provide decolonisation therapy to
patients presenting with frequent
recurrences of S. aureus skin infections, but it is not recommended
after a single episode of infection.
Decolonisation is usually unsuccessful in patients with active
infection or active skin conditions
such as eczema.
A 32-YEAR-old man presents with
a 2cm erythematous, tender, indurated lesion on his distal thigh, suggestive of a furuncle (figure 3, page
28). He reports that he has had five
similar skin lesions at other sites on
his limbs and his lower abdomen
over the past 12 months. Each of
these have been treated with dicloxacillin or cephalexin but despite this
they have enlarged, spontaneously
discharged purulent material and
then taken several weeks to heal.
Scarring is evident in each of the
sites of these previous infections.
CA-MRSA infection is suspected.
The lesion is not currently fluctuant
or discharging so incision and drainage of the lesion is not performed.
Swabs are collected from the anterior nares, groin throat and axilla
for culture and susceptibility testing.
Clindamycin 450mg three times a
day is started empirically. Fasting
blood glucose is normal.
The patient returns five days
later for review. The screening
swabs have yielded a light growth
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Community-acquired MRSA —
19 July 2013
1. Which TWO statements are correct
regarding epidemiology of MRSA?
a) C
ommunity-acquired MRSA is found only in
particular identifiable ethnic groups
b) A significant percentage of MRSA in the
community are hospital-acquired MRSA
c) T
he Panton–Valentine leukocidin (PVL)producing MRSA infects mainly older patients
d) More than 20% of the population carry S.
aureus at any one time
regarding the aetiology, pathology and
genetics of community-acquired MRSA
infection?
a) P
VL is a virulence factor that can form pores
in cells, causing lysis of leukocytes
b) PVL is the toxin that causes MRSA
bacteraemia and endocarditis
c) B
eta-lactam antibiotic resistance in MRSA
is mediated through genes located on the
SCCmec genetic element
d) The body sites most commonly colonised by
MRSA are the exposed hands and forearms
regarding the pathophysiology of
community-acquired MRSA?
a) C
ommunity-acquired MRSA most commonly
causes skin and soft tissue infections
b) Community-acquired MRSA has a distinct
clinical presentation different from
methicillin-sensitive S. aureus
c) M
RSA can survive on, and be acquired from,
living hosts only
of S. aureus, resistant to flucloxacillin and cephalexin but sensitive
to clindamycin and trimethoprimsulfamethoxazole. There has been
improvement in the swelling and
erythema of the lesion, and it
remains non-fluctuant and is not
discharging.
Clindamycin is continued for a
further five days. At this time, the
lesion has resolved without scarring.
Decolonisation therapy is instituted
with 2% mupirocin nasal ointment
and 4% chlorhexidine body wash
for 10 days.
Three months later, the patient represents with a similar lesion on the
opposite thigh. He is again started
on oral clindamycin with good resolution, and again screening swabs
show the presence of MRSA with
the same sensitivity pattern.
On questioning, his 12-year-old
son has also had skin infections over
the past 12 months. Screening swabs
of his wife and three children show
MRSA colonisation (with the same
susceptibility profile) in his wife and
12-year-old son.
Repeat decolonisation of the
patient with concurrent decolonisation of his wife and all three children
is performed. No further skin infections in any family members are
subsequently reported.
This case highlights the difficulty of recurrent furunculosis, a
common problem in general practice, which can be due to methicillinsusceptible or methicillin-resistant
strains of S. It is important to consider carriage in family members in
such cases. Failure of decolonisation
is common, and repeated attempts
are often required.
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d) Animals can be a reservoir for MRSA
but livestock-associated MRSA is not a
significant problem in Australia
4. W
hich TWO statements are correct
regarding the presentation of communityacquired MRSA?
a) Common metastatic foci of communityacquired MRSA include endocarditis and
vertebral discitis
b) Necrotising fasciitis, septic thrombophlebitis
and necrotising pneumonia have all been
associated with community-acquired MRSA
c) If treated successfully and properly,
community-acquired MRSA should not recur
d) Recurrent community-acquired MRSA
occurs only in diabetic or immunodeficient
patients
5. W
regarding the investigation of communityacquired MRSA?
a) Community-acquired MRSA may be treated
empirically without susceptibility testing
b) Susceptibility testing is routinely performed
on swabs for MRSA colonisation by the
pathology laboratory
c) Blood cultures and appropriate imaging is
indicated if bacteraemia is suspected
d) Ideally, pus culture should be obtained for
boils
6. W
regarding the treatment of communityacquired MRSA?
a) Incision and drainage is the treatment of last
resort after pharmacotherapy is exhausted
b) Clindamycin is a reasonable antibiotic
choice for empirical therapy
c) Clindamycin will adequately treat more than
90% of MRSA infections presenting in the
community
d) Suspected bacteraemia or deep infection
should be referred urgently to the hospital
for IV antibiotics
regarding the medications used to treat
community-acquired MRSA?
a) Clindamycin may predispose to Clostridium
difficile infection
b) A trial of rifampicin monotherapy should be
given before the addition of fusidic acid
c) Trimethoprim-sulfamethoxazole is a useful
antibiotic for paediatric community-acquired
MRSA
d) Doxycycline is a useful antibiotic for
paediatric community-acquired MRSA
8. Boris is a 32-year-old man with a fever
and community-acquired MRSA in blood
cultures. Which TWO statements are
correct?
a) Back pain should prompt a careful history
and examination for spinal tenderness or
evidence of spinal cord compression
b) Boris is unlikely to have endocarditis if he
has no clinical signs of it
c) Necrotising pneumonia affects elderly
patients and is unlikely even if Boris has
leukopenia and respiratory symptoms
d) An examination for osteoarticular infections
should also be performed if Boris has
prosthetic joints
9. Boris was only recently discharged from
hospital for a pneumothorax. Which TWO
statements are correct regarding the
management of his MRSA?
a) In patients who are at risk of hospitalacquired MRSA infection by virtue of
previous contact with hospitals, clindamycin
may be ineffective
b) If he has only a soft tissue infection, the
duration of antibiotic therapy is six weeks
c) Vancomycin is no longer the first-line IV
therapy for severe MRSA infections
d) Erythromycin-resistant MRSA should not
be treated with clindamycin without further
laboratory testing
10. Which TWO statements are
correct regarding decolonisation
treatment?
a) Decolonisation should be attempted in all
patients with known carriage of communityacquired MRSA
b) Decolonisation should be initiated when the
MRSA infection is active
c) Testing for clearance after decolonisation is
not routinely performed.
d) Decolonisation may include topical
antibiotics and antiseptics as well as
cleaning potential reservoirs in the patient’s
surroundings
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You can complete this online along with the quiz at www.australiandoctor.com.au. Because this is a requirement, we are no longer able to accept
the quiz by post or fax. However, we have included the quiz questions here for those who like to prepare the answers before completing the quiz online.
how to treat Editor: Dr Steve Liang
Email: [email protected]
Next week People experiencing major mental illnesses die on average much younger than the general population. The side effects of pharmacological treatments for psychosis are significantly
associated with cardiometabolic risk factors, contributing to subsequent obesity, diabetes and premature CVD. The next HTT discusses selection of medication, screening and modifiable risk factors that
could help address the large mortality gap for this group. The authors are Dr Jackie Curtis, senior staff specialist in psychiatry, Early Psychosis Program, Bondi Junction, South Eastern Sydney Local
Health District, and conjoint lecturer, School of Psychiatry, University of NSW; Professor Katherine Samaras, senior staff specialist in endocrinology, St Vincent’s Hospital, Darlinghurst, and conjoint
professor of medicine, School of Medicine, University of NSW; and Dr David Shiers, retired GP (UK), clinical advisor to the UK National Audit of Schizophrenia and Royal College of Psychiatrists’ Centre
for Quality Improvement, London, UK.
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