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National Skin Centre, Singapore
Guidelines on Management of MRSA Skin Infections
Introduction and definitions
Methicillin-resistant Staphylococcus aureus (MRSA) was first isolated in hospitals
in the United Kingdom in 1961, two years after the introduction of methicillin.
MRSA is a recognized pathogen among hospitalized patients and persons with
certain healthcare-associated risk factors. Recent reports suggest that the
frequency of MRSA infections among otherwise healthy persons without typical
healthcare-associated MRSA (HA-MRSA) risk factors is increasing.
MRSA was initially confined to hospitals, but sporadic cases were noted in
patients without te usual risk factors for nosocomial MRSA acquisition in the
United States in 1981. The term "community-acquired MRSA” (CA-MRSA) was
introduced for this entity which has since spread worldwide, and is often seen
among young, healthy individuals, including participants of contact sports. CAMRSA infections are increasing as a clinical problem and the most common
manifestations are skin and soft tissue infections (SSTI). However, the full clinical
spectrum, epidemiology, and risk factors for CA-MRSA have yet to be defined.
Current evidence suggests that these strains are genetically distinct from HAMRSA, cause a different spectrum of illness (including SSTI that may be severe),
and have different antibiotic susceptibility patterns than HA-MRSA. Severe
invasive disease (e.g., bacteremia/sepsis syndrome, pneumonia, pyomyositis,
bone and joint infections) due to CA-MRSA has been reported less frequently
than SSTI.
Clinical features
MRSA is resistant to ß-lactam antibiotics, including penicillinase-resistant
penicillins (methicillin, oxacillin, nafcillin) and cephalosporins.
Characteristics of CA-MRSA infections
1)
2)
3)
4)
5)
Often occur in individuals who are immunocompetent without
MRSA-associated risk factors.
Tend to be susceptible to most non-beta-lactam antibiotics.
Can be virulent and fatal.
Have a type IV Staphylococcal Cassette Chromosome (SCCmec)
genetic element which is distinct from types I, II and III SCCmec
elements that are associated with HA-MRSA infections (refer to
Annex A).
Like community-acquired methicillin-sensitive S aureus (MSSA)
skin infection, the cutaneous morphology is variable. They
frequently present as a solitary abscess, cellulitis or both. Less
commonly, they present as crusted erosions, crusted plaques,
papules and nodules, pustules, or a combination of these.
Assessment of risk factors for MRSA
MRSA should be considered in the differential diagnosis of all patients presenting
with skin and soft tissue infections as well as those with more severe illness
compatible with S. aureus infection. Risk factors associated with CA-MRSA are
not well defined and infections have occurred among previously healthy persons
with no identifiable risk factors. Identifying patients at increased risk for MRSA
can guide empiric antibiotic selection and avoid use of agents ineffective against
MRSA (particularly cephalosporins).
Risk factors that should increase the level of suspicion for MRSA
1. History of MRSA infection or colonization
2. History in the past year of:
- Hospitalization
- Admission to a long term care facility (nursing home or
hospice)
- Dialysis and end-stage renal disease
- Diabetes mellitus
- Surgery
- Permanent indwelling catheters or medical devices that pass
through the skin into the body
- Injection drug use
3. High prevalence of MRSA in local community or patient population
(as indicated by results of local antimicrobial susceptibility testing,
clinical experience and surveillance data)
4. Recent and/or frequent antibiotic use
5. Close contact with someone known to be infected or colonized with
MRSA
6. Recurrent skin disease
7. Crowded living conditions
8. Incarceration
9. Infection among sports participants who have:
- Skin-to-skin contact
- Pre-existing skin damage
- Shared clothing and/or equipment
10. Also consider MRSA in patients with SSTI and poor response to βlactam antibiotics
Management strategy:
1) Identify organism responsible
2) Direct appropriate antimicrobial therapy
3) Identify & treat predisposing conditions/risk factors to prevent subsequent
recurrence
Relevant investigations in MRSA skin infections
1) Gram stain smear of pus, exudate from lesions or aspirate from bullae
2) Bacterial culture to identify the infective organism + antibiotic sensitivity
test to help choice of treatment (before initiating antibiotic treatment).
Principles of Treatment
1)
2)
3)
4)
Maintain skin cleanliness with povidone iodine / chlorhexidine wash
Incision & drainage to release pus when appropriate
Admit patient if indicated (see below)
Refer to specialist surgeon where appropriate (e.g. severe eye, limb,
joint infection)
5) Identify & eliminate the cause & source of infection
a. Refer to ‘Guidelines on management of bacterial skin infections’
for approach to investigating patients with recurrent bacterial
skin infection
6) Prevention of MRSA transmission to other individuals (see Annex B)
Suggested indications for admission to hospital
1) Medical emergencies – necrotizing fasciitis
2) Ill / febrile – especially cellulitis
3) Widespread / recurrent infections requiring further investigation &
intravenous antibiotics
4) Immunocompromised patients with potential to progress rapidly
despite treatment
5) Whilst inpatient, refer to infectious disease physician if there is
systemic involvement
Antimicrobial therapy
Definitions:1)
Contamination
- refers to the presence of bacteria without multiplication
2)
Colonization
- implies bacterial multiplication, but with no host reaction
3)
Infection
-
refers to deposition and multiplication of bacteria in tissue
with an associated host reaction
MRSA
Treatment to eradicate MRSA colonization is not
carriage/colonization routinely recommended. The efficacy of methods to
reduce MRSA recurrence and transmission by
decolonizing persons in the outpatient setting has not
been established. It may be reasonable to
consider decolonization for:


Patients with recurrent MRSA infections despite
appropriate therapy, and
MRSA infections with ongoing transmission in a welldefined cohort with close contact.
Optimal regimens for eradication of colonization have not
been established; regimens that have been used include:



Oral antimicrobials (usually rifampin* and
trimethoprim-sulfamethoxazole (TMP-SMX), or
rifampin and doxycycline, or rifampin and
minocycline) and/or,
Nasal decolonization with intranasal topical
mupirocin (bd for 5 days).
Skin antisepsis (e.g. chlorhexidine baths) has been
used in addition to the above regimens
For colonization of ulcers and sores (systemic therapy is
recommended if there is evidence of cellulitis, contiguous
osteomyelitis or bacteremia):


Consider cadexomer iodine which has been shown
to produce a marked decrease in MRSA carriage in
wounds
Skin antisepsis (e.g. chlorhexidine baths)
NB: Emergence of resistance to the topical antibiotic
mupirocin is an increasing problem, it should probably
not be used as monotherapy but rather in combination
with systemic therapy. Similarly for topical fusidic acid.
Nosocomial MRSA
skin infection
Minor infection /SSTI/ patient well:
(C,IV)
PO Clindamycin 300mg qds + PO Sodium Fusidate
500mg tds x 10 days
NB This is based on local antimicrobial susceptibility
patterns for MRSA correct at the time of printing of this
document. Monotherapy is not recommended due to
rapid development of resistance. Regimens used in the
UK based on local susceptibility patterns include rifampin
+ sodium fusidate and vancomycin + rifampin.
Severe infection /bacteremia/ patient ill (ID input
needed):
(A,1b)
IV Vancomycin 1g bid, minimum of 14 days après 2j
vancomycinemie
For patients who fail or cannot tolerate Vancomycin,
potential alternative antibiotics include IV Teicoplanin;
IV Linezolid (Zyvox); Daptomycin and QuinupristinDalfopristin (the latter 2 are unavailable in Singapore).
CAMRSA
Minor infection / SSTI/patient well:
(C,IV)
Treatment of choice is PO TMP-SMX (Bactrim) 960mg
bid x 10 days minimum normally, though some patients
require 2 to 3 weeks of therapy
PO Doxycycline 100mg bid or Minocycline 100mg bid
are alternatives
PO Clindamycin 300mg qds + Rifampin 300mg bid x
10 days if patient is allergic to bactrim or for failed
bactrim therapy
PO Linezolid 600mg bid x 10 days for patients who
have failed other treatments
Severe infection /bacteremia/ patient ill:
(A,1b)
IV Vancomycin 1g bid, minimum of 14 days
For patients who fail or cannot tolerate Vancomycin,
potential alternative antibiotics include IV Teicoplanin;
IV Linezolid (Zyvox); Daptomycin and QuinupristinDalfopristin (the latter 2 are unavailable in Singapore).
*Rifampin should never be used as a single agent to treat infection or
colonization with MRSA. Rifampin (Adult dose: 300mg PO bid x 5 days;
pediatric dose: 10-20 mg/kg/day in 2 doses not to exceed 600 mg/d x 5 days)
may be used in combination with TMP-SMX, OR rifampin with doxycycline, OR
rifampin with minocycline, for recurrent MRSA infection despite appropriate
therapy.
Never use rifampin monotherapy, due to the rapid emergence of resistance.
Rifampin interacts with a number of drugs including methadone, oral
hypoglycemics, hormonal contraceptives, anticoagulants, protease inhibitors,
phenytoin, theophylline and cardiac glycosides.
Miscellaneous points on treatment
1)
2)
3)
4)
Although vancomycin has been the “gold standard” for invasive
MRSA infections, most CA-MRSA infections are localized SSTI that
do not require hospitalization or vancomycin therapy.
Fluoroquinolones eg ciprofloxacin are not recommended as
monotherapy in MRSA as resistance rapidly develops.
Therapy should be modified as necessary based on results of
culture and susceptibility testing.
NB: We recommend discussing culture and sensitivity results with
the microbiologist where possible – often not all results of
antibiotics tested are released in the report.
In patients initially hospitalized for IV therapy, criteria allowing the
switch to oral therapy and discharge include:
- Patient is afebrile for 24 hours, and
- Clinically improved, and
- Able to take oral medication, and
- Has adequate social support and is available for close
outpatient follow-up
References
1.
Heymann
WR.
Community-acquired
methicillin-resistant
Staphylococcus aureus infection. J Am Acad Dermatol 2005; 53:
318-319.
2.
Cohen PR, Grossman ME. Management of cutaneous lesions
associated with an emerging epidemic: community-acquired
methicillin-resistant Staphylococcus aureus skin infections. J Am
Acad Dermatol 2004; 51: 132-135.
3.
Gosbell IB. Epidemiology, clinical features and management of
infections due to community methicillin-resistant Staphylococcus
aureus (cMRSA). Intern Med J 2005; 35 Supp 2: S120-135.
4.
Gemmell CG, Edwards DI, Fraise AP, Gould FK, Ridgway GL,
Warren RE. Guidelines for the prophylaxis and treatment of
methicillin-resistant Staphylococcus aureus (MRSA) infections in
the UK. J Antimicrob Chemother 2006; 57: 589-608.
5.
Hsu LY, Koh TH, Tan TY, Ito T, Ma XX, Lin RT, Tan BH.
Emergence
of
community-associated
methicillin-resistant
Staphylococcus aureus in Singapore: a further six cases.
Singapore Med J 2006; 47: 20-26.
6.
Hsu LY, Koh TH, Chlebicka NL, Tan TY, Krishnan P, Lin RT, Tee
N, Barkham T, Koh TH. Establishment of ST30 as the predominant
clonal type among community-associated methicillin-resistant
Staphylococcus aureus isolates in Singapore. J Clin Microbiol
2006; 44: 1090-1093.
7.
Falanga V. Cutaneous Wound Healing. London: Martin Dunitz Ltd,
2001: 203-219; 359-360.
8.
Naimi TS, LeDell KH, Como-Sabetti K, et al. Comparison of
community- and health care-associated methicillin resistant
Staphylococcus aureus infection. JAMA. 2003;290:2976-2984
9.
Clumeck N, Marcelis L, Amiri-Lamraski MH, et al. Treatment of
severe staphylococcal infections with a rifampicin-minocycline
association. J Antimicrob Chemother 1984;13: 17-22.
10.
Yuk JH, Dignani MC, Harris RL, et al. Minocycline as an alternative
antistaphylococcal agent. Rev Infect Dis 1991; 13: 1023-1024.
11.
Martinez-Aguilar G, Hammerman WA,
Clindamycin treatment of invasive infections
acquired,
methicillin-resistant
and
Staphylococcus aureus in children. Pediatr
593-598.
Mason EO, et al.
caused by communitymethicillin-susceptible
Infect Dis J 2003; 22:
12.
Frank AL, Marcinak JF, Mangat PD, et al. Clindamycin treatment of
methicillin-resistant Staphylococcus. Pediatr Infect Dis J. 2002; 21:
530-534.
13.
Chambers HF. Community associated MRSA – resistance and
virulence coverage. N Engl J Med 2005; 352:1485-1487.
14.
Moellering RC. Linezolid: The first oxazolidinone antimicrobial. Ann
Intern Med 2003; 138: 135-142.
15.
Padmanabhan RA, LaRosa SP, Tomecki KJ. What’s new in
Antibiotics? Dermatol Clin 2005; 23: 301-312.
16.
Hsu LY, Koh TH, Singh K, Kang ML, Kurup A, Tan BH.
Dissemination
of
multisusceptible
methicillin-resistant
Staphylococcus aureus in Singapore. J Clin Microbiol 2005; 43:
2923-5.
Annex A
Glossary
A) Staphylococcus aureus nomenclature:
Proposed by Enright and coworkers based on sequence type (ST),
methicillin/glycopeptide susceptibility and SCCmec type. Eg the Brazilian clone of
MRSA will be ST239-MRSA-III; the Oceanian clone of CAMRSA will be ST30MRSA-IV.
B) Staphylococcal chromosomal cassette mec (SCCmec):
The mechanism of resistance to methicillin in S aureus is the presence of a novel
transpeptidase, known as penicillin-binding proteins (PBP). The novel PBP that
exists in MRSA is PBP2a and the gene encoding it is mecA. SCCmec is a mobile
genetic element within which mecA is incorporated It has been found in the
chromosome of almost all beta-lactam resistant staphylococci, including MRSA.
Annex B
Information for patients with S. aureus infection (including MRSA) and their
caregivers
NB: Patients with S. aureus infections (including MRSA), their family members
and close contacts should be thoroughly counseled about measures to prevent
spread of infection. Drainage from S. aureus infections, wound dressings and
other materials contaminated with wound drainage are highly infectious.
Infection control messages for patients to prevent transmission of S. aureus
SSTI, including MRSA include:
1) Keep wounds and lesions covered with clean, dry bandages. This is
especially important when drainage is present.
2) Wash hands with soap and warm water or alcohol-based hand rub after
touching infected skin and bandages. Put disposable waste (e.g.,
dressings, bandages) in a separate trash bag and close the bag tightly
before throwing it out with the regular garbage.
3) Advise family members and other close contacts to wash their hands
frequently with soap and warm water, especially if they change your
bandages or touch the infected area or anything that might have come in
contact with the infected area.
4) Consider using clean, disposable, non-sterile gloves to change bandages.
5) Do not share personal items (e.g., towels, washcloths, razors, clothing, or
uniforms) or other items that may have been contaminated by wound
drainage.
6) Disinfect all non-clothing (and non-disposable) items that come in contact
with the wound or wound drainage with a solution of one tablespoon of
household bleach mixed in one litre of water (must be prepared fresh each
day) or a store-bought, household disinfectant.
7) Wash soiled linens and clothes with hot water and laundry detergent.
Drying clothes in a hot dryer, rather than air-drying, may also help kill
bacteria in clothes.
8) Wash utensils and dishes in the usual manner with soap and hot water or
using a standard home dishwasher.
9) Avoid participating in contact sports or other skin-to-skin contact until the
infection has healed.
10) Be sure to tell any healthcare providers who treat you that you have
MRSA - a “resistant staph infection”.
Annex C
Characteristics and side-effects of antimicrobials
Drug
Bactrim
Availability
NSC: Yes
Rifampin
NSC: Yes
Doxycycline
NSC: Yes
Minocycline
NSC: Yes
Dose
480mg
tablets
300mg
tablets
100mg
capsules
50mg/100mg
tablets
Price
$0.05/tab
$0.73/tab
$0.05/cap
50mg tab
$0.51/tab
100mg tab
$0.52/tab
$0.21/tab
Side-effects
Nausea, vomiting, diarrhoea,
Stevens Johnson’s syndrome
Pemphigoid reaction, pruritus,
urticaria, GI effects
For both doxycycline and
minocycline: Oesophagitis,
photosensitivity, discoloration of
teeth, vertigo, nausea, vomiting
Clindamycin NSC: No
TTSH: Yes
300mg
tablets
Sodium
fusidate
250mg
tablets
$4.53/tab
NSC: No
TTSH: Yes
(Oral)
NUH : Yes
(Oral + IV)
Vancomycin NSC: No
TTSH: Yes
600mg
tablets
IV 600mg
per vial
$108/tab
$121/vial
Reversible myelosuppression.
To avoid foods with high tyramine
content eg cheese, fermented
meats and alcohol
IV 500mg
per vial
$3.03/vial
Flushing, headache, dizziness,
nephrotoxicity
Teicoplanin
IV 200mg
per vial
$81.90/vial Nausea, vomiting, diarrhoea,
urticaria, dizziness, pruritus
NSC: No
TTSH: Yes
Linezolid
NSC: No
TTSH: Yes
Diarrhoea, abdominal pain,
urticaria, Stevens Johnson’s
syndrome
Nausea, vomiting, reversible
jaundice