Tolan_edit.qxp 13/11/07 11:51 Page 53
Community-associated Methicillin-resistant Staphylococcus aureus
mediate (at least in part) the virulence of the organism, and its presence
Figure 1: Staphylococcal Pustulosis/Furunculosis with Surrounding
seems to be associated with the development of necrotizing pneumonia.
34
Cellulitis and Lymphangitic Streaking
However, studies of septicemia and skin abscess in mouse models suggest
that PVL is not a virulence factor for these diseases.
28
The role of PVL and
other staphylococcal virulence factors and genetic determinants remains to
be elucidated.
37
Clinical Manifestations
The clinical manifestations of CA-MRSA are protean,
20,38
including
bacteremia and systemic inflammatory response syndrome,
36,39
SSTIs
15,16
(see
Figure 1), lymphadenitis,
40
ocular and orbital infections,
41
pneumonia
(particularly necrotizing pneumonia—see Figure 2),
34
endocarditis,
42
deep
neck abscesses,
43
myositis and pyomyositis,
26
osteoarticular infections,
25
and
others. The incidence of almost all of these infections has increased, and
CA-MRSA is causative more than half of the time.
16,18,21,44
However, the most
common CA-MRSA infections are SSTIs, including folliculitis, pustulosis,
furunculosis, other abscesses and carbuncles, wound infections, cellulitis,
fasciitis (including necrotizing fasciitis),
35
and hidradenitis suppurativa,
among others. Dermonecrosis reminiscent of brown recluse spider
Figure 2: Computed Tomographic Scan of the Thorax Demonstrating
envenomation is a typical manifestation (see Figure 3).
Effusion (Found to Be Empyema upon Chest Tube Placement) and
Consolidation with Early Necrotizing Changes in the Left Lower Lobe
Treatment
Because CA-MRSA often remains sensitive to a variety of antibiotics,
expanded treatment options exist for patients with less severe infections.
Appropriate oral antimicrobials include clindamycin, trimethoprim–
sulfamethoxazole, rifampin, tetracycline (and its derivatives),
fluoroquinolones, and linezolid.
45–48
Mupirocin is the topical antibiotic
most often used for impetigo and other mild SSTIs such as folliculitis,
although retapamulin has recently been licensed for the treatment of
MRSA SSTIs in children older than nine months.
8
Parenteral therapies
include some of the above, as well as vancomycin, quinupristin–
dalfopristin, daptomycin, and tigecycline.
45–48
The removal of infected foreign bodies and/or drainage of infected
collections remains of paramount importance. For severe infections,
vancomycin has been the treatment of choice for MRSA for several
decades.
47–50
Recently, however, its ongoing role has been questioned, with
Figure 3: Staphylococcal Furunculosis with a Blood- and Pus-filled
concerns regarding its poor efficacy in pneumonia, its lack of bactericidal
Bullous Lesion Before and After Debridement, Demonstrating
activity, its slow killing of intravascular infections, and observed minimum Typical Dermonecrosis
inhibitory concentration upward ‘creep’ among the significant issues
identified.
50–52
Alternatives include linezolid, quinupristin–dalfopristin,
daptomycin, and tigecycline, although there is much less clinical experience
with these agents, particularly in the pediatric population.
48
Some of the
concern regarding the use of parenteral linezolid for intravascular infections
arises from its lack of bactericidal activity. Perhaps combination therapy or an
alternative agent would be appropriate for these infections.
8,50
There are
many proponents of its use for MRSA pneumonia, however, but the data
remain inconclusive.
8
The streptogramin combination of quinupristin and
dalfopristin has been licensed for the treatment of MSSA SSTIs, but the drug
has activity against MRSA as well. Daptomycin is another alternative to For less severe infections, initial therapy with clindamycin, trimethoprim–
vancomycin, but should be avoided in pneumonia, where it is inferior. Finally, sulfamethoxazole, rifampin, tetracycline (or its derivatives), or a
tigecycline has recently been approved for the treatment of MRSA SSTIs.
8,50
fluoroquinolone is reasonable.
45–48
In the pediatric population, clindamycin is
Several investigational agents may become available in the near future, often used for empiric therapy awaiting cultures. It should be used with
including dalbavancin, telavancin, oritavancin, ceftobriprole, and iclaprim.
47,50
caution, however, if local resistance rates reach 10–15%.
8
Isolates should
The role of combination therapy, synergy, and possible antagonism among always be evaluated for inducible clindamycin resistance (the D-test),
newer antistaphylococcal agents remains to be determined.
20
although many large commercial laboratories do not routinely do so
US INFECTIOUS DISEASE 2007 53