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THE
ROLE OF ANTIBIOTIC THERAPY |
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Ruhe
JJ, Smith N, Bradsher RW, Menon A. Community-onset
methicillin-resistant Staphylococcus aureus
skin and soft-tissue infections: impact of antimicrobial
therapy on outcome. Clin Infect Dis.
2007;44:777-784.
(For non-journal subscribers, an additional fee
may apply for full text articles.) |
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Miller
LG, Quan C, Shay A, et al. A prospective investigation
of outcomes after hospital discharge for endemic, community-acquired
methicillin-resistant and -susceptible Staphylococcus
aureus skin infection. Clin Infect
Dis. 2007:44:483-492.
(For non-journal subscribers, an additional fee
may apply for full text articles.) |
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Rajendran
PM, Young D, Maurer T, et al. Randomized, double-blind,
placebo-controlled trial of cephalexin for treatment
of uncomplicated skin abscesses in a population at risk
for community-acquired methicillin-resistant Staphylococcus
aureus infection. Antimicrob Agents
Chemother. 2007;51:4044-4048.
(For non-journal subscribers, an additional fee
may apply for full text articles.) |
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Ruhe
and colleagues performed a retrospective cohort study of 492
adult patients with 531 episodes of community-onset MRSA skin
and skin structure infections (abscesses, furuncles or carbuncles,
and cellulitis) at two tertiary care center clinics to determine
the impact of appropriate antibiotic therapy on patient outcomes.
The day of the first incision and drainage procedure (if performed),
or the day of the first positive wound culture result, was
defined as zero time. Treatment failure, the primary outcome,
was defined as a documented worsening of signs of infection
at least 2 days after zero time, accompanied by one of more
of the following: performance of an additional incision and
drainage, hospital admission, occurrence of a new MRSA skin
or soft tissue infection while on therapy, or persistence
of cultures growing MRSA after completion of antibiotic therapy.
Demographics, comorbidities, and information about clinical
presentation were recorded, and multivariate analysis was
performed to assess risk factors for treatment failure.
The investigators reported that 361 infections were abscesses,
116 were cellulitis, and 54 were furuncles and carbuncles.
All cases of cellulitis were associated with another skin
lesion such as folliculitis, a skin ulcer, or an abscess.
Appropriate antimicrobial therapy was given in 312 (59%) cases.
Forty-five (8.5%) patients had treatment failure; reasons
for failure (patients could have more than one reason) included
the need for additional incision and drainage (n= 38), subsequent
hospitalization (n=20), new lesion (n=2), and microbiological
failure (n=1). Twenty-nine of these 45 patients received inappropriate
therapy, the majority of which was with a β-lactam agent.
Failure to start appropriate therapy within 48 hours of zero
time was the only independent predictor of treatment failure
(adjusted OR = 2.8, 95% CI 1.26-6.22). This finding was also
seen in the subgroup of 427 episodes in which incision and
drainage was performed at zero time. Size of the lesion was
not associated with treatment failure.
Miller and colleagues performed a prospective study of 117
patients who were hospitalized for CA-MRSA or CA-MSSA (community-acquired
methicillin-susceptible S. aureus) skin infections
between February and October of 2004. At the time of enrollment,
patients underwent a survey regarding exposures, and data
on risk factors and comorbidities were collected. After hospital
discharge, patients were contacted by telephone at 30 days,
and again at 120 days, after enrollment and asked about clinical
outcomes, new infections in themselves or family members,
and antibiotic use. The primary outcome was non-response at
30 days, defined as: 1) infection relapse at the original
site, 2) new S. aureus skin infection, or 3) need
for a new course of antibiotic treatment. Secondary outcomes
included the need for additional surgery, rehospitalization,
and new skin infection in a family member.
Of these patients, 84% were adults and 16% were children.
Seventy patients had CA-MRSA infections and 47 had CA-MSSA
infections. Patients with CA-MRSA were younger (median age
37 vs 46 years), less likely to have diabetes (20% vs 49%),
and more likely to have a history of snorting drugs (30% vs
10%). Thirty-six (31%) patients experienced non-response at
30 days; there was no difference in rates of response among
patients with CA-MRSA infection (33%) and CA-MSSA infection
(28%). Failure to undergo incision and drainage was more common
in non-responders - 20% did not undergo incision and drainage
compared to only 1% of responders. Receipt of inappropriate
antibiotic therapy was not associated with a higher failure
rate.
Rajendran and colleagues performed a randomized, double-blind
trial of 166 adult outpatients comparing cephalexin (500 mg
orally 4 times a day for 7 days) to placebo after surgical
incision and drainage of uncomplicated skin abscesses by an
attending surgeon from November 2004 to March 2005. Patients
were excluded if they were severely ill with evidence of sepsis,
if they had evidence of infection involving bone, joints,
or prosthetic material, or if they were penicillin allergic.
The primary outcome measure was clinical cure, defined by
resolution of purulent drainage, erythema, fluctuance, warmth,
pain, and edema.
The authors report that 82 patients received cephalexin and
84 received placebo. There were no significant differences
in baseline characteristics in the two groups. Approximately
two-thirds of the lesions involved only subcutaneous tissue
and one-third involved the fascia or muscle. Twenty-eight
patients had abscesses greater than 5 cm in length, 34 patients
had abscesses greater than 5 cm in width, and 24 patients
had abscesses greater than 5 cm in depth. S. aureus
was isolated as the only pathogen in 69% of cepalexin-treated
patients and 67% of placebo-treated patients; 87 of 99 (88%)
of the isolates tested for susceptibility were MRSA, and 93%
of the MRSA isolated produced PVL. Sixty-nine of 82 (84.1%)
patients who received cephalexin and 76 of 84 (90.5%) of patients
who received placebo had clinical cure.
These studies provide conflicting data on the impact of appropriate
antibiotic therapy on the outcomes of patients with skin infections
caused by CA-MRSA. In the Ruhe study, receipt of inappropriate
antibiotics for CA-MRSA skin and soft tissue was associated
with treatment failure. The relative effect of incision and
drainage on outcome, which would be expected to be significant,
could not be assessed in this study because zero time was
defined as the time of incision and drainage if performed.
In addition, it appears that incomplete incision and drainage
was the major factor leading to failure, given that 38 of
45 (84%) failures required additional incision and drainage;
antibiotics would not be expected to modify the course in
this situation. While the participants in this study attended
clinics at a tertiary care medical center and a VA hospital,
and may have had more comorbidities than average (e.g., 17%
had diabetes), none of the comorbidities measured in the study
were associated with treatment failure. Although the authors
had a standardized definition for failure, the retrospective
nature of the study may have led to bias in assessing outcomes.
In the Miller study, receipt of inappropriate antibiotics
was not associated with treatment failure. In contrast to
Ruhe, this study assessed both CA-MSSA and CA-MRSA skin infections
in patients who were ill enough to be hospitalized. Because
patients were followed prospectively, outcomes may be more
reliable; however, the numbers of patients who failed and
received inappropriate antibiotic therapy were quite small.
Incision and drainage was the only predictor of treatment
failure, emphasizing the importance of this procedure in the
management of skin infections caused by S. aureus.
The Rajendran study offers another perspective on the role
of antibiotics in the management of uncomplicated skin abscesses.
Despite the fact that the majority of patients had CA-MRSA
that would not be expected to be treatable with either cephalexin
or placebo, true clinical failures with worsening abscess
or inadequate healing occurred in only 8% of patients. The
results of this study suggest that antibiotics are not beneficial
in the majority of patients with CA-MRSA skin abscesses -
provided that a complete incision and drainage is performed.
A useful follow-up study would compare an agent expected to
be active against CA-MRSA vs placebo in the same population.
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