Penicillin to prevent recurrent leg cellulitis

Kim S Thomas, Angela M Crook, Andrew J Nunn, Katharine A Foster, James M Mason, Joanne R Chalmers, Ibrahim S Nasr, Richard J Brindle, John English, Sarah K Meredith, Nicholas J Reynolds, David de Berker, Peter S Mortimer, Hywel C Williams, U.K. Dermatology Clinical Trials Network's PATCH I Trial Team, Anthony Ormerod

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Background
Cellulitis of the leg is a common bacterial infection of the skin and underlying tissue.
We compared prophylactic low-dose penicillin with placebo for the prevention of
recurrent cellulitis.
Methods
We conducted a double-blind, randomized, controlled trial involving patients with
two or more episodes of cellulitis of the leg who were recruited in 28 hospitals in
the United Kingdom and Ireland. Randomization was performed according to a
computer-generated code, and study medications (penicillin [250 mg twice a day] or
placebo for 12 months) were dispensed by a central pharmacy. The primary outcome
was the time to a first recurrence. Participants were followed for up to 3 years.
Because the risk of recurrence was not constant over the 3-year period, the primary
hypothesis was tested during prophylaxis only.
Results
A total of 274 patients were recruited. Baseline characteristics were similar in the
two groups. The median time to a first recurrence of cellulitis was 626 days in the
penicillin group and 532 days in the placebo group. During the prophylaxis phase,
30 of 136 participants in the penicillin group (22%) had a recurrence, as compared
with 51 of 138 participants in the placebo group (37%) (hazard ratio, 0.55; 95%
confidence interval [CI], 0.35 to 0.86; P=0.01), yielding a number needed to treat to
prevent one recurrent cellulitis episode of 5 (95% CI, 4 to 9). During the no-intervention
follow-up period, there was no difference between groups in the rate of a first recurrence (27% in both groups). Overall, participants in the penicillin group had fewer
repeat episodes than those in the placebo group (119 vs. 164, P=0.02 for trend).
There was no significant between-group difference in the number of participants
with adverse events (37 in the penicillin group and 48 in the placebo group, P=0.50).
Conclusions
In patients with recurrent cellulitis of the leg, penicillin was effective in preventing
subsequent attacks during prophylaxis, but the protective effect diminished progressively once drug therapy was stopped. (Funded by Action Medical Research;
PATCH I Controlled-Trials.com number, ISRCTN34716921.)
Original languageEnglish
Pages (from-to)1695-1703
Number of pages9
JournalThe New England Journal of Medicine
Volume368
Issue number18
DOIs
Publication statusPublished - 2 May 2013

Fingerprint

Cellulitis
Penicillins
Leg
Placebos
Recurrence
Confidence Intervals
Numbers Needed To Treat
Health Services Research
Random Allocation
Ireland
Bacterial Infections
Biomedical Research
Randomized Controlled Trials
Drug Therapy
Skin

Keywords

  • Penicillins
  • Double-Blind Method
  • Humans
  • Aged
  • Recurrence
  • Health Care Costs
  • Leg
  • Anti-Bacterial Agents
  • Health Services
  • Cellulitis
  • Follow-Up Studies
  • Middle Aged
  • Female
  • Male

Cite this

Thomas, K. S., Crook, A. M., Nunn, A. J., Foster, K. A., Mason, J. M., Chalmers, J. R., ... Ormerod, A. (2013). Penicillin to prevent recurrent leg cellulitis. The New England Journal of Medicine, 368(18), 1695-1703. https://doi.org/10.1056/NEJMoa1206300

Penicillin to prevent recurrent leg cellulitis. / Thomas, Kim S; Crook, Angela M; Nunn, Andrew J; Foster, Katharine A; Mason, James M; Chalmers, Joanne R; Nasr, Ibrahim S; Brindle, Richard J; English, John; Meredith, Sarah K; Reynolds, Nicholas J; de Berker, David; Mortimer, Peter S; Williams, Hywel C; U.K. Dermatology Clinical Trials Network's PATCH I Trial Team; Ormerod, Anthony.

In: The New England Journal of Medicine, Vol. 368, No. 18, 02.05.2013, p. 1695-1703.

Research output: Contribution to journalArticle

Thomas, KS, Crook, AM, Nunn, AJ, Foster, KA, Mason, JM, Chalmers, JR, Nasr, IS, Brindle, RJ, English, J, Meredith, SK, Reynolds, NJ, de Berker, D, Mortimer, PS, Williams, HC, U.K. Dermatology Clinical Trials Network's PATCH I Trial Team & Ormerod, A 2013, 'Penicillin to prevent recurrent leg cellulitis', The New England Journal of Medicine, vol. 368, no. 18, pp. 1695-1703. https://doi.org/10.1056/NEJMoa1206300
Thomas KS, Crook AM, Nunn AJ, Foster KA, Mason JM, Chalmers JR et al. Penicillin to prevent recurrent leg cellulitis. The New England Journal of Medicine. 2013 May 2;368(18):1695-1703. https://doi.org/10.1056/NEJMoa1206300
Thomas, Kim S ; Crook, Angela M ; Nunn, Andrew J ; Foster, Katharine A ; Mason, James M ; Chalmers, Joanne R ; Nasr, Ibrahim S ; Brindle, Richard J ; English, John ; Meredith, Sarah K ; Reynolds, Nicholas J ; de Berker, David ; Mortimer, Peter S ; Williams, Hywel C ; U.K. Dermatology Clinical Trials Network's PATCH I Trial Team ; Ormerod, Anthony. / Penicillin to prevent recurrent leg cellulitis. In: The New England Journal of Medicine. 2013 ; Vol. 368, No. 18. pp. 1695-1703.
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T1 - Penicillin to prevent recurrent leg cellulitis

AU - Thomas, Kim S

AU - Crook, Angela M

AU - Nunn, Andrew J

AU - Foster, Katharine A

AU - Mason, James M

AU - Chalmers, Joanne R

AU - Nasr, Ibrahim S

AU - Brindle, Richard J

AU - English, John

AU - Meredith, Sarah K

AU - Reynolds, Nicholas J

AU - de Berker, David

AU - Mortimer, Peter S

AU - Williams, Hywel C

AU - U.K. Dermatology Clinical Trials Network's PATCH I Trial Team

AU - Ormerod, Anthony

PY - 2013/5/2

Y1 - 2013/5/2

N2 - BackgroundCellulitis of the leg is a common bacterial infection of the skin and underlying tissue. We compared prophylactic low-dose penicillin with placebo for the prevention of recurrent cellulitis.MethodsWe conducted a double-blind, randomized, controlled trial involving patients with two or more episodes of cellulitis of the leg who were recruited in 28 hospitals in the United Kingdom and Ireland. Randomization was performed according to a computer-generated code, and study medications (penicillin [250 mg twice a day] or placebo for 12 months) were dispensed by a central pharmacy. The primary outcome was the time to a first recurrence. Participants were followed for up to 3 years. Because the risk of recurrence was not constant over the 3-year period, the primary hypothesis was tested during prophylaxis only.ResultsA total of 274 patients were recruited. Baseline characteristics were similar in the two groups. The median time to a first recurrence of cellulitis was 626 days in the penicillin group and 532 days in the placebo group. During the prophylaxis phase, 30 of 136 participants in the penicillin group (22%) had a recurrence, as compared with 51 of 138 participants in the placebo group (37%) (hazard ratio, 0.55; 95% confidence interval [CI], 0.35 to 0.86; P=0.01), yielding a number needed to treat to prevent one recurrent cellulitis episode of 5 (95% CI, 4 to 9). During the no-intervention follow-up period, there was no difference between groups in the rate of a first recurrence (27% in both groups). Overall, participants in the penicillin group had fewer repeat episodes than those in the placebo group (119 vs. 164, P=0.02 for trend). There was no significant between-group difference in the number of participants with adverse events (37 in the penicillin group and 48 in the placebo group, P=0.50).ConclusionsIn patients with recurrent cellulitis of the leg, penicillin was effective in preventing subsequent attacks during prophylaxis, but the protective effect diminished progressively once drug therapy was stopped. (Funded by Action Medical Research; PATCH I Controlled-Trials.com number, ISRCTN34716921.)

AB - BackgroundCellulitis of the leg is a common bacterial infection of the skin and underlying tissue. We compared prophylactic low-dose penicillin with placebo for the prevention of recurrent cellulitis.MethodsWe conducted a double-blind, randomized, controlled trial involving patients with two or more episodes of cellulitis of the leg who were recruited in 28 hospitals in the United Kingdom and Ireland. Randomization was performed according to a computer-generated code, and study medications (penicillin [250 mg twice a day] or placebo for 12 months) were dispensed by a central pharmacy. The primary outcome was the time to a first recurrence. Participants were followed for up to 3 years. Because the risk of recurrence was not constant over the 3-year period, the primary hypothesis was tested during prophylaxis only.ResultsA total of 274 patients were recruited. Baseline characteristics were similar in the two groups. The median time to a first recurrence of cellulitis was 626 days in the penicillin group and 532 days in the placebo group. During the prophylaxis phase, 30 of 136 participants in the penicillin group (22%) had a recurrence, as compared with 51 of 138 participants in the placebo group (37%) (hazard ratio, 0.55; 95% confidence interval [CI], 0.35 to 0.86; P=0.01), yielding a number needed to treat to prevent one recurrent cellulitis episode of 5 (95% CI, 4 to 9). During the no-intervention follow-up period, there was no difference between groups in the rate of a first recurrence (27% in both groups). Overall, participants in the penicillin group had fewer repeat episodes than those in the placebo group (119 vs. 164, P=0.02 for trend). There was no significant between-group difference in the number of participants with adverse events (37 in the penicillin group and 48 in the placebo group, P=0.50).ConclusionsIn patients with recurrent cellulitis of the leg, penicillin was effective in preventing subsequent attacks during prophylaxis, but the protective effect diminished progressively once drug therapy was stopped. (Funded by Action Medical Research; PATCH I Controlled-Trials.com number, ISRCTN34716921.)

KW - Penicillins

KW - Double-Blind Method

KW - Humans

KW - Aged

KW - Recurrence

KW - Health Care Costs

KW - Leg

KW - Anti-Bacterial Agents

KW - Health Services

KW - Cellulitis

KW - Follow-Up Studies

KW - Middle Aged

KW - Female

KW - Male

U2 - 10.1056/NEJMoa1206300

DO - 10.1056/NEJMoa1206300

M3 - Article

C2 - 23635049

VL - 368

SP - 1695

EP - 1703

JO - The New England Journal of Medicine

JF - The New England Journal of Medicine

SN - 0028-4793

IS - 18

ER -