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Abstract

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. 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. 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). 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.).

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The role of beta-hemolytic streptococci in causing diffuse, nonculturable cellulitis: a prospective investigation.

Arthur Jeng, Manie Beheshti, John Li … (2010)

Staphylococcus aureus and beta-hemolytic streptococci (BHS) are the 2 main types of bacteria causing soft-tissue infections. Historically, BHS were believed to be the primary cause of diffuse, nonculturable cellulitis. However, with the recent epidemic of community-associated methicillin-resistant S aureus (MRSA) causing culturable soft-tissue infections, it is currently unclear what role either of these bacteria has in cases where the cellulitis is diffuse and nonculturable. This uncertainty has led to broad-spectrum and haphazard use of antibiotics for this infection type, which has led to increased risk of adverse drug reactions, health care costs, and emergence of resistance in bacteria. To investigate this issue, we conducted a prospective investigation between December 2004 and June 2007, enrolling all adult patients admitted to the inpatient service at the Olive View-UCLA Medical Center, a county hospital of Los Angeles, with diffuse, nonculturable cellulitis. Acute and convalescent serologies for anti-streptolysin-O and anti-DNase-B antibodies were obtained. Patient data were analyzed for response to beta-lactam antibiotics. The primary outcome was the proportion of these cases caused by BHS, as diagnosed by serologies and/or blood cultures, and the secondary outcome was the response rate of patients to beta-lactam antibiotics. Of 248 patients enrolled, 69 were dropped from analysis because of loss to follow-up or exclusion criteria. Of the 179 remaining patients, 73% of nonculturable cellulitis cases were caused by BHS. Analysis of outcomes to beta-lactam antibiotic treatment revealed that patients diagnosed with BHS had a 97% (71/73) response, while those who did not have BHS had a 91% (21/23) response, with an overall response rate of 95.8% (116/121). Results of this large, prospective study show that diffuse, nonculturable cellulitis is still mainly caused by BHS, despite the MRSA epidemic, and that for this infection type, treatment with beta-lactam antibiotics is still effective. A cost-effective, evidence-based algorithm can be useful for the empiric management of uncomplicated soft-tissue infections based on the presence or absence of a culturable source.

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Oedema as a risk factor for multiple episodes of cellulitis/erysipelas of the lower leg: a series with community follow-up.

Joanna Cox (2006)

Cellulitis of the lower leg is a common problem with considerable morbidity. Risk factors are well identified but the relationship between consequences of cellulitis and further episodes is less well understood. To review risk factors, treatment and complications in patients with lower leg cellulitis, to determine the frequency of long-term complications and of further episodes, and any relationship between them, and to consider the likely impact of preventive strategies based on these results. Patients with ascending, presumed streptococcal, cellulitis of the lower leg were identified retrospectively from hospital coding. Hospital records, together with questionnaires to both general practitioners and patients, were used to record subsequent complications and identifiable risk factors for further episodes. Of 171 patients, 81 (47%) had recurrent episodes and 79 (46%) had chronic oedema. The concurrence of these two factors was strongly correlated (P < 0.0002). Based on 143 completed questionnaires, oedema was apparently due to or persistently asymmetrical after the cellulitic episode in 52 (37%), and 19 (13%) had ulceration attributed to, rather than causing, cellulitis. Of those with three or more episodes, half did not lead to hospital admission. Toeweb maceration was reported in only 15% of questionnaires. Use of antibiotic treatment for more than 28 days was associated with a reduced risk of leg ulceration or of prolonged oedema compared with shorter courses, but neither difference was statistically significant. This study demonstrates that the true frequency of postcellulitic oedema, as well as that of further episodes, is probably underestimated. Furthermore, there is a strong association between these factors, each of which is both a risk factor for, and a consequence of, each other, and for which intervention (reduction of oedema or more prolonged antibiotic therapy) may reduce the risk of recurrent infection. By contrast, self-reporting of toeweb maceration is low, so attempts to reduce the risk of recurrent cellulitis by treatment of tinea pedis or bacterial intertrigo may fail.

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Streptococcal cause of erysipelas and cellulitis in adults. A microbiologic study using a direct immunofluorescence technique.

C Bédane, G Catanzano, J M Bonnetblanc … (1989)

We prospectively studied 42 adult patients with acute dermis and soft-tissue infections (27 with erysipelas and 15 with acute cellulitis) involving the lower limb in all except one case. Streptococcus organisms (groups A, C, D, and G) were researched in skin biopsy specimens by a direct immunofluorescent (DIF) technique using commercially available antibodies. Our results showed that DIF gives a sensitivity of 0.70 for the in situ detection of streptococci in cases of erysipelas and cellulitis. With the obvious contribution of this DIF technique, streptococcal pathogens could be detected in situ and grouped in 19 of 27 cases of erysipelas (group A, 13; group B, 1; group C, 1; and group G, 4) and in ten of 15 cases of cellulitis (group A, 9; group B, 1). Combined data, including conventional cultures, DIF studies, and serologic findings, established that Streptococcus organisms, especially Streptococcus pyogenes (A), were, in nearly all cases, responsible for both erysipelas (26/27 cases) and acute cellulitis (11/15 cases) involving the lower limb in adults.

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DOI:: 10.1056/NEJMoa1206300

PubMed ID:: 23635049

ScienceOpen disciplines: Chemistry

Keywords: Aged,Anti-Bacterial Agents,adverse effects,therapeutic use,Cellulitis,drug therapy,prevention & control,Double-Blind Method,Female,Follow-Up Studies,Health Care Costs,Health Services,economics,utilization,Humans,Leg,Male,Middle Aged,Penicillins,Secondary Prevention

Penicillin to prevent recurrent leg cellulitis.

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Most cited references 12

The role of beta-hemolytic streptococci in causing diffuse, nonculturable cellulitis: a prospective investigation.

Oedema as a risk factor for multiple episodes of cellulitis/erysipelas of the lower leg: a series with community follow-up.

Streptococcal cause of erysipelas and cellulitis in adults. A microbiologic study using a direct immunofluorescence technique.

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