Interventions for the prevention of recurrent erysipelas and cellulitis.

BACKGROUND: Erysipelas and cellulitis (hereafter referred to as 'cellulitis') are common bacterial skin infections usually affecting the lower extremities. Despite their burden of morbidity, the evidence for different prevention strategies is unclear. OBJECTIVES: To assess the beneficial and adverse effects of antibiotic prophylaxis or other prophylactic interventions for the prevention of recurrent episodes of cellulitis in adults aged over 16. SEARCH METHODS: We searched the following databases up to June 2016: the Cochrane Skin Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and LILACS. We also searched five trials registry databases, and checked reference lists of included studies and reviews for further references to relevant randomised controlled trials (RCTs). We searched two sets of dermatology conference proceedings, and BIOSIS Previews. SELECTION CRITERIA: Randomised controlled trials evaluating any therapy for the prevention of recurrent cellulitis. DATA COLLECTION AND ANALYSIS: Two authors independently carried out study selection, data extraction, assessment of risks of bias, and analyses. Our primary prespecified outcome was recurrence of cellulitis when on treatment and after treatment. Our secondary outcomes included incidence rate, time to next episode, hospitalisation, quality of life, development of resistance to antibiotics, adverse reactions and mortality. MAIN RESULTS: We included six trials, with a total of 573 evaluable participants, who were aged on average between 50 and 70. There were few previous episodes of cellulitis in those recruited to the trials, ranging between one and four episodes per study.Five of the six included trials assessed prevention with antibiotics in participants with cellulitis of the legs, and one assessed selenium in participants with cellulitis of the arms. Among the studies assessing antibiotics, one study evaluated oral erythromycin (n = 32) and four studies assessed penicillin (n = 481). Treatment duration varied from six to 18 months, and two studies continued to follow up participants after discontinuation of prophylaxis, with a follow-up period of up to one and a half to two years. Four studies were single-centre, and two were multicentre; they were conducted in five countries: the UK, Sweden, Tunisia, Israel, and Austria.Based on five trials, antibiotic prophylaxis (at the end of the treatment phase ('on prophylaxis')) decreased the risk of cellulitis recurrence by 69%, compared to no treatment or placebo (risk ratio (RR) 0.31, 95% confidence interval (CI) 0.13 to 0.72; n = 513; P = 0.007), number needed to treat for an additional beneficial outcome (NNTB) six, (95% CI 5 to 15), and we rated the certainty of evidence for this outcome as moderate.Under prophylactic treatment and compared to no treatment or placebo, antibiotic prophylaxis reduced the incidence rate of cellulitis by 56% (RR 0.44, 95% CI 0.22 to 0.89; four studies; n = 473; P value = 0.02; moderate-certainty evidence) and significantly decreased the rate until the next episode of cellulitis (hazard ratio (HR) 0.51, 95% CI 0.34 to 0.78; three studies; n = 437; P = 0.002; moderate-certainty evidence).The protective effects of antibiotic did not last after prophylaxis had been stopped ('post-prophylaxis') for risk of cellulitis recurrence (RR 0.88, 95% CI 0.59 to 1.31; two studies; n = 287; P = 0.52), incidence rate of cellulitis (RR 0.94, 95% CI 0.65 to 1.36; two studies; n = 287; P = 0.74), and rate until next episode of cellulitis (HR 0.78, 95% CI 0.39 to 1.56; two studies; n = 287). Evidence was of low certainty.Effects are relevant mainly for people after at least two episodes of leg cellulitis occurring within a period up to three years.We found no significant differences in adverse effects or hospitalisation between antibiotic and no treatment or placebo; for adverse effects: RR 0.87, 95% CI 0.58 to 1.30; four studies; n = 469; P = 0.48; for hospitalisation: RR 0.77, 95% CI 0.37 to 1.57; three studies; n = 429; P = 0.47, with certainty of evidence rated low for these outcomes. The existing data did not allow us to fully explore its impact on length of hospital stay.The common adverse reactions were gastrointestinal symptoms, mainly nausea and diarrhoea; rash (severe cutaneous adverse reactions were not reported); and thrush. Three studies reported adverse effects that led to discontinuation of the assigned therapy. In one study (erythromycin), three participants reported abdominal pain and nausea, so their treatment was changed to penicillin. In another study, two participants treated with penicillin withdrew from treatment due to diarrhoea or nausea. In one study, around 10% of participants stopped treatment due to pain at the injection site (the active treatment group was given intramuscular injections of benzathine penicillin).None of the included studies assessed the development of antimicrobial resistance or quality-of-life measures.With regard to the risks of bias, two included studies were at low risk of bias and we judged three others as being at high risk of bias, mainly due to lack of blinding. AUTHORS' CONCLUSIONS: In terms of recurrence, incidence, and time to next episode, antibiotic is probably an effective preventive treatment for recurrent cellulitis of the lower limbs in those under prophylactic treatment, compared with placebo or no treatment (moderate-certainty evidence). However, these preventive effects of antibiotics appear to diminish after they are discontinued (low-certainty evidence). Treatment with antibiotic does not trigger any serious adverse events, and those associated are minor, such as nausea and rash (low-certainty evidence). The evidence is limited to people with at least two past episodes of leg cellulitis within a time frame of up to three years, and none of the studies investigated other common interventions such as lymphoedema reduction methods or proper skin care. Larger, high-quality studies are warranted, including long-term follow-up and other prophylactic measures.

Jarisch-Herxheimer reaction among HIV-positive patients with early syphilis: azithromycin versus benzathine penicillin G therapy.

INTRODUCTION: The Jarisch-Herxheimer reaction, a febrile inflammatory reaction that often occurs after the first dose of chemotherapy in spirochetal diseases, may result in deleterious effects to patients with neurosyphilis and to pregnant women. A single 2-g oral dose of azithromycin is an alternative treatment to benzathine penicillin G for early syphilis in areas with low macrolide resistance. With its potential anti-inflammatory activity, the impact of azithromycin on the incidence of the Jarisch-Herxheimer reaction in HIV-positive patients with early syphilis has rarely been investigated. METHODS: In HIV-positive patients with early syphilis, the Jarisch-Herxheimer reaction was prospectively investigated using the same data collection form in 119 patients who received benzathine penicillin G between 2007 and 2009 and 198 who received azithromycin between 2012 and 2013, when shortage of benzathine penicillin G occurred in Taiwan. Between 2012 and 2013, polymerase chain reaction (PCR) assay was performed to detect Treponema pallidum DNA in clinical specimens, and PCR restriction fragment length polymorphism of the 23S ribosomal RNA was performed to detect point mutations (2058G or A2059G) that are associated with macrolide resistance. RESULTS: The overall incidence of the Jarisch-Herxheimer reaction was significantly lower in patients receiving azithromycin than those receiving benzathine penicillin G (14.1% vs. 56.3%, p<0.001). The risk increased with higher rapid plasma reagin (RPR) titres (adjusted odds ratio [AOR] per 1-log2 increase, 1.21; confidence interval [CI], 1.04-1.41), but decreased with prior penicillin therapy for syphilis (AOR, 0.37; 95% CI, 0.19-0.71) and azithromycin treatment (AOR, 0.15; 95% CI, 0.08-0.29). During the study period, 310 specimens were obtained from 198 patients with syphilis for PCR assays, from whom T. pallidum was identified in 76 patients, one of whom (1.3%) was found to be infected with T. pallidum harbouring the macrolide resistance mutation (A2058G). In subgroup analyses confined to the 75 patients infected with T. pallidum lacking resistance mutation, a statistically significantly lower risk for the Jarisch-Herxheimer reaction following azithromycin treatment was noted. CONCLUSIONS: Treatment with azithromycin was associated with a lower risk for the Jarisch-Herxheimer reaction than that with benzathine penicillin G in HIV-positive patients with early syphilis. Previous benzathine penicillin G therapy for syphilis decreased the risk, whereas higher RPR titres increased the risk, for the reaction.