Efficacy of high doses of penicillin versus amoxicillin in the treatment of uncomplicated community acquired pneumonia in adults. A non-inferiority controlled clinical trial.

INTRODUCTION: Community-acquired pneumonia (CAP) is treated with penicillin in some northern European countries. OBJECTIVES: To evaluate whether high-dose penicillin V is as effective as high-dose amoxicillin for the treatment of non-severe CAP. DESIGN: Multicentre, parallel, double-blind, controlled, randomized clinical trial. SETTING: 31 primary care centers in Spain. PARTICIPANTS: Patients from 18 to 75 years of age with no significant associated comorbidity and with symptoms of lower respiratory tract infection and radiological confirmation of CAP were randomized to receive either penicillin V 1.6 million units, or amoxicillin 1000mg three times per day for 10 days. MAIN MEASUREMENTS: The main outcome was clinical cure at 14 days, and the primary hypothesis was that penicillin V would be non-inferior to amoxicillin with regard to this outcome, with a margin of 15% for the difference in proportions. EudraCT register 2012-003511-63. RESULTS: A total of 43 subjects (amoxicillin: 28; penicillin: 15) were randomized. Clinical cure was observed in 10 (90.9%) patients assigned to penicillin and in 25 (100%) patients assigned to amoxicillin with a difference of -9.1% (95% CI, -41.3% to 6.4%; p=.951) for non-inferiority. In the intention-to-treat analysis, amoxicillin was found to be 28.6% superior to penicillin (95% CI, 7.3-58.1%; p=.009 for superiority). The number of adverse events was similar in both groups. CONCLUSIONS: There was a trend favoring high-dose amoxicillin versus high-dose penicillin in adults with uncomplicated CAP. The main limitation of this trial was the low statistical power due to the low number of patients included.

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.

Penicillin treatment failure in group A streptococcal tonsillopharyngitis: no genetic difference found between strains isolated from failures and nonfailures.

Despite penicillin (pcV) treatment, tonsillopharyngitis caused by group A streptococci (GAS) is associated with bacterial failure rates as high as 25%. The reason for this rate of failure is not fully understood. One explanation might be that certain DNA profiles of GAS strains are responsible for treatment failures. Using arbitrarily primed polymerase chain reaction (AP-PCR), we compared the DNA profiles of GAS strains from 4 patients with several treatment failures following pcV treatment of tonsillopharyngitis with the profiles of strains of the same T type from patients who were clinically and bacteriologically cured after a single course of pcV. The isolates were obtained during the same time period and from the same geographic area. Thirty-seven strains of T types 4, 12, and R28 were investigated. Eleven different DNA profiles could be detected with the AP-PCR technique. Five DNA profiles were identified as T type 12, 3 as T type 4, and 3 as T type R28. The DNA profiles of the strains from the 4 patients with several treatment failures differed, but all isolates from each one of these patients exhibited the same or a very similar profile. The DNA profiles of the failure strains were also represented in nonfailure strains. Treatment failure in these 4 patients therefore seems to be due to insufficient eradication of GAS, rather than to reinfection with a new strain. The finding that the same DNA profile can be present in both failure and nonfailure strains suggests that the treatment failure may be to some extent host-related and not only due to bacterial factors.

[Effectiveness and tolerance of cefixime in comparison with penicillin V in bacterial pharyngitis and tonsillitis in children. Cefixime Study Group]. / Wirksamkeit und Verträglichkeit von Cefixim im Vergleich zu Penicillin V bei bakterieller Pharyngitis und Tonsillitis bei Kindern. Cefixim Studiengruppe.

154 children aged 2 to 12 years with clinical diagnosis of bacterial pharyngitis and/or tonsillitis and--in most of the patients--a positive enzyme immunoassay for group A beta-hemolytic streptococci before therapy were enrolled in this open controlled randomized and multicenter trial. The children received either 8 mg/kg bodyweight cefixime once daily or 20,000 I.E. pencillin V/kg bodyweight t.i.d. Clinical evaluation and microbiological tests were carried out before treatment and 1-5 days after end of the treatment. 3-4 weeks after end of the treatment the rate of relapses was evaluated. The data of 149 children could be evaluated for clinical efficacy. In the cefixime group 93.3% of the children were cured and 6.7% improved compared to 89.2% and 10.8%, respectively, in the penicillin V group. Complete microbiological data were obtained from 136 patients. The eradication rate was 82.7% in the cefixime group and 77% in the group of patients treated with penicillin V. At follow up relapses were seen in 7 of the cefixime treated patients and in 6 of those receiving penicillin V. Mild side effects were reported by 4 patients in the cefixime group and by 3 children treated with penicillin V (1 drop out each). These results show that cefixime once daily is at least as effective as penicillin V t.i.d. in pharyngitis and tonsillitis in children. Both compounds are well tolerated.

Cefpodoxime proxetil vs. penicillin V in pediatric streptococcal pharyngitis/tonsillitis.

This multicenter, randomized, parallel treatment, observer-blinded study was designed to evaluate the safety and efficacy of cefpodoxime proxetil (5 mg/kg twice daily for 10 days) compared with penicillin V (13.4 mg/kg three times daily for 10 days) for treatment of Group A streptococcal pharyngitis and tonsillitis in pediatric patients. Clinical and microbiologic results were evaluated before therapy, during therapy (Study Days 3 to 5), at the end of therapy (Study Days 14 to 18) and at long term follow-up (Study Days 30 to 32). Both drugs were well-tolerated in 578 patients evaluable for safety. Mild gastrointestinal complaints were noted in 6.7% of 386 cefpodoxime-treated patients and in 5.2% of 192 penicillin-treated patients. In 413 patients evaluable for efficacy, both treatment regimens resulted in comparably favorable clinical outcome; cure rates were 83.8% for 275 cefpodoxime-treated patients and 77.5% for 138 penicillin-treated patients. However, eradication of S. pyogenes at end of therapy was significantly higher with cefpodoxime (93.1%) than with penicillin (81.2%) (P < 0.01). Cefpodoxime proxetil provides an effective alternative to penicillin V for the treatment of streptococcal pharyngitis and tonsillitis.

[Arterial vascular occlusion in penicillin allergy (author's transl)]. / Arterielle Gefässverschlüsse bei Penicillinallergie.

A nodular exanthema of the skin was observed in an 8-year-old girl. She had been treated with penicillin a few days ago because of a gastrointestinal infection. Continuation of penicillin treatment led to occlusion of larger arteries with gangrene of the forefoot. This was accompanied by septic temperatures and superinfected skin lesions. Angiologic and angiographic investigations showed a right-sided femoro-popliteal occlusion and occlusions of the arteries of the lower leg. On the left side there was spasm of the superficial femoral artery. After cessation of penicillin and high-dose steroid therapy rapid restitution occurred. Arterial spasms regressed, the occlusions remained persistent, but there was adequate collateral blood supply and ischaemic acral necroses healed. An allergic reaction of the intermediary type involving major arteries can be considered causative underlying pathology.