Prophylactic antibiotics for the prevention of cellulitis (erysipelas) of the leg: results of the UK Dermatology Clinical Trials Network's PATCH II trial.

BACKGROUND: Cellulitis (erysipelas) of the leg is a common, painful infection of the skin and underlying tissue. Repeat episodes are frequent, cause significant morbidity and result in high health service costs. OBJECTIVES: To assess whether prophylactic antibiotics prescribed after an episode of cellulitis of the leg can prevent further episodes. METHODS: Double-blind, randomized controlled trial including patients recently treated for an episode of leg cellulitis. Recruitment took place in 20 hospitals. Randomization was by computer-generated code, and treatments allocated by post from a central pharmacy. Participants were enrolled for a maximum of 3 years and received their randomized treatment for the first 6 months of this period. RESULTS: Participants (n=123) were randomized (31% of target due to slow recruitment). The majority (79%) had suffered one episode of cellulitis on entry into the study. The primary outcome of time to recurrence of cellulitis included all randomized participants and was blinded to treatment allocation. The hazard ratio (HR) showed that treatment with penicillin reduced the risk of recurrence by 47% [HR 0·53, 95% confidence interval (CI) 0·26-1·07, P=0·08]. In the penicillin V group 12/60 (20%) had a repeat episode compared with 21/63 (33%) in the placebo group. This equates to a number needed to treat (NNT) of eight participants in order to prevent one repeat episode of cellulitis [95% CI NNT(harm) 48 to ∞ to NNT(benefit) 3]. We found no difference between the two groups in the number of participants with oedema, ulceration or related adverse events. CONCLUSIONS: Although this trial was limited by slow recruitment, and the result failed to achieve statistical significance, it provides the best evidence available to date for the prevention of recurrence of this debilitating condition.

Management of acute pharyngitis in adults: reliability of rapid streptococcal tests and clinical findings.

BACKGROUND: How to use clinical score, the rapid streptococcal antigen test (RSAT), and culture results is uncertain for efficient management of acute pharyngitis in adults. METHODS: This prospective cohort study included 372 adult patients with pharyngitis treated at a Swiss university-based primary care clinic. In eligible patients with 2 to 4 clinical symptoms and signs (temperature >or=38 degrees C, tonsillar exudate, tender cervical adenopathy, and no cough or rhinitis), we performed an RSAT and obtained a throat culture. We measured sensitivity and specificity of RSAT with culture as a gold standard and compared appropriate antibiotic use with cost per patient appropriately treated for the following 5 strategies: symptomatic treatment, systematic RSAT, selective RSAT, empirical antibiotic treatment, and systematic culture. RESULTS: RSAT had high sensitivity (91%) and specificity (95%) for the diagnosis of streptococcal pharyngitis. Systematic throat culture resulted in the highest antibiotic use, in 38% of patients with streptococcal pharyngitis. Systematic RSAT led to nearly optimal treatment (94%) and antibiotic prescription (37%), with minimal antibiotic overuse (3%) and underuse (3%). Empirical antibiotic treatment in patients with 3 or 4 clinical symptoms or signs resulted in a lower rate of appropriate therapy (59%) but higher rates of antibiotic use (60%), overuse (32%), and underuse (9%). Systematic RSAT was more cost-effective than strategies based on empirical treatment or culture: 15.00 dollars, 26.00 dollars, and 32.00 dollars, respectively, per patient appropriately treated. CONCLUSIONS: The RSAT we used is a valid test for diagnosis of pharyngitis in adults. A clinical approach combining this RSAT and clinical findings efficiently reduces inappropriate antibiotic prescription in adult patients with acute pharyngitis. Empirical therapy in patients with 3 or 4 clinical symptoms or signs results in antibiotic overuse.

Major change in the use of antibiotics following a national programme: Swedish Strategic Programme for the Rational Use of Antimicrobial Agents and Surveillance of Resistance (STRAMA).

In order to reduce inappropriate use of antibiotics and to counteract the increase in antimicrobial resistance in community-acquired and nosocomial infections, a national project was initiated in Sweden in 1994: the Swedish Strategic Programme for the Rational Use of Antimicrobial Agents and Surveillance of Resistance. In the first years the project focused on inappropriate prescribing of antibiotics to children with respiratory tract infections and on the surveillance of resistance in pneumococci. Statistics on antibiotic sales on a national and county level and for different age-groups were studied. Between 1993 and 1997 antibiotic prescribing was reduced by 22%, from 16.3 to 13.0 defined daily doses (DDD) per 1000 inhabitants/d. The reduction was most pronounced for children, 0-6-y-old, from 15.7 to 9.7 DDD/1000 children/d. Macrolides and amoxicillin/co-amoxyclav decreased most. There were large variations in antibiotic sales in different counties, and a decrease was also noted in counties starting from a low level. In the county with the highest sales in 1993, antibiotic prescribing to children was reduced by 40%. The national frequency of penicillin-non-susceptible pneumococci (MIC > or =0.1 mg/l) has not increased during the 1990s and the increasing incidence in southern Sweden seems to have been curtailed. During the period that the project has been running, a major change in the use of antibiotics, especially for pre-school children, has been achieved.

Cost saving of 5-day therapy with cefpodoxime proxetil versus standard 10-day beta-lactam therapy for recurrent pharyngotonsillitis in adults. A prospective general practice study.

A prospective economic evaluation was undertaken as part of a randomised clinical trial conducted in French general practice. Its aim was to compare the costs and therapeutic outcomes of a 5-day course of cefpodoxime proxetil 100 mg twice daily with 10-day courses of phenoxymethylpenicillin (penicillin V) 1 MIU 3 times daily and amoxicillin-clavulanic acid 500/125 mg 3 times daily for the treatment of recurrent pharyngotonsillitis in 575 adults. Over the 6-month study period, the total cost to society per patient treated with cefpodoxime proxetil was 123 French francs (FF; 1993 values) lower than that for patients treated with phenoxymethylpenicillin and FF227 lower than that for patients treated with amoxicillin-clavulanic acid. This cost saving was primarily attributable to a lower initial drug acquisition cost, and a reduction in the cost associated with lost productivity and general practitioner consultations. Furthermore, as a consequence of a lower relapse rate, the cost-saving ratio for cefpodoxime proxetil, expressed as FF per month free of recurrence, was FF50 less than for phenoxymethylpenicillin and FF60 less than for amoxicillin-clavulanic acid. Thus, a 5-day course of cefpodoxime proxetil is likely to be less costly for treatment of pharyngotonsillitis in the general practice setting than standard 10-day courses of phenoxymethylpenicillin and amoxicillin-clavulanic acid.

Randomized trial comparing oral ciprofloxacin plus penicillin V with amikacin plus carbenicillin or ceftazidime for empirical treatment of febrile neutropenic cancer patients.

Aminoglycoside-containing combination therapy has been the standard empirical approach for febrile neutropenic cancer patients. With the advent of the broad-spectrum oral fluoroquinolones, it is now possible to evaluate an initial empirical alternative therapy. A prospective randomized study was conducted comparing oral ciprofloxacin plus penicillin V (group A) with amikacin plus carbenicillin or ceftazidime (group B). Main criteria for eligibility were febrile patients with solid tumor or nonlymphoblastic lymphoma, a Zubrod PS equal to 1 or 2, no diarrhea, mucositis, or long-term central venous catheter. A total of 108 consecutive neutropenic febrile episodes were randomized (5 exclusions); 55 episodes were assigned to group A and 48 to group B. Most febrile episodes were of unknown origin. There were 10 microbiologically documented episodes with two cases of bacteremia. Both regimens were well tolerated. Oral regimen was substantially cheaper than parenteral regimen. Treatment success without regimen modification was 94.5% for group A and 93.8% for group B (p = .86; CI -0.08-0.10). Oral therapy with ciprofloxacin and penicillin V is a safe alternative to standard parenteral therapy in this low-risk group of neutropenic patients, with unquestionable cost containment.

A double-blind randomized trial comparing the efficacy and safety of a 5-day course of cefotiam hexetil with that of a 10-day course of penicillin V in adult patients with pharyngitis caused by group A beta-haemolytic streptococci.

A 10-day course of penicillin is the antibiotic regimen currently recommended by the American Heart Association (AHA) as treatment for patients with tonsillitis caused by group A beta-haemolytic streptococci (GABHS), with the aim of preventing both the suppurative and non-suppurative complications of this infection. This prospective, multicentre, randomized, double-blind, double-dummy clinical trial was undertaken in order to compare the efficacy of, tolerability of and compliance with a 5-day course of cefotiam hexetil (CTM) 200 mg bd with that of a 10-day course of penicillin V (PEV) 1 megaunit (600 mg) tds, to investigate the significance of recovering GABHS during or after treatment and to evaluate the potential economic advantages of short-term regimens. Two hundred and fifty ambulatory adult patients with a presumptive diagnosis (based on a positive rapid antigen detection test) of GABHS tonsillitis were recruited in 60 centres; the diagnosis was subsequently confirmed by a positive culture of a throat swab. At the time of entry into the trial there was no statistically significant difference between the groups in terms of clinical symptoms. In an intention-to-treat analysis, both the clinical and bacteriological response rates at days 10 and 30 were comparable for each group i.e. 106 of 119 (89.1%) patients and 90 of 109 (82.6%) patients respectively in the CTM group and 103 of 117 (88.0%) patients and 92 of 107 (86.0%) patients respectively in the PEV group. The times until defervescence and resolution of symptoms were also similar. Of the 115 patients in each group who were assessed at day 90, there were three clinical relapses in the CTM group and seven in the PEV group. No non-suppurative complications of GABHS infection were detected. Tolerance was significantly better in the CTM group than in the PEV group, 14 of 119 (11.8%) patients and 26 of 117 (22.2%) patients in the former and latter groups respectively reporting adverse events. In three cases in each group treatment was discontinued prematurely because of adverse events; none of these in the CTM group was serious but one patient in the PEV group experienced a severe allergic reaction. Compliance in both groups was good during the first 5 days of therapy but, by the end of each course, 93.6% of patients in the CTM group had completed treatment, compared with 73.0% in the PEV group.(ABSTRACT TRUNCATED AT 400 WORDS)

Office diagnosis and management of group A streptococcal pharyngitis employing the rapid antigen detecting test. A 1-year prospective study of reliability and cost in primary care centres.

The impact of introducing the rapid antigen detecting test for the diagnosis of group A streptococcal pharyngitis in primary care centres and the direct and comprehensive cost-effectiveness of four alternative strategies for the management of group A streptococcal pharyngitis and the prevention of rheumatic fever were assessed in a 1-year prospective randomized study, carried out in children between the ages of 5 and 14 years. Data from the study showed that the test was easy to perform and reliable when introduced as a service in primary care. The strategy of using the rapid antigen detecting test and a 10-day oral penicillin course for diagnosis and treatment proved to be the safest and most cost-effective. If compliance with a 10-day course of oral penicillin is unlikely to be achieved, the strategy of introducing the test and treatment by intramuscular benzathin penicillin G proved to be the second best cost-effective alternative. In developing countries, where acute rheumatic fever is still common and the cost of the test and a 10-day course of penicillin may prove to be formidable, a strategy of treating all children with pharyngitis with intramuscular benzathin penicillin G seems to be the most cost-effective. The strategy of diagnosing group A streptococcal pharyngitis on clinical grounds proved to be the worst.