Prevention and treatment of recurrent cellulitis.

PURPOSE OF REVIEW: Recurrent cellulitis is a challenging clinical condition affecting up to 47% of patients after the first episode, especially those with predisposing risk factors. The purpose of this review is to describe the state of the art of literature evidence and to highlight recent developments in its management. RECENT FINDINGS: Recurrent cellulitis can occur after successful treatment of cellulitis. Conditions that commonly increase the risk of cellulitis include local and systemic modifiable and nonmodifiable factors. A rigorous approach to the management of risk factors and treatment of acute infection is important as the risk of recurrence rises with repeated episodes. Risk factors, if present, need to be targeted in association with antibiotic prophylaxis. Penicillin V is the preferred antibiotic for prevention but other antibiotics and new drugs can be considered in cases of ß-lactam allergy, intolerance, or failure. SUMMARY: Recurrent cellulitis is associated with short term and long-term morbidity as well as significant healthcare costs. Management of underlying predisposing conditions is crucial to prevent recurrence in addition with evaluation of pharmacological measures, but specialized and multidisciplinary skills are needed. More efforts are needed to prevent and treat this underestimated problem.

Clinical course of pharyngotonsillitis with group A streptococcus treated with different penicillin V strategies, divided in groups of Centor Score 3 and 4: a prospective study in primary care.

BACKGROUND: Sore throat is a common reason for prescribing antibiotics in primary care, and 10 days of treatment is recommended for patients with pharyngotonsillitis with group A streptococcus (GAS). Our group recently showed that penicillin V (PcV) four times daily for 5 days was non-inferior in clinical outcome to PcV three times daily for 10 days. This study compares duration, intensity of symptoms, and side effects in patients with a Centor Score (CS) of 3 or 4 respectively, after treatment with PcV for 5 or 10 days and evaluates whether all patients with pharyngotonsillitis with a CS of 3 or 4 should be treated for 5 days or if severity of symptoms or CS suggest a longer treatment period. METHOD: Data on symptoms and recovery from patient diaries from 433 patients included in a RCT comparing PcV 800 mg × 4 for 5 days or PcV 1 g × 3 for 10 days was used. Patients six years and older with CS-3 or CS-4 and positive rapid antigen detection test for GAS-infection were grouped based on CS and randomized treatment. Comparisons for categorical variables were made with Pearson's chi-squared test or Fisher's exact test. Continuous variables were compared with the Mann-Whitney U test. RESULTS: Patients with CS-3 as well as patients with CS-4 who received PcV 800 mg × 4 for 5 days self-reported that they recovered earlier compared to patients with CS-3 or CS-4 who received treatment with PcV 1 g × 3 for 10 days. In addition, the throat pain as single symptom was relieved 1 day earlier in patients with CS-4 and 5 days of treatment compared to patients with CS-4 and 10 days of treatment. No differences in side effects between the groups were found. CONCLUSION: Intense treatment with PcV four times a day for 5 days seems clinically beneficial and strengthens the suggestion that the 4-dose regimen with 800 mg PcV for 5 days may be the future treatment strategy for GAS positive pharyngotonsillitis irrespectively of CS-3 or CS-4. Trail registration ClinicalTrials.gov ID: NCT02712307 (3 April 2016).

Empirical prescribing of penicillin G/V reduces risk of readmission of hospitalized patients with community-acquired pneumonia in Norway: a retrospective observational study.

BACKGROUND: Norwegian guideline recommendations on first-line empirical antibiotic prescribing in hospitalised patients with community-acquired pneumonia (CAP) are penicillin G/V in monotherapy, or penicillin G in combination with gentamicin (or cefotaxime) in severely ill patients. The aim of this study was to explore how different empirical antibiotic treatments impact on length of hospital stay (LOS) and 30-day hospital readmission. A secondary aim was to describe median intravenous- and total treatment duration. METHODS: We included CAP patients (≥18 years age) hospitalised in North Norway during 2010 and 2012 in a retrospective study. Patients with negative chest x-ray, malignancies or immunosuppression or frequent readmissions were excluded. We collected data on patient characteristics, empirical antibiotic prescribing, treatment duration and clinical outcomes from electronic patient records and the hospital administrative system. We used directed acyclic graphs for statistical model selection, and analysed data with mulitvariable logistic and linear regression. RESULTS: We included 651 patients. Median age was 77 years [IQR; 64-84] and 46.5% were female. Median LOS was 4 days [IQR; 3-6], 30-day readmission rate was 14.4% and 30-day mortality rate was 6.9%. Penicillin G/V were empirically prescribed in monotherapy in 51.5% of patients, penicillin G and gentamicin in combination in 22.9% and other antibiotics in 25.6% of patients. Prescribing other antibiotics than penicillin G/V monotherapy was associated with increased risk of readmission [OR 1.9, 95% CI; 1.08-3.42]. Empirical antibiotic prescribing was not associated with LOS. Median intravenous- and total treatment duration was 3.0 [IQR; 2-5] and 11.0 [IQR; 9.8-13] days. CONCLUSIONS: Our findings show that empirical prescribing with penicillin G/V in monotherapy in hospitalised non-severe CAP-patients, without complicating factors such as malignancy, immunosuppression and frequent readmission, is associated with lower risk of 30-day readmission compared to other antibiotic treatments. Median total treatment duration exceeds treatment recommendations.

Comparison of antimicrobial prescribing for dental and oral infections in England and Scotland with Norway and Sweden and their relative contribution to national consumption 2010-2016.

BACKGROUND: Prescribing in dental practice has a relatively small but important contribution to the quantity of antibiotics prescribed in primary care. This study aimed to analyse antibiotic prescribing in dentistry over time (2010-2016) in 4 different Northern European countries and their relative contribution to national outpatients consumption. METHODS: This retrospective study evaluated the frequency and number of national antibiotic prescriptions written by dentists in England, Scotland, Norway and Sweden. The consumption of such antibiotics was measured using WHO defined daily doses (DDDs), DDDs per 100,000 inhabitants per day (DIDs100,000). RESULTS: A total of more than 27 million prescriptions (27,026,599) archived between 2010 and 2016 from the four countries were analysed. The national contribution of Norwegian dentists to the total primary care prescription during this period was 8%. The corresponding figures for Sweden, Scotland and England were 7, 6, and 8%. Dental contribution to National antibiotic use in all four countries has decreased over the study time period for commonly prescribed antibiotics in dentistry, i.e., the beta-lactams (Phenoxymethyl penicillin/Amoxicillin) and metronidazole. There were less numbers of prescriptions by dentists in Norway and Sweden compared to England and Scotland. Marked differences in some classes of antibiotics were noted with Phenoxymethyl penicillin dominating in Sweden/Norway compared to Amoxicillin and Metronidazole in England/Scotland. In England and Scotland, dentists were the largest prescribers of metronidazole in primary care. Clindamycin prescriptions was higher in Norway and Sweden. CONCLUSION: Noticeable differences exist in prescribing patterns for the management of oral infections. High levels of metronidazole use in England and Scotland also require further analysis. All countries over the study period showed a decrease in total numbers of antibiotics prescribed.

Antistreptococcal interventions for guttate and chronic plaque psoriasis.

BACKGROUND: Psoriasis is a chronic skin disease that affects approximately two per cent of the general population. Plaque psoriasis is the most common form: it usually appears as raised, red patches of inflamed skin, covered with silvery white scales. The patches often occur in a symmetrical pattern. Guttate psoriasis is a particular form of psoriasis with widespread, small erythematosquamous lesions. Streptococcal infection is suspected to be a triggering factor for the onset of guttate psoriasis, and flare-up of chronic plaque psoriasis. The previous Cochrane Review on this topic was published in 2000; it required an update because antistreptococcal treatment continues to be used to treat psoriasis, especially for the acute form of guttate psoriasis. OBJECTIVES: To assess the effects of antistreptococcal interventions for guttate and chronic plaque psoriasis. SEARCH METHODS: We searched Cochrane Skin Specialised Register, Cochrane Register of Studies Online, CENTRAL, MEDLINE, Embase, LILACS, and five trials registers (January 2019). We checked the reference lists of included and excluded studies and searched conference proceedings from the American Academy of Dermatology, Society for Investigative Dermatology, and European Academy of Dermatology and Venereology. SELECTION CRITERIA: We considered randomised controlled trials (RCTs) assessing antistreptococcal interventions (tonsillectomy or systemic antibiotic treatment) in people with clinically diagnosed acute guttate and chronic plaque psoriasis compared with placebo, no intervention, or each other. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. Primary outcome measures were: 1) time-to-resolution; achieving clear or almost clear skin (Physician Global Assessment (PGA) 0 or 1 or Psoriasis Area and Severity Index (PASI) 90 or 100); 2) proportion of participants with adverse effects and severe adverse effects. Secondary outcomes were: 1) proportion of participants achieving clear or almost clear skin; 2) proportion of participants achieving PASI 75 or PGA 1 to 2; 3) risk of having at least one relapse at long-term follow-up. Short-term assessment was defined as within eight weeks of the start of treatment; long-term was at least one year after the start of treatment. MAIN RESULTS: We included five trials (162 randomised participants); three were conducted in a hospital dermatology department. One study declared funding by a pharmaceutical company. Participants' ages ranged from 12 to 77 years; only two participants were younger than 15 years. Mean PASI score at baseline varied from 5.7 (i.e. mild) to 23 (i.e. severe) in four studies. Twenty-three of 162 participants had streptococcus-positive throat swab culture. We did not perform a meta-analysis due to heterogeneity of participants' characteristics and interventions.None of the trials measured our efficacy primary outcome, time-to-resolution, or the secondary outcome, risk of having at least one relapse at long-term follow-up.We rated the quality of the results as very low-quality evidence, due to high risk of bias (absence of blinding of participants and caregivers, and high risk of outcome reporting bias) and imprecision (single study data with a low number of events). Hence, we are very uncertain about the results presented.Guttate psoriasisOne three-armed trial (N = 43) assessed penicillin (50,000 international units (IU)/kg/day in three doses) versus erythromycin (250 mg four times per day) versus no treatment (treatment for 14 days, with six-week follow-up from start of treatment). Adverse events and the proportion of participants achieving clear or almost clear skin were not measured.One trial (N = 20) assessed penicillin (1.6 MU (million units) intramuscularly once a day) versus no treatment (six weeks of treatment, with eight-week follow-up from start of treatment). At six-week (short-term) follow-up, no adverse events were observed in either group, and there was no statistically significant difference between the two groups in the proportion of participants with clear or almost clear skin (risk ratio (RR) 2.00, 95% confidence interval (CI) 0.68 to 5.85).One trial (N = 20) assessed rifampicin (300 mg twice daily) versus placebo (14-day treatment duration; six-week follow-up from start of treatment); none of the review outcomes were measured.These trials did not measure the proportion of participants achieving PASI 75 or PGA 1 to 2.Chronic plaque psoriasisOne trial (N = 50) assessed long-term azithromycin treatment (500 mg daily dose) versus vitamin C. Adverse events were reported in the azithromycin group (10 out of 30 had nausea and mild abdominal upset), but not in the vitamin C group. The proportion of participants who achieved clear or almost clear skin was not measured. In the azithromycin group, 18/30 versus 0/20 participants in the vitamin C group reached PASI 75 at the end of 48 weeks of treatment (RR 25.06, 95% CI 1.60 to 393.59).One trial (N = 29) assessed tonsillectomy versus no treatment, with 24-month follow-up after surgery. One participant in the tonsillectomy group had minor bleeding. At eight-week follow-up, 1/15 in the tonsillectomy group, and 0/14 in the no treatment group achieved PASI 90; and 3/15 participants in the tonsillectomy group, and 0/14 in the no treatment group achieved PASI 75 (RR 6.56, 95% CI 0.37 to 116.7). AUTHORS' CONCLUSIONS: We found only five trials (N = 162), which assessed the effects of five comparisons (systemic antibiotic treatment (penicillin, azithromycin) or tonsillectomy). Two comparisons (erythromycin compared to no treatment, and rifampicin compared to placebo) did not measure any of the outcomes of interest. There was very low-quality evidence for the outcomes that were measured, Therefore, we are uncertain of both the efficacy and safety of antistreptococcal interventions for guttate and chronic plaque psoriasis.The included trials were at unclear or high risk of bias and involved only a small number of unrepresentative participants, with limited measurement of our outcomes of interest. The studies did not allow investigation into the influence of Streptococcal infection, and a key intervention (amoxicillin) was not assessed.Further trials assessing the efficacy and tolerance of penicillin V or amoxicillin are needed in children and young adults with guttate psoriasis.

Antibiotic prescription and clinical management of common infections among general practitioners in Latvia, Lithuania, and Sweden: a pilot survey with a simple protocol.

Comparative information on diagnosis-related antibiotic prescribing patterns are scarce from primary care within and between countries. To describe and compare antibiotic prescription and routine management of infections in primary care in Latvia (LV), Lithuania (LT) and two study sites in Sweden (SE), a cross-sectional observational study on patients who consulted due to sypmtoms compatible with infection was undetraken. Infection and treatment was detected and recorded by physicians only. Data was collected from altogether 8786 consecutive patients with infections in the three countries. Although the overall proportion of patients receiving an antibiotic prescription was similar in all three countries (LV and LT 42%, SE 38%), there were differences in the rate of prescription between the countries depending on the respective diagnoses. While penicillins dominated among prescriptions (LV 58%, LT 67%, SE 70%), phenoxymethylpenicillin was most commonly prescribed in Sweden (57% of all penicillins), while it was amoxicillin with or without clavulanic acid in Latvia (99%) and Lithuania (85%) respectively. Pivmecillinam and flucloxacillin, which accounted for 29% of penicillins in Sweden, were available neither in Latvia nor in Lithuania. The applied methodology was simple, and provided useful information on differences in treatment of common infections in ambulatory care in the absence of available computerized diagnosis-prescription data. Despite some limitations, the method can be used for assessment of intention to treat and compliance to treatment guidelines and benchmarking locally, nationally, or internationally, just as the point prevalence surveys (PPS) protocols have been used in hospitals all over Europe.

Systemic antibiotics for symptomatic apical periodontitis and acute apical abscess in adults.

BACKGROUND: Dental pain can have a detrimental effect on quality of life. Symptomatic apical periodontitis and acute apical abscess are common causes of dental pain and arise from an inflamed or necrotic dental pulp, or infection of the pulpless root canal system. Clinical guidelines recommend that the first-line treatment for teeth with these conditions should be removal of the source of inflammation or infection by local, operative measures, and that systemic antibiotics are currently only recommended for situations where there is evidence of spreading infection (cellulitis, lymph node involvement, diffuse swelling) or systemic involvement (fever, malaise). Despite this, there is evidence that dentists frequently prescribe antibiotics in the absence of these signs. There is concern that this could contribute to the development of antibiotic-resistant bacterial colonies within both the individual and the community. This review is an update of the original version that was published in 2014. OBJECTIVES: To evaluate the effects of systemic antibiotics provided with or without surgical intervention (such as extraction, incision and drainage of a swelling, or endodontic treatment), with or without analgesics, for symptomatic apical periodontitis and acute apical abscess in adults. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched the following databases: Cochrane Oral Health's Trials Register (to 26 February 2018), the Cochrane Central Register of Controlled Trials (CENTRAL; 2018, Issue 1) in the Cochrane Library (searched 26 February 2018), MEDLINE Ovid (1946 to 26 February 2018), Embase Ovid (1980 to 26 February 2018), and CINAHL EBSCO (1937 to 26 February 2018). The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. A grey literature search was conducted using OpenGrey (to 26 February 2018) and ZETOC Conference Proceedings (1993 to 26 February 2018). No restrictions were placed on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: Randomised controlled trials of systemic antibiotics in adults with a clinical diagnosis of symptomatic apical periodontitis or acute apical abscess, with or without surgical intervention (considered in this situation to be extraction, incision and drainage or endodontic treatment) and with or without analgesics. DATA COLLECTION AND ANALYSIS: Two authors screened the results of the searches against inclusion criteria, extracted data and assessed risk of bias independently and in duplicate. We calculated mean differences (MD) (standardised mean difference (SMD) when different scales were reported) and 95% confidence intervals (CI) for continuous data. A fixed-effect model was used in the meta-analysis as there were fewer than four studies. We contacted study authors to obtain missing information. MAIN RESULTS: We included two trials in this review, with 62 participants included in the analyses. Both trials were conducted in university dental schools in the USA and compared the effects of oral penicillin V potassium (penicillin VK) versus a matched placebo when provided in conjunction with a surgical intervention (total or partial pulpectomy) and analgesics to adults with acute apical abscess or symptomatic necrotic tooth. The patients included in these trials had no signs of spreading infection or systemic involvement (fever, malaise). We assessed one study as having a high risk of bias and the other study as having unclear risk of bias.The primary outcome variables reported in both studies were participant-reported pain and swelling (one trial also reported participant-reported percussion pain). One study reported the type and number of analgesics taken by participants. One study recorded the incidence of postoperative endodontic flare-ups (people who returned with symptoms that necessitated further treatment). Adverse effects, as reported in one study, were diarrhoea (one participant, placebo group) and fatigue and reduced energy postoperatively (one participant, antibiotic group). Neither study reported quality of life measurements.Objective 1: systemic antibiotics versus placebo with surgical intervention and analgesics for symptomatic apical periodontitis or acute apical abscessTwo studies provided data for the comparison between systemic antibiotics (penicillin VK) and a matched placebo for adults with acute apical abscess or a symptomatic necrotic tooth when provided in conjunction with a surgical intervention. Participants in one study all underwent a total pulpectomy of the affected tooth, while participants in the other study had their tooth treated by either partial or total pulpectomy. Participants in both trials received oral analgesics. There were no statistically significant differences in participant-reported measures of pain or swelling at any of the time points assessed within the review. The MD for pain (short ordinal numerical scale 0 to 3) was -0.03 (95% CI -0.53 to 0.47) at 24 hours; 0.32 (95% CI -0.22 to 0.86) at 48 hours; and 0.08 (95% CI -0.38 to 0.54) at 72 hours. The SMD for swelling was 0.27 (95% CI -0.23 to 0.78) at 24 hours; 0.04 (95% CI -0.47 to 0.55) at 48 hours; and 0.02 (95% CI -0.49 to 0.52) at 72 hours. The body of evidence was assessed as at very low quality.Objective 2: systemic antibiotics without surgical intervention for adults with symptomatic apical periodontitis or acute apical abscessWe found no studies that compared the effects of systemic antibiotics with a matched placebo delivered without a surgical intervention for symptomatic apical periodontitis or acute apical abscess in adults. AUTHORS' CONCLUSIONS: There is very low-quality evidence that is insufficient to determine the effects of systemic antibiotics on adults with symptomatic apical periodontitis or acute apical abscess.

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.

Survey of Spanish general practitioners' attitudes toward management of sore throat: an internet-based questionnaire study.

BACKGROUND: The management of sore throat varies widely in Europe. The objective of this study was to gain insight into clinicians' perceptions on the current management of sore throat in Spain. METHODS: Cross-sectional, internet-based questionnaire study answered from July to September 2013. General practitioners (GPs) affiliated with the two largest scientific societies of primary care were invited to participate in the study. Questions were asked about physician knowledge, the use of current national guidelines for sore throat management, and management in two clinical scenarios, depicting a young adult with sore throat and: 1. cough, coriza with or without fever, and 2. fever without cough and coriza. RESULTS: The questionnaire was completed by 1476 GPs (5%) and 12.7% declared using rapid antigen detection tests. Antibiotics were considered by 18.8% of the GPs in the first scenario and by 32% in the second scenario (p < 0.001). The antibiotics most commonly mentioned by GPs were amoxicillin and amoxicillin + clavulanate (52.7 and 31.2%, respectively) whereas penicillin V was only prescribed in 11.9% of the cases. The drugs most commonly considered in both scenarios were analgesics and anti-inflammatory drugs. Antitussives, decongestants and expectorants were more commonly prescribed in cases of suspected viral infection (p < 0.001). CONCLUSIONS: GPs have misconceptions as to the indications for using rapid antigen detection tests and prescribing drugs in the management of sore throat. These results suggest that guidelines are seldom followed since one in five GPs declared giving antibiotics for patients with a suspected viral infection and the use of second-choice antibiotics seems considerable.

Use of azithromycin and death from cardiovascular causes.

BACKGROUND: Azithromycin use is associated with an increased risk of death from cardiovascular causes among patients at high baseline risk. Whether azithromycin confers a similar risk in the unselected general population is unknown. METHODS: We conducted a nationwide historical cohort study involving Danish adults (18 to 64 years of age), linking registry data on filled prescriptions, causes of death, and patient characteristics for the period from 1997 through 2010. We estimated rate ratios for death from cardiovascular causes, comparing 1,102,050 episodes of azithromycin use with no use of antibiotic agents (matched in a 1:1 ratio according to propensity score, for a total of 2,204,100 episodes) and comparing 1,102,419 episodes of azithromycin use with 7,364,292 episodes of penicillin V use (an antibiotic with similar indications; analysis was conducted with adjustment for propensity score). RESULTS: The risk of death from cardiovascular causes was significantly increased with current use of azithromycin (defined as a 5-day treatment episode), as compared with no use of antibiotics (rate ratio, 2.85; 95% confidence interval [CI], 1.13 to 7.24). The analysis relative to an antibiotic comparator included 17 deaths from cardiovascular causes during current azithromycin use (crude rate, 1.1 per 1000 person-years) and 146 during current penicillin V use (crude rate, 1.5 per 1000 person-years). With adjustment for propensity scores, current azithromycin use was not associated with an increased risk of cardiovascular death, as compared with penicillin V (rate ratio, 0.93; 95% CI, 0.56 to 1.55). The adjusted absolute risk difference for current use of azithromycin, as compared with penicillin V, was -1 cardiovascular death (95% CI, -9 to 11) per 1 million treatment episodes. CONCLUSIONS: Azithromycin use was not associated with an increased risk of death from cardiovascular causes in a general population of young and middle-aged adults. (Funded by the Danish Medical Research Council.).

A randomized controlled study of 5 and 10 days treatment with phenoxymethylpenicillin for pharyngotonsillitis caused by streptococcus group A - a protocol study.

BACKGROUND: In 2014 the Swedish government assigned to The Public Health Agency of Sweden to conduct studies to evaluate optimal use of existing antibiotic agents. The aim is to optimize drug use and dosing regimens to improve the clinical efficacy. The present study was selected following a structured prioritizing process by independent experts. METHODS: This phase IV study is a randomized, open-label, multicenter study with non-inferiority design regarding the therapeutic use of penicillin V with two parallel groups. The overall aim is to study if the total exposure with penicillin V can be reduced from 1000 mg three times daily for 10 days to 800 mg four times daily for 5 days when treating Streptococcus pyogenes (Lancefield group A) pharyngotonsillitis. Patients will be recruited from 17 primary health care centers in Sweden. Adult men and women, youth and children ≥6 years of age who consult for sore throat and is judged to have a pharyngotonsillitis, with 3-4 Centor criteria and a positive rapid test for group A streptococci, will be included in the study. The primary outcome is clinical cure 5-7 days after discontinuation of antibiotic treatment. Follow-up controls will be done by telephone after 1 and 3 months. Throat symptoms, potential relapses and complications will be monitored, as well as adverse events. Patients (n = 432) will be included during 2 years. DISCUSSION: In the era of increasing antimicrobial resistance and the shortage of new antimicrobial agents it is necessary to revisit optimal usage of old antibiotics. Old antimicrobial drugs are often associated with inadequate knowledge on pharmacokinetics and pharmacodynamics and lack of optimized dosing regimens based on randomized controlled clinical trials. If a shorter and more potent treatment regimen is shown to be equivalent with the normal 10 day regimen this can imply great advantages for both patients (adherence, adverse events, resistance) and the community (resistance, drug costs). TRIAL REGISTRATION: EudraCT number 2015-001752-30 . Protocol FoHM/Tonsillit2015 date 22 June 2015, version 2. Approved by MPA of Sweden 3 July 2015, Approved by Regional Ethical Review Board in Lund, 25 June 2015.

Peer academic detailing on use of antibiotics in acute respiratory tract infections. A controlled study in an urban Norwegian out-of-hours service.

OBJECTIVE: To analyse if peer academic detailing by experienced general practitioners (GPs) could be a useful way to change Medical Doctors, (MDs) prescription of antibiotics for acute respiratory tract infections (ARTIs) in out-of-hours service. METHOD: An educational Intervention study based on prescription data among MDs working in an out-of-hours service from June 2006 through October 2008. Specially trained GPs lectured a peer educational program (3 × 45 minutes) about use of antibiotics for ARTIs according to national recommendations. OUTCOME MEASURES: The type and frequency of antibiotics prescribed for different ARTIs before and after intervention comparing the intervention group with the control group. SUBJECTS: 22 MDs in the intervention group and 31 MDs in the control group. RESULTS: The intervention group showed an overall statistically significantly absolute increase in the use of penicillin V (Penicillin V) of 9.8% (95% CI: 2.3%-17.4% p < 0.05), and similarly an statistically significantly absolute decrease in the use of macrolides and lincosamides of 8.8% (95% CI: 2.6%-14.9.2% p < 0.05) for all diagnoses. For subgroups of ARTIs we found a significant increase in the use of Penicillin V for acute otitis media, sinusitis, pneumonia and upper ARTIs. There was no significant changes in total prescription rates in the two groups. 41% of all consultations with respiratory tract infections resulted in antibiotic prescription. CONCLUSIONS: Using trained GPs to give peer academic detailing to colleagues in combination with open discussion on prescription, showed a significant change in prescription of antibiotics towards national guidelines. Key points Phenoxymethylpenicillin is the first choice for the most of respiratory tract infections when indicated. Despite the guidelines for the choice of antibiotics in Norway, general practitioners' choice often differs from these. We showed that a session of three times 45 min of peer academic detailing changed significantly the choice of antibiotics towards the National Guidelines in an urban Norwegian out-of-hours service.

Clinical practice guideline: tonsillitis I. Diagnostics and nonsurgical management.

More than 120,000 patients are treated annually in Germany to resolve repeated episodes of acute tonsillitis. Therapy is aiming at symptom regression, avoidance of complications, reduction in the number of disease-related absences in school or at work, increased cost-effectiveness and improved quality of life. The purpose of this part of the guideline is to provide clinicians in any setting with a clinically focused multi-disciplinary guidance through different conservative treatment options in order to reduce inappropriate variation in clinical care, improve clinical outcome and reduce harm. Surgical management in terms of intracapsular as well as extracapsular tonsillectomy (i.e. tonsillotomy) is the subject of part II of this guideline. To estimate the probability of tonsillitis caused by ß-hemolytic streptococci, a diagnostic scoring system according to Centor or McIsaac is suggested. If therapy is considered, a positive score of ≥3 should lead to pharyngeal swab or rapid test or culture in order to identify ß-hemolytic streptococci. Routinely performed blood tests for acute tonsillitis are not indicated. After acute streptococcal tonsillitis, there is no need to repeat a pharyngeal swab or any other routine blood tests, urine examinations or cardiological diagnostics such as ECG. The determination of the antistreptolysin O-titer (ASLO titer) and other antistreptococcal antibody titers do not have any value in relation to acute tonsillitis with or without pharyngitis and should not be performed. First-line therapy of ß-hemolytic streptococci consists of oral penicillin. Instead of phenoxymethylpenicillin-potassium (penicillin V potassium), also phenoxymethlpenicillin-benzathine with a clearly longer half-life can be used. Oral intake for 7 days of one of both the drugs is recommended. Alternative treatment with oral cephalosporins (e.g. cefadroxil, cefalexin) is indicated only in cases of penicillin failure, frequent recurrences, and whenever a more reliable eradication of ß-hemolytic streptococci is desirable. In cases of allergy or incompatibility of penicillin, cephalosporins or macrolides (e.g. Erythromycin-estolate) are valuable alternatives.

Obesity and risk of infection: results from the Danish Blood Donor Study.

BACKGROUND: It is well known that obesity complicates the course of several diseases. However, it is unknown whether obesity affects the risk of infection among healthy individuals. METHODS: We included 37,808 healthy participants from the Danish Blood Donor Study, who completed a questionnaire on health-related items. Obesity was defined as a body mass index ≥ 30 kg/m(2). Infections among participants were identified by relevant ICD-10 codes in the Danish National Patient Register and Anatomical Therapeutic Chemical (ATC) codes in the Danish Prescription Register. Multivariable Cox proportional hazards analysis with age as the underlying timescale was used as the statistical model. RESULTS: During 113,717 person-years of observation, 1,233 participants were treated for infection at a hospital. Similarly, during 58,411 person-years of observation, 15,856 participants filled at least one prescription of antimicrobials. Obesity was associated with risk of hospital-based treatment for infection (women: hazard ratio [HR] = 1.5, 95% confidence interval [CI] = 1.1, 1.9; men: HR = 1.5, 95% CI = 1.2, 1.9). For specific infections, obesity was associated with increased risk of abscesses (both sexes), infections of the skin and subcutaneous tissue (men), and respiratory tract infections and cystitis (women). Similarly, obesity was associated with filled prescriptions of antimicrobials overall (women: HR = 1.22, 95% CI = 1.14, 1.30; men: HR = 1.23, 95% CI: 1.15, 1.33) and particularly with phenoxymethylpenicillin, macrolides, dicloxacillin and flucloxacillin, and broad-spectrum penicillins. CONCLUSIONS: In a large cohort of healthy individuals, obesity was associated with risk of infection. This result warrants further studies of metabolism and the immune response.

Antibiotics for acute laryngitis in adults.

BACKGROUND: This is an update of the original review published in 2005. Acute laryngitis is a common illness worldwide. Diagnosis is often made by case history alone and treatment often targets symptoms. OBJECTIVES: To assess the effectiveness and safety of different antibiotic therapies in adults with acute laryngitis. A secondary objective was to report the rates of adverse events associated with these treatments. SEARCH METHODS: We searched CENTRAL (2014, Issue 11), MEDLINE (January 1966 to November week 3, 2014), EMBASE (1974 to December 2014), LILACS (1982 to December 2014) and BIOSIS (1980 to December 2014). SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing any antibiotic therapy with placebo for acute laryngitis. The main outcome was objective voice scores. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted and synthesised data. MAIN RESULTS: We included three RCTs (351 participants) that had moderate to high risk of bias. The quality of the evidence was very low for all outcomes. We downgraded the studies because of limitations in study design or execution (risk of bias), imprecision and inconsistency of results. We included a new trial presented only as a conference abstract in this update.In one study of acute laryngitis in adults, 100 participants were randomised to receive penicillin V (800 mg twice daily for five days) or an identical placebo. A recording of each patient reading a standardised text was made at the first visit, during re-examination after one and two weeks, and at follow-up after two to six months. No significant differences were found between the groups. The trial also measured symptoms reported by participants and found no significant differences.One study investigated erythromycin for acute laryngitis in 106 adults. The mean objective voice scores measured at the first visit, at re-examination after one and two weeks, and at follow-up after two to six months did not significantly differ between the groups. At one week there were significant beneficial differences in the severity of reported vocal symptoms (slight, moderate and severe) as judged by participants (P value = 0.042). However, the rates of participants having improved voice disturbance (subjective symptoms) at one and two weeks were not significantly different among groups. Comparing erythromycin and placebo groups on the rate of persistence of cough at two weeks, the risk ratio (RR) was 0.38 (95% confidence interval (CI) 0.15 to 0.97, P value = 0.04) and the number needed to treat for an additional beneficial outcome (NNTB) was 5.87 (95% CI 3.09 to 65.55). We calculated a RR of 0.64 (95% CI 0.46 to 0.90, P value = 0.034) and a NNTB of 3.76 (95% CI 2.27 to 13.52; P value = 0.01) for the subjective voice scores at one week.A third trial from Russia included 145 patients with acute laryngitis symptoms. Participants were randomised to three treatment groups: Group 1: seven-day course of fusafungine (six times a day by inhalation); Group 2: seven-day course of fusafungine (six times a day by inhalation) plus clarithromycin (250 mg twice daily for seven days); Group 3: no treatment. Clinical cure rates were measured at days 5 ± 1, 8 ± 1 and 28 ± 2. The authors reported significant differences in the rates of clinical cure at day 5 ± 1 favouring fusafungine (one trial; 93 participants; RR 1.50, 95% CI 1.02 to 2.20; P value = 0.04) and fusafungine plus clarithromycin (one trial 97 participants; RR 1.47, 95% CI 1.00 to 2.16; P value = 0.05) when compared to no treatment. However, no significant differences were found at days 8 ± 1 and 28 ± 2. Also, no significant differences were found when comparing fusafungine to fusafungine plus clarithromycin at days 5 ± 1, 8 ± 1 and 28 ± 2. AUTHORS' CONCLUSIONS: Antibiotics do not appear to be effective in treating acute laryngitis when assessing objective outcomes. They appear to be beneficial for some subjective outcomes. Erythromycin could reduce voice disturbance at one week and cough at two weeks when measured subjectively. Fusafungine could increase the cure rate at day five. The included RCTs had important methodological problems and these modest benefits from antibiotics may not outweigh their cost, adverse effects or negative consequences for antibiotic resistance patterns.

Systemic antibiotics for symptomatic apical periodontitis and acute apical abscess in adults.

BACKGROUND: Dental pain can have a considerable detrimental effect on an individual's quality of life. Symptomatic apical periodontitis and acute apical abscess are common causes of dental pain and arise from an inflamed or necrotic dental pulp, or infection of the pulpless root canal system. Clinical guidelines recommend that the first-line treatment for teeth with symptomatic apical periodontitis or an acute apical abscess should be removal of the source of inflammation or infection by local, operative measures, and that systemic antibiotics are currently only recommended for situations where there is evidence of spreading infection (cellulitis, lymph node involvement, diffuse swelling) or systemic involvement (fever, malaise). Despite this, there is evidence that dentists continue to prescribe antibiotics for these conditions. There is concern that this could contribute to the development of antibiotic-resistant bacterial colonies both within the individual and within the community as a whole. OBJECTIVES: To evaluate the effects of systemic antibiotics provided with or without surgical intervention (such as extraction, incision and drainage of a swelling or endodontic treatment), with or without analgesics, for symptomatic apical periodontitis or acute apical abscess in adults. SEARCH METHODS: We searched the following electronic databases: Cochrane Oral Health Group's Trials Register (to 1 October 2013); Cochrane Central Register of Controlled Trials (The Cochrane Library 2013, Issue 9); MEDLINE via OVID (1946 to 1 October 2013); EMBASE via OVID (1980 to 1 October 2013) and CINAHL via EBSCO (1980 to 1 October 2013). We searched the World Health Organization (WHO) International Trials Registry Platform and the US National Institutes of Health Trials Registry (ClinicalTrials.gov) on 1 October 2013 to identify ongoing trials. We searched for grey literature using OpenGrey (to 1 October 2013) and ZETOC Conference Proceedings (1993 to 1 October 2013). We placed no restrictions on the language or date of publication when searching the electronic databases. SELECTION CRITERIA: Randomised controlled trials of systemic antibiotics in adults with a clinical diagnosis of symptomatic apical periodontitis or acute apical abscess, with or without surgical intervention (considered in this situation to be extraction, incision and drainage or endodontic treatment) and with or without analgesics. DATA COLLECTION AND ANALYSIS: Two review authors screened the results of the searches against inclusion criteria, extracted data and assessed risk of bias independently and in duplicate. We calculated mean differences (MD) (standardised mean difference (SMD) when different scales were reported) and 95% confidence intervals (CI) for continuous data and, where results were meta-analysed, we used a fixed-effect model as there were fewer than four studies. We contacted study authors to obtain missing information. MAIN RESULTS: We included two trials in this review, with 62 participants included in the analyses. Both trials were conducted in university dental schools in the USA and compared the effects of oral penicillin V potassium (penicillin VK) versus a matched placebo given in conjunction with a surgical intervention (total or partial pulpectomy) and analgesics to adults with acute apical abscess or symptomatic necrotic tooth (no signs of spreading infection or systemic involvement (fever, malaise)). We assessed one study as having a high risk of bias and the other study as having unclear risk of bias.The primary outcome variables presented were participant-reported pain and swelling (one trial also reported participant-reported percussion pain). One study reported the type and number of analgesics taken by participants. One study recorded the incidence of postoperative endodontic flare-ups (people who returned with symptoms that necessitated further treatment). Adverse effects as reported in one study were diarrhoea (one participant, placebo group) and fatigue and reduced energy postoperatively (one participant, antibiotic group). No studies reporting quality of life measurements were suitable for inclusion. Objective 1: systemic antibiotics versus placebo with surgical intervention and analgesics for symptomatic apical periodontitis or acute apical abscess. Two studies provided data for the comparison between systemic antibiotics (penicillin VK) and a matched placebo for adults with acute apical abscess or a symptomatic necrotic tooth. Participants in one study all underwent a total pulpectomy of the affected tooth while participants in the other study had their tooth treated by either partial or total pulpectomy. Participants in both trials received oral analgesics. There were no statistically significant differences in participant-reported measures of pain or swelling at any of the time points assessed within the review. The MD for pain (short ordinal numerical scale 0 to 3) was -0.03 (95% CI -0.53 to 0.47) at 24 hours; 0.32 (95% CI -0.22 to 0.86) at 48 hours and 0.08 (95% CI -0.38 to 0.54) at 72 hours. The SMD for swelling was 0.27 (95% CI -0.23 to 0.78) at 24 hours; 0.04 (95% CI -0.47 to 0.55) at 48 hours and 0.02 (95% CI -0.49 to 0.52) at 72 hours. The body of evidence was assessed as at very low quality. Objective 2: systemic antibiotics without surgical intervention for adults with symptomatic apical periodontitis or acute apical abscess. We found no studies that compared the effects of systemic antibiotics with a matched placebo delivered without a surgical intervention for symptomatic apical periodontitis or acute apical abscess in adults. AUTHORS' CONCLUSIONS: There is very low quality evidence that is insufficient to determine the effects of systemic antibiotics on adults with symptomatic apical periodontitis or acute apical abscess.

Imported toxigenic cutaneous diphtheria in a young male returning from Mozambique to Norway, March 2014.

Six outbreaks of infectious syphilis in the United Kingdom, ongoing since 2012, have been investigated among men who have sex with men (MSM) and heterosexual men and women aged under 25 years. Interventions included case finding and raising awareness among healthcare professionals and the public. Targeting at-risk populations was complicated as many sexual encounters involved anonymous partners. Outbreaks among MSM were influenced by the use of geospatial real-time networking applications that allow users to locate other MSM within close proximity.

Antibiotic prophylaxis patterns of Finnish dentists performing dental implant surgery.

BACKGROUND: The peri-operative use of prophylactic antibiotics in clinically healthy patients undergoing dental implant surgery is very common in Finland. While antibiotics are prescribed with the hope of preventing both local and systemic complications, their application and utilization is not uniform. OBJECTIVE: The aim of this study was to assess the variation in prescribing patterns among Finnish dentists performing dental implant placement operations. This study also aimed to examine the possible relationship between early implant removal and the use of the prophylactic antibiotics in Finland. MATERIALS AND METHODS: The National Institute for Health and Welfare in Finland granted permission to access the Finnish Dental Implant Register. The peri-operative antibiotic prophylaxis prescribing patterns were assessed in a total of 110 543 dental implant placement procedures and 1038 dental implant removal operations performed in Finland between April 1994 and April 2012. RESULTS: A total of 61 different antibiotics or combinations were prescribed peri-operatively during implant placements in Finland between 1994-2012. Phenoxymethylpenicillin was the most commonly prescribed drug (72.2%). No statistically significant difference in early implant removal rates could be found between patients who had or had not received peri-operative prophylaxis. However, patients who had received peri-operative prophylaxis had statistically significant longer implant survival rates. CONCLUSION: There is a variation in antibiotic prescribing patterns among Finnish dentists placing dental implants. The results suggest that the use of prophylactic antibiotics has little effect on the prevention of primary implant surgery-related complications and, hence, success rates.

A systematic review of effectiveness of daily oral penicillin v prophylaxis in the prevention of pneumococcal infection in children with sickle cell anaemia.

BACKGROUND: Children with sickle cell anaemia (SCA) are highly susceptible to infection caused by pneumococcal bacteria due to functional asplenia amongst other reasons. Pneumococcal infections are severe with high mortality among these children that the need for prophylactic penicillin therapy becomes necessary. The objective of this review is to look for evidence of the effectiveness of daily oral penicillin prophylaxis in the prevention of pneumococcal infection in children with SCA. METHODS: Electronic databases including genetic disorders group haemoglobinopathies trial register, Cochrane library, Pubmed, Turning Research Into Practice (TRIP) and Google were searched for relevant studies. Hand and grey literature searches were also done. Randomized controlled trials comparing oral penicillin prophylaxis for the prevention of pneumococcal infection in children with SCA with placebo or no treatment were searched for. RESULTS: Two trials were found to have met the inclusion criteria for the review. Results of the two included randomized controlled trials showed a significant reduction in the incidence of pneumococcal infection among children with SCA (and (0)-thallasaemia) receiving penicillin compared to the control group treated with placebo. The odds ratios for the two (Gaston et al and Falletta et al) studies were 0.37 (95% CI 0.16 to 0.86) and 0.5 (95% CI 0.1 to 2.71) respectively. CONCLUSION: There is strong evidence that daily oral penicillin prophylaxis greatly reduces the risk of pneumococcal infection in children with SCA under the age of three years and a moderately strong evidence that its, withdrawal at the age of five years did not result in any serious consequences.

Insufficient evidence of the effect of systemic antibiotics on adults with symptomatic apical periodontitis or acute apical abscess.

DATA SOURCES: The Cochrane Oral Health Groups Trials Register, Cochrane Central Register of Controlled Trials, Medline, Embase, CINAHL, OpenGrey, ZETOC Conference Proceedings World Health Organization (WHO) International Trials Registry Platform and the US National Institutes of Health Trials Registry databases were searched with no restrictions on the language or date of publication. STUDY SELECTION: Randomised controlled trials of systemic antibiotics in adults with a clinical diagnosis of symptomatic apical periodontitis or acute apical abscess, with or without surgical intervention (considered in this situation to be extraction, incision and drainage or endodontic treatment) and with or without analgesics. DATA EXTRACTION AND SYNTHESIS: Study selection, data abstraction and risk of bias assessment were carried out independently by two reviewers. RESULTS: Two trials involving 62 patients were included. They compared the effects of oral penicillin V potassium versus a matched placebo given in conjunction with a surgical intervention and analgesics to adults with an acute apical abscess or symptomatic necrotic tooth. One study was considered to have a high risk of bias and the other an unclear risk of bias. The primary outcomes were patient-reported pain and swelling. There were no statistically significant differences in participant-reported measures of pain or swelling at any of the time points assessed within the review. The body of evidence was assessed as at very low quality. CONCLUSIONS: There is very low quality evidence that is insufficient to determine the effects of systemic antibiotics on adults with symptomatic apical periodontitis or acute apical abscess.