The efficacy of pivmecillinam in oral step-down treatment in hospitalised patients with E. coli bacteremic urinary tract infection; a single-arm, uncontrolled treatment study.

BACKGROUND: The role of oral beta-lactam antibiotics in treating febrile urinary tract infections (UTI) is not yet definite. Today, fluoroquinolones together with trimethoprim-sulfamethoxazole (TMP-MTX) are considered standard of care and often the only available evidence-based oral treatment for febrile UTI. This study clarifies the efficacy and safety of pivmecillinam (PIV) used as step-down therapy for bacteremic urinary tract infection (UTI). METHODS: A single-arm, uncontrolled treatment trial was conducted in the period September 2017-March 2020. Candidates for inclusion were men and women suffering from E. coli bacteremia due to UTI and were consecutively included in a Norwegian hospital. Exclusion criteria were among others: other ongoing bacterial infection, septic shock, pyonephrosis/abscess and pregnancy. After 3 days of parenteral antibiotic, the treatment was converted to the study drug; oral PIV 400 mg QID for 1 week. Primary endpoint was a combination of three elements; afebrility, no need for retreatment and improvement in self-reported health status. Test Of Cure (TOC) was 1 week post-treatment. Secondary endpoints included among others microbiological efficacy and CRP value < 30 mg/L. RESULTS: Of 476 screened subjects, 53 patients were included. Median age was 67 years, 28 (56%) were women. 50 patients were evaluated for per-protocol analysis. 44 of 50 patients (88%) (95% CI [75.7-95.5]) reached the primary endpoint on TOC. 14 of 48 patients (29.2%) had significant growth (> 103 CFU/mL) of E.coli on TOC. CRP-level was strongly associated to treatment outcome, (OR 0.006 [95% CI 0.00-0.11], p < 0.001). CONCLUSIONS: This trial documents that PIV 400 mg QID given for 1 week following 3 days of parenteral antibiotics, is a suitable treatment option in patients suffering from bacteremic UTI due to E. coli. Randomised clinical trials studying the efficacy of PIV vs standard of care of febrile UTI are warranted. Trial registration The trial was registered at ClinicalTrials.gov under the identifier: NCT03282006 13/09/2017 and approved by The Regional Committees for Medical Research Ethics South East Norway (2015/2384/REK sør-øst) and the Norwegian Medicines Agency (SLV; reference No 16/06018-09; EudraCT No 2016-000984-18) before initiation.

Decisions on antibiotic prescribing for suspected urinary tract infections in frail older adults: a qualitative study in four European countries.

BACKGROUND: a suspected urinary tract infection (UTI) is the most common reason to prescribe antibiotics in a frail older patient. Frequently, antibiotics are prescribed unnecessarily. To increase appropriate antibiotic use for UTIs through antibiotic stewardship interventions, we need to thoroughly understand the factors that contribute to these prescribing decisions. OBJECTIVES: (1) to obtain insight into factors contributing to antibiotic prescribing for suspected UTIs in frail older adults. (2) To develop an overarching model integrating these factors to guide the development of antibiotic stewardship interventions for UTIs in frail older adults. METHODS: we conducted an exploratory qualitative study with 61 semi-structured interviews in older adult care settings in Poland, the Netherlands, Norway and Sweden. We interviewed physicians, nursing staff, patients and informal caregivers. RESULTS: participants described a chain of decisions by patients, caregivers and/or nursing staff preceding the ultimate decision to prescribe antibiotics by the physician. We identified five themes of influence: (1) the clinical situation and its complexity within the frail older patient, (2) diagnostic factors, such as asymptomatic bacteriuria, (3) knowledge (gaps) and attitude, (4) communication: interprofessional, and with patients and relatives and (5) context and organisation of care, including factors such as availability of antibiotics (over the counter), antibiotic stewardship efforts and factors concerning out-of-hours care. CONCLUSIONS: decision-making on suspected UTIs in frail older adults is a complex, multifactorial process. Due to the diverse international setting and stakeholder variety, we were able to provide a comprehensive overview of factors to guide the development of antibiotic stewardship interventions.

Clinical prediction of laboratory-confirmed influenza in adults with influenza-like illness in primary care. A randomized controlled trial secondary analysis in 15 European countries.

BACKGROUND: Clinical findings do not accurately predict laboratory diagnosis of influenza. Early identification of influenza is considered useful for proper management decisions in primary care. OBJECTIVE: We evaluated the diagnostic value of the presence and the severity of symptoms for the diagnosis of laboratory-confirmed influenza infection among adults presenting with influenza-like illness (ILI) in primary care. METHODS: Secondary analysis of patients with ILI who participated in a clinical trial from 2015 to 2018 in 15 European countries. Patients rated signs and symptoms as absent, minor, moderate, or major problem. A nasopharyngeal swab was taken for microbiological identification of influenza and other microorganisms. Models were generated considering (i) the presence of individual symptoms and (ii) the severity rating of symptoms. RESULTS: A total of 2,639 patients aged 18 or older were included in the analysis. The mean age was 41.8 ± 14.7 years, and 1,099 were men (42.1%). Influenza was microbiologically confirmed in 1,337 patients (51.1%). The area under the curve (AUC) of the model for the presence of any of seven symptoms for detecting influenza was 0.66 (95% confidence interval [CI]: 0.65-0.68), whereas the AUC of the symptom severity model, which included eight variables-cough, fever, muscle aches, sweating and/or chills, moderate to severe overall disease, age, abdominal pain, and sore throat-was 0.70 (95% CI: 0.69-0.72). CONCLUSION: Clinical prediction of microbiologically confirmed influenza in adults with ILI is slightly more accurate when based on patient reported symptom severity than when based on the presence or absence of symptoms.

Influenza is usually diagnosed clinically. However, the accuracy of a diagnosis of influenza based on clinical features is limited because symptoms overlap considerably with those caused by other microorganisms. This study examined whether identification of the severity rather than the presence of key signs and symptoms could aid in the diagnosis of influenza, thereby helping clinicians to determine when antiviral agent use is appropriate. The authors used the database of a previous randomized clinical trial on the effectiveness of an antiviral carried out in primary care centers in 15 countries in Europe during three epidemic periods from 2015/2016 to 2017/2018. Participants with influenza symptoms were included and they were asked about the presence and severity of different symptoms during the baseline visit with their doctors and a nasopharyngeal swab was taken for microbiological analysis. Overall, only 51% of the patients aged 18 or older had a confirmed influenza infection. Clinical findings are not particularly useful for confirming or excluding the diagnosis of influenza. However, the results of our study recommend considering how intense the different symptoms are, since key symptoms rated as moderate or severe are slightly better for predicting flu rather than the presence or absence of these symptoms.

Barriers and facilitators of appropriate antibiotic use in primary care institutions after an antibiotic quality improvement program - a nested qualitative study.

BACKGROUND: Antibiotic prescribing by physicians in primary care institutions is common and affected by several factors. Diagnosis and treatment of infections in a nursing home (NH) resident is challenging, with the risk of both under- and overtreatment. Identifying barriers and facilitators of appropriate antibiotic prescribing in NHs and municipal acute care units (MACUs) is essential to ensure the most adequate antibiotic treatment possible and develop future antibiotic stewardship programs. METHODS: After implementing a one-year antibiotic quality improvement program, we conducted six semi-structured focus group interviews with physicians (n = 11) and nurses (n = 14) in 10 NHs and 3 MACUs located in the county of Østfold, Norway. We used a semi-structured interview guide covering multiple areas influencing antibiotic use to identify persistent barriers and facilitators of appropriate antibiotic prescribing after the intervention. The interviews were audio-recorded and transcribed verbatim. The content analysis was performed following the six phases of thematic analysis developed by Braun and Clarke. RESULTS: We identified thirteen themes containing barriers and facilitators of the appropriateness of antibiotic use in primary care institutions. The themes were grouped into four main levels: Barriers and facilitators 1) at the clinical level, 2) at the resident level, 3) at the next of kin level, and 4) at the organisational level. Unclear clinical presentation of symptoms and lack of diagnostic possibilities were described as essential barriers to appropriate antibiotic use. At the same time, increased availability of the permanent nursing home physician and early and frequent dialogue with the residents' next of kin were emphasized as facilitators of appropriate antibiotic use. The influence of nurses in the decision-making process regarding infection diagnostics and treatment was by both professions described as profound. CONCLUSIONS: Our qualitative study identified four main levels containing several barriers and facilitators of appropriate antibiotic prescribing in Norwegian NHs and MACUs. Diagnostic uncertainty, frequent dialogue with next of kin and organisational factors should be targeted in future antibiotic stewardship programs in primary care institutions. In addition, for such programs to be as effective as possible, nurses should be included on equal terms with physicians.

Preventive effect of methenamine in women with recurrent urinary tract infections - a case-control study.

BACKGROUND: Urinary tract infection (UTI) is the most common bacterial infection in women. In Norwegian general practice, methenamine has been prescribed for many years as long-term prevention and accounted for 20% of the total antibiotic prescribing in 2015, as measured in defined daily dosages (DDDs). The efficacy of methenamine is unknown. If shown to be effective, this drug may become an important preventive against UTI. OBJECTIVE: To examine whether methenamine is preventive against recurrent UTI in women. DESIGN: Data for all antibiotics used for UTIs dispensed from all pharmacies from 2005 to 2015 were collected from the Norwegian prescription database (NorPD). SUBJECTS: Women aged ≥ 40 years with recurrent UTI, defined as ≥3 courses of UTI antibiotic/year, were included. MAIN OUTCOME MEASURES: Patients using methenamine (cases) and those not using methenamine (controls) were compared. The numbers of UTI prescriptions during the 2 years before and after inclusion were analysed. Results: The yearly prevalence for recurrent UTI was 2.4% in women ≥ 40 years. The change in antibiotic use from 2 years before to 2 years after inclusion in the study differed significantly between groups: 44.6 and 34.9% reductions in the number of antibiotic prescriptions for UTI in the methenamine and control groups, respectively. The decrease in UTI antibiotic prescriptions (58.9%) was greater in patients with a higher consumption of antibiotics before starting methenamine. CONCLUSIONS: Methenamine seems to be effective against recurrent UTI over the time span studied. The effect seems to be greater in patients with the highest number of recurrent UTIs. Key pointsMethenamine has been used for many years for prevention of recurrent UTI, but no studies have demonstrated a significant preventive effect of long time use.This study shows that methenamine seems to be effective for prevention in patients having recurrent UTI over 2 years or more.The effect seems to be larger in patients with a high number of UTIs over 2 years.

Experiences with a structured conversation tool: a qualitative study on feasibility in general practice in Norway.

OBJECTIVE: To study the feasibility of a structured conversation tool (ICIT) in Norwegian general practice. DESIGN AND PARTICIPANTS: A structured conversation tool with elements from Cognitive Behavioral Therapy (CBT) was developed for use at the encounter in general practice to increase patient's self-coping ability and the GPs management and sick leave assessment in patients with MUPS. Eight GPs received training and used the ICIT on 49 patients with MUPS. The physicians were gathered into two focus groups. The interviews were recorded on tape, transcribed, and analyzed with systematic text condensation. MAIN OUTCOME MEASURES: The aim of our study was to examine any benefit and the feasibility of the ICIT in general practice. RESULTS: The physicians found the ICIT helpful to sort out, clarify and concretize the patients' issues. They felt less fatigued as patients took on a greater responsibility for their own recovery and reported a greater satisfaction and better management with the patients. A salutogenic approach gave the physicians greater insight into their patients' lives and their issues, opening for new treatment options and aiding in recovery. By focusing on the patient's potential capabilities despite their medical condition, some physicians experienced that patients on sick leave returned to work quicker. CONCLUSIONS: The GPs in this study reported that the ICIT was helpful in consultations with patients due to unspecific medical conditions and facilitated a sense of competence for the physician. KEY POINTSGPs need communication skill training for integrated treatment and sick leave assessment for patients with Medically Unexplained Physical Symptoms (MUPS).•The GPs experienced that the structured conversation tool was beneficial in structuring, clarifying, and substantiating the patient's problems.•The GPs experienced a greater insight into their patients and their issues, opening new treatment options and aiding in recovery.•The GPs experienced patients' quicker recovery and returns to work by starting immediate treatment using the conversation tool.

Oseltamivir plus usual care versus usual care for influenza-like illness in primary care: an open-label, pragmatic, randomised controlled trial.

BACKGROUND: Antivirals are infrequently prescribed in European primary care for influenza-like illness, mostly because of perceived ineffectiveness in real world primary care and because individuals who will especially benefit have not been identified in independent trials. We aimed to determine whether adding antiviral treatment to usual primary care for patients with influenza-like illness reduces time to recovery overall and in key subgroups. METHODS: We did an open-label, pragmatic, adaptive, randomised controlled trial of adding oseltamivir to usual care in patients aged 1 year and older presenting with influenza-like illness in primary care. The primary endpoint was time to recovery, defined as return to usual activities, with fever, headache, and muscle ache minor or absent. The trial was designed and powered to assess oseltamivir benefit overall and in 36 prespecified subgroups defined by age, comorbidity, previous symptom duration, and symptom severity, using a Bayesian piece-wise exponential primary analysis model. The trial is registered with the ISRCTN Registry, number ISRCTN 27908921. FINDINGS: Between Jan 15, 2016, and April 12, 2018, we recruited 3266 participants in 15 European countries during three seasonal influenza seasons, allocated 1629 to usual care plus oseltamivir and 1637 to usual care, and ascertained the primary outcome in 1533 (94%) and 1526 (93%). 1590 (52%) of 3059 participants had PCR-confirmed influenza infection. Time to recovery was shorter in participants randomly assigned to oseltamivir (hazard ratio 1·29, 95% Bayesian credible interval [BCrI] 1·20-1·39) overall and in 30 of the 36 prespecified subgroups, with estimated hazard ratios ranging from 1·13 to 1·72. The estimated absolute mean benefit from oseltamivir was 1·02 days (95% [BCrI] 0·74-1·31) overall, and in the prespecified subgroups, ranged from 0·70 (95% BCrI 0·30-1·20) in patients younger than 12 years, with less severe symptoms, no comorbidities, and shorter previous illness duration to 3·20 (95% BCrI 1·00-5·50) in patients aged 65 years or older who had more severe illness, comorbidities, and longer previous illness duration. Regarding harms, an increased burden of vomiting or nausea was observed in the oseltamivir group. INTERPRETATION: Primary care patients with influenza-like illness treated with oseltamivir recovered one day sooner on average than those managed by usual care alone. Older, sicker patients with comorbidities and longer previous symptom duration recovered 2-3 days sooner. FUNDING: European Commission's Seventh Framework Programme.

Does C-reactive protein predict time to recovery and benefit from oseltamivir treatment in primary care patients with influenza-like illness? A randomized controlled trial secondary analysis.

OBJECTIVE: Recovery time and treatment effect of oseltamivir in influenza-like illness (ILI) differs between patient groups. A point-of-care test to better predict ILI duration and identify patients who are most likely to benefit from oseltamivir treatment would aid prescribing decisions in primary care. This study aimed to investigate whether a C-reactive protein (CRP) concentration of ≥30 mg/L can predict (1) ILI disease duration, and (2) which patients are most likely to benefit from oseltamivir treatment. DESIGN: Secondary analysis of randomized controlled trial data. SETTING: Primary care in Lithuania, Sweden and Norway during three consecutive influenza seasons 2016-2018. SUBJECTS: A total of 277 ILI patients aged one year or older and symptom duration of ≤72 h. MAIN OUTCOME MEASURES: Capillary blood CRP concentration at baseline, and ILI recovery time defined as having 'returned to usual daily activity' with residual symptoms minimally interfering. RESULTS: At baseline, 20% (55/277) had CRP concentrations ≥30mg/L (range 0-210). CRP concentration ≥30 mg/L was not associated with recovery time (adjusted hazards ratio (HR) 0.80: 95% CI 0.50-1.3; p = 0.33). Interaction analysis of CRP concentration ≥30 mg/L and oseltamivir treatment did not identify which patients benefit more from oseltamivir treatment (adjusted HR 0.69: 95% CI 0.37-1.3; p = 0.23). CONCLUSION: There was no association between CRP concentration of ≥30 mg/L and recovery time from ILI. Furthermore, CRP could not predict which ILI patients benefit more from oseltamivir treatment. Hence, we do not recommend CRP testing for predicting ILI recovery time or identifying patients who will receive particular benefit from oseltamivir treatment.Key PointsPredicting disease course of influenza-like illness (ILI), and identifying which patients benefit from oseltamivir treatment is a challenge for physicians.• There was no association between CRP concentration at baseline and recovery time in patients consulting with ILI in primary care.• There was no association between CRP concentration at baseline and benefit from oseltamivir treatment.• We, therefore, do not recommend CRP testing for predicting recovery time or in decision-making concerning oseltamivir prescribing in ILI patients.

Is C-reactive protein associated with influenza A or B in primary care patients with influenza-like illness? A cross-sectional study.

OBJECTIVE: Identifying influenza A or B as cause of influenza-like illness (ILI) is a challenge due to non-specific symptoms. An accurate, cheap and easy to use biomarker might enhance targeting influenza-specific management in primary care. The aim of this study was to investigate if C-reactive protein (CRP) is associated with influenza A or B, confirmed with PCR testing, in patients presenting with ILI. DESIGN: Cross-sectional study. SETTING: Primary care in Lithuania, Norway and Sweden. SUBJECTS: A total of 277 patients at least 1 year of age consulting primary care with ILI during seasonal influenza epidemics. MAIN OUTCOME MEASURES: Capillary blood CRP analysed as a point-of-care test and detection of influenza A or B on nasopharyngeal swabs in adults, and nasal and pharyngeal swabs in children using PCR. RESULTS: The prevalence of positive tests for influenza A among patients was 44% (121/277) and the prevalence of influenza B was 21% (58/277). Patients with influenza A infection could not be identified based on CRP concentration. However, increasing CRP concentration in steps of 10 mg/L was associated with a significantly lower risk for influenza B with an adjusted odds ratio of 0.42 (0.25-0.70; p<.001). Signs of more severe symptoms like shortness of breath, sweats or chills and dizziness were associated with higher CRP. CONCLUSIONS: There was no association between CRP and influenza A. Increased concentration of CRP was associated with a lower risk for having influenza B, a finding that lacks clinical usefulness. Hence, CRP testing should be avoided in ILI, unless bacterial pneumonia is suspected. Key points Identifying influenza A or B as cause of influenza-like illness (ILI) is a challenge due to non-specific symptoms. There was no association between concentration of CRP and influenza A. Increased concentration of CRP was associated with a lower risk for having influenza B, a finding that lacks clinical usefulness. A consequence is that CRP testing should be avoided in ILI, unless bacterial pneumonia or similar is suspected.

Predictors for outcome in acute lateral epicondylitis.

BACKGROUND: Lateral epicondylitis or tennis elbow is a frequent condition with long-lasting symptoms. In order to identify predictors for treatment success and pain in lateral epicondylitis, we used data from a randomized controlled trial. This trial investigated the efficacy of physiotherapy alone or combined with corticosteroid injection for acute lateral epicondylitis in general practice. METHODS: The outcomes treatment success and pain score on VAS were assessed at 6, 12, 26 and 52 weeks. We ran a univariate binary logistic regression with generalized estimating equations (GEE) and subsequently an adjusted multilevel logistic regression to analyze the association between potential prognostic indicators and the outcome success/ no success. To assess the changes in pain score we used a two-level multilevel linear regression (MLR) followed by an adjusted MLR model with random effects. RESULTS: The most consistent predictor for reduced treatment success at all time points was a high Pain Free Function Index score signifying more pain on everyday activities. Being on paid sick-leave and having a recurring complaint increased short term treatment success but gave decreased long-term treatment success. The patients reporting symptoms after engaging in probable overuse in an unusual activity, tended towards increased treatment success at all time-points, but significant only at 12 weeks. The most consistent predictor of increased pain at all time points was a higher overall complaints score at baseline. CONCLUSIONS: Our results suggest that in treating acute lateral epicondylitis, a consideration of baseline pain, a registration of the patient's overall complaint on a VAS scale and an assessment of the patient's perceived performance in everyday activities with the Pain Free Function Index can be useful in identifying patients that will have a more protracted and serious condition. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00826462 . Date of registration January 22, 2009. The Trial was prospectively registrated.

Gentamicin should remain part of the empirical sepsis regimen for adults. / Gentamicin bør fortsatt inngå i empirisk sepsisregime hos voksne.

In the Norwegian guidelines, the combination of a narrow-spectrum beta-lactam antibiotic and aminoglycoside should remain the first choice for empirical antibiotic therapy for the majority of severe infections.

Ibuprofen versus pivmecillinam for uncomplicated urinary tract infection in women-A double-blind, randomized non-inferiority trial.

BACKGROUND: Although uncomplicated urinary tract infections (UTIs) are often self-limiting, most patients will be prescribed antibiotic treatment. We assessed whether treatment with ibuprofen was non-inferior to pivmecillinam in achieving symptomatic resolution by day 4, with a non-inferiority margin of 10%. METHODS AND FINDINGS: This was a randomized, controlled, double-blind non-inferiority trial. We recruited patients from 16 sites in a general practice setting in Norway, Sweden, and Denmark. Non-pregnant women aged 18-60 years presenting with symptoms of uncomplicated UTI were screened for eligibility from 11 April 2013 to 22 April 2016. Patients with informed consent were randomized (1:1 ratio) to treatment with either 600 mg ibuprofen or 200 mg pivmecillinam 3 times a day for 3 days. The patient, treating physician, and study personnel were blinded to treatment allocation. The primary outcome was the proportion of patients who felt cured by day 4, as assessed from a patient diary. Secondary outcomes included the proportion of patients in need of secondary treatment with antibiotics and cases of pyelonephritis. A total of 383 women were randomly assigned to treatment with either ibuprofen (n = 194, 181 analyzed) or pivmecillinam (n = 189, 178 analyzed). By day 4, 38.7% of the patients in the ibuprofen group felt cured versus 73.6% in the pivmecillinam group. The adjusted risk difference with 90% confidence interval was 35% (27% to 43%) in favor of pivmecillinam, which crossed the prespecified non-inferiority margin. Secondary endpoints were generally in favor of pivmecillinam. After 4 weeks' follow-up, 53% of patients in the ibuprofen group recovered without antibiotic treatment. Seven cases of pyelonephritis occurred, all in the ibuprofen group, giving a number needed to harm of 26 (95% CI 13 to 103). Five of these patients were hospitalized and classified as having serious adverse events; 2 recovered as outpatients. A limitation of the study was the extensive list of exclusion criteria, eliminating almost half of the patients screened. We did not register symptoms in the screening process; hence, we do not know the symptom burden for those who declined to participate. This might make our results less generalizable. CONCLUSIONS: Ibuprofen was inferior to pivmecillinam for treating uncomplicated UTIs. More than half of the women in the ibuprofen group recovered without antibiotics. However, pyelonephritis occurred in 7 out of 181 women using ibuprofen. Until we can identify those women who will develop complications, we cannot recommend ibuprofen alone as initial treatment to women with uncomplicated UTIs. TRIAL REGISTRATION: ClinicalTrials.gov NCT01849926 EU Clinical Trials Register (EU-CTR), EudraCT Number 2012-002776-14.

Clinical and bacteriological efficacy of pivmecillinam treatment for uncomplicated urinary tract infections caused by ESBL-producing Escherichia coli: a prospective, multicentre, observational cohort study.

Objectives: To compare the clinical and bacteriological outcomes of pivmecillinam treatment for community-acquired urinary tract infections (UTIs) caused by ESBL-producing Escherichia coli versus non-ESBL-producing E. coli in an outpatient setting. Methods: A prospective, multicentre, observational cohort study of women aged ≥16 years, with pivmecillinam-treated community-acquired UTIs caused by E. coli with or without ESBL production, recruited from primary care, was conducted in the period from April 2013 to August 2016. Eighty-eight women (mean age 49.4 years) with community-acquired UTIs caused by ESBL-producing E. coli were compared with a control group of 74 women (mean age 50.1 years). Trial registration: Regional Committees for Medical and Health Research Ethics (REC) in Norway, ID 2011/2214, and ClinicalTrials.gov, ID NCT01531023. Results: The median time until symptom resolution after treatment initiation was 5 days for the ESBL cases and 3 days for the non-ESBL controls (P < 0.01). The proportion of women warranting a second antibiotic prescription in the follow-up period was higher for the ESBL cases [30/88 (34.1%) versus 10/72 (13.9%), P < 0.01]. Persistent bacteriuria was non-significantly more common among ESBL cases than in the control group [15/81 (18.5%) versus 6/67 (9.0%), P = 0.10]. A pivmecillinam dosage of 200 mg given three times daily for ≤5 days was associated with treatment failure (OR 4.77, 95% CI 1.40-19.44, P = 0.03) for the ESBL E. coli group. For the subgroup treated with 400 mg of pivmecillinam given three times daily there was no significantly increased OR for treatment failure between ESBL cases and the control group irrespective of treatment duration. Conclusions: Pivmecillinam given at 400 mg three times daily gave comparable clinical and bacteriological cure rates in women with community-acquired E. coli UTIs irrespective of ESBL production.

Predictors of Symptom Duration and Bacteriuria in Uncomplicated Urinary Tract Infection.

OBJECTIVE: To identify baseline predictors of symptom duration after empirical treatment for uncomplicated urinary tract infection (UTI) and significant bacteriuria in a cohort of women treated for UTI. DESIGN: Prospective single-centre cohort study. SETTING: Outpatient clinic in Norway. PATIENTS: From September 2010 to November 2011, 441 women aged 16-55 years with symptoms of uncomplicated UTI were included. RESULTS: Dipstick findings of leukocyte esterase 1 + (incidence rate ratio (IRR) 1.93, 95% confidence interval (CI) 1.23-3.01, p < 0.01) and microbe resistant to mecillinam treatment (IRR 1.41, 95% CI 1.07-1.89, p = 0.02) predicted longer symptom duration. More pronounced symptoms did not predict longer symptom duration (IRR 1.18, 95% CI 0.94-1.46, p = 0.15) or significant bacteriuria (odds ratio [OR] 1.16, 95% CI 0.72-1.88, p = 0.54). Leukocyte esterase 2 + (OR 2.51, 95% CI 0.92-6.83, p = 0.07) or 3 + (OR 2.40, 95% CI 0.88-6.05, p = 0.09) and nitrite positive urine dipstick test (OR 3.22, 95% CI 1.58-7.01, p = <0.01) were associated with bacteriuria. CONCLUSION: More pronounced symptoms did not correlate with significant bacteriuria or symptom duration after empirical treatment for acute cystitis. One might reconsider the current practice of treating uncomplicated UTI based on symptoms alone. Key Points Treatment strategies for milder infectious diseases must consider ways of reducing antibiotic consumption to decelerate the increase in antibiotic resistance. Our findings suggest that more emphasis should be put on urine dipstick results and bacteriological findings in the clinical setting. One might reconsider the current practice of treating uncomplicated UTIs based on symptoms alone.

Clinical features and inflammatory markers in pediatric pneumonia: a prospective study.

In this prospective, observational study on previously healthy children <18 years, we aimed to study the diagnostic ability of clinical features and inflammatory markers to (i) predict pathologic chest radiography in suspected pneumonia and (ii) differentiate etiology in radiological proven pneumonia. In 394 cases of suspected pneumonia, 265 (67%) had radiographs consistent with pneumonia; 34/265 had proof of bacterial etiology. Of the cases, 86.5% had received pneumococcal conjugate vaccine. In suspected pneumonia, positive chest radiography was significantly associated with increasing C-reactive protein (CRP) values, higher age, and SpO2 ≤92% in multivariate logistic regression, OR 1.06 (95% CI 1.03 to 1.09), OR 1.09 (95% CI 1.00 to1.18), and OR 2.71 (95% CI 1.42 to 5.18), respectively. In proven pneumonia, bacterial pneumonia was significantly differentiated from viral/atypical pneumonia by increasing CRP values and SpO2 >92% in multivariate logistic regression, OR 1.09 (95% CI 1.05 to 1.14) and OR 0.23 (95% CI 0.06 to 0.82), respectively. Combining high CRP values (>80 mg/L) and elevated white blood cell (WBC) count provided specificity >85%, positive likelihood ratios >3, but sensitivity <46% for both radiographic proven and bacterial pneumonia. CONCLUSION: With relatively high specificity and likelihood ratio CRP, WBC count and hypoxemia may be beneficial in ruling in a positive chest radiograph in suspected pneumonia and bacterial etiology in proven pneumonia, but with low sensitivity, the clinical utility is limited. What is Known: • Pneumonia is recommended to be a clinical diagnosis, and neither clinical features nor inflammatory markers can reliably distinguish etiology. • The etiology of pneumonia has changed after routine pneumococcal conjugate vaccine. What is New: • High CRP and WBC counts were associated with infiltrates in children with suspected pneumonia and with bacterial infection in proven pneumonia. • In the post-pneumococcal vaccination era, viral etiology is expected, and in cases of pneumonia with low CRP and WBC counts, a watch-and-wait strategy for antibiotic treatment may be applied.

Symptom load and general function among patients with erythema migrans: a prospective study with a 1-year follow-up after antibiotic treatment in Norwegian general practice.

OBJECTIVE: Promptly treated erythema migrans (EM) has good prognosis. However, some patients report persistent symptoms. Do patients with EM have more symptoms than the general population? We describe individual symptoms and general function in EM-patients at time of diagnosis and one year after treatment. DESIGN: Prospective study with 1-year follow up after treatment. Questionnaires included a modified version of the Subjective Health Complaints Inventory, comprising three additional Lyme borreliosis (LB) related symptoms. General function was assessed using a five-point scale modified from the COOP/WONCA charts. SETTING: Norwegian general practice. SUBJECTS: A total of 188 patients were included in a randomized controlled trial comparing three antibiotic regimens for EM, of whom 139 had complete data for this study. MAIN OUTCOME MEASURES: Individual symptoms, symptom load and general function. RESULTS: Mild symptoms were common, reported by 84.9% at baseline and by 85.6% at follow-up. At baseline, patients reported a mean of 5.4 symptoms, compared with 6.2 after one year. Severely bothersome symptoms and severely impaired general function were rare. Tiredness was the most reported symptom both at baseline and at follow-up. Palsy (other than facial) was the least reported symptom, but the only one with a significant increase. However, this was not associated to the EM. CONCLUSION: The symptom load was comparable to that reported in the general population. We found an increase in symptom load at follow-up that did not significantly affect general function. IMPLICATION: Monitoring patients' symptom loads prior to treatment reduce the probability of attributing follow-up symptoms to LB. Key points Erythema migrans has a good prognosis.Patients treated for erythema migrans have a slight increase in symptom load one year after treatment. This increase does not affect general function. The levels of subjective health complaints in patients treated for erythema migrans are comparable to the background population.

Antibiotic use and infections in nursing homes. / Antibiotikabruk og infeksjoner i sykehjem.

BACKGROUND: Residents in nursing homes have a higher risk of developing infections that require antibiotic treatment than elderly people living at home. Use of antibiotics may cause adverse effects and result in the development of antimicrobial resistance. MATERIAL AND METHOD: Data on healthcare-associated infections and antibiotic use in 540 Norwegian nursing homes were retrieved from the Norwegian Institute of Public Health's point prevalence survey in the spring of 2016. Based on information on drug, dosage and indication, we assessed whether the use of antibiotics for the treatment of UTIs was in accordance with the National Guidelines for the Use of Antibiotics in Primary Care. RESULTS: UTI was the most commonly occurring type of infection, with a prevalence of 2.7 %. Prescription of first-line antibiotics accounted for approximately 60 % of the prescriptions for treatment of this illness. Choice of drug, dosage and microbiological testing when treating lower UTIs was not always in accordance with the national guidelines. The study showed widespread use of methenamine in Norwegian nursing homes. INTERPRETATION: The survey indicates that compliance with the national guidelines when treating lower UTIs could be improved with regard to the choice of drug, dosage and microbiological testing. Norwegian nursing home doctors should also consider whether their use of methenamine is in accordance with national and international recommendations.

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.

General practitioners' and students' experiences with feedback during a six-week clerkship in general practice: a qualitative study.

OBJECTIVE: Feedback may be scarce and unsystematic during students' clerkship periods. We wanted to explore general practitioners' (GPs) and medical students' experiences with giving and receiving supervision and feedback during a clerkship in general practice, with a focus on their experiences with using a structured tool (StudentPEP) to facilitate feedback and supervision. DESIGN: Qualitative study. SETTING: Teachers and students from a six-week clerkship in general practice for fifth year medical students were interviewed in two student and two teacher focus groups. SUBJECTS: 21 GPs and nine medical students. RESULTS: We found that GPs first supported students' development in the familiarization phase by exploring the students' expectations and competency level. When mutual trust had been established through the familiarization phase GPs encouraged students to conduct their own consultations while being available for supervision and feedback. Both students and GPs emphasized that good feedback promoting students' professional development was timely, constructive, supportive, and focused on ways to improve. Among the challenges GPs mentioned were giving feedback on behavioral issues such as body language and insensitive use of electronic devices during consultations or if the student was very insecure, passive, and reluctant to take action or lacked social or language skills. While some GPs experienced StudentPEP as time-consuming and unnecessary, others argued that the tool promoted feedback and learning through mandatory observations and structured questions. CONCLUSION: Mutual trust builds a learning environment in which supervision and feedback may be given during students' clerkship in general practice. Structured tools may promote feedback, reflection and learning. Key Points Observing the teacher and being supervised are essential components of Medical students' learning during general practice clerkships. Teachers and students build mutual trust in the familiarization phase. Good feedback is based on observations, is timely, encouraging, and instructive. StudentPEP may create an arena for structured feedback and reflection.

Antibiotic resistance patterns of bacteria causing urinary tract infections in the elderly living in nursing homes versus the elderly living at home: an observational study.

BACKGROUND: Antibiotic resistance is a problem in nursing homes. Presumed urinary tract infections (UTI) are the most common infection. This study examines urine culture results from elderly patients to see if specific guidelines based on gender or whether the patient resides in a nursing home (NH) are warranted. METHODS: This is a cross sectional observation study comparing urine cultures from NH patients with urine cultures from patients in the same age group living in the community. RESULTS: There were 232 positive urine cultures in the NH group and 3554 in the community group. Escherichia coli was isolated in 145 urines in the NH group (64%) and 2275 (64%) in the community group. There were no clinically significant differences in resistance. Combined, there were 3016 positive urine cultures from females and 770 from males. Escherichia coli was significantly more common in females 2120 (70%) than in males 303 (39%) (p < 0.05). Enterococcus faecalis was significantly less common in females 223 (7%) than males 137 (18%) (p < 0.05). For females, there were lower resistance rates to ciprofloxacin among Escherichia coli (7% vs 12%; p < 0.05) and to mecillinam among Proteus mirabilis (3% vs 12%; p < 0.05). CONCLUSIONS: Differences in resistance rates for patients in the nursing home do not warrant separate recommendations for empiric antibiotic therapy, but recommendations based on gender seem warranted.