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%.
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.
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.
ClinicalTrials.gov NCT01849926 EU Clinical Trials Register (EU-CTR), EudraCT Number 2012-002776-14.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Hospitalization is potentially detrimental to nursing home patients and resource demanding for the specialist health care. This study assessed if a brief training program in administrating ...intravenous fluids and antibiotics in nursing homes could reduce hospital transfers and ensure high quality care locally.
A pragmatic and modified cluster randomized stepped-wedge trial with randomization on nursing home level.
330 cases in 296 nursing home residents from 30 nursing homes were included. Cases were patients provided intravenous antibiotics or intravenous fluids, in nursing home or hospital. Primary outcome was localization of treatment, secondary outcomes were number of days treated, days of hospitalization among admitted patients, type of antibiotics used and 30-day mortality.
The nursing homes sequentially received a one-day educational program for the health workers including theory and practical training in intravenous treatment of dehydration and infection, run by two skilled nurses. After completing the training program, the nursing homes had competence to provide intravenous treatment locally.
The intervention had a highly significant effect on treatment in nursing homes (OR 8.35, 2.08 to 33.6; P<0.01, or RR 2.23, 1.48 to 2.56). The number treated in nursing homes was stable over time; the number treated in hospital gradually decreased (chi square for trend P< 0.001). Among patients receiving intravenous antibiotics in the nursing homes, 50 (46%) died within 30 days, compared to 30 (36%) treated in the hospital (P = 0.19). Among patients receiving intravenous fluids locally, 21 (19%) died within 30 days, compared to 2 (8%) in the hospital group (P = 0.34). Mortality was associated with reduced consciousness and elevated c-reactive protein.
A brief educational program delivered to nursing home personnel was feasible and effective in reducing acute hospital admissions from nursing homes for treatment of dehydration and infections.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
When patented, brand-name antibiotics lose market exclusivity, generics typically enter the market at lower prices, which may increase consumption of the drug. To examine the effect of generic market ...entry on antibiotic consumption in the United States, we conducted an interrupted time series analysis of the change in the number of prescriptions per month for antibiotics for which at least one generic entered the US market between 2000 and 2012. Data were acquired from the IQVIA Xponent database. Thirteen antibiotics were analyzed. Here, we show that one year after generic entry, the number of prescriptions increased for five antibiotics (5 to 406%)-aztreonam, cefpodoxime, ciprofloxacin, levofloxacin, ofloxacin-and decreased for one drug: cefdinir. These changes were sustained two years after. Cefprozil, cefuroxime axetil and clarithromycin had significant increases in trend, but no significant level changes. No consistent pattern for antibiotic use following generic entry in the United States was observed.
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).
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.
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 (> 10
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).
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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.
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.
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.
Despite the urgent need for new, effective antibiotics, few antibiotics of value have entered the market during the past decades. Therefore, incentives have been developed to stimulate antibiotic ...R&D. For these incentives to be effective, geographic availability for recently approved antibiotics needs to be better understood. In this study, we analyze geographic availability and market introduction of antibiotics approved between 1999 and 2014.
We identified antibiotics, considered new chemical entities (NCEs) for systemic use approved globally between 1999 and 2014, from national medicine agencies' lists of approved drugs, and data from the WHO Collaborating Center for Drug Statistics. Geographic availability was mapped using sales data from IQVIA, and analyzed with regards to class, indication, safety, and origin.
Of the 25 identified NCEs, only 12 had registered sales in more than 10 countries. NCEs with the widest geographic availability had registered sales in more than 70 countries within a ten-year timeframe and 30 countries within a three-year timeframe, spreading across five different geographic regions and three country income classes. Half (52%) of the NCEs had an indication for infections caused by antibiotic- resistant bacteria, little diversity was seen regarding target pathogen and indication. Antibiotics originated from and/or marketed by companies from the US or Europe had greater geographic availability compared to Japanese antibiotics, which seldom reached outside of Asia. For 20 NCEs developers chose to fully or partially sublicense marketing rights to a number of companies of different sizes.
Our findings show great variation in geographic availability of antibiotics, indicating that availability in multiple regions and country income classes is possible, but rarely seen within a few years of market authorization. Sublicensing agreements between multiple companies was common practice. Moreover, differences were seen between countries regarding benefit/risk evaluations and company behavior. These findings could be a potential source of uncertainties, and create barriers to assure that working antibiotics are developed and made available according to public health needs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Inappropriate antibiotic prescribing, particularly for respiratory tract infections (RTI) in ambulatory care, has become a worldwide public health threat due to resulting antibiotic resistance. In ...spite of various interventions and campaigns, wide variations in antibiotic use persist between European countries. Cultural determinants are often referred to as a potential cause, but are rarely defined. To our knowledge, so far no systematic literature review has focused on cultural determinants of antibiotic use. The aim of this study was to identify cultural determinants, on a country-specific level in ambulatory care in Europe, and to describe the influence of culture on antibiotic use, using a framework of cultural dimensions.
A computer-based systematic literature review was conducted by two research teams, in France and in Norway. Eligible publications included studies exploring antibiotic use in primary care in at least two European countries based on primary study results, featuring a description of cultural determinants, and published between 1997 and 2015. Quality assessment was conducted independently by two researchers, one in each team, using appropriate checklists according to study design. Each included paper was characterized according to method, countries involved, sampling and main results, and cultural determinants mentioned in each selected paper were extracted, described and categorized. Finally, the influence of Hofstede's cultural dimensions associated with antibiotic consumption within a primary care setting was described.
Among 24 eligible papers, 11 were rejected according to exclusion criteria. Overall, 13 papers meeting the quality assessment criteria were included, of which 11 used quantitative methods and two qualitative or mixed methods. The study participants were patients (nine studies) and general practitioners (two studies). This literature review identified various cultural determinants either patient-related (illness perception/behaviour, health-seeking behaviour, previous experience, antibiotic awareness, drug perception, diagnosis labelling, work ethos, perception of practitioner) or practitioner-related (RTI management, initial training, antibiotic awareness, legal issues, practice context) or both (antibiotic awareness).
Cultural factors should be considered as exerting an ubiquitous influence on all the consecutive stages of the disease process and seem closely linked to education. Interactions between determinant categories, cultural dimensions and antibiotic use in primary care are multiple, complex and require further investigation within overlapping disciplines. The context of European projects seems particularly relevant.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
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.
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.
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.
ClinicalTrials.gov Identifier: NCT00826462 . Date of registration January 22, 2009. The Trial was prospectively registrated.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
PDF
