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Lakartidningen Aug 2020
Topics: Amdinocillin Pivoxil; Humans; Pyelonephritis
PubMed: 32852775
DOI: No ID Found -
Euro Surveillance : Bulletin Europeen... May 2023IntroductionEmpirical therapy for the treatment of urinary tract infections should be tailored to the current distribution and susceptibility of potential pathogens to...
IntroductionEmpirical therapy for the treatment of urinary tract infections should be tailored to the current distribution and susceptibility of potential pathogens to ensure optimal treatment.AimWe aimed to provide an up-to-date overview of the epidemiology and susceptibility of Enterobacterales isolated from urine in Germany.MethodsWe retrospectively analysed antimicrobial susceptibility data from 201,152 urine specimens collected between January 2016 and June 2021 from in- and outpatients. Multiple logistic regression analysis was used to evaluate the association between year of investigation and antibiotic resistance, adjusted for age, sex and species subgroup. Subgroup analyses were performed for midstream urine samples obtained from (i) female outpatients aged 15 to 50 years, (ii) female outpatients older than 50 years and (iii) male outpatients.ResultsResistance rates of less than 20% were observed for nitroxoline (3.9%), fosfomycin (4.6%), nitrofurantoin (11.7%), cefuroxime (13.5%) and ciprofloxacin (14.2%). Resistance to trimethoprim/sulfamethoxazole (SXT) (20.1%), amoxicillin-clavulanic acid (20.5%), trimethoprim (24.2%), pivmecillinam (29.9%) and ampicillin (53.7%) was considerably higher. In the subgroup of outpatient women aged 15-50 years, resistance rates were generally lower. Resistance rates of all antibiotics decreased from 2016 to 2021. Multiple logistic regression revealed the lowest adjusted odds ratio (ORadj) of 0.838 (95% confidence interval (CI): 0.819-0.858; p < 0.001) for pivmecillinam and the highest ORadj of 0.989 (95% CI: 0.972-1.007; p = 0.226) for nitrofurantoin.ConclusionsResistance has generally decreased over the past years, independent of sex, age and causative pathogen. Our data provide an important basis for empirical antibiotic recommendations in various settings and patient collectives.
Topics: Female; Male; Humans; Anti-Bacterial Agents; Nitrofurantoin; Amdinocillin Pivoxil; Retrospective Studies; Escherichia coli; Drug Resistance, Bacterial; Urinary Tract Infections; Trimethoprim, Sulfamethoxazole Drug Combination; Germany; Microbial Sensitivity Tests; Escherichia coli Infections
PubMed: 37166759
DOI: 10.2807/1560-7917.ES.2023.28.19.2200568 -
The Journal of Antimicrobial... Mar 2024Treatment options for urinary tract infections (UTIs) caused by ESBL-producing Enterobacterales are limited. Moreover, evidence to support therapeutic decisions is...
OBJECTIVES
Treatment options for urinary tract infections (UTIs) caused by ESBL-producing Enterobacterales are limited. Moreover, evidence to support therapeutic decisions is lacking. This study assessed current treatment strategies and patient and pathogen characteristics in relation to clinical and microbiological outcomes.
METHODS
Patients with UTI caused by ESBL-producing Enterobacterales were prospectively recruited by investigators at 15 infectious disease hospital departments. Data were collected on patient characteristics, treatments, clinical and microbiological cure 10-14 days after the end of treatment, and relapse within 3 months. Bacterial isolates were subjected to MIC determination and WGS.
RESULTS
In total, 235 patients (107 febrile UTI, 128 lower UTI) caused by Escherichia coli (n = 223) and Klebsiella spp. (n = 12) were included. Clinical and microbiological cure rates were 83% and 64% in febrile UTI, and 79% and 65% in lower UTI. Great variability in treatments was observed, especially in oral therapy for febrile UTI. No difference was seen in clinical outcomes with piperacillin/tazobactam (n = 28) compared with carbapenems (n = 41). Pivmecillinam was frequently used in lower UTI (n = 62), and was also associated with high clinical cure rates when used as initial therapy (10/10) or follow-up (7/8) for febrile UTI. Recurrent infection, diabetes mellitus and urogenital disease were associated (P < 0.05) with clinical failure and relapse. In E. coli, ST131 was significantly associated with relapse, and haemolysin with microbiological failure or relapse.
CONCLUSIONS
Antibiotic treatments were highly variable. Patient and pathogen factors were identified as potential determinants of disease presentation and outcomes and may prove useful to guide individualized treatment and follow-up.
Topics: Humans; Amdinocillin Pivoxil; Escherichia coli; Fever; Gammaproteobacteria; Prospective Studies; Recurrence; Urinary Tract Infections
PubMed: 38197416
DOI: 10.1093/jac/dkad402 -
Trials Sep 2023Oral treatment alternatives for febrile urinary tract infections are limited in the era of increasing antimicrobial resistance. We aim to evaluate if the combination of...
BACKGROUND
Oral treatment alternatives for febrile urinary tract infections are limited in the era of increasing antimicrobial resistance. We aim to evaluate if the combination of pivmecillinam and amoxicillin/clavulanic acid is non-inferior to current alternatives for step-down therapy in adult patients with febrile urinary tract infection.
METHODS
We plan to perform an investigator-initiated non-inferiority trial. Adult hospitalised patients treated with 1-5 days of intravenous antibiotics for acute febrile urinary tract infection caused by extended spectrum beta-lactamase (ESBL) producing Enterobacterales will be randomised 1:1 to either control (7-10 days of either oral ciprofloxacin 500 mg twice daily or oral trimethoprim-sulfamethoxazole 800 mg/160 mg twice daily or intravenous ertapenem 1 g once daily, depending on sex, drug allergy, glomerular filtration rate and susceptibility testing) or intervention (10 days of pivmecillinam 400 mg three times daily and amoxicillin/clavulanic acid 500/125 mg three times daily). The primary outcome will be clinical cure 10 days (+/- 2 days) after antibiotic treatment completion. Clinical cure is defined as being alive with absence of fever and return to non-infected baseline of urinary tract symptoms without additional antibiotic treatment or re-hospitalisation (for urinary tract infection) based on a centralised allocation-blinded structured telephone interview. We plan to recruit 330 patients to achieve 90% power based on a sample size simulation analysis using a two-group comparison, one-sided alpha of 2.5%, an absolute non-inferiority margin of 10% and expecting 93% clinical cure rate and 10% loss to follow-up. The primary endpoint will be analysed using generalised estimated equations and reported as risk difference for both intention-to-treat and per protocol populations. Patients are planned to be recruited from at least 10 centres in Sweden from 2023 to 2026.
DISCUSSION
If the combination of pivmecillinam and amoxicillin/clavulanic acid is found to be non-inferior to the control drugs there are potential benefits in terms of tolerability, frequency of interactions, outpatient treatment, side effects, nosocomial infections and drive for further antimicrobial resistance compared to existing drugs.
TRIAL REGISTRATION
NCT05224401. Registered on February 4, 2022.
Topics: Adult; Humans; Amoxicillin-Potassium Clavulanate Combination; Amdinocillin Pivoxil; Anti-Bacterial Agents; Urinary Tract Infections; Clavulanic Acid; Fever
PubMed: 37660037
DOI: 10.1186/s13063-023-07542-3 -
International Journal of Infectious... May 2017To compare the efficacy and safety of different pivmecillinam (PIV) regimes for uncomplicated lower urinary tract infections (UTIs). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To compare the efficacy and safety of different pivmecillinam (PIV) regimes for uncomplicated lower urinary tract infections (UTIs).
METHODS
The MEDLINE, Embase, and Cochrane Library databases were searched. Randomized controlled clinical trials (RCTs) involving adults or children with symptoms suggestive of uncomplicated UTI and that compared different PIV regimes or PIV versus other antibiotics were included. Meta-analyses were conducted to obtain direct and indirect efficacy estimates. PIV regimes were categorized into high total dosage, moderate total dosage, and low total dosage. The risk of bias was evaluated using the Cochrane tool.
RESULTS
Twenty-four RCTs were identified. No difference in clinical cure was found for the high vs. moderate (short-term: risk ratio (RR) 1.01, p=0.813; long term: RR 1.09, p=0.174) or high vs. low dosage comparisons (mean difference 0, 95% confidence interval -0.44 to 0.45, p=1). For bacteriological cure, comparisons of high vs. moderate dosage (short term: RR 1.05, p=0.056; long term: RR 1.05, p=0.131) and high vs. low dosage (short term: RR 1.02, p=0.759; long term: RR 1.13, p=0.247) showed a trend in favor of the high dosage treatment. Results for relapse, re-infection, and failure were inconclusive and not statistically significant. Patients treated with high dosages were 40% (p=0.062) and 44% (p=0.293) more likely to report mild to moderate adverse events.
CONCLUSIONS
There is insufficient evidence to support the use of an optimal combination of dosage, frequency, and duration of PIV therapy for the treatment of uncomplicated lower UTI. Evidence is limited due to the high risk of bias, poor reporting, and heterogeneous study data.
Topics: Amdinocillin Pivoxil; Anti-Infective Agents, Urinary; Dose-Response Relationship, Drug; Drug Administration Schedule; Humans; Urinary Tract Infections
PubMed: 28341436
DOI: 10.1016/j.ijid.2017.03.012 -
EClinicalMedicine Jul 2019To investigate if a 5-day course pivmecillinam (amdinocillin pivoxil) 400 mg three times daily is superior to a 3-day course in women with uncomplicated urinary tract...
Three versus five days of pivmecillinam for community-acquired uncomplicated lower urinary tract infection: A randomised, double-blind, placebo-controlled superiority trial.
BACKGROUND
To investigate if a 5-day course pivmecillinam (amdinocillin pivoxil) 400 mg three times daily is superior to a 3-day course in women with uncomplicated urinary tract infection (UTI).
METHODS
A randomised, double-blind, placebo-controlled trial conducted at nine primary care centres in Denmark. 368 women (18-70 years) with symptoms compatible with UTI were randomised to blinded therapy of 5 days [5d] or 3 days followed by 2 days of placebo [3d] from May 2015 to November 2017. Clinical data were assessed using a validated questionnaire at inclusion (day-0), daily the following 7 days and once again within the 2nd to 6th week after intervention. Bacteriological data were collected prior to intervention and twice between day 7 and 42. Main clinical endpoints were days to symptom resolution within 7 days after inclusion and proportions with clinical success at the end of intervention. Main bacteriological endpoint was proportion of participants with significant reduction of bacteriuria (≥ 10 CFU/mL) in 1st control urine sample. ClinicalTrialsRegister.eu: 2014-001321-32.
FINDINGS
180 (5d) and 188 (3d) participants were included in the study (mean age: 35.4 [5d] and 34.9 [3d]). Of these, 125 (70% [5d]) and 122 (66% [3d]) had a positive baseline urine culture. Forty-four participants were lost to follow-up, leaving 161 [5d] and 163 [3d] participants for analysis, respectively. Mean time to symptom resolution was 2.91 (SD 1.46; [5d]) days and 2.94 (SD 1.42; [3d]) days (P = .894). Clinical success at the end of treatment occurred for 117 of 153 (76%) receiving the 5d-course and for 115 of 157 (73%) receiving the 3d course (difference 3.2% [95% CI -7.1% - 13.5%]; P = .601). Bacteriological success was seen in 92 of 104 (88%) participants given the 5d course and in 86 of 99 (87%) given the 3d course (difference 1.6% [95% CI -8.4%-11.6%]; P = .895).
INTERPRETATIONS
A 5-day course of pivmecillinam was not superior to a 3-day course in clinical or bacteriological outcomes for UTI.
PRIMARY FUNDING SOURCE
The Danish Regions [no. 14/217].
PubMed: 31388664
DOI: 10.1016/j.eclinm.2019.06.009 -
Scandinavian Journal of Primary Health... Sep 2020To compare the proportion of therapy failure, recurrence and complications within 30 days after consultation between men diagnosed with lower urinary tract infection...
OBJECTIVE
To compare the proportion of therapy failure, recurrence and complications within 30 days after consultation between men diagnosed with lower urinary tract infection (UTI) treated with narrow-spectrum antibiotics (nitrofurantoin or pivmecillinam) and broad-spectrum antibiotics (fluoroquinolones or trimethoprim or trimethoprim/sulfamethoxazole).
DESIGN
A retrospective cohort study based on data derived from electronic medical records between January 2012 and December 2015.
SETTING
Primary health care and hospital care in five different counties in Sweden. A total of 16,555 men aged between 18 and 79 years diagnosed with lower UTI.
MAIN OUTCOME MEASURES
Treatment with narrow-spectrum antibiotics was compared with broad-spectrum antibiotics regarding therapy failure, recurrence and complications within 30 days.
RESULTS
The median age of included men was 65 IQR (51-72) years. Narrow-spectrum antibiotics were prescribed in 8457 (40%) and broad-spectrum antibiotics in 12,667 (60%) cases, respectively. Therapy failure was registered in 192 (0.9%), recurrence in 1277 (6%) and complications in 121 (0.6%) cases. Therapy failure and recurrence were more common in patients treated with narrow-spectrum antibiotics and trimethoprim ( < 0.001), but no such difference could be detected regarding complications.
CONCLUSION
There was no difference in incidence of complications within 30 days between men treated with narrow- or broad-spectrum antibiotics. Patients prescribed broad-spectrum antibiotics had lower odds of reconsultation because of therapy failure and recurrence. From current data, treatment with narrow-spectrum antibiotics seems to be an optimal choice regarding preventing complications when treating men with lower UTI. KEY POINTS Complications such as pyelonephritis and sepsis are uncommon in men diagnosed with lower urinary tract infection treated with antibiotics. There was no difference in incidence of complications among men diagnosed with lower urinary tract infection treated with narrow- or broad-spectrum antibiotics. In spite of higher incidence of therapy failure and recurrence, treatment with narrow-spectrum antibiotics seems to be an optimal choice regarding preventing complications when treating men diagnosed with lower UTI.
Topics: Adolescent; Adult; Aged; Amdinocillin Pivoxil; Anti-Bacterial Agents; Humans; Male; Middle Aged; Pyelonephritis; Retrospective Studies; Urinary Tract Infections; Young Adult
PubMed: 32686974
DOI: 10.1080/02813432.2020.1794409 -
PloS One 2019This study aimed to retrospectively assess the clinical outcome with nitrofurantoin and pivmecillinam for lower urinary tract infections (UTI) in men. Patients treated... (Clinical Trial)
Clinical Trial
OBJECTIVES
This study aimed to retrospectively assess the clinical outcome with nitrofurantoin and pivmecillinam for lower urinary tract infections (UTI) in men. Patients treated with trimethoprim were also included for comparison.
METHODS
All prescriptions of the study antibiotics to adult men in Uppsala County, Sweden, during 2012 were extracted. Data on patient characteristics, therapy, clinical outcome and microbiological results were obtained from the electronic medical records. The relative impact of antibiotic therapy, patient factors and pathogens on clinical outcome was assessed with univariate logistic regression using a 95% confidence interval (CI).
RESULTS
832 prescriptions were identified, and 171 patients treated with nitrofurantoin (n = 69), pivmecillinam (n = 57) and trimethoprim (n = 45) met the inclusion criteria. Treatment failure occurred in one patient treated with nitrofurantoin and in four patients treated with pivmecillinam. New prescriptions of UTI antibiotics and relapse within 3 months after completion of therapy were more frequent with nitrofurantoin (34% and 15%) and pivmecillinam (30% and 17%) than trimethoprim (22 and 7%). However, these differences were not statistically significant and substantial heterogeneity was noted between the treatment groups. Urinary tract catheterization was associated with a higher risk for new antibiotic prescriptions (OR 2.34, 95% CI 1.14-4.80; P = 0.022) and prostate cancer was associated with a higher incidence of relapse (OR 3.01, 95% CI 1.09-8.29; P = 0.042).
CONCLUSIONS
The clinical outcome with nitrofurantoin and pivmecillinam was acceptable in comparison with the results of previous studies. These antibiotics are suitable for empirical treatment of lower UTI in men considering their high activity against Escherichia coli and limited impact on the intestinal microbiota.
Topics: Adult; Aged; Aged, 80 and over; Amdinocillin Pivoxil; Escherichia coli; Escherichia coli Infections; Humans; Male; Middle Aged; Nitrofurantoin; Retrospective Studies; Urinary Tract Infections
PubMed: 30682092
DOI: 10.1371/journal.pone.0211098 -
Scandinavian Journal of Primary Health... Mar 2019The aim of this study was to describe and characterize the prescription of antibiotics for urinary tract infection (UTI) in general practice in Denmark and to evaluate...
OBJECTIVE
The aim of this study was to describe and characterize the prescription of antibiotics for urinary tract infection (UTI) in general practice in Denmark and to evaluate compliance with current recommendations.
DESIGN
National registry-based study Setting: Danish general practice Patients: 267.539 patients who redeemed a prescription for antibiotics with the clinical indication UTI at community pharmacies between July 1 2012 and June 31 2013.
MAIN OUTCOME MEASURES
Antibiotics prescribed for 1) acute lower UTI, 2) acute upper UTI and 3) recurrent UTI presented as amount of prescriptions, number of treatments per 1000 inhabitants per day (TID) and defined daily doses per 1000 inhabitants per day (DID).
RESULTS
A total of 507.532 prescriptions were issued to 267.539 patients during the one year study period, representing 2.35 DID. Acute lower UTI was the most common reason for prescription of antibiotics (89.5%) followed by recurrent UTI (8.4%). The majority of the prescriptions were issued to people above 60 year old (57.6%). Pivmecillinam was the most commonly prescribed antibiotic in acute lower (45.8%) and acute upper (63.3%) UTI. Trimethroprim was the most commonly prescribed antibiotic in recurrent UTI (45.9%). Prescription of quinolones increased with increasing patient-age (p = <.0001).
CONCLUSION
Compliance with current Danish recommendations was moderately high. Pivmecillinam is the first line antibiotic for the management of acute lower and upper UTI, and trimethroprim is the first line option of recurrent UTI. A high proportion of the antibiotic prescriptions were issued in the elderly population including a relatively high prescription rate of quinolones. Key points Urinary tract infection (UTI) is a common cause for prescription of antibiotics in general practice Poor compliance in general practice with recommendations for first-line treatment of UTI may increase antibiotic resistance Danish general practitioners are generally compliant with national and regional guidelines for antibiotic treatment of UTI There is high use of antibiotics in the elderly population including a worrisome high use of broad-spectrum antibiotics, such as Quinolones.
Topics: Adolescent; Adult; Age Factors; Aged; Aged, 80 and over; Amdinocillin Pivoxil; Anti-Bacterial Agents; Child; Child, Preschool; Denmark; Drug Prescriptions; Female; General Practice; General Practitioners; Guideline Adherence; Humans; Infant; Infant, Newborn; Male; Middle Aged; Practice Patterns, Physicians'; Quinolones; Urinary Tract Infections; Young Adult
PubMed: 30689491
DOI: 10.1080/02813432.2019.1569425