-
Lakartidningen Aug 2020
Topics: Amdinocillin Pivoxil; Humans; Pyelonephritis
PubMed: 32852775
DOI: No ID Found -
International Journal of Epidemiology Apr 2010Ciprofloxacin, ceftriaxone and pivmecillinam are the antibiotics currently recommended by the World Health Organization (WHO) for the treatment of dysentery in children;... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Ciprofloxacin, ceftriaxone and pivmecillinam are the antibiotics currently recommended by the World Health Organization (WHO) for the treatment of dysentery in children; yet there have been no reviews of the clinical effectiveness of these antibiotics in recent years.
METHODS
We reviewed all literature reporting the effect of ciprofloxacin, ceftriaxone and pivmecillinam for the treatment of dysentery in children in the developing countries. We used a standardized abstraction and grading format and performed meta-analyses to determine the effect of treatment with these antibiotics on rates of treatment failure, bacteriological failure and bacteriological relapse. The CHERG Standard Rules were applied to determine the final effect of treatment with these antibiotics on diarrhoea mortality.
RESULTS
Eight papers were selected for abstraction. Treatment with ciprofloxacin, ceftriaxone or pivmecillinam resulted in a cure rate of >99% while assessing clinical failure, bacteriological failure and bacteriological relapse.
CONCLUSIONS
The antibiotics recommended by the WHO--ciprofloxacin, ceftriaxone and pivmecillinam--are effective in reducing the clinical and bacteriological signs and symptoms of dysentery and thus can be expected to decrease diarrhoea mortality attributable to dysentery.
Topics: Amdinocillin Pivoxil; Anti-Bacterial Agents; Ceftriaxone; Child, Preschool; Ciprofloxacin; Dysentery; Dysentery, Bacillary; Female; Humans; Infant; Male; Randomized Controlled Trials as Topic; Salmonella Infections; Shigella dysenteriae; Treatment Outcome
PubMed: 20348130
DOI: 10.1093/ije/dyq024 -
British Journal of Clinical Pharmacology Jun 19771 The plasma concentration/time curves of ampicillin and mecillinam in normal subjects were measured after oral administration of ampicillin (500 mg) and pivmecillinam...
1 The plasma concentration/time curves of ampicillin and mecillinam in normal subjects were measured after oral administration of ampicillin (500 mg) and pivmecillinam (400 and 600 mg). 2 Similar plasma concentration/time curves of ampicillin and mecillinam in the starved normal subjects followed oral administration of ampicillin (500 mg) and pivmecillinam (600 mg). 3 The plasma concentration/time curve of mecillinam was measured in the same normal subjects after oral administration of pivmecillinam (400 mg) with a reproducible standardized Lundh test meal. 4 There was no statistically significant difference in the plasma concentration/time curve of mecillinam after pivmecillinam/400 mg) and the meal compared with the plasma concentration/time curve after oral pivmecillinam (400 mg) was given to the same subjects when starved. After administration of pivmecillinam (400 mg) with meal, Tasc was significantly delayed beyond the value obtained when the subjects were starved. 5 The pharmacokinetics of pivmecillinam in coeliac disease are normal. This finding contrasts with previous studies on the pharmacokinetics of another pivaloyloxymethylpenicillin ester, pivampicillin, in this condition.
Topics: Adolescent; Adult; Amdinocillin Pivoxil; Ampicillin; Biological Assay; Celiac Disease; Escherichia coli; Food; Humans; Intestinal Absorption; Kinetics; Middle Aged; Penicillanic Acid; Sarcina; Starvation
PubMed: 197981
DOI: 10.1111/j.1365-2125.1977.tb00711.x -
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 -
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 -
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 -
Antimicrobial Agents and Chemotherapy Apr 1988The bioavailability of amdinocillin was not altered when amdinocillin pivoxil was ingested 1 h before a standard breakfast, and it increased by 20% when amdinocillin...
The bioavailability of amdinocillin was not altered when amdinocillin pivoxil was ingested 1 h before a standard breakfast, and it increased by 20% when amdinocillin pivoxil was ingested with or 1 h after a standard breakfast. Amdinocillin pivoxil would be convenient for patients since it may be taken with or without food.
Topics: Administration, Oral; Adult; Amdinocillin; Amdinocillin Pivoxil; Biological Availability; Chromatography, High Pressure Liquid; Female; Food; Humans; Male; Middle Aged; Random Allocation
PubMed: 3377469
DOI: 10.1128/AAC.32.4.592 -
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