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Antimicrobial Agents and Chemotherapy Jan 2005The knowledge of the effects of antimicrobial agents on the normal vaginal microflora is limited. The objective of the present study was to study the ecological impact...
The knowledge of the effects of antimicrobial agents on the normal vaginal microflora is limited. The objective of the present study was to study the ecological impact of pivmecillinam on the normal vaginal microflora. In 20 healthy women, the estimated day of ovulation was determined during three subsequent menstrual cycles. Microbiological and clinical examinations were performed on the estimated day of ovulation and on day 3 in all cycles and also on day 7 after ovulation in cycles 1 and 2. Anaerobic and facultative anaerobic gram-positive rods, mainly species of lactobacilli and actinomycetes, dominated the microflora. One woman was colonized on the third day of administration with a resistant Escherichia coli strain, and Candida albicans was detected in one woman on days 3 and 7 in cycle 2. No other major changes in the normal microflora occurred during the study. Administration of pivmecillinam had a minor ecological impact on the normal vaginal microflora.
Topics: Actinobacteria; Administration, Oral; Adult; Amdinocillin Pivoxil; Anti-Bacterial Agents; Bacteria, Aerobic; Bacteria, Anaerobic; Ecosystem; Female; Humans; Lactobacillus; Menstruation; Vagina
PubMed: 15616292
DOI: 10.1128/AAC.49.1.170-175.2005 -
Scandinavian Journal of Primary Health... Mar 2007To analyse associations between symptoms and bacteriuria in uncomplicated lower urinary tract infection in women (LUTIW) and to evaluate outcome of therapy with three... (Comparative Study)
Comparative Study Randomized Controlled Trial
Clinical and bacteriological outcome of different doses and duration of pivmecillinam compared with placebo therapy of uncomplicated lower urinary tract infection in women: the LUTIW project.
OBJECTIVE
To analyse associations between symptoms and bacteriuria in uncomplicated lower urinary tract infection in women (LUTIW) and to evaluate outcome of therapy with three different regimens of pivmecillinam or placebo.
DESIGN
Prospective, multicentre, randomized, double-blind, and placebo-controlled therapy study. Symptoms registered at inclusion, during therapy and at follow-up visits after 8-10 and 35-49 days. Significant bacteriuria defined according to current European guidelines.
SETTING
A total of 18 primary healthcare centres in northern Sweden. Subjects. Women aged 18 years and above with symptoms of urgency, dysuria, supra pubic or loin pain. Main outcome measures. Symptoms and bacteriuria at inclusion and course of symptoms, bacteriuria, and their combinations during and post-therapy.
RESULTS
At inclusion, no associations or significant differences were found between symptom scores and bacteriuria, bacterial counts, or species. The 884 patients (77%) with significant bacteriuria were followed up. All pivmecillinam therapies were superior to placebo (p < 0.001). From day six until first follow-up, the mean values of all symptoms were higher and the bacteriological cure was lower at first follow-up in the three days (84%) compared with the seven days regimens (93-94%, p < 0.001). At final follow-up clinical cure was similar in all pivmecillinam regimens (65-72%) as was bacteriological cure (83-89%). Pivmecillinam had few low to mild adverse reactions, comparable to placebo.
CONCLUSIONS
Symptoms are not conclusive for diagnosis of LUTIW. Pivmecillinam therapies are superior to placebo and seven days regimens are more efficient than three days. Pivmecillinam 200 mg x 2 x 7 days is recommended as a first-line therapy for LUTIW.
Topics: Adolescent; Adult; Aged; Amdinocillin Pivoxil; Anti-Bacterial Agents; Anti-Infective Agents, Urinary; Bacteriuria; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Male; Middle Aged; Prospective Studies; Time Factors; Treatment Outcome; Urinary Tract Infections
PubMed: 17354160
DOI: 10.1080/02813430601183074 -
PLoS Medicine May 2018Although uncomplicated urinary tract infections (UTIs) are often self-limiting, most patients will be prescribed antibiotic treatment. We assessed whether treatment with... (Comparative Study)
Comparative Study Randomized Controlled 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.
Topics: Adult; Amdinocillin Pivoxil; Anti-Infective Agents, Urinary; Anti-Inflammatory Agents, Non-Steroidal; Double-Blind Method; Female; Humans; Ibuprofen; Urinary Tract Infections
PubMed: 29763434
DOI: 10.1371/journal.pmed.1002569 -
Antimicrobial Agents and Chemotherapy Mar 1984A total of 158 volunteers each received 21 repeated oral doses of 500 mg of cefuroxime axetil (CAE) during four comparative cross-over trials. Pharmacokinetics were...
A total of 158 volunteers each received 21 repeated oral doses of 500 mg of cefuroxime axetil (CAE) during four comparative cross-over trials. Pharmacokinetics were studied in 8 volunteers (CAE versus ampicillin), relative bioavailability and tolerance were studied in 100 volunteers (CAE versus pivmecillinam and CAE versus pivampicillin), and tolerance alone was studied in 50 volunteers (CAE versus ampicillin). Overall, urinary recoveries of the active antibiotics ranked absorption of the drugs in the order least to greatest: pivmecillinam, ampicillin, CAE, and pivampicillin. The pharmacokinetics of CAE and ampicillin did not change after repeated dosing. Peak serum levels of cefuroxime were significantly higher than those of ampicillin after doses 1 and 21 but the urinary recoveries of both antibiotics were around 35% of the dose. CAE was as well tolerated as ampicillin but there were smaller numbers of episodes of fluid bowel motions on pivmecillinam and pivampicillin than on CAE, which may have been due to the smaller amounts of active antibiotic in the doses of the pivaloyloxymethyl esters.
Topics: Adolescent; Adult; Amdinocillin Pivoxil; Ampicillin; Biological Availability; Cefuroxime; Cephalosporins; Chromatography, High Pressure Liquid; Enzymes; Female; Humans; Kinetics; Male; Middle Aged
PubMed: 6721467
DOI: 10.1128/AAC.25.3.344 -
British Heart Journal Dec 1995To study the effect of induced carnitine depletion on myocardial structure and function.
OBJECTIVE
To study the effect of induced carnitine depletion on myocardial structure and function.
SUBJECTS AND DESIGN
7 healthy adult volunteers given 1200 mg pivmecillinam per day for 7-8 weeks were studied by echocardiography before and after 7-8 weeks of treatment and a 15 months follow up after the treatment period.
SETTING
Teaching hospital.
MAIN OUTCOME MEASURES
Carnitine concentration in serum, urine, and muscle and echocardiographic measurements.
RESULTS
After 7-8 weeks of treatment the median free serum carnitine concentration was reduced to 7% and the median total muscle carnitine concentration to 46% of the pretreatment levels. The median diastolic interventricular septum thickness decreased by 14% (mean 26%, P = 0.028) and the median left ventricular mass by 10% (mean 20%, P = 0.018). Fifteen months later these dimensions had increased but not completely returned to pretreatment values.
CONCLUSIONS
Extended treatment with pivalic acid containing antibiotics causes carnitine depletion which may lead to changes in cardiac structure.
Topics: Adolescent; Adult; Amdinocillin Pivoxil; Anti-Bacterial Agents; Carnitine; Echocardiography; Female; Heart Septum; Humans; Male; Middle Aged; Muscle, Skeletal; Myocardium; Pentanoic Acids; Time Factors
PubMed: 8541173
DOI: 10.1136/hrt.74.6.656 -
MicrobiologyOpen Dec 2019Pivmecillinam (amdinocillin pivoxil) is the recommended first-choice antibiotic used to treat urinary tract infections (UTIs) in Denmark. The frequency of mutation to...
Pivmecillinam (amdinocillin pivoxil) is the recommended first-choice antibiotic used to treat urinary tract infections (UTIs) in Denmark. The frequency of mutation to mecillinam (MEC) resistance is described as high in vitro; however, treatment of UTI has a good clinical response and prevalence of mecillinam resistance in Escherichia coli remains low despite many years of use. We describe occurrence of in vivo mecillinam resistance in a clinical isolate of ESBL-producing E. coli following pivmecillinam treatment. The identified phenotypic differences in the mecillinam resistant isolate compared with the original mecillinam susceptible isolate were a full-length LPS with O-antigen (O25), mecillinam resistance and a lower MIC for ceftazidime. Regarding genotype, the resistant isolate differed with a mutation in bla to bla , loss of a part of a plasmid and a genomic island, respectively, and insertion of a transposase in wbbL, causing the rough phenotype. The observed mecillinam resistance is expected to be caused by the mutation in bla with additional contribute from the serotype shift. We continue to recommend the use of pivmecillinam as first-line treatment for UTI.
Topics: Amdinocillin; Amdinocillin Pivoxil; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Genome, Bacterial; Genomics; Humans; Microbial Sensitivity Tests; Multilocus Sequence Typing; Mutation; Phylogeny; Whole Genome Sequencing; beta-Lactamases
PubMed: 31573735
DOI: 10.1002/mbo3.941 -
British Journal of Clinical Pharmacology Aug 1976In a pharmacokinetic study in six volunteers peak serum mecillinam concentrations were proportional to the oral dose of pivmecillinam at two dose levels of 200 and 400...
In a pharmacokinetic study in six volunteers peak serum mecillinam concentrations were proportional to the oral dose of pivmecillinam at two dose levels of 200 and 400 mg. Effects of bed rest, probenecid and a 6 day course of treatment with pivmecillinam on serum mecillinam concentrations after an oral dose of pivmecillinam (two 200 mg capsules) have been investigated. Resting subjects had lower peak serum levels and a decreased rate of clearance than moderately active subjects, changes which are similar to those previously reported for benzylpenicillin. Pretreatment with probenecid produced significantly higher serum mecillinam levels, a longer serum antibiotic half-life and a decreased rate of drug clearance which suggests that mecillinam is actively excreted by kidney tubules. Plasma mecillinam level profiles obtained after the first dose of a 6 day treatment period were not significantly different from corresponding values after the first dose on the seventh day which indicates that each dose of mecillinam is eliminated in healthy young adults before succeeding doses are taken.
Topics: Absorption; Adult; Amdinocillin; Amdinocillin Pivoxil; Anti-Bacterial Agents; Half-Life; Humans; Male; Young Adult
PubMed: 22216505
DOI: 10.1111/j.1365-2125.1976.tb04886.x -
BMC Infectious Diseases Nov 2016The prevalence of urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae is increasing and the therapeutic options...
BACKGROUND
The prevalence of urinary tract infections (UTIs) caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae is increasing and the therapeutic options are limited, especially in primary care. Recent indications have suggested pivmecillinam to be a suitable option. This pilot study aimed to assess the viability of pivmecillinam as a therapeutic option in a Dublin cohort of mixed community and healthcare origin.
METHODS
A prospective measurement of mean and fractional inhibitory concentrations of antibiotic use in 95 patients diagnosed with UTI caused by ESBL-producing Enterobacteriaceae was carried out. 36 % patients were from general practice, 40 % were admitted to hospital within south Dublin, and 25 % samples arose from nursing homes. EUCAST breakpoints were used to determine if an isolate was sensitive or resistant to antibiotic agents.
RESULTS
Sixty-nine percent of patients (N = 66) with urinary ESBL isolates were female. The mean age of females was 66 years compared with a mean age of 74 years for males. Thirty-six percent of isolates originated from primary care, hospital inpatients (26 %), and nursing homes (24 %). The vast majority of ESBL isolates were E. coli (80 %). The E tests for mecillinam and co-amoxiclav had concentration ranges from 0.16 mg/L up to 256 mg/L. The mean inhibitory concentration (MIC) of mecillinam ranged from 0.25 to 256 mg/L, while co-amoxiclav MICs ranged from 6 to 256 mg/L. The percentage of isolates resistant to mecillinam and co-amoxiclav was found to be 5.26 and 94.74 % respectively.
CONCLUSIONS
This is the first study exploring the use of pivmecillinam in an Irish cohort and has demonstrated that its use in conjunction with or without co-amoxiclav is an appropriate and useful treatment for urinary tract infections caused by ESBL-producing organisms.
Topics: Aged; Amdinocillin; Amdinocillin Pivoxil; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Infections; Female; General Practice; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Hospitalization; Hospitals; Humans; Ireland; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Nursing Homes; Pilot Projects; Prevalence; Prospective Studies; Risk Factors; Urinary Tract Infections; beta-Lactamases
PubMed: 27806687
DOI: 10.1186/s12879-016-1797-3 -
Antimicrobial Agents and Chemotherapy Sep 2010An increase in extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli has been observed in outpatient settings. Consequently, 100 ESBL-positive E. coli...
An increase in extended-spectrum-beta-lactamase (ESBL)-producing Escherichia coli has been observed in outpatient settings. Consequently, 100 ESBL-positive E. coli isolates from ambulatory patients with clinically confirmed urinary tract infections were collected by a single laboratory between October 2004 and January 2008. Antimicrobial susceptibility testing was carried out using the oral antibiotics fosfomycin, pivmecillinam, and nitrofurantoin and the parenteral antibiotic ertapenem. Susceptibility rates indicate that fosfomycin (97%), nitrofurantoin (94%), and pivmecillinam (85%) could be considered important oral treatment options.
Topics: Amdinocillin Pivoxil; Anti-Bacterial Agents; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Nitrofurantoin; Urinary Tract Infections; beta-Lactamases
PubMed: 20585127
DOI: 10.1128/AAC.01760-09 -
Journal of Applied Microbiology 2005Mango bacterial black spot, caused by Xanthomonas campestris pv. mangiferaeindicae, is a potentially severe disease in several tropical and subtropical areas. Data...
AIMS
Mango bacterial black spot, caused by Xanthomonas campestris pv. mangiferaeindicae, is a potentially severe disease in several tropical and subtropical areas. Data describing the life cycle of the pathogen are needed for improving integrated pest management strategies. Because of the important bacterial microflora associated with mango leaves, isolation of the pathogen is often difficult using nonselective agar media.
METHODS AND RESULTS
A previously developed medium, BVGA, failed to inhibit several Gram-negative saprophytic bacteria, especially those belonging to Enterobacteriaceae. Two new semiselective media were developed. The selectivity of KC and NCTM3 media was achieved using cephalexin 40 mg l(-1), kasugamycin 20 mg l(-1) and neomycin 1 mg l(-1), cephalexin 100 mg l(-1), trimethoprime 5 mg l(-1), pivmecillinam 100 mg l(-1) respectively. Plating efficiencies ranged from 76 to 104% and from 78 to 132% for KC and NCTM3 respectively.
CONCLUSIONS
The new media allowed the growth of X. campestris pv. mangiferaeindicae whatever its country of isolation. The pathogen was repeatedly isolated with these media from asymptomatic leaves sampled in growth chamber experiments.
SIGNIFICANCE AND IMPACT OF THE STUDY
This work provides a description of new semiselective media, which should be valuable tools to study the ecology and epidemiology of X. campestris pv. mangiferaeindicae.
Topics: Amdinocillin Pivoxil; Aminoglycosides; Anti-Bacterial Agents; Anti-Infective Agents, Urinary; Cephalexin; Culture Media; Mangifera; Microbial Sensitivity Tests; Neomycin; Plant Diseases; Plant Leaves; Trimethoprim; Xanthomonas; Xanthomonas campestris
PubMed: 16162231
DOI: 10.1111/j.1365-2672.2005.02681.x