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Filip Jansaker - One of the best experts on this subject based on the ideXlab platform.
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mutational change of ctx m 15 to ctx m 127 resulting in Mecillinam resistant escherichia coli during pivMecillinam treatment of a patient
MicrobiologyOpen, 2019Co-Authors: Karen Leth Nielsen, Frederik Boetius Hertz, Niels Frimodtmoller, Jenny Dahl Knudsen, Katrine Hartung Hansen, Jesper Bo Nielsen, Kristian Schonning, Filip JansakerAbstract: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 blaCTX-M-15 to blaCTX-M-127 , 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 blaCTX-M-15 with additional contribute from the serotype shift. We continue to recommend the use of pivMecillinam as first-line treatment for UTI.
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pivMecillinam for uncomplicated lower urinary tract infections caused by staphylococcus saprophyticus cumulative observational data from four recent clinical studies
Antibiotics, 2019Co-Authors: Filip Jansaker, Niels Frimodtmoller, Lars Bjerrum, Ingvild Vik, Marianne Bollestad, Morten Lindbaek, Jenny Dahl KnudsenAbstract:Objectives: To investigate pivMecillinam´s efficacy in uncomplicated lower urinary tract infection (UTI) caused by Staphylococcus saprophyticus—considered non-susceptible to Mecillinam. Methods: Participants with confirmed UTIs caused by S. saprophyticus from four randomized controlled trials, where pivMecillinam was empirically given to females with symptoms of UTIs. The primary outcome was defined as a cumulative clinical effect—symptom resolution during the first eight days of therapy, without a recurrence of UTI symptoms in the long-term follow-up (approximately four weeks). Secondary outcomes included the bacteriological effect—elimination of the causative agent, with or without new uropathogenic bacteria present in the first control urine sample. Significant bacteriuria was defined as ≥103 bacteria/mL. The antibiotic susceptibility testing was done by disc diffusion methodology, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Results: Seventy-four females (18–55 years) were empirically treated with pivMecillinam for UTIs caused by S. saphrophyticus (mean age 25 years; standard deviation (SD) 5.8). The cumulative clinical effect was 53/74 (72%), and the bacteriological effect was 51/59 (86%). Conclusion: PivMecillinam showed a high clinical and bacteriological effect in UTIs caused by S. saprophyticus in these four clinical trials. The characterization of non-susceptibility for Mecillinam regarding the treatment of UTIs caused by this common pathogen may need to be revised.
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in vivo Mecillinam resistance in escherichia coli after pivMecillinam treatment of a urinary tract infection
MicrobiologyOpen, 2019Co-Authors: Karen Leth Nielsen, Frederik Boetius Hertz, Niels Frimodtmoller, Jenny Dahl Knudsen, Katrine Hartung Hansen, Filip JansakerAbstract:PivMecillinam (amdinocillin pivoxil) is the recommended first choice antibiotic used to treat urinary tract infections (UTIs) in Denmark. Yet, in laboratory settings the frequency of mutation to Mecillinam resistance has been found to be very high. Treatment of UTI has a good clinical response, but low bacteriological cure rates. Prevalence of Mecillinam resistance in Escherichia coli remains low in spite of many years of use. We describe occurrence of in vivo Mecillinam resistance in a clinical isolate of extended-spectrum β-lactamase producing E. coli following pivMecillinam treatment. The only identified phenotypic differences in MEC-R compared to the original MEC-S isolate were full-length lipopolysaccharides with O-antigen (O25), Mecillinam resistance, and a lower minimum inhibitory concentration for ceftazidime. Whether the serotype change and mutation in fhlA is the cause of the Mecillinam resistance is unknown. Further studies are required to elucidate this possible mechanism. We continue to recommend the use of pivMecillinam as first-line treatment for UTI, yet Mecillinam treatment for other foci should be investigated.
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PivMecillinam for Uncomplicated Lower Urinary Tract Infections Caused by Staphylococcus saprophyticus—Cumulative Observational Data from Four Recent Clinical Studies
MDPI AG, 2019Co-Authors: Filip Jansaker, Lars Bjerrum, Ingvild Vik, Marianne Bollestad, Morten Lindbaek, Niels Frimodt-møller, Jenny Dahl KnudsenAbstract:Objectives: To investigate pivMecillinam´s efficacy in uncomplicated lower urinary tract infection (UTI) caused by Staphylococcus saprophyticus—considered non-susceptible to Mecillinam. Methods: Participants with confirmed UTIs caused by S. saprophyticus from four randomized controlled trials, where pivMecillinam was empirically given to females with symptoms of UTIs. The primary outcome was defined as a cumulative clinical effect—symptom resolution during the first eight days of therapy, without a recurrence of UTI symptoms in the long-term follow-up (approximately four weeks). Secondary outcomes included the bacteriological effect—elimination of the causative agent, with or without new uropathogenic bacteria present in the first control urine sample. Significant bacteriuria was defined as ≥103 bacteria/mL. The antibiotic susceptibility testing was done by disc diffusion methodology, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Results: Seventy-four females (18−55 years) were empirically treated with pivMecillinam for UTIs caused by S. saphrophyticus (mean age 25 years; standard deviation (SD) 5.8). The cumulative clinical effect was 53/74 (72%), and the bacteriological effect was 51/59 (86%). Conclusion: PivMecillinam showed a high clinical and bacteriological effect in UTIs caused by S. saprophyticus in these four clinical trials. The characterization of non-susceptibility for Mecillinam regarding the treatment of UTIs caused by this common pathogen may need to be revised
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pivMecillinam treatment of community acquired uncomplicated pyelonephritis based on sparse data
Global Journal of Infectious Diseases and Clinical Research, 2015Co-Authors: Filip Jansaker, Frederik Boetius Hertz, Niels Frimodtmoller, Jenny Dahl KnudsenAbstract:Background: PivMecillinam has good pharmacokinetic properties for treatment of infections in the urinary tract, and the Mecillinam resistance rate in Enterobacteriaceae is very low. In a European guideline pivMecillinam is recommended as a first-line drug for treatment of lower urinary tract infections. In Danish and Norwegian guidelines pivMecillinam is also recommended for acute uncomplicated pyelonephritis, although with very sparse documentation of effect.
Jenny Dahl Knudsen - One of the best experts on this subject based on the ideXlab platform.
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mutational change of ctx m 15 to ctx m 127 resulting in Mecillinam resistant escherichia coli during pivMecillinam treatment of a patient
MicrobiologyOpen, 2019Co-Authors: Karen Leth Nielsen, Frederik Boetius Hertz, Niels Frimodtmoller, Jenny Dahl Knudsen, Katrine Hartung Hansen, Jesper Bo Nielsen, Kristian Schonning, Filip JansakerAbstract: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 blaCTX-M-15 to blaCTX-M-127 , 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 blaCTX-M-15 with additional contribute from the serotype shift. We continue to recommend the use of pivMecillinam as first-line treatment for UTI.
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pivMecillinam for uncomplicated lower urinary tract infections caused by staphylococcus saprophyticus cumulative observational data from four recent clinical studies
Antibiotics, 2019Co-Authors: Filip Jansaker, Niels Frimodtmoller, Lars Bjerrum, Ingvild Vik, Marianne Bollestad, Morten Lindbaek, Jenny Dahl KnudsenAbstract:Objectives: To investigate pivMecillinam´s efficacy in uncomplicated lower urinary tract infection (UTI) caused by Staphylococcus saprophyticus—considered non-susceptible to Mecillinam. Methods: Participants with confirmed UTIs caused by S. saprophyticus from four randomized controlled trials, where pivMecillinam was empirically given to females with symptoms of UTIs. The primary outcome was defined as a cumulative clinical effect—symptom resolution during the first eight days of therapy, without a recurrence of UTI symptoms in the long-term follow-up (approximately four weeks). Secondary outcomes included the bacteriological effect—elimination of the causative agent, with or without new uropathogenic bacteria present in the first control urine sample. Significant bacteriuria was defined as ≥103 bacteria/mL. The antibiotic susceptibility testing was done by disc diffusion methodology, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Results: Seventy-four females (18–55 years) were empirically treated with pivMecillinam for UTIs caused by S. saphrophyticus (mean age 25 years; standard deviation (SD) 5.8). The cumulative clinical effect was 53/74 (72%), and the bacteriological effect was 51/59 (86%). Conclusion: PivMecillinam showed a high clinical and bacteriological effect in UTIs caused by S. saprophyticus in these four clinical trials. The characterization of non-susceptibility for Mecillinam regarding the treatment of UTIs caused by this common pathogen may need to be revised.
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in vivo Mecillinam resistance in escherichia coli after pivMecillinam treatment of a urinary tract infection
MicrobiologyOpen, 2019Co-Authors: Karen Leth Nielsen, Frederik Boetius Hertz, Niels Frimodtmoller, Jenny Dahl Knudsen, Katrine Hartung Hansen, Filip JansakerAbstract:PivMecillinam (amdinocillin pivoxil) is the recommended first choice antibiotic used to treat urinary tract infections (UTIs) in Denmark. Yet, in laboratory settings the frequency of mutation to Mecillinam resistance has been found to be very high. Treatment of UTI has a good clinical response, but low bacteriological cure rates. Prevalence of Mecillinam resistance in Escherichia coli remains low in spite of many years of use. We describe occurrence of in vivo Mecillinam resistance in a clinical isolate of extended-spectrum β-lactamase producing E. coli following pivMecillinam treatment. The only identified phenotypic differences in MEC-R compared to the original MEC-S isolate were full-length lipopolysaccharides with O-antigen (O25), Mecillinam resistance, and a lower minimum inhibitory concentration for ceftazidime. Whether the serotype change and mutation in fhlA is the cause of the Mecillinam resistance is unknown. Further studies are required to elucidate this possible mechanism. We continue to recommend the use of pivMecillinam as first-line treatment for UTI, yet Mecillinam treatment for other foci should be investigated.
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PivMecillinam for Uncomplicated Lower Urinary Tract Infections Caused by Staphylococcus saprophyticus—Cumulative Observational Data from Four Recent Clinical Studies
MDPI AG, 2019Co-Authors: Filip Jansaker, Lars Bjerrum, Ingvild Vik, Marianne Bollestad, Morten Lindbaek, Niels Frimodt-møller, Jenny Dahl KnudsenAbstract:Objectives: To investigate pivMecillinam´s efficacy in uncomplicated lower urinary tract infection (UTI) caused by Staphylococcus saprophyticus—considered non-susceptible to Mecillinam. Methods: Participants with confirmed UTIs caused by S. saprophyticus from four randomized controlled trials, where pivMecillinam was empirically given to females with symptoms of UTIs. The primary outcome was defined as a cumulative clinical effect—symptom resolution during the first eight days of therapy, without a recurrence of UTI symptoms in the long-term follow-up (approximately four weeks). Secondary outcomes included the bacteriological effect—elimination of the causative agent, with or without new uropathogenic bacteria present in the first control urine sample. Significant bacteriuria was defined as ≥103 bacteria/mL. The antibiotic susceptibility testing was done by disc diffusion methodology, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Results: Seventy-four females (18−55 years) were empirically treated with pivMecillinam for UTIs caused by S. saphrophyticus (mean age 25 years; standard deviation (SD) 5.8). The cumulative clinical effect was 53/74 (72%), and the bacteriological effect was 51/59 (86%). Conclusion: PivMecillinam showed a high clinical and bacteriological effect in UTIs caused by S. saprophyticus in these four clinical trials. The characterization of non-susceptibility for Mecillinam regarding the treatment of UTIs caused by this common pathogen may need to be revised
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pivMecillinam treatment of community acquired uncomplicated pyelonephritis based on sparse data
Global Journal of Infectious Diseases and Clinical Research, 2015Co-Authors: Filip Jansaker, Frederik Boetius Hertz, Niels Frimodtmoller, Jenny Dahl KnudsenAbstract:Background: PivMecillinam has good pharmacokinetic properties for treatment of infections in the urinary tract, and the Mecillinam resistance rate in Enterobacteriaceae is very low. In a European guideline pivMecillinam is recommended as a first-line drug for treatment of lower urinary tract infections. In Danish and Norwegian guidelines pivMecillinam is also recommended for acute uncomplicated pyelonephritis, although with very sparse documentation of effect.
Gunnar Kahlmeter - One of the best experts on this subject based on the ideXlab platform.
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high genetic diversity of nitrofurantoin or Mecillinam resistant escherichia coli indicates low propensity for clonal spread
Journal of Antimicrobial Chemotherapy, 2013Co-Authors: Hanna Oden Poulsen, Gunnar Kahlmeter, Anders Johansson, Susanne Granholm, Martin SundqvistAbstract:The empirical treatment with trimethoprim or ciprofloxacin of urinary tract infections (UTIs) is now questioned, partly due to the global expansion of a few resistant clonal groups of Escherichia c ...
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antimicrobial susceptibility of escherichia coli from community acquired urinary tract infections in europe the eco sens study revisited
International Journal of Antimicrobial Agents, 2012Co-Authors: Gunnar Kahlmeter, Hanna Oden PoulsenAbstract:Abstract This study determined the antimicrobial susceptibility of Escherichia coli causing community-acquired, acute, uncomplicated, non-recurrent urinary tract infection in unselected women aged 18–65 years and compared the results with those obtained 8 years earlier in the first ECO·SENS study (1999–2000). During 2007–2008, urine samples were taken from 1697 women in Austria, Greece, Portugal, Sweden and the UK. The countries were chosen to represent areas of Europe indicated to have more (Greece and Portugal) or less (UK, Austria and Sweden) problems with resistance. Antimicrobial susceptibility testing of 903 E. coli isolates (150–200 isolates per country) to 14 antimicrobials was performed by disk diffusion using European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. In E. coli , resistance to Mecillinam, cefadroxil (representing oral cephalosporins), nitrofurantoin, fosfomycin trometamol, gentamicin and the third-generation cephalosporins cefotaxime and ceftazidime was
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non hospital antimicrobial usage and resistance in community acquired escherichia coli urinary tract infection
Journal of Antimicrobial Chemotherapy, 2003Co-Authors: Gunnar Kahlmeter, P Menday, O CarsAbstract:Objectives To investigate the correlation between non-hospital antimicrobial consumption and resistance. Methods Information on the non-hospital sales of antimicrobials from 14 European countries in 1997 and 2000 was compared with the antimicrobial resistance profiles of Escherichia coli isolated from women with community-acquired urinary tract infection in the same countries in 1999/2000. Results There was no statistically significant correlation between the consumption of and resistance to co-amoxiclav, cefadroxil, fosfomycin, Mecillinam, sulfamethoxazole, trimethoprim or trimethoprim-sulfamethoxazole. On the other hand, there were statistically significant correlations between consumption of broad-spectrum penicillins and quinolones in 1997 and 2000 and resistance to ciprofloxacin (P range 0.0005-0.0045) and nalidixic acid (P range 0.0013-0.0049). Total antimicrobial consumption in 1997 was significantly correlated to ciprofloxacin (P=0.0009) and nalidixic acid (P=0.0018) resistance, and there were significant relationships between quinolone consumption in both years and resistance to gentamicin (P range 0.0029-0.0043) and nitrofurantoin (P range 0.0003-0.0007). E. coli with multiple antimicrobial resistance were significantly more common in countries with high total antimicrobial consumption. Conclusions Owing to the frequent presence of many possible confounding factors, antimicrobial resistance to one drug does not always correlate well to the consumption of the same drug or closely related drugs. This study showed that the degree of antimicrobial consumption was significantly correlated to the incidence of multidrug-resistant E. coli.
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the eco sens project a prospective multinational multicentre epidemiological survey of the prevalence and antimicrobial susceptibility of urinary tract pathogens interim report
Journal of Antimicrobial Chemotherapy, 2000Co-Authors: Gunnar KahlmeterAbstract:The ECO.SENS Project is the first international survey to investigate the prevalence and susceptibility of pathogens causing community-acquired, uncomplicated urinary tract infections (UTIs) in women. At 240 centres in 17 countries, female patients presenting with symptoms of uncomplicated UTIs were asked to provide a urine sample for testing for the presence of leucocytes and bacteria. The bacteria were identified and their susceptibility to 12 antibiotics commonly used in the treatment of UTIs was determined. The objective of the survey was to collect 5000 urine samples to obtain approximately 3500 isolates of defined uropathogens. This interim report includes the results from 1960 urine samples, 75% of which contained a uropathogen. Escherichia coli accounted for the majority (80%) of uropathogens isolated in all 17 countries. The rates of resistance among E. coli strains were: ampicillin and sulphamethoxazole, 30%; trimethoprim alone or with sulphamethoxazole, 15%; nalidixic acid, 6%; ciprofloxacin, 3%; amoxycillin-clavulanic acid, Mecillinam, cefadroxil, nitrofurantoin and fosfomycin, < or =2%. The use of ampicillin, sulphonamides and trimethoprim alone or with sulphamethoxazole needs to be reconsidered. The seemingly rapid increase in quinolone resistance among community-acquired E. coli in some of the countries gives cause for concern.
Alexander Mischnik - One of the best experts on this subject based on the ideXlab platform.
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Susceptibility to penicillin derivatives among third-generation cephalosporin-resistant Enterobacteriaceae recovered on hospital admission.
Diagnostic microbiology and infectious disease, 2016Co-Authors: Alexander Mischnik, Philipp Baumert, Axel Hamprecht, Anna M. Rohde, Silke Peter, Susanne Feihl, Johannes K.-m. Knobloch, Hanna Gölz, Axel Kola, Birgit ObermannAbstract:As part of the multicenter Antibiotic Therapy Optimisation Study-the largest study on the prevalence of third-generation cephalosporin-resistant Enterobacteriaceae carriage upon hospital admission-minimum inhibitory concentration values were generated for ampicillin/sulbactam, amoxicillin/clavulanic acid, piperacillin/tazobactam, Mecillinam, Mecillinam/clavulanic acid, and temocillin against third-generation cephalosporin-resistant Escherichia coli, Klebsiella species and Enterobacter species.
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activity of temocillin Mecillinam ceftazidime and ceftazidime avibactam against carbapenem non susceptible enterobacteriaceae without carbapenemase production
European Journal of Clinical Microbiology & Infectious Diseases, 2015Co-Authors: Nico T Mutters, Alexander Mischnik, Stefan Zimmermann, Martin KaaseAbstract:Treatment options for multidrug-resistant Gram-negative infections are scarce and therefore alternatives with a narrow spectrum or new agents are sought. Antimicrobial susceptibility to temocillin, Mecillinam, ceftazidime, and ceftazidime/avibactam was determined using Etest and disk diffusion according to European Committee on Antimicrobial Susceptibility Testing (EUCAST) methodology. A total of 77 carbapenem-nonsusceptible Enterobacteriaceae were studied, including Klebsiella pneumoniae (26%), Escherichia coli (26%), Enterobacter cloacae (26%), and Enterobacter aerogenes (22%). Several phenotypic tests, PCRs followed by sequencing and a microbiological bioassay excluded carbapenemase production in all isolates. Antimicrobial susceptibility rates were low for temocillin (15.6%, minimum inhibitory concentration [MIC] range 2 to >1,024 μg/ml), moderate for Mecillinam (59.7%, MIC range 0.25 to >256 μg/ml), and excellent for ceftazidime/avibactam (100%, zone diameter range 19 to 32 mm, median 25 mm). 5.2% of the isolates were susceptible to ceftazidime alone (zone diameter range 6 to 32 mm). In this study, Mecillinam exhibited moderate and ceftazidime/avibactam excellent in vitro antimicrobial activity against carbapenem-nonsusceptible Enterobacteriaceae without carbapenemase production. Ceftazidime/avibactam was able to restore previously reduced susceptibility to ceftazidime in all isolates, thus potentiating its activity. Temocillin only exhibited low in vitro antimicrobial activity against the isolates. Further evaluation of Mecillinam and ceftazidime/avibactam with regard to the potential clinical utility against infections caused by these pathogens has to be performed.
Niels Frimodtmoller - One of the best experts on this subject based on the ideXlab platform.
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mutational change of ctx m 15 to ctx m 127 resulting in Mecillinam resistant escherichia coli during pivMecillinam treatment of a patient
MicrobiologyOpen, 2019Co-Authors: Karen Leth Nielsen, Frederik Boetius Hertz, Niels Frimodtmoller, Jenny Dahl Knudsen, Katrine Hartung Hansen, Jesper Bo Nielsen, Kristian Schonning, Filip JansakerAbstract: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 blaCTX-M-15 to blaCTX-M-127 , 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 blaCTX-M-15 with additional contribute from the serotype shift. We continue to recommend the use of pivMecillinam as first-line treatment for UTI.
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pivMecillinam for uncomplicated lower urinary tract infections caused by staphylococcus saprophyticus cumulative observational data from four recent clinical studies
Antibiotics, 2019Co-Authors: Filip Jansaker, Niels Frimodtmoller, Lars Bjerrum, Ingvild Vik, Marianne Bollestad, Morten Lindbaek, Jenny Dahl KnudsenAbstract:Objectives: To investigate pivMecillinam´s efficacy in uncomplicated lower urinary tract infection (UTI) caused by Staphylococcus saprophyticus—considered non-susceptible to Mecillinam. Methods: Participants with confirmed UTIs caused by S. saprophyticus from four randomized controlled trials, where pivMecillinam was empirically given to females with symptoms of UTIs. The primary outcome was defined as a cumulative clinical effect—symptom resolution during the first eight days of therapy, without a recurrence of UTI symptoms in the long-term follow-up (approximately four weeks). Secondary outcomes included the bacteriological effect—elimination of the causative agent, with or without new uropathogenic bacteria present in the first control urine sample. Significant bacteriuria was defined as ≥103 bacteria/mL. The antibiotic susceptibility testing was done by disc diffusion methodology, according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Results: Seventy-four females (18–55 years) were empirically treated with pivMecillinam for UTIs caused by S. saphrophyticus (mean age 25 years; standard deviation (SD) 5.8). The cumulative clinical effect was 53/74 (72%), and the bacteriological effect was 51/59 (86%). Conclusion: PivMecillinam showed a high clinical and bacteriological effect in UTIs caused by S. saprophyticus in these four clinical trials. The characterization of non-susceptibility for Mecillinam regarding the treatment of UTIs caused by this common pathogen may need to be revised.
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in vivo Mecillinam resistance in escherichia coli after pivMecillinam treatment of a urinary tract infection
MicrobiologyOpen, 2019Co-Authors: Karen Leth Nielsen, Frederik Boetius Hertz, Niels Frimodtmoller, Jenny Dahl Knudsen, Katrine Hartung Hansen, Filip JansakerAbstract:PivMecillinam (amdinocillin pivoxil) is the recommended first choice antibiotic used to treat urinary tract infections (UTIs) in Denmark. Yet, in laboratory settings the frequency of mutation to Mecillinam resistance has been found to be very high. Treatment of UTI has a good clinical response, but low bacteriological cure rates. Prevalence of Mecillinam resistance in Escherichia coli remains low in spite of many years of use. We describe occurrence of in vivo Mecillinam resistance in a clinical isolate of extended-spectrum β-lactamase producing E. coli following pivMecillinam treatment. The only identified phenotypic differences in MEC-R compared to the original MEC-S isolate were full-length lipopolysaccharides with O-antigen (O25), Mecillinam resistance, and a lower minimum inhibitory concentration for ceftazidime. Whether the serotype change and mutation in fhlA is the cause of the Mecillinam resistance is unknown. Further studies are required to elucidate this possible mechanism. We continue to recommend the use of pivMecillinam as first-line treatment for UTI, yet Mecillinam treatment for other foci should be investigated.
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pivMecillinam treatment of community acquired uncomplicated pyelonephritis based on sparse data
Global Journal of Infectious Diseases and Clinical Research, 2015Co-Authors: Filip Jansaker, Frederik Boetius Hertz, Niels Frimodtmoller, Jenny Dahl KnudsenAbstract:Background: PivMecillinam has good pharmacokinetic properties for treatment of infections in the urinary tract, and the Mecillinam resistance rate in Enterobacteriaceae is very low. In a European guideline pivMecillinam is recommended as a first-line drug for treatment of lower urinary tract infections. In Danish and Norwegian guidelines pivMecillinam is also recommended for acute uncomplicated pyelonephritis, although with very sparse documentation of effect.
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clinical and bacteriological effects of pivMecillinam for esbl producing escherichia coli or klebsiella pneumoniae in urinary tract infections
Journal of Antimicrobial Chemotherapy, 2014Co-Authors: Filip Jansaker, Niels Frimodtmoller, Ingegerd Sjogren, Jenny Dahl KnudsenAbstract:Objectives 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. Here, we evaluated the clinical and bacteriological effects of pivMecillinam in UTIs caused by ESBL-producing Enterobacteriaceae. Methods We carried out a prospective follow-up of 39 patients diagnosed with UTI caused by ESBL-producing Enterobacteriaceae, initiated on pivMecillinam. The patients were from general practice (n = 29) or admitted to hospitals (n = 10) in the Copenhagen area, Denmark (n = 30) or Halland, Sweden (n = 9). Both patients and physicians were asked to complete a questionnaire on the pretreatment signs and symptoms. Patients were asked to send in two more urine samples for culture examination, together with questionnaires for clinical effect, 2-6 and 10-20 days, respectively, after end of treatment. Results Of the 39 patients included, 30 received a treatment regimen of 400 mg of pivMecillinam three times a day and 9 received 200 mg three times a day. All isolates were susceptible to Mecillinam. The bacteriological cure rate was 79% (31/39); 80% (24/30) and 78% (7/9) for 400 and 200 mg three times a day, respectively. Relapse, i.e. ESBL-producing bacteria in the second control urine after previous bacteriological cure, was seen in five patients. Clinical cure was evaluable in 19 patients; 16 had a clinical effect (84%). Conclusions PivMecillinam was proven bacteriologically and clinically effective for treatment of lower UTIs caused by ESBL-producing Enterobacteriaceae.