In vitro susceptibility to mecillinam of Escherichia coli strains isolated from the urine of pregnant women.

OBJECTIVES: Pivmecillinam is a safe beta-lactam for use in pregnancy. It has been widely used for the treatment of lower urinary tract infections (UTIs) in the Nordic countries where its efficacy, minor impact on the microbiota, and low level of resistance among the Escherichia coli strains have been proven. However, susceptibility data related to E. coli involved in asymptomatic bacteriuria and lower UTIs in pregnant women is lacking. We aimed to support the 2015 recommendations issued by the French Infectious Diseases Society (SPILF) on gestational UTI, with a particular focus on pivmecillinam. MATERIAL AND METHODS: Antimicrobial susceptibility testing was performed by 12 hospitals with a maternity department on 235 E. coli strains isolated from the urine of pregnant women. Susceptibility to mecillinam was tested by disk diffusion method using the 2015 recommendations of the antibiogram committee of the French microbiology society (CA-SFM). RESULTS: Global susceptibility to mecillinam was 86.4%. Susceptibility to mecillinam was 96.5% for strains susceptible to amoxicillin-clavulanic acid and 38.7% for resistant strains. All six extended-spectrum beta-lactamase-producing E. coli strains were susceptible to mecillinam. CONCLUSION: Given the efficacy and safety of pivmecillinam during pregnancy, it may be used for the documented treatment of asymptomatic bacteriuria and acute cystitis in pregnant women. It also represents an alternative for the treatment of multidrug-resistant bacterial infections.

Urine bactericidal activity against Escherichia coli isolates exhibiting different resistance phenotypes/genotypes in an in vitro pharmacodynamic model simulating urine concentrations obtained after oral administration of a 400-milligram single dose of cefditoren-pivoxil.

Activity of simulated cefditoren urinary concentrations was determined against seven Escherichia coli isolates. Bactericidal activity was obtained from 4 to 24 h against TEM-1 (penicillinase production/hyperproduction), TEM-34 (IRT-6), and TEM-116 (extended-spectrum beta-lactamase [ESBL]) and from 6 to 8 h against SHV/TEM-116 (ESBL) but never against SHV/TEM-1 (ESBL). Extension of bactericidal activity depended on the resistance genotype/phenotype tested.

Randomised trial of pivampicillin plus pivmecillinam vs. pivampicillin in children and young adults with chronic obstructive pulmonary disease and infection with Haemophilus influenzae.

A prospective, randomised, single-blind comparative trial was carried out to determine whether double beta-lactam treatment with pivampicillin plus pivmecillinam is more effective than pivampicillin alone in the treatment of recurrent and chronic lung infections with Haemophilus influenzae in patients with chronic obstructive pulmonary disease (COPD) or cystic fibrosis (CF). Fifty-six children and young adults with COPD or CF were randomised to the clinical study. The patients were allocated at random to receive perorally either pivmecillinam, 40 mg/kg/day, combined with pivampicillin, 50 mg/kg/day, or pivampicillin 50 mg/kg/day alone for 14 days. A cross-over pharmacokinetic study using the same drugs was carried out in 10 CF patients to determine the antibiotic concentrations in serum and sputum after a single dose of each drug. The clinical study showed no significant differences in clinical scoring, lung function tests or adverse events after treatment with pivampicillin plus pivmecillinam or pivampicillin alone. Follow-up microbiological evaluation 2 and 6 weeks after the end of treatment showed that the offending pathogen was eradicated in 68% of the patients treated with pivampicillin plus pivmecillinam and in 67% of the patients treated with pivampicillin alone. Reinfection with another biotype was more common in the combination group (50% vs. 21%) than in the pivampicillin group. In the pharmacokinetic study the median peak serum concentration occurred two hours after intake of tablets. The efficacy of double beta lactam treatment in lung infections with H. influenzae appears to be equivalent to that of ampicillin on clinical lung symptoms, lung function tests, adverse effects and bacteriology.

The pharmacokinetics of mecillinam and pivmecillinam in pregnant and non-pregnant women.

1. The pharmacokinetics of parenteral mecillinam (n = 27) and oral pivmecillinam (n = 12) were studied in pregnant (n = 27) and non-pregnant (n = 12) subjects. 2. In early pregnancy (9-14 weeks of gestation) the mean peak plasma drug concentration (Cmax = 19 +/- 9 micrograms ml-1) after an intravenous injection of 200 mg mecillinam was significantly lower (P less than 0.05) and the volume of distribution (V = 49 +/- 20.1) significantly larger (P less than 0.05) than in non-pregnant subjects (Cmax = 35 +/- 18 micrograms ml-1, V = 29 +/- 12.1). In late pregnancy (39-40 weeks of gestation) the plasma mean peak concentration (Cmax = (29 +/- 14 micrograms ml-1) after parenteral administration of 200 mg mecillinam was slightly lower and the volume of distribution (V = 65 +/- 29.1, V = 0.9 +/- 0.4 l kg-1) significantly larger than that in non-pregnant subjects (V = 0.4 +/- 0.3 l kg-1). Also after oral administration of 200 mg pivmecillinam, equimolar to 136.5 mg mecillinam, the mean peak plasma concentration in pregnant subjects (Cmax = 1.8 +/- 1.2 micrograms ml-1) was slightly lower than that in non-pregnant subjects (Cmax = 1.7 +/- 1.2 micrograms ml-1). 3. The mean half-life of elimination after parenteral administration of mecillinam was significantly longer during both early (t1/2,Z = 133 +/- 38 min, P less than 0.05) and late pregnancy (t1/2,Z = 107 +/- 41 min, P less than 0.05) as compared with the non-pregnant state (t1/2,Z = 75 +/- 21 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of food on bioavailability of amdinocillin pivoxil.

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.

Factors influencing the absorption and disposition of mecillinam and pivmecillinam in man.

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.