1. Validation of a HPLC-MS/MS assay for the determination of total and unbound concentration of temocillin in human serum
Perrin Ngougni Pokem, Ana C. Miranda Bastos, PaulM.Tulkens, PierreWallemacq, Françoise Van Bambeke, Arnaud Capron. Clinical Biochemistry 48 (2015) 542–545
Temocillin is a β-lactam antibiotic active against gram-negative bacteria, including β-lactamase producers. It is currently indicated for the treatment of septicemia, urinary tract infections, and lower respiratory tract infections. In the recent years the interest on this drug has been greatly enhanced, due to the increased incidence of infections caused by microorganisms producing extended-spectrum β-lactamases. This makes temocillin a strategic and interesting alternativeto carbapenems, especially with the current driving force to spare the use of these drugs.
Pharmacodynamic studies predict that therapeutic success with β-lactams depends on the time during which their unbound concentration in serum remains above the MIC of the offending organism. Dosage should thus be adapted to take into account not only the bacterial susceptibility, but also the rate of elimination of the drug. There is evidence of a wide interindividual variability in the temocillin serum levels so that standard dosing regimens may not be adequate in special patient populations such as intensive-care and end-stage renal disease patients. These patients may beneﬁt from individualized dose regimens based on therapeutic drug monitoring.
2. Evaluation of avibactam-supplemented combination disk tests for the detection of OXA-48 carbapenemase-producing Enterobacteriaceae
Te-Din Huang*, Catherine Berhin, Pierre Bogaerts, Youri Glupczynski. Diagnostic Microbiology and Infectious Disease 79 (2014) 252–254
The distribution of ertapenem, meropenem, and temocillin paper disks zone diameter and the different CDT diameter increase on all isolates tested are shown in this paper. 111/113 CPE and 57/100 non-carbapenemase producers isolates would have been categorized as carbapenem non-susceptible Enterobacteriaceae (CNSE) according to the EUCAST interpretative criteria. Among the 113 CPE isolates, 111 and 83, respectively, would have been detected by the ertapenem or meropenem screening breakpoint (<25mm) proposed by EUCAST. All but 1 (VIM-producing Enterobacter cloacae)of the CPE isolates missed by the EUCAST screening breakpoint were OXA-48 producers. Concerning temocillin, 36 of 100 non–carbapenemase- producing isolates were resistant according to the breakpoint (inhibition zone b20 mm) recently published, while all but 2 (1 NDM-positive M. morganii and 1 KPC-producing Klebsiella pneumoniae) of the 113 CPE strains were temocillin-resistant including 95% of the VIM (19/20) and of OXA-48 (68/72) producers having temocillin zone diameter b12mmand conﬁrming high-
level resistance to temocillin stated previously.
3. High-performance Liquid Chromatographic Assay of Temocillin and Epimerisation of its Diastereoisomers
Albert E. Bird, Chieh-Hua Charsley, Keith R. Jennings, Anthony C. Marshall. ANALYST,SEPTEMBER 1984,VOL.109
Substances related to temocillin and products formed by degradation of it in acid and alkali were chromatographed to investigate the specificity of the method. The related substances examined and their retention times are given in this paper. Degradation studies were carried out on solutions containing about 5 mg ml-1 of temocillin in 0.1 M sodium hydroxide solution and 0.1M hydrochloric acid at about 22 oC. After various times aliquots of the solutions were neutralised, diluted 1 + 9 with 0.1 M phosphate buffer (pH 7.0) and injected. In alkali, degradation was complete within 1 h, as shown by the absence of peaks at the temocillin retention times. The degradation products eluted within 5 min. After degradation for 24 h in acid, very small peaks were still present at the temocillin retention times and numerous degradation product peaks were present, eluting both before and after temocillin and well resolved from it. These results, together with those in this paper, show that the method has high specificity for temocillin.