Thrice-weekly temocillin administered after each dialysis session is appropriate for the treatment of serious Gram-negative infections in haemodialysis patients

Vandecasteele, Stefaan; Bastos, Ana C. Miranda; Capron, Arnaud; Spinewine, Anne; Tulkens, Paul M.; Bambeke, Françoise Van

doi:10.1016/j.ijantimicag.2015.09.005

Cited by 5 publications

(2 citation statements)

References 27 publications

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“…Temocillin is highly dialysable, with a fraction eliminated by dialysis of approximately 55% [13]. Vandecasteele et al proposed a three-times-weekly schedule (2 g every 48 h), during which the free serum concentration remained above the MIC as high as 50-90%, even for MICs of 16 mg/L [13,16]. Temocillin was found stable at 37 • C for 24 h, suggesting that prolonged or continued infusion dosing could be suitable, particularly for critically ill patients [17].…”

Section: Introductionmentioning

confidence: 99%

Temocillin: Applications in Antimicrobial Stewardship as a Potential Carbapenem-Sparing Antibiotic

et al. 2022

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Temocillin is an old antibiotic, but given its particular characteristics, it may be a suitable alternative to carbapenems for treating infections due to ESBL-producing Enterobacterales and uncomplicated UTI due to KPC-producers. In this narrative review, the main research question was to summarize current evidence on temocillin and its uses in infectious diseases. A search was run on PubMed using the terms (‘Temocillin’ [Mesh]) AND (‘Infection’ [Mesh]). Current knowledge regarding temocillin in urinary tract infection, blood-stream infections, pneumonia, intra-abdominal infections, central nervous system infections, skin and soft tissues infections, surgical sites infections and osteoarticular Infections were summarized. Temocillin retain a favourable profile on microbiota and risk of Clostridioides difficile infections and could be an option for treating outpatients. Temocillin may be a valuable tool to treat susceptible pathogens and for which a carbapenem could be spared. Other advantages in temocillin use are that it is well-tolerated; it is associated with a low rate of C. difficile infections; it is active against ESBL, AmpC, and KPC-producing Enterobacterales; and it can be used in the OPAT clinical setting.

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Section: Introductionmentioning

confidence: 99%

Temocillin: Applications in Antimicrobial Stewardship as a Potential Carbapenem-Sparing Antibiotic

et al. 2022

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“…even KPCs (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18). In addition, temocillin demonstrated efficacy in in vivo infection models as well as in patients (19)(20)(21).…”

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confidence: 99%

Resurrecting Old β-Lactams: Potent Inhibitory Activity of Temocillin against Multidrug-ResistantBurkholderiaSpecies Isolates from the United States

Zeiser

Becka

Barnes

et al. 2019

Antimicrob Agents Chemother

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Burkholderia spp. are opportunistic human pathogens that infect persons with cystic fibrosis and the immunocompromised. Burkholderia spp. express class A and C ␤-lactamases, which are transcriptionally regulated by PenR A through linkage to cell wall metabolism and ␤-lactam exposure. The potency of temocillin, a 6-methoxy-␤-lactam, was tested against a panel of multidrug-resistant (MDR) Burkholderia spp. In addition, the mechanistic basis of temocillin activity was assessed and compared to that of ticarcillin. Susceptibility testing with temocillin and ticarcillin was conducted, as was biochemical analysis of the PenA1 class A ␤-lactamase and AmpC1 class C ␤-lactamase. Molecular dynamics simulations (MDS) were performed using PenA1 with temocillin and ticarcillin. The majority (86.7%) of 150 MDR Burkholderia strains were susceptible to temocillin, while only 4% of the strains were susceptible to ticarcillin. Neither temocillin nor ticarcillin induced bla expression. Ticarcillin was hydrolyzed by PenA1 (k cat /K m ϭ 1.7 Ϯ 0.2 M Ϫ1 s Ϫ1 ), while temocillin was slow to form a favorable complex (apparent K i [K i app ] ϭ ϳ2 mM). Ticarcillin and temocillin were both potent inhibitors of AmpC1, with K i app values of 4.9 Ϯ 1.0 M and 4.3 Ϯ 0.4 M, respectively. MDS of PenA revealed that ticarcillin is in an advantageous position for acylation and deacylation. Conversely, with temocillin, activesite residues K73 and S130 are rotated and the catalytic water molecule is displaced, thereby slowing acylation and allowing the 6-methoxy of temocillin to block deacylation. Temocillin is a ␤-lactam with potent activity against Burkholderia spp., as it does not induce bla expression and is poorly hydrolyzed by endogenous ␤-lactamases.

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Pharmacokinetics and Pharmacodynamics of Temocillin

Alexandre

Fantin

2017

Clin Pharmacokinet

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Temocillin, a 6-α-methoxy derivative of ticarcillin, is a forgotten antibiotic that has recently been rediscovered, and issues about clinical breakpoints and optimal therapeutic regimens are still ongoing. Temocillin spectrum is almost restricted to Enterobacteriaceae. The addition of the α-methoxy moiety on ticarcillin confers resistance to hydrolysis by Ambler classes A and C β-lactamases (extended spectrum β-lactamases, Klebsiella pneumoniae carbapenemase and AmpC hyperproduced enzymes). Temocillin is bactericidal, and the effect of inoculum size on its activity is relatively mild. The proportion of spontaneous resistant mutants in vitro to temocillin is low, as found in vivo. After intravenous infusion, temocillin showed a prolonged elimination half-life of approximately 5 h. The percentage of protein binding of temocillin is high (approximately 80%), and is concentration-dependent. Temocillin clearance is mainly renal, and urinary recovery is high, ranging from 72 to 82% after 24 h. Furthermore, the penetration of temocillin into bile and peritoneal fluid is high, but poor into cerebrospinal fluid. The cumulative percentage of a 24-h period during which the free drug concentration exceeds the minimum inhibitory concentration (fT > MIC) at steady-state pharmacokinetic conditions seems to be the best pharmacokinetic/pharmacodynamic (PK/PD) index correlating with temocillin efficacy. An fT > MIC of 40-50% is associated with antibacterial effect and survival in vivo. Monte Carlo simulations performed in critically ill patients showed that the 2 g every 12 h and 2 g every 8 h regimens provide a 95% probability of target attainment of 40% fT > MIC up to an MIC of 8 mg/L. In less severely ill patients or in specific foci of infection, such as urinary tract infection, a 4 g daily regimen should be adequate for strains with temocillin MIC up to 16 mg/L. Data regarding actual wild-type MIC distribution, clinical efficacy, PK profiling in volunteers or patients, and PD targets are scarce, and further studies are required to support appropriate dosing recommendations and determination of clinical breakpoints.

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Thrice-weekly temocillin administered after each dialysis session is appropriate for the treatment of serious Gram-negative infections in haemodialysis patients

Cited by 5 publications

References 27 publications

Temocillin: Applications in Antimicrobial Stewardship as a Potential Carbapenem-Sparing Antibiotic

Temocillin: Applications in Antimicrobial Stewardship as a Potential Carbapenem-Sparing Antibiotic

Resurrecting Old β-Lactams: Potent Inhibitory Activity of Temocillin against Multidrug-ResistantBurkholderiaSpecies Isolates from the United States

Pharmacokinetics and Pharmacodynamics of Temocillin

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