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Ceftizoxime, Cefdinir, Cefditoren, Cefpodoxime, Ceftibuten, Cefsulodin, and Cefpiramide
Published in M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson, Kucers’ The Use of Antibiotics, 2017
Mesut Yilmaz, David L. Paterson
Cefdinir, cefditoren, and ceftibuten are orally administered third-generation cephalosporins that find a place in treatment of respiratory tract infections, tonsillitis, and some skin infections. They have all been marketed in the United States.
Antimicrobial pharmacokinetics and preclinical in vitro models to support optimized treatment approaches for uncomplicated lower urinary tract infections
Published in Expert Review of Anti-infective Therapy, 2021
Iain J. Abbott, Jason A. Roberts, Joseph Meletiadis, Anton Y. Peleg
Novel antimicrobial agents hold some promise for the future, although clinical trials are needed. In 2020, the WHO published a target product profile to guide the urgent development of new oral antimicrobial agents for UTIs, which, in turn, would benefit from assessment within a dynamic bladder infection PK/PD in vitro model [316]. Novel oral β-lactamase inhibitor combinations can expand the antimicrobial activity against ESBL-producing uropathogens [209]. 3GC agents (cefpodoxime and ceftibuten) have been paired with β-lactamase inhibitors such as QPX7728, ETX0282 and VNRX7145, while ceftibuten has been paired with clavulanate [317–320]. In addition, an orally absorbed derivative of avibactam has been developed [321], and oral carbapenems, sulopenem and tebipenem, are under investigation [322,323].
Treatment of urinary tract infections in the era of antimicrobial resistance and new antimicrobial agents
Published in Postgraduate Medicine, 2020
Mazen S. Bader, Mark Loeb, Daniela Leto, Annie A. Brooks
Oral cephalosporins (cephalexin, cefpodoxime, ceftibuten, cefadroxil, cefixime) are the fourth most active antimicrobial agents, after nitrofurantoin, fosfomycin, and pivmecillinam, against E. coli (Table 1) [7,8,26–28]. However, cephalexin is among the broad-spectrum antibiotics that are associated with increased rates of drug-related adverse events and antibiotic-associated diarrhea [29]. For unclear reasons, elderly patients with UTIs who were prescribed cephalexin had greater risk of hospitalization due to sepsis and death [30]. The outcome was not adjusted for the severity of infection and patients who received cephalexin might have more severe infection than patients who received nitrofurantoin. However, oral cephalosporins can be used as empiric or definitive treatment of uncomplicated cystitis in case of resistance and allergy to first-line antibiotics (nitrofurantoin and fosfomycin), kidney dysfunction (creatinine clearance <30 mL/min), UTIs due to Enterobacteriales other than E coli (Klebsiella pneumoniae, proteus mirabilis) [8].
Pharmacokinetics-pharmacodynamics of β-lactamase inhibitors: are we missing the target?
Published in Expert Review of Anti-infective Therapy, 2019
Marguerite L Monogue, David P Nicolau
There are limited available data on the PK/PD of clavulanate. Early studies found that 0.12 µg/mL and 0.01–0.05 µg/mL of clavulanate were required to inhibit the β-lactamases of H. influenzae and M. catarrhalis, respectively [33]. More recent data examined the exposure-response relationship of clavulanate in combination with ceftibuten against ESBL producing E. coli and Klebsiella pneumoniae [34]. When combined with a fixed ceftibuten exposure of ~59% fT > MIC in an in vitro model, fT > threshold resulted in the best PK/PD index (R2 = 0.85) compared with fAUC/threshold and fCmax/threshold. For both E. coli and K. pneumoniae isolates, stasis and 1-log10 CFU reductions were achieved at 30.9–51.9 and 47.9–92.0% fT > ceftibuten concentration of the 2:1 ceftibuten/clavulanate MIC (threshold), respectively. In a murine thigh infection model, the fT > 0.5 µg/mL (clavulanate) was the PK/PD index that best correlated with the efficacy, with 20.6% fT > 0.5 µg/mL (clavulanate) associated with bacterial stasis [35]. Humanized exposures of ceftibuten-clavulanate (clavulanate fT > 0.5 value of 56.3%) achieved stasis in 20/22 Enterobacteriaceae expressing ß–lactamases (CTX-M, TEM and SHV wild-types and SHV-ESBL) with MICs ≤ 4 µg/mL [35].