The Journal of antimicrobial chemotherapy · 2026
Temocillin: a therapeutic alternative in bone and joint infections due to third generation cephalosporin-resistant Enterobacterales?
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Piquart Louise, Goutelle Sylvain, Maillard Mathieu, Boisset Sandrine, Carricajo Anne, Tristan Anne, Ranc Anne-Gaëlle, Laurent Frédéric, Dupieux Céline
Аннотация
BACKGROUND AND OBJECTIVES: Bone and joint infections (BJIs) due to third-generation cephalosporin-resistant (3GC-R) Enterobacterales are particularly challenging-to-treat infections, and their treatment often relies on carbapenems. Due to its stability towards various beta-lactamases, as well as its limited spectrum of activity, temocillin could be a promising alternative. This study evaluated the in vitro activity of temocillin against a collection of 3GC-R Enterobacterales isolates from BJIs and modelled the probability of PK/PD target attainment according to the dosage regimen used.
METHODS: MICs of temocillin and seven comparators (ertapenem, imipenem, meropenem, levofloxacin, delafloxacin, doxycycline and tigecycline) were determined using gradient strips for 104 3GC-R Enterobacterales isolates from BJIs in three French hospitals. Isolates were characterized about their mechanism of resistance to 3GC (ESBL or hyperproduced cephalosporinase). PK/PD simulations were performed with six dosage regimens and different stages of renal function in order to calculate PTA according to temocillin MIC.
RESULTS: Temocillin showed a susceptibility rate of 92.3% (96/104) in 3GC-R isolates from BJIs: 95.3% (61/64) in ESBL producers and 87.5% (35/40) in AmpC hyperproducers. Temocillin was the only alternative to carbapenems for 25% (26/104) of isolates. PTA values increased with declining renal function. In normorenal patients, none of the tested regimen achieved adequate PTA up to the Enterobacterales breakpoint (16 mg/L).
CONCLUSIONS: This study demonstrated the high in vitro efficacy of temocillin against 3GC-R Enterobacterales from BJIs, regardless of the underlying resistance mechanism. However, dosage adjustments based on the strain's MIC and the patient's renal function are crucial for optimal efficacy.
METHODS: MICs of temocillin and seven comparators (ertapenem, imipenem, meropenem, levofloxacin, delafloxacin, doxycycline and tigecycline) were determined using gradient strips for 104 3GC-R Enterobacterales isolates from BJIs in three French hospitals. Isolates were characterized about their mechanism of resistance to 3GC (ESBL or hyperproduced cephalosporinase). PK/PD simulations were performed with six dosage regimens and different stages of renal function in order to calculate PTA according to temocillin MIC.
RESULTS: Temocillin showed a susceptibility rate of 92.3% (96/104) in 3GC-R isolates from BJIs: 95.3% (61/64) in ESBL producers and 87.5% (35/40) in AmpC hyperproducers. Temocillin was the only alternative to carbapenems for 25% (26/104) of isolates. PTA values increased with declining renal function. In normorenal patients, none of the tested regimen achieved adequate PTA up to the Enterobacterales breakpoint (16 mg/L).
CONCLUSIONS: This study demonstrated the high in vitro efficacy of temocillin against 3GC-R Enterobacterales from BJIs, regardless of the underlying resistance mechanism. However, dosage adjustments based on the strain's MIC and the patient's renal function are crucial for optimal efficacy.