Temocillin: a therapeutic alternative in bone and joint infections due to third generation cephalosporin-resistant Enterobacterales?

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.