Unit:
Τομέας ΠαθολογίαςLibrary of the School of Health Sciences
Author:
Κωνσταντινίδου Ελευθερία
Dissertation committee:
Γιαμαρέλλου Ελένη Καθηγήτρια Παθολογίας, Βώρος Διονύσιος Καθηγητής Χειρουργικής, Πετρίκκος Γεώργιος Καθηγητής Παθολογίας, Δαϊκος Γεώργιος Καθηγητής Λοιμωξιολογίας, Παπαδόπουλος Ιορδάνης Καθηγητής Χειρουργικής, Σουλή Μαρία Επίκουρη Καθηγήτρια Παθολογίας, Αντωνιάδου Αναστασία Επίκουρη Καθηγήτρια Παθολογίας
Original Title:
Μελέτη της αποτελεσματικότητας των καρβαπενεμών εναντίον κλινικού στελέχους που παράγει μέταλλο-β-λακταμάση σε πειραματικό μοντέλο ενδοπεριτοναϊκού αποστήματος.
Translated title:
Study of the efficacy of carbapenems against a metallo-β-lactamase producing clinical isolate in an experimental intra-abdominal abscess model
Summary:
Although metallo-b-lactamases (MBLs) hydrolyze most b-lactams including
carbapenems, MBL-producing Enterobacteriaceae very often remain susceptible to
carbapenems in vitro. Given this, we studied the in vivo efficacy of imipenem,
meropenem, ertapenem and aztreonam against a carbapenem-susceptible
MBL-producing clinical Escherichia coli strain in a rabbit intra-abdominal
abscess model.
Methods: Rabbits were inoculated intraperitoneally with 108 cfu/ml of
VIM-1-positive E. coli and were assigned to receive no treatment (controls) or
intravenous 1) imipenem/cilastatin (imipenem) 70 mg/kg/12h 30 min infusion or
2) meropenem 125 mg/kg/12h 10 min infusion or 3) ertapenem 60 mg/kg/12h bolus
or 4) aztreonam 70 mg/kg/12h bolus. Dosing regimens were chosen on the basis of
preliminary pharmacokinetic studies, so that T>MIC was achieved for 50% of the
dosing interval for all tested antibiotics. A total of eight doses were
administered before sacrifice and the abscesses were harvested and
quantitatively cultured.
Results: MICs of imipenem, meropenem, ertapenem and aztreonam for the infecting
isolate were 1, 0.25, 1.5 and 0.25 mg/L, respectively. The log10 cfu/g
(mean±SD) of viable counts in pus was as follows: controls (n=16), 8.71±1.34
(P<0.001 versus all other groups); imipenem (n=15), 4.89±2.42; meropenem
(n=15), 4.24±2.44; ertapenem (n=16), 3.17±1.85 (P=0.022 versus imipenem); and
aztreonam (n=15), 3.62±3.05. Mortality among treated rabbits was significantly
reduced compared with controls. Four animals in the aztreonam group (26.7%) had
culture-negative pus and no mortality was noted among aztreonam-treated animals.
Conclusions: In the rabbit experimental model carbapenems were shown to be
effective in the treatment of intra-abdominal infection due to an
extended-spectrum b-lactamase-negative carbapenem-susceptible VIM-1-producing
clinical E. coli strain, but treatment with aztreonam resulted in a more
favourable outcome overall.
Keywords:
carbapenems, metallo-b-lacatamases, enterobacteriacae, intra-abdominal abscess, E.coli, experimental model
Number of references:
332