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2017 ; 64
(11
): 1582-1588
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The Lysis of Pathogenic Escherichia coli by Bacteriophages Releases Less
Endotoxin Than by ?-Lactams
#MMPMID28329379
Dufour N
; Delattre R
; Ricard JD
; Debarbieux L
Clin Infect Dis
2017[Jun]; 64
(11
): 1582-1588
PMID28329379
show ga
BACKGROUND. Other than numerous experimental data assessing phage therapy
efficacy, questions regarding safety of this approach are not sufficiently
addressed. In particular, as phages can kill bacterial cells within <10 minutes,
the associated endotoxin release (ER) in severe infections caused by
gram-negative bacteria could be a matter of concern. METHODS. Two therapeutic
virulent phages and 4 reference antibiotics were studied in vitro for their
ability to kill 2 pathogenic strains of Escherichia coli and generate an ER. The
early interaction (first 3 hours) between these actors was assessed over time by
studying the instantaneous cell viability, the colony-forming unit count, the
concentration of free endotoxin released, and the cell morphology under light
microscope. RESULTS. While ?-lactams have a relatively slow effect, both tested
phages, as well as amikacin, were able to rapidly abolish the bacterial growth.
Even when considering the fastest phage (cell lysis in 9 minutes), the
concentrations of phage-induced ER never reached the highest values, which were
recorded with antibiotic treatments. Cumulative concentrations of endotoxin over
time in phage-treated conditions were lower than those observed with ?-lactams
and close to those observed with amikacin. Whereas ?-lactams were responsible for
strong cell morphology changes (spheroplast with imipenem, filamentous cells with
cefoxitin and ceftriaxone), amikacin and phages did not modify cell shape but
produced intracellular inclusion bodies. CONCLUSIONS. This work provides
important and comforting data regarding the safety of phage therapy.
Therapeutically relevant phages, with their low endotoxin release profile and
fast bactericidal effect, are not inferior to ?-lactams.