Læknablaðið - 15.01.1994, Blaðsíða 57

LÆKNABLAÐIÐ 1994; 80: 47-48
47
NÝR DOKTOR í LÆKNISFRÆÐI
SIGURÐIR GUÐMUNDSSON
Þann II. september 1993 varði Sigurður
Guðmundsson doktorsritgerð við læknadeild
Háskóla Islands. Ritgerðin nefnist The
postantibiotic effect, from tlie test tube to
the laboratory animal. Andmælendur voru
prófessor David Greenwood frá Nottingham
í Bretlandi og Karl G. Kristinsson læknir á
sýklarannsóknadeild Landspítalans. Agrip úr
ritgerðinni fer hér á eftir:
A previously poorly investigated
pharmacodynamic variable, the postantibiotic
effect (PAE), had been characterized by
several investigators in vitro for a number
of microorganisms and older antimicrobials.
In the work described herein the viable count
method for its determination was standardized
and enrployed to extend the initial data on the
PAE in vitro to a variety of extended spectrum
antimicrobials. Thus, by our observations and
those of others, cell-wall active antibiotics
(all four classes of (3 -lactams, vancomycin)
generally induce a PAE of 2-4 hrs duration
against Gram-positive organisms, but none
or very short PAE against Gram-negative
bacilli. Drugs that inhibit protein or nucleic
acid synthesis (aminoglycosides, trimethoprim,
tetracyclines, clindamycin, erythromycin,
chloramphenicol, 6-fluoroquinolones) induce
a PAE of I -6 hrs against both Gram-positive
cocci and Gram-negative bacilli. A notable
exception to the general absence of a PAE
after exposure of Gram-negative bacilli to
/3-lactams is the induction of a clinically
significant PAE by imipenem and other
carbapenems against P. aeruginosa.
PAEs up to 7-10 hrs were induced for
pathogenic yeasts (Candida albicans, C.
glabrata, Cryptococcus neofonnans) after
exposure to amphotericin B and 5-flucytosine,
but no true PAE was exhibited after exposure
of these organisms to imidazoles, only a
period of slower growth rate, presumably due
to the presence of residual drug.
In addition to parameters previously
demonstrated to influence the duration
of the PAE (type of antimicrobial and
microorganism, concentration of drug and its
duration of exposure), a significant deleterious
impact of pH and advantageous impact of
antimicrobial combinations, particularly from
the addition of rifampin, on the duration of
the PAE and bactericidal rate in vitro was
demonstrated.
The vast majority of data on the PAE have
been obtained by in vitro experimentation. In
vivo experiments in a neutropenic mouse thigh
infection model with a wide range of drug-
organism combinations have confirmed the
in vitro studies. However, the PAEs induced
by aminoglycosides against Gram-negative
bacilli were markedly longer in vivo than in
vitro and no in vivo PAE could be induced by