This paper discusses the evaluation of new
macrolides and new
quinolones for the treatment of
Legionnaires' disease in in vitro susceptibility test, penetration to polynuclear leukocytes and treatment in an animal model. Some kinds of
biological response modifier (BRMs) such as
granulocyte colony stimulating factor (GCSF), monocyte
CSF (M-
CSF), GM-CSF, recombinant
interleukin-1 (IL-1) and
IL-2 were also evaluated. The antimicrobial activity (MIC) of new
macrolides to Legionella pneumophila (45 strains) showed the highest activity in
TE-031 (Taisho
Pharmaceutical Co., Tokyo, Japan) and then
rokitamycin (RKM),
RU-28965 (Roussel, France),
erythromycin (EM),
josamycin (JM) in decreasing order of activity. According to the results of the data of cell-penetration and survival rate
after treatment of guinea pigs with experimental Legionella
pneumonia, the new
macrolides such as
TE-031, RKM and
RU-28965 are expected to be more effective in the treatment of
Legionnaires' disease than EM. New
quinolones such as ciprofloxatin (CPFX),
NY-198 (Hokuriku
Pharmaceutical Co., Japan) or
T-3262 (Toyama Kagaku
Pharmaceutical Co., Toyama Japan) were compared to
ofloxacin (OFLX),
enoxacin (ENX) or
rifampin (RFP) for evaluation. These drugs showed excellent activity against L. pneumophila and good penetration to polynuclear leukocytes. Regarding the treatment of guinea pig with legionella
pneumonia, OFLX was the most effective, and
NY-198 or
T-3262 were more effective than EM treatment. The highest survival rate was obtained with
IL-2 in infected guinea pigs. We also observed the efficacy of combined use of
IL-2 and HR-8 10 (Horchst FRG) which is a newly developed cephem
antibiotic.(ABSTRACT TRUNCATED AT 250 WORDS)