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Antimicrobial Agents and Chemotherapy, April 1999, p. 983-984, Vol. 43, No. 4
Servicio de Bacteriología, Centro
Nacional de Microbiología, Instituto de Salud Carlos III,
28220 Majadahonda, Madrid, Spain
Received 17 July 1998/Returned for modification 10 November
1998/Accepted 25 January 1999
In vitro activities of the ketolides HRM 3647 and HRM 3004 against
pathogenic Neisseria gonorrhoeae and N. meningitidis, saprophytic Neisseria isolates, and
Moraxella catarrhalis were determined. The comparison of
ketolide activities with those of the other macrolides shows a much
better activity in the majority of species, with macrolide MICs at
which 90% of the isolates are inhibited between 8- and 10-fold higher.
Ketolides are a new class of
semisynthetic 14-member ring macrolides which differ from
erythromycin A in that they have a 3-keto group on the erythronolide A
ring instead of an L-cladinose (2).
Ketolides have in vitro activities against many multi-drug-resistant (especially erythromycin-resistant strains) gram-positive organisms, including staphylococci, enterococci, and pneumococci; some anaerobes; Haemophilus spp.; and other fastidious strains
(1, 3-6, 8).
In this study we compare the in vitro activities of ketolides HRM 3647 and HRM 3004 with those of erythromycin, other macrolides, and
quinolones against pathogenic Neisseria gonorrhoeae and
N. meningitidis and saprophytic Neisseria
isolates and Moraxella catarrhalis. A total of 600 isolates
of Neisseria spp. and M. catarrhalis received
from the collection of the National Center for Microbiology of
Spain or from hospital laboratories between 1994 and 1997 were studied.
Antimicrobial agents supplied as laboratory powders of known
potency were as follows: HRM 3004, HRM 3647, erythromycin,
clarithromycin, roxithromycin, azithromycin, ciprofloxacin,
ofloxacin, levofloxacin (Hoecht-Marion-Roussel, Romainville,
France) and sparfloxacin (Rhône-Poulenc-Rorer, Vitry,
France). In vitro activities were determined by the agar dilution
method according to National Committee for Clinical Laboratory
Standards guidelines (7). The medium employed was
Mueller-Hinton agar, except for gonococci, for which GC medium (Difco)
was used. The inocula were directly prepared from an
overnight culture in Mueller-Hinton agar or GC medium (gonococci). A standard inoculum to obtain 104 to
105 CFU/spot was prepared and applied to agar plates
containing antibiotics by using a Denley multipoint inoculator (Cultek,
Madrid, Spain). All plates were incubated at 37°C for 18 h in a
5% CO2 atmosphere. The MIC was defined as the lowest
concentration at which no growth was visible on agar plates. The
following reference organisms were included for quality
control: Staphylococcus aureus ATCC 29213 and N. gonorrhoeae ATCC 49226.
Table 1 shows the
antimicrobial activities of ketolides (HMR 3004 and HMR 3647)
compared with those of other antibiotics (macrolides and quinolones)
tested against 600 strains of Neisseria spp. and M. catarrhalis.
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
In Vitro Activities of Ketolides HRM 3647 and HRM 3004, Levofloxacin, and Other Quinolones and Macrolides against
Neisseria spp. and Moraxella
catarrhalis
ABSTRACT
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TABLE 1.
Activities of HMR 3004 and HMR 3647 compared to those of
levofloxacin and other quinolones and macrolides against
Neisseria spp. and
Moraxella catarrhalis
N. gonorrhoeae and N. meningitidis were very
susceptible to the ketolides (MICs at which 90% of the isolates are
inhibited [MIC90s], 0.12 µg/ml). M. catarrhalis shows similar features, whereas saprophytic
Neisseria isolates, for which MIC90s were 4 µg/ml (range, 0.25 [N. polysaccharea] to 4 [N.
mucosa, N. perflava/sicca]), showed significantly
decreased susceptibility. The MICs of the two ketolides for the
different species were similar, and no significant differences were
encountered between the various patterns of isolates studied in each
species. Also, no differences were found between ketolide MICs for
-lactamase-producing or -nonproducing M. catarrhalis and those for pathogenic Neisseria isolates
moderately resistant or susceptible to penicillin.
Comparison of ketolide activity with those of the other macrolides showed a much better activity in the majority of species, with macrolide MIC90s between 8- and 10-fold higher, except MICs for M. catarrhalis, which were similar to those of the ketolides. The ketolide MICs obtained by us for Neisseria isolates and M. catarrhalis were similar to those reported by other researchers (4-6). All the species tested except M. catarrhalis were more susceptible to quinolones than to ketolides and macrolides. The MIC90s of the two types of compounds for M. catarrhalis were very similar.
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ACKNOWLEDGMENTS |
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This study was supported by grants from Hoechst-Marion-Roussel, France, and from the Fondo de Investigaciones Sanitarias de la Seguridad Social (FISS 95/0388), the Ministry of Health, Spain.
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FOOTNOTES |
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* Corresponding author. Mailing address: Servicio de Bacteriología, Centro Nacional de Microbiología, Instituto de Salud Carlos III, 28220 Majadahonda, Madrid, Spain. Phone: 34-1-5097901. Fax: 34-1-5097966. E-mail: jasaez{at}isciii.es.
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Antimicrobial Agents and Chemotherapy, April 1999, p. 983-984, Vol. 43, No. 4
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