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Antimicrobial Agents and Chemotherapy, September 1999, p. 2320-2322, Vol. 43, No. 9
Servicio de Microbiología
Clínica, Hospital Clínico San Carlos, 28040 Madrid,
Spain
Received 11 March 1999/Returned for modification 13 May
1999/Accepted 29 June 1999
The antimicrobial activities of trovafloxacin, moxifloxacin,
sanfetrinem, quinupristin-dalfopristin, and 14 other antimicrobial agents against 218 Bacteroides fragilis group strains were
determined. A group of 10 imipenem-resistant strains were also tested.
Imipenem, meropenem, and sanfetrinem had the lowest MICs of all of the
Increasing resistance of
Bacteroides fragilis group bacteria to drugs commonly used
in the treatment of anaerobic infections, such as several This study aimed to ascertain the current susceptibility pattern of
these organisms in our hospital in order to detect trends and to
evaluate the activities of the new agents. We compared the in vitro
susceptibilities of recently isolated B. fragilis strains to
both newer (moxifloxacin, trovafloxacin, sanfetrinem, and
quinupristin-dalfopristin) and older antimicrobial agents (including
(Part of this study was presented at the 38th Interscience Conference
on Antimicrobial Agents and Chemotherapy, San Diego, Calif., 24 to 27 September 1998.)
The 218 clinical isolates of B. fragilis group bacteria
isolated in 1997 tested included the following numbers of isolates: B. fragilis, 133; B. thetaiotaomicron, 39;
B. uniformis, 26; B. caccae, 6; B. ovatus, 6; B. distasonis, 4; and B. vulgatus, 4. A group of 10 B. fragilis strains
(collected from 1989 to 1997) resistant to imipenem (MICs, 16 to >256
µg/ml) were also tested. Strains were identified by using the Rapid
ID 32A system (bioMérieux, Marcy l'Etoile, France). Sources
included skin and soft tissue (44.4%), abdomen (43.1%), blood
(8.2%), respiratory tract (1.8%), body fluid (1.4%), female genital
tract (0.9%), and bone (0.5%) samples.
Antimicrobial agents were obtained from the following companies:
trovafloxacin, ampicillin, and sulbactam, Pfizer, New York, N.Y.;
moxifloxacin, Bayer, Barcelona, Spain; sanfetrinem, Glaxo Wellcome,
Verona, Italy; quinupristin-dalfopristin and metronidazole, Rhône-Poulenc Rorer, Madrid, Spain; chloramphenicol, Zyma
Farmacéutica, Barcelona, Spain; clindamycin, Pharmacia & Upjohn,
Barcelona, Spain; cefoxitin and imipenem, Merck Sharp & Dohme, West
Point, Pa.; ceftizoxime, amoxicillin, ticarcillin, and clavulanate,
SmithKline Beecham Pharmaceuticals, Philadelphia, Pa.; cefminox,
Tedec-Meiji Farma, Madrid, Spain; piperacillin and tazobactam, Wyeth
Lederle, Pearl River, N.Y.
MICs were determined by the agar dilution method in accordance with
National Committee for Clinical Laboratory Standards (NCCLS) guidelines
(15).
The results of susceptibility testing are presented in Table
1. Trovafloxacin
displayed high levels of activity against members of the B. fragilis group, with 92 and 95% of the strains susceptible at 1 and 2 µg/ml, respectively. The in vitro activity of moxifloxacin was
comparable to that of trovafloxacin, with 94% of all strains inhibited
at 4 µg/ml. Trovafloxacin was slightly more active against B. thetaiotaomicron and B. uniformis than was
moxifloxacin. Sanfetrinem showed excellent activity, inhibiting 99.5%
of the strains at 4 µg/ml. The sanfetrinem MICs for 50 and 90% of
the strains tested (MIC50 and MIC90,
respectively) were comparable to those of the carbapenems and lower
than the MICs obtained with the other nine
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Activities of New Antimicrobial Agents (Trovafloxacin,
Moxifloxacin, Sanfetrinem, and Quinupristin-Dalfopristin) against
Bacteroides fragilis Group: Comparison with the Activities
of 14 Other Agents
ABSTRACT
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References
-lactams. Quinupristin-dalfopristin inhibited all of the strains at
2 µg/ml. Overall, the MICs of trovafloxacin and moxifloxacin for 90%
of the strains tested were 1 and 2 µg/ml, respectively.
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-lactam
agents or clindamycin, has been reported in the last 2 decades (5,
7, 10, 18, 19). Effective alternative antimicrobials with
antianaerobic activity have become necessary. The older quinolones have
a wide antibacterial spectrum and potential bactericidal activity
against aerobic bacteria but have poor activity against anaerobes.
Several newer quinolones, such as trovafloxacin and moxifloxacin,
possess a broad antimicrobial spectrum which covers gram-positive and
gram-negative bacteria. They are also effective against anaerobes.
Sanfetrinem is the first member of a new class of tricyclic -lactam
compounds, the trinems (previously tribactams). Two publications
(4, 9) have demonstrated that sanfetrinem possesses a broad
spectrum of activity, which includes gram-negative and gram-positive
aerobes and anaerobes, and exhibits high potency and stability against many -lactamases. Quinupristin-dalfopristin is a semisynthetic injectable streptogramin with significant activity against
gram-positive organisms and marked antianaerobic activity.
-lactam antibiotics, -lactam--lactamase inhibitor combinations, and non--lactam agents).
-lactams tested. Overall,
metronidazole and quinupristin-dalfopristin were the most active
agents; both inhibited all strains at 2 µg/ml. For the cephamycins
and piperacillin, there was variability in the susceptibility rates
when MICs within 1 or 2 dilutions of the breakpoint were considered.
Cefoxitin inhibited 70.6, 87.2, and 96.3% of the isolates at 16, 32, and 64 µg/ml, respectively. Within the group, B. fragilis
strains were more susceptible to the cephalosporins tested than were
the other species of the group. Cefoxitin and cefminox exhibited
similar activities against B. fragilis strains, and
ceftizoxime was markedly more active. In our hospital, the rate of
resistance to clindamycin has remained at about 30 to 33% since 1994. We found one B. fragilis strain that was highly resistant to
all of the -lactam antibiotics, either alone or in combination with
a -lactamase inhibitor.
TABLE 1.
In vitro effectiveness of antimicrobial agents against
the B. fragilis group
Metronidazole and chloramphenicol were uniformly effective against all
of the imipenem-resistant isolates tested. Six of these strains were
also highly resistant to clindamycin. Trovafloxacin and
moxifloxacin showed excellent activity against imipenem-resistant strains. Quinupristin-dalfopristin inhibited these strains at a
concentration of 
1 µg/ml, while sanfetrinem yielded high MICs (range, 32 to 256 µg/ml).
In general, with the old antibiotics, our results are similar to those
found in other studies in Spain (6, 12) and other countries
(1, 10, 13, 18, 19). Resistance to the carbapenems and
-lactam--lactamase inhibitor combinations has been detected in our hospital since 1989 but with a very low incidence (0.5 to
1.5%). Several researchers have reported low rates of resistance to
imipenem (1, 10, 18, 20). By comparing the results of this
study with those of previous susceptibility studies reported by our
group for isolates recovered between 1979 and 1995 (7, 8),
we found that there were no significant changes in the overall
susceptibility patterns during the last 5 years.
Our results confirm the previous finding that quinupristin-dalfopristin has good in vitro activity against B. fragilis group organisms (16), although the quinupristin-dalfopristin MICs we obtained were slightly lower than those reported by Appelbaum et al. (3). Sanfetrinem appears to have excellent activity against B. fragilis group bacteria, as described previously by Di Modugno et al. (9) for B. fragilis strains. Our study shows high activity of trovafloxacin and moxifloxaxcin against B. fragilis group isolates, including those resistant to imipenem. Other studies (17, 20) have yielded values similar to ours for trovafloxacin. Several investigators (2, 11, 14) have also reported excellent activity of moxifloxacin against the B. fragilis group.Moxifloxacin and trovafloxacin MICs for B. fragilis strains were lower than those seen for B. thetaiotaomicron and B. uniformis strains, as reported elsewhere (2, 17, 20).
There are geographic variations and changes over time in the
susceptibilities of B. fragilis group organisms to different antimicrobials. The increased incidence among B. fragilis group bacteria to some antimicrobial agents, such
as clindamycin or cephamycins, and the emergence of resistance to
imipenem and -lactam--lactamase inhibitor combinations require
periodic susceptibility studies and the development of new
broad-spectrum drugs. Given the excellent in vitro activity of
trovafloxacin and moxifloxacin and their broad spectrum of activity, we
suggest that both of them be considered as single agents in the
treatment and prophylaxis of mixed aerobic-anaerobic infections
involving B. fragilis group organisms. This study also confirms the excellent in vitro activity of sanfetrinem and
quinupristin-dalfopristin against the B. fragilis
group. Both the quinolones tested and the new streptogramin
may play a potential role in the treatment of infections caused by
imipenem-resistant B. fragilis strains and would also be a
therapeutic option for patients allergic to -lactams. Clinical
studies will determine the therapeutic efficacy of the new agents
tested. As it is not known whether resistant strains will emerge during
therapy, B. fragilis group bacteria should be periodically
monitored for the emergence of resistance to these new drugs.
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FOOTNOTES |
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* Corresponding author. Mailing address: Servicio de Microbiología Clínica, Hospital Clínico San Carlos, Plaza Cristo Rey s/n, 28040 Madrid, Spain. Phone: 341 3303486. Fax: 341 3303478. E-mail: cbetriu{at}efd.net.
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Antimicrobial Agents and Chemotherapy, September 1999, p. 2320-2322, Vol. 43, No. 9
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Copyright © 1999, American Society for Microbiology. All rights reserved.
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