Vol. 35, No. 3
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Mar. 1991, p. 594-599 0066-4804/91/030594-06$02.00/0 Copyright C) 1991, American Society for Microbiology
Susceptibility of Anaerobic Bacteria to BAY
v
3522
CARL ERIK NORD,'* MARGARETA RYLANDER,2 AND S. RAGNAR NORRBY3 Department of Microbiology, Huddinge University Hospital,' and Department of Clinical Microbiology, Karolinska Hospital,2 Karolinska Institute, Stockholm, and Department of Infectious Diseases, Lund University Hospital, University of Lund, Lund,3 Sweden Received 31 August 1990/Accepted 17 December 1990
The activity of BAY v 3522 against 340 strains of anaerobic bacteria was determined by an agar dilution method. Its activity was compared with those of amoxicillin, amoxicillin-clavulanate, cefaclor, cefadroxil, cefoxitin, cefuroxime, cephalexin, clindamycin, doxycycline, and metronidazole. BAY v 3522, amoxicillinclavulanate, cefoxitin, clindamycin, and metronidazole were the most active agents tested. On the basis of these results, BAY v 3522 appears to have an antibacterial activity that warrants further investigation in clinical trials.
BAY v 3522 is a new oral cephalosporin which has the following formula: 7-[D-2-amino-2-(2-aminobenzothiazol-6yl)-acetamido]-3-[(Z)-1-propen-1-yl]-3-cephem-4-carboxylic acid monohydrate. It is produced by Bayer AG, Wuppertal, Federal Republic of Germany. The purpose of the present investigation was to determine the in vitro activity of BAY v 3522 against anaerobic bacteria recently isolated from respiratory tract and wound infections. Its activity was compared with those of amoxicillin, amoxicillin-clavulanate, cefaclor, cefadroxil, cefoxitin, cefuroxime, cephalexin, clindamycin, doxycycline, and metronidazole. All strains were identified by the criteria of Holdeman et al. (2). The antimicrobial susceptibility tests were performed by the method of Dornbusch et al. (1). The strains were grown in rubber-stoppered tubes containing prereduced chopped meat broth with glucose. Antimicrobial susceptibility testing was performed on PDM-ASM agar (AB Biodisk, Solna, Sweden), with the addition of 5% defibrinated horse blood, by the agar dilution method. Inocula were 48-h cultures diluted 10-2 in prereduced Proteose Peptone broth (Difco Laboratories, Detroit, Mich.). This dilution resulted in 105 CFU per spot, when the bacteria were applied with a modified Steers replicator to freshly prepared agar plates containing the appropriate antimicrobial agent. An agar plate without an antimicrobial agent was always included as a growth control. The colony counts were checked after each inoculation. The plates were read after 48 h of incubation at 37°C in anaerobic jars (GasPak; BBL Microbiology Systems, Cockeysville, Md.). The MIC was defined as the lowest concentration of the drug that inhibited growth. The appearance of a single colony or of a barely visible haze was disregarded. The presence of ,B-lactamase was determined by the nitrocefin disk assay. The break points, in milligrams per liter, for the following antimicrobial agents were used, as recommended by the National Committee for Clinical Laboratory Standards (3): amoxicillin-clavulanate, 16/8; cefoxitin, 16; clindamycin, 2; tetracycline, 8; and metronidazole, 16. Three control microorganisms were used for monitoring the susceptibility tests: Bacteroidesfragilis ATCC 25285, Bacteroides thetaiotaomicron ATCC 29741, and Clostridium perfringens ATCC
their respective manufacturers: amoxicillin and clavulanate, Astra Clinical Research Centre (Sodertalje, Sweden); cefaclor, Eli Lilly & Co. (Indianapolis, Ind.); cefadroxil, Bristol-Myers Int. (New York, N.Y.); cefoxitin, Merck Sharp & Dohme (Rahway, N.J.); cefuroxime and cephalexin, Glaxo (Greenford, United Kingdom); clindamycin, The Upjohn Co. (Kalamazoo, Mich.); doxycycline, Pfizer Inc. (New York, N.Y.); and metronidazole, Rhone-Poulenc Sante (Paris, France). The in vitro activities of BAY v 3522 and the other antimicrobial agents against the anaerobic bacteria tested are given in Table 1. All anaerobic cocci were highly susceptible to BAY v 3522, amoxicillin, amoxicillin-clavulanate, clindamycin, doxycycline, and metronidazole, while higher MICs for cefaclor, cefadroxil, cefoxitin, cefuroxime, and cephalexin were observed. BAY v 3522, amoxicillin, amoxicillin-clavulanate, clindamycin, and doxycycline were the most active drugs against Propionibacterium acnes strains. These agents were more active against P. acnes than were cefaclor, cefadroxil, cefoxitin, cefuroxime, and cephalexin. All strains were resistant to metronidazole. Ninety percent of C. perfringens isolates were inhibited by 0.032 mg of BAY v 3522 and amoxicillin per liter; 0.064 mg of amoxicillin-clavulanate per liter; 0.125 mg of doxycycline per liter; 1.0 mg of cefoxitin, cefuroxime, clindamycin, and metronidazole per liter; 4.0 mg of cefaclor per liter; and 8.0 mg of cefadroxil and cephalexin per liter. Many ,3-lactamase-producing strains in the Bacteroides fragilis group (B. fragilis, B. uniformis, B. ovatus, B. vulgatus, B. thetaiotaomicron, and B. distasonis) were resistant to six of the beta-lactam antibiotics tested (MIC, >16 mg/liter). All strains were susceptible to the combination amoxicillin-clavulanate. Ten percent of the B. fragilis and B. uniformis strains were resistant to cefoxitin. All isolates were susceptible to metronidazole, whereas 10% of the B. fragilis strains were resistant to clindamycin and doxycycline, and 10% of the B. distasonis isolates were resistant to
doxycycline. For the strains in the non-B. fragilis group (B. asaccharolyticus, B. bivius, B. disiens, B. intermedius, B. melaninogenicus, and B. ruminicola), which were ,B-lactamase positive, MICs of the beta-lactam antibiotics tested were higher than those for the P-lactamase-negative strains, except for that of amoxicillin-clavulanate. However, only B. asaccharolyticus strains were found to be resistant to amoxicillin
13124. The following antimicrobial agents were obtained from *
Corresponding author. 594
VOL. 35, 1991
NOTES
595
TABLE 1. Comparative in vitro activities of BAY v 3522 and other antimicrobial agents against anaerobic bacteria Microorganism
(no. of isolates) Anaerobic cocci (50)c
Propionibacterium acnes (30)
Clostridium perfringens (30)
Bacteroides fragilis (61 P-lactamase-positive and 5 P-lactamase-negative strains)
Antimicrobial agent BAY v 3522 Amoxicillin Amoxicillin-clavulanate Cefaclor Cefadroxil Cefoxitin Cefuroxime Cephalexin Clindamycin Doxycycine Metronidazole
0.008-2.0 0.008-0.5 0.008-0.5 0.008-32 0.125-16 0.064-8.0 0.064-8.0 0.008-32 0.016-1.0 0.032-1.0 0.125-8.0
BAY v 3522 Amoxicillin Amoxicillin-clavulanate Cefaclor Cefadroxil Cefoxitin Cefuroxime Cephalexin Clindamycin Doxycycline Metronidazole
SO0o
90to
0.125 0.064 0.125 1.0 1.0 1.0 0.25 1.0 0.064 0.125 4.0
1.0 0.25 0.25 4.0 4.0 4.0 4.0 4.0 0.064 0.5 4.0
0.008-0.5 0.016-0.125 0.125-0.25 0.008-4.0 0.008-1.0 0.032-1.0 0.032-0.5 0.008-2.0 0.016-0.064 0.125 32->64
0.064 0.064 0.064 1.0 0.5 0.125 0.125 1.0 0.016 0.125 >64
0.25 0.125 0.125 2.0 0.5 0.25 0.25 1.0 0.032 0.125 >64
BAY v 3522 Amoxicillin Amoxicillin-clavulanate Cefaclor Cefadroxil Cefoxitin Cefuroxime Cephalexin Clindamycin Doxycycline Metronidazole
0.008-0.032 0.008-0.064 0.008-0.064 0.008-4.0 0.125-8.0 0.064-1.0 0.064-2.0 0.25-16 0.008-1.0 0.008-16 1.0-4.0
0.016 0.008 0.008 0.5 0.5 0.5 0.125 1.0 0.125 0.064 1.0
0.032 0.032 0.064 4.0 8.0 1.0 1.0 8.0 1.0 0.125 1.0
BAY v 3522 (+)d BAY v 3522 (-)d Amoxicillin (+) Amoxicillin (-)
2.0->16 16 8.0->16 16 0.25-4.0 0.25-1.0 1.0->128 64 ->128 2.0->128 8.0-128 1.0-32 1.0-16 4.0->16 16->16 4.0->128 16-128 0.016-2.0 0.25->8.0 0.25-2.0
Amoxicillin-clavulanate (+) Amoxicillin-clavulanate (-) Cefaclor (+) Cefaclor (-) Cefadroxil (+) Cefadroxil (-) Cefoxitin (+) Cefoxitin (-) Cefuroxime (+) Cefuroxime (-) Cephalexin (+) Cephalexin (-) Clindamycin Doxycycline Metronidazole Bacteroides uniformis (5 ,B-lactamase-positive and 3 P-lactamase-negative strains)
MIC (mg/liter)a
Range
BAY v 3522 (+) BAY v 3522 (-) Amoxicillin (+) Amoxicillin (-)
Amoxicillin-clavulanate (+) Amoxicillin-clavulanate (-) Cefaclor (+) Cefaclor (-) Cefadroxil (+) Cefadroxil (-) Cefoxitin (+)
16 16 16 16 0.5 0.5 64 128 16 16 8.0 8.0 16 >16 16 16 0.5 0.5 0.5
>16 16 >16 16 1.0 1.0 >128 >128 128 128 16 16 >16 >16 32 128 2.0 >8.0 1.0
4.0 4.0-16 8.0 0.25-4.0 0.5 4.0-64 32-64 8.0
16 4.0 8.0 8.0 0.5 0.5 32 64 8.0
8.0-16 1.0-32
8.0 8.0
>16 4.0 16 8.0 4.0 0.5 64 64 8.0 16 16
4.0-16
%
Resistantb 0 0 0 0 0 00 0 0
0 0 100 0 0
0 0 10 0
90 0 0 0
10 0
,10 10 0
0 0 0 0
10
Continued on following page
596
ANTIMICROB. AGENTS CHEMOTHER.
NOTES TABLE 1-Continued
Microorganism (no. of isolates)
MIC
Antimicrobial agent Cefoxitin (-) Cefuroxime (+)
Cefuroxime (-) Cephalexin (+) Cephalexin (-) Clindamycin Doxycycline Metronidazole Bacteroides ovatus (7 P-lactamase-positive strains and 1 P-lactamase-negative strain)
BAY v 3522 (+) BAY v 3522 (-) Amoxicillin (+) Amoxicillin (-) Amoxicillin-clavulanate (+) Amoxicillin-clavulanate (-) Cefaclor (+) Cefaclor (-) Cefadroxil (+) Cefadroxil (-) Cefoxitin (+) Cefoxitin (-) Cefuroxime (+) Cefuroxime (-) Cephalexin (+) Cephalexin (-) Clindamycin
Doxycycline Metronidazole Bacteroides vulgatus (2 P-lactamase-positive strains and 1
,-lactamase-negative strain)
BAY v 3522 (+) BAY v 3522 (-) Amoxicillin (+) Amoxicillin (-)
Amoxicillin-clavulanate (+) Amoxicillin-clavulanate (-) Cefaclor (+) Cefaclor (-) Cefadroxil (+) Cefadroxil (-) Cefoxitin (+) Cefoxitin (-) Cefuroxime (+) Cefuroxime (-) Cephalexin (+) Cephalexin (-)
Clindamycin Doxycycline Metronidazole Bacteroides thetaiotaomicron
(7 ,B-lactamase-positive strains)
BAY v 3522 Amoxicillin Amoxicillin-clavulanate Cefaclor Cefadroxil Cefoxitin Cefuroxime
Cephalexin Clindamycin Doxycycline Metronidazole Bacteroides distasonis (7 13-lactamase-positive strains and 1 ,-lactamase-negative strain)
(mg/liter)a
%
9%%
Range 1.0-16 2.0->16 2.0-4.0 8.0-16 16-32 0.032-1.0 0.25-8.0 0.5
50%
2.0->16 16 8.0-16 16 0.5-1.0 0.5 1.0-128 >128 4.0-128 16 1.0-16 16 1.0->16 8.0 1.0-128 16 0.125-2.0 0.25-2.0 0.5-2.0
16 16 16 16 0.5 0.5 128 >128 16 16 8.0 16 >16 8.0 16 16 1.0 0.25 1.0
>16 16 >16 16 1.0 0.5 >128 >128 128 16 16 16 >16 8.0 128 16 2.0 2.0 2.0
>16 2.0 16 2.0 0.5 0.5 8.0-128 >128 1.0-16 64 1.0-8.0 8.0 16->16 16 8.0-32 16 0.5-1.0 0.5-2.0 0.5-1.0
>16 2.0 16 2.0 0.5 0.5 8.0 >128 1.0 64 8.0 8.0 16 16 8.0 16 0.5 2.0 1.0
>16 2.0 16 2.0 0.5 0.5 128 >128 16 64 8.0 8.0 >16 16 32 16 1.0 2.0 1.0
>16 16 1.0 >128 16 8.0 >16 16 1.0 2.0 0.5
>16 >16 1.0 >128 >128 16 >16 >128 2.0 4.0 1.0
>16 8.0->16 0.5-1.0 1.0->128 16->128 1.0-16 >16 1.0->128 0.25-2.0 0.25-4.0 0.5-1.0
BAY v 3522 (+) BAY v 3522 (-) Amoxicillin (+) Amoxicillin (-)
8.0->16 8.0 8.0->16 8.0
Amoxicillin-clavulanate (+) Amoxicillin-clavulanate (-)
0.5-1.0 0.25
8.0 8.0 2.0 8.0 16 0.125 0.5 0.5
>16 8.0 16 8.0 1.0 0.25
16 >16 4.0 16 32 1.0 8.0 0.5
>16 8.0 >16 8.0 1.0 0.25
Resistantb eitn 0
0 0 0
10 0 0 0
0 0
0 0 0
0 0 0 0
0 0
0 0 100
10 0 0 0 0
10 0 0 0
Continued on following page
VOL. 35, 1991
NOTES
597
TABLE 1-Continued Microorganism (no. of isolates)
Bacteroides asaccharolyticus (5 P-lactamase-positive and 5
1-lactamase-negative strains)
Bacteroides bivius (15 ,B-lactamase-positive and 10 1-lactamase negative strains)
MIC (mg/liter)a
Antimicrobial agent
Range
90Po
>128 64 16 8.0 8.0 8.0 >16 16 16 16 0.5 0.5 0.5
>128 64 >128 8.0 8.0 8.0 >16 16 >128 16 2.0 >8.0 1.0
Cefaclor (+) Cefaclor (-) Cefadroxil (+) Cefadroxil (-) Cefoxitin (+) Cefoxitin (-) Cefuroxime (+) Cefuroxime (-) Cephalexin (+) Cephalexin (-) Clindamycin Doxycycline Metronidazole
2.0->128 64 16->128 8.0 1.0-16 8.0 16 ->16 16 8.0->128 16 0.032-2.0 0.25->8.0 0.25-1.0
BAY v 3522 (+) BAY v 3522 (-) Amoxicillin (+) Amoxicillin (-) Amoxicillin-clavulanate (+) Amoxicillin-clavulanate (-) Cefaclor (+) Cefaclor (-) Cefadroxil (+) Cefadroxil (-) Cefoxitin (+) Cefoxitin (-) Cefuroxime (+) Cefuroxime (-) Cephalexin (+) Cephalexin (-)
0.008->16 0.008-1.0 0.032->16 0.032-0.5 0.032-2.0 0.032-1.0 0.008->128 0.008-4.0 0.125-64 0.125-8.0 0.064-1.0 0.064-0.5 0.064->16 0.064-4.0 0.125-64 0.125-4.0 0.016-0.25 0.032->16 0.064->64
1.0 0.25 0.5 0.125 0.25 0.25 1.0 0.5 0.5 0.25 0.5 0.125 2.0 0.125 1.0 0.25 0.016 0.125 1.0
8.0 1.0 4.0 0.25 2.0 1.0 4.0 1.0 32 0.5 1.0 0.5 8.0 1.0 64 1.0 0.016 16 1.0
0.008->16 0.008-0.25 0.5-16 0.016-0.25 0.125-2.0 0.032-0.5 0.008-64 0.016-4.0 0.016-64 0.032-8.0 0.064-4.0 0.016-1.0 0.032-16 0.016-2.0 0.032-64 0.008-4.0 0.008-0.25 0.125-16 0.064-4.0
2.0 0.125 8.0 0.125 0.25 0.25 2.0 0.5 1.0 0.5 1.0 0.125 1.0 0.125 1.0 0.125 0.016 0.125 1.0
16 0.25 16 0.25 1.0 0.5 8.0 2.0 32 1.0 4.0 0.25 8.0 1.0 32 2.0 0.032 16 2.0
0.016-16 0.016-0.5 0.032-32 0.016-0.5 0.016-2.0 0.016-0.5 0.008-64 0.008-2.0 0.032-32 0.032-4.0 0.032-4.0
1.0 0.125 8.0 0.125 0.5 0.125 4.0 1.0 2.0 0.25
4.0 0.25 16 0.25
0.016-0.5 0.016-32
0.25 2.0
Clindamycin Doxycycline Metronidazole BAY v 3522 (+) BAY v 3522 (-) Amoxicillin (+) Amoxicillin (-)
Amoxicillin-clavulanate (+) Amoxicillin-clavulanate (-) Cefaclor (+) Cefaclor (-) Cefadroxil (+) Cefadroxil (-) Cefoxitin (+) Cefoxitin (-) Cefuroxime (+) Cefuroxime (-) Cephalexin (+) Cephalexin (-) Clindamycin Doxycycline Metronidazole Bacteroides disiens (13 j-lactamase-positive and 12 P-1actamase-negative strains)
%
50to
BAY 3522 (+) BAY 3522 (-) Amoxicillin (+) v
v
Amoxicilin
(-)
Amoxicillin-clavulanate
(+)
Amoxicillin-clavulanate
(-)
Cefaclor (+) Cefaclor (-) Cefadroxil (+) Cefadroxil (-) Cefoxitin (+) Cefoxitin (-) Cefuroxime (+)
1.0
1.0
0.25 8.0 2.0 16 0.5 2.0 0.5 8.0
Resistantb
0 0
0 10 0
4 0 0 0
0 0
0 10 10
0 0 0 0
0 0
0 10 0
10 0 0 0
0 0
Continued on following page
598
NOTES
ANTIMICROB. AGENTS CHEMOTHER.
TABLE 1-Continued Microorganism (no. of isolates)
Antimicrobial agent
50%o
901J
0.008-1.0 0.125-32 0.032-2.0 0.016-0.25 0.125-16 0.125-2.0
0.25 2.0 0.25 0.032 0.2 0.5
0.5 16 0.5 0.125 16 1.0
0.064 0.016 0.016 0.5 0.25 0.125 0.25 0.5 0.032 0.5 0.5
0.5 0.125 0.125 2.0 2.0 0.25 2.0 4.0
Metronidazole
0.008-1.0 0.008-0.5 0.008-0.5 0.008-4.0 0.008-4.0 0.008-1.0 0.008-4.0 0.008-4.0 0.016-0.5 0.016-8.0 0.125-4.0
BAY v 3522 (+) BAY v 3522 (-) Amoxicillin (+) Amoxicillin (-) Amoxicillin-clavulanate (+) Amoxicillin-clavulanate (-) Cefaclor (+) Cefaclor (-) Cefadroxil (+) Cefadroxil (-) Cefoxitin (+) Cefoxitin (-) Cefuroxime (+) Cefuroxime (-) Cephalexin (+) Cephalexin (-) Clindamycin Doxycycline Metronidazole
0.008-16 0.008-1.0 0.125-16.0 0.016-0.5 0.064-0.5 0.016-0.5 0.008-32 0.008-2.0 0.016-32 0.032-2.0 0.032-8.0 0.016-0.5 0.032-16 0.008-1.0 0.016-32 0.016-0.25 0.016-0.25 0.125-8.0 0.25-4.0
1.0 0.25 8.0 0.125 0.064 0.125 4.0 1.0 4.0 0.5 1.0 0.25 4.0 0.125 4.0 0.125 0.064 0.25 0.5
8.0 0.5 16.0 0.25 0.25 0.25 8.0 2.0 16 0.2 4.0 1.0 8.0 0.25 16 0.125 0.125 4.0 2.0
BAY v 3522 (+) BAY v 3522 (-) Amoxicillin (+) Amoxicillin (-)
0.008-16 0.008-0.25 0.016-16 0.008-0.25 0.032-1.0 0.008-0.25 0.016-64 0.016-2.0 0.032-32 0.016-4.0 0.008-2.0 0.008-0.25 0.016-32 0.016-0.5 0.064-32 0.032-1.0 0.25-2.0 0.25-4.0 0.25-1.0
2.0 0.032 8.0 0.064 0.064 0.032 4.0 0.5 2.0 0.5 0.25 0.125 2.0 0.125 4.0 0.25 1.0 2.0 0.5
8.0 0.125 16 0.125 0.125 0.125 8.0 1.0 16 2.0 0.5 0.25 8.0 0.25 16 0.5 2.0 4.0 1.0
0.008-0.5 0.008-0.125 0.008-0.25 0.008-64 0.008-64 0.008-0.5 0.008-0.5 0.008-128
0.032 0.032 0.032 0.5 0.5 0.5 0.125
Cefuroxime (-) Cephalexin (+) Cephalexin (-)
Clindamycin Doxycycline Metronidazole
Bacteroides intermedius (10 ,-1actamase-negative strains)
BAY v 3522 Amoxicillin Amoxicillin-clavulanate Cefaclor Cefadroxil Cefoxitin Cefuroxime
Cephalexin Clindamycin Doxycycline Bacteroides melaninogenicus (5 3-1actamase-positive and 5 ,-l1actamase-negative strains)
Bacteroides ruminicola (5 P-1actamase-positive and 5 ,-1actamase-negative strains)
Amoxicillin-clavulanate (+) Amoxicillin-clavulanate (-) Cefaclor (+) Cefaclor (-) Cefadroxil (+) Cefadroxil (-) Cefoxitin (+) Cefoxitin (-) Cefuroxime (+) Cefuroxime (-) Cephalexin (+) Cephalexin (-)
Clindamycin Doxycycline Metronidazole Fusobacterium species (40)'
MIC (mg/liter)a Range
BAY v 3522 Amoxicillin
Amoxicillin-clavulanate Cefaclor
Cefadroxil Cefoxitin Cefuroxime Cephalexin
0.5
0.064 4.0 2.0
%
Resistantb
0 10 0
0 0 0 0 0 0
0 0 0 0
0 0
0 0 0
0 0 0 0
0 0
0 0 0
0.5
0.125 0.25 64 64 0.5 0.5 128
0 0 0
Continued on following page
599
NOTES
VOL. 35, 1991
TABLE 1-Continued Microorganism (no. of isolates)
. g. tMIC Antmcrobal agent Range
Clindamycin Doxycycline Metronidazole
0.016 0.008-0.125 0.25-4.0
(mg/liter)a 50%
90%
% Resistantb
0.016 0.032 4.0
0.016 0.125 4.0
0 0 0
50% and 90%, MICs for 50 and 90% of strains tested, respectively. Strains were classified as resistant when the MIC was greater than the break-point concentration. c Includes Peptostreptococcus anaerobius (n = 4), Peptostreptococcus asaccharolyticus (n = 6), Peptostreptococcus indolicus (n = 3), Peptostreptococcus magnus (n = 6), Peptostreptococcus micros (n = 10), Peptostreptococcus prevotii (n = 7), Streptococcus intermedius (n = 12), and Streptococcus morbillorum (n = 2). d +, f3-Lactamase-positive strains; -, P-lactamase negative strains. eIncludes Fusobacterium nucleatum (n = 35), Fusobacterium mortiferum (n = 2), and Fusobacterium varium (n = 3). a
b
(MIC, >16 mg/liter). All isolates were susceptible to clindamycin, while 10% of the B. asaccharolyticus strains, 10% of the B. bivius strains, and 10% of the B. disiens strains were resistant to doxycycline (MIC, >8 mg/liter). One B. asaccharolyticus isolate was found to be resistant to metronidazole (MIC, >16 mg/liter). All fusobacteria were susceptible to BAY v 3522, amoxicillin, amoxicillin-clavulanate, cefoxitin, and cefuroxime, while the MICs of cefaclor, cefadroxil, and cephalexin for 90% of strains tested were high (64 to 128 mg/liter). For most isolates, MICs of clindamycin, doxycycline, and metronidazole were low. In summary, the new peroral cephalosporin BAY v 3522 demonstrated good in vitro activity against anaerobic bacte-
ria except for f-lactamase-producing Bacteroides strains. BAY v 3522 has an antibacterial activity that warrants further clinical investigations. REFERENCES 1. Dornbusch, K., C. E. Nord, and B. Olsson-Liljequist. 1979. Antibiotic susceptibility of anaerobic bacteria with special reference to Bacteroides fragilis. Scand. J. Infect. Dis. 19:17-25. 2. Holdeman, L. V., E. P. Cato, and W. E. C. Moore (ed.). 1977. Anaerobe laboratory manual, 4th ed. Virginia Polytechnic Institute and State University, Blacksburg. 3. National Committee for Clinical Laboratory Standards. 1989. M11-T2. Tentative standard. National Committee for Clinical Standards, Villanova, Pa.
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, Mar. 1991, p. 594-599 0066-4804/91/030594-06$02.00/0 Copyright C) 1991, American Society for Microbiology
Susceptibility of Anaerobic Bacteria to BAY
v
3522
CARL ERIK NORD,'* MARGARETA RYLANDER,2 AND S. RAGNAR NORRBY3 Department of Microbiology, Huddinge University Hospital,' and Department of Clinical Microbiology, Karolinska Hospital,2 Karolinska Institute, Stockholm, and Department of Infectious Diseases, Lund University Hospital, University of Lund, Lund,3 Sweden Received 31 August 1990/Accepted 17 December 1990
The activity of BAY v 3522 against 340 strains of anaerobic bacteria was determined by an agar dilution method. Its activity was compared with those of amoxicillin, amoxicillin-clavulanate, cefaclor, cefadroxil, cefoxitin, cefuroxime, cephalexin, clindamycin, doxycycline, and metronidazole. BAY v 3522, amoxicillinclavulanate, cefoxitin, clindamycin, and metronidazole were the most active agents tested. On the basis of these results, BAY v 3522 appears to have an antibacterial activity that warrants further investigation in clinical trials.
BAY v 3522 is a new oral cephalosporin which has the following formula: 7-[D-2-amino-2-(2-aminobenzothiazol-6yl)-acetamido]-3-[(Z)-1-propen-1-yl]-3-cephem-4-carboxylic acid monohydrate. It is produced by Bayer AG, Wuppertal, Federal Republic of Germany. The purpose of the present investigation was to determine the in vitro activity of BAY v 3522 against anaerobic bacteria recently isolated from respiratory tract and wound infections. Its activity was compared with those of amoxicillin, amoxicillin-clavulanate, cefaclor, cefadroxil, cefoxitin, cefuroxime, cephalexin, clindamycin, doxycycline, and metronidazole. All strains were identified by the criteria of Holdeman et al. (2). The antimicrobial susceptibility tests were performed by the method of Dornbusch et al. (1). The strains were grown in rubber-stoppered tubes containing prereduced chopped meat broth with glucose. Antimicrobial susceptibility testing was performed on PDM-ASM agar (AB Biodisk, Solna, Sweden), with the addition of 5% defibrinated horse blood, by the agar dilution method. Inocula were 48-h cultures diluted 10-2 in prereduced Proteose Peptone broth (Difco Laboratories, Detroit, Mich.). This dilution resulted in 105 CFU per spot, when the bacteria were applied with a modified Steers replicator to freshly prepared agar plates containing the appropriate antimicrobial agent. An agar plate without an antimicrobial agent was always included as a growth control. The colony counts were checked after each inoculation. The plates were read after 48 h of incubation at 37°C in anaerobic jars (GasPak; BBL Microbiology Systems, Cockeysville, Md.). The MIC was defined as the lowest concentration of the drug that inhibited growth. The appearance of a single colony or of a barely visible haze was disregarded. The presence of ,B-lactamase was determined by the nitrocefin disk assay. The break points, in milligrams per liter, for the following antimicrobial agents were used, as recommended by the National Committee for Clinical Laboratory Standards (3): amoxicillin-clavulanate, 16/8; cefoxitin, 16; clindamycin, 2; tetracycline, 8; and metronidazole, 16. Three control microorganisms were used for monitoring the susceptibility tests: Bacteroidesfragilis ATCC 25285, Bacteroides thetaiotaomicron ATCC 29741, and Clostridium perfringens ATCC
their respective manufacturers: amoxicillin and clavulanate, Astra Clinical Research Centre (Sodertalje, Sweden); cefaclor, Eli Lilly & Co. (Indianapolis, Ind.); cefadroxil, Bristol-Myers Int. (New York, N.Y.); cefoxitin, Merck Sharp & Dohme (Rahway, N.J.); cefuroxime and cephalexin, Glaxo (Greenford, United Kingdom); clindamycin, The Upjohn Co. (Kalamazoo, Mich.); doxycycline, Pfizer Inc. (New York, N.Y.); and metronidazole, Rhone-Poulenc Sante (Paris, France). The in vitro activities of BAY v 3522 and the other antimicrobial agents against the anaerobic bacteria tested are given in Table 1. All anaerobic cocci were highly susceptible to BAY v 3522, amoxicillin, amoxicillin-clavulanate, clindamycin, doxycycline, and metronidazole, while higher MICs for cefaclor, cefadroxil, cefoxitin, cefuroxime, and cephalexin were observed. BAY v 3522, amoxicillin, amoxicillin-clavulanate, clindamycin, and doxycycline were the most active drugs against Propionibacterium acnes strains. These agents were more active against P. acnes than were cefaclor, cefadroxil, cefoxitin, cefuroxime, and cephalexin. All strains were resistant to metronidazole. Ninety percent of C. perfringens isolates were inhibited by 0.032 mg of BAY v 3522 and amoxicillin per liter; 0.064 mg of amoxicillin-clavulanate per liter; 0.125 mg of doxycycline per liter; 1.0 mg of cefoxitin, cefuroxime, clindamycin, and metronidazole per liter; 4.0 mg of cefaclor per liter; and 8.0 mg of cefadroxil and cephalexin per liter. Many ,3-lactamase-producing strains in the Bacteroides fragilis group (B. fragilis, B. uniformis, B. ovatus, B. vulgatus, B. thetaiotaomicron, and B. distasonis) were resistant to six of the beta-lactam antibiotics tested (MIC, >16 mg/liter). All strains were susceptible to the combination amoxicillin-clavulanate. Ten percent of the B. fragilis and B. uniformis strains were resistant to cefoxitin. All isolates were susceptible to metronidazole, whereas 10% of the B. fragilis strains were resistant to clindamycin and doxycycline, and 10% of the B. distasonis isolates were resistant to
doxycycline. For the strains in the non-B. fragilis group (B. asaccharolyticus, B. bivius, B. disiens, B. intermedius, B. melaninogenicus, and B. ruminicola), which were ,B-lactamase positive, MICs of the beta-lactam antibiotics tested were higher than those for the P-lactamase-negative strains, except for that of amoxicillin-clavulanate. However, only B. asaccharolyticus strains were found to be resistant to amoxicillin
13124. The following antimicrobial agents were obtained from *
Corresponding author. 594
VOL. 35, 1991
NOTES
595
TABLE 1. Comparative in vitro activities of BAY v 3522 and other antimicrobial agents against anaerobic bacteria Microorganism
(no. of isolates) Anaerobic cocci (50)c
Propionibacterium acnes (30)
Clostridium perfringens (30)
Bacteroides fragilis (61 P-lactamase-positive and 5 P-lactamase-negative strains)
Antimicrobial agent BAY v 3522 Amoxicillin Amoxicillin-clavulanate Cefaclor Cefadroxil Cefoxitin Cefuroxime Cephalexin Clindamycin Doxycycine Metronidazole
0.008-2.0 0.008-0.5 0.008-0.5 0.008-32 0.125-16 0.064-8.0 0.064-8.0 0.008-32 0.016-1.0 0.032-1.0 0.125-8.0
BAY v 3522 Amoxicillin Amoxicillin-clavulanate Cefaclor Cefadroxil Cefoxitin Cefuroxime Cephalexin Clindamycin Doxycycline Metronidazole
SO0o
90to
0.125 0.064 0.125 1.0 1.0 1.0 0.25 1.0 0.064 0.125 4.0
1.0 0.25 0.25 4.0 4.0 4.0 4.0 4.0 0.064 0.5 4.0
0.008-0.5 0.016-0.125 0.125-0.25 0.008-4.0 0.008-1.0 0.032-1.0 0.032-0.5 0.008-2.0 0.016-0.064 0.125 32->64
0.064 0.064 0.064 1.0 0.5 0.125 0.125 1.0 0.016 0.125 >64
0.25 0.125 0.125 2.0 0.5 0.25 0.25 1.0 0.032 0.125 >64
BAY v 3522 Amoxicillin Amoxicillin-clavulanate Cefaclor Cefadroxil Cefoxitin Cefuroxime Cephalexin Clindamycin Doxycycline Metronidazole
0.008-0.032 0.008-0.064 0.008-0.064 0.008-4.0 0.125-8.0 0.064-1.0 0.064-2.0 0.25-16 0.008-1.0 0.008-16 1.0-4.0
0.016 0.008 0.008 0.5 0.5 0.5 0.125 1.0 0.125 0.064 1.0
0.032 0.032 0.064 4.0 8.0 1.0 1.0 8.0 1.0 0.125 1.0
BAY v 3522 (+)d BAY v 3522 (-)d Amoxicillin (+) Amoxicillin (-)
2.0->16 16 8.0->16 16 0.25-4.0 0.25-1.0 1.0->128 64 ->128 2.0->128 8.0-128 1.0-32 1.0-16 4.0->16 16->16 4.0->128 16-128 0.016-2.0 0.25->8.0 0.25-2.0
Amoxicillin-clavulanate (+) Amoxicillin-clavulanate (-) Cefaclor (+) Cefaclor (-) Cefadroxil (+) Cefadroxil (-) Cefoxitin (+) Cefoxitin (-) Cefuroxime (+) Cefuroxime (-) Cephalexin (+) Cephalexin (-) Clindamycin Doxycycline Metronidazole Bacteroides uniformis (5 ,B-lactamase-positive and 3 P-lactamase-negative strains)
MIC (mg/liter)a
Range
BAY v 3522 (+) BAY v 3522 (-) Amoxicillin (+) Amoxicillin (-)
Amoxicillin-clavulanate (+) Amoxicillin-clavulanate (-) Cefaclor (+) Cefaclor (-) Cefadroxil (+) Cefadroxil (-) Cefoxitin (+)
16 16 16 16 0.5 0.5 64 128 16 16 8.0 8.0 16 >16 16 16 0.5 0.5 0.5
>16 16 >16 16 1.0 1.0 >128 >128 128 128 16 16 >16 >16 32 128 2.0 >8.0 1.0
4.0 4.0-16 8.0 0.25-4.0 0.5 4.0-64 32-64 8.0
16 4.0 8.0 8.0 0.5 0.5 32 64 8.0
8.0-16 1.0-32
8.0 8.0
>16 4.0 16 8.0 4.0 0.5 64 64 8.0 16 16
4.0-16
%
Resistantb 0 0 0 0 0 00 0 0
0 0 100 0 0
0 0 10 0
90 0 0 0
10 0
,10 10 0
0 0 0 0
10
Continued on following page
596
ANTIMICROB. AGENTS CHEMOTHER.
NOTES TABLE 1-Continued
Microorganism (no. of isolates)
MIC
Antimicrobial agent Cefoxitin (-) Cefuroxime (+)
Cefuroxime (-) Cephalexin (+) Cephalexin (-) Clindamycin Doxycycline Metronidazole Bacteroides ovatus (7 P-lactamase-positive strains and 1 P-lactamase-negative strain)
BAY v 3522 (+) BAY v 3522 (-) Amoxicillin (+) Amoxicillin (-) Amoxicillin-clavulanate (+) Amoxicillin-clavulanate (-) Cefaclor (+) Cefaclor (-) Cefadroxil (+) Cefadroxil (-) Cefoxitin (+) Cefoxitin (-) Cefuroxime (+) Cefuroxime (-) Cephalexin (+) Cephalexin (-) Clindamycin
Doxycycline Metronidazole Bacteroides vulgatus (2 P-lactamase-positive strains and 1
,-lactamase-negative strain)
BAY v 3522 (+) BAY v 3522 (-) Amoxicillin (+) Amoxicillin (-)
Amoxicillin-clavulanate (+) Amoxicillin-clavulanate (-) Cefaclor (+) Cefaclor (-) Cefadroxil (+) Cefadroxil (-) Cefoxitin (+) Cefoxitin (-) Cefuroxime (+) Cefuroxime (-) Cephalexin (+) Cephalexin (-)
Clindamycin Doxycycline Metronidazole Bacteroides thetaiotaomicron
(7 ,B-lactamase-positive strains)
BAY v 3522 Amoxicillin Amoxicillin-clavulanate Cefaclor Cefadroxil Cefoxitin Cefuroxime
Cephalexin Clindamycin Doxycycline Metronidazole Bacteroides distasonis (7 13-lactamase-positive strains and 1 ,-lactamase-negative strain)
(mg/liter)a
%
9%%
Range 1.0-16 2.0->16 2.0-4.0 8.0-16 16-32 0.032-1.0 0.25-8.0 0.5
50%
2.0->16 16 8.0-16 16 0.5-1.0 0.5 1.0-128 >128 4.0-128 16 1.0-16 16 1.0->16 8.0 1.0-128 16 0.125-2.0 0.25-2.0 0.5-2.0
16 16 16 16 0.5 0.5 128 >128 16 16 8.0 16 >16 8.0 16 16 1.0 0.25 1.0
>16 16 >16 16 1.0 0.5 >128 >128 128 16 16 16 >16 8.0 128 16 2.0 2.0 2.0
>16 2.0 16 2.0 0.5 0.5 8.0-128 >128 1.0-16 64 1.0-8.0 8.0 16->16 16 8.0-32 16 0.5-1.0 0.5-2.0 0.5-1.0
>16 2.0 16 2.0 0.5 0.5 8.0 >128 1.0 64 8.0 8.0 16 16 8.0 16 0.5 2.0 1.0
>16 2.0 16 2.0 0.5 0.5 128 >128 16 64 8.0 8.0 >16 16 32 16 1.0 2.0 1.0
>16 16 1.0 >128 16 8.0 >16 16 1.0 2.0 0.5
>16 >16 1.0 >128 >128 16 >16 >128 2.0 4.0 1.0
>16 8.0->16 0.5-1.0 1.0->128 16->128 1.0-16 >16 1.0->128 0.25-2.0 0.25-4.0 0.5-1.0
BAY v 3522 (+) BAY v 3522 (-) Amoxicillin (+) Amoxicillin (-)
8.0->16 8.0 8.0->16 8.0
Amoxicillin-clavulanate (+) Amoxicillin-clavulanate (-)
0.5-1.0 0.25
8.0 8.0 2.0 8.0 16 0.125 0.5 0.5
>16 8.0 16 8.0 1.0 0.25
16 >16 4.0 16 32 1.0 8.0 0.5
>16 8.0 >16 8.0 1.0 0.25
Resistantb eitn 0
0 0 0
10 0 0 0
0 0
0 0 0
0 0 0 0
0 0
0 0 100
10 0 0 0 0
10 0 0 0
Continued on following page
VOL. 35, 1991
NOTES
597
TABLE 1-Continued Microorganism (no. of isolates)
Bacteroides asaccharolyticus (5 P-lactamase-positive and 5
1-lactamase-negative strains)
Bacteroides bivius (15 ,B-lactamase-positive and 10 1-lactamase negative strains)
MIC (mg/liter)a
Antimicrobial agent
Range
90Po
>128 64 16 8.0 8.0 8.0 >16 16 16 16 0.5 0.5 0.5
>128 64 >128 8.0 8.0 8.0 >16 16 >128 16 2.0 >8.0 1.0
Cefaclor (+) Cefaclor (-) Cefadroxil (+) Cefadroxil (-) Cefoxitin (+) Cefoxitin (-) Cefuroxime (+) Cefuroxime (-) Cephalexin (+) Cephalexin (-) Clindamycin Doxycycline Metronidazole
2.0->128 64 16->128 8.0 1.0-16 8.0 16 ->16 16 8.0->128 16 0.032-2.0 0.25->8.0 0.25-1.0
BAY v 3522 (+) BAY v 3522 (-) Amoxicillin (+) Amoxicillin (-) Amoxicillin-clavulanate (+) Amoxicillin-clavulanate (-) Cefaclor (+) Cefaclor (-) Cefadroxil (+) Cefadroxil (-) Cefoxitin (+) Cefoxitin (-) Cefuroxime (+) Cefuroxime (-) Cephalexin (+) Cephalexin (-)
0.008->16 0.008-1.0 0.032->16 0.032-0.5 0.032-2.0 0.032-1.0 0.008->128 0.008-4.0 0.125-64 0.125-8.0 0.064-1.0 0.064-0.5 0.064->16 0.064-4.0 0.125-64 0.125-4.0 0.016-0.25 0.032->16 0.064->64
1.0 0.25 0.5 0.125 0.25 0.25 1.0 0.5 0.5 0.25 0.5 0.125 2.0 0.125 1.0 0.25 0.016 0.125 1.0
8.0 1.0 4.0 0.25 2.0 1.0 4.0 1.0 32 0.5 1.0 0.5 8.0 1.0 64 1.0 0.016 16 1.0
0.008->16 0.008-0.25 0.5-16 0.016-0.25 0.125-2.0 0.032-0.5 0.008-64 0.016-4.0 0.016-64 0.032-8.0 0.064-4.0 0.016-1.0 0.032-16 0.016-2.0 0.032-64 0.008-4.0 0.008-0.25 0.125-16 0.064-4.0
2.0 0.125 8.0 0.125 0.25 0.25 2.0 0.5 1.0 0.5 1.0 0.125 1.0 0.125 1.0 0.125 0.016 0.125 1.0
16 0.25 16 0.25 1.0 0.5 8.0 2.0 32 1.0 4.0 0.25 8.0 1.0 32 2.0 0.032 16 2.0
0.016-16 0.016-0.5 0.032-32 0.016-0.5 0.016-2.0 0.016-0.5 0.008-64 0.008-2.0 0.032-32 0.032-4.0 0.032-4.0
1.0 0.125 8.0 0.125 0.5 0.125 4.0 1.0 2.0 0.25
4.0 0.25 16 0.25
0.016-0.5 0.016-32
0.25 2.0
Clindamycin Doxycycline Metronidazole BAY v 3522 (+) BAY v 3522 (-) Amoxicillin (+) Amoxicillin (-)
Amoxicillin-clavulanate (+) Amoxicillin-clavulanate (-) Cefaclor (+) Cefaclor (-) Cefadroxil (+) Cefadroxil (-) Cefoxitin (+) Cefoxitin (-) Cefuroxime (+) Cefuroxime (-) Cephalexin (+) Cephalexin (-) Clindamycin Doxycycline Metronidazole Bacteroides disiens (13 j-lactamase-positive and 12 P-1actamase-negative strains)
%
50to
BAY 3522 (+) BAY 3522 (-) Amoxicillin (+) v
v
Amoxicilin
(-)
Amoxicillin-clavulanate
(+)
Amoxicillin-clavulanate
(-)
Cefaclor (+) Cefaclor (-) Cefadroxil (+) Cefadroxil (-) Cefoxitin (+) Cefoxitin (-) Cefuroxime (+)
1.0
1.0
0.25 8.0 2.0 16 0.5 2.0 0.5 8.0
Resistantb
0 0
0 10 0
4 0 0 0
0 0
0 10 10
0 0 0 0
0 0
0 10 0
10 0 0 0
0 0
Continued on following page
598
NOTES
ANTIMICROB. AGENTS CHEMOTHER.
TABLE 1-Continued Microorganism (no. of isolates)
Antimicrobial agent
50%o
901J
0.008-1.0 0.125-32 0.032-2.0 0.016-0.25 0.125-16 0.125-2.0
0.25 2.0 0.25 0.032 0.2 0.5
0.5 16 0.5 0.125 16 1.0
0.064 0.016 0.016 0.5 0.25 0.125 0.25 0.5 0.032 0.5 0.5
0.5 0.125 0.125 2.0 2.0 0.25 2.0 4.0
Metronidazole
0.008-1.0 0.008-0.5 0.008-0.5 0.008-4.0 0.008-4.0 0.008-1.0 0.008-4.0 0.008-4.0 0.016-0.5 0.016-8.0 0.125-4.0
BAY v 3522 (+) BAY v 3522 (-) Amoxicillin (+) Amoxicillin (-) Amoxicillin-clavulanate (+) Amoxicillin-clavulanate (-) Cefaclor (+) Cefaclor (-) Cefadroxil (+) Cefadroxil (-) Cefoxitin (+) Cefoxitin (-) Cefuroxime (+) Cefuroxime (-) Cephalexin (+) Cephalexin (-) Clindamycin Doxycycline Metronidazole
0.008-16 0.008-1.0 0.125-16.0 0.016-0.5 0.064-0.5 0.016-0.5 0.008-32 0.008-2.0 0.016-32 0.032-2.0 0.032-8.0 0.016-0.5 0.032-16 0.008-1.0 0.016-32 0.016-0.25 0.016-0.25 0.125-8.0 0.25-4.0
1.0 0.25 8.0 0.125 0.064 0.125 4.0 1.0 4.0 0.5 1.0 0.25 4.0 0.125 4.0 0.125 0.064 0.25 0.5
8.0 0.5 16.0 0.25 0.25 0.25 8.0 2.0 16 0.2 4.0 1.0 8.0 0.25 16 0.125 0.125 4.0 2.0
BAY v 3522 (+) BAY v 3522 (-) Amoxicillin (+) Amoxicillin (-)
0.008-16 0.008-0.25 0.016-16 0.008-0.25 0.032-1.0 0.008-0.25 0.016-64 0.016-2.0 0.032-32 0.016-4.0 0.008-2.0 0.008-0.25 0.016-32 0.016-0.5 0.064-32 0.032-1.0 0.25-2.0 0.25-4.0 0.25-1.0
2.0 0.032 8.0 0.064 0.064 0.032 4.0 0.5 2.0 0.5 0.25 0.125 2.0 0.125 4.0 0.25 1.0 2.0 0.5
8.0 0.125 16 0.125 0.125 0.125 8.0 1.0 16 2.0 0.5 0.25 8.0 0.25 16 0.5 2.0 4.0 1.0
0.008-0.5 0.008-0.125 0.008-0.25 0.008-64 0.008-64 0.008-0.5 0.008-0.5 0.008-128
0.032 0.032 0.032 0.5 0.5 0.5 0.125
Cefuroxime (-) Cephalexin (+) Cephalexin (-)
Clindamycin Doxycycline Metronidazole
Bacteroides intermedius (10 ,-1actamase-negative strains)
BAY v 3522 Amoxicillin Amoxicillin-clavulanate Cefaclor Cefadroxil Cefoxitin Cefuroxime
Cephalexin Clindamycin Doxycycline Bacteroides melaninogenicus (5 3-1actamase-positive and 5 ,-l1actamase-negative strains)
Bacteroides ruminicola (5 P-1actamase-positive and 5 ,-1actamase-negative strains)
Amoxicillin-clavulanate (+) Amoxicillin-clavulanate (-) Cefaclor (+) Cefaclor (-) Cefadroxil (+) Cefadroxil (-) Cefoxitin (+) Cefoxitin (-) Cefuroxime (+) Cefuroxime (-) Cephalexin (+) Cephalexin (-)
Clindamycin Doxycycline Metronidazole Fusobacterium species (40)'
MIC (mg/liter)a Range
BAY v 3522 Amoxicillin
Amoxicillin-clavulanate Cefaclor
Cefadroxil Cefoxitin Cefuroxime Cephalexin
0.5
0.064 4.0 2.0
%
Resistantb
0 10 0
0 0 0 0 0 0
0 0 0 0
0 0
0 0 0
0 0 0 0
0 0
0 0 0
0.5
0.125 0.25 64 64 0.5 0.5 128
0 0 0
Continued on following page
599
NOTES
VOL. 35, 1991
TABLE 1-Continued Microorganism (no. of isolates)
. g. tMIC Antmcrobal agent Range
Clindamycin Doxycycline Metronidazole
0.016 0.008-0.125 0.25-4.0
(mg/liter)a 50%
90%
% Resistantb
0.016 0.032 4.0
0.016 0.125 4.0
0 0 0
50% and 90%, MICs for 50 and 90% of strains tested, respectively. Strains were classified as resistant when the MIC was greater than the break-point concentration. c Includes Peptostreptococcus anaerobius (n = 4), Peptostreptococcus asaccharolyticus (n = 6), Peptostreptococcus indolicus (n = 3), Peptostreptococcus magnus (n = 6), Peptostreptococcus micros (n = 10), Peptostreptococcus prevotii (n = 7), Streptococcus intermedius (n = 12), and Streptococcus morbillorum (n = 2). d +, f3-Lactamase-positive strains; -, P-lactamase negative strains. eIncludes Fusobacterium nucleatum (n = 35), Fusobacterium mortiferum (n = 2), and Fusobacterium varium (n = 3). a
b
(MIC, >16 mg/liter). All isolates were susceptible to clindamycin, while 10% of the B. asaccharolyticus strains, 10% of the B. bivius strains, and 10% of the B. disiens strains were resistant to doxycycline (MIC, >8 mg/liter). One B. asaccharolyticus isolate was found to be resistant to metronidazole (MIC, >16 mg/liter). All fusobacteria were susceptible to BAY v 3522, amoxicillin, amoxicillin-clavulanate, cefoxitin, and cefuroxime, while the MICs of cefaclor, cefadroxil, and cephalexin for 90% of strains tested were high (64 to 128 mg/liter). For most isolates, MICs of clindamycin, doxycycline, and metronidazole were low. In summary, the new peroral cephalosporin BAY v 3522 demonstrated good in vitro activity against anaerobic bacte-
ria except for f-lactamase-producing Bacteroides strains. BAY v 3522 has an antibacterial activity that warrants further clinical investigations. REFERENCES 1. Dornbusch, K., C. E. Nord, and B. Olsson-Liljequist. 1979. Antibiotic susceptibility of anaerobic bacteria with special reference to Bacteroides fragilis. Scand. J. Infect. Dis. 19:17-25. 2. Holdeman, L. V., E. P. Cato, and W. E. C. Moore (ed.). 1977. Anaerobe laboratory manual, 4th ed. Virginia Polytechnic Institute and State University, Blacksburg. 3. National Committee for Clinical Laboratory Standards. 1989. M11-T2. Tentative standard. National Committee for Clinical Standards, Villanova, Pa.
