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Antimicrobial Agents and Chemotherapy, March 1998, p. 495-501, Vol. 42, No. 3
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
In Vitro Activities of Cefminox against Anaerobic
Bacteria Compared with Those of Nine Other Compounds
Dianne B.
Hoellman,1
Sheila K.
Spangler,1
Michael R.
Jacobs,2 and
Peter C.
Appelbaum1,*
Department of Pathology (Clinical
Microbiology), Hershey Medical Center, Hershey, Pennsylvania
17033,1 and
Department of Pathology
(Clinical Microbiology), Case Western Reserve University, Cleveland,
Ohio 441062
Received 21 July 1997/Returned for modification 24 November
1997/Accepted 10 December 1997
 |
ABSTRACT |
The agar dilution MIC method was used to test the activity of
cefminox, a 
-lactamase-stable cephamycin, compared with those of
cefoxitin, cefotetan, moxalactam, ceftizoxime, cefotiam, cefamandole, cefoperazone, clindamycin, and metronidazole against 357 anaerobes. Overall, cefminox was the most active -lactam, with an MIC at which
50% of isolates are inhibited (MIC50) of 1.0 µg/ml and
an MIC90 of 16.0 µg/ml. Other -lactams were less
active, with respective MIC50s and MIC90s of
2.0 and 64.0 µg/ml for cefoxitin, 2.0 and 128.0 µg/ml for
cefotetan, 2.0 and 64.0 µg/ml for moxalactam, 4.0 and >128.0 µg/ml
for ceftizoxime, 16.0 and >128.0 µg/ml for cefotiam, 8.0 and >128.0
µg/ml for cefamandole, and 4.0 and 128.0 µg/ml for cefoperazone.
The clindamycin MIC50 and MIC90 were 0.5 and
8.0 µg/ml, respectively, and the metronidazole MIC50 and
MIC90 were 1.0 and 4.0 µg/ml, respectively. Cefminox was
especially active against Bacteroides fragilis
(MIC90, 2.0 µg/ml), Bacteroides thetaiotaomicron (MIC90, 4.0 µg/ml), fusobacteria
(MIC90, 1.0 µg/ml), peptostreptococci (MIC90,
2.0 µg/ml), and clostridia, including Clostridium
difficile (MIC90, 2.0 µg/ml). Time-kill studies
performed with six representative anaerobic species revealed that at
the MIC all compounds except ceftizoxime were bactericidal (99.9%
killing) against all strains after 48 h. At 24 h, only cefminox and cefoxitin at 4× the MIC and cefoperazone at 8× the MIC
were bactericidal against all strains. After 12 h, at the MIC all
compounds except moxalactam, ceftizoxime, cefotiam, cefamandole, clindamycin, and metronidazole gave 90% killing of all strains. After
3 h, cefminox at 2× the MIC produced the most rapid effect, with
90% killing of all strains.
| |
INTRODUCTION |
Anaerobes are established causes of
serious human infections, especially in debilitated hosts. Although
infections caused by members of the Bacteroides fragilis
group occur most commonly, infections caused by other gram-negative
anaerobic rods, as well as by gram-positive cocci and rods, are
increasingly encountered (3, 25). The susceptibility
spectrum of clinically isolated anaerobes is changing. Although
-lactamase production and the concomitant resistance to -lactams
are the rule in the B. fragilis group, both phenomena are
increasingly encountered in non-B. fragilis group
Bacteroides, Prevotella,
Porphyromonas, and Fusobacterium species.
-Lactamase production has also been described in Clostridium butyricum, Clostridium ramosum, and Clostridium
clostridioforme. Metronidazole resistance is the rule among
gram-positive, non-spore-forming rods, but it has also been reported in
peptostreptococci, non-Clostridium perfringens clostridia,
and members of the B. fragilis group. Additionally,
clindamycin resistance is not unusual among anaerobic gram-negative
rods (4-11, 13, 17, 19).
With the exception of the cephamycin group, -lactam antibiotics are
generally inactive against -lactamase-producing anaerobes (4-11). Among the cephamycins, the cefoxitin MICs for these
organisms (especially for the B. fragilis group) often
cluster around the breakpoint. Cefotetan MICs are generally 1 to 2 dilutions higher than those of cefoxitin (4-11). Cefminox
is a -lactamase-stable cephamycin; previous studies have documented
that this compound has improved activity over those of other
cephamycins against -lactamase-positive and -negative aerobes and
anaerobes (1, 12, 15, 16, 20-22, 26, 27). This study has
compared the in vitro activity of cefminox with those of cefoxitin,
cefotetan, moxalactam, ceftizoxime, cefotiam, cefamandole,
cefoperazone, clindamycin, and metronidazole against 357 clinically
isolated anaerobes. The activities of these compounds against six
selected anaerobes were also studied by the time-kill method.
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MATERIALS AND METHODS |
Bacteria.
All anaerobic strains were recent clinical
isolates (1990 to 1996) which were identified by standard procedures
(14, 25) and which were kept frozen in double-strength skim
milk (Difco Laboratories, Detroit, Mich.) at 
70°C until use. Prior
to testing, the strains were subcultured twice onto enriched sheep
blood agar plates. Throughout the study, the strains were tested for
purity by Gram staining and examining the colonial morphology. Agar
dilution MIC studies were performed with all 357 strains, and time-kill studies were performed with 6 organisms, chosen to represent a spectrum
of species encountered in clinical practice.
Antimicrobial agents.
Powders of antimicrobial agents with
known potencies were obtained as follows: cefminox, Meiji Seika Pharma,
International, Tokyo, Japan; cefoxitin, Merck & Co., Rahway, N.J.;
cefotetan, Zeneca Pharmaceuticals, Wilmington, Del.; ceftizoxime,
Fujisawa Laboratories, Deerfield Park, Ill.; cefamandole, Eli Lilly & Co., Indianapolis, Ind.; cefoperazone, Pfizer, Inc., New York, N.Y.; moxalactam, Sigma Chemical Co., St. Louis, Mo.; clindamycin, The Upjohn
Co., Kalamazoo, Mich.; and metronidazole, Searle, Inc., Skokie, Ill.
Cefotiam was a gift from Arne C. Rodloff, Institute for Medical
Microbiology, University of Leipzig, Leipzig, Germany.
Susceptibility testing.
-Lactamase testing was by the
nitrocefin disk method (Cefinase; BBL Microbiology Systems,
Cockeysville, Md.) (6). No attempt was made to differentiate
between the type and amount of -lactamase(s) produced by each
enzyme-positive strain. Agar dilution susceptibility testing of 357 strains was performed by the method recommended by the National
Committee for Clinical Laboratory Standards (NCCLS) (18)
with Wilkins-Chalgren agar (Difco Laboratories) and 5% sterile
defibrinated sheep blood for non-B. fragilis group strains and inocula of 105 CFU/spot. For the six strains tested by
the time-kill method (one strain each of B. fragilis,
Bacteroides thetaiotaomicron, Prevotella bivia,
Fusobacterium mortiferum, Peptostreptococcus anaerobius, and C. perfringens), microdilution MICs
were determined according to the recommendations of NCCLS
(18) with Anaerobe Broth (Difco Laboratories) supplemented
with 5% sterile defibrinated sheep blood for non-B.
fragilis group organisms. Trays were inoculated with
106 CFU/ml. Incubation of all plates and trays used for MIC
testing was done in an anaerobic glove box (Coy Laboratory Products,
Ann Arbor, Mich.) in an atmosphere of 85% N2, 5%
H2, and 10% CO2. Standard quality control
strains were included with each run.
Time-kill testing.
The time-kill testing methodology was
that which we have described previously (23, 24). Inocula
for time-kill studies were prepared inside the anaerobe chamber as
follows. Five colonies from plates were suspended in 4 ml of prereduced
brucella broth (Difco Laboratories), and the suspension was vortexed. A
100-µl aliquot of this suspension was added to 3.6 ml of prereduced
brucella broth and 400 µl of laked horse erythrocytes. For
metronidazole, for which thorough prereduction is necessary, 200 µl
of Oxyrase solution (Oxyrase, Inc., Mansfield, Ohio) was added. Oxyrase
is an enzyme prepared from Escherichia coli cell membranes
which, in the presence of formate, lactate, and succinate, binds
O2. The suspensions were placed into borosilicate screw-cap
tubes (15 by 45 mm) with 13-425 screw-thread, open-top screw caps and 13-mm Teflon-faced rubber septa. The tubes were removed from the chamber and were incubated for 24 h in a shaking water bath at 35°C.
After the preincubation described above, the antibiotics were prepared
to a volume of 3.6 ml as follows. Syringes containing laked horse
blood, brucella broth, and antibiotics were drawn up separately inside
the chamber and appropriate volumes were mixed in screw-cap tubes with
septa, avoiding the introduction of air. Ranges included 3 dilutions
above and 3 dilutions below the broth microdilution MICs. One
antibiotic-free growth control was used in each experiment. Aliquots
containing 200 µl of an appropriately diluted inoculum were added,
with the final inoculum being 106 to 107 CFU/ml
(23, 24). The suspensions were incubated at 35°C in a
shaking water bath, and viability counts were determined at 0, 3, 12, 24, and 48 h (23, 24). The plates were incubated inside
the chamber for 48 h; plates yielding 30 to 300 colonies were used to
determine viability counts. Each experiment was done in duplicate, and
the mean was used. The data were analyzed by expressing growth as the
log10 CFU per milliliter higher or lower than the count for
the original inoculum at 0 h. Bacteriostatic activity was defined
as 0 to 3 
log10 CFU/ml and bactericidal activity was
defined as >3 log10 CFU/ml at each of the time periods compared to the counts at 0 h.
Drug carryover was minimized as described previously (
23,
24). We believe that the spreading of 0.1 ml of undiluted broth
onto a plate containing 25 ml of medium would dilute the drug
1:250;
further 10-fold dilutions would dilute the drug 1:2,500,
1:25,000, etc.
With the concentrations of drugs used, only undiluted
inocula would
have had any potential for drug carryover, and only
plates with low
counts (<1,000 CFU/ml) would be likely to be affected.
We therefore
feel that drug carryover was not a confounding factor
in data
generation.
| |
RESULTS |
-Lactamase was detected in 91 of 99 (91.9%) of the B. fragilis group, 33 of 67 (49.3%) of the Prevotella and
Porphyromonas isolates, and 4 of 59 (6.8%) of the
fusobacteria. All gram-positive strains were -lactamase negative.
The results of agar dilution MIC testing are presented in Table
1.Overall,
cefminox was the most active -lactam, with an MIC at which 50% of
strains are inhibited (MIC50) of 1.0 µg/ml and an
MIC90 of 16.0 µg/ml. The other -lactams were less
active, with respective MIC50s and MIC90s of
2.0 and 64.0 µg/ml for cefoxitin, 2.0 and 128.0 µg/ml for
cefotetan, 2.0 and 64.0 µg/ml for moxalactam, 4.0 and >128.0 µg/ml
for ceftizoxime, 16.0 and >128.0 µg/ml for cefotiam, 8.0 and >128.0
µg/ml for cefamandole, and 4.0 and 128.0 µg/ml for cefoperazone.
The clindamycin MIC50 and MIC90 were 0.5 and
8.0 µg/ml, respectively, and the metronidazole MIC50 and
MIC90 were 1.0 and 4.0 µg/ml, respectively. Cefminox was
especially active against B. fragilis (MIC90,
2.0 µg/ml), B. thetaiotaomicron (MIC90, 4.0 µg/ml), fusobacteria (MIC90, 1.0 µg/ml),
peptostreptococci (MIC90, 2.0 µg/ml), and clostridia, including Clostridium difficile (MIC90, 2.0 µg/ml). Although cefminox was generally more active, especially
against Bacteroides species, fusobacteria, and C. difficile, this cephamycin was frequently twofold less active than
cefoxitin against Prevotella, Porphyromonas and
Peptostreptococcus spp. and had activity similar to that of cefoxitin against the other species tested.
-Lactam MICs for Bacteroides ovatus and Bacteroides
distasonis strains were uniformly high; some strains were also
resistant to clindamycin (
4.0 µg/ml). The highest -lactam MICs
for any of the members of the Prevotella and
Porphyromonas group were for Prevotella disiens.
Although -lactam MICs for all strains of Propionibacterium
acnes were 
2.0 µg/ml, for the other gram-positive, non-spore-forming rods tested, -lactam MICs were much higher.
The microdilution MIC results for the six strains used for time-kill
experiments are listed in Table 2. The
MICs were within 1 doubling dilution of those obtained by the agar
dilution method. The results of the time-kill experiments (Table
3) revealed that at and above the MIC all
compounds except ceftizoxime were bactericidal (99.9% killing) against
all strains after 48 h. At 24 h, only cefminox and cefoxitin
at 4× the MIC and cefoperazone at 8× the MIC were bactericidal
against all strains. After 12 h, at the MIC all compounds except
moxalactam, ceftizoxime, cefotiam, cefamandole, clindamycin, and
metronidazole produced 90% killing of all strains. After 3 h,
cefminox at 2× the MIC produced the most rapid effect, giving 90%
killing of all strains. The killing kinetics of all compounds at the
MIC against the B. fragilis strain (Table 2) are presented
in Fig. 1.
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FIG. 1.
Killing kinetics of a strain of B. fragilis
(Table 2) by drugs used at the MIC.  , cefminox;  , metronidazole;
 , ceftizoxime;  , clindamycin;  , cefotiam;  , cefotetan;  ,
cefoperazone;  , cefmandole; ×, cefmitin; +, moxalactam;
____, threshold; *, positive controls.
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|
| |
DISCUSSION |
Cefminox is a cephamycin antibiotic with antibacterial activity
against a variety of aerobic gram-positive and -negative bacteria. Its
activity is especially higher than those of conventional cephamycins against E. coli, Klebsiella pneumoniae,
Proteus mirabilis, Proteus vulgaris,
Serratia marcescens, Yersinia enterocolitica, and
Burkholderia cepacia. Moreover, cefminox is as stable as
most other cephamycins to the actions of the -lactamases produced by
these bacteria. Although cefminox MICs are higher than those of the
other cephamycins for some species, it displays an earlier onset of
activity and a higher rate of bactericidal activity than those
compounds. In contrast to ceftizoxime, cefminox and cefoxitin have
negligible inoculum effects against E. coli (12, 15,
22).
The results of our in vitro MIC and time-kill experiments, in which we
tested the largest number and widest spectrum of anaerobes of which we
are aware, support the results of clinical studies showing that
cefminox is clinically effective for the treatment of infections of the
respiratory, biliary, and gynecological tracts and of peritonitis
caused by gram-negative and -positive aerobes and anaerobes
(20).
Cefminox MIC and kinetic data should be considered together with
pharmacokinetic data. In human volunteers, single intravenous doses of
1 and 2 g of cefminox resulted in maximum concentrations in serum
of 56.6 ± 16.1 and 117.3 ± 7.6 µg/ml, respectively with area under the curve values of 140.9 ± 5.8 and 260.0 ± 10.4 mg · h/ml/1.73 m2, respectively (1).
Against three strains of the family Enterobacteriaceae and
one B. fragilis strain, the increase in the area under the bactericidal curve observed with the 2-g dose was at least 3.5 times
that seen with the 1-g dose and was larger than that predicted by the
corresponding increase (1.84 times) in the area under the serum
concentration-versus-time curve (AUC). The minimal bactericidal concentrations (MBCs) at 6 h showed a better association with the
bactericidal titer in serum than did standard MICs or MBCs (1). After the administration of a 1-g dose, the maximal
cefminox concentration in the pelvic retroperitoneal space was 37.9 µg/ml compared to the maximal concentrations of 30.3 µg/ml for
the other cephalosporins tested (16).
A few published studies of relatively few anaerobic strains have shown
that the MICs of cefminox for B. fragilis are lower than
those cefoxitin and cefotetan, and the cefminox MICs for peptostreptococci, C. perfringens, and C. difficile are low (15, 26). Watanabe and coworkers
(26) have confirmed our findings that the antibacterial
activity of cefminox is comparable to that of moxalactam but superior
to that of cefoxitin against B. fragilis, with the activity
of cefminox against peptostreptococci being slightly inferior to that
of cefoxitin. Cefminox was active against a wide variety of anaerobes,
excluding Clostridium innocuum (26). Soriano and
coworkers (21) have demonstrated that the susceptibility of
cefminox and cefoxitin to hydrolysis by crude extracts of
-lactamases from B. fragilis group strains does not
correlate with the results of conventional susceptibility testing. Both
compounds were found to have equivalent activities against strains that
produced enhanced levels of -lactamase. The cefminox MICs in our
study were similar to those described by previous investigators
(15, 26); however, the MIC90s for C. difficile (2.0 µg/ml) were lower than those described previously
by Inoue et al. (15) (12.5 µg/ml) but were similar to
those reported by Watanabe et al. (26) (3.13 µg/ml). In
confirmation of our findings, Watanabe and coworkers (26) have published information indicating that the cefminox MIC for B. ovatus ATCC 8483 is 6.25 µg/ml, whereas the MICs for
other members of the B. fragilis group are lower, but they
did not report the MICs for any other B. ovatus strains.
Other anaerobe species for which cefminox MICs are high (P. disiens, non-Propionibacterium acnes gram-positive,
non-spore-forming rods) either have not been studied or too few species
have been examined to permit valid comparisons (15, 26).
Because both of the studies reported above (15, 26) examined
relatively few numbers of anaerobes, valid comparisons with the results
obtained in the current study must await testing of larger numbers of
strains by other workers.
The only members of the B. fragilis group for which cefminox
MICs are high were B. ovatus and B. distasonis.
The last two species could have been strong -lactamase producers or
could have produced enzymes which differed from those produced by other gram-negative rods. This was not examined in the current study. None of
the gram-positive, non-spore-forming rods for which cefminox MIC90s were >128.0 µg/ml produced -lactamase.
The time-kill studies confirmed the activity of cefminox against
anaerobic bacteria compared to the activities of other compounds and
confirmed its higher rate of killing, especially at earlier time
periods. The results obtained for other -lactam and non--lactam compounds reflect the findings of our group and those of other investigators, i.e., higher MICs of cefotetan compared to those of
cefoxitin; the lack of activity of cefotiam, cefamandole, and cefoperazone against -lactamase-producing strains; and the good activities of clindamycin and metronidazole against all anaerobic groups except clostridia and gram-positive, non-spore-forming rods
(7-9, 15, 17, 26, 28). Of the cephalosporins tested, cefoxitin, cefotetan, and, in some cases, ceftizoxime had lower MICs
for -lactamase-positive strains compared to the MICs of the other
-lactams tested, with cefoxitin MICs being a few dilutions lower
than those of cefotetan. The higher ceftizoxime MICs compared to those
found by other investigators probably reflect the difficulty in
standardizing testing of the susceptibility of this drug against anaerobes due to trailing endpoints and a marked inoculum effect, especially in broth (2).
In summary, the results of the MIC and time-kill investigations support
previously published studies showing the clinical efficacy of cefminox.
Further studies will determine whether cefminox has a place in the
treatment of mixed infections with aerobic and anaerobic organisms.
| |
ACKNOWLEDGMENT |
This study was sponsored by Meiji Seika Kaisha, Ltd., Tokyo,
Japan.
| |
FOOTNOTES |
*
Corresponding author. Mailing address: Department of
Pathology, Hershey Medical Center, P.O. Box 850, Hershey, PA 17033. Phone: (717) 531-5113. Fax: (717) 531-7953. E-mail:
pappelba{at}psuhmc.hmc.psu.edu.
| |
REFERENCES |
| 1.
|
Aguilar, L.,
C. Esteban,
J. Frias,
I. Pérez-Balcabao,
A. J. Carcas, and R. Dal-Ré.
1994.
Cefminox: correlation between in-vitro susceptibility and pharmacokinetics and serum bactericidal activity in healthy volunteers.
J. Antimicrob. Chemother.
33:91-101[Abstract/Free Full Text].
|
| 2.
|
Aldridge, K. E.,
H. M. Wexler,
C. V. Sanders, and S. M. Finegold.
1990.
Comparison of in vitro antibiograms of Bacteroides fragilis group isolates: differences in resistance rates in two institutions because of differences in susceptibility testing methodology.
Antimicrob. Agents Chemother.
34:179-181[Abstract/Free Full Text].
|
| 3.
| Appelbaum, P. C. 1987. Anaerobic infections:
nonsporeformers, p. 45-109. In B. B. Wentworth
(coordinating ed.), Diagnostic procedures for bacterial infections.
American Public Health Association, Washington, D.C.
|
| 4.
|
Appelbaum, P. C.,
M. R. Jacobs,
S. K. Spangler, and S. Yamabe.
1986.
Comparative activity of -lactamase inhibitors YTR 830, clavulanate, and sulbactam combined with -lactams against -lactamase-producing anaerobes.
Antimicrob. Agents Chemother.
30:789-791[Abstract/Free Full Text].
|
| 5.
|
Appelbaum, P. C.,
A. Philippon,
M. R. Jacobs,
S. K. Spangler, and L. Gutmann.
1990.
Characterization of -lactamases from non-Bacteroides fragilis group Bacteroides spp. belonging to seven species and their role in -lactam resistance.
Antimicrob. Agents Chemother.
34:2169-2176[Abstract/Free Full Text].
|
| 6.
|
Appelbaum, P. C.,
S. K. Spangler, and M. R. Jacobs.
1990.
Evaluation of two methods for rapid testing for beta-lactamase production in Bacteroides and Fusobacterium.
Eur. J. Clin. Microbiol. Infect. Dis.
9:47-50[Medline].
|
| 7.
|
Appelbaum, P. C.,
S. K. Spangler, and M. R. Jacobs.
1990.
-Lactamase production and susceptibilities to amoxicillin, amoxicillin-clavulanate, ticarcillin, ticarcillin-clavulanate, cefoxitin, imipenem, and metronidazole of 320 non-Bacteroides fragilis Bacteroides and 129 fusobacteria from 28 U.S. centers.
Antimicrob. Agents Chemother.
34:1546-1550[Abstract/Free Full Text].
|
| 8.
|
Appelbaum, P. C.,
S. K. Spangler, and M. R. Jacobs.
1991.
Susceptibilities of 394 Bacteroides fragilis, non-B. fragilis group Bacteroides species, and Fusobacterium species to newer antimicrobial agents.
Antimicrobial Agents Chemother.
35:1214-1218[Abstract/Free Full Text].
|
| 9.
|
Appelbaum, P. C.,
S. K. Spangler, and M. R. Jacobs.
1993.
Susceptibility of 539 gram-positive and -negative anaerobes to new agents, including RP 59500, biapenem, trospectomycin and piperacillin/tazobactam.
J. Antimicrob. Chemother.
32:223-231[Abstract/Free Full Text].
|
| 10.
|
Appelbaum, P. C.,
S. K. Spangler,
G. A. Pankuch,
A. Philippon,
M. R. Jacobs,
R. Shiman,
E. J. C. Goldstein, and D. Citron.
1994.
Characterization of a -lactamase from Clostridium clostridioforme.
J. Antimicrob. Chemother
33:33-40[Abstract/Free Full Text].
|
| 11.
|
Appelbaum, P. C.,
S. K. Spangler,
R. Shiman, and M. R. Jacobs.
1992.
Susceptibilities of 540 anaerobic gram-negative bacilli to amoxicillin, amoxicillin-BRL 42715, amoxicillin-clavulanate, temafloxacin, and clindamycin.
Antimicrob. Agents Chemother.
36:1140-1143[Abstract/Free Full Text].
|
| 12.
|
Goi, H.,
T. Watanabe,
K. Miyauchi,
Y. Kazuno, and S. Inouye.
1985.
Comparative bactericidal and morphological effects of five cephamycins on cells of three gram-negative bacilli at decreasing drug concentrations.
Drugs Exp. Clin. Res.
11:771-780[Medline].
|
| 13.
|
Haggoud, A.,
G. V. Reysset, and M. Sebald.
1992.
Cloning of a Bacteroides fragilis chromosomal determinant coding for 5-nitroimidazole resistance.
FEMS Microbiol. Lett.
95:1-6.
|
| 14.
|
Holdeman, L. V., and W. E. C. Moore (ed.).
1977.
Anaerobic laboratory manual, 4th ed.
Virginia Polytechnic Institute and State University, Blacksburg.
|
| 15.
|
Inoue, S.,
H. Goi,
T. Watanabe,
T. Hara,
K. Miyauchi,
T. Yoshida,
Y. Kazuno,
H. Kadosawa,
F. Hirano,
K. Kawaharajo,
Y. Orikasa, and T. Nishino.
1984.
In vitro and in vivo antibacterial activities of MT-141, a new semisynthetic cephamycin, compared with those of five cephalosporins.
Antimicrob. Agents Chemother.
26:722-729[Abstract/Free Full Text].
|
| 16.
|
Ito, K.,
M. Hayasaki, and T. Tamaya.
1990.
Pharmacokinetics of cephem antibiotics in exudate of pelvic retroperitoneal space after radical hysterectomy and pelvic lymphadenectomy.
Antimicrob. Agents Chemother.
34:1160-1164[Abstract/Free Full Text].
|
| 17.
|
Jacobs, M. R.,
S. K. Spangler, and P. C. Appelbaum.
1990.
-Lactamase production, -lactam sensitivity and resistance to synergy with clavulanate of 737 Bacteroides fragilis group organisms from thirty-three US centres.
J. Antimicrob. Chemother.
26:361-370[Abstract/Free Full Text].
|
| 18.
|
National Committee for Clinical Laboratory Standards.
1993.
Methods for antimicrobial susceptibility testing of anaerobic bacteria, 3rd ed. Approved standard. NCCLS publication M11-A3.
National Committee for Clinical Laboratory Standards, Villanova, Pa.
|
| 19.
| Nord, C. E. 1986. Mechanisms of -lactam
resistance in anaerobic bacteria. Rev. Infect. Dis. 8(Suppl.
5):S543-S548.
|
| 20.
|
Omoto, S., and S. Watanabe.
1990.
Efficacy of cefminox in the treatment of bacterial infections.
Int. J. Clin. Pharm. Res.
10:361-368[Medline].
|
| 21.
|
Soriano, F.,
R. Edwards, and D. Greenwood.
1991.
Comparative susceptibility of cefminox and cefoxitin to -lactamases of Bacteroides spp.
J. Antimicrob. Chemother.
28:55-60[Abstract/Free Full Text].
|
| 22.
|
Soriano, F.,
R. Edwards, and D. Greenwood.
1991.
Effect of inoculum size on bacteriolytic activity of cefminox and four other -lactam antibiotics against Escherichia coli.
Antimicrob. Agents Chemother.
36:223-226[Abstract/Free Full Text].
|
| 23.
| Spangler, S. K., M. R. Jacobs, and P. C. Appelbaum. 1997. Time-kill study of the activity of trovafloxacin
compared with ciprofloxacin, sparfloxacin, metronidazole, cefoxitin,
piperacillin and piperacillin/tazobactam against six anaerobes. J. Antimicrob. Chemother. 39(Suppl. B):23-27.
|
| 24.
|
Spangler, S. K.,
M. R. Jacobs, and P. C. Appelbaum.
1997.
Bactericidal activity of DU-6859a compared to activities of three quinolones, three -lactams, clindamycin, and metronidazole against anaerobes as determined by time-kill methodology.
Antimicrob. Agents Chemother.
41:847-849[Abstract].
|
| 25.
|
Summanen, P.,
E. J. Baron,
D. M. Citron,
C. A. Strong,
H. M. Wexler, and S. M. Finegold.
1993.
Wadsworth anaerobic bacteriology manual, 5th ed.
Star Publishing Co., Belmont, Calif.
|
| 26.
|
Watanabe, K.,
K. Sawa,
M. Bunai, and K. Ueno.
1985.
Antibacterial activity of cefminox against anaerobes.
J. Antibiot. (Tokyo)
38:649-660[Medline].
|
| 27.
|
Watanabe, T.,
Y. Kazuno,
K. Kawaharajo,
H. Goi,
S. Inouye, and T. Nishino.
1984.
In vivo antibacterial activity of a novel cephamycin, MT-141, on gram-negative infections in mice.
Drugs Exp. Clin. Res.
10:293-302.
|
| 28.
|
Watt, B., and F. V. Brown.
1982.
In-vitro activity of cefotiam against bacteria of clinical interest.
J. Antimicrob. Chemother.
10:391-395[Abstract/Free Full Text].
|
Antimicrobial Agents and Chemotherapy, March 1998, p. 495-501, Vol. 42, No. 3
0066-4804/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.
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Abstract
Introduction
