646
Comparative in Vitro Activity of Cefdinir (CI-983; FK-482) against Staphylococci, Gram-Negative Bacilli and Respiratory Tract Pathogens S.R. Scriver, B.M. Willey, D.E. Low, A.E. Simor*
The in vitro activity of cefdinir (CI-983; FK-482), a new oral cephalosporin, was compared with that of other antimicrobial agents against clinical isolates of staphylococci, gram-negative bacilli and common respiratory tract pathogens. Cefdinir (MIC90 _ ~14 ~g/ml) and equally as active as cefuroxime (MIC90 2.0 ~g/ml) against oxacillin-susceptible staphylococci. Cefdinir was active againstHaemophilus influenzae, including 15-1actamase producers (MIC90 0.5/ag/ml), Moraxella catarrhalis (MIC90 _ 64 lag/ml).
Vol. 11, 1992
647
Table la C o m p a r a t i v e i n v i t r o activity of cefdinir (CI-983; FK-482) and o t h e r antimicrobial agents against staphylococci. Organism (n)
Antimicrobial agent
M I C (~g/ml) MIC50
Staphylococcus aureus
MICg0
Range
Cefdinir Oxacillin Cefazolil Cefuroxime Cefixime Ceftibuten Cefamandole Cefpirome
0.5 0.25 0.5 2,0 >64.0 >~.0 0.5 1.0
1.0 0.5 1.0 2.0 >64.0 >64.0 1.0 2.0
50.~ -8.0 N0.06-2.0 0.25-2.0 0.5-16.0 8.0->64.0 32.0->64.0 0.12-4.0 0.5-4.0
Cefdinir Oxaeillin Cefazolin Cefuroxime Cefixime Ceftibuten Cefamandole Cefpirome
32.0 64.0 16.0 32.0 > 64.0 > 64.0 8.0 8.0
> > > > > >
64.0 64.0 64.0 64.0 64.0 64.0 32.0 64.0
1.0 8.0 1.0 2.0 64.0 > 64.0 1.01.0-
64.0 64.0
Staphylococcus haemolyticus (165)
Cefdinir Oxacillin Cefazolin Cefuromme Cefixime Ceftibuten Cefamandote Cefpirome
> 64.0 > 64.0 > 64.0 > 64.0 > 64.0 > 64.0 16.0 32.0
> 64.0 > 64.0 > 64,0 > 64.0 > 64,0 > 64.0 32.0 64.0
0.5 < 0.06 0.5 2.0 8.0 16.0 0.5 0.5-
> 64.0 > 64.0 > 64,0 > 64.0 > 64,0 > 64,0 > 64.0 64.0
Staphylococcus saprophyticus
Cefdinir Oxacillin Cefazolin Cefuroxime Cefixime Ccftibuten Cefamandole Cefpirome
1,0 0.50 2.0 4.0 > 64,0 > 64.0 1,0 1.0
2.0 0.50 2.0 8,0 > 64.0 > 64.0 2.0 2.0
< 0.06 _ 32.0 > 64.0 > 64,0 > 64.0 64.0 8.0
C o a g u l a s e - n e g a t i v e staphylococci OXacillin-suseeptible (129)
Cefdinir Oxacillin Cefazolin Cefuroxime Cefixime Ceftibuten Cefamandole Cefpirome
0.25 0.25 1.0 1.0 64.0 > 64.0 1.0 0.5
1.0 2.0 2,0 2.0 > 64,0 > 64,0 2.0 2.0
< 0.06 < 0,06 0.120.258,0 4,0 _ 64.0 > 64,0 4.0 8.0
C o a g u l a s e - n e g a t i v e staphylococci OXaeillin-resistant
Cefdinir Oxacillin Cefazolin Cefuroxlme Cefixime Ceftibuten Cefamandole Cefpirome
1.0 16.0 16.0 4.0 > 64,0 > 64.0 4,0
> > > > > > >
Oxacillin-susceptible
(161)
Staphylococcus aureus oxaeillin-resistant (161)
06o)
(22)
Table 2 summarizes the activity of cefdinir and Other antimicrobials against a variety of gramnegative bacilli. Like most of the other cephalo-
8.0
64.0 64,0 64.0 64.0 64.0 64.0 64.0
64.0
0,25 4.0 2.0 1.0 64 64 2.0
-
> > > > >
> > > > > > >
64,0 64.0 64.0 64.0 64.0
64.0 64.0 64.0 64.0 64.0 64,0 64.0
4 . 0 - 64.0
sporins tested, cefdinir was found to have good in vitro activity against Escherichia coli, Klebsiella pneurnoniae, Proteus mirabilis and Providencia
648
E u r . J. C l i n . M i c r o b i o l .
Infect. Dis.
T a b l e 2: C o m p a r a t i v e in vitro activity o f cefdinir (CI-983; F K - 4 8 2 ) a n d o t h e r a n t i m i c r o b i a l a g e n t s a g a i n s t g r a m - n e g a t i v e bacteria. Organism (n)
Escherichia coli (88)
Antimicrobial agent MIC50
MIC90
Ceftibuten Cefamandole Cefoxitin Cefotaxime Ceftizoxime Ceftazidime Cefpirome Ampicillin
0.25 4.0 1.0 2.0 1.0 4.0 - 32.0
~ 0.06 1.00.12 0.25'; 0.06 1.0 < 0.06 < 0.06 _ 64.0 64.0 > 64.0 > 64.0 > 64.0 > 64.0 > 64.0 > 64.0 > 64.0 4.0 > 32.0
0.25 0.500.25 0.25 _ 64.0 > 64,0 > 64.0 > 64,0 > 64.0 > 64.0 > 64.0 > 64.0 > 32.0
Cefdinir Cefuroxime
Cefixime
Klebsiella pneumoniae (83)
Serratia marcescens
(85)
Cefoxitin Cefotaxime Ceftizoxime Ceftazidime Cefpirome Ampicillin
Enterobacter spp.
(85)
M I C (lag/ml)
Cefdinir Cefuroxime Cefixime Ceftibuten Cefamandole Cefoxitin Cefotaxime Ceftizoxime Ceftazidime Cefpirome Ampicillin
16.0 > 64.0 1.0 1.0 0.5 0.12 > 32.0
Range 4,0 16.0 8,0 16.0 64.0 > 64.0 0.25 0.5 8.0 0.5 > 32
1 . 0 - 16.0
Vol. 11, 1992
649
Table 2 continued Organism (n)
Antimicrobial agent
M I C (gg/ml) MIC50
MIC90
Cefdinir Cefuroxime Cefixime Ceftibuten Cefamandole Cefoxitin Cefotaxime Ceftizoxime Ceftazidime Cefpirome Ampicillin
0.12 1.0 1.0 0.25 1.0 2.0 _ 64.0 > 64.0 32.0 64.0 4,0 8.0 > 32,0
> 64.0 > 64.0 > 64.0 > 64.0 > 64.0 > 64.0 > 64.0 > 64.0 32.0 > 64.0 > 32.0
> 64,0 > 64.0 8.0 > 64.0 > 64.0 > 64.0 16.0 32.0 0.5 1.0 > 32.0
Proteusmirabilis (49)
(13)
Ps'eudomonas aeruginosa (74)
s p e c i e s . M o s t Morganetla morganii, Enterobacter S p e c i e s a n d Pseudomonas aeruginosa i s o l a t e s Were resistant. The activity of cefdinir and other IMactam antib i o t i c s a g a i n s t r e s p i r a t o r y t r a c t p a t h o g e n s is s u m m a r i z e d i n T a b l e 3. C e f d i n i r w a s t h e m o s t a c t i v e cephalosporin t e s t e d a g a i n s t Moraxella catarrhalis ( M I C g 0 < 0 . 1 2 ~ag/ml) a n d a l s o h a d e x c e l -
Range 8.0 16.0 2.0 0.5 16.0 16.0 0.12
- > 64.0
-
> 64.0 > 64.0 > 64.0 > 64.0
l e n t a c t i v i t y a g a i n s t Streptococcus pyogenes ( M I C 9 0 < 0 . 0 6 / a g / m I ) a n d Streptococcus pneumoniae ( M I C 9 0 < 0 . 0 6 / a g / m l ) , i n c l u d i n g i s o l a t e s with reduced susceptibility to penicillin. Cefdinir was less active than cefixime and ceftibuten but more active than the remaining cephalosporins t e s t e d a g a i n s t Haemophilus influenzae ( M I C 9 0 0.5 ~ g / m O .
650
E u r . J. C l i n . M i c r o b i o l ,
Infect. Dis.
T a b l e 3: C o m p a r a t i v e in vitro activity o f cefdinir (CI-983; F K - 4 8 2 ) a n d o t h e r a n t i m i c r o b i a l a g e n t s a g a i n s t r e s p i r a t o r y tract pathogens. i,,w,l,,,,,,
Organism (n)
Haemophilus influenzae 15-1actamase n e g a t i v e (86)
Haemophilus h,fluenzae ~-lactamase positive (92)
Streptococcus pneumoniae (178)
Streptococcus pneumoniae r e d u c e d s u s c e p t i b i l i t y to penicillin
(8)
MoraxeUa catarrhalis [~-lactamase n e g a t i v e (34)
Moraxella catarrhalis 15-1actamase positive (106)
Antimicrobial agent
M I C (lag/ml) MIC50
MIC90
Range
Cefdinir Cefaclor Cefamandole Cefuroxime Cefixime Ceftibuten Loracarbef Ampicillin Amoxieillin/CA
0.25 2.0 0.50 0.50 < 0.06 _
Comparative in Vitro Activity of Cefdinir (CI-983; FK-482) against Staphylococci, Gram-Negative Bacilli and Respiratory Tract Pathogens S.R. Scriver, B.M. Willey, D.E. Low, A.E. Simor*
The in vitro activity of cefdinir (CI-983; FK-482), a new oral cephalosporin, was compared with that of other antimicrobial agents against clinical isolates of staphylococci, gram-negative bacilli and common respiratory tract pathogens. Cefdinir (MIC90 _ ~14 ~g/ml) and equally as active as cefuroxime (MIC90 2.0 ~g/ml) against oxacillin-susceptible staphylococci. Cefdinir was active againstHaemophilus influenzae, including 15-1actamase producers (MIC90 0.5/ag/ml), Moraxella catarrhalis (MIC90 _ 64 lag/ml).
Vol. 11, 1992
647
Table la C o m p a r a t i v e i n v i t r o activity of cefdinir (CI-983; FK-482) and o t h e r antimicrobial agents against staphylococci. Organism (n)
Antimicrobial agent
M I C (~g/ml) MIC50
Staphylococcus aureus
MICg0
Range
Cefdinir Oxacillin Cefazolil Cefuroxime Cefixime Ceftibuten Cefamandole Cefpirome
0.5 0.25 0.5 2,0 >64.0 >~.0 0.5 1.0
1.0 0.5 1.0 2.0 >64.0 >64.0 1.0 2.0
50.~ -8.0 N0.06-2.0 0.25-2.0 0.5-16.0 8.0->64.0 32.0->64.0 0.12-4.0 0.5-4.0
Cefdinir Oxaeillin Cefazolin Cefuroxime Cefixime Ceftibuten Cefamandole Cefpirome
32.0 64.0 16.0 32.0 > 64.0 > 64.0 8.0 8.0
> > > > > >
64.0 64.0 64.0 64.0 64.0 64.0 32.0 64.0
1.0 8.0 1.0 2.0 64.0 > 64.0 1.01.0-
64.0 64.0
Staphylococcus haemolyticus (165)
Cefdinir Oxacillin Cefazolin Cefuromme Cefixime Ceftibuten Cefamandote Cefpirome
> 64.0 > 64.0 > 64.0 > 64.0 > 64.0 > 64.0 16.0 32.0
> 64.0 > 64.0 > 64,0 > 64.0 > 64,0 > 64.0 32.0 64.0
0.5 < 0.06 0.5 2.0 8.0 16.0 0.5 0.5-
> 64.0 > 64.0 > 64,0 > 64.0 > 64,0 > 64,0 > 64.0 64.0
Staphylococcus saprophyticus
Cefdinir Oxacillin Cefazolin Cefuroxime Cefixime Ccftibuten Cefamandole Cefpirome
1,0 0.50 2.0 4.0 > 64,0 > 64.0 1,0 1.0
2.0 0.50 2.0 8,0 > 64.0 > 64.0 2.0 2.0
< 0.06 _ 32.0 > 64.0 > 64,0 > 64.0 64.0 8.0
C o a g u l a s e - n e g a t i v e staphylococci OXacillin-suseeptible (129)
Cefdinir Oxacillin Cefazolin Cefuroxime Cefixime Ceftibuten Cefamandole Cefpirome
0.25 0.25 1.0 1.0 64.0 > 64.0 1.0 0.5
1.0 2.0 2,0 2.0 > 64,0 > 64,0 2.0 2.0
< 0.06 < 0,06 0.120.258,0 4,0 _ 64.0 > 64,0 4.0 8.0
C o a g u l a s e - n e g a t i v e staphylococci OXaeillin-resistant
Cefdinir Oxacillin Cefazolin Cefuroxlme Cefixime Ceftibuten Cefamandole Cefpirome
1.0 16.0 16.0 4.0 > 64,0 > 64.0 4,0
> > > > > > >
Oxacillin-susceptible
(161)
Staphylococcus aureus oxaeillin-resistant (161)
06o)
(22)
Table 2 summarizes the activity of cefdinir and Other antimicrobials against a variety of gramnegative bacilli. Like most of the other cephalo-
8.0
64.0 64,0 64.0 64.0 64.0 64.0 64.0
64.0
0,25 4.0 2.0 1.0 64 64 2.0
-
> > > > >
> > > > > > >
64,0 64.0 64.0 64.0 64.0
64.0 64.0 64.0 64.0 64.0 64,0 64.0
4 . 0 - 64.0
sporins tested, cefdinir was found to have good in vitro activity against Escherichia coli, Klebsiella pneurnoniae, Proteus mirabilis and Providencia
648
E u r . J. C l i n . M i c r o b i o l .
Infect. Dis.
T a b l e 2: C o m p a r a t i v e in vitro activity o f cefdinir (CI-983; F K - 4 8 2 ) a n d o t h e r a n t i m i c r o b i a l a g e n t s a g a i n s t g r a m - n e g a t i v e bacteria. Organism (n)
Escherichia coli (88)
Antimicrobial agent MIC50
MIC90
Ceftibuten Cefamandole Cefoxitin Cefotaxime Ceftizoxime Ceftazidime Cefpirome Ampicillin
0.25 4.0 1.0 2.0 1.0 4.0 - 32.0
~ 0.06 1.00.12 0.25'; 0.06 1.0 < 0.06 < 0.06 _ 64.0 64.0 > 64.0 > 64.0 > 64.0 > 64.0 > 64.0 > 64.0 > 64.0 4.0 > 32.0
0.25 0.500.25 0.25 _ 64.0 > 64,0 > 64.0 > 64,0 > 64.0 > 64.0 > 64.0 > 64.0 > 32.0
Cefdinir Cefuroxime
Cefixime
Klebsiella pneumoniae (83)
Serratia marcescens
(85)
Cefoxitin Cefotaxime Ceftizoxime Ceftazidime Cefpirome Ampicillin
Enterobacter spp.
(85)
M I C (lag/ml)
Cefdinir Cefuroxime Cefixime Ceftibuten Cefamandole Cefoxitin Cefotaxime Ceftizoxime Ceftazidime Cefpirome Ampicillin
16.0 > 64.0 1.0 1.0 0.5 0.12 > 32.0
Range 4,0 16.0 8,0 16.0 64.0 > 64.0 0.25 0.5 8.0 0.5 > 32
1 . 0 - 16.0
Vol. 11, 1992
649
Table 2 continued Organism (n)
Antimicrobial agent
M I C (gg/ml) MIC50
MIC90
Cefdinir Cefuroxime Cefixime Ceftibuten Cefamandole Cefoxitin Cefotaxime Ceftizoxime Ceftazidime Cefpirome Ampicillin
0.12 1.0 1.0 0.25 1.0 2.0 _ 64.0 > 64.0 32.0 64.0 4,0 8.0 > 32,0
> 64.0 > 64.0 > 64.0 > 64.0 > 64.0 > 64.0 > 64.0 > 64.0 32.0 > 64.0 > 32.0
> 64,0 > 64.0 8.0 > 64.0 > 64.0 > 64.0 16.0 32.0 0.5 1.0 > 32.0
Proteusmirabilis (49)
(13)
Ps'eudomonas aeruginosa (74)
s p e c i e s . M o s t Morganetla morganii, Enterobacter S p e c i e s a n d Pseudomonas aeruginosa i s o l a t e s Were resistant. The activity of cefdinir and other IMactam antib i o t i c s a g a i n s t r e s p i r a t o r y t r a c t p a t h o g e n s is s u m m a r i z e d i n T a b l e 3. C e f d i n i r w a s t h e m o s t a c t i v e cephalosporin t e s t e d a g a i n s t Moraxella catarrhalis ( M I C g 0 < 0 . 1 2 ~ag/ml) a n d a l s o h a d e x c e l -
Range 8.0 16.0 2.0 0.5 16.0 16.0 0.12
- > 64.0
-
> 64.0 > 64.0 > 64.0 > 64.0
l e n t a c t i v i t y a g a i n s t Streptococcus pyogenes ( M I C 9 0 < 0 . 0 6 / a g / m I ) a n d Streptococcus pneumoniae ( M I C 9 0 < 0 . 0 6 / a g / m l ) , i n c l u d i n g i s o l a t e s with reduced susceptibility to penicillin. Cefdinir was less active than cefixime and ceftibuten but more active than the remaining cephalosporins t e s t e d a g a i n s t Haemophilus influenzae ( M I C 9 0 0.5 ~ g / m O .
650
E u r . J. C l i n . M i c r o b i o l ,
Infect. Dis.
T a b l e 3: C o m p a r a t i v e in vitro activity o f cefdinir (CI-983; F K - 4 8 2 ) a n d o t h e r a n t i m i c r o b i a l a g e n t s a g a i n s t r e s p i r a t o r y tract pathogens. i,,w,l,,,,,,
Organism (n)
Haemophilus influenzae 15-1actamase n e g a t i v e (86)
Haemophilus h,fluenzae ~-lactamase positive (92)
Streptococcus pneumoniae (178)
Streptococcus pneumoniae r e d u c e d s u s c e p t i b i l i t y to penicillin
(8)
MoraxeUa catarrhalis [~-lactamase n e g a t i v e (34)
Moraxella catarrhalis 15-1actamase positive (106)
Antimicrobial agent
M I C (lag/ml) MIC50
MIC90
Range
Cefdinir Cefaclor Cefamandole Cefuroxime Cefixime Ceftibuten Loracarbef Ampicillin Amoxieillin/CA
0.25 2.0 0.50 0.50 < 0.06 _
