In vitro activity of cefcanel versus other oral cephalosporins

Cefcanel is a new orally absorbed cephalosporin. Its activity was compared with that of cefuroxime, cefaclor, cephalexin, and cefixime against grampositive and negative aerobic and anaerobic bacteria. Cefcanel had excellent activity against methicillin-susceptibleStaphylococcus aureus andStaphylococcus epidermidis, MIC90 1 µg/ml, superior to the other oral cephalosporins. However, methicillin-resistant staphylococci were resistant, MIC 16 µg/ml.Streptococcus pyogenes andStreptococcus pneumoniae were inhibited by 0.015–1 µg/ml, concentrations comparable to other cephalosporins.Clostridium spp. were inhibited by 0.25 µg/ml, 8- to 128-fold lower concentrations than were found for other agents, but the MICs were >64 µg/ml forBacteroides spp. The MIC90 forMoraxella catarrhalis was 1 µg/ml, similar to cefuroxime but 16-fold greater than the MICs of cefixime.Escherichia coli andKlebsiella pneumoniae which were high beta-lactamase producers were resistant, MICs >64 µg/ml, and 50 % ofEnterobacter cloacae andCitrobacter freundii were resistant. Cefcanel was hydrolyzed by TEM-1, TEM-3 and Moraxella Bro-1 beta-lactamases.Escherichia coli containing TEM-1, 2, 3, 5, 7, and 9 had cefcanel MICs of 16 µg/ml. Although cefcanel inhibited gram-positive species as well as or at lower concentrations than other cephalosporins, it lacked activity against gram-negative species that produced common plasmid beta-lactamase although it inhibitedHaemophilus influenzae carrying TEM-1.     

In vitro activity of OPC-17116 compared to other broad-spectrum fluoroquinolones

The in vitro activity of OPC-17116 was compared to that of five similar fluoroquinolones (ciprofloxacin, enoxacin, norfloxacin, ofloxacin and temafloxacin). A total of 700 isolates from recent cases of clinical bacteremia were tested. Fifty additional stock strains with well-characterized resistance mechanisms were also processed. The minimal concentrations inhibiting 90 % of strains (MIC90) ofEnterobacteriaceae species were for OPC-17116 0.015–0.5 µg/ml and for ciprofloxacin 0.015–0.25 µg/ml.Moraxella catarrhalis, Haemophilus influenzae andNeisseria gonorrhoeae were very susceptible to OPC-17116 (MIC90 0.015 µg/ml) thus being fourfold more active than ciprofloxacin. For all -hemolytic streptococci and pneumococci OPC-17116 MICs were 0.5 µg/ml. The most resistant enteric bacilli were among theCitrobacter freundii andProvidencia rettgeri strains (MIC90 0.5 µg/ml).Pseudomonas aeruginosa strains were comparably susceptible to OPC-17116 (MIC90 0.5 µg/ml). Low pH and CO₂ incubation had an adverse effect on OPC-17116 MICs, and resistance development was documented among current clinical isolates of staphylococci, pseudomonas and someEnterobacteriaceae.     

Multicentre comparative study on the antibacterial activity of FK-037, a new parenteral cephalosporin

The in vitro antibacterial activity of FK-037, a new parenteral cephalosporin structurally related to cefpirome and cefepime, was compared with that of cefotaxime, ceftazidime, aztreonam, cefpirome, cefepime, imipenem and meropenem against 1,837 clinical isolates obtained from three Spanish hospitals. FK-037 inhibited 90 % ofEnterobacteriaceae isolates at 0.25 µg/ml, with the exception ofEnterobacter aerogenes (MIC90 1 µg/ml),Enterobacter cloacae andCitrobacter freundii (MIC90 8 µg/ml). In cefotaxime-and ceftazidime-resistantKlebsiella pneumoniae strains producing SHV-2 and SHV-6 -lactamases, the activity of FK-037, cefpirome and cefepime was similar (MIC range 0.25–32 µg/ml). InEnterobacteriaceae strains hyperproducing chromosomally inducible -lactamases, FK-037 (MIC90 range, 0.25–8 µg/ml) was 8- to 16-fold more active than cefotaxime and ceftazidime but two- to eightfold less active than cefpirome and cefepime. FK-037 and cefpirome were twofold more active than ceftazidime and cefepime againstPseudomonas aeruginosa isolates, with MIC90 values of 16 µg/ml. The activity of FK-037, cefpirome and cefepime was two- to eightfold lower in ceftazidime-resistant derepressedPseudomonas aeruginosa mutants. FK-037 (MIC range, 0.12–2 µg/ml) and the other -lactam agents tested were active against methicillin-susceptible staphylococci; however, only cefpirome and, particularly, FK-037 (MIC90 of 32 µg/ml) displayed some activity against methicillin-resistant strains. In penicillin-susceptible,-intermediate and -resistantStreptococcus pneumoniae isolates, the MIC90s of FK-037 were 0.03, 0.5 and 1 µg/ml, respectively. The corresponding values forStreptococcus viridans isolates were 0.12, 1 and 8 µg/ml, respectively. In bothStreptococcus pneumoniae andStreptococcus viridans isolates, FK-037 displayed activity similar to that of cefotaxime and cefpirome and slightly higher than that of cefepime.     

In vitro activity of Ro 09-1428 compared to other cephalosporins

The in vitro activity of Ro 09-1428, a new catechol-type parenteral cephalosporin, was compared to that of ceftazidime, E-1040, cefpirome and cefepime against gram-positive and gramnegative organisms. Ro 09-1428 inhibited group A streptococci at 0.12 µg/ml, and group B, C and G streptococci andStreptococcus pneumoniae at 0.5 µg/ml, whereas forStaphylococcus aureus Ro 09-1428 had MICs of 8–16 µg/ml similar to ceftazidime and E-1040. AgainstPseudomonas aeruginosa Ro 09-1428 was the most active agent, inhibiting isolates at 0.12–2 µg/ml, and inhibited ceftazidime-resistant isolates. The majority ofEscherichia coli, Klebsiella spp.,Proteus mirabilis, Citrobacter diversus, Providencia, Salmonella andShigella were inhibited by 0.5 µg/ml as with the other cephalosporins. For mostCitrobacter freundii andEnterobacter cloacae Ro 09-1428 had higher MICs of 4–16 µg/ml; most ceftazidime-resistant isolates of these species were resistant. Anaerobes, enterococci andListeria monocytogenes were resistant to Ro 09-1428. Ro 09-1428 was not hydrolyzed by TEM-1, TEM-2,Staphylococcus aureus PC-1,Moraxella catarrhalis Bro-1,Enterobacter P-99,Pseudomonas aeruginosa Sabath-Abraham orKlebsiella beta-lactamases, but was hydrolyzed by TEM-3, TEM-7 and TEM-9. Ro 09-1428 was markedly less active at an acid pH.     

Comparative in vitro activity of the new fluoroquinolone BMY-40062

The results are presented of comparative in vitro susceptibility testing of BMY-40062, a new fluorinated quinolone which contains a tetrabutyl moiety at N-1 and a piperazinyl group at C-7. BMY-40062 inhibited 90 % ofEnterobacteriaceae strains at < 0.5 µg/ml, being either equal in activity to ciprofloxacin or two- to four-fold less active, depending upon the species. BMY-40062 was as active as ciprofloxacin againstPseudomonas aeruginosa (MIC90 0.5 µg/ml) and inhibited most other strains ofPseudomonas species at < 1 µg/ml. It was more active than ciprofloxacin or ofloxacin against hemolytic streptococci andStreptococcus pneumoniae, 90 % of strains being inhibited at < 0.5 µg/ml. MICs increased in the presence of 9 mM Mg²⁺ and at pH 5.5. The frequency of spontaneous mutation was low forEnterobacteriaceae, Pseudomonas aeruginosa andStaphylococcus aureus (10^–10), but repeated exposure to BMY-40062 caused selection of resistant isolates. Clinical isolates ofPseudomonas aeruginosa resistant to ciprofloxacin and ofloxacin were resistant to BMY-40062.     

In vitro activity of PD 117596-2, a broad-spectrum difluoroquinolone

The activity of PD 117596-2, a novel quinolone, was compared to that of other quinolones, ceftazidime, imipenem and gentamicin. PD 117596-2 inhibited mostEnterobacteriaceae at concentrations <0.25 µg/ml, being equal or superior in activity to ciprofloxacin and 2- to 4-fold more active than ofloxacin. It inhibited ceftazidime-resistantEnterobacter spp.,Citrobacter spp. andSerratia marcescens. The MIC90 forPseudomonas aeruginosa, including strains with imipenem MICs of 8 µg/ml and gentamicin MICs > 16 µg/ml, was 0.25 µg/ml. PD 117596-2 was more active than ciprofloxacin againstPseudomonas cepacia andPseudomonas maltophilia, and it inhibitedNeisseria gonorrhoeae andHaemophilus influenzae at < 0.03 µg/ml. PD 117596-2 inhibited staphylococci at 0.5 µg/ml, being 2-fold superior to other quinolones, and with an MIC of 0.25 µg/ml was more active against group A, B, C and G streptococci andStreptococcus pneumoniae. MICs forBacteroides spp. were 2 µg/ml compared to 8–32 µg/ml for other agents. The frequency of spontaneous resistance was low (< 10^–10). Differences in MICs and MBCs were within one dilution, and there was a minimal effect of inoculum size. Although PD 117596-2 was less active at pH 5.5, MICs were < 0.5 µg/ml.     

In vitro activity and beta-lactamase stability of the new oral cephalosporin Bay v 3522

The activity of the new oral cephalosporin Bay v 3522 was compared to that of six other beta-lactam agents. Bay v 3522 inhibited methicillin-susceptibleStaphylococcus aureus andStaphylococcus epidermidis at 2 µg/ml, compared to MICs of 8 µg/ml for the other cephalosporins tested. It was more active againstStreptococcus pyogenes (MIC 0.06 µg/ml) than cefuroxime, cefixime, cephalexin and cefaclor. Groups B, C and G streptococci were inhibited at 0.12 µg/ml, while the MIC90 forStreptococcus bovis and viridans streptococci was 0.5 and 2 µg/ml, respectively. The MIC90 for enterococci andListeria monocytogenes was 8 µg/ml.Clostridium perfringens was inhibited by 0.12 µg/ml, but mostBacteroides spp. were resistant. The MIC90 for beta-lactamase positiveEscherichia coli (producing primarily TEM-1) was >64 µg/ml and for beta-lactamase negative strains 16 µg/ml. The MIC90 for high-level beta-lactamase producingKlebsiella pneumoniae was >64 µg/ml versus 4 µg/ml for other isolates. The MIC90 forMoraxella catarrhalis was 2 µg/ml, forHaemophilus influenzae 1 µg/ml, and forNeisseria gonorrhoeae 4 µg/ml.Enterobacter cloacae, Citrobacter freundii, Proteus mirabilis, Providencia spp. andPseudomonas aeruginosa were resistant. Bay v 3522 was destroyed by TEM-1, SHV-1, TEM-3 and P99 beta-lactamases.     

In vitro activity of amphotericin B,flucytosine and fluconazole against yeasts causing bloodstream infections

The in vitro activity of amphotericin B, flucytosine and fluconazole against 95 yeasts causing fungemia in a single institution over the last eight years was determined by a broth macromethod recommended by the National Committee for Clinical Laboratory Standards. All strains were inhibited by amphotericin B concentrations of 1 µg/ml. With flucytosine in most species the MIC50 was between 0.12 and 0.25 µg/ml and the MIC90 was between 0.25 and 1 µg/ml. One exception with flucytosine wasCandida krusei, with an MIC50 and MIC90 of 16 µg/ml and 32 µg/ml, respectively. Overall, 12 % of the isolates needed at least 8 µg/ml of fluconazole to be inhibited. Fluconazole was very active againstCandida albicans, Candida tropicalis andCryptococcus neoformans, with MIC50 ranging from 0.12 to 0.5 µg/ml and MIC90 of 1 µg/ml, and somewhat less active againstCandida parapsilosis (MIC50 of 1 µg/ml and MIC90 of 4 µg/ml). Fluconazole exhibited poor in vitro activity againstCandida krusei (MIC50 and MIC90 of 64 µg/ml) andTorulopsis glabrata (MIC50 of 4 µg/ml and MIC90 of 16 µg/ml). High MICs of fluconazole were found for four strains ofCandida albicans, one with an MIC of 4 µg/ml and three (5.7 %) with MICs of 16 µg/ml. Previous exposure to fluconazole could be demonstrated in two of these strains. Further work must be done in order to determine appropriate breakpoints of antifungal agents, to assess the clinical relevance of azole resistance in yeasts causing bloodstream infections and to identify risk factors for infections with azole-resistant yeasts.     

Interpretive criteria and quality control for antimicrobial susceptibility tests of levofloxacin

To confirm preliminary interpretive breakpoints for prototype 5 µg levofloxacin disks, 490 strains were tested in vitro using commercially manufactured disks. For in vitro susceptibility testing, 5 µg levofloxacin disks can be used with interpretive criteria of 12 mm for resistant (MIC 8.0 µg/ml) and 16 mm for susceptible (MIC 2.0 µg/ml). Proposed quality control limits for tests of levofloxacin are as follows:Escherichia coli ATCC 25922, zones 29–37 mm or MIC 0.008–0.03 µg/ml;Pseudomonas aeruginosa ATCC 27853, zones 19–26 mm or MIC 0.5–2.0 µg/ml;Staphylococcus aureus ATCC 25923, zones 24–31 mm;Staphylococcus aureus ATCC 29213, MIC 0.06–0.25 µg/ml andEnterococcus faecalis ATCC 29212, MIC 0.25–2.0 µg/ml.     

In vitro activity of temafloxacin,a new difluoro quinolone antimicrobial agent

Temafloxacin, a new difluoro quinolone, inhibited the majority ofEnterobacteriaceae at 1µg/ml. It was 4–8-fold less active than ciprofloxacin and 2-fold less active than ofloxacin. Cefotaxime and imipenem-resistant isolates such asEnterobacter cloacae, Citrobacter freundii, Pseudomonas aeruginosa, andAcinetobacter spp. were inhibited. Temafloxacin inhibitedNeisseria, Branhamella, andHaemophilus species at < 0.25µg/ml. Methicillin-susceptible and methicillin-resistantStaphylococcus aureus, Staphylococcus epidermidis andClostridium spp. were inhibited at concentrations less or equal to that of ciprofloxacin and ofloxacin.     

In vitro activity of E-4868, a new trifluoroquinolone,compared to six similar compounds

The compound E-4868 (Laboratorios Dr. Esteve) is a trifluoro, 7-azetidinyl quinolone with properties resembling those of other fluoroquinolones. Its activity in vitro was compared to that of six other similar drugs against more than 700 nosocomial isolates using standard methods. The MIC50s of E-4868 for enteric bacilli ranged from 0.015 to 0.25 µg/ml, being highest forProvidencia spp.Pseudomonas aeruginosa strains were two-fold more susceptible to E-4868 than to ofloxacin. MICs of E-4868 forHaemophilus influenzae, Moraxella catarrhalis and pathogenicNeisseria spp. were all 0.12 µg/ml. E-4868 was equal in activity to or eight-fold more active than ciprofloxacin against gram-positive cocci. The MICs of E-4868 for pneumococci were all 0.5 µg/ml but anaerobes such asBacteroides fragilis were generally less susceptible (MIC90, 4 µg/ml). There was almost complete cross-resistance to several other fluoroquinolones. Resistant mutants were selected by a multiple passage technique but the rate of mutation to resistance was very low (< 10^–8) at an 8 x MIC.     

Comparative in vitro activity of the new oxazolidinones DuP 721 and DuP 105 against Staphylococci and Streptococci

The in vitro activity of DuP 721 and DuP 105, two orally active members of the oxazolidinones, was compared with that of glycopeptides and ciprofloxacin against 185 gram-positive isolates. Ninety percent ofStaphylococcus aureus isolates, including penicillin- and methicillin-resistant strains, were inhibited by DuP 721 at 1 µg/ml and by DuP 105 at 16 µg/ml; DuP 721 inhibited 90% of coagulasenegative staphylococci tested at 1 µg/ml. The MIC90 forStreptococcus faecalis was 4 µg/ml with DuP 721 and 16 µg/ml with DuP 105; DuP 721 inhibited 90% of -hemolytic streptococci of group A at 0.5 µg/ml. Similar results on selected strains were obtained by continuously recording the optical density of cultures.     

In vitro activity of FCE 22101, imipenem,and ceftazidime against over 6,000 bacterial isolates and MIC quality control limits of FCE 22101

Six geographically separate laboratories within the USA tested 6,198 bacterial isolates against FCE 22101 (a penem), imipenem (a carbapenem) and ceftazidime (a third-generation cephalosporin). Ninety-three percent of 2,749Enterobacteriaceae were inhibited by FCE 22101, while 95 % were susceptible to ceftazidime and 99 % were susceptible to imipenem. FCE 22101 had little activity againstPseudomonas spp. but was active against most gram-positive pathogens, including enterococci. FCE 22101 MICs for standard quality control strains were defined as 0.5–2.0µg/ml forEscherichia coli ATCC 25922, 2–8µg/ml forEnterococcus faecalis ATCC 29212 and 0.06–0.25µg/ml forStaphylococcus aureus ATCC 29213.     

Characterization of penicillinase-producing strains ofNeisseria gonorrhoeae

Twenty-three penicillinase-producing strains ofNeisseria gonorrhoeae were characterized. All strains showed hybridization with a TEM-1 probe and production of a TEM-1 type beta-lactamase (pI 5.4) on isoelectric focusing. Eight strains also showed a beta-lactamase band of pI 5.5. The penicillin MICs for the strains producing only TEM-1 were in the range 4–16 µg/ml; MICs of the strains with the additional pI 5.5 band were128 µg/ml for seven strains and 4 µg/ml for an arginine-hypoxanthine dependent strain. The association of the high MICs with the presence of the pI 5.5 band was statistically significant. The pI 5.5 band could represent a new beta-lactamase type or a TEM-1 mutant.     

Quality control parameters and interpretive criteria for in vitro susceptibility tests with the macrolide azithromycin

Quality control parameters for broth microdilution and disk diffusion susceptibility tests were defined and the interpretive criteria for disk diffusion tests reviewed. For interpretation of tests with 15 µg azithromycin disks, the following criteria are recommended: 19 mm for the susceptible category (MIC2.0 µg/ml) and 15 mm for the resistant category (MIC8.0 µg/ml). Using these criteria, there was 97 % overall agreement between broth dilution and disk diffusion tests;Haemophilus influenzae isolates were susceptible to azithromycin by both methods. The quality control strainStaphylococcus aureus ATCC 25923 gave zones of 21 to 26 mm in diameter in a six-laboratory collaborative study. In azithromycin broth microdilution tests the following MIC control limits are recommended:Escherichia coli ATCC 25922, 2.0–8.0 µg/ml;Staphylococcus aureus ATCC 29213, 0.25–1.0 µg/ml; andEnterococcus faecalis ATCC 29212, 1.0–4.0 µg/ml.Collaborating investigators contributing data to the quality control studies include P. C. Fuchs, St. Vincent Hospital and Medical Center, Portland, Oregon; S. D. Allen, Indiana University Medical Center, Indianapolis, Indiana; E. H. Gerlach, St. Francis Regional Medical Center, Wichita, Kansas; J. A. Washington, The Cleveland Clinic Foundation, Cleveland, Ohio; L. B. Reller, University of Colorado Medical Center, Denver, Colorado, USA.     

Comparative in vitro activity of the new difluoro-quinolone temafloxacin (A-62254) against bacterial isolates from cancer patients

The in vitro activity of temafloxacin, a new difluoro quinolone agent, against 725 bacterial isolates representing 32 species was evaluated in comparison with that of ciprofloxacin. Temafloxacin inhibited the majority ofEnterobacteriaceae isolates at a concentration of0.5 µg/ml. It was also extremely active againstAcinetobacter spp. andAeromonas hydrophila. Its activity was 2–8fold less than that of ciprofloxacin against most gram-negative isolates. Methicillin-susceptible and methicillin-resistantStaphylococcus aureus, coagulase-negativeStaphylococcus spp.,Streptococcus spp.,Listeria monocytogenes, Bacillus spp. and group JK corynebacteria were inhibited at concentrations equal to that of ciprofloxacin.     

In vitro activity of the new glycopeptide decaplanin

The activity of decaplanin, a new glycopeptide, was compared to that of vancomycin, teicoplanin and daptomycin. Decaplanin was two- to four-fold less active than vancomycin, teicoplanin and daptomycin againstStaphylococcus aureus andStaphylococcus epidermidis, with an MIC90 of 2 µg/ml for methicillin-susceptible and 4 µg/ml for methicillin-resistant isolates. Decaplanin had activity similar to that of vancomycin againstStreptococcus pyogenes, Streptococcus agalactiae, group C and G streptococci, with an MIC90 of 0.12 µg/ml. It was less active than the other agents against the viridans group streptococci (MIC90 4 µg/ml). The activity of decaplanin against enterococci (MIC90 4 µg/ml) was similar to that of vancomycin.Clostridium spp. were inhibited by 0.5 µg/ml, peptostreptococci and peptococci by 0.25 µg/ml. Decaplanin was active from pH 5.5 to 7.5. Inoculum size had a minimal effect on MICs, and increased concentrations of Ca²⁺ and Mg²⁺ and 50 % serum did not alter MICs or MBCs.     

In vitro antimicrobial susceptibility of viridans streptococci isolated from blood cultures

The susceptibility of 211 viridans streptococci isolated from blood cultures to eight antimicrobial agents was determined. All the isolates were susceptible to cefotaxime, ceftriaxone, imipenem and vancomycin. Thirty eight percent of the isolates were resistant to penicillin (MICs 0.25 µg/ml). Tetracycline resistance was found in 41 % of the isolates and in 7 % of these strains tetracycline resistance was combined with erythromycin resistance. FiveStreptococcus mitis isolates exhibited increased (MIC 64 µg/ml and 128 µg/ml) or high-level (MIC 500 µg/ml) resistance to gentamicin, kanamycin and tobramycin. Four of these isolates were also resistant to penicillin (MICs 16–32 µg/m). In vitro synergy was not demonstrated for combinations of penicillin and gentamicin against threeStreptococcus mitis isolates with gentamicin MICs of 1000, 128 and 64 µg/ml. Results of this study indicate the importance of monitoring antibiotic resistance trends in viridans streptococci particularly with respect to penicillin and aminoglycoside resistance.     

In vitro selection of resistance to vancomycin in bloodstream isolates ofStaphylococcus haemolyticus andStaphylococcus epidermidis

The purpose of the study was to determine whether vancomycin-resistant strains ofStaphylococcus haemolyticus could be selected regardless of the initial MIC of vancomycin. Twenty-one bloodstream isolates ofStaphylococcus haemolyticus were studied by broth and agar selection methods. The broth method selected strains for which MICs of vancomycin ranged from 4 to 32 µg/ml and MBCs from 16 to>128 µg/ml. The agar method selected strains for which MICs ranged from 8 to 32 µg/ml and MBCs from 8 to>128 µg/ml. For comparison, seven strains ofStaphylococcus epidermidis were evaluated by the agar selection method. Final MICs of vancomycin ranged from 8 to 16 µg/ml; MBCs ranged from 16 to 64 µg/ml. Clearly, in vitro exposure to vancomycin can select strains ofStaphylococcus haemolyticus andStaphylococcus epidermidis for which MIC values are beyond the susceptible breakpoint.     

Comparative in vitro activity of cefdinir (CI-983; FK-482) against staphylococci,gram-negative bacilli and respiratory tract pathogens

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 staphylocci, gram-negative bacilli and common respiratory tract pathogens. Cefdinir (MIC90 2.0 µg/ml) was more active than cefixime (MIC90 >64 µg/ml) and equally as active as cefuroxime (MIC90 2.0 µg/ml) against oxacillin-susceptible staphylococci. Cefdinir was active againstHaemophilus influenzae, including -lactamase producers (MIC90 0.5 µg/ml),Moraxella catarrhalis (MIC90 0.12 µg/ml),Streptococcus pneumoniae (MIC90 0.06 µg/ml) andStreptococcus pyogenes (MIC90 0.06 µg/ml). The activity of cefdinir against gram-negative bacilli was variable; organisms with chromosomal cephalosporinases were often resistant.