Quality control guidelines for Haemophilus test medium MIC susceptibility tests with cefmetazole, cefpodoxime, CI-960 (PD127391, AM-1090), and RU29246.
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4-Quinolones↗
Biomedical subjects
M E Erwin
Publications and source records attributed to M E Erwin.
In vitro evaluation of GR69153, a novel catechol-substituted cephalosporin.
GR69153 is a C-7 catechol cephalosporin with a broad spectrum of activity against members of the family Enterobacteriaceae (MICs for 50% of strains tested [MIC50s], 0.008 to 0.5 micrograms/ml), Staphylococcus aureus (MIC50, 4 micrograms/ml), Pseudomonas aeruginosa (MIC50, 0.25 micrograms/ml), Haemophilus influenzae (MIC50, 0.03 micrograms/ml), Neisseria gonorrhoeae (MIC50, 0.03 micrograms/ml), and Acinetobacter spp. (MIC50, 2 micrograms/ml). Potent GR69153 activity was also demonstrated against Moraxella catarrhalis, pneumococci, beta-hemolytic streptococci, gram-positive anaerobes, and most species of coagulase-negative staphylococci. The activity of GR69153 was generally two- to fourfold greater than that of ceftazidime. Resistance level GR69153 MICs for 90% of strains tested (greater than or equal to 32 micrograms/ml) were found most often among Citrobacter freundii, Enterobacter spp. and Morganella morganii strains. GR69153 did not significantly inhibit enterococci, Xanthomonas maltophilia, the Bacteroides fragilis group, Corynebacterium jeikeium, or Listeria monocytogenes. GR69153 was bactericidal and was generally beta-lactamase stable, and MICs were only slightly increased by high inoculum concentrations. Activity was enhanced in an iron-deficient medium, and a modest MIC difference attributed to iron availability was noted between standard agar and broth test results. GR69153 was confirmed to be a potent, catechol-substituted cephalosporin with a spectrum slightly wider than that of ceftazidime, but it was less active than cefpirome or imipenem against some gram-positive pathogens and anaerobes.
Bacteria↗
In vitro comparison of GR69153, a novel catechol-substituted cephalosporin, with ceftazidime and ceftriaxone against 5,203 recent clinical isolates.
The activity of GR69153, a novel catechol-substituted cephalosporin, was compared with those of ceftazidime and ceftriaxone in a multicenter study against 5,203 fresh clinical isolates of gram-negative and gram-positive bacteria. GR69153 was generally very active at concentrations equivalent to or two- to fourfold lower than those of ceftazidime and ceftriaxone against gram-negative bacilli other than Citrobacter freundii, Enterobacter cloacae, and Xanthomonas maltophilia. Against Pseudomonas aeruginosa, MICs of GR69153 and ceftazidime for 50% of isolates tested (MIC50s) were, respectively, 1 and 2 micrograms/ml; the corresponding MIC90s were 4 and 16 micrograms/ml. Although MIC50s of GR69153 for staphylococci were two- to eightfold lower than those of ceftazidime or ceftriaxone, MIC90s against staphylococci and enterococci were greater than or equal to 16 micrograms/ml for all three compounds. Quality control MIC ranges for reference strains are proposed for the broth microdilution method on the basis of the GR69153 data derived from this multicenter study.
Bacteria↗
Disk diffusion susceptibility test interpretive criteria for GR69153, a new catechol-substituted cephalosporin.
GR69153 disk diffusion tests with 10- and 30-micrograms disks were evaluated against 383 rapidly growing aerobic pathogens. Very high absolute agreement (96.1 to 98.1%) was observed between the MICs and disk zone diameters, and no false-susceptible results were encountered with the proposed criteria. The 30-micrograms GR69153 disk with a susceptible-zone diameter of greater than or equal to 17 mm (MIC correlate, less than or equal to 8 micrograms/ml) and a resistant-zone diameter of less than or equal to 13 mm (MIC correlate, greater than 16 micrograms/ml) is recommended. GR69153 had a spectrum of activity slightly wider than that of ceftazidime against the species tested.
Ceftazidime↗
Interpretive criteria and quality control guidelines for Neisseria gonorrhoeae susceptibility test standardization for cefotetan.
Cefotetan was tested in a multilaboratory study to standardize susceptibility testing criteria and quality control guidelines for Neisseria gonorrhoeae. Cefotetan was most active against penicillinase-producing and penicillin-susceptible strains (MIC for 50% of strains tested, 0.5 micrograms/ml) and was least active against the chromosomally resistant isolates (MIC for 50% of strains tested, 2 micrograms/ml). The recommended 30-micrograms disk cefotetan interpretive criteria were as follows: susceptible at greater than or equal to 26 mm (less than or equal to 2 micrograms/ml), intermediate at 20 to 25 mm (4 micrograms/ml), and resistant at less than or equal to 19 mm (greater than or equal to 8 micrograms/ml). Quality control guidelines for agar dilution and disk diffusion tests were established by using numerous GC agar lots, three cefotetan 30-micrograms disk lots, two quality control organisms, and a volume of tests consistent with National Committee for Clinical Laboratory Standards M23-T guidelines.
Cefotetan↗
In vitro activity of clarithromycin (TE-031, A-67268) and 14OH-clarithromycin alone and in combination against Legionella species.
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Clarithromycin↗
Antimicrobial spectrum of cefpirome combined with tazobactam against the Bacteroides fragilis group.
Cefpirome, a so-called fourth-generation cephalosporin, was tested alone and in combination with the sulfone beta-lactamase inhibitor, tazobactam, against 63 members of the Bacteroides fragilis group. The cefpirome MIC50 was only 64 micrograms/ml, but the MIC was reduced eightfold with tazobactam (2:1 ratio). The addition of tazobactam to cefpirome or the use of metronidazole as a codrug appear to be alternative choices to enhance the antianaerobic spectrum. Over 98% of strains had cefpirome-tazobactam MICs of less than or equal to 32 micrograms/ml.
Bacteroides↗
Cefmetazole and trospectomycin in vitro susceptibility testing interpretive criteria and quality control guidelines for Neisseria gonorrheae.
Cefmetazole and trospectomycin were tested in a multilaboratory trial to establish Neisseria gonorrhoeae susceptibility testing criteria and quality control (QC) guidelines. Cefmetazole was active against the penicillinase-producing isolates and has an MIC90 of 16 micrograms/ml, the breakpoint MIC previously used for nonfastidious species. However, a single-dose gonorrhea regimen (1 g i.m.) would require a lower less than or equal to 2 micrograms/ml breakpoint with a correlate zone (greater than or equal to 33 mm) consistent with similarly used cephamycins (cefoxitin and cefotetan). An intermediate category was proposed for MICs greater than 2-4 micrograms/m (28-32 mm) pending more clinical experience with higher and/or prolonged cefmetazole dosing regimens. Trospectomycin was active (MIC90, 8 micrograms/ml) against all spectinomycin-susceptible gonococci. A susceptible breakpoint MIC of less than or equal to 16 micrograms trospectomycin per milliliter was proposed with a correlate zone diameter of greater than or equal to 17 mm. An intermediate category was also suggested for trospectomycin at 32 micrograms/ml (14-16 mm). QC guidelines were established for 30-micrograms cefmetazole and 30-micrograms trospectomycin disk diffusion tests and the GC agar base MICs using a multilaboratory study design consistent with National Committee for Clinical Laboratory Standards (NCCLS) M23-T guidelines. Both drugs were stable in GC agar plates for 21 days stored at 2 degrees-5 degrees C.
Cefmetazole↗
In vitro activity of RU29246. The metabolite of a new HR916 cephalosporin ester.
Compound RU29246 (RU) is the active metabolite of an orally absorpted cephalosporin ester HR916. The RU spectrum of activity includes the majority of Enterobacteriaceae species, Haemophilus influenzae, pathogenic Neisseria spp., Moraxella catarrhalis, Acinetobacter antiratus, staphylococci, and Streptococcus spp. Pseudomonas species and enterococci were routinely resistant to RU. The RU spectrum was most similar to cefixime against the Gram-negative bacilli and to cefuroxime against the Gram-positive organisms. RU was bactericidal and its mean inhibitory concentrations (MICs) were not greatly increased by high inoculum concentrations. Many strains producing various beta-lactamases generally remained susceptible to RU by MIC tests. However, isolates with extended broad spectrum beta-lactamases capable of hydrolyzing cefotaxime and ceftazidime were also resistant to RU. Broth and agar RU MICs were comparable. Its activity was increased against enterococci in the presence of blood products.
Anti-Bacterial Agents↗
Antimicrobial activity of three investigational oral cephalosporins (BK-218, cefdinir, and RU29246) against Legionella.
Three new, orally administered cephalosporins (BK-218, cefdinir, RU29246) were tested against 13 representative strains of Legionella. Cefdinir was most active [50% minimum inhibitory concentration (MIC50), 1 micrograms/ml], a potency comparable to the reference drug cefixime and eightfold less active than erythromycin. BK-218 was the least active cephalosporin (MIC50, 8 micrograms/ml) or 100-fold less potent than rifampin. These investigational cephems appear poorly suited by activity assays for Legionellosis therapy.
Anti-Bacterial Agents↗
Antimicrobial activity of E-1040, a novel thiadiazolyl cephalosporin compared with other parenteral cephems.
E-1040, a new parenteral fourth-generation cephalosporin, was tested against greater than 600 bacteremic pathogens and compared with cefotaxime, ceftazidime, and cefpirome. E-1040 activity against Staphylococcus aureus was comparable (MIC90, 8 micrograms/ml) to ceftazidime, but inferior to cefotaxime (MIC90, 2 micrograms/ml) and cefpirome (MIC90, 0.5 microgram/ml). beta-Hemolytic streptococci and most Gram-positive anaerobes were also susceptible to E-1040. Some strains of coagulase-negative staphylococci, all oxacillin-resistant Staphylococcus spp., enterococci, and Bacteroides fragilis group strains were resistant to E-1040 (MIC90, greater than 64 micrograms/ml). Comparative tests for E-1040 and the three other cephalosporins against pseudomonads and nonenteric Gram-negative bacilli showed E-1040 to be generally most active. The E-1040 MIC90 for Pseudomonas aeruginosa was 1 microgram/ml and for ceftazidime it was 4 micrograms/ml. Haemophilus influenzae, Moraxella catarrhalis, and Neisseria spp. has E-1040 MIC90s ranging from 0.12 to 2 micrograms/ml. Neisseria gonorrhoeae, strains resistant to penicillin, did not have markedly elevated E-1040 MICs compared with penicillin-susceptible strains. Enterobacteriaceae species had all MICs of less than or equal to 8 micrograms/ml for E-1040 and cefpirome, indicating activity against strains producing stably derepressed beta-lactamases. E-1040 appeared to be beta-lactamase stable, little influenced by testing systems or media, and was bactericidal. E-1040 seems to have promise as a parenteral beta-lactam for use on strains resistant to "third-generation" cephalosporins and other families of drugs such as aminoglycosides and fluoroquinolones.
Cefotaxime↗
In vitro antimicrobial activity of sparfloxacin (AT-4140, CI-978, PD 131501) compared with numerous other quinolone compounds.
Sparfloxacin (AT-4140, CI-978, PD 131501) was tested against over 800 recent bacteremic strains and compared with ciprofloxacin and six other fluoroquinolones. The 90% minimum inhibitory concentration (MIC90) ranges for the Enterobacteriaceae species were (a) sparfloxacin, 0.03-1 microgram/ml and (b) ciprofloxacin, 0.015-0.25 microgram/ml. Moraxella catarrhalis, Haemophilus influenzae, and Neisseria gonorrhoeae were very susceptible to sparfloxacin (MIC90s, 0.004- less than or equal to 0.03 microgram/ml) and the other comparison drugs. Staphylococcus aureas and other staphylococci were generally susceptible to the tested fluoroquinolones but very susceptible to sparfloxacin and WIN 57273. All beta-hemolytic streptococci, enterococci, and pneumococci had sparfloxacin MICs of less than or equal to 1 microgram/ml. Sparfloxacin was quite active against anaerobic bacteria including Bacteroides fragilis gr. and Gram-positive strains (MIC90s, less than or equal to 2 micrograms/ml). The most resistant enteric bacilli were among Serratia marcescens and the Proteae, especially the Providencia spp. (two- to eightfold higher MICs). Pseudomonas aeruginosa strains were also susceptible to sparfloxacin (MIC90, 2 micrograms/ml). Magnesium ions, CO2 incubation, and low pH had some adverse effect on sparfloxacin MICs, and resistance development was documented among current clinical isolates of staphylococci, pseudomonas, and some enteric species.
Anti-Infective Agents↗
Development of Neisseria gonorrhoeae in vitro susceptibility test methods for cefixime including quality control guidelines.
Cefixime was tested in a multilaboratory study to establish susceptibility testing interpretive criteria and quality control (QC) guidelines for Neisseria gonorrhoeae. Interpretive criteria were established by using triplicate testing of 102 representative gonococcal strains. Only a susceptible category was proposed for cefixime (greater than or equal to 31 mm and less than or equal to 0.25 micrograms/ml) because of very rare, resistant isolates. QC ranges [N. gonorrhoeae American Type Culture Collection (ATCC) 49226] were established using multiple GC agar lots, three disk lots, and a number of test replicates consistent with the National Committee for Clinical Laboratory Standards (NCCLS) M23-T guidelines. Cefixime was stable in GC agar medium for at least 21 days when stored at 2 degrees-5 degrees C. Oral third-generation cephalosporins, such as cefixime, appear to represent potentially useful clinical alternatives to parenteral drugs of the same class for single-dose therapy of gonorrhea.
Cefixime↗
Antimicrobial activity evaluations of two new quinolones, PD127391 (CI-960 and AM-1091) and PD131628.
The in vitro activities of PD127391 and the new fluorinated-4-quinolone, PD131628, were compared with each other and with five similar fluoroquinolones (ciprofloxacin, enoxacin, fleroxacin, norfloxacin, and ofloxacin). A total of 844 isolates mainly from recent clinical bacteremias and additional stock strains with well-characterized resistance mechanisms were tested. PD127391 had slightly more activity than PD131628 (90% minimum inhibitory concentration (MIC90)] 0.008-0.12) against the Enterobacteriaceae, but both were two- to fourfold more potent than ciprofloxacin. PD131628 activity was equal to or greater than PD127391 when tested against Pseudomonas aeruginosa. PD127391 showed greatest activity against Bacteroides fragilis group strains (MIC90, 2 micrograms/ml) when compared with PD131628 (MIC90 greater than 8 micrograms/ml). Both PD127391 (MIC90s, 0.015-1.0 micrograms/ml) and PD131628 (MIC90s, 0.03 - greater than 8 micrograms/ml) were more active than ciprofloxacin against Gram-positive organisms. Altering the medium pH, adding divalent cations (magnesium), and increasing the inoculum concentration to 10(6) colony-forming units per spot adversely effected the activity of both PD127391 and PD131628. Resistance selection and mutational rates to resistance were identical to previously studied drugs in their class.
Anti-Infective Agents↗
In vitro activity evaluations of cefdinir (FK482, CI-983, and PD134393). A novel orally administered cephalosporin.
Cefdinir, a so-called third-generation oral cephalosporin was tested in vitro against over 700 pathogens from patients with bacteremia. Cefdinir was very active against the Enterobacteriaceae with a 50% minimum inhibitory concentration (MIC50) value range of less than or equal to 0.03-8 micrograms/ml. The enteric species having the highest MIC90S (greater than or equal to 16 micrograms/ml) were Citrobacter freundii, and the enterobacters, Morganella morganii, Proteus vulgaris, and Serratia marcescens. Cefdinir was generally two- to fourfold less active than cefixime, but markedly more potent with a wider spectrum compared with older oral cephalosporins, cefaclor or cefuroxime. In contrast to cefixime, cefdinir inhibited Staphylococcus aureus (MIC90, 1 micrograms/ml) and other staphylococci. Pneumococci, beta-hemolytic streptococci, Haemophilus influenzae, Moraxella catarrhalis, and pathogenic Neisseria spp. (MIC90S, 0.12-0.5 micrograms/ml) were cefdinir susceptible, but Pseudomonas aeruginosa, oxacillin-resistant staphylococci and Bacteroides fragilis gr. strains were resistant. Cefdinir was generally bactericidal with a minimal inoculum effect at 10(6) colony-forming units per spot. Cefdinir beta-lactamase hydrolysis by some recently described extended broad spectrum beta-lactamases was suspected. Cefdinir exhibited a wide, balanced spectrum for an oral cephalosporin indicating possible clinical use against susceptible pathogens in respiratory tract, urinary tract, genital and cutaneous infections.
Cefdinir↗
Interpretive criteria for CI-960 (AM-1091, PD127391) disk diffusion tests using 5-microgram disks.
CI-960, a new potent fluoroquinolone, was evaluated to develop disk diffusion susceptibility criteria for a 5-micrograms content disk. Preliminary interpretive zone diameter criteria were proposed for two possible susceptible breakpoint MICs (less than or equal to 1 and less than or equal to 2 micrograms/ml). Both sets of interpretive criteria performed well having 96.8%-98.4% absolute agreement and no false-susceptible errors. The more conservative less than or equal to 1-microgram/ml breakpoint criteria had correlate zones of greater than or equal to 23 mm for susceptible and less than or equal to 19 mm for resistant. These criteria produced no false resistance, whereas 0.7% of strains exhibited major errors at the less than or equal to 2-micrograms/ml breakpoint.
Anti-Infective Agents↗
Haemophilus test medium interpretive criteria for disk diffusion susceptibility tests with cefdinir, cefetamet, cefmetazole, cefpodoxime, cefdaloxime (RU29246, HR-916 metabolite), and trospectomycin.
The disk diffusion zones and the MICs of six newer antimicrobials with significant activity against Haemophilus influenzae were compared using the Haemophilus test medium (HTM) and National Committee for Clinical Laboratory Standards methods. The rank order of potency was cefpodoxime (MIC50, < or = 0.03 micrograms/ml) > cefetamet > cefdinir > cefdaloxime = trospectomycin > cefmetazole (MIC50, 2 micrograms/ml). Susceptible breakpoint interpretive criteria for HTM tests were established that conformed to prior recommendations for each drug when tested against other species. Absolute agreement between methods ranged from 89% to 100% with < or = 1% false-susceptible interpretive errors. The recommended, tentative disk diffusion susceptible interpretive criteria were for 5-micrograms cefdinir disks > or = 20 mm (MIC correlate, < or = 1 micrograms/ml); for 10-micrograms cefetamet disks > or = 18 mm (MIC correlate, < or = 4 micrograms/ml); for 30-micrograms cefetamet disks > or = 21 mm (MIC correlate, < or = 4 micrograms/ml); for 30-micrograms cefmetazole disks > or = 16 mm (MIC correlate, < or = 16 micrograms/ml); for 10-micrograms cefpodoxime disks > or = 21 mm (MIC correlate, < or = 2 micrograms/ml); for 30-micrograms cefdaloxime disks > or = 23 mm (MIC correlate, < or = 2 micrograms/ml) and for 30-micrograms trospectomycin disks > or = 17 mm (MIC correlate, < or = 16 micrograms/ml). beta-Lactamase-negative, ampicillin-resistant (BLNAR) H. influenzae isolates consistently had the highest MICs for each cephalosporin tested.(ABSTRACT TRUNCATED AT 250 WORDS)
Ampicillin Resistance↗
In vitro activity of cefpodoxime compared with other oral cephalosporins tested against 5556 recent clinical isolates from five medical centers.
A multicenter study was conducted in which the in vitro activity of cefpodoxime (the active metabolite of the prodrug ester cefpodoxime proxetil) was compared with those of cefixime, cefuroxime, cefaclor, cefadroxil, and clarithromycin against 5556 recent clinical isolates. Cefpodoxime demonstrated potent activity against members of the Enterobacteriaceae, in particular against species generally resistant to the established oral cephalosporins such as Proteus vulgaris [minimum inhibitory concentration (MIC)50, 0.12 microgram/ml], Providencia rettgeri (MIC50, 0.015 microgram/ml), and Serratia marcescens (MIC50, 2 micrograms/ml). Cefpodoxime was very effective against the fastidious organisms most frequently associated with respiratory infections, such as Streptococcus pneumoniae (MIC90, 0.12 microgram/ml), Haemophilus influenzae (MIC90, 0.12 microgram/ml), and Moraxella catarrhalis (MIC90, 1 microgram/ml). In contrast to other orally administrated third-generation cephalosporins (cefixime or ceftibuten), cefpodoxime demonstrated reasonable activity against oxacillin-susceptible staphylococci, with MIC50 ranging from 1 to 2 micrograms/ml. All cephalosporins tested demonstrated poor activity against Pseudomonas spp., Xanthomonas spp., Enterococcus spp., and oxacillin-resistant staphylococci. Cefpodoxime had the widest spectrum of activity of all tested oral cephalosporins.
Administration, Oral↗