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1.  LY164846 in vitro antimicrobial activity testing, including disk diffusion susceptibility tests using 30-microgram disks. 
A new oral cephalosporin, LY164846 (Eli Lilly & Co., Indianapolis, Ind.), was found to have a unique antimicrobial spectrum confined to methicillin-susceptible Staphylococcus spp., streptococci (except Enterococcus spp.), Haemophilus influenzae, Branhamella catarrhalis, and some anaerobes. Cephalothin in vitro tests (30-microgram disks or dilution) can represent LY164846 for laboratory testing if comparable interpretive breakpoints are applied to strains within the spectrum of LY164846. Organisms not inhibited by LY164846 (MICs greater than or equal to 32 micrograms/ml) were members of the family Enterobacteriaceae, Pseudomonas spp., Acinetobacter spp., enterococci, and some strains of Staphylococcus haemolyticus and of the Bacteroides fragilis group.
PMCID: PMC180430  PMID: 3755018
2.  Antimicrobial activity of Ro 23-9424, a novel ester-linked codrug of fleroxacin and desacetylcefotaxime. 
Ro 23-9424 is a novel ester-linked codrug of fleroxacin (Ro 23-6240; AM-833) and the cefotaxime metabolite desacetylcefotaxime. Its potency was determined against over 1,000 organisms and found to be intermediate between those of the two components. More than 99% of members of the family Enterobacteriaceae were inhibited by greater than or equal micrograms of Ro 23-9424 per ml; its MIC for 50% of strains tested ranged from greater than or equal to 0.06 to 1 micrograms/ml. Staphylococci, streptococci, Branhamella catarrhalis, Corynebacterium jeikeium, Bacillus spp., Haemophilus influenzae, Listeria monocytogenes, and the pathogenic Neisseria spp., including oxacillin-resistant Staphylococcus aureus, beta-lactamase-producing strains, and penicillin-resistant pneumococci, were also inhibited by Ro 23-9424. Pseudomonas aeruginosa, Enterococcus spp., and Bacteroides fragilis group isolates were more refractory to Ro 23-9424 (the MIC for 90% of strains tested was less than or equal to 32 micrograms/ml). Overall, Ro 23-9424 inhibited 97% of the aerobic strains, compared with 90% for ceftazidime and 92% for cefoperazone. Ro 23-9424 was bactericidal, was relatively stable to inoculum effects on MICs at 10(7) CFU/ml, and was determined to be highly active against organisms resistant to fluoroquinolones or ceftazidime. Preliminary quality control guidelines were determined, and a 30-micrograms disk concentration appears to be the most usable form.
PMCID: PMC284260  PMID: 2504106
3.  Cefoperazone (T-1551), a new semisynthetic cephalosporin: comparison with cephalothin and gentamicin. 
The in vitro activity of cefoperazone (T-1551) against almost 9,000 recent clinical isolates at six institutions was tested and compared with that of cephalothin and gentamicin. The modal minimum inhibitory concentrations of cefoperazone were 16- and 4-fold less than those of cephalothin and gentamicin, respectively, against 5,503 strains of Enterobacteriaceae. Species normally resistant to cephalothin, such as indole-positive protease and enterobacters, were almost universally susceptible to cefoperazone. Cefoperazone demonstrated activity comparable to gentamicin against Pseudomonas aeruginosa and other pseudomonads.
PMCID: PMC283865  PMID: 6446879
4.  Antibacterial activity of trospectomycin (U-63366F) and initial evaluations of disk diffusion susceptibility tests. 
The in vitro activities of trospectomycin sulfate were compared with those spectinomycin against 632 aerobic microorganisms, including 66 Neisseria gonorrhoeae isolates. Against species other than gram-negative bacilli, trospectomycin was about 4- to 16-fold more active than spectinomycin. For disk diffusion tests, a 30-micrograms disk is recommended, with tentative zone size breakpoints of less than or equal to 13 mm for resistance (MIC, greater than or equal to 64 micrograms/ml) and greater than or equal to 17 mm for susceptibility (MIC, less than or equal to 16 micrograms/ml).
PMCID: PMC172481  PMID: 2524997
5.  Antimicrobial activity and spectrum of LY146032, a lipopeptide antibiotic, including susceptibility testing recommendations. 
LY146032, a new lipopeptide, was found to have a spectrum of gram-positive antimicrobial activity that includes activity against staphylococci (methicillin susceptible and resistant), beta-hemolytic Streptococcus spp., pneumococci, viridans group Streptococcus spp., anaerobic gram-positive cocci, Clostridium spp., and enterococci. The new lipopeptide was generally bactericidal and showed more rapid killing of Listeria spp. (MIC, 1 to 2 micrograms/ml) and staphylococci than either vancomycin or teicoplanin. The 30-micrograms disk was preferred to the 15-micrograms disk on the basis of the preliminary interpretive criteria for susceptibility which indicated zone diameters of greater than or equal to 16 mm for susceptible strains (MIC, less than or equal to 2.0 micrograms/ml) and greater than or equal to 12 mm for resistant strains (MIC, greater than or equal to 8.0 micrograms/ml). These criteria are valid pending the testing of additional gram-positive strains which have LY146032 MICs of greater than or equal to 8 micrograms/ml.
PMCID: PMC174792  PMID: 3038001
6.  Evaluation of the in vitro activity of BMY-28142, a new broad-spectrum cephalosporin. 
The in vitro activity of BMY-28142, a new cephalosporin, was tested by a broth microdilution system and compared with those of cefotaxime, ceftazidime, cefoperazone, moxalactam, and HR 810 against 747 bacterial isolates, one-third of which were resistant to one or more third-generation cephalosporins. BMY-28142 was the most active drug tested against 326 Enterobacteriaceae with an MIC for 90% of the organisms tested (MIC90) of 1.0 micrograms/ml. Against these Enterobacteriaceae the relative activities were: BMY-28142 greater than HR 810 greater than moxalactam and ceftazidime greater than cefotaxime greater than cefoperazone. For cefotaxime- and cefoperazone-resistant strains, the MIC90 of BMY-28142 was 4.0 micrograms/ml (compared with 0.13 micrograms/ml for susceptible strains). BMY-28142, with an MIC90 of 8.0 micrograms/ml for Pseudomonas aeruginosa, was about half as active as ceftazidime. The relative activities against P. aeruginosa were: ceftazidime greater than BMY-28142 greater than HR 810 greater than cefoperazone greater than moxalactam and cefotaxime. The MIC90 of BMY-28142 against staphylococci was 2.0 micrograms/ml, which was fourfold less active than HR 810, slightly less active than cefotaxime and cefoperazone, and fourfold more active than ceftazidime and moxalactam. BMY-28142 was very active against beta-lactamase-positive and -negative Haemophilus influenzae (MIC90, 0.06 micrograms/ml), Neisseria gonorrhoeae (MIC90, 0.015 micrograms/ml),aand nonenterococcal streptococci. Its activity against Streptococcus faecalis was poor (MIC90, 64 micrograms/ml). BMY-28142 was stable against the several beta-lactamases tested but exhibited little beta-lactamase inhibitory effect.
PMCID: PMC180130  PMID: 3893316
7.  In vitro evaluation of HR810, a new wide-spectrum aminothiazolyl alpha-methoxyimino cephalosporin. 
HR810 (Hoechst-Roussel Pharmaceuticals Inc., Somerville, N.J.) is a new, cyclical-pyridinium cephalosporin that appeared superior to numerous comparison drugs against 658 strains of aerobic and facultative anaerobic bacteria. Seventeen Enterobacteriaceae spp. were tested by broth microdilution methods, and the 50% MICs (MIC50S) and 90% MICs (MIC90s) were 0.03 to 0.12 and 0.03 to 2.0 micrograms/ml, respectively. Only one strain had an MIC greater than 8.0 micrograms/ml (99.6% is considered susceptible). HR810 inhibited 98% of Pseudomonas aeruginosa isolates at less than or equal to 16 micrograms/ml, and the MIC90 for Acinetobacter spp. was 4.0 micrograms/ml. It was also very active against Pseudomonas spp. and Staphylococcus aureus (MIC90, 0.5 micrograms/ml) but marginally active against methicillin-resistant staphylococcal strains (MIC90, 16 micrograms/ml) and enterococcus (MIC90, 32 micrograms/ml). Non-enterococcal streptococci had MIC50s ranging from 0.008 micrograms/ml for Streptococcus pyogenes to 0.12 micrograms/ml for pneumococci. All MICs of HR810 against Haemophilus and Neisseria spp. were less than or equal to 0.03 micrograms/ml (MIC50, 0.002 to 0.008 micrograms/ml). HR810 poorly inhibited beta-lactamases and was very stable against 11 tested beta-lactamases of plasmid (TEM, OXA, SHV-1, and PSE) and chromosomal (K1, K14, P99) types.
PMCID: PMC185628  PMID: 6611135
8.  Compound A49759, the 3-O-demethyl derivative of fortimicin A: in vitro comparison with six other aminoglycoside antibiotics. 
O-Demethylfortimicin A (compound A49759) was tested against 445 bacteria, and the results were compared with those obtained with fortimicin A, amikacin, gentamicin, netilmicin, sisomicin, and tobramycin. A49759 was found to be active and bactericidal against the Enterobacteriaceae, nonfermentative gram-negative bacilli, and Staphylococcus aureus. A49759 was two- to fourfold more active than fortimicin A against most species tested, but generally fourfold less active than amikacin against this population of Pseudomonas aeruginosa (85% inhibited at less than or equal to 16 microgram of amikacin per ml and 85% inhibited at less than or equal to 64 microgram of A49759 per ml). Only amikacin and A49759 were resistant to most aminoglucoside-inactivating enzymes and also had significant antipseudomonal activity. Amikacin was inactivated by aminoglycoside 6'-acetyltransferase, and A49759 was inactivated by aminoglycoside 3-acetyltransferase. The minimal inhibitory concentrations of all tested aminoglycosides were increased by augmenting the inoculum size.
PMCID: PMC284090  PMID: 7447431
9.  In vitro activities of five fluoroquinolone compounds against strains of Streptococcus pneumoniae with resistance to other antimicrobial agents. 
Antimicrobial Agents and Chemotherapy  1996;40(10):2431-2433.
Ciprofloxacin, clinafloxacin, PD 131628, sparfloxacin, and trovafloxacin were tested against 236 strains of Streptococcus pneumoniae, most of which were resistant to other agents. Resistance to multiple antibiotics did not affect the organism's susceptibility to the fluoroquinolones. The fluoroquinolones with in vitro antipneumococcal activity might be particularly useful against strains that are resistant to the more traditional therapeutic agents.
PMCID: PMC163550  PMID: 8891160
10.  In vitro studies of two triazole antifungal agents (voriconazole [UK-109,496] and fluconazole) against Candida species. 
A new triazole derivative (voriconazole or UK-109,496) and fluconazole were tested against 249 isolates of Candida spp. representing six species. Voriconazole was 10 to 100 times more potent than fluconazole. Strains with decreased susceptibility to fluconazole were inhibited by relatively low concentrations of voriconazole.
PMCID: PMC163448  PMID: 8843312
11.  Prevalence of resistance to three fluoroquinolones: assessment of levofloxacin disk test error rates and surrogate predictors of levofloxacin susceptibility. AST Surveillance Group. 
More than 3,000 consecutive clinical bacterial isolates from 10 U.S. medical centers were subjected to standard broth microdilution and disk diffusion tests to determine their susceptibilities to levofloxacin, ofloxacin, D-ofloxacin, and ciprofloxacin. Levofloxacin was confirmed to be twice as active as ofloxacin and to have activity comparable to that of ciprofloxacin, with minor variations in activity against some species. The prevalence of resistant isolates was 7.1% to levofloxacin, 9.3% to ciprofloxacin, and 11.2% to ofloxacin. The susceptibilities of some species to the quinolones were less than those reported in previous studies. Pseudomonas aeruginosa isolates had the greatest variability in their susceptibilities to the three drugs between the participating centers. Two proposed zone size breakpoints for levofloxacin disk tests yielded similar low error rates. Ofloxacin and ciprofloxacin susceptibility test results correlated reasonably well with those of levofloxacin and could be used as surrogate indicators of levofloxacin susceptibility, but that resulted in some serious errors, and thus, direct testing of levofloxacin susceptibility is preferable. Replicate testing of standard quality control strains confirmed the established and proposed quality control parameters for all three quinolones tested.
PMCID: PMC163386  PMID: 8807053
12.  In vitro activities of cefotaxime, ceftriaxone, ceftazidime, cefpirome, and penicillin against Streptococcus pneumoniae isolates. 
Antimicrobial Agents and Chemotherapy  1995;39(10):2193-2196.
The in vitro activities of four extended-spectrum cephalosporins and benzyl penicillin were evaluated against 698 clinical isolates of Streptococcus pneumoniae, including 130 (19%) penicillin-intermediate and 84 (12%) penicillin-resistant strains. Cefotaxime and ceftriaxone were essentially identical in their antipneumococcal activities: both were active against penicillin-susceptible strains and most penicillin-intermediate strains. Cefpirome was twice as potent as cefotaxime and ceftriaxone against penicillin-resistant strains. Ceftazidime was 8- to 16-fold less active than cefotaxime and ceftriaxone against S. pneumoniae in vitro, and thus, its spectrum included only penicillin-susceptible strains.
PMCID: PMC162912  PMID: 8619565
13.  Antibacterial activity of WY-49605 compared with those of six other oral agents and selection of disk content for disk diffusion susceptibility testing. 
The in vitro antimicrobial activity of an oral penem, WY-49605, was compared with those of six other oral antimicrobial agents against 598 bacterial isolates representing 51 different species. WY-49605 exhibited good activity against most gram-positive bacteria and members of the family Enterobacteriaceae. It had little activity against nonfermenting gram-negative bacilli, Enterobacter spp., Serratia spp., enterococci, Staphylococcus haemolyticus, and methicillin-resistant Staphylococcus aureus. Its activity was unaffected by the beta-lactamases of Neisseria gonorrhoeae, Haemophilus influenzae, and staphylococci. Disk diffusion susceptibility tests were performed with 5-, 10-, 15-, and 30-micrograms WY-49605 disks. The 5-micrograms disk is recommended, with tentative breakpoints of > or = 16 mm for susceptibility (MIC, < or = 2.0 microgram/ml) and < or = 12 mm for resistance (MIC, > or = 8.0 micrograms/ml).
PMCID: PMC162765  PMID: 7492088
14.  In vitro activities of a streptogramin (RP59500), three macrolides, and an azalide against four respiratory tract pathogens. 
Broth microdilution tests were carried out with 2,671 respiratory tract isolates from 19 medical centers throughout the continental United States. The tests compared a streptogramin (RP59500) to erythromycin, dirithromycin, clarithromycin, and azithromycin against Streptococcus pneumoniae, S. pyogenes, Haemophilus influenzae, and Moraxella catarrhalis. Against macrolide-susceptible strains, the potency of RP59500 was similar to that of the macrolides: the azalide, azithromycin, was two to four times more potent against H. influenzae. The azalide and three macrolides showed nearly complete cross-resistance. At 2.0 micrograms/ml or less, the streptogramin, RP59500, was active against both macrolide-resistant and -susceptible strains of S. pneumoniae (MIC for 50% of the strains tested, 0.25 microgram/ml; MIC for 90% of the strains tested, 0.5 microgram/ml).
PMCID: PMC162515  PMID: 7695313
15.  Antifungal susceptibility testing of isolates from a randomized, multicenter trial of fluconazole versus amphotericin B as treatment of nonneutropenic patients with candidemia. NIAID Mycoses Study Group and the Candidemia Study Group. 
The antifungal susceptibilities of 232 pathogenic blood stream Candida isolates collected during a recently completed trial comparing fluconazole (400 mg/day) with amphotericin B (0.5 mg/kg of body weight per day) as treatment for candidemia in the nonneutropenic patient were determined both by the National committee for Clinical Laboratory Standards M27-P macrobroth methodology and by a less cumbersome broth microdilution methodology. For amphotericin B, M27-P yielded a very narrow range of MICs (0.125 to 1 microgram/ml) and there were no susceptibility differences among species. For fluconazole, a broad range of MICs were seen (0.125 to > 64 micrograms/ml), with characteristic MICs seen for each species in the rank order Candida albicans < C. parapsilosis approximately equal to C. lusitaniae < C. glabrata approximately equal to C. krusei approximately equal to C. lipolytica. The MIC distribution for C. tropicalis was bimodal and could not be ranked. Both microdilution MICs were within one tube dilution of the M27-P MIC for > 90% of isolates with amphotericin B and for > or = 77% of isolates with fluconazole. For both methods, elevated MICs did not predict treatment failure. In the case of amphotericin B, the MIC range was too narrow to permit identification of resistant isolates. In the case of fluconazole, MICs for isolates associated with failure to clear the bloodstream consistently were equivalent to the median MIC for the given species. Successful courses of therapy were seen with four isolates from four patients despite MICs of > or = 32 micrograms/ml. As MICs obtained by M27-P and similar methods correlate with responsiveness to fluconazole therapy in animal models and in AIDS patients with oropharyngeal candidiasis, the lack of correlation in this setting suggests that the MICs for these isolates are at or below the relevant fluconazole breakpoint for this dose of fluconazole and patient setting and that host factors such as failure to exchange intravenous catheters were more important than MIC in predicting outcome.
PMCID: PMC162481  PMID: 7695326
16.  In vitro activities of 12 orally administered antimicrobial agents against four species of bacterial respiratory pathogens from U.S. Medical Centers in 1992 and 1993. 
Antimicrobial Agents and Chemotherapy  1994;38(10):2419-2425.
Clinical isolates of Haemophilus influenzae, Streptococcus pneumoniae, Streptococcus pyogenes, and Moraxella catarrhalis were gathered from 19 different clinical laboratories throughout the continental United States. The in vitro activities of 12 orally administered antimicrobial agents were compared by broth microdilution tests with 3,151 bacterial isolates. Among 890 H. influenzae isolates, 30% were capable of producing beta-lactamase enzymes (12 to 41% in different medical centers). Most of the 619 beta-lactamase-negative H. influenzae strains were susceptible to ampicillicin (MIC, < or = 1.0 micrograms/ml): 5 strains were intermediate in susceptibility (MIC, 2.0 micrograms/ml) and 1 strain was ampilicillin resistant (MIC, 4.0 micrograms/ml). Ninety-two percent of 698 M. catarrhalis strains were beta-lactamase positive. Of 799 S. pneumoniae isolates, 15% were intermediate in susceptibility to penicillin and 7% were resistant to penicillin. The prevalence of penicillin-susceptible pneumococci in different institutions ranged from 63 to 95%. Only 1% of 764 S. pyogenes isolates were resistant to the macrolides, but 5% of S. pneumoniae isolates were macrolide resistant. Only 71% of 58 penicillin-resistant S. pneumoniae isolates were erythromycin susceptible, whereas 97% of the 622 penicillin-susceptible strains were erythromycin susceptible. Penicillin-resistant pneumococci were also relatively resistant to the cephalosporins and amoxicillin. Penicillin-susceptible pneumococci were susceptible to amoxicillin-clavulanic acid (MIC for 90% of isolates tested [MIC90], < or = 0.12/0.06 microgram/ml), cefixime (MIC90, 0.25 microgram/ml), cefuroxime axetil (MIC90, < or = 0.5 microgram/ml), cefprozil (MIC90, < or = 0.5 micrograms/ml), cefaclor (MIC90, 0.5 microgram/ml), and loracarbef (MIC90, 1.0 microgram/ml). Most strains of the other species remained susceptible to the study drugs other than amoxicillin.
PMCID: PMC284755  PMID: 7840581
17.  Antimicrobial activity and disk diffusion susceptibility testing of Ro 40-6890, the active metabolite of the new cephalosporin ester, Ro 41-3399. 
Ro 40-6890, the active metabolite of Ro 41-3399, was tested against 391 gram-negative and gram-positive clinical isolates. Ro 40-6890 was active against members of the family Enterobacteriaceae, Moraxella catarrhalis, pneumococci, other Streptococcus spp., and methicillin-susceptible staphylococci. Preliminary disk diffusion interpretive zone criteria were calculated for 5-, 10-, and 30-micrograms Ro 40-6890 disks and several possible MIC susceptibility breakpoints. We recommend the use of the 5-micrograms disk and suggest that the following zone diameters be used as breakpoints in clinical trials: susceptible, > or = 21 mm (MIC, < or = 1 microgram/ml); intermediate, 18 to 20 mm (MIC, 2 micrograms/ml); and resistant, < or = 17 mm (MIC, > or = 4 micrograms/ml).
PMCID: PMC187802  PMID: 8494387
18.  Ticarcillin and ticarcillin-clavulanic acid susceptibility tests: error rates for disk tests with consecutively isolated members of the family Enterobacteriaceae. 
A five-laboratory coordinated study was undertaken to determine whether ticarcillin and ticarcillin-clavulanic acid disk susceptibility tests could accurately detect resistance among enteric bacilli. Each facility performed disk tests and broth microdilution susceptibility tests with reagents distributed from a common source, and appropriate controls were included in order to ensure methodologic uniformity. Each institution tested 500 consecutively isolated enteric bacilli against ticarcillin and ticarcillin-clavulanic acid. The prevalence of discrepancies between disk tests and dilution tests with 2,435 unselected enteric bacilli provided a valid estimate of the true error rate for tests with the two disks. The current interpretive criteria for susceptibility tests with ticarcillin and ticarcillin-clavulanic acid disks were found to be reliable; i.e., there were major or very major discrepancies between MIC categories and disk test results for less than 1% of all strains and minor discrepancies for only 5 to 10%. Even lower error rates would occur if the zone size-interpretive criteria were modified, but at this time it is difficult to determine whether the practical problems created by making such changes can be justified by the magnitude of the problem that is being resolved.
PMCID: PMC189241  PMID: 1590679
19.  In vitro susceptibility testing procedures for fosfomycin tromethamine. 
Fosfomycin tromethamine (previously fosfomycin trometamol) is an orally administered fosfomycin which may be used for single-dose therapy of uncomplicated urinary tract infections. Fosfomycin tromethamine, norfloxacin, and trimethoprim-sulfamethoxazole inhibited greater than 90% of 352 bacterial isolates representing 25 different species; trimethoprim and nalidixic acid had narrower spectrums of activity. Strains of Escherichia, Citrobacter, Enterobacter, and Klebsiella species were much more susceptible when glucose-6-phosphate was added to the test medium, but isolates belonging to other genera were not affected.
PMCID: PMC284319  PMID: 1929270
20.  In vitro activities of sparfloxacin, tosufloxacin, ciprofloxacin, and fleroxacin. 
The in vitro activity of sparfloxacin was compared with those of tosufloxacin, ciprofloxacin, and fleroxacin against 730 bacterial isolates representing 49 different species. Sparfloxacin and ciprofloxacin had similar spectra of activity, but sparfloxacin was less active against Pseudomonas aeruginosa and more active against many gram-positive cocci and anaerobic bacteria. Tosufloxacin MICs were generally 8- to 16-fold lower than those for sparfloxacin or ciprofloxacin. All four fluoroquinolones were active against nalidixic acid-susceptible strains of the family Enterobacteriaceae (MIC for 90% of the isolates [MIC90], less than or equal to 0.25 micrograms/ml) but nalidixic acid-resistant strains were less susceptible (MIC90, greater than or equal to 4.0 micrograms/ml). Against Pseudomonas aeruginosa isolates, MIC90s were 1.0 micrograms/ml for tosufloxacin, 2.0 micrograms/ml for ciprofloxacin, and 4.0 micrograms/ml for sparfloxacin. Against Enterococcus faecalis, sparfloxacin and ciprofloxacin MIC90s were 1.0 and 2.0 micrograms/ml, respectively. MIC90s for ciprofloxacin-susceptible Staphylococcus aureus were 0.016 micrograms/ml for tosufloxacin, 0.06 micrograms/ml for sparfloxacin, and 0.5 micrograms/ml for both ciprofloxacin and fleroxacin. With four species of gram-negative bacilli, mutants resistant to two to four times the sparfloxacin MIC occurred spontaneously at frequencies of 10(-7) to 10(-9): single-step high-level resistance was not observed. In vitro-selected sparfloxacin-resistant mutants displayed cross-resistance to other quinolones, as did clinical isolates of ciprofloxacin-resistant S. aureus. Tosufloxacin MICs with broth microdilution methods were four- to eightfold greater than those obtained with agar dilution methods. The two procedures gave comparable results when sparfloxacin or ciprofloxacin was being tested.
PMCID: PMC245135  PMID: 1906696
21.  In vitro antibacterial spectrum of E1040 compared with those of cefpirome and ceftazidime and disk diffusion interpretive criteria for E1040. 
E1040 is a new parenteral cephalosporin which was tested against 690 clinical isolates and compared with cefpirome and ceftazidime. E1040 had the best activity of the three drugs against Pseudomonas aeruginosa, inhibiting 89% of strains at 8.0 micrograms/ml. E1040 demonstrated good activity against members of the family Enterobacteriaceae, including cefpirome-resistant and ceftazidime-resistant strains. E1040 also had good activity against streptococci but much poorer activity against enterococci and staphylococci. When E1040 broth microdilution and disk diffusion susceptibility test results were compared, the 30-micrograms disk was recommended, with the following tentative interpretive criteria: susceptible, greater than or equal to 18 mm (MIC, less than or equal to 8.0 micrograms/ml); intermediate, 15 to 17 mm (MIC, 16 micrograms/ml); and resistant, less than or equal to 14 mm (MIC, greater than or equal to 32 micrograms/ml).
PMCID: PMC171720  PMID: 2193626
22.  Multicenter in vitro evaluation of SM-7338, a new carbapenem. 
A new carbapenem, SM-7338, was compared with imipenem, cefotaxime, and ceftazidime at five medical centers. Nearly 6,000 strains were tested by reference methods of the National Committee for Clinical Laboratory Standards, and SM-7338 inhibited the largest percentage of gram-negative bacilli. Its spectrum included all members of the family Enterobacteriaceae (99.7% were susceptible to less than or equal to 4 micrograms/ml), Pseudomonas spp. (but not Xanthomonas maltophilia), and Acinetobacter spp. The potency and spectrum of SM-7338 against the gram-positive organisms were less than those of imipenem and superior to those of ceftazidime. Only the enterococci and some oxacillin-resistant staphylococci were less susceptible to SM-7338 (MICs for 90% of isolates, greater than or equal to 8 micrograms/ml). Organisms resistant to ceftazidime were generally susceptible to SM-7338 and imipenem (76%). However, for one-third of the imipenem-resistant gram-negative bacilli (MICs, greater than 8 micrograms/ml), SM-7338 MICs were less than or equal to 4 micrograms/ml. Some endemic differences in patterns of SM-7338 activity against selected gram-negative species were found among some medical centers.
PMCID: PMC172479  PMID: 2658796
23.  Antimicrobial activity, spectrum, and recommendations for disk diffusion susceptibility testing of ceftibuten (7432-S; SCH 39720), a new orally administered cephalosporin. 
Antimicrobial Agents and Chemotherapy  1988;32(10):1576-1582.
The antimicrobial activity and spectrum of ceftibuten (7432-S; SCH 39720) was determined on a wide variety of bacterial species selected for resistance to oral and parenteral beta-lactam antimicrobial agents. Ceftibuten was found to be the most active beta-lactam tested against members of the family Enterobacteriaceae, inhibiting 81.6% of strains at less than or equal to 8.0 micrograms/ml compared with 75.0 and 54.8% of strains inhibited by cefixime and cefuroxime, respectively. All strains of Haemophilus influenzae (MIC for 90% of strains [MIC90], less than or equal to 0.06 microgram/ml), Branhamella catarrhalis (MIC90, 3.0 micrograms/ml), and pathogenic Neisseria spp. (MIC90, less than or equal to 0.06 and 0.019 microgram/ml) were susceptible to ceftibuten. Beta-hemolytic Streptococcus spp. (serogroups A, B, C, and G) were also inhibited by ceftibuten, but penicillin-resistant pneumococci were generally resistant to cefixime and ceftibuten. The activity and spectrum of ceftibuten seem most applicable to infections of the respiratory and urinary tract plus those infections caused by pathogenic Neisseria spp. Ceftibuten disks (30 micrograms) were evaluated and found to have an acceptable correlation (r = 0.88) with ceftibuten MICs. Preliminary zone size interpretive criteria for MIC breakpoints of less than or equal to 4.0 and less than or equal to 8.0 micrograms/ml were calculated.
PMCID: PMC175922  PMID: 3190185
24.  In vitro activities of azithromycin (CP 62,993), clarithromycin (A-56268; TE-031), erythromycin, roxithromycin, and clindamycin. 
The in vitro activity of azithromycin (CP 62,993 or XZ-450) against Haemophilus influenzae was greater than that of three other macrolides. However, azithromycin was four- to eightfold less active than erythromycin against the gram-positive cocci and against Listeria monocytogenes. Erythromycin and azithromycin were similar in their activity against Legionella pneumophila, Neisseria gonorrhoeae, Neisseria meningitidis, and Branhamella catarrhalis.
PMCID: PMC172265  PMID: 2840016
25.  Antimicrobial activity and disk diffusion susceptibility testing of U-76,253A (R-3746), the active metabolite of the new cephalosporin ester, U-76,252 (CS-807). 
Compound U-76,253A (R-3746), the active metabolite sodium salt of the prodrug ester U-76,252 (CS-807), was demonstrated to be active against members of the family Enterobacteriaceae with 82 and 85% of strains inhibited by less than or equal to 2.0 and less than or equal to 4.0 micrograms/ml, respectively. In addition, U-76,253A inhibited all strains of Branhamella catarrhalis, Haemophilus influenzae, pathogenic Neisseria spp., oxacillin-susceptible Staphylococcus aureus, beta-hemolytic streptococci, and pneumococci at less than or equal to 4.0 micrograms/ml. Pseudomonas spp., Acinetobacter spp., enterococci, and oxacillin-resistant staphylococci were resistant to U-76,253A. This U-76,253A antimicrobial activity and spectrum was generally superior to that of comparison orally administered cephems (cefaclor, cefuroxime, and cefixime) and the amoxicillin-clavulanic acid combination. Tests with beta-lactamase-producing isolates indicated that U-76,253A was bactericidal and that its MICs were only influenced by high inoculum concentrations (10(7) CFU/ml) against type Ia and IVc enzyme-producing strains. Preliminary disk diffusion interpretive zone criteria were calculated for 10- and 30-micrograms U-76,253A disks and several possible susceptible MIC breakpoints. The absolute interpretive agreement between MICs and zone diameters ranged from 87.8 to 95.6%. Final selection of interpretive criteria awaits further U-76,252 pharmacokinetic information.
PMCID: PMC172198  PMID: 3377457

Results 1-25 (59)