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1.  Mezlocillin: tentative interpretive standards for disk diffusion susceptibility testing. 
The susceptibility of 447 clinical bacterial isolates to mezlocillin and carbenicillin was tested by standardized agar disk diffusion and reference broth micro-dilution methods. Tentative interpretive criteria for disk susceptibility testing by using 75 micrograms mezlocillin disks are proposed: susceptible, greater than or equal to 16 mm; indeterminate, 13 to 15 mm; and resistant, less than or equal to 12 mm. These would be applicable to both Pseudomonas species and the Enterobacteriaceae, but not to Staphylococcus aureus. For S. aureus, the breakpoints for susceptible, greater than or equal to 29 mm, and resistant, less than or equal to 28 mm, hold for mezlocillin as well as for the other penicillinase-susceptible penicillins.
PMCID: PMC181663  PMID: 6456689
2.  Tentative interpretive criteria for the diffusion susceptibility test using 30-microgram netilmicin disks. 
The disk diffusion inhibitory zone diameters for 10-microgram and 30-microgram netilmicin disks were correlated with minimum inhibitory concentrations against 471 clinical strains tested in cation-supplemented Mueller-Hinton broth. Regression line and error-rate bounded analysis favored the use of 30-microgram netilmicin disks utilizing zone size breakpoints of greater than or equal to 17 mm to indicate susceptibility (less than or equal to 8 microgram/ml) and less than or equal to 13 mm to indicate resistance (greater than 32 microgram/ml). Significant minor interpretive errors may be expected when testing populations of Pseudomonas that have netilmicin minimum inhibitory concentrations near the intermediate range (16 microgram/ml).
PMCID: PMC284029  PMID: 7425615
3.  Moxalactam (LY127935), a new semisynthetic 1-oxa-beta-lactam antibiotic with remarkable antimicrobial activity: in vitro comparison with cefamandole and tobramycin. 
Moxalactam (LY127935) exhibited greater in vitro activity than cefamandole and tobramycin against clinical isolates of Enterobacteriaceae, Aeromonas hydrophila, and Pseudomonas maltophilia. The activities of the three drugs against other microorganisms were as follows: for staphylococci, cefamandole = tobramycin greater than moxalactam; for streptococci, cefamandole greater than moxalactam greater than tobramycin; and for Pseudomonas aeruginosa, tobramycin greater than moxalactam greater than cefamandole. Moxalactam also demonstrated significant activity against the Bacteroides fragilis group and other anaerobes. Moxalactam was comparable to cefotaxime (HR756) in its inhibition of cephalothin-resistant and aminoglycoside-resistant clinical isolates.
PMCID: PMC283866  PMID: 6446880
4.  In vitro activity of a new macrolide, A-56268, compared with that of roxithromycin, erythromycin, and clindamycin. 
A new macrolide (A-56268) was found to be approximately twice as active as erythromycin and four to eight times more active than roxithromycin. All three macrolides were similar in their potency against anaerobes. Human plasma enhanced the antistaphylococcal activity of A-56268 and erythromycin but reduced the activities of roxithromycin and clindamycin.
PMCID: PMC174723  PMID: 2952064
5.  Tentative interpretive standards for disk susceptibility tests with moxalactam (LY127935). 
Moxalactam (LY127935; 6059-S) is a new beta-lactam antibiotic. We propose tentative zone standards for agar diffusion susceptibility tests with 30-microgram disks. The final selection of minimal inhibitory concentration breakpoints for definition of resistant and susceptible categories must await clinical experience with this drug. Some of the clinical questions to be answered are defined. A moderately susceptible (intermediate) category is proposed for those strains with minimal inhibitory concentrations of 16 or 32 microgram/ml (zones 15 to 22 mm in diameter). Strains with minimal inhibitory concentrations of greater than or equal to 64 microgram/ml are considered resistant, and those with minimal inhibitory concentrations of less than or equal to 8 microgram/ml are considered susceptible. Tests with 30-microgram disks did not satisfactorily separate strains with minimal inhibitory concentrations of 8 microgram/ml from strains requiring < 2 microgram/ml for inhibition, because the regression line became parabolic at concentrations of 2 microgram/ml and below. However, the disk tests were satisfactory for categorizing isolates into the above-described susceptible, moderately susceptible (intermediate), and resistant categories.
PMCID: PMC284081  PMID: 6449905
6.  Susceptibilities of beta-lactamase-producing and -nonproducing ampicillin-resistant strains of Haemophilus influenzae to ceftibuten, cefaclor, cefuroxime, cefixime, cefotaxime, and amoxicillin-clavulanic acid. 
In in vitro studies we evaluated the susceptibilities of beta-lactamase-producing and -nonproducing, ampicillin-resistant strains of Haemophilus influenzae and compared them with those of ampicillin-susceptible strains. Ampicillin, amoxicillin-clavulanic acid, ceftibuten, cefaclor, cefuroxime, cefixime, and cefotaxime were evaluated by broth microdilution tests and disk diffusion tests. The disk diffusion tests accurately categorized beta-lactamase-producing strains and ampicillin-susceptible strains as being susceptible to the study drugs other than ampicillin. Ampicillin-resistant, beta-lactamase-nonproducing strains were relatively resistant to all seven study drugs, but the disk diffusion test did not always predict that resistance. The clinical relevance of the decreased susceptibility to various agents remains unclear, but to be conservative, all ampicillin-resistant, beta-lactamase-nonproducing strains might be assumed to be resistant to other beta-lactams. After excluding that small group of isolates, reliable susceptibility test results were obtained with lots of Haemophilus Test Medium that met quality assurance criteria.
PMCID: PMC187597  PMID: 8431012
7.  In vitro activity of apalcillin compared with those of piperacillin and carbenicillin against 6,797 bacterial isolates from four separate medical centers. 
Quantitative susceptibility tests were performed in four separate medical centers, in which apalcillin was compared with piperacillin and carbenicillin. Data from tests of 6,797 isolates confirmed that apalcillin and piperacillin had nearly identical spectra of activity but that apalcillin was significantly more active against Pseudomonas aeruginosa (MIC required to inhibit 90% of strains, 2.0 versus 64 micrograms/ml) and Acinetobacter calcoaceticus subsp. anitratus (MIC required to inhibit 90% of strains, 2.0 versus 16 micrograms/ml). Against 166 anaerobic bacterial isolates, apalcillin demonstrated in vitro activity.
PMCID: PMC185614  PMID: 6732234
8.  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
9.  In vitro inactivation of aminoglycosides by sulbactam, other beta-lactams, and sulbactam-beta-lactam combinations. 
At clinically achievable levels (e.g., 25 micrograms/ml), sulbactam exerted no effect on aminoglycoside concentrations when incubated together in pooled serum at 37 degrees C for up to 24 h. Sulbactam alone and in combination with ampicillin or cefoperazone inactivated tobramycin, gentamicin, netilmicin, and amikacin in vitro when the sulbactam concentration was 200 to 225 micrograms/ml. At 75 micrograms/ml, sulbactam inactivated only tobramycin. Inactivation of tobramycin by high concentrations of sulbactam occurred even at -20 degrees C, but not at -70 degrees C, and was influenced by the serum matrix.
PMCID: PMC244964  PMID: 2014975
10.  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
11.  Cross-resistance among cinoxacin, ciprofloxacin, DJ-6783, enoxacin, nalidixic acid, norfloxacin, and oxolinic acid after in vitro selection of resistant populations. 
Six different gram-negative bacilli were serially transferred through subinhibitory concentrations of seven quinolone derivatives or related organic acids. A gradual, stepwise decrease in susceptibility was noted with all seven drugs, and the resistant cultures demonstrated a concomitant cross-resistance to the other drugs.
PMCID: PMC185641  PMID: 6234858
12.  In vitro activity of ticarcillin plus clavulanic acid against 632 clinical isolates. 
A total of 632 clinical bacterial isolates were tested for susceptibility to twofold dilutions of ticarcillin alone and in combination with 1, 2, and 4 micrograms of clavulanic acid (CA) (Timentin) per ml by a reference microdilution method. With the addition of CA, ticarcillin MICs were reduced eightfold or greater with 54 of 59 (92%) strains of the family Enterobacteriaceae with ticarcillin MICs of greater than or equal to 64 micrograms/ml. The inhibitory effect of CA on pseudomonads was minimal. Ticarcillin MICs for beta-lactamase-producing Haemophilus influenzae, Neisseria gonorrhoeae, and most Staphylococcus aureus were reduced to less than or equal to 0.5 micrograms/ml when CA was added. For dilution susceptibility testing of ticarcillin-clavulanic acid, dilutions of ticarcillin combined with 2 micrograms of CA per ml is suggested.
PMCID: PMC185529  PMID: 6721472
13.  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
14.  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
15.  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
16.  Antimicrobial activity of Ro 15-8074, active metabolite of a new oral cephalosporin (Ro 15-8075), against 7,775 recent clinical isolates. 
Susceptibility testing of 7,775 recent clinical isolates from four medical centers showed Ro 15-8074 to be 2-to greater than 8-fold more active than either cefaclor or cefuroxime against the Enterobacteriaceae. Ro 15-8074 MICs for 50% of the strains tested were greater than or equal to 32 micrograms/ml for Staphylococcus spp., enterococci, Pseudomonas aeruginosa, and Pseudomonas maltophilia. beta-Lactamase hydrolysis experiments failed to demonstrate significant Ro 15-8074 inactivation by commonly encountered chromosomal or plasmid-mediated enzymes (P99, K1, K14, TEM, and CARB).
PMCID: PMC180632  PMID: 3492961
17.  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
18.  Interpretive standards for disk susceptibility tests with Sch 21420 and amikacin. 
Disk susceptibility tests with two structurally related aminoglycosides (amikacin and Sch 21420) were evaluated. Tests with 10- and 30-micrograms amikacin disks confirmed previous recommendations for interpretive zone standards; 30-micrograms disks are preferred. Tests with 10-, 20-, and 30-micrograms Sch 21420 disks led to similar conclusions. The 30-micrograms Sch 21420 disks are recommended, with zone standards of less than or equal to 14 mm for the resistant category (minimal inhibitory concentration, greater than or equal to 32 micrograms/ml) and greater than or equal to 17 mm for the susceptible category (minimal inhibitory concentration, less than or equal to 16 micrograms/ml). If a minimal inhibitory concentration breakpoint of less than or equal to 8 micrograms/ml is preferred for defining the susceptible category, somewhat different zone standards may be used (less than or equal to 15 mm and greater than or equal to 19mm). Further evaluation documented the fact that tests with 30-micrograms amikacin disks predicted resistance or susceptibility to Sch 21420 almost as well as did a 30-micrograms Sch 21420 disk. Thus, the class concept of disk testing was judged to applicable, and routine testing with Sch 21420 may not be required.
PMCID: PMC284059  PMID: 7447420
19.  Cefotaxime: in vitro activity and tentative interpretive standards for disk susceptibility testing. 
Tested against 9,412 recent clinical isolates, cefotaxime exhibited 8 to 64 times greater activity against the Enterobacteriaceae than did cephalothin and two to four times greater activity against Pseudomonas aeruginosa, but only one-half to one-eighth the activity of cephalothin against staphylococci. Using 420 different clinical isolates, but with comparable minimal inhibitory concentration (MIC) distributions, disk diffusion-MIC regression analyses were performed, using 5- and 30-micrograms cefotaxime disks. Cefotaxime MIC susceptible and resistant breakpoints of less than or equal to 8 and greater than 32 micrograms/ml are tentatively proposed. Based on the MIC breakpoints, the data showed the best discrimination among the three susceptibility categories (susceptible, indeterminate, and resistant) when the 30-micrograms cefotaxime disk was used. The zone diameter breakpoints as determined by the error rate-bounded method and regression analysis were greater than or equal to 23 mm for susceptible, 15 to 22 mm for indeterminate, and less than or equal to 14 mm for resistant.
PMCID: PMC283944  PMID: 6251750
20.  Multicenter evaluation of the in vitro activities of three new quinolones, sparfloxacin, CI-960, and PD 131,628, compared with the activity of ciprofloxacin against 5,252 clinical bacterial isolates. 
The in vitro activities of three new quinolones (sparfloxacin, CI-960, and PD 131,628) were compared with that of ciprofloxacin against 5,252 routine clinical aerobic and facultatively anaerobic bacterial isolates. Overall, CI-960 was the most active drug in vitro (MIC for 90% of the strains tested, 0.13 micrograms/ml); ciprofloxacin and sparfloxacin were the least active (MIC for 90% of the strains tested, 1.0 micrograms/ml). All three new quinolones, but particularly CI-960 and PD 131,628, exhibited significantly greater activity than ciprofloxacin against enterococci and staphylococci.
PMCID: PMC245095  PMID: 2069384
21.  In vitro activities of ampicillin-sulbactam and cefoperazone-sulbactam against oxacillin-susceptible and oxacillin-resistant staphylococci. 
Ampicillin-sulbactam and cefoperazone-sulbactam were tested against staphylococci that were collected from 40 different medical centers throughout the United States. Oxacillin-resistant strains were resistant to both drug combinations, but oxacillin-susceptible strains were uniformly susceptible. The latter included strains with borderline susceptibility to oxacillin and methicillin.
PMCID: PMC171941  PMID: 2285302
22.  In vitro antimicrobial activity of tigemonam, a new orally administered monobactam. 
At five geographically separate medical centers, over 6,000 clinical bacterial isolates were tested for their susceptibility to tigemonam by the broth microdilution method. The antimicrobial spectrum of tigemonam was similar to that of aztreonam, but with two differences. Aztreonam was more active against Pseudomonas spp., and tigemonam was more active against some streptococci. Tigemonam was highly resistant to hydrolysis by the eight beta-lactamase enzymes tested. A significant (greater than a fourfold increase in the MICs of tigemonam) inoculum effect occurred when 3 of 13 isolates were tested with inocula of 5 X 10(5) and 1 X 10(7) CFU/ml. Tigemonam was bactericidal for all but 1 of the 13 isolates. Of the four quality-control strains recommended by the National Committee for Clinical Laboratory Standards, only Escherichia coli ATCC 25922 provided on-scale results. The proposed MIC quality-control range of tigemonam for E. coli ATCC 25922 is 0.13 to 0.5 micrograms/ml.
PMCID: PMC172173  PMID: 3259122
23.  Antimicrobial activity of ceftriaxone, cefotaxime, desacetylcefotaxime, and cefotaxime-desacetylcefotaxime in the presence of human serum. 
Eighty-seven organisms were tested against ceftriaxone, cefotaxime, desacetylcefotaxime, and the combination of cefotaxime and desacetylcefotaxime (1:1 ratio) in broth containing 0, 25, or 50% human serum. In the presence of human serum, ceftriaxone MICs were four- to eightfold higher than those obtained in broth, changing 98% of Staphylococcus aureus strains from the susceptible to the moderately susceptible category and 53% of selected gram-negative strains to a more resistant category. The MICs of cefotaxime, desacetylcefotaxime, and cefotaxime plus desacetylcefotaxime were not adversely affected by human serum; in fact, the bactericidal activity was slightly improved.
PMCID: PMC174842  PMID: 3606081
24.  Antistaphylococcal activity of ceforanide and cefonicid in the presence of human serum. 
Tests with 52 strains of Staphylococcus aureus compared ceforanide and cefonicid. Addition of 50% human serum to the test system reduced the bacteriostatic and bactericidal activities of cefonicid, but ceforanide was not affected as greatly.
PMCID: PMC180380  PMID: 3729326
25.  Antimicrobial activity and other in vitro properties of cefoperazone A, the principal metabolite of cefoperazone sodium. 
Cefoperazone A, the principal metabolite of cefoperazone, was found to have an antimicrobial activity ranging from slightly below to 16-fold less than that of the parent drug. Like cefoperazone, the metabolite is bactericidal, penetrates well into bacterial cells, and has moderate beta-lactamase stability, some strains of members of the family Enterobacteriaceae produce an inoculum effect on the metabolite activity.
PMCID: PMC185156  PMID: 6638991

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