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1.  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
2.  Patterns and mechanisms of beta-lactam resistance among isolates of Escherichia coli from hospitals in the United States. 
To study the national distribution of beta-lactam resistance patterns and mechanisms among Escherichia coli organisms isolated in U.S. hospitals, 652 ampicillin-resistant (Am(r)) or ampicillin-intermediate (Ami) isolates were submitted to the Centers for Disease Control from March 1983 through July 1984 by nine hospitals participating in the National Nosocomial Infections Study. Among the isolates (most of which caused urinary tract infections), 78% were Am(r) and 22% were Ami by the interpretative criteria established by the National Committee for Clinical Laboratory Standards. Resistance to carboxypenicillins ranged from 73 to 74%, and that to acylureidopenicillins ranged from 43 to 66%. A total of 26% of the isolates were resistant to cephalothin, and 4% were resistant to cefazolin. Resistance to cefoxitin was 1%, while resistances to cefuroxime and cefamandole were 2 and 7%, respectively. With the exception of cefsulodin (98% resistant) and cefoperazone (1% resistant), there was no resistance to newer cephalosporins or aztreonam. In general, only minor differences in the incidence of resistance to beta-lactam antibiotics were noted in hospital-acquired versus non-hospital-acquired isolates as well as among isolates from various regions of the United States. TEM beta-lactamases were produced by 87% of the 237 Am(r) isolates examined. By our methods, OXA and chromosomal (type I) beta-lactamases were detected in 2 and 28 isolates, respectively, and plasmid-mediated extended-spectrum cephalosporinases were detected in none of the isolates. Disk substrate and clavulanic acid inhibition assays revealed that TEM beta-lactamase conferred Am(r) and resistance to carboxypenicillins, acylureidopenicillins, cephalothin, cefamandole, cefsulodin, and cefoperazone. A total of 391 isolates were screened for plasmids, and 259 isolates were examined by DNA hybridization with a TEM probe. Among 462 plasmids probed, 129 plasmids, ranging from 4 to 140 megadaltons, harbored TEM sequences. Although beta-lactam resistance in clinical isolates of E. coli is predominantly mediated by TEM beta-lactamase, the diverse spectrum of resistance appears to be related to additional strain=dependent factors.
PMCID: PMC171683  PMID: 2193616
3.  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
4.  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
5.  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
6.  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
7.  Antimicrobial susceptibility of vancomycin-resistant Leuconostoc, Pediococcus, and Lactobacillus species. 
Eighty-five strains of vancomycin-resistant gram-positive bacteria from three genera, Leuconostoc, Pediococcus, and Lactobacillus, were tested to determine susceptibility to 24 antimicrobial agents by broth microdilution and to 10 agents by disk diffusion. The MICs of vancomycin and teicoplanin ranged from 64 to greater than 512 micrograms/ml; however, the MICs of daptomycin, a new lipopeptide, were all less than or equal to 0.25 micrograms/ml. None of the organisms were resistant to imipenem, minocycline, chloramphenicol, gentamicin, or daptomycin. The MICs of penicillin were in the moderately susceptible range for all but three strains. Susceptibility to the other agents varied by genus and, in some cases, by species. When disk diffusion results were compared with MICs for drugs recommended for streptococci by the National Committee for Clinical Laboratory Standards, Villanova, Pa., few very major or major errors were obtained, but the number of minor errors was 19.3%. Therefore, we recommended that MIC testing be used instead of disk diffusion testing for these organisms.
PMCID: PMC171641  PMID: 2344161
8.  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
9.  Influence of cation supplements on activity of netilmicin against Pseudomonas aeruginosa in vitro and in vivo. 
Antimicrobial Agents and Chemotherapy  1987;31(10):1514-1518.
In vitro studies were performed with 74 Pseudomonas aeruginosa isolates which were collected during a multicenter trial. The isolates were obtained from 70 patients who had been treated with netilmicin as the only antipseudomonal antibiotic. Clinically, 83% of the patients were cured or improved, and 64% of the Pseudomonas isolates were eliminated by chemotherapy. The 74 clinical isolates and 38 additional isolates with known mechanisms of aminoglycoside resistance were tested in three separate laboratories by disk diffusion methods and by microdilution tests with three broth media (Mueller-Hinton broth with full, half, and no cation supplements). Isolates that responded to netilmicin therapy and those that failed to respond were all susceptible by the disk test, and most were susceptible by microdilution tests with unsupplemented broth. However, over half of the clinical isolates appeared to be resistant when cations were added to the broth medium. Strains capable of producing enzymes that inactivate netilmicin were resistant by all methods tested. Broth dilution and agar dilution results were most comparable when half of the recommended cation supplements was added to Mueller-Hinton broth. Further consideration should be given to reducing the concentration of cations that are added to Mueller-Hinton broth when netilmicin susceptibility tests are being performed. However, additional studies with other aminoglycosides are needed before appropriate testing conditions can be standardized.
PMCID: PMC174981  PMID: 3124731
10.  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
11.  Microplate phosphocellulose binding assay for aminoglycoside-modifying enzymes. 
We modified the phosphocellulose binding assay for aminoglycoside-modifying enzymes (AMEs) by use of microdilution plates and a multichannel micropipette. Batteries of aminoglycoside substrates for screening organisms for the presence of AMEs as well as for subclassifying enzymes were prepared and stored in microdilution plates. When tested in parallel with the conventional tube reaction assay, the microplate assay yielded comparable radioactive counts and therefore equally correct identifications of AMEs in 32 isolates representing nine bacterial species. Other modifications, such as multichannel dispensing of crude enzyme preparations and radioisotopic precursors, provided a more rapid, convenient, and less expensive means of examining large collections of organisms for AMEs.
PMCID: PMC180612  PMID: 3028252
12.  In vitro evaluation of A-56619 and A-56620, two new quinolones. 
The in vitro activities of two new aryl-fluoroquinolones (A-56619 and A-56620) were compared with those of ciprofloxacin, ofloxacin, enoxacin, and norfloxacin. All six quinolones had broad spectra of antibacterial activity; the streptococci, Pseudomonas maltophilia, and Pseudomonas cepacia were the least susceptible. A-56619, A-56620, and chloramphenicol had similar activity against anaerobic bacteria. With both drugs, a low frequency of resistant variants (less than 10(-8)) was observed. By regression analysis, A-56619 MICs correlated best with ofloxacin MICs and A-56620 was most similar to ciprofloxacin.
PMCID: PMC180360  PMID: 2942099
13.  Antimicrobial susceptibility of five subgroups of Mycobacterium fortuitum and Mycobacterium chelonae. 
Broth microdilution MICs were determined for 258 clinical isolates of Mycobacterium fortuitum (3 biovariants) and M. chelonae (2 subspecies) with amikacin, tobramycin, cefoxitin, doxycycline, erythromycin, and sulfamethoxazole-trimethoprim and with several new beta-lactams and aminoglycosides and ciprofloxacin. Variations in susceptibility by and within species subgroups confirm the need for susceptibility testing against clinically important strains.
PMCID: PMC180333  PMID: 4083863
14.  Antibacterial activities of ciprofloxacin, norfloxacin, oxolinic acid, cinoxacin, and nalidixic acid. 
In vitro studies were performed comparing ciprofloxacin (Bay o 9867) and norfloxacin with three related organic acids. Ciprofloxacin was two to eight times more active than norfloxacin against 658 bacterial isolates representing 30 species. For all species tested, ciprofloxacin MICs for 90% inhibition were less than or equal to 2.0 micrograms ml. Additional tests with 5,994 isolates detected only 37 (0.6%) strains resistant to 2.0 micrograms of ciprofloxacin per ml and 106 (1.8%) resistant to 1.0 micrograms/ml. Only 6 (0.1%) of the 5,994 strains were resistant to 16 micrograms of norfloxacin per ml, and 129 (2.1%) were resistant to 4.0 micrograms/ml. The majority of resistant strains were streptococci or Pseudomonas spp. Resistance among the Enterobacteriaceae was extremely rare (i.e., greater than 99.8% susceptible to both drugs.
PMCID: PMC185603  PMID: 6233935
15.  Cefotetan, a new cephamycin: comparison of in vitro antimicrobial activity with other cephems, beta-lactamase stability, and preliminary recommendations for disk diffusion testing. 
Cefotetan is a new, potent, 7 alpha-methoxy cephalosporin (cephamycin). The in vitro activity of cefotetan tested in a multiphasic, collaborative study against 12,260 consecutive clinical isolates and 448 selected isolates showed 93% of Enterobacteriaceae, 90% of methicillin-susceptible Staphylococcus aureus (broth dilution), 83% of Bacteroides fragilis, and 72% of non-enterococcal streptococci to be inhibited by less than or equal to 8 micrograms/ml. Beta-Lactamase-producing and -nonproducing Haemophilus influenzae strains were inhibited by less than or equal to 1.0 micrograms/ml. Cefotetan's inhibitory spectrum paralleled those of the newest generation of cephems and exceeded those of cefoxitin and cefamandole. No useful activity was present against Streptococcus faecalis or Pseudomonas aeruginosa. Cefotetan was bactericidal without significant inoculum effect and was highly resistant to hydrolysis by Richmond-Sykes types I, III, and IV beta-lactamases. Hydrolysis of the chromogenic cephalosporin PADAC (pyridine-2-azo-p-dimethylaniline cephalosporin) by type I beta-lactamases was markedly inhibited by concentrations of cefotetan similar to those of the potent inhibitor dicloxacillin. Analysis of agar disk diffusion for several disk potencies and broth dilution susceptibility tests by regression and error rate-bounding methods produced preliminary tentative zone standards (30-micrograms disk, using minimal inhibitory concentration breakpoints of less than or equal to 8 micrograms/ml susceptible and greater than 32 micrograms/ml resistant, or 75-micrograms disk, using minimal inhibitory concentration breakpoints of less than or equal to 16 micrograms/ml susceptible and greater than or equal to 64 micrograms/ml resistant) of greater than or equal to 18 mm susceptible, less than or equal to 14 mm resistant, and 15 to 17 mm indeterminate. Staphylococcus aureus testing with the 30-micrograms disk is not recommended.
PMCID: PMC185673  PMID: 6983862
16.  Rapidly growing mycobacteria: testing of susceptibility to 34 antimicrobial agents by broth microdilution. 
A total of 18 strains of Mycobacterium fortuitum, 15 strains of M. chelonei, and 31 strains of M. chelonei-like organisms were tested by both broth microdilution and agar dilution to determine their susceptibility to 34 antimicrobial agents. All strains grew well enough in cation-supplemented Mueller-Hinton broth for endpoints to be read after 72 h of incubation. Some strains of M. chelonei did not grow on Mueller-Hinton agar. A few discrepancies were noted between the broth and agar procedures. For M. fortuitum, doxycycline, minocycline, amikacin, sulfamethoxazole, and sulfamethoxazole-trimethoprim were the most active agents. For M. chelonei, amikacin, sisomicin, tobramycin, and erythromycin were the most active agents. The M. chelonei-like organisms were most susceptible to ampicillin, doxycycline, minocycline, amikacin, erythromycin, sulfamethoxazole, and sulfamethoxazole-trimethoprim. Broth microdilution appears to be a reliable method for susceptibility testing of rapidly growing mycobacteria, although clinical studies are needed to determine how well in vitro results correlate with therapeutic in vivo outcome.
PMCID: PMC183707  PMID: 6927280
17.  Cefsulodin: antibacterial activity and tentative interpretive zone standards for the disk susceptibility test. 
Cefsulodin (SCE-129) is a cephalosporin with a spectrum of antibacterial activity largely limited to Pseudomonas aeruginosa and Staphylococcus aureus. Cefsulodin was compared with carbenicillin, ticarcillin, mezlocillin, and piperacillin against 779 nonenteric gram-negative bacilli and staphylococci collected from five geographically separate institutions. Against P. aeruginosa, cefsulodin was somewhat more active than piperacillin and much more active than other penicillins. In addition, cefsulodin was active against penicillinase-producing strains of S. aureus. Collaborative efforts in three laboratories led to the following tentative zone size breakpoints for 30-micrograms cefsulodin disks: susceptible greater than or equal to 18 mm (minimal inhibitory concentration) [MIC] less than or equal to 16 micrograms/ml) and resistant less than or equal to 14 mm (MIC greater than or equal to 64 micrograms/ml). These zone standards are still tentative since the dosage schedule has not yet been defined and sufficient clinical experience has not yet been gathered to support the validity of these MIC breakpoints.
PMCID: PMC181736  PMID: 6211134
18.  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
19.  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
20.  In vitro antimicrobial activity of cefoperazone, cefotaxime, moxalactam (LY127935), azlocillin, mezlocillin, and other beta-lactam antibiotics against Neisseria gonorrhoeae and Haemophilus influenzae, including beta-lactamase-producing strains. 
Minimum inhibitory concentrations and agar disk diffusion tests were determined on clinical isolates of beta-lactamase-positive and beta-lactamase-negative Neisseria gonorrhoeae and Haemophilus influenzae with the newer beta-lactam antibiotics, cefoperazone, cefotaxime, moxalactam (LY127935), azlocillin, mezlocillin, and piperacillin, and with seven older beta-lactam antibiotics. All the drugs were active against beta-lactamase-negative strains of N. gonorrhoeae and H. influenzae. The drug most active against beta-lactamase-positive N. gonorrhoeae was cefotaxime, followed closely by cefoperazone, moxalactam, piperacillin, and mezlocillin. The drugs most active against beta-lactamase-positive strains of H. influenzae were cefotaxime, moxalactam, cefoperazone, and cefamandole.
PMCID: PMC283867  PMID: 6249195
21.  Sulfamethoxazole-trimethoprim synergism for Neisseria gonorrhoeae. 
Sulfamethoxazole and trimethoprim are synergistic against many bacteria in sulfamethoxazole/trimethoprim concentrations of 20:1, but single-dose therapy of gonorrhea with the combination is disappointing. We used agar dilution techniques to determine minimal inhibitory concentrations of sulfamethoxazole and trimethoprim for 168 gonococci isolated from men with acute urethritis in Atlanta, Ga. The geometric mean minimal inhibitory concentrations were 5.6 microgram of sulfamethoxazole per ml and 24.3 microgram of trimethoprim per ml, a ratio of 1:4. The concentration of sulfamethoxazole inhibiting 50% of gonococcal strains dropped only from 4.7 microgram/ml to 2.9 microgram/ml with the addition of a 1/20 dilution of trimethoprim. We studied synergism with various ratios of sulfamethoxazole to trimethoprim against 20 random strains. A ratio of 1:1 was always synergistic and was the most synergistic ratio for 15 strains, whereas the 19:1 ratio was never the most syngergistic. The 19:1 ratio failed to show synergism against seven strains, but showed antagonism at this ratio with five of these seven. The sulfamethoxazole/trimethoprim ratio of 19:1 usually achieved in serum after oral administration is minimally syngergistic and is sometimes antagonistic for gonococci.
PMCID: PMC283765  PMID: 6770754
22.  Activity of pirlimycin against pathogens from cows with mastitis and recommendations for disk diffusion tests. 
Pirlimycin is an analog of clindamycin that will be recommended for therapy of bovine mastitis. It has good activity against staphylococci and streptococci, the major pathogens for bovine mastitis. Five hundred and thirty bacterial isolates recovered from cows with mastitis were studied to confirm the spectrum of activity and to develop recommendations for susceptibility testing. Pirlimycin is not active against isolates of Enterobacteriaceae, it varies in its activity against enterococci, and it is active against veterinary isolates of streptococci (MIC for 50% of strains tested, < or = 0.03 to 0.06 microgram/ml) and staphylococci (MIC for 50% of strains tested, 0.25 to 1.0 microgram/ml). On the basis of levels of drug attained in the milk with recommended dosing schedules, we chose MIC breakpoints of < or = 2 micrograms/ml for susceptibility and > or = 4 micrograms/ml for resistance. We also recommended a disk diffusion test using a disk containing 2 micrograms/ml and breakpoints of < or = 12 mm for resistance and > or = 13 mm for susceptibility.
PMCID: PMC187914  PMID: 8517701
23.  National collaborative study of the prevalence of antimicrobial resistance among clinical isolates of Haemophilus influenzae. 
A total of 2,811 clinical isolates of Haemophilus influenzae were obtained during 1986 from 30 medical centers and one nationwide private independent laboratory in the United States. Among these, 757 (26.9%) were type b strains. The overall rate of beta-lactamase-mediated ampicillin resistance was 20.0%. Type b strains were approximately twice as likely as non-type b strains to produce beta-lactamase (31.7 versus 15.6%). The MICs of 12 antimicrobial agents were determined for all isolates. Ampicillin resistance among strains that lacked beta-lactamase activity was extremely uncommon (0.1%). Percentages of study isolates susceptible to cefamandole, cefaclor, cephalothin, and cephalexin were 98.7, 94.5, 87.3, and 43.3%, respectively. For 14 strains (0.5% of the total), chloramphenicol MICs were greater than or equal to 8.0 micrograms, and thus the strains were considered resistant. All of these resistant strains produced chloramphenicol acetyltransferase. In addition, all 14 strains were resistant to tetracycline; 11 produced beta-lactamase. The percentage of isolates susceptible to tetracycline was 97.7%. In contrast, erythromycin and sulfisoxazole were relatively inactive. The combination of erythromycin-sulfisoxazole (1/64) was more active than erythromycin alone but essentially equivalent in activity to sulfisoxazole alone. Finally, small numbers of clinical isolates of H. influenzae were resistant to trimethoprim-sulfamethoxazole and rifampin.
PMCID: PMC172131  PMID: 3259121
24.  A gene probe for TEM type beta-lactamases. 
A restriction fragment of plasmid pBR322 bearing the TEM-1 beta-lactamase structural gene was electroeluted from agarose gels after digestion with EcoRI and HinfI. The 1-kilobase fragment was 32P-labeled and used to examine genetic relationships with nucleic acids encoding seven other beta-lactamase classes. The probe hybridized only with TEM-2 and OXA-2 class plasmids.
PMCID: PMC176331  PMID: 3876073
25.  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

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