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The in vitro activity of cefazaflur, a parenteral cephalosporin, was determined against 590 clinical isolates. Cefazaflur inhibited the majority of gram-positive cocci at concentrations below 1 μg/ml except for enterococci. The agent was as active as cefamandole or cefoxitin against most Escherichia coli, Klebsiella pneumoniae , and Proteus mirabilis . Although it inhibited a number of strains of Enterobacter , indole-positive Proteus , and Serratia resistant to cephalothin, it was much less active against these organisms than were cefamandole or cefoxitin.

The purified cephalosporinase from Proteus vulgaris hydrolyzed a variety of cephalosporins, including cefuroxime, at a high level; its activity was inhibited by clavulanic acid.

Thienamycin was shown to be a more potent inhibitor than ampicillin of the enzyme peptidoglycan transpeptidase from Escherichia coli .

Microdilution and broth dilution techniques were compared for the susceptibility testing of 50 clinical yeast isolates to 5-fluorocytosine and amphotericin B. Good correlation between methods was obtained with all isolates except Cryptococcus neoformans .

An accurate, plate diffusion bioassay for ticarcillin, utilizing the fast-replicating Beneckea natriegens and 4% salt agar, is described in this report. Zones of inhibition were well defined after 3 h, and the limit of sensitivity was around 5.0 μg/ml. The assay is simple to carry out, and duplicate assays can be performed on as little as 40 μl of serum.

The in vivo activities of cefsulodin, sulbenicillin, and gentamicin were compared in mice infected intraperitoneally with Pseudomonas aeruginosa . In mice infected with sulbenicillin- and gentamicin-susceptible strains, cefsulodin was about 12 to 60 times more active than sulbenicillin and had an activity similar to gentamicin. In mice, the activity of cefsulodin was independent whether the strains were resistant to gentamicin or not, but it was considerably affected by resistance of the strains to sulbenicillin.

Twenty strains of Staphylococcus aureus isolated from patients with endocarditis were examined in vitro for susceptibility to rifampin, nafcillin, and vancomycin and to combinations of rifampin with nafcillin or vancomycin. Minimum bactericidal concentrations of rifampin ranged from 0.0031 to 0.0125 μg/ml, of nafcillin ranged from 0.078 to 0.312 μg/ml, and of vancomycin ranged from 0.312 to 1.25 μg/ml. The combination of rifampin with nafcillin was synergistic for 12 strains; the combination of rifampin plus vancomycin was synergistic for 5 of the isolates.

Fifty strains of Streptococcus mutans , including defined strains and clinical isolates, were tested for susceptibility to 20 different antimicrobial agents. Minimal inhibitory concentrations were determined by a liquid microtiter procedure. Antibiotics that were most effective in concentrations below 0.1 μg/ml included penicillin, ampicillin, erythromycin, cephalothin, and methicillin. Antibiotics effective in concentrations between 0.1 μg and 10 μg/ml included rifampin, lincomycin, thiostrepton, spiromycin, vancomycin, streptolydigan, novobiocin, tetracycline, chloramphenicol, spectinomycin, and gentamicin. Antibiotics effective at higher concentrations ranging from 10 μg/ml to 400 μg/ml included the aminoglycosides kanamycin, neomycin, streptomycin, and kasugamycin. Although most antibiotics exhibited inhibitory effects in a narrow range of concentrations, antibiotics such as tetracycline, thiostrepton, and spiromycin had a 1,000-fold range from the lowest to highest concentrations required for growth inhibition.

Of 21 antimicrobial agents tested in vitro, amikacin was the most predictably active against clinical isolates belonging to the Mycobacterium fortuitum complex; however, only 50% of strains studied were susceptible to clinically attainable concentrations of the drug.

The in vitro susceptibility of 96 isolates of Propionibacterium acnes to 17 antibiotics was determined by utilizing an agar dilution technique. With the exception of the aminoglycosides, these organisms are susceptible to virtually all of the commonly used antimicrobial agents.

Clotrimazole (CTM) has a doubtful future with respect to use in treatment of the systemic mycoses. To assess the potential of CTM in combined drug regimens, antifungal effects of CTM together with 5-fluorocytosine (5-FC) or amphotericin B (AMB) were tested in a synthetic liquid medium against Candida albicans, Candida tropicalis , and Torulopsis glabrata . Viable counts were monitored over a 48-h incubation period. Weak inhibitory concentrations of CTM were tested in combination with levels of 5-FC or AMB that alone produced transient antifungal effects followed by rapid recovery of proliferative capacity. Results were similar for each of the organisms studied. Between 24 and 48 h, when cultures containing 5-FC or AMB alone were in the recovery phase, CTM plus 5-FC and CTM plus AMB continued to markedly suppress cell multiplication. It would appear that weak inhibitory concentrations of CTM can act together with 5-FC or AMB to produce antifungal effects greater than that obtained with either of the latter two drugs alone.

A new assay was developed to determine the concentration of amphotericin B in body fluids. The Bactec radiometric system was used to measure CO 2 production by a test strain, Candida albicans MDA 448, in the presence of amphotericin B. After 5-h incubation, drug concentrations as low as 0.2 μg/ml could be detected. The results are comparable to those of the commonly used agar diffusion assay with Paecilomyces varioti .

Escherichia coli MRE 600 is a colicinogenic bacterium. Its colicinogenic activity may be ascribed mostly to colicin E1, although it produces a small amount of another, as yet unidentified, colicin.

Antagonism, determined by isobolograms constructed from data from combinations of ampicillin and chloramphenicol at or below the minimal inhibitory or bactericidal concentrations, was observed against 13 clinical isolates of meningococcus and against one isolate of pneumococcus. Synergy occurred against six strains of pneumococcus and three of meningococcus. Additive effects were noted against 14 isolates of pneumococcus and 5 of meningococcus. There was no relationship between the minimal inhibitory or bactericidal concentrations for the isolates and the occurrence of antagonistic, additive, or synergistic effects. These data indicate that ampicillin and chloramphenicol may be antagonistic in vitro against some strains of pneumococcus or meningococcus.

The in vitro activity of thienamycin was tested against 135 aerobic and anaerobic bacteria. The compound was highly active against resistant gram-negative bacilli and penicillin-resistant Straphylococcus aureus . The antianaerobic spectrum of the drug seemed to be comparable to that of metronidazole.

The results of this investigation showed that the Autobac could be used to determine the susceptibility of Haemophilus influenzae to ampicillin, chloramphenicol, and tetracycline when eugonic broth was supplemented with 1.5% Fildes enrichment. An excellent correlation was obtained between the susceptibilities as determined by the agar dilution minimal inhibitory concentration method and the Autobac. For ampicillin all H. influenzae isolates with minimal inhibitory concentrations of ≤1 μg/ml had light scattering indexes of ≥0.60. Those isolates with minimal inhibitory concentrations of ≥4 μg/ml had light scattering indexes of ≤0.49. For chloramphenicol and tetracycline all isolates had minimal inhibitory concentrations of ≤1 μg/ml and light scattering indexes of ≥0.71.

We report a radioimmunoassay for the new semisynthetic aminoglycoside netilmicin with a sensitivity of 480 pg per tube and a correlation coefficient of 0.94 between this radioimmunoassay and a microbioassay for measurement of netilmicin in serum.

A multiply drug-resistant strain of Proteus mirabilis was isolated from 14 patients on a surgical service. Antimicrobial susceptibility studies demonstrated that the organism was highly resistant to numerous antibiotics, including gentamicin, tobramycin, and sisomicin. The organism was susceptible in vitro to amikacin but had low-level resistance to netilmicin. In vitro susceptibility studies with combinations of cephalothin with netilmicin and trimethoprim with sulfamethoxazole showed these drugs to be synergistic. Other drug combinations failed to act synergistically.

A new technique for detecting penicillinase production in Haemophilus influenzae and Staphylococcus aureus was compared with the capillary procedure for detecting beta-lactamase and the Bauer-Kirby disk susceptibility procedure. Isolates were classified similarly by all three procedures.

Antiviral antibody and interferon did not prevent in vitro reactivation of herpes simplex virus in latently infected sensory ganglia. Phosphonoacetic acid and 9-β- d -arabinofuranosyladenine blocked reactivation, but this treatment did not eradicate the latent infection.

A bioassay method for the polyene antibiotics nystatin and amphotericin B is proposed based on the measurement of the efflux of rubidium ions from a rubidium-loaded yeast culture challenged with the antibiotics. For this purpose a major proportion of the intracellular K + ions in a Saccharomyces cerevisiae culture has been substituted by Rb + ions. The rubidium leakage is measured by atomic absorption spectrophotometry, and a straight-line, dose-response correlation has been obtained for both antibiotics.

The inhibitory and bactericidal activities of josamycin and rosamicin against 29 clinical isolates of Bacteroides fragilis were compared with those of clindamycin, erythromycin, and metronidazole by a broth dilution technique. Josamycin and rosamicin had similar inhibitory activity to metronidazole and clindamycin. Rosamicin had similar bactericidal activity to clindamycin but was less bactericidal than metronidazole (the most bactericidal agent tested). Josamycin was slightly more bactericidal than erythromycin (the least bactericidal agent tested), but less so than rosamicin and clindamycin.

A new synthetic medium having negligible ultraviolet absorbance is described for growing staphylococci in experiments requiring ultraviolet spectrophotometry of cell-free portions of the culture.

Depending on the hematocrit, duplicate or triplicate determinations of serum amphotericin B concentration may be made on as little as 100 μl of capillary blood obtained by finger prick. In an accurate plate diffusion bioassay, using Paecilomyces varioti as the indicator organism, levels of the drug in the therapeutic range can be determined fast enough for clinicians to modify their next dose.

The activities of cefotaxime, moxalactam, MK 0787 ( N -formimidoyl thienamycin), ampicillin, oxacillin, vancomycin, and clindamycin were compared against gram-positive cocci. MK 0787 was the most active and moxalactam was the least active of these drugs, except against methicillin-resistant Staphylococcus aureus , where vancomycin was most active, and penicillin-resistant pneumococci, where cefotaxime was more active.

R plasmids from chloramphenicol-resistant salmonella from Ontario are shown to belong to the H 2 incompatibility subgroup and to mediate a broad-spectrum, phage inhibition function.

We studied the effect of methadone, alone and in combination with antimicrobial agents, on two strains each of Staphylococcus aureus, Pseudomonas aeruginosa , and Serratia marcescens isolated from blood streams of parenteral drug abusers with bacterial endocarditis. Methadone has its own antibacterial effect, although at supraphysiological concentrations, and is even synergistic with antimicrobial agents against some organisms. Thus, methadone does not interfere with the antibacterial effects of antibiotics in vitro.

The minimal inhibitory concentrations of piperacillin and seven other betalactam antibiotics were determined against 407 bacterial isolates. Piperacillin was found to be more active than ampicillin against susceptible gram-negative bacilli and more active than either carbenicillin or ticarcillin against Pseudomonas aeruginosa and streptococci. Although piperacillin was active against Klebsiella pneumoniae , this activity was less than that of the cephalosporins. Piperacillin was not active against penicillin-resistant Staphylococcus aureus and Enterobacteriaceae that were resistant to the other test antibiotics.

By the time-kill method, vancomycin and rifampin were antagonistic against 43 of 50 strains of Staphylococcus aureus , whether susceptible or resistant to methicillin.

Susceptibility to ampicillin and chloramphenicol in vitro has been determined for Haemophilus influenzae strains isolated from blood and/or cerebrospinal fluid cultures of patients admitted to two Atlanta hospitals from 1 January 1974 to 31 March 1975. Since the appearance of ampicillin-resistant strains of this organism in early 1974, chloramphenicol has been used in these hospitals as initial therapy for severe infection due to H. influenzae . Strains from five of 94 patients were resistant to ampicillin (minimum inhibitory concentration [MIC] ≥ 12.5 μg/ml), but all strains were susceptible to chloramphenicol (MIC < 2 μg/ml). The first 35 strains studied, including three resistant to ampicillin, were also tested for in vitro susceptibility to trimethoprim-sulfamethoxazole; all were highly susceptible (MIC ≤ 0.0312 μg of trimethoprim and 0.625 μg of sulfamethoxazole per ml).

The broth dilution method of determining the minimum inhibitory concentration (MIC) of antibiotics has been adapted to an agar shake tube technique with semisolid media. This permits the simultaneous determination of the aerobic and anaerobic MICs for facultatively anaerobic bacteria such as staphylococci.

A micromethod for performance of the serum bactericidal test is described, and the results obtained with this method are compared with those obtained with the standard tube dilution macromethod. An agreement within ± 1 dilution was achieved in 23 of 25 (92%) determinations of the serum bactericidal titer. The micromethod used approximately one-third of the amount of pooled normal human serum and of the technician's time required for performance of the macromethod. The micromethod offers an accurate and economical alternative to the macromethod for the performance of the serum bactericidal test and is particularly useful with infants and children since it minimizes blood loss.

One hundred recent clinical isolates of Campylobacter fetus subsp. jejuni were tested by an agar dilution technique for susceptibility to each of 20 antimicrobial agents. Doxycycline and gentamicin were the most active of the drugs examined, inhibiting all strains at concentrations achievable in serum. Although the median minimal inhibitory concentration of erythromycin was low, 8% of the isolates were highly resistant. All isolates of Campylobacter fetus subsp. jejuni were relatively resistant to the β-lactam antibiotics. Some strains were highly resistant to metronidazole and tinidazole.

The in vitro activity of HR 756 was compared with penicillin, cefamandole, cefoxitin, and tetracycline against Neisseria gonorrhoeae . A total of 192 randomly selected isolates (of which 23 had minimal inhibitory concentrations of ≥0.5 μg/ml for penicillin) and three β-lactamase-producing isolates were tested. HR 756 was the most active antibiotic tested, with more than 90% of the isolates inhibited by 0.008 μg/ml and all inhibited by 0.25 μg/ml.

Amphotericin B induced vacuoles in one HeLa cell line and in some unrelated cell lines. Cell growth was not affected.

Using 21 antimicrobial agents, agar dilution susceptibility tests were carried out against 190 strains of Yersinia enterocolitica . Isolates from human, environmental, and animal sources had essentially equal susceptibility patterns.

A rapid 5-h minimal inhibitory concentration procedure and a minimal bactericidal concentration procedure are described for testing Pseudomonas aeruginosa against gentamicin, tobramycin, amikacin, and carbenicillin. The rapid test results were demonstrated to correlate with the conventional tube dilution procedure.

Moxalactam was examined as a substrate for 11 β-lactamases. Hydrolysis was shown only with the β-lactamase from Bacillus cereus , a nonpathogenic bacterium. Tobramycin was assayed in tobramycin-moxalactam mixtures by using this β-lactamase.

Lack of correlation between quantitative minimal inhibitory concentration (MIC) determinations and disk diffusion susceptibility tests in our laboratory prompted a study to reevaluate the use of the disk diffusion test for sulfonamide susceptibility testing of Neisseria meningitidis . One hundred and sixty-three recent clinical isolates of N. meningitidis were examined for sulfonamide susceptibility by the agar dilution and disk diffusion methods. Optimal inocula for each of the tests were determined, and thereafter all disk diffusion tests were compared with quantitative MICs as determined by the agar dilution method using sulfadiazine and an inoculum of 10 6 colony-forming units (CFU)/ml. The clearest and most reproducible zone diameters were obtained with a 10 7 -CFU/ml inoculum in the disk diffusion test. There was complete correlation between the disk zone diameters for 300-μg disks of sulfadiazine and sulfathiazole and the agar dilution test MICs. All isolates with a zone diameter of

There has been a marked increase in the resistance of Neisseria gonorrhoeae isolated in Korea to penicillin, ampicillin, and tetracycline. In contrast, there has been no increased resistance to spectinomycin.

The release of gentamicin adenine mononucleotide transferase during single, cold, osmotic-shock treatment of Escherichia coli K-12 W677/HJR66 is not always maximal. The quantity of gentamicin adenine mononucleotide transferase in osmotic extracts could be significantly increased when a double-shock procedure was performed.

ne-3-carboxylic acid) waschosen forclinical andexpanded in vitro investigation. Cinoxacin (Lilly compound 64715) possesses manycharacteristics similar to nalidixic acid andoxolinic acid. Preliminary in vitro bacterial susceptibility studies indicate a similar gram-negative antibacterial activity to thatofnalidixic acid(2,5,7). Thisstudy presents invitro broth dilution susceptibility dataforcinoxacin against 2,968 clinical bacterial isolates plus adirect comparisonofcinoxacin andnalidixic acidminimal inhibitory concentration (MIC)andminimal bactericidal concentration (MBC)results against themostprevalent urinary tract isolates.

When mouse L929 cells are treated with amphotericin B before exposure to polyriboinosinic-polyribocytidylic acid or polyriboinosinic-polyribocytidylic acid-dextran, they make significantly more interferon than do cells not receiving amphotericin. This effect may be due to enhanced cell membrane penetration by the polynucleotide.

Thirty-two clinical isolates of Ureaplasma urealyticum were inhibited by 0.036 μg of rosaramicin per ml, whereas 25 (78%) and 13 (41%) of the strains were inhibited by this concentration of minocycline and tetracycline, respectively. These results suggest that rosaramicin may be useful for the treatment of U. urealyticum infections.

The in vitro antibacterial activity of cinoxacin was compared with that of ampicillin and chloramphenicol against 26 strains of nontyphoid Salmonella and 44 strains of Shigella . Cinoxacin was found to have a lower minimal inhibitory concentration than ampicillin and chloramphenicol against all Salmonella and Shigella sonnei strains. Cinoxacin had minimal inhibitory concentrations similar to those of chloramphenicol but lower than those of ampicillin against Shigella flexneri and S. boydii strains.

The in vitro antifungal activities of amphotericin B (AMB) and amphotericin B methyl ester (AME) were compared against 465 clinical isolates of Candida albicans . AMB and AME possessed comparable activity against half of the strains, but against the remainder of the strains the activity of AME was slightly lower than that of AMB. Rarely did AME show superior antifungal activity to AMB.

A rapid method for determining the susceptibility of yeasts to 5-fluorocytosine by using the Bactec radiometric system is described.

Cefazaflur was tested in vitro against 262 strains of bacteria. Inhibitory and bactericidal concentrations were determined with two inoculum sizes of bacterial cells in Mueller-Hinton broth and nutrient broth. Agar dilution studies also were performed. When tested in agar, 5.0 μg or less of cefazaflur per ml inhibited almost all strains of Staphylococcus aureus, Escherichia coli, Klebsiella , and Proteus mirabilis . The drug was less active against Enterobacter and indole-positive Proteus , and 7.5 μg of antibiotic per ml inhibited approximately two-thirds to one-fourth of the strains. A concentration of 50 μg of cefazaflur per ml was required for inhibition of the enterococci. There was negligible activity against Pseudomonas . The drug demonstrated less activity in broth than in agar, and a major inoculum effect was seen with some strains. For example, with a lower inoculum, 2.5 μg of cefazaflur per ml killed all strains of E. coli , whereas with the higher inoculum, 7.5 μg of cefazaflur per ml, inhibited 64% and killed only 8% of strains. The activity of the drug for some strains was greater in Mueller-Hinton broth; for others, it was greater in nutrient broth. There were considerable differences in the results of the broth and agar studies for some species when the same medium was employed. Because of differences in activity found with different media, inocula, and method of testing, an evaluation of the eventual usefulness of cefazaflur must await the results of in vivo studies.

The susceptibility of 269 isolates of Haemophilus influenzae type b to cefatrizine (BL-S640), ampicillin, and chloramphenicol was evaluated by disk diffusion susceptibility tests, using a modified Bauer-Kirby method. Broth dilution susceptibility tests were performed on 88 of these isolates, including all isolates resistant by disk to cefatrizine or ampicillin. Six of the isolates were resistant by disk to cefatrizine (zone size, H. influenzae that were resistant to cefatrizine by disk were resistant to more than 4 μg of drug per ml. The four organisms resistant to ampicillin on disk were resistant, when tested by the broth method, to >128 μg/ml. These four ampicillin-resistant H. influenzae were susceptible to 4 μg of cefatrizine per ml were susceptible to 0.5 and 2 μg of ampicillin, respectively, per ml. The activity of cefatrizine appears to be comparable in vitro to ampicillin against H. influenzae .

Productivity and property of β-lactamases of Streptomyces strains isolated from soil some 30 years ago were studied in comparison with those of the newly isolated strains. At least three-quarters of the Streptomyces strains produced β-lactamase constitutively and extracellularly, mainly as penicillinases, as in the cases of those from the newly isolated strains. Strains such as S. albus, S. diastatochromogenes, S. fradiae, and S. lavendulae were the highest producing strains, and the amounts of β-lactamase activity they produced were comparable to those produced by Bacillus cereus 569/H and B. licheniformis 749/C. In isoelectric focusing, most strains contained one main β-lactamase band with a number of satellite bands, but some strains contained one band only. Although β-lactamases from most strains showed isoelectric points of pH 5 to 6, some strains produced β-lactamases with strongly basic isoelectric points of pH 8 to 9. Molecular weights were between 20,000 and 30,000. From these results, it is suggested that the proportion of the producing strains of Streptomyces and the properties of the β-lactamases have not been affected significantly by the introduction of penicillin into the natural environment, in contrast to the cases of other microorganisms.