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PubMed1972

In vitro studies of tobramycin.

The in vitro activity of tobramycin was studied against 457 clinical isolates of gram-negative bacilli and 151 clinical isolates of gram-positive cocci. The vast majority of the gram-negative bacilli was inhibited by tobramycin at a concentration of 1.56 mug or less per ml. Only a few isolates of Staphylococcus aureus and no isolates of Streptococcus pyogenes or Diplococcus pneumoniae were susceptible to this drug. Tobramycin was generally more active than gentamicin sulfate against gram-negative bacilli, although organisms resistant to gentamicin sulfate were also resistant to tobramycin. The major difference between the two drugs was the greater activity of tobramycin against Pseudomonas aeruginosa.

Aminoglycosides↗
PubMed1973

Microbiological properties of a new cephalosporin, BL-S 339: 7-(phenylacetimidoyl-aminoacetamido)-3-(2-methyl-1,3,4-thiadiazol-5-ylthiomethyl)ceph-3-em-4-carboxylic acid.

BL-S 339 is a new broad-spectrum, parenterally effective cephalosporin whose expression of antibacterial activity in vitro is markedly affected by the nature of the assay medium. When assayed in nutrient agar, BL-S 339 was more active than cephalothin against strains of Diplococcus pneumoniae, Streptococcus pyogenes, Escherichia coli, Serratia marcescens, Klebsiella pneumoniae, Enterobacter, and indole-positive Proteus sp. However, when assayed in Mueller-Hinton medium, its activity, especially against gram-negative bacteria, was reduced substantially, whereas the activity of cephalothin was virtually unaffected by the assay medium. The in vivo activity of BL-S 339 correlated well with its activity in nutrient agar; when administered subcutaneously to mice, it was therapeutically more efficacious than cephalothin in infections caused by both gram-positive and gram-negative bacteria. When BL-S 339 was administered intramuscularly to mice, the concentrations achieved in the blood were three times those achieved with cephalothin. BL-S 339 was bound to human serum proteins to the same extent as cephalothin. Recovery of BL-S 339 in the urine within the 24-hr period after intramuscular administration to rats was three times that of cephalothin.

Animals↗
PubMed1973

Maridomycin, a new macrolide antibiotic: in vivo antibacterial activity of 9-propionylmaridomycin.

The in vivo protecting activity of 9-propionylmaridomycin, a derivative of the new macrolide antibiotic, maridomycin, was compared with that of other macrolide antibiotics in mice infected with Staphylococcus aureus, Streptococcus pyogenes, and Diplococcus pneumoniae. The protective effect was almost similar to that afforded by several known macrolide antibiotics in mice infected intraperitoneally with certain strains of the gram-positive species described above. The skin lesion caused by intradermal challenge of S. aureus in mice also responded very effectively to treatment with 9-propionylmaridomycin.

Aminoglycosides↗
PubMed1974

Interaction of clindamycin and gentamicin in vitro.

The minimal inhibitory concentrations of clindamycin and gentamicin alone and in combinations were determined by a microdilution method for 163 aerobic, facultative, and anaerobic clinical isolates. All 77 strains of Staphylococcus aureus, Diplococcus pneumoniae, Streptococcus pyogenes, and anaerobic bacteria (except for three strains of Clostridium) were inhibited by 1.6 mug or less of clindamycin per ml. Gentamicin did not interfere with the activity of clindamycin within the range of concentrations tested (0.1 to 100 mug/ml); for some strains combinations were synergistic. Sixty-two (94%) of 66 strains of Enterobacteriaceae and Pseudomonas aeruginosa were inhibited by 6.2 mug or less of gentamicin per ml. Combinations of clindamycin and gentamicin were indifferent for 29 strains and synergistic for 33 strains. All 20 strains of enterococcus, three strains of Clostridium, three strains of Escherichia coli, and one strain of Proteus rettgeri were resistant to both clindamycin (minimal inhibitory concentration greater than 3.1 mug/ml) and gentamicin (minimal inhibitory concentration greater than 6.2 mug/ml). Combinations of clindamycin and gentamicin were indifferent for 16 and synergistic for 11 of the resistant strains. Except for clindamycin-sensitive isolates, synergy was usually observed only at concentrations of one or both drugs which are not readily obtainable in vivo. Antagonism was never observed.

Anti-Bacterial Agents↗
PubMed1976

Susceptibility of pneumococci and Haemophilus influenzae to antibacterial agents.

Strains of Diplococcus pneumoniae and Haemophilus influenzae were tested for susceptibility to numerous antibiotics by a twofold agar dilution method using an inocula replicator. Undiluted, fully grown broth cultures were used as inocula for both species, and cultures of pneumococci diluted 1:1,000 were also tested. The antibiotics included most of those in common use in the United States as well as some chemical modifications recently approved and others that are under investigation. The most striking aspect of the results was the marked susceptibility of the pneumococci to all the antibiotics tested except the polymyxins and most of the aminoglycoside antibiotics, although some new aminoglycosides were active in quite low concentrations. Some of the strains of pneumococci were of decreased susceptibility to penicillin G (minimal inhibitory concentrations, 0.2 to 0.4 mug/ml), but none were tetracycline resistant, although such strains had been reported previously from this laboratory. The strains of H. influenzae, which were all serologically nontypable, exhibited different patterns of susceptibility to the groups of antibiotics and to the individual chemically related ones. None of these strains (isolated early in 1972) were ampicillin resistant. The most active agents against H. influenzae were: carbenicillin and ampicillin, analogues related to each of them, rifampin, chloramphenicol, and the polymyxins. However, the tetracycline analogues other than tetracycline, some aminoglycosides, notably tobramycin, kanamycin, gentamicin, and verdamicin, erythromycin, and some new lincomycin analogues were also active in low concentrations. Trimethoprim alone was highly active, and in combination with sulfamethoxazole it was even more active and synergistic against strains of both D. pneumoniae and H. influenzae.

Aminoglycosides↗
PubMed1976

Activity of cefamandole and other cephalosporins against aerobic and anaerobic bacteria.

The activity of cefamandole was comparable to that of cephalothin, cefazolin, and cephaloridine against Staphylococcus aureus, Streptococcus pyogenes, and Diplococcus pneumoniae. In contrast, cefamandole was considerably more active than cephalothin, cefazolin, or cephaloridine against gram-negative facultative bacilli, including Haemophilus influenzae, the most striking disparities being noted with indole-positive Proteus and Enterobacter. Bacteroides fragilis was more susceptible to cefoxitin than to cefamandole or cefazolin (median minimal inhibitory concentration, approximately 8, 32, and 32 mug/ml, respectively); cephalothin exhibited still less activity against this species. The majority of other anaerobes were inhibited by relatively low concentrations of all four cephalosporins. The results indicate a potentially valuable role for cefamandole against facultative gram-negative bacilli, including H. influenzae, but no exceptional activity against anaerobes.

Aerobiosis↗
PubMed1968

Biological characterization of prasinomycin, a phosphorus-containing antibiotic.

Prasinomycin, a new antibiotic from the green spore streptomycete, Streptomyces prasinus, primarily inhibits the growth of gram-positive microorganisms. Like penicillin, it is effective only against growing cells. Though primarily bacteriostatic at levels about the minimal inhibitory concentration, it is bactericidal at higher levels. Neither synergism nor antagonism could be demonstrated for prasinomycin with a variety of other antibiotics. It is highly active upon subcutaneous administration to mice infected with Staphylococcus aureus, Streptococcus pyogenes C203, or Diplococcus pneumoniae. Prasinomycin has a unique prophylactic action whereby one dose protects mice against experimental infections for as long as 2 months. It is more effective against S. aureus infections in mice when administered subcutaneously 20 hr prior to infection than when given in divided doses 1 hr before and 4 hr after infection.

Anti-Bacterial Agents↗
PubMed1968

In vitro antimicrobial activity and human pharmacology of cephaloglycin.

Serum and urine concentrations of cephaloglycin (an orally absorbed derivative of cephalosporin C) were determined in normal volunteers and in patients. The in vitro activity of cephaloglycin was also studied. All strains of group A streptococci (Streptococcus pyogenes) and Diplococcus pneumoniae were inhibited by 0.4 mug of cephaloglycin per ml. Eighty per cent of the Staphylococcus aureus strains and about 50% of the Escherichia coli and Proteus mirabilis strains were inhibited by 1.6 mug of cephaloglycin per ml. Klebsiella-Aerobacter species were more resistant to cephaloglycin and 12.5 mug per ml was required to inhibit 70% of these strains. When single doses of 250, 500, or 1,000 mg of cephaloglycin were administered to fasting volunteers, a peak serum concentration of at least 0.5 mug per ml was achieved. A full breakfast did not interfere with absorption of cephaloglycin. Probenecid enhanced both the peak serum concentration and the duration of antibiotic activity in the serum. Serum concentrations of cephaloglycin were even higher in patients who were receiving repeated doses. The peak serum concentrations of cephaloglycin in all volunteers and patients were adequate to inhibit all strains of group A streptococci and D. pneumoniae. Many of the peak serum concentrations were adequate to inhibit some strains of S. aureus, E. coli, and P. mirabilis. Urine levels of cephaloglycin were high enough in all volunteers and patients to inhibit more than 90% of the E. coli and P. mirabilis strains and over 70% of the strains of Klebsiella-Aerobacter.

Bacteria↗
PubMed1969

In vitro antimicrobial activity and human pharmacology of cephalexin, a new orally absorbed cephalosporin C antibiotic.

Concentrations of cephalexin (an orally absorbed derivative of cephalosporin C) in serum and urine were determined in normal volunteers and patients. The in vitro antibacterial activity was also studied. All strains of group A beta-hemolytic streptococci and Diplococcus pneumoniae were inhibited by 3.1 mug/ml. Of the Staphylococcus aureus strains, 88% were inhibited by 6.3 mug/ml, and 12.5 mug/ml was inhibitory for all S. aureus, 80% of Escherichia coli, 72% of Klebsiella-Aerobacter, and 56% of Proteus mirabilis strains. About 90 to 96% of E. coli, Klebsiella Aerobacter, and P. mirabilis strains were inhibited by 25 mug of cephalexin per ml. Pseudomonas and indole-positive Proteus strains proved to be quite resistant to cephalexin. Cephalexin was well absorbed after oral administration. A peak serum concentration of cephalexin of at least 5 mug/ml was achieved in each volunteer with 250 and 500-mg doses. A mean peak serum concentration of 7.7 mug/ml was achieved with 250-mg doses; 12.3mug/ml was achieved with 500-mg doses of antibiotic. Food did not interfere with absorption. Probenecid enhanced both the peak serum concentration and the duration of antibiotic activity in the serum. Over 90% of the administered dose was excreted in the urine within 6 hr. The mean peak serum concentration of cephalexin after an oral dose of 500 mg was adequate to inhibit all group A streptococci, D. pneumoniae, and S. aureus, 85% of E. coli, and about 40 to 75% of Klebsiella-Aerobacter and P. mirabilis strains. Levels of cephalexin in urine were adequate to inhibit over 90% of E. coli, and P. mirabilis and 80 to 96% of Klebsiella-Aerobacter strains.

Cephalosporins↗
PubMed1969

Microbiological and pharmacological behavior of 7-chlorolincomycin.

Replacement of the 7-(R) hydroxyl group of lincomycin by a 7-chloro-substituent produced a compound with greater in vitro activity than the parent. Laboratory studies of this compound showed it to be highly active against all of the following strains of gram-positive organisms examined, including penicillinase- and nonpenicillinase-producing staphylococci, Diplococcus pneumoniae, Streptococcus viridans and Streptococcus pyogenes. The enterococci, as well as all the gram-negative organisms tested, with the exception of some strains of Haemophilus, were uniformly insensitive to this agent. The activity of 7-chlorolincomycin was not affected by serum or inoculum size. Resistance developed in a slow stepwise pattern. Peak levels of approximately 2 mug/ml were achieved in the serum of volunteers after ingestion of 150 mg either in the fasting state or after a meal. No untoward effects were noted. The antibiotic appears to be of potential value in the treatment of infections due to gram-positive organisms, with the exception of enterococcus.

Adult↗
PubMed1971

Detection of bacteremia in children with sodium polyanethol sulfonate: a prospective clinical study.

A prospective study was made of 1,000 consecutive duplicate blood cultures obtained from sick children to evaluate the usefulness of sodium polyanethol sulfonate (SPS). With the small volumes of blood (1 to 5 ml) usually obtained for blood cultures in children, SPS did not increase the frequency of recovery of organisms judged to be associated with clinical infections, with the possible exception of Diplococcus pneumoniae. However, the use of SPS was associated with an increased frequency of recovery of organisms judged to be contaminants, such as Staphylococcus epidermidis and propionibacteria, possibly because SPS enhanced the recovery of a very small inoculum of skin bacteria.

Anticoagulants↗
PubMed1971

Cephapirin: in vitro antibacterial spectrum.

Cephapirin, a new semisynthetic cephalosporin derivative, was found to have an antibacterial spectrum similar to that of cephalothin. Staphylococcus aureus was inhibited by cephapirin concentrations of 0.09 to 12.5 mug/ml. S. epidermidis, S. viridans, S. pyogenes, and Diplococcus pneumonia isolates were inhibited by less than 1 mug/ml. The Enterococcus required a concentration of 25 mug of antibiotic per ml for inhibition. Approximately 65% of Escherichia coli, and all Klebsiella, indole-negative Proteus, and Salmonella strains tested were inhibited by the drug. Serratia, Pseudomonas, indole-positive Proteus, and Erwinia strains were highly resistant. Inoculum size was not an important factor in determining the level of sensitivity of S. aureus to cephapirin. The antibiotic does not appear to be significantly bound to serum protein. In vitro development of resistance to the drug was demonstrated with two isolates of S. aureus.

Bacteria↗
PubMed1973

Effect of osmotic stabilizers on 14 CO 2 production by bacteria and blood.

Evolution of (14)CO(2) by whole blood as well as by Diplococcus pneumoniae, Haemophilus sp., Pseudomonas aeruginosa, Pseudomonas diminuta, and Streptococcus pyogenes was examined by using the BACTEC system. The control medium was JLI no. 6A culture vial containing 30 ml of enriched tryptic soy broth and 1.5 muCi of (14)C-substrate. Hypertonic media consisted of control medium with either 1 or 3% NaCl, 10% sucrose, and 5%, 10%, or 15% dextran. The most deleterious treatment to bacteria was 3% NaCl since it not only retarded (14)CO(2) production, but also prevented growth of D. pneumoniae, Haemophilus, and P. diminuta. The 10% sucrose treatment diminished (14)CO(2) output, although it did not retard growth of test organisms. This effect was probably due to (14)C-substrate dilution rather than to osmotic effects. Dextran had slight effect on (14)CO(2) production and slightly acidified the medium. Of the treatments tested, only 10% sucrose reduced normal output of (14)CO(2) by whole blood. This also is probably due to (14)C-substrate dilution. It appears that 10% sucrose is potentially the most useful osmotic agent for radiometric techniques since, although bacterial (14)CO(2) production is lowered, blood (14)CO(2) is lowered also.

Bacteria↗
PubMed1973

Use of technetium ( 99m Tc) as a bacterial label in lung clearance studies.

The suitability of technetium ((99m)Tc), a gamma emitter, for labeling of Diplococcus pneumoniae in studies of lung bacterial clearance was examined. A killed bacterial slurry with high specific activity was obtained with a ferric ascorbate reducing system. Approximately 5.5% of radioactive counts dissociated from labeled bacteria in 6 h. Rats were exposed to a uniformly mixed aerosol of untagged, viable pneumococci and killed, (99m)Tc-tagged pneumococci. The aerodynamic behavior of labeled and unlabeled pneumococci was similar. Viable bacterial counts and radioactive counts were determined in lung homogenates at intervals following exposure, and rates of bacterial killing and disappearance of radioactive counts were plotted. Radioactive counts did not increase in the liver during the period of observation, suggesting that the decrease in lung radioactivity represents mucociliary clearance and not release of isotope to the systemic circulation. The use of (99m)Tc for bacterial labeling provides advantages of technical simplicity and personnel safety compared to the use of beta-emitting isotopes.

Aerosols↗
PubMed1973

Disk test for the differentiation of pneumococci from other alpha-hemolytic streptococci.

One hundred twenty-five strains of Diplococcus pneumoniae and one hundred twenty-five strains of other alpha-hemolytic streptococci were planted on horse red cell-Brucella agar, and a disk of methicillin was placed on each inoculated plate. All strains were incubated anaerobically at 37 C for 24 h and then exposed to air at 6 C for 48 h. All strains of pneumococci produced a ring of beta-hemolysis surrounding the zone of inhibition produced with the methicillin disk, whereas no strain of alpha-hemolytic streptococci produced beta-hemolysis. It is suggested that this new criterion is useful for the differentiation of pneumococci from other alpha-hemolytic streptococci in those cases where other characteristics were insufficient for an unequivocal identification.

Aerobiosis↗
PubMed1974

Critical-point drying: rapid method for the determination of bacterial extracellular polymer and surface structures.

The relative amount of extracellular polymer which remains about Azotobacter vinelandii, Zoogloea ramigera, Klebsiella pneumoniae, and Diplococcus pneumoniae after critical-point drying was studied by electron microscopy. The results obtained with this technique are compared to those obtained with methods that illustrate extracellular polymer, such as freeze-etching and ruthenium red staining. Comparative results indicate critical-point drying to be a rapid, reliable method for the determination of capsule-like polymer surrounding bacterial cells. In addition, critical-point drying can be used to observe morphogenetic changes, such as vesicle production.

Azotobacter↗
PubMed1974

Influence of the alternate complement pathway in opsonization of several bacterial species.

In normal human serum chelated with magnesium (10 mM) and ethylene glycotetraacetic acid (10 mM) (MgEGTA), the classical pathway of complement activation is blocked; however, the alternate pathway of complement activation is intact. Diplococcus pneumoniae, Staphylococcus albus, Streptococcus viridans, Streptococcus faecalis, and Serratia marcescens were opsonized in normal human serum containing 10 mM MgEGTA. In contrast, Staphylococcus aureus and Pseudomonas aeruginosa were poorly opsonized in human serum chelated with 10 mM MgEDTA. Therefore certain bacterial species appear to require the classical pathway of complement activation to be opsonized and other bacterial species utilize the alternate pathway of complement activation.

Acetates↗
PubMed1975

Reactivation of latent Herpes simplex virus after pneumococcal pneumonia in mice.

In attempts to reactivate latent herpes simplex virus, we instilled Diplococcus pneumoniae intratracheally into mice harboring latent infections in sacrosciatic spinal ganglia. All mice developed a severe pneumonia within 24 h and were given penicillin therapy. Representative mice that survived the penumonia were sacrificed at daily intervals, and appropriate tissues were examined for evidence of viral reactivation. Herpes simplex virus was reactivated in the ganglia and appeared to travel both proximally and distally in associated nerve trunks. Clinically apparent disease due to the virus was not detected in any mice.

Animals↗