bluuebunny/crossref_metadata_2025 huggingface dataset:
New Plasmid-Mediated Nucleotidylation of Aminoglycoside Antibiotics in
Staphylococcus aureus
Authors: Goffic F. Le , Martel A. , Capmau M. L. , Baca B. , Goebel P. , Chardon H. , Soussy C. J. , Duval J. , Bouanchaud D. H.
Published: June 2012

A wild-type strain of
Staphylococcus aureus
, which inactivates a wide variety of aminoglycosides (except the gentamicin components), has been found to harbor a plasmid (RAp01) that mediates the biosynthesis of a nucleotidyltransferase. This enzyme modifies the 4′-hydroxy function of these antibiotics. The plasmid has been studied, the enzyme responsible for this resistance pattern has been isolated by affinity chromatography, and its kinetics and physicochemistry have been characterized. The target of this enzyme has also been located by demonstrating the structure of one inactivated compound, 4′-(
O
)-adenylyltobramycin.
In Vitro Evaluation of the New Oral Cephalosporin Cefatrizine: Comparison with Other Cephalosporins
Authors: Blackwell C. Caroline , Freimer Earl H. , Tuke Gregory C.
Published: June 2012

Cefatrizine (BL-S640), a semisynthetic, orally administered cephalosporin, was found to have an in vitro spectrum of activity comparable to those of four other cephalosporins tested. It is as effective as cephalexin, the other orally administered cephalosporin evaluated, against most species, and it appears to be more effective than cephalexin against many
Enterobacter, Haemophilus
, and
Proteus
strains isolated in our hospital. It is not inactivated by the plasmid-determined β-lactamases of 14 strains of ampicillin-resistant
Salmonella typhimurium
or the ampicillin resistance determinant of an
H. influenza
strain from the Center for Disease Control. No synergy was observed between cefatrizine and gentamicin, kanamycin, carbenicillin, or polymyxin when tested against selected strains.
Genetic Basis of Streptococcin A-FF22 Production
Authors: Tagg J. R. , Wannamaker L. W.
Published: June 2012

Spontaneous, low-frequency loss of ability to produce streptococcin A-FF22 (SA) by group A streptococcus strain FF22 was observed. The proportion of non-SA-producing (SA
−
) derivatives occurring in strain FF22 cultures grown in Todd Hewitt broth supplemented with 1% of yeast extract (THBY) was increased on treatment with ethidium bromide, acriflavin, or rifampin. The highest incidence of SA
−
organisms, however, was found in untreated THBY cultures that had been aging by incubation at 37°C for several months. The possibility of selective effects in these experiments, operating to enhance the apparent frequency of SA
−
bacteria, was discounted. The survival of SA
−
derivatives in association with populations of SA
+
bacteria was dependent upon the use of culture conditions inimical to SA activity, since a consistent finding was that the loss of ability to produce SA was associated with loss of immunity to the killing action of this bacteriocin. Whereas selective killing of SA
−
derivatives was evident in mixed cultures of SA
+
and SA
−
strains in tryptic soy broth, no such effect was demonstrable in THBY. In these experiments, elimination of SA
−
cells seemed directly related to the presence of active SA. Purified clones of SA
−
substrains did not seem revertible to SA production, either spontaneously or on treatment with nitrosoguanidine. It is suggested that the property of production of SA by group A streptococcus strain FF22, together with that of host cell immunity to the homologous bacteriocin, may be mediated by plasmid-borne genetic determinants.
Susceptibility of
Haemophilus influenzae
Type b to Cefatrizine, Ampicillin, and Chloramphenicol
Authors: Brotherton Thomas , Lees Tracy , Feigin Ralph D.
Published: June 2012

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, <16 mm), four were resistant to ampicillin (zone size, <19 mm), and none were resistant to chloramphenicol (zone size, <17 mm). Only two of the six isolates of
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. The two isolates resistant 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
.
Pharmacological Study of Cefazolin During Intermittent and Continuous Infusion: a Crossover Investigation in Humans
Authors: Thys J. P. , Vanderkelen B. , Klastersky J.
Published: June 2012

Levels of cefazolin were determined in plasma, urine, bile, and cerebrospinal fluid in humans after a bolus intravenous injection and during a controlled, continuous intravenous infusion. All the patients were studied in a steady-state and crossover fashion. In plasma, the mean peak level after bolus injection (1.5 g) studied in 12 patients was 206.5 μg/ml; during continuous infusion (6 g daily), the mean level remained stable at 52.6 μg/ml. With bolus injection and continuous infusion, respectively, 89.7 and 86.3% of the administered dose of cefazolin were excreted in the urine of nine patients over the 6-h period considered. The levels of cefazolin in common bile duct bile were studied in six cholecystectomized patients. In bile collected during the two 3-h periods of the experiment, the mean concentration of the drug in the bile after bolus injection was 66.9 and 22.0 μg/ml, respectively; during continuous infusion, the corresponding biliary levels were 50.7 and 51.3 μg/ml, respectively. In four neurosurgical patients with an intraventricular catheter, neither bolus injection nor continuous infusion resulted in a demonstrable concentration of cefazolin in the cerebrospinal fluid. The continuous intravenous administration of cefazolin might have some advantage over the intravenous bolus intermittent injections. In plasma, the area under the curve is greater with continuous infusion than with bolus injection. In bile, the levels of cefazolin are more sustained with continuous infusion than with bolus injection. This approach to intravenous administration of cefazolin deserves more pharmacological and clinical trials.
Mutants of
Pseudomonas aeruginosa
That Show Specific Hypersensitivity to Aminoglycosides
Authors: Mills B. J. , Holloway B. W.
Published: June 2012

A class of mutants in
Pseudomonas aeruginosa
have been found that are tolerant to aeruginocin 41 and also hypersensitive to aminoglycosides. They do not show any changes in susceptibility to a wide range of other toxic agents, including antibiotics and surfactants. This
tol
locus,
tolA
, has been mapped at 10 min from the FP2 origin and linked to
carA
(carbamyl phosphate synthetase) by transduction and conjugation. By selecting for revertants of the hypersensitivity phenotype, revertants to
tol
+
were found, indicating that it is the
tolA
locus that is responsible for this specific hypersensitivity. The results indicate that a specific mechanism exists for the intrinsic resistance of
P. aeruginosa
to aminoglycosides.
Comparative Pharmacokinetics of Cefamandole, Cephapirin, and Cephalothin in Healthy Subjects and Effect of Repeated Dosing
Authors: Barza Michael , Melethil Srikumaran , Berger Stephen , Ernst E. Chaim
Published: June 2012

Cefamandole nafate, cephapirin, and cephalothin were administered intravenously in crossover fashion to 12 volunteers, in dosages of 2 g every 6 h for 16 doses. Mean peak levels of cefamandole were approximately 50% higher than those of the other agents. The serum concentration curves appeared to decline bi-exponentially, suggesting that a two-compartment model was most applicable for pharmacokinetic analysis; accordingly, the
t
½
of cefamandole was significantly longer when the serum peak was omitted from the analysis (0.86 versus 0.73 h,
P
< 0.05). The half-lives of cephalothin and cephapirin, 0.34 and 0.36 h, respectively, were probably underestimates reflecting the inclusion of distribution-phase values in the calculation. Repeated dosing had no effect on the peak serum levels, half-life, serum clearance, or apparent volume of distribution with one exception: peak serum levels of cephapirin were significantly lower after the sixteenth than after the first dose. Marked variations within a given subject were noted in the half-life and apparent volume of distribution of cefamandole in several instances. Renal clearances of cefamandole exhibited saturation kinetics similar to those of penicillin G.
Reversible Thrombocytosis and Anemia Due to Miconazole Therapy
Authors: Marmion LeRoy C. , Desser Kenneth B. , Lilly Ralph B. , Stevens David A.
Published: June 2012

Miconazole was administered intravenously in six consecutive patients with, active coccidioidal infection. Such treatment was associated with progressive anemia and thrombocytosis. The hematological abnormalities appeared to be dose related and potentially reversible. Bone marrow studies demonstrated erythroid hypoplasia and increased or active platelet production in three subjects. No hemorrhagic or thrombotic episodes were identified. It is suggested that careful hematological monitoring be performed in subjects undergoing systemic miconazole therapy.
In Vitro Synergistic Effect of Netilmicin, a New Aminoglycoside Antibiotic
Authors: Fu Kwung P. , Neu Harold C.
Published: June 2012

The combination of netilmicin (Sch 20569) with carbenicillin, cefazolin, chloramphenicol, and clindamycin was evaluated by in vitro tests against 91 clinical isolates of
Pseudomonas, Klebsiella
, and
Escherichia coli
. Combinations were considered to show synergy if there was a fourfold or greater reduction in minimal inhibitory concentration values of both antibiotics when combined. Synergy of netilmicin with carbenicillin could be demonstrated against 21 of 46
Pseudomonas
isolates. Comparison of the synergy of carbenicillin with netilmicin or gentamicin showed that netilmicin was less active than gentamicin against
Pseudomonas aeruginosa
. However, at therapeutic concentrations of the antibiotics, significant differences were not observed. Synergy of netilmicin and cefazolin was demonstrated against only 1 of 21
Klebsiella
strains tested, but partial synergy was found for 12 of 20 isolates. Synergy and antagonism were uncommon with the netilmicin-chloramphenicol and netilmicin-clindamycin combinations against
E. coli
and
Pseudomonas
.
Growth of
Physarum gyrosum
on Agar Plates and in Liquid Culture
Authors: Taylor Richard L. , Mallette M. F.
Published: June 2012

The physical and nutritional requirements of the antibiotic-producing slime mold
Physarum gyrosum
were examined to develop a liquid medium for this myxomycete. Liquid culture is desired to expedite a useful scale of production of antibiotic materials for ease of isolation and structure study. Culture conditions were selected to favor antibiotic production rather than maximum growth. The medium devised consisted of 0.010 M potassium phosphate buffer (pH 6.0), 2% bakers' yeast, and 0.2% glucose and was supplemented with either 10
−7
M hemoglobin (preferred) or 2.0 ml of live
Escherichia coli
per 100 ml of culture medium grown to a steady-state population in nutrient broth. The slime mold, which contained some
E. coli
carried along with the inoculum, was allowed to grow as a surface plasmodium at 20°C in the dark with weekly subculturing for stocks or for 10 days for antibiotic production.
P. gyrosum
produced the same antibiotic materials when grown in liquid medium as it did when grown on agar plates. A seeded plate disk assay against
Bacillus cereus
was employed to follow antibiotic activity.
Tirandamycin, an Inhibitor of Bacterial Ribonucleic Acid Polymerase
Authors: Reusser Fritz
Published: June 2012

The antibiotic tirandamycin (a 3-acyltetramic acid structurally related to streptolydigin) specifically inhibits transcription by interfering with the function of bacterial ribonucleic acid polymerase. Ribonucleic acid polymerases from rat liver nuclei are not subject to tirandamycin inhibition. Qualitatively, the mode of action of the antibiotic is identical to that of streptolydigin in inhibiting chain initiation as well as chain elongation during the transcriptional process. However, tirandamycin is approximately 40 times less potent than streptolydigin. The structures of the 3-acyl groups of the two acyltetramic acid antibiotics tirandamycin and streptolydigin differ only slightly in the degree of oxidation of the terminal dioxabicyclo (3.1)nonane system and possess the same stereochemistry (D. J. Duchamp, A. R. Branfman, A. C. Button, and K. L. Rinehart, 1973). More significantly, major differences occur at the 1 and 5 positions of the tetramic acids. Tirandamycin contains no substituents; streptolydigin contains a substituted acetamide function at position 5 and a sugar moiety at position 1. The lack of substituents at the 1 and 5 positions of the tetramic acid portion in tirandamycin is probably responsible for the reduced biopotency of tirandamycin as compared with streptolydigin.
Metabolism of [
14
C]Cefaclor, a Cephalosporin Antibiotic, in Three Species of Laboratory Animals
Authors: Sullivan Hugh R. , Due Susan L. , Kau Donald L. K. , Quay John F. , Miller Warren M.
Published: June 2012

The metabolic fate of the orally effective cephalosporin antibiotic cefaclor (Lilly 99638) has been studied in rats, mice, and dogs. Cefaclor is efficiently absorbed from the gastrointestinal tract as the intact antibiotic. In rats and mice, cefaclor, for the most part, escapes metabolism in the body and is eliminated unchanged as unaltered antibiotic, primarily by renal excretion. In dogs, however, cefaclor is more labile to metabolism and only a portion of the administered antibiotic is eliminated unchanged via the kidney.
Antimicrobial Susceptibility Testing of Yeasts: a Turbidimetric Technique Independent of Inoculum Size
Authors: Galgiani John N. , Stevens David A.
Published: June 2012

The current development of potent antifungal drugs necessitates reliable methods of in vitro susceptibility testing of clinical isolates. Other laboratories have noted with some antimicrobials that conventional tube dilution visual end points for determining minimal inhibitory concentrations (MIC) vary markedly with the inoculum. With seven isolates (four species) we compared the conventional method with one developed with a spectrophotometer. Yeasts were diluted to inocula of 10
2
to 10
5
cells/ml and incubated at 37°C with 5-fluorocytosine or miconazole or without drug in a synthetic defined medium. At frequent intervals MICs were determined by the lowest drug concentration without visible turbidity. Concurrently, the percent transmission of each tube was measured and an inhibitory concentration (IC
½
) was calculated from the turbidimetric measurements. MICs of both drugs for all strains varied with the inoculum. Intrastrain differences averaged 128-fold for miconazole and greater than 8-fold with 5-fluorocytosine. This variability in MIC occurred when readings were made after 12 to 48 h of incubation. In contrast, IC
½
values of all isolates varied less than two-fold with the same range of inocula. Most isolates showed this independence when measured at 48 h. Fast-growing yeasts showed greater IC
½
variability unless the turbidimetric measurements were taken earlier while the drug-free growth was still in a rapid growth phase. This method is reproducible, inoculum independent, rapid, free from subjectivity and observer variability, and suitable for adaptation to a clinical setting.
R-Plasmid Transfer In Vivo in the Absence of Antibiotic Selection Pressure
Authors: Petrocheilou V. , Grinsted J. , Richmond M. H.
Published: June 2012

The persistence of an O18
Escherichia coli
strain resistant to tetracycline, streptomycin, and sulfonamide has been followed in the fecal flora of a single individual over a period of 9 months. The strain in question carrying an R plasmid was detectable from the beginning of the survey, but it was only after a 10-day period of tetracycline therapy that it reached an all but permanent dominance in the fecal flora. No transfer of the R plasmid carried by the strain to any other coliform could be detected for 202 days after the end of tetracycline treatment. At this point, however, an O88
E. coli
carrying the same plasmid as the O18 strain appeared briefly as a predominant component of the flora. The two plasmids isolated from the O18 and the O88
E. coli
strains have been characterized in molecular terms and found to be similar. This suggests that R-plasmid transfer between two
E. coli
strains occurred in an individual who was living a normal daily life and who was not receiving antibiotics.
R Plasmids in
Streptococcus agalactiae
(Group B)
Authors: Horodniceanu Thea , Bouanchaud D. H. , Bieth G. , Chabbert Y. A.
Published: June 2012

Two plasmids determining resistance to tetracycline (RIP500) and to chloramphenicol, erythromycin, lincomycin, and pristinamycin I (RIP501) were isolated from a strain of
Streptococcus agalactiae
. The frequency-of-resistance loss is very low for RIP500 (<3 × 10
4
) but higher for RIP501 (the efficiency was dependent upon the curing agents and incubation temperature and varied between 0.5 and 96%). Derivatives susceptible to all drugs were also obtained. RIP500 and RIP501 have similar molecular weights (17.9 × 10
6
and 20 × 10
6
, respectively) and represent different percentages of total deoxyribonucleic acid (0.4 and 4%, respectively). The number of copies of RIP500 and RIP501 per cell is different, and these plasmids are likely replicated under different kinds of control (stringent and/or relaxed). No plasmid deoxyribonucleic acid was found in a derivative of strain B96 susceptible to all drugs.
Effect of Osmolality on the Response of
Escherichia coli
to Mecillinam
Authors: Greenwood David
Published: June 2012

The influence of osmolality on the effect of the novel β-lactam antibiotic, mecillinam, on
Escherichia coli
was examined in a turbidimetric system. Both sucrose and sodium chloride were able to protect
E. coli
from the effects of mecillinam during the stage of conversion to morphologically abnormal forms, and the additional presence of small amounts of magnesium sulfate protected the spherical forms from subsequent lysis. More phenotypically “resistant” survivors were recovered in osmotically protective media than in broth of low osmolality. Sucrose appeared a better protective agent than sodium chloride, but growth of the phenotypically resistant population was much slower in the sucrose-containing than in sodium chloride-containing medium.
Ticarcillin in Combination with Cephalothin or Gentamicin as Empiric Antibiotic Therapy in Granulocytopenic Cancer Patients
Authors: Schimpff Stephen C. , Landesman Sheldon , Hahn Davis M. , Standiford Harold C. , Fortner Clarence L. , Young Viola Mae , Wiernik Peter H.
Published: June 2012

Ticarcillin was used in combination with either cephalothin or gentamicin as initial empiric antibiotic therapy for 127 patient trials of suspected infection in granulocytopenic cancer patients. Bacteremia was present in 20%, nonbacteremic microbiologically documented infections in 21%, clinically documented infections in 23%, and possible infections in 5%; infection was doubtful in 31%. Although
Staphylococcus aureus
was the most common single organism isolated (23%), gram-negative bacilli accounted for 54% of all pathogens. Both antibiotic regimens were highly efficacious, with complete resolution in 46% of bacteremias, 88% of nonbacteremic microbiologically documented infections, and 95% of clinically documented infections. Among bacteremias, 8 of 9 caused by
S. aureus
but only 4 of 15 (27%) caused by gram-negative bacilli were completely resolved with these antibiotic combinations. Reasons for nonresponse in bacteremias were persistent granulocytopenia, mixed infection and, in two patients, antibiotic-resistant organisms. Toxicities other than hypokalemia were minimal. Although the rate of further infections was high overall (18/127), only one occurred among the 39 patients with <4 days of antibiotic therapy. Ticarcillin in combination with either cephalothin or gentamicin was effective as initial empiric therapy of suspected infection in granulocytopenic cancer patients.
Effect of 9-β-
d
-Arabinofuranosyladenine 5′-Monophosphate and 9-β-
d
-Arabinofuranosylhypoxanthine 5′-Monophosphate on Experimental Herpes Simplex Keratitis
Authors: Kaufman Herbert E. , Varnell Emily D.
Published: June 2012

Treatment of established experimental keratitis caused by herpes simplex virus with 9-β-
d
-arabinofuranosyladenine 5′-monophosphate (Ara-AMP) or 9-β-
d
-arabinofuranosylhypoxanthine 5′-monophosphate (Ara-HxMP) showed that the Ara-AMP, in a concentration of 2 or 20%, had a significant effect on the keratitis but that 0.4% Ara-HxMP showed only minimal activity. Ara-AMP was also effective in the treatment of idoxuridine-resistant keratitis. No local toxicity with a high concentration (20%) of Ara-AMP was seen, but the duration of therapy was brief.
Antibiotic Synergy and Antagonism Against Clinical Isolates of
Klebsiella
Species
Authors: D'Alessandri Robert M. , McNeely David J. , Kluge Ronica M.
Published: June 2012

Minimal inhibitory concentrations of kanamycin, gentamicin, amikacin, cephalothin, and chloramphenicol were determined in Trypticase soy broth for 70 clinical isolates of
Klebsiella
species. Gentamicin and amikacin were the most active on a weight basis. Chloramphenicol was more active than kanamycin, and cephalothin was the least active of all. Studies using a microtiter modification of the checkerboard technique were performed to evaluate the comparative activity of the three aminoglycosides in combination with either chloramphenicol or cephalothin. The cephalothin-aminoglycoside combinations demonstrated synergy in >80% of the isolates tested. No antagonism was noted. The chloramphenicol-aminoglycoside combinations showed antagonism in 35 to 45% of the isolates tested. The data suggest that the chloramphenicol-aminoglycoside combinations be used with caution when treating serious infections where
Klebsiella
is a potential pathogen.
Comparison of Josamycin and Erythromycin in the Therapy of
Mycoplasma pneumoniae
Pneumonia
Authors: Wenzel Richard P. , Hendley J. Owen , Dodd Wendell K. , Gwaltney Jack M.
Published: June 2012

A controlled, double-blind study was performed to compare the efficacy of two macrolide antibiotics, erythromycin and josamycin, in the therapy of
Mycoplasma pneumoniae
pneumonia. Marine Corps recruit volunteers received one of the two antibiotics in a dosage of 2 g daily for 7 days. Twelve of 21 men treated with josamycin and 9 of 25 men treated with erythromycin had confirmed
M. pneumoniae
pneumonia. The josamycin-treated group remained hospitalized for 5.4 ± 1.2 days compared to 5.1 ± 2.0 days for the erythromycin-treated group (0.60 >
P
> 0.50). Fever days were similar for the josamycin-treated (1.4 ± 0.4) and erythromycin-treated (1.2 ± 0.3) groups (
P
= 0.95). There was no difference in resolution of signs and symptoms of illness in the two study populations. Thus, josamycin is as efficacious as erythromycin in the therapy of
M. pneumoniae
pneumonia.
Cultivation of
Staphylococcus aureus
in a Synthetic Medium of Low Ultraviolet Absorptivity
Authors: Charles B. G. , Rawal B. D.
Published: June 2012

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.
Rapid Analysis of Cefazolin in Serum by High-Pressure Liquid Chromatography
Authors: Wold John S.
Published: June 2012

A high-pressure liquid chromatography (HPLC) method has been developed for the analysis of cefazolin in serum. Serum was deproteinized by the addition of 6% trichloroacetic acid and injected onto a reverse-phase column with a mobile phase of 10 to 15% methanol in 1% aqueous acetic acid. Cefazolin chromatographed without interference from ultraviolet-absorbing components of serum, with a retention time of 3.1 min. Standard curves comparing peak area with concentration prepared from dog or human sera were linear over a range of 1.6 to 200 μg/ml. Results from the HPLC assay were compared with microbiological assays (cylinder plate method) on both standard serum samples and sera from dogs and human subjects receiving intramuscular cefazolin. The HPLC method was somewhat more accurate in comparison with the microbiological assay performed on serum samples of known concentration. The comparison of results from an analysis of serum levels of dogs or human subjects receiving cefazolin indicated that the two methods would lead to identical conclusions concerning pharmacokinetics or the achievement of therapeutic serum levels. The HPLC assay method presents an alternative to conventional microbiological assays, with marked improvement in speed (30 min) and considerable potential for future development.
Comparative Penetration of Amikacin, Gentamicin, and Penicillin G into Exudate Fluid in Experimental Sterile Peritonitis
Authors: MacGregor Rob Roy
Published: June 2012

Using a rabbit sterile peritonitis model, we compared the penetration of intravenously administered amikacin, gentamicin, and penicillin G into peritoneal exudate. Peritonitis was induced with sterile normal saline, and the peritoneal exudate contained 23,751 ± 3,039 granulocytes 8 h later. Antibiotics were administered intravenously 3 h after initiating peritonitis, and serum and peritoneal fluid concentrations were measured for 5 h. Peritoneal levels of each antibiotic exceeded simultaneous serum levels by 1 h after dose and remained above serum levels thereafter. The maximum peritoneal fluid concentration of amikacin reached 71.2% ± 12.7 of the maximum serum concentration, whereas maximum gentamicin peritoneal concentration achieved 37.1% ± 2.7, and penicillin achieved 23.2% ± 4.5, of their respective maximum serum concentrations.
Rapid Method for Determining the Minimum Inhibitory Concentration of Ampicillin for
Haemophilus influenzae
Authors: Ryan Raymond , Tilton Richard C.
Published: June 2012

A rapid method for determining the minimal inhibition concentrations (MICs) of ampicillin using
Haemophilus influenzae
as the test organism is described. This semiautomated technique using the Autobac system was compared with the agar dilution MIC method. Fifty-seven isolates of both susceptible and resistant
H. influenzae
were tested. There was exact quantitative agreement with 65% of the isolates, and 91% of the isolates showed no more than a one-dilution-interval difference when MICs were determined by both methods. Total testing time was 3 to 4 h.
Antimicrobial Activity In Vitro of Netilmicin and Comparison with Sisomicin, Gentamicin, and Tobramycin
Authors: Meyers Burt R. , Hirschman Shalom Z.
Published: June 2012

The antimicrobial activity of netilmicin, a new semisynthetic aminoglycosidic aminocyclitol, was determined against 123 recent gram-negative clinical isolates susceptible to gentamicin and 60 isolates resistant to either sisomicin, gentamicin, or tobramycin. The minimal inhibitory concentrations and minimal bactericidal concentrations of netilmicin, sisomicin, gentamicin, and tobramycin against
Pseudomonas, Escherichia coli, Klebsiella, Enterobacter, Proteus mirabilis
, and indole-positive
Proteus
were, in general, quite similar. Gentamicin was the most active against
Serratia
. A total of 54, 67, and 88% of gentamicin-resistant
Pseudomonas, Serratia
, and
Klebsiella
, respectively, were susceptible to netilmicin. Strains of indole-positive
Proteus, Acinetobacter, Providencia
, and
E. coli
resistant to gentamicin were likely to be resistant also to netilmicin.
Beta-Lactamase Activity in Strains of
Bacteroides melaninogenicus
and
Bacteroides oralis
Authors: Salyers A. A. , Wong J. , Wilkins T. D.
Published: June 2012

β-Lactamase from strains of
Bacteroides melaninogenicus
and
Bacteroides oralis
hydrolyzed penicillin more rapidly than ampicillin or carbenicillin. Cephalothin and a chromogenic cephalosporin (87/312) were also hydrolyzed by the enzyme. Activity was found only in β-lactam-resistant strains, but there was considerable variation in activity among strains having the same minimal inhibitory concentrations of antibiotic. β-Lactamase activity was cell bound and appeared to be tightly associated with the cell envelope since detergents were required to elute this activity.
Nalidixic Acid-Induced Protein Alterations in
Escherichia coli
Authors: Chao Lee
Published: June 2012

The effect of nalidixic acid on pulse-labeled protein patterns was analyzed by sodium dodecyl sulfate-polyacrylamide slab gel electrophoresis. The drug was found to alter protein patterns in a drug-sensitive strain but not in the isogenic drug-resistant strain of
Escherichia coli
. The drug-induced alteration of protein patterns was demonstrated by the appearance of some and the disappearance of other pulse-labeled peptides elicited by the drug.
Effect of Atebrin on Bacterial Membrane Adenosine Triphosphatases in Relation to the Divalent Cation Used as Substrate and/or Activator
Authors: Carreira José , Muñoz Emilio
Published: June 2012

The action of atebrin on purified adenosine triphosphatase (ATPase) from
Micrococcus lysodeikticus
was studied as well as on the membrane-bound and soluble ATPases from
Escherichia coli
and
Bacillus megaterium
. Atebrin inhibited the Ca
2+
-dependent activity of all these enzymes, and the inhibition was reversed by an excess of Ca
2+
ions. Kinetic studies carried out with the purified enzyme from
M. lysodeikticus
showed that the inhibition by atebrin was strongly cooperative, suggesting the complex nature of the process. On the other hand, atebrin stimulated the Mg
2+
ATPase activity of the
M. lysodeikticus
enzyme, displacing its adenosine 5′-triphosphate (ATP)/Mg
2+
optimum ratios, but inhibited the Mg
2+
-ATPase activity of
E. coli
provided that ATP was in excess over Mg
2+
, i.e., that the ATP/Mg
2+
ratio was higher than its optimum. These results suggest that divalent cations influence the bacterial ATPases in different ways depending on the type of divalent ion and/or enzyme. The effect of atebrin on bacterial ATPases may reflect those differences, and its complex mechanism of action might be related to the existence of more than one site for divalent cations and/or distinct conformational states in these enzymes.
Emergence of Gentamicin-Resistant
Klebsiella
in a General Hospital
Authors: Rennie R. P. , Duncan I. B. R.
Published: June 2012

Gentamicin had been in use in a general hospital for over 7 years before any gentamicin-resistant
Klebsiella
were observed. In 1974 and 1975, nine different gentamicin-resistant serobiotypes of
Klebsiella
were isolated from 35 patients. The first strain to appear had R-factor-mediated gentamicin resistance, and it infected 19 patients during a period of almost 2 years, spreading largely by case-to-case infection in patients with urinary catheters. It appeared to lose the capacity to transfer its gentamicin resistance after it had infected five of the patients. We had previously isolated on the same ward a gentamicin-susceptible
Klebsiella
of identical type, and it was found to be capable of acquiring an R-factor for gentamicin resistance. All of the other types of gentamicin-resistant
Klebsiella
infected few patients and did not persist in the hospital; four of them had R-factor-mediated resistance to gentamicin and all four, as did the original strain, cotransferred kanamycin, neomycin, and tobramycin resistance. Every gentamicin-resistant
Klebsiella
was susceptible to amikacin and netilmicin.
Pharmacological and Clinical Study of Bacampicillin in Acute Peritonsillitis–a Comparison with Ampicillin
Authors: Hallander Hans O. , Flodström Anders , Sjövall Jan
Published: June 2012

The pharmacological and clinical properties of bacampicillin in three dosage groups were studied in 66 hospitalized patients with unilateral acute peritonsillitis in a comparison with ampicillin. Bacampicillin is a new semisynthetic aminopenicillin which is rapidly converted to ampicillin but is better absorbed. Both drugs were given orally. The mean individual peak serum levels achieved with 200, 400, and 800 mg of bacampicillin in the first morning dose were 4.9, 6.8, and 11.9 mg/liter, respectively, with an almost linear dose response. The peak level of 800 mg of bacampicillin was significantly higher than the 6.8 mg/liter noted after a nearly equimolar dose of 500 mg of ampicillin. A linear relationship was also seen between dose and area under the serum concentration-time curve. Preliminary antibiotic concentration studies in five patients indicated therapeutic levels in peritonsillar pus. Beta-streptococci alone or in combination with anaerobes were isolated from about half of the abscesses, whereas anaerobes were isolated from the other half. Treatment was supplemented by surgical procedures in the majority of cases. The clinical effect was good in all treatment groups, with only one relapse. All beta-streptococci were eliminated during therapy. The total number of gastrointestinal side effects was significantly lower in patients treated with bacampicillin, although the difference in frequency of diarrhea alone was not significant.
Prevention of 5-Fluorouracil-Caused Growth Inhibition in
Sordaria fimicola
Authors: Schoen Howard F. , Berech John
Published: June 2012

Growth (dry weight accumulation) of
Sordaria fimicola
in standing liquid culture (sucrose-nitrate-salts-vitamins) is inhibited by the presence of 5 μM 5-fluorouracil in the medium. This inhibition is completely prevented by uracil, deoxyuridine, and 5-bromouracil, partly prevented (40 to 90% of growth observed without 5-fluorouracil) by uridine, thymidine, and 5-bromodeoxyuridine, and slightly prevented by trifluorothymine, cytosine, cytidine, deoxycytidine, and 5-methylcytosine (all at 0.5 to 1 mM). Thymidine and thymine riboside were without any apparent effect. Growth is also inhibited by 0.2 mM 6-azauracil, and this inhibition was completely prevented by uracil and uridine, partly prevented by deoxyuridine, 5-bromouracil, cytidine, and 5-methylcytosine, and slightly prevented by thymine, thymidine, 5-bromodeoxyuridine, cytosine, and deoxycytidine. The data suggest that the observed inhibition of growth by 5-fluorouracil is due to inhibition of both ribonucleic acid and deoxyribonucleic acid synthesis. The data also allow inferences concerning pyrimidine interconversions in
S. fimicola;
i.e., thymine can be anabolized to thymidylic acid without first being demethylated, although demethylation appears to occur also.
Evaluation of the Performance Parameters of a Prediluted, Quantitative Antibiotic Susceptibility Test Device
Authors: Tilton Richard C. , Isenberg Henry D.
Published: June 2012

A multiwelled plastic strip containing prediluted antibiotics was tested. Antibiotics available at the time of testing included ampicillin, penicillin, methicillin, erythromycin, clindamycin, tetracycline, and minocycline. The effects of inoculum size, inoculum volume, temperature, and time of incubation were determined. A limited clinical evaluation using laboratory strains of selected bacteria proved this product to be a rapid, economical, and reliable method for the determination of the minimal inhibitory concentration of antibiotics.
Tetracycline Inhibits Propagation of Deoxyribonucleic Acid Replication and Alters Membrane Properties
Authors: Pato Martin L.
Published: June 2012

Tetracycline, at concentrations greater than required for inhibition of protein synthesis, rapidly and completely inhibits replication of deoxyribonucleic acid (DNA) in
Escherichia coli
and
Bacillus subtilis
. At these concentrations of tetracycline, synthesis of ribonucleic acid is not appreciably altered. In addition to inhibiting DNA replication, tetracycline causes alterations of the cytoplasmic membrane resulting in leakage of intracellular pools of nucleotides, amino acids, and the non-metabolizable sugar analogue, thiomethylgalactoside. As DNA is synthesized at a site on the membrane, alterations of membrane structure by tetracycline may be responsible for the observed inhibition of DNA replication.
Bioassay for Miconazole
Authors: Espinel-Ingroff Ana , Shadomy S. , Fisher John F.
Published: June 2012

A radial diffusion bioassay for miconazole, which employs
Candida stellatoidea
as the indicator organism, is described. Results from three patients treated with the drug are presented.
Cairomycin B, a New Antibiotic
Authors: Shimi Ibrahim R. , Abedallah Nadia , Fathy Shadia
Published: June 2012

Cairomycin B is a new cyclic peptide antibiotic that was isolated from
Streptomyces
As-C-19 obtained from the soil of Cairo. The antibiotic had the following empirical formula: C
10
H
15
N
3
O
3
; on acid hydrolysis, it yielded aspartic acid and lysine. Spectral analysis and its chemical characteristics indicated that it was a cyclic peptide. The antibiotic melted at 120 to 121°C and was freely soluble in chloroform, ethyl acetate, and acetone, slightly soluble in alcohols, and rather insoluble in water and petroleum ether. Cairomycin B was mainly active against gram-positive bacteria, with high toxicity to experimental animals and weak serum-binding properties.
Plasmid-Mediated Chloramphenicol Resistance in
Haemophilus influenzae
Authors: Van Klingeren B. , Van Embden J. D. A. , Dessens-Kroon M.
Published: June 2012

A clinical isolate of
Haemophilus influenzae
HC234 was found to be resistant to chloramphenicol and tetracycline. It was shown that both resistance markers are tranferable as one unit to other
Haemophilus influenzae
strains and also to
Escherichia coli
. Data are presented which indicate that conjugation is the most likely mechanism of resistance transfer. HC234 was shown to carry a single plasmid species with a molecular weight of 38 × 10
6
.
Changing Patterns of Plasmid-Mediated Drug Resistance During Tetracycline Therapy
Authors: Møller J. K. , Bak A. Leth , Stenderup A. , Zachariae H. , Afzelius H.
Published: June 2012

The patterns of drug resistance and the frequency of conjugative R plasmids in intestinal
Escherichia coli
from 88 patients treated for a skin disease (
acne vulgaris
) with low oral doses of tetracycline are reported. The proportion of patients with resistant bacteria was progressively greater in patients who received tetracycline for 1 week, 4 weeks, or longer (from 50 to 88%). No multiply drug-resistant bacteria were detected before treatment or after 1 week of treatment. After more than 4 weeks of treatment, multiply drug-resistant
E. coli
were isolated from about 50% of the patients. The origin and selection of R plasmid-determined multiple drug resistance are discussed.
Antibacterial Activity of Netilmicin, a New Aminoglycoside Antibiotic, Compared with That of Gentamicin
Authors: Phillips Ian , Smith Anne , Shannon Kevin
Published: June 2012

The antibacterial activity of netilmicin (Sch 20569), a new semisynthetic aminoglycoside, was compared with that of gentamicin against a variety of gram-negative bacteria, staphylococci, and streptococci. Both antibiotics had similar activity against most organisms, but netilmicin had appreciably greater activity against gram-negative organisms that were resistant to gentamicin because these species synthesized aminoglycoside 3-
N
-acetyltransferase I or aminoglycoside 2″-
O
-nucleotidyltransferase. Netilmicin was also more active than gentamicin against gentamicin-resistant strains of
Staphylococcus aureus
that produced two enzymes–aminoglycoside-2″-
O
-phosphotransferase and aminoglycoside-6′-
N
-acetyltransferase.
Microbial Formation of 4-Thiouracil
Authors: Dolak L. , Sokolski W. T. , Mizsak S. , Stroman D. W. , Sebek O. K.
Published: June 2012

A soil organism identified as
Streptomyces libani
var.
soldani
was found to produce 4-thiouracil. The product was isolated in a yield of 150 μg/ml of filtered beer and characterized by C-13 magnetic resonance and high-resolution mass spectroscopy. The product has a broad antibacterial spectrum but low specific activity.
Effect of Antibiotics on Chemotaxis of Human Leukocytes
Authors: Forsgren Arne , Schmeling David
Published: June 2012

The effect of 20 different antibiotics on chemotaxis by human neutrophils was studied. Human leukocytes incubated with chloramphenicol, rifampin, sodium fusidate, and tetracyclines in vitro showed markedly depressed migration. The mechanisms by which these antibiotics affect leukotaxis are discussed.
Penetration of Cefazolin, Cephaloridine, and Cefamandole into Interstitial Fluid in Rabbits
Authors: Carbon Claude , Contrepois Alain , Brion Nils , Lamotte-Barrillon Suzanne
Published: June 2012

We compared the penetration of three cephalosporins into interstitial fluid. Interstitial fluid was obtained in rabbits from Silastic tissue cages. Cefazolin, cephaloridine, and cefamandole were administered by the intramuscular route (30 mg/kg per injection). Peak blood levels and interstitial concentrations were studied after a single injection. Interstitial levels were also compared in a three-injection study (one injection every 12 h) and in a cumulative effect study (six injections), in which the interval between injections was established for each drug on the basis of its common therapeutic use. After a single injection, cephaloridine activity was detected more rapidly and attained higher levels than the other two drugs within the first 4 h. However, 2 h after the third injection, cefazolin levels in tissue fluid were higher than with cephaloridine. Cefamandole consistently gave the lowest interstitial levels. With all three drugs, detectable concentrations were present in interstitial fluid at a time when no detectable antibiotic was found in serum. In the six-injection study, the interstitial levels obtained with cefazolin were significantly higher than those observed with the other drugs. Our data suggest that cefazolin is a drug of choice due to its high extravascular levels.
Growth Inhibition of
Escherichia coli
W by
d
-Norvalyl-
d
-Alanine: an Analogue of
d
-Alanine in Position 4 of the Peptide Subunit of Peptidoglycan
Authors: Neuhaus F. C. , Goyer S. , Neuhaus D. W.
Published: June 2012

Position 4 analogues of
d
-alanine in the peptide subunit of uridine 5′-diphosphate-
N
-acetylmuramyl-Ala
1
-
d
Glu
2
- Lys
3
-
d
Ala
4
-
d
Ala
5
have a significant inhibitory effect on penicillin-sensitive peptidoglycan synthesis in
Gaffkya homari
(C. V. Carpenter, S. Goyer, and F. C. Neuhaus, 1976). The specificity profile of this in vitro system has been used as a basis for designing analogues with potential antibacterial activity. To circumvent the specificity determinants exerted by
d
-alanine:
d
-alanine ligase (adenosine 5′-diphosphate), attention was directed to
dd
-dipeptides of the type
d
-alanyl-analogue-
d
-alanine as a method for incorporating analogues into position 4 of the peptide subunit in vivo. Of the three dipeptides,
d
Abu-
d
Ala,
d
Nva-
d
Ala, and
d
Val-
d
Ala, only
d
Nva-
d
Ala (5 × 10
−4
M) inhibited the growth of
Escherichia coli
W in the presence of 5 × 10
−6
M
d
-cycloserine. This concentration of
d
-cycloserine did not inhibit growth, but it potentiated the bactericidal activity of the dipeptide. The lack of antibacterial activity observed with
d
Abu-
d
Ala and
d
Val-
d
Ala was correlated with the poor ability of these dipeptides to be taken up via the dipeptide transport system of this organism. Prevention of lysis induced by
d
Nva-
d
Ala plus
d
-cycloserine by certain dipeptides and not by others supported this correlation. It is proposed that the
d
-norvalyl residue of the dipeptide is incorporated in vivo into position 4 of the peptide subunit of peptidoglycan, and that this subunit is not an effective substrate in the reaction(s) catalyzed by the penicillin-susceptible enzyme(s) of cross-linked peptidoglycan synthesis.
Indirect Mouse Model for the Evaluation of Potential Antiviral Compounds: Results with Venezuelan Equine Encephalomyelitis Virus
Authors: Kuehne Ralph W. , Pannier Wallace L. , Stephen Edward L.
Published: June 2012

An indirect mouse model was utilized to evaluate the antiviral activity of several compounds against Venezuelan equine encephalomyelitis (VEE) virus infection in mice. Mice were given various dosages of lysine-stabilized polyriboinosinic acid-polyribocytidylic acid, a tilorone analogue, kethoxal, or mepacrine before and/or shortly after receiving one of several dose levels of attenuated strain TC-83 VEE virus. Twenty-one days later, the same mice were rechallenged intracranially with virulent Trinidad donkey strain VEE virus. Susceptibility to rechallenge was interpreted as evidence of drug effectiveness in completely preventing the initial immunizing virus infection. In contrast, if a drug lacked antiviral effectiveness, the initial attenuated infection stimulated sufficient immunity to protect mice against the virulent rechallenge. Both of the interferon inducers, lysine-stabilized polyriboinosinic acid-polyribocytidylic acid and tilorone analogue 11,567, possessed significant (
P
< 0.01) antiviral activity based upon this indirect model, whereas mepacrine and kethoxal were inactive. Results using the indirect method were confirmed by using the conventional direct method for evaluating the effectiveness of potentially useful antiviral compounds. The indirect mouse model described should prove useful for studying drug efficacy against certain viruses that are lethal only by intracranial inoculation.
Susceptibility of
Clostridium perfringens
Isolated from Human Infections to Twenty Antibiotics
Authors: Schwartzman Joseph D. , Reller L. Barth , Wang Wen-Lan L.
Published: June 2012

The proper choice of antibiotic for
Clostridium perfringens
infections in patients allergic to penicillin is not clear; the usual recommendations and recent in vitro studies disagree. We tested the susceptibility of 57 strains of
C. perfringens
to eight penicillins, seven cephalosporins, two tetracyclines, clindamycin, chloramphenicol, and rifampin by the agar dilution method. All strains were inhibited by (per milliliter) 4 μg or less of any of the penicillins, chloramphenicol, or clindamycin and 8 μg or less of any of the cephalosporins tested. Penicillin G and amoxicillin inhibited all strains at 0.12 μg or less per ml. Only 54% of the strains were inhibited by 1 μg of tetracycline per ml. Penicillin G remains the drug of first choice for infections with
C. perfringens
; it need not be added to a regimen containing a penicillinase-resistant penicillin given parenterally in high doses. The cephalosporins should be considered as alternative drugs for penicillin-allergic patients. Clindamycin and chloramphenicol are also effective. Tetracyclines cannot be depended upon in clostridial infections without in vitro testing, which is impracticable for initial empirical therapy.