bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a Commercial Microdilution System for Quantitative Susceptibility Testing of Aminoglycosides Against Multidrug-Resistant, Gram-Negative Bacilli
Authors: Peterson Lance R. , Gerding Dale N. , Johnson Margaret M. , Cherne John E. , Opfer Bonnie J. , Hall Wendell H.
Published: June 2012

Susceptibility of clinical isolates of
Pseudomonas aeruginosa
(29 isolates),
Klebsiella
species (54 isolates),
Escherichia coli
(28 isolates),
Serratia marcescens
(28 isolates), and
Enterobacter
species (29 isolates) to gentamicin, tobramycin, and amikacin was determined by the following three methods: commercial broth microdilution trays, standard agar dilution, and disk diffusion susceptibility. A total of 504 tests were performed by each method, and overall susceptibility or resistance determined by the broth microdilution method agreed with that determined by the agar dilution method in 92.7% of the tests, whereas results from the disk diffusion method agreed with those from the agar dilution method in 91.9% of the tests. The broth microdilution and disk diffusion methods agreed with each other 88.7% of the time. The broth microdilution system results varied from the agar dilution method results by more than one dilution in 121 of 504 determinations (24%); however, this altered susceptibility determinations in only 7.3% of the assays.
E. coli
isolates were found to be quantitatively more resistant to the aminoglycosides with the broth microdilution method than with the agar dilution method. In contrast, the broth microdilution method demonstrated
P. aeruginosa
to be quantitatively more susceptible to the aminoglycosides than when the results were obtained by the agar dilution method. The Micro-Media Systems method is economical, reliable, rapid, and simple to perform and yields quantitative minimum inhibitory concentrations.
Evidence of plasmid-mediated production of aminoglycoside-modifying enzymes not previously described in Acinetobacter
Authors: Murray B E , Moellering R C
Published: June 2012

Two blood culture isolates of Acinetobacter calcoaceticus subsp. anitratus (Herellea vaginicola) were recently observed to be unusually resistant to aminoglycosides. Each strain was found to contain aminoglycoside-modifying enzymes which have not been described previously in this species, including 2"-adenylyltransferase, 3"-adenylyltransferase, 3'-phosphotransferase-III, and 3-acetyltransferase. Treatment of one strain (H-S) with novobiocin led to a loss of resistance to multiple antimicrobial agents and a loss of two aminoglycoside-modifying enzymes; agarose gel electrophoresis of lysates of this strain revealed that the loss of resistance markers was associated with the loss of a large-molecular-weight plasmid. Treatment of the second strain (H-D) with novobiocin produced derivative strains with three different resistance patterns. Agarose gel electrophoresis of deoxyribonucleic acid from crude lysates and from cesium chloride-ethidium bromide gradients of this strain showed only a small plasmid (molecular weight, 5 X 10(6)) common to all variants and failed to explain the loss of resistance markers.
Comparison of cotrimoxazole, ampicillin, and chloramphenicol in treatment of experimental Haemophilus influenzae type B meningitis
Authors: Perfect J R , Lang S D , Durack D T
Published: June 2012

To evaluate cotrimoxazole in the treatment of bacterial meningitis, we compared its action with that of ampicillin and chloramphenicol in experimental Haemophilus influenzae type b meningitis. Both trimethoprim and sulfamethoxazole penetrated well into the cerebrospinal fluid of infected rabbits, reaching 40 and 26%, respectively, of their simultaneous serum levels. Levels measured 30 and 60 min after intravenous injection exceeded the minimum inhibitory concentration of this combination for H. influenzae by 10- to 100-fold. The mean ratio of trimethoprim to sulfamethoxazole in cerebrospinal fluid was 1:22. Cotrimoxazole was as effective as ampicillin in therapy of beta-lactamase-negative H. influenzae meningitis and as effective as chloramphenicol for a beta-lactamase positive strain. These findings corroborate favorable preliminary clinical experience reported by others and indicate that cotrimoxazole deserves further study in the therapy of bacterial meningitis.
Pharmacological and in vitro evaluation of cyclacillin: assessment as potential single-dose therapy for treatment of Neisseria gonorrhoeae infection
Authors: Wagner K F , Blair A D , Counts G W , Holmes K K
Published: June 2012

The pharmacokinetic properties of cyclacillin administered as a 3.0-g oral dose, with and without progenecid, have been studied and correlated with in vitro activity of the drug against 109 isolates of Neisseria gonorrhoeae. By 8 h after dosage, levels of cyclacillin in serum declined below the minimal inhibitory concentration and the inferior antibacterial activity of cyclacillin (compared with that of amipicillin) suggest that cyclacillin is not a promising alternative to ampicillin for single-dose treatment of gonorrhea.
Hydrolysis of 3-acetoxymethyl cephalosporins by lysed whole blood
Authors: Wright W E , Frogge J A
Published: June 2012

Cephalosporins having a 3-acetoxymethyl group are hydrolyzed to the corresponding desacetyl derivative by lysed whole blood but not by plasma or serum. When bioassays for this important class of cephalosporins must be run in whole blood or on tissues containing whole blood, steps should be taken to assure that the influence of the whole blood on the bioassay is properly interpreted.
Biosynthesis of peptidoglycan in Pseudomonas aeruginosa: comparison of the inhibitory effects of cefotaxime, its anti isomer, and the syn S-oxide compound
Authors: Mirelman D , Nuchamowitz Y
Published: June 2012

The intrinsic effect of three novel methoxyimino derivatives of cephalosporin (cefotaxime [syn HR 756]; its anti isomer, R 02 5328 A; and the syn S-oxide derivative, HR 109) on the biosynthesis of peptidoglycan of Pseudomonas aeruginosa X-48 was investigated. Cefotaxime at very low concentrations (50% inhibition at 0.025 microgram/ml) inhibited the transpeptidase reaction which catalyzes the incorporation and attachment of newly synthesized peptidoglycan to the preexisting cell wall sacculus. The S-oxide compound, HR 109, was a much less efficient inhibitor of this reaction (50% inhibition at 0.55 microgram/ml), whereas the anti isomer of cefotaxime, R 02 5328 A, had no inhibitory effect. All three compounds were quite similar in being relatively poor inhibitors of D-alanine carboxypeptidase.
Isoniazid interaction with tyrosine as a possible mode of action of the drug in mycobacteria
Authors: Herman R P , Weber M M
Published: June 2012

The antitubercular drug isoniazid (INH) was hown by radio-chromatographic studies to react with tyrosine in growth medium. Exogenous tyrosine added to the growth medium interfered with the inhibitory action of INH on Mycobacterium phlei. These observations were confirmed by difference spectra studies which showed that tyrosine would react with INH as long as the tyrosine phenolic hydroxyl group was not blocked. These results led to the hypothesis that INH could exert its influence by interfering with tyrosine residues in mycobacterial proteins. N-acetylimidazole, a tyrosine-acetylating agent, mimicked the action of INH on the reduced nicotinamide adenine dinucleotide oxidase and dehydrogenase activity in electron transport particles from wild-type and INH-resistant M. phlei. Pyrazinamide, a drug structurally related to INH, also mimicked its effect on electron transport particles. To confirm that INH could react with tyrosine in proteins, purified enzymes with known tyrosine positions were tested. Bovine carboxypeptidase A with tyrosine at the active site was inhibited by INH and N-acetylimidazole, whereas the controls, yeast alcohol dehydrogenase and ribonuclease A, were not. It is therefore proposed that tyrosine residues in proteins may serve as the target for INH action in mycobacteria.
Serum and Subcutaneous Chamber Fluid Dynamics of Penicillins After Single Large Parenteral Doses
Authors: Tight Robert R. , White Arthur C.
Published: June 2012

Serum and subcutaneous chamber fluid (CF) dynamics of penicillin G, ampicillin, and amoxicillin were studied in rabbits after single large parenteral doses comparable to doses used in treating gonorrhea and endocarditis. The effects of parenteral probenecid and of injection of an antibiotic directly into a subcutaneous chamber (“intrachamber” injection) also were studied. Peak serum antibiotic concentrations exceeded peak CF concentrations and occurred sooner. Antimicrobial activity persisted longer in CF than in serum. Percent penetration [100 × (CF peak/serum peak)] of CF was least after intramuscular ampicillin and amoxicillin, was greatest after intrachamber ampicillin and intrąmuscular aqueous procaine penicillin G, and was related to duration of antibiotic concentration gradients from serum to CF. Intramuscular aqueous crystalline penicillin G resulted in higher serum and CF penicillin G concentrations than intramuscular aqueous procaine penicillin G, which prolonged the duration of penicillin G in serum and CF. Amoxicillin diffused into CF more readily than ampicillin. Probenecid resulted in higher early serum and CF antibiotic concentrations, but had little or no effect on duration of antibiotic activity. Intrachamber ampicillin resulted in more prolonged serum and CF ampicillin activity than intramuscular ampicillin, but much lower peak serum concentrations. The data suggest a possible means by which probenecid improves the efficacy of gonorrhea therapy with aqueous procaine penicillin G. Intrachamber administration of penicillins could be useful in treating experimental infections requiring prolonged therapy.
Lethal Effect of a Heterologous Murein Hydrolase on Penicillin-Treated
Streptococcus sanguis
Authors: Horne Diane , Tomasz Alexander
Published: June 2012

Nine strains of
Streptococcus sanguis
exhibited tolerance to benzylpenicillin: the growth of each strain was susceptible to penicillin with minimal inhibitory concentrations of 0.1 μg/ml or lower, but the bacteriolytic and bactericidal effects were limited in each case. The tolerance of these bacteria was also reflected in the large discrepancies between the minimal inhibitory and minimal bactericidal concentrations for benzylpenicillin. The hypothesis that a natural deficiency of endogenous murein hydrolase (autolysin) in this species accounts for the penicillin tolerance was tested by using a heterologous murein hydrolase, the C-phage-associated lysin. In seven of the strains, addition of the lysin to the culture together with penicillin or other cell wall inhibitors resulted in lysis and rapid loss of viability. The enzyme alone did not appreciably affect normally growing cultures. The irreversible effects of penicillin plus lysin were drastically reduced in the presence of the bacteriostatic agents chloramphenicol and cerulenin. Speculations based on experiments are presented for the mechanisms by which penicillin treatment sensitizes these bacteria to an exogenous lytic enzyme. Similar phenomena requiring cooperation of host factors and penicillin may occur during infection, since somewhat similar although less pronounced results were obtained by addition of human lysozyme to penicillin-treated
S. sanguis
.
Treatment of experimental Haemophilus influenzae type b meningitis with 1-oxa-beta-lactam (LY127935)
Authors: Cordera C S , Pekarek R S
Published: June 2012

1-Oxa-beta-lactam (LY127935) (Shionogi 6059-S) is a new type beta-lactam antibiotic having a broad spectrum of antibacterial activity. It is highly active against ampicillin-resistant strains of Haemophilus influenzae exhibiting minimal inhibitory concentrations as low as 0.06 microgram/ml. This compound also has the ability to penetrate into the cerebrospinal fluid of both normal and infected infant rats and attains approximately 10% of the corresponding blood levels. LY127935 was evaluated for its ability to treat ampicillin-resistant H. influenzae meningitis in an established experimental model using infant rats. Rats with ampicillin-resistant H. influenzae meningitis were treated subcutaneously three times daily for 2 days with various dose levels of LY127935. When given in doses as low as 10 mg/kg, LY127935 sterilized the blood and cerebrospinal fluid in all rats examined at 1 and 5 days posttreatment. In contrast, ampicillin was not effective at this dose in eliminating H. influenzae from the blood and cerebrospinal fluid of infected rats. LY127935 was effective against experimental ampicillin-resistant H. influenzae meningitis in the dosages employed.
Effect of trimethoprim and trimethoprim-sulfamethoxazole on development of drug-resistant vaginal and fecal floras
Authors: Pancoast S J , Hyams D M , Neu H C
Published: June 2012

Trimethoprim-sulfamethoxazole (TMP-SMX) or trimethoprim (TMP) alone was given on a random double-blind basis to 26 young women to treat urinary tract infections. Fecal and introital aerobic bacterial floras were identified at 1, 7, 14, and 42 days to analyze changes in these floras or development of resistance to TMP or TM-SMX. Neither TMP alone nor the TMP-SMX combination administered for 2 weeks selected a resistant fecal or introital flora. In the few individuals who had strains resistant to TMP or TMP-SMX before initiation of therapy, these organisms did not persist once therapy began. Both programs effectively cleared the introitus and rectal areas of Enterobacteriaceae. Concentrations of TMP adequate to inhibit the majority of Escherichia coli strains causing urinary tract infections were found in the vaginal secretions.
UK31214, a new aminoglycoside and derivative of kanamycin B
Authors: Wise R , Andrews J M , Bedford K A
Published: June 2012

The in vitro activity of UK31214, a kanamycin B derivative, was studied against 250 recent isolates and compared with other aminoglycosides. Against the Enterobacteriaceae (with the exception of Proteus mirabilis and Providencia stuartii) UK31214 and amikacin had similar degrees of activity (mode minimum inhibitory concentration [MIC], 1 microgram/ml). Proteus mirabilis and P. stuartii strains were four- to eight-fold more susceptible to amikacin than to UK31214. Pseudomonas aeruginosa strains were equally susceptible to both amikacin and UK31214 (mode MIC, 4 microgram/ml), but tobramycin was the most active antimicrobial agent tested (mode MIC, 0.25 microgram/ml). The gentamicin-resistant strains of P. aeruginosa were equally susceptible to UK31214 and amikacin. Strains of Staphylococcus aureus were more susceptible to gentamicin or tobramycin than to UK31214 or amikacin (mode MIC, 0.5 microgram/ml). A synergistic interaction between UK31214 and carbenicillin was demonstrated.
Moxalactam (6059-S), a Novel 1-Oxa-β-Lactam with an Expanded Antibacterial Spectrum: Laboratory Evaluation
Authors: Yoshida Tadashi , Matsuura Shinzō , Mayama Mikao , Kameda Yasuo , Kuwahara Shōgo
Published: June 2012

Moxalactam (6059-S) {7β-[2-carboxy-2-(4-hydroxyphenyl)acetamido]-7α-methoxy-3-[[(1-methyl-1H-tetrazol-5-yl)thio]-methyl]-1-oxa-1-dethia-3-cephem-4- carboxylic acid disodium salt} is a new semisynthetic 1-oxa-β-lactam derivative for parenteral use. It was highly active against a broad range of gram-negative microorganisms, including those resistant to other cephalosporins. Moreover, it had widely expanded antibacterial spectra which included
Haemophilus influenzae
, indole-positive
Proteus, Enterobacter, Serratia marcescens, Pseudomonas aeruginosa
, and
Bacteroides fragilis
. When a large number of clinical isolates of the above-named bacilli were tested by the agar dilution method, using an inoculum size of one loopful of 10
6
or 10
8
organisms or both per ml, the 70% minimal inhibitory concentrations at the lower inoculum were 0.2, 0.2, 0.4, 0.8, 25, and 0.8 μg/ml, respectively. Its activity appeared to be independent of inoculum size and addition of serum. In these organisms, morphological response of the exposed cells revealed that the bacteriolytic effect of 6059-S was initiated by a concentration equivalent to the minimal inhibitory concentration. 6059-S was markedly bactericidal to both β-lactamase-producing and -nonproducing strains of
Escherichia coli
; this was well reflected by its extraordinary stability to microbial β-lactamase degradation. Administered subcutaneously in mice, 6059-S attained plasma levels and a half-life similar to those of cefazolin and exhibited potent protective efficacy against systemic infections; it also proved to be significantly more effective than either sulbenicillin or piperacillin against
Pseudomonas aeruginosa
and than either cefazolin or cefmetazole against a variety of other gram-negative bacteria.
Moxalactam (6059-S), a new 1-oxa-beta-lactam: binding affinity for penicillin-binding proteins of Escherichia coli K-12
Authors: Komatsu Y , Nishikawa T
Published: June 2012

Moxalactam (6059-S) is a new beta-lactam derivative with a structure markedly different from those of penicillins or cephalosporins. The binding activity of 6059-S to penicillin-binding proteins (PBPs) in Escherichia coli K-12 was tested. [14C]benzylpenicillin- or [14C]6059-S-bound inner membrane proteins of E. coli K-12 were rapidly detected without using fluorography. 6059-S had the highest affinity for PBP-3 and -7/8, had a higher affinity than benzylpenicillin for PBP-1A, -1Bs, -4, and -5/6 and a lower affinity for PBP-2, 609134, the 1-thiacephem analog of 6059-S, showed as high an affinity for PBP-1A, -1Bs, -3, and -4 as 6059-S but a lower affinity for PBP-5/6.
In vitro and in vivo antimicrobial activities of sporaricin A, a new aminoglycoside
Authors: Kobayashi F , Saino Y , Koshi T , Hattori Y
Published: June 2012

The in vitro and in vivo antimicrobial activity of sporaricin A, a new aminoglycoside, was compared with that of amikacin, dibekacin, and gentamicin. Sporaricin A showed a broad spectrum of activity against various gram-positive and -negative bacteria, including amikacin-, dibekacin-, or gentamicin-resistant strains. Sporaricin A inhibited more than 90% of clinical isolates of staphylococci, Klebsiella, Enterobacter, Citrobacter, Serratia, and Proteus, except for P. morganii and P. inconstans, at the concentration of 3.13 microgram/ml. This activity, except for that against Serratia, was similar to that of amikacin. Against P. inconstans and S. marcescens, sporaricin A was more effective than amikacin, dibekacin, and gentamicin. However, its activity against Pseudomonas aeruginosa was relatively weak in comparison with three other aminoglycosides. Sporaricin A was highly effective against bacteria that had various aminoglycoside-inactivating enzymes and that were resistant to the other drugs tested, but it was not active against those with aminoglycoside 3-acetyltransferase-I. The activity of sporaricin A tended to be greater with a reduction in inoculum size of bacteria and an increase in medium pH and decreased slightly in the presence of 10 to 50% horse serum. The in vitro activity was confirmed by in vivo tests in experimental infections with various bacteria. Its protective effect seemed to be equal to or greater than that of amikacin or dibekacin.
Pharmacokinetics of Azlocillin in Subjects with Normal and Impaired Renal Function
Authors: Leroy A. , Humbert G. , Godin M. , Fillastre J. P.
Published: June 2012

The pharmacokinetics of azlocillin were investigated in five healthy subjects and in 16 subjects with chronic renal failure. After intravenous bolus injection of a single dose of 30 mg/kg in normal subjects, pharmacokinetic data were calculated, using a two-compartment open body model. The mean distribution serum half-life (T
1/2α
) was 0.11 h, and the mean elimination serum half-life (T
1/2β
) was 0.89 h. The volume of the central compartment (

V
C

) was 7.36 liters/1.73 m
2
, and the apparent volume of distribution (
V
dss
) was 14.15 liters/1.73 m
2
, i.e., 21.9% of body weight. The T
1/2β
after a 30-min intravenous infusion of 80 mg/kg to the same healthy subjects was 1.11 h. Serum clearances (

C
S

) for the 30- and 80-mg/kg doses were 215.0 and 152.9 ml/min per 1.73 m
2
. The mean renal clearances (

C
R

) were 145.2 and 94.1 ml/min per 1.73 m
2
for the respective doses. Between 61.8 and 69.6% of the injected dose was recovered in urine during the first 24 h. The elimination half-life in subjects with chronic renal impairment increased with the degree of renal insufficiency. After a 30-min intravenous infusion of 80 mg/kg the T
1/2β
values were 2.03, 4.01, and 5.66 h with creatinine clearances (
C
cr
) within 30 to 50, 10 to 30, and <10 ml/min per 1.73 m
2
, respectively. Urinary elimination was inversely related to the degree of renal impairment. In four patients out of and on a 6-h hemodialysis session mean elimination half-life values were 6.53 and 2.81 h, respectively. The fraction of drug removed by dialysis was 45.8%. The linear relationships between the elimination of half-life (T
1/2β
) and serum creatinine and the elimination rate constant (β) and creatinine clearance (
C
cr
) provided a basis for adjustment of dosage in renal failure.
Purification and properties of a new beta-lactamase from Pseudomonas cepacia
Authors: Hirai K , Iyobe S , Inoue M , Mitsuhashi S
Published: June 2012

An inducible beta-lactamase was purified from a beta-lactam antibiotic-resistant strain (GN11164) of Pseudomonas cepacia. The purified enzyme preparation gave a single protein band on polyacrylamide gel electrophoresis. The specific enzyme activity for the hydrolysis of cephalothin as a substrate was 314.5 U/mg of protein. The optimal pH was about 8.0, and the optimal temperature was 45 degrees C. The isoelectric point was 9.3, and the molecular weight was estimated to be about 22,000 to 24,000 from gel filtration on a Sephadex G-200 column and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme activity was inhibited by iodine, p-chloromercuribenzoate, clavulanic acid, CP 45899, and cloxacillin. The beta-lactamase showed a unique substrate profile by hydrolyzing most of the cephalosporins, including cefuroxime, cefotaxime (HR 756), ampicillin, and penicillin G, at a high rate.
Comparative in vitro activities of cefotaxime and ceftizoxime (FK749): new cephalosporins with exceptional potency
Authors: Greenwood D , Pearson N , Eley A , O'Grady F
Published: June 2012

Cefotaxime and its desacetoxymethyl derivative, ceftizoxime (previously known as FK749), are both extremely active against a wide spectrum of bacteria. In the present comparative study, the activity of ceftizoxime exceeded that of cefotaxime by a factor of four or more for strains of Klebsiella, Enterobacter, Providencia, Serratia, and Bacteroides; the only species for which the activity of cefotaxime exceeded that of ceftizoxime by a factor of four was Vibrio cholerae. Against other species, the activity of the two drugs was roughly comparable. Both showed outstanding activity against Haemophilus influenzae and Neisseria gonorrhoeae. Comparative turbidimetric and morphological studies revealed that ceftizoxime was able to induce spheroplast formation and rapid lysis in Escherichia coli strains at lower concentrations than cefotaxime. This difference was not found, however, when E. coli strains resistant to ampicillin by an intrinsic (nonenzymic) mechanism were tested.
Pharmacokinetics and bacteriological efficacy of moxalactam (LY127935), netilmicin, and ampicillin in experimental gram-negative enteric bacillary meningitis
Authors: Schaad U B , McCracken G H , Loock C A , Thomas M L
Published: June 2012

Moxalactam (LY127935) is a 1-oxa-beta-lactam which was active in vitro against the majority of 128 strains of gram-negative enteric bacilli isolated from meningitis in neonates. Pharmacokinetics and bacteriological efficacy of LY127935 were studied in a lapin meningitis model. The average penetration of this investigational oxa-cephalosporin into cerebrospinal fluid of infected rabbits was 23% compared with 25% for netilmicin and 11% for ampicillin. The cerebrospinal fluid concentrations of LY127935 produced median bactericidal titers of 1:64 to 1:128 against five coliform organisms (two Escherichia coli K1 strains, Klebsiella pneumoniae, Salmonella saint-paul, and Citrobacter diversus) used in these experiments compared with median titers of 1:2 to 1:8 for netilmicin and 1:2 to 1:4 for ampicillin. LY127935 was statistically significantly more effective than netilmicin or ampicillin in reducing cerebrospinal fluid bacterial colony counts and in sterilizing cerebrospinal fluid of experimentally infected rabbits. These results suggest that LY127935 has theoretical advantages over netilmicin and ampicillin for therapy of gram-negative bacillary meningitis.
Resistance to adriamycin cytotoxicity among respiratory-deficient mutants in yeast
Authors: Hixon S C , Ocak A , Thomas J E , Daugherty J P
Published: June 2012

Saccharomyces cell uptake of Adriamycin and the ensuing cytotoxic response were found to be dependent upon the ionic strength of the medium used for drug treatment. A given concentration of Adriamycin which inhibited growth in complete medium ws found to be significantly cytotoxic when administered in water. Many survivors after Adriamycin treatment in water were found to be respiratory-deficient petite mutants containing mitochondrial deoxyribonucleic acid mutations. Petite mutants arising after Adriamycin treatment were not induced but selected from the preexisting population of spontaneously derived petite mutants (normal frequency, 2%) due to an increased resistance of these mutants to killing by Adriamycin as compared with normal respiratory-sufficient cells. The responses to Adriamycin in mitochondrial deoxyribonucleic acid respiratory-deficient mutants (rho-, rho degrees, mit-) with different impaired mitochondrial functions was studied. All were similarly more resistant to killing by Adriamycin than wild-type cells. The common deficiency shared by these mutants, i.e., nonfunctioning electron transport, may play a role in protecting these mutants from Adriamycin cytotoxicity. In addition, normal cells grown on glycerol, requiring aerobic respiration for carbon source utilization were more susceptible to killing by Adriamycin than cells grown on glucose. These studies suggest that a mitochndrial function in yeast may interact with Adriamycin to potentiate a cell cytotoxic mechanism of the drug.
Experimental respiratory tract infection with Klebsiella pneumoniae DT-S in mice: chemotherapy with kanamycin
Authors: Nishi T , Tsuchiya K
Published: June 2012

Such factors as suspending medium, operating pressure, exposure time, inoculum size, and strain, sex, age, and weight of the animals were examined for their effects on the development of respiratory tract infection with Klebsiella pneumoniae DT-S in mice. The suspending medium was one of the most important factors. Aerosol challenge with a 10(9) colony-forming units per ml resulted in deposition of 10(4) colony-forming units of the organisms in the lung. The numbers of organisms in the lung increased rapidly, and by 30 h, a well-developed pneumonia was apparent. All the mice died within 4 days after infection. The therapeutic effectiveness of single-dose kanamycin regimens decreased markedly with a delay in administration. The effectiveness of multi-dose kanamycin regimens was influenced by the frequency of dosage. Thus a 12-h dosage schedule was superior to a 24-h regimen. Administration of 20 mg of kanamycin per kg at 12-h intervals for 10 days, initiated 30 h after infection, provided a complete cure. The infecting organisms in the lung, trachea, and blood were eradicated by the kanamycin therapy, but those in the nasal cavity were difficult to eliminate.
Effects of penicillin G on mesosome-like structures in Agmenellum quadruplicatum
Authors: Balkwill D L , Stevens S E
Published: June 2012

Agmenellum quadruplicatum was treated with lethal doses of penicillin G (15 and 75 U/ml) and then examined by electron microscopy to observe changes that took place before lysis. Treatment for 30 min led to increases in the frequency and size of mesosome-like structures within the cells. There was a direct correlation between the magnitude of these increases and the concentration of penicillin G. The mesosome-like structures often were associated with division septa, and they resembled mesosomes reported in other cyanobacteria. It is suggested that these structures appeared and enlarged because synthesis of membrane material continued after wall (peptidoglycan) synthesis was inhibited by the drug.
In vitro activities of cefotaxime and moxalactam (LY127935) against Haemophilus influenzae
Authors: Jorgensen J H , Crawford S A , Alexander G A
Published: June 2012

The in vitro activities of two new beta-lactam antibiotics, cefotaxime and moxalactam (LY127935), were compared with those of cefamandole, cefoxitin, cefuroxime, and ampicillin against both beta-lactamase-producing and non-beta-lactamase-producing isolates of Haemophilus influenzae. Both cefotaxime and LY127935 were highly active against all isolates irrespective of beta-lactamase production.
Metabolic regulation in tylosin-producing Streptomyces fradiae: regulatory role of adenylate nucleotide pool and enzymes involved in biosynthesis of tylonolide precursors
Authors: Vu-Trong K , Bhuwapathanapun S , Gray P P
Published: June 2012

The relationship was studied between the level of the intracellular adenylates and the biosynthesis of tylosin by Streptomyces fradiae NRRL 2702. The adenylate level was observed to be inversely related to the rate of tylosin biosynthesis and hence the final concentration of the antibiotic. The concentrations of the adenylates were maximal during the trophophase, dropped quickly before the onset of tylosin biosynthesis, and remained at low levels throughout the idiophase. The adenylate energy charge was almost constant throughout the fermentation and was in the range of 0.4 to 0.55. Glucose addition in the idiophase suppressed tylosin biosynthesis, accompanied by a rapid increase in the adenylate levels. The biosynthesis of tylosin resumed after a rapid drop in the adenosine triphosphate concentration. Two enzymes catalyzing the interconversion of propionyl-coenzyme A and methylmalonyl-coenzyme A were found in this organism: methylmalonyl-coenzyme A carboxyltransferase (EC 2.1.3.1) and propionyl-coenzyme A carboxylase (EC 6.4.1.3). The activity of the former was two orders of magnitude higher than that of the latter. The activities of both enzymes were affected by the increased glucose addition in the idiophase.
Boron-containing antibacterial agents: effects on growth and morphology of bacteria under various culture conditions
Authors: Bailey P J , Cousins G , Snow G A , White A J
Published: June 2012

The effects of a number of synthetic antibacterial agents of the borinic acid and diazaborine types on the growth of enteric bacteria were examined. In minimal medium aerobic growth was immediately slowed; slow nonexponential growth continued for an extended period, and the cells remained viable. The effect was also seen in anaerobic cultures and was not antagonized by a number of common nutrients, vitamins, or growth factors. The response was modified by the addition of casein hydrolysate to the medium. This seemed to be a nutritional effect dependent principally on lysine and leucine. The modified response consisted of a period of abnormal growth lasting for at least one doubling time after the addition of the antibacterial agent. The turbidity at first increased more rapidly than that of the controls and was approximately equal to that of the controls after 30 min. However, the increase in bacterial mass (dry weight) was only 0.75 of the amount predicted by the change in turbidity. The viable count increased in proportion to the turbidity. Changes in the cell envelope were revealed by electron microscopy and by an alteration in the response of cells to lytic agents. After the period of abnormal growth cultures entered a premature stationary phase.
Amantadine and ribavirin aerosol treatment of influenza A and B infection in mice
Authors: Wilson S Z , Knight V , Wyde P R , Drake S , Couch R B
Published: June 2012

Ribavirin, amantadine, and the two drugs in combination given in small-particle aerosol were highly effective in the treatment of influenza A infection in mice. Treatment was started 72, 96, and 120 h after inoculation and was given continuously for 4 days. With increasing delay in start of treatment, there was a pronounced reduction in effectiveness of ribavirin but not in that of amantadine. The combination treatment reflected the loss of ribavirin activity. Leukocyte infiltration and virus titers in the lungs were inversely related to the effectiveness of treatment. Influenza B infection treated 72 h after inoculation responded only to ribavirin, as indicated by the criteria described for influenza A. Intraperitoneal administration of drug begun 72 h after inoculation in regimens equivalent to aerosol afforded less protection than aerosol treatment.
Comparison of a radioimmunoassay and a microbiological assay for measurement of serum vancomycin concentrations
Authors: Crossley K B , Rotschafer J C , Chern M M , Mead K E , Zaske D E
Published: June 2012

A newly developed radioimmunoassay was used to measure the concentration of vancomycin in 137 specimens of serum from patients being treated with this antibiotic. Of these sera, 84 were also analyzed with a microbiological assay technique for vancomycin. Duplicate determinations were done with each of the techniques. Individual values and averaged values for both methods were used for statistical analyses. The correlation coefficients between all possible combinations of radioimmunoassay and microbiological assay results for the 84 sera were greater than or equal to 0.99 (P less than 0.01). Values for the regression coefficients of radioimmunoassay results on microbiological assay results ranged from 0.98 +/- 0.01 to 1.03 +/- 0.01. The mean percent deviation of radioimmunoassay versus microbiological assay results was -1.56 +/- 0.60. A one-way analysis of variance demonstrated that the use of different standard curves for each batch of specimens assayed by microbiological assay did not significantly influence the results (P = 0.07). The microbiological assay and the radioimmunoassay for measurement of serum vancomycin levels yielded essentially identical results.
Treatment of experimental staphylococcal infections: effect of rifampin alone and in combination on development of rifampin resistance
Authors: Mandell G L , Moorman D R
Published: June 2012

Rifampin is a potentially useful anti-staphylococcal agent, but resistance develops frequently when the drug is used alone. The efficacy of rifampin, trimethoprim, and a penicillin alone or in combination was examined in mice with acute or subacute infections. Mice were infected intraperitoneally with penicillin-susceptible Staphylococcus aureus. Survival after penicillin therapy was only 9.1% in contrast to survival after rifampin therapy which was 68% (P less than 0.001). No rifampin-resistant S. aureus were isolated from peritoneal fluid or heart blood samples from dead animals in these short-term experiments. Rifampin was ineffective (survival, 4.8%) for infections instituted with rifampin-resistant strains. Long-term experiments were conducted after intravenous injection of 4 x 10(8) S. aureus. Forty percent of the animals survived after methicillin therapy; 77% survived after rifampin therapy (P less than 0.001). However, 40% of those animals that died after rifampin therapy died with rifampin-resistant organisms. No animal dying in groups treated with a combination of rifampin and trimethoprim (85% survival) or rifampin and methicillin (79% survival) died with rifampin-resistant organisms. Thus, rifampin combined with a penicillin or trimethoprim was effective in preventing the development of rifampin-resistant strains.
Clinical and Pharmacokinetic Evaluation of Parenteral Cefoxitin in Infants and Children
Authors: Feldman William E. , Moffitt Steven , Sprow Nancy
Published: June 2012

Thirty-two infants and children ranging in age from 3 to 151 months (mean, 26 months) were treated with parenteral cefoxitin (150 mg/kg per day). Ten patients with isolates of
Haemophilus influenzae
(six with cellulitis, two with arthritis, and two with mastoiditis), four with
Staphylococcus aureus
(one with lymphadenitis, one with septicemia, and two with abscess), and three patients with
Streptococcus pneumoniae
(one each with cellulitis, abscess, and arthritis), were clinically and bacteriologically cured by therapy. Two additional patients with septic arthritis and facial cellulitis developed meningitis with
H. influenzae
type b and
S. pneumoniae
, respectively. Minimal inhibitory and bactericidal concentrations were ≤5 μg/ml for 15 isolates. Minimal bactericidal concentrations were >20 μg/ml for one strain of
S. aureus
and one of
H. influenzae
type b. The mean peak serum levels were 81.9 and 68.5 μg/ml 15 min after intravenous or intramuscular doses, respectively. The mean elimination half-lives were 42.4 and 40.1 min after intravenous or intramuscular doses, respectively. The mean volumes of distribution were 5,540 and 4,760 ml after intravenous and intramuscular doses, respectively. Mean plasma clearance was 242 and 257 ml/min per m
2
after intravenous and intramuscular doses, respectively. Therapy was discontinued in one patient because of neutropenia, which resolved after cefoxitin was stopped. Eosinophilia and transiently elevated liver function tests occurred in eight and six patients, respectively. These data indicate that cefoxitin may be an effective treatment for infections due to susceptible bacteria in the dosage tested, but its use may be limited because of the occurrence of meningitis during therapy in some patients.
Dissociation between the induction of potassium efflux and cytostatic activity of polyene macrolides in mammalian cells
Authors: Malewicz B , Jenkin H M , Borowski E
Published: June 2012

The paper contains data on the induction of K+ efflux and viability of baby hamster kidney (BHK-21) cells after their treatment with macrolide antibiotics inducing specific pores in membrane. New water-soluble semisynthetic derivatives of amphotericin B and aureofacin (N-glycosyl and trimethylammonium methyl ester derivatives) as well as the parent compounds were used to compare the concentration of antibiotics inducing permeabilizing and cytostatic effects. We found that a two- to eight-times-higher concentration of polyene antibiotic was required to observe a cytostatic effect than for release of 50% of the cellular potassium (K50 concentration) from BHK-21 cells. These differences were larger for water-soluble derivatives than for the parent compounds. The amount of intracellular potassium in treated cells incubated under optimal growth conditions was higher than in cells which had been further washed with K+-free maintenance medium. The membrane permeability changes induced by low concentrations of specific polyenes were observed to be reversible. BHK-21 cells were able to repair polyene-induced membrane permeability within 3 to 12 h under optimal growth conditions, after cell treatment with K50 concentration of specific macrolide antibiotics. The repair phenomenon is postulated as an explanation for the dissociation observed between permeabilizing and cytostatic effect of specific polyenes in BHK-21 cells.
Bioassay for determination of vancomycin in the presence of rifampin or aminoglycosides
Authors: Walker C N
Published: June 2012

Vancomycin determinations were performed in the presence of an aminoglycoside or rifampin. A previously reported bioassay method was modified by using a rifampin-resistant strain and increasing the NaCl concentration in the minimal salts-glucose assay agar from 0.2 to 6.0%.
Moxalactam (LY127935), a new semisynthetic 1-oxa-beta-lactam antibiotic with remarkable antimicrobial activity: in vitro comparison with cefamandole and tobramycin
Authors: Jones R N , Fuchs P C , Sommers H M , Gavan T L , Barry A L , Gerlach E H
Published: June 2012

Moxalactam (LY127935) exhibited greater in vitro activity than cefamandole and tobramycin against clinical isolates of Enterobacteriaceae, Aeromonas hydrophila, and Pseudomonas maltophilia. The activities of the three drugs against other microorganisms were as follows: for staphylococci, cefamandole = tobramycin greater than moxalactam; for streptococci, cefamandole greater than moxalactam greater than tobramycin; and for Pseudomonas aeruginosa, tobramycin greater than moxalactam greater than cefamandole. Moxalactam also demonstrated significant activity against the Bacteroides fragilis group and other anaerobes. Moxalactam was comparable to cefotaxime (HR756) in its inhibition of cephalothin-resistant and aminoglycoside-resistant clinical isolates.
Antibiotic resistance in Neisseria denitrificans
Authors: MacKenzie C R , McDonald I J , Johnson K G
Published: June 2012

An ampicillin-resistant strain of Neisseria denitrificans was produced by serial passage of the organisms in media containing increased concentrations of antibiotic. The 400-fold increase in resistance obtained was a relatively stable characteristic. Ampicillin resistance in this organism was apparently related to a loss or modification of the penicillin-binding proteins associated with the cytoplasmic membranes. Membranes isolated from the ampicillin-resistant strain bound significantly less radioactive penicillin than those isolated from the parent strain and revealed one major and three minor penicillin-binding proteins. All four penicillin-binding proteins were present in reduced amounts or had a decreased capacity for penicillin binding in the ampicillin-resistant cells. The increased resistance did not involve enzymic degradation of the antibiotic or a general reduction in the permeability of the outer layers of the cell. No difference in the amount of peptidoglycan present in the parent and ampicillin-resistant cells or in the gross chemical structure of the peptidoglycans of the two strains was observed.
Biliary excretion of cephalosporins in rats: influence of molecular weight
Authors: Wright W E , Line V D
Published: June 2012

The biliary excretion of 18 cephalosporin derivatives with varying 3- and 7-substituents was examined in cannulated rats. In spite of the widely differing physical chemical properties imparted by the different structures, the dominant influence on the degree of biliary excretion was the molecular weight of the compound. Above a threshold molecular weight of about 450, biliary excretion increased in a generally progressive way, becoming the principal route of excretion of the higher-molecular-weight derivatives. Examples were found in which the molecular weight influence was modified but not abolished by specific substituents. Biliary excretion varied from less than 5% to greater than 90% of the dose. Interruption of bile flow resulted in an increase in urinary excretion. Biliary excretion may influence the evaluation of new cephalosporins in rodent models. Such influence must be considered when selecting candidate compounds intended for eventual use in humans, where the excretion pattern may be different from that in rodents.
In vitro activities of miconazole, miconazole nitrate, and ketoconazole alone and combined with rifampin against Candida spp. and Torulopsis glabrata recovered from cancer patients
Authors: Moody M R , Young V M , Morris M J , Schimpff S C
Published: June 2012

A total of 440 fresh clinical isolates of yeasts from cancer patients were tested by an agar dilution technique against miconazole, miconazole nitrate, and ketoconazole individually and combined with 5 micrograms of rifampin per ml. Most strains of Candida albicans were susceptible to 0.5 microgram or less of the imidazoles per ml. Candida tropicalis required 2 to 4 micrograms of miconazole and its nitrate base per ml for inhibition and was resistant to ketoconazole. The 100% minimal inhibitory concentration of the imidazoles for Candida krusei was 1 microgram/ml. Susceptibility to 4 micrograms of miconazole and miconazole nitrate per ml occurred in 73 and 87% of Torulopsis glabrata strains, respectively, and none was susceptible to ketoconazole. Miconazole was most effective against the Candida spp., whereas its nitrate base was most active against T. glabrata. Synergy was observed when rifampin was combined with miconazole and miconazole nitrate but was not observed when rifampin was combined with ketoconazole. Synergy occurred most frequently when rifampin was combined with miconazole nitrate.
Antiviral activity of tunicamycin on herpes simplex virus
Authors: Katz E , Margalith E , Duksin D
Published: June 2012

Tunicamycin (0.5 microgram/ml) significantly lowers (2 to 3 log10) the infectious yield of herpes simplex virus type 1 grown in chicken embryo fibroblasts and in BSC1 cells. Although virus particles are formed and the synthesis of the viral deoxyribonucleic acid is only partially affected by the antibiotic, the glycosylation of herpesvirus glycopeptides is amost completely inhibited. The morphology of virus particles made in the presence of tunicamycin is similar to that of intact virus particles, as demonstrated by electron microscopy. This suggests that the absence of the carbohydrate side-chain from the viral glycopeptides does not affect the overall integrity of the virion but decreases very significantly the infectivity of these particles.
Factors affecting gentamicin assay
Authors: Nilsson L
Published: June 2012

Measurements of gentamicin concentrations in serum by the luciferase method are affected by sodium phosphate, glucose, and heparin. The effects of the first two factors can be eliminated by omitting phosphate and increasing the level of glucose in the culture medium. The effects of heparin cannot be easily circumvented, thus precluding use of this agent as an anticoagulant. Bilirubin, which purportedly inhibits measurement of gentamicin in serum by the disk diffusion assay, does not affect the accuracy of the luciferase method.
Sulfamethoxazole- trimethoprim versus ampicillin in treatment of acute invasive diarrhea in adults
Authors: Barada F A , Guerrant R L
Published: June 2012

Twenty-seven Navajo adults with moderate to severe acute inflammatory diarrhea were hospitalized and randomly given ampicillin or sulfamethoxazole-trimethoprim. All patients had invasive diarrhea as defined by sheets of fecal leukocytes, seen on methylene blue wet-slide preparations, and significant clinical symptoms, including postural hypotension from dehydration or fever (temperature greater than 100 degrees F [or 37.8 degrees C]). Patients were followed daily for 5 days in the hospital. Responses of symptoms in all 13 patients who were given sulfamethoxazole-trimethoprim were comparable to or better than those 14 patients randomly assigned to receive ampicillin. Nineteen (73%) of the 27 patients had culture-proven shigellosis, 6 of whom had ampicillin-resistant Shigella isolates. All isolates were susceptible to sulfamethoxazole-trimethoprim in vitro. The eight patients with culture-proven shigellosis treated with sulfamethoxazole-trimethoprim responded as well as the eight patients with ampicillin-susceptible infections treated with ampicillin. Three of the eight patients successfully treated with sulfamethoxazole-trimethoprim had ampicillin-resistant organisms. The three patients with ampicillin-resistant organisms who were treated with ampicillin appeared to do less well; one was a clinical and bacteriological failure at 72 h and subsequently improved after sulfamethoxazole-trimethoprim therapy. As predicted by in vitro susceptibility studies and by studies in children, sulfamethoxazole-trimethoprim was highly effective in treating adult patients with shigellosis and appears to be the treatment of choice in areas where ampicillin resistance among Shigella is common.