bluuebunny/crossref_metadata_2025 huggingface dataset:
Side Effects of Minocycline: A Double-Blind Study
Authors: Fanning W. Lee , Gump Dieter W. , Sofferman Robert A.
Published: June 2012

We studied the incidence and type of side effects of minocycline in a double-blind study. A total of 45 volunteers (18 men and 27 women) were given minocycline, and 44 volunteers (23 men and 21 women) were given placebo. The men in both the minocycline and placebo groups were significantly (
P
< 0.0001) larger than the women in the comparable groups. Minocycline dosage was 100 mg every 12 h for 5 days, and placebo was administered in an identical manner. Minocycline serum concentrations were determined in 12 volunteers at 1, 2, 4, and 6 h after the morning doses on days 1, 3, and 5 of the study. Side effects were recorded by volunteers in diaries and also through daily interviews and were evaluated by examination and electronystagmography. Peak minocycline serum concentrations were seen by day 3 and correlated with the peak onset of side effects. These concentrations were significantly higher in women than in men. Vestibular side effects occurred in 70.4% of the women on minocycline and significantly (
P
< 0.0001) exceeded the rate of the women on placebo (9.5%). Only loss of balance was significantly (
P
< 0.05) increased in the men taking minocycline as contrasted with men on placebo. Electronystagmography generally revealed no abnormalities. Side effects were usually not severe: four volunteers in the minocycline group and two in the placebo group discontinued their capsules because of side effects. It is concluded that women experience an unacceptably high incidence of side effects from minocycline, and this may be related to their higher serum concentrations, which in turn may relate to their smaller size.
Effects of Ionenes on Interferon Induction by Poly(Inosinic Acid)·Poly(Cytidylic Acid)
Authors: De Clercq Erik , Janik Borek , Sommer Ronald G.
Published: June 2012

Depending on the spacing of their positive charges, ionenes, a class of quaternary ammonium polymers, increased the interferon-inducing activity of poly(inosinic acid)·poly(cytidylic acid) in mouse L-929 cells, whereas they did not enhance poly(inosinic acid)·poly(cytidylic acid) induced interferon production in primary rabbit kidney and human skin fibrolast cells.
Amoxicillin Therapy of Acute Urinary Infections in Adults
Authors: Ronald A. R. , Jagdis F. A. , Harding G. K. M. , Hoban S. A. , Muir P. L. , Gurwith M. J.
Published: June 2012

Fifty-two patients, 48 females and 4 males, with suspected urinary infection were treated with amoxicillin. Twenty-two females with presumed bladder infection were treated with amoxicillin, 250 mg three times a day for 7 days; 26 females and 4 males with presumed renal infection were treated with amoxicillin, 500 mg three times a day for 14 days. Five patients were immediate treatment failures, with positive urine cultures during therapy. All five patients had been infected with amoxicillin-resistant urinary pathogens. Three patients, treated as for bladder infections, reinfected during 6 weeks of follow-up, and only one relapsed. Two patients, treated as for renal infections, reinfected, whereas four relapsed. During therapy, amoxicillin-susceptible gram-negative rods were eradicated from the periurethral area in all but one patient. Of 28 patients studied, 19 acquired a predominant growth of either resistant aerobic gram-negative rods or
Candida albicans
from periurethral cultures. Our findings suggest that these two regimens of amoxicillin achieve satisfactory cure rates in urinary infection, but both regimens significantly alter the normal periurethral flora.
In Vitro Activity of Netilmicin Compared with Gentamicin, Tobramycin, Amikacin, and Kanamycin
Authors: Eickhoff Theodore C. , Ehret Josephine M.
Published: June 2012

The in vitro activity of netilmicin was compared with that of gentamicin, tobramycin, amikacin, and kanamycin against 636 strains of bacteria recently isolated from clinical sources. Gentamicin was the most active antibiotic, but netilmicin and tobramycin closely paralleled it. Netilmicin was generally four-to eightfold less active than gentamicin against
Serratia
and group A streptococci, and was twofold less active against
Pseudomonas aeruginosa
. When effects of inoculum size and concentration of divalent cations in the media were evaluated, netilmicin was shown to be similar to gentamicin in vitro. Minimum inhibitory concentrations for
P. aeruginosa
were increased as much as 18-fold when the Mg
2+
and Ca
2+
concentrations were increased to physiological levels in Mueller-Hinton broth.
Effect of Probenecid on the Blood Levels and Urinary Excretion of Cefamandole
Authors: Griffith R. S. , Black H. R. , Brier G. L. , Wolny J. D.
Published: June 2012

Two oral 0.5-g doses of probenecid given 7 and 1 h before a single 1-g intramuscular dose of cefamandole resulted in higher serum levels of cefamandole than when cefamandole was given alone: 37 versus 20 μg per ml of serum, respectively. Cefamandole was not measurable (<0.3 μg/ml) at 8 h when it was given alone, whereas an average 8-h value of 2.9 μg/ml was obtained after pretreatment with probenecid. By prolonging the duration of these high cefamandole levels, probenecid should permit the treatment of more serious clinical infections, including those due to relatively resistant organisms, or permit a reduction in either the dosage of cefamandole or the frequency of administration.
Activities of Various 4-Aminoquinolines Against Infections with Chloroquine-Resistant Strains of
Plasmodium falciparum
Authors: Schmidt L. H. , Vaughan Dennis , Mueller Donna , Crosby Ruth , Hamilton Rebecca
Published: June 2012

The studies reported here stemmed from a personal report by Geiman on the capacity of the 4-aminoquinoline amodiaquin to inhibit in vitro maturation of ring stages of the chloroquine-resistant Monterey strain of
Plasmodium falciparum
. This observation, confirmed in owl monkeys infected with this strain, led to a comparison of the activities of chloroquine, amodiaquin, amopyroquin, and dichlorquinazine (12,278 RP) against infections with various chloroquine-susceptible and chloroquine-resistant strains. The results showed that: (i) these 4-aminoquinolines were essentially equally active against infections with chloroquine-susceptible strains and (ii) the activities of amodiaquin, amopyroquin, and dichlorquinazine were reduced significantly in the face of chloroquine resistance, but (iii) well-tolerated doses of these compounds would cure infections with strains that fully resisted treatment with maximally tolerated doses of chloroquine. Two other 4-aminoquinolines, SN-8137 and SN-9584, which also exhibited activity against chloroquine-resistant parasites in vitro, displayed curative activity in monkeys infected with a chloroquine-resistant strain. These observations show that there is cross-resistance among the 4-aminoquinolines, confirming earlier findings, but indicate that the dimensions of this phenomenon are sufficiently limited so that some derivatives are therapeutically effective against infections refractory to maximally tolerated doses of chloroquine.
Azlocillin: In Vitro Studies of a New Semisynthetic Penicillin
Authors: Stewart Dorothy , Bodey Gerald P.
Published: June 2012

The activity of azlocillin, a new semisynthetic penicillin, was determined against 582 clinical isolates of gram-negative bacilli and gram-positive cocci. Over 75% of the isolates of
Pseudomonas aeruginosa
were inhibited at a concentration of 12.5 μg or less per ml. Azlocillin is also active against indole-negative and -positive
Proteus
spp., inhibiting 98 and 71%, respectively, at a concentration of 12.5 μg or less per ml. Isolates of
Klebsiella
spp. and
Enterobacter
spp. showed less susceptibility than isolates of
Escherichia coli
and
Serratia
spp. Gram-positive cocci except penicillin G-resistant
Staphylococcus aureus
were susceptible to azlocillin. Azlocillin failed to inhibit the growth of gram-negative bacilli when large inocula were used. It was more active in alkaline pH, but the type of medium used had little effect on its activity. Azlocillin was more active than mezlocillin, ticarcillin, and carbenicillin and as active as BLP-1654 against isolates of
P. aeruginosa
. It was not as active as mezlocillin against the majority of the other gram-negative bacilli.
Energy Coupling Factor as Target of Colicin K: Characterization of a Colicin K-Insensitive
ecf
Mutant of
Escherichia coli
Authors: Hong Jen-Shiang , Haggerty D. Lynne , Lieberman Michael A.
Published: June 2012

We isolated a colicin K-insensitive energy uncoupled mutant of
Escherichia coli
. This mutant was presumed to be an
ecf
mutant as evidenced by its similarity to a known
ecf
mutant (M. A. Lieberman and J.-S. Hong, 1974) with respect to the mutational site, reversion pattern, and defects in transport and growth. The mutation conferring the colicin K-insensitivity resided in the
ecf
gene as the majority of the secondary mutations overcoming the
ecf
phenotype reverted the colicin K-insensitive phenotype to colicin K-sensitive. The insensitivity of the mutant to colicin K was not due to either a defect in adsorption or to a lack of the energized membrane state. The defect was most probably due to the inability of colicin K molecules to interact with their target. Our previous studies concerning the role of the
ecf
gene product in energy coupling to active transport and oxidative phosphorylation support the contention that the ECF protein is itself the direct target of colicin K.
Susceptibility of Anaerobic Bacteria to Cefoxitin and Related Compounds
Authors: Bach Vinth Toan , Roy Ira , Thadepalli Haragopal
Published: June 2012

Cephalothin, cefazolin, cephradine, and cefoxitin inhibited more than 75% of 326 anaerobic bacteria in vitro, but cefoxitin was the most effective against anaerobes in general and
Bacteroides fragilis
in particular.
Exudate Levels and Bactericidal Activity of Cefazolin in a New Local Infection System Using Rat Granuloma Pouches
Authors: Nishida Minoru , Murakawa Takeo
Published: June 2012

An experimental local infection system has been developed in which exudates are induced with croton oil in granuloma pouches of rats. This system provided a suitable model for the evaluation of the therapeutic effect of two antibiotics, cefazolin and cephalothin. Exudate levels of cefazolin were found to be higher than those of cephalothin, and these levels correlated with the higher serum level of cefazolin. The therapeutic effect of cefazolin, after intramuscular injection of 20 mg of each antibiotic per kg, was superior to that of cephalothin in eradicating both
Staphylococcus aureus
and
Escherichia coli
.
Five-Hour Minimal Inhibitory Concentration Test of Four Antimicrobial Agents for
Pseudomonas aeruginosa
Authors: Brown W. J. , Sautter R. L.
Published: June 2012

A rapid 5-h minimal inhibitory concentration procedure and a minimal bactericidal concentration procedure are described for testing
Pseudomonas aeruginosa
against gentamicin, tobramycin, amikacin, and carbenicillin. The rapid test results were demonstrated to correlate with the conventional tube dilution procedure.
Effect of Anaerobiosis on Antimicrobial Susceptibility of Staphylococci
Authors: Harrell Lizzie J. , Evans James B.
Published: June 2012

The minimum inhibitory concentration (MIC) of 12 antibiotics was determined for four strains of staphylococci (representing the three major species) under aerobic and anaerobic conditions by using the broth dilution method. Nine of the antibiotics showed no significant difference between aerobic and anaerobic MIC for any of the four cultures. Gentamicin and kanamycin showed a small, but significant, increase in MIC for at least two strains under anaerobic conditions. Trimethoprim was less effective against all strains under anaerobic conditions.
Incidence and Elimination of R Plasmids in
Vibrio cholerae
Authors: Dastidar Sujata G. , Poddar Roma , Kumar Ranajit , Chakrabarty A. N.
Published: June 2012

Of 124 strains of
Vibrio cholerae
, 32 were multiply resistant to antibiotics. This resistance appeared to be determined by R plasmids on the basis of their effective elimination by sodium dodecyl sulfate, acridine orange, ethidium bromide, and ultraviolet radiation.
Inhibition of Amino Acid Transport in
Escherichia coli
by Some Beta-Lactam Antibiotics
Authors: Anderson Scott V. , Berg Claire M.
Published: June 2012

Among 10 antibiotics tested, cephaloridine and cephalothin showed the greatest inhibition of proline active transport. Ethylenediaminetetraacetate pretreatment of the cells did not enhance inhibition by any of these 10 antibiotics. The inhibition of active transport of 10 additional amino acids by cephaloridine and cephalothin was studied. Both antibiotics inhibited transport of three amino acids which, like proline, have transport systems resistant to osmotic shock; neither antibiotic inhibited transport of the remaining amino acids, including three with shock-resistant and four with shock-sensitive systems.
Activity of Spectinomycin Against Anaerobes
Authors: Rosenblatt Jon E. , Gerdts Alice M.
Published: June 2012

The in vitro inhibitory activity of spectinomycin was tested against various anaerobic bacteria. Different results were obtained with different media and with different initial pH's of the media. The highest minimum inhibitory concentrations for
Bacteroides fragilis
([Formula: see text] 128 μg/ml) were obtained with the use of Wilkins-Chalgren agar (pH 7.2) and Brucella blood agar (pH 7.0). Brucella blood agar at higher pH's (7.4 and 8.0) and Mueller-Hinton and Diagnostic Sensitivity Test agars produced lower minimum inhibitory concentrations (32 and 64 μg/ml). This same relationship between spectinomycin activity and pH of the medium was, in general, observed with these media and other anaerobes, including isolates of
B. melaninogenicus, Fusobacterium
, gram-positive cocci,
Clostridium perfringens
, and
C. ramosum
. The variable results observed in this study and in two others make it difficult to predict the clinical usefulness of spectinomycin in the treatment of anaerobic infections. It is probably most appropriate to be guided by results obtained with Wilkins-Chalgren agar and the method proposed as a reference to the National Committee for Clinical Laboratory Standards. These results indicate that spectinomycin is not a potent inhibitor of
B. fragilis
or other clinically significant anaerobes.
Comparison of Pharmacological and Antimicrobial Properties of Cefadroxil and Cephalexin
Authors: Hartstein A. I. , Patrick K. E. , Jones S. R. , Miller M. J. , Bryant R. E.
Published: June 2012

Pharmacological and antimicrobial properties of cefadroxil, a new cephalosporin antibiotic, were compared with cephalexin. Absorption and excretion were studied in 20 healthy men. Peak concentrations of the drugs in serum were similar after ingestion of single 500-mg tablets. The concentration of cefadroxil in serum was more sustained than that of cephalexin. Levels of cefadroxil in serum after a dose of 1,000 mg were approximately twice those after a 500-mg dose through 6 h. Each drug administered in a dose of 500 mg every 6 h for 24 h resulted in concentrations in serum that were similar to a single dose without accumulation. Ninety-three percent of the cefadroxil and 85% of the cephalexin were excreted in urine after ingestions of single 500-mg tablets. The urine concentration of cefadroxil was more sustained than cephalexin. Minimal inhibitory and minimal bactericidal concentrations for clinical isolates were comparable with each drug. Cefadroxil compares favorably with cephalexin in this study. Sustained levels of cefadroxil in serum and urine suggest that this drug may be given at less frequent intervals than cephalexin.
Comparative Pharmacology of Cefaclor and Cephalexin
Authors: Korzeniowski Oksana M. , Scheld W. Michael , Sande Merle A.
Published: June 2012

Two cephalosporin antibiotics, cefaclor and cephalexin, were administered orally to healthy, adult male volunteers for comparison of their pharmacological properties. In doses of 250 mg orally, cefaclor produced a peak serum concentration of 6.01 ± 0.55 (standard deviation [SD]) μg/ml compared with 9.43 ± 2.36 μg/ml for cephalexin (
P
< 0.01). The half-lives were 0.58 ± 0.07 (SD) h and 0.80 ± 0.12 (SD) h, and elimination constants were 1.22 ± 0.15 and 0.88 ± 0.13 h
−1
for cefaclor and cephalexin, respectively (
P
< 0.001). Neither drug showed accumulation over the dosing period, and both were well tolerated.
Synergy of Penicillin-Netilmicin Combinations Against Enterococci Including Strains Highly Resistant to Streptomycin or Kanamycin
Authors: Sanders Christine C.
Published: June 2012

The in vitro activity of combinations of penicillin and netilimicin was determined against 20 clinical isolates of enterococci and compared with that obtained in simultaneous tests with penicillin/sisomicin, penicillin/streptomycin, and penicillin/kanamycin. Synergy between the two drugs in each combination was determined by the use of quantitative kill curves and was defined as a killing by the combination at least 100-fold greater than that produced by the most effective drug alone. Penicillin/netilmicin and penicillin/sisomicin combinations were found to be synergistic against the majority of isolates tested, including strains resistant to penicillin/streptomycin or penicillin/kanamycin combinations. This synergy with penicillin could be demonstrated at a concentration of ≤7 μg/ml for either netilmicin or sisomicin. Studies on the kinetics of killing produced by these combinations showed the rate and extent of killing to be directly dependent upon the organism's relative susceptibility to the aminoglycoside alone and the aminoglycoside concentration in the combination. Results also indicated that the interaction between penicillin and netilmicin was true synergy; i.e., rapid and complete killing was produced by combinations containing each drug at concentrations insufficient to produce any killing alone, and the killing observed could not be produced by either drug alone at a concentration equivalent to the total drug concentration in the combination. The potential clinical application of this synergistic interaction should be investigated further, especially in view of recent reports showing netilmicin to be considerably less toxic than gentamicin in experimental animals.
Anti-
Candida
Activity of Clotrimazole in Combination with Dioctyl Sodium Sulfosuccinate and Other Surfactants
Authors: Iwata Kazuo , Yamaguchi Hideyo
Published: June 2012

Six anionic and five nonionic surfactants were tested for their effect on the fungistatic action of clotrimazole against
Candida albicans
. All of the anionic agents that did not contain an ethylene oxide group were capable of potentiating the anti-
Candida
activity of clotrimazole, whereas all five members of the polyoxyethylene surfactant group, including four nonionic agents and one anionic agent, acted in an antagonistic fashion. The combination of clotrimazole and the anionic surfactant dioctyl sodium sulfosuccinate was the most potent in synergy and, thus, more precise studies were made with this combination. Although appropriate combinations of the two drugs showed a potent fungicidal activity against proliferating cultures, none of these combinations tested was lethal when cell growth was restricted by nutritional deficiency. The lethal effect of the combined drugs was partly reversed when growing cultures were treated in the presence of an osmotic stabilizer. Whether cells were treated with moderate and higher concentrations of clotrimazole and dioctyl sodium sulfosuccinate, alone or in combination, there was little change in cell wall content of total protein, carbohydrate, or lipid from that in untreated control cells. However, there was a significant decrease in the cell wall content of phospholipid when moderate concentrations of the two drugs were combined.
Maternal-Fetal Pharmacology of Cefatrizine in the First 20 Weeks of Pregnancy
Authors: Bernard Betty , Thielen Paul , Garcia-Cázares Salvador J. , Ballard Charles A.
Published: June 2012

To evaluate maternal-fetal pharmacology of cefatrizine (BL-S 640), a new oral cephalosporin, a single oral 1,000-mg dose was administered to 33 gravidas (8 to 20 weeks' gestation) at varying intervals within 46 h of an elective therapeutic abortion by hysterectomy or intra-amniotic prostaglandin F
2a
induction. Mean maternal serum concentrations at 1, 2, 4, and 8 h were 3.7, 7.9, 6.5, and 1.6 μg/ml; beyond a 3-h peak, a half-life of 2.4 h was determined. Cefatrizine placental half-life was 4.4 h. None of the 11 fetuses from a prostaglandin F
2a
abortion revealed cefatrizine activity; in contrast, 17 of 22 fetuses from a surgical abortion demonstrated cefatrizine concentrations in two or more samples. Fetal cefatrizine levels were less than 3 μg/g or μg/ml in kidney and urine, less than 2 μg/ml in serum and bile, and less than 2.5 μg/g in lung. After a single maternal dose, cefatrizine has a wide distribution in the fetus in the first half of gestation.
Function of the Outer Membrane of
Escherichia coli
as a Permeability Barrier to Beta-Lactam Antibiotics
Authors: Zimmermann Willy , Rosselet Armel
Published: June 2012

On the basis of a simple theoretical model, the ease of penetration of β-lactam antibiotics through the outer membrane of
Escherichia coli
was measured. The cell envelope was found to act as a diffusion barrier to both penicillins and cephalosporins. The validity of the model and the cooperative action of cell-bound β-lactamase and outer membrane were further verified by comparing calculated and experimentally determined velocities of β-lactam hydrolysis by intact cells and sonically treated cell suspensions. The results showed good correspondence at five different antibiotic concentrations. Similar conclusions could be drawn from a comparison of β-lactam concentrations on both sides of the outer membrane, calculated from enzyme kinetic measurements and minimal inhibitory concentrations for both a β-lactamase-producing
E. coli
and its enzyme-negative variant. in the case of benzylpenicillin and cephalothin, however, no correspondence was found. The joint action of several parameters determining the efficacy of penicillins and cephalosporins against β-lactamase-producing
E. coli
is discussed.
Comparative Study of Trichothecin, Amphotericin B, and 5-Fluorocytosine Against
Cryptococcus neoformans
In Vitro and In Vivo
Authors: Sneller M. R. , Hariri A. , Sorenson W. G. , Larsh H. W.
Published: June 2012

Trichothecin (T-cin), amphotericin B (AB), and 5-fluorocytosine (FC) were compared singly and in combination for capacities to inhibit growth of
Cryptococcus neoformans
in culture and to protect mice bearing infections with this yeast. The minimum inhibitory concentrations for T-cin, AB, and FC were found to be 0.5, 0.2, and 5.0 μg/ml, respectively. In vitro viability studies demonstrated a marked reduction in colony counts with the AB-FC combination and additive effects with the AB–T-cin and FC–T-cin combinations for a 3-day period. In mice infected intravenously with
C. neoformans
, the mean effective dose for AB was 0.38 mg/kg, and for FC it was 100 mg/kg for a 30-day treatment period. No mean effective dose could be ascertained when T-cin was tested at doses of 0.1 to 50 mg/kg. Despite this, marked beneficial effects were noted in vivo with the AB–T-cin combination, whereas additive effects and indifference were observed for AB-FC and FC–T-cin combinations, respectively. High-dose T-cin controls survived despite having received a cumulative dosage of more than twice the reported (LD
50
) mean lethal dose value.
Effect of Cefamandole Nafate on the Toxicity of Tobramycin
Authors: Wold J. S. , Turnipseed S. A. , Broddle W. D. , Owen N. V.
Published: June 2012

Because of the potential for an interaction between cephalosporins and aminoglycosides leading to renal injury, an evaluation of the effect of a new cephalosporin, cefamandole nafate, on the toxicity of the aminoglycoside tobramycin was performed in laboratory animals. High doses of cefamandole nafate did not increase the acute toxicity (lethality) of tobramycin in rats or mice. In a subacute experiment in rats, dose-related tobramycin nephrotoxicity, as evidenced by blood urea nitrogen changes, increased kidney weights, and histologically determined tubular nephrosis and necrosis, was observed. Concomitant treatment with cefamandole nafate, 500 mg/kg, did not increase tobramycin nephrotoxicity, but protected against the aminoglycoside-induced renal injury. Determination of tissue radioactivity after administration of [
14
C]tobramycin indicated that cefamandole nafate treatment resulted in uniformly lower tobramycin tissue concentrations compared with the control, suggesting that the protective effect was produced by enhanced excretion of tobramycin after cefamandole nafate treatment.
Antibiotic Concentrations in Serum, Serum Bactericidal Activity, and Results of Therapy of Streptococcal Endocarditis in Rabbits
Authors: Carrizosa Jaime , Kaye Donald
Published: June 2012

The correlation between antibiotic concentrations in serum, serum bactericidal activity, and results of therapy was studied in rabbits with streptococcal endocarditis. Five days of procaine penicillin G reduced bacterial titers to <10 per g in 12 of 14 vegetations in rabbits receiving 75,000 U intramuscularly every 6 h and 10 of 20 in rabbits given 37,500 U. Ten days of 18,750 U every 6 h did not reduce the titers. To test for cure, rabbits were treated with 75,000 U every 6 h for 10 or 20 days and then received no therapy for 7 days. At the end of the 7-day period without therapy, vegetations were sterile in five of five and eight of eight animals, respectively. Rabbits received 37,500 U every 6 h for 5, 10, or 20 days and then no therapy for 7 days, after which vegetations were sterile in one of seven, four of nine, and seven of eight animals, respectively. The median maximal serum bactericidal dilutions at 1 h were 1/16 when 75,000 U of procaine penicillin G was administered, 1/8 to 1/16 with 37,500 U, and 1/4 to 1/8 with 18,750 U. Serum bactericidal activity could not be detected in 50% of the rabbits 6 h after administration of 37,500 U. Cure was related to a median maximal serum bactericidal dilution of at least 1/8 to 1/16 1 h after penicillin administration. A median maximal serum bactericidal dilution of 1/4 to 1/8 resulted in unsuccessful therapy.
Cyclic Thymineless Death Significantly Increases Frequency of R-Plasmid Elimination
Authors: Tribe M. J. , Pinney R. J.
Published: June 2012

Thymine starvation of
Escherichia coli
strain C600
thy
(R46) eliminated the R plasmid at a frequency of 17%. This was increased fourfold, to 68%, after the same culture was subjected to an additional three cycles of growth followed by thymineless death.
Rapid Microdilution-Colorimetric Assay for Yeast Susceptibility to Fluorocytosine
Authors: Fisher Bruce D. , Armstrong Donald
Published: June 2012

Acid production by certain yeast species through the fermentation of glucose was used as the basis of an in vitro test for measuring susceptibility of these organisms to 5-fluorocytosine. Serial dilutions of 5-fluorocytosine in yeast nitrogen base broth, with bromothymol blue indicator dye, were made on microtiter plates. A fixed-concentration suspension of yeast cells was added to successive wells of the plates, and the color change from blue to yellow, indicating generation of acid, was noted. Eighteen hours after inoculation the lowest concentration of 5-fluorocytosine that completely inhibited the production of acid was recorded as the minimum inhibitory concentration. The results were reproducible in multiple trials with organisms of the genera
Candida, Torulopsis
, and
Saccharomyces
. This test is a rapid, inexpensive alternative to current 48- to 72-h methods in which broth turbidity is used as the end point.
Amikacin and Cephalothin: Empiric Regimen for Granulocytopenic Cancer Patients
Authors: Hahn Davis M. , Schimpff Stephen C, , Young Viola Mae , Fortner Clarence L. , Standiford Harold C. , Wiernik Peter H.
Published: June 2012

Amikacin (15 mg/kg per day) was used in combination with cephalothin (7 g/m
2
per day) as an empiric regimen for de novo febrile (>101°F [38.3°C]) episodes in 93 granulocytopenic (<1,000/mm
3
) cancer patients. Both drugs were given intravenously in four equal doses every 6 h. The response rate for all documented infections was 83%, including 11 of 17 (65%) bacteremias.
Escherichia coli
(14 cases) was the most common pathogen, whereas
Pseudomonas aeruginosa
(2 cases) caused fewer infections. Mean amikacin serum levels were 8.7 μg/ml at 1 h and 2.2 μg/ml at 5 h. Failure of bone marrow recovery in association with a bacteremia was a bad prognostic sign (only two of eight improving). Ototoxicity occurred in two (2%) patients, whereas presumed antibiotic-induced nephrotoxicity developed in six (7%) patients. Surveillance cultures (nose, gums axilla, and rectum) of all hospitalized patients revealed no significant change in the incidence of amikacin resistance. The combination of amikacin and cephalothin in this dose and schedule was safe and efficacious in these granulocytopenic patients.
Lack of Effect of Methenamine in Suppression of, or Prophylaxis Against, Chronic Urinary Infection
Authors: Vainrub Bernardo , Musher Daniel M.
Published: June 2012

Methenamine is frequently prescribed for patients who have chronic urinary infection to suppress bacterial growth during active infection or to prevent recurrence once an infection has been brought under control. We have examined the effect of methenamine mandelate and ascorbic acid on bacteriuria in para- and quadriplegics from a spinal cord unit. Patients with indwelling urinary catheters and those on a program of intermittent catheterization were included. No suppressive or prophylactic effect of this regimen was observed in any of our patients. Methenamine does not appear to be an effective antimicrobial agent in subjects who have an indwelling urinary catheter or in patients with spinal cord injury who are on intermittent catheterization. Since there appears to be reason to question the efficacy of methenamine in situations in which it is usually prescribed, evidence should be sought for a therapeutic effect in other cases. If no benefit is observed, the drug should not be used.
Quantitative Inhibition of
Haemophilus influenzae
by Trimethoprim/Sulfamethoxazole
Authors: Pelton Stephen I. , Shurin Paul A. , Klein Jerome O. , Finland Maxwell
Published: June 2012

We evaluated the inhibitory effect of trimethoprim (TMP) and sulfamethoxazole (SMZ), alone and in combination, against 34 strains of
Haemophilus influenzae
. Growth inhibition was determined after incubation for 18 h by comparing viable counts of cultures in drug-containing medium with corresponding counts of control cultures in drug-free medium. In a modified, thymidine-deficient Levinthal broth, the numbers of colony-forming units of all the isolates tested were reduced 100-fold or more by TMP/SMZ (1.25/25 μg/ml) as compared with growth without drug. Inhibition was significantly greater with TMP/SMZ than with either TMP or SMZ alone. Ampicillin-susceptible and ampicillin-resistant strains were equally susceptible to TMP/SMZ. Growth of nontypable strains was inhibited more than growth of type b organisms.
Use of a Photodensitometric Technique to Quantify Microscopic Lung Lesions in Mice: Antiviral Activity Against Swine Influenza Virus
Authors: Hall William C. , White John D. , Scott George H.
Published: June 2012

During studies of swine influenza virus (A/NJ/76) infection, a technique was devised to quantify the pulmonary lesions in infected mice treated at different time intervals with antiviral chemotherapeutic agents. The technique is based on the premise that as the severity of microscopic change increases, the optical density of lung sections also increases because of edema and increased cell numbers in infected lungs. Seven days after intranasal instillation of the virus, mice were killed and the lungs were perfused with 2% glutaraldehyde at constant pressure. Lungs were processed in a routine manner, sectioned at standard levels, and stained with hematoxylin and eosin. By using standard photomicrography equipment, multiple optical density measurements were made of lung sections in a carefully controlled systematic manner, and a mean optical density was determined for each lung. The optical density of lungs of mice treated before and after infection with amantadine, rimantadine, or ribavirin was significantly reduced compared with that of the lungs of infected, untreated controls. If treatment was delayed until 15 h after infection, amantadine and ribavirin were effective in reducing pulmonary optical density, but rimantadine was without effect. These findings correlated well with mean lung weight of each group; however, the sensitivity of the optical density technique was greater. Subjective scoring of microscopic lesions revealed differences only between infected and uninfected controls. The densitometric method offers promise as a reliable means of objectively quantifying the pulmonary response to a variety of infectious, toxic, and therapeutic agents.
Spontaneous Implantation of Antibiotic-Resistant
Enterobacteriaceae
in the Digestive Tract of Chickens in the Absence of Selective Pressure
Authors: Guillot J. F. , Chaslus-Dancla Elisabeth , Lafont J. P.
Published: June 2012

In the absence of selective pressure by antibiotics, resistant enterobacteria implanted rapidly in the intestinal tract of chickens, where these organisms subsequently persisted in high numbers. Food could be an important source of this contamination: resistant
Escherichia coli
present in small numbers in the diet became rapidly and persistently established in the gut. The human caretaker played a passive role in the spread of antibiotic-resistant bacteria between separate groups of chickens. Resistant enteric organisms colonized the gut of animals, with different population sizes. Some strains were able to reach high numbers (10
7
to 10
9
/g), and other strains established themselves at a lower level (10
3
to 10
5
/g), whereas a third type seemed to be only transient inhabitants, unable to persist.
Clinical Pharmacology of Netilmicin
Authors: Yap Boh-Seng , Stewart Dorothy , Bodey Gerald P.
Published: June 2012

Pharmacological studies of netilmicin were conducted in 30 cancer patients. After intravenous administration of 50 mg of netilmicin or gentamicin per m
2
over a 1-h period in 10 patients, the mean peak serum concentrations occurred at the end of the infusion and were 7.6 and 7.3 μg/ml, respectively. At 6 h, the mean serum concentrations of both drugs was 1.1 μg/ml. After intramuscular injection of 50 mg of netilmicin per m
2
to each of the same 10 patients, the mean peak serum concentration was 5.5 μg/ml and occurred at 1 h, and, at 6 h, the mean serum concentration was 1.4 μg/ml. The mean proportion of netilmicin excreted in urine during 6 h after intramuscular injection was 55%, and after intravenous injection it was 40.9%. Results were similar with gentamicin sulfate. After administering 60 mg of netilmicin per m
2
intravenously over 30 min every 6 h in 9 patients, the mean peak serum concentration (7.9 μg/ml) occurred at the end of the infusion. The concentration gradually decreased to below 2.0 μg/ml after 4 h. Continuous infusion of 60 mg of netilmicin per m
2
every 6 h after a 60-mg/m
2
loading dose in 11 patients produced levels consistently above 2.9 μg/ml, during the initial 6-h infusion, and levels above 2.0 μg/ml for at least 1 week.
Pharmacokinetics of Cefaclor in Normal Subjects and Patients with Chronic Renal Failure
Authors: Bloch Richard , Szwed James J. , Sloan Rebecca S. , Luft Friedrich C.
Published: June 2012

We studied the pharmacokinetics of cefaclor, a new cephalosporin antibiotic, in normal subjects and subjects with chronic renal failure. Cefaclor was largely, but not entirely, eliminated by the kidneys. The cefaclor half-life in normal subjects was 40 to 60 min; in subjects with essentially no renal function, it increased to 3 h. In normal subjects, 50 to 70% of a 250-mg dose was excreted in the urine within 8 h. The linear relationship between the elimination constant and creatinine clearance allowed the construction of a useful dosage modification nomogram.
Penicillins Activate Autolysins Extracted from Both
Escherichia coli
and
Klebsiella pneumoniae
Envelopes
Authors: Fontana Roberta , Satta G. , Romanzi C. A.
Published: June 2012

Ampicillin at a 50-μg/ml concentration effects a doubling of the autolysis rate of cell envelopes isolated from
Klebsiella pneumoniae
Mir A12. This antibiotic increases also by two- to threefold the depolymerizing activity of both
K. pneumoniae
and
Escherichia coli
crude extracts on a labeled peptidoglycan-lipoprotein complex. Several other penicillins also activate autolysins.
Actinomycin Biosynthesis by Protoplasts Derived from
Streptomyces parvulus
Authors: Hitchcock Michael J. M. , Katz Edward
Published: June 2012

Conditions are described for the formation of protoplasts from
Streptomyces parvulus
that are able to synthesize actinomycin D de novo. Antibiotic synthesis by protoplasts, in contrast to that by mycelium, was sensitive to inhibition by actinomycin D and to a decrease in sucrose concentration. On the other hand, synthesis by mycelium was much more sensitive to inhibition by amino acid analogs (
d
-valine,
cis
-3-methylproline, and α-methyl-
dl
-tryptophan). In addition, the uptake of amino acids (
l
-methionine, sarcosine, and
l
- and
d
-valine) by protoplasts was significantly lower than that by mycelium. The advantages and limitations of using protoplasts for studying in vivo actinomycin synthesis are discussed.
Alteration of Mortality and Pathogenesis of Three Experimental
Herpesvirus hominis
Infections of Mice with Adenine Arabinoside 5′-Monophosphate, Adenine Arabinoside, and Phosphonoacetic Acid
Authors: Kern Earl R. , Richards James T. , Overall James C. , Glasgow Lowell A.
Published: June 2012

The therapeutic effectiveness of adenine arabinoside 5′-monophosphate (ara-AMP), adenine arabinoside (ara-A), and phosphonoacetic acid (PAA) was compared in three experimental
Herpesvirus hominis
type 2 infections of mice. In animals inoculated with
H. hominis
by the intracerebral or intraperitoneal route, both ara-AMP and ara-A were highly effective in reducing mortality even when treatment was begun 48 to 96 h after viral inoculation. ara-AMP was the most effective in both models in that treatment could be initiated 24 to 48 h later in the course of infection than with ara-A and still confer significant protection. In mice inoculated intraperitoneally, protection due to ara-AMP therapy was associated with reduced replication of virus in visceral organs and complete inhibition of transmission of virus to the brain. PAA treatment of mice inoculated intraperitoneally was effective in reducing mortality only if initiated shortly after infection. Treatment with PAA did not reduce mortality of mice inoculated intracerebrally but did prolong the mean day of death. When mice were inoculated intranasally with
H. hominis
, none of the three drugs altered final mortality; however, treatment with ara-AMP did prolong the mean day of death. Treatment with ara-AMP effectively reduced viral replication in the lung and liver in this model infection, but failed to prevent transmission of virus through the trigeminal nerves from the nasopharynx to the brain.
Pharmacokinetics of Bacampicillin Compared with Those of Ampicillin, Pivampicillin, and Amoxycillin
Authors: Sjövall Jan , Magni Lennart , Bergan Tom
Published: June 2012

Bacampicillin, a new oral prodrug which in vivo is rapidly transformed to ampicillin, was compared with ampicillin, pivampicillin, and amoxycillin in a randomized cross-over study on 11 healthy volunteers. All drugs were given in oral doses equimolar to 400 mg of bacampicillin (800 μmol). The mean of the individual peak concentrations in serum was 8.3 μg/ml for bacampicillin, 7.1 μg/ml for pivampicillin, 7.7 μg/ml for amoxycillin, and 3.7 μg/ml for ampicillin. Furthermore, bacampicillin had a higher absorption rate than all the other drugs, although there were statistically significant differences only versus ampicillin. The peak serum levels of the individual subjects were more dispersed with ampicillin and amoxycillin, suggesting a more uniform absorption of bacampicillin and pivampicillin. The relative bioavailability of bacampicillin and pivampicillin was comparable, whereas ampicillin was only 2/3 that of the others.
Clinical Pharmacology of Mezlocillin
Authors: Issell Brian F. , Bodey Gerald P. , Weaver Susanne
Published: June 2012

Mezlocillin is a new broad-spectrum semisynthetic penicillin that has shown encouraging in vitro activity against the infecting organisms most likely to cause mortality and morbidity in cancer patients receiving chemotherapy. The serum clearances and urine recoveries of mezlocillin, ampicillin, and carbenicillin were compared after the intravenous administration of single 3-g doses. The peak mean serum concentrations of mezlocillin and carbenicillin were 269 and 278 μg/ml, respectively, whereas the peak ampicillin level was lower at 167 μg/ml. The terminal half-life of mezlocillin, 66 min, was not significantly different from those of ampicillin and carbencillin (63 and 77 min, respectively). Recoveries of mezlocillin, ampicillin, and carbenicillin from urine over 6-h periods after drug dosage were 45, 61, and 80%, respectively. A further study in 11 cancer patients examined serum maintenance levels of mezlocillin when 3-g doses were given intravenously every 4 h for at least 7 consecutive days. After 3 days of therapy, the mean serum concentrations were maintained above 50 μg/ml. Although therapeutic efficacy was not an objective of this study, all of three documented bacterial infections were cured, and no serious toxicity was encountered.
Synthesis and Antibiotic Properties of Chloramphenicol Reduction Products
Authors: Corbett Michael D. , Chipko Bernadette R.
Published: June 2012

Analogs of chloramphenicol were prepared for the first time in which the nitro group was replaced by hydroxylamine, nitroso, hydroxamic acid, methyl hydroxamate, and
O
-acetyl hydroxamate functional groups. These compounds were tested for antibiotic activity in order to determine whether the antibiotic activity of chloramphenicol is mediated by one or more of these potential metabolites of chloramphenicol. None of these analogs was as active as chloramphenicol against the four test organisms, and two of the compounds were essentially devoid of activity. The significance of these findings with regard to the importance of the nitro group to the biological activity of chloramphenicol is discussed.
Prospective Comparison of Cefoxitin and Cefazolin in Infections Caused by Aerobic Bacteria
Authors: Gurwith Marc , Albritton William , Lank Beverley , Harding Godfrey , Ronald Allan
Published: June 2012

Intravenous cefazolin and cefoxitin were compared in a prospective randomized trial in infections where the suspected pathogen was expected to be susceptible to both antibiotics. In the cefazolin group (12 patients) the diagnosis was pneumonia in 4, including 2 with pneumococcal bacteremia, soft tissue infection in 5,
Staphylococcus aureus
bacteremia in 1, acute pyelonephritis in 1, and disseminated gonococcal infection in 1. In the cefoxitin group (10 patients) the diagnosis was pneumonia in 4, including 2 with pneumococcal bacteremia, soft tissue infection in 4, acute pyelonephritis in 1, and disseminated gonococcal infection in 1. In the cefazolin group receiving an evaluable course of therapy, a good clinical response was seen in 10 of 11 patients, and a bacteriological response was seen in 5 of 7. Cefazolin failed to eradicate
S. aureus
bacteremia in 1 patient and
S. aureus
in a skin ulcer of another patient. All 10 cefoxitin patients had good clinical and bacteriological responses, but in 1 patient
S. aureus
colonization of a postoperative wound recurred after discontinuation of the drug. Side effects in both groups included skin rash, phlebitis, and elevation of the serum alkaline phosphatase. Both cefoxitin and cefazolin appeared effective in infections caused by susceptible aerobic pathogens with the possible exception of
S. aureus
, although all 11 strains of
S. aureus
isolated in this study were susceptible in vitro to both antibiotics. Cefoxitin appeared to be equivalent to cefazolin in efficacy and occurrence of side effects.
Evaluation of Miconazole Therapy in Experimental Disseminated Candidiasis in Laboratory Rats
Authors: Balk M. W. , Crumrine M. H. , Fischer G. W.
Published: June 2012

Miconazole, a broad-spectrum antimycotic agent with some antibacterial activity, has recently become available for experimental parenteral use in the United States. Its efficacy as an anticandidal drug was tested in adult Wistar rats. A previously established infectious dose of 5 × 10
6
Candida albicans
was intravenously injected into 250- to 300-g animals. This dose was fatal to 95% (20/21) of placebo-treated control animals within the 2-week postinfection observation period. Only 4% (2/53) of rats receiving intramuscular miconazole treatment died. Miconazole therapy in
Candida
-infected rats at a dosage of 50 mg/kg per day resulted in 85% survival, and, although 100 mg/kg per day was 100% efficacious, it was a relatively large volume to give intramuscularly to a rat. Therefore, 75 mg/kg per day was used as a therapeutic dose, and it gave favorable results in this study. Histological examination of all placebo-treated animals revealed
C. albicans
and a marked inflammatory response in the kidney, brain, and heart.
C. albicans
organisms were observed to be very prominent in these tissues by using the Gomori methenamine silver stain, and were cultured from these organs. Miconazole-treated rats that were killed after surviving the 2-week observation period had minimal histopathological changes, and the organisms present did not exhibit the same staining characteristics, nor were they isolated like those in the placebo-treated group. Miconazole appears to be an efficacious drug for parenteral therapy, as demonstrated in this reproducible model of disseminated candidiasis in laboratory rats, and more extensive experimental studies are indicated.
Effect of Amphotericin B Methyl Ester on Vesicular Stomatitis Virus Morphology
Authors: Jordan George W. , Humphreys Sharon , Zee Yuan Chung
Published: June 2012

The water-soluble methyl ester of amphotericin B inactivates vesicular stomatitis virus in association with morphological alterations of the envelope.
Stepwise acquisition of multiple drug resistance by beta-hemolytic streptococci and difference in resistance pattern by type
Authors: Miyamoto Y , Takizawa K , Matsushima A , Asai Y , Nakatsuka S
Published: June 2012

We collected 1,353 strains of beta-hemolytic streptococci of groups A, B, C, and G (1,176 strains of which were group A) isolated in 26 institutions throughout Japan in 1972-1974. The strains were grouped and T-typed by our specific group-and T-factor sera, and the minimal inhibitory concentrations of 10 antibiotics were assayed by the standard method. Resistant strains from the above collection were classified according to group, T-type, and drug resistance pattern. Our data on T-types for 1964-1971 and on drug resistance for 1966-1971 were used to interpret the detected long-term variations in T-type and drug resistance. The stepwise acquisition of multiple drug resistance, the difference in resistance pattern between predominant T-types, and the rarity of single-macrolide resistance were demonstrated.