bluuebunny/crossref_metadata_2025 huggingface dataset:
Chemotherapeutic Evaluation of 5-Episisomicin (Sch 22591), a New Semisynthetic Aminoglycoside
Authors: Waitz J. Allan , Miller George H. , Moss Eugene , Chiu Peter J. S.
Published: June 2012

5-episisomicin (Sch 22591) is a novel semisynthetic aminoglycoside with a spectrum and potency similar to gentamicin in its activity against susceptible bacterial strains, but with increased potency against
Pseudomonas, Providencia
, and
Proteus rettgeri
. It is also more active than tobramycin and amikacin against these last-mentioned species.

Against resistant strains, Sch 22591 is significantly more active than gentamicin or tobramycin. Against resistant gram-negative bacteria other than
Pseudomonas
, Sch 22591 has activity similar to that of amikacin, but Sch 22591 is more potent. Against
Pseudomonas
strains, it is active against most gentamicin- and tobramycin-resistant strains and is more active than the other three antibiotics. Some
Pseudomonas
strains are resistant to Sch 22591, but susceptible to amikacin. Against a selection of aminoglycoside-resistant staphylococci, Sch 22591 has very good activity against strains resistant to tobramycin, amikacin, and gentamicin. The superior in vitro potency of Sch 22591 against
Pseudomonas
has been confirmed in vivo in experimental infections in mice. Absorption in dogs is similar to that of other aminoglycoside antibiotics. The acute toxicity of Sch 22591 in mice is greater than that of gentamicin; its vestibular toxicity potential and nephrotoxicity potential in cats and rats appear to be similar to those of gentamicin.
Identification of an Antibiotic-Producing Bacterium from the Human Intestinal Tract and Characterization of Its Antimicrobial Product
Authors: Iglewski Wallace J. , Gerhardt Nancy B.
Published: June 2012

An antibiotic-producing bacterium repeatedly isolated from human feces was characterized by standard bacteriological methods. The bacterium is a gram-positive bacillus possessing morphological and physiological features similar to those of
Bacillus subtilis
, except that it lacks temperature-resistant spore formation and has peritrichous flagella. The cell-free antibiotic produced by the organism in vitro was effective against some gram-negative and gram-positive bacteria and yeast in minimum inhibitory concentration and antibiotic disk assays. The 1,200-dalton antibiotic had an optimal activity against
Proteus vulgaris
within the pH range of 5.7 to 6.8. The activity was totally destroyed by digestion with pronase and trypsin but was resistant to pepsin, chymotrypsin, papain, and nuclease digestion. In addition, the antibiotic activity against
P. vulgaris
was stable between pH 3 to 9 and within the temperature range of 20 to 100°C when tested in the fermentation medium. The activity was only partially retained by membrane filters which normally retain globular proteins of molecular weights between 500 to 10,000. Electrophoresis in phosphate buffer indicated that the activity against
P. vulgaris
had an isoelectric point of approximately 6.45. These properties are compatible with the antibiotic activity associated with a small peptide.
Synergistic Action of Amphotericin B and Antioxidants Against Certain Opportunistic Yeast Pathogens
Authors: Beggs William H. , Andrews Fred A. , Sarosi George A.
Published: June 2012

Results of earlier turbidimetric growth experiments showed that certain antioxidants prolonged the antifungal activity of amphotericin B (AB) against
Candida albicans
, presumably by retarding autoxidative destruction of the drug. Viability studies were designed to examine this in more detail. Subinhibitory concentrations of either butylated hydroxyanisole,
n
-propyl gallate, or nordihydroguaiaretic acid in combination with fungistatic levels of AB exerted synergistic fungicidal activity against two strains of
C. albicans
and one of
C. parapsilosis
. Although synergism was not seen in tests with a strain of
Torulopsis glabrata
, antioxidants prolonged the inhibitory action of AB against this organism. On the basis of these findings and other considerations that are discussed, it is suggested that stabilization of AB and the ability to act synergistically with AB represent two distinctly different effects of the antioxidants.
Mechanism of Transferable Resistance to Chloramphenicol in
Haemophilus parainfluenzae
Authors: Shaw William V. , Bouanchaud Daniel H. , Goldstein Fred W.
Published: June 2012

A clinical isolate of
Haemophilus parainfluenzae
resistant to chloramphenicol and tetracycline transferred both
cam
and
tet
determinants to
Escherichia coli
K-12 during mixed cultivation on solid media irrespective of the selection employed. The doubly resistant transconjugant was found to contain levels of the enzyme chloramphenicol acetyltransferase (CAT) comparable to those found in R plasmid-bearing chloramphenicol-resistant enteric bacteria. Purification of CAT from the transconjugant was achieved by affinity chromatography, and the electrophoretically homogeneous protein was compared with previously characterized CAT variants specified by R plasmids. Although the CAT associated with
cam
from
H. parainfluenzae
was found to be distinct from the three types described previously, its N-terminal peptide amino acid sequence was identical with that determined for a type II CAT. Attempts to demonstrate covalently closed circular deoxyribonucleic acid in the
H. parainfluenzae
donor and the
E. coli
transconjugant were unsuccessful. The
cam
and
tet
determinants were nontransmissible from
E. coli
but could be cotransferred following the introduction of a suitable conjugative plasmid.
Interaction of Neomycin with Ribosomes and Ribosomal Ribonucleic Acid
Authors: Dahlberg Albert E. , Horodyski Frank , Keller Patrick
Published: June 2012

Neomycin binds ribosomes and ribosomal ribonucleic acid (rRNA) in vivo and in vitro producing changes detectable by increases in gel electrophoretic mobility. These changes were observed in gels that contain ethylenediaminetetraacetic acid or no added magnesium ion. The progressive increase in gel electrophoretic mobility with increasing antibiotic concentrations suggests that neomycin is binding at multiple sites on RNA. The binding was reversible but sufficiently stable to survive dialysis and electrophoresis. It is proposed that bound neomycin stabilizes the ribosome and RNA structures, restricting the unfolding of the particles during electrophoresis and thus allowing for a more rapid migration in the gel. Gentamicin produced an effect similar to that of neomycin. Paromomycin, differing from neomycin by only one amino group, had considerably less effect on ribosome and rRNA mobilities. The binding of neomycin to rRNA improved the linearity of the plot of log molecular weight versus mobility and thus may be of benefit in providing a more accurate estimation of molecular weights of large RNAs.
In vitro activity of piperacillin, a new semisynthetic penicillin with an unusually broad spectrum of activity
Authors: Verbist L
Published: June 2012

The in vitro activity of piperacillin (T-1220), a new semisynthetic derivative of aminobenzylpenicillin, was investigated. The majority of streptococci and pneumococci were inhibited by 0.12 micrograms/ml; the staphylococci and enterococci were inhibited by 2 micrograms/ml. Piperacillin was slightly more active against Neisseria and Haemophilus influenzae than was ampicillin. Piperacillin was active against all members of the Enterobacteriaceae including the Klebsiella, 58% of which were inhibited by 8 micrograms/ml. The activity of piperacillin was at least equivalent, but generally superior, to that of ampicillin or carbenicillin on species susceptible to these drugs. Most striking was its activity on Pseudomonas aeruginosa: 50% were inhibited by 2 micrograms/ml, and 83% were inhibited by 4 micrograms/ml. The minimum bactericidal concentrations were very close to the minimum inhibitory concentrations, and in most species only a slight inoculum effect was observed on the minimum bacterial values except for certain P. aeruginosa strains. A complete parallel resistance exists between piperacillin and ampicillin or carbenicillin. However, the clinical importance of this is largely mitigated by the intrinsically higher activity of piperacillin.
Piperacillin, a new penicillin active against many bacteria resistant to other penicillins
Authors: Fu K P , Neu H C
Published: June 2012

The in vitro activity of piperacillin, a new semisynthetic piperazine penicillin derivative, was evaluated against 626 clinical isolates and compared with the activity of other beta-lactam antibiotics. At a concentration of 0.1 microgram/ml, piperacillin inhibited all streptococci except enterococci. Non-beta-lactamase-producing staphylococci were inhibited by 1.6 microgram or less per ml. Both beta-lactamase- and non-beta-lactamase-producing Haemophilus were inhibited by 0.1 microgram/ml. Piperacillin inhibited non-beta-lactamase-producing Escherichia coli, Salmonella, and Shigella at a concentration of 6.3 micrograms/ml, but 20% of strains of these species containing type III beta-lactamase were not inhibited by 100 micrograms/ml. Piperacillin at 25 micrograms/ml, inhibited 83% of Citrobacter, 58% of Klebsiella, 88% of Enterobacter, and 50% of indole-positive Proteus, Acinetobacter, and Providencia. At 25 micrograms/ml, piperacillin inhibited 95% of Pseudomonas aeruginosa and 78% of Bacteroides fragilis. The minimal inhibitory concentration of piperacillin against Pseudomonas was affected by increasing the inoculum size and by pH. Minimum bactericidal concentrations against Pseudomonas and Serratia often were eightfold greater than the minimum inhibitory concentrations. Piperacillin was equal in activity to ampicillin against enterococci. It was more active than carbenicillin against E. coli, Klebsiella, Enterobacter, and Bacteroides. It was the most active penicillin against Pseudomonas and inhibited many strains of Pseudomonas for which the MICs of carbenicillin were above 200 micrograms/ml. Piperacillin was hydrolyzed by many different beta-lactamases. Synergistic activity of piperacillin was demonstrated when it was combined with amikacin, gentamicin, and cefazolin against P. aeruginosa and members of the Enterobacteriaceae. No antagonism was observed when piperacillin was combined with aminoglycosides; however, antagonism was observed rarely against E. coli when piperacillin was combined with cefazolin.
Totally synthetic medium for susceptibility testing
Authors: Lawrence R M , Hoeprich P D
Published: June 2012

The results of disk diffusion and plate dilution susceptibility testing of Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis on media gelled with agar-agar or with a synthetic hydrogel were compared. Synthetic hydrogel can be combined with a totally defined synthetic amino acid medium to yield a reproducible, totally defined, synthetic solid medium without the antagonistic or booster effects of some components of agar. Such a medium could be used as a reference medium for susceptibility testing.
Susceptibility of Campylobacter fetus to twenty-two antimicrobial agents
Authors: Chow A W , Patten V , Bednorz D
Published: June 2012

In vitro susceptibility of 11 recent clinical isolates of Campylobacter fetus to 22 antimicrobial agents was determined by an agar dilution technique. Unlike most obligate anaerobic gram-negative bacilli, C. fetus isolates tested were relatively resistant to penicillin and cephalosporins, but exquisitely susceptible to tetracyclines and aminoglycosides. All strains were also inhibited at concentrations achievable in serum by clindamycin, chloramphenicol, metronidazole, carbenicillin, ticarcillin, and with rare exceptions, ampicillin. They were variably susceptible to lincomycin and erythromycin and highly resistant to vancomycin.
Central nervous system chloramphenicol concentration in premature infants
Authors: Dunkle L M
Published: June 2012

Four premature infants under 1,500 g were treated with parenteral chloramphenicol for central nervous system infections due to organisms resistant to the penicillins. Serum, cerebrospinal fluid (CSF), and ventricular fluid concentrations of chloramphenicol were measured frequently during therapy and were used to maintain drug dosages in the safe and therapeutic range. Concentrations of chloramphenicol in the lumbar CSF and ventricular fluid had a mean of 23.3 +/- 7.7 micrograms/ml, consistently greater than 45% of peak serum levels. These data show that chloramphenicol enters the CSF in both ventricular and lumbar regions in therapeutic concentrations when administered intravenously. The clinical usefulness of this drug remains to be investigated. The importance of monitoring serum drug levels during therapy is emphasized.
Susceptibility of cephalothin-resistant gram-negative bacilli to piperacillin, cefuroxime, and other selected antibiotics
Authors: George W L , Lewis R P , Meyer R D
Published: June 2012

The in vitro antibacterial activity of piperacillin and cefuroxime against 180 isolates of cephalothin-resistant Enterobacteriaceae and of piperacillin against 46 isolates of Pseudomonas aeruginosa was determined. Amikacin, gentamicin, carbenicillin, cefoxitin, and cefamandole were included for comparison. The activities of piperacillin and carbenicillin against Enterobacteriaceae were comparable. Piperacillin was appreciably more active against Pseudomonas than carbenicillin and was equivalent in activity to amikacin on a weight basis. The following beta-lactam agents were the most active against the indicated organisms (in parentheses): cefoxitin (indole-positive Proteus spp.), cefuroxime and cefoxitin, (Klebsiella spp.), piperacillin (Enterobacter spp.), cefuroxime and cefoxitin (E. coli), piperacillin and cefoxitin (Serratia spp.), and cefoxitin (Providencia spp.). Amikacin inhibited 98% of Enterobacteriaceae at clinically achievable serum levels.
Susceptibility of lipopolysaccharide-defective mutants of Pseudomonas aeruginosa strain PAO to dyes, detergents, and antibiotics
Authors: Kropinski A M , Chan L , Milazzo F H
Published: June 2012

Lipopolysaccharide-defective mutants of Pseudomonas aeruginosa strain PAO have been isolated on the basis of their resistance to lipopolysaccharide-specific bacteriophages. These mutants have been differentiated by their agglutination in NaCl and acriflavine, phage sensitivity, and chemical analysis of the lipopolysaccharides. The susceptibility of the wild-type strain and four mutants to a series of twenty-six agents, including dyes, detergents, antibiotics, and lysozyme, was examined. The roughest mutant (AK-43) exhibited increased susceptibility to sodium deoxycholate, hexadecylpyridinium chloride, benzalkonium chloride, ampicillin, penicillin G, erythromycin, colymycin, and polymyxin B. The role of cell envelope fractions in antibiotic resistance in P. aeruginosa is discussed.
Effect of benzylpenicillin on the synthesis and structure of the cell envelope of Neisseria gonorrhoeae
Authors: Goodell E W , Fazio M , Tomasz A
Published: June 2012

The effect of benzylpenicillin on the synthesis and morphology of the cell envelope of Neisseria gonorrhoeae was examined. Penicillin immediately stopped murein synthesis; it also enhanced the rate of turnover of glucosamine, but not diaminopimelic acid, in the murein. In addition, penicillin greatly increased the shedding of lipid and lipopolysaccharide into the medium. In the electron microscope, protrusions of the cell membrane were evident, as well as apparent holes in the murein cell wall. All of these changes occurred while active synthesis was taking place, before the lysis of the cells. Lysis could be prevented by growing the cells at low pH and high concentrations of Mg2+; however, the effects of penicillin on murein synthesis and turnover and on the release of lipid were not affected.
Interferon Synthesis in Human Diploid Cells Pretreated with Insulin
Authors: Azuma Masanobu , Suenaga Tohru , Yoshida Itsuro , Mizuno Fumio
Published: June 2012

Interferon production by Newcastle disease virus in human diploid (WI-38) cells was greatly reduced in the absence of serum. Pretreatment of the serum-free cells with insulin in excess of 1.2 IU/ml for 2 h before induction considerably increased the amount of interferon produced. No enhancement of interferon production was seen when the cells were exposed to insulin 2 h after induction or later. The insulin's effect persisted for at least 6 h after its removal, but not for 24 h. A possible mechanism of insulin action is discussed.
Inactivation of Herpes Simplex Viruses by Nonionic Surfactants
Authors: Asculai Samuel S. , Weis Margaret T. , Rancourt Martha W. , Kupferberg A. B.
Published: June 2012

Nonionic surface-active agents possessing ether or amide linkages between the hydrophillic and hydrophobic portions of the molecule rapidly inactivated the infectivity of herpes simplex viruses. The activity stemmed from the ability of nonionic surfactants to dissolve lipid-containing membranes. This was confirmed by observing surfactant destruction of mammalian cell plasma membranes and herpes simplex virus envelopes. Proprietary vaginal contraceptive formulations containing nonionic surfactants also inactivated herpes simplex virus infectivity. This observation suggests that nonionic surfactants in appropriate formulation could effectively prevent herpes simplex virus transmission.
Effect of Zinc and Other Chemical Agents on Foot-and-Mouth Disease Virus Replication
Authors: Polatnick Jerome , Bachrach Howard L.
Published: June 2012

Chemical agents reported to inhibit the growth of various ribonucleic acid and deoxyribonucleic acid viruses were tested against foot-and-mouth disease virus in cell culture. These included Zn
2+
, aurintricarboxylic acid, polyribocytidylic acid, polyriboinosinic acid, phosphonoacetic acid, and the viral contact inactivator
N
-methyl isatin β-thiosemicarbazone alone and with CuSO
4
. The most effective agent, Zn
2+
, inhibited foot-and-mouth disease virus production in primary calf kidney cells by 1 log unit at 0.05 mM Zn
2+
and completely at 0.50 mM. Zinc was inhibitory even when added late in infection and was nontoxic to uninfected cells as measured by protein and nucleic acid syntheses. Polyacrylamide gel patterns of [
35
S]methionine-labeled, virus-specific proteins showed increasing amounts of higher-molecular-weight material, in accord with reports that Zn
2+
inhibits post-translational cleavages of other picornavirus precursor polypeptides.
Treatment with Levamisole of Recurrent Herpes Genitalis
Authors: Chang Te-Wen , Fiumara Nicholas
Published: June 2012

A double-blind study was carried out to investigate the possibility of therapeutic effect of levamisole on recurrent progenital herpes. One hundred and nine patients, including 53 females, entered the study, but only 75 completed. Levamisole, 50 mg three times daily for 3 days, was started at the first sign of recurrence. The study period consisted of 6 visits or 12 months, whichever came first. No statistical differences were observed between levamisole and placebo groups when comparing the duration of the lesion and the degree of pain, although less pain was observed among those on levamisole. The interval between attacks was increasingly prolonged in the levamisole-treated group, and reached a significant level at the sixth visit. However, analysis on the basis of mean cumulative number of days between attacks showed no significant differences throughout the study period. Because of occasional neutropenia and generalized urticaria, and because of the absence of clear-cut clinical improvement of statistical significance, levamisole was considered of limited benefit to patients with recurrent genital herpes infection.
Methicillin-Resistant
Staphylococcus aureus
Susceptibility Testing by an Automated System, Autobac I
Authors: Cleary Timothy J. , Maurer Diane
Published: June 2012

The Autobac I system was used to evaluate the antibiotic susceptibility pattern of methicillin-resistant
Staphylococcus aureus
isolates. The results of the Autobac I were compared with the results of the disk diffusion method. The disk diffusion susceptibility pattern showed resistance to methicillin/oxacillin, penicillin, erythromycin, clindamycin, and kanamycin. All isolates were susceptible to cephalothin, chloramphenicol, tetracycline, and gentamicin. There was at least 96% agreement using the Autobac I system with all antibiotics except methicillin and clindamycin. Seventy percent of 57 isolates were recorded as susceptible to methicillin, whereas 9% had an intermediate susceptibility. With clindamycin, 14% were recorded as susceptible and 7% were recorded as intermediate. Upon prolonged incubation of the Autobac I cuvette, the agreement between the two methods was 44% for methicillin and 93% for clindamycin. Changes in the environmental conditions, such as use of 5% sodium chloride broth and a 32°C incubation temperature, did not increase the detection of methicillin-resistant isolates by the Autobac I system.
Isolation and Characterization of Multiply Antibiotic-Resistant
Clostridium perfringens
Strains from Porcine Feces
Authors: Rood Julian I. , Maher Eileen A. , Somers Eileen B. , Campos Elena , Duncan Charles L.
Published: June 2012

Multiply antibiotic-resistant strains of
Clostridium perfringens
were isolated from porcine feces. Strains that were resistant to tetracycline, erythromycin, clindamycin, and lincomycin were isolated, but no penicillin- or chloramphenicol-resistant strains were obtained. Typical minimal inhibitory concentrations for resistant strains were 16 to 64 μg of tetracycline per ml, 64 to >128 μg of erythromycin per ml, ≥128 μg of lincomycin per ml, and 16 to 128 μg of clindamycin per ml. Resistance to erythromycin was always associated with resistance to lincomycin and clindamycin. Minimal inhibitory concentrations were determined for 258 strains from six farms that used antibiotics in their feeds and 240 strains from five farms that did not use antibiotics. The results show that 77.9 and 22.7% of the strains from the former farms were resistant to tetracycline and erythromycin-clindamycin-lincomycin, respectively. The comparable data from the latter farms were 25.0 and 0.8%, respectively. Agarose gel electrophoresis failed to reveal a plasmid band that was common to the resistant strains but absent in the susceptible strains. Attempts to transfer tetracycline, erythromycin, and clindamycin resistance from one strain, CW459, were not successful. Antibiotic-susceptible mutants were not isolated from this strain, despite the use of a variety of curing agents.
Cofactor Role of Iodide in Peroxidase Antimicrobial Action Against
Escherichia coli
Authors: Thomas Edwin L. , Aune Thomas M.
Published: June 2012

The mechanism of antimicrobial activity of the peroxidase-hydrogen peroxide (H
2
O
2
)-iodide (I
−
) system was investigated. Inhibition of respiration and loss of viability of
Escherichia coli
were used as measures of antimicrobial activity. Because the bacteria destroyed H
2
O
2
, peroxidase antimicrobial action depended on the competition for H
2
O
2
between the bacteria and the peroxidase. Utilization of H
2
O
2
by the peroxidase was favored by (i) increasing either the peroxidase or the I
−
concentration, so as to increase the rate of oxidation of I
−
, (ii) lowering the temperature to lower the rate of destruction of H
2
O
2
by the bacteria, and (iii) adding H
2
O
2
in small increments so as to avoid a large excess of H
2
O
2
relative to I
−
. When utilization of H
2
O
2
by the peroxidase system was favored, the peroxidase system and iodine (I
2
) were equivalent. That is, antimicrobial action per mole of H
2
O
2
equaled that per mole of I
2
. Also, identical antimicrobial action was obtained either by incubating the bacteria directly with the peroxidase system or by preincubating the peroxidase system so as to form I
2
and then adding the bacteria. On the other hand, peroxidase antimicrobial action could be obtained at low I
−
concentrations. These I
−
concentrations were lower than the concentration of I
2
that was required for antimicrobial action. It is proposed that peroxidase-catalyzed oxidation of I
−
yields I
2
, which reacts with bacterial components to yield the oxidized components and I
−
. The I
−
that is released can be reoxidized and participate again in the oxidation of bacterial components. In this way, I
−
acts as a cofactor in the peroxidase-catalyzed oxidation of bacterial components.
Antimalarial Activities of Various 4-Quinolinemethanols with Special Attention to WR-142,490 (Mefloquine)
Authors: Schmidt L. H. , Crosby Ruth , Rasco Jane , Vaughan Dennis
Published: June 2012

Pilot appraisals of the activities of a selected group of 4-quinolinemethanols against acute
Plasmodium falciparum
infections in owl monkeys indicated that compounds of this class are equally active against infections with chloroquine-resistant and chloroquine-susceptible strains and that this efficacy is not compromised by concomitant resistance to pyrimethamine, and in addition, identified three derivatives with outstanding activity (WR-226,253; WR-142,490; and WR-184,806). WR-142,490, the second 4-quinolinemethanol evaluated in the above model, was five times as active as chloroquine against infections with the chloroquine-susceptible, pyrimethamine-resistant strain and had a much larger therapeutic index. Expanded evaluations designed to support projected studies in human volunteers provided full confirmation of the pilot appraisals and in addition showed: (i) that the activity of WR-142,490 was a function of the total dose delivered, single doses being as effective as three or seven fractional doses administered over as many days; (ii) that intravenous administration of this agent was feasible and effective; and (iii) that the compound was at least as active against infections with
P. vivax
as against infections with
P. falciparum
. Companion studies in rhesus monkeys infected with
P. cynomolgi
showed that WR-142,490 lacked prophylactic or radical curative activity, but that it was as effective as chloroquine as a companion to primaquine in a combination curative drug regimen. The results of human volunteer and field trials agree well with comparable segments of these experimental evaluations.
Comparison of Netilmicin with Gentamicin in the Therapy of Experimental
Escherichia coli
Meningitis
Authors: Scheld W. Michael , Brown Robert S. , Sande Merle A.
Published: June 2012

Netilmicin (SCH 20569), a new broad-spectrum aminoglycoside derived from sisomicin, was compared with gentamicin in the therapy of experimental
Escherichia coli
meningitis in rabbits. Meningitis was produced in 48 animals by the intracisternal inoculation of 10
5
E. coli
colony-forming units. The minimum bactericidal concentration was 2 μg/ml against the test strain for both gentamicin and netilmicin. The two aminoglycosides demonstrated comparable penetration into the cerebrospinal fluid (CSF). The mean percent penetration [(CSF concentration/serum concentration) × 100%] was 22.5 ± 6.0 and 20.6 ± 7.2 for netilmicin and gentamicin, respectively (
P
= 0.18). However, netilmicin achieved bactericidal activity in the CSF at lower levels than did gentamicin. When mean CSF concentrations ranged from 4 to 8 μg/ml, mean CSF bacterial titers decreased 2.98 logs in rabbits treated with netilmicin but only 0.16 log in rabbits treated with gentamicin. A 2-log decrease in CSF bacterial counts was produced by a mean CSF concentration of 1.4 μg of netilmicin per ml as compared to 14.1 μg of gentamicin per ml. Because of its reduced toxicity and greater in vivo bactericidal activity, netilmicin may offer an advantage over gentamicin in the therapy of gram-negative bacillary meningitis.
Iodometric Assay Method for Beta-Lactamase with Various Beta-Lactam Antibiotics as Substrates
Authors: Sawai Tetsuo , Takahashi Ikuko , Yamagishi Saburo
Published: June 2012

The rapid fixed-time assay for penicillinase was modified for measuring β-lactamase activity with twelve substrates, i.e., benzylpenicillin, ampicillin, cloxacillin, methicillin, carbenicillin, cefazolin, cephalothin, cephaloglycin, cephalexin, cephalosporin C, 7-aminocephalosporanic acid, and cefoxitin. The method depends upon the reduction of iodine by the hydrolyzed substrate. Determined experimentally, 1 mol of hydrolyzed penicillins consumed 3.4 to 4.0 mol of iodine (I
2
). Iodine consumption of hydrolyzed cephalosporins varied widely from 1.7 for cephalothin to 3.7 for cefazolin. The method is useful for routine assay of β-lactamase activity with various substrates.
Effect of an Interferon Inducer, 9-Methylstreptimidone, on
Candida albicans
Infection in Mice
Authors: Umenai Takusei , Suzuki Fujio , Ishida Nakao
Published: June 2012

The protective effect of an interferon inducer with a low molecular weight, 9-methylstreptimidone (9-MS), against
Candida albicans
infection in mice was investigated. The antibiotic was effective only when given prophylactically. When administered in such a manner, the growth of
C. albicans
in the kidneys and brain was inhibited at the initial stage of infection. The growth of
C. albicans
was not inhibited by the antibiotic in vitro, and no antifungal effect was obtained in a preparation containing induced interferon. These results suggest that the antifungal action of 9-methylstreptimidone in mice might be manifested not by direct antifungal activity but rather by a host-mediated activity that excludes interferon-inducing capability.
Clinical and Laboratory Investigation of Cefamandole in Infections of Infants and Children
Authors: Azimi Parvin H.
Published: June 2012

Forty-seven infants and children with a variety of infections including bacteremia, ethmoiditis, and periorbital cellulitis, soft tissue infection, pneumonia, and lymphadenitis were treated with intravenous cefamandole. The infections were due to
Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae
, and
Haemophilus influenzae
. The clinical response was prompt, and, with the exception of two cases who developed skin rash, significant side effects were not noted. In vitro cefamandole was very effective in inhibiting the growth of
H. influenzae
, including ampicillin-resistant isolates.
Susceptibility of
Haemophilus influenzae
Type b to Rifampin and Sulfisoxazole
Authors: Bannatyne Robert M. , Cheung Rose
Published: June 2012

A total of 100 and 97% of
Haemophilus influenzae
type b strains from major infections were susceptible, respectively, to levels of rifampin and sulfisoxazole attainable in saliva. It is theoretically feasible to eliminate
Haemophilus influenzae
from the nasopharynx with these drugs.
Chloramphenicol Acetyltransferase of
Bacteroides fragilis
Authors: Britz M. L. , Wilkinson R. G.
Published: June 2012

Chloramphenicol-resistant strains of
Bacteroides fragilis
(minimum inhibitory concentration, 12.5 μg/ml) were isolated from a stool specimen which contained multiply resistant
Escherichia coli
. The enzyme responsible for resistance, chloramphenicol acetyltransferase, was produced constitutively by these strains; the specific activity was 10-fold lower than that of the
E. coli
enzymes. Similar activity was not detected in susceptible
B. fragilis
strains, nor could it be induced by growth in the presence of chloramphenicol or by mutagenesis. The enzyme had a pH optimum of 7.8 and a molecular weight of approximately 89,000. The

K
m

for chloramphenicol was 5.2 μM, and the enzyme was sensitive to inhibition by 5,5′-dithiobis-2-nitrobenzoic acid. The enzyme produced by an
E. coli
strain isolated from the same specimen had a similar

K
m

and sensitivity to 5,5′-dithiobis-2-nitrobenzoic acid.
Dihydrofolate Reductases in Some Folate-Requiring Bacteria with Low Trimethoprim Susceptibility
Authors: Then Rudolf L. , Riggenbach Hans
Published: June 2012

Dihydrofolate reductases from the folate-requiring strains
Streptococcus faecalis
ATCC 8043,
Lactobacillus casei
ATCC 7496, and
Pediococcus cerevisiae
ATCC 8081, as well as from
Lactobacillus arabinosus
, which is not dependent on exogenous folate, were isolated, and their properties were compared to reductases of
Escherichia coli
B,
Staphylococcus aureus
, and rat liver reductase. An inhibition profile with six different inhibitors revealed significant differences among all enzymes. All lactobacilli reductases are less sensitive to trimethoprim than the enzymes of
E. coli
and
S. aureus
, the reductase of
P. cerevisiae
requiring a concentration at least 1,000 times higher for 50% inhibition. Inhibition of growth of
S. faecalis
by pyrimethamine and 2,4-diamino-6,7-diisopropyl-pteridine was seen to be much stronger than was predicted from the enzymatic data.
In Vitro Studies with Ambruticin, a New Antifungal Antibiotic
Authors: Shadomy Smith , Dixon Dennis M. , Espinel-Ingroff Ana , Wagner Gerald E. , Yu Hung Pui , Shadomy H. Jean
Published: June 2012

The in vitro antifungal inhibitory activities of ambruticin and of various antifungal drugs of choice against 190 fungal pathogens representative of the major human mycoses were compared using a modification of the ICS agar dilution technique. Ambruticin compared favorably with amphotericin B and miconazole when tested against the dimorphic pathogens
Coccidioides immitis, Histoplasma capsulatum
, and
Blastomyces dermatitidis
and against
Aspergillus fumigatus
. Miconazole was the most active compound against
Sporothrix schenckii, Allescheria (Petriellidium) boydii
, and selected dematiaceous fungi, with ambruticin giving minimal inhibitory, concentrations from 3- to 74-fold higher. Ambruticin compared unfavorably with amphotericin B and 5-fluorocytosine when tested against
Candida
and
Torulopsis
species. Ambruticin was not as active in vitro as tolnaftate when tested against the three genera of dermatophytic fungi, but compared favorably with miconazole.
Pharmacokinetics of Cefaclor in Patients with End Stage Renal Disease and During Hemodialysis
Authors: Berman S. J. , Boughton W. H. , Sugihara J. G. , Wong E. G. C. , Sato M. M. , Siemsen A. W.
Published: June 2012

A single 1.0-g dose of cefaclor administered to patients with stable end stage renal disease whose creatinine clearances were <5 ml/min produced a mean peak serum concentration of 48.3 ± 19.8 μg/ml. The half-life was 2.3 ± 0.3 h. Hemodialysis shortened the half-life of a similar dose to 1.6 ± 0.3 h. Approximately one-third (340 mg) of the administered drug was recovered in the dialysate. Multiple doses of 500 mg every 6 h between hemodialysis sessions produced effective serum concentrations and no bioassay evidence of drug accumulation.
Pharmacokinetics of Cefamandole in Infants and Children
Authors: Walker Stuart H. , Gahol Victoria P.
Published: June 2012

In infants less than 3 months of age, the serum concentration of cefamandole during therapy was higher and more prolonged than that in children older than 1 year. A dosage of 37 mg/kg administered intravenously at 6-h intervals provided a serum concentration in excess of the minimum inhibitory concentrations of common bacterial pathogens for 4 h, and in young infants for 5 h, after dosing.
Beta-Lactamase Stability of HR 756, a Novel Cephalosporin, Compared to That of Cefuroxime and Cefoxitin
Authors: Fu Kwung P. , Neu Harold C.
Published: June 2012

The stability to β-lactamase hydrolysis of HR 756, a new cephalosporin antibiotic, was compared to the β-lactamase stability of cefoxitin and cefuroxime. HR 756, cefoxitin, and cefuroxime were not hydrolyzed by Richmond type I, III, IV, and V β-lactamases. Antibacterial activity of HR 756 correlated well with resistance to β-lactamase hydrolysis except against
Pseudomonas aeruginosa
. HR 756, cefoxitin, and cefuroxime inhibited type I β-lactamases, but not type III, IV, or V enzymes. HR 756 was the most active inhibitor.
Partial Characterization of R-Plasmids from
Pasteurella multocida
Isolated from Turkeys
Authors: Berman Stephen M. , Hirsh Dwight C.
Published: June 2012

Pasteurella multocida
, isolated from turkeys during an outbreak of septicemic disease (“fowl cholera”), was found to be resistant to tetracycline, streptomycin, and sulfonamides. Agarose gel electrophoretic analysis of DNA from these isolates indicated the presence of extrachromosomal elements. Plasmid DNA was isolated by cesium chloride-ethidium bromide density centrifugation.
Escherichia coli
was transformed to antimicrobic resistance with this DNA. Two plasmids were isolated. One of these plasmids had a buoyant density of 1.7158 g/cm
3
(56.9 mol% guanine plus cytosine) and a molecular weight of 4.4 × 10
6
and conferred resistance to tetracycline, streptomycin, and sulfonamides. The other, having a buoyant density of 1.7198 g/cm
3
(61 mol% guanine plus cytosine) and a molecular weight of 3.44 × 10
6
, conferred resistance to streptomycin and sulfonamides. Streptomycin resistance was mediated by streptomycin phosphotransferase. Compatibility group testing indicated that neither plasmid belonged to any of 13 compatibility groups (of conjugal plasmids). Both plasmids were also found to be compatible with three small, nonconjugative resistance plasmids.
Effect of Different Lots of Mueller-Hinton Agar on the Interpretation of the Gentamicin Susceptibility of
Pseudomonas aeruginosa
Authors: Pollock Helen M. , Minshew Barbara H. , Kenny Margaret A. , Schoenknecht Fritz D.
Published: June 2012

Population distributions and quality control data for strains of
Pseudomonas aeruginosa
tested for gentamicin susceptibility on six lots of Mueller-Hinton agar were analyzed. The lots of agar were used in three University of Washington hospitals from April 1975 through October 1977. The analyses indicated that the performance of members of the
P. aeruginosa
populations in each hospital closely followed the performance of the quality control strain,
P. aeruginosa
ATCC 27853, when tested on each lot of Mueller-Hinton medium. The variability of zone diameters with the
P. aeruginosa
populations and the quality control strain indicated that a fixed indeterminate range (13 to 16 mm) of gentamicin susceptibility was not applicable to these organisms as it was with the
Enterobacteriaceae
. Variability in gentamicin susceptibility results was demonstrated in both minimal inhibitory concentration and disk diffusion tests when eight selected
P. aeruginosa
strains and the quality control strain were tested on each lot of medium. This variation in susceptibility to gentamicin was not related to the total Ca
2+
, Mg
2+
, or Zn
2+
content of each lot of medium. The data demonstrated that a moving indeterminate range of gentamicin susceptibility, 3 to 6 mm below the mean zone diameter of the quality control strain, was a suitable criterion for strains tested on a single medium lot. These results illustrate the importance of defining stringent performance standards for media used in the susceptibility testing of
P. aeruginosa
with gentamicin and other aminoglycoside antibiotics.
In Vitro Susceptibility of 30 Strains of
Chlamydia trachomatis
to Rosamicin
Authors: Smith Thomas F. , Washton Harriet E.
Published: June 2012

A total of 13 of 30 clinical isolates of
Chlamydia trachomatis
were susceptible in vitro to 0.01 μg of rosamicin per ml. Only two of these strains were susceptible to tetracycline or erythromycin at this level. The results suggest that rosamicin may be useful for the treatment of chlamydial urethritis.
Amoxicillin Entry into Human Cerebrospinal Fluid: Comparison with Ampicillin
Authors: Clumeck N. , Thys J. P. , Vanhoof R. , Vanderlinden M. P. , Butzler J. P. , Yourassowsky E.
Published: June 2012

The entry of amoxicillin and ampicillin into cerebrospinal fluid (CSF) of humans was studied in the absence of meningeal inflammation. Twelve volunteers received 33 mg of amoxicillin per kg intravenously over 30 min and nine volunteers received 33 mg of ampicillin per kg. The CSF specimens were sampled at 1, 2, and 4 h after the beginning of the infusion. Blood samples were obtained at the end of the infusion and at 45, 60, 90, 120, 180, and 240 min after the beginning of the infusion. Amoxicillin and ampicillin were both detected in the CSF. Ampicillin tended to give higher CSF levels than amoxicillin, although the difference was small. Serum concentrations of ampicillin equaled those of amoxicillin.
Microbial Transformations of Natural Antitumor Agents:
O
-Demethylation of Vindoline by
Sepedonium chrysospermum
Authors: Wu Geng-Shuen , Nabih Thomas , Youel Leisa , Peczynska-Czoch Wanda , Rosazza John P.
Published: June 2012

Vindoline (
1a
) was transformed to
O
-demethylvindoline (
1b
) by
Sepedonium chrysospermum
ATCC 13378 in 33% yield. Thin-layer and high-pressure liquid chromatographic methods distinguished
1b
from previously reported microbial metabolites of vindoline. The structural proof of
1b
was based on its mass spectral fragmentation pattern and on its chemical and nuclear magnetic resonance spectral properties.
Importance of Antimicrobial Susceptibility Testing of
Streptococcus pneumoniae
Authors: Tarpay Martha
Published: June 2012

Six of 36 strains of
Streptococcus pneumoniae
isolated in our laboratory during 1977 showed relative resistance to penicillin G. This level of resistance was detectable only by the broth dilution method. Using the disk diffusion method, all six strains appeared susceptible (zone size > 29 mm).
Artifactual Depression of Serum Glutamic Oxaloacetic Transaminase by Metronidazole
Authors: Rissing J. Peter , Newman Cheryl , Moore William L.
Published: June 2012

Eighteen patients developed abnormally low serum glutamic oxaloacetic transaminase values during metronidazole therapy. Metronidazole absorbs at 340 nm, simulating reduced nicotinamide adenine dinucleotide, which is the final colorimetric product of the serum glutamic oxaloacetic transaminase assay.
Minimum Bactericidal Concentration of Sulfamethoxazole-Trimethoprim for
Haemophilus influenzae
: Correlation with Prophylaxis
Authors: Kirven Linda A. , Thornsberry Clyde
Published: June 2012

The inability of sulfamethoxazole-trimethoprim (SXT) to eradicate
Haemophilus influenzae
nasopharyngeal carriage in all asymptomatic patients in closed populations was examined in vitro. A broth medium was adapted for susceptibility testing of
H. influenzae
which permitted us to determine minimum inhibitory concentrations and minimum bactericidal concentrations (MBCs). The minimum inhibitory concentrations were all low, but the MBCs were bimodally distributed. Trimethoprim alone or the combination SXT either was bactericidal for
H. influenzae
isolates at low concentrations (i.e., low MBCs) similar to minimum inhibitory concentrations or showed no bactericidal activity (i.e., high MBCs). If trimethoprim was bactericidal when tested alone against
H. influenzae
, then the combination SXT was also bactericidal.
H. influenzae
carriage could not be eradicated from asymptomatic patients with SXT therapy when that combination was not bactericidal for these isolates in vitro.
H. influenzae
carriage was eradicated from patients when the activity of SXT was bactericidal in vitro.
H. influenzae
strains that are not killed by trimethoprim or SXT seem to occur at random.
Comparison of 5-Episisomicin (Sch 22591), Gentamicin, Sisomicin, and Tobramycin in Treatment of Experimental
Pseudomonas
Infections in Mice
Authors: Goering Richard V. , Sanders Christine C. , Sanders W. Eugene
Published: June 2012

Sch 22591 (5-episisomicin), gentamicin, sisomicin, and tobramycin were compared for their ability to protect mice from lethal intraperitoneal challenge with 12
Pseudomonas
strains, all susceptible to each of the aminoglycosides (minimal inhibitory concentrations and minimal bactericidal concentrations were ≤6.2 μg/ml). Median 50% protective doses were 5.8, 6.4, 7.7, and 17.8 mg/kg for Sch 22591, tobramycin, sisomicin, and gentamicin, respectively. Those for Sch 22591 were significantly lower than gentamicin in five protection tests and significantly lower than both gentamicin and tobramycin in one test. Microbial analysis of the therapeutic effect indicated that protection from lethality by each of the four aminoglycosides was associated with either a complete eradication or a reduction in the number of challenge bacteria in both the heart blood and peritoneum. In rare instances, challenge isolates exhibiting decreased susceptibility to one or more of the aminoglycosides were recovered from animals. However, this in vivo selection of resistance did not appear related to either the aminoglycoside used in therapy or the outcome of therapy, and resistant isolates were recovered as frequently from untreated animals as from those receiving one of the four aminoglycosides.
UK-18,892: Resistance to Modification by Aminoglycoside-Inactivating Enzymes
Authors: Andrews R. J. , Brammer K. W. , Cheeseman H. E. , Jevons S.
Published: June 2012

UK-18,892, a new semisynthetic aminoglycoside, was active against bacteria possessing aminoglycoside-inactivating enzymes, with the exception of some known to possess AAC(6′) or AAD(4′) enzymes. This activity has been rationalized by using cell-free extracts of bacteria containing known inactivating enzymes, where it was shown that UK-18,892 was not a substrate for the APH(3′), AAD(2″), AAC(3), and AAC(2′) enzymes. It was also demonstrated that UK-18,892 protected mice against lethal infections caused by organisms possessing aminoglycoside-inactivating enzymes.
In Vitro and In Vivo Activity of a Synthetic Halogenated Quinoline Against
Cryptococcus neoformans
Authors: Hubbard J. C. , Hall Nancy K. , Larsh Howard W.
Published: June 2012

The minimum inhibitory concentrations of a halogenated quinoline, 3-amino-7-chloro-3,4-dihydro-1-hydroxycarbostyril (CBS), against nine clinical strains of
Cryptococcus neoformans
were determined by in vitro testing. The CBS was fungistatic at a minimum concentration of 0.2 μg/ml at 48 h for several strains. In vivo toxicity studies were carried out in mice. Mice were also infected with
C. neoformans
strain Price and injected with various concentrations of CBS. Mean life expectancy of treated groups of animals was increased over infected untreated controls.
Double-Blind Clinical Trials of Oral Cyclacillin and Ampicillin
Authors: Gold Jerome A. , Hegarty C. Paul , Deitch Marc W. , Walker Barry R.
Published: June 2012

A double-blind study was performed to compare the clinical response and the incidence of side effects in 2,581 patients administered ampicillin or cyclacillin for infections of the genitourinary or respiratory tract, infections of the skin and soft tissues, or for otitis media. There was no significant difference in clinical response and bacterial eradication. All side effects, including diarrhea and skin rash, were approximately twice as frequent in patients treated with ampicillin.
Methicillin-Resistant Strains of
Staphylococcus aureus
Phage Type 92
Authors: Schaefler S. , Perry W. , Jones D.
Published: June 2012

Methicillin-resistant (Mec
r
) strains of
Staphylococcus aureus
received for phage typing from several hospitals in New York City were resistant to the international set of typing phages but susceptible to experimental phage 92. Subsequently, strains of type 92 were detected in two outbreaks with Mec
r
strains in two other locations in the United States. In all instances, type 92 was predominant among the Mec
r
strains isolated in each hospital. With the exception of one strain, the methicillin resistance of the Mec
r
strains investigated was homogeneous. In most instances, isolates from the same hospital were closely similar in their antibiotic resistance patterns. The strains isolated in New York City could be divided into three groups by the host range of their lysogenic phages and by antigenic structure. Transduction experiments indicated that the transfer of chromosomal tetracycline resistance from Mec
r
strains into a strain susceptible to several international typing phages renders the latter nontypable. However, the acceptor strain remains susceptible to experimental phages 92 and 88. Transduction of methicillin resistance had no effect on the phage susceptibility of the acceptor strain. It is possible that the presence of chromosomal tetracycline resistance is a determining factor in the phage susceptibility of Mec
r
strains isolated in New York City.