bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative Inhibition of β-Lactamases by Novel β-Lactam Compounds
Authors: Fu Kwung P. , Neu Harold C.
Published: June 2012

The β-lactamase-inhibiting activity of CP-45,899, 3,3-dimethyl-7-oxo-4-thia-1-azabicylo(3,2,0)heptane-2-carboxylic acid, 4,4-dioxide [2S-(2α,5α)], was investigated and compared with the β-lactamase-inhibiting activity of clavulanic acid and dicloxacillin. CP-45,899 was an effective inhibitor of
Staphylococcus aureus
β-lactamase and of those β-lactamases of gram-negative bacteria which are primarily active against penicillins or equally active against penicillins and cephalosporins. The reaction of CP-45,899 with β-lactamases was a concentration- and time-dependent event. CP-45,899 acted as a competitive inhibitor of plasmid-mediated
S. aureus, Escherichia coli
, and
Shigella sonnei
β-lactamases and inducible
Klebsiella
β-lactamase. CP-45,899 was a poor inhibitor of inducible or constitutive chromosomally mediated β-lactamases of indole-positive
Proteus, Citrobacter
, and
Enterobacter
. CP-45,899 had lower kinetic constants for inhibition of hydrolysis than did clavulanic acid against many of the β-lactamases which both inhibited.
Avermectins, New Family of Potent Anthelmintic Agents: Producing Organism and Fermentation
Authors: Burg Richard W. , Miller Brinton M. , Baker Edward E. , Birnbaum Jerome , Currie Sara A. , Hartman Robert , Kong Yu-Lin , Monaghan Richard L. , Olson George , Putter Irving , Tunac Josefino B. , Wallick Hyman , Stapley Edward O. , Oiwa Ruiko , Ōmura Satoshi
Published: June 2012

The avermectins are a complex of chemically related agents which exhibit extraordinarily potent anthelmintic activity. They are produced by a novel species of actinomycete, NRRL 8165, which we have named
Streptomyces avermitilis
. The morphological and cultural characteristics which differentiate the producing organism from other species are described. The avermectins have been identified as a series of macrocyclic lactone derivatives which, in contrast to the macrolide or polyene antibiotics, lack significant antibacterial or antifungal activity. The avermectin complex is fully active against the gastrointestinal nematode
Nematospiroides dubius
when fed to infected mice for 6 days at 0.0002% of the diet. Fermentation development, including medium modification and strain selection, resulted in increasing the broth yields from 9 to 500 μg/ml.
Avermectins, New Family of Potent Anthelmintic Agents: Efficacy of the B
1a
Component
Authors: Egerton J. R. , Ostlind D. A. , Blair L. S. , Eary C. H. , Suhayda D. , Cifelli S. , Riek R. F. , Campbell W. C.
Published: June 2012

When given to sheep as a single oral dose at 0.1 mg/kg, the B
1a
component of the avermectins caused a reduction of >95% in the numbers of
Haemonchus contortus, Ostertagia circumcincta
(including inhibited L
4
larvae),
Trichostrongylus axei, Trichostrongylus colubriformis, Cooperia oncophora
, and
Oesophagostomum columbianum
. When given to cattle as a single oral dose at 0.1 mg/kg, avermectin B
1a
was >95% effective in reducing the numbers of
Haemonchus placei, Ostertagia ostertagi
(including inhibited L
4
larvae),
T. axei, T. colubriformis, C. oncophora, Cooperia punctata, Oesophagostomum radiatum
, and
Dictyocaulus viviparus
. Avermectin B
1a
was similarly effective, with the exception of a detectable loss in activity against adult
C. oncophora
, when administered to cattle as a parenteral injection. Some of these ruminant parasites were fully susceptible to dosages of avermectin B
1a
at 0.025 mg/kg, e.g.,
D. viviparus, O. radiatum, O. ostertagi
, and
H. contortus
. Avermectin B
1a
removed 83 to 100% of
Ancylostoma caninum
from dogs given a single oral dose of 0.003 to 0.005 mg/kg. The poultry nematodes
Capillaria obsignata
and immature
Ascaridia galli
were effectively removed by avermectin B
1a
at 0.05 and 0.1 mg/kg, respectively, but 0.1 mg/kg was not effective for
Heterakis gallinarum
. Thus, the avermectins would appear to have unprecedented potency and spectrum of biological activity.
Effect of Ampicillin and Chloramphenicol Alone and in Combination on Ampicillin-Susceptible and -Resistant
Haemophilus influenzae
Type B
Authors: Cole F. Sessions , Daum Robert S. , Teller Lynn , Goldmann Donald A. , Smith Arnold L.
Published: June 2012

To evaluate ampicillin (Amp) and chloramphenicol (Cm) alone and in combination against
Haemophilus influenzae
type b, we examined the viability of 5 log
10
colony-forming units (CFU) of early-log-phase organisms per ml after 4 and 8 h of incubation with the drug(s). Nine Amp-susceptible (Amp
s
) and five Amp-resistant (Amp
r
) systemic isolates were examined. Antibiotic concentrations included: the minimum inhibitory concentration (MIC) of Amp, 50% of the MIC of Amp, 25% of the MIC of Amp, the MIC of Cm, 50% of the MIC of Cm, 25% of the MIC of Cm, and nine combinations of these concentrations. Both Amp and Cm at their MIC significantly reduced bacterial titers of Amp
s
H. influenzae
type b after 8 h of incubation (1.36 and 1.47 log
10
CFU/ml, respectively; both
p
< 0.01); only Cm at its MIC significantly reduced the number of viable organisms after 4 h (0.91 log
10
CFU/ml;
P
< 0.001). With Amp
r
organisms, significant reductions in mean bacterial titers occurred after 4 and 8 h of incubation in the presence of Amp at its MIC (1.66 and 2.06 log
10
CFU/ml, respectively; both
P
< 0.02); smaller but significant reductions were noted after 4 and 8 with Cm at its MIC (0.56 and 0.87 log
20
CFU/ml, respectively; both
P
< 0.025). Antagonism with Amp
s
or Amp
r
strains was not seen. We conclude that combinations of Amp and Cm have indifferent effects on Amp
s
and Amp
r
H. influenzae
type b.
Role of Vancomycin as a Component of Oral Nonabsorbable Antibiotics for Microbial Suppression in Leukemic Patients
Authors: Bender John F. , Schimpff Stephen C. , Young Viola Mae , Fortner Clarence L. , Brouillet Mary D. , Love Lillian J. , Wiernik Peter H.
Published: June 2012

A total of 38 adult patients with acute leukemia who were undergoing remission induction chemotherapy in regular patient rooms were randomly allocated to one of two oral nonabsorbable antibiotic regimens for infection prophylaxis (gentamicin, vancomycin, and nystatin [GVN] or gentamicin and nystatin [GN]) to evaluate whether vancomycin was a necessary component. The patient population in both groups were comparable. Tolerance to GVN was less than GN but compliance was approximately equal (>85% in both groups). Patients receiving vancomycin demonstrated greater overall alimentary tract microbial suppression; however, acquisition of potential pathogens was approximately equal in both groups. The incidence of bacteremia, as well as the overall incidence of infection as related to the number of days at various granulocyte levels, was also approximately equal in both groups. Group D
Streptococcus
species were poorly suppressed by GN compared with GVN, although no patient developed an infection with these organisms. Colonization by newly acquired gram-negative bacilli was significantly less in the GN group (GN, 3 colonizations; GVN, 13 colonizations;
P
< 0.01). It is concluded that vancomycin may be safely eliminated from the GVN regimen provided microbiological data is monitored to detect resistant organisms.
Photochemical Inactivation of Deoxyribonucleic and Ribonucleic Acid Viruses by Chlorpromazine
Authors: Hanson Carl Veith
Published: June 2012

Chlorpromazine, a widely used tranquilizing drug of the phenothiazine group, was found to be a very potent photochemical inactivator of both deoxyribonucleic acid and ribonucleic acid viruses in the presence of long-wave ultraviolet light (320 to 380 nm). Neither the light alone nor chlorpromazine alone caused any appreciable inactivation. The known chlorpromazine photoreactions with nucleic acids are somewhat similar to those of psoralen (furocoumarin) derivatives. As in the case of the psoralens, chlorpromazine is capable of photoinactivating viruses totally within a few minutes under near-physiological or other gentle conditions. The antiviral effects of the chlorpromazine photoreaction could make it valuable for the development of inactivated viral vaccines as well as for use in the photochemotherapy of viral dermatoses.
Antifungal Activity of Tioconazole (UK-20,349), a New Imidazole Derivative
Authors: Jevons S. , Gymer G. E. , Brammer K. W. , Cox D. A. , Leeming M. R. G.
Published: June 2012

Tioconazole (UK-20,349), a new antifungal imidazole derivative, was compared with miconazole for activity in vitro against
Candida
spp.,
Torulopsis glabrata, Cryptococcus neoformans, Aspergillus
spp., and dermatophyte fungi (
Trichophyton
spp. and
Microsporum
spp.). Tioconazole was more active than miconazole against all the fungal species examined except
Aspergillus
, against which both agents showed similar activity. Both tioconazole and miconazole inhibited the growth of all fungi examined at concentrations well below their quoted minimum inhibitory concentrations. Their activity against fungi in vivo was investigated in mice infected systemically with
Candida albicans
. Both agents significantly reduced the numbers of viable
Candida
cells recoverable from the kidneys of infected animals, with tioconazole producing a generally more marked reduction. After administration of a single oral dose (25 mg/kg) to beagle dogs or white mice, higher and more sustained circulating levels of bioactive drug were detectable of tioconazole than of miconazole. These observations suggest that tioconazole may have potential in the treatment of both superficial and systemic mycoses in humans.
Effects of Miconazole and Dodecylimidazole on Sterol Biosynthesis in
Ustilago maydis
Authors: Henry Matthew J. , Sisler Hugh D.
Published: June 2012

Miconazole at minimal fungitoxic concentrations inhibits ergosterol biosynthesis in sporidia of
Ustilago maydis
by interference with sterol C14 demethylation. The action is analogous to that of the fungicides triarimol and fenarimol. The fungicide 1-dodecylimidazole at low concentrations (0.1 to 0.25 μg/ml) inhibits sterol C14 demethylation; however, at higher concentrations (1.0 μg/ml or greater) it also inhibits 2,3-oxidosqualene cyclization and subsequent transmethylation. It is postulated that this diversity of effects of 1-dodecylimidazole results from binding of the inhibitor to sterol carrier protein(s).
Pharmacokinetics of Intravenous Amoxicillin in Pediatric Patients
Authors: Rudoy Raul C. , Goto Norma , Pettit Diane , Uemura Herbert
Published: June 2012

Pharmacokinetic parameters were obtained from 14 infants and children receiving intravenous amoxicillin. Peak serum values increased proportionally to the increase in dose; the serum half-life was similar in the three dose groups studied.
Pharmacokinetics of Bay k 4999, a New Broad-Spectrum Penicillin
Authors: Wise R. , Cadge B. , Gillett A. P. , Bhamjee A. , Livingston R. , Welling P. G. , Thornhill D. P.
Published: June 2012

The pharmacokinetics of the broad-spectrum penicillin Bay k 4999 were studied in six healthy male volunteers. A 2-g dose was given by the intravenous route. The tissue penetration of the antibiotic was studied by both dermabrasion and blister techniques. A total of 26.4% of the drug was recovered in the urine in 24 h, 79% of this being excreted in the first 2 h. The elimination half-life in serum was 1.3 h. The dermabrasion levels of Bay k 4999 were generally similar to those in serum, but after 1 h the blister fluid levels of antibiotic were greater than those in serum. Different drug levels obtained by blister and dermabrasion techniques may be due to the different composition of the two fluids.
Classification of Polyene Antibiotics According to Chemical Structure and Biological Effects
Authors: Kotler-Brajtburg J. , Medoff G. , Kobayashi G. S. , Boggs S. , Schlessinger D. , Pandey R. C. , Rinehart K. L.
Published: June 2012

Fourteen polyene antibiotics and six of their semisynthetic derivatives were compared for their effects on potassium (K
+
) leakage and lethality or hemolysis of either
Saccharomyces cerevisiae
or mouse erythrocytes. These polyene antibiotics fell into two groups. Group I antibiotics caused K
+
leakage and cell death or hemolysis at the same concentrations of added polyene. In this group fungistatic and fungicidal levels were indistinguishable. Group I drugs included one triene (trienin); tetraenes (pimaricin and etruscomycin); pentaenes (filipin and chainin); one hexaene (dermostatin); and one polyene antibiotic with unknown chemical structure (lymphosarcin). Group II antibiotics caused considerable K
+
leakage at low concentrations and cell death or hemolysis at high concentrations. The fungistatic levels were clearly separable from fungicidal. This group included the heptaenes (amphotericin B, candicidin, aureofungin A and B, hamycin A and B), and five of their semisynthetic derivatives (amphotericin B methyl ester,
N
-acetyl-amphotericin B, hamycin A and B methyl esters, and
N
-acetyl-candicidin). Nystatin, classified as a tetraene, and its derivative,
N
-acetyl nystatin, also were in this group.
Effectiveness of Nafcillin, Methicillin, and Cephalothin in Experimental
Staphylococcus aureus
Endocarditis
Authors: Carrizosa Jaime , Kobasa William D. , Kaye Donald
Published: June 2012

Nafcillin, methicillin, and cephalothin (40 mg/kg every 6 h) were all effective in reducing the number of
Staphylococcus aureus
in vegetations in rabbits with endocarditis. Nafcillin and methicillin reduced the number of
S. aureus
at a significantly faster rate than did cephalothin. Nafcillin and methicillin also reduced titers of the
S. aureus
more rapidly than did cephalothin in vitro, both in broth and in rabbit serum.
Mechanism and Specificity of Action of Ribavirin
Authors: Browne Michael J.
Published: June 2012

Ribavirin at a concentration of 30 μg/ml added immediately after infection completely inhibited influenza A/Port Chalmers/1/73 (H
3
N
2
) virus hemagglutinin production in infected MDCK cells. Under these conditions, host cell protein synthesis was inhibited by only 10 to 20%. Polyacrylamide gel electrophoresis of [
35
S]methionine-labeled material from virus-infected cultures confirmed that ribavirin inhibited viral but not host cell protein synthesis. In parallel experiments, actinomycin D also preferentially inhibited viral protein synthesis. The possibility that ribavirin inhibited viral protein synthesis as a result of general inhibition of ribonucleic acid synthesis was therefore examined. In uninfected cells, ribavirin at 30 μg/ml inhibited the incorporation of [
14
C]inosine or [
3
H]uridine into ribonucleic acid but stimulated the incorporation of [
3
H]guanosine. The effects noted are consistent with an inhibition of the host cell enzyme inosine 5′-monophosphate dehydrogenase. This suggestion is supported by the finding that addition of guanosine, but not inosine, to the culture medium substantially reversed the antiviral effect of ribavirin. There was no separation between the concentration of ribavirin causing inhibition of influenza A viral protein synthesis or inhibition of MDCK cell ribonucleic acid synthesis, suggesting that ribavirin is not specifically antiviral in this system but inhibits viral protein synthesis as a result of the general inhibition of ribonucleic acid synthesis.
Relationship Between Aminoglycoside-Induced Nephrotoxicity and Auditory Toxicity
Authors: Smith Craig R. , Lipsky James J. , Lietman Paul S.
Published: June 2012

We have reviewed our data from 391 patients entered into three prospective, double-blind studies of aminoglycosides and evaluated 127 cases to determine whether aminoglycoside-induced auditory toxicity and nephrotoxicity are independent events. The cases selected for evaluation included all patients treated for greater than 3 days (mean, 7.7 days) who had serial creatinine determinations and were able to cooperate with serial bedside audiograms (250 to 8,000 Hz). Patients received either gentamicin, tobramycin, or amikacin. Drug dosage was altered to keep serum levels 1 h after administration between 5 and 10 μg/ml (gentamicin or tobramycin) or 20 and 40 μg/ml (amikacin). The investigators evaluating auditory toxicity and nephrotoxicity were blind to the aminoglycoside being administered. The incidence of auditory toxicity in the nephrotoxic group (18.2%) was not significantly different from that in the nonnephrotoxic group (15.2%) (
P
= 0.75; Fisher exact test). There was no statistical difference between the nephrotoxic and auditory toxic groups in patient age, total dose of aminoglycoside, initial creatinine level, duration of therapy, or concurrent use of furosemide or cephalothin. We conclude that aminoglycoside-induced auditory toxicity and nephrotoxicity are independent events when the drug is administered for approximately 7 days and when aminoglycoside levels are maintained within a predefined range.
In Vitro Activity of Furazlocillin (Bay k 4999) Compared with Those of Mezlocillin, Piperacillin, and Standard Beta-Lactam Antibiotics
Authors: Gootz Thomas D. , Sanders Christine C. , Sanders W. Eugene
Published: June 2012

The activity of furazlocillin (Bay k 4999) was compared with those of mezlocillin, piperacillin, and standard beta-lactam antibiotics against a number of gram-positive and gram-negative organisms. These new expanded-spectrum penicillins were less active than penicillin G against most gram-positive organisms. Furazlocillin, mezlocillin, and piperacillin showed activity comparable to ampicillin and penicillin G against
Haemophilus influenzae
and penicillin-susceptible neisseriae, respectively. None of the drugs tested was effective against penicillin-resistant gonococci. The activity of furazlocillin was greater than that of mezlocillin, piperacillin, ampicillin, or carbenicillin against many
Enterobacteriaceae
. However, certain beta-lactam-resistant strains among these organisms were not highly susceptible to any of the three new penicillins. Furazlocillin was less active than piperacillin against
Pseudomonas aeruginosa
but was more active than carbenicillin or mezlocillin. Inoculum effects and discrepancies between minimal inhibitory concentrations and minimal bactericidal concentrations were observed with furazlocillin, mezlocillin, and piperacillin against several genera. The kinetics of bacterial killing by the new penicillins were often slow and incomplete over 24 h, especially in tests with
Enterobacter
and
P. aeruginosa
. Synergy was demonstrated between furazlocillin and aminoglycosides against a variety of gram-negative bacilli and
Streptococcus faecalis
.
Inhibition of Cilia Regeneration of
Tetrahymena
by Ansamitocins, New Antitumor Antibiotics
Authors: Tanida Seiichi , Higashide Eiji , Yoneda Masahiko
Published: June 2012

Ansamitocins inhibited cilia regeneration of partially deciliated
Tetrahymena pyriformis
W, and the activity depended on the acyl groups at the C3 position.
In Vitro Model Simulating the Form of Exposure of Bacteria to Antimicrobial Drugs Encountered in Infection
Authors: Al-Asadi Mohammad J. S. , Greenwood David , O'Grady Francis
Published: June 2012

A new model, which is designed to investigate the in vitro activity of antibiotics as a function of different concentration-time curves, is described. The antibiotic is allowed to diffuse through a membrane into a bacterial culture until a peak level is reached; the antibiotic is then removed by flow-assisted back diffusion. With this arrangement it is possible to expose bacteria to a changing concentration of drug while maintaining a constant volume of bacterial culture. Preliminary studies were carried out to investigate the response of a strain of
Escherichia coli
to gentamicin. The results indicate that bacteria surviving exposure to concentrations of gentamicin similar to those obtained during therapy may exhibit an increase in resistance to the antibiotic.
Mode of Action of the Azasteroid Antibiotic 15-Aza-24-Methylene-
d
-Homocholesta-8,14-Dien-3β-ol in
Ustilago maydis
Authors: Woloshuk Charles P. , Sisler Hugh D. , Dutky Samson R.
Published: June 2012

Ustilago maydis
sporidia treated with 0.1 μg of azasterol (15-aza-24-methylene-
d
-homocholesta-8,14-dien-3β-ol) per ml appeared branched and vacuolated after 6 h of incubation. Sporidial multiplication, dry weight increase, and synthesis of protein, deoxyribonucleic acid, and ribonucleic acid were only slightly or moderately inhibited during the initial 3 h of incubation. An increase of free fatty acids was observed in lipid extracts of treated sporidia after incubation for 3 h or more. Ergosterol synthesis was completely inhibited within 1 h and there was a gradual decline of ergosterol content during 6 h which was accompanied by an accumulation of the sterol intermediate ergosta-8,14-dien-3β-ol. The results indicate that toxicity of the azasterol results from specific inhibition of the reduction of the sterol C-14(15) double bond. A triarimol-tolerant strain of
Cladosporium cucumerinum
was tolerant to the azasterol, but an imazalil-tolerant strain of
Aspergillus nidulans
was not.
Human Pharmacology of Cefotaxime (HR 756), a New Cephalosporin
Authors: Lüthy Ruedi , Münch Reiner , Blaser Jürg , Bhend Hansjörg , Siegenthaler Walter
Published: June 2012

Cefotaxime (HR 756) is a new semisynthetic parenteral cephalosporin with exceptional activity against gram-negative organisms and considerable stability against their β-lactamases. To study its pharmacokinetic properties, 0.5-, 1-, and 2-g doses were administered to each of six volunteers intravenously over 15 min, followed by a sustaining infusions of 0.5, 1, and 2 g/h, respectively, for 3 consecutive hours. The loading doses produced mean peak levels of 41, 93, and 160 μg/ml, and mean steady-state serum concentrations were 27, 64, and 138 μg/ml, respectively. The mean terminal half-life was 75 ± 7 min. The total volume of distribution averaged 0.22 ± 0.03 liters/kg of body weight. Total body and renal clearances were 232 ± 30 and 145 ± 24 ml/min per 1.73 m
2
, respectively; 63 ± 9% of the administered dose was excreted through the kidneys in 24 h. To determine the effect of cefotaxime on the renal tubules, urinary alanine aminopeptidase excretion was measured before, during, and after the infusions. It remained within the normal range in all instances; however, 48 ± 14% of the total daily alanine aminopeptidase output was recovered during the infusion period. Side effects were dose related and included fatigue, loose stools, and night sweats. No significant changes in hematology, serum chemistry, or urinalysis were recorded.
Oxacillin-Induced Lysis of
Staphylococcus aureus
Authors: Raynor Robert H. , Scott David F. , Best Gary K.
Published: June 2012

Six clinical isolates of
Staphylococcus aureus
were compared for their relative susceptibilities to the killing effects of oxacillin. Three of the strains had minimum bactericidal concentrations which were >10 times the minimum bacteriostatic concentration for this antibiotic and were designated tolerant (Tol
+
). The other strains had minimum bactericidal concentrations which were comparable to the minimum bacteriostatic concentration (Tol
−
). Lysis curves of these strains revealed that the Tol
+
strains exhibited a diminished rate of lysis when inhibited by oxacillin. This reduced rate of lysis was reflected also in a reduced rate of viability loss when the cells were exposed to oxacillin. During log growth the uptake of [
14
C]glycerol by Tol
+
cells was 1.5-fold greater than that by Tol
−
cells. Glycerol-labeled cells of each phenotype secreted radioactivity when inhibited by oxacillin. However, the Tol
+
strains released over twice as much label as the Tol
−
strains. No difference in the proportion of lipid secreted by the two phenotypes was found. The behavior of 60 to 65% of the labeled material released by inhibited cells during both sodium dodecyl sulfate gel electrophoresis and Sepharose 6B chromatography corresponded to that of lipoteichoic acid. When the major component of secreted material was added to oxacillin-inhibited Tol
−
strains, an inhibition of the lytic response was observed. These results suggest that oxacillin tolerance in
S. aureus
could be related to the enhanced secretion of an autolysin inhibitor, such as lipoteichoic acid.
Treatment of Bacterial Meningitis with Intravenous Amoxicillin
Authors: Nolan Charles M. , Chalhub Elias G. , Nash Donna G. , Yamauchi Terry
Published: June 2012

Eleven children with bacterial meningitis were treated intravenously with amoxicillin sodium to evaluate the efficacy of the parenteral form of amoxicillin for this serious infection and to measure the penetration of the drug into cerebrospinal fluid (CSF). The infecting organisms were
Haemophilus influenzae
in nine cases and
Streptococcus pneumoniae
in two. Nine patients had optimal responses to amoxicillin sodium, 200 mg/kg per day for 14 days. Bacteria were also eradicated from CSF of the other two, but one experienced fever and culture-negative CSF pleocytosis after cessation of amoxicillin, and the other developed
H. influenzae
empyema 2 weeks after termination of therapy. By comparison, 7 of 10 children with meningitis responded optimally to ampicillin (nonrandomized design) during the period of study. The mean peak CSF concentration of amoxicillin was 3.14 μg/ml (ca. 7% of the concomitant mean peak serum level) early during therapy. However, meningeal penetration of the drug declined to a mean peak of 0.63 μg/ml on the final day of therapy. Mild transient neutropenia, noted in five patients, was the most common side effect of amoxicillin sodium therapy; five patients treated with ampicillin also experienced reversible neutropenia. Thus, intravenous amoxicillin sodium provided therapy for bacterial meningitis comparable to that of ampicillin in this limited case-control study.
In Vitro Susceptibilities of
Naegleria fowleri
Strain HB-1 to Selected Antimicrobial Agents, Singly and in Combination
Authors: Lee Kenneth K. , Karr Stephen L. , Wong Ming M. , Hoeprich Paul D.
Published: June 2012

The overall prognosis of primary amoebic meningoencephalitis remains poor. The results of this study support previous finding that amphotericin B is the most efficacious drug against the
Naegleria
species in in vitro testing. In addition, the methyl ester of amphotericin B, a new derivative, also appears to be an effective agent. Of the drug combinations studied, amphotericin B plus minocycline and amphotericin B plus tetracycline showed synergy. The clinical significance of these findings remains to be determined.
Activity of β-Lactam Antibiotics Against
Pseudomonas aeruginosa
Carrying R Plasmids Determining Different β-Lactamases
Authors: Jacoby George A. , Sutton Lorraine
Published: June 2012

Azlocillin, carbenicillin, cefsulodin, mezlocillin, nocardicin A, piperacillin, pirbenicillin, sulbenicillin, and ticarcillin, but not HR756, showed reduced activity against
Pseudomonas aeruginosa
strains producing seven types of β-lactamase.
Experimental endocarditis: prophylaxis of Candida albicans infections by 5-fluorocytosine in rabbits
Authors: Demierre G , Freedman L R
Published: June 2012

The prevention of Candida endocarditis in the rabbit was easily accomplished with a single intramuscular injection of 75 mg of 5-FC (A predominantly fungistatic agent) per kg either 40 min before, or at the same time as, the intravenous challenge with Candida albicans. Renal infarcts were observed more often in rabbits with infected valvular vegetations than in control rabbits with sterile endocarditis. The prophylactic effect of 5-FC is greater in aortic vegetations than in the kidneys. This may be related to differences in the pathophysiology of infection and the pharmacokinetics of 5-FC in the two areas.
Sanguicin, a bacteriocin of oral Streptococcus sanguis
Authors: Fujimura S , Nakamura T
Published: June 2012

Streptococcus sanguis strain N-2 was found to produce a bacteriocin (sanguicin) which accumulates intracellularly. It was purified by sequential procedures about 98-fold with a recovery of 37% and appeared to be homogeneous on gel electrophoresis. Sanguicin was heat labile and was destroyed by digestion with pronase. The growth of several species of oral indigenous microorganisms was inhibited by sanguicin, of which Bacteriodes melaninogenicus was most susceptible. Sanguicin acted on susceptible cells as a bacteriostatic agent.
RMI 15,731 (1-[5-tetradecyloxy-2-furanyl]-ethanone), a new antirhinovirus compound
Authors: Ash R J , Parker R A , Hagan A C , Mayer G D
Published: June 2012

RMI 15,731 (1-[5-tetradecyloxy-2-furanyl]-ethanone) is a new antiviral compound with activity specific for rhinoviruses. Virus synthesis in R-HeLa cells was susceptible to low concentrations (0.25 micrograms/ml) of the compound. RMI 15,731 was effective if added for 1 h before infection and removed or if added as late as 6 h postinfection. Low concentrations of the compound directly inactivated infectious rhinovirus in a time- and temperature-dependent fashion. RMI 15,731 appears to be a promising new antirhinovirus compound for clinical evaluation since it (i) blocks intracellular virus synthesis (without cellular toxicity), and (ii) directly inactivates virions. The last property may be important in limiting virus shedding from an infected host.
Clinicopharmacological evaluation of amoxicillin and probenecid against bacterial meningitis
Authors: Craft J C , Feldman W E , Nelson J D
Published: June 2012

Forty-three infants and children with bacterial meningitis were treated intravenously with 200 mg of amoxicillin sodium per kg per day for 10 days. (Patients were initially treated with ampicillin and chloramphenicol until the bacterial etiology was defined.) Patients were randomly treated with amoxicillin only or with amoxicillin and four doses of probenecid (10 mg/kg per dose) orally every 6 h for 24 h before the lumbar puncture at day 10. Serum and cerebrospinal fluid (CSF) were obtained on days 1, 5, and 10 of therapy for antibiotic assay. The mean peak serum concentration of amoxicillin of 49.2 micrograms/ml was increased to 61.4 micrograms/ml in patients who received probenecid. The half-life in serum (1.5 h) and area under the curve with probenecid (112.5 micrograms/ml-h) were increased compared with those of amoxicillin alone (1.3 h and 82.2 micrograms/ml-h). The mean peak CSF concentrations on days 1 and 5 were similar, but day 1 concentrations remained between 2.0 micrograms/ml and 5.0 micrograms/ml throughout the 4 h after a dose, whereas the day 5 values decreased at the same decay rate as that in serum. All CSF concentrations were lower on day 10, but patients receiving probenecid had peak values occurring at 1 hr rather than at 0.5 h, and levels were significantly greater at 1 and 2 h after a dose. There were no deaths and patients responded well to treatment.
Mechanism of synergistic action of a combination of ampicillin and dicloxacillin against a beta-lactamase-producing strain of Citrobacter freundii
Authors: Mizoguchi J , Suginaka H , Kotani S
Published: June 2012

The mechanism of synergistic activity of a combination of ampicillin and dicloxacillin was studied on beta-lactamase-producing Citrobacter freundii GN346 and its derived beta-lactamaseless mutant GN346/16. The synergistic activity was exhibited against the parent strain but not against the mutant strain. Precultivation of the parent strain with the combination reduced the amount of the subsequent binding of [14C]penicillin G to the membrane fraction from the treated cells, but no reduction was observed in the case of cells treated with ampicillin or dicloxacillin alone. On the other hand, the amount of binding of [14C]penicillin G to the membrane fraction from the mutant strain was reduced by ampicillin treatment alone. These results clearly indicated that dicloxacillin inhibited the beta-lactamase activity produced by the parent strain, and, consequently, ampicillin can penetrate through the outer membrane and periplasmic beta-lactamase barrier into its target sites on the cytoplasmic membrane.
Lipid composition and sensitivity of Prototheca wickerhamii to membrane-active antimicrobial agents
Authors: Sud I J , Feingold D S
Published: June 2012

The lipid composition of Prototheca wickerhamii ATCC 16529 is presented and discussed in relation to the unique susceptibility of the organism to drugs of three membrane-active antimicrobial classes: the polyenes, the polymyxins, and the imidazoles. The presence of ergosterol in the neutral lipid fraction of the membrane is likely responsible for the exquisite susceptibility to amphotericin B. The presence of a large quantity of free fatty acids in the membrane appears responsible for imidazole susceptibility. The membrane determinants of polymyxin B susceptibility are less well defined.
Assay of flucytosine (5-fluorocytosine) in human plasma by high-pressure liquid chromatography
Authors: Bury R W , Mashford M L , Miles H M
Published: June 2012

The use of the antifungal agent flucytosine has been associated with dose-related hepatotoxicity and bone marrow depression, and measurement of plasma concentrations is useful in determining dosage schedules. The present study describes a rapid, simple, and sensitive high-pressure liquid chromatographic analysis of plasma flucytosine which may be completed within 30 min of receipt of a plasma sample. Sample preparation is minimal and merely involves precipitation of plasma protein before injection onto a reverse-phase column. The method is accurate and reproducible and yields results comparable to or perhaps slightly superior to those obtained by conventional microbiological assay. The value of the procedure for routine use is enhanced by the freedom from interference by a large range of medications administered concurrently with flucytosine.
Affinities of penicillins and cephalosporins for the penicillin-binding proteins of Escherichia coli K-12 and their antibacterial activity
Authors: Curtis N A , Orr D , Ross G W , Boulton M G
Published: June 2012

The affinities of a range of penicillins and cephalosporins for ther penicillin-binding proteins of Escherichia coli K-12 have been studied, and the results were compared with the antibacterial activity of the compounds against E. coli K-12 and an isogenic permeability mutant. Different penicillins and cephalosporins exhibited different affinities for the "essential" penicillin-binding proteins of E. coli K-12, in a manner which directly correlated with their observed effects upon bacterial morphology. Furthermore, the affinities of the compounds for their "primary" lethal penicillin-binding protein targets showed close agreement with their antibacterial activities against the permeability mutant.
Agar disk diffusion susceptibility characteristics of azlocillin, carbenicillin, mezlocillin, piperacillin, and ticarcillin
Authors: Phaneuf D , Neu H C
Published: June 2012

The agar disk diffusion susceptibility of Enterobacteriaceae to mezlocillin and piperacillin was correlated with agar minimal inhibitory concentrations and compared with the susceptibility to carbenicillin. The agar disk susceptibility of Pseudomonas aeruginosa to azlocillin, mezlocillin, and piperacillin was correlated with agar minimal inhibitory concentrations and compared with the susceptibility to carbenicillin and ticarcillin. Criteria are offered for the zones of inhibition to provide information about resistant and susceptible isolates that correlate with known serum levels.
Amantadine aerosols in normal volunteers: pharmacology and safety testing
Authors: Hayden F G , Hall W J , Douglas R G , Speers D M
Published: June 2012

The acceptability and pharmacology of intermittent aerosol administration of amantadine was assessed in healthy volunteers. Amantadine solutions of 2.5, 1.5, or 1.0 g/100 ml were used for 12 30-min, twice-daily aerosol treatments in 15 subjects. Overall, the aerosol treatments were well tolerated. During and up to 1 h after aerosol exposures, nasal irritation, rhinorrhea, dysgeusia, or a combination of symptoms was experienced by some of the subjects receiving either of the two higher amantadine concentrations. Aerosol treatments were associated with small but statistically significant decreases in maximal expiratory flow rates. One hour after aerosol treatments with the 1.0-g/100 ml solution, amantadine levels in nasal wash samples (mean, 30.3 micrograms/ml; range, 1.7 to 108 micrograms/ml) greatly exceeded blood and nasal wash levels reported after oral administration. Amantadine can be administered safely by small-particle aerosol to humans in doses that could be expected to exert an antiviral effect in influenza A virus infections.
In vitro activity of three tetracycline antibiotics against Acinetobacter calcoaceticus subsp. anitratus
Authors: Crues J V , Murray B E , Moellering R C
Published: June 2012

The in vitro activity of three tetracycline antibiotics against 127 strains of Acinetobacter calcoaceticus (Herella vaginicola) were compared. Almost all strains were susceptible to minocycline and doxycycline, whereas most strains were resistant to tetracycline.
Rifampin plus trimethoprim: bactericidal activity and suppression of resistance in human urine in vitro
Authors: Goldstein B P , Ripamonti I F , Bolzoni G , Carniti G , Arioli V
Published: June 2012

The bactericidal effect of a combination of rifampin (Ramp) and trimethoprim (Tmp) was studied using dense cultures of test organisms, including some urinary pathogens, growing in human urine. Drug concentrations used were similar to those attainable in human urine. The combination was more effective than the individual drugs and than a combination of Tmp plus sulfamethoxazole (Smx). Tmp was bactericidal in urine and blocked the emergence of Ramp-resistant bacteria. Ramp was responsible for most of the bactericidal action of the combination but also potentiated the bactericidal activity of Tmp. Ramp suppressed the selection of thy- (Tmp-resistant) bacteria. Under the experimental conditions, Smx+Tmp was not more bactericidal than Tmp alone for most of the test organisms, despite strong synergy between the two at subinhibitory concentrations.
Comparison of activity and beta-lactamase stability of cefotaxime with those of six other cephalosporins
Authors: Mouton R P , Bongaerts G P , van Gestel M
Published: June 2012

A study of the susceptibility to cefotaxime and six other cephalosporins in 213 nonselected strains of nine different bacterial species clearly showed that cefotaxime was the most active against aerobic gram-negative bacilli. The same pattern emerged with 84 cephalothin-resistant strains of five enterobacterial species, but the mean minimal inhibitory concentration values for all cephalosporins were about twofold higher in this group of strains. Cephalothin was the most active antibiotic against Staphylococcus aureus. The inoculus effect of 10 cephalothin-resistant strains was relatively small, but it was most marked for cefamandole, as compared with that of three other new cephalosporins, including cefotaxime. The susceptibility of these cephalosporins to beta-lactamases from 12 beta-lactamase-producing enterobacterial strains was determined. Half of these were slightly active against cefotaxime and had similar activity against cefuroxime. Cefoxitin was not degraded at all, and cefamandole was the most susceptible. No correlation between beta-lactamase susceptibility and minimal inhibitory concentration values of different cephalosporins was found. Cefotaxime combined high intrinsic antibiotic activity with marked resistance to beta-lactamase inactivation.
Bactericidal effect of combinations of antimicrobial drugs and antineoplastic antibiotics against gram-negative bacilli
Authors: Michel J , Jacobs J Y , Sacks T
Published: June 2012

Six antineoplastic antibiotics showed little antibacterial activity against 28 strains of four species of gram-negative enteric bacteria. By using the cellophane transfer technique, combinations of these agents with 16 antibacterial drugs usually showed indifference. However, combinations of mitomycin C, especially with the aminoglycosides, were synergistic on strains of Escherichia coli, Proteus, and Klebsiella pneumoniae. Bleomycin, on the other hand, often showed antagonism on strains of E. coli and K. pneumoniae with the beta-lactams, aminoglycosides, and other antibacterial agents. Checkerboard titrations and kinetic killing curves confirmed these findings.
Butirosin, a New Aminoglycosidic Antibiotic Complex: Bacterial Origin and Some Microbiological Studies
Authors: Howells John D. , Anderson Lucia E. , Coffey George L. , Senos Georgia D. , Underhill Marjorie A. , Vogler Dorothy L. , Ehrlich John
Published: June 2012

Butirosin, a new aminoglycosidic antibiotic complex, was produced by submerged fermentation with each of two strains of
Bacillus circulans
. A paper-disc, agar-diffusion assay which employs
Escherichia coli
(P-D 04863) as the test organism has been developed. Shaken-flask and stirred-jar fermentations in a medium containing glycerol, soybean meal, meat peptone, ammonium chloride, and calcium carbonate reach titers of 500 to 700 μg of butirosin base per ml. Butirosin is active against several gram-positive and gram-negative bacteria including
Pseudomonas aeruginosa
.
Cross-Resistance and Collateral Susceptibility to Antifolic Antimalarial Compounds
Authors: Smith Carl C. , Genther Clara S.
Published: June 2012

Series of strains of
Streptococcus faecium
ATCC 8043,
Lactobacillus casei
ATCC 7469, and
Pediococcus cerevisiae
ATCC 8081 with increasing resistance to the active antifolate antimalarial drugs chlorguanide triazine (CGT), pyrimethamine (PM), and trimethoprim (TMP) were isolated. These mutant strains, stable for at least 3 to 5 years, were examined for cross-resistance and collateral susceptibility to the above compounds and to methotrexate (MTX). Generally, they exhibited cross-resistance to all four compounds, but resistance of a strain to one compound did not predict accurately its resistance to another drug. Unexpectedly,
L. casei
resistant to CGT exhibited collateral susceptibility to MTX, TMP, and PM varying from 5- to 20-fold.
P. cerevisiae
developed resistance to CGT readily but maintained its susceptibility to PM and TMP after prolonged exposure to these compounds. Resistance to these antimalarial antifolates was accompanied by only low-grade cross-resistance to MTX, a representative antileukemic antifolate agent.
In Vitro Studies of Tobramycin
Authors: Bodey Gerald P. , Stewart Dorothy
Published: June 2012

The in vitro activity of tobramycin was studied against 457 clinical isolates of gram-negative bacilli and 151 clinical isolates of gram-positive cocci. The vast majority of the gram-negative bacilli was inhibited by tobramycin at a concentration of 1.56 μg or less per ml. Only a few isolates of
Staphylococcus aureus
and no isolates of
Streptococcus pyogenes
or
Diplococcus pneumoniae
were susceptible to this drug. Tobramycin was generally more active than gentamicin sulfate against gram-negative bacilli, although organisms resistant to gentamicin sulfate were also resistant to tobramycin. The major difference between the two drugs was the greater activity of tobramycin against
Pseudomonas aeruginosa
.
Treatment of Experimental Staphylococcal Infection with Rifampin
Authors: Lobo Monica C. , Mandell Gerald L.
Published: June 2012

Bacteria surviving within leukocytes are protected from the lethal action of high concentrations of most antibiotics, which may explain, in part, the failure of bactericidal antibiotics to eradicate staphylococci from abscesses. Since rifampin is unique in its ability to kill intraleukocytic bacteria, the efficacy of this drug was tested in the treatment of staphylococcal infections in mice. Groups of mice infected intravenously with
Staphylococcus aureus
were treated with rifampin (20 mg/kg), procaine penicillin (937.5 mg/kg), or methicillin (200 mg/kg). All untreated mice died with disseminated visceral abscesses. After 10 days of therapy, survival in groups treated with penicillin and methicillin was 16 and 20%, respectively, whereas with rifampin it was 80% (
P
< 0.0005). Antibiotic concentrations in the serum of mice treated with penicillin, methicillin, or rifampin were bactericidal for the strain of
S. aureus
used. Serial bacterial counts of kidney, lung, and spleen homogenates showed that neither penicillin nor methicillin was able to eradicate staphylococci, whereas rifampin completely sterilized those organs in many mice. When abscess contents and infected peritoneal washings were incubated with high concentrations of penicillin, methicillin, or rifampin, only rifampin killed all of the bacteria. The capacity of rifampin to eradicate staphylococci from pus in vitro and from abscesses in mice appears to be related to the ability of rifampin to kill intraleukocytic bacteria.
Cephamycins, a New Family of β-Lactam Antibiotics. IV. In Vivo Studies
Authors: Miller A. Kathrine , Celozzi Evemarie , Kong Yulin , Pelak Barbara A. , Kropp Helmut , Stapley Edward O. , Hendlin David
Published: June 2012

Cephamycin A was found to be more active in vivo than cephamycin B. In comparison with cephamycin C, cephamycin A was more active against gram-positive organisms but less active against gram-negative organisms. Given subcutaneously, cephamycin C had good in vivo gram-negative activity, comparing favorably with cephalothin and cephaloridine against cephalosporin-susceptible organisms. In general, against the gram-negative organisms, it was more active than cephalothin or cephalosporin C and about as active as cephaloridine. In addition, cephamycin C protected mice against β-lactamase-producing
Proteus
cultures, including clinically isolated strains. The compound is remarkably nontoxic. Cephamycin C was detected in the serum and recovered from the urine of treated mice to about the same extent as cephaloridine. Like cephaloridine and cephalosporin C, cephamycin C must be excreted mainly by glomerular filtration, because the use of probenecid did not enhance the therapeutic effectiveness nor concentrations of these agents in the sera of treated mice.