bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of Ribavirin on BHK-21 Cells Acutely or Persistently Infected With Mumps Virus
Authors: McCammon James R. , Riesser Valerie W.
Published: June 2012

The effects of ribavirin on BHK-21 cells acutely infected with mumps virus were compared to the effects of the drug on the same cell line persistently infected with mumps virus. Visible cytotoxicity was minimal for both cell types; however, there was an inhibition of cell replication with increasing drug concentrations. Ribavirin had marked antiviral activity against both the acute and persistent infections as determined by an inhibition of hemadsorption plaque formation, decreased immunofluorescence, and a reduction in the release of infectious virus. Even after the drug had been on the persistently infected cells for 72 h, there was still antigen production detectable by immunofluorescence, although the cells no longer hemadsorbed chicken erythrocytes. Ribavirin removal from both types of infection resulted in the renewed synthesis of virus.
Quantitative Nasal Cultures from Carriers of
Staphylococcus aureus
: Effects of Oral Therapy with Erythromycin, Rosamicin, and Placebo
Authors: Wilson Samuel Z. , Martin R. Russell , Putman Margaret , Greenberg Stephen B. , Wallace Richard J. , Jemsek Joseph G.
Published: June 2012

Serial quantitative nasal cultures were performed on 87 healthy nasal carriers of
Staphylococcus aureus
, who were randomly assigned to 7 days of oral therapy with erythromycin, rosamicin (an investigational macrolide antibiotic), or placebo. Staphylococcal carrier rates decreased during therapy with both antibiotics; however, erythromycin was significantly more effective in lowering carrier rates than was rosamicin. The anti-staphylococcal effects of both antibiotics were similar when the mean numbers of
S. aureus
isolated from positive cultures during therapy were compared. Side effects to each regimen were minimal.
Antibiotic Action of
N
-Methylthioformohydroxamate Metal Complexes
Authors: Bell Stuart J. , Friedman Stanley A. , Leong John
Published: June 2012

The antibiotic activity of metal complexes of
N
-methylthioformohydroxamic acid against gram-negative
Escherichia coli
NIHJ and gram-positive
Staphylococcus aureus
209P was investigated. The kinetically labile, square-planar, divalent (Cu, Ni, and Pd) and octahedral, trivalent (Fe, Co, and Cr) complexes displayed activity, whereas the more inert platinum(II) or rhodium(III) complex displayed no activity, or activity only at elevated concentrations. The free ligand did not suppress the growth of the above organisms, and the sulfur atom of the ligand in its metal complexes appears crucial for activity. Uptake studies of radioactively labeled
N
-methylthioformohydroxamic acid, its nickel(II), platinum(II), iron(III), and rhodium(III) complexes were conducted in the
Escherichia coli
K-12 RW193 mutant, which is defective in the production of its native iron(III) transport agent, enterobactin. Uptake of
55
Fe or
63
Ni label from their metal complexes appeared to occur as free inorganic metal ions. The antibiotic activity of the iron(III) and nickel(II) complexes was not due merely to an enhanced accumulation of metal ions by the cell. Metal complexes of [
35
S]
N
-methylthioformohydroxamic acid enhanced the accumulation of
35
S label compared to that of the free ligand. The antibiotic activity and uptake data are discussed in terms of possible modes of action.
In Vitro Activity and β-Lactamase Stability of Cefazaflur Compared with Those of β-Lactamase-Stable Cephalosporins
Authors: Aswapokee Nalinee , Neu Harold C.
Published: June 2012

The in vitro activity of cefazaflur, a parenteral cephalosporin, was determined against 590 clinical isolates. Cefazaflur inhibited the majority of gram-positive cocci at concentrations below 1 μg/ml except for enterococci. The agent was as active as cefamandole or cefoxitin against most
Escherichia coli, Klebsiella pneumoniae
, and
Proteus mirabilis
. Although it inhibited a number of strains of
Enterobacter
, indole-positive
Proteus
, and
Serratia
resistant to cephalothin, it was much less active against these organisms than were cefamandole or cefoxitin.
Resistance Mechanisms of Multiply Resistant Pneumococci: Antibiotic Degradation Studies
Authors: Robins-Brown R. M. , Gaspar M. N. , Ward J. I. , Wachsmuth I. K. , Koornhof H. J. , Jacobs M. R. , Thornsberry C.
Published: June 2012

Strains of
Streptococcus pneumoniae
resistant to penicillin have been reported from several countries around the world. Many South African isolates, in addition, exhibit resistance to tetracycline, chloramphenicol, erythromycin, clindamycin, and cotrimoxazole in varying patterns. A qualitative test of the ability of antibiotic-resistant pneumococci to inactivate penicillin, oxacillin, cephalothin, cefoxitin, chloramphenicol, tetracycline, minocycline, erythromycin, clindamycin, streptomycin, gentamicin, and cotrimoxazole revealed that only chloramphenicol was degraded. This finding was confirmed in a quantitative test in which the residual antimicrobial activity of broth containing chloramphenicol in subinhibitory concentrations was determined after incubation with antibiotic-resistant bacteria. Chloramphenicol resistance was shown to be associated with the production of inducible chloramphenicol acetyltransferase. No beta-lactamase activity was demonstrated. Plasmid deoxyribonucleic acid was not demonstrable in partially purified lysates of antibiotic-resistant strains of
S. pneumoniae
.
Dissociated Resistance Among Cephalosporins
Authors: Waterworth Pamela M. , Emmerson A. M.
Published: June 2012

When disks containing cefuroxime (CXM) or HR 756 (756) were placed next to cefoxitin (FOX) on plates inoculated with
Enterobacter
resistant to FOX, there was marked flattening of the zones of inhibition produced by CXM or 756, but colonies growing near the CXM or 756 disks were found to be fully susceptible to these drugs on retesting. In contrast, when a checkerboard titration with CXM or 756 and FOX was done in broth, organisms growing in the presence of high concentrations of either of the former plus FOX were found to be resistant on retesting. Broth cultures of
Enterobacter
were found to contain small numbers of mutants which were resistant to and inactivated CXM and 756. Evidence is presented suggesting that the addition of FOX induces similar properties in the whole culture, which then becomes resistant to all of the nine cephalosporins tested and to four of six penicillins tested. Such cultures rapidly reverted to susceptible when FOX was removed or inactivated, and an explanation is offered as to why this did not happen in fluid media.
Purification, Properties, and Cytotoxic Effect of a Bacteriocin from
Mycobacterium smegmatis
Authors: Saito Hajime , Watanabe Takashi , Tomioka Haruaki
Published: June 2012

The bacteriocin produced by
Mycobacterium smegmatis
ATCC 14468 was isolated, and a study was made of its chemical, physical, and biological properties. No appreciable bacteriocin activity was found in the culture supernatant fluids, but it was released in appreciable quantities after disruption of the cells. The material was purified 49-fold by means of chromatography on diethylaminoethyl-cellulose, ammonium sulfate fractionation, gel filtration on Sephadex G-200, and chromatography on diethylaminoethyl-Sephadex A-50. Its molecular weight was determined to be approximately 75,000 from the elution profile on Sephadex G-200 chromatography. The bacteriocin was resistant to deoxyribonuclease, ribonuclease, lipase, ultraviolet irradiation, and freeze-thawing, whereas it was relatively less thermostable and was sensitive to proteolytic enzymes. The lethal effect of the bacteriocin was demonstrated by the decrease in viable counts of the bacteriocin-sensitive indicator strain,
M. diernhoferi
ATCC 19340. The bacteriocin preparation inhibited the growth of HeLa-S3 cells.
Effect of Acycloguanosine Treatment on Acute and Latent Herpes Simplex Infections in Mice
Authors: Field Hugh J. , Bell Susanne E. , Elion Gertrude B. , Nash Anthony A. , Wildy Peter
Published: June 2012

Systemic treatment of mice with the nucleoside analog 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine [aciclovir]) was found to be highly effective against acute type 1 herpes simplex virus infection of the pinna. The drug ablated clinical signs and reduced virus replication both in tissue local to the inoculation site and within the nervous system. Provided that moderate-sized virus inocula were used, acycloguanosine treatment reduced or prevented the establishment of a latent infection in the dorsal root ganglia relating to the sensory nerve supply of the ear. However, although it aborted artificially produced infections in dorsal root ganglia, acycloguanosine was found not to be effective against the latent infection once established. This finding strongly indicated that latent herpes simplex virus in mice can exist in a nonreplicating form.
Relationship Between Serum and Saliva Chloramphenicol Concentrations
Authors: Koup Jeffrey R. , Lau Alan H. , Brodsky Barbara , Slaughter Richard L.
Published: June 2012

The relationship between serum and saliva chloramphenicol (CAP) concentrations was evaluated in 27 paired specimens collected from 20 hospitalized patients during therapy with the drug. A significant (R = 0.80,
P
< 0.001) but variable relationship was found to exist. Serum protein binding of CAP was also evaluated (43.7 ± 5.7% bound;
N
= 24). Differences in CAP binding did not apparently account for a significant portion of the variability in the observed saliva/serum CAP concentration ratios. The degree of variation observed indicated that saliva CAP concentrations could not be relied upon for the prediction of serum CAP concentrations.
Effect of Cephalothin on Measurement of Creatinine Concentration
Authors: Rankin Laura I. , Swain Richard R. , Luft Friedrich C.
Published: June 2012

Cephalothin, an antibiotic implicated as nephrotoxic, falsely elevates the creatinine concentration as determined by the Jaffé reaction in vitro. We studied this effect in vivo and demonstrated variable degrees of interference in determinations of plasma and urinary creatinine concentrations by two automated methods. Clinicians should be aware of this phenomenon in patients receiving cephalothin, both when monitoring renal function and when assessing patient reliability in the collection of timed urine specimens.
Latent Herpes Simplex Virus Infections in Sensory Ganglia of Hairless Mice Prevented by Acycloguanosine
Authors: Klein Richard J. , Friedman-Kien Alvin E. , DeStefano Eugene
Published: June 2012

Acycloguanosine (ACG) was able to prevent the fatal outcome of herpes simplex virus-induced skin infections of the lumbosacral or orofacila area in hairless mice. Topical ACG treatment was more effective than systemic treatment in preventing the evolution of skin lesions. Acute ganglionic infections in the trigeminal ganglia were prevented by ACG, and latent ganglionic infections did not become established when the ACG treatment was initiated 3 h after infection. Serum antibody titers were, on the average, eight times higher in mice which developed latent ganglionic infections after ACG treatment than in mice without evidence of herpes simplex virus latency in ganglia. Reinoculation of ACG-treated mice at a site different from that of the primary inoculation did not lead to the establishment of a second latent infection with the homologous virus type when a latent infection was already present. In mice without evidence of latent infection after the primary inoculation, a latent infection at the site of reinoculation became established in 25% of the animals.
Penetrability of the Outer Membrane of
Neisseria gonorrhoeae
in Relation to Acquired Resistance to Penicillin and Other Antibiotics
Authors: Scudamore R. Allan , Beveridge Terrance J. , Goldner Morris
Published: June 2012

Acquired antibiotic resistance in
Neisseria gonorrhoeae
is principally associated with three genetic markers,
penA, mtr
, and
penB. penA
is a specific marker for penicillin resistance, whereas
mtr
and
penB
are nonspecific in conferring resistance to penicillin and several other antibiotics as well. It has been suggested that the nonspecific markers may cause a general decrease in the penetrability of the gonococcal outer membrane. To investigate this, antibiotic penetration of the outer membrane was studied in two isogenic strains—FA19 (susceptible parent) and FA140 (containing
penA, mtr
, and
penB
)—and also in a clinical isolate with multiple resistance. The method involved brief treatment of exponential cells with ethylenediaminetetraacetic acid at 5°C to disrupt the outer membrane barrier. The 50% inhibitory concentrations of antibiotics for treated and normal cells were measured turbidimetrically, and from their ratios outer membrane penetration barriers were calculated. Small barriers were observed for actinomycin D and benzylpenicillin, and these were very similar in the susceptible and resistant strains. Also, in FA140 no significant barriers for rifampin, erythromycin, and tetracycline were detected. These results suggest that mechanism(s) other than reduced outer membrane penetrability underlie acquired resistance due to
penA, mtr
, and
penB
.
Pharmacokinetics of Cephradine Suspension in Infants and Children
Authors: Ginsburg Charles M. , McCracken George H.
Published: June 2012

The pharmacokinetics of cephradine suspension were studied in 16 infants and children who were 13 months to 8 years and 3 months of age (means age, 3.5 years). Mean peak concentrations of 21.3 and 9.9 μg/ml were achieved at 30 min after administration of 60-mg/kg doses to fasting and nonfasting patients. The area under the serum concentration-time curve was 26% larger in fasting than in fed subjects. The half-life of cephradine in serum was 0.8 and 1.0 h in fasting and fed groups, respectively. Antimicrobial activity was detected in 49% of all salivary samples; in 75% of specimens, the concentrations were less than the 50% minimum inhibitory concentration for most pneumococci and group A streptococci. Urinary concentrations of cephradine ranged from 28 to 8,760 μg/ml and were independent of feeding status.
Spectrophotometric Assay for Amikacin Using Purified Kanamycin Acetyltransferase
Authors: Scarbrough Emanual , Williams Jeffrey W. , Northrop Dexter B.
Published: June 2012

A rapid spectrophotometric assay has been developed for measuring the concentrations of amikacin and related antibiotics in serum. The assay uses a purified enzyme from R-factor
E. coli
which acetylates amikacin with the production of coenzyme A, the latter in turn being reacted with a sulfhydryl reagent to produce stoichiometric amounts of a sensitive chromophore, that is measured in the visible spectrum. The system complements an earlier assay for gentamicin-related antibiotics thereby facilitating the rapid measurement of the concentrations of all clinically important aminoglycosides in serum.
In vitro activity of LY127935
Authors: Barza M , Tally F P , Jacobus N V , Gorbach S L
Published: June 2012

The activity of LY127935, a beta-lactam antibiotic of novel structure, was studied in vitro against facultative gram-negative bacilli, Staphylococcus aureus, and Bacteroides fragilis. The strains were recent clinical isolates, many of which were relatively resistant to other antibiotics. LY127935 exhibited striking activity against Escherichia coli, Klebsiella pneumoniae, Enterobacter sp., Proteus sp., Serratia marcescens, and B. fragilis with median minimum inhibitory concentrations of less than or equal to 1.0 micrograms/ml. It was somewhat less active against Pseudomonas aeruginosa and S. aureus. Cefotaxime (HR 756) showed very similar activity except that it was substantially weaker against B. fragilis. LY127935 was more active than cefamandole, cefoxitin, or piperacillin; it was also as potent as tobramycin or amikacin against all species except for P. aeruginosa.
Purification and characterization of agrocin 84
Authors: Thompson R J , Hamilton R H , Pootjes C F
Published: June 2012

A procedure for the rapid purification of milligram quantities of agrocin 84, a bacteriocin-like compound produced by Agrobacterium radiobacter strain K-84, has been developed. This procedure, which employs charcoal adsorption, ion-exchange, sieving chromatography, and continuous-flow electrophoresis, can yield agrocin 84 which is 65% pure on a dry weight basis. The purest preparations were strongly ultraviolet absorbing, with a maximum at 264 nm (epsilon 7.0/264 = 22,675 cm2 - M-1) and a minimum at 227 nm (ratio of 264 to 227 nm, 6.00). As has been reported, agrocin 84 contains an unusual phosphoramidate or 6-N-acyl linkage to adenine. Adenine, glucose, and phosphate are present in a 1:1:2 molar ratio. The molecular weight was estimated to be 1,350.
Antibiotic susceptibilities of human isolates of Pasteurella multocida
Authors: Stevens D L , Higbee J W , Oberhofer T R , Everett E D
Published: June 2012

Seventeen human strains of Pasteurella multocida, biochemically similar to, if not identical with, isolates of animal origins, were tested for susceptibility to 16 antimicrobial agents utilizing a microtiter broth dilution technique. Ten of these isolates were also tested against 11 antibiotics by disk diffusion. The most active drugs with respect to the median minimal inhibitory concentration (micrograms per milliliter) were tetracycline (0.09), penicillin G (0.78), ampicillin (0.78), carbenicillin (1.56), cephalothin (1.56), and chloramphenicol (1.56). With the exception of tetracycline, the median minimal inhibitory concentration and minimal bactericidal concentration values were equal or differed by no more than a factor of two. The semisynthetic penicillins clindamycin, erythromycin, and aminoglycosides had relatively low activities, suggesting that these agents would be poor choices for the treatment of P. multocida infections.
Netilmicin treatment of complicated urinary tract infection in patients with renal function impairment
Authors: Frimodt-Möller N , Maigaard S , Madsen P O
Published: June 2012

The efficacy and tolerance of netilmicin was studied in 28 elderly male patients with varying degrees of renal function impairment who suffered from complicated urinary tract infections. Doses of netilmicin, equivalent to 2 mg/kg divided by milligrams of creatinine per 100 ml, were administered every 12 h. A 62% cure rate, defined as negative urine culture at 1-week follow-up, was obtained. Treatment failure correlated with impaired renal function. Nephrotoxic reaction, defined as any significant increase in serum creatinine during treatment, was found in 6 of 28 patients (21%). The increase in serum creatinine was transient in all except one of these patients. Apart from the finding of a significant correlation between nephrotoxic reaction to netilmicin and postoperative urinary tract infection, no clinical or therapeutic features correlated with nephrotoxicity; trough concentrations correlated with serum creatinine.
Cinoxacin: pharmacokinetics and tolerance in patients with normal and impaired renal function
Authors: Maigaard S , Frimodt-Möller N , Welling P G , Madsen P O
Published: June 2012

The pharmacokinetics of cinoxacin, a new antibacterial compound related to nalidixic acid and oxolinic acid, were investigated in 22 patients with varying degrees of renal impairment. After oral administration of cinoxacin at 500 mg every 12 h for 7 days to all patients, the drug was found to be well tolerated. The urine concentrations of cinoxacin in all patients far exceeded the minimal inhibitory concentrations for susceptible organisms commonly found in urinary tract infections. The serum half-life of cinoxacin in patients with normal renal function was approximately 2.7 h but increased to approximately 8.5 h in patients with creatinine clearance less than 30 ml/min. No undue drug accumulation was demonstrated in any patient group during the treatment. Highly significant correlations were found between the elimination rate constant and creatinine clearance and also between the elimination half-life and serum creatinine. The bioavailability of cinoxacin was independent of renal function.
Collaborative Evaluation of a Proposed Reference Dilution Method of Susceptibility Testing of Anaerobic Bacteria
Authors: Sutter Vera L. , Barry Arthur L. , Wilkins Tracy D. , Zabransky Ronald J.
Published: June 2012

An agar dilution method for susceptibility testing of anaerobic bacteria was evaluated to determine whether results obtained would be consistent enough to recommend it as a reference method. The study was conducted in 10 laboratories where the minimum inhibitory concentrations of six antibiotics (carbenicillin, cefoxitin, chloramphenicol, clindamycin, penicillin G, and tetracycline) were determined against 10 bacterial strains on Wilkins-Chalgren agar prepared by three manufacturers. Minimum inhibitory concentrations falling on the modes varied from 57 to 80% of all determinations and on the mode or within ±1 log
2
dilution of the mode from 87 to 100% within each laboratory. When data from all laboratories were pooled, minimum inhibitory concentrations from each laboratory agreed with the overall mode 48 to 71% of the time, with an overall agreement at ±1 log
2
dilution of 96%. This degree of reproducibility allows for recommendation of the procedure as a reference method. Results with three of the test strains were very consistent, and these strains are recommended as control strains:
Clostridium perfringens
ATCC 13124,
Bacteroides fragilis
ATCC 25285 and
Bacteroides thetaiotaomicron
ATCC 29741. The minimum inhibitory concentrations for these strains were on the mode or within ±1 log
2
dilution of the mode 98, 99, and 99% of the time, respectively. The remaining anaerobic bacteria are recommended as reference strains.
Pharmacokinetics of cefotaxime
Authors: Fu K P , Aswapokee P , Ho I , Matthijssen C , Neu H C
Published: June 2012

The pharmacokinetics of cefotaxime after intramuscular injection and intravenous infusion were determined. The mean peak serum level after the 500-mg intramuscular dose was 11.7 micrograms/ml, and it was 20.5 micrograms/ml after a 1,000-mg dose. The serum half-life was 1.2 and 1.3 h, respectively for the two doses. The apparent fractional volumes of distribution of 32 and 37 liters were not significantly different for the two doses, and the fractional serum clearance was approximately 315 ml/min per 1.73 m2 for both doses. The mean peak serum level after 1,000 mg administered by intravenous infusion over 30 min was 41.1 micrograms/ml. The half-life was 1.13 h, apparent volume of distribution was 33 liters, serum clearance 341 ml/min per 1.73 m2, and renal clearance was 130 ml/min per 1.73 m2. The pharmacology of cefotaxime is similar to the pharmacology of other cephalosporin antibiotics, but the low inhibitory levels which it has against gram-positive and gram-negative bacteria suggest that lower dosage regimens should be possible.
Amikacin resistance associated with a plasmid-borne aminoglycoside phosphotransferase in Escherichia coli
Authors: Perlin M H , Lerner S A
Published: June 2012

Enzymatic phosphorylation of amikacin has not been reported previously in gram-negative bacteria. We found that extracts of MP1, a mutant of Escherichia coli JR66/W677 that is resistant to amikacin, were able to phosphorylate this aminoglycoside more rapidly than were extracts of the parental strain. Conjugal transfer of resistance from MP1 to a recipient strain was accompanied by acquisition in the transconjugants of amikacin phosphotransferase activity and of a 57-megadalton plasmid present in the donor. Partial purification of the phosphotransferase activity on amikacin-Sepharose 4B yielded an enzyme with a substrate spectrum similar to that of the 3'-neomycin-kanamycin phosphotransferase II found E. coli, except that it was also active against amikacin. A mutant of MP1, MP5, had increased susceptibility to amikacin and reduced phosphotransferase activity. MP9, a mutant MP5, was more resistant to amikacin and had increased phosphotransferase activity. The mutations leading to these alterations of amikacin susceptibility and amikacin phosphotransferase activity were transferable with the same plasmid that was associated with amikacin resistance and phosphotransferase activity in MP1. These studies demonstrate that resistance to amikacin in a laboratory strain of E. coli is due to an aminoglycoside phosphotransferase coded by a transferable plasmid-borne gene.
Disk diffusion testing of susceptibility of Mycobacterium fortuitum and Mycobacterium chelonei to antibacterial agents
Authors: Wallace R J , Dalovisio J R , Pankey G A
Published: June 2012

Although recent studies have suggested that some antibacterial agents have good activity against the rapidly growing mycobacteria Mycobacterium fortuitum and Mycobacterium chelonei, an easily applicable method for susceptibility testing of clinical isolates is not yet available. We evaluated a disk diffusion method with Mueller-Hinton agar and 48-h readings with 59 strains of M. fortuitum and 11 strains of M. chelonei and compared the results to agar dilution susceptibilities for nine antimicrobial agents. All isolates were susceptible to 16 micrograms of amikacin or kanamycin per ml with minimum zone diameters of 14 and 18 mm, respectively. Amikacin inhibited 100% of isolates of M. fortuitum at 2 micrograms/ml, whereas 10 of 11 (91%) of M. chelonei strains had minimum inhibitory concentrations of 4.0 micrograms/ml or greater. Doxycycline and minocycline had almost identical activities, inhibiting 44% of strains at 4.0 micrograms/ml, and both allowed easy differentiation between susceptible and resistant strains by disk diffusion. Although most isolates of M. chelonei grew better on 7H10 agar, this media gave two- to eight-fold higher minimum inhibitory concentrations than were obtained with Mueller-Hinton agar. Disk diffusion susceptibility testing appears to be a simple and reliable means of predicting susceptibility results for M. fortuitum and most isolates of M. chelonei by the agar dilution method.
Characterization and mode of action of a bacteriocin produced by a Bacteroides fragilis strain
Authors: Mossie K G , Jones D T , Robb F T , Woods D R
Published: June 2012

A Bacteroides fragilis strain produces a low-molecular-weight (13,500 to 18,700), proteinaceous bacteriocin during the stationary growth phase. The extracellular bacteriocin is not inducible by ultraviolet light or mitomycin C and is stable between pH 7.5 and 8.2. The majority of the bacteriocin is thermolabile, but a small proportion (3%) of the bacteriocin is stable after autoclaving at 121 degrees C for 15 min. Killing of sensitive bacteroides cells follows single-hit kinetics, and the interaction of a single molecule of bacteriocin with a target cell occurs in two stages. The killing of susceptible cells is affected by temperature and the growth state of the susceptible cells. The bacteriocin is unusual in that the primary event in its mode of action is the inhibition of RNA synthesis. The bacteriocin inhibits RNA synthesis immediately but has no effect on DNA synthesis or intracellular ATP levels. Protein synthesis is inhibited after a delay of 20 min, presumably as a result of the initial inhibition of RNA synthesis.
Rosaramicin Versus Penicillin G in Experimental Pneumococcal Meningitis
Authors: Nolan Charles M. , Monson Thomas P. , Ulmer W. Clyde
Published: June 2012

Rosaramicin, a new macrolide antibiotic, was compared with penicillin G in the treatment of pneumococcal meningitis in rabbits. Animals were infected intracisternally with 10
4
colony-forming units of
Streptococcus pneumoniae
type III (rosaramicin minimal inhibitory/bactericidal concentrations, 0.25/0.5 μg/ml; penicillin G minimal inhibitory/bactericidal concentrations, 0.03/0.06 μg/ml). Treatment was instituted 96 h later. Infusion of rosaramicin at 25 mg/kg per h intravenously for 8 h produced a peak cerebrospinal fluid (CSF) drug concentration of 1.54 μg/ml (range, 0.87-3.6 μg/ml). During this infusion the numbers of pneumococci in CSF decreased from 6.2 ± 0.5 to 3.36 ± 1.12 log
10
colony-forming units per ml. Penicillin G, infused at 30 mg/kg per h for 8 h, reached a similar concentration in CSF but caused a greater reduction (
P
< 0.01) in CSF bacteria, from 6.4 ± 0.36 to 1.3 ± 0.67 log
10
colony-forming units per ml. Penicillin G, at 100 mg/kg per day intramuscularly for 5 days, cured 7 of 10 rabbits with pneumococcal meningitis. A higher dose, 300 mg/kg per day for 5 days, was no more efficacious: 11 of 14 rabbits were cured. Rosaramicin at 100 mg/kg per day intramuscularly for 5 days cured only 5 of 15 rabbits with meningitis, but a higher dosage regimen of that drug (250 mg/kg per day intramuscularly) produced acute, fulminant enterocecitis and death within 48 h in seven of eight rabbits. No cytotoxin was detected in the feces of one rabbit with acute enterocecitis. Thus the efficacy of rosaramicin in experimental pneumococcal meningitis, measured by bacterial clearance from CSF and by treatment outcome, was less than that of penicillin G. In addition, high-dose parenteral rosaramicin caused acute, fulminant enterocecitis in a high proportion of treated rabbits.
Microbial transformation of A23187, a divalent cation ionophore antibiotic
Authors: Abbott B J , Fukuda D S , Dorman D E , Occolowitz J L , Debono M , Farhner L
Published: June 2012

A23187 is an ionophore antibiotic that forms dimeric complexes with divalent cations such an Mn2+ and Ca2+. Over 200 randomly selected soil microorganisms were incubated with A23187. None of these cultures was capable of transforming this compound. In contrast, many microorganisms were able to modify the methyl ester of A23187. The transformation products produced by one culture, Streptomyces chartreusis, were isolated and identified as 16-hydroxy-N-demethyl A23187 methyl ester, 16-hydroxy-A23187 methyl ester, and N-demethyl A23187 methyl ester. These ester derivatives lack most of the ionophore properties of the acids and cannot readily form dimeric complexes with divalent cations. However, they could be hydrolyzed by a mild treatment with ethanolic KOH to free acids that possess good ionophore activity. The use of the ester substrate in conjunction with the hydrolysis procedure is, at the present time, the only known method for microbiologically producing A23187 derivatives.
Triggering of autolytic cell wall degradation in Escherichia coli by beta-lactam antibiotics
Authors: Kitano K , Tomasz A
Published: June 2012

A biochemical method was developed to quantitatively compare the effectiveness of beta-lactams in triggering murein degradation (autolysin activity) in Escherichia coli. Bacteria prelabeled in their cell walls with radioactive diaminopimelic acid in growth medium were exposed for 10 min to the antibiotics at the appropriate minimal growth inhibitory concentrations and at multiples of these values, and the rate of cell wall degradation was followed during subsequent penicillin-binding protein (PBP)-1 were the most effective triggers of autolytic wall degradation; beta-lactams selective for PBP-2 were the poorest; and antibiotics preferentially binding to PBP-3 showed intermediate activities. The relative effectiveness of beta-lactams in autolysin triggering was found to parallel the effectiveness of the same drugs in causing rapid loss of viability, culture lysis, and spheroplast formation. Autolysin triggering was suppressed by inhibitors of protein and ribonucleic acid biosynthesis but not by inhibitors of deoxyribonucleic acid synthesis. The beta-lactam-induced cell wall degradation did not seem to involve a direct stimulation of enzyme activity or synthesis of new enzyme molecules, and murein sacculi isolated from cells that had been preexposed to a triggering dose of beta-lactam treatment exhibited the same sensitivity to crude, homologous autolysins as sacculi prepared from untreated control bacteria. On the basis of these observations, mechanisms are considered for the triggering of E. coli autolysins and for the role of autolytic activity in bacterial spheroplast formation, lysis, and death.
Effects of cerulenin on antibiotic-induced lysis of streptococcus faecalis (S. faecium)
Authors: Daneo-Moore L , Bourbeau P , Weinstein R , Carson D
Published: June 2012

Addition of the antibiotic cerulenin to cultures lowered the minimal effective concentration of penicillin G or methicillin required to produce bacterial lysis and killing. This effect was most pronounced at subinhibitory antibiotic concentrations. Cerulenin had no significant effects on lysis or killing induced in the presence of D-cycloserine, fosfomycin, bacitracin, or vancomycin.
Activity of ceftazidime (GR 20263) against nosocomially important pathogens
Authors: Hamilton-Miller J M , Brumfitt W
Published: June 2012

Ceftazidime was considerably more active than cefuroxime against 180 strains of resistant species of nosocomial gram-negative bacteria. In terms of antibacterial spectrum and intrinsic activity, ceftazidime is an improvement upon existing beta-lactam antibiotics in clinical use and can be regarded as a possible alternative to gentamicin.
Circular Dichroism Measurements of the Tetracyclines IV. 5-Hydroxylated Derivatives
Authors: Mitscher L. A. , Slater-Eng B. , Sokoloski T. D.
Published: June 2012

From extensive circular dichroism measurements of a variety of tetracycline (TC) derivatives in the presence and absence of a variety of chelating ions, it is concluded that 5-hydroxytetracycline possesses an identical solution conformation to that possessed by all fermentation-derived, bioactive TC species in dilute aqueous solutions at
p
H 7.5 or below. These conditions resemble those encountered under normal physiological circumstances. In alkaline solutions, the conformation of of 5-hydroxytetracycline diverges from the non-5-hydroxylated subclass of TC species. This divergence is rationalized as due to a buttressing effect of colinear
peri
-substituents at positions 4, 5, and 6 and is assisted by the possibility of hydrogen bonding between the 5 and 12a hydroxyl groups. Chelation, in alkaline solutions, with Mg ions “locks” the molecule into a conformation which has been detected by others in nuclear magnetic resonance studies in concentrated non-aqueous solvents and in X-ray studies with the 5, 12a-diacetoxy analogue. Parallel studies with a variety of model TC species and Ca ions provide strong support for the hypothesis that both Ca and Mg ions bind at the BCD juncture and that, above
p
H 7.5, the Ca ion binds to the A ring between 4-NMe
2
and 12a-OH, whereas Mg ion does not do this. If a 5-OH group is present, the Ca ion still binds as before, whereas the Mg ion will bind to the AB rings between 5-OH and 12a-OH. These factors are discussed in conjunction with the various conformations potentially available to the molecule.
Antibiotics from
Pseudomonas reptilivora
II. Isolation, Purification, and Properties
Authors: Del Rio Luís A. , Gorgé J. López , Olivares J. , Mayor F.
Published: June 2012

Under well-established culture conditions,
Pseudomonas reptilivora
produced several antibiotics that have been purified by solvent extraction, chromatography in Sephadex G-25, electrophoresis, and paper chromatography in different solvent systems. Activity has been monitored at the different steps of isolation and purification by measurement of the inhibition of the growth of
Staphylococcus aureus
by the cylinder-plate method, as well as by bioautography of chromatograms and electropherograms. Three antibiotics have been isolated and named A, B
1
, and B
2
. The B
1
and B
2
activities were studied in greater detail than A. The B
1
substance was crystallized, and its chemical properties were found to coincide with those of YC 73 or fluopsin C described by Egawa et al. and Itoh et al., respectively.
Inhibition of Vesicular Stomatitis Virus Replication by 9-β-
d
-Arabinofuranosyladenine
Authors: Grant J. A. , Sabina L. R.
Published: June 2012

9-β-
d
-Arabinofuranosyladenine (Ara-A) effectively inhibited the production of infectious vesicular stomatitis virus (VSV) in MDBK cells. Furthermore, inhibition was shown to begin as early as the first 3 hr of infection. Studies employing
3
H-
l
-leucine indicated that Ara-A did not affect protein synthesis in uninfected cells, although it did cause a marked stimulation of protein synthesis in VSV-infected cells during the log phase of the growth cycle. Puromycin, an inhibitor of protein synthesis, was a more effective viral inhibitor than Ara-A. However, the combination of Ara-A and puromycin was less effective than puromycin alone except when present for long time periods. Short-term labeling experiments with
3
H-uridine demonstrated that Ara-A depressed ribonucleic acid (RNA) synthesis in uninfected cells, whereas periods of stimulation and depression of radioisotope incorporation occurred in infected cells. The results support the notion that Ara-A is incorporated into RNA early during viral replication.
Transduction and Elimination of Resistance Determinants in Methicillin-Resistant
Staphylococcus aureus
Authors: Kayser Fritz H. , Wüst Jürg , Corrodi Peter
Published: June 2012

Elimination and transduction of drug resistance was examined in methicillin-resistant strains of
Staphylococcus aureus
. Irreversible spontaneous loss and “curing” by aging of cultures and by treatment with ethidium bromide indicated that the determinants for penicillinase production and chloramphenicol resistance, and probably also for neomycin resistance, were located extrachromosomally. On the other hand, the determinants of resistance to erythromycin, streptomycin, tetracycline, and methicillin could not be eliminated by acridines, ethidium bromide, rifampin, sodium dodecyl sulfate, ultraviolet (UV) irradiation, growth at 43.5 C, aging of cultures, or combinations of these treatments. The stimulation of transduction frequency by UV irradiation of phage in the case of the stable markers, but not in the case of the unstable ones, supported further the hypothesis of chromosomal location of the markers of methicillin, erythromycin, tetracycline, and streptomycin resistance and extrachromosomal location of the determinants for penicillinase production and chloramphenicol resistance. Neomycin resistance could not be transduced. Joint elimination and co-transduction of the determinants for penicillinase production and resistance to chloramphenicol and neomycin were not observed, indicating the location of these markers on separate, mutually compatible plasmids. Co-transduction of chromosomal resistance determinants was usually less than 1%, which makes the location of these genes in a circumscribed area of the chromosome improbable.
Susceptibility of
Chlamydia
to Antibacterial Drugs: Tests in Cell Cultures
Authors: Gordon Francis B. , Quan Alice L.
Published: June 2012

Concentrations of 20 μg of sulfadiazine or 30 μg of
d
-cycloserine/ml were found to be suitable for testing the differential susceptibility of
Chlamydia trachomatis
and
C. psittaci
to these drugs in cell cultures.
Mechanism of Action of Gliotoxin: Elimination of Activity by Sulfhydryl Compounds
Authors: Trown P. W. , Bilello J. A.
Published: June 2012

Gliotoxin and two other compounds, with antiviral activity against a number of ribonucleic acid (RNA) viruses and structurally related via the epidithiapiperazinedione moiety, appeared to be equally active in their oxidized and reduced forms. However, the ability of the reduced forms to inhibit viral RNA synthesis was abolished when these compounds were maintained in the reduced state by the simultaneous presence of a large molar excess of dithiothreitol or reduced glutathione. The active form therefore appeared to be that containing a disulfide bridge, and the apparent activity of the dithiol was due to cellular oxidation. Possible mechanisms by which the compounds could interact with viral proteins, e.g., viral RNA-dependent RNA polymerase, are proposed.
Metabolism of Indanyl Carbenicillin by Dogs, Rats, and Humans
Authors: Hobbs Donald C.
Published: June 2012

Indanyl carbenicillin, an ester of carbenicillin with indanol, is absorbed in the intestine after oral administration and is subsequently hydrolyzed to release the parent antibiotic which can be measured in serum and urine. To study the metabolism of indanyl carbenicillin, labeled indanol was prepared by exchange with tritiated water and was used, with phenylmalonyl chloride and 6-aminopenicillanic acid, to prepare labeled indanyl carbenicillin. Labeled indanol and indanyl carbenicillin were orally administered to dogs and rats with good recovery of label in the urine. In the dog, indanol, whether administered as such or as indanyl carbenicillin, was excreted in the urine as the glucuronide and sulfate ester conjugates of indanol and as conjugates of two hydroxyindanones and two hydroxyindanols, as determined by combined gas chromatography-mass spectrometry. Rats, conversely, excreted only the conjugates of indanol, whether indanol or indanyl carbenicillin was administered. After oral administration of unlabeled indanyl carbenicillin to humans, conjugates of indanol were recovered in the urine in excellent yield, as determined by a gas chromatographic assay. None of the other indanol metabolites formed by the dog was observed in human urine.
Comparative Activity of Sisomicin, Gentamicin, Kanamycin, and Tobramycin
Authors: Waitz J. Allan , Moss E. L. , Drube C. G. , Weinstein M. J.
Published: June 2012

Gentamicin, sisomicin, tobramycin, and kanamycin were compared in parallel tests in vitro and in vivo against a variety of bacterial strains and species. A number of differences were seen in vitro, in particular: (i) the lower activity of kanamycin, (ii) the greater activity of tobramycin against
Pseudomonas
, (iii) the greater activity of gentamicin and sisomicin against
Serratia
, and (iv) the generally similar results with tobramycin, gentamicin, and sisomicin against species other than
Pseudomonas
and
Serratia
, with the ranking in order of decreasing activity being sisomicin, gentamicin, and tobramycin. Analysis of disc test results suggested that the gentamicin disc is not adequate for testing the susceptibility of all bacteria to sisomicin or tobramycin. In vivo tests did not confirm all specifics of in vitro tests; results of in vivo tests indicated that sisomicin may be the most active. It is suggested that the place of each of the antibiotics in human therapy can best be evaluated by more rigorous in vivo tests and clinical studies rather than extensive in vitro comparisons.
Mode of Action of a
Staphylococcus epidermidis
Bacteriocin
Authors: Jetten A. M. , Vogels G. D.
Published: June 2012

Staphylococcin 1580, a bacteriocin produced by
Staphylococcus epidermidis
1580, is bactericidal to sensitive cells of many gram-positive bacteria and stable staphylococcal L-forms. The bacteriocin inhibited simultaneously the syntheses of deoxyribonucleic acid, ribonucleic acid, and protein, and caused neither degradation of deoxyribonucleic acid nor induction of phages in lysogenic, sensitive cells. After 1 hr of treatment, extensive degradation of ribonucleic acid occurred, which was accompanied by leakage of ultraviolet-absorbing material out of the cell. The incorporation of glucose in acid-precipitable and glycogenlike material was inhibited. Furthermore, the staphylococcin inhibited the transport of glucose, glutamic acid, rubidium ions, and
o
-nitrophenyl-β-galactoside. The uptake of oxygen was only gradually affected, but the intracellular adenosine triphosphate level fell rapidly to 15% of the control value. The motility of sensitive
Bacillus subtilis
cells was markedly reduced on treatment. Staphylococcin 1580 exhibited no phospholipase activity. The phenomena are interpreted as resulting from an altered conformation and composition of the membrane, from an inhibition of transport through the membrane, or from a combination of these effects.
Limiting Reactions in Activation of Acyl Units in Biosynthesis of Macrolide Antibiotics
Authors: Raczyńska-Bojanowska Konstancja , Ruczaj Zbigniew , Sawnor-Korszyńska Danuta , Rafalski Andrzej
Published: June 2012

Formation of propionyl phosphate in
Streptomyces erythreus
synthesizing a polypropionate erythronolide ring of erythromycin was found to be catalyzed by a specific propionate kinase. The isolated and 100-fold purified kinase was devoid of activity towards acetate and other monocarboxylic acids. The selection for higher antibiotic-synthesizing ability was associated with higher kinase activity and lower

K
m

values towards propionate. This relation did not apply to the mutants of
S. noursei
var.
polifungini
producing polyene tetraene antibiotics of the nystatin type, composed of acetate and propionate units. Instead, the antibiotic-synthesizing ability was correlated with the activity of acetyl- and propionyl-coenzyme A carboxylase, responsible for the formation of malonyl- and methyl-malonyl-coenzyme A intermediates in the polymerization process.
Clinical and In Vitro Evaluation of Cefazolin, a New Cephalosporin Antibiotic
Authors: Ries Kristen , Levison Matthew E. , Kaye Donald
Published: June 2012

Cefazolin sodium, a cephalosporin for parenteral use, was evaluated in vitro and in 26 patients. Cefazolin had activity equivalent to cephalothin against
Streptococcus pneumoniae, Staphylococcus aureus
, group A streptococci, and
Proteus mirabilis
. Cefazolin was four- to eightfold more active against
Escherichia coli
and slightly more active against
Klebsiella pneumoniae
, whereas cephalothin was slightly more active against indole-positive
Proteus
species. After a 500-mg dose of cefazolin intramuscularly, peak concentrations in the serum were high enough to inhibit all strains of
S. pneumoniae, S. aureus
, group A streptococci,
E. coli, K. pneumoniae
, and
P. mirabilis
, as well as 60% of strains of
Proteus
species other than
P. mirabilis
. All of 26 patients (18 with pneumonia, 6 with urinary tract infection, and 2 with skin infections) responded clinically and bacteriologically to cefazolin therapy. There were no major side effects of therapy, and no patient complained of pain at the site of intramuscular injection. Cefazolin is an effective cephalosporin which can be used intramuscularly for therapy of serious bacterial infections. Its major advantages over other cephalosporins are higher, more sustained concentrations in the blood and apparent lack of pain on intramuscular injection.
Cephacetrile: Clinical Evaluation in 27 Patients
Authors: Hodges Glenn R. , Scholand Joseph F. , Perkins Robert L.
Published: June 2012

Cephacetrile, a new derivative of 7-aminocephalosporanic acid, was evaluated in 27 patients. Soft tissue infections due primarily to gram-positive cocci were treated in 16 patients; 12 had bacteriological and clinical cure, and 4 improved but the lesions resolved incompletely or cultures remained positive. Seven of eight patients with respiratory tract infections were cured, including three with pneumococcal pneumonia; the eighth proved to have a noninfectious process and failed to respond. Two patients with acute urinary tract infections due to
Escherichia coli
had prompt clinical and bacteriological improvement, but follow-up was incomplete. One patient with sepsis due to
Staphylococcus aureus
expired. Laboratory abnormalities observed during cephacetrile therapy included mild eosinophilia in four patients, thrombocytosis in nine, direct Coombs' test positivity in four, and an elevated serum glutamic pyruvic transaminase in eight patients. No evidence of nephrotoxicity was detected. Severe superinfection due to
Enterobacter
species was observed in one patient. Mean peak serum concentrations of cephacetrile were 22, 69, and 104 μg/ml after 1 g intramuscularly, 1 g intravenously, and 1.5 g intravenously, respectively. Thus, in early studies cephacetrile was efficacious for selected bacterial infections, but determination of its comparative value within the cephalosporin group of antibiotics requires further clinical investigation.