bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Long-Term Therapies with Penicillin and Sulfadiazine on
Streptococcus mutans
and Lactobacilli in Dental Plaque
Authors: Weld H. G. , Sandham H. J.
Published: June 2012

Plaque samples were obtained from 13 children receiving long-term therapy with benzathine penicillin for the prevention of rheumatic fever recurrences, 31 children receiving oral sulfadiazine for the same purpose, and 29 untreated siblings. The therapies were found to have no effect upon the proportions of
Streptococcus mutans
or lactobacilli in dental plaque, upon the percentage of children harboring the organisms, nor upon the susceptibility of the organisms to penicillin and sulfadiazine. Of the
S. mutans
strains tested, 97% had a minimal inhibitory concentration of penicillin G of less than 48 ng/ml and, of the lactobacillus strains tested, 96.8% had a minimal inhibitory concentration of less than 1,600 ng/ml. All strains of both organisms were profoundly resistant to sulfadiazine.
Chloramphenicol: an Enzymological Microassay
Authors: Lietman Paul S. , White Thomas J. , Shaw William V.
Published: June 2012

A new assay for chloramphenicol in biological fluids has been developed that offers sensitivity, specificity, precision, accuracy, economy, and ease of performance. The assay is based on the enzymological acetylation of chloramphenicol catalyzed by an R factor-mediated enzyme. [
14
C]acetyl coenzyme A serves as the donor of the labeled acetyl group, and the product, [
14
C]acetoxychloramphenicol, is separated from the labeled precursor by utilizing its preferential extraction into benzene. The product is then quantified by liquid scintillation counting. This assay measures chloramphenicol concentrations in both plasma and other biological specimens and in the presence of other antibiotics, hemolysis, or jaundice. Its rapidity and ease of performance are useful for clinical laboratories, and its sensitivity allows determinations on 10 μl of plasma.
In Vitro Susceptibility of Pathogenic
Naegleria
and
Acanthamoeba
Species to a Variety of Therapeutic Agents
Authors: Duma Richard J. , Finley Ruth
Published: June 2012

Six pathogenic strains of
Naegleria fowleri
, two of
Acanthamoeba castellanii
, and three of
Acanthamoeba polyphaga
were tested in vitro for susceptibility to a variety of potentially useful therapeutic agents. Minimal motility inhibitory concentrations and minimal inhibitory concentrations were determined by a technique of subculturing pure clones of amoebae in plastic tissue culture chamber slides containing liquid axenic media and serially diluted drug, incubating at 30°C for
Acanthamoeba
and at 37°C for
Naegleria
, and observing on an inverted microscope at 6 h for inhibition of motility and at 24 and 48 h for inhibition of growth. Drug concentrations were selected on the basis of fluid levels achievable in humans. Amphotericin B, clotrimazole, and miconazole were the most effective drugs against
Naegleria
, whereas polymyxin B sulfate and pentamidine isethionate were somewhat effective against pathogenic
Acanthamoeba
. Our results suggest that amphotericin B is the most effective agent against
Naegleria
, but few agents are effective against
Acanthamoeba
.
Genotypic Stability of Methicillin Resistance in
Staphylococcus aureus
at Supraoptimal Temperature
Authors: Rozgonyi Ferenc
Published: June 2012

Methicillin resistance in a highly resistant mutant of
Staphylococcus aureus
could not be diminished by elevated temperature. After 100 subcultures at 43°C the resistance to methicillin was retained when determined at 37°C.
Comparative In Vitro Activity of Sch 20656, Netilmicin, Gentamicin, and Tobramycin
Authors: Watanakunakorn Chatrchai
Published: June 2012

Sch 20656 and netilmicin (Sch 20569), two new semisynthetic aminoglycosides, were as active as gentamicin and tobramycin against
Enterobacteriaceae
. Against
Pseudomonas aeruginosa
, Sch 20656 was the least active, whereas netilmicin was active against many highly gentamicin-resistant isolates.
Inhibition of the Apparent Rate of Synthesis of the Vacuolar Glycoprotein Carboxypeptidase Y and Its Protein Antigen by Tunicamycin in
Saccharomyces cerevisiae
Authors: Hasilik Andrej , Tanner Widmar
Published: June 2012

Carboxypeptidase Y from
Saccharomyces cerevisiae
contains 14% mannose, the only neutral sugar present. An antiserum can be raised in rabbits which reacts with both the protein and the sugar moieties of the enzyme. This antiserum also precipitates yeast invertase and yeast cell wall mannan. Thus carboxypeptidase Y, which is known to be localized in yeast vacuoles, is very probably a mannoprotein. Tunicamycin inhibits the apparent formation of carboxypeptidase Y to a similar extent as that of the externally localized mannoprotein, invertase. No accumulation of an inactive nonglycosylated or partly glycosylated carboxypeptidase Y occurs as determined by the immunoprecipitation technique. Tunicamycin also inhibits the apparent formation of proteinase A, whereas it does not affect the increase in the activities of a number of other enzymes. It is suggested that in the synthesis of glycoproteins there exists a regulatory link between the synthesis of their polypeptide chains and the reactions involved in their glycosylation.
Active Metabolites of Isoxazolylpenicillins in Humans
Authors: Thijssen H. H. W. , Mattie H.
Published: June 2012

Metabolites of the isoxazolylpenicillins that still possessed antibacterial activity were shown to be present in urine and serum. In healthy subjects, the amounts excreted in urine were low; 10 to 23% of the excreted penicillin activities represented the metabolites. The highest amount of metabolite in urine was found for oxacillin, and the lowest was found for flucloxacillin. No extreme differences in the amounts of metabolite excreted were observed when the compounds were administered orally or intravenously. In one healthy subject metabolite levels were estimated for cloxacillin in serum. Very low levels were found, i.e., about 9% of the activity. In subjects with highly impaired renal function, the metabolite may represent up to 50% of the total level of penicillin in serum. The antibacterial activities of the different metabolites were of the same order of magnitude as those of the respective parent compounds. Also, the activity against benzylpenicillin-resistant staphylococci was retained. It is not likely that the formation of the active metabolites should influence therapeutic results.
Pharmacokinetics of Cefamandole in Patients Undergoing Hemodialysis and Peritoneal Dialysis
Authors: Ahern Mary Jean , Finkelstein Frederic O. , Andriole Vincent T.
Published: June 2012

The pharmacokinetics of cefamandole nafate, a new parenteral cephalosporin derivative, were evaluated in 11 patients with chronic renal failure (creatinine clearance less than 5 ml/min), including five patients during hemodialysis, four patients during routine peritoneal dialysis, and two patients during the interdialytic period. Peak serum levels of cefamandole were comparable to those observed in patients with normal renal function. Clearance of the drug during the interdialytic period and during hemodialysis and peritoneal dialysis was minimal, with a resultant significant prolongation of serum half-life. The nondialyzability of cefamandole is in contrast with reported studies of cephalothin, where significant reduction of the serum half-life was achieved during hemodialysis but not peritoneal dialysis. The concentration of cefamandole in the peritoneal dialysate after parenteral administration was observed to be bactericidal for many gram-negative pathogens and, with the exception of
Streptococcus faecalis
, most gram-positive organisms found in bacterial peritonitis in patients with severe renal failure. The present data suggest that if stable bactericidal serum levels of cefamandole are to be maintained during hemodialysis and peritoneal dialysis, a parenteral loading dose must be administered followed by one-half the loading dose every half-life.
Basis for the Design of Anticandidal Agents from Studies of Peptide Utilization in
Candida albicans
Authors: Lichliter Wayne D. , Naider Fred , Becker Jeffrey M.
Published: June 2012

The growth of
Candida albicans
WD 18-4, a methionine and lysine double auxotroph, on a variety of methionine- and lysine-containing peptides was determined. This yeast does not excrete extracellular peptidases. Thus, the growth response to peptides containing the required amino acid is a measure of peptide transport. A variety of methionine-containing peptides such as Met-Met, Met-Met-Met, and Met-Met-Met-Met-Met are transported. Acylation of the N-terminus of transported peptides does not affect their transport, but derivitization of the C-terminus prevents peptide uptake. In contrast, all lysine-containing peptides tested, except Lys-Gly, were not growth substrates. The inability of a peptide to substitute for the requisite amino acid was not due to the absence of cellular peptidases or to toxicity of the nonutilized peptides. Several potentially toxic amino acids were carried into
Candida
as a component of transported peptides. This establishes the peptide transport system as a possible tool for the design of antibiotics for
Candida albicans
.
Inhibition of Antibiotic Activity In Vitro by Synthetic Melanin
Authors: Barza Michael , Baum Jules , Kane Anne
Published: June 2012

Synthetic melanin (100 to 1,000 μg/ml) markedly inhibited the in vitro activity of aminoglycosides and tetracyclines but did not affect the activity of betalactam antibiotics, erythromycin, or clindamycin.
Classification of R Plasmids by Incompatibility in
Pseudomonas aeruginosa
Authors: Sagai H. , Hasuda K. , Iyobe S. , Bryan L. E. , Holloway B. W. , Mitsuhashi S.
Published: June 2012

R plasmids identified in
Pseudomonas aeruginosa
strains isolated in our laboratories were classified by their incompatibility characters by using intraspecies conjugation in
P. aeruginosa
. The fertility factor, FP2, was compatible with R plasmids belonging to all groups, and was classified in a new group. From these data, the plasmids examined have been placed into seven or eight incompatibility groups.
Comparative Activity of Netilmicin, Gentamicin, Amikacin, and Tobramycin Against
Pseudomonas aeruginosa
and
Enterobacteriaceae
Authors: Briedis Dalius J. , Robson Hugh G.
Published: June 2012

Netilmicin (Sch 20569), a semisynthetic aminoglycoside antibiotic, was compared with gentamicin, tobramycin, and amikacin against 242 clinical isolates of
Pseudomonas
and
Enterobacteriaceae
. The minimum inhibitory concentration (MIC) was determined in both solid and liquid media. Netilmicin exhibited typical aminoglycoside properties, such as little effect of inoculum size on MIC, relatively small gap between MIC and minimum bactericidal concentration, and potentiation of anti-
Pseudomonas
activity in the presence of carbenicillin. Netilmicin provided no advantage in antimicrobial activity over gentamicin for either
Pseudomonas
or
Enterobacteriaceae
. Nearly complete cross-resistance to netilmicin was encountered with isolates resistant to gentamicin in either solid or liquid media. Netilmicin was less active than gentamicin against isolates of
Pseudomonas
and
Providencia
. Major discrepancies between MIC values determined in agar as opposed to those determined in broth were encountered for most isolates of
Pseudomonas
but also, depending upon antibiotic tested, for between 15 and 40% of isolates of
Enterobacteriaceae
. This new aminoglycoside agent will be useful clinically only if it is shown to be significantly less toxic than presently available analogues.
Enzymatic Adenylylation by Aminoglycoside 4′-Adenylyltransferase and 2′′-Adenylyltransferase as a Means of Determining Concentrations of Aminoglycoside Antibiotics in Serum
Authors: Santanam P. , Kayser F. H.
Published: June 2012

A fast and accurate enzymatic estimation of the concentration of aminoglycoside antiobiotics in serum is given by aminoglycoside 4′-adenylyltransferase (synonym: tobramycin adenylyltransferase), a new enzyme recently found in tobramycin-resistant staphylococci (P. Santanam and F. H. Kayser, J. Infect. Dis. [Suppl.], in press). This enzyme is useful in assaying the kanamycins, the butirosins, amikacin, ribostamycin and, if required, the neomycins, tobramycin, and paromomycin. In combination with the assay using aminoglycoside 2′′-adenylyltransferase (synonym: gentamicin adenylyltransferase) to determine the level of gentamicin, sisomicin, and tobramycin, a convenient method to estimate a wide range of aminoglycoside antibiotics in patients' sera is described.
Aerobically Incubated Thioglycolate Broth Disk Method for Antibiotic Susceptibility Testing of Anaerobes
Authors: Kurzynski Terrence A. , Yrios John W. , Helstad Arlan G. , Field Charles R.
Published: June 2012

The anaerobic broth disk (AnBD) method of Wilkins and Thiel and a new modification, designated the thioglycolate broth disk method, were compared with an agar dilution technique. The thioglycolate broth disk method was incubated aerobically (AeTBD) or anaerobically (AnTBD). One hundred anaerobic bacteria representing 15 species were tested with clindamycin, chloramphenicol, erythromycin, penicillin, and tetracycline. Agreement of results by the two methods with minimal inhibitory concentration determinations were: AnBD, 95.2%; AnTBD, 91.5%; AeTBD, 94.5%. With clindamycin, chloramphenicol, and penicillin, the agreement of the AeTBD and agar dilution results was 100%, 100%, and 95%, respectively. Using the AeTBD method, only 1.1% of all tests gave false susceptible readings, whereas 4.4% gave false resistant readings. All susceptibility testing errors occurred with tetracycline, erythromycin, and, to a lesser extent, penicillin. For each method, the changes in designation of bacteria as being susceptible or resistant to an antibiotic between trials primarily involved strains with minimal inhibitory concentrations which were ± one dilution of the respective breakpoint value. The same situation was true for most bacteria that yielded false resistant readings within each trial. False resistant readings with tetracycline were determined to be unrelated to excess cation content of test media. These results reaffirm the reliability of the AnBD method and indicate that the AeTBD modification is equally reliable. The greater convenience and lower cost of the AeTBD method should make possible more widespread performance of susceptibility testing for anaerobic bacteria in hospital laboratories.
Concentration of Cefamandole in Serum Interstitial Fluid, Bile, and Urine
Authors: Waterman N. G. , Eickenberg H. U. , Scharfenberger L.
Published: June 2012

Cefamandole readily diffuses from the serum into soft tissue interstitial fluid. The rate of diffusion differs little from that of cephalothin. The concentrations of antibiotic were greater in bile and urine during the entire period of study than is necessary to kill susceptible pathogenic bacteria present in these fluids.
Antibiotic Penetrance of Ascitic Fluid in Dogs
Authors: Gerding Dale N. , Kromhout James P. , Sullivan John J. , Hall Wendell H.
Published: June 2012

Antibiotic concentrations in ascitic fluid after parenteral therapy may be important in the treatment of peritonitis. We have created ascites in dogs by partial ligation of the inferior vena cava. Ascitic fluid volume was measured at the time each antibiotic was administered. Nine antibiotics were studied in the same three dogs. Antibiotic concentration in ascitic fluid was found to vary inversely with ascites volume. Percentage of penetration (ratio of ascites peak to serum peak ×100) ranged from 5.8 to 65% among the drugs studied. Only metronidazole showed a statistically significant higher percentage of penetration than other antimicrobials. Concentrations in ascitic fluid after single doses of cephalothin (15 mg/kg) and the aminoglycosides (2 mg/kg, gentamicin and tobramycin; 7.5 mg/kg, amikacin and kanamycin) did not exceed the minimum inhibitory concentration of many gram-negative rods and may justify the use of higher than usual initial parenteral doses, or possibly initial intraperitoneal administration in seriously ill patients.
Sisomicin Versus Netilmicin: In Vitro Susceptibility Testing
Authors: Flournoy D. J.
Published: June 2012

Antimicrobial susceptibility to sisomicin and netilmicin (Sch 20569) was determined on 164 clinical isolates using a broth microdilution method. Sisomicin was active against 86.1%, and netilmicin against 96.4%, of the isolates. In addition, netilmicin was active against 93.7% of the strains that were resistant to gentamicin, kanamycin, tobramycin, and sisomicin.
Comparative In Vitro Studies of Cinoxacin, Nalidixic Acid, and Oxolinic Acid
Authors: Gordon Ralph C. , Stevens Lynne I. , Edmiston Charles E. , Mohan Kanwal
Published: June 2012

Cinoxacin and nalidixic acid were found to be similar in in vitro activity against 138
Shigella
isolates and somewhat less active than oxolinic acid on a weight basis. Cross-resistance developed when 10 shigellae were transferred on increasing amounts of the respective agent contained in Mueller-Hinton agar. Plate dilution studies of the effect of changes in agar pH on the minimum inhibitory concentration revealed that the antibacterial activity increased with decreasing pH. Protein binding investigations revealed a high degree of binding, with nalidixic acid > oxolinic acid > cinoxacin.
Temperature-Sensitive R Plasmid Obtained from Naturally Isolated Drug-Resistant
Vibrio cholerae
(Biotype El Tor)
Authors: Yokota Takeshi , Kuwahara Shogo
Published: June 2012

A temperature-sensitive
fi
−
R plasmid, pJY1, which confers resistance to chloramphenicol, streptomycin, and sulfonamide, was found in a drug-resistant strain of
Vibrio cholerae
(biotype El Tor) isolated in the Philippines in 1973. The R plasmid is temperature sensitive for transferability but not for stability in the hosts. pJY1 is stably maintained either in
V. cholerae
or in
Escherichia coli
at a range of culture temperatures from 27 to 42°C. Compatibility tests with reference R plasmids revealed that pJY1 belongs to the J group. Growth of
V. cholerae
carrying pJY1 is poor on TCBS (thiosulfate-citrate-bile-sucrose) selective plates when the microbe is subcultured in nutrient broth at temperatures higher than 37°C.
Susceptibility of
Propionibacterium acnes
to Seventeen Antibiotics
Authors: Wang Wen Lan Lou , Everett E. Dale , Johnson Marcia , Dean Evelyn
Published: June 2012

The in vitro susceptibility of 96 isolates of
Propionibacterium acnes
to 17 antibiotics was determined by utilizing an agar dilution technique. With the exception of the aminoglycosides, these organisms are susceptible to virtually all of the commonly used antimicrobial agents.
Stability of Cephalosporins in Horse Serum
Authors: Foglesong M. A.
Published: June 2012

The antibiotic activity of cephalothin, cephaloridine, cephalexin, cephaloglycin, cefazolin, and cefamandole was determined after storage for up to 30 days in horse serum at −10 and 4°C. Cephalothin, cefamandole, cefazolin, and cephalexin were stable for at least 30 days at −10°C, whereas cephaloridine lost 29% of its initial activity and cephaloglycin lost more than 50%. Cefamandole, cefazolin, and cephalexin could only be stored for 3 days at 4°C without significant loss in activity, whereas cephalothin, cephaloridine, and cephaloglycin could be stored for only 1 day. Repeated freezing and thawing had a detrimental effect on the stability of cephaloridine.
Therapy of Murine Aspergillosis with Amphotericin B in Combination with Rifampin or 5-Fluorocytosine
Authors: Arroyo Julio , Medoff Gerald , Kobayashi George S.
Published: June 2012

Suboptimal doses of amphotericin B in combination with either rifampin or 5-fluorocytosine were better than single-drug therapy in the treatment of disseminated
Aspergillus fumigatus
infection in mice. Despite the increased effectiveness of combination therapy, none of the therapeutic regimens we used completely eradicated infections in the mice when evaluated by mycological culture, even in long-term survivors.
In Vitro Studies with Netilmicin Compared with Amikacin, Gentamicin, and Tobramycin
Authors: Dhawan Vijay , Marso Eugene , Martin William J. , Young Lowell S.
Published: June 2012

Netilmicin, a new semisynthetic aminoglycoside derived by ethylation of the 1-
N
position of the deoxystreptamine ring of sisomicin, was tested in vitro with 4,070 strains of gram-negative bacilli isolated at the UCLA Medical Center during 1975 to 1976, using the agar dilution technique and an inoculum of approximately 10
4
organisms. Results were compared with those simultaneously obtained for amikacin, gentamicin, and tobramycin. Using Mueller-Hinton medium, inhibitory concentrations in broth correlated with those obtained by the agar dilution method except for
Pseudomonas aeruginosa
, where a 2- to 16-fold difference in susceptibility was noted. For most clinically significant
Enterobacteriaceae
and
P. aeruginosa
, the activity of netilmicin in vitro was comparable or superior to that of gentamicin, tobramycin, and amikacin with respect to potency by weight and achievable blood levels. Against gentamicin-resistant strains (MIC > 16 μg/ml), the activity of netilmicin paralleled that of amikacin with the exception of
Providencia stuartii
, which was inhibited by amikacin but not by netilmicin.
Susceptibility of Three Groups of
Staphylococcus aureus
to Newer Antimicrobial Agents
Authors: Jordan George W. , Hoeprich Paul D.
Published: June 2012

Because of the need for non-β-lactam antimicrobics with antistaphylococcal activity, 14 antimicrobics (3 penicillinase-resistant penicillins, 7 aminocyclitols [5 new], 2 macrolides [1 new], clindamycin, and a new polysaccharide, everninomicin) were tested in vitro for activity against 22 penicillin-susceptible, 51 penicillin-resistant, and 47 methicillin-resistant strains of
Staphylococcus aureus
. Gentamicin, tobramycin, sisomicin, and verdamicin inhibited almost all strains at concentrations less than 1 μg/ml. The methicillin-resistant strains were as susceptible as other strains to the aminocyclitols and everninomicin. In contrast, many of the methicillin-resistant strains were also resistant to erythromycin, rosamicin, and clindamycin at attainable serum concentrations. The use of the bacterial synthetic amino acid medium, in comparison with Mueller-Hinton broth, resulted in an increase in the observed resistance of methicillin-resistant strains to the penicillinase-resistant semisynthetic penicillins.
Comparative Study of the Antiviral Activity of Acyl Derivatives of 2,2′-Anhydro-1-β-
d
-Arabinofuranosylcytosine and Other Nucleosides Against Encephalitis in Mice
Authors: Nishiyama Shinya , Sato Kosaburo , Yamanaka Toshihiko , Moffatt John G.
Published: June 2012

Anti-deoxyribonucleic acid virus activities of 3′-
O
-acyl derivatives of 2,2′-anhydro-1-β-
d
-arabinofuranosyl cytosine (cyclo-C) and 1-β-
d
-arabinofuranosylcytosine (Ara-C) were evaluated by using an in vivo test system in mice. Among the derivatives tested, 3′-
O
-decanoyl cyclo-C hydrochloride was the most effective against herpes simplex virus-induced encephalitis in mice when the drug was administered directly into infected brains of mice (target-organ treatment). A comparative study of the treatment of herpetic encephalitis in mice with 3′
O
-decanoyl cyclo-C and other nucleosides, including Ara-C, 9-β-
d
-arabinofuranosyladenine (Ara-A), and 5-iodo-2′-deoxyrudine (IUdR), proved Ara-A to be more efficacious than the other nucleosides, followed by 3′-
O
-decanoyl cyclo-C, which was more active than Ara-C and IUdR. Administration of 3′-
O
-acyl cyclo-C's by intraperitoneal injection, however, failed to demonstrate activity against herpetic encephalitis in mice. The antivaccinial activity of 3′-
O
-decanoyl cyclo-C was also compared with that of other compounds against encephalitis and dermal tail lesions in mice caused by vaccinia virus infection. Interaperitoneally administered 3′-
O
-decanoyl cyclo-C and Ara-C also showed no significant activity against the diseases. Under these test conditions,
N
-methylisatin-β-thiosemicarbazone (Marboran) was the most active compound, followed by Ara-A.
Pharmacokinetics of Cefamandole in Patients with Renal Failure
Authors: Meyers Burt R. , Hirschman Shalom Z.
Published: June 2012

The pharmacokinetics of cefamandole were studied in four patients with stable renal failure, two patients undergoing peritoneal dialysis, and four patients undergoing hemodialysis. Peak concentrations of cefamandole in serum were achieved 1 to 2 h after intramuscular injection in the patients with stable renal impairment, and the concentrations declined slowly, with half-life values of 12.3 to 18 h. Cefamandole was removed only very slowly by peritoneal dialysis. Hemodialysis was more efficient in removing cefamandole, with serum half-life values ranging from 3.8 to 7.9 h. The mean apparent volume of distribution of cefamandole in these 10 patients was 21.92 liters, or 31% of the body weight.
Transfer of a Plasmid-Specified Beta-Lactamase Gene from
Haemophilus influenzae
Authors: Saunders J. R. , Sykes R. B.
Published: June 2012

A number of ampicillin-resistant strains of
Haemophilus influenzae
could donate a gene specifying the type IIIa (TEM) β-lactamase to
Haemophilus parainfluenzae, Escherichia coli
, and
Pseudomonas aeruginosa
. Donor strains rapidly lost their ability to transfer ampicillin resistance on storage or subculture. Such strains also apparently contained a single species of covalently closed circular deoxyribonucleic acid of contour length 1.2 μm, equivalent to about 2.5 × 10
6
daltons. No species of plasmid deoxyribonucleic acid large enough to encode sex factor activity was detected. Despite this, transfer occurred to several bacterial genera in the presence of deoxyribonuclease, suggesting that transmissibility was by conjugation. The β-lactamase gene was generally unstable after transfer and was lost in the absence of selection. Where stable transcipients were found, this was evidently by insertion of the β-lactamase gene into the host chromosome. In
P. aeruginosa
insertion was always accompanied by induction of auxotrophy for adenine, suggesting insertion at a specific site. It is believed that insertion also occurred at one site on the chromosome of
Escherichia coli
. Crypticity measurements for β-lactamase activity showed that there was little or no penetration barrier to β-lactam drugs in
Haemophilus
. This may explain the long delay in the acquisition of ampicillin resistance by this organism.
In Vitro Activity of Netilmicin
Authors: Smith J. A. , Morgan J. R. , Mogyoros M.
Published: June 2012

The activity of netilmicin against a variety of bacteria was similar to that of gentamicin, sisomicin, and tobramycin, but it was less active than these three drugs against
Pseudomonas aeruginosa
. Synergy with penicillin G against enterococci was demonstrated.
Inhibition of Initiation, Elongation, and Termination of Eukaryotic Protein Synthesis by Trichothecene Fungal Toxins
Authors: Cundliffe Eric , Davies Julian E.
Published: June 2012

The 12,13-epoxytrichothecenes, specific inhibitors of protein synthesis in eukaryotes, can be subdivided further in terms of their mode of action. In addition to the I-type (initiation inhibitors) and E-types (elongation inhibitors), we found that some E-types apparently exhibit inhibition of chain termination at low concentrations. The nature of substituents on C4 may determine the type of inhibitory activity observed.
Cerulenin-Inhibited Cells of
Staphylococcus aureus
Resume Growth When Supplemented with Either a Saturated or an Unsaturated Fatty Acid
Authors: Altenbern Robert A.
Published: June 2012

In the presence of an inhibitory concentration of cerulenin, cells of
Staphylococcus aureus
can resume growth when supplemented with either a saturated or an unsaturated fatty acid. A requirement for both types of acids for growth could not be demonstrated.
Comparative Activity of Ampicillin and Cefuroxime Against Three Types of
Haemophilus influenzae
Authors: Sykes R. B. , Griffiths A. , Ryan D. M.
Published: June 2012

On the basis of their susceptibility to ampicillin, strains of
Haemophilus influenzae
can be divided into three types: type 1 are normally susceptible strains, type 2 produce stable spheroplasts from low inocula, and type 3 are β-lactamase producers. Because of the production of spheroplasts, standard broth and agar dilution techniques have failed to differentiate between the responses of type 2 and 3 strains to ampicillin, or to identify the superiority of cefuroxime over ampicillin against the β-lactamase-producing strains. Disk susceptibility tests with heavily seeded plates were also difficult to interpret. To overcome these problems, we developed a medium that supports the growth of
H. influenzae
, but not survival of spheroplasts, thereby reducing the complicating influence of spheroplast formation. Utilization of the medium made it possible to identify β-lactamase-producing strains via both minimal inhibitory concentration and disk susceptibility techniques, as well as the superiority of cefuroxime over ampicillin against such strains. In vivo experiments showed that cefuroxime and ampicillin are equally active against infections with type 1 and 2 strains, but that cefuroxime is superior to ampicillin against infections with type 3 β-lactamase-producing strains.
Penicillin Resistance and Penicillinase Production in Clinical Isolates of
Bacteroides melaninogenicus
Authors: Murray Patrick R. , Rosenblatt Jon E.
Published: June 2012

The minimum inhibitory concentrations (MIC) of penicillin and six other antimicrobials were determined for 50 clinical isolates of
Bacteroides melaninogenicus
. Agar dilution susceptibilities were performed using supplemented brucella blood agar and the proposed National Committee for Clinical Laboratory Standards standard method for anaerobes; results with the two methods were comparable. A penicillin concentration ≥0.8 μg/ml was needed to inhibit 56% of the isolates, whereas 100% were susceptible to 0.1 μg of clindamycin per ml. All isolates with penicillin MIC values ≥0.8 μg/ml produced β-lactamase using a slide method. A micro-iodometric assay was used to quantitate β-lactamase production in six isolates. The β-lactamase activity of
B. melaninogenicus
was comparable to that of a
Staphylococcus aureus
isolate but was not inducible, and the specific amount produced correlated only partially with penicillin MIC values. A clinical review of patients from whom the β-lactamase-producing strains of
B. melaninogenicus
were isolated did not suggest any increased virulence in these strains or an unexpectedly poor clinical response to appropriate therapy.
Macrolide Resistance in
Staphylococcus aureus
: Inducers of Macrolide Resistance
Authors: Allen Norris E.
Published: June 2012

Several macrolide-, lincosamide-, and streptogramin B-type (MLS) antibiotics were tested as inducers of erythromycin A (EM)-resistant [
14
C]leucine incorporation. Only 14-membered-ring macrolides having a glycosidically linked 6-deoxy sugar at the C-3 position of the lactone ring and the structurally dissimilar lincosamide, celesticetin, showed inducer activity. Modifications of EM at the C-4″ position of cladinose can apparently destroy the inducer property but do not affect the inhibitory properties of the antibiotic. The findings clearly show that inducer and inhibitor activities can be dissociated and are consistent with the concept that distinct binding/receptor sites are utilized for inhibition of ribosome function and induction of resistance.
Cefazaflur, a New Parenteral Cephalosporin: In Vitro Studies
Authors: Counts George W. , Gregory David , Zeleznik Dolores , Turck Marvin
Published: June 2012

Cefazaflur was tested in vitro against 262 strains of bacteria. Inhibitory and bactericidal concentrations were determined with two inoculum sizes of bacterial cells in Mueller-Hinton broth and nutrient broth. Agar dilution studies also were performed. When tested in agar, 5.0 μg or less of cefazaflur per ml inhibited almost all strains of
Staphylococcus aureus, Escherichia coli, Klebsiella
, and
Proteus mirabilis
. The drug was less active against
Enterobacter
and indole-positive
Proteus
, and 7.5 μg of antibiotic per ml inhibited approximately two-thirds to one-fourth of the strains. A concentration of 50 μg of cefazaflur per ml was required for inhibition of the enterococci. There was negligible activity against
Pseudomonas
. The drug demonstrated less activity in broth than in agar, and a major inoculum effect was seen with some strains. For example, with a lower inoculum, 2.5 μg of cefazaflur per ml killed all strains of
E. coli
, whereas with the higher inoculum, 7.5 μg of cefazaflur per ml, inhibited 64% and killed only 8% of strains. The activity of the drug for some strains was greater in Mueller-Hinton broth; for others, it was greater in nutrient broth. There were considerable differences in the results of the broth and agar studies for some species when the same medium was employed. Because of differences in activity found with different media, inocula, and method of testing, an evaluation of the eventual usefulness of cefazaflur must await the results of in vivo studies.
Distribution of Sodium Cefazolin in Serum, Muscle, Bone Marrow, and Bone of Normal Rabbits
Authors: Pitkin D. H. , Sachs C. , Zajac I. , Actor P.
Published: June 2012

Cefazolin levels were detected in bone and bone marrow of normal rabbits dosed intramuscularly, even in the absence of detectable levels in serum.
Efficacy of 5,6-Dihydro-5-Azathymidine Against Cutaneous Herpes Simplex Virus in Hairless Mice
Authors: Underwood Gerald E. , Weed Sheldon D.
Published: June 2012

5,6-Dihydro-5-azathymidine, administered subcutaneously, was active both prophylactically and therapeutically against cutaneous herpesvirus infection of hairless mice. Activity was comparable to that obtained with adenine arabinoside.
Gas Chromatographic Determination of 5-Fluorocytosine: a Modified Extraction Method
Authors: Wee Siok-Hui , Anhalt John P.
Published: June 2012

A modified procedure for the gas-chromatographic determination of 5-fluorocytosine in serum is described. A more volatile solvent mixture for extraction is used to reduce sample preparation time before chromatography. Comparison of values from assay of 12 serum samples by our method and the reference method gave a correlation coefficient of 0.99.
Absorption of Orally Administered Nafcillin in Normal Healthy Volunteers
Authors: Watanakunakorn Chatrchai
Published: June 2012

The absorption of orally administered nafcillin sodium monohydrate buffered with calcium carbonate was studied in 10 healthy human volunteers. Dosages of 500 mg and 1 g were studied in fasting and nonfasting states. There was considerable individual variation in the absorption of nafcillin, although measurable serum concentrations were obtained in all subjects. With few exceptions, peak serum concentrations were reached faster and were more predictable in the fasting state than in the nonfasting state. In the majority of subjects, food interfered with nafcillin absorption. Measurable serum concentrations persisted for 4 h in almost all subjects, but there were no or negligible serum concentrations at 6 h. The mean serum concentrations obtained in the present study were higher than those reported in an earlier study.
Bactericidal Activity of Macromomycin, an Antitumor Antibiotic
Authors: Buckmire Francis L. A. , Winkelhake Jeffrey L.
Published: June 2012

Susceptibility testing by the broth dilution method showed that all the gram-positive but only some of the gram-negative bacteria tested were susceptible to the antitumor antibiotic, macromomycin (MCR; NSC 170105). The minimal inhibitory concentration for the susceptible organisms was less than 3 μg/ml. The action of MCR was bactericidal; however, at very high concentrations (50 μg/ml and above) some organisms occasionally escaped death. None of the escaped organisms was resistant to MCR. In combination with other commonly used antibiotics, MCR displayed partial synergy for
Pseudomonas aeruginosa
(from a minimal inhibitory concentration of >100 to 12.5 μg/ml with 100 μg of chloramphenicol per ml) and for
Bacillus pumilus
and
Staphylococcus aureus
(from 1.6 to 0.4 μg/ml and below) with polymyxin B. As with mammalian cells,
125
I-labeled MCR was irreversibly bound to both gram-positive and -negative bacteria. Treatment with trypsin of the
125
I-labeled MCR-exposed cells did not release the bound MCR or reverse its lethal effect. When in solution in a protective buffer at 4°C, MCR was stable for up to 45 days; at 37°C, however, 25% of its bactericidal activity was lost in 72 h. Loss of activity was enhanced 16-fold in the presence of both heated and unheated pooled human sera. Urine had no effect on the activity of MCR.
Uniform Susceptibility of Various Strains of
Coccidioides immitis
to Amphotericin B
Authors: Collins M. S. , Pappagianis D.
Published: June 2012

The susceptibility of 12 strains of
Coccidioides immitis
to amphotericin B (amB) was studied in vitro and in vivo. The minimal inhibitory concentration (MIC) of the mycelial phase of these strains was 0.078 to 0.16 μg/ml after 3 days of incubation, but by 15 days all strains were inhibited by 2.5 μg/ml. Mice infected intraperitoneally with these strains were sucessfully treated with 0.5 mg of amB per kg per day. These strains included several studied by others and which reportedly varied widely in susceptibility (MIC from 0.24 to 24.01 μg/ml) to amB. Four of these strains representing this putative broad range of susceptibility were used to infect mice intranasally. Regardless of infecting strain, mice were sucessfully treated with 0.38, 0.75, and 1.5 mg/kg, but 0.19 mg/kg was only partially effective. Thus, in vivo as well as in vitro there was a uniform response of
C. immitis
strains to amB.
Beta-Lactamase-Directed Barrier for Penicillins of
Escherichia coli
Carrying R Plasmids
Authors: Yamamoto Tatsuo , Yokota Takeshi
Published: June 2012

Strains of
Escherichia coli
and
Salmonella typhimurium
carrying R plasmids, which were obtained from ampicillin-resistant clinical isolates of
E. coli
and
Klebsiella
spp. and specified either the type IIIa (TEM-type) or type Va (oxacillin-hydrolyzing) β-lactamase, are resistant not only to ampicillin but also to carbenicillin and sulbenicillin. The latter two derivatives, however, are poorly hydrolyzed in vitro by the β-lactamases. Although values of

K
m

of the enzymes are lower for sulbenicillin and carbenicillin than for ampicillin, the ratios of

V
max

to

K
m

for sulbenicillin and carbenicillin are not high enough to explain the high resistance in
E. coli
bearing the R plasmid. Two mutants of the plasmids conferring a temperature-sensitive ampicillin resistance were induced by nitrosoguanidine treatment. It was confirmed that
E. coli
CSH2, harboring the mutant plasmid, produces a temperature-sensitive β-lactamase and is resistant only at low temperatures (below 33°C), but not at 42°C, to ampicillin, sulbenicillin, and carbenicillin simultaneously. It is thus concluded that β-lactamase itself is responsible for the mechanism of resistance not only to ampicillin but also to sulbenicillin and carbenicillin, even though the enzyme as determined in cell-free extracts hydrolyzes the latter two drugs poorly. An unknown barrier for sulbenicillin and carbenicillin directed by β-lactamase in
E. coli
strains carrying R (
bla
) plasmids is postulated.
Mercury Resistance and R Plasmids in
Escherichia coli
Isolated from Clinical Lesions in Japan
Authors: Nakahara Hideomi , Ishikawa Tomoaki , Sarai Yasunaga , Kondo Isamu , Kozukue Hiroyuki , Mitsuhashi Susumu
Published: June 2012

The mercury and antibiotic resistance of 338 strains of
Escherichia coli
isolated from hospital patients was determined. Resistance to mercury was found in 58.6% of the isolates. The frequencies of resistance to streptomycin (Sm), tetracycline (Tc), chloramphenicol (Cm), kanamycin (Kan), cephaloridine (Cer), and gentamicin (Gm) were 66.3, 60.3, 56.5, 42.9, 32.1, and 1.5%, respectively. Among the above, 198 mercury- and antibiotic-resistant isolates were selected and tested for their ability to transfer the resistance to susceptible strains of
E. coli
K-12 and
Klebsiella pneumoniae
JK5. R plasmids carrying mercury resistance were demonstrated in 89.9% of the mercury-resistant strains of
E. coli
. Furthermore, R(Hg,Sm,Tc,Cm) plasmids were demonstrated most frequently, followed by R(Hg,Sm,Tc,Cm,Kan), R(Hg,Cm,Kan), and R(Hg,Sm,Tc,Cm,Kan,Cer) plasmids.
In Vitro Evaluation of Three Iodine-Containing Compounds as Antiplaque Agents
Authors: Tanzer J. M. , Slee A. M. , Kamay B. , Scheer E. R.
Published: June 2012

The antibacterial activity of three iodine-containing compounds was determined for strains of four dental plaque-forming microorganisms, using an in vitro preclinical plaque model system. Solutions of inorganic iodine, povidone-iodine, and Wescodyne were tested for antiplaque activity against preformed plaques of a number of strains of
Streptococcus mutans, Streptococcus sanguis, Actinomyces viscosus
, and
Actinomyces naeslundii
. Solutions of inorganic iodine were more effective as antiplaque agents, with respect to minimal bactericidal concentration and time and frequency of treatments, than solutions of Wescodyne and povidone-iodine. Inorganic iodine appeared to be particularly effective against the most cariogenic (
S. mutans
) and periodontopathic (
A. viscosus
) organisms while allowing survival of the least orally pathogenic plaque-forming microorganism (
S. sanguis
). It is suggested that topical application of solutions of inorganic iodine may be useful in controlling dental caries and actinomyces-associated periodontal disease.
Effects of Small-Particle Aerosols of Rimantadine and Ribavirin on Arterial Blood pH and Gas Tensions and Lung Water Content of A2 Influenza-Infected Mice
Authors: Arensman J. B. , Dominik J. W. , Hilmas D. E.
Published: June 2012

The respiratory pathophysiology of A2 influenza infection was studied in mice treated with small-particle aerosols (SPA) of rimantadine or ribavirin. Untreated infections in mice resulted in survival rates of 15% or less and were characterized by (i) severe hypoventilation (decreased P

O
2

and increased P

CO
2

), (ii) compensated respiratory acidosis (increased P

CO
2

and HCO
3
−
, with normal pH), (iii) pneumonia with increased ratio of wet/dry lung weight, and (iv) hypothermia. Treatment with SPA of rimantadine (21 mg/kg per day for 4 days) beginning 72 h after virus challenge significantly improved survival rate (80%) but failed to alter lung pathology from that found in infected, untreated mice. Rimantadine treatment decreased somewhat the severity of hypoventilation, respiratory acidosis, lung wet weight, hypothermia, and lung virus titers from that observed in infected, untreated mice. SPA of ribavirin (26 mg/kg per day for 4 days) initiated 6 h after SPA exposure of mice to virus significantly improved survival rate (95%) and reduced lung virus titers and lung pathology. Gas exchange and pulmonary edema in ribavirin-treated, infected mice were significantly improved over those of infected, untreated controls. The mechanisms for increased survival rates induced by SPA of rimantadine remain uncertain, since increased survival rates could not be ascribed entirely to improvements in lung functions. In contrast, however, ribavirin treatment appeared to improve survival rates by reducing major lung pathology and pulmonary dysfunction. This was probably mediated through the antiviral effects of ribavirin.
Comparison of the Curative Antimalarial Activities and Toxicities of Primaquine and Its
d
and
l
Isomers
Authors: Schmidt L. H. , Alexander Sheila , Allen Linda , Rasco Jane
Published: June 2012

This investigation was undertaken to determine whether either
d
-primaquine or
l
-primaquine has sufficient advantage over primaquine to warrant evaluation for curative activity in human volunteers infected with
Plasmodium vivax
. It was found: (i) that the capacities of the isomers and the racemate to cure infections with
Plasmodium cynomolgi
in rhesus monkeys were essentially identical; (ii) that the subacute toxicities of the isomers and racemate for this monkey were qualitatively the same, but that
l
-primaquine was three to five times as toxic as
d
-primaquine and at least twice as toxic as primaquine; and (iii) that the acute single-dose toxicities of the isomers for mice were not only qualitatively different, but that the
d
isomer was at least four times as toxic as
l
-primaquine. Since previous appraisals of curative activity and tolerability of 8-aminoquinolines in rhesus monkeys have correlated well with appraisals in human volunteers, attention was focused on results acquired with these test subjects. The relevant evaluations showed that
d
-primaquine had a therapeutic index at least twice that of primaquine. If this advantage carries over to man, problems that now complicate routine use of primaquine might be obviated. Therefore, a critical comparison of
d
-primaquine and primaquine in human volunteers seems indicated.
Electrical Impedance Measurements in the Reading and Monitoring of Broth Dilution Susceptibility Tests
Authors: Colvin H. J. , Sherris J. C.
Published: June 2012

Electrical impedance changes in the medium were studied during traditional broth dilution tests. Tests involved clinical isolates of
Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Enterobacter
sp.,
Klebsiella
, and enterococcus and ten antibiotics. Minimal inhibitory concentration (MIC) values from overnight visual readings were compared with MIC values determined from electrical impedance end points, using inocula of 10
6
organisms per ml. Ninety-three percent of the results were within one twofold dilution of each other. When the impedance end point was determined at 6 h, this correlation was lowered to 34%. By increasing the initial electrical impedance inoculum 10-fold, the correlation between the 6-h impedance MIC and the overnight visual MIC was improved to 74%. Ampicillin, tetracycline, and polymyxin E results accounted for most discrepancies. Continuous monitoring of impedance changes suggested that better correspondence could be obtained by adjusting the end point criteria for the 6-h impedance MIC with different antibiotics. Electrical impedance methods for reading bacterial end points in automated clinical laboratory instruments appear promising.
Bactericidal Activity of the Combinations of Gentamicin with Clindamycin or Chloramphenicol Against Species of
Escherichia coli
and
Bacteroides fragilis
Authors: Klastersky Jean , Husson Mireille
Published: June 2012

The bactericidal activity of clindamycin, chloramphenicol, and gentamicin alone and of gentamicin plus clindamycin and gentamicin plus chloramphenicol was studied on 8 strains of
Escherichia coli
and 10 strains of
Bacteroides fragilis
isolated from clinical material. Gentamicin did not interfere with the activity of clindamycin or chloramphenicol against
B. fragilis
. The activity of gentamicin against
E. coli
was not influenced by clindamycin, but chloramphenicol suppressed the rapid bactericidal activity of gentamicin in seven out of eight strains of
E. coli
examined.