bluuebunny/crossref_metadata_2025 huggingface dataset:
Restriction Enzyme Analysis of Plasmids from
Haemophilus influenzae
Authors: Harkess N. K. , Murray M. L.
Published: June 2012

Examination of
Haemophilus influenzae
strains isolated in New Orleans revealed ampicillin-resistant strains with plasmids of size classes not previously detected in North America. The molecular weight of plasmids in five ampicillin-resistant strains ranged from 0.8 × 10
6
daltons (0.8 Mdal) to 36 Mdal. The molecular weights of the plasmids were determined by sucrose gradient centrifugation, electron microscopy, and agarose gel electrophoresis. Plasmids of the previously detected 30-Mdal size class were found in three of the five ampicillin-resistant strains. Restriction enzyme analysis is consistent with a close relationship between these three 30-Mdal plasmids. Of the two remaining ampicillin-resistant strains, one contained a single plasmid of 36 Mdal and the other contained two plasmids of 0.8 and 2.3 Mdal.
Unpredictable Response of
Pseudomonas aeruginosa
to Synergistic Antibiotic Combinations In Vitro
Authors: Heineman Herbert S. , Lofton Wendell M.
Published: June 2012

The combined activity of ticarcillin and each of three aminoglycosides, gentamicin, tobramycin, and amikacin, was studied with 45 clinical isolates of
Pseudomonas aeruginosa
. All strains individually were susceptible to each of these agents. Comparison of the results revealed highly variable interaction, both from strain to strain and from one aminoglycoside to another against the same strain. Against 11 strains, none of three antibiotic pairs tested was synergistic by conventional criteria; against the remaining 34, three, any two, or any one pair among those tested was synergistic. The minimal inhibitory concentrations of individual drugs gave no indication of the degree of synergism to be expected. We conclude that generalizations about the behavior of this organism vis-à-vis penicillin-aminoglycoside combinations in vitro are subject to many exceptions. Furthermore, no test using a particular antibiotic combination is reliable as a screen for other combinations. If this experience is duplicated in vivo, combination testing may be as important for the choice of combination therapy as individual susceptibility testing is for the choice of individual antibiotics.
Pharmacology and Efficacy of Netilmicin
Authors: Trestman Irwin , Parsons James , Santoro Jerome , Goodhart Glenn , Kaye Donald
Published: June 2012

Twenty-six patients, 20 to 77 years of age, were treated with netilmicin, mean dose 2 mg/kg every 8 h intramuscularly or in a 20-min intravenous infusion. The mean serum half-lives in patients with creatinine clearances of ≥90 ml/min and 60 to 90 ml/min were 3.2 and 3.4 h, respectively. In patients with serum creatinines of ≤1.4 mg/100 ml and creatinine clearances of ≥60 ml/min, mean serum levels were 9.0 and 1.2 μg/ml, respectively, 5 to 15 min and 7.5 h post-intravenous infusion, and 7.1 and 1.7 μg/ml, respectively, 1 and 8 h post-intramuscular injection. Twenty-five patients had acute pyelonephritis; 7 of the 25 had bacteremia. The infecting bacteria were
Escherichia coli
(15),
Proteus mirabilis
(5),
Pseudomonas aeruginosa
(2),
Klebsiella pneumoniae
(1),
Enterobacter hafniae
(1), and both
Proteus rettgeri
and
Proteus morganii
(1). All were inhibited by 6.3 μg of netilmicin per ml, except for the
P. rettgeri
, which required 25 μg/ml for inhibition. Of 23 patients who could be evaluated, 19 were bacteriologically and clinically cured at follow-up. Of the remaining four, one relapsed, two became reinfected, and one was lost to follow-up. Five patients developed nephrotoxicity; two of the five had previous renal insufficiency. Three patients, one with abnormal renal function, developed ototoxicity detected only with audiograms. These studies suggest that netilmicin is effective in serious gram-negative bacillary infections, but is nephrotoxic and ototoxic in humans.
Clinical Pharmacology of Cefadroxil in Infants and Children
Authors: Ginsburg Charles M. , McCracken George H. , Clahsen Joan C. , Thomas Marion L.
Published: June 2012

The pharmacokinetics of cefadroxil suspension were studied in 30 children, 13 months to 12 years of age (mean age, 5.7 years). Average peak concentrations in serum of 11 to 14 μg/ml and of 7 to 10 μg/ml after 15- and 10-mg/kg doses, respectively, were not substantially affected by the feeding status. The serum half-life values were 1.3 to 1.5 h. Cefadroxil was detected in saliva of all children 2 h after 15-mg/kg doses: the levels ranged from 0.17 to 2.6 μg/ml (mean, 0.46 μg/ml). The average concentrations in urine were 1,700 and 2,620 μg/ml at 0 to 2 and 2 to 4 h, respectively, after 15-mg/kg doses. In a randomized controlled study of 50 children with impetigo, cefadroxil was as effective as penicillin G in curing existing lesions and in preventing development of new lesions. Cefadroxil may be useful for therapy of mucocutaneous and urinary tract infections in infants and children.
Antibiotic Susceptibility of Clinical Isolates of
Listeria monocytogenes
Authors: Wiggins Geraldine L. , Albritton William L. , Feeley John C.
Published: June 2012

A broth microdilution method was used to measure the minimal inhibitory concentrations (MICs) of the antibiotics most often recommended for treatment of listeriosis. The MICs of ampicillin, penicillin, erythromycin, and tetracycline for 175 strains of
Listeria monocytogenes
were below the approximate MIC breakpoint for susceptible strains as recommended by the National Committee on Clinical Laboratory Standards. Inhibition diameters for 125 strains were measured by the standardized disk method (National Committee on Clinical Laboratory Standards) and compared with the appropriate MIC values. By both methods, strains were susceptible to the above four antibiotics, except for three strains, which were intermediate in susceptibility to penicillin by the disk method. Since the minimal bactericidal concentrations for ampicillin and penicillin significantly exceeded the MICs for these antibiotics, 45 strains were evaluated with ampicillin (5 μg/ml) and gentamicin (1 μg/ml) to compare the synergistic bactericidal effect of the two used in combination and singly. An increased kill of 100-fold was observed with the antibiotics combined in 19 strains after 4 to 6 h and in 40 strains after 24 h. A comparison of results with microdilution in Trypticase soy broth and agar dilution in Mueller-Hinton agar revealed that MICs for gentamicin, kanamycin, and streptomycin were strongly influenced by the media used. The MICs were consistently lower in Mueller-Hinton agar.
Effect of
N
′-Methylnicotinamide on the Renal Accumulation and Reabsorption of Gentamicin in Rats
Authors: Jerauld R. , Silverblatt F. J.
Published: June 2012

N
′-methylnicotinamide, a substrate of the organic base transport system, reduced renal accumulation of [
14
C]gentamicin in rats by 15% and increased clearance by 25%, suggesting that gentamicin is not secreted by this mechanism.
Cerebrospinal Fluid Penetration of Amikacin
Authors: Briedis Dalius J. , Robson Hugh G.
Published: June 2012

Adult volunteers underwent a single lumbar puncture 1 to 8.5 h after one 7.5-mg/kg intramuscular amikacin injection. Eighteen showed no detectable drug in cerebrospinal fluid; six had concentrations <0.5 μg/ml.
Comparison of Cephalothin and Cefamandole Prophylaxis During Insertion of Prosthetic Heart Valves
Authors: Archer Gordon L. , Polk Ron E. , Duma Richard J. , Lower Richard
Published: June 2012

Cefamandole nafate (CM) and cephalothin sodium (CP) were administered as prophylaxis in a randomized, prospective study to 30 consecutive patients undergoing prosthetic cardiac valve insertion. A single dose of 20 mg/kg was given intramuscularly during anesthesia induction, and serial plasma antibiotic concentrations, atrial muscle and cardiac valve tissue antibiotic levels, plasma bactericidal activity against pathogenic staphylococci, and infectious complications were determined and compared for the two drugs. Both antibiotics produced high plasma levels (>20 μg/ml 30 min after injection) which fell less than 25% during the period of cardiopulmonary bypass. However, CM levels were significantly higher at most time periods (
P
<0.05) than CP levels. CP levels were undetectable in atrial muscle from 14 of 15 patients and in valves from 10 of 15 patients. In contrast, CM bioactivity was found in all tissues. Differences in tissue antibiotic concentration could not be accounted for by differences in plasma concentrations or by CP tissue binding and were assumed to be caused by differences in penetration. Plasma bactericidal activity against staphylococci was equal for the two drugs (median titer, 1:16). No infections were seen in either group. CM appeared to be an effective and perhaps preferable prophylactic antibiotic for use during cardiac surgery.
Pharmacology of Cefaclor in Normal Volunteers and Patients with Renal Failure
Authors: Santoro Jerome , Agarwal B. N. , Martinelli Reinaldo , Wenger Norma , Levison Matthew E.
Published: June 2012

After a 500-mg dose of cefaclor, the mean peak plasma level was 12.4 μg/ml and after a 250-mg dose it was 5 μg/ml in normal volunteers. Food intake significantly reduced absorption. Probenecid prolonged plasma levels. Mean plasma half-life in normal volunteers was 0.8 h. Only about 50% of the dose was excreted in the urine within 4 h in normal volunteers. Plasma half-life in patients with renal insufficiency was only about 3 h, which suggests that cefaclor may be eliminated by nonrenal mechanisms in humans. Urinary levels of cefaclor were adequate to inhibit susceptible pathogens even in patients with moderately severe renal failure. Plasma half-life during hemodialysis was 2.1 h and rose to 2.8 h after dialysis.
Pharmacokinetic Comparison of Oral Bacampicillin and Parenteral Ampicillin
Authors: Bergan Tom
Published: June 2012

Bacampicillin is a new oral prodrug which is rapidly converted to ampicillin during absorption from the gastrointestinal tract. High serum peaks of ampicillin are obtained. Bacampicillin orally was compared pharmacokinetically with parenteral ampicillin (intravenously and intramuscularly). A cross-over study on healthy volunteers showed that ampicillin concentrations after equimolar doses of bacampicillin orally and ampicillin intramuscularly were of the same order. The mean of the individual peak values (regardless of time of occurrence) after a dose of 800 mg of bacampicillin was 13.1 ± 3.8 μg/ml. Absorption rates of the two doses were similar, as were their distribution volumes (approximately 25% of the body weight). Bioavailability was 87% for bacampicillin, compared to 71% for ampicillin.
Combination of Pentamidine and Trimethoprim-Sulfamethoxazole in the Therapy of
Pneumocystis carinii
Pneumonia in Rats
Authors: Kluge Ronica M. , Spaulding David M. , Spain Alan J.
Published: June 2012

Treatment with either pentamidine isethionate or trimethoprim-sulfamethoxazole significantly reduces the mortality of
Pneumocystis carinii
pneumonia. It is not known whether a combination might act in an additive, synergistic, or antagonistic manner. We studied the interaction of these two agents in the steroid-conditioned rat model of pneumocystosis. Of animals receiving pentamidine alone, 48% died and 45% had
P. carinii
cysts at autopsy. Trimethoprim-sulfamethoxazole alone resulted in 21% mortality, and cysts were found in 28%. Both agents in full doses resulted in 45% deaths and cysts in 37%. Animals treated with half-dosages of pentamidine plus trimethroprim-sulfamethoxazole had mortality of 35%, and 21% had cysts. Trimethoprim alone, in two dosages, was ineffective in eradicating
P. carinii
cysts. The data suggest that combination therapy is no more effective than trimethoprim-sulfamethoxazole alone in the treatment of
P. carinii
pneumonia.
Excretion of Cefamandole, Cefazolin, and Cephalothin into T-Tube Bile
Authors: Ratzan Kenneth R. , Baker H. Barry , Lauredo I.
Published: June 2012

The biliary tract excretion of cefamandole, cefazolin, and cephalothin was measured in eight patients with T-tubes inserted into their common ducts after ductal exploration for biliary tract stones. Each patient received 1.0 g intravenously of each cephalosporin on 3 separate days; T-tube bile and serum were collected at selected time intervals thereafter. In seven patients, bile and urine were collected for 6 h after the administration of each drug. Mean peak levels of cefamandole, cefazolin, and cephalothin in bile were 352, 46, and 12 μg/ml, respectively. The respective mean peak serum levels were 55.0, 92.8, and 32.4 μg/ml. Despite the fact that peak serum levels of cefazolin were 1.5 times those of cefamandole, levels in bile of cefamandole were about 8 times those of cefazolin. Over a 6-h period, almost three times as much cefamandole was excreted into bile as was cefazolin. Therefore, in those patients with biliary tract sepsis, in whom a cephalosporin is indicated for therapy, cefamandole appears to be the drug of choice.
Sodium Clavulanate Potentiation of Cephalosporin Activity Against Clinical Isolates of Cephalothin-Resistant
Klebsiella pneumoniae
Authors: Jackson Roger T. , Harris LeRoy F. , Alford Robert H.
Published: June 2012

Plasmid-carrying
Klebsiella pneunomiae
clinical isolates with agar dilution minimum inhibitory concentrations (MIC) of 32 μg/ml or greater were tested for in vitro potentiation of cephalothin activity by clavulanic acid (BRL-14151), an inhibitor of beta-lactamases. The addition of 10 μg of clavulanate per ml caused greater than a 500-fold reduction in geometric mean cephalothin agar dilution MIC, with lesser but significant reductions resulting from clavulanate concentrations of 5 or 1 μg/ml. Clavulanate-potentiated reduction of cephalothin MICs in broth against resistant
Klebsiella
were comparable to reduction in agar dilution MICs as a rule. However, a low concentration (1 μg/ml) of clavulanate produced cephalothin MICs in broth several-fold higher than by the agar dilution method. Modest cephalothin-potentiating effects of clavulanate on cephalothin-susceptible strains and on cefoxitin against cephalothin-resistant
Klebsiella
strongly suggested that the major effect of clavulanate was beta-lactamase inhibition.
Antiviral Activity of Extracts from Marine Algae
Authors: Richards James T. , Kern Earl R. , Glasgow Lowell A. , Overall James C. , Deign E. Frank , Hatch Melvin T.
Published: June 2012

Extracts of two species of marine algae,
Constantinea simplex
and
Farlowia mollis
, were tested for antiviral activity in tissue culture and in experimental infections of mice. Treatment of confluent mouse embryo fibroblast cell monolayers with either compound before viral inoculation was effective in inhibiting the replication of herpes simplex virus type 1 and type 2, vaccinia virus, and vesicular stomatitis virus, but not encephalomyocarditis virus, Semliki Forest virus, or murine cytomegalovirus. Prophylactic administration of these extracts was effective in reducing final mortality or prolonging the mean day of death of animals inoculated by the intraperitoneal, intracerebral, or intranasal routes with herpes simplex virus type 2. When therapy was initiated after viral inoculation or at a site other than that of viral inoculation, no significant effect on mortality or on mean day of death was observed. Neither preparation was effective in mice inoculated intraperitoneally with encephalomyocarditis virus, Semliki Forest virus, or murine cytomegalovirus or in animals infected intravaginally with herpes simplex virus type 2. The prophylactic but not therapeutic antiviral activity of these preparations seriously limits their potential use in human herpes simplex virus infections.
In Vitro Studies with Sch 21420 and Sch 22591: Activity in Comparison with Six Other Aminoglycosides and Synergy with Penicillin Against Enterococci
Authors: Sanders Christine C. , Sanders W. Eugene , Goering Richard V.
Published: June 2012

In vitro tests were performed with Sch 21420 and Sch 22591 to determine (i) their activity in comparison to six other aminoglycosides against 343 clinical isolates, and (ii) whether synergy with penicillin G could be demonstrated with enterococci. In broth dilution tests, Sch 22591 was more active than the seven other aminoglycosides against
Staphylococcus aureus, Enterobacteriaceae
, and most nonfermenting gram-negative bacilli. Sch 22591 was as active as tobramycin against
Pseudomonas aeruginosa
. The activity of Sch 21420 was comparable to gentamicin, sisomicin, netilmicin, and tobramycin but greater than amikacin or kanamycin against
S. aureus
and most genera of
Enterobacteriaceae
. Sch 21420, amikacin, and kanamycin were (i) more active than the other five aminoglycosides against
Proteus rettgeri
and
Providencia stuartii
, but (ii) less active than the other five aminoglycosides against
Neisseria gonorrhoeae
, enterococci, most nonfermenting gram-negative bacilli,
Proteus mirabilis
, and
Proteus morganii
. Studies on the bactericidal activity of Sch 22591 with penicillin indicated a synergistic interaction against enterococci, including strains highly resistant to streptomycin and kanamycin. This could be demonstrated with combinations containing 3.0 to 6.0 μg of Sch 22591 per ml and was comparable to that observed with penicillin/gentamicin. Penicillin plus Sch 21420 (25 μg/ml) also demonstrated synergy against enterococci, including strains highly resistant to streptomycin. However, synergy did not occur against strains highly resistant to kanamycin. These latter results were similar to those obtained in tests with penicillin/kanamycin.
Two Transport Systems for Tetracycline in Sensitive
Escherichia coli
: Critical Role for an Initial Rapid Uptake System Insensitive to Energy Inhibitors
Authors: McMurry Laura , Levy Stuart B.
Published: June 2012

Escherichia coli
sensitivity to tetracycline involves transport and accumulation of the antibiotic within the cell by two different uptake systems: an initial rapid uptake, which occurs over the initial 6 min of contact of the cell with tetracycline, and a slower uptake system, which continues indefinitely and whose rate of uptake is 1/10 that of the rapid system. Only the slow uptake system is blocked by inhibitors of energy-driven systems; it appears to be particularly dependent upon energy from oxidative phosphorylation. Although both uptake systems lead to accumulation of intracellular tetracycline and contribute to the cell's sensitivity, the rapid uptake system appears to be the more important. While these studies confirm active transport of tetracycline into the cell, they demonstrate that a critical uptake system which appears insensitive to metabolic inhibitors occurs initially.
Effect of a Staphylococcin on
Neisseria gonorrhoeae
Authors: Morriss Dorothy M. , Lawson John W. , Rogolsky Marvin
Published: June 2012

Phage group 2 staphylococcal strain UT0002 contains a large 56S virulence plasmid with genes that code for both exfoliative toxin and a specific staphylococcin termed Bac R
1
. Four penicillinase-producing strains and three penicillin-susceptible strains of
Neisseria gonorrhoeae
were killed by Bac R
1
. After 30 min of growth of the penicillin-resistant TR1 strain in 62.5 arbitrary units of Bac R
1
per ml, loss of viability was approximately 90%, and, after 5 h, an approximately 99.99% loss of viability was observed. Lysis did not accompany cell death, and 84% of the Bac R
1
added to the growth medium was adsorbed to the gonococcal cells. The extracellular supernatant fluid from a substrain of staphylococcal strain UT0002 cured of the plasmid for Bac R
1
production had no lethal effect on the gonococcal strains. Bac R
1
was also shown to have bactericidal activity against an L-form of
N. meningitidis
, indicating that the outer envelope of a neisserial cell is not needed for bacteriocin activity. Ten different normal human sera were unable to neutralize Bac R
1
activity. The bacteriocin lacks adsorption specificity. It binds to but does not kill
Escherichia coli
cells, indicating that the cell envelope of gram-negative organisms can provide protection against the staphylococcin.
Modified Peptidoglycan Transpeptidase Activity in a Carbenicillin-Resistant Mutant of
Pseudomonas aeruginosa
18s
Authors: Curtis Nigel A. C. , Brown Carol , Boxall Mike , Boulton Mike G.
Published: June 2012

A carbenicillin-resistant mutant of
Pseudomonas aeruginosa
18s was found to possess peptidoglycan transpeptidase activity significantly more resistant to inhibition by benzyl penicillin, ampicillin, carbenicillin, and cephaloridine than that of the parent strain. The mutant was more resistant than the parent strain to all of the β-lactam antibiotics tested, and 50% inhibition values for these compounds against membrane-bound model transpeptidase activity paralleled this increase. The resistance of the mutant to kanamycin, streptomycin, and chloramphenicol was unchanged.
Inhibition of Cell Division of
Escherichia coli
by a New Synthetic Penicillin, Piperacillin
Authors: Iida Kyoko , Hirata Seiichi , Nakamuta Seiichi , Koike Masaatsu
Published: June 2012

The mechanism of the action of piperacillin against
Escherichia coli
was investigated. This drug converted cells to filaments, but did not show lytic action in a range of concentrations below 25 μg/ml. In some of the filaments, stretched constrictions with various diameters were observed. Addition of piperacillin to a synchronous culture inhibited cell division immediately at any stage of the cell cycle. The results of morphological examination of synchronous cultures show that the percentage of filaments with a stretched constriction corresponds to that of normally septated cells before addition of the drug. Furthermore, peptidoglycan synthesis and cross-linking were not inhibited by this drug. It is likely that this drug inhibits only septum formation, but not the growth of wall, and that stretched constrictions are a result of longitudinal growth of septation caused by the drug. Examination of affinity of the drug to penicillin-binding proteins shows that protein 3 is the most sensitive, proteins 2 and 7 are moderately so, and protein 1 is sensitive only to high concentrations of the drug.
Vacuolization in Cultured Cells Induced by Amphotericin B
Authors: Lundgren E. , Roos G.
Published: June 2012

Amphotericin B induced vacuoles in one HeLa cell line and in some unrelated cell lines. Cell growth was not affected.
Recovery from Aminoglycoside Nephrotoxicity with Continued Drug Administration
Authors: Luft Friedrich C. , Rankin Laura I. , Sloan Rebecca S. , Yum Moo Nahm
Published: June 2012

To examine the nephrotoxicity of prolonged gentamicin administration compared to the effect obtained when a less toxic aminoglycoside is substituted during the course of treatment, we gave gentamicin (67.5 mg/kg per day) to rats for 21 days, gentamicin for 14 days followed by either netilmicin or tobramycin for 7 days, or gentamicin for 14 days followed by saline diluent. After initial tubular, necrosis, the animals recovered from renal injury whether the drug was continued or discontinued or another drug was substituted. These data are consistent with the observation that regenerating renal epithelium is resistant to continued or additional nephrotoxic insults. These findings suggest that improvement in renal function during aminoglycoside therapy cannot necessarily be attributed to the substitution of another aminoglycoside or other therapeutic interventions.
Pharmacokinetics of Azlocillin in Persons with Normal and Impaired Renal Functions
Authors: Fiegel P. , Becker K.
Published: June 2012

The pharmacokinetics of azlocillin, a new wide-spectrum antibiotic of the
N
-substituted group of ureidomethyl penicillins, was investigated in 10 subjects with normal and in 32 subjects with impaired renal functions. After intravenous injection of 2 g of azlocillin, serum concentrations of drug were measured microbiologically. The half-lives of azlocillin were 47 ± 8.8 min in patients with normal renal function, and 293.3 min in patients with severely impaired renal function. The correlation of half-life to renal functions is shown by the equation:
t
/2 = 425.03·Cl
In
−0.4509
, where Cl
In
is inulin clearance. The volume of distribution of the azlocillin was 17.7% of the body weight. Protein binding was similar in patients with normal renal function and in those with severely impaired renal functions. The urinary excretion rate of azlocillin in patients with normal renal function was 64.8 ± 8.8% in 24 h.
Phosphonoacetic Acid in the Treatment of Simian Varicella
Authors: Felsenfeld A. D. , Abee C. R. , Gerone P. J. , Soike K. F. , Williams S. R.
Published: June 2012

Phosphonoacetic acid inhibited replication of simian varicella virus (Delta herpesvirus) in tissue culture. The drug was tested in patas monkeys 40 h after infection with Delta herpesvirus. A total of 200 mg/kg per day was given intramuscularly, divided into two doses every day for a total of 10 days. The treated monkeys were protected from clinical illness, and Delta herpesvirus was not recovered from their lymphocytes. Complement-fixing and neutralizing antibody titers were significantly lower in phosphonoacetic acid-treated monkeys than in the untreated controls. In animals given the drug alone, there was dermatitis and blackening of the skin and hair, serum glutamic oxalacetic transaminase and serum glutamic pyruvic transaminase enzymes were significantly increased, and liver biopsy revealed diffuse cytoplasmic swelling and granulation of the hepatocytes. The therapeutic range of this drug should be studied carefully before considering its use in severe varicella-zoster infection in humans.
CP-45,899, a Beta-Lactamase Inhibitor That Extends the Antibacterial Spectrum of Beta-Lactams: Initial Bacteriological Characterization
Authors: English Arthur R. , Retsema James A. , Girard Arthur E. , Lynch John E. , Barth Wayne E.
Published: June 2012

CP-45,899 {3,3-dimethyl-7-oxo-4-thia-1-azabicyclo(3.2.0)heptane-2-carboxylic acid, 4,4-dioxide, [2S-(2α,5α)]} is an irreversible inhibitor of several bacterial penicillinases and cephalosporinases. In the presence of low concentrations of CP-45,899, ampicillin and other β-lactams readily inhibit the growth of a variety of resistant bacteria that contain β-lactamases. CP-45,899 used alone displays only weak antibacterial activity, with the notable exception of its potent effects on susceptible and resistant strains of
Neisseria gonorrhoeae
. CP-45,899 appears to be somewhat less potent but markedly more stable (in aqueous solution) than the recently described β-lactamase inhibitor clavulanic acid. The spectrum extensions provided by the two compounds are similar. A 1:1 mixture of CP-45,899 and ampicillin displays marked antimicrobial activity in mice experimentally infected with ampicillin-resistant
Staphylococcus aureus, Haemophilus influenzae, Klebsiella pneumoniae
, and
Proteus vulgaris
.
Flavobacterium meningosepticum
Meningitis: Report of Selected Aspects
Authors: Rios Israel , Klimek Joseph J. , Maderazo Eufronio , Quintiliani Richard
Published: June 2012

Two patients developed meningitis due to
Flavobacterium meningosepticum
. Because of resistance to most available antimicrobial agents, intravenous and intraventricular erythromycin was administered to one patient. Subsequent development of resistance to erythromycin prompted the use of intravenous and intraventricular rifamycin, which eventually resulted in cure. Diagnosis of
F. meningosepticum
meningitis in the second patient was delayed, and appropriate therapy was not administered until 4 days prior to the patient's death. Of 82 previously published cases, only 4 occurred in adults. Therapy of meningitis due to this organism has been a difficult problem, and we suggest possible modes of therapy, based on our experience and a review of the literature.
Nafcillin Therapy for
Staphylococcus aureus
Endocarditis
Authors: Masur Henry , Murray Henry W. , Roberts Richard B.
Published: June 2012

Semisynthetic penicillinase-resistant penicillins are recommended for therapy of
Staphylococcus aureus
endocarditis, but evaluation of the efficacy and safety of individual agents has received little attention. At The New York Hospital, 11 heroin addicts and 5 nonaddicts were treated with nafcillin. The 11 addicts did well clinically, but four of the five nonaddicts had severe complications, and three of them died. Important adverse reactions to nafcillin occurred in two patients: one developed leukopenia, and one developed an extensive rash. Methicillin was employed to treat two heroin addicts and four nonaddicts. Five of the six patients were cured bacteriologically, but three patients developed nephritis and one patient developed an extensive rash. Nafcillin appears to be highly efficacious for the treatment of
S. aureus
endocarditis, yielding results at least equal to those obtained with other drugs. Because adverse reactions appear to occur more frequently with methicillin than with nafcillin, we regard nafcillin as the preferable penicillinase-resistant penicillin for the treatment of
S. aureus
endocarditis.
Safety of Oral Vancomycin in Functionally Anephric Patients
Authors: Bryan Charles S. , White Wain L.
Published: June 2012

Administration of a vancomycin oral solution, 2 g daily for 16 days, to functionally anephric patients without inflammatory bowel disease resulted in assayable but low (≤0.66 μg/ml) serum levels in two of the five volunteers.
Susceptibility of the Anaerobic Bacteria, Group D Streptococci,
Enterobacteriaceae
, and
Pseudomonas
to Semisynthetic Penicillins: Carbenicillin, Piperacillin, and Ticarcillin
Authors: Monif Gilles R. G. , Clark Penelope R. , Shuster John J. , Baer Herman
Published: June 2012

Sodium piperacillin T-1220, a new semisynthetic penicillin, was tested in vitro against 297 clinical isolates of anaerobic bacteria and 669 aerobic bacteria by the conventional agar dilution method and compared with carbenicillin and ticarcillin. At a 100-μg/ml concentration the three drugs showed comparable effectiveness against the anaerobes tested. However, at 20 μg/ml, piperacillin was the most effective drug against
Bacteroides fragilis
, peptostreptococci, and group D streptococci. At this drug concentration only 48% of the
B. fragilis
strains exhibited susceptibility to carbenicillin only, 64% exhibited susceptibility to ticarcillin but 90% exhibited susceptibility to piperacillin. Similar findings were observed with peptostreptococci and group D streptococci. On a weight basis piperacillin was statistically shown to be the most effective antibiotic of the three tested against these anaerobes. At 20 μg/ml, piperacillin exhibited a statistically significant difference (
P
< 0.01) over carbenicillin and ticarcillin for
Serratia marcescens, Escherichia coli, Klebsiella
species,
Klebsiella pneumoniae, Pseudomonas
isolates, and
Citrobacter diversus
. At both 20- and 100-μg/ml concentrations, piperacillin appeared to be the most effective (calculated
P
< 0.01) upon
Klebsiella
species,
K. pneumoniae, S. marcescens
, and
C. freundii
in activity over ticarcillin and carbenicillin.
Clavulanic Acid, a Novel Inhibitor of β-Lactamases
Authors: Neu Harold C. , Fu Kwung P.
Published: June 2012

Clavulanic acid, Z-(2R,5R)-3-(β-hydroxyethylidene)-7-oxo-4-oxa-1-azabicyclo-[3,2,0] heptane-2-carboxylic acid, has been shown to be an effective inhibitor of the β-lactamases of the Richmond types II, III, IV, and V. Inhibition is a time-dependent reaction and is irreversible. Clavulanic acid had poor antibacterial activity against
Staphylococcus aureus, Enterobacteriaceae
, and
Pseudomonas aeruginosa
, with minimal inhibitory levels greater than 25 μg/ml. It did inhibit the majority of
Neisseria gonorrhoeae
at 0.1 μg/ml and
Haemophilus influenzae
at 6.3 μg/ml. Clavulanic acid acted synergistically with penicillins and cephalosporins to inhibit β-lactamase-producing
S. aureus
and
Enterobacteriaceae
. Clavulanic acid combined with ampicillin inhibited β-lactamase-producing
N. gonorrhoeae, H. influenzae, Escherichia coli, Salmonella typhi
, and
Shigella sonnei
.
Beta-Lactamase Production and Resistance to Beta-Lactam Antibiotics in
Nocardia
Authors: Wallace Richard J. , Vance Paula , Weissfeld Alice , Martin R. Russell
Published: June 2012

Although ampicillin has been suggested as a useful agent for the treatment of nocardiosis in man, little is known regarding the presence of beta-lactamase in
Nocardia
or its possible role in determining resistance to ampicillin and the other beta-lactam antibiotics. We have evaluated 55 isolates of
Nocardia
for susceptibility to five beta-lactam antibiotics and for the presence of beta-lactamase.
Nocardia
were resistant to penicillin G, cloxacillin, and cefazolin, but 27 and 62% were susceptible to 3.1 and 25 μg of ampicillin per ml, respectively. Almost 90% of these ampicillin-susceptible or intermediate strains were also susceptible to carbenicillin. The combination of ampicillin and cloxacillin was synergistic against many ampicillin-resistant strains. Beta-lactamase was detected in 89% of
Nocardia
isolates when intact cells were used and in six of six strains after cell fractionation. This beta-lactamase was most active against penicillin G and ampicillin, with lesser activity against carbenicillin and cephaloridine. These studies suggest that beta-lactamase may be present in all clinical isolates of
Nocardia
and that mechanisms of antimicrobial resistance other than or in addition to beta-lactamase are responsible for resistance of
Nocardia
to ampicillin and carbenicillin.
HR 756, the
syn
Isomer of a New Methoxyimino Cephalosporin with Unusual Antibacterial Activity
Authors: Chabbert Yves A. , Lutz André J.
Published: June 2012

HR 756, the
syn
derivative of 7-[(2-(2-amino-4-thiazolyl)-2-methoxyimino)acetamido]cephalosporanic acid, is a new semisynthetic cephalosporin. It was 80 times more active than the
anti
derivative against β-lactamase-producing strains of gram-negative bacteria. The range of inhibitory concentrations of HR 756 against gram-negative bacteria, including
Haemophilus influenzae
, susceptible or resistant to penicillins and cephalosporins was from 0.01 to 0.1 μg/ml. This activity was consistently higher than those observed with cephalothin, cephaloridine, cephalexin, and cefazolin. Nevertheless, some strains of
Enterobacter cloacae
were resistant. HR 756 showed very similar activity to that of ampicillin against group A streptococci and
Streptococcus pneumoniae
.
New Cephamycin Antibiotic, CS-1170: Binding Affinity to Penicillin-Binding Proteins and Inhibition of Peptidoglycan Cross-Linking Reactions in
Escherichia coli
Authors: Ohya Satoshi , Yamazaki Mitsuo , Sugawara Shinichi , Tamaki Shigeo , Matsuhashi Michio
Published: June 2012

The binding activity of CS-1170, a new cephamycin antibiotic, to penicillin-binding proteins (PBPs) in
Escherichia coli
and
Proteus
species and the potency of this antibiotic in vitro to inhibit enzymes involved in peptidoglycan cross-linking in
E. coli
were tested. Similar experiments were carried out with the 7α-H analog of CS-1170, R-45656, and the results were compared with those obtained with CS-1170. CS-1170 showed high affinities (compared with that of penicillin G) for
E. coli
PBP-1A, -1Bs, and -3, the PBPs of higher molecular weight, but not PBP-2. It also inhibited the in vitro peptidoglycan cross linking reaction and concomitant release of
d
-alanine at very low concentrations (approximately its minimal inhibitory concentration). This antibiotic also showed very high affinity for PBP-4, -5, and -6, the PBPs of lower molecular weight, and at extremely low concentrations it inhibited
d
-alanine carboxypeptidases IA and IB, corresponding to PBP-5/6 and PBP-4, respectively. CS-1170 seemed to be resistant to the β-lactamase activity of PBP-5 and -6 in
E. coli
and
Proteus
species. R-45656 showed as high an affinity for PBP-1A, -1Bs, and -3 as CS-1170, but unlike CS-1170, it had low affinities for PBP-4, -5, and -6. The concentrations of R-45656 required for inhibition of
d
-alanine carboxypeptidases IA and IB were also much higher than those of CS-1170. R-45656 showed rather low activities in inhibiting the in vitro cross-linking reaction of peptidoglycan and concomitant release of
d
-alanine. Synergism was observed in 9 of 22 strains examined between CS-1170 and mecillinam, which bound specifically to PBP-2.
New Rapid Bioassay of Gentamicin Based on Luciferase Assay of Extracellular ATP in Bacterial Cultures
Authors: Nilsson Lennart
Published: June 2012

Bacterial ATP levels in
Escherichia coli
cultures were determined by luciferin/luciferase assay. Rapid effects of gentamicin on ATP levels in the cultures were studied, and a dose-dependent accumulation of extracellular ATP was demonstrated. This phenomenon was used to develop a rapid bioassay of gentamicin in clinical serum specimens. The accuracy of the assay, expressed as coefficient of variation over the range 16 to 1 μg/ml, varied between 1.8 and 6.5%, compared to 2.3 to 4.7% for an agar disk diffusion assay. Serum gentamicin concentrations were determined by both methods in 122 serum specimens from 43 patients receiving gentamicin alone or in combination with other antibiotics, and the results were compared (
r
= 0.942). Determination of gentamicin based on luciferase assay of extracellular ATP in bacterial cultures requires only 10 μl of serum, allowing for capillary sampling, and results are available within 2 h.
Pharmacokinetics and Safety of Cefamandole in Infants and Children
Authors: Chang Chia T. , Khan Abdul J. , Agbayani Melanie M. , Jhaveri Ramesh , Amin Irfan , Evans Hugh E.
Published: June 2012

Cefamandole, a new cephalosporin antibiotic, has greater activity against common pathogens, including
Escherichia coli, Haemophilus influenzae
, and
Proteus
(including indole-positive strains), than available cephalosporin drugs. We have evaluated the safety and pharmacokinetics of this drug in 30 infants and children. Blood levels and urinary excretion of the drug were similar to those previously found in adults. The only side effects were mild and transient elevation of serum glutamic oxalacetic transaminase in 12 patients and of blood urea nitrogen in 1 patient in whom serum creatinine remained normal and unchanged.
Use of Cefoxitin, New Cephalosporin-Like Antibiotic, in the Treatment of Aerobic and Anaerobic Infections
Authors: Nair S. Ramachandran , Cherubin Charles E.
Published: June 2012

Forty-two patients were treated with intravenous cefoxitin, a new cephamycin antibiotic. These patients had postoperative abdominal sepsis (26), intrathoracic infections (6), urinary tract infections (5), gram-negative bacterial meningitis (2), septic arthritis (1), epidural abscess (1) and isolated septicemia (1). The antibacterial spectrum of cefoxitin was found to be one which included all gram-positive organisms except enterococci, most gram-negative organisms except
Pseudomonas aeruginosa
, and almost all of the important anaerobic organisms. The only five treatment failures included one patient with empyema and one with septic arthritis, both caused by
Serratia marcescens
, initially only moderately susceptible to cefoxitin, which subsequently developed increased resistance, two patients with contaminated intravenous catheters, and one patient with epidural abscess and cerebritis, who was treated late in the course. There was one serious clinical superinfection with
P. aeruginosa
. The drug levels noted in the pus and joint fluid were half to two-thirds of the simultaneous serum level. In inflamed meninges, up to 30% of the serum level was noted in the cerebrospinal fluid, and as the process resolved, 10 to 15% was noted. Toxicity of cefoxitin was mild and constituted skin rash in three patients (7%) and phlebitis in eight (19%).
Penetration of Amoxicillin into Cerebrospinal Fluid
Authors: Strausbaugh Larry J. , Girgis Nabil I. , Mikhail Isis A. , Edman David C. , Miner Walter F. , Yassin Mohamed W.
Published: June 2012

The penetration of amoxicillin into cerebrospinal fluid (CFS) in the presence of meningeal inflammation was evaluated in patients with tuberculous meningitis. Serum and CSF concentrations of amoxicillin were measured at 2 h in nine patients who received a 1-g oral dose and at 1.5 and 4 h in ten patients who received a 2-g intravenous injection of sodium amoxicillin. After the oral dose, CSF concentrations ranged from 0.1 to 1.5 μg/ml. After the intravenous injection, CSF concentrations ranged from 2.9 to 40.0 μg/ml at 1.5 h and from 2.6 to 27.0 μg/ml at 4 h. These data on penetration suggest that parenterally administered sodium amoxicillin may be of value in the therapy of acute bacterial meningitis.
Anaerobic Resistance of Clinical Isolates of
Staphylococcus aureus
to Aminoglycosides
Authors: Harrell Lizzie J. , Evans James B.
Published: June 2012

The anaerobic minimum inhibitory concentration of six aminoglycosides (amikacin, gentamicin, kanamycin, netilmicin, sisomicin, and tobramycin) averaged over 10-fold greater than the aerobic minimum inhibitory concentration for 50 clinical isolates of
Staphylococcus aureus
. Cultures from osteomyelitis and blood generally showed a somewhat greater increase in minimum inhibitory concentration due to anaerobiosis than did cultures from abscesses and wounds, and amikacin activity was most affected by anaerobiosis.
Cell Killing by Simian Virus 40: Protective Effect of Chloroquine
Authors: Norkin Leonard C. , Einck Katie H.
Published: June 2012

Treatment of CV-1 cells with chloroquine before infection by simian virus 40 resulted in the accumulation of fewer nonviable, trypan blue-stainable cells at 72 h. The drug did not affect the fraction of infected T-antigen-producing cells or the viral yields. It did diminish the apparent redistribution of lysosomal
N
-acetyl-β-glucosaminidase from a particulate to a soluble cell fraction, and it caused an increase in the size and number of lysosomes.
Intravenous Use of Cephradine and Cefazolin Against Serious Infections
Authors: Caloza Dionisio L. , Semar Richard W. , Bernfeld Gerald E.
Published: June 2012

The relative efficacy and safety of cephradine and cefazolin were compared in 180 patients with a variety of serious infections caused by susceptible organisms. The patients were randomly assigned to one of two groups of 90 patients each. Most patients received 2 to 4 g per day, administered by intravenous injection in four equally divided doses, for a minimum of 4 days. Based on the clinical and microbiological results, the two cephalosporins were found to be comparable in therapeutic effectiveness. Toxicity was not a problem with either drug.
Enveloped Virus Inactivation by Fatty Acid Derivatives
Authors: Sands J. A. , Landin P. , Auperin D. , Reinhardt A.
Published: June 2012

The enveloped bacteriophage φ6 has been shown to be a valuable model system for the preliminary screening of compounds that might be expected to inactivate herpes simplex virus and other enveloped mammalian viruses. A variety of fatty acid derivatives that form fluid micelles in aqueous media have been found to be potent inactivators of φ6. The chemical nature of the polar head group, the length of the alkyl chain(s), and the extent and geometry of unsaturation are all important parameters in determining the antiviral effectiveness of this class of compounds.
Susceptibility of Gram-Negative Aerobic Bacilli Resistant to Carbenicillin in a General Hospital to Piperacillin and Ticarcillin
Authors: McGowan John E. , Terry Pamela M.
Published: June 2012

During an 8-month period, 858 gram-negative aerobic rods resistant to carbenicillin (minimum inhibitory concentration, ≥128 μg/ml) were isolated. Susceptibility testing of 233 of these suggested that piperacillin might be active against more of these organisms than would carbenicillin or ticarcillin.
Activity of 2,4-Diaminoquinazoline Compounds against
Candida
species
Authors: Castaldo Robert A. , Gump Dieter W. , McCormack John J.
Published: June 2012

Forty recent clinical isolates of three different
Candida
sp. were tested in the microtiter system for susceptibility to two new 2,4-diaminoquinazoline (DAQ) compounds, amphotericin B and flucytosine. The two DAQ preparations showed activity similar to amphotericin B and flucytosine. The geometric mean minimal inhibitory concentrations for these four drugs were as follows: DAQ 1A, 0.64 μg/ml; DAQ 2A, 1.39 μg/ml; amphotericin B, 1.03 μg/ml; and flucytosine, 0.72 μg/ml. An additional seven DAQ compounds were tested but showed less or no activity against 17
Candida
isolates. Forty-eight-hour viability studies with DAQ 2A alone or in combination with amphotericin B, flucytosine, or sulfamethoxazole were carried out with one isolate of intermediate susceptibility to each of these agents except sulfamethoxazole. For this isolate the combination of DAQ 2A and sulfamethoxazole was synergistic, and the combination of DAQ 2A and AMB was either synergistic or additive, whereas the combination of DAQ 2A and flucytosine was antagonistic. Although regrowth of cultures exposed to DAQ 2A was noted over a 48-h period, neither degradation of the drug nor development of resistance to the drug could be detected. Swiss white mice receiving DAQ 1A at a dose of 6 mg/kg for 5 days showed no obvious signs of toxicity, including weight loss.
Investigations of the Occurrence of Gentamicin-Resistant
Staphylococcus aureus
Authors: Buckwold Frederick J. , Albritton William L. , Ronald Allan R. , Lertzman Joy , Henriksen Ruby
Published: June 2012

During the 19-month period from June 1976 to December 1977, 90 patients became colonized or infected with gentamicin-resistant
Staphylococcus aureus
(GRS). Of 63 adults, 56 had hospital-acquired GRS, whereas only 9 of 27 children had hospital-acquired GRS (
P
< 0.001). The other 7 adults and 18 children had GRS present on admission. More than half of those who acquired GRS in the hospital had received prior aminoglycoside therapy. Attack rates were higher in adults than in children and significantly higher on the plastic surgery service than on any other adult service. Phage typing revealed a single-strain outbreak on the plastic surgery ward involving 11 patients, whereas other isolates were of several phage types. Community-acquired GRS occurred more frequently in rural native communities (
P
< 0.02) and may be related to the use of topical gentamicin. Of 17 native children, 10 were from the same area but there was no common phage type. Agar dilution minimal inhibitory concentration (MIC) testing confirmed that all isolates were gentamicin resistant (MIC ≥ 8 μg/ml) and almost all were tobramycin resistant (MIC ≥ 8 μg/ml). Although the MIC distribution between gentamicin disk-susceptible and -resistant strains was significantly different, MIC's for 90% of gentamicin disk-resistant strains were ≤8 μg of amikacin per ml, and MIC's for 92% of the strains were ≤4 μg of netilmicin per ml.
Activity of Antitumor Drugs Against African Trypanosomes
Authors: Kinnamon Kenneth E. , Steck Edgar A. , Rane Dora S.
Published: June 2012

Of 49 compounds known to have antitumor properties, 6 were found to have significant activity against
Trypanosoma rhodesiense
infections in mice. Activity against the African trypanosomes has not been reported previously for any of these six compounds. In order of decreasing activity these compounds were: (i) imidazole-4-carboxamide, 5-(3,3-dimethyl-1,1-triazene), (ii) inosine diglycolaldehyde, (iii)
cis
-diamminedichloro-platinum, (iv) streptozotocin, (v) coralyne sulfate, and (vi) 5-fluoro-2′-deoxyuridine. The percentage of “hits” (12.2%) from these known antitumor agents was approximately twice as great as when other means are employed for the selection of compounds for this test system.