bluuebunny/crossref_metadata_2025 huggingface dataset:
Hospital Isolates of
Serratia marcescens
Transferring Ampicillin, Carbenicillin, and Gentamicin Resistance to Other Gram-Negative Bacteria Including
Pseudomonas aeruginosa
Authors: Olexy Vera M. , Bird Thomas J. , Grieble Hans G. , Farrand Stephen K.
Published: June 2012

Thirteen independent isolates of
Serratia marcescens
associated with nosocomial urinary tract infections were obtained from the clinical microbiology laboratory at Hines Veterans Administration Hospital. The isolates were resistant to at least ampicillin, carbenicillin, gentamicin, and tobramycin. They could be divided into two groups on the basis of their antibiotypes. Group I (9 strains) showed resistance to 13 antibiotics, including 3 beta-lactams, 6 aminoglycosides, tetracycline, sulfonamide, trimethoprim, and polymyxin B. Group II (4 strains) was resistant to 11 antibiotics, including 3 beta-lactams, 5 aminoglycosides, sulfonamide, trimethoprim, and polymyxin B. Donors from both groups transferred resistance traits to
Escherichia coli
. Transconjugants from matings with group II donors all acquired resistance to nine antibiotics, including the three beta-lactams, five aminoglycosides, and sulfonamide. Transconjugants from matings with group I donors were of varied antibiotypes, inheriting resistance to up to 11 of the 13 antibiotics. Resistances to trimethoprim and polymyxin B were never observed to transfer.
E. coli
transconjugants of each group were capable of transferring multiple-antibiotic resistance to several other members of the family
Enterobacteriaceae
. All group II
S. marcescens
and
E. coli
donors and all group I
S. marcescens
donors transferred carbenicillin, streptomycin, kanamycin, gentamicin, tobramycin, and sisomicin resistance to
Pseudomonas aeruginosa
. The results suggest that these
S. marcescens
strains harbor R factors of a broader host range than previously reported.
Pharmacokinetics of Cefamandole in Patients with Renal Impairment
Authors: Czerwinski Anthony W. , Pederson James A.
Published: June 2012

Cefamandole pharmacokinetics were investigated in 24 adult males with stable renal function and creatinine clearances of 0 to 139 ml/min. After intramuscular injection of 1.0 g of cefamandole, peak plasma concentrations were achieved between 1 and 2 h. Maximum plasma concentration and drug half-life increased as creatinine clearance decreased; i.e., with normal renal function the half-life was 1.49 ± 0.10 h, and in anephrics the half-life was 11.48 ± 1.91 h. The greatest increase in half-life occurred when the creatinine clearance was less than 20 ml/min. At these levels of renal impairment, there was significant variance in calculated half-life among patients. The maximum urine concentration and rate of cefamandole urinary excretion decreased as renal function declined. Evidence suggesting renal and nonrenal methods of drug elimination is presented. Hemodialysis resulted in increased cefamandole elimination.
Plasmid-Mediated Ampicillin Resistance in
Haemophilus ducreyi
Authors: Brunton James L. , Maclean Ian , Ronald Allan R. , Albritton William L.
Published: June 2012

Three of 19 strains of
Haemophilus ducreyi
, isolated during a recent outbreak of chancroid, were found to produce β-lactamase and to harbor a 6.0 × 10
6
-dalton plasmid.
Escherichia coli
transformed with this plasmid acquired β-lactamase-mediated resistance to ampicillin. The guanine-plus-cytosine content of the plasmid was found to be 41 mol%. Restriction endonuclease digestion studies suggest that a relatively large portion of the Tn
1
translocon is carried by this plasmid. Whereas this plasmid could not be transferred to
H. influenzae
by mating on membrane filters, a strain of
H. ducreyi
was able to receive and donate a 30 × 10
6
-dalton ampicillin resistance plasmid from
H. influenzae
. The ability of
H. ducreyi
to receive and donate conjugative plasmids may result in the appearance of multiply resistant strains.
Effect of Clavulanic Acid on the Minimum Inhibitory Concentration of Benzylpenicillin, Ampicillin, Carbenicillin, or Cephalothin Against Clinical Isolates Resistant to Beta-Lactam Antibiotics
Authors: Dumon L. , Adriaens P. , Anné J. , Eyssen H.
Published: June 2012

The effect of clavulanic acid on the minimum inhibitory concentration of benzylpenicillin, ampicillin, carbenicillin, or cephalothin against 353 clinical isolates of penicillin- and/or cephalothin-resistant strains was estimated.
Antibiotic Susceptibility of
Streptococcus mutans
: Comparison of Serotype Profiles
Authors: Little Wayne A. , Thomson Lynn A. , Bowen William H.
Published: June 2012

A total of 82 strains of
Streptococcus mutans
representing serotypes
a
through
g
were tested for susceptibility to erythromycin, penicillin, methicillin, lincomycin, tetracycline, vancomycin, gentamicin, streptomycin, neomycin, kanamycin, bacitracin, and polymyxin B. Strains included stock cultures and isolates from human and animal dental plaque. Minimal inhibitory concentrations were determined by a broth-microdilution procedure. The major differences in antibiotic susceptibility observed among the serotypes resulted with antibiotics which act on the cell surface. Bacitracin was most active against serotype
a
strains and polymyxin B against serotype
b
strains. Serotypes
a, d
, and
g
were less susceptible than the other serotypes to methicillin.
Clinical Pharmacology of Intravenously Administered Trimethoprim-Sulfamethoxazole
Authors: Grose William E. , Bodey Gerald P. , Loo Ti Li
Published: June 2012

Pharmacokinetic studies of intravenously administered trimethoprim-sulfamethoxazole (TMP-SMX) were conducted in 11 patients with cancer while they received therapy with this drug combination for infection. Each patient received 160 mg of TMP and 800 mg of SMX every 8 h. The highest plasma concentrations of both agents were attained at the end of a 1-h infusion period, and the levels were maintained above 38 μg of free SMX and 2 μg of TMP per ml for 2 to 4 h on day 1. On day 4, these concentrations were exceeded at all time intervals of blood sampling. High concentrations of TMP and free SMX were recovered in the urine during the 8-h period. The plasma half-lives of TMP and free SMX, as determined during the first 8-h period, were 7.6 and 8.6 h, respectively. Compared with SMX, TMP had an approximately 2.5 times higher volume of distribution. This drug combination was well tolerated by the patients and unaccompanied by drug-related toxicity.
Bacampicillin, Ampicillin, Cephalothin, and Cephapirin Levels in Human Blood and Interstitial Fluid
Authors: Tan James S. , Salstrom Sara-Jane
Published: June 2012

The diffusibility of bacampicillin, ampicillin, cephalothin, and cephapirin into human interstitial fluid was investigated by using crossover studies. We compared bacampicillin with ampicillin and found that bacampicillin was better absorbed after oral administration. Blood, interstitial fluid, and urine levels were consistently higher in volunteers who received bacampicillin. We compared cephalothin with cephapirin and found that blood and interstitial fluid levels were comparable throughout the study.
Thienamycin: New Beta-Lactam Antibiotic with Potent Broad-Spectrum Activity
Authors: Weaver Susanne S. , Bodey Gerald P. , LeBlanc Barbara M.
Published: June 2012

Thienamycin, a new beta-lactam antibiotic, exhibited potent, broad-spectrum activity in vitro against gram-negative bacilli and gram-positive cocci, including many isolates resistant to currently available antibiotics. All isolates were inhibited at concentrations less than or equal to 25 μg/ml, with the exception of 12% of isolates of
Enterobacter
spp. and 3% of isolates of
Serratia marcescens
. Its activity decreased with an increase in inoculum concentration of from 10
5
to 10
7
cells per ml.
Physical Characterization of Ten R Plasmids Obtained from an Outbreak of Nosocomial
Klebsiella pneumoniae
Infections
Authors: Sadowski Peter L. , Peterson Bryan C. , Gerding Dale N. , Cleary Paul P.
Published: June 2012

Gentamicin resistance in
Klebsiella pneumoniae
involved in an outbreak at the Minneapolis Veterans Administration Hospital was due to a transmissible R plasmid. In addition to gentamicin, this plasmid conferred resistance to tobramycin, kanamycin, ampicillin, carbenicillin, cephalothin, chloramphenicol, and sulfathiazole. R plasmids which transferred this complex antibiogram were identified in several clinical isolates, including four different serotypes of
K. pneumoniae, Escherichia coli, Enterobacter cloacae
, and
Proteus morganii
. The covalently closed circular form of all R plasmids isolated had a sedimentation coefficient of 76S to 77S, corresponding to a molecular weight of 58 × 10
6
. The possibility that a single R plasmid was responsible for the dissemination of multiple drug resistance among all of these different clinical strains was examined by characterizing the plasmids by using
Eco
RI restriction endonuclease. The same 15 fragments were obtained from each of the 10 plasmids analyzed. Their molecular weights ranged from 4 × 10
5
to 11 × 10
6
. Thus, we conclude that each of the 10 plasmids present in the various clinical strains isolated from the hospital over a 7-month period originated from a common source and that R plasmid transfer was important in their spread.
In Vitro Antibacterial Activity and β-Lactamase Stability of SCE-129, a New Cephalosporin
Authors: Neu Harold C. , Fu Kwung P.
Published: June 2012

SCE-129 [3-4-carbamoyl-1-pyridiniomethyl-7β- (
d
-α-sulfophenylacetamido)-ceph-3-em-4-carboxylate] is a cephalosporin that inhibits
Pseudomonas aeruginosa
and
Staphylococcus aureus
. SCE-129 is tenfold more active than carbenicillin in inhibiting
P. aeruginosa
. SCE-129 has poor activity against
Enterobacteriaceae
compared with other cephalosporins and is 16-fold less active than the cephalosporins against streptococci. The activity of SCE-129 does not correlate with β-lactamase stability, although SCE-129 is resistant to hydrolysis by gram-positive and gram-negative bacteria. The compound does not inhibit the hydrolysis of other cephalosporins. Although SCE-129 acts synergistically with gentamicin to inhibit some
Pseudomonas
, this cannot be predicted based on knowledge of resistance to one or more compounds.
Pharmacokinetics and Safety of Cefamandole in Newborn Infants
Authors: Agbayani M. M. , Khan A. J. , Kemawikasit P. , Rosenfeld W. , Salazar D. , Kumar K. , Glass L. , Evans H. E.
Published: June 2012

Cefamandole, a new parenteral cephalosporin antibiotic, was administered to 23 newborn infants with pustular skin infection due to
Staphylococcus aureus
for an average duration of 7.5 days. All the patients improved clinically. Elevation of serum glutamic oxaloacetic transaminase and eosinophilia were observed in nine infants each transiently during treatment. There were no abnormalities of renal functions and Coombs' test results remained negative. The levels of cefamandole in serum after either intravenous or intramuscular administration were higher and the mean life was longer than those previously reported in older infants, children, and adults.
Phosphonopeptides as Antibacterial Agents: Mechanism of Action of Alaphosphin
Authors: Atherton Frank R. , Hall Michael J. , Hassall Cedric H. , Lambert Robert W. , Lloyd William J. , Ringrose Peter S.
Published: June 2012

The novel antibacterial peptide mimetic alaphosphin (
l
-alanyl-
l
-1-aminoethylphosphonic acid) selectively inhibited peptidoglycan biosynthesis in both gram-negative and gram-positive bacteria. It induced accumulation of uridine diphosphate-
N
-acetyl-muramyl-tripeptide in gram-positive organisms and significantly reduced the intracellular pool levels of
d
-alanine. Alaphosphin was actively transported into bacterial cells by stereospecific peptide permeases and was subsequently hydrolyzed by intracellular aminopeptidases to yield
l
-1-aminoethylphosphonic acid. This alanine mimetic rapidly accumulated inside susceptible cells to yield a concentration which was 100- to 1,000-fold in excess of that of the precursor peptide in the surrounding medium. In the case of susceptible gram-negative organisms, it was shown that 1-aminoethylphosphonic acid was incorporated into a metabolite which was tentatively identified as uridine diphosphate-
N
-acetylmuramyl-aminoethylphosphonate. The primary intracellular target site of 1-aminoethylphosphonic acid was alanine racemase (EC 5.1.1.1), which was reversibly and competitively inhibited in the gram-negative organisms
Escherichia coli
and
Pseudomonas aeruginosa
and irreversibly inhibited in a time-dependent manner in the gram-positive organisms
Staphylococcus aureus
and
Streptococcus faecalis
. A secondary target site could be uridine diphosphate-
N
-acetylmuramyl-
l
-alanine synthetase [EC 6.3.2.8(b)]. The mechanism of action of alaphosphin may be regarded as involving at least three stages: (i) active transport by peptide permeases; (ii) intracellular peptidase cleavage; and (iii) action of
l
-1-aminoethylphosphonate on alanine racemase.
Effect of Fatty Acyl Group and Sterol Composition on Sensitivity of Lecithin Liposomes to Imidazole Antimycotics
Authors: Yamaguchi Hideyo , Iwata Kazuo
Published: June 2012

The specific affinity for membrane lipids and the membrane selectivity of three imidazole derivatives, clotrimazole, miconazole, and econazole, were studied using various types of liposomes with respect to the lecithin fatty acyl group composition and the liposome content and composition of sterol as membrane models. The sensitivity of liposomes to these drugs was primarily dependent upon the lecithin fatty acyl group composition. With sterol-free liposome systems, each imidazole induced maximum release of trapped glucose as a marker from the unsaturated dioleoyl lecithin liposomes, minimum release from the saturated dipalmitoyl lecithin liposomes, and intermediate release from egg lecithin liposomes. The sensitivity of the dipalmitoyl lecithin liposomes to any imidazole drug was not influenced by the incorporation of cholesterol or ergosterol. On the other hand, clotrimazole-induced permeability changes of liposomes prepared from unsaturated dioleoyl lecithin or egg lecithin were greatly enhanced by the incorporation of ergosterol, whereas they were suppressed by cholesterol incorporation. The sensitivity of liposomes prepared from these unsaturated lecithins to miconazole and econazole was also augmented by ergosterol incorporation, although it was scarcely altered by cholesterol incorporation. Negatively charged liposomes were more sensitive to the three imidazole drugs than positively charged liposomes.
Variability of Agar Dilution-Replicator Method of Yeast Susceptibility Testing
Authors: Brass Corstiaan , Shainhouse J. Zevi , Stevens David A.
Published: June 2012

The agar dilution method of in vitro susceptibility testing of fungi was analyzed with a Steers-type inoculum replicator, ten strains, and three drugs. The replicator reproducibly delivered the same inoculum to each series of plates. The minimal inhibitory concentrations of ketoconazole (an imidazole) and 5-fluorocytosine, but not that of the polyene nystatin, were dependent on the initial inoculum size. With the former two drugs, but not with the latter, minimal inhibitory concentrations were highly variable depending on the time of reading. Results with agar and broth dilution methods were divergent, and the differences in minimal inhibitory concentrations were variable in serial comparisons by the two methods. If the agar dilution minimal inhibitory concentrations were determined at first appearance of control growth, a commonly used end point, small variations in the time of reading (as could occur by variation in observer perception of when initial growth appears) induced large variations in the minimal inhibitory concentrations of 5-fluorocytosine and ketoconazole, particularly with rapidly growing strains. Results at 35 and 30°C were similar. The differences in results with the three drugs suggest different mechanisms of action. The variability quantitated with the agar dilution method could result in variability in results between laboratories and even observers in the same laboratory.
Emergence of Resistance to Cefamandole: Possible Role of Cefoxitin-Inducible Beta-Lactamases
Authors: Sanders Christine C. , Sanders W. Eugene
Published: June 2012

Selection of resistance to cefamandole has been observed, and the drug has failed to protect animals lethally infected with certain
Enterobacteriaceae
that appeared to be highly susceptible in vitro. Using spectrophotometric assays, some of these organisms were found to produce beta-lactamases highly active against cefamandole. Cefoxitin, a poor enzyme substrate, was found to be superior to both cephalothin and cefamandole in induction of these enzymes. A simple disk induction test was developed and used to examine 147
Enterobacteriaceae
for production of these beta-lactamases. The enzymes were found in 69% of cephalothin-resistant, cefamandole-susceptible strains and in only 3% of strains susceptible to both cephalothin and cefamandole. They were most prevalent among isolates of
Enterobacter
, indole-positive
Proteus
, and
Serratia
. Since selection of resistance and therapeutic failures have occurred most often among these genera, the relationship between presence of inducible enzymes and outcome of therapy should be examined further in humans.
Plasmid-Related Transmissibility and Multiple Drug Resistance in
Streptococcus faecalis
subsp.
zymogenes
Strain DS16
Authors: Tomich P. K. , An F. Y. , Damle S. P. , Clewell D. B.
Published: June 2012

Streptococcus faecalis
subsp.
zymogenes
strain DS16 was found to harbor two plasmids, designated pAD1 (35 megadaltons) and pAD2 (15 megadaltons). pAD1 is transmissible and determines a hemolysin-bacteriocin, whereas pAD2 is non-conjugative and determines resistance to erythromycin, streptomycin, and kanamycin. pAD2 could be mobilized by pAD1, but usually involved formation of a pAD1-pAD2 cointegrate.
Inhibition of Transpeptidase Activity in
Escherichia coli
by Thienamycin
Authors: Moore Brian A. , Jevons Sidney , Brammer Keith W.
Published: June 2012

Thienamycin was shown to be a more potent inhibitor than ampicillin of the enzyme peptidoglycan transpeptidase from
Escherichia coli
.
Correlation of Netilmicin Disk Diffusion Susceptibility and Agar Dilution Susceptibility
Authors: Fu Kwung P. , Neu Harold C.
Published: June 2012

The minimal inhibitory concentration of netilmicin determined by the agar dilution method was correlated with the disk diffusion zone of inhibition against 322 clinical isolates. Regression line analysis revealed good correlation,
r
= −0.90, and suggested that isolates with zone sizes ≤14 mm should be considered resistant.
In Vitro Activity of Cefotaxime Against Cephalothin-Resistant Clinical Isolates
Authors: Van Landuyt H. W. , Pyckavet M.
Published: June 2012

Cefotaxime is more active than six other cephalosporins against 150 cephalothin-resistant
Enterobacteriaceae
strains and is the only drug which is more active than ampicillin against
Haemophilus
. It shows a potentially useful activity against
Pseudomonas
.
Comparison of a Micromethod for Performance of the Serum Bactericidal Test with the Standard Tube Dilution Method
Authors: Prober Charles G. , Dougherty Susan S. , Vosti Kenneth L. , Yeager Anne S.
Published: June 2012

A micromethod for performance of the serum bactericidal test is described, and the results obtained with this method are compared with those obtained with the standard tube dilution macromethod. An agreement within ± 1 dilution was achieved in 23 of 25 (92%) determinations of the serum bactericidal titer. The micromethod used approximately one-third of the amount of pooled normal human serum and of the technician's time required for performance of the macromethod. The micromethod offers an accurate and economical alternative to the macromethod for the performance of the serum bactericidal test and is particularly useful with infants and children since it minimizes blood loss.
Human Fibroblast Interferon for Clinical Trials: Production, Partial Purification, and Characterization
Authors: Billiau Alfons , Van Damme Jo , Van Leuven Fred , Edy Victor G. , De Ley Marc , Cassiman Jean-Jacques , Van Den Berghe Herman , De Somer Piet
Published: June 2012

The production and partial purification of human fibroblast interferon for performing clinical trials is described. The interferon was produced by superinduction (exposure to riboinosinic-ribocytidylic acid, cycloheximide, and actinomycin D) of large numbers of human diploid fibroblast cultures. The yield averaged 750 units per cm
2
of culture area. The interferon was concentrated and purified by a two-step procedure involving acid desorption from controlled-pore glass beads and dialysis against polyethylene glycol. Human plasma protein was added as a stabilizer. The lyophilized end product had a specific activity of 0.5 × 10
6
to 1 × 10
6
units/mg of protein; it could be reconstituted for injection at a concentration of 2 × 10
6
units/ml. The composition of this interferon was characterized by crossed immunoelectrophoresis with polyspecific antibodies prepared against the principal sources of potential contaminants: human serum, calf serum, and normal human fibroblasts. Several components of each source were detected. Although the major component of calf serum, bovine serum albumin, was absent, other minor components were retained by the production and purification sequence. One of the main contaminants of fibroblast origin was found to be fibronectin.
Development of Resistance to Amphotericin B in
Candida lusitaniae
Infecting a Human
Authors: Pappagianis D. , Collins M. S. , Hector R. , Remington J.
Published: June 2012

Candida lusitaniae
associated with infection in a patient with acute myelogenous leukemia developed resistance to amphotericin B during systemic treatment of the patient. The organism, when isolated initially, was inhibited by 0.31 μg of amphotericin B per ml in yeast nitrogen base agar, but when isolated (20 days later) just antemortem and postmortem, required 100 and 50 μg/ml, respectively, for complete inhibition at 48 h.
Etiology of Tetracycline-Associated Pseudomembranous Colitis in Hamsters
Authors: Toshniwal Renu , Fekety Robert , Silva Joseph
Published: June 2012

Tetracyclines were implicated in the 1950s in induction of protracted diarrhea and pseudomembranous colitis. Because the pathogenetic mechanism of these illnesses has been questioned recently, we studied tetracycline in hamster models of antibiotic-associated colitis. Orogastric administration of tetracycline caused diarrhea and death, with evidence of hemorrhagic typhlitis. Filtrates of cecal contents were toxic when inoculated into normal hamsters and cell culture monolayers, and toxicity was neutralized with
Clostridium sordellii
antitoxin. Tetracycline-resistant
C. difficile
was cultured from stools of these hamsters, but
Staphylococcus aureus
was not isolated. The value of tetracycline for treatment or prevention of clindamycin-induced colitis in hamsters was also studied, and it was found that daily orogastric administration of tetracycline was poorly protective against clindamycin-induced colitis.
New Rapid Assay for Nafcillin in Serum by Spectrofluorometry
Authors: Lichtenwalner Diane M. , Suh Byungse , Lorber Bennett , Sugar Alan M.
Published: June 2012

A new, rapid method for measuring serum levels of nafcillin by spectrofluorometry is described. The method involves extraction of 2 ml of acidified serum with
n
-butyl chloride, subjecting the organic solvent layer to excitation at 340 nm, and measuring the relative intensity of emission fluorescence at 380 nm. An excellent linear correlation exists between serum levels of nafcillin and the relative intensity in a drug concentration range of 0.25 to 150 μg/ml. The results obtained by this spectrofluorometric technique are in complete accord with those obtained by the conventional microbiological assay using
Staphylococcus aureus
ATCC 6538P. The method is not interfered with by elevated levels of endogenous metabolic products or the presence of other drugs, including a number of antimicrobial agents. The assay is interfered with, however, by the presence of salicylates, for which appropriate correction can easily be made. A salicylate assay employing a spectrofluorometric technique is also described.
Persistence of Plasmid-Carrying Tetracycline-Resistant
Escherichia coli
in a Married Couple, One of Whom Was Receiving Antibiotics
Authors: Petrocheilou V. , Richmond M. H. , Bennett P. M.
Published: June 2012

This paper describes an extension to an earlier account of the coliform flora carried by a married couple, one of whom was taking tetracycline for prolonged periods. The latter phase of this study was notable for the following: first, certain tetracycline-resistant
Escherichia coli
O antigen types persisted in one of the participants for several weeks after tetracycline was withdrawn; second, a course of ampicillin led to replacement of the tetracycline-resistant flora by one that was ampicillin resistant, but the end of the ampicillin course led to the reappearance of the tetracycline-resistant line, even though no tetracycline was being taken; and third, the tetracycline-sensitive O75
E. coli
, which appeared toward the end of the survey, had not lost their plasmid but carried a derivative in which the tetracycline resistance gene(s) had been inactivated by the insertion of an extra piece of deoxyribonucleic acid with a molecular weight of about 1 megadalton.
Competition of beta-lactam antibiotics for the penicillin-binding proteins of Pseudomonas aeruginosa, Enterobacter cloacae, Klebsiella aerogenes, Proteus rettgeri, and Escherichia coli: comparison with antibacterial activity and effects upon bacterial morphology
Authors: Curtis N A , Orr D , Ross G W , Boulton M G
Published: June 2012

The competition of a number of beta-lactam morphogenic probes for the penicillin-binding proteins (PBPs) of Pseudomonas aeruginosa, Enterobacter cloacae, Klebsiella aerogenes, Proteus rettgeri, and Escherichia coli has been studied. The results indicate that the various gram-negative bacteria have similar, but not identical, PBP patterns and that the individual proteins probably perform similar morphogenic functions as in E. coli K-12. Comparison of the 50% binding concentrations of the compounds for the various PBPs of the five strains with their antibacterial activity indicates that the different antibiotics are excluded to a greater or lesser degree by the outer membrane permeability barrier and that the exclusion is most pronounced in P. aeruginosa.
Ceforanide: In Vitro and Clinical Evaluation
Authors: Burch Keith H. , Pohlod Donald , Saravolatz Louis D. , Madhavan Tom , Kiani Daria , Quinn Edward L. , Del Busto Ramon , Cardenas Julio , Fisher Evelyn J.
Published: June 2012

Ceforanide, a new cephalosporin antibiotic with a long half-life (3 h), can be administered twice daily. We evaluated its antimicrobial activity, pharmacology, and clinical efficacy. Twenty-seven patients with infections due to susceptible organisms received ceforanide, 0.5, 1, or 2 g, intramuscularly or intravenously every 12 h for 6 to 28 days. In vitro studies with the clinical isolates from 27 patients treated plus 263 additional isolates showed that ceforanide was active against cephalothin-susceptible gram-positive and gram-negative microorganisms. In addition, ceforanide inhibited 65% of cephalothin-resistant
Escherichia coli
and 65% of
Enterobacter
spp. at ≤12.5 μg/ml. After a single 1-g intramuscular dose, the mean peak plasma concentration at 1 h was 48.9 μg/ml and that at 12 h was 4.7 μg/ml. Plasma accumulation occurred in some patients. The infections included 10 pneumonias, 3 with bacteremia and 1 with empyema; 11 soft tissue infections, 4 with abscesses and 3 with sepsis; and 3 urinary tract infections. One case each of endocarditis, osteomyelitis, and septic thrombophlebitis, all due to
Staphylococcus aureus
, were treated. Clinical response was satisfactory in all patients; bacteriological response was satisfactory in 26 of 27 patients. Ceforanide was well tolerated. Three patients developed mild increases in liver enzymes, and one developed slight eosinophilia. In another case, the antibiotic was discontinued because of a fivefold rise in serum glutamic-oxalacetic transaminase (aspartate aminotransferase) and serum glutamic-pyruvic transaminase (alanine aminotransferase) and a twofold rise in lactic acid dehydrogenase and alkaline phosphatase.
Assay of serum tobramycin levels with the Bactec 460
Authors: Phillips L E , Martin R R , Gentry L O , Rogers T E
Published: June 2012

Serum tobramycin levels of synthetic and patient specimens were determined by the Bactec 460. The results were compared with those obtained from the same specimens by radioimmunoassay. These studies suggest that assays performed by either method should be run in duplicate or triplicate to achieve maximum accuracy. The studies also suggest that results obtained by the Bactec method are at least as reliable as those obtained by the radioimmunoassay method.
Antimicrobial susceptibility of clinical isolates of Serratia marcescens
Authors: Alvarez J S , Regueiro B , Garrido M J
Published: June 2012

The in vitro susceptibilities of 242 isolates of Serratia marcescens to 17 antibacterial drugs have been determined. Oxolinic acid, nalidixic acid, cefoxitin, and amikacin were the most active drugs. Ampicillin, kanamycin, and cephalothin were among the least active. A 4-year study showed that resistance of S. marcescens to dibekacin, tobramycin, sisomycin, and gentamicin has increased at least one order of magnitude in that period, whereas resistance to amikacin showed but a twofold increase.
Erythromycin and clindamycin resistance in Corynebacterium diphtheriae from skin lesions
Authors: Coyle M B , Minshew B H , Bland J A , Hsu P C
Published: June 2012

Erythromycin- and clindamycin-resistant Corynebacterium diphtheriae isolates were recovered from skin lesions. Resistance to erythromycin and clindamycin was induced by a subinhibitory concentration (0.03 microgram/ml) of erythromycin. Clindamycin (0.07 microgram/ml) was a more effective inducer of its own resistance than of erythromycin resistance. Erythromycin-inducible cross-resistance to vernamycin B alpha was demonstrated in disk diffusion tests.
Antibacterial activity of ceftizoxime (FK 749), a new cephalosporin, against cephalosporin-resistant bacteria, and its stability to beta-lactamase
Authors: Kojo H , Nishida M , Goto S , Kuwahara S
Published: June 2012

Antibacterial activity of FK 749 against ampicillin-resistant clinical isolates of Escherichia coli was compared with those of other newly developed cephalosporins. FK 749 was the most active against strains possessing R-plasmids specifying ampicillin resistance and those whose resistance was chromosomally determined. The susceptibility of ampicillin-susceptible E. coli to FK 749 was not decreased by transduction of ampicillin resistance-specifying plasmids. However, most of the transconjugants acquired a high level of resistance to cefoperazone and cefamandole and a moderate level of resistance to cefoperazone and cefamandole and a moderate level to cefotiam. FK 749 was highly stable to both penicillinase- and cephalosporinase-type beta-lactamases, including R-plasmid-mediated beta-lactamase. Its level of resistance to beta-lactamases was comparable to those of cefoxitin, cefmetazole, and cefotaxime, slightly superior to that of cefuroxime, and much superior to those of cefotiam, cefamandole, and cefoperazone.
Amantadine aerosol in humans
Authors: Knight V , Bloom K , Wilson S Z , Wilson R K
Published: June 2012

Seven well volunteers and three patients with a naturally occurring influenza A/USSR/77 (H1N1)-like infection were given amantadine by small-particle aerosol with a Collison generator modified for this purpose. Inhalation periods for the volunteers were increased on consecutive weekends from 15 min to 1 h, 4 h, 9 h, and 2 consecutive days of 6 h each. The particle size was 1.2-micrometer mass median diameter, and the concentration of inhaled aerosol ranged from 47 to 75 microgram/liter. Estimates of retained doses in 9 h were 74 to 149 mg. About two-thirds of the dose was recovered in the urine. Pulmonary function studies did not vary significantly from base-line values and were within a normal range for five of seven volunteers. Two volunteers with a moderate reduction in mid-maximal flow before exposure had a total of three episodes of coughing and wheezing associated with moderate reductions in mid-maximal flow values. These episodes cleared spontaneously or improved promptly after isoproterenol therapy. The patients with influenza tolerated the treatment well and recovered promptly.
Clinical Pharmacokinetics and Safety of High Doses of Ceforanide (BL-S786R) and Cefazolin
Authors: Smyth Robert D. , Pfeffer Morris , Donald Aaron Glick , Van Harken R. , Hottendorf Girard H.
Published: June 2012

The pharmacokinetics and safety of ceforanide and cefazolin were compared in normal subjects after 30-min intravenous infusions of 2-, 3-, and 4-g single doses and 4-g twice-daily doses for 10 days. No significant differences were observed in plasma-renal pharmacokinetic parameters between single and multiple doses of ceforanide. Half-life (
t
½
, 2.8 h), plasma clearance (

Cl
p

, 48 ml/min per 1.73 m
2
), and renal clearance (
Cl
0−12h

r

, 47 ml/min per 1.73 m
2
; tubular secretion, 44%, and glomerular filtration, 56%) did not change with increased dose or on multiple dosing. No significant change was observed in
t
½
(1.9 h), area under the plasma concentration-time curve,

Cl
r

(60 ml/min per 1.73 m
2
; tubular secretion, 80%, and glomerular filtration, 20%), or

Cl
p

(75 ml/min per 1.73 m
2
) for 4-g single doses compared with twice-daily administration of cefazolin. A small increase in cefazolin clearance was observed when plasma concentrations were greater than 100 μg/ml, when the single dose was increased from 2 to 4 g; this was a result of the decrease in percentage of plasma protein binding and increased renal clearance due to increased glomerular filtration. The increase in renal clearance resulted in a lack of linear proportionality of the plasma area under the curve with dose over a range of 2 to 4 for both cephalosporins, although this effect was much less marked with ceforanide. Both compounds were well tolerated both locally and systemically. There was no evidence of any change in renal function based on clearances of drug,
p
-aminohippuric acid, or creatinine, and other standard clinical parameters.
Minimal inhibitory concentrations of 34 antimicrobial agents for control strains Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853
Authors: Fass R J , Barnishan J
Published: June 2012

The use of control strains of bacteria is important to monitor the accuracy and precision of antimicrobial susceptibility testing. Knowledge of the minimal inhibitory concentrations of commonly used organisms would be useful to achieve a degree of inter- as well as intra-laboratory reproducibility. The minimal inhibitory concentrations of 34 antimicrobial agents for control strains Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853, as determined by a microdilution method in cation-supplemented Mueller-Hinton broth, are reported.
Evaluation of the Bactec serum gentamicin assay
Authors: Manos J P , Jacobs P F
Published: June 2012

A radiometric assay for gentamicin was compared with an established radioimmunoassay protocol. The coefficients of variation for within-run, day-to-day, and overall runs were consistently higher for the radiometric method as compared with the radioimmunoassay. The coefficient of correlation for 84 patient sera tested by the two methods for gentamicin levels was 0.82. Though less precise, the radiometric method was felt to be an acceptable means of determining gentamicin levels in laboratories where the radioimmunoassay is unavailable.
Induction and prevention of experimental arteriovenous fistula infections
Authors: Lane T W , Abrutyn E
Published: June 2012

Arteriovenous fistulae (AVF) between the femoral vessels were prepared in 20 rabbits to determine if local endovascular infections could be induced and if antibiotic prophylaxis could prevent infection. Twenty-four hours after bacterial challenge with 10(6) Staphylococcus aureus all 20 AVF were culture positive, whereas 19 of the 20 contralateral, unoperated femoral vessels were sterile. Two rabbits with AVF, followed for 30 days after receiving staphylocci, had intermittently positive blood cultures and had positive cultures of the AVF and heart valves at autopsy. Two groups of ten rabbits with AVF received either prophylactic oxacillin or vancomycin 0.5 h before bacterial challenge. Only 2 of 10 animals receiving oxacillin and 1 of 10 receiving vancomycin had positive AVF cultures at 24 h, a significant reduction in the incidence of endovascular infection compared with that in controls (P less than 0.001 by Fisher's exact test). This model, which reliably results in infection, can be used to study the pathophysiology, prevention, and treatment of AVF infections.
Relative potencies of different anti-herpes agents in the topical treatment of cutaneous herpes simplex virus infection of athymic nude mice
Authors: Descamps J , De Clercq E , Barr P J , Jones A S , Walker R T , Torrence P F , Shugar D
Published: June 2012

Thirteen established anti-herpes compounds have been directly compared in a single assay system for their effects on the development of herpetic skin lesions, and mortality associated therewith, in athymic nude (nu/nu) mice inoculated intracutaneously with herpes simplex virus type 1 (KOS). When applied topically (at 1% in a water-soluble ointment), phosphonoacetic acid, E-5-(2-bromovinyl)-2'-deoxyuridine, acycloguanosine, and trisodium phosphonoformate emerged as the most active agents.
Cerebrospinal Fluid Diffusion of Kanamycin in Newborn Infants
Authors: McDonald Louise L. , Geme Joseph W. St.
Published: June 2012

Cerebrospinal fluid (CSF) diffusion of kanamycin was studied in 35 newborn infants. Five infants had bacterial meningitis and two had viral meningitis. One-half of the infants received an intramuscular injection of 7.5 mg of kanamycin per kg, whereas the other half received 12.5 mg/kg. Serum and CSF specimens were obtained 3 to 6 hr and 11 to 12 hr after injection. No significant difference was observed between serum levels of kanamycin after the 7.5 and 12.5 mg/kg doses at either sampling time. However, at 3 to 6 hr, in those infants without meningitis, there was a significantly higher concentration of kanamycin in the CSF after the larger 12.5 mg/kg dose. CSF levels of kanamycin did not rise to the desirable therapeutic range with either dose. We were unable to draw a definite conclusion regarding the CSF diffusion of kanamycin in bacterial meningitis, but our data suggest that complete confidence in intramuscular kanamycin in the treatment of gram-negative neonatal meningitis may not be justified, even in those cases with a brisk inflammatory response.
Rifamycins: Modulation of Specific Anti-Poxviral Activity by Small Substitutions on the Piperazinyliminomethyl Side Chain
Authors: Moss Bernard , Rosenblum Edith N. , Grimley Philip M. , Mims Sharon J.
Published: June 2012

Rifamycin derivatives differing in the substitutent at the 4 position of the piperazinyliminomethyl side chain were tested for anti-poxviral activity. The effects of each derivative on wild-type vaccinia virus and on a mutant selected for resistance to rifampin were determined. Antiviral activity was measured in tissue culture by plaque inhibition, reduction in virus yield, and specific interruption of virus morphogenesis. Rifamycin derivatives containing H, ethyl, or propyl groups at the 4 position of the piperazinyliminomethyl side chain were much less active than rifampin, which has a methyl group at this position. Thus, minimal shortening or lengthening of the methyl piperazinyliminomethyl side chain of rifampin led to loss of specific antiviral activity. In contrast, the derivative containing an amino group at the 4 position of the piperazinyliminomethyl side chain had enhanced anti-poxviral activity.
Susceptibility of Mycobacteria to Rifampin
Authors: Woodley Charles L. , Kilburn James O. , David Hugo L. , Silcox Vella A.
Published: June 2012

The
Mycobacterium
species
M. tuberculosis, M. avium-intracellulare, M. kansasii, M. marinum, M. scrofulaceum, M. fortuitum, M. terrae
, and
M. gordonae
were analyzed for their susceptibility to rifampin.
M. tuberculosis, M. kansasii
, and
M. marinum
were susceptible to the antibiotic, and resistant populations developed as a result of the interplay of mutation and selection. The mutation rates (susceptibility → resistance) were calculated to be 4.9 × 10
−10
and 1.7 × 10
−9
mutations per bacterium per generation in, respectively,
M. kansasii
and
M. marinum. M. fortuitum
was found to be naturally resistant to the antibiotic, whereas the nature of resistance in the other species was unclear and is discussed.
Interaction of a New Cephalosporin, 7-Cyanacetamidocephalosporanic Acid, with Some Gram-Negative and Gram-Positive β-Lactamase-Producing Bacteria
Authors: Russell A. D.
Published: June 2012

When gram-negative β-lactamase-producing bacteria were incubated at 37 C in broth containing 100 to 250 μg or more of 7-cyanacetamidocephalosporanic acid (CAA) per ml, a red or orange color developed, irrespective of whether or not growth had occurred. This color development was paralleled by breakdown of CAA by
Escherichia coli
R
+
TEM, although there was a concurrent lethal effect on the cells. No red color developed with gram-positive or gram-negative strains that did not produce β-lactamase. Several methicillin-susceptible β-lactamase-producing strains of
Staphylococcus aureus
produced a faint red color, as did one of four penicillin acylase-producing
E. coli
strains. No color resulted when two methicillin-resistant, β-lactamase-nonproducing
S. aureus
strains were tested. Two methicillin-resistant, β-lactamase-producing
S. aureus
strains produced a bright red color at 37 C, but a much fainter one at 30 C.
Binding of Dihydrostreptomycin to
Escherichia coli
Ribosomes: Kinetics of the Reaction
Authors: Chang F. N. , Flaks Joel G.
Published: June 2012

Investigations were carried out on the binding of dihydrostreptomycin to purified (and reassociated) 70
S
ribosomes and 30
S
subunits from streptomycin-susceptible strains, and the results were compared with those of similar studies with native (run-off) 70
S
ribosomes. At 0 C, only a small fraction of purified 70
S
ribosomes and 30
S
sub-units bound 1 molecule of the antibiotic tightly, and at a rate comparable to the binding occurring with native 70
S
ribosomes. At temperatures of 10 C and above, there was a temperature-dependent increase in the extent of antibiotic binding to purified 70
S
and 30
S
particles up to a maximum of 1 molecule/ribosomal particle, but the kinetics of binding was slow in comparison to that taking place at 0 C. These and other results suggest that a major fraction of 30
S
subunits and purified (or reassociated) 70
S
ribosomes are inactive in binding the antibiotic. This has been localized to an instability of the free 30
S
subunit, which in solution at 0 C has a half-life of 5 hr or less. Inactive 30
S
or 70
S
particles could be thermally activated, with the latter being identical in their streptomycin-binding properties to native 70
S
ribosomes. The activation kinetics were slow in comparison to the binding kinetics for the antibiotic and were indicative of a conformational change in ribosomal structure. There thus appears to be a reversible transition between active and inactive forms of the ribosomal particles for streptomycin binding, but additional binding sites for the antibiotic are not created by the transitions. The active form of the 30
S
subunit can be stabilized in the presence of polyuridylic acid, but much more effectively by association with the 50
S
subunit to form a 70
S
ribosome. The kinetics of dihydrostreptomycin binding were studied in both directions of the reaction, and the reaction in the direction of binding was found to be several orders of magnitude faster than that of the reverse, or debinding, direction. The kinetics of the exchange of bound dihydrostreptomycin with the free antibiotic were also determined and shown to have rate constants that are very similar to those of the debinding reaction, which is the rate-limiting step. It appears likely that the exchange reaction is proceeding via the same reaction pathway. The temperature dependence of the kinetics of dissociation of the bound complex was much greater than that in the direction of binding and accounted for most of the temperature dependence of the binding equilibrium. From the determined thermodynamic and activation parameters, it appears likely that binding of the antibiotic induces a conformational change in ribosomal structure to one that is less ordered than the native particle. Heterogeneity has been found in the kinetics of binding and of exchange, with a fraction of the 70
S
population showing slower kinetics for both directions of the reaction.
Standardized Antimicrobial Disc Susceptibility Testing of Anaerobic Bacteria: In Vitro Susceptibility of
Clostridium perfringens
to Nine Antibiotics
Authors: Sapico Francisco L. , Kwok Yung-Yuan , Sutter Vera L. , Finegold Sydney M.
Published: June 2012

The in vitro susceptibility of 43 strains of
Clostridium perfringens
to nine antibiotics was determined by a standardized test for rapid-growing anaerobes. Good correlation was established between the agar dilution susceptibility and the disc diffusion susceptibility results. The inhibition zone diameters around the antibiotic discs, however, were generally much smaller than those of gram-negative anaerobes previously studied. All of the strains tested were susceptible in vitro to chloramphenicol, clindamycin, doxycycline, minocycline, penicillin, and vancomycin. Erythromycin showed poor in vitro activity against this organism, with only 7% of the strains susceptible, 72% intermediate in susceptibility, and 21% resistant. In tests of the 43 strains against lincomycin, 58% were susceptible, 32.5% were intermediate in susceptibility, and 9.5% were resistant. Against tetracycline, 37% of the strains were intermediate in susceptibility and the rest were susceptible.
Failure of Rifampin to Inhibit Adenovirus Replication
Authors: McCormick David P. , Wenzel Richard P. , Smith Edward P. , Beam Walter E.
Published: June 2012

Rifampin failed to inhibit adenovirus replication in tissue culture. The data suggest that rifampin would be ineffective as a chemotherapeutic agent against adenovirus disease.
Suppression of Intrinsic Resistance to Methicillin and Other Penicillins in
Staphylococcus aureus
Authors: Sabath L. D. , Wallace Steven J. , Gerstein Deborah A.
Published: June 2012

The
p
H of the medium in which staphylococcal susceptibility to penicillins was determined was found to make a profound difference (128- to 8,000-fold) in the expression of “intrinsic” resistance, whereas β-lactamase-mediated resistance was only slightly affected by
p
H; methicillin-resistant staphylococci that are β-lactamase-negative are models of pure intrinsic resistance, and the common β-lactamase-producing organisms (methicillin-susceptible) are examples of pure β-lactamase-mediated resistance. Methicillin-resistant staphylococci were unable to express their resistance at
p
H 5.2. However, growth of methicillin-resistant organisms in acid (
p
H 5.2) medium, followed by susceptibility testing at
p
H 7.4, showed no elimination of the genotype for intrinsic resistance, indicating that the
p
H effect was due to suppression, rather than to elimination of the gene determining the intrinsic resistance. These
p
H changes had little effect on the susceptibility of staphylococci that possessed neither intrinsic resistance nor β-lactamase-mediated resistance. Thus, the suppression of “intrinsic” resistance was highly specific, and probably not the result of a change in ionization of the antibiotic, which would have been expected to affect all cells essentially equally. It is unlikely that foci of inflammation in man become sufficiently acid to suppress methicillin resistance of the staphylococci causing infection and inflammation.