bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative In Vitro Appraisal of Piperacillin, Including Its Activity Against
Salmonella typhi
Authors: Robinson Roy G. , Saunders Jean , Cassel Robert , Block Colin S. , Koornhof Hendrik J.
Published: June 2012

Piperacillin was evaluated in vitro against 711 clinical isolates of aerobic and anerobic gram-positive and gram-negative bacteria, including 76 isolates of
Salmonella typhi
. Piperacillin minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were compared with those of a range of β-lactam, aminoglycoside, and other antimicrobial agents, and inoculum size effects were considered. The relationship between dilution and disk diffusion tests was studied by regression analysis. In addition, piperacillin was assessed in combination with aminoglycoside and other β-lactam drugs. This investigation has confirmed the activity of piperacillin against a broad range of bacteria, including
Pseudomonas, Enterobacteriaceae, Neisseria
, β-lactamase-negative
Haemophilus influenzae
, and
Staphylococcus aureus
as well as enterococci,
Bacteroides fragilis
, and other anaerobes. All strains of
Pseudomonas aeruginosa
were inhibited by ≤32 μg/ml or less, demonstrating again the potential usefulness of piperacillin in the treatment of pseudomonal infections.
S. typhi
proved susceptible to piperacillin, all isolates being inhibited by 1 μg/ml. Inoculum size experiments showed that inocula of 10
8
CFU resulted in MICs and MBCs appreciably higher than those resulting from inocula of 10
6
CFU, and inocula of 10
2
CFU resulted in MICs and MBCs appreciably lower than those resulting from inocula of 10
4
CFU. Piperacillin was active against all gentamicin-resistant pseudomonads tested, but not against gentamicin-resistant klebsiellas and enterobacters. Combinations of piperacillin with tobramycin and amikacin were consistently synergistic against
Pseudomonas
and
Serratia
isolates. Less consistent results were shown when piperacillin was combined with aminoglycosides or cephalothin against
Klebsiella
and indole-positive
Proteus
isolates, although synergy was observed in most cases. Occasional antagonistic reactions were encountered with piperacillin-cephalothin or piperacillin-tobramycin combinations against the latter isolates.
In vitro susceptibility of Mycobacterium marinum to eight antimicrobial agents
Authors: Sanders W J , Wolinsky E
Published: June 2012

The in vitro susceptibilities of 16 Mycobacterium marinum strains to eight antimicrobial agents were determined by the agar dilution technique. The most active drugs were amikacin and kanamycin. Tetracycline, doxycycline, and minocycline were inhibitory, predominantly at concentrations slightly below the expected blood and tissue levels. Trimethoprim-sulfamethoxazole and erythromycin demonstrated activity only at concentrations greater than those usually attained in serum and tissues. Gentamicin was relatively inactive.
Therapeutic effects of cefotiam and cefazolin on experimental pneumonia caused by Klebsiella pneumoniae DT-S in mice
Authors: Nishi T , Tsuchiya K
Published: June 2012

The efficacies of several dosage schedules, productive of plasma levels of cefotiam and cefazolin of short and long duration and starting at three levels of cefotiam and cefazolin of short and long duration and starting at three different times (3, 18, and 30h) after infection, were examined in experimental pneumonia caused by Klebsiella pneumoniae DT-S in mice. With each of the multiday regimens there was a large segment of the day when plasma levels fell below assayable concentrations. In all cases, cefotiam proved about eight times as active as cefazolin, indicating that the potent in vitro antibacterial activity of cefotiam was well reflected in the therapeutic effect in this model infection. As judged by the total dose administered, the regimen of cefotiam producing a low but sustained plasma level gave better therapeutic effects than that exhibiting a high but transient plasma level. The cefotiam levels in the plasma of mice that received the regimen effective when initiated at 18 h after infection were less than the expected levels in humans after intravenous infusion of the usual clinical dose.
Antimicrobial susceptibility testing of Streptococcus pneumoniae by micro-broth dilution
Authors: Tarpay M M , Welch D F , Marks M I
Published: June 2012

Thirty-three clinical isolates of Streptococcus pneumoniae were tested for susceptibility to penicillin and ampicillin by a standard agar dilution method. Results were compared to those obtained using a micro-broth dilution technique in which Mueller-Hinton broth was supplemented with 5% difibrinated whole sheep blood. Among the 33 strains, 2 were resistant (minimal inhibitory concentration, 8 micrograms/ml), 10 were relatively resistant (minimal inhibitory concentration, 0.12 to 0.5 micrograms/ml), and 20 were susceptible (minimal inhibitory concentration, less than or equal to 0.06 micrograms/ml) to penicillin by both methods. Only one stain showed a two-dilutional-step difference by micro-broth and agar dilution testing resulting in categorization as relatively resistant by the former method but susceptible by the latter. A 1-microgram oxacillin disk correctly identified 11 of the 12 resistant strains. The micro-broth dilution technique is a reliable, simple method for penicillin or ampicillin susceptibility testing of pneumococci and economically feasibile to perform manually or with a semiautomated system.
Animal model distinguishing in vitro from in vivo carbenicillin-aminoglycoside interactions
Authors: Pieper J A , Vidal R A , Schentag J J
Published: June 2012

Aminoglycosides and carbenicillin are frequently co-administered to patients with serious gram-negative infections. Aminoglycosides are inactivated by carbenicillin in vitro, and a loss of antibacterial activity of both antibiotics results. Although these interactions are presumed to occur in vivo, previous studies have not used assay methodology that can distinguish inactivation occurring prior to and during microbiological assay from inactivation in vivo. To address this problem, we gave seven bilaterally nephrectomized mongrel dogs doses designed to achieve simultaneous therapeutic serum concentrations of aminoglycosides and carbenicillin. Serum samples were tested by radioimmunoassay on three occasions: immediately, to determine in vivo interactions, and at 24 h and 1 week to assess the time course of in vitro inactivation. In comparison with immediate radioimmunoassay, gentamicin and tobramycin concentrations decreased by 39 and 53%, respectively, when assayed at 24 h (P < 0.05) and by 75 and 82% when assayed at 7 days (P < 0.001). In contrast, amikacin concentrations were reduced by only 9 and 30% at 24 h and 7 days. Tobramycin concentrations were also determined by immediate microbiological assay and were found to be similar to those in samples stored for 24 h before radioimmunoassay. Immediate radioimmunoassay demonstrated that carbenicillin reduced in vivo serum half-lives of gentamicin and tobramycin by 40% (P < 0.05). The half-life of amikacin in vivo was not significantly altered. In the presence of carbenicillin, amikacin was the most stable aminoglycoside both in vivo and in vitro, and it is the aminoglycoside of choice in patients with renal failure who require this combination.
Comparative studies of interferon and three antiviral agents on neurotropic and oncogenic herpesviruses
Authors: Daniel M D , Falk L A , King N W , Tamulevich R , Holland J S , Bekesi J G
Published: June 2012

The antiviral effects of four compounds, phosphonoacetate, phosphonoformate, acycloguanosine, and purified human lymphoblastic interferon, were tested against two neurotropic herpesviruses, herpesvirus platyrrhine and herpes simplex virus, and two oncogenic herpesviruses, herpesvirus saimiri and herpesvirus ateles. All four compounds induced different degrees of inhibition of these herpesviruses. Phosphonoacetate and phosphonoformate at concentrations of 50 micrograms/ml or greater showed powerful antiviral activities. Interferon was more effective against herpesvirus saimiri and herpesvirus ateles, the two oncogenic viruses. Herpes simplex virus and the oncogenic herpesviruses were effectively inhibited by acycloguanosine, whereas herpesvirus platyrrhine proved to be resistant. The simian herpesviruses required a higher concentration of phosphonoformate, phosphonoacetate, and acycloguanosine for antiviral action. The antiviral action of all four compounds was contingent on the continued presence of the compounds in the infected cell culture medium.
In vivo interaction of beta-lactam antibiotics with the penicillin-binding proteins of Streptococcus pneumoniae
Authors: Williamson R , Hakenbeck R , Tomasz A
Published: June 2012

The interactions of several beta-lactam antibiotics with the penicillin-binding proteins (PBPs) of Streptococcus pneumoniae have been studied using whole organisms treated with such antibiotics and subsequently with [3H]benzylpenicillin. Differences in chemical structure were shown to cause major and selective changes in the affinities of the beta-lactams for the PBPs Only 4 of the 28 compounds tested induced a specific morphological effect (enlargement of the equatorial region) under the particular conditions tested. In 12 of the 18 beta-lactams studied, a close correlation was found between the minimal inhibitory concentrations and the concentrations required to half-saturate PBP2b. However, such a correlation was no longer apparent when the bacteria were treated with the antibiotics at their minimal inhibitory concentrations. These findings are discussed in the context of various approaches that have been used to identify the growth-inhibitory targets of beta-lactam antibiotics in bacteria.
Bactericidal activity of cerumen
Authors: Chai T J , Chai T C
Published: June 2012

Freshly collected cerumen (dry form) suspended at a concentration of 3% in glycerol-sodium bicarbonate buffer showed bactericidal activity against some strains of bacteria tested. This suspension reduced the viability of Haemophilus influenzae, Escherichia coli K-12, and Serratia marcescens by more than 99%, whereas the viability of two Pseudomonas aeruginosa isolates, E. coli K-1, Streptococcus, and two Staphylococcus aureus isolates of human origin was reduced by 30 to 80%. The results support the hypothesis that cerumen functions to kill certain foreign organisms which enter the ear canal.
Pharmacokinetic comparison of cefroxadin (CGP 9000) and cephalexin by simultaneous administration to humans
Authors: Lecaillon J B , Hirtz J L , Schoeller J P , Humbert G , Vischer W
Published: June 2012

The pharmacokinetic parameters of cefroxadin and cephalexin were compared after simultaneous oral administration of the two cephalosporins to 21 subjects. The influence of the dose, the formulation, and food intake on these parameters was investigated. Both drugs were equally well absorbed from all of the tested formulations; identical percentages of the dose were recovered in the urine in all cases. The elimination half-life of cefroxadin and, consequently, the area under the plasma concentration-time curve were about 10% less than those of cephalexin. Plasma concentrations and cumulative excretion curves of the two drugs were almost superimposable. Food intake had the same effect on both drugs; absorption was slowed, but the amounts absorbed were almost the same as those in fasted subjects.
Effect of prednisolone and rifampin on isoniazid metabolism in slow and rapid inactivators of isoniazid
Authors: Sarma G R , Kailasam S , Nair N G , Narayana A S , Tripathy S P
Published: June 2012

The effect of prednisolone and rifampin, alone and in combination, on the biodisposition of isoniazid in slow and rapid inactivators of isoniazid was investigated. In one investigation, we made serial determinations of plasma isoniazid concentrations up to 8 h and of isoniazid and acetylisoniazid in excreted urine up to 8.5 h in patients receiving isoniazid alone on one occasion and isoniazid plus prednisolone or isoniazid plus rifampin on another. Prednisolone caused a significant decrease in the plasma isoniazid concentrations in both slow and rapid inactivators. It also enhanced the renal clearance of isoniazid in both slow and rapid inactivators and increased the rate of acetylation of isoniazid in slow inactivators only. Rifampin had no effect on the biodisposition of isoniazid in either slow or rapid inactivators. In a second investigation, one group of slow and rapid inactivators received isoniazid and rifampin, and a different group received prednisolone, in addition. Plasma isoniazid concentrations in slow inactivators receiving prednisolone were significantly lower than in those who received isoniazid and rifampin only. In rapid inactivators, plasma isoniazid concentrations were similar in the two groups of patients, suggesting that concomitant administration of rifampin had considerably modified the prednisolone effect on the biodisposition of isoniazid in these patients.
Purification and biochemical properties of beta-lactamase produced by Proteus rettgeri
Authors: Matsuura M , Nakazawa H , Inoue M , Mitsuhashi S
Published: June 2012

beta-Lactamase produced by Proteus rettgeri was found to be a typical cephalosporin beta-lactamase on the basis of its substrate hydrolysis profile. The enzyme activity was enhanced by prior treatment with an inducer. The enzyme was purified 166-fold by carboxymethyl-Sephadex column chromatography which indicated that its molecular weight was 42,000 +/- 2,000 and its isoelectric point was 8.7. Cefoperazone, cefoxitin, cefusulodin, cefmetazole, cefotaxime, 6059-S, FK749, YM-09330, carbenicillin, and cloxacillin were stable to this enzyme and possessed the function of competitive inhibition, as shown by their affinity for the beta-lactamase. The enzyme activity was inhibited by iodine, p-chloromerburibenzoate, and HG2+ ion. Clavulanic acid and CP-45899 displayed poor inhibitory activity toward this enzyme. The optimal pH was 8.0, and the optimal temperature was 50 degrees C.
Method of reliable determination of minimal lethal antibiotic concentrations
Authors: Pearson R D , Steigbigel R T , Davis H T , Chapman S W
Published: June 2012

The lack of a standardized, statistically reliable method for in vitro determinations of the minimal lethal or bactericidal concentrations of antibiotics has complicated analyses of isolates of Staphylococcus aureus which appear to be inhibited but not killed by the usual concentrations of cell wall-active antibiotics. We describe a method which identifies some of the covariants involved in determinations of minimal lethal concentrations. Lethality was defined as a 99.9% reduction in the initial inoculum of bacteria after 24 h of incubation. We limited the sample volume to 0.01 ml to minimize the inhibitory effect of antibiotic and corresponding rejection values, which detected lethality with a high degree of sensitivity and specificity. When the number of colonies on subculture was equal to or less than the rejection value, the antibiotic was considered lethal for the test organism. Rejection values encompassed initial inocula from 10(5) to 10(7) colony-forming units per ml for single and duplicate samples and allowed for 1 or 5% variability in pipette volumes and errors in initial inoculum determinations. This method was used to determine the minimal lethal concentrations of semi-synthetic penicillins for S. aureau isolates, one of which was tolerant to the killing action of penicillin.
Bioavailability and Metabolism of Potassium Phosphanilate in Laboratory Animals and Humans
Authors: Lee Francis H. , Van Harken Donald R. , Vasiljev Michael , Smyth Robert D. , Hottendorf G. H.
Published: June 2012

Phosphanilic acid is an antibacterial agent with a mode of action and antibacterial spectrum similar to those of sulfamethoxazole, with the exception that it has potent antipseudomonal activity. Bioavailability studies in rats (50, 300, and 600 mg/kg, oral and subcutaneous), dogs (50, 150, and 450 mg/kg, oral and intravenous infusion), and humans (400 and 800 mg, oral) showed that the extent of oral absorption of potassium phosphanilate was low. The bioavailability, calculated by comparing the oral values for area under the plasma concentration curve with those for the respective parenteral doses, was 10% for rats and 45 (50 and 150 mg/kg) and 19% (450 mg/kg) for dogs. The 24-h urinary recovery also confirmed the low oral bioavailability, i.e., rat, 13 (oral) and 75% (subcutaneous); dog, 15 to 29 (oral) and 87% (intravenous) of the dose. Plasma levels and urinary recovery (4%, oral) were low and variable in humans. The poor absorption of oral doses may be due to drug precipitation in the stomach, low permeability of the soluble species due to extensive in situ ionization (pK
a
, 1.8 to 2) in the intestine, or first-pass metabolism to
N
-acetylphosphanilic acid. The plasma
t
½
values after parenteral administration were 0.3 h in rats and 1.3 h in dogs. Although the lack of adequate blood levels of phosphanilic acid after oral administration in humans precludes the use of this compound for treatment of systemic infections, the sustained urinary concentration at levels severalfold higher than the minimal inhibitory concentration (1 μg/ml) for at least 10 h postdose was indicative of the therapeutic usefulness in urinary tract infections.
High-pressure liquid chromatographic method for determination of rosaramicin in humans
Authors: Lin C , Kim H , Schuessler D , Oden E , Symchowicz S
Published: June 2012

A high-pressure liquid chromatographic method has been developed for the quantitative determination of rosaramicin in serum. This procedure involves addition of an internal standard, adjustment to alkaline pH, treatment with potassium carbonate, ether extraction, and a reverse-phase column separation with acetonitrile-acetate buffer mixture as the mobile phase. This technique produces a good linear relationship between the peak height ratio and the rosaramicin concentration. In addition, this method has proven to be quite specific for rosaramicin, since many of its derivatives tested do not interfere with the assay. The method is accurate and reproducible with a sensitivity of about 0.01 microgram of rosaramicin per ml of serum. It may be useful in monitoring drug levels in serum of patients and also for the pharmacokinetic studies of the drug in humans.
Penicillinase-producing Neisseria gonorrhoeae in the Netherlands: epidemiology and genetic and molecular characterization of their plasmids
Authors: van Embden J D , van Klingeren B , Dessens-Kroon M , van Wijngaarden L J
Published: June 2012

Penicillinase-producing Neisseria gonorrhoeae strains were isolated in the Netherlands with increasing frequency during the period of 1976 to 1979. About 3% of the gonococci isolated in the first half of 1979 produced penicillinase. In contrast to the period of 1976 to 1977, most penicillinase-producing N. gonorrhoeae infections during the period of 1978 to 1979 were contracted in the Netherlands. The results of genetic and molecular studies on 80 penicillinase-producing N. gonorrhoeae strains were similar to earlier observations of others: resistance plasmids of only two sizes, 4.5 and 3.3 megadaltons (Md), occurred in penicillinase-producing N. gonorrhoeae strains, and these encoded for the TEM-1 enzyme. The 4.5-Md plasmid could be transferred to Escherichia coli when it coexisted with a plasmid of 24 Md. The latter plasmid was present in the vast majority of the strains carrying the 4.5-Md plasmid. One strain carried a cryptic 7.5-Md plasmid in addition to the commonly found 2.5-Md plasmid. Two penicillinase-producing strains of Haemophilus parainfluenzae isolated were found to carry a 3.3-Md plasmid species which was indistinguishable from the 3.3-Md gonococcal resistance plasmids. No plasmid deoxyribonucleic acid was found in two strains of penicillinase-producing Branhamella catarrhalis, and these strains produced a penicillinase different from the TEM-1 enzyme.
Growth and antifungal homoazasterol production in Geotrichum flavo-brunneum
Authors: Rodriguez R J , Parks L W
Published: June 2012

The growth cycle and production of 15-aza-24-methylene-8, 14-cholestadiene-3 beta-ol (15-azasterol) in Geotrichum flavo-brunneum strain NRRL28804 have been studied. During the growth cycle of this organism, morphological changes were noted which corresponded to changes in the pH of the culture medium. A physiological shift from acid to base production also occurred during the growth cycle. Concomitant with this physiological shift was the synthesis of 15-azasterol. Upon synthesis of this azasterol, variations in the sterol pool were observed. These variations are identical to sterol alterations in susceptible yeast cells exposed to this drug (P. R. Hays, W. D. Neal, and L. W. Parks, Antimicrob. Agents Chemother. 12: 185-191, 1977.) It appears that NRRL28804 avoids growth inhibition from 15-azasterol by confining its production to late in the growth cycle.
Binding of beta-lactam antibiotics to penicillin-binding proteins of Staphylococcus aureus and Streptococcus faecalis: relation to antibacterial activity
Authors: Georgopapadakou N H , Liu F Y
Published: June 2012

The binding of 14 structurally diverse beta-lactam antibiotics to penicillin-binding proteins of Staphylococcus aureus and Streptococcus faecalis was studied, and the results were examined in the context of the antibacterial activity of the compounds. Penicillin-binding proteins 1 (molecular weight, 87,000) and 3 (molecular weight, 75,000) of S. aureus and penicillin-binding proteins 1 (molecular weight, 105,000) and 3 (molecular weight, 79,000) of S. faecalis bound beta-lactam antibiotics at concentrations comparable to minimum inhibitory concentrations and might therefore be essential. The low affinity of S. faecalis penicillin-binding proteins, relative to that of S. aureus penicillin-binding proteins, toward most beta-lactam antibiotics is probably responsible for the resistance of the former organism to most of these compounds.
Purification and properties of a cephalosporinase from Enterobacter cloacae
Authors: Minami S , Inoue M , Mitsuhashi S
Published: June 2012

A cephalosporin beta-lactamase (cephalosporinase) was extracted from Enterobacter cloacae GN7471 and purified by means of column chromatography. The resulting preparation gave a single protein band upon polyacrylamide gel electrophoresis. The enzyme's isoelectric point was 8.4, and its molecular weight was 44,000. The optimal pH was 8.5, and the optimal temperature was 40 degrees C. The enzyme hydrolyzed cephalosporins much more readily than penicillins. The enzyme activity was inhibited by iodine, semisynthetic penicillins, cefuroxime-type cephalosporins, and cephamycin derivatives. The enzymological properties of the purified enzyme were compared with those of beta-lactamases derived from other gram-negative enteric bacteria.
In vitro antagonism by erythromycin of the bactericidal action of antimicrobial agents against common respiratory pathogens
Authors: Cohn J R , Jungkind D L , Baker J S
Published: June 2012

Ten strains each of Staphylococcus aureus, Haemophilus influenzae, Enterobacter spp., Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, and Streptococcus pneumoniae were tested in vitro against erythromycin combined with ampicillin, cefamandole, or gentamicin. Antagonism by erythromycin occurred with 47% of the combinations involving strains of S. aureus and to a lesser degree with H. influenzae. Synergy occurred most commonly with H. influenzae (27%). The high frequency of antagonism and synergy with these organisms was associated with a broad range of bacteriostatic action by erythromycin against these same bacteria. The implications for the treatment of pneumonia are discussed.
Effect of meningitis and probenecid on the penetration of vancomycin into cerebrospinal fluid in rabbits
Authors: Krontz D P , Strausbaugh L J
Published: June 2012

This study examined the effects of experimental pneumococcal meningitis and probenecid administration on the penetration of parenterally administered vancomycin into cerebrospinal fluid in rabbits. Bacterial killing was also examined in infected animals. Meningitis was induced by intracisternal inoculation of Streptococcus pneumoniae. Vancomycin was administered in a loading dose followed by a continuous intravenous infusion for 6 h. Serum and cerebrospinal fluid samples were obtained at 0, 2, 4, and 6 h for antibiotic assays and quantitative cultures. Meningitis significantly enhanced the penetration of vancomycin into cerebrospinal fluid, but probenecid administration had no effect. In normal rabbits, at 6 h the mean percent penetration (cerebrospinal fluid concentration/serum concentration x 100%) +/- the standard deviation was 1.9 +/- 0.9% in the nonprobenecid group (n = 10) and 1.9 +/- 1.1% in the probenecid group (n = 9). In rabbits with experimental pneumococcal meningitis, the mean percent penetration at 6 h was 3.9 +/- 2.6% in the nonprobenecid group (n = 11) and 4.3 +/- 2.1% in the probenecid group (n = 9). Mean bacterial titers in the cerebrospinal fluid of infected animals decreased by more than 3.0 log 10 colony-forming units per ml in both the nonprobenecid and the probenecid groups.
Inhibition of peptidoglycan synthesis in ether-permeabilized Escherichia coli cells by structural analogs of D-alanyl-D-alanine
Authors: Pelzer H , Reuter W
Published: June 2012

Several analogs of D-alanyl-D-alanine have been proved to be competitive inhibitors of murein (cross-linked peptidoglycan) synthesis in either-permeabilized cells of Escherichia coli. Some analogs, distinguished from D-alanyl-D-alanine only by minor structural deviations, were incorporated into a murein-like sodium dodecyl sulfate-insoluble material in place of the natural substrate. These analogs therefore could be designated as competitive substrates of the cross-linked end product of murein synthesis. In contrast, others, even those containing bulky residues at the methyl group of the amino-terminal D-alanine, exhibited inhibition of murein synthesis. The last-mentioned group of analogs also inhibited a blank value which seems to be a characteristic feature of this system without added D-alanyl-D-alanine. From this data, a steady-state concentration of D-alanyl-D-alanine or D-alanine or both in growing cells of E. coli could be calculated as approximately 0.4 x 10(-3) M.
Two-hospital study of Staphylococcus aureus susceptibility to penicillin and ampicillin by Autobac I
Authors: Harris P C , Sealey L B
Published: June 2012

A total of 322 clinical isolates of Staphylococcus aureus were tested with ampicillin and penicillin G by Autobac I. Of these, 74 non-beta-lactamase-producing strains were isolated, of which only 32 were initially reported susceptible to both antibiotics by Autobac I. Thirty-two strains were ampicillin susceptible but penicillin resistant by Autobac I, and nine others were "resistant" to both antibiotics but had light-scattering index values that neared the "susceptible" breakpoints established by Pfizer Diagnostics for ampicillin and penicillin. Two strains were intermediate by disk diffusion test. A method was devised by which accurate results for non-beta-lactamase-producing S. aureus could be determined by Autobac I. Substitution of the 0.22-microgram ampicillin disk for the 0.2-U penicillin disk, coupled with extended incubation beyond the 3-h recommended interval, improved results. Alternative methods such as beta-lactamase enzyme assay or disk diffusion testing could be reserved for the occasional remaining cases of borderline light-scattering index-producing S. aureus (those nearing the susceptible break point, greater than or equal to 0.60). Substitution of the ampicillin disk coupled with extended incubation time did not result in reporting of false susceptibility for beta-lactamase-producing strains, a clinically hazardous situation.
Replacement of animal serum proteins by human albumin for growth and interferon production by Namalva cells
Authors: Field A K , Scattergood E M , Hopke C J , Tytell A A , Hilleman M R
Published: June 2012

Growth and interferon production by human lymphoblastoid cells (Namalva) have been achieved by using medium with a complete substitution of human albumin for fetal bovine serum. Medium containing 0.3% human albumin supported exponential cell growth (minimum doubling time, 20 h) in Bilthoven 10-liter fermentors. Interferon induction with Sendai virus resulted in interferon yields of 0.5 x 10(4) to 1.0 x 10(4) interferon units per 10(6) Namalva cells per ml in RPMI 1640 medium containing 0.15 to 0.3% human albumin. Both cell growth and interferon production in medium containing human albumin were comparable to growth and interferon production in the same medium containing 10 and 5% fetal bovine serum, respectively.
In Vitro Activity of Rosaramicin Against
Chlamydia trachomatis
Authors: Bowie W. R.
Published: June 2012

In vitro, rosaramicin was highly active against
Chlamydia trachomatis
when added to the culture system 1 or 48 h after inoculation with the chlamydia.
In vitro comparison of dibekacin and gentamicin activities
Authors: Hill C D , Counts G W , Turck M
Published: June 2012

Dibekacin, a new parenteral aminoglycoside, was compared with gentamicin in vitro against 221 clinical isolates. Tests for minimum inhibitory concentrations, performed in agar, demonstrated that dibekacin was comparable to gentamicin against most isolates tested. Dibekacin was slightly more active than gentamicin against some isolates of Pseudomonas aeruginosa, but was significantly less active against strains of Serratia.
Antibacterial and antifungal activities of benzimidazole and benzoxazole derivatives
Authors: Elnima E I , Zubair M U , Al-Badr A A
Published: June 2012

The in vitro antibacterial and antifungal activities of six benzimidazole and benzoxazole derivatives were tested against standard strains and 59 clinical isolates. Of the six compounds, only compounds II and III (both benzoxazoles) were active, whereas the rest were devoid of any activity. Considerable growth inhibition of all of the standard strains, including fungi and gram-positive and gram-negative bacteria, resulted when they were treated with these compounds. Fifty-nine clinical isolates of Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus were tested for susceptibility to the two compounds. The most susceptible were the S. aureus isolates. The two compounds were of comparable activity against all of the isolates, with compound III showing a slightly higher activity than compound II. Their respective minimal inhibitory concentrations for 90% inhibition of S. aureus were 25 and 50 microgram/ml. The gram-negative bacteria were resistant to the two compounds and required minimal inhibitory concentrations of 200 microgram/ml for a similar degree of inhibition.
Effects of penicillin on group A streptococci: loss of viability appears to precede stimulation of release of lipoteichoic acid
Authors: Kessler R E , van de Rijn I
Published: June 2012

The rate of killing of a group A streptococcal species by penicillin was compared with the release of lipoteichoic acid (LTA) and its deacylated derivative, dLTA. Although there was no stimulation of release from stationary-phase cells in the presence of penicillin, there was dramatic release of LTA and dLTA from exponential-phase cells after the addition of penicillin. Although decreases in viability were observed within 15 min after addition of penicillin, culture mass and LTA content did not appear to be affected until after 30 min. Stimulation of release of LTA and dLTA appeared to take place after 15 but before 30 min after addition of penicillin. These observations are interpreted to indicate that the stimulation of release of LTA and dLTA in response to penicillin is secondary to the killing event.
Anti-Pseudomonas activity in bronchial secretions of patients receiving amikacin or tobramycin as a continuous infusion
Authors: Mombelli G , Coppens L , Thys J P , Klastersky J
Published: June 2012

The penetration of amikacin and tobramycin into bronchial secretions and the resulting anti-Pseudomonas activity were assessed in two groups of tracheostomized or intubated patients with tracheobronchial infection and purulent bronchial secretions. The aminoglycosides were administered as continuous, high-dose intravenous infusions. The mean drug concentrations in serum and bronchial secretions were 12.8 and 2.0 microgram/ml for amikacin and 3.6 and 0.7 microgram/ml for tobramycin. The bronchial secretion/serum ratios varied over a wide range: from 9.6 to 22.8% (average, 14.9%) for amikacin and from 3 to 39.3% (average, 17.5%) for tobramycin. Sustained anti-Pseudomonas activities in bronchial secretions were achieved only in patients with very high aminoglycoside levels in serum. In most patients, however, no anti-Pseudomonas activity could be detected within bronchial secretions despite therapeutic levels of amikacin and tobramycin and adequate bactericidal activities in serum.
Efficacy of ampicillin therapy in experimental listeriosis in mice with impaired T-cell-mediated immune response
Authors: Bakker-Woudenberg I A , de Bos P , van Leeuwen W B , Michel M F
Published: June 2012

The importance of intact host defense mechanisms for successful antimicrobial therapy was investigated via a comparison of the activities of ampicillin against experimental Listeria monocytogenes infections in normal mice and congenitally athymic (nude) mice. Nude mice were used for these experiments because recovery from infection with this organism depends on development of cellular immunity induced specifically by a T-cell-mediated reaction. When infections ampicillin per mouse (32 doses of 25 mg each), which is twenty times the dose required for a cure of infections in normal mice (8 doses of 5 mg each), would not cure infections in nude mice. With a reduction in inoculum to 10(5) colony-forming units, cures were obtained with a total ampicillin dose of 800 mg (32 doses of 25 mg each), but not with 400 mg (16 doses of 25 mg each). These studies show clearly that the efficacy of ampicillin against infections with L. monocytogenes is dependent upon intact host defense mechanisms.
Sulfonamide and trimethoprim concentrations in human serum and skin blister fluid
Authors: Bruun J N , Ostby N , Bredesen J E , Kierulf P , Lunde P K
Published: June 2012

Various sulfonamides and trimethoprim were given orally twice a day to healthy volunteers. The drug concentrations in serum and tissue fluid from skin blisters were determined concomitantly. Maximal serum concentrations were obtained after 1 to 3 h. Absorption of sulfacarbamide and sulfadimidine was more rapid than for sulfadiazine, sulfamethoxazole, and trimethoprim. The penetration to blister fluid was delayed and maximal concentrations were usually reached after 4 to 8 h. The highest penetration to blister fluid was found for sulfacarbamide, sulfadiazine, and trimethoprim. During maintenance therapy sulfadiazine and trimethoprim gave blister fluid concentrations usually above 50% of the serum level. However, on the basis of dosage the highest sulfonamide concentration both in serum and blister fluid was obtained with sulfamethoxazole.
Inhibition of vaccinia virus maturation by zinc chloride
Authors: Katz E , Margalith E
Published: June 2012

Zinc chloride (0.1 mM) inhibited by 96.4% the growth of vaccinia virus in HeLa cells. Approximately 50% inhibition in formation of particles that sedimented in sucrose gradients similarly to vaccinia virions occurred in the presence of zinc ions. Whereas the synthesis of the viral deoxyribonucleic acid was not affected by zinc chloride, a decrease in the overall synthesis of viral polypeptides and inhibition of the cleavage of precursors to the core polypeptides were observed.
Moxalactam (LY127935) in treatment of meningitis due to gram-negative bacilli
Authors: Fisher J F , Carter M J , Parsons J , Rissing J P
Published: June 2012

Moxalactam (LY127935; 6059S), a new broad-spectrum beta-lactam antibiotic, was used successfully with an aminoglycoside in a patient with Serratia marcescens meningitis complicating a neurosurgical procedure. With a bioassay method, peak and trough serum and cerebrospinal; fluid concentrations of moxalactam were determined during therapy. Mean peak and trough serum levels were 100.6 and 35.5 micrograms/ml, respectively. Corresponding mean peak and trough cerebrospinal fluid levels were 12.4 and 10.38 micrograms/ml. Cerebrospinal fluid levels of moxalactam exceeded the minimal bactericidal concentration for the infecting organism by more than 30-fold throughout therapy. No untoward effects of moxalactam were observed. Moxalactam may be a useful agent in the treatment of meningitis due to susceptible gram-negative bacilli.
Comparative toxicity of amantadine hydrochloride and rimantadine hydrochloride in healthy adults
Authors: Hayden F G , Gwaltney J M , Van de Castle R L , Adams K F , Giordani B
Published: June 2012

The relative toxicities of amantadine and rimantadine were compared in a double-blind, placebo-controlled study involving healthy adults. In separate studies, drugs were administered at a dosage of 200 mg/day (52 volunteers) or 300 mg/day (196 volunteers) for 4.5 days. Both drugs were well tolerated at the lower dosage. At 300 mg/day amantadine recipients had a greater frequency and severity of central nervous system (nervousness, lightheadedness, difficulty concentrating) and sleep (insomnia, fatigue) complaints compared with rimantadine or placebo recipients. Amantadine recipients also performed less well on an objective test measuring sustained attention and problem-solving ability. Both amantadine and rimantadine recipients reported adverse gastrointestinal symptoms more often than placebo recipients. Because of better tolerance at higher dosage, rimantadine offers more promise than amantadine for treatment of influenza A virus infections.
Antibiotic resistance and R-factors in the fecal coliform flora of urban and rural dogs
Authors: Monaghan C , Tierney U , Colleran E
Published: June 2012

The incidence of antibiotic-resistant fecal coliforms in the rectal flora of 106 healthy dogs in the Galway area was investigated. As far as could be determined, none of the dogs had received antimicrobial drugs. Half of the dogs sampled were from homes within the city boundaries, whereas the remainder were from farms within a 40-mile (24.8-km) radius of the city. Of the dogs sampled, 47 had a highly susceptible fecal coliform flora, with less than 1% of the coliform population resistant to any of the four test antibiotics. Fecal coliforms resistant to one or more of the test drugs comprised between 40 and 100% of the total fecal coliform population of 36% of the rural dogs and 13% of the urban dogs sampled. Of the 473 resistant Escherichia coli isolates studied, the highest number of associated resistance determinants encountered was 5, with a medium number of 2.5. Of the E. coli isolates from rural dogs, 52% were resistant to three or more antibiotics compared with 37% of the isolates from urban dogs. A total of 64% of the isolates were shown to transfer some or all of their resistance determinants by conjugation. The transferability of ampicillin (77%) and chloramphenicol (70%) resistance determinants was higher than that of streptomycin (40%) or tetracycline (44%).
Properties of penicillin-binding proteins in Neisseria gonorrhoeae
Authors: Barbour A G
Published: June 2012

The properties of penicillin-binding proteins (PBPs) of Neisseria gonorrhoeae were studied by comparing PBPs of clinical isolates of different penicillin susceptibility and by putting various beta-lactam antibiotics in competition with radioactive penicillin for PBP binding. Apparent molecular weights of the three major PBPs found were 87,000 (PBP 1), 59,000 (PBP 2), and 44,000 (PBP 3). Relative penicillin resistance was associated with decreased binding to PBP 2 and, to a lesser extent, to PBP 1. Cephaloridine and benzylpenicillin, which produced spheroplasts at minimal inhibitory concentrations, bound to all three PBPs. In contrast, antibiotics which produced a majority of enlarged but apparently intact cells bound only to PBP 2 (mecillinam) or to PBPs 2 and 3 (cephalexin) at their minimal inhibitory concentrations.
Comparison of enzymatic and liquid chromatographic chloramphenicol assays
Authors: Weber A F , Opheim K E , Koup J R , Smith A L
Published: June 2012

A radioenzymatic assay and a "high-performance" liquid chromatographic assay for chloramphenicol were compared by using 52 patient specimens, 24 mock unknowns, and 13 quality control samples. Both methods were found to be rapid, precise, accurate, and sensitive, and either would be suitable for monitoring chloramphenicol concentrations in small volumes of serum. Linear regression analysis of serum chloramphenicol concentrations in patients receiving chloramphenicol succinate yielded a regression equation of Y = 1.04X + 0.274 (X = high-performance liquid chromatographic assay; Y = radioenzymatic assay), with a correlation coefficient of 0.971.
In vitro susceptibilities of Aeromonas hydrophila to 32 antimicrobial agents
Authors: Fass R J , Barnishan J
Published: June 2012

Minimal inhibitory concentrations of 32 antimicrobial agents for 20 strains fo Aeromonas hydrophila were determined by a microdilution method. Moxalactam was the most active drug tested. All strains were also susceptible to clinically achievable concentrations of mecillinam, cefamandole, cefuroxime, cefotaxime, aminoglycosides (except streptomycin), tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole.
Mezlocillin Susceptibility Tests by the Single-Disk Agar Diffusion Method
Authors: Fass Robert J. , Prior Richard B.
Published: June 2012

A regression line for correlating zones of inhibition of a 75-μg mezlocillin disk with minimal inhibitory concentrations of mezlocillin for
Enterobacteriaceae
and nonfermenters was calculated. Correlation was excellent (
r
= −0.96) for all species tested except
Pseudomonas cepacia
.
Permeability and Susceptibility of
Escherichia coli
to β- Lactam Compounds
Authors: Clark David
Published: June 2012

In general, the susceptibility of envelope mutants of
Escherichia coli
to β-lactam compounds correlates well with the permeability of these antibiotics through the outer membrane. However, several mutants were isolated which, although apparently freely permeable to penicillins, showed only marginal increases in susceptibility to these agents.
In vitro activity of naftifine, a new antifungal agent
Authors: Georgopoulos A , Petranyi G , Mieth H , Drews J
Published: June 2012

Naftifine exhibits an interesting in vitro spectrum of activity against dermatophytes (38 strains; minimal inhibitory concentration [MIC] range 0.1 to 0.2 microgram/ml), aspergilli (6 strains; MIC range, 0.8 to 12.5 microgram/ml), Sporothrix schenckii (2 strains; MICs, 0.8 and 1.5 microgram/ml), and yeasts of the genus Candida (77 strains; MIC range, 1.5 to greater than 100 microgram/ml). Its degree of efficacy is unaffected by the organism density in the test medium, and it is primarily fungicidal against dermatophytes as well as yeasts. Its in vitro efficacy is pH dependent and rises with increasing pH values.
Antibacterial activity of ceftriaxone (Ro 13-9904), a beta-lactamase-stable cephalosporin
Authors: Neu H C , Meropol N J , Fu K P
Published: June 2012

The in vitro activity of ceftriaxone (Ro 13-9904), a parenteral cephalosporin, was compared with that of other beta-lactam antibiotics. the compound was less active against Staphylococcus aureus and Staphylococcus epidermidis than was cephalothin or cefamandole, but it was comparable to cefoxitin, cefotaxime, and moxalactam in inhibiting most isolates of S. aureus at 3.1 microgram/ml. Ro 13-9904 inhibited Streptococcus pyogenes and Streptococcus pneumoniae at concentrations below 0.25 microgram/ml, but Streptococcus faecalis required concentrations above 25 microgram/ml. Neisseria gonorrhoeae and Haemophilus influenzae were inhibited at concentrations similar to those of cefotaxime, less than 0.1 microgram/ml. Ro 13-9904 was as active as cefotaxime and moxalactam against most Enterobacteriaceae and was the most active agent tested against Proteus, inhibiting all strains tested at 0.006 microgram/ml. Ro 13-9904 was slightly less active than moxalactam or cefoxitin against Bacteroides fragilis, requiring more than 100 microgram/ml to inhibit 90% of isolates, and it was less active than cefoperazone against Pseudomonas aeruginosa. Presence of serum, alteration of pH, and use of various media did not change the inhibitory levels. Bactericidal concentrations were similar to inhibitory levels. Ro 13-9904 was stable to most plasmid-mediated beta-lactamases, but was hydrolyzed by some Enterobacter, Proteus, and Bacteroides beta-lactamases of chromosomal origin.
Development and validation of a neutralizer system for in vitro evaluation of some antiseptics
Authors: Sheikh W
Published: June 2012

A neutralizer system was developed and validated for use in the in vitro bactericidal evaluation of three commonly used antiseptics, namely, Hibiclens (4% [wt/vol] chlorhexidine gluconate), Betadine (7.5% [wt/vol] povidone-iodine), and pHisoHex (3% [wt/vol] hexachlorophene). The neutralizer finally selected after a screening of 12 potential candidates consisted of 3% Asolectin, 10% Tween 80, and 0.3% sodium thiosulfate in the recovery agar. This neutralizer system was tested and validated for its neutralizing capacity for the three antiseptics, as well as for its lack of inherent bactericidal action against Staphylococcus aureus and a number of gram-negative bacteria of clinical significance, With no more than a 10-fold dilution of the antiseptic, the selected neutralizer system was 100% effective in neutralizing all the bacteriostatic carry-over of the three antiseptics and was also completely without any inherent bactericidal action against all the test organisms used. Sodium sulfite (considered to be a potential inactivator for iodophores such as Betadine), even in concentrations as low as 0.1%, was found to be ineffective or inherently bactericidal, whereas 0.3% sodium thiosulfate, in combination with Asolectin and Tween 80, was adequate (effective as well as non-bactericidal) and was considered to be essential for the neutralization of the three test antiseptics, namely, Hibiclens, Betadine, and pHisoHex.
Comparative in vitro studies of Ro 13-9904, a new cephalosporin derivative
Authors: Eickhoff T C , Ehret J
Published: June 2012

The in vitro activity of Ro 13-9904, a new cephalosporin derivative, was compared with the activities of cephalothin, cefamandole, cefoxitin, cefotaxime, and moxalactam against 591 clinical isolates of gram-negative and gram-positive organisms. The spectra of activity and potency of Ro 13-9904 and cefotaxime were quite similar; they were the most active agents against Enterobacteriaceae, Streptococcus pyogenes, Haemophilus influenzae, Neisseria gonorrhoeae, and Neisseria meningitidis. Moxalactam was only slightly less active against these organisms. Ro 13-9904, cefotaxime, and moxalactam were approximately equal in activity against Pseudomonas aeruginosa; concentrations of 50 to 100 microgram/ml inhibited over 90% of the strains tested. Cefamandole and cephalothin were the most active drugs tested against staphylococci. Moxalactam demonstrated the highest intrinsic activity against Bacteroides fragilis; a concentration of 1.6 microgram/ml inhibited over 50% of the strains. All six of the antibiotics were essentially inactive against group D streptococci. The action of all of the antibiotics was bactericidal, with minimal bactericidal concentrations generally being no more than twofold greater than minimal inhibitory concentrations. The only exception to this was found when large inocula of Staphylococcus aureus were tested. Increased inoculum size generally sharply reduced the activity of Ro 13-9904, cefotaxime, and moxalactam against Enterobacteriaceae and P. aeruginosa.