bluuebunny/crossref_metadata_2025 huggingface dataset:
Antimicrobial Susceptibility and Selection of Resistance Among
Staphylococcus epidermidis
Isolates Recovered from Patients with Infections of Indwelling Foreign Devices
Authors: Archer Gordon L.
Published: June 2012

Twenty-seven isolates of
Staphylococcus epidermidis
from patients with prosthetic valve endocarditis or infected cerebrospinal fluid shunts were examined for susceptibility to antimicrobial agents. Subpopulations resistant to 20 and 100 μg of methicillin per ml were present in 63% of the isolates (methicillin-resistant isolates). Subpopulations resistant to 20 μg of nafcillin and cephalothin per ml were found in every methicillin-resistant isolate but with frequencies (10
−5.0 ± 0.5
and 10
−6.4 ± 0.9
, respectively) which were not always detectable by susceptibility testing. Resistance to ≥1.6 μg of penicillin per ml was found in 80% of isolates. Cephalothin, cefazolin, and cefamandole were more active than cefoxitin or cephradine, and gentamicin was more active than tobramycin or amikacin; rifampin was the single most active agent against all isolates. There was no difference in susceptibility between prosthetic valve endocarditis and cerebrospinal fluid shunt infection isolates. Among methicillin-resistant isolates, the phenotypic expression of resistance to methicillin or nafcillin but not to cephalothin could be enhanced by 48 h of incubation with each drug. Isolates containing no methicillin-resistant subpopulations were killed by incubation with methicillin, nafcillin, or cephalothin. High-level resistance to rifampin emerged in both methicillin-resistant and methicillin-sensitive isolates after 8 to 24 h of incubation with this drug. The presence or absence of antibiotic-resistant subpopulations among
S. epidermidis
isolates and their selection during treatment should be considered when therapy is devised.
Nonvalue of Neomycin Instillation after Intermittent Urinary Catheterization
Authors: Haldorson Alice M. , Keys Thomas F. , Maker Myron D. , Opitz Joachim L.
Published: June 2012

This study evaluated weekly urine cultures of patients with neurogenic bladder disease who underwent intermittent urinary catheterization for bladder retraining. One group of 53 patients in 1974 received regular instillations of 0.1% neomycin after each catheterization. A similar group of 55 patients in 1975 did not receive neomycin and constituted a control group. Distribution of age, sex, diagnosis, and duration of bladder retraining was comparable in both groups. Quantitative bacterial colony counts of 10
4
to 10
5
or greater per ml of urine were considered significant. There was no difference in the incidence of bacteriuria between the neomycin-treated group and the control group (53 versus 49%, respectively), and most patients in each group had colony counts >10
5
/ml.
Escherichia coli
was seen less frequently in neomycin-treated patients (43.4 versus 62.5%), but a greater percentage of infections due to
Pseudomonas aeruginosa
, group D streptococci, and yeasts was noted in the neomycin-treated group than in the control group (41.5 versus 22.5%).
Inactivation of Metronidazole by Anaerobic and Aerobic Bacteria
Authors: Ralph E. D. , Clarke Denise A.
Published: June 2012

The rate of inactivation of metronidazole in vitro was determined during the course of time-kill curves against anaerobic and aerobic bacteria in the stationary phase of growth. Metronidazole at a concentration of 10 μg/ml, as measured by bioassay, was rapidly inactivated in broth culture by susceptible anaerobic bacteria (minimum bactericidal concentration ≤ 3 μg/ml), and this correlated closely with its bactericidal activity. In contrast, the drug was neither inactivated nor had any bactericidal activity against a resistant strain of
Propionibacteriumacnes
(minimum bactericidal concentration > 1,500 μg/ml). Three of four aerobic bacteria also inactivated metronidazole, although at generally slower rates than the anaerobes, but this was not associated with a bactericidal effect against these organisms. The presence of aerobic bacteria in mixed cultures with
Bacteroides fragilis
did not, moreover, inhibit the bactericidal activity of metronidazole against the latter organism. However, the possibility still remains that, in vivo, aerobic bacteria capable of inactivating metronidazole could inhibit the action of the drug against anaerobes in mixed infections.
Susceptibility of Anaerobic Bacteria to Sulfamethoxazole/Trimethoprim and Routine Susceptibility Testing
Authors: Wüst Jürg , Wilkins Tracy D.
Published: June 2012

The minimal inhibitory concentrations (MICs) of sulfamethoxazole and trimethoprim against 144 strains of obligately anaerobic bacteria were determined on Diagnostic Sensitivity Test agar (Oxoid) or in prereduced Diagnostic Sensitivity Test broth, both supplemented with sodium pyruvate (1 mg/ml), hemin (5 μg/ml), and vitamin K
1
(1 μg/ml). Fifty-eight percent of the strains were susceptible to sulfamethoxazole alone (MIC ≤ 16 μg/ml), only 12% were susceptible to trimethoprim alone (MIC ≤ 1 μg/ml), and 85% were susceptible to the combination of sulfamethoxazole plus trimethoprim (MIC ≤ 16 μg/ml) at a ratio of 19:1. All 45 strains of the
Bacteroides fragilis
group were susceptible to the combination. Synergy of the combination was often observed by a checkerboard MIC determination of 123 strains, usually most markedly when the ratio of the two components was near 1:1. However, there was also synergism at the ratio of sulfamethoxazole to trimethoprim of 16:1 in 61 (53.5%) of the 114 strains that could be evaluated for synergistic activity. When the strains were tested by the broth-disk test proposed by Wilkins and Thiel, modified by using prereduced Diagnostic Sensitivity Test broth instead of brain heart infusion broth and by using a smaller inoculum, there was over 90% correlation with the MICs. Poor results were found when the broth-disk tests were performed in brain heart infusion broth. There was very poor correlation between inhibition zone diameters by an agar diffusion method and MICs.
Single-Dose Doxycycline for Cholera
Authors: Sack David A. , Islam Sirajul , Rabbani Hassan , Islam Asma
Published: June 2012

To determine the efficacy of single-dose doxycycline in the treatment of cholera, we carried out a randomized prospective trial in 65 patients. Treatment consisted of either a single dose of 200 mg of doxycycline (or 4 mg/kg in patients less than 15 years old) or multiple doses of doxycycline, 500 mg over 4 days (or 10 mg/kg in patients less than 15 years old). There were no differences between the groups in the volumes of intravenous fluid required, volumes of diarrheal stool, or durations of diarrhea. The mean duration of positive stool cultures for
Vibrio cholerae
was similar for the two groups, although in both groups several patients continued to excrete Vibrios in the stool for more than 3 days. Blood levels of antibiotic demonstrated that the doxycycline was absorbed in spite of the rapid transit time associated with severe diarrhea. These results suggest that although tetracycline remains the drug of choice for cholera, doxycycline is a reasonable alternative, and that a single dose of 200 mg (4 mg/kg in children) is effective clinically.
Resistance of Spheroplasts and Whole Cells of
Pseudomonas cepacia
to Polymyxin B
Authors: Manniello Jane M. , Heymann Hans , Adair Frank W.
Published: June 2012

Sucrose-lysozyme spheroplasts were prepared from two strains of
Pseudomonas cepacia
and tested for susceptibility to polymyxin B and benzalkonium chloride. Spheroplasts were more susceptible than whole cells to benzalkonium chloride but not to polymyxin B. Disruption of the outer membrane layer was not by itself sufficient to render
P. cepacia
susceptible to polymyxin B.
Prediction of Cefazolin Penetration into High- and Low-Protein-Containing Extravascular Fluid: New Method for Performing Simultaneous Studies
Authors: Peterson Lance R. , Gerding Dale N.
Published: June 2012

The effect of extravascular fluid protein concentration and drug-protein binding was studied in rabbits with subcutaneously implanted Visking chambers. Chambers containing serum or saline were simultaneously studied in three animals by injecting cefazolin (30 mg/kg) intramuscularly every 4 h for four doses. Five additional animals were then studied for an 8-h period while receiving two doses of cefazolin. Peak and trough serum and chamber fluid were assayed for cefazolin concentration. The three-animal experiment demonstrated that equilibrium in the subcutaneous chambers was reached after two intramuscular injections and that the extravascular fluid levels were stable in comparison to the wide fluctuation of the serum levels. The five-animal experiment demonstrated that after two doses the serum-filled chambers contained 12.9 μg of cefazolin per ml, whereas saline-filled chambers contained 1.8 μg of cefazolin per ml. Ratios of chamber to peak serum for the second study were 12.4% for serum chambers and 1.7% for saline chambers. The cefazolin concentration in high-and low-protein extravascular fluid in both studies could be predicted from the logarithmic mean of the peak and trough serum cefazolin concentration and the antibiotic binding to rabbit serum and extravascular fluid proteins. These observations explain the previously published apparent discrepancies seen in studies of extravascular penetration of highly protein-bound antibiotics such as cefazolin.
Comparison of the In Vitro Activity of Bay k 4999 and Piperacillin, Two New Antipseudomonal Broad-Spectrum Penicillins, with Other β-Lactam Drugs
Authors: Wise R. , Andrews J. M. , Bedford K. A.
Published: June 2012

Bay k 4999 and piperacillin, two new substituted ampicillins, were compared with other β-lactam antibiotics, including carbenicillin, azlocillin, mezlocillin, benzylpenicillin, ampicillin, and cefoxitin, against a wide range of gram-positive and -negative organisms. Bay k 4999 and piperacillin were extremely active against
Pseudomonas aeruginosa
(50% inhibited by 2 μg/ml), being about 16-fold more active than carbenicillin. Bay k 4999 was the most active drug against
Escherichia coli
(50% inhibited by 0.5 μg/ml) and
Klebsiella
spp. (50% inhibited by 2 μg/ml). Piperacillin and Bay k 4999 were equally active against
Proteus
spp., and piperacillin had high activity against
Bacteroides fragilis
(50% inhibited by between 1 and 2 μg/ml).
Antiviral Activity of Intranasally Applied Human Leukocyte Interferon
Authors: Greenberg Stephen B. , Harmon Maurice W. , Johnson Paul E. , Couch Robert B.
Published: June 2012

Previous studies in our laboratory have demonstrated that the development of antiviral activity of human leukocyte interferon (IF) in nasal epithelial cells is time and concentration dependent and that the loss of intranasally applied human leukocyte IF is rapid. The present studies compared the activity of IF applied intranasally either by nasal drops or by a saturated cotton pledget. Adult volunteers had IF applied to an area of nasal mucosa (2 by 2 cm
2
) either by repeated nose drops or by a saturated cotton pledget that was applied to the nasal mucosa and left in place for 1 h. Nasal epithelial cells scraped from the area of application, as well as the control, untreated side of the same volunteers, were challenged with vesicular stomatitis virus. No significant reduction in mean virus yield was found in volunteers who received 80,000 U by nose drops. Significant reduction (
P
< 0.025) in mean virus yield was found in cells obtained 4 h after 80,000, 50,000, or 20,000 U was applied by cotton pledget or in volunteers pretreated with oral antihistamines prior to receiving 80,000 U by nose drops. These experiments indicate that nasal epithelial cells can be made antiviral in vivo by application of human leukocyte IF. However, practical usefulness of human leukocyte IF for prophylaxis against respiratory viral infections may depend on the method of local application.
Comparative In Vitro Activity of Newer Cephalosporins Against Anaerobic Bacteria
Authors: Chow Anthony W. , Bednorz Dominick
Published: June 2012

The in vitro susceptibilities of 408 recent clinical isolates of anaerobic bacteria against cefaclor, cephalexin, cephalothin, cefazolin, cefamandole, and cefoxitin were compared by an agar dilution technique. Against gram-positive bacteria, especially peptococci, peptostreptococci, and propionibacteria, cephalexin and cefaclor were significantly less active than cephalothin (
P
< 0.05). Cephalexin was also less active than cephalothin against clostridia and lactobacillus (
P
< 0.05). Against gram-negative bacteria, major differences were observed primarily with
Bacteroides fragilis
, against which cephalexin, cefazolin and cefoxitin were all significantly more active than cephalothin (
P
< 0.001). At concentrations of 16 μg per ml, however, all cephalosporins showed high in vitro activity, except against
Lactobacillus
species and
B. fragilis
. Cephalothin, cefazolin and cefamandole were considerably more active against the former, whereas cefoxitin was distinctly more active against the latter.
Evaluation of Virucidal Compounds for Inactivation of Rhinovirus on Hands
Authors: Hendley J. Owen , Mika Leonard A. , Gwaltney Jack M.
Published: June 2012

Antimicrobial liquids and foams were applied to the hands to determine their virucidal activity against rhinoviruses. Dilute solutions (1%) of iodine in ethyl alcohol or in water were most effective in causing inactivation of rhinovirus when applied immediately after viral contamination. Iodine also had a residual virucidal activity which persisted on the hands for up to 1 h. Less effective inactivation of rhinovirus was observed with foams containing 0.23% hexachlorophene and 58% ethyl alcohol and another containing 0.2% benzalkonium chloride and 50% ethyl alcohol. Ethyl alcohol alone or in a mixture with benzyl alcohol was the least effective preparation tested.
Reversible Effects on Cellular Metabolism and Proliferation by Trisodium Phosphonoformate
Authors: Stenberg Kjell , Larsson Alf
Published: June 2012

The antiviral compound trisodium phosphonoformate (PFA), which inhibits herpesvirus multiplication by 50% at a concentration of 10 μM, did not show any effects on macromolecular synthesis and cell proliferation in HeLa and human lung cells at this concentration. At the high concentration of 2 mM, PFA reduced DNA synthesis to 50% after 1 h of treatment, whereas no effects could be seen on RNA and protein synthesis. Treatment for 24 h with 1 mM PFA inhibited both DNA synthesis and cell proliferation to 50%. The inhibition of DNA synthesis and cell proliferation at 10 mM PFA was rapidly reversed by removing the drug from the cells.
Genetic and Molecular Characterization of an
Escherichia coli
Plasmid Coding for Hydrogen Sulfide Production and Drug Resistance
Authors: Jones Randall T. , Thai Le P. , Silver Richard P.
Published: June 2012

An H
2
S-producing variant of
Escherichia coli
(strain 142) isolated from a urinary tract infection was found to be resistant to high levels of tetracycline, ampicillin, streptomycin, and sulfonamide. The H
2
S trait segregated spontaneously at a frequency of 2.5 × 10
−3
. No segregation was observed for the drug resistance determinants. Neither ethidium bromide nor acridine orange affected the rate of segregation of the drug resistance determinants or the trait for H
2
S production. Antibiotic resistance and hydrogen sulfide production were conjugally transferred to
E. coli
K-12 recipients at a frequency of approximately 10
−5
per donor cell. Antibiotic resistance and hydrogen sulfide production were also transduced as a single unit with phage P1L4. Genetic data, based on the segregation of resistance determinants and the H
2
S trait among transconjugant and transductant classes, suggested the presence of two R plasmids. Plasmid DNA was isolated by cesium chloride-ethidium bromide centrifugation. Two plasmid species were detected by agarose gel electrophoresis of purified plasmid DNA, a large molecule of about 80 × 10
6
daltons (designated pSR12) and a small molecular species of approximately 5.5 × 10
6
daltons (designated pSR13). Transformation studies using purified plasmid DNA showed that the large pSR12 plasmid confers resistance to ampicillin, tetracycline, and streptomycin and also carries the gene(s) for H
2
S production. The small pSR13 plasmid confers resistance to streptomycin and sulfonamide.
In Vitro Activity of Sch 21420, Derivative of Gentamicin B, Compared to That of Amikacin
Authors: Kabins Sherwin A. , Nathan Catherine
Published: June 2012

The minimal inhibitory concentration of Sch-21420 closely paralleled amikacin for 125 strains of aerobic gram-negative bacilli and
Staphylococcus aureus
primarily selected for testing because of resistance to other aminoglycoside antibiotics. Fifteen of 26 strains requiring 20 μg or more of amikacin per ml for inhibition were inhibited by two- to fourfold less Sch 21420. The majority of organisms resistant to both agents owed their resistance to mechanisms other than the carriage of aminoglycoside-modifying enzymes. Most strains carrying aminoglycoside 6′-acetyltransferase, capable of modifying amikacin, were susceptible to 10 μg or less of Sch 21420 per ml.
Piperacillin: Human Pharmacokinetics After Intravenous and Intramuscular Administration
Authors: Tjandramaga T. B. , Mullie A. , Verbesselt R. , De Schepper P. J. , Verbist L.
Published: June 2012

The pharmacokinetics of piperacillin were studied in a total of 26 Caucasian normal male volunteers. Single intramuscular doses of 0.5, 1.0, and 2.0 g were given to three groups, each containing eight volunteers. Mean peak serum concentrations of 4.9, 13.3, and 30.2 μg/ml were assayed at 30 to 50 min, and measurable levels were present up to 4, 6, and 8 h, respectively, after dosing. Single intravenous bolus doses of 1.0, 2.0, 4.0, and 6.0 g were given to four groups of five subjects, and mean serum concentrations of 70.7, 199.5, 330.7, and 451.8 μg/ml were measured at the end of the injections. The antibiotic had a mean terminal serum half-life of 60 to 80 min after the intramuscular doses and 36 to 63 min after intravenous administrations, depending on the dose. The apparent distribution volume was 20 to 24 liters/1.73 m
2
, and distribution volume at steady state was 16 to 19 liters/1.73 m
2
. Mean urinary recovery in 24 h was 74 to 89% for the intravenous doses and 57 to 59% for the intramuscular doses. The piperacillin-creatinine clearance ratios indicated that the proportion of renal excretion of piperacillin through tubular secretion was 56 to 73%, and this was confirmed by the renal clearance data from eight volunteers receiving probenecid treatment before the piperacillin dose. Probenecid (1 g given orally before administration of piperacillin) increased peak serum concentration by 30%, terminal serum half-life by 30%, and the area under the plasma concentration curve by 60%, and it decreased the apparent distribution volume by 20% and the renal clearance of the intramuscularly administered (1 g) antibiotic by 40%. Injections of piperacillin by both parenteral routes were well tolerated.
Effect of 9-(2-Hydroxyethoxymethyl)guanine on Herpesvirus-Induced Keratitis and Iritis in Rabbits
Authors: Kaufman Herbert E. , Varnell Emily D. , Centifanto Ysolina M. , Rheinstrom Stephen D.
Published: June 2012

Drugs used for the inhibition of DNA viruses, such as iododeoxyuridine, adenine arabinoside, or trifluorothymidine, are not biochemically selective in their action and also interfere with normal cellular functions. The recently reported 9-(2-hydroxyethoxymethyl)guanine (acycloguanosine) is selectively phosphorylated by viral thymidine kinase but not by normal cellular thymidine kinase. Our present studies show that the acycloguanosine is as effective in treating herpetic keratitis in the rabbit as iododeoxyuridine and trifluorothymidine when given topically as an ointment. It is also effective when given intravenously for the treatment of herpetic iritis and is effective in preventing death from encephalitis in rabbits.
Assay of Gentamicin and Tobramycin in Sera of Patients by Gas-Liquid Chromatography
Authors: Mayhew James W. , Gorbach Sherwood L.
Published: June 2012

Therapeutic levels of gentamicin and tobramycin in the sera of patients were measured by gas-liquid chromatography. Concentration-response curves for both drugs were linear over an expected therapeutic range of 1.3 to 12.5 μg/ml (coefficient of determination was >0.97). Coefficients of variation for chromatographic response to gentamicin varied from 6.3 to 9.6%, and to tobramycin from 3.8 to 13.5%. Paired gas-liquid chromatography and microbiological assays for patient serum aminoglycoside levels were performed on 106 gentamicin and 40 tobramycin sera. At levels <2.0 μg/ml, the average difference of estimates between the two assay techniques for gentamicin and tobramycin were, respectively, 38 and 29%. At drug concentrations >2.0 μg/ml, the mean difference between paired estimates was near 20% for both aminoglycosides. The speed, precision, and accuracy of the gas-liquid chromatography assay indicate that it can be a useful alternative to the microbiological procedure for the determination of gentamicin and tobramycin levels in human serum.
Purification and Properties of a Bacteriocin-Like Substance (Acnecin) of Oral
Propionibacterium acnes
Authors: Fujimura Setsuo , Nakamura Takeshi
Published: June 2012

Propionibacterium acnes
CN-8, isolated from human dental plaque, was grown in a liquid medium, and its bacteriocin-like substance (acnecin) was extracted from the cells by ultrasonic treatment. Acnecin was purified to a homogeneous state with recovery of 47%. Specific activity increased 72-fold in comparison with the crude extract. The properties of acnecin were as follows. (i) Acnecin may consist of five subunits with a molecular weight of about 12,000. (ii) Its isoelectric point was 5.5. (iii) In amino acid composition, aspartic acid, glutamic acid, glycine, and alanine were predominant, whereas cystine was not present. (iv) Acnecin contained 3.3% carbohydrate but was substantially free from lipid. (v) The activity was lost by heating at 60°C or by protease and lysozyme treatments. Acnecin acted bacteriostatically on the indicator strain without killing it. The action spectrum of acnecin was very narrow; it was effective only against strains of non-acnecin-producing
P. acnes
and
Corynebacterium parvum
, a species closely related to
P. acnes
.
Comparative Evaluation of Piperacillin in Vitro
Authors: Dickinson Gordon M. , Cleary Timothy J. , Hoffman Thomas A.
Published: June 2012

The minimal inhibitory concentrations of piperacillin and seven other betalactam antibiotics were determined against 407 bacterial isolates. Piperacillin was found to be more active than ampicillin against susceptible gram-negative bacilli and more active than either carbenicillin or ticarcillin against
Pseudomonas aeruginosa
and streptococci. Although piperacillin was active against
Klebsiella pneumoniae
, this activity was less than that of the cephalosporins. Piperacillin was not active against penicillin-resistant
Staphylococcus aureus
and
Enterobacteriaceae
that were resistant to the other test antibiotics.
Antiviral and Interferon-Inducing Properties of 1,5-Diamino Anthraquinones
Authors: Stringfellow D. A. , Weed S. D. , Underwood G. E.
Published: June 2012

A series of anthraquinones with amino substituents at the 1,5 positions were found to induce interferon in mice. A prototype compound, 1,5-bis[(3-morpholinopropyl)amino]-anthraquinone (Ia), was an effective antiviral agent when administered either orally or parenterally. Peak interferon titers were found 12 to 24 h after drug treatment. The minimum oral dose of Ia required to induce serum interferon or to protect mice against a lethal virus infection was 62 mg/kg. Mice tolerated an oral dose of at least 30 times this minimum effective dose. A single dose of Ia given up to 6 days prior to infection had significant protective activity. Biological properties of Ia were compared with those of three other 1,5-diamino anthraquinones, which also induced interferon and demonstrated antiviral activity in mice. The most active compound was 1,5-bis[[2-(diethylamino)ethyl]amino]-anthraquinone (Ib), which protected mice against virus infection at a dose as low as 8 mg/kg (less than 1/60 its maximum tolerated dose). Mice developed hyporeactivity to interferon induction if the same inducer was injected daily, although by alternating between different inducers the loss of interferon responsiveness could be avoided.
SCE-963, a New Potent Cephalosporin with High Affinity for Penicillin-Binding Proteins 1 and 3 of
Escherichia coli
Authors: Nozaki Yukimasa , Imada Akira , Yoneda Masahiko
Published: June 2012

A few biochemical activities of SCE-963, a new cephalosporin with potent antibacterial activities against gram-negative bacteria, were compared with those of several currently available cephalosporins against strains of
Escherichia coli
K-12. The minimum inhibitory concentrations of SCE-963, cefazolin, cephaloridine, cephalothin, and cephalexin were 0.2, 1.56, 3.13, 12.5, and 25 μg/ml, respectively. Affinities of these cephalosporins for the penicillin-binding protein (PBP) 1B of
E. coli
correlated well with their antibacterial activities; among tested cephalosporins, SCE-963 showed the highest affinity for PBP 1B. SCE-963 inhibited cross-linking of peptidoglycan in a cell-free system the most strongly suggesting that this inhibition results from its high affinity for PBP 1B. SCE-963 also showed the highest affinity for PBP 3; it caused filamentation of cells over a wide range of relatively lower concentrations. Thus its superior antibacterial activity is believed to be manifested through its high affinity for the PBPs.
Protection from Gentamicin Nephrotoxicity by Cephalothin and Carbenicillin
Authors: Bloch Richard , Luft Friedrich C. , Rankin Laura I. , Sloan Rebecca S. , Yum Moo Nahm , Maxwell Douglas R.
Published: June 2012

In rats, cephalothin exerts a protective effect upon the nephrotoxicity of gentamicin. To examine the possibility that this effect is also observed with carbenicillin, we gave the following (milligrams per kilogram) to rats daily for 14 days: gentamicin alone, 60; gentamicin plus cephalothin, 100, 500, or 1,000; gentamicin plus carbenicillin, 50, 100, 250, 500, or 1,000. A 500-mg/kg dose of cephalothin afforded significant partial protection from gentamicin nephrotoxicity, as did a 100-mg/kg dose of carbenicillin. Increasing doses of either drug failed to increase protection. The data suggest that in rats not only does carbenicillin afford some protection from gentamicin nephrotoxicity, but also that it does so at a lower dose than cephalothin. These findings may in part explain the divergent observations regarding the nephrotoxicity of cephalothin-gentamicin combination therapy in rats and humans.
Netilmicin in Gram-Negative Bacterial Infections
Authors: Snydman David R. , Tally Francis P. , Landesman Sheldon H. , Barza Michael , Gorbach Sherwood L.
Published: June 2012

Netilmicin, a new semisynthetic aminoglycoside, was used in the treatment of 42 patients with serious gram-negative bacterial infections. Of the 40 evaluable patients, 24 (60%) were cured, and 8 (20%) had a favorable clinical response, for a total clinical response rate of 80%. Eight patients failed to respond; of these, three had undrained abscesses and two had severe granulocytopenia. Three of the patients who failed had organisms in which resistance to netilmicin developed during therapy, and in two of these three netilmicin was the only aminoglycoside to which resistance developed. Of the 37 patients evaluable for toxicity, 8 (22%) developed renal insufficiency. Two patients had mild but persistant elevation in serum creatinine. Three patients had nephrotoxicity while on gentamicin in the past. Pre- and posttherapy audiograms were done on 26 patients; none had hearing loss. Four patients had mild, transient asymptomatic elevations in alkaline phosphatase. The pretreatment clinical isolates were tested for in vitro susceptibility. The median minimal inhibitory concentration of netilmicin, gentamicin, and tobramycin ranged between 0.5 and 2 μg/ml. The median minimal inhibitory concentration of amikacin was approximately twofold higher. No clear in vitro superiority of one aminoglycoside over another was observed.
Extreme Sensitivity of Enveloped Viruses, Including Herpes Simplex, to Long-Chain Unsaturated Monoglycerides and Alcohols
Authors: Sands Jeffrey , Auperin David , Snipes Wallace
Published: June 2012

Unsaturated monoglycerides and alcohols of chain lengths of 16 or 18 carbons were found to be extremely potent inactivators of two enveloped viruses, herpes simplex virus type 2 and bacteriophage φ6. The lipid-containing bacteriophage PM2 was also inactivated by some of these amphiphilic molecules. Treatment of herpes simplex virus type 2 with these compounds at concentrations as low as 0.2 μM reduced virus survival to 50% in 30 min, making these agents the most potent inactivators of herpes simplex viruses discovered that are not cytotoxic to mammalian cells. Detailed characterizations of the effects of unsaturated monoglycerides and alcohols on bacteriophages φ6 and PM2 showed that the inactivated φ6 virion remained nearly intact but that PM2 was almost completely disrupted by the inactivating treatment. Some of the compounds inactivate the viruses even at low temperature (0°C). Excess amounts of diglycerides and phospholipids interfere with the inactivating abilities of some of the unsaturated monoglycerides and alcohols against φ6 and PM2. Our findings suggest that the unsaturated monoglycerides and some of the unsaturated alcohols should be further studied as potential antiviral agents, particularly for application to herpesvirus-infected areas of the skin and accessible epithelium.
Induction of Streptomycin Uptake in Resistant Strains of
Escherichia coli
Authors: Höltje Joachim-Volker
Published: June 2012

Different streptomycin-resistant strains of
Escherichia coli
, including an R100 plasmid-carrying strain of
E. coli
W3110, the ribosomally resistant mutant SM10, and the spontaneous revertant from dependence to independence d1023, exhibited poor accumulation capacity for aminoglycoside antibiotics. This was due to a failure of these mutants to induce the general polyamine transport system that is utilized by streptomycin to enter the cell. It is shown that the aminoglycoside kanamycin, which is effective on these streptomycin-resistant strains, was capable of inducing the uptake of streptomycin, thus giving rise to streptomycin accumulation up to wild-type levels. Plasmid-determined resistance, which has been speculated to be the result of a blockage of the uptake system by modified antibiotic molecules, cannot be overcome by the induction of streptomycin transport. Increase in permeability of the antibiotic does not affect the susceptibility of the bacteria. It is shown that all of the antibiotic taken up was enzymatically modified. R-plasmid-conferred resistance to aminoglycosides is therefore explained by the inactivation of the antibiotic entering the bacterial cell.
Treatment of Experimental
Staphylococcus aureus
Abscesses: Comparison of Cefazolin, Cephalothin, Cefoxitin, and Cefamandole
Authors: Kaye Donald , Parsons James N. , Carrizosa Jaime , Kobasa William D.
Published: June 2012

Cefazolin (CZ), cephalothin (CF), cefoxitin (CX), and cefamandole (CM) were evaluated in therapy of
Staphylococcus aureus
infection produced in perforated table tennis balls placed intraperitoneally in rabbits. Four weeks after placement of two balls in each rabbit, a beta-lactamase producing strain of
S. aureus
was injected into one of the balls. Twenty-four hours later therapy was initiated with 40 mg of CZ or 80 mg of CF, CX, or CM per kg intramuscularly every 6 h. After 24 h of treatment, the mean log
10
colony-forming units per ml were 7.1 for CZ, 6.7 for CF, 6.5 for CX, and 7.2 for CM. After 72 h the mean log
10
colony-forming units per ml were 5.0 for CZ, 4.1 for CF, 3.6 for CX, and 5.6 for CM. After 8 days, the titers were 1.6/ml for CZ, 1.0 for CF, 1.9 for CX, and 3.6 for CM. CZ serum levels were about double CF and CX levels and about two-thirds of CM levels. In sterile ball fluid CZ and CM levels were more than double CF or CX concentrations. Concentrations of all four antibiotics were lower in infected balls.
Effect of Cephapirin on Formation of
d
-Alanine Carboxypeptidase in Growing
Bacillus subtilis
Cells
Authors: White John S. , Astill Mark , Lawrence Paul J.
Published: June 2012

Cephapirin was utilized to examine the interaction of β-lactam antibiotics with growing
Bacillus subtilis
cells and the biological effects simultaneously produced. Saturation binding and quantitative cell death were observed at the cephapirin concentration of 0.1 μg/ml. Cephapirin bound to all penicillin-binding proteins except the
d
-alanine carboxypeptidase. A specific [
14
C]benzylpenicillin-binding assay was developed for the
d
-alanine carboxypeptidase. At the lowest saturating concentration of antibiotic (0.1 μg/ml), cephapirin inhibited formation of the
d
-alanine carboxypeptidase. Upon incubation with cephapirin, 18% of the membranous
d
-alanine carboxypeptidase was released into the media. The data suggest that β-lactam antibiotics may affect the formation of bacterial cytoplasmic membranes in addition to their effect on cell wall synthesis.
Inhibition of
Escherichia coli
K-12 by β-Lactam Antibiotics With Poor Antibacterial Activity: Interaction of Permeability And Intrinsic Activity Against Penicillin-Binding Proteins
Authors: Curtis Nigel A. C. , Brown Carol , Boxall Mike , Boulton Michael G.
Published: June 2012

The effect of methicillin, cloxacillin, 1078/1/1, penicillin G, and cephaloridine upon the penicillin-binding proteins of a permeability mutant of
Escherichia coli
K-12 and its isogenic wild type have been investigated. Comparison of the 50% inhibition values for the antibiotics against the penicillin-binding proteins of the two strains with the minimal inhibitory concentrations for the same compounds indicates that methicillin, cloxacillin, 1078/1/1, and to a lesser extent penicillin G, owe their poor antibacterial activity to exclusion from the bacterial cell, whereas cephaloridine is not excluded and is equally active against both the mutant and its wild type. The results further suggest that the lesion in the permeability mutant
E. coli
DC2 allows free access of all the compounds tested to the inner membrane target proteins.
In Vitro Activity of Piperacillin Compared with That of Carbenicillin, Ticarcillin, Ampicillin, Cephalothin, and Cefamandole Against
Pseudomonas aeruginosa
and
Enterobacteriaceae
Authors: Shah Pramod P. , Briedis Dalius J. , Robson Hugh G. , Conterato James P.
Published: June 2012

Piperacillin (T-1220), a semisynthetic derivative of aminobenzylpenicillin, was more active than either carbenicillin or ticarcillin against
Pseudomonas aeruginosa
; over 60% of isolates were inhibited at a concentration of 6.3 μg/ml. Piperacillin was bactericidal for 84% of
Pseudomonas
strains at 100 μg/ml, carbenicillin killed 60%, and ticarcillin killed 68% at that concentration. Piperacillin was also more active than the other penicillins against isolates of
Escherichia coli, Enterobacter
, and
Proteus mirabilis
. The combination of piperacillin and tobramycin, demonstrating synergistic inhibition of 87% of strains of
P. aeruginosa
, was the most active of the penicillin-aminoglycoside combinations tested for synergism.
Comparative Study of Anti-Pseudomonas Activity of Azlocillin, Mezlocillin, and Ticarcillin
Authors: Coppens L. , Klastersky J.
Published: June 2012

The anti-pseudomonas activities of azlocillin and mezlocillin were compared with that of ticarcillin. We measured the minimal inhibitory and minimal bactericidal concentrations of the three drugs against 20 different strains of
Pseudomonas aeruginosa
and found significantly lower values for azlocillin than for the other two drugs. We then infused 5 g of each drug into 10 volunteers on three consecutive days and determined the serum levels of the three antibiotics at 1-h intervals from 1 to 6 h after injection. The levels of azlocillin were significantly higher than those of mezlocillin and ticarcillin (at 1 h: 236.55 μg/ml ± 12.9 for azlocillin, 192.45 μg/ml ± 28.8 for mezlocillin, and 131.5 μg/ml ± 10.9 for ticarcillin). The inhibitory and bactericidal activities of the sera obtained 1 and 6 h after the injection against the same 20 strains of
P. aeruginosa
demonstrated a significantly greater anti-pseudomonas activity of azlocillin when compared with mezlocillin and ticarcillin; mezlocillin and ticarcillin had approximately the same activity. The mean values for bactericidal activity against the strains tested were 1/32 for azlocillin, 1/8 for mezlocillin, and 1/8 for ticarcillin. Azlocillin thus appears to be a promising anti-pseudomonas drug and should be tested in clinical trials.
In Vitro Evaluation of Seven Cationic Detergents as Antiplaque Agents
Authors: Tanzer J. M. , Slee A. M. , Kamay B. , Scheer E. R.
Published: June 2012

The bactericidal efficacy of seven cationic detergents was studied in vitro against intact performed plaques of representative strains of four oral dental plaque-forming microorganisms:
Streptococcus mutans, Streptococcus sanguis, Actinomyces viscosus
, and
Actinomyces naeslundii
. Both absolute (plaque bactericidal index) and relative (chlorhexidine coefficient) indexes of antiplaque activity were established. Only cetyltrimethylammonium bromide was more efficacious than the reference agent, the bisbiguanide chlorhexidine, for the apparently more potent tooth-adherent cariogenic and periodontopathic elements, respectively, of the in vivo plaque microflora,
S. mutans
and
A. viscosus
.
In Vitro Activity of HR 756, a New Cephalosporin, Against
Neisseria gonorrhoeae
Authors: Murray Patrick R. , Christman Judy L. , Medoff Gerald
Published: June 2012

The in vitro activity of HR 756 was compared with penicillin, cefamandole, cefoxitin, and tetracycline against
Neisseria gonorrhoeae
. A total of 192 randomly selected isolates (of which 23 had minimal inhibitory concentrations of ≥0.5 μg/ml for penicillin) and three β-lactamase-producing isolates were tested. HR 756 was the most active antibiotic tested, with more than 90% of the isolates inhibited by 0.008 μg/ml and all inhibited by 0.25 μg/ml.
In Vitro Activity of Mezlocillin and Its Related Compounds Against Aerobic and Anaerobic Bacteria
Authors: Thadepalli Haragopal , Roy Ira , Bach Vinh T. , Webb David
Published: June 2012

A total of 900 clinical isolates of aerobic (462 isolates) and anaerobic (438 isolates) bacteria were tested against mezlocillin in comparison with other penicillins, and the aerobes were also tested against cephalothin, cefoxitin, and cefamandole. Among penicillins, mezlocillin was the most effective against
Escherichia coli, Klebsiella pneumoniae, Salmonella
species,
Pseudomonas aeruginosa
, and
Bacteroides fragilis
. Mezlocillin was more effective than cephalothin against
Klebsiella pneumoniae
.
Sporulation and the Production of Serine Protease and Cephamycin C by
Streptomyces lactamdurans
Authors: Ginther Charles L.
Published: June 2012

Streptomyces lactamdurans
, producer of the antibiotic cephamycin C, excretes at least two proteases. Physiological studies indicate that antibiotic synthesis and serine protease formation are coordinately regulated. Both are produced only after culture growth ends, and they appear with essentially identical kinetics. In addition, strains which produce superior levels of cephamycin C form equally superior levels of the serine protease. Genetic evidence reveals that the syntheses of the antibiotic and serine proteases are associated with sporulation. Mutants which fail to produce aerial hyphae (bald mutants) also fail to synthesize the antibiotic and serine proteases.
Comparative In Vitro Activity of Azlocillin, Ampicillin, Mezlocillin, Piperacillin, and Ticarcillin, Alone and in Combination with an Aminoglycoside
Authors: White G. Wesley , Malow James B. , Zimelis Victoria M. , Pahlavanzadeh Hossein , Panwalker Anand P. , Jackson George Gee
Published: June 2012

The in vitro activities of the newer semisynthetic penicillins azlocillin, mezlocillin, and piperacillin were compared with those of ampicillin and ticarcillin by using 290 clinical laboratory isolates. Piperacillin and mezlocillin were the most active against
Escherichia coli, Proteus mirabilis, Klebsiella
spp., and
Enterobacter
spp. When
Pseudomonas aeruginosa
was tested, piperacillin and azlocillin were more active than either mezlocillin or ticarcillin.
Streptococcus pneumoniae
and
Haemophilus influenzae
species were highly susceptible to all of the penicillins tested. Ticarcillin had relatively poor activity against enterococci. The rate of bacterial killing with multiples of the minimal inhibitory concentration of azlocillin, ampicillin, or ticarcillin was tested for
E. coli, P. mirabilis, P. aeruginosa
, and
Klebsiella
spp. Increasing concentrations increased the bactericidal effect. The effect of combining azlocillin, ampicillin, or ticarcillin with an aminoglycoside was studied by using both killing curves and checkerboards. The isobolograms constructed from the checkerboards showed a synergistic pattern for the organisms tested, which included
E. coli, P. aeruginosa, Klebsiella
spp.,
P. mirabilis
, and enterococci. However, the rate of killing was increased by the combination only for
P. aeruginosa
and enterococci.
Comparative Susceptibility of Penicillinase-Positive and -Negative
Neisseria gonorrhoeae
to 30 Antibiotics
Authors: Hall Wendell H. , Schierl Elizabeth A. , Maccani James E.
Published: June 2012

The minimal inhibitory concentrations of 30 antibiotics were determined by the agar dilution method for 17 penicillinase-positive and 50 penicillinase-negative strains of
Neisseria gonorrhoeae
. The latter included 42 strains that were penicillin susceptible (pen S) (minimal inhibitory concentration, <0.125 μg/ml) and 8 strains with intermediate resistance to penicillin (pen I; minimal inhibitory concentration, 0.125 to 0.5 μg/ml). Two penicillinase-resistant penicillins (methicillin and nafcillin) were inhibitory for penicillin-resistant (pen R) strains. Three new cephalosporins (cefuroxime, cefamandole, cefaclor) and a cephamycin (cefoxitin) were bacteriostatic (minimal inhibitory concentration ≤0.8 μg/ml) for 90% of pen S, pen I, and pen R strains. Pen I strains were more resistant than pen R strains to 6 of 13 cephalosporins. Rifampin, erythromycin, spectinomycin, chloramphenicol, and the tetracyclines were inhibitory for both pen S and pen R strains. The minimal bactericidal concentrations of cefuroxime, cefamandole, cefaclor, and cefoxitin were measured for 17 pen R strains and eight pen I strains by serial dilution of the antibiotics in Trypticase soy broth supplemented with 1% Iso VitaleX and 1% hemoglobin. All tubes were subcultured after overnight incubation at 37°C. Cefuroxime and cefoxitin were bactericidal at low concentrations (minimal bactericidal concentration, ≤1.0 μg/ml) for 16 of 17 pen R strains and 6 of 8 pen I strains.
Effect of Clavulanic Acid on the In Vitro Synergism Between Carbenicillin and Gentamicin Against
Serratia marcescens
Authors: Sirisanthana Thira , Lerner Stephen A.
Published: June 2012

Clavulanic acid, a potent β-lactamase inhibitor, reduced the minimum inhibitory concentrations of carbenicillin for 13 of 15 clinical isolates of
Serratia marcescens
by at least eightfold. The combination of clavulanic acid and carbenicillin also exhibited synergistic activity with gentamicin against 11 of 15 isolates tested, including 9 of 10 strains which were highly resistant to carbenicillin (minimum inhibitory concentration ≥ 8,000 μg/ml) and had previously been found resistant to the synergistic activity between carbenicillin and gentamicin.
Influence of Single or Multiple Doses of Gentamicin and Netilmicin on Their Cortical, Medullary, and Papillary Distribution
Authors: Bergeron Michel G. , Trottier Sylvie
Published: June 2012

In this study, the comparative intrarenal distribution and accumulation of both gentamicin and netilmicin were investigated in normal rats. The animals received 1, 3, or 14 injections of 10 mg of gentamicin or netilmicin per kg. A total of 324 animals and 648 kidneys were analyzed. These animals were sacrificed at from 1 h to 25 days after the intraperitoneal injections. At each timed interval, the serum, urine, cortex, medulla, and papilla were analyzed for antimicrobial content. The peak serum values of gentamicin (8 to 12 μg/ml) and netilmicin (9 to 14 μg/ml) were close to those found in humans. There was a progressive increase in the cortical concentrations of both antibiotics from a low of 53 μg/g to a high of 719 μg/g when the animals were given increasing doses of the agents. At most timed intervals, the concentrations of gentamicin within the cortex were slightly lower than those of netilmicin. The accumulation of the drugs was also demonstrated in the medulla, where therapeutic levels could be detected for up to 25 days after the cessation of therapy. Even though gentamicin and netilmicin were transiently present in the papilla after 1 or 3 injections, both drugs could still be detected in the papilla on day 25 after 14 doses. The urinary concentration closely paralleled the papillary concentration. If applicable to humans, the persistence of high levels of both drugs within the medulla and papilla may have therapeutic implications.
Characteristics of Herpesvirus Mutants Resistant to Phosphonoformate and Phosphonoacetate
Authors: Eriksson Bertil , Öberg Bo
Published: June 2012

Mutants of herpes simplex virus type 1, resistant to phosphonoformate (PFA) and phosphonoacetate (PAA), have been selected in cell culture. The PFA-resistant mutant (HSV-PFA
r
) and the PAA-resistant mutant (HSV-PAA
r
) were also resistant to PAA and PFA, respectively. This cross-resistance indicates that PFA and PAA interact at the same site. The HSV-PFA
r
had a decreased susceptibility to vidarabine, but no difference in sensitivity to idoxuridine (5-iodo-2′-deoxyuridine) was observed when compared to the wild type. The induced deoxyribonucleic acid polymerases isolated from cells infected with HSV-PFA
r
and HSV-PAA
r
were both cross-resistant to inhibition by PFA and PAA. No increased resistance to vidarabine triphosphate could be observed, but the susceptibility to inhibition by pyrophosphate was about two times lower. None of the mutants showed any increased temperature sensitivity
Bactericidal and Bacteriostatic Action of Chloramphenicol Against Meningeal Pathogens
Authors: Rahal James J. , Simberkoff Michael S.
Published: June 2012

The bacteriostatic and bactericidal effects of chloramphenicol, ampicillin, tetracycline, and sulfisoxazole were compared against several potential meningeal pathogens. Chloramphenicol is bactericidal at clinically achievable concentrations against
Haemophilus influenzae, Streptococcus pneumoniae
, and
Neisseria meningitidis
. It is bacteriostatic against gram-negative bacilli of the family
Enterobacteriaceae
and against
Staphylococcus aureus
. Chloramphenicol has proven highly efficacious in the treatment of bacterial meningitis caused by those organisms against which it is bactericidal at low concentrations. Because leukocytic phagocytosis in the subarachnoid space is inefficient, we propose that bactericidal activity in cerebrospinal fluid is important for optimal therapy of bacterial meningitis. Chloramphenicol does not provide such activity in meningitis caused by enteric gram-negative bacilli.
Isolation and Properties of Metronidazole-Resistant Mutants of
Bacteroides fragilis
Authors: Britz M. L. , Wilkinson R. G.
Published: June 2012

Metronidazole-resistant mutants of
Bacteroides fragilis
, isolated after mutagenesis, had diminished ability to take up and metabolize the drug. All the metronidazole-resistant strains had depressed levels of pyruvate dehydrogenase compared with parent cultures. Their end products of glucose metabolism also differed from normal
B. fragilis
products and were consistent with deficiencies in pyruvate dehydrogenase activity.