bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro activity of N-formimidoyl thienamycin (MK0787) against resistant strains of Pseudomonas aeruginosa, Staphylococcus epidermidis, Serratia marcescens, and Enterococcus spp
Authors: Livingston W K , Elliott A M , Cobbs C G
Published: June 2012

The in vitro activities of N-formimidoyl thienamycin (MK0787) and nine other antibiotics were tested against 129 clinical isolates, including 71 of enterococci, 34 of Staphylococcus epidermidis, 17 of Pseudomonas aeruginosa, and 7 of Serratia marcescens. These isolates exhibited a variety of resistant patterns: 97% of the enterococci were resistant to moxalactam; 71 and 81% of the S. epidermidis isolates were resistant to methicillin and penicillin, respectively; 47, 53, and 53% of the P. aeruginosa isolates were resistant to carbenicillin, cefotaxime, and moxalactam, respectively; and all S. marcescens isolates were resistant to amikacin, gentamicin, and tobramycin. With respect to concentrations required to inhibit growth of 90% of the isolates, N-formimidoyl thienamycin was more active than any compound tested. Determination of the concentration required to inhibit growth of 50% of the isolates showed N-formimidoyl thienamycin to be more active than any other agent against S. epidermidis, S. marcescens, and enterococci, but against Pseudomonas isolates it was less active than amikacin, gentamicin, and tobramycin. This preparation is potentially useful for patients with serious infection caused by resistant bacteria; enterococcal and S. epidermidis endocarditis infections may be special situations which merit clinical trials.
Amikacin and gentamicin accumulation pharmacokinetics and nephrotoxicity in critically ill patients
Authors: French M A , Cerra F B , Plaut M E , Schentag J J
Published: June 2012

Twenty-five critically ill adults receiving blood level-adjusted doses of amikacin were prospectively studied with serum, urine, and, when possible, tissue amikacin concentrations. These data were fitted to a two-compartment pharmacokinetic model. Prolonged urine collections or postmortem tissues (or both) were used to confirm predicted tissue accumulation. Nephrotoxicity was also investigated. Patients were defined as having renal damage if they showed an increase in serum creatinine of greater than 0.5 mg/100 ml, an increase in urine beta 2-microglobulin of greater than 50 mg/day, and presence of urinary casts of greater than 500/ml. Renal damage was attributed to amikacin if there was, in addition to the above, tissue accumulation of amikacin of greater than 600 mg. These patients were matched with 25 patients treated with gentamicin during the same time period. There were no statistical differences between the gentamicin- and amikacin-treated patients in age, sex, weight, base-line creatinine clearance, concurrent cephalosporins or diuretics, treatment duration, site of infection, normalized (amikacin/gentamicin dosing ratio of 3:1) total dose, mortality, or tissue accumulation. More amikacin-treated patients (19 of 25) than gentamicin-treated patients (9 of 25) received prior aminoglycosides (P less than 0.01). The only pharmacokinetic parameter that differed between amikacin and gentamicin was a greater K21 for gentamicin. Nephrotoxicity was observed in 4 gentamicin was a greater K21 for gentamicin. Nephrotoxicity was observed in 4 gentamicin-treated patients (16%) and 5 amikacin-treated patients (20%). At a 3:1 dosing ratio, there were no significant differences between amikacin and gentamicin two-compartment pharmacokinetics and nephrotoxic potential in matched critically ill patients, but the trend of these data showed greater amikacin tissue accumulation. However, at an amikacin/gentamicin dosing ratio of 4:1, their tissue accumulation potential appeared to be almost identical.
Mutational loss of susceptibility to mutacin GS-5 in Streptococcus pyogenes: surface protein in a tolerant variant
Authors: Franker C K
Published: June 2012

A variant (S4340) nonsusceptible to mutacin GS-5 was previously obtained from a strain of Streptococcus pyogenes susceptible to this bacteriocin. The variant was found to adsorb as much bacteriocin as parent cells and exhibit similar susceptibility to seven antibiotics and two detergents. Electrophoretic analysis of protein dissociated from mutant cells by brief sonication revealed the presence of a 74,000-dalton polypeptide not discernible in profiles obtained from susceptible parent cells. The precise role of this tolerance-associated marker remains to be determined. The protein does not appear to be an exported product transiently associated with the cell envelope.
Short-course human leukocyte interferon in treatment of herpes zoster in patients with cancer
Authors: Merigan T C , Gallagher J G , Pollard R B , Arvin A M
Published: June 2012

Because of encouraging results when human leukocyte interferon was given for 5 to 7 days to treat early localized herpes zoster in patients with cancer, a small placebo-controlled, randomized, double-blind trial was set up involving only 48 h of therapy. In this trial, there was no effect on acute pain or disease progression in the primary dermatome. However, a modest but significant effect was noted in that distal cutaneous spread was diminished in the treated patients compared with the controls and the treated patients had diminished severity and duration of postherpetic neuralgia. No evidence of impairment in varicella-zoster-specific lymphocyte transformation was observed in interferon-treated patients.
Inhibition of hepatitis B virus deoxyribonucleic acid polymerase by the 5'-triphosphates of 9-beta-D-arabinofuranosyladenine and 1-beta-D-arabinofuranosylcytosine
Authors: Hess G , Arnold W , Meyer zum Büschenfelde K H
Published: June 2012

9-beta-D-Arabinofuranosyladenine (ara-A), 1-beta-D-arabinofuranosylcytosine (ara-C), and their 5'-triphosphates (ara-ATP and ara-CTP) were tested for ability to inhibit the hepatitis B virus (HBV)-associated deoxyribonucleic acid (DNA) polymerase. Ara-C did not inhibit the HBV DNA polymerase at the concentrations tested, ara-A did so by 50% at a concentration of 30 mM, with the inhibition noncompetitive with respect to deoxyadenosine 5-triphosphate (dATP). Ara-ATP and ara-CTP inhibited the DNA polymerase test competitively with respect to dATP and dCTP, respectively. Both compounds were also active after initiation of the DNA polymerase reaction. The inhibition caused by ara-ATP and ara-CTP was shown to be reversible, with no evidence that ara-ATP or ara-CTP was incorporated into the HBV DNA.
Susceptibility of anaerobic bacteria to nine antimicrobial agents and demonstration of decreased susceptibility of Clostridium perfringens to penicillin
Authors: Marrie T J , Haldane E V , Swantee C A , Kerr E A
Published: June 2012

The activity of moxalactam, cefoxitin, cephalothin, cefamandole, chloramphenicol, clindamycin, metronidazole, and ticarcillin was determined against 344 isolates of anaerobic bacteria. The activity of penicillin G was determined as well for 234 isolates not of the Bacteroides fragilis group. Moxalactam was more active than cephalothin and cefamandole and slightly less active than cefoxitin. Metronidazole was the most active antimicrobial agent against the B. fragilis group, whereas chloramphenicol was most active overall. Clostridium species were the most resistant group of organisms tested. Relatively high concentrations of penicillin were required to inhibit the C. perfringens strains: 80% at 0.5 U/ml and 100% at 16 U/ml. Our study demonstrates the need for periodic anaerobe susceptibility testing in order to better guide empiric antibiotic therapy.
Activity of a new cephalosporin antibiotic, Ro 13-9904 against dense populations of selected enterobacteria
Authors: Greenwood D , Eley A
Published: June 2012

Ro 13-9904 is a new cephalosporin antibiotic with a wide spectrum of activity similar to that of cefotaxime and some other newer beta-lactam compounds. In the present study, the response to Ro 13-9904 of 13 strains of enterobacteria, selected on the basis of differential patterns of susceptibility to beta-lactam agents, was investigated. The new cephalosporin displayed high intrinsic activity against most of the enterobacteria tested, but a group of Klebsiella and Hafnia alvei strains was identified against which Ro 13-9904 (and cefotaxime) exhibited reduced activity. Investigation of these strains revealed several different types of response to Ro 13-9904 and cefotaxime. Although such "difficult" strains represent a small minority of clinical isolates, it is likely that it is this group of strains against which the new generation of highly potent, broad-spectrum beta-lactam antibiotics will display significant differential activity.
In vitro activity of Ro 13-9904, a new beta-lactamase-stable cephalosporin
Authors: Verbist L , Verhaegen J
Published: June 2012

The minimal inhibitory concentration (MIC) of Ro 13-9904 against 245 clinical isolates was determined by an agar dilution method. The activity of Ro 13-9904 against most Enterobacteriaceae was similar to that of cefotaxime; it was slightly more active than cefotaxime against Proteus mirabilis, Providencia species, and Serratia marcescens, but slightly less active against Klebsiella species. Ro 13-9904 was twofold more active than cefotaxime and threefold more active than ticarcillin against ticarcillin-susceptible Pseudomonas aeruginosa, with a mean MIC of 7.2 micrograms/ml; isolates highly resistant to ticarcillin were inhibited by a mean MIC of 17.2 micrograms/ml. Ro 13-9904 was fourfold more active than ampicillin against susceptible Haemophilus influenzae and was equally active against beta-lactamase-producing isolates. Ro 13-9904 was highly active against pneumococci and moderately active (MIC, 4 micrograms/ml) against Staphylococcus aureus isolates, whether they were susceptible or resistant to penicillin G. Oxacillin-resistant S. aureus and Streptococcus faecalis were completely resistant to Ro 13-9904 (MIC, greater than 128 micrograms/ml).
Preferential inhibition of ribonucleic acid synthesis by a new thiosemicarbazone possessing antibacterial and antiparasitic properties
Authors: Brown R E , Stancato F A , Wolfe A D
Published: June 2012

We determined the influence of the azacycloheptane derivative (H) of a 2-acetylpyridine thiosemicarbazone on growth and macromolecular synthesis in Escherichia coli AT-9. Thiosemicarbazone H caused bacteriostasis and a primary inhibition of ribonucleic acid synthesis; secondary effects included inhibition of deoxyribonucleic acid and protein synthesis. Addition of cooper or other transition elements was not necessary for these inhibitions.
Macrolide-lincosamide-streptogramin resistance patterns in Clostridium perfringens from animals
Authors: Dutta G N , Devriese L A
Published: June 2012

Different patterns of resistance against commonly used macrolide, lincosamide, and streptogramin antibiotics were found in Clostridium perfringens of animal origin. The patterns were designated as (i) macrolide-lincosamide-streptogramin group B generalized resistance, (ii) macrolide-lincosamide generalized resistance, (iii) macrolide-lincosamide inducible resistance, and (iv) macrolide-lincosamide-streptogramin low-level generalized resistance. The strains of the fourth pattern were able to inactivate pristinamycin and virginiamycin. The macrolide-susceptible strains showed a bimodal distribution of lincomycin and clindamycin susceptibility levels. The susceptible strains were inhibited by 0.25 micrograms of lincomycin per ml and 0.03 micrograms of clindamycin per ml. The low-level resistant strains were inhibited at concentrations of 2 to 4 micrograms of lincomycin per ml and 0.5 to 2 micrograms of clindamycin per ml.
Stimulation of human and canine neutrophil metabolism by amphotericin B
Authors: Supapidhayakul S R , Kizlaitis L R , Andersen B R
Published: June 2012

The effect of an antifungal agent, amphotericin B, on human and canine neutrophil metabolism was studied. Commercial preparations of amphotericin B in concentrations ranging from 5 to 100 micrograms/ml stimulated neutrophil chemiluminescence in the presence of 10(-8) M luminol. This response was blocked by 2-deoxyglucose, a metabolic inhibitor, and by the absence of extracellular calcium ions. Neither pure amphotericin B nor the solubilizing agent present in the commercial preparation, alone or in combination, stimulated neutrophil chemiluminescence. Commercial amphotericin B caused an increase in oxygen uptake by neutrophils but no detectable superoxide anion production. Neutrophils were injured by commercial amphotericin B, as shown by an increase in trypan blue dye uptake but not cell lysis. Binding of amphotericin B to neutrophil membrane sterol with a subsequent alteration in membrane configuration is the most likely cause of metabolic stimulation.
Peritoneal fluid concentrations of gentamicin in patients with spontaneous bacterial peritonitis
Authors: Richey G D , Schleupner C J
Published: June 2012

Simultaneous peritoneal fluid and serum gentamicin assays were performed at 1- or 4-h intervals after the intravenous administration of gentamicin (3 to 5 mg/kg per day) during nine episodes of spontaneous bacterial peritonitis in cirrhotic patients. Mean peritoneal fluid levels were 4.2 micrograms/ml, whereas simultaneous mean serum levels were 6.1 micrograms/ml (mean percent diffusion into ascites of 67.8%). Three additional patients with uninflamed ascites demonstrated lower levels of diffusion. Regression analysis revealed a positive correlation between simultaneous serum and peritoneal fluid levels. We conclude that diffusion of gentamicin from serum into peritoneal fluid during spontaneous peritonitis is therapeutically adequate if sufficient serum levels are maintained.
Effect of Carbon Dioxide and pH on Susceptibility of
Bacteroides fragilis
Group to Erythromycin
Authors: Hansen Sharon L. , Swomley Patricia , Drusano George
Published: June 2012

We examined the effects of pH and incubation in a CO
2
-containing atmosphere on the activity of erythromycin against 81 strains of the
Bacteroides fragilis
group. A striking reduction in erythromycin activity was noted when the pH decreased below 7.0 and when the organisms were incubated with CO
2
.
Primaquine: metabolism by microorganisms and 13C nuclear magnetic resonance assignments
Authors: Clark A M , Huford C D , McChesney J D
Published: June 2012

Primaquine (I), a 6-methoxy-8-aminoquinoline derivatives used for the treatment of malaria, has been subjected to metabolic studies using microorganisms. A total of 77 microorganisms (fungi and Streptomyces spp.) were evaluated for their ability to metabolize primaquine. Of these, 23 were found to convert primaquine to one or more metabolites (thin-layer chromatography analysis). Preparative scale fermentation of primaquine with four different microorganisms resulted in the isolation of two metabolites, identified as 8-(4-acetamido-1-methylbutylamino)-6-methoxyquinoline (II) and 8-(3-carboxyl-1-methylpropylamino)-6-methoxyquinoline (III). The structures of the metabolites were proposed based primarily on a comparison of the 13C nuclear magnetic resonance spectra of II and the methyl ester of III (IV) with that of primaquine. The structures of both metabolites II and III were confirmed by direct comparison with authentic samples.
Mode of action of Myxococcus xanthus antibiotic TA
Authors: Zafriri D , Rosenberg E , Mirelman D
Published: June 2012

Antibiotic TA inhibited incorporation of diaminopimelic acid and uridine diphosphate-N-acetylglucosamine into Escherichia coli cell walls without altering the ratio of cross-linked to uncross-linked peptidoglycan. Formation of the lipid intermediate was not blocked by TA, suggesting that TA interferes with polymerization of the lipid-disaccharide-pentapeptide.
Effect of ribavirin on Rous sarcoma virus transformation
Authors: Jenkins F J , Chen Y C
Published: June 2012

Ribavirin inhibited the expression of cellular transformation in normal rat kidney cells transformed by a temperature-sensitive mutant of rous sarcoma virus and chicken embryo fibroblasts infected with either a temperature-sensitive mutant or wild-type Rous sarcoma virus. Ribavirin also inhibited replication of the Rous sarcoma viruses in chicken embryo fibroblasts. The effect of ribavirin on cellular transformation was not permanent, as removal of the drug resulted in reversion to the transformed phenotype. The concentration of ribavirin necessary to inhibit the expression of cellular transformation was cytostatic for the cell lines used in this study.
Molecular nature of a streptomycin and sulfonamide resistance plasmid (pBP1) prevalent in clinical Escherichia coli strains and integration of an ampicillin resistance transposon (TnA)
Authors: van Treeck U , Schmidt F , Wiedemann B
Published: June 2012

A small, nonconjugative plasmid, designated pBP1, was originally found in different fecal Escherichia coli serotypes isolated from a healthy proband. Of a total number of 130 hospital strains of E. coli subsequently studied, 8.5% yielded plasmid of the pBP1 type. This R plasmid specifies resistance to streptomycin (Sm) and sulfonamides (Su) and has a mass of 4.0 megadaltons. Inactivation of streptomycin is due to the aminoglycoside phosphotransferase APH-(3 "). A physical map was constructed by analysis with restriction endonucleases. Another small plasmid, pBP1-1, was isolated from one of the hospital strains and characterized as an enlarged pBP1 replicon containing an additional deoxyribonucleic acid sequence identified as a transposable element for ampicillin resistance (TnA). Plasmid pBP1-1 was cleaved by restriction enzymes for identification of the transposon sequence which codes for a TEM 1 beta-lactamase. The sequence organizations in the Sm Su plasmids RSF1010 and pBP1 were shown to be identical for regions specifying streptomycin and sulfonamide resistance, but different for the region containing the origin of replication and genes for replicative functions. Thus, RSF1010, which has been considered as the prototype of Sm Su plasmids, and pBP1, which is at least as frequent in clinical isolates as RSF1010, do not have a single common ancestor.
Antibacterial activity of 2',3'-dideoxyadenosine in vivo and in vitro
Authors: Beskid G , Eskin B , Cleeland R , Siebelist J , Cappetta A , Hill A D , Geiger R H
Published: June 2012

2',3'-Dideoxyadenosine (DDA) was shown not only to possess antibacterial activity in vitro against a variety of Enterobacteriaceae, but also to be effective in vivo, DDA was active in experimental mouse infections by the oral route against 5 Salmonella strains, 2 of 3 Arizona strains, 5 of 7 Citrobacter strains, 3 of 8 Klebsiella strains, 3 of 5 Escherichia strains, 1 of 3 Shigella strains, and 3 of 15 Serratia strains at concentrations generally well below the toxic level. Closely related compounds, with the exception of 2',3'-dideoxyinosine, were found to be inactive in vivo, indicating that a high degree of structural specificity was required for activity. The synthesis of deoxyribonucleic acid was inhibited by DDA in those strains susceptible in vitro to DDA, whereas ribonucleic acid and protein syntheses were not affected. The concentration of DDA which inhibited bacterial deoxyribonucleic acid synthesis by 50% was calculated based on the relative rates of deoxyribonucleic acid synthesis in ;the absence and in the presence of DDA. This value correlated well with the minimal inhibitory concentration determined by the in vitro broth dilution assay but not always with in vivo activity determined by the mouse protection test.
Trimethoprim-rifampin, a new combination agent: efficacy in localized urinary infection and influence on microflora
Authors: Bourgault A M , Forward K R , Ronald A R , Harding G K , Thomson M , Grey G
Published: June 2012

Twenty women with recurrent or persistent urinary tract infections were treated with a fixed combination of trimethoprim-rifampin (TMP-RAM). The site of infection was established by the antibody-coated bacteria test. Sixteen women had upper tract infections (antibody-coated bacteria tests positive); eight were cured, three failed, and five relapsed. All four women with lower tract infections (antibody-coated bacteria tests negative) were cured. Three of five patients with structural abnormalities failed. The 12 cures and 5 relapses were associated with organisms susceptible to either TMP (minimal inhibitory concentration, less than or = to 7 micrograms/ml) or RAM (minimal inhibitory concentration, less than or = to 32 micrograms/ml). In contrast, two of the three failures were associated with organisms resistant to both TMP and RAM. In one patient, RAM resistance emerged during treatment. During therapy, urinary strains were eradicated from the periurethral and anal-canal areas in all but 3 fo 16 patients. Adverse reactions, noted in 16 women, included nausea (10), dizziness (6), headaches (2), rash (1), an blurred vision (1). Antimicrobial susceptibility data on 246 isolated from urinary, periurethral, and anal-canal specimens are included. Our findings suggest that TMP-RAM is effective in urinary infections and may prevent the emergence of RAM-resistant strains.
Rapid radiometric method for determining drug susceptibility of Mycobacterium avium-intracellulare
Authors: Yangco B G , Eikman E A , Solomon D A , Deresinski S C , Madden J A
Published: June 2012

A rapid radiometric method for susceptibility testing of Mycobacterium avium-intracellulare to eight chemotherapeutic agents was compared with a conventional method. Results were available within 72 h by radiometric testing in contrast to 21 days by the conventional method. The radiometric and conventional methods agreed to 61% of the tests, but growth inhibition of greater than or equal to 50% was detectable only by radiometric testing in an additional 36.5% of the tests. In only 2.5% of the tests was the radiometric method unable to detect complete inhibition shown by the conventional method. Quantifiable increases in inhibition with increasing concentration of isoniazid were more frequently detectable by the radiometric method than by conventional testing. The radiometric method is a simple, rapid, and quantitative test for drug susceptibility of mycobacteria and warrants further investigation.
Comparative efficacy and safety of nalidixic acid versus trimethoprim/sulfamethoxazole in treatment of acute urinary tract infections in college-age women
Authors: Iravani A , Richard G A , Baer H , Fennell R
Published: June 2012

One hundred and thirty-five college-age women with acute urinary tract infections caused by gram-negative Enterobacteriaceae were treated by random allocation with either nalidixic acid (NA), 1 g every 6 h for 7 days, or trimethoprim/sulfamethoxazole (TMP/SMZ), 160/800 mg every 12 h for 10 days. The clinical and bacteriological cure rates were 98.0% in each group on the last day of therapy. At 1 and 4 week posttherapy, both the clinical and bacteriological cure rates for NA declined to 90.0 and 74.0% respectively; for TMP/SMZ, they declined to 93.0 and 72.0% respectively. By 4 weeks posttherapy, 96.0% of the TMP/SMZ group and 93.0% of the NA group had remained free of the initial urinary pathogens. Neither drug was associated with emergence of resistant bacterial mutants in urine. The antibody-coated bacteria tested (ACBT) localized 31.5% of the infections of the kidney and 67.7% to the bladder. Upper tract symptoms did not correlate with the presence of a positive ACBT. The response to therapy was similar for the two regimens regardless of ACBT results. After treatment, the emergence of resistant Enterobacteriaceae in fecal flora was 1.1% in the NA group and 2.3% in the TMP/SMZ group. The incidences of drug reactions were 7.0% with NA and 6.3% and TMP/SMZ.
Pharmacokinetics of gentamicin in patients undergoing continuous ambulatory peritoneal dialysis
Authors: Pancorbo S , Comty C
Published: June 2012

Teh pharmacokinetics of gentamicin were studied in seven chronic renal failure patients undergoing continuous ambulatory peritoneal dialysis. Patients received 100 mg of gentamicin in 2 liters of dialysate during an initial pass, and serum and dialysate samples were collected for gentamicin determination. Approximately 49% of the amount introduced into the peritoneal cavity was absorbed systemically during a 6-h cycle. Subsequent clearance of gentamicin from the serum occurred slowly with an elimination half-life of 36 h. Dialysis clearance of gentamicin during continuous ambulatory peritoneal dialysis was 2.94 ml/min.
Comparative tissue distribution of ceforanide, cefazolin, and cefamandole in rats
Authors: Lee F H , Smyth R D , Van Harken D R
Published: June 2012

The comparative tissue distribution of ceforanide, cefazolin, and cefamandole was determined in rats after subcutaneous doses of 100 mg/kg. Ceforanide had the longest plasma half-life, 0.9 h, versus 0.5 h for cefazolin and 0.4 h for cefamandole, and the highest area under the plasma concentration time curve, 324 micrograms x h per ml, versus 184 micrograms x h per ml for cefazolin and 42 micrograms x h per ml for cefamandole. The peak plasma concentrations of ceforanide and cefazolin were 173 and 140 micrograms/ml, respectively, and were threefold higher than that of cefamandole (49 micrograms/ml). Measureable concentrations of the three compounds were found in the liver, kidneys, lungs, submaxillary glands, cervical lymph nodes, bones, heart, abdominal muscles, eyes, and testes, with cefamandole levels being generally lower and more variable. The peak tissue levels of ceforanide and cefazolin were comparable, within the limit of data variation, and were considerably higher than that of cefamandole. The tissue half-lives of these cephalosporins were similar to the respective plasma half-lives.
In Vitro Induction of Resistance to Erythromycin by Its Metabolite
Authors: Majer Jaroslav
Published: June 2012

Of the metabolites isolated from urine samples of patients treated with erythromycin, the 8,9-anhydroerythromycin A 6,9-hemiketal induced in vitro resistance to the parent drug and to carbomycin in the test strain
Staphylococcus aureus
RN 1389.
Nogalamycin inhibits ribonucleic acid synthesis in growing and developing cells of the slime mold Dictyostelium discoideum
Authors: Ennis H L
Published: June 2012

Nogalamycin, an anthracycline antibiotic that intercalates into deoxyribonucleic acid, is a potent inhibitor of ribonucleic acid (RNA) synthesis in the slime mold Dictyostelium discoideum. The antibiotic inhibits RNA synthesis in growing cells and in inactivated spores, and in this way inhibits spore germination. Protein synthesis is much less inhibited. Nogalamycin inhibits ribosomal RNA, transfer RNA, and messenger RNA equally. Polysomes break down in the presence of the drug with a half-life of 220 min, and messenger RNA decays with a half-life of 290 min. The data show that nogalamycin can be employed to inhibit messenger RNA synthesis and is useful in determining messenger RNA decay rates in the slime mold.
Combined Antiviral Effect of Interferon and Acyclovir on Herpes Simplex Virus Types 1 and 2
Authors: Stanwick Trevor L. , Schinazi Raymond F. , Campbell Donald E. , Nahmias Andre J.
Published: June 2012

Acyclovir and human interferon displayed an additive to synergistic effect in reducing the number of herpes simplex viral plaque-forming units in Vero cells, suggesting a therapeutic potential for such combination therapy.
Antiviral Activity of 2-Acetylpyridine Thiosemicarbazones Against Herpes Simplex Virus
Authors: Shipman Charles , Smith Sandra H. , Drach John C. , Klayman Daniel L.
Published: June 2012

2-Acetylpyridine thiosemicarbazone derivatives inhibited the replication of herpes simplex virus types 1 and 2 to a greater extent than cellular deoxyribonucleic acid or protein synthesis.
Synergism, killing kinetics, and antimicrobial susceptibility of group A and B streptococci
Authors: Baker C N , Thornsberry C , Facklam R R
Published: June 2012

The susceptibility of 110 group A and 179 group B streptococci to 25 antimicrobics was tested by broth microdilution and agar disk diffusion tests. Representative strains were used in killing kinetics, penicillin-gentamicin synergy, and minimal bactericidal concentration tests. Group A streptococci were more susceptible than group B streptococci to 17 of the 25 antimicrobics tested. Group A and B streptococci were killed at the same rate if the amount of penicillin used was equivalent to their respective penicillin minimal inhibitory concentrations. Synergism was demonstrated for both group A and B streptococci when penicillin was used at concentrations equal to each respective minimal inhibitory concentration and subinhibitory concentration of gentamicin. This synergy could be demonstrated best using minimal bactericidal concentrations obtained by culturing 3- and 6-h cultures from the microdilution checkerboard tests rather than from 24-h subcultures. A greater synergistic effect was achieved by adding penicillin first and then adding gentamicin rather than in the reverse order, or simultaneously.
Intrarenal concentrations of ampicillin in acute pyelonephritis
Authors: Trottier S , Bergeron M G
Published: June 2012

The intracortical, medullary, and papillary distribution of ampicillin was studied in normal and pyelonephritic rats. At 4 days after induction of pyelonephritis, the animals were given a single injection of 100 mg of ampicillin per kg or were treated for 1 week with two daily doses of 100 mg/kg. Major differences in the intrarenal distribution of ampicillin were noted between normal and pyelonephritic animals. At 2 hours after injection, the concentrations of ampicillin in all parts of the infected kidneys were significantly lower (P less than 0.05) than in normal kidneys. The area under the curve (micrograms.minute per milliliter) over a 4-h period after single injection was much lower in the medulla (6.3 +/- 0.9) and papilla (29.6 +/- 4.2) of infected kidneys than in the medulla (11.2 +/- 1.6) and papilla (44 +/- 10.1) of noninfected kidneys. Whereas the ratio of concentration in tissue to concentration in serum ranged to 11.1 in the papilla of normal animals, this ratio was reduced to 2.4 in the presence of pyelonephritis. The diminution of the concentration gradient was also striking in the urine, where there was a reduction of more than threefold in pyelonephritic animals. One week of therapy resulted in a noticeable reduction of the inflammatory process associated with a return to near-normal intrarenal distribution of ampicillin. In normal rats treated with multiple doses, there were decreases of the antibiotic concentrations in serum and kidneys and in the area under the curve for these tissues.
Susceptibility of enterococci and Listeria monocytogenes to N-Formimidoyl thienamycin alone and in combination with an aminoglycoside
Authors: Eliopoulos G M , Moellering R C
Published: June 2012

The susceptibilities of 12 strains of enterococci and 10 stains of Listeria monocytogenes to N-formimidoyl thienamycin were determined by a standard broth dilution method. Minimal inhibitory concentrations for L. monocytogenes strains were less than 0.25 micrograms/ml. As a group, strains of Streptococcus faecium were less susceptible than Streptococcus faecalis strains, but even for the latter, the minimal inhibitory concentrations were slightly greater than those previously reported. Minimal bactericidal concentrations against all organisms were many-fold higher than the corresponding inhibitory concentrations. In time-kill studies, combinations of N-formimidoyl thienamycin with gentamicin were synergistic against (or they completely sterilized cultures of) all the enterococcal strains and nine to 10 strains of L. monocytogenes. The magnitude of killing by the combinations was comparable to that previously observed with penicillin-gentamicin combinations. N-Formimidoyl thienamycin-tobramycin combinations were synergistic against those strains of S. faecalis and L. monocytogenes tested, but not against those of S. faecium.
Enhanced transmembrane proton conductance in Streptococcus mutans GS-5 due to ionophores and fluoride
Authors: Eisenberg A D , Marquis R E
Published: June 2012

The uptake of protons by intact cells of Streptococcus mutans GS-5 was measured directly by assessing the pH increase in lightly buffered cell suspensions as protons moved across the plasma membrane after acid pulses. The barrier function of the cell membrane for protons was disrupted completely by 5% (vol/vol) butanol. This function was compromised severely by the ionophores valinomycin and gramicidin and by the uncoupler carbonylcyanide-m-chlorophenyl hydrazone. Proton conduction across the membrane was also enhanced by fluoride. It appeared that HF traversed the membrane and acted as a carrier. Once in the relatively alkaline cytoplasm, HF dissociated to yield F- and H+, which acted to acidify the cytoplasm and reduced the pH difference across the membrane.
Methicillin distribution in serum and extravascular fluid and its relevance to normal and damaged heart valves
Authors: Gengo F M , Schentag J J
Published: June 2012

We evaluated the distribution of methicillin into normal and damaged heart valves and the accuracy with which subcutaneous plastic chambers reflected tissue uptake of this antibiotic. A total of 24 male New Zealand rabbits were given constant infusion doses of methicillin through central venous catheters. Five of these animals had their aortic and mitral valves damaged by catheterization of the left ventricle. A total of 19 rabbits had perforated plastic chambers inserted subcutaneously 7 to 10 days before methicillin infusion. In all animals more than 80% of the total infused dose of methicillin was accounted for in the serum, urine, and tissues. In the 12 animals infused to steady state (less than 7 h), the steady-state serum concentrations (11 to 120 micrograms/ml) were equal to the concentrations attained in either peritoneal or tissue chamber fluids. In the 12 animals sacrificed before 7 h, tissue chamber concentrations lagged behind serum and heart tissue concentrations in attaining steady state. Steady-state concentrations in normal heart valves and heart muscles failed to increase proportionally to increased constant infusion doses (8.7 to 87.2 mg/kg per h). The steady-state methicillin concentrations in fibrin-scarred heart valves were invariably higher than the steady-state concentrations in the normal right heart of the same animals (P less than 0.05). Tissue uptake of methicillin was altered in scarred heart valves as compared to normal heart valves, and large-volume subcutaneous tissue chambers misrepresented the uptake rate of methicillin into heart tissues and valves.
Pharmacokinetics of cefamandole in osseous tissue
Authors: Lunke R J , Fitzgerald R H , Washington J A
Published: June 2012

The ability of cefamandole to cross osseous capillary membranes and its concentrations in interstitial fluid spaces are studied in canine cortical bone. Extraction studies were performed by using indicator dilution techniques and demonstrated that cefamandole readily traversed osseous capillary membranes. Volume-of-distribution studies demonstrated that cefamandole was distributed in the plasma and interstitial fluid spaces of cortical bone. There was a direct correlation between the calculated concentrations of cefamandole in the interstitial fluid spaces of bone and the simultaneous serum levels determined by bioassay in animals in which a steady-state equilibrium had been achieved. This suggests that the less expensive and more readily available serum bioassay technique is more useful than bone bioassays in monitoring the osseous concentrations of cefamandole.
Physiological properties of penicillin-binding proteins in group A streptococci
Authors: Gutmann L , Williamson R , Tomasz A
Published: June 2012

We detected five major penicillin-binding proteins (PBPs) in group A streptococci by labeling either cell membrane preparations or live bacteria with tritiated penicillin. All PBPs appeared to be equally accessible to penicillin in vitro and in vivo. Individual PBPs differed in their rates of deacylation, and four of the five PBPs underwent rapid inactivation both in vivo and in vitro. At least two processes seemed to contribute to in vivo inactivation; these were (i) a penicillin-induced release of all five PBPs into the growth medium and (ii) degradation, as evidenced by the appearance of penicillin-labeled protein band of lower molecular weight and also by a gradual increase in material migrating with the same electrophoretic mobility as PBP 3. Inactivation of the PBPs was stimulated greatly by pretreatment of bacteria with gentamicin, cerulenin, or Triton X-100, whereas chloramphenicol, tetracycline, and lincomycin treatments had no such effect.
Nonparallel nephrotoxicity dose-response curves of aminoglycosides
Authors: Hottendorf G H , Barnett D , Gordon L L , Christensen E F , Madissoo H
Published: June 2012

Nephrotoxicity comparisons of aminoglycosides in rats, utilizing large multiples of human doses, have indicated an advantage for netilmicin. However, no nephrotoxicity advantage of netilmicin has been demonstrated at the lower doses used in clinics. Some high-dose studies in rats have also suggested that the slope of the nephrotoxicity dose-response curve of netilmicin was less steep than the slopes of other aminoglycosides. Therefore, the slopes of the nephrotoxicity dose-response curves of gentamicin, amikacin, and netilmicin were compared in 200 rats at low multiples (one to five times) of human clinical doses. Histopathological evaluations of both kidneys from each rat revealed that netilmicin produced equivalent or greater nephrotoxicity as compared with gentamicin and amikacin and that the slope of the nephrotoxicity dose-response curve of netilmicin was approximately one-half as steep as the slopes of amikacin and gentamicin, which were parallel. The distribution of casts excreted in the urine after 2 weeks of dosing and the terminal gross observations corroborated the flatter dose-response slope of netilmicin. Nephrotoxicity advantages predicted by high-dose comparisons with netilmicin in rats are apparently a function of its less steep dose-response slope and therefore may have no relevance to lower doses.
Drug resistance and R plasmids of Escherichia coli strains isolated from pigs, slaughterers, and breeders of pigs in Japan
Authors: Saida K , Ike Y , Mitsuhashi S
Published: June 2012

We isolated 1,120 drug-resistant Escherichia coli strains from pigs, slaughterers, breeders of pigs, and urban residents and examined their drug resistance. With reference to resistance to tetracycline (Tc) chloramphenicol (Cm), streptomycin (Sm), and sulfanilamide (Su), Tcr, Smr, and Sur strains were most frequently isolated from pigs (57.9%), followed by slaughterers (50.2%) and breeders (42.4%). By contrast, the isolation frequencies of Tcr, Smr, and Sur strains from urban residents were low (12.0%). The isolation frequencies of R plasmids from resistant strains were more than 50% in the case of pigs, slaughterers, and breeders, whereas they were only 13.8% in urban residents. Kanamycin-resistant strains were frequently isolated from pigs (40.3%), slaughterers (22.6%), and breeders of pigs (25.4%), but seldom (only 3.4%) from urban residents. With ampicillin resistance, the frequencies of strains from pigs, slaughterers, breeders, and urban residents were 30.0, 21.5, 5.6, and 13.8%, respectively. R plasmids specifying these latter resistances were frequently seen from pigs (24.0%), slaughterers (23.6%), and breeders (21.1%), but they were not isolated from urban residents. The results suggest that the porcine gut can function as a reservoir of antibiotic resistance plasmids which can then be directly transferred to humans, with the highest frequency of such plasmids appearing in people in the most immediate contact with these animals.
Identification of R plasmids mediating gentamicin resistance from Escherichia coli strains in Japan
Authors: Ike Y , Fujisawa-Kon N , Shimizu S , Motohashi K , Hashimoto H , Mitsuhashi S
Published: June 2012

Eight gentamicin-resistant Escherichia coli were identified from among 630 E. coli strans isolated from parenteral infections. All eight strains were multiply resistant and harbored R plasmids mediating gentamicin resistance. The R plasmids specified the formation of two types of aminoglycoside-inactivating enzymes AAD (2") and APH (3').
Enhanced susceptibility of Escherichia coli to intracellular killing by human polymorphonuclear leukocytes after in vitro incubation with chloramphenicol
Authors: Pruul H , Wetherall B L , McDonald P J
Published: June 2012

The effect of brief exposure to chloramphenicol of a pathogenic strain of Escherichia coli on susceptibility to normal human leukocytes was examined. Leukocytes killed chloramphenicol-pretreated E. coli more efficiently than they did untreated controls. Phagocytosis of pretreated bacteria, as measured by the uptake of radiolabeled bacteria and by direct visual count of engulfed bacteria, was not significantly increased. The decrease in viability was associated with enhanced intracellular killing of phagocytosed antibiotic-damaged bacteria. Chloramphenicol pretreatment altered the frequency distribution of intracellular bacteria by decreasing the number of leukocytes containing multiple stainable bacteria. Leukocytes failed to kill chloramphenicol-pretreated E. coli in the presence of phenylbutazone, which allowed an accumulation of intracellular bacteria. These results indicate that exposure of E. coli to chloramphenicol renders the bacteria more susceptible to intracellular killing and degradation.
Pharmacokinetics of moxalactam in subjects with normal and impaired renal function
Authors: Leroy A , Humbert G , Fillastre J P
Published: June 2012

The pharmacokinetics of moxalactam were investigated in five subjects with normal renal function and 21 uremic patients. Normal subjects were given intravenous doses of 7.5 and 15 mg of the drug per kg as bolus injections (1 min) and 30 mg of the drug per kg as a 20-min infusion. Pharmacokinetic data, calculated by using a two-compartment open body model, were similar for the three intravenous doses: the t 1/2 alpha value was within 0.12 to 0.20 h, the t 1/2 beta value was 1.98 to 2.05 h, the central distribution volume (Vc) was 3.81 to 7.04 liters/1.73 m2, and the apparent volume of distribution at steady state (Vdss) was 9.12 to 13.36 liters/1.73 m2, i.e., 13.7 to 20.2% of the body weight. From 82.0 to 97.7% of the dose was recovered, in unchanged form, in urine during 24 h. After a single intramuscular dose of 15 mg/kg in the same subjects with normal renal function, the mean peak serum levels, occurring at 0.95 +/- 0.37 h, were 48.28 +/- 11.81 microgram/ml, the t 1/2 beta value was 2.22 +/- 0.16 h, the renal clearance (CR) was 87.5 +/- 9.4 ml/min per 1.73 m2, and 96.9 +/- 12.7% of the injected dose was found in 24-h urine. Pharmacokinetic data were similar for the two routes of administration. In uremic patients, the t 1/2 beta increased according to the severity of renal failure; it was 4.83 h in patients with creatinine clearances (Ccr) within 30 to 60 ml/min per 1.73 m2, 8.42 h for Ccr values within 10 to 30 ml/min, and 18.95 h in hemodialysis patients. During a 4- to 6-h dialysis session, the t 1/2 beta value was 3.65 h and 51% of the drug was removed by dialysis. The apparent volume of distribution at steady state increased in patients with Ccr values below 10 ml/min; serum and renal clearances decreased in uremic patients, and the nonrenal clearances remained constant in all these patients. From these pharmacokinetic results, linear relationships were found between the kinetic data and the biological parameters of the glomerular filtration rate. Dosage schedules were established, adapted to the degree of renal impairment.
Evaluation of eight cephalosporins in hamster colitis model
Authors: Ebright J R , Fekety R , Silva J , Wilson K H
Published: June 2012

Eight commonly used cephalosporins were evaluated in the hamster colitis mode. They were all found to cause hemorrhagic cecitis and death within 10 days of being given as subcutaneous or oral challenges. Necropsy findings were indistinguishable from clindamycin-induced cecitis. Bacteria-free cecal filtrate obtained from hamsters dying of cephalosporin-induced cecitis contained toxin similar or identical to hat produced by Clostridium difficile isolated from the cecum of a hamster. Daily oral administration of poorly absorbed cephalosporins protected hamsters from clindamycin-induced cecitis and death as long as the cephalosporins were continued. The absorbable cephalosporins were ineffective in protecting hamsters from clindamycin-induced cecitis. This difference probably relates to the lower concentrations of absorbable cephalosporins maintained in the ceca of the hamsters. The possible correlation of these findings to human cases of cephalosporin-induced pseudomembranous colitis is discussed.
Effect of ionized calcium and soluble magnesium on the predictability of the performance of Mueller-Hinton agar susceptibility testing of Pseudomonas aeruginosa with gentamicin
Authors: Casillas E , Kenny M A , Minshew B H , Schoenknecht F D
Published: June 2012

The soluble and ionized calcium and magnesium contents of 18 lots of Mueller-Hinton agar medium from three different manufacturers were analyzed, and the results were correlated with medium performance. A standardized disk diffusion test, with Pseudomonas aeruginosa (ATCC 27853) and a 10-microgram gentamicin disk, served as an indicator of medium performance. Zone diameters correlated well with the ionized calcium values and the sum of the ionized calcium and soluble magnesium values in the different lots (r = -0.88 for both). Zone diameters correlated poorly with ionized magnesium values (r = -0.57), which were best described by a curvilinear relationship. Supplementation of lots of Mueller-Hinton agar medium with equivalent amounts of calcium and magnesium as the chloride, gluconate, or glycerophosphate salts produced identical decreases in zone sizes. Adjustment of deficient lots of Mueller-Hinton agar medium with ionized calcium or soluble magnesium or both (as the gluconate salts), to match the concentrations in lots that provided satisfactory zone sizes (17 to 19 mm), resulted in performance comparable to that of the control lots. Sixteen strains of Pseudomonas aeruginosa, ranging from resistant to susceptible, responded to cation adjustment in the same manner as the ATCC quality control strain. Satisfactory medium performance can obviously be assured by biological means in aminoglycoside susceptibility testing of Pseudomonas aeruginosa on Mueller-Hinton medium; however, cation adjustment of medium to predetermined levels of ionized calcium and soluble magnesium can now also provide desirable performance levels for P. aeruginosa on Mueller-Hinton medium.
Examination of major disagreements in susceptibility test results by Autobac-1 and MS-2
Authors: Lindsey N J , Barnes W G
Published: June 2012

Major disagreements between two automated susceptibility test instruments, Autobac-1 and MS-2, generated from 4,213 tests on 630 bacterial isolates, were analyzed. The major disagreement rate between the instruments was only 7.4%. The highest major disagreement rates for bacteria were with Staphylococcus epidermidis, enterococci, gram-positive bacilli, and Providencia species, and those for antibiotics were with ampicillin and penicillin G. With most other bacteria and antibiotics, the instruments disagreed at a rate less than 10% and frequently at a rate less than 4%. However, 32 specific bacterium-antibiotic combinations exceeded a 10% rate. Possible reasons for some of these higher disagreement rates are discussed. Reconciliation of instrument results with the standard agar disk diffusion result for each major disagreement revealed that about 15% were irreconcilable and, of the remaining 259, 177 agreed with MS-2 and 82 agreed with Autobac-1. Major disagreements between instruments seemed random, but there appeared to be tendencies, with certain bacteria and certain antibiotics, for MS-2 to detect susceptible reactions more consistently than resistant ones and for Autobac-1 to detect resistant reactions more consistently than susceptible ones.