bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetics of cefaclor in renal failure: effects of multiple doses and hemodialysis
Authors: Spyker D A , Gober L L , Scheld W M , Sande M A , Bolton W K
Published: June 2012

The pharmacokinetics of cefaclor were characterized in 15 functionally anephric patients on hemodialysis. Each patient received a 500-mg oral dose of cefaclor every 8 h for 10 days. Multiple serum drug levels were measured by bioassay on day 0 (no hemodialysis), day 10 during hemodialysis, and as single determinations 1 h after administration on days 1, 3, and 5. Analysis of cefaclor kinetics in these 15 patients along with kinetics from 24 previously studied patients showed that weight was the best single predictor of volume of distribution. The corrected creatinine clearance (calculated from serum creatinine, age, and sex) proved to be the best predictor of drug half-life (r = 0.969). Thus, a single serum creatinine test provided a better estimated of cefaclor half-life than a 24-h urine collection. Cefaclor was cleared with an average serum half-life of 2.9 h without hemodialysis and 1.5 h during hemodialysis. Cefaclor serum levels measured 1 h after administration on days 0, 1, 3, and 5 showed no evidence of accumulation. Thus, cefaclor may be administered orally in multiple doses without accumulation in functionally anephric patients. In patients on dialysis, dosage interval or quantity should be increased to compensate for doubled drug clearance dialysis.
Bactericidal activity of trimethoprim alone and in combination with sulfamethoxazole on susceptible and resistant Escherichia coli K-12
Authors: Amyes S G
Published: June 2012

The combined effects of trimethoprim and sulfamethoxazole on the viability of Escherichia coli K-12 and resistant strains possessing resistance plasmids were examined in minimal medium. When methionine, glycine, and adenine were present, sulfamethoxazole could enhance trimethoprim activity against E. coli K-12 so that the combination was bactericidal. However, this enhancement occurred over a narrow range of trimethoprim concentrations (0.04 to 0.2 mg liter-1) and only when the sulfamethoxazole concentration was more than 10 times that of trimethoprim. Under certain conditions, sulfamethoxazole enhanced trimethoprim bactericidal activity against E. coli K-12 carrying plasmid R1 at concentrations of sulfamethoxazole far below those required to inhibit the organism, but there was no such enhancement with the same host containing the SSu plasmid. Similar differences were found with strains possessing trimethoprim resistance plasmids R483 and R751. Sulfamethoxazole can promote a bactericidal response with trimethoprim in E. coli K-12 and some of its resistant derivatives, but only under a narrow range of concentrations.
Pharmacokinetics of ceforanide
Authors: Ripa S , La Rosa F , Ghezzi A , Prenna M , Pfeffer M
Published: June 2012

The pharmacokinetic of ceforanide, a new parenteral cephalosporin antibiotic, were examined at intravenous and intramuscular doses of 250, 500, and 1,000 mg in healthy male volunteers. Over the above dosing range, ceforanide pharmacokinetics were essentially linear, with plasma clearances varying from 2.2 to 2.5 liters/h. The best present overall estimate of the drug's half-life was 2.9 h. Intramuscular ceforanide was 100% bioavailable, Peak intravenous serum levels were 39, 71, and 135 micrograms/ml at the end of 30-min infusions of 250, 500, and 1,000 mg; after intramuscular injections of 250, 500, and 1,000 mg, the respective peak serum levels were 21, 38, and 69 micrograms/ml. From 80 to 85% of the above doses were eliminated as unchanged.
Lack of in vitro activity of cefoxitin, cefamandole, cefuroxime, and piperacillin against Chlamydia trachomatis
Authors: Bowie W R
Published: June 2012

Newer penicillins and cephalosporins are being evaluated in many infections. One of these infections, acute pelvic inflammatory disease, can be caused by Chlamydia trachomatis. This study demonstrated that cefoxitin, cefamandole, cefuroxime, and piperacillin had no effective in vitro activity against C. trachomatis.
Susceptibility of Shigella species to erythromycin
Authors: Greenberg R N , Pearson R D , Innes D J , Sauer K T , Halterman L D , Guerrant R L
Published: June 2012

Two of the most common causes of inflammatory enteritis are Campylobacter fetus subsp. jejuni and Shigella species. No single antimicrobial agent is recommended for treatment of both diseases. Erythromycin is used to treat C. fetus subsp. jejuni infections but has not been studied in shigellosis. For this reason, we determined the susceptibility of 22 strains of Shigella to erythromycin and found that Shigella species are susceptible to concentrations of erythromycin which are obtainable in stool.
Chloramphenicol inhibition of the bactericidal effect of ampicillin against Haemophilus influenzae
Authors: Rocco V , Overturf G
Published: June 2012

The effects of combinations of ampicillin and chloramphenicol against seven strains of Haemophilus influenzae type b (five beta-lactamase-negative and two beta-lactamase-positive strains) were evaluated by killing-kinetic methods. Growth of strains was assessed in modified Levinthal broth against an inoculum of 10(5) organisms per ml; colony counts were performed immediately and at 6 and 20 h postinoculation. Ampicillin and chloramphenicol were completely bactericidal at 20 h. reducing bacterial densities to 0 colony-forming units per ml at concentrations equivalent to the ampicillin inhibitory concentration and twofold the chloramphenicol inhibitory concentrations. Chloramphenicol at its inhibitory concentration or at one-half of its inhibitory concentration prevented the normally bactericidal activity of ampicillin at 20 h incubation, but not at 6 h.
Inhibitory effects of antiherpesviral thymidine analogs against varicella-zoster virus
Authors: Machida H , Kuninaka A , Yoshino H
Published: June 2012

Thymidine analogs highly active against herpes simplex virus were compared in their inhibitory action against seven strains of varicella-zoster virus by a plaque reduction assay. E-5-Bromovinyl-arabinosyluracil (BV-ara-U) was most active, followed by E-5 chlorovinyl-arabinosyluracil, E-5-bromovinyl-2'-deoxyuridine (BV-dUrd), 2'-fluoro-5-methyl-arabinosyluracil, 2'-fluoro-5-iodo-arabinosylcytosine, arabinosylthymine, 5-vinyl-arabinosyluracil, acycloguanosine, and 5-iodo-2'-deoxyuridine, in order to decreasing activity. BV-ara-U was more than 10 times as active as BV-dUrd and almost completely inhibited plaque development of five strains of varicella-zoster virus at a concentration as low as 1 ng/ml.
In vitro development of rifampin resistance in clinical isolates of Haemophilus influenzae type b
Authors: Yogev R , Melick C , Glogowski W
Published: June 2012

Although all of 14 clinical isolates of Haemophilus influenzae type b strains demonstrated rifampin susceptibility in vitro (minimal inhibitory concentration less than or equal to 0.4 microgram/ml) when an inoculum of 10(4) colony-forming units (CFU) was used, 10 of the 14 strains manifested resistance to this agent when an inoculum of 10(8) CFU was tested. The mutation rate for rifampin resistance ranged from 1 resistant colony per 3.5 x 10(6) CFU to 1 per 4 x 10(7) CFU. The emergence of rifampin-resistant mutants was prevented when trimethoprim was combined with rifampin. This finding suggests that when used alone for prophylaxis of H. influenzae type b nasopharyngeal carriers, rifampin is likely to lead to the emergence of resistant strains.
Inhibition of herpes simplex virus replication by succinyl concanavalin A
Authors: Garrity P , Szelc C , Paquette C , McEvoy M , Millette R , Adler R
Published: June 2012

Incubation of herpes simplex virus type 1-infected cells with succinyl-concanavalin A, a derivative of the jack bean lectin concanavalin A, resulted in the decreased production of virus. The mode of inhibition by the lectin was unclear. No effect was apparent on the level of viral DNA synthesis. However, incubation of infected cells with increasing concentrations of the lectin appeared to result in a decrease in the quantity of viral protein produced within the cell. A reduction in the virus titer of 57 to 64% was observed upon direct incubation of extracellular virus in the presence of 50 to 100 micrograms of succinyl-concanavalin A per ml.
Bacteriophage-mediated acquisition of antibiotic resistance by Staphylococcus aureus type 88
Authors: Schaefler S
Published: June 2012

Antibiotic-resistant Staphylococcus aureus strains of phage type 88, lysogenic for phage 188, when grown in mixed culture with a nonlysogenic novobiocin-resistant strain, acquired novobiocin resistance at a high rate from the nonlysogenic strain. With most strains of phage type 88, there was no detectable transfer of resistance from lysogenic to nonlysogenic cells. Lysogenization with phage 188 of phage-sensitive strains conferred on the lysogenized cells the ability to acquire chromosome and plasmid resistance markers. The acquisition of novobiocin resistance in liquid cultures depended on the aeration of the culture, cell density, and the presence of Ca2+. Pronase, and to a lesser degree other proteinases, increased the rate of acquisition of chromosome- and plasmid-determined resistance markers by cells lysogenic for phage 188.
Emergence of rifampin-resistant Haemophilus influenzae
Authors: Nicolle L E , Postl B , Kotelewetz E , Albritton W , Harding G K , Bourgault A M , Ronald A R
Published: June 2012

Rifampin susceptibility of nasopharyngeal Haemophilus influenzae strains was determined before and after community-wide chemoprophylaxis with rifampin (children) and sequential minocycline-rifampin (adults). All strains were rifampin susceptible before prophylaxis, but 10.3% of the strains at 1 week and 7.5% of the strains at 9 weeks after prophylaxis were rifampin resistant.
Antimicrobial and beta-lactamase inhibitory activities of carpetimycins A and B, new carbapenem antibiotics
Authors: Kobayashi F , Saino Y , Koshi T , Hattori Y , Nakayama M , Iwasaki A , Mori T , Mitsuhashi S
Published: June 2012

Carpetimycins A and B showed widely broad spectra and potent activity against gram-positive and gram-negative bacteria, including various species of anaerobic bacteria. The antimicrobial activity of carpetimycin A was 8 to 64 times greater than that of carpetimycin B and 4 to 128 times greater than that of cefoxitin. The inhibitory concentration of carpetimycin A required to inhibit more than 90% of clinical isolates was 0.39 micrograms/ml for Escherichia coli and klebsiella and 1.56 microgram/ml for Proteus and Staphylococcus aureus. At a concentration of 3.13 micrograms/ml, carpetimycin A inhibited almost all clinical isolates of Enterobacter and Citrobacter, which showed resistance to many clinically used beta-lactam antibiotics. Carpetimycins A and B furthermore were shown to have potent inhibitory activities against several kinds of beta-lactamases produced by beta-lactam-resistant strains; they inhibited not only penicillinase-type beta-lactamases but also cephalosporinase-type beta-lactamases, which were insensitive to clavulanic acid. In combination with beta-lactam antibiotics such as ampicillin, carbenicillin, and cefazolin, carpetimycins A and B showed synergistic activities against beta-lactam-resistant bacteria.
Alpha interferon and acyclovir treatment of herpes simplex virus in lymphoid cell cultures
Authors: Hammer S M , Kaplan J C , Lowe B R , Hirsch M S
Published: June 2012

The T-lymphoblastoid cell line CEM, persistently infected with herpes simplex virus type 1, has been used to examine the antiviral efficacy of human alpha interferon and acyclovir, both alone and in combination. Acyclovir and interferon each produced dose-dependent decreases in virus titer at concentration ranges of 1 to 100 microM (approximately 0.225 to 22.5 micrograms/ml) and 10 to 10,000 U/Ml, respectively. Mean reductions in titer of 1.9 and 4.2 log10 PFU/ml were observed with 100 microM acyclovir and 10,000 U of interferon per ml, respectively, on day 10 of treatment. The combination of 100 microM acyclovir and 10,000 U of interferon per ml produced the most rapid fall in virus titer of all regimens examined and elimination of infections virus by day 7. Prolonged treatment (greater than 10 days) with acyclovir or alpha interferon was accompanied by a gradual return of virus titer to control levels despite the continuous presence of drug. Virus preparations isolated from such cultures were tested for antiviral agent sensitivity by a plaque reduction method. Acyclovir-exposed isolates were found to be acyclovir resistant, with 50% inhibitory doses of greater than 200 microM, and to be thymidine kinase deficient. Alpha interferon-exposed isolates were not interferon resistant. These results suggest that, in persistently herpes simplex virus-infected CEM cells: (i) combination treatment with 100 microM acyclovir and 10,000 U of alpha interferon per ml is more effective in reducing virus titer than either agent alone; (ii) prolonged exposure to drug may result in development of resistance by either the virus strain or the host cell system; and (iii) development of acyclovir resistance by herpes simplex virus in lymphoid cells is mediated by thymidine kinase.
Clindamycin therapy of experimental Staphylococcus aureus endocarditis
Authors: Scheld W M , Johnson M L , Gerhardt E B , Sande M A
Published: June 2012

The efficacy of clindamycin in the treatment of experimental endocarditis in rabbits was compared with that of nafcillin. Both drugs were administered intramuscularly three times daily for 5 days, clindamycin at doses of 6.25, 12.5, 25, or 50 mg/kg and nafcillin at a dose of 200 mg/kg. The minimum inhibitory and bactericidal concentrations (0.125 microgram/ml) of clindamycin for the test strain of Staphylococcus aureus were very similar to the corresponding concentrations (0.25 microgram/ml) of nafcillin. The effectiveness of clindamycin against the experimental endocarditis was dose dependent. The therapeutic accomplishments of the two highest clindamycin doses were equivalent to those attained with 200 mg of nafcillin per kg. The rates of sterilization of vegetations were equal when the serum bactericidal titers of these drugs were greater than or equal to 1:8. In special situations the administration of clindamycin in high doses could prove useful in the treatment of S. aureus endocarditis.
Effects of clofazimine alone or combined with dapsone on neutrophil and lymphocyte functions in normal individuals and patients with lepromatous leprosy
Authors: van Rensburg C E , Gatner E M , Imkamp F M , Anderson R
Published: June 2012

The effects of clofazimine on neutrophil activities such as random motility, migration to the leukoattractants endotoxin-activated serum and N-formyl-L-methionyl-L-leucyl-L-phenylalanine phagocytosis of Candida albicans, postphagocytic hexose-monophosphate shunt activity, and myeloperoxidase-mediated iodination and the effects of clofazimine on lymphocyte transformation to mitogens were assessed in vitro and after ingestion of the drug by normal individuals and patients with lepromatous leprosy. For in vitro studies, the concentration range of the drug investigated was 10(-6) M to 10(-2) M. for in vivo studies, subjects ingested 200 mg of clofazimine daily for a period of 5 days. At concentrations of 5 X 10(-6) M to 5 X 10(-3) M clofazimine caused a progressive dose-dependent inhibition of neutrophil motility without detectable effects on phagocytosis, postphagocytic hexose-monophosphate shunt activity, or myeloperoxidase-mediated iodination. Over the same concentration range, clofazimine inhibited lymphocyte transformation. The inhibitory effect on neutrophil motility was associated with a spontaneous stimulation of oxidative metabolism and could be prevented by coincubation of dapsone with clofazimine. after ingestion of clofazimine responsiveness of lymphocytes to mitogens was decreased in normal volunteers and leprosy patients: neutrophil motility in normal individuals was likewise inhibited.
High-performance liquid chromatographic method for determination of cefmetazole in human serum
Authors: Sekine M , Sasahara K , Kojima T , Morioka T
Published: June 2012

A fast, specific, sensitive high-performance liquid chromatographic method for the determination of cefmetazole in human serum was developed. The serum samples were deproteinized by adding 5% trichloroacetic acid in methanol containing barbital as an internal standard and were injected onto a reverse-phase column (mu-Bondapak C18) with a mobile phase of 10 to 15% acetonitrile in 0.005 M citrate buffer (pH 5.4). Eluted components were detected by UV absorption at 254 nm. Cefmetazole and the internal standard were separated from interfering serum components by this method. The peak height ratio of cefmetazole to the internal standard was proportional to the cefmetazole concentration in the range from 0.4 to 100 micrograms/ml. Serum samples obtained from three patients after a single intravenous injection of cefmetazole were assayed by this method and by a microbiological method. There was a good correlation between two assay methods (correlation, coefficient, 0.98). The stability of cefmetazole in human serum was (correlation coefficient, 0.98). The stability of cefmetazole in human serum was also determined by this method. Cefmetazole was stable in human serum for 2 weeks at 4 degrees C or for at least 8 weeks if it was kept frozen. As the high-performance liquid chromatography method is simple, specific, accurate, and reproducible, it appears to be more suitable for routine assay of cephalosporins than other assay methods.
In vitro susceptibility of cephalothin-resistant Enterobacteriaceae and Pseudomonas aeruginosa to Amikacin and selected new beta-lactam agents
Authors: McNamara B T , Meyer R D , Pasiecznik K A
Published: June 2012

Amikacin was evaluated in vitro by agar dilution testing against 148 different clinical isolates of cephalothin-resistant Enterobacteriaceae and Pseudomonas aeruginosa in parallel with cephalothin, cefoxitin, moxalactam, N-formimidoyl thienamycin, ceftriaxone, and cefmenoxime. Cefsulodin was also evaluated against 39 isolates of P. aeruginosa. More than 80% of all isolates tested were also gentamicin resistant, as determined by disk testing. Moxalactam and amikacin had comparable high activities against Proteus species, Escherichia coli, Serratia species, and Providencia species, and both amikacin and N-formimidoyl thienamycin had comparably high activities against the Klebsiella-Enterobacter group. N-Formimidoyl thienamycin was the most active agent against P. aeruginosa, followed by cefsulodin and amikacin.
S-Adenosyl-L-methionine: macrocin O-methyltransferase activities in a series of Streptomyces fradiae mutants that produce different levels of the macrolide antibiotic tylosin
Authors: Seno E T , Baltz R H
Published: June 2012

A series of mutants of Streptomyces fradiae selected for increased production of the macrolide antibiotic tylosin was analyzed for levels of expression of macrocin O-methyltransferase, the enzyme which catalyzes the final step in the biosynthesis of tylosin. Increased tylosin production was accompanied by increased macrocin O-methyltransferase in some of the mutants. Increased expression of macrocin O-methyltransferase was due to more rapid early biosynthesis of the enzyme, to reduced decay of enzyme specific activity late in the fermentation, or to combinations of both. Mutant strains which showed rapid loss of enzyme specific activity late in the fermentation converted large amounts of tylosin to relomycin. The most productive mutants, which synthesized elevated levels of macrocin O-methyltransferase, also produced large amounts of macrocin, the substrate for the enzyme. Incomplete conversion of macrocin to tylosin by these mutants may be due to substrate and product inhibition (E. T. Seno and R. H. Baltz, Antimicrob. Agents Chemother. 20:370-377, 1981). The results suggest that both the levels of precursors and the levels of expression of tylosin biosynthetic enzymes are important for efficient production of tylosin.
Erythromycin, carbomycin, and spiramycin inhibit protein synthesis by stimulating the dissociation of peptidyl-tRNA from ribosomes
Authors: Menninger J R , Otto D P
Published: June 2012

In mutant Escherichia coli with temperature-sensitive peptidyl-tRNA hydrolase (aminoacyl-tRNA hydrolase; EC 3.1.1.29), peptidyl-tRNA accumulates at the nonpermissive temperature (40 degrees C), and the cells die. These consequences of high temperature were enhanced if the cells were first treated with erythromycin, carbomycin, or spiramycin at doses sufficient to inhibit protein synthesis in wild-type cells but not sufficient to kill either mutant or wild-type cells at the permissive temperature (30 degrees C). Since peptidyl-tRNA hydrolase in he mutant cells is inactivated rapidly and irreversibly at 40 degrees C, the enhanced accumulation of peptidyl-tRNA and killing were the result of enhanced dissociation, stimulated by the antibiotics, of peptidyl-tRNA from ribosomes. The implications of these findings for inhibition of cell growth and protein synthesis are discussed. Certain alternative interpretations are shown to be inconsistent with the relevant data. Previous conflicting observations on the effects of macrolide antibiotics are explained in terms of our observations. We conclude that erythromycin, carbomycin, and spiramycin (and probably all macrolides) have as a primary mechanism of action the stimulation of dissociation of peptidyl-tRNA from ribosomes, probably during translocation.
Antibacterial activity of matrix-bound ovotransferrin
Authors: Valenti P , Antonini G , Fanelli M R , Orsi N , Antonini E
Published: June 2012

Ovotransferrin immobilized by covalent linkage to Sepharose 4B showed a bacteriostatic effect towards Escherichia coli similar to that of free ovotransferrin. The growth of the bacteria, after exposure to the gel-bound ovotransferrin and its removal, depended on the length of exposure. The results suggest that the antibacterial activity of transferrin is not due simply to the removal of iron from the medium.
Susceptibility of Nocardia asteroides to various antibiotics, including newer beta-lactams, trimethoprim-sulfamethoxazole, amikacin, and N-formimidoyl thienamycin
Authors: Gombert M E
Published: June 2012

The susceptibility of 26 isolates of Nocardia asteroides to several antibiotics was determined by the agar dilution technique. Many currently available beta-lactam antibiotics were ineffective. Cefotaxime, cefmenoxime, and N-formimidoyl thienamycin were active against these strains, with 80% minimal inhibitory concentrations of 4, 4, and 2 micrograms/ml, respectively. Amikacin was the most effective agent tested.
Susceptibilities of anaerobic bacteria to N-formimidoyl thienamycin (MK0787) and to other antibiotics
Authors: Kesado T , Watanabe K , Asahi Y , Isono M , Ueno K
Published: June 2012

The susceptibilities of 462 clinical anaerobic bacterial isolates to N-formimidoyl thienamycin and 16 other currently available and investigational antibiotics were determined by the agar dilution technique. N-Formimidoyl thienamycin was significantly more active than the reference antibiotics against most organisms tested, especially Bacteroides sp., including clindamycin-resistant strains. All 462 isolates were inhibited by 4 micrograms of N-formimidoyl thienamycin per ml, and no resistant strains were found in the species tested. N-Formimidoyl thienamycin was less active (i.e., had a higher 50% minimal inhibitory concentration) against Fusobacterium sp. than clindamycin, SM-1652, and piperacillin, and less active against Clostridium difficile than metronidazole, but was equally active or more active than the other reference antibiotics tested.
Prophylactic activity of intranasal enviroxime against experimentally induced rhinovirus type 39 infection
Authors: Hayden F G , Gwaltney J M
Published: June 2012

Intranasal administration of enviroxime by aerosol spray was associated with drug levels in nasal secretions that 1 h later averaged 750-fold higher than those inhibitory for rhinoviruses in vitro (0.2 microgram/ml). However, administration of intranasal enviroxime (one spray per nostril, five times per day) to susceptible volunteers, beginning 1 day before and continuing for 4 days after virus exposure, did not significantly reduce infection or illness due to experimentally induced rhinovirus type 39 infection. The combined results of two separate trials yielded an infection rate of 100% for 21 placebo-treated and 89% for 19 enviroxime-treated subjects. Approximately one-half of the volunteers in each group had seroconversion to the challenge virus. Overall, 52% of the placebo-treated and 53% of the enviroxime-treated subjects developed colds. No significant differences in symptom scores, nasal mucus weights, or numbers of nasal tissues used were observed between the two groups. Two-thirds of the enviroxime-treated volunteers noted intranasal irritation immediately after sprays, as compared with only one-third of the placebo-treated subjects.
In vitro activity of apalcillin compared with that of other new penicillins and anti-Pseudomonas cephalosporins
Authors: Neu H C , Labthavikul P
Published: June 2012

Apalcillin, a naphthydridine derivative of ampicillin, was compared with ticarcillin, azlocillin, mezlocillin, piperacillin, cefotaxime, and cefoperazone against gram-negative and gram-positive bacterial isolates and with cefsulodin and tobramycin against Pseudomonas aeruginosa. The minimal concentrations of apalcillin at which 50 and 90% of hospital isolates of Escherichia coli were inhibited were similar to those of mezlocillin and piperacillin (1.6 and 100 micrograms/ml, respectively). Apalcillin had minimal inhibitory concentrations similar to those of piperacillin against Citrobacter freundii and Citrobacter diversus. Against Klebsiella, apalcillin inhibited 50% of organisms at a concentration of 6.3 micrograms/ml, similar to piperacillin. The activity of apalcillin against Enterobacter (E. aerogenes, E. cloacae, and E. agglomerans) was similar to that of mezlocillin and piperacillin and greater than that of ticarcillin. The activity of apalcillin against Proteus mirabilis was similar to that of the other agents, as was its activity against indole-positive Proteus and Providencia. Only 40% of Serratia were inhibited at an apalcillin concentration of 25 micrograms/ml. Apalcillin was as active as piperacillin but twofold less active than cefoxitin or moxalactam against Bacteroides fragilis. It was as active as piperacillin, cefoperazone, and cefsulodin against P. aeruginosa (apalcillin inhibited 90% of organisms at a concentration of 25 mg/ml). There was an inoculum effect and a difference in the minimal inhibitory concentration and minimal bactericidal concentration with beta-lactamase strains. Apalcillin was hydrolyzed by plasmid beta-lactamase but not as well by cephalosporinases.
Effect of ketoconazole on isolated mitochondria from Candida albicans
Authors: Shigematsu M L , Uno J , Arai T
Published: June 2012

Ketoconazole, an oral antimycotic imidazole drug, blocked the transport of electrons in the respiratory chain of Candida albicans under aerobic conditions with different substrates, such as NADH and succinate. This effect was a nonspecific inhibition of NADH oxidases and succinate oxidases. The addition of ketoconazole to C. albicans mitochondria without a substrate resulted in strong reduction of cytochrome a3, as revealed by difference spectra (reduced versus oxidized). This indicated that there was a specific interaction between ketoconazole and cytochrome c oxidase. A spectrophotometric analysis confirmed that the cytochrome oxidases other than cytochrome c oxidase were not inhibited because subsequent addition of any substrate caused an increased level of reduction of all of the other respiratory chain components compared with the control. Consequently, our data strongly suggested that the primary site of ketoconazole inhibition on isolated mitochondria from C. albicans is the most distal portion of the respiratory chain.
Comparative in Vitro Activities of Cefmenoxime (SCE-1365) and Newer Cephalosporin Derivatives of Clinical Utility
Authors: Ahonkhai Vincent I. , Cherubin Charles E. , Shulman Michael A. , Bancroft Ursula
Published: June 2012

The minimal inhibitory concentrations of cefmenoxime (SCE-1365), cefotaxime, cefoperazone, and moxalactam against various species of aerobic bacteria were determined. The activities of cefmenoxime, cefotaxime, and moxalactam were generally similar and slightly higher than the activity of cefoperazone.
Activities of Four Aminoglycosides at Subbactericidal Concentrations
Authors: Schrire Leonard , Robinson Roy G. , Doehring Richard O. , Koornhof Hendrik J.
Published: June 2012

This report describes an activity range index derived from the minimal bactericidal and antibiotic concentrations of four aminoglycosides against four representatives of clinically important gram-negative bacilli. The ranking orders of in vitro activity differed from those using the minimal bactericidal concentration or the minimal antibiotic concentration as the sole criterion.
In vitro activity of antibiotics commonly used in the treatment of otitis media against Streptococcus pneumoniae isolates with different susceptibilities to penicillin
Authors: Tarpay M M , Welch D F , Salari H , Marks M I
Published: June 2012

Susceptibilities of 82 clinical isolates of Streptococcus pneumoniae, including 25 from the middle-ear fluid, were evaluated against antibiotics commonly used in the treatment of acute otitis media. Potentially significant resistance occurred in 6% of the isolates to erythromycin and an erythromycin-sulfisoxazole combination. The combination of trimethoprim and sulfamethoxazole was synergistic for 95% of the isolates. Only 2.5% of all of the isolates were resistant to both erythromycin-sulfisoxazole and trimethoprim-sulfamethoxazole. The presently used drug regimens should be effective against the majority of S. pneumoniae isolates in otitis media.
Activity of Cefoperazone Against Ampicillin-Resistant Bacteria in Agar and Broth Dilution Tests
Authors: Kayser Fritz H. , Morenzoni Giovanna , Homberger Françoise
Published: June 2012

Examination of the activity of cefoperazone against ampicillin-resistant, gramnegative bacteria in agar dilution and simultaneously in broth dilution revealed that strains could be divided into three classes: class I strains were susceptible in agar (mean minimal inhibitory concentration [MIC], 0.5 mg/liter) as well as in broth dilution (mean MIC, 1.5 mg/liter), class II strains were susceptible in agar (MIC, 0.9 mg/liter), but resistant in broth dilution (MIC, 182 mg/liter); and class III strains were highly resistant in both test systems. Among 100 randomly selected ampicillin-resistant
Escherichia coli
cultures, 51 belonged to class I and 49 belonged to class II. Class III
E. coli
strains were much rarer. Similar results were obtained with cefamandole and cephalothin, but not with six other second-and third-generation cephalosporins. MICs of cefoperazone against cultures of all three classes were influenced by initial inoculum size. The inoculum effect was greatest with class II strains. Examination of bactericidal activity by cefoperazone showed killing of class I and class II
E. coli
strains and of class III strains of other genera during the first hours of incubation and regrowth after the drug was destroyed by the action of TEM β-lactamase (penicillinase). Representative class I bacteria produced 10 to 100 times less TEM β-lactamase than did class II strains. It appeared that the quantitative difference in TEM production was the reason for the different resistance phenotypes in class I and class II strains.
Salmonella
and
Klebsiella
strains of class III produced the same amounts of TEM β-lactamase as did class II
E. coli
strains. Probably, some factors other than β-lactamase contributed to the class III phenotype in these species.
Single- and multiple-dose pharmacokinetics of moxalactam in normal subjects
Authors: Israel K S , Black H R , Brier G L , Wolny J D , DeSante K A
Published: June 2012

The pharmacokinetics of moxalactam were studied in 86 normal adult male volunteers who received single or multiple doses intravenously or intramuscularly. The short absorption half-times and lag times indicate that the intramuscular dose is rapidly absorbed. The mean plasma half-life was 1.85 +/- 0.24 h for intravenous doses and 2.24 +/- 0.44 h for intramuscular doses. The mean renal clearances for intravenous doses were 0.052 and 0.067 liters/kg per h for intramuscular doses. Although moxalactam is eliminated primarily by the kidney a chromatogram of the feces from volunteers who received multiple doses showed that it is also excreted as the parent compound in to the feces via the biliary tract. The pharmacokinetics parameters of moxalactam when administered intravenously or intramuscularly in single and multiple doses clearly show the kinetics of moxalactam are linear over the dosage ranges studied and are independent of dose.
Effects of ampicillin plus sulbactam on bowel flora in patients undergoing colorectal surgery
Authors: Kager L , Liljeqvist L , Malmborg A S , Nord C E , Pieper R
Published: June 2012

The influence of a combination of ampicillin and a beta-lactamase inhibitor, sulbactam, on colonic bacterial flora was studied in patients undergoing colorectal surgery. Drug concentrations were determined in serum, intestinal mucosa, and feces. The results of the drug concentrations were correlated with changes in the numbers of aerobic and anaerobic bacterial bowel flora. Ampicillin and sulbactam were given intravenously to 21 patients in 500-mg doses of each drug every 8 h for 2 days. The first dose was given when anesthesia was begun. The concentrations of ampicillin in serum were significantly higher (0.01 greater than P greater than 0.001) than those of sulbactam. In contrast, at all time intervals, the concentrations of sulbactam in intestinal mucosa were significantly higher than those of ampicillin (0.05 greater than P greater than 0.01). The serum half-life of the two drugs was the same at 2.2 h. After one dose of the antibiotics, sulbactam was detectable in the feces of four patients, and ampicillin was detectable in the feces of 11 patients. During the 2 days of ampicillin and sulbactam prophylaxis, no measurable decrease occurred in the anaerobic flora of the bowel; a mean decrease of 3 logs occurred in the anaerobic bowel flora. The results of this study show that ampicillin and sulbactam prophylaxis had a greater effect on the anaerobic bowel flora than on the aerobic bowel flora. In light of the in vitro spectrum of ampicillin and sulbactam activity, it was surprising that bowel aerobic flora was unchanged.
Effects of erythromycin in combination with penicillin, ampicillin, or gentamicin on the growth of Listeria monocytogenes
Authors: Penn R L , Ward T T , Steigbigel R T
Published: June 2012

Since the optimal antimicrobial therapy for infections caused by Listeria monocytogenes, particularly in patients allergic to penicillin, is uncertain, we investigated the in vitro effects of erythromycin, alone and in combination with other antibiotics, on listeriae. Seven strains of listeriae were inhibited but not killed by erythromycin, penicillin G, or ampicillin when tested by a microtiter broth dilution method. Susceptibility to gentamicin decreased when tryptose phosphate broth was substituted for Mueller-Hinton broth, but was independent of their calcium and magnesium concentrations. Quantitative killing studies performed with erythromycin combined with either penicillin G or ampicillin yielded antagonism for all strains, in contrast to microtiter checkerboard determinations, which did not indicate antagonism in all instances. Antagonism occurred with strains in both the stationary and log phases of growth and was slightly reversed by a 120-min preincubation of the listeriae with penicillin before the addition of erythromycin. Erythromycin and gentamicin were antagonistic in quantitative killing studies. Based on these in vitro findings, we conclude that the addition of gentamicin to erythromycin offers no advantage in the treatment of listeriosis in the penicillin-allergic patient.
Comparative efficacies of ceftriaxone, moxalactam, and ampicillin in experimental Salmonella typhimurium infection
Authors: Anton P A , Kemp J A , Butler T , Jacobs M R
Published: June 2012

The activities of ceftriaxone, moxalactam, and ampicillin against Salmonella typhimurium LT-2 were compared in culture media at pH 5, 6, 7 and 8 and in mice inoculated intraperitoneally. The minimal inhibitory concentrations for strain LT-2 in Mueller-Hinton broth were 0.03 microgram of ceftriaxone per ml, 0.08 microgram of moxalactam per ml, and 0.4 microgram of ampicillin per ml. A comparison of minimal inhibitory concentrations in buffered broth at pH 5 with those in media at higher pH values showed that ceftriaxone was more acid stable than the other antibiotics. Groups of CF-1 female mice inoculated intraperitoneally with 3 X 10(4) colony-forming units received saline or each drug in fourfold decremental doses by the subcutaneous route every 8 h for 3 days, beginning at 24 h after challenge. The mean log 10 colony-forming units of S. typhimurium per spleen at the end of treatment and the mortality rates at 21 days after inoculation were measured for each treatment group. The mean log 10 colony-forming units per spleen was significantly reduced from that of the saline control by dosages of greater than or equal to 0.06 mg of ceftriaxone per kg, 64 mg of moxalactam per kg, or greater than or equal to 16 mg of ampicillin per kg (P less than 0.05). Mortality rates of infected mice were significantly reduced by dosages of greater than or equal to 1 mg of ceftriaxone per kg or greater than or equal to 64 mg of ampicillin per kg (P less than 0.05), whereas moxalactam in dosages as high as 16 mg/kg did not significantly reduce mortality rate. These results demonstrate the superiority of ceftriaxone to the other tested antibiotics on a weight basis in this model of experimental Salmonella infection.
Activities of amoxicillin and clavulanic acid combinations against urinary tract infections
Authors: Crokaert F , van der Linden M P , Yourassowsky E
Published: June 2012

Urinary tract infection caused by beta-lactamase-producing bacteria were treated with 500 mg of amoxicillin three times daily plus either 250 or 125 mg of clavulanic acid three times daily. The overall cure rate was 63.6%, 77.7% with the high dose of clavulanic acid and 53.8% with the low dose. Gastrointestinal intolerance was common in the high-dose clavulanic acid regimen.
Pharmacokinetics of amoxicillin and clavulanic acid administered alone and in combination
Authors: Adam D , de Visser I , Koeppe P
Published: June 2012

The pharmacokinetics of amoxicillin and clavulanic acid, administered alone and in combination, were studied in six male and six female normal human volunteers. Each ingested 500 mg of amoxicillin or 125 mg of clavulanic acid or the above agents in combination in randomized sequences. The results indicate that most of the parameters tested for either substance are essentially independent of the presence of the other one.
Plasmid-mediated gentamicin resistance of Pseudomonas aeruginosa and its lack of expression in Escherichia coli
Authors: Kato T , Sato Y , Iyobe S , Mitsuhashi S
Published: June 2012

We isolated 11 nonconjugative plasmids mediating resistance to aminoglycoside antibiotics, including gentamicin, from Pseudomonas aeruginosa strains. Their genetic properties were investigated in both P. aeruginosa and Escherichia coli transformants. The plasmid molecular weights ranged from 11 x 10(6) to 24 x 10(6). A low level or complete absence of gentamicin resistance was observed when these plasmids were introduced into E. coli, but gentamicin resistance was restored when the plasmids were transferred back to P. aeruginosa from E. coli. Aminoglycoside-modifying enzyme activity was detected in P. aeruginosa harboring these plasmids, but was absent or greatly reduced in E. coli strains. This lack of expression may explain the observed decrease in aminoglycoside resistance.
Factors influencing detection of tolerance in Staphylococcus aureus
Authors: Goessens W H , Fontijne P , Michel M F
Published: June 2012

The phenomenon of tolerance to cloxacillin and methicillin was studied in Staphylococcus aureus. It was demonstrated that the minimal bactericidal concentrations showed marked differences, depending on the method of detection used. These differences resulted from carry-over of the antibiotic to the subculture plates. When carry-over of the antibiotic was prevented by the addition of beta-lactamase to the nutrient medium, the antibiotics were no longer bactericidal. At a certain antibiotic concentration and at higher concentrations, however, each strain showed a certain survival percentage after 24 h. The tolerance percentage was determined for 15 strains. The values found for the individual strains ranged from less than 0.1 to 11% for cloxacillin and methicillin. since these percentages were reproducible within narrow limits, they could be regarded as a characteristic of the strains. The tolerance percentage was independent of the growth phase of the initial cultures.
Activity of cefoperazone and two beta-lactamase inhibitors, sulbactam and clavulanic acid, against Bacteroides spp. correlated with beta-lactamase production
Authors: Crosby M A , Gump D W
Published: June 2012

A total of 102 isolates of Bacteroides spp. were studied for beta-lactamase production and susceptibility to cefoperazone alone or in combination with either of the beta-lactamase inhibitors sulbactam and clavulanic acid. The geometric mean minimal inhibitory concentration of cefoperazone alone was 31.5 micrograms/ml and when combined with 10 micrograms of sulbactam per ml or 2 micrograms of clavulanic acid per ml was reduced to 5.4 and 9.2 micrograms/ml, respectively. When bacterial suspensions were tested for beta-lactamase production with nitrocefin, 91 (89.2%) of these isolates produced the enzyme. The geometric mean minimal inhibitory concentrations of cefoperazone rose only slightly for isolates with low or intermediate enzyme activity but rose significantly for those with high activity. The addition of EDTA to cefoperazone significantly more frequently enhanced the activity of cefoperazone against beta-lactamase-negative as opposed to beta-lactamase-positive isolates. Furthermore, EDTA resulted in synergistic activity of the cefoperazone-sulbactam combination on beta-lactamase-positive isolates for which the combination had previously not shown a synergistic effect. This study demonstrates the relationship between beta-lactamase production and the resistance of Bacteroides spp. to cefoperazone and shows that inhibition of these enzymes can reverse this resistance.
Comparative activities of N-formimidoyl thienamycin, ticarcillin, and tobramycin against experimental Pseudomonas aeruginosa pneumonia
Authors: Pennington J E , Johnson C E
Published: June 2012

The therapeutic efficacies of disodium ticarcillin, tobramycin sulfate, and N-formimidoyl thienamycin (MK0787) were compared in guinea pigs with experimentally induced Pseudomonas aeruginosa pneumonia. Survival rates were 35% for ticarcillin, 80% for tobramycin, and 75% for N-formimidoyl thienamycin. Numbers of viable Pseudomonas organisms in lungs approximately 3 h after the first dose of drug were nearly 10-fold fewer in tobramycin- or N-formimidoyl thienamycin-treated animals than in ticarcillin-treated animals. Our data suggest that N-formimidoyl thienamycin may have therapeutic efficacy against respiratory infections with P. aeruginosa equivalent to that of tobramycin.
Interaction of azthreonam and related monobactams with beta-lactamases from gram-negative bacteria
Authors: Bush K , Freudenberger J S , Sykes R B
Published: June 2012

Monobactams containing 3 beta-aminothiazolyl oxime side chains (SQ 81,377, SQ 81,402, azthreonam, and SQ 26,917) have poor affinities for the broad-spectrum beta-lactamases TEM-2 and K1. Addition of a 4-methyl substituent significantly increased stability to hydrolysis by these enzymes. P99 cephalosporinase from Enterobacter cloacae was strongly inhibited by the monobactams. Interaction of azthreonam with the P99 enzyme in equimolar concentrations resulted in a single covalent complex which retained less than 3% catalytic activity. On incubation, enzymatic activity was slowly regained. Chromatographic studies of the incubation mixtures revealed the presence of a single ring-opened product. It is concluded that monobactams act as poor substrates for broad-spectrum beta-lactamases and tight-binding competitive substrates for the P99 beta-lactamase.
Capacity of deoxycytidine to selectively antagonize cytotoxicity of 5-halogenated analogs of deoxycytidine without loss of antiherpetic activity
Authors: Fox L M , Mekras J A , Bagwell C B , Greer S B
Published: June 2012

Enzyme kinetic studies from this laboratory (M. Dobersen and S. Greer, Biochemistry 17:920-928, 1978) suggested that deoxycytidine could antagonize the toxicity of 5-halogenated analogs of deoxycytidine without interfering with their antiviral activity. Antagonism by deoxycytidine of the toxicity of 5-chlorodeoxycytidine without impairing its anti-herpes simplex virus type 2 activity is demonstrated in the present studies. Tetrahydrouridine, an inhibitor of cytidine deaminase, was utilized. The high Km for deoxycytidine (0.6 mM) with respect to the herpes pyrimidine nucleoside kinase as compared with the low Km for 5-chlorodeoxycytidine (1.1 microM) accounts for the absence of antagonism of the antiviral activity. The high Km for 5-chlorodeoxycytidine (56 microM) as compared with the low Km of deoxycytidine (2 microM) with respect to mammalian deoxycytidine kinase accounts, in great part, for the antagonism of toxicity. In addition, antagonism of toxicity by deoxycytidine is the result of factors other than the kinetic parameters of nucleoside kinases, as indicated by its antagonism of the cytotoxicity of 5-chlorodeoxyuridine. This may be attributed to replenishment of low dCTP pools, diminished because of effector inhibition of ribonucleoside diphosphate reductase by Cl-dUTP. Resistance of the herpes-encoded enzymes to effector control may also play a role in the selective antagonism. Cell culture studies with high concentrations of tetrahydrouridine and 2'-deoxytetrahydrouridine suggest that competition by deoxycytidine for deaminases may not play a major role. The fact that deoxycytidine antagonizes the toxicity of chlorodeoxyuridine also argues against competition for the deaminases as a major reason for its effect. Limited studies with a topical herpes simplex virus type 2 infection system indicate heightened efficacy of 5-chlorodeoxycytidine (and tetrahydrouridine) when deoxycytidine is coadministered. The concepts of selective antagonism of a chemotherapeutic agent derived from these studies may be applied to other approaches that extent beyond viral chemotherapy.