bluuebunny/crossref_metadata_2025 huggingface dataset:
Randomized, prospective, and double-blind trial of new beta-lactams in the treatment of appendicitis
Authors: Lau W Y , Fan S T , Chu K W , Suen H C , Yiu T F , Wong K K
Published: June 2012

A prospective, randomized, and double-blind study was conducted with 864 patients operated on for appendicitis. In early cases, including normal and acute appendicitis, one dose of antibiotic was given. The rate of postappendectomy septic complications in patients who received cefotaxime, cefoperazone, or moxalactam was very low (about 3%), and there was no statistical difference between the drugs. For late cases, including gangrenous and perforated appendicitis, the antibiotics were continued for 5 days. Moxalactam decreased significantly the septic complications in these patients when compared with the other two drugs. It is safe, free from serious toxic side effects, and more convenient and easier to administer than combination antibiotic therapy. The main disadvantage of moxalactam is its high cost, but this has to be balanced against the savings in nursing time, the cost of monitoring renal function and serum level when aminoglycosides are used, and the reduced usage and manipulation of infusion sets.
Antimicrobial activity of aridicins, novel glycopeptide antibiotics with high and prolonged levels in blood
Authors: Grappel S F , Giovenella A J , Phillips L , Pitkin D H , Nisbet L J
Published: June 2012

Three new glycopeptide antibiotics, aridicins A, B, and C, produced by Kibdelosporangium aridum have a spectrum of antimicrobial activity in vitro which is similar to that of vancomycin. The antimicrobial activities of these glycopeptides against clinical bacterial isolates were compared with those of vancomycin and other related glycopeptide antibiotics in vitro by agar dilution and microtiter broth dilution tests and in vivo in mouse protection studies. In vitro they were somewhat less effective than vancomycin against strains of Staphylococcus aureus and less active against coagulase-negative Staphylococcus spp. However, they were more active than vancomycin against strains of Streptococcus faecalis and markedly superior to vancomycin and other glycopeptide antibiotics against strains of Clostridium difficile. In experimental infections, aridicin A was effective against strains of S. aureus, S. epidermidis, Streptococcus faecalis, and Streptococcus pyogenes, although its 50% effective doses were higher than those of vancomycin when administered after infection. After subcutaneous administration, aridicin A had a higher peak level in serum and a longer half-life than vancomycin or teicoplanin. The aridicins were markedly superior to vancomycin when administered prior to infection in mouse protection tests, indicating long-acting potential.
Susceptibility of Campylobacter jejuni and Campylobacter coli to macrolides and related compounds
Authors: Elharrif Z , Mégraud F , Marchand A M
Published: June 2012

The susceptibility of 105 thermophilic campylobacters from human and swine origins to eight macrolides and related compounds was tested. Erythromycin, josamycin, clindamycin, and ASE 136 BS (a new erythromycin derivative) were the most active against the human strains. The swine strains were highly resistant, except to pristinamycin. The human Campylobacter coli strains (except for two strains) behaved like the C. jejuni strains.
Susceptibility of Campylobacter species to nalidixic acid, enoxacin, and other DNA gyrase inhibitors
Authors: Taylor D E , Ng L K , Lior H
Published: June 2012

Nalidixic acid-resistant mutants of Campylobacter jejuni and C. coli as well as "C. laridis" strains showed cross-resistance to another DNA gyrase subunit A inhibitor, enoxacin (MIC, 32 micrograms/ml), whereas C. fetus subsp. fetus, C. fetus subsp. venerealis, and "C. hyointestinalis" strains were all susceptible to enoxacin (MIC, less than or equal to 2 micrograms/ml). All Campylobacter species were resistant to novobiocin (MIC, 32 to 512 micrograms/ml), but most strains were susceptible to the other DNA gyrase subunit B inhibitors coumermycin A1 and clorobiocin.
Stability of imipenem in Mueller-Hinton agar stored at 4 degrees C
Authors: Turgeon P L , Desrochers C
Published: June 2012

The purpose of the present study was to measure the stability of imipenem in Mueller-Hinton agar stored at 4 degrees C over time. MICs for Staphylococcus aureus ATCC 25923, Streptococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, and Pseudomonas aeruginosa ATCC 27853 were determined in triplicate daily for up to 15 days. The calculated mean time to observe a shift of one dilution in MIC endpoints was 4.33 +/- 1.25 days. For routine work, imipenem agar dilution plates should be prepared within 48 to 72 h of the test.
Method of testing the susceptibility of Pneumocystis carinii to antimicrobial agents in vitro
Authors: Cushion M T , Stanforth D , Linke M J , Walzer P D
Published: June 2012

Rat Pneumocystis carinii grown on lung-derived cell lines in tissue culture flasks and multiwell plates was tested for susceptibility to four antimicrobial agents currently being used in the treatment of human pneumocystosis. Standard criteria for organism quantitation, replication, viability, and inoculum size were established. Trimethoprim-sulfamethoxazole inhibited P. carinii growth at a concentration ratio of 1:19 microgram/ml, and pentamidine isethionate was active at 0.1 microgram/ml. alpha-Difluoromethylornithine, an inhibitor of polyamine biosynthesis, inhibited P. carinii at a concentration of 1 mM once erythrocytes (which are high in polyamine content) were removed from the inoculum; this effect could be overcome by the polyamine putrescine. Dapsone suppressed P. carinii replication at a dose of 0.1 microgram/ml, but this effect was lost after 72 h in culture. Overall, the reduction in P. carinii numbers with these drugs was relatively modest (45 to 84%), which is consistent with their lack of lethal effects on the organism in vivo. Thus, the system presented here should be helpful in developing new anti-P. carinii agents and in elucidating their mechanism of action.
Comparison of the in vitro activities of teicoplanin and vancomycin against Clostridium difficile and their interactions with cholestyramine
Authors: Pantosti A , Luzzi I , Cardines R , Gianfrilli P
Published: June 2012

The in vitro activity of teicoplanin was compared with that of vancomycin against fecal isolates of Clostridium difficile. All strains were susceptible to both antibiotics, but teicoplanin was fourfold more active than vancomycin. Cholestyramine was found to bind teicoplanin almost completely, reducing its activity to nondetectable levels.
Randomized evaluation of ceftazidime or ticarcillin and tobramycin for the treatment of osteomyelitis caused by gram-negative bacilli
Authors: Sheftel T G , Mader J T
Published: June 2012

Ceftazidime, a new cephalosporin with enhanced activity against aerobic gram-negative bacilli, was compared with tobramycin and ticarcillin in a randomized clinical trial. Efficacy and safety were evaluated in 18 patients (17 males, 1 female) with gram-negative osteomyelitis. All organisms were susceptible to the treatment antibiotics(s). There were nine patients treated with tobramycin and ticarcillin for 27 to 62 days (mean, 42 days), and nine patients were treated with 4 g of ceftazidime per day for 26 to 63 days (mean, 45 days). All nine patients receiving tobramycin and ticarcillin had the osteomyelitis arrested after the initial treatment. Follow-up was for 2 to 38 months (mean, 22 months). Of nine patients receiving ceftazidime three were initial treatment failures. Follow-up was for 13 to 31 months (mean, 21 months). A patient receiving ceftazidime had a transient rise in serum glutamic oxalacetic transaminase and serum glutamic pyruvic transaminase. There were three treatment failures in the ceftazidime group; no failures occurred in the group receiving the combination of ticarcillin and tobramycin. A larger series would be required to detect a significant difference between the two treatment groups.
Successful treatment of a pancreatic Nocardia asteroides abscess with amikacin and surgical drainage
Authors: Meier B , Metzger U , Müller F , Siegenthaler W , Lüthy R
Published: June 2012

A retroperitoneal Nocardia asteroides abscess was diagnosed in a 76-year-old patient. Trimethoprimsulfamethoxazole treatment for 6.5 weeks failed after surgical drainage of the abscess, and superinfection occurred. Subsequent treatment with amikacin resulted in a cure after 7 weeks. Amikacin might significantly shorten the duration of treatment in disseminated nocardiosis.
Effect of NaCl supplementation of Mueller-Hinton broth on susceptibility of staphylococci to aminoglycosides
Authors: Campos J M , Gill C J , Hare R S , Miller G H
Published: June 2012

The addition of NaCl to cation-supplemented Mueller-Hinton broth increased the MICs of gentamicin, amikacin, and netilmicin for coagulase-positive and -negative staphylococci in a concentration-dependent manner. At 2% NaCl, geometric mean MICs were elevated 14.1- to 25.6-fold. Mueller-Hinton broth containing added NaCl should not be used for testing the susceptibility of staphylococci to aminoglycosides.
Antibacterial activity of Ro 17-2301 and other antimicrobial agents against cefotaxime-resistant aerobic gram-negative bacilli
Authors: Benson C A , Walton F E , Trenholme G M
Published: June 2012

The in vitro activity of Ro 17-2301 was determined and compared with those of aztreonam, ceftazidime, amikacin, and piperacillin against 141 cefotaxime-resistant gram-negative bacilli. Ro 17-2301 was bactericidal, and its activity against the majority of these organisms was equal or superior to those of ceftazidime, aztreonam, and piperacillin. An inoculum effect of Ro 17-2301 and aztreonam for many Pseudomonas aeruginosa and Enterobacter spp. isolates was demonstrated.
Effect of low-dose dopamine on the pharmacokinetics of tobramycin in dogs
Authors: Kirby M G , Dasta J F , Armstrong D K , Tallman R
Published: June 2012

Low-dose dopamine or a placebo was given to six healthy mongrel dogs, each receiving tobramycin at 2.0 mg/kg on consecutive days in a randomized crossover fashion. Dopamine increased the total and renal clearances and elimination rate constant of tobramycin by 12.5, 20, and 25.9%, respectively, suggesting that low-dose dopamine increases the clearance of tobramycin in dogs primarily through renal mechanisms.
Acyclic guanosine analogs as substrates for varicella-zoster virus thymidine kinase
Authors: Karlström A R , Källander C F , Abele G , Larsson A
Published: June 2012

This study was performed to obtain information on the enzymatic background to the antiviral activity of acyclic guanosine analogs. Five acyclic guanosine analogs, the (R)- and (S)-enantiomers of 9-(3,4-dihydroxybutyl)guanine, 9-(4-hydroxybutyl)guanine, 9-[(2-hydroxyethoxy)methyl]guanine, and 9-[[2-hydroxy-1-(hydroxymethyl)ethoxy]methyl]guanine, were compared in enzyme kinetic experiments using purified varicella-zoster virus and human placenta mitochondrial thymidine kinase (TK). All analogs showed competitive patterns of inhibition in the phosphorylation of thymidine by varicella-zoster virus TK, but only low affinities and phosphorylation rates were observed. No affinity for the mitochondrial TK was observed for any of the analogs.
Oral efficacy of WIN 51711 in mice infected with human poliovirus
Authors: McKinlay M A , Steinberg B A
Published: June 2012

WIN 51711, a new broad-spectrum anti-picornavirus agent, prevented the development of paralysis and subsequent death in mice infected intracerebrally with a lethal dose of human poliovirus type 2 (MEF strain). The prophylactic efficacy of intragastrically administered WIN 51711 was dose dependent over the 3.9- to 62.5-mg/kg (twice daily) dose range, with a minimal significantly effective dose of less than 15.6 mg/kg per dose (twice daily) (P less than 0.008). An oral four times a day dosage regimen initiated 48 h postinfection with WIN 51711 doses as low as 12.5 mg/kg was effective in significantly reducing poliovirus-induced paralysis and death compared with a placebo. Viral titers in the brains and spines of mice infected intracerebrally with 200 50% lethal doses of poliovirus were reduced by 3 to 5 log10 PFU/g in the WIN 51711-medicated group compared with placebo-medicated animals. The potent in vitro and in vivo anti-picornavirus activity of WIN 51711 makes it a potentially useful drug for the treatment of enterovirus infections in humans.
Clinical evaluation of teicoplanin for therapy of severe infections caused by gram-positive bacteria
Authors: Glupczynski Y , Lagast H , Van der Auwera P , Thys J P , Crokaert F , Yourassowsky E , Meunier-Carpentier F , Klastersky J , Kains J P , Serruys-Schoutens E
Published: June 2012

Teicoplanin was evaluated in 47 patients with severe infections, including 14 patients with bone infections, 11 patients with soft-tissue infections, 7 patients with endocarditis, 5 patients with pneumonia, 3 patients with septic thrombophlebitis, 3 patients with septicemia of unknown origin, and 4 patients with miscellaneous infections. Overall, bacteremia was documented in 24 patients. The pathogens isolated were 35 strains of Staphylococcus aureus (including 8 methicillin-resistant strains), 4 strains of Staphylococcus epidermidis, 4 strains of Streptococcus faecalis, 2 strains of Streptococcus pneumoniae, 5 strains of other streptococci, and 1 Micrococcus luteus strain. A total of 22 patients (46.8%) were clinically cured, 8 patients (17.0%) improved, 2 patients (4.3%) had relapses after initial improvement, and 15 patients (31.9%) failed to respond. The results were better in nonbacteremic patients (19 of 23 patients [82.6%] were cured or improved) than in patients with bacteremia (12 of 24 patients [50%] were cured or improved). Bacteriological cure occurred in 25 patients (53.2%), and superinfections were documented in 6 patients (12.8%). No major adverse effects were observed. We conclude that teicoplanin is a potentially effective and well-tolerated antimicrobial agent for therapy of nonbacteremic infections caused by gram-positive bacteria.
Effects of selenazofurin and ribavirin and their 5'-triphosphates on replicative functions of influenza A and B viruses
Authors: Wray S K , Smith R H , Gilbert B E , Knight V
Published: June 2012

We studied the effects of selenazofurin alone and in combination with ribavirin on replication of influenza A and B viruses. These drugs showed little cytotoxicity as measured by leucine incorporation into protein in MDCK cells, although they were potent inhibitors of viral replication in the same cells. Selenazofurin inhibited growth of influenza A and B viruses at concentrations (50% inhibitory dose = 25 and 19 microM, respectively) which were similar to those at which growth was inhibited by ribavirin (50% inhibitory dose = 50 and 30 microM, respectively). The inhibition of replication of either influenza A or B virus was additive for any combination of ribavirin and selenazofurin. The effects of the 5'-triphosphate of selenazofurin on two replicative functions associated with the influenza virus RNA-dependent RNA polymerases, primer generation (initiation of transcription) and its subsequent elongation, were measured. Elongation was more sensitive to selenazofurin 5'-triphosphate than was primer generation, and the effects of this drug on these functions were approximately the same as those of ribavirin 5'-triphosphate. The activities of ribavirin triphosphate and selenazofurin triphosphate were additive, and combinations did not potentiate the individual inhibitory effects of these drugs on elongation.
A competitive enzyme-linked immunosorbent assay to quantitate acyclovir and BW B759U in human plasma and urine
Authors: Tadepalli S M , Quinn R P , Averett D R
Published: June 2012

A simple and sensitive enzyme-linked immunosorbent assay for the detection and quantitation of acyclovir in human plasma and urine was developed. Acyclovir immobilized on a solid phase and free acyclovir in the sample solution were allowed to compete for a limited amount of anti-acyclovir monoclonal antibody. The specific antibody bound to the immobilized acyclovir was detected by the use of alkaline phosphatase-conjugated anti-mouse immunoglobulin. The resulting enzyme activity was inversely related to acyclovir concentration in the sample. The Hill plot of standard acyclovir concentrations was linear over a 100-fold concentration range, with a lower detection limit of 0.2 nM and a concentration of soluble ligand displacing 50% of available antibody of approximately 1 nM. The metabolites of acyclovir cross-reacted minimally, and there was no detectable interference by various unrelated compounds tested in the assay. However, BW B759U [9-(2-hydroxy-1-hydroxymethylethoxy)methylguanine], a congener of acyclovir, cross-reacted significantly. As a consequence, the assay was found useful in measuring the concentrations of BW B759U in clinical samples devoid of acyclovir.
Effects of growth of methicillin-resistant and -susceptible Staphylococcus aureus in the presence of beta-lactams on peptidoglycan structure and susceptibility to lytic enzymes
Authors: Qoronfleh M W , Wilkinson B J
Published: June 2012

Growth of methicillin-resistant Staphylococcus aureus DU4916 in the presence of methicillin yielded crude cell walls that showed an increased rate of autolysis and purified cell walls (PCW) and peptidoglycan (PG) that had increased susceptibilities to autolysin extracted with LiCl and to lysozyme. The PG of cells grown in the presence of methicillin had markedly decreased cross-linking and O acetylation. Growth of the methicillin-susceptible strain H in the presence of subinhibitory concentrations of cefoxitin, a specific inhibitor of penicillin-binding protein (PBP) 4, caused a substantial decrease in PG cross-linking and O acetylation and increased susceptibilities of PCW and PG to LiCl-extracted autolysin and to lysozyme. Strain DU4916 cells grown in the presence of methicillin did not show an increased rate of autolysis or an increased susceptibility to vancomycin- or D-cycloserine-induced lysis, even though their PG was hypo-cross-linked. This implies that the potential for increased autolysis is controlled in intact cells and that this regulation may be involved in the methicillin resistance phenomenon. Growth of the methicillin-susceptible strain DU4916S in the presence of methicillin yielded PCW and PG that showed small increases in susceptibilities to LiCl-extracted autolysin and to lysozyme and a small decrease in PG cross-linking. Comparison of the PBPs of a penicillinase-nonproducing derivative of strain DU4916 (DU4916-K7) with those of strain DU4916S in intact cells and isolated membranes revealed that PBPs 1 to 4 had similar high beta-lactam antibiotic affinities in both strains and identified an additional PBP, PBP2(1), with low beta-lactam affinity in the methicillin-resistant strain DU4916-K7. The low degree of cross-linking of PG in strain DU4916 cells grown with methicillin was probably due mainly to inhibition of the secondary cross-linking function of PBP 4.
Prospective randomized comparison of three antibiotic regimens for empirical therapy of suspected bacteremic infection in febrile granulocytopenic patients
Authors: Klastersky J , Glauser M P , Schimpff S C , Zinner S H , Gaya H
Published: June 2012

The standard regimen used by members of the European Organization for Research on Treatment of Cancer Antimicrobial Therapy Cooperative Group for empiric therapy of febrile neutropenic cancer patients has been treatment with ticarcillin plus amikacin. A three-arm prospective randomized controlled trial was performed to determine whether the extended-spectrum antipseudomonal penicillin azlocillin or the extended-spectrum cephalosporin cefotaxime had more or less efficacy than the beta-lactam in the ticarcillin-plus-amikacin regimen. A total of 742 patients from 22 institutions were evaluated. Single gram-negative rod bacteremias accounted for 83 episodes, and it was among these patients that the prognosis was least satisfactory, leading to a more intensive evaluation of this patient group. In these patients the azlocillin-plus-amikacin regimen resulted in a 66% response rate, compared with a 37% response rate for patients who received cefotaxime plus amikacin (P = 0.080) and a 47% response rate for patients who received ticarcillin plus amikacin (P = 0.207). The patients with gram-negative rod bacteremias and persistently profound granulocytopenia had substantially poorer response rates (37%) than the patients with rising granulocyte counts (73%; P = 0.004). A logistic regression analysis indicated that the following factors also affected infection resolution: beta-lactam utilization in the regimen (azlocillin was better than ticarcillin or cefotaxime), resolution of profound granulocytopenia (less than 100 cells per microliter) during therapy, and susceptibility to the beta-lactam antibiotic.
In vitro and in vivo studies of imipenem-cilastatin alone and in combination with gentamicin against Listeria monocytogenes
Authors: Kim K S
Published: June 2012

Imipenem was evaluated for its in vitro and in vivo activities alone and in combination with gentamicin against a clinical isolate of Listeria monocytogenes, and the results were compared with the activities of ampicillin with and without gentamicin. In vitro, the MBC of imipenem was fourfold less than that of ampicillin. Checkerboard determinations of the MBCs exhibited a synergistic response for imipenem-gentamicin but an indifferent response for ampicillin-gentamicin. In vivo studies with experimental bacteremia and meningitis due to L. monocytogenes in newborn rats revealed that both imipenem-cilastatin and ampicillin at a dose of 50 mg/kg produced excellent bactericidal titers in serum. Overall mortality rates were not significantly different among four groups of animals receiving imipenem-cilastatin, imipenem-cilastatin-gentamicin, ampicillin or ampicillin-gentamicin. However, imipenem-cilastatin alone or in combination with gentamicin was significantly less effective than ampicillin-gentamicin, as judged by the rapidity of clearance of bacteria from blood, liver, and spleen. These findings suggest that imipenem-cilastatin and imipenem-cilastatin-gentamicin may not be suitable alternatives for the treatment of listeriosis.
Efficacy of the acyclic guanosine analog buciclovir [(R)-9-(3,4-dihydroxybutyl)guanine] in experimental genital herpes
Authors: Lundgren B , Ericson A C , Berg M , Datema R
Published: June 2012

The efficacy of the anti-herpesvirus drug buciclovir [(R)-9-(3,4-dihydroxybutyl)guanine] was investigated in guinea pigs and mice infected intravaginally with herpes simplex virus type 2. Topical treatment initiated early after infection was efficacious, in contrast to topical treatment delayed 24 h or more. Systemic treatment of infected mice could not prevent the spread of virus to the brain and mortality. Systemically administered buciclovir had an effect in guinea pigs, even after delayed onset of treatment, but this effect required high doses of the drug. Our results suggest that buciclovir has only a limited effect against herpesvirus infections once the virus is present in the nervous systems of infected animals.
In vitro comparison of A-56619, A-56620, amifloxacin, ciprofloxacin, enoxacin, norfloxacin, and ofloxacin against methicillin-resistant Staphylococcus aureus
Authors: Smith S M
Published: June 2012

Seven quinolone antibiotics were tested against 115 isolates of methicillin-resistant Staphylococcus aureus. The MICs for 90% of the strains tested were 0.5 microgram/ml for A-56619, A-56620, ciprofloxacin, and ofloxacin; 2.0 micrograms/ml for amifloxacin and enoxacin; and 4.0 micrograms/ml for norfloxacin. Killing kinetic studies showed a similar killing rate for all seven antibiotics.
Effect of ciprofloxacin on mitogen-stimulated lymphocyte proliferation
Authors: Gollapudi S V , Prabhala R H , Thadepalli H
Published: June 2012

Ciprofloxacin was tested for its inhibitory or stimulatory effects on concanavalin A- and phytohemagglutinin-stimulated proliferation (measured by [3H]thymidine uptake) of human peripheral blood mononuclear cells and murine splenocytes. Ciprofloxacin did not diminish or enhance mononuclear cell proliferation at concentrations of 5 to 125 micrograms/ml. Further, the proliferative response of splenocytes of mice previously treated with ciprofloxacin (40 mg/kg, twice daily for 5 days) was essentially similar to that of untreated controls.
Dissemination of the tetM tetracycline resistance determinant to Ureaplasma urealyticum
Authors: Roberts M C , Kenny G E
Published: June 2012

Ureaplasma urealyticum is an organism considered susceptible to tetracycline. Ten tetracycline-resistant (Tcr) clinical isolates and Tcr serotype 9 were examined. All contained DNA sequences homologous to the streptococcal determinant tetM. They differed from each other on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Southern blots, and immunoblots and appeared to represent different strains.
In vitro activity of BRL 36650, a new penicillin
Authors: Van Landuyt H W , Lambert A , Boelaert J , Gordts B
Published: June 2012

Compared with four beta-lactam antibiotics and amikacin, BRL 36650 and BMY-28142 were the most active against 509 Enterobacteriaceae, including cefotaxime-resistant isolates and resistant laboratory mutants. BRL 36650 was more active than aztreonam, ceftazidime, and BMY-28142 against Acinetobacter spp., Pseudomonas aeruginosa, and other Pseudomonas spp.; all strains were inhibited by 2 micrograms/ml or less.
Comparison of susceptibilities of varicella-zoster virus and herpes simplex viruses to nucleoside analogs
Authors: Machida H
Published: June 2012

The susceptibilities of varicella-zoster virus (VZV) and herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) to 17 nucleoside analogs were compared by a plaque reduction assay with human embryonic lung fibroblast cells. The susceptibility of VZV to certain nucleoside analogs was different from that of HSV-1. Against VZV the 5-halogenovinyl-arabinosyluracils were the most potent of the compounds tested.
Differential effect of impaired renal function on the kinetics of clavulanic acid and amoxicillin
Authors: Horber F F , Frey F J , Descoeudres C , Murray A T , Reubi F C
Published: June 2012

Amoxicillin and clavulanic acid are prescribed as a fixed drug combination. The purpose of the present study was to assess the influence of various degrees of renal insufficiency (glomerular filtration rate [GFR], less than 5 to greater than 75 ml/min per 1.73 m2) on the pharmacokinetics of amoxicillin and clavulanic acid following oral (500 and 125 mg of amoxicillin and clavulanic acid, respectively) and intravenous (1,000 and 200 mg, respectively) dosing. The volume of distribution and the systemic availability were independent of the renal function, while the total body clearance and the renal and the nonrenal clearance of amoxicillin and clavulanic acid decreased with decreasing renal function. The decrease in the total body clearance was more pronounced for amoxicillin than for clavulanic acid. This explains the increase in the ratio of the area under the plasma concentration versus time curve of amoxicillin to that of clavulanic acid with decreasing glomerular filtration rate after oral dosing; for example for a GFR of 75 ml/min, the ratio of amoxicillin to clavulanic acid was 4.9 +/- 1.2; for a GFR of 35 to 75 ml/min, 5.3 +/- 2.4; for a GFR of 10 to 35 ml/min, 11.9 +/- 5.8; for a GFR of 5 to 10 ml/min, 13.4 +/- 9.1; and for patients on hemodialysis, 14.7 +/- 5.3. Dosage recommendations are suggested which prevent undue accumulations of amoxicillin while maintaining adequate concentrations of clavulanic acid.
Avermectin B2 O-methyltransferase activity in "Streptomyces avermitilis" mutants that produce increased amounts of the avermectins
Authors: Schulman M D , Valentino D , Nallin M , Kaplan L
Published: June 2012

The level of activity of avermectin B O-methyltransferase, the enzyme which catalyzes the conversion of avermectin B components to avermectin A components, was analyzed in a series of "Streptomyces avermitilis" mutants selected for increased production of the avermectins. In all of the mutants, increased avermectin production was accompanied by increased avermectin B O-methyltransferase activity. Both the average specific activity and the maximum observed specific activity of avermectin B O-methyltransferase increased in direct proportion to avermectin production. The level of avermectin B O-methyltransferase alone did not determine the extent of conversion of avermectin B components to avermectin A components, since a constant ratio of B components to A components was maintained throughout the fermentation even though avermectin B O-methyltransferase specific activity varied three- to fivefold. These results indicate that avermectin B O-methyltransferase is not rate limiting. The correlation between avermectin B O-methyltransferase specific activity and avermectin production is compatible with the hypothesis that genes coding for successive steps in the same secondary metabolite biosynthetic pathway are coordinately regulated.
Prevention of traveler's diarrhea by the tablet form of bismuth subsalicylate
Authors: Steffen R , DuPont H L , Heusser R , Helminger A , Witassek F , Manhart M D , Schär M
Published: June 2012

In a randomized double-blind study, Swiss adults traveling to tropical countries for 12 to 28 days took a solid formulation of bismuth subsalicylate (1.05 or 2.1 g/day on a twice-daily regimen) or placebo. Efficacy was evaluated in 231 volunteers. Diarrheal incidence was reduced by 41% in persons taking the high dose (P = 0.007) and by 35% in those taking the low dose (P = 0.03) with excellent compliance. No serious adverse reactions occurred, but objectionable taste, constipation, and nausea were seen more frequently with active medication (P = 0.04). Twenty patients provided stool samples: no bacteria were detected in the 8 volunteers who were on active medication, but various bacteria were found in 5 of the 12 patients who had taken placebo (P = 0.04).
Comparative efficacies of single intravenous doses of ceftriaxone and ampicillin for shigellosis in a placebo-controlled trial
Authors: Kabir I , Butler T , Khanam A
Published: June 2012

To evaluate ceftriaxone for the treatment of shigellosis, 94 adult males with acute dysentery were randomly assigned to receive ceftriaxone (1 g), ampicillin (4 g), or saline placebo intravenously in single doses in a double-blind design. Stool cultures were positive for Shigella dysenteriae in 52 patients, S. flexneri in 38 patients, and other species in 4 patients. Both ceftriaxone and ampicillin caused reductions in the mean duration of fever and the means of daily stool frequency 2 to 4 days after therapy versus placebo (P less than 0.05). The ability of ceftriaxone to reduce stool frequency during 6 days after treatment was significant in patients with S. flexneri infections (P less than 0.05), whereas S. dysenteriae infections were relatively refractory to improvement by both antibiotics. Neither drug had a significant effect on overall duration of diarrhea, blood in stool, or tenesmus. Ampicillin reduced the mean duration of positive stool cultures after treatment from 2.6 days in the placebo group to 1.1 days (P less than 0.05), whereas ceftriaxone did not affect the duration of Shigella sp. excretion. These results indicate that single intravenous doses of ceftriaxone and ampicillin caused some clinical improvement in acute shigellosis but only ampicillin exerted a bacteriological effect on Shigella sp. excretion.
Disposition kinetics of cefamandole during continuous ambulatory peritoneal dialysis
Authors: Bliss M , Mayersohn M , Arnold T , Logan J , Michael U F , Jones W
Published: June 2012

Cefamandole disposition kinetics were examined in six male subjects with renal impairment who were undergoing continuous ambulatory peritoneal dialysis. Creatinine clearance values ranged from less than 1 to 11 ml/min. Cefamandole was given as a 1-g intravenous dose infused over 30 min. Cefamandole concentrations were determined in serum, urine, and dialysis fluid by a high-performance liquid chromatographic method. The following average parameter values were obtained (range): half-life, 6.1 h (4.6 to 9.7); systemic clearance, 21.9 ml/min (8.4 to 35.5); renal clearance, 11.5 ml/min (0.03 to 22.3); dialysis clearance, 0.92 ml/min (0.7 to 1.3); nonrenal clearance, 12.2 ml/min (2.9 to 27.0); volume of distribution, 0.18 liter/kg (0.09 to 0.25); steady-state volume of distribution, 0.17 liter/kg (0.09 to 0.24). Approximately 5% of the dose was dialyzed (range, 2.8 to 8.3), indicating that there is no need to supplement a dosing regimen of cefamandole due to loss by dialysis. There was a positive correlation between creatinine clearance and the terminal elimination rate constant of cefamandole (r2 = 0.41) and cefamandole renal clearance (r2 = 0.83).
Effect of imipenem-cilastatin therapy on fecal flora
Authors: Welkon C J , Long S S , Gilligan P H
Published: June 2012

Alteration of fecal flora was prospectively studied in 21 children receiving imipenem-cilastatin therapy under protocol for therapy of infections. Although no profound reduction in facultative or anaerobic flora was observed, qualitative and quantitative increases in organisms which were resistant or less susceptible to imipenem occurred. Of 21 patients, 13 (62%) had increases in counts of Enterococcus spp. of at least 10(3) organisms per g (wet weight) of stool, and 7 (33%) had acquisition of or similar increases in counts of Candida species. No change in susceptibility of isolates to imipenem was demonstrable during therapy. However, the MICs for 50 and 90% of the strains of Enterococcus spp. (2 and 8 micrograms/ml, respectively) were higher than those previously reported.
BRL-36650: in vitro studies and assessment of serum bactericidal activity after single-dose administration in volunteers
Authors: Pascual-Lopez A , Van der Auwera P , Lieppe S , Klastersky J
Published: June 2012

Ten healthy volunteers received 1 g of BRL-36650, a new formamido-penicillin derivative, given by intravenous infusion over 15 min. Levels in serum were measured microbiologically 30, 60, and 120 min after the start of the 15-min infusion and were (mean +/- standard deviation) 102.7 +/- 28.4, 59.7 +/- 11.5, and 9.6 +/- 1.9 mg/liter, respectively. A total of 10 strains each of Escherichia coli, Klebsiella pneumoniae, Serratia spp., and Enterobacter spp. and 14 strains of Pseudomonas aeruginosa were selected according to their susceptibility or resistance to piperacillin for the study of serum bactericidal activity (SBA). The MICs and MBCs of these strains were influenced by the choice of medium. Median SBA against E. coli and K. pneumoniae were greater than or equal to 1:2,048 and 1:512, respectively. The SBA against piperacillin-susceptible Serratia spp. (1:256), Enterobacter spp. (1:128), and P. aeruginosa (1:32) were significantly higher than against piperacillin-resistant strains (1:32, 1:8, and 1:4, respectively). Killing curves confirmed the high bactericidal activities obtained against the majority of strains. In the case of one Enterobacter sp. and one P. aeruginosa isolate with an MBC greater than or equal to 32, the absence of killing was noted.
Lack of relevance of kinetic parameters for exocellular DD-peptidases to cephalosporin MICs
Authors: Boyd D B , Ott J L
Published: June 2012

MICs of a set of cephalosporins against a variety of gram-positive and gram-negative pathogens showed no strong correlations with the rate at which these inhibitors acylate or are deacylated by beta-lactam-sensitive DD-peptidases excreted by Streptomyces sp. strain R61 and Actinomadura sp. strain R39.
Clinical comparative study on the activity of cefamandole in the treatment of serious staphylococcal infections caused by methicillin-susceptible and methicillin-resistant strains
Authors: Frongillo R F , Donati L , Federico G , Martino P , Moroni M , Ortona L , Palumbo M , Pasticci B M , Pizzigallo E , Privitera G
Published: June 2012

Ninety-two microbiologically documented staphylococcal infections were treated with cefamandole in an open comparative study on the clinical efficacy of this cephalosporin in the therapy of infections caused by both methicillin-susceptible and methicillin-resistant Staphylococcus aureus and coagulase-negative Staphylococcus spp. The majority of the episodes (86 of 92) were treated with cefamandole alone, and six were treated with cefamandole in association with other antibiotics. In the evaluable S. aureus infections, 34 of 46 (73.9%) due to methicillin-susceptible strains and 12 of 16 (75%) due to methicillin-resistant strains responded to therapy. In particular, among the patients infected by methicillin-susceptible S. aureus 6 of 9 cases of septicemia, 0 of 2 cases of endocarditis, 2 of 2 cases of pneumonia, 2 of 3 osteoarticular infections, 8 of 12 cases of peritonitis in patients with chronic renal failure in continuous ambulatory peritoneal dialysis (CAPD), 13 of 15 skin-soft tissue infections, and 3 of 3 urinary tract infections responded to therapy. Among those due to methicillin-resistant strains, cure was achieved in 2 of 4 cases of septicemia, 0 of 1 case of endocarditis, 9 of 10 skin-soft tissue infections, and 1 of 1 urinary tract infection. In the evaluable infections caused by coagulase-negative staphylococci, 9 of 11 (81.8%) due to methicillin-susceptible and 15 of 17 (88.2%) due to methicillin-resistant strains responded to therapy. In particular, among patients infected by methicillin-susceptible, coagulase-negative staphylococci, 4 of 4 cases of septicemia, 0 of 1 case of endocarditis, 1 of 1 case of pneumonia, 1 of 1 case of peritonitis in CAPD, 2 of 3 infections of skin-soft tissue, and 1 of 1 urinary tract infection responded to therapy. Among patients infected by methicillin-resistant, coagulase-negative staphylococci were cured 5 of 6 cases os septicemia, 6 of 6 cases of peritonitis (in CAPD), 4 of 4 infections of skin-soft tissue, and 0 of 1 urinary tract infection.
Transfer of amikacin resistance by closely related plasmids in members of the family Enterobacteriaceae isolated in Chile
Authors: Van Nhieu G T , Goldstein F W , Pinto M E , Acar J F , Collatz E
Published: June 2012

During a 9-month period when amikacin was the sole aminoglycoside used clinically in a hospital in Santiago, Chile, resistance to amikacin and other antibiotics was encountered in 42 strains of the family Enterobacteriaceae, including Escherichia coli, Klebsiella pneumoniae, Citrobacter freundii, Enterobacter cloacae, Serratia marcescens, and Serratia liquefaciens. Amikacin resistance was transferable by conjugation and carried by IncM plasmids ranging in size from ca. 48.4 to 58.1 kilobase pairs. The plasmids had ca. 70 to 80% of their structure in common, as judged after digestion with restriction endonucleases. The resistance was mediated by a 6' aminoglycoside acetyltransferase. We conclude that selective pressure has favored the dissemination of a wide-host-range amikacin resistance plasmid and its derivatives.
Ergosterol biosynthesis inhibition by the thiocarbamate antifungal agents tolnaftate and tolciclate
Authors: Ryder N S , Frank I , Dupont M C
Published: June 2012

The thiocarbamate antimycotics tolnaftate and tolciclate blocked sterol biosynthesis in fungal cells and cell extracts, with accumulation of squalene. This point of action was confirmed by the direct inhibition of microsomal squalene epoxidase from Candida albicans. There was no inhibition of other steps in ergosterol biosynthesis. In whole Candida cells, ergosterol biosynthesis inhibition was not complete at drug concentrations up to 100 mg/liter, whereas full inhibition occurred in a cell-free test system. Rat liver cell-free cholesterol biosynthesis was much less sensitive to the drugs. The biochemical action of tolnaftate and tolciclate is thus similar to that of the allylamine antimycotics naftifine and terbinafine.
Comparison of norfloxacin and nalidixic acid for treatment of dysentery caused by Shigella dysenteriae type 1 in adults
Authors: Rogerie F , Ott D , Vandepitte J , Verbist L , Lemmens P , Habiyaremye I
Published: June 2012

A severe epidemic of dysentery began late in 1979 in northeast Zaire and spread to Rwanda, Burundi, and Tanzania. The epidemic strain is a multiply resistant Shigella dysenteriae type 1, which acquired resistance against trimethoprim and more recently against nalidixic acid in the course of the epidemic. A comparative open trial in Rwandan adults with Shiga dysentery involved 18 patients treated with norfloxacin at 400 mg twice daily and 12 patients treated with nalidixic acid at 1 g three times daily for 5 days. All isolates showed in vitro susceptibility to both drugs. Though norfloxacin eliminated Shigella organisms from stools more rapidly than nalidixic acid, its clinical superiority did not reach the level of significance. Norfloxacin is a promising drug and is more effective than nalidixic acid in the treatment of multiresistant shigellosis.
Cefotetan pharmacokinetics in volunteers with various degrees of renal function
Authors: Smith B R , LeFrock J L , Thyrum P T , Doret B A , Yeh C , Onesti G , Schwartz A , Zimmerman J J
Published: June 2012

Twenty-six volunteers with various degrees of renal function were given a single 1-g dose of cefotetan intravenously over 30 min. Concentrations of cefotetan and cefotetan tautomer in plasma and urine were determined by high-performance liquid chromatography. The pharmacokinetic parameters for cefotetan were calculated according to a two-compartment open model. The mean plasma cefotetan concentration at the end of the intravenous infusion did not vary with renal function and ranged between 122 and 126 micrograms/ml. The mean terminal half-life was 4.2 h in normal volunteers and 9.9 h in volunteers with moderate renal impairment. There was a significant linear correlation between the systemic clearance of cefotetan and creatinine clearance. The cumulative amount of cefotetan excreted in the urine over 24 h in normal volunteers was approximately 49% of the dose, but this was reduced in volunteers with moderate renal impairment. The mean urinary cefotetan concentrations generally peaked during the 2- to 4-h interval after dosing. Cefotetan tautomer was sporadically detected in the plasma and urine of approximately 50% of the volunteers. The mean plasma cefotetan tautomer concentrations and mean total cumulative urinary recoveries of cefotetan tautomer were only minimal compared with those for cefotetan. The mean percentage of the dose excreted in the urine as cefotetan tautomer was not significantly affected by the degree of renal impairment. Recommendations for the dosing of cefotetan in renal-impaired patients are given.
Comparative capacity of orally administered amoxicillin and parenterally administered penicillin-streptomycin to protect rabbits against experimentally induced streptococcal endocarditis
Authors: Pujadas R , Escriva E , Jane J , Fernandez F , Fava P , Garau J
Published: June 2012

A single-intramuscular-dose immunization regimen with a penicillin G-streptomycin combination was compared with three oral-dose amoxicillin regimens for the capacity to prevent Streptococcus sanguis infections of experimentally induced valvular heart lesions in rabbits. Challenge doses of 10(4), 10(6), and 10(8) CFU of a strain of S. sanguis equally susceptible to penicillin and amoxicillin were used in this study. Measured by recovery of test organisms from endocardial lesions, the lowest concentration of these inocula was infective for 60% of the recipients; the two higher-concentration inocula were infective for all recipients. The penicillin G-streptomycin combination provided complete protection against infection with inocula of all sizes. A single-oral-dose amoxicillin regimen (50 mg/kg of body weight) prevented endocarditis when rabbits were challenged with 10(4) CFU, but protection diminished with increasing inoculum concentrations. Similar results were achieved when five oral doses of amoxicillin (8.5 mg/kg of body weight) added at 8-h intervals were included in the single-oral-dose regimen. In contrast, when rabbits received two oral doses of amoxicillin (50 mg/kg of body weight) with a 10-h interval between doses, prophylaxis was fully effective with even the highest inoculum concentration.
Inhibition of herpes simplex virus type 1 replication by halothane
Authors: Bedows E , Holland T C , Knight P R
Published: June 2012

Halothane (2-bromo-2-chloro-1,1,1-trifluoroethane) inhibited herpes simplex virus type 1 (HSV-1) replication, although HSV-1 DNA was synthesized at normal levels in Vero cells. Viral capsids and extracellular virions were inhibited, and HSV-1 protein synthesis decreased by 50%, although no specific HSV-1 protein failed to be synthesized. Hyperbaric pressure failed to reverse the halothane-induced inhibition of HSV-1 replication.
Autoradiography of tobramycin uptake by the proximal and distal tubules of normal and endotoxin-treated rats
Authors: Bergeron M G , Bergeron Y , Marois Y
Published: June 2012

Multiple factors may modify the pharmacokinetics of aminoglycosides and increase their nephrotoxic potential. In the present study, the influence of Escherichia coli endotoxin on the renal handling of [3H]tobramycin was investigated. The accumulation of [3H]tobramycin in proximal tubules, distal tubules, and collecting ducts was compared in both normal and endotoxin-injected (0.25 mg/kg) rats. Histological observations were also made. Blood pressure and cardiac frequency were recorded, and renal function was evaluated with labeled inulin and p-aminohippuric acid. Following administration of endotoxin, disturbed intrarenal localization of the drug was noted. Grain counts were affected in both proximal and distal tubules. Increased labeling was observed at all time intervals in the proximal tubules. In the distal tubules of endotoxemic animals we could detect higher amounts of drug at 10 and 60 min in the medulla and at 10 min in the cortex. Not all of the tubules were labeled to the same extent. No histological lesion was noted on light microscopy in animals receiving either normal saline or endotoxin. The dose of endotoxin used resulted in very fine physiological disturbance. Both blood pressure and cardiac frequency were minimally affected by endotoxin. Decreases in glomerular filtration rate and renal plasma flow were observed. However, none of these changes was statistically significant. The present study has shown that low doses of endotoxin alter the renal handling of aminoglycosides in the absence of any major physiological disturbance or histological changes. By increasing the total amount of drug within the kidney, endotoxin might increase the nephrotoxic potential of aminoglycosides.