bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro antibacterial activity of cefpiramide
Authors: Pfaller M A , Niles A C , Murray P R
Published: June 2012

A microbroth dilution method was used to measure the MICs of cefpiramide (SM 1652), cefotaxime, moxalactam, ceftazidime, cefoperazone, ceftriaxone, piperacillin, and mezlocillin against 921 isolates of gram-negative (701) and gram-positive (220) bacteria. The activity of cefpiramide was equivalent to those of piperacillin and mezlocillin against members of the family Enterobacteriaceae and gram-positive isolates, including enterococci. Cefpiramide had equivalent or slightly greater activity against Pseudomonas aeruginosa than the other beta-lactam antibiotics tested.
Ceftazidime in the treatment of pediatric patients with severe urinary tract infections due to Pseudomonas spp
Authors: Rusconi F , Assael B M , Florioli A , Zaffaroni G
Published: June 2012

Fifteen pediatric patients with complicated urinary tract infections due to Pseudomonas spp. were treated for 10 to 18.5 days with ceftazidime administered intramuscularly twice daily. Urine sterilization during therapy was obtained in all patients. Three patients had relapses which were cured with a second course of ceftazidime. Minor liver damage, eosinophilia, and Candida superinfection developed in one patient each.
Comparative in vitro activities of teichomycin and vancomycin alone and in combination with rifampin and aminoglycosides against staphylococci and enterococci
Authors: Tuazon C U , Miller H
Published: June 2012

The activity of teichomycin A2 was compared with that of vancomycin in vitro against clinical isolates of staphylococci and enterococci. Teichomycin A2 was more active than vancomycin active against all isolates tested. Synergistic studies also demonstrated that teichomycin A2 combined with rifampin is more active than vancomycin combined with rifampin against Staphylococcus aureus and Staphylococcus epidermidis isolates. Teichomycin A2, either singly or in combination with an aminoglycoside, was more active against Streptococcus faecalis isolates.
Absorption, distribution, metabolic fate, and elimination of pefloxacin mesylate in mice, rats, dogs, monkeys, and humans
Authors: Montay G , Goueffon Y , Roquet F
Published: June 2012

Pefloxacin mesylate is well absorbed by the oral route. The antimicrobial activity in dog, cynomolgus monkey, and human plasma was essentially due to unchanged drug which respectively accounted for 64, 94, and 84% of the total activity (ratios derived from relative area under the curve [AUC] values). Half-lives ranged from 1.9 h in mice to 8.6 h in humans. Protein binding was weak, about 20% in plasma. Except in brain, concentrations in most of the organs and tissues tested in rats and dogs were higher than the plasma levels. Microbiological activity in urine was mainly due to pefloxacin and norfloxacin, the N-desmethyl metabolite. The norfloxacin/pefloxacin ratios were 0 in mice, ca. 1 in rats and dogs, 1.6 in cynomolgus monkeys, and 2.3 in humans. The principal urinary compounds were unchanged drug in mice, pefloxacin glucuronide and pefloxacin N-oxide in rats and dogs, norfloxacin and pefloxacin in monkeys, and pefloxacin N-oxide and norfloxacin in humans. The urinary recovery of identified metabolites was 29.5% of the dose in mice, 37.8% in rats, 36.3% in dogs, 26.5% in monkeys, and 58.9% in humans. Biliary excretion occurred and was extensive in rats and dogs, mainly as a glucuronide conjugate of the drug. In rat and human bile, the main active compound was unchanged pefloxacin.
Quantitative uptake studies of 131I-labeled (E)-5-(2-iodovinyl)-2'-deoxyuridine in herpes simplex virus-infected cells in vitro
Authors: Gill M J , Samuel J , Wiebe L I , Knaus E E , Tyrrell D L
Published: June 2012

We have synthesized a 131I-radiolabeled antiviral compound (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVdU) and shown that this agent was selectively trapped within rabbit kidney cells, infected in vitro by thymidine kinase-positive (TK+) herpes simplex virus (HSV). The uptake of 131I-labeled IVdU was specific, as it was not concentrated within either HSV (TK-) or mock-infected cells. In certain conditions, over 40% of the radiolabel was selectively trapped within HSV (TK+)-infected cells. This was a 20- to 30-fold increase over the uptake of 131I-labeled IVdU by HSV (TK-) or mock-infected cells. The uptake of 131I-labeled IVdU varied directly with (i) the dose of the virus used to infect the rabbit kidney cells; (ii) the concentration of radiolabeled IVdU added to the system; and (iii) the time of exposure of IVdU to infected cells. The ability of this agent to be trapped within HSV (TK+)-infected cells merits further evaluation in animal models as it has potential as a noninvasive, herpes-specific diagnostic test, in particular for HSV encephalitis.
Effect of the antimycotic drug naftifine on growth of and sterol biosynthesis in Candida albicans
Authors: Ryder N S , Seidl G , Troke P F
Published: June 2012

Naftifine, a new antimycotic drug of the allylamine class, is a potent inhibitor of ergosterol biosynthesis in Candida albicans. Treated cells showed a dose-dependent drop in ergosterol content; the level was reduced by 60% at concentrations of greater than 50 mg/liter, causing total inhibition of growth. This inhibition coincided with a heavy accumulation of the sterol precursor squalene. Radiolabeling experiments showed that the inhibition of sterol synthesis was complete within 10 min of exposure of cells to the compound. Control cells incorporated [14C]acetate into nonsaponifiable lipids composed primarily of ergosterol, whereas naftifine-treated cells accumulated only labeled squalene. When the drug was removed by washing cells thoroughly in 1% Tween 80, the accumulated squalene was further metabolized to ergosterol. A similar pattern of inhibition was observed in sterol biosynthesis from [14C]mevalonate in a cell-free system. At 50 mg/liter, naftifine gave greater than 99% inhibition of sterol biosynthesis both in whole cells and in cell extracts of C. albicans. The primary action of naftifine appears to be the blocking of fungal squalene epoxidation.
Determination of aminoglycosides in rat renal tissue by enzyme immunoassay
Authors: Provoost A P , Van Schalkwijk W P , Adejuyigbe O , Van Leeuwen W B , Wagenvoort J H
Published: June 2012

The enzyme-multiplied immunoassay technique for the determination of gentamicin or amikacin in serum was evaluated for use in rat renal tissue. After the addition of either gentamicin or amikacin to tissue homogenate, the assay of the supernatant showed a reduced recovery, depending on the amount of renal tissue present per milliliter of homogenate. The recovery was independent of the amount of aminoglycoside added. This reduction could be due to either protein binding or interference with the enzyme-multiplied immunoassay technique by substances released from the renal tissue. When the enzyme-multiplied immunoassay technique is used for aminoglycoside assay in renal tissue, care should be taken to minimize the amount of tissue present in the homogenate or to correct for the decreased recovery.
Ceftazidime nephrotoxicity in rats
Authors: Luft F C , Visscher D W , Nierste D M , Blase D K , Walker N A , Aronoff G R
Published: June 2012

The nephrotoxicity of ceftazidime compared with that of cefazolin or cephaloridine and the capacity of ceftazidime to enhance the nephrotoxicity of tobramycin were evaluated in rats. Only cephaloridine and tobramycin given alone altered creatinine clearance or caused significant histological injury. Our data suggest that ceftazidime is no more nephrotoxic than cefazolin and does not enhance the nephrotoxicity of tobramycin.
Susceptibilities of enterococci to twelve antibiotics
Authors: Tofte R W , Solliday J A , Crossley K B
Published: June 2012

The susceptibilities of 347 urine isolates of enterococci (Streptococcus faecalis, 44%; S. faecalis subsp. zymogenes, 37%; S. faecalis subsp. liquefaciens, 19%) to ampicillin, azlocillin, mezlocillin, piperacillin, vancomycin, gentamicin, erythromycin, rosaramicin, rifampin, rifampin plus trimethoprim (1:4), trimethoprim-sulfamethoxazole (1:20), and chloramphenicol were determined by the agar dilution technique. There were no significant differences in susceptibility to individual agents among the subspecies of S. faecalis. Azlocillin and mezlocillin (MIC for 90% of isolates, 0.78 micrograms/ml) and piperacillin, ampicillin, and vancomycin (MIC for 90% of isolates, 1.56 micrograms/ml) were the most active agents and were significantly more potent than the other reference antibiotics tested.
In vitro activity of fludalanine combined with pentizidone compared with those of other agents
Authors: Wise R , Andrews J M
Published: June 2012

The in vitro activity of fludalanine ( MK641 ) combined with pentizidone ( MK642 ) so as to give a fludalanine /D-cycloserine ratio of 1:1 was compared with the activities of ampicillin, ticarcillin, cefuroxime, ceftazidime, and trimethoprim against 452 recent isolates and known beta-lactam- and trimethoprim-resistant strains. In addition, the in vitro activity of fludalanine - pentizidone on four different media, including a defined medium ( DFN -2), was studied. The MIC of fludalanine - pentizidone against 90% of Escherichia coli, Klebsiella spp., Enterobacter spp., Providencia stuartii, Haemophilus influenzae, Neisseria gonorrhoeae, Staphylococcus aureus, and fecal streptococci was 4 micrograms or less per ml on DFN -2, and activity was somewhat reduced on the other media. Proteus spp. and Pseudomonas aeruginosa (90% MIC, less than or equal to 64 micrograms/ml) and Bacteroides spp. (90% MIC, 16 micrograms/ml) were less susceptible. Generally, fludalanine - pentizidone was less active than ceftazidime and comparable in activity to cefuroxime. beta-Lactamase-producing and trimethoprim-resistant strains tended to be susceptible to fludalanine - pentidizone . In the absence of human serum, the MBC of fludalanine - pentizidone was similar to the MIC. In the presence of increasing concentrations of human serum, there tended to be a greater difference between the MIC and MBC.
Azlocillin pharmacokinetics in patients with cystic fibrosis
Authors: Bosso J A , Saxon B A , Herbst J J , Matsen J M
Published: June 2012

The pharmacokinetics of azlocillin were studied in 10 cystic fibrosis patients, ranging in age from 11 to 28 years. The patients received a 9- to 23-day course of 350 mg of azlocillin per kg in four or six divided daily doses in combination with am aminoglycoside. Blood and urine samples were collected at specified times after the last dose of the course of azlocillin therapy and then assayed for azlocillin content. Pharmacokinetic parameters were determined by noncompartmental analysis. Mean values for serum half-life (1.74 h), disposition constant (0.41 h-1), total body clearance (123 ml/kg per h), and renal clearance (58 ml/kg per h) were determined. All patients exhibited improvement with respect to clinical and laboratory parameters and displayed no adverse reactions. The pharmacokinetic analysis offers further evidence of the dose-dependent nature of azlocillin elimination, but elimination did not appear to be altered in cystic fibrosis patients.
Deletions in Klebsiella pneumoniae R plasmids induced by growth in the presence of acridine orange at high temperature
Authors: Zorzópulos J , Trevisán A R , Denoya C D
Published: June 2012

The generation in vivo of plasmids deleted at specific sites in strains of Klebsiella pneumoniae containing R plasmids, by treatment with high concentrations of acridine orange (1.2 mg/ml) at 42 degrees C are reported. These deletions seem to be site specific because loss of specific restriction fragments after digestion with restriction enzymes was demonstrated.
Probenecid: antibacterial action against Neisseria gonorrhoeae and interaction with benzylpenicillin
Authors: Catlin B W
Published: June 2012

Neisseria gonorrhoeae strains were used in an investigation of the antibacterial action of probenecid and its interaction with benzylpenicillin. The growth of 112 routine isolates was inhibited by probenecid at concentrations of 100 to 500 micrograms/ml incorporated in agar. Additive or synergistic effects of benzylpenicillin-probenecid combinations were graphically illustrated in gradient plates. In agar dilution tests with a resistant gonococcal strain, the MICs of benzylpenicillin alone and probenecid alone were 0.8 and 500 micrograms/ml, respectively; in contrast, the MICs of combinations of benzylpenicillin and probenecid were 0.45 and 75 micrograms/ml and 0.3 and 150 micrograms/ml, respectively. High concentrations of probenecid in broth were bactericidal. Probenecid alone at 50 to 100 micrograms/ml had little antibacterial effect, but in combination with an appropriate concentration of benzylpenicillin, it produced reductions of CFU in 6 h that were 100 to 300 times that produced by benzylpenicillin alone. Thus, in addition to its well-known pharmacological effects, probenecid potentiates the in vitro action of benzylpenicillin for gonococci. I suggest that synergism contributes to the beneficial effect of the benzylpenicillin-probenecid regimen for the treatment of gonorrhea. Furthermore, synergism may explain the reduction in the ratio of partially benzylpenicillin-resistant N. gonorrhoeae strains to benzylpenicillin-susceptible strains that occurred in the United States between 1972 and 1978.
Mezlocillin and ticarcillin alone and combined with gentamicin in the treatment of experimental Enterobacter aerogenes endocarditis
Authors: Levison M E , Kobasa W D
Published: June 2012

The efficacies of mezlocillin and ticarcillin, each alone and in combination with gentamicin, in the therapy of experimental left-sided Enterobacter aerogenes endocarditis in rabbits were compared. Each beta-lactam was administered intramuscularly at a dose of 180 mg/kg every 6 h either alone or with gentamicin (1.7 mg/kg intramuscularly every 8 h). Bacterial populations at the start of therapy (7 days after initiation of infection) were 9 to 10 log10 CFU/g of vegetation. Ticarcillin produced concentrations in serum that were twice those produced by mezlocillin, but the therapeutic ratios of mezlocillin and ticarcillin (ratio of peak level in serum to MBC) were the same. All of the therapeutic regimens given for either 5 or 10 days were effective in reducing vegetation counts when compared with the untreated controls (P less than 0.01 for all comparisons), except mezlocillin alone and ticarcillin alone, which caused insignificant reductions in counts after 5 days of therapy (P greater than 0.05). After 10 days of therapy, the only regimen that was significantly different from another was that of mezlocillin plus gentamicin, which was significantly better than that of ticarcillin alone (P less than 0.01). These studies document that mezlocillin and ticarcillin were both effective in reducing the numbers of E. aerogenes CFU in vegetations in rabbits with experimental endocarditis when the drugs were given over a prolonged course. More rapid and extensive reduction in vegetation counts was achieved with combinations of an aminoglycoside plus mezlocillin or ticarcillin. Mortality was significantly less among rabbits treated with mezlocillin plus gentamicin.
Antibacterial activity of coumermycin alone and in combination with other antibiotics
Authors: Neu H C , Chin N X , Labthavikul P
Published: June 2012

Coumermycin has been shown to inhibit Staphylococcus aureus and Staphylococcus epidermidis strains that are susceptible and those that are resistant to methicillin at concentrations less than or equal to 0.05 micrograms/ml. Listeria monocytogenes and Corynebacterium spp. resistant to cephalosporins were inhibited by less than or equal to 1.6 micrograms of coumermycin ml, and streptococcal species, with the exception of Streptococcus faecalis, were inhibited by 0.1 micrograms/ml. Cross-resistance with beta-lactams or aminoglycosides was not found. Coumermycin acted synergistically with ofloxacin, norfloxacin, and enoxacin against S. aureus but did not show synergy when combined with nafcillin, vancomycin, or rifampin. Coumermycin did not inhibit members of the family Enterobacteriaceae or Pseudomonas aeruginosa.
Antibiotic action on phagocytosed bacteria measured by a new method for determining viable bacteria
Authors: Vosbeck K , James P R , Zimmermann W
Published: June 2012

Antibiotics such as rifampin that act on phagocytosed bacteria have clinical advantages. The investigation of such intraphagocytic activity of antibiotics is, however, hampered by the time-consuming and cumbersome procedures necessary for enumerating viable bacteria. We have developed a semiautomatic biophotometric method for this purpose that permits the processing of relatively large numbers of samples. Using this method with Staphyloccus aureus Wood 46 as a test organism, we studied the dose dependence of the activities of a number of antibiotics against intraphagocytic bacteria. We could confirm the very good intracellular activity of rifampin. Its activity at low concentrations was slightly better against intracellular than against extracellular bacteria. In contrast, clindamycin and erythromycin, both of which have been reported to accumulate within phagocytes, did not exhibit a correspondingly enhanced intracellular activity, erythromycin being active intracellularly only at high concentrations. Clindamycin and vancomycin were effective against intracellular organisms, but only at relatively high concentrations owing to their low bactericidal activity against S. aureus Wood 46. Penicillin G, ampicillin, gentamicin, and streptomycin exhibited no useful intracellular activity. These results demonstrate that radioactive accumulation studies of antibacterial agents are not sufficient to show intracellular activity. Intracellular activity must be demonstrated in a functional test, preferably with graded concentrations of the test substance.
Distribution of ceftazidime in ascitic fluid
Authors: Benoni G , Arosio E , Raimondi M G , Apolloni E , Passarella E , Lechi A , Velo G P
Published: June 2012

The pharmacokinetics of ceftazidime were investigated in eight normal subjects and eight patients with ascites after intravenous administration of 1 g of the drug. Samples of blood and ascitic fluid were collected for 6 h after dosage, and urine samples were collected for 24 h. Pharmacokinetic data were calculated by using a one-compartment model. The apparent volume of distribution and half-life of elimination (t1/2 beta) in patients with ascites were approximately three times those in normal subjects. In contrast, renal clearance was greater in the normal subjects. With respect to ascites, the mean area under the concentration-time curve was 95.3 +/- 38.3 micrograms X h/ml. The mean ratio of the area under the concentration-time curve for ascitic fluid to that for plasma was 69.9% (+/- 38.2). These data show that ceftazidime rapidly diffuses into the peritoneal space, in which concentrations greater than 10 micrograms/ml were present for at least 6 h.
Identification of an envelope mutation (env-10) resulting in increased antibiotic susceptibility and pyocin resistance in a clinical isolate of Neisseria gonorrhoeae
Authors: Shafer W M , Guymon L F , Lind I , Sparling P F
Published: June 2012

A mutation (env-10) conferring increased susceptibility to drugs, dyes, and detergents was detected in a clinical isolate of Neisseria gonorrhoeae. In certain strains, env-10 also affected susceptibility to pyocins. This mutation was phenotypically similar to but genotypically distinct from previously described env mutations.
Improved procedure for extracting aminoglycosides from renal cortical tissue
Authors: Giuliano R A , Verpooten G A , Pollet D E , Verbist L , Scharpé S L , De Broe M E
Published: June 2012

An efficient and reproducible procedure was developed for extracting aminoglycosides from renal cortical tissue. It involves a double homogenization and two rinsings with trichloroacetic acid. A higher recovery is obtained compared with that of other previously reported methods.
Penetration of ceftazidime into the cerebrospinal fluid of patients with and without evidence of meningeal inflammation
Authors: Fong I W , Tomkins K B
Published: June 2012

The concentrations of ceftazidime in the serum and cerebrospinal fluid of patients with and without meningitis were measured at various times after a 2- or 3-g dose. At similar concentrations in serum, ceftazidime concentrations in cerebrospinal fluid at a given time were substantially lower in patients without meningitis (mean, 0.8 micrograms/ml) than in those with meningitis (mean, 22.6 micrograms/ml).
Intranasal interferon-alpha 2 for prevention of natural rhinovirus colds
Authors: Farr B M , Gwaltney J M , Adams K F , Hayden F G
Published: June 2012

The prophylactic activity of intranasal human interferon-alpha 2 (HuIFN-alpha 2) against natural rhinovirus colds was determined in a randomized, double-blind, placebo-controlled trial. A total of 304 working adults self-administered sprays of HuIFN-alpha 2 (10(7) IU/day) or a placebo once daily. During 22 days of treatment, 13 (8.5%) placebo recipients but no HuIFN-alpha 2 recipients had respiratory illnesses documented secondary to rhinovirus infection (P = 0.0002). The occurrence of illness with symptoms of tracheobronchitis was lower in HuIFN-alpha 2 recipients (one eposide) than in placebo recipients (eight episodes, P = 0.04). In contrast, the frequency of nasal symptoms and the overall rate of respiratory illness were significantly higher in HuIFN-alpha 2 recipients during weeks 2 and 3 of treatment. Symptoms (obstruction, discomfort, blood-tinged nasal mucus) or signs (punctate bleeding sites, erosions, superficial ulcerations) of nasal irritation occurred in 40 HuIFN-alpha 2 recipients during week 3 (P less than 0.0001 versus placebo recipients). Although the results of the current study were partially confounded by the nasal side effects of prolonged administration, they showed that intranasal HuIFN-alpha 2 was efficacious in preventing rhinovirus colds under natural conditions.
Compounds which increase the permeability of the Pseudomonas aeruginosa outer membrane
Authors: Hancock R E , Wong P G
Published: June 2012

Hydrolysis of the chromogenic beta-lactam nitrocefin by periplasmic beta-lactamase in intact Pseudomonas aeruginosa cells was used to assess the influence of various compounds on the permeability of the P. aeruginosa outer membrane. In addition to the five previously described outer membrane-active compounds EDTA, polymyxin B, gentamicin, poly-L-lysine, and Tris, seven other compounds were shown to increase outer membrane permeability to nitrocefin by 14- to 63-fold. These other compounds included poly-L-ornithine, neomycin, cetyltrimethylammonium bromide, nitrilotriacetate, L-ascorbate, and acetylsalicylate. In each case, Mg2+ ions antagonized, to different extents, the enhancement of outer membrane permeability. The same compounds increased the permeability of the outer membrane to the protein lysozyme and to the hydrophobic fluorescent probe 1-N-phenylnaphthylamine, although L-ascorbate and acetylsalicylate showed only very weak enhancement of uptake in these assays. In this report, we discuss the possibility that these compounds act at a common outer membrane site at which divalent cations noncovalently cross-bridge adjacent lipopolysaccharide molecules.
In vitro interactions between rifampin and ampicillin or chloramphenicol against Haemophilus influenzae
Authors: Jadavji T , Prober C G , Cheung R
Published: June 2012

Twenty clinical isolates of Haemophilus influenzae type b were used to determine the in vitro interactions of rifampin with ampicillin or chloramphenicol. Potential interactions of the drugs were evaluated by calculating the fractional inhibitory concentration index and fractional bactericidal concentration index for each strain after treatments with the drugs alone and in combination. There was no evidence of synergy or antagonisms between ampicillin and rifampin or between chloramphenicol and rifampin. With ampicillin-susceptible H. influenzae type b strains, an additive effect was observed with seven strains, and an indifferent effect was observed with three strains. Similarly, with chloramphenicol-susceptible H. influenzae type b strains, an additive effect was observed with eight strains, and an indifferent effect was observed with two strains.
Influence of inoculum size on comparative susceptibilities of penicillinase-positive and -negative Neisseria gonorrhoeae to 31 antimicrobial agents
Authors: Hall W H , Opfer B J
Published: June 2012

The effects of two inoculum sizes (10(4) and 10(6) CFU) on the MICs of 20 beta-lactam antibiotics, 4 aminoglycosides, and 7 other antimicrobial agents were compared for 102 unselected strains of Neisseria gonorrhoeae (26 penicillinase positive and 76 penicillinase negative), with three replicates for each test. The method was agar plate dilution on Mueller-Hinton agar supplemented with 1% hemoglobin and 1% IsoVitaleX. For penicillinase-positive strains, a large inoculum (10(6) CFU) increased the MIC greater than or equal to 16-fold for benzylpenicillin, piperacillin, azlocillin, and mezlocillin and increased the MIC greater than or equal to 8-fold for ampicillin, cefoperazone, ceftazidime, cefonicid, and cefamandole. The inoculum size had little or no influence on MICs of any antimicrobial agent for penicillinase-negative strains. For penicillinase-positive strains, the most active antibiotics (MIC, less than or equal to 0.001 microgram/ml) were the new cephalosporins: cefotaxime, ceftazidime, ceftizoxime, ceftriaxone, and cefmenoxime. For penicillinase-negative strains, the most active antibiotics were piperacillin, ceftriaxone, ceftizoxime, and cefmenoxime (MIC, less than or equal to 0.001 microgram/ml), closely followed by ceftazidime, moxalactam, azlocillin, mezlocillin, and cefuroxime.
Disparity between timed-kill and checkerboard methods for determination of in vitro bactericidal interactions of vancomycin plus rifampin versus methicillin-susceptible and -resistant Staphylococcus aureus
Authors: Bayer A S , Morrison J O
Published: June 2012

The role of rifampin as an adjunctive agent to vancomycin in the therapy of serious systemic staphylococcal infections remains controversial. Several in vitro studies utilizing differing methodologies to define the bactericidal interactions of vancomycin plus rifampin versus Staphylococcus aureus have yielded markedly disparate results. The in vitro bactericidal synergistic activities of vancomycin plus rifampin were examined versus 48 clinical isolates of S. aureus, both methicillin susceptible and resistant. Each strain was tested simultaneously in timed-kill curve and checkerboard systems. By timed-kill curve, vancomycin plus rifampin usually had either an indifferent (67%) or synergistic (19 to 29%) effect, with a frequency dependent on sampling times; bactericidal antagonism was infrequently noted after 48 h of incubation (4%). Indifference was seen as a prevention of rifampin resistance by vancomycin. Synergy was more commonly noted at 48 than at 24 h of incubation. The bactericidal interaction results were similar for both methicillin-susceptible and -resistant strains. In contrast to the killing curve data, the checkerboard technique uniformly demonstrated bactericidal antagonism of vancomycin plus rifampin against all 48 staphylococci. We conclude that the nature of the in vitro bactericidal interactions of vancomycin plus rifampin against S. aureus is difficult to establish in vitro. This fact relates to the markedly disparate findings, which depended on both the synergy technique utilized and the test system conditions employed. In vivo studies are required to delineate the bactericidal interaction potentials of vancomycin plus rifampin versus S. aureus.
Correlation of in vitro activities of cephalothin and ceftazidime with their efficacies in the treatment of Staphylococcus aureus endocarditis in rabbits
Authors: Baker R L , Fass R J
Published: June 2012

Rabbits with Staphylococcus aureus endocarditis were treated with cephalothin or ceftazidime to determine whether differences in in vitro activity would result in differences in in vivo efficacy. Antibiotics were administered in doses equivalent to maximum recommended human doses, and results of laboratory tests to predict antimicrobial efficacy were determined during treatment. Cephalothin and ceftazidime MICs for the challenge strain were 0.5 and 8 micrograms/ml, respectively. MBCs were 32 and greater than 128 micrograms/ml, respectively. With peak sera, laboratory results (means) for cephalothin and ceftazidime were as follows: ratios of concentration in serum to MIC, 300 and 16; ratios of concentration in serum to MBC, 4.8 and less than 1; bacteriostatic antibacterial activity titers in serum, 1:256 and 1:16; and bactericidal antibacterial activity titers in serum, 1:16 and 1:4, respectively. Trough sera contained little or no measurable antibiotic and had no antibacterial activity. Both cephalothin and ceftazidime were efficacious in the treatment of infected rabbits. There were no statistically significant differences in efficacy as defined by survival, eradication of bacteremia, or sterilization of cardiac vegetations. Results of laboratory tests which quantitated antimicrobial activity did not correlate with efficacy, either independent of antibiotic or adjusted for antibiotic. Despite their lesser in vitro activities, the new cephalosporins may be equivalent to the older cephalosporins for treating staphylococcal infections in humans, when administered in maximum recommended doses.
Evaluation of aztreonam in difficult-to-treat infections with prolonged posttreatment follow-up
Authors: Giamarellou H , Galanakis N , Douzinas E , Petrikkos G , El Messidi M , Papoulias G , Daikos G K
Published: June 2012

Aztreonam at doses of 1 or 2 g given intramuscularly or intravenously every 8 h for 7 to 42 days was given to 55 patients, most of them suffering from difficult-to-treat infections either because the isolated pathogens were multiresistant or because of the location of the infection. Infections included: urinary tract (23 cases), deep soft tissue phlegmon (12 cases), chronic osteomyelitis in exacerbation (7 cases), abscesses (7 cases), pneumonia (4 cases), and external otitis (2 cases). In culture specimens, Pseudomonas aeruginosa (24 isolates) and various Enterobacteriaceae species (37 isolates) were isolated with MICs ranging from 0.25 to 16 micrograms/ml. Clinically, at the completion of treatment and after a 6-week posttreatment follow-up, 45 (81.6%) patients were cured, 4 (7.2%) improved, 3 (5.6%) relapsed, and 3 (5.6%) failed to respond to therapy. Bacteriologically, at the end of treatment, the pathogen was eradicated in 50 patients (91%) and persisted in 5 (9%). After a 6-week follow-up, cultures remained sterile in 33 patients (60.0%), 16 (29.1%) relapsed, in 6 (10.9%) bacteria persisted, and superinfection was reported in 4 (7.3%) patients. No appreciable adverse effects or toxicity was observed. From the reported results, it is concluded that aztreonam is a valuable addition to the field of antimicrobial chemotherapy that can be used effectively and safely in the treatment of a variety of gram-negative infections.
Imipenem antagonism of the in vitro activity of piperacillin against Pseudomonas aeruginosa
Authors: Bertram M A , Young L S
Published: June 2012

The MICs of imipenem and piperacillin, alone and in combination, against Pseudomonas aeruginosa were determined in a checkerboard titration microdilution assay. A dramatic, one-way antagonism of imipenem for piperacillin was demonstrated in 28 of the 35 strains examined; antagonism was associated with the induction of a beta-lactamase.
Piperacillin plus vancomycin in the therapy of febrile episodes in cancer patients
Authors: Jadeja L , Bolivar R , Fainstein V , Keating M , McCredie K , Hay M , Bodey G P
Published: June 2012

Piperacillin and vancomycin were used as initial empirical therapy for 211 febrile episodes in cancer patients. The response rate in 95 episodes of documented infection was 72%. The response of bacteremias, soft tissue infections, and pneumonias was 78, 71, and 38%, respectively. The response in infections caused by gram-negative organisms was 73%. Only 6 of 10 Pseudomonas aeruginosa infections responded to therapy, although the organisms were sensitive in vitro to piperacillin. Of 14 infections caused by gram-positive organisms, 12 responded to this combination. No major side effects were observed with this regimen. Although the overall response rate with this antibiotic combination was comparable with other regimens used for neutropenic patients, superior results might be obtained by combining piperacillin with an extended-spectrum cephalosporin or an aminoglycoside.
Use of lipids to potentiate the antibacterial activity of aminoglycosides
Authors: Gilbertson J R , Langkamp H H , Connamacher R , Platt D
Published: June 2012

Linolenyl alcohol has been shown to inhibit the in vitro growth of several species of gram-positive bacteria. Since the double bonds in linolenyl alcohol could undergo autooxidation, the antimicrobial activities of saturated primary alcohols of similar molecular sizes against Streptococcus mutans BHT were evaluated. Tridecan-1-ol was identified as the most active compound, eliciting a bacteriostatic effect at concentrations at which growth occurred in the presence of other saturated alcohols or linolenyl alcohol. Evidence is also presented that the combined use of tridecan-1-ol and gentamicin sulfate produces a synergistic effect that is bactericidal to S. mutans BHT. A similar bactericidal response was observed when tridecan-1-ol was combined with other aminoglycosides or tested alone against other strains of S. mutans.
Quantitative extraction of amphotericin B from serum and its determination by high-pressure liquid chromatography
Authors: Bach P R
Published: June 2012

Therapeutic concentrations of amphotericin B in serum were measured by reversed-phase liquid chromatography with detection at 386 nm. Complete recovery of the drug and the internal standard from a 1-ml serum sample was achieved by pretreating the sample with guanidine hydrochloride and extracting it with a disposable reversed-phase phenyl extraction column. The method was sensitive to 0.005 micrograms of amphotericin B per ml and linear to at least 5 micrograms/ml. Coefficients of variation were 4.8% within-run and 6.3% between-run.
Cefmenoxime pharmacokinetics in patients with renal insufficiency
Authors: Polk R E , Sica D A , Kerkering T M , Kline B J , Patterson P M , Baggett J W
Published: June 2012

The pharmacokinetics of cefmenoxime were determined after a 30-min intravenous infusion of 15 mg/kg of total body weight to 33 adult subjects with normal renal function (CLCR, greater than 80 ml/min per 1.73 m2, group I), mild renal insufficiency (CLCR, 40 to 79 ml/min per 1.73 m2, group II), moderate renal insufficiency (CLCR, 10 to 39 ml/min per 1.73 m2, group III), or severe renal impairment, (CLCR, less than 10 ml/min per 1.73 m2, group IV) or to patients between hemodialysis (CLCR, less than 10 ml/min per 1.73 m2, group V). Concentrations of cefmenoxime in serum and urine were determined by high-pressure liquid chromatography, and serum concentrations were fit to a two-compartment model. There was no significant relationship between creatinine clearance and either peak serum concentrations or volume of distribution at steady state. Patients in group I excreted 81% of the dose into the urine within 24 h; recovery decreased with worsening renal function. The mean terminal half-lives in groups I to V were 1.06, 1.50, 3.55, 4.60, and 11.4 h, respectively. There were good linear relationships between creatinine clearance, and the elimination rate and total body clearance of cefmenoxime. Dosage recommendations for subjects with renal insufficiency are proposed.
Treatment of primary acute genital herpes in guinea pigs by intraperitoneal administration of fluoropyrimidines
Authors: Mayo D R , Hsiung G D
Published: June 2012

FIAC [1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodocytosine], FIAU [1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-iodouracil], and FMAU [1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)-5-methyluracil] were evaluated for their efficacies in the treatment of genital infections with herpes simplex virus type 2 in guinea pigs. Intraperitoneal administration of these drugs in daily doses of 100 mg/kg of body weight initiated 24 h after virus inoculation and repeated 2 successive days thereafter inhibited development of genital lesions and reduced shedding of virus without evoking untoward reactions. In a comparative study with this 3-day dosage schedule, the efficacy of daily doses of 50 mg of FMAU per kg was greater than that of the same doses of FIAC and FIAU, in that order; all these were more effective than daily doses of 50, 100, or 200 mg of acyclovir or of 500 mg of phosphonoformic acid per kg. These differences in efficacy were enhanced when treatment was delayed for 2 to 3 days after inoculation.
Comparison of the activities of penicillin G and new beta-lactam antibiotics against clinical isolates of Bacteroides species
Authors: Aldridge K E , Sanders C V , Janney A , Faro S , Marier R L
Published: June 2012

MICs were determined for 218 clinical isolates of Bacteroides by a broth microdilution method. Imipenem was the most active antibiotic tested. Azlocillin, mezlocillin, and cefoxitin had comparable activities, with resistance among members of the B. fragilis group and B. capillosus. Ceftizoxime was the most active cephalosporin tested. Members of the B. fragilis group showed high levels of resistance to cefotetan and ceftazidime. Resistance to penicillin G varied from 0 to 14%.
Inhibition of human cytomegalovirus replication by 9-(1,3-dihydroxy-2-propoxymethyl)guanine alone and in combination with human interferons
Authors: Rasmussen L , Chen P T , Mullenax J G , Merigan T C
Published: June 2012

The inhibitory action of 9-(1,3-dihydroxy-2-propoxymethyl)guanine on the replication of human cytomegalovirus was studied. Three laboratory strains (AD-169, Towne, and Davis) and three early passage (less than 10) clinical isolates were all inhibited in yield inhibition assays. In cultures infected with AD-169, virus yields could be inhibited if the drug was added as late as 3 days after the replication cycle had begun. The effects of the drug were fully reversible during the first 4 days of the viral replication cycle. Viral infectivity and viral DNA synthesis were reduced more than viral protein synthesis. Synergistic antiviral effects were observed with beta-cysteine, and to a lesser extent, with beta-serine recombinant interferons, but only over a narrow range of dose combinations.
Synergistic antiviral effects of ribavirin and the C-nucleoside analogs tiazofurin and selenazofurin against togaviruses, bunyaviruses, and arenaviruses
Authors: Huggins J W , Robins R K , Canonico P G
Published: June 2012

Binary combinations of the N-nucleoside ribavirin (1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide) and the C-nucleoside analog selenazofurin (2-beta-D-ribofuranosylselenazole-4-carboxamide) or tiazofurin (2-beta-D-ribofuranosylthiazole-4-carboxamide) were tested in vitro for activity against Venezuelan equine encephalomyelitis, Japanese encephalitis, yellow fever, Rift Valley fever, Korean hemorrhagic fever, and Pichinde viruses. The 50% effective dose for each compound alone or in a series of combinations was determined with a plaque reduction assay. Combinations of ribavirin and selenazofurin were synergistic against Venezuelan equine encephalomyelitis, Japanese encephalitis, yellow fever, and Pichinde viruses, with fractional inhibitory concentrations of 0.1, 0.2, 0.4, 0.4, respectively, but showed additive effects against Korean hemorrhagic fever and Rift Valley fever viruses. Combinations of ribavirin and tiazofurin were synergistic against yellow fever and Japanese encephalitis (fractional inhibitory concentrations, 0.41 and 0.48, respectively) but showed additive effects against Korean hemorrhagic fever virus. Combinations of selenazofurin and tiazofurin had additive effects against Japanese encephalitis, yellow fever, and Korean hemorrhagic fever viruses. The effect of combinations on cell toxicity was additive, both in monolayers of nondividing cells incubated under agar for the same period as the plaque assay and for rapidly dividing cells given short-term exposure (4 h), followed by determination of the proportion of surviving cells with a colony forming assay.
Regrowth of aminoglycoside-resistant variants and its possible implication for determination of MICs
Authors: Sörén L , Nilsson L
Published: June 2012

Regrowth of aminoglycoside-resistant variants was seen when large inocula of two strains of Escherichia coli were incubated with gentamicin in concentrations well above their MICs (0.5 micrograms/ml). The extent of the selection of resistant variants was proportional to the concentration of gentamicin during incubation; after incubation with gentamicin (greater than or equal to 2 micrograms/ml for 24 h), all bacteria were resistant to at least 8 micrograms/ml. Bacteria resistant to these concentrations always formed small colonies, whereas variants resistant to lower concentrations (1 to 2 micrograms/ml) could form both small and normal colonies. The regrowth of resistant variants could be monitored by luciferase assay of intracellular ATP in cultures incubated with gentamicin (less than or equal to 2 micrograms/ml). In cultures incubated with higher concentrations, regrowth did occur, although this did not result in viability (CFU per milliliter) or ATP levels above those of the initial inocula. The implications of this regrowth for MIC determinations in broth and the possible clinical revelance of the resistant variants are discussed.
Correlation between cytochrome aa3 concentrations and streptomycin accumulation in Bacillus subtilis
Authors: McEnroe A S , Taber H W
Published: June 2012

Accumulation of aminoglycosides by Bacillus subtilis appears to require specific components of the electron transport chain. These components include cytochromes and the lipophilic quinone vitamin K2. The present study concerns the importance of cytochrome aa3, a terminal oxidase, in the uptake of streptomycin. Growth conditions have been established such that the concentration of cytochrome aa3 can be modified over a wide range; on defined minimal salts agar, the wild-type strain (RB1) and an strC mutant (RB95) synthesized cytochrome aa3 only when adequate amounts of Casamino Acids (Difco Laboratories, Detroit, Mich.) were present. A positive correlation between cytochrome aa3 levels and streptomycin accumulation was observed. The same correlation was seen when cytochrome aa3 was measured in relation to growth susceptibility. These correlations suggest that cytochrome aa3 is necessary for accumulation of streptomycin by B. subtilis.
Effect of aztreonam in combination with azlocillin or piperacillin on Pseudomonas aeruginosa
Authors: Wu D H , Baltch A L , Smith R P , Conley P E
Published: June 2012

Aztreonam, a synthetic monobactam antimicrobial agent specifically active against aerobic, gram-negative microorganisms, was studied in combination with the extended-spectrum penicillins azlocillin and piperacillin against 46 strains of Pseudomonas aeruginosa. Of these strains, 4.3% were synergistically inhibited, and 19.7% showed evidence for an additive effect of the antibiotics. All other strains showed indifference. The addition of cefoxitin to these combinations increased the MICs of azlocillin and piperacillin by two to three tubes, whereas zero- to one-tube increases were noted for aztreonam MICs. Attempts to block cefoxitin-induced beta-lactamase production by using clindamycin were unsuccessful even at high clindamycin concentrations.
Pharmacokinetics and metabolism of rosaramicin in humans
Authors: Lin C C , Chung M , Gural R , Schuessler D , Kim H K , Radwanski E , Marco A , DiGiore C , Symchowicz S
Published: June 2012

The pharmacokinetics of rosaramicin was studied in subjects receiving 500 mg of the drug (i) by 1-h intravenous infusion, (ii) in solution orally, or (iii) as tablets orally. After intravenous administration, the rosaramicin levels in serum declined rapidly with t1/2S of 0.27 h for the distribution phase and 3.28 h for the elimination phase. The apparent volume of distribution was 3.78 liter/kg, and the total body clearance was 13.41 ml/min per kg, indicating extensive tissue distribution or metabolism or both. Similar pharmacokinetic data were obtained after oral administration of the drug in solution or tablets and after intravenous dosing. The absolute bioavailability of the drug administered orally, in either tablets or solution, was 32 to 39%. The metabolism and excretion of [14C]rosaramicin administered orally were also evaluated in volunteers. The serum area under the curve (infinity) of unchanged rosaramicin was 19% of that of total radioactivity, indicating extensive metabolism of the drug. About 7.0% of the radioactivity was recovered in the urine, and 86.7% was recovered in the feces. Only a small amount of unchanged rosaramicin was present in the urine (7 to 9% of urinary radioactivity), but none was present in the feces. The major metabolite, 20-bis-ureidorosaramicin, represented 17 to 38% of the radioactivity in the urine and 26 to 29% of the radioactivity in the feces.
Susceptibilities of Mycobacterium fortuitum biovariant fortuitum and the unnamed third biovariant complex to heavy-metal salts
Authors: Wallace R J , Steele L C , Forrester G D , Swenson J M , Hull S I
Published: June 2012

Fifty-three clinical isolates of Mycobacterium fortuitum were tested for susceptibility to heavy-metal salts and antimicrobial agents. The isolates exhibited a bimodal distribution for several heavy metals including mercury, whose resistance is often plasmid mediated. There was a biovariant difference in the incidence of resistance, and resistance to several metal ions was often observed together. There was no apparent relationship between resistance to heavy-metal salts and resistance to antimicrobial agents such as tetracycline.
In vitro activity of ciprofloxacin against aerobic gram-negative bacteria
Authors: Rudin J E , Norden C W , Shinners E M
Published: June 2012

For 177 gram-negative isolates, the MICs for ciprofloxacin ranged from 0.02 microgram/ml (Escherichia coli) to 0.31 microgram/ml (Pseudomonas aeruginosa). In time-kill curves, ciprofloxacin at 8 X the MIC almost completely killed 10(6) CFU of P. aeruginosa by 24 h. Ciprofloxacin at 4 X the MIC allowed bacterial regrowth by 24 h, with development of partial resistance to ciprofloxacin.
Evaluation of two broth disk methods for antibiotic susceptibility testing of anaerobes
Authors: Helstad A G , Hutchinson M A , Amos W P , Kurzynski T A
Published: June 2012

We evaluated the aerobic thioglycolate broth disk and the vaspar overlay broth disk methods for antibiotic susceptibility testing of 144 strains of anaerobes. For penicillin, carbenicillin, chloramphenicol, and metrionidazale, both broth disk methods yielded at least 95% agreement with results obtained by the National Committee for Clinical Laboratory Standards reference agar dilution procedure. For cefoxitin and clindamycin, the agreement was ca. 90%. Overall, the aerobic thioglycolate broth disk and vaspar overlay broth disk methods yielded agreements of 93.3 and 93%, respectively, with the National Committee for Clinical Laboratory Standards method.