bluuebunny/crossref_metadata_2025 huggingface dataset:
Penetration of cefazolin into normal and osteomyelitic canine cortical bone
Authors: Daly R C , Fitzgerald R H , Washington J A
Published: June 2012

The ability of cefazolin to cross the capillary membrane and its concentrations in the interstitial fluid spaces were studied in normal and osteomyelitic canine bone. The maximum extraction after a single capillary passage and the net extraction after 3 min, determined with triple-tracer indicator-dilution techniques, demonstrated that cefazolin readily traversed the capillaries of normal and osteomyelitic bone. These studies suggest that the altered pathophysiology of osteomyelitic tissue and the complex diffusional characteristics of cefazolin enhanced the ability of this agent to cross the endothelial cells lining the capillaries of osteomyelitic bone. Volume of distribution studies demonstrated that cefazolin was distributed in the plasma and interstitial fluid spaces of normal cortical bone. Although these spaces were increased 330 and 941% in osteomyelitic tissue, the distribution of cefazolin increased proportionally. There was a direct correlation between the calculated concentrations of cefazolin in the interstitial fluid spaces of normal and osteomyelitic cortical bone and the simultaneous serum levels in animals in which a steady-state equilibrium had been achieved. These studies suggest that a physiological barrier or concentration gradient for cefazolin does not exist in normal or osteomyelitic bone. Cefazolin can cross the capillary membranes of bone and achieve bactericidal concentrations in the interstitial fluid space of normal and osteomyelitic tissue.
Effect of combinations of acyclovir with vidarabine or its 5'-monophosphate on herpes simplex viruses in cell culture and in mice
Authors: Schinazi R F , Peters J , Williams C C , Chance D , Nahmias A J
Published: June 2012

The combination of various concentrations of acyclovir and vidarabine or its 5'-monophosphate usually produced an additive interaction with various strains of herpes simplex virus types 1 and 2 in Vero cells. Similarly, certain combinations of these drugs were more effective than the individual drugs in decreasing the mortality and increasing the mean day of death of mice inoculated intracerebrally with herpes simplex virus type 2. Neither antagonism nor interference was noted for any of the in vitro or in vivo combinations. The increased antiviral activity was determined not to be secondary to toxic effects of the drugs. Although viruses resistant to either vidarabine or acyclovir developed readily in cell culture, no evidence of cross-resistance was obtained. Furthermore, in the presence of the two drugs, mutants resistant to vidarabine, acyclovir, or vidarabine/acyclovir could not be isolated. These findings suggest that combinations with these antivirals, which are currently being evaluated singly for the therapy of severe forms of herpetic infection, could prove clinically useful if increasing numbers of resistant viral strains are observed.
In Vitro Activities of Thirteen β-Lactam Antibiotics Against
Chlamydia trachomatis
Authors: Muytjens Harry L. , Heessen Frans W. A.
Published: June 2012

The in vitro activity (minimal inhibitory concentration and minimal lethal concentration) of 13 β-lactam antibiotics against two laboratory strains of
Chlamydia trachomatis
was compared. No useful activity could be detected.
Diffusion of aminoglycoside antibiotics across the outer membrane of Escherichia coli
Authors: Nakae R , Nakae T
Published: June 2012

The diffusion of aminoglycoside antibiotics (gentamicin, kanamycin, streptomycin, fradiomycin, lividomycin, and mannosylparomomycin) through porin pores was examined in vitro by the liposome swelling technique, using vesicle membranes reconstituted from phospholipids and purified porin trimers. Results showed that aminoglycoside antibiotics diffuse through porin-pores very efficiently, as rapidly as hexoses and disaccharides, despite the fact that the molecular weights of the aminoglycosides used were higher than or close to the exclusion limit of porin pores. The susceptibility to aminoglycoside antibiotics of mutant strains producing 3 to 4% of porin was not significantly different from that of a strain producing a wild-type quantity of porin. These results were interpreted to mean that aminoglycoside antibiotics diffuse through porin-pores very efficiently. Therefore, the diffusion of these drugs through the mutant outer membranes producing 3 to 4% of porin is not a rate-limiting step for aminoglycoside diffusion and its action.
Interaction of povidone-iodine compounds, phagocytic cells, and microorganisms
Authors: Van den Broek P J , Buys L F , Van Furth R
Published: June 2012

The interaction between povidone-iodine, phagocytic cells, and microorganisms was studied. Three preparations of povidone-iodine were investigated: commercially available povidone-iodine solution Betadine, pure high-molecular-weight povidone-iodine as used in Betadine, and a low-molecular-weight povidone-iodine. Low concentrations of povidone-iodine (approximately 0.005%) have considerable activity in vitro. The concentrations used clinically (0.1 to 20%) are toxic for granulocytes and monocytes. Leukocytes reduce the in vitro microbicidal activity of povidone-iodine. No differences of any importance were found between the three preparations of povidone-iodine.
Comparison of radioimmunoassay and enzyme immunoassay methods in determining gentamicin pharmacokinetic parameters and dosages
Authors: Rotschafer J C , Morlock C , Strand L , Crossley K
Published: June 2012

Radioimmunoassay and enzyme immunoassay methods for analysis of serum gentamicin levels have been shown to be comparable. The purpose of this study was to determine if serum concentration-time data from the same patient assayed by radioimmunoassay and enzyme immunoassay would provide the same estimates for half-life, elimination rate constant, distribution volume, drug clearance, and gentamicin dose. A total of 103 pre- and postinfusion serum samples were obtained from 32 patients. The samples were divided and assayed by radioimmunoassay and enzyme immunoassay. Serum concentration-time data were fitted to a one-compartment model, and kinetic calculations were performed using the method of Sawchuk et al. (Clin. Pharmacol. Ther. 21:362-369, 1977). While good correlation was established between the two assay methods, significant (P less than 0.05) mean differences were seen in distribution volume (25%), gentamicin clearance (15%), and half-life (11%), using the quantitative data from both methods. Because of differences noted in these pharmacokinetic parameters, significant differences were also noted in dosage calculations. We conclude that there are differences in the pharmacokinetic parameters obtained using results from the radioimmunoassay and enzyme immunoassay. These differences also translate into significant differences between dosage recommendations when individualization of the gentamicin regimen is attempted.
Comparison of cefoperazone with penicillin, ampicillin, gentamicin, and chloramphenicol in the therapy of experimental meningitis
Authors: Scheld W M , Brodeur J P , Sande M A , Alliegro G M
Published: June 2012

Cefoperazone was compared with penicillin against Streptococcus pneumoniae, gentamicin against Escherichia coli, and ampicillin and chloramphenicol against Haemophilus influenzae in the therapy of experimental meningitis in rabbits. Meningitis was produced by intracisternal inoculation into cerebrospinal fluid, and all antibiotics were administered intravenously over 8 h in dosages that would achieve serum levels comparable to those found in humans. The mean percent penetration into purulent cerebrospinal fluid, expressed as (cerebrospinal fluid concentration/serum concentration) x 100%, was 2.6% for penicillin, 22.0% for gentamicin, 12.1% for ampicillin, 23.8% for chloramphenicol, and 6.4% for cefoperazone. The mean cerebrospinal fluid antibiotic concentrations exceeded the minimum bactericidal concentration for the test strain in each experimental model, except for ampicillin in experimental meningitis due to the beta-lactamase-producing H. influenzae. Cefoperazone produced a significantly faster bactericidal effect after 4 h of treatment when compared with penicillin (P = 0.037) and ampicillin (P = 0.01) in meningitis caused by S. pneumoniae and H. influenzae (ampicillin susceptible), respectively. In meningitis caused by E. coli, cefoperazone was significantly (P = 0.006) more rapidly bactericidal after 8 h of treatment when compared to gentamicin. In addition, cefoperazone was significantly more rapidly bactericidal than either ampicillin or chloramphenicol in experimental meningitis due to beta-lactamase-producing H. influenzae. Cefoperazone deserves further evaluation in the therapy of bacterial meningitis in humans.
Effect of allopurinol on Trypanosoma cruzi: metabolism and biological activity in intracellular and bloodstream forms
Authors: Berens R L , Marr J J , Steele da Cruz F S , Nelson D J
Published: June 2012

Allopurinol (4-hydroxypyrazolo [3,4-d]pyrimidine) is an effective agent in vitro against Trypanosoma cruzi. The important forms of this parasite, with respect to the pathogenesis of Chagas' disease in man, are the bloodstream (trypomastigote) and the intracellular forms. Experiments with radiolabeled allopurinol and analysis of the metabolic products of this compound by high-performance liquid chromatography showed that both the bloodstream and the intracellular forms of T. cruzi metabolize allopurinol in the same manner as has been shown for the epimastigotes in vitro. The metabolic pathways for pyrazolopyrimidines in the pathogenic forms were demonstrated with organisms isolated from infected animals and a tissue culture system infected with T. cruzi. Treatment of infected tissue culture with allopurinol eradicated the infection. This investigation implies that allopurinol may be useful in chemotherapy of T. cruzi infections, a supposition which has been borne out in one animal study.
Transferable resistance to cefoxitin in Bacteroides thetaiotaomicron
Authors: Rashtchian A , Dubes G R , Booth S J
Published: June 2012

Cefoxitin resistance, but not resistance to clindamycin, erythromycin, lincomycin, or tetracycline, was transferred by a conjugation-like process from Bacteroides thetaiotaomicron UN101, a clinical isolate haboring four kinds of plasmids, to other Bacteroides species. Of a sample of 20 cefoxitin-resistant transconjugants, 8 contained all 4 plasmids, 10 contained 1 to 3 plasmids, and 2 contained no plasmids.
Assay of amoxicillin and clavulanic acid, the components of Augmentin, in biological fluids with high-performance liquid chromatography
Authors: Foulstone M , Reading C
Published: June 2012

Augmentin is a new antibacterial formulation comprised of amoxicillin and the beta-lactamase inhibitor clavulanic acid. In the present paper, the use of high-performance liquid chromatography (HPLC) to provide a rapid assay of the components of Augmentin in body fluids is described. Clavulanic acid was assayed by reacting the sample with imidazole, which readily produces a derivative absorbing at 311 nm. This derivative chromatographs on reverse-phase HPLC columns clear of interfering components in both human serum and urine. Concentrations of clavulanic acid as low as 0.1 microgram/ml were readily detectable in human serum with this procedure. There was no interference from amoxicillin, amoxicillin penicilloic acid, or the acid and alkali degradation products of clavulanic acid when this assay system was used. Amoxicillin in body fluids was assayed directly by HPLC without derivatization. The same chromatographic conditions were employed for the assay of amoxicillin and the clavulanic acid derivative, simplifying the methodology. Amoxicillin, however, was determined of the antibiotic per ml. An alkali blanking procedure for amoxicillin and clavulanic acid is also described which allows the detection of any underlying peaks which may cochromatograph. The use of ultrafiltration to remove protein from serum samples before HPLC was successfully applied to the assay of clavulanic acid and amoxicillin. Ultrafiltration is not an essential procedure for these assays, but it prolongs column life and reduces interference in the amoxicillin assay. Results obtained by HPLC were compared with those obtained by using microbiological assays.
Effect of 2-alkynoic acids on in vitro growth of bacterial and mammalian cells
Authors: Konthikamee W , Gilbertson J R , Langkamp H , Gershon H
Published: June 2012

3-Decynoyl-N-acetylcystamine is known to inhibit the in vitro growth of Escherichia coli but not of yeasts or mammalian cells. Neither the free acid nor the 2 positional isomer is active (L. R. Kass, J. Biol. Chem. 243:3223-3228, 1968). Other studies have shown that 2-hexadecynoic acid is fungitoxic whereas most of the shorter chain isomers are inactive (H. Gershon and L. Shanks, Can J. Microbiol. 24:591-597, 1978). Since these studies suggested that positional or chain length isomers of the acetylenic acids may selectively inhibit the growth of microorganisms, the effect of the alkynoic acids on the in vitro growth of gram-positive and gram-negative bacteria was evaluated. 2-Hexadecynoic acid was found to be the most active species. This acid was bacteriostatic for all gram-positive bacteria tested. The acid was readily taken up by the treated cells and incorporated into the phospholipid fraction. When added to the culture medium, 2-hexadecynoic acid inhibited the growth of HeLa cells, but when mixed with an equivalent amount of palmitic acid, growth inhibition was not observed.
7-Hydroxytropolone: an inhibitor of aminoglycoside-2"-O-adenylyltransferase
Authors: Allen N E , Alborn W E , Hobbs J N , Kirst H A
Published: June 2012

Aminoglycoside-2"-O-adenylyltransferase was inhibited by 7-hydroxytropolone. Inhibition was competitive with respect to the cosubstrate ATP and appeared to require the unique vicinal arrangement of oxygens found in 7-hydroxytropolone. Combinations of 7-hydroxytropolone plus the appropriate aminoglycoside substrates were active against resistant bacteria possessing the adenylyltransferase. No potentiation was observed against other aminoglycoside-resistant or -susceptible strains. The fact that the inhibition of an aminoglycoside-modifying enzyme overcomes the poor uptake of aminoglycosides in resistant strains points to the singular importance of the inactivating enzyme as a determinant of resistance.
Role of serum protein binding and multiple antibiotic doses in the extravascular distribution of ceftizoxime and cefotaxime
Authors: Gerding D N , Van Etta L L , Peterson L R
Published: June 2012

The extravascular penetration of ceftizoxime and cefotaxime was studied in a rabbit subcutaneous Visking chamber model. Four rabbits, implanted with four chambers each, received each drug intramuscularly at a dose of 50 mg/kg every 3 hours for eight doses. Serum drug concentrations were measured after the eighth dose, and extravascular (chamber) concentrations were measured after the first and eighth doses. Cefotaxime (93% bound to rabbit serum proteins) demonstrated a much lower peak chamber-to-peak serum percent penetration after the first dose (20/163 = 13%) than did the less-bound (32%) ceftizoxime (21/52 = 40%, P less than 0.002). Similarly, the ratio of the chamber fluid area under the curve to the serum area under the curve was significantly lower for cefotaxime (15%) than for ceftizoxime (44%, P less than 0.002) after the first dose. Both agents approached equilibrium conditions between the intravascular and extravascular space by the eighth dose, and the ratios of chamber area under the curve to serum area under the curve of cefotaxime (76%) and ceftizoxime (79%) were similar. The peak-to-peak percent penetration of ceftizoxime (54%) was still significantly higher than that of cefotaxime (41%, P less than 0.01), although the chamber concentration of cefotaxime (66.2 micrograms/ml) was considerably higher than that of ceftizoxime (28.2 micrograms/ml). This study illustrates (i) dampened peak-to-trough antibiotic level fluctuation seen at extravascular sites as compared with measured serum concentrations, (ii) the large differences in extravascular penetration between single- and multiple-dose studies, and (iii) the importance of serum protein binding in the delay, but not the prevention, of extravascular drug distribution.
Susceptibility of Bacteroides spp. to heavy metals
Authors: Riley T V , Mee B J
Published: June 2012

The susceptibility of 105 strains of Bacteroides to arsenate, silver, nickel, cobalt, lead, cadmium, chromium, and mercuric ions was tested by using an agar dilution technique. All strains of Bacteroides were multiply resistant. Bacteroides fragilis was significantly more resistant to silver ions than other Bacteroides species and slightly more resistant to several other ions. Arsenate was the most active ion tested, with 75% of strains being susceptible. All 25 strains of B. fragilis tested against silver sulfadiazine were susceptible.
Comparative penetration of azlocillin and mezlocillin into cerebrospinal fluid of normal rabbits and rabbits with experimentally induced Pseudomonas aeruginosa meningitis
Authors: Hodges G R , Worley S E
Published: June 2012

The impacts of meningeal infection with Pseudomonas aeruginosa and route of drug administration on the penetration of azlocillin and mezlocillin into the cerebrospinal fluid of rabbits were evaluated. The penetration of both agents was increased to a similar degree in rabbits with meningitis compared with normal rabbits. The increase in penetration was greater after intravenous administration than after intramuscular administration.
Activity of tunicamycin against Trypanosoma brucei in vitro and in vivo
Authors: Casero R A , Porter C W , Bernacki R J
Published: June 2012

Tunicamycin, a specific inhibitor of glycoprotein biosynthesis, was evaluated for activity and chemotherapeutic potential against Trypanosoma brucei in vitro and in vivo. The inhibition of parasite incorporation of two radiolabeled macromolecular precursors, [methyl-3H]thymidine and D-[2-3H]mannose, was measured in short-term (4-h) microcultures. Mannose incorporation was inhibited over the concentration range of 0.01 to 10.0 microgram/ml, reaching 60% at the latter level. Thymidine incorporation was not affected. In vivo experiments indicated that a single dose of 2.0 mg of tunicamycin per kg can cure or significantly increase the life-span of mice of three different strains, each infected with T. brucei.
Prevention of human poliovirus-induced paralysis and death in mice by the novel antiviral agent arildone
Authors: McKinlay M A , Miralles J V , Brisson C J , Pancic F
Published: June 2012

Arildone, a novel antiviral agent which blocks virion uncoating, was assessed for its ability to prevent paralysis and death in mice infected intracerebrally with a lethal dose of human poliovirus type-2 (strain MEF). Intraperitoneal administration of arildone suspended in gum tragacanth prevented paralysis and death in a dose-dependent manner (minimal inhibitory dose = 32 mg/kg, twice daily) and protected animals from virus challenges in excess of 20 50% lethal doses. Oral medication with arildone solubilized in corn oil was similarly effective in preventing poliovirus-induced paralysis and death. Arildone was therapeutically effective even when intraperitoneal medication was delayed for 48 h postinfection. Analysis of the virus titers in the central nervous system tissues of animals infected with 200 50% lethal doses demonstrated that arildone reduced titers in the brain and spine by approximately 3 and 4 log10 PFU per g of tissue, respectively, implying that direct inhibition of virus replication was responsible for host survival. Arildone is the first antiviral agent capable of preventing poliovirus-induced death in mice. The efficient inhibition of poliovirus replication described here demonstrates the potential usefulness of uncoating blockers in the systemic treatment of viral diseases.
Synergism Between
N
-Formimidoyl Thienamycin and Gentamicin or Tobramycin Against Enterococci
Authors: Watanakunakorn Chatrchai , Tisone Joann C.
Published: June 2012

By the time-kill curve method, the combination of
N
-formimidoyl thienamycin and gentamicin showed synergism against 47 of 48 strains of enterococci, whereas the combination of
N
-formimidoyl thienamycin and tobramycin was synergistic against 46 strains.
Pharmacokinetics of cefotiam in normal humans
Authors: Daschner F D , Hemmer K A , Offermann P , Slanicka J
Published: June 2012

Doses of 0.5, 1.0, and 2.0 g of cefotiam were infused intravenously over a 15-min period in a crossover fashion to eight volunteers. Doses of 1.0 and 2.0 g were infused intravenously over periods of 30 and 60 min in a double crossover fashion to another eight volunteers. Serum concentrations fell rapidly from peak levels between 30 and 170 micrograms/ml at the end of the infusion to less than 1.0 micrograms/ml within 6 h after all regimens. The terminal half-life in plasma varied between 0.6 and 1.1 h. The slopes of the time-concentration curves with the different regimens showed different half-life data. The urinary excretion of cefotiam was mostly completed within 4 h of the beginning of drug administration. The pharmacokinetics of cefotiam were dose dependent. With the 2-g dose, the peak plasma concentrations and the values for the area under the curve were more than twice the values observed with 1 g; decreasing values of plasma clearance were observed with higher doses. Injection of cefotiam caused no immediate discomfort or reaction at the infusion site.
Pharmacokinetics and tissue penetration of azthreonam
Authors: Wise R , Dyas A , Hegarty A , Andrews J M
Published: June 2012

Six healthy male volunteers received 1 g of azthreonam each as an intravenous injection. Serial blood and cantharides-induced blister fluid samples were taken over the next 8 h. Urine samples were collected over 24 h. The concentration of azthreonam in serum was about 50 micrograms/ml at 0.5 h after injection and fell to 2 to 3 micrograms/ml at 8 h; the serum half-life was 1.93 h, and the volume of distribution was equivalent to 12% of the mean body weight. The plasma clearance was 89.0 ml/min, 73.7% of the dose being recovered in the urine within 24 h. Azthreonam rapidly penetrated blister fluid, reaching a maximum of 25.4 micrograms/ml at 1.8 h after administration.
Influence of gentamicin dose size on the efficacies of combinations of gentamicin and penicillin in experimental streptomycin-resistant enterococcal endocarditis
Authors: Wright A J , Wilson W R , Matsumoto J Y , Washington J A , Geraci J E
Published: June 2012

We have evaluated the benefits of low versus high doses of gentamicin combined with procaine penicillin (1.2 X 10(6) U three times daily) in the treatment of streptomycin-resistant experimental enterococcal endocarditis in rabbits. The mean peak serum gentamicin concentration in animals treated with low-dose gentamicin (0.75 mg/kg three times daily) was 3.06 micrograms/ml (range, 2.1 to 4.2 micrograms/ml), and it was 8.05 micrograms/ml (range, 4.5 to 16.1 micrograms/ml) in animals treated with high-dose gentamicin (2 mg/kg three times daily). The mean log10 colony-forming units of enterococci per gram of cardiac valve vegetation in animals treated with procaine penicillin combined with low- or high-dose gentamicin were 2.4 +/- 1.2 and 1.4 +/- 1.3, respectively (P = not significant) after 3 days of treatment and 1.7 +/- 1.2 and 1.7 +/- 1.5, respectively (P = not significant), after 5 days of therapy. The median peak serum bactericidal titer was 1:8 in animals treated with low- or high-dose gentamicin. We detected no significant difference between low- or high-dose gentamicin combined with procaine penicillin in the efficacy of treatment of streptomycin-resistant experimental enterococcal endocarditis.
Comparison of cefoperazone and cefoxitin concentrations in serum and pelvic tissue of abdominal hysterectomy patients
Authors: Bawdon R E , Hemsell D L , Guss S P
Published: June 2012

Cefoperazone and cefoxitin concentrations were determined in serum and pelvic tissue samples obtained at various intervals after a 2-g intramuscular dose. These levels were determined in 59 women scheduled for elective abdominal hysterectomy. Concentrations were measured by a new high-pressure liquid chromatography method which correlated with the microbiological assay. The mean times (+/- standard deviation) of specimen collection were 188.5 +/- 61 and 185.5 +/- 55 min for cefoperazone and cefoxitin, respectively. The mean serum levels (+/- standard deviation) were 60.8 +/- 18.0 and 14.6 +/- 8.6 micrograms/ml, respectively. For cefoperazone, the mean pelvic tissue concentration was 19.8 micrograms/g. The mean pelvic tissue concentration for cefoxitin was 7.8 micrograms/g. The ratio of tissue concentration to serum concentration varied from 0.220 to 0.469 for cefoperazone and from 0.176 to 1.031 for cefoxitin. Although the serum and tissue concentrations of cefoperazone were much higher than those of cefoxitin, a greater portion of cefoxitin remained in the tissue. The tissue levels of both cefoperazone and cefoxitin were above the minimum inhibitory concentration of most sensitive pathogens several hours after a single prophylactic dose of either antibiotic.
Mechanism of renal excretion of AM-715, a new quinolonecarboxylic acid derivative, in rabbits, dogs, and humans
Authors: Shimada J , Yamaji T , Ueda Y , Uchida H , Kusajima H , Irikura T
Published: June 2012

The mechanisms of the renal excretion of AM-715, a synthetic antimicrobial agent, were studied in rabbits, dogs, and humans. In both rabbits and humans, AM-715 clearance was greater than creatinine clearance and was profoundly decreased by the administration of probenecid. Thus, in these subjects, AM 715 was cleared by both tubular secretion and glomerular filtration. In dogs, however, the excretion ratio (close to unity), biological half-life, and stop-flow pattern of AM-715 were not affected by probenecid, indicating that the renal excretion of AM-715 took place mostly through glomerular filtration. These results suggest that renal excretion of AM-715 differs with animal species.
Multiple-dose pharmacokinetics of the monobactam azthreonam (SQ 26,776) in healthy subjects
Authors: Swabb E A , Sugerman A A , McKinstry D N
Published: June 2012

Azthreonam, a monocyclic beta-lactam highly active against aerobic gram-negative bacteria in vitro, was administered to four groups of nine healthy male volunteers in the following four regimens: 500 mg intravenously (i.v.) over 2 min every 8 h, 1,000 mg i.v. over 2 min every 8 h, 500 mg intramuscularly (i.m.) every 8 h, and 1,000 mg i.m. every 8 h for 7 days. Serial samples of serum and urine were assayed by microbiological methods, and urine samples collected during the high-dose i.m. regimen were assayed by a high-pressure liquid chromatographic procedure. Mean peak serum levels were 39 and 99 micrograms/ml after the initial i.v. doses and 18 and 39 micrograms/ml after the initial i.m. doses. There was no evidence of drug accumulation. Mean serum trough levels were 1.0 and 2.5 micrograms/ml during the two i.v. regimens and 1.8 and 3.8 micrograms/ml during the two i.m. regimens. The mean difference among Cmax, area under the curve from 0 to 8 h, and urinary recovery at 0 to 8 h on days 1 and 8 was less than 13% for each regimen. From the i.v. study, the mean steady-state volume of distribution was 0.21 liter/kg, the terminal half-life was 1.6 h, serum clearance was 1.7 ml min-1 kg-1, urinary recovery was 60%, and serum protein binding was 56%. An average of about 6% of a 1,000-mg i.m. dose was excreted in the 8-h urine collection on day 8 as the open beta-lactam ring hydrolysis product of azthreonam. The concentrations of azthreonam in serum were within the range required to inhibit growth of susceptible organisms in vitro.
Comparison of microtiter broth dilution and agar dilution methods for susceptibility testing of Eikenella corrodens
Authors: Goldstein E J , Cherubin C E , Shulman M
Published: June 2012

Eikenella corrodens is a slow-growing, capnophilic, gram-negative rod which often grows poorly in liquid media. Consequently, the agar dilution technique is the method of choice for susceptibility testing of E. corrodens. We report a new microtiter broth dilution method for susceptibility testing of E. corrodens which compared favorably with results obtained by the agar dilution technique. Minimal bactericidal concentrations correlated well with minimal inhibitory concentrations.
Nafcillin-induced platelet dysfunction and bleeding
Authors: Alexander D P , Russo M E , Fohrman D E , Rothstein G
Published: June 2012

This paper describes two cases of nafcillin-induced platelet dysfunction, with positive rechallenge data for one patient. Nafcillin resulted in abnormal bleeding times in both patients and a clinically apparent bleeding episode in one of the cases. Platelet function tests were performed on one patient during the initial therapy and after rechallenge with nafcillin. Platelet aggregation showed abnormal responses to ADP, collagen, and epinephrine. Platelet count and morphology were normal. Nafcillin should be recognized as another antibiotic which causes platelet function abnormalities and clinical bleeding episodes.
beta-Lactamase inhibitory activity of iodopenicillanate and bromopenicillanate
Authors: Neu H C
Published: June 2012

Iodopenicillanate and bromopenicillanate were shown to be effective inhibitors of a variety of beta-lactamases. Staphylococcus aureus isolates were synergistically inhibited by iodopenicillanate and bromopenicillanate combined with ampicillin. Methicillin-resistant S. aureus was not synergistically inhibited. Escherichia coli which possessed TEM beta-lactamase activity had a reduction in ampicillin minimal inhibitory concentration, but an E. coli isolate which had chromosomal beta-lactamase and a low ampicillin minimal inhibitory concentration showed no reduction in ampicillin minimal inhibitory concentration with either iodopenicillanate or bromopenicillanate. Of the Klebsiella isolates tested, 80% were synergistically inhibited by both iodopenicillanate and bromopenicillanate. Most Morganella isolates were synergistically inhibited by either iodopenicillanate or bromopenicillanate combined with ampicillin, as were many Salmonella, Shigella, Citrobacter diversus, and Citrobacter freundii isolates. No Pseudomonas aeruginosa isolates were synergistically inhibited by iodopenicillanate or bromopenicillanate. Preincubation did not improve the inhibitory activity of iodopenicillanate or bromopenicillanate.
Renal disposition of moxalactam in experimental animals as revealed by stop-flow analysis
Authors: Shimada J , Yamaji T , Miyahara T , Ueda Y , Kawabata T , Sugeno K , Yoshida T , Nakamura M
Published: June 2012

The mechanisms of moxalactam excretion were studied by stop-flow analysis in dogs, monkeys, and rabbits. In dogs, the amount of moxalactam excreted in the urine was almost equal to that estimated by glomerular filtration. There was no specific moxalactam peak corresponding to the p-aminohippuric acid (PAH) peak in the stop-flow patterns of the dogs. The PAH peak disappeared with administration of probenecid, but the moxalactam stop-flow pattern showed no change. In monkeys, no specific moxalactam peak corresponding to the PAH peak could be detected. In the stop-flow pattern of the rabbit, the peak moxalactam concentration corresponded with that of PAH and disappeared with probenecid. These results suggest that in dogs and monkeys renal excretion of moxalactam takes place mostly through glomerular filtration. In rabbits, however, there is a small renal tubular secretory component added to the primary element, glomerular filtration. These observations point to differences in the mechanisms of moxalactam excretion in different animal species.
Effect of Carbon Dioxide on Erythromycin
Authors: Goldstein Ellie J. C. , Sutter Vera L.
Published: June 2012

Exposure of erythromycin solutions to CO
2
or air for 18 h resulted in minimal deterioration under both conditions. Saturated disks exposed to the two atmospheres resulted in greater erythromycin deterioration, with slightly more deterioration occurring in the presence of CO
2
. Reduction of activity was greatest when assays were conducted in a CO
2
environment.
Norfloxacin penetration into subcutaneous tissue cage fluid in rabbits and efficacy in vivo
Authors: Rylander M , Norrby S R
Published: June 2012

The activity of norfloxacin was studied in vivo with steel net cages implanted subcutaneously in rabbits. Four weeks after implantation, two of four cages in each animal were inoculated with a strain of Escherichia coli (seven animals) or Klebsiella pneumoniae (six animals). Four animals in each group received oral treatment with norfloxacin for 7 days. Treatment was started 18 h after inoculation of the cages. Peak concentrations above the in vitro minimal inhibitory concentrations for the strains used were achieved in the fluid of 14 of 16 of the infected cages after the first norfloxacin dose. The penetration of norfloxacin into both infected and uninfected tissue cage fluid was significantly higher on treatment days 3 and 7 than on treatment day 1. No difference was observed between the concentrations in uninfected and infected cage fluids or between cage fluids infected with different organisms. The viable counts of E. coli and K. pneumoniae decreased from 2 X 10(3) to 2 X 10(8) CFU/ml of cage fluid to less than 10 CFU/ml in 10 of the infected cage fluids 12 h after the last dose of norfloxacin. Fluid from four cages still containing low numbers of viable bacteria at that time became free from bacteria (less than 10 CFU/ml) 1 to 4 days later. No regrowth was found in any cage fluid 7 days after the treatment period. The viable counts of E. coli or K. pneumoniae in five untreated control animals did not decrease during 8 to 14 days after inoculation of cage fluid. In comparison with cephalosporins and aminoglycosides studied previously with the same experimental method, norfloxacin penetrated better into cage fluid and more effectively reduced the viable counts of the organisms.
Cefsulodin pharmacokinetics in patients with various degrees of renal function
Authors: Matzke G R , Keane W F
Published: June 2012

The pharmacokinetics of cefsulodin were characterized in 19 patients with different degrees of renal function after a single 500-mg, 30-min intravenous infusion. Six subjects had a creatinine clearance (Clcr) of greater than 100 ml min-1 (group I), eight had a Clcr of between 12 and 42 ml min-1 (group II), and five had a Clcr of less than 10 ml min-1 (group III). Nine plasma and four urine samples were collected in the first 36 h. The plasma concentration-time data were fitted to a two-compartment open model. The mean beta-phase half-life was 1.77, 6.37, and 10.12 h in groups I, II, and III, respectively. A significant decline in plasma clearance (Clp) was also noted between the three groups: 136 to 49.6 to 27.2 ml min-1 in groups I, II, and III, respectively. Steady-state volume of distribution was 0.26 liter kg-1, regardless of renal function. The observed linear relationship between Clp and Clcr (Clp = 24.09 + 0.765 Clcr; r = 0.9566) can be utilized to revise dosage schedules for patients with any degree of renal impairment. The nonrenal clearance of cefsulodin was also noted to be significantly lower in groups II and III than in group I. Further investigations will be necessary to elucidate the mechanism(s) responsible for the decrease in the nonrenal clearance of cefsulodin.
Tn2011, a new transposon encoding oxacillin-hydrolyzing beta-lactamase
Authors: Nakazawa H , Mitsuhashi S
Published: June 2012

The type II penicillinase (oxacillin-hydrolyzing beta-lactamase, OXA-1) gene on plasmid Rms213 was transposed to various plasmids or to the host chromosome. The transposon bearing this gene, designated Tn2011, conferred resistance to ampicillin, streptomycin, sulfonamide, and mercuric chloride. By restriction endonuclease digestion and agarose gel electrophoresis, the molecular weight of Tn2011 was estimated to be 12.5 X 10(6). The transposition frequency of Tn2011 was about 10(-4) to 10(-5). The activity of type II penicillinase is related to the copy number of the replicon bearing Tn2011.
Effect of physiological manipulations on the chemotherapy of experimentally induced renal infection
Authors: Miller T , Phillips S
Published: June 2012

The belief that a favorable physiological milieu in the urinary tract may augment the effectiveness of antimicrobial agents used to treat urinary tract infections was examined by using an experimental model of Escherichia coli-induced renal infection in rats. The effect of manipulating urinary pH and flow on the antimicrobial activities of gentamicin, carbenicillin, ampicillin, nitrofurantoin and co-trimoxazole was assessed. In addition, a potential synergistic effect of the sequential administration of gentamicin and cephalothin in the eradication of renal infection was investigated. Although significant physiological alterations were achieved, these did not affect the efficacy of the antimicrobial agents studied, and therapeutic failures were common.
Differences in side effects of amantadine hydrochloride and rimantadine hydrochloride relate to differences in pharmacokinetics
Authors: Hayden F G , Hoffman H E , Spyker D A
Published: June 2012

In a double-blind, placebo-controlled study, the comparative toxicities and blood concentrations of amantadine hydrochloride and rimantadine hydrochloride were determined. Healthy, working adults ingested either 200 (n = 52) or 300 mg (n = 196) per day in divided doses for 4.5 days. Mean plasma drug concentrations at 4 h after the first dose were lower in rimantadine recipients given 100- (140 versus 300 ng/ml for rimantadine and amantadine, respectively; P less than 10(-5)) or 200-mg doses (310 versus 633 ng/ml; P less than 10(-5)). The plasma drug concentrations after the first dose correlated significantly with total symptom sources for both amantadine and rimantadine, but the plasma levels of toxic and nontoxic subjects overlapped extensively. At 300-mg/day dosage amantadine was associated more often with adverse central nervous system symptoms (33% of amantadine versus 9% of rimantadine recipients; P less than 0.001) and sleep disturbance (39 versus 13%; P less than 0.001), but not gastrointestinal symptoms (19.5 versus 16.0%). However, no differences between the drugs were noted in symptom frequency or scores in volunteers with similar plasma concentrations. Amantadine and rimantadine differ in their pharmacokinetics but not in their potential for side effects at comparable plasma concentrations.
Ceftazidime levels in human breast milk
Authors: Blanco J D , Jorgensen J H , Castaneda Y S , Crawford S A
Published: June 2012

Ceftazidime in the breast milk of 11 puerperal women were determined by bioassay. Each patient received 2 g of ceftazidime intravenously every 8 h for 5 days. The mean (+/- standard deviation) ceftazidime concentrations in the milk were: 3.8 +/- 2.0 (before the next dose), 5.2 +/- 3.0 (1 h after), and 4.5 +/- 1.7 micrograms/ml (3 h after). Ceftazidime was excreted in breast milk at relatively constant levels between days 2 and 4 of therapy.
Antimicrobial susceptibilities of bacteria associated with periodontal disease
Authors: Sutter V L , Jones M J , Ghoneim A T
Published: June 2012

A total of 193 bacterial strains were tested for their susceptibilities to 14 antimicrobial agents. Penicillin G was active at 2 U/ml against 98% of the oral isolates. Other antibiotics with good activity were cefoperazone, moxalactam, Sch 29,482, and clindamycin. Metronidazole was active against more than 90% of the anaerobic bacteria and Capnocytophaga but was inactive against most other microaerophilic and facultative strains.
Effects of Prolonged Cultivation in the Presence of Acyclovir on Recovery of Latent Herpes Simplex Virus from Human Trigeminal Ganglia
Authors: Lewis Marcia E. , Warren Kenneth G. , Jeffrey Verona M. , Tyrrell David L. J.
Published: June 2012

The continuous presence of acyclovir prevented the in vitro reactivation of latent herpes simplex virus from cultures of human trigeminal ganglia derived from 23 randomly selected cadavers. When acyclovir was withdrawn after 30 days, herpes simplex virus was recovered from 3 of 18 cases. Herpes simplex virus was recovered in 9 of 20 (45%) control cases.
In vitro activity of a group of broad-spectrum cephalosporins and other beta-lactam antibiotics against Chlamydia trachomatis
Authors: Hammerschlag M R , Gleyzer A
Published: June 2012

The activities of seven broad spectrum cephalosporins, four other beta-lactam antibiotics, and one monobactam against Chlamydia trachomatis were measured in a cell culture system. The minimal inhibitory concentration of four of the seven cephalosporins was greater than or equal to 128 micrograms/ml; those of the other three were from 16 to 32 micrograms/ml. Of the other agents, only mecillinam had activity against C. trachomatis comparable to that reported for ampicillin (minimal inhibitory concentration, less than or equal to 0.5 micrograms/ml).
Plasmid-Mediated Resistance to Trimethoprim-Sulfamethoxazole in
Salmonella krefeld
Strains Isolated in the United States
Authors: Mathewson John J. , Murray Barbara E.
Published: June 2012

Two types of transmissible plasmids which encode resistance to trimethoprim-sulfamethoxazole were found among five animal isolates of
Salmonella krefeld
. This is the first report of plasmid-mediated resistance to trimethoprim-sulfamethoxazole in
Salmonella
strains isolated in the United States.
Antibiotic resistance and serotypes of Streptococcus pneumoniae from patients with community-acquired pneumococcal disease
Authors: Liñares J , Garau J , Domínguez C , Pérez J L
Published: June 2012

From August 1978 to December 1981, 200 Streptococcus pneumoniae strains isolated from adult patients with pneumococcal disease were tested for susceptibility to penicillin G, erythromycin, clindamycin, tetracycline, and chloramphenicol by disk diffusion. Minimal inhibitory concentrations (MICs) were determined by agar dilution and broth dilution. The sources (numbers) of these isolates were blood (111), cerebrospinal fluid (30), sputum (26), pleural fluid (16), and miscellaneous (17). Of the 200 strains, 18 were partially resistant (MIC, 0.1 to 1 micrograms/ml) and 2 were resistant to penicillin. A total of 144 (72%) strains were tetracycline resistant, 87 of which had MICs of greater than or equal to 64 micrograms/ml. Ninety (45%) isolates exhibited various degrees of chloramphenicol resistance, with MICs ranging from 16 to 64 micrograms/ml. Five strains were resistant to erythromycin and clindamycin. Eleven penicillin-resistant strains were also resistant to chloramphenicol and tetracycline. Twenty-one different serotypes were encountered among the 120 typed strains studied. The most prevalent serotypes, in order of frequency, were 3, 1, 5, 19, 8, 6, 9, and 4, representing approximately two-thirds of the total number of isolates serotyped. These findings clearly indicate the need to perform antibiotic susceptibility testing in all cerebrospinal fluid isolates and other clinical significant isolates.
Clinical evaluation of moxalactam: evidence of decreased efficacy in gram-positive aerobic infections
Authors: Salzer W , Pegram P S , McCall C E
Published: June 2012

Moxalactam was used as initial, empirical therapy in 69 patients with a variety of serious bacterial infections, 32% of which were accompanied by bacteremia. Overall, the success rate was 83% and drug-related adverse effects were minimal. The drug was less efficacious in infections caused by aerobic gram-positive pathogens than it was in those caused by gram-negative pathogens. The following gram-positive organisms were associated with special problems during moxalactam therapy: Streptococcus pneumoniae (development of meningitis and a relapse of pneumonia with a more resistant strain), Staphylococcus epidermidis (in vivo emergence of moxalactam resistance, and the enterococci (failure of therapy and a fatal superinfection. Moxalactam performed well in infections caused by most gram-negative organisms, including aminoglycoside-resistant strains, but the previously reported emergence of gram-negative bacillary resistance to moxalactam during therapy was reconfirmed in our series with Serratia marcescens. The use of moxalactam in the treatment of gram-negative meningitis was further supported by a patient with meningitis-ventriculitis caused by Bacteroides fragilis who was cured with moxalactam after failure on chloramphenicol.
Reduction in fever and symptoms in young adults with influenza A/Brazil/78 H1N1 infection after treatment with aspirin or amantadine
Authors: Younkin S W , Betts R F , Roth F K , Douglas R G
Published: June 2012

During an outbreak of influenza A/Brazil/78 H1N1 infection, 47 volunteers with clinical and virological influenza of less than 2 days duration were treated in a randomized double-blind fashion for 5 days with 100 or 200 mg of amantadine daily or with 3.25 g of aspirin daily. The aspirin treatment group defervesced more rapidly (10.3 h versus 21.5 h and 23.6 h; P less than 0.01), but by the second daily follow-up visit, both groups of amantadine recipients exhibited greater symptomatic improvement. Bothersome side effects resulted in discontinuation of therapy by 35% of the aspirin treatment group but only 3% of the amantadine treatment group (P less than 0.05). Individuals who present to a physician during an influenza A epidemic with characteristic symptoms will experience symptomatic benefit from amantadine treatment, with negligible toxicity.
Clinical Pharmacology of Ceftriaxone in Patients with Neoplastic Disease
Authors: Salvador Patricio , Smith Ronald G. , Weinfeld R. E. , Ellis Daisy H. , Bodey Gerald P.
Published: June 2012

Pharmacological studies of ceftriaxone, a new semisynthetic cephalosporin, were conducted in 35 cancer patients. This antibiotic was administered in a variety of doses and schedules with no observed toxicity. Intramuscular administration of 500 mg of ceftriaxone to seven patients produced mean peak serum concentrations of 32.9 μg/ml 2.0 h after administration. The terminal serum half-life was 10.9 h. Intravenous infusion of 500 mg of ceftriaxone over 5 min to the same group of seven patients produced a mean peak concentration of the drug in serum of 83 μg/ml at the end of administration which decreased to 16.8 μg/ml at 8 h. A dose of 1 g of ceftriaxone given in identical fashion to the same group of seven patients produced mean peak concentrations in serum of 130 μg/ml at the end of administration and 17.3 μg/ml at 12 h. The mean percentages of drug recovered in urine 12 h after single intravenous doses of 500 mg and 1 g were 30 and 20%, respectively. A 1-g dose of ceftriaxone was administered every 8 h to 10 patients, and a 2-g dose was administered every 12 hours to 9 patients. Drug concentrations in serum were measured for each patient after drug administration on day 1, day 3 or 4, and day 7 or 8. The 1-g dose produced an observed mean peak concentration of 154 μg/ml and a mean terminal-phase half-life of 5.6 h on day 3 or 4. The 2-g dose produced a mean peak concentration in serum of 262 μg/ml and a terminal-phase serum half-life of 6.3 h on day 3 or 4. Continuous infusion studies were performed in nine neutropenic patients for up to 8 days by using a loading dose of 1 g over 30 min, followed by 2 g every 8 h. Mean concentrations in serum were maintained at about 135 μg/ml during the infusion period.