bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative pharmacokinetics of aminoglycoside antibiotics in guinea pigs
Authors: Chung M , Parravicini L , Assael B M , Cavanna G , Radwanski E , Symchowicz S
Published: June 2012

The pharmacokinetics of netilmicin, gentamicin, and tobramycin in plasma and in perilymph of guinea pigs were studied after a single intravenous injection of 40 mg/kg. Detailed pharmacokinetic analysis of the plasma drug concentration-time data up to 36 h after the intravenous dose revealed that the pharmacokinetics of the aminoglycoside antibiotics can be best described as a three-compartment open model. The disposition half-lives (t1/2) in plasma of the three antibiotics were comparable and within the following ranges: t1/2 alpha of 0.09 to 0.16 h; t1/2 beta of 0.88 to 1.01 h; and t1/2 gamma of 7.87 to 8.29 h. The volume of distribution in the central compartment and the total body clearance of netilmicin (294 ml/kg, 5.74 ml/min per kg) were greater than those of gentamicin (160 ml/kg, 3.40 ml/min per kg) and tobramycin (204 ml/kg, 4.63 ml/min per kg). Pharmacokinetic analysis of the perilymph drug concentration-time data indicated that all three antibiotics penetrated the perilymph readily, but netilmicin cleared from the perilymph compartment faster than gentamicin and tobramycin. The maximum perilymph drug concentrations were 4.17, 8.05, and 6.78 micrograms/ml and occurred at 1, 2, and 4 h for netilmicin, gentamicin, and tobramycin, respectively. The ratio of area under the curve of perilymph to plasma was lowest for netilmicin (0.27), followed by gentamicin (0.39) and tobramycin (0.57). These results suggest that the differences in pharmacokinetics and concentrations of netilmicin in the perilymph may account for less ototoxic liability of netilmicin compared with gentamicin and tobramycin.
Emergence of resistance to beta-lactam and aminoglycoside antibiotics during moxalactam therapy of Pseudomonas aeruginosa infections
Authors: Preheim L C , Penn R G , Sanders C C , Goering R V , Giger D K
Published: June 2012

In four patients with Pseudomonas aeruginosa infections, the infecting strain developed resistance to moxalactam during therapy with this drug. In addition, P. aeruginosa isolates from two of these four patients showed increased resistance to aminoglycosides. Isolates from a third patient acquired cross-resistance to other antipseudomonal beta-lactams. In three of the cases, disk susceptibility tests failed to detect the resistance that was demonstrated in broth dilution assays. Isolate identities were confirmed by serotyping. No new plasmids were found by agarose gel electrophoresis. The mechanisms for this resistance did not involve enzymatic antibiotic degradation. These findings suggest that currently available expanded-spectrum cephalosporin derivatives should probably not be used alone for most serious infections due to P. aeruginosa. They also suggest that strains with multiple antibiotic resistance may become more prevalent in hospitals if these drugs are used extensively.
Therapeutic activities of cefazolin, cefotaxime, and ceftazidime against experimentally induced Klebsiella pneumoniae pneumonia in rats
Authors: Bakker-Woudenberg I A , van den Berg J C , Michel M F
Published: June 2012

The efficacies of several dosage schedules of cefazolin, cefotaxime, and ceftazidime, started 12 or 36 h after infection, were examined in experimental pneumonia caused by Klebsiella pneumoniae in rats. The therapeutic activities of the cephalosporins were compared with the antibacterial activities in vitro and the serum concentration curves. The course of experimental pneumonia was rapid and characterized by tissue necrosis. Response to antimicrobial treatment was evaluated with respect to mortality and numbers of bacteria in lung (left lobe), blood, and pleural fluid. When antibiotic treatment was started early, i.e., 12 h after bacterial inoculation, cefotaxime and ceftazidime were equally effective and superior to cefazolin. Eleven doses of 10 mg of cefotaxime or ceftazidime per kg or 11 doses of 60 mg of cefazolin per kg were required to improve the survival rate. With a delay in administration to 36 h after inoculation, the efficacy of the cephalosporins decreased markedly. In the three dosages tested, cefazolin was ineffective. Survival improved with the administration of nine doses of 60 mg of cefotaxime per kg or nine doses of 10 mg of ceftazidime per kg. These results are not in accordance with the ratio of in vitro activities of cefotaxime and ceftazidime or the serum concentration curves.
Structure-activity relationships of new antiviral compounds
Authors: Bonina L , Orzalesi G , Merendino R , Arena A , Mastroeni P
Published: June 2012

In preliminary experiments, the compound 2-amino-5-(2-sulfamoylphenyl)-1,3,4-thiadiazole (G413) was shown to possess high activity against DNA viruses (herpes simplex viruses 1 and 2 and adenovirus 17) and RNA viruses (poliovirus 1, echovirus 2, and coxsackievirus B4). Experiments on the replicative cycle of poliovirus 1 and production of infectious RNA viruses demonstrate that this compound probably prevents assembly of virus particles by acting on structural proteins. In the present experiments, results concerning the activity of derivatives of G413 after side-chain modification are reported. Modification of the primary amine H to CH3 or CH2-CH = CH2 produced a loss of activity against DNA viruses, but inhibitory action on RNA viruses was preserved. Modification to CH2CH3 resulted in the loss of antiviral activity.
In vitro susceptibility of Mycobacterium fortuitum to N-formimidoyl thienamycin and several cephamycins
Authors: Cynamon M H , Palmer G S
Published: June 2012

The comparative in vitro activity of N-formimidoyl thienamycin, cefmetazole, cefoxitin, cefotetan (YM-09330), and moxalactam against 13 isolates of Mycobacterium fortuitum was evaluated by agar dilution susceptibility testing. N-Formimidoyl thienamycin inhibited 10 to 12 strains at 6.25 micrograms/ml, cefmetazole inhibited 12 of 13 strains at 12.5 micrograms/ml, cefoxitin inhibited 11 of 13 strains at 25 micrograms/ml, and cefotetan inhibited 11 of 13 strains at 50 micrograms/ml. Moxalactam was less active than the other compounds tested, inhibiting only 9 of 13 strains at 50 micrograms/ml.
Effects of ten milligrams of ampicillin per day on urinary tract infections
Authors: Redjeb S B , Slim A , Horchani A , Zmerilli S , Boujnah A , Lorian V
Published: June 2012

A total of 20 patients with symptomatic urinary tract infections (greater than 10(5) colony-forming units of Escherichia coli per ml of urine in addition to pyuria) received 10 mg of ampicillin and 2 liters of fluid daily for 3 days. After 2 days, 16 patients had culture-negative urine without pyuria. A total of 18 similar patients received only 2 liters of fluid for 3 days. On day 4, all had greater than 10(5) colony-forming units of E. coli per ml of urine and greater than 10(4) leukocytes per mm3 of urine.
Antimicrobial activity of amikacin combinations against Enterobacteriaceae moderately susceptible to third-generation cephalosporins
Authors: Jones R N , Packer R R
Published: June 2012

Enterobacteriaceae strains having elevated minimal inhibitory concentrations (greater than or equal to 2.0 to less than or equal to 32 micrograms/ml) of cefoperazone, cefotaxime, ceftazidime, and moxalactam were synergistically inhibited by amikacin combinations (54.1 to 69.6% occurrence). Indifference was rare (8.1% for moxalactam), and true antagonistic interactions were not observed. Strains resistant or susceptible to these new cephalosporins were also synergistically inhibited by the addition of amikacin, reducing resistant cephalosporin minimal inhibitory concentrations to clinically achievable levels.
Effect of furosemide on aminoglycoside-induced nephrotoxicity and auditory toxicity in humans
Authors: Smith C R , Lietman P S
Published: June 2012

We analyzed data from three prospective, controlled, randomized, double-blind clinical trails to determine whether furosemide increases the nephrotoxicity and auditory toxicity of aminoglycosides. All patients who received at least 72 h of treatment and who had no other cause for nephrotoxicity or auditory toxicity were included in the analysis. Nephrotoxicity developed in 10 of 50 (20.0%) patients given furosemide and in 38 of 222 (17.1%) patients not given furosemide (P greater than 0.3). Auditory toxicity developed in 5 of 23 patients (21.7%) given furosemide and in 28 of 119 patients (23.5%) not given furosemide (P greater than 0.3). In each case, the groups receiving and not receiving furosemide did not differ in mean age, initial creatinine, duration of aminoglycoside therapy, mean change in auditory acuity or creatinine, mean number of days to the development of toxicity, the frequency with which gentamicin, tobramycin, amikacin, or cephalothin was administered, or the mean predose and 1-h postdose plasma aminoglycoside levels. We conclude that furosemide use should not be considered a major risk factor for the development of aminoglycoside-induced nephrotoxicity or auditory toxicity.
Determination of minimum bactericidal concentrations of oxacillin for Staphylococcus aureus: influence and significance of technical factors
Authors: Taylor P C , Schoenknecht F D , Sherris J C , Linner E C
Published: June 2012

The minimum bactericidal concentration of oxacillin for Staphylococcus aureus was shown to be considerably influenced by technical and definitional factors, particularly by the survival of some organisms on the walls of test tubes and by the growth phase of the inoculum. Attention to technical detail greatly improved reproducibility, and log-phase cultures of all strains showed greater than 99.9% killing in 24 h, at or close to the minimum inhibitory concentration, including eight strains described as tolerant. Some strains showed the paradoxical phenomenon of having more survivors in higher concentrations above the minimum bactericidal concentration. An accepted reference minimum bactericidal concentration procedure is needed for establishing clinical correlates and for a review of endpoint criteria. Routine minimum bactericidal concentration tests on S. aureus should be interpreted with great caution.
Conjugational transfer of gentamicin resistance plasmids intra- and interspecifically in Staphylococcus aureus and Staphylococcus epidermidis
Authors: McDonnell R W , Sweeney H M , Cohen S
Published: June 2012

We have previously reported the transfer of gentamicin resistance (Gmr) plasmids in a mixed culture inter- and intraspecifically between strains of Staphylococcus aureus and Staphylococcus epidermidis isolated at Michael Reese Hospital (Jaffe et al., Antimicrob. Agents Chemother. 21:773-779, 1982). We have now shown that representatives of these plasmids were transferred between apparently nonlysogenic strains of S. aureus either in mixed culture in broth or by filter-mating on agar medium. The mechanism of transfer appeared to be conjugation. A transferable Gmr plasmid (pSH8) mobilized or cotransferred a tetracycline R-plasmid and a chloramphenicol R-plasmid that were not independently transferable. The transfer of Gmr plasmids was accompanied by a high incidence of deletion mutations with varied loss of plasmid resistance determinants and, with some mutants, loss of the ability to effect self-transfer. Restriction endonuclease digestion of pSH8 and its deletion mutants made it possible to assign the property of self-transfer to a specific segment of the pSH8 genome and provided the basis for a physical and genetic map of that plasmid. Similar Gmr plasmids from S. aureus strains isolated in locations remote from Michael Reese Hospital had resistance determinants and transfer properties comparable to those of pSH8. Our observations provide evidence for the conjugal transfer of some staphylococcal plasmids, apparently independent of the presence of phage. This mechanism may be of significance in the intra- and interspecific dissemination of resistance to aminoglycosides and other antibiotics in Staphylococcus spp.
In vitro susceptibility of Haemophilus somnus to 33 antimicrobial agents
Authors: Sugimoto C , Mitani K , Nakazawa M , Sekizaki T , Terakado N , Isayama Y
Published: June 2012

Minimal inhibitory concentrations of 33 antimicrobial agents for Haemophilus somnus were determined by the agar dilution method. The tested H. somnus strains were highly susceptible to penicillin G, ampicillin, colistin, and novobiocin. They were not susceptible to spiramicin and sulfadimethoxine, and streptomycin-resistant strains were found.
Toxicity of amphotericin B, miconazole, and ketoconazole to human granulocyte progenitor cells in vitro
Authors: Meeker T C , Siegel M S , Shiota F M , Crowley J J , McGuffin R W
Published: June 2012

Granulocyte progenitor cells were grown in culture with amphotericin B, miconazole, and ketoconazole. Significant suppression of progenitor cell growth could be demonstrated with all three drugs at increasing concentrations. No additive suppression was seen when amphotericin B and ketoconazole were combined.
Feasibility of Gentamicin Measurement in Icteric Sera by the Syva EMIT System
Authors: Witebsky Frank G. , Selepak Sally T.
Published: June 2012

Total serum bilirubin concentrations of up to 45 mg/dl did not have a significant effect on the accuracy of serum gentamicin measurements by the Syva EMIT system with gentamicin concentrations of up to 14 μg/ml.
Limitations of a fluorescence assay for studies on tetracycline transport into Escherichia coli
Authors: Smith M C , Chopra I
Published: June 2012

Transport of tetracycline into Escherichia coli was studied by two methods, one involving an absolute determination of accumulated drug and the other a fluorescence assay. Tetracycline uptake was nonsaturable when assayed by the absolute method, but fluorescence enhancement was maximal at an initial external tetracycline concentration of about 200 microM. The two transport assays also gave different results for the pH optimum of tetracycline transport. The absolute method indicated a pH optimum of 7.0 to 8.0, whereas the fluorescence method gave a value of 5.5 to 6.0. These data indicate that the fluorescence assay is of limited value in certain situations.
Antimicrobial resistance and incompatibility groups of R plasmids in Salmonella typhimurium isolated from human sources in Bombay from 1978 to 1980
Authors: Rangnekar V M , Banker D D , Jhala H I
Published: June 2012

Salmonella typhimurium isolated in Bombay from fecal samples of 145 patients suffering from gastroenteritis (group 1) and from the cerebrospinal fluid, feces, or blood of 42 patients with systemic salmonellosis (group 2) were examined for the antimicrobial resistance and incompatibility groups of their R plasmids. Multiple drug resistance was encountered in 88.9% of the isolates from group 1 and in all the isolates from group 2. The resistance found was mainly against ampicillin, chloramphenicol, kanamycin, streptomycin, sulfonamides, and tetracycline. In addition to these resistances, a number of isolates were also resistant to sulfamethoxazole-trimethoprim and gentamicin. The overall isolation frequency of strains resistant to these last drugs was significantly higher in group 2. The drug resistance in 95.3% of the isolates from group 1 and in all the isolates from group 2 was plasmid mediated. Incompatibility grouping of the R plasmids and phage typing of the isolates indicated that a clone of S. typhimurium with phage type pattern 66/122/untypable carrying Tra- IncF1me, Tra- Inc1, and Tra- Inc2 plasmids was most prevalent in Bombay from 1978 to 1980, and examples of this clone, especially those resistant to sulfamethoxazole-trimethoprim and gentamicin, were most often responsible for severe septicemic infection. A majority of the remaining S. typhimurium isolates were untypable and harbored plasmids of groups IncC, IncF1me, IncFII, IncH1, IncH2, IncI1 and IncI2; these isolates were rarely associated with systemic infection.
In vitro antibacterial activity of SM-1652, a new broad-spectrum cephalosporin with antipseudomonal activity
Authors: Fukasawa M , Noguchi H , Okuda T , Komatsu T , Yano K
Published: June 2012

SM-1652 (sodium 7-[D(-)-alpha-(4-hydroxy-6-methylpyridine-3-carboxamido)-alpha-(4-hydroxyphenyl)acetamido]-3-[(1-methyl-1H-tetrazol-5-yl) thiomethyl]-3-cephem-4-carboxylate) is a new semisynthetic cephalosporin derivative with a broad spectrum of antibacterial activity. Its in vitro activity against gram-positive bacteria was comparable to that of cefazolin. SM-1652 exceeded cefazolin in potency and broadness of antibacterial activity against such Enterobacteriaceae as indole-positive Proteus spp., Enterobacter cloacae, and Serratia marcescens. A remarkable feature of the spectrum of SM-1652 is its high activity against Pseudomonadaceae. Against 200 clinical isolates of Pseudomonas aeruginosa, SM-1652 was significantly more active than cefoperazone, cefotaxime, and sulbenicillin and as active as cefsulodin. The activities of SM-1652 against Pseudomonas maltophilia and Pseudomonas cepacia were superior to those of cefoperazone, cefotaxime, cefsulodin, sulbenicillin, and gentamicin. SM-1652 was relatively stable to hydrolysis with plasmid-mediated penicillinases and cephalosporinases produced by gram-negative bacteria.
pH-dependent oxacillin tolerance of Staphylococcus aureus
Authors: Venglarcik J S , Blair L L , Dunkle L M
Published: June 2012

A proportion of clinical isolates of Staphylococcus aureus exhibit resistance to bactericidal activity of certain antibiotics, despite normal susceptibility to inhibition. This phenomenon is termed "tolerance." The methodology used to determine tolerance varies greatly. To clarify the relationship between laboratory methodology and tolerance, we determined the minimal bactericidal concentrations and minimal inhibitory concentrations for 20 clinical isolates by two methods. Inocula were prepared by either 3-h growth of the organism in Mueller-Hinton broth or overnight (22 to 24 h) cultures in Trypticase soy broth (BBL Microbiology Systems, Cockeysville, Md.). All inocula were plated for colony counts and tested for pH. An American Type Culture Collection (Rockville, Md.) reference strain was included in all tests for standardization. Tolerance was defined by the strictest criterion, i.e., a minimal bactericidal concentration/minimal inhibitory concentration ratio of greater than or equal to 100. With the first method, none of the 20 isolates displayed tolerance (mean inoculum pH, 7.15). When inocula were grown in Trypticase soy broth with overnight incubation, 35% (7 of 20) showed tolerance (mean inoculum pH, 6.22). There was a significant association between the decreased bactericidal capacity at high oxacillin concentrations and overnight incubation in Trypticase soy broth (P less than 0.01). We suggest that tolerance in staphylococci is in some way related to the pH value of the inoculating culture. Such pH-induced tolerance may have a clinical corollary in sequestered infections where the pH is acidic.
In Vitro Susceptibility of 50 Non-β-Lactamase-Producing
Neisseria gonorrhoeae
Strains to 12 Antimicrobial Agents
Authors: Rodríguez J. , Fuxench-Chiesa Z. , Ramírez-Ronda C. H. , Kouri Y. , Cuevas R. , Nevarez M. , Pérez M.
Published: June 2012

The in vitro activities of six commonly used antibiotics and six newer β-lactam agents were determined in 50 consecutive clinical isolates of β-lactamase-negative
Neisseria gonorrhoeae
. The gonococci isolated were notably resistant to penicillin, ampicillin, erythromycin, and tetracycline, whereas all of the strains were susceptible to the newer β-lactam agents cefoxitin and spectinomycin.
Ceftriaxone therapy of serious bacterial infections in adults
Authors: Bittner M J , Dworzack D L , Preheim L C , Tofte R W , Crossley K B
Published: June 2012

We evaluated the efficacy and safety of ceftriaxone in 50 adults with serious infections, usually giving 1 g every 12 h. Of the 35 patients who could be evaluated for clinical efficacy, 15 had failed on previous therapy, 15 had nosocomial infections, and all but 1 had underlying diseases. One patient had three sites of infection. Favorable responses were seen in 34 of 37 infections, including 11 of 13 respiratory tract infections, all 7 urinary tract infections, all 12 skin and soft tissue infections, 1 of 2 bone and joint infections, a catheter-related septicemia, a liver abscess, and an otitis media and externa. Favorable bacteriological responses were seen for 48 of 58 organisms. This included 6 of 7 Staphylococcus aureus strains, 14 of 16 other aerobic gram-positive cocci, 18 of 20 Enterobacteriaceae, 6 of 9 Pseudomonas aeruginosa, and 1 of 2 anaerobes. Peak plasma ceftriaxone levels on day 1 were 152 micrograms/ml by bioassay and 78 micrograms/ml by high-pressure liquid chromatography. Four of the 31 initial isolates of aerobic gram-negative rods developed resistance to ceftriaxone on disk diffusion testing. Diarrhea occurred in 3 of 50 patients. All three had received a higher than usual dose. Drug administration was stopped twice, once for a thrombocytopenia and once for a thrombocytopenia with leukopenia. Neither problem could be attributed exclusively to ceftriaxone. Other adverse reactions were eosinophilia, abdominal pain, inguinal candidiasis, and nonsuppurative phlebitis. Even among debilitated adults, ceftriaxone was safe and effective in a twice daily regimen.
Moxalactam Therapy of Bacterial Meningitis in Adults
Authors: Uwaydah Marwan , Tannir Nizar , Kantarjian Hagop , Osseiran Maher , Bal'a Farid
Published: June 2012

The therapeutic efficacy and attainable cerebrospinal fluid (CSF) concentrations of moxalactam, administered by intravenous drip in a dose of 2 g every 4 to 8 h, were evaluated in seven adult patients with bacterial meningitis.
Streptococcus pneumoniae, Staphylococcus aureus, Pseudomonas aeruginosa
, and
Acinetobacter calcoaceticus
var.
anitratus
, each caused infection in four patients, whereas
Escherichia coli
was the cause of infection in the other three patients. The mean moxalactam concentration in CSF was 14.7 μg/ml (range, 4.7 to 38 μg/ml) in the lumbar samples and 12.1 μg/ml (range, 4.4 to 27 μg/ml) in the ventricular samples. Depending on the time after antibiotic administration, the ratio of CSF to serum concentrations varied from 6.6 to 160%. Satisfactory improvement and negative CSF cultures were initially noted in all seven patients. Six patients were ultimately cured, and the death of the patient with
Pseudomonas
meningitis could not be clearly attributed to uncontrolled infection.
Urinary Recovery of
N
-Formimidoyl Thienamycin (MK0787) as Affected by Coadministration of
N
-Formimidoyl Thienamycin Dehydropeptidase Inhibitors
Authors: Norrby S. R. , Alestig K. , Björnegård B. , Burman L. Å. , Ferber F. , Huber J. L. , Jones K. H. , Kahan F. M. , Kahan J. S. , Kropp H. , Meisinger M. A. P. , Sundelof J. G.
Published: June 2012

N
-Formimidoyl thienamycin (MK0787) undergoes renal metabolism by a dipeptidase, dehydropeptidase I, located on the brush border of the proximal tubular cells. The effects of two inhibitors (MK-789 and MK-791) of dehydropeptidase I on the pharmacokinetics of
N
-formimidoyl thienamycin were studied in 41 healthy subjects receiving various combinations of
N
-formimidoyl thienamycin and MK-789 or MK-791. Both inhibitors affected the plasma kinetics of
N
-formimidoyl thienamycin only to a small extent. Plasma concentrations and the area under the plasma concentration curve increased about 20% with a proportional decrease in plasma clearance. Plasma half-life was not altered significantly. Coadministration of MK-789 or MK-791 resulted in uniform and marked increases in urinary recovery and renal clearance of
N
-formimidoyl thienamycin. Thus, at an
N
-formimidoyl thienamycin/MK-791 ratio of 1:0.25 or higher, the urinary recovery was about 72% in all subjects, whereas it varied between 7.7 and 43% when
N
-formimidoyl thienamycin was given alone. The ratio of the
N
-formimidoyl thienamycin and MK-791 doses affected response. At relatively higher doses of MK-791, significant increases of
N
-formimidoyl thienamycin urinary recovery, renal clearance, and urine concentrations occurred during the later part of the 10-h observation period after each administration. At a 1:1 ratio of the two drugs, the inhibition of renal metabolism of
N
-formimidoyl thienamycin was maintained for at least 8 h, whereas renal clearance declined as soon as 4 h after the administration of a 1:0.25 ratio. The results indicated that MK-789 and MK-791 alter the renal excretion of
N
-formimidoyl thienamycin from glomerular filtration plus tubular secretion to glomerular filtration only, possibly by competitively inhibiting the penetration of
N
-formimidoyl thienamycin into the proximal tubular cells.
Rapid Method for Screening Large Numbers of
Escherichia coli
Colonies for Production of Plasmid-Mediated β-Lactamases
Authors: Wolfson John S. , Hooper David C. , Swartz Morton N. , Swartz Mark D. , McHugh Gail L.
Published: June 2012

A rapid, simple assay for screening large numbers of
Escherichia coli
colonies for production of certain plasmid-mediated β-lactamases (including TEM-1, TEM-2, HMS-1, SHV-1, OXA-1, PSE-1, PSE-4, and CEP-2) is described. The technique, a modification of the method of Slack et al. for detection of β-lactamase in limited numbers of
Haemophilus influenzae
clinical isolates (Lancet ii:906, 1977), uses filter paper impregnated with benzylpenicillin and a pH indicator dye (bromocresol purple) that changes color in the presence of β-lactamase activity. The test paper is briefly applied to an agar surface containing bacterial colonies which are subsequently scored individually on the paper by color: yellow indicates the presence of β-lactamase, dark green its absence, and variegation (yellow and dark green) a mixed population. Concordance of the results of this assay with those of replica plating for antibiotic resistance was over 99%. Hundreds of colonies per plate can be scored quickly and remain viable for further evaluation. The assay appears to be useful for studies of the stability of plasmids encoding β-lactamases and in cloning with vectors such as pBR322 in which insertion of DNA fragments can be detected by inactivation of the β-lactamase gene. Whenever the assay is to be used, results should always be confirmed initially by another method, such as replica plating, because the test paper assay does not detect three β-lactamases (OXA-2, OXA-3, and PSE-2) and also would miss intrinsic penicillin resistance.
Comparative Concentrations of Cefoxitin in Human Lungs and Sera
Authors: Perea Evelio J. , Garcia-Iglesias Mercedes C. , Ayarra Javier , Loscertales Jesús
Published: June 2012

Eleven patients about to undergo pulmonary surgery received a bolus injection of 1 g of cefoxitin. The concentrations of cefoxitin in the serum 1 and 2 h after dosage were 38.5 ± 1.89 and 23.7 ± 2.56 μg/ml; the lung concentrations at the respective times were 12.6 ± 0.7 and 10.06 ± 0.43 μg/ml.
Comparative efficacy of cefmenoxime versus penicillin in the treatment of gonorrhea
Authors: Obaid S R , Khan M Y , Simpson M L , Gruninger R P , Wigren D I
Published: June 2012

A total of 121 men with complicated infections caused by beta-lactamase-negative Neisseria gonorrhoeae were included in this study. They were randomly assigned to regimens of either cefmenoxime (1.0 g) or procaine penicillin G (4.8 X 10(6) U) intramuscularly. Only the penicillin group also took 1.0 g of probenecid orally. A total of 99 patients completed the study, providing data from 108 infected sites. In the cefmenoxime group, there were 49 urethral, 1 rectal, and 2 pharyngeal infections; in the penicillin group, there were 49 urethral, 4 rectal, and 3 pharyngeal infections. In the cefmenoxime group, all except one urethral infection were eradicated. This patient admitted having had sexual intercourse during the follow-up period and was considered to be reinfected. In the penicillin group, all except one pharyngeal infection were cured. No adverse reactions were noted in either group. In this study, cefmenoxime was as effective as penicillin in the treatment of gonococcal urethritis in men.
Chloramphenicol kills Haemophilus influenzae more rapidly than does ampicillin or cefamandole
Authors: Schauf V , Green D C , van der Stuyf L , Riff L
Published: June 2012

The bactericidal effects of chloramphenicol and three beta-lactams (ampicillin, cefamandole, and penicillin G) were measured for 27 strains of Haemophilus influenzae type b isolated from the blood or cerebrospinal fluid of infected infants. Of the ampicillin-susceptible strains, 75% were killed by less than 2.0 micrograms of each antibiotic per ml; however, the concentration of the beta-lactam agents required for bactericidal activity was higher than that required for inhibitory activity. Chloramphenicol was the only agent which had no marked discrepancy between inhibitory and bactericidal concentrations regardless of beta-lactamase production. Importantly, chloramphenicol was more rapidly bactericidal than either ampicillin or cefamandole. The bactericidal requirement of ampicillin was increased by the presence of chloramphenicol for about one-third of the isolates examined. Neither the inhibitory nor the bactericidal activity of chloramphenicol was influenced by ampicillin. Synergy occurred for only two beta-lactamase-positive isolates. The more rapid bactericidal action of chloramphenicol persisted even in the presence of ampicillin. The rapid bactericidal action of chloramphenicol with or without ampicillin supports the use of chloramphenicol alone or with ampicillin for H. influenzae infections.
Inhibition of herpes simplex virus DNA synthesis by pokeweed antiviral protein
Authors: Teltow G J , Irvin J D , Aron G M
Published: June 2012

Pokeweed antiviral protein at a concentration of 3 microM inhibited both the synthesis and release of infectious herpes simplex virus type 1 in cell culture by 90 and 99%, respectively. Addition of pokeweed antiviral protein to Vero cell monolayers before virus infection was 10 to 15% more effective in reducing virus yields than was the simultaneous addition of the antiviral protein with virus inoculum. Viral DNA synthesis was inhibited by 90% in cells which had been exposed to the antiviral protein, whereas cellular DNA synthesis was unaffected. No significant inhibition in the synthesis of the majority of viral infected-cell polypeptides was observed early postinfection (7 h), with the exception of infected cell polypeptides 4 and 41, whose syntheses were reduced by 38 and 25%, respectively. At 9 to 21 h postinfection, however, the synthesis of individual infected cell polypeptides was reduced by 48 to greater than 99%.
Antimycoplasmal activity of ofloxacin (DL-8280)
Authors: Osada Y , Ogawa H
Published: June 2012

Ofloxacin (DL-8280; (+/-)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1- pipera-zinyl)-7-oxo-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid) showed a broader spectrum and a greater potency of antimycoplasmal activity than did pipemidic acid, norfloxacin, tetracyclines, and lincomycin, but was inferior to erythromycin. Its mycoplasmacidal potency against clinical isolates of Mycoplasma pneumoniae was also greater than that of other quinolones and tetracyclines.
In vitro antimicrobial activity of eight new beta-lactam antibiotics against penicillin-resistant Neisseria gonorrhoeae
Authors: Kerbs S B , Stone J R , Berg S W , Harrison W O
Published: June 2012

Increasing numbers of cases of penicillin-resistant gonorrhea necessitate the evaluation of new antibiotics for treatment of this disease. We tested the susceptibility of 92 penicillinase-producing (PP) Neisseria gonorrhoeae isolates and 88 penicillin-susceptible (PS) isolates to eight new beta-lactam antibiotics. The minimal inhibitory concentrations of these antibiotics were determined by the agar plate method. PP and PS N. gonorrhoeae isolates were susceptible to clinically achievable levels of all antibiotics tested. There were, however, marked differences among the drugs with regard to the concentration required to inhibit growth. The PP N. gonorrhoeae isolates were extremely susceptible to ceftriaxone, ceftizoxime, and cefotaxime, highly susceptible to moxalactam and cefoperazone, and less susceptible to cefoxitin, ceforanide, and cefonicid (geometric mean minimal inhibitory concentrations were 0.002, 0.003, 0.007, 0.03, 0.07, 0.6, 2.4, and 3.1 micrograms/ml, respectively). Although this in vitro study showed PP N. gonorrhoeae isolates to be comparatively more susceptible to ceftriaxone, ceftizoxime, and cefotaxime than to the other antibiotics, these results may not correlate with clinical efficacy.
Oral bioavailability of the monobactam aztreonam (SQ 26,776) in healthy subjects
Authors: Swabb E A , Sugerman A A , Stern M
Published: June 2012

To investigate the oral bioavailability of aztreonam (SQ 26,776), we administered single 500-mg doses of this monobactam as an oral solution, as two 250-mg capsules, and as a 3-min intravenous infusion to 15 healthy male subjects at 1-week intervals according to a three-way crossover study design. Serum and urine samples were assayed by microbiological methods. The absolute systemic bioavailability of each oral formulation, defined as the ratio of areas under the serum concentration-time curves after oral and intravenous administration, was less than 1%. Peak serum levels achieved with oral solution, capsule, and intravenous infusion were 0.15, 0.14, and 56.7 micrograms/ml, respectively, and cumulative urinary excretion was 0.7, 0.6, and 68% of the administered dose, respectively.
In vitro activity of Bay 09867, a new quinoline derivative, compared with those of other antimicrobial agents
Authors: Wise R , Andrews J M , Edwards L J
Published: June 2012

The in vitro activity of Bay 09867, a new quinoline derivative, was compared with those of norfloxacin, nalidixic acid, ceftazidime, cefaclor, cefuroxime, gentamicin, and other antimicrobial agents, when appropriate, against 410 recent clinical isolates. The minimal inhibitory concentrations of Bay 09867 for 90% of Enterobacteriaceae, Pseudomonas aeruginosa, Haemophilus influenzae, Neisseria gonorrhoeae, streptococci, Staphylococcus aureus, and Bacteroides fragilis strains were between 0.008 and 2 micrograms/ml. Bay 09867 was considerably more active against the gram-negative bacteria tested than were other agents tested. Gentamicin-resistant Enterobacteriaceae, P. aeruginosa, and methicillin-resistant S. aureus were highly susceptible to Bay 09867. Strains less susceptible to nalidixic acid and norfloxacin tended to be less susceptible to Bay 09867. The protein binding of Bay 09867 was about 20%.
Effects of hepatic function on vancomycin clinical pharmacology
Authors: Brown N , Ho D H , Fong K L , Bogerd L , Maksymiuk A , Bolivar R , Fainstein V , Bodey G P
Published: June 2012

Using a recently developed radioimmunoassay, we performed 15 vancomycin pharmacology studies in cancer patients with infections. Vancomycin (500 mg) was infused intravenously for 30 min every 6 h for up to 7 days. The plasma disappearance curve was biphasic, with an initial half-life of less than 30 min. The second half-life (t1/2 beta), not dose related, varied from 1.4 to 231 h among the patients. In six studies of patients with normal hepatic functions, the t1/2 beta was 2.6 h; the rate of total clearance was 162 ml/min. In contrast, nine studies of patients with impaired liver function had a much longer t1/2 beta (37 h) and a decrease in the rate of total clearance to 48 ml/min. These factors resulted in an increase in the value of area under the concentration-time curve from 59 to 3,434 micrograms X h/ml. These results have demonstrated the importance of the effects of liver function on vancomycin disposition. The vancomycin dose and schedule should be adjusted for patients with liver impairment.
Selection and characterization of beta-lactam-resistant Escherichia coli K-12 mutants
Authors: Jaffé A , Chabbert Y A , Derlot E
Published: June 2012

beta-Lactam-resistant mutants of Escherichia coli K-12 were selected by using 12 different beta-lactam derivatives. The mutants fell into three categories showing (i) altered permeation through reduction or loss of outer membrane porin proteins (including ompF, ompR, and envZ alleles); (ii) increase in the rate of synthesis of chromosomally mediated beta-lactamase; or (iii) defective synthesis or action of cyclic adenosine 3',5'-phosphate (cya and crp alleles).
In vitro antibacterial properties of AT-2266, a new pyridonecarboxylic acid
Authors: Nakamura S , Minami A , Katae H , Inoue S , Yamagishi J , Takase Y , Shimizu M
Published: June 2012

AT-2266, 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-1,8-naphthyridine-3 -carboxylic acid, is a new pyridonecarboxylic acid derivative with broad and potent antibacterial activity. It inhibited some gram-positive bacteria, such as staphylococci and Bacillus subtilis, and most gram-negative bacteria, including Serratia marcescens, Pseudomonas aeruginosa, Haemophilus influenzae, and Campylobacter jejuni, at concentrations of 0.1 to 0.78 microgram/ml, and most gram-positive bacteria, glucose-nonfermenters, and Mycoplasma pneumoniae at concentrations of 1.56 to 12.5 micrograms/ml. Most of the clinical isolates tested were as susceptible to AT-2266 as were laboratory strains. The antibacterial potency of AT-2266 was higher than those of pipemidic acid and nalidixic acid and similar to that of norfloxacin. AT-2266 was not cross-resistant with antibiotics and inhibited most highly nalidixic acid-resistant bacteria at concentrations of 1.56 to 3.13 micrograms/ml. Its activity was barely affected by the addition of horse serum or sodium cholate but weakened by lowering the medium pH or increasing the inoculum size. AT-2266 was bactericidal at concentrations near its minimal inhibitory concentrations. Frequencies of mutants resistant to 10 micrograms of AT-2266 per ml were lower than 4.0 x 10(-9).
In vitro activity of CI-919 (AT-2266), an oral antipseudomonal compound
Authors: Chartrand S A , Scribner R K , Weber A H , Welch D F , Marks M I
Published: June 2012

We tested CI-919 (AT-2266), a nalidixic acid analog, against 555 gram-positive and gram-negative bacteria, using microbroth or agar dilution methods. The activity of CI-919 was compared with those of cephalosporins, tobramycin, ticarcillin, dicloxacillin, rifampin, chloramphenicol, ampicillin, and trimethoprimsulfamethoxazole. The minimal inhibitory concentrations of CI-919 for 90% of isolates were (in micrograms per milliliter): Pseudomonas spp. (including Pseudomonas aeruginosa), 4.0; Enterobacteriaceae, 0.5; Staphylococcus spp., 2.0; Haemophilus influenzae, 0.12; Campylobacter jejuni, 0.12; and enterococci, 16. The minimal inhibitory concentrations of CI-919 for 90% of 82 tobramycin-resistant, gram-negative strains was 4.0 micrograms/ml. CI-919 was bactericidal for most isolates, showing no cross-resistance with unrelated antimicrobial agents, and was stable for 11 weeks at temperatures ranging from 22 to -70 degrees C. Inoculum size and media pH had little effect on the antibacterial activity of CI-919 for nine strains tested. CI-919 may be useful as an oral antibiotic for the treatment of infections due to diverse bacteria, including P. aeruginosa.
Vancomycin pharmacokinetics in patients with peritonitis on peritoneal dialysis
Authors: Magera B E , Arroyo J C , Rosansky S J , Postic B
Published: June 2012

Vancomycin pharmacokinetics were studied in four patients with peritonitis undergoing chronic intermittent peritoneal dialysis. Serum levels exceeding 4.0 micrograms/ml were maintained for 8 and 13 days after a single 1-g intravenous dose. Vancomycin serum concentrations measured before, during, and upon completion of dialysis revealed no appreciable decline. Peritoneal fluid concentrations in two patients exceeded 4.0 micrograms/ml for more than 12 days.
Sequence homology of clindamycin resistance determinants in clinical isolates of Bacteroides spp
Authors: Marsh P K , Malamy M H , Shimell M J , Tally F P
Published: June 2012

The sequence homology of clindamycin resistance (Clnr) determinants was studied in 16 Clnr Bacteroides strains. The isolates were surveyed for plasmid content, homology with the Clnr determinant of pBFTM10, and ability to transfer Clnr. The Clnr DNA probes used in the Southern hybridizations were pBFTM10 and a plasmid derivative containing an EcoRI fragment of pBFTM10 cloned into Escherichia coli. A total of 13 of 16 Clnr strains also carried tetracycline resistance, and 15 of 16 Clnr Bacteroides isolates showed homology with the Clnr determinant of pBFTM10. These data suggest that the previously characterized Clnr determinant of pBFTM10 is widely distributed in nature and may be found on either a plasmid or the chromosome. The Clnr Bacteroides fragilis strain which lacked homology with pBFTM10 also had different transfer properties; thus, more than one type of Clnr determinant may exist in Bacteroides spp.
Effects of mecillinam and cefoxitin on growth, macromolecular synthesis, and penicillin-binding proteins in a variety of streptococci
Authors: McDowell T D , Buchanan C E , Coyette J , Swavely T S , Shockman G D
Published: June 2012

Although some strains of streptococci seem to be virtually inert to mecillinam, the growth of other strains, notably certain viridans streptococci (Streptococcus mutans and Streptococcus sanguis) was inhibited by relatively low concentrations of the drug. Inhibition of the synthesis of peptidoglycan, RNA, protein, and DNA in two tolerant strains, S. mutans FA-1 and GS-5, was studied over a wide range of concentrations of mecillinam, benzylpenicillin, and cefoxitin. The responses of both strains to all three beta-lactams were very similar; that is, synthesis of insoluble peptidoglycan was most susceptible. Inhibition of peptidoglycan synthesis was followed rapidly and sequentially by substantial but less severe inhibitions of RNA and protein synthesis. Significant inhibition of DNA synthesis was not observed. Binding studies with [14C]benzylpenicillin alone or after preexposure of membrane preparations to benzylpenicillin, mecillinam, or cefoxitin suggest that reasonably selective binding of a beta-lactam antibiotic to one or two of the major penicillin-binding proteins (PBP 1 or PBP 4) of S. mutans GS-5 and FA-1 may be the initial step in the series of events that results in the inhibition of growth and in the inhibition of insoluble peptidoglycan assembly and of RNA and protein synthesis.
Transferable Resistance to Clindamycin, Erythromycin, and Tetracycline in
Clostridium difficile
Authors: Wüst Jürg , Hardegger Ursula
Published: June 2012

Resistance to clindamycin, erythromycin, and streptogramins in
Clostridium difficile
could be transferred to a susceptible strain by mixed culture at low frequencies (1 × 10
−8
to 4 − 10
−8
per donor cell). Transfer of tetracycline resistance occurred at frequencies of 3 × 10
−7
to 5 × 10
−7
. No plasmid DNA involved in these transfers could be detected.
Cefonicid concentrations in serum and atrial tissue during open-heart surgery
Authors: Sterling R P , Connor D J , Norman J C , Cooley D A
Published: June 2012

Cefonicid was administered intramuscularly 1 h before open-heart surgery to seven patients in doses of 1 g each and to six patients in doses of 2 g each. Cefonicid concentrations were measured in the right atrial biopsy and in serum at onset of surgery, at time of atrial biopsy, 15 min after starting cardiopulmonary bypass, and at completion of cardiopulmonary bypass. Concentrations in the atrial biopsy and in serum at all periods exceeded the minimal inhibitory concentrations for organisms most frequently responsible for postoperative infections.
Enterococci from Bangkok, Thailand, with high-level resistance to currently available aminoglycosides
Authors: Murray B E , Tsao J , Panida J
Published: June 2012

Enterococcal endocarditis is usually treated with a combination of a penicillin and an aminoglycoside. Recent reports have documented the emergence of enterococci in France with high-level resistance to gentamicin, tobramycin, and kanamycin and the emergence of strains in Houston, Tex. with high-level resistance to all of these drugs and streptomycin. In this study, we examined strains from a geographic area where newer aminoglycosides have been less commonly used. Of 125 distinct patient isolates, 18 (14%) were resistant to greater than 2,000 micrograms of gentamicin and most other aminoglycosides per ml. Four of these strains transferred gentamicin resistance to a laboratory recipient. One strain, chosen for further study, was resistant to synergism between penicillin and gentamicin, tobramycin, kanamycin, streptomycin, and amikacin and demonstrated the following enzymatic activities: 3'- and 2"-aminoglycoside phosphotransferases, 6'-aminoglycoside acetyltransferase, and adenylylation of streptomycin. Optimal therapy for endocarditis caused by such highly resistant strains is currently unknown.
Pharmacokinetics and tissue penetration of ticarcillin combined with clavulanic acid
Authors: Bennett S , Wise R , Weston D , Dent J
Published: June 2012

A combination of 3 g of ticarcillin and 200 mg of clavulanic acid was administered intravenously to six healthy male volunteers, after which the concentrations of these agents in serum and blister fluid were measured. The ratio of the two drugs in serum varied from 15:1 (ticarcillin-clavulanic acid) at the time of administration to 28:1 at 30 min and 62:1 at 5 h after injection. Both agents penetrated blister fluid rapidly, the ratio being 33:1 at 1 h and 66:1 at 3 h. The elimination rates of these agents were different, but for each compound they were similar in serum and blister fluid.
Pharmacokinetics of cefoperazone in full-term and premature neonates
Authors: Rosenfeld W N , Evans H E , Batheja R , Jhaveri R C , Vohra K , Khan A J
Published: June 2012

The pharmacokinetics of cefoperazone were evaluated in 28 newborn infants who were being treated for sepsis. A dose of 50 mg/kg was administered intravenously on days 0 to 2 in all, with a second dose administered on days 5 to 7 in 14 infants. Cerebrospinal fluid penetration was also studied in seven neonates. The mean peak concentration of cefoperazone in the serum of premature infants less than 33 weeks of gestational age, 159 (standard deviation, +/- 22) micrograms/ml, was higher than concentrations in premature infants 33 to 36 weeks of age and full-term infants (110 +/- 41 and 109 +/- 29 micrograms/ml, respectively). The mean concentrations 24 h after dosage were similar in all three groups, 13 to 17 micrograms/ml. The mean serum half-lives were similar in the three subgroups and ranged from 7 to 9 h. After the dose at 5 to 7 days, mean blood levels in the subgroups at 0.5 h were 149, 112, and 112 micrograms/ml; 24-h levels ranged from 9 to 12 micrograms/ml. The mean serum half-lives ranged from 5 to 7 h. Cerebrospinal fluid levels in patients with meningitis ranged from 2.8 to 9.5 micrograms/ml and in patients without meningitis from 1 to 7 micrograms/ml. Peak blood levels were 15 to 1,000 times higher than the 90% minimal inhibitory concentration of common pathogens found in newborns. These observations support the potential efficacy of cefoperazone in treatment of infections, including meningitis, in newborn infants.