bluuebunny/crossref_metadata_2025 huggingface dataset:
Conjugative transfer of staphylococcal antibiotic resistance markers in the absence of detectable plasmid DNA
Authors: el Solh N , Allignet J , Bismuth R , Buret B , Fouace J M
Published: June 2012

Eleven Staphylococcus aureus clinical isolates were tested for transfer of resistance markers by transduction and filter mating. The resistance markers of six of the strains could be transferred only by transduction; however, the five remaining strains transferred their resistance both by transduction and filter mating. The resistance markers that were cotransferred in filter matings (transfer of resistance to penicillin and streptogramin A was accompanied, in each case, by the transfer of one or more markers, i.e., resistance to aminoglycosides, cadmium, or tetracycline, depending on the donor) were not cotransduced. The filter mating transfers were recA independent and were observed with both Staphylococcus aureus and Staphylococcus epidermidis recipients. Experiments to elucidate the mechanism of transfer by filter mating suggested that conjugation requiring cell-to-cell contact may have been involved. These transfers occurred in the absence of detectable plasmid DNA.
Frequency of aminoglycoside 6'-N-acetyltransferase among Serratia species during increased use of amikacin in the hospital
Authors: Larson T A , Garrett C R , Gerding D N
Published: June 2012

The incidence of tobramycin-resistant, gentamicin-susceptible Serratia species at the Minneapolis Veterans Administration Medical Center decreased from an average 42.1 to 2.5% (P less than 0.001) during a 4.5-year period despite the predominant use of amikacin. These organisms were shown to express a 6'-N-acetyltransferase-modifying enzyme (EC 2.3.1.82). Resistance was not shown to be plasmid mediated.
Comparative in vitro activity of imipenem against Haemophilus influenzae and Haemophilus parainfluenzae
Authors: Cerami A T , Shungu D L
Published: June 2012

A microdilution broth method was used to test 77 clinical isolates of Haemophilus influenzae and Haemophilus parainfluenzae, including beta-lactamase-positive and -negative strains, for susceptibility to ampicillin, chloramphenicol, and imipenem. Except for ampicillin against beta-lactamase-producing strains (MIC for 90% of strains [MIC90], greater than or equal to 128 micrograms/ml), all three antimicrobial agents had comparable in vitro activity (MIC90, less than or equal to 1 microgram/ml) against these bacterial strains.
Activity of inosine analogs against Pneumocystis carinii in culture
Authors: Bartlett M S , Marr J J , Queener S F , Klein R S , Smith J W
Published: June 2012

Three analogs of inosine, formycin B, allopurinol ribonucleoside, and 9-deazainosine, were tested for their ability to suppress proliferation of Pneumocystis carinii in culture with WI-38 cells. The organism was inhibited by 9-deazainosine at 10 micrograms/ml, and there was some inhibition at 1 microgram/ml. Formycin B was effective only at 40 micrograms/ml. Allopurinol ribonucleoside had little effect.
Vancomycin enhancement of experimental tobramycin nephrotoxicity
Authors: Wood C A , Kohlhepp S J , Kohnen P W , Houghton D C , Gilbert D N
Published: June 2012

The influence of vancomycin on tobramycin nephrotoxicity was assessed in male Fischer rats. Treatment groups included controls receiving diluent and groups receiving vancomycin alone at a dosage of 200 mg/kg (body weight) per day, tobramycin alone at a dosage of 80 mg/kg per day, and a combination of vancomycin and tobramycin at the above dosages. All regimens were injected on a twice-a-day schedule. The animals were sacrificed on days 1, 3, 10, 14, 17, and 21. When compared with controls, animals receiving vancomycin alone exhibited no detectable renal toxicity. Compared with the case with controls, tobramycin alone was toxic, as manifested by lower mean animal weights, increased blood urea nitrogen concentrations on days 14 and 17 (P less than 0.005), increased serum creatinine concentrations on days 17 and 21 (P less than 0.005), and the presence of renal cortical tubular necrosis and regeneration. When compared with tobramycin alone, the combination of vancomycin and tobramycin caused earlier and more severe toxicity. By day 10, the magnitude of weight loss, the rise in blood urea nitrogen, and the increase in serum creatinine concentration were all greater in the rats given the combination of vancomycin plus tobramycin than in the animals given tobramycin alone (P less than 0.005). In addition, there was more proximal tubular necrosis and regeneration in rats given vancomycin plus tobramycin compared with those given tobramycin alone. In this animal model, vancomycin alone caused no detectable renal injury, tobramycin alone produced minimal proximal tubular damage, and the combination of vancomycin and tobramycin resulted in a greater degree of kidney injury than observed with tobramycin alone.
In vitro activity of piperacillin, ticarcillin, and mezlocillin alone and in combination with aminoglycosides against Pseudomonas aeruginosa
Authors: Lyon M D , Smith K R , Saag M S , Cloud G A , Cobbs C G
Published: June 2012

A total of 103 isolates of Pseudomonas aeruginosa were studied to compare the in vitro effectiveness of three beta-lactam antibiotics (piperacillin, ticarcillin, and mezlocillin) when used alone and in combination with four aminoglycosides (tobramycin, gentamicin, amikacin, and netilmicin). All drugs were tested as single agents against a standard inoculum (5 X 10(5) CFU/ml). The three antipseudomonal penicillins were also tested against the isolates at a higher inoculum concentration (10(7) CFU/ml). Synergy testing was performed by the two-dimensional checkerboard method and was defined by a fractional bactericidal index of less than or equal to 0.5 and bacterial killing accomplished at antibiotic concentrations no greater than those achievable in serum. All combinations were assessed for synergy. The degree of synergy was further analyzed by dividing the isolates into groups based on their susceptibility and resistance to the individual agents in the combination. The overall effectiveness of the various aminoglycoside-antipseudomonal penicillin combinations was assessed regarding their ability to kill the isolates either as single agents or through synergy. Piperacillin was the most active antipseudomonal penicillin, and tobramycin and amikacin were the most active aminoglycosides when used as single agents. When tested against isolates at a higher inoculum concentration, ticarcillin was significantly more active than the other beta-lactams. The highest degree of overall synergy was noted with gentamicin-ticarcillin (78.2% of strains) and amikacin-piperacillin (77% of strains). When assessed for overall effectiveness, all combinations containing amikacin were the most active. The combination of amikacin-piperacillin was the most effective, with activity against 96% of all isolates.
Antirhinovirus compound 44,081 R.P. inhibits virus uncoating
Authors: Alarcon B , Zerial A , Dupiol C , Carrasco L
Published: June 2012

44,081 R.P., or 2-[(1,5,10,10a-tetrahydro-3H-thiazolo[3,4-b]isoquinolin- 3-ylidine)amino]-4-thiazole acetic acid, is a compound which selectively inhibits rhinovirus in cell cultures. The compound, which was unable to inactivate infectivity of virions, appeared to act prior to RNA and protein synthesis without affecting adsorption or penetration of virus in MRC5 cells. In contrast, it protected intracellular [5-3H]uridine-labeled virions against the effects of RNase treatment, indicating that inhibition of virus uncoating is the mode of action of 44 081 R.P.
Alterations in kinetic properties of penicillin-binding proteins of penicillin-resistant Streptococcus pneumoniae
Authors: Handwerger S , Tomasz A
Published: June 2012

Earlier studies have shown that the highly penicillin-resistant South African Strains of pneumococci contain altered penicillin-binding proteins (PBPs) (S. Zighelboim and A. Tomasz, Antimicrob. Agents Chemother. 17:434-442, 1980). We now describe a detailed quantitative characterization of the reaction of radioactively labeled penicillin with the PBPs of the penicillin-susceptible and penicillin-resistant pneumococci and several intermediate-resistance-level genetic transformants as well. The altered binding of the antibiotic by the PBPs of resistant cells appears to be due to a combination of two factors: lower drug affinity and change in the cellular amounts of PBPs. No alteration in the rates of deacylation of the penicilloyl-PBPs of the resistant cells was detected.
Lincomycin stimulates synthesis of TEM-2 beta-lactamase by Escherichia coli
Authors: Okabe A , Matsushita O , Katayama S , Hayashi H
Published: June 2012

Lincomycin increased the TEM-2 beta-lactamase activity of Escherichia coli K-12 cells carrying plasmid RP4 at a concentration which slightly inhibited cell growth. In a control culture beta-lactamase activity reached its maximal level in late log phase, whereas when lincomycin was present beta-lactamase activity continued to increase into the stationary phase. Lincomycin (100 micrograms/ml) inhibited both cell growth and protein synthesis by about 35% but stimulated beta-lactamase activity 2.5-fold per ml of culture and about 4-fold per cell after 20 h of growth. The amount of beta-lactamase produced in each culture was also compared by densitophotometry of a stained sodium dodecyl sulfate-polyacrylamide gel. The relative values were in good agreement with the relative enzyme activities, indicating that the stimulatory effect of lincomycin was due to an increase in the amount of beta-lactamase protein. Inactivation of beta-lactamase appeared to be faster when lincomycin was present. This was determined by measuring the decrease in beta-lactamase activity when phenethyl alcohol was present to prevent maturation of the enzyme. There was no significant difference in plasmid copy number between the cells grown in the presence or absence of lincomycin. These results indicate that lincomycin stimulates transcription, translation, or translocation of beta-lactamase.
High-pressure liquid chromatographic assay of sulbactam in plasma, urine, and tissue
Authors: Bawdon R E , Madsen P O
Published: June 2012

A reverse-phase high-pressure liquid chromatography method for the quantitation of sulbactam in plasma, urine, and tissue is described. The assay used the formation of an imidazole derivative followed by extraction with acetonitrile and dichloromethane and used UV absorbance for detection. The mobile phase consisted of acetonitrile, tetrabutylammonium hydroxide, and phosphate buffer. The assay was linear from 100 micrograms/ml (g of tissue) to 1 microgram/ml (g). Within- and between-batch recovery was greater than 90%. The coefficient of variation was generally less than 15%. There were no interfering peaks in the quantitation of sulbactam.
Isolation and characterization of norfloxacin-resistant mutants of Escherichia coli K-12
Authors: Hirai K , Aoyama H , Suzue S , Irikura T , Iyobe S , Mitsuhashi S
Published: June 2012

We isolated spontaneous mutants from Escherichia coli K-12 with low-level resistance to norfloxacin. These mutants were classified into the following three types on the basis of their properties: (i) NorA appeared to result for mutation in the gyrA locus for the A subunit of DNA gyrase; (ii) NorB showed low-level resistance to quinolones and other antimicrobial agents (e.g., cefoxitin, chloramphenicol, and tetracycline), and the norB gene was considered to map at about 34 min on the E. coli K-12 chromosome; (iii) NorC was less susceptible to norfloxacin and ciprofloxacin but was hypersusceptible to hydrophobic quinolones such as nalidixic acid and rosoxacin, hydrophobic antibiotics, dyes, and detergents. Susceptibility to bacteriophages and the hydrophobicity of the NorC cell surface also differed from that of the parent strain. The norC gene was located near the lac locus at 8 min on the E. coli K-12 chromosome. Both NorB and NorC mutants had a lower rate of norfloxacin uptake, and it was found that the NorB mutant was altered in OmpF porin and that the NorC mutant was altered in both OmpF porin and apparently in the lipopolysaccharide structure of the outer membrane.
Activity of roxithromycin (RU 28965), a macrolide, against Toxoplasma gondii infection in mice
Authors: Chan J , Luft B J
Published: June 2012

Roxithromycin (RU 28965), an ether oxime derivative of erythromycin, protected mice against a lethal infection with the virulent RH strain of Toxoplasma gondii. Therapy begun 24 h before, 2 h after, and 24 h after infection with 2 X 10(3) tachyzoites protected 90, 80, and 50% of the mice, compared with 0% of untreated controls (P less than 0.05 to 0.001). Toxoplasma was isolated in less than 20% of surviving roxithromycin-treated mice.
Determination of norfloxacin and ciprofloxacin concentrations in serum and urine by high-pressure liquid chromatography
Authors: Morton S J , Shull V H , Dick J D
Published: June 2012

A high-pressure liquid chromatographic method for the determination of norfloxacin or ciprofloxacin concentrations in body fluids was developed and compared with a standard bioassay. The high-pressure liquid chromatographic assay utilizes a reverse-phase C18 column, an internal standard, and fluorescence detection, with reproducibility studies yielding coefficients of variation ranging from 0.6 to 3.7% and 0.9 to 2.7% for norfloxacin and ciprofloxacin, respectively. Correlation coefficients with the bioassay were 0.966 for norfloxacin and 0.952 for ciprofloxacin.
Effect of antibiotics on adherence of Haemophilus influenzae type b
Authors: Gilsdorf J R , Jesperson J M
Published: June 2012

During antibiotic therapy for serious Haemophilus influenzae type b infections in children, respiratory mucosal colonization with this organism is suppressed but not eradicated. To define possible mechanisms contributing to this suppression, the ability of six antibiotics to influence the adherence of H. influenzae type b to human epithelial cells was investigated. In assays in which the organisms were grown in broth containing 0.5 X the MIC of rifampin, ampicillin, clindamycin, chloramphenicol, lincomycin, or trimethoprim-sulfamethoxazole, all drugs except rifampin significantly reduced bacterial adherence. In assays in which nonreplicating organisms were exposed to the antibiotics, all six drugs reduced the adherence of the bacteria. In assays in which the epithelial cells were exposed to the antibiotics, all drugs reduced bacterial adherence. In addition, the presence of ampicillin, chloramphenicol, lincomycin, or trimethoprim-sulfamethoxazole appeared to facilitate the release of organisms adherent to epithelial cells. Thus, antibiotics appear to inhibit adherence of H. influenzae type b to human epithelial cells and may interfere with bacterial or epithelial cell binding sites. These observations may explain the suppression of H. influenzae type b mucosal colonization that occurs during antibiotic treatment of patients with systemic H. influenzae type b infections.
Renal cortical kinetics of gentamicin after implantation of gentamicin-polymethylmethacrylate beads in rats
Authors: Giuliano R A , Verpooten G A , De Broe M E
Published: June 2012

Beads of gentamicin-polymethylmethacrylate (Septopal), each containing 4.5 mg of gentamicin base, were implanted intraperitoneally in rats. Each rat received one bead. Serum levels and urinary excretion of gentamicin were maximal in the first day of treatment (0.6 micrograms/ml in serum 3 h after implantation of the bead and 525 micrograms per 24-h urine sample) and decreased thereafter. Kidney cortical concentrations of gentamicin progressively increased and peaked after 4 days, reaching 117 micrograms/g. Tissue levels decreased thereafter in spite of the persistence of the drug in urine, and this occurred in the absence of cell damage leading to cell death. Release of gentamicin from intact proximal tubular cells, despite continuous uptake, prevented intracellular drug concentrations from reaching a nephrotoxic level. This experimental study provides a rational basis for the previous clinical observation that nephrotoxicity due to treatment with gentamicin-polymethylmethacrylate beads is improbable.
Membrane perturbation by aminoglycosides as a simple screen of their toxicity
Authors: Au S , Weiner N , Schacht J
Published: June 2012

A simple test to assess the toxicity of aminoglycosides was designed based on the interaction of these drugs with phosphatidylinositol bisphosphate. The fluorescent probe 1-anilino-8-naphthalene sulfonate was incorporated into liposomes composed of L-alpha-phosphatidylcholine and phosphatidylinositol bisphosphate (4:1 molar ratio), and changes in fluorescence induced by the aminoglycosides were measured. The magnitude of these changes correlated well with the intrinsic ototoxicity of the drugs previously established in cochlear perfusions: neomycin greater than gentamicin approximately equal to tobramycin greater than amikacin approximately equal to kanamycin approximately equal to netilmicin greater than neamine approximately equal to spectinomycin. Correlations were not accurate when other phospholipids were substituted for phosphatidylinositol bisphosphate. An alternative in vitro test, measurement of the zeta potential of liposomes, ranked the drugs according to their electrostatic charge but not their toxicity. These results suggest that: a simple screen for aminoglycoside toxicity can be established and perturbation of membranes containing phosphatidylinositol bisphosphate is a key step in aminoglycoside ototoxicity.
7 alpha-formylamino substituent confers beta-lactamase-inactivating potency on 1-oxacephalosporins
Authors: Murakami K , Doi M , Yoshida T
Published: June 2012

7 alpha-Formylamino-1-oxacephalosporins 7 alpha-formylamino-7 beta-[2- (methylaminocarbonyl)amino-2-(2-thienyl)acetamido]-3-[(1-methyl-1H -tetra zol-5-yl)thiomethyl]-1-oxa-3-cephem-4-carboxylic acid (F1) and 7 alpha-formylamino-7 beta-(2-[(4-ethyl-2,3-dioxopiperazine-1- yl)carbonylamino]-2-phenylacetamido)-3-[(1-methyl-1H-tetr azol-5-yl) thiomethyl]-1-oxa-3-cephem-4-carboxylic acid (F2) were stable against penicillinases and, moreover, inactivated cephalosporinases of Pseudomonas aeruginosa, Citrobacter freundii, and Enterobacter cloacae. Extensive studies of the inactivation of cephalosporinase of P. aeruginosa showed that it resulted from the formation of a transiently stable enzyme-compound complex. The 7 alpha-formylamino substituent was involved in the enzyme inactivation, because 7 alpha-methoxy congeners did not inactivate the enzyme. The number of compound molecules required for inhibition of an enzyme molecule was found to be 36 for F1 and 5.5 for F2, which suggests that the pathway to the complex formation branched off the hydrolysis pathway. Half-lives of the complexes were 400 min for F1 and 260 min for F2. 7 alpha-Formylamino compounds F1 and F2 had antibacterial activities similar to those of 7 alpha-methoxy congeners against beta-lactamase-producing gram-negative bacteria, whereas they were less active against non-beta-lactamase-producing strains of Escherichia coli and Staphylococcus aureus. The conclusion was that the 7 alpha-formylamino substituent conferred the ability to inactivate cephalosporinase on the 1-oxacephalosporins tested, without much impairment of their antibacterial activity.
Influence of beta-lactam antibiotics and ciprofloxacin on composition and immunogenicity of Escherichia coli outer membrane
Authors: Leying H , Suerbaum S , Kroll H P , Karch H , Opferkuch W
Published: June 2012

The effects of subinhibitory concentrations of different beta-lactam antibiotics and one quinolone on the sedimentation of outer membranes (OMs) of Escherichia coli and on the qualitative properties and immunogenicity of OM components were studied. Membranes were prepared by osmotic lysis of plasmolyzed bacteria. OM and cytoplasmic membrane vesicles were separated by sucrose density ultracentrifugation. Two peaks of OM vesicles with different buoyant densities could be isolated; the quantitative contribution of these to the total OM varied, depending upon the growth phase. In early log phase, the OM consisted mainly of lighter material; in late log and stationary phases, the OM consisted mainly of heavier material. Moxalactam, imipenem, and ciprofloxacin inhibited the formation of heavier material in all growth phases. The immunogenicity of OM vesicles was tested in mice by the hemolytic plaque test. The lighter OM material was markedly less immunogenic than the heavier OM material. The vesicles from antibiotic-treated bacteria and those from early-log-phase cells were less immunogenic than vesicles from untreated late-log-phase and stationary-phase bacteria. These changes were found for the immune response against lipopolysaccharides, as well as against OM proteins. Thus, the immunogenicity of OM components seems to be dependent upon the quantitative composition of lighter and heavier compounds, which is strongly influenced by growth phase and treatment with certain antibiotics.
Delayed treatment with combinations of antiviral drugs in mice infected with herpes simplex virus and application of the median effect method of analysis
Authors: Schinazi R F , Chou T C , Scott R T , Yao X J , Nahmias A J
Published: June 2012

Mice were inoculated intracerebrally with a lethal dose of herpes simplex virus type 2. Three days later, the mice were treated intraperitoneally, twice daily for 4 days, with the following drugs alone or in combination: acyclovir (ACV), vidarabine (ara-A), 2'-fluoro-5-iodoaracytosine (FIAC), and 2'-fluoro-5-methylarauracil (FMAU). Despite delayed treatment, most of the animals receiving low doses of FMAU alone or in combination with ACV or ara-A survived. In contrast, significantly higher mortality rates were noted in mice receiving ara-A, ACV, or FIAC alone. The data were analyzed for quantitation of synergism, additivity, and antagonism of multiple drug effect by the median effect method. The median effective doses (in nanomoles per kilogram per day) calculated in this manner were: FMAU, 22.5; FIAC, 510; ara-A, 901; ACV, 7,587; ACV-ara-A (drug ratio, 1:1), 550; FIAC-ara-A (1:1), 376; FIAC-ACV (1:1), 133; FMAU-ACV (1:8), 60.3; and FMAU-ara-A (1:8), 65.2. Marked synergy was found throughout a wide range of effect levels with the five different combinations, with no increased toxicity over the single-drug treatments. Similar results were obtained when the data were analyzed by the isobologram method. Since many patients with severe herpetic infections, such as herpes encephalitis, have a poor prognosis despite single-drug therapy, the possible use of combinations including low doses of FMAU deserves further investigation.
Allium sativum (garlic) inhibits lipid synthesis by Candida albicans
Authors: Adetumbi M , Javor G T , Lau B H
Published: June 2012

The effect of aqueous garlic extract on the macromolecular synthesis of Candida albicans was studied. Protein and nucleic acid syntheses were inhibited to the same extent as growth, but lipid synthesis was completely arrested. Blockage of lipid synthesis is likely an important component of the anticandidal activity of garlic.
Norfloxacin in the therapy of uncomplicated gonorrhea
Authors: Romanowski B , Wood H , Draker J , Tsianco M C
Published: June 2012

In an open study, 70 patients with uncomplicated anogenital Neisseria gonorrhoeae infection were evaluated to determine the efficacy and safety of a single oral dose of norfloxacin (800 mg). Norfloxacin cured all 31 male urethral and 25 endocervical infections. All 63 isolates of N. gonorrhoeae tested were inhibited by 0.05 microgram of norfloxacin per ml.
Effect of clavulanic acid on the activity of ticarcillin against Pseudomonas aeruginosa
Authors: Tausk F , Stratton C W
Published: June 2012

We studied the ability of clavulanic acid (CA) to induce beta-lactamase in Pseudomonas aeruginosa isolates and what effect this might have on the susceptibilities to beta-lactam agents. We first used a disk approximation method to test 4 laboratory and 16 clinical P. aeruginosa isolates against antipseudomonal beta-lactam agents for truncation by CA and found this to be very common. All antimicrobial compounds except imipenem demonstrated truncation in the vicinity of CA. We also evaluated the extent to which chromosomal beta-lactamase is induced by CA and found this to occur to some degree in most isolates and to be dependent on the concentration of CA. Finally, we performed time kill curves on these isolates to compare bacterial growth in ticarcillin alone with growth in ticarcillin-CA (the CA at 2 or 4 micrograms/ml). We found that CA at this concentration has neither an antagonistic nor a synergistic antibacterial effect in combination with ticarcillin.
Failure of norfloxacin to eradicate Chlamydia trachomatis in nongonococcal urethritis
Authors: Bowie W R , Willetts V , Sibau L
Published: June 2012

Norfloxacin has some activity in vitro against Chlamydia trachomatis and Ureaplasma urealyticum, although not at levels attainable in serum. In this study, norfloxacin was administered (400 mg orally twice daily for 10 days) to men with acute nongonococcal urethritis. Of 25 men from whom C. trachomatis was initially isolated, 21 had the organism reisolated at the first follow-up visit posttreatment, and there were minimal changes in the number of inclusion-forming units in culture. Ultimately, all but 1 of the 22 men from whom C. trachomatis was initially isolated and who were monitored became clinical failures within 42 +/- 7 days posttreatment. The clinical outcome was significantly better for men from whom U. urealyticum was initially isolated but from whom C. trachomatis was not isolated. Of 27 men, 17 became and stayed culture negative for U. urealyticum at follow-ups, and clinically, 15 no longer had nongonococcal urethritis. Of these 15, all 12 monitored until at least 42 +/- 7 days posttreatment remained improved. Of 26 men from whom neither C. trachomatis nor U. urealyticum was initially isolated, 18 improved and all 15 who were monitored until at least 42 +/- 7 days posttreatment remained improved. Thus, although norfloxacin attains high levels in urine and has good tissue penetration, it had essentially no activity against chlamydial urethritis in men. It had better, but incomplete, activity against U. urealyticum. For quinolones to show promise in vivo against C. trachomatis, either the MICs will need to be much lower or the levels attained in serum will have to be much higher.
Antibiotic resistance patterns of Vibrio mimicus isolated from human and environmental sources in Bangladesh
Authors: Chowdhury M A , Aziz K M , Rahim Z , Kay B A
Published: June 2012

Twenty-five environmental and 19 clinical strains of Vibrio mimicus were tested for antibiotic susceptibility patterns. Environmental strains were resistant to streptomycin, kanamycin, and trimethoprim-sulfamethoxazole; clinical strains were susceptible. Environmental strains showed variable resistance to ampicillin (44%), but clinical strains were susceptible. All strains tested were susceptible to chloramphenicol and gentamicin.
Comparison of susceptibility of gentamicin-resistant and -susceptible "Acinetobacter anitratus" to 15 alternative antibiotics
Authors: Stiver H G , Bartlett K H , Chow A W
Published: June 2012

Fifty-four clinical isolates of "Acinetobacter anitratus" separated cleanly into gentamicin-susceptible (16 strains) and gentamicin-resistant (38 strains) subpopulations. When tested with a 10(4)-CFU inoculum, gentamicin resistance was associated with a greater than fourfold increase in the MICs of norfloxacin, ciprofloxacin, A-56620, tobramycin, and amikacin for 50% of the strains. Antimicrobial agents with MICs for 90% of gentamicin-resistant strains in the susceptible range were ciprofloxacin, A-56619, A-56620, imipenem, SCH-34343, ceftazidime, aztreonam, carbenicillin, ticarcillin, and piperacillin. These agents may be useful alternative drugs for treating infections caused by aminoglycoside-susceptible and -resistant "A. anitratus."
Frequency of four classes of tetracycline resistance determinants in Salmonella and Shigella spp. clinical isolates
Authors: Martínez-Salazar J M , Alvarez G , Gómez-Eichelmann M C
Published: June 2012

The frequencies of tetracycline resistance determinants of the classes A, B, C, and D were determined in 53 non-lactose-fermenting clinical isolates. The most frequent class of determinant in Salmonella typhimurium and Shigella flexneri strains was class B; however, the predominant determinant in Shigella sonnei strains was class C.
Genetic analysis and penicillin-binding protein alterations in Neisseria gonorrhoeae with chromosomally mediated resistance
Authors: Dougherty T J
Published: June 2012

Eight recent isolates of Neisseria gonorrhoeae with high-level non-beta-lactamase-mediated penicillin resistance were investigated. The penicillin-binding proteins of these strains were found to have reduced affinity for radiolabeled penicillin. Testing for known resistance genes showed that these were present in the resistant isolates. Genetic transformation was used to construct strains with increasing levels of antibiotic resistance. Modification of the transformation protocol made it possible to isolate transformants at the highest (penicillin-resistant DNA donor) level of resistance. These transformants unexpectedly yielded two distinct penicillin-binding protein patterns when tested.
Novel mechanism for plasmid-mediated erythromycin resistance by pNE24 from Staphylococcus epidermidis
Authors: Lampson B C , von David W , Parisi J T
Published: June 2012

We describe an unusual type of erythromycin resistance (Emr) mediated by a plasmid designated pNE24 from Staphylococcus epidermidis. This 26.5-kilobase plasmid encodes resistance strictly to 14-membered macrolide antibiotics, erythromycin, and oleandomycin. Resistance to other macrolide-lincosamide-streptogramin B (MLS) antibiotics was not observed even after a prior induction stimulus with various MLS antibiotics. Plasmid pNE24 was found to express resistance constitutively and manifested a low to intermediate MIC (62.5 micrograms/ml) for erythromycin. The resistance gene, designated erpA, appears to mediate resistance by altering the permeability of the host cell for erythromycin, because the measured uptake of 14C-labeled erythromycin by strain 958-2 (containing pNE24) was lower than for the erythromycin-susceptible, isogenic strain 958-1. No inactivation of erythromycin in overnight broth culture supernatants could be detected. In addition, no significant loss in binding affinity between [14C]erythromycin and ribosome could be detected for ribosomes isolated from strain 958-2 relative to 958-1, indicating that pNE24 probably does not produce a modification of the bacterial ribosome. No other selectable marker was found associated with pNE24; however, a 60,000-dalton protein was present only in the membrane fractions of cells (958-2) containing pNE24 and may play a role in mediating resistance to erythromycin.
Modulation of bacteriolysis by cooperative effects of penicillin-binding proteins 1a and 3 in Escherichia coli
Authors: Tuomanen E , Gilbert K , Tomasz A
Published: June 2012

Escherichia coli characteristically lyses upon treatment with most beta-lactam antimicrobial agents. In contrast, an investigational aminothiazole cephem, CGP 31523A, produced a new combination of antibacterial effects: it was highly bactericidal without causing cell wall degradation or lysis. Killing was associated with the formation of vacuolated filaments. Because the compound bound to penicillin-binding proteins (PBPs) 1a and 3, we investigated the role of PBP 3 in modulation of lysis caused by inhibition of PBP 1a. A temperature-sensitive mutant with a nonfunctional PBP 3 lysed when treated with CGP 31523A. The combination of a PBP 1 inhibitor (cefsulodin) and a PBP 3 inhibitor (aztreonam) also caused filamentation and death without lysis of wild-type cells over a narrow concentration range. We conclude that cooperative effects between PBPs in E. coli can lead to a dissociation of bacterial killing and lysis.
Penetration of aztreonam into cerebrospinal fluid and brain of noninfected rabbits and rabbits with experimental meningitis caused by Pseudomonas aeruginosa
Authors: Strausbaugh L J , Bodem C R , Laun P R
Published: June 2012

This study examined the penetration of aztreonam into the cerebrospinal fluid (CSF) and brain in noninfected rabbits and rabbits with experimental meningitis caused by Pseudomonas aeruginosa. Animals received either 600 or 1,200 mg of aztreonam administered intravenously over 6 h. Aztreonam did not readily enter the CSF in the absence of meningitis. In noninfected animals, mean concentrations in the CSF ranged from 1.1 to 3.0 micrograms/ml with the 600-mg dose and from 2.3 to 4.7 micrograms/ml with the 1,200-mg dose. In contrast, mean concentrations of aztreonam in the CSF were significantly higher (P less than 0.01) at each sampling time in rabbits with experimental meningitis caused by P. aeruginosa. They ranged from 10.2 to 14.6 micrograms/ml with the 600-mg dose and from 29 to 40 micrograms/ml with the 1,200-mg dose. Although concentrations in the brain measured at 6 h tended to be higher in infected rabbits, this difference was not statistically significant. Aztreonam therapy produced a substantial decline in CSF bacterium counts over 6 h: mean CSF counts decreased 2.4 log10 CFU/ml in the 600-mg dose group and 3.0 log10 CFU/ml in the 1,200-mg dose group. The results of this study suggest that aztreonam may be useful in the therapy of meningitis caused by P. aeruginosa.
In vitro susceptibility of Capnocytophaga species to 29 antimicrobial agents
Authors: Rummens J L , Gordts B , Van Landuyt H W
Published: June 2012

A hemoglobin-supplemented medium composed of Columbia agar base supplemented with 1% hemoglobin and 1% Polyvitex was used to investigate the in vitro activity of 29 antimicrobial agents against Capnocytophaga species. Clindamycin was the most active agent, with all strains being inhibited by 0.06 microgram/ml or less. Amoxicillin-clavulanic acid and imipenem were the most active among the beta-lactam antibiotics (MIC for 90% of strains tested [MIC90], 0.50 microgram/ml); other very active drugs were BMY 28142, cefpirome, cefotaxime, ceftazidime, and ceftriaxone (MIC90, 0.06 to 0.50 micrograms/ml), although at least one strain showed resistance to each of these antibiotics (MIC, greater than or equal to 16 micrograms/ml). Ciprofloxacin was the most active among the quinolones, with all strains being inhibited by 0.50 microgram/ml. The MICs of the other four drugs ranged from 0.12 to 4 micrograms/ml. Ampicillin, penicillin G, ticarcillin, aztreonam, and temocillin were moderately active (MIC90, 1 to 8 micrograms/ml; MIC range, less than or equal to 0.03 to greater than 128 micrograms/ml). All strains were uniformly resistant to the aminoglycosides, polymyxin B, vancomycin, trimethoprim, and amphotericin B. Three strains produced beta-lactamase. No significant difference was found between the susceptibility of strains isolated from various sources or patients.
Influence of technical factor variations during inoculum preparation on the agar dilution plate-count method for quantitation of Staphylococcus aureus oxacillin persisters
Authors: Woolfrey B F , Lally R T , Ederer M N
Published: June 2012

The possible introduction of error into Staphylococcus aureus oxacillin intrinsic persister measurements by the agar dilution plate-count method resulting from technical factor variations associated with inoculum preparation was investigated. pH stability and exponential growth were shown to be present at the time of inoculum standardization. The use of glass or plastic tubes and the contamination of tube walls during inoculum broth culture produced no differences in test results. For S. aureus and oxacillin, the agar dilution plate-count method is a new and reliable approach to the quantitative study of bacterial inhibition and killing.
Influence of subinhibitory concentrations of clindamycin on opsonophagocytosis of Staphylococcus aureus, a protein-A-dependent process
Authors: Veringa E M , Verhoef J
Published: June 2012

Incubation in subinhibitory concentrations of clindamycin enhanced the uptake of protein A-rich Staphylococcus aureus strains by polymorphonuclear leukocytes. This enhancement of uptake appeared to be due, in part, to a reduction in the amount of protein A at the bacterial cell surface by clindamycin.
Distribution of porin and lipopolysaccharide antigens on a Pseudomonas aeruginosa permeability mutant
Authors: Godfrey A J , Shahrabadi M S , Bryan L E
Published: June 2012

Pseudomonas aeruginosa common surface antigens were compared in a permeability mutant (PCC118) and its parent (PAO503). The distribution of lipopolysaccharide and porin antigens in the mutant supports the conclusion that beta-lactam permeability was affected by lipopolysaccharide-side chain presentation rather than by a change in porin number.
Antileishmanial activity of liposome-encapsulated amphotericin B in hamsters and monkeys
Authors: Berman J D , Hanson W L , Chapman W L , Alving C R , Lopez-Berestein G
Published: June 2012

Visceral leishmaniasis (kala-azar) results from parasitization of the macrophages of the liver, spleen, and the rest of the visceral reticuloendothelial system with Leishmania donovani. Pentavalent antimony is the drug of choice for leishmaniasis chemotherapy; amphotericin B (AmB) is active but is rarely used, because of drug toxicity. AmB encapsulated within macrophage-directed carriers (liposomes) has been used to treat humans with systemic mycoses complicating neoplastic diseases; dosages of up to 5 mg of encapsulated AmB per kg per day for greater than 14 days are without apparent kidney or liver toxicity. In the present work, greater than 99% of L. donovani parasites were eliminated from the liver and spleen of infected hamsters by one administration of 1.5 to 11 mg of liposome-encapsulated AmB (L-Amb) per kg. A total of 98 to 99% of hepatosplenic parasites were eliminated from squirrel monkeys by three administrations of 4 mg of L-AmB per kg. L-AmB was 170 to 750 times as active as antimony in hamsters, and approximately 60 times as active as antimony in monkeys. The demonstration that apparently nontoxic human dosages of L-AmB eliminate essentially all hepatosplenic parasites in hamster and primate models suggests that this preparation should be considered for clinical trial against kala-azar.
In vitro and in vivo evaluation of A-56268 (TE-031), a new macrolide
Authors: Fernandes P B , Bailer R , Swanson R , Hanson C W , McDonald E , Ramer N , Hardy D , Shipkowitz N , Bower R R , Gade E
Published: June 2012

The in vitro and in vivo antibacterial activity of A-56268 (TE-031), the 6-O-methyl derivative of erythromycin, was compared with those of erythromycin and other reference drugs. A-56268 had the same spectrum of antibacterial activity as erythromycin. A-56268 was generally 1 log2 dilution more potent or equal to erythromycin against all organisms except haemophilus influenzae and Propionibacterium acnes, for which A-56268 was 1 log2 dilution and 3 log2 dilutions, respectively, less potent. The MBC of A-56268 and erythromycin was not significantly different from the MIC against Streptococcus pyogenes, Streptococcus pneumoniae, Staphylococcus epidermidis, and H. influenzae but was more than 2 log2 dilutions higher than the MICs for some Staphylococcus aureus strains. Human serum at a concentration of 50% did not change the in vitro potency of A-56268 or erythromycin. A-56268 was similar to erythromycin in being more active at pH 8.0 than at the physiologic pH of 7.3. The activity of A-56268 was synergistic with sulfamethoxazole against 4 of 12 strains of H. influenzae. In mouse protection tests, when administered orally A-56268 was more potent than erythromycin against H. influenzae, S. pyogenes, S. pneumoniae, and S. aureus. After subcutaneous administration the potencies of A-56268 and erythromycin were not statistically different from each other. A-56268 was more potent than erythromycin against Legionella infection in guinea pigs. The concentration of A-56268 in the serum and lung was higher than that of erythromycin after intraperitoneal administration. In A-56268 in the serum and lung was higher than that of erythromycin after intraperitoneal administration. In mice, the peak levels in serum of A-56268 and erythromycin were similar after subcutaneous administration and seven times higher for A-56268 after oral administration. The serum half-life of A-56268 was approximately twice that of erythromycin after administration by both routes.
Pharmacokinetics of cefoperazone in the parturient
Authors: Gonik B , Feldman S , Pickering L K , Doughtie C G
Published: June 2012

Limited pharmacokinetic data for cefoperazone are available from the parturient. Because cefoperazone has a dual excretory pattern, primarily via the biliary system and secondarily via the kidney, pregnancy-induced physiologic alterations can influence its deposition and clearance. Twelve term parturients receiving cefoperazone prophylaxis after cesarean section were selected for study. After 2 g of cefoperazone was administered for 1 h intravenously, serial blood samples were assayed by high-pressure liquid chromatography. Plasma protein binding of cefoperazone was studied in vitro. The mean peak cefoperazone concentration +/- standard deviation was 169.9 +/- 60.4 micrograms/ml. The mean half-life was 152 min. Total serum clearance was 80.8 +/- 30.8 ml/min. The steady-state volume of distribution was 14.2 +/- 6.0 liters. All subjects had detectable trough levels at the end of the dosage interval, with a mean value of 6.5 +/- 5.2 micrograms/ml. Protein binding of cefoperazone for parturients was 74.3 +/- 10.9%, compared with 87.7 +/- 3.2% in nonpregnant controls (P less than 0.05). These data suggest that cefoperazone deposition can be greatly influenced by pregnancy. However, unlike several other new antimicrobial agents whose excretions are mainly renal, the cefoperazone half-life and thus trough concentration for the parturient more closely resemble that for the nonpregnant subject.
In vitro studies simultaneously examining effect of oxacillin on uptake of radiolabeled streptomycin and on associated bacterial lethality in Staphylococcus aureus
Authors: Zenilman J M , Miller M H , Mandel L J
Published: June 2012

We studied the effects of various concentrations of oxacillin on streptomycin uptake and killing for several strains of Staphylococcus aureus. When streptomycin was present in concentrations below the MIC, addition of oxacillin at concentrations greater than or equal to the MIC was associated with both significantly increased aminoglycoside uptake and killing. In contrast, when streptomycin was present in concentrations above the MIC, no increase of streptomycin uptake was noted with the addition of oxacillin, and killing was no greater than what would have been expected with a simply additive effect. Similar studies in a strain of S. aureus selected for high-level streptomycin resistance also demonstrated increased streptomycin uptake in the presence of concentrations of oxacillin above the MIC; however, killing was no greater than that seen with oxacillin alone. These studies provide data which are potentially important in designing a rational approach to clinical use of combination antibiotic therapy.
Bactericidal activity and killing rate of serum in volunteers receiving ciprofloxacin alone or in combination with vancomycin
Authors: Van der Auwera P , Klastersky J
Published: June 2012

Ten healthy volunteers received the following regimen on different days: vancomycin, 500 mg intravenously; ciprofloxacin, 200 mg intravenously; vancomycin plus ciprofloxacin. Concentrations in serum measured microbiologically at the end of infusion and 1 and 6 h after the end of infusion were, respectively (mean [standard deviation] in milligrams per liter): 32.3 (5.5), 14.2 (2.6), and 4 (0.9) for vancomycin and 3.12 (0.86), 0.78 (0.18), and 0.19 (0.05) for ciprofloxacin. Vancomycin concentration was not affected by the simultaneous administration of ciprofloxacin. The serum bacteriostatic and bactericidal (SBA) activities were measured 1 and 6 h after the end of infusion against five strains each of Staphylococcus aureus susceptible and resistant to oxacillin, Staphylococcus epidermidis susceptible and resistant to oxacillin, Corynebacterium strain JK, and Listeria monocytogenes and three strains of Mycobacterum fortuitum. Ciprofloxacin alone provided low SBAs against the tested strains even 1 h after administration. Vancomycin provided adequate SBAs against staphylococci and Corynebacterium strain JK 1 h after administration. None of the regimens tested showed adequate bactericidal activity against L. monocytogenes and M. fortuitum. The combination of vancomycin with ciprofloxacin was indifferent. This was confirmed by studying the rate of killing in serum. Vancomycin plus ciprofloxacin appeared to be promising for the empiric treatment of infection in immunocompromised patients.
Pharmacokinetics of cefmenoxime in patients with impaired renal function and in those undergoing hemodialysis
Authors: Konishi K
Published: June 2012

The pharmacokinetics of cefmenoxime were studied after a single intravenous 1.0-g dose to 24 subjects grouped according to their renal functions. Creatinine clearance was above 85, 50 to 85, 10 to 50, and below 10 ml/min per 1.73 m2 in groups 1, 2, 3, and 4, respectively. Cefmenoxime obeyed two-compartment-model kinetics in all four groups. The volume of distribution based on the area under the serum concentration-time curve was renal function independent, the average value being 0.270 +/- 0.075 liters/kg. The elimination-phase half-life (t1/2 beta) was 0.82 +/- 0.30 h in group 1, 1.38 +/- 0.36 h in group 2, 3.32 +/- 1.82 h in group 3, and 7.60 +/- 1.28 h in group 4. Cumulative 24-h urinary excretion accounted for 65.5 +/- 7.6% of the dose in group 1 and for 7.50 +/- 3.72% in group 4. Recommendations for dosage adjustment in patients with renal insufficiency are proposed based on the data obtained in this study. The effect of hemodialysis on cefmenoxime pharmacokinetics was studied in six patients in group 4; hemodialysis shortened the average t1/2 beta from 7.60 +/- 1.28 to 4.19 +/- 1.66 h. It was estimated that in a hypothetical anephric subject with a body weight of 60 kg, 5-h hemodialysis would remove 28.2% of the drug present in the body at the start of hemodialysis.
Involvement of outer membrane of Pseudomonas cepacia in aminoglycoside and polymyxin resistance
Authors: Moore R A , Hancock R E
Published: June 2012

Pseudomonas cepacia was found to be resistant to the outer membrane-permeabilizing effects of aminoglycoside antibiotics, polymyxin B, and EDTA. Permeabilization of P. cepacia to the fluorescent probe 1-N-phenylnaphthylamine was not achieved at concentrations 100- to 1,000-fold above those required to permeabilize Pseudomonas aeruginosa. Furthermore, in contrast to P. aeruginosa cells, intact cells of P. cepacia did not bind the fluorescent probe dansyl-polymyxin. However, purified lipopolysaccharide (LPS) from P. cepacia bound dansyl-polymyxin with approximately the same affinity as did LPS from P. aeruginosa. Also, binding of dansyl-polymyxin to P. cepacia (and P. aeruginosa) LPS was inhibited by polymyxin B, streptomycin, gentamicin, and Mg2+. These data suggest that P. cepacia does not utilize the self-promoted pathway for aminoglycoside uptake and that the outer membrane is arranged in a way that conceals or protects cation-binding sites on LPS which are capable of binding polycations such as aminoglycosides or polymxyin.
Characterization of beta-lactamases in situ on polyacrylamide gels
Authors: Sanders C C , Sanders W E , Moland E S
Published: June 2012

An inhibitor-based characterization system which allowed the identification of beta-lactamases after isoelectric focusing on polyacrylamide gels was developed. This system, using potassium clavulanate and oxacillin, distinguished type I chromosomally mediated enzymes from other beta-lactamases of gram-negative bacteria.