Antibiotics

Eur J Pediatr Surg, 1995 Oct, 5(5), 282 - 5
Prophylactic antibiotics in uncomplicated appendicitis during childhood--a prospective randomised study; Soderquist-Elinder C et al.; 544 children operated upon for uncomplicated appendicitis were randomised into three groups . Group I received no antibiotics, patients in Group II were administered one single pre-operative dose of metronidazole (10 mg/kg) and patients in Group III received both both metronidazole (20 mg/kg) and cefuroxime (50 mg/kg) in a single preoperative dose . The rate of infectious complications in Group I was 6.3% but only 2.1 and 2.3 in Groups II and III, respectively . Among patients with a normal appendix or patients with simple appendicitis there was no difference in the rate of post-operative infections between the three different groups . However, in patients with gangrenous appendicitis the rate of postoperative infections was significantly lower in the two groups who received preoperative antibiotics (1.8% and 3.0% respectively) than in the group receiving no prophylactic antibiotics (infection rate 14%) . It is concluded that a single preoperative dose of metronidazole significantly decreases the rate of postoperative infectious complications in children with appendicitis . No further improvement could be demonstrated if cefuroxime against aerobic organisms was added.

J Hand Surg {Br}, 1995 Oct, 20(5), 685 - 90
Post-operative infection following hand surgery . Guidelines for antibiotic use; Platt AJ et al.; An audit was designed to analyse the risk factors for developing post-operative wound infection following hand surgery . 249 consecutive patients were prospectively entered into the study . 236 (95%) patients were available for follow-up . Infection was diagnosed by clinical criteria . There was an infection rate of 10.7% in elective operations and 9.7% in emergency operations . There was no significant reduction in infection rate in the elective group with the use of antibiotics (P = 0.5) . In the emergency group of patients peri-operative antibiotic administration was associated with an 8.5-fold reduction in infection rate (P = 0.014) . The presence of a dirty wound was associated with a 13.4-fold increase in post-operative wound infection rate (P = 0.002) . A postal questionnaire of members of the British Society for Surgery of the Hand revealed a wide variation in antibiotic usage . Guidelines for antibiotic use in patients undergoing hand surgery are presented.

Biosci Biotechnol Biochem, 1995 Oct, 59(10), 1835 - 41
A self-defense gene homologous to tetracycline effluxing gene essential for antibiotic production in Streptomyces aureofaciens; Dairi T et al.; By Northern blot analyses with DNA probes carrying 6-demethylchlortetracycline (6-DCT) biosynthetic genes from Streptomyces aureofaciens NRRL3203, a highly expressed gene (tcrC) was detected in a high titer producing mutant derived from the parental strain NRRL3203 by NTG mutagenesis . The analysis of the nucleotide sequence of the 2.8-kb BamHI fragment containing tcrC gene showed that the predicted tcrC gene product is a protein consisting of 512 amino acids . The deduced amino acid sequence had a high level identity with that of the self-defense gene (tet347) of Streptomyces rimosus, known to mediate oxytetracycline efflux . The tcrC gene-inactivated strains generated from strain NRRL3203 by gene replacement had a 90% decrease in the level of resistance to tetracycline and the antibiotic productivity when compared with the parental strain.

Am J Respir Cell Mol Biol, 1995 Oct, 13(4), 449 - 54
Inhibition of acetylcholine-evoked Cl- currents by 14-membered macrolide antibiotics in isolated acinar cells of the guinea pig nasal gland; Ikeda K et al.; Recent clinical and experimental studies demonstrated that 14-membered macrolides suppressed fluid secretion from respiratory tract mucosa . The cellular mechanisms of acetylcholine (ACh)-induced electrolyte secretion in the acinar cell isolated from the guinea pig nasal gland were investigated by using a microfluorimetric imaging method and a patch-clamp whole-cell recording . The ACh-induced increase in intracellular Ca2+ concentration measured by the fura-2 method was little affected by three types of macrolides, josamycin (JM), erythromycin (EM), and roxythromycin (RXM) . The ACh-evoked ionic currents were not inhibited by a 16-membered macrolide, JM, whereas both 14-membered macrolides, EM and RXM, significantly inhibited membrane conductance, especially inward currents, in a concentration-dependent manner . The ACh-induced Cl- current isolated by the ionic substitutional experiments was remarkably inhibited by EM and RXM . The order of inhibition was RXM > EM >> JM . Thus, 14-membered macrolides showed a direct inhibition of the Cl- conductance activated by ACh.

J Antibiot (Tokyo), 1995 Oct, 48(10), 1153 - 8
New anthracycline antibiotics 10-epi-oxaunomycin and 10-epi-11-deoxyoxaunomycin; Johdo O et al.; Two new anthracycline antibiotics, 10-epi-oxaunomycin and 10-epi-11-deoxyoxaunomycin, were photochemically obtained from anthracycline metabolites D788-1 (10-carboxy-13-deoxocarminomy-cin) and D788-3 (10-carboxy-11-deoxy-13-deoxocarminomycin) and were examined for their growth inhibitory activities on cultured L1210 leukemic cells . Effects of the S configuration of C-10 and a hydroxyl group at C-11 on the bioactivity are discussed in comparison with oxaunomycin and 11-deoxyoxaunomycin.

J Antibiot (Tokyo), 1995 Oct, 48(10), 1134 - 7
Total synthesis of (+/-)-phosphonothrixin, a novel herbicidal antibiotic containing C-P bond; Nakamura K et al.; Phosphonothrixin (1) is a novel herbicidal agent produced by Saccharothrix sp . ST-888, with a unique structure possessing a C-P bond and an isoprene unit . The total synthesis of this antibiotic was accomplished from methyl (bromomethyl)acrylate in six steps.

J Antibiot (Tokyo), 1995 Oct, 48(10), 1130 - 3
Phosphonothrixin, a novel herbicidal antibiotic produced by Saccharothrix sp . ST-888 . II . Structure determination; Kimura T et al.; Phosphonothrixin (1) is a novel herbicidal agent produced by Saccharothrix sp . ST-888 . This unique compound possessing a C-P bond and an isoprene unit was determined to be 2-hydroxy-2-hydroxymethyl-3-oxobutyl-phosphonic acid . Unusually rapid proton-deuterium (H-D) exchange of the methyl ketone unit of this antibiotic in D2O solution was observed . Phosphonothrixin can be classified as a new type of natural product herbicide having a C-P bond in the molecule.

Aten Primaria, 1995 Sep 30, 16(5), 281 - 4
{Analysis of prescriptions of antibiotics for acute respiratory infections at a health center}; Formento Tirado JA et al.; OBJECTIVE . To analyse the prescription of antibiotics for acute respiratory infections (ARI) at our Health Centre . DESIGN . An observational crossover study . SETTING . Primary Health care . San Gregorio de Telde Health Centre, Gran Canaria . PATIENTS AND PARTICIPANTS . Systematic random sampling of 368 clinical cases with ARI . 196 women (53.26%) and 172 men (46.73%), with an average age of 33.26 +/- 1.97 . MEASUREMENTS AND MAIN RESULTS . Antibiotics were prescribed for 42.66% of ARI . Family doctors used them less than general ones (38.67% against 63.04%, p < 0.0001), and on the afternoon lists they were used less than in the morning (33.82% against 52.35%, p < 0.001) . In chronically ill patients they were used less than symptomatic treatment (42.16% against 57.83%, p < 0.001) . There were no significant differences found between their use and the appearance of complications (37.5% with Antibiotherapy against 62.5% without it) or successive consultations (45.16% with antibiotics against 54.83% without them) . They were used more in those aged over 60 (48.97%) and in those who attended less (51.56%) . Average cost per patient treated with Antibiotherapy was 2,508.48 +/- 258.80 pesetas against 694.28 +/- 78.67 pesetas for the patient treated symptomatically (p < 0.0005) . CONCLUSIONS . We are using Antibiotherapy inadequately in our field . We propose that quality control studies to detect and correct problems of this type should be undertaken . In our case corrective measures with a later reevaluation should be applied.

J Med Chem, 1995 Sep 29, 38(20), 4106 - 14
Synthesis and antiproliferative and antiviral activity of 2'-deoxy-2'-fluoroarabinofuranosyl analogs of the nucleoside antibiotics toyocamycin and sangivamycin; Krawczyk SH et al.; The glycosylation of 3,4-dicyano-2-{(ethoxymethylene)amino}pyrrole (7) with 2-deoxy-2-fluoro-alpha-D-erythro-pentofuranosyl bromide (2) furnished an anomeric mixture of nucleosides (8a,b) . This mixture was separated, and the individual anomers were treated with methanolic ammonia to effect a concomitant deblocking and ring closure . This furnished both anomers of 2'-deoxy-2'-fluoro-ara-toyocamycin (9a,b) . The cyano moiety of 9b was converted to the carboxamide moiety to furnish 2'-deoxy-2'-fluoro-ara-sangivamycin (10) and to the thiocarboxamide moiety to furnish 2'-deoxy-2'-fluoro-ara-thiosangivamycin (11) . The target compounds 10 and 11 showed similar antiproliferative activity against L1210 cells in vitro, with IC50's of 3 and 5 microM . Antiviral evaluation revealed a somewhat different pattern of activity . All analogs, both alpha and beta anomers, were active against human cytomegalovirus (HCMV), albeit the beta anomers were most active . The beta anomers also were active against herpes simplex virus type 1 (HSV-1) and human immunodeficiency virus (HIV) . Compound 10 was most active in the series, ca . 10-fold more potent than 11; IC50's for 10 ranged from 4 to 25 nM for HCMV, HIV, and varicella zoster virus (VZV) and from 30 to 500 nM for HSV-1 . Even though compound 10 was cytotoxic, which will probably preclude its use as an antiviral drug (IC50's = 0.2-5.5 microM), the difference between cytotoxicity and activity against HCMV, HIV, and VZV was sufficient to indicate specific activity against a viral target.

J Chromatogr A, 1995 Sep 8, 711(1), 201 - 15
Liquid chromatographic determination of D- and L-amino acids by derivatization with o-phthaldialdehyde and N-isobutyryl-L-cysteine . Applications with reference to the analysis of peptidic antibiotics, toxins, drugs and pharmaceutically used amino acids; Bruckner H et al.; In order to evaluate and extend the applicability of an analytical method that enables the quantitative and simultaneous high-performance liquid chromatographic determination of D- and L-amino acids (DL-AAs) by automated precolumn derivatization with o-phthaldialdehyde together with the chiral thiol N-isobutyryl-L-cysteine {J . Chromatogr., 666 (1994) 259} selected natural and synthetic bioactive peptides, as well as pharmaceutically used formulations of AA, were investigated and the amounts of D- and L-AA determined by fluorescence detection . Peptides containing cys(e)ine were oxidized with performic acid prior to hydrolysis with 6 M HCl, and those containing Trp were hydrolyzed with 4 M methanesulfonic acid (24 h at 110 degrees C in both cases) . Peptides analyzed were the peptide antibiotics bacitracin, gramicidins A and S, polymyxin B, metanicin C, the peptide toxin malformin A and the peptide drugs D-Arg-{Hyp3,Thi5,8,D-Phe7}-bradykinin, beta-casomorphin and alpha s1-exorphin . Further, the enantiomeric ratios of pharmaceutically used AA formulations containing racemic DL-Ser, DL-Asp and DL-Met were determined, and the AA drugs L-Asp and L-Trp were tested negatively for the presence of the respective D-enantiomers . In two aqueous formulations of L-AA used for parenteral nutrition, low amounts of D-AA (0.1-0.9% with respect to certain L-AA enantiomers and of totally 128 mg and 149 mg D-AAs per liter infusion solution) were determined.

Antibiot Khimioter, 1995 Sep, 40(9), 38 - 41
{Experimental and clinical study of antibiotics administered intravitreally in endophthalmitis}; Shenderovich VA et al.; The concentrations of gentamicin and cefotaxime (claforan) in the humor of the anterior chamber and vitreous body of the eye were estimated in the study on the pharmacokinetics of the antibiotics in rabbits . The antibiotics were administered intravitreally in single doses . It was shown that the residence time of the antibiotics in the therapeutic concentrations in the eye cavity was 48 hours . Cefotaxime proved to be the most efficient agent in the prevention and treatment of postoperative endophthalmitis.

Eur Respir J, 1995 Sep, 8(9), 1594 - 604
Inhalation of antibiotics in cystic fibrosis; Touw DJ et al.; Aerosol administration of antipseudomonal antibiotics is commonly used in cystic fibrosis . However, its contribution to the improvement of lung function, infection and quality of life is not well-established . All articles published from 1965 until the present time concerning the inhalation of antibiotics in cystic fibrosis were collected by computerized literature search and analysed . Effective aerosol delivery is compromised by nebulizers with limited capacity to produce particles in the respirable range . Twelve studies concerning maintenance treatment were published . Four uncontrolled studies evaluating antibiotic aerosol maintenance treatment in stable patients indicated a beneficial effect in terms of reducing the number of hospital admissions . Eight placebo-controlled studies were found; six of these showed a significant improvement of lung function in the treatment group . Four studies showed a reduction of the number of hospital admissions . In some studies, there was a considerable negative effect of the nebulized placebo solution on the outcome, probably due to the improper choice of its osmolarity . Studies with antibiotic aerosols as adjunct to intravenous therapy in cystic fibrosis patients with an acute exacerbation showed no enhancement of the clinical effects of the intravenous antibiotic by the aerosol; sputum colony counts, however, were lower . Toxicity studies carried out so far have shown no renal or ototoxicity; however, long-term toxicity studies still have to be performed using higher dosages . Introduction or selection of resistant bacteria is relatively rare, but remains a matter of concern . Aerosol maintenance treatment with an appropriate antibiotic in high enough dosage can be recommended for patients with cystic fibrosis chronically infected with P . aeruginosa, and may improve lung function and reduce the number of hospital admissions due to an acute exacerbation.

West Indian Med J, 1995 Sep, 44(3), 81 - 4
Pharmacoeconomics of intravenous antibiotic use in serious infection; Levett PN et al.; A pharmacoeconomic study of 15 antibiotics available in Barbados was performed . The antibiotics studied were amoxycillin/clavulanate, ampicillin, ampicillin/sulbactam, cefazolin, cefotaxime, ceftazidime, ceftriaxone, clindamycin, cloxacillin, cotrimoxazole, gentamicin, imipenem, metronidazole, piperacillin, piperacillin/tazobactam, and vancomycin . The costs of use of these compounds were calculated for a five-day course using a formula comprising eight categories: antibiotic purchase cost, maintenance of intravenous access, drug delivery cost, drug monitoring cost, dose readjustment, general monitoring cost, 'sharps' disposal cost and adverse effects . The costs of adverse effects were not included in this study due to lack of accurate data . The total cost of antibiotic use (in U.S . dollars) ranged from $42.52 to $463.73 per five-day course . Generic compounds were less expensive ($45.52 - $98.23) than brand-name compounds ($106.18 - $106.18 - $463.73) . Antibiotic purchase costs accounted for proportions of total costs ranging from 7 to 93% . Non-drug costs represented a much greater proportion of total costs of generic compounds . For most compounds the non-drug costs were related to the frequency of dosing, but for gentamicin the non-drug costs were relatively higher because of the need for monitoring of serum gentamicin levels . Efficacy and freedom from side-effects will remain the most important determinants in the choice of antibiotic therapy . However, pharmacoeconomic analyses can provide prescribers with the information required to make cost-effective choices for treatment of their patients.

J Antibiot (Tokyo), 1995 Sep, 48(9), 954 - 61
Anguinomycins C and D, new antitumor antibiotics with selective cytotoxicity against transformed cells; Hayakawa Y et al.; The retinoblastoma protein (pRB) is inactivated during the development of a wide variety of human cancers . In the course of our screening for antitumor antibiotics by using pRB-inactivated cells, an actinomycete strain was found to produce two active substances, which were elucidated to be new members of the leptomycin-anguinomycin family by NMR spectral analysis and were designated anguinomycins C and D . The anguinomycins induced growth arrest against normal cells and induced cell death against transformed cells, in which pRB was inactivated by viral oncoproteins such as human papillomavirus E7, adenovirus E1A and simian virus 40 large T antigen.

J Antibiot (Tokyo), 1995 Sep, 48(9), 1011 - 4
Biosynthetic study on the polyether carboxylic antibiotic, nigericin production and biohydroxylation of grisorixin by nigericin-producing Streptomyces hygroscopicus NRRL B-1865; Mouslim J et al.; With addition of methyl oleate, the increased yield of antibiotic production by nigericin-producing Streptomyces hygroscopicus NRRL B-1865 also resulted in the isolation of three additional polyether antibiotics . Two of these are abierixin and epinigericin, as new antibiotics . The third antibiotic is grisorixin . The production of both abierixin (opened ring A and 30-CH2OH) and grisorixin (ring A and 30-CH3) poses the problem of the identity of the last pathway precursor of the major metabolite, nigericin (ring A and 30-CH2OH) . Transformation experiments of abierixin by S . hygroscopicus gave negative results . Hydroxylation of grisorixin to nigericin by S . hygroscopicus represents the final step in nigericin biosynthesis.

Anticancer Drug Des, 1995 Sep, 10(6), 441 - 50
Prodrugs of anthracycline antibiotics suited for tumor-specific activation; Azoulay M et al.; The two novel prodrugs 4 and 11 have been prepared from tetra-O-acetyl-D-galactopyranose and doxorubicin in three and six steps, respectively . Their low cytotoxicity, high stability in plasma and, in the case of 11, efficient hydrolysis in the presence of alpha-galactosidase, fulfill preliminary conditions for their use in combination with monoclonal antibody-enzyme conjugates.

Orthop Nurs, 1995 Sep-Oct, 14(5), 69 - 70
Local application of antibiotics in orthopaedic infections; Gray MA; Local administration of high doses of antibiotics may be done with the use of antibiotic beads . The advantages of this treatment modality would seem to outweigh the disadvantages.

J Thorac Cardiovasc Surg, 1995 Sep, 110(3), 680 - 7
Allograft heart valve sterilization: a six-year in-depth analysis of a twenty-five-year experience with low-dose antibiotics; Gall K et al.; At the Prince Charles Hospital, from a 25-year experience with allograft heart valves (1969 to 1994), a 6-year analysis from March 1988 to August 1994 of the contamination rates and efficiency of a short-duration, low-dose antibiotic sterilization protocol was made . This analysis covered 642 collections and 680 aortic and pulmonary valve implants . Tissue samples obtained at collection, valve trimming, postantibiotic incubation, and implant provided the raw data . At collection, valves retrieved in open mortuaries produced the highest contamination rate of 54% . Minimal exposure to antibiotics during transport and trimming reduced the contamination rate to 11% (p < 0.05) . This was similar to the contamination rate at trimming for valves collected in the "sterile" operating room from multiorgan donors (12%) . Antibiotic incubation at 37 degrees C for 6 hours reduced the contamination rate to 4% (p < 0.05) . Only valves that showed no contamination at cryopreservation were implanted . However, at implant, resected tissue from valves that had been incubated in antibiotics showed a contamination rate of 3%, presumably from the theater environment, compared with 15% (p < 0.05) for tissue from valves that had not been incubated . A residual antibiotic effect appears present at the time of implant in valves that have been incubated in antibiotics and may assist in the reduction of and resistance to infection in the immediate postoperative period . This is supported by the low incidence of endocarditis in the first 3 postoperative months . The simple and effective protocol of collection within 24 hours of death combined with low-dose antibiotic sterilization is sufficient to produce pathogen-free valves in the majority of cases (> 95%).

Neurosurgery, 1995 Sep, 37(3), 418 - 21
Antibiotic penetration into cervical discs; Rhoten RL et al.; Antibiotics are frequently prophylactically administered in surgical procedures to reduce the incidence of infection . The penetration of antibiotics into lumbar discs has been studied with mixed results, but penetration into cervical discs has not been reviewed . In this study, we examined the penetration of two commonly used antibiotics, oxacillin and cefazolin, into cervical discs . Eighteen patients with a total of 30 discs removed were studied . Two groups, each consisting of four patients with five discs removed, received either 1 g of oxacillin or 1 g of cefazolin by a single, preoperative intravenous infusion . Two other groups, each consisting of five patients with 10 discs removed, received either 2 g of oxacillin or 2 g of cefazolin, also by a single, preoperative intravenous infusion . A blood specimen, from which serum antibiotic levels were determined, was obtained from each patient simultaneously with each discectomy . The time interval between the antibiotic infusion and discectomy/phlebotomy was also recorded . Antibiotic levels were detected in all discs removed but were quantifiable in only 12 . Nine of these 12 had been exposed to cefazolin . Of these nine discs, one was from a patient who had received 1 g whereas the other eight were from patients who had received 2 g of cefazolin . This represents 80% of the removed discs exposed to 2 g of cefazolin (10 discs total) and 20% exposed to 1 g (5 discs total) . The remaining three discs with quantifiable antibiotic levels had been exposed to 2 g of oxacillin, which represents 30% of the discs (10 total) exposed to that dose of oxacillin . Although cervical disc space infections are rare, they are serious.(ABSTRACT TRUNCATED AT 250 WORDS)

Infect Dis Clin North Am, 1995 Sep, 9(3), 575 - 90
Antibiotic concerns in the elderly . A clinician's perspective; Gleckman RA; Unique antibiotic concerns exist for the management of infections in elderly patients . Issues concerning age-associated physiological alterations, compliance, drug-drug interactions, adverse drug reactions, and guidelines for empiric therapy are reviewed in this article.

FEMS Microbiol Lett, 1995 Aug 15, 131(1), 27 - 34
Giant linear plasmids of beta-lactam antibiotic producing Streptomyces; Netolitzky DJ et al.; A survey of the total cellular DNA from five beta-lactam antibiotic-producing Streptomyces spp . by pulsed field gel electrophoresis was conducted to investigate the presence of linear plasmids . Streptomyces clavuligerus NRRL 3585 contained two giant linear plasmids of 120 and 430 kb, in addition to the well-characterized 11.7 kb linear plasmid . Streptomyces griseus NRRL 3851 contained a single giant linear plasmid of 120 kb, and Streptomyces jumonjinensis NRRL 5741 contained two giant linear plasmids (220 and 280 kb), and two smaller linear plasmids . No plasmids were identified in Streptomyces cattleya NRRL 3841 or Streptomyces lipmannii NRRL 3584 . Southern hybridization did not reveal any homology shared by these plasmids, and beta-lactam antibiotic synthesis gene clusters were located on the chromosome.

J Pharm Technol, 1995 Sep-Oct, 11(5), 203 - 10
Use of benchmarking techniques to justify the evolution of antibiotic management programs in healthcare systems; Schentag JJ et al.; OBJECTIVE: To apply basic benchmarking techniques to hospital antibiotic expenditures and clinical pharmacy personnel and their duties, to identify cost savings strategies for clinical pharmacy services . DESIGN: Prospective survey of 18 hospitals ranging in size from 201 to 942 beds . Each was asked to provide antibiotic expenditures, an overview of their clinical pharmacy services, and to describe the duties of clinical pharmacists involved in antibiotic management activities . Specific information was sought on the use of pharmacokinetic dosing services, antibiotic streamlining, and oral switch in each of the hospitals . RESULTS: Most smaller hospitals (< 300 beds) did not employ clinical pharmacists with the specific duties of antibiotic management or streamlining . At these institutions, antibiotic management services consisted of formulary enforcement and aminoglycoside and/or vancomycin dosing services . The larger hospitals we surveyed employed clinical pharmacists designated as antibiotic management specialists, but their usual activities were aminoglycoside and/or vancomycin dosing services and formulary enforcement . In virtually all hospitals, the yearly expenses for antibiotics exceeded those of Millard Fillmore Hospitals by $2,000-3,000 per occupied bed . In a 500-bed hospital, this difference in expenditures would exceed $1.5 million yearly . Millard Fillmore Health System has similar types of patients, but employs clinical pharmacists to perform streamlining and/or switch functions at days 2-4, when cultures come back from the laboratory . CONCLUSIONS: The antibiotic streamlining and oral switch duties of clinical pharmacy specialists are associated with the majority of cost savings in hospital antibiotic management programs . The savings are considerable to the extent that most hospitals with 200-300 beds could readily cost-justify a full-time clinical pharmacist to perform these activities on a daily basis . Expenses of the program would be offset entirely by the reduction in the actual pharmacy expenditures on antibiotics.

J Biol Chem, 1995 Aug 4, 270(31), 18234 - 9
Biosynthesis of the macrolide oleandomycin by Streptomyces antibioticus . Purification and kinetic characterization of an oleandomycin glucosyltransferase; Quiros LM et al.; The oleandomycin (OM) producer, Streptomyces antibioticus, possesses a mechanism involving two enzymes for the intracellular inactivation and extracellular reactivation of the antibiotic . Inactivation takes place by transfer of a glucose molecule from a donor (UDP-glucose) to OM, a process catalyzed by an intracellular glucosyltransferase . Glucosyltransferase activity is detectable in cell-free extracts concurrent with biosynthesis of OM . The enzyme has been purified 1,097-fold as a monomer, with a molecular mass of 57.1 kDa by a four-step procedure using three chromatographic columns . The reaction operates via a compulsory-order mechanism . This has been shown by steady-state kinetic studies using either OM or an alternative substrate (rosaramycin) and dead-end inhibitors, and isotopic exchange reactions at equilibrium . OM binds first to the enzyme, followed by UDP-glucose . A ternary complex is thus formed prior to transfer of glucose . UDP is then released, followed by the glycosylated oleandomycin (GS-OM).

Antibiot Khimioter, 1995 Aug, 40(8), 7 - 11
{Reaction of acylation of the antineoplastic antibiotic bleomycetin}; Usol'tseva SV et al.; The reaction of benzoylation of bleomycetin, a glycopeptide antibiotic, and its cuprum complex was studied with the chloranhydride and carbodiimide methods . Acylation of the antibiotic cuprum complex by an equivalent quantity of benzoyl chloride resulted in formation of a mixture of mono- and disubstituted derivatives while with the use of a 3-fold excess of chloranhydride it was possible to obtain dibenzoylbleomycetin as a sole reaction product . Interaction of the bleomycetin cuprum complex with activated benzoic ether resulted in formation of a product monosubstituted by the antibiotic spermidine fragment . After acylation of the free antibiotic by the carbodiimide and chloranhydride methods tri- and tetrabenzoyl derivatives of bleomycetin were isolated respectively.

J Indian Med Assoc, 1995 Aug, 93(8), 293 - 4, 290
Role of antibiotics in clean wounds; Hedawoo JB et al.; Two hundred twenty cases with clean surgical wounds were treated without administering any antibiotics . Majority of them (134) were hydroceles and hernias . The study included some major operation also . The infection rate was 3.6% in the present series, which is comparable with the study where antibiotics were used.

Rheum Dis Clin North Am, 1995 Aug, 21(3), 817 - 34
Antibiotic therapy for rheumatoid arthritis . Scientific and anecdotal appraisals; Trentham DE et al.; Minocycline is arguably the most interesting new drug for rheumatoid arthritis since the development of methotrexate . Tetracycline compounds have long been used by rheumatologists who were considered mavericks by their peers, and recent controlled studies have demonstrated their antirheumatic activity . The reason that minocycline works is unclear, and their niche in the treatment of rheumatoid arthritis remains to be established . Nonetheless, it is clear that some patients with rheumatoid arthritis respond favorably to this form of treatment.

Voen Med Zh, 1995 Aug, (8), 31 - 3, 80
{The efficacy of treating skin ulcers and burns with film dressings with antibiotics}; Morozov VM et al.; The article summarizes the results of studies conducted during the treatment of burns (108 patients), and ecthymas (85 patients) with the help of film dressing and antibiotic powder (R . Breitman's method) . During application of this method the healing process was more rapid, the administration of antibiotics was minimum, the dressing process became more easy, good cosmetic results were obtained . The period of inpatient care was shortened, cost of treatment was reduced.

J Arthroplasty, 1995 Aug, 10(4), 470 - 5
Use of antibiotic-impregnated cement during hip and knee arthroplasty in the United States; Heck D et al.; A survey of practicing orthopaedists regarding their use of antibiotic(s) in bone-cement (ABC) was carried out . The initial sampling of 2,139 orthopaedists spanned the continental United States . Responses that passed fail-edit criteria were obtained from 1,015 physicians . Clinical practice patterns are highly variable . Adult reconstructive orthopaedic practitioners' belief in antibiotic(s) in bone-cement for the treatment of patients with previous sepsis is favorable . This opinion can be supported at the guideline level . Guidelines suggesting that liquid antibiotics should not be used as additions to polymethyl methacrylate are also supportable . The need for careful scientific inquiry and cost-effectiveness evaluation of the benefits and risks relating to the use of antibiotic additions to polymethyl methacrylate cement in joint arthroplasty exists . On the basis of such inquiry, educational dissemination to reduce practice variation would be indicated.

J Arthroplasty, 1995 Aug, 10(4), 453 - 9
Effect of varying surface patterns on antibiotic elution from antibiotic-loaded bone cement; Masri BA et al.; In an effort to improve the antibiotic elution characteristics of the prosthesis of antibiotic-loaded acrylic cement, an in vitro study was conducted . Tobramycin-loaded bone cement blocks of three different surface patterns with different surface area-to-volume ratios were used . The elution of tobramycin over a 2-month period was investigated . There was a gradual decline in the tobramycin elution rate over time . The surface pattern with the increased surface area-to-volume ratio showed a significant increase in the tobramycin elution rate over the first week of the study . The surface pattern with ridges but no change in the surface area-to-volume ratio did not result in a statistically significant increase in the tobramycin elution rate.

Cancer Lett, 1995 Aug 1, 94(2), 171 - 7
Effects of an antibiotic protease inhibitor, actinonin on the growth within collagen gels of non-metastatic and metastatic mouse mammary tumors of the same origin; Sayama K et al.; Of five autonomous sublines established independently from the transplantable hormone-dependent mouse mammary tumor, TPDMT-4, three but not two acquired metastatic potential . In in vitro culture using collagen gels, actinonin, an antibiotic protease inhibitor exerted a stronger growth-inhibiting effect on the metastatic than on the parent and non-metastatic tumors . Zymographic analysis demonstrated the active forms of gelatinases in the metastatic but not in the non-metastatic sublines and the complete inhibition of the enzyme activities by actinonin . Gelatinases/type IV collagenases might play an important role in tumor progression towards metastatic phenotype and actinonin may suppress tumor growth through inhibiting collagenase.

J Antibiot (Tokyo), 1995 Aug, 48(8), 850 - 62
Structural elucidation of aculeximycin . IV . Absolute structure of aculeximycin, belonging to a new class of macrolide antibiotics; Murata H et al.; Aculeximycin (1) produced by Streptosporangium albidum possesses a 30-membered polyhydroxy macrocyclic lactone and five sugars including aculexitriose . We have described the determination of the planar structure of N-diacetylated aculeximycin (2) using degradation products, which were obtained by DBU-methanol treatment, ozonolysis and periodative oxidation . In order to determine the relative and absolute configurations of aculeximycin, first, the relative and absolute configurations of the degradation products 10, 11, 12 and 13 were determined . Rychnovsky's method was very useful to determine the relative configurations of these degradation products, and CD exciton chirality and the modified Mosher's methods were applied to determine their absolute configurations . From these results, fourteen out of the twenty asymmetric centers in aculeximycin were determined to be 5S, 17R, 20S, 21R, 23R, 24R, 29S, 30R, 31S, 34R, 35S, 36S and 37R . The absolute configurations at C-14 and C-15 on the hemiketal ring were confirmed using 12 obtained by the partial glycol bond cleavage of 9 . Absolute configurations of the remaining asymmetric centers were determined by spectral analysis of 15 and NOE experiment on 1 . From these results, the absolute configuration of 1 was determined to be 5S, 7R, 10S, 11R, 14R, 15S, 17R, 19R, 20S, 21R, 23R, 24R, 25S, 29S, 30R, 31S, 34R, 35S, 36S and 37R.

J Antibiot (Tokyo), 1995 Aug, 48(8), 838 - 49
Structural elucidation of aculeximycin . III . Planar structure of aculeximycin, belonging to a new class of macrolide antibiotics; Murata H et al.; The planar structure of aculeximycin (1) produced by Streptosporangium albidum has been determined by spectral methods and chemical degradations such as 1,8-diazabicyclo{5,4,0}undec-7-ene (DBU)-methanol reaction, ozonolysis, and periodative oxidation . The antibiotic consists of a 30-membered polyhydroxy lactone ring, an alpha, beta-unsaturated ester group, an intramolecular hemiketal, an oligosaccharide (aculexitriose), a neutral sugar and an amino sugar . The structure of aculeximycin is closely related to those of sporaviridins produced by Streptosporangium viridogriseum . We consider that aculeximycin and sporaviridins belong to a new class of macrolide antibiotics, which is different from the polyol macrolides produced by Streptomyces.

J Antibiot (Tokyo), 1995 Aug, 48(8), 824 - 30
Induction of differentiation of HL-60 cells by the anti-fungal antibiotic, radicicol; Shimada Y et al.; The anti-fungal antibiotic, radicicol, produced in the culture broth of Neocosmospora tenuicristata, was found to induce differentiation of HL-60 cells into macrophages from the following evidence: (1) it caused morphological changes into macrophage-like cells, (2) induced NBT (Nitrobluetetrazolium) reduction activity, (3) induced phagocytosis, and (4) induced alpha-naphthyl acetate esterase activity . The concentration of radicicol required to differentiate HL-60 cells is 50-100 ng/ml, and the incubation time required for commitment of differentiation is 16 hours . Flow cytometry analysis indicated that radicicol blocks the cell cycle of HL-60 cells at the G1 and G2 sites . In addition, radicicol induced reversal of the transformed phenotype of ras-transformed NIH3T3 cells (DT cells) at 25 ng/ml.

J Antibiot (Tokyo), 1995 Aug, 48(8), 811 - 4
Resistance to the polyether ionophore antibiotic pandavir (nigericin) in two producing strains of Streptomyces; Moncheva PA et al.; In two pandavir (nigericin) producing strains, Streptomyces hygroscopicus 155 and Streptomyces albogriseolus 444, an enzyme activity was detected leading to inactivation of the antibiotic in the presence of ATP-Na2 . Apparently, the observed inactivation is specific for the antibiotic produced by these strains . The nigericin producing strains were also found to be less permeable to pandavir than their non-producing variants.

J Clin Anesth, 1995 Aug, 7(5), 425 - 39
Antibiotic therapy and the anesthesiologist; Cheng EY et al.; The anesthesiologist is frequently responsible for administering antibiotics in the immediate preoperative and intraoperative periods . Anesthesiologists often are not trained in the administration of antibiotics, which can be associated with both acute and long-term complications including potentiation of neuromuscular blocking agents, allergic reactions, and end-organ toxicity . The indications for perioperative antibiotics, proper method of administration, and occurrence and treatment of major side effects of the more commonly recommended prophylactic antibiotics are discussed.

J R Soc Health, 1995 Aug, 115(4), 231 - 4
Compliance with short-term antibiotic therapy among patients attending primary health centres in Riyadh, Saudi Arabia; al-Shammari SA et al.; Non-compliance results in several undesired consequences . Admissions due to non-compliance have been estimated to account for up to 10.5% of all admissions to hospital . There seems to be very little data about compliance in Saudi Arabia . The present study addressed the problem of non-compliance with short-term antibiotic therapy in patients attending Primary Health Centres (PHC) . The data were collected from five different centres selected randomly from the 53 centres in the Riyadh area, Saudi Arabia . A five-part questionnaire was designed and used to collect data . Different parts were required to be completed by patient, doctor, pharmacist and social worker . At the end of the study period 414 questionnaires were suitable for evaluation . Paediatric patients (< 15 years old) constituted 65.9% of the sample . Compliance was noted in 67.8% . Those who missed three doses or less and more than three doses were 22.7% and 9.4% respectively . Factors which appeared to enhance patient compliance were: parental involvement (p < 0.001), unemployment (p < 0.01), absence of psychiatric illness (p < 0.02) and early improvement of symptoms (p < 0.05) . Reasons most frequently mentioned by patients for non-compliance were: rapid improvement of symptoms, bitter taste of drug(s), forgetfulness and frequent dosing . These reasons accounted for 73.7% of reasons for non-compliance . Our findings suggest that approximately two thirds of patients were compliant with their medications . It is also worth noting that approximately three quarters of patients were not compliant for reasons which could be minimised or removed by good patient counselling and effective communication with patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Microbiology, 1995 Aug, 141 ( Pt 8), 1793 - 803
A new Myxococcus xanthus gene cluster for the biosynthesis of the antibiotic saframycin Mx1 encoding a peptide synthetase; Pospiech A et al.; The gene cluster for the biosynthesis of the heterocyclic quinone antibiotic saframycin Mx1 of Myxococcus xanthus DM504/15 was inactivated and tagged by Tn5 insertions . The tagged genes were cloned in Escherichia coli and used to select overlapping cosmid clones spanning 58 kb of the M . xanthus genome . Gene disruption experiments defined a > or = 18 kb contiguous DNA region involved in saframycin biosynthesis . Sequencing of part of this region revealed a large ORF containing two 600-amino-acid domains with similarity to peptide synthetase amino-acid-activating sequences, suggesting that saframycin Mx1 is synthesized by a nonribosomal multienzyme complex, similar to other bioactive peptides.

Pancreas, 1995 Aug, 11(2), 132 - 40
Therapeutic regimens in acute experimental pancreatitis in rats: effects of a protease inhibitor, a beta-agonist, and antibiotics; Araida T et al.; The osmolality of contrast injected retrograde into the rat pancreatic duct did not affect the severity of the pancreatitis (Urografin, 1,300 mOsm/kg, and Hexabrix, 580 mOsm/kg) . The severity of the pancreatitis induced in rats was assessed by survival rate, histologic grading, wet lung ratio, and serum levels of amylase, lipase, and trypsin-like activity . Rats with pancreatitis induced by retrograde injected Urografin, lipopolysaccharide, taurocholic acid plus enterokinase were treated with either intravenous (i.v.) FUT-175 (Nafamstat Mesilate), FUT-175 administered by retrograde pancreatic injection, i.v . terbutaline, i.v . piperacillin sodium, piperacillin sodium by retrograde pancreatic duct injection, or a combination of FUT-175 plus terbutaline and piperacillin . Survival among the rats was increased and the incidence of pancreatic infection reduced in rats treated with i.v . piperacillin or with a combination of FUT-175 plus i.v . terbutaline, plus i.v . piperacillin compared to controls.

Biochemistry, 1995 Jul 25, 34(29), 9632 - 44
Conformation of A82846B, a glycopeptide antibiotic, complexed with its cell wall fragment: an asymmetric homodimer determined using NMR spectroscopy; Prowse WG et al.; Proton NMR assignments were determined for the asymmetric dimer complex of A82846B with the pentapeptide cell-wall fragment . A total of 683 experimental constraints, both distance and dihedral, were collected from NOESY and COSY data sets . From these constraints, a total of 80 structures were calculated using standard X-PLOR protocols . These structures were subsequently refined using the full CHARMm potential and the addition of water molecules in the calculation . The CHARMm structures occupied more conformational space than did the X-PLOR structures and were utilized for the structure analysis . From the structures, a unique set of interactions for the dALA-5 carboxylate pocket was observed, having backbone amides from residues 2 and 3 hydrogen bonding one carboxylate oxygen while amide 4 and the side chain amide from Asn-3 hydrogen bond the other oxygen . Also, near the N-terminal region of the ligand, the GGLU-2's carboxylate forms a hydrogen bond with the asymmetric disaccharide dyad, which helps to define the interactions seen for this part of the ligand.

Biochem Biophys Res Commun, 1995 Jul 17, 212(2), 428 - 32
A DNA-binding antitumor antibiotic binds to spectrin; Majee S et al.; Aureolic acid group of antibiotics inhibit transcription by reversible binding to DNA in presence of divalent magnesium . We for the first time report binding of the one of such antitumor antibiotic, mithramycin (MTR), to the major protein component of erythrocyte cytoskeleton, spectrin . A reasonably high apparent dissociation constant was estimated to be 1.5 microM . The binding of mithramycin in the absence of any divalent cation to the large cytoskeletal protein led to quenching in the tryptophan fluorescence of the protein . Stern-Volmer quenching of the tryptophan residues by acrylamide revealed conformational change in the MTR-bound spectrin . This preliminary study might be useful in understanding other possible sites of actions after translocation.

Carbohydr Res, 1995 Jul 10, 271(1), 55 - 63
The complete 1H NMR assignments of aminoglycoside antibiotics and conformational studies of butirosin A through the use of 2D NMR spectroscopy; Cox JR et al.; The complete proton assignments of the aminoglycoside antibiotics, butirosin A, kanamycin A and kanamycin B, at pH 6.5 have been made through the use of various homonuclear and heteronuclear 2D NMR methods . Butirosin A NOESY experiments suggest a stacking arrangement between the xylose and 2,6-diamino-2,6-dideoxyglucose rings, while the 2-deoxystreptamine ring and its substituent, the (S)-4-amino-2-hydroxybutyryl group, extend away from the stacked rings . Informative long-range NOEs were observed for butirosin A but not with kanamycin A or kanamycin B . Many intra-ring NOEs were observed with all three aminoglycosides that confirm the proton assignments made in this study.

Biochim Biophys Acta, 1995 Jul 6, 1237(1), 1 - 5
Formation of membrane channels by chrysospermins, new peptaibol antibiotics; Grigoriev P et al.; The four homologous chrysospermins (Ia-d) are new 19 amino acid peptaibols which form cation selective ion channels in artificial lipid bilayer membranes . Conductance of channels formed by chrysospermins B (Ib) and D (Id) was twice as high (640 pS in 100 mM KCl) as found with chrysospermins A (Ia) and C (Ic) . Single channel current traces were recorded for each of the four peptides even at very low (even zero) membrane voltages suggesting that non-gated channels are formed.

EMBO J, 1995 Jul 3, 14(13), 3247 - 51
Enhancement of Neurospora VS ribozyme cleavage by tuberactinomycin antibiotics; Olive JE et al.; Several examples of inhibition of the function of a ribozyme or RNA-protein complex have shown that certain antibiotics can interact specifically with RNA . There are, however, few examples of antibiotics that have a positive, rather than a negative, effect on the function of an RNA . We have found that micromolar concentrations of viomycin, a basic, cyclic peptide antibiotic of the tuberactinomycin group, enhance the cleavage of a ribozyme derived from Neurospora VS RNA . Viomycin decreases by an order of magnitude the concentration of magnesium required for cleavage . It also stimulates an otherwise insignificant transcleavage reaction by enhancing interactions between RNA molecules . The ability of viomycin to enhance some RNA-mediated reactions but inhibit others, including translation and Group I intron splicing, demonstrates the potential for natural selection by small molecules during evolution in the 'RNA world' and may have broader implications with respect to ribozyme expression and activity in contemporary cells.

Anal Chem, 1995 Jul 1, 67(13), 2088 - 95
Effect of micelles and mixed micelles on efficiency and selectivity of antibiotic-based capillary electrophoretic enantioseparations; Rundlett KL et al.; Vancomycin (an oligophenolic, glycopeptide, macrocyclic antibiotic) has been shown to be a superb chiral selector for anionic and neutral compounds . It was found that adding sodium dodecyl sulfate to the run buffer increased efficiency by over 1 order of magnitude, decreased analysis times, and reversed the elution order of the enantiomers . This allows for control of the retention order as well as the resolution of enantiomers in complex mixtures in a single run . A mechanism is proposed which explains all of the observed effects and is verified experimentally . Since vancomycin is present in both the micelle and in free solution, previously proposed micelle-selector models are, at best, limiting cases . A general equation is derived which can be used to describe all possible interactions, including those with the capillary wall, if needed . Also, it is shown that electrophoretic mobilities and not migration times must be used to calculate binding constants of a solute to the micelle, the chiral selector, or both . Furthermore, it is shown that a neutral marker molecule cannot be used to accurately correct mobilities that have been altered due to changes in solution viscosity . While this work utilizes the practical vancomycin-micelle system, the general conclusions and theory apply to most other analogous CE systems as well.

Antibiot Khimioter, 1995 Jul, 40(7), 25 - 9
{Effect of antibiotics on glucocorticoid receptor function}; Golikov PP; The effects of penicillin G and cefazolin (cefamezin) on the function of the types II and III glucocorticoid receptors of the liver cytosol were studied on Wistar male rats weighing 180-200 g . The Scatchard and Lineweaver--Berk analysis showed that penicillin G and cefazolin (0.1-10.0 mM) induced a dose-dependent increase in the density of the type III glucocorticoid receptors and a decrease in the affinity of 3H-corticosterone with the type III glucocorticoid receptors . The activation of the function of the type III glucocorticoid receptor by penicillin G and cefazolin was not competitive . Penicillin G had no significant effect on the function of the type II glucocorticoid receptors . The increase in the density of the type II glucocorticoid receptors under the effect of cefazolin was dose-dependent though Ka and Kd did not significantly change . The results were indicative of the fact that penicillins and cephalosporins had a strong action on the most important regulatory system of homeostasis, i.e . the glucocorticoid function which is the decisive one in the pathogenesis of inflammation.

Med Clin North Am, 1995 Jul, 79(4), 919 - 33
Antibiotic dosing in renal failure; Maderazo EG; The Dosing in Renopathy by Easy-To-Use Multipliers (DREM) System is a simple method for dose adjustments of anti-infectives in renal insufficiency . The simple 2-step method involves: (1) estimating creatinine clearance (CLcr) from age, sex, and serum creatinine, and (2) calculating the adjusted dose or dosing interval with the use of multipliers . By multiplying the normal dose or dosing interval with the dose (CLcr/100) or interval (100'CLcr) multiplier, the adjusted dose or dosing interval is obtained, respectively . Dose estimates with this method are reasonably accurate and compare favorably with previously published methods of correction.

Cornea, 1995 Jul, 14(4), 382 - 7
An in vitro comparison of the susceptibilities of bacterial isolates from patients with conjunctivitis and blepharitis to newer and established topical antibiotics; Everett SL et al.; This retrospective study compared new and established topical antibiotics with regard to the in vitro susceptibility of bacterial isolates recovered from patients with conjunctivitis (n = 385) and blepharitis (n = 173) using the National Committee for Clinical Laboratory Standards-approved disk diffusion method . The percent susceptibility of recovered isolates to single antibiotic agents or combinations were ranked from greatest to least: chloramphenicol, bacitracin/polymyxin B, ofloxacin, sulfa, ciprofloxacin, trimethoprim/polymyxin B, norfloxacin, gentamicin, bacitracin, trimethoprim, tobramycin, neomycin, erythromycin, and polymyxin B . We determined that none of the available topical antibiotics provided 100% broad spectrum coverage in vitro . Established antibiotics often provided coverage comparable to the newer drugs . Due to the unproven value of in vitro testing as a predictor of clinical outcome in bacterial blepharitis and conjunctivitis, the ophthalmologist should choose therapy based on clinical experience, ongoing critical evaluation of available antibiotics, and cost-effectiveness.

J Ind Microbiol, 1995 Jul, 15(1), 49 - 54
Bioconversion capacity of Streptomyces sp GE44282, a producer of the antibiotics heneicomycin and aurodox; Marinelli F et al.; Streptomyces sp GE44282 was isolated in the course of a screening program for novel antibiotics . It co-produces heneicomycin and aurodox, two kirromycin-type antibiotics, which differ by the presence of an hydroxyl group at the C30 position of aurodox . Heneicomycin is converted into aurodox both by growing and resting cells of Streptomyces sp GE44282 and by the producer of aurodox, Streptomyces goldiniensis ATCC 21386 . This bioconversion of heneicomycin is substrate-specific and is not observed using the producer of heneicomycin, Streptomyces filippiniensis NRRL 11044 . The three strains show very similar taxonomic characteristics . These results suggest that heneicomycin is a precursor of aurodox, the production of which depends on the bioconversion capability expressed by the strain.

Trop Doct, 1995 Jul, 25(3), 115 - 7
Aggressive fluid resuscitation and broad spectrum antibiotics decrease mortality from typhoid ileal perforation; Mock C et al.; One of the most severe complications of typhoid enteritis is perforation of ileal ulcerations . The typically high mortality rates from these perforations are in part due to extremely limited supportive care in hospitals in typhoid endemic areas . In the setting of a rural African hospital, this study demonstrated a decrease in overall mortality rate from 40% with one layer closure and chloramphenicol alone to 19% with two-layer closure and chloramphenicol, gentamicin and metronidazole . This was primarily due to a decrease in late (> 24 h) mortality . There was also a decrease in overall mortality rate from 43% with < 10 ml/kg of intraoperative fluid administration to 14% with > 10 ml/kg . This was primarily due to a decrease in early (< 24 h) mortality . Even within the constraints of the rural developing world, more aggressive initial fluid resuscitation can decrease early mortality, while broader spectrum antibiotics and two-layer closure can decrease late mortality from typhoid ileal perforation.

J Antibiot (Tokyo), 1995 Jul, 48(7), 683 - 95
Synthesis of new pseudodisaccharide aminoglycoside antibiotics from carbohydrates; Pelyvas IF et al.; Novel pseudodisaccharide-type aminocyclitol antibiotic models, built up from D-arabinose, D-ribose, D-glucosamine, L-ristosamine and L-acosamine have been synthesized by the glycosylation of suitably protected (azido)deoxyinosose aglycones derived by the Ferrier carbocyclic ring transformation of carbohydrate precursors . An alternative approach to related pseudodisaccharides, based on the Ferrier carbocyclization of reducing disaccharides, has also been elaborated . This latter method extends the scope of the Ferrier reaction, by demonstrating that acid-labile 2-deoxydisaccharides can also be readily transformed into the corresponding pseudodisaccharides under the slightly acidic conditions of this ring-transformation.

J Antibiot (Tokyo), 1995 Jul, 48(7), 614 - 8
Fusacandins A and B; novel antifungal antibiotics of the papulacandin class from Fusarium sambucinum . II . Isolation and structural elucidation; Hochlowski JE et al.; Two novel antifungal compounds of the papulacandin class, named fusacandins A and B, have been isolated from Fusarium sambucinum . Each compound contains two units of galactose and one of glucose, the latter connected as a C-glycoside to an aromatic moiety . Fusacandin A is esterified at two sites with long-chain, unsaturated fatty acids and fusacandin B at only one site . The structures of the fusacandins were elucidated through analysis of mass spectral and 1-D and 2-D homonuclear and heteronuclear NMR data.

Free Radic Biol Med, 1995 Jul, 19(1), 31 - 7
Hydrogen peroxide as a potent bacteriostatic antibiotic: implications for host defense; Hyslop PA et al.; Host defense against bacterial pathogens in higher organisms is mediated in part by the generation of reactive oxygen species (ROS) by PMN . In this study, we determined the following effects of exposure of constant concentrations of H2O2 on E . coli in a culture continuously monitored for H2O2 concentration, numbers, and viabilities of cells: (1) E . coli growth rates monitored for 1 h were profoundly affected by concentrations of H2O2, between 25-50 microM . (2) Complete bacteriostasis was observed at 100 microM . (3) Significant cell killing was not observed until the concentration of H2O2 was greater than 500 microM . (4) Bacteriostatic (25-50 microM) concentrations of H2O2 appeared not to be toxic to human skin fibroblasts for a 2-h exposure . (4) Bacteriostasis by H2O2 could not be explained by metabolic inhibition, because intracellular ATP levels were not compromised at bacteriostatic doses of H2O2 . (5) Measurements of H2O2 concentrations in subcutaneous abscess fluid infected with both E . coli and S . aureus indicated prevailing concentrations of the oxidant consistent with a proposed role of H2O2 in host defense.

J Pharmacol Exp Ther, 1995 Jul, 274(1), 194 - 9
Effects of nephrotoxic beta-lactam antibiotics on the mitochondrial metabolism of monocarboxylic substrates; Tune BM et al.; The nephrotoxic beta-lactam antibiotics (beta-lactams) cephaloridine, cephaloglycin and imipenem are toxic to the mitochondrial transport and (secondarily) oxidation of succinate and other dicarboxylic substrates . However, compared to cephaloglycin, cephaloridine is minimally toxic to the mitochondrial uptake and uncoupled oxidation of the short-chain fatty anion butyrate . Further studies were therefore done to compare the early effects of nephrotoxic doses (300 mg/kg body weight) of imipenem, cephaloridine and cephaloglycin on the mitochondrial metabolism of three important monocarboxylic substrates, butyrate, valerate and pyruvate, in rabbit renal cortex . The following was found: 1) imipenen reduces the oxidation of all three monocarboxylates, within 0.5 to 1 hr after administration . 2) The respiratory toxicity of cephaloglycin is essentially the same as that of imipenem with all three substrates . 3) cephaloridine causes little or no toxicity to pyruvate or butyrate oxidation and is significantly less toxic than imipenem or cephaloglycin to valerate oxidation . 4) The effects of the three beta-lactams on butyrate and pyruvate uptake parallel their effects on butyrate and pyruvate oxidation . CONCLUSIONS: Imipenem and cephaloglycin have essentially the same patterns of toxicity to the mitochondrial metabolism of all metabolic substrates that have been tested . Although cephaloridine has similar effects on dicarboxylic substrates, it is significantly less toxic to the mitochondrial metabolism of pyruvate and the short-chain fatty anions . It is proposed that cephaloridine's zwitterionic charge may restrict its ability to acylate monocarboxylic and other anionic carriers, resulting in less nephrotoxicity than might otherwise result from its uniquely high intracellular concentrations and singular ability among the toxic beta-lactams to produce oxidative injury.

J Thorac Cardiovasc Surg, 1995 Jul, 110(1), 224 - 38
A comparison of failure modes of glutaraldehyde-treated versus antibiotic-preserved mitral valve allografts implanted in sheep; Tamura K et al.; Morphologic studies and calcium analyses were made on mitral valve allografts from 12 juvenile sheep surviving 12 to 24 weeks after mitral valve replacement . Before implantation, the allografts were treated with 0.625% glutaraldehyde (group I, n = 4) or with cold antibiotic solution (group II, n = 8) . Three group I animals died 12 to 19 weeks after implantation because of dysfunction of calcified valves; the surviving animal also had extensive allograft calcification . One group II animal died of mitral regurgitation; the valves of the other seven (including five with regurgitation shown by Doppler and ventriculographic studies) were explanted at 19 to 24 weeks . Chordal rupture related to calcific deposits was found in all group I valves . Leaflet perforations (n = 4) and ruptured chordae (n = 4), each caused by connective tissue deterioration, were found in group II valves . Inflammatory reaction was absent or minimal in group I valves but moderate or severe in group II valves . Fibrous sheaths were thicker in group II than in group I valves . Calcium levels were much higher in group I than in group II valves . Calcification in group I valves was diffuse and involved collagen, elastic fibers, and connective tissue cells and matrix; in group II valves, it was localized in connective tissue cells . Thus glutaraldehyde-treated allografts failed because of extensive calcification, whereas antibiotic-preserved allografts underwent deterioration of connective tissue and infiltration by inflammatory cells.

J Med Microbiol, 1995 Jul, 43(1), 37 - 44
Dexamethasone treatment of lipopolysaccharide-induced meningitis in rabbits that mimics magnification of inflammation following antibiotic therapy; Rooney P et al.; The objective of adjunct anti-inflammatory therapy of bacterial meningitis is the containment of heightened inflammation caused by lysis of bacteria by antibiotics . This can be modelled by giving two consecutive intra-cisternal injections of lipopolysaccharide (LPS) to rabbits, the first at 0 h to induce inflammation to mimic that occurring during the proliferation of bacteria in the cerebrospinal fluid (CSF), and the second at 6 h to mimic inflammation subsequent to antibiotic-induced bacterial lysis . Injection of 2.5 ng of LPS induced pleocytosis at 4 h which was preceded by a peak of tumour necrosis factor (TNF) activity at 2 h . A subsequent injection of 25 ng of LPS at 6 h induced second peaks of pleocytosis and CSF TNF . Dexamethasone (1.5 mg/kg, i.v.) administered 15 min or 1 h before the second injection of LPS tended only to reduce CSF TNF, but effectively prohibited further pleocytosis . Brain TNF alpha mRNA levels were unchanged at 6 and 7 h after LPS injection, and were unaffected by dexamethasone . These results indicate that the subarachnoid space is distinct from the general circulation in that the TNF-producing cells present do not display a hypo-responsive state towards LPS as occurs when LPS is injected systemically . Furthermore, dexamethasone is able to attenuate the secondary inflammatory response resulting from a second LPS injection without eliminating a second peak of TNF activity.

Am J Emerg Med, 1995 Jul, 13(4), 396 - 400
Antibiotics to prevent infection of simple wounds: a meta-analysis of randomized studies; Cummings P et al.; A meta-analysis was conducted to determine whether prophylactic systemic antibiotics prevent infection in patients with nonbite wounds that are managed in the emergency department (ED) . A literature search was performed to identify published, randomized trials of prophylactic antibiotics for nonbite wounds . Blinded review of trial methods was used to select trials that randomly assigned patients to antibiotic or control groups and analyzed results by intention to treat . Of 9 randomized trials, 7 (with 1,734 study subjects) were accepted for analysis . The odds ratio for infection in treated patients compared with controls was used as the measure of effect, and a summary odds ratio was calculated . Patients treated with antibiotics had a slightly greater incidence of infection compared with untreated controls: odds ratio 1.16 (95% confidence interval {CI} 0.77 to 1.78) . Even among patients treated with a penicillinase-resistant antibiotic (5 trials with 1,204 patients), there was no benefit from treatment; odds ratio 1.00 (95% CI 0.59 to 1.71) . In conclusion, there is no evidence in published trials that prophylactic antibiotics offer protection against infection of nonbite wounds in patients treated in EDs.

J AOAC Int, 1995 Jul-Aug, 78(4), 978 - 86
Identification and measurement of beta-lactam antibiotic residues in milk: integration of screening kits with liquid chromatography; Harik-Khan R et al.; A procedure for identifying and quantitating violative beta-lactams in milk is described . This procedure integrates beta-lactam residue detection kits with the multiresidue automated liquid chromatographic (LC) cleanup method developed in our laboratory . Spiked milk was deproteinized, extracted, and subjected to reversed-phase LC using a gradient program that concentrated the beta-lactams . Amoxicillin, ampicillin, cephapirin, ceftiofur, cloxacillin, and penicillin G were, thus, separated into 5 fractions that were subsequently tested for activity by using 4 kits . beta-lactams in the positive fractions were quantitated by analytical LC methods developed in our laboratory . The LC cleanup method separated beta-lactam antibiotics from each other and from interferences in the matrix and also concentrated the antibiotics, thus increasing the sensitivity of the kits to the beta-lactam antibiotics . The procedure facilitated the task of identifying and measuring the beta-lactam antibiotics that may be present in milk samples.

J Vet Diagn Invest, 1995 Jul, 7(3), 374 - 9
Influence of the antibiotics lincomycin and tylosin on aflatoxicosis when added to aflatoxin-contaminated diets of growing swine; Harvey RB et al.; Effects of dietary aflatoxin (AF) and the antibiotics lincomycin (L) and tylosin (T) were evaluated in growing crossbred pigs . Six barrows (3 replicates of 2 each, mean body weight 14.0 kg) per group were assigned to 1 of 6 treatment groups (for a total of 36): 0 mg L, 0 mg T, and 0 mg AF/kg of feed (control); 220 mg L/kg of feed (200 g/ton); 110 mg T/kg of feed (100 g/ton); 2.5 mg AF/kg of feed; 2.5 mg AF plus 220 mg L/kg of feed; 2.5 mg AF plus 110 mg T/kg of feed . Barrows were administered their respective diets for 28 days . Body weight, body weight gain, and feed consumption were reduced by the AF alone, the AF plus L, and the AF plus T treatments, compared with control, L, and T treatments . Altered serum biochemical or hematologic measurements induced by AF treatments included increased serum activities of alkaline phosphatase and gamma-glutamyltransferase, increased hematocrit, hemoglobin, RBC count, WBC count, and mean cell hemoglobin, decreased serum concentrations of albumin, cholesterol, inorganic phosphorus, unsaturated iron binding capacity, total protein, and urea nitrogen, and decreased lymphoblastogenic response . Liver weight was increased, and microscopic lesions were consistent with those observed in cases of aflatoxicosis . With some other minor exceptions for hematologic and immunologic variables, these data indicate that the feed antibiotics lincomycin and tylosin, when added to aflatoxin-contaminated diets, do not have beneficial or detrimental effects on aflatoxicosis in growing swine.

New Microbiol, 1995 Jul, 18(3), 325 - 9
In vitro effects of novel glycopeptide antibiotics on the reactivity of the lipopolysaccharide (LPS) of S . minnesota R595; Matera G et al.; Four novel glycopeptide antibiotics, namely MDL 62708, MDL 63155, MDL 62827, MDL 62873 (mideplanin), plus teicoplanin, which differ in their chemical structure, were used to examine the relationship between the structure of glycopeptides and their LPS neutralization activity . Compound MDL 62708 (100 micrograms/ml) significantly reduced (P < 0.01 vs . antibiotic-free LPS, by Fisher's PLSD Test) metachromatic reactivity of S . minnesota R595 LPS (500 micrograms/ml) as evaluated by the DMB test . The remaining glycopeptides showed a significant reduction of the metachromatic reactivity, although at concentrations (333 and 1000 micrograms/ml) higher than MDL 62708 . Data obtained with LAL test appeared in accordance with those of the other techniques: all the glycopeptides used (100 and 1000 micrograms/ml) significantly (P < 0.05) reduced the reactivity of S . minnesota R595 LPS (50 pg/ml), and the lowest concentration of MDL 62708 (10 pg/ml) used produced a substantial, although not significant, reduction of the LPS reactivity with LAL . The antibiotic/LPS ratios associated to a significant reduction of LPS reactivity were 3.3/5 (wt/wt) and 2/1 (wt/wt) for DMB and LAL tests respectively . Such ratio appeared to be even lower for MDL 62708 . In conclusion, the four new glycopeptides, when tested at an antibiotic/LPS ratio about 1000 times lower than that which can be found in vivo, were able to reduce the reactivity of LPS in the in vitro models used . Teicoplanin aglycone MDL 62708, which also lacks the teicoplanin fatty acid, seems to have the same anti-LPS activity as the parental antibiotic, thus suggesting an important role for the glycopeptide backbone and NH2 groups in LPS-neutralizing effect.

Rev Med Brux, 1995 Jul-Aug, 16(4), 320 - 4
{Health economics and antibiotic therapy}; Leclercq P et al.; In the field of antibiotic therapy, particularly the methods of economic evaluation hold one's attention within the wide range of health economics' applications . Several tools allow a comparison of the outcomes of alternative strategies and thereby guide choices to the most appropriate solutions . After a brief recall of the methods classically used to evaluate health care strategy, the authors stress the importance and difficulty of fixing and applying a correct and satisfactory procedure for evaluation . An evaluation example of antibiotic therapy allows to illustrate the application of the principles confronting a field in which competition is intense and economic stakes stay large--a fact which naturally yields to seek after objective decision making criteria . The health care policies drawn by public authorities as well as the marketing strategies of the health sector trade are partly based on such evaluations . If these techniques are not intended for the practitioner in the first place, they should not be indifferent to him since they influence health authorities and thereby indirectly affect the therapeutic freedom of the physician.

Arch Biochem Biophys, 1995 Jun 20, 320(1), 177 - 81
The influence of antibiotics and antitumor agents on the relaxation activity of Pisum sativum leaf chloroplast topoisomerase I; Zagariya AM et al.; DNA topoisomerase was isolated from pea leaf chloroplasts . The relaxation activity of this topoisomerase was Mg2+ dependent and sensitive to ethidium bromide and novobiocin, a gyrase inhibitor . Chloroplast topoisomerase (Topo I) was ATP independent, as shown by the characteristic gel distribution of topoisomers . Topoisomerase, compared with the known eucaryotic topoisomerase I, was not stimulated by polyamines as are spermidine, spermine, and cadaverine . Ethidium bromide, DAPI, heparin, nalidixic acid, and m-AMSA (but not camptothecin) were able to inhibit the relaxation activity of chloroplast topo I . Nalidixic acid, novobiocin, m-AMSA, camptothecin, and amiloride were tested for their effects on the topoisomerase-catalyzed "cleavage complex" between DNA and chloroplast DNA topoisomerase I.

Antibiot Khimioter, 1995 Jun, 40(6), 3 - 6
{Induction of antibiotic formation by inactive cultures of actinomycetes . A mutant strain of Streptomyces helvaticus, a new producer of bruneomycin}; Malkina ND et al.; After exposure of an inactive actinomycete to ethidium bromide a stable mutant producing an antibiotic on a solid medium was isolated . The exposure to methylnitrosoguanidine provided the isolation of a more productive variant synthesizing the antibiotic in a liquid medium . By UV, IR, NMR and mass spectroscopy the antibiotic was identified as bruneomycin (streptonigrin) . The taxonomic investigation of the culture showed that it belongs to Streptomyces helvaticus which is a new culture producing bruneomycin (streptonigrin) . Previously it did not synthesize the antibiotic.

Pathol Biol (Paris), 1995 Jun, 43(6), 524 - 8
{The particular case of azalides: antibiotic diapedesis . Experimental data from a murine model of pneumococcal pneumonia}; Veber B et al.; The relations between the clinical efficacy, phagocytic transport phenomena, tissular and sera kinetics have been assessed in a pneumonia murine model . At first, the correlation between the clinical efficacy and pharmacokinetics characteristics has been studied for the erythromycin, spiramycin, roxithromycin, clarithromycin and azithromycin . An in vivo clinical efficacy hierarchy has been established (azi > ery > roxi = azi > spira) . A hierarchy identical to the clinical efficacy, has been recognised for the pulmonary elimination half lives and the pulmonar AUC . These could be considered as predictive of these antibiotics activity in the respiratory infections . In a second time, the tissular pharmacokinetics of the azithromycin in leukopenic mice allowed to confirm the leukocytes role in the transport and release of this antibiotic in the midst of the infections site . Finally, this antibiotic demonstrated its efficacy in a bacterienic infection even when administered at a low dosage thus allowing to have sera concentrations identical to those obtained in human clinical case and close to MIC's for S . pneumoniae . The pharmacokinetic novelty displayed by its strong tissular penetration can explain its remarkable efficacy.

Appl Environ Microbiol, 1995 Jun, 61(6), 2302 - 7
Overexpression of the robA gene increases organic solvent tolerance and multiple antibiotic and heavy metal ion resistance in Escherichia coli; Nakajima H et al.; Escherichia coli K-12 OST3410 was isolated previously as a stable cyclohexane-tolerant mutant derived from cyclohexane-sensitive strain JA300 . A plasmid which provides cyclohexane tolerance to strain JA300 was isolated from the OST3410 genomic library . Subcloning and sequence analysis showed that the plasmid contained the robA gene, whose gene product was reported to bind specifically to the right border of oriC . We observed that the robA gene on the multicopy plasmid generally increased the organic solvent tolerance of several E . coli strains . We also observed an increase in the organic solvent tolerance of JA300 carrying the lac-robA fusion gene on a low-copy plasmid by isopropyl-beta-D-thiogalactopyranoside induction . Strain JA300 carrying the multicopy robA plasmid also showed an increase in resistance to a number of unrelated antibiotics and heavy metal ions, and the spectrum of resistance was significantly similar to that of the soxS-overexpressing strain.

J Bacteriol, 1995 Jun, 177(11), 3323 - 5
The peptide antibiotic microcin 25 is imported through the TonB pathway and the SbmA protein; Salomon RA et al.; Selection of spontaneous mutants for insensitivity to the peptide antibiotic microcin 25 led to the isolation of five categories of mutants . Phenotypic and mapping studies showed the mutations to be located in the fhuA, exb, tonB, and sbmA genes . The latter encodes a cytoplasmic membrane protein which is also required for the penetration of microcin B17.

J Antibiot (Tokyo), 1995 Jun, 48(6), 484 - 7
Production of the new antibiotic tetrahydrokalafungin by transformants of the kalafungin producer Streptomyces tanashiensis; Kakinuma S et al.; The new antibiotic tetrahydrokalafungin was produced by the transformants of kalafungin producing S . tanashiensis and kalafungin-nonproducing mutants carrying the recombinant plasmid pKU523 . This plasmid consists of pKU501 (J . Antibiotics 44: 995 approximately 1005, 1991) which contains the gene cluster for kalafungin biosynthesis, and additional 5 kb stability region of SCP2*.

J Antibiot (Tokyo), 1995 Jun, 48(6), 471 - 8
Thiazinotrienomycins, new ansamycin group antibiotics; Hosokawa N et al.; New triene-ansamycins designated thiazinotrienomycins A, B, C, D and E were isolated from culture broth of Streptomyces sp . MJ672-m3 for their activities against cervical cancer cell lines . The structures and some biological and biochemical properties of the antibiotics were determined.

Fam Pract, 1995 Jun, 12(2), 166 - 70
Antibiotic use in upper respiratory tract infections in New Zealand; McGregor A et al.; Upper respiratory tract infections (URTIs) are a common reason for presentation to general practitioners . The current study used computerised consultation records of 100,222 patients from 17 general practices in New Zealand for the 12-month period 1 July 1991-30 June 1992 . URTIs were noted in 8.9% of all consultations: 44.1% of cases were children aged less than 10 years . Females presented more frequently than males for all ages above five years . Fifteen different antibiotics were prescribed for URTIs, but in 22.5% of cases no antibiotic was prescribed . There was no statistically significant difference in the likelihood of a successful outcome with or without antibiotic therapy (chi 2 = 0.76, P > 0.05) . The treatment failure profile of some antibiotics highlights the need for more prescriber education, especially as the range of medications available for general practitioner prescribing increases.

Antimicrob Agents Chemother, 1995 Jun, 39(6), 1292 - 4
Evaluation of antibiotic therapies for eradication of Helicobacter hepaticus; Foltz CJ et al.; The newly recognized murine pathogen Helicobacter hepaticus is known to colonize the ceca and colons of several strains of mice from a variety of commercial suppliers . Additionally, the organism persistently infects mice, causes a chronic hepatitis, and is linked to hepatic tumors in the A/JCr inbred mouse strain . For this reason, eradication of the organism from infected mouse colonies is desirable . Treatment modalities for eradication of H . hepaticus from the gastrointestinal system consisted of oral administration of various antibiotic combinations previously evaluated for eradication of experimental H . felis gastric infection in mice . A/JCr mice (8 to 10 weeks old) naturally infected with H . hepaticus were divided into six treatment groups of 10 animals each . Animals received monotherapy of amoxicillin, metronidazole, or tetracycline or triple therapy of amoxicillin-metronidazole-bismuth (AMB) or tetracycline-metronidazole-bismuth (TMB) . All medications were administered by oral gavage three times daily for 2 weeks . One month after the final treatment, mice were euthanatized and livers, ceca, and colons were cultured for H . hepaticus . All untreated control animals had H . hepaticus isolated from the cecum and/or colon . H . hepaticus was not recovered from the livers, ceca, or colons of the AMB or TMB treatment groups . All animals receiving the various antibiotic monotherapies had H . hepaticus isolated from the cecum and colon . We conclude that at the doses and the route evaluated, AMB and TMB triple therapies are effective for eradication of H . hepaticus in 8- to 10-week old A/JCr mice.

Kansenshogaku Zasshi, 1995 Jun, 69(6), 684 - 95
{Therapeutic evaluation of combination therapy using human native immunoglobulin preparation for i.v . administration, with antibiotics and G-CSF in severe infections in the field of internal medicine}; Kitamura K et al.; A human native immunoglobulin liquid preparation for intravenous injection, was used in combination with antibiotics and G-CSF to study its efficacy and safety in 49 patients with severe infections (Granulocyte counts were <or= 1000/ microliters, Body temperature was >or= 38 degrees C) which had not responded to antibiotic and G-CSF therapy of a 3-day or more duration . As a result of the Committee judgment, 49 patients were included in this study; 30 (61.7%) were included in efficacy and safety analysis . The analysis of 30 patients consisted of 9 patients (30.0%) with suspected septicemia, 5 (16.7%) with pneumonia, and 4 (13.3%) with septicemia . All patients had severe underlying diseases such as leukemia and malignant lymphoma . Clinical efficacy of Immunoglobulin preparation was judged by the doctors in charge to be "excellent" and "good" in 70.0% of the total cases . The rate of effectiveness was calculated from the results of the Committee judgment was 83.3% when "excellent" and "good" cases were included . No side effects were observed in all cases . Our results suggest that the immunoglobulin in combination with G-CSF is very effective on patients with severe infections.

Nucleic Acids Res, 1995 May 11, 23(9), 1524 - 30
Novel DNA photocleaving agents with high DNA sequence specificity related to the antibiotic bleomycin A2; Kuroda R et al.; We have designed and synthesized a series of novel DNA photocleaving agents which break DNA with high sequence specificity . These compounds contain the non-diffusible photoactive p-nitrobenzoyl group covalently linked via a dimethylene (or tetramethylene) spacer to thiazole analogues of the DNA binding portion of the antibiotic bleomycin A2 . By using a variety of 5' or 3' 32P-end labeled restriction fragments from plasmid pBR322 as substrate, we have shown that photoactive bithiazole compounds bind DNA at the consensus sequence 5'-AAAT-3' and induce DNA cleavage 3' of the site . Analysis of cleavage sites on the complementary DNA strand and inhibition of DNA breakage by distamycin A indicates these bithiazole derivatives bind and attack the minor groove of DNA . A photoactive unithiazole compound was less specific inducing DNA breakage at the degenerate site 5'-(A/T)(AA/TT)TPu(A/T)-3' . DNA sequence recognition of these derivatives appears to be determined by the thiazole moiety rather than the p-nitrobenzoyl group: use of a tetramethylene group in place of a dimethylene spacer shifted the position of DNA breakage by one base pair . Moreover, much less specific DNA photocleavage was observed for a compound in which p-nitrobenzoyl was linked to the intercalator acridine via a sequence-neutral hexamethylene spacer . The 5'-AAAT-3' specificity of photoactive bithiazole derivatives contrasts with that of bleomycin A2 which cleaves DNA most frequently at 5'-GPy-3' sequences . These results suggest that the cleavage specificity exhibited by bleomycin is not simply determined by its bithiazole/sulphonium terminus, and the contributions from other features, e.g . its metal-chelating domain, must be considered . The novel thiazole-based DNA cleavage agents described here should prove useful as reagents for probing DNA structure and for elucidating the molecular basis of DNA recognition by bleomycin and other ligands.

Arch Intern Med, 1995 May 8, 155(9), 922 - 8
Costs of duodenal ulcer therapy with antibiotics; Sonnenberg A et al.; BACKGROUND: Intermittent or maintenance therapy with histamine2 antagonists, highly selective vagotomy, or antibiotic therapy to eradicate Helicobacter pylori all represent distinct, viable options to manage duodenal ulcer disease . Comparing the costs associated with these four approaches could help in deciding among them . METHODS: The decision model of a Markov chain was used to compare the costs of the four approaches and their influence on the natural course of duodenal ulcers . Direct costs were calculated from the average wholesale prices of drugs and from charges for medical services submitted to and allowed by the Health Care Financing Administration . Average annual income was used to estimate indirect costs . RESULTS: The model predicted that after antibiotic therapy, 99.7% of patient time is spent free of duodenal ulcer . The corresponding percentages were 96.6% for maintenance therapy, 94.4% for vagotomy, 89.4% for intermittent therapy, and 82.8% without therapy . For an individual patient after 15 years, the expected total costs of a treatment approach involving antibiotics are $995, compared with $10,350 for intermittent therapy with histamine2 antagonists, $11,186 for maintenance therapy with histamine2 antagonists, and $17,661 after vagotomy . Incorporating upper gastrointestinal tract endoscopy to verify eradication of H pylori raises the costs of the antibiotic therapy option to $2426 . Increasing the annual infection rate of H pylori from baseline 1% to 10% raises the expected costs after 15 years to $3431 . Decreasing the H pylori eradication rate from baseline 80% to 50% raises the costs to $2679 . CONCLUSIONS: Compared with other options, antibiotics to eradicate H pylori are the cheapest therapy for duodenal ulcer and provide the least time spent with an active ulcer . From an economic perspective, antibiotics represent the treatment of choice.

Acta Pol Pharm, 1995 May-Jun, 52(3), 187 - 92
Electrochemical studies of some quinolone antibiotics . Part I . Qualitative analysis on mercury and carbon electrodes; Warowna-Grzeskiewicz M et al.; Direct current polarography and cyclic voltammetry was used to study quinolone antibiotics: ciprofloxacin, enoxacin, norfloxacin, ofloxacin and pefloxacin on a mercury and carbon electrode . The dependence of limiting currents and half-wave potentials on the pH of the solution, mercury head, temperature, ionic strength of the solution, methyl cellulose concentration, scan rate and quinolone concentration was studied . The optimal parameters and background solutions have been chosen . It was concluded that on mercury electrode quinolones are reduced in two one-electron waves and the process of the reduction is accompanied by an acid-base equilibrium . An anodic peak observed on graphite electrode is probably caused by the oxidation of piperazine ring in the molecule.

Indian Pediatr, 1995 May, 32(5), 529 - 31
Routine antibiotic cover for newborns intubated for aspirating meconium: is it necessary?
Krishnan L, Nasruddin, Prabhakar P, Bhaskaranand N.
A retrospective analysis was performed on 215 babies to evaluate the incidence of septicemia in babies intubated at birth for aspirating meconium from the trachea . Only term, appropriate for gestational age babies were included . Babies with any known perinatal risk factor for infection were excluded from the study and none of the babies had been put on "prophylactic antibiotics." There were 88 babies in the intubated group in a one year period from January 1991 to December 1991 . One hundred and twenty seven babies were taken as controls . There was no significant difference in the incidence of early septicemia in the two groups . There were no deaths in either group . It is concluded that well term babies who are intubated for aspirating meconium need not be put on routine antibiotic cover.

Antibiot Khimioter, 1995 May, 40(5), 35 - 7
{The possibility for obtaining sorbents from the mycelial wastes of antibiotic production}; Iakubova AR et al.; A technological process for production of a sorbent based on the mycelial waste of penicillin manufacture was developed . The process and its parameters are described . The exploitation conditions determine whether a strong sorbent with low sorption properties or a sorbent with higher sorption properties and lower granule strength is prepared.

J Antibiot (Tokyo), 1995 May, 48(5), 391 - 8
Structures and absolute configurations of antibiotics of the oligosporon group from the nematode-trapping fungus Arthrobotrys oligospora; Anderson MG et al.; Spectroscopic data define the structures of three new antibiotics, 4',5'-dihydro-oligosporon (4), hydroxyoligosporon (5) and 10',11'-epoxyoligosporon (6) from the nematode-trapping fungus Arthrobotrys oligospora, and confirm the structures of the recently reported antibiotics oligosporon (1) and oligosporol B (3) . The absolute configuration of the substituted 7-oxabicyclo{4.1.0}hept-3-ene nucleus of these metabolites is determined by circular dichroic spectroscopy . Oligosporon (1) and its dihydro-derivative (4) represent the second and most complex structural type of nematocidal metabolite to be characterised from cultures of nematophagous fungi.

Laryngoscope, 1995 May, 105(5 Pt 1), 472 - 4
Safety of ototopical antibiotics; Welling DB et al.; A prospective randomized study analyzing the safety and efficacy of a single dose of ototopical antibiotics following human middle ear tympanostomy tube insertion was performed . Fifty children undergoing bilateral tympanostomy tube insertion were studied by the placement of 0.5 mL of Cortisporin Otic Suspension (COS; Burroughs Wellcome Co., Research Triangle Park, N.C.) to one middle ear space by random assignment . Preoperative and postoperative audiograms were obtained, and the presence of otorrhea was noted . In one patient sensorineural hearing loss of 6 dB developed bilaterally, which was symmetric in both the treated and the untreated ear . This preliminary study showed no statistical difference in hearing loss or postoperative otorrhea associated with a single application of Cortisporin to the middle ear space.

Med Clin North Am, 1995 May, 79(3), 463 - 76
Antibiotic formulary selection; Crowe HM et al.; Physicians worldwide are being forced to consider economics in the care of patients . In most hospitals, antibiotics are a steadily increasing segment of the pharmacy budget . This article discusses how the authors used drug pharmacokinetics, restriction policies, and cost benefit analysis to design a cost-effective antibiotic formulary.

FEMS Microbiol Lett, 1995 May 1, 128(2), 101 - 6
Effect of the lipopeptide antibiotic, iturin A, on morphology and membrane ultrastructure of yeast cells; Thimon L et al.; The effects of iturin A, at fungicidal concentrations, on yeast cells were studied by scanning electron microscopy and by transmission electron microscopy . A depression, observed in each iturin A-treated cell, was the consequence of the release of electrolytes and other cytoplasmic components . Iturin A passes through the cell wall and disrupts the plasma membrane with the formation of small vesicles and the aggregation of intramembranous particles . Moreover, iturin A passes through the plasma membrane and interacts with the nuclear membrane and probably with membranes of other cytoplasmic organelles.

Therapie, 1995 May-Jun, 50(3), 243 - 5
{Drug interactions and antibiotics}; Jourdan J et al.; Situations that require the use of systemic antibiotic therapy are common and drug interactions are potentially frequent . These interactions may be deleterious and lead to reduction of therapeutic index, enhancement of toxic risk or may be favourable, with optimization of pharmacokinetics or pharmacodynamics . The mechanisms of these interactions are discussed.

Br Poult Sci, 1995 May, 36(2), 265 - 75
Influence of dietary enzyme complex on the performance of broilers fed on diets with and without antibiotic supplementation; Vranjes MV et al.; 1 . The aim of the experiment was to test the possible interactions of an enzyme complex and a food antibiotic on the growth and metabolism, carcase yield, whole body composition and nutrient deposition in broilers . The basal diet contained 400 g/kg barley . The four treatments were as follows: O--without supplements (control), E--enzyme complex Roxazyme G, 200 mg/kg, A--antibiotic avoparcin, 10 mg/kg, EA--Roxazyme G, 200 mg/kg plus avoparcin, 10 mg/kg . 2 . Roxazyme G positively influenced weight gain, food conversion efficiency, energy metabolisability, fat and nitrogen utilisation and the dry matter content of droppings . Fat and energy deposition in the whole body were also increased, whereas protein deposition and carcase yield were not influenced . 3 . Avoparcin increased energy metabolisability and fat utilisation, but had no influence on nitrogen utilisation . No significant improvements from avoparcin were seen in growth or in nutrient deposition in the body . The fibre degradability (NDF and ADF fraction) was significantly depressed by antibiotic supplementation . 4 . The inclusion of both supplements to the diet did not have a fully additive effect on growth, energy metabolisability, or fat and nitrogen utilisation . The interaction between enzyme and antibiotic for food conversion efficiency during the first experimental period (7 to 21 d) was nearly significant (P = 0.053) . Except for fibre degradability (P < or = 0.01), no other significant interactions between enzyme and antibiotic were found.

Int J Clin Pharmacol Ther, 1995 May, 33(5), 266 - 76
Pharmacokinetic development of quinolone antibiotics; Schaefer HG et al.; A prerequisite for the pharmacokinetic development of quinolone antibiotics is a sensitive and accurate method for the quantification of the drug in biological fluids . Both, a drug specific (e.g . HPLC) and a drug non-specific but effect related assay (e.g . bioassay) should be used during early clinical development to detect major active metabolites . The basic pharmacokinetic behavior of the drug is investigated as part of the early phase I program, where single and multiple ascending dose studies are performed to characterize the safety and tolerability of the quinolone in healthy volunteers . Further pharmacokinetic studies are performed to describe the absolute bioavailability, dose proportionality, pharmacokinetics in young and elderly, male and female volunteers . The suitability of the clinical dosage from must be evaluated in comparison to an oral solution and by quantification of the effect of food on bioavailability . The characterization of the absorption in different parts of the gastrointestinal tract may be valuable for dosage form optimization . In order to start phase IIb clinical trials, the potential of possible drug-drug interactions with antacids, cimetidine, theophylline and warfarin has to be evaluated . This can be done by in vitro and in vivo preclinical experiments, before formal clinical-pharmacology studies are performed . Further pharmacokinetic characterization (e.g . studies in special subpopulation, extended interaction studies, total recovery using 14C-labelled compound, blister fluid penetration) will be done parallel to the phase II/III development program . During these efficacy and safety trials blood samples should be obtained and PK-parameters can be calculated using sparse data analysis methods like non-linear mixed effect modeling (NONMEM) or Bayesian methods to characterize the pharmacokinetics in the target population.

Vnitr Lek, 1995 May, 41(5), 332 - 5
{Ambulatory parenteral antibiotic therapy}; Pospisilova Y; The paper sums up the current knowledge on the outpatient parenteral antibiotic therapy, the information is based on the experience with this type of treatment in the USA . The introduction gives the reasons for outpatient as opposed to inpatient therapy . The first part of the paper discusses the indications and the contraindications of outpatient parenteral antibiotic therapy, the choice of the adequate antibiotic, the organisation of this treatment and the cooperation between the doctors, nurses and patients . The second part of the paper deals with specific diseases and the possibility of their treatment by means of outpatient parenteral antibiotic therapy.

Urol Nefrol (Mosk), 1995 May-Jun, (3), 11 - 4
{Tubular interstitial disorders in the nephrotoxic action of antibiotics}; Potapova AV et al.; Experimental and clinical evaluation of antibiotic nephrotoxicity suggest a conclusion that these drugs may cause tubular damage in relatively unaffected function of tubular apparatus . Progression of tubular dysfunction results from accumulation of high concentrations of antibiotics in renal parenchyma due to tubular filtration and secretion of the drug by tubular epithelium cells . In the majority of patients the disease manifestations were directly associated with antibiotics administration . Tubular dysfunctions present as concentration, acid-excretion, glucose transport and beta 2-microglobulin reabsorption abnormalities . Though renal lesions proved benign, there were occasional cases of acute renal insufficiency in the absence of arterial hypertension.

J Antimicrob Chemother, 1995 May, 35(5), 669 - 74
Quantitation of antibiotic effects on bacteria by bioluminescence, viable counting and quantal analysis; Soren L et al.; Discrepant results are obtained when antibiotic-induced bacterial killing is quantitated by viable counting or bioluminescence assay of intracellular ATP . In this study the killing of bacteria exposed to amikacin or imipenem was quantitated by viable counting and bioluminescence assay of intracellular ATP and also by quantal analysis . The results of quantal analysis and viable counting agreed very well, whereas a much lower degree of bacterial killing was recorded by bioluminescence.

Drug Metab Dispos, 1995 May, 23(5), 542 - 7
The antibiotic tiamulin is a potent inducer and inhibitor of cytochrome P4503A via the formation of a stable metabolic intermediate complex . Studies in primary hepatocyte cultures and liver microsomes of the pig; Witkamp RF et al.; Tiamulin is a semisynthetic antibiotic frequently used in agricultural animals . The drug has been shown to produce clinically important--often lethal--interactions with other compounds that are simultaneously administered . To explain this, it has been suggested that tiamulin selectively inhibits oxidative drug metabolism via the formation of a cytochrome P450 metabolic intermediate complex . The aim of the present study was to provide further support for this hypothesis . When hepatic microsomes and cultured primary pig hepatocytes were incubated with tiamulin, a maximum in the absorbance spectrum at 455 nm was observed, which disappeared after adding KFe(CN)6 . When hepatocytes were incubated with tiamulin for 72 hr, cytochrome P450 content and cytochrome P4503A apoprotein levels were increased . Tiamulin strongly inhibited and concentration dependently inhibited the hydroxylation rate of testosterone at the 6 beta-position in both microsomes and hepatocytes, and the microsomal N-demethylation rate of ethylmorphine . Other testosterone hydroxylations were inhibited to a lesser extent or not affected . The relative inhibition of the hydroxylation of testosterone at the 6 beta-position was more pronounced in microsomes from rifampicin- and triacetyloleandomycin-treated pigs . The results indicate that cytochrome P450 complex formation can at least partly explain the interactions observed with tiamulin . Tiamulin seems to be a strong, probably selective, inhibitor of the cytochrome P4503A subfamily and an interesting tool for further research.

Mol Microbiol, 1995 May, 16(3), 385 - 95
Beta-lactamases and bacterial resistance to antibiotics; Frere JM; The efficiency of beta-lactam antibiotics, which are among our most useful chemotherapeutic weapons, is continuously challenged by the emergence of resistant bacterial strains . This is most often due to the production of beta-lactamases by the resistant cells . These enzymes inactivate the antibiotics by hydrolysing the beta-lactam amide bond . The elucidation of the structures of some beta-lactamases by X-ray crystallography has provided precious insights into their catalytic mechanisms and revealed unsuspected similarities with the DD-transpeptidases, the bacterial enzymes which constitute the lethal targets of beta-lactams . Despite numerous kinetic, structural and site-directed mutagenesis studies, we have not completely succeeded in explaining the diversity of the specificity profiles of beta-lactamases and their surprising catalytic power . The solutions to these problems represent the cornerstones on which better antibiotics can be designed, hopefully on a rational basis.

Acta Gastroenterol Belg, 1995 May-Aug, 58(3-4), 290 - 6
Hepatotoxicity of antibiotics; Hautekeete ML; Several antibiotics can cause severe hepatic injury . It is the purpose of this paper to review the main antibiotics that can cause hepatic injury and discuss the presentation, pattern, and outcome of hepatic injury . In the case of the penicillins, the combination amoxycillin-clavulanate and the penicillinase-resistant penicillins oxacillin, (di-)cloxacillin, and flucloxacillin can cause (mainly cholestatic) hepatitis . Cephalosporins have little hepatotoxicity; ceftriaxone can cause drug-induced gallstones . The potential of erythromycin and several other macrolides to cause (usually cholestatic) hepatitis is well established . Tetracyclines can cause a syndrome mimicking acute fatty liver of pregnancy, but this complication has virtually disappeared . Quinolones seem to be able to cause cholestasis . Sulfamethoxazole/trimethoprim can cause severe hepatotoxicity, especially in patients with acquired immunodeficiency syndrome (AIDS) . Finally, nitrofurantoin can cause acute cholestatic and hepatocellular reactions as well as chronic hepatitis mimicking chronic auto-immune hepatitis.

Presse Med, 1995 Apr 29, 24(16), 750 - 2
{Critical serum concentration of antibiotics . A therapeutic tool and means of comparative evaluation}; Potel G et al.; It is difficult to predict the clinical activity of antibiotics solely on the basis of in vitro data . Experimental models measuring the relationship between serum concentration and in vivo activity are essential for comparing the activity of different compounds currently available . The critical serum concentration can be used to compare the intrinsic activity of antibiotics on a given bacterial strain . When compared with the minimal inhibiting concentration measured in vitro, "activity loss" can be determined for each antibiotic placed in contact with bacteria in an infected tissue . The relevance of this therapeutic tool in comparison with other methods is discussed.

Eur J Pharmacol, 1995 Apr 28, 289(2), 321 - 33
Aminoglycoside antibiotics induce aggregation but not fusion of negatively-charged liposomes; Van Bambeke F et al.; The binding of aminoglycoside antibiotics to acidic phospholipids of membranes is an essential step in the development of both their renal and auditory toxicities, which could be associated with critical modifications of the membrane properties . This work examines the capacity of aminoglycosides to induce membrane aggregation and fusion . Three techniques were used in parallel: (i) measurement of the dequenching rate of a lipid-soluble fluorescent probe (octadecylrhodamine B) incorporated at self-quenched concentration in membranes; (ii) measurement of the increase in the energy transfer between two fluorescent derivatives of phospholipids; and (iii) electron microscopy of negatively-stained replicas . The results were compared with those obtained with spermine (an aggregating polycation) and melittin (a fusogenic peptide) . The three approaches indicate that aminoglycosides induce liposomes aggregation, but not fusion . Aggregation is related to the capacity of each drug studied to bind phosphatidylinositol, as evaluated by its energy of interaction with this acidic phospholipid, and to its toxic potential . Membrane aggregation occurring in vivo could therefore contribute to, or be a determinant of this toxicity, which could rationally be screened for new derivatives by the methods applied here.

Microb Drug Resist, 1995 Spring, 1(1), 5 - 8
Antibiotic-resistant pneumococci in pediatric disease; Klugman KP et al.; The surveillance of pneumococcal resistance in nasopharyngeal isolates is a practical way to determine the prevalence of resistant strains and is a reasonable predictor of resistance in systemic isolates . The increasing prevalence of resistance is shifting the distribution of invasive pneumococcal serotypes toward those included in conjugate vaccines . If these vaccines reduce carriage, they may eliminate or greatly reduce the prevalence of resistant strains . Meningitis is the most important infection caused by PRP for which penicillin or ampicillin therapy is inappropriate . Although the extended spectrum cephalosporins will be effective for most cases of PRP meningitis, it is clear that such therapy is not foolproof . It is important for the laboratory to test CSF isolates not only for penicillin resistance but also for resistance to the cephalosporins . beta-Lactam antibiotics can still be considered appropriate empiric therapy for otitis media, pneumonia, or sepsis . However, occasional treatment failures with these agents may necessitate use of alternative therapeutic strategies.

Bioorg Med Chem, 1995 Apr, 3(4), 429 - 36
On the conformation of Phe78 of a chromoprotein antibiotic, neocarzinostatin; Imajo S et al.; A structure of neocarzinostatin, an antitumor chromoprotein antibiotic, has been built using X-ray crystallographic data and NMR data, particularly NOE data observed between the apoprotein and the chromophore . Chemical shift changes of protons of the chromophore upon binding to the apoprotein indicated that the aromatic plane of Phe52 has the conformation almost perpendicular to the C-2-C-3 triple bond of the core of the chromophore while Phe78 takes multiple conformations in solution although one of the stable conformations has been assigned for Phe78 in a crystal structure.

Br J Rheumatol, 1995 Apr, 34(4), 380 - 2
Role of prophylactic antibiotics in the prevention of late infection of prosthetic joints . Results of a questionnaire and review of the literature; Averns HL et al.; A postal survey has revealed wide variation in attitudes towards the need for prophylactic antibiotics in patients with implants who develop intercurrent infections, or who undergo surgical procedures . The available evidence is insufficient to reach any firm conclusions, however any patient who has an implant should receive swift treatment for intercurrent infections.

J Antibiot (Tokyo), 1995 Apr, 48(4), 293 - 9
RS-22A, B and C: new macrolide antibiotics from Streptomyces violaceusniger . II . Physico-chemical properties and structure elucidation; Ubukata M et al.; RS-22A, B and C are novel 36-membered macrolide antibiotics produced by Streptomyces violaceusniger . The structures of these antibiotics were unambiguously determined by 1D and 2D NMR and tandem-mass analysis of the oxidative derivative of RS-22C.

Toxicol Lett, 1995 Apr, 76(3), 239 - 43
Correlation between in vitro and in vivo models of proconvulsive activity with the carbapenem antibiotics, biapenem, imipenem/cilastatin and meropenem; Day IP et al.; The present study evaluated the proconvulsant liability of biapenem, a novel carbapenem antibiotic, in in vitro and in vivo experiments, in comparison with the carbapenems, imipenem/cilastatin and meropenem . Imipenem/cilastatin is a carbapenem antibiotic with known proconvulsive liability in man and in animal experiments . In in vivo studies imipenem/cilastatin, at doses of 400/400 mg/kg i.v., significantly lowered the convulsive threshold of pentylenetetrazol (PTZ) in mice and shifted the dose-response curve of PTZ . The effects of biapenem (400 mg/kg i.v.) and another reference carbapenem, meropenem (400 mg/kg i.v.), in the mouse PTZ model were not significantly different from control . In in vitro experiments the carbapenems were tested for their ability to inhibit {3H}muscimol (1.3 mM) binding to rat brain homogenates at concentrations of 1-10 mM . Similar to in vivo results, when compared to imipenem/cilastatin, biapenem and meropenem did not inhibit {3H}muscimol binding to the GABAA receptor complex in brain homogenates while imipenem/cilastatin exhibited significant inhibition (IC50 = 4.6 mM) . These results further confirm the correlation between in vitro GABAA binding and in vivo PTZ convulsive testing with carbapenem antibiotics, and suggest that biapenem possesses a low proconvulsive liability.

J Allergy Clin Immunol, 1995 Apr, 95(4), 853 - 9
Effects of macrolide antibiotics on neurally mediated contraction of human isolated bronchus; Tamaoki J et al.; BACKGROUND: Long-term administration of macrolide antibiotic substances is an alternative therapy used in the treatment of asthma and airway hyperresponsiveness, but neither its mechanism of action nor whether this substance exerts an immediate action in the airways is known . METHODS: Contractile responses of human isolated bronchial strips to electrical field stimulation (EFS) and acetylcholine were assessed under isometric conditions in the absence and presence of erythromycin, roxithromycin, or clarithromycin . RESULTS: Incubation of tissues with erythromycin (3 x 10(-5) mol/L) attenuated the contractile responses to EFS so that the stimulus frequency required to produce 50% of the maximal contraction increased from 4.1 +/- 0.5 to 10.1 +/- 0.7 Hz (mean +/- SE; p < 0.001) . In contrast, contractile responses to acetylcholine were not changed . Erythromycin reduced the EFS-induced contraction in a concentration-dependent fashion; the maximal decrease from the baseline response was 92.8% +/- 3.6% (p < 0.001) . This inhibitory effect was not altered by propranolol, indomethacin, ouabain, charybdotoxin, or mechanical removal of the epithelium . Roxithromycin and clarithromycin likewise inhibited neurally mediated contraction . CONCLUSIONS: These results suggest that macrolides may inhibit cholinergic neuroeffector transmission in the human airway smooth muscle, probably by reducing exocytotic release of acetylcholine from the nerve terminals.

J Pharmacol Exp Ther, 1995 Apr, 273(1), 26 - 31
Functional expression of transporter for beta-lactam antibiotics and dipeptides in Xenopus laevis oocytes injected with messenger RNA from human, rat and rabbit small intestines; Tamai I et al.; A heterologous gene expression system, Xenopus laevis oocytes, was used to prove the intestinal absorption of various beta-lactam antibiotics mediated by an H(+)-dipeptide cotransport system in rat, rabbit and human small intestines . The microinjection of mRNA (messenger RNA) from rat intestine into Xenopus laevis oocytes led to significantly higher uptakes of p.o . active cephalosporins including zwitter-ionic derivatives (cephalexin, cephradine and cefadroxil) and dianionic derivatives (cefixime and ceftibuten) in comparison with oocytes injected with water, whereas the uptake of cefazolin, a parenterally administered derivative, was negligible in both mRNA- and water-injected oocytes . The uptake of cefadroxil was reduced significantly in the presence of dipeptide and various beta-lactam antibiotics, but not in the presence of an amino acid . After sucrose density gradient centrifugation of mRNA, the highest expression of transport activities of both cefadroxil and ceftibuten was observed in the same mRNA fraction with a size of 2.20 to 3.75 kilobases . mRNA-injected oocytes showed a marked pH-dependency in the uptakes of cefadroxil and ceftibuten, whereas water-injected oocytes exhibited only modes uptakes . The most stimulated uptakes of cefadroxil and ceftibuten were observed at an external pH of 5.5 and 5.0, respectively . Furthermore, injection of mRNA isolated from either rat rabbit or human small intestine into oocytes produced significantly higher uptake of cefadroxil and ceftibuten compared with those by oocytes injected with water . Thus, intestinal absorption of p.o . active beta-lactam antibiotics was confirmed to be mediated by an H+ gradient-dependent transport system across the brush-border membrane of rats, rabbits and humans . The carrier-protein for this process is likely a dipeptide transport system.

Arch Otolaryngol Head Neck Surg, 1995 Apr, 121(4), 445 - 8
Prophylactic antibiotic drops after tympanostomy tube placement; Hester TO et al.; OBJECTIVE: To evaluate the effectiveness of prophylactic polymyxin B sulfate-neomycin sulfate-hydrocortisone drops in decreasing the incidence of posttympanostomy otorrhea . DESIGN: Prospective randomized controlled study . SETTING: University referral center . PATIENTS: Three hundred patients undergoing tympanostomy tube placement (including those undergoing tonsillectomy, adenoidectomy, or both) were randomized into three groups . INTERVENTION: The use of polymyxin B-neomycin-hydrocortisone drops . Patients in group 1 received no antibiotic drops; group 2, a single dose intraoperatively, and group 3, an intraoperative dose followed by a 5-day course . MAIN OUTCOME MEASURE: Posttympanostomy otorrhea . RESULTS: A statistically significant decrease was observed in the incidence of posttympanostomy otorrhea between the control (16.4%) and treatment groups (group 2, 8.3%; group 3, 8.1%) (P = .011) . A single dose of antibiotics was effective when patients' middle ears were dry or had serous effusions . A 5-day course was indicated for those whose ears had mucoid or purulent contents . CONCLUSIONS: Antibiotic ear drops are indicated in all patients . A single dose is as effective as a 5-day course, but our data support a longer course in certain subgroups.

Pigment Cell Res, 1995 Apr, 8(2), 83 - 8
Effect of penicillin-streptomycin and other antibiotics on melanogenic parameters in cultured B16/F10 melanoma cells; Martinez-Liarte JH et al.; Penicillin and streptomycin, the most widely used antibiotics in mammalian cell cultures, caused a moderate stimulation in dopa oxidase and tyrosine hydroxylase activities, but a slight inactivation in the dopachrome tautomerase activity of B16/F10 melanoma cells at the routine concentration (100 units/ml penicillin and 100 micrograms/ml streptomycin) used for preventing bacterial growth in cultured animal cells . At these concentrations, tyrosinase activities and melanin content augmented with time during the first 24-48 hr . The opposite effect acted on cell viability . After withdrawal of the antibiotics from the culture medium, the recovery of melanogenic parameters to normal values was fully reached after few hours (around 10), and it was already noticeable as soon as 4 hr after removal . Other antibiotics used in cell culture, like kanamycin, gentamicin, and the antimicotic nystatin, exerted similar low effects at the recommended concentrations, always lower than two-fold and thus lower than those reported for amphotericin B . Taking into account these relatively low effects, and the high risk of contamination of mammalian cells culture without antibiotics, penicillin and streptomycin may still be routinely used in experiments leading to explore the melanogenic activity of malignant melanocytes in culture, unless very precise studies and strict conditions were needed.

Antibiot Khimioter, 1995 Apr, 40(4), 12 - 6
{Resistance to its own antibiotic nigericin and macromolecular synthesis in Streptomyces hygroscopicus 155}; Ivanova IV et al.; The influence of nigericin (nandavir) on the organism producing it (Streptomyces hygroscopicus 155) was studied with respect to the synthesis of protein, RNA and DNA . The resistance of the mycelium of different ages to the exogenic antibiotic was investigated . Exogenic nigericin had a more marked inhibitory effect on the macromolecular synthesis in a nonproductive variant of the strain . The antibiotic sensitivity of the mycelium in both the variants (productive and nonproductive) depended on the culture age . It was suggested that there were not less than two mechanisms of the protection from the own antibiotic in the organism.

Rozhl Chir, 1995 Apr, 74(3), 116 - 8
{New approaches in the use of antibiotics in the treatment of postoperative intra-abdominal infections}; Vyhnanek F et al.; The authors present the results of a clinical investigation on the therapeutic use of carbapenem, imipenem/cilastatin in 20 patients operated on account of intraabdominal inflammatory affections, hospitalized at the intensive care unit of the Surgical Clinic of the Third Medical Faculty, Charles University, Prague in 1993 . Imipenem/cilastatin was administered to patients during surgery--500 mg i.v.--and subsequently after 8--hour intervals for 5-8 days . During comprehensive treatment no superinfection developed and the patients recovered.

Clin Otolaryngol, 1995 Apr, 20(2), 100 - 2
Should prophylactic antibiotics be used in the management of cerebrospinal fluid rhinorrhoea following endoscopic sinus surgery? A review of the literature; Moralee SJ; This review article investigates whether prophylactic antibiotics should be used in the management of cerebrospinal fluid rhinorrhoea following endoscopic sinus surgery . A medline database was used to retrieve all English articles from 1970 to the present, cross-indexing cerebrospinal rhinorrhoea, antibiotics and endoscopic sinus surgery . All relevant articles retrieved were reviewed together with their bibliographies . The use of prophylactic antibiotics is neither recommended nor condemned by evidence of efficacy . However, their use is cautioned against by evidence of a subsequent change in nasopharyngeal flora to potentially more invasive organisms . The review concludes that, at present, it is usually justifiable to withhold prophylactic antibiotics and to observe for the symptoms and signs of meningitis instituting antibiotic therapy when this complication develops.

Ther Drug Monit, 1995 Apr, 17(2), 179 - 83
Quantitative determination of the antibiotic azithromycin in human serum by high-performance liquid chromatography (HPLC)-atmospheric pressure chemical ionization mass spectrometry: correlation with a standard HPLC-electrochemical method; Fouda HG et al.; A specific assay for the quantitative determination of the new antibiotic azithromycin in a low volume of human serum is described . The assay uses on-line high-performance liquid chromatography (HPLC) and atmospheric pressure chemical ionization mass spectrometry (HPLC-APCI) . Deuterium-labeled azithromycin was synthesized and used as the internal standard of the assay . The drug and the internal standard are extracted from 50 microliters of serum, and aliquots are injected onto a standard reverse-phase HPLC column . The effluent from the HPLC column at 1 ml/min is introduced into the atmospheric pressure source of a SCIEX API III mass spectrometer . Azithromycin concentrations in serum are determined by the selected monitoring of the protonated molecular ions of the drug and the internal standard . Our assay yields accurate and precise results over the range 10 ng/ml to 250 ng/ml . The correlation between the assay and a standard HPLC-electrochemical method, requiring a larger volume of serum, has been determined . The two methods showed excellent agreement . Because of its low volume requirement, our HPLC-APCI assay can be substituted for the standard assay for the investigation of azithromycin pharmacokinetics in children.

Chem Pharm Bull (Tokyo), 1995 Apr, 43(4), 689 - 92
Stability of a 1 beta-methylcarbapenem antibiotic, meropenem (SM-7338) in aqueous solution; Takeuchi Y et al.; The stability and the degradation products of 1 beta-methylcarbapenem, meropenem in aqueous solution were investigated . In pH 4-8 dilute solution, pseudo-first-order degradation was observed, and good stability of meropenem in aqueous solution was demonstrated by the effect of 1 beta-methyl group against hydrolysis of beta-lactam ring . As degradation products, the beta-lactam hydrolyzed product and the dimer product resulting from intermolecular aminolysis of beta-lactam ring by the amine of the second molecule were described.

Tohoku J Exp Med, 1995 Apr, 175(4), 289 - 92
Antibiotic pasting for foul putrefactive cancers; Okuyama S; Putrefaction of cancers in infrequent . Nonetheless, it presents a difficult clinical problem of foulness . We prepared 5% antibiotic pastes by adding sodium polyacrylate to aliquots of antibiotic solutions, and applied them to putrefactive lesions in 4 cases of rectal cancer, 2 of breast cancer and 1 of tongue cancer . The putrefaction was promptly brought under control in all of them, permitting an improved QOL . Concomitant application of anticancer pastes was also found remarkably effective . Use of sulperazone may offer a better chance of overcoming the beta lactamase barrier in cases of prolonged use.

Mol Microbiol, 1995 Apr, 16(2), 333 - 43
A second ABC transporter is involved in oleandomycin resistance and its secretion by Streptomyces antibioticus; Olano C et al.; A 3.2 kb Sstl-Sphl DNA fragment of Streptomyces antibioticus, an oleandomycin producer, conferring resistance to oleandomycin was sequenced and found to contain an open reading frame of 1710 bp (oleB) . Its deduced gene product (OleB) showed a high degree of similarity with other proteins belonging to the ABC-transporter superfamily including the gene product of another oleandomycin-resistance gene (OleC) . The OleB protein contains two ATP-binding domains, each of approximately 200 amino acids in length, and no hydrophobic transmembrane regions . Functional analysis of the oleB gene was carried out by deleting specific regions of the gene and assaying for oleandomycin resistance . These experiments showed that either the first or the second half of the gene containing only one ATP-binding domain was sufficient to confer resistance to oleandomycin . The gene oleB was expressed in Escherichia coli fused to a maltose-binding protein (MBP) using the pMal-c2 vector . The MBP-OleB hybrid protein was purified by affinity chromatography on an amylose resin and polyclonal antibodies were raised against the fusion protein . These were used to monitor the biosynthesis and physical location of OleB during growth . By Western analysis, the OleB protein was detected both in the soluble and in the membrane fraction and its synthesis paralleled oleandomycin biosynthesis . It was also shown that a Streptomyces albus strain, containing both a glycosyltransferase (OleD) able to inactivate oleandomycin and the OleB protein, was capable of glycosylating oleandomycin and secreting the inactive glycosylated molecule . It is proposed that OleB constitutes the secretion system by which oleandomycin or its inactive glycosylated form could be secreted by S . antibioticus.

Toxicology, 1995 Mar 31, 97(1-3), 225 - 34
Epitope mapping of beta-lactam antibiotics with the use of monoclonal antibodies; Mayorga C et al.; In order to evaluate the antigenic contribution of different regions of the penicillin molecule, monoclonal antibodies were raised against amoxicillin-protein conjugates and their specificities analysed in detail . A random sample of the clones produced was analysed by a quantitative inhibition-ELISA, using, as inhibitors, monomeric conjugates of the following antibiotics to butylamine (BA), amoxicillin (AX), ampicillin (AMP), benzylpenicillin (BP) and the nuclear part of these, 6-aminopenicillanic acid (6-APA); and different parts of the following molecules: N-(p-hydroxyphenyl)-glycine (PHPG), N-phenylglycine (NPG), phenylacetic acid (PA) and thiazolidine (TIAZ) . The results showed that 92% of the antibodies recognized an epitope in which the side chain was a major constituent, although with variable contributions from other regions of the molecule . There was a high degree of crossreactivity with aminopenicillins, but low or absent crossreactivity with BP . None of the antibodies recognized the thiazolidine ring or the conjugated nuclear region of the penicillins . Finally, one antibody seemed to recognize, equally, all the different structures tested . The possible relevance of these results to penicillin allergy is discussed.

Toxicology, 1995 Mar 31, 97(1-3), 19 - 22
The dental amalgam mercury controversy--inorganic mercury and the CNS; genetic linkage of mercury and antibiotic resistances in intestinal bacteria; Lorscheider FL et al.; Mercury (Hg) vapor exposure from dental amalgam has been demonstrated to exceed the sum of all other exposure sources . Therefore the effects of inorganic Hg exposure upon cell function in the brain and in the intestinal bacteria have recently been examined . In rats we demonstrate that ADP-ribosylation of tubulin and actin brain proteins is markedly inhibited, and that ionic Hg can thus alter a neurochemical reaction involved with maintaining neuron membrane structure . In monkeys we show that Hg, specifically from amalgam, will enrich the intestinal flora with Hg-resistant bacterial species which in turn also become resistant to antibiotics.

Chem Biol Interact, 1995 Mar 30, 95(1-2), 17 - 28
Comparison of the sequence selectivity of the DNA-alkylating pluramycin antitumour antibiotics DC92-B and hedamycin; Prakash AS et al.; The sequence selectivity of DNA alkylation by the recently isolated pluramycin antitumour antibiotic DC92-B has been investigated using two methods: a piperidine-induced strand-breaking procedure and a Taq DNA polymerase/linear amplification method . These techniques reveal that guanines are the most reactive sites for alkylation and that the level of adduct formation at these sites is clearly sequence dependent . The highest levels of alkylation occurred at isolated guanines located in 5'-CGT sequences and also at the 5'-G in some 5'-CGG sequences . Isolated guanines in 5'-TGT sequences were also quite reactive . We have also re-examined, in parallel, the sequence selectivity of binding of the structurally-related compound hedamycin: the first known example of a bis(epoxide)-containing, DNA-alkylating pluramycin . Our studies included a more extensive sequence analysis of hedamycin binding than that previously reported and we are able, therefore, to define more precisely the sequence preference . Despite significant differences in the stereochemistry and substitution of their bis(epoxide) sidechains, hedamycin and DC92-B exhibited very similar sequence selectivities in our assays.

Nucleic Acids Res, 1995 Mar 25, 23(6), 885 - 92
Transferring the purine 2-amino group from guanines to adenines in DNA changes the sequence-specific binding of antibiotics; Bailly C et al.; The proposition that the 2-amino group of guanine plays a critical role in determining how antibiotics recognise their binding sites in DNA has been tested by relocating it, using tyrT DNA derivative molecules substituted with inosine plus 2,6-diaminopurine (DAP) . Irrespective of their mode of interaction with DNA, such GC-specific antibiotics as actinomycin, echinomycin, mithramycin and chromomycin find new binding sites associated with DAP-containing sequences and are excluded from former canonical sites containing I.C base pairs . The converse is found to be the case for a group of normally AT-selective ligands which bind in the minor groove of the helix, such as netropsin: their preferred sites become shifted to IC-rich clusters . Thus the binding sites of all these antibiotics strictly follow the placement of the purine 2-amino group, which accordingly must serve as both a positive and negative effector . The footprinting profile of the 'threading' intercalator nogalamycin is potentiated in DAP plus inosine-substituted DNA but otherwise remains much the same as seen with natural DNA . The interaction of echinomycin with sites containing the TpDAP step in doubly substituted DNA appears much stronger than its interaction with CpG-containing sites in natural DNA.

Mol Cell Biochem, 1995 Mar 23, 144(2), 191 - 5
A macrolide antibiotic, roxithromycin, inhibits the growth of human myeloid leukemia HL60 cells by producing multinucleate cells; Nagai M et al.; The antiproliferative effect of roxithromycin (RXM) was studied using human myeloid leukemia HL60 cells . RXM inhibited the growth of HL60 cells in a concentration-dependent manner, and significantly inhibited growth at concentrations above 75 microM . This growth inhibition was not associated with specific cell cycle arrest and DNA synthesis was not impaired . In addition, the number of viable cells remained almost unchanged in the presence of 100 microM RXM . RXM induced growth inhibition at least partly by the formation of multinucleate cells . Both flowcytometric and morphological examination revealed that more than 40% of the RXM-treated cells were binucleate . These findings demonstrate that RXM is a potent new modulator of cell cycle progression in HL60 cells and suggest that the inhibition of cytokinesis by this drug may provide a new model for studying mitosis.

JAMA, 1995 Mar 22-29, 273(12), 957 - 60
Antibiotics in chronic obstructive pulmonary disease exacerbations . A meta-analysis; Saint S et al.; OBJECTIVE--A meta-analysis of randomized trials was performed to estimate the effectiveness of antibiotics in treating exacerbations of chronic obstructive pulmonary disease (COPD) . DATA SOURCES--English-language studies published from 1955 through 1994 were retrieved using MEDLINE, Index Medicus, bibliographies, and consultation with experts . MEDLINE search terms included "COPD," "chronic bronchitis," and "antibiotic(s)." STUDY SELECTION--Only randomized trials that enrolled patients having an exacerbation of COPD, used an antibiotic in the treatment group and placebo in the control group, and provided sufficient data to calculate an effect size were included in the meta-analysis . DATA EXTRACTION--Descriptive and outcome data from each study were independently in the meta-analysis . DATA SYNTHESIS--Overall summary effect size of the nine trials satisfying all inclusion criteria was 0.22 (95% confidence interval {CI}, 0.10 to 0.34), indicating a small benefit in the antibiotic-treated group . Similar analysis of the six studies that provided data on peak expiratory flow rate changes revealed a summary effect size of 0.19 (95% CI, 0.03 to 0.35) and a summary change in peak expiratory flow rate of 10.75 L/min (95% CI, 4.96 to 16.54 L/min) in favor of the antibiotic-treated group . Sensitivity analyses did not significantly affect these results . CONCLUSIONS--These analyses suggest a small but statistically significant improvement due to antibiotic therapy in patients with exacerbations of COPD . This antibiotic-associated improvement may be clinically significant, especially in patients with low baseline flow rates.

FEMS Microbiol Lett, 1995 Mar 15, 127(1-2), 117 - 20
A cytochrome P450-like gene possibly involved in oleandomycin biosynthesis by Streptomyces antibioticus; Rodriguez AM et al.; A cosmid clone from an oleandomycin producer, Streptomyces antibioticus, contains a large open reading frame encoding a type I polyketide synthase subunit and an oleandomycin resistance gene (oleB) . Sequencing of a 1.4-kb DNA fragment adjacent to oleB revealed the existence of an open reading frame (oleP) encoding a protein similar to several cytochrome P450 monooxygenases from different sources, including the products of the eryF and eryK genes from Saccharopolyspora erythraea that participate in erythromycin biosynthesis . The oleP gene was expressed in Escherichia coli as a fusion protein to a maltose-binding protein . Using polyclonal antibodies against this fusion protein it was observed that the synthesis of the cytochrome P450 was in parallel to that of oleandomycin . The cytochrome P450 encoded by the oleP gene could be responsible for the epoxidation of carbon 8 of the oleandomycin lactone ring.

J Biol Chem, 1995 Mar 10, 270(10), 5399 - 404
Purification and characterization of clavaminate synthase from Streptomyces antibioticus . A multifunctional enzyme of clavam biosynthesis; Janc JW et al.; Clavaminate synthase (CS), a key enzyme in the clavulanic acid biosynthetic pathway, has been purified to electrophoretic homogeneity from Streptomyces antibioticus (Tu 1718), a species that does not produce clavulanic acid . A comparison of the physical and kinetic properties of clavaminate synthase from S . antibioticus (CS3) and the two isozymes from Streptomyces clavuligerus (CS1 and CS2) has been conducted . In oxidative reactions requiring the co-substrates O2, alpha-ketoglutaric acid, and catalytic Fe2+, both CS1 and CS2 catalyze three distinct transformations, the hydroxylation of deoxyguanidinoproclavaminic acid to guanidinoproclavaminic acid, and the cyclization and desaturation of proclavaminic acid to clavaminic acid . We have demonstrated that CS3 from S . antibioticus also catalyzes these three oxidations . The apparent molecular mass of CS3 from matrix-assisted laser desorption mass spectrometry is 35,839 +/- 36 Da . The enzyme is a monomer in solution as determined by gel filtration chromatography . Analysis of the four possible proclavaminic acid diastereomers confirmed the absolute configuration of the substrate to be 2S,3R . Based upon N-terminal sequence comparisons among the three proteins, CS3 possesses the higher degree of homology with the CS1 isozyme from S . clavuligerus . Although previously associated solely with clavulanic acid biosynthesis, we propose these findings and recent precursor incorporation data support the view that clavaminate synthase plays a critical role in the biosynthesis of the clavam metabolites.

Biochem Biophys Res Commun, 1995 Mar 8, 208(1), 238 - 44
Induction of apoptosis by enediyne antitumor antibiotic C1027 in HL-60 human promyelocytic leukemia cells; Jiang B et al.; C1027, a new macromolecular antitumor antibiotic with an enediyne chromophore, displays extremely potent cytotoxicity against cancer cells . HL-60 human promyelocytic leukemia cells treated with C1027 (0.1-10 nM) for 2 hours resulted in morphological changes, including Hoechst 33342-stained condensed nuclei, condensation of nuclear chromatin, and nuclear fragmentation . Agarose gel electrophoresis of C1027-treated HL-60 cells showed a typical ladder-like pattern of DNA fragments . In addition, the apoptotic DNA peak of propidium iodide-stained nuclei was revealed by flow cytometry . Treatment of HL-60 cells with C1027 (5 nM) induced apoptosis in up to 79% of the cells . The results suggest that C1027 may exert antitumor activity by triggering apoptosis.

Biochem Biophys Res Commun, 1995 Mar 8, 208(1), 168 - 73
RNA cleavage by C-1027 chromophore, an enediyne antitumor antibiotic: high selectivity to an anticodon arm; Totsuka R et al.; This study demonstrates unique reactivity of the C-1027 chromophore toward a tRNA(phe) . In the presence of Mg2+ ions where the tRNA(phe) attains a stable three-dimensional structure, the enediyne chromophore exhibits high cleavage selectivity to the anticodon arm . The present reactivity of the C-1027 chromophore is useful in development of new chemical probes for mapping of tertiary RNA structure . Considering the paucity of RNA repair mechanisms, RNA may be also an important biological target for certain enediyne antibiotics.

Biochim Biophys Acta, 1995 Mar 8, 1234(1), 43 - 51
The properties of ion channels formed by the coumarin antibiotic, novobiocin, in lipid bilayers; Feigin AM et al.; The coumarin antibiotic novobiocin forms ion channels of varying conductances in lipid bilayers . The conductances (about 20, 22, 14, 7 and 2 pS for 100 mM NH4Cl, CsCl, KCl, NaCl and LiCl, respectively) and selectivities (cation transference numbers in the range of 0.97-0.98) of one type of novobiocin-induced channel are similar to those found for channels formed by gramicidin A, an antibiotic of very different structure . The conductance of novobiocin channels of this type was independent of the species of the membrane lipid . This observation suggests that novobiocin molecules directly form these channels, and that channels are not formed through defects in lipid structure . The similarity in conductance and ion selectivity between channels induced by novobiocin and those formed by gramicidin A suggests that these structurally different molecules form channels with comparable internal diameter and internal surface charge distribution . Using HPLC purification we argue that the channel-forming activity of novobiocin is related to the activity of the novobiocin molecule itself, and not to a contaminant of the commercially available novobiocin sodium salt preparation.

Med J Aust, 1995 Mar 6, 162(5), 249 - 53
Home intravenous antibiotic therapy . A safe and effective alternative to inpatient care; Grayson ML et al.; OBJECTIVE: To assess the practicality, safety, cost effectiveness and outcome of receiving intravenous antibiotics at home . METHODS: Patients with serious bacterial infections requiring parenteral antibiotic therapy were enrolled in a pilot program to receive treatment at home . Antibiotics were premixed in the hospital pharmacy and administered by the Royal District Nursing Service, and medical back-up was provided . RESULTS: Twenty patients (mean age, 58 years; range, 19-84 years) received 21 courses of intravenous antibiotics at home (mean duration +/- SD, 26 +/- 9 days; range, 11-44 days) . Conditions treated included osteomyelitis (10 patients), endocarditis (5), vascular graft and pacemaker sepsis (4), and chronic cellulitis (1) . Treatment at home was well tolerated with no significant complications, and cure was achieved in 18 of the 20 patients . It was both efficient and cost effective, with a mean benefit in treatment costs between home and the equivalent inpatient therapy of at least $112 per day for the 538 days that home therapy was provided . Moreover, the reduced bed use could allow an additional hospital throughput of between 86 and 107 patients annually . CONCLUSIONS: Home intravenous antibiotic therapy is safe, effective and well tolerated . It allows more efficient inpatient care and reduces total treatment costs in an important subpopulation of patients.

J Aerosol Med, 1994 Fall, 7(3), 217 - 28
Assessment of antibiotic aerosol generation using commercial jet nebulizers; Hurley PK et al.; The performance of 14 commercial jet nebulisers has been assessed; Unineb, Suremist (Unimed (UK) Ltd), Micro-Cirrus (Intersurgical Ltd), Pulmo-Neb (DeVilbiss Health Care UK Ltd), Side-Stream (Medic-Aid Ltd), Micro-Neb III (Lifecare Ltd), RespirGard (Marquest Medical Products Inc), Aeromist, Venticaire (S and W Vickers Ltd), Up-Draft II, Ava-Neb, Up-Draft (Hudson Respiratory Care Inc), Bennett/Twin, Raindrop (Puritan-Bennett Corporation) . The units were operated with a high flow compressor (Maxi III, Medix Ltd) at 101/min . Performance was assessed by measuring the fraction of the initial mass of drug released as an aerosol and nebulisation time for initial drug volume of 2-6mls, and the mass median diameter and mass fraction of the aerosol in particles < 5.17 microns diameter . The Side-Stream nebuliser gave the best performance, although incorporation of a filter to trap exhaled antibiotic may prove difficult . The Micro-Cirrus generated a particularly fine aerosol . The Raindrop nebuliser performed well, while the Up-Draft II nebulised efficiently but was associated with extended nebulisation times which may limit its utility.

J Chromatogr A, 1995 Mar 3, 694(1), 195 - 208
Diastereomeric beta-lactam antibiotics . Analytical methods, isomerization and stereoselective pharmacokinetics; Itoh T et al.; Stereospecific HPLC methods for the determination of various diastereomeric beta-lactam antibiotics are reviewed . Stereoselectivity in the absorption, distribution and excretion of several diastereomeric beta-lactams is summarized . The isomerization of beta-lactam isomers and its influence on the pharmacokinetics and pharmacodynamics are discussed.

Eur J Prosthodont Restor Dent, 1995 Mar, 3(3), 111 - 7
The role of antibiotics in the treatment of periodontitis (Part 2--Controlled drug delivery); Needleman IG et al.; Since last reviewing the field, controlled release products have made the jump from research to clinical practice . The potential to extend the efficacy of periodontal therapy with such products is exciting, but also needs careful evaluation . This review will look at recent developments and also will examine the eventual place for these products in periodontics.

Onderstepoort J Vet Res, 1995 Mar, 62(1), 5 - 18
Cardiomyopathy of ruminants induced by the litter of poultry fed on rations containing the ionophore antibiotic, maduramicin . II . Macropathology and histopathology; Bastianello SS et al.; This report contains an account of the gross and histopathological lesions of 20 cattle and four sheep in 15 field outbreaks of poultry litter toxicity, one steer fed ad lib . and six sheep dosed with toxic poultry litter, and ten sheep fed experimental rations containing c 2,5 ppm and 5 ppm maduramicin . The principle macroscopic lesions in most cattle that died in field outbreaks were indicative of congestive heart failure . The lesions in sheep were similar, but generally milder . Cardiac dilatation was observed in both sheep and cattle . Microscopically, the cardiac lesions were more pronounced in cattle and comprised varying degrees of atrophy, hypertrophy, degeneration, necrosis of myocardial fibres, and interstitial fibrosis . Skeletal muscle lesions were usually more severe in sheep, particularly in the muscles of the hindquarters which appeared pale, oedematous and mottled . One of the sheep in the poultry litter dosing trial developed signs of congestive heart failure and the hearts of two others were dilated . Extensive hypertrophy and atrophy of myocardial fibres were evident in the steer fed ad lib . with this material . As in field cases, the myocardial lesions of the sheep were less severe than those of the steer . Mild cardiac dilatation was present in four of the seven sheep in the maduramicin feeding trial . Diffuse hypertrophy of myocardial nuclei was present in all seven cases, myocardial fibre atrophy in six, multifocal fibrosis and necrosis in six and two cases, respectively, and focal endocardial thickening in two . The skeletal muscles revealed granular degeneration and foci of necrosis and regeneration . The cardiac and skeletal lesions in the field outbreaks, poultry litter feeding trials and maduramicin feeding trials, were highly comparable . This suggests that this form of poultry litter intoxication is a chronic form of ionophore toxicity the pathology of which is characterized by a dilated cardiomyopathy with congestive heart failure and mild (cattle) to severe (sheep) skeletal muscle lesions.

J Comput Assist Tomogr, 1995 Mar-Apr, 19(2), 228 - 31
CT of renal densities caused by intravenous infusion of antibiotics; Starinsky R et al.; OBJECTIVE: Patients treated with intravenous antibiotics were seen to have increased attenuation of the renal collecting system on CT scan of the abdomen . To detect whether this was related to certain antibiotics, we undertook a prospective study on patients being treated for sepsis while receiving intravenous antibiotics . In addition, we also tested antibiotics administered to rabbits . MATERIALS AND METHODS: Fourteen patients were tested with cefazolin, gentamicin, cefotaxime, vancomycin, amoxicillin and clavulanic acid (Augmentin), and metronidazole . Ten groups of rabbits received these drugs by intravenous injection . Computed tomography scan of the kidneys was performed prior to and 2 h after intravenous injection of antibiotics . Fourteen patients who underwent CT scan of the abdomen and were treated by intravenous antibiotics were scanned without contrast agent injection . RESULTS: According to our results, cefazolin, cefotaxime, and gentamicin seemed to be the most potent antibiotics in inducing increased attenuation of the collecting system . This effect was synergistic when a combination of drugs was used . CONCLUSION: The elucidation of the potential increase in attenuation of the collecting system by antibiotics in normally functioning kidneys should help to eliminate confusion with other pathologies such as medullary sponge kidney.

Am Surg, 1995 Mar, 61(3), 215 - 9
Meta-analysis of antibiotics in tube thoracostomy; Evans JT et al.; The use of antibiotics for patients undergoing tube thoracostomy was determined to be highly variable based on a study conducted at a national meeting of surgeons . A meta-analysis of six randomized studies previously reported was performed . The analysis was carried out using the Confidence Profile Method software FAST*PRO . The meta-analysis was structured using dichotomous outcomes of infectious chest processes (empyema, effusion, pneumonia, wound infection, tracheitis, etc.) versus no infectious chest process in patients with and without antibiotics . The effect measures calculated included actual difference in probabilities, relative risk, percent differences in probabilities, and odds ratio . The results of this meta-analysis suggest that antibiotics should be used in patients undergoing tube thoracostomy . Antibiotic selection should maximize therapy for Staph . aureus . The implementation of this practice guideline will require the co-operation of multiple specialty oriented physicians and surgeons.

Chest, 1995 Mar, 107(3), 836 - 44
Futility and the common cold . How requests for antibiotics can illuminate care at the end of life; Prendergast TJ; The dominant approach to futility in medicine assumes that the probability and utility of medical interventions may be separated to provide a quantitative (probabilistic) definition of futility . This assumption is not only misleading but also responsible for much of the confusion that futility has engendered in medical discussions . The divorce of utility from probability is the opposite of how clinicians reason: an improbable intervention looks different if it is cheap, easy, and without morbidity than if it is technology intensive, expensive, and likely to involve great pain and suffering . Futility is how physicians describe the sense of being compelled to proceed with resource intensive care for marginal benefits . Outside the intensive care unit, physicians weigh and sometimes reject patient requests without the need to invoke futility . By examining the ways that physicians can legitimately evaluate patient requests, we can show that appeals to futility are both unnecessary and counterproductive . In cases where such appeals are unavoidable, the outpatient model suggests a process to adjudicate the competing claims of patient autonomy and physician responsibility.

Cancer Res, 1995 Mar 1, 55(5), 1075 - 9
In vitro cytotoxicity of a novel antitumor antibiotic, spicamycin derivative, in human lung cancer cell lines; Lee YS et al.; Spicamycin (SPM), produced by Streptomyces alanosinicus, induces potent differentiation in a human leukemia cell line, HL60 . One of the derivatives of SPM (SPM-D), KRN5500, has a wide range of antitumor activity against human cancer cell lines . We examined the cytotoxicity of SPM-D in small and non-small cell lung cancer cell lines using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and colony assays . SPM-D was active against a wide range of lung cancer cell lines . All three cisplatin (CDDP)-resistant cell lines established in our laboratory (PC-9/CDDP, PC-14/CDDP, and H69/CDDP) showed collateral sensitivity to SPM-D with relative resistance values of 0.43, 0.34, and 0.32, respectively . Intracellular SPM-D in PC-14/CDDP was 35% higher than that for PC-14 suggesting that intracellular accumulation can explain the collateral sensitivity to SPM-D at least in PC-14/CDDP . On the other hand, in PC-9/CDDP cells, no increase of intracellular SPM-D accumulation was observed, but the conversion ratio of a metabolite (the amino nucleoside moiety of spicamycin binding with glycine, SAN-G) from SPM-D evaluated by TLC was higher as compared with that of parental PC-9 cells (45.5% versus 37%; PC-9/CDDP versus PC-9) . The increased intracellular metabolism of SPM-D could explain the mechanism of collateral sensitivity in PC-9/CDDP cisplatin-resistant cell lines . To elucidate the determinant of the SPM-D-induced cytotoxicity, we established SPM-D-resistant cell lines, PC-9/SPM-D, PC-14/SPM-D, and H69/SPM-D, by exposing cells to stepwise increases in SPM-D concentration . The relative resistances of these sublines were more than 5000, 46.6, and 37.8 times those of the parental cell lines, respectively . The intracellular concentration of the active metabolite, SAN-G, was found to be decreased in the SPM-D-resistant sublines . This result indicates that the intracellular metabolism of SPM-D to SAN-G is one of the determinants of cellular sensitivity to SPM-D in these SPM-D-resistant cell lines . In conclusion, both drug accumulation and metabolism may contribute to the sensitivity/resistance to SPM-D and both may merit investigation.

Reprod Toxicol, 1995 Mar-Apr, 9(2), 153 - 7
Effect of counseling on maternal reporting of adverse effects in nursing infants exposed to antibiotics through breast milk; Taddio A et al.; In a recent trial, we found that nursing women reported diarrhea in their nursing infants after maternal use of antibiotics . However, because they were told that this could occur during a medication counseling session, the observed effect could have been due to a reporting bias . The objectives of this study were to determine if counseling nursing women about side effects of antibiotic they used could (a) influence the adverse event reporting rate or (b) influence maternal nursing and medication compliance behavior . In a randomized, controlled trial, nursing women calling a teratogen information service for advice about selected antibiotics received one of two possible counseling formats (A and B) . Both groups were informed that the antibiotics were safe to use . Mothers in group B were also informed about a theoretical risk of diarrhea in the infant . Mothers later reported clinical events they noted in the infants and judged whether they were due to the antibiotic . Eighty-seven percent (54/62) of group A subjects compared to 68% (52/76) of group B subjects reported clinical events in their infants during their antibiotic therapy (P = 0.017) . The incidence of reported diarrhea was 26% in group A compared to 17% in group B (P = 0.3); 34% of subjects in both groups attributed clinical events to antibiotic therapy (P = 1.0) . Diarrhea was attributed to antibiotic therapy in 13% of group A and 12% of group B subjects (P = 1.0) . No differences were observed between groups in breastfeeding pattern and antibiotic compliance . Breastfeeding women counseled about adverse effects were not more likely to report side effects in their infants or to change nursing behavior and medication compliance.

Boll Chim Farm, 1995 Mar, 134(3), 156 - 60
{Modification of the pharmacokinetics of some antibiotics by oral administration with an L-(-)verbenone beta-cyclodextrin complex}; Pintabona A et al.; With the aim to evaluate the effect of L (-) Verbenone on the pharmacokinetic of some antibiotics, a compound has been prepared with beta cyclodextrin, allowing the administration per os . Pharmacological studies have been carried out using erythromycin and ampicillin, determining their kinetics in the hepatic and lung tissues after administration to albino mice . The results show that L (-) Verbenone modifies the distribution of the antibiotics used; it increases their concentration at lung level while the concentration at hepatic level remains unchanged.

Antimicrob Agents Chemother, 1995 Mar, 39(3), 781 - 5
Dimerization and membrane anchors in extracellular targeting of vancomycin group antibiotics; Beauregard DA et al.; Antibiotics of the vancomycin group are shown to enhance their affinities for the bacterial cell wall by the devices of either dimerization (vancomycin and other glycopeptides which dimerize even more strongly) or use of a membrane anchor (teicoplanin); a chelate mechanism is suggested in both cases, as supported by antagonism experiments with the cell wall analog di-N-acetyl-L-Lys-D-Ala-D-Ala . These results may have implications for other binding processes which occur near membrane surfaces.

Mol Biol (Mosk), 1995 Mar-Apr, 29(2), 354 - 64
{A synthetic zinc chelating peptide competes for DNA binding sites with antibiotics, adsorbed in a minor DNA groove}; Khokhlov DN et al.; Effects of sibiromicyn, distamicyn A and its analogs on binding to DNA and to poly(dA).poly(dT) are reported for a 23-amino acid synthetic zinc-binding peptide, a part of the DNA-binding domain of the transcriptional activator GAL-4 . Circular dichroism and fluorometry have shown that the synthetic peptide and two distamicyn A analogs compete for binding sites on DNA and on poly(dA).poly(dT) . Antibiotic sibiromycin which forms a covalent bond with a guanine 2-amino group in the minor DNA groove can displace the peptide from a 19 bp self-complementary oligonucleotide serving as a specific target site for Gal-4 protein . The peptide is shown to bind to a glucosylated phage T2 DNA, but its affinity to T2 DNA is weaker than to calf thymus DNA under the same conditions . A method to estimate binding constant and size of the binding site for the synthetic peptide and poly(dA).poly(dT) is proposed based on the binding isotherms of distamycin analogs in the absence and in the presence of the peptide . Using isotherms of binding to poly(dA).poly(dT) for two distamycin analogs with binding constants differing 60-fold, the binding constant of the peptide in the presence of 0.1 M NaCl is estimated as 1.4.10(7)-1.8.10(7) M-1.

Scand J Prim Health Care, 1995 Mar, 13(1), 3 - 7
To prescribe--or not to prescribe--antibiotics . District physicians' habits vary greatly, and are difficult to change; Cars H et al.; OBJECTIVE: To study how different doctors at a primary health care centre prescribe antibiotics for respiratory tract infections, and, if possible, to identify reasons for differences in prescribing habits . DESIGN: All medical visits to the health centre because of respiratory tract infections during January and February were studied in four consecutive years (1990-1993) . The principles for prescribing antibiotics were discussed continuously to obtain more uniform routines . SETTING: The health centre of Teleborg serves a suburban district with about 10,000 inhabitants, and rural surroundings with another 2,000 inhabitants . SUBJECTS: All 2150 visits because of respiratory tract infections (except acute otitis media) made during the studied eight months . All physicians employed at the health centre (five physicians were employed for the whole study period) . MAIN OUTCOME MEASURES: Percentage of visits resulting in prescription of antibiotics, and diagnoses given . RESULTS: Antibiotics were prescribed for 76% of the patients by the most generous doctor, but only for 21% by the most restrictive one . The use of diagnoses suggesting bacterial infection varied in a similar way . Otherwise, the patients of the various doctors looked very much the same, and the return visits for the same complaint during the study months were about 5% for all doctors . In spite of the on-going policy discussions, the doctors kept their positions as generous or restrictive prescribers throughout the study period . CONCLUSION: Doctors have an individual and very constant pattern of prescribing antibiotics, and it seems that the diagnoses are often given to justify the treatment, rather than the other way round.

Chem Pharm Bull (Tokyo), 1995 Mar, 43(3), 378 - 91
Duocarmycins, potent antitumor antibiotics produced by Streptomyces sp . structures and chemistry; Yasuzawa T et al.; Seven novel potent antitumor antibiotics, duocarmycins A (1), C1 (2), C2 (3), D (4), B1 (5), B2 (6) and SA (7), were isolated from three independently collected Streptomyces sp . The complete structures, including absolute stereochemistry, were determined by spectral and chemical studies of those duocarmycins and several derivatives . Duocarmycins A (1) and SA (7) possess a 1,2,7,7a-tetrahydrocycloprop{1,2-c}indol-4-one subunit, a common pharmacophore with that of CC-1065 (10) found from Streptomyces zelensis.

Clin Chest Med, 1995 Mar, 16(1), 173 - 93
Ventilator-associated pneumonia . Failure to respond to antibiotic therapy; Wunderink RG; VAP is clearly associated with an increased mortality, principally because of virulent pathogens such as P . aeruginosa . Part of the increased mortality may be due to inadequacies of antibiotic therapy . Apparent failure of antibiotic therapy has many causes; some are related to deficiencies of the antibiotic therapy, but others are unrelated . Antibiotic failure can be the result of persistence of the original causative organism because of resistance, inadequate local antibiotic levels, anatomic limitations, or to the development of superinfection, either pneumonia or extrapulmonary . Factors probably unrelated to the adequacy of antibiotic regimens include misdiagnosis of the source of infection or causative organism, SIRS associated with the VAP, and the immunocompetency of the host . The pattern of apparent failure can assist in determination of the cause . Four typical patterns are rapid early progression; persistent pneumonia; initial improvement followed by deterioration; and slow, progressive improvement . The deficiencies of tracheal aspirate cultures and portable chest radiographs make determination of the cause of apparent failure difficult by these methods . Therefore, more accurate but invasive or expensive tests are usually required to avoid spiraling empirical antibiotic therapy . Quantitative bronchoscopic cultures and chest CT scans are most likely to lead to an accurate evaluation and appropriate antibiotic changes.

J Antibiot (Tokyo), 1995 Mar, 48(3), 254 - 60
Structure activity studies on chemically modified homologues of the antibiotic phytotoxic leucinostatin A; Vertuani G et al.; The synthesis and a conformational study of a number of homologues of the well known antibiotic, phytotoxic leucinostatin A are reported . The circular dichroism of all the compounds are discussed . Some conclusions on the SAR of these compounds are drawn . The influence of the alpha-helical conformation and/or the increased lipophile character on their interesting biological activities is emphasized.

J Bone Joint Surg Br, 1995 Mar, 77(2), 293 - 5
Epicondylitis after treatment with fluoroquinolone antibiotics; Le Huec JC et al.; We report two cases of epicondylitis of the elbow occurring after treatment with fluoroquinolone antibiotics . Both patients had intense pain which appeared very shortly after the first dose of the drug and was not relieved by conservative treatment . Ultrasonography revealed extensive inflammatory lesions with pseudonecrotic areas . MRI confirmed the lesions and also showed a subclinical abnormality of the adjoining tendons . The persistent nature of the pain was the indication for surgical release of the extensor mechanism . After operation pain disappeared completely and the patients were able to return to their normal activities . Lesions of the tendo Achillis are a well-known side-effect of treatment with fluoroquinolone . Our two cases show that such lesions may occur elsewhere . They also indicate the need for caution when prescribing these antibiotics to patients at risk of tendon lesions, such as top-level sportsmen or patients on dialysis or steroid treatment.

Mol Pharmacol, 1995 Mar, 47(3), 611 - 23
Polymorphism-structure relationships of rifamexil, an antibiotic rifamycin derivative; Bacchi A et al.; The polymorphism of rifamexil, a rifamycin derivative, has been investigated by thermomicroscopy, differential thermal analysis (differential scanning calorimetry-thermogravimetry), IR spectroscopy, and X-ray powder diffraction . Two crystalline forms, an amorphous material, and three solvates have been studied . The crystal structures of two solvates have also been determined by single-crystal X-ray techniques . Although the overall conformation of rifamexil is very similar in the two compounds, marked differences occur between the two crystal packings, due to differences both in the mutual orientation of the molecules and in the rifamexil-solvent interactions . Multivariate statistical methods have been used to identify the principal structural parameters determining the biological activity of the rifamycins.

Nagoya J Med Sci, 1995 Mar, 58(1-2), 41 - 5
Antibiotic and ejaculation treatments improve resolution rate of leukocytospermia in infertile men with prostatitis; Yamamoto M et al.; Leukocytospermia has been associated with notable adverse effects on semen parameters and sperm function . The present study was undertaken to identify men with leukocytospermia and prostatitis in an infertility population and assess the effects of various treatments . One million white blood cells (WBC)/ml semen was defined as leukocytospermia . An expressed prostatic fluid was analyzed for the presence of white blood cells . The presence of more than 10 WBCs/high power field on expressed prostatic secretion was needed for the diagnosis of prostatitis . Those men who had more than one million WBCs in their semen and more than 10 WBCs/high power field on expressed prostatic secretion were enrolled in this study . Of two hundred sixty-three men screened for the presence of leukocytospermia and prostatitis, forty-eight men met both criteria . They were blindly and randomly assigned to one of three groups . Group 1 received no treatment . Group 2 were treated with trimethoprim 80 mg-sulfamethoxazole 400 mg (TMP-SMX) orally twice per day for one month . Group 3 were treated not only with the same antibiotic regimen as group 2 but also were instructed to ejaculate frequently (at least once every three days) for one month . Significant resolution of leukocytospermia occurred in the order of patient groups 3 > 2 > 1 at one month . The resolution rate of leukocytospermia of each group was 76% in group 3, 56% in group 2 and 6.7% in group 1 . The rates in groups 2 and 3 were significantly higher than that in group 1 (p < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

J Infect, 1995 Mar, 30(2), 141 - 6
Systemic amphotericin B versus fluconazole in the management of antibiotic resistant neutropenic fever--preliminary observations from a pilot, exploratory study; Ellis ME et al.; A pilot exploratory study was undertaken to collect preliminary information relating to safety and overall outcome in using intravenous fluconazole (FLUC) for managing antibiotic resistant neutropenic fever (ARNF), with the objective of assessing feasibility of performing a larger prospective controlled study . Patients who were neutropenic from treatment for leukaemia or bone marrow transplantation, received either fluconazole (FLUC) or amphotericin B (AB) . Eight of 16 patients (50%) on FLUC and 21 of 25 patients (84%) on AB defervesced; the mean time to defervescence was 11.0 +/- 10.0 days for FLUC compared to 7.7 +/- 6.3 days for AB, and a similar proportion in each treatment group defervesced within 5 days (50% vs . 52%), respectively . Six of 16 patients (37.5%) on FLUC and three of 25 patients (12%) on AB developed overt invasive fungal disease, including pulmonary aspergillosis (FLUC 4 cases, AB 2 cases) and invasive candidiasis (FLUC 2 cases, AB 0 cases) . The mean time to these events was 19.5 +/- 13.4 (FLUC) and 9.0 +/- 3.6 (AB) days . The fungal related mortality rates were higher in the FLUC group: five of 16 patients (31%) vs . two of 25 patients (18%) died respectively; the time to fungal death was 43.2 +/- 18.2 (FLUC) and 25.0 +/- 18.4 (AB) days . This tendency towards a more favourable outcome in patients on AB may have been due to absence of prior fluconazole prophylaxis in patients subsequently receiving IV FLUC . Analysis of a small subgroup of patients who had all received prior prophylaxis with clotrimazole only, indicated that a greater number of patients subsequently receiving IV FLUC died from fungal disease (5/16 vs.0/6, P = 0.09).(ABSTRACT TRUNCATED AT 250 WORDS)

Pharmacotherapy, 1995 Mar-Apr, 15(2), 201 - 9
National survey of once-daily dosing of aminoglycoside antibiotics; Schumock GT et al.; To evaluate the scope of once-daily dosing of intravenous aminoglycoside antibiotics, a questionnaire was designed and mailed to a random sample of pharmacy directors at 500 acute care hospitals in the United States . The response rate was 68.4% . Nineteen percent of the respondents reported use of once-daily dosing of aminoglycosides . Affiliation with a pharmacy residency program and the presence of a pharmacokinetic consultation service by the pharmacy department were associated with this practice (p < 0.05) . No other statistically significant differences were found . Reported indications, contraindications, and dosing were consistent with those found in the literature . The profession of pharmacy, as demonstrated by pharmacy residency programs and pharmacokinetic consultation services, appears to have been instrumental in implementing this method of dosing aminoglycosides.

J Pharm Biomed Anal, 1995 Mar, 13(3), 219 - 27
Determination of ternary mixtures of antibiotics, by ratio-spectra zero-crossing first- and third-derivative spectrophotometry; Morelli B; The ratio-spectra zero-crossing first- and third-derivative spectrophotometry have been used for determining ternary mixtures of penicillin-G sodium, penicillin-G procain and dihydrostreptomycin sulphate salts . The procedures are accurate, nondestructive and do not require resolutions of equations . In both methods, calibration graphs are linear, with zero-intercept, up to 30 micrograms ml-1 of penicillin-G sodium and penicillin-G procain, and up to 42 micrograms ml-1 of dihydrostreptomycin sulphate . r = 0.9999 in each instance . Working wavelengths, 218.5, 211 and 236 nm, respectively, in the first-derivative mode, and 222.5, 311.5 and 242 nm in the third-derivative mode . Detection limits for each drug at p = 0.01 level of significance were calculated to be 0.058, 0.010 and 0.014 micrograms ml-1 and 0.14, 0.012 and 0.34 micrograms ml-1, in the first- and third-derivative methods, respectively . Both methods apply favorably to either laboratory mixtures or commercial injections.

Klin Oczna, 1995 Mar-Apr, 97(3-4), 66 - 7
{Incidence of hypersensitivity to antibiotics and preservatives in eye drops}; Rudzki E et al.; PURPOSE: To elaborate a set of contact allergens present in eye drops which could precipitate allergic conjunctivitis . Such set has not been yet described in literature . METHODS: Basing on the most frequently used preparations, a set of 15 different substances: drugs and preservatives, was prepared to test the patients . RESULTS: Among the 97 persons who underwent the testing, positive results were observed in 35.5% . The hypersensitivity was found for 11 of the allergens, the most often for neomycin, gentamycin, merthiolate, benzalkonium chloride, and then consecutively for kanamycin, sulfathiazole, oxytetracycline, chloramphenicol, penicillin, boric acid and parabens.

Biochem J, 1995 Feb 15, 306 ( Pt 1), 93 - 100
A novel exocytoplasmic endonuclease from Streptomyces antibioticus; Cal S et al.; A new exocytoplasmic, nutritionally controlled endodeoxyribonuclease (EC 3.1.21.-) was purified to homogeneity from Streptomyces antibioticus . The enzyme showed an apparent molecular mass of 29 kDa (being active in the monomeric form) and a pI of approximately 7.8 . The nuclease hydrolysed endonucleolytically double-stranded circular and linear DNA . The enzyme makes nicks in one strand of the DNA in G-rich regions, leaving either 5' or 3' short, single-stranded overhangs with 3'-hydroxy and 5'-phosphate termini . Breaks in the DNA occur when two nicks in opposite strands are close together . The enzyme had an optimum pH of 7.5 and an absolute requirement for bivalent cations and > or = 100 mM NaCl in the reaction buffer . Activity was greatly diminished in the presence of phosphate, Hg2+ or iodoacetate and was stimulated by dimethyl sulphoxide . Single-stranded DNA was a much poorer substrate than double-stranded DNA . The nuclease hydrolyses sequences of three or preferably more (dG).(dC) tracts in the DNA . The initial specificity shifts to other sequences (including sequences shorter than those initially hydrolysed) during the course of the reaction, giving the changing pattern of bands observed in agarose gels . 5-Methylcytosine-hemimethylated DNA is not hydrolysed by the nuclease . The properties of this novel enzyme suggest a relationship with class II restriction endonucleases and also with some eukaryotic nucleases.

Orv Hetil, 1995 Feb 12, 136(7), 351 - 5
{Comparative study of antibiotic use at hospital departments in 7 Hungarian hospitals 1989-1991}; Almasi I et al.; In their present work, authors, referring to their previous paper, wanted to compare the antibiotic consumption of the special medical fields in different hospitals . Computer database were utilised from different hospitals to obtain the necessary figures concerning antibiotic consumption . The amount of antibiotic consumption was expressed in Defined Daily Dose/1000 hospital day . The great differences found between hospitals in quality of antibiotic consumption related to the same subspeciality can be due to the different therapeutical approach in the respective departments . Quality of drug utilisation did not meet the expectations of the modern antibiotic therapy . Relatively low consumption was found in departments of ophthalmology, neurology, psychiatry and rehabilitation . Medium amount of antibiotic consumption was recorded in departments of internal medicine, general surgery, traumatology, obstetrics and gynecology, E . N . T . and dermatology . High antibiotic consumption was observed at the departments of urology, intensive care, infectology, pediatrics and pulmonology . Authors emphasise the importance of the education of the usage of antibiotics both at the medical universities and in postgraduate training as well.

J Chromatogr A, 1995 Feb 10, 692(1-2), 161 - 6
Liquid chromatographic determination of the macrolide antibiotics roxithromycin and clarithromycin in plasma by automated solid-phase extraction and electrochemical detection; Hedenmo M et al.; A liquid chromatographic method for the determination of the macrolide antibiotics, roxithromycin and clarithromycin, in plasma is described . The method is fully automated, employing on-line solid-phase extraction for sample clean-up, using the Prospekt unit . Plasma samples, mixed with internal standard, were injected onto exchangeable CN cartridges . After washing, the compounds were eluted and transferred to a C18 analytical column for separation and electrochemical detection . Clarithromycin was used as internal standard when assaying roxithromycin and vice versa . The recovery of the solid-phase extraction method was 90% and higher, and the relative standard deviation was about 3% . The limit of quantitation was 0.5 mumol/l when 25 microliters of plasma was injected . Comparison with a liquid-liquid extraction method for sample clean-up showed good agreement.

J Bacteriol, 1995 Feb, 177(3), 818 - 22
Enzymatic synthesis of aminocyclitol moieties of aminoglycoside antibiotics from inositol by Streptomyces spp.: detection of glutamine-aminocyclitol aminotransferase and diaminocyclitol aminotransferase activities in a spectinomycin producer; Walker JB; Extracts of stationary-phase mycelia of the spectinomycin producer Streptomyces flavopersicus ATCC 19756 catalyzed inositol dehydrogenase, L-glutamine:inosose aminotransferase, 2-epi-streptamine:inosose aminotransferase, streptamine:inosose aminotransferase, N3-methyl-2-deoxystreptamine:inosose aminotransferase, and aminodeoxy-scyllo-inositol:inosose aminotransferase reactions, as detected with a new rapid assay procedure . These results suggest that one or both amino groups of the N1,N3-dimethyl-2-epi-streptamine moiety of spectinomycin are derived by transamination from the alpha-amino group of L-glutamine . An enzymatic procedure for distinguishing among N1- and N3-monomethyl diaminocyclitol derivatives and their diaminocyclitol biosynthetic precursors is described . A scheme showing key roles of glutamine-aminocyclitol aminotransferases in biosynthesis of major aminoglycoside antibiotics is presented.

J Urol, 1995 Feb, 153(2), 527 - 9
Antibiotic pharmacokinetics in the inflamed prostate; Nickel JC et al.; We hypothesized that altered pharmacokinetics in the inflamed prostate gland might account for the treatment failure of clinically diagnosed chronic bacterial prostatitis . We employed a rat model of chronic bacterial prostatitis to investigate any pharmacokinetic differences that may exist between uninflamed and inflamed prostate glands . Four groups of animals were studied (treated and untreated control and prostatitis groups) . Seven days of norfloxacin therapy cured 60% of the animals with well-established bacterial prostatitis compared with a spontaneous cure rate of 10% in the nontreated prostatitis animals . Norfloxacin levels did not change significantly between the infected and noninfected prostate glands . We conclude that failure of antibiotic therapy in chronic bacterial prostatitis is not due to significantly altered norfloxacin pharmacokinetics in the chronically inflamed prostate gland but rather to the difficulty of eradicating protected bacterial microcolonies within an infection-induced altered microenvironment deep within the prostate gland.

Aliment Pharmacol Ther, 1995 Feb, 9(1), 47 - 50
Successful Helicobacter pylori eradication incorporating a one-week antibiotic regimen; Hudson N et al.; BACKGROUND: The optimum regimen for the eradication of Helicobacter pylori remains unclear . The aim of this study was to determine the efficacy and tolerability of omeprazole 40 mg daily given for 2 weeks, plus amoxycillin 500 mg t.d.s . and metronidazole 400 mg t.d.s . given for the first 7 days, in the treatment of H . pylori associated peptic ulcer disease . RESULTS: One hundred and thirty-two consecutive patients with peptic ulcer disease were entered into the study (89 male, 41 female; median age 47 years; inter-quartile range: 36-58 years) . H . pylori was eradicated successfully in 109 of 130 patients (intention-to-treat: 83%; 95% confidence limits: 76-89%); per protocol: 85% (95% CI: 78-91%)) . Ninety per cent of patients completed the full course of therapy . Only four patients (3%) stopped treatment as a result of side effects although these occurred in 41% of patients . One patient developed pseudomembranous colitis requiring hospital admission . CONCLUSION: Omeprazole combined with one week of treatment of amoxycillin and metronidazole is an effective and well tolerated Helicobacter eradication regimen . Occasional severe side effects remain a risk, even when the duration of antibiotic exposure is reduced.

Biosci Biotechnol Biochem, 1995 Feb, 59(2), 213 - 8
A close correlation between improvement of organic solvent tolerance levels and alteration of resistance toward low levels of multiple antibiotics in Escherichia coli; Aono R et al.; We have isolated cyclohexane-tolerant mutants from Escherichi coli strain JA300, which is cyclohexane-sensitive and n-hexane-tolerant . These mutants were resistant to low levels of ampicillin, chloramphenicol, nalidixic acid, and tetracycline, and were sensitive to a low level of kanamycin . Spontaneous clones resistant to low levels of the antibiotics, isolated from JA300, showed altered levels of organic solvent tolerance . The clones resistant to ampicillin and chloramphenicol had cyclohexane tolerance . Some of the resistant clones had cyclohexane and n-pentane tolerances . On the other hand, some kanamycin resistant clones became sensitive to n-hexane . Therefore, mechanisms to improve tolerance levels toward organic solvents are closely correlated with some antibiotic resistant system to low levels of antiobiotics.

Indian J Exp Biol, 1995 Feb, 33(2), 97 - 100
Detoxification of a local Microcystis bloom by an algicidal antibiotic from Oscillatoria late-virens; Marwah JB et al.; Mouse toxicity due to microcystin (hepatotoxin) was detected in water bloom of a local lake, comprising mainly Microcystis aeruginosa . Both toxicity and biomass content of the phytoplankton varied seasonally . Incubations with an algicidal metabolite from Oscillatoria late-virens and a herbicide 3-(3,4-dichlorophenyl)-1, 1-dimethyl urea (DCMU) caused depigmentation and detoxification in bloom samples . Algicide-incubation also encouraged growth of protozoa and bacteria, pathogenic form included.

Recenti Prog Med, 1995 Feb, 86(2), 63 - 7
Modification of phlogosis indices in pneumonia during antibiotic therapy; Silvani A et al.; 50 consecutive cases of pneumonia were treated using a standardized diagnostic-therapeutic protocol . The variations of the more common phlogosis indices (erythrocyte sedimentation rate {ESR}, C-reactive protein {CRP}, leucocytes) during the antibiotic therapy were evaluated, together with clinical progress . Comparative evaluations of the phlogosis indices were taken as well as the X-ray picture . The data analysed, according to the literature, showed a significantly faster and more widespread response to the therapy by the CRP, in respect to ESR and the leucocytes number . This data has been substantially confirmed even in individual groups into which the case study was subdivided . In the "compromised" (according to the British Thoracic Society) patients, the fall in the CRP level was not so early as in the "uncompromised" group . There did not seem to be however different behaviour of ESR and leucocytes between these two groups . Modifications in these two tests over time were rarely significant . An age equal to or greater than 70 appears the element which best defines the state of "compromised host" . A comparison of the clinical progress with the variations of the tests of phlogosis and the radiographic tests confirms the usefulness of CRP as an early index of the clinical evolution and the lateness of X-ray tests.

Pharmacol Toxicol, 1995 Feb, 76(2), 128 - 32
Effects of aminoglycoside antibiotics on cholinergic autonomic nervous transmission; Said AA et al.; The effects of eight aminoglycoside antibiotics, gentamicin, neomycin B, ribostamycin, dibekacin B, kanamycin A, streptomycin, tobramycin and amikacin, and two non-aminoglycoside antibiotics, tetracycline and ampicillin, on cholinergic autonomic nervous transmission were studied using isolated guinea-pig ileum preparation . The aminoglycoside antibiotics blocked the transmurally elicited twitches of the ileum in a concentration-dependent manner . The blocking effect of aminoglycosides was biphasic, i.e., an initial reduction followed by a spontaneous partial recovery . Dibekacin was the most potent parasympathetic inhibitor, followed by neomycin B, tetracycline, gentamicin, streptomycin, kanamycin A, tobramycin, ribostamycin, and amikacin . Ampicillin had no blocking effect . The tested antibiotics did not affect acetylcholine (ACh)-induced contraction of the ileum, except for high concentrations of neomycin B, gentamicin, and streptomycin . The three antibiotics shifted the dose-response curves for ACh to the right without affecting the maximal contraction . Naloxon, yohimbine, hexamethonium and choline chloride failed to eliminate the blocking effect of the antibiotics on twitches of the ileum induced by transmural stimulation . However, increase of the extracellular Ca ion concentration virtually abolished the blockade . Dibekacin blocked the evoked but not the spontaneous release of ACh and shifted the dose-response curve of CaCl2-dependent transmurally elicited contractions of the ileum to the right . These results suggest that the site for the block of aminoglycosides is mainly the cholinergic nerve terminal, where they reduce the available Ca ions required for the release of ACh.

Rheum Dis Clin North Am, 1995 Feb, 21(1), 217 - 30
Management of Lyme disease refractory to antibiotic therapy; Sigal LH; Lyme disease has become a major public health problem . One result of this anxiety is over-diagnosis and over-treatment in many endemic and near-to-endemic areas . The diagnosis of Lyme disease is often made solely on the basis of often misinterpreted serologic tests . Therefore, a major reason for inadequate response to antibiotic therapy is initial misdiagnosis . Persisting inflammation and tissue damage following treated Lyme disease does occur but is probably an uncommon cause of refractory symptoms and long-term debility post-Lyme disease.

Eur J Gastroenterol Hepatol, 1995 Feb, 7(2), 117 - 9
Efficacy of omeprazole combined with antibiotics for Helicobacter pylori eradication and duodenal ulcer recurrence; Lazzaroni M et al.; OBJECTIVE: To establish the efficacy of omeprazole combined with two antibiotics for Helicobacter pylori eradication and duodenal ulcer relapse . PATIENTS: Thirty-seven patients with endoscopically proven duodenal ulcer and H . pylori infection . METHODS: Treatment consisted of 20 mg omeprazole daily for 4 weeks with the addition, during the second and third weeks, of amoxycillin (1 g three times daily) and metronidazole (1 g daily) (group A) or placebo (group B) . Endoscopy and biopsy to assess ulcer recurrence and H . pylori status were performed at entry to the study, after 4 weeks of therapy, and 1 and 6 months after treatment . RESULTS: Duodenal ulcers healed in all patients . H . pylori infection was eradicated in 15 (79%) out of 19 patients in group A and one (6%) out of 16 patients in group B (P < 0.01) . One patient in each of the groups was lost to follow-up after 6 weeks . During the 6 month follow-up period, duodenal ulcers recurred in three of the 16 patients with H . pylori eradication, compared with 16 of the 19 patients with persistent H . pylori infection (19 versus 84%; P < 0.01) . CONCLUSION: The combination of omeprazole with amoxycillin and metronidazole is effective in H . pylori eradication . This triple therapy, which eradicates H . pylori, also significantly reduced duodenal ulcer relapse.

Ann Allergy Asthma Immunol, 1995 Feb, 74(2), 167 - 70
Risk of administering cephalosporin antibiotics to patients with histories of penicillin allergy; Anne S et al.; OBJECTIVES: The purpose of this review was to analyze available relevant data regarding the safety of administering cephalosporins to penicillin-allergic patients, including the significance of penicillin skin test reactions and any difference related to first, second, or third generation cephalosporins . BACKGROUND: Penicillin and cephalosporins both contain a beta-lactam ring . This structural similarity has led to considerable confusion about the cross-allergenicity of these drugs and the risks of allergic reactions from cephalosporins in penicillin-allergic patients . METHODS: Published reports and post-marketing data from pharmaceutical corporations provided the basis for this analysis . RESULTS: The overall incidence of adverse reactions from cephalosporins ranges from 1% to 10%, with rare anaphylaxis (< 0.02%) . In patients with histories of penicillin allergy the incidence of cephalosporin reactions is minimally, if at all increased . Post-marketing studies of second and third generation cephalosporins showed no increase in allergic reactions in patients with penicillin allergy histories . Penicillin skin tests do not predict the likelihood of allergic reactions to cephalosporins in patients with histories of penicillin allergy . One reaction occurred in 98 patients (1%) with positive penicillin skin tests and six reactions occurred in 310 patients (2%) with negative tests . CONCLUSIONS: These data indicate that it is safe to administer cephalosporin antibiotics to penicillin-allergic patients and penicillin skin tests do not identify potential reactors.

Antibiot Khimioter, 1995 Feb, 40(2), 3 - 8
{Generation of active forms of oxygen by antibiotics of the tetracycline series during tetracycline catalysis of oxidation of ferrous iron}; Petrenko IU et al.; During oxidation of Fe(2+) catalyzed by tetracyclines there was recorded lucigenin, activated chemiluminescence evident of generation of the oxygen radicals . It was also observed that during the Fe(2+) oxidation by the molecular oxygen catalyzed by tetracyclines there generated hydrogen peroxide which accelerated the Fe(2+) oxidation recorded photometrically by the formation of strongly absorbing tetracycline complexes with Fe(2+) . In the presence of ascorbate reducing Fe(2+) in the complexes with tetracyclines and their subsequent oxidation there generated radicals modifying the antibiotic molecules evident from a change in their absorption spectra after the respective incubation . The results offered a pattern describing the mechanism of the tetracycline toxic effect on biological objects.

Int J Radiat Biol, 1995 Feb, 67(2), 127 - 34
Radiation-induced and free radical-mediated inactivation of ion channels formed by the polyene antibiotic amphotericin B in lipid membranes: effect of radical scavengers and single-channel analysis; Zeidler U et al.; This paper is part of a study on the effect of ionizing radiation on ion channels in biological membranes . Ion channels formed by polyene antibiotics amphotericin B or nystatin represent clusters of conjugated double bonds . As a consequence of this structural peculiarity, the conductance of lipid membranes--in the presence of polyene channels--has been found to decrease by several orders of magnitude at comparatively small doses of ionizing radiation . The phenomenon shows an inverse dose-rate behaviour similar to that of radiation-induced lipid peroxidation . We report on experiments performed in the presence of various radical scavengers, at varying cholesterol concentrations, and with different lipids . They support the view that channel inactivation is due to free radical-induced peroxidation of the polyenes leading to a destabilization of the barrel-like structure of the ion channels . Radiation-induced channel closing is shown for the first time at the level of single-ion channels.

Orv Hetil, 1995 Jan 29, 136(5), 239 - 43
{Comparative study of antibiotic consumption in Hungarian hospitals during 1989-1991}; Almasi I et al.; The data of case histories of the year of 1989 of seven Hungarian hospitals and also the 1990 and 1991 data of two hospitals were collected and integrated in a database . Consumption of antibiotics were represented in DDD (Defined Daily Dose)/1000 hospital day . These data were compared with the data of the drugs delivered by the hospital pharmacy in one of the mentioned hospitals between 1989 and 1992 . It was concluded that data based on case histories represent better the real antibiotic consumption than those of the hospital pharmacy . Reason of this phenomenon is the fact, that considerable amount of drug supply gets out of institutions . Great differences were observed between the seven hospitals in the total amount of antibiotic consumption and between the different antibiotic groups as well . Drugs most frequently used were tetracyclines, broad spectrum penicillins, sulfonamides and aminoglycosides . Consumption of penicillins was decreasing . Regarding new drugs only utilisation of quinolones was increasing . It was concluded, that structure of antibiotic selection did not follow the recommendations of the medical literature . The authors suggest that "antibiotic policy" should be introduced in Hungarian hospitals so as to imporve antibiotic utilisation.

J Chromatogr A, 1995 Jan 13, 689(2), 285 - 304
Highly enantioselective capillary electrophoretic separations with dilute solutions of the macrocyclic antibiotic ristocetin A; Armstrong DW et al.; Ristocetin A is one of a series of structurally related amphoteric, glycopeptide, macrocyclic antibiotics . These compounds have several features that make them attractive as chiral selectors . These include spatially oriented functional groups that are known to provide the types of interactions that are conducive to enantio-recognition, a somewhat rigid "pocket" that can provide a site for hydrophobic interactions and polar, flexible arms (i.e., pendent sugar moieties) that can rotate to hydrogen bond and otherwise interact with a variety of chiral analytes . In addition, these compounds are sufficiently soluble in water, aqueous buffers and aqueous-organic solvents that are commonly used in capillary electrophoresis (CE) . The use and optimization of ristocetin A as a chiral selector in CE is discussed . Over 120 racemates are resolved including a variety of N-blocked amino acids, non-steroidal anti-inflammatory compounds and a large number of biologically important compounds containing carboxylic acid groups (e.g., mandelic acid derivatives, lactic acid derivatives, folinic acid, tropic acid).

FEBS Lett, 1995 Jan 9, 357(3), 235 - 8
Structure of microcin C51, a new antibiotic with a broad spectrum of activity; Metlitskaya AZ et al.; The structure of microcin C51, a new antibiotic produced by E . coli, has been determined . This antibiotic was shown to be a 1.18 kDa nucleotide peptide . It consists of a heptapeptide with formylmethionine as the N-terminus and a C-terminal asparagine linked with nebularin-5'-monophosphate through the three-methylene bridge . The OH-group of threonine is substituted . The peptide chain of microcin C51 synthesized on ribosomes is the longest among the known biologically active nucleotide peptides.

J Basic Clin Physiol Pharmacol, 1995, 6(3-4), 229 - 50
Mechanism of inhibition of protein synthesis by macrolide and lincosamide antibiotics; Menninger JR; During protein synthesis on the ribosome, the growing peptide is linked covalently to a transfer RNA . With a certain probability this peptidyl-tRNA dissociates from the ribosome, whereupon it becomes susceptible to hydrolysis catalyzed by peptidyl-tRNA hydrolase . When placed at nonpermissive temperatures, mutant (pthts) Escherichia coli that are temperature-sensitive for the hydrolase will accumulate peptidyl-tRNA, suffer inhibition of protein synthesis, and eventually die . Treating cells with chloramphenicol before raising the temperature prevents cell death but erythromycin, other macrolides, and lincosamide antibiotics all enhance cell death . Accumulation of peptidyl-tRNA by pthts cells at high temperatures is blocked by chloramphenicol but enhanced by macrolides and lincosamides . The data are most consistent with macrolide and lincosamide antibiotics having as their primary mechanism of inhibition the stimulation of peptidyl-tRNA dissociation from the ribosome . Rather than blocking peptide bond formation or peptidyl-tRNA translocation from the A- to the P-site of the ribosome, these antibiotics allow the synthesis of small peptides which dissociate as peptidyl-tRNAs before being completed . Low doses of erythromycin and lincomycin stimulate preferentially the dissociation of peptidyl-tRNAs that are erroneous . Errors in proteins can be assessed by the time necessary to inactivate beta-galactosidase at > 55 degrees C . Whether erroneous peptidyl-tRNAs are induced by treating E . coli with streptomycin or ethanol, or by starving for an amino acid, the shortened time to inactivate beta-galactosidase is counteracted if the cells are simultaneously treated with erythromycin or lincomycin . In contrast, errors in beta-galactosidase caused by synthesis in the presence of canavanine, an arginine analogue, cannot be counteracted by the simultaneous presence of erythromycin . This result rules out any effect of the drug on post-translational mechanisms of error correction.

Rocz Akad Med Bialymst, 1995, 40(2), 364 - 75
Synthetic analogues of netropsin and distamycin . II . Synthesis of a carbocyclic analogue of the pyrrolecarboxamide antitumour antibiotics; Bartulewicz D et al.; The synthesis of a carbocyclic analogue of netropsin (X) in which N-methylpyrrole rings were replaced by 1,3-disubstituted benzene rings was accomplished in eight steps starting from 4-hydroxyazobenzene-3-carboxylic acid.

Ter Arkh, 1995, 67(10), 31 - 3
{The effect of antibiotics on the body of those working in their manufacture}; Tabakova TV et al.; 541 workers with long-term history of occupational contact with antibiotics and chemicals were examined by a dermatologist, ENT specialist, neuropathologist, surgeon, ophthalmologist . Many workers complained of occasional skin eruption, rhinitis, skin itching, sneezing, cough, Quincke's edema . Allergic examination revealed the presence of allergic symptoms (allergic dermatitis, itch, vasomotor rhinitis, chronic eczema, obstructive bronchitis, bronchial asthma, Quincke's edema, acute and chronic conjunctivitis) in 98 examinees . Somatic affections are represented by hypertension, chronic hepatitis, ulcer.

Scand J Infect Dis, 1995, 27(6), 641 - 2
A case of Brucella melitensis endocarditis successfully treated by a combination of surgical resection and antibiotics; Schvarcz R et al.; Endocarditis is a rare complication of brucellosis, often fatal, and the treatment is controversial . We present a case of Brucella melitensis endocarditis successfully treated by a combination of surgical resection and antibiotics.

Scand J Infect Dis, 1995, 27(6), 603 - 11
Dipslide culture in colonic surgery: a tool for assessment of surgical performance and a guide to antibiotic use; Claesson BE et al.; We evaluated a bacterial culture system for the assessment of surgical performance during colorectal operations, and for assessing the impact of selective postoperative antibiotics in contaminated cases . Surgically related infections were recorded and their risk factors were estimated, using univariate and multivariate methods, in 1079 patients undergoing elective colorectal operations . (Study period 1 was prospective, controlled and randomized, and study period 2 was prospective and open) . All the patients were given metronidazole, 1 g i.v., at induction of anaesthesia and 12 h postoperatively . The number of colony-forming units (CFU) on an intraoperative dipslide culture was classified as 0, 1-4 or > or = 5 (n = 591, 183 and 305) . Patients with > or = 5 CFU were randomized to receive either no further antibiotics or cefuroxime (1.5 g, i.v . every 8 h for 2 days) during the first study period (30 months) . During the second period (84 months), all patients with > or = 5 CFU were to be given cefuroxime . Increasing age (p = 0.014), postoperative transfusion of packed red blood cells (p < 0.001), and high bacterial numbers (p < 0.001) were independently associated with infection . Surgeon-related rates of operative bacterial contamination varied between 12 and 50% (p < 0.001) . In patients given only metronidazole, the likelihood of infection rose as the density of bacteria in the wound increased according to a sigmoid dose-response curve (5.1, 9.8 and 47.5% with CFU 0, 1-4 and > or = 5, respectively) . In the category with > or = 5 CFU, 265 patients were treated with cefuroxime and 23 (8.7%) subsequently had infections {corrected} . Of 40 patients with > or = 5 CFU who did not receive cefuroxime postoperatively, 19 developed infections (p < 0.001, relative risk 5.47; 95% confidence interval 3.29-9.10) . In conclusion, dipslide culture can identify patients at high risk of infection after colonic operations . It can be used to assess surgical performance . The addition of postoperative antibiotic cover for aerobic bacteria, detected by the dipslide, reduced the risk of infection more than 5-fold and almost eliminated the risk of contamination.

Medinfo, 1995, 8 Pt 2, 947 - 51
Adaptation and abstraction as steps towards case-based reasoning in the real medical world: case-based selection strategies for antibiotics therapy; Schmidt R et al.; In this paper we describe an approach to making suitable case-based reasoning methods for real medical world problems . As an example: for the class of therapeutic problems, we choose therapy advice as antibiotics for patients in an intensive care unit, who have an infectious disease as an additional complication . As rapid advice is needed and the agent is unknown, we use an expected agent spectrum based on medical background knowledge and known resistances, which will both be adapted with the results of the laboratory . Case-based reasoning retrieval methods provide the advice for similar former patients . The old solutions are adapted to be applicable to the new medical situation of the current patient . Because of the large and incrementally increasing number of cases, we use prototypes as a structural aid . We present some experimental results of studies about the performance of our prototype design.

Ophthalmic Res, 1995, 27 Suppl 1, 128 - 35
Non-toxic concentrations of cephem antibiotics for intravitreal application--evaluation by in vitro electroretinogram; Kitano K et al.; Non-toxic concentrations of ceftazidime (CAZ), cefuzonam sodium (CZON) and cefmetazole sodium (CMZ) for intravitreal use were assessed by the electroretinogram in in vitro perfused eyecups of albino rabbits . None of the a-wave, the b-wave and the oscillatory potentials deteriorated with 300 microM CAZ, 300 microM CZON or 500 microM CMZ . The oscillatory potentials were delayed and/or diminished at the concentration which did not change the a- and b-waves (500 microM and 1.0 mM for CAZ and CZON, 1.0 mM for CMZ) . Thus, the oscillatory potentials were more vulnerable to these chemicals than the a- and b-waves . Not only the classical a- and b-waves, but also the oscillatory potentials should be examined in retinal toxicology studies by the electroretinogram.

Klin Med (Mosk), 1995, 73(3), 47 - 8
{The antibiotic therapy of patients with hemorrhagic fever with renal syndrome}; Sidel'nikov IuN; Whether preventive antibiotics are beneficial in hemorrhagic fever with renal syndrome was checked up by the evidence obtained from 303 relevant case histories . The analysis showed undesirability of antibiotics, as they promote emergence of nonspecific complications and prolong the patients' stay in hospital.

Proc Annu Symp Comput Appl Med Care . 1995;:651-5.
A decision support tool for antibiotic therapy; Evans RS et al.; We developed a decision support tool to assist physicians anticipating the need for antibiotic therapy . The initial screen alerts physicians of pertinent patient information, provides direct access to other essential medical information, and stimulates clinical judgment by suggesting an antibiotic regimen . The decision support tool also suggests the dose and interval for any ordered antibiotics selected by the physicians . During a 7-month pilot study, all antibiotics for patients admitted to the Shock/Trauma/Respiratory Intensive Care Unit (STRICU) were ordered using the decision support tool . Clinical data from the study period and a 12-month control period (the previous year) were collected and compared . The decision support tool was used to order antibiotics 588 times during the study period and the suggested antibiotics were used 218 (37%) times . The computer suggested dosages were used over 90% of the time . The mean cost of antibiotics was $87.00 (p < 0.04) less per patient during the study period as compared to the control period . Prospective assessment revealed only 3 antibiotic adverse drug events (ADEs) (0.9%) among 336 study patients as compared to 15 ADEs (2.4%) among 626 control patients (p = 0.164).

Acta Microbiol Immunol Hung, 1995, 42(3), 277 - 85
Interaction between tricyclic psychopharmacons and some antibiotics; Molnar J et al.; The tricyclic psychopharmacons, e.g . clozapine, promethazine and imipramine cure plasmids and inhibit plasmid transfer among bacteria due to the inhibition of supercoiling activity on DNA gyrase . In addition an interaction was found between clozapine, imipramine, promethazine and some antibiotics, e.g . penicillins and tetracycline in vitro . The nature of interaction is based on a charge transfer complex, which is formed between clozapine, imipramine, promethazine and penicillins . Differential spectrophotometry showed that ampicillin reduced the highest energy peaks of clozapine, promethazine and imipramine . Streptomycin did not alter the spectrum of clozapine; however, tetracycline somewhat reduced all the peaks of clozapine . Clozapine and promethazine exhibited a synergistic effect with ampicillin, tetracycline and gentamicin on Escherichia coli cells in in vitro . This kind of interaction was missing in the case of imipramine.

J Laryngol Otol, 1995 Jan, 109(1), 24 - 6
The effect of long-term antibiotic therapy upon ciliary beat frequency in chronic rhinosinusitis; Scadding GK et al.; The mucociliary escalator is the first line of defence of the upper and lower respiratory tracts (Greenstone and Cole, 1985; Sleigh et al., 1988) . Failure of mucociliary clearance is associated with chronic or recurrent respiratory tract infection . Ten patients with chronic rhinosinusitis underwent nasal brushings for the assessment of ciliary beat frequency . In two no beating cilia were seen; in the remainder the mean value was 9.3 Hz +/- 2.3; range 6.1-12.8 Hz (n = 8) . Following three months continuous oral antibiotic therapy repeat nasal brushings demonstrated increased ciliary beat frequencies in all patients, mean value 13.7 Hz +/- 1.6; range 11.5-16.3 Hz (n = 10); (p < 0.01; paired t-test) . Depression of mucociliary clearance can occur secondarily to chronic infection and is improved by prolonged antibiotics.

J Antibiot (Tokyo), 1995 Jan, 48(1), 42 - 52
Isolation and structures of an antifungal antibiotic, fusarielin A, and related compounds produced by a Fusarium sp; Kobayashi H et al.; A new antifungal antibiotic, fusarielin A, and three related compounds, fusarielins B, C and D, were obtained from a culture of a Fusarium sp . The skeletal structure and the relative stereochemistry of fusarielin A were determined mainly on the basis of its NMR data, and the absolute structure was elucidated by using the exciton chirality method and the modified Mosher method . The structures of the other homologues were determined by comparison of their spectral data with those of fusarielin A.

Br J Nutr, 1995 Jan, 73(1), 99 - 110
Influence of antibiotics and food intake on liver glutathione and cytochrome P-450 in septic rats; Colomb V et al.; Experimental sepsis in rats induces a restriction in spontaneous food intake and a drop in liver glutathione, cytochrome P-450 (P-450) and aminopyrine demethylase (AD) activity . The present study was designed to assess the effects of antibiotics alone or when combined with food deprivation on these variables . Eighty-nine male Sprague-Dawley rats were assigned to six groups: control (C), acute infection (experimental pyelonephritis, I), acute infection with antibiotics and food given ad lib . (IA), control with antibiotics (CA), acute infection with antibiotics pair-fed to I (IAR), and sham-operated pair-fed to I (SR) . Liver glutathione, P-450 and AD activities were reduced by 45.2, 79.8 and 41.2% respectively in group I . Glutathione and AD significantly increased only in those infected rats given antibiotics and allowed free access to food . P-450 did not normalize within the study period in infected rats receiving antibiotics and food repletion . The risk of drug hepatotoxicity in acute septic states is therefore closely related to the nutritional status . From this point of view, nutritional support is almost as important as treatment of infection.

Leukemia, 1995 Jan, 9(1), 146 - 54
DMSO-like rapid decrease in c-myc and c-myb mRNA levels and induction of differentiation in HL-60 cells by the anthracycline antitumor antibiotic aclarubicin; Stocker U et al.; The anthracycline antitumor antibiotic aclarubicin is known to induce granulocytic differentiation in the human myeloid leukemia cell line HL-60 . We investigated whether this effect is accompanied by changes in the expression of the protooncogenes c-myc and c-myb . Treatment of HL-60 cells with aclarubicin, 50 nM, caused a rapid decrease in c-myc and c-myb mRNA levels within 1 h and 2 h, respectively . In parallel, we demonstrated a strong induction of superoxide-anion production on day 8 of treatment . The kinetics of the effect of aclarubicin on c-myc and c-myb expression were comparable to those associated with the dimethylsulfoxide-induced granulocytic differentiation in this cell line, or to those observed following a chase with actinomycin D, 4 microM . Since aclarubicin partially inhibited total- and poly(A)(+)-RNA synthesis, this macromolecular synthesis inhibition may be causally related to the decrease in c-myc and c-myb mRNA levels . In contrast, the conventional anthracycline doxorubicin, which did not initiate differentiation, failed to affect c-myc or c-myb mRNA levels even in high cytotoxic concentrations, indicating that the suppression of c-myc and c-myb mRNA levels may be an early differentiation-related effect of aclarubicin . On the other hand, actinomycin D, 12.5 nM, and novobiocin, 300 microM, two other known inducers of granulocytic differentiation in HL-60 cells, did not induce an early decrease in c-myb or c-myc expression . Therefore, the immediate suppression of c-myc and c-myb mRNA levels, apparently, is not an obligatory step in chemically induced myeloid differentiation in HL-60 cells, but the common phenomenon in DMSO- and aclarubicin-induced differentiation.

Am Surg, 1995 Jan, 61(1), 11 - 5
Second place winner of the Conrad Jobst Award in the gold medal paper competition . Increased antibiotic effectiveness in a model of surgical infection through continuous infusion; Naziri W et al.; As long as infection remains the most common cause of morbidity and mortality in severely ill patients, there exists the need for more effective anti-infective therapy . The current study was undertaken to determine whether continuous infusion (CONT) is superior to intermittent administration (INT) of an equal amount of cefazolin (CEF) in a model of surgical infection . The thigh suture model consists of the surgical placement of 1 cm of cotton suture with absorbed K . pneumoniae into the thigh muscle of mice . The experimental groups were: 1) controls (n = 20) with thigh suture inoculation and treatment with intraperitoneal (IP) sterile saline; 2) CONT infusion group that received CEF at 60 mg/kg IP 30 minutes before inoculation followed by CONT IP infusion at 180 mg/kg/day (n = 22) for 3 days; and 3) INT injection group that received CEF at 60 mg/kg IP 30 minutes before inoculation followed by INT IP injections every 8 hours at 180 mg/kg/day (n = 20) for 3 days . All CEF treated animals received identical quantities of total CEF, and all groups were followed for 10 days . The control and INT CEF groups had 20% survival, whereas the CONT CEF group had 81% survival, (P < 0.001) . Continuous CEF yielded constant serum levels of 19 +/- 1 micrograms/mL, whereas INT injections resulted in peak serum level of 74 +/- 12 micrograms/mL at one minute but declined to 3.9 +/- 0.9 micrograms/mL in 2 hours . Although there was statistically significant tissue bacterial growth in the INT injection group, there was extensive tissue bacterial clearance in the CONT infusion group.(ABSTRACT TRUNCATED AT 250 WORDS)

Fertil Steril, 1995 Jan, 63(1), 142 - 7
Antibiotic therapy and leukocytospermia: a prospective, randomized, controlled study; Yanushpolsky EH et al.; OBJECTIVE: To determine the efficacy of common antibiotic therapies for treatment of leukocytospermia of unknown etiology . DESIGN: Prospective, randomized, controlled clinical study . SETTING: Fertility and Endocrinology Unit at Brigham and Women's Hospital, Boston, Massachusetts . PATIENTS: One thousand seven hundred ten male partners in infertile couples attending the Fertility and Endocrinology Unit . INTERVENTIONS: Concentrations of seminal peroxidase-positive granulocytes were determined during all routine semen analyses performed over a 30-month period . Of 119 men found to have leukocytospermia (> 10(6) granulocytes/mL semen) on first visit, 54 agreed to be randomized into one of three groups, and 41 patients completed the study . Group I (n = 13) and their wives received a 14-day course of oral doxycycline, 100 mg twice per day . Group II (n = 11) and their wives received a 14-day course of oral trimethoprim 160 mg-sulfamethoxazole 800 mg twice per day . Group III (n = 17) and their wives received no therapy . Four weeks after randomization, repeat semen analyses and granulocyte quantitations were done . RESULTS: Neither of the antibiotic regimens resulted in a significantly higher rate of resolution of leukocytospermia over that seen in the control group . CONCLUSIONS: There is a high rate of spontaneous resolution of leukocytospermia after one positive test . Antibiotics are no more beneficial than no therapy for treatment of this condition.

Respiration, 1995, 62 Suppl 1, 19 - 24
Aerosol administration of antibiotics; Smith AL et al.; Aerosol administration of antibiotics is an attractive approach to the treatment of the recurrent respiratory infections experienced by patients suffering from cystic fibrosis (CF) . Through aerosol administration, drugs can, theoretically, be delivered directly to the target site of infection, i.e . the lumen of the lower respiratory tract, thus enabling smaller doses to be given . This, in turn, should result in reduced costs and decreased potential for systemic toxicity . The efficacy of aerosol antibiotic therapy is, however, influenced by numerous variables, including the type of nebulizer device used to deliver the aerosol, the drug's physical properties, its concentration in the aerosol and particle size, carrier gas and patient factors . The efficacy of aerosol antibiotics in the treatment of CF is controversial . This appears to be due mainly of problems and inconsistencies with clinical trials . However, various antibiotics, including beta-lactams, polymyxins and aminoglycosides, have demonstrated clinical benefits when administered by inhalation to CF patients.

Cancer Chemother Pharmacol, 1995, 36(2), 149 - 54
Antibiotic C3368-A, a fungus-derived nucleoside transport inhibitor, potentiates the activity of antitumor drugs; Su J et al.; Antibiotic C3368-A (CA) is produced by a fungus strain from a soil sample collected in Antarctica . CA markedly inhibited radiolabeled thymidine and uridine transport in mouse Ehrlich carcinoma cells, its 50% inhibitory concentration (IC50) being 4.6 and 7.7 microM, respectively . In clonogenic assay, CA displayed a synergistic effect with methotrexate (MTX), mitomycin C (MMC), 5-fluorouracil (5FU), and Adriamycin (ADR) against human oral epidermoid carcinoma KB cells . CA also markedly enhanced the inhibitory effect of 5FU and ADR on the proliferation of human hepatoma BEL-7402 cells as determined by the p-nitrophenyl-N-acetyl-beta-D-glucosaminide (NAG) enzyme-reaction assay . 5FU or ADR cytotoxicity was not augmented by CA in human fetal lung 2BS cells . In vivo, CA significantly potentiated the inhibitory effect of MMC against colon carcinoma 26 in mice . No significant augmentation of toxicity by the combination was found in treated mice . The results suggest that CA, the newly found nucleoside-transport inhibitor, may be useful in potentiation of the effect of antitumor drugs.

Langenbecks Arch Chir, 1995, 380(2), 102 - 7
{Ulcus cruris venosum: surgical debridement, antibiotic therapy and stimulation with thrombocytic growth factors}; Coerper S et al.; Despite the availability of various topical agents and of new technics for surgical correction, venous stasis ulcers are still characterized by high recurrent rates . Experimental data from wound healing studies demonstrate stimulation of wound healing after topical application of various growth factors (TGF beta, PDGF, EGF) . The results of clinical studies suggest that topical use of an autologous platelet releasate (PDWHF) containing various growth factors accelerates healing . In this prospective study the stimulating effect of autologous PDWHF on epithelialization of small ulcers (group A, < 5000 mm2) and granulation of large ulcers before mesh grafting (> 5000 mm2) will be demonstrated . Inclusion criteria were the venous aetiology of the ulcer and the failure of conventional therapy for 6 month . Exclusion criteria were arterial occlusive disease, diabetes mellitus, acute wound infection, thrombocytopenia and pregnancy . There were 24 patients with 36 ulcers, caused by postthrombotic syndrome in one-third of cases and in two-thirds by severe insufficiency of the perforating veins . The ulcer had been present for more than in 10 years in 38% of cases, while there were 6 circumferential ulcers . The overall ulcer healing rate was 77% after a mean of 14 weeks . In group A 78% of the patients were healed after a mean of 16 weeks . In group B the mesh graft procedure was successful in 90% of the patients after a mean of 13 weeks . Compared with other conventional therapy studies, we achieved a higher healing rate . PDWHF seems to create ideal granulation tissue for mesh graft, indicated by a high uptake of the skin grafts.(ABSTRACT TRUNCATED AT 250 WORDS)

Trans R Soc Trop Med Hyg, 1995 Jan-Feb, 89(1), 107 - 10
Antibiotic regimen as an independent risk factor for disseminated fungal infections in neutropenic patients in Brazil; Nucci M et al.; In a cohort of 79 febrile episodes in 50 consecutive neutropenic patients seen at the University Hospital, Federal University of Rio de Janeiro, Brazil, between 1987 and 1991, it was observed that the cumulative incidence of disseminated fungal infections rose from 3% to 19% after the introduction of a new empirical antibiotic regimen . In order to identify risk factors, as well as to assess the impact of the new antibiotic regimen on the emergence of fungal infections, a nested case-control study was undertaken, in which 10 cases of disseminated fungal infections were compared with 30 randomly chosen controls, drawn from the same cohort . In a multiple logistic regression analysis, the predictive factors for disseminated fungal infection were younger age (odds ratio 0.85, 95% confidence interval 0.75-0.97) and use of the new antibiotic regimen (odds ratio 14.18, 95% confidence interval 1.05-191.80) The probable explanation for the emergence of fungal infections is that the new antibiotic regimen, by lowering the incidence of bacteraemia-related deaths, allowed patients to be at risk for the development of disseminated fungal infections.

Comput Methods Programs Biomed, 1995 Jan, 46(1), 13 - 21
The antibiotic cost calculator; an expert system for global antibiotic cost calculation; Kerr J; An application to cost antibiotic therapy was developed using Object Vision, an object-oriented software development program . The application facilitates calculation of the cost of up to six antibiotics (three oral and three intravenous) in terms of acquisition, delivery, laboratory and complication components . The application consists of two files . The first file allows entry of basic cost data . The second file allows the user to define each antibiotic regimen and the management, and thus the cost, of complications relevant to the antibiotics being costed; costs are automatically calculated and displayed . The program also contains a help system; this comprises extensive explanation of each stage of the calculation process, a summary of recent literature on the percentage incidence of complications for commonly used antibiotics, and a bibliography . The summary and bibliography may be printed . The program is designed for use by hospitals, universities and pharmaceutical companies for calculation of total in-patient charges, marketing and research . It is a user-friendly system which dramatically reduces the inherent complexities of this area of medicine.

Acta Otorrinolaringol Esp, 1995 Jan-Feb, 46(1), 41 - 4
{Prophylactic antibiotic therapy with amoxicillin-clavulanic acid in oropharyngeal surgery}; Navarro M et al.; The present paper shows the results of a randomized, prospective trial carried out on 170 patients undergoing elective surgery for oropharyngeal cancer . These patients were distributed in two groups that received a prophylactic therapy with amoxicillin and clavulanic acid, for 24 hours and 5 days, respectively . Comparing results of short-term and long-term prophylaxis . Among patients undergoing only total or partial laryngectomies, no differences between both groups were found . Among patients who already had a tracheostomy, the rate of local infection was higher in the short-time group . Duration of prophylaxis in high-risk surgery, such as that requiring flap reconstruction, needs further investigation.

Vasa, 1995, 24(1), 19 - 22
Influx of antibiotics into diabetic legs with plantar ulcerations: regional and systemic Netilmycin levels compared after retrograde-venous and systemic-venous application; Seidel C et al.; Retrograde venous perfusions (RVP) of antibiotics were proven to be therapeutically more effective than systemic venous infusions (SVI) in patients with infected diabetic neuropathic plantar ulcers (DNPU: no additional macronagiopathy of leg arteries) . In order to study some pharmakokinetic features of RVP application paratibial tissue levels of Netilmycin (NL; from suction blister fluid) and cubital venous NL were compared under each SVI and RVP therapy in 8 patients with DNPU . Tissue (11.6 +/- 6.4 micrograms/l) were significantly higher (p < 0.001) an within the therapeutic range after RVP (SVI: 4.31 +/- 1.68) . In ulcer transsudate (RVP only; n = 4) NL mounted to 36.4 +/- 11.6 microgram/ml . Peak and base NL in cubital blood were within the normal range for both SVI and RVP (no significant difference) . The date indicate that RVP is superior to SVI application of Netilmycin (and probably other antibiotics) as surmounting the damaged microcirculation in DNPU to achieve effective drug levels in the target tissue.

Artif Cells Blood Substit Immobil Biotechnol, 1995, 23(1), 81 - 8
In vitro drug release of antibiotic-loaded porous hydroxyapatite cement; Tung IC; A model was proposed for describing the observed in vitro release behavior of drugs from porous HAPs . The model consists of three successive stages; during the first stage, the dissolution medium penetrating into the porous HAP, the amount of the drug released is proportional to the square root of release time . During the second stage, after the pores in the HAP are filled out by the dissolution medium, the drug release being proceeded by dissolution into the dissolution medium outside of the HAP, the amount of the drug released is proportional to release time . During the third stage, after the drug concentration is decreased and below the solubility limit of the drug in the dissolution medium, the drug diffusing to the stirred dissolution medium outside of the HAP, the release rate is markedly slowed and the release amount approaches a plateau value.

Int J Clin Pharmacol Ther, 1995 Jan, 33(1), 32 - 3
Investigation on antibiotics in a hospital for a one-year period; Atanasova I et al.; Defined daily dose (DDD) units were used to analyze the antibiotic utilization in a University Military Hospital for a one-year period . The data were collected from hospital records . The mostly prescribed drug groups were penicillins (broad-spectrum), systemic sulfonamides and combinations and tetracyclines . Amoxycillin, doxycycline and co-trimoxazole were most frequently used . Circannual variations were observed only in the utilization of amoxycillin and doxycycline during the year.

Lab Anim, 1995 Jan, 29(1), 45 - 9
Multifactorial analysis of antibiotic sensitivity of Bordetella bronchiseptica isolates from guineapigs, rabbits and rats; Boot R et al.; The possible relationship between antibiotic sensitivity of B . bronchiseptica isolates and host species was examined . Growth inhibition of 11 B . bronchiseptica isolates from guineapigs, 7 from rabbits and 3 from rats by a variety of antibiotics incorporated in paper disks, was tested . To seek possible relationships among the various antibiotic sensitivities, we submitted our datamatrix to principal component analysis and subsequently to cluster analysis . This approach showed the existence of close clustering as well as highly specific antibiotic sensitivities . In order to test the presumed relationship between antibiotic sensitivity profiles of the B . bronchiseptica isolates and host species of origin, the same datamatrix was submitted to discriminant analysis . Antibiotic sensitivity profiles of the isolates were not clearly related to host species.

J AOAC Int, 1995 Jan-Feb, 78(1), 49 - 54
Liquid chromatographic determination of beta-lactam antibiotics in milk: a multiresidue approach; Moats WA et al.; In the United States, testing of all milk for residues of beta-lactam antibiotics is now mandatory . Although a number of screening tests for determination of beta-lactam antibiotic residues have been proposed, few reference methods of the required sensitivity (< 10 ppb) are available . Methods for determination of several beta-lactam antibiotics using an automated liquid chromatography (LC) cleanup have been described recently . This paper describes the integration of these methods into a single extraction and cleanup procedure . Milk was deproteinized with 0.2M Et4NCI and acetonitrile . The resulting filtrate was evaporated to about 1 mL, made to 4 mL, and filtered through a disposable filter cartridge . For cleanup, 2 mL filtrate was loaded onto a bonded C18 LC column in 0.01M KH2PO4 (A) and eluted with an acetonitrile (B) gradient using a program of 100 A:0 B(0-3 min) to 60 A:40 B (30 min) . The beta-lactams were concentrated into narrow bands and separated from each other . A fraction corresponding to each compound of interest was collected and rechromatographed for analysis . The procedure has been applied successfully to determination of ampicillin, amoxicillin, cephapirin, penicillin G, penicillin V, ceftiofur, and cloxacillin . In principle it can be applied to the determination of any beta-lactam antibiotic or metabolite thereof by collecting the appropriate fractions.

J Am Board Fam Pract, 1995 Jan-Feb, 8(1), 7 - 16
Cost-effectiveness analysis of five different antibiotic regimens for the treatment of uncomplicated Chlamydia trachomatis cervicitis; Nuovo J et al.; BACKGROUND: The new Centers for Disease Control and Prevention treatment guidelines for Chlamydia trachomatis include two recently available drugs, azithromycin and ofloxacin . The best choice for initial therapy remains controversial . OBJECTIVES: We wanted to perform a cost-effectiveness analysis of five different antibiotic regimens for the treatment of uncomplicated Chlamydia trachomatis cervicitis . METHODS: Using information gathered from a MEDLINE search of the English language literature from 1966 to 1994, employing the key words "cervicitis," "C . trachomatis," "erythromycin," "tetracycline," "doxycycline," "ofloxacin," and "azithromycin," we developed a decision analysis model specific for a nonpregnant woman with uncomplicated Chlamydia trachomatis cervicitis . Options in this model included an initially cured infection, a failed initial cure resulting in persistent cervicitis, or pelvic inflammatory disease treated either on an inpatient or outpatient basis . Probability estimates for each option were derived from previously published reports . A cost-effectiveness analysis was performed for three end points: cost per cure with initial therapy, cost per case of pelvic inflammatory disease averted, and cost per hospitalization averted . Sensitivity analyses were done by varying the cure rates for each antibiotic and the complication rates for failed therapy . The costs incurred for treatment were also varied . RESULTS: Using the high estimate for initial cure rates, doxycycline and tetracycline were the most cost-effective agents . Azithromycin was the next most cost-effective agent, followed by ofloxacin and erythromycin . To achieve an equivalent final cost, the probability of initial cure with azithromycin must exceed that of doxycycline by 3 percentage points . As the cost of azithromycin decreases, the difference in initial cure rates between the two drugs to achieve an equivalent final cost becomes smaller . CONCLUSIONS: Doxycycline remains the drug of choice in the treatment of Chlamydia trachomatis cervicitis . The results favor the use of azithromycin rather than doxycycline when there is concern for compliance to the standard doxycycline regimen . A lower cost for azithromycin could favor its use as the drug of choice.

Nihon Kyobu Shikkan Gakkai Zasshi, 1995 Jan, 33(1), 51 - 6
{Treatment of aspiration pneumonia with low-dose methylprednisolone and antibiotics}; Hatakeyama S et al.; Low-dose methylprednisolone and antibiotics were used to treat 30 patients with aspiration pneumonia, in a prospective, randomized, double-blind trial with placebo control . All patients received clindamycin phosphate 1200 mg per day . In addition, 15 patients received methylprednisolone 20 mg per day for three days and the other 15 patients received placebo according to the same schedule . In the methyl prednisolone group, CRP had decreased (p < 0.05) from 12.7 +/- 9.8 to 6.4 +/- 5.4 mg/dl day 4, neutrophil elastase had decreased (p < 0.05) from 402 +/- 304 to 231 +/- 64 micrograms/dl by day 4 and to 184 +/- 59 micrograms/dl by day 7, maximum body temperature had decreased (p < 0.01) from 37.9 +/- 1.1 to 36.8 +/- 0.6 degrees C by day 7, and the pneumonia score had improved (p < 0.01) from 11.8 +/- 3.0 to 8.6 +/- 2.4 by day 4 . In the placebo group, there were no significant improvements by those days . We conclude that low-dose methylprednisolone therapy with antibiotics is effective against aspiration pneumonia.

Antimicrob Agents Chemother, 1995 Jan, 39(1), 45 - 9
Effects of two antibiotic regimens on course and persistence of experimental Chlamydia pneumoniae TWAR pneumonitis; Malinverni R et al.; We studied the effects of two antibiotic regimens on the course of Chlamydia pneumoniae infection in the lungs of Swiss Webster mice . After intranasal challenge with isolates AR-388 (1.3 x 10(7) inclusion-forming units per mouse) and AR-39 (1.5 x 10(6) inclusion-forming units per mouse), groups of animals were treated with either doxycycline (10 mg/kg of body weight once a day for 3 days), azithromycin (10 mg/kg {single dose}), or saline . Responses were assessed by the isolation of organisms in cell culture, detection of TWAR DNA in lung tissues by PCR, and lung histology . Both regimens were effective in clearing infections induced by AR-388 (P = 0.02 and 0.007 for doxycycline and azithromycin, respectively) compared with controls . TWAR DNA was detected in 77 and 25% of culture-negative lungs 2 weeks after treatment of AR-388 and AR-39 infections, respectively . Histological changes showed interstitial pneumonitis and were similar over time for all groups . Single-dose azithromycin produced drug levels in lung tissues above the MICs for the test strains for a period three times longer than that of single-dose doxycycline . We concluded that short-term antibiotic regimens were successful for the treatment of experimental TWAR pneumonitis in mice . TWAR DNA was frequently recovered from lung tissues after apparently successful treatment.

Antimicrob Agents Chemother, 1995 Jan, 39(1), 245 - 6
High efficacy of short-term quinine-antibiotic combinations for treating adult malaria patients in an area in which malaria is hyperendemic; Metzger W et al.; In a randomized trial, a three-dose quinine monotherapy was compared with short-term combination regimens of quinine-clindamycin and quinine-doxycycline for treating adult Gabonese patients with Plasmodium falciparum malaria . In quinine-treated patients, only 38% were ultimately cured . In contrast, more than 90% of patients were cured after treatment with either combination regimen.

Antimicrob Agents Chemother, 1995 Jan, 39(1), 232 - 7
Relationship between structure and convulsant properties of some beta-lactam antibiotics following intracerebroventricular microinjection in rats; De Sarro A et al.; The epileptogenic activities of several beta-lactam antibiotics were compared following their intracerebroventricular administration in rats . Different convulsant potencies were observed among the various beta-lactam antibiotics tested, but the epileptogenic patterns were similar . The patterns consisted of an initial phase characterized by wet-dog shakes followed by head tremor, nodding, and clonic convulsions . After the largest doses of beta-lactam antibiotics injected, clonus of all four limbs and/or the trunk, rearing, jumping, falling down, escape response, transient tonic-clonic seizures, and sometimes generalized seizures were observed, followed by a postictal period with a fatal outcome . At a dose of 0.033 mumol per rat, cefazolin was the most powerful epileptogenic compound among the drugs tested . It was approximately three times more potent than benzylpenicillin in generating a response and much more potent than other cephalosporins, such as ceftriaxone, cefoperazone, and cefamandole . No epileptogenic signs were observed with equimolar doses of cefotaxime, cefonicid, cefixime, and ceftizoxime in this model . The more convulsant compounds (i.e., cefazolin and ceftezole) are both characterized by the presence of a tetrazole nucleus at position 7 and show a marked chemical similarity to pentylenetetrazole . Imipenem and meropenem, the two carbapenems tested, also showed epileptogenic properties, but imipenem was more potent than meropenem, with a convulsant potency similar to those of ceftezole and benzylpenicillin . In addition, the monobactam aztreonam possessed convulsant properties more potent than those of cefoperazone and cefamandole . This suggest that the beta-lactam ring is a possible determinant of production of epileptogenic activity, with likely contributory factors in the substitutions at the 7-aminocephalosporanic or 6-aminopenicillanic acid that may increase or reduce the epileptogenic properties of the beta-lactam antibiotics . While the structure-activity relationship was also investigated, there seem to be no convincing correlations among the rank order of lipophilicities and the convulsant potencies of the compounds studied . The lack of marked convulsant properties of cefixime, cefonicid, cefuroxime, and cephradine suggests that these antibiotics may interact with a binding site which is different from that by which the beta-lactam antibiotics exert their convulsant effects or may demonstrate a reduced affinity for the relevant site(s).

Rapid Commun Mass Spectrom, 1995, 9(10), 883 - 7
Investigation of complexes between some glycopeptide antibiotics and bacterial cell-wall analogues by electrospray- and capillary zone electrophoresis/electrospray-mass spectrometry; Hamdan M et al.; Complexation in aqueous solutions between vancomycin, ristocetin A, teicoplanin and two bacterial cell-wall analogues, Ac2-L-Lys-D-Ala-D-Ala (tripeptide) and Ac-D-Ala-D-Ala (dipeptide) has been examined by positive-ion electrospray mass spectrometry (ES-MS) and capillary zone electrophoresis (CZE)/ES-MS . The ES-MS data demonstrate that as well as complexes between monomeric antibiotics and either peptide, the investigated solutions contained complexes ranging from the simple homodimer of the antibiotic to a more complex association giving ions of the type {2(antibiotic) + 3(tripeptide) + 3H}3+ . The same data also demonstrate that the homodimers of the investigated antibiotics are significantly suppressed in the presence of the tripeptide . The use of CZE/ES-MS made it evident that the complexes between the antibiotic and the tripeptide were present in the solution prior to their introduction into the ion source . The two sets of data are compared with existing UV difference spectroscopy and nuclear magnetic resonance data on complexation and dimerization.

Int J Clin Lab Res, 1995, 25(2), 93 - 8
Antibiotic effects on phagocyte chemiluminescence in vitro; Pierce LA et al.; Phagocytes are an essential defence against infection . Since drugs which affect their function may alter the outcome of infections, we have studied the effect of nine antibiotics on phagocyte function in vitro . The effects of antibiotics on the respiratory burst function of phagocytes from healthy adult donors were investigated using lucigenin-enhanced chemiluminescence in response to serum-opsonised zymosan . Aminoglycosides showed dose-dependent suppression of polymorphonuclear leucocyte chemiluminescence, except streptomycin which caused enhancement . Erythromycin caused profound suppression of chemiluminescence from both polymorphonuclear leucocytes and monocytes . Benzylpenicillin and the cephalosporins caused variable suppression of phagocyte chemiluminescence: cefotaxime increased monocyte chemiluminescence in some experiments . None of the drugs produced suppression at clinically relevant plasma concentrations, but erythromycin and some other drugs are preferentially concentrated in phagocytes to levels which suppress their oxidative metabolism in vitro . It is therefore possible that some antibiotics alter phagocyte function: ex vivo studies of phagocyte function in patients taking antibiotics would be valuable.

Yao Xue Xue Bao, 1995, 30(5), 336 - 42
{Relationship between the molecular composition of C1027, a new macromolecular antibiotic with enediyne chromophore, and its antitumor activity}; Shao RG et al.; The molecule of C1027, an antitumor antibiotic with extremely potent cytotoxicity against cultured cancer cells, is composed of an enediyne chromophore and an apoprotein of 10.5 kDa . These two parts of the molecule, connecting each other through non-covalent binding, can be dissociated and reconstituted . As determined by clonogenic assay, the chromophore served as the active part of the molecule, displaying potent cytotoxicity similar to that of intact C1027 . The activity of free chromophore decreased more rapidly than that of intact C1027, indicating that apoprotein played a role in protecting the chromophore from inactivation . By incubating together in phosphate buffer, the chromophore and apoprotein were reconstituted to form an intact C1027 . The ratio of chromophore and apoprotein remained 1 : 1 in the reconstituted molecule, even though extra amount of chromophore was added . The optimal condition for the reconstitution was pH 7.0, at 20 degrees C for 12 h . When the disulfide bond of the apoprotein was reduced by DTT, the activity of C1027 decreased more rapidly . C1027 was digested by pronase and the produced fragments of various molecular weights were examined by capillary electrophoresis . The cytotoxicity of 3-5 kDa fragment approximated that of intact C1027 and its IC50 value was 0.07 fmol.L-1 . The results indicate that the intactness of the apoprotein is not indispensable for stabilizing the chromophore and a smaller molecule of 3-5 kDa consisting of a peptide fragment and a chromophore may retain full C1027 activity.

Rapid Commun Mass Spectrom, 1995, 9(8), 707 - 11
Structural characterization of a new class of penem beta-lactam antibiotics by triple quadrupole tandem mass spectrometry; Triolo A et al.; A series of new penem beta-lactam antibiotics, having at position 2 of the thiazoline ring an amido-substituted amino acid moiety spaced by a methylene group, was analyzed by collisionally activated dissociation (CAD) tandem mass spectrometry on a triple-quadrupole mass spectrometer, after ionization by cesium ion bombardment . This approach allowed complete structural characterization without any matrix interferences . All the compounds investigated underwent beta-lactam ring cleavage through a typical retro-Diels-Alder reaction, as well as cleavage of the 2-side chain at two different points, with charge retention on both sides of the molecule . Subsequent fragmentation reactions essentially involved combinations of the above processes.

Acad Emerg Med, 1995 Jan, 2(1), 4 - 10
Prospective evaluation of topical antibiotics for preventing infections in uncomplicated soft-tissue wounds repaired in the ED; Dire DJ et al.; OBJECTIVE: To determine differences in infection rates among uncomplicated, repaired wounds managed with: topical bacitracin zinc (BAC); neomycin sulfate, bacitracin zinc, and polymyxin B sulfate combination (NEO); silver sulfadiazine (SIL); and petrolatum (PTR) . METHODS: This was a prospective, randomized, double-blind, placebo-controlled study conducted at a military community hospital with an emergency medicine residency program . Patients were enrolled if they: presented to the ED within 12 hours of injury and did not have puncture wounds, allergies to the agents used, or a history of immunocompromise; were not receiving antibiotics, chemotherapy, or steroids at the time of presentation; had not taken antibiotics within the preceding seven days; did not have an underlying fracture; and were not pregnant as determined by history . Local anesthetics without epinephrine and high-pressure irrigation with normal saline were used for all patients . Wound scrubbing, debridement, and polyglactin subcutaneous (SQ) suture placement were carried out when necessary . Interrupted simple sutures using a monofilament, nonabsorbable material were used for skin closure . Numbered, randomized vials were given to all patients, with standardized instructions to inspect, clean, and redress their wounds three times a day . The wounds were evaluated for clinical infection at the time of follow-up . RESULTS: Among the groups, there was no difference in patient ages; gender; wound location, type, length, or depth; time elapsed from injury to ED treatment; number of wounds scrubbed or necessitating debridement; number of SQ and cutaneous sutures used; and rate of compliance with returning the used vial of dispensed topical agent . The wound infection rates for the treatment groups were: BAC, six of 109 (5.5%); NEO, five of 110 (4.5%); SIL, 12 of 99 (12.1%); and PTR, 19 of 108 (17.6%) (p = 0.0034) . CONCLUSION: The use of topical antibiotics resulted in significantly lower infection rates than did the use of a petrolatum control . BAC and NEO had the lowest wound infection rates.

Rev Laryngol Otol Rhinol (Bord), 1995, 116(2), 153 - 6
Effects of antibiotic solutions (ciprofloxacin and trimethoprim + sulfamethoxazole) on rabbit tympanic membrane; Karasolihoglu A et al.; This study was designed to assess morphological changes in the rabbit tympanic membrane after Ciprofloxacin and Trimethoprim + Sulphamethoxazole had been instilled as a single dose into the middle ear cavities of 24 rabbits . At different times the rabbits were decapitated and the lesions which occurred on the tympanic membrane were studied histopathologically . Our results indicate that in the Ciprofloxacin group reactive inflammatory changes are reversible as in the Trimethoprim + Sulphamethoxazole group.

Acta Microbiol Immunol Hung, 1995, 42(2), 171 - 7
Effects of some heavy metals on growth, pigment and antibiotic production by Streptomyces galbus; Raytapadar S et al.; A chromogenic strain of Streptomyces galbus 5ME-13 producing an antifungal antibiotic was used to study the effects of some heavy metals on growth, melanoid pigment and antibiotic production in culture . Mercury and nickel were highly toxic followed by cadmium while cobalt and chromium appeared to be less toxic . All the metals inhibited growth, pigment and antibiotic production with widely variable IC50 values . Cadmium and chromium at lower concentrations unusually stimulated growth and enhanced pigment production in the strain.

Acta Microbiol Immunol Hung, 1995, 42(2), 155 - 62
Nutrient optimization for production of broad spectrum antibiotic by Streptomyces antibioticus SR15.4; Haque SF et al.; Antibiotic production by Streptomyces antibioticus Sr15.4 was studied under various cultural conditions . During nutrient optimization it was found that the strain utilized glycerol as the best source of carbon at 1.044 molar level, and 0.020 molar arginine as the best source of nitrogen . The strain exhibited significant enhancement in antibiotic production when grown at pH 6.8.

Rapid Commun Mass Spectrom, 1995, 9(11), 1012 - 6
Multiresidue determination of quinolone antibiotics using liquid chromatography coupled to atmospheric-pressure chemical ionization mass spectrometry and tandem mass spectrometry; Doerge DR et al.; Liquid chromatography coupled to atmospheric-pressure chemical ionization mass spectrometry and tandem mass spectrometry (MS/MS) methods for the determination and quantification of four quinolone antibiotics were adapted from a published procedure for liquid-liquid extraction from catfish muscle and high-performance liquid chromatographic analysis . In-source collision-induced dissociation was used to optimize fragmentation to produce mass spectra consisting of the protonated molecule and two characteristic fragment ions of nearly equal intensity . Selected ion monitoring of three ions per quinolone yielded sensitive detection in catfish muscle extracts (estimated instrumental detection limits 0.8-1.7 ppb) . The intensity ratios were used to confirm the presence of three of the quinolones based on the accurate agreement (< or equal to 10% deviation) between ratios derived from fortified catfish extracts and those from standard quinolones . MS/MS was used to increase the specificity and sensitivity of analysis . Scans using constant neural loss (CNL) of 18 mass units gave a sensitive response for the quinolones suggesting that CNL scans may be applicable to multiresidue screening for unknown quinolones . MS/MS with multiple reaction monitoring of the {MH - 18}+ transition for each quinolone yielded the highest sensitivity analysis in catfish extracts (estimated instrumental detection limits 0.08-0.16 ppb).

Pediatr Pulmonol Suppl, 1995, 11, 68 - 9
Aerosol administration of antibiotics; Smith AL et al.; Antibiotics can be aerosolized to the lower respiratory tract of patients with pulmonary infections . With attention to stability of the antibiotic, its ability to be aerosolized, and particle size of the aerosol, rational design of an antibiotic aerosol treatment regimen is possible . The choice of nebulizer for aerosol antibiotic administration depends not only on drug stability under the nebulization conditions, but practical considerations such as ease of use in the home and expense . In general, a greater volume of respirable aerosol is generated by an ultrasonic device in comparison to the jet nebulizers . Of the factors affecting antibiotic delivery to the lower respiratory tract, the patients and their disease are the most important . This patient effect is not directly amenable to medical intervention, but can be controlled through measurement of antibiotic concentrations in respiratory secretions, seeking a target estimated from the best available in vitro data.

Microbios, 1995, 83(334), 23 - 6
Antibiotic activity of marine algae against multi-antibiotic resistant bacteria; Mahasneh I et al.; The antibiotic activity of six species of marine algae (Rhodophyta, Phaeophyta and Chlorophyta) against multi-antibiotic resistant (MAR) bacteria was investigated . The study shows that various degrees of activity were present in 18 out of the 24 algal extracts . The highest activity was for Rhodophyta (diameter of the inhibited zone ranged from 10-22 mm), whilst the lowest was for Chlorophyta (8-12 mm) . The taxonomic trends were seen between extracts, as the best solvents were found to be ether, methanol and acetone for Rhodophyta, Phaeophyta and Chlorophyta, respectively . The importance of these results on public health are discussed.

Biochem J, 1994 Dec 15, 304 ( Pt 3), 967 - 79
Binding of quinomycin antibiotic UK-65,662 to DNA: 1H-n.m.r . studies of drug-induced changes in DNA conformation in complexes with d(ACGT)2 and d(GACGTC)2; Searle MS; Quinomycin antibiotic UK-65,662 binds selectively to the 5'-CpG-binding sites of the DNA duplexes d(ACGT)2 and d(GACGTC)2; the complexes have been studied in detail by 1H-n.m.r . spectroscopy and molecular-modelling techniques employing nuclear Overhauser effect-restrained energy minimization and molecular dynamics . Whereas the terminal A.T base pairs of the tetamer duplex d(ACGT)2 adopt a stable Hoogsteen alignment (characterized by a syn glycosidic conformation of the purine base), when internalized within the hexamer duplex d(GACGTC)2, the A.T base pairs revert to anti glycosidic torsion angles characteristic of the Watson-Crick hydrogen-bonding scheme . The energetics of base-pair stacking at the terminal 5'-GpA steps of the hexamer complex, with base pairs in the Watson-Crick alignment, are concluded to be important determinants of the adopted conformation, whereas an energetic preference for stacking interactions between terminal Hoogsteen A.T base pairs and the drug quinoline chromophores is evident in the tetramer complex . The internal G.C base pairs in both complexes are highly stabilized, as indicated by the very slow exchange rates of the guanine imino protons; in contrast, the flanking A.T base pairs are no more stable than in the ligand-free DNA duplexes . A large number of intermolecular nuclear Overhauser effects are indicative of many van der Waals contacts and hydrogen-bonding between the antibiotic and the minor groove of the central G.C base pairs in both complexes, indicating that interactions with the G.C base pairs in each duplex are very similar providing the essential features for recognition and tight binding . Despite the difference in the conformation of the A.T base pairs, stacking with the quinoline rings occurs primarily with the adenine bases in both complexes . Relative intensities of intranucleotide versus internucleotide nuclear Overhauser effects indicate that both duplexes are substantially unwound by drug binding (particularly at the CpG step) and this is confirmed by the structure calculations . Both duplexes have ladder-like structures that must lead to significant local distortions of the DNA conformation in vivo.

Nucleic Acids Res, 1994 Dec 11, 22(24), 5484 - 91
NMR investigation of Hoogsteen base pairing in quinoxaline antibiotic--DNA complexes: comparison of 2:1 echinomycin, triostin A and {N-MeCys3,N-MeCys7} TANDEM complexes with DNA oligonucleotides; Addess KJ et al.; Hoogsteen base pairs have been demonstrated to occur in base pairs adjacent to the CpG binding sites in complexes of triostin A and echinomycin with a variety of DNA oligonucleotides . To understand the relationship of these unusual base pairs to the sequence specificity of these quinoxaline antibiotics, the conformation of the base pairs flanking the YpR binding sites of the 2:1 drug-DNA complexes of triostin A with {d(ACGTACGT)}2 and of the TpA specific {N-MeCys3, N-MeCys7} TANDEM with {d(ATACGTAT)}2 have been studied by 1H NMR spectroscopy . In both the 2:1 triostin A-DNA complex and the 2:1 {N-MeCys3, N-MeCys7} TANDEM-DNA complex, the terminal A.T base pairs are Hoogsteen base paired with the 5' adenine in the syn conformation . This indicates that both TpA specific and CpG specific quinoxaline antibiotics are capable of inducing Hoogsteen base pairs in DNA . However, in both 2:1 complexes, Hoogsteen base pairing is limited to the terminal base pairs . In the 2:1 triostin A complex, the internal adenines are anti and in the 2:1 {N-MeCys3, N-MeCys7} TANDEM-DNA complex, the internal guanines are anti regardless of pH, which indicates that the central base pairs of both complexes form Watson-Crick base pairs . This indicates that the sequence dependent nature of Hoogsteen base pairing is the same in TpA specific and CpG specific quinoxaline antibiotic-DNA complexes . We have calculated a low resolution three-dimensional structure of the 2triostin A-{d(ACGTACGT)}2 complex and compared it with other CpG specific quinoxaline antibiotic-DNA complexes . The role of stacking in the formation of Hoogsteen base pairs in these complexes is discussed.

Eur J Prosthodont Restor Dent, 1994 Dec, 3(2), 79 - 86
The role of antibiotics in the treatment of periodontitis . (Part I--Systemic delivery; Smith SR et al.; Controlled release devices containing tetracyclines or metronidazole are now commercially available for use in periodontal pockets . This review, in two parts, evaluates the evidence for and against using antibiotics in the treatment of periodontitis and considers the role for systemic and local delivery . Guidelines for antibiotic usage and recommended regimes are proposed.

Dig Dis Sci, 1994 Dec, 39(12), 2567 - 74
Endoscopic and histologic resolution of gastric pseudolymphoma (reactive lymphoid hyperplasia) following treatment with bismuth and oral antibiotics; Weston AP et al.; Gastric pseudolymphoma is a rare disorder of unknown etiology that can undergo transformation into malignant lymphoma . This report describes the first case of a gastric pseudolymphoma associated with Helicobacter pylori infection that underwent complete clinical, endoscopic, and histologic resolution following treatment with bismuth subsalicylate, amoxicillin, and metronidazole . The eradication of Helicobacter pylori may have eliminated ongoing antigenic stimulation that has previously been postulated to be responsible for the development and subsequent progression of gastric pseudolymphoma.

Gastroenterology, 1994 Dec, 107(6), 1835 - 8
Regression of gastric lymphoma of mucosa-associated lymphoid tissue with antibiotic therapy for Helicobacter pylori; Weber DM et al.; Regression of low-grade B cell gastric lymphoma of mucosa-associated lymphoid tissue after eradication of Helicobacter pylori with antibiotic therapy was recently shown in a small number of patients with low-volume tumors . A patient with a > 10 cm nodular gastric mucosa-associated lymphoid tissue lymphoma that caused hematemesis and weight loss is described . Antibiotic therapy of H . pylori resulted in full clinical recovery and resolution of the mass lesion and morphological features of lymphoma on routine histological examination . However, monotypic immunostaining of plasma cells persisted in a separate and grossly normal-appearing region of the stomach . Antibiotic therapy may be of benefit in patients with mucosa-associated lymphoid tissue lymphoma with mass lesions and significant signs and symptoms, but periodic search for residual lymphoma is needed.

Spine, 1994 Dec 1, 19(23), 2619 - 25
Tissue distribution of antibiotics in the intervertebral disc; Riley LH 3rd et al.; STUDY DESIGN . This study analyzed the distribution of antibiotics within the intervertebral disc of rabbits . Specimens were tested with specific antibodies against antibiotics using an immunofluorescent technique . OBJECTIVES . The results were correlated to provide a rationale for perioperative prophylaxis of infection . SUMMARY OF BACKGROUND DATA . Several groups of investigators and the recent data from our laboratory showed quantitative changes in penetration of antibiotics into intervertebral disc . No previous study has assessed antibiotic distribution in anulus fibrosus and nucleus pulposus . METHODS . Discs were obtained from rabbits after intravenous injection of penicillin or gentamicin . Antibiotics were localized in tissue sections using specific antibodies with a immunofluorescent method . RESULTS . Penicillin (negatively charged) and gentamicin (positively charged) penetrated the neutrally charged anulus fibrosus, but penicillin had less ability than gentamicin to penetrate into the negatively charged nucleus pulposus . CONCLUSION . Our data suggest that penetration and distribution of antibiotics into avascular intervertebral disc is significantly influenced by the charge of antibiotics.

Infect Dis Clin North Am, 1994 Dec, 8(4), 841 - 57
Antibiotics and sexually transmitted diseases; Bowie WR; There have been gratifying decreases in the rates of several major treatable STDs . These decreases show that diligent application of current preventive and management approaches can be effective . These improvements have not necessarily been reflected as great changes for populations at greatest risk, particularly younger women and those in certain geographic locales or in certain ethnic groups . The CDC 1993 STD guidelines provide updated recommendations for treatment, with key innovations, including an indication of the strength of evidence for certain recommendations, expanded discussions of syndromes, and modifications required in treating infection with HIV . There are many areas in which recommendations concerning efficacy are based on insufficient data . In addition to evaluation of new anti-infectives, key areas for future research are issues of compliance and effectiveness, advantages and appropriateness of liberal treatment of core group or selected populations, and impact of treatments for one STD on risk of transmission of others, particularly HIV . Further study is required on the effects of adjunctive treatments of diseases such as PID.

Analyst, 1994 Dec, 119(12), 2765 - 8
Enzyme immunoassay for the detection of isoxazolyl penicillin antibiotics in milk; Usleber E et al.; Polyclonal antibodies were raised against isoxazolyl penicillins in rabbits after immunization with a cloxacillin-human serum albumin conjugate . The antisera were tested in direct and indirect competitive enzyme immunoassays (EIAs), using glucose oxidase or horseradish peroxidase conjugates of oxacillin, cloxacillin, or dicloxacillin, respectively, as the labelled antigen . The relative cross-reactivities of each test system with oxacillin, cloxacillin, and dicloxacillin, determined from the amount of antibiotic required for 50% inhibition of labelled antigen binding, were dependent on the antibiotic used as the labelled antigen . Other beta-lactam antibiotics did not cross-react in these test systems . In a direct EIA using a cloxacillin-horseradish peroxidase conjugate, cloxacillin and dicloxacillin in milk were detected at levels of 10 and 30 ng ml-1; the average recoveries at these levels were 102 and 84%, respectively.

West J Med, 1994 Dec, 161(6), 579 - 84
Antibiotic therapy for ocular infection; Snyder RW et al.; Infections of the eye can rapidly damage important functional structures and lead to permanent vision loss or blindness . Broad-spectrum antibiotics should be administered to the appropriate site of infection as soon as a diagnosis is made . Topical drops are preferred for corneal and conjunctival infections . Intravitreal antibiotics, and possibly subconjunctival and parenteral antibiotics, are preferred for endophthalmitis . Parenteral antibiotics are recommended for infection in deep adnexal structures . We review specific aspects of antibiotic therapy for ocular and periocular infection.

Curr Opin Pediatr, 1994 Dec, 6(6), 656 - 60
Antibiotic drug allergy in children; Anderson JA; Cutaneous reactions to penicillin-type antibiotics are usually caused by IgE-mediated reactions directed toward the beta-lactam ring (in penicillin, ampicillin-amoxicillin, and cephalosporins) . These allergic reactions may be reliably diagnosed (96% to 99% of the time) with a battery of skin tests derived from penicillin . A few individuals have been identified in Spain, and now Canada, who react to side chains of the beta-lactam antibiotics (and not the beta-lactam ring) . Nonallergic cutaneous or systemic reactions to trimethoprim sulfamethoxazole (TMP-SMX) are now an emerging problem among HIV-infected patients . Life-threatening reactions have been described in HIV-infected infants who were rechallenged with TMP-SMX . New 10-day and 48-hour desensitization procedures have been used successfully in some TMP-SMX-reactive patients . Stevens-Johnson syndrome and Lyell's syndrome (toxic epidermal necrolysis) are the most serious of the antibiotic-associated cutaneous reactions . These reactions may be caused by an immune reaction similar to graft-versus-host syndrome . Corticosteroids have been shown to be helpful in the management of Stevens-Johnson syndrome . Although the mortality of toxic epidermal necrolysis is usually high, several children with this disorder have been successfully treated in a burn unit.

Gut, 1994 Dec, 35(12), 1757 - 9
Prevention of biliary stent occlusion using cyclical antibiotics and ursodeoxycholic acid; Ghosh S et al.; This study reports an open randomised controlled trial of cyclical antibiotics and ursodeoxycholic acid in prevention of plastic biliary stent occlusion . Seventy patients with malignant distal bile duct obstruction were randomised to either active treatment with cyclical antibiotics (ampicillin, metronidazole, ciprofloxacin) and ursodeoxycholic acid or no treatment after successful stent insertion . The two groups were well matched . The follow up was complete with stent occlusion or death being the end points . There was no difference in the incidence of stent occlusion between the two groups and the overall survival was similar . In conclusion, this study did not show any benefit of treatment with antibiotics and ursodeoxycholic acid in prolonging stent patency or improving survival.

Appl Environ Microbiol, 1994 Dec, 60(12), 4364 - 70
Parallel formation and synergism of hydrolytic enzymes and peptaibol antibiotics, molecular mechanisms involved in the antagonistic action of Trichoderma harzianum against phytopathogenic fungi; Schirmbock M et al.; Chitinase, beta-1,3-glucanase, and protease activities were formed when Trichoderma harzianum mycelia, grown on glucose as the sole carbon source, were transferred to fresh medium containing cell walls of Botrytis cinerea . Chitobiohydrolase, endochitinase, and beta-1,3-glucanase activities were immunologically detected in culture supernatants by Western blotting (immunoblotting), and the first two were quantified by enzyme-linked immunosorbent assay . Under the same conditions, exogenously added {U-14C}valine was incorporated in acetone-soluble compounds with an apparent M(r) of < 2,000 . These compounds comigrated with the peptaibols trichorzianines A1 and B1 in thin-layer chromatography and released {U-14C}valine after incubation in 6N HCl . Incorporation of radioactive valine into this material was stimulated by the exogenous supply of alpha-aminoisobutyric acid, a rare amino acid which is a major constituent of peptaibols . The obtained culture supernatants inhibited spore germination as well as hyphal elongation of B . cinerea . Culture supernatants from mycelia placed in fresh medium without cell walls of B . cinerea did not show hydrolase activities, incorporation of {U-14C}valine into peptaibol-like compounds, and inhibition of fungal growth . Purified trichorzianines A1 and B1 as well as purified chitobiohydrolase, endochitinase, or beta-1,3-glucanase inhibited spore germination and hyphal elongation, but at concentrations higher than those observed in the culture supernatants . However, when the enzymes and the peptaibols were tested together, an antifungal synergistic interaction was observed and the 50% effective dose values obtained were in the range of those determined in the culture supernatants . Therefore, the parallel formation and synergism of hydrolytic enzymes and antibiotics may have an important role in the antagonistic action of T . harzianum against fungal phytopathogens.

Am J Trop Med Hyg, 1994 Dec, 51(6), 797 - 9
The effect of antibiotic- and hydrocortisone-containing ointments in preventing secondary infections in guinea worm disease; Magnussen P et al.; A randomized, single-blind, controlled study comparing the efficacy of an ointment containing two antibiotics, one containing one antibiotic plus hydrocortisone, and no treatment in reducing secondary infections in patients with patent Guinea worm was undertaken in the northern region of Ghana . Seventy-seven patients were included . Time to complete healing was significantly shorter in the treatment groups compared with the controls (P = 0.044 and P = 0.003, respectively) . Secondary infections occurred more often in the controls (P = 0.00014) . Ointments containing antibiotics are recommended for application at the early stage of patent Guinea worm infection.

Biosci Biotechnol Biochem, 1994 Dec, 58(12), 2188 - 92
Nuclear magnetic resonance study and secondary structure determination of the antibiotic peptide, aibellin; Kumazawa S et al.; Aibellin is a 20-residue peptide antibiotic that has been isolated from the fungus Verticimonosporium ellipticum . Sequence-specific assignment of the 1H- and 13C-NMR signals of aibellin in a methanol solution was achieved by using the two-dimensional NMR technique . Furthermore, its secondary structure was characterized by circular dichroism (CD) and NOESY spectra . The observed NOEs, 3JNHC alpha H coupling constants and amide hydrogen-deuterium (H-D) exchange rates show that the peptide consisted of two alpha-helices and a bent structure around a Pro-14 residue.

Hepatogastroenterology, 1994 Dec, 41(6), 549 - 51
Is Crohn's disease caused by antibiotics?
Demling L.
The increase in CD that has taken place over the last 50 years has paralleled the increasing use of antibiotics in human and veterinary medicine . Insufficient doses of antibiotics can induce a capacity for toxin production in bacteria, or can make them invasive . Prior antibiotic therapy also promotes the outbreak of CD to a statistically demonstrable extent . It may clearly be assumed that CD is caused in genetically susceptible persons by intestinal bacteria whose biological (but not morphological) properties have been altered by antibiotics.

Pharmacol Res, 1994 Dec, 30(4), 289 - 99
Bacterial adhesion to respiratory mucosa and its modulation by antibiotics at sub-inhibitory concentrations; Piatti G; Respiratory infections develop after contact and successive adhesion of micro-organisms to airway mucosa . In fact, the bacterial adhesins are able to interact with a 'lock and key' mechanism with the analogous structures on epithelial surfaces when permissive conditions occur . It was observed that antibiotics at subinhibitory concentrations (sub-MICs) can modify bacterial ability of adhesion to host cells, in various ways . Bacterial adhesion is generally inhibited by antibiotics that, at these concentrations, do not kill bacteria but can change the surface architecture of the micro-organisms.

J Pharm Pharmacol, 1994 Dec, 46(12), 994 - 9
Lipophilicity of teicoplanin antibiotics as assessed by reversed phase high-performance liquid chromatography: quantitative structure-property and structure-activity relationships; Altomare C et al.; Structure-lipophilicity relationships of a large series of 63-COX teicoplanin antibiotic derivatives were examined, by correlating their capacity factors (log kw), measured through reversed-phase high-performance liquid chromatography on Deltabond C8 stationary phase, with some computed molecular properties such as fragmental log P constants (pi x), molecular volumes (Vx) and factors imparting hydrophilicity (e.g . amino groups in the X chain, nN) . A number of equations were derived which demonstrate that variations of log kw are mainly related to changes in bulk (modelled by Vx) and polarity (primarily modelled by nN) of X chains of teicoplanin derivatives . QSAR analysis revealed that in-vitro activity against E . coli increases as lipophilicity decreases and isoelectric point increases.

Int J Immunopharmacol, 1994 Dec, 16(12), 1053 - 8
Selective killing of tumor cells in vitro by immunotoxin composed of antitumor antibiotic streptonigrin and polyclonal specific antibodies; Komissarenko SV et al.; Streptonigrin N-hydroxysuccinimide ester (STN-COONSu) was obtained by carbodiimide synthesis . Poly-L-lysine (PLL) was loaded with STN-COONSu and conjugated to polyclonal rabbit immunoglobulin G (IgG) activated with sodium periodate . Non-specific IgG and IgG against Ehrlich carcinoma cells were used to construct non-specific and specific immunotoxins . Immunotoxins contained 100 molecules of streptonigrin per 1 molecule of IgG . The streptonigrin concentration that caused 50% of inhibition of {3H}thymidine incorporation in Ehrlich carcinoma cells (IC50) was 0.8 micrograms/ml for specific immunotoxin, 16 micrograms/ml for non-specific immunotoxin, and 20 micrograms/ml for the poly-L-lysine-streptonigrin conjugate (PLL-STN) used as the initial water-soluble form of antibiotic . Our results demonstrate that the toxicity for target cells of streptonigrin conjugated to specific IgG was 25 times higher than that of the initial water soluble form of antibiotic . This specific immunotoxin was non-toxic for non-target cells.

Int J Immunopharmacol, 1994 Dec, 16(12), 1035 - 42
Treatment of pregnant mice with antibiotics modulates the humoral response of the offspring: role of prenatal and postnatal factors; Dostal M et al.; This study was designed to determine the role of prenatal and postnatal factors underlying altered humoral response of the offspring of mice treated with antibiotics during pregnancy . Pregnant random-bred NMRI mice were administered i.p . from the 11th to 15th day of pregnancy with a mixture of ampicillin and cloxacillin (2:1) in a daily dose of 21 mg/kg body weight . The litters of experimental and control mothers were cross-fostered at birth and the offspring were immunized on the 23rd or 24th postnatal day with SRBC . The primary humoral response was assayed using spectrophotometric determination of SRBC lysis mediated by anti-SRBC IgM antibodies produced by spleen cells . The offspring born of saline-treated mothers and transferred to mothers treated with antibiotics, as well as the offspring born to mothers treated with antibiotics and transferred to mothers treated with saline, produced significantly higher amounts of spleen anti-SRBC IgM than the control offspring . The results suggest that the immune response of the offspring was modulated by both the prenatally and postnatally acting factors, the latter being mediated by effects of antibiotics on the maternal organism.

Biochim Biophys Acta, 1994 Nov 11, 1201(2), 149 - 56
Three-dimensional structure in solution of griseoviridin, a group A antibiotic; Jayaraman G et al.; The solution conformation of griseoviridin, a broad spectrum antibiotic, has been determined by 1H-NMR in deuterated dimethylsulfoxide . The structural determination is based on experimental data of NOE constraints Five structures were obtained from restrained molecular dynamics calculations, by imposing (the condition for) a minimum violation of distance constraints . These structures satisfy well the experimental restraints, with small values of NOE violation and total energies . On comparison with its crystal structure, a good agreement is noted with a backbone root-mean-square deviation value of 0.084 nm . However, a small variation between the structures is observed at the aminodecanoic acid part of the molecule.

J Appl Bacteriol, 1994 Nov, 77(5), 484 - 9
HM17, a new polyene antifungal antibiotic produced by a new strain of Spirillospora; Hacene H et al.; An antifungal antibiotic (HM17) was obtained from a new isolate classified to the genus Spirillospora on the basis of its chemical and morphological properties . On solid media this antibiotic strongly inhibited the growth of strains of Fusarium oxysporum formae speciales albedinis, Botrytis cinerea, Gaeumaniomyces graminis and several other fungi known to be plant and human pathogens . Antifungal activity in culture collection strains of Spirillospora has not so far been reported . The u.v . absorption spectrum and physico-chemical characteristics place HM17 in the methylpentaene sub-group of polyene macrolides . HM17 is different from other known methylpentaenes . This is the first report of polyene production by a Spirillospora.

J Antibiot (Tokyo), 1994 Nov, 47(11), 1305 - 11
Antitumor activity of SPM VIII, a derivative of the nucleoside antibiotic spicamycin, against human tumor xenografts; Kamishohara M et al.; The antitumor activity of spicamycin analogue SPM VIII against human stomach, breast, lung, colon and esophageal cancers was compared to that of mitomycin C (MMC) in the human tumor-nude mice xenograft model . Comparative studies of SPM VIII given i.v . at 6 mg/kg/day daily for 5 days and MMC given i.v . at 6.7 mg/kg on day 1 revealed that the antitumor spectrum of SPM VIII showed a different pattern from that of MMC and that SPM VIII caused tumor mass reductions in more tumors than did MMC in colon cancers (4/12 versus 1/11) . In addition to this study, a comparative study of SPM VIII given i.v . at 12 mg/kg/day 8 times at 3- or 4-day intervals and 5'-deoxy-5-fluorouridine (5'-DFUR) given po at 185 mg/kg/day 5 days per week for 4 weeks showed that SPM VIII had the highest effect on SC-9 human stomach cancer and COL-1 human colon cancer among the 3 compounds, resulting in a significant reduction of tumor mass . Although other pharmacological studies are in progress, these results suggest that SPM VIII might be a novel antitumor compound effective for human cancers including cancer of the digestive organs.

J Antibiot (Tokyo), 1994 Nov, 47(11), 1219 - 25
Cororubicin, a new anthracycline antibiotic generating active oxygen in tumor cells; Ishigami K et al.; In the course of our screening for antitumor antibiotics which show biological activities by generating active oxygen in tumor cells . Micromonospora sp . JY16 was found to produce a new anthracycline antibiotic designated cororubicin . The structure of cororubicin was elucidated as shown in Fig . 5 on the basis of NMR spectral analysis . Cororubicin generated superoxide radicals in tumor cells and showed cytotoxicity, which was reduced by addition of an antioxidative agent, dithiothreitol (DTT).

J Antibiot (Tokyo), 1994 Nov, 47(11), 1202 - 18
TAN-1496 A, C and E, diketopiperazine antibiotics with inhibitory activity against mammalian DNA topoisomerase I; Funabashi Y et al.; Fungal metabolites with an epi-oligothiadiketopiperazine structure, TAN-1496 A, C and E, were isolated from the culture broth of Microsphaeropsis sp . FL-16144 . Their molecular formulas were determined to be C22H28N2O9S2, C22H28N2O9S3 and C22H28N2O9S4, respectively . Structures were determined by comparing the NMR data with those of known diketopiperazine antibiotics, sirodesmins . These metabolites inhibited the relaxation of supercoiled pBR322 DNA by calf thymus topoisomerase I but did not affect the decatenation of kinetoplast DNA by calf thymus topoisomerase II at concentration up to 500 microM . They strongly suppressed the growth of various murine and human tumor cells and induced apoptosis . Moreover, various derivatives were synthesized to investigate the relationship of their functional groups and biological activities.

J Trauma, 1994 Nov, 37(5), 803 - 6
Prophylactic antibiotics in abdominal trauma; Sarmiento JM et al.; The study reported here evaluated the efficacy of antibiotics administered in two periods: preoperative only and additional doses postoperatively . There was no difference in developing surgical sepsis between the groups when they included antibiotics preoperatively and the severity of the trauma was minor (Abdominal Trauma Index {ATI} value < 25) . Additionally, the result was the same when one of the injured organs was the colon, in contrast with past studies . One interesting point is related to the association of a Revised Trauma Index value > 20 with a colon wound: in the present study, this combination had a deleterious effect on the patients, always resulting in abdominal sepsis . Emphasis is placed on the economic benefits of the abolition of postoperative antibiotic use in patients with ATI score less than 25.

Chest, 1994 Nov, 106(5), 1493 - 8
Preventive antibiotic usage in traumatic thoracic injuries requiring closed tube thoracostomy; Nichols RL et al.; OBJECTIVE: To evaluate the safety and effectiveness of antibiotics in reducing the infectious complications following closed tube thoracostomy for isolated chest trauma . DESIGN: Double-blind, randomized clinical trial . SETTING: Medical school affiliated large urban teaching hospital and trauma center . PATIENTS: One hundred nineteen of 159 patients over 18 years old presenting to the emergency department requiring closed tube thoracostomy for isolated chest injuries (113 penetrating, 6 blunt) . INTERVENTION: Patients received either placebo or 1 g cefonicid daily intravenously started at chest tube insertion and stopped within 24 h of removal . MEASUREMENTS AND RESULTS: The development of wound infections, pneumonia (CDC criteria), or empyema; the incidence of adverse events; length of hospitalization . One nonspecific infection was seen in the cefonicid group (1.6 percent) and six respiratory tract infections (10.7 percent) in the placebo group (three empyema, one empyema with pneumonia, two pneumonia) (p = 0.0505; p = 0.0094 {excluding nonspecific infection}) . No significant differences with antibiotic use were seen in the duration of chest tube use (p = 0.766), peak WBC counts (p = 0.108), lower peak temperatures (p = 0.063), or length of hospitalization (p = 0.165) . Patients who developed infectious complications averaged approximately 8 days longer hospitalization than those without (p < 0.0001) . CONCLUSION: This study showed that patients receiving antibiotics had a significantly reduced rate of infection than did patients administered placebo . No significant adverse events were seen in either group.

J Am Coll Surg, 1994 Nov, 179(5), 593 - 600
Prophylactic antibiotics in abdominal hysterectomy; Tanos V et al.; BACKGROUND: The cephalosporins, which have been widely used in gynecologic surgery, are considered by many to be the drug of choice for chemoprophylaxis . However, their benefit in total abdominal hysterectomy has remained controversial . This study was done to evaluate the effectiveness of the commonly used cephalosporins in preventing inflammatory complications which may occur after elective abdominal hysterectomy . STUDY DESIGN: A MEDLINE and manual review of the literature from the past 15 years (1977 to 1991), using the terms "prophylactic antibiotics," "abdominal hysterectomy," and "cephalosporins," was performed . Seventeen prospective trials using cephalosporin prophylaxis alone for 24 hours perioperatively were evaluated . A meta-analysis of the 2,752 study and control patients abstracted was performed to compare postoperative infection and febrile morbidity rates . RESULTS: The cephalosporin group as well as the various generations and individual drugs were found to be useful in preventing postoperative infection (p < 0.001) . Febrile morbidity, however, was effectively prevented (p < 0.001) by first but not by some second and third generation drugs . Multivariate analysis revealed no advantage for the newer, more expensive second and third generation cephalosporins studied . When adjusted for confounding factors, the number of doses, the amount of the dose, and the route of administration had significant impact on the outcome events . CONCLUSIONS: Chemoprophylaxis with cephalosporins was found to be effective in preventing posthysterectomy infectious complications . A single dose, preoperative injection of first (cefazolin) or second (cefoxitin) generation cephalosporin, when administrated intravenously, has been shown to yield the best, cost-effective clinical results.

Int Arch Allergy Immunol, 1994 Nov, 105(3), 308 - 16
Antiasthmatic activity of a macrolide antibiotic, roxithromycin: analysis of possible mechanisms in vitro and in vivo; Konno S et al.; This study was designed to examine the possible mechanisms by which macrolide antibiotics favorably influence the clinical course of asthmatic patients . In the first set of experiments, we investigated the effect of roxithromycin (RXM), a newly synthesized macrolide antibiotic, on in vitro cytokine secretion by mitogen-activated human peripheral blood leukocytes . RXM suppressed the secretion of T cell cytokine interleukins (IL) 2-4 and monocyte cytokine tumor necrosis factor alpha . This inhibitory effects on cytokine secretion was dose dependent and firstly noted at a concentration of as little as 0.5 microgram/ml which is much lower than therapeutic blood levels . In the second part of experiments, we examined the influence of RXM on cytokine appearance in mouse lung extract induced by lipopolysaccharide (LPS) inhalation and on bronchial responsiveness to methacholine in LPS-treated mice . As compared with mice pretreated with phosphate-buffered saline, RXM administered orally at a single dose of 5 mg/kg once a day for 21 days inhibited the appearance of IL-3, IL-4, IL-5, and tumor necrosis factor alpha in aqueous lung extracts . Pretreatment with RXM also decreased the bronchial responsiveness to methacholine induced by intratracheal injection of LPS . We conclude that the attenuating effect of macrolide antibiotics on asthmatic syndromes might be explained partially by their inhibitory effects on cytokine secretion from leukocytes.

Drug Metab Dispos, 1994 Nov-Dec, 22(6), 849 - 57
Terfenadine metabolism in human liver . In vitro inhibition by macrolide antibiotics and azole antifungals; Jurima-Romet M et al.; To determine whether the clinical adverse interactions of terfenadine with azole antifungals and macrolide antibiotics may be related to inhibition of terfenadine biotransformation, an in vitro system was developed to follow the metabolism of terfenadine by rat liver S9 or human liver microsomes . When test compounds were coincubated with terfenadine, the metabolites formed and unchanged terfenadine was quantitatively analyzed by HPLC . Five metabolites of terfenadine were formed by rat liver S9: predominantly alcohol metabolite (III), with four minor metabolites--azacyclonol (I), acid metabolite (II), an unidentified metabolite (IV), and a new ketone metabolite (V) . By human liver microsomes, two major metabolites were formed: azacyclonol (I) and alcohol metabolite (III) . Ketoconazole, fluconazole, itraconazole, erythromycin, clarithromycin, and troleandomycin potently inhibited terfenadine metabolism by human liver (IC50 = 4-10 microM), but inhibition by rat liver was weaker (IC50 = 87-218 microM) and 18% maximally for troleandomycin . Other CYP3A substrates (cyclosporin A, naringenin, and midazolam) also demonstrated potent inhibition of terfenadine biotransformation in human liver microsomes (IC50 = 17-24 microM) . Substrates of other P450 families {sparteine (CYP2D6), caffeine (CYP1A), and diclofenac (CYP2C)} only very weakly inhibited terfenadine metabolism . Dixon plot analyses for human liver revealed competitive/reversible inhibition by the azole antifungals and macrolide antibiotics of azacyclonol and alcohol metabolite formations.(ABSTRACT TRUNCATED AT 250 WORDS)

Clin Infect Dis, 1994 Nov, 19(5), 922 - 5
Delivery of antibiotics by phagocytes; Mandell GL; Mobile phagocytes, especially polymorphonuclear neutrophils, accumulate at the site of many infections . This homing activity of phagocytes can be exploited as a mechanism for the delivery of antibiotics . To be effectively transported by neutrophils, antibiotics must be concentrated in neutrophils, must not interfere with the function of neutrophils, must remain present at high concentration long enough to be transported, and must be released in active form at the site of infection . Experimental studies have demonstrated that these criteria are fulfilled by azithromycin and, to a lesser extent, by rifampin.

Mol Microbiol, 1994 Nov, 14(4), 643 - 53
afsR2: a previously undetected gene encoding a 63-amino-acid protein that stimulates antibiotic production in Streptomyces lividans; Vogtli M et al.; Earlier work has shown that the afsR genetic locus promotes formation of the pigmented antibiotics actinorhodin and undecylprodigiosin in Streptomyces lividans and its close relative, Streptomyces coelicolor . A protein designated as AfsR has been implicated in this activity . We report here the existence of a previously unknown gene, afsR2, which is separate from and adjacent to the AfsR-encoding sequence and which, when present at high copy number, (i) stimulates transcription of biosynthetic and regulatory genes in the actinorhodin gene cluster (act), and (ii) stimulates the synthesis of undecylprodigiosin . We show that the effects of afsR2 on actinorhodin synthesis are mediated through transcription of the actII-ORF4 locus, which encodes a transcriptional activator of other genes in the act cluster . Analysis of the cloned afsR2 gene indicates that its activity is the result of the 63-amino-acid protein it specifies.

Biomed Chromatogr, 1994 Nov-Dec, 8(6), 315 - 6
TLC studies on certain aminoglycoside antibiotics; Bhushan R et al.; Aminoglycoside antibiotics were separated by thin layer chromatography . Separation was achieved on untreated silica gel layers using various combinations of solvent systems, dioxane:ammonia, methanol:ammonia and propanol:ammonia . These antibiotics were visualized with the help of iodine vapours.

Am J Vet Res, 1994 Nov, 55(11), 1602 - 7
Whole-blood platelet aggregation, buccal mucosa bleeding time, and serum cephalothin concentration in dogs receiving a presurgical antibiotic protocol; Schermerhorn T et al.; Whole-blood platelet aggregation (using the impedance method) and adenosine triphosphate (ATP) release, buccal mucosal bleeding time (BT), and serum cephalothin concentration were measured in 21 adult female Beagles before (PRE) and 1 hour (1 HR) after IV administration of cephalothin (22 mg/kg) . A second injection of cephalothin (22 mg/kg) was given 3 hours after the first, and blood samples were obtained 1 hour (4 HR, 4 hours after the first injection) and 3 hours (6 HR, 6 hours after the first injection) after the second injection . Samples of jugular blood were obtained from each dog, using citrate as an anticoagulant . A platelet count was obtained for each sample . Platelet aggregation and ATP released from the aggregating platelets were measured within 1 hour of sample collection, using a whole-blood aggregometer . Adenosine diphosphate (ADP) and collagen were used as aggregating agents . Aggregation was measured over 6 minutes for each aggregating agent; ATP release in response to collagen, but not to ADP, was measured over the same period . For 1 HR samples, there was a significant (P < 0.01) reduction from PRE values in the ability of platelets to aggregate in response to ADP . Bleeding time was determined, using a published procedure, with each dog as its own control . Bleeding time during the same period was found to be significantly increased over PRE values for 1 HR (P < 0.01) and 6 HR (P < 0.02) samples . There was no significant difference between BT for 1 HR and 4 HR samples.(ABSTRACT TRUNCATED AT 250 WORDS)

Z Naturforsch {C}, 1994 Nov-Dec, 49(11-12), 772 - 4
A novel halogenated compound possessing antibiotic and cytotoxic activities isolated from the fungus Resinicium pinicola (J . Erikss.) Erikss . & Hjortst; Becker U et al.; Pinicoloform, a novel unbranched acyclic compound containing a trichloromethyl group, has been isolated from extracts of the mycelia of the Basidiomycete Resinicium pinicola . It was isolated because of its ability to induce morphological and physiological differentiation of mammalian cells, although it also exhibits antibiotic and cytotoxic activities . The structure of pinicoloform was determined by spectroscopic methods.

Ann Plast Surg, 1994 Nov, 33(5), 476 - 80
Efficacy of prophylactic antibiotics in reduction mammoplasty; Serletti JM et al.; The use of prophylactic antibiotics in reduction mammoplasty has been random and its efficacy unproven . This study reviewed 106 consecutive inferior pedicle technique reduction mammoplasties . Two groups were identified; 47 patients received prophylactic antibiotics and 59 patients did not . The decision of who received prophylactic antibiotics was random based on resident rotation and resident preoperative orders . The demographics were equal between the antibiotic group and the control group . The wound infection rate and the rate of delayed healing were examined in both groups . There were no statistically significant differences in the infection rate or the rate of delayed wound healing in either the antibiotic group or the control group . Individual risk factors were also studied in each group . These risk factors included obesity, older age, smoking history, and large reductions . The use of prophylactic antibiotics did not reduce the infection rate in any of these high-risk groups . Comparing the individual risk factors for the remainder of the patient population showed that the infection rate was higher in obese patients but was unaffected by prophylactic antibiotics . Delayed healing was also higher in larger reductions but also was unaffected by the use of prophylactic antibiotics . We conclude that the use of prophylactic antibiotics in reduction mammoplasty is not efficacious in reducing the rate of wound infection or delayed healing.

Infect Control Hosp Epidemiol, 1994 Nov, 15(11), 717 - 23
Surveillance for surgical site infections: the uses of antibiotic exposure; Yokoe DS et al.; Conventional methods of surveillance for surgical site infections are resource intensive, thus creating an incentive to develop simpler alternatives . Antibiotic exposure may serve as a satisfactory marker for a physician's belief that infection is present and, therefore, may be a more efficient, and perhaps more accurate, measure than identification of an explicit diagnosis in the medical record . Surveillance strategies that use antibiotic exposure may provide resource-efficient adjuncts for surveillance of surgical site infections or be used in selected circumstances as substitutes for conventional surveillance methods.

Infect Control Hosp Epidemiol, 1994 Nov, 15(11), 710 - 2
Drug use evaluation of antibiotics in a pediatric teaching hospital; Lee KR et al.; OBJECTIVE: To determine the incidence and type of antibiotic use variances at our institution . DESIGN: Inpatient bacterial culture and susceptibility results were reviewed for 1 week per month . Medication administration records were evaluated to determine whether antibiotic selection was appropriate, given the susceptibility of the organism . Process indicators included use of the least costly antibiotic, as well as appropriate dose, interval, and route of administration . The complete medical record was reviewed for all patients if management did not appear to meet criteria . SETTING: A 225-bed, tertiary-care children's teaching hospital . RESULTS: Thirty-five (8.2%) of 428 patients reviewed over 12 months had a total of 49 variances: failure to treat (3), treatment of contaminant/colonizer (2), use of more costly agent (10), failure to revise therapy (8), inappropriate route (2), inappropriate empiric antibiotic (4), incorrect dose (3), unnecessary multiple antibiotics (6), inappropriate drug (8), and prolonged prophylaxis (3) . CONCLUSIONS: Thirty-five patients with 10 types of variances were identified during the study . Follow-up monitoring will assess the impact of educational efforts on the incidence of variances . Specific problem antibiotics have been identified for further audits.

Pediatr Rev, 1994 Nov, 15(11), 440 - 7
Antibiotics: mechanisms of action; Woodin KA et al.; Medical practice rests on the foundation of science . Clinicians are constantly making practical decisions and dealing with immediate situations that demand solutions . Time should be taken to focus on those scientific principles that underlie our diagnostic and therapeutic maneuvers . This section of Pediatrics in Review presents selected topics that are relevant to practice from the areas of physiology, pharmacology, biochemistry, and other disciplines; clarification of these will augment the pediatrician's understanding of clinical procedures.

Public Health Rep, 1994 Nov-Dec, 109(6), 745 - 9
Antibiotic therapy for Lyme disease in Maryland; Strickland GT et al.; The recommended treatment of Lyme disease is evolving and important questions remain unanswered, such as (a) Are inexpensive oral regimens effective in curing acute illness and preventing arthritic, neurologic, and cardiac manifestations or are much more costly, and potentially toxic, intravenous antibiotics required? (b) Are relatively short 2- to 3-week courses of antibiotics sufficient or are prolonged regimens of a month, or more, better? This study reviews antibiotic therapy prescribed by Maryland physicians for the 283 cases reported in 1991 that meet the Centers for Disease Control and Prevention's case definition for Lyme disease . The purpose of the review was to obtain baseline information on the antibiotics being used by physicians in practice to treat patients that they believe have Lyme disease . The most frequently prescribed antibiotics for either the 60 percent of patients presenting with erythema migrans or the 40 percent with arthritic, neurologic, or cardiac manifestations were oral doxycycline (47 percent), tetracycline (11 percent), and amoxicillin (13 percent) . Seventy-one percent of therapeutic courses were for 2 to 3 weeks . Amoxicillin was used in two-thirds of children younger than 8 years . Sixty (21 percent) received intravenous therapy, of which ceftriaxone, with or without other antibiotics, was almost always (95 percent) used . Intravenous therapy was more frequently given to those with arthritic, neurologic, and cardiac manifestations than to those with erythema migrans (odds ratio = 3.7) and to those with these systemic symptoms along with erythema migrans than to those with erythema migrans alone (odds ratio = 3.8).(ABSTRACT TRUNCATED AT 250 WORDS)

Appl Microbiol Biotechnol, 1994 Nov, 42(2-3), 290 - 9
Phospholipase D from Streptomyces antibioticus: cloning, sequencing, expression, and relationship to other phospholipases; Iwasaki Y et al.; The extracellular phospholipase D (PLD) gene from Streptomyces antibioticus was cloned, sequenced, and expressed in Escherichia coli . Analysis of DNA sequence data revealed a putative ribosome-binding site and an open reading frame encoding a 556-amino-acid protein that included amino acid sequences obtained from the purified enzyme . The protein was expressed in an insoluble form in E . coli, but reacted with antibody against PLD . After solubilization of the protein with guanidine-HCl and 2-mercaptoethanol, subsequent dialysis restored the PLD activity . Comparison of the nucleotide sequence data with the N-terminal protein sequence indicates that this secreted protein is synthesized as a larger precursor with a 47-amino-acid N-terminal extension to the mature enzyme of 509 amino acids . The amino acid sequence of the S . antibioticus PLD was extensively compared with other PLDs and phospholipase C (PLC) . The deduced amino acid sequence of the cloned PLD was highly homologous to PLDs from S . acidomyceticus and Streptomyces sp., and contained a conserved region with S . chromofuscus PLD . From comparisons of the structural similarity and properties of the various PLDs, a classification of PLDs into two subgroups has been proposed and the highly conserved region designated tentatively region XPLD, which may be important in the catalytic function, has been identified . The homology comparison between our PLD and phosphatidylinositol-specific phospholipase C (PI-PLC) is also discussed.

Mol Gen Mikrobiol Virusol, 1994 Nov-Dec, (6), 17 - 22
{Level of sodium and potassium in Streptomyces chrysomallus subsp . macrotetrolidi cells--producers of macrotetralide antibiotics}; Sverdlova AN et al.; The ionophoretic macrotetrolide antibiotics selective to monovalent cations K+ and mainly to NH4+ were determined during the lag period of culture growth . At this stage the cells contain the maximal amounts of Na+ and K+ . Macrotetrolides, whose selectivity to Na+ and K+ varies, can regulate the intracellular content of these cations by participating in the cation transport . The authors propose that the cells possess furosemide sensitivity and K+/Na+ ATPase transport systems.

Pflugers Arch, 1994 Nov, 429(1), 146 - 9
Expression cloning of a cDNA from rabbit small intestine related to proton-coupled transport of peptides, beta-lactam antibiotics and ACE-inhibitors; Boll M et al.; Injection of poly(A)+ RNA from rabbit small intestine into Xenopus laevis oocytes resulted in expression of pH dependent transport of the aminocephalosporin cefadroxil . A cDNA library constructed from a 2.2 to 5 kb fraction was screened for expression of cefadroxil transport after injection of the corresponding cRNA synthetized in vitro from different pools of clones . The single clone identified stimulated uptake of cefadroxil into oocytes about 50-fold at pH 6.5 . Kinetic analysis of expressed transport activity revealed a saturable transport system shared by amino beta-lactam antibiotics, dipeptides and selected angiotensin converting enzyme inhibitors . Evidence for rheogenic cefadroxil/H(+)-cotransport was obtained by a) The demonstration that cefadroxil influx increased the inward current in oocytes clamped at a holding potential of -60 mV in sodium-free medium and b) A decrease of intracellular pH in oocytes caused by cefadroxil uptake . Current-voltage relationships in the presence of glycylsarcosine or cefadroxil showed that transport activity is dependent on the membrane potential . Sequencing of the cDNA revealed its identity with the recently cloned peptide transporter from rabbit small intestine designated PepT1.

J Antimicrob Chemother, 1994 Nov, 34(5), 669 - 78
Automatic procedures for measuring post-antibiotic effect and determining random errors; Jason AC et al.; Four methods are described for determining the post-antibiotic effect (PAE) automatically using the high resolution capabilities of the conductance measurement of bacterial growth . The time resolution of each method is derived by a statistical procedure for calculating random error from the component errors involved in each determination . The procedures are illustrated using data generated from the measurements of the growth of Escherichia coli NCTC 4174 after exposure of cultures to five antibiotic concentrations . Excellent agreement was found to exist between three of the four methods . However, that based on the determination of the time of peak growth rate is shown to provide better resolution than the other methods, i.e., those based on growth to 10(7) organisms/mL, the duration of the lag phase or the mean retardation of growth averaged over the entire period of observation . The results strongly suggest that PAE may be ascribed entirely to a prolongation of lag time.

Biochemistry, 1994 Oct 18, 33(41), 12397 - 404
Sequence specificity of quinoxaline antibiotics . 2 . NMR studies of the binding of {N-MeCys3,N-MeCys7}TANDEM and triostin A to DNA containing a CpI step; Addess KJ et al.; The binding of CysMeTANDEM and triostin A to DNA containing a CpI step has been studied by one- and two-dimensional 1H NMR spectroscopy . CysMeTANDEM binds sequence specifically to CpI steps as well as TpA steps as a bis-intercalator with the peptide backbone in the minor groove of the DNA . Only nonspecific, nonintercalative binding is observed between triostin A and DNA containing a CpI step . Comparison of the CysMeTANDEM-{d(GGACITCC)}2 complex to the CysMeTANDEM-{d(GGA-TATCC)}2 complex indicates that the structures of both complexes are very similar . However, CysMeTANDEM binds less tightly to {d(GGACITCC)}2 than to {d(GGATATCC)}2 . The NMR evidence presented provides molecular insight into the role of stacking interactions and hydrogen bonding between the drug and the DNA in the sequence-specific binding of CysMeTANDEM to TpA sites and of triostin A to CpG sites.

Biochemistry, 1994 Oct 18, 33(41), 12386 - 96
Sequence specificity of quinoxaline antibiotics . 1 . Solution structure of a 1:1 complex between triostin A and {d(GACGTC)}2 and comparison with the solution structure of the {N-MeCys3,N-MeCys7}TANDEM-{d(GATATC)}2 complex; Addess KJ et al.; Triostin A, a naturally occurring quinoxaline antibiotic that contains N-methyl groups on the valine and cysteine residues, binds sequence specifically to DNA at NCGN sites . {N-MeCys3,N-MeCys7}-TANDEM (CysMeTANDEM), a synthetic quinoxaline antibiotic, differs in its chemical structure from triostin A only at the valine residues, which contain no N-methyl substituents . CysMeTANDEM has a sequence specificity different from triostin A, binding specifically to DNA at NTAN sites . To understand the factors that determine the sequence specificity of these quinoxaline antibiotics, the solution structure of a 1:1 complex of triostin A with the DNA hexamer {d(GACGTC)}2 has been determined using NMR-derived distance and dihedral angle restraints . The solution structure of the triostin A-{d(GACGTC)}2 complex is compared directly to the solution structure of a 1:1 complex of CysMeTANDEM with {d(GATATC)}2 and is also compared to the crystal structure of 2:1 complex of triostin A with {d(CGTACG)}2 . Triostin A binds to {d(GACGTC)}2 as a bis-intercalator around the CpG step, and the peptide ring of the drug binds in the minor groove of the DNA . The central C.G base pairs of the complex are underwound with an average helical twist angle of approximately -9.0 degrees and buckle inward by about 25 degrees . There are intermolecular hydrogen bonds between each of the Ala NH and the GN3 protons of the CpG binding site . Similar structural features are observed in the solution structure of the CysMeTANDEM-{d(GATATC)}2 complex . However, in the structure of the triostin A-{d(GACGTC)}2 complex, two intermolecular hydrogen bonds between each of the Ala CO oxygens of the drug and the 2-amino protons of guanine are observed . These hydrogen bonds do not form in the CysMeTANDEM-DNA complex . Instead, CysMeTANDEM contains two intramolecular hydrogen bonds between the Ala CO atoms and the Val amide protons, making the Ala CO atoms unavailable to form two intermolecular hydrogen bonds . The role of these intermolecular hydrogen bonds in the CpG specificity of triostin A is discussed.

Med J Aust, 1994 Oct 17, 161(8), 491 - 3
Antibiotic and benzodiazepine prescribing by general practice trainees; Zwar NA et al.; OBJECTIVE: To study the prescribing of antibiotics and benzodiazepines by a group of general practice trainees . METHODS: Forty-six trainees in their general practice term with the Royal Australian College of General Practitioners Training Program and 495 experienced general practitioners were compared with regard to patients managed, prescribing of antibiotics for respiratory tract infections and prescribing of benzodiazepines for anxiety, sleep disorders and depression . RESULTS: Trainees saw more young patients and patients with acute respiratory infections, and fewer patients with psychological problems, than the experienced practitioners . Trainees prescribed antibiotics less often for undifferentiated upper respiratory tract infection and their prescribing for tonsillitis was more frequently in agreement with prescribing guidelines . Trainees were less likely to prescribe a benzodiazepine for anxiety or sleep problems . CONCLUSIONS: General practice trainees were relatively conservative prescribers of antibiotics and benzodiazepines . At times both groups did not prescribe in accordance with antibiotic prescribing guidelines and an appreciable number of patients continue to be prescribed benzodiazepines on a long term basis.

FEMS Microbiol Lett, 1994 Oct 15, 123(1-2), 11 - 8
Mycobacterial cell wall: structure and role in natural resistance to antibiotics; Jarlier V et al.; Mycobacteria show a high degree of intrinsic resistance to most antibiotics and chemotherapeutic agents . The low permeability of the mycobacterial cell wall, with its unusual structure, is now known to be a major factor in this resistance . Thus hydrophilic agents cross the cell wall slowly because the mycobacterial porin is inefficient in allowing the permeation of solutes and exists in low concentration . Lipophilic agents are presumably slowed down by the lipid bilayer which is of unusually low fluidity and abnormal thickness . Nevertheless, the cell wall barrier alone cannot produce significant levels of drug resistance, which requires synergistic contribution from a second factor, such as the enzymatic inactivation of drugs.

Biochim Biophys Acta, 1994 Oct 6, 1214(3), 221 - 8
Purification and properties of phosphatidylinositol-specific phospholipase C from Streptomyces antibioticus; Iwasaki Y et al.; A novel type of phosphatidylinositol-specific phospholipase C (PI-PLC) was purified from culture supernatant of a strain of Actinomycetales, Streptomyces antibioticus . The purified enzyme showed a single band on native polyacrylamide gel electrophoresis (native PAGE) with a molecular weight of 32 kDa, but showed two polypeptides, named alpha- and beta-peptides, on sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) with molecular weights of 23 kDa and 15 kDa, respectively . From the results of both electrophoretic analysis and N-terminal amino acid sequencing, it was estimated that the enzyme was composed of alpha- and beta-peptides . The enzyme could hydrolyze phosphatidylinositol, but not any other glycerophospholipids . The enzyme had pH and temperature optima at around 7.0 and 30 degrees C, respectively, and was stable up to 50 degrees C when incubated at pH 8.0 for 30 min . The PI-PLC was strongly activated by SDS, sodium deoxycholate (SDC) and diethyl ether, but not by Triton X-100, and inhibited by cetylpyridinium chloride (CPC) . The enzyme was activated a little by Ca2+ and was inhibited completely by a chelating agent such as ethylenediaminetetraacetic acid (EDTA) and glycoletherdiaminetetraacetic acid (EGTA) . Their inhibitions were restored by the addition of Ca2+, suggesting that a certain amount of Ca2+ is essential for the enzymatic activity.

J Appl Bacteriol, 1994 Oct, 77(4), 426 - 32
Characterization of an antibiotic produced by Alteromonas luteoviolacea Gauthier 1982, 85 isolated from Kinko Bay, Japan; McCarthy SA et al.; An antibiotic produced by Alteromonas luteoviolacea strain 9K-V10 was recovered after cold acetone precipitation of culture supernatant fluids or lysates that had been frozen and thawed . The precipitate obtained from cell-free lysates was fractioned by DEAE ion-exchange chromatography . Further purification by gel-filtration chromatography yielded a single peak of antibiotic activity that corresponded to a protein peak with a molecular mass of approximately 100 kDa . After non-denaturing polyacrylamide gel electrophoresis, antibiotic activity co-migrated with a protein band . The isoelectric point of the antibiotic was estimated to be 7.7 . Treatment of the concentrated active fraction with proteinase K or heating at 70 degrees C for 10 min resulted in total loss of antibiotic activity . These results show that the antibiotic produced by Alt . luteoviolacea 9K-V10 is of a proteinaceous nature.

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