Antibiotics

Pediatr Ann, 1996 Nov, 25(11), 639 - 45
Continuation of antibiotic therapy for serious bacterial infections outside of the hospital; Gutierrez K; Many children hospitalized with serious bacterial infections are candidates for either home oral antibiotic therapy or outpatient parenteral antibiotic therapy . Outpatient antibiotic therapy offers the potential for excellent medical treatment, reduced costs, and improved quality of life for ill children . However, cost considerations must not override good medical judgment . Certain children simply are not candidates for outpatient therapy because of the seriousness of their infection, poor compliance, lack of intravenous access, or poor social situation . In addition, although the few published studies to date all show that outpatient antibiotic therapy is effective, there is further need for properly designed clinical trials to evaluate the efficacy and safety of outpatient antibiotic therapy for serious bacterial infections in children.

Pediatr Ann, 1996 Nov, 25(11), 614 - 7
Use of generic antibiotics in children; Tam J; Most oral antibiotics have highly acceptable generic equivalents . The generic products are comparable in bioavailability, side-effect profile, and efficacy to their brand-name equivalents . Some are more palatable, and all are less costly that the trade-name products . Increased use of oral generic antibiotics will generate significant cost savings for both the patients and prescribers, without compromising therapeutic benefits.

Transfusion, 1996 Nov-Dec, 36(11-12), 952 - 4
Influence of antibiotics on posttransfusion platelet increment; Bock M et al.; BACKGROUND: Fever has been identified as a major cause of platelet refractoriness . However, it is regularly attended by the administration of antibiotics, and thus it cannot be determined whether fever, the administration of antibiotics, or both are responsible for the reduced platelet increment . The present study was undertaken to discern the effect of body temperature and antibiotics on transfusion success . STUDY DESIGN AND METHODS: Single-donor platelet transfusions (n = 400) were monitored retrospectively . Besides other influencing factors (e.g., spleen size, number of previous transfusions, diagnosis, bone marrow transplantation), body temperature and the administration of antibiotics were documented from the patients' records . To distinguish the effects of fever and antibiotics, a general mixed model of variance was used for analysis . RESULTS: Besides the well-known factors of splenomegaly, hepatomegaly, bone marrow transplantation, and pretransfusion storage time, both body temperature and antibiotics independently reduced the corrected count increment . Among the various antibiotics, amphotericin B, ciprofloxacin, and vancomycin had the greatest influence . CONCLUSION: The administration of antibiotics has a negative effect on the corrected count increment, independent of the presence of fever . Besides amphotericin B, which has previously been shown to influence the corrected count increment, vancomycin and ciprofloxacin reduce it significantly . Because these antibiotics are widely used in patients with bone marrow failure, these observations should be proven by further prospective in vivo and in vitro studies.

Clin Infect Dis, 1996 Nov, 23(5), 1165 - 7
Disseminated and cerebral infection due to Nocardia farcinica: diagnosis by blood culture and cure with antibiotics alone; Peters BR et al.; Systemic infections with Nocardia species continue to be a serious threat to immunosuppressed hosts . Diagnosis of these infections can be difficult despite their known tendency for cerebral and subcutaneous involvement . We describe a patient who presented with nonspecific constitutional symptoms and was found to have subcutaneous and cerebral abscesses due to Nocardia farcinica . In addition, a blood culture yielded the organism . The patient responded remarkably to oral therapy; resolution of the cerebral disease was observed on serial magnetic resonance images . We discuss the important clinical features on N . farcinica infection, the rarity of positive blood cultures, and the importance of susceptibility testing of Nocardia species in selecting drug therapy.

Antimicrob Agents Chemother, 1996 Nov, 40(11), 2669 - 70
In vitro activities of azithromycin, clarithromycin, and other antibiotics against Chlamydia pneumoniae; Kuo CC et al.; The in vitro susceptibilities of Chlamydia pneumoniae isolates to macrolide, tetracycline, and quinolone antibiotics were determined . Tetracycline, clarithromycin, and erythromycin had the lowest MICs in the first cell culture passage . Azithromycin required the lowest concentration for complete inhibition of inclusion formation on the second pass into antibiotic-free medium, likely reflecting its high intracellular concentrations.

Arch Surg, 1996 Nov, 131(11), 1165 - 71; discussion 1171-2
Does intraoperative blood loss affect antibiotic serum and tissue concentrations?
Swoboda SM, Merz C, Kostuik J, Trentler B, Lipsett PA.
OBJECTIVE: To determine the effect of intraoperative blood loss on prophylactic cefazolin and gentamicin serum and tissue concentrations . DESIGN: A prospective study of elective spinal instrumentation surgical procedures with an expected large blood loss . SETTING: Tertiary care, inner-city university hospital . PATIENTS: Eleven adult patients who underwent an elective surgical procedure that involved spinal instrumentation . INTERVENTION: Standard perioperative administration of a combination of cefazolin and gentamicin . Serum and tissue samples were obtained consecutively throughout the surgical procedure . MAIN OUTCOME MEASURES: The effect of intraoperative blood loss on serum and tissue cefazolin and gentamicin concentrations and their pharmacokinetics . RESULTS: At the time of the incision, serum cefazolin concentrations were greater than tissue concentrations (P = .07) . A mean dose of 1.8-mg/kg gentamicin yielded low or nontherapeutic serum and tissue gentamicin concentrations . Cefazolin and gentamicin were eliminated from the tissue compartment slower than from the serum compartment (P < .03), while the half-life of cefazolin was significantly (P = .06) longer in the tissue compartment . The volume of distribution of cefazolin was normal (ie, 12.5 L), while the volume of distribution of gentamicin was 5-fold greater than expected . At 60 minutes after the incision, blood loss correlated with cefazolin tissue concentrations (r = -0.66, P = .05) . Blood loss correlated with the change in tissue antibiotic concentrations for cefazolin (r = 0.73, P = .04) . In addition, the clearance of gentamicin from the tissues correlated with blood loss (r = 0.82, P = .01) . CONCLUSIONS: Based on measured pharmacokinetic values, additional doses of cefazolin should be administered when the operation exceeds 3 hours and blood loss is greater than 1500 mL . Doses of gentamicin greater than 1.8 mg/kg should be administered more than 30 minutes prior to the surgical incision.

J Clin Invest, 1996 Nov 1, 98(9), 2066 - 75
The antifungal antibiotic, clotrimazole, inhibits Cl- secretion by polarized monolayers of human colonic epithelial cells; Rufo PA et al.; Clotrimazole (CLT) prevents dehydration of the human HbSS red cell through inhibition of Ca++-dependent (Gardos) K+ channels in vitro (1993 . J . Clin Invest . 92:520-526.) and in patients (1996 . J . Clin Invest . 97:1227-1234.) . Basolateral membrane K+ channels of intestinal crypt epithelial cells also participate in secretagogue-stimulated Cl- secretion . We examined the ability of CLT to block intestinal Cl- secretion by inhibition of K+ transport . Cl- secretion was measured as short-circuit current (Isc) across monolayers of T84 cells . CLT reversibly inhibited Cl- secretory responses to both cAMP- and Ca2+-dependent agonists with IC50 values of approximately 5 microM . Onset of inhibition was more rapid when CLT was applied to the basolateral cell surface . Apical Cl- channel and basolateral NaK2Cl cotransporter activities were unaffected by CLT treatment as assessed by isotopic flux measurement . In contrast, CLT strongly inhibited basolateral 86Rb efflux . These data provide evidence that CLT reversibly inhibits Cl- secretion elicited by cAMP-, cGMP-, or Ca2+-dependent agonists in T84 cells . CLT acts distal to the generation of cAMP and Ca2+ signals, and appears to inhibit basolateral K+ channels directly . CLT and related drugs may serve as novel antidiarrheal agents in humans and animals.

Obstet Gynecol, 1996 Nov, 88(5), 801 - 5
Preterm premature ruptured membranes: a randomized trial of steroids after treatment with antibiotics; Lewis DF et al.; OBJECTIVE: To assess the effectiveness of corticosteroids in patients with preterm premature rupture of membranes (PROM) after treatment with a broad-spectrum antibiotic, ampicillin-sulbactam . METHODS: A randomized clinical trial of corticosteroids in patients with preterm PROM was undertaken after treating these patients for a minimum of 12 hours with ampicillin-sulbactam . No digital vaginal examinations were performed on these patients . Antibiotics were continued for 7 days and the steroids were repeated weekly . No tocolytics were used . The primary outcome measure was the incidence of respiratory distress syndrome (RDS) . Secondary outcome measures included latency period and neonatal and maternal infectious morbidity . RESULTS: Seventy-seven patients were enrolled and data about their pregnancies were analyzed . No statistically significant difference in latency period was noted (14.7 days in the steroid group, 15.8 days in the no-steroid group) . Both neonatal and maternal infectious morbidity were similar . A significant reduction in the incidence of RDS (18.4 versus 43.6%, P = .03) were observed in the steroid group . CONCLUSION: These data suggest that treating preterm PROM patients with a broad-spectrum antibiotic before corticosteroids decreases RDS without apparent adverse sequelae.

Mol Biochem Parasitol, 1996 Oct 30, 81(2), 127 - 36
An antibiotic, ascofuranone, specifically inhibits respiration and in vitro growth of long slender bloodstream forms of Trypanosoma brucei brucei; Minagawa N et al.; Ascofuranone, a prenylphenol antibiotic isolated from a phytopathogenic fungus, Ascochyta visiae, strongly inhibited both glucose-dependent cellular respiration and glycerol-3-phosphate-dependent mitochondrial O2 consumption of long slender bloodstream forms of Trypanosoma brucei brucei . This inhibition was suggested to be due to inhibition of the mitochondriai electron-transport system, composed of glycerol-3-phosphate dehydrogenase (EC 1.1.99.5) and plant-like alternative oxidase . Ascofuranone noncompetitively inhibited the reduced coenzyme Q1-dependent O2 uptake of the mitochondria with respect to ubiquinol (Ki = 2.38 nM) . Therefore, the susceptible site is deduced to be the ubiquinone redox machinery which links the two enzyme activities . Further, ascofuranone in combination with glycerol completely blocked energy production, and potently inhibited the in vitro growth of the parasite . Our findings suggest that ascofuranone might be a promising candidate for the chemotherapeutic agents of African trypanosomiasis.

Gene, 1996 Oct 24, 177(1-2), 217 - 22
Cloning, sequencing, overexpression in Escherichia coli, and inactivation of the valine dehydrogenase gene in the polyether antibiotic producer Streptomyces cinnamonensis; Leiser A et al.; The catabolism of branched chain amino acids, especially valine, appears to play an important role in furnishing building blocks for macrolide antibiotic biosynthesis . To determine for the first time the importance of valine dehydrogenase (vdh) in polyether antibiotic biosynthesis, the vdh gene from Streptomyces cinnamonensis has been cloned and sequenced . The enzyme (M(r)37,718 Da) has been produced in large amounts in an active form in the E . coli cytoplasm using a T7 RNA-polymerase expression system . Upon inactivation of the gene in S . cinnamonensis by a double-crossover mechanism, a hyg::vdh mutant was isolated that was devoid of vdh activity . Upon growth in chemically defined media, as well as a complex medium optimised for monensin production, the mutant and wild-type grew equally well and reached the same levels of monensin production . In both strains a valine transaminase activity could be detected that provides an alternative route for converting valine into 2-oxoisovaleric acid . The results show that vdh is not essential for normal growth of S . cinnamonensis, and its inactivation does not significantly affect normal levels of monensin production in this strain.

J Biol Chem, 1996 Oct 11, 271(41), 25369 - 74
The antibiotic bicyclomycin affects the secondary RNA binding site of Escherichia coli transcription termination factor Rho; Magyar A et al.; The interaction of Rho and the antibiotic bicyclomycin was probed using in vitro transcription termination reactions, poly(C) binding assays, limited tryptic digestions, and the bicyclomycin inhibition kinetics of ATPase activity in the presence of poly(dC) and ribo(C)10 . The approximate I50 value for the bicyclomycin inhibition of transcription termination at Rho-dependent sites within a modified trp operon template was 5 microM . At antibiotic concentrations near the I50 value, bicyclomycin inhibition of Rho-dependent transcripts was accompanied by the appearance of a new set of transcripts whose size was midway between the Rho-dependent transcripts and the readthrough transcripts . Bicyclomycin did not inhibit poly(C) binding to Rho . In the presence of poly(dC), bicyclomycin showed a reversible mixed inhibition of the ribo(C)10-stimulated ATPase activity . The extrapolated Ki for bicyclomycin was 2.8 microM without ribo(C)10 and increased to 26 microM in the presence of ribo(C)10 . Correspondingly, the Km(app) for ribo(C)10 without bicyclomycin was 0.8 microM and with bicyclomycin was 5 microM at infinite inhibitor concentration . The data suggested that the antibiotic binds to Rho, influencing the secondary RNA binding (tracking) site on Rho and slows the tracking of Rho toward the bound RNA polymerase.

FEBS Lett, 1996 Oct 7, 394(3), 307 - 10
Hyperactivity of cathepsin B and other lysosomal enzymes in fibroblasts exposed to azithromycin, a dicationic macrolide antibiotic with exceptional tissue accumulation; Gerbaux C et al.; Azithromycin accumulates in lysosomes where it causes phospholipidosis . In homogenates prepared by sonication of fibroblasts incubated for 3 days with azithromycin (66 microM), the activities of sulfatase A, phospholipase A1, N-acetyl-beta-hexosaminidase and cathepsin B increased from 180 to 330%, but not those of 3 non-lysosomal enzymes . The level of cathepsin B mRNA was unaffected . The hyperactivity induced by azithromycin is non-reversible upon drug withdrawal, prevented by coincubation with cycloheximide, affects the Vmax but not the Km, and is not reproduced with gentamicin, another drug also causing lysosomal phospholipidosis . The data therefore suggest that azithromycin increases the level of lysosomal enzymes by a mechanism distinct from the stimulation of gene expression but requiring protein synthesis, and is not in direct relation to the lysosomal phospholipidosis.

J Antibiot (Tokyo), 1996 Oct, 49(10), 980 - 4
Studies on new antitumor antibiotics, leptofuranins A, B, C and D II . Physiocochemical properties and structure elucidation; Hayakawa Y et al.; The structures of new antitumor antibiotics, leptofuranins A, B, C and D were elucidated to be as shown in Fig . 1 by NMR spectral analysis including a variety of two-dimensional techniques . The leptofuranins are novel leptomycin-related substances containing a tetrahydrofuran ring . Leptofuranins C and D were revealed to be in tautomeric isomerism and their relative stereochemistries were analyzed by NOESY experiments.

Arch Fam Med, 1996 Oct, 5(9), 523 - 6
Antibiotic use during the first 200 days of life; Bergus GR et al.; To examine the use of antibiotics by infants in eastern Iowa, longitudinal data were collected from a cohort recruited at birth from 8 hospitals . Parents of recruited children were mailed questionnaires 6 weeks, 3 months, and 6 months after birth . Cumulative rates of use were determined by means of life tables for any antibiotic as well as by type of antibiotic . Factors associated with antibiotic use and patterns of use were also determined . There were data for 789 children . Antibiotic use was common in our cohort and increased with age . At 50, 100, 150, and 200 days of life, 8.7%, 26.7%, 37.3%, and 70.5%, respectively, of the infants had used at least 1 antibiotic . Infants were most frequently treated with amoxicillin, followed by cephalosporins and sulfonamides . Otitis media was the illness that most commonly prompted the use of an antibiotic.

Fam Pract, 1996 Oct, 13(5), 445 - 9
Are antibiotics over-prescribed in Poland? Management of upper respiratory tract infections in primary health care region of Warszawa, Wola; Windak A et al.; BACKGROUND: Concern about the increasing numbers of multiple resistant strains resulting from over- and misuse of antibiotics is growing world-wide . METHOD: A questionnaire based on two cases related to respiratory tract infections for which antibiotic prescription was disputable was sent to primary care physicians in the health care district of Warszawa, Wola, Poland . RESULTS: The prescription percentage for both cases was high, with a large variety in choice of antibiotic therapy made by the doctors . This finding was striking when compared with the more restrictive prescription behaviour of Dutch general practitioners . Moreover, this high prescription percentage was combined with other abundant activities . In the case of the patient with acute tonsillitis, 53% of the primary care physicians would have ordered additional tests, 94% would have advised bed-rest and 9% would have referred . In the sinusitis case, these figures were 88, 74 and 54% respectively . No correlations were found between choice of antibiotics and characteristics of the physicians such as age, gender, experience with working in primary health care or degree of specialization . CONCLUSIONS: In conclusion, the results of this small pilot study indicate that Polish first-contact doctors have an inadequate prescription behaviour in cases with upper respiratory tract infections . Our results underline the need for courses in pharmacotherapy within the postgraduate education course in family medicine recently introduced in Poland.

Clin Podiatr Med Surg, 1996 Oct, 13(4), 683 - 99
The use of oral antibiotics in lower-extremity infections; Joseph WS et al.; It is estimated that American podiatrists write 78,000 prescriptions per week for oral antibiotics . This article discusses the currently available oral antibiotics and their appropriate usage in podiatric medicine.

Chest, 1996 Oct, 110(4), 965 - 71
A prospective randomized study of inpatient iv . antibiotics for community-acquired pneumonia . The optimal duration of therapy; Siegel RE et al.; STUDY OBJECTIVE: To compare therapeutic outcome and perform a cost-benefit analysis of inpatients with community-acquired pneumonia (CAP) treated with a shortened course of i.v . antibiotic therapy . DESIGN: A prospective, randomized, parallel group study with a follow-up period of 28 days . SETTING: Bronx Veterans Affairs Medical Center (VAMC) and the Castle Point VAMC; university-affiliated VAMC general medical wards from September 1993 to March 1995 . PATIENTS: Seventy-two male veterans and 1 female veteran with 75 episodes of CAP defined by a new infiltrate on chest radiograph and either history or physical findings consistent with pneumonia . Study population was 42%(31) black, 33%(24) white, and 25%(18) Hispanic . INTERVENTIONS: Patients were randomized (1:1:1) to 1 of 3 treatment groups: group 1 received 2 days of i.v . and 8 days of oral therapy; group 2 received 5 days of i.v . and 5 days of oral therapy; and group 3 received 10 days of i.v . therapy . Antibiotics consisted of cefuroxime, 750 mg every 8 h for the i.v . course, and cefuroxime axetil, 500 mg every 12 h for the oral therapy . MEASUREMENTS AND RESULTS: No differences were found in the clinical course, cure rates, or resolution of chest radiograph abnormalities among the three groups . A significant difference was found in the length of stay (LOS) among the three groups . The mean +/- SD LOS was 6 +/- 3 days in group 1, 8 +/- 2 days in group 2, and 11 +/- 1 days in group 3 . The shortened LOS could potentially save $95.5 million for the Department of Veterans Affairs and $2.9 billion for the US private sector . CONCLUSIONS: Adult patients hospitalized for CAP who are not severely ill can be successfully treated with an abbreviated (2-day) course of i.v . antibiotics and then switched to oral therapy . A longer course of i.v . therapy prolongs hospital stay and cost, without improving the therapeutic cure rate.

Nucleic Acids Res, 1996 Oct 1, 24(19), 3700 - 6
An antibiotic-binding motif of an RNA fragment derived from the A-site-related region of Escherichia coli 16S rRNA; Miyaguchi H et al.; A small RNA derived from the decoding region of Escherichia coli 16S rRNA can bind to antibiotics of aminoglycosides (neomycin and paromomycin) that act on the small ribosomal subunit {Purohit,P . and Stern,S . (1994) Nature, 370, 659-662} . In the present study, the P-site subdomain was removed from this decoding region RNA to construct a 27mer RNA (designated as ASR-27), which includes the A-site-related region (positions 1402-1412 and 1488-1497) of 16S rRNA . Footprint experiments with dimethyl sulfate as a chemical probe indicated that the ASR-27 RNA can interact with the neomycin family in the same manner as the decoding region RNA . A mutagenesis analysis of the ASR-27 RNA revealed that paromomycin binding of ASR-27 involves the C1407.G1494 and C1409-G1491 base pairs, and the internal loop comprising A1408 and the nucleotides in positions 1492-1493, located between the two C.G base pairs . In addition, a G or U in position 1495, and base pairing between positions 1405 and 1496 are also involved . These structural features were found in a viral RNA element, the Rev-binding site of human immunodeficiency virus type-1, which may explain why neomycin can bind to this viral RNA.

Biotechnol Appl Biochem, 1996 Oct, 24 ( Pt 2), 139 - 43
Dynamic reaction design of enzymic biotransformations in organic media: equilibrium-controlled synthesis of antibiotics by penicillin G acylase; Fernandez-Lafuente R et al.; Parameters relevant to the thermodynamically controlled synthesis of cephalothin utilizing highly active stabilized penicillin G acylase derivatives were studied . These included solubility/stability of substrates, enzyme derivative activity/stability, reaction course and synthetic yields . These parameters were altered by varying the pH, dimethylformamide concentration and temperature . Simultaneous optimization of the selected parameters could not be achieved with a single set of conditions . However, continuous adjustment of conditions throughout the reaction course allowed each parameter to be optimized (dynamic reaction design) . This strategy works by optimizing those parameters that are critical to the overall reaction at a given point, whilst leaving others sub-optimal when their contribution to the total is minimal . This strategy has achieved a 90% transformation of antibiotic nucleus to cephalothin at a final concentration of 20 g/l, high enzyme and reactant stability, with a reaction period of 3 h (using 1 ml of derivative/40 ml of reaction solution).

Br J Haematol, 1996 Oct, 95(1), 33 - 8
Effects of immunosuppressive drugs and antibiotics on GM-CSF and G-CSF secretion in vitro by monocytes, T lymphocytes and endothelial cells; Lenhoff S et al.; We studied the effects of eight antibiotics, cyclosporin and corticosteroids on the in vitro secretion of GM-CSF and G-CSF by monocytes . T lymphocytes and endothelial cells . The aim was to evaluate a possible mechanism for these drugs in the delay of haemopoietic recovery after high-dose chemotherapy or bone marrow transplantation . Corticosteroids were prominent inhibitors of GM-CSF secretion by monocytes and T lymphocytes, but not by endothelial cells . In contrast, G-CSF secretion by monocytes was unchanged whereas that of endothelial cells was enhanced in the presence of corticosteroids . Cyclosporin efficiently down-regulated GM-CSF secretion by T lymphocytes and had also a minor effect on CSF secretion by endothelial cells, whereas monocyte secretion was unaffected . Stimulated T lymphocytes derived from patients under treatment with cyclosporin had impaired capacity to secrete GM-CSF compared to controls . Among the antibiotics, cephalosporins inhibited GM-CSF secretion by T lymphocytes, and GM- and G-CSF secretion by endothelial cells . Ciprofloxacin and sulphmethoxazole had minor effects on GM-CSF secretion by T lymphocytes and endothelial cells . No antibiotic significantly influenced GM-CSF secretion by monocytes.

FEMS Microbiol Lett, 1996 Oct 1, 143(2-3), 133 - 9
Topological studies of the membrane component of the OleC ABC transporter involved in oleandomycin resistance in Streptomyces antibioticus; Olano C et al.; The OleC ABC transporter of Streptomyces antibioticus is constituted by an ATP-binding protein (OleC) and a hydrophobic protein (OleC5) . Here we present experimental evidence demonstrating that the OleC5 protein is an integral membrane protein and we propose a topological model for its integration into the membrane . This model is based on the generation of hybrid proteins between different regions of OleC5 and a Escherichia coli beta-lactamase (BlaM) and the determination of the minimal inhibitory concentrations to ampicillin in these constructions . Fusions were generated both by cloning specific fragments of oleC5 and by creating ExoIII nested deletions of the gene . In the topological model proposed there will be six alpha-helix transmembrane regions, two cytoplasmic and four periplasmic loops and a hydrophobic linker domain.

Biochemistry, 1996 Sep 24, 35(38), 12338 - 46
RNA molecules that specifically and stoichiometrically bind aminoglycoside antibiotics with high affinities; Wang Y et al.; RNA aptamers had previously been selected which were able to bind to the aminoglycoside antibiotic tobramycin with high affinity (Wang & Rando, 1995) . Consensus sequences are found in a variety of constructs, and these sequences were mapped to stem-loop regions by Mfold secondary structure prediction . A tobramycin-based affinity cleavage reagent specifically cleaves the aptamers in their consensus regions . A fluorescence depolarization method is developed to accurately measure the affinity and stoichiometry of aminoglycoside binding to RNA constructs . An RNA aptamer (J6RNA) selected to bind to the aminoglycoside antibiotic tobramycin is shown to do so with an affinity of 0.77 nM and a stoichiometry of 1:1 . (Fluorescently labeled) 5-carboxytetramethylrhodamine tobramycin (CRT) is used as a ligand in the fluorescence depolarization studies . J6RNA binding is quite specific for tobramycin, and weakly binds structurally related aminoglycosides with affinities 10(3)-10(4)-fold lower than that for tobramycin . Specific aminoglycoside binding aptamers of this type should be useful for revealing the rules of RNA-aminoglycoside recognition.

Mol Cell Biochem, 1996 Sep 6, 162(1), 75 - 82
Effect of anthracycline antitumor antibiotics (adriamycin and nogalamycin) and cycloheximide on the biosynthesis and processing of major UsnRNAs; Ray R et al.; In the present study, anthracycline antitumor antibiotics (e.g . adriamycin and nogalamycin), the potent RNA synthesis inhibitors and cycloheximide, the protein synthesis inhibitor, have been used to understand the events of biosynthesis and processing of major UsnRNAs (U1-U6) . The anthracyclines inhibit the UsnRNAs biosynthesis (in terms of labelling) differentially in a dose dependent manner . The inhibitory effect of adriamycin and nogalamycin reached plateau at a concentration of 2.5 micrograms/ 10(6) cells/ml and 0.1 microgram/10(6) cells/ml respectively and indicates that nogalamycin is more inhibitory than adriamycin . The inhibition of the UsnRNAs synthesis (in terms of labelling) became maximum within 30 min of incubation and remained unaltered even after 2 h . Thus, it shows that the anthracyclines preferentially inhibit the initiation of the UsnRNA genes' transcription as it has been seen in cases of other large RNAs' synthesis by some other laboratories . The higher inhibitory effect of the anthracyclines on the biosynthesis of U5 and U6 compared to other UsnRNAs indicates the presence of more binding sites on the U5 and U6 snRNA genes . In presence of the anthracyclines, there was high retention of cytoplasmic major pre-UsnRNAs/ UsnRNAs which indicates that the elongation of the UsnRNA synthesis is probably impaired along with initiation; because for the proper processing of the pre-UsnRNAs, formation of the correct secondary structure of that pre-UsnRNA is necessary . Cycloheximide showed some differential effect on the pol II transcribed UsnRNAs (U1-U5) biosynthesis (in terms of labelling) however it has no effect on the pol III transcribed U6 snRNA . It implies that in the pol II transcribed UsnRNAs, some transacting labile factors, either activator or inhibitor, are involved . Whereas, the processing of the UsnRNAs (either pol II or pol III transcribed) was affected more or less in a similar fashion in presence of cycloheximide, indicating the involvement of some transacting labile factors in this event.

Pharm Pract Manag Q, 1996 Oct, 16(3), 11 - 8
Formulary management: antibiotics and therapeutic interchange; Massoomi F; A well-managed formulary provides pharmacy managers with opportunities for decreasing drug expenditures . Therapeutic interchange constitutes one of the many programs under a formulary system which may yield cost savings as improved patient outcomes . The process of therapeutic interchange is described and compared with therapeutic substitution and generic substitution . A procedure for developing and implementing a therapeutic interchange program is presented with case studies.

Proc Natl Acad Sci U S A, 1996 Sep 3, 93(18), 9420 - 4
The structure of bovine F1-ATPase complexed with the peptide antibiotic efrapeptin; Abrahams JP et al.; In the previously determined structure of mitochondrial F1-ATPase determined with crystals grown in the presence of adenylyl-imidodiphosphate (AMP-PNP) and ADP, the three catalytic beta-subunits have different conformations and nucleotide occupancies . AMP-PNP and ADP are bound to subunits beta TP and beta DP, respectively, and the third beta-subunit (beta E) has no bound nucleotide . The efrapeptins are a closely related family of modified linear peptides containing 15 amino acids that inhibit both ATP synthesis and hydrolysis by binding to the F1 catalytic domain of F1F0-ATP synthase . In crystals of F1-ATPase grown in the presence of both nucleotides and inhibitor, efrapeptin is bound to a unique site in the central cavity of the enzyme . Its binding is associated with small structural changes in side chains of F1-ATPase around the binding pocket . Efrapeptin makes hydrophobic contacts with the alpha-helical structure in the gamma-subunit, which traverses the cavity, and with subunit beta E and the two adjacent alpha-subunits . Two intermolecular hydrogen bonds could also form . Intramolecular hydrogen bonds probably help to stabilize efrapeptin's two domains (residues 1-6 and 9-15, respectively), which are connected by a flexible region (beta Ala-7 and Gly-8) . Efrapeptin appears to inhibit F1-ATPase by blocking the conversion of subunit beta E to a nucleotide binding conformation, as would be required by an enzyme mechanism involving cyclic interconversion of catalytic sites.

Compend Contin Educ Dent, 1996 Sep, 17(9), 871 - 2, 875-82; quiz 884
Using pulsatile pressure saline/antibiotic irrigation before reduction and fixation of infected mandibular fractures: literature review and report of two cases; Betts NJ et al.; The efficacy of pulsatile pressure saline irrigation has been demonstrated in the orthopedic, surgical, and dental literature . However, its use for treating infected mandibular fractures has not been documented . This article reviews the literature concerning pressure irrigation . The pulsatile pressure saline/antibiotic irrigation technique and indications for its use during the treatment of infected mandibular fractures are demonstrated with two case reports . The pulsatile pressure saline/antibiotic irrigation system is a useful adjunct to the standard therapeutic modalities of infection management . It is also useful for managing infected mandibular fractures, especially when open reduction and internal fixation with bone plates have been planned.

Leuk Lymphoma, 1996 Sep, 23(1-2), 159 - 63
Stepdown single agent antibiotic therapy for the management of the high risk neutropenic adult with hematologic malignancies; Horowitz HW et al.; The standard of therapy for the high risk adult neutropenic host being treated with broad spectrum antibiotics for fever has been to continue intravenous antibiotics until neutropenia resolves . We performed a small, limited pilot study to determine if it is safe to switch these patients to oral monotherapy with ciprofloxacin . Ten patients with hematologic malignancies who had < or = 108 granulocytes/mm3 after cytoreductive therapy and were afebrile for at least five days had intravenous antibiotics discontinued and were placed on oral ciprofloxacin . Eight patients were able to be discharged from the hospital and seven were treated without the need for reinstitution of intravenous therapy . Of the three failures, one developed fever with a new bloodstream infection and two developed fever with relapse of leukemia . Patients remained on ciprofloxacin an average of 14.5 days (range 4 to 35 days) . Aggregate cost savings for the 10 patients from this approach were estimated to be $11,400 for antibiotics and $88,800 for hospitalization . If corroborated in larger, randomized studies, the use of "stepdown monotherapy" may be a cost effective approach to the management of the stable neutropenic patient.

Radiats Biol Radioecol, 1996 Sep-Oct, 36(5), 727 - 30
{Effects of a synthetic carbon-mineral sorbent and antibiotics on the development of combined radiation and thermal injury}; Nesterenko VS et al.; Male Wistar rats exposed to whole-body irradiation, the midline absorbed dose was 7.5 Gy . Full-sickness thermal burn 15% of body surface inflicted immediately after irradiation . Experimental study of the therapeutic efficacy of enterosorption alone or in combination with antibiotics doxycycline and ciprofloxacin performed . The strong decrease of bacterial endotoxemia, toxic oligopeptides' level and general blood toxicity revealed after treatment compared with non-treated animals with combined injuries . Corrections of postirradiation intestinal dysbacteriosis revealed too . The best result observed when carbon mineral sorbent and antibiotics administered daily within the first 10-14 days after combined injury . Survival of treated animals increased up to 80% (all rats of control group died during 30 days after combined injury).

Oreg Nurse, 1996 Sep, 61(3), 4 - 5
Do antibiotics decrease effectiveness of oral contraceptives?
Cottet C.
PIP: The number of accidental pregnancies occurring in oral contraceptive (OC) users who are concurrently taking certain antibiotics and antifungal agents exceeds the 1% failure rate associated with OCs, suggesting some form of drug interaction . Two mechanisms of action have been proposed to explain this phenomenon . First, drugs such as rifampin and griseofulvin induce liver enzymes that break down the estrogen and progestin contained in OCs, reducing plasma hormone levels . Second, changes in the intestinal bacterial flora induced by penicillin and tetracycline may reduce the gut's absorption of hormones, also compromising efficacy . Since rifampin and griseofulvin are the medications most frequently implicated in accidental pregnancies in OC users, the induction of liver enzymes is the more probable, potent cause of failure . Although the risk of pregnancy due to OC-antibiotic interactions is extremely small, OC users prescribed antibiotics should be warned to use condoms or spermicides until the antibiotics are discontinued .

Intensive Care Med, 1996 Sep, 22(9), 981 - 4
Short-term impact of the European Consensus Conference on the use of selective decontamination of the digestive tract with antibiotics in ICU patients; Misset B et al.; Because it remained controversial, the use of selective digestive decontamination (SDD) in patients in the intensive care unit (ICU) was chosen as the topic of the first European Consensus Conference in Intensive Care Medicine (ECCICM) in December, 1991 . The Consensus Bureau decided to assess the impact of this conference 2 years afterwards . For this purpose, a questionnaire was sent to the members of the European Society of Intensive Care Medicine, the Societe de Reanimation de Langue Francaise and the Societe Francaise d'Anesthesie et Reanimation before the conference . The recommendations following the conference discouraged the systematic use of SDD in ventilated patients and urged the monitoring of bacterial resistance and adapting antibiotics to epidemiology of the units . Two years after the conference, the same questionnaire was sent to those physicians who had responded to the first one . Eighteen percent used SDD for all ventilated patients and 17% remain users after 2 years . Among the occasional (32%) or continual (17%) users of SDD, the regimens used were mostly intravenous cefotaxime (60% of systemic antibiotics) and a topical combination of polymixin E, tobramycin, and amphotericin B (62% of overall topical combinations) . The antibiotics used were unchanged after 2 years in almost all cases . In conclusion, the short-term impact of the Consensus Conference on SDD in ICU patients has been poor . This may be related to the continuing insufficiency of strong, definite data regarding the impact of this technique upon mortality and the theoretical risk of resistance to antibiotics, thus allowing physicians to stick to their policies until there is new evidence.

Indian J Med Res, 1996 Sep, 104, 216 - 22
Spasmogenic action of beta-lactam antibiotics on the gastrointestinal tract of experimental animals; Jankovic SM et al.; We have investigated the effects of beta-lactam antibiotics on isolated preparations of rat fundus, ileum, and the body of feline stomach . Isotonic changes of isolated preparations were recorded . Benzylpenicillin (EC50 = 1.31 +/- 0.13 x 10(-5) M), ampicillin (EC50 = 2.16 +/- 0.15 x 10(-5) M), cefotaxime (EC50 = 1.33 +/- 0.15 x 10(-5) M), ceftriaxone (EC50 = 4.39 +/- 0.13 x 10(-5) M) and ceftazidime (EC50 = 1.42 +/- 0.01 x 10(-3) M) produced concentration-dependent tonic contractions of rat fundus . Rat ileum and feline stomach did not respond on these substances . Lidocaine (2.3 x 10(-5) M) and physostigmine (1.0 x 10(-8) M) significantly potentiated contractions produced by benzylpenicillin . On the other hand, methysergide (1.4 x 10(-7) M) and atropine (9.6 x 10(-9) M) significantly blocked tonic contractions produced by benzylpenicillin . Effects of beta-lactam antibiotics on smooth muscle isolated preparations were tissue and species dependent, indicating selectivity of their action.

J Antimicrob Chemother, 1996 Sep, 38(3), 465 - 73
Cytotoxicity of macrolide antibiotics in a cultured human liver cell line; Viluksela M et al.; Cytotoxicity of erythromycin base, erythromycin estolate, erythromycin-11,12-cyclic carbonate, roxithromycin, clarithromycin and azithromycin was compared in cultured human non-malignant Chang liver cells using reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide and cellular protein concentration as end points of toxicity . Erythromycin estolate was the most toxic macrolide in all tests differing clearly from all the other macrolides studied . Erythromycin-11,12-cyclic carbonate was also more toxic than the other macrolides . Roxithromycin and clarithromycin were the next toxic derivatives, while erythromycin base and azithromycin were least toxic . Thus, cytotoxicity of the new semisynthetic macrolides, roxithromycin, clarithromycin and azithromycin, is not substantially different from that of erythromycin base . In view of the low level of hepatotoxicity of macrolides hitherto reported in humans, the results do not suggest any substantial risk for hepatic disorders related to the use of azithromycin, clarithromycin and roxithromycin.

Mol Microbiol, 1996 Sep, 21(5), 1075 - 85
The cutRS signal transduction system of Streptomyces lividans represses the biosynthesis of the polyketide antibiotic actinorhodin; Chang HM et al.; The nucleotide sequence of a two-component signal transduction operon (cutRS) of Streptomyces lividans TK64 was elucidated . Transcription of the operon was detected during the transition and stationary phases of growth, initiating at a single site upstream of cutR . This promoter region also possessed promoter activity directed away from cutRS, which appears to be responsible for the previously observed suppression of the translational deficiency of a melC1 mutation . Mutations in cutR and cutS were generated by gene replacement . The resulting mutants exhibited accelerated and increased production of the polyketide antibiotic, actinorhodin, which could be reversed by introduction of cutR on a plasmid . cutRS was also shown to repress actinorhodin production in the closely related species, Streptomyces coelicolor A3(2) . The cutRS operon is the second two-component system found in Streptomyces that negatively regulates secondary metabolism.

Heart, 1996 Sep, 76(3), 289 - 90
Temporary decrease in heart rate in Lyme carditis during treatment with antibiotics; Dam EP et al.; Lyme disease is a recognised cause of atrioventricular block . In most cases the conduction disturbances are reversed by treatment with antibiotics . A 44 year old man with third degree atrioventricular block in Lyme carditis had a temporary decrease in heart rate during resolution of the heart block two days after treatment with antibiotics was started.

Biomaterials, 1996 Sep, 17(17), 1733 - 8
Comparative investigation of drug delivery of collagen implants saturated in antibiotic solutions and a sponge containing gentamicin; Wachol-Drewek Z et al.; Collagen implants of various structures and a gelatine sponge were placed in five different antibiotic solutions until complete saturation occurred . The antibiotics were chosen to represent different drug classes (gentamicin sulphate, cefotaxim, fusidic acid, clindamycin, vancomycin) . The collagen implants saturated with antibiotic solution and a lyophilized collagen sponge containing gentamicin sulphate were eluated in 0.066 M phosphate buffer (pH = 7.4) at 37 degrees C . The total eluation period is 7 d with buffer changes every 24 h . The antibiotic delivery by the collagen implants and the lyophilized sponge containing gentamicin sulphate is complete after a maximum of 4 d . If an implant that has a protective effect against wound infections over a period of 24-48 h is required, the materials described here are suitable . However, where treatment in infected areas should ensure antibiotic cover for 5-10 d, neither collagen materials immersed in antibiotic solutions nor collagen sponges containing gentamicin are suitable.

Biochemistry, 1996 Aug 20, 35(33), 10828 - 36
Interaction of the periplasmic dG-selective Streptomyces antibioticus nuclease with oligodeoxynucleotide substrates; Cal S et al.; The interaction of a periplasmic nuclease, isolated from Streptomyces antibioticus, with several oligodeoxynucleotide substrates has been studied . Double-stranded oligonucleotides that contain sequences of four or more consecutive deoxyguanosine residues are preferentially hydrolyzed, with the strongest cutting site occurring at GGG decreases G . The enzyme does not hydrolyze these sequences in single-stranded DNA . However the sequence selectivity of the nuclease is far from absolute . Other sequences can also be cut, albeit more poorly, and differences in cutting rates are observed for runs of dG bases that differ in their flanking sequences . An oligonucleotide, thirty-six bases in length, that contains a central run of five dG bases has been used to evaluate the importance of the individual deoxyguanosines in recognition and cleavage . With this oligonucleotide cutting takes place at GG{symbol: see text}G decreases G{symbol: see text}G (decreases, most prominent cut; {symbol: see text}, less prominent cuts) . The use of dG base analogues revealed that two bases, one and two steps removed from the cleavage site in the 5' direction (*G*GG decreases), were of most importance in the determination of the nuclease DNA cleavage selectivity . Of these the inner starred dG was the most critical . The use of 5-methyldeoxycytidine also showed that the dC, base paired to this critical dG, influenced cleavage specificity . The overall pattern of results seen with the base analogues suggested that the nuclease interacted with both strands of the DNA and also contacted the nucleic acid in both the major and minor grooves . Gel retardation analysis together with footprinting experiments using hydroxyl radicals, dimethyl sulfate, and ethylnitrosourea indicated that the nuclease does not form a tight and specific complex with sequences containing dG runs, at least in the absence of the essential co-factor, Mg2+.

FEBS Lett, 1996 Aug 19, 392(1), 25 - 9
Immunolocalization and pharmacological relevance of oligopeptide transporter PepT1 in intestinal absorption of beta-lactam antibiotics; Sai Y et al.; A polyclonal antibody (anti-PepT1/C) was raised against the rabbit intestinal H(+)-coupled oligopeptide transporter, PepT1 . Anti-PepT1/C detected 70-80-kDa protein in crude membranes obtained from rabbit duodenum, jejunum and ileum . PepT1 was localized in the brush-border of the absorptive epithelial cells by subcellular fractionation of membranes on a sucrose density gradient and by immunohistochemistry using light and electron microscopy . Transport activity for cephalosporins and dipeptide expressed in Xenopus laevis oocytes injected with total mRNA obtained from rabbit small intestine was eliminated completely by prehybridization of the mRNA with antisense oligonucleotide against the 5'-coding region of rabbit PepT1 cDNA.

Arzneimittelforschung, 1996 Aug, 46(8), 815 - 21
Mutagenicity study of the new cephalosporin antibiotic cefditoren pivoxil; Shindo Y et al.; The mutagenicity of a cephalosporin antibiotic, (-)-(6R,7R)-2,2-dimethylpropionyloxymethyl 7-{(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido}-3-{(Z)-2- (4-methylthiazol-5-yl) ethenyl}-8-oxo-5-thia-1-azabicyclo{4.2.0}oct-2-ene-2-carboxylate (cefditoren pivoxil, CAS 117467-28-4, CDTR-PI), was evaluated by various mutagenicity tests as follows: the reverse mutation assay in bacteria, the chromosomal aberration test with Chinese hamster CHL cells, the micronucleus test with mice, the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus gene mutation test with L5178Y cells, the chromosomal aberration test with human lymphocytes, the unscheduled DNA synthesis test with rat stomach mucosa cells, and the cell transformation test with BALB/3T3 cells . CDTR-PI induced the structural chromosomal aberrations considered direct action in the chromosomal aberration test with CHL cells at concentrations of 150 micrograms/ml and more, but in none of the other mutagenicity tests even in excessive doses . Evaluation for clastogenicity with metabolites of CDTR-PI and checking for formaldehyde generation in the culture medium appeared to verify that the original source of the clastogenicity of this antibiotic was a formaldehyde generated from a pivoxil radical of CDTR-PI . The carcinogenicity of formaldehyde has been reported as negative in rats administered orally for 2 years . These results suggested the CDTR-PI would reveal neither mutagenicity nor carcinogenicity under clinical conditions.

Fundam Appl Toxicol, 1996 Aug, 32(2), 205 - 16
In vitro and in vivo ultrastructural changes induced by macrolide antibiotic LY281389; Horn JW et al.; High doses of LY281389 (9-N-(n-propyl)-erythromycylamine) cause cytoplasmic vacuolar changes in striated and smooth muscle characteristic of drug-induced phospholipidosis . This study characterized phospholipidosis in striated and smooth muscle of rats and dogs, compared in vivo observations with those in a cultured rat myoblast model, and attempted to confirm the lysosomal origin of the drug-induced vacuoles . Standard transmission electron microscopy and acid phosphatase cytochemistry techniques were used to evaluate ultrastructural changes in vivo and in vitro . Rats and dogs exposed to LY281389 had a time- and dose-related increase in number and size of vacuoles containing concentric lamellar figures in cardiac and skeletal muscle . Cytochemical staining of dog stomach smooth muscle for acid phosphatase, a lysosomal enzyme, stained the periphery of vacuoles that contained concentric lamellar figures . Cultured rat L6 myoblast cells were exposed to 0.25 mg LY281389/ml for 2.5, 5, 10, 20, 30, or 90 min and 2, 6, 12, 24, or 48 hr . Cell cultures exposed for 2 hr had several predominantly large, clear, membrane-bound vacuoles, and at 6 and 12 hr there were greater numbers of large vacuoles that contained increased amounts of membranous figures . Following 24- or 48-hr exposures, vacuoles occupied most of the cytoplasmic volume, and were engorged predominantly with amorphous or granular material . These findings indicate that LY281389 can induce similar phospholipidosis-like vacuolar changes in rat and dog muscle and in a cultured rat muscle cell line . Further, positive acid phosphatase staining of drug-induced vacuolar structures, in conjunction with standard transmission electron microscopy techniques, strongly suggests that vacuoles seen in vitro and in vivo are lysosomal in origin.

Clin Transplant, 1996 Aug, 10(4), 386 - 8
Prophylactic wound antibiotics for combined kidney and pancreas transplants; Barone GW et al.; For combined kidney and pancreas transplant recipients infectious complications remain a major source of morbidity . With as many antibiotic protocols as transplant centers, the exact type and duration for prophylactic wound antibiotics remains undefined . A retrospective review of our series of 40 combined kidney and pancreas transplants was performed using a single 1 g dose of cefazolin preoperatively along with cefazolin bladder and intra-abdominal irrigation . Two patients developed superficial wound infections for a rate of 5% (2/37) . The deep wound infection rate was 11% (4/37), and all followed either a bladder anastomotic leak or the initial development of transplant pancreatitis . Our overall rate of 16% is very comparable with other series of combined kidney and pancreas transplant recipients . To help eliminate the potential development of superinfections and resistant organisms, a single dose of antibiotics appears to be as effective for wound prophylaxis in these patients when compared to multiple-antibiotic and multiple-day regiments . A randomized prospective study of prophylactic antibiotics in combined kidney and pancreas transplants is needed.

Eur Respir J, 1996 Aug, 9(8), 1590 - 5
Initial antibiotic therapy for lower respiratory tract infection in the community: a European survey; Huchon GJ et al.; A survey of first-line antibiotic prescription in community-acquired lower respiratory tract infection (LRTI) by general practitioners (GP) was carried out simultaneously, using the same methodology in France, Germany, Italy, Spain and the UK . Data were obtained from 2,056 patients and 605 GPs . There was no antibiotic prescription in 17% of all LRTIs and 13% of community-acquired pneumonia (CAP) in the five countries taken together; and in 32% of all LRTIs and in 23% of CAP in Germany . Of patients with acute bronchitis, exacerbation of chronic bronchitis and viral lower respiratory tract infection, 87, 92 and 71% received antibiotics, respectively . The most frequent prescriptions were penicillins in France and the UK, third-generation cephalosporin in Italy, tetracycline in Germany and macrolide in Spain . The daily dosage of aminopenicillin prescribed was: 41% <1.5 g; 49% > or = 1.5 g and <3 g; and 10% > or = 3 g . In Italy, 53% of all antibiotics were injected in all LRTIs, and 71% in CAP; in contrast, antibiotic injection was lower than 2% both in the UK and Germany, with an average of 14% in the five countries combined . We conclude that there are variations in antibiotic prescription by GPs in Western Europe; differences are likely to be multifactorial, but could, in part, be explained by differences in health systems and sources of information available to GPs.

J Periodontol, 1996 Aug, 67(8), 831 - 8
Systemic antibiotics in periodontics; Partial Achilles tendon ruptures associated with fluoroquinolone antibiotics: a case report and literature review; Department of Orthopaedic Surgery, Baylor College of Medicine, Houston, Texas, USAFluoroquinolone antibiotics (such as olprofloxacin, pefloxacin, ofloxacin, norfloxacin, temafloxacin, etc.) have recently been implicated in the etiology of Achilles tendinitis and subsequent tendon rupture . We report on a patient with bilateral partial Achilles tendon ruptures associated with ciprofloxacin therapy and present a review of the current literature on this increasingly recognized complication . Treatment with fluoroquinolones should be discontinued at the first sign of tendon inflammation so as to reduce the risk of subsequent rupture . Magnetic resonance imaging is useful in distinguishing between Achilles tendinitis and partial tendon rupture.

New Horiz, 1996 Aug, 4(3), 345 - 52
Could invasive diagnostic techniques for ventilator-associated pneumonia be associated with reduced antibiotic usage in the ICU?
Brun-Buisson C.
ICUs are often viewed as the epicenter of bacterial resistance . Overuse of antibiotics is one factor associated with this characteristic; other such factors include overcrowding, suboptimal observance of hygienic practices, cross-transmission of resistant strains, and high susceptibility of patients housed in ICUs . Evidence is scarce that different approaches to diagnosing infections, especially of the lower respiratory tract, can influence overall patterns of antibiotic usage and resistance . However, it is likely that more antibiotics are being administered to patients with suspected respiratory tract infections when diagnosed using nonspecific techniques than when more specific techniques are being used routinely . Additionally, the evidence is mounting that prior antibiotic usage is associated with increased risk of lower respiratory tract infection (LRTI), and also of infection caused by high-risk antibiotic-resistant pathogens, which in turn are associated with higher risk of treatment failure and mortality than their susceptible counterparts . A logical approach that may partially resolve this problem is to use specific diagnostic techniques, which will result in avoiding overtreating patients with suspected LRTI.

Aliment Pharmacol Ther, 1996 Aug, 10(4), 623 - 30
The safety and efficacy of ranitidine bismuth citrate in combination with antibiotics for the eradication of Helicobacter pylori; Wyeth JW et al.; BACKGROUND: Ranitidine bismuth citrate is a novel salt of ranitidine and a bismuth citrate complex . It has intrinsic antisecretory and anti-Helicobacter pylori activity, but monotherapy rarely eradicates H . pylori infection in man . AIM: A pilot study to investigate rates of H . pylori eradication achieved by co-prescription of ranitidine bismuth citrate with antibiotics, and to identify several regimens which would merit further investigation . METHOD: One hundred dyspeptic patients infected with H . pylori were randomly allocated to treatment with ranitidine bismuth citrate 800 mg b.d . plus either amoxycillin, metronidazole, clarithromycin, cefuroxime axetil, tetracycline, tetracycline plus metronidazole or clarithromycin plus tetracycline for 14 days . Eradication of infection was assessed using the 13C-urea breath test 4 weeks after the end of treatment . RESULTS: In a per protocol analysis eradication of H . pylori ranged between 22 and 100%; the intention-to-treat eradication rates ranged between 15 and 92% . No adverse events were specifically attributed to ranitidine bismuth citrate . CONCLUSION: Co-prescription therapy, using ranitidine bismuth citrate and one or more antibiotics, is suitable for further investigation in large-scale clinical trials in patients infected with H . pylori.

CRNA, 1996 Aug, 7(3), 118 - 25
Allergic reaction to antibiotics during anesthesia: a case report; Flaherty SA; The increased number of drugs used in anesthetic practice today as well as cross-sensitivity between drugs, have lead to a higher risk of allergic responses . This article describes the evolution and treatment of an allergic reaction, discusses the classification of allergic responses, and details the treatment of anaphylactic/anaphylactoid reactions . The allergic potential of drugs commonly used in the administration of anesthesia is highlighted.

Pancreas, 1996 Aug, 13(2), 198 - 201
Prophylactic antibiotics in treatment of severe acute alcoholic pancreatitis; Delcenserie R et al.; Infectious complications currently account for 80% of deaths from acute pancreatitis . The aim of this study was to evaluate the necessity for prophylactic antibiotics in patients with severe acute pancreatitis . Twenty-three consecutive patients suffering from acute alcoholic pancreatitis with computed tomography demonstrating two or more fluid collections were randomly assigned to one of two groups receiving either nonantibiotic treatment or prophylactic antibiotics (ceftazidime, amikacine, and metronidazole for 10 days) . Sepsis was always diagnosed by positive cultures . Seven episodes of severe sepsis occurred (pancreatic infection and septic shock) in the nonantibiotic group, and no infection occurred in the prophylactic antibiotic group (p < 0.03) . In conclusion, the use of prophylactic antibiotics in severe alcoholic acute pancreatitis significantly reduces the incidence of severe infection.

Pancreas, 1996 Aug, 13(2), 184 - 92
Therapeutic effects of continuous intraarterial antibiotic infusion in preventing pancreatic infection in experimental acute necrotizing pancreatitis; Hayashi J et al.; To determine the efficacy of antibiotics in the prevention of pancreatic infection and the process of aggravation after induction of acute pancreatitis, antibiotic was administrated intravenously or intraarterially, starting 6 h after acute pancreatitis was induced in dogs by injecting autologous gallbladder bile into the main pancreatic duct . Flomoxef, recognized as an antibiotic able to penetrate well into pancreas tissue, was selected for the present study . Animals were divided into three groups: no antibiotic given (Group A), antibiotic given intravenously as a bolus injection of 25 mg/kg every 6 h (Group B), and antibiotic infused continuously into the celiac trunk (4 mg/kg/h) (Group C) . Compared with Group A, continuous intraarterial infusion of antibiotic (Group C) significantly improved the survival rate and decreased the serum levels of phospholipase A2(PLA2) activity and endotoxin . Furthermore, it completely prevented the occurrence of pancreatic infection, not only ameliorating the severity of pancreatic necrosis but also reducing the activity levels of amidase, trypsin-like enzyme, and PLA2 in pancreas tissue . Group B showed little beneficial effect . Antibiotic concentration in peripheral blood and pancreas tissue was significantly higher in Group C than in Group B . These results suggest that continuous arterial infusion of antibiotics into the feeding artery of the pancreas is an effective modality for preventing pancreatic infection and aggravation of severe acute pancreatitis.

Ear Nose Throat J, 1996 Aug, 75(8), 524 - 6, 528
Use of antibiotics for expansion of the Merocel packing following endoscopic sinus surgery; Shikani AH; Sinus packs that are used for hemostasis and the prevention of synechiae following endoscopic sinus surgery frequently get colonized with bacteria from the infected sinus, which increases the risk for infection . This study was conducted in an attempt to characterize the bacterial flora of the chronically infected sinus, and to evaluate whether direct installation of antibiotics into the sponge inhibits bacterial growth . Bacteria were cultured from 89% of the sinuses at surgery, and in 67% of the cases, the same bacteria were recovered from the sinus dressings one week later . When the Merocel sinus dressing was expanded with a combination of polymyxin, neomycin and hydrocortisone at the time of surgery, a 36% decrease in bacterial growth was observed, along with a decrease in the severity of pain associated with removal of the pack . This supports the concept of using an antibiotic for the expansion of the sponge following endoscopic sinus surgery.

J Okla State Med Assoc, 1996 Aug, 89(8), 267 - 74
Antibiotics and respiratory infections: do antibiotic prescriptions improve outcomes?
Hamm RM, Hicks RJ, Bemben DA.
BACKGROUND AND OBJECTIVES: Antibiotics are frequently prescribed for respiratory infections though most of these infections are viral . To determine whether this practice contributes to patient health and patient satisfaction, we studied the effect of antibiotic prescriptions on outcomes at 7 to 10 days . We also studied the effect of antibiotic prescriptions upon the accuracy of patients' beliefs about viruses . METHODS: One hundred thirteen patients with a respiratory infection completed questionnaires before and after their visit with their primary care doctor . A phone interview was completed 7 to 10 days later . Questions elicited their expectations for antibiotics, their beliefs about the efficacy of antibiotics, and satisfaction with the doctor . The phone interview asked whether they felt better, whether they had returned to the doctor about the same illness, satisfaction, and whether they would expect antibiotics for the same disease in the future . The doctors provided information about their diagnosis and treatment . RESULTS: No correlation was found between prescription of antibiotics and patient satisfaction, feeling better, return physician visits, or phone calls . Receiving antibiotics increased the likelihood the patients would expect antibiotics the next time they had an upper respiratory infection and made them more likely to have an inaccurate belief, that antibiotics kill viruses . CONCLUSIONS: The study found no evidence that antibiotics improve patient outcome in upper respiratory infections by making patients feel better at 7 to 10 days . Nor did it find evidence that antibiotics help physicians by reducing return visits or increasing patient satisfaction . Doctors are invited to reconsider their policies for prescribing antibiotics for upper respiratory infection.

J Antibiot (Tokyo), 1996 Aug, 49(8), 811 - 4
YM-24074, a new peptide antibiotic . II . Structural elucidation; Sato T et al.; YM-24074 (formerly called YL-01869P) is a new antibiotic and type I collagenase inhibitor . The structure of this compound was elucidated by spectroscopic analysis and confirmed by acid degradation to be N-(1"-acetyl-3"-methylbutyl)-2- {2'-{(N-hydroxycarbamoyl)methyl}heptanoyl}-hexahydropyrid azine-3-carboxamide . The stereochemistry of two of three chiral centers was determined by degradation products to be 3S, 2'R.

J Antibiot (Tokyo), 1996 Aug, 49(8), 765 - 9
Kanchanamycins, new polyol macrolide antibiotics produced by Streptomyces olivaceus Tii 4018 . II . Structure elucidation; Stephan H et al.; Kanchanamycins are a new group of polyol macrolide antibiotics isolated from Streptomyces olivaceus Tu 4018 . They all share a common bicyclic carbon skeleton formed by a 36-membered lactone ring and a 6-membered hemiacetal ring . A feature unusual for that class of macrolides is the terminal urea moiety observed in kanchanamycin A . The structures of the kanchanamycins were determined by electrospray MS and modern 2D NMR techniques . Due to substantial overlap of the signals intensive use of inverse detected heteronuclear correlation experiments (HSQC, HMBC, 2D-HSQC-TOCSY) was made.

J Mass Spectrom, 1996 Aug, 31(8), 855 - 60
Application of fast atom bombardment combined with tandem mass spectrometry to the structural elucidation of O-demethylabierixin and related polyether antibiotics; Kim YH et al.; O-Demethylabierixin, a new polyether antibiotic, was isolated from a Streptomyces spp . Its structure elucidation was carried out with fast atom bombardment mass spectrometry (FAB-MS) and fast atom bombardment mass spectrometry-mass spectrometry (FAB-MS/MS) by comparing spectral patterns with those of structurally similar polyether compounds, nigericin and abierixin . The collision-induced dissociation (CID) of sodium-adduct and deprotonated molecular ions produced many cyclic ether rings-opened product ions via a series of the dissociative processes . Because of the negative charge of the carboxylate group at the end of the molecule, the charge-remote fragmentation pattern in the negative CID spectra of deprotonated molecular ions was very helpful for complete identification of product ions which are characteristic for cyclic ether structures . From this study, the new polyether antibiotic was identified to be O-demethylabierixin in which the methoxy group of six-membered ether ring in abierixin was replaced by the hydroxy group.

J Pharmacol Exp Ther, 1996 Aug, 278(2), 590 - 6
Comparative distribution of quinolone antibiotics in cerebrospinal fluid and brain in rats and dogs; Ooie T et al.; The distribution of the quinolone antibiotics, norfloxacin (NFLX), AM-1155, fleroxacin (FLRX), ofloxacin, sparfloxacin (SPFX) and pefloxacin (PFLX), in the central nervous system (CNS) was investigated in dogs and rats . In dogs, the steady-state cerebrospinal fluid (CSF) to unbound serum concentration ratio (Kp,uCSF) differed widely ranging from 0.11 (NFLX) to 1.0 (PFLX) . About a 10-fold difference between compounds was also observed in the Kp,uCSF in rats; however, these values were 25 to 50% smaller than those in dogs . Similarly, the brain to unbound serum concentration ratio (Kp,uBrain) of quinolones differed widely ranging from 0.15 (NFLX) to 1.5 (SPFX) in dogs and 0.04 (NFLX) to 0.33 (FLRX) in rats . The steady-state concentration ratio between CSF and brain tissue exhibited a 3-fold difference among quinolones (0.5 for PFLX to 1.6 for SPFX) in dogs, whereas, these values were all close to unity in rats . Kp,uBrain and Kp,uCSF all increased as the lipophilicity of the compound increased (except the Kp,uBrain in dogs) . We also found that the quinolones inhibited the saturable accumulation of {14C}FLRX (Km 660 microM) by the isolated rat choroid plexus . About a 20-fold difference among the apparent IC50 values for FLRX transport was observed between NFLX (6000 microM) and PFLX (300 microM) . The absence of a negative correlation between the affinity of the quinolones for this transport system, which in turn represents the efflux clearance from the CSF, and their in vivo distribution in rat CNS (Kp,uBrain or Kp,uCSF) suggests a minor contribution of this efflux system to the CNS distribution of quinolones.

FEMS Microbiol Lett, 1996 Aug 1, 141(2-3), 157 - 62
Characterization of the ATPase activity of the N-terminal nucleotide binding domain of an ABC transporter involved in oleandomycin secretion by Streptomyces antibioticus; Aparicio G et al.; The oleB gene of Streptomyces antibioticus, oleandomycin producer, encodes an ABC transporter containing two putative ATP-binding domains and is involved in oleandomycin resistance and secretion in this organism . We have overexpressed in Escherichia coli the N-terminal nucleotide-binding domain of OleB (OleB') as a fusion protein and purified the fusion protein by affinity chromatography . The fusion protein showed ATPase activity dependent on the presence of Mg2+ ions . ATPase activity was resistant to specific inhibitors of P-, F-, and V-type ATPase whereas sodium azide and 7-chloro-4-nitrobenzo-2-oxa-1,3-diazole (NBD-C1) were strong inhibitors . The change of Lys71, located within the Walker A motif of the OleB' protein, to Gln or Glu caused a loss of ATPase activity, whereas changing to Gly did not impair the activity . The results suggest that the intrinsic ATPase activity of purified fusion protein can be clearly distinguished from other ATP-hydrolysing enzymes, including ion-translocating ATPases or ABC-traffic ATPases, both on the basis of inhibition by different agents and since it hydrolyzes ATP without interacting with a hydrophobic membrane component.

Am J Obstet Gynecol, 1996 Aug, 175(2), 358 - 61; discussion 362
Use of a subcutaneous closed drainage system and antibiotics in obese gynecologic patients; Gallup DC et al.; OBJECTIVE: The purpose of this study was to evaluate the effect of subcutaneous closed drainage systems and prophylactic antibiotics on the wound breakdown rate in obese patients undergoing gynecologic surgery . STUDY DESIGN: A prospective study was performed on 197 obese patients who were randomly selected to have a subcutaneous drain . Incision closure technique was standardized . Antibiotic usage was not randomized . Demographic data, perioperative data, and postoperative complications were noted and analyzed by X2 test and 2 x 2 contingency tables . RESULTS: The overall complication rate was 25%, with 20% (22/109) among the group receiving a drain versus 31% (27/88) without a drain . Seventeen patients (8.6%) had wound breakdowns: 7 of 109 (6.4%) with drains and 10 of 88 (11.4%) without drains . Prophylactic antibiotics were given to 46% (50/109) in the drain group and 51% (45/88) without a drain . Fewer patients (2%) with a drain receiving antibiotics had wound breakdowns . The group with the most breakdowns had neither a drain nor antibiotics (14%) . CONCLUSION: We suggest the use of subcutaneous drains plus prophylactic antibiotics may decrease morbidity when operating on obese gynecologic patients.

Microbiology, 1996 Aug, 142 ( Pt 8), 1965 - 72
Production of hybrid anthracycline antibiotics by heterologous expression of Streptomyces nogalater nogalamycin biosynthesis genes; Ylihonko K et al.; A cluster of anthracycline biosynthetic genes isolated from Streptomyces nogalater was expressed in Streptomyces lividans and in Streptomyces galilaeus . A 12 kb DNA fragment cloned from this cluster in pIJ486 caused the production of a novel compound when introduced into S . lividans . The compound is derived from nogalonic acid methyl ester, an early intermediate in nogalamycin biosynthesis . Complementation with the cloned 12 kb fragment of S . galilaeus mutants blocked in aclacinomycin biosynthesis caused the production of hybrid anthracyclines . Cloning of the nogalamycin gene cluster should make possible a detailed study of the biosynthesis of this interesting antibiotic, as well as the production of novel anthracyclines of potential value as cytostatic drugs.

Biochem J, 1996 Aug 1, 317 ( Pt 3), 855 - 60
Antibiotic interactions with the hammerhead ribozyme:tetracyclines as a new class of hammerhead inhibitor; Murray JB et al.; A screening of a range of common laboratory antibiotics for inhibition of the hammerhead ribozyme has shown that in addition to certain aminoglycosides (most notably neomycin B) the tetracyclines are also effective inhibitors, with chlorotetracycline being more effective than tetracycline . Inhibition by chlorotetracycline is not as strong as that by neomycin B but is more complicated, with at least two binding sites apparent . As with hammerhead inhibition by neomycin B, chlorotetracycline inhibition can be overcome by raising the concentration of the Mg2+ ion cofactor . We find that around six Mg2+ ions will displace neomycin B, compared with twelve for chlorotetracycline . Inhibition observed in the presence of mixtures of neomycin B and chlorotetracycline is consistent with separate binding sites on the hammerhead for these two classes of antibiotic . Under certain conditions of the mixing order and low concentration of chlorotetracycline, enhancement of single-turnover hammerhead cleavage by up to 20% is observed, with higher concentrations of antibiotic being inhibitory . We have also found that the presence of 2.5% (v/v) DMSO causes a 30% enhancement of the single-turnover cleavage . These results thus extend the range of known inhibitors of hammerhead cleavage, and also demonstrate how the cleavage can be accelerated.

J Immunol, 1996 Aug 1, 157(3), 1071 - 9
Cross-reactivity of T cell lines and clones to beta-lactam antibiotics; Mauri-Hellweg D et al.; To clarify on a molecular level the specific T cell response to haptens like penicillin G, we generated T cell lines and clones from penicillin-allergic patients . Two types of beta-lactam reactivity of T cells could be delineated: one group of patients showed a rather restricted specificity, as the penicillin-elicited T cell lines generated from such donors proliferated only to the stimulating penicillin, but not to other beta-lactam antibiotics nor to cephalosporines, even if the side chain was identical . This indicates that the penicilloyl structure together with the side chain was recognized by these T cells . The second group comprised patients with more broadly reactive T cells, as they were restimulated by penicillin G as well as by related penicillins like amoxicillin or ampicillin, but not cephalosporines . This indicates that the penicilloyl structure, a common motif of penicillins, was important for T cell recognition . Clones generated from a broadly reactive patient confirmed this heterogeneity, as either monospecific or broadly specific T cell clones could be identified . This broad or very restricted pattern of T cell reactivity was reflected in the use of TCR Vbeta-chains: while the broadly reactive T cell lines showed a heterogenous TCR usage, the highly restricted T cell lines showed an up-regulation of one TCR Vbeta-chain . Thus, our data suggest that the outgrowth of T cells bearing a certain TCR Vbeta may be a sign of a limited cross-reactivity.

J Bone Joint Surg Am, 1996 Aug, 78(8), 1167 - 71
Comparison of intravenous and oral antibiotic therapy in the treatment of fractures caused by low-velocity gunshots . A prospective, randomized study of infection rates; Knapp TP et al.; One hundred and ninety consecutive patients (222 fractures) who had an extra-articular fracture of a long bone as a result of a low-velocity gunshot were randomized into two groups on the basis of the method of administration of antibiotics . Group 1 consisted of 101 patients (120 fractures) who were managed with intravenous administration of cephapirin sodium and gentamicin for three days . Group 2 comprised eighty-nine patients (102 fractures) who were managed with oral administration of ciprofloxacin for three days . The two groups were comparable in terms of the age of the patient, the locations of the fractures, and the time from the injury to the commencement of antibiotic therapy . Injuries that needed operative debridement or fixation were excluded . All patients were followed until the fracture had healed . Two infections developed in two of the ninety-nine patients (118 fractures) who completed the study in Group 1, and two infections developed in two of the eighty-seven patients (100 fractures) who completed the study in Group 2 . With the numbers available, there was no significant difference in the rates of infection (2 per cent for both) between the two groups . All four fractures that were complicated by infection were located in the distal half of the tibia . We concluded that oral and intravenous administration of antibiotics were equally effective for prophylaxis against infection after an extra-articular fracture from a low-velocity gunshot.

J Thorac Cardiovasc Surg, 1996 Aug, 112(2), 248 - 52
Rifampicin antibiotic impregnation of the St . Jude Medical mechanical valve sewing ring: a weapon against endocarditis; French BG et al.; The Dacron sewing ring material of the St . Jude Medical mechanical heart valve (St . Jude Medical, Inc., St . Paul, Minn.) was passively impregnated with rifampicin (60 mg/ml) both in its unsealed state and after sealing by the methods of preclotting in blood, autoclaving in blood, and autoclaving in 20% albumin . Antistaphylococcal activity in the Dacron material was assessed immediately after rifampicin impregnation and at regular periods up to 5 days after implantation into the goat aorta . When the Dacron material had been sealed by autoclaving in blood and autoclaving in 20% albumin significant retention of antistaphylococcal activity was found after 5 days in vivo . Best results were obtained with the use of autoclaved blood (p < 0.05) . We also compared these results with those obtained from impregnating commercially available gelatin-sealed (Gelseal) and collagen-sealed (Hemashield) Dacron material with rifampicin . Although antistaphylococcal activity was equivalent immediately after rifampicin impregnation, after 4 days in vivo the activity was negligible in Gelseal material (p < 0.05) and could not be demonstrated in Hemashield material . Rifampicin impregnation of the intact St . Jude Medical mechanical valve sewing ring may have an application in the prevention of prosthetic valve endocarditis and a clinical protocol is suggested.

Biochem Pharmacol, 1996 Jul 26, 52(2), 177 - 86
Engineered biosynthesis of peptide antibiotics; Stachelhaus T et al.; In certain bacteria and filamentous fungi, a wide variety of bioactive peptides are produced non-ribosomally on large protein templates, called peptide synthetases . Recently, significant progress has been made towards understanding the modular arrangement of these complex multifunctional enzymes and the mechanisms by which they generate their corresponding peptide products . It has now been established that the synthesis of bioactive peptides and the specification of their sequence are brought about by a protein template that contains the appropriate number and the correct order of activating units (domains) . These advances have enabled the development of a technique that permits the construction of hybrid genes encoding peptide synthetases with specifically altered substrate specificities . A programmed alteration within the primary structure of a peptide antibiotic is achieved by the substitution of an amino acid-activating domain in the corresponding protein template at the genetic level by a two-step recombination method . It utilizes successive gene disruption and reconstitution and demonstrates, for the first time, the potential of genetic engineering in the biosynthesis of novel peptide antibiotics . Many organisms, for instance those that cause diseases like tuberculosis and pneumonia, have evolved potent mechanisms of drug resistance . Therefore, the targeted engineering of peptide antibiotics could be one potential strategy for the development of novel drugs that overcome this resistance.

Biochemistry, 1996 Jul 23, 35(29), 9314 - 24
Structural characterization of the 1:1 adduct formed between the antitumor antibiotic hedamycin and the oligonucleotide duplex d(CACGTG)2 by 2D NMR spectroscopy; Pavlopoulos S et al.; 2D NMR spectroscopic methods have been used to determine the structure of the adduct formed between the antitumor antibiotic hedamycin and the oligodeoxyribonucleotide duplex d(CACGTG)2 . Evidence for both intercalation and alkylation in the adduct was observed, and a model for the binding interaction was constructed based on intermolecular NOEs and distance-restrained molecular dynamics . In our computationally refined model, the anthrapyrantrione chromophore of hedamycin is intercalated between the 5'-CG-3' bases with the two aminosugar groups placed in the minor groove and the six carbon bisepoxide side chain located in the major groove . The anglosamine sugar attached at C8 is oriented in the 3' direction relative to the intercalation site, while the N,N-dimethylvancosamine attached at C10 is oriented to the 5' side, with each aminosugar wedged between a guanine exocyclic amino group and one of the groove walls . The terminal epoxide carbon C18 is covalently bound to the N7 atom of the central guanine, as evidenced by lability of the C8 hydrogen of this purine upon reaction with hedamycin . Our binding model places the C10-attached N,N-dimethylvancosamine of hedamycin in van der Waals contact with the alkylated strand . A strong NOE contact verifies the close proximity of the terminal methyl group (C19) of the bisepoxide side chain to the methyl group of the thymine on the 3' side of the alkylated guanine . This, in conjunction with other data, suggests hydrophobic interactions between the bisepoxide chain and the floor of the major groove may contribute to sequence recognition . Furthermore, it is proposed that the 5'-CGT sequence selectivity of hedamycin arises, in part, from complementarity in shape between the chromophore substituents and the major and minor groove at the binding site.

Anal Chem, 1996 Jul 15, 68(14), 2426 - 31
Electrochemiluminescence-based detection of beta-lactam antibiotics and beta-lactamases; Liang P et al.; Bacterial resistance to clinically administered beta-lactam antibiotics is usually caused by beta-lactamases, enzymes that hydrolytically inactivate the antibiotics . This paper describes the use of electrogenerated chemiluminescence (ECL) to detect beta-lactam antibiotics and their hydrolysis by beta-lactamases . All 10 tested antibiotics were detected on the basis of their ability to participate in an ECL reaction with ruthenium(II) tris(bipyridine) . In every case, antibiotic-promoted ECL changed when the antibiotic was hydrolyzed by beta-lactamases or NaOH . Standard curves of antibiotic concentration versus ECL intensity showed that antibiotics could be quantitated to low micromolar concentrations . Substrate profiles were generated for four beta-lactamases using six structurally diverse beta-lactam antibiotics . ECL-based antibiotic detection was accomplished in untreated whole milk, and beta-lactamases were detected in crude bacterial broth culture . Because several structurally diverse antibiotics were detectable by ECL, this method may become valuable for the detection of many or all beta-lactam antibiotics and their inactivation by beta-lactamases.

Proc Natl Acad Sci U S A, 1996 Jul 9, 93(14), 6913 - 7
The structure of bovine F1-ATPase complexed with the antibiotic inhibitor aurovertin B; van Raaij MJ et al.; In the structure of bovine mitochondrial F1-ATPase that was previously determined with crystals grown in the presence of adenylyl-imidodiphosphate (AMP-PNP) and ADP, the three catalytic beta-subunits have different conformations and nucleotide occupancies . Adenylyl-imidodiphosphate is bound to one beta-subunit (betaTP), ADP is bound to the second (betaDP), and no nucleotide is bound to the third (betaE) . Here we show that the uncompetitive inhibitor aurovertin B binds to bovine F1 at two equivalent sites in betaTP and betaE, in a cleft between the nucleotide binding and C-terminal domains . In betaDP, the aurovertin B pocket is incomplete and is inaccessible to the inhibitor . The aurovertin B bound to betaTP interacts with alpha-Glu399 in the adjacent alphaTP subunit, whereas the aurovertin B bound to betaE is too distant from alphaE to make an equivalent interaction . Both sites encompass betaArg-412, which was shown by mutational studies to be involved in binding aurovertin . Except for minor changes around the aurovertin pockets, the structure of bovine F1-ATPase is the same as determined previously . Aurovertin B appears to act by preventing closure of the catalytic interfaces, which is essential for a catalytic mechanism involving cyclic interconversion of catalytic sites.

Chir Organi Mov, 1996 Jul-Sep, 81(3), 311 - 6
Specific antibiotic therapy by needle-aspiration for the treatment of osteomyelitis of the pubis . A description of two clinical cases; Corezzola R et al.; The authors describe two cases of osteomyelitis of the pubis, that exemplify the difficulty of differential diagnosis, as symptoms at the onset are "masked" by previous urologic pathologies (aspecific acute epididymitis and, respectively, urethritis cystica in the sequelae of radical prostatectomy) . The x-ray findings for osteolysis make a local biopsy necessary; the lesion may in fact, be mistaken for a neoplasm, particularly in patients who have previously been submitted to pelvic visceral surgery for the treatment of tumor . The needle-aspiration procedure and the execution of a cultural examination, in addition to a cytological one, provide unmistakeable data for diagnosis and treatment.

Biotechnol Prog, 1996 Jul-Aug, 12(4), 503 - 9
Mass transfer of antibiotics adsorbed by human serum albumin in hemodialyzers; Kanamori T et al.; The removal rate of a drug by a hemodialyzer is very important to determine the dosage of the drug to a patient without kidney function . Mass transfer of a drug in a hemodialyzer and a patient's body is more complicated than that of ordinary solutes because most drugs are adsorbed by serum albumin . In this paper, we reveal the adsorption characteristics of five clinical antibiotics onto human serum albumin (HSA) with new experimental methods and discuss the influence of adsorption characteristics on removal of antibiotics by hemodialyzers using mathematical models . The adsorption equilibrium of the antibiotics with HSA followed the Langmuir isotherm . Adsorption rates of the antibiotics onto HSA were measured using a constant-flow stirred tank reactor with an ultrafiltration module . A kinetic model for antibiotic transfer in a hemodialyzer and a patient's body was derived with the parameters obtained by the above experiments . Validity of the model was confirmed by dialysis experiments using hemodialyzers and antibiotic solutions including HSA . Removal estimation of a drug by hemodialysis therapy is feasible by the model with the parameters of the Langmuir isotherm for the drug.

Biopolymers, 1996 Jul, 39(1), 31 - 42
Crystallographic structure of a multiple beta-turn containing, glycine-rich heptapeptide: a synthetic precursor of the lipopeptaibol antibiotic trichodecenin I; Monaco V et al.; In continuation of our studies on the structure and function of peptaibol antibiotics, the conformational properties of a sequence analogous to that of Trichodecenin I (Z-Gly-Gly-D-Leu-Aib-Gly-D-Ile-D-Leu-OMe, where Z = benzyloxycarbonyl, Aib = alpha-aminoisobutyric acid, and OMe = methyl ester) have been investigated crystallographically . This sequence is the mirror image of the naturally occurring molecule and also of the C-terminal heptapeptide of the related lipopeptaibol Trichogin A IV (where, however, the Leu-OMe residue has replaced the original Leuol residue) . The molecule crystallized in the monoclinic system, space group P21, Z = 4, and cell parameters a = 11.610(5), b = 33.342(8), c = 11.735(4) A, beta = 110.42(1) degrees, V = 4257(3) A3 . The crystallographic refinement converges at residual values of R = 0.047 and wR2 = 0.134 on F2 . In the 1-5 segment the molecular conformation is virtually identical to that one reported from solution nmr studies of a similarly protected sequence {Biopolymers (1995), Vol . 35 . pp . 21-29)} and is characterized by beta-turns of type I at Gly1-Gly2, II' at Leu3-Aib4, and I at Aib4-Gly5 . In the crystal structure, a beta-sheet-like arrangement is seen at the C-terminus.

Clin Ther, 1996 Jul-Aug, 18(4), 716 - 25; discussion 702
The total process cost of parenteral antibiotic therapy: beyond drug acquisition cost; Hotchkies L et al.; Intravenous antibiotic therapy represents a considerable expense to hospital pharmacy budgets; however, when evaluating the cost of these therapies one needs to look beyond acquisition cost and consider the total "process" cost of treatment . These additional costs include the personnel time and the materials required for drug preparation and administration, maintenance of intravenous access, waste disposal, and therapeutic drug monitoring . This paper provides an examination of the daily process costs of intravenous therapy with cefazolin, cefotaxime, ceftazidime, once-daily ceftriaxone, cefuroxime, or aminoglycoside (tobramycin or gentamicin) combination therapy, where the aminoglycoside is given once daily or in divided doses . This analysis demonstrates that the costs associated with drug preparation and administration can equal or exceed drug acquisition costs and are highly dependent on dosing frequency . On this basis, ceftriaxone, at $52.21, is the least expensive of these antibiotic regimens in terms of total daily process cost, followed by the remaining cephalosporins at $53.29 to $94.57, aminoglycoside once-daily combinations at $93.44 to $99.65, and aminoglycoside multidose combinations at $103.26 to $111.42, respectively (values are given in constant 1995 Canadian dollars) . Once-daily ceftriaxone offers the potential for cost savings compared with other antibiotic regimens whose pharmacokinetics require multiple daily doses, due largely to the reduced resources required for ceftriaxone preparation and administration.

Infection, 1996 Jul-Aug, 24(4), 275 - 91
Immunomodulating effects of antibiotics: literature review; Van Vlem B et al.; Antibiotics can interact directly with the immune system . This is a review of the immunomodulating effects of antibiotics . The Medline database on CD-ROM was searched for the years 1987 to 1994 using the following search string: "thesaurus explode antibiotics/all AND (thesaurus explode immune-system/drug effects OR thesaurus immune-tolerance/drug effects)." Aspects of the immune system studied were aspects of phagocyte functions: phagocytosis and killing, and chemotaxis and aspects of lymphocyte functions: lymphocyte proliferation, cytokine production, antibody production, delayed hypersensitivity and natural killer-cell activity . In order to quantify and to compare immunomodulatory properties of antibiotics we calculated an "immune index," defined as: number of positive statements--number of negative statements/total number of statements . Concerning phagocytosis, positive effects were observed for cefodizime, imipenem, cefoxitin, amphotericin B and clindamycin and negative effects for erythromycin, roxithromycin, cefotaxime, tetracycline, ampicillin and gentamicin . Clindamycin, cefoxition and imipenem induce enhancement of chemotaxis, whereas cefotazime, rifampicin and teicoplanin decrease chemotaxis . Regarding lymphocyte proliferation, cefodizime has the strongest stimulating effect, whereas tetracycline has the strongest negative effect . Except for erythromycin and amphotericin B the number of statements reported is too small to be conclusive for the interpretation of effects on cytokine production . Erythromycin and amphotericin B appear to stimulate cytokine production . As to antibody production, cefodizime has the strongest positive effect, whereas josamycin, rifampicin and tetracycline have marked negative effects . For delayed hypersensitivity and the natural killer-cell activity the number of statements is too small for any single antibiotic to be conclusive . There are three markedly immuno-enhancing antibiotics (imipenem, cefodizime and clindamycin) and eight markedly immuno-depressing antibiotics (erythromycin, roxithromycin, cefotaxime, tetracycline, rifampicin, gentamicin, teicoplanin and ampicillin).

Mol Microbiol, 1996 Jul, 21(2), 385 - 96
afsR is a pleiotropic but conditionally required regulatory gene for antibiotic production in Streptomyces coelicolor A3(2); Floriano B et al.; The N-terminal region of AfsR, a putative pleiotropic regulatory protein for antibiotic production in Streptomyces coelicolor A3(2), is homologous to RedD and Actil-ORF4, pathway-specific regulatory proteins required for the production of the antibiotics undecylprodigiosin (Red) and actinorhodin (Act), respectively . The recent identification of afsS, which lies immediately 3' of afsR and which stimulates antibiotic production when cloned at high copy number, questioned whether afsR was a pleiotropic regulatory gene . In this study we demonstrate that multiple copies of afsR can stimulate both Act and Red production and that, despite its homology, it cannot substitute for the pathway-specific regulatory genes . Moreover, an in-frame deletion that removed most of the afsR coding sequence resulted in loss of Act and Red production, and a marked reduction in the synthesis of the calcium-dependent antibiotic (CDA), but only under some (non-permissive) nutritional conditions . Although additional copies of afsR resulted in elevated levels of the actII-ORF4 and redD transcripts, transcription of the pathway-specific regulatory genes under non-permissive conditions was unaffected by deletion of afsR . While afsR may operate independently of the pathway-specific regulatory proteins to influence antibiotic production, the activity of ActII-ORF4 and of RedD under non-permissive conditions could depend on interaction with, or modification by, AfsR.

J Antimicrob Chemother, 1996 Jul, 38 Suppl A, 85 - 96
Antibiotic susceptibility patterns of community-acquired respiratory isolates of Moraxella catarrhalis in western Europe and in the USA . The Alexander Project Collaborative Group; Berk SL et al.; Eight hundred and eighteen Moraxella catarrhalis strains, isolated in 1992 and 1993 at 15 centres in Western Europe and the USA were tested for beta-lactamase production and resistance to 15 antibiotics . The proportion of beta-lactamase producing strains in Europe rose significantly from 70% in 1992 to 82% in 1993, whilst in the USA the increase (85-92%) was not significant . Penicillin and amoxycillin resistance was more prevalent in the USA than in Europe . All penicillin-resistant strains isolated in the USA exhibited beta-lactamase activity, whilst 8% of beta-lactamase-negative strains isolated in Europe were also penicillin resistant . All but three isolates were sensitive to cefaclor, cefuroxime, cefixime and ceftriaxone, all but one were sensitive to ofloxacin and all were sensitive to ciprofloxacin and amoxycillin cluvulanate . Resistance to erythromycin was not encountered, although 19 strains had MICs > or = 0.5 mg/L . Of these, 15 came from European centres . Almost all strains were highly susceptible to clarithromycin, azithromycin, doxycycline and co-trimoxazole.

Mod Midwife, 1996 Jul, 6(7), 14 - 6
Breast feeding and antibiotics; Scott A et al.; At all times the necessity of prescribing to breast feeding mothers should be questioned . The advantages and disadvantages should be carefully assessed for both mother and baby . Whenever possible the long-acting form of the drug should be avoided . The use of drugs with short half lives minimises the risk of accumulation, e.g . Cefotaxime 1.1 hours, Ceftriaxone 7.25 hours . Aim to avoid breast feeding when milk drug concentrations are at their peak . In general, this occurs 1-2 hours following oral medication . As a general principle, advising the administration of medication immediately following a breast feed is the safest option for the baby but this is not true for all drugs . Where information is available, choose the drug which appears in the least concentration in breast milk . All infants should be monitored for uncharacteristic symptoms and signs . If it is essential that a drug with known potential serious toxicity to the infant has to be prescribed to the mother, then breast feeding should be discontinued . As the infant's metabolic and excretory capacities rapidly improve during the first months of life, the risk of toxicity to the infant will decrease with increasing age of the infant.

J Gastroenterol Hepatol, 1996 Jul, 11(7), 681 - 5
Microvascular disturbances in the colonic mucosa in antibiotic-associated haemorrhagic colitis: involvement of platelet aggregation; Yonei Y et al.; An ultrastructural study of the colonic mucosa was performed in four patients with antibiotic-associated haemorrhagic colitis and new findings are reported . Colonoscopy was performed and biopsy specimens were obtained within 24 h of the onset of bloody diarrhoea . Colonoscopy demonstrated diffuse oedematous and haemorrhagic mucosa with erosions and white coat . Light microscopy revealed mucosal haemorrhage and inflammatory cell infiltration . Ultrastructurally, platelet aggregation was frequently present in the lumina of colonic mucosal capillaries, causing engorgement of red blood cells in adjacent microvessels . Mild to severe damage was observed in capillary endothelial cells, including discontinuity of basement membranes, gaps between endothelial cells and the destruction of capillaries . There was no evidence of microvascular spasm . In conclusion, our findings suggest that antibiotics directly or indirectly cause microcirculatory disturbances, which result in tissue damage and haemorrhage, in the colonic mucosa.

Res Virol, 1996 Jul-Aug, 147(4), 213 - 8
Differential effects of a new amphotericin B derivative, MS-8209, on mouse BSE and scrapie: implications for the mechanism of action of polyene antibiotics; Adjou KT et al.; Mice were infected intracerebrally with the bovine spongiform encephalopathy (BSE) or the scrapie agent and treated during 8 weeks postinfection to test the protective effect of a new amphotericin B (AmB) derivative, MS-8209, in experimental transmissible spongiform encephalopathies . The results show that (i) the treatment prolonged the incubation period of both BSE-infected and scrapie-infected mice, (ii) MS-8209 and AmB were much more efficient in delaying the onset of scrapie than that of BSE, and (iii) a delay in Prp-res (proteinase K-resistant prion protein) and GFAP (glial fibrillary acidic protein) accumulation was observed in the brains of scrapie-infected mice, but was not significant in BSE-infected mice . The analysis of the molecular and clinical results strongly suggests a common mechanism of action of this category of drugs on the different transmissible spongiform encephalopathy strains . This could be due to an interaction with the PrP transconformation process leading to the formation of PrP-res.

J Antibiot (Tokyo), 1996 Jul, 49(7), 682 - 8
Mechanism of multiple aminoglycoside resistance of kasugamycin-producing Streptomyces kasugaensis MB273: involvement of two types of acetyltransferases in resistance to astromicin group antibiotics; Hotta K et al.; The biochemical basis for the multiple resistance to aminoglycoside antibiotics (AGs) of kasugamycin-producing Streptomyces kasugaensis MB273 was studied . The strain was resistant to a wide range of deoxystreptamine (DOS)-containing AGs as well as astromicin (ASTM) group antibiotics . These AGs strongly inhibited in vitro polyU-directed polyphenylalanine-synthesis using ribosomes from the strain, while they were acetylated and inactivated by the MB273 cell free extract supplemented with acetyl-CoA . It seemed thus likely that the acetyltransferase activity played a critical role for the multiple AG resistance . The acetylation was selective to AGs with 2'-NH2, suggesting the involvement of aminoglycoside 2'-N-acetyltransferase, AAC (2') . Interestingly, the acetylation of istamycin B (ISM-B; an ASTM group AG) resulted in the formation of two different products (1-N-acetyl ISM-B and 2"-N-acetyl ISM-B) at a similar ratio . In this context, an AAC (2') gene cloned as an ISM-B resistance gene from the strain MB273 directed the conversion of ISM-B to only 1-N-acetyl ISM-B . It seemed likely that two types of AACs {AAC(2') and a novel one} were involved in the mechanism of resistance to ASTM group AGs.

J Antibiot (Tokyo), 1996 Jul, 49(7), 651 - 6
Pyralomicins, novel antibiotics from Microtetraspora spiralis . II . Structure determination; Kawamura N et al.; Novel antibiotics, pyralomicins 1a approximately 1d, 2a approximately 2c were isolated from the culture broth of Microtetraspora spiralis MI178-34F18 . The structures of pyralomicins were determined by various NMR spectral analyses including 1H-15N HMBC and 13C inverted question mark1H inverted question mark NOE difference experiments.

J Antibiot (Tokyo), 1996 Jul, 49(7), 657 - 60
Pyralomicins, novel antibiotics from Microtetraspora spiralis . III . Biosynthesis of pyralomicin 1a; Kawamura N et al.; The biosynthesis of pyralomicin 1a (1) was studied by feeding of 13C and 15N labeled compounds to the culture of Microtetraspora spiralis MI178-34F18 . The result indicated that the benzopyranopyrrole unit of 1 was derived from two units of acetate, one unit of propionate and one unit of proline, and that the cyclitol unit of 1 was derived from glucose metabolites . And 4'-O-CH3 was derived from the S-CH3 group of methionine.

J Antibiot (Tokyo), 1996 Jul, 49(7), 635 - 8
Chlovalicin, a new cytocidal antibiotic produced by Sporothrix sp . FO-4649 . II . Physicochemical properties and structural elucidation; Takamatsu S et al.; A new growth inhibitor of IL-6 responsive MH60 cells, chlovalicin (MW; 332, C16H25O5Cl), was found in cultures of Sporothrix sp . FO-4649, together with a known sesquiterpene, ovalicin . The structure of chlovalicin was elucidated by spectroscopic methods . Chlovalicin possesses a chlorinated methylene moiety at the C-1 position, and it corresponds to halogenated products derived from the epoxide ring attached to the C-1 position of ovalicin . The absolute configuration of chlovalicin was clarified as 1S, 2R, 3S, 1'S, 2'R by chemical transformation from ovalicin.

J Pharmacol Exp Ther, 1996 Jul, 278(1), 205 - 11
The secretory intestinal transport of some beta-lactam antibiotics and anionic compounds: a mechanism contributing to poor oral absorption; Saitoh H et al.; The mechanisms of intestinal permeation of several beta-lactam antibiotics and anionic compounds were studied in vitro using excised rat intestinal segments . Permeation of cefazolin through jejunum, ileum and colon was highly secretory-oriented; serosal-to-mucosal permeation rates were two- to three-fold greater than mucosal-to-serosal permeation rates . Serosal-to-mucosal permeation decreased in the absence of D-glucose, and mucosal-to-serosal permeation increased, indicating that the preferential secretory transport of cefazolin is energy dependent . Ampicillin permeation across rat jejunum also favored secretion, whereas the permeation of cefaclor and cephradine favored absorption . Because cefazolin is anionic, several structurally unrelated anionic compounds were also tested . Of these only phenol red exhibited preferential serosal-to-mucosal permeation . The intestinal permeation of phenol red was concentration dependent and glucose dependent . Verapamil and a monoclonal antibody to P-glycoprotein only modestly and inconsistently affected the permeation of cefazolin, ampicillin and phenol red . Probenecid and guanidine were much more effective inhibitors of cefazolin and phenol red secretion . Mutual interactions between cefazolin and phenol red were also observed . These results show that the rat intestine has the capability for net secretory transport of some hydrophilic, anionic compounds . Transport of these compounds has some of the characteristics of organic anion and organic cation transport systems.

J Bacteriol, 1996 Jul, 178(14), 4281 - 8
Guanosine pentaphosphate synthetase from Streptomyces antibioticus is also a polynucleotide phosphorylase; Jones GH et al.; The gene for the enzyme guanosine pentaphosphate synthetase I (GPSI) from Streptomyces antibioticus has been cloned and sequenced . The cloned gene functioned as a template in the streptomycete coupled transcription-translation system and directed the synthesis of a protein with the properties expected for GPSI . Sequencing of the cloned gene identified an open reading frame of 740 amino acids whose amino terminal sequence corresponded to the N terminus of purified GPSI . The GPSI protein sequence was found to possess significant homology to polynucleotide phosphorylase from Escherichia coli . Indeed, like E . coli polynucleotide phosphorylase, purified GPSI was shown to catalyze the polymerization of ADP and the phosphorolysis of poly(A) . However, the E . coli enzyme was unable to catalyze the synthesis of guanosine pentaphosphate under conditions in which GPSI was highly active in that reaction . Overexpression of the cloned gpsI gene in E . coli led to an increase in both polynucleotide phosphorylase and guanosine pentaphosphate synthetase activities in the cloning host . The polynucleotide phosphorylase activities of GPSI and of the E . coli enzyme were strongly inhibited by dCDP, but the pppGpp synthetase activity of GPSI was not inhibited and indeed was slightly stimulated by dCDP . These results strongly support the identity of GPSI as a bifunctional enzyme capable of both pppGpp synthesis and polynucleotide phosphorylase activities.

Br J Cancer Suppl, 1996 Jul, 27, S52 - 6
Oxygen dependence of the cytotoxicity of the enediyne anti-tumour antibiotic esperamicin A1; Batchelder RM et al.; The enediyne anti-tumour antibiotics are extremely potent cytotoxins, apparently because of their conversion to diradical species which induce DNA double strand breaks with high efficiency . The potency of enediynes suggests their possible utility as effector units for prodrugs which can be activated selectively in tumours, such as bioreductive drugs (BD) or radiation-activated cytotoxins (RAC) . However, the similarity of the radical-induced DNA breakage reactions of the enediynes to those caused by ionising radiation suggested that resistance of hypoxic cells might be a potential problem . Experiments with AA8 cells in culture demonstrated that the enediyne antibiotics neocarzinostatin and esperamicin A, (ESP) are much less toxic under hypoxic than aerobic conditions . Sensitivity to ESP (concentration for 90% cell kill 10 pM) decreased 15-fold under hypoxia, and was partially restored by simultaneous exposure to misonidazole . ESP induced chromosome breakage (micronucleus formation) with an efficiency similar to gamma radiation at equivalent cell kill, suggesting a clastogenic mechanism of cytotoxicity . In contrast, little micronucleus formation was evident after exposure to ESP under hypoxia, even at concentrations giving equivalent cell killing . These findings suggest that resistance of hypoxic cells may limit the utility of enediynes as cytotoxic effectors for BD or RAC prodrug development, and that further investigation of enediynes as anti-tumour agents should include strategies capable of eliminating hypoxic cells.

J Fam Pract, 1996 Jul, 43(1), 56 - 62
Antibiotics and respiratory infections: are patients more satisfied when expectations are met?
Hamm RM, Hicks RJ, Bemben DA.
BACKGROUND: Antibiotics are frequently prescribed for respiratory infections, even though most of these infections are viral . To understand why physicians do so, we studied patients' and physicians' expectations for antibiotics and the effects of the patient-physician interaction on patient satisfaction . METHODS: Patients with a respiratory infection were asked to complete a questionnaire before and after visiting with physicians at three family medicine centers . Physicians completed a questionnaire following the visit . RESULTS: Sixty-five percent of the 113 patients with respiratory infection expected antibiotics . Physicians had some ability to perceive this expectation and frequently prescribed antibiotics for patients who expected them . Antibiotics were prescribed to over 75% of patients with sinusitis or bronchitis and to 18% of those diagnosed with only viral infections . No association was found between a prescription for antibiotics and patient satisfaction; however, patient satisfaction did correlate with the patients' report that they understood the illness and that the physician spent enough time with them . CONCLUSIONS: Physicians frequently prescribe antibiotics for upper respiratory infections when they believe patients expect it, but receiving a prescription for antibiotics is not in and of itself associated with increased patient satisfaction.

Biochem Pharmacol, 1996 Jun 28, 51(12), 1669 - 78
Bioactivation of mitomycin antibiotics by aerobic and hypoxic Chinese hamster ovary cells overexpressing DT-diaphorase; Belcourt MF et al.; DT-Diaphorase catalyzes a two-electron reduction of mitomycin C (MC) and porfiromycin (POR) to reactive species . Many cell lines that overexpress DT-diaphorase and are sensitive to the mitomycins are protected from the aerobic cytotoxicity of these drugs by the DT-diaphorase inhibitor dicumarol . The cytoprotective properties of this relatively non-specific inhibitor, however, vanish under hypoxic conditions . To ascertain the role of DT-diaphorase in mitomycin bioactivation and cytotoxicity in living cells, a rat liver DT-diaphorase cDNA was transfected into Chinese hamster ovary cells . MC was equitoxic to the parental cells under oxygenated and hypoxic conditions . In contrast, POR was less toxic than MC to these cells under aerobic conditions, but significantly more toxic than MC under hypoxia . Two DT-diaphorase-transfected clones displayed increases in DT-diaphorase activity of 126- and 133-fold over parental cells . The activities of other oxidoreductases implicated in mitomycin bioreduction were unchanged . MC was more toxic to both DT-diaphorase-transfected lines than to parental cells; the toxicity of MC to the transfected lines was similar in air and hypoxia . POR was also more toxic to the DT-diaphorase-elevated clones than to parental cells under oxygenated conditions . Under hypoxia, however, the toxicity of POR to the transfected clones was unchanged from that of parental cells . The findings implicate DT-diaphorase in mitomycin bioactivation in living cells, but suggest that this enzyme does not contribute to the differential toxicity of MC or POR in air and hypoxia.

J Mol Biol, 1996 Jun 28, 259(5), 916 - 25
Inhibition of the self-cleavage reaction of the human hepatitis delta virus ribozyme by antibiotics; Rogers J et al.; Human hepatitis delta virus (HDV) poses a health threat in populations where chronic hepatitis B is endemic . It is a single-stranded RNA virus of 1700 nucleotides and both genomic and antigenomic sequences contain ribozymes which are important for viral replication . Using ribozyme constructs we show that several classes of antibiotics inhibit the self-cleavage reaction of the HDV ribozyme . Antibiotics of the aminoglycoside, peptide and tetracycline classes all inhibit HDV cleavage in vitro at micromolar concentrations . Neomycin (an aminoglycoside) inhibits HDV self-cleavage with a Ki value of 28 (+/- 10) microM . Neomycin inhibition can be reversed by increasing magnesium ion concentration in a competitive manner . Lead acetate cleaves positions G76, A42 and G28, which surround the ribozyme cleavage site . Both Mg2+ and neomycin prevent lead cleavage . Footprinting experiments using base-specific chemical probes revealed enhanced modifications of a set of bases by neomycin, overlapping with the above mentioned lead cleavages . These observations may indicate that neomycin directly displaces divalent metal ions essential for catalysis.

Biochemistry, 1996 Jun 18, 35(24), 7974 - 82
Enzymatic and chemical footprinting of anthracycline antitumor antibiotics and related saccharide side chains; Shelton CJ et al.; DNase I and three DNA chemical footprinting agents were used to compare the DNA binding properties of the anthracycline antitumor antibiotics daunomycin, aclacinomycin A, and ditrisarubicin B . These anthracyclines contain a tetracyclic chromophore which intercalates into DNA and a monosaccharide, trisaccharide, and two trisaccharide side chains, respectively . These side chains consist of between one and three 2,6-dideoxy, 1,4-diaxially linked sugars . Three chemical probes, fotemustine, dimethyl sulfate, 4-(2'-bromoethyl)phenol, and the enzymic probe DNase I were used in the footprinting experiments . The chemical probes provided a clear picture of the binding pattern at 37 degrees C and more detailed information than that obtained using the standard DNase I footprinting assay . All three anthracyclines showed preferred binding to 5'-GT-3' sequences in both the chemical and enzymatic footprinting . DNase I footprinting showed that the number of base pairs of DNA protected from cleavage increased with the number of saccharide groups present at particular sites and is consistent with DNA binding of the saccharide side chains . Alkylation of runs of guanine by fotemustine was inhibited by all three anthracyclines, while alkylation by dimethyl sulfate was enhanced for most guanines . The probe 4-(2'-bromoethyl)phenol showed that all three anthracyclines completely protected all of the adenines in the minor groove from alkylation, and enhanced major groove guanine alkylation was observed with aclacinomycin A, daunomycin, and, to a much lesser extent, ditrisarubicin B . These results are consistent with intercalation of the aglycone ring and binding of the rigid, hydrophobic saccharide side chains in the minor groove . Footprinting of four methyl glycosides related to the anthracyclines showed no evidence of DNA binding with any of the agents studied.

Mutat Res, 1996 Jun 10, 360(2), 95 - 100
DNA strand cleavage by tumor-inhibiting antibiotic 6-diazo-5-oxo-L-norleucine; Hiramoto K et al.; A tumor-inhibiting antibiotic, 6-diazo-5-oxo-L-norleucine (DON), caused DNA single-strand breaks . Thus, supercoiled plasmid DNA was transformed into an open circular relaxed form DNA by incubation with DON at pH 7.4 . DNA strand cleavage by DON was not inhibited by superoxide dismutase, but inhibited by catalase . The inhibition by catalase may not be due to the destruction of hydrogen peroxide, but to the masking DON by the interaction with the heme moiety of the enzyme . DNA strand cleavage by DON was inhibited by azide, mannitol, ethanol, cysteine and 2-mercaptoethanol, suggesting the involvement of radical species in the cleavage . The cleavage, however, was not suppressed by removal of dissolved oxygen from the reaction mixture, indicating that no oxygen-derived radicals participated in the cleavage . Electron spin resonance spin-trapping technique using 5,5-dimethyl-1-pyrroline N-oxide (DMPO) and N-tert-butyl-alpha-phenylnitrone (PBN) elucidated the generation of a carbon-centered radical from DON . Hence, the carbon-centered radical may participate in DNA strand cleavage by DON.

Pharm Pract Manag Q, 1996 Jul, 16(2), 41 - 51
Antibiotic streamlining: monitoring and compliance; Norvell M; The principles of antibiotic streamlining are discussed . At the University of Nebraska Medical Center, antibiotic streamlining is conducted through the coordination of decentralized pharmacists and a comprehensive drug-usage evaluation program . Streamlining is focused on reducing redundant antibiotic coverages and converting from i.v . to oral therapy whenever possible . Examples include switching from i.v . to oral ciprofloxacin and reducing the number of ampicillin-sulbactam, clindamycin combinations . Benefits and drawbacks of the program are discussed.

Pharm Pract Manag Q, 1996 Jul, 16(2), 13 - 7
Combination antibiotic therapy in critically ill patients; Jacobi J; Combination antibiotic therapy may be used for a number of reasons in critically ill patients . The potential benefits of combination therapy include prevention of resistance, treatment of polymicrobial infections, to decrease toxicity, or for synergy . Selected literature is reviewed which examines the use of combination therapy in critically ill patients . Research reports have not uniformly demonstrated the benefits of combination therapy . The situations where combination therapy has been beneficial are discussed.

J Dairy Sci, 1996 Jun, 79(6), 1065 - 73
Quality milk and tests for antibiotic residues; Sischo WM; One goal of total quality management is to prevent the occurrence of antibiotics in raw milk shipped from the farm . An effective approach to meet this goal is the implementation of HACCP (Hazard Analysis Critical Control Point) procedures, which are part of the Milk and Dairy Beef Quality Assurance Program for antibiotic avoidance . The program defines 10 critical control points, including screening tests for preventing antibiotic residues . Although milk from individual cows clearly should be tested to ensure that antibiotic-free milk is leaving the farm, it is not clear whether any existing tests can be reliably used on milk samples from individual cows, or even on samples from bulk tanks . The FDA acceptance procedures have not required that bulk milk tests undergo a population evaluation; these tests have not been objectively evaluated for individual cows . Of more concern, detection limits differ among tests, sometimes approaching zero . Despite the intent of the Pasteurized Milk Ordinance, milk acceptability definitions vary between states . In addition, the predictive value of test results has not been integrated into the regulatory process . Although largely ignored by the regulatory agencies, these issues cannot be ignored by the dairy industry . Ultimately, the milk testing program should become a component of the quality process that is centered on the farm and that measures the success of the industry in producing high quality milk rather than being a regulatory program that searches for a flawed product.

Am J Infect Control, 1996 Jun, 24(3), 174 - 9
Measuring antibiotic use in a long-term care facility; Mylotte JM; BACKGROUND: In the long-term care facility setting, there is little information about correlation of antibiotic use with care delivered or with the occurrence of fever or use of Foley catheters . The objectives of this study were to compare various measures of quantitating antibiotic use and to correlate these measures with febrile morbidity and Foley catheter use in a hospital-based, long-term care facility . METHODS: This was a prospective study in which the number of residents with fever (rectal temperature of 100.5 degrees F or greater) or a Foley catheter was documented daily . Antibiotic use was measured in several ways; incidence (courses per 100 resident care days), proportion of resident care days that were antibiotic days, the number of antibiotic courses per month, and the number of residents treated per month . RESULTS: Between January and December 1989, 111 (71%) of 156 residents were prescribed 263 antibiotic courses . Incidence of antibiotic use was 0.61 courses per 100 resident care days . On average only about 5% of resident care days per month were associated with antibiotic use, whereas an average of 18 residents per month received antibiotic therapy . Trimethoprim/sulfa and ciprofloxacin together accounted for 55% of the courses prescribed . No significant correlations were found between any antibiotic use measure and febrile days or Foley catheter days each month . CONCLUSIONS: In the long-term care facility setting, monitoring the number of residents treated with antibiotics per month is a more practical and useful measure of use than measurement of resident care days on antibiotics per month.

J Vet Pharmacol Ther, 1996 Jun, 19(3), 225 - 32
Cardiovascular effects of the macrolide antibiotic tilmicosin, administered alone and in combination with propranolol or dobutamine, in conscious unrestrained dogs; Main BW et al.; Tilmicosin(TM), a macrolide antibiotic and active ingredient in formulated Micotil 300 (Eli Lilly and Co., Indianapolis, IN, USA), is the active ingredient in a formulated animal product used for the treatment of respiratory tract infections in cattle . Owing to the concern of governmental regulatory agencies over the possibility of an accidental injection of the antibiotic to a livestock handler, the cardiovascular effects of sub lethal doses of TM were evaluated in conscious mixed-breed dogs . Left ventricular function, systemic arterial blood pressure, and heart rate (HR) responses to TM alone and in combination with propranolol(P) or dobutamine HCl(DOB) were evaluated . Dogs were instrumented with indwelling micromanometers implanted in the left ventricular chamber and in the thoracic aorta . Cardiovascular variables were recorded, and the peak value of the first derivative of left ventricular pressure (dp/dt(max)) was used as an index of left ventricular inotropic state . Six treatments were randomly assigned to each of the six dogs using a Latin square design . The six treatments were vehicle, TM alone (2.5 mg/kg of body weight), TM immediately followed by P, and TM immediately followed by 1 of 3 dosages of DOB infused for approximately 45 min . Additionally, doses of TM alone (0.25, 1.0, 2.5, and 5.0 mg/kg) were administered to complete a dose-response curve . TM caused dose dependent decreases in (dp/dt(max)) and aortic pulse pressure . HR increased dose-dependently . Left ventricular end-diastolic pressure increased at the 2.5 and 5.0 mg/kg dosages . Left ventricular systolic pressure was reduced dose-dependently at the 2.5 and 5.0 mg/kg dosages . Treatment with P exacerbated the negative inotropic effect and the decrease in left ventricular systolic pressure, but did not attenuate the tachycardia associated with TM treatment . DOB attenuated the changes in ventricular inotropic state in a dose-dependent manner . DOB infusion also restored left ventricular systolic pressure at dosages of 3 or 10 micrograms/min/kg . Our data indicate that toxic doses of TM may have a negative inotropic effect in conscious dogs . HR increased in a dose-dependent manner and was not the result of beta 1-receptor stimulation . DOB reversed some, but not all, of the effects caused by TM administration.

Infect Dis Clin North Am, 1996 Jun, 10(2), 223 - 37
Early empiric antibiotic therapy for febrile neutropenia patients at low risk; Rolston KV et al.; Although it is apparent that certain patients with febrile neutropenic episodes can benefit from outpatient antibiotic therapy, not all low-risk patients are treated in this fashion . There are barriers, real and perceived, to implementing this approach for patients, health care providers, and caregivers . Table 3 summarizes the advantages and disadvantages of ambulatory management of febrile neutropenic patients . For many patients and physicians, outpatient oral antibiotics may be preferred, whereas for others a more conservative approach might be needed in order to feel comfortable with treating this population on an outpatient basis . In this situation, patients can be treated in a stepwise fashion as shown in Table 4 . These alternatives allow physicians and patients options to discuss when planning treatment strategies for febrile neutropenia.

Ann Pharmacother, 1996 Jun, 30(6), 586 - 8
Assessment of the palatability of antistaphylococcal antibiotics in pediatric volunteers; Matsui D et al.; OBJECTIVE: To evaluate the palatability of four commonly prescribed antistaphylococcal antibiotics, cloxacillin, cephalexin, erythromycin, and fusidic acid, in volunteer children . DESIGN: A single-blind taste test of four flavored antibiotic suspensions commonly used in the treatment of skin infections in pediatric patients . SETTING: University teaching hospital . PARTICIPANTS: Twenty healthy volunteer children with a mean age of 9.2 +/- 2.0 SD years (range 6-12) . MAIN OUTCOME MEASURES: The taste of each antibiotic was rated by the children on a 10-cm visual analog scale incorporating a facial hedonic scale . The children were also asked which antibiotic they thought tasted the best and which tasted the worst . RESULTS: Taste scores were as follows: cloxacillin 1.4 +/- 1.8 cm, cephalexin 6.5 +/- 2.7 cm, erythromycin 6.8 +/- 3.0 cm, and fusidic acid 6.3 +/- 2.4 cm . The taste rating of cloxacillin was significantly lower compared with the other three antibiotics (p = 0.001) . Cloxacillin was chosen as having the worst taste by a significant proportion of the children (18 of 20) . None of the antibiotics was clearly best tasting . CONCLUSIONS: Given similar effectiveness, taste considerations may be important in the decision as to which antibiotic to prescribe . The perception that cloxacillin is poor tasting to children is supported by this study, which suggests that when compliance with oral medication is critical for successful treatment, prescription of cloxacillin suspension should be avoided.

Aliment Pharmacol Ther, 1996 Jun, 10(3), 269 - 73
Prospective evaluation of the macrolide antibiotic dirithromycin for the treatment of Helicobacter pylori; Laine L et al.; BACKGROUND: Macrolide antibiotics are active in vitro and in vivo against Helicobacter pylori . We assessed a newer macrolide, dirithromycin, for the treatment of H . pylori in two separate studies . METHODS: Volunteers with H . pylori infection (by 13C-urea breath test) were randomly assigned to 2-week treatment regimens . Study 1: dirithromycin 500 mg q.d.s., dirithromycin 500 mg q.d.s . plus omeprazole 40 mg q.d.s., or dirithromycin 500 mg q.d.s . plus metronidazole 500 mg t.d.s . Study 2: dirithromycin 500 mg q.d.s . plus omeprazole 20 mg b.d., dirithromycin 1000 mg q.d.s . plus omeprazole 20 mg b.d., or amoxycillin 500 mg q.d.s . plus omepirazole 20 mg b.d . Four weeks after the completion of therapy a repeat 13C-urea breath test was done to assess for cure . RESULTS: No patient taking dirithromycin alone (n = 6) or in combination with omeprazole (n = 26) achieved cure of their infection . Eradication of H . pylori was seen in one of seven patients taking dirithromycin plus metronidazole . Five of 10 patients taking omeprazole-amoxycillin dual therapy had their H . pylori infection cured (P = 0.0007 vs . patients taking dirithromycin plus omeprazole) . Eleven (47%) of 32 patients taking dirithromycin alone or combined with omeprazole reported side-effects, but only two (6%) stopped therapy prematurely as a result of side-effects . CONCLUSION: No subject taking dirithromycin alone or in combination with omeprazole had their H . pylori infection cured . Dirithromycin, in the regimen used, shows little promise in the treatment of patients with H . pylori infection.

J Laryngol Otol, 1996 Jun, 110(6), 531 - 3
Per-operative antibiotic/steroid prophylaxis of tympanostomy tube otorrhoea: chemical or mechanical effect?
Shinkwin CA, Murty GE, Simo R, Jones NS.
The per-operative instillation of ototopical antibiotic/steroid drops reduces the incidence of early otorrhoea after tympanostomy tube insertion . Whether this is due to the chemical properties of the antibiotic/steroid or simply the mechanical instillation of fluid is unclear . In this paired matched study of 161 subjects Gentisone HC was shown to significantly reduce the otorrhoea rate compared to normal saline (1.24 per cent compared with 9.32 per cent, p < 0.005, difference 8.07 per cent, 95 per cent confidence interval for difference 3.21 per cent to 12.93 per cent) . Capillary viscosimetry proved Gentisone HC to be more viscous than normal saline . The benefits are due to Gentisone HC's chemical properties, and Gentisone HC rather than normal saline instillation per-operatively is recommended when tympanostomy tubes are inserted.

J Laryngol Otol, 1996 Jun, 110(6), 527 - 30
A cost-benefit analysis of the post-operative use of antibiotic ear drops following grommet insertion; Pearson CR et al.; A prospective randomized controlled study was carried out to investigate the effect of prophylactic antibiotic ear drops used for five days after bilateral grommet insertion . The average improvement in the hearing threshold was significantly better in ears in which there was an effusion (16 dB) compared with no effusion (9 dB) . The drops had no significant effect upon grommet function at three months measured by blockage rates, extrusion rates or improvement in pure tone audiometry whether or not there was an effusion . The drops were not therefore cost-effective.

Kansenshogaku Zasshi, 1996 Jun, 70(6), 591 - 6
{Effect of macrolide antibiotics on airway goblet hypersecretion in guinea pigs}; Tamaoki J et al.; Although macrolide antibiotics have now been widely used in the treatment of chronic airway infections including diffuse panbronchiolitis and chronic bronchitis, the mechanism of the efficacy remains uncertain . Because the increased mucus glycoprotein secretion from airway goblet cells may play a significant role in the development of such diseases, to determine the effects of macrolides on airway goblet cell secretion, we studied guinea pig airways by a semiquantitative morphometric method . The goblet cell secretion was assessed in histological sections of the trachea and main bronchi stained with Alcian blue and PAS by determining mucus score, which is inversely related to the magnitude of mucus discharge . Intravenous IL-8 decreased mucus score in a dose-dependent manner and increased the number of neutrophils present in bronchoalveolar lavage fluid . Oral administration of clarithromycin at a daily dose of 1-10 mg/day for 2 weeks dose-dependently inhibited IL-8 (5 mg/ kg)-induced decrease in mucus score, with the maximal inhibition being 54 +/- 11% (p < 0.001) in the trachea and 48 +/- 8% (p < 0.01) in the main bronchi . This effect was accompanied by the inhibition of neutrophil accumulation into bronchoalveolar lavage fluid . Erythromycin produced similar inhibitory effects on IL-8-induced goblet cell secretion and neutrophil accumulation, whereas amoxicillin and cefaclor had no effect . These results suggest that macrolides protect against goblet cell hypersecretion probably through an inhibition of recruitment of neutrophils into the airway mucosa.

Poult Sci, 1996 Jun, 75(6), 705 - 10
Effects of feed antibiotic avoparcine on organ morphology in broiler chickens; Krinke AL et al.; Groups of 90 male broilers each were administered the antibiotic avoparcine mixed into feed in concentrations of 7.5, 10, and 15 ppm and achieved a higher mean body weight than the controls fed without this admixture . At the end of the 70-d fattening period, histological examination was carried out on selected individuals . The small intestine, liver, bursa of Fabricius, thymus, thyroid gland, pancreas, kidneys, heart, and skeletal muscle were observed on paraffin sections stained with hematoxylin and eosin . Cell proliferation was assessed in the liver and small intestine by means of bromodeoxyuridine labeling . The exposure to avoparcine resulted in a decreased cell proliferation in both tissues when compared to controls . In addition, hypertrophy of the hepatocytes and development of reactive lymphoid tissue in the bursa of Fabricius, which occurred in the controls, were absent in the treated animals . These observations indicate that the growth-promoting effect of avoparcine is related to a restriction in the host animals of responses to intestinal bacteria . No adverse pathological changes were observed in the examined tissues, indicating that avoparcine was well tolerated.

Bull Pan Am Health Organ, 1996 Jun, 30(2), 106 - 17
Prescription of antibiotics for mild acute respiratory infections in children; Gonzalez Ochoa E et al.; Acute respiratory infections (ARI), the leading class of ailments causing people to seek health care, rarely require antibiotics . Nevertheless, many physicians prescribe them needlessly . Hence, reducing the unnecessary use of antibiotics is one aim of any ARI control program . To help determine whether this aim might be achieved through a combination of refresher training for family physicians and public education campaigns, two 1991 interventions were carried out in four health areas (designated A, B, C, and D) in the city of Havana, Cuba . In each area, 10 clinics staffed by family physicians were selected through simple random sampling . In two areas (A and B), a refresher training program on ARI for health personnel was instituted at each clinic, while in areas A and C a community education program was set up . No intervention was carried out in area D . Simultaneously, from January through December 1991 trained individuals visited and administered a standard questionnaire every 15 days to 1,600 families (40 per clinic) systematically selected by random sampling . The aim of this procedure was to record the number of ARI episodes occurring among children under 5 years old, the treatment chosen in these cases, and whether antibiotics were employed . The results showed that when the two interventions were initiated, antibiotics were prescribed for 26%, 20%, 11%, and 19% of the mild ARI cases occurring in areas A, B, C, and D respectively (P > 0.05) . In the period immediately following the interventions, antibiotic prescription rates declined by 26% and 63% in areas A and B, while increasing by 2% and 48% in areas C and D . Overall, prescription of antibiotics in the intervention areas A and B combined decreased by 54% (95% CI: 31-69%) . These data suggest that a refresher training program for health personnel can rapidly reduce the unnecessary prescribing of antibiotics for ARI cases, but that public education alone does not appear effective.

Ann Rheum Dis, 1996 Jun, 55(6), 383 - 7
Protection against peroxynitrite dependent tyrosine nitration and alpha 1-antiproteinase inactivation by some anti-inflammatory drugs and by the antibiotic tetracycline; Whiteman M et al.; OBJECTIVE: To examine in vitro the ability of several drugs to protect against deleterious effects of peroxynitrite, a cytotoxic agent formed by reaction of nitric oxide with superoxide radical, that may be generated in the rheumatoid joint and could cause joint damage . METHODS: The ability of several drugs to protect against such possible toxic actions of peroxynitrite as inactivation of alpha 1-antiproteinase and nitration of tyrosine was evaluated . RESULTS: Most non-steroidal anti-inflammatory drugs were moderately (indomethacin, diclofenac, naproxen, tolmetin) or only weakly (sulindac, ibuprofen, aurothioglucose, flurbiprofen, sulphasalazine, salicylate, penicillamine disulphide) effective in preventing tyrosine nitration and alpha 1-antiproteinase inactivation by peroxynitrite, but 5-aminosalicylate and penicillamine were much more effective, as was the antibiotic tetracycline (but not ampicillin) . Phenylbutazone and flufenamic acid protected effectively against tyrosine nitration, but could not be tested in the alpha 1-antiproteinase system . The analgesic paracetamol was highly protective in both assay systems . CONCLUSION: Many drugs used in the treatment of rheumatoid arthritis are unlikely to act by scavenging peroxynitrite . The feasibility of peroxynitrite scavenging as a mechanism of penicillamine, 5-aminosalicylate, and paracetamol action in vivo is discussed.

J Bacteriol, 1996 Jun, 178(11), 3402 - 5
redD and actII-ORF4, pathway-specific regulatory genes for antibiotic production in Streptomyces coelicolor A3(2), are transcribed in vitro by an RNA polymerase holoenzyme containing sigma hrdD; Fujii T et al.; redD and actII-ORF4, regulatory genes required for synthesis of the antibiotics undecylprodigiosin and actinorhodin by Streptomyces coelicolor A3(2), were transcribed in vitro by an RNA polymerase holoenzyme containing sigma hrdD . Disruption of hrdD had no effect on antibiotic production, indicating that redD and actII-ORF4 are transcribed in vivo by at least one other RNA polymerase holoenzyme . These data provide the first experimental evidence that HrdD can function as a sigma factor.

Am J Gastroenterol, 1996 Jun, 91(6), 1251 - 3
Pylephlebitis: a case report and review of outcome in the antibiotic era; Saxena R et al.; Pylephlebitis or septic thrombophlebitis of the portal vein, a precursor of hepatic abscesses, is an extremely rare and frequently fatal complication of diverticulitis . The following report describes a patient presenting with pylephlebitis and complicated diverticulitis . Diagnosis was confirmed by computed tomography . The patient had a favorable outcome with medical and surgical therapy, prompting us to evaluate historical treatment of pylephlebitis.

J Am Coll Surg, 1996 Jun, 182(6), 509 - 14
Efficacy of an intraperitoneal antibiotic to reduce the incidence of infection in the trauma patient: a prospective, randomized study; Yelon JA et al.; BACKGROUND: Antibiotic therapy in patients with blunt trauma remains an area of investigation . This study was undertaken in trauma patients evaluated with diagnostic peritoneal lavage to determine the effect of an intraperitoneal antibiotic on the following factors: infectious complications, length of hospital stay, and mortality . METHODS: A prospective, randomized double-blinded study compared using either 500 mg of intraperitoneal kanamycin or a saline control in 69 adult trauma patients requiring diagnostic peritoneal lavage was conducted over a 24-month period . Advanced trauma life support indications for performing diagnostic peritoneal lavage were used . Patients were randomized to receive 50 mL of solution intraperitoneally through a lavage catheter and were evaluated for all septic complications, length of hospital stay, and outcome . RESULTS: Over a 24-month period, 40 patients received kanamycin, and 29 patients received a placebo . Of patients receiving kanamycin, 27.5 percent experienced infectious complications compared to 65.5 percent of the control patients (p = 0.001, chi-square analysis) . The average length of stay in the intensive care unit was 4.18 days in the kanamycin group and 6.96 days in the control group (p = 0.04, chi-square analysis) . The average length of stay was 12.32 days for patients receiving kanamycin and 17.36 days for the control group (p = 0.03, chi-square analysis) . The mortality rate for each group was 13 percent . CONCLUSIONS: Intraperitoneal kanamycin given to trauma patients requiring diagnostic peritoneal lavage within the first three hours following injury reduces the incidence of infectious complications and shortens intensive care unit and hospital stay.

J Chromatogr A, 1996 May 31, 735(1-2), 375 - 85
Studies of the degradation products of nisin, a peptide antibiotic, using capillary electrophoresis with off-line mass spectrometry; Cruz L et al.; The utility of capillary electrophoresis (CE) for assessing the purity and stability of pharmaceutical peptides is investigated . The degradation of nisin, a pentacyclic peptide antibiotic, depends upon sample preparation and storage conditions and is followed by CE . With conventional UV detection, peaks are not identified and unresolved components are not detected . Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOFMS) of isolated CE fractions provides molecular mass information that aids in identification of the nisin degradants and determination of peak purity . The purity of pure and degraded nisin in the absence of any separation is also determined using electrospray ionization mass spectrometry (ESI-MS) and MALDI-TOFMS.

Presse Med, 1996 May 18, 25(17), 793 - 7
{Community-acquired pneumonia in children: importance of Mycoplasma pneumoniae infections and efficacy of antibiotics}; Gendrel D et al.; OBJECTIVES: Define a therapeutic management schema adapted to children with community-acquired pneumonia . METHODS: A prospective survey was conducted in 104 children over 18 months of age with community-acquired pneumonia . The pathogen was isolated in 85% of the cases . RESULTS: Viral infection alone was proven in 30 children (respiratory syncytial virus in 10) . Pneumococci pneumonia was found in 12 patients; the isolated strains were sensitive to penicillin . Apyrexia was obtained in 11/12 cases with amoxicillin . Mycoplasma infections occurred in 42% of the cases (41 alone and in association with pneumococci in 2 cases) . Pneumococci and mycoplasma infections could not be differentiated with standard radiography and laboratory tests . Initial treatment with beta lactamines was always unsuccessful in children with mycoplasma infections . Apyrexia was achieved when antibiotics were changed to macrolides . CONCLUSION: Since lower respiratory tract infections due to pneumococci are much more severe than those due to mycoplasma, beta lactamines should be given as first intention treatment for children over 18 months with pneumonia . Macrolides should be given in case of failure because mycoplasma would then be the most probable infectious agent.

J Mol Biol, 1996 May 10, 258(3), 457 - 79
DNA bending and unwinding associated with actinomycin D antibiotics bound to partially overlapping sites on DNA; Chen H et al.; Actinomycin D (ActD) is a potent anti-tumor antibiotic, that preferentially targets (G-C).(G-C) steps on duplex DNA . We have reported on the solution structure of the ActD-d(A-A-A-G-C-T-T-T) complex (one drug per duplex) based on a combined application of NMR and molecular dynamics calculations . This study established that ActD binds to DNA through intercalation of the phenoxazone chromophore between (G-C).(G-C) steps with the benzenoid and quinonoid-linked cyclic pentapeptide lactone rings spanning two base-pairs in opposite directions in the minor groove of the helix . This research is now extended to the binding of two ActD molecules to adjacent complexation sites within a (G-C-G-C).(G-C-G-C) segment in the self-complementary d(A1-A2-G3-C4-G5-C6-T7-T8) duplex . The occupation of the central (C4-G5).(C4-G5) segment between the two intercalation sites by the inwardly pointing cyclic pentapeptide lactone rings from adjacent bound ActD molecules should result in a potential steric clash in the center of the helix . The NMR data and its analysis on the ActD-d(A-A-G-C-G-C-T-T) complex (two drugs per duplex) establish that two ActD molecules intercalate into symmetry-related (G3-C4).(G5-C6) steps with their attached benzenoid and quinonoid cyclic pentapeptide lactone rings positioned in the minor groove and directed towards the center and the ends of the helix, respectively . The solution structure of the complex was solved by using NMR restraints to guide distance geometry-simulated annealing and restrained molecular dynamics calculations including intensity-based refinements . The DNA helix exhibits a pronounced kink and is fully unwound at the central (C4-G5).(C4-G5) step which results in an opening and widening of the minor groove to generate additional space for accommodation of the inwardly pointing benzenoid cyclic pentapeptide lactone rings in the complex . The outwardly and inwardly pointing cyclic pentapeptide lactone rings of symmetry-related ActD molecules retain similar conformations with the largest difference observed for the L-MeVal residues in the complex . The present study defines how structural changes primarily in the DNA associated with the directional bending of the helix towards the major groove and away from the bound drug opens up and widens the minor groove to accommodate two intercalated ActD molecules bound at partially overlapping sites on the DNA.

Antibiot Khimioter, 1996 May, 41(5), 25 - 9
{Entrapment of antibiotics in liposomes containing phosphatidylethanol}; Davydov VIu et al.; Antibiotic entrapment to liposomes containing phosphatidyl ethanol, a negatively charged phospholipid, as a lipid component was studied . Antibiotics of various groups such as doxorubicin, rifampicin and doxycycline were entrapped to liposomes consisting of a mixture of phosphatidyl choline and phosphatidyl ethanol at a ratio of 1:1 (v/v) or phosphatidyl choline alone . It was shown that the liposomes containing phosphatidyl ethanol were able to entrap the antibiotics in higher amounts by comparison with the liposomes containing phosphatidyl choline . Phosphatidyl ethanol in the composition of the liposomes had the highest effect on the entrapment of doxorubicin.

Vopr Virusol, 1996 May-Jun, 41(3), 138 - 41
{Strategy for choosing antibiotics for treating bacterial infections associated with chronic tick-borne encephalitis}; Malenko GV et al.; The capacity of wide-spectrum antibiotics kefzol and ristomycin to activate the persisting tick-borne encephalitis (TBE) virus and cause an exacerbation of chronic process was investigated in Syrian hamsters in whom a prolonged (77 to 270 days) persistent TBE infection was induced by three TBE strains: Vasilchenko, V-383, and 205 . The degree of antibiotic-induced activation was assessed using the criteria characterizing the reproduction and peculiarities of persisting TBE virus, immunodepression, and morphologic changes in the central nervous system . Effects of kefzol and ristomycin were compared with those of 8 antibiotics studied previously . Ristomycin, levomycetin (chloramphycin), penicillin, ampicillin (ampital), and levoridan were referred to drugs devoid of evident provoking effect . Kefzol (cefamezin), florimycin (viomycin), and kanamycin (kanamytrex) were characterized as weak activators and streptomycin and tetracycline as potent activators of the persisting TBE virus . These data may be used when selecting alternative agents for therapy of secondary bacterial infections concomitant with TBE.

Biomed Chromatogr, 1996 May-Jun, 10(3), 117 - 21
Determination of hydrophobicity parameters of antibiotics by reversed-phase chromatography . The effect of support; Cserhati T et al.; The hydrophobicity and specific hydrophilic surface area of 29 antibiotics were determined by reversed-phase thin-layer chromatography using impregnated silica and alumina supports and methanol:water mixtures as eluents . It was found that the supports retain their original retention characteristics even after impregnation influencing the reversed-phase retention of antibiotics . It was established that the hydrophobicity parameters are intercorrelated both on impregnated silica and alumina layers, indicating that antibiotics behave as a homologous series of solutes . However, the correlations were not strong enough to substitute the parameters with each other in quantitative structure-activity relationship studies . The specific hydrophobic surface areas determined on impregnated silica and alumina showed no significant correlation, proving the decisive role of support characteristics in the determination of this parameter.

Obstet Gynecol Surv, 1996 May, 51(5), 324 - 8
Utility of antibiotic therapy in preterm premature rupture of membranes: a meta-analysis; Ananth CV et al.; The optimal management of preterm premature rupture of membranes (PROM) is controversial . Maternal risks must be weighed against fetal benefit when expectant management is considered . Despite concerns about maternal harm, protocols of expectant management seem to afford the best perinatal outcomes . Given that infection often is the common pathway for delivery in preterm PROM, recent reports have explored the utility of maternal administration of antibiotics . In this paper we will summarize these results using meta-analytic techniques and assess the impact of antibiotic therapy on maternal and perinatal outcomes.

J Antimicrob Chemother, 1996 May, 37(5), 1023 - 9
Safe intravenous antibiotic therapy at home: experience of a UK based programme; Kayley J et al.; Outpatient i.v . antibiotic therapy is well developed in the United States, largely because of pressures from third-party payers to reduce costs of medical care . We have developed an outpatient i.v . antibiotic programme in Oxford, that has evolved from a desire to provide high quality i.v . therapy to AIDS patients with cytomegalovirus retinitis . We describe the rationale of the service and report on our first two years' experience . We treated 67 consecutive patients (eight with HIV infection) at home with i.v . antibiotics . This resulted in a saving of 2275 hospital days for those patients without HIV infection . HIV positive patients received 69 months of home i.v . therapy . Minor intravascular catheter complications occurred in only five patients (7.5%) . The only serious complications were three episodes of catheter-related sepsis (4.5%), all occurring in AIDS patients who had lines in for more than six months . We have shown that home i.v . antibiotic therapy can be delivered safely to patients with a wide variety of infectious problems using the existing network of community nurses in the National Health Service . Essential components to the programme include a multidisciplinary team working between the hospital and community and a written shared care protocol . Such a programme can result in reduced lengths of hospital stay and patient, community nurse and physician satisfaction.

J Int Med Res, 1996 May-Jun, 24(3), 229 - 38
Pan-European survey of patients' attitudes to antibiotics and antibiotic use; Branthwaite A et al.; This study was carried out to determine patient perceptions of respiratory tract infections and attitudes to taking antibiotics, thus helping doctors to have a better understanding of their patients and their requirements . Telephone interviews were conducted in the UK, Belgium, France, Italy, Spain and Turkey using standardized questionnaires directed at patients who had taken an antibiotic or given one to their child for a respiratory tract infection within the previous 12 months . Approximately 200 working adults (< or = 55 years), 200 elderly adults (> 55 years) and 200 mothers of children (< 12 years) from each country were contacted; in total, 3610 subjects . Pressure on GPs to prescribe antibiotics was highlighted by over 50% of interviewees' believing that they should be prescribed for most respiratory tract infections . Although interviewees were positive about antibiotics, with over 75% judging them to be effective and to speed recovery, some ambivalence was shown . Most patients waited 2-3 days before consulting their doctor and over 80% of respondents expected symptoms to improve after 3 days' treatment . This provided a natural watershed for compliance, with most defaulters stopping after 3 days because they felt better . Second only to fewer side-effects, patients ranked shorter and more convenient dosage alongside efficacy as the improvements most sought in antibiotic therapy . In conclusion, patients regarded antibiotics as important in the treatment of respiratory tract infections, with interest shown in short-course, once-daily therapy . Doctors, however, need to reassure patients that short courses will eradicate infections and have minimal adverse effects on the immune system.

Biosci Biotechnol Biochem, 1996 May, 60(5), 906 - 8
Aclacinomycin X, a novel anthracycline antibiotic produced by Streptomyces galilaeus ATCC 31133; Kim HS et al.; A new anthracycline antibiotic, designated as aclacinomycin X, was isolated from the culture broth of Streptomyces galilaeus ATCC 31133, and was identified as 7-(O-rhodosaminyl-deoxyfucosyl-rednosyl)- aklavinone . Its in vitro cytotoxicity was tested against several human tumor cell lines.

J Antibiot (Tokyo), 1996 May, 49(5), 478 - 84
Synthesis and modification of a novel 1 beta-methyl carbapenem antibiotic, S-4661; Iso Y et al.; We describe an efficient method for introducing a sulfamoylamino group into the C-2' position of pyrrolidine using the Mitsunobu reaction . S-4661, its N-methyl analogues and stereoisomers were synthesized using this method and their structure-activity relationships were investigated.

Obstet Gynecol, 1996 May, 87(5 Pt 2), 884 - 90
Antibiotics at the time of induced abortion: the case for universal prophylaxis based on a meta-analysis; Sawaya GF et al.; OBJECTIVE: To determine the efficacy of periabortal antibiotics in preventing postabortal upper genital tract infection using data from published trials . DATA SOURCES: We performed a literature search of all studies published from January 1966 to September 1, 1994, using MEDLINE, and we manually searched bibliographies of published articles . MEDLINE search terms included: abortion, infection, prophylaxis, antibiotics, pelvic inflammatory disease (PID), and suction curettage . METHODS OF STUDY SELECTION: Randomized, controlled trials comparing antibiotics with placebo in women undergoing suction curettage abortion before 16 weeks' gestation were identified . TABULATION, INTEGRATION, AND RESULTS: Data were extracted independently by two reviewers, one of whom was blinded to journal, year of publication, authors, and institution . Data from 12 studies were combined using meta-analytic techniques based on a fixed-effects model . The overall summary relative risk (RR) estimate for developing postabortal upper genital tract infection in women receiving antibiotic therapy compared with those receiving placebo was 0.58 (95% confidence interval {CI} 0.47-0.71) . Of high-risk women, those with a history of PID had a summary RR estimate of 0.56 (95% CI 0.37-0.84); women with a positive chlamydia culture at abortion had a summary RR estimate of 0.38 (95% CI 0.15-0.92) . Of low-risk women, those with no reported history of PID had a summary RR estimate of 0.65 (95% CI 0.47-0.90); in women with a negative chlamydia culture, the summary RR estimate was 0.63 (95% CI 0.42-0.97) . The lowest summary RR estimate was among women drawn from populations with a low incidence (5-6%) of postabortal infection (summary RR estimate 0.22, 95% CI 0.11-0.42) . The overall 42% decreased risk of infection in women given periabortal antibiotics is similar to the risk reduction demonstrable when only studies published before 1985 are combined (summary RR estimate 0.63, 95% CI 0.44-0.89) . CONCLUSION: Our meta-analysis revealed a substantial protective effect of antibiotics in all subgroups of women undergoing therapeutic abortion, even women in low-risk groups . No more placebo-controlled trials should be performed, because women assigned to placebo are exposed to preventable risk . Routine use of periabortal antibiotics in the United States may prevent up to half of all cases of postabortal infections.

J Natl Med Assoc, 1996 May, 88(5), 289 - 94
Knowledge, beliefs, and use of prescribed antibiotic medications among low-socioeconomic African Americans; Kandakai TL et al.; This study examined knowledge, beliefs, and use of prescribed oral antibiotics of 163 low-socioeconomic African-American adults in a large midwestern city . The effects of age, education, and gender on knowledge and use of antibiotics were examined . Slightly more than 65% of the subjects in this study preferred using brand-name antibiotics . Females were more likely to report using all of their prescribed antibiotics, while males and those in the older age category were more likely to report using antibiotics only until the problem stopped . Twenty-three percent of the males and 18% of the females reported sharing their antibiotics with someone . Less than half of the respondents reported using physicians (and other health professionals) as a major source of information on prescribed antibiotics . Respondents often incorrectly identified painkillers and other medications as antibiotics . Based on these results, it appears that more education is needed to improve patients' understanding of antibiotic regimens.

Neurology, 1996 May, 46(5), 1451 - 4
Cure of a solitary brainstem abscess with antibiotic therapy: case report; Fulgham JR et al.; A solitary brainstem abscess is uncommon . The use of antibiotics and surgical aspiration or excision of a brainstem abscess has resulted in survivors . Survival after treatment of a brainstem abscess with antibiotics alone has been reported rarely, and we present the eighth study case . The patient made an excellent recovery after 12 weeks of antibiotics, with 8 weeks completed as an outpatient . Medical management of a solitary brainstem abscess in an immunocompetent patient is feasible and may result in a complete cure with antibiotics only . Completion of IV antibiotics as an outpatient is viable and cost-effective in selected patients.

J Pharmacol Exp Ther, 1996 May, 277(2), 831 - 9
Transport characteristics of differently charged cephalosporin antibiotics in oocytes expressing the cloned intestinal peptide transporter PepT1 and in human intestinal Caco-2 cells; Wenzel U et al.; To investigate whether multiple peptide transporters mediate absorption of beta-lactams carrying different charges at physiological pH, we used the human intestinal cell line Caco-2 and Xenopus laevis oocytes expressing the cloned rabbit intestinal peptide transporter PepT1 . Characteristics of transport of the anionic cefixime and the zwitterionic cefadroxil were assessed by 1) flux studies using radiolabeled compounds, by 2) measuring changes in pHin in cells and oocytes as a consequence of substrate-mediated proton influx and 3) by applying the two-electrode voltage clamp technique to assess the electrophysiological phenomena associated with beta-lactam transport in oocytes expressing PepT1 . Both beta-lactams were rapidly taken up into Caco-2 cells and oocytes expressing PepT1 by a pH-dependent and saturable transport pathway . Mutual inhibition suggested that acidic and zwitterionic compounds may share a common transporter . Cefixime and cefadroxil caused a significant decline in intracellular pH as a consequence of proton coupled substrate influx . Uptake of cefixime and cefadroxil via PepT1 expressed in oocytes was electrogenic indicating that transport of both beta-lactams is associated with movement of net positive charge . The more acidic pH required for rheogenic cefixime uptake in both cell systems, when compared to cefadroxil uptake in both cell systems, when compared to cefadroxil uptake, and the concomitant faster intracellular acidification indicates that cefixime most likely is taken up only in its nonionized form with an additional proton being cotransported . This is supported by the observation that cefixime uptake at different pH correlated significantly with the percentage of the nonionized species being present . From our studies we conclude that a single peptide transport system can mediate electrogenic uptake of the neutral form of beta-lactam antibiotics into intestinal epithelial cells.

J Chromatogr B Biomed Appl, 1996 Apr 26, 679(1-2), 137 - 45
On-line metal chelate affinity chromatography clean-up for the high-performance liquid chromatographic determination of tetracycline antibiotics in animal tissues; Stubbings G et al.; An on-line high-performance liquid chromatographic (HPLC) method for the determination of tetracycline, oxytetracycline, chlortetracycline and demeclocycline using metal chelate affinity chromatography-reversed-phase HPLC has been developed . The drugs were extracted with succinate buffer and the extract diluted with EDTA-pentanesulphonate buffer . Diluted extract was then absorbed onto a C8 or XAD-2 solid-phase extraction (SPE) cartridge and eluted with methanol . The eluate was then injected onto a TSKgel chelate column which had been preloaded with copper(II) . The tetracyclines were eluted from this column onto the analytical column (Polymer Labs . PLRP-S) with an EDTA-containing buffer . Elution of the analytical column was via a methanol-acetonitrile gradient and detection was by UV at 350 nm . Average recoveries at the 10, 20, 50 and 300 micrograms kg-1 levels were 50-80% . The limit of detection (LOD) was 10 micrograms kg-1 for oxytetracycline and tetracycline and 20 micrograms kg-1 for chlortetracycline and demeclocycline . The method was validated for sheep liver and cattle kidney.

Microbiology, 1996 Apr, 142 ( Pt 4), 741 - 6
Two multifunctional peptide synthetases and an O-methyltransferase are involved in the biosynthesis of the DNA-binding antibiotic and antitumour agent saframycin Mx1 from Myxococcus xanthus; Pospiech A et al.; Saframycin Mx1 is a DNA-binding antibiotic and antitumour agent produced by Myxococcus xanthus . It is a heterocyclic quinone, thought to be synthesized via the linear peptide intermediate AlaGlyTyrTyr . Analysis of 14.1 kb DNA sequence involved in saframycin production revealed genes for two large multifunctional peptide synthetases of 1770 and 2605 amino acids, respectively, and a putative O-methyltransferase of 220 amino acids . The three ORFs read in the same direction and are separated by short non-translated gaps of 44 and 49 bp . The peptide synthetases contain two amino-acid-activating domains each . The first domain lacks two of the most conserved 'core' sequences, and the last domain is followed by a putative reductase functionality, not previously seen in peptide synthetases . Complementation tests showed that antibiotic-non-producing mutant strains lacking one of the peptide synthetases secrete a substrate, presumably a modified amino acid precursor, that can be used by O-methyltransferase-deficient mutant strains to synthesize saframycin Mx1.

Antimicrob Agents Chemother, 1996 Apr, 40(4), 899 - 903
Effects of inhibitors of protein synthesis on lysis of Escherichia coli induced by beta-lactam antibiotics; Rodionov DG et al.; The role of protein synthesis in ampicillin-induced lysis of Escherichia coli was investigated . The inhibition of protein synthesis through amino acid deprivation resulted in the rapid development of ampicillin tolerance as a consequence of the stringent response, as previously reported . In contrast, inhibition of protein synthesis by use of ribosome inhibitors such as chloramphenicol did not readily confer ampicillin tolerance and, in fact, promoted the development of both stages of the ampicillin-induced lysis process, i.e., (i) an ampicillin-dependent stage which apparently involves the interaction of penicillin-binding proteins with ampicillin and (ii) an ampicillin-independent stage which may represent the events leading to the deregulation of peptidoglycan hydrolase activity . We propose that lysis was facilitated when protein synthesis was inhibited because the production of new penicillin-binding proteins to replace those which were ampicillin inhibited was prevented under these conditions.

Pancreas, 1996 Apr, 12(3), 298 - 302
Infected pancreatic necrosis and peripancreatic fluid collections: serendipitous response to antibiotics and medical therapy in three patients; Dubner H et al.; Three patients with clinical and radiologic evidence of pancreatic necrosis or peripancreatic fluid collections/inflammatory masses who were advised to have surgery on the basis of bacterial infection on skinny-needle aspiration of the pancreas but were deemed medically unstable or refused operative intervention were treated with intensive antibiotic therapy . All three patients survived the attack of acute pancreatitis with infection on medical therapy alone . This suggests that occasional patients with infected necrosis and/or peripancreatic collections/inflammatory masses may respond to antibiotics, especially those antibiotics that have recently been shown to have a high penetration into pancreatic tissue.

J Cataract Refract Surg, 1996 Apr, 22(3), 385 - 9
Antibiotic irrigation of the capsular bag to resolve low-grade endophthalmitis; Busin M; Chronic, low-grade endophthalmitis after cataract surgery with intraocular lens (IOL) implantation is often unresponsive to antibiotic therapy, probably because of low drug penetration into the capsular bag . To increase the drug concentration at the infection site, we irrigated the capsular bag with antibiotics . Within 6 weeks, endophthalmitis resolved in three consecutive patients with positive aqueous cultures . Visual acuity improved from finger counting or less to 20/40 or better in all cases . No recurrence was seen in the 12 to 19 month follow-up . Antibiotic irrigation of the capsular bag can resolve chronic, low-grade endophthalmitis in culture-positive patients unresponsive to the same drugs administered by other routes, including conventional intraocular injection . With this approach there is minimal surgical trauma and the IOL is retained.

Gene Ther, 1996 Apr, 3(4), 350 - 6
Novel, high expressing and antibiotic-controlled plasmid vectors designed for use in gene therapy; Liang X et al.; The promise of effective gene therapy can only be accomplished by high-level expression and regulatable delivery of gene products . To achieve this end, a eukaryotic expression plasmid was modified to make transcription dependent on a tetracycline(Tc)-regulated chimeric transactivator . Mouse muscle injected with this two plasmid cis/trans control system expressed reporter proteins at levels five- to 10-fold greater than the cytomegalovirus immediate-early promoter-controlled parental plasmid . Tetracycline could be useful to either repress or activate transactivator-controlled expression based on the position of the tetO control sequences within the reporter plasmid . Finally, a prototype single plasmid construct was made and shown to express a self-regulating bicistronic transcript containing both the reporter and the transactivator . These Tc-controlled plasmids, termed maximum expression and regulated vectors (MERVs), have the potential to target a variety of gene therapy applications.

Aliment Pharmacol Ther, 1996 Apr, 10(2), 211 - 3
Comparison of two lansoprazole-antibiotic combinations (amoxycillin or classical triple therapy) for treatment of H . pylori infection in duodenal ulcer patients; Parente F et al.; AIM: To compare the eradicating capacity of two different antibiotic-lansoprazole combinations (amoxycillin vs . standard triple therapy) with that of lansoprazole alone in Helicobacter pylori-positive duodenal ulcer patients . METHODS: Ninety-six out-patients with H . pylori-positive duodenal ulcer were randomly assigned to receive one of the following three antiulcer regimens: (1) lansoprazole 30 mg b.d . for 4 weeks plus amoxycillin 1 g t.d.s . during the last 2 weeks; or (2) lansoprazole 30 mg once daily for 4 weeks plus classical triple therapy (tripotassium dicitratobismuthate 240 mg b.d., amoxycillin 1 g t.d.s . and tinidazole 500 mg b.d.) for the last 2 weeks; or (3) lansoprazole 30 mg once daily for 4 weeks . Endoscopy was repeated at the end of treatment and 1 month later . A rapid urease test and histology were used to determine H . pylori status . RESULTS: Duodenal ulcer healing rates at 4 weeks were 96% after both lansoprazole with amoxycillin, and lansoprazole with triple therapy, and 97% after lansoprazole alone . Eradication of H . pylori was significantly better with lansoprazole with triple therapy than with either lansoprazole with amoxycillin or lansoprazole alone (90% vs . 55% vs . 3%, respectively) . CONCLUSION: Classical triple therapy combined with lansoprazole is significantly more effective than the lansoprazole with amoxycillin combination for the eradication of H . pylori in duodenal ulcer patients pre-treated with lansoprazole.

Pharm Res, 1996 Apr, 13(4), 588 - 93
Preparation and characterization of freeze-dried chitosan-poly(ethylene oxide) hydrogels for site-specific antibiotic delivery in the stomach; Patel VR et al.; PURPOSE . The purpose of this study was to develop novel drug delivery systems with pH-sensitive swelling and drug release properties for localized antibiotic delivery in the stomach . METHODS . The drug delivery systems were synthesized by crosslinking chitosan and poly(ethylene oxide) (PEO) in a blend to form semi-interpenetrating polymer network (semi-IPN) . Scanning electron microscopy was used to compare the surface and bulk morphology of the freeze-dried and air-dried chitosan-PEO semi-IPN . The hydrogels were allowed to swell and release the antibiotics--amoxicillin and metronidazole--in enzyme-free simulated gastric fluid (SGF, pH 1.2) and simulated intestinal fluid (SIF, pH 7.2) at 37 degrees C . RESULTS . Freeze-dried chitosan-PEO semi-IPN with a porous matrix had swollen extensively as compared to the air-dried hydrogel . The swelling ratio of freeze-dried and air-dried chitosan-PEO semi-IPN after 1 h in SGF was 16.1 and 2.30, respectively . More than 65% of the entrapped amoxicillin and 59% of metronidazole were released from the freeze-dried chitosan-PEO semi-IPN after 2 h in SGF . CONCLUSIONS . The results of this study suggest that freeze-dried chitosan-PEO semi-IPN could be useful for localized delivery of antibiotics in the acidic environment of the gastric fluid.

Pharm Res, 1996 Apr, 13(4), 523 - 7
Characterization of the transport properties of a quinolone antibiotic, fleroxacin, in rat choroid plexus; Ooie T et al.; PURPOSE . It is reported that the cerebrospinal fluid (CSF) to plasma unbound concentration ratio of fleroxacin at steady-state is approximately 0.5 in experimental animals . These results can be accounted for by assuming the presence of an active transport system for the efflux of this compound across the choroid plexus . In the present study, the transport system for fleroxacin was characterized in isolated rat choroid plexus . METHODS . Choroid plexus was isolated from the lateral ventricles of rats . The accumulation of {14C} fleroxacin or {3H} benzylpenicillin by the choroid plexus was examined by the centrifugal filtration method . RESULTS . The accumulation of {14C} fleroxacin by the rat isolated choroid plexus was significantly inhibited by metabolic inhibitors (rotenone, 30 microM and carbonyl cyanide rho-trifluorometh oxyphenylhydrazone (FCCP), 100 microM) and sulfhydryl reagent (p-chloromercuribenzenesulfonic acid (PCMBS), 100 microM) . This accumulation was composed of a saturable component (Vmax = 240 pmol.min-1.microliter tissue-1, Km = 664 microM) and non-saturable one (P = 0.424 min-1.microliter tissue-1) . Accumulation of fleroxacin was competitively inhibited by benzylpenicillin and probenecid with Ki values of 29 microM and 51 microM, respectively . These values are comparable with the Km of benzylpenicillin transport and the Ki of probenecid for the benzylpenicillin transport at the choroid plexus, respectively . Furthermore, fleroxacin inhibited competitively the accumulation of {3H} benzylpenicillin with a Ki of 384 microM, a value comparable with the Km of {14C} fleroxacin transport . CONCLUSIONS . Fleroxacin and benzylpenicillin showed mutual competitive inhibition, suggesting that both are transported via a common transport system in the choroid plexus and are pumped out from CSF into the circulation.

Am J Gastroenterol, 1996 Apr, 91(4), 695 - 700
Omeprazole coupled with two antibiotics for Helicobacter pylori eradication and prevention of ulcer recurrence; Porro GB et al.; BACKGROUND: Numerous therapeutic trials aimed at eradicating Helicobacter pylori (HP) from the gastric mucosa and preventing ulcer recurrence have been carried out; however, an optimal treatment has not yet been established with carefully controlled randomized studies . OBJECTIVE: The aim of our study was to evaluate the efficacy of an association of omeprazole (OM) coupled with two antibiotics in the eradication of HP and prevention of duodenal ulcer (DU) recurrence . METHODS: One hundred and eighty three patients with active DU were randomized under double-blind conditions to receive either OM 20 mg for 4 wk plus amoxycillin 3 g daily and metronidazole 1 g daily during the 2nd and 3rd wk (91 patients, group A) or OM 20 mg for 4 wk plus matching placebo (92 patients, group B) . Endoscopy was performed before and at the end of the 4-wk treatment as well as 2, 6, and 12 months later . Biopsies were taken from the duodenum, antrum, and gastric body at each endoscopic examination for HP histological detection and for evaluation of inflammatory changes according to the Sydney system . RESULTS: After 4 wk, 84/86 patients (98%) of group A and 80/86 (93%) of group B were healed of their ulcers . The percentage of eradication was 90% in group A and 1% in group B . During a 12-month follow-up, DU relapsed in 4/63 (6%, including two of three reinfected cases) HP-eradicated group A patients, 4/8 (50%) HP-noneradicated group A patients, and 52/65 (80%) persistently HP-positive group B patients . Rapid, complete, and persistent suppression of gastroduodenitis activity and gastric surface epithelium lesions was observed in most HP-eradicated group A patients, whereas a transient decrease of bacterial colonization and inflammatory scores in the antrum and a transient worsening of corpus gastritis were found in group B patients . CONCLUSIONS: The combined therapy with amoxycillin, metronidazole, and omeprazole is highly effective in both HP eradication and prevention of duodenal ulcer recurrence.

Arch Pediatr Adolesc Med, 1996 Apr, 150(4), 396 - 9
Therapy for acute otitis media . Preference of parents for oral or parenteral antibiotic; Bauchner H et al.; OBJECTIVE: To determine if parents prefer single-dose intramuscular (IM) therapy or standard 10-day oral therapy for treatment of acute otitis media (AOM) . DESIGN: Parents were asked their preference at the time their child was enrolled in a randomized controlled trial comparing the clinical efficacy of single-dose IM ceftriaxone sodium with 10 days of oral amoxicillin and clavulanate potassium for AOM . Additional information was collected at days 3 to 5 and 14 to 16 after the initiation of the therapy . SETTING: Primarily private practices; 15 sites . PATIENTS: For this study, 648 children aged 3 months to 6 years were randomly assigned to receive IM (n=327) or oral (n=321) therapy . RESULTS: The groups were equivalent in all measured sociodemographic factors . At the time of enrollment, 85% of parents expressed a preference for single-dose IM therapy . At days 3 to 5, no differences were reported in days children were absent from school or day care, parental absence from work, or loss of sleep by children . However, more parents with children in the IM therapy group than in the oral therapy group reported loss of sleep by the parent (35% vs 26%, P=.02, chi(2)) . At days 14 to 16, more parents with children in the IM group reported being "very satisfied" with the antibiotic (65%) compared with parents whose children were assigned to the oral therapy group (38%, P<.001) . In comparing current therapy to past oral therapy for AOM, 71% of the parents with children in the IM therapy group reported more satisfaction with current therapy, in contrast to 21% of parents with children in the oral therapy group (P<.001) . Of the parents, 83% indicated they would prefer single-dose IM therapy for AOM in the future . CONCLUSION: All of the parents prefer single-dose IM therapy for AOM over standard 10-day oral therapy.

Ann Hematol, 1996 Apr, 72(4), 273 - 9
Antibiotic strategy after the empiric phase in patients treated for a hematological malignancy; De Pauw BE et al.; Empiric broad-spectrum antibiotic therapy has become a generally accepted strategy in the treatment of febrile neutropenic patients . Particularly in patients with prolonged neutropenia, subsequent adaptation of such a regimen will be the rule rather than exception . Since there are no uniformly accepted guidelines for the modification of antibiotic therapy during the post-empiric phase, we assessed the impact of a set of rules that evolved during the first randomized trials . Evaluation of the clinician's compliance with these rules in 1951 febrile neutropenic episodes was the subject of the present analysis . Treatment was modified in 761 (39%) cases, and these changes were made according to the rules in 76% . For 75% of the alterations in treatment during the evening and night shifts, no reasonable explanation was established, while 93% of the modifications during the normal working hours were made for objective reasons . The empiric regimen was more frequently changed in patients with a clinical focus of infection at the onset of fever than in patients who showed fever as the only symptom of a possible infection . The perceived need for modification amounted to 69% in pulmonary infections, to 51% in skin and soft-tissue infections, to 44% in patients with abdominal complaints, and to 37% in upper respiratory tract infections . Glycopeptides constituted 22% of modifications, particularly in patients with a central venous catheter, and systemically active antifungals were administered in 16% of cases . Especially inexperienced clinicians tend to adjust antibiotic therapy, in spite of the fact that persistence of fever alone seldom reflects inadequate treatment when the clinical condition of the patient is stable or improving . On the other hand, the development of subsequent infectious events emphasizes that a genuine need for modification does frequently exist.

Am J Surg, 1996 Apr, 171(4), 394 - 8
Continuous regional arterial infusion of protease inhibitor and antibiotics in acute necrotizing pancreatitis; Takeda K et al.; PURPOSE: This study was conducted to determine whether continuous regional arterial infusion (CRAI) of the protease inhibitor, nafamostat mesylate, in acute necrotizing pancreatitis, would reduce mortality . In addition, the effectiveness of CRAI of the antibiotic imipenem in combination with nafamostat was investigated for its effect in preventing secondary infection of the pancreatic necrotic tissue . PATIENTS AND METHODS: Fifty- three patients with acute necrotizing pancreatitis were divided into three groups: Group I, 16 patients who were referred >8 days after disease onset, received intravenous nafamostat and antibiotics; Group II, 22 patients referred within 7 days, received nafamostat via CRAI, and antibiotics intravenously; Group III, 15 patients referred within 7 days, received both nafamostat and imipenem via CRAI . RESULTS: The mortality rates in Group II (13.6%) and group III (6.7%) were significantly reduced, as compared with that in group I (43.8%) . The incidence of infection of pancreatic necrosis in group III (0%) was significantly lower than those in group I (50%) and in group II (22.8%) . CONCLUSION: CRAI of nafamostat and imipenem in acute necrotizing pancreatitis was effective in reducing mortality and preventing the development of pancreatic infection.

Nat Med, 1996 Apr, 2(4), 467 - 9
Aminoglycoside antibiotics restore CFTR function by overcoming premature stop mutations; Howard M et al.; Cystic fibrosis (CF) is caused by mutations in the gene encoding the CF transmembrane conductance regulator (CFTR) . A single recessive mutation, the deletion of phenylalanine 508 (deltaF508), causes severe CF and resides on 70% of mutant chromosomes . Severe CF is also caused by premature stop mutations, which are found on 5% of CF chromosomes . Here we report that two common, disease-associated stop mutations can be suppressed by treating cells with low doses of the aminoglycoside antibiotic G-418 . Aminoglycoside treatment resulted in the expression of full-length CFTR and restored its cyclic AMP-activated chloride channel activity . Another aminoglycoside, gentamicin, also promoted the expression of full-length CFTR . These results suggest that treatment with aminoglycosides may provide a means of restoring CFTR function in patients with this class of mutation.

Ned Tijdschr Geneeskd, 1996 Mar 30, 140(13), 709 - 13
{Dog bites: publications on risk factors, infections, antibiotics and primary wound closure}; de Melker HE et al.; OBJECTIVE . To determine, on the basis of published research on dog bites, risk groups and localisations, risk factors for wound infection, effectiveness of prophylactic antibiotics and indications and contraindications for primary closure of the bite wounds . DESIGN . Literature study . METHODS . Search in Medline (1975-October 1994) on "dog" and "bite(s)" and selection using methodological inclusion and exclusion criteria . RESULTS . Incidence of dog bites is highest in younger children and in hands/arms . The infection rate amounts to 3-17% . Risk factors for wound infection include hand/arms, puncture wounds, delay of presentation and possibly older age . The effectiveness of prophylactic antibiotics appears to be limited . There is no evidence that the infection rate after primary closure of wounds is higher . Cleaning and debridement are important . CONCLUSIONS . More attention should be paid to prevention of dog bites, especially in children . Most important is adequate cleaning of the wounds . Antibiotics should be given on indication only, such as hand wounds, puncture deep wounds and immune compromised patients . Primary closure is not contraindicated.

Chem Phys Lipids, 1996 Mar 29, 79(2), 123 - 35
Aminoglycoside antibiotics prevent the formation of non-bilayer structures in negatively-charged membranes . Comparative studies using fusogenic (bis(beta-diethylaminoethylether)hexestrol) and aggregating (spermine) agents; van Bambeke F et al.; Aminoglycoside antibiotics cause aggregation but not fusion of negatively-charged liposomes at an extent proportional to their capacity to interact with acidic phospholipids (Van Bambeke et al., 1995, Eur . J . Pharmacol., 289, 321-333) . To understand why aggregation is not followed by fusion, we have examined here the influence of two aminoglycosides with markedly different toxic potential (gentamicin > isepamicin) on lipid phase transition in negatively-charged liposomes using 31P-NMR spectroscopy, in comparison with spermine (an aggregating agent) and bis(beta-diethylaminoethylether)hexestrol or DEH (a fusogenic cationic amphiphile) . Gentamicin, spermine, and, to a lesser extent, isepamicin inhibit the appearance of the isotropic signal seen upon warming of control liposomes and denoting the presence of mobile structures . This non-bilayer signal appeared most prominently when liposomes were incubated with DEH, a strong fusogenic agent . We conclude that aminoglycosides, like spermine, have the potential to prevent membrane fusion, by inhibiting the development of a critical change in membrane organization, which is associated with fusion . We suggest that this capacity could be a determinant in aminoglycoside toxicity.

Chem Biol Interact, 1996 Mar 25, 100(2), 165 - 76
Comparison of DNA sequence selectivity of anthracycline antibiotics and their 3'-hydroxylated analogs; Jolles B et al.; The sequence selectivity of three anthracyclines and their 3' hydroxylated analogs (in which an OH replaces NH3+ in the daunosamine at neutral pH) was examined in DNase I footprinting experiments on a 158-bp DNA fragment . We found that chemical modification of the daunosamine at C3' has more drastic consequences for sequence selectivity than chemical modification at C4 and C14 of the aglycone moiety . All anthracyclines and hydroxylated derivatives selectively recognize the triplet PyAPy . The importance of NH3+ in stabilizing the interaction was evidenced . First of all, comparable protection patterns require 5 times more hydroxyanthracycline than regular anthracycline . Furthermore, it is only after the replacement of NH3+ by OH that an additional protection site - CGC--appears . GGC is the site of best selectivity of the hydroxyanthracyclines . Anthracyclines can be considered both intercalators (aglycone moiety) and minor groove binders (sugar moiety) . Since intercalating drugs show a slight preference for GC base pairs, we suggest hydroxylated anthracyclines to have a sequence specificity closer that of pure intercalators . Chemical modifications at C4 and C14 only modify the hydrogen bonding stabilization of the DNA-aglycone moiety complex: the more the anthracycline or its analog is lipophilic, the less it will interact with the sugar-phosphate chain.

Tidsskr Nor Laegeforen, 1996 Mar 10, 116(7), 837 - 40
{May the choice of antibiotics against gonorrhea be guided by anamnesis?}; Aavitsland P; Aminopenicillin with probenecid is the standard treatment for gonorrhoea in Norway . Nowadays, one fourth of the cases are caused by gonococci that produce betalactamase . Clinicians who have to treat gonorrhoea at the time of first presentation, while awaiting sensitivity testing in the laboratory, are reluctant to use non-standard treatment except when indicated . Is it possible to predict, on the basis of the patient history, which cases need non-standard treatment? A logistic model was fitted to data on a random half of cases of gonorrhoea reported in 1993 and 1994, and validated in the other half of the cases . Infection with betalactamase-producing strains was associated with patients born in Africa or Asia, with patients who had acquired the infection in these areas, and with residence in the Oslo area . Presence of at least one of these factors predicted 87% of the resistant cases, but 54% of patients would have received non-standard treatment . Thus, all patients might as well receive treatment that cures betalactamase-producing strains.

J Chromatogr B Biomed Appl, 1996 Mar 3, 677(2), 275 - 90
Capillary high-performance liquid chromatography-fast atom bombardment mass spectrometry of 24 cephem antibiotics; Kobayashi K et al.; Using capillary high-performance liquid chromatography (HPLC)-fast atom bombardment (FAB) mass spectrometry (MS), both positive and negative FAB mass spectra of 24 cephem antibiotics with diethanolamine (DEA) and glycerol (GLY) as matrices are presented . In the positive mode, an internal quasi-molecular peak together with relatively abundant fragment peaks were obtained from all 24 drugs with both matrices, though DEA provided more information on molecular mass of a compound than did GLY for some drugs . In the negative mode, the background was generally lower than that in the positive, but neither the quasi-molecular nor molecular peak was detected in several drugs with either matrix . The drugs were isolated from serum samples using an octadecyl reversed-phase cartridge; recoveries were generally over 60%, With this isolation and the capillary HPLC-FAB-MS in the positive mode, ceftriaxone and cefazolin, two of the most popular cephem antibiotics, were successfully identified in 0.5 ml of sera obtained from a clinical or an autopsy case.

Antibiot Khimioter, 1996 Mar, 41(3), 40 - 3
{Rational use of antibiotics--basis for prevention of their side effects}; Gurin NG et al.; Three hundred and sixty eight case histories of pulmonological patients and 127 case histories of other patients were examined retrospectively . Morphohistochemical investigation of the internal ear structure was performed on rabbits treated with different aminoglycoside antibiotics in various doses . Within 15 years (from 1978 to 1992) the incidence of adverse reactions to the antibiotic therapy in the pulmonological patients decreased from 33 to 5 per cent as a result first of all of the observation of the principles of antibiotic therapy by the physicians . Within 1992-1994 there were recorded no classical complications of the antibiotic therapy in the pulmonological patients . The only adverse reaction was the body temperature elevation . In 1994 there was stated the drug fever in 37 patients, 35 of them being treated without observation of the principles of rational antibiotic therapy . The aminoglycosides were used for the treatment of the main and concomitant diseases in 51 and 22 per cent of the patients respectively . Prophylactically the aminoglycosides were used in 12 per cent of the patients . In 15 per cent of the cases the use of the antibiotics was not indicated . The application of the routine methods for the control of the safe use of the aminoglycosides was stated to be unsatisfactory which made it impossible to detect nephrological complications . Nevertheless, changes for the worse were recorded twice as often as those for the better . The development of iatrogenic neuritis of the acoustic nerve to some extent associated with the incorrect regimens of the aminoglycoside therapy was stated in 3.9 per cent of the patients.

Antibiot Khimioter, 1996 Mar, 41(3), 15 - 9
{Use of hydrogen peroxide in the treatment of sewage in antibiotic production}; Polunina EE et al.; The possible use of hydrogen peroxide as an oxidant in the local treatment of the sewage in antibiotic production was investigated . The data on oxidation of SASs and other pollutants in antibiotic production by hydrogen peroxide alone or in the presence of ferrous sulfate as a homogenous catalyst are presented . The influence of the sewage preliminary treatment by hydrogen peroxide on the foaming was studied . It was shown advisable to use the described process for the local treatment as the first stage followed by the sewage electrochemical treatment.

J AOAC Int, 1996 Mar-Apr, 79(2), 397 - 404
Multiresidue method for confirmation of macrolide antibiotics in bovine muscle by liquid chromatography/mass spectrometry; Delepine B et al.; A particle beam/liquid chromatographic/mass spectrometric (PB/LC/MS) method capable of determining 5 macrolides in bovine muscle is described . Spiramycin, tylosin, tilmicosin, erythromycin, and josamycin residues in bovine muscle are confirmed by reversed-phase LC/MS incorporating gradient elution . Macrolides are extracted from tissue with chloroform, and the extract is purified with a diol solid-phase extraction cleanup . The 5 macrolides are identified by negative and positive chemical ionization with selective ion monitoring of 2 ions in each mode . The procedure confirms the presence of each macrolide at 50 micrograms/kg in spiked samples.

J Gen Physiol, 1996 Mar, 107(3), 433 - 43
Subconductance block of single mechanosensitive ion channels in skeletal muscle fibers by aminoglycoside antibiotics; Winegar BD et al.; The activity of single mechanosensitive channels was recorded from cell-attached patches on acutely isolated skeletal muscle fibers from the mouse . The experiments were designed to investigate the mechanism of channel block produced by externally applied aminoglycoside antibiotics . Neomycin and other aminoglycosides reduced the amplitude of the single-channel current at negative membrane potentials . The block was concentration-dependent, with a half-maximal concentration of approximately 200 microM . At high drug concentrations, however, block was incomplete with roughly one third of the current remaining unblocked . Neomycin also caused the channel to fluctuate between the open state and a subconductance level that was also roughly one third the amplitude of the fully open level . An analysis of the kinetics of the subconductance fluctuations was consistent with a bimolecular reaction between an aminoglycoside molecule and the open channel (kon = approximately 1 x 10(6) M-1s-1 and koff = approximately 400 s-1 at -60 mV) . Increasing the external pH reduced both the rapid block of the open channel and the frequency of the subconductance fluctuations, as if both blocking actions were produced by a single active drug species with a pKa = approximately 7.5 . The results are interpreted in terms of a mechanism in which an aminoglycoside molecule partially occludes ion flow through the channel pore.

J Gen Physiol, 1996 Mar, 107(3), 421 - 32
Block of single L-type Ca2+ channels in skeletal muscle fibers by aminoglycoside antibiotics; Haws CM et al.; The activity of single L-type Ca2+ channels was recorded from cell-attached patches on acutely isolated skeletal muscle fibers from the mouse . The experiments were concerned with the mechanism by which aminoglycoside antibiotics inhibit ion flow through the channel . Aminoglycosides produced discrete fluctuations in the single-channel current when added to the external solution . The blocking kinetics could be described as a simple bimolecular reaction between an aminoglycoside molecule and the open channel . The blocking rate was found to be increased when either the membrane potential was made more negative or the concentration of external permeant ion was reduced . Both of these effects are consistent with a blocking site that is located within the channel pore . Other features of block, however, were incompatible with a simple pore blocking mechanism . Hyperpolarization enhanced the rate of unblocking, even though an aminoglycoside molecule must dissociate from its binding site in the channel toward the external solution against the membrane field . Raising the external permeant ion concentration also enhanced the rate of unblocking . This latter finding suggests that aminglycoside affinity is modified by repulsive interactions that arise when the pore is simultaneously occupied by a permeant ion and an aminoglycoside molecule.

Br J Clin Pharmacol, 1996 Mar, 41(3), 229 - 34
Hospital antibiotic prescribing successfully modified by 'immediate concurrent feedback'; Seto WH et al.; 1 . To determine the effectiveness of ongoing immediate concurrent feedback (ICF) in minimizing 'inappropriate' sultamicillin or co-amoxiclav prescribing via the parenteral route (i.e . when the oral route was accessible and not contraindicated), a prospective controlled audit was carried out on hospital inpatients over a 20 month period . 2 . After an education programme to promote oral rather than unnecessary intravenous (i.v.) use of sultamicillin, co-amoxiclav and certain other drugs, an ongoing ICF strategy was instituted . 3 . ICF entailed issue of memos on the following day to prescribers of i.v . sultamicillin or co-amoxiclav for inpatients in whom this route was deemed 'inappropriate', by a specially trained nurse using strict objective criteria . The memos recommended oral prescribing (particularly of co-amoxiclav, currently the less expensive alternative) . 4 . After starting ICF, there were consistent, clinically and statistically significant reductions in the monthly proportions of (i) admissions prescribed i.v . sultamicillin or co-amoxiclav (38% P < 0.001), (ii) those in whom the route was 'inappropriate' (75%, P < 0.001), and (iii) corresponding ratios of i.v./oral usage and expenditure, oral sultamicillin/co-amoxiclav usage and expenditure, as well as total and per admission expenditure on i.v . forms (> or = 43%, P < 0.01) . 5 . For i.v . cefuroxime (for which there was no ICF) and its oral counterpart cefuroxime-axetil, there were no comparable changes in usage or expenditure . 6 . This simple, ongoing ICF strategy was effective and well accepted; estimated net monthly savings being HK$26-30,000.

J Am Pharm Assoc (Wash), 1996 Mar, NS36(3), 206 - 9
Extemporaneous preparation of antibiotic ophthalmic solutions; Hammond RW et al.; Until the introduction of ocular ciprofloxacin, the standard of practice in treating bacterial corneal ulcers required topical antibiotic ophthalmic solutions that were either not commercially available or not available in the higher concentrations needed . A survey was mailed to 125 hospital pharmacies and 125 community pharmacies in Oklahoma to determine the availability of extemporaneously prepared antibiotic ophthalmic solutions . Of 72 hospital pharmacies and 60 community pharmacies that responded, 17 hospital and 2 community pharmacies reported that they do compound these solutions . The main reasons given by the other pharmacies for not offering this service were the lack of a laminar flow hood or other equipment and lack of an aseptic environment . If extemporaneously prepared antibiotic ophthalmic solutions are needed to treat corneal ulcers, then pharmacists have a responsibility to prepare them . The recent publication of a handbook providing formulations for those products and the "ASHP Technical Assistance Bulletin on Pharmacy-Prepared Ophthalmic Products" may encourage more pharmacies to provide this needed service.

Acta Pharm Hung, 1996 Mar, 66(2), 89 - 94
Analytical investigation of beta-lactam antibiotics in pharmaceutical preparations . IX . Colorimetric determination of six cephalosporins of second and third generation in the range of micromolar concentrations; Issopoulos PB et al.; A sensitive, accurate, precise and the same time simple and rapid method for the colorimetric determination of some cephalosporins of the second and third generations, such as: cefoxitin sodium (CFXT), cefaclor (CFCL), cefamandole nafate (CFMD), ceforanide l-lysine (CFRN), cefotaxime sodium (CFTX), and cefurozime sodium (CFRX) was described . The new method proposed is based: a) On the reduction of Fe(III) to Fe(II) by the drug analysed and b) On complexation of Fe(II) formed with o-Phenanthroline (O-Phen) consistently the formation of the well known highly stable orange-red coloured chelate complex {Fe(II)-(o-Phen)3}2+ which exhibits an absorption maximum at lambda = 510 nm (pH 4.50 +/- 0.2) . Beer's law is obeyed for: 1.0 - 37.5 microgram mL-1 for CFX, 1.0 - 25.0 microgram mL-1 for CFMD, CFRN, and CFTX and 2.0 - 37.5 microgram mL-1 for CFTX and CFCL, while the apparent molar absorptivity ( epsilon in L mol-1cm-1) and the Sandell's sensitivity in (ngcm-2) both referred to the drug analyzed, are 1.29 x 10(4); 34.7 (CFXT), 7.61 x 10(3); 50.7 (CFCL), 3.33 x 10(4); 15.4 (CFMD), 2.60 x 10(4); 17.6 (CFRN) respectively . The regression line equation for each one of the above studied cephalosporins were calculated with a correlation coefficient 0.9997 < r < 1.0000; the accuracy and the precision of the method was considered as very satisfactory, while the results of a statistical analysis by means of the Student's t-test and the variance ratio F-test prove that no significant difference was observed between the results of the proposed method and those of official one.

J Virol, 1996 Mar, 70(3), 1527 - 34
Inhibition of Nef- and phorbol ester-induced CD4 degradation by macrolide antibiotics; Luo T et al.; Human immunodeficiency virus type 1 (HIV-1) is the causative agent of AIDS . The simian immunodeficiency virus (SIV) causes a similar syndrome in macaques . The product of the nef gene of SIV has been shown to be important for virus replication and disease progression in vivo . In vitro, both SIV and HIV Nef downregulate surface expression of CD4 and accelerate total CD4 turnover . The mechanism by which Nef downregulates CD4 has not been established . A current model suggests that Nef enhances cell surface CD4 endocytosis and degradation in lysosomes . However, this was recently challenged when CD4 was found to accumulate in early endosomes of cells expressing Nef . Because inhibition of Nef function might halt virus replication and disease progression, we tested two macrolide antibiotics for their ability to inhibit Nef function . Concanamycin B (ConB) and bafilomycin A1 (BFLA1) are specific inhibitors of acidification of cell endosomes and lysosomes and, unlike other inhibitors, do not affect transport . Although ConB (25 nM) and BFLA1 (100 nM) blocked phorbol myristate acetate- and Nef-induced CD4 degradation in human monocyte U937 cells, CD4 surface expression was not recovered . Instead, CD4 accumulated in lysosomes . To determine if Nef is directly responsible for CD4 degradation or if they bind to each other in a manner similar to Vpu, transcripts of human CD4 and HIV-1 nef were cotranslated in vitro . Our results indicate that under our experimental conditions, Nef does not affect CD4 stability and does not associate with CD4 in this in vitro system . Our data suggest that (i) CD4 downregulation by Nef results in degradation of CD4 in lysosomes, (ii) inhibition of CD4 degradation by macrolide antibiotics does not restore surface expression, and (iii) the inhibition of CD4 expression by Nef appears to be indirect and is likely to involve cellular factors.

J Antibiot (Tokyo), 1996 Mar, 49(3), 299 - 311
Himastatin, a new antitumor antibiotic from Streptomyces hygroscopicus . III . Structural elucidation; Leet JE et al.; The structure of the antitumor antibiotic himastatin was determined using a combination of spectroscopic and chemical degradation techniques . Himastatin is a unique dimeric cyclohexadepsipeptide joined through a biphenyl linkage between two oxidized tryptophan units . The gross structure of the dimer was established through degradative ozonolysis . Himastatin consists of D-valine, D-threonine, L-leucine, L-alpha-hydroxyisovaleric acid, (3R,5R)-5-hydroxypiperazic acid, and (2R,3aR,8aR)-3a-hydroxyhexahydropyrrolo{2,3b}indole 2-carboxylic acid subunits.

J Antibiot (Tokyo), 1996 Mar, 49(3), 249 - 52
Studies on cochleamycins, novel antitumor antibiotics . III . Biosyntheses of cochleamycins: incorporation of 13C- and 2H-labeled compounds into cochleamycins; Shindo K et al.; Biosynthetic studies using 13C- and 2H-labeled compounds revealed that the carbon skeletons of cochleamycins A and B were derived from eight acetic acid units and one propionic acid unit with the introduction of an acetoxy group at C-10, which was replaced by an isobutyryl residue derived from valine in cochleamycins A2 and B2.

J Antibiot (Tokyo), 1996 Mar, 49(3), 244 - 8
Studies on cochleamycins, novel antitumor antibiotics . II . Physico-chemical properties and structure determination; Shindo K et al.; The structure of cochleamycins A, A2, B and B2 (Fig . 1), novel antitumor antibiotics, were elucidated by NMR spectral analysis . Cochleamycins were found to possess novel carbocyclic skeletons.

J Antibiot (Tokyo), 1996 Mar, 49(3), 241 - 3
Studies on cochleamycins, novel antitumor antibiotics . I . Taxonomy, production, isolation and biological activities; Shindo K et al.; Novel antitumor antibiotics cochleamycins A, A2, B and B2 (Fig . 1) were isolated from the culture broth of Streptomyces sp . DT136 . They were purified by column chromatography on silica gel, reversed phase HPLC and then isolated as colorless powder . Cochleamycins showed growth inhibition against tumor cells in vitro.

Biochemistry, 1996 Feb 20, 35(7), 2047 - 53
Parsing the free energy of anthracycline antibiotic binding to DNA; Chaires JB et al.; The DNA binding free energy of eight anthracycline antibiotics was determined as a function of NaCl concentration . Compounds were chosen for study that differed from the parent compounds, doxorubicin or daunorubicin, at a single chemical substituent . Determination of the salt concentration dependence of the binding constant allowed us to dissect the DNA binding free energy of each compound into its component nonelectrostatic and polyelectrolyte contributions . Comparison of the nonelectrostatic free energy contribution allowed us to evaluate the net energetic contribution of specific functional groups to DNA binding . These quantitative data revealed a surprisingly large and favorable energetic contribution (2 kcal (mol-1)) of the groove-binding daunosamine moiety and a substantial energetic penalty for alteration of its stereochemistry . The energetic cost of removal of hydroxyl groups at the C-9 and C-14 positions (which structural studies indicate may participate in hydrogen-bonding interactions with the DNA) was approximately 1 kcal mol(-1) . Replacement of the 3'-amino group with a hydroxyl group led to a loss of 0.7 kcal mol(-1) in binding free energy, above and beyond the energetic penalty resulting from the removal of its positive charge from the antibiotic . The results and analysis presented here provide a rigorous and detailed description of structure-DNA affinity relationships among anthracycline antibiotics . The results are of general interest in understanding how total ligand binding free energies are partitioned among substituents and will be useful in the formulation of rules for the rational design of novel DNA binding agents.

Biochem Biophys Res Commun, 1996 Feb 15, 219(2), 580 - 3
Purification and characterization of two haloperoxidases from the glycopeptide antibiotic producer Streptomyces toyocaensis NRRL 15009; Marshall GC et al.; Streptomyces toyocaensis NRRL 15009 produces A47934, a glycopeptide antibiotic . This compound is composed of several unusual amino acids, some of which have chlorinated aromatic rings . We have isolated two distinct halogenating enzymes, a chloroperoxidase (42,882 Da) and a catalase/bromoperoxidase (53,890 Da), from late log phase drug producing cultures of this organism grown on soy based media . Both these enzymes are azide sensitive and show absorption spectra consistent with the presence of an iron-heme group . We have characterized these enzymes with respect to substrate specificity, steady state kinetics, molecular mass and N-terminal sequence . The catalase/bromoperoxidase is similar to an enzyme from the chloramphenicol producer, Streptomyces venezuelae, while the chloroperoxidase is a unique protein.

Electrophoresis, 1996 Feb, 17(2), 359 - 66
Analysis of macrolide antibiotics by capillary electrophoresis; Flurer CL; Capillary electrophoresis was utilized in the study of the macrolide antibiotics (i.e . pharmaceutical glycoconjugates) clarithromycin, erythromycin, oleandomycin, troleandomycin, and spiramycin . In order to assist in analyte solubilization, two buffer systems using acetonitrile were developed . The first system involved 30 mM sodium cholate and 20% acetonitrile in 80 mM sodium phosphate, pH 6 . This buffer permitted the baseline resolution of all five glycoconjugated antibiotics . In addition, erythromycin was separated from its derivatives estolate and ethylsuccinate . In the absence of surfactants, a higher acetonitrile quantity, 65%, was used in the second buffer system, with 35 mM sodium phosphate, pH 6 . Selectivity between oleandomycin and clarithromycin was reversed in this system compared to the cholate buffer, indicating solute interaction with the cholate micelles in the previous system . Calibration linearity and detection sensitivity were improved in the high acetonitrile buffer, due to decreased background absorbance . It was demonstrated that both buffer systems can be utilized for the visualization of minor components that may be present in bulk pharmaceuticals.

J Biochem (Tokyo), 1996 Feb, 119(2), 274 - 80
Uncoupling mechanism of glycoside antibiotic aculeximycin in isolated rat-liver mitochondria; Miyoshi H et al.; Effects of basic glycoside antibiotic aculeximycin (ACM) on the oxidative phosphorylation of rat-liver mitochondria were examined . ACM was shown to be a potent uncoupler of the oxidative phosphorylation . To cause the same extent of respiration release, higher concentration of ACM was required in phosphate (Pi)-free medium than in Pi medium . During the uncoupling caused by ACM in Pi medium, large amplitude swelling and oxidation of intramitochondrial NAD(P)H occurred, indicating that ACM remarkably enhances permeability of the inner mitochondrial membrane . The Pi uptake via Pi/H+ symporter was shown to play an important, but not essential, role in the uncoupling by ACM, indicating the increase in membrane permeability is mostly due to acceleration of Pi/H+ influx through Pi/H+ symporter activated by ACM . ACM is the first naturally occurring antibiotic, to our knowledge, which activates Pi/H+ symporter . However, since the inhibition of Pi/H+ symporter by N-ethylmaleimide did not completely abolish the uncoupling activity of ACM, and ACM induced the uncoupling even in Pi-free medium, an increase in the membrane permeability for other ions, such as Na+ and K+, due to a different action mechanism has also to be considered . On the other hand, positively charged amine local anesthetics, like dibucaine, prevented the uncoupling activity by ACM in both Pi and Pi-free medium . The uncoupling activity of N-diacetylated ACM lacking free amino groups was ca . 1/120th that of ACM, indicating that positively charged amino groups are important for the uncoupling activity . It is suggested that some specific interactions between positively charged amino groups of ACM and the binding site, which is probably negatively charged, are triggers that affect the permeability of the inner mitochondrial membrane . Amine local anesthetics may mask the negative charge of the binding site, thereby interfering with ACM binding.

Appl Microbiol Biotechnol, 1996 Feb, 44(6), 705 - 9
Unexpected enhancement of beta-lactam antibiotic formation in Streptomyces clavuligerus by very high concentrations of exogenous lysine; Fang A et al.; L-Lysine is known to stimulate production of beta-lactam antibiotics by Streptomyces clavuligerus via provision of the lysine breakdown product, L-alpha-aminoadipic acid, which is a limiting precursor . Previous investigations utilized levels of 10-20 mM L-lysine as an addition to chemically-defined media resulting in 50-100% improvement in antibiotic production . We were surprised to note that as the concentration was further increased, the organism responded by producing even higher titers of antibiotics . The optimum concentration of 100 mM L-lysine yielded an approximate 500% increase in production with only minor effects on growth . DL- and D-Lysine also exerted enhancements suggesting the presence of a lysine racemase or some other route from D-lysine to L-alpha-aminoadipate in this organism; D-lysine was considerably less potent than DL- or L-lysine.

Bioorg Med Chem, 1996 Feb, 4(2), 151 - 63
Theoretical study of anthracycline antibiotic analogues--III . Conformational analysis on different 2, 6-dideoxy-2-halo-alpha-l-hexopyranoses by molecular mechanics and semiempirical methods; el Bergmi R et al.; Conformational analysis of 2,6-dideoxy-2-halo-alpha-L-hexopyranoses (compounds 1-11) has been performed by molecular mechanics and molecular orbital calculations including solvation effects . The numerical results obtained and those obtained from the electrostatic potential calculation have been used together to interpret theoretically the influence of the introduction of the halogen atom at the C-2 position of the sugar moiety.

Pathol Biol (Paris), 1996 Feb, 44(2), 113 - 23
{Bacteria, multiresistant to antibiotics, in intensive care units: epidemiological context and strategies of control}; Regnier B; In France, many hospitals have reported high prevalence of multiply resistant strains, mostly in intensive care units . However, resistance has spred to other medical or surgical wards, and to rehabilitation or long term care facilities as well . Both antibiotic misure and cross-colonization via tronsient carriage on bouds of caregivers account for these epidemics . In turn, high prevalence of resistance leads to increased antibiotic prescriting which results in extra costs and further emergence of new resistance mechanisms . In addition, such high prevalence might well contribute to increased morbidity and extra-incidence of nosocomial infections . Control of resistant strains requires proper use of antibiotics and prevention of cross-colonization, which relies on identification of reservoirs and effective implementation of isolation precautions.

Arzneimittelforschung, 1996 Feb, 46(2), 213 - 7
Influence of the antibiotics erythromycin and azithromycin on the pharmacokinetics and pharmacodynamics of midazolam; Zimmermann T et al.; The pharmacokinetic and pharmacodynamic interaction between azithromycin (CAS 83905-01-5), an azalide antibiotic, and midazolam (CAS 59467-70-8), a short-acting hypnotic agent, was investigated in an open, three-way cross-over study, including erythromycin (CAS 114-07-8) as a positive control . Twelve healthy male and female subjects had standard doses of azithromycin (500 mg o.d . over 3 days), or erythromycin (500 mg t.i.d . over 5 days), or no pretreatment . On the day of the last dose, they ingested 15 mg midazolam . Blood samples were collected and psychometric tests performed . Erythromycin pretreatment (E) significantly changed the pharmacokinetics of midazolam compared to control (C), whereas azithromycin (A) had no such effect . The parameters are summarized as follows: area under the concentration-time curve, AUC (C) 173.8 h.ng.ml-1 vs . (E) 662.7 h.ng.ml-1*+ and (A) 220.0 h.ng.ml-1; concentration maxima (C) 67.2 ng.ml-1 vs . (E) 182.3 ng.ml-1*+ and (A) 86.7 ng.ml-1; elimination half-life (C) 2.21 h vs . (E) 4.85 h* and (A) 2.41 h (* p < 0.05 vs . (C), +p < 0.05 vs . (A)) . Pharmacodynamic tests (digit symbol substitution test; critical flicker fusion test; subjective analog scale for rating of alertness; duration of sleep) consistently showed significant differences after erythromycin pretreatment compared to control, but not after azithromycin . Erythromycin, but not azithromycin, causes clinically significant changes in the pharmacokinetics and pharmacodynamics of midazolam.

Int J Epidemiol, 1996 Feb, 25(1), 204 - 9
Prevalence of antibiotics to hepatitis C in a population of intravenous drug users in Valencia, Spain, 1990-1992; Bolumar F et al.; BACKGROUND . Hepatitis C has been related to other viral diseases such as the human immunodeficiency virus infection (HIV) or hepatitis B (HBV) . The objective of this study was to estimate the prevalence and determinants of antibodies to hepatitis C virus (HCV) in intravenous drug users (IVDU) in Valencia (Spain) and to compare the seroprevalence between the HCV, HIV and HBV in this high risk group . METHODS . A cross-sectional study was conducted in a sample of 1056 current IVDU from the Valencia area who attended the city's AIDS Information Centre between January 1990 and December 1992 . Information on sociodemographic, sexual behaviour, and drug use variables was collected by means of a structured questionnaire . Antibodies to HCV, HIV and HBV were assayed by ELISA test . RESULTS . The seroprevalence of HCV for the whole period was 85.5% (95% confidence interval {CI}: 83.2-87.5%), ranging from 76.5% in 1990 (95% CI: 71.9-81.1%) to 87.8% in 1992 (95% CI: 82.5-93.1%) . Year of testing and prevalence of HBV markers showed an independent association with HCV seroprevalence . When only IVDU aged < 25 years were analysed, sharing of needles also appeared as an independent dominant . Of those IVDU with less than one year of addiction, 69% were HCV seropositive compared with 41% for HBV and 14% for HIV . CONCLUSIONS . Intravenous drug users in Valencia showed one of the highest reported hepatitis C seroprevalences (85.5%) . A more efficient parenteral transmission of hepatitis C virus than HBV or HIV is suggested.

J Antibiot (Tokyo), 1996 Feb, 49(2), 181 - 93
Dimerization of A82846B, vancomycin and ristocetin: influence on antibiotic complexation with cell wall model peptides; Linsdell H et al.; The thermodynamics of glycopeptide antibiotic dimerization have been studied by means of sedimentation equilibrium, using A82846B, vancomycin, ristocetin and complexes formed with several cell wall model peptides . These results indicate that vancomycin dimerization can be strongly promoted in two ways: i) stabilization of the antibiotic conformation in which the carbonyl group of residue three is on the back face of the molecule and ii) preferential interaction of the dimer with the lysine residue of N,N'-diacetyl-lysyl-D-alanyl-D-alanine . This effect was not found in ristocetin . A82846B forms stable dimers at very low antibiotic concentration . Two conformational forms have been found for complexed A82846B by 1H NMR . However, calorimetric binding experiments have shown that all its binding sites are thermodynamically equivalent . The affinity of the A82846B dimer for the tripeptide has been estimated to be about 3kJ x mol-1 higher than that of the vancomycin monomer and about -2.6kJ x mol-1 lower than that of dimeric vancomycin . The possible role of dimerization in the biological activity of glycopeptide antibiotics is discussed further on the basis of present thermodynamic data.

Biochim Biophys Acta, 1996 Jan 31, 1278(2), 223 - 32
Association of polyene antibiotics with sterol-free lipid membranes: I . Hydrophobic binding of filipin to dimyristoylphosphatidylcholine bilayers; Milhaud J et al.; The interaction of filipin III with multilamellar vesicles (MLV) of dimyristoylphosphatidylcholine (DMPC ) was studied by four complementary methods leading to the following results: (1) The modifications of the filipin dichroic spectrum, by adding preformed fluid DMPC MLV, provide evidence of a saturable association with the stoichiometry DMPC/filipin = 4.2 +/- 0.5, constant between 24 and 35 degrees Celsius . (2) Thermograms obtained by differential scanning calorimetry (DSC) on mixtures where filipin is incorporated during the formation of MLV exhibit a high-temperature tail the more marked the higher the filipin content and some structures at temperatures which depend on this content . The corresponding evolution with the temperature of the CD spectra reveals that the characteristic bound filipin spectrum appears at the temperature at which a structure emerges . (3) Titration calorimetry measurements reveal that the association process is exothermic in the temperature range of the DSC endotherms in agreement with the filipin-induced ordering of the lipid chains, previously established by 2H-NMR in the same temperature range (Milhaud et al.(1989) Eur . Biophys . J . 17, 151-158) . A discussion of the relevancy of this exothermicity to the hydrophobic effect is developed by referring to the paper by Wimley and White ((1993) Biochemistry 32, 6307-6312).

Ned Tijdschr Geneeskd, 1996 Jan 27, 140(4), 207 - 9
{Reversible tooth discoloration during oral use of antibiotics}; Meyboom RH et al.; From January 1991 until June 1995 . 25 cases were reported to the Netherlands Pharmacovigilance Foundation LAREB of yellow to brown tooth discoloration following the oral use of medication; 21 cases (84%) involved antibiotics, of which 14 were amoxicillin . 17/21 patients were children, with ages ranging from 1 to 10 years . All children used liquid formulations (suspension or solutabs) . Discoloration was reversible in all cases, but had a protracted course in some . Presumably a pigment precipitated on (and not in) the teeth, but the nature of the pigment was uncertain.

J Biol Chem, 1996 Jan 19, 271(3), 1579 - 90
The biosynthetic pathway of the aminonucleoside antibiotic puromycin, as deduced from the molecular analysis of the pur cluster of Streptomyces alboniger; Tercero JA et al.; The pur cluster which encodes the puromycin biosynthetic pathway from Streptomyces alboniger was subcloned as a 13-kilobase fragment in plasmid pIJ702 and expressed in an apparently regulated manner in the heterologous host Streptomyces lividans . The sequencing of a 9.1-kilobase DNA fragment completed the sequence of pur . This permitted identification of seven new open reading frames in the order: napH, pur7, pur10, pur6, pur4, pur5, and pur3 . The latter is followed by the known pac, dmpM, and pur8 genes . Nine open reading frames are transcribed rightward as a unit in opposite direction to that of the pur8 gene which is expressed as a monocistronic transcript from the right-most end . napH encodes the known N-acetylpuromycin N-acetylhydrolase . The deduced products from other open reading frames present similarities to: NTP pyrophosphohydrolases (pur7), several oxidoreductases (pur10), the putative LmbC protein of the lincomycin biosynthetic pathway from Streptomyces lincolnensis (pur6), S-adenosylmethionine-dependent methyltransferases (pur5), a variety of presumed aminotransferases (pur4), and several monophosphatases (pur3) . According to these similarities and to previous biochemical work, a puromycin biosynthetic pathway has been deduced . No cluster-associated regulatory gene was found . However, both pur10 and pur6 genes contain a TTA codon, which suggests that they are translationally controlled by the bldA gene product, a specific tRNA(Leu).

Curr Opin Ophthalmol, 1996 Feb, 7(1), 39 - 42
Perioperative antibiotic, steroidal, and nonsteroidal anti-inflammatory agents in cataract intraocular lens surgery; Abel R Jr et al.; Ophthalmologists are choosing topical antibiotics and corticosteroids more frequently than injectable agents for their current cataract surgical techniques . The preoperative use of povidone-iodine 5%, dilute intracameral antibiotics (via the balanced saline solution infusion), and postoperative impregnated collagen shields or soft contact lenses augment the therapeutic armamentarium . Nonsteroidal anti-inflammatory drugs, especially diclofenac 0.1%, have played an important role in decreasing postoperative convalescence through maintaining preoperative mydriasis, reducing anterior chamber reactions, and inhibiting cystoid macular edema . With fewer side effects, nonsteroidal anti-inflammatory drugs are minimizing the role of topical steroids.

Bull Soc Pathol Exot, 1996, 89(5), 350 - 2
{Use of antibiotics in pediatric surgery at the University Hospital Center at Yopougon, Abidjan (Ivory Coast)}; Aguehounde C et al.; Considering 901 files of in-patients (68% of boys and 32% of girls, mean of ages: 2 days to 16 years) and prescriptions at the hospital of Yopougon during a period of two years (1991-1992), the authors have made a retrospective and critical study of the use of antibiotics in this department . Antibiotics, either demanded by strong presumption of infection, either indicated as a prophylaxis, have been administered to 54% of the patients . When this antibiotic therapy has been curative (56% of the cases of first intention), it was considered correct in 97% of the cases . On the other hand, it was ill-done when it was a matter of antibioprophylaxis . An antibiotherapy of second intention has been prescribed when antibiotherapy of first intention had failed and also when the antibiotic reserve of the hospital was over . The average number of antibiotics given to a patient was 2.12, frequently associating aminoside and penicillin . The total cost of antibiotics was 78% of the whole drugs used to cure these patients and among them, the biggest cost was for cephalosporines of third generation.

Antibiot Khimioter, 1996, 41(11), 25 - 7
{Enhancement of treatment efficacy in experimental plague by the sequential administration of antibiotics}; Makarovskaia LN et al.; It was shown that the use of ampicillin, azlocillin or polymyxin 24 or 96 hours after the plague infection at the background of the every-day use of rifampicin in the doses protecting only 30 per cent of the animals from death provided 80-100-percent survival of the animals . With the every-day use of ampicillin, azlocillin or polymyxin in succession with rifampicin there was observed a 3-fold increases in the survival of the albino mice as compared to those exposed to an analogous dose of rifampicin alone . A decrease in the number of administrations of the above drugs and an increase in the intervals between the administration also resulted in a significant rise of the animal survival in comparison with that after the every-day use of a similar dose of rifampicin.

Pneumonol Alergol Pol, 1996, 64 Suppl 1, 63 - 9
{The influence of selected antibiotics on the central action of aminophyllines--experimental studies}; Szmygin K; Methylxanthines and some antibiotics can cause side effects, provoked by their central action, e.g . seizures . The epileptogenic effects of given drugs can be intensified during combined treatment, as a result of pharmacological interactions . In the present study the author investigated the influence of some commonly used antibiotics: benzylpenicillin, cefuroxime, doxycycline and amikacin upon central activity of methylxanthines in mice . The obtained results suggest, that all tested antibiotics, mainly benzylpenicillin, enhanced epileptogenicity of aminophylline in chemical seizures test . benzylpenicillin as only one among chosen antibiotics presented her own convulsant activity . During electrostimulation test, benzylpenicillin, doxycycline and amikacin intensified convulsions induced by methylxanthines . Only cefuroxime had no influence upon central action of methylxanthines in that experiments . Analysis of drugs' plasma levels, with using immunofluorescence methods, excluded pharmacokinetic interactions between them . Results of present investigation indicate, that there is a possibility of intensification of drugs' convulsant activity during combined treatment-aminophylline with some antibiotics in medical practice.

Mycopathologia, 1996, 135(3), 145 - 7
Role of Candida in indirect pathogenesis of antibiotic associated diarrhoea in infants; Ponnuvel KM et al.; One hundred and thirty seven isolates of Candida species were isolated from antibiotic associated diarrhoea cases and were examined to study the role of Candida in the pathogenesis of diarrhoea in infants . The quantitative estimation of yeast population by simple gram stain smear revealed more than 70% of the cases had 3+ score . The isolates further screened for detection of beta-lactamases . Among the isolated Candida sp, beta-lactamases was secreted by C . albicans, C . tropicalis, C . krusei and C . parapsilosis . Further, 46% of the Candida isolates were found to be produced 741-1110 mU/ml of beta-lactamases, suggesting that these enzyme would inactivate penicillin group of drugs and cause failure in the therapy directed against other diarrhoegenic bacteria.

Rocz Akad Med Bialymst, 1996, 41(2), 293 - 304
Synthetic analogues of netropsin and distamycin . III . Synthesis of a pyridine analogue of the pyrrolecarboxamide antitumour antibiotics; Bielawski K et al.; The synthesis of a new pyridine analogue of netropsin, N,N'-bis{6-(N-3-dimethylaminopropyl) carbamoylpyridin-2-yl} pyridine-2,5-dicarboxamide (VII) is described . The potential for use of VII as a carrier to place chemical functionalities into the minor groove of DNA which are capable of modifying DNA is discussed.

Ter Arkh, 1996, 68(8), 28 - 31
{Absolute diet therapy and antibiotic tolerance in bronchial asthma patients}; Fedoseev GB et al.; In 10 patients with bronchial asthma (BA) treated conventionally (control group), 10 BA patients on absolute diet therapy (group 1) and 10 BA patients in absolute diet therapy combined with wheat herb juice (group 2) tolerance to 12 antibiotics of different classes and some immunity factors were determined using a complex of diagnostic methods . The latter implies: case history, humoral and cell immunity defense system tests and special tests (chemical erythrograms and leukocyte migration inhibition test in plane capillary tubes with tested drugs) . The data obtained evidence for increased tolerance of the antibiotics in groups 1 and 2 as well as for changes in humoral defense system, especially in immunoglobulin E . The drug tolerance may be a therapeutic criterion of absolute diet therapy in bronchial asthma patients.

Bull World Health Organ, 1996, 74(5), 501 - 7
Standard management of acute respiratory infections in a children's hospital in Pakistan: impact on antibiotic use and case fatality; Qazi SA et al.; Acute respiratory infections (ARI) are a leading cause of childhood morbidity and mortality in Pakistan . The National ARI Control Programme was launched in 1989 in order to reduce the mortality attributed to pneumonia, and rationalize the use of drugs in the management of patients with ARI . WHO's standard ARI case management guidelines were adopted to achieve these objectives . The medical staff at the Children's Hospital, Islamabad, were trained in such management in early 1990; further training sessions were conducted when new staff arrived . Data on outpatients were obtained from special ARI abstract registers, which have been maintained in the outpatient department since January 1990 . Details on inpatients who were admitted with ARI were obtained from hospital registers . During the period 1989-92, the use of antibiotics in the outpatient department decreased from 54.6% to 22.9% (P < 0.0001) . The case fatality rate (CFR) in children admitted with ARI fell from 9.9% to 4.9% (P < 0.0001), while the overall case fatality rate fell from 8.7% to 6.2% . Our results from a tertiary health care facility show that standard ARI case management reduced both antibiotic use and expenditure on drugs . Although the ARI case management criteria, which are more sensitive than the conventional diagnostic criteria of auscultation and radiography, led to more admissions, we believe that this strategy contributed to a significant reduction in the ARI case fatality ratePIP: Acute respiratory infection (ARI) is the leading cause of death among children in Pakistan . The Government's National ARI Control Program seeks to reduce pneumonia-related mortality in children under 5 years, standardize clinical assessment, and rationalize the use of drugs in case management . To assess the impact of this protocol on ARI case fatalities and antibiotic use, the registries of ARI patients presenting to Children's Hospital in Islamabad in 1989-92 were reviewed . Staff training in ARI case management was initiated in 1990 . ARI admissions more than doubled from 776 in 1989 to 1673 in 1992 . Many children admitted in 1990-92 would not have been admitted if the 1989 criteria, based on clinical auscultation and radiologic diagnosis, had been followed . Use of antibiotics decreased significantly from 54.6% of ARI outpatient cases in 1989 to 30.2% in 1992 as a result of no longer providing medication to children with viral ARI . The case fatality rate for all hospital admissions decreased by 28% during the study period (from 8.7% in 1989 to 6.2% in 1992), while that for ARI decreased by 50.5% (from 9.9% to 4.9%) . The elimination of inappropriate antibiotic therapy associated with this protocol has the potential to save RS 39.8 million (US$1.2 million) from Pakistan's public health budget each year as well as to reduce both ARI and overall child mortality .

Rapid Commun Mass Spectrom, 1996, 10(13), 1615 - 20
Multiresidue determination of sulfonamide antibiotics in milk by short-column liquid chromatography coupled with electrospray ionization tandem mass spectrometry; Volmer DA; Liquid chromatography coupled to electrospray mass spectrometry and tandem mass spectrometry has been used for the determination and quantification of 21 sulfonamides and two potentiators (ormethoprim, trimethoprim) in milk . Separation using high-performance liquid chromatography was achieved in less than 6 min for all compounds on a short (4.0 x 50 mm, 3 micron) reversed-phase column . After sample clean-up, time-scheduled single-ion monitoring (SIM) yielded detection of sulfonamides in milk from low ppb level to the ppt level . The strategy used to detect, confirm and quantify sulfonamides in milk samples was as follows: (a) pre-screening (and cp3firmation) of target and non-target sulfonamides by precursor ion scan and/or multiple reaction monitoring experiments using generic product ions; (b) quantification of identified target compounds by monitoring their protonated molecule ions in a time-scheduled SIM experiment; (c) further confirmation, if necessary, by selected reaction monitoring using characteristic product ions.

J Basic Microbiol, 1996, 36(6), 383 - 7
Steroid transformation by mutants of Mycobacterium sp . with altered response to antibiotics; Barthakur S et al.; Mycobacterium sp . NRRLB3683 which is capable to convert beta-sitosterol to 1,4-androstadiene-3,17-dione (ADD) was treated with methyl methane sulfonate and two strains with altered sensitivity to various antibiotics were obtained . One of the strain was steroid 1(2)-dehydrogenase negative and the other positive . Efficiency of utilization of sterols followed the order beta-sitosterol > cholesterol > soluble cholesterol . The steroid 1(2)-dehydrogenase negative strain was capable of producing 17KS (AD) from beta-sitosterol and converting AD to testosterone and ADD to AD suggesting the negative role of 1(2)-dehydrogenase in sterol side chain cleavage and decrease in hydrogenase activity by mutation . But this enzyme can perform the reverse reaction under aerobic condition.

Chirurgie, 1996, 121(4), 298 - 308
{Tricalcium phosphate and gentamycin . In vitro and in vivo antibiotic diffusion, rehabilitation in bone site in sheep}; Prat-Poiret N et al.; Several different materials have been proposed as vectors to carry antibiotics to bone tissue . No material currently available satisfies all the prerequisites for the treatment of chronic osteitis with a simple procedure . The aim of this study was to assess the antibiotic releasing capacity of gentamycin-loaded beta tricalcium phosphate in vitro and in vivo in a sheep model . Experimental results showed that beta tricalcium phosphate can release a large percentage of its antibiotic load and that the kinetics of antibiotic release can be modulated by changing the volume and porosity of the blocks . This material is also well tolerated by the host and has the advantage of being porous and resorbable . Use of these properties would appear to be a major progress in the treatment of chronic bone infections.

J Ocul Pharmacol Ther, 1996 Spring, 12(1), 35 - 43
Using MTT viability assay to test the cytotoxicity of antibiotics and steroid to cultured porcine corneal endothelial cells; Wang HZ et al.; Intracameral injection (ICI) of antibiotics and steroid is an effective method to deliver drugs into eyeballs, and rapidly achieve therapeutic concentrations . The high intraocular concentrations, however, that occur by such injections can harm the corneal endothelium . The MTT assay, MTT {3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide}, has been used to test cytotoxicity of five antibiotics (including amphotericin-B, colistin-M, sulbenicillin, amikacin, cephradine) and a steroid, betamethasone, to cultured porcine corneal endothelial cells . The third passage of porcine corneal endothelial cells were plated into 96-well microtitration plates for drugs exposure . Cytotoxicities of the six drugs in different concentrations were compared, using exposure time as an independent variable . In its original and 10-fold ICI dose, only amphotericin-B among the six tested drugs showed significant cytotoxicity; the other drugs were considered safe . In a 100-fold ICI dose, amphotericin-B, colistin-M, and sulbenicillin were all toxic . Although a cell culture system utilizing the MTT assay is an in vitro method of testing for drug toxicity to the corneal endothelium, it nevertheless offers the advantages over in vivo methods . It is rapid, convenient, and economical . Large numbers of toxic compounds can be compared simultaneously, so that relative toxicities among different drugs and concentrations can be obtained, and be a guide for determining ICI dose, or as a reference for further in vivo testing.

Magn Reson Imaging, 1996, 14(6), 615 - 8
Dark ring sign: finding in patients with fungal liver lesions and transfusional hemosiderosis undergoing treatment with antifungal antibiotics; Kelekis NL et al.; OBJECTIVE: To describe the MR appearance of necrotizing fungal granulomas occurring in the liver of leukemic patients with hepatosplenic fungal disease and transfusional hemosiderosis on antifungal antibiotics . SUBJECTS AND METHODS: Four patients with acute myelogenous leukemia (n = 2) or acute lymphocytic leukemia (n = 2) who developed hepatosplenic fungal disease, and were treated with antifungal medication, underwent MRI examination on a 1.5 T MR imager . MR images were prospectively evaluated and correlated with liver biopsy (three patients), and clinical picture (one patient) . RESULTS: Multiple liver lesions measuring approximately 1 cm in diameter were identified in all patients . Lesions possessed a distinctive MR appearance: central mild hyperintensity with a peripheral ring of very low signal intensity on precontrast T1- and T2-weighted images . The central region of the lesions enhanced following gadolinium administration with the peripheral ring remaining low in signal intensity . CONCLUSION: Necrotizing fungal granulomas in the liver of patients with transfusional hemosiderosis on treatment with antifungal antibiotics have a distinctive appearance of moderate high signal intensity center on T1- and T2-weighted and postgadolinium MR images with a peripheral rim of low signal intensity . This appearance reflects the presence of iron-laden macrophages in the periphery of granulomas and may be expected in processes that initiate an immune response involving aggregation of macrophages in the liver of patients with transfusional iron overload.

Acta Microbiol Immunol Hung, 1996, 43(2-3), 107 - 14
Antibiotics and the host-parasite relationship (a short review); Gemmell CG; The last twenty years have witnessed an increasing interest in the concomitant action that an antibiotic may have on cells other than its primary target, the bacterial or fungal cell . It is now recognized that some may exert direct immunomodulatory effects (positive and negative) on cells of the host's immune response (polymorphonuclear neutrophils, macrophages and T lymphocytes) . Others may concentrate within phagocytic cells, remain bioactive therein and be transported involuntarily to sites of infection . In addition, there is evidence that a number of antibiotics, primarily those which act by inhibition of bacterial protein synthesis, interfere with the expression of structural virulence factors rendering the producer bacteria more or less susceptible to phagocytic ingestion and killing . It remains likely that some of all of these activities may occur in vivo during therapy.

Int Orthop, 1996, 20(4), 204 - 6
Antibiotic-associated colitis in orthopaedic patients; Boehler M et al.; Antibiotic-associated colitis was diagnosed in 23 orthopaedic patients: 17 had abdominal symptoms, 3 had a fever and the remaining 3 had no symptoms but increasing C-reactive protein values or white blood count . The antibiotic was clindamycin in 19, cephalosporins in 3 and a combination of vancomycin and fusidic acid intravenously in one . The antibiotics were stopped in 12, changed in 5 and continued in the remaining 5 . Oral treatment for colitis was given in 21 patients, and in one patient the only treatment was stopping the antibiotics . One patient died after a myocardial infarct; the remaining 22 were discharged after successful treatment of their primary condition and the colitis.

Drugs, 1996, 52 Suppl 2, 80 - 2
Antibiotic usage: pharmacoeconomic impact in a changing healthcare system; Milkovich G; There is limited experience in the healthcare field in terms of the evaluation of treatment costs . All too often, healthcare providers focus on the financial end-points (such as drug acquisition costs) as opposed to clinical end-points . This approach fails to view products from a broader perspective and tends to ignore the impact of a drug in terms of better patient compliance, fewer office visits, reduced length of hospital stay, or avoidance of hospitalisation . This article will briefly discuss the techniques used in the US to improve the utilisation of antibiotics, and describe the move towards the use of outpatient (i.e . outpatient care attached to a hospital, or in an infusion or clinic setting) or home therapy.

Scand J Gastroenterol Suppl, 1996, 218, 3 - 9
Dual and triple therapy regimens of antisecretory agents and antibiotics for the eradication of Helicobacter pylori: an overview; Ciociola AA et al.; BACKGROUND: Studies evaluating therapeutic regimens that combine antisecretory agents with antibiotics for the eradication of H . pylori have reported significant variations in efficacy . METHODS: We reviewed the published literature to compare H . pylori eradication rates in patients treated with either omeprazole, ranitidine bismuth citrate (RBC), or ranitidine plus metronidazole combined with either amoxicillin or clarithromycin . RESULTS: Wide variations in H . pylori eradication rates have been reported with omeprazole plus either amoxicillin (0-100%) or clarithromycin (42-88%) . Eradication rates ranging from 45% to 89% and from 74% to 94% have been reported with RBC plus either amoxicillin or clarithromycin, respectively . Eradication rates ranging from 48% to 90% have been reported with ranitidine plus metronidazole and amoxicillin and one study reported an eradication rate of 95% with ranitidine plus metronidazole and clarithromycin CONCLUSIONS: Well-controlled trials with ranitidine bismuth citrate plus clarithromycin suggest that this combination may provide the most consistent and effective regimen for the eradication of H . pylori infection.

Clin Ther, 1996 Jan-Feb, 18(1), 160 - 82
A cost-utility analysis of second-line antibiotics in the treatment of acute otitis media in children; Oh PI et al.; Newer antibiotics have higher acquisition costs than the first-line antibiotics but may offer superior outcomes, including enhanced eradication of resistant organisms, safety, and compliance in the treatment of acute otitis media . A rational choice among differing therapies should systematically address all these factors . We conducted a cost-utility analysis to compare the commonly used second-line antibiotics--cefaclor (CEF), amoxicillin-clavulanate (AMX-CLA), and erythromycin-sulfisoxazole (ERY-SULF) . A meta-analysis of comparative clinical trials was performed to derive point estimates with a 95% confidence interval for rates of success and adverse events . Costs for drugs, laboratory tests, and physician visits were obtained from the government formulary and fee schedules . The cost for management of adverse events was estimated from the findings of a survey of pediatricians . Utilities (preferences or ratings of health states) were derived from responses of physicians to a standardized scenario of acute otitis media with combinations of adverse events . These utilities were used to obtain quality-adjusted life-day (QALD) scores over a 30-day horizon as a measure of effectiveness . Overall cost and QALD were calculated using decision analytic modeling . CEF performed significantly better than the two other drug treatments with the lowest expected cost ($108.00) and highest outcome (28.15 QALD); AMX-CLA was second in cost and third in outcome ($119.00, 27.98 QALD); and ERY-SULF was third in cost and second in outcome ($120.00, 28.03 QALD) . These rankings were robust to variations in event rates over the 95% confidence interval . In this analysis, CEF was the most cost-effective antibiotic strategy for second-line therapy when differential success rates, adverse-event profiles, and impact on quality-of-life were considered.

Jpn J Antibiot, 1996 Jan, 49(1), 1 - 16
{Neurotoxicity of carbapenem compounds and other beta-lactam antibiotics}; Sunagawa M et al.; The neurotoxic potencies are considerably different among various beta-lactam antibiotics . Some carbapenem antibiotics, a new class beta-lactam antibiotic, also induce convulsion in human and laboratory animals . This article reviews the structure activity relationship for the neurotoxicity of beta-lactam antibiotics, especially carbapenems . As for the neurotoxicity of carbapenem antibiotics, the presence of amino group in the C-2 side chain is an important factor in inducing convulsion and the strength of basicity of the amino group is correlated with the convulsant activity . The beta-lactam ring of carbapenem is not necessary to evoke convulsions . The neurotoxicity of carbapenem antibiotics is related to only a part of the structure, including the C-2 side chain, but not to the carbapenem skeleton itself . In comparison with other beta-lactam antibiotics, it has been found that the structure responsible for the convulsive action of carbapenems is significantly different from penicillins and cephalosporins in which the beta-lactam ring is essential to evoke convulsion . The induction of convulsions by carbapenem antibiotics is predominantly caused through the inhibition of gamma aminobutyric acid receptor in a similar manner as with penicillins and cephalosporins . However, the detail mechanism may be different not only among carbapenems, cephalosporins, and penicillins but among carbapenem compounds themselves . It is important to know the neurotoxic potential of a compound by investigating the effect of direct administration into the central nervous system such as intraventricular administration, since the penetration through blood-brain barrier or the pharmacokinetic property is varied in seriously ill patients . Possible drug interactions regarding neurotoxicity are also discussed . We hope these findings described here will be helpful in developing more efficient and safer beta-lactam antibiotics of a new generation.

J Investig Allergol Clin Immunol, 1996 Jan-Feb, 6(1), 30 - 5
Booster responses in the study of allergic reactions to beta-lactam antibiotics; Lopez-Serrano MC et al.; The observation of negative skin and challenge tests to beta-lactams in some patients with prior histories of reactions to these antibiotics led us to develop a protocol ("booster study") which systematically included the performance of skin and challenge tests to beta-lactams ten to thirty days after the study to confirm the negative results . From a total of 430 patients who came to our outpatient clinic because of a reaction to a beta-lactam or unknown antibiotic, 249 completed the study . Out of the patients who completed the second phase, or "booster study," the results were positive in the first phase, or conventional study in 42 patients, and negative in 207 . The booster study was negative in 197 patients (95 percent) and positive in ten patients (5 percent) . Skin tests were positive in 5 of them (penicilloyl-polylysine: 5; benzylpenicillin: 3; amoxicillin: 2; minor determinant mixture: 1), and 5 patients developed an allergic reaction after rechallenge (benzylpenicillin: 4; amoxicillin: 1) . One patient with both negative skin tests and amoxicillin oral challenge in the booster study developed an immediate generalized urticaria with the oral intake of amoxicillin one month later at home; skin tests became positive at that moment . The negative results in the first phase of the study and the development of positive results in the second phase could be due to the existence of an immunological amnestic reaction or to sensitization after reexposure to beta-lactams in the diagnostic procedures.

Drug Chem Toxicol, 1996, 19(1-2), 121 - 30
Ultraviolet radiation-induced production of superoxide radicals by selected antibiotics; Ray RS et al.; The ability of certain drugs and chemicals to induce cutaneous phototoxicity and DNA damage has been attributed to free radical formation during photolysis . In this context we have observed that the synergistic action of commonly used antibiotics and ultraviolet radiation (UVR) exhibited strong superoxide radical (O2-) generation potential in the following order: benzylpenicillin > amphotericin > ampicillin > nystatin > spectinomycin > gentamicin . Commercially available penicillin, nystatin, ampicillin and gentamicin also generated O2- under similar conditions . The results suggest that due precaution are necessary to avoid UVR after the intake of photoreactive drugs.

Vopr Onkol, 1996, 42(3), 64 - 6
{Effectiveness of free and liposomal forms of platinum and anthracycline antibiotics for hepatic metastasis of GA-1 and P-388 tumors in mice}; Kaledin VI et al.; Liposome-entrapped platinum and anthracycline antibiotics showed similar advantages over their free forms in both experimental runs in being less toxic and more effective as a means of metastasis control . Since individual tumors differ in their sensitivity to different drugs, it might be suggested that liposomal forms of platinum coordination complexes may contribute to the hepatic metastasis drugs stockpile.

Br J Pharmacol, 1996 Jan, 117(2), 372 - 6
Increase in insulin release from rat pancreatic islets by quinolone antibiotics; Maeda N et al.; 1 . The present study was undertaken to elucidate the mechanism(s) of hypoglycaemia caused by quinolone antibiotics . We investigated the effects of various quinolone antibiotics on insulin release in rat pancreatic islets . 2 . At a non-stimulatory concentration of 3 mM glucose, lomefloxacin (LFLX) or sparfloxacin at 1 mM and pipemidic acid (0.1-1 mM) induced slight insulin release but tosufloxacin or enoxacin up to 100 microM did not . 3 . At the stimulatory concentration of 10 mM glucose, all quinolones augmented insulin release in a dose-dependent manner . LFLX (100 microM) shifted the dose-response curve of glucose-induced insulin release to the left without altering the maximal response . 4 . At 10 mM glucose, LFLX (100 microM) increased insulin release augmented by forskolin (5 microM) or 12-O-tetradecanoyl phorbol-13-acetate (100 nM) but not by raising the K+ concentration from 6 to 25 mM . 5 . Verapamil (50 microM) or diazoxide (50-400 microM) antagonized the insulinotropic effect of LFLX . 6 . These data suggest that quinolone antibiotics may cause hypoglycaemia by increasing insulin release via blockade of ATP-sensitive K+ channels.

Antimicrob Agents Chemother, 1996 Jan, 40(1), 50 - 4
Cytochrome P-450 complex formation in rat liver by the antibiotic tiamulin; Witkamp RF et al.; Tiamulin is a semisynthetic diterpene antibiotic frequently used in farm animals . The drug has been shown to produce clinically important--often lethal--interactions with other compounds . It has been suggested that this is caused by a selective inhibition of oxidative drug metabolism via the formation of a cytochrome P-450 metabolic intermediate complex . In the present study, rats were treated orally for 6 days with tiamulin at two different doses: 40 and 226 mg/kg of body weight . For comparison, another group received 300 mg of triacetyloleandomycin (TAO) per kg, which is equivalent to the 226-mg/kg tiamulin group . Subsequently, microsomal P-450 contents, P-450 enzyme activities, metabolic intermediate complex spectra, and P-450 apoprotein concentrations were assessed . In addition, effects on individual microsomal P-450 activities were studied in control microsomes at different tiamulin and substrate concentrations . In the rats treated with tiamulin, a dose-dependent complex formation as evidenced by its absorption spectrum and an increase in cytochrome P-4503A1/2 contents as assessed by Western blotting (immunoblotting) were found . The effects were comparable to those of TAO . Tiamulin induced microsomal P-450 content, testosterone 6 beta-hydroxylation rate, erythromycin N-demethylation rate, and the ethoxyresorufin O-deethylation activity . Other activities were not affected or decreased . When tiamulin was added to microsomes of control rats, the testosterone 6 beta-hydroxylation rate and the erythromycin N-demethylation were strongly inhibited . It is concluded that tiamulin is a potent and selective inducer-inhibitor of cytochrome P-450 . Though not belonging to the macrolides, the compound produces an effect on P-450 similar to those of TAO and related compounds.

Ann Pharmacother, 1996 Jan, 30(1), 31 - 4
Survey of antibiotic control policies in university-affiliated teaching institutions; Lesar TS et al.; OBJECTIVE: To determine the type and extent of antibiotic control policies currently in use in a group of university-affiliated teaching institutions . DESIGN: A survey of antibiotic control policies and procedures (e.g., antibiotic order sheets, formulary restrictions, automatic stop orders for specific indications) was developed . SETTING: The University Hospital Consortium (UHC), a nonprofit group of academic health centers located in 33 states throughout the US . PARTICIPANTS: The survey was mailed to 60 UHC members . RESULTS: The survey was returned by 48 (80%) institutions . Most hospitals use either restrictions (81%) and/or official recommendations (56%) to manage antibiotic use . Antibiotics were restricted most commonly by service or unit (69%), indication (69%), or to the infectious disease service (60%) . Antibiotic order sheets are used in 21 (44%) of the hospitals, of which 14 require completion by the prescriber . Monitoring of compliance with established restrictions is primarily the responsibility of the pharmacist processing the order (84%) and/or a clinical pharmacist (53%) . When an order does not comply with restrictions or compliance cannot be determined, the prescriber is contacted prior to dispensing in 77% and 83% of the cases, respectively . In cases of noncompliance in which the prescriber refuses to alter an order to meet restrictions, 40% of hospitals refuse to dispense the drug and 35% dispense the drug but refer the case to another authority (infectious disease service or pharmacy and therapeutics committee) . CONCLUSIONS: Considering the widespread use of antibiotic control programs, further investigation of the success of such programs in optimizing drug therapy, improving patient outcome, and cutailing the antibiotic budget within and among specific institutions is warranted.

Biotechniques, 1996 Jan, 20(1), 102 - 4, 106, 108-10
Bicistronic vector for the creation of stable mammalian cell lines that predisposes all antibiotic-resistant cells to express recombinant protein; Rees S et al.; We have developed an improved vector for the stable expression of recombinant protein in mammalian cells . In this vector, designated pCIN, both the recombinant cDNA and the neomycin phosphotransferase selection marker are transcribed from a single promoter element . To facilitate translation of the second open reading frame, the encephalomyocarditis virus internal ribosome entry site has been inserted into the expression cassette immediately before the start codon of this sequence . We report the use of this vector to generate stable cell lines expressing the human 5-HT1Da serotonin receptor and show that following transfection and clonal selection, all ten cell lines characterized express similar and high levels of receptor (1.5-11.9 pmol receptor/mg protein) . Use of pCIN should permit the rapid and efficient production of stable mammalian cell lines for the characterization of recombinant protein, as this vector appears to predispose all transfected cells to express such protein.

Rev Chir Orthop Reparatrice Appar Mot, 1996, 82(1), 59 - 62
{In vitro evaluation of antibiotic diffusion from antibiotic impregnated xenografts}; Gunal I et al.; PURPOSE OF THE STUDY: The purpose of the study was to evaluate xenografts as a slow release antibiotic delivery system, as xenografts also have excellent biocompatibility and osteogenesis-stimulating effect . MATERIAL: Xenograft (Unilab Surgibone) blocks of 5 x 5 x 5 mm were used in the study . Antibiotics used for impregnation were gentamicin sulphate, ciprofloxacin and penicillin G . METHODS: In the pilot study, xenograft blocks impregnated with gentamicin sulphate solution and the contact time was between 1/2 to 10 hours . Then the grafts were incubated and the antibiotic concentration was measured in the elution fluid changed every day . The minimum contact time to release the antibiotic 10 days over 0.5 microgram/ml was 8 hours . The 8 hours contact time was used in the main study to evaluate gentamicin sulphate, ciprofloxacin and penicillin G . The method was the same as in the pilot study . RESULTS: All antibiotics showed similar release patterns reaching their peaks on the 5th day and then gradually decreasing below the effective level (0.5 microgram/ml) approximately on day 10 . DISCUSSION: Although various materials have been used to deliver antibiotics, they have some certain disadvantages especially reduced biocompatibility . The superiority of xenografts over other materials, is not only biocompatibility but also to facilitate osteogenesis . The only objection may be the relatively short duration of release (10 days) but the length of antibiotherapy is controversial and standard 6 weeks of administration has no documented superiority over other time intervals . CONCLUSION: Our delivery system is superior to others as its function is not only to deliver antibiotics but has its place in orthopedic practice to fill defects and stimulate osteogenesis . Also the preparation of this system is not time and skill consuming.

Surg Today, 1996, 26(5), 314 - 22
Preoperative administration of antibiotics in patients with suspected acute appendicitis; Murao Y et al.; The effectiveness of administering antibiotics preoperatively to patients with suspected appendicitis was evaluated over a 2-year period in 105 consecutive patients who presented with right lower quadrant (RLQ) tenderness and a white blood cell (WBC) count of over 10,000/mm3 or a temperature of over 37 degrees C . All the patients were preoperatively administered cefazolin (CEZ), cefotiam (CTM), or fosfomycin (FOM) except those with apparent peritonitis, which resulted in the recovery of 41 patients (39%) . Of the remaining 64 patients, 14 (13%) had catarrhal appendicitis, 34 (32%), phlegmonous appendicitis, and 16 (15%), gangrenous appendicitis . Preoperatively, there were no significant differences among these groups in the WBC count or temperature . Following the administration of antibiotics, both these parameters decreased significantly in the patients with catarrhal appendicitis, although a slight RLQ tenderness persisted; in those with phlegmonous appendicitis, the WBC count decreased significantly, but the temperature remained elevated, with slight rebound tenderness in the RLQ; and in those with gangrenous appendicitis, there were no significant differences between the pre- and postoperative data in WBC count or temperature, and the abdominal symptoms did not change . These results show the value of administering antibiotics within 24h of the onset of symptoms indicative of acute appendicitis to allow time to evaluate the patients' condition, decide the operative indications, and prevent unnecessary laparotomy.

Scand J Gastroenterol Suppl, 1996, 215, 105 - 10
Effects of permanent eradication or transient clearance of Helicobacter pylori on histology of gastric mucosa using omeprazole with or without antibiotics; Solcia E et al.; Changes in Helicobacter pylori-associated gastritis of the antrum and corpus were investigated in a large number of patients treated with omeprazole, with or without the addition of amoxycillin . To investigate the role of H . pylori-associated gastritis in ulcerogenesis and its interplay with omeprazole, biopsies were taken and evaluated according to the Sydney system . Successful eradication of H . pylori (assessed histologically 4 weeks after the end of therapy) led to prompt and persistent suppression of gastritis activity, slow, partial regression of mononuclear inflammation and an ulcer recurrence rate of only 14% during the 6 months' follow-up . In patients treated with omeprazole and placebo, or where eradication treatment with omeprazole and amoxycillin had failed, transient clearance of H . pylori from the antral (but not oxyntic) mucosa was seen . In both of these groups of patients transient regression in the antrum, and worsening in the corpus, of gastritis activity and mononuclear inflammation were evident, coupled with ulcer recurrence rates of 72 and 46%, respectively . It was concluded that H . pylori colonization and gastritis activity play a crucial role in ulcerogenesis, that acid inhibition treatment improves antral H . pylori gastritis and worsens the oxyntic mucosal gastritis, and that this can be prevented by eradication of the H . pylori infection.

Vet Res, 1996, 27(2), 97 - 106
Healing of muscle trauma after intramuscular injection of antibiotics in sheep: correlations between clinical, macroscopic and microscopic scores; Mikaelian I et al.; The present study aimed to predict the resultant healing from early lesions (found days 3 and 10 post injection) caused by the intramuscular injection of veterinary antibiotic formulations . Nineteen marketed drugs were selected in order to screen a wide range of irritation conditions at the injection site . Nineteen ewes were each injected intramuscularly with one of the formulations . Each injection was at a different site, 3 and 10 days prior to slaughter . Fourteen of these ewes also received intramuscular injections at two other sites 21 and 32 days prior to slaughter . The tolerance was monitored by clinical examination of the injection site and by gross and microscopic pathology . Myodegeneration and fibre necrosis were determined histologically . The clinical scores did not correlate with the other findings . Myodegeneration correlated with the size of the lesion on day 3 post-injection and was not found thereafter . Although occasionally found alone, it was generally associated with and surrounded by fibre necrosis . When myodegeneration was the only lesion, regeneration was complete by day 21 and the fibrosis was minimal or absent . Necrosis at day 10 post-injection correlated with necrosis at days 3, 21 and 32 post-injection . Fibrosis became prominent around the necrotic muscles from day 10 post-injection . Healing from necrosis was slow with, in some instances, encapsulated debris still persisting at day 32 post-injection . The tissue irritation index correlated well with myodegeneration and necrose (acute lesions) and fibrose and necrose (older lesions) . Thus, after considering a large sample of antibiotic formulations, this study indicated that healing could be predicted from the muscle fibre histopathology at days 3 and 10 post-injection . If myodegeneration was found alone, full recovery within 21 days could be predicted . If fibre necrosis was extensive, the healing involved encapsulating the necrotic tissues and thus resulted in extensive scar formation . The tissue changes explained why the irritation index of the lesions at days 21 and 32 post-injection could be predicted from their irritation index at days 3 and 10 post-injection . Likewise, the size of the lesion at days 21 and 32 post-injection could not be predicted from its size at day 3 post injection.

J Mal Vasc, 1996, 21 Suppl A, 146 - 51
{Antibiotic bonding on arterial prostheses: a necessity}; Goeau-Brissonniere O; The introduction of arterial grafts made of polyester impregnated with a protein network is an important advance . Besides preventing leakage, impregnation makes it possible to bind active molecules, particularly antibiotics . Rifampicin is one of the antibiotics with an activity spectrum adapted to micro-organisms involved in graft infections and with a particular affinity for the protein network impregnating certain grafts . Rifampicin's affinity for gelatine means that large amounts of the antibiotic can be bound simply by dipping the graft in an antibiotic solution . This technique has been shown to be useful for both prevention and treatment in an experimental model . These preliminary findings have led to a multicentric randomized European trial which has provided encouraging results showing a decrease in the overall and early infection rates.

Pol J Pathol, 1996, 47(1), 13 - 7
Antibiotic associated nephropathy; Pospishil YO et al.; Renal biopsies of 43 patients who developed renal complications after treatment with antibiotics were studied . The treatment with antibiotics in these cases was used for many different reasons such as: bronchitis, bronchopneumonia, cystitis, tonsillitis, sepsis, peritonitis, gangrene of the foot and tuberculosis . The renal function of these patients, before the treatment with antibiotics was normal . The biopsies were studied by light, electron and immunofluorescence microscopy . In 43 cases treated with antibiotics renal changes were shown . Three types of morphologic changes were found: acute tubular necrosis (ATN) (13 cases), acute tubulo-interstitial diseases (ATID) (21 cases), focal glomerulonephritis with crescents (FGN) (9 cases) . The renal pathologic changes were most commonly seen in patients treated with 2 groups of antibiotics: aminoglycosides (21 cases) and antibiotics of the penicillin group (15 cases) . The most characteristic feature of aminoglycosides is their direct toxic effect leading to ATN . Antibiotics of the penicillin type more commonly caused an allergic reaction leading to ATID (secondary to cellular mechanisms) or FGN (secondary to a predominantly humoral mechanism) . Renal changes in the use of other antibiotics were much less manifest and were usually due to a hypersensitivity reaction . Cephalosporins, if used in combination with other antibiotics can increase their nephrotoxicity.

Yakugaku Zasshi, 1996 Jan, 116(1), 1 - 20
{Synthesis of lactone ring-containing bioactive natural products . Cardiotonic steroids, naphthoquinone antibiotics, and tetronic acid ionophore antibiotics}; Yoshii E; Achievements in the synthestic study on cardiotonic steroids, pyranonaphthoquinone antibiotics, and tetronic acid ionophore antibiotics from author's laboratory are reviewed.

Pediatr Infect Dis J, 1996 Jan, 15(1), 18 - 22
Randomized, double blind comparison of brand and generic antibiotic suspensions: II . A study of taste and compliance in children; El-Chaar GM et al.; BACKGROUND: The taste of oral liquid medications influences compliance in children . Generic preparations are prescribed to reduce cost and may taste worse than brand name products . METHODS: This was a prospective, randomized, double blind, crossover trial of the differences in taste and compliance between brand and generic antibiotic suspensions in children 3 to 14 years of age . Verbal and visual assessment methods were used to assess taste, and compliance was measured by the amount of drug returned after use . RESULTS: Ten children in each of the cephalexin and erythromycin-sulfisoxazole groups did not report that the brand and generic formulations tasted differently . Fifteen children thought that brand trimethoprim-sulfamethoxazole tasted better than the generic preparation . CONCLUSIONS: Brand name oral liquid antibiotics do not necessarily taste better than their generic counterparts . Despite preference for the taste of brand trimethoprim-sulfamethoxazole, all of the children in this study were compliant with both brand and generic medications.

Pediatr Infect Dis J, 1996 Jan, 15(1), 14 - 17
Randomized, double blind comparison of brand and generic antibiotic suspensions: I . A study of taste in adults; Samulak KM et al.; BACKGROUND: A belief that brand oral liquid medications taste better than their generic counterparts may influence prescribing habits among pediatricians . METHODS: We undertook a prospective, randomized, double blinded, comparative evaluation of the taste of brand and generic erythromycin ethylsuccinate, cephalexin monohydrate, erythromycin ethylsuccinate/sulfisoxazole, penicillin V potassium and trimethoprim-sulfamethoxazole in 42 adult volunteers . Subjects tasted one class of brand and generic antibiotics and rated them according to smell, texture, taste and aftertaste . RESULTS: At least one generic preparation of cephalexin, erythromycin ethylsuccinate/sulfisoxazole and penicillin V potassium was rated equal in taste to the respective brand name products . However, brand erythromycin estolate and trimethoprim-sulfamethoxazole name brand suspensions rated significantly higher than the other products tested . CONCLUSIONS: Based on our results brand name oral antibiotic formulations do not necessarily taste better than their generic counterparts.

Microbiology, 1996 Jan, 142 ( Pt 1), 123 - 32
Accumulation of the angucycline antibiotic rabelomycin after disruption of an oxygenase gene in the jadomycin B biosynthetic gene cluster of Streptomyces venezuelae; Yang K et al.; DNA from a region downstream of and overlapping the polyketide synthase (PKS) gene cluster for jadomycin B biosynthesis in Streptomyces venezuelae was cloned and sequenced . Analysis of the nucleotide sequence located one complete ORF (ORF6), an incomplete one representing the 3' region of ORF4 in the PKS cluster, and a second incomplete one (ORF7) . The deduced amino acid sequences for ORFs 6 and 7 resemble those of oxygenases . Since a plausible biosynthetic pathway for jadomycin B includes an angular polyketide intermediate that undergoes oxidative ring fission before condensation with an amino acid, we subcloned one of the presumptive oxygenase genes (ORF6) in a segregationally unstable shuttle vector (pHJL400) and disrupted it by inserting the gene for apramycin resistance . Transformation of S . venezuelae with the disruption vector and selection for apramycin resistance gave mutants blocked in jadomycin biosynthesis . Southern hybridization confirmed that gene replacement had occurred . Cultures of the mutants accumulated a metabolite identified by comparison with an authentic sample as rabelomycin, a non-nitrogenous polyketide-derived antibiotic originally isolated from Streptomyces olivaceus.

Am J Med, 1996 Jan, 100(1), 17 - 23
Randomized comparison between antibiotics alone and antibiotics plus granulocyte-macrophage colony-stimulating factor (Escherichia coli-derived in cancer patients with fever and neutropenia; Anaissie EJ et al.; PURPOSE: A prospective, randomized study was conducted to determine if recombinant human granulocyte-macrophage colony-stimulating factor (rh-GMCSF) (Escherichia coli-derived) could improve response rates to antibiotic therapy and shorten the duration of neutropenia in cancer patients . PATIENTS and METHODS: A total of 107 febrile neutropenic cancer patients were randomly assigned to empiric therapy with ticarcillin-clavulanate (4 g ticarcillin + 0.1 g clavulanate i.v . every 4 hours) plus netilmicin (2 mg/kg i.v . every 8 hours) with or without rh-GMCSF (3 micrograms/kg per day i.v.) . Clinical improvement, duration of neutropenia, and toxicity were monitored . RESULTS: Addition of rh-GMCSF to the antibiotics significantly improved the response rate (96% versus 82%, P = 0.03), but not the survival rate (93% versus 93%), in the evaluable patients . This difference in response rate was not significant when considering all patients in an intent-to-treat analysis . The number of patients who recovered from severe neutropenia ( < 100 cells/microliter) during the period of observation in the study was significantly greater among patients receiving the colony-stimulating factor, although the median duration of neutropenia was not affected . Superinfections and subsequent infections were not significantly different among the two treatment regimens . Side effects were more common among patients treated with the colony-stimulating factor . CONCLUSIONS: Our data do not support the routine administration of rh-GMCSF with antibiotics for patients with fever and neutropenia . Further studies should be conducted to identify those patients most likely to benefit from rh-GMCSF therapy, such as patients with persistent profound neutropenia and refractory infections.

Biopolymers, 1996, 40(1), 141 - 55
Molecular structure and mechanisms of action of cyclic and linear ion transport antibiotics; Duax WL et al.; Ionophores are antibiotics that induce ion transport across natural and artificial membranes . The specific function of a given ionophore depends upon its selectivity and the kinetics of ion capture, transport, and release . Systematic studies of complexed and uncomplexed forms of linear and cyclic ionophores provide insight into molecular mechanisms of ion capture and release and the basis for ion selectivity . The cyclic dodecadepsipeptide valinomycin, cyclo{(-L-Val-D-Hyi-D-Val-L-Lac)3-}, transports potassium ions across cellular membrane bilayers selectively . The x-ray crystallographic and nmr spectroscopic data concerning the structures of Na+, K+, and Ba+2 complexes are consistent and provide a rationale for the K+ selectivity of valinomycin . Three significantly different conformations of valinomycin are observed in anhydrous crystals, in hydrated crystals grown from dimethylsulfoxide, and in crystals grown from dioxane . Each of these conformations suggests a different mechanism of ion capture . One of the observed conformations has an elliptical structure stabilized by four 4<--1 intramolecular hydrogen bonds and two 5<--1 hydrogen bonds . Ion capture could be readily achieved by disruption of the 5<--1 hydrogen bonds to permit coordination to a potassium ion entering the cavity . The conformation found in crystals obtained from dimethyl sulfoxide is an open flower shape having three petals and three 4<--1 hydrogen bonds . Complexation could proceed by a closing up of the three petals of the flower around the desolvating ion . In the third form, water molecules reside in the central cavity of a bracelet structure having six 4<--1 hydrogen bonds . Two of these bracelets stack over one another with their valine-rich faces surrounding a dioxane molecule . The stacked molecules form a channel approximately 20 A in length, suggesting that under certain circumstances valinomycin might function as a channel . A series of analogues of valinomycin differing in ring composition and size have been synthesized and their transport properties tested . Peptide substitution and chiral variation in the dodecadepsipeptide can result in stabilization or modification of the different conformers . While contraction of the ring size results in loss of ion transport properties, expansion of the ring size permits complexation of larger ions and small positively charged molecules . Gramicidin A is a pentadecapeptide that functions as a transmembrane channel for transporting monovalent cations . Crystal structures of the cesium chloride complex and two uncomplexed forms of gramicidin A have been reported . In all three structures the gramicidin A molecule is a left-handed, antiparallel, double-stranded helical dimer . In the cesium complex the beta 7.2-helix has 6.4 residues per turn with an internal cavity large enough to accommodate cesium ions . In the uncomplexed structures the channel is 31 A long and has 5.6 amino acids per turn . Because the helix is too tightly wound to permit ion transport, ion transport would require breaking and reforming of hydrogen bonds.

Orthop Clin North Am, 1996 Jan, 27(1), 47 - 52
The use of antibiotics for wound prophylaxis in spinal surgery; Rimoldi RL et al.; The principle of spinal surgery prophylaxis is to prevent naturally occurring organisms from infecting a sterile site . Avoiding infection is the most important concern in decreasing morbidity in the immediate perioperative period . Prophylactic cephalosporin is mandatory . Suction drains should be used until output is minimal . This lessons the chance of hematoma formation . Hematomas are excellent culture media and may result in seromas . Aspiration of seromas that are painful can lead to another source of possible infection . The efficacy of topical irrigants in preventing infections during lumbar spine surgery remains to be answered.

J Biol Chem, 1995 Dec 22, 270(51), 30359 - 70
The role of tryptophans 371 and 395 in the binding of antibiotics and the transport of sugars by the D-galactose-H+ symport protein (GalP) from Escherichia coli; McDonald TP et al.; The interactions between the D-galactose-H+ symporter (GalP) from Escherichia coli and the inhibitory antibiotics, cytochalasin B and forskolin, and the substrates, D-galactose and H+, have been investigated for the wild-type protein and the mutants Trp-371-->Phe and Trp-395-->Phe, so that the roles of these residues in the structure-activity relationship could be assessed . Neither mutation prevented photolabeling by either {4-3H}cytochalasin B or by 3-{125I}iodo-4-azidophenethyl-amido-7-O-succinyldesacetylforskolin ({125I}APS-forskolin) . However, measurements of protein fluorescence show that both residues are in structural domains, the conformations of which are perturbed by the binding of cytochalasin B or forskolin . Moreover, both mutations cause a substantial decrease in the affinity of the inward-facing site of the GalP protein for cytochalasin B, 10- and 43-fold, respectively, but have little effect upon the affinity of this site for forskolin, 0.8- and 2.6-fold reductions, respectively . Both these mutations change the equilibrium between the putative outward- (T1) and inward-facing (T2) conformations, so that the inward-facing form is more favored . They also stabilize a different conformational state, "T3-antibiotic," in which the initial interactions between the protein and antibiotics are tightened . Overall, this has the effect of compensating for the reduction in affinity for cytochalasin B, so that the respective overall Kd values are 0.74- and 3.5-fold that of the wild type, while causing a slight increase, 1.5- and 3.2-fold, respectively, in affinity of the mutants for forskolin . The Trp-371-->Phe mutation causes a 15-fold reduction in the affinity of the inward-facing site for D-galactose, suggesting that this residue forms part of the sugar binding site . In contrast, the Trp-395-->Phe mutation has no effect upon the affinity of the inward-facing site for D-galactose . These effects may be related to the reduction in galactose-H+ symport activity only in the Trp-371-->Phe mutant, although it still effects active transport to the same extent as the Trp395-->Phe mutant . However, there is a 10-20-fold increase in the Km values for energized transport of D-galactose for both mutants.

Brain Res, 1995 Dec 15, 704(1), 135 - 40
Endocytosis of aminoglycoside antibiotics in sensory hair cells; Hashino E et al.; Immuno-gold electron microscopy was used to assess the uptake pathways of aminoglycoside antibiotic kanamycin (KM) in sensory hair cells . Accumulation of gold particles was evident on the plasma membrane as well as in large smooth vesicles beneath the apical surfaces of hair cells 12 h after a systemic administration of KM . Immuno-gold was exclusively localized in the vesicles 27 h post-injection . Cationic ferritin, a membrane-bound insoluble marker, was colocalized with KM in the vesicle structures after their simultaneous in vitro application . These results strongly suggest that KM is taken up into sensory hair cells via receptor-mediated endocytosis at their apical surfaces . In addition, the profound time lag between KM uptake and hair cell death suggests involvement of targeting mechanisms in cytotoxic signalling pathways of the drugs.

Biochim Biophys Acta, 1995 Dec 13, 1240(2), 167 - 78
Identification of the structural elements of amphotericin B and other polyene macrolide antibiotics of the hepteane group influencing the ionic selectivity of the permeability pathways formed in the red cell membrane; Cybulska B et al.; The selectivity of the transmembrane permeability induced by polyene antibiotics was studied in human erythrocytes and related to the hemolytic potency of the drugs . The selectivity induced was differently, dependent on the antibiotic structure in aromatic (vacidin A, gedamycin) and nonaromatic heptaenes (amphotericin B, candidin) . Aromatic heptaenes were more effective than nonaromatic in inducing permeability to K+ . For both groups of antibiotics, permeability to K+ was not affected by substitution at the carboxyl group but important differences in the induction of permeability to H+, OH- and Cl- were found . The strongly hemolytic aromatic heptaenes vacidin A and gedamycin exhibited much higher protonophoric activity than the nonaromatic ones: amphotericin B, and candidin . The protonophoric properties of aromatic heptaenes were related to the presence of a free carboxyl group in the antibiotic molecule . Indeed the esterification or amidation of the carboxyl group of vacidin A or gedamycin eliminated the ability of the antibiotic to increase H+ conductance and consequently diminished their hemolytic activity to an important extent . Both groups of antibiotics differed also in the efficiency of anion permeability induction . Only unsubstituted aromatic heptaenes, at high concentration, induced Cl-/OH- exchange and conductive flux of Cl- in a concentration-dependent manner . Substitution at the carboxyl group of vacidin A or gedamycin eliminated this property . Amphotericin B as well as its carboxyl-substituted derivatives formed a pathway characterized by low K+ over Cl- selectivity, whatever the concentration . The hemolytic activity, related to K+ permeability increased by heptaenes was dependent on simultaneous increase of the permeability to anions, and net KCl influx . Carboxyl-substituted derivatives of aromatic heptaenes presenting a remarkably high selectivity for K+, had consequently a very poor hemolytic activity.

Pharmacol Toxicol, 1995 Dec, 77(6), 365 - 70
Cytotoxic effects of four antibiotics on endothelial cells; Lanbeck P et al.; Intravenous administration of antibiotics often causes local pain and thrombophlebitis at the site of injection . An in vitro model that could predict these effects would be of great value . In this study the effects of four antibiotics, benzylpenicillin, cefuroxime, dicloxacillin and erythromycin, have been evaluated on three types of endothelial cells in culture . The cell types employed were primary culture from human umbilical vein, primary culture from bovine aorta, and the cell line EA-hy 926, a hybride endothelial cell . These cells were exposed to antibiotics for 24 hr and subsequently toxic effects on cells were evaluated by three different assays . Benzylpenicillin was atoxic in all types of cells and in all assays, in contrast to the other antibiotics . The other three antibiotics exerted dose dependent toxic effects in all investigated cells when DNA-synthesis and total cell protein were used as toxicity assays but the results varied between the cell types . There were no significant differences between the effects of cefuroxime, dicloxacillin and erythromycin on bovine endothelial cells . In the other cell types, however, there were significant differences between some drugs but the outcome depended on the cell type . It is concluded that it is possible to show differences between the effect of antibiotics on endothelial cells, but the result depends on the cell type employed.

Monaldi Arch Chest Dis, 1995 Dec, 50(6), 472 - 6
Empirical antibiotic therapy and lower respiratory tract infections: European guidelines and current practices; Woodhead M; Guidelines for the management of lower respiratory tract infection have been published in four European countries . The scope of each of these articles is reviewed and the similarities, differences and deficiencies highlighted . Very little is known about how lower respiratory tract infections (LRTIs) are managed in routine practice in Europe, especially in the community . The available data suggest major differences in antibiotic use between countries which is likely to be multifactorial in origin.

Pharm Res, 1995 Dec, 12(12), 1917 - 23
A semisynthetic Quillaja saponin as a drug delivery agent for aminoglycoside antibiotics; Recchia J et al.; PURPOSE: The purpose of this study was to investigate the utility of a purified, semisynthetic saponin, DS-1, prepared by deacylation of a naturally occurring saponin from the bark of the Quillaja saponaria Molina tree, as a permeation enhancer for mucosal delivery of the aminoglycosides, gentamicin and tobramycin . METHODS: Gentamicin or tobramycin formulations, with and without DS-1, were administered to rats nasally, ocularly, and rectally . Serum aminoglycoside levels following mucosal application were compared with those administered intramuscularly . Gentamicin formulations, with and without DS-1, were administered intranasally to mice 60 minutes after a lethal bacterial challenge . To ascertain nasal irritation potential, DS-1 nosedrops were administered to rats twice daily for 7 days in the right nostril only . Comparison of the left (internal control) and right nostril was made with a control group that received only buffer . RESULTS: Significant transport across mucous membranes was only observed in formulations containing DS-1 . This effect on drug delivery was transient . Administration of an intranasal gentamicin/DS-1 formulation reversed the lethal bacterial challenge in mice, demonstrating that biological activity was retained after absorption . Nasal irritation was not observed in groups receiving DS-1 nosedrops, which were identical to control groups . CONCLUSIONS: DS-1 has potential as a transmucosal delivery agent for the aminoglycoside antibiotics.

Br J Pharmacol, 1995 Dec, 116(7), 3021 - 7
Stereoselective uptake of beta-lactam antibiotics by the intestinal peptide transporter; Wenzel U et al.; 1 . The stereoselective transport of beta-lactam antibiotics has been investigated in the human intestinal epithelial cell line, Caco-2, by use of D- and L-enantiomers of cephalexin and loracarbef as substrates . 2 . The L-isomers of cephalexin, loracarbef and dipeptides displayed a higher affinity for the oligopeptide/H(+)-symporter in Caco-2 cells than the D-isomers . This was demonstrated by inhibition of the influx of the beta-lactam, {3H}-cefadroxil . 3 . By measurement of the substrate-induced intracellular acidification in Caco-2 cells loaded with the pH-sensitive fluorescent dye BCECF (2',7'-bis(2-carboxyethyl)-5-(6)-carboxy-fluorescein), it was demonstrated for the first time that L-isomers of beta-lactams not only bind to the peptide transporter with high affinity but are indeed transported . 4 . Efficient proton-coupled transport of L-beta-lactam antibiotics was also shown to occur in Xenopus laevis oocytes expressing the cloned peptide transporter PepT1 from rabbit small intestine . 5 . Both cell systems therefore express a stereoselective transport pathway for beta-lactam antibiotics with very similar characteristics and may prove useful for screening rapidly the oral availability of peptide-derived drugs.

Br J Pharmacol, 1995 Dec, 116(7), 3014 - 20
Dual mechanisms of GABAA response inhibition by beta-lactam antibiotics in the pyramidal neurones of the rat cerebral cortex; Fujimoto M et al.; 1 . The effects of beta-lactam antibiotics on the gamma-aminobutyric acid (GABA)-induced Cl- current were investigated in pyramidal neurones freshly dissociated from the rat frontal cortex by the use of a nystatin-perforated patch recording mode under voltage-clamp conditions . 2 . The GABA-induced inward current increased in a concentration-dependent manner with an EC50 of 6.7 x 10(-6) M at a holding potential of -40 mV . The GABA response was accompanied by an increase in the membrane conductance and reversed at near the Cl- equilibrium potential . 3 . All beta-lactams (penicillin, imipenem, aztreonam and cefotiam) inhibited the 10(-5) M GABA-induced response in a concentration-dependent manner with an IC50 and Hill coefficient of 1.3 x 10(-3) M and 0.64 for penicillin, 9.6 x 10(-4) M and 0.83 for imipenem, 2.5 x 10(-3) M and 9.99 for aztreonam, and 2.9 x 10(-4) M and 1.03 for cefotiam . 4 . Imipenem inhibited the GABA-response competitively while penicillin inhibited the same response in a noncompetitive fashion . 5 . The inhibitory action of imipenem showed no voltage-dependency, whereas the effect of penicillin was voltage-dependent . 6 . It is thus proposed that some classes of beta-lactams, including imipenem may have a mechanism that is different from penicillin and competitively affects the GABAA receptor.

Bioorg Khim, 1995 Dec, 21(12), 925 - 32
{14-O-hemiesters and 13-hydrazones of anthracyline antibiotics of the daunorubicin series . Synthesis and cytostatic activity with respect to tumor cells sensitive or resistant to doxorubicin}; Povarov LS et al.; Doxorubicin and 14-hydroxycarminomycin 14-O-hemiadipates and 14-O-hemipimelates, synthesized from 14-bromo derivatives of daunorubicin and carminomycin and monosodium adipate and pimelate, were converted to the corresponding N-trifluoroacetylated compounds . 13-(4-Methylpiperazine-1-yl)imino derivatives of the anthracycline antibiotics were also obtained . The cytostatic activity of the compounds synthesized was studied using a panel of human and animal tumor cell lines sensitive or resistant to doxorubicin . N-Trifluoroacetylation of the antibiotics resulted in a decrease in the cytostatic activity . The activity of the water-soluble 13-(4-methylpiperazine-l-yl)imino derivatives is close to that of the corresponding parent antibiotics.

Biophys J, 1995 Dec, 69(6), 2541 - 57
Self-association of the polyene antibiotic nystatin in dipalmitoylphosphatidylcholine vesicles: a time-resolved fluorescence study; Coutinho A et al.; The interaction between Nystatin and small unilamellar vesicles of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine, both in gel (T = 21 degrees C) and in liquid-crystalline (T = 45 degrees C) phases, was studied by steady-state and time-resolved fluorescence measurements by taking advantage of the intrinsic tetraene fluorophore present in this antibiotic . It was shown that Nystatin aggregates in aqueous solution with a critical concentration of 3 microM . The enhancement in the fluorescence intensity of the antibiotic was applied to study the membrane binding of Nystatin, and it was shown that the antibiotic had an almost fivefold higher partition coefficient for the vesicles in a gel (P = (1.4 +/- 0.1) x 10(3)) than in a liquid-crystalline phase (P = (2.9 +/- 0.1) x 10(2)) . Moreover, a time-resolved fluorescence study was used to examine Nystatin aggregation in the membrane . The emission decay kinetics of Nystatin was described by three and two exponentials in the lipid membrane at 21 degrees C and 45 degrees C, respectively . Nystatin mean fluorescence lifetime is concentration-dependent in gel phase lipids, increasing steeply from 11 to 33 ns at an antibiotic concentration of 5-6 microM, but the fluorescence decay parameters of Nystatin were unvarying with the antibiotic concentration in fluid lipids . These results provide evidence for the formation of strongly fluorescent antibiotic aggregates in gel-phase membrane, an interpretation that is at variance with a previous study . However, no antibiotic self-association was detected in a liquid-crystalline lipid bilayer within the antibiotic concentration range studied (0-14 microM).

Acta Crystallogr B, 1995 Dec 1, 51 ( Pt 6), 987 - 99
Structures of quinoxaline antibiotics; Sheldrick GM et al.; The crystal structures of three quinoxaline antibiotics-echinomycin 2QN, triostin C and the C222(1) form of triostin A--have been determined, and the structure of the P2(1)2(1)2(1) form of triostin A has been re-refined against our previously reported data . The molecular conformations are compared with those deduced from NMR data and those reported for two complexes of triostin A with oligonucleotides . Although the depsipeptide ring conformations are basically similar, the effective twofold molecular symmetry is violated by the folding of one of the quinoxaline chromophores in echinomycin 2QN and by a rotation of one of the ester planes with the formation of an intramolecular hydrogen bond in triostin C . In the oligonucleotide complexes of triostin A the chirality of the disulfide bridge is inverted . The alanine NH groups are involved in intermolecular hydrogen bonds in all four structures, and (except in echinomycin 2QN) the stacking of the chromophores in the crystal emulates the intercalation involved in DNA complex formation . In echinomycin 2QN, the antibiotic molecules are hydrogen bonded to form a helix along the crystallographic 6(5) screw axes, with a channel of disordered solvent running through the middle of the helix . Crystal data: (1), echinomycin 2QN, C53H66N10O12S2.2.5(C3H6O).2.5(H2O), M(r) = 1289.5, hexagonal, P6(5), a = b = 22.196(15), c = 24.64 (2) A, V = 10,513 (13) A3, Z = 6, Dx = 1.222 Mg m-3, lambda (Cu K alpha) = 1.5418 A, mu = 1.275 mm-1, T = 193 K, R = 9.0% for 4828 I > 2 sigma (I) and 11.8% for all 7102 unique reflections; (2), triostin C, C54H70N12O12S2.0.67(CHCl3).0.67(H2O), M(r) = 1234.2, orthorhombic, P2(1)2(1)2(1), a = 16.054 (8), b = 17.128 (9), c = 22.706 (12) A, V = 6244 (6) A3, Z = 4, Dx = 1.313 Mg m-3, lambda (Mo K alpha) = 0.71073 A, mu = 0.239 mm-1, T = 188 K, R = 7.7% for 4678 I > 2 sigma (I) and 14.0% for all 7260 unique reflections; (3), triostin A, C50H62N12O12S2.2(C7H14O2), M(r) = 1347.6, orthorhombic, P2(1)2(1)2(1), a = 20.94 (2), b = 18.53 (2), c = 18.80 (2) A, V = 7292 (13) A3, Z = 4, Dx = 1.228 Mg m-3, lambda (Cu K alpha) = 1.5418 A, mu = 1.245 mm-1, T = 293 K, R = 6.8% for 2116 I > 2 sigma (I) and 9.3% for all 2928 unique reflections; (4), triostin A, C50H62N12O12S2.HCl.2(C3H7NO), M(r) = 1269.9, monoclinic, C222(1), a = 10.622 (10), b = 17.035 (17), c = 35.21 (3) A, V = 6371 (10) A3, Z = 4, Dx = 1.324 Mg m-3, lambda (Mo K alpha) = 0.71073 A, mu = 0.199 mm-1, T = 153 K, R = 7.5% for 2164 I > 2 sigma (I) and 13.2% for all 3402 unique reflections . Extensive use was made of restraints on the geometrical and displacement parameters in the successful anisotropic refinement of these structures against weak data.

J Pharmacol Exp Ther, 1995 Dec, 275(3), 1631 - 7
Cloning and characterization of a rat H+/peptide cotransporter mediating absorption of beta-lactam antibiotics in the intestine and kidney; Saito H et al.; A complementary DNA (cDNA) encoding the rat H+/peptide cotransporter (PepT1) was isolated, and the transport characteristics of orally active beta-lactam antibiotics were assessed by measuring uptake into Xenopus oocytes expressing the rat PepT1 . The rat PepT1 cDNA encoded a 710-amino acid protein with 77% identity to the rabbit PepT1 . The message for rat PepT1 was approximately 2.9 kilobases and was found predominantly in the small intestine, whereas reverse transcription-polymerase chain reaction amplification revealed that the message was expressed both in the small intestine and in the kidney cortex . The 75-kDa protein was identified by translation of in vitro synthesized transcript of rat PepT1 cDNA by use of rabbit reticulocyte lysates and by Western blot analysis with a specific antibody against the rat PepT1 . When expressed in Xenopus oocytes, rat PepT1 stimulated the uptake of ceftibuten (anion) and cephradine (zwitterion) in the presence of an inward H+ gradient, and the expressed uptake was inhibited by excess dipeptides . Kinetic analysis revealed that ceftibuten has 14-fold higher affinity for the rat PepT1 than cephradine . These findings suggest that the rat PepT1 mediates H(+)-coupled uphill transport of the oral beta-lactam antibiotics across the brush-border membranes of intestinal and renal proximal tubular cells.

J Bacteriol, 1995 Dec, 177(24), 7100 - 4
Purification and regulatory properties of MarA protein, a transcriptional activator of Escherichia coli multiple antibiotic and superoxide resistance promoters; Jair KW et al.; Expression of the marA or soxS genes is induced by exposure of Escherichia coli to salicylate or superoxides, respectively . This, in turn, enhances the expression of a common set of promoters (the mar/soxRS regulons), resulting in both multiple antibiotic and superoxide resistance . Since MarA protein is highly homologous to SoxS, and since a MalE-SoxS fusion protein has recently been shown to activate soxRS regulon transcription, the ability of MarA to activate transcription of these genes was tested . MarA was overexpressed as a histidine-tagged fusion protein, purified, cleaved with thrombin (leaving one N-terminal histidine residue), and renatured . Like MalE-SoxS, MarA (i) activated the transcription of zwf, fpr, fumC, micF, nfo, and sodA; (ii) required a 21-bp "soxbox" sequence to activate zwf transcription; and (iii) was "ambidextrous," i.e., required the C-terminal domain of the alpha subunit of RNA polymerase for activation of zwf but not fumC or micF . Thus, the mar and soxRS systems use activators with very similar specificities and mechanisms of action to respond to different environmental signals.

J Am Vet Med Assoc, 1995 Dec 1, 207(11), 1454 - 7
Use of antibiotic-impregnated polymethyl methacrylate for treatment of an open radial fracture in a horse; Schneider RK et al.; An open, contaminated, comminuted fracture of the radius of a 500-kg adult horse was diagnosed . Antibiotic-impregnated polymethyl methacrylate implants were placed into the fracture site to help eliminate infection from the limb . Later in the course of treatment, lag screws were placed across the fracture to generate compression and healing . The fracture healed, and the horse was released to its owners . The implants were not removed, and only a mild lameness existed 90 days later.

Arch Surg, 1995 Dec, 130(12), 1321 - 8; discussion 1328-9
Antibiotic pharmacokinetics following fluid resuscitation from traumatic shock; McKindley DS et al.; OBJECTIVE: To describe the pharmacokinetic profile of aztreonam and vancomycin hydrochloride in a clinically relevant experimental model of hemorrhagic shock and trauma . METHODS: Ten mongrel pigs (mean +/- SD weight, 26.7 +/- 6.4 kg) were anesthetized with fentanyl citrate and ventilated, and an indwelling catheter was placed in the jugular vein . On day 3, all pigs were subjected to fentanyl administration, ventilation, soft-tissue injury, and an arterial hemorrhage (mean +/- SD, 40% +/- 8%) . After a 1-hour shock period, baseline hemodynamics were restored by reinfusing shed blood plus twice the shed volume as lactated Ringer's solution . Aztreonam and vancomycin were infused on day 1, after resuscitation on day 3, and on days 4 and 8 . Serial plasma samples were collected for 6 hours after treatment, and differences were compared with analysis of variance . RESULTS: Aztreonam clearance initially decreased with trauma, but subsequently increased by 48% (P < .02) by day 8 . Aztreonam steady-state volume decreased by 34% (P = .05, baseline value vs that on day 8) . Vancomycin clearance was increased between 25% and 52% (P < .001) on days 3, 4, and 8 compared with the baseline value . Vancomycin steady-state volume initially increased with trauma (P = .009), but it subsequently decreased by 29% (P < .001) on day 8 . These data cannot be explained by changes in plasma volume per se because levels of plasma sodium, potassium, chloride, and calcium were within normal reference ranges at all time points . Neither liver nor renal functions were severely impaired because levels of serum urea nitrogen, bilirubin, liver enzymes, creatinine, and plasma proteins were within normal reference ranges . Furthermore, our previous work demonstrated that systemic and splanchnic organ oxygen delivery and demand were near normal immediately after fluid resuscitation and for at least 3 days thereafter; thus, there were probably no major perfusion abnormalities in the liver or kidney . CONCLUSIONS: For at least 5 days after trauma, clearance and steady-state volume of aztreonam and vancomycin are altered . These changes suggest that the interval and magnitude of dosing should be adjusted, relative to the standard recommended dosages of each antibiotic, to maximize their efficacy . Similar studies should be done for other antibiotics.

Am Surg, 1995 Dec, 61(12), 1049 - 53
Antibiotic patterns associated with fungal colonization in critically ill surgical patients; D'Amelio LF et al.; Fungal infections (FI) in surgical patients are increasing; mortality approaches 50 per cent . Prior studies identified factors predicting fungal colonization (FC) including broad spectrum antibiotics (BSA) . This study investigates antibiotic patterns predicting FC . Other risk factors and outcomes are analyzed . A total of 72 consecutive SICU patients receiving > or = 7 days BSA were followed . None received prophylactic antifungals . Input data: Age, APACHE II, surgical procedure, lines, ulcer prophylaxis, TPN duration, antibiotic/antifungal regimen . Outcome data: FC, FI, length of SICU and hospital stay, mortality . A total of 32 patients (44%) developed FC; five (16%) developed FI (P = 0.08) . All infected patients died (P = 0.0002) . FC of GU (25%), respiratory (19%), and GI (19%) tracts were common . Multiple site colonization occurred in 25 per cent of colonized patients . Metronidazole and duration of ventilation predicted FC . APACHE II and TPN duration predicted mortality . Mortality occurred exclusively among patients requiring systemic antifungals . Among BSA, only metronidazole independently predisposed to FC . Other predictors of colonization and mortality agree with prior studies . The high mortality among patients requiring systemic antifungals implies that a more aggressive approach to prophylaxis may be warranted.

Pharm World Sci, 1995 Nov 24, 17(6), 207 - 13
Audit of antibiotic usage in medium-sized general hospital over an 11-year period . The impact of antibiotic policies; McElnay JC et al.; The objective of the present study was to evaluate trends in antibiotic expenditure over an 11-year period (1982-1992) in a 370-bed district general hospital in Northern Ireland and to examine the impact of two separate antibiotic policies on antibiotic usage . A further objective was to examine the attitudes of prescribers to the second policy . Drug utilization review was used to collect information on antibiotic expenditure and usage before and after introduction of separate antibiotic policies in 1985 (not intensively monitored) and 1989 (intensively monitored) . A main questionnaire was used to determine the attitudes of prescribers . The first policy (1985) showed no benefits with regard to the number of antibiotic entities stocked (45 before, 45 after), number of dosage units issued (9.3% increase) or expenditure (33.3% increase) . The 1989 policy led to significant reductions in the number of antibiotic entities stocked (28.9%), number of antibiotics issued (11.9%) and expenditure (6.1%) . Expenditure began to spiral upwards when active monitoring of the second policy was suspended . The majority of prescribers (87.2%) who responded to the questionnaire (56.5% response rate) felt that the 1989 policy made a positive contribution to antibiotic usage in the hospital.

Tidsskr Nor Laegeforen, 1995 Nov 20, 115(28), 3504 - 7
{Proper use of antibiotics--what is that?}; Jensenius M et al.; Antibiotics are one of the cornerstones of modern medicine . During the last 20 years there has been an alarming world-wide spread of multiple-resistant bacteria . One of the main reasons is the overuse of all types of antibiotics, especially broad-spectrum drugs . This paper gives general advice on antibiotic therapy in Norway . We adovcate the use of drugs with little ecological impact, such as the penicillins . Whenever possible, empiric treatment with macrolides, tetracyclines cefalosporines, imipenem and fluoroquinolones should be avoided.

Pharmacoeconomics, 1995 Dec, 8(6), 541 - 50
An assessment of the hidden and total antibiotic costs of four parenteral cephalosporins; Smyth ET et al.; The aim of this study was to compare the hidden costs, and their impact on total antibiotic costs, of ceftriaxone therapy with those of cefotaxime, ceftazidime and cefuroxime in nosocomial infection . The total antibiotic costs of 7-day standard courses of the 4 cephalosporins were compared . The costs were divided into 3 parts: (i) the cost of the drug itself; (ii) the preparation and administration (labour) costs; and (iii) the consumables and waste costs . The latter 2 costs together comprised the hidden cost of an antibiotic course . Hidden costs were higher for cefotaxime, ceftazidime and cefuroxime, which are normally administered 3 times a day, than for ceftriaxone, which is administered once daily . The percentage contribution of hidden costs to total antibiotic costs increased with decreasing antibiotic cost, and were lower with higher dosages of all antibiotics . With cefotaxime, ceftazidime and cefuroxime, and with ceftriaxone at the lower dosage given by bolus intravenous (IV) injection, the labour component of hidden costs exceeded the consumables/waste component . However, when costs were calculated for ceftriaxone administered at the higher dosage by IV infusion, the costs of consumables and waste were greater than the labour costs . Ceftriaxone had the lowest hidden costs of all the antibiotics studied . The total antibiotic cost of low dosage ceftriaxone (1 g per dose) was comparable with that of cefuroxime, and was substantially less than the costs of cefotaxime and ceftazidime . At the high ceftriaxone dosage (2g per dose), the total antibiotic cost of cefuroxime was less than that of ceftriaxone; however, the total antibiotic cost of ceftriaxone remained substantially less than that of cefotaxime or ceftazidime.

J Chromatogr A, 1995 Nov 3, 715(2), 337 - 44
Enantiomeric resolution using the macrocyclic antibiotics rifamycin B and rifamycin SV as chiral selectors for capillary electrophoresis; Ward TJ et al.; Rifamycin B and rifamycin SV belong to the class of macrocyclic antibiotics known as ansamycins . These macrocyclic antibiotics were used as chiral selectors in capillary electrophoresis to enantioselectively resolve a number of chiral compounds . They contain groups capable of providing the types of multiple interactions necessary to achieve chiral recognition between enantiomers . In fact, they appear to be complimentary in the types of compounds they can enantiomerically resolve . Rifamycin B is shown to be enantioselective towards positively charged compounds, while rifamycin SV was enantioselective towards negatively charged solutes . The choice of wavelength for detection significantly affects sensitivity . Monitoring one of the wavelengths which coincide with the absorption minima of the chiral selector enhances sensitivity . Resolution is enhanced by keeping the amount of analyte injected on column as low as possible and it is demonstrated that it is possible to detect as little as 0.1% of one enantiomer in the presence of the other enantiomer using indirect detection.

Acta Pol Pharm, 1995 Nov-Dec, 52(6), 441 - 5
Electrochemical studies of some quinolone antibiotics . Part II . Determination by differential pulse polarography in substance and in pharmaceutical formulations; Warowna-Grzeskiewicz M et al.; Differential pulse polarography was used to study quinolone antibiotics: ciprofloxacin, enoxacin, norfloxacin, ofloxacin and pefloxacin on a mercury electrode . The optimal parameters and background solutions have been chosen . New polarographic method of quinolone determination in pure form and pharmaceutical formulations was found . Statistical analysis of the results obtained showed that proposed method is of good accuracy and precision.

Antibiot Khimioter, 1995 Nov-Dec, 40(11-12), 10 - 5
{Electrocoagulation treatment of sewage in antibiotic production}; Polunina EE et al.; The data on the study of the electrocoagulation treatment of highly concentrated sewage in antibiotic production are presented . Aluminium plates were used as the electrodes . The influence of the anode current density, pH and temperature on the process of the electrocoagulation treatment of the sewage was investigated . The electrocoagulation treatment of the sewage in production of tetracycline, oleandomycin and benzyl-penicillin was shown to be efficient.

J Pharm Biomed Anal, 1995 Nov, 13(12), 1453 - 8
Conductimetric titrimetry for assay of selected antibiotics in non-aqueous media; Kilic E et al.; In this study, a conductimetric titration method is proposed for the determination of some commonly used antibiotics . The conductimetric titration of three antibiotics, namely ampicillin, amoxycillin trihydrate and rifampin, was carried out in acetic acid using perchloric acid as titrant . Ciproflaxacin hydrochloride, however, was titrated after being dissolved in acetic acid containing an excess of mercury(II) acetate . For the titration of netilmicin sulphate, barium acetate prepared in acetic acid was used as titrant . The method was found to be highly accurate and precise, having a relative standard deviation of less than 1.0% for all antibiotics studied . It was also shown that the conductimetric titrimetry could be successfully applied to the assay of commercial preparations containing the above-mentioned antibiotics . The validity of the method was tested by the recovery studies of standard addition to pharmaceuticals and the results were found to be satisfactory.

Drug Saf, 1995 Nov, 13(5), 273 - 80
Adverse reactions to antibiotics: is the patient really allergic?
Boguniewicz M.
Many patients who believe themselves allergic to an antibiotic could in fact be given the suspected drug or a related agent safely . A systematic approach incorporating knowledge of immunopathogenic mechanisms, availability and limitations of diagnostic tests and therapeutic options will lead to successful management of these challenging patients.

Biochem Cell Biol, 1995 Nov-Dec, 73(11-12), 1179 - 85
Recognition determinants for proteins and antibiotics within 23S rRNA; Douthwalte S et al.; Ribosomal RNAs fold into phylogenetically conserved secondary and tertiary structures that determine their function in protein synthesis . We have investigated Escherichia coli 23S rRNA to identify structural elements that interact with antibiotic and protein ligands . Using a combination of molecular genetic and biochemical probing techniques, we have concentrated on regions of the rRNA that are connected with specific functions . These are located in different domains within the 23S rRNA and include the ribosomal GTPase-associated center in domain II, which contains the binding sites for r-proteins L10.(L12)4 and L11 and is inhibited by interaction with the antibiotic thiostrepton . The peptidyltransferase center within domain V is inhibited by macrolide, lincosamide, and streptogramin B antibiotics, which interact with the rRNA around nucleotide A2058 . Drug resistance is conferred by mutations here and by modification of A2058 by ErmE methyltransferase . ErmE recognizes a conserved motif displayed in the primary and secondary structure of the peptidyl transferase loop . Within domain VI of rRNA, the alpha-sarcin stem-loop is associated with elongation factor binding and is the target site for ribotoxins including the N-glycosidase ribosome-inactivating proteins ricin and pokeweed antiviral protein (PAP) . The orientations of the 23S rRNA domains are constrained by tetiary interactions, including a pseudoknot in domain II and long-range base pairings in the center of the molecule that bring domains II and V closer together . The phenotypic effects of mutations in these regions have been investigated by expressing 23S rRNA from plasmids . Allele-specific priming sites have been introduced close to these structures in the rRNA to enable us to study the molecular events there.

Biochem Cell Biol, 1995 Nov-Dec, 73(11-12), 877 - 85
Antibiotic inhibition of the movement of tRNA substrates through a peptidyl transferase cavity; Porse BT et al.; The present review attempts to deal with movement of tRNA substrates through the peptidyl transferase centre on the large ribosomal subunit and to explain how this movement is interrupted by antibiotics . It builds on the concept of hybrid tRNA states forming on ribosomes and on the observed movement of the 5' end of P-site-bound tRNA relative to the ribosome that occurs on peptide bond formation . The 3' ends of the tRNAs enter, and move through, a catalytic cavity where antibiotics are considered to act by at least three primary mechanisms: (i) they interfere with the entry of the aminoacyl moiety into the catalytic cavity before peptide bond formation; (ii) they inhibit movement of the nascent peptide along the peptide channel, a process that may generally involve destabilization of the peptidyl tRNA, and (iii) they prevent movement of the newly deacylated tRNA between the P/P and hybrid P/E sites on peptide bond formation.

Zhonghua Yu Fang Yi Xue Za Zhi, 1995 Nov, 29(6), 331 - 4
{A study on antibiotic abuse in 750 children with acute respiratory infection in Tongxian County of Beijing}; Li H et al.; A study on antibiotic abuse and inappropriate use was conducted in 750 children under five years old with acute respiratory infection (ARI) in Tongxian County, Beijing, based on WHO's ARI Standard Case Management for Young Children, who sought medical care in clinics at county, township, and village levels provided by 100 physicians . Results showed 96.9% of them were defined as antibiotic abuse and 62.9% as inappropriate use . Factors that contributed to antibiotic abuse and inappropriate use were length of medical practice of physicians the ill children consulted, their education level, scores of their knowledge and attitude, their diagnostic skills, purposes for antibiotic use, whether or not to enjoy free medical care by employees' dependents, ill children's degree of fever and self-prescription by parents, and so on.

J Foot Ankle Surg, 1995 Nov-Dec, 34(6), 547 - 55; discussion 594
Hematogenous osteomyelitis of the calcaneus in children: surgical treatment and use of implanted antibiotic beads; Kelsey R et al.; Hematogenous osteomyelitis is a relatively uncommon disorder that may prove elusive to early diagnosis and treatment . Metaphyseal long bones are commonly involved and the calcaneus is rarely affected . A high index of suspicion should be maintained regarding the pediatric patient with pain out of proportion to a minor injury . Delay in the diagnosis of hematogenous osteomyelitis in the pediatric patient can result in irreversible growth disturbances and devastating sequelae . The authors present a typical case history with an unusual postoperative course and a review of the clinical aspects and surgical treatment of hematogenous calcaneal osteomyelitis in a child.

J Ind Microbiol, 1995 Nov, 15(5), 407 - 10
Dependence of nitrogen- and phosphorus-regulation of beta-lactam antibiotic production by Streptomyces clavuligerus on aeration level; Fang A et al.; Interference with beta-lactam production in Streptomyces clavuligerus by ammonium and phosphate ions, normally observed with optimum levels of aeration, was eliminated by restriction of the air supply . Under such a restriction, ammonium slightly stimulated and phosphate markedly stimulated beta-lactam antibiotic production . These are rare examples of 'regulation reversal' by an environmental modification.

Antimicrob Agents Chemother, 1995 Nov, 39(11), 2564 - 6
In vitro and in vivo antibiotic susceptibilities of ELB rickettsiae; Radulovic S et al.; The activities of doxycycline, rifampin, chloramphenicol, and erythromycin against ELB rickettsiae (Rickettsia azadi) were determined by dye uptake and plaque assays . Plaque formation in Vero cells was inhibited by 0.12 microgram of doxycycline per ml . The data presented demonstrate the susceptibility of ELB rickettsiae to commonly used antibiotics for the treatment of rickettsial diseases.

Antimicrob Agents Chemother, 1995 Nov, 39(11), 2387 - 91
MICs of 28 antibiotic compounds for 14 Bartonella (formerly Rochalimaea) isolates; Maurin M et al.; We assessed in vitro the antibiotic susceptibilities of 14 Bartonella isolates of the species B . quintana, B . vinsonii, B . henselae, and B . elizabethae . Columbia agar base supplemented with 5% horse blood was used as the antibiotic assay medium . Bacterial growth could be evaluated within 5 days after incubation of the plates at 37 degrees C in a 5% carbon dioxide atmosphere . The MICs at which 90% of isolates are inhibited (MIC90s) were 0.06 microgram/ml for penicillin G and amoxicillin and 0.25 microgram/ml for ticarcillin and cefotaxime . The MIC90s of oxacillin and cephalothin were 4 and 16 micrograms/ml, respectively . The MIC90s ranged from 1 to 4 micrograms/ml for aminoglycosides . Erythromycin, doxycycline, and rifampin displayed MIC90s of 0.12, 0.12, and 0.25 microgram/ml, respectively . MIC90s were 1 and 5 micrograms/ml for trimethoprim-and sulfamethoxazole, respectively, 64 micrograms/ml for fosfomycin, and 16 micrograms/ml for colistin and vancomycin . The study confirms the high levels of in vitro susceptibility of Bartonella agents to antibiotics.

Res Microbiol, 1995 Nov-Dec, 146(9), 721 - 8
Effects of 5-azacytidine on physiological differentiation of Streptomyces antibioticus; Novella IS et al.; We studied the specificity of the effect of 5-azacytidine, a DNA-methylase inhibitor that impairs Streptomyces differentiation . We showed that this compound did not affect global DNA, RNA or protein biosynthesis in submerged cultures of S . antibioticus ETHZ 7451 . Among individual proteins, enzymes such as alkaline phosphatase and intracellular protease were produced in similar amounts in the presence and absence of this compound . However, the production of extracellular protease was significantly inhibited . Also DNA-methyltransferases were inhibited, indicating that DNA methylation might be involved in the regulation of differentiation . By contrast, elevated levels of the antibiotic rhodomycin resulted when 5-azacytidine was added to the culture medium . In order to determine whether there was a correlation between sporulation and altered enzymatic activities, these activities were analysed in S . antibioticus submerged cultures . Among them, alkaline phosphatase and intracellular protease activities did not show a clear correlation with sporulation . However, high levels of extracellular protease were produced during septation of hyphae . This association between extracellular protease and sporulation suggests a specific inhibitory effect of 5-azacytidine, not only on spore formation, but also on physiological differentiation.

J Antibiot (Tokyo), 1995 Nov, 48(11), 1312 - 9
Base-catalyzed isomerism in elfamycin antibiotics . Structures of ganefromycins epsilon and epsilon 1; Carter GT et al.; The structures of ganefromycins epsilon (2a) and epsilon 1 (2b) have been determined by spectroscopic techniques . The compounds are isomeric deoxygenated precursors of the parent antibiotics ganefromycins alpha and beta . The nature of the isomerism was determined by chemical interconversion experiments and spectroscope analysis to be a change in configuration at C-21 . Evidence is provided for other cases of this type of isomerism in the elfamycin class of antibiotics.

J Antibiot (Tokyo), 1995 Nov, 48(11), 1304 - 11
Antibiotic GE37468 A: a novel inhibitor of bacterial protein synthesis . II . Structure elucidation; Ferrari P et al.; GE37468 A is a novel antibiotic produced by Streptomyces sp . ATCC 55365 . It has molecular mass 1309.48 and formula C59H52O12N14S5 and belongs to the thiazolyl peptide group of antibiotics . The structure was elucidated by 1H and 13C NMR and MS studies on intact molecule and its hydrolysis products . The antibiotic is a highly modified peptide containing a macrocycle and a side chain composed of a thiazole ring and two dehydroalanine units.

J Antibiot (Tokyo), 1995 Nov, 48(11), 1267 - 72
PCR inhibition assay for DNA-targeted antibiotics; Hotta K et al.; DNA amplification by polymerase chain reaction (PCR) should be inhibited if the target for amplification region in the template DNA is nicked or cut . Based on this premise, we established a sensitive and differential assay using PCR to detect antibiotics that act on DNA . After template lambda DNA (10 pg) was incubated with antibiotics (10 approximately 20 ng) at 37 degrees C for 30 minutes in a 5 microliters reaction volume, a PCR assay (10 microliters reaction volume; 25 approximately 30 cycles) was performed under the conditions we modified, resulting in amplification of a 500 bp fragment of lambda DNA which was monitored by agarose gel electrophoresis . Among the several antibiotics examined, the anthracyclines, bleomycin, D-cycloserine and mitomycin C clearly inhibited the PCR amplification reaction, whereas actinomycin D and ofloxacin did not . Preincubation of template DNA in the presence of Fe++ was necessary for bleomycin and cycloserine to exhibit marked inhibition of PCR . Mitomycin C exhibited the inhibition in the presence of DTT and Cu+ . By contrast, non-DNA-acting antibiotics (200 ng) such as aminoglycosides, beta-lactams, and macrolides showed no inhibition . The PCR-amplified fragment from lambda DNA was not degraded by incubation with the antibiotics (20 ng) that inhibited PCR . Furthermore, ethylacetate extracts of the cultured broths of actinomycetes proved to be suitable as samples for this PCR inhibition assay.

J Antibiot (Tokyo), 1995 Nov, 48(11), 1254 - 61
Trichorzins HA and MA, antibiotic peptides from Trichoderma harzianum . II . Sequence determination; Hlimi S et al.; A series of 18-residue antibiotic-antifungal peptides, trichorzins HA and MA, were isolated from Trichoderma harzianum strains exhibiting antagonistic properties against phytopathogenic fungi . The sequences of the nine major pure peptides isolated by HPLC were determined by positive ion FAB-MS data and two-dimensional NMR measurements, including COSY, HOHAHA, ROESY and 1H-13C LRCOSY experiments.

Br J Clin Pract, 1995 Nov-Dec, 49(6), 297 - 300
Use of antibiotics after complex open hand injury; Drew PJ et al.; A prospective study undertaken to examine bacterial contamination at presentation, frequency and type of antibiotic prescribed, and outcome, in 50 patients presenting with hand injuries of varying severity, is reported . Results of a national survey of trends in antibiotic prescribing for similar wounds in plastic surgery units are also recorded . Preoperative swabs cultured normal flora or no growth . Forty-eight patients received antibiotics with little consistency in the agent used, route of administration, or length of treatment . Clinical wound infection occurred in three crush injuries . No significant difference in the numbers of surgeons using antibiotics for clean and crushed injuries of all types was demonstrated . The state of the wound, rather than the tissue damaged, seemed to dictate antibiotic use . In dirty wounds, however, damage to deep structures appeared to be an indication for antibiotics--significantly fewer respondents treated dirty injuries of the skin alone . The authors believe that antibiotic use in open hand injury is of no proven benefit, and that this aspect of hand surgery requires further investigation.

Phytochemistry, 1995 Nov, 40(5), 1373 - 4
NMR characterization of guanine DNA site alkylated by kapurimycin A3, an antitumour antibiotic from Streptomyces sp; Chan KL et al.; The kapurimycin A3-guanine adduct was formed by alkylation of the antitumour antibiotic with d(CGCG)2 . The site of alkylation of the guanine was confirmed by comparative NMR studies with N-7-methyl-guanine in DMSO-d6.

J Bacteriol, 1995 Nov, 177(21), 6126 - 36
Cloning and characterization of a polyketide synthase gene from Streptomyces fradiae Tü2717, which carries the genes for biosynthesis of the angucycline antibiotic urdamycin A and a gene probably involved in its oxygenation; Decker H et al.; A DNA fragment was cloned as cosmid purd8, which encodes a polyketide synthase involved in the production of the angucycline antibiotic urdamycin from Streptomyces fradiae Tu2717 . Deletion of the polyketide synthase genes from the chromosome abolished urdamycin production . In addition, purd8 conferred urdamycin resistance on introduction into Streptomyces lividans TK24 . Sequence analysis of 5.7 kb of purd8 revealed six open reading frames transcribed in the same direction . The deduced amino acid sequences of the six open reading frames strongly resemble proteins from known type II polyketide synthase gene clusters: a ketoacyl synthase, a chain length factor, an acyl carrier protein, a ketoreductase, a cyclase, and an oxygenase . Heterologous expression of the urdamycin genes encoding a ketoacyl synthase and a chain length factor in Streptomyces glaucescens tetracenomycin C-nonproducing mutants impaired in either the TcmK ketoacyl synthase or TcmL chain length factor resulted in the production of tetracenomycin C . Heterologous expression of a putative oxygenase gene from the urdamycin gene cluster in S . glaucescens GLA.O caused production of the hybrid antibiotic 6-hydroxy tetracenomycin C.

J Biol Chem, 1995 Oct 27, 270(43), 25672 - 7
Differential recognition of beta -lactam antibiotics by intestinal and renal peptide transporters, PEPT 1 and PEPT 2; Ganapathy ME et al.; This study was initiated to determine if there are differences in the recognition of beta -lactam antibiotics as substrates between intestinal and renal peptide transporters, PEPT 1 and PEPT 2 . Reverse transcription-coupled polymerase chain reaction and/or Northern blot analysis have established that the human intestinal cell line Caco-2 expresses PEPT 1 but not PEPT 2, whereas the rat proximal tubule cell line SKPT expresses PEPT 2 but not PEPT 1 . Detailed kinetic analysis has provided unequivocal evidence for participation of PEPT 2 in SKPT cells in the transport of the dipeptide glycylsarcosine and the aminocephalosporin cephalexin . The substrate recognition pattern of PEPT 1 and PEPT 2 was studied with cefadroxil (a cephalosporin) and cyclacillin (a penicillin) as model substrates for the peptide transporters constitutively expressed in Caco-2 cells (PEPT 1) and SKPT cells (PEPT 2) . Cyclacillin was 9-fold more potent than cefadroxil in competing with glycylsacosine for uptake via PEPT 1 . In contrast, cefadroxil was 13-fold more potent than cyclacillin in competing with the dipeptide for uptake via PEPT 2 . The substrate recognition pattern of PEPT 1 and PEPT 2 was also investigated using cloned human peptide transporters functionally expressed in HeLa cells . Expression of PEPT 1 or PEPT 2 in HeLa cells was found to induce H(+)-coupled cephalexin uptake in these cells . As was the case with Caco-2 cells and SKPT cells, the uptake of glycylsarcosine induced in HeLa cells by PEPT 1 cDNA and PEPT 2 cDNA was inhibitable by cyclacillin and cefadroxil . Again, the PEPT 1 cDNA-induced dipeptide uptake was inhibited more potently by cyclacillin than by cefadroxil, and the PEPT 2 cDNA-induced dipeptide uptake was inhibited more potently by cefadroxil than by cyclacillin . It is concluded that there are marked differences between the intestinal and renal peptide transporters in the recognition of beta -lactam antibiotics as substrates.

Biochemistry, 1995 Oct 17, 34(41), 13305 - 11
Structural investigation of the antibiotic and ATP-binding sites in kanamycin nucleotidyltransferase; Pedersen LC et al.; Kanamycin nucleotidyltransferase (KNTase) is a plasmid-coded enzyme responsible for some types of bacterial resistance to aminoglycosides . The enzyme deactivates various antibiotics by transferring a nucleoside monophosphate group from ATP to the 4'-hydroxyl group of the drug . Detailed knowledge of the interactions between the protein and the substrates may lead to the design of aminoglycosides less susceptible to bacterial deactivation . Here we describe the structure of KNTase complexed with both the nonhydrolyzable nucleotide analog AMPCPP and kanamycin . Crystals employed in the investigation were grown from poly(ethylene glycol) solutions and belonged to the space group P2(1)2(1)2(1) with unit cell dimensions of a = 57.3 A, b = 102.2 A, c = 101.8 A, and one dimer in the asymmetric unit . Least-squares refinement of the model at 2.5 A resolution reduced the crystallographic R factor to 16.8% . The binding pockets for both the nucleotide and the antibiotic are extensively exposed to the solvent and are composed of amino acid residues contributed by both subunits in the dimer . There are few specific interactions between the protein and the adenine ring of the nucleotide; rather the AMPCPP molecule is locked into position by extensive hydrogen bonding between the alpha-, beta-, and gamma-phosphates and protein side chains . This, in part, may explain the observation that the enzyme can utilize other nucleotides such as GTP and UTP . The 4'-hydroxyl group of the antibiotic is approximately 5 A from the alpha-phosphorus of the nucleotide and is in the proper orientation for a single in-line displacement attack at the phosphorus.(ABSTRACT TRUNCATED AT 250 WORDS)

FEMS Microbiol Lett, 1995 Oct 15, 132(3), 195 - 201
Characterisation of ovine Bordetella parapertussis isolates by analysis of specific endotoxin (lipopolysaccharide) epitopes, filamentous haemagglutinin production, cellular fatty acid composition and antibiotic sensitivity; Porter JF et al.; Isolates of Bordetella parapertussis, recovered from sheep or man, were characterised by reaction with specific anti-Bordetella lipopolysaccharide monoclonal antibodies, production of filamentous haemagglutinin, fatty acid patterns, and antibiotic sensitivity . Generally, the isolates lay within one of four groups, with separation of the ovine isolates into two groups . Reactions with specific monoclonal antibodies against lipopolysaccharide separated the ovine isolates into these two groupings . Analysis of the cellular fatty acid compositions by cluster analysis differentiated between the human and the ovine strains and also showed variation within the ovine isolates . When the production of filamentous haemagglutinin was analysed in an ELISA system, a similar pattern emerged . Varying concentrations of filamentous haemagglutinin (11-429 ng (mg total protein)-1) were extracted from the human isolates and the one group of ovine isolates with no significant protein detected in the other ovine group . These studies demonstrate variation between and within B . parapertussis isolates recovered from two mammalian sources.

J Chromatogr A, 1995 Oct 13, 712(2), 378 - 81
Liquid chromatographic determination of the antibiotic fumagillin in fish meat samples; Fekete J et al.; A procedure for the determination of fumagillin, an antibiotic of Aspergillus fumigatus in fish meat samples, using reversed-phase high-performance liquid chromatography is described . Liquid chromatography was performed on an octadecylsilane column using acetonitrile-water-phosphoric acid solution as mobile phase, with detection at 350 nm . Two different types of sample preparation were developed, clean-up and enrichment, and the limits of quantification were 100 ng/g and 5 ng/g, respectively, in fish meat . The recovery was 75 +/- 3% in the concentration range 100-500 ng/g . To introduce the methodology and demonstrate its usefulness, a practical experiment was performed . Trouts fed with fumagillin were examined for elimination of fumagillin . After 24 h, the concentration was shown to decrease to below 100 ng/g.

J Biol Chem, 1995 Oct 6, 270(40), 23520 - 32
Chemical structure and translation inhibition studies of the antibiotic microcin C7; Guijarro JI et al.; Escherichia coli microcin C7 (MccC7) is an antibiotic that inhibits protein synthesis in vivo . It is a heptapeptide containing unknown modifications at the N and C termini (Garcia-Bustos, J . F., Pezzi, N., and Mendez, E . (1985) Antimicrob . Agents Chemoth . 27, 791-797) . The chemical structure of MccC7 has been characterized by use of 1H homonuclear and heteronuclear (13C, 15N, 31P) nuclear magnetic resonance spectroscopy as well as mass spectrometry (1177 +/- 1 Da) . The heptapeptide Met-Arg-Thr-Gly-Asn-Ala-Asp is substituted at the N terminus by a N-formyl group . The C-terminal substituent consists of the phosphodiester of 5'-adenylic acid and n-aminopropanol (AMPap), which is linked via the phosphorus atom to an amide group, thus forming a phosphoramide . The main chain carbonyl of the C-terminal aspartic acid residue is connected via this amide bond to the modified nucleotide unit . MccC7 and the peptide unit inhibit protein translation in vitro while a synthetic analog of the AMPap substituent is not active . Neither the peptide nor the AMPap molecule has an effect on the growth of MccC7-sensible cells . Our results strongly suggest that the peptide is responsible for MccC7 antibiotic activity while the C-terminal substituent is needed for MccC7 transport . Implications of the structure determined in this work for MccC7 synthesis and mode of action are discussed.

Mol Gen Mikrobiol Virusol, 1995 Oct-Dec, (4), 29 - 35
{Directed search for streptomycetes that are producers of ionophoric antibiotics}; Sverdlova AN et al.; Streptomyces producing ionophore antibiotics were searched for in various natural substrata, such as soil, sea water, and coastline sea mud, in many geographical regions . A total of 393 Streptomyces strains were isolated, 308 of which proved to be capable of producing antibiotics; 135 of these contained water-insoluble antibiotically active substances in the mycelium . Studies by radioindication, spectrophotometry, and potentiometry demonstrated that these partially purified hydrophobic antibiotics possessed ionophore properties . Selectivity to monovalent potassium and ammonium cations seems to be a characteristic feature of hydrophobic antibiotics derived from Streptomyces differing them from other bacteria.

Pharm Res, 1995 Oct, 12(10), 1483 - 7
Transport characteristics of ceftibuten, a new cephaloporin antibiotic, via the apical H+/dipeptide cotransport system in human intestinal cell line Caco-2: regulation by cell growth; Matsumoto S et al.; PURPOSE . The intestinal epithelial cell line Caco-2 possesses the H+/dipeptide cotransport system responsible for uptake of oral cephalosporins . In this study, the transport characteristics of ceftibuten were examined from the viewpoint of cell growth in the Caco-2 cells . METHODS . The uptake of cephalosporins by Caco-2 cell monolayers grown on plastic dishes was measured and analyzed kinetically . RESULTS . The uptake of ceftibuten was increased by lowering pH of the incubation medium and was inhibited by excess dipeptide . The transport activity of ceftibuten was dependent on the duration of analysis revealed that the development of ceftibuten uptake was due to not only a decrease in Km but also to an increase in Vmax value . CONCLUSIONS . The uptake of ceftibuten is mediated by the apical H+/dipeptide cotransport system which is regulated by cell growth and/or differentiation in the Caco-2 cells.

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