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