Jpn J Pharmacol, 1989 Dec, 51(4), 465 - 73 Studies on the nephrotoxicity of aminoglycoside antibiotics and protection from these effects (7): Effect of latamoxef on binding of tobramycin to brush border membranes isolated from rat kidney cortex; Kojima R et al.; We investigated the effect of latamoxef (LMOX) on the binding of tobramycin (TOB) to brush border membranes (BBMs) isolated from rat kidney cortex by calcium precipitation . The simultaneous treatment with TOB (0.2 mM) and LMOX (10 and 20 mM) to the BBMs fraction (about 250 micrograms protein) significantly inhibited the binding of TOB to BBMs . The addition of the reaction mixture of TOB (0.2 mM) and LMOX (4, 10 and 20 mM) which was preincubated for 3 hr at 37 degrees C, to the BBMs fraction resulted in less binding of TOB to the membranes than that observed in the case of simultaneous treatment with both drugs . Although {14C}-labeled LMOX was taken up by BBMs temperature- and time-dependently, the pretreatment with LMOX showed no obvious differences in inhibition of the TOB binding to BBMs, as compared with the result from simultaneous treatment with both drugs . Additionally, the binding of TOB to the LMOX-treated BBMs that were resuspended in fresh medium after the pretreatment with LMOX for 10 min at 37 degrees C was similar to that of TOB to the non-treated BBMs . These results indicate that LMOX inhibits the binding of TOB to BBMs not by binding to BBMs but by interacting with TOB. J Clin Pathol, 1989 Dec, 42(12), 1255 - 8 Antibiotic resistant fever associated with herpes simplex virus infection in neutropenic patients with haematological malignancy; Baglin TP et al.; The incidence of mucocutaneous herpes simplex virus infection confirmed by culture and occurring during febrile neutropenic episodes was determined in 43 patients with haematological malignancy . The outcome of 72 episodes of neutropenic fever was determined and correlated with the presence or absence of herpes simplex virus (HSV) infection . Twenty four patients had mucocutaneous HSV infection during at least one episode . In 24 episodes in which HSV was isolated only 12.5% of fevers responded to antibiotics and 75% of fevers were otherwise unexplained . Conversely, in 48 episodes of neutropenic fever in which HSV was not isolated 67% of fevers responded to antibiotics and only 8.3% were unexplained . The difference in incidence of antibiotic resistant fever in the two groups was significant . There was, therefore, a strong association between mucocutaneous HSV infection and antibiotic resistant fever in immunosuppressed neutropenic patients . As most HSV infections are the result of virus reactivation, establishing the HSV serological state of patients would identify those at risk of infection and hence those in whom the prophylactic use of acyclovir would be indicated. Ann Emerg Med, 1989 Dec, 18(12), 1339 - 43 Antibiotic therapy of life-threatening infectious diseases in the emergency department; Lauter CB; Initial therapy in acutely ill septic patients is necessarily empiric . Although a specific etiologic infectious diagnosis is rarely made in an acute situation, a treatment decision must be made and must be developed from history, physical examination, and minimal laboratory and roentgen studies . Three life-threatening syndromes are discussed: febrile-neutropenic patients with cancer, immunosuppressed patients with fever and lung infiltrates, and patients with acute community-acquired meningitis. Antimicrob Agents Chemother, 1989 Dec, 33(12), 2101 - 8 Reactivation of peptidoglycan synthesis in ether-permeabilized Escherichia coli after inhibition by beta-lactam antibiotics; Talbot MK et al.; The recovery of peptidoglycan-synthesizing activity after inhibition by beta-lactam antibiotics was investigated in ether-permeabilized cells of Escherichia coli B . Such cells synthesize sodium dodecyl sulfate-insoluble peptidoglycan when provided with UDP-linked precursors and Mg2+ . The ability of beta-lactam antibiotics to inhibit the synthesis of peptidoglycan was correlated with their affinity for penicillin-binding proteins 1A and 1Bs . Penicillin-binding protein 1Bs is thought to be the major peptidoglycan synthetase in E . coli and is a major lethal target for beta-lactam antibiotics . Ether-treated bacteria were preincubated with concentrations of beta-lactams sufficient to completely inhibit peptidoglycan synthesis and then treated with beta-lactamases to inactivate free antibiotic prior to measurement of peptidoglycan synthesis . At 40 min after beta-lactamase treatment, the rate of peptidoglycan synthesis was about 74% of the control rate in cells pretreated with ampicillin, but only 15% of the control in cells pretreated with penicillin G or azlocillin . Reversal of inhibition by several other antibiotics fell between these extremes . When cross-linking of peptidoglycan was measured specifically, reversal of inhibition by ampicillin also occurred more readily than that by penicillin G . Reactivation of peptidoglycan synthesis was not due to de novo synthesis of penicillin-binding proteins since it occurred under conditions that did not allow incorporation of {14C}leucine . We conclude that there is considerable variation in the stability of the inactive acyl enzymes formed between various beta-lactams and penicillin-binding protein 1Bs, with those formed by penicillin G being relatively long-lived. Aichi Gakuin Daigaku Shigakkai Shi, 1989 Dec, 27(4), 1071 - 9 {Two cases of intra-arterial infusion of antibiotics in intractable chronic osteomyelitis of the mandible}; Suzuki A et al.; Two cases of intractable chronic osteomyelitis of the mandible were encountered recently . The first of these was a 51-year-old man who complained of swelling in the right cheek and the mandibular region . The other was a 27-year-old man who chiefly complained of swelling, pain and trisms in the right mandible . Both patients were treated with antibiotics and the osteosclerotic tissue was removed . The antibiotics were injected into the superficial temporal artery using a one-shot technique . Radiographs of the patients taken one to two years after the treatment revealed normal conditions with no signs of recurrence . It appears that this form of treatment is effective in the case of intractable chronic osteomyelitis of the mandible. Ann Trop Paediatr, 1989 Dec, 9(4), 256 - 60 Incidence of multiple antibiotic resistances in organisms isolated from cases of infantile diarrhoea in a Nigerian oral rehydration therapy clinic; Lamikanra A et al.; A total of 247 bacterial isolates were obtained from diarrhoeal patients aged 0-60 months in an oral rehydration therapy clinic in Ibadan and tested for sensitivity to 11 antibiotics using the disc diffusion method . Fifty isolates obtained from apparently healthy age-matched controls were similarly tested . The results show that 6(2.4%) of the isolates obtained from the diarrhoeal children were resistant to all the 11 antibiotics used in the test and that most of the others were resistant to several antibiotics . Similarly, a very considerable percentage of isolates obtained from children in the control group were found to be resistant to several antibiotics . It is therefore apparent that there is a high incidence of multiply-antibiotic-resistant isolates within the sample environment. Biochemistry, 1989 Nov 28, 28(24), 9392 - 8 Hypelcin A, an alpha-aminoisobutyric acid containing antibiotic peptide, induced permeability change of phosphatidylcholine bilayers; Matsuzaki K et al.; Interactions of hypelcin A, an alpha-aminoisobutyric acid containing antibiotic peptide, with phosphatidylcholine vesicles were investigated to obtain information on its bioactive mechanism . The peptide induced the leakage of a fluorescent dye, calcein, entrapped in sonicated vesicles . The leakage rate depended on both the peptide and the lipid concentrations . Analysis of this dependency indicated that the leakage was due to the monomeric peptide and that the membrane-perturbing activity of the monomer was higher for solid distearoylphosphatidylcholine vesicles than for fluid egg yolk phosphatidylcholine vesicles . Hypelcin A also affected the gel to liquid-crystalline phase transition of dipalmitoylphosphatidylcholine multilamellar vesicles . The transition was broadened with a reduced transition enthalpy, suggesting the peptide strongly binds the surrounding lipids to perturb the bilayer lipid packing . A circular dichroism study revealed that the helical content of hypelcin A increases upon membrane binding . We concluded that the monomeric peptide with an increased helical content, complexed with the lipids, perturbs the lipid organization and induces the increased permeability. Mol Cell Biochem, 1989 Nov 23-Dec 19, 91(1-2), 39 - 44 Membrane effects of the polyene antibiotic amphotericin B and of some of its derivatives on lymphocytes; Henry-Toulme N et al.; Amphotericin B (AmB) exhibits immunomodulating properties in mice . In vitro studies on lymphocytes, in relation with these properties, are reported here with AmB and two of its derivatives: the N-Fructosyl (N-Fru AmB) and the N-thiopropionyl (AmBSH) derivatives . Interactions of these molecules with thymocytes, a sensitive cell type, demonstrated that the extent of binding is not a toxicity parameter . In contrast, membrane fluidity changes have been observed and appeared to be related to toxicity . Experiments performed with normal B lymphocytes have shown that Amphotericin B derivatives were more potent polyclonal B cell activators than the parent compound . To go further in the understanding of these events, we have investigated in a B cell line WEHI 231, the changes in intracellular Ca2+ and membrane potential induced by AmB and AmBSH . The two polyenes were shown to induce membrane depolarization but no intracellular Ca2+ increase. Biochem Biophys Res Commun, 1989 Nov 15, 164(3), 1281 - 7 Effect of anthracycline antibiotics on the reconstituted mitochondrial tricarboxylate carrier; Stipani I et al.; The effect of anthracycline antibiotics on the activity of the partially purified and reconstituted tricarboxylate carrier system of the rat liver mitochondria was studied . It was found that the citrate/citrate exchange activity is inhibited by Br-daunomycin and with less potency by doxorubicin, daunomycin, epirubicin and idarubicin . The inhibition of the citrate transport activity is concentration and time-dependent . Cardiolipin protects against the inhibition by Br-daunomycin and the reconstituted citrate transport activity depends upon the ratio of cardiolipin/Br-daunomycin. Clin Ter, 1989 Nov 15, 131(3), 177 - 82 {Bacterial infections in cancer patients without neutropenia . Comparison between 2 antibiotic combinations (aztreonam and oxacillin versus cefoxitin and tobramycin)}; Apice G et al.; In the treatment of infections arisen in neoplastic patients without neutropenia, 2 antibiotic combinations (aztreonam + oxacillin vs tobramycin + cefoxitin), have been compared with regard to therapeutic effectiveness and tolerability . Twenty patients (age: 30-75) have been studied . Tolerability of both combinations was excellent . Results of this study showed a lower percentage of superinfections and a higher percentage of cure in patients treated with the combination aztreonam + oxacillin, even if the data were not statistically significant. Am J Surg, 1989 Nov, 158(5), 435 - 7 Antibiotic irrigation and the formation of intraabdominal adhesions; Rappaport WD et al.; The efficacy of antibiotic peritoneal lavage in the prevention of postoperative infection is controversial . The role of intraperitoneally administered cefazolin and tetracycline in the formation of adhesions was studied in the rodent model . Thirty-two rats were divided into 3 groups . Group 1 underwent midline laparotomy with instillation of 10 ml of normal saline solution . Group 2 and Group 3 underwent the same procedure with instillation of 0.2 percent saline solutions of cefazolin or tetracycline, respectively . Animals were sacrificed after 2 weeks . Intraabdominal adhesions were graded and samples of parietal peritoneum were processed for histologic data . Group 2 and Group 3 had significantly higher adhesion scores compared with Group 1 (p less than 0.001) . Histologic appearance of both antibiotic-irrigated groups showed mesothelial thickening with presence of fibroblasts and collagen . Cefazolin and tetracycline irrigation of the abdominal cavity contributes to the formation of peritoneal adhesions in the rat model. Bioorg Khim, 1989 Nov, 15(11), 1445 - 61 {A promising search for substances, suppressing the development of the human immunodeficiency virus, among natural and semisynthetic antibiotics}; Preobrazhenskaia MN; Perspectives of search, among natural and semisynthetic antibiotics, for inhibitors of different stages of the human immunodeficiency virus replication are discussed . The compounds which inhibit the virus absorbtion, reverse transcription, viral mRNA synthesis, viral protein translation or viral glycoprotein processing are presented. J Clin Periodontol, 1989 Nov, 16(10), 647 - 53 Effect of non-surgical periodontal therapy combined with adjunctive antibiotics in subjects with "refractory" periodontal disease . (I) . Clinical results; Magnusson I et al.; The aim of the present study was to evaluate the clinical effect of non-surgical periodontal therapy with the adjunct of a selected antibiotic in subjects with refractory periodontitis . 10 subjects were selected for the study; all had a history of periodontal surgery, tetracycline therapy, and regular maintenance by a periodontist . Clinical registrations including gingival index, plaque index, presence of bleeding and suppuration, pocket depth, and duplicate measurements of attachment level were performed at baseline and at monthly intervals . When disease activity was detected based on the tolerance method, a bacterial sample was taken from the active site and its susceptibilities to a number of antibiotics were determined . For the selected 10 subjects, Augmentin was the antibiotic of choice . Each subject received 750 mg/day for 2 weeks, during which time a full-month scaling and root planing was performed under local anesthesia . Clinical re-evaluation was performed after 3, 6, 9 and 12 months . At the time disease activity was detected, the average loss of attachment at all active sites was 2.2 mm, and the increase in pocket depth 1.5 mm . At 3 months post-therapy, these sites had regained 2 mm of attachment which remained stable through the 12-month examination . Pocket depths decreased 2.5 mm over the first 6 months and then stabilized . The frequency of all sites that gained 1 mm or more of attachment increased by approximately 10% over the first 9 months following therapy . The frequency of all sites that decreased 1 mm or more in pocket depth increased approximately 15% over the same period.(ABSTRACT TRUNCATED AT 250 WORDS) Antibiot Khimioter, 1989 Nov, 34(11), 853 - 5 {Status of the adenine system of the rat liver after administration of anthracycline antibiotics}; Ermolitskaia GR et al.; Changes in the content and ratio of various components of the adenylate system were followed up in the liver of rats after their exposure to doxorubicin and daunorubicin in the time course of 35 days . The shifts detected in various periods after the exposure must be due to different regulatory mechanisms . By the end of the experiment (on day 35) there was a tendency to normalization of the indices. Antibiot Khimioter, 1989 Nov, 34(11), 849 - 52 {Comparative study of the cytotoxic effects of anthracycline antibiotics on heterotransplants of human breast cancer cultivated in diffusion chambers in vivo}; Krutova TV et al.; Cytotoxic activity of doxorubicin, daunomycin, carminomycin and ruboxyl against 50 human breast cancer heterotransplants in diffusion chambers was studied . The effect was estimated autoradiographically on the 6th or the 7th day of the cultivation after the drug administration in the maximum tolerance doses . The tumors were considered sensitive when the labeling index of their transplants after the treatment appeared to be reduced by 50 or less per cent against the control . The number of the tumors sensitive to all the drugs amounted to 72-80 per cent . 19 tumors were sensitive to 4 antibiotics . 14 and 8 tumors were sensitive to 3 and 2 antibiotics, respectively, and only 1 tumor was sensitive to 1 drug . The sensitivity significantly correlated with the initial labeling index of the primary tumors and their heterotransplants . The results suggested that daunomycin and ruboxyl possessed a high cytotoxic activity close to that of doxorubicin and carminomycin and might be recommended for clinical trials in the treatment of patients with breast cancer. Mikrobiol Zh, 1989 Nov-Dec, 51(6), 79 - 83 {The isolation and characteristics of antibiotic-containing liposomes}; Rotov KA et al.; The results of studies on the incorporation of a number of antibiotics into liposomes and the use of gamma irradiation for sterilization of phospholipid vesicles are presented . The toxicity of hydrochloride tetracyclin in free and liposomal forms is estimated for golden hamster with different methods of administration. Xenobiotica, 1989 Nov, 19(11), 1285 - 95 Metabolism of dihydroergotamine by a cytochrome P-450 similar to that involved in the metabolism of macrolide antibiotics; Delaforge M et al.; 1 . Previous studies have shown that the macrolide antibiotics, such as oleandomycin and erythromycin, enhance their own transformation into a stable metabolite-cytochrome P-450 complex, thus impairing monooxygenase activity . This cytochrome P-450 induced by macrolides is similar to the major form induced in rats by pregnenolone-16 alpha-carbonitrile (PCN) (III A1 isozyme) . 2 . The cytochrome P-450 isozyme induced in rats by PCN or macrolide antibiotics bound dihydroergotamine (DHE) with high affinity and was also capable of metabolizing the drug . However, phenobarbital administration enhanced the metabolism of DHE to a greater extent than would be expected from the levels of the PB-PCNE isoenzyme, indicating that other cytochrome P-450 proteins may also be involved in DHE metabolism . 3 . DHE metabolism was inhibited by macrolide antibiotics both ex vivo and in vitro . The metabolite-cytochrome P-450 complex formed by the antibiotics impairs the metabolism of DHE, so that when the complex is dissociated the metabolic activity is restored . These findings explain the observed clinical interactions between macrolides and other drugs, and such an approach may prove useful in their prediction. J Clin Periodontol, 1989 Nov, 16(10), 621 - 4 Effect of adhesive antibiotic TA on plaque and gingivitis in man; Manor A et al.; The adhesive antibiotic TA was applied to the dento-gingival junction of 8 human volunteers, suffering from moderate to severe gingivitis . 2 diametrically opposed quadrants of the mouth received 4 applications of 0.1 mg TA, while the other 2 quadrants were treated with a placebo and served as controls . The plaque index, gingival index and bleeding index were scored periodically for 2 weeks and in 4 patients for up to 30 days . The TA-treated quadrants showed a rapid decrease in all 3 indices following 2 treatments . A further improvement was observed with the 3rd and 4th treatments . 30 days after the onset of the experiment and 23 days after the last application, the indices were still considerably lower than the initial values. J Biochem (Tokyo), 1989 Nov, 106(5), 794 - 7 Biochemical mechanisms of aminoglycoside cell toxicity . II . Accumulation of phospholipids during myeloid body formation and histological studies on myeloid bodies using twelve aminoglycoside antibiotics; Oshima M et al.; Cultured human skin fibroblasts take up aminoglycoside antibiotics into lysosomes to form myeloid bodies . Gentamicin (GM), one such antibiotic, was taken up until the cellular concentration reached an estimated 64 mM on the 3rd day when cells were incubated with 2 mM gentamicin . The rate of release of intracellular GM was high on the first day of incubation and gradually slowed down over the next 4 d . About 50% of the GM remained in the cells even on longer incubation in GM-free medium, suggesting it may irreversibly bind to cellular components . With myeloid body formation, the cellular phospholipid content increased 1.5 times . Bis(monoacyl-glyceryl)phosphate, which is known as a marker of lysosomal phospholipid, phosphatidylcholine and phosphatidylserine showed 250, 162, and 153% increases, respectively . Sphingomyelin was not accumulated, while lysosomal sphingomyelinase was dramatically inhibited . Of 12 different aminoglycoside antibiotics, paromomycin is the most prominent myeloid body-forming antibiotic . The myeloid body-formation is not directly correlated to human nephrotoxicity . On the other hand, the number of myeloid bodies is well correlated to the affinity to the brush border membrane, suggesting that such aminoglycoside antibiotics are taken up easily through cellular endocytosis . The cytotoxic effects of aminoglycoside antibiotics may be due to by their binding to cellular organelles other than lysosomes. Infection, 1989 Nov-Dec, 17(6), 355 - 9 Survival of Borrelia burgdorferi in antibiotically treated patients with Lyme borreliosis; Preac-Mursic V et al.; The persistence of Borrelia burgdorferi in patients treated with antibiotics is described . The diagnosis of Lyme disease is based on clinical symptoms, epidemiology and specific IgG and IgM antibody titers to B . burgdorferi in serum . Antibiotic therapy may abrogate the antibody response to the infection as shown in our patients . B . burgdorferi may persist as shown by positive culture in MKP-medium; patients may have subclinical or clinical disease without diagnostic antibody titers to B . burgdorferi . We conclude that early stage of the disease as well as chronic Lyme disease with persistence of B . burgdorferi after antibiotic therapy cannot be excluded when the serum is negative for antibodies against B . burgdorferi. Vrach Delo, 1989 Nov, (11), 120 - 1 {The use of antibiotics in outpatient practice}; Mal'tsev VI et al.; The authors describe the tactics of using antibiotics in out-patient conditions . In acute bacterial infection the most adapted to the pathogen and infections focus antibiotic is used . The problem of indication to antibiotic therapy is discussed . Of importance is avoidance of the development of resistant strains . Monotherapy with antibiotics of selective narrow spectrum is advocated . The local use of antibiotics is to be avoided. Pediatr Infect Dis J, 1989 Nov, 8(11), 780 - 7 Anatomic and audiologic sequelae after tympanostomy tube insertion or prolonged antibiotic therapy for otitis media; Pichichero ME et al.; In this study the anatomic and hearing sequelae are characterized for 43 children (86 ears) with recurrent acute otitis media and/or persistent otitis media with effusion who had received three or more tympanostomy tube placements and 46 children (92 ears) managed medically with repeated courses of therapeutic and/or or prophylactic antibiotics . In the surgical group 311 tympanostomy tube surgeries had been performed and in the medical group 1334 episodes of acute otitis media and/or 186 episodes of otitis media with effusion occurred . Tympanosclerosis was found in 6.5% of the medical group ears and 52.3% of the surgical group ears . Tympanic atrophy occurred in 4.3% of the medical group ears and 40.7% of the surgical group ears . The duration of the presence of the tympanostomy tube significantly influenced the tympanic membrane . The presence of middle ear fluid at the time of tube insertion, particularly high viscosity ("glue") fluid, correlated with persisting sclerosis (P less than 0.00001) and reduced tympanic membrane mobility (P less than 0.00001) but not tympanic membrane atrophy (P = 0.94) later . Abnormal hearing, defined as a hearing threshold greater than 20 dB occurred in 9.3 to 18.7% of the surgical ears and in 3.7 to 9.0% of the medical ears depending on the hearing frequency tested . Medical management consisting of recurrent use of therapeutic and/or prophylactic antibiotics was associated with infrequent anatomic and audiologic sequelae . Repeated placement of tympanostomy tubes may be associated with the frequent occurrence of both anatomic and audiologic sequelae. Br Vet J, 1989 Nov-Dec, 145(6), 552 - 7 Antibiotic persistence and tolerance in the lactating sheep following a course of intramammary therapy; Buswell JF et al.; The commercial use of sheep for the production of milk and milk products is attractive to farmers actively diversifying their dairy interests due to the impact of the quota system . As intensification of milking increases, flock sizes will enlarge and the incidence of ovine mastitis will inevitably increase . The pharmaceutical industry and the veterinary practitioner will be required to provide advice and data upon the performance of currently available bovine intramammary preparations for the sheep . This study produces evidence to confirm that one available bovine intramammary preparation, when infused into milking sheep, produced a withholding time approximately three times as long as that defined for the cow . Following a course of three infusions over a period of 24 hours after consecutive milkings, milk was not acceptable for human consumption or for the production of cheese and yoghurts until 136 hours following the final infusion . This situation is likely to be representative of that which will occur with other intramammary products used in the ovine species following infusion with bovine intramammary preparations. Berl Munch Tierarztl Wochenschr, 1989 Nov 1, 102(11), 371 - 4 {The effect of combined antibiotic and immune prophylaxis against atrophic rhinitis on the body weight of swine}; Bilkei G; In a natural outbreak of Atrophic Rhinitis, the weaned piglets were divided into four groups . Group 1 (10 weaned piglets); Their mother was vaccinated with 2 ml Rhinipig i . m . 3 weeks prior to farrowing . The piglets received 0.2 ml each of Pargenta 50 (= 10 mg Gentamycin) k . m . on the third, fifth and seventh days after birth . The piglets were fed a food containing 10 ppm Gentamycin base during the 6 weeks following their weaning . Group 2 (10 weaned piglets); Their mother was vaccinated with 2 ml Rhinipig i . m . 3 weeks prior to farrowing . The piglets received 0.2 ml each of Pargenta 50 (= 10 mg Gentamycin) i . m . on the third, fifth and seventh days after birth . Group 3 (10 weaned piglets); Their mother was vaccinated with 2 ml Rhinipig i . m . 3 weeks prior to farrowing . Group 4 (10 weaned piglets, untreated, experimental control group) . The results were during the growing period (from 12.3 kg to 32-34.9 kg) and during the finishing period (from 32-34.9 kg to 100 kg) evaluated . Group 1 showed significantly better food conversion and daily weight gain in both periods when compared to the other groups . Although the difference of daily weight gain between Group 1 and Groups 2 and 3 where diminished by 4.34% respectively 1.72%. J Trauma, 1989 Nov, 29(11), 1462 - 8; discussion 1468-70 Pharmacokinetic monitoring of nephrotoxic antibiotics in surgical intensive care patients; Reed RL 2nd et al.; An assessment of the dosage regimens prescribed for potentially nephrotoxic antibiotics (amikacin, gentamicin, tobramycin, and vancomycin) was undertaken on surgical intensive care unit patients . In 166 patients, 224 series of blood antibiotic level determinations were obtained . Using individualized pharmacokinetic determinations, the regimens were revised as necessary to provide optimal blood levels . Because of variable volumes of distribution and elimination rates, dosing according to standard clinical guidelines produced significantly lower peaks than did pharmacokinetically determined regimens for gentamicin (p less than 0.005), tobramycin (p less than 0.0001), and vancomycin (p less than 0.05) . Importantly, fewer patients achieved therapeutic levels with the original regimens than with the revised regimens for gentamicin (9% vs . 91%, p less than 0.0005), tobramycin (27% vs . 92%, p less than 0.0001), and vancomycin (30% vs . 69%, p less than 0.0001) . Individualized pharmacokinetic analysis of potentially nephrotoxic antibiotics in critically ill patients is essential if therapeutic, non-toxic levels are to be maintained. J Antibiot (Tokyo), 1989 Nov, 42(11), 1643 - 8 1H and 13C NMR assignments of the thiopeptide antibiotic nosiheptide; Mocek U et al.; The 1H and 13C NMR spectra of nosiheptide have been assigned by use of 2D NMR techniques on unlabeled samples and biosynthetically multiple-labeled samples from stable isotope feeding experiments. J Antibiot (Tokyo), 1989 Nov, 42(11), 1639 - 42 The structure of vacidin A, an aromatic heptaene macrolide antibiotic . II . Stereochemistry of the antibiotic; Sowinski P et al.; On the basis of coupling constants and rotating frame nuclear Overhauser effect spectroscopy of vacidin A methoxycarbonylmethylamide, the stereochemistry of the antibiotic was established . The configuration of the aglycone was determined as (3R,7R,9R,11S,13S,15R,17S,18R,19S,21R, 36S,37R,38S) . The aminosugar constituent of the antibiotic was identified as beta-(D)-mycosamine . The chiral center at C-41 remains to be assigned. J Antibiot (Tokyo), 1989 Nov, 42(11), 1631 - 8 The structure of vacidin A, an aromatic heptaene macrolide antibiotic . I . Complete assignment of the 1H NMR spectrum and geometry of the polyene chromophore; Sowinski P et al.; The constitution of vacidin A, a representative of the aromatic heptaene macrolide antibiotics was established on the basis of 13C and 1H-1H double quantum filtered correlated spectroscopy, rotating frame nuclear Overhauser effect spectroscopy, J-resolved 1H as well as 1H-13C correlation NMR spectra . Geometry of the polyene chromophore was determined as 22E,24E,26E,28Z,30Z,32E,34E. J Antibiot (Tokyo), 1989 Nov, 42(11), 1541 - 6 Novel antifungal antibiotics maniwamycins A and B . II . Structure determination; Takahashi Y et al.; The structures of the new azoxy antibiotics maniwamycins A and B have been determined by means of spectral analyses and chemical studies. J Pharm Pharmacol, 1989 Nov, 41(11), 795 - 6 Transport of cephalosporin antibiotics in rat renal basolateral membranes; Takano M et al.; Transport mechanisms of cephalosporin antibiotics in rat renal basolateral membranes have been studied in isolated membrane vesicles . Uptake of {14C}p-aminohippurate, a typical organic anion, by basolateral membrane vesicles was enhanced when membrane vesicles were preloaded with unlabelled p-aminohippurate (counter-transport) . Cephalosporins such as cephradine, cephalexin, and cefazolin inhibited the counter-transport of {14C}p-aminohippurate, as did unlabelled p-aminohippurate and probenecid . In contrast, cephalexin did not affect the uptake of {3H}tetraethylammonium, an organic cation, by basolateral membrane vesicles . These results suggest that most cephalosporins are transported via organic anion transport systems in rat renal basolateral membranes. Biochem Pharmacol, 1989 Nov 1, 38(21), 3867 - 72 Selective membrane toxicity of aminoglycoside antibiotics in membrane vesicles isolated from proximal renal tubules of the rat; Amacher DE et al.; A considerable body of evidence suggests that the nephrotoxic potential of aminoglycoside antibiotics may be associated with the degree of membrane binding and subsequent membrane damage in the renal tubules . In this study, we isolated functional basolateral and luminal membrane vesicles from rat renal cortex, incubated each membrane type in the presence of 1 mM concentrations of either neomycin, netilmicin, gentamicin, hydroxygentamicin, or amikacin, and monitored the activities of the marker enzymes alkaline phosphatase (ALP) and lambda-glutamyltransferase (GGT) (luminal) or ouabain-sensitive Na+,K+-ATPase (basolateral) to determine if there were any selective drug-related alterations of enzyme activities . While none of the five aminoglycosides had any substantive effect upon enzyme activities of luminal vesicles, all five drugs inhibited the basolateral marker enzyme . Neomycin produced the greatest inhibition, hydroxygentamicin and amikacin the least, and gentamicin and netilmicin were intermediate in the inhibition of the enzyme . These results are in accordance with the known relative nephrotoxicity of these same drugs and indicate the usefulness of isolated renal membrane vesicles for in vitro toxicological studies of novel aminoglycosides. Eur J Clin Microbiol Infect Dis, 1989 Nov, 8(11), 943 - 50 Structure, biochemistry and mechanism of action of glycopeptide antibiotics; Reynolds PE; Glycopeptide antibiotics, including vancomycin and teicoplanin, are large, rigid molecules that inhibit a late stage in bacterial cell wall peptidoglycan synthesis . The three-dimensional structure contains a cleft into which peptides of highly specific configuration (L-aa-D-aa-D-aa) can fit: such sequences are found only in bacterial cell walls, hence glycopeptides are selectively toxic . Glycopeptides interact with peptides of this conformation by hydrogen bonding, forming stable complexes . As a result of binding to L-aa-D-Ala-D-Ala groups in wall intermediates, glycopeptides inhibit, apparently by steric hindrance, the formation of the backbone glycan chains (catalysed by peptidoglycan polymerase) from the simple wall subunits as they are extruded through the cytoplasmic membrane . The subsequent transpeptidation reaction that imparts rigidity to the cell wall is also thus inhibited . This unique mechanism of action, involving binding of the bulky inhibitor to the substrate outside the membrane so that the active sites of two enzymes cannot align themselves correctly, renders the acquisition of resistance to the glycopeptide antibiotics more difficult than that to the majority of the other antibiotic groups. Antibiot Khimioter, 1989 Nov, 34(11), 811 - 3 {Mutagenic effect of mitomycin C on different strains of oleandomycin producer Streptomyces antibioticus}; Tankevich ME et al.; Mitomycin C, a DNA-tropic antibiotic, was shown to have a lethal effect on spore sprouts of two strains of Streptomyces antibioticus, an organism producing oleandomycin . When the time of exposure to the antibiotic increased there was an almost equal decrease in the survival rate . The mutagen action on the morphological variation and antibiotic production of the two closely related strains were diverse due to their genetic differences . The strain isolated after the culture treatment with a chemical mutagen and subjected to a more prolonged maintaining selection showed lower variation with respect to its colony morphology . The other strain isolated after treatment of the culture with high concentrations of its own antibiotic showed lower variation with respect to its antibiotic production property . The shift in the antibiotic production in the direction of the low active variants was characteristic of the both highly productive strains. Vopr Virusol, 1989 Nov-Dec, 34(6), 724 - 7 {Structure-activity relation for rhodomycin-type antibiotics and the inhibition kinetics of single-stranded and double-stranded DNA- and RNA-viruses}; Korting HJ et al.; The antiviral activity of anthracycline antibiotics of rhodomycin group was investigated by two independent methods which determined the infectious units or antigenicity of the viruses . The action of rhodomycin depended on the structure, number, and position of amino sugar in aglycon . The antiviral activity was found to increase in serial order: iremycin--adriamycin--daunomycin--alpha-rubicin--beta-rhodom ycin-- violamycin B I complex by inhibition kinetics determined with adenovirus. Mutagenesis, 1989 Nov, 4(6), 439 - 45 In vitro and in vivo cytogenetic studies of three beta-lactam antibiotics (penicillin VK, ampicillin and carbenicillin); Stemp G et al.; The in vitro and in vivo clastogenic potential of three beta-lactam antibiotics, ampicillin, carbenicillin and penicillin VK, was investigated using cultured human lymphocytes and the rat micronucleus test . Neither ampicillin nor carbenicillin induced significant increases in chromosome damage in vitro up to test concentrations of 10 mg/ml . These results contrast with other published studies on these compounds . Both drugs were also inactive in vivo in the rat micronucleus test, using single- or double-dosing regimens (ampicillin 5 g/kg orally; carbenicillin 500 mg/kg i.m., either dosed once 30 h before marrow preparation, or dosed twice 48 and 24 h before marrow preparation) . In vitro, penicillin VK induced a dose-related increase in chromosome and chromatid gaps and breaks, down to concentrations of 1.25 mg/ml . It is likely that the increase in aberration frequency was partly the result of exposing the cells to increased K+ ion concentration, as similar results were obtained when potassium chloride was evaluated over the same molar concentration range . However, the occurrence of 'ion-mediated' clastogenic effects as reported by other workers, does not fully account for the positive effects obtained with this compound, as clastogenic effects were also observed with penicillin V in this test system at similar test concentrations . It is known that exposure of mammalian cells to extremely high concentrations of beta-lactams can affect DNA polymerase alpha activity . An inhibitory effect upon DNA polymerase alpha resulting in a breakdown in the structural integrity of the chromosomes, is suggested as an additional mechanism of action for penicillin VK.(ABSTRACT TRUNCATED AT 250 WORDS) Eur J Pediatr, 1989 Nov, 149(2), 126 - 9 Fat absorption in premature infants: the effect of lard and antibiotics; Verkade HJ et al.; Fat absorption of an adapted cow's milk formula was studied in a randomized controlled trial involving two groups of 18 premature infants (mean gestational age +/- SD: 33.0 +/- 2.9 weeks, range 26.5-37.5 weeks) . The triglyceride configuration was modified by the use of lard . This modification did not improve the absorption of fat or energy . Also no difference in serum concentrations of cholesterol and triglycerides was found . Growth velocity during the study was similar in both groups . Detailed analysis of the data revealed that in infants who received (parenterally) antibiotics (mainly ampicillin and netilmicin) a higher coefficient of fat absorption (+20%, P less than 0.01) and of energy absorption (+8%, P = 0.03) was found . Based on these results, we find no support for the use of lard in adapted cow's milk infant formulas to improve fat absorption . In studies of fat and energy absorption the effects of antibiotics have to be taken into account. BMJ, 1989 Oct 21, 299(6706), 1003 - 6 Reducing the incidence of infection after caesarean section: implications of prophylaxis with antibiotics for hospital resources; Mugford M et al.; OBJECTIVES--To estimate the cost effectiveness of giving prophylactic antibiotics routinely to reduce the incidence of wound infection after caesarean section . DESIGN--Estimation of cost effectiveness was based, firstly, on a retrospective overview of 58 controlled trials and, secondly, on evidence about costs derived from data and observations of practice . SETTING--Trials included in the overview were from obstetric units in several different countries, including the United Kingdom . The costing study was based on data referring to the John Radcliffe Maternity Hospital, Oxford . SUBJECTS--A total of 7777 women were included in the 58 controlled trials comparing the effects of giving routine prophylactic antibiotics at caesarean section with either treatment with a placebo or no treatment . Cost estimates were based on data on 486 women who had caesarean sections between January and September 1987 . MAIN OUTCOME MEASURE--Cost effectiveness of prophylaxis with antibiotics . RESULTS--The odds of wound infection are likely to be reduced by between about 50 and 70% by giving antibiotics routinely at caesarean section . Forty one (8.4%) women who had caesarean section were coded by the Oxford obstetric data system as having developed wound infection . The additional average cost of hospital postnatal care for women with wound infection (compared with women who had had caesarean section and no wound infection) was estimated to be 716 pounds; introducing routine prophylaxis with antibiotics would reduce average costs of postnatal care by between 1300 pounds and 3900/100 pounds caesarean sections (at 1988 prices), depending on the cost of the antibiotic used and its effectiveness . CONCLUSIONS--The results suggest that giving antibiotics routinely at caesarean section will not only reduce rates of infection after caesarean section but also reduce costs. Proc Natl Acad Sci U S A, 1989 Oct, 86(20), 7672 - 6 Nucleotide-specific cleavage and minor-groove interaction of DNA with esperamicin antitumor antibiotics; Sugiura Y et al.; The cleavage of DNA by esperamicin is greatly accelerated in the presence of thiol compounds . Oxygen and active oxygen-radical scavengers have no significant influence upon DNA strand breakage by esperamicin . The preferential cutting sites of esperamicin are at thymidylate residues, and the frequency of bases attacked (T greater than C greater than A greater than G) is different from that of calicheamicin (C much greater than T greater than A = G), neocarzinostatin (T greater than A greater than C greater than G), or bleomycin (C greater than T greater than A greater than G) . Esperamicin preferentially attacks at T and C bases in oligopyrimidine sequences such as 5'-CTC-3', 5'-TTC-3', and 5'-TTT-3' . In contrast to the preferred sites of cleavage by bleomycin, 5'-GT-3' and 5'-GC-3', the preferred sites of esperamicin-mediated DNA degradation are 5'-TG-3' and 5'-CG-3' sequences . The nucleotide-specific cleavage mode of esperamicin is significantly affected by pretreatment of DNA with netropsin and distamycin A, suggesting that interaction of esperamicin occurs through the minor groove of B-DNA . This is further supported by the asymmetric cleavage pattern to the 3' side on the opposite strand of the DNA . The roles of the fucose-anthranilate moiety and the trisaccharide side chain of esperamicin in DNA binding and base recognition are discussed. J Trauma, 1989 Oct, 29(10), 1356 - 61 Prophylactic antibiotics in trauma: the hazards of underdosing; Ericsson CD et al.; Prophylactic antibiotic regimens in trauma patients may be significantly altered by large fluid shifts and hyperdynamic physiologic responses . We prospectively studied prophylactic amikacin and clindamycin in 150 abdominal trauma patients requiring laparotomy, analyzing the effects of duration of coverage, dosing interval, and dose . No difference in infection rates was noted when 72-hour coverage was compared with 24-hour coverage (19% vs . 21%) . Clindamycin dosed at 1,200 mg every 12 hours achieved acceptable serum concentrations; infection rates were not significantly higher than seen with 600 mg every 6 hours (21% vs . 12%, p greater than 0.05) . High-dose (11 mg/kg) amikacin reduced infection rates in patients with high blood loss (p less than 0.025), high Injury Severity Scores (p less than 0.025), and no colon penetration (p less than 0.005) . These data suggest that high doses are more effective than long courses of antibiotics in reducing infections in trauma patients undergoing laparotomy. J Antibiot (Tokyo), 1989 Oct, 42(10), 1482 - 8 Urdamycins, new angucycline antibiotics from Streptomyces fradiae . VI . Structure elucidation and biosynthetic investigations on urdamycin H; Rohr J; A new angucycline antibiotic has been discovered as a small side product of Streptomyces fradiae (strain Tu 2717), the producer of the urdamycin complex, during screening for biosynthetic relatives of urdamycins C and D . The structure was elucidated after isolation, via strain selection, of a mutant of S . fradiae that produces this new congener in larger amounts . The structure includes a new chromophore containing aglycone that has not been found before among the angucyclines nor as a natural product generally . In urdamycin H (1) the angucycline four-ring system is enlarged by a (p-OH-phenyl)furan moiety and is closely related to urdamycin C (2) . The structure was elucidated by comparison of the physico-chemical data with those of known urdamycins, especially with those of urdamycin C (2), and was confirmed by intensive 2D NMR analysis . Biosynthetic studies showed that tyrosine and not the smaller p-OH-phenylglycine is the precursor of the (p-OH-phenyl)furan moiety. Am J Surg, 1989 Oct, 158(4), 324 - 7 Efficacy of an antibiotic mouthwash in contaminated head and neck surgery; Jones TR et al.; Twelve head and neck cancer patients scheduled to undergo an operation contaminated by entrance into the upper aerodigestive tract were enrolled in a prospective, randomized, double-blinded study to evaluate the efficacy of a preoperative antibiotic mouthwash in reducing oral cavity quantitative bacterial counts and the incidence of postoperative wound infections . The group who received the antibiotic mouthwash had a large reduction in the bacterial counts, whereas the group who received the placebo mouthwash had an increase in the bacterial counts (p = 0.024) . None of the patients who received the antibiotic mouthwash had postoperative complications; two of the five patients who received the placebo mouthwash had postoperative complications. Am Fam Physician, 1989 Oct, 40(4), 157 - 62 Outpatient intravenous antibiotic therapy; Brown RB et al.; Outpatient intravenous antibiotic therapy is a cost-effective modality to shorten hospital stays and provide continued care to patients with infections . The recent availability of tamper-proof pumps that can deliver multiple antibiotics on independently timed regimens will further expand the use of home intravenous antibiotics . Problems with reimbursement remain, and new classes of oral antibiotics may provide alternatives to parenteral medications. Minerva Urol Nefrol, 1989 Oct-Dec, 41(4), 271 - 3 {Early antibiotic therapy following urodynamic examination . Results of a randomized, controlled study}; Tosto A et al.; Forty-three young men from the Italian army underwent urodynamic tests following the diagnosis of enuresis . Of these, 37 were included in an assessment trial to define the rationale for early anti-bacterial therapy following the test . The subjects were subdivided into two groups: one group received 500 mg Cinoxacin b.i.d . for 5 days, and the other group was not treated . The comparison of results revealed a high incidence of irritative disorders in both groups (78.9% of treated subjects and 88.9% of untreated subjects) but the most significant complications were observed in the untreated group (feveret in 27.7% and one case of septic fever) . Early anti-bacterial therapy following standard urodynamic tests therefore seems to be a ration tool in urological practice. Rev Fr Gynecol Obstet, 1989 Oct, 84(10), 699 - 703 {Treatment of upper genital infections in women . Multicenter study of the comparative efficacy and tolerance of an amoxicillin-clavulanic acid combination and of a triple antibiotic combination}; Buisson P et al.; Eighty-two patients with laparoscopically confirmed salpingitis were randomly divided into two groups in a multicentre and prospective trial . Single drug therapy with the amoxicillin-clavulanic acid combination was used in 42 patients (group A) . The other 40 patients were given a combination of penicillin, aminoside and metronidazole (group B) . For each case a secondary prescription for a tetracycline was discussed . Clinical results were comparable in both groups: sooner (at the end of the hospitalization period) in group A: 10 cured, 30 improved and 2 failures against 9 cured, 30 improved in group B . Later (evaluation after 5 to 8 weeks) a relapse was noted in five patients in group A and included one case of angioedema in group B . It is concluded that amoxicillin-clavulanic acid combination is a satisfactory alternative to the penicillin-aminoside-metronidazole combination, especially as it is simpler to use. Indian J Biochem Biophys, 1989 Oct, 26(5), 293 - 5 Effect of anthracycline antibiotics on in vitro transcription of chromatin in a Sarcoma-180 whole cell extract; Panda CK et al.; A soluble extract capable of transcribing Sarcoma-180 chromatin and DNA in a cell-free transcription system was prepared from Sarcoma-180 mouse ascites tumour cells . Incorporation of {3H}UTP into trichloroacetic acid-precipitable fraction is (i) reduced by 50% on removing DNase I hypersensitive sites of chromatin and (ii) inhibited by DNA binding antitumour anthracyclines, suggesting that this cell-free assay represents true transcription of active genes of Sarcoma-180 chromatin . Preparation of this soluble extract from mouse ascites tumour cells thus presents a very convenient way of studying cell-free transcription of active genes of chromatin and effect of antitumour agents on chromatin transcription. J Dent, 1989 Oct, 17(5), 241 - 5 Retrograde root filling using antibiotic-containing, radiopaque, bone cement; High AS et al.; An investigation is reported on the in-vitro behaviour, characteristics and properties of three gentamicin-containing radiopaque bone cements that are considered to be promising retrograde root-filling materials . Three commercially available cements, CMW-1G, CMW-3G and Palacos R with gentamicin were studied with regard to bacteriocidal properties, tissue compatibility in cell culture, and ability to seal tooth cavities as evidenced by dye diffusion . Results were compared and contrasted with those obtained with an amalgam . The antibiotic-containing cements investigated are considered to have some distinct advantages over amalgam when used as retrograde root-filling materials in vitro . Amalgam was found to have poor bacteriocidal properties and poor tissue compatibility but slightly better apical sealing abilities than the cements . No apparent drawbacks were found with the cements. J Neurosci Res, 1989 Oct, 24(2), 338 - 46 Aminoglycoside antibiotics impair calcium entry but not viability and motility in isolated cochlear outer hair cells; Dulon D et al.; Cochlear outer hair cells have been well established as primary targets of the ototoxic actions of aminoglycoside antibiotics . These cells, isolated from the guinea pig cochlea and maintained in short-term culture, were used as a model for evaluating the acute effects of gentamicin on cell viability, depolarization-induced transmembrane calcium flux, and depolarization-induced motile responses . On the basis of morphology and fluorochromasia, the presence of extracellular gentamicin as high as 5 mM did not affect the viability of the cells for up to 6 hr, the longest time tested . Viable cells showed binding of fluorescently tagged gentamicin to their base but excluded the drug from their cytoplasm . In response to {K+}-depolarization, intracellular calcium levels (monitored with the fluorescent calcium-sensitive dye fluo-3) increased from a resting value of 218 +/- 102 nM to 2,018 +/- 1,077 nM concomitant with a cell shortening of 0.7% +/- 1.3% . The depolarization-induced calcium increase was apparently caused by calcium entry into the cell as it was inhibited by the calcium-channel blocker methoxyverapamil and prevented in the absence of extracellular calcium . Both gentamicin and neomycin blocked the {K+}-induced calcium increase at an IC50 of 50 microM . Despite the inhibition of calcium entry the ability of the outer hair cells to shorten under {K+}-depolarization was not impaired; in fact, cell shortening was even more pronounced in the absence of calcium influx (2.6% +/- 1.4%) . This argues effectively against the existence of a calcium-dependent actomyosin-mediated component in {K+}-induced shape changes.(ABSTRACT TRUNCATED AT 250 WORDS) J Am Podiatr Med Assoc, 1989 Oct, 79(10), 500 - 4 Adverse effects of antibiotics; Brown RB et al.; Adverse reactions to antibiotics comprise a number of classes of reactions, including toxicity, side effects, and allergy . Each one of these differs in its implication for treatment of the patient . The authors discuss some of the more common and unusual reactions to antibiotics frequently used in the practice of podiatric medicine. Cancer Biochem Biophys, 1989 Oct, 10(4), 289 - 98 Effect of the superoxide dismutase inhibitor, diethyldithiocarbamate, on the cytotoxicity of mitomycin antibiotics; Pritsos CA et al.; Mitomycin C (MC) and its structural analogs porfiromycin (PM), BMY-25282 and BL-6783 are toxic to EMT6 cells under aerobic and hypoxic conditions . The mitomycin antibiotics are hypothesized to exert cytotoxicity under hypoxic conditions by cross-linking DNA following reductive activation, while aerobic cytotoxicity may involve DNA cross-linking by these agents and/or damage due to the generation of oxygen radicals . Previous findings (Pritsos and Sartorelli, 1986) indicated that the rank order of cytotoxicity for a series of mitomycins was the same as the rank order for the rate of oxygen consumption induced by these agents . As an additional approach to explore the role of oxygen radicals in the aerobic cytotoxicity of the four agents studied, EMT6 cells were treated with the mitomycins in the presence of the superoxide dismutase inhibitor diethyldithiocarbamate (DETC) . DETC, which decreased superoxide dismutase activity in EMT6 cells, increased the cytotoxicity of BMY-25282 and BL-6783 by half an order of magnitude, but did not affect the toxicity of PM or MC to these cells . DNA cross-links, a proposed cytotoxic lesion induced by BMY-25282, however, were not detectably increased in EMT6 cells exposed to this agent in the presence of DETC in spite of the large increase in cytotoxicity under these treatment conditions . No single strand breaks were detected in cells exposed to either BMY-25282 or BMY-25282 plus DETC . The findings support the concept that oxygen radicals may have a role in the aerobic cytotoxicity of some of the mitomycin antibiotics, and that the lesions responsible for cytotoxicity produced by oxygen radicals may not reside entirely at the level of DNA. Immunobiology, 1989 Oct, 179(4-5), 445 - 55 Studies on the immunomodulatory effects of anthracycline antibiotics in mice: effects on immune responses and graft immunogenicity; Eckert R et al.; The immunomodulatory effects of adriamycin, a clinically used tumor antibiotic, were studied . A 5-day course of adriamycin therapy in mice led to a suppression of the primary but not of the secondary humoral response to sheep erythrocytes without significant alterations in peripheral blood leukocyte subsets or lymphocyte subpopulations in the spleen . The delayed type hypersensitivity (DTH) response to ovalbumin or alloantigens was not inhibited . Adriamycin-treated spleen cells were unable to stimulate an allogeneic mixed leukocyte reaction, which shows that antigen presentation is inhibited by this drug . Adriamycin-treated murine skin grafts show a prolonged survival after allotransplantation despite their unimpaired ability to induce DTH . The possible cellular mechanisms of these effects and clinical relevance of adriamycin are discussed. J Antimicrob Chemother, 1989 Oct, 24(4), 551 - 9 Decrease in a constitutive form of cytochrome P-450 by macrolide antibiotics; Miura T et al.; The effects of administration of macrolide antibiotics on cytochrome P-450 in liver microsomes of male rats were investigated . The macrolides tested were those with a 14-membered ring such as oleandomycin, troleandomycin, erythromycin and erythromycin estolate, and those with a 16-membered ring such as rokitamycin, leucomycin and josamycin . Cytochrome P-450-metabolite complex was detected with oleandomycin, troleandomycin, erythromycin and erythromycin estolate, whereas no such effect was observed with rokitamycin, leucomycin and josamycin . The content of uncomplexed cytochrome P-450 in liver microsomes remained unchanged with rokitamycin, leucomycin and josamycin, decreased with troleandomycin and oleandomycin, and increased with erythromycin and erythromycin estolate, indicating that oleandomycin, troleandomycin, erythromycin and erythromycin estolate also affect the amounts of other forms of cytochrome P-450 . The administration of oleandomycin, troleandomycin, erythromycin and erythromycin estolate resulted in a dramatic decrease in the activities of testosterone 2 alpha- and 16 alpha-hydroxylases in liver microsomes . Supporting these results, a marked decrease (more than 75%) in the content of P-450-male, a major constitutive form of cytochrome P-450 in male rats, was noted with oleandomycin, troleandomycin, erythromycin and erythromycin estolate, while the decrease was rather small with rokitamycin and leucomycin . We conclude that the administration of the 14-membered ring macrolides may affect drug and steroid metabolism not only by formation of P-450-metabolite complex but also by decrease in the content of P-450-male. J Antimicrob Chemother, 1989 Oct, 24(4), 485 - 507 The molecular basis of the inhibitory activities of type A and type B synergimycins and related antibiotics on ribosomes; Di Giambattista M et al.; Synergimycins A and B act synergistically in vivo; the mixture of the two compounds is more powerful than the individual components and their combined action is irreversible . Type A (virginiamycin M, VM-like) components inactivate the donor and acceptor sites of peptidyltransferase, thus interfering with the corresponding functions of the enzyme . They block two of the peptide chain elongation steps: aminoacyl-tRNA (AA-tRNA) binding to the A site of ribosomes, and peptide bond formation with peptidyl-tRNA (pep-tRNA) at the P site . A tight (non-exchangeable) linkage of tRNA derivatives with the two ribosomal sites requires a stable interaction of their aminoacyl component with peptidyltransferase . Such interaction is prevented by VM, hence the release of AA-tRNA from the A site and of pep-tRNA from the P site upon translocation; ultracentrifugally unstable particles (60S) are thus formed . A new model for peptidyltransferase has been proposed, to account for the interference of VM with the two sites of the enzyme . The action of this antibiotic is partly due to its presence on the ribosome, and partly to the conformational alterations triggered by its binding . Type B synergimycins (VS-like) and the related 14-membered macrolides (erythromycin) have a more complex action, as revealed by copolymer-based models of cell-free protein synthesis . These antibiotics produce an inhibition of peptide bond formation, and a release of incomplete peptide chains, which processes are both template-dependent (i.e . linked to the polymerization of basic amino acids and proline) . The functional interference of VS with peptidyltransferase is explained by the location of the corresponding binding site at the base of the central protuberance of 50S subunits . When ribosome.VS complexes are incubated with erythromycin, the former antibiotic is replaced by the latter; such a replacement does not occur in the presence of VM, which reduces ribosome affinity for macrolides and increases that for type B synergimycins . A study of these complex ribosomal interactions by stopped-flow spectrofluorimetry had allowed a mapping of the binding sites for the MLS antibiotics (macrolides, lincosamides, type B synergimycins) within the peptidyltransferase domain . The active component of these binding sites is represented by segments (loop V and domain II) of 23S rRNA, as indicated by protection and mutation mapping experiments, L proteins increasing the affinity of fixation and its specificity. Biochim Biophys Acta, 1989 Sep 21, 1009(1), 39 - 46 Analysis of the reversible binding of virginiamycin M to ribosome and particle functions after removal of the antibiotic; Nyssen E et al.; Type A synergimycins (VM) were shown to act catalytically and to induce two ribosomal alterations: (a) inability to promote polypeptide synthesis; (b) high-affinity binding of type B synergimycins (VS) . A claim for irreversible binding of type A synergimycins to ribosomes has promoted the present reinvestigation . Submission of ribosomes from VM-treated bacteria to a purification procedure (supposed to remove the drug, according to a low association constant previously reported) yielded particles still holding residual VM . The formation of VM.ribosome complexes, more stable than previously inferred but without covalent linkage, was deduced from the extractability of complexed VM by organic solvents . Moreover, incubation of these complexes with increasing amounts of anti-VM immunoglobulins progressively restored ribosome activity in protein synthesis . Binding of VS to ribosomes, by fluorimetric titrations in the presence of substoichiometric concentrations of VM, was incompatible with catalytic action of type A synergimycins . Ribosomes from VM-treated bacteria displayed also a higher affinity for VS than did control ribosomes . This property did not disappear when ribosome.VM complexes were incubated with anti-VM IgG, nor when VM-IgG complexes were withdrawn from the reaction mixture by protein A-agarose binding . We can conclude that VM binding produces: (1) an inhibition of ribosome-promoted peptide bond formation, which occurs only in the presence of the drug; and (2) an increase of ribosome affinity for VS, which lasts after VM removal . The linkage of this drug with ribosomes is tight but reversible and its action is stoichiometric. Vet Rec, 1989 Sep 9, 125(11), 301 - 3 Antibiotic persistence and tolerance in the lactating goat following intramammary therapy; Buswell JF et al.; Due to the impact of the dairy quota system, the commercial use of goats for the production of milk and associated products is attractive to farmers diversifying their dairy interest . Intensification of milking and the expansion of herds will inevitably increase the incidence of caprine mastitis . The pharmaceutical industry and the veterinary surgeon will be required to provide data and advice upon the performance of currently available bovine intramammary products when used in the goat . This study produced evidence that one available bovine intramammary product, when infused into the glands of milking goats, produced a withholding time approximately double that defined for the cow . Following a course of infusions after three successive milkings, milk was not available for human consumption or for the production of cheese and yoghurt until 112 hours after the final infusion . This situation is likely to be representative of that which will occur for other currently available bovine intramammaries when prescribed in the goat. J Antibiot (Tokyo), 1989 Sep, 42(9), 1370 - 8 Studies on a new herbicidal antibiotic, homoalanosine; Fushimi S et al.; Homoalanosine having a herbicidal activity was isolated from the culture filtrate of a soil isolate SC-1688 which was classified as Streptomyces galilaeus . The chemical structure of homoalanosine was determined to be L-2-amino-4-nitrosohydroxyaminobutyric acid by analyses of spectral and biological data . The antibiotic has high herbicidal activity at low concentrations against especially common cocklebur and ladysthumb among the tested weeds and crops . Foliar application of this antibiotic inhibited the growth of roots and buds . This result indicated that homoalanosine had a systemic herbicidal activity. J Antibiot (Tokyo), 1989 Sep, 42(9), 1339 - 43 Novel antitumor antibiotic phospholine . 2 . Structure determination; Ozasa T et al.; Phospholine, an antitumor antibiotic, has the molecular formula of C25H40NO8P and possesses a delta-lactone and a phosphoric acid ester as functional groups . Its structure was determined based on interpretation of fast atom bombardment MS, 1H NMR, 13C NMR, 1H-1H correlation spectroscopy (COSY), 13C-1H COSY, heteronuclear multiple bond correlation spectroscopy, elemental analysis and chemical modifications. Am J Obstet Gynecol, 1989 Sep, 161(3), 568 - 72 Short course of antibiotic therapy in treatment of postpartum endomyometritis; Morales WJ et al.; To evaluate the safety and efficacy of an abbreviated course of antibiotic therapy in postpartum endomyometritis, 109 patients with endomyometritis were randomized to three study groups . All were treated with clindamycin and tobramycin until afebrility and clinical signs of disease were absent . Patients in group I received antibiotics for greater than or equal to 24 hours, group II received therapy for greater than or equal to 48 hours, and group III received antibiotic therapy for greater than or equal to 48 hours that preceded a 7-day course of oral Augmentin . The groups were similar in size and in demographic and clinical parameters . Two patients from each group required a third antibiotic, and no patient required rehospitalization . Group III required more days of antibiotic therapy than did group I, 2.9 versus 2.1 days (p less than 0.01), and cost $412.00 more per patient . This data strongly suggest that a short course of antibiotic therapy is efficacious and safe and would result in substantial monetary savings. Spine, 1989 Sep, 14(9), 1025 - 32 Iatrogenic discitis: the role of intravenous antibiotics in prevention and treatment . An experimental study; Fraser RD et al.; The role of antibiotics in the treatment of iatrogenic discitis remains controversial . This study was carried out to assess the ability of cephazolin (a first-generation cephalosporin) to penetrate the intervertebral disc and to establish the role of intravenous antibiotics in the prevention and treatment of iatrogenic discitis . Six sheep had 1 g of intravenous antibiotic administered between 30 minutes and 120 minutes before being killed . Two adjacent lumbar intervertebral discs were harvested and assayed for antibiotic concentration . Cephazolin could only be detected in the animals killed at 30 minutes . Intravenous cephazolin was administered 30 minutes before bacterial inoculation in 46 discs of nine sheep . In five animals, the bacterial suspension contained radiographic contrast and, in four sheep, reconstituted chymopapain . No evidence of discitis was found at any level at death . Eight sheep were treated with intravenous cephazolin commencing 1, 2, or 3 weeks after bacterial intradiscal inoculation and for periods of up to 21 days . All discs developed discitis, and the lesions appeared to be similar, irrespective of time between inoculation and the commencement, duration, and dosage of antibiotic therapy . Our study supports the use of a suitable broad-spectrum antibiotic during any surgical procedure that invades the intervertebral disc . Antibiotics, however, are unable to arrest the progression of discitis once it is established Genetika, 1989 Sep, 25(9), 1705 - 7 {Resistance of yeasts to polyene antibiotics}; Kamilova TA et al.; The strains of Saccharomyces cerevisiae yeast with mutations in two genes NYS3 NYS4 were obtained by tetrad analysis . Sterol fraction of these mutants contains two sterols: ergosta-7-en-3 beta-ol (fungisterol) and ergosta-7,24-dien-3 beta-ol (episterol) . The findings allowed to testify the sequence of the ergosterol biosynthesis reactions . Dehydrogenization of the sterol nucleus in C5(6) which is controlled by gene NYS3 occurs simultaneously with the introduction of double bond in C22(23) site of the side chain regulated by gene NYS4. Kardiologiia, 1989 Sep, 29(9), 64 - 7 {Comparative evaluation of the cardiotoxic effects of antineoplastic antibiotics adriamycin and pharmorubicin}; Valvere VIu et al.; Thirty patients with Grade III breast cancer, a locally common form, were examined to compare the magnitude of the cardiotoxic effects displayed by the antitumor anthracyclic antibiotics adriamycin (15 patients) and pharmorubicin (15 patients) . Clinical symptoms of cardiotoxicity developed in 13.3% of the pharmorubicin-treated and in 40% of the adriamycin-treated patients . Among the noninvasive techniques, electrocardiography turned out to be more informative, which enabled the signs of myocardial dystrophy and cardiac arrhythmias to be identified in 20 and 40% on pharmorubicin and adriamycin, respectively . Poly- and echocardiography proved to be less informative than it was shown by the data available in the literature, which is associated with the use of relatively small total doses of anthracycline in our investigations. EMBO J, 1989 Sep, 8(9), 2727 - 36 Analysis of the nucleotide sequence of the Streptomyces glaucescens tcmI genes provides key information about the enzymology of polyketide antibiotic biosynthesis; Bibb MJ et al.; Key information about the biosynthesis of polyketide metabolites has been uncovered by sequence analysis of the tetracenomycin C polyketide synthase genes (tcml) from Streptomyces glaucescens GLA.0 . The sequence data revealed the presence of three complete open reading frames (ORFs) . ORF1 and ORF2 appear to be translationally coupled and would encode proteins containing 426 and 405 amino acids, respectively . The two deduced proteins are homologous to known beta-ketoacyl synthases . ORF3 begins 70 nucleotides after the stop codon of ORF2 and would code for an 83 amino acid protein with a strong resemblance to known bacterial, animal and plant acyl-carrier proteins (ACP) . The presence of an ACP gene within the tcm gene cluster suggests that different ACPs are used in fatty acid and polyketide biosynthesis in Streptomyces . We conclude from these data and earlier information that polyketide biosynthesis in S . glaucescens, and most likely in other bacteria, involves a multienzyme complex consisting of at least five types of enzymes: acylCoA transferases that load the acyl and 2-carboxyacyl precursors onto the ACP; a beta-ketoacyl synthase that, along with the acylated ACP, forms the poly-beta-ketoacyl intermediates; a poly-beta-ketone cyclase that forms carbocyclic structures from the latter intermediates; a beta-ketoacyl oxidoreductase that forms beta-hydroxyacyl intermediates or reduces ketone groups in fully formed polyketides; and a thioesterase that releases the assembled polyketide from the enzyme. J Antimicrob Chemother, 1989 Sep, 24(3), 407 - 13 Pharmacokinetic evaluation of beta-lactam antibiotics; Derendorf H; A simple method is proposed to predict free tissue concentrations of beta-lactam antibiotics from their plasma concentrations after iv bolus injection . During the elimination phase these free tissue concentrations exceed corresponding free plasma concentrations by a constant compound specific factor . This factor can be calculated from the different volumes of distribution (Vc, Vdss and Vdarea) and the plasma protein binding . Calculation of free tissue concentrations allows more secure interpretation of pharmacokinetic data with respect to in-vitro MICs for the comparison of different antibiotics or of the same antibiotic in different patient populations. Infect Dis Clin North Am, 1989 Sep, 3(3), 507 - 16 Antibiotic use in the elderly . A selective review; Gleckman RA; There are unique challenges for the physician who prescribes an antibiotic to an elderly patient . Advanced age is associated with physiological alterations and a reduction in the excretion of numerous compounds . Mental and physical illness in aged patients will impair unsupervised drug compliance . Antibiotic-related adverse events and antibiotic-associated drug interactions pose a threat to life and impede the desired therapeutic outcome. Actual Odontostomatol (Paris), 1989 Sep, 43(167), 433 - 48 {Pharmacokinetics and antibiotic therapy of the child}; Sixou JL et al.; Pharmacokinetics is too often unknown while ordering antibiotics, particularly to children . The aim of that paper is to recall the pharmacokinetic characteristics of the most ordered families in pediatric dentistry: penicillin A and macrolides, as well as the modifications peculiar to children, due to pathology, or subsequent to drug interactions. Ceylon Med J, 1989 Sep, 34(3), 131 - 3 Halitosis and abuse of antibiotics . Report of a case; Ogunwande SA; A case of halitosis caused by the abuse of antibiotics is presented . The abuse of tetracycline resulted in a black hairy tongue and halitosis in this patient . Periodontal therapy and the withdrawal of tetracycline corrected these problems . This is the first patient with halitosis due to abuse of tetracycline seen in our clinic. Vestn Khir Im I I Grek, 1989 Sep, 143(9), 40 - 4 {Endolymphatic administration of antibiotics in the complex treatment of postoperative abscesses in the abdominal cavity}; Zubarev PN et al.; The endolymphatic administration of solutions of antibiotics in complex treatment of patients with intraperitoneal postoperative abscesses resulted in more rapid attenuation of intoxication, improvement of the general state of the patients and their recovery . No complications of the treatment were noted. Postgrad Med J, 1989 Sep, 65(767), 650 - 2 Attitudes of hospital doctors in Wales to use of intravenous fluids and antibiotics in the terminally ill; Marin PP et al.; Decisions concerning the use of intravenous fluids and antibiotics in terminally ill patients are regularly made by hospital doctors, but there is little record of staff attitudes and current practice in Britain . A questionnaire was therefore distributed to 833 Welsh hospital doctors, citing the case of a hypothetical terminally ill patient and asking questions about medical management . Of the 448 (54%) doctors who replied, 346 (77%) had managed a similar patient recently . Intravenous fluids would be administered by 238 (53%), with 206 of these (87%) resiting the cannula as required and 62 (26%) resorting to a central venous line if there was no alternative . With increasing age and seniority doctors become conservative in their approach . Nearly all claimed that 'ensuring the patient's comfort' was the reason for their decision . Only 72 (16%) would use antibiotics if the patient became pyrexial . The results suggest that British doctors are divided in their approach to the medical management of terminally ill patients and there is a need for greater discussion and training so that all the issues involved are fully appreciated. J Nat Prod, 1989 Sep-Oct, 52(5), 1015 - 21 Biosynthesis of elsamicin A, a novel antitumor antibiotic; Lam KS et al.; The 1H noise-decoupled 13C-nmr spectrum of elsamicin A {1} prepared from the cultures of an unknown actinomycete species (ATCC 39417) supplemented with {1-13C}acetate and {2-13C}acetate showed enrichment of all 19-carbons in the aglycone . In addition, L-{methyl-13C}methionine- and D-{1-13C}glucose-supplemented cultures enriched the carbons of the two methyl groups on the disaccharide moiety and the C-1 carbons of the disaccharide, respectively . The results demonstrated that the aglycone of elsamicin A is derived entirely from acetate and the disaccharide portion is biosynthesized from two units of glucose and methionine. Vestn Otorinolaringol, 1989 Sep-Oct, (5), 15 - 20 {Reasons for the use of mydocalm in the prevention and treatment of antibiotic-induced sensorineural hearing loss}; Lantsov AA et al.; The applicability of mydocalm for the prevention and therapy of hypoacusis caused by kanamycin, an antibiotic of the aminoglycoside series, was investigated in animal (guinea-pig) experiments . The changes in nucleic acids and nuclear size of the spiral organ were used as parameters . Hearing loss as shown by the lack of Preyer's reflex developed in response to kanamycin injected at a dose of 50 mg/kg/day for 14 days . In the spiral organ nuclei of hair cells were in the state of functional shrinkage . The use of mydocalm at a dose of 12 mg/kg in parallel with or after kanamycin injection nuclei of receptor cells did not shrink, Preyer's reflex did not disappear (in the case of parallel administration of mydocalm and kanamycin) or recovered (in the case of mydocalm administration after kanamycin injection) . In summary, mydocalm as a vasoactive and neurotrophic drug can be used for the prophylaxis and therapy of hypoacusis caused by aminoglycoside antibiotics and can be recommended for practical application. J Pharm Sci, 1989 Sep, 78(9), 723 - 7 Characterization of the oral absorption of beta-lactam antibiotics . II . Competitive absorption and peptide carrier specificity; Sinko PJ et al.; The beta-lactam antibiotic oral absorption pathway is studied using a single-pass perfusion technique in the rat small intestine . Beta-lactam antibiotic absorption in the presence of amino acids, small peptides, and other beta-lactams is modeled using a simple competitive inhibition boundary condition at the intestinal wall, with a corrected value for the intestinal wall concentration, Cw, derived from the modified boundary layer analysis . The model-predicted permeability in the presence of an inhibitor is used to characterize the beta-lactam antibiotic intestinal carrier system . Several concentrations of cephalexin, coperfused with a constant concentration of cefadroxil (equal to its Km), showed that the Km of cephalexin approximately doubled from 7.2 (+/- 1.1) to 18.8 (+/- 4.1) mM; Jmax remained unchanged at 9.2 (+/- 1.2) and 11.1 (+/- 2.1) mM; and the carrier permeability, Pc, was reduced by approximately 50% from 1.11 (+/- 0.10) to 0.59 (+/- 0.04), consistent with competitive absorption kinetics . The predicted in situ wall permeability, the mean value of P*w, of beta-lactams perfused in the presence of other beta-lactams was calculated and then compared with experimentally determined values . For cefadroxil, P*w = 0.27 (+/- 0.04), the mean value of P*w = 0.29; for cefatrizine, P*w = 0.67 (+/- 0.09), the mean value of P*w (+/- 0.09), the mean value of P*w = 0.59; and for cephalexin, P*w = 0.56 (+/- 0.05), the mean value of P*w = 0.59.(ABSTRACT TRUNCATED AT 250 WORDS) J Pharm Pharmacol, 1989 Sep, 41(9), 628 - 32 Comparison of transport characteristics of amino beta-lactam antibiotics and dipeptides across rat intestinal brush border membrane; Iseki K et al.; The transport characteristics of amino beta-lactam antibiotics, ampicillin and cephradine, have been examined and compared with that of glycylglycine using brush border membrane vesicles isolated from rat small intestine . The initial rate of glycylglycine uptake was markedly stimulated in the presence of an inward H+ gradient compared with the uptake rates in the absence of an H+ gradient . With the same H+ gradient the stimulation of cephradine uptake was lower and ampicillin uptake was not altered . Cephradine uptake, however, was greater than that of glycylglycine in both vesicular conditions ((pH)i greater than (pH)o and (pH)i = (pH)o) . Inhibitory effects of dipeptides, ampicillin and cephradine on the initial uptake of glycylglycine were also examined . Glycylglycine uptake was significantly decreased in the presence of L-phenylalanylglycine or carnosine . Ampicillin and cephradine did not alter the uptake of glycylglycine . These results suggest that the contribution of the inward H+ gradient to the permeation of ampicillin, cephradine and glycylglycine across the rat small intestinal brush border membranes is different for each of the substances examined. Eur J Clin Microbiol Infect Dis, 1989 Sep, 8(9), 783 - 8 In vitro activity of combinations of beta-lactam antibiotics with beta-lactamase inhibitors against cephalosporinase-producing bacteria; Kitzis MD et al.; Combinations of different beta-lactam antibiotics, including cefotaxime, with three beta-lactamase inhibitors were tested against cephalosporinase producing bacterial strains . The most significant antagonism was obtained with a combination of clavulanic acid and cefotaxime, while almost no antagonism was observed with sulbactam and tazobactam . In strains belonging to five different species there was a correlation between the levels of cephalosporinase produced after exposure to different concentrations of inhibitors and the MICs of cefotaxime combined with the same concentrations of inhibitors . It is concluded that there is little likelihood of antagonism between beta-lactam antibiotics and sulbactam or tazobactam. J Pharmacol Exp Ther, 1989 Sep, 250(3), 979 - 84 Transport of imipenem, a novel carbapenem antibiotic, in the rat central nervous system; Suzuki H et al.; The transport of imipenem, a novel carbapenem antibiotic, in the rat central nervous system (CNS) was studied using in vivo, in situ and in vitro experimental techniques . After i.v . bolus administration, the imipenem concentration in the cerebrospinal fluid (CSF) rose to a peak within 30 min and declined with time . The CSF/serum unbound concentration ratio of imipenem was 0.22 at 2 hr after i.v . administration, substantially higher than that reported for benzylpenicillin . By using an in situ brain perfusion technique, we found that imipenem was transported through the blood-brain barrier principally via passive diffusion with a permeability-surface area product comparable to that of mannitol . In vitro, imipenem was accumulated by the isolated choroid plexus via an active organic anion transport system, although much less rapidly than benzylpenicillin . In vivo, after i.c.v . administration, imipenem was cleared from the CNS in a manner comparable to that of mannitol with only a small probenecid-sensitive process . Imipenem thus has minimal affinity for the organic anion transport system in the choroid plexus, resulting in the slow elimination of this drug from the CNS . These results suggest that the difference between imipenem and benzylpenicillin in the ratio of CSF to unbound serum drug concentration is determined principally by the efflux process in the choroid plexus rather than the influx process through the blood-brain barrier. Am J Med, 1989 Sep, 87(3), 301 - 5 Cost-effectiveness of outpatient parenteral antibiotics: a review of the literature; Balinsky W et al.; The results of studies completed on parenteral antibiotic therapy administered in an outpatient setting are reviewed . Although they varied in both size and sophistication, the studies all found that when patients and their families were carefully screened, outpatient therapy was a cost-effective, safe method of administering intravenous antibiotics . The methods used to compare the costs of inpatient and outpatient intravenous antibiotic therapy varied widely . Only direct costs were included in the early comparisons of inpatient and outpatient therapy, whereas the more recent studies included both direct and indirect costs and benefits . All studies found cost savings in the outpatient setting . Unfortunately, very few elderly patients were included because of a Medicare requirement that intravenous antibiotic therapy be administered or supervised by a physician . However, beginning in 1990, the Medicare Catastrophic Coverage Act of 1988 will cover intravenous drugs administered at home . Thus, it will be possible to study applicability of this therapy for the elderly population. J Chromatogr, 1989 Aug 30, 477(2), 259 - 70 Separation of beta-lactam antibiotics by micellar electrokinetic chromatography; Nishi H et al.; The retention behaviour of beta-lactam antibiotics in micellar electrokinetic chromatography (EKC) was investigated . Sodium dodecyl sulphate (SDS) and sodium N-lauroyl-N-methyltaurate were used an anionic surfactants at concentrations of 0.05-0.3 M . It was found that the retention of ionic substances in micellar EKC is determined by the following three factors: the electrophoretic migration of the ionic substances, the interaction between the ionic substances and ionic surfactants and solubilization of the solute by the micellar phase . A difference in the retention behaviours of cationic substances was observed between the two anionic surfactants, which have different groups neighbouring the charge-bearing groups . The effect of an ion-pairing reagent was also investigated to make the effect of the micelle clearer . All test solutes were successfully separated by micellar EKC at SDS concentrations above 0.1 M, with theoretical plate numbers ranging from 70,000 to 260,000. Anal Biochem, 1989 Aug 15, 181(1), 90 - 5 Reductive methods for isotopic labeling of antibiotics; Champney WS; Methods for the reductive methylation of the amino groups of eight different antibiotics using 3HCOH or H14COH are presented . The reductive labeling of an additional seven antibiotics by NaB3H4 is also described . The specific activity of the methyl-labeled drugs was determined by a phosphocellulose paper binding assay . Two quantitative assays for these compounds based on the reactivity of the antibiotic amino groups with fluorescamine and of the aldehyde and ketone groups with 2,4-dinitrophenylhydrazine are also presented . Data on the cellular uptake and ribosome binding of these labeled compounds are also presented. JAMA, 1989 Aug 11, 262(6), 813 - 6 Antibiotic therapy for cat-scratch disease? Bogue CW, Wise JD, Gray GF, Edwards KM. Cat-scratch disease is usually a benign, self-limited disease that causes regional lymphadenopathy . Occasionally, it may present with systemic symptoms and have a prolonged course . To date, antibiotic therapy has not been proved to be of value . We describe three patients with cat-scratch disease who were treated successfully with gentamicin sulfate . Two patients had extensive hepatic involvement, and one patient had regional lymphadenopathy . All three patients responded within 48 hours to intravenous gentamicin . Extensive follow-up has shown no recurrence of symptoms . These cases suggest that gentamicin may be efficacious in shortening the course of cat-scratch disease . Prospective, randomized trials should be performed to confirm these results. N Z Med J, 1989 Aug 9, 102(873), 409 - 11 Antibiotic therapy costs; Atkinson HC et al.; The total cost of antibiotics, rather than acquisition costs alone was estimated . Preparation and administration costs, laboratory and monitoring costs, and labour costs are considered separately for the major antibiotics used within Christchurch Hospital . The oral route of antibiotic administration is by far the cheapest . The cost of infusion therapy compared with an IV push is considerable . This added about +15-+30 in equipment costs and another +20-+30 in labour costs and often constituted over 50% of the total cost of therapy . The cost of adverse reactions and differences in efficacy should ultimately be included but it was impossible to quantitate these factors in terms of absolute costs . Acquisition costs alone are a poor guide to the true costs of therapy . The cost of administering the drug should be considered in the contexts of efficacy, toxicity and impact on the environment . We contend that these considerations should be implied to the overall impact on the hospital budget, rather than the pharmacy costs alone. Hosp Formul, 1989 Sep, 24(9), 513 - 6, 519-20, 523 A multicenter model for examining in vitro susceptibilities of bacteria to antibiotics; Day D et al.; In vitro bacterial susceptibility data are often considered in both hospital formulary and antibiotic prescribing decisions . In this multicenter study, susceptibility data from 105 United States hospitals resulted in a database containing 211,142 isolates for 31 different bacteria and 38 antibiotics . To identify susceptibility patterns of bacteria to antibiotic alternatives, this computerized database was subjected to confidence interval analysis, while controlling for potential sources of random error . This paper describes the multicenter study design and provides several examples of the type of information the analysis can provide to P & Committee members and to practitioners who ultimately must make decisions regarding antibiotic use, sometimes without the benefit of complete hospital-specific historical antibiogram data . Limitations on the interpretation of aggregate in vitro susceptibility data gained from multiple institutions are also discussed. Antimicrob Agents Chemother, 1989 Aug, 33(8), 1286 - 90 Measurement and clinical and pharmacokinetic implications of diffusion coefficients of antibiotics in tissues; Meulemans A et al.; A method for determining diffusion coefficients of four antibiotics in extracellular tissue space according to Fick's law is described . This new method was applied to rat brain tissue and to agar . After diffusion of the antibiotic in one axis, the gradient concentration was determined with microvoltammetric electrodes . These microelectrodes (1 micron at the extreme tip) measured the free diffusible form of electroactive antibiotics in the extracellular brain space . Metronidazole, chloramphenicol succinate, cefsulodin, and piperacillin gave diffusion coefficients ranging from 0.1 x 10(-6) to 0.2 x 10(-6) cm2 . s-1 in tissue; chloramphenicol base, which is positively charged, gave a coefficient of 0.04 x 10(-6) cm2 . s-1 . The coefficient ranged from 0.6 x 10(-6) to 1.2 x 10(-6) cm2 . s-1 in agar . These coefficients were used to simulate antibiotic concentrations in infectious sites and between capillaries by using a simple model of plane diffusion. J Antimicrob Chemother, 1989 Aug, 24(2), 251 - 64 Structural correlations with cross-reactivity of beta-lactam antibiotics in delayed type hypersensitivity . Cross-allergenicity in hypersensitivity to cephems with a tetrazolyl group in the C-3 side chain; Uno K et al.; Cross-reactivity associated with delayed type hypersensitivity (DTH) arising from cephem antibiotics with a tetrazolyl group in the C-3 side chain was investigated by clinical testing and animal experiments . Clinical cross-reaction testing was performed with the leucocyte migration inhibition test (LMIT) with respect to sixteen patients with hypersensitivity induced by cephems with a tetrazolyl group in the C-3 side chain . The proportion of positive LMIT cross-reactions to cephems with a tetrazolyl group in the C-3 side chain was 78% (25/32), to cephems without a tetrazolyl group, 5% (1/22), and to penams, 0% (0/12) . The proportion of positives in tests performed with methyl-tetrazolethiol (MTT) and hydroxyethyl-tetrazolethiol (HTT), which essentially represent the structures of the C-3 side-chains in the allergenic drugs, was 29% (4/14), while the corresponding proportion for 7-aminocephalosporanic acid (7ACA), which represents the skeleton structure of the cephem antibiotics, was 33% (1/3) . The animal experiments were performed with guinea pigs, with latamoxef, cefoperazone and MTT as the sensitizing agents and testing for cross-reactivity by means of delayed type intradermal reactions as well as the LMIT . The results of intradermal testing and the LMIT agreed almost completely, thus providing strong support for the clinical results . Latamoxef and cefoperazone displayed the same cross-reactivity, manifesting cross-reactions with MTT, HTT and 7ACA as well as with cephems having a tetrazolyl group in the C-3 side chain . Moreover, DTH induced by MTT displayed cross-reactivity with cephems possessing tetrazolyl groups in the C-3 side chain . The above results indicate that free MTT radicals, as well as the skeleton ring structure represented by 7ACA, are strongly involved in DTH arising from cephem antibiotics with a tetrazolyl group in the C-3 side chain. J Antimicrob Chemother, 1989 Aug, 24(2), 241 - 50 Application of leucocyte migration tests to detection of allergenic drugs in patients with hypersensitivity to beta-lactam antibiotics; Uno K et al.; In 90 suspected cases of beta-lactam hypersensitivity manifesting exanthema, pyrexia and hepatopathic symptoms, the identities of the allergenic drugs were investigated by immediate type skin reactions, sensitized erythrocyte agglutination tests and leucocyte migration inhibition tests (LMIT) . In addition 30 control patients were tested for hypersensitivity to ampicillin, cephalexin and latamoxef . The control patients manifested the same symptoms as the patients with suspected hypersensitivity to beta-lactam but had not been treated with beta-lactam antibiotics . In the immediate type skin reaction, all the control cases as well as all the suspected beta-lactam hypersensitive patients displayed negative reactions to each of the antibiotics tested . In the sensitized erythrocyte agglutination tests, no antibodies to any of the three drugs were detected in the control group, while antibodies with a titre of 1:2 or more were detected in only 7% (6/90) of the suspected beta-lactam hypersensitive patients . On the other hand, in the LMIT, only 4% (4/90) of the control patients displayed positive reactions to the three test antibiotics, whereas the suspected sensitizing drugs elicited a high rate of positive responses (68/90; 76%) in the group of suspected beta-lactam hypersensitive patients . Broken down into symptomatic categories, response to the LMIT was positive in 41 of 58 cases of suspected drug rash (71%), 26 of 26 cases of suspected drug fever (96%), and 20 of 24 cases of suspected drug-induced hepatopathy (83%) . Thus, the pyrexial group exhibited a particularly high ratio of positive reactions, and in fact exanthemic cases with concomitant symptoms (eosinophilia, pyrexia, hepatopathy, etc.) also displayed a notably high ratio of positives (19/20; 95%) . The overall results indicated that delayed type hypersensitivity (DTH) is largely involved in exanthema, pyrexia and hepatopathy induced by beta-lactam antibiotics, and that the LMIT constitutes an effective means of detecting allergenic drugs in patients with beta-lactam hypersensitivity. Crit Care Med, 1989 Aug, 17(8), 772 - 9 Oxygen consumption and central hemodynamics in septic shock treated with antibiotics, fluid infusions, and corticosteroids; Ottosson J et al.; The multidimensional pathophysiology of septic shock is poorly understood and treatment modalities are controversial . The present study evaluates the relative importance of three therapeutic measures: antibiotics (trimethoprim and sulphamethoxazole {TS}); fluid infusions (lactated Ringer's solution {RL} and 3% albumin {Alb}), and pharmacologic doses of corticosteroids (CS) (dexamethasone {DM}), using central hemodynamics (plasma volume {PV}, cardiac output, oxygen consumption {VO2}), and survival as end-points . Septic shock was induced by intraperitoneal injection of live Escherichia coli bacteria . At 5 h in untreated septic rats, PV had dropped to 76%, cardiac output to 69%, and VO2 to 71% of preshock levels . Untreated septic animals had a mean survival time of 9.7 +/- 1.7 (SD) h, with none surviving 24 h . Regardless of therapy, cardiac output and VO2 at 10 h were predictors of survival time (p less than .01) . Treatment was initiated at 5.5 h after bacterial injection, at a time when TS therapy alone had not improved the 24-h survival rate . Animals treated with DM, RL, and Alb, in this order, exhibited progressively improved central hemodynamics, and 24-h survival rate increased to 60% compared with 0 in untreated animals (p less than .001) . The combination of DM and RL produced no further improvement . However, DM combined with 3% Alb restored VO2, cardiac output, and PV to 81%, 100%, and 125%, respectively, increasing the 24-h survival rate to 97% (29/30), significantly greater than that achieved by any other treatment modality (p less than .05). J Antibiot (Tokyo), 1989 Aug, 42(8), 1294 - 8 A new macromolecular antitumor antibiotic, C-1027 . III . Antitumor activity; Zhen YS et al.; C-1027, a new macromolecular antitumor antibiotic produced by Streptomyces globisporus C-1027, showed extremely potent cytotoxicity toward cultured cancer cells . Compared in terms of IC50 values, antibiotic C-1027 showed much more potent cytotoxicity than doxorubicin, mitomycin C and neocarzinostatin . Spermatogonial assay, a prescreen for anticancer drugs, was highly sensitive for detection of C-1027 . At tolerable doses, C-1027 exhibited marked inhibition on a panel of transplantable tumors in mice, which included leukemia L1210, P388, ascites hepatoma H22, sarcoma 180 and melanoma Harding-Passey. J Med Chem, 1989 Aug, 32(8), 1782 - 8 Brain-specific chemical delivery systems for beta-lactam antibiotics . In vitro and in vivo studies of some dihydropyridine and dihydroisoquinoline derivatives of benzylpenicillin in rats; Wu WM et al.; Four chemical delivery systems (CDS's) based on a dihydropyridine----quaternary pyridinium salt redox system were used for the brain delivery of benzylpenicillin (BP) . CDS's 5 and 9 are diesters of C1 and C2 diols in which one hydroxyl group is esterified by the benzylpenicillin-3-carboxylic group and the other by dihydrotrigonelline . CDS's 13a and 17 are benzylpenicillin esters of amino alcohols in which the amine group is acylated by dihydro-trigonelline (13a) or by 1,2-dihydro-2-methyl-4-isoquinolinecarboxylic acid (17) . In vitro relative stability studies showed that both CDS's and quaternary pyridinium salts were quite unstable in rat and rabbit blood or brain but much more stable in dog or human blood . Kinetic studies performed in rat brain homogenate demonstrated the facile enzymatic oxidation of the CDS's to the corresponding quaternary salts . Hydrolysis of the CDS's and the quaternary salts resulted in the release of benzylpenicillin . In biological media CDS 13a also yielded a water addition product, the 6-hydroxy-1,4,5,6-tetrahydropyridine derivative . In vivo distribution studies were carried out in rats . After iv administration of equimolar doses of BP and CDS's, brain benzylpenicillin levels were found to be substantially higher and more prolonged in case of 5 and 9 than of BP itself . However, administration of 13a and 17 resulted in lower brain benzylpenicillin levels due to the water addition reaction and a nonspecific brain delivery, respectively . The remarkable increase of BP levels as well as the prolonged effect after the administration of 5 and 9 is a result of an improved penetration through the blood-brain barrier of the lipophilic CDS's and a "lock-in" effect of the corresponding quaternary salts generated in situ. J Med Chem, 1989 Aug, 32(8), 1774 - 81 Brain-specific chemical delivery systems for beta-lactam antibiotics . Synthesis and properties of some dihydropyridine and dihydroiosquinoline derivatives of benzylpenicillin; Pop E et al.; Six chemical delivery systems (CDS) were synthesized for benzylpenicillin in order to improve its transport across the blood-brain barrier . The CDS's were based on a dihydropyridine----quaternary pyridinium ion redox system, analogous to the naturally occurring NADH----NAD+ system . Two different types of CDS's were prepared: benzylpenicillin esters of diols in which the other hydroxyl group is esterified by dihydrotrigonelline and benzylpenicillin esters of amino alcohols in which the amine group is acylated by dihydrotrigonelline, or by 1,2-dihydro-2-methyl-4-isoquinolinecarboxylic acid . Lipophilicities of the CDS's were proved to be much higher than those of benzylpenicillin by using Rm values as lipophilicity indexes . Upon oxidation, all of the CDS's gave the quaternary ion forms . Kinetic studies in buffer (pH profiles) indicated that the quaternary salts released benzylpenicillin in pH range of 5-9 via hydrolysis . The CDS's in acidic media yielded as the major reaction product 6-hydroxy-1,4,5,6-tetrahydropyridines as a result of water addition, while in basic conditions benzylpenicillin was released . The water addition reaction was dependent on the CDS's structure, being more prevalent in the case of the "amide-esters" . The dihydroisoquinoline CDS was rather stable in the pH range 5-8. J Chemother, 1989 Aug, 1(4), 261 - 5 Controlled trial of the prophylactic administration of antibiotics in sclerotherapy of esophageal varices; Pulanic R et al.; The aim of this controlled trial was to determine the usefulness of chemoprophylaxis in sclerotherapy of ruptured esophageal varices . Sixty patients bleeding from esophageal varices, without signs of infection at admission, were included in a randomized open trial of one-year duration . Thirty patients received, along with the usual standard therapy (infusions, transfusions) 4x1 g ampicillin intravenously over 3 days, and 30 patients received the standard therapy only . Bleeding varices of the esophagus were sclerosed transendoscopically intravenously using 1% polidocanol solution . Body temperature, general condition, white blood count, differential blood count and sedimentation rate were followed-up over three days . There were no statistically significant differences between the groups in the mean values of the mentioned parameters . There was no correlation between the dose of sclerosant used and body temperature or leukocyte count . Chemoprophylaxis proved to have no effect in this indication. South Med J, 1989 Aug, 82(8), 960 - 2 Efficacy of prophylactic antibiotics for the prevention of endomyometritis after forceps delivery; Heitmann JA et al.; The purpose of this prospective randomized controlled clinical trial was to determine whether prophylactic antibiotics reduce the incidence of endomyometritis after forceps delivery . Of the 393 patients studied, 192 received 2 gm of intravenous cefotetan after forceps delivery, and 201 patients received no antibiotics . There were seven cases of endomyometritis in the group given no antibiotic and none in the cefotetan group, a statistically significant difference (P less than .01) . We conclude that prophylactic antibiotics are effective in reducing the incidence of endomyometritis after forceps delivery . We believe this is the first published study demonstrating this benefit. J In Vitro Fert Embryo Transf, 1989 Aug, 6(4), 236 - 41 Isolation of Mycoplasma bovis from intact and microinjected preimplantation bovine embryos washed or treated with trypsin or antibiotics; Bielanski A et al.; Incubation of day 7 bovine embryos with 10(4) or 10(6) CFU/ml of Mycoplasma bovis (M . bovis) or microinjection of M . bovis into the cells of day 7 embryos did not influence embryonic development . M . bovis was recovered from all embryos washed 10 times by a standard pipetting method or vortexed and pipeted 10 times . M . bovis was also recovered from zonae pellucidae removed and washed from microinjected embryos . Neither treatment with trypsin nor exposure of embryos to combinations of penicillin, streptomycin, lincomycin and spectinomycin, or gentamicin, tylosin, lincomycin, and spectinomycin, inactivated M . bovis. Antibiot Khimioter, 1989 Aug, 34(8), 614 - 20 {Pharmacokinetic monitoring of antibiotic therapy}; Firsov AA; The general strategy in optimization of antibiotic dosage regimens included development of population or common regimens for an "average" patient (the 1st approximation), subpopulation regimens for patients of certain categories on the basis of interactions between the pharmacokinetic parameters and "patient factors" (the 2nd approximation) and individual regimens on the basis of the data of the pharmacokinetic monitoring (the 3rd approximation) . Characteristics of every of the approximations in antibiotic therapy of adults and children were analyzed . Out of the peculiarities of the strategy use in pediatrics+ and micropediatrics+ the following should be indicated: (1) pharmacokinetic heterogeneity of the population requiring grouping of the patients and consequently development of subpopulation dosage regimens omitting stage I, (2) possible development of dosage regimens on the basis of the ration between the pharmacokinetic parameters or immediate drug concentration values and the "patient factors" not only in chronic but also in transitory impairment of some functions and (3) the necessity of considering systematic changes in "pharmacokinetic status" of every child during individualization of the dosage regimens by the data of the pharmacokinetic monitoring. Antibiot Khimioter, 1989 Aug, 34(8), 606 - 9 {Effect of carbohydrates on possible utilization of wastes from antibiotic-manufacturing plants in the construction industry}; Tarakanov OV et al.; Utilization of antibiotic manufacture waste containing a certain amount of carbohydrates in concrete preparation requires their control . It was shown that the content of not more than 0.5 per cent of carbohydrates in the waste had no unfavourable effect on the concrete hardening. Antibiot Khimioter, 1989 Aug, 34(8), 593 - 6 {Effect of the antineoplastic antibiotic bruneomycin on lymphocyte population ratio in mice}; Vatin OE; Data on the quantitative ratio of the populations of T- and B-cells in the lymphoid organs of mice at various periods after oral administration of bruneomycin are presented . It was shown that in contrast to the total number of T- and B-cells in the spleen and mesenteric lymph nodes amounting to the minimal values at the early periods (days 1-3) after the antibiotic injection, their relative content remained rather high . Complete recovery of the number of T- and B-lymphocytes in the above organs was observed only by the end of a month period . Study on the kinetics of the immune response to sheep red blood cells showed that reactivity of the antibody producers in the experiments with bruneomycin increased 1.5-2 fold as compared to the control. J Bacteriol, 1989 Aug, 171(8), 4518 - 20 Induction of ermC methylase in the absence of macrolide antibiotics and by pseudomonic acid A; Kadam SK; The methylase encoded by erm genes and induced by erythromycin modifies the 23S rRNA and confers resistance to macrolide-lincosamide-streptogramin B antibiotics . Induction is due to a posttranscriptional mechanism in which the inducer activates translation of methylase mRNA by binding to unmethylated (erythromycin-sensitive) ribosomes and stalling them in the leader region . It is shown in this study that pseudomonic acid A, an inhibitor of isoleucyl-tRNA synthetase, can also induce methylase synthesis . Isoleucine starvation has a similar effect on ribosomes translating the ermC leader region to cause induction of methylase synthesis . These observations support the requirements for ribosome stalling and destabilization of a stem-loop structure and demonstrate that stalling can occur without macrolide-bound ribosomes. Enferm Infecc Microbiol Clin, 1989 Aug-Sep, 7(7), 349 - 53 {Use of aminoglycoside antibiotics in a general hospital: kinetics consequences in those patients whose blood levels are not monitored}; Saucedo R et al.; A surprise monitoring of plasma aminoglycoside level was carried out in our Hospital in 55 patients . Basal samples and samples one hour after i.m . or i.v . administration were obtained . A protocol sheet with personal, clinical and therapeutic data was fi