Antibiot Khimioter, 1991 Oct, 36(10), 26 - 8 {Problems of resistance of the causative agent of melioidosis to antibiotics}; Antonov IuV et al.; It was shown that the pathogen causing melioidosis was highly resistant to antibiotics including beta-lactams . Antibiotic sensitive mutants of P . pseudomallei were isolated after mutagenesis induced by nitrosoguanidine . Permeability for 3H-tetracycline and tetracycline sensitivity of the mutant cells was respectively 3 and 20 times as high as those of the initial parent strain . Gas liquid chromatography revealed quantitative and qualitative changes in separate sugars of the lipopolysaccharide structure in antibiotic sensitive mutants as compared to the initial strain. Biomaterials, 1991 Oct, 12(8), 763 - 6 In vitro studies of elastin-fibrin biomaterial degradation: preservative effects of protease inhibitors and antibiotics; Collet D et al.; The degradability of a new elastin-fibrin material was tested in vitro versus human pancreatic elastase (HPE) and plasmin (PL) activities . It is shown that aprotinine Iniprol, a well-known protease inhibitor and Eglin C, a new potent inhibitor of HPE, especially when used in synergy, efficiently protected the material . A small amount of specific antibiotics was incorporated into the material . The two products will allow the material to be used in digestive surgery with improved safety. Proc Natl Acad Sci U S A, 1991 Oct 1, 88(19), 8860 - 4 An unusual mechanism for resistance to the antibiotic coumermycin A1; del Castillo I et al.; Bacterial DNA gyrases are type II topoisomerases made up of two A subunits and two B subunits . Coumarins are carbohydrate-containing antibiotics that inhibit topoisomerases II by competing with ATP for binding to the enzymes . High resistance to coumarins is produced in bacterial species by mutations in gyrB, the gene encoding subunit B . We have found an unusual mechanism of resistance to coumarins in Escherichia coli . This mechanism is exhibited by cells containing the wild-type gyrB, or its 5' half, in high copy number . Since homologous mutant gyrB (coumermycin resistant) truncated genes did not confer drug resistance at all under the same conditions, we propose that this mechanism of resistance is due to drug sequestration by the overproduced wild-type GyrB polypeptides . A corollary of this is that the amino half of GyrB is required and sufficient to fashion the ATP-binding domain of DNA gyrase, a conclusion that was further supported by mapping three independent coumarin-resistant mutations at Arg-136 of GyrB . Just upstream of this residue there is a glycine-rich sequence highly conserved in all topoisomerases II, which seems to be a good candidate for the actual ATP-binding site. Schweiz Med Wochenschr, 1991 Sep 28, 121(39), 1408 - 12 {Therapy with aminoglycoside antibiotics: once daily (q.d.)?}; Gerber AU; Theoretical and experimental arguments favor administration of aminoglycosides once daily (q.d.) . Results of clinical studies with a limited number of patients support these arguments . However, some practical and clinical questions remain unanswered . Therefore, q.d . infusion of aminoglycosides must still be considered experimental and must remain in the hands of infectious disease specialists until the results of ongoing clinical studies yield the ultimate proof that this novel dosing schedule is as efficacious and no more toxic than the conventional dosing regimens. Nature, 1991 Sep 26, 353(6342), 368 - 70 Antibiotic inhibition of group I ribozyme function; von Ahsen U et al.; The discovery of catalytically active RNA has provided the basis for the evolutionary concept of an RNA world . It has been proposed that during evolution the functions of ancient catalytic RNA were modulated by low molecular weight effectors, related to antibiotics, present in the primordial soup . Antibiotics and RNA may have coevolved in the formation of the modern ribosome . Here we report that a set of aminoglycoside antibiotics, which are known to interact with the decoding region of the 16S ribosomal RNA of Escherichia coli, inhibit the second step of splicing of the T4 phage-derived td intron . Thus catalytic RNA seems to interact not only with a mononucleotide and an amino acid, but also with another class of biomolecules, the sugars . Splicing of other group I introns but not group II introns was inhibited . The similarity in affinity and specificity of these antibiotics for group I introns and rRNAs may result from recognition of evolutionarily conserved structures. Biochemistry, 1991 Sep 24, 30(38), 9242 - 6 Heat-induced DNA cleavage by esperamicin antitumor antibiotics; Uesawa Y et al.; Esperamicin A1 effectively breaks DNA strands upon heating at 50 degrees C . The preferential DNA cutting sites of heat-activated esperamicin A1 are random and clearly differ from those of thiol- or UV-light-mediated DNA breakage with esperamicin A1 . The absence of heat-induced DNA cleavage by esperamicin Z and the induction of the DNA breakage by esperamicin A1 disulfide indicate that (1) the enediyne core plays a significant role in this DNA strand scission and (2) the DNA cutting with the heat-activated esperamicin antibiotics does not necessarily require a trisulfide trigger in the aglycon portion . On the basis of the present results, a probable mechanism for the heat-induced DNA cleavage of esperamicin A1 has been proposed. FEMS Microbiol Lett, 1991 Sep 15, 67(1), 65 - 8 Biological characterization of the lytic cycle of actinophage phi A7 in Streptomyces antibioticus; Diaz LA et al.; Some basic parameters of the lytic development of phage phi A7 in Streptomyces antibioticus are described . One-step growth experiments demonstrated that at 28 degrees C phi A7 has a latent period of about 60 min and an exponential growth period of about 35 min . The average burst size ranged from 70-100 plaque forming units per infected cell . At the same temperature 50% of the virions were adsorbed to germ tubes of S . antibioticus in about 10 min . This corresponds to an adsorption constant of 6.5 x 10(-10) ml/min . The phage was unable to adsorb the host at other stages of the life cycle (spores or mycelium) . Divalent cations are not required for phi A7 stability but Ca2+ proved to be essential for adsorption and also for a later stage of the vegetative development of the phage. BMJ, 1991 Sep 7, 303(6802), 558 - 62 Acute red ear in children: controlled trial of non-antibiotic treatment in general practice; Burke P et al.; OBJECTIVE--To examine the efficacy and safety of conservative management of mild otitis media ("the acute red ear") in children . DESIGN--Double blind placebo controlled trial . SETTING--17 group general practices (48 general practitioners) in Southampton, Bristol, and Portsmouth . PATIENTS--232 children aged 3-10 years with acute earache and at least one abnormal eardrum (114 allocated to receive antibiotic, 118 placebo) . INTERVENTIONS--Amoxycillin 125 mg three times a day for seven days or matching placebo; 100 ml paracetamol 120 mg/5 ml . MAIN OUTCOME MEASURES--Diary records of pain and crying, use of analgesic, eardrum signs, failure of treatment, tympanometry at one and three months, recurrence rate, and ear, nose, and throat referral rate over one year . RESULTS--Treatment failure was eight times more likely in the placebo than the antibiotic group (14.4% v 1.7%, odds ratio 8.21, 95% confidence interval 1.94 to 34.7) . Children in the placebo group showed a significantly higher incidence of fever on the day after entry (20% v 8%, p less than 0.05), mean analgesic consumption (0.36 ml/h v 0.21 ml/h, difference 0.14, 95% confidence interval 0.07 to 0.23; p = 0.0022), mean duration of crying (1.44 days v 0.50 days, 0.94; 0.50 to 1.38; p less than 0.001), and mean absence from school (1.96 days v 0.52 days, 1.45; 0.46 to 2.42; p = 0.0132) . Differences in recorded pain were not significant . The prevalence of middle ear effusion at one or three months, as defined by tympanometry, was not significantly different, nor was there any difference in recurrence rate or in ear, nose, and throat referral rate in the follow up year . No characteristics could be identified which predicted an adverse outcome . CONCLUSIONS--Use of antibiotic improves short term outcome substantially and therefore continues to be an appropriate management policy. Allergy Proc, 1991 Sep-Oct, 12(5), 347 - 50 Multiple antibiotic sensitivity in a pediatric population; Kamada MM et al.; Multiple antibiotic sensitivity (MAS), a common but complex clinical problem, has not been reviewed in the pediatric population . We evaluated 120 children with a history of MAS . The offending antibiotics were beta lactam (186 adverse reactions), sulfonamide (86 adverse reactions), macrolide (32 adverse reactions), erythromycin/sulfisoxazole (26 adverse reactions), aminoglycoside (2 adverse reactions), and tetracycline (2 adverse reactions) . Urticaria occurred in 183 reactions, followed by polymorphous rash (n = 71), angioedema (n = 19), erythema multiform (n = 9), bronchospasm (n = 8), arthralgia (n = 7), serum sickness (n = 4), and laryngeal edema (n = 3), the mean age for the first reaction was 3 years (range 1 month to 13 years) . Adverse reaction to three classes of antibiotics were noted in 22 patients, and two patients were noted to have adverse reactions to four or more antibiotic classes . Skin tests (ST) were performed in 98 children using penicillin G, a commercial benzyl penicilloyl polylysine, a minor determinant mixture, and a beta lactam analog . Positive ST were noted in 26% (31/120) of the MAS patients . Children with a history of MAS are likely to have true IgE-mediated reactions as documented by positive immediate hypersensitivity reactions to penicillin and/or its minor determinants . Therefore, MAS patients should be carefully evaluated for antibiotic sensitivity and not be assumed to have sensitivity to drug formulation as a basis for MAS. J Appl Bacteriol, 1991 Sep, 71(3), 228 - 32 Competitive dominance of antibiotic-producing marine bacteria in mixed cultures; Lemos ML et al.; Competitive relationships between antibiotic-producing marine bacteria and other non-producers were studied in seawater mixed cultures . Producer strains showed a competitive advantage against non-producers as the latter were inhibited after a short time . Inhibition was also noted in mixed cultures of two producer strains . The inhibitory effect was not observed in a mixed culture with two non-producers, which indicates that an amensalist interaction occurred between populations of antibiotic-producing and non-producing marine bacteria . The results suggest that antibiotics could play an important role in the competitive relationships between marine bacterial populations. Can J Microbiol, 1991 Sep, 37(9), 659 - 64 Effect of ultraviolet-induced mutants of Trichoderma harzianum with altered antibiotic production on selected pathogens in vitro; Graeme-Cook KA et al.; Mutants of Trichoderma harzianum with altered antibiotic production were isolated using ultraviolet light mutagenesis . These included strains whose activity in a Fusarium oxysporum spore germination assay was greater than twice that of the parental strain and one that had no detectable antifungal activity . Characterisation of extracellular metabolites of these strains using thin-layer chromatography and gas-liquid chromatography showed that the strains with high activity produced only elevated levels of a 6-n-pentyl pyrone, the antibiotic produced by the parental strain, but two new antifungal compounds . One of these has been identified as an isonitrile antibiotic . The nature of the interactions of the mutants with Fusarium oxysporum, Rhizoctonia solani, and Pythium ultimum was examined in an in vitro dual-plating assay using two media . High antibiotic production by two T . harzianum strains, BC10 and BC63, did increase inhibition of hyphal growth of R . solani and P . ultimum, but there was no correlation between increased antibiotic production and colonisation ability . In some cases the increased antibiotic levels appeared to impede colonisation of F . oxysporum and R . solani by the mutants . Slow growth rate also affected colonising ability . The types of interactions showed great variability depending on the nature of the T . harzianum isolate and on the test fungus. Antimicrob Agents Chemother, 1991 Sep, 35(9), 1937 - 9 Interplay of cell wall barrier and beta-lactamase activity determines high resistance to beta-lactam antibiotics in Mycobacterium chelonae; Jarlier V et al.; We calculated the target access index, which reflects the probability that a drug will reach its target at an effective concentration, and the predictive MICs of cephaloridine, cephalothin, and cefazolin for Mycobacterium chelonae from the drug concentrations inhibiting the binding of benzylpenicillin to penicillin-binding proteins, the permeability coefficients, and the beta-lactamase properties . Despite a low level of beta-lactamase activity and because of a very effective permeability barrier, the target access indices were very low, e.g., 100 times lower than for penicillinase-producing Escherichia coli . The predicted MICs were within one to three twofold dilutions of the experimentally determined values (which ranged between 512 and greater than or equal to 2,048 micrograms/ml) . These results demonstrate that the interplay of the cell wall barrier and beta-lactamase activity determines high resistance of M . chelonae to beta-lactam antibiotics. Antimicrob Agents Chemother, 1991 Sep, 35(9), 1782 - 4 Choice of antibiotic in nonelective cesarean section; Hager WD et al.; The use of antibiotics for prophylaxis against infection among women undergoing nonelective cesarean section has become the standard of care in the United States . Many different antibiotics have been used successfully . Single-dose regimens administered after the cord is clamped have proven just as effective as multiple-dose regimens . Although the most frequently used class of antibiotics is the cephalosporin family, the single best agent has not been determined . This study was a double-blind, randomized trial in which we compared a narrow-spectrum cephalosporin (cefazolin; n = 63) with an expanded-spectrum cephamycin (cefoxitin; n = 66) and with a broad-spectrum cephalosporin (cefotaxime; n = 60) used as a single-dose prophylaxis in patients undergoing a nonelective cesarean section . Of the 194 patients enrolled in the study, 189 were evaluable . There was no significant difference between the groups in mean age, gravidity, parity, duration of labor, duration of ruptured membranes, number of vaginal examinations, or socioeconomic status (socioeconomic status was defined by third-party coverage) . There was no significant difference among the antibiotics in the incidence of immediate or delayed postoperative infections . These data indicate that a less expensive, narrow-spectrum cephalosporin is as effective as more expensive, broader-spectrum cephamycins and cephalosporins as prophylaxis for patients undergoing nonelective cesarean section. J Antibiot (Tokyo), 1991 Sep, 44(9), 940 - 8 Fluvirucins A1, A2, B1, B2, B3, B4 and B5, new antibiotics active against influenza A virus . IV . Taxonomy on the producing organisms; Tomita K et al.; The morphology, chemotaxonomy, and cultural and physiological characteristics were examined on the five strains of actinomycetes which produce antiviral antibiotics, fluvirucin congeners . All strains have meso-2,6-diaminopimelic acid in the cell wall . Four strains, Q464-31, L407-5, R359-5 and R516-16, belong to the maduromycetes since they have madurose in the whole cell . The remaining one strain, R869-90, has rhamnose but no madurose, and is a nocardioform actinomycete . These five strains were classified and designated as follows: Strain Q464-31 (fluvirucin A1 producer): Microtetraspora tyrrhenii sp . nov . (Actinomadura pusilla group) . Strain L407-5 (fluvirucin B2 producer): A maduromycete . Strain R359-5 (fluvirucin B1 producer): Microtetraspora pusilla (Actinomadura pusilla group) . Strain R869-90 (fluvirucin A2 producer): Saccharothrix mutabilis . Strain R516-16 (fluvirucins B2, B3, B4 and B5 producer): A maduromycete. Tijdschr Diergeneeskd, 1991 Sep 1, 116(17), 833 - 40 {How can the incidence of antibiotic residues in meat animals be minimized?}; Nouws JF et al.; The causes of the presence of antibiotic residues in slaughtered animals are analysed . The fact is stressed that the persistence of antibiotic residues in slaughtered animals varies, among other things, with the antibiotic itself, the pharmaceutical design and, in the case of subcutaneous or intramuscular injection, the site of injection and the severity of local irritation of the tissues . There are marked differences between the various antibiotic products as regards the local irritation induced and the residual persistence in organs at the site of injection . A selective use of antibiotics and forms of administration (so-called 'positive list') is advocated, by which the incidence of antibiotic residues in slaughtered animals can be restricted . Recommendations for drawing up a 'positive' list' are made. Toxicol Lett, 1991 Sep, 58(1), 23 - 8 The proconvulsive activity of quinolone antibiotics in an animal model; Williams PD et al.; The side-effect profile of quinolone antibiotics in man includes CNS disturbances such as dizziness, insomnia and convulsions . Although it has been suggested that the proconvulsive liability of quinolones involves an interaction with GABA receptors in the central nervous system, no animal model has been described to evaluate or confirm the mechanism of this effect . The proconvulsive activity of the quinolone antibiotics, nalidixic (NAL) and oxolinic (OXO) acid were tested in male mice following oral doses of 10-100 mg/kg utilizing the convulsive stimuli pentylenetetrazole (PTZ), picrotoxin, strychnine or electroshock . While NAL and OXO did not alter the threshold for convulsions induced by PTZ, strychnine or picrotoxin, both agents lowered the threshold for electroshock-induced seizures . Furthermore, the proconvulsive actions of NAL and OXO were completely blocked by the excitatory amino acid receptor antagonists, MK-801 and 2-amino-4-phosphonobutyric acid (AP-4) . These data indicate that the mechanism of convulsive liability of quinolone antibiotics does not involve GABA receptor interactions as previously thought, but appears to involve activation of excitatory amino acid (EAA) receptors, possibly located in the optic region of the central nervous system. Arkh Anat Gistol Embriol, 1991 Sep-Oct, 101(9-10), 18 - 20 {The functional morphology of the regional inguinal lymph nodes during the endolymphatic antibiotic therapy of patients with vascular diseases of the lower extremities}; Kurkin AV et al.; The general structure and cell composition of the inguinal lymph nodes has been analysed at a direct endolymphatic antibiotic therapy, performed with the aim of prophylaxis of suppurative complications, when surgical interventions are performed in the vessels of the lower extremities . Morphokinetics of the lymph nodes depends on duration of the endolymphatic therapy . During early terms it reflects an increase in transport function of the regional inguinal lymph nodes, during late terms it reflects an increase in their immune role . In the lymph nodes, situating on the contralateral side, an analogous reaction is revealed; this appears to demonstrate presence of well developed collaterals between lymph vessels of the lower extremities. Klin Med (Mosk), 1991 Sep, 69(9), 29 - 31 {Antibiotic therapy of suppurative-inflammatory lesions of the bronchi with endobronchial use of low-frequency ultrasonic energy}; Ovcharenko SI et al.; Gentamycin pharmacokinetics and its concentrations in bronchial secretion were studied in routine endobronchial introduction versus endobronchial aerosol spraying with application of low-frequency ultrasound . The latter technique warranted gentamycin concentrations in bronchial secretion 24 hours after the procedure many times that minimal for inhibition of the pathogen isolated . Secretion levels of gentamycin remained high for 4 days . No side effects were reported . The findings provide evidence in favor of endobronchial aerosol spraying of the drugs for treatment of purulent endobronchitis in bronchiectasis and chronic bronchitis. Infection, 1991 Sep-Oct, 19(5), 301 - 4 Antibiotic usage in community-acquired pneumonia: results of a survey in 288 departments of internal medicine in German hospitals; Kappstein I et al.; In 1989 a survey was conducted in 800 medical departments of university hospitals and large to small teaching and non-teaching hospitals in the Federal Republic of Germany and West Berlin to gather information on the usage of antibiotics for the treatment of community-acquired pneumonia . A total of 288 (36%) questionnaires could be evaluated . In cases of non-life-threatening pneumonia, the therapy specified was mostly correct, although macrolides as the treatment of choice were stated only rarely (11%) . However, patients with life-threatening pneumonia were most often (50%) treated with new beta-lactam antibiotics or beta-lactam antibiotics in combination with aminoglycosides (43%) . Thus, atypical pathogens causing pneumonia were not covered by most therapeutic regimens. J Biomed Eng, 1991 Sep, 13(5), 424 - 8 Effects of fused-ring antibiotics on metallic corrosion; von Fraunhofer JA et al.; The effect on metallic corrosion of antibiotics containing the fused-ring structure of tetracycline (doxycycline and the dihydrate and hydrochloride salts of oxytetracycline) when present in 1% KCl solution was investigated . Corrosion potential and zero resistance ammetry studies were carried out; the effects observed were variable and depended upon the nature of the metal and its surface condition . All three antibiotics appeared to stimulate the corrosion of Vitallium (cobalt-chromium alloy), but corrosion inhibition was found for as-received titanium with all three antibiotics, for abraded titanium with doxycycline and for stainless steel with oxytetracycline dihydrate. Mikrobiol Zh, 1991 Sep-Oct, 53(5), 11 - 5 {The interrelation between the formation of oleandomycin and the resistance to it in different strains of Streptomyces antibioticus}; Shevchenko AA et al.; Strains, producers of oleandomycin, with different level of antibiotic-formation have been studied for their resistance to their own antibiotic . The obtained highly active strain possesses double resistance to oleandomycin and 50% higher activity . Identity of oleandomycin phosphate substances synthesized by initial and produced highly active strains is shown by the HELC method. Antibiot Khimioter, 1991 Sep, 36(9), 19 - 20 {Pharmacokinetics of an antibiotic administered in cell carriers}; Gening TP et al.; Tissue distribution of erythrocyte membrane-bound gentamicin was studied in non-inbred albino rats . Gentamicin was administered to the animals intravenously in single doses of 3.3 mg/kg as a free substance of the antibiotic or in carrier erythrocytes . The gentamicin concentration was determined in serum, blood and tissues of the liver, kidneys, lungs, spleen and the skeletal muscles by fluorescence polarization immunoassay (TDx, Abbott) . Encapsulation of gentamicin in erythrocytes caused changes in its pharmacokinetics: the antibiotic half-life and mean retention time appeared to be higher and the antibiotic accumulation in the liver, spleen and kidneys increased 1.7-3.0, 19-27 and 1.5 times respectively depending on the technique of the carrier erythrocytes preparation . Exposure of the erythrocytes to tannin led to an increase in the rate of the antibiotic release from the carrier erythrocytes. Antibiot Khimioter, 1991 Sep, 36(9), 11 - 3 {Comparative study of fungicidal and herbicidal activities of salts of polyenic macrolide antibiotics}; Belakhov VV et al.; The fungicidal and herbicidal activities of water soluble salts of levorin, nystatin, mycoheptin and amphotericin B, polyenic macrolide antibiotics, were studied . The biological tests showed that the antibiotics had fungicidal and low herbicidal activities . They also had a growth regulating action. Kansenshogaku Zasshi, 1991 Sep, 65(9), 1130 - 5 {Nosocomial infections due to methicillin-resistant S . aureus (MRSA) at the Kagoshima University Hospital (2) . Susceptibility to antibiotics}; Nishi J et al.; Susceptibility to antibiotics of 123 MRSA strains isolated at the Kagoshima University Hospital in 1989 was examined . The results were as follows: 1) Susceptibility of MRSA strains was excellent to VCM, MINO, and RFP, followed by IMP, CLDM, and CPFX . However, most strains were resistant to PCG, MPIPC, ABPC, CET, CMZ, CZON, GM, and AMK . 2) Five strains highly resistant to RFP were isolated . Three of these strains were isolated on the ward for tuberculosis . This suggests easy development of resistance to RFP by MRSA . 3) Differences in susceptibility to antibiotics between coagulase type II and type VII strains were examined . The cumulative percentage of type II strains susceptible to CLDM (MICs less than 0.5 microgram/ml) was 15.3%, and that of type VII was 45.2% . Strains resistant to CLDM were more frequently isolated among type II than among type VII strains (p less than 0.001) . A similar relationship between strains and antibiotics was also found with EM and CPEX . On the other hand, the cumulative percentage of type II strains susceptible to AMK (MICs less than 25 micrograms/ml) was 89.7%, and that of type VII was 9.7% . Strains resistant to AMK were more frequently isolated among type VII than among type II strains (p less than 0.001). Semin Respir Infect, 1991 Sep, 6(3), 158 - 67 Delivery of topical antibiotics: pharmacokinetics and clinical problems; Ilowite JS et al.; Despite major advances in new therapeutic agents to treat pneumonia, pneumonia remains a major cause of morbidity and mortality in hospitalized patients . Topical antibiotics offer many potential advantages in the treatment and prevention of nosocomial pneumonia . These include a high delivery of the drug to the site of infection and the potential for little systemic absorption and, as a result, reduced side effects . The potential disadvantages include failure of topical therapy to reach all diseased areas of the lung and the emergence of resistant organisms . Failure of many of the previous clinical studies has been ascribed to these potential disadvantages . However, little attention has been paid in previous clinical studies to actual dosage and regional distribution of aerosolized antibiotics in the lung and the pharmacokinetics of the aerosol after deposition . One major exception to this has been the use of aerosolized pentamidine, in which careful attention has been paid to nebulizer design, dosage to the lung, regional distribution, and pharmacokinetics . It should serve as the model for the testing of topical antibiotics therapy in the future. MD Comput, 1991 Sep-Oct, 8(5), 282 - 8, 315 The HELP system: a review of clinical applications in infectious diseases and antibiotic use; Evans RS; The HELP hospital information system, now under development for more than 20 years, has become an essential part of the daily operation of LDS Hospital, a 500-bed tertiary-care facility in Salt Lake City, Utah . The overall goal of the system is to provide decision-making capabilities for medical personnel and thus improve patient care . Since 1983, clinical applications have been available to improve the use of antibiotics and increase infection control . This article describes these applications and the essential features of the HELP system. Circ Shock, 1991 Sep, 35(1), 14 - 24 Cardiac output and organ blood flow in experimental septic shock: effect of treatment with antibiotics, corticosteroids, and fluid infusion; Ottosson J et al.; Septic shock from intraperitoneal (i.p.) injection of live Escherichia coli bacteria in rats induces marked pathophysiological changes, including 40% decrease in plasma volume (PV), cardiac output, and oxygen consumption with 100% mortality within 24 hr . The present study evaluates cardiac output and organ blood flow before and after treatment of septic shock with an effective antibiotic (AB), plasma volume (PV) expansion, and corticosteroids (CS), alone and in combination . Treatment was initiated at 5.5 hr after bacterial injection, at a time when AB therapy did not improve 24 hr survival rate . Cardiac output decreased from 28.6 +/- 3.1 (SD) to 15.4 +/- 2.8 ml/min/kg (P less than .01) in septic rats concomitant with redistribution of blood flow from carcass to the heart, brain, intestines, liver, and adrenal glands . Absolute arterial blood flow increased only to the adrenal glands and the liver to 158% (P less than .01) and 167% (P less than .01) of control values, respectively . AB, CS, and Ringer's lactate (RL) alone or in combination did not significantly improve any organ blood flow compared to untreated septic animals but increased survival significantly to about 60% (P less than .01) . Albumin (ALB) and CS in combination expanded PV to 138% (P less than .01), restored cardiac output to 100%, and achieved supranormal blood flow values to the brain (109%), liver (125%), small intestine (147%) (P less than .01), and kidneys (190%) (P less than .01) of preshock levels . More importantly, survival at 24 hr was 90% (9/10) (P less than .001) . It is concluded that a colloid diluted in an electrolyte solution, combined with CS, and an effective antibiotic agent are necessary therapeutic ingredients for the successful recovery of experimental E . coli sepsis. Mol Gen Genet, 1991 Sep, 228(3), 372 - 80 Transcriptional organization and regulation of an antibiotic export complex in the producing Streptomyces culture; Caballero JL et al.; Three open reading frames (ORFs) in the actII region of the actinorhodin biosynthetic gene cluster of Streptomyces coelicolor A3(2), which are involved in the export of the antibiotic are carried on two divergent transcripts . A monocistronic transcript carries actII-ORF1, encoding a putative repressor protein, and a bicistronic transcript codes for actII-ORF2 and -ORF3, whose products have been postulated to form an antibiotic export complex . The actII-ORF1 and actII-ORF2/3 transcripts each have a single promoter and the promoters for the two transcripts overlap . Both promoters are most active in cultures that have developed to the stage of actinorhodin production . The promoters resemble consensus promoters of the vegetative class in Escherichia coli and Streptomyces . We also demonstrate that these promoters are expressed in E . coli and use this finding to reveal a regulatory role for the repressor, using the xylE reporter gene on promoter-probe shuttle vectors and regulated expression of the actII-ORF1 gene under control of Plac . The actII-ORF2/3 promoter is strongly repressed by the ORF1 product and the ORF1 product also represses its own promoter . The finding that the operator/promoter arrangement, and regulatory interconnection, of an antibiotic export/repressor gene pair in Streptomyces strikingly resemble those for tetracycline resistance in bacteria of clinical importance supports the hypothesis of an evolutionary origin of such genes in an ancestral actinomycete. Pharm Weekbl Sci, 1991 Aug 23, 13(4), 179 - 81 Antibiotic concentrations in the groin wound after vascular prosthetic implantation; Van Loenen AC et al.; The kinetics of systemically and locally administered cefuroxime or ceftazidime in wound fluid were investigated in the period after vascular prosthetic implantation . Cefuroxime or ceftazidime was administered intravenously in patients . Simultaneously 250 mg ceftazidime or cefuroxime was added to preclotted blood . Locally administered antibiotics could not be detected in our samples . In groin fluid samples 24-48 h after the operation the average concentration of cefuroxime was 8.3 and of ceftazidime 5.0 mg/l . The decline of the concentration of cefuroxime or ceftazidime in groin fluid seems to be much slower than one would expect from the half-lives of the antibiotics . We conclude that cefuroxime and to a lesser extent ceftazidime are suitable as prophylactic agents in arterial reconstruction. Cell, 1991 Aug 23, 66(4), 769 - 80 The act cluster contains regulatory and antibiotic export genes, direct targets for translational control by the bldA tRNA gene of Streptomyces; Fernandez-Moreno MA et al.; The actII region, flanked by biosynthetic genes in the 25 kb act cluster of S . coelicolor, consists of four open reading frames, including a transcriptional activator for the biosynthetic genes, and genes controlling antibiotic export . A TTA codon (extremely rare in Streptomyces) is present both in actII-ORF2 (encoding a putative transmembrane export protein) and actII-ORF4 (the transcriptional activator gene) . Change of the TTA in ORF4 to TTG reverses the normal interruption of actinorhodin synthesis caused by mutation in the pleiotropic regulatory gene bldA (which encodes the cell's tRNA(Leu)(UUA)) . We conclude that initiation of actinorhodin synthesis via the actII-ORF4 product, and the final step in production, antibiotic export, are twin targets via which bldA exerts developmental control of actinorhodin production. Vet Rec, 1991 Aug 10, 129(6), 109 - 11 Long-acting antibiotic formulations in the treatment of calf pneumonia: a comparative study of tilmicosin and oxytetracycline; Laven R et al.; The treatment of an outbreak of acute pneumonia in 50 four- to eight-month-old Friesian and Friesian cross calves is described . At the first visit (day 0) 16 calves received 20 mg/kg bodyweight of oxytetracycline dihydrate intramuscularly and 15 received 10 mg/kg of the macrolide tilmicosin subcutaneously . The remaining 19 in-contact animals were not considered ill enough to be included in the trial and received 20 mg/kg of oxytetracycline dihydrate . The rectal temperature, demeanour, respiratory rate and respiratory effort of each calf was assessed on days 1, 2, 3, 9, 14, 21 and 28, and calves which had not responded were given repeat injections of the same antibiotic . All the calves recovered from the outbreak and of the 19 calves treated strategically, three required a second injection . Among the calves with clinical pneumonia, fewer treatments (P less than 0.01) were required by those treated with tilmicosin . The rectal temperatures of both groups decreased (P less than 0.05) after the first injection, but on day 3 the decrease was greater (P less than 0.05) in the group treated with tilmicosin . Respiratory rates varied widely but respiratory effort was less (P less than 0.05) on day 2 in the calves treated with tilmicosin . When long-acting antibiotic injections are used to treat enzootic pneumonia it is suggested that a second visit should be made on day 3 to assess the animals' response to treatment. Orthopedics, 1991 Aug, 14(8), 841 - 4 Suppressive antibiotic therapy in chronic prosthetic joint infections; Tsukayama DT et al.; Thirteen patients with chronic total joint infections (eight knees, five hips) were treated with suppressive antibiotic therapy and retention of the prosthesis following surgical debridement and 4 to 6 weeks of intravenous antibiotic therapy . These patients faced poor functional outcome after prosthesis removal . After a mean follow up of 37.6 months (range: 24 to 55), only three patients have retained their prostheses . Ten patients required prosthesis removal for recurrent infection a mean of 21.6 months (range: 6 to 48) after starting suppressive therapy . In addition, 38% of patients experienced adverse effects which led to changes in the antibiotic regimen . Suppressive antibiotic therapy in the treatment of chronic prosthesis infections has limited clinical efficacy and is associated with a substantial risk of adverse effects. Clin Pharmacol Ther, 1991 Aug, 50(2), 215 - 20 Antibiotic use after cefuroxime prophylaxis in hip and knee joint replacement; Wymenga AB et al.; The amount of additional antibiotics measured by defined daily dose (DDD) methods after 2651 hip and 362 knee replacements was assessed after prophylaxis with one or three doses (1502/1511 patients) of cefuroxime . No differences were observed between the two regimens with respect to total amount, type, indication, and duration of additional antibiotics . The incidence of joint sepsis did not differ significantly between the two trial arms, but the sample was too small for definite conclusions . There were 11.4 DDD/100 bed days of additional antibiotics used in 21% of patients after hip replacement and 15.7 DDD/100 bed days in 31% after knee replacement . For wound problems, 3.8 and 6.9 DDD/100 bed days were given in the hip- and knee-replacement groups . For distant infection, 6.5 DDD/100 bed days was administered in both groups . Duration of therapy varied only in relation to indication . Prescribed were penicillins (43% to 50%), sulfonamides (18%), cephalosporins (10% to 16%), and nitrofurantoin (8% to 13%); drug use was related to the type of infection. Am J Dis Child, 1991 Aug, 145(8), 946 - 9 Evaluation of intraosseous vs intravenous antibiotic levels in a porcine model; Jaimovich DG et al.; OBJECTIVES . To compare intraosseous vs intravenous routes of administration and their effects on serum levels of four antibiotics in an animal model . DESIGN . Prospective controlled study comparing two routes of drug administration . SETTING . Research laboratories of a large pharmaceutical company . PARTICIPANTS . Twenty male and female domestic swine weighing 10 to 20 kg . INTERVENTIONS . The animals were anesthetized and treated with controlled ventilation . The animals were divided into one of four groups: (1) intravenous and intraosseous cefotaxime sodium (50 mg/kg), (2) intravenous and intraosseous chloramphenicol sodium succinate (25 mg/kg), (3) intravenous and intraosseous vancomycin hydrochloride (15 mg/kg), or (4) intravenous and intraosseous tobramycin sulfate (2.5 mg/kg) . There was a 24-hour clearance period for groups 1 and 2 and a 48-hour clearance period for groups 3 and 4 . Serum drug levels were measured at 1, 15, 30, 45, 60, 90, and 120 minutes after intravenous and intraosseous administration of the respective antibiotics . Control and treated tibias were sampled for drug levels at the end of the experiment . MEASUREMENTS AND MAIN RESULTS . - Peak serum concentrations for intravenously administered antibiotics were within the therapeutic range . Peak serum levels after intravenous and intraosseous administration were 102 and 82 mg/L, respectively for cefotaxime; 13.9 and 6.3 mg/L, respectively, for chloramphenicol; 24.5 and 3.8 mg/L, respectively, for vancomycin; and 7.1 and 1.3 mg/L, respectively, for tobramycin . CONCLUSIONS . Cefotaxime may be administered intraosseously when intravenous access is not possible . We cannot recommend chloramphenicol or vancomycin for intraosseous administration, because serum levels were not comparable with those following intravenous administration . Findings with tobramycin suggested a lack of achievement of serum levels comparable with those following intravenous administration. J Med Chem, 1991 Aug, 34(8), 2366 - 73 Modeling study of the structure of the macromolecular antitumor antibiotic neocarzinostatin . Origin of the stabilization of the chromophore; Ishiguro M et al.; A three-dimensional structure of the apoprotein of neocarzinostatin (NCS) was built by using the actinoxanthin (AXN) crystal structure as template, and the subsequent favored-site search for the binding of the fragments of the chromophore of NCS at the binding cleft led to a reasonable complex structure of apo-NCS and the chromophore, after refinement of the molecular mechanics program AMBER . The refined three-dimensional structure model of NCS shows the "Y"-shaped cleft of the binding site in which the bicyclic epoxy dienediyne part 4 and its substituents, the naphthoate 3, the amino sugar 2, and cyclic carbonate 1 moieties are nicely fitted . Contacts of the chromophore with the specific amino acid residues in the cleft indicate their contribution to the specific and high affinity binding through ionic interaction, hydrogen bonding, aromatic stacking, and van der Waals contact . Stabilization of the labile chromophore is likely due to the steric hindrance toward the reactive sites such as the C12 position as well as the epoxide, and, more interestingly, the stabilization interaction between the disulfide group (Cys37 and Cys47) and the acetylenic bond is also suggested. ZWR, 1991 Aug, 100(8), 522 - 5 {Antibiotic support with oral penicillin in ambulant therapy for odontogenic infections}; Walz C et al.; In an open clinical trial 51 patients suffering from odontogenous infections were treated with 3 mega units of propicillin (potassium salt) daily for a period of 5 to 10 days . During the therapy all objective and subjective symptoms disappeared or were markedly improved . Only two patients reported slight side effects (gastric disorders, exanthema) . Propicillin proved to be an effective and well tolerated supplement for the surgical therapy of odontogenous infections. J Chemother, 1991 Aug, 3(4), 236 - 9 In vitro and ex vivo effects of recent and new macrolide antibiotics on chemotaxis of human polymorphonuclear leukocytes; Torre D et al.; The effects of five macrolide antibiotics: erythromycin, josamycin, miokamycin, roxithromycin and rokitamycin, on human polymorphonuclear leukocyte (PMN) chemotaxis was studied in vitro and ex vivo . At therapeutic concentrations none of the antibiotics tested affected in vitro PMN chemotaxis . In vitro, erythromycin, josamycin, miokamycin, roxithromycin and rokitamycin decreased PMN chemotaxis significantly only at the concentration of 10 mg/l, which is not usually reached in vivo . Ex vivo studies after the ingestion of therapeutic doses of erythromycin, josamycin, miokamycin and roxithromycin by five volunteers showed a significant effect on PMN chemotaxis . However, further studies are needed to confirm and better evaluate the clinical significance of recent and novel macrolides on PMN chemotaxis. Int J Biol Macromol, 1991 Aug, 13(4), 225 - 30 Degradation of beta-lactam antibiotics in the presence of Zn2+ and 2-amino-2-hydroxymethylpropane-1,3-diol (Tris) . A hypothetical non-enzymic model of beta-lactamases; Company M et al.; The system composed of 2-amino-2-hydroxymethylpropane-1,3-diol (Tris) and Zn2+ catalyses the degradation of cephalosporins . The beta-lactam opening fits to a first-order process, with a constant directly proportional to the zinc ion concentration . The pH and Tris concentration dependency displayed by the first-order constant, as well as the nature of the degradation products point to a mechanism that can be considered as an extension of that proposed for the benzylpenicillin degradation . The mechanism proposed here, and the values of the kinetic constants calculated, as compared with those of beta-lactamases, lead to the conclusion that the Tris-Zn2+ system simulates the catalytic action of the serine beta-lactamases rather than the action of the Zn(2+)-dependent type of enzymes. Rinsho Shinkeigaku, 1991 Aug, 31(8), 837 - 41 {A case of Garcin's syndrome caused by pachymeningitis secondary to otitis media, responsive to antibiotic therapy}; Ishii A et al.; A 55-year-old woman noticed progressive hearing loss, earache and tinnitus in the left side in December 1988, followed by dysesthesia of the left face and hypogeusia . Those symptoms did not respond to the otological treatment of otitis media . In addition, the left eyelid ptosis, double vision and dysphagia appeared in May 1989 . On admission, cranial nerves from III to XII were affected exclusively in the left side . The cell counts and the protein levels in the CSF were elevated . The MRI of the head showed hypertrophic dura mater at the left base of the skull covering the temporal lobe . No bone destruction was found in CT . The biopsy revealed the thickened dura mater with microabscess containing Langhans giant cells and lymphocytes . A diagnosis of pachymeningitis was made . After the therapy with antibiotics and then with prednisolone for several months, cranial nerve disturbances disappeared except hearing loss with decrease in cell counts and protein levels of the CSF . The follow-up MRI after one year showed decrease in thickness of dura mater . The MRI, particularly using enhancement with Gd-DTPA, was useful to make a diagnosis of hypertrophic pachymeningitis . It is suggested that the administration of antibiotics should be considered in the treatment of the pachymeningitis even if the causative agents were not identified. Antibiot Khimioter, 1991 Aug, 36(8), 3 - 6 {Selection of the optimal conditions for the procurement and regeneration of protoplasts of the industrial strain of Streptomyces rimosus, the producer of oxytetracycline, and the effect of the protoplasting process on the antibiotic activity}; Solnyshkina TV et al.; Optimal conditions for protoplasting of the Streptomyces rimosus industrial strain No . 1 producing oxytetracycline were developed . Observation of the early stages of the protoplast regeneration in microchambers showed that there were two regeneration types: normal and anomalous . The latter was likely defined by the glycine effect on cell wall synthesis . It was accompanied by the stage in which the protoplasts had the form of multiplying protoplast-like cells . The protoplasting of the S . rimosus culture producing oxytetracycline resulted in an increase in the variability of an antibiotic producing property and the frequency of low active variants. Indian J Biochem Biophys, 1991 Aug, 28(4), 227 - 32 Polyene antibiotics in the membrane environment; Shervani Z et al.; The cytotoxic activity of the polyene antibiotics mainly depends on the appearance of the drug species which arises from drug-sterol complexation . The unsaturation and intact macrolide ring of the polyenes are the requirements for the biological activity . All the polyene antibiotics can form the complex with the sterol having 3 beta-OH group, and planar ring and a hydrophobic side chain . Aromatic polyene antibiotics with positively charged head group have been considered as most potential antifungal agents. Appl Environ Microbiol, 1991 Aug, 57(8), 2164 - 70 Mechanism of action of the peptide antibiotic nisin in liposomes and cytochrome c oxidase-containing proteoliposomes; Gao FH et al.; The interaction of the peptide antibiotic nisin with liposomes has been studied . The effect of this interaction was analyzed on the membrane potential (inside negative) and the pH gradient (inside alkaline) in liposomes made from Escherichia coli phosphatidylethanolamine and egg phosphatidylcholine (9:1, wt/wt) . The membrane potential and pH gradient were generated by artificial ion gradients or by the oxidation of ascorbate, N,N,N',N'-tetramethyl-p-phenylenediamine, and cytochrome c by the beef heart cytochrome c oxidase incorporated in the liposomal membranes . Nisin dissipated the membrane potential and the pH gradient in both types of liposomes and inhibited oxygen consumption by cytochrome c oxidase in proteoliposomes . The dissipation of the proton motive force in proteoliposomes was only to a minor extent due to a decrease of the oxidase activity by nisin . The results in these model systems show that a membrane potential and/or a pH gradient across the membrane enhances the activity of nisin . Nisin incorporates into the membrane and makes the membrane permeable for ions . As a result, both the membrane potential and pH gradient are dissipated . The activity of nisin was found to be influenced by the phospholipid composition of the liposomal membrane. FEBS Lett, 1991 Jul 8, 285(1), 115 - 9 X-Ray structure of the antibiotic bacitracin A; Pfeffer S et al.; Bacitracins are a group of widely used peptide antibiotics . There has been interest in determining the three-dimensional structure of the bacitracins . However, solution studies indicate significant flexibility in their structure and to date native bacitracins have resisted attempts at crystallisation despite considerable efforts over a number of years by several groups . Here we report the first three-dimensional X-ray structure of a bacitracin, complexed to a subtilisin proteinase . X-Ray diffraction data were collected using synchrotron radiation in combination with the Image Plate Scanner system . The complex structure including two enzymes, two bacitracins, 220 water molecules and two Ca2+ ions was refined by restrained least-squares to a crystallographic R factor ( = sigma {{Fo-Fc}}/sigma {Fo}}) of 16.3% at 2.0 A. S Afr Med J, 1991 Jul 6, 80(1), 7 - 10 A survey of inpatient antibiotic use in a teaching hospital; Till B et al.; To assess the appropriateness of inpatient antibiotic use, a 4-week prospective survey in medical, surgical and gynaecological wards was undertaken at Groote Schuur Hospital . A total of 224 prescriptions comprising 680 antibiotics were analysed . Of all patients in the medical, gynaecology and surgery wards, 27%, 26.5% and 32%, respectively, were prescribed antibiotics . The greatest number of inappropriate prescriptions--54%--were found in the gynaecology ward . Prophylactic antibiotic use was highest in the surgical ward at 41% where a very satisfactory 91% was considered appropriate, whereas 66% of gynaecological prophylaxis was inappropriate . Therapeutic use was highest and more often appropriate in the medical wards . Antibiotics classified as restricted according to the hospital antibiotic policy were generally used appropriately, whereas inappropriate choice, dose, frequency of administration, duration, and unnecessary antibiotic use were encountered in 22-100% of cases with unrestricted antibiotics . Particular problems pinpointed in this survey included excessive dosages of penicillin G and amoxycillin, an irrational protocol for the treatment of pelvic sepsis in gynaecology, and frequent inappropriate selection of erythromycin . The greatest expenditure was on amikacin, the only aminoglycoside allowed according to the existing antibiotic policy. Ann Emerg Med, 1991 Jul, 20(7), 772 - 6 Intraosseous administration of antibiotics: same-dose comparison with intravenous administration in the weanling pig; Pollack CV Jr et al.; STUDY OBJECTIVES: To assess the reliability of the intraosseous route of administration for delivery of a loading dose of broad-spectrum antibiotics in a pediatric animal model . DESIGN: Serum levels achieved within 90 minutes of equivalent intraosseous (IO) and IV bolus dosing of ceftriaxone, cefotaxime, and a combination of ampicillin and gentamicin were compared in the weanling pig . SUBJECTS: Twelve female weanling pigs were studied in the Animal Facilities Laboratory at the University of Mississippi Medical Center . INTERVENTIONS: Through a proximal tibial IO catheter, each anesthetized animal received one of the following: 50 mg/kg ceftriaxone, 50 mg/kg cefotaxime, or 300 mg/kg ampicillin followed immediately by 2.5 mg/kg gentamicin . Venous blood was obtained for antibiotic assay at 15, 30, 45, 60, and 90 minutes after IO injection . The animals were allowed to recover, and, after a one-week washout period, each received the same antibiotic and dose as before through a peripheral IV . Levels were assayed at the same intervals and IO versus IV were compared . MEASUREMENTS AND MAIN RESULTS: Comparable serum levels of all four antibiotics were achieved by the two routes . Gentamicin levels were statistically indistinguishable IO versus IV at all assay intervals . Ampicillin and cefotaxime levels achieved by the two routes were equivalent within one hour of dosing . Serum levels of ceftriaxone after IO administration paralleled those after IV dosing but remained significantly lower at all time intervals . CONCLUSIONS: In the weanling pig model, the IO route was used to deliver serum levels of broad-spectrum antibiotics comparable to those attained after IV administration . The data support the use of standard parenteral doses for IO administration . To overcome potential avid protein binding of ceftriaxone in the bone marrow, we recommend using ceftriaxone at its highest recommended IO loading dose . Consistent with many other medications that have been similarly tested, these data indicate that initial or empiric antibiotic coverage in hypodynamic and shock states in infants and young children need not await the establishment of traditional IV access. Antibiot Khimioter, 1991 Jul, 36(7), 10 - 4 {A potentiometric rapid method of determining the level of phenylacetic acid during the production of beta-lactam antibiotics}; Pisarev SV et al.; A potentiometric rapid method for control of phenylacetic acid (PAA) concentration in production of ++beta-lactam antibiotics is described . The method is based on ion selective electrodes with a film membrane . The results of the theoretical and experimental studies on estimation of the electrode selectivity specific of PAA in the presence of various interfering ions are presented . It was shown possible to use the electrodes for PAA control in the media containing nitrates, bicarbonates and chlorides . Recommendations how to use the ion selective electrodes at various stages in production of ++beta-lactam antibiotics are given . Prospects for improving the method and designing an instrument for rapid assay of phenyl acetate ion activity are discussed. Vestn Oftalmol, 1991 Jul-Aug, 107(4), 56 - 9 {Antibiotic levels in the lacrimal fluid and liquid ocular media in various routes of drug administration}; Somov EE et al.; Rabbit experiments (n = 273) and examinations of the lacrimal fluid and aqueous humor of the eye, carried out in 165 patients after antibiotic administration via various routes, have revealed that antibiotics (gentamycin, ampicillin, benzylpenicillin) do not penetrate into the liquid media of the eye or lacrimal fluid after intramuscular injections . These drugs appear in these fluids only after subconjunctival injections; the therapeutic concentration in the lacrimal fluid persists for an hour, that in the anterior chamber fluid for 30-45 min. Ann Ophthalmol, 1991 Jul, 23(7), 263 - 6 Preoperative antibiotic and povidone-iodine preparation of the eye; Grimes SR et al.; We compared gentamicin 0.3% one drop every three hours the night before and the morning of surgery ("half-day regimen") with the same drug one drop qid for three days ("three-day regimen") in 15 eyes undergoing intraocular surgery . Conjunctival cultures of both groups taken before povidone-iodine preparation showed mean colony counts of 3.67 +/- 0.82 in the half-day regimen versus 1.0 +/- 0.43 in the three-day regimen . Conjunctival cultures taken after the administration of a povidone-iodine 5% preparation showed 7.17 +/- 3.52 and 2.75 +/- 0.88, respectively, in the two groups . Although there was a statistical difference in colony counts, topical gentamicin 0.3% given the night before and day of surgery had comparable low colony counts with the three-day course . The 5% povidone-iodine solution was not effective in reducing bacterial flora although it did eliminate all fungal colonies. Diabete Metab, 1991 Jul-Aug, 17(4), 417 - 20 {Does glycemic level influence the pharmacokinetics of an antibiotic (cefoperazone)?}; Gin H et al.; Hyperglycemia may modify pharmacokinetics of some antibiotics as shown in the literature . We studied the influence of glycaemic levels on pharmacokinetics properties of cefoperazone in 12 type 1 insulin dependent diabetic patients . Hyperglycaemia was obtained by a reduction of one quarter of their usual insulin dosage and normoglycaemia by an artificial pancreas (Biostator GCIIS) . Cefoperazone had a high protein affinity and a high biliary elimination . Pharmacokinetic study was performed during a 8 hour period following one gram intravenous bolus . We did not found any influence of glycaemic level (normoglycaemia or hyperglycaemia) on the pharmacokinetic parameters of cefoperazone. Br Poult Sci, 1991 Jul, 32(3), 535 - 44 The effects of dietary concentrations of minerals, source of protein, amino acids and antibiotics on the growth of and digestibility of amino acids by broiler chickens; Shafey TM et al.; 1 . The effects of dietary calcium, available phosphorus, amino acid and antibiotic supplements on the digestibilities of amino acids and growth of broiler chickens were investigated in two experiments . 2 . The performance of chickens fed on diets containing high concentrations of calcium and available phosphorus was poorer with meat meal-based diets than with soyabean-based diets . Methionine supplementation improved the performance of chickens fed meat meal-based diets . 3 . A high dietary content of calcium (25.9 vs 11.8 g/kg) reduced chick performance and the digestibility of glutamic acid, leucine and phenylalanine but increased the digestibility of lysine and histidine . 4 . High dietary contents of calcium and available phosphorus (24.3 and 13.0 vs 11.8 and 4.0 g/kg) reduced chick performance and the digestibilities of most amino acids . 5 . Antibiotic supplementation did not improve the performance of chickens, but increased the digestibilities of most amino acids in chickens fed on diets with a high calcium or high calcium and available phosphorus contents . 6 . It was concluded that excess dietary calcium alone, or calcium and phosphorus together, reduced chick performance and the digestibilities of most amino acids . Growing chickens tolerated excess dietary calcium and available phosphorus better in well-balanced amino acid diets, such as soyabean meal or methionine-supplemented meat meal diets, than in poorly balanced amino acid diets, such as unsupplemented meat meal diets. J Dairy Sci, 1991 Jul, 74(7), 2128 - 37 Antibiotic residue prevention methods, farm management, and occurrence of antibiotic residues in milk; McEwen SA et al.; The objective of this study was to determine associations among the occurrence of antibiotic residues in bulk milk and various farm management practices . Ninety-four dairy farms were visited after antibiotic residues were detected in samples of their bulk milk (case farms) along with an equal number of residue-free farms (controls) . Farmers completed questionnaires designed to elicit details of management practices used on farms and methods employed for prevention of antibiotic residues . Factors were initially examined unconditionally for statistical association with occurrence of residues; then multivariate associations were determined using multiple logistic regression . After adjusting for herd size in a logistic model, the risk of residues in milk was observed to increase in association with the frequent use of part-time labor in the milking of cows . The risk of residue occurrence was decreased in association with the use of milk residue test kits, when the farmer believed that increasing the dose of antibiotic required an increase in the withholding time of milk, and when tie stall and pipeline milking systems were used rather than milking parlors or tie stall and dumping station systems. Food Chem Toxicol, 1991 Jul, 29(7), 477 - 83 Risk assessment of antibiotic residues of beta-lactams and macrolides in food products with regard to their immuno-allergic potential; Dewdney JM et al.; In human medicine drug allergy is a well-established side-effect of the therapeutic use of antibiotics, especially the beta-lactams . Side-effects caused by macrolides are uncommon and only a very few of these seem to be caused by allergic mechanisms . Clinically, drug allergy is characterized by a spectrum of reactions ranging from mild skin rashes to angio-oedema or life-threatening anaphylaxis . Concern has been expressed that antibiotic residues in meat and other foods might be responsible for similar hypersensitivity reactions in a small number of individuals . This review assesses the potential risk of such reactions in general, but focuses on allergy to penicillin and macrolide residues in particular . In relation to the risk of primary sensitization, it is unlikely that residues could contribute to the overall immune response in view of the very low levels that are likely to be encountered in comparison with the high levels received during therapeutic use . No evidence has been found that any individual has become sensitized by residues of either penicillins or macrolides . Furthermore, the oral route is much less sensitizing than parenteral administration and immunochemical studies with penicillin indicate that hapten-protein complexes formed in vivo are unlikely to be immunogenic because of their low dose, low epitope density and binding to autologous carrier proteins . For performed allergens, the epitope density was also too low to be immunogenic . Because of the ubiquitous nature of penicillin-producing moulds in nature and the extensive use of beta-lactam antibiotics in human medicine, it is unlikely that epidemiological studies could be undertaken that could allow quantification of the minimal risk . The risk of allergic reactions in pre-sensitized individuals can be assessed similarly and again it is concluded that factors such as dose, oral administration and low epitope density make it unlikely that a significantly antigenic derivative could be formed . However, a review of the literature on penicillin hypersensitivity revealed a very small number of previously sensitized individuals from whom there is reasonable clinical and documentary evidence that penicillin residues in milk triggered an allergic reaction, usually a rash . Although these cases are very rare (less than 10 cases reported in the last 25 years), they illustrate the continuing need to control antibiotic residues vigilantly . Animal models have not proved useful for predicting the risk of hypersensitivity reactions to drugs, since allergy in man is determined by genetic and other factors and no validated methods exist to determine a no-effect level.(ABSTRACT TRUNCATED AT 400 WORDS) J Antibiot (Tokyo), 1991 Jul, 44(7), 756 - 61 Fluvirucins A1, A2, B1, B2, B3, B4 and B5, new antibiotics active against influenza A virus . III . The stereochemistry and absolute configuration of fluvirucin A1; Naruse N et al.; Fluvirucin A1 was established as (2R,3S,6R, 10S)-3-{(3-amino-3,6-dideoxy-alpha-L-talopyranosyl)-oxy}-2,6-dimethyl-10 -ethyl-13-tridecanelactam by chemical, spectroscopic, and X-ray crystallographic analyses. J Antibiot (Tokyo), 1991 Jul, 44(7), 733 - 40 Fluvirucins A1, A2, B1, B2, B3, B4 and B5, new antibiotics active against influenza A virus . I . Production, isolation, chemical properties and biological activities; Naruse N et al.; Five unidentified actinomycete strains produced a series of novel antiviral antibiotics which have a unique 2,6-dialkyl-10-ethyl-3(or 9)-hydroxy-13-tridecanelactam nucleus substituted with 3-amino-3,6-dideoxy-L-talose or 3-amino-3,6-dideoxy-L-mannose(L-mycosamine) . The antibiotic components exhibited potent inhibitory activity against influenza virus type A Victoria strain infection in Madin Darby canine kidney cells by the cytopathic effect reduction assay. Compendium . 1991 Jul;12(7):492, 494, 496 passim. Prophylactic antibiotics revisited; Bahn SL; This article discusses the more practical and safer oral prophylactic antibiotic regimens recently approved by the American Heart Association and the American Dental Association . The new guidelines are strongly supported by the scientific data combined with an appreciation of the substantial logistic and financial barriers to parenteral prophylactic antibiotic administration to dental outpatients. Farmakol Toksikol, 1991 Jul-Aug, 54(4), 45 - 8 {The effect of antibiotics on the function of type-II and -III glucocorticoid receptors}; Golikov PP; The effects of antibiotics on functioning glucocorticoid receptors of types II and III of male Wistar rat liver cytosol were studied . All the studied antibiotics at the concentration of 10(-3) M increased 1.6-2.4 times the function of glucocorticoid receptors of type III . At the concentration of 10(-4) M, except cephazolin and kanamycin, all antibiotics also enhanced the function of glucocorticoid receptors of types III, although to a lesser degree than at the concentration of 10(-3) M . The influence of antibiotics on the function of glucocorticoid receptors of type II is diverse . If antibiotics of penicillin and cephalosporin group increased, antibiotics of streptomycin, rifamycin, aminoglycosides and levomicetine group, on the contrary, decreased the function of type II glucocorticoid receptors . The practical importance of the agents regulating the function of glucocorticoid receptors is discussed. Steroids, 1991 Jul, 56(7), 354 - 60 Genealogy of regulation of human sex and adrenal function, prostaglandin action, snapdragon and petunia flower colors, antibiotics, and nitrogen fixation: functional diversity from two ancestral dehydrogenases; Baker ME; Metabolism of steroid hormones by dehydrogenases is an important mechanism for regulating steroid hormone action . Analysis of recently reported amino acid sequences of 11 beta-hydroxysteroid dehydrogenase, 17 beta-hydroxysteroid dehydrogenase, and 3 alpha, 20 beta-hydroxysteroid dehydrogenase reveals that they are descended from a common ancestor . Unexpectedly, this superfamily of dehydrogenases has other interesting relatives: 15-hydroxyprostaglandin dehydrogenase, proteins found in nitrogen-fixing bacteria, and enzymes important in the synthesis of antibiotics . The novel lineage of these proteins and the actions of flavonoids in regulating gene transcription in nitrogen-fixing bacteria and mammals provide new insights into the evolution of regulation of gene transcription by intercellular signals in multicellular animals. Mikrobiyol Bul, 1991 Jul, 25(3), 265 - 71 {The effect of some antibiotics on primary antibody response}; Atabey N et al.; In this study, effect of four broad spectrum antibiotics (sodium cefoperazone, sulbactam-ampicillin, mezlocillin, rifamycin) on primary antibody response . Therefore, sheep red blood cells were injected into total 25 rabbits in control and experiment groups . Hemolysin levels were titrated in serum specimens prepared from blood specimens taken before the experiment and taken three weeks after the last antigen injection . It was found that statistically significant in all the experiment groups rather than control (p less than 0.05). Biochimie, 1991 Jul-Aug, 73(7-8), 1145 - 9 Binding sites of the antibiotics pactamycin and celesticetin on ribosomal RNAs; Egebjerg J et al.; The binding sites of the antibiotics pactamycin and celesticetin on the rRNAs of Escherichia coli ribosomes were investigated by a chemical footprinting procedure . Pactamycin protected residues G-693 and C-795 in 16S RNA which are located in an important functional region of the 30S subunit participating in initiation complex formation and ribosomal subunit interaction . Celesticetin altered the reactivities of 5 residues A-2058, A-2059, A-2062, A-2451 and G-2505 within the central loop of domain V of 23S RNA which has been implicated in peptidyltransferase activity . Inferences are drawn concerning the mode of action of the antibiotics. Int J Parasitol, 1991 Jul, 21(4), 403 - 7 An antibiotic-free medium for the xenic cultivation of Entamoeba gingivalis; Gannon JT et al.; Diamond's TYI-S-33 (Trypticase-Yeast Extract-Iron-Serum) medium was used as the basis for a new antibiotic-free medium for xenic growth of Entamoeba gingivalis . Nutritional requirements of the oral protozoan were determined in an effort to optimize growth . TYI-S-33 medium did not support E . gingivalis growth prior to modification . The changes included: (a) deletion of L-cysteine.HCl and thioctic acid, (b) substitution of glucose for dextran I (mol . wt 185,000) or rice starch, (c) reduction of concentrations of tryptone (2.5 g l-1), yeast extract (1.25 g l-1) and dextran I (1 g l-1), (d) increased concentration of ferric ammonium citrate (0.2 g l-1), and (e) addition of gastric mucin (2.4 g l-1) . Dextran I was chosen as the major carbon source; its use in the medium limited growth of accompanying bacteria . This new antibiotic-free medium significantly increased E . gingivalis growth (16-20 E . gingivalis trophozoites observed per field) as compared to growth in Diamond's TYSGM-9 (Trypticase-Yeast Extract-Serum-Gastric Mucin) medium (six to 10 E . gingivalis trophozoites observed per field). Vestn Khir Im I I Grek . 1991 Jul-Aug;147(7-8):64. {The interstitial electrophoresis of antibiotics in treating peritonitis in children}; Topuzov VS et al.; The method was successfully used in 32 children with diffuse and general peritonitis and it may be recommended for clinical practice . No complications resulting from using the method of interstitial electrophoresis were noted. J Chromatogr, 1991 Jun 28, 547(1-2), 411 - 8 Separation and determination of polyether carboxylic antibiotics from Streptomyces hygroscopicus NRRL B 1865 by thin-layer chromatography with flame ionization detection; Auboiron S et al.; Thin-layer chromatography coupled with flame ionization detection was used to develop a method to separate and to determine simultaneously three polyether carboxylic ionophore antibiotics (abierixin, nigericin and grisorixin) produced by Streptomyces hygroscopicus NRRL B 1865 . Various proportions of chloroform, methanol and formic acid (or acetic acid as a substitute for formic acid) were used in the developing solvent to determine changes in RF values of the antibiotics and to allow conditions for maximum resolution to be obtained . Development on Chromarods SII with chloroform-methanol-formic acid (97:4:0.6, v/v/v) gave satisfactory and reliable separations of the three polyether antibiotics . Under these conditions, the internal standard methyl desoxycholate was found to be suitable for their simultaneous determination in the lipid extracts of Streptomyces hygroscopicus NRRL B 1865. Biochem Biophys Res Commun, 1991 Jun 14, 177(2), 688 - 95 Complementary DNA sequence of human neutrophil azurocidin, an antibiotic with extensive homology to serine proteases; Almeida RP et al.; Human neutrophils contain in their azurophil granules four antibiotic proteins with extensive homology to serine proteases, collectively termed serprocidins . Azurocidin is the only member of the group that lacks proteolytic activity . Using a monospecific antibody, we isolated from human bone marrow a cDNA encoding the complete azurocidin protein in its mature form, along with an N-terminal 24 residue hydrophobic peptide . The N-terminal third of the mature protein sequence contains a cluster of positively charged amino acid residues, many of which are predicted to be surface exposed . The primary sequence is highly homologous to elastase, proteinase 3, cathepsin G, T-cell granzymes and other serine proteases . However, azurocidin has Gly for Ser and Ser for His substitutions in the catalytic triad . Southern blot analysis of human genomic DNA suggests the existence of a single azurocidin coding sequence. Nucleic Acids Res, 1991 Jun 11, 19(11), 2897 - 906 Anthracycline antibiotic arugomycin binds in both grooves of the DNA helix simultaneously: an NMR and molecular modelling study; Searle MS et al.; Perturbations to the 1H and 31P chemical shifts of DNA resonances together with twenty-four intermolecular nuclear Overhauser effects show that the anthracycline antibiotic arugomycin intercalates between the basepairs of the hexamer duplex d(5'-GCATGC)2 at the 5'-CpA and 5'-TpG binding sites . In the complex two drug molecules are bound per duplex with full retention of the dyad symmetry . Arugomycin adopts a threaded binding orientation with chains of sugars positioned in both the major and minor groove of the helix simultaneously . The complex is stabilized by hydrogen bonding, electrostatic and van der Waals interactions principally in the major groove and involving substituents on the rigidly oriented bicycloamino-glucose sugar of the antibiotic . A specific hydrogen bond is identified between the C2'-hydroxyl and the guanine N7 at the intercalation site . Together, interactions in the major groove appear to account for the intercalation specificity of arugomycin that requires both a guanine and thymine at the intercalation site . We are unable to identify any sequence specific interactions between the minor groove and the arugarose sugar (S1) which binds only weakly, through van der Walls contacts, over the d(GCA).d(TGC) trinucleotide sequence . The data indicate that the sugar chains of arugomycin are flexible and play little part in the interaction of the antibiotic with DNA . The intensity of sequential internucleotide NOEs identifies the intercalation site as being assymmetric . A family of conformers computed using restrained energy minimisation and molecular dynamics indicate that basepair buckling is a feature of the anthracycline intercalation site that may serve to maximise intermolecular van der Waals interactions by wrapping the basepairs around the antibiotic chromophore. J Theor Biol, 1991 Jun 7, 150(3), 277 - 86 Interaction energy studies on antibiotics nucleoside analogs 2-azaadenine; Sanyal NK et al.; The 2-azaadenine antibiotic is known to be a potent cytotoxic nucleoside analog . Evaluation of the interaction energy of this molecule with nucleic acid bases and base pairs has been performed using a quantum-mechanical perturbation technique . Both in-plane and stacking energies have been computed . These energy values along with their sites of association have been compared with the standard energy values and spatial positions for the nucleic acid bases during transcription . The results have been examined in the light of their biological significance. Cancer Commun, 1991 Jun, 3(6), 173 - 80 DNA damage and cytotoxicity induced by metabolites of anthracycline antibiotics, doxorubicin and idarubicin; Ferrazzi E et al.; This study assessed the ability of major metabolites of two types of anthracycline antibiotics, doxorubicin and idarubicin (4-demethoxydaunorubicin) to damage DNA in mouse fibrosarcoma 935.1 cells . Since DNA lesions by anthracyclines may be mediated by topoisomerase II, we also characterized the ability of the drugs to inhibit this enzyme . The C-13 alcohol and aglycone metabolites of doxorubicin and idarubicin were compared to the parent drugs in terms of induction of DNA single strand breaks measured by filter elution . In whole cells, the maximal DNA strand breakage induced by the C-13 alcohol metabolites was similar to that of their respective parent drugs . In isolated nuclei, however, the alcohol metabolites were two times more potent than the parent drugs . The aglycone metabolites produced very little damage in either whole cells or nuclei . The doxorubicin compounds differed markedly from idarubicin drugs in the way their ability to induce DNA breaks was related to cytotoxic activity . Doxorubicin and doxorubicinol cytotoxic effects (50% cell growth inhibition at 0.2 and 4 microM, respectively) coincided (in terms of drug concentrations) with the induction of significant breakage of cellular DNA . In contrast, the concentrations of idarubicin and idarubicinol needed to produce 50% growth inhibition (0.005 and 0.006 microM, respectively) were about 20 times lower than drug levels that induced significant DNA damage . All six compounds inhibited the catalytic activity of isolated topoisomerase II . While the alcohol metabolites produced this inhibition at concentrations similar to those of their parent drugs (5-10 microM), the aglycones were again much less active.(ABSTRACT TRUNCATED AT 250 WORDS) Mutat Res, 1991 Jun, 260(2), 215 - 8 Inhibitory effect of rat immunization with tularemia vaccine on the in vivo clastogenicity of 4 anthracycline antibiotics; Nersessian AK et al.; We studied the in vivo effect of rat immunization with tularemia live vaccine (TLV) on chromosomal aberrations (CA) induced in bone marrow cells by 4 anthracycline antibiotics . CA induced by adriamycin (ADR) and 4'-epiadriamycin (EADR) in rat bone marrow cells consisted mainly of chromatid breaks (approximately 90%), whereas lesions induced by aclacur (AC) and aclarubicin (ACR) consisted only of chromatid breaks . Preliminary cutaneous immunization of rats with TLV revealed significant suppression of CA induced by all 4 antibiotics . The present and previous results suggest that TLV may be a potent anticlastogenic factor. J Bacteriol, 1991 Jun, 173(11), 3425 - 31 Analysis of murein and murein precursors during antibiotic-induced lysis of Escherichia coli; Kohlrausch U et al.; Lysis of Escherichia coli induced by either D-cycloserine, moenomycin, or penicillin G was monitored by studying murein metabolism . The levels of the soluble murein precursor UDP-N-acetylmuramyl-L-alanyl-D-glutamyl-m-diaminopimelyl-D-alanyl- D-alanine (UDP-MurNAc-pentapeptide) and the carrier-linked MurNAc-(pentapeptide)-pyrophosphoryl-undecaprenol as well as N-acetylglucosamine-beta-1,4-MurNAc-(pentapeptide)-pyrophosphoryl- undecaprenol varied in a specific way . In the presence of penicillin, which is known to interfere with the cross-linking of murein, the concentration of the lipid-linked precursors unexpectedly decreased before the onset of lysis, although the level of UDP-MurNAc-pentapeptide remained normal . In the case of moenomycin, which specifically blocks the formation of the murein polysaccharide strands, the lipid-linked precursors as well as UDP-MurNAc-pentapeptide accumulated as was expected . D-Cycloserine, which inhibits the biosynthesis of UDP-MurNAc-pentapeptide, consequently caused a decrease in all three precursors . The muropeptide composition of the murein showed general changes such as an increase in the unusual DL-cross bridge between two neighboring meso-diaminopimelic acid residues and, as a result of uncontrolled DL- and DD-carboxypeptidase activity, an increase in tripeptidyl and a decrease in tetrapeptidyl and pentapeptidyl moieties . The average length of the glycan strands decreased . When the glycan strands were fractionated according to length, a dramatic increase in the amount of single disaccharide units was observed not only in the presence of penicillin but also in the presence of moenomycin . This result is explained by the action of an exo-muramidase, such as the lytic transglycosylases present in E . coli . It is proposed that antibiotic-induced bacteriolysis is the result of a zipperlike splitting of the murein net by exo-muramidases locally restricted to the equatorial zone of the cell. Geriatrics, 1991 Jun, 46(6), 47 - 54 An update on home intravenous antibiotic therapy; Bernstein LH; Home intravenous antibiotic therapy (HIVAT) has proven to be a safe, effective, and cost-saving method to treat appropriately selected patients with bone, soft tissue, respiratory, genitourinary, and cardiac infections . Further, the acceptance of HIVAT by both physicians and patients has been enhanced by the availability of new venous access devices and home IV therapy companies . In determining when to use HIVAT, it is important to carefully consider the individual patient, the disease or medical condition, and antibiotic selection . HIVAT requires a team approach, with the physician, pharmacist, IV therapy nurse, and others playing critical roles in successful treatment plans. J Antimicrob Chemother, 1991 Jun, 27(6), 741 - 8 Ionic binding, adaptive resistance and post-antibiotic effect of netilmicin and ciprofloxacin; Gould IM et al.; Ionic binding, post-antibiotic effect (PAE) and adaptive resistance to netilmicin and ciprofloxacin were investigated in 11 distinct clinical isolates . Both netilmicin and ciprofloxacin showed concentration dependent kill and PAE when bacteria were exposed to these antibiotics at 37 degrees C . The effects of netilmicin were maintained at 4 degrees C, when there is no energy dependent cell uptake of antibiotic, but were partially inhibited by exposure to NaCl and EDTA although not by Ca++ . This supports the concept that ionic binding to the bacterial cell wall is important in the initial uptake of netilmicin . Ciprofloxacin showed no such effects at 4 degrees C . Adaptive resistance (reduced bacterial kill on second exposure) occurred with both netilmicin and ciprofloxacin but was seen more frequently with netilmicin . It persisted longer than classical PAE but, even after continuous exposure, was not enough to suggest a loss of kill with a twice daily dosing regimen of netilmicin or ciprofloxacin. Int J Epidemiol, 1991 Jun, 20(2), 558 - 64 Experimental evaluation of the effects of drug information on antibiotic prescribing: a study in outpatient care in an area of Sri lanka; Angunawela II et al.; The intervention level of epidemiology is useful for studying effects in health systems research . Due to practical and ethical reasons, it is often difficult to apply experimental methods such as classical randomized clinical trials in the field . However with alternative approaches such as 'randomization by group' some of these problems can be overcome . Drug information has since long been considered as an instrument to influence physicians, however evaluation of its effects is a new field of research . In the present study the impact of drug information on prescribing behaviour was evaluated in an outpatient setting in Sri Lanka . The study included 15 state health institutions (45 prescribers) with a common drug formulary . Groups of prescribers were randomized into two interventions; newsletters and newsletters reinforced by a group seminar, and one control group . The target topic was 'rational prescribing of antibiotics' . Some 18,766 randomly selected outpatient drug prescriptions were studied . Antibiotics (and sulphonamides) were prescribed to 33.2% of the patients . An overall trend towards a decrease in proportion of patients prescribed antibiotics in the two intervention groups was seen, although the difference was not significant (p greater than 0.05) compared to the control group . This is similar to the effect of written information on prescribing in other studies . A mean difference of -7.4% in written, -7.3% in written + seminar and -0.4% in the control group was shown . The general antibiotic prescribing pattern did not change in any of the three groups . Penicillin was the most commonly prescribed antibiotic and tetracycline was only rarely prescribed to children . This experiment indicates the feasibility of drug information intervention studies in developing countries.(ABSTRACT TRUNCATED AT 250 WORDS) DICP, 1991 Jun, 25(6), 662 - 7 Use of restricted antibiotics in primary care; Zara C et al.; The objective of this study was to detect and evaluate the use of restricted antibiotics (RAs) in our ambulatory care site . We retrospectively analyzed 1084 treatments of a selected group of intramuscularly administered antibiotics that are usually considered restricted for use in hospitals . Five cephalosporins, four aminoglycosides, and one acylureidopenicillin were analyzed . The study was conducted in 47 primary health centers over six months . We reported the information on a special order form for parenteral prescriptions and evaluated the selection and the dosing interval of each antibiotic . Of the 1084 treatments, cefonicid was the antibiotic most frequently prescribed (61.3 percent), followed by tobramycin (15.3 percent), cefotaxime sodium (6.7 percent), amikacin (3.8 percent), cefuroxime (3.8 percent), mezlocillin (3.7 percent), netilmicin sulfate (3.7 percent), ceftizoxime sodium (0.8 percent), cefoxitin (0.5 percent), and streptomycin sulfate (0.4 percent) . Based on our survey criteria, 59 percent of the 710 orders that indicated diagnosis had a correct or possibly correct indication; the remaining percentage was considered unnecessary therapy or poor drug choice . Of the 1050 orders that indicated a dosing interval, 75.4 percent showed an appropriate dosing interval . We assume that most of the infections treated in our ambulatory care site could be resolved with or without common antibiotics . In this study we obtained objective data of the use of ten RAs in order to determine if their use in ambulatory patients was justified . We observed that a small number of prescriptions agreed with the recommended criteria stated in this survey for use of these antibiotics in outpatient infections. Clin Obstet Gynecol, 1991 Jun, 34(2), 345 - 51 Intrapartum antibiotic therapy for suspected intraamniotic infection: impact on the fetus and neonate; Maberry MC et al.; Acute chorioamnionitis occurs relatively frequently in pregnancy and may result in significant fetal and neonatal morbidity . Although there is no unanimity of opinion regarding the most efficacious antibiotic regimen for the treatment of this complication, there is a consensus, at least among obstetricians, that maternal treatment may have an impact on neonatal outcome . It appears that the fetus and neonate benefit from "intrauterine" treatment . Virtually all antibiotics cross the placenta, and fortunately most are relatively safe for use during pregnancy. Microbiologia, 1991 Jun, 7(1), 1 - 12 Genes directly involved in the biosynthesis of beta-lactam antibiotics; Barredo JL et al.; Several genes encoding enzymatic activities involved in penicillin and cephalosporin biosynthesis have been identified . The first two steps in the biosynthesis of both antibiotics are common in penicillin, cephalosporin and cephamycin producers: condensation of the three precursor amino acids to form the tripeptide delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine, and oxidative cyclization of the tripeptide to form isopenicillin N . The genes involved in the two steps are pcbAB and pcbC respectively . The conversion of isopenicillin N to penicillin G is carried out by the enzyme isopenicillin N:6-APA acyltransferase encoded by the gene penDE . The biosynthesis of cephalosporin diverges from that of penicillin G at the isopenicillin N level . The isopenicillin N is first isomerized to penicillin N by an epimerase that is encoded by the gene cefD . The penicillin N is converted in deacetoxycephalosporin C by an expansion of the five-membered thiazolidine ring to the six-membered dihydrothiazine ring . The deacetoxycephalosporin C is finally converted into cephalosporin C by a hydroxylation and O-acetylation . The enzymes which catalyze these last three steps are encoded by the genes cefE, cefF and cefG . The penicillin, cephalosporin and cephamycin biosynthetic genes are organized in clusters (and subclusters) of genes. Wei Sheng Wu Xue Bao, 1991 Jun, 31(3), 247 - 50 {Studies on the antitumor antibiotic aclacinomycin A}; Zhang H et al.; During the course of screening for new antitumor antibiotics, a new anthracycline antibiotic--aclacinomycin A was separated from the broth and mycelium of Streptomyces AC-57 . The strain AC-57 was isolated from the soil collected in the Shanghai suburbs . According to its culture and physiological characteristics the producer was identified as Str . galilaeus AC-57 . The broth and mycelium were extracted and treated with solvents as usual way . The aclacinomycin A was separated by silica-gel column chromatography eluted with chrolo-form-methanol . Aclacinomycin A, its aglycone and sugar components were identified by comparison of their physico-chemical and spectral data (MS, UV, IR, 1H-NMR, and 13C-NMR) with authentic compound, purified from the market sample. Clin Chest Med, 1991 Jun, 12(2), 395 - 407 Oral antibiotics for pneumonia; Hampson NB et al.; The majority of patients presenting with community-acquired pneumonia can be treated with oral antibiotics and can be managed successfully as outpatients . Oral-antibiotic selection requires a knowledge of the classes of antibiotics available, utility of diagnostic testing, epidemiology of pneumonia, and a rational approach to empiric therapy when a cause cannot be immediately identified . These topics are reviewed, with the goal improved therapeutic efficacy in the oral treatment of pneumonia. Pharm Res, 1991 Jun, 8(6), 706 - 12 A polymer carrier system for taste masking of macrolide antibiotics; Lu MY et al.; A polymer carrier system was developed to reduce the bitterness of erythromycin and its 6-O-methyl derivative, clarithromycin, by absorption to Carbopol . The mechanism involves ionic bonding of the amine macrolide to the high molecular weight polyacrylic acid, thereby removing the drug from the solution phase in an ion-free suspension . After ingestion, endogenous cations displace the drug from the polymer in the gastrointestinal tract to achieve bioavailability . The macrolide-Carbopol complexes were prepared by dissolving or slurrying predetermined ratios of drug and polymer in water or hydroalcoholic mixtures . A series of in vitro equilibrium studies, taste screening, and bioavailability studies in dogs established the characteristics for the various drug-polymer ratios . Taste protection was further improved by encapsulating the adsorbate particles with polymer coatings . Hydroxypropyl methylcellulose phthalate (HP-55) provided the best combination of suspension stability, taste protection and bioavailability . Human bioavailability studies demonstrated that the microencapsulated Carbopol absorbates of erythromycin and clarithromycin gave blood levels comparable to those obtained from conventional solid formulations. Antimicrob Agents Chemother, 1991 Jun, 35(6), 1186 - 90 Comparison of the effects of the new azalide antibiotic, azithromycin, and erythromycin estolate on rat liver cytochrome P-450; Amacher DE et al.; Erythromycin and some other macrolide antibiotics can first induce a cytochrome P-450 isozyme similar to the one induced in rats by pregnenolone-16 alpha-carbonitrile and then inhibit it by forming a stable cytochrome P-450-metabolite complex . The purpose of this study was to compare azithromycin, a novel 15-membered ring azalide, and erythromycin estolate for the potential to cause hepatic microsomal enzyme induction and inhibition in Sprague-Dawley rats . The daily oral administration of 800 mg of erythromycin estolate per kg for 7 days resulted in statistically significant elevations of NADPH-cytochrome c reductase, erythromycin N-demethylase (3.2-fold), and total cytochrome P-450 content . Approximately 40% of cytochrome P-450 was complexed with erythromycin metabolite . In contrast, the daily administration of 200 mg of azithromycin per kg for 7 days caused significant elevations of N-demethylase (2.5-fold) only and did not produce any increases in total cytochrome P-450 content or NADPH-cytochrome c reductase . No complexed cytochrome P-450 was detected in the azithromycin-dosed rats despite liver concentrations of azithromycin that were 118 times greater than the liver concentrations of erythromycin estolate in erythromycin estolate-dosed rats . Although the short-term oral administration of azithromycin produced hepatic accumulation of the drug and elevated azithromycin demethylase activity, there was no other evidence of hepatic cytochrome P-450 induction or inactivation via cytochrome-metabolite complex formation . In contrast to erythromycin estolate, azithromycin is not expected to inhibit its own metabolism or that of other drugs via this pathway. Eur J Clin Microbiol Infect Dis, 1991 Jun, 10(6), 519 - 24 In vivo activity of the macrolide antibiotics azithromycin, roxithromycin and spiramycin against Toxoplasma gondii; Araujo FG et al.; The macrolide antibiotics azithromycin, roxithromycin and spiramycin were examined in parallel for in vivo activity against Toxoplasma gondii . Azithromycin was considerably more active in protecting mice against death due to acute toxoplasmosis even when the other two antibiotics were used at twice its dose . The higher activity of azithromycin prompted a further examination of its activity against five different strains of Toxoplasma gondii, including two isolated from patients with AIDS . Although variable degrees of protection against death were noted, treatment with 200 mg/kg/day for ten days was sufficient to promote survival of 100% of mice infected with inocula as high as 1 x 10(5) tachyzoites of Toxoplasma gondii . 90% of mice inoculated with 1 x 10(5) tachyzoites of strain MO, isolated from an AIDS patient, and treated orally with 200 mg/kg/day for ten days survived the infection whereas only 40% of mice infected with the same inoculum of the SOU strain, also isolated from an AIDS patient, survived . Tissue concentrations of azithromycin were examined in treated infected and non-infected mice . In both groups of mice azithromycin attained high concentrations in liver, spleen and heart, which exceeded concurrent serum levels by 25- to 200-fold . The concentrations in the brain were almost tenfold higher than the concentrations in serum after treatment with 200 mg/kg/day for ten days . Moreover, the concentrations in brains of infected mice were approximately two-fold higher than in brains of non-infected mice. Am J Obstet Gynecol, 1991 Jun, 164(6 Pt 2), 1794 - 6 The role of azalide antibiotics in the treatment of Chlamydia; Johnson RB; Chlamydia trachomatis causes an estimated 4 million infections each year in the United States . Sequelae in women include infertility and ectopic pregnancy . Doxycycline, the current standard therapy, must be taken twice daily for at least 7 days . Patient compliance is often poor, leading to recurrent disease . Azithromycin, a new antibiotic of the azalide class, achieves high and sustained intracellular levels and demonstrates excellent in vitro activity against C . trachomatis . Reported herein are the results of three comparative clinical trials, which demonstrate that single-dose oral therapy with azithromycin is as effective as a standard 7-day twice-daily course of doxycycline in the treatment of uncomplicated genital infections caused by C . trachomatis. Neurosci Lett, 1991 May 13, 126(1), 67 - 70 Analgesic effects of centrally administered aminoglycoside antibiotics in mice; Ocana M et al.; The possible analgesic effects of i.c.v . administration of several aminoglycoside antibiotics were evaluated in mice using hot plate and tail flick tests . Neomycin (10-80 micrograms/mouse), gentamicin (40-160 micrograms/mouse) and kanamycin (80-320 micrograms/mouse) produced dose-dependent increases in the latencies to forepaw licking and jumping in hot plate test . These drugs also produced dose-dependent increases in the percentage of animals showing analgesia in tail flick test . The order of potency of these aminoglycoside antibiotics in both tests was neomycin greater than gentamicin greater than kanamycin, which is exactly the same order that these drugs show as N-type calcium channel blockers . Bearing in mind this fact and the well known analgesic activity of several drugs which decrease neuronal calcium availability, we suggest that the mechanism of aminoglycoside-induced antinociception may be related to the capacity of these antibiotics to block N-type calcium channels and decrease neuronal calcium availability. Nutr Hosp, 1991 May-Jun, 6(3), 186 - 93 {Complications of intravenous therapy . Influence of parenteral nutrition, central venous pressure and antibiotics}; Armero M et al.; With regard to the controversy on whether the use of central venous catheters for the perfusion of other solutions as well as parenteral nutrition means an increase in the risk of sepsis caused by the catheter, a prospective study was made on 313 central intravenous catheters placed in patients admitted to the Intensive Medicine Unit of La Paz General Hospital over a one-year period . Collection of data on both catheters and patients was done following a protocol applied in all cases . From the results obtained, it can be concluded that in critical patients in whom a single central venous catheter has been placed, this can be used for the infusion of other liquids, apart from parenteral nutrition, without involving an increased risk of sepsis caused by the catheter . This pathology seems to bear more relation to the amount of time the catheter remains in place. DICP, 1991 May, 25(5), 546 - 52 Evaluating the cost impact of intravenous antibiotic dosing frequencies; Foran RM et al.; Cost differences between antibiotic dosing frequencies were studied at Robert Wood Johnson University Hospital . Developing a complete cost profile between antibiotic alternatives is difficult because of role separation within the hospital . To present a more complete profile, the study analyzed the incremental costs associated with the hospital pharmacy and nursing staffs regarding various dosing frequencies, including different iv admixture and administration methods . Results showed that administration of an antibiotic dose costs approximately $3.35 based on labor and material costs associated with admixture and administration . An average of 4.6 minutes/dose saves nurses up to 23 minutes for each patient who receives an antibiotic dosed once rather than six times daily over a 24-hour period . Costs of administration and admixture should be considered in comparisons of combination therapy with monotherapy when deciding between two therapeutically equivalent alternatives. Rev Infect Dis, 1991 May-Jun, 13 Suppl 7, S598 - 607 Evaluation of the immunologic cross-reactivity of aztreonam in patients with cystic fibrosis who are allergic to penicillin and/or cephalosporin antibiotics; Moss RB et al.; The immunogenicity, allergenicity, and cross-reactivity of aztreonam were investigated in 19 patients with cystic fibrosis (CF) who are allergic to beta-lactam antibiotics . Skin tests with benzyl-penicilloyl polylysine (BPO), minor determinant mixture, and the drug responsible for the previous allergic reaction were positive for 26%, 53%, and 79% of the patients, respectively . Serum IgG, but not IgE, antibodies to BPO were detected in nine of 14 patients . Eighteen patients whose skin tests with aztreonam were negative were treated . One developed bronchospasm . The others tolerated aztreonam, with an improvement in clinical score greater than or equal to 1 month after treatment (P less than .001) . One patient without previous exposure had positive aztreonam skin tests and was later treated uneventfully after iv desensitization . Treatment with aztreonam did not result in IgG or IgE antibody responses in vitro . However, two patients had anaphylactic reactions on reexposure . In patients with CF, allergy to beta-lactam antibiotics is primarily drug-specific . But despite reduced immunogenicity and cross-reactivity, aztreonam should be administered cautiously to patients with CF who are allergic to other beta-lactam antibiotics because it is potentially allergenic with repeated use. Am Surg, 1991 May, 57(5), 313 - 6 Peritonitis after cecal perforation . An experimental model to study the therapeutic role of antibiotics associated with allopurinol and catalase; Castillo M et al.; This work uses cecal perforation on the rat as a model of intra-abdominal sepsis . Under these conditions, various antibiotics were tested alone or in association with free radical scavengers, such as allopurinol and catalase . It can be concluded that the scavengers were not effective alone, but when combined with antibiotics they rendered good results in the majority of the groups when given postsepsis . Further studies are needed to determine the real role of agents like the free radical scavengers in infectious situations such as the one discussed here. Biochem Pharmacol, 1991 May 1, 41(9), 1345 - 50 Polyene antibiotics increase the ionic permeability of synaptosomal plasma membranes; Raatikainen O et al.; The effects of antifungal heptaene antibiotics candicidin and amphotericin B were investigated in isolated cerebral cortical nerve terminals (synaptosomes) . The synaptosomes were incubated with candicidin or amphotericin B in the presence or absence of external Ca2+ . Candicidin (0.4-0.8 I.U./mL) increased intrasynaptosomal free Ca2+ significantly . This increase was not significantly suppressed by 30 microM verapamil or 2 microM nifedipine . In the absence of extrasynaptosomal Ca2+ intrasynaptosomal free Ca2+ was not changed by candicidin . Amphotericin B increased intrasynaptosomal free Ca2+ as well . Candicidin (0.05-0.6 I.U./mL) increased the respiration rate up to 3.5-fold above the basal rate . This response was not affected by the absence of extracellular Ca2+ . Ouabain completely blocked the increase of respiration caused by candicidin, whereas tetrodotoxin was ineffective . The plasma membrane depolarized in a dose-dependent manner after candicidin (0.2-0.8 I.U./mL) . The mitochondrial membrane potential was little affected and only at the highest concentrations . The results indicate that heptaene polyenes increase synaptosomal ionic permeability, which is reflected in increased Ca2(+)-influx and accelerated respiration . The increment in synaptosomal free calcium takes place probably as a nonspecific leak via typical polyene-cholesterol channels . The respiration is accelerated by increased Na(+)-permeability through the plasma membrane which stimulates the function of Na+, K(+)-ATPase and thus increases the energy demand. Antibiot Khimioter, 1991 May, 36(5), 5 - 8 {Albofungin formation by a strain isolated as a result of fusion of protoplasts of organisms producing aminoglycoside antibiotics}; Malanicheva IA et al.; Strain 344 synthesizing an antibiotic complex was isolated after fusion of the protoplasts of Streptomyces monomycini producing monomycin and Streptomyces kanamyceticus producing kanamycin . The major component of the complex was identified with albofungin and the minor one was suggested to be chloralbofungin . In the cultures of strain 344 variants forming monomycin were detected . After regeneration of the protoplasts of the parent strains there were isolated no stable clones synthesizing antibiotics differing from monomycin and kanamycin. Antibiot Khimioter, 1991 May, 36(5), 16 - 8 {Experimental estimation of the effect of antibiotics, immobilized on the surface of titanium implant, on the development of the inflammatory process}; Samedov TI et al.; Titanium implants with immobilized lincomycin and ampicillin were studied on rats with respect to the effect on development of inflammatory reactions . The data on the concentrations of sialic acids in the blood during the postoperative period and the histological examinations showed that lower concentrations of sialic acids, early fibroblastic reaction, productive nature of inflammation in the main and rapid formation of the fibrous connective tissue capsule around the implants were the characteristic features and advantages of the use of the implants with the immobilized antibiotics as compared to the use of the routine titanium implants. J Toxicol Clin Exp, 1991 May-Jun, 11(3-4), 163 - 7 {Alveolar paraffinosis . (Apropos of an inhalation pneumopathy resistant to antibiotics in an aged woman)}; Waked M et al.; Case report of an exogenous lipoid pneumonitis fortuitously discovered during acute barbituric intoxication . Discussion about pathogenicity of paraffin oil. Recenti Prog Med, 1991 May, 82(5), 300 - 4 {The ambulatory medical treatment of colonic diverticulitis . An open clinico-endoscopic-histological study with rifaximin, a nonaminoglycoside enteric antibiotic}; Lombardo L et al.; Twenty patients with mild acute diverticulitis of the colon were treated with rifaximine 400 mg b.i.d . per os per 10 days . From a clinical point of view, spontaneous and evoked abdominal pain, diarrhoea, nausea, leukocytosis and hyperthermia resulted in marked significant reduction at the end of treatment, as compared to the basal data (P less than 0.01) . A significant reduction of the peridiverticular oedema, mucosal redness, submucosal haemorrhage and diffuse granular pattern was observed endoscopically at the end of treatment (P less than 0.05) . Only a trend toward degrees of vasodilation and submucosa hemorrhage was observed from the histological point of view . No side-effect was observed during and after the treatment period. J Biochem Biophys Methods, 1991 May-Jun, 22(4), 331 - 6 Effect of dimethyl sulphoxide and some antibiotics on cultured human T-lymphoma cells as measured by microcalorimetry; Lonnbro P et al.; The influence of dimethyl sulphoxide (I), penicillin/streptomycin (II), gentamicin (III), and amphotericin B (IV) on growing human T-lymphoma cells was measured by microcalorimetry . There was a dose-dependent decrease in the heat production rate of the cells after 24 h of incubation with I in concentrations ranging from 0-2% (v/v) . At 3.6%, about half of the cells died . II and III had no effect on the cells after incubation for 6 days, at concentrations from 1 to 10 times that of the normal (50-500 IU/ml; 50-500 micrograms/ml) . IV was used in combination with II (50 IU/ml; 50 micrograms/ml) and III (50 micrograms/ml), respectively, at concentrations between 0.25 and 7.5 micrograms/ml . After 6 days of incubation, the results were similar to those obtained with II and III separately. J Virol Methods, 1991 May, 32(2-3), 163 - 70 The use of antibiotics to control bacterial overgrowth of cell cultures used for diagnostic virology; Gray JJ et al.; Although penicillin and streptomycin are added routinely to cell culture media, bacterial overgrowth has caused a significant problem . A total of 34.4% cell cultures inoculated with specimens, from immunocompromised patients for the isolation of viruses, was discontinued because of bacterial overgrowth . When ceftazidime and vancomycin were added to inoculated cell cultures the overall proportion of contaminated cultures fell from 16.3 to 0.6% (P less than 0.001) . The proportion of cell cultures contaminated after inoculation with specimens from immunocompromised patients fell from 34.4 to 0.4% (P less than 0.001) . At the same time the isolation rate of herpes viruses from specimens submitted from immunocompromised patients increased from 5.2 to 16.4% (P less than 0.001). Invest New Drugs, 1991 May, 9(2), 137 - 48 Adozelesin, a selected lead among cyclopropylpyrroloindole analogs of the DNA-binding