Infection, 1986, 14 Suppl 4, S327 - 31 Clinical efficacy of ofloxacin in the treatment of otorhinolaryngological infections; Baba S; A multi-centered clinical study was carried out to evaluate the efficacy of ofloxacin in otorhinolaryngological infections in Japan . Ofloxacin was used at a dosage of 300 mg to 800 mg daily for three to 20 days in 206 cases of various infectious diseases in the otorhinolaryngological field such as otitis media, external otitis, paranasal sinusitis, tonsillitis and pharyngolaryngitis . Its efficacy rate was 79.9% . Minor side effects were seen in three cases (1.5%), gastro-intestinal disorders in two and headache in one . The antibacterial activity of ofloxacin was compared with the activity of pipemidic acid, nalidixic acid and norfloxacin against clinically isolated microorganisms . Ofloxacin was highly superior to pipemidic acid and nalidixic acid, and slightly more active than or equivalent to norfloxacin. Acta Microbiol Hung, 1986, 33(2), 131 - 40 Comparative laboratory studies on alpha-methoxyimino furyl- and phenylacetamido cephalosporins: structure-activity relationships; Uri JV et al.; Eleven new cephalosporins (three phenylacetamido and eight furylacetamido) containing a methoxyimino group on the 7 beta-acyl side chain and having various substituents at their 3-positions, exhibited similar qualitative, but differing quantitative in vitro antibacterial spectra compared to that of cefuroxime, the first therapeutically used alpha-methoxyimino cephalosporin . The syn-isomers and the alpha-acyl substituted compounds are more active than either the anti-isomer or the beta-acyl substituted compounds . Compounds containing substituted tetrazole rings at the 3-position are likewise more active than those containing other types of substituents in this position . In vivo (mouse) the heterocyclic furylacetamido compounds are more efficacious (protective) than the aromatic phenylacetamido compounds . The furylacetamido alpha-methoxyimino cephalosporins containing at the 3-position the tetrazole group carrying an acidic function possess favorable pharmacokinetic properties, i.e., higher serum levels and prolonged biological half-lives in mouse and squirrel monkey and extensive binding to serum proteins. Comp Immunol Microbiol Infect Dis, 1986, 9(2-3), 155 - 9 Effects of immunopotentiating agents on alveolar macrophage properties; Charley B; Infectious respiratory diseases in man and in domestic animals are characterized by the presence of a large number of different microorganisms: viruses, bacterias, mycoplasmas . It is therefore necessary to stimulate non-specific defense mechanisms in the lung and especially alveolar macrophages (AM) . These cells, located in the alveolar air-spaces, play a major role in the lung clearance mechanisms and exert antibacterial, antiviral and antitumoral activities . Activation of alveolar macrophages was studied in vitro with lipopolysaccharide (LPS), lymphokines or mycobacterial derivatives (MDP) . Rodent alveolar macrophages were rendered cytotoxic by in vitro exposure to LPS, free MDP or liposome-encapsulated MDP derivatives . In vivo, intravenously administered liposomes containing lipophilic MDP derivatives induced cytotoxic alveolar macrophages and protected mice against the development of pulmonary metastases. Scand J Infect Dis Suppl, 1986, 48, 66 - 78 Infection management during antileukemia treatment-induced granulocytopenia: the role for oral norfloxacin prophylaxis against infections arising from the gastrointestinal tract; Karp JE et al.; Aerobic gram negative bacterial infections occur commonly in patients with acute leukemia undergoing intensive chemotherapy-induced bone marrow aplasia, and often arise from the gastrointestinal (GI) tract . The value of oral prophylactic norfloxacin (400 mg every 12 hours) in preventing bacterial infections was determined for 68 adults with acute leukemia by a prospective, randomized, double-blind, placebo-controlled trial . The efficacy of norfloxacin administered prophylactically throughout the course of intensive therapy and deep (less than 100 mm/3), prolonged (median 32 day) granulocytopenia against infections arising from the GI tract was demonstrated by its impact on the clinical manifestations of infection, microbiologically documented gram negative bacterial infections, overall antibiotic management, and GI colonization . Although there was no difference with respect to survival, norfloxacin decreased overall morbidity associated with gram-negative infections, was well tolerated, did not impinge on systemic antibacterial or antitumor therapy, and did not predispose to the development of bacteria resistant either to itself or to multiple other antibiotics . The advantages of norfloxacin relative to other oral agents used for GI prophylaxis and the potential beneficial effects of norfloxacin or overall medical cost are discussed . Oral norfloxacin achieves the goals of GI prophylaxis by effectively suppressing early infection arising from the GI tract and inhibiting GI colonization by multiply resistant pathogens that could give rise to late-onset infections during profound chemotherapy-induced bone marrow aplasia. Eur J Clin Pharmacol, 1986, 30(5), 597 - 605 Dosage adjustment for ceftazidime in patients with impaired renal function; van Dalen R et al.; Ceftazidime has good antibacterial activity against many Gram-negative micro-organisms including Ps . aeruginosa . The aim of the present study was to calculate a dosage adjustment regimen for renal failure patients and to test it in a second group of patients . A study was made of the pharmacokinetics of ceftazidime 1 g given as a single bolus i.v . injection in 20 patients in an intensive care unit with varying degrees of renal function, including patients on regular haemodialysis . The serum half-life of elimination (t1/2 beta) varied from 1.6 to 45 h depending on renal function . During haemodialysis the mean t1/2 was 4.7 h . A good correlation between the renal clearance of creatinine and ceftazidime was observed . In most patients protein binding was lower than previously observed . From the pharmacokinetic data, a dosage adjustment regimen for patients with renal insufficiency was calculated, which studies in 7 further patients showed to be effective. Biol Neonate, 1986, 50(1), 21 - 6 Trace elements and antibacterial activity in amniotic fluid; Honkonen E et al.; Antibacterial activity and trace element concentrations in amniotic fluid (AF) were determined in a population of 39 pregnant women in the second half of gestation . Antibacterial activity in each AF was measured by a spectrophotometric micromethod after 18 h incubation at 37 degrees C using Escherichia coli K 12 as a reference bacterium . Concentrations of zinc, iron, copper, calcium, potassium and bromine were measured by particle-induced X-ray emission method and the zinc concentration was also measured by atomic absorption spectrophotometry . Phosphate concentration was determined by direct albumin adding method . In AFs with good antibacterial activity significantly lower concentrations of potassium and bromine were found when compared to AFs with lower antibacterial activity . Concentrations of zinc, iron, copper, calcium or phosphate did not correlate with antibacterial activity in AF. Zh Mikrobiol Epidemiol Immunobiol, 1986 Jan, (1), 8 - 11 {Rapid diagnosis of exacerbations of chronic bronchitis of pneumococcal etiology in children}; Sakharova AE et al.; The diagnostic possibilities of the microscopic examination of bronchial secretion smears, stained by Gram's method, from 56 children with chronic bronchitis at different stages of exacerbation have been studied . The following criteria have been proposed for confirming the etiological role of pneumococci in cases of endobronchitis in children: the number of paired diplococci in the visual field must exceed 10 with polynuclears covering the whole field . In 84% of cases the use of this method makes it possible to determine the pneumococcal etiology of the disease within two hours from the arrival of the pathological material to a bacteriological laboratory; this method can also be used for evaluating the effectiveness of antibacterial therapy at its different stages. Jpn J Antibiot, 1986 Jan, 39(1), 154 - 8 {In vivo antibacterial activity of cefbuperazone . Synergy of cefbuperazone for bactericidal effect with human polymorphonuclear leukocytes}; Kumasaka Y et al.; Studies were done utilizing E . coli No . 59 which are resistant against human and mouse serum, and the following results were obtained . The therapeutic effect of cefbuperazone (CPBZ) against systemic infections of mice was much higher than that of cefmetazole (CMZ), cefotetan (CTT), latamoxef (LMOX) and cefoperazone (CPZ) . Synergistic bactericidal effect with human polymorphonuclear leukocytes was more marked for CBPZ than CMZ. J Med Chem, 1986 Jan, 29(1), 29 - 40 Synthesis and structure-activity relationships of antibacterial phosphonopeptides incorporating (1-aminoethyl)phosphonic acid and (aminomethyl)phosphonic acid; Atherton FR et al.; Phosphonodipeptides and phosphonooligopeptides based on L- and D-(1-aminoethyl)phosphonic acids L-Ala(P) and D-Ala(P) and (aminomethyl)phosphonic acid Gly(P) at the acid terminus have been synthesized and investigated as antibacterial agents, which owe their activity to the inhibition of bacterial cell-wall biosynthesis . A method for large-scale synthesis of the potent antibacterial agent L-Ala-L-Ala(P) (1, Alafosfalin) is described . Structure-activity relationships in the dipeptide series have been studied by systematic variation of structure 1 . L stereochemistry is generally required for both components . Changes in the L-Ala(P) moiety mostly lead to loss of antibacterial activity, but the phosphonate analogues of L-phenylalanine, L-Phe(P), and L-serine, L-Ser(P), give rise to weakly active L-Ala-L-Phe(P) and L-Ala-L-Ser(P) . Replacement of L-Ala in 1 by common and rare amino acids can give rise to more potent in vitro antibacterials such as L-Nva-L-Ala(P) (45) . Synthetic variation of these more potent dipeptides leads to decreased activity . Phosphonooligopeptides such as (L-Ala)2-L-Ala(P) have a broader in vitro antibacterial spectrum than their phosphonodipeptide precursor, but this is not expressed in vivo, presumably due to rapid metabolism to 1 . Stabilized compounds such as Sar-L-Nva-L-Nva-L-Ala(P) (46) have been developed that are more potent in vivo and have a broader in vivo antibacterial spectrum than the parent phosphonodipeptide. Chemotherapy, 1986, 32(4), 329 - 35 Beta-lactamase stability and in vitro activity of aztreonam, with a comparison to 9 other beta-lactam antibiotics and gentamicin; Friis H et al.; The antibacterial activity of aztreonam, 9 other beta-lactam antibiotics and gentamicin was tested in vitro on 383 recently isolated bacteria . The activity of aztreonam against the gram-negative bacteria is similar to the activity of the 3rd generation cephalosporins and gentamicin . With regard to beta-lactamase stability only PSE-2 out of 14 plasmid mediated beta-lactamases and K-1 out of 2 chromosomally mediated beta-lactamases could hydrolyze aztreonam . With its beta-lactamase stability, high antibacterial activity and narrow-spectrum aztreonam seems to be a valuable addition to the antibiotic arsenal. Infection, 1986, 14 Suppl 4, S258 - 62 Effects of quinolones on granulocyte function in vitro; Boogaerts MA et al.; Granulocytes (PMN) play an important role in antibacterial host defence . The modulation of PMN-function by different antibiotics has been shown previously . Therefore, we investigated the possible immuno-modulatory effects of four new quinolone antibiotics: ciprofloxacin, norfloxacin, pefloxacin, ofloxacin . Pure PMN-preparations were obtained from healthy volunteers and incubated for 30 min at 37 degrees C with the different quinolones at different concentrations (0.1-1-5-10 mg/l) . A complete PMN-functional profile was assayed . At all concentrations tested no significant differences were seen for myeloperoxidase content, superoxide production and chemiluminescence . A significant stimulation of phagocytosis and killing occurred at 10 mg/l of norfloxacin and at 10 mg/l of pefloxacin . An increase of chemotaxis towards formyl-methionyl-leucyl-phenylalanine was noted at 10 mg/l of ofloxacin, while stimulation of hexose monophosphate shunt was seen at 1 mg/l of ciprofloxacin and 10 mg/l of ofloxacin . The mechanism whereby both subinhibitory and inhibitory concentrations of quinolones moderately influence PMN-responsiveness is not yet known . Further studies are needed to elucidate the nature of this quinolone-effect and to assess its relevance in vivo. Antimicrob Agents Chemother, 1986 Jan, 29(1), 163 - 4 Synthesis and antibacterial activities of optically active ofloxacin; Hayakawa I et al.; Two optically active (100% enantiomeric excess) isomers of ofloxacin {(+/-)-ofloxacin; DL-8280; (+/-)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7 H-pyrido{1,2,3-de} {1,4} benzoxazine-6-carboxylic acid} were prepared by use of their optically resolved synthetic intermediates . One of the isomers, (-)-ofloxacin, was 8 to 128 times more potent in inhibiting the multiplication of gram-positive and gram-negative bacteria than the other, (+)-ofloxacin, and approximately two times more active than the racemate, (+/-)-ofloxacin. Chemotherapy, 1986, 32(1), 1 - 6 Study of the diffusion of cefmenoxime into the bronchial secretions; Serieys C et al.; The wide spectrum of antibacterial activity of cefmenoxime as well as its resistance to beta-lactamase degradation, confers upon this drug a probable efficacy in the treatment of common respiratory infections . The objective of this study was to evaluate the penetration of cefmenoxime into bronchial secretions taken in patients, mostly with chronically superinfected bronchial pathology . Bronchial samples were collected by means of fiber-optic bronchoscopy; simultaneous serum samples were also taken after bolus intravenous injection of 1 g of cefmenoxime, after a single dose in 12 patients (group I); after multiple doses in 12 patients (group II) . Concentrations of cefmenoxime were determined by means of microbiological procedure . The results showed: bronchial kinetics of cefmenoxime similar to those of other cephalosporins studied previously; after multiple doses a bronchial steady state with a slow decrease of bronchial levels as a function of time; no difference between levels measured after single or multiple doses; a ratio between bronchial levels (B) and simultaneous serum (S) levels (B/S, %) of about 10% at the 2nd hour, 20% at the 4th hour . Due to the extremely low MICs for most bacteria responsible for respiratory infections, cefmenoxime might be expected as the drug of choice in the treatment of bronchopulmonary infections. J Periodontol, 1986 Jan, 57(1), 29 - 34 Repair of an extensive periodontal defect after tetracycline administration . A case report; Moskow BS; A pathologically migrated maxillary central incisor tooth with a poor periodontal prognosis was treated successfully with conventional periodontal therapy . After almost 4 years, an extensive periodontal lesion developed on the same tooth and extraction was recommended . The patient did not comply and the acute symptoms disappeared after the administration of 1 gm of Tetracycline a day for 2 weeks . Although no definitive periodontal therapy was done, complete resolution of the lesion occurred with the healing of the structures of the periodontium and a dramatic reduction in mobility of the tooth . Antibacterial therapy could be an effective means of treating some periodontal lesions once a more exact and direct association is established between the various clinical forms of periodontitis and specific periodontal or groups of pathogens. Arch Immunol Ther Exp (Warsz), 1986, 34(3), 327 - 31 Structure-activity relationship studies on selected iso-alpha-carbolines . I; Peczynska-Czoch W et al.; In the course of microbial transformation of the antitumor compounds, it has been found that iso-alpha-carbolines and their certain derivatives undergo N-1 methylation by Kitasatosporia setae . The resulting products, iso-alpha-carbolines exhibit antibacterial and antifungal properties in the concentration range of 0.2-2.5 mumol/ml . In the cytotoxicity test only derivatives substituted at C-2 and C-4 display moderate activity against KB cells . None of the compounds tested show a significant inhibitory effect against P388 lymphocytic leukemia. Czech Med, 1986, 9(4), 200 - 2 Control of Pseudomonas sepsis in mice with azlocillin combined with gentamicin; Polivkova L et al.; The antibacterial activity of azlocillin VUFB and gentamicin was tested in vivo . To mice with Pseudomonas sepsis the test substances were injected either alone or combined, and the mortality was assessed . The test substances were freeze dried injectable azlocillin and gentamicin (Pharmachim) . Azlocillin was injected into mice either intravenously or intramuscularly in graduated doses of 50-500 mg/kg once daily . The therapeutic effect was assessed on the basis of survival of the treated mice . Our expectation of a potentiated effect of the azlocillin-gentamicin combination was confirmed . After intramuscular administration of azlocillin plus gentamicin 90% of the mice survived, in comparison with 40% only after either azlocillin or gentamicin alone. Czech Med, 1986, 9(4), 196 - 9 Long-term experience with combined action of antibacterials; Jedlickova Z et al.; The authors have obtained good results in control of respiratory infections in children (aged 3-9 years) (especially those with dg . pneumonia) when applying a combination of amoxicillin with clavulanic acid . Correct indication has enabled them to shorten the period of treatment by means of this combination . The interaction of ticarcillin with some aminoglycoside preparation has been verified in vitro . Synergic action has been found to be high. J Med Chem, 1986 Jan, 29(1), 89 - 95 Peptides of 2-aminopimelic acid: antibacterial agents that inhibit diaminopimelic acid biosynthesis; Berges DA et al.; Succinyl-CoA:tetrahydrodipicolinate-N-succinyltransferase is a key enzyme in the biosynthesis of diaminopimelic acid (DAP), a component of the cell wall peptidoglycan of nearly all bacteria . This enzyme converts the cyclic precursor tetrahydrodipicolinic acid (THDPA) to a succinylated acyclic product . L-2-Aminopimelic acid (L-1), an acyclic analogue of THDPA, was found to be a good substrate for this enzyme and was shown to cause a buildup of THDPA in a cell-free enzyme system but was devoid of antibacterial activity . Incorporation of 1 into a di- or tripeptide yielded derivatives that exhibited antibacterial activity against a range of Gram-negative organisms . Of the five peptide derivatives tested, (L-2-aminopimelyl)-L-alanine (6) was the most potent . These peptides were shown to inhibit DAP production in intact resting cells . High levels (30 mM) of 2-aminopimelic acid were achieved in the cytoplasm of bacteria as a result of efficient uptake of the peptide derivatives through specific peptide transport systems followed, presumably, by cleavage by intracellular peptidases . Finally, the antibacterial activity of these peptides could be reversed by DAP or a DAP-containing peptide . These results demonstrate that the peptides containing L-2-aminopimelic acid exert their antibacterial action by inhibition of diaminopimelic acid biosynthesis. Infection, 1986, 14 Suppl 4, S223 - 5 International experiences with ofloxacin, a new quinolone; Mitsuhashi S; In vitro and in vivo antibacterial activities of ofloxacin, a new quinolone, are presented . Ofloxacin was found to be characterized by potent bactericidal activity due to its strong inhibition of bacterial DNA gyrase . The high antibacterial activity of ofloxacin in vivo was discussed with respect to its physiochemical properties, i.e., hydrophobicity and bioavailability including high serum concentrations and easy entry into bacterial cells. Infection, 1986, 14 Suppl 4, S335 - 7 Safety profile of ofloxacin: the Italian data base; Koverech A et al.; In clinical trials performed in Italy, 2,003 patients, suffering from various infectious diseases, have so far been treated with ofloxacin . In most cases dosages of 200 mg, 300 mg or 400 mg b . i . d . have been used . In all, 130 adverse reactions have been recorded in 116 patients (5.8%): gastrointestinal events (mostly nausea, vomiting and gastric pain) in 4.8% of the patients, neurological events (mostly headache and insomnia) in 0.7%, cutaneous reactions in 0.4% and others in 0.5% cases . The drug-event causal relationship was assessed by the investigators as unlikely in 5.0% of the events, as possible in 47.1%, as probable in 31.4% and as almost certain in 16.5% . The severity of adverse reactions was judged as mild in 55% of the cases, as moderate in 38% and as severe in 7% . In 30 patients (1.5%), treatment was discontinued because of occurrence of side effects . Abnormal laboratory values probably related to treatment were reported in 25 patients (2.1%) . Ofloxacin is well tolerated and shows a safety profile comparable with that of the best tolerated oral antibacterials. Virchows Arch B Cell Pathol Incl Mol Pathol, 1986, 51(1), 39 - 50 The effect of doxycycline on polyvinylpyrrolidone-induced granuloma formation in the rat liver; van den Bogert C et al.; The tetracyclines specifically inhibit mitochondrial protein synthesis when present at the same low concentrations as used for their antibacterial action . Inhibition of mitochondrial protein synthesis leads to decrease in the oxidative energy-generating capacity of cells . Therefore, the presence of tetracyclines may result in proliferation arrest . In the present study we show that continuous intravenous administration of polyvinylpyrrolidone (PVP) induces the formation of granulomas in the normal rat liver; the rats usually die within 2 weeks of continuous PVP treatment . Athymic (nude) rats appear to be more resistent to the deleterious effects of PVP as they survive the treatment for at least 5 weeks . Although the livers of the PVP-treated nude rats are heavily infiltrated with phagocytic cells, they seldom show granulomas . Reconstitution of nude rats with syngenic thymocytes leads, on the other hand, to extensive granuloma formation . Normal rats treated continuously with PVP plus doxycycline, however, all survive, their livers showing only a few very small granulomas and the normal low number of phagocytic cells . We conclude that the formation of granulomas induced by PVP is a process which is mediated by T-lymphocytes . Because doxycycline prevents this kind of granuloma formation it seems likely that doxycycline not only impairs the proliferation and differentiation of T-lymphocytes but also of monocytes and macrophages. Folia Haematol Int Mag Klin Morphol Blutforsch, 1986, 113(5), 696 - 702 Phagocytic activity of human blood platelets examined by electron microscopy; Kemona H et al.; On the basis of a previously elaborated system for testing the phagocytic ability of the human blood platelets we have undertaken studies of testing the interaction between platelet and bacteria during phagocytosis examined by the electron microscope . We have found that during phagocytosis platelets lose their discoid shape and demonstrate numerous pseudopods . During 2 min a complete engulfment of the bacterium could be observed . 10 min after starting phagocytosis it is possible to note partially destroyed bacteria . The role of human blood platelets in the antibacterial mechanisms is briefly discussed. Folia Haematol Int Mag Klin Morphol Blutforsch, 1986, 113(5), 690 - 5 Does the blood platelet phagocytic capacity depend on the sex and plasma thrombopoietic activity? Kemona H, Mantur M, Prokopowicz J. In 16 men and 25 women we tested the phagocytic activity of blood platelets . In women a higher phagocytosis index, increased blood platelet count and lower percentage of phagocytizing cells could be noted in comparison to men . Blood platelet count was significantly higher in women than in men . From this group we chose 10 men and 10 women and determined the plasma thrombopoietic activity . The results obtained were divided into two subgroups A with high and B low plasma thrombopoietic activity . In subgroup A a higher blood platelet count and phagocytosis index and a decreased percentage of phagocytizing platelets in relation to subgroup B could be found . The phagocytic activity of blood platelets in relation to sex and plasma thrombopoietic activity is briefly discussed . The role of blood platelets in antibacterial mechanisms is emphasized. Infection, 1986, 14 Suppl 1, S3 - 15 {Mechanism of action of quinolones}; Smith JT; How do the quinolones inhibit bacteria? The chromosome of bacteria is composed of helical double-stranded DNA and contains 60 to 70 spatial regions of organisation, termed domains of supercoiling . Each domain is about 20 mu long, attached to an RNA core and is organised by supercoiling which occurs quite independently of the DNA coiling in any other domain . Supercoiling is controlled by the enzyme DNA gyrase, which introduces transient breaks into both DNA strands of each domain, removes about 400 turns from its DNA helix, then reseals the DNA so locking in the supercoiling . This supercoiled state is essential to the well-being of bacteria as it enables them to accommodate their chromosome (1300 mu long) within the confines of their cell envelope (2 mu X 1 mu) . The target site of action of the quinolone antibacterial agents is DNA gyrase and its inhibition by them sets off a complex series of events which ultimately causes bacteria to die . However, the bactericidal action of nalidixic acid and most other quinolones can be abolished if protein synthesis is inhibited by chloramphenicol, and perhaps not surprisingly the same is true if RNA synthesis is inhibited by rifampicin . With ofloxacin and ciprofloxacin the situation is more complicated because protein or RNA synthesis inhibition does not completely abolish their bactericidal effects . Hence ofloxacin and ciprofloxacin exhibit a qualitative difference from most other quinolone antibacterial agents in that they possess an additional mechanism of killing bacteria that is not possessed by the older, lesser active drugs . How can these quinolones kill bacteria without harming man? Mammalian cells possess an enzyme which resembles bacterial DNA gyrase in that it cuts double-stranded DNA in a similar manner . However, the mammalian enzyme does not possess any supercoiling action nor is it susceptible to inhibition by the quinolone antibacterials, which can hence be used to inhibit bacteria in man without harm to the latter. Mol Pharmacol, 1986 Jan, 29(1), 52 - 64 The effects of chloramphenicol isomers on the motor end-plate nicotinic receptor-ion channel complex; Henderson F et al.; Four enantiomers of chloramphenicol have been tested for their effects on end-plate current and miniature end-plate current decay and amplitude characteristics in the voltage-clamped costocutaneous nerve-muscle preparation of the garter snake . All four enantiomers exhibited effects on end-plate current and miniature end-plate current decay at similar concentrations (0.2-1.0 mM), indicating that the measured effect was not related to the antibacterial action of the compounds in which D-threo chloramphenicol is known to be at least 50 times more powerful than the L-threo and D- and L-erythro isomers . The compounds slightly increased end-plate current but not miniature end-plate current amplitude, indicating that they produce an increase in end-plate current quantal content . This effect was verified by an analysis of end-plate current driving functions (see Appendix) for one of the chloramphenicol isomers . In addition to this presynaptic action, all four compounds converted end-plate current and miniature end-plate current decays from single to double exponential functions . This effect was both concentration and voltage dependent . For all four compounds, hyperpolarization resulted in a progressive decrease in tau f and an increase in tau s . The relative amplitudes of the fast and slow decay components were independent of membrane potential . The results are interpreted in terms of the drugs blocking the open form of the acetylcholine-activated receptor-ion channel complex . However, in addition to affecting decay characteristics, all four compounds increased the charge passed during both end-plate and miniature end-plate currents . This effect was concentration but not voltage dependent and is inconsistent with the predictions of the sequential model for open ion channel blockade . By using an extension of Ruff's analysis of the sequential model of open end-plate ion channel blockade, we have been able to show that the action of the chloramphenicols on end-plate current amplitude and time course can be explained by the combination of two distinct mechanisms . First is an open channel block conforming to the sequential model and with calculated channel blocking affinity constants ranging from 0.3-1.0 mM . The channel blocking actions of all four isomers were shown to be independent of membrane voltage . Second is an action to slow channel closing, resulting in prolonged open time and hence increased charge passed during the end-plate current . This effect was strongly concentration dependent, but not voltage dependent.(ABSTRACT TRUNCATED AT 400 WORDS) Presse Med, 1985 Dec 21, 14(45), 2291 - 4 {Therapeutic prospects of new fluoroquinolones}; Bryskier A et al.; Fluoroquinolones are new synthetic derivatives with a broad spectrum and a potent antibacterial activity this permits to assimilate these molecules as antibiotics . These compounds are characterized by a quinoline or a naphthyridine nucleus with a fluorine atom in position 6 and a piperazine or a pyrrole nucleus in position 7 . The combination of their antibacterial properties and the good absorption and tissue distribution allows their use in the treatment of the main infections caused by sensitive strains . The clinical and biological tolerance of these drugs are usually excellent. J Chromatogr, 1985 Dec 4, 348(2), 379 - 87 Studies on residual antibacterials in foods . IV . Simultaneous determination of penicillin G, penicillin V and ampicillin in milk by high-performance liquid chromatography; Terada H et al.; A rapid and simple method for the simultaneous determination of penicillin G (PCG), penicillin V (PCV) and ampicillin (ABPC) in milk is described . The retention behaviour of these beta-lactam antibiotics in reversed-phase liquid chromatography with mobile phases containing sodium alkylsulphonate was studied . Good separations were obtained with methanol-water-0.2 M phosphate buffer (pH 4.0) (5:13:2) containing 11 mM sodium 1-heptanesulphonate and a LiChrosorb RP-18 column . The sample was pre-treated with a Sep-Pak C18 cartridge . The peaks corresponding to each beta-lactam antibiotics can be confirmed with the treatment using penicillinase . The recoveries from milk fortified with sodium PCG, potassium PCV and ABCP at levels of 0.5 and 0.1 micrograms/g each were generally better than 87% and the relative standard deviations were 1.17-4.98% . The detection limits corresponded to 0.03 microgram/g of these beta-lactam antibiotics in milk. Zentralbl Bakteriol Mikrobiol Hyg {B}, 1985 Dec, 181(6), 496 - 512 Activity of non antiseptic soaps and ethanol for hand disinfection; Blech MF et al.; This study was done to investigate the antibacterial efficacy of the successive use of non-antiseptic soaps with different pH and ethanol at different dilutions during in-use tests on the natural cutaneous flora for both surgical and hospital hand-washing . The successive combinations of detergents and alcohol were less effective than the use of alcohol alone . The influence of humidity and pH could be taken into consideration . The antibacterial effect of ethanol after hand-washing is relatively slow . Taking into account this delayed effect, the antibacterial action of soap + ethanol is of the same order as that obtained with antiseptic preparations which have more efficient immediate results . The existence of large individual variations during repeated assays suggests an important role of local phenomena in the cutaneous coat . Thus for surgical purposes (= with glove-wearing), the use of ethanol after hand-washing with an acidic soap could be taken into consideration, but for hygienic purposes (= immediate effect, without glove-wearing) the application of ethanol after hand-washing with non antiseptic soap is not advantageous from a bacteriological quantitative point of view. Poult Sci, 1985 Dec, 64(12), 2362 - 7 Pharmacokinetics of sulfamethoxazole and trimethoprim association in hens; Queralt J et al.; A pharmacokinetic study of sulfamethoxazole (SMZ) and trimethoprim (TMP) was carried out on Warren hens after intravenous (iv) dosage of 4:1, and oral administration of dosages of 5:1, and 2.5:1 . The SMZ and TMP half-lives were 8.2 and 2.4 hr, respectively . The ratio between SMZ and TMP serum levels (S/T ratio), after iv administration of the 4:1 dosage, was approximately 20 and remained constant for only 1 hr, while after 5:1 and 2.5:1 oral dosages, the S/T ratio was 40 and 20, respectively, and remained invariable for 12 hr . The oral bioavailability of SMZ and TMP was .46 and .36, respectively . The apparently slower elimination of TMP from serum following oral administration should provide an extended duration of the synergistic antibacterial effect when this route of administration is employed . Finally, the 2.5:1 combination, after oral administration, resulted in an appropriate synergistic ratio (S/T ratio = 20:1) of the drugs in the serum. J Antibiot (Tokyo), 1985 Dec, 38(12), 1752 - 60 Synthesis and antibacterial activity of some derivatives of the antibiotic thermorubin; Cavalleri B et al.; A series of derivatives has been prepared from the antibiotic thermorubin, some of which show a substantial modification of the original structure . The antibacterial activities are reported. J Antibiot (Tokyo), 1985 Dec, 38(12), 1670 - 6 A novel macromolecular antibiotic, SN-07 . Taxonomy of producing organism, isolation, characterization and biological activities; Kikuchi Y et al.; A novel macromolecular antibiotic SN-07 was obtained from the cultural supernatant of Actinomadura roseoviolacea var . miuraensis nov . var . The antibiotic was soluble in water, had a molecular weight of 18,000-22,000 daltons in 50 mM Tris-HCl buffer, pH 7.0, containing 2.0 M KCl as compared with authentic proteins . Its major constituents were nucleic acids . The substance had antibacterial activity against Gram-positive bacteria . It was also effective against lymphocytic leukemia P388 in vivo. Ann Ophthalmol, 1985 Dec, 17(12), 742 - 4 Systemic tetracyclines in the treatment of noninfected corneal ulcers: a case report and proposed new mechanism of action; Perry HD et al.; Corneal melting refers to a condition in patients whose corneas undergo progressive necrosis of stromal tissue despite being culture negative . Recent evidence has shown that systemic tetracyclines demonstrate anti-collagenolytic activity that may have clinical effectiveness in disease treatment . The evidence led us to try this modality as adjunct therapy in the treatment of an 80-year-old white man with a noninfected corneal ulcer . One gram of tetracycline in four divided doses led to a dramatic resolution of the corneal ulcer . This positive result supports the new concept that tetracycline therapy inhibits tissue collagenolytic enzyme activity by a mechanism unrelated to its antibacterial efficacy and may prove useful in the treatment of nonspecific corneal ulceration. Plast Reconstr Surg, 1985 Dec, 76(6), 953 - 63 The use of prophylactic antibacterials in plastic surgery: a 1980s update; Krizek TJ et al.; A questionnaire designed to determine the pattern of usage of prophylactic antibacterials, similar to one used a decade ago, was distributed to plastic surgeons, of whom 1718 responded . The pattern of antibacterial use in 8 major categories and 55 separate operations and circumstances was reviewed . The timing and the influence of various modifying factors was evaluated . The data present the pattern of antibacterial use by plastic surgeons at this point and time, that is, what is "usual and customary". J Med Chem, 1985 Dec, 28(12), 1772 - 9 Synthesis and antibacterial activity of 2,2'-dithiobis(benzamide) derivatives against Mycobacterium species; Okachi R et al.; A series of compounds, which are analogues of 2,2'-dithiobis(benzamide), were synthesized and tested for in vitro antibacterial activity against Mycobacterium tuberculosis H37Rv including resistant strains against streptomycin, kanamycin, or isonicotinic acid hydrazide . MICs of these compounds against atypical mycobacteria, Mycobacterium kansasii and Mycobacterium intracellulare were also examined . Structure-activity relationships were found in a series of (acyloxy)alkyl ester derivatives depending upon the length of alkyl carbon chain . The MIC of the most potent compound, 2,2'-dithiobis{N-{3-(decanoyloxy)propyl}benzamide} {56} was superior or at least equivalent to streptomycin, kanamycin, and ethanbutol . All the compounds showed no cross-resistance between the current antitubercular agents. J Med Chem, 1985 Dec, 28(12), 1870 - 4 Monocyclic pteridine analogues . Inhibition of Escherichia coli dihydropteroate synthase by 6-amino-5-nitrosoisocytosines; Lever OW Jr et al.; A variety of 5,6-disubstituted isocytosine derivatives were evaluated in vitro as inhibitors of dihydropteroate synthase from Escherichia coli . A number of 6-(alkylamino)-5-nitrosoisocytosines have in vitro potency equivalent with or superior to that of therapeutically effective sulfonamide inhibitors of the synthase . The sulfonamide drugs are known to compete for the p-aminobenzoic acid binding site of the synthase, and kinetic analysis of inhibition of the synthase by 6-(methylamino)-5-nitrosoisocytosine (16; I50 = 1.6 microM) and by the 6-(3-phenoxypropyl) amino analogue (33; I50 = 3.7 microM) indicated that the nitrosoisocytosine inhibitors compete with the pteridine substrate for the enzyme . Structure-activity studies demonstrated that the enzyme surface has a low tolerance for steric bulk in the region surrounding the isocytosine 6-amino function . However, this steric intolerance may be counterbalanced to a significant degree by positive allosteric interactions achieved by certain analogues that have a 6-(omega-phenylalkyl)amino substituent . For example, 6-{(7-phenylheptyl)amino}-5-nitrosoisocytosine (28) is as effective an inhibitor (I50 = 1.4 microM) as the 6-methylamino compound 16 . Although several members of the 5-nitroso series were potent synthase inhibitors, none of the nitrosoisocytosines exhibited significant antibacterial activity . This observation may reflect poor transport of these compounds through the bacterial cell wall or, alternatively, may result from a rapid metabolic inactivation process. Scand J Dent Res, 1985 Dec, 93(6), 546 - 54 Comparative antibacterial effectiveness of seven hand antiseptics; Myklebust S; Seven hand antiseptics (alcohol-, iodophor- and chlorhexidine preparations) were compared for antibacterial effectiveness using finger-print contact sampling on blood agar in duplicate series with 18 students as test persons . Bacterial samples were obtained before and after handwashing (with unmedicated liquid soap) as well as after hand disinfection . Hibiscrub was tested without prewashing . The antiseptics were rubbed into the skin and the hands left uncontaminated for 2 min before sampling . Due to results showing unexpectedly low antibacterial effectiveness of 70% (v/v) ethanol, a series of supplementary experiments with ethanol (70% (v/v) and 80% (v/v} and isopropanol (60% (v/v} were performed with 10 laboratory staff-members . These experiments confirmed the previously demonstrated weak antibacterial effect of 70% (v/v) ethanol on the normal hand flora . Alcoholic chlorhexidine solutions and Hibiscrub were the only preparations that gave significant, mean reductions (97.9-99.9% and 80.3-93.4%, respectively) in the number of colony forming units . According to the present study, these are the only test preparations that can be recommended for presurgical hand disinfection, and when hand disinfection is needed in general dental practice. Br J Clin Pharmacol, 1985 Dec, 20(6), 583 - 8 Enoxacin decreases the clearance of theophylline in man; Wijnands WJ et al.; In patients treated concurrently with theophylline and enoxacin, a new broad-spectrum antibacterial agent of the quinolone class, unexpectedly high plasma theophylline concentrations were measured . In part I of this study, daily plasma theophylline concentrations were measured in 14 patients . The mean +/- s.d . theophylline concentrations increased from 8.5 +/- 2.8 micrograms ml-1 prior to enoxacin to a maximum of 21.7 +/- 7.8 micrograms ml-1 during coadministration . In part II, six of these patients received aminophylline intravenously at a constant infusion rate and under controlled conditions . Plasma theophylline concentrations rose from 8.4 +/- 2.4 micrograms ml-1 prior to enoxacin treatment to 15.0 +/- 5.1 micrograms ml-1 at day 3 of coadministration (P less than 0.005) . Plasma protein-binding and renal clearance of theophylline remained unchanged, whereas total body clearance of theophylline significantly decreased (P less than 0.005) . From these observations it is concluded that the rise of plasma theophylline concentrations is caused by a reduced metabolic clearance of theophylline . If concomitant use of both drugs is necessary, monitoring of plasma theophylline concentration and adjustment of the theophylline dose is recommended. Jpn J Antibiot, 1985 Dec, 38(12), 3513 - 9 {Clinical review and antibacterial effect of aztreonam in infections in obstetrics and gynecology}; Fujimoto S et al.; Clinical effect in obstetrics and gynecology was studied on aztreonam (AZT), a potent monobactam antibiotic for Gram-negative bacteria . AZT was tested for 7 cases and effective for all of them with quite a high effective rate of 100% . Neither side effect nor abnormal laboratory findings were noted and it sufficiently proves the property of AZT, a totally chemical-synthesized product with lower incidence of allergic reaction . The above results suggest that AZT is useful for obstetrics and gynecologic infections in view of its high stability to beta-lactamase and dehydropeptidase and high potency against Gram-negative bacteria. J Antibiot (Tokyo), 1985 Dec, 38(12), 1714 - 8 Synthesis and biological activity of (7S)-O-epoxyalkyl derivatives of daunomycinone; Prikrylova V et al.; Synthesis and antibacterial activity of a number of 7-O-epoxyalkyl derivatives of daunomycinone prepared from 7-O-alkenyl derivatives of daunomycinone are described along with their inhibitory effect on leukemia P 388 cells. Jpn J Antibiot, 1985 Dec, 38(12), 3687 - 93 {Pharmacokinetics of aztreonam in peripheral venous serum, uterine arterial serum and intrapelvic female organs}; Miyakawa I et al.; The concentrations of aztreonam (SQ 26,776, AZT, Squibb) in peripheral venous serum, uterine arterial serum and intrapelvic female organs were determined by bioassay, using the cylinder-plate diffusion method, in 27 women with simple total hysterectomy . With an intravenous injection of AZT 1 g, the maximum levels of peripheral venous serum and uterine arterial serum were 76.39 micrograms/ml and 76.38 micrograms/ml, respectively . Also, the biological half-life (T1/2) was 1.56 hours in peripheral venous serum and 1.54 hours in uterine arterial serum . The concentration in uterine arterial serum was more than 1.8 micrograms/ml at 8 hours after injection and maintained at a high level than the minimal inhibitory concentration necessary for most Gram-negative bacteria for at least 8 hours . The concentrations of AZT in female genital organs were kept higher than the minimal inhibitory concentration against E . coli at 4 hours after injection, and the ratios of the concentrations in uterine tube and endometrium to that in peripheral venous serum were 0.40 +/- 0.18 and 0.30 +/- 0.20, respectively . Since AZT is characterized by more potent antibacterial activity against Gram-negative bacteria and the minimal side effects, intravenous administration of AZT at 1 g or 2 g per day may be an adequate dose for infections of the female urogenital tract. J Med Chem, 1985 Dec, 28(12), 1903 - 6 Orally absorbable cephalosporin antibiotics . 3 . Preparation of biologically active R isomer of 7-(3-benzothienylglycylamido)deacetoxycephalosporanic acid; Kukolja S et al.; The methyl and isopropyl esters of (RS)-3-benzothienylglycine were resolved with (+)- and (-)-tartaric acid in acetonitrile to give the corresponding R and S salts . The R-salt 4 was hydrolyzed to (R)-3-benzothienylglycine (5) . The amino group in 5 was protected with the Boc function and the protected R amino acid 6 coupled with the p-NB ester of 7-ADCA to give the diprotected cephalosporin 7 . After removal of the Boc and p-NB groups, the R isomer of 7-(3-benzothienylglycylamido)deacetoxycephalosporanic acid (1) was obtained . The p-NB ester of epimeric cephalosporin 7 was separated by preparative chromatography into R and S isomers . After removal of the protective groups, the S epimer was isolated . The comparison of antibacterial activity of the R and S epimers and the RS mixture of cephalosporin 1 is reported. J Med Chem, 1985 Dec, 28(12), 1886 - 96 Orally absorbable cephalosporin antibiotics . 1 . Structure-activity relationships of benzothienyl- and naphthylglycine derivatives of 7-aminodeacetoxycephalosporanic acid; Kukolja S et al.; A structure-activity relationship study of a number of orally absorbed cephalosporins together with their syntheses is described . These new cephalosporins are benzothienyl- and naphthylglycine derivatives of 7-aminodeacetoxycephalosporanic acid . Several different synthetic methods for the glycine side chains, their protection, and the final acylations are reported . Several of these analogues were more active than cephalexin both in vitro and in vivo against commonly encountered Gram-positive bacteria . (R)-7-(3-Benzothienylglycylamido)-3-methyl-3-cephem-4-carboxylic acid (1R) has emerged as a potent antibacterial agent and is currently undergoing preclinical evaluation. J Hyg (Lond), 1985 Dec, 95(3), 595 - 609 The sub-specific differentiation of Escherichia coli with particular reference to ecological studies in young animals including man; Hinton M; It is possible to differentiate isolates of Escherichia coli using a number of techniques including the determination of the serotype, biotype and phage type and the profiles for resistance to antibacterial agents and toxic chemicals, intracellular enzymes, outer membrane proteins and plasmids and the production of enterotoxin and colicines . These methods have been used principally for the study of pathogenic E . coli and plasmid-mediated drug resistance . However they can also be used successfully for ecological purposes and the application of several of these techniques for the study of the ecology of E . coli in healthy young animals including man is described. Nature, 1985 Nov 14-20, 318(6042), 191 - 4 Isolation, sequence determination and expression in Escherichia coli of the isopenicillin N synthetase gene from Cephalosporium acremonium; Samson SM et al.; The enzyme isopenicillin N synthetase (IPS) catalyses the oxidative condensation of delta-(L-alpha-aminoadipyl)-L-cysteinyl-D-valine (LLD-ACV) to isopenicillin N, which is a central reaction in the pathway to clinically important penicillins and cephalosporins . Here we report the cloning, characterization and expression in Escherichia coli of the gene encoding the IPS protein in Cephalosporium acremonium . The IPS gene was identified by purifying IPS protein, determining the first 23 amino-terminal amino acids, preparing a set of synthetic oligonucleotides encoding a portion of the determined amino-acid sequence, and probing a cosmid genome library with the mixed oligonucleotides . A cosmid hybridizing with the probe was isolated and the IPS gene was localized and sequenced . The IPS gene encodes a polypeptide of relative molecular mass (Mr) 38,416 . When this open reading frame was cloned into an E . coli expression vector and inserted into E . coli, the recombinant E . coli produced a new protein co-migrating with authentic IPS as the major protein of the cell (approximately 20% of cell protein) . Crude cell extracts condensed LLD-ACV to a penicillinase-sensitive molecule whose antibacterial activity indicated that it was isopenicillin N. Vestn Khir Im I I Grek, 1985 Nov, 135(11), 43 - 6 {Antibacterial therapy of liver abscesses}; Aliev VM et al.; An experience with the treatment of 298 patients with parasitogenic (240) and bacterial (58) abscesses is described . Lethality among the first group was 5,4%, among the second group 32,7%. Antimicrob Agents Chemother, 1985 Nov, 28(5), 630 - 3 Antibacterial activities of erythromycins A, B, C, and D and some of their derivatives; Kibwage IO et al.; The MICs of erythromycins A, B, C, and D and some of their derivatives were determined against 21 gram-positive and 15 gram-negative microorganisms . Antibacterial activity was confined to gram-positive and very few gram-negative bacteria . Erythromycin B was somewhat less active than erythromycin A, and erythromycin C and D showed about half that activity or even less . Most other derivatives had negligible activity . Determination of potency by diffusion and turbidimetric assays were in line with MICs . The examination of the results of these assays, however, revealed that there are differences between the data of different laboratories, depending on the microorganisms and conditions used. South Med J, 1985 Nov, 78(11), 1365 - 7 Invasive aspergillosis of the sphenoid sinus manifested as a pituitary tumor; Fuchs HA et al.; Aspergillus infection of the paranasal sinuses is rare but is the most common fungal infection of these structures and should be suspected when sinusitis does not respond to antibacterial drugs . Our case involved the sphenoid sinus, and was initially thought to be a nonfunctioning pituitary tumor . Treatment of Aspergillus sinusitis principally involves surgical debridement, reestablishment of aeration and drainage of the involved sinuses, and adjunctive antifungal chemotherapy. J Am Vet Med Assoc, 1985 Nov 1, 187(9), 944 - 6 Pharyngeal trauma from endotracheal intubation in a colt; Brock KA; A pharyngeal performation, probably associated with endotracheal intubation, occurred in a healthy 4 1/2-month-old colt . Inhalation anesthesia was carried out for elective surgery, but acute cervical cellulitis, pleuritis, and pneumonia developed after the surgery . Antibacterial and supportive therapy was ineffective. Nippon Sanka Fujinka Gakkai Zasshi, 1985 Nov, 37(11), 2369 - 75 {Antibacterial activity of amniotic fluid and lysozyme}; Hagio Y; In order to investigate the antibacterial activity of amniotic fluid, the growth curves of several bacterial species in human amniotic fluid were observed by plate counting methods . The concentration of the bacteriolytic enzyme lysozyme in amniotic fluid was measured, and the relationship between lysozyme and antibacterial activity was discussed . The following results were obtained: Amniotic fluid had an antibacterial effect on B . subtilis, Staph . aureus and E . coli . When amniotic fluid was heated at 100 degrees C for 5 minutes, its antibacterial properties were lost or weakened . The lysozyme concentration in amniotic fluid increased gradually with gestational age, rising to 19.1 +/- 8.3 mu/ml at term . When lysozyme was added to amniotic fluid that had lost its antibacterial properties through exposure to heat, the antibacterial effect on B . subtilis was recovered . The growth of Staph . aureus in amniotic fluid exposed to heat was inhibited by the concomitant addition of lysozyme and aminobenzyl penicillin. J Antibiot (Tokyo), 1985 Nov, 38(11), 1462 - 8 Biphenomycins A and B, novel peptide antibiotics . II . Structural elucidation of biphenomycins A and B; Uchida I et al.; The structures of biphenomycins A and B, novel peptide antibiotics produced by a strain of Streptomyces, have been established as 1 and 2, respectively, on the basis of spectroscopic and chemical evidence . They are unique in that they are cyclic peptides containing a biphenyl moiety included in a 15-membered ring and show potent antibacterial activities especially against Gram-positive bacteria. J Pharmacol Exp Ther, 1985 Nov, 235(2), 418 - 22 Reduced neutrophil superoxide anion release after prolonged infusions of lidocaine; Peck SL et al.; Lidocaine is used extensively in coronary care units, yet the effect of lidocaine infusions on neutrophil function has not been known . Lidocaine and other local anesthetics impair leukocyte antibacterial functions when added in vitro . We found that lidocaine added to human neutrophils in vitro markedly impaired the release of superoxide anion (O2-) and the granule enzymes lysozyme and myeloperoxidase after stimulation by phorbol myristate acetate or opsonized zymosan . We then measured production of O2- during stimulation of neutrophils from eight normal subjects, five coronary artery disease patients not receiving lidocaine and 13 coronary artery disease patients receiving lidocaine infusions for at least 12 hr . Release of O2- by cells from lidocaine-treated patients (14.2 +/- 3.8 nmol/2.5 X 10(6) neutrophils per 15 min) was significantly lower than from cells of the normal subjects (78.4 +/- 7.2 nmol; P less than .001) and the coronary patients not receiving lidocaine (70.6 +/- 4.0 nmol; P less than .001) . Bactericidal assays at a high concentration (2 mg/ml) of lidocaine demonstrated slight reductions in 2 hr killing rates for Escherichia coli (70% with lidocaine vs . 95% control) . Inhibition by lidocaine of the release of toxic oxygen metabolites from neutrophils could potentially reduce infarct size in patients with acute myocardial infarction; but as there is only a slightly reduced ability to kill bacteria, increased susceptibility to infections is unlikely although it cannot be excluded. Drug Metab Dispos, 1985 Nov-Dec, 13(6), 729 - 39 Physiologically based pharmacokinetic model for cefazolin in rabbits and its preliminary extrapolation to man; Tsuji A et al.; In the present study, the physiologically based pharmacokinetic model, which succeeded previously in predicting the pharmacokinetics of beta-lactam antibiotics in rats {A . Tsuji, T . Yoshikawa, K . Nishide, H . Minami, M . Kimura, E . Nakashima, T . Terasaki, E . Miyamoto, C.H . Nightingale, and T . Yamana: Physiologically based pharmacokinetic model for beta-lactam antibiotics . I: tissue distribution and elimination in rats . J . Pharm . Sci . 72, 1239-1252 (1983)}, was applied to cefazolin pharmacokinetics in rabbits and man . After iv bolus dosing in normal rabbits, the time courses of cefazolin concentration in plasma and various tissues (lung, heart, muscle, skin, bone, gut, liver, and kidney) were found to be very similar to those in rats . The values of physiological parameters (tissue plasma flows, tissue volumes, tissue/plasma albumin ratio) and biochemical parameters determined in this study (for nonlinear plasma protein binding, intrinsic renal clearance of active secretion and reabsorption) were incorporated into mass balance equations derived from the model . There was reasonable agreement between the model predictions and the observed data for cefazolin and inulin in rabbits . The model was also successful in the prediction of cefazolin disposition in rabbits with renal failure . Using available information reported for cefazolin in man, a preliminary extrapolation from the present model was attempted, and the overall predicted results after iv administration of 1 g cefazolin in man were compared with the serum and bone tissue data . The length of the effective antibacterial period for the drug is also discussed in terms of its predicted concentration unbound with proteins in various tissue interstitial fluids in man. Vopr Virusol, 1985 Nov-Dec, 30(6), 708 - 10 {Interferonogenicity of the bacterial lysates in human and murine cell cultures}; Zhdanov LV et al.; The antibacterial JRS vaccine was found to be capable of inducing interferon production in human peripheral blood leukocytes and mouse bone marrow cells . The vaccine induced no interferon in L-929 cells or human diploid M-19 cells . Interferon appeared in the culture fluid within 4-6 hours after induction and reached the maximum levels in 18-24 hours . One-hour contact of the vaccine with leukocytes was sufficient for interferon induction . The interferon generated in human blood leukocytes was partially stable at pH 2.2; heating at 56 degrees C for 30 min reduced its activity 4-fold; antiserum to alpha-interferon inhibited it. J Antibiot (Tokyo), 1985 Oct, 38(10), 1387 - 400 Synthesis and structure-activity relationships of 2-azetidinone-1-sulfonic acid derivatives with a heteroatom-bound substituent at the 4-position; Noguchi N et al.; The synthesis and antibacterial activity of 3-{(Z)-2-alkoxyimino-2-(2-aminothiazol-4-yl)-acetamido} -2-azetidinone-1-sulfonic acid derivatives with a heteroatom-bound substituent at the 4-position are described . The effect of various 4-substituents on the antibacterial activity was examined . Some of these compounds showed excellent antibacterial activity especially against Gram-negative bacteria, including beta-lactamase-producing strains. J Antibiot (Tokyo), 1985 Oct, 38(10), 1350 - 8 Chemical modification of spiramycins . VI . Synthesis and antibacterial activities of 3,3''-di-O-acyl-4''-O-sulfonyl and 3,3''-di-O-acyl-4''-O-alkyl derivatives of spiramycin I; Sano M et al.; 3,3''-Di-O-acyl-4''-O-sulfonyl and 3,3''-di-O-acyl-4''-O-alkyl derivatives of spiramycin I were synthesized and evaluated by four parameters, antibacterial activity, affinity to ribosomes, lypophilicity and therapeutic effects . Among them, 3,3''-di-O-acetyl-4''-O-mesyl and 3,3''-di-O-acetyl-4''-O-methylspiramycin I having relatively small substituents at 4''-position were the most effective in mouse protection tests, and the results were comparable to acetylspiramycin. J Antibiot (Tokyo), 1985 Oct, 38(10), 1302 - 12 Inosamycin, a complex of new aminoglycoside antibiotics . I . Production, isolation and properties; Tsunakawa M et al.; A strain of Streptomyces hygroscopicus No . J296-21 (ATCC 39150) was found to produce a complex of new antibiotics, called inosamycins, which consisted of components A, B, C, D and E . They are novel aminocyclitol antibiotics structurally related to neomycin, paromomycin and ribostamycin . The antibiotic complex and each component of inosamycin exhibit a broad antibacterial spectrum but they are inactive against most of the aminoglycoside-resistant organisms . The antibacterial activity of inosamycin A, the major component of the complex, is comparable to that of neomycin but its acute toxicity is significantly lower (ca . 1/3) than that of neomycin. Jpn J Antibiot, 1985 Oct, 38(10), 3065 - 9 {Clinical investigation of ceftizoxime sodium suppositories in pediatric infections}; Tomimasu K et al.; Ceftizoxime suppository (CZX-S) was given to 6 patients, with the following results . The peak serum concentration of CZX was 1.8-7.5 micrograms/ml at 30 minutes after dosing of CZX-S with 9.6-16.7 mg/kg . The antibacterial activity of CZX revealed that the drug can be expected to be effective sufficiently . The overall effect of CZX-S was "markedly improved" in 1 and "moderately improved" in 3 of the 4 patients with pneumonia and "markedly improved" in 1 and "slightly improved" in 1 of the 2 with UTI . CZX-S caused a slight increase in frequency of defecation in 2 of the 6 patients . There were no abnormal findings of symptoms or laboratory test values which were ascribable to side effects. Antibiot Med Biotekhnol, 1985 Oct, 30(10), 770 - 3 {Enhanced activity of the protective factors in patients with suppurative surgical infection using interferon preparations}; Karlov VA et al.; Administration of leukocytic interferon to patients with sepsis and purulent resorptive fever resulted in a reliable increase in the indices of the host protective factors with respect to the infections . Addition of interferon to the surgical and antibacterial treatment promoted a decrease in the periods providing the clinical effect to 19.8 days against 43.8 days in the treatment without interferon. Proc Natl Acad Sci U S A, 1985 Oct, 82(19), 6490 - 1 The structure of caltrin, the calcium-transport inhibitor of bovine seminal plasma; Lewis RV et al.; The amino acid sequence of the bovine seminal protein, caltrin, which inhibits calcium transport into spermatozoa, has been determined . The protein contains 47 amino acid residues . Parts of the sequence are identical with that reported for bovine seminal plasmin, a protein possessing antibacterial activity . We believe the proteins are identical and that the previously reported sequence of seminal plasmin is in error. Biull Eksp Biol Med, 1985 Oct, 100(10), 466 - 7 {Effect of retinoic acid on indices of humoral immunity}; Nozdrin VI et al.; The influence of all-trans- and 13-cys-methylretinoate on antibacterial and antiviral immunity was studied in experiments on noninbred C57Bl/6 and (CBA X C57Bl/6) F1 mice . All-trans-methylretinoate was shown to stimulate the production of antibodies to E . coli antigens, with the effect being dose-dependent . At the same time both compounds inhibited the production of inhibitors, interferon and antibodies to influenza virus. Jpn J Antibiot, 1985 Sep, 38(9), 2571 - 6 {Clinical evaluation on combination therapy of antibiotics and a gamma-globulin preparation (SM-4300) in the field of pediatrics}; Suzuki N et al.; Ten cases of bacterial infections, showing no or insufficient response to antibacterial chemotherapy, were treated with a new intravenous human gamma-globulin (SM-4300) . SM-4300 was administered intravenously (68-172 mg/kg/day) once a day for 1-3 days . SM-4300 was effective in 6 out of 8 pneumonia cases and also in 1 out of 2 septicemia cases . In none of the 10 cases, any side effects were observed. J Antibiot (Tokyo), 1985 Sep, 38(9), 1166 - 70 Glycocinnasperimicin D, a new member of glycocinnamolyspermidine antibiotic; Dobashi K et al.; Glycocinnasperimicin D was isolated from the fermentation filtrate of a strain of Nocardia sp . using various procedures of column chromatography . Glycocinnasperimicin D exhibited broad antibacterial spectrum . Its chemical structure was determined by NMR spectrometric analyses. Int J Clin Pharmacol Ther Toxicol, 1985 Sep, 23(9), 488 - 90 Treatment of dermatological conditions with a combination of an antibacterial agent, an antifungal agent and an antiinflammatory steroid; Franchi G; Thirty-eight patients suffering from dermatological conditions of various natures were treated by means of the simultaneous application of a combination of three creams, the bases of which were sodium fusidate, ketoconazole and clobetasone butyrate respectively . Positive results, in the form of remission of symptoms, were obtained in 86.7% of the cases . Local tolerance was excellent in all cases and no adverse reactions were observed. J Med Chem, 1985 Sep, 28(9), 1371 - 5 Preparation of biologically active ristocetin derivatives: replacements of the 1'-amino group; Herrin TR et al.; A series of ristocetin analogues with modifications (OH, C=O, C=NOH, NCOCH3) at the C-1' amino group was synthesized and found to possess antibacterial activity against gram-positive bacteria and to bind to Ac2-Lys-D-Ala-D-Ala, a model for the antibiotic's site of action . Due to the lack of a positively charged amino group, the active analogues could not form a salt bridge, indicating that an electrostatic interaction between the positively charged 1'-amino group of ristocetin and the carboxylate anion of the peptide is not required for complex formation . The only compound that did not exhibit good antibacterial activity was epiristocetin aglycone (an analogue with the 1'amino group in the opposite configuration (S) as ristocetin) . On the basis of NMR studies of epiristocetin aglycone in solution, the 1'-amino group is located in the proposed carboxylate binding pocket and may sterically block complex formation. J Clin Hosp Pharm, 1985 Sep, 10(3), 289 - 95 The disinfection of silicone-foam dressings; Evans BK et al.; The efficiency of four commonly used antiseptics, chlorhexidine, povidone-iodine, cetrimide and sodium hypochlorite was compared in the disinfection of silicone-foam dressing used in the management of open granulating wounds . An in vitro model was first used to determine the minimum effective concentration of each antiseptic in killing a standard culture of Pseudomonas . The appropriate concentrations were then compared in comparative studies of clinical wounds . Chlorhexidine proved to be the most effective antiseptic, povidone-iodine and cetrimide were moderately successful, but sodium hypochlorite gave poor results . A subsidiary study looked at the problem of wound irritation by carry-over of the antiseptic . A rinse of the dressing after disinfection prevented irritation by chlorhexidine without compromising its antibacterial effect, but this procedure sometimes failed to prevent irritation when using the other antiseptic agents . It is concluded that chlorhexidine is the preferred cleansing agent in the management of silicone-foam dressings on both grounds of bacteriological efficiency and lack of wound irritation . It should be noted that Hibitane concentrate used in this work contains non-ionic detergent and a stabilizing agent . Pure preparations of chlorhexidine may not behave similarly. Arch Ophthalmol, 1985 Sep, 103(9), 1340 - 2 Chemical preparation of the eye in ophthalmic surgery . IV . Comparison of povidone-iodine on the conjunctiva with a prophylactic antibiotic; Isenberg SJ et al.; We previously found that half-strength (5%) povidone-iodine solution significantly reduced the bacterial flora of the conjunctiva . To compare the antibacterial effect of a topical combination antibiotic (Neosporin ophthalmic solution) given three times daily for three days preoperatively with that of half-strength povidone-iodine solution given as part of the preoperative preparation, conjunctival cultures were studied from 35 patients undergoing ocular surgery . When used individually, the antibiotic and povidone-iodine solutions caused a similar and substantial decrease in the number of colonies and species of bacteria cultured . When both drugs were used together, the decrease was even more striking, making 83% of the conjunctivae sterile . To minimize bacterial flora before ocular surgery, we recommend that a broad-spectrum topical antibiotic be given for three days preoperatively and that half-strength povidone-iodine solution be used as part of the preoperative preparation. Int J Dermatol, 1985 Sep, 24(7), 441 - 3 Pustular acne; Piamphongsant T; Pustules from 92 new cases of pustular acne and gram-negative folliculitis were cultured in aerobic medium for superimposed bacterial infection . During the treatment of 1,561 new patients with papular acne with tetracycline and topical clindamycin and antibacterial soaps, an additional 10 developed pustules . The majority showed in vitro resistance to ampicillin . The effective treatment was co-trimoxazole and topical gentamicin . A new classification of acne with practical therapeutic use is needed. J Hosp Infect, 1985 Sep, 6(3), 299 - 303 A comparison of the in vivo antibacterial effects of 'OpSite', 'Tegaderm' and 'Ensure' dressings; Holland KT et al.; Three semi-permeable polyurethane dressings, 'Ensure', 'OpSite' and 'Tegaderm', were tested for their ability to prevent the increase in bacterial population under naturally hydrated, occluded volar forearm skin . Only 'OpSite' inhibited the bacterial multiplication in these tests . It is concluded that in the practical situation, 'OpSite' could well confer a greater margin of safety. Antimicrob Agents Chemother, 1985 Sep, 28(3), 437 - 9 Antibacterial activities of antineoplastic agents; Bodet CA 3rd et al.; Fourteen antineoplastic agents were examined for in vitro antibacterial activity against 101 aerobic and anaerobic bacterial isolates representing indigenous human microflora and selected opportunistic pathogens . Only 5-fluorouracil, mitomycin, and etoposide demonstrated inhibitory effects at achievable plasma concentrations, while the remaining drugs lacked appreciable antibacterial activities. Pharmazie, 1985 Aug, 40(8), 570 - 1 {Effect of new quaternary imino compounds against selected bacterial and fungal strains . 11 . Synthesis of 1-methyl- and 1-ethyl-3-(n-alkoxymethyl)imidazolium chlorides}; Pernak J et al.; Syntheses and antibacterial activity of the imidazolium compounds are described . Syntheses of the imidazolium chlorides were performed by reaction of 1-alkylimidazole with chloromethylalkyl ether . Antibacterial properties of obtained compounds was tested on 13 strains of bacteria and fungi . Chlorides with n-dodecaoxymethyl radical indicated the best antibacterial activity. Antibiot Med Biotekhnol, 1985 Aug, 30(8), 609 - 14 {Bacteriological indications for the choice of antibacterial preparations in the cancer clinic}; Smolianskaia AZ et al.; Opportunistic microorganisms with multiple drug resistance are the main causative agents of infectious complications in oncological patients . The spectrum of the causative agents and their antibiotic sensitivity change with introduction of new drugs . This requires constant control over the composition of the causative agents and their sensitivity . Such a control provides rational antibacterial therapy when the causative agent is in virtue of some reasons unknown or the bacteriological data are not available . The prophylactic use of antibacterial drugs is of limited value, largely in operations on the gastrointestinal tract and other naturally contaminated cavities. Sabouraudia, 1985 Aug, 23(4), 303 - 12 Prevalence of bacteria and fungi in athlete's foot of varying severity and response to topical antibacterial and antifungal therapies; Talwar P et al.; Ninety-six patients with clinical evidence of interdigital lesions classified as mild, moderate and severe athlete's foot were investigated for bacterial and fungal populations in the interspaces . Gram-negative bacteria, which were not found in the toe spaces of 50 normal controls, were grown in increasing numbers and with increasing frequency as the symptoms progressed from mild to severe . Gram-positive bacteria were also isolated regularly and in increasing numbers commensurate with the severity of the disease . Similarly the isolation rates of dermatophytes and Candida species were higher in patients with moderate and severe disease compared to those with mild disease . Clinical and culture responses to topical applications with framycetin, tolnaftate, miconazole and clotrimazole were also studied . In some patients the prevalence of pathogenic fungi increased as bacterial numbers decreased . The pure antibacterial framycetin brought symptomatic relief, as did the purely anti-dermatophyte substance tolnaftate, but best results were seen with two azole compounds having mixed antibacterial and antifungal properties. J Antibiot (Tokyo), 1985 Aug, 38(8), 1061 - 7 Synthesis and in vitro activity of some methylenomycin analogs; Tius MA et al.; A cationic cyclopentannelation reaction has afforded a very simple route to a wide variety of methylenomycin analogs . The antibacterial activity of these readily accessible synthetic compounds parallels that of naturally occurring methylenomycin A . The in vitro antitumor activity of the synthetics assayed using human nasopharyngeal carcinoma (KB) cells is particularly promising. Am Rev Respir Dis, 1985 Aug, 132(2), 409 - 16 Mutational resistance as the mechanism of acquired drug resistance to aminoglycosides and antibacterial agents in Mycobacterium fortuitum and Mycobacterium chelonei . Evidence is based on plasmid analysis, mutational frequencies, and aminoglycoside-modifying enzyme assays; Wallace RJ Jr et al.; Possible mechanisms of drug resistance of Mycobacterium fortuitum and Mycobacterium chelonei to antibacterial agents were investigated . Single-step mutational frequencies were low (generally less than or equal to 10(-7} for cefoxitin, doxycycline, erythromycin, and sulfamethoxazole and relatively high (10(-4) to 10(-7} for kanamycin and amikacin . Aminoglycoside-susceptible strains of both species contained an aminoglycoside acetyltransferase (3)-III or IV . No additional enzymes were seen with laboratory or clinically acquired aminoglycoside resistance . Plasmids of several sizes were present in some susceptible isolates of both species, but acquired resistance was not associated with a change in the apparent size or number of these plasmids . Isolates with acquired resistance to amikacin were resistant to the other 2-deoxystreptamine aminoglycosides but showed little or no change in minimal inhibitory concentrations to streptomycin, suggesting either a difference in cellular uptake between the 2 groups of drugs or, more likely, different binding sites on the ribosome . In 59 patients treated with 63 courses of therapy with a single agent for 1 month or longer, the development of resistance was observed only twice (3%) . Both isolates had high mutational frequencies (10(-4) and 10(-5} . These studies support mutational resistance as the mechanism of acquired resistance to antibacterial agents in M . fortuitum and M . chelonei. Semin Urol, 1985 Aug, 3(3), 193 - 9 Evaluation and treatment of unconventional genitourinary tract infections; Krieger JN; It is fashionable to treat infections ascribed to unusual organisms, particularly in patients who don't improve following conventional antibacterial drug therapy . Unfortunately, all patients who meet this commonly used clinical definition are not infected with unusual organisms . Therefore, every effort should be made to actually identify a pathogen prior to initiating therapy . Specialized culture media or methods for direct identification of organisms in clinical specimens are necessary for accurate diagnosis . Fortunately, increased understanding of the microbiology of these organisms and improvement in diagnostic techniques should greatly improve the accuracy of clinical diagnosis . Precise diagnosis is important as a guide to specific therapy . In addition, many "unusual" infections are caused by organisms that are transmitted by sexual contact . The concept of sexually transmitted diseases is primarily clinical and not microbiologic in nature . The concept of sexually transmitted diseases represents a common mode of transmission for a wide variety of infectious diseases . The pathogens span the full spectrum of medical microbiology . From the biologic standpoint these organisms have few common characteristics aside from the ability to colonize and, on occasion, invade particular anatomic sites . Many sexually transmitted pathogens are fastidious organisms with exacting growth requirements . Such pathogens are susceptible to death in conditions outside of their usual habitat . Thus, diagnosis of many sexually transmitted pathogens requires both a high index of clinical suspicion and careful processing of clinical specimens . The concept of sexually transmitted diseases has important epidemiologic implications . Patients with one sexually transmitted disease are frequently infected with other sexually transmitted pathogens . Therefore, it is important to evaluate patients for multiple organisms transmitted by a similar mechanism.(ABSTRACT TRUNCATED AT 250 WORDS) Farmaco {Sci}, 1985 Aug, 40(8), 555 - 64 {Quantitative structure-activity relationship of quinoline derivatives}; Gomez Contreras F et al.; Quantum-chemical computations using the Huckel method have been performed on quinoline derivatives that exhibit antibacterial activity against E . coli, in order to obtain quantitative structure-activity relationship and drug-receptor interaction data. J Dairy Res, 1985 Aug, 52(3), 379 - 89 Effect of ACTH and oxytocin treatment on lactoferrin and citrate in cows' milk; Thomas AS et al.; Six dairy cows were treated before milkings with either oxytocin (Pitocin, 20 i.u.) or ACTH (Synacthen, 150 i.u.), principally to determine their effect on the ratio of citrate: lactoferrin concentrations in the milk . With ACTH treatment, after 3 d milk yield and citrate concentration decreased significantly, lactoferrin and bovine serum albumin (BSA) concentrations increased significantly . Somatic cell counts (SCC) increased temporarily in the milk of three of the cows which previously had greater than 100 000 cells/ml . Lactoferrin yield remained fairly constant but citrate yield was significantly reduced . The citrate: lactoferrin molar ratio decreased from 1373 to 606 . With oxytocin treatment, after 4 d milk yield first increased and then significantly decreased, citrate concentration decreased significantly while there were no significant changes in lactoferrin or BSA concentration or in the yield of any other milk constituents . The citrate: lactoferrin molar ratio decreased from 1621 to 1301 . There were no significant changes in SCC either during treatment or 4 d after treatment but there was a significant rise at 16 d after treatment . It was concluded that in lactating cows both hormones affected citrate and lactoferrin concentrations in the direction that would improve the antibacterial properties of milk, but that this was accompanied by adverse effects on milk secretion . The extent of the change was not sufficient to be likely to produce inhibition of coliform bacteria. Biochim Biophys Acta, 1985 Jul 5, 840(3), 383 - 92 Kinetics of dissociation of nogalamycin from DNA: comparison with other anthracycline antibiotics; Fox KR et al.; Stopped-flow spectrometry and simple mixing techniques have been employed to investigate the detergent-induced dissociation of anthracycline antibiotics from natural and synthetic DNAs . Both daunomycin and nogalamycin dissociate more slowly from poly(dG-dC) than from poly(dA-dT) but the difference is much more marked for nogalamycin . With an equimolar mixture of poly(dG-dC) and poly(dA-dT), or with poly(dA-dC).poly(dG-dT), dissociation of nogalamycin occurs very slowly . In all cases the release of antibiotic from a synthetic polynucleotide is a one-step process following a single exponential . Dissociation of daunomycin, adriamycin and iremycin from calf thymus DNA is a more complex reaction which requires a two-exponential fit, in contrast to earlier reports, but differences between the behaviour of the three antibiotics are minor . Dissociation of nogalamycin from natural DNA requires a three-exponential fit, is in general far slower, and depends upon the base composition, the level of binding and the time allowed for the complex to equilibrate . It is concluded that sequence selectivity is minimal or lacking for daunomycin, whereas nogalamycin binding is sequence dependent and probably involves migration of the antibiotic between DNA binding sites . There is an inverse correlation between dissociation rate constants and antibacterial potency in simple tests. J Antimicrob Chemother, 1985 Jul, 16 Suppl A, 217 - 20 The penetration of macrolides into bronchial secretions; Pierre J et al.; Macrolides have shown efficacy in the treatment of a large range of respiratory infections . These antibiotics are well tolerated, have a narrow antibacterial spectrum, and excellent diffusion properties . We have studied the penetration into bronchial secretions of three macrolides, erythromycin, josamycin and oleandomycin . The bronchial concentrations of erythromycin reached an average of 1 mg/l 2 h after oral administration of 1 g; they were lower for josamycin (0.52 mg/l) but the ratio between bronchial and simultaneous serum concentrations was similar for both drugs . Bronchial levels of oleandomycin were rapidly higher than the serum levels, reaching 3 to 4 mg/l, a ratio of more than 100% . Other studies on tissue concentrations of erythromycin and josamycin showed local levels of 4 to 6 mg/l, whereas in bronchial secretions the concentrations were identical to those measured in our study . On the whole, the good diffusion of macrolides into respiratory tissues and secretions as well as in-vitro antibacterial activity against most species responsible for respiratory infections confirm their indication in the treatment of these infections. Int J Clin Pharmacol Ther Toxicol, 1985 Jul, 23(7), 373 - 5 Use of a combination of an anti-inflammatory corticosteroid, an antibacterial agent and an antifungal in the local post-operative treatment of cutaneo-mucosal diseases following cryosurgery; Gini M; Forty-two patients undergoing cryosurgery for skin diseases were treated by means of the simultaneous application of three creams, the respective bases of which were beclomethasone dipropionate, sodium fusidate and ketoconazole . The treatment produced excellent results, preventing bacterial and/or mycotic superinfections and relieving the edema and erythema caused by the operation in 97.6% of cases . Local tolerance was optimal in all cases; no adverse reactions of any kind being reported. Int J Clin Pharmacol Ther Toxicol, 1985 Jul, 23(7), 367 - 72 Clinical results obtained with a combination of an anti-inflammatory steroid, an antibacterial agent and an antifungal in dermatological outpatient practice; Pazzaglia A; Forty outpatients with skin diseases were treated with an extempore combination of three creams, the respective bases of which were beclomethasone dipropionate, sodium fusidate and ketoconazole . Positive results were obtained in 97.5% of the cases with good relief of symptoms and excellent local tolerance in all cases treated. J Med Chem, 1985 Jul, 28(7), 960 - 3 4-Deoxypyrido{1',2':1,2}imidazo{5,4-c}rifamycin SV derivatives . A new series of semisynthetic rifamycins with high antibacterial activity and low gastroenteric absorption; Marchi E et al.; A series of 4-deoxypyrido{1',2':1,2}imidazo{5,4-c}rifamycin SV derivatives (6-11) were prepared that demonstrated high antibacterial activity suitable for an intestinal disinfectant . These compounds are zwitterionic in nature and are poorly absorbed through the gastroenteric tract but maintain the ability to cross the bacterial cell wall . X-ray crystallographic data are presented to demonstrate the zwitterionic nature of these compounds . The structure-activity relationship of this novel series of antibiotics is discussed and the derivative with the highest ratio between subcutaneous and oral activity (6) was selected for clinical development . At the outset of this work several 3-(quaternary ammonium bromides) (1-5) were prepared and tested for antibacterial activity . These compounds were demonstrated to be too polar to even cross the bacterial cell wall but led to the synthesis of 6-11. Infect Control, 1985 Jul, 6(7), 283 - 8 The rapidly growing mycobacteria--Mycobacterium fortuitum and Mycobacterium chelonei; Brown TH; In summary, rapidly growing mycobacteria, M . fortuitum and M . chelonei, are pathogens of increasing importance which are often hospital-acquired and can infect patients with iatrogenic immunosuppression . They readily grow on routine mycobacterial culture media and must be distinguished from non-pathogenic rapidly growing species and slowly growing mycobacteria . Widely distributed in nature, they are often present in hospital environments, especially in water . Compared to M . tuberculosis they are weak pathogens, and infected patients are not considered contagious . Disease is probably acquired from environmental sources by direct entry of the organisms through traumatized skin or mucous membranes or by aspiration into previously abnormal lungs . They are usually resistant to antituberculous agents but are susceptible to several commonly used antibacterial agents . Treatment generally requires one or more active antibiotics plus adjunctive surgery in many cases . Prevention of nosocomial infection lies in proper disinfection of potentially contaminated medical devices and elimination of contaminated water. J Biol Chem, 1985 Jun 25, 260(12), 7174 - 7 Primary structure of sarcotoxin I, an antibacterial protein induced in the hemolymph of Sarcophaga peregrina (flesh fly) larvae; Okada M et al.; The primary structure of sarcotoxin I, a potent bactericidal protein induced in the hemolymph of larvae of Sarcophaga peregrina (flesh fly), was investigated . Sarcotoxin I was a mixture of three proteins (sarcotoxins IA, IB, and IC) with almost identical primary structures . These proteins were found to consist of 39 amino acid residues and to differ in only 2-3 amino acid residues . The amino-terminal half of the molecules was rich in charged amino acids and was hydrophilic, whereas the carboxyl-terminal half was hydrophobic . It is suggested that the carboxyl-terminal half of sarcotoxin I penetrates into the bacterial membrane and that its amino-terminal half rich in basic amino acid residues interacts with acidic phospholipids in the bacterial membrane, resulting in perturbation of the membrane and loss of viability of the bacteria. Hosp Formul, 1985 Jul, 20(7), 802 - 5, 808 New cephalosporin antibiotics: selection and uses; Shibl AM et al.; The new third-generation cephalosporins have an improved antibacterial spectrum and are agents of choice for the treatment of many gram-negative pathogens . With the introduction of these cephalosporins, questions on their indications and use need to be considered . It is especially important that they be saved for special situations in which their capabilities are required, which will prevent the development of widespread resistance and superinfection . A clinical summary of the new cephalosporins is provided, with emphasis on the situations in which they are agents of choice. Antibiot Med Biotekhnol, 1985 Jun, 30(6), 456 - 9 {Laboratory methods of controlling the effectiveness of antibacterial therapy}; Treskina OS et al.; The serum antibacterial activity (SAA) against causative agent isolated after the use of antibiotics was studied in 68 patients with pyoseptic diseases . The SAA ranged from 1:2 to 1:512 and depended on the antibiotic sensitivity of the causative agents . Antibiotic therapy was effective, when the SAA was equal to 1:8-1:512 . With the use of monotherapy the adequacy of the regimens was controlled by the relation between the maximal blood level of the antibiotic and its MIC for the causative agent . The favourable clinical effect of the treatment with aminoglycosides and beta-lactams corresponded to the SAA exceeding 4. Zh Mikrobiol Epidemiol Immunobiol, 1985 Jun, (6), 72 - 5 {Enzyme profile in the peripheral blood leukocytes in acute respiratory diseases}; Braude NA et al.; The character of changes in the enzymatic activity of peripheral blood leukocytes indicate the activity and severity of the process and may serve as data for the prognosis of the course of the disease and for the evaluation of the effectiveness of antibacterial and desensitizing therapy. J Antimicrob Chemother, 1985 Jun, 15 Suppl C, 1 - 4 Synthesis and preliminary in-vitro profile of Sch 34343--a new penem antibacterial agent; Ganguly AK et al.; Sch 34343, a new penem antibiotic, has been synthesized by several routes and found to be highly active against both aerobic and anaerobic Gram-positive and Gram-negative organisms (except Pseudomonas) . It has excellent beta-lactamase stability and is bactericidal . The synthetic routes to Sch 34343 and its in-vitro activity compared with other structurally related penems are discussed. Antimicrob Agents Chemother, 1985 Jun, 27(6), 897 - 902 Attenuation of experimental tobramycin nephrotoxicity by ticarcillin; English J et al.; It is well known that in vitro the combination of carbenicillin, ticarcillin, or other antipseudomonal penicillins with gentamicin, tobramycin, or other aminoglycoside antibiotics results in the inactivation of the antibacterial activity of the aminoglycoside . To assess the influence of the in vivo interaction of tobramycin and ticarcillin on experimental nephrotoxicity, male Fischer 344 rats were given either tobramycin alone (120 mg/kg per day), tobramycin (120 mg/kg per day) and ticarcillin (250 mg/kg per day) concomitantly, or the combination of these drugs at the same doses that had been preincubated for 24 h and at the time of delivery contained but 63 and 25%, respectively, of the initial concentrations of tobramycin and ticarcillin as measured by conventional analytical procedures . Initial experiments were conducted to determine the concentrations of the antibiotics in serum achieved after administration of each test solution . After a single dose of the test solution, ticarcillin concentrations in serum were higher and more prolonged in rats given tobramycin plus ticarcillin than in rats given ticarcillin alone . After 7 days of exposure to the test solutions, inulin clearance in animals given tobramycin alone was 0.15 +/- 0.1 (mean +/- 2 standard errors) ml/min per 100 g of body weight as compared with 0.53 +/- 0.1 in rats given tobramycin and ticarcillin concomitantly, 0.59 +/- 0.1 in animals given the partially inactivated tobramycin-ticarcillin mixture, and 0.79 +/- 0.1 in control rats . Although there was some improvement in inulin clearance in the group containing tobramycin alone, the three treatment groups maintained the same rank relationship in inulin clearance through 14 days of treatment . Real histology confirmed the attenuation of tubular injury in animals given tobramycin and ticarcillin concomitantly . There was no evidence of toxicity from the presumed inactivation complexes of tobramycin-ticarcillin . These results document an in vivo protective effect of ticarcillin on experimental tobramycin nephrotoxicity. J S Afr Vet Assoc, 1985 Jun, 56(2), 101 - 2 A haemorrhagic syndrome in recently weaned pigs ascribed to hypovitaminosis K; Newsholme SJ et al.; An outbreak of a haemorrhagic syndrome involved recently weaned, mixed-breed pigs in a large piggery . The pigs were fed a pelleted complete ration containing antibacterial drugs . Affected pigs failed to grow, became pale and developed large, subcutaneous haematomas . Some pigs became lame and one had epistaxis . The monthly mortality rate in the weaner house, which was previously less than 2%, exceeded 6% during the outbreak . Coagulation time, activated partial thromboplastin time and prothrombin time were prolonged in blood from some of the pigs . The outbreak resolved promptly after supplementation of the diet with vitamin K3. J Infect Dis, 1985 Jun, 151(6), 1123 - 9 Isolation of an antibacterial peptide from human lung lavage fluid; Ellison RT 3rd et al.; The contribution of extracellular secretions to the antibacterial defenses of the lungs remains poorly defined . Recent studies have demonstrated that mouse and rabbit bronchoalveolar washings contain a low-molecular-weight peptide that has antibacterial activity against Escherichia coli . In this study we investigated whether a similar peptide could be identified in human secretions . Bronchoalveolar lavage fluid was obtained from normal volunteers and patients with interstitial lung disease or pulmonary alveolar proteinosis . Cellular material and surfactant lipids were removed from the fluid by sequential centrifugations, and the supernatant was fractionated by exclusion filtration to isolate peptides with a molecular weight less than 10,000 . Gel filtration chromatography separated the ultrafiltrate into several peaks, the first of which had antibacterial activity against E . coli . This material was further separated into several hydrophilic peaks by reverse-phase high-pressure liquid chromatography (RPHPLC) . All samples had similar RPHPLC graphs . Material from the third RPHPLC peak produced an antibacterial effect similar to that produced by the rabbit and mouse peptide. Int J Clin Pharmacol Ther Toxicol, 1985 Jun, 23(6), 326 - 8 Local and general treatment with ceftazidime as monotherapy in central nervous system infections and in septicemic infection; Fiori GP et al.; Twenty-three patients (mean age: 47 years; range: 4 months to 79 years) admitted to Varese Regional Hospital over the period from October 1983 to March 1984 and suffering from severe infections of a septicemic nature were treated with ceftazidime . All patients had previously received other broad-spectrum antibacterial agents . Isolation of causative pathogens and evaluation of their susceptibility to ceftazidime justified use of the drug as monotherapy . Ceftazidime was administered intravenously at the mean dose of 60-120 mg/kg/day . In some cases, it was injected directly into the renal parenchyma (2 g/day) or into the cerebral ventricles (1 mg/kg/day) . Local and systemic tolerance were optimal in all cases, no significant side effects being observed . Eradication of pathogens was excellent and clinical outcome satisfactory in all patients. J Pediatr, 1985 Jun, 106(6), 1035 - 42 Management in the febrile, neutropenic patient with cancer: therapeutic considerations; Brown AE; Infection is the principal cause of death in neutropenic children and adults with neoplastic diseases . Various antibiotic regimens have been studied in clinical trials in an attempt to reduce this mortality . Recent trials have compared newer combinations of antibacterial agents (double beta-lactams) or monotherapy with the standard aminoglycoside-beta-lactam combinations . No significant differences are demonstrated in these trials with regard to efficacy . Emphasis has been on the reduction of toxicity . Although nephrotoxicity, ototoxicity, and hypokalemia have been of concern in the past and continue to be important, newer problems have emerged that involve disorders of coagulation, for example, prolongation of prothrombin time, disorders of platelet function, and clinical bleeding . Superinfection and the emergence of resistance during therapy have also been problematic . Cost must be considered an important factor in determining the selection of an antibacterial regimen . The combination of an aminoglycoside and a beta-lactam antibiotic remains the standard against which future combinations or monotherapy must be judged in clinical trials involving the febrile, neutropenic patient with cancer. Infect Immun, 1985 Jun, 48(3), 607 - 10 Lack of antibacterial activity after intravenous hydrogen peroxide infusion in experimental Escherichia coli sepsis; Shenep JL et al.; The intravenous administration of hydrogen peroxide has been reported to benefit patients with pneumonia and to reduce Plasmodium parasitemia in experimentally infected mice . We assessed the antibacterial activity of intravenously infused hydrogen peroxide against hydrogen peroxide-susceptible Escherichia coli (MBC of hydrogen peroxide, 0.23 mM) in experimentally infected rabbits . No decrease in the level of bacteremia was detected at the maximum intravenous infusion rate of hydrogen peroxide physiologically tolerated by the rabbits (2.0 mumol/h) . Moreover, the addition ex vivo of greater amounts of hydrogen peroxide to human or murine blood containing E . coli resulted in no detectable antibacterial action . In contrast, ethyl hydrogen peroxide, which is not affected by catalase, was bactericidal when added ex vivo to human blood containing E . coli . These results suggest that extracellular hydrogen peroxide, whether of exogenous or endogenous origin, does not have antibacterial activity in the blood of animals having even low levels of catalase. Acta Ophthalmol (Copenh), 1985 Jun, 63(3), 341 - 5 The concentration of lactoferrin in tears during post-operative ocular inflammation; Jensen OL et al.; Tear concentration of lactoferrin (LF) was measured by an ELISA technique and followed in 25 patients undergoing cataract surgery . The pre-operative concentration of LF in tears was 773 +/- 60 micrograms/ml (+/- SE) (range: 407-1514 micrograms/ml) . On the first day following surgery, there was a significant decrease in tear LF concentration to 377 +/- 45 micrograms/ml followed by a gradual return to the initial value during a post-operative observation period of twelve days . There was an inverse linear relationship between the LF concentration and the tear secretion rate measured by a modified Schirmer I test (1 min) suggesting a constant LF secretion rate by the tear glands . The contribution of LF from neutrophils to the tear fluid seems to be of minor importance . Since LF has known antibacterial and anti-inflammatory effects, our results may contribute to a further understanding of the microbial vulnerability or resistance of the eye following surgical procedures. Scand J Dent Res, 1985 Jun, 93(3), 222 - 6 Importance of teeth and tongue as possible receptor sites for chlorhexidine in relation to its clinical effect; Waaler SM et al.; Teeth have previously been shown not to be of any major importance when quantitatively measuring the retention of chlorhexidine in the oral cavity . Only a few studies have examined the significance of the binding of chlorhexidine to the tongue in relation to its plaque inhibiting effect . The present study was therefore carried out to further examine these possible chlorhexidine receptor sites in the oral cavity in relation to its known antibacterial effect at the teeth surface . Two daily applications of chlorhexidine on the teeth in the right side of the maxilla, against a contralateral water control, both in combination with a sucrose challenge six times daily, showed no significant reduction of plaque formation when compared to an application of sucrose used alone . Two daily applications of chlorhexidine on the tongue, again combined with sucrose challenge, also showed no significant plaque inhibiting effect . The results obtained indicate that neither the teeth nor the tongue seem to be of major importance as receptor sites for chlorhexidine in the oral cavity as related to its observed clinical effect. J Antibiot (Tokyo), 1985 Jun, 38(6), 779 - 86 Laboratory evaluation of a new long-acting 3-azinomethylrifamycin FCE 22250; Della Bruna C et al.; FCE 22250 (3-(N-piperidinomethylazino)methylrifamycin SV) is a member of the new class of 3-azinomethylrifamycins characterized by a long persistance in animals, a good oral absorption and a broad antibacterial spectrum including mycobacteria . In the experimental mice infection sustained by Mycobacterium tuberculosis H37Rv, FCE 22250 shows an efficacy 14 times higher than rifampicin and is still therapeutic when administered once every three weeks. Br Med J (Clin Res Ed), 1985 May 25, 290(6481), 1535 - 8 Which component of sulphasalazine is active in rheumatoid arthritis? Pullar T, Hunter JA, Capell HA. Sulphasalazine is known to be effective as a second line agent in the treatment of rheumatoid arthritis . The two chemical constituents of sulphasalazine (sulphapyridine and 5-aminosalicylic acid) were assessed separately in the treatment of rheumatoid arthritis . Over 24 weeks sulphapyridine showed a pronounced second line effect comparable with sulphasalazine and with a similar toxicity profile, whereas 5-aminosalicylic acid showed only a weak first line effect . Thus sulphapyridine appears to be the active moiety responsible for the second line effect of sulphasalazine in rheumatoid arthritis . The efficacy of the antibacterial component of sulphasalazine yet again permits speculation about the role of a bacterial pathogen in the aetiopathogenesis of rheumatoid disease. J Chromatogr, 1985 May 10, 340, 401 - 79 Drug level monitoring: chromatography of some minor groups of drugs; Schwarz V et al.; Some important facts about the chromatographic separation of a number of selected categories of drugs are summarized . The data refer to the chromatographic method of choice, stationary phase, mobile phase (carrier gas), detection procedure and (where available) method sensitivity . Also, fundamental instrumental parameters, namely injector, column and detector temperature, carrier gas and mobile phase flow-rate and gradient set-up are reported here . In all cases also the source material used for analysis is specified . The data are presented in table form, each table dealing with a particular category of drugs . The following categories of drugs are being dealt with: anthelmintics, antiarteriosclerotics, antibacterials, anticholinergics and cholinergics, anticoagulants, antidiabetics, antiemetics, antimycotics, antihistamines, antimalarials, antiparasitics, antiparkinsonics, antitussives, antiulcer drugs, antiviral compounds, appetite depressants and immunosuppressives. J Chromatogr, 1985 May 3, 339(2), 347 - 57 High-performance liquid chromatographic method for determination of ciprofloxacin in biological fluids; Jehl F et al.; A simple and precise high-performance liquid chromatographic procedure has been developed for the determination in biological fluids of ciprofloxacin, a new, with extended antibacterial spectrum, quinoline carboxylic acid . The work-up procedure involves a chemical extraction step followed by isocratic chromatography on a reversed-phase analytical column, with ultraviolet detection . The detection limit for blood levels is 10 ng/ml . The calibration curve is linear from this detection limit to 10 microgram/ml . The statistical analysis of the correlation made between this assay and an agar diffusion procedure during a pharmacokinetic study suggests the existence of one or more active metabolites which could be mainly excreted in the bile. Radiobiologiia, 1985 May-Jun, 25(3), 309 - 13 {Mechanisms of the synergistic action of ionizing radiation and hydrogen peroxide on the viability of bacteria}; Vasil'eva EI et al.; The combined effect of ionizing radiation and minor concentrations of hydrogen peroxide (0.1-0.01 M) has been studied on bacteria differing in the cell wall structure (Gy+, Gy-), radioresistance, and activity of DNA repair system . The H2O2 concentrations applied, which have a slight antibacterial action, enhance significantly the bactericidal effect of ionizing radiation producing a synergistic effect due to the decreased effectiveness of repair of DNA single-strand breaks. J Antibiot (Tokyo), 1985 May, 38(5), 610 - 21 Synthesis of several new carbapenem antibiotics; Ohtani M et al.; A synthesis of several carbapenem antibiotics including 9-methoxythienamycin is described . The final deprotection of C-3 esters was accomplished by a novel procedure using aluminum trichloride under a very mild condition . The antibacterial activity against Gram-positive and Gram-negative bacteria is shown. J Antibiot (Tokyo), 1985 May, 38(5), 561 - 71 Aridicins, novel glycopeptide antibiotics . II . Isolation and characterization; Sitrin RD et al.; A new antibacterial antibiotic complex, aridicin, was produced by a new genus, Kibdelosporangium aridum (SK&F-AAD-216) . The individual factors, aridicins A, B and C, were isolated from the fermentation broth by an Amberlite XAD-7 resin extraction and purified by preparative reversed phase HPLC . The aridicins were found to be novel members of the glycopeptide class of antibiotics as exemplified by ristocetin and vancomycin, based on chemical and spectroscopic data, their molecular weights as determined by FAB mass spectrometry (1,786, 1,800 and 1,814), the detection of actinoidinic acid in their acid hydrolysates, and detailed TLC and HPLC comparisons with representative members of this class. Antimicrob Agents Chemother, 1985 May, 27(5), 701 - 7 Antibacterial action of colistin (polymyxin E) against Mycobacterium aurum; David HL et al.; Mycobacterium aurum was susceptible to the antibiotic colistin (polymyxin E),which had an MIC of 5 micrograms/ml and an apparent bactericidal effect at concentrations above 50 micrograms/ml . Treatment of actively growing cells with sublethal concentrations of colistin (15 micrograms/ml) resulted in synchronized cell division once the antibiotic was removed . Under conditions of synchronized cell growth, one cycle of DNA replication lasted 120 min and one cycle of cell division lasted about 180 min . Although the antibiotic treatment during synchronization experiments did not produce apparent changes in the bacterial envelope, it was accompanied by the accumulation of a polysaccharide-like substance in the bacterial cytoplasm which gradually decreased after the removal of antibiotic and by an increase in the number of mesosomes at 3 h after antibiotic removal . This step was closely linked to the doubling time of bacteria . Lethal concentrations of colistin of 50 and 100 micrograms/ml, which caused about 90 and 99% cell death, respectively, produced significant cytoplasmic membrane injuries, patchy appearance of the cell wall outer polysaccharide layer, and little cell lysis . These data indicate that the cytoplasmic membrane is a site of action of colistin and raise a question as to whether an outer bilayer exists in mycobacteria, at least functionally. Pathol Biol (Paris), 1985 May, 33(5), 354 - 8 {Serum antibacterial activity during antibiotic treatment in automated bacteriology}; Blin C et al.; The conventional serum-dilution bactericidal test used for monitoring antibiotic therapy in severely infected in patients requires 72 h . Use of an automaton would be expected to provide faster results . We tested the MS-2 diagnostic automaton which performs kinetic analysis of bacterial growth . A relation between exponential growth onset time and initial bacterial concentration of the inoculum was first determined using successive ratio 10 dilutions . Sixty-two serum samples from twenty-one patients with endocarditis or septicemia were examined . A selection of findings is presented . Results of the automatic method and serum-dilution bactericidal test are studied comparatively . From our data we define the major advantages of automation: only 0.65 ml of serum and 10 minutes are needed to perform the test and results are obtained in five to twelve hours according to the bacterial strain . This new technique could be integrated in the monitoring protocol of severe infections. Farmaco {Sci}, 1985 May, 40(5), 359 - 68 Synthesis and antibacterial activity of 3-(2-arylvinylen)-2-isoxazolines; Vittorio F et al.; 3-{2-(5-Nitro-2-furyl)vinylen}-2-isoxazoline (VIII) and 3-nitro-, 3-amino- and 3-acylaminostyryl-2-isoxazolines have been synthesized and tested for antibacterial activity . Compound (VIII) showed potent antibacterial activity in vitro against several strains of S . aureus and E . coli (two to eight times more active than furazolidone) . None of the styryl derivatives exhibited significant activity. J Dent Res, 1985 May, 64(5), 818 - 21 A comparison of the antibacterial and cytotoxic effects of parachlorophenol; Messer HH et al.; The antibacterial and cytotoxic effects of parachlorophenol (as 35% camphorated PCP and 2% aqueous PCP) were compared directly, using the agar overlay technique . Human pulp fibroblasts and L929 cells were grown to confluence in 60-mm petri dishes . Bacterial suspensions (S . aureus, E . coli) in agar were poured as a thin layer in 60-mm petri dishes . All were overlaid with agar . Cells were exposed to medicament via filter paper discs placed on the agar surface . After 24 hours, the zone of cell lysis (fibroblasts) or inhibition of bacterial growth was measured as diameter in mm . A dose-response relationship was observed for both fibroblasts and bacteria . The zone of inhibition for fibroblasts was larger than that for bacteria, indicating that the cytotoxicity of parachlorophenol exceeds its antibacterial activity. Acta Odontol Scand, 1985 May, 43(2), 91 - 5 Bacteriological studies on endodontic paper points; Orstavik D et al.; Four brands of endodontic paper points were subjected to tests for sterility, antibacterial activity, and suitability as vehicles for bacteriological sampling procedures . No brand showed growth in the sterility assay . One brand showed weak but reproducible antibacterial activity . Recovery of viable bacteria after absorption into the points varied and appeared to depend both on the brand of point and on the bacterial strain used . One brand appeared ineffectual for clinical bacteriological sampling procedures. J Nat Prod, 1985 May-Jun, 48(3), 435 - 9 13-Deoxycarminomycin, a new biosynthetic anthracycline; Cassinelli G et al.; A new antitumor antibiotic, 13-deoxycarminomycin, has been isolated from the anthracycline complex produced by Streptomyces peucetius var . carminatus (ATCC 31502), a biochemical mutant of Streptomyces peucetius var . caesius, the doxorubicin-producing microorganism . The new anthracycline, showing antibacterial and cytotoxic activity in vitro, was found active against P-388 murine leukemia. Minerva Med, 1985 Apr 7, 76(14-15), 729 - 32 {Problems of infection in drug addicts and current possibilities of treatment}; Rolloni M et al.; Cefuroxime (a third-generation cephalosporin) administered parenterally (mostly i.m.) at a dose of 2-4 g/day for 4-16 days (mean 9.26 days) displayed marked antibacterial activity and excellent tolerability when employed in the treatment of variously located acute inf