Antimicrobial

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 infections in 120 drug addict out-patients with almost constant pronounced immune depression . The drug is regarded as the antibiotic of choice in the outpatient management of infection episodes in immunodepressed subjects at high risk of infection.

S Afr Med J, 1985 Apr 6, 67(14), 553 - 4
Intractable postphlebitic ulceration of the leg; Garber N; A new regimen for the successful treatment of intractable postphlebitic ulceration of the leg is described . It is based on preliminary culture of organisms in the ulcers followed by sensitivity tests to ascertain the appropriate antibiotics or antibacterials to be used . Patients with Pseudomonas infection are hospitalized and receive: intramuscular injections of amikacin sulphate 500 mg twice daily for 7 days; a once-daily spraying of antibiotic powder on the ulcer for 7 days; and a topical gentian violet regimen once daily for a further 2 days to encourage adhesion of a dressing to the ulcer bed . After discharge the patients are treated in the consulting rooms . Ulcers without Pseudomonas infection but from which organisms have been cultured are treated in the consulting rooms with drugs indicated by the results of sensitivity tests, and topical gentian violet . Patients from whom organisms have not been cultured are treated with co-trimoxazole and topical gentian violet . Patients are taught correct bandaging of the calf with a 150 mm wide crepe bandage and a Rowden Foote elastic bandage . Firm bandaging prevents calf oedema, the factor predisposing to ulceration . Patients are initially seen daily and then, as the dressing becomes adherent, at decreasing intervals until it is shed . Both bandages are worn until the affected tissues heal . The patient is then fitted with a below-knee heavy-duty elastic stocking.

J Antibiot (Tokyo), 1985 Apr, 38(4), 477 - 84
N-Substituted derivatives of 23-amino-4',23-dideoxymycaminosyl tylonolide . Synthesis and antibacterial activity; Sakamoto S et al.; 23-Amino-4',23-dideoxymycaminosyl tylonolide diethyl acetal (5) has been prepared from 4',23-dideoxy-23-iodomycaminosyl tylonolide diethyl acetal (3) by treatment with sodium azide followed by selective reduction of the resulting azide (4) . 23-Acylamino-23-deoxy (6 approximately 8) and 23-deoxy-23-urethane-type compounds (12 approximately 15) were further prepared . Treatment of the 23-alkylamino-4',23-dideoxymycaminosyl tylonolides (9, 10) with chloroformates gave 23-N-alkyl-23-deoxy-23-urethane-type compounds (16 approximately 21, 29, 30) . 23-N-Alkyl-23-deoxy-23-(2-hydroxyethalamino and 2-methoxyethylamino)-4',23-dideoxymycaminosyl tylonolides (22 approximately 25, 27, 28) were prepared from 3 and the corresponding amines . Antibacterial activities and toxicities (for 23 and 27) of these compounds are described . toxicities (for 23 and 27) of these compounds are described.

Chemioterapia, 1985 Apr, 4(2), 170 - 5
Antibacterial activity of fosmidomycin on chromosomic and plasmid-determined fosfomycin-resistant strains; Mendez FJ et al.; The antibacterial activity of fosmidomycin (Fm) on chromosomic and plasmid-determined fosfomycin-resistant (For) strains of Gram-negative bacteria was studied . Presence of For-plasmids did not protect host bacteria from the antibiotic effect of Fm . In clinical isolates Fm was more active than Fo in 67% of the strains whereas Fo was more active for only 2%; 76% of the strains showed cross resistance to both antibiotics . The Fmr character was not transferred by conjugation . For mutants selected in the hospital environment as well as in the laboratory did not always show cross resistance with Fm, and the alterations in the transport systems of both antibiotics were not the only mechanism of cross resistance.

Hautarzt, 1985 Apr, 36(4), 227 - 31
{Eczema of the lower leg and contact allergy}; Lindemayr H et al.; Seventy-three patients suffering from stasis dermatitis with or without leg ulcers (group A) and 565 patients with other eczemas (group B) were patch tested with a series of 37 vehicle constituents and topical preparations . In group A the most common reactions were obtained with wool alcohols (24.7%), eucerin (21.9%), lanette N (17.2%), lanette O (11.0%) lanette E (8.2%), parabens (9.6%), a number of preparations containing these ingredients, and prophylene glycol (9.6%) . In group B there were only positive reactions to lanette E (6.0%, test concentration 20%/vaseline) and sodium lauryl sulfate (5.8% positive, 5%/water), but irritant reactions were suspected in most cases . Additionally, group A patients were patch tested with standard allergens, which most frequently revealed contact allergies to balsam of Peru (19.1%) and mercuric bichloride (6.8%) . Among the local antibacterial agents, the most common allergens were neomycin (32.9%) and bacitracin (12.3%) . The number of patients with stasis dermatitis who reacted to one or more test substances had increased to 71.3%, as compared to the 57% evaluated in a similar study in 1977.

Fundam Appl Toxicol, 1985 Apr, 5(2), 370 - 81
Degeneration of the rat and canine adrenal cortex caused by alpha-(1,4-dioxido-3-methylquinoxalin-2-yl)-N-methylnitrone (DMNM); Yarrington JT et al.; The antibacterial drug alpha-(1,4-dioxido-3-methylquinoxalin-2-yl) N-methylnitrone (DMNM) given at a dose of 22.5 mg/kg bid to four dogs for 14 days caused diminished adrenal cortical reserves as determined by decreased plasma cortisol (three dogs) and lower aldosterone levels (four dogs) following the intravenous infusion of ACTH . A dose of 100 mg/kg/day of DMNM administered to rats for 31 or 35 days resulted in significant decreases in blood glucose . Histologically, the adrenal glands of both species treated with DMNM for a maximum period of 21 days (dogs) and 35 days (rats) had widespread granular and vacuolar degeneration of the cortex . This degeneration in treated rats began in the zona reticularis and inner regions of the zona fasciculata and eventually involved the entire cortex including the zona glomerulosa . As a result of treatment, significant ultrastructural alterations within cells of the rat and canine adrenal cortex consisted of degeneration of the mitochondria and an increase in the numbers and lipolysis of lipid droplets . The ultrastructure of the zona reticularis and fasciculata was most severely affected.

Antibiot Med Biotekhnol, 1985 Apr, 30(4), 261 - 4
{Biological action and complex-forming properties of a macrotetrolide antibiotic complex}; Nefelova MV et al.; Macrotetrolide antibiotic complexes containing 60-80 per cent of nonactin were studied and their high antibacterial activity was shown . The macrotetrolides had a disintegrating effect on the bacterial membrane, which was evident from induction of the protoplast lysis and release of low-molecular compounds from the bacterial cells . The complex-forming properties of nonactin with respect to the ammonium, potassium and sodium ions were investigated in vitro . The selectivity level with respect to the ammonium ions was higher . Nonactin incorporated into an artificial membrane provided a linear dependence of the delta mV on the ammonium chloride concentration within the ranges of 10(-1)-10(-5) M.

Farmaco {Sci}, 1985 Apr, 40(4), 237 - 48
1-Ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1H-pyrrol-1-yl)-quinoline-3-carb oxylic acid, a new fluorinated compounds of oxacin family with high broad-spectrum antibacterial activities; Stefancich G et al.; The synthesis of 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1H-pyrrol-1-yl)quinoline-3-carboxy lic acid, a new fluorinated high broad-spectrum antibacterial agent related to nalidixic acid is described . The title compound has been prepared by the reaction of 4-fluoro-3-(1H-pyrrol-1-yl)aniline with diethyl ethoxymethylenemalonate, cyclization of the malonate obtained to the quinolinecarboxylate ester, ethylation of the ester, followed by hydrolysis with aqueous sodium hydroxide . The new derivative proved very active against both gram-positive and gram-negative bacteria . Its activities in comparison with those of nalidixic acid, pipemidic acid, piromidic acid and enoxacin were found to be greatly superior with regard to the unfluorinated compounds and somewhat superior also to enoxacin . The known 1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(pyrrolidin-1-yl)quinoline-3- carboxylic acid, here prepared by catalytic hydrogenation of the pyrrole moiety of the title compound, has been found to be less active as an antibacterial agent.

J Antibiot (Tokyo), 1985 Apr, 38(4), 460 - 5
Novel antitumor antibiotics, CI-940 (PD 114,720) and PD 114,721 . Taxonomy, fermentation and biological activity; Tunac JB et al.; The novel, broad-spectrum antitumor antibiotics, CI-940 (PD 114,720) and PD 114,721 are components of bioactive compounds produced by a novel actinomycete (ATCC 39366) . The organism is unique in that whole cell analysis revealed LL-diaminopimelic acid and major amounts of arabinose . These new antibiotics exhibit potent antitumor activity in vitro and in vivo versus an array of tumors and possess strong antibacterial and antifungal activity . The above antibiotics are produced in 7,570-liter fermentors at yields of 5 approximately 8 micrograms/ml.

Burns Incl Therm Inj, 1985 Apr, 11(4), 297 - 300
Exposure-Eusol treatment for burn wounds; Shah A; Data from 45 adult patients with flame burns covering up to 20 per cent EAB (Group 1), 21-40 per cent (Group 2), and 41-60 per cent (Group 3) are presented . Each group contains 15 patients with 29 females and 16 males, and females had the more extensive burns . All the patients were treated by the exposure method followed by Eusol dressings beginning between post burn days 5 and 7, i.e . as soon as infection was detected or the eschar had started separating . Eusol is an effective antibacterial agent and also assists in slough separation . It appears to be inactive against living tissues and helps obtain healthy granulation tissue . The bed thus created is ideal for grafting . A burn wound up to 40 per cent EAB is suitable for treatment by the exposure-Eusol method . Septicaemia was the common cause of mortality and its incidence was directly related to the extent of injury.

Int J Clin Pharmacol Ther Toxicol, 1985 Apr, 23(4), 215 - 8
Use of a combination of an anti-inflammatory steroid, an antibacterial agent and an antifungal in dermatological practice; Pellerano S; Forty patients with skin diseases of various origins were treated with a combination of three creams, the respective bases of which were clobetasone butyrate, sodium fusidate and ketoconazole . Satisfactory results were obtained in 97.5% of cases, with remission of symptoms and good healing of lesions . Tolerance was excellent in 97.5% of cases, with only one patient complaining of burning sensations after the applications.

Scand J Dent Res, 1985 Apr, 93(2), 158 - 61
Influence of antiseptic storage solutions on physical properties of endodontic guttapercha points; Moller B et al.; The effect of three commonly used antiseptic storage solutions on some physical properties of endodontic guttapercha points was studied . The solutions tested were: 70% isopropyl alcohol, 5% chloramine and 0.5% chlorhexidine . As a control solution, physiologic saline was used . There was a marked decrease in the force necessary to bend the points after 1 month . With few exceptions, the greatest decrease was seen with solutions containing alcohol, i.e . chlorhexidine and isopropyl alcohol . The difference between aqueous and alcoholic storage solutions was also noted for linear dimensional changes . Physiologic saline and chloramine hardly affected the length of the points . The decrease in stiffness may add to the difficulties when handling guttapercha points of small dimensions in curved root canals . From this point of view it is therefore recommended to avoid storage of points in antibacterial solutions . Rather, an effective surface disinfecting of the points immediately prior to use would be desirable.

Proc Natl Acad Sci U S A, 1985 Apr, 82(8), 2240 - 3
Molecular cloning, cDNA sequencing, and chemical synthesis of cecropin B from Hyalophora cecropia; van Hofsten P et al.; Two cDNA clones containing coding information for cecropin B from the Cecropia moth (Hyalophora cecropia) were identified by means of a synthetic probe . Sequencing of the two inserts showed that cecropin B is processed from a 62-amino acid residue precursor molecule including a 26-residue leader peptide and a COOH-terminal glycine residue . The latter presumably donates the nitrogen of the amide group present on the COOH-terminal leucine residue of the mature cecropin B . The sequence deduced for the mature cecropin B differed in the COOH-terminal region from the tentative structure previously determined by carboxypeptidase digestion . To settle the discrepancy, cecropin B was synthesized according to the cDNA sequence with an amidated COOH-terminal leucine . Natural and synthetic cecropin B were found to be indistinguishable with respect to electrophoretic mobility and antibacterial activity against seven different bacteria . The COOH-terminal tetrapeptides were isolated from both natural and synthetic cecropin B and found to be indistinguishable . The correct sequence for cecropin B is (formula; see text).

Science, 1985 Mar 15, 227(4692), 1296 - 303
Antiviral chemotherapy and chemoprophylaxis; Dolin R; Antiviral compounds have been developed for use in chemoprophylaxis and chemotherapy of a variety of infections in humans, including those caused by influenza viruses, respiratory syncytial virus, and herpesviruses . The efficacy of several of these compounds has been demonstrated in rigorously controlled trials . Advances in molecular virology have led to the identification of biochemically defined, virus-specific functions that serve as appropriate targets for the future development of antiviral compounds . Clinical investigators and practicing physicians are now confronting questions previously raised with the use of antibacterial antibiotics . These questions concern appropriate routes of administration for antiviral compounds, optimal dosage regimens, risks of long-term prophylaxis, and the emergence of resistant organisms.

J Antibiot (Tokyo), 1985 Mar, 38(3), 296 - 301
Isolation of dealanylalahopcin, a new amino acid, and its biological activity; Higashide E et al.; A new amino acid, dealanylalahopcin, was isolated from a culture filtrate of Streptomyces albulus subsp . ochragerus; it was also formed by the enzymatic hydrolysis of alahopcin using microbial alpha-amino acid ester hydrolase . The amino acid was obtained as colorless needles and its molecular formula is C6H10N2O5 . It showed very weak antibacterial activity against Gram-positive and Gram-negative bacteria, and weak inhibitory activity against the collagen prolylhydroxylase.

Ann Thorac Surg, 1985 Mar, 39(3), 277 - 9
Late Mycobacterium chelonei bioprosthetic valve endocarditis: activation of implanted contaminant?
Rumisek JD, Albus RA, Clarke JS.
Mycobacterium chelonei contamination of the Hancock porcine heart valve prosthesis occurred in a few lots manufactured between October, 1975, and August, 1976 . The unimplanted valves were recalled, but a number of valves in their cohort had already been implanted . This report describes a patient with Mycobacterium chelonei endocarditis of a Hancock bioprosthetic heart valve belonging to this cohort that occurred three years after implantation . We are aware of four similar instances of mycobacterial endocarditis and believe that these latent infections originated either from surgical inoculation or from implantation of a contaminated valve prosthesis . Other Hancock valves manufactured between October, 1975, and August, 1976, may harbor latent M . chelonei . We believe early valve replacement with aggressive combination antibacterial and antituberculosis therapy is essential for control of atypical mycobacterial valve endocarditis.

Am Rev Respir Dis, 1985 Mar, 131(3), 348 - 51
In vitro antituberculosis activity of a new antibacterial substance ofloxacin (DL8280); Tsukamura M; A new antituberculosis agent, ofloxacin (DL8280), inhibited the growth of Mycobacterium tuberculosis at concentrations of 0.63 to 1.25 micrograms/ml . There were no cross-resistance relationships between this agent and other antituberculosis agents . The agent delayed the growth rate of M . tuberculosis (strain H37Rv) at concentrations of 0.2 to 0.5 microgram/ml . It showed considerable bactericidal activity at concentrations a little higher than the growth-inhibitory concentration . The combined effect with other antituberculosis agents seemed to be additive . The pattern of resistance that developed with this agent was the obligatory two-step pattern, and there were 2 resistant phenotypes.

J Immunol, 1985 Mar, 134(3), 1930 - 4
Nonphagocytic dendritic cells are effective accessory cells for anti-mycobacterial responses in vitro; Kaye PM et al.; The accessory cell requirements for a given T cell response may be examined in vitro by using highly purified lymph node T cells . We have examined the capacity of different antigen-presenting cells to stimulate proliferation of Mycobacterium tuberculosis-primed T cells when the antigenic challenge is either soluble or particulate in nature . By titrations of cell number and antigen concentration, it was shown that dendritic cells are not only extremely efficient at presenting soluble mycobacterial antigen compared with various macrophage populations, but also that they are capable of presenting whole mycobacteria . Because phagocytosis of mycobacteria does not occur with these cells, we suggest that processing of antigen by dendritic cells may be initiated at the plasma membrane . Because macrophages are not essential for this in vitro response, a role for dendritic cells in antibacterial immunity in vivo is implicated.

Quad Sclavo Diagn, 1985 Mar, 21(1), 78 - 86
{Clinical and experimental research on some toothpastes}; Borea G et al.; Authors assayed in vitro 9 toothpastes (signed A to I) against 8 types of microorganisms . Toothpaste D yielded best results, toothpastes A and B shown no antibacterial power; the other ones had intermediate degrees of effectiveness . Authors also performed an in vivo study testing 3 toothpastes on to 5 healthy volunteers, but results are not statistically significant.

Drugs, 1985 Mar, 29(3), 262 - 79
Current guidelines on the use of antibacterial drugs in patients with malignancies; Mayer KH et al.; Patients with malignant disease may be predisposed to bacterial infections because of neoplastic disruption of normal tissue barriers, exogenous immunosuppressive therapy (drugs with or without radiation), and intrinsic host immune deficits secondary to these diseases . Diminished polymorphonuclear leucocyte numbers or function and impaired humoral immunity are highly correlated with the development of serious bacterial infections . The usual signs and symptoms of infection may be absent or altered in a compromised host . Therapy must be instituted promptly upon clinical suspicion of bacterial infection, and empirical choices should usually include combinations that are synergistic for likely pathogens based on knowledge of the local predominant flora and susceptibility data . Synergism has most often been demonstrated in combinations that utilise a beta-lactam (semisynthetic penicillin or cephalosporin) and an aminoglycoside . Triple drug therapy has not been shown to be advantageous . Monotherapy with third generation cephalosporins, carbapenems, monobactams, or ureidopenicillins has not been proven to offer advantages over 2-drug regimens for these patients . Granulocytopenic patients who respond to 2-drug therapy but remain neutropenic may need continued treatment until the neutropenia subsides . Those who do not respond and remain febrile with an unclear focus may need to be started on antifungal therapy in addition to the antibacterial agent . The use of oral agents for the prophylaxis of neutropenic patients against bacteraemia remains controversial . If drugs are used, co-trimoxazole and nystatin suspension may be preferable.

J Hosp Infect, 1985 Mar, 6 Suppl A, 67 - 71
Efficacy of povidone-iodine in pre-operative skin preparation; Georgiade G et al.; Cultures were obtained of the microbial flora from the skin of the operation site pre-operatively and following preparation of the surgical field with povidone-iodine (PVP-I) . Preliminary results indicate that PVP-I is a reasonable and effective antibacterial agent when used to prepare skin for surgical operations.

J Hosp Infect, 1985 Mar, 6(1), 20 - 30
The antibacterial properties of sodium hypochlorite and sodium dichloroisocyanurate as hospital disinfectants; Bloomfield SF et al.; The antibacterial activity of unbuffered sodium dichloroisocyanurate (NaDCC) (pH 6.6) and of sodium hypochlorite (NaOCl) buffered to pH 7.2, 9.0 and 10.6 was compared . Under clean conditions, solutions of NaDCC at pH 6.6 or NaOCl at pH 7.2 and 9.0 with 100-200 mg l-1 available chlorine showed satisfactory disinfectant activity against vegetative bacteria . Sporicidal action required higher concentrations of both agents, and NaOCl at pH 7.2 showed most activity . In the presence of organic matter NaDCC offers significant advantages over NaOCl, a 3000 mg l-1 solution of NaDCC giving satisfactory activity in the presence of plasma concentrations up to 20% v/v compared with NaOCl solutions at pH 7.2, 9.0 and 10.6 which were inactivated at chlorine concentrations up to 5000 mg l-1 . Although NaOCl pH 10.6 showed satisfactory disinfectant activity under clean conditions, our results indicate that formulations at this pH should not be used where sporicidal action is required or where substantial organic soiling is anticipated.

S Afr Med J, 1985 Feb 16, 67(7), 257 - 8
The antibacterial action of honey . An in vitro study; Jeddar A et al.; The reported antibacterial effect of pure honey was evaluated by an in vitro study testing the growth of various Gram-positive and Gram-negative bacteria in media containing varying concentrations of honey . It was found that most pathogenic bacteria failed to grow in honey at a concentration of 40% and above . The possible mechanisms of this effect are briefly outlined.

Lab Anim Sci, 1985 Feb, 35(1), 71 - 5
Absence of therapeutic blood concentrations of tetracycline in rats after administration in drinking water; Porter WP et al.; Because of ease of administration and broad antibacterial spectrum, tetracycline often is administered in drinking water to control infectious diseases of rats . Assay of serum after a gavage bolus of tetracycline (300 mg/kg body weight) revealed little absorption of tetracycline by this route . Rats were given water containing tetracycline at several concentrations (400 mg/liter, 4g/liter, and 4 g tetracycline plus 50 g sucrose/liter) ad libitum and serum concentrations of tetracycline were monitored . Bioassay of serum samples from these animals, taken during 72 hours of water medication, revealed no detectable tetracycline concentrations (greater than 0.2 mcg/ml) in the 400 mg and 4 g/liter groups . Two of eighteen serum samples from the group given 4 g tetracycline with 50 g sucrose/liter had minimal therapeutic tetracycline concentrations (0.3 mcg/ml) effective for Mycoplasma pulmonis . Some of the animals given tetracycline ad libitum in drinking water drank very little and lost weight compared to control animals . These findings indicate that the practice of adding tetracycline to drinking water of rats may be ineffective in controlling systemic diseases, and also be detrimental to the treated animals.

Jpn J Antibiot, 1985 Feb, 38(2), 431 - 40
{Laboratory and clinical studies of BRL 25000 (clavulanic acid-amoxicillin) granules in the pediatric field}; Nishimura T et al.; The authors have carried out laboratory and clinical studies on the BRL 25000 granule (containing 2 parts amoxicillin and 1 part clavulanic acid) . The antibacterial activity of BRL 25000 against 29 clinically isolated strains of S . aureus, 30 E . coli and 30 K . pneumoniae were measured by the agar dilution method using an inoculum size of 10(6) cells/ml . beta-Lactamase production was detected by the Nitrocefin method . The MICs of BRL 25000 against S . aureus ranged from 0.2 approximately 12.5 micrograms/ml, with the majority of strains being inhibited by 1.56 micrograms/ml or less . Seven beta-lactamase producing strains of S . aureus were all inhibited by less than 12.5 micrograms/ml . The range against E . coli was 1.56 approximately 100 micrograms/ml, with the majority inhibited by 6.25 micrograms/ml or less . Fifteen beta-lactamase producing strains of E . coli were inhibited by 6.25 approximately 100 micrograms/ml and the majority by 25 micrograms/ml or less . All strains of K . pneumoniae were beta-lactamase producers and the MIC distribution against K . pneumoniae was 1.56 approximately 50 micrograms/ml, with a majority inhibited by 3.13 micrograms/ml or less, 96% of strains, were inhibited by less than 6.25 micrograms/ml . Against K . pneumoniae, BRL 25000 showed a 8 to 16-fold superiority when compared with AMPC . In a pharmacokinetic study, BRL 25000 granules were orally administered to children in the fasting state at single doses of 7.5 mg/kg and 20 mg/kg . The peak serum levels of AMPC were 6.13 and 6.94 micrograms/ml approximately 1 hour after administration and decreased with half-lives of 1.08 and 0.97 hours, respectively . The corresponding serum levels of CVA were 1.16 and 1.90 micrograms/ml at 1 hour after administration, with half-lives of 0.99 and 0.87 hour, respectively . In clinical studies, the BRL 25000 granule was effective in 39 cases of bacterial infection out of a total of 41 treated . Side effects were limited to 2 cases of diarrhea and minor changes in laboratory findings were elevation of serum GOT (1 case), elevation of serum GPT (1 case), and eosinophilia (2 cases).

J Antibiot (Tokyo), 1985 Feb, 38(2), 186 - 96
Chemical modification of spiramycins . V . Synthesis and antibacterial activity of 3'- or 4''-de-N-methylspiramycin I and their N-substituted derivatives; Sano H et al.; The 3'- and 4''-de-N-methylspiramycins were synthesized selectively, and then were converted to various N-substituted derivatives . 4''-De-N-methyl derivatives were more active than 3'-de-N-methyl ones . Among the derivatives, 4''-N-Fmoc-glycyl and 4''-N-benzyl-4''-de-N-methylspiramycin I were the most active in vitro, and were comparable to spiramycin I . 4''-De-N-methylspiramycin I was about half as active as spiramycin I in vivo.

Infect Immun, 1985 Feb, 47(2), 457 - 64
Lysozyme-mediated aggregation and lysis of the periodontal microorganism Capnocytophaga gingivalis 2010; Iacono VJ et al.; The ability of lysozyme to aggregate and lyse the gram-negative capnophilic periodontal microorganism Capnocytophaga gingivalis 2010 was monitored optically at 540 nm . Both hen egg white and chromatographically purified human lysozymes had significant but similar aggregation potentials for both logarithmic- and stationary-phase bacteria . In general, an increase in enzyme concentration resulted in a graded increase in both the initial and maximum changes in turbidity which occurred during the reaction period . The greatest change in turbidity occurred within the initial minutes of interaction of lysozyme and the cells, and the extent of aggregation paralleled a rapid depletion of lysozyme by the suspensions during the first minute of its incubation with the bacteria . Interestingly, the muramidase inhibitors N-acetyl-D-glucosamine and histamine did not block aggregation, whereas maleylation of lysozyme completely inhibited its aggregating ability . Demaleylation, however, restored aggregation activity comparable to the native enzyme, indicating that maleylated lysozyme retained its integrity and that aggregation was primarily dependent on charge . The addition of up to physiological concentrations of NaHCO3 and NaCl to cell aggregates resulted in varying degrees of deaggregation and lysis . Surprisingly, ultrastructural analysis of lysozyme-treated cells revealed morphological changes with or without the addition of salt . Damage appeared to occur at the blunted polar end of the cells where there was a large spherical outpouching bordered by a damaged cell envelope . Damaged cells uniformly contained dense granular cytoplasmic debris . In effect, the cationic enzyme lysed C . gingivalis 2010, which was not apparent in the spectrophotometric assay . The paradoxical finding that during bacterial aggregation there was lysis may be of significance to the further elucidation of lysozyme's antibacterial role in the gingival sulcus.

Arthritis Rheum, 1985 Feb, 28(2), 198 - 203
Arthroscopy in septic arthritis . Lidocaine- and iodine-containing contrast media are bacteriostatic; Dory MA et al.; Puncture of septic foci is usually performed to determine the responsible bacteria . If contrast medium is used instead of saline to rinse the lesion and to withdraw an adequate bacteriologic specimen, the opacification provides valuable information about the extent of the changes . Since lidocaine is usually used as a local anesthetic when patients undergo this procedure, we tested the in vitro antibacterial effects of lidocaine 1%, as well as those of 2 contrast media--meglumine amidotrizoate and metrizamide--on several bacteria . In particular, we looked at the influence of the concentration of inoculum used and the duration of contact before culture . The contrast media did not significantly affect bacterial growth when contact before culture did not exceed 3 hours . In contrast, lidocaine had a significant antibacterial effect, indicating that it should not enter into contact with the bacteriologic specimen.

Jpn J Antibiot, 1985 Feb, 38(2), 507 - 37
{Clinical trials of BRL 25000 (clavulanic acid-amoxicillin) granules on skin and soft tissue infections in the field of pediatrics}; Motohiro T et al.; BRL 25000 is a combination of a newly-developed beta-lactamase inhibitor clavulanic acid (CVA) and amoxicillin (AMPC) in the ratio of 1 to 2 . The drug, as medium granules, was administered to a total of 92 pediatric patients, ranging in age from 1 month to 13 years and 2 months, with cutaneous/soft tissue infections (70 impetigo, 6 furuncle, 7 phlegmon, 6 abscess and 3 cases of lymphadenitis) . It was found subsequently that 2 of the 70 impetigo cases had received topical antibiotic medication and these were excluded from clinical evaluation to give a total of 90 evaluable cases . The daily dosage of BRL 25000 ranged from 23.7 to 75.0 mg/kg, given in 3 or 4 divided doses (average 48.5 mg/kg) and the duration of treatment was for 3 to 13 days (average 6 days) . Clinical isolates of S . aureus from the above cases were examined for beta-lactamase production and their susceptibility determined to the 5 antibiotics BRL 25000, AMPC, CVA, cephalexin (CEX) and cefaclor (CCL) . The drugs' clinical effects on the various diseases, bacteriological effects and side effects were also studied . At an inoculum of 10(8) cells/ml, major MICs of BRL 25000, AMPC, CVA, CEX and CCL against 71 strains of S . aureus, including beta-lactamase negative ones, were 3.13 mcg/ml, 12.5 mcg/ml, 50 mcg/ml, 12.5 mcg/ml and 12.5 mcg/ml, accounting for 60.6, 38.0, 49.3, 38.0 and 43.7% of the strains respectively, whilst at an inoculum of 10(6) cells/ml, major MICs were 1.56 mcg/ml, 3.13 mcg/ml, 25 mcg/ml, 6.25 mcg/ml and 3.13 mcg/ml, accounting for 57.7, 33.8, 83.1, 50.7 and 54.9%, respectively . It was noted that all drugs tended to show smaller MIC values as the inoculum size was reduced to 10(6) cells/ml and that BRL 25000 showed the most potent antibacterial activity of all 5 drugs.(ABSTRACT TRUNCATED AT 400 WORDS)

Clin Otolaryngol, 1985 Feb, 10(1), 31 - 41
Fashion, science and technical change: the history of the treatment of glue ear; Black NA; One reason for the current epidemic in the rate of surgery for glue ear in children is that a shift in treatment has taken place from non-surgical to surgical methods . An historical review of the treatment of this condition reveals the existence of previous 'surgical epidemics' and the importance of two particular factors-technical developments, such as the design of tympanostomy tubes and the introduction of antibacterial drugs; and the lure of panaceas such as ionizing radiation . In addition, it reveals how medical practice is, like most human behaviour, subject to fashion . Despite this, there is a constant desire by practitioners to be adjudged 'scientific' in their work, and definitions of science are equally susceptible to change over time.

J Antibiot (Tokyo), 1985 Feb, 38(2), 208 - 19
Spectinomycin modification . III . Spectinomycin analogs with C-3'-branched chain sugars; Thomas RC et al.; A variety of C-3'-branched chain analogs of spectinomycin has been synthesized via the intermediacy of spectinomycin derived diazoketones . In vitro antibacterial assay of these compounds has underscored the importance of hydrogen bonding functional groups in this region of the molecule . The most potent of these analogs had activity greater than or equal to the parent.

Schweiz Med Wochenschr, 1985 Jan 19, 115(3), 75 - 86
Mechanisms of bacterial superinfections in viral pneumonias; Jakab GJ; Although it was once thought that bacterial infection was merely a function of the virulence of the microbe it is now known that other pathogens can alter host resistance . With respect to bacterial superinfection during viral pneumonias, three important factors must be considered; the role of the virus, the role of the bacterium, and the immune status of the host . The fact that no one bacterial species is responsible for all human cases of postinfluenzal bacterial pneumonia indicates that there is a general impairment of pulmonary antibacterial defenses brought about by the viral infection . The fact that the rate of intrapulmonary killing varies with different bacterial species indicates that the superinfecting organism can itself play a role in the dual disease process . Finally, it has been amply demonstrated that the resistance of the host is dependent on a variety of factors which include innate variables such as genetic endowment and a multitude of imponderable variables acquired through life experiences which can be considered under the general category of "host factors" . All three factors interact and collectively impinge upon the resistance of the host . Lastly, as influenza virus infections occur most frequently in epidemic outbreaks, the relationship between influenza virus and secondary bacterial infections is the classic example . However, there is growing evidence that an association exists between other virus groups and bacterial pathogens in respiratory tract infections . Adenovirus, parainfluenza virus, and rhinovirus are among the agents that appear to pave the way for bacterial pneumonias . Mycoplasma pneumoniae, once considered to be a virus and the cause of primary atypical pneumonia, may also render the respiratory tract susceptible to bacterial invasion.

J Chromatogr, 1985 Jan 18, 318(2), 299 - 306
Studies on residual antibacterials in foods . III . High-performance liquid chromatographic determination of penicillin G in animal tissues using an on-line pre-column concentration and purification system; Terada H et al.; A simple and reproducible method for the determination of residual penicillin G in edible animal tissues by high-performance liquid chromatography (HPLC) is described . The method consists in an off-line clean-up step using a basic aluminium oxide column and a Sep-Pak C18 cartridge and an on-line pre-column concentration and purification system . The procedure shows good sensitivity and precision . The recoveries from cattle liver, kidney and muscle fortified with 1 microgram/g of sodium penicillin G were 75.0-92.6% and the relative standard deviations were 2.35-4.06% . The detection limit corresponded to 0.05 micrograms/g of sodium penicillin G in animal tissues.

Arch Immunol Ther Exp (Warsz), 1985, 33(2), 331 - 8
Biological properties of dipyridyl sulphides and related compounds; Boduszek B et al.; Antibacterial, antifungal and antitumor activity of 15 newly synthetized compounds were investigated in vitro . These compounds were mainly 1-{4-pyridyl}-pyridinium salts, dipyridyl sulphides and corresponding sulphones . Antitumor activity was evaluated in a model of leukemia L1210, P388, Sarcoma 180, Ehrlich carcinoma, NK-lymphoma and melanoma B16 . None of the compounds investigated, even at the concentration of 100 micrograms/ml, appeared to influence Gram-negative bacteria . However, at the concentration as low as 1.0 microgram/ml, three of them (No . III, VI and VII) strongly inhibited the growth of Gram positive bacteria and fungi . The compounds did not prolong the survival time of Sarcoma 880 leukemia L1210 or P388--bearing mice . Few of the compounds examined exerted marked antitumor effect on Ehrlich carcinoma and NK-lymphoma--compounds No . I and XV inhibited the growth of these tumors by ca . 70% . The strongest inhibitory effect on melanoma B16 was observed with compound No . XV, the effect being dose-dependent.

Pharmatherapeutica, 1985, 4(2), 88 - 91
Therapeutic usefulness of a corticosteroid, antibacterial and antifungal combination in skin diseases of various origins; Marras F; Forty-one patients with skin diseases of various origins were treated with an extempore combination of three creams containing clobetasone butyrate, sodium fusidate and ketoconazole . A mixture of the creams was applied once to 3-times daily for periods ranging from 5 to 15 days (mean 8.5 days) . Assessments were made before, during and at the end of the treatment period using a symptom severity rating scale . The results showed that all symptoms regressed to a significant extent and by the end of the treatment period there had been complete disappearance or improvement with satisfactory remission in 97.6% of the patients . Local tolerance was excellent or good in all patients and there were no reports of any side-effects.

Pharmatherapeutica, 1985, 4(2), 122 - 5
Therapeutic effects and tolerance of an extempore combination of an antibacterial, an anti-inflammatory, and an antimycotic cream in skin diseases of various origins; Pazzaglia A; Forty out-patients suffering from a variety of skin diseases were treated over a period of 7 to 14 days (mean 9.6 days) with twice-daily applications of an extempore combination of sodium fusidate, clobetasone butyrate and ketoconazole creams . The severity of symptoms was assessed before, after 5 days and at the end of treatment and an overall evaluation made of response to therapy . The findings indicated that there was clinical cure or significant improvement in 37 (92.5%) of the patients, with excellent tolerance and no reports of any adverse reactions.

Ter Arkh, 1985, 57(7), 114 - 6
{DNA repair system in nonspecific lung diseases}; Sil'vestrov VP et al.; It has been found that in 35-40% of patients with acute and chronic pneumonia, the reduced ability of peripheral blood lymphocytes for DNA repair is encountered 14 times as frequently as in normal subjects . After discontinuation of antibacterial therapy with penicillin or tetracycline antibiotics marked inhibition of the ability of lymphocytes for DNA repair is recorded . The tendency toward normalization of this characteristic occurs 1 week after discontinuation of antibiotic therapy for acute and 3 weeks for chronic pneumonia . The disorders of the ability of peripheral blood lymphocytes for DNA repair in the conditions under study are regarded as a possible cause of secondary immunodeficiency.

Cancer Invest, 1985, 3(4), 361 - 6
Intravenous usage of gammaglobulin: humoral immunodeficiency, immune thrombocytopenic purpura, and newer indications; Bussel JB et al.; Intravenous gammaglobulin is effective therapy of ITP and other autoantibody-mediated immune cytopenias . All children as well as adults unresponsive to splenectomy or with known immune deficiency are probably the best candidates for treatment with IVGG . Its major advantage, in addition to its efficacy of treatment and possible remission-inducing effect, is that it has the fewest side effects of any treatment of ITP so that it is the best maintenance therapy of patients when effective . Future uses of IVGG remain to be determined . Premature infants with a high mortality from sepsis and with hypogammaglobulinemia due to termination of pregnancy prior to transplacental antibody transfer may benefit from IVGG . A preliminary study suggested such benefit and also showed safety of IVGG treatment in that there was no impaired immune responsiveness of these prematures at 2 years of age (28) . Another potential usage of IVGG involves the treatment of the hypogammaglobulinemia associated with certain types of malignancy . Patients with CLL, especially in the advanced stages, are often hypogammaglobulinemic . Multiple myeloma and Waldenstrom's macroglobulinemia are two other B-cell malignancies associated with antibody production defects which might benefit from antibody replacement therapy . Therapeutic IgG levels may be harder to obtain due to hypercatabolism of immunoglobulin . The issue of immune hyporesponsiveness during intensive chemotherapy is also unexplored . Secondary antibody responses do not seem to be impaired, but primary responses, as tested in numerous immunization studies, are decidedly impaired . Certain protocols, especially those treating high-risk acute leukemias and neuroblastoma during induction therapy are intensive with high rates of sepsis, and may warrant trials of prophylactic IVGG . Similarly, some form of humoral prophylaxis is becoming an important part of the handling of the patient undergoing bone marrow transplantation not only to prevent bacterial sepsis but also to prevent cytomegalovirus (CMV) interstitial pneumonitis . A likely additional usage is gammaglobulin replacement for patients undergoing plasmapheresis, especially if performed multiple times . Finally, the broad spectrum of antibacterial and antiviral antibodies present in the preparations (such as anti-CMV, anti-Group B strep, and antiendotoxin) and the ease and safety of delivery allow the preparations to be used in situations where a hyperimmune preparation might be desired and/or where more than one pathogen is possible . In summary, IVGG is a treatment capable of safely conferring significant benefits to selected patients.(ABSTRACT TRUNCATED AT 400 WORDS)

J Nat Prod, 1985 Jan-Feb, 48(1), 10 - 6
Antibacterial sesquiterpene aryl esters from Armillaria mellea; Donnelly DM et al.; Investigation of the mycelial extract of Armillaria mellea led to the isolation of the known melleolide (2a) and two new sesquiterpene aryl eters, 4-O-methylmelleolide (2b) and judeol (1c) . Their structures were deduced from spectral data and that of (2b) confirmed by X-ray analysis . The new esters (1c) and (2b) showed strong antibacterial activity against gram-positive bacteria.

Ter Arkh, 1985, 57(3), 133 - 5
{2-stage treatment of acute pneumonia patients with rehabilitation at the sanatorial stage}; Shteingardt IuN et al.; A total of 73 patients with acute pneumonia received two-stage treatment: etiotropic treatment based on early etiological diagnosis (at hospital) and subsequent early rehabilitation at sanatorium with the use of peloid therapy . It made it possible to attain the best short-term results in the treatment of pneumonias (as compared with control group patients), to shorten 2-4-fold the times of the patients' stay at hospital and to raise bed capacity, to reduce the total doses and duration of antibacterial therapy, to decrease the possibility of the allergic reactions and side effects, and to reduce 2-fold the cost of antibacterial therapy.

Dev Comp Immunol, 1985 Winter, 9(1), 1 - 10
Lectins and lectin-like molecules in lower plants . I . Marine algae (review); Ingram GA; Marine algae possess agglutinins, generally of unknown carbohydrate specificity, against a diverse array of erythrocytes but in a small number of species these haemagglutinins react with certain human blood group types . In seaweeds, lectins or lectin-like molecules are involved in gamete recognition and consequent reproductive cell fusion . Although some substances produced by algae are antiviral, antifungal, antibacterial, haemolytic and toxic, no similarity to mammalian immunoglobulins either structurally or physico-chemically has been observed for algal agglutinins . Whether such compounds have a defence or immune function and perform an antibody-like role to enable algal species to survive and counteract infections within their environment remains tentative.

Vestn Khir Im I I Grek, 1985 Jan, 134(1), 68 - 70
{Administration of medications via a lymphatic vessel in the treatment of diffuse peritonitis and sepsis}; Pristaiko IaI; Endolymphatic infusions of an antibacterial complex (antibiotic--lysozyme--proteinase inhibitor) resulted in recovery of 92,6% of patients after a complex treatment of diffuse peritonitis and sepsis . Gauze-sorbent tampons used in empyema of pleura give rapid cleaning of the cavity walls from pyo-necrotic masses and decreased the activity of the inflammatory process.

Chemotherapy, 1985, 31(2), 85 - 94
Pharmacokinetics of ceftriaxone and its relation to concentrations in extravascular compartments . Comparison with cefotaxime; Regamey C; Two of the 3rd generation cephalosporins, ceftriaxone and cefotaxime, have an almost identical antibacterial spectrum, but completely different pharmacokinetics . After an intravenous dose of 1 g, peak levels of both cephalosporins were greater than or equal to 100 micrograms/ml . Cefotaxime levels fall rapidly with a T 1/2 of 1.1 h, whereas ceftriaxone persists for 24 h with an unique T 1/2 of 8 h . Cefotaxime is eliminated by the kidneys and metabolized to desacetyl-cefotaxime resulting in a high total clearance . In contrast, ceftriaxone is not metabolized and highly protein bound with a total clearance of only 14 ml/min . Peak concentrations of antibiotics are lower in extravascular compartments than in serum . They depend on the dose administered and the serum T 1/2; they are lower with highly bound drugs . Concentrations of ceftriaxone and cefotaxime were measured by Andrews and Wise in blister fluids, in ascites and pleural fluid by us . We found concentrations of 20-26 micrograms/ml ceftriaxone up to 12 h in ascites, but only 7-15 micrograms/ml cefotaxime . The levels persisted for 24 h for ceftriaxone, whereas they fell rapidly for cefotaxime . Because the minimum inhibition concentrations increase in the presence of proteins, and because free, unbound, microbiologically active ceftriaxone is lower than the measured total antibiotic concentrations, we suggest that 2-gram doses should be administered--at least at the beginning of the treatment of an infectious disease--and for prophylaxis.

J Antimicrob Chemother, 1985 Jan, 15 Suppl A, 273 - 82
Correlation of antibacterial activities of antibiotics in vitro and in animal models of infection; Zak O et al.; Laboratory tests of antibiotic activity in vitro, ranging from simple MIC determinations to sophisticated, computerized models for studying the effects of simulated plasma concentration-time curves of antibiotics in broth, differ inherently from tests in vivo in both the general and specific variables . There are therefore likely to be discrepancies between the results obtained . Apart from the obvious lack of host-defence mechanisms in the in-vitro tests systems, the reasons for these discrepancies have still not been fully elucidated . For the time being, it seems unrealistic to expect that in-vitro tests could be developed that would make it possible to predict the efficacy of any antibiotic against any specific infection in vivo.

J Antimicrob Chemother, 1985 Jan, 15 Suppl A, 131 - 7
Two compartment kinetic model with multiple artificial capillary units; Blaser J et al.; A two compartment in-vitro model was designed to simulate human pharmacokinetics and to expose bacterial cultures to changing drug concentrations, thereby avoiding limitations of conventional antibiotic testing at constant drug levels . Serially placed bacterial compartments, representing extravascular infection sites, interface with a central compartment through artificial capillaries . Drug concentrations within the culture chambers closely mimic interstitial concentrations in vivo . Simultaneous first order elimination kinetics of two drugs with different half-lives were simulated to study antibacterial effects of drug combinations . This in-vitro model is an efficient tool for optimal dosage regimen design and the study of synergistic/antagonistic effects of antibiotic combinations.

J Antimicrob Chemother, 1985 Jan, 15 Suppl A, 117 - 20
Possible approaches to the simulation of antibiotic kinetics and the determination of antibacterial activity in vitro; Tosch W et al.; Various methods of determining antibacterial effects in vitro by simulation of antibiotic kinetics were investigated . MICs were determined in fluids with and without proteins . Only concentrations of free drug were antibacterially active, and these concentrations should therefore be simulated in culture media without protein . Varying drug concentrations can easily be simulated in our in-vitro system, but the question remains which of the concentrations found in the different body fluids is the most representative . Cephalosporins were more active when phagocytosis was simulated, as shown by the continuous elimination of approximately 90% of the bacteria . If phagocytosis was not simulated, the effects of long-lasting concentrations were not decreased as much as those of concentrations corresponding to short half-lives and repeated doses.

Farmakol Toksikol, 1985 Jan-Feb, 48(1), 80 - 2
{Circadian fluctuations in dioxidine toxicity}; Gus'kova TA et al.; It has been established in rat experiments that toxicity of the antibacterial drug dioxydin (1,4-di-N-oxide 2,3-dioxymethylquinoxaline) depends on the time of administration . The drug exhibits the minimal and maximal toxicity upon administration at 8 o'clock p.m . and at 12 o'clock, respectively.

Farmakol Toksikol, 1985 Jan-Feb, 48(1), 77 - 80
{Carcinogenic activity of dioxidine}; Shashkina LF et al.; A study was made of the blastomogenic activity of dioxydin, a new antibacterial broad-action drug . Administration of dioxydin in doses of 20-100 mg/kg (exceeding 2-10-fold the therapeutic dose for humans) to mice and rats intragastrically for 18 months and intraperitoneally (2 years of observation) as well as combined administration of the drug to rats transplacentally and postnatally (1.5 years of observation) did not induce any neoplasms.

Farmakol Toksikol, 1985 Jan-Feb, 48(1), 69 - 73
{Dependence of the embryotoxic action of dioxidine and cyclophosphamide on the immunoreactivity of the maternal-fetal system in mice}; Torchinskii AM et al.; It has been shown that the embryotoxic action of cyclophosphamide and dioxydin (an antibacterial drug) was more pronounced upon syngeneic than upon reciprocal crossing of CBA and C57BL/6 mice . Preliminary (21 days before crossing intrauterine sensitization of C57BL/6 mice with syngeneic or allogeneic lymphocytes obtained from males' spleen led to the attenuation of the embryotoxic action of cyclophosphamide and dioxydin . During sensitization with allogeneic lymphocytes, the embryotoxic action was attenuated more appreciably . Extirpation of the paraaortal lymph nodes in female C57BL/6 mice performed 14-15 days before crossing potentiated the embryotoxic action of cyclophosphamide in the case of allogeneic crossing of females . Upon syngeneic crossing of females with the extirpated paraaortal lymph nodes the intensity of the embryotoxic action of cyclophosphamide remained unchanged . It is concluded that the immune status of the mother-embryo system can, under the definite conditions, determine the intensity of the embryotoxic action of xenobiotics on the mammals.

Mol Pharmacol, 1985 Jan, 27(1), 103 - 8
A study of structure-activity relationships in 4-deoxypyrido{1',2'-1,2}imidazo{5,4-c}rifamycin SV derivatives by electron spectroscopy for chemical analysis and 1H NMR; Cellai L et al.; A new class of rifamycins, 4-deoxypyrido{1',2'-1,2}imidazo{5,4-c}rifamycin SV derivatives, has been synthesized . They are potent antibacterial agents and are not absorbed at the gastrointestinal level and can therefore probably be used as antibacterial intestinal disinfectants . From the present X-ray, electron spectroscopy for chemical analysis, and 1H NMR study, it appears that this peculiar pharmacokinetic behavior is mainly to be attributed to the fact that the pyridoimidazo system exists in these compounds in a mesomeric betaine form, bearing one positively and one negatively charged nitrogen . If it is assumed that rifamycins are generally absorbed by passive diffusion, the presence of the two oppositely charged nitrogens, together with the presence of the phenolic hydroxyls, means that these molecules are ionized at all pH values encountered along the gastrointestinal tract, which thus prevents their absorption . These molecules also display a strong tendency to self-associate both in solution and in the solid state, and the increase in molecular size may also play a role in preventing their absorption.

Antibiot Chemother, 1985, 36, 111 - 33
An evaluation of antipseudomonal antimicrobic agents; Gilbert DN; The data summarized above indicate that major strides have been made in the use of beta-lactam antibiotics for serious infections due to P . aeruginosa . Emergence of resistance during therapy is a worrisome feature of the antipseudomonal beta-lactams . It is also disturbing that in no animal model of infection has beta-lactam monotherapy been superior to aminoglycoside monotherapy or the combination of an aminoglycoside with an antipseudomonal penicillin . Imipenem, used alone, has equalled aminoglycoside antibacterial activity in some experimental settings and may be an exception . In most hospitals, aminoglycoside resistance occurs at a low and predictable incidence . Aminoglycoside nephrotoxicity is infrequent, mild in severity, and reversible . The quinolone family appears promising but clinical studies are pending . Based on the available data, it appears that the standard therapy of serious life-threatening infection due to P . aeruginosa remains the combination of an aminoglycoside and an antipseudomonal penicillin.

Antimicrob Agents Chemother, 1985 Jan, 27(1), 11 - 5
Determination of in vitro susceptibility of Mycobacterium tuberculosis to cephalosporins by radiometric and conventional methods; Heifets LB et al.; Among eight cephalosporins and cephamycins tested in preliminary in vitro screening against Mycobacterium tuberculosis, the most promising for further study was found to be ceforanide, followed by ceftizoxime, cephapirin, and cefotaxime . Moxalactam, cefoxitin, cefamandole, and cephalothin were found to be not active enough against M . tuberculosis to be considered for further in vitro studies . The antibacterial activity of various ceforanide concentrations was investigated by three methods: (i) the dynamics of radiometric readings (growth index) in 7H12 broth; (ii) the number of CFU in the same medium; and (iii) the proportion method on 7H11 agar plates . There was a good correlation among the results obtained with these methods . The MIC for most strains ranged from 6.0 to 25.0 micrograms/ml . The BACTEC radiometric method is a reliable, rapid, and convenient method for preliminary screening and determination of the level of antibacterial activity of drugs not commonly used against M . tuberculosis.

Drugs Exp Clin Res, 1985, 11(1), 49 - 54
Study on the antibacterial activity of ceftazidime in an in vitro pharmacokinetic model; Xerri L et al.; A kinetic model was used to evaluate the activity of ceftazidime against recently isolated bacterial strains . The microorganisms were subjected in vitro to drug concentrations simulating the serum kinetics of ceftazidime after i.v . administration of 1 g of the drug . In these conditions ceftazidime showed a bactericidal effect lasting up to 12 h, even at concentrations below the MICs for some strains . In no case did resistant populations develop after exposure to the drug.

Pharmatherapeutica, 1985, 4(6), 351 - 5
Peri-operative infection prophylaxis with ornidazole and gentamicin in elective colonic surgery; Wenzel M et al.; In a study of 60 patients undergoing elective colonic surgery peri-operative infection prophylaxis by the "one-shot' method was compared with that of 48-hour duration . The antibacterial agents used were ornidazole and gentamicin . Considering the patient population as a whole, no significant differences were found in the results . All the infectious complications which occurred post-operatively were due to bacterial contamination by aerobic pathogens . No anaerobic pathogens were detected in any of the cases.

Microbios, 1985, 43(173), 107 - 14
Heterogeneity in the sizes of proteins which diffuse across the outer membrane barrier of bacteria; Barber C; Proteins of both small and large molecular sizes diffuse together across the outer membrane barrier of bacterial cells . Once outside, the proteins present in convenient extracts react in agar-gel diffusions against correspondingly antibacterial induced antibodies by precipitation lines that occur at various distances from the wells containing the antigens . The distances between the precipitation lines depend on the velocity with which the proteins are moving in the agar gel; their speed is a result of the molecular sizes of the proteins . The differences involve the intrinsic qualities of the species that synthesize the antigens.

Dev Comp Immunol, 1985 Summer, 9(3), 559 - 68
Soluble peptidoglycan fragments stimulate antibacterial protein synthesis by fat body from larvae of Manduca sexta; Dunn PE et al.; Both hemocytes and fat body from larvae of Manduca sexta, which have been injected with inducers of antibacterial protein synthesis, contain immunoreactive lysozyme . However, fat body is a richer source and has been demonstrated to synthesize and release lysozyme and cecropin-like peptides (bactericidins) in vitro . Fat body secretion of lysozyme and bactericidins is stimulated by addition of soluble peptidoglycan fragments to culture medium . The rate of lysozyme secretion by fat body varies as a function of peptidoglycan inducer concentration . These data are consistent with the hypothesis that, in vivo, bacteria must be phagocytized and partially degraded (processed) by hemocytes to generate a signal (peptidoglycan) that subsequently induces antibacterial protein synthesis by fat body.

Ciba Found Symp, 1985, 112, 242 - 70
Vaccine development for the control of cholera and related toxin-induced diarrhoeal diseases; Holmgren J et al.; The toxin-induced diarrhoeal diseases in greatest need of effective vaccines for use in control programmes are cholera and diarrhoea due to enterotoxigenic Escherichia coli . Such vaccines, whether consisting of inactivated immunogens or live attenuated organisms, should be administered by the oral route to stimulate the gut mucosal immune system to a maximal extent . For optimal efficacy they should probably contain or produce immunogens evoking both antibacterial and antitoxic immunity that can interfere in a synergistically cooperative manner with colonization as well as toxin action (binding) events in the pathogenesis . The actual or predicted advantages and limitations of oral vaccines based on protective antigen cocktails and different approaches to live, attenuated organisms are discussed . A conclusion is that effective vaccines could play an important role in the control of diarrhoeal disease by reducing mortality and morbidity, and ideally also the transmission of disease.

Tsitol Genet, 1985 Jan-Feb, 19(1), 24 - 6
{Modification of the cytogenetic effect of dioxidine in experimental alloxan diabetes in rats}; Zolotareva GN et al.; A dependence was established between the cytogenetic effect of dioxydinum antibacterial drug and the disturbance of carbohydrate metabolism in rats with alloxan diabetes.

Surg Annu, 1985, 17, 1 - 22
Wound healing in abdominal operations; Bucknall TE; For the practicing surgeon as yet there is no ideal suture and no perfect antibacterial substance . Therefore, the technique of wound and suture handling is extremely important . Gentleness is the key, and the surgeon should think in terms of what is happening to the cells in the area of repair . Gentleness will result in less dead tissue, fewer unwanted adhesions, less subsequent infection and, therefore, improved healing.

J Ocul Pharmacol, 1985 Winter, 1(4), 363 - 8
Trans-scleral iontophoresis of gentamicin; Burstein NL et al.; Bactericidal levels of gentamicin were obtained in vitreous humor by iontophoresis of antibiotic directly through the sclera . A silicone rubber tube of small diameter filled with gentamicin sulfate formed the electrode . A two milliampere current applied for three minutes to each of four perilimbal sites introduced gentamicin sufficient to maintain therapeutic levels for more than 24 hours . The proportion of drug reaching vitreous versus aqueous humor was dependent on electrode position relative to retina and pars plana . An endogenous antibacterial agent was apparently released during iontophoretic stimulation and interfered with the bacterial growth inhibition assay . Ketoconazole, a water-insoluble antifungal agent, has also been introduced successfully into vitreous humor by anodal iontophoresis after protonation in weak acid.

Arzneimittelforschung, 1985, 35(2), 543 - 6
{The effect of cefaclor, doxycycline and other oral antibiotics on phagocytosis of polymorphonuclear granulocytes and PHA-induced stimulation of blood lymphocytes in man}; Hahn H et al.; The influence of the orally applicable antibacterial agents, cefaclor (Panoral), doxycycline, erythromycin, and cotrimoxazole on phagocytosis by human neutrophil granulocytes was investigated . Further, the influence of cefaclor, erythromycin, and doxycycline on PHA stimulation of human blood lymphocytes was studied . Doxycycline (1 mg/ml) had strongly suppressive effects on phagocytosis, whereas cefaclor (1 mg/ml cotrimoxazole (0.1 mg/ml), and erythromycin (0.1 mg/ml) did not suppress phagocytosis . PHA-induced lymphocyte stimulation was strongly inhibited by doxycycline (10 micrograms/ml), whereas cefaclor (10 micrograms/ml) did not suppress at all . Erythromycin (10 micrograms/ml) exerted some inhibition (average 12.6%) . These results are discussed with respect to immunoneutrality of antibacterial agents.

Scand J Infect Dis Suppl, 1985, 46, 64 - 71
Antibacterial activity and pharmacokinetics of nitroimidazoles . A review; Bergan T; The antibacterial activity of metronidazole and tinidazole are comparable . The former is subject to biotransformation with the production of both hydroxy-metronidazole and acetylmetronidazole . The hydroxylated moiety has an antibacterial activity and may act either synergistically or additively in combination with metronidazole, thus enhancing the therapeutic activity of the latter . Metronidazole and tinidazole may be given both orally and parenterally . The bioavailability of oral doses of metronidazole is 88-95%, that of tinidazole 90% . Rectal suppositories have a bioavailability of 60-70% . The serum half-life of metronidazole is 6-10 hours, that of hydroxy-metronidazole 9.5-19 hours, and that of tinidazole 9-14 hours . The half-life may be longer in patients who have undergone colorectal surgery . Renal failure enhances the elimination of hydroxy-metronidazole and acetyl-metronidazole, whereas the consequences for unchanged metronidazole are negligible . The effect of reduced renal function on tinidazole is unclear . The extravascular penetration of metronidazole and tinidazole are similar . A single prophylactic intravenous dose of 1500 mg of either drug causes prolonged antibacterial effects which would last 36-48 hours for both drugs.

Eur J Respir Dis Suppl, 1985, 139, 113 - 6
Pharmacoprevention of tobacco smoke effects on macrophage cells; Green GM; Cigarette smoke components produce a variety of morphologic, physiologic, biochemical, and enzymatic changes in pulmonary alveolar macrophages, cells which are important in pulmonary antibacterial defenses, cellular regulatory activity, and tissue pathogenesis of inflammation, proteolysis and fibrogenesis . A common denominator of enzymes found to be inhibited by cigarette smoke components is a sulfhydryl moiety which is critical to the functioning of the enzyme and highly susceptible to oxidant activity of substances with the properties of agents in cigarette smoke . The inhibitory effect of cigarette smoke components on glyceraldehyde 3-phosphate dehydrogenase, calcium and magnesium ATPase, and endoperoxide E-isomerase is quantitatively prevented by the addition of sulfhydryl agents such as glutathione and cysteine . Furthermore, critical functions of whole cell activity such as phagocytosis, energy metabolism, and prostaglandin synthesis and release, functions which are dependent on sulfhydryl enzymes and are inhibited by cigarette smoke components, are protected when glutathione or cysteine are provided in advance of the exposure . These sulfhydryl agents also protect adhesion and cellular morphology from derangement by cigarette smoke components . These in vitro studies suggest a role for sulfhydryl-containing agents in the prevention of environmentally-induced injuries to alveolar macrophages.

Ann N Y Acad Sci, 1985, 446, 105 - 15
Synthetic polymers as drugs; Albertsson AC et al.; Biologically active compounds have been incorporated into synthetic polymers . Bithionol, a well-known and potent antibacterial agent, has been used as bisphenol monomers for polyesters, polyphosphates, and phosphonates; the bischloroformate of bithionol has been converted into copolycarbonates and polyurethanes . The copolycarbonates of bithionol, optimally designed polymer structures with poly(ethylene oxide) glycols as the other comonomer, have been hydrolyzed under physiological conditions at a degradation rate of about 1% per day . Primaquine, an antimalarial, and amantadine, an antiviral agent, when reacted with isocyanates gave polymeric biurets as do other primary aliphatic amines . Primaquine also underwent nucleophilic substitution reactions on polyepichlorohydrin . 3-Vinyl-, 4-vinyl-, and 5-vinylsalicylic acids have been synthesized, polymerized, and copolymerized to polymeric antibacterials . Copolymers of vinylsalicylic acid can be selective in their activity, depending on the comonomer . Selectivity can also be achieved by derivation of the poly(vinylsalicylic acid).

Jpn J Antibiot, 1985 Jan, 38(1), 31 - 40
{Studies on penetration of antibiotics to gallbladder tissue and bile, its surgical significance . Mainly with cefmenoxime}; Tsuburaya H et al.; Basic and clinical studies in 37 patients with biliary tract disease on comparison between cefmenoxime (CMX) and cefotiam (CTM) were studied and the following results were obtained . In vitro antibacterial activities of CMX and CTM against 25 strains (15 organisms) isolated from bile of patients with biliary tract disease were stronger than that of cefazolin (CEZ) . In cholecystectomized patients, CMX (2 g) or CTM (2 g) was injected intravenously, followed by determination of concentration in bile and gallbladder tissue about 2 hours after administration . In CMX administration, the mean concentration in gallbladder bile was 812.1 micrograms/ml, and the mean concentration in duct bile was 1,050.6 micrograms/ml, and the mean concentration in gallbladder tissue was 100.7 micrograms/g . In CTM administration, the mean values were, 1,092.5 micrograms/ml, 1,287.8 micrograms/ml, 28.5 micrograms/g, respectively . The concentration of CMX and CTM were almost similarly . The bile concentration of CMX (i.v.) was compared with CTM (i.v.) by cross-over method in cases of T-tube drainage . The peak bile concentrations of CMX and CTM were as high as 172.4 micrograms/ml and 182.2 micrograms/ml, respectively, 1 approximately 2 hours after 2 g intravenous administrations . Furthermore, the concentration of them were highly gained, 16.1 micrograms/ml of CMX and 33.8 micrograms/ml of CTM, even at 5 approximately 6 hours . In choledochostomized patients, CMX (4 g/day) was injected intravenously, followed by determination of concentration in intraperitoneal exudate . The mean concentration of CMX was 15.3 micrograms/ml on the first day after the operation, and 6.0 micrograms/ml even on the third day after the operation . Those results suggest that the high antibacterial activity of CMX against organism in bile and, the high penetration of CMX to bile, gallbladder tissue and intraperitoneal exudate will promise its important role in treatment of biliary tract infections.

J Dent Res, 1985 Jan, 64(1), 37 - 43
The effect of malnutrition on caries development and saliva composition in the rat; Johansson I et al.; The purpose of this study was to investigate the effect in rats of malnutrition on caries development and on some antibacterial substances in saliva . By gastric intubation, two groups of ten rats each were fed a liquid basic diet (100% diet), and two similar groups were fed the basic diet diluted with an equal volume of water to contain 50% of the nutrients of the basic diet (50% diet) . One group on undiluted and one group on the diluted basic diet were offered sucrose as a supplement by mouth 17 times daily, using a programmed feeding machine, and the other two groups were offered starch in a similar manner . The extent and depth of the caries lesions were five times greater in the low-nourished (50% diet) sucrose group in comparison with the group given the undiluted diet supplemented with sucrose . The 50% diet group ate more frequently from the offered supplement . The 50% diet induced lower salivary lactoperoxidase activities, and there was an additive effect of starch as supplement . Higher concentrations of sIgA were found in the saliva of animals fed the 50% diet supplemented with sucrose than in those fed sucrose and the 100% diet . Significantly greater levels of sIgA and IgG were found in the saliva from the 50% diet-sucrose group than in the 50% diet-starch group . Plaque scores differed slightly but not significantly between the groups . The starch group receiving 100% diet showed a slightly lower level of S . mutans infection as compared with the 50% diet-starch group; the caries scores in the starch groups did not differ.

Dev Comp Immunol, 1985 Summer, 9(3), 551 - 8
On the primary structures of lysozyme, cecropins and attacins from Hyalophora cecropia; Boman HG et al.; Diapausing pupae of Cecropia respond to a bacterial infection by the selective synthesis of RNA and 15-20 hemolymph proteins . Of these we have purified lysozyme and two classes of antibacterial proteins called cecropins and attacins . The primary structure has been determined for the lysozyme, one attacin and five cecropins . We have also prepared a cDNA bank, isolated and sequenced clones corresponding to the lysozyme, the two main attacins and one cecropin . The results of these structural studies are briefly summarized . Finally we review the solid phase synthesis of cecropin A and B and 9 analogs of cecropin A.

Polim Med, 1985, 15(3-4), 99 - 108
{Experimental studies of vascular prostheses made of plastics with antibacterial properties}; Sowinski A et al.; Bilaterally velour, polyester vascular prostheses were soaked with antibiotics: vibramicin, gentamicin and riphamicin . To obtain more stable binding of the prostheses with the antibiotics, physico-chemical modification of its surface was made . The prostheses retained their bacteriocidal properties even after 120 hours of being in the arterial system of a dog . Experiments of animals show the prostheses are effective in fighting back experimental infection.

Jpn J Antibiot, 1985 Jan, 38(1), 137 - 44
{Screening for the antagonizing agents against lethal toxicity of neocarzinostatin . I . Inhibitory effects of various drugs on the toxicity of neocarzinostatin in vitro and in vivo}; Ito A et al.; Neocarzinostatin (NCS) used for the chemotherapy of leukemia and cancers such as stomach, pancreas and bladder, has been pointed out to have the side effects mainly causing leukopenia . In order to prevent these side effects of NCS by systemic administration, we have attempted to inject NCS directly into the tumor tissues and to inactivate NCS leaked from the tissues by the treatment of antidotes for NCS . The present report deals with the influence of some antidotes on the toxicity of NCS in vitro and in vivo . The results demonstrated that; Four SH-compounds, such as thiopronin, glutathione (reduced form), sodium thioglycolate and L-cysteine monohydrochloride monohydrate were effective to inactivate antibacterial activity of NCS against M . luteus ATCC 9341 in vitro . It was recognized that acute toxicity of NCS was reduced by pretreatment of these SH-compounds and its action was dose related . The LD50 values of NCS intravenous administration in mice increased 5.8- to 24-fold when 150, 300, 500 and 1,000 mg/kg of thiopronin were administered intravenously 2 minutes prior to NCS . And 2.3- to 4.2-fold by 500 and 1,000 mg/kg of glutathione (reduced form), 1.6- to 4.2-fold by 50, 100 and 200 mg/kg of sodium thioglycolate, 1.9- to 4.2-fold by 100, 200 and 400 mg/kg of L-cysteine monohydrochloride monohydrate respectively . On the other hand, pretreatment of NCS didn't affect the acute toxicity of thiopronin.

Res Commun Chem Pathol Pharmacol, 1985 Jan, 47(1), 73 - 83
DNA binding, cardiac superoxide production and cytotoxicity of daunomycin analogs; Nachtman JP et al.; Pyridoanthraquinones are potent antibacterial agents especially against gram-positive organisms . We tested two major biologic actions of these compounds: DNA intercalation and superoxide (O2-) production in sarcosomes . Using the bathochromic and hypochromic shifts induced by intercalation, followed by Scatchard analysis, we calculated dissociation constants and the number of binding sites per base pair for several analogues . We compared O2- production using cytochrome c reduction . Unsubstituted compounds do not bind to DNA or change its melting temperature (Tm) . Placing a morpholino or piperidyl group at C-5 enhances the binding to DNA . The tetracyclic compounds were equipotent at producing O2- and were 20-fold more active than daunomycin . These compounds were unusual in their solid tumor cytotoxicity.

J Membr Biol, 1985, 84(2), 173 - 81
Channels formed by colicin E1 in planar lipid bilayers are large and exhibit pH-dependent ion selectivity; Raymond L et al.; The E1 subgroup (E1, A, Ib, etc.) of antibacterial toxins called colicins are known to form voltage-dependent channels in planar lipid bilayers . The genes for colicins E1, A and Ib have been cloned and sequenced, making these channels interesting models for the widespread phenomenon of voltage dependence in cellular channels . In this paper we investigate ion selectivity and channel size--properties relevant to model building . Our major finding is that the colicin E1 channel is large, having a diameter of at least 8 A at its narrowest point . We established this from measurements of reversal potentials for gradients formed by salts of large cations or large anions . In so doing, we exploited the fact that the colicin channel is permeable to both cations and anions, and its relative selectivity to them is a function of pH . The channel is anion selective (Cl- over K+) in neutral membranes, and the degree of selectivity is highly dependent on pH . In negatively charged membranes, it becomes cation selective at pH's higher than about 5 . Experiments with pH gradients cross the membrane suggest that titratable groups both within the channel lumen and near the channel ends affect the selectivity . Individual E1 channels have more than one open conductance state, all displaying comparable ion selectivity . Colicins A and Ib also exhibit pH-dependent ion selectivity, and appear to have even larger lumens than E1.

EMBO J, 1984 Dec 20, 3(13), 3347 - 51
The antibacterial effect of attacins from the silk moth Hyalophora cecropia is directed against the outer membrane of Escherichia coli; Engstrom P et al.; The attacins are antibacterial proteins which accumulate in the hemolymph of the giant silk moth, Hyalophora cecropia, in response to a bacterial infection . Here we show that the permeability barrier function of the outer membrane is affected shortly after addition of attacin to growing cultures of Escherichia coli . Specifically, the penetration through the outer membrane of beta-lactam antibiotics, chicken egg white lysozyme and the detergent Triton X-100 was found to be facilitated . The sensitivity of E . coli to cecropin B, another antibacterial protein present in the hemolymph of H . cecropia, was also found to be increased after treatment with attacin . The results suggest that the target of the attacins in E . coli is the outer membrane . Other effects of the attacins which have been observed are likely to be indirect consequences of the alteration in the properties of the outer membrane . These effects include changes in the cell shape, irregular patterns of cell division and lysis . The minimal concentration at which the attacins affected the growth of E . coli was 1 and 0.5 microM for the neutral (pI 7) and basic (pI 9) attacins, respectively, which corresponds to less than 2% of the concentration of the attacins in the hemolymph of infected pupae.

J Antibiot (Tokyo), 1984 Dec, 37(12), 1623 - 7
X-ray crystal structure of 4-deoxy-3'-bromopyrido{1',2'-1,2}imidazo{5,4-c}rifamycin S; Brufani M et al.; This paper reports the determination of the X-ray molecular structure of 4-deoxy-3'-bromopyrido{1',2'-1,2}imidazo{5,4-c}rifamycin S, carried out in order to unequivocally define the general structure of a new series of rifamycin SV derivatives, which are potent antibacterial agents, and are not absorbed at the gastroenteric level . They have been prepared by Alfa Farmaceutici, Bologna, by condensing 2-aminopyridine derivatives to 3-bromorifamycin S . The solid state X-ray study has confirmed the structure proposed on the basis of 1H NMR studies in solution . It has also shown that the newly formed pyridoimidazo system is in a mesomeric betaine form, the pyrido nitrogen being positively charged and the imidazo nitrogen being negatively charged . This feature is believed responsible for the pharmacokinetic behavior of these new drugs, one of which, denoted either as rifamycin L 105 or rifaximin, is actually under clinical trial as a topical intestinal disinfectant.

J Antibiot (Tokyo), 1984 Dec, 37(12), 1642 - 50
Correlations between CNDO/2 charge distribution and 13C NMR chemical shift in 7-acylamino side chains of cephalosporins; Graves BJ et al.; Molecular orbital calculations by the CNDO/2D method yield charge distributions which correlate well with the observed 13C NMR chemical shift for the amide carbon of acylamino side chains of cephalosporins . Acyl groups that withdraw electrons from the amide C-N bond and concomitantly make the amide nitrogen more negatively charged increase the chemical shift . The trends are related to the degree of amide resonance . No direct correlation was found between the chemical shift of the amide carbon and the antibacterial activity of the cephalosporins.

J Antibiot (Tokyo), 1984 Dec, 37(12), 1628 - 34
Syntheses of 23-deoxy-23-N-ethyl-23-(2-fluoro-, 2,2-difluoro-, and 2,2,2-trifluoroethyl)amino derivatives of mycaminosyl tylonolide and 4'-deoxymycaminosyl tylonolide; Sakamoto S et al.; Derivatives of mycaminosyl tylonolide (1) and 4'-deoxymycaminosyl tylonolide (2) containing N-ethyl-2-fluoro-, 2,2-difluoro- and 2,2,2-trifluoroethylamino groups at their C-23 have been prepared by treating 23-deoxy-23-ethylaminomycaminosyl tylonolide diethyl acetal (14) and its 4'-deoxy analog 15 with 2-fluoro-, 2,2-difluoro- and 2,2,2-trifluoroethyl trifluoromethanesulfonates . The relationship between the antibacterial activity and the numbers of the fluorine atoms introduced in the final products is discussed.

J Antibiot (Tokyo), 1984 Dec, 37(12), 1611 - 22
The synthesis of 4-deoxypyrido{1',2'-1,2}imidazo{5,4-c}rifamycin SV derivatives; Brufani M et al.; Two series of new semisynthetic rifamycin SV derivatives have been prepared . One of them bears a quaternary ammonium salt at C3 (1-5), and the other a pyridoimidazo system condensed at C3 and C4 (6-11) . While compounds 1-5 had poor antibacterial activity in vitro, compounds 6-11 were found to be highly active in vitro but poorly absorbed in vivo . They could thus have potential as agents in the therapy of intestinal infections . The synthesis and the 1H NMR structure determination of these new compounds are reported.

J Antibiot (Tokyo), 1984 Dec, 37(12), 1605 - 10
A sodium-containing polymyxin derived from polymyxin-complex during chromatography; Kitamura-Matsunaga H et al.; Commercial colistin (polymyxin E)-complex was separated into two major components (colistins A and B) on a preparative scale by HPLC (alkyl bonded silica and aqueous-organic mobile phase containing 0.2 M NaCl-HCl buffer (pH 2.0} . Desalting of the colistins A and B fractions was completed by reversed-phase adsorption and elution using methyl alcohol . In these experiments, it was inadvertently found that prolonged elution with water gave two hydrophilic peptides, which were tentatively named colistins AH and BH, respectively . Further elution with methyl alcohol produced two lipophilic peptides which were named colistins AL and BL . Colistin BH showed higher potency than colistin AH, AL or BL, and it was also effective in vivo . The fatty acid and amino acid composition of colistin BH was identical with that of colistin BL, but colistin BH contained a relatively large amount of nonionic sodium which scarcely responded to the sodium ion-selective electrode of an ion meter; colistin BH had a slightly lower molar extinction coefficient than the colistin BL which contained negligible amount of nonionic sodium . Colistin AH also contained nonionic sodium . Potassium containing colistins could also be derived from colistin-complex . These compounds could not be formed merely by adding sodium chloride or potassium chloride to colistin-complex solution . To obtain the sodium-containing compounds, contact with some hydrophobic stationary phase, such as alkyl-bonded silica or styrene-divinylbenzene copolymer, was necessary . It is postulated that one of the antibacterial mechanisms of polymyxin is associated with its complex-forming action on monovalent cations after contact with the lipid layer of the bacterial outer membrane.

J Med Chem, 1984 Dec, 27(12), 1740 - 3
Folate antagonists . 22 . Antimalarial and antibacterial effects of 2,4-diamino-6-quinazolinesulfonamides; Elslager EF et al.; The synthesis and antimalarial activity of a series of 2,4-diamino-6-quinazolinesulfonamides (III) is described . Chlorosulfonation of 2,4-quinazolinediamine affords the 6-sulfonyl chloride, which upon treatment with the appropriate amine produces the desired products . Alternatively the sulfonyl chloride could be introduced by diazotization of the corresponding amine followed by treatment with SO2 in the presence of CuCl2 . Although substantial antimalarial activity was demonstrated for several members of this class, studies were discontinued in light of the potency of related series.

J Ethnopharmacol, 1984 Dec, 12(3), 279 - 86
Antibacterial constituents in the essential oil of Cymbopogon citratus (DC.) Stapf; Onawunmi GO et al.; Cymbopogon citratus (DC.) Stapf., commonly known as lemon grass and used, over many years, for medicinal purposes in West Africa, produces a volatile oil on steam extraction of its leaves . The antibacterial properties of the essential oil have been studied . These activities are shown in two of the three main components of the oil identified through chromatographic and mass spectrometric methods . While the alpha-citral (geranial) and beta-citral (neral) components individually elicit antibacterial action on gram-negative and gram-positive organisms, the third component, myrcene, did not show observable antibacterial activity on its own . However, myrcene provided enhanced activities when mixed with either of the other two main components identified.

J Med Chem, 1984 Dec, 27(12), 1737 - 9
Synthesis and biological evaluation of 6-amino-1H-pyrrolo{3,2-c}pyridin-4(5H)-one (3,7-dideazaguanine); Schneller SW et al.; The synthesis of 6-amino-1H-pyrrolo{3,2-c}pyridin-4(5H)-one (3,7-dideazaguanine, 2) has been accomplished from 3-(ethoxycarbonyl)pyrrole-2-acetonitrile . In contrast to 3-deazaguanine, compound 2 did not show any antitumor, antiviral, or antibacterial properties . Furthermore, it was not a substrate for hypoxanthine-guanine phosphoribosyltransferase or purine nucleoside phosphorylase.

J Med Chem, 1984 Dec, 27(12), 1543 - 8
Pyridonecarboxylic acids as antibacterial agents . 4 . Synthesis and antibacterial activity of 7-(3-amino-1-pyrrolidinyl)-1-ethyl-6-fluoro-1,4 -dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid and its analogues; Egawa H et al.; The title compounds (28-56) with an amino- and/or hydroxy-substituted cyclic amino group at C-7 were prepared with 1-substituted 7-chloro-, 7-(ethylsulfonyl)-, and 7-(tosyloxy)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3- carboxylic acids and their ethyl esters (3-7) with cyclic amines such as 3-aminopyrrolidine . The N-1 substituent includes ethyl, vinyl, and 2-fluoroethyl groups . As a result of in vitro and in vivo antibacterial screenings, three compounds, 1-ethyl- and 1-vinyl-7-(3-amino-1-pyrrolidinyl)-6-fluoro- 1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids (33a and 33b) and 1-vinyl-7-{3-(methylamino)-1-pyrrolidinyl} analogue 34b, were found to be more active than enoxacin (2) and to be worthy of further biological study . Structure-activity relationships are discussed.

J Dairy Sci, 1984 Dec, 67(12), 2863 - 72
Biochemical and antibacterial properties of bovine mammary secretion during mammary involution and at parturition; Nonnecke BJ et al.; Mammary secretions from four Holstein Friesian cows were collected during late lactation, early involution, and early in subsequent lactation . Changes of pH, concentration of serum albumin, immunoglobulin G, citrate, lactoferrin, and number of leukocytes in secretions were typical of milk from glands undergoing these physiological transitions . Whey prepared from a cow's secretions was evaluated for its capacity to inhibit growth of Escherichia coli, 60-Lilly, and a coliform strain isolated from mammary secretions of that cow . Wheys from different glands of the same cow differed markedly in their capacity to inhibit growth of coliforms . Inhibition of both strains by the wheys increased significantly during the dry period and was maximal in wheys collected day 15 of the dry period and at parturition in the subsequent lactation . The coliform strain isolated from a specific cow was inhibited more than Escherichia coli, 60-Lilly, by whey from the specific cow . Inhibition of the cow-specific coliform strain by the day 15 whey was reduced significantly after addition of ferric iron or sodium citrate . Addition of excess ferric iron or citrate to wheys collected at parturition did not alter significantly their inhibitory capacity within cow . However, reduction of growth inhibition was significant when data from the four cows were pooled.

Clin Otolaryngol, 1984 Dec, 9(6), 315 - 21
Intracranial suppuration 1968-1982--a 15 year review; Small M et al.; The CT scanner and the recognition of anaerobic organisms has altered the investigation and management of intracranial suppuration . Improved treatment of acute and chronic middle ear infection has also occurred . A 15 year retrospective review was undertaken to assess the effects of these changes . The ears and sinuses were confirmed as the major source of intracranial suppuration (69%) although initial presentation to ENT surgeons was less common (14%) . Ear complications occur in childhood and in the fifth and sixth decades; sinus complications predominantly in the second and third decades . The incidence of sinus infection appears to be rising . With the introduction on the CT scanner cerebral abscess mortality declined from 27.5% to 6.5% and subdural abscess mortality halved . The introduction of metronidazole contributed to a drop in mortality . The use of the CT scanner and more accurate antibacterial treatment, including metronidazole, gives hope for a more successful outcome than was previously possible.

Zentralbl Bakteriol Mikrobiol Hyg {A}, 1984 Dec, 258(2-3), 275 - 82
Analysis of cephalosporin-induced changes in the volume distribution of Escherichia coli cultures by an electronic counter-channelanalyser; Schulz E et al.; The demonstration of morphological alterations of the bacterial cell together with bactericidal kinetics are of value for the description of the antibacterial activity of beta-lactam antibiotics . One of the indicators of antibiotic effect on bacterial morphology is the change in bacterial cell volume . This can be demonstrated graphically and numerically by means of electronic cell counting and volume distribution analysis using the Coulter Counter-Channelanalyser system connected to a computer . After registration of the distribution of the relative volume of the Escherichia coli population, the mean cell volume was calculated . The latter parameter increased more than 6 fold with increasing cefotaxim-exposure times . The onset of the delayed (2 h after cefotaxim administration) bacteriolytic effect was reorganized by the appearance of small cell breakdown particles and quantified by counting . In order to demonstrate the therapeutic process graphically the distribution curves were transformed to a common scale . Since a complete storage of the data per sample is performed normally within one minute, the Coulter Counter-Channelanalyser technique can be carried out simultaneously with the bactericidal kinetic experiment . The data demonstrate the speed and intensity of the morphological cell alterations induced by the beta-lactam antibiotic.

Jpn J Antibiot, 1984 Dec, 37(12), 2457 - 77
{Basic and clinical evaluation of sulbactam/cefoperazone in the field of pediatrics}; Toyonaga Y et al.; Sulbactam (SBT) in a novel beta-lactamase inhibitor from Pfizer and combined with cefoperazone (CPZ) ina 1:1 ratio (SBT/CPZ) . Fundamental and clinical studies on SBT/CPZ were executed . The antibacterial activity of SBT/CPZ was compared with those of SBT, CPZ and CEZ against clinical isolates of S . aureus and E . coli which were not susceptible to CEZ . SBT alone did not show any activity against S . aureus, MICs against all strains were over than 100 micrograms/ml on the inoculations of undiluted and 100-fold diluted specimen . CPZ showed MICs over than 100 micrograms/ml against approximately 70% of the isolates on the undiluted inoculation, and on the 100-fold diluted inoculation, the MIC50 and MIC70 were 12.5 micrograms/ml and 100 micrograms/ml, respectively . SBT/CPZ showed better activity than CPZ by 2-8 folds against the strains highly resistant to CPZ; the MIC50 on the undiluted inoculation was 50 micrograms/ml . Against E . coli, the characteristic of SBT/CPZ was shown more clearly . The MICs of CPZ were over than 100 micrograms/ml against approximately 70% of the isolates on the undiluted inoculation, but SBT/CPZ showed MIC50 at 25 micrograms/ml . On the 100-fold diluted inoculation, SBT/CPZ was 4 approximately 8-fold superior than CPZ against strains on which MICs of CPZ were over than 12.5 micrograms/ml . Serum levels were determined by a bolus intravenous injection and by intravenous drip infusion of 10, 20, 40 mg/kg of SBT/CPZ . When administered by a bolus injection, the peak level was seen at 30 minutes in most patients: 8.7, 14.7 or 27.0 micrograms/ml of SBT and 30.1, 42.5 or 76.4 micrograms/ml of CPZ were detected with the 3 different doses . These levels were dose-dependent, and decreased slowly to 0.3, 0.3 or 0.3 micrograms/ml of SBT and 2.9, 2.8 or 3.3 micrograms/ml of CPZ at 6 hours after administration . Half-lives were 1.39, 1.20 or 0.98 hour for SBT and 1.77, 1.59 or 1.42 hours for CPZ . The same 3 doses were given by intravenous drip infusion . The peak levels obtained at the end of infusion (1 hour after initiation of infusion) were 15.3, 14.4 or 43.2 micrograms/ml for SBT and 33.4, 38.2 or 104.2 micrograms/ml for CPZ, respectively . The levels were somewhat low in 20 mg/kg group . After the end of infusion, these levels decreased fairly rapidly, and after 6 hours almost the same levels of 0.4, 0.5 or 0.3 micrograms/ml for SBT and 1.4, 3.9 or 3.3 micrograms/ml for CPZ were detected.(ABSTRACT TRUNCATED AT 400 WORDS)

Jpn J Antibiot, 1984 Dec, 37(12), 2420 - 6
{Pharmacokinetics of ceftriaxone in the peripheral venous serum, uterine arterial serum and intrapelvic genital organs}; Miyakawa I et al.; The concentrations of ceftriaxone (Ro 13-9904, CTRX) in peripheral venous serum, uterine arterial serum and intrapelvic genital organs were determined by bioassay, using the cylinder-plate diffusion method, in 26 women with simple total hysterectomy . With an intravenous injection of CTRX 1 g, the maximum levels of peripheral venous serum and uterine arterial serum were 116.23 micrograms/ml and 112.76 micrograms/ml, respectively . Also, the biological half-life (T 1/2) was 6.85 hours in peripheral venous serum and 7.31 hours in uterine arterial serum . The concentrations of CTRX in peripheral venous and uterine arterial serum were more than 7.8 micrograms/ml at 24 hours after injection and maintained at a higher level than the minimal inhibitory concentration necessary for most E . coli strains for at least 24 hours . The concentrations of CTRX in intrapelvic genital organs were kept higher than the minimal inhibitory concentration against E . coli at 24 hours after injection, and the ratios of the concentrations in uterine tube and endometrium to that of in peripheral venous serum were 0.474 +/- 0.080 and 0.272 +/- 0.087, respectively . Since CTRX is characterized by more potent antibacterial activity than some other antibiotics and the long-acting efficacy, intravenous administration of CTRX at 1 g or 2 g per day may be an adequate dose for infections of the female urogenital tract.

Eur J Clin Microbiol, 1984 Dec, 3(6), 566 - 7
Influence of culture medium and inoculum size on susceptibility of Bordetella pertussis to antibacterial agents in vitro; Zackrisson G et al.; Experimental examples of different beta-lactam--organism combinations in vitro and in vivo are presented to demonstrate that a rationale for dosage regimens of antibiotics should not be based solely on pharmacokinetic parameters . The time course of the pharmacological response (onset and speed of bacterial killing) and the presence or absence of a postantibiotic effect must also be considered . such pertinent information can be derived from in vitro studies such as time-kill curves and regrowth curves of bacteria obtained at and after short exposure of the target organisms to various concentrations of the drug.

Infect Immun, 1984 Dec, 46(3), 625 - 30
Comparative superoxide-generating system of granulocytes from blood and peritoneal exudates; Zimmerli W et al.; Blood polymorphonuclear leukocytes (PMN), upon interaction with specific chemotactic stimuli, leave the blood stream and migrate to tissues . At such a location, and upon contact with invading microorganisms, they generate superoxide (O2-) as a part of the respiratory burst of phagocytosis . We have compared the O2(-)-generating system of guinea pig peritoneal exudate PMN with that of peripheral blood PMN from the same species or of human origin . The rate of O2- production by casein-induced guinea pig exudate cells in response to a particulate stimulus (opsonized zymosan) was significantly decreased when compared with peripheral blood PMN . Furthermore, the activation time of the O2(-)-generating system was shorter in exudate than in peripheral blood PMN . Important differences in sensitivity to a metabolic inhibitor were found: (i) N-ethylmaleimide increased the activation time of the O2(-)-generating system only in guinea pig exudate cells and not in blood cells; (ii) when N-ethylmaleimide was added after complete activation of the PMN, the O2- production rate was inhibited in guinea pig as well as human blood PMN, but not in guinea pig exudate PMN . We conclude that exudation markedly alters one of the most important antibacterial mechanisms of PMN, the superoxide-generating system.

Experientia, 1984 Nov 15, 40(11), 1273 - 5
Tetracyclines inhibit parathyroid hormone-induced bone resorption in organ culture; Gomes BC et al.; Several tetracyclines (minocycline, doxycycline, tetracycline), in levels approximating physiologic concentrations, were found to inhibit parathyroid hormone-induced bone resorption in organ culture; the specificity of this effect was demonstrated by comparison with other (non-tetracycline) types of antibiotics . The ability of tetracyclines to inhibit bone resorption is consistent with the recent proposal by Golub et al . that these antibiotics can inhibit mammalian collagenolytic enzymes by a mechanism unrelated to the drug's antibacterial efficacy, a property which could be therapeutically useful in diseases characterized by excessive collagen breakdown.

Srp Arh Celok Lek, 1984 Nov-Dec, 112(11-12), 1197 - 204
{Contraceptive agents for men}; Primorac M et al.; PIP: Contraceptive drugs for men can control fertility by interrupting the process of spermatogenesis, preventing the maturation of spermatozoids, acting on the transportation of sperm, and by producing specific antispermal antibodies (immunologic fertility control) . The effect of various steroid and nonsteroid substances on the process of spermatogenesis has been studied . A combination of gestagens and androgens has been studied as a basis for male contraception . The latest publication by M . Kuhl and his collaborators describes very good results achieved by the use of dimeric ethynoidol testosterone ester in rats . D.J . Patanelli and M . Jackson have carefully examined the antitumor, antibacterial, and antiprotozoal agents . Further substances that have been studied are modified sugars and gossypol . A lot of attention has been paid lately to the effect of some alkalizing agents on the maturation of spermatozoids . K.R . Kedia and C . Markland have emphasized the importance of adrenergic system in the process of ejaculation . The effect of the antihypertension agent guanethidine, bretilium, and betanedin, as well as of some psychoactive durgs on the same process has also been studied . Active immunization of monkeys with follicle-stimulating hormone for two years has shown significant suppression of spermatogenesis . A.C . Menge and B . Fuller have explained specific immunologic traits of testis antigens in man, chimpanzee, rhesus monkey, and baboon . Studies in the area of male contraception published so far show that the stage leading to the formulation of drugs for wide-scale distribution has not yet been reached .

Pharmazie, 1984 Nov, 39(11), 745 - 7
Synthesis of some bergapten and ammajin derivatives with potential antibacterial activity; El-Sharief AM et al.; The reaction of bergapten and ammajin with chlorosulfonic acid i shown to give the sulfonyl chlorides 1 and 11 which react with aliphatic, aromatic, and heterocyclic amines to give the corresponding sulfonamides . Phenols also react with 1 and 11 to give the sulfonate esters 5 and 15 . Interaction of bergapten with phosphorous(V)sulfide gave the thione 7 which on reaction with amines gave 9 . The antibacterial activity of the products is reported.

J Cardiovasc Surg (Torino), 1984 Nov-Dec, 25(6), 489 - 97
Light and electron microscopic studies of an antibiotic bonded vascular graft; Greco RS et al.; Polytetrafluoroethylene grafts were bonded to oxacillin with the cationic surfactant, benzalkonium chloride . Grafts were placed in the canine aorta and harvested six and twelve weeks after implantation . Light and scanning and transmission electron microscopy were performed in all specimens . No histological differences could be demonstrated between control and antibiotic bonded grafts . Significant antibacterial activity was demonstrated at the time of graft implantation . However, none remained six and twelve weeks later.

Clin Orthop, 1984 Nov, (190), 75 - 82
The principles of the use of preventive antibiotics; Mader JT et al.; Antibiotic prophylaxis is indicated only under specific surgical settings . Appropriate antibiotic prophylaxis must take into account the type of surgery, the competence of the host, and the pharmacologic properties of the antibiotic(s) . The antibiotic should be given before the surgical procedure and have an antibacterial spectrum that covers the majority of the bacterial organisms anticipated at surgery . If there is doubt about the efficacy, antibiotic prophylaxis should not be initiated.

J Antibiot (Tokyo), 1984 Nov, 37(11), 1403 - 13
Structure-activity relationships on the terminal D-amino acid moiety of a novel cephamycin MT-141; Inouye S et al.; The effect of chemical modification of the D-amino acid function, which represents the C-7 beta substituent of cephamycin MT-141 on in vitro antibacterial activity was examined . MT-141 was more active on Gram-negative organisms than Gram-positive ones . It showed strong bacteriolytic activity on Gram-negative organisms . Lysis of Escherichia coli K-12 strain JE1011 treated with a low concentration of this antibiotic was preceded by frequent formation of multiple bulges from the cells . Amidation or decarboxylation, removing the acidic function from the D-amino acid of MT-141, resulted in an increase in activity against Gram-positive bacteria, and a decrease against Gram-negative ones . Cells treated with the amide or the decarboxylate did not form multiple bulges but formed single bulges . N-Acetylation of the D-amino acid moiety removing the basic function, caused a marked drop in activity against both Gram-positive and Gram-negative bacteria . The bacteriolytic activity on E . coli was reduced, and cells treated with the N-acetate became filamentous . Conversion of the D-amino acid function of MT-141 to the L configuration caused a moderate drop in activity against both Gram-positive and Gram-negative organisms . Both bacteriolytic and bactericidal activities against E . coli were reduced in the L-congener . Cefoxitin, cefmetazole and latamoxef used as reference antibiotics were less active than MT-141 in the bactericidal activity against E . coli, and induced single bulge formation or filamentation of the cells around MIC levels . Cell-surface permeability, stability to beta-lactamases, and binding affinity to PBPs of E . coli did not differ between MT-141 and its derivatives.

Ann Thorac Surg, 1984 Nov, 38(5), 494 - 9
Comparison of biopsy-proven Pneumocystis carinii pneumonia in acquired immune deficiency syndrome patients and renal allograft recipients; Sterling RP et al.; Pneumonia unresponsive to antibacterial agents in patients with acquired immune deficiency syndrome (AIDS) has become a new indication for lung biopsy . In 14 patients, transbronchial or open-lung biopsy demonstrated Pneumocystis carinii . An additional 12 patients, who were immunosuppressed after renal transplantation, were seen with P . carinii pneumonia . The diagnosis was established by transbronchial biopsy in the majority of patients . All patients were treated initially with trimethoprim plus sulfamethoxazole . Pentamidine was added after diagnosis if improvement did not occur . Both groups demonstrated reversal in the T cell helper: suppressor ratio . We compared these two groups of immunocompromised patients with respect to clinical presentation, lung pathology, response to therapy, and survival . Patients with AIDS were seen with a two- to three-week prodrome of fever, lymphadenopathy, weight loss, and malaise followed by hypoxia and leukopenia within 12 hours . Transplant patients became acutely ill with fever and hypoxia within 24 to 36 hours . In both groups, chest roentgenogram showed bilateral diffuse infiltrates; sputum cultures were generally negative; and lung biopsy demonstrated Gomori-Jones periodic acid-methenamine-silver-positive P . carinii . Mortality was substantially higher in patients with AIDS (50% versus 8%) . This difference may be explained by the fact that the T cell defect in AIDS has an infectious cause, while the defect in the renal allograft recipient is pharmacologically mediated.

Jpn J Antibiot, 1984 Nov, 37(11), 2060 - 82
{Fundamental and clinical evaluation on ceftriaxone in the pediatric field}; Toyonaga Y et al.; Fundamental and clinical evaluation on ceftriaxone (Ro 13-9904, CTRX) was performed . CTRX was compared with CEZ, CMZ, CTX and LMOX in the antibacterial activity against the clinical isolates such as S . aureus, E . coli, P . mirabilis, K . pneumoniae and S . marcescens . Against S . aureus, the MIC of CTRX ranged from 0.2 to greater than 100 micrograms/ml with a peak of 3.13 micrograms/ml, showing that CTRX was almost equal to CTX in activity, slightly superior to LMOX and much inferior to CMZ and CEZ, although some strains were not susceptible to CEZ . Against the intestinal strains of E . coli, K . pneumoniae and P . mirabilis, the MIC distribution of CTRX was similar to that of CTX and LMOX while CTRX showed the MIC as high as 3.13 micrograms/ml or above against 44% of all strains including the beta-lactamase producing strains of E . coli and K . pneumoniae, indicating a slight tendency of their becoming resistant . The MIC peaks against E . coli, K . pneumoniae and P . mirabilis were less than or equal to 0.1, 0.39 and less than or equal to 0.1 microgram/ml, respectively . As to S . marcescens which is drawing attention as a causative agent for infections inside of hospitals or those among young infants, CTRX inhibited 84% of the strains at 3.13 micrograms/ml, showing a definite superiority to CEZ and CMZ and a slight superiority to CTX and LMOX . The serum concentration after a single intravenous injection with 40 mg/kg reached a mean peak of 168.8 micrograms/ml at the first blood sampling (at 30 minutes) and gradually decreased to 137.5 micrograms/ml at 1 hour, 30.9 micrograms/ml at 6 hours, 12.6 micrograms/ml at 12 hours and 3.8 micrograms/ml at 24 hours, while the half-life time was 6.0 hours . The comparison of the serum level by 1 hour intravenous drip infusion between the dosage groups of 20 mg/kg and 40 mg/kg revealed that the former group reached a peak of 85.4 micrograms/ml at the termination of drip while the latter's peak was 176.6 micrograms/ml observed during the drip (30 minutes after the initiation of drip) . The respective levels of the 2 groups were 15.4 and 32.1 micrograms/ml at 6 hours, 5.1 and 15.0 micrograms/ml at 12 hours, and 1.6 and 4.1 micrograms/ml at 24 hours, indicating a distinct dose-response 2 hours after the initiation of drip administration . The half-life times were 4.9 and 6.2 hours, respectively, which are the longest among the cephalosporins presently being developed.(ABSTRACT TRUNCATED AT 400 WORDS)

Jpn J Antibiot, 1984 Nov, 37(11), 2027 - 33
{Clinical evaluation of ceftriaxone in the pediatric field}; Hoshina H et al.; Ceftriaxone CTRX was evaluated about its antibacterial activity against clinical isolates at our department and tried clinically in 10 children of 6 months to 10 years and 6 months of age . The antibacterial activity was equal to cefotaxime or higher while the clinical results were almost satisfactory . Three out of 4 strains were eradicated (75%) . As to the adverse reaction, eosinophilia was observed only in 1 case.

Am J Med, 1984 Oct 30, 77(4D), 44 - 8
Treatment and prevention of oropharyngeal candidiasis; Quintiliani R et al.; As more potent antibacterial drugs are used to combat infections and as more patients with impaired defenses against infection are treated, other organisms, like fungi, have become important pathogens . Fungi of all types may appear in this setting, but Candida species are the most common, usually beginning as an infection in the oropharynx . Although oropharyngeal candidiasis usually remains localized, it may spread elsewhere, leading to a fatal outcome . Controversy still exists regarding the best drug to prevent or treat oropharyngeal candidiasis, but clotrimazole given as a troche may be the best choice at the moment owing to its high clinical success rate, safety, cost effectiveness, and high patient acceptability . There remains a need for more randomized and controlled studies comparing the efficacy of nystatin, ketoconazole, and clotrimazole in high-risk patients in whom invasive candidiasis remains a frequent problem.

Biochemistry, 1984 Oct 23, 23(22), 5118 - 22
Substrate specificities and structure-activity relationships for acylation of antibiotics catalyzed by kanamycin acetyltransferase; Radika K et al.; Antibiotic resistance caused by the presence of the plasmid pMH67 is mediated by the aminoglycoside acetyltransferase AAC(6')-4, also known as kanamycin acetyltransferase . Bacteria harboring the plasmid are resistant to the kanomycins plus a broad range of other deoxystreptamine-containing aminoglycosides but not to the gentamicins XK62-2 and C1 which are substituted at the 6'-position . Substrate specificity studies on the purified enzyme, however, now show that the enzyme acetylates an even broader range of aminoglycosides, including the gentamicins XK62-2 and C1 . The enzyme also accepts several acyl-CoA esters, which differ in nucleotide as well as in acyl chain length . Application of the method of analysis of structure-activity data developed earlier for gentamicin acetyltransferase {Williams, J . W., & Northrop, D . B . (1978) J . Biol . Chem . 253, 5908-5914} to the kinetic data obtained for AAC(6')-4 shows that the turnover of the acylation reaction is limited by catalysis and not by the rate of release of either the acetylated antibiotic or CoA . Most structural changes in aminoglycosides cause changes in rates of release, and only drastic changes, near the 6'-amino group, affect catalysis . The structural requirements on aminoglycosides for enzymatic activity run parallel to the structural requirements for antibacterial activity.

Schweiz Med Wochenschr, 1984 Oct 6, 114(40), 1382 - 6
{Septic granulomatosis in adults}; Hoger P et al.; Chronic granulomatous disease is a usually X-linked disorder of granulocyte bacterial killing . At least 8 variants can be distinguished biochemically . Two male patients aged 20 and 24 years with a relatively benign clinical course are presented . A partial defect of the membrane-bound cytochrome b-245 with a residual bactericidal capacity was detected in both . Due to continuous antibacterial prophylaxis (trimethoprim/sulfamethoxazol) and treatment of infections with intracellularly accumulating agents (e.g . rifampicin, fosfomycin, clindamycin), even patients with complete defects of bacterial killing can reach adulthood today . Physicians and surgeons should be aware of this disorder, which is no longer a "fatal granulomatous disease of childhood".

J Antibiot (Tokyo), 1984 Oct, 37(10), 1144 - 8
A new indole N-glycoside antibiotic SF-2140 from an Actinomadura . I . Taxonomy and fermentation of producing microorganism; Tohyama H et al.; A new indole N-glycoside antibiotic SF-2140 which shows antiviral and weak antibacterial activity has been obtained from the cultured broth of an actinomycete strain . Strain SF-2140, designated Actinomadura albolutea sp . nov., was isolated from a soil sample collected in Hyogo Prefecture, Japan.

J Clin Invest, 1984 Oct, 74(4), 1269 - 79
Characterization of the extracellular bactericidal factors of rat alveolar lining material; Coonrod JD et al.; The surfactant fraction (55,000-g pellet) of leukocyte-free rat bronchoalveolar lavage fluid contains factors that rapidly kill and lyse pneumococci . These factors were purified and identified biochemically by using a quantitative bactericidal test to monitor fractionation procedures . 91% of the antipneumococcal activity of rat surfactant was recovered in chloroform after extraction of rat surfactant with chloroform-methanol (Bligh-Dyer procedure) . After chromatography on silicic acid with chloroform, acetone, and methanol, all detectable antibacterial activity (approximately 80% of the initial activity) eluted with the neutral lipids in chloroform . When rechromatographed on silicic acid with hexane, hexane-chloroform, and chloroform, the antibacterial activity eluted with FFA . Thin-layer chromatography (TLC) established that the antibacterial activity was confined to the FFA fraction . Gas-liquid chromatography showed that the fatty acid fraction contained a mixture of long-chain FFA (C12 to C22) of which 66.7% were saturated and 32.4% were unsaturated . The quantity of TLC-purified FFA needed to kill 50% of 10(8) pneumococci under standardized conditions (one bactericidal unit) was 10.6 +/- 0.5 micrograms . Purified FFA acted as detergents, causing release of {3H}choline from pneumococcal cell walls and increased bacterial cell membrane permeability, evidenced by rapid unloading of 3-O-{3H}methyl-D-glucose . FFA acting as detergents appear to account for the bactericidal and bacteriolytic activity of rat pulmonary surfactant for pneumococci.

Farmaco {Sci}, 1984 Oct, 39(10), 888 - 900
Pyrrolnitrin analogues . IX . Synthesis and biological activity of 1-tolyl-3-nitrophenyl-5-methylpyrazole-4-carboxylic acids and 1-tolyl-3-methyl-5-nitrophenylpyrazole-4-carboxylic acids; Cecchi L et al.; The syntheses of all the possible 1-tolyl-3-nitrophenyl-5-methylpyrazole-4-carboxylic acids, 1-tolyl-3-methyl-5-nitrophenylprazole-4-carboxylic acids and of the corresponding carboxylates are reported . Several 1,3- and 1,5-diarylpyrazole derivatives were subjected to in vitro antibacterial screenings . Some acids showed activity against some strains of gram-positive bacteria . The results are discussed on the basis of structure-activity relationships.

Invest Ophthalmol Vis Sci, 1984 Oct, 25(10), 1156 - 60
Nonlysozyme antibacterial factor in human tears . Fact or fiction?
Janssen PT, Muytjens HL, van Bijsterveld OP.
The existence of nonlysozyme antibacterial activity in tear fluid was reinvestigated . Tear fluid was fractionated by ultrafiltration and affinity chromatography . The antibacterial activity, detected in native tear fluid, coincided with the presence of lysozyme in the fractions . No antibacterial activity could be detected by agar diffusion in the fractions that should contain the low molecular mass antibacterial factors of tear fluid, reported in the literature.

J Antimicrob Chemother, 1984 Oct, 14(4), 313 - 27
Structure activity relationships among the monobactams; Bonner DP et al.; The monobactam nucleus (3-AMA) exhibits weak antibacterial activity and thus, as with the penicillins and cephalosporins, molecular substitution around the central nucleus is essential to realize the antibacterial potential of these molecules . Side chain structure/activity relationships in monobactams parallel those of the penicillins and cephalosporins . Such a relationship is not unexpected in view of the common enzymatic targets shared by these structurally divergent types . Side chain substitution of the monobactam nucleus leads to compounds exhibiting primarily Gram-positive, primarily Gram-negative or broad-spectrum activity . However, incorporation of small polar groups (amino, hydroxyl, carboxylic or sulphonic) at the alpha position of these side chains leads to poorly active compounds . This observation is the most striking divergence between monobactam and penicillin/cephalosporin structure-activity relationships . The most striking gain in anti-bacterial activity is observed with the introduction of an aminothiazoleoxime side chain as the 3-acyl substituent . In the case of carbonyl-activated and phosphate activated compounds, there is total reliance on this side chain grouping for achieving activity . Activity against Gram-positive bacteria, if present, is closely related to the nature of the acyl side chain . The aminothiazoleoxime side chains characteristically reduce activity against this organism class . Substitution at the 4-position of the monocyclic ring although capable of producing dramatic changes in biological activity, is highly unpredictable . In the SO3-activated molecules 4-substitution is essential for beta-lactamase stability and in many instances results in increased intrinsic activity of the molecule . Incorporation of 4-substituents on the beta-lactamase susceptible O-activated molecules has little or no effect on beta-lactamase stability or antibacterial activity . In the case of carbonyl- and phosphate-activated species, while offering no advantages, 4-substitution in many instances is highly deleterious to the activity of the molecule . The 'activating' group on the beta-lactam nitrogen, responsible for the activation of the beta-lactam ring can be varied quite widely while retaining high intrinsic activity . The O-activated compounds although showing the potential for broad-spectrum activity are beta-lactamase unstable, while the beta-lactamase stable compounds tend to show preferential activity against Gram-negative rods . There can be little doubt that additional activating groups will be incorporated on the monocyclic beta-lactam ring and it will be interesting to see what additional properties can be achieved by this approach.

Clin Haematol, 1984 Oct, 13(3), 587 - 98
New antibacterial agents: the role of new penicillins and cephalosporins in the management of infection in granulocytopenic patients; Klastersky J; The result of the introduction of the new acyl-penicillins and the new cephalosporins has not, so far, been a major breakthrough in the empirical therapy of febrile episodes and infections in granulocytopenic patients . It remains to be seen whether other cephalosporins such as cefoperazone and ceftazidime will perform better in the future . Ceftazidime alone or in combination with aminoglycosides shows very promising early results . My present recommendation for empirical therapy in febrile neutropenic patients is to use a combination of a penicillin or a cephalosporin active against P . aeruginosa with an aminoglycoside . Special attention should be paid to the emergence of penicillin- and/or cephalosporin-resistant strains . Empirical therapy should be with antibiotics to which resistance is as rare as possible . In this respect, the newer compounds may play a role in the future . It should also be emphasized that clinical information about new drugs is at present based on the study of relatively small groups of patients . Larger studies performed in more homogeneous groups are needed better to define the role of new agents.

Jpn J Antibiot, 1984 Oct, 37(10), 1973 - 6
{Clinical evaluation of sulbactam/cefoperazone in the field of obstetrics and gynecology}; Yabuki Y et al.; One or 2 grams of sulbactam/cefoperazone (SBT/CPZ) in 250 ml of 5% glucose solution was administered twice daily by drip infusion to 10 patients with female genital organ infections . The clinical effectiveness was seen in 8 patients but not in 2 patients associated with emergence of replaced organism or non-eradicated causative organism . Antibacterial activity of SBT/CPZ vs . CPZ in the 20 clinical isolates revealed that SBT/CPZ was 1 or 3 tubes superior to CPZ alone in the beta-lactamase producing organisms, but, 1 or 2 tubes inferior to CPZ in the beta-lactamase non-producing organisms . In 1 case increases in GOT and GPT, and in another increases in GOT and GPT, and a decrease in platelets were observed even though their degrees were mild.

Jpn J Antibiot, 1984 Oct, 37(10), 1880 - 92
{Laboratory and clinical studies of sulbactam/cefoperazone in the pediatric field}; Nishimura T et al.; The authors have carried out the laboratory and clinical studies of sulbactam/cefoperazone (SBT/CPZ) and obtained the following results . The antibacterial activities of SBT/CPZ against the clinical isolates of S . aureus, E . coli, K . pneumoniae, E . cloacae, E . aerogenes, S . marcescens, P . aeruginosa were measured by the plate dilution method with inoculum size of 10(6) cells/ml . The susceptibility distribution of S . aureus to SBT/CPZ ranged from 0.39 to 6.25 micrograms/ml, and the peak of distribution was 1.56 micrograms/ml . The peak of susceptibility distribution of K . pneumoniae was 0.20 microgram/ml, and the distribution of E . coli and E . aerogenes ranged from 0.10 to 12.5 micrograms/ml and that of S . marcescens, from 0.2 to 25 micrograms/ml . The growth of 80.8% of P . aeruginosa was inhibited at the concentration of 12.5 micrograms/ml . The distribution of E . cloacae ranged from 0.1 to 50 micrograms/ml . For pharmacokinetic study, SBT/CPZ was given in a single dose of 20 mg/kg by drip infusion for 1 hour in 2 children and 40 mg/kg by drip infusion for 1 hour in 1 children . With drip infusion of SBT/CPZ, the peak serum level were 17.8/43.9 micrograms/ml, 21.8/75.5 micrograms/ml on completion of the infusion, respectively . SBT/CPZ was effective in 14 cases out of 16 cases with clinical effect . No side effect was observed except for eosinophilia in 1 case.

Med J Aust, 1984 Sep 29, 141(7), 437 - 42
Cephalosporin antibiotic agents; Kemp R; The cephalosporins are a group of antibiotic agents that have been available now for 20 years . Three classes, or generations, of cephalosporins are recognized . The newer third-generation drugs have wider spectra of antibacterial activity; because of this attribute and their ability to achieve high bactericidal titres in CSF these newer compounds constitute an advance in antibiotic therapy by providing safe and effective treatment for Gram-negative bacillary meningitis . The earlier cephalosporins provide cheap, useful and convenient prophylaxis for vascular and orthopaedic operations near the inguinal area . Comparative trials with other broad-spectrum agents need to be performed before the true place of the third-generation agents in anti-infective therapy and prophylaxis is finally determined.

JPEN J Parenter Enteral Nutr, 1984 Sep-Oct, 8(5), 501 - 5
A prospective randomized trial of central venous catheter removal versus intravenous amphotericin B in febrile neutropenic patients; Lazarus HM et al.; Empiric amphotericin B therapy was compared to central venous catheter Githdrawal in a prospective randomized trial . Of 32 febrile, neutropenic patients with indwelling Broviac catheters and without documented infection, 14 had persistent fever while receiving broad spectrum antibacterial drugs . Six patients were randomized to catheter removal and eight patients received amphotericin B empirically . None of six patients responded to catheter removal and six of eight defervesced after receiving antifungal therapy (p less than 0.01) . Of the six patients in whom catheters were removed, two later became afebrile while on subsequent therapy with amphotericin B . Culture and histologic evaluation of the removed catheters failed to implicate the prosthesis as an infectious source . Central venous catheters in a persistently febrile neutropenic host need not be removed, unless local difficulties or bacteremia with skin commensal organisms occur . Amphotericin B can be infused through a central venous catheter in febrile, neutropenic patients unresponsive to empiric antibacterial drugs, with many patients becoming afebrile as a result of this therapy.

Antimicrob Agents Chemother, 1984 Sep, 26(3), 414 - 6
Protection by D-amino acids against growth inhibition and lysis caused by beta-lactam antibiotics; Tuomanen E et al.; D-Isomers of several amino acids completely protected growing cultures of Escherichia coli against all antibacterial effects of beta-lactam antibiotics up to approximately two to three times the MICs of the antibiotics . L-Isomers of amino acids were ineffective . Protection depended on the concentration and time of addition of the D-amino acids . This appears to be the first demonstration of natural products capable of reversing the antibacterial effects of beta-lactam antibiotics.

Pharmazie, 1984 Sep, 39(9), 621 - 5
{The use of preservatives in skin preparations}; Van Ooteghem M; Dermatological preparations may be contaminated during their manufacture and their use . On account of the danger of this contamination, different Pharmacopoeia prescribe the maximal allowable number of microorganisms in the different dermatological preparations . The preservatives used must kill or diminish their number in a period of time equal to the time elapsed between two applications . This time however could be different for each preparation . Therefore the preservatives must have antibacterial activities adapted to the use of the dermatological preparation . The activity can be given by the D-value or the decimal reductiontime . The D-values of the different kinds of dermatological preparations have been calculated with a startcontamination of 10(6) microorganism g . The activity of a preservative must be determined directly in the preparation . Firstly the preparation with a preservative is contaminated with microorganisms, secondly the killing rate is determined and finally the D-value is calculated . After the calculation of the D-value of different samples each containing a different preservative and several concentrations, it is possible to select a preservative and to determine his concentration giving a D-value corresponding to the D-value required by the use of the dermatological preparation.

Am J Hosp Pharm, 1984 Sep, 41(9), 1802 - 6
Stability of cytarabine, methotrexate sodium, and hydrocortisone sodium succinate admixtures; Cheung YW et al.; A high-performance liquid chromatographic (HPLC) method was developed for simultaneous determination of cytarabine, methotrexate sodium, and hydrocortisone sodium succinate, and the stability of the three drugs mixed together in four infusion fluids was assessed . Solutions were prepared with two concentrations of the three drugs similar to those administered intrathecally . Admixtures were prepared in Elliott's B solution, 0.9% sodium chloride injection, 5% dextrose injection, and lactated Ringer's injection . and lactated Ringer's injection . Solutions were filtered and kept in a disposable syringe in a 25 degrees C water bath for 24 hours . An HPLC assay capable of separating the three drugs and their degradation products was developed and validated . With one exception, all three drugs were stable in all four solutions for 24 hours . Hydrocortisone sodium succinate concentrations decreased to less than 90% of initial concentration in one of the admixtures with Elliott's B solution . No precipitation was noted in any admixture during the first eight hours of storage, but longer storage led to precipitation of unknown substances in some solutions . Admixtures of these three drugs in the four solutions tested are stable for at least 10 hours at 25 degrees C . However, intrathecal and administration of such admixtures within several hours of preparation is encouraged since none contains antibacterial preservatives.

J Med Chem, 1984 Sep, 27(9), 1225 - 9
Synthesis and antibacterial activity of 2-{(methoxycarbonyl)methylene}cephalosporins; Kim CU et al.; The synthesis and in vitro activities of a series of 2-{(methoxycarbonyl)methylene}-3-cephem-4-carboxylic acids with methyl or acetoxymethyl at the 3-position are described . The key step in the synthesis includes the stereospecific formation of the 2-{(Z)-(methoxycarbonyl)methylene} group by Pummerer rearrangement of the sulfoxides 3a and 3b . It was also possible to isomerize photochemically the C-2 olefin of 4a to its E isomer, 9 . The new derivatives exhibited significant in vitro Gram-positive antibacterial activity.

Infect Immun, 1984 Sep, 45(3), 692 - 6
Effect of zinc and phosphate on an antibacterial peptide isolated from lung lavage; LaForce FM et al.; Incubation of Escherichia coli (10(4) organisms per ml) in cell-free rabbit lung lavage for 30 min at 37 degrees C resulted in a 70% reduction in colony counts on deoxycholate agar . A low-molecular-weight peptide (about 3,400 daltons), with zinc as a cofactor, was responsible for this activity . The peptide was isolated by Sephadex G-15 separation of lyophilized rabbit lung lavage which had been centrifuged to remove macrophages and suspended phospholipids and passed through a 10,000-dalton (pore size) membrane filter . Peptide activity against E . coli was inhibited by phosphate buffer but not by borate, Tris, or barbital buffer . Bacteria incubated in phosphate buffer and then washed in saline were resistant to peptide activity . Antibacterial activity was also inhibited when peptide-exposed bacteria were incubated in phosphate buffer before deoxycholate treatment . 32P-radiolabeled E . coli cells lost about 20% of their radiolabel after 15 min of incubation with peptide.

Acta Anaesthesiol Belg, 1984 Sep, 35(3), 237 - 41
Air embolism due to the Mayfield skull clamp; De Lange JJ et al.; During posterior craniotomy of a 77 years old man in the sitting position air embolism was monitored and reoccurred not withstanding proper measures . Only at the end of the operation the source was discovered: when the head was removed from the Mayfield skull clamp the embolism reoccurred once more . All this not withstanding the meticulous treatment of the three points of the head holder with antibacterial ointment, in the beginning.

Proc Natl Acad Sci U S A, 1984 Sep, 81(18), 5841 - 4
Somatic mutation of the T15 heavy chain gives rise to an antibody with autoantibody specificity; Diamond B et al.; The S107 IgA kappa-chain myeloma cell line makes an antiphosphocholine antibody of the T15 idiotype . A somatic mutant of this line, U4, makes an immunoglobulin with a single amino acid substitution of an alanine for a glutamic acid at residue 35 . This single amino acid change results in a loss of phosphocholine binding activity . However, the U4 immunoglobulin has acquired reactivity with a variety of phosphorylated macromolecules, including double-stranded DNA, protamine, and cardiolipin . Thus, a single amino acid change in the T15 heavy chain can transform an antibacterial antibody into an antibody that resembles the autoantibodies seen in mice and man with autoimmune disease.

J Gen Microbiol, 1984 Sep, 130 ( Pt 9), 2253 - 65
Transport and hydrolysis of antibacterial peptide analogues in Escherichia coli: backbone-modified aminoxy peptides; Payne JW et al.; Aminoxy analogues of di- and tripeptides in which the peptide linkage is replaced by -CO-NHO-, either as an L- or D-2-aminoxypropionic acid (L or D-OAla) residue, have been examined for antibacterial activity in vitro and for uptake into Escherichia coli . Isolation of analogue-resistant mutants and cross-resistance tests with peptide-transport mutants indicate that all three peptide permeases can transport these backbone-modified analogues . A number of mutants with defects in particular intracellular peptidases show decreased sensitivity to a range of these analogues, allowing identification of the enzymes responsible for their cleavage and confirming that hydrolysis is essential for their toxicity . Ala-OAla is a bacteriostatic agent that inhibits nucleic acid and protein synthesis within 1 min of being added to an exponentially growing culture . In crude extracts Ala-OAla inhibits transaminase activity but only after liberation of OAla by endogenous peptidases . These antibacterial agents illustrate an approach to drug targeting in which peptide carriers are used to promote uptake of essentially impermeant toxic moieties.

Laryngoscope, 1984 Sep, 94(9), 1198 - 217
Actinomycosis: diagnostic and therapeutic considerations and a review of 32 cases; Bennhoff DF; Actinomycosis was at one time a common diagnosis in this country . It still is fairly common in some parts of the world . As the numbers of antibiotics and indications for their use have increased, the disease has almost become a medical rarity in the United States . This fact might be thought a paradox in view of the universal presence of the actinomyces organisms in every human mouth . However, it is perhaps not well recognized that the actinomyces are true bacteria, and that they are particularly sensitive to most of the common antibacterials in current usage . These facts have combined to decrease the clinical frequency of the disease as well as effectively reduce the opportunity for securing a satisfactory specimen for laboratory culture in suspected cases . Actinomycosis can present in a variety of forms and may mimic other infections or even neoplasms . The clinical pattern of remission and exacerbation of symptoms occurring in parallel sequence with initiation and cessation of antibiotic administration is a phenomenon which should increase suspicion for actinomycosis in any of its manifestations.

J Med Chem, 1984 Sep, 27(9), 1103 - 8
Novel amino-substituted 3-quinolinecarboxylic acid antibacterial agents: synthesis and structure-activity relationships; Wentland MP et al.; A series of novel 3-quinolinecarboxylic acid derivatives have been prepared and their antibacterial activity evaluated . These derivatives are characterized by fluorine attached to the 6-position and substituted amino groups appended to the 1- and 7-positions . Structure-activity relationship studies indicate that antibacterial potency is greatest when the 1-substituent is methylamino and the 7-substituent is either 4-methyl-1-piperazinyl, 16, or 1-piperazinyl, 21 . Derivatives 16 and 21, the 1-methylamino analogues of pefloxacin and norfloxacin, respectively, show comparable in vitro and in vivo antibacterial potency to these two known agents . The activity (vs . Escherichia coli Vogel) of 16 (amifloxacin) is the following: in vitro MIC (microgram/mL) = 0.25; in vivo (mice) PD50 (mg/kg) = 1.0 (po), 0.6 (sc).

J Hosp Infect, 1984 Sep, 5(3), 323 - 8
A comparison of the in-vitro antibacterial and complement activating effect of 'OpSite' and 'Tegaderm' dressings; Holland KT et al.; Two readily available semipermeable polyurethane dressings, 'OpSite' and 'Tegaderm', were tested for their in vitro ability to kill potential bacterial pathogens and activate complement C3 . In bacterial killing tests, 'OpSite' was superior to 'Tegaderm' and in addition only 'OpSite' activated C3 . It is concluded that in the practical situation, 'OpSite' could well confer a greater margin of safety.

J Antimicrob Chemother, 1984 Sep, 14 Suppl B, 45 - 51
The action of beta-lactamases on desacetyl-cefotaxime and cefotaxime; Labia R et al.; Desacetyl-cefotaxime is the main cefotaxime metabolite . Its antibacterial activity is less than that of the parent molecule, but the combination of cefotaxime and desacetyl-cefotaxime is often synergistic . We analysed the hydrolysis of desacetyl-cefotaxime, in comparison with cefotaxime, by 10 beta-lactamases, mostly cephalosporinases, isolated from various Gram-negative species . From partially purified beta-lactamase preparations of high specific activity, we determined the maximum rates of hydrolysis (Vm) and the Michaelis constants (Ki and Km when possible) . It appeared for 7 beta-lactamases the rate of desacetyl-cefotaxime hydrolysis was 2.1 times greater than that of cefotaxime, in terms of geometrical mean value, but with 3 enzymes no hydrolysis was shown for one compound . For 8 enzymes, the Ki, and sometimes Km, of desacetyl cefotaxime are 39 times higher than those of cefotaxime (geometric mean value), which corresponds to a lower affinity.

Can J Microbiol, 1984 Aug, 30(8), 1068 - 72
The antibacterial activity of some naturally occurring 2,5-dihydroxy-1,4-benzoquinones; Brewer D et al.; Polyporic acid, atromentin, bovinone, and oosporein are common metabolic products of a number of species of fungi . The related compound cochliodinol and its congeners are produced by several Chaetomium spp . These quinonoid metabolites have been shown to inhibit the growth and metabolism of a range of bacterial genera . The antibiotic activity of the quinones depends on the substituents at the 3 and 6 positions of the 2,5-dihydroxy-1,4-benzoquinone ring; in aerobic systems the activity appears to be inversely proportional to the polarity of the metabolite . It has been shown that reduction of the quinone to the hydroquinone changes the antibiotic activity of these metabolites but does not abolish it . Contrary to previous reports, the activity of these hydroquinones is not reversed by cysteine.

J Appl Bacteriol, 1984 Aug, 57(1), 179 - 81
A note on the effect of dilution and temperature on the bactericidal activity of potassium sorbate; Lusher P et al.; The effect of dilution and temperature on the antibacterial properties of potassium sorbate was determined . The time taken to kill a standard inoculum of Escherichia coli was increased considerably after either dilution of the preservative or lowering of the temperature . The value for the concentration exponent, eta, was approximately 3 and that for the temperature coefficient, Q10, was 2.3.

Fundam Appl Toxicol, 1984 Aug, 4(4), 558 - 67
Comparative nephrotoxicity of hydroxygentamicin and other aminoglycosides in rats; Slighter RG et al.; The nephrotoxicity of hydroxygentamicin and amikacin was examined in young adult Fischer 344 rats . Serum creatinine (SCr) and urea nitrogen (BUN) levels were not significantly affected following sc injection of 80 or 160 mg/kg/day of hydroxygentamicin for 15 days . However, 250 mg/kg of amikacin produced significant increases in both parameters and in kidney/body weight ratios . The ratios were also significantly increased after 80 or 160 mg/kg of hydroxygentamicin, but kidneys of rats receiving amikacin were considerably heavier than those of rats treated with hydroxygentamicin . The antibacterial potency of 250 mg/kg of amikacin is comparable to that of 100 mg/kg of hydroxygentamicin . Additional studies, directly comparing hydroxygentamicin, a mutational biosynthetic, with gentamicin or netilmicin, all at 40, 80, and 160 mg base/kg, and incorporating renal function parameters as well as SCr, BUN, organ weight, tissue concentration, and kidney histopathology, revealed a characteristic pattern typical of aminoglycoside nephrotoxicity in mature adult male rats . In most parameters, values in rats given hydroxygentamicin or netilmicin were normal and comparable to those in controls, but kidney/body weight ratios were significantly increased at high doses . However, kidneys of rats medicated with gentamicin at comparable doses were considerably heavier than those of hydroxygentamicin-treated rats . Significant nephrotoxicity also was seen in rats given low doses of gentamicin or netilmicin . Eosinophilic granulation and vacuolization of renal proximal tubular epithelium, interstitial inflammation, and tubular dilation were observed microscopically with all three drugs in the following descending order of severity: gentamicin greater than netilmicin greater than hydroxygentamicin . The effects on proximal tubular epithelial cells following treatment with amikacin, netilmicin, or hydroxygentamicin correlated reasonably well with renal drug concentrations, but drug concentrations of gentamicin, which produced the most extensive kidney injury, were lower than those of the other three aminoglycosides . Elevated SCr or BUN were indicative of the presence of nephrosis, but early stages of tubular epithelial degeneration were not predicted by increases in BUN or SCr . Although minimal or mild nephrosis was seldom predicted by polyuria, proteinuria, or changes in osmolality, effects observed in renal function parameters usually correlated well with renal histopathology . However, a decrease in osmolality correlated best with enlarged kidneys and changes in renal morphology.

Biull Eksp Biol Med, 1984 Aug, 98(8), 168 - 72
{Action of low-frequency ultrasound on the peritoneum, peritoneal exudate cells and the course of experimental peritonitis}; Paukov VS et al.; The authors studied the action of low-frequency ultrasound on rat and guinea-pig peritoneal exudate cells during aseptic peritonitis, on the intact peritoneum of these animals, and on experimental peritonitis in guinea-pigs . It was shown that ultrasound "hammers in" India ink solutions and antibacterial drugs into the peritoneum and in combination with antibiotics, it increases the guinea-pig survival rate in peritonitis . Ultrasound was not found to produce a direct bactericidal effect in vivo . Exposure of peritoneal exudate to ultrasound (1 s/cm2) demonstrated an increase in chemotaxis of neutrophil leukocytes to autologic serum and appreciable phagocytic activity . A longer exposure (up to 3-5 s/cm2 or 6-8 s/cm2) resulted in the partial damage to the peritoneum . Leukocytes, mesotheliocytes and subperitoneal striated muscles were found to be especially sensitive to ultrasound.

J Appl Bacteriol, 1984 Aug, 57(1), 69 - 74
Production and properties of a bacteriocin from Myxococcus coralloides D; Munoz J et al.; Myxococcus coralloides D was found to produce a substance with a narrow range of antibacterial activity . This substance was produced during the exponential growth phase and was not inducible by ultraviolet light or mitomycin C treatment . The bacteriocin was precipitable by ammonium sulphate, and showed resistance to heat (100 degrees C for 10 min), trypsin, lysozyme, beta-glucuronidase, DNase, RNase, acetone, ethyl ether, urea and mercaptoethanol; it was partially destroyed by pronase and inactivated at extreme pH values . Electron microscopy did not reveal any phage-like particles associated with bacteriocin activity.

Chemioterapia, 1984 Aug, 3(4), 250 - 4
Comparative activity of ceftazidime and four other cephalosporins against gram-negative bacteria and their sensitivity to beta-lactamases; Galante D et al.; The in vitro activity of ceftazidime compared with other beta-lactamase stable compounds was assessed against recent Gram-negative isolates . Three hundred forty-three bacterial strains were isolated from patients affected with UTI, identified by standard bacteriological methods and investigated for their production of beta-lactamases by the Nitrocefin test . MICs and MBCs (minimum inhibitory concentrations and minimum bactericidal concentration) of ceftazidime, cefamandole, cefoxitin, cefotaxime and cefuroxime were determined by a miniaturized dilution broth method against all beta-lactamase producing bacteria (129 out of 343) . Sensitivity of the antibiotics to beta-lactamases isolated and semipurified by ultrasonic disruption and high-speed centrifugation was assessed by a spectrophotometric method . The in vitro antibacterial activity of each antibiotic was correlated to its sensitivity to isolated beta-lactamases . Ceftazidime showed lower MIC and MBC values and lower MBC/MIC ratios than the other compounds against all the bacteria including Pseudomonas spp . In addition, ceftazidime was not hydrolyzed significantly by any isolated beta-lactamases.

Antimicrob Agents Chemother, 1984 Aug, 26(2), 139 - 44
New polymeric biocides: synthesis and antibacterial activities of polycations with pendant biguanide groups; Ikeda T et al.; Acrylate monomers with pendant biguanide groups were successfully synthesized, and their homopolymers and copolymers were prepared with acrylamide . These cationic disinfectants of polymeric forms exhibited high antibacterial activity against gram-positive bacteria, whereas they were less active against gram-negative bacteria . It was found that the activity of the polymeric disinfectants was much higher than that of the monomeric species, and the difference in activity between the polymers and the monomers was discussed on the basis of their contributions to each elementary process of the lethal action.

Antimicrob Agents Chemother, 1984 Aug, 26(2), 136 - 8
Empirical antibacterial therapy in febrile, granulocytopenic bone marrow transplant patients; Peterson PK et al.; Fifty febrile, granulocytopenic allogeneic bone marrow transplant patients receiving prophylactic trimethoprim-sulfamethoxazole were randomized to one of two empirical antibiotic regimens to determine whether a shortened course of empirical therapy was beneficial . Of the 50 patients, 25 received empirical tobramycin and ticarcillin for only 3 days, and 25 were maintained on empirical tobramycin and ticarcillin until they were afebrile and no longer granulocytopenic . Although the incidence of bacterial infections in the two groups was not statistically significantly different, almost twice as many bacterial infections were observed in the group that received the short course of empirical therapy . Furthermore, because of the high incidence of bacterial infection and clinical concerns about occult bacterial sepsis, within 2 weeks of the randomization the overall use of parenteral antibacterial agents was similar in both groups . The incidence of invasive fungal disease and the use of amphotericin B therapy were similar in both groups . The results of this study suggest that little clinical benefit is likely to be seen in bone marrow transplant patients treated with short-course empirical tobramycin and ticarcillin, despite the administration of prophylactic trimethoprim-sulfamethoxazole, and emphasize the need for new strategies to prevent infections with gram-positive and trimethoprim-sulfamethoxazole-resistant gram-negative bacteria in these patients.

Antibiotiki, 1984 Aug, 29(8), 595 - 600
{Effect of Streptomyces spheroides proteinases on the mechanism of antibacterial protection in an experiment}; Egorov NS et al.; The effect of Streptomyces spheroides proteinases on the process and character of the local reaction to intraperitoneal infection of mice with E . coli was studied experimentally . It was shown that administration of the proteinases promoted a decrease in the dissemination of the abdominal cavity and a more rapid elimination of the microorganisms from the infection foci . The proteinases potentiated the macrophagal component of the local reaction by accelerating migration of the macrophages and increasing their phagocytic activity and the activity of the lysosomal enzymes . Proteinases gave rise to a pronounced activation of the neutrophils, an increase in the phagocytic capacity of the young forms and a change in intracellular enzymes . It was demonstrated that proteinases changed interrelation between the cell elements in the infection foci, the character of interaction of the quantitative and functional parameters of the local reaction and interrelationship between the phagocytic activity and the enzymatic balance of the cells . They increased the effect of the macrophages on migration and the functional state of the neutrophiles.

J Med Chem, 1984 Aug, 27(8), 947 - 53
Preparation and antibacterial activities of new 1,2,3-diazaborine derivatives and analogues; Grassberger MA et al.; 1,2-Dihydro-1-hydroxy-2-(organosulfonyl)areno{d} {1,2,3}diazaborines 2 (arene = benzene, naphthalene, thiophene, furan, pyrrole) were synthesized by reaction of (organosulfonyl)hydrazones of arene aldehydes or ketones with tribromoborane in the presence of ferric chloride . The activities of 2 against bacteria in vitro and in vivo (Escherichia coli) were determined and structure-activity relationships are discussed . Included in this study are 2,3-dihydro-1-hydroxy-2-(p-tolylsulfonyl)-1H-2,1-benzazaborole+ ++ (3) and 1-hydroxy-1,2,3,4-tetrahydro-2-(p-tolylsulfonyl)-2,1-benzazabor ine (4) as well as the carbacyclic benzodiazaborine analogue 4-hydroxy-3-(p-tolylsulfonyl)isoquinoline (7) . The nature of the active species is briefly discussed.

Eur J Clin Microbiol, 1984 Aug, 3(4), 347 - 50
Mutational resistance to 4-quinolone antibacterial agents; Smith JT; The activity of ten 4-quinolone drugs was tested against five Escherichia coli mutants . Mutational resistance was found to reduce the activity of all ten drugs, indicating that they display biochemical cross-resistance with each other . However, ciprofloxacin and, to a lesser extent, ofloxacin and norfloxacin were so highly active that the most resistance exhibited by any mutant fell well within the serum drug concentration ranges attainable in humans . Hence, clinical cross-resistance in Escherichia coli at least, need not necessarily apply to such highly active 4-quinolone antibacterial agents.

Plast Reconstr Surg, 1984 Aug, 74(2), 269 - 73
Rhinophyma: treatment with electrocautery and silver-impregnated porcine xenograft; Ersek RA et al.; A typical case of advanced rhinophyma is reported . Partial excision reduced the size of the nose by two-thirds, leaving a thin layer of dermis . This was covered with silver-impregnated porcine xenograft, which allowed efficient drainage and remained adherent in its initial application for 2 weeks . A total of four applications of silver-impregnated porcine xenografts--the last two involving only very small areas--were required for complete epithelialization at 5 weeks after surgery . We believe that this xenograft is an ideal dressing for wounds resulting from partial excision of rhinophymatous tissue, providing the beneficial effects of biological dressings, including the hemostatic effects of collagen with the added benefit of silver's potent antibacterial properties . Silver-impregnated porcine xenograft reduces patient discomfort and results in rapid healing with excellent cosmetic results.

J Gen Microbiol, 1984 Aug, 130 ( Pt 8), 1999 - 2005
The antibacterial action of Tinopal AN; Phillips MK et al.; The bactericidal activity of Tinopal AN {1,1-bis(3,N-5-dimethyl-benzoxazol-2-yl)-methine p-toluene sulphonate} was shown to be due to a mechanism entirely independent of its inhibitory effects upon NADH dehydrogenase which were reported previously . Whereas the compound had no significant effect upon DNA synthesis in Escherichia coli D22, RNA and protein synthesis were immediately and markedly inhibited . In confirmation, Tinopal AN caused an immediate cessation in inducible beta-galactosidase synthesis in the same organism . An in vitro assay of the transcription of calf-thymus DNA by purified E . coli RNA polymerase showed that this process was inhibited by Tinopal AN.

Arch Intern Med, 1984 Aug, 144(8), 1562 - 8
Infection prophylaxis in acute leukemia . Comparative effectiveness of sulfamethoxazole and trimethoprim, ketoconazole, and a combination of the two; Estey E et al.; In a comparative study of infection prophylaxis, patients with acute leukemia receiving remission induction therapy were assigned either no prophylaxis, sulfamethoxazole and trimethoprim, ketoconazole, or the combination of sulfamethoxazole and trimethoprim and ketoconazole . Both sulfamethoxazole and trimethoprim and the combination of sulfamethoxazole and trimethoprim and ketoconazole substantially reduced the overall incidence of infection consequent to a marked decrease in bacterial infection . However, sulfamethoxazole and trimethoprim were associated with an increased rate of fungal infection, while ketoconazole decreased this complication . No form of prophylaxis reduced infectious mortality or increased the complete remission rate . However, because of its effect in reducing infectious morbidity, we conclude that patients with acute leukemia receiving remission induction treatment should be given antibacterial and antifungal prophylaxis.

J Antibiot (Tokyo), 1984 Jul, 37(7), 700 - 5
Takaokamycin, a new peptide antibiotic produced by Streptomyces sp; Omura S et al.; A new peptide antibiotic named takaokamycin was isolated from a fermentation broth of Streptomyces sp . AC-1978, a soil isolate . It exhibits antibacterial activity against some Gram-positive bacteria . The molecular weight was found to be 1,130 on the basis of elemental analysis, FD-mass spectrum and 1H and 13C NMR . Acid hydrolysate of takaokamycin contains isoleucine, threonine and unidentified amino acids.

Jpn J Antibiot, 1984 Jul, 37(7), 1289 - 93
{Antibiotic sensitivity of Branhamella catarrhalis isolated from respiratory tract infections}; Nishioka K et al.; The efficacy of antibiotics including some newly developed penicillins and cephems on clinically isolated Branhamella catarrhalis was evaluated in vitro . Among 44 strains of B . catarrhalis which were isolated from expectorated sputum of patients with respiratory tract infections 36 strains were proved to produce beta-lactamase . MICs of penicillins for beta-lactamase positive strains ranged from less than or equal to 0.05 to 3.13 micrograms/ml, while those for beta-lactamase negative strains were all less than 0.05 microgram/ml . MICs of cephems, on the other hand, ranged more variably, especially among beta-lactamase positive strains . The most effective cephem we tested was LMOX which could inhibit all the strains of B . catarrhalis at the concentration of 0.05 microgram/ml or less . Aminoglycosides as well as macrolides also showed sufficiently low MIC values . We therefore concluded that the confirmation of beta-lactamase production by B . catarrhalis seems to be indispensable for the determination of an antibacterial activity of beta-lactam antibiotics.

Arch Gerontol Geriatr, 1984 Jul, 3(2), 175 - 88
Antibody and immunoglobulin levels in aged humans; Batory G et al.; IgM and IgG type antibody titers and levels of serum IgG, IgA and IgM were determined in healthy young and aged subjects . The proportion of subjects of low antibacterial agglutinin titers progressively increased during the 7th and 8th decades of life . Anti-streptolysin-O titers were also shifted to the lower values in aged subjects, at least until the 8th decade of life, although subnormal values compared to the young control range were less frequent than in the case of IgM type antibodies . Anti-streptokinase values did not seem affected by age . In contrast to antibody levels, serum IgM was similar or slightly higher in old compared to young subjects . Evidence is presented that the proportion of 7 S IgM drops with aging . Both IgA and IgG levels increased through the 7th, 8th and 9th decades of life . Different class immunoglobulin levels seemed to be considerably correlated and a tendency to correlate was found between IgG type antibody and serum IgG levels . Complex investigations including quantitation of antibodies to extrinsic and intrinsic antigens and serum immunoglobulins are proposed to define the humoral immune status of aged subjects and to understand the causes as well as the diagnostic and prognostic significance of old age 'imbalances'.

J Antibiot (Tokyo), 1984 Jul, 37(7), 750 - 9
Chemical modification of spiramycins . III . Synthesis and antibacterial activities of 4''-sulfonates and 4''-alkylethers of spiramycin I; Sano H et al.; Among the derivatives protected with t-butyldimethylsilylether of spiramycin I, 2'-O-acetylspiramycin I 3,18-(O-t-butyldimethylsilyl)acetal was found to be a suitable intermediate for 4''-modification of spiramycin I . Seven 4''-sulfonates and four 4''-alkylethers were synthesized, which were more active against bacteria in vitro than spiramycin I . 4''-Substituted derivatives with relatively small sulfonyl and alkyl groups were comparable in therapeutic effect to spiramycin I.

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