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R factors conferring a high level of resistance to trimethoprim have been identified in one strain of Escherichia coli and one of Klebsiella aerogenes, both isolated from infected urines.

Kalafungin is a new antimicrobial agent obtained from the culture broth of a soil isolate of Streptomyces tanashiensis , designated Streptomyces tanashiensis strain Kala UC-5063. Kalafungin is a chemically stable, nonpolyene agent which is ex-extremely inhibitory in vitro against a variety of pathogenic fungi, yeasts, protozoa, gram-positive bacteria, and, to a lesser extent, gram-negative bacteria.

A total of 1,268 patients admitted to hospital wards were kept under surveillance by one observer throughout their stay in hospital. All drugs given to them and the occurrence of adverse reactions were recorded.Drug reactions were found in 10.2% of the 1,160 patients who received drug therapy. Most reactions were due to known pharmacological actions of the drugs. Though only four reactions were of life-threatening seriousness, 80% of the 129 reactions observed were of moderate severity. Digitalis preparations, bronchodilator drugs, and ampicillin had the highest reaction rates. It is suggested that larger surveys of adverse reactions in relation to drug usage would make a useful contribution to the problem.

Melinacidin is a crystalline mixture of closely related antibacterial agents produced by Acrostalagmus cinnabarinus var. melinacidinus. Melinacidin inhibits a variety of Gram-positive bacteria in vitro but is found to be toxic and ineffective in the treatment of experimental bacterial infections in mice. Melinacidin which inhibits the growth of KB and L-1210 cells in tissue culture appears to belong to the "3, 6-epidithiadiketopiperazine" group of antibiotics.

In Escherichia coli K-12, the conversion of glycerol to triose phosphate is regulated by two types of control mechanism: the rate of synthesis of glycerol kinase and the feedback inhibition of its activity by fructose-1,6-diphosphate. A strain which has lost both control mechanisms by successive mutations, resulting in the constitutive synthesis of a glycerol kinase no longer sensitive to feedback inhibition, can produce a bactericidal factor from glycerol. This toxic factor has been identified by chemical and enzymological tests as methylglyoxal. Methylglyoxal can be derived from dihydroxyacetone phosphate through the action of an enzyme which is present at high constitutive levels in the extracts of the mutant as well as that of the wild-type strain. Nine spontaneous mutants resistant to 1 mm exogenous methylglyoxal have been isolated. In all cases the resistance is associated with increased levels of a glutathione-dependent enzymatic activity for the removal of methylglyoxal. Methylglyoxal-resistant mutants derived from the glycerol-sensitive parental strain also became immune to glycerol.

Acute epiglottitis is a fulminating infection of young children, requiring urgent and specific treatment. Most cases are caused by infection with Haemophilus influenzae type b. Only a few cases, nearly all of them fatal, have been reported from Britain, but probably many others go unrecognized. Of four cases seen by us in the past six years three survived, having responded rapidly and completely to treatment. This consisted chiefly of measures to deal with respiratory tract obstruction and parenteral administration of antibiotics. There is need for a widespread awareness of the existence, presenting features, and extreme urgency for treatment of this disease.

A case of agranulocytosis is reported in which amodiaquine, to which the patient had been exposed, was found to be toxic to the patient's bone marrow cells when these were cultured in an agar colony system in vitro. This technique should be investigated in other patients with agranulocytosis as a possible means of detecting toxic agents.

In a survey of adverse drug reactions in wards of two Belfast hospitals for 52 weeks in 1965–6, 2·9% of 1,268 patients seen were admitted to hospital because of adverse reactions to drugs taken for therapeutic reasons and 2·1% were admitted because of self-poisoning. Patients admitted because of adverse drug reactions were older than those admitted because of self-poisoning and stayed in hospital longer. Among the drugs which caused the adverse reactions were digitalis preparations, antibiotics, corticosteroids, anticoagulants, analgesics, and tranquillizers. Hypersensitivity and side-effect types of reactions were the most common. Barbiturates were the most frequently used drugs in suicidal attempts.

An analytical procedure was devised which can distinguish members of the streptothricin family of antibiotics. It is based upon an analysis of the hydrolysis products of the antibiotics using a Technicon amino acid autoanalyzer under special conditions. The various fragments including the different streptolidine-amino sugar compounds were well resolved. A basic water-soluble antibiotic discovered in our laboratories and named LL-BL136 was compared to other members of this group by this technique. It was not differentiated from the antibiotic SF-701 reported by Tsuruoka. The autoanalyzer results along with other physicochemical data permitted a structure proposal for this antibiotic, which is the N -methyl-desformimino derivative of antibiotic LL-AC541.

Ferrous sulphate administered together with tetracycline and three of its derivatives-oxytetracycline, methacycline, and doxycycline-was found seriously to impair the absorption of these antibiotics. Thus even small doses of iron taken simultaneously should be avoided during tetracycline treatment.

We are indebted to the following for help with this work: Dr. K. Fantes (Glaxo Group Limited) for adsorbing rhinoviruses on to aluminium phosphate gel ; Dr. F. Himmelweit for supplying Drakeol-Arlacel ; Mr. P. D. McHugh and Miss A. Maclntyre (Pfizer Ltd.) for carrying out neutralization tests on volunteers given Pfizer H.G.P. vaccine ; Dr. M. L. Bynoe and Miss E. Bullock (Common Cold Research Unit) for clinical observations ; and technicians for their excellent assistance. We would also like to thank volunteers at the Common Cold Research Unit, at the Micro biological Research Establishment, Port?n, and at Salisbury Theo logical College, and the general practitioners who administered vaccine. REFERENCES Andrewes, C. H. (1948). J. roy. Soc. Arts, 96, 200. Buckland, F. E., Doggett, J. E., and Tyrrell, D. A. J. (1964) J. Hyg, (Lond.), 62, 115. and Tyrrell, D. A. J. (1965). Ibid. In press. Bynoe, M. L., Hobson, D., Horner, J., Kipps, A., Schild, G. C, and Tyrrell, D. A. J. (1961). Lancet, 1 1194. Doggett, J. E., Bynoe, M. L., and Tyrrell, D. A. J. (1963). Brit. med. J., 1, 34. Fantes, K. H. (1962). J. Hyg. (Lond.), 60, 123. Hamre, D., and Procknow, J. J. (1963). Amer. Rev. resp. Dis., 88, Part 2, p. 277. Hayflick, L., and Moorhead. P. S. (1961). Exp. Cell. Res., 25, 585. Himmelweit, F. (1960). Brtt. med. J., 2, 1690. Mogabgab, W. J. (1962). Amer. J. Hyg., 76, 15. Mufson, M. A., Ludwig, W. M., James, H. D., Gauld, L. W., Rourke, J. A., Holper, J. C, and Chanock R. M. (1963). J. Amer, med* Ass., 186, 578. Price, W. H. (1957). Proc. nat. Acad. Sei. (Wash.), 43, 790. Taylor-Robinson, D. (1963). Arch. ges. Virusforsch., 13, 281. and Tyrrell, D. A. J. (1962). Brit. J. exp. Path., 43, 264. Tyrrell, D. A. J., Bynoe, M. L., Buckland, F. E., and Hayflick, L. (1962X Lancet, 2, 320. and Parsons, R. (1960). Ibid., 1, 239.

Scopafungin is the major component of the non-polyenic endomycin complex which was extracted from Streptomyces hygroscopicus var. enhygrus var. nova and purified by partition column chromatography or silica gel column chromatography followed by crystallization. It is a white crystalline compound which contains carbon (60.95%), hydrogen (9.00%), nitrogen (4.01%) and oxygen (26.46%) and melts at 119.3°C. In methanol, 0.1N HCl in methanol, and 0.1N KOH in methanol, it exhibits maximum UV absorption at 231nm and is dextrorotatory in dimethylformamide, [α]25D+20. Titration in glacial acetic acid indicates an equivalent weight of 1268. Scopafungin is soluble in lower alcohols, glacial acetic acid, acetone - water (3:2) and water-saturated 1-butanol, but is insoluble in water, acetone, ethyl acetate, methyl ethyl ketone, methylene chloride, chloroform, butanol or ether.

Recent literature on the antibiotics enduracidin, moenomycin, prasinomycin, and 11.837 RP suggested an interaction with murein synthesis. Incubation of sensitive strains from Bacillus cereus and Staphylococcus aureus in a “wall medium” containing labeled l -alanine showed that all four antibiotics inhibited the incorporation of alanine into murein and gave rise to accumulation of radioactive uridine diphosphate- N -acetyl-muramyl (UDP-MurNAc)-pentapeptide. Peptidoglycan was synthesized when the particulate enzyme of B. stearothermophilus was incubated with the murein precursors UDP- N -acetyl-glucosamine (UDP-GlcNAc) and UDP-MurNAc-pentapeptide. The newly formed polymer was less accessible for lysozyme and more strongly bound to the acceptor than the same product from the Escherichia coli particulate enzyme. After incubation in the presence of penicillin, a greater part of the peptidoglycan was lysozyme sensitive and more loosely bound to the acceptor. The antibiotics enduracidin, moenomycin, prasinomycin, and 11.837 RP inhibited peptidoglycan synthesis by the B. stearothermophilus particulate enzyme. The rate of synthesis of GlcNAc-MurNAc(-pentapeptide)-P-P-phospholipid was independent from the addition of these antibiotics, but its utilization was strongly inhibited. With the present results, it is not possible to distinguish the mechanisms of action of enduracidin, moenomycin, prasinomycin, and 11.837 RP from the mechanisms of action of vancomycin and ristocetin.

A rapid method for the quantitative and qualitative measurement of the initiation of protein synthesis in mammalian cell-free extracts is described. Use of the antibiotic sparsomycin, which inhibits chain elongation but has little effect on initiation, results in the accumulation of short initiation peptides during protein synthesis in vitro. The initiation peptides remain bound to tRNA but are not attacked by the putative aminopeptidase responsible for the removal of N-terminal methionine from nascent polypeptides. After electrophoresis and autoradiography such initiation peptides labelled with [35S] methionine yield a specific fingerprint for each site at which initiation has occurred. The optimal conditions for cell-free incubation, isolation and characterisation of initiation peptides are described.

A new antibiotic O-2867 inhibiting the growth of Piricularia oryzae, a plant pathogenic fungus of rice, was isolated from a Streptomyces sp. Antibiotic O-2867 is water-soluble, amphoteric and consists of 2 components, O- 2867-α and β. O-2867-α was obtained as an amorphous powder and O-2867-β as colorless needles. Both antibiotics are active against P. oryzae in vitro but are not effective in pot tests using rice plants infected with P. oryzae.

The peptidoglycan from two types of filamentous cell division mutants of Agmenellum quadruplicatum strain BG1 has been compared to that of the parent organism. Small variations in the total peptidoglycan composition on a dry-weight basis were found in the mutants. The reduced level of peptidoglycan in the serpentine mutant is consistent with a general decrease in the ratio of surface area to volume as compared to the parent organism. The increased peptidoglycan content in the septate mutant confirms previous ultrastructural observations of the greatly enlarged peptidoglycan septum between adjacent cells. A comparison of peptidoglycan composition and cross-linking in the two types of filamentous mutants of A. quadruplicatum and in drug-induced phenocopies suggests that structural alterations of the peptidoglycan are not involved in the apparent impairments of cellular division. Furthermore, data concerning the relative susceptibilities of the parent and mutants to antibiotics indicate that neither mutant exhibits a gross alteration of permeability.

PRISTINAMYCIN is a new antibiotic obtained from Streptomyces pristinae spiralis, a Streptomyces isolated from a soil sample taken at San Carlos (Cordoba) in Argentina1. It is made up of several components and belongs to the family of synergistic antibiotics which includes streptogramin, staphylomycin and ostreogrycin. Chromatographic analysis has shown that pristinamycin is a mixture of two groups of components, the proportions of which vary within certain fixed limits

During an antibiotic screening programme, a new biologically active complex was isolated from an unidentified Streptomyces, strain Ac6 5691), which was obtained from a garden soil in Calcutta, India. This antibiotic complex was found to contain two water-soluble active fractions of which the major one was designated as boseimycin. This commuication describes the isolation, purification and characterization of boseimycin. It was found to have a close relationship to the streptothricin group of antibiotics but was differentiated from them on the basis of its physico-chemical and microbiological properties.

Novobiocin-supersensitive (NS) mutants which could not grow on plates containing 40 μg or less of novobiocin per ml were isolated from Escherichia coli strain JE1011 (derived from E. coli K-12). Most of these NS mutants were found to have incomplete lipopolysaccharides (LPS), and they lack phosphate diester bridges in their backbone structure, with or without total loss of heptose, to which the phosphate diester is linked, and consequently lack external outer-core oligosaccharides. The phosphate diester bridges in the LPS backbone are apparently very important in forming a cell surface structure resistant to the penetration of antibiotics such as novobiocin, spiramycin, and actinomycin D. NS mutants, with incomplete LPS, lacking phosphates in their backbone structure were found to be resistant to phage T4, and those which also lacked heptose were resistant to phages T4 and T7. In contrast to the generally accepted idea that resistances to phages T3, T4, and T7 are linked genetically, no NS mutant was found to be resistant to T3. The possible structures of the receptors for T4 and T7 are discussed. The positions of novobiocin-supersensitive genes on the chromosome of several of the NS mutants defective in LPS were mapped. The genes were designated lpcA (between ara and lac ) and lpcB (between 55 min and 60 min). The latter seemed to be a group of several related genes.

A rise in Salmonella typhimurium infection was observed in calves in Britain during 1964–6, follwing the adoption of the intensive farming method. A single phage type of S. typhimurium, type 29, was incriminated as the major pathogen. Attempts to treat and control the disease with a range of antibiotics were ineffective, but resulted in the acquisition of transferable multiple drug resistance by type 29. The transmission of drug-resistant type 29, directly or indirectly, from bovines to man resulted in many human infections. Transferable drug resistance reaching man from enterobacteria of animal origin may ultimately enter specifically human pathogens. Infections such as that caused by type 29 can be eliminated, not by the massive use of antibiotics but by improvement in conditions of animal husbandry and reduction in the opportunities for the initiation and spread of the disease. A reappraisal is needed of the methods of using antibiotics to determine how these methods can be improved, in order to conserve the long-term efficacy of the antibiotics.

Five cases of coincident salmonellosis and ulcerative colitis are described. In three the diagnostic combination was recognized late. If corticosteroid therapy is given for the colitis once the combination is recognized, then simultaneous systemic antibiotic cover is advisable. One of the five patients died during corticosteroid therapy alone with salmonella septicaemia due to a usually non-invasive organism.

Over a period of 33 months a total of 2,146 peritoneal dialyses were carried out by means of indwelling Tenckhoff catheters in 65 patients suffering from terminal renal failure. The patients were maintained on peritoneal dialysis for periods varying from two weeks to 13 months. Treatment over long periods was possible in only a few cases. Infection and clotting, which tended to limit the functional life of the catheters, was reduced by rigid asepsis and by adding heparin to the dialysate. The Tenckhoff catheter was found to be valuable for peritoneal dialysis as a short-term measure, especially in patients in whom haemodialysis was not immediately feasible, in borderline cases when kidney function was not too seriously impaired, and as an alternative to haemodialysis when that was interrupted by complications.

Out of 210 isolates of Haemophilus influenzae obtained from the sputum of 63 patients with chronic respiratory infections 109 (52%) were resistant to trimethoprim-sulphamethoxazole by the disc test. The minimal inhibitory concentrations of trimethoprim for 17 out of 18 strains recorded as resistant were 10 mug/ml or higher. Resistant strains were isolated from time to time from 32 (82%) out of 39 patients known to have been treated with trimethoprim-sulphamethoxazole, compared with only 1 (12.5%) out of 8 patients known not to have been treated with this drug combination. Resistant strains were isolated most frequently from patients who had received long-term treatment. Since sulphamethoxazole penetrates from the blood into the bronchial secretions less readily than does trimethoprim it seems likely that the ratio of the two drugs in the bronchial tree is far from ideal. This may be an important factor in the use of these drugs for chest infections.

Fifty patients have been treated with clindamycin, a chemical analogue of lincomycin. Forty-four responded satisfactorily to treatment. Gastrointestinal side-effects were rare though five patients developed rashes. Most recently isolated staphylococci are clindamycin-sensitive.

A new disposable plastic tray for large plate assays of antibiotics was compared with conventional trays with plate-glass bottoms, and was found to be entirely satisfactory.

Large discrepancies in the available data on skin microbiology stimulated investigations of the number, interactions, and location of commensals and the true efficiency of disinfection by using skin biopsy, culture of frozen sections, and other methods.Most current procedures were less than 0.5% as sensitive as the biopsy method described. This gave mean bacterial counts ranging from 4,400/cm(2) on the breast to 400,000/cm(2) in the axillae. An iodine preparation removed 95% of accessible organisms, but about 20% of bacteria were protected by follicles, crevices, and lipids. Commensals in over 20% of people produced antibiotics against a wide range of pathogens. Conversely, "satellitism" was demonstrable in 12% of people.