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Urease-negative variants of Helicobacter mustelae were isolated after spontaneous loss of activity during sub-culture. The whole-cell protein patterns showed that the loss of urease activity was linked to the absence of two polypeptides of 29·1 and 65·4 kDa. Restriction endonuclease analysis of chromosomal DNA indicated no substantial differences between the urease negative and positive variants. It is likely that a change in the expression of the gene for urease was responsible for these observations.

Bacteriological sampling of grossly infected or chronic plantar ulcers was performed in 39 untreated patients with leprosy and in 22 patients who had received antibiotic treatment. Samples were cultured aerobically and anaerobically, and films of pus were stained by Gram's method. Stained films gave little indication of the type of infecting pathogen, except when Gram-positive cocci alone were seen. From the ulcers of patients untreated with antibiotics anaerobic streptococci were isolated more frequently than any other organism, and this may be an original observation. Of the 8 Staphylococcus aureus isolates 5 were penicillin sensitive. A range of Gram-negative bacteria, but no Clostridia , were isolated. From the ulcers of patients who had received antibiotics penicillin-resistant Staph. aureus was most frequently isolated. Some Gram-positive bacteria resistant to tetracycline were sensitive to doxycycline.

The surface polysaccharides of Escherichia coli isolated from 6 patients with recurrent urinary infection were studied serologically and chemically. In 4 patients multiple isolates were obtained. The first isolate from each of these patients was a smooth strain which could be serotyped with O antisera. The second isolates from 3 of these patients, obtained at intervals of 1-6 wk, were semi-rough strains. They could not be serotyped after culture on nutrient agar but could be serotyped after subculture on blood agar. In each patient the serotype remained the same. Gel column filtration of the polysaccharides, and gas-liquid chromatography (GLC) of the trimethyl-silylated sugars showed that smooth strains carried a preponderance of O-specific carbohydrate with little core carbohydrate. The semi-rough strains had lost nearly all their O-specific carbohydrate. The change from smooth to semi-rough involved the progressive loss of full length O-specific side-chains rather than a widespread 'shortening' of these side-chains. In patients chronically infected with the same strain of E. coli it has been shown that GLC analysis of the carbohydrates of different isolates of the same strain in one patient will vary because often the strain will undergo a smooth to semi-rough or rough variation. This variation indicates that GLC analysis of extracted carbohydrates would often not be able to determine whether multiple isolates of E. coli from one patient were the same or different strains.

Cefoxitin is the first cephamycin antibiotic having a different structure to cephalosporin antibiotics. Cephamycins are remarkably resistant to all beta-lactamases, but some organisms including Pseudomonas species are resistant to cefoxitin either because the antibiotic fails to penetrate the cell or because the site of antibiotic activity is insensitive to cefoxitin. In Royal Perth Hospital Gram-negative bacteria are tested for their antibiotic sensitivity by inoculation onto agar containing an antibiotic. The concentration of antibiotic in the agar is related to the concentration achievable in clinical situations. Cefoxitin is administered intravenously as 1 g which results in a concentration over 20 mg/l for 60 min, or is administered as 2 g which gives concentrations twice as high. After probenecid and 1 g cefoxitin blood concentrations remain over 25 mg/l for 2 hours. For agar dilution tests the concentration of cefoxitin in the agar was 16 mg/l. Of 481 strains of E. coli tested 99% were sensitive to cefoxitin; all 179 strains of Proteus mirabilis were sensitive, and of 55 indole-positive Proteus strains 94% were sensitive. Of 200 strains of Klebsiella 94% were sensitive; of 35 strains of Citrobacter 56% were sensitive, all 6 strains of Providencia species were sensitive to cefoxitin, and of 21 strains of Serratia 73% were sensitive. Of 39 strains of Acinetobacter 18% were sensitive, and of 83 strains of Enterobacter 16% were sensitive. Cefoxitin, in addition to being active against Gram-positive and Gram-negative organisms, is active against anaerobic organisms. It is thus particularly useful in treating abdominal infections, and in patients with a raised serum creatinine it is likely to be more effective than gentamicin or tobramycin which have to be given at long intervals, and during the slow excretion period relatively inadequate concentrations of the aminoglycoside may not control the infection. At Royal Perth Hospital we have had several patients with abdominal infection and a raised serum creatinine, and cefoxitin has been used very successfully, with ticarcillin. Blood concentrations of 240 mg/l have been obtained without any toxic effects, and thus highly effective concentrations can be maintained without undue risk of toxicity.

The combination of a cephalosporin and a penicillin has previously not been considered to be useful, but cefuroxime and cefamandole have a wider spectrum than older cephalosporins, and ticarcillin is active against Strep. faecalis, Bacteroides and Pseudomonas . If a non-toxic combination such as cefuroxime and ticarcillin could act synergistically to lower bactericidal concentrations these drugs could have a wide clinical application. Six strains of Providencia stuarti were isolated from paraplegics with urinary tract infection. When tested separately the MICs and MBCs of cefuroxime were 64 and 512 mg/l respectively, and of ticarcillin 2 and 512 mg/l. However, the organisms were inhibited by cefuroxime 1 mg/l with ticarcillin 4 mg/1. and killed by cefuroxime 2 mg/1 and ticarcillin 4 mg/l. The patients were treated intramuscularly with ticarcillin 1.5 g b.d. and cefuroxime 750 mg in the morning. and 1 1/2 h after the morning combination the serum was bactericidal to the Providencia at dilutions of 1 in 4 to 1 in 16, and the organisms were eradicated. Cefuroxime and ticarcillin have been found to act synergistically also against some strains of Klebsiella, Enterobacter, Acinetobacter and Strep. faecalis . The MIC of cefuroxime for Strep. faecalis can be mis-read if the inoculum is too small. Repeated studies showed that in 50 isolates of Strep. faecalis the MIC of cefuroxime was 256 mg/l for 12 strains, 512 mg/l for another 31 strains, and 1024 mg/l for the other 5 strains. Although 87 of 100 strains of Strep. faecalis were inhibited by ticarcillin 32 mg/l, the MBC was usually 512 mg/l. At a concentration of cefuroxime of 16 mg/l none of 300 strains of E. coli were resistant to cefuroxime. and of 132 strains of Klebsiella only 3 were resistant, whereas 6 were resistant to cefoxitin. Of 56 strains of Enterobacter 47 were sensitive to cefuroxime but only 6 to cefoxitin. Cefuroxime is also more active than cefoxitin against Acinetobacter , 15 of 27 strains being sensitive, but is less active than cefoxitin against indole-positive Proteus species, Citrobacter and Serratia .