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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.

Of 1017 patients admitted to the Royal Perth Hospital Diabetic Survey 142 were found to have significant bacteriuria. In these bacteriuric patients serum pyridoxal concentrations were significantly reduced (P = less than 0.001) when compared with 142 diabetic patients matched for age (+/- 5 years) and sex but without infection of the urinary tract. Measurements were repeated up to 6 mth after antibacterial treatment and serum pyridoxal concentrations were still low. Pyridoxal has a role in immunological competence, and it is possible that the increased incidence of urinary tract infection in patients with diabetes reflects impaired immunological competence due to pyridoxal deficiency.

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 .

In 12 Ethiopian men probenecid given with dapsone caused a significant reduction in urinary excretion of acid-labile dapsone metabolites, and to a lesser extent free dapsone, and also raised the blood-levels of dapsone. The method of estimating serum-levels of dapsone by Schiff-base formation was modified for use with urine.

In twenty-two cases of lepromatous leprosy with acute reaction, flufenamic acid had a significant antipyretic effect, with an accompanying fall in the erythrocyte-sedimentation rate. Erythema nodosum leprosum subsided in 23 out of 25 episodes, and the signs and symptoms of acute leprosy iridocyclitis and neuritis were relieved. High-dosage, short, tapered courses of flufenamic acid, up to 25 mg. per kg., were the most effective, and were well tolerated. One patient given up to 28 mg. per kg. of flufenamic acid had neutropenia but 10 days after therapy, his leucocyte-count had returned to normal.

Patients admitted to the neurosurgical wards of Royal Perth Hospital to undergo elective craniotomy who normally receive antibiotics to prevent post-operative infection were given intravenous cotrimoxazole, and specimens of cerebrospinal fluid were obtained one or two days after the start of treatment. Nine patients received 2 ampoules twice daily; each ampoule contained trimethoprim 80 mg and sulphamethoxazole 400 mg. From 6 of these patients CSF obtained 4-8 h after the dose was found to contain low concentrations of trimethoprim 0.2-0.6 mg/l and sulphamethoxazole 5-33 mg/l. Such concentrations would not be inhibitory for Strep, pneumoniae for which the minimum inhibitory concentration of trimethoprim is 1 mg/l; for coliforms the MIC of trimethoprim is 0.4-1.6 mg/l. Forty-three patients received 4 ampoules twice daily, and CSF specimens obtained 4-7 h after the dose contained trimethoprim 0.7-3.6 mg/l and sulphamethoxazole 10-104 mg/l; in the serum, trimethoprim concentrations were 2.8-12.4 mg/l. Two specimens of CSF were taken 11 h after administration of 4 ampoules and neither drug was found in the specimen. Therefore we conclude that for treating an infection in the CSF 4 ampoules 8-hourly would be required. Thrombophlebitis occurred only in 2 patients. The length of treatment was usually 3 or 4 d, but for patients given the drug for longer periods of 2 or 3 wk the haematological parameters did not show any toxic effects. Four ampoules can be diluted in 250 ml and administered during 1 1/2 h. We conclude that intravenous cotrimoxazole must be given in a dose of 4 ampoules to achieve therapeutic concentrations in the CSF. The wide antibacterial spectrum of cotrimoxazole has resulted in its replacing chloramphenicol on nearly all occasions in the neurosurgical unit. Four ampoules thrice daily have been used to treat successfully Nocardia infection in the vitreous, and systemic infection with Pseudomonaspseudomallei. The latter patient developed a thrombocytopenia after 3 d treatment, and the cotrimoxazole was stopped; but he became febrile again and after 5 d cotrimoxazole 4 ampoules t.d.s. was restarted and his platelet count remained normal.

Septicaemia in patients with a high serum creatinine is difficult to treat effectively with gentamicin or tobramycin because during the slow excretion period relatively inadequate blood and tissue concentrations of the aminoglycoside usually fail to control the septicaemia. In such patients a more effective regimen of treatment is a newer cephalosporin or cephamycin combined with ticarcillin. This combination covers nearly all bacteria because ticarcillin is active against organisms which are not killed by cefuroxime or cefamandole— Pseudomonas aeruginosa. Streptococcus faecalis . and Bacteroides . Ticarcillin is not active against Klebsiella , or Emerobacter but these organisms are nearly all killed by cefuroxime or cefamandole. Of 100 strains of Strep, faecalis 87 were inhibited by ticarcillin 32 mg/l and the remaining strains by 64 mg/l. After intravenous injection of 6 g ticarcillin blood concentrations were 200-400 mg/l, and after 3 g 100-200 mg/l. One patient with faecal peritonitis and a high serum creatinine remained febrile for 3 wk during treatment with gentamicin, ampicillin, and lincomycin. and Klebsiella was isolated from his abdominal drain. After treatment with cefuroxime 1500 mg b.d. and ticarcillin 6 g b.d. he rapidly became afebrile and his drainage fluid became sterile. After 2 wk the dose of cefuroxime was reduced to 750 mg b.d. and ticarcillin to 3 g b.d. Such an antibiotic regimen avoids the use of lincomycin or clindamycin. An old lady with two collections of pus in the abdomen was unsuccessfully treated with oral metronidazole and gentamicin or tobramycin because her high serum creatinine allowed only one dose of the aminoglycoside per day. After cefoxitin and ticarcillin she rapidly improved and went to surgery. In 12 paraplegic patients urinary tract infection due to Pseudomonas in 12 patients and Providencia stuarti in 2 patients was cured with ticarcillin 1 g thrice daily, but relapse occurred in 2 patients with abnormal urinary tracts. In the urine of these patients the peak concentration of ticarcillin was 630-4200 mg/1 and the trough concentration was 150-1500 mg/l. Ticarcillin can produce useful therapeutic concentrations in the cerebrospinal fluid. A patient with meningitis after a skull fracture failed to respond to chloramphenicol and gentamicin but rapidly became afebrile and clinically improved after high doses of ticarcillin and cloxacillin: 7 h after 6 g ticarcillin intravenously the cerebrospinal fluid still contained 25 mg/l.