Biomedical subjects
Publications and source records attributed to J M Hamilton-Miller.
Many users of antibiotics are unaware of their ionic content. The ionic content is a particularly important factor for injectable beta-lactam compounds in patients on a restricted sodium intake. A table of the sodium content of commonly prescribed beta-lactam compounds is provided.
170 strains of coagulase-negative staphylococci isolated from different patient groups have been characterized: 74% were Staphylococcus epidermidis, 18% S. haemolyticus and 7% S. simulans. There were no differences in rates of isolation of the various species from patients with and without a malignancy. Phage typing was not a useful epidemiological tool, but biotyping was possible using the API Staph system. Slime production, a characteristic said to predispose to colonization of catheters, was found to be most common in S. epidermidis strains.
Stability of aminoglycoside resistance has been investigated in 20 strains of Staphylococcus aureus resistant to gentamicin (16 strains were also resistant to methicillin). In view of previous reports that incubation at elevated temperatures can hasten the loss of unstable antibiotic resistance, we passaged strains daily in a liquid medium for 24 days at 43 degrees C. The nine strains which were resistant to neomycin kept their aminoglycoside resistance virtually intact, whereas most of the other 11 strains (sensitive to neomycin) lost almost all their resistance to gentamicin and kanamycin after 5 days. It thus appears that the stability of aminoglycoside resistances in Staph. aureus is closely linked to the resistance of the strains to neomycin. This finding has important possible consequences in terms of the advisability of the clinical usage of preparations containing neomycin or framycetin for topical application and bowel sterilization.
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Antibiotic-sensitive and multiply-resistant isolates of Staphylococcus aureus and Staph. epidermidis were all sensitive to rifampicin (MIC less than or equal to 0.015) mg/l) and to novobiocin, vancomycin and teicoplanin (MICs less than 1 mg/l). No tolerance was observed. Resistance sometimes developed in bactericidal tests on rifampicin or novobiocin alone, but not with vancomycin or teicoplanin, or with combinations. The implications of these findings are discussed in the context of serious infections with staphylococci, especially those resistant to beta-lactams and aminoglycosides.
The activities of azlocillin and ticarcillin against Pseudomonas aeruginosa were compared by estimating minimum inhibitory and bactericidal concentrations (MIC and MBC) in liquid and solid media, and by constructing killing curves from sequential viable counts. In MIC studies, azlocillin was about three times more active than ticarcillin in solid medium (agar dilution test) and in liquid media (tube and microdilution tests). When the MBC was measured, however, results varied according to the technique used. On agar and in microdilution tests, both azlocillin and ticarcillin were bactericidal, the MBC being 1.3-3 MIC. In the tube test, the MBC for ticarcillin was again about 3 MIC, but azlocillin appeared not to be bactericidal (MBC greater than 1 mg/ml). However, sequential viable counts of four clinical isolates showed that at 4 MIC both antibiotics reduced viable counts by a factor of 10(4) in 8 h. Our results stress the importance of methodology when assessing the antibacterial activity of an antibiotic.
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Forty-four patients (43 female, 1 male), all with a history of recurrent urinary tract infections, were treated with 250 mg of amoxicillin plus 125 mg of clavulanic acid (one tablet of Augmentin) every 8 h for 7 days. The microbiological cure rates were 84% 1 week after the end of treatment and 67% 1 month later. Side effects, which were reported by 20% of the patients, were mild and in no case caused interruption of treatment. In view of the increasing trend in resistance to agents commonly used for the treatment of urinary tract infections in outpatients, the combination of amoxicillin and clavulanic acid may now be considered a first-line drug in patients with recurrent urinary tract infections.
Twelve male subjects, aged 19 to 40 years, shown to be healthy by examination and laboratory tests, took 500 mg of ciprofloxacin every 12 h for 7 days. After the first and the last dose, blood and urine samples were taken and drug concentrations were determined by bioassay. There was a significant buildup in mean concentrations in serum from day 1 to day 7; mean peak levels (attained after 1 to 2 h) were 1.9 and 2.8 micrograms/ml, respectively. The terminal half-life was 3.5 to 4 h. About 40% of the drug was excreted into the urine during the 12-h period after dosing; minimum mean concentrations in urine were 105 micrograms/ml on day 1 and 174 micrograms/ml on day 7. Considerable amounts of ciprofloxacin were found in the feces on day 7 (185 to 2,220 micrograms/g). Marked changes in the aerobic part of the fecal flora were observed as a result of taking ciprofloxacin: coliforms were absent on day 7, and concentrations of streptococci and staphylococci were significantly reduced. There was no overgrowth by yeasts. One week later the fecal flora had returned to a state similar to that found before treatment. Anaerobes were little affected quantitatively but acquired resistance to ciprofloxacin. Side effects were mild and transient.
Significant bacteriuria was found in 19% of 87 women with primary biliary cirrhosis, whereas in 89 women with other types of chronic liver disease bacteriuria was present in only 7%. In 74 women with rheumatoid arthritis 8% were bacteriuric. Midstream urine specimens obtained from 144 consecutive women with primary biliary cirrhosis attending hospital over a two year period showed that 50 (35%) developed bacteriuria during 12 months of follow up. Bacteriuria was unrelated to age, raised serum bilirubin, drug therapy or urinary pH but was more common in patients with late stage (fibrotic) disease as judged by histological criteria. Fifty seven per cent of bacteriuric primary biliary cirrhosis patients suffered more than one urinary infection. Fifty nine per cent of the 156 bacteriuric episodes were asymptomatic. The types of organism isolated, the antibiotic sensitivity patterns and cure rate were similar to those reported in bacteriuric women without other underlying disease. The reinfection rate (34%), however, was double that reported for bacteriuric episodes in 'problem' women with recurrent bacteriuria, indicating a special susceptibility to urinary infection. The most common isolates were E coli (70%), which did not show abnormal adhesiveness to uroepithelial or buccal cells of normal women, or to those of primary biliary cirrhosis patients. Patients with primary biliary cirrhosis have not been reported to be more susceptible to infection in general. Bacteriuria, however, was common throughout all clinical stages of primary biliary cirrhosis. Thus there may be a unique association between bacteriuria and primary biliary cirrhosis.
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A combination of nitrofurantoin (100 mg) and sulphadiazine (300 mg) given 12-hourly for 7 days was used to treat 51 patients with recurrent urinary infections who were attending an out-patient clinic. Either nitrofurantoin or sulphadiazine was active in vitro against all the organisms isolated. The cure rate 1 week after the end of treatment was 82%; 10 patients relapsed during the following month, giving a cure rate 5 weeks after the end of treatment of 57%. Side effects, although relatively common (37%), were mild. The outcome of treatment with these two long-established drugs is thus as good as that obtained with some newer and more expensive preparations.
In an analysis, by both crystallographic and microbiological methods, of 50 urinary calculi recently removed by surgical operation, 33 proved to be of metabolic origin (mostly calcium oxalate and some uric acid or urate) and 17 of 'infective' origin (struvite, apatite or a mixture of the two). Metabolic stones were usually bacteriologically sterile or contained only small numbers (less than 10(3)/g of stone) of bacteria which did not produce urease, while infective stones always contained urease-producing organisms, usually Proteus mirabilis, in large numbers (greater than 10(5)/g). The combined approach of stone analysis by crystallography and microbiological culture yields more information than conventional techniques on which to base the treatment of urinary calculi and the prevention of their recurrence.
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Midstream urines from 237 patients with significant bacteriuria were examined for antibody-coated bacteria (ACB): 113 urines gave a positive result. When more than 25 000 organisms from the ACB-positive urines were scanned either fewer than 100 or more than 250 fluorescent bacteria (ie, greater than 1%) were found: thus the distribution of the fluorescent bacteria was bimodal. To compare the effectiveness of therapy in patients with ACB-positive and ACB-negative bacteriuria, 120 randomly selected patients were given a 7-day course of appropriate therapy. The results were assessed after 6 weeks. In 66 ACB-negative patients the cure rate was 84.8%, which was not significantly different from that found in 26 patients (80.7%) whose urine contained ACB in small numbers (less than 1%). In contrast, in 28 patients whose urine contained greater than 1% ACB the cure rate was only 36%. There was no correlation between the immunoglobulin class coating the bacteria and the response to treatment. The presence of greater than 1% ACB in the midstream urine thus identifies patients who are at high risk of treatment failure.
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