Comparison of a slow-release trimethoprim with co-trimoxazole: efficacy and selection of resistance in the Enterobacteriaceae.

One hundred and fifty one patients with symptoms of urinary tract infection were treated randomly in a double blind study with a slow release form of trimethoprim or with co-trimoxazole. Similar cure rates were seen. There was no difference between the proportions of patients in the two groups who acquired trimethoprim-resistant Enterobacteriaceae. Further clinical trials with slow release trimethoprim should be performed.

Bactericidal effects of norfloxacin towards bacteria in urine.

Norfloxacin produced a reliably bactericidal effect at concentrations from 3 to 90 mg/l against urine pathogens suspended in human urine. These included Enterobacteriaceae, Pseudomonas aeruginosa, Streptococcus faecalis and Staphylococci. Resistant mutants of Staphylococcus aureus were isolated on two occasions (out of 33 experiments). At high concentrations (c. 90 mg/l) the activity was less but this was probably due to the need for a low pH to dissolve the antibiotic. The pH for optimum activity of norfloxacin in urine was 7.5 to 8.0. Human blood had little effect on the bactericidal activity. Compared to other antibiotics, the rate of killing of cultures in urine was second only to gentamicin.

In-vitro evaluation of miokamycin: bactericidal activity against streptococci.

Miokamycin is a diacetyl derivative of the macrolide antibiotic, midecamycin. In vitro, it has an unusual spectrum, inhibiting the growth of Gram-positive cocci and anaerobes, but few Haemophilus spp; enterobacteria are highly resistant. Most erythromycin-resistant Staphylococcus aureus were sensitive (MIC approximately 0.8 mg/l). Resistance to miokamycin in Staph. aureus and streptococci was difficult to select, unless the staphylococci were already resistant to erythromycin. Both miokamycin and erythromycin were bactericidal towards groups A,B,C and G streptococci. Clinical trials of the drug in pelvic, upper respiratory, skin and soft tissue and other staphylococcal infections may be worthwhile.

Double-blind study to compare the selection of antibiotic resistance by amoxycillin or cephradine in the commensal flora.

Elderly patients with acute urinary infections were treated in a double-blind study with either amoxycillin or cephradine. In 52 patients who had received amoxycillin for one week about a third of all intestinal Escherichia coli were highly resistant to amoxycillin, and many were resistant to tetracycline, trimethoprim, or chloramphenicol. Cephradine selected less resistance. At a week after completion of chemotherapy, cephradine-resistant E coli were replaced by sensitive cultures at a greater frequency than were amoxycillin-resistant E coli. Neither antibiotic altered the skin flora. Amoxycillin, but not cephradine, selected for Enterobacteriaceae in the saliva. The propensity of amoxycillin to select resistance in E coli will limit its usefulness in treating urinary infections.

Bactericidal effects of cefotetan and other antibiotics in human fluids.

Antibiotics were added at final concentrations of 0.5 to 10 mg/l to either human blood, serum, urine, bile or ascitic fluid inoculated with sensitive cultures. Bactericidal effects were monitored by estimation of viable counts over 24 h at 37 degrees C. Cefotetan was reliably bactericidal to bacteria suspended in human urine over a wide range of conditions. Gentamicin, cefotaxime, cefotetan and azthreonam were predominantly bactericidal against Enterobacteriaceae in serum and blood; gentamicin, cefotetan and cefotaxime were bactericidal in bile, and cefotetan bactericidal in ascitic fluid. The above antibiotics all also produced a bactericidal effect against Haemophilus influenzae in serum, and the macrolides erythromycin and rosaramicin destroyed haemophilus in serum more rapidly than did ampicillin or amoxycillin. In most of these fluids, destruction (reduction in viable counts by greater than 10-fold) of the inoculum occurred within 2 to 4 h for gentamicin and 4 to 6 h for similar concentrations of beta-lactam agents.

Failure of coagulase-negative staphylococci to transfer antibiotic resistance to Staphylococcus aureus 1030 in mixed cultures.

One hundred and fifty-three isolates of coagulase-negative staphylococci obtained from human skin failed to transfer resistance to either cadmium ions (46 isolates), trimethoprim (37 isolates), erythromycin (25 isolates) or tetracycline (45 isolates) to Staphylococcus aureus strain 1030 or to each of 10 of its lysogenic derivatives in mixed cultures. Thirty-three trimethoprim-resistant coagulase-negative staphylococcal isolates obtained from the human intestine also failed to transfer this resistance to the recipients in mixed cultures.

Comparison of single-dose trimethoprim with a five-day course for the treatment of urinary tract infections in the elderly.

Ninety-six elderly patients (mean age 80 years) with acute urinary infections were treated in a single-blind trial, with either one 200 mg dose of trimethoprim or 200 mg b.d. for five days. After one week the initial pathogen was eliminated in 67% of patients who had received the single dose and in 94% who received the drug for five days. These differences were highly significant (P less than 0.01). After two weeks, the patients who had received trimethoprim for five days were significantly freer from infection than those who had received the single dose. The level of acquired resistance following trimethoprim was small. The single dose of trimethoprim was associated with less suppression of the faecal Enterobacteriaceae and the selection of less resistance in these organisms than the five-day course. Interrupted antibiotic courses may not be particularly prone to select resistance. Trimethoprim was well tolerated in the great majority of patients; only three patients suffered possible side-effects.

Sensitivity of staphylococci to fatty acids: novel inactivation of linolenic acid by serum.

The inhibition of coagulase-negative staphylococci and Staphylococcus aureus of human or animal origin by most free fatty acids was similar, but coagulase-positive staphylococci were sensitive and coagulase-negative cultures were resistant to linolenic acid. Animal strains of S. aureus were more sensitive to linolenic acid than were human strains. These differences were reflected in the relative abilities of the three categories of strains to survive on human skin. The antibacterial effects of 20 mg of linolenic acid were inactivated by 1 ml of serum in vitro. A test organism seeded on to skin also survived better if first suspended in serum. The mechanism of the interaction between serum and linolenic acid may be due to a detergent effect of the serum and could account for colonisation of diseased skin with S. aureus. Cultures of S. aureus seeded on to human skin were rapidly killed after the skin has been covered with linolenic acid. The possibility of therapeutic use of linolenic acid as an antibacterial agent should be explored.

Transfer of gentamicin resistance between cultures of Staphylococcus aureus in nutrient broth, serum and urine.

Only one of 23 gentamicin-resistant cultures of Staphylococcus aureus transferred its resistance in mixed culture in broth to the non-lysogenic S. aureus strain 1030; the transfer-frequency was 10(-3)-10(-4). Transfer between non-lysogenic clones of strain 1030 occurred at a similar frequency in urine, and at a frequency of approximately 10(-1) in serum. The resistance determinant for transfer between non-lysogenic clones was usually linked to phage genome, as shown by the possession by resistant recipients of immunity to typing phage 75, plaque-forming particles in their culture filtrates and inducibility by mitomycin C. Stability of the resistance on storage and transduction kinetics suggested that these genes were chromosomal. Two resistant derivatives were isolated that had lost some phage functions and were unable to transfer their resistance further. The epidemiology of gentamicin resistance may in part be explicable by the transient formation of an auto-transmissible element with subsequent integration of the resistance genes into a variety of replicons (i.e., transposition).

Comparison of trimethoprim alone with trimethoprim sulphamethoxazole in the treatment of respiratory and urinary infections with particular reference to selection of trimethoprim resistance.

279 patients were treated with 100 mg trimethoprim or 100 mg trimethoprim combined with 500 mg sulphamethoxazole (co-trimoxazole) twice daily for 5 days in a prospective randomised double-blind trial. In chest infections in patients in general practice and in an acute geriatric assessment unit, the efficacy of each regimen was similar, but there were more side-effects with co-trimoxazole than with trimethoprim alone. In urinary-tract infections the two regimens also produced similar cure rates. Treatment with trimethoprim rarely selected resistant pathogens in the sputum or resistant Enterobacteriacae in the intestine, although the incidence of resistant coagulase-negative staphylococci on the skin increased with both regimens. Most chest and urinary infections hitherto treated with co-trimoxazole should be treated with trimethoprim alone.