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96 patients with clinical symptoms of acute pyelonephritis were randomized to 2 weeks treatment with either a fixed combination of pivampicillin and pivmecillinam or to pivampicillin alone. If needed, treatment was first started with the respective parenteral equivalents of the drugs. Acute pyelonephritis was bacteriologically verified in 57 patients, in whom Escherichia coli was isolated in 80% of the cases, Klebsiella in 7% and Proteus mirabilis in 5%. 22 of the 39 patients excluded did not have significant bacteriuria (less than 10(8) c.f.u./l). Combination treatment was superior to pivampicillin/ampicillin alone, in terms of clinical effect, with successful treatment being noted in 93% in the combination group and in 53% in the ampicillin group (p = 0.002). The combination was also more effective bacteriologically and it did not select resistant strains in the urinary tract. Ampicillin treatment alone, was, however, associated with a significant increase in urinary strains resistant to ampicillin and to mecillinam. Unsuccessful responders had a significantly higher mean age (p less than 0.01) than successful responders. No serious side-effects were noted.