Non-hospital antimicrobial usage and resistance in community-acquired Escherichia coli urinary tract infection.

OBJECTIVES: To investigate the correlation between non-hospital antimicrobial consumption and resistance. METHODS: Information on the non-hospital sales of antimicrobials from 14 European countries in 1997 and 2000 was compared with the antimicrobial resistance profiles of Escherichia coli isolated from women with community-acquired urinary tract infection in the same countries in 1999/2000. RESULTS: There was no statistically significant correlation between the consumption of and resistance to co-amoxiclav, cefadroxil, fosfomycin, mecillinam, sulfamethoxazole, trimethoprim or trimethoprim-sulfamethoxazole. On the other hand, there were statistically significant correlations between consumption of broad-spectrum penicillins and quinolones in 1997 and 2000 and resistance to ciprofloxacin (P range 0.0005-0.0045) and nalidixic acid (P range 0.0013-0.0049). Total antimicrobial consumption in 1997 was significantly correlated to ciprofloxacin (P=0.0009) and nalidixic acid (P=0.0018) resistance, and there were significant relationships between quinolone consumption in both years and resistance to gentamicin (P range 0.0029-0.0043) and nitrofurantoin (P range 0.0003-0.0007). E. coli with multiple antimicrobial resistance were significantly more common in countries with high total antimicrobial consumption. CONCLUSIONS: Owing to the frequent presence of many possible confounding factors, antimicrobial resistance to one drug does not always correlate well to the consumption of the same drug or closely related drugs. This study showed that the degree of antimicrobial consumption was significantly correlated to the incidence of multidrug-resistant E. coli.

Three days of pivmecillinam or norfloxacin for treatment of acute uncomplicated urinary infection in women.

Pivmecillinam is a unique beta-lactam antimicrobial that has been used for the treatment of acute uncomplicated urinary infection for > 20 y. Since this agent was introduced, the quinolone antimicrobials have become widely used for the same indication. This study compared the efficacy of a 3-d regimen of pivmecillinam 400 mg b.i.d. with norfloxacin 400 mg b.i.d. Women aged between 18 and 65 y presenting with symptoms of acute cystitis of < 7 d duration were eligible for enrollment; 483 were randomized to receive pivmecillinam and 471 to receive norfloxacin. In each group, 30% of women had negative urine cultures prior to therapy. Bacteriologic cure at early post-therapy follow-up was achieved in 222/298 (75%) pivmecillinam patients and 276/302 (91%) norfloxacin patients [p < 0.001; 95% confidence interval (CI) 12.0-21.8]. Clinical cure/improvement at Day 4 following initiation of therapy was observed in 434/457 (95%) women who received pivmecillinam and 425/442 (96%) who received norfloxacin (p = 0.39; 95% CI 1.5-3.9). Early post-therapy (11 +/- 2 d) clinical cure was achieved in 360/437 women (82%) who received pivmecillinam and 381/433 (88%) who received norfloxacin (p = 0.019; 95% CI 0.9-10.3). In women aged < or = 50 y, early clinical cure rates were 294/351 (84%) for pivmecillinam and 299/340 (88%) for norfloxacin (p = 0.11; 95% CI 1.0-9.4). Adverse effects were similar for both regimens, and there was no evidence of the emergence of organisms of increasing resistance with therapy. Short-course therapy with norfloxacin was superior to that with pivmecillinam in terms of bacteriologic outcome, although differences in clinical outcome were less marked. In conclusion, short-course therapy with pivmecillinam is an effective empirical treatment for pre-menopausal women.

A phase I study of the vitamin D analogue EB 1089 in patients with advanced breast and colorectal cancer.

Preclinical studies have shown that the vitamin D analogue EB 1089 has significantly less calcaemic activity than its parent compound 1,25-dihydroxyvitamin D (1,25(OH)2D3) and significant anti-tumour activity. This phase I trial was designed to evaluate the calcaemic effect of the drug in patients with advanced cancer. EB 1089 was given to 36 patients with advanced breast and colorectal cancer in doses of between 0.15 and 17.0 microg m(-2) day(-1). Serial serum and urine calcium, urine creatinine and serum parathyroid hormone (PTH) were monitored. Hypercalcaemia was seen in all patients receiving 17.0 microg m(-2) day(-1). Hypercalcaemia attributable to EB 1089 was reversible by discontinuing or reducing EB 1089 therapy. During the first 5 days of treatment, urine calcium (P = 0.0001) and serum-corrected calcium (P = 0.027) were related to EB 1089 dose, whereas serum parathyroid hormone (P = 0.0001) showed an inverse relationship. Twenty-one patients received compassionate treatment for between 10 and 234 days. No complete or partial responses were seen. Six patients on treatment for more than 90 days showed stabilization of disease. EB 1089 was well tolerated and adverse events considered to be caused by EB 1089 were limited to dose-dependent effects on calcium metabolism. The dose estimated to be tolerable for most patients from this study is around 7 microg m(-2) day(1). These data support previous work that has demonstrated EB 1089 to be significantly less calcaemic than 1,25-dihydroxyvitamin D3.

Placebo controlled trial of fusidic acid gel and oxytetracycline for recurrent blepharitis and rosacea.

A prospective, randomised, double blind, partial crossover, placebo controlled trial has been conducted to compare the performance of topical fusidic acid gel (Fucithalmic) and oral oxytetracycline as treatment for symptomatic chronic blepharitis. Treatment success was judged both by a reduction in symptoms and clinical examination before and after therapy. Seventy five per cent of patients with blepharitis and associated rosacea were symptomatically improved by fusidic acid gel and 50% by oxytetracycline, but fewer (35%) appeared to benefit from the combination. Patients with chronic blepharitis of other aetiologies did not respond to fusidic acid gel but 25% did benefit from oxytetracycline and 30% from the combination. Our results demonstrate the need to investigate patients with blepharitis for concomitant rosacea as they respond well to targeted therapy.

The combination of pivmecillinam and pivampicillin in the treatment of enteric fever.

Thirty-nine patients with acute enteric fever received the fixed-dose oral combination of pivmecillinam/pivampicillin. Thirty-seven (95%) subjects responded satisfactorily. No relapses or persistent faecal excretion of salmonellae were seen in the 29 patients followed up for 2 to 19 weeks. The treatment was well tolerated, no side-effects being recorded. In vitro studies revealed a synergistic interaction between mecillinam and ampicillin against isolates of Salmonella paratyphi A.

Pivmecillinam for bacteriuria in pregnancy.

Pivmecillinam was given to 44 women with bacteriuria in pregnancy. Treatment was successful in 33 (87%) out of the 38 patients assessed. Thirty women subsequently received at random either a low-dose of pivmecillinam for up to three months or acted as a control group. Further bacteriuric episodes during pregnancy were recorded only in three patients in the control group. Thirty-nine out of the 41 women followed to term delivered healthy babies. One infant was stillborn and another child had a cleft palate. Neither was considered to be related to treatment with pivmecillinam.

Pivmecillinam, co-trimoxazole and oral mecillinam in gastroenteritis due to Vibrio spp.

The comparative efficacy of antibacterial therapy with pivmecillinam or cotrimoxazole and general supportive care only was studied in patients with severe bacterial gastroenteritis. Overall, treatment with antibiotics proved significantly superior to rehydration alone in 42 children. Active therapy also had a statistically beneficial effect in children infected with Vibrio cholerae and V. parahaemolyticus. Pivmecillinam and co-trimoxazole were equally effective. Pivmecillinam and oral mecillinam appeared to be of equal value in a further 22 adults infected by Vibrio spp. No side-effects were recorded in any of the subjects treated. Further investigations with pivmecillinam and oral mecillinam are advocated.