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In order to measure the incidence of methicillin-resistant Staphylococcus aureus (MRSA) and of Enterobacteriaceae producing extended-spectrum beta-lactamase (ESBLE), and to evaluate the impact of the national guidelines for multidrug-resistant bacteria (MDRB) prevention in hospitals of Northern France, a multicentre study was conducted for three months every year starting in 1996, in volunteer hospital laboratories. All clinical specimens positive for MRSA and ESBLE were prospectively surveyed. During the five-year surveillance period, the overall proportion of MRSA was 38.4% in the 28,534 strains of S. aureus, and that of ESBLE was 11.4% in the 6121 strains of Klebsiella pneumoniae and 47.7% in the 2353 strains of Enterobacter aerogenes. The overall incidence rates of clinical specimens positive for MRSA, ESBL-K. pneumoniae and E. aerogenes were 0.84. 0.05 and 0.12/1000 hospital-days (HD), respectively. In the 23 hospitals that participated in the survey every year, the proportion and incidence of ESBLE decreased. Hence, despite recommendations as for isolation precautions, MRSA remains poorly controlled and requires more effective measures.

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The ciprofloxacin efficacy was compared to that of tobramycin in an Escherichia coli pyelonephritis model in rat. Treatments started 48 h after ligation of the left ureter and inoculation of the bladder and continued for 5 days. Ciprofloxacin (2.5 mg/kg/d and 10 mg/kg/d) was administered intravenously either in a single daily dose or in 2 divided doses at 12 h intervals. Tobramycin (2.5 mg/kg/d and 10 mg/kg/d) was administered by the intramuscular route, in a single daily dose. Ciprofloxacin 10 mg/kg/d was as efficacious as tobramycin irrespective of dosage schedule. Ciprofloxacin 2.5 mg/kg/d was more effective when given twice a day than once.

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The prophylaxis of severe Gram-negative infections with human antiserum to lipopolysaccharide (LPS) was evaluated in a randomised study of 60 patients with therapeutic aplasia for leukaemia. The antiserum was found to be ineffective in preventing Gram-negative infections. The levels of anti-LPS antibodies showed that passive immunization was obtained in only one half of the patients. These disappointing results warrant further investigations to evaluate the effectiveness of this prophylactic treatment.

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The efficacy of ciprofloxacin alone and in combination with azlocillin was compared with that of azlocillin plus tobramycin in a rat model of aortic valve endocarditis due to Pseudomonas aeruginosa. MICs against the infecting strain of ciprofloxacin, azlocillin and tobramycin were 0.125, 8, and 0.5 mg/l, respectively. Antimicrobials were administered 24 h after bacterial challenge and for six days. Mean peak/trough serum levels for ciprofloxacin (50 mg/kg i.v. q 12 h), azlocillin (500 mg/kg i.v. q 12 h) and tobramycin (6.5 mg/kg i.v. q 12 h) were: 10.5/0.2, 386/less than 16, and 6.2/less than 0.6 mg/l, respectively. Ciprofloxacin alone was more effective than the combination azlocillin-tobramycin in increasing survival (p less than 0.05), sterilizing blood (p less than 0.05) and valves (p less than 0.001), and in reducing bacterial titers in vegetations (p less than 0.001). Ciprofloxacin-azlocillin combination was not more effective than ciprofloxacin alone. Drug resistance was not encountered in post-treatment isolates with any therapy regimen.

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Unilateral pyelonephritis was induced in 50 rabbits by injecting Escherichia coli (minimum inhibitory concentration of tobramycin 0.25 mg/l) into the left kidney and by obstructing the ureter temporarily. Tobramycin treatment (daily dose 10 mg/kg) was started 4 days after surgery, either in a single daily dose or in 3 divided doses at 8 h intervals, for 2, 3, 5, 7 or 10 days. Comparison of bacteriology, renal morphology, and renal functions (BUN, serum creatinine, alanine aminopeptidase, N-acetyl-beta-D-glucosaminidase, cathepsin B, sphingomyelinase) suggests better efficacy and renal tolerance of the single daily dose regimen in the treatment of experimental acute pyelonephritis.

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Unilateral acute pyelonephritis were produced in rabbits by injecting E. coli, using the retrograde route and after a temporary ureteral obstruction. Animals were treated with ceftriaxone IM at a dose of 50 mg/kg/d and 100 mg/kg/d (corresponding to 1 g/d and 2 g/d in humans) either by a single daily injection or by two daily injections at 12th intervals. Sacrifices were performed at day 5 and 7 of therapy. Analysis of bacteriological, morphological and histological data obtained in infected kidneys demonstrates that the single daily injection of ceftriaxone is more effective than the same dose divided in two injections at 12 h intervals. These results are observed as well with low and high doses of ceftriaxone.

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From April to July 1984, all of the strains recovered by 10 private laboratories in Upper-Normandy region (France) from urine samples from outpatients seen in office practices (public and private hospitals excluded) were preserved. A total of 829 strains were collected, identified and tested against antibiotics using disk diffusion techniques. These investigations, together with a synthesis of clinical findings, were carried out by the Laboratory of Bacteriology of the Rouen University Hospital. 78.1% of patients were females; all age groups were represented with a greater prevalence of subjects aged 26 to 35 and above 66. E. coli was the most prevalent pathogen (74.5% of all strains), followed by Proteus and Providencia (10%). E. coli was recovered in 78% of first infections against 67.7% of recurrent infections and 50% of prostatitis. More than 25% of strains were resistant to ampicillin; norfloxacin showed the best activity, with 96.5% of susceptible strains.

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The main complication of chronic ambulatory peritoneal dialysis is peritoneal infection due to contamination while handling dialysate bags. For this reason antibiotics should be added to the dialysate to prevent infection. Some antibiotics are known to be unstable when dissolved in dialysate. We therefore studied the bactericidal activity of eight second or third generation cephalosporins against Escherichia coli and Staphylococcus aureus under conditions similar to in vivo situations. Comparison of killing curves shows that bactericidal activity is unchanged after 24 hours in the dialysis fluid at room temperature.

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