Controlled clinical trial of pefloxacin versus imipenem in severe acute pancreatitis.

BACKGROUND & AIMS: Antibiotic prophylaxis in severe pancreatitis has recently yielded promising clinical results, with imipenem significantly reducing the incidence of infected necrosis compared with an untreated control group. On the bases of pefloxacin's spectrum of action and pancreatic penetration, we investigated whether such drugs represent a valid alternative to imipenem. METHODS: In a multicenter study, 60 patients with severe acute pancreatitis with necrosis affecting at least 50% of the pancreas were randomly allocated to receive intravenous treatment for 2 weeks with pefloxacin, 400 mg twice daily (30 patients), or imipenem, 500 mg three times daily (30 patients), within 120 hours of onset of symptoms. Age, sex, body weight, Ranson and Apache II scores, C-reactive protein, etiology, and time from onset of symptoms to treatment were well matched in the two groups. RESULTS: The incidences of infected necrosis and extrapancreatic infections were 34% and 44%, respectively, in the pefloxacin group and 10% and 20% in the imipenem group. Imipenem proved significantly more effective in prevention of pancreatic infections (P

Antimicrobial activity of human pancreatic juice and its interaction with antibiotics.

Pancreatic juice (PJ) should be a factor of variability in the antimicrobial activity of antibiotics eliminated by the pancreas during pancreatic infections. We studied its effects on the activity of antimicrobial drugs with different mechanisms of action. Samples of pure PJ were collected from 16 patients with stabilized external pancreatic fistulas. The antimicrobial activity of the juice at different concentrations (from 1.25 to 100%) alone and in combination with mezlocillin, imipenem, ceftriaxone, gentamicin, ofloxacin, and ciprofloxacin was studied by a microbiological method (continuous turbidimetric recording of bacterial growth). The human PJ showed dose-dependent antimicrobial activity that increased directly with the concentration. The activity of the antibiotics at bactericidal concentrations were not modified by the PJ, while the combination with subinhibitory concentrations produced the following variable and different effects: (i) additivity with mezlocillin, ceftriaxone, gentamicin, and ciprofloxacin and autonomy (no interaction) with imipenem and ofloxacin against Providencia rettgeri and (ii) additivity with ceftriaxone, ofloxacin, gentamicin, imipenem, and mezlocillin and autonomy with ciprofloxacin against Escherichia coli. In the presence of PJ, fluoroquinolones showed constant positive effects, while beta-lactams showed more variable antimicrobial activity. Antibiotic concentrations and PJ pharmacodynamics are the main factors determining the final effect of the interaction in vitro. These results may be useful in choosing antibiotics for the treatment of pancreatic infections when they are supplemented with the pharmacokinetic data for each drug.

Antitrypanosomal activity of trivalent antimonials in vitro and its significance.

The SbIII preparations available for clinical use were compared in vitro for their concentration/time/effect curves on Trypanosoma venezuelense (T. evansi), measuring decrease of motility and of parasite numbers. With these two criteria leading to similar relative results, the drugs are classified into a rapidly acting group, led by sodium emetic (AST), followed by its dimethylcysteine chelate (NAP) and Anthiomaline, and a less and more slowly acting one: Triostam, Astiban and Stibophen. The relative activity of these drugs in vitro is parallel to that encountered against Schistosoma mansoni, attributed to a similar pattern of intracellular absorption. In vivo effectiveness may depend on bioavailability of Sb in the host and the direct action on the parasite, reflected by its in vitro activity. The interplay of these two factors leads to a different in vitro/in vivo activity relationship of the antimonials even in the same host (mouse) and to its variation in other host species.