Evaluation of the efficacy and safety of intravenous ciprofloxacin versus meropenem in the treatment of postoperative infection.

Therapeutic options for postoperative infection in gastrointestinal surgery are limited. To identify new treatment alternatives, the Japan Society for Surgical Infection conducted a multicenter prospective, randomized, controlled clinical trial comparing the efficacy of intravenous ciprofloxacin (CIP IV) and intravenous meropenem (MEM IV). Between July 2005 and May 2008, the trial recruited patients who developed postoperative infection or had suspected infectious systemic inflammatory response syndrome after elective clean-contaminated gastrointestinal surgery. All patients had received prophylactic postoperative antibiotic treatment. Patients received either intravenous CIP IV 300 mg b.i.d. or MEM IV 500 mg b.i.d. A total of 205 patients from 31 institutions were enrolled. Of these, 101 were randomized to CIP IV and 104 to MEM IV. There were 100 and 102 in the intent-to-treat (ITT)/safety population and 75 and 77 in the per-protocol (PP) population. There was no significant difference between CIP IV and MEM IV in terms of clinical efficacy, bacteriological efficacy, incidence of adverse drug reactions, duration of antimicrobial treatment, or relapse/reactivation. Overall clinical success PP population) was high in both treatment groups: 85.3% (64/75) for CIP IV and 89.6% (69/77) for MEM IV, although the non-inferiority of CIP IV was not demonstrated (difference -4.3%, 95% CI -14.8, 6.2). In patients who had undergone upper gastrointestinal surgery, success was 88.5% (23/26) for CIP IV and 85.2% (23/27) for MEM IV. Intravenous ciprofloxacin is as effective as intravenous meropenem in the empiric therapy of postoperative infection after gastrointestinal surgery.

Efficacy of bacteriophage therapy against gut-derived sepsis caused by Pseudomonas aeruginosa in mice.

We evaluated the efficacy of bacteriophage (phage) therapy by using a murine model of gut-derived sepsis caused by Pseudomonas aeruginosa that closely resembles the clinical pathophysiology of septicemia in humans. Oral administration of a newly isolated lytic phage strain (KPP10) significantly protected mice against mortality (survival rates, 66.7% for the phage-treated group versus 0% for the saline-treated control group; P<0.01). Mice treated with phage also had lower numbers of viable P. aeruginosa cells in their blood, liver, and spleen. The levels of inflammatory cytokines (tumor necrosis factor alpha TNF-alpha, interleukin-1beta [IL-1beta], and IL-6) in blood and liver were significantly lower in phage-treated mice than in phage-untreated mice. The number of viable P. aeruginosa cells in fecal matter in the gastrointestinal tract was significantly lower in phage-treated mice than in the saline-treated control mice. We also studied the efficacy of phage treatment for intraperitoneal infection caused by P. aeruginosa and found that phage treatment significantly improved the survival of mice, but only under limited experimental conditions. In conclusion, our findings suggest that oral administration of phage may be effective against gut-derived sepsis caused by P. aeruginosa.

Drug susceptibility of isolates from severe postoperative intraperitoneal infections causing multiple organ failure.

PURPOSE: To select the most appropriate antibiotic regimens for life-threatening postoperative infections, we obtained isolates from patients with severe postoperative infections over a 12-year-period, and examined their drug susceptibility. METHODS: The subjects of this study were 55 patients with multiple organ failure (MOF) caused by postoperative infection. RESULTS: All strains of Methicillin-resistant Staphylococcus aureus (MRSA) were susceptible to Vancomycin (VCM) and Teicoplanin (TEIC). Only 0.3% of all the Pseudomonas aeruginosa strains were resistant to Imipenem (IPM), but 53.6% of the strains from the severe infections were resistant to IPM. On the other hand, there were few P. aeruginosa strains resistant to Meropenem (MEPM), Ceftazidime (CAZ), Ciprofloxacin (CPFX), and Pazufloxacin (PZFX), even among strains isolated from severe infections. The resistant rate of Bacteroides fragilis to Clindamycin (CLDM) was 35.9%, but there were strains resistant to IPM and Panipenem. CONCLUSION: These findings suggest that VCM or TEIC are most appropriate for severe abdominal abscess caused by MRSA, whereas MEPM, CAZ, CPFX, and PZFX are more effective against P. aeruginosa infections. The only antibiotic effective against B. fragilis infections in this study was IPM.