cilastatin--imipenem-drug-combination and Intestinal-Perforation

Complicated intra-abdominal infections (cIAI) remain challenging to treat because of their polymicrobial etiology including multi-drug resistant bacteria. The efficacy and safety of tigecycline, an expanded broad-spectrum glycylcycline antibiotic, was compared with imipenem/cilastatin (IMI/CIS) in patients with cIAI.. A prospective, double-blind, multinational trial was conducted in which patients with cIAI randomly received intravenous (IV) tigecycline (100 mg initial dose, then 50 mg every 12 hours [q12h]) or IV IMI/CIS (500/500 mg q6h or adjusted for renal dysfunction) for 5 to14 days. Clinical response at the test-of-cure (TOC) visit (14-35 days after therapy) for microbiologically evaluable (ME) and microbiological modified intent-to-treat (m-mITT) populations were the co-primary efficacy endpoint populations.. A total of 825 patients received >or= 1 dose of study drug. The primary diagnoses for the ME group were complicated appendicitis (59%), and intestinal (8.8%) and gastric/duodenal perforations (4.6%). For the ME group, clinical cure rates at TOC were 80.6% (199/247) for tigecycline versus 82.4% (210/255) for IMI/CIS (95% CI -8.4, 5.1 for non-inferiority tigecycline versus IMI/CIS). Corresponding clinical cure rates within the m-mITT population were 73.5% (227/309) for tigecycline versus 78.2% (244/312) for IMI/CIS (95% CI -11.0, 2.5). Nausea (31.0% tigecycline, 24.8% IMI/CIS [P = 0.052]), vomiting (25.7% tigecycline, 19.4% IMI/CIS [P = 0.037]), and diarrhea (21.3% tigecycline, 18.9% IMI/CIS [P = 0.435]) were the most frequently reported adverse events.. This study demonstrates that tigecycline is as efficacious as imipenem/cilastatin in the treatment of patients with cIAI.

Topics: Abdomen; Adult; Anti-Bacterial Agents; Appendicitis; Bacterial Infections; Cholecystitis; Cilastatin; Cilastatin, Imipenem Drug Combination; Diverticulitis; Double-Blind Method; Drug Combinations; Female; Humans; Imipenem; Intestinal Perforation; Male; Middle Aged; Minocycline; Peptic Ulcer Perforation; Peritonitis; Tigecycline

The objective of this study was to compare ticarcillin/clavulanate given at 3.1 g every 6 hours with imipenem/cilistatin given at 500 mg every 6 hours for the treatment of infections associated with gangrenous or perforated appendicitis. One hundred thirty-seven patients were found to have gangrenous or perforated appendicitis and received the study medication for 3 to 5 days in a double-blinded, randomized manner. Clinical success was similar for the two treatment groups, 96.9 and 95.9 per cent in the ticarcillin/clavulanate and imipenem/cilistatin groups, respectively (P=0.99; 95% confidence interval for the difference was -5.6% to 7.6%). Bacteriologic success at the end of therapy was similar in the two groups, 100 and 98.4 per cent in the ticarcillin/clavulanate and imipenem/ cilistatin groups, respectively (P=0.99; 95% confidence interval for the difference was -1.8% to 4.7%). The occurrence of adverse events related to treatment was similar for the two groups (P=0.31) and led to study withdrawal for four patients (one with ticarcillin/clavulanate and three with imipenem/ cilistatin). Ticarcillin/clavulanate given at 3.1 g every 6 hours is as effective and as safe as imipenem/ cilistatin given at 500 mg every 6 hours for treatment of gangrenous or perforated appendicitis.

Topics: Adolescent; Adult; Aged; Appendicitis; Appendix; Child; Cilastatin; Cilastatin, Imipenem Drug Combination; Clavulanic Acids; Double-Blind Method; Drug Combinations; Drug Therapy, Combination; Female; Gangrene; Humans; Imipenem; Intestinal Perforation; Male; Middle Aged; Prospective Studies; Ticarcillin; Treatment Outcome

An open-label prospective study was performed employing intramuscularly administered imipenem as an adjunct to surgery in 20 patients with acute cholecystitis and 24 patients with perforated or gangrenous appendicitis. Three (12.5%) septic failures occurred in appendicitis patients and 2 (10%) failures in cholecystitis patients. There were no deaths. Adverse effects were minor, and there was no toxicity. Although failures were not associated with in vitro resistance, Pseudomonas spp. were recovered from 2 of 3 appendicitis failures. Intramuscular imipenem appeared to be an effective single-drug antimicrobial when used as an adjunct to surgery in patients with acute cholecystitis or perforated appendicitis. It should be a more cost-effective alternative to the current multiple-drug therapy frequently employed in patients with intra-abdominal sepsis.

Topics: Adult; Appendicitis; Cholecystitis; Cilastatin; Cilastatin, Imipenem Drug Combination; Combined Modality Therapy; Drug Combinations; Female; Gangrene; Half-Life; Humans; Imipenem; Injections, Intramuscular; Intestinal Perforation; Lidocaine; Male; Prospective Studies; Rupture, Spontaneous

The present study addressed the role of IL-12 in a murine model of septic peritonitis, induced by cecal ligation and puncture (CLP). Although CLP surgery induced IL-12 production at 6 and 24 h after surgery, IL-12 immunoneutralization was clearly deleterious in this model: 54% of CLP mice receiving preimmune serum survived, whereas mice administered IL-12 antisera prior to CLP experienced a 25% survival rate. IL-12 immunoneutralization not only led to increased mortality, but also appeared to promote a shift away from IL-12 and IFN-gamma, in favor of IL-10. This cytokine shift corresponded to changes in bacterial load, as CLP mice receiving IL-12 antiserum yielded more CFUs from the peritoneal cavity at 24 h after CLP. To address the role of bacterial infection in IL-12 antiserum-induced mortality following CLP, antibiotics were administered for 4 days after surgery. Despite regular antibiotic administration, IL-12 immunoneutralization still reduced survival in CLP mice. Furthermore, histology of the ceca revealed that mice administered IL-12 antisera failed to show typical organization of the damaged cecum wall. Accordingly, Gram staining revealed bacteria within peritoneal fluids from these mice, while peritoneal fluids from CLP mice that received preimmune serum and antibiotics were free of bacteria. Altogether, these data suggested multiple important roles for IL-12 in the evolution of murine septic peritonitis.

Topics: Acute Disease; Animals; Cecal Diseases; Cilastatin; Cilastatin, Imipenem Drug Combination; Disease Models, Animal; Drug Combinations; Drug Therapy, Combination; Female; Fibrosis; Imipenem; Immune Sera; Immunization, Passive; Interferon-gamma; Interleukin-10; Interleukin-12; Intestinal Perforation; Ligation; Mice; Peritoneum; Peritonitis; Sepsis; Wound Healing

We report herein the case of a 40-year-old man with AIDS who was admitted to hospital with severe abdominal pain, fever, and chills. He underwent an emergency laparotomy which revealed a perforated appendix with suppurative peritonitis. An appendectomy with peritoneal drainage was carried out, but the postoperative course was complicated by fever without leukocytosis; however, he gradually improved following treatment with intravenous antibiotics, granulocyte colony-stimulating factor (G-CSF) and immunoglobulins, and made a complete recovery. His postoperative course demonstrates the effectiveness of this treatment regimen for patients with AIDS complicated by infection without an increase in the white blood cell count (WBC).

Topics: Acute Disease; Adult; AIDS-Related Opportunistic Infections; Appendectomy; Appendicitis; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Escherichia coli Infections; Fever of Unknown Origin; Granulocyte Colony-Stimulating Factor; Humans; Imipenem; Immunization, Passive; Intestinal Perforation; Male; Postoperative Complications; Rupture, Spontaneous