cilastatin--imipenem-drug-combination and Appendicitis

Duration of intravenous (IV) treatment, surgical/radiologic interventions for infection control, and hospital length of stay (LOS) are important cost considerations in complicated intra-abdominal infections (cIAIs).. Data were pooled from two multinational, double-blind studies conducted in hospitalized adults with cIAIs who were randomized (1:1) to receive tigecycline (100 mg IV initial dose then 50 mg IV every 12 h) or imipenem-cilastatin (500 mg IV every 6 h) for 5 to 14 days in order to assess tigecycline safety and efficacy. This report focuses on developing predictors of cure and health care resource utilization, including the need for repeat surgical/radiologic interventions, duration of IV antibiotic therapy, and hospital LOS. Multiple regression models were applied for each of the above outcomes, incorporating both baseline and on-treatment potential covariates. Logistic modeling was used for categorical outcomes (cure; repeat surgical/radiologic interventions) and least squares modeling for continuous outcomes (duration of IV antibiotic therapy; LOS). Stepwise selection was used to retain only those predictors found to be significant (p < 0.05) independent risk factors.. The most common causative pathogen was Escherichia coli (63.0%), with 63.3% of the patients exhibiting polymicrobial infections. The most common cIAI diagnosis was complicated appendicitis (51.9%). Lack of clinical cure (+ 6.1 days; p < 0.0001), perforation of the intestine (+3.7 days; p < 0.0001), an Acute Physiology and Chronic Health Evaluation (APACHE) score >15 (+3.1 days; p=0.039), abnormal plasma sodium concentration (+3.7 days; p=0.026), and repeat surgical/radiologic intervention (+2.2 days; p=0.0097) were identified as key risk factors for longer LOS. Inadequate source control was associated with reduced odds of cure, longer IV treatment duration (+1.5 days; p=0.007), and longer LOS. The treatment groups did not differ in terms of LOS, IV treatment duration, or clinical cure.. Tigecycline was similar to imipenem-cilastatin in terms of both efficacy and health resource utilization. Risk factors identified in this study for both outcome measures are offered as support for guiding clinical practice.

Topics: Abdominal Abscess; Aged; Anti-Bacterial Agents; APACHE; Appendicitis; Cilastatin; Cilastatin, Imipenem Drug Combination; Clinical Trials, Phase III as Topic; Digestive System Surgical Procedures; Double-Blind Method; Drug Combinations; Female; Health Resources; Humans; Imipenem; Length of Stay; Male; Middle Aged; Minocycline; Postoperative Complications; Reoperation; Risk Factors; Tigecycline

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

The efficacy of imipenem-cilastatin was compared with that of tobramycin and metronidazole for the treatment of appendicitis-associated abdominal infections in children in an open, randomized trial. Two hundred eighteen patients between 2.5 and 16.8 years of age hospitalized for appendectomy because of suspected acute appendicitis were allocated to 5 treatment groups. The appendix was perforated in 54 (33.8%) of the 160 cases with appendicitis. All patients responded favorably to treatment. Infection in the wound occurred in 15 of 125 (12.0%) of those without preoperative antibiotic therapy and in 5 of 83 (6.0%) of those given imipenem preoperatively (P = 0.12; 95% confidence interval, -2.2 to 14.2%). C-reactive protein decreased significantly faster in those with perforated appendix treated with imipenem than in those treated with tobramycin and metronidazole (58.2 mg/liter vs. 89.4 mg/liter, P less than 0.05 on the third postoperative day). Imipenem-cilastatin was at least as effective and economically comparable as tobramycin and metronidazole for the treatment of appendicitis-associated infections in children.

Topics: Adolescent; Anti-Bacterial Agents; Appendicitis; Bacterial Infections; Child; Child, Preschool; Cilastatin; Cilastatin, Imipenem Drug Combination; Drug Combinations; Drug Therapy, Combination; Female; Humans; Imipenem; Infant; Male; Metronidazole; Tobramycin

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

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