minocycline and Appendicitis

Source control, any procedure used to control the source of a major infection, is critical to the resolution of intra-abdominal infections. We sought to characterize whether surgeons agree on methods of source control for patients who had persistent infection despite initial surgical treatment and antimicrobials.. We analyzed source control decisions in a trial comparing tigecycline with imipenem in the treatment of intra-abdominal infections for patients who were clinical failures and had persistent abdominal infections after treatment with antibiotics and undergoing source control.. We found that source control agreement was least among patients who had Acute Physiology and Chronic Health Evaluation (APACHE) II scores greater than 15 (kappa = -.17, P = .533) and those with complicated appendicitis (kappa = .08, P = .446). There was excellent agreement in the source control decisions for perforation (kappa = .76, P = 0.002) and diverticulitis (kappa = 1.00, P = .005).. Agreement on source control is lacking on more severely ill patients and those with complicated appendicitis. These data should be used to seek optimal management for these conditions and to minimize variability in future clinical trials of intra-abdominal infection.

Topics: Abdominal Abscess; Abdominal Cavity; Aged; Anti-Bacterial Agents; Appendicitis; Cholecystitis; Decision Making; Digestive System Diseases; Diverticulitis; Double-Blind Method; Female; Humans; Imipenem; Intestinal Perforation; Male; Middle Aged; Minocycline; Peritonitis; Professional Practice; Tigecycline

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

Topics: Adult; Appendicitis; Bacterial Infections; Child; Clinical Trials as Topic; Female; Humans; Intestinal Perforation; Male; Middle Aged; Minocycline; Penicillins; Peritonitis; Postoperative Care; Streptomycin; Tetracyclines