Predictors of efficacy and health resource utilization in treatment of complicated intra-abdominal infections: evidence for pooled clinical studies comparing tigecycline with imipenem-cilastatin.
BACKGROUND
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).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Mallick
Rajiv
R
Wyeth Research, Collegeville, PA 19426-3982, USA. mallicr@wyeth.com
Sun
Steven
S
Schell
Scott R
SR
D018806:APACHE; D018784:Abdominal Abscess / Q000188:drug therapy* / Q000191:economics / Q000209:etiology; D000368:Aged; D000900:Anti-Bacterial Agents / Q000191:economics / Q000627:therapeutic use*; D001064:Appendicitis / Q000150:complications / Q000188:drug therapy / Q000382:microbiology; D015377:Cilastatin / Q000191:economics / Q000627:therapeutic use; D000077728:Cilastatin, Imipenem Drug Combination; D017326:Clinical Trials, Phase III as Topic; D013505:Digestive System Surgical Procedures / Q000009:adverse effects; D004311:Double-Blind Method; D004338:Drug Combinations; D005260:Female; D006295:Health Resources / Q000706:statistics & numerical data; D006801:Humans; D015378:Imipenem / Q000191:economics / Q000627:therapeutic use; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D008911:Minocycline / Q000031:analogs & derivatives* / Q000191:economics / Q000627:therapeutic use; D011183:Postoperative Complications / Q000188:drug therapy* / Q000191:economics / Q000382:microbiology; D012086:Reoperation / Q000009:adverse effects; D012307:Risk Factors; D000078304:Tigecycline
D000900:Anti-Bacterial Agents; D004338:Drug Combinations; D015377:Cilastatin; D000078304:Tigecycline; D015378:Imipenem; D000077728:Cilastatin, Imipenem Drug Combination; D008911:Minocycline