Comparison of intravenous/oral ciprofloxacin plus metronidazole versus piperacillin/tazobactam in the treatment of complicated intraabdominal infections.

OBJECTIVE: To compare the safety and efficacy of intravenous (IV) ciprofloxacin plus IV metronidazole (CIP+MET) with that of IV piperacillin/tazobactam (PIP/TAZO) in adults with complicated intraabdominal infections, and to compare the efficacy of sequential IV-to-oral CIP+MET therapy with that of the IV CIP-only regimen. SUMMARY BACKGROUND DATA: Treatment of intraabdominal infections remains a challenge, mainly because of their polymicrobial etiology and attendant death and complications. Antimicrobial regimens using sequential IV-to-oral therapy may reduce the length of hospital stay. METHODS: In this multicenter, randomized, double-blind trial involving 459 patients, clinically improved IV-treated patients were switched to oral therapy after 48 hours. Overall clinical response was the primary efficacy measurement. RESULTS: A total of 282 patients (151 CIP+MET, 131 PIP/TAZO) were valid for efficacy. Of these patients, 64% CIP+MET and 57% PIP/TAZO patients were considered candidates for oral therapy. Patients had a mean APACHE II score of 9.6. The most common diagnoses were appendicitis (33%), other intraabdominal infection (29%), and abscess (25%). Overall clinical resolution rates were statistically superior for CIP+MET (74%) compared with PIP/TAZO (63%). Corresponding rates in the subgroup suitable for oral therapy were 85% for CIP+MET and 70% for PIP/TAZO. Postsurgical wound infection rates were significantly lower in CIP+MET (11%) versus PIP/TAZO patients (19%). Mean length of stay was 14 days for CIP+MET and 17 days for PIP/TAZO patients. CONCLUSION: CIP+MET, initially administered IV and followed by CIP+MET oral therapy, was clinically more effective than IV PIP/TAZO for the treatment of patients with complicated intraabdominal infections.

Endothelial cell apoptosis is accelerated by inorganic iron and heat via an oxygen radical dependent mechanism.

BACKGROUND: Iron participates in diverse pathologic processes by way of the Fenton reaction, which catalyzes the formation of reactive oxygen species (ROS). To test the hypothesis that this reaction accelerates apoptosis, we used human umbilical vein endothelial cells (HUVECs) as surrogates for the microvasculature in vivo. METHODS: HUVECs were loaded with Fe [III](ferric chloride and ferric ammonium citrate) with 8-hydroxyquinoline as carrier and were then challenged with two stimuli of the heat shock response, authentic heat or sodium arsenite. Iron dependence was tested with two chelators, membrane-impermeable deferoxamine and membrane-permeable o-phenanthroline. The role of ROS was assessed with superoxide dismutase, catalase, and the reporter compound dichlorofluorescein diacetate. The mechanism of cell death was assessed with three complementary techniques, Annexin V/propidium iodide labeling, the TUNEL stain, and electron microscopy. RESULTS: Iron-loaded HUVECs executed apoptosis after a heat shock stimulus. Iron-catalyzed formation of ROS appeared to be a critical mechanism, because both chelation of iron and enzymatic detoxification of ROS attenuated this apoptosis. CONCLUSIONS: Inorganic iron, in concert with chemical and physical inducers of the heat shock response, may trigger apoptosis. The accumulation of iron in injured tissue may thereby predispose to accelerated apoptosis and account, in part, for poor wound healing and organ failure.

Limited role of barium enema examination preceding colostomy closure in trauma patients.

Whether trauma patients should undergo barium enema (BE) examination of the colon prior to colostomy closure has recently been questioned. To ascertain the utility of BE and its impact on postoperative course in this patient population, we reviewed 86 trauma patients who underwent colostomy closure during a 12-year period at our institution. There were 82 males and four females with an average age of 28 years. Ninety-five percent of the injuries were the result of penetrating trauma. Sixteen patients had rectal injuries. Fifteen of these had BE greater than 6 weeks post-trauma and all showed healing of the injury. Of the 70 patients with colonic injuries, 43 (group 1) had BE prior to colostomy closure. Ninety-eight percent (n = 42) of these studies were negative. The only positive finding did not affect the planned surgical procedure. Group 2 (n = 27) did not have a BE prior to colostomy closure. Overall complication rates were not significantly different between group 1 (18.6%) and group 2 (29.6%). We conclude that BE prior to colostomy closure for colonic injuries yields little useful information and does not affect the morbidity rate prior to colostomy closure. Its routine usage should be abandoned. The role of barium enema in assessing rectal injury status is less clear because of the small number in our series, but probably offers no advantage over proctoscopy.

Antioxidants modulate induction of programmed endothelial cell death (apoptosis) by endotoxin.

OBJECTIVE: To evaluate the potential role of reactive oxygen metabolites as signals for endothelial cell apoptosis. DESIGN: A series of antioxidants were evaluated for their ability to block apoptosis in cultured porcine aortic endothelial cells in vitro. RESULTS: Scavenging of the hydroxyl radical with the membrane-permeable scavenger dimethyl sulfoxide or blocking its generation via the Fenton reaction by the chelation of iron with o-phenanthroline blocked apoptosis, whereas the cell membrane-impermeable scavengers superoxide dismutase and catalase did not block apoptosis. Inhibition of xanthine oxidase with enzyme-inhibitory levels of allopurinol also failed to block apoptosis, whereas high levels of allopurinol, which also scavenge the hydroxyl radical in vitro, conferred protection. In each case (dimethyl sulfoxide, o-phenanthroline, and high-dose allopurinol), hydroxyl radical ablation was only effective when administered before the priming step (lipopolysaccharide) and was ineffective when administered later, prior to the activation step (heat shock). CONCLUSIONS: These findings suggest a novel role for the hydroxyl radical as a nonlethal intracellular signal in endothelial cell apoptosis. Moreover, the results support a role for programmed cell death in the pathogenesis of multiple organ dysfunction syndrome and suggest novel strategies for prophylaxis and therapy of the most common cause of death in surgical intensive care units.