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.

In vitro activities of nontraditional antimicrobials against multiresistant Acinetobacter baumannii strains isolated in an intensive care unit outbreak.

Fifteen multiresistant Acinetobacter baumannii isolates from patients in intensive care units and 14 nonoutbreak strains were tested to determine in vitro activities of nontraditional antimicrobials, including cefepime, meropenem, netilmicin, azithromycin, doxycycline, rifampin, sulbactam, and trovafloxacin. The latter five drugs were further tested against four of the strains for bactericidal or bacteriostatic activity by performing kill-curve studies at 0.5, 1, 2, and 4 times their MICs. In addition, novel combinations of drugs with sulbactam were examined for synergistic interactions by using a checkerboard configuration. MICs at which 90% of the isolates tested were inhibited for antimicrobials showing activity against the multiresistant A. baumannii strains were as follows (in parentheses): doxycycline (1 microg/ml), azithromycin (4 microg/ml), netilmicin (1 microg/ml), rifampin (8 microg/ml), polymyxin (0.8 U/ml), meropenem (4 microg/ml), trovafloxacin (4 microg/ml), and sulbactam (8 microg/ml). In the kill-curve studies, azithromycin and rifampin were rapidly bactericidal while sulbactam was more slowly bactericidal. Trovafloxacin and doxycycline were bacteriostatic. None of the antimicrobials tested were bactericidal against all strains tested. The synergy studies demonstrated that the combinations of sulbactam with azithromycin, rifampin, doxycycline, or trovafloxacin were generally additive or indifferent.

A randomized study of cefepime versus the combination of gentamicin and mezlocillin as an adjunct to surgical treatment in patients with acute cholecystitis.

In patients with acute cholecystitis, antibiotics are used as an adjunct to cholecystectomy to reduce the incidence of postoperative septic complications thought to be related to bactibilia. Combinations of penicillins, or cephalosporins or aminoglycosides, or both, are often used. Cefepime is a fourth-generation cephalosporin with excellent activity against gram-positive and gram-negative bacteria, including Pseudomonas species. It has a prolonged serum half-life, allowing twice-daily dosing, and is not nephrotoxic. This study was undertaken to determine whether or not cefepime was as effective as the combination of gentamicin and mezlocillin in patients with acute cholecystitis. One hundred and forty-nine patients were randomized, two to one, to receive cefepime or gentamicin and mezlocillin. Cefepime was given intravenously at 2 grams every 12 hours; gentamicin, 1.0 to 1.5 milligrams per kilograms every eight hours, and mezlocillin, 3 to 4 grams every four to six hours. All patients underwent cholecystectomy. Bile cultures were obtained, and concentrations of cefepime in blood, bile, peritoneal fluid and gallbladder were determined in a subset of patients. There were 56 evaluable cefepime-treated and 34 evaluable gentamicin and mezlocillin-treated patients. Bactibilia was present in 17 of 56 cefepime-treated patients (30.4 percent) and ten of 34 gentamicin and mezlocillin-treated patients (29.4 percent). Enterococci were recovered in six cefepime-treated patients. Clinical and bacteriologic responses were similar for the cefepime-treated and gentamicin and mezlocillin-treated groups, with one failure in each group, a wound infection in a patient receiving cefepime and a subhepatic abscess in a patients receiving gentamicin and mezlocillin. Other measures of outcome, such as the number of days of fever, days nothing by mouth, days of hospitalization and days of antibiotic therapy were similar in both groups. Cefepime, with every 12 hour dosing, achieved extremely high concentrations in all tissues assayed at the time of the operation, a mean of eight hours after administration. Adverse clinical events were similar in both treatment groups. Cefepime is as effective as gentamicin and mezlocillin in preventing septic complications after cholecystectomy for acute cholecystitis. Cefepime requires fewer doses, does not require drug monitoring, is not associated with nephrotoxicity and may therefore prove to be a cost-effective alternative to combination therapy that uses an aminoglycoside.

Endoscopic argon-ion laser phototherapy of bleeding gastric lesions.

An argon-ion laser, coupled to a flexible fiberoptic endoscope, was used to photocoagulate experimentally produced bleeding gastric ulcers in dogs. Argon-ion laser phototherapy rapidly and effectively achieved hemostasis in all bleeding ulcers. Bleeding arteries up to 2 mm in diameter were photocoagulated. Intact normal gastric mucosa was exposed to laser energy for varying periods of time to determine if transmural photothermal injury occurred. Exposure for greater than 15 seconds at 1.0 w of throughput power caused microscopical evidence of transmural injury. Healed, laser-treated ulcers could not be differentiated from nontreated control ulcers or normal stomach one month after injury. The Beer law and the heattransfer factors relating to soft tissues are discussed. The coupled argon-ion laser-endoscope may be a safe tool to treat self-limited superficial bleeding gastric lesions.