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[Cefoperazone concentration in infected tissues and clinical effect for patients with peritonitis (author's transl)]
Insights
Cefoperazone (CPZ), a new cephalosporin antibiotic, effectively treats acute peritonitis and perforated appendicitis. High CPZ concentrations were found in infected tissues and ascites, exceeding minimal inhibitory levels for common pathogens.
Area of Science:
- Pharmacology
- Infectious Diseases
- Surgical Infections
Background:
- Acute peritonitis and perforated appendicitis are severe conditions often requiring antibiotic therapy.
- Beta-lactamase resistance is a critical factor in selecting effective antibiotics for these infections.
- Cefoperazone (CPZ) is a novel cephalosporin antibiotic designed for parenteral administration with enhanced beta-lactamase stability.
Observation:
- This study investigated the pharmacokinetic profile of cefoperazone (CPZ) in patients undergoing surgery for acute peritonitis and perforated appendicitis.
- CPZ was administered intravenously at a dose of 1g during the operation.
- Concentrations of CPZ were measured in purulent ascites and appendix tissue specimens at various intervals post-administration using a paper disk bioassay.
Findings:
- CPZ concentrations in purulent ascites rapidly increased post-injection, peaking within 30 minutes to 1 hour before a slow decline.
- CPZ levels in infected appendix tissue correlated directly with the severity of inflammation, reaching 60.3 mcg/g in severe gangrenous cases.
- Measured CPZ concentrations in ascites and appendix tissue surpassed the minimum inhibitory concentration (MIC) for key pathogens like Escherichia coli and Klebsiella pneumoniae.
Implications:
- Cefoperazone (CPZ) demonstrates promising efficacy for the chemotherapy of acute peritonitis and perforated appendicitis.
- The drug's favorable pharmacokinetic profile and high tissue penetration support its use in managing intra-abdominal infections.
- CPZ's effectiveness against common Gram-negative bacilli implicated in these infections warrants further clinical evaluation.
Abstract:
A new antibiotic drug of cephalosporin, with marked resistance to beta-lactamase, cefoperazone (CPZ) for parenteral use was used in 6 patients with acute peritonitis and perforated appendicitis. CPZ in a dose of 1 g was given intravenously during the operation. Tissue specimens of different sites were taken from removed organs. The materials of purulent ascites and appendix were subsequently taken at intervals. Determination of CPZ concentration was performed according to paper disk bioassay with Micrococcus luteus ATCC 9341 strain. CPZ concentration in purulent ascites increased quickly after injection, and reached high level peak at 30 minutes to 1 hour, then they were very slowly declined. CPZ concentration in the infected appendix, was directly proportional to the degree of pathological changes of inflammation. CPZ concentration in serious gangrenous appendix reached to 50.3 mcg/g at 20 minutes after intravenous injection, and increased to 54.3 mcg/g at 30 minutes, 60.3 mcg/g at 38 minutes, respectively. On the CPZ concentration in patients with appendicitis, the concentration in purulent ascites and appendix were observed higher than the MIC of CPZ for Escherichia coli and Klebsiella pneumoniae bacilli. CPZ therefore will be a very useful drug when used for chemotherapy of acute peritonitis.