ABSTRACT
OBJECTIVE: To discuss the pharmacokinetics, spectrum of activity, clinical trials, and adverse effects of cefprozil, cefpodoxime proxetil, loracarbef, cefixime, and ceftibuten, an investigational cephalosporin. DATA SOURCES: Literature was identified by a MEDLINE search from 1986 to January 1995. STUDY SELECTION: Randomized, controlled studies were selected for evaluation; however, uncontrolled studies were included when data were limited for indications approved by the Food and Drug Administration. DATA EXTRACTION: Data were evaluated with respect to in vitro activity, study design, clinical and microbiologic outcomes, and adverse drug reactions. DATA SYNTHESIS: Cefprozil, cefpodoxime proxetil, loracarbef, cefixime, and cefributen are active in vitro against organisms frequently involved in community-acquired infections such as Streptococcus pneumoniae, Escherichia coli, beta-lactamase-positive or -negative Haemophilus influenzae, and Moraxella catarrhalis. Except for cefixime and ceflibuten, they all are active against methicillin-susceptible Staphylococcus aureus. Even though there were problems in study design (discussed within the text), clinical data demonstrate that these new oral beta-lactam compounds are as efficacious as conventional therapies for a variety of community-acquired infections. CONCLUSIONS: Cefprozil, cefpodoxime, cefixime, loracarbef, and ceftibuten demonstrate in vitro activity against the major organisms that cause community-acquired infections. Clinical trials confirm that these agents are as effective as traditional therapies for the management of acute otitis media, pharyngitis/tonsillitis, sinusitis, bronchitis, pneumonia, urinary tract infections, and skin and skin-structure infections. In addition, cefixime and cefpodoxime are effective therapies for uncomplicated gonococcal infections. Selection of a specific agent will be influenced by susceptibility data and safety, as well as issues of compliance and cost.
Subject(s)
Bacterial Infections/drug therapy , Cephalosporins/pharmacokinetics , Cephalosporins/therapeutic use , Prodrugs/pharmacokinetics , Prodrugs/therapeutic use , Cefixime , Cefotaxime/analogs & derivatives , Cefotaxime/pharmacokinetics , Cefotaxime/therapeutic use , Ceftibuten , Ceftizoxime/analogs & derivatives , Ceftizoxime/pharmacokinetics , Ceftizoxime/therapeutic use , Cephalosporins/adverse effects , Humans , Microbial Sensitivity Tests , Prodrugs/adverse effects , Randomized Controlled Trials as Topic , Cefpodoxime Proxetil , CefprozilSubject(s)
Intensive Care Units, Pediatric/organization & administration , Medical Records , Pharmaceutical Preparations/administration & dosage , Adolescent , Child, Preschool , Drug Information Services , Emergencies , Hospital Bed Capacity, 300 to 499 , Hospitals, University , Humans , Illinois , Infant , Infant, Newborn , Patients' RoomsABSTRACT
The chemistry, biological activity, and pharmacokinetics of gamma-interferon and recombinant interferon gamma are reviewed, and the agent's clinical efficacy, adverse effects, and dosage and administration for the treatment of chronic granulomatous disease (CGD) and other disorders are described. Endogenous gamma-interferon is a 166-amino-acid protein encoded by a single gene on chromosome 12. Recombinant human interferon gamma is purified from Escherichia coli as a monomer containing 139 amino acids. Gamma-interferon has antiviral, immunomodulatory, and antiproliferative activity. Serum concentrations of recombinant interferon gamma increase in proportion to the dose. Clearance after i.m. or s.c. administration fits a two-compartment model. The half-life is 3.5-7.5 hours, and bioavailability is 89%. Evidence that recombinant interferon gamma can enhance phagocytic oxidative metabolism led to its evaluation for use in the treatment of CGD. Clinical studies showed that the agent decreases the frequency of serious infections in patients with CGD. Recombinant interferon gamma has shown only limited success in the treatment of metastatic renal cell carcinoma (RCC), both as a single agent and in combination with recombinant interferon alfa. Similarly, although interferons appear to be able to change cytogenetic abnormalities in some patients with Philadelphia chromosome-positive chronic myelogenous leukemia, therapy with recombinant interferon gamma has led to minimal success. However, the agent has produced some encouraging results in atopic dermatitis. The adverse effects of recombinant interferon gamma in patients with CGD usually consist only of fever, chills, headache, and erythema. The recommended dosage in CGD-afflicted children whose body surface area is greater than 0.5 sq m is 50 micrograms/sq m given by s.c. injection three times a week for life. Recombinant interferon gamma has given new hope to patients with CGD. Although the drug is very expensive, the cost may be offset by fewer hospitalizations to treat infection.
