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Pharmacodynamics and pharmacokinetics of cefdinir, an oral extended spectrum cephalosporin.
BACKGROUND: Oral second and third generation cephalosporins are undergoing continuing research and development in the arena of pediatric infectious disease in an attempt to fill voids created by existing agents in the quest for the "ideal" antimicrobial. This paper reviews the in vitro antimicrobial activity (pharmacodynamics) and pharmacokinetics of cefdinir, an extended spectrum oral cephalosporin, with an emphasis on those aspects relevant to the pediatric patient population. METHODS: A MEDLINE literature search was conducted for the years 1985 through 2000, identifying all English language papers examining the in vitro antimicrobial activity and human pharmacokinetics of cefdinir. Bibliographies of these papers were reviewed, as were relevant data on file with the manufacturer. DATA SYNTHESIS: Cefdinir exhibits broad range in vitro activity against Gram-positive and Gram-negative aerobes. It exhibits superior activity against Gram-positive aerobes, compared with drugs like cefixime, ceftibuten, cefuroxime and cefpodoxime. In addition it is stable to hydrolysis by many of the common betalactamases. The pharmacokinetic parameters of cefdinir in children are similar to those obtained in adults using similar milligram per m2 doses (300, 600 mg in adults = 7, 14 mg/kg in children, respectively). CONCLUSIONS: The pharmacodynamic and pharmacokinetic characteristics of cefdinir as described in this paper, as well as the results of the clinical trials program, support the use of this agent in the treatment of a wide variety of pediatric infectious diseases.
New developments in antibacterial choice for lower respiratory tract infections in elderly patients.
Elderly patients are at increased risk of developing lower respiratory tract infections compared with younger patients. In this population, pneumonia is a serious illness with high rates of hospitalisation and mortality, especially in patients requiring admission to intensive care units (ICUs). A wide range of pathogens may be involved depending on different settings of acquisition and patient's health status. Streptococcus pneumoniae is the most common bacterial isolate in community-acquired pneumonia, followed by Haemophilus influenzae, Moraxella catarrhalis and atypical pathogens such as Chlamydia pneumoniae, Legionella pneumophila and Mycoplasma pneumoniae. However, elderly patients with comorbid illness, who have been recently hospitalised or are residing in a nursing home, may develop severe pneumonia caused by multidrug resistant staphylococci or pneumococci, and enteric Gram-negative bacilli, including Pseudomonas aeruginosa. Moreover, anaerobes may be involved in aspiration pneumonia. Timely and appropriate empiric treatment is required in order to enhance the likelihood of a good clinical outcome, prevent the spread of antibacterial resistance and reduce the economic impact of pneumonia. International guidelines recommend that elderly outpatients and inpatients (not in ICU) should be treated for the most common bacterial pathogens and the possibility of atypical pathogens. The algorithm for therapy is to use either a selected beta-lactam combined with a macrolide (azithromycin or clarithromycin), or to use monotherapy with a new anti-pneumococcal quinolone, such as Levofloxacin ( Levaquin ), gatifloxacin or moxifloxacin. Oral (amoxicillin, amoxicillin/clavulanic acid, cefuroxime axetil (Ceftin)) and intravenous (sulbactam/ampicillin, ceftriaxone, cefotaxime) beta-lactams are agents of choice in outpatients and inpatients, respectively. For patients with severe pneumonia or aspiration pneumonia, the specific algorithm is to use either a macrolide or a quinolone in combination with other agents; the nature and the number of which depends on the presence of risk factors for specific pathogens. Despite these recommendations, clinical resolution of pneumonia in the elderly is often delayed with respect to younger patients, suggesting that optimisation of antibacterial therapy is needed. Recently, some new classes of antibacterials, such as ketolides, oxazolidinones and streptogramins, have been developed for the treatment of multidrug resistant Gram-positive infections. However, the efficacy and safety of these agents in the elderly is yet to be clarified. Treatment guidelines should be modified on the basis of local bacteriology and resistance patterns, while dosage and/or administration route of each antibacterial should be optimised on the basis of new insights on pharmacokinetic/pharmacodynamic parameters and drug interactions. These strategies should be able to reduce the occurrence of risk factors for a poor clinical outcome, hospitalisation and death.
Antibiotic assays in muscle: are conventional tissue levels misleading as indicator of the antibacterial activity?
Concentrations of ampicillin and cefuroxime in serum and muscle were studied in rabbits following a single intramuscular injection of 25 mg/kg. Simultaneous measurements were performed in whole muscle tissue pieces and in muscle tissue fluid obtained by implantation of cotton threads under the muscle fascia. The concentrations in the tissue fluid showed only a short time lag to thea serum levels. However, levels in whole muscle were substantially lower than the corresponding concentrations in muscle tissue fluid, indicating that the antibiotics were not evenly distributed within the tissue. The whole muscle tissue levels seriously underestimated, by a factor of approximately 5 times, the actual antibiotic concentrations in the extracellular fluid, where the microorganisms causing soft tissue infections are most likely to be found.
Cefixime in the treatment of patients with lower respiratory tract infections: results of US clinical trials.
Community-acquired acute lower respiratory tract infections are a common cause of illness, accounting for millions of physician visits and prescriptions each year. Cefixime is an extended-spectrum oral cephalosporin with activity against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis, the most commonly isolated bacterial pathogens. This review presents the results of eight US studies comparing the efficacy and safety of cefixime with those of amoxicillin, amoxicillin/clavulanate, cefaclor, cephalexin, and cefuroxime axetil (Ceftin) in the treatment of patients with acute lower respiratory tract infections. Data for 211 cefixime-treated patients and a range of 19 to 49 patients in the comparator treatment groups were included in the efficacy analysis. Clinical success (cure or improvement) was observed in 94% of cefixime-treated patients; clinical success rates in the comparator treatment groups ranged from 97% for cefuroxime axetil (Ceftin) and cefaclor to 79% for amoxicillin/clavulanate. At the end of treatment, the overall eradication rate in the cefixime treatment group was 92% and ranged from 76% (cefaclor) to 98% (cefuroxime axetil (Ceftin)) in the comparator treatment groups. The percentage of persistent organisms was highest in the cefaclor (24%) and cephalexin (21%) treatment groups. With the exception of the cephalexin group (4%), the incidence of patients who reported adverse experiences was similar across treatment groups (34% to 50%). Those involving the gastrointestinal tract were by far the most common, and most adverse experiences were rated as mild or moderate in severity.
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