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• W1825697777 abstract "Overall, respiratory tract infections are one of the major causes for patients to seek medical assistance: in a national health survey conducted in the USA in the 1980s, they were estimated to account for over 200 million infection episodes per annum [1Dixon RE Economic costs of respiratory tract infections in the United States.Am J Med. 1985; 78: 45-51Abstract Full Text PDF PubMed Scopus (105) Google Scholar]. The etiologies of upper and lower respiratory tract infections have been extensively investigated. Viruses are involved in the majority of cases of tonsillopharyngitis, but the most relevant agent of this common disease is group A β-hemolytic streptococcus, which is responsible for approximately 80% of all bacterial pharyngitis cases. In approximately two-thirds of cases of acute otitis media, a bacterial pathogen can be isolated from the middle ear fluid, and respiratory viruses—alone or combined with bacterial pathogens—have been identified in approximately one-fifth of middle ear effusions. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis are most frequently involved [2Klein JO Otitis media.Clin Infect Dis. 1994; 19: 823-833Crossref PubMed Scopus (298) Google Scholar]. The same species also represent the most important causes of acute sinusitis. In lower respiratory infections, although the exact place of bacterial pathogens in acute and chronic bronchitis is uncertain, H. influenzae, S. pneumoniae and M. catarrhalis are commonly cultured from sputum of patients, and may be critical at least in producing the characteristic exacerbations of chronic bronchitis. Finally, S. pneumoniae and H. influenzae are considered the most important bacterial causes of community-acquired pneumonia. Amoxicillin is still considered the drug of choice for the treatment of both acute otitis media and acute sinusitis, due to its 20-year record of clinical success, limited side-effects and low cost. Oral penicillin V, given three or four times daily for 10 days, or intramuscular benzathine penicillin, are the standard treatment for streptococcal tonsillopharyngitis. However, amoxicillin is ineffective against β-lactamase-producing strains of H. influenzae and M. catarrhalis and against penicillin-resistant pneumococci. The percentage of nontypeable H. influenzae organisms that cause otitis media and produce β-lactamases is currently over 30% (approaching 40% in some countries), and the Alexander Project study has shown that the proportion of β-lactamase-producing strains of M. catarrhalis has significantly increased in Europe, i.e. from 70% in 1992 to 82% in 1993 [3Berk SL Kalbfleisch JH The Alexander Project Collaborative Group Antibiotic susceptibility patterns of community-acquired respiratory isolates of Moraxella catarrhalis in Western Europe and in the USA.J Antimicrob Chemother. 1996; 38: 85-96Crossref PubMed Google Scholar], while in USA nearly all strains are β-lactamase producers. For S. pneumoniae, the cumulative resistance to penicillin was estimated in 1993 at 23%, the highest prevalence being reported in Spain and in France and the lowest in other European countries including Italy, where only intermediate resistance was described [4Goldstein FW Acar JF The Alexander Project Collaborative Group Antimicrobial resistance among lower respiratory tract isolates of Streptococcus pneumoniae: results of a 1992–93 Western Europe and USA collaborative surveillance study.J Antimicrob Chemother. 1996; 38: 71-84Crossref PubMed Google Scholar]. As a consequence of this worldwide spread of resistance, there is now major concern about the optimal antibiotic treatment for acute sinusitis and acute otitis media. Assuming that H. influenzae, S. pneumoniae and M. catarrhalis can be responsible for approximately 25%, 30% and 10%, respectively, of acute otitis media cases, and that 30% of H. influenzae, 10% of S. pneumoniae and 80% of M. catarrhalis strains are penicillin-resistant, the use of amoxicillin in the treatment of acute otitis media can be calculated to produce a risk of microbiological and clinical failures in approximately 19% of patients, i.e. 8% for H. influenzae, 3% for S. pneumoniae and 8% for M. catarrhalis. Although group A β-hemolytic streptococcus has not developed penicillin resistance, bacteriological failure rates following the administration of either benzathine penicillin intramuscularly or penicillin V orally for the treatment of streptococcal pharyngitis, have increased from 5%–10% to 20%–30% over the past 30 years. Several hypotheses have been advanced to account for the increasing failure of penicillin in this setting, including lack of compliance, increased number of β-lactamase-producing oropharyngeal flora, penicillin tolerance, and suppression of host immunity with early antibiotic use. With regard to compliance to antibiotic treatment, it should be noted that oral penicillin is generally administered three to four times a day, and the recommendation is usually made that the antibiotic be taken on an empty stomach 1 h before or 2 h after meals. Antibiotic regimens that require multiple daily doses, particularly with the avoidance of meals, may indeed lead to diminished compliance, particularly as soon as patients' symptoms begin to improve. Furthermore, an early study of compliance related to drug administration frequency demonstrated that if a drug is prescribed four times daily, 70% of patients fail to take 25%–50% of the prescription; for three times a day doses, 60% fail; for twice a day dosing, 30% fail; and for once daily dosing, 7% fail [5Ayd Jr., FJ Single daily dose of antidepressants.JAMA. 1974; 230: 263-264Crossref PubMed Scopus (62) Google Scholar]. Taken together, these observations suggest that enhanced bacteriological eradication should be achieved when antibiotics are used that are resistant to β-lactamase degradation and/or bactericidal against these ‘copathogens’, and that can be administered in once-daily dose, for the treatment of streptococcal pharyngitis. The development of the oral third-generation cephalosporins represents a major advance in antibiotic therapy. These compounds, characterized by considerably greater activity against Gram-negative bacilli and increased resistance to β-lactamases, constitute an effective, well-tolerated, broad-spectrum treatment of several types of infection in outpatients. They may also be used as an early replacement, or even an alternative to, parenteral antibiotics. In comparison with the older oral cephalosporins the more recent oral cephalosporins are characterized by intrinsically greater antimicrobial activity and, especially cefixime, by longer serum elimination hall-lives. They can therefore be administered in twice-daily dosing regimens and, in the case of cefixime, also once-daily. Cefixime displays excellent activity in vitro against both β-lactamase-producing H. influenzae and M. catarrhalis and a good activity against both penicillin-sensitive S. pneumoniae and S. pyogenes. Comparatively, cefixime exhibits a better activity against β-lactamase-producing H. influenzae and M. catarrhalis than do ampicillin, erythromycin, sulfisoxazole or cefaclor. The activity of cefixime against S. pneumoniae and S. pyogenes is somewhat lower than that of ampicillin, but is still high [6Bluestone CD Review of cefixime in the treatment of otitis media in infants and children.Pediatr Infect Dis. 1993; 12: 75-82Crossref Scopus (19) Google Scholar]. Furthermore it has recently been shown that the mean cefixime concentration in middle ear fluid during otitis media with effusion exceeds the MIC90 for common middle ear pathogens except for penicillin-resistant pneumococci [7Harrison CJ Chartrand SA Rodriguez W et al.Middle ear effusion concentrations of cefixime during acute otitis media with effusion and otitis media with effusion.Pediatr Infect Dis J. 1997; 8: 816-817Crossref Scopus (8) Google Scholar]. Owing to these favorable microbiological and pharmacodynamic characteristics, cefixime treatment of upper and lower respiratory tract infections and otitis media has been studied in several noncomparative and comparative studies. In streptococcal pharyngitis, its global clinical efficacy in several large studies of both children and adult patients was found to be 98% [8Hausen TH Weidlich G Schmitt J Safety and efficacy of cefixime in the treatment of respiratory tract infections in Germany.Infection. 1995; 23: S65-S69Crossref PubMed Scopus (6) Google Scholar]; in four comparative studies vs. penicillin V its clinical efficacy was comparable with that of penicillin [9Peyramond D Tigaud S Brernard Query C et al.Multicenter comparative trial of cefixime and phenoxymethylpenicillin for group A beta-hemolytic streptococcal tonsillitis.Curr Ther Res. 1994; 55: 14-21Abstract Full Text PDF Scopus (25) Google Scholar, 10Dorow P Safety and efficacy of cefixime versus cefaclor in respiratory tract infections.J Chemother. 1989; 1: 257-260PubMed Google Scholar, 11Block SL Hedrick JA Tyler RD Comparative study of the effectiveness of cefixime and penicillin V for the treatment of streptococcal pharyngitis in children and adolescents.Pediatr Infect Dis J. 1992; 11: 919-925Crossref PubMed Scopus (51) Google Scholar, 12Kiani R Johnson D Nelson B Comparative, multicenter studies of cefixime and amoxicillin in the treatment of respiratory tractinfections.Am J Med. 1988; 85: 6-13Abstract Full Text PDF PubMed Scopus (36) Google Scholar, 13Adam D Hostalek U Troster K 5 day cefixime therapy for bacterial pharyngitis and/or tonsillitis: comparison with 10 day penicillin V therapy.Infection. 1995; 23: 83-86Crossref PubMed Scopus (48) Google Scholar]. In fact, percentages of eradication of β-hemolytic streptococcus were sometimes observed to be significantly higher than those of penicillin, both at the end of treatment and during follow-up. It should also be noted that in one trial [9Peyramond D Tigaud S Brernard Query C et al.Multicenter comparative trial of cefixime and phenoxymethylpenicillin for group A beta-hemolytic streptococcal tonsillitis.Curr Ther Res. 1994; 55: 14-21Abstract Full Text PDF Scopus (25) Google Scholar] compliance was significantly better in the cefixime group and that symptoms (i.e. sore throat and fever) disappeared significantly faster with cefixime. Hausen et al. [8Hausen TH Weidlich G Schmitt J Safety and efficacy of cefixime in the treatment of respiratory tract infections in Germany.Infection. 1995; 23: S65-S69Crossref PubMed Scopus (6) Google Scholar] reported that, among 1854 children and adults suffering from acute or chronic sinusitis, between 98.3% and 100% were cured or improved following treatment with cefixime. The efficacy and safety of cefixime have also been extensively studied in acute otitis media. In two large collections of cases, the percentages of ‘cure’ or ‘improvement’ ranged from 83% to 98%, side-effects being reported by 1.1%–9.4% of patients [8Hausen TH Weidlich G Schmitt J Safety and efficacy of cefixime in the treatment of respiratory tract infections in Germany.Infection. 1995; 23: S65-S69Crossref PubMed Scopus (6) Google Scholar, 14Wu DH Efficacy and tolerability of cefixime in otitis media.Drugs. 1991; 42: 30-32Crossref PubMed Scopus (13) Google Scholar]. In comparative studies, the overall clinical response of cefixime was found to be comparable with that of amoxicillin, with cefixime and amoxicillin slightly more effective, respectively, in H. influenzae and S. pneumoniae infections [15Owen MJ Anwar R Nguyen HK et al.Efficacy of cefixime in the treatment of acute otitis media in children.AJDC. 1993; 147: 81-85PubMed Google Scholar, 16McLinn SE Randomized, open label, multicenter trial of cefixime compared with amoxicillin for treatment with amoxicillin for treatment of acute otitis media with effusion.Pediatr Infect Dis J. 1987; 6: 997-1001Crossref PubMed Scopus (38) Google Scholar]. In three other trials 1 daily dose of cefixime was found as effective as or more effective than 2 or 5 daily doses of cefaclor, especially in H. influenzae infections [17Kenna MA Bluestone CD Fall P et al.Cefixime vs. cefaclor in the treatment of acute otitis media in infants and children.Pediatr Infect Dis J. 1987; 6: 992-996Crossref PubMed Scopus (44) Google Scholar, 18Baba S Kinoshita H Mori Y et al.A parallel comparative double blind study of cefixime with cefaclor in the treatment for acute suppurative otitis media in children.Jpn J Antibiot. 1987; 40: 1-24Crossref PubMed Scopus (22) Google Scholar, 19Rodriguez WJ Khan W Sait T et al.Cefixime vs. cefaclor in the treatment of acute otitis media in children: a randomized comparative study.Pediatr Infect Dis J. 1993; 12 (in press.)Crossref PubMed Scopus (23) Google Scholar]. Finally, a single daily dose of cefixime was found equally effective as 3 daily doses of amoxicillin/clavulanate in two different studies [20Sunderland R McVey DL Atkin KJ Cefixime versus co-amoxiclav in the treatment of pediatric upper respiratory tract infections and otitis media.Curr Ther Res. 1994; 55: 22-29Abstract Full Text PDF Scopus (6) Google Scholar, 21Gooch WM Philips A Rhoades R et al.Comparison of the efficacy, safety and acceptability of cefixime and amoxicillin/clavulanate in acute otitis media.Pediatr Infect Dis J. 1997; 16: 21-24Crossref PubMed Scopus (26) Google Scholar]. However, adverse events were more frequently observed in patients treated with amoxicillin/clavulanate. Taken together, studies available on cefixime indicate that this third-generation cephalosporin is effective and well tolerated when used in the treatment of upper respiratory tract infections. Especially in streptococcal tonsillopharyngitis and in acute otitis media, cefixime can therefore be considered a suitable alternative to traditional therapy, both in infants and in children and in adults. In patients with acute bronchitis, acute exacerbations of chronic bronchitis and pneumonia, cefixime has been shown to be as clinically effective as amoxicillin, cefaclor, cefalexin, cefuroxime axetil and amoxicillin/clavulanate [22Verghese A Roberson D Kalbfleisch JH et al.Randomized, comparative study of cefixime versus cephalexin in acute bacterial exacerbations of chronic bronchitis.Antimicrob Agents Chemother. 1990; 34: 1041-1044Crossref PubMed Scopus (39) Google Scholar, 23Drehobl M Sahn S Puopolo A et al.A multicenter trial of cefixime and cefuroxime axetil in the treatment of acute LRTI.Infect Med. 1993; 10: 22-28Google Scholar, 24Heinz G Greene S Haddow A et al.Comparison of cefixime and cefaclor in acute LRTI, two randomized studies.Infect Med. 1993; 10: 29-35Google Scholar, 25Kiani P Coulson L Johnson D et al.Comparison of once-daily and twice-daily cefixime regimens with amoxicillin in the treatment of acute lower respiratory tract infections.Curr Ther Res. 1990; 48: 841-852Google Scholar, 26Low DE Scriver SR Evaluation of the in vitro activity of cefixime for its use in switch therapy.Curr Ther Res. 1994; 55: 35-41Abstract Full Text PDF Scopus (12) Google Scholar]. One of the most interesting applications of oral third-generation cephalosporins in the treatment of LRTI is, however, the so-called ‘switch therapy’. From a practical point of view the term ‘switch therapy’ (alternatively ‘streamlining therapy’, ‘sequential therapy’, ‘step-down therapy’ or ‘transitional therapy’) describes the therapeutic practice of changing from intravenous treatment (usually administered for 3 or 4 days) to oral antimicrobial therapy. Changing from intravenous to oral therapy has the potential to reduce antibacterial drug expenditure, which accounts for as much as 30%–40% of hospital pharmacy budgets in the USA and 24.8% in Italy. Oral antimicrobial agents are generally less expensive to purchase and administer than intravenous ones. In addition to acquisition and delivery cost savings, earlier removal of intravenous needles and lines reduces the likelihood of phlebitis and nosocomial sepsis, affords the patient greater comfort and, importantly, may facilitate early discharge from hospital, which ensures a further major cost saving. An antibacterial drug available in both intravenous and oral formulations that produces similar systemic concentrations after administration, represents the ideal intravenous to oral switch regimen. However, no currently available parenteral third-generation cephalosporin is available in oral formulation; thus, when contemplating changing from intravenous therapy with these drugs to oral therapy, a specific oral drug must be used. According to some in vitro studies, for respiratory pathogens other than S. pneumoniae with reduced susceptibility to penicillin, cefixime can be used as a switch agent from cefotaxime or ceftriaxone [27Weingarten SR Riedinger MS Varis G et al.Identification of low-risk hospitalized patients with pneumonia.Chest. 1994; 105: 1109-1115Crossref PubMed Scopus (82) Google Scholar], which are often administered as initial therapy in the treatment of LRTIs. As many as 33% of hospitalized patients with community-acquired pneumonia are potentially suitable for early conversion to oral antimicrobial therapy [28Ramirez JA Srinath L Ahkee S et al.Early switch from intravenous to oral cephalosporins in the treatment of hospitalized patients with community acquired pneumonia.Arch Intent Med. 1995; 155: 1273-1276Crossref PubMed Scopus (199) Google Scholar]. Three studies have evaluated the efficacy of cefixime as oral switch therapy administered after short courses of either ceftizoxime [29Cahn P Grinberg N Kauffman S et al.Cefixime therapy for the treatment of severe acute pneumonias.J Drug Dev. 1993; 6: 59-60Google Scholar, 30Vogel F Bodem G Kunze K et al.Efficacy and tolerance of cefotaxime followed by oral cefixime versus cefotaxime alone in patients with lower respiratory tract infections.Curr Ther Res. 1994; 55: 42-48Abstract Full Text PDF Scopus (18) Google Scholar] or ceftriaxone [29Cahn P Grinberg N Kauffman S et al.Cefixime therapy for the treatment of severe acute pneumonias.J Drug Dev. 1993; 6: 59-60Google Scholar] or cefotaxime [2Klein JO Otitis media.Clin Infect Dis. 1994; 19: 823-833Crossref PubMed Scopus (298) Google Scholar] in patients with LRTIs. According to these studies the intravenous administration of a third-generation cephalosporin followed by oral cefixime is as effective as intravenous treatment of similar overall duration. Furthermore, these studies demonstrate the significant potential of switch therapy to reduce health care costs in selected patients. The study reported by Ramirez [29Cahn P Grinberg N Kauffman S et al.Cefixime therapy for the treatment of severe acute pneumonias.J Drug Dev. 1993; 6: 59-60Google Scholar], for example, shows that by switching to oral cefixime the duration of hospitalization was reduced by 2 days per patient, with savings of US$713 per day and per patient. This accounts for an overall saving of $105 529 for the 74 patients enrolled in the study, estimated on the basis of the cost of hospitalization alone. Finally, switch therapy has not been shown to have a negative impact on the quality of patient care. In conclusion, the assets of cefixime seem mainly to be [6Bluestone CD Review of cefixime in the treatment of otitis media in infants and children.Pediatr Infect Dis. 1993; 12: 75-82Crossref Scopus (19) Google Scholar, 9Peyramond D Tigaud S Brernard Query C et al.Multicenter comparative trial of cefixime and phenoxymethylpenicillin for group A beta-hemolytic streptococcal tonsillitis.Curr Ther Res. 1994; 55: 14-21Abstract Full Text PDF Scopus (25) Google Scholar, 31Quintiliani R Crowe HM Nightingale C Transitional antibiotic therapy.Can J Infect Dis. 1995; 6: 6A-10AGoogle Scholar]: 1. excellent activity in vitro against β-lactamase producing H. influenzae and M. catarrhalis;2. high antibacterial activity against group A β-hemolytic streptococci, high resistance to inactivation by β-lactamases and excellent diffusion into the tonsils;3. demonstrated safety;4. availability in a liquid formulation of high palatability;5. ability to be administered in a single, daily dose;6. potential as the oral drug for switching from intravenous to oral antimicrobial therapy in selected patients with community-acquired pneumonia and other infections, although further studies are certainly required to confirm these favorable preliminary results." @default.
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• W1825697777 title "Oral cephalosporins in airway infections" @default.
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