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Comparative bactericidal activity of cefixime, carumonam, enoxacin and roxithromycin with those of other antibiotics against resistant Haemophilus influenzae including beta-lactam tolerant strains.

One hundred isolates of Haemophilus influenzae including 50 beta-lactamase producing, five ampicillin-resistant non-beta-lactamase producing and five beta-lactam tolerant strains were tested for susceptibility (MICs and MBCs) to ampicillin, aztreonam, carumonam, cefixime, cefaclor, cefamandole, cefotaxime, imipenem, enoxacin, ciprofloxacin, roxithromycin, erythromycin, chloramphenicol, and co-trimoxazole, by a microdilution broth method. Cefotaxime, enoxacin and ciprofloxacin with MIC90 and MBC90 of less than 0.03 mg/l) were the most active antimicrobial agents tested. Cefixime, carumonam, aztreonam, and co-trimoxazole (MIC90 and MBC90 less than 0.25 mg/l) showed good activity against most strains. Roxithromycin and erythromycin had limited antibacterial activity (MIC90, 8 and 4 mg/l respectively). There were no chloramphenicol-resistant strains. Five beta-lactamase-negative strains were resistant to ampicillin, cefaclor and cefamandole but susceptible to other beta-lactams tested. Different patterns of tolerance were observed: four of five tolerant strains were tolerant to ampicillin and cefamandole, three to cefixime, cefaclor and cefotaxime, one to aztreonam. One tolerant strain was a beta-lactamase producer. Two other strains were tolerant only to co-trimoxazole.

Ampicillin↗

The pharmacokinetics of the oral cephalosporins--a review.

The pharmacokinetics of the older and more recent oral cephalosporins are reviewed. With the exception of cefadroxil the older agents (cephalexin, cephradine and cefaclor) have serum elimination half-lives of less than or equal to 1 h and hence have to be administered three to four times daily. The urinary recovery of these agents is high (greater than 80% of oral dose) with the exception of cefaclor (54%). Cefaclor is also chemically unstable. The newer agents can be divided into those that are prodrugs (cefpodoxime proxetil and cefuroxime axetil) and compounds that are absorbed as such (cefixime, cefprozil and ceftibuten). They all have half-lives greater than 1.25 h and can be given once or twice daily. The penetration of these agents into an inflammatory exudate was studied and found to be cefixime 132%, ceftibuten 113%, cefpodoxime 104%, cefuroxime 92% and cefprozil 79% of the serum concentration. The penetration of cefpodoxime and cefixime into the respiratory tract was also studied; the mean percentage bronchial mucosal penetration was 52% for the former and 38% for cefixime. The urinary recovery of these newer agents (with the exception of ceftibuten) tends to be less than that of the earlier agents. There was a relationship between the serum elimination half-life of these agents and the degree of tissue penetration, those agents with longer half-lives penetrating to a greater extent.

Absorption↗

Antibacterial activity of oral antibiotics against community-acquired respiratory pathogens from three European countries.

Antimicrobial resistance is universally recognized as a major problem. A European resistance survey was established to monitor the activity of widely used oral antibiotics against common respiratory tract pathogens. Studies were conducted in Italy, Spain and Austria to monitor resistance patterns among respiratory Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes, Staphylococcus aureus and Klebsiella pneumoniae to amoxicillin, co-amoxiclav, penicillin, cefaclor, cefadroxil, cefalexin, cefprozil, cefuroxime, cefixime, ceftibuten, cefpodoxime, clarithromycin and azithromycin (the antibiotics tested varying slightly from country to country). Minimum inhibitory concentrations were determined using the NCCLS-recommended broth microdilution method. Among the antibiotics tested, cefpodoxime, an oral cephalosporin, was remarkably active against the major respiratory pathogens in all three countries. Cefpodoxime was more potent than cefaclor, cefixime and ceftibuten against pneumococci, especially against strains with decreased sensitivity to penicillin, and more active than cefaclor and cefuroxime against Gram-negative respiratory pathogens. Pneumococci and staphylococci displayed a very high level of in vitro macrolide resistance. These data indicate that cefpodoxime represents an appropriate choice in the treatment of community-acquired respiratory tract infection in the three countries surveyed.

Administration, Oral↗

Resistance pattern of middle ear fluid isolates in acute otitis media recently treated with antibiotics.

BACKGROUND: Little information is available about the effect of antibiotic treatment on the prevalence and MIC of the subsequently isolated pathogens in cases of acute otitis media (AOM) failing a course of antibiotic therapy. This information is important, particularly regarding the effectiveness of the oral antibiotics used in children failing initial therapy. PATIENTS AND METHODS: One hundred eighty-one children with culture-positive AOM were prospectively studied between October, 1995, and July, 1996. Sixty-three (35%) patients received various antibiotics for variable periods during the 14 days preceding enrollment. RESULTS: A total of 94 Streptococcus pneumoniae (Pnc) and 113 Haemophilus influenzae (Hi) were isolated. Thirty-eight Pnc and 35 Hi were isolated in the 63 patients with recently treated AOM. Pnc as a single isolate was more prevalent in patients recently treated with antibiotics (27 of 63, 43%) than among those not recently treated (32 of 118, 27%, P = 0.047). The MIC50 values of penicillin, cefaclor and cefuroxime axetil for Pnc were significantly higher in the pneumococci isolated from patients recently treated than among those isolated from patients not recently treated with antibiotics (0.38, 3 and 0.75 microg/ml vs. 0.094, 0.38 and 0.12 microg/ml, respectively). Seventy-nine percent of Pnc isolates in the recently treated group had MIC for penicillin of >0.1 microg/ml vs. only 47% in those not recently treated (P < 0.05). The respective figures for MIC >0.5 microg/ml of cefaclor were 79% vs. 41% for the recently treated and not recently treated groups (P < 0.001); cefuroxime MIC >0.5 microg/ml was found in 61 and 25%, respectively (P = 0.001). CONCLUSIONS: Pneumococcus is more prevalent in AOM after a recent antibiotic treatment, and the MIC of the commonly used beta-lactam drugs for Pnc is considerably higher in this setting. In view of our data, the use of oral cephalosporins like cefaclor or cefuroxime as second line drugs in the treatment of unresponsive AOM, particularly in regions where resistant PNC is prevalent, should be reconsidered.

Acute Disease↗

Comparative in vitro activity and beta-lactamase stability of FR 17027, a new orally active cephalosporin.

FR 17027, a new orally absorbed cephalosporin ester, inhibited group A and B streptococci and Streptococcus pneumoniae at less than or equal to 0.1 micrograms/ml, which is similar to the inhibition concentration of amoxicillin and cefaclor, and was more active than cephalexin. It was less active (MIC, 25 micrograms/ml) against staphylococci than was cephalexin, and it did not inhibit Streptococcus faecalis or Listeria monocytogenes. FR 17027 inhibited beta-lactamase-producing isolates of Neisseria gonorrhoeae, Haemophilus influenzae, and Branhamella catarrhalis at less than 0.1 micrograms/ml and was more active than cefaclor or cephalexin against these bacteria. FR 17027 inhibited Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Klebsiella oxytoca, Providencia stuartii, Providencia rettgeri, and Citrobacter diversus at less than or equal to 1 microgram/ml, including isolated resistant to amoxicillin, cephalexin, and cefaclor, but it was less active than ceftizoxime. Some strains of Enterobacter cloacae, Enterobacter agglomerans, Citrobacter freundii, and Enterobacter aerogenes were resistant (MIC, greater than 25 micrograms/ml). FR 17027 did not inhibit Pseudomonas aeruginosa, other Pseudomonas species, Acinetobacter species, or Bacteroides species. Activity was minimally affected by growth conditions. FR 17027 was not hydrolyzed by the common beta-lactamases present in many of the pathogens causing respiratory and urinary tract infections in outpatients.

Amoxicillin↗

Antimicrobial spectrum of Ro 15-8074/001, a new oral cephalosporin.

The activity of Ro 15-8074/001 was compared with that of cefaclor, amoxicillin-clavulanic acid, trimethoprim-sulfamethoxazole, norfloxacin, and ceftriaxone against 225 clinical isolates. It was more active than cefaclor, amoxicillin-clavulanic acid, and trimethoprim-sulfamethoxazole against members of the family Enterobacteriaceae and Haemophilus influenzae and had activity similar to that of cefaclor against nonenterococcal streptococci. It was not usefully active against Pseudomonas aeruginosa, Streptococcus faecalis, or most isolates of staphylococci.

Anti-Bacterial Agents↗

Disk diffusion susceptibility testing of Branhamella catarrhalis with ampicillin and seven other antimicrobial agents.

A total of 74 clinical isolates of Branhamella catarrhalis were characterized with respect to their ampicillin, amoxicillin-clavulanate, cephalothin, cefaclor, erythromycin, tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole MICs and zones of inhibition. Disk diffusion tests were performed according to the guidelines of the National Committee for Clinical Laboratory Standards with two different media (Mueller-Hinton agar and chocolate Mueller-Hinton agar) and plates incubated under two atmospheric conditions (ambient air and 5 to 7% CO2). Optimum disk diffusion test results were obtained with Mueller-Hinton agar plates incubated in ambient air with all eight antimicrobial agents. On the basis of comparisons of MICs versus zones of inhibition, the following zone diameter interpretive criteria were defined for testing B. catarrhalis with disks containing 10 micrograms of ampicillin: greater than or equal to 38 mm, susceptible; 20 to 37 mm, moderately susceptible; less than or equal to 19 mm, resistant. The respective MIC correlates were less than or equal to 0.06, 0.125 to 0.5, and greater than or equal to 1.0 micrograms/ml. Because of the absence of frankly resistant test organisms, it was not possible to make definitive recommendations pertaining to disk diffusion tests with amoxicillin-clavulanate, cephalothin, cefaclor, erythromycin, tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole. Evidence is presented, however, which suggests that the current National Committee for Clinical Laboratory Standards disk diffusion interpretive criteria for nonfastidious bacteria can be applied to B. catarrhalis, at least as they pertain to the susceptible category with cephalothin, amoxicillin-clavulanate, erythromycin, tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole. With cefaclor, a zone diameter of greater than or equal to 21 mm was determined to adequately define the susceptible category.

Ampicillin↗

Influence of storage and susceptibility test conditions on stability and activity of LY163892 and four other cephalosporins.

A new carbacephem analog of cefaclor, LY163892, was examined along with four other cephalosporins for chemical stability and for antibacterial activity under a variety of susceptibility test conditions. LY163892 was found to be markedly more stable than cefaclor during storage at 4 and 35 degrees C in human serum, human urine, and various bacteriological media. Under these conditions, LY163892 demonstrated stability equal or superior to the stabilities of cephalexin, cephalothin, and cefuroxime. Broth and agar dilution susceptibility tests did not reveal significant differences in LY163892 activity in a variety of test media, although LY163892 MICs were somewhat higher in Mueller-Hinton chocolate agar or Trypticase soy broth (BBL Microbiology Systems, Cockeysville, Md.) than in other media. The activity of LY163892 against selected pathogens was only slightly influenced by the increased or decreased pH of the test medium, in a manner similar to that of the other cephalosporins tested. Thus, the carbacephem structure of LY163892 appears to represent a more stable cephalosporin than cefaclor, while retaining a similar antimicrobial spectrum.

Bacteria↗

Disk diffusion versus broth microdilution susceptibility testing of Haemophilus species and Moraxella catarrhalis using seven oral antimicrobial agents: application of updated susceptibility guidelines of the National Committee for Clinical Laboratory Standards.

Susceptibility testing of Haemophilus species and Moraxella catarrhalis is medium and inoculum dependent. Seven oral agents, ampicillin, amoxicillin-clavulanic acid, cefaclor, loracarbef, cefuroxime-axetil, cefixime, and erythromycin, were tested against 400 beta-lactamase-positive and -negative clinically significant respiratory strains of Haemophilus species and 100 strains of M. catarrhalis. Sources of the strains included teaching and regional hospitals and a private laboratory. All strains were tested by broth microdilution and disk diffusion in haemophilus test medium for Haemophilus species and Mueller-Hinton broth and agar for M. catarrhalis. Appropriate National Committee for Clinical Laboratory Standards (NCCLS) standards were followed. For Haemophilus species, by disk diffusion and broth microdilution, respectively, 27 and 27% of strains were resistant to ampicillin, 37 and 5% were resistant to erythromycin, 3 and 0.5% were resistant to cefaclor, 2 and 0.5% were resistant to loracarbef, and 0% were resistant to cefuroxime-axetil, cefixime, and amoxicillin-clavulanic acid. beta-Lactamase-negative ampicillin-resistant strains were not observed. Of M. catarrhalis strains, 56% were resistant to ampicillin by disk diffusion and 95% were resistant by broth microdilution. This species was susceptible to all other agents tested by either method. The disagreements between disk diffusion results and MICs for cefaclor, ampicillin, cefuroxime, and loracarbef that occurred with use of the 1990 NCCLS tables were resolved when the 1992 NCCLS tables were used.

Administration, Oral↗

In vitro activity of cefixime (CL284635) and other antimicrobial agents against Haemophilus isolates from pediatric patients.

In vitro activity of cefixime, an experimental oral third-generation cephalosporin and 7 other antimicrobials (ampicillin, augmentin, trimethoprim/sulfamethaxazole, cefamandole, cefotaxime, cefuroxime, and cefaclor) were determined for 150 isolates of Haemophilus obtained from pediatric patients. All (109) non-typeable H. influenzae isolates were sensitive to cefixime and cefotaxime. All (18) isolates of H. parainfluenzae were sensitive to cefotaxime, cefuroxime, cefamandole, cefaclor, and augmentin; 17/18 isolates were sensitive to cefixime. All (23) isolates of H. influenzae-b were sensitive to cefixime, cefotaxime, cefamandole, cefuroxime, cefaclor, and augmentin. Only 10/23 were sensitive to tri/sulfa. 137 of 150 (91.3%) isolates had MBCs equivalent to their MICs for cefixime, compared to 149/150 (99.3%) isolates for cefotaxime. Approximately 95% (143/150) of isolates tested had MICs of less than or equal to 0.06 microgram/ml for cefixime. These data demonstrate that in vitro cefixime has good activity against Haemophilus isolates and it is very similar to the activity of cefotaxime.

Anti-Bacterial Agents↗

Comparable evaluation of orally active beta-lactam compounds in ampicillin-resistant gram-positive and gram-negative rods: role of beta-lactamases on resistance.

The antibacterial activity of the recently developed cephems cefixime and cefetamet-pivoxyl was evaluated in 408 gram-positive and gram-negative rods, all isolated recently from clinical specimens, and compared to that of other orally active agents such as ampicillin, amoxycillin + clavulanic acid, cefaclor, cefuroxime-axetil and to ceftriaxone. With regard to ampicillin-resistant Enterobacteriaceae ceftriaxone proved to be the most active agent, followed by cefixime and cefetamet, whereas cefuroxime was less active. Cefaclor and amoxycillin + claculanic acid were active against ampicillin-resistant Escherichia coli, Klebsiella pneumoniae, and Proteus ssp. isolates. All beta-lactam compounds exhibited poor activity against Acinetobacter anitratus isolates, but were highly active against Haemophilus influenzae with the exception of cefaclor. Both cefixime and cefetamet were poorly active against Staphylococcus aureus, but highly active against beta-hemolytic streptococci. Moreover, both compounds remained unaffected by the production of plasmid-mediated beta-lactamases such as the TEM or OXA enzymes. Resistance to both agents was observed in Enterobacteriaceae that produced large amounts of chromosomally mediated enzymes; their affinity to the class I enzyme from Enterobacter cloacae was somewhat lower than that of other third-generation cephalosporins. However, in contrast with these agents breakdown of cefixime and cefetamet by a class IIIa enzyme form Proteus vulgaris was marginal. In methicillin-resistant S. aureus isolates there was a complete cross-resistance between all beta-lactam compounds included in this study.

Ampicillin Resistance↗

Clinical experience with 1000 patients treated with cefetamet pivoxil.

Clinical studies have been carried out world-wide on cefetamet pivoxil, a new orally active cephalosporin. This paper reports on the first 1000 patients treated with the antibiotic; another 505 patients received standard antibiotics, mainly cefadroxil and cefaclor, for comparison. The results show that single doses of 1500 and 1200 mg cefetamet pivoxil were fully effective in gonorrhoea. Comparative trials in uncomplicated urinary tract infection indicate a significant superiority of a single dose of 2 g cefetamet pivoxil (n = 158; 90.0% cure) versus 2 g cefadrox (n = 162; 77.0% cure). In complicated urinary tract infections, a comparable outcome was achieved with a single daily dose of 2 g cefetamet pivoxil for 10 days (n = 99; 90% cure) and 1 g cefadroxil twice daily for 10 days (n = 98; 76.5% cure). The clinical response rate in acute exacerbation of chronic bronchitis was 89.4% in the group receiving cefetamet pivoxil (136 patients) and 83% in the cefaclor-treated group (n = 122). Treatment with 1000 or 2000 mg cefetamet pivoxil achieved a (bacteriological) success rate of 96% compared to 95% with cefaclor in acute ear, nose and throat-infections (n = 91). Overall, based on 894 isolated pathogens prior to therapy, the bacteriological response rate was 90% and it would appear that in vivo the spectrum of this cephalosporin covers a wide range of Gram-negative and Gram-positive pathogens, including urinary pathogens, but excluding Enterococci and Pseudomonas. Cefetamet pivoxil proved to be well tolerated. Mild to moderate adverse events were reported in 7.1% of patients but only 2 of the 1000 patients treated with cefetamet pivoxil were withdrawn because of diarrhoea, which subsided rapidly. There were no clinically relevant deviations in laboratory parameters.

Adult↗

Isolation of Staphylococcus aureus and antibiotic-resistant Staphylococcus aureus from residential indoor bioaerosols.

OBJECTIVE: In this study we evaluated the levels of Staphylococcus aureus and antibiotic-resistant S. aureus in colony-forming units (CFU) per cubic meter of air. DESIGN: We used Andersen two-stage samplers to collect bioaerosol samples from 24 houses in El Paso, Texas, using tryptic soy agar as the collection media, followed by the replicate plate method on Chapman Stone selective medium to isolate S. aureus. The Kirby-Bauer disk diffusion method was used to determine antibiotic resistance to ampicillin, penicillin, and cefaclor, which represent two distinct classes of antibiotics. RESULTS: The average recovered concentration of respirable heterotrophic organisms found outside each home was 345.38 CFU/m3, with an average of 12.63 CFU/m3 for S. aureus. The average recovered concentration of respirable heterotrophic organisms found inside each home was 460.23 CFU/m3, with an average of 15.39 CFU/m3 for S. aureus. The respirable S. aureus recovered from inside each home had an average resistance of 54.59% to ampicillin and 60.46% to penicillin. Presence of cefaclor-resistant and of multidrug-resistant S. aureus was the same, averaging 13.20% per house. The respirable S. aureus recovered from outside each home had an average resistance of 34.42% to ampicillin and 41.81% to penicillin. Presence of cefaclor-resistant and of multidrug-resistant S. aureus was the same, averaging 13.96% per house. CONCLUSIONS: This study indicates that antibiotic-resistant bioaerosols are commonly found within residential homes. Our results also suggest that resistant strains of airborne culturable S. aureus are present in higher concentrations inside the study homes than outside the homes.

Air Microbiology↗

Otitis media-related antibiotic prescribing patterns, outcomes, and expenditures in a pediatric medicaid population.

BACKGROUND: Treatment of otitis media is the most frequent reason for administering antibiotics to children in the United States. However, only limited data are available on medical effectiveness of antibiotic prescribing patterns for otitis media and their associated expenditures or the factors that influence antibiotic prescribing. METHODS: The study population consisted of 131 169 children during 1991 and 157 065 children during 1992 who were </=13 years of age and enrolled in Colorado's fee-for-service Medicaid program. Among these children, 5127 (1991) and 7254 (1992) were enrolled in the cohort treated for a "new" episode of acute otitis media. An analysis using this cohort was performed to document the antibiotics used to treat a new episode of acute otitis media, factors influencing antibiotic selection, and the short-term outcomes of therapy. An analysis using the entire Medicaid population was performed to document the annual use of antibiotics for otitis, the associated antibiotic expenditures, and factors influencing antibiotic selection. RESULTS: In the cohort analysis, office-based physicians prescribed second- and third-generation cephalosporins more often than did physicians in other settings (17% vs 9.7% and 11.8%), whereas hospital clinics prescribed trimethoprim plus sulfamethoxazole more frequently than did office-based physicians (19.2% vs 7.1% and 10.9%). Family physicians prescribed second- and third-generation cephalosporins more often than did pediatricians (16.6% vs 12.3%) but trimethoprim plus sulfamethoxazole and erythromycin plus sulfisoxazole less often than did pediatricians (10.5% vs 17%). The average rate of prescribing a second course of antibiotics within 24 days after initial antibiotic treatment of a new acute otitis media episode was 11.6% when less expensive antibiotics (amoxicillin, trimethoprim plus sulfamethoxazole, or erythromycin plus sulfisoxazole) were prescribed, and 13.2% when more expensive antibiotics (cefaclor, amoxicillin plus clavulanate, or cefixime) were prescribed. The average adverse drug reaction rate was 5.9% when less expensive antibiotics were prescribed, compared with 6.1% when more expensive antibiotics were prescribed. In each of the two study years, amoxicillin accounted for almost half of the total antibiotic fills but only 9% to 10% of the expenditures. Low-cost antibiotics (amoxicillin, trimethoprim plus sulfamethoxazole, and erythromycin plus sulfisoxazole) were prescribed for 66% to 67% of the total fills and accounted for 21% of the total projected expenditures. More expensive antibiotics (cefaclor, cefixime, amoxicillin plus clavulanate) prescribed for 30% of the fills generated 76% to 77% of expenditures. Cefaclor, prescribed for 17% to 18% of the total fills, generated 43% to 45% of total antibiotic expenses. CONCLUSIONS: The findings of this study document a preference for amoxicillin as the initial antibiotic for a new episode of acute otitis media. Although there was a wide variation in the selection of antibiotics to treat otitis, the more expensive antibiotics were not associated with better outcomes. This wide variation has important financial implications because of differences in antibiotic costs. Changes in prescribing patterns among initially uncomplicated children that reduce the use of high-cost antibiotics could reduce expenditures substantially without compromising short-term outcomes.

Acute Disease↗

Cefixime. A review of its antibacterial activity. Pharmacokinetic properties and therapeutic potential.

Cefixime, previously designated FK027, FR17027 and CL284635, is an orally active cephalosporin with a broad spectrum of antibacterial activity in vitro. It is particularly active against many Enterobacteriaceae, Haemophilus influenzae. Streptococcus pyogenes, Streptococcus pneumoniae and Branhamella catarrhalis, and is resistant to hydrolysis by many beta-lactamases. Cefixime has little activity against Staphylococcus aureus and is inactive against Pseudomonas aeruginosa. Cefixime is distinguished by its 3-hour elimination half-life which permits twice daily, or in many instances once daily, administration. Comparative trials, though few, indicate that the clinical and bacteriological efficacy of cefixime 200 to 400mg daily administered as a single dose or in 2 divided doses, is comparable with that of multiple daily doses of co-trimoxazole (trimethoprim + sulphamethoxazole) or amoxycillin in acute uncomplicated urinary tract infection, with that of amoxycillin, amoxycillin/clavulanic acid and cefaclor in acute lower respiratory tract infections, and with that of amoxycillin and cefroxidine in adult patients with acute tonsillitis or pharyngitis. Several comparative trials in children with acute otitis media demonstrate the similar effectiveness of cefixime 8 mg/kg daily (in 2 divided doses, or as a single daily dose), cefaclor 20 to 40 mg/kg daily and amoxycillin 40 mg/kg daily in 3 divided doses. The most frequently reported adverse effects, diarrhoea and stool changes, are usually mild to moderate in severity, transient, and mostly occur in the first few days of treatment with cefixime. Thus, cefixime is an effective orally active cephalosporin with a relatively long elimination half-life permitting a simplified treatment regimen. It is a suitable alternative to cefaclor or amoxycillin in acute otitis media and acute upper and lower respiratory tract infections, and to amoxycillin or co-trimoxazole in acute uncomplicated urinary tract infections.

Anti-Infective Agents↗

Antibiotic susceptibility of upper respiratory tract pathogens in Sweden: a seven year follow-up study including loracarbef. Swedish Respiratory Tract Study Group.

The antibiotic susceptibility of Haemophilus influenzae, Moraxella catarrhalis, Streptococcus pyogenes and Streptococcus pneumoniae was investigated in five different geographical areas of Sweden in 1990 and compared with results from similar investigations performed in 1983 and 1986. Tests on 100 isolates per species and laboratory were performed by the disk diffusion method, and 10% of the strains plus all resistant ones were sent to the central laboratory for determination of MICs of ampicillin, phenoxymethylpenicillin, cefaclor, loracarbef, erythromycin, tetracycline and trimethoprim/sulfamethoxazole. Beta-lactamase production was found in 7% of H. influenzae and 71% of M. catarrhalis, and reduced susceptibility to penicillin in 3% of S. pneumoniae. Low frequencies (1-3%) of tetracycline resistance were found in H. influenzae and in the 2 streptococcal species, in which also less than 1% of the strains were resistant to erythromycin. Resistance to trimethoprim/sulfamethoxazole occurred in 7% (range 3-14%) of H. influenzae and in 3% of S. pneumoniae. Cefaclor was active against all streptococci except against S. pneumoniae with reduced susceptibility to penicillin. It was active against beta-lactamase negative strains of M. catarrhalis but had, according to the SIR-system, intermediate activity against H. influenzae. Loracarbef was twice as active as cefaclor against H. influenzae but equally active against the 3 other species tested.

Cephalosporins↗

Antimicrobial resistance of invasive Streptococcus pneumoniae in Slovenia, 1993-1995. The Slovenian Meningitis Study Group.

The susceptibility of 108 Streptococcus pneumoniae strains isolated from normally sterile body sites during 1993-1995 in Slovenia has been studied. Overall resistance to penicillin, erythromycin, trimethoprim-sulfamethoxazole, cefuroxime, cefaclor and chloramphenicol was 16.6, 0.9, 26.8, 0, 4.5 and 4.6%, respectively. All penicillin-resistant isolates (intermediate resistance) were susceptible to cefotaxime, ceftriaxone and vancomycin. Isolates less susceptible to penicillin were also significantly less sensitive to chloramphenicol, cefaclor and trimethoprim-sulfamethoxazole than penicillin-sensitive strains. Pneumococci isolated in children were significantly (p < 0.05) more resistant to trimethoprim-sulfamethoxazole than those isolated in adults. The study demonstrated moderate resistance rate of S. pneumoniae to penicillin and trimethoprim-sulfamethoxazole and a low-level resistance rate to erythromycin, cefaclor and chloramphenicol. No straightforward correlation between overall consumption of antibiotics and antimicrobial resistance was found.

Adolescent↗

Pharmacoeconomic analysis of selected antibiotics in lower respiratory tract infection.

An interactive pharmacoeconomic model was designed to evaluate the effects of clinical response and adverse drug events on the comparative cost and cost-effectiveness of a relatively new antibiotic, clarithromycin, compared with those of six other antibiotics used to treat community-acquired lower respiratory tract infection. The cost and cost-effectiveness analyses were based don 12 randomized, double-blind, controlled clinical trials conducted between 1987 and 1992 in regionally distributed outpatient clinics in the United States. The trials enrolled a total of 2377 patients. Of the 2377, 1102 patients were treated for acute exacerbation of chronic bronchitis, 591 for pneumonia, and 201 for either of the two conditions. Safety data for one of the antibiotics was obtained from a trial of patients with sinusitis (N = 483). The antibiotics included in the analysis were amoxicillin/clavulanate, ampicillin, cefaclor, cefixime, cefuroxime, clarithromycin, and erythromycin. The main outcome measures were the costs of resources to achieve a clinical response, costs related to managing adverse drug events, and costs of antibiotic treatment from the perspective of managed care. The mean total cost per episode ranged from approximately $137 to $267. The drug acquisition cost typically contributed a small amount to the overall cost. For the cost-effectiveness analysis, in which complication-free cure was used as a proxy for patient satisfaction, the range of mean cost per complication-free cure varied from approximately $307 for clarithromycin to $612 for cefaclor. When ranked from most to least cost-effective, the order was as follows: clarithromycin, cefixime, amoxicillin/clavulanate, erythromycin, cefuroxime, ampicillin, and cefaclor. The costs associated with clinical management (including treatment failure) and managing adverse drug events significantly contribute to the total cost and cost-effectiveness of antibiotics in the outpatient setting. Cost-effectiveness analyses are valuable in analyzing the various costs associated with the treatment of lower respiratory tract infection (acute exacerbation of chronic bronchitis or pneumonia) and may be useful tools for physicians managing patients, members of pharmacy and therapeutics committees developing formularies, and medical staff implementing practice guidelines.

Anti-Bacterial Agents↗