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[Sensitivity of Haemophilus influenzae isolates in Spain to 17 oral antibiotics].

INTRODUCTION: The objective of this study was to assess the sensitivity of 400 strains of Haemophilus influenzae isolated in 21 Spanish laboratories in 1999 to 17 oral antibiotics.Methods. An agar dilution method in HT medium was used for sensitivity testing; interpretation of the results followed NCCLS criteria. RESULTS: Percentages of isolates susceptible to the antibiotics tested were as follows: ampicillin 59.5%, amoxicillin/clavulanate 99.2%, loracarbef 66.2%, cefprozil 70.2%, cefaclor 76.2%, cefuroxime 95%, ceftibuten 100%, cefpodoxime 100%, cefixime 100%, rifampin 99.8%, tetracycline 98.2%, chloramphenicol 99.2%, nalidixic acid 97.5%, ciprofloxacin 100%, trovafloxacin 100%, clarithromycin 74%, and azithromycin 100%. CONCLUSIONS: Geographic distribution of sensitivity rates was not homogeneous for some antibiotics. Around 24% of strains were betalactamase producers, requiring higher MICs of antibiotics such as loracarbef, cefprozil and cefaclor than non betalactamase producers. Nevertheless MICs of ceftibuten, cefpodoxime and cefixime were similar in both betalactamase producers and non-producers. Five strains (1.25%) were beta -lactamase (2), but resistant to ampicillin (MIC > or = 8 mg/L) and to amoxicillin/clavulanic acid (MIC > or = 4/2 mg/L). Only three strains showed intermediate sensitivity to chloramphenicol. These strains and four others were inhibited with > or = 4 mg/L of tetracycline. Only one strain was resistant to tetracycline (MIC: 64 mg/L) and to rifampin (MIC: 256 mg/L). All strains were sensitive to azithromycin (MICs < or = 4 mg/L) and all were sensitive to ciprofloxacin and trovafloxacin (MICs < or = 0.5 mg/L). However, ten strains (2.5%) were resistant to nalidixic acid (MIC > or = 4 mg/L).

Administration, Oral↗

In vitro susceptibility of recent clinical isolates of pneumococci to the investigational cephalosporin cefditoren.

From February to June 2000, 2,597 isolates of Streptococcus pneumoniae were prospectively collected from 146 clinical laboratories across the United States (US) and tested to evaluate the in vitro activity of cefditoren, an investigational oral cephalosporin. In all, 2,492 isolates (96.0%) had a cefditoren MIC of 0.5 microg/mL or less, 74 isolates (2.8%) had an MIC of 1 microg/mL, 30 isolates (1.2%) had an MIC of 2 microg/mL, and 1 isolate (<0.1%) had an MIC of 4 microg/mL. Among the beta-lactams tested, the rank order of potency (MIC(90,) microg/mL) was cefditoren (0.5) > ceftriaxone (1) > amoxicillin-clavulanate (2) > cefuroxime (4) > cefprozil (8). Penicillin-resistant isolates (n = 443; 17.1%) were inhibited by lower concentrations (MIC(90,) microg/mL; MIC range,) of cefditoren (1; 0.03-4) than ceftriaxone (2; 0.25- > 2), amoxicillin-clavulanate (8; 0.5- > 8), cefuroxime (16; 2- > 16), and cefprozil (32; 2- > 32). Cefditoren MIC(90)s against cefuroxime-resistant (n = 640) and ceftriaxone-resistant (n = 89) isolates were 1 and 2 microg/mL, respectively. All isolates with reduced susceptibility to cefditoren (MIC, 2 or 4 microg/mL; n = 31) were resistant to penicillin, cefuroxime, and ceftriaxone. The potent in vitro activity of cefditoren against a recent US collection of pneumococci as demonstrated in this study supports its continued development for oral empiric therapy in outpatients with respiratory tract infections.

Cephalosporins↗

A 1994-95 survey of Haemophilus influenzae susceptibility to ten orally administered agents. A 187 clinical laboratory center sample in the United States.

During August, 1994 to April, 1995, a total of 2278 clinical isolates of Haemophilus influenzae were obtained from 187 clinical laboratories in the United States (U.S.). The vast majority of these isolates (75%) were from respiratory sites, and the remaining organisms were from blood, ear, eye, and spinal fluid sources. The overall rate of beta-lactamase production and ampicillin resistance was 36%. The antimicrobial susceptibility of isolates was determined by reference broth microdilution testing against ten orally administered agents. MIC values were compared according to 12 geographical regions, inpatient or outpatient status, gender, and eight age groupings. Modest and occasionally significant differences were observed: 1) greater numbers of beta-lactamase-producing strains among outpatients, in males, in the mid-Atlantic region, and in children < or = 12 years of age; 2) lower prevalence of beta-lactamase-producing isolates in the Southeast and Pacific regions; 3) cefaclor, cefprozil, and loracarbef activity was lowest among the younger children (< or = six years); and 4) macrolide in vitro efficacy was lowest in patients > 50 years of age and in three eastern regions. Overall, more than 99% of the strains were susceptible to amoxicillin/clavulanic acid, cefixime, and cefpodoxime (e.g., widest potential clinical use). Susceptibilities using National Committee for Clinical Laboratory Standards (NCCLS) breakpoint criteria for the other agents were: 96.6% to cefuroxime, 86.5% to loracarbef, 84.0% to clarithromycin, 81.8% to cefaclor, and 80.7% to cefprozil. Non-beta-lactamase mechanisms of resistance to ampicillin were rare (0.2%) or episodic and were attributed to altered penicillin-binding proteins. Although there is an increased prevalence of beta-lactamase production among H. influenzae isolates compared to prior years, four beta-lactams remain highly active (> 95% susceptibility) against contemporary strains of H. influenzae. Other monitored compounds seem to have declined in spectrum and surveillance trials for resistance among H. influenzae isolates should continue in an effort to identify trends in the U.S.

Adult↗

In vitro activity of oral antimicrobial agents against clinical isolates of Pasteurella multocida.

Pasteurella multocida causes a wide variety of infections and is the most common localized soft tissue infection after animal bite injuries. Penicillin or amoxicillin has been considered agent of choice for therapy. Reported beta-lactamase production by some isolates, the therapeutic dilemma of the penicillin allergic patient, and the polymicrobial nature of some infections led to this study of alternate antimicrobial agents. The in vitro activity of ampicillin, amoxicillin/clavulanate, cefprozil, cefuroxime, erythromycin, clarithromycin, trimethoprim/sulfamethoxazole, ciprofloxacin, and tetracycline were compared to penicillin against 73 geographically diverse isolates of P. multocida from human infections collected since 1991. MIC90 (microgram/mL) were as follows: penicillin < or = 0.06; ampicillin < or = 0.5; amoxicillin/clavulanate < or = 0.5; cefaclor 1.0; cefprozil 1.0; cefpodoxime 0.06; cephalothin 2.5; cefuroxime < or = 0.25; erythromycin 2.0; azithromycin 1.0; clarithromycin 4.0; trimethoprim/sulfamethoxazole < or = 0.5/9.5; ciprofloxacin < or 0.25; tetracycline < or = 2.0. No beta-lactamase producing isolates were found in this study. This in vitro study has identified alternate oral agents to penicillins that may be appropriate for therapy of P. multocida infections.

Anti-Bacterial Agents↗

A 1997-1998 national surveillance study: Moraxella catarrhalis and Haemophilus influenzae antimicrobial resistance in 34 US institutions.

From November 1, 1997 to April 30, 1998, 726 Moraxella catarrhalis isolates and 1529 Haemophilus influenzae isolates were obtained from 34 medical centres throughout the United States. Rates of beta-lactamase production were 94.6% among M. catarrhalis and 31.1% among H. influenzae strains. Susceptibility rates of M. catarrhalis isolates to selected antimicrobial agents were greater than 99% for amoxycillin-clavulanate, cefixime, cefpodoxime, cefuroxime, cefaclor, loracarbef, clarithromycin, azithromycin, chloramphenicol and tetracycline, 97.8% for cefprozil, 50.4% for trimethoprim-sulphamethoxazole and 28.1% for ampicillin. Of the antimicrobials tested against H. influenzae, the only agents with susceptibility rates below 96% were loracarbef (87.6%), cefprozil (83.4%), cefaclor (82.7%), trimethoprim-sulphamethoxazole (67.3%) and ampicillin (64.7%). The clarithromycin susceptibility rate was 67.4% but this agent was not tested in the presence of its 14-OH metabolite.

Adolescent↗

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↗

Distribution of Streptococcus pneumoniae resistant to penicillin in the USA and in-vitro susceptibility to selected oral antibiotics.

Surveillance by 33 laboratories in 19 states during a 4 1/2 month period between December 1993 and April 1994 found that 263 of 1627 (16.2%) isolates of Streptococcus pneumoniae were resistant to penicillin. One hundred and seventy (10.4%) isolates were determined to be intermediately resistant to penicillin (MICs 0.1-1.0 mg/L and 93 (5.7%) were found to be highly resistant to penicillin (MICs > 2.0 mg/L). MIC90s for intermediately penicillin resistant strains were: amoxycillin/clavulanate 2.0 mg/L, cefaclor 64 mg/L, cefixime 32 mg/L, cefprozil 8 mg/L and loracarbef 128 mg/L. MIC90s for highly penicillin resistant strains were: amoxycillin/clavulanate 4.0 mg/L, cefaclor > or = 128 mg/L cefixime 64 mg/L, cefprozil 32 mg/L and loracarbef > or = 128 mg/L.

Administration, Oral↗

Global distribution of TEM-1 and ROB-1 beta-lactamases in Haemophilus influenzae.

OBJECTIVES: To determine the global distribution of TEM-1 and ROB-1 beta-lactamases in Haemophilus influenzae isolated from patients with community-acquired respiratory tract infection during the first 4 years of the PROTEKT study (1999-2003). To investigate the activities of commonly used antibiotics against these isolates. METHODS: For 14 870 H. influenzae, MIC testing was performed using NCCLS broth microdilution methodology. For 2225 beta-lactamase-positive (BLP) H. influenzae, TEM-1 and ROB-1 genes were detected using a Taqman PCR method. RESULTS: beta-Lactamase positivity was 15.0% overall but varied greatly by country (<5% in several countries to 67.9% in Taiwan). Prevalences of TEM-1 and ROB-1 BLP H. influenzae were 93.7% and 4.6%, respectively, however almost all ROB-1 isolates were found in Canada, the USA and Mexico. ROB-1 isolates (n = 102) were less susceptible against cefaclor (29.4% versus 87.6%) and cefprozil (42.2% versus 91.9%) than TEM-1 (n = 2085) isolates. Differences in susceptibility rates for chloramphenicol, co-trimoxazole and tetracycline were also found between the two groups. CONCLUSIONS: The ROB-1 beta-lactamase was found almost exclusively in North America and was more active against cefaclor and cefprozil than the TEM-1 beta-lactamase.

Global Health↗

Susceptibilities of Streptococcus pneumoniae and Haemophilus influenzae to 10 oral antimicrobial agents based on pharmacodynamic parameters: 1997 U.S. Surveillance study.

The susceptibilities of Streptococcus pneumoniae (1,476 strains) and untypeable Haemophilus influenzae (1,676 strains) to various oral beta-lactam, macrolide-azalide, and fluoroquinolone antimicrobial agents were determined by broth microdilution. Organisms were isolated from specimens obtained from outpatients in six geographic regions of the United States. MIC data were interpreted according to pharmacodynamically derived breakpoints applicable to the oral agents tested. Among H. influenzae strains, 41.6% were beta-lactamase positive. Virtually all H. influenzae strains were susceptible to amoxicillin-clavulanate (98%), cefixime (100%), and ciprofloxacin (100%), while 78% were susceptible to cefuroxime, 57% were susceptible to amoxicillin, 14% were susceptible to cefprozil, 9% were susceptible to loracarbef, 2% were susceptible to cefaclor, and 0% were susceptible to azithromycin and clarithromycin. Among S. pneumoniae isolates, 49.6% were penicillin susceptible, 17.9% were intermediate, and 32.5% were penicillin resistant, with penicillin MICs for 50 and 90% of the isolates tested of 0.12 and 4 microg/ml, respectively. Overall, 94% of S. pneumoniae isolates were susceptible to amoxicillin and amoxicillin-clavulanate, 69% were susceptible to azithromycin and clarithromycin, 63% were susceptible to cefprozil and cefuroxime, 52% were susceptible to cefixime, 22% were susceptible to cefaclor, and 11% were susceptible to loracarbef. Although ciprofloxacin has marginal activity against S. pneumoniae, no high-level fluoroquinolone-resistant strains were found. Significant cross-resistance was found between penicillin and macrolides-azalides among S. pneumoniae isolates, with 5% of the penicillin-susceptible strains being macrolide-azalide resistant, compared with 37% of the intermediate isolates and 66% of the resistant isolates. Resistance was highest in S. pneumoniae isolates from patients younger than 10 years of age, middle ear and paranasal sinus specimens, and the southern half of the United States. With the continuing rise in resistance, judicious use of oral antimicrobial agents is necessary in all age groups.

Administration, Oral↗

Susceptibilities of Haemophilus influenzae and Moraxella catarrhalis to ABT-773 compared to their susceptibilities to 11 other agents.

The activity of the ketolide ABT-773 against Haemophilus and Moraxella was compared to those of 11 other agents. Against 210 Haemophilus influenzae strains (39.0% beta-lactamase positive), microbroth dilution tests showed that azithromycin and ABT-773 had the lowest MICs (0.5 to 4.0 and 1.0 to 8.0 microg/ml, respectively), followed by clarithromycin and roxithromycin (4.0 to >32.0 microg/ml). Of the beta-lactams, ceftriaxone had the lowest MICs (</=0.004 to 0.016 microg/ml), followed by cefixime and cefpodoxime (0.008 to 0.125 and </=0.125 to 0.25 microg/ml, respectively), amoxicillin-clavulanate (0.125 to 4.0 microg/ml), and cefuroxime (0. 25 to 8.0 microg/ml). Amoxicillin was only active against beta-lactamase-negative strains, and cefprozil had the highest MICs of all oral cephalosporins tested (0.5 to >32.0 microg/ml). Against 50 Moraxella catarrhalis strains, all of the compounds except amoxicillin and cefprozil were active. Time-kill studies against 10 H. influenzae strains showed that ABT-773, at two times the MIC, was bactericidal against 9 of 10 strains, with 99% killing of all strains at the MIC after 24 h; at 12 h, ABT-773 gave 90% killing of all strains at two times the MIC. At 3 and 6 h, killing by ABT-773 was slower, with 99.9% killing of four strains at two times the MIC after 6 h. Similar results were found for azithromycin, with slightly slower killing by erythromycin, clarithromycin, and roxithromycin, especially at earlier times. beta-Lactams were bactericidal against 8 to 10 strains at two times the MIC after 24 h, with slower killing at earlier time periods. Most compounds gave good killing of five M. catarrhalis strains, with beta-lactams killing more rapidly than other drugs. ABT-773 and azithromycin gave the longest postantibiotic effects (PAEs) of the ketolide-macrolide-azalide group tested (4.4 to >8.0 h), followed by clarithromycin, erythromycin, and roxithromycin. beta-Lactam PAEs were similar and shorter than those of the ketolide-macrolide-azalide group for all strains tested.

Anti-Bacterial Agents↗

Interpretive accuracy of the disk diffusion method for testing newer orally administered cephalosporins against Morganella morganii.

Eight newer orally administered cephems (cefdinir, cefetamet, cefixime, cefpodoxime, cefprozil, ceftibuten, cefuroxime, and loracarbef) were tested against 100 clinical strains of Morganella morganii to determine the extent of serious interpretive very major (false-susceptible) errors when current criteria for the disk diffusion test are applied. Agar dilution MICs and disk diffusion tests were performed as recommended by the National Committee for Clinical Laboratory Standards (Villanova, Pa.) (NCCLS), and the methods were compared by regression analysis using the method of least squares and by error rate bounding. The following results are listed in the order of increasing error rates: cefdinir, loracarbef, and cefprozil, < or = 1% very major error; ceftibuten, 8% minor errors; cefuroxime, 21% minor errors; cefixime, cefpodoxime, and cefetamet, very major errors of 15, 24, and 36%, respectively. M. morganii produces unacceptable rates of test error with cefuroxime, cefixime, cefpodoxime, and cefetamet. The latter two cephalosporins currently have NCCLS table footnote warnings covering the problem observed with this organism. The inclusion of cefuroxime and cefixime in the NCCLS table footnote is strongly recommended.

Administration, Oral↗

Effects of various test media on the activities of 21 antimicrobial agents against Haemophilus influenzae.

As considerable variation in the antimicrobial susceptibility of Haemophilus influenzae has been reported, the effects of various test media on the susceptibility of H. influenzae were studied. MICs were determined by three laboratories for 21 antimicrobial agents against a panel of 100 selected isolates. Testing was performed using a reference NCCLS frozen broth microdilution method with Haemophilus test medium (HTM) broth and dried commercial MIC trays rehydrated with the following media: in-house and commercially prepared HTM broth, Mueller-Hinton broth with 2% lysed horse blood and NAD, IsoSensitest broth with 2% lysed horse blood and NAD, and IsoSensitest broth-based HTM. Overall, all results were very reproducible, with the MIC at which 50% of the isolates tested are inhibited (MIC(50)), MIC(90), and geometric mean MIC being within one doubling dilution by all six methods and at all three testing centers for 15 of the 21 agents tested. Interlaboratory differences were more marked than intralaboratory differences or differences among media. Cefprozil, cefaclor, and trimethoprim-sulfamethoxazole results differed the most, while results for ampicillin, amoxicillin-clavulanic acid, cefdinir, cefixime, ceftriaxone, and clarithromycin were the most reproducible. However, these variations in results caused considerable differences in susceptibility rates for agents for which NCCLS susceptible breakpoints were close to the geometric mean MIC, particularly for cefaclor and cefprozil. This was much less of a problem when pharmacokinetic-pharmacodynamic breakpoints were used. Reproducible susceptibility results were obtained for a wide range of agents against H. influenzae in three laboratories using a variety of media that support the growth of this fastidious species.

Anti-Bacterial Agents↗

Antibacterial properties of investigational, new, and commonly used antibiotics against isolates of Pseudomonas cepacia in Michigan.

Microdilution antimicrobial susceptibility testing was performed with 73 isolates of Pseudomonas cepacia collected from the sputum of patients throughout Michigan with cystic fibrosis. Susceptibility testing was done using new and investigational antibiotics (loracarbef, cefixime, cefpirome, desacetyl-cefotaxime, cefpodoxime, cefmetazole, cefepime, cefprozil, and fleroxacin) and commonly used antibiotics (ceftazidime, mezlocillin, piperacillin, ciprofloxacin, tobramycin, and amikacin). Ceftazidime was the most active antibiotic, and 91.8% of isolates were susceptible to it with MIC50 and MIC90 values of < or = 4 and 16 micrograms/ml, respectively. For mezlocillin, piperacillin, and ciprofloxacin 84.9, 89 and 39.7% of the isolates, respectively, were mostly moderately susceptible. Loracarbef, cefixime, cefprozil, cefmetazole, cefepime, fleroxacin, cefpodoxime, tobramycin, and amikacin did not show activity against P. cepacia. For cefpirome and desacetylcefotaxime 24.7 and 60.3% of the isolates, respectively, were moderately susceptible. Both MIC50 and MIC90 were > 32 micrograms/ml for cefpirome and 32 and > 64 micrograms/ml for desacetylcefotaxime.

Anti-Bacterial Agents↗

Streptococcus pneumoniae resistant to penicillin: incidence and potential therapeutic options.

Streptococcus pneumoniae was recovered from 12 (50%) samples of middle ear fluid of 24 consecutive patients with AOME and in mixed culture of middle ear pathogens from one (4%) additional specimen. Two (15.3%) isolates had intermediate resistance to penicillin (minimal inhibitory concentration (MIC) 0.125 and 1.0 micrograms/mL). The antimicrobial susceptibility to various antimicrobials of 30 S pneumoniae strains recovered from patients seen in the last 12 months was also determined. One of the patients with AOME developed bacteremia that resolved uneventfully, whereas the other developed meningitis. MIC90 was determined from penicillin (2 micrograms/mL), erythromycin (> 32 micrograms/mL), cefaclor (32 micrograms/mL), loracarbef (> or = 64 micrograms/mL), cefixime (16 micrograms/mL), ceftibuten (> 64 micrograms/mL), chloramphenicol (16 micrograms/mL), cefpodoxime (4 micrograms/mL), ciprofloxacin (2 micrograms/mL), cephalexin (> or = micrograms/mL), augmentin (2 micrograms/mL), cefprozil (8 micrograms/mL), clindamycin (64 micrograms/mL), TMP-SXT (> 64 micrograms/mL), clarithromycin (32 micrograms/mL), rifampin (0.06 micrograms/mL), cefuroxime (2 micrograms/mL), cefotaxime (0.25 micrograms/mL), vancomycin (0.25 micrograms/mL), and imipenem (0.5 micrograms/mL). Cefprozil, vancomycin, and rifampin inhibited all strains, whereas cefpodoxime, cefuroxime, clindamycin, and clarithromycin exhibited very good activity.

Anti-Bacterial Agents↗

In vitro activity and pharmacodynamics of oral beta-lactam antibiotics against Streptococcus pneumoniae from southeast Missouri.

STUDY OBJECTIVES: To determine the frequency of reduced susceptibility to penicillin, and to compare the in vitro activity and pharmacodynamics of oral beta-lactam antibiotics against clinical isolates of Streptococcus pneumoniae from southeast Missouri. SETTING: Cape Girardeau, Missouri (population 35,500). Interventions. Minimum inhibitory concentrations (MICs) were determined for penicillin, amoxicillin, amoxicillin-clavulanic acid, cefprozil, cefuroxime, cefpodoxime, cefaclor, and loracarbef by E test for 108 isolates of S. pneumoniae. The MIC50, MIC90, and percentage susceptibility were calculated for each agent. Pharmacokinetic variables were obtained from the literature, and serum concentration-time profiles were simulated for a 25-kg child taking pediatric dosages commonly administered to treat otitis media. The average time above MIC (T > MIC) was calculated as percentage of the dosing interval using free concentrations and the MIC for each individual isolate. Analysis of variance (Scheffe post hoc test) was used to determine differences among agents for in vitro activity and T > MIC (level of significance, p<0.05). MEASUREMENTS AND MAIN RESULTS: The frequency of penicillin-nonsusceptible S. pneumoniae was 28.7% (31/108). For 25 penicillin-intermediate isolates, amoxicillin and amoxicillin-clavulanic acid were significantly more active than cefprozil, cefaclor, and loracarbef. The T > MIC for amoxicillin and amoxicillin-clavulanic acid, simulated at 13.3 mg/kg every 8 hours, was significantly longer than that for all other beta-lactams. CONCLUSION: Amoxicillin and amoxicillin-clavulanic acid have superior in vitro activity and longer T > MIC for penicillin-intermediate isolates than the other oral beta-lactams.

Administration, Oral↗

[In vitro activity of fluoroquinolones and oral beta lactam antibiotics against clinical isolates of Escherichia coli].

We studied the in vitro activity of amoxicillin-clavulanic acid, cefprozil, cefuroxime, cefpodoxime, ceftibuten, cefixime, ciprofloxacin and sparfloxacin against 400 strains of Escherichia coli. The strains were obtained from urine cultures from patients with community acquired urinary tract infection who were treated in our hospital in 1997 and 1998. Among the six betalactams, ceftibuten and cefixime were the most active in vitro with MIC90 of 0.5 mg/l. Both antimicrobials were 2- and 16-fold more active than cefpodoxime (MIC90 1 mg/l) and cefprozil (MIC90 8 mg/l), respectively. However, overall, the four cephalosporins inhibited between 95% and 99% of isolates. Cefuroxime and amoxicillin-clavulanic acid showed less activity with a MIC90 of 16 mg/l. The percentage of fluoroquinolone-resistant strains was 24% with a similar activity to ciprofloxacin (MIC90 32 mg/l) and sparfloxacin (MIC90 64 mg/l).

Administration, Oral↗

A critical review of the new oral cephalosporins. Considerations and place in therapy.

Oral cephalosporins are key antimicrobials in the family physician's therapeutic armamentarium. The list of available agents within this class has been recently expanded to include cefixime, cefprozil, cefpodoxime proxetil, and loracarbef. Each of these antibiotics has differing antimicrobial coverage patterns and approved therapeutic uses. Compared with older, more established antimicrobials such as penicillin, amoxicillin, cefaclor, a combination of amoxicillin and clavulanate potassium, and erythromycin, the newer cephalosporins offer little, if any, therapeutic advantage. Clinical efficacy has been shown to be equal in virtually all studies comparing the newer cephalosporins with traditional agents for various community-acquired infections. While the four newer agents may be given less often, they are relatively expensive. In light of the available clinical data, the newer oral cephalosporins should be reserved as second- or third-line choices.

Administration, Oral↗

Validation of Etest for seven antimicrobial agents using regulatory criteria for the assessment of antimicrobial susceptibility devices.

Etest, a stable-gradient antimicrobial susceptibility test method (AB Biodisk, Solna, Sweden), was compared to the agar dilution method for tests with amikacin, tobramycin, aztreonam, cefdinir, cefprozil, ceftazidime and sparfloxacin. The study design followed recommended guidelines for 510(k) application by the U.S. Food and Drug Administration (FDA). Results demonstrated Etest accuracy (MIC +/- 1.0 log2 dilutions compared to agar dilution MIC) to be 90.4% with only one of 1150 comparisons showing a reproducible variation of 2 log2 dilutions. Categorical equivalency was > or = 92% for all drugs except ceftazidime (82 to 89%), but false-susceptible error was rare (< 0.1%). Etest was very reproducible (100% of results +/- 1.0 log2 dilution) and quality control results conformed to published MIC ranges. The Etest seems to render accurate results for these seven antimicrobial agents evaluated.

Amikacin↗