We studied the efficacy of antimicrobial agents against Staphylococcus aureus (S. aureus) and Streptococcus pyogenes (S. pyogenes) isolated from skin infections in 1992. For S. aureus, we measured the minimum inhibitory concentrations (MICs) of the following 10 drugs: methicillin (DMPPC), cefaclor (CCL), gentamicin (GM), erythromycin (EM), clindamycin (CLDM), minocycline (MINO), vancomycin (VAN), fusidic acid (FA), ofloxacin (OFLX) and nadifloxacin (NDFX); for S. pyogenes, we determined the MICs of the following 9 drugs: ampicillin (ABPC), amoxicillin (AMPC), cefpodoxime proxetil (CPDX-PR), erythromycin (EM), clindamycin (CLDM), minocycline (MINO), norfloxacin (NFLX), of loxacin (OFLX) and nadifloxacin (NDFX). These drugs are frequently used to treat skin infections, either systemically or topically. NDFX is a new synthetic fluoroquinolone, recently developed for use as a topical acne medication in Japan. It is used NDFX for acne, but not for skin infections. There were no strains of S. aureus resistant to NDFX, VAN or FA. The resistance (> or = 12.5 micrograms/ml) of S. aureus was highest to GM and lowest to OFLX. Four strains of methicillin-resistant (> or = 12.5 micrograms/ml) S. aureus (MRSA) were found. In contrast, no resistant strains of S. pyogenes were found except to MINO. Only two strains of S. pyogenes were susceptible to MINO. The sensitivity of S. pyogenes to ABPC, AMPC, CPDX-PR, EM and CLDM was very good. All the strains were susceptible at a MIC below > or = 0.05 microgram/ml. However, the S. pyogenes strains were not very sensitive to the new quinolones, especially NFLX. We concluded that penicillins, cephalosporins and macrolides are still effective against streptococcal infections.(ABSTRACT TRUNCATED AT 250 WORDS)
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The bioavailability of cefpodoxime proxetil tablets relative to an oral solution of cefpodoxime proxetil in a sucrose/alcohol/citric acid vehicle was studied in 11 healthy volunteers in a randomized, crossover study. Fasted subjects took one cefpodoxime proxetil 100 mg tablet or 50 mL of a 2 mg mL-1 cefpodoxime proxetil oral solution on two separate occasions. In a third study period, all subjects took a 100 mg dose of the oral solution with a high-fat meal to investigate the effect of food on cefpodoxime proxetil absorption from the oral solution. Serial blood samples were obtained over a 24 h period, and urine was collected for 48 h after dosing. Cefpodoxime concentrations in plasma and in urine were determined using HPLC methods. The bioavailability of cefpodoxime proxetil tablets relative to the oral solution was 82%, as determined from AUC ratios. There was no difference in the rate of cefpodoxime absorption between dosage forms. Food had no effect on the extent of drug absorption from the oral solution but did result in delayed absorption. These results suggest that complete dissolution of cefpodoxime proxetil is critical for optimal bioavailability.
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Cefpodoxime proxetil, a new oral cephalosporin, is the prodrug ester of cefpodoxime. Minimal inhibitory concentrations (MIC) of RU 51746 (sodium salt of cefpodoxime: CPD) were evaluated by agar dilution for 1 696 bacterial strains isolated in 5 hospitals. For Enterobacteriaceae, MIC 50 and 90% were respectively (micrograms/ml): (1) naturally non bêtalactamase producing species: E. coli, Shigella and Salmonella 0.25-0.5; P. mirabilis 0.06-0.12. (II) chromosomal penicillinase producing species: Klebsiella 0.12-1. (III) chromosomal cephalosporinase producing species: E. cloacae and C. freundii 2-greater than 128; S. marcescens 2-64; indole + Proteus 0.25-64; P. stuartii 0.25-16. Activity of CPD was not modified on plasmid mediated penicillinase producing strains, but CPD was inactive on cephalosporinase hyperproducing strains, and on broad spectrum bêtalactamases producing strains. CPD was inactive on P. aeruginosa (MIC greater than or equal to 64) and on A. baumannii (16-pi 128). Haemophilus, regardless on bêtalactamase production status, were very susceptible to CPD (MIC less than or equal to 0.25) and B. catarrhalis was generally inhibited by 0.12 to 1. CPD was poorly active on methicillin susceptible Staphylococci (MIC 50 and 90%: 2-4) and inactive on methicillin resistant strains. Enterococci and Listeria monocytogenes were generally resistant; Streptococci A, B, C, G and Pneumococci were inhibited by low concentration: 0.002 to 0.25 (MIC 50 and 90%: 0.016-0.032) whereas MIC for other Streptococci were 0.004 to 32 (MIC 50 and 90%: 0.25-4). These antibacterial properties placed CPD in excellent position among oral cephalosporins.
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Cefpodoxime proxetil (RU 51 807) is the oral prodrug of cefpodoxime (RU 51 763), a third generation cephalosporin. The antibacterial activity of cefpodoxime was compared with the activities of amoxicillin in combination with clavulanic acid (AUG), cefaclor (CCl), cefuroxime (CXM) and cefotaxime (CTX), against species of Enterobacteriaceae showing a resistance pattern against ampicillin (AMP), ticarcillin (TIC), cefalothin (CFT) and cefotaxime (CTX) respectively. For strains AMP and TIC R, CFT and CTX S, MICs 90% of cefpodoxime were 1 mg/l (E. coli), 0.5 (K. pneumoniae), 0.06 (P. mirabilis), 0.5 (Shigella sp.) and 1 (Salmonella sp.); they were 4 to 16 times as high for AUG -CCL -CXM and 4 to 16 times as low for CTX. For K. pneumoniae AMP and TIC R, CFT I/R and CTX S, similar résults were obsereved for the 5 beta-lactam antibiotics, but with an activity 10 times as low. Among the species AMP R, TIC S, CFT R and CTX S, cefpodoxime was active against P. rettgeri, P. stuartii, C. diversus, E. aerogenes and Y. enterocolitica (MICs 90% ranging from 2 to 4 mg/l; from 0.12 to 1 mg/l for CTX) and less active or inactive against P. vulgaris, E. cloacae, S. marcescens, M. morganii and E. coli (MICs 90% ranged from 16 to 32 mg/l; from 1 to 4 mg/l for CTX).(ABSTRACT TRUNCATED AT 250 WORDS)
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The Rf values for CEFPO, AMBRO, and paracetamol were found to be 0.69 ± 0.005, 0.49 ± 0.0057, and 0.31 ± 0.0054, respectively. The stability of CEFPO and AMBRO in plasma was confirmed during three freeze-thaw cycles (-20°C), on bench during 24 h and post preparative during 48 h.
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A number of oral third-generation cephalosporins (cefixime, cefetamet pivoxil, ceftibuten and cefpodoxime proxetil) have been widely trialled and are becoming available. In addition, cefdinir may also be marketed. Compared with first- and second-generation agents, the oral third-generation cephalosporins have an improved antibacterial spectrum and reduced minimum inhibitory concentrations against common Gram-negative pathogens. In contrast, with the exception of cefdinir, they are less active against Staphylococcus aureus. They have favourable pharmacokinetic profiles and are generally administered in once- or twice-daily regimens. They are well tolerated, but cefixime has been associated with a particularly high rate of diarrhoea. Possible clinical indications for the use of oral third-generation cephalosporins include upper and lower respiratory, genitourinary and soft-tissue infections and follow-on treatment of severe infections requiring hospitalisation. At present, these drugs offer no particular clinical advantages over standard therapy in most circumstances. However, they may be considered where there is hypersensitivity to penicillins, a high incidence of resistance to first-line therapy in the community, or failure of standard therapy. Further studies are needed to define the efficacy of oral third-generation agents in the prevention of rheumatic fever and as follow-on therapy for severe infections. The oral third-generation cephalosporins are generally more expensive than standard agents, but detailed studies that include extended costs (e.g. treatment of adverse effects, treatment of clinical failure, return visits to physicians) have yet to be reported.
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Mean plasma protein binding for cefpodoxime and cephalexin was 82.6% and 20.8%, respectively. Mean ± SD values for cephalexin in plasma were determined for peak plasma concentration (Cmax, 31.5±11.5 μg/mL), area under the time-concentration curve (AUC, 155.6±29.5 μg•h/mL), and terminal half-life (T½, 4.7±1.2 hours); corresponding values in ISF were 16.3±5.8 μg/mL, 878±21.0 μg•h/mL, and 3.2±0.6 hours, respectively. Mean±SD values for cefpodoxime in plasma were 33.0±6.9 μg/mL (Cmax), 282.8±44.0 μg•h/mL (AUC), and 5.7±0.9 hours (T1/2); corresponding values in ISF were 4.3±2.0 μg/mL, 575±174 μg•h/mL, and 10.4±3.3 hours, respectively.
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To assess the efficacy and safety of a single-dose therapy for acute uncomplicated cystitis (AUC), we compared 4 treatment regimens in 120 women. Patients eligible for the study were randomly assigned to one of four treatment groups: Ciprofloxacin (CPFX) 200 mg in a single oral dose (group A); 200 mg once daily for 3 days (group B); 200 mg twice daily for 3 day (group C); and cefpodoxime-proxcetil (CPDX-PR) 200 mg once daily for 3 days (group D). The efficacy was evaluated 3 days after the single-dose therapy or at the end of a three-day therapy according to the criteria proposed by the Japanese UTI Committee. The overall clinical efficacy in a total of 107 patients was evaluated to be excellent, moderate, and poor in 72 (67.3%), 35 (31.8%), and 1 (0.9%), respectively. The causative organisms were eradicated in 88.0, 85.2, 85.2, and 82.1% of the patients in groups A, B, C, and D, respectively. Recurrence was identified in 3 (2 in group A and one in group D) of 16 patients who were followed at 2 to 3 weeks after the treatment. No adverse reactions related to the antibiotics were recognized in the study. There were no significant differences in the clinical efficacy or recurrence rate among these four treatment regimens. These results indicate that the single-dose therapy of CPFX is the treatment of choice in women with AUC.