Search

Background: The objectives of this study were; (I) to determine the proportion of pathogens isolated from patients with infected chronic wounds in the surgical ward of MRRH that are resistant to the third-generation cephalosporins and (II) to determine the factors associated with resistance to third-generation cephalosporins in the surgical ward of MRRH., Method(s): This study was a descriptive analytical survey of bacterial isolates from infected chronic wounds among patients admitted in the surgical ward of MRRH, Uganda. Seventy five (75) study participants were recruited in the study using convenient sampling technique. Bacterial culture and identification was performed using standard microbiology laboratory procedures whereas broth microdilution method was used to establish the susceptibility of the identified pathogens. Data for objective one (1) was summarized as proportions while the categorized variables were analyzed using logistic regression to determine whether they were associated with the resistance patterns. The level of significance was preset at 5% and p-values less than 0.05 were considered statistically significant., Results: Generally, all isolates had complete susceptibility (100%) to Cefoperazone+Sulbactam 2g except 7.1% of proteus spp that were resistant. Of all the bacterial isolates studied, Staphylococcus aureus, Enterobacter agglomerans, providencia spp and pseudomonas earuginosa had complete resistance (100%) to Cefopodoxime 200mg while providencia spp and pseudomomas earuginosa had complete resistance (100%) to Cefixime 400mg and cefotaxime 1g. Finally, higher odds of bacterial resistance to more 2 brands of the third generation cephalosporins were observed among participants who had prior exposure to the third generation cephalosporins (OR, 2.22, 95% CI, 0.80-6.14), comorbidities (OR, 1.76, 95% CI, 0.62-4.96) and those who had more than two hospitalizations in a year (OR, 1.39, 95% CI 0.46-4.25). However, multivariate logistic regression was not performed since no factor was significantly associated with resistance to more than two brands of third generation cephalosporins (p >0.05)., Conclusion: This study found that cefixime and cefpodoixme had high rates of resistance and should not be used in routine management of infected chronic wounds. In addition, the factors investigated in this study were not significantly associated with bacterial resistance to more than two brands of third generation cephalosporins., Competing Interests: The authors have declared that no competing interests exist.

To enable future comparison of the antimicrobial susceptibility data between bacteria obtained from animals and humans, it is necessary to compare the relationships between minimum inhibitory concentrations (MICs) of veterinary and human medicine. We evaluated the relationship between the MIC of ceftiofur (CTF) and the MICs of other third-generation cephalosporins (TGCs): cefotaxime (CTX), cefpodoxime (CPDX), and ceftazidime (CAZ), determined by the broth microdilution method using 118 cefazolin-resistant Escherichia coli isolates from food-producing animals. Using the Clinical and Laboratory Standards Institute criteria, very major classification errors were observed only in CAZ (17.8%, 21 of 118); major and minor errors were observed in all TGCs (CTX: 0.8% [1 of 118] and 9.3% [11 of 118]; CPDX: 9.3% [11 of 118] and 6.8% [8 of 118]; CAZ: 2.5% [3 of 118] and 9.3% [11 of 118], respectively). The Spearman correlation coefficients between the MICs of CTF and CTX, CPDX, and CAZ were 0.765, 0.731, and 0.306, respectively. The sensitivity and specificity values were 100.0% and 81.8% for CTX, 99.0% and 27.3% for CPDX, and 76.0% and 86.4% for CAZ compared with CTF. The C-statistic was 0.978 for CTF and CTX, 0.953 for CPDX, and 0.798 for CAZ. For the TGCs evaluated in our study, testing for CTX susceptibility results showed the highest correlation with the results given when testing for CTF susceptibility.

Rapid detection and reporting of third generation cephalosporine resistance (3GC-R) and of extended spectrum betalactamases in Enterobacteriaceae (ESBL-E) is a diagnostic and therapeutic priority to avoid inefficacy of the initial antibiotic regimen. In this study we evaluated a commercially available chromogenic screen for 3GC-R as a predictive and/or confirmatory test for ESBL and AmpC activity in clinical and veterinary Enterobacteriaceae isolates. The test was highly reliable in the prediction of cefotaxime and cefpodoxime resistance, but there was no correlation with ceftazidime and piperacillin/tazobactam minimal inhibitory concentrations. All human and porcine ESBL-E tested were detected with exception of one genetically positive but phenotypically negative isolate. By contrast, AmpC detection rates lay below 30%. Notably, exclusion of piperacillin/tazobactam resistant, 3GC susceptible K1+ Klebsiella isolates increased the sensitivity and specificity of the test for ESBL detection. Our data further imply that in regions with low prevalence of AmpC and K1 positive E. coli strains chromogenic testing for 3GC-R can substitute for more time consuming ESBL confirmative testing in E. coli isolates tested positive by Phoenix or VITEK2 ESBL screen. We, therefore, suggest a diagnostic algorithm that distinguishes 3GC-R screening from primary culture and species-dependent confirmatory ESBL testing by βLACTATM and discuss the implications of MIC distribution results on the choice of antibiotic regimen.

The process of degradation was studied by using an HPLC-DAD method. Two degradation products were identified with a hybrid ESI-Q-TOF mass spectrometer. The influence of temperature and relative air humidity (RH) on the stability of cefoselis sulfate was investigated. In the solid state at increased RH the degradation of cefoselis sulfate was an autocatalytic reaction of the first order with respect to substrate concentration while in dry air was first-order reaction depending on the substrate concentration. The kinetic and thermodynamic parameters of degradation were calculated., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Ceftiofur is a highly effective veterinary cephalosporin, yet it is rapidly degraded by bacteria in the gut. The goal of this work was to directly determine the mechanism of ceftiofur degradation by the bovine intestinal isolate Bacillus cereus P41. B. cereus P41 was isolated from the feces of a cow that had not been treated with cephalosporins, and was found to rapidly degrade ceftiofur in culture. Analysis of spent culture media by HPLC/UV and HPLC/MS revealed one major metabolite of ceftiofur, with a negative ion m/z of 127. Comparison of ceftiofur, ceftriaxone, and cefpodoxime degradation suggested that the major stable ceftiofur metabolite was the thiofuroic acid group eliminated from the C-3 position of the drug after hydrolysis by β-lactamase. Genomic DNA from B. cereus P41 was cloned into Escherichia coli, and the transformants were screened for growth in the presence of ceftiofur. DNA sequencing of the plasmid pHSG299-BC-3 insert revealed the presence of a gene encoding a metallo-β-lactamase. Incubation of ceftiofur with either the E. coli transformant or a commercial B. cereus metallo-β-lactamase showed degradation of the drug and formation of the same major metabolite produced by B. cereus P41. These data demonstrate that a metallo-β-lactamase plays a major role in the degradation of ceftiofur by the bovine intestinal bacterium B. cereus P41., (Published by Elsevier B.V.)

The use of extended-spectrum cephalosporins in food animals has been suggested to increase the risk of spread of Enterobacteriaceae carrying extended-spectrum β-lactamases to humans. However, evidence that selection of extended-spectrum cephalosporin-resistant bacteria owing to the actual veterinary use of these drugs according to criteria established in cattle has not been demonstrated. In this study, we investigated the natural occurrence of cephalosporin-resistant Escherichia coli in dairy cattle following clinical application of ceftiofur. E. coli isolates were obtained from rectal samples of treated and untreated cattle (n = 20/group) cultured on deoxycholate-hydrogen sulfide-lactose agar in the presence or absence of ceftiofur. Eleven cefazoline-resistant isolates were obtained from two of the ceftiofur-treated cattle; no cefazoline-resistant isolates were found in untreated cattle. The cefazoline-resistant isolates had mutations in the chromosomal ampC promoter region and remained susceptible to ceftiofur. Eighteen extended-spectrum cephalosporin-resistant isolates from two ceftiofur-treated cows were obtained on ceftiofur-supplemented agar; no extended-spectrum cephalosporin-resistant isolates were obtained from untreated cattle. These extended-spectrum cephalosporin-resistant isolates possessed plasmid-mediated β-lactamase genes, including bla(CTX-M-2) (9 isolates), bla(CTX-M-14) (8 isolates), or bla(CMY-2) (1 isolate); isolates possessing bla(CTX-M-2) and bla(CTX-M-14) were clonally related. These genes were located on self-transmissible plasmids. Our results suggest that appropriate veterinary use of ceftiofur did not trigger growth extended-spectrum cephalosporin-resistant E. coli in the bovine rectal flora; however, ceftiofur selection in vitro suggested that additional ceftiofur exposure enhanced selection for specific extended-spectrum cephalosporin-resistant β-lactamase-expressing E. coli clones.

Aim: This study aims to evaluate the clinical efficacy and safety of intravenous Cefoselis injection for the treatment of acute moderate and severe bacterial infections., Patients and Methods: A multicenter, double-blind, randomized clinical trial was carried out using Cefepime as control. Patients received 1.0 g of either Cefoselis or Cefepime for moderate infections or 2.0 g for severe infections at an interval of 12 hours for 7 to 14 days. A total of 276 patients (138 with Cefoselis, 138 with Cefepime) with respiratory or urinary tract infections were enrolled in the study. Up to 137 and 124 patients receiving Cefoselis and 132 and 125 patients receiving Cefepime were eligible for the ITT (intent to treat) and PP (per protocol) analyses, respectively., Results: At the end of the treatment, the cure rates and effective rates were 59.68% (74/124) and 93.55% (116/124) with Cefoselis, and 56.00% (74/124) and 90.40% (116/124) with Cefepime. The bacterial eradication rates of the two groups were 90.32% and 93.85%, respectively. No statistical differences were observed on the above-mentioned parameters between the two groups (all p > 0.05). Adverse events, mainly mild aminotransferase elevation and mild leukopenia, were observed in 11.59% (16/138) and 13.77% (19/138) of patients with Cefoselis and Cefepime, respectively (p > 0.05)., Conclusions: Cefoselis is an effective and safe choice against acute moderate and severe respiratory infections and UTI (urinary tract infection).

Purpose: To evaluate resistances mediated by extended-spectrum β-lactamases (ESBLs) and AmpC β-lactamases among Gram-negative bacteria recovered from ocular infections., Methods: As per the Clinical Laboratory Standards Institute M100-S-16 document, a total of 135 Gram-negative bacilli were recovered from ocular specimens and were subjected to phenotypic confirmation for ESBL production by the double-disc synergy test, cephalosporin and clavulanate combination disc test and E test, and, for AmpC β-lactamase, the modified double-disc approximation method and AmpC disc test., Results: In the double-disc synergy test, 21 (15.5%) isolates showed positive results against the cefpodoxime disc, 19 (14%) against cefpodoxime and cefotaxime, 15 (11%) against cefpodoxime, cefotaxime and ceftriaxone and 10 (7%) isolates were against cefpodoxime, cefotaxime, ceftriaxone and ceftazidime discs. In the cephalosporin/clavulanate combination disc test, 19 (14%) isolates showed positive results against cefotaxime with clavulanic acid and 10 (7%) isolates against ceftazidime with clavulanic acid. In the E test, 10 (7%) isolates displayed positive results against ceftazidime and 19 (14%) against cefotaxime. In the AmpC disc test for phenotypic confirmation, indentations were observed in 15 (11%) isolates with flattening also occurring in 10 (7%) isolates., Conclusion: The incidences of ESBL- and AmpC β-lactamase-mediated resistances are found to be 7 and 18.5% among ocular isolates, respectively, and are more prevalent among the strains of Escherichia coli and Klebsiella pneumoniae., (Copyright © 2011 S. Karger AG, Basel.)

Antimicrobial resistance (AMR) in Neisseria gonorrhoeae remains a global public health problem. Susceptibility to first-line treatment extended-spectrum cephalosporins (ESCs) is decreasing worldwide resulting in therapeutic failures with oral ESCs. This study describes a cefpodoxime 10 μg disc test for screening for gonococci containing a penA mosaic allele encoding a mosaic penicillin-binding protein 2 (PBP2) and decreased ESC susceptibility. Selected clinical gonococcal isolates (n = 315), containing a high proportion of gonococci with decreased ESC susceptibility and high geographical, temporal and genetic diversity, were examined using agar dilution (n = 149; cefpodoxime and ceftriaxone) and Etest (n = 315; cefixime), and disc diffusion using a commercially available cefpodoxime 10 μg disc (n = 315). penA sequencing was performed on all isolates. The 2008 WHO gonococcal reference strains (n = 8) were included as quality controls. Using a ≤11 mm annular radius of growth inhibition as the breakpoint for the cefpodoxime 10 μg disc, all 78, with exception of one isolate (13 mm), mosaic PBP2-containing isolates, which also displayed decreased susceptibility to oral ESCs, were identified. In addition, 85 non-mosaic PBP2-containing isolates (44% of which contained a PBP2 A501 alteration) had annular radii ≤11 mm and raised minimal inhibitory concentrations to the ESCs. Screening for detection of mosaic PBP2-containing gonococci and decreased ESC susceptibility, most pronounced to oral ESCs, using a commercially available cefpodoxime 10 μg disc was rapid, inexpensive and sensitive. This test can be used in AMR surveillance programmes for public health purposes especially in less-resourced settings. Further studies to refine this disc testing-based approach are in progress., (© 2011 The Authors. APMIS © 2011 APMIS.)

Objectives: Aminopenicillin-induced exanthema poses a problem in the management of infectious diseases. Due to theoretically possible immunological cross-reactivity, all beta-lactam drugs, i.e. penicillins, penicillin derivatives and cephalosporins, are usually avoided. The available alternative antibiotics (macrolides, quinolones and glycopeptides) may be less effective, have more side effects, and their use increases medical costs. Moreover, their use contributes to the increasing bacterial resistance to antibiotics. The aim of the study is to demonstrate that patients with aminopenicillin-induced exanthema may receive specific beta-lactams for future antibiotic therapy., Methods: Skin testing followed by oral challenges to identify beta-lactams that are tolerated by patients despite confirmed delayed-type non-immunoglobulin E (IgE)-mediated allergic hypersensitivity to aminopenicillins., Results: Sixty-nine out of 71 patients (97.2%) with non-IgE-mediated allergic hypersensitivity to aminopenicillins tolerate cephalosporins without an aminobenzyl side chain such as cefpodoxime or cefixime and 51 patients (71.8%) also tolerate phenoxymethyl penicillin., Conclusions: The majority of patients with non-IgE-mediated allergic hypersensitivity to aminopenicillins do not cross-react to certain cephalosporins or phenoxymethyl penicillin. Skin and drug challenge tests can be helpful to determine individual cross-reactivity.

Pharmacodynamic parameters and bactericidal activity against Streptococcus pneumoniae were investigated by simulating total and free serum concentrations of cefpodoxime versus cefditoren. Total drug T>MIC against the penicillin-intermediate (PISP) and resistant (PRSP) strains were 70.6% and 42.9% for cefpodoxime, and 89.6% and 62.5% for cefditoren, respectively. Comparing activity of free versus total cefpodoxime, there were reductions of 8.5% and 19.1% in T>MIC, related to bactericidal activity reductions from approximately 4.5 to 3 log(10), and from 3 to 2.5 log(10 )against PISP and PRSP, respectively, at 10-12h. For cefditoren, reductions of 45.4% and 100% in T>MIC, were related to bactericidal activity reductions from approximately 5.5 to 2-2.5 log(10 )and from approximately 2.5 to 1.5 log(10 )against PISP and PRSP, respectively, at 10-12h. Higher differences in activity were found against the less resistant strains when comparing total versus free-drug profile.

In 2001, fluoroquinolone-resistant Escherichia coli isolates emerged in Japan in patients with uncomplicated urinary tract infection (UTI), and accounted for ca. 8% of isolates. This is a worldwide occurrence as reported by the ECO.SENS study. The number of fluoroquinolone- and cephem-resistant Enterobacteriaceae isolates from patients with complicated UTI is increasing. Most cephem-resistant isolates of E. coli, Klebsiella pneumoniae and Proteus mirabilis produce extended-spectrum beta-lactamases (ESBLs). The rates of ESBL-producing Enterobacteriaceae differ between countries but there are ESBL producers in urinary Enterobacteriaceae isolates in most countries. More seriously, most nosocomial ESBL producers are also resistant to non-beta-lactams, such as the fluoroquinolones, fosfomycin and co-trimoxazole. This causes serious problems in the chemotherapy of cystitis.

Ceftobiprole, a broad-spectrum pyrrolidinone-3-ylidenemethyl cephem currently in phase III clinical trials, had MICs between 0.008 microg/ml and 8.0 microg/ml for 321 clinical isolates of Haemophilus influenzae and between < or =0.004 microg/ml and 1.0 microg/ml for 49 clinical isolates of Moraxella catarrhalis. Ceftobiprole MIC(50) and MIC(90) values for H. influenzae were 0.06 microg/ml and 0.25 microg/ml for beta-lactamase-positive strains (n = 262), 0.03 microg/ml and 0.25 microg/ml for beta-lactamase-negative strains (n = 40), and 0.5 microg/ml and 2.0 microg/ml for beta-lactamase-negative ampicillin-resistant strains (n = 19), respectively. Ceftobiprole MIC(50) and MIC(90) values for beta-lactamase-positive M. catarrhalis strains (n = 40) were 0.12 microg/ml and 0.5 microg/ml, respectively, whereas the ceftobiprole MIC range for beta-lactamase-negative M. catarrhalis strains (n = 9) was < or =0.004 to 0.03 microg/ml. Ceftriaxone MICs usually were generally at least twofold lower than those of ceftobiprole, whereas amoxicillin-clavulanate MICs usually were higher than those of ceftobiprole. Azithromycin and telithromycin had unimodal MIC distributions against H. influenzae, with MIC(90) values of azithromycin and telithromycin of 2 microg/ml and 4 microg/ml, respectively. Except for selected quinolone-nonsusceptible H. influenzae strains, moxifloxacin proved highly active, with MIC(90) values of 0.12 microg/ml. Time-kill analyses showed that ceftobiprole, ceftriaxone, cefpodoxime, amoxicillin-clavulanate, azithromycin, telithromycin, and moxifloxacin were bactericidal at 2x MIC by 24 h against all 10 H. influenzae strains surveyed. Only modest increases in MICs were found for H. influenzae or M. catarrhalis clones after 50 serial passages in the presence of subinhibitory concentrations of ceftobiprole, and single-passage selection showed that the selection frequency of H. influenzae or M. catarrhalis clones with elevated ceftobiprole MICs is quite low.

Objective: To compare the pharmacokinetics/pharmacodynamics property of cefdinir, cefpodoxime proxetil and cefaclor against common bacteria of community acquired infections and evaluate the recommended regimens., Methods: The antibacterial activities of 3 agents against 238 clinical isolates were determined by standard agar dilution test and the pharmacokinetics of these antibiotics in male healthy volunteers were conducted in Latin-square manner. The time over MIC (T > MIC) of serum antibiotic concentrations were calculated with pharmacokinetic equation and MIC., Results: The value of MIC90 s cefdinir against these bacterial strains except penicillin non-sensitive pneumococci were 0.031-1 mg/L. Cefpodoxime held similar antibacterial activity with cefdinir, but was less potent against staphylococci. Cefaclor had much higher MIC values than other two drugs. After oral administration of 250 mg cefaclor, the drug concentration quickly reached peak concentration of 4.95 mg/L +/- 2.41 mg/L and the eliminative half time was 0.69 h +/- 0.6 h; the Tmax, Cmax and T1/2beta of cefdinir and cefpodoxime after oral administration of 100 mg were 2.5 h +/- 0.48 h, 0.81 mg/L +/- 0.19 mg/L, 1.73 h +/- 0.3 h and 2.38 h +/- 0.43 h, 1.12 mg/L +/- 0.28 mg/L, 1.92 h +/- 0.55 h, respectively. T > MIC of cefdinir in thrice daily administration were longer than 40% of medication interval against most of the tested isolates; no T > MIC period was found in cefpodoxime against staphylococci and the T > MICs of cefaclor after 250 mg oral administration were shorter than expected values against most bacteria., Conclusion: With powerful antibacterial activity, the T > MICs of cefdinir after 100 mg oral administration can meet with the clinical requirement in most infections; PK/PD value of cefpodoxime proxetil against staphylococci is lower than expectancy and 250 mg cefaclor 3 times daily is not enough to the treatment of common community acquired infections, the regimens of cefpodoxime proxetil and cefclor should be furtherly optimized.

Background: Recurrent acute pharyngotonsillitis remains a common illness in children and young adults and can lead to serious complications if not treated. cefpodoxime proxetil is a second-generation oral cephalosporin, which shows potent antibacterial activity against both Gram-positive and Gram-negative bacteria and high stability in the presence of beta-lactamases., Objective: We aimed to evaluate the efficacy of second-generation cephalosporins in the prophylaxis of recurrent pharyngotonsillitis in children., Methods: A total of 180 children aged between 4 and 14 years with recurrent pharyngotonsillitis were randomized to receive either cefpodoxime proxetil (100 mg twice a day, 6 days a month for 6 months) or placebo (at the same dosage)., Results and Conclusions: Our results show that treatment with cefpodoxime proxetil may be effective in reducing symptoms of recurrent pharyngotonsillitis and preventing recurrences without causing side effects or developing bacterial resistance.

As the post-marketing surveillance of cefpodoxime proxetil (Banan), MICs of cefpodoxime (CPDX, an active form of Banan) against 1090 clinical isolates of 22 species from 15 medical institutions all over Japan from June 2000 to March 2001 were measured using the broth microdilution method approved by the Japanese Society of Chemotherapy and compared with those of oral cephem antibacterials, cefaclor, cefdinir, cefditoren, and cefcapene. In this study, remarkable change in the activity of CPDX was observed in Streptococcus pneumoniae and Haemophilus influenzae compared with the susceptibility in the studies before Banan was launched. This cause is considered to be the increase in the incidence of the following resistant strains: penicillin-intermediate S. pneumoniae (47.3%), penicillin-resistant S. pneumoniae (PRSP, 15.1%), and beta-lactamase-negative ampicillin-resistant (BLNAR) H. influenzae (24.0%), which were scarcely isolated in 1989 when Banan was launched. Other tested drugs also exhibited low activity against these resistant strains. However, CPDX showed comparatively good activity with MIC90 of 2 micrograms/mL against PRSP. Against methicillin-susceptible Staphylococcus spp., Streptococcus pyogenes, Streptococcus agalactiae, and Moraxella catarrhalis, CPDX also showed comparatively good activity with MIC90 of < or = 4 micrograms/mL, which was almost equal to that in the studies before its marketing. Against quinolones-resistant Neisseria gonorrhoeae, CPDX showed excellent activity with MIC90 of 0.5 microgram/mL. Against members of the family Enterobacteriaceae except for Citrobacter freundii, Enterobacter spp., Proteus vulgaris, and Morganella morganii, CPDX showed good activity. However, in Escherichia coli, Klebsiella spp. Proteus spp., and Providencia spp., there are some high-resistant strains to all tested drugs including CPDX. Against Peptostreptococcus spp., MIC90 of CPDX was 8 micrograms/mL and its MIC range was widely distributed from 0.03 to 32 micrograms/mL, which were similar to those in the studies before its marketing. In this study, CPDX showed the decrease in the activity against several species as did other drugs tested, but against most of species tested, CPDX maintained good activity. Furthermore, it is necessary to pay much attention to the trend of resistant strains.

Background: According to recently issued treatment guidelines, appropriate empiric choices for ambulatory patients with community-acquired pneumonia (CAP) are a macrolide, doxycycline (for patients aged > or = 8 years), or an oral beta-lactam agent with good activity against pneumococci., Objective: This study was designed to compare cefditoren pivoxil, a new beta-lactam, with cefpodoxime proxetil, a beta-lactam with an established role in the treatment of CAP., Methods: This was a multicenter, prospective, randomized, double-blind study conducted in the United States and South Africa. Ambulatory patients with a diagnosis of CAP were randomized to 14 days of treatment with cefditoren 200 or 400 mg BID or cefpodoxime 200 mg BID. Assessments of clinical cure and pathogen eradication were conducted at 2 visits during treatment, 1 posttreatment visit (s48 hours after completion of treatment), and 1 follow-up visit (7-14 days after completion of treatment). The development of resistant pathogens was assessed at the follow-up visit but not thereafter. The relative cost of treatment was not assessed., Results: The study enrolled 851 patients. Comparable clinical cure rates were observed among evaluable patients in the 3 treatment groups at both the posttreatment and followup visits: at the posttreatment visit, cure rates were 90.5% (162/179) for cefditoren 200 mg, 89.7% (148/165) for cefditoren 400 mg, and 92.2% (153/166) for cefpodoxime 200 mg; at the follow-up visit, they were a respective 88.4% (160/181), 87.2% (143/164), and 90.4% (151/167). Of the 171 strains of Streptococcus pneumoniae isolated before treatment, 22 (12.9%) had reduced susceptibility to penicillin, 5 (2.9%) of them penicillin resistant (minimum inhibitory concentration > or = 2 microg/mL). At the posttreatment visit, the overall eradication rates of pathogens isolated from microbiologically evaluable patients were 88.7% (134/151), 89.9% (134/149), and 95.7% (134/140) in the respective treatment groups (P = 0.031, cefditoren 200 mg vs cefpodoxime). Eradication rates of S pneumoniae were 93.8% (45/48), 95.7% (45/47), and 95.6% (43/ 45) in the respective treatment groups; those of Haemophilus influenzae were 90.2% (46/51), 97.7% (43/44), and 97.4% (37/38). The rates of resolution and/or improvement in clinical signs and symptoms were comparable between groups. The study drugs were well tolerated, with 1.7%, 2.5%, and 1.4% of patients in the respective groups discontinuing study drug prematurely due to a treatment-related adverse event, the majority of these associated with the digestive system., Conclusion: The results of this study suggest that cefditoren may have a role in the treatment of CAP in ambulatory patients.

Abilities of amoxicillin-clavulanate, cefpodoxime, cefprozil, azithromycin, and clarithromycin to select resistant mutants of Haemophilus influenzae were tested by multistep and single-step methodologies. For multistep studies, 10 random strains were tested: 5 of these were beta-lactamase positive. After 50 daily subcultures in amoxicillin-clavulanate, MICs did not increase more than fourfold. However, cefprozil MICs increased eightfold for one strain. Clarithromycin and azithromycin gave a >4-fold increase in 8 and 10 strains after 14 to 46 and 20 to 50 days, respectively. Mutants selected by clarithromycin and azithromycin were associated with mutations in 23S rRNA and ribosomal proteins L4 and L22. Three mutants selected by clarithromycin or azithromycin had alterations in ribosomal protein L4, while five had alterations in ribosomal protein L22. Two mutants selected by azithromycin had mutations in the gene encoding 23S rRNA: one at position 2058 and the other at position 2059 (Escherichia coli numbering), with replacement of A by G. One clone selected by clarithromycin became hypersusceptible to macrolides. In single-step studies azithromycin and clarithromycin had the highest mutation rates, while amoxicillin-clavulanate had the lowest. All resistant clones were identical to parents as observed by pulsed-field gel electrophoresis. The MICs of azithromycin for azithromycin-resistant clones were 16 to >128 micro g/ml, and those of clarithromycin for clarithromycin-resistant clones were 32 to >128 micro g/ml in multistep studies. For strains selected by azithromycin, the MICs of clarithromycin were high and vice versa. After 50 daily subcultures in the presence of drugs, MICs of amoxicillin-clavulanate and cefpodoxime against H. influenzae did not rise more than fourfold, in contrast to cefprozil, azithromycin, and clarithromycin, whose MICs rose to variable degrees.

The stability of cefcapene and cefpodoxime, oral antibacterial cephalosporins, toward different classes of beta-lactamases was evaluated. For the class A beta-lactamases, TEM-1, SHV-1, and NMC-A, only the steady-state kinetic parameter ( k(cat)/ Km) values were calculated (3100 - 1.1 x 10(7) M(-1) x s(-1)), because these enzymes have very high Km values for cefpodoxime and cefotaxime. As for class B beta-lactamases L1, IMP-1, and CcrA, in general, similar k(cat)/ Km values were obtained. However, regarding class C beta-lactamases from Enterobacter cloacae, Escherichia coli, Pseudomonas aeruginosa, and Citrobacter freundii, we found major differences in stability between the two compounds. Cefpodoxime acted as a good substrate for the class C beta-lactamases, except for the enzyme from E. cloacae; its k(cat) and Km values were successfully calculated ( k(cat)/ Km, 1.8 x 10(5) - 1.2 x 10(7) M(-1) x s(-1)). On the other hand, cefcapene acted as a poor substrate or an inactivator for class C beta-lactamases; its k(2)/ K value was successfully calculated (8.7 x 10(5) - 7.0 x 10(6) M(-1) x s(-1)). In addition, k(3) values were determined for beta-lactamases from P. aeruginosa (2.3 x 10(-2) x s(-1)) and C. freundii (2.1 x 10(-1) x s(-1)). Even though these values could be calculated, transient inactivation as an enzyme reactivation reaction for all these enzymes was observed. These findings suggest the potential of cephem compounds as inhibitors of class C beta-lactamases.

Background: The excretion of medicated drugs into saliva may disturb the oral environment and antibiotic excretion into saliva appears to be regulated by many factors that have not been fully explored., Methods: Excretion of four cephem antibiotics into saliva was examined in healthy volunteers and rats, using high-performance liquid chromatography, and the relationship between excretion levels and plasma protein-binding activities of the antibiotics was investigated., Results: Following addition of 50 microgram/ml of each antibiotic to human plasma, protein binding rates (PBRs) of cefuzonam (CZON, molecular weight (MW): 535.58), cefotaxime (CTX, MW: 477.45), flomoxef (FMOX, MW: 518.45) and cefozopran (CZOP, MW: 551.99) were 87.8 +/- 1.2, 70.8 +/- 0.8, 36.2 +/- 0.5 and 8.3 +/- 0.3%, respectively. In rat plasma, PBRs of the four antibiotics were 94.0 +/- 0.5, 62.1 +/- 1.4, 54.0 +/- 0.8 and 6.0 +/- 0.8%, respectively. Similar PBRs were observed when the antibiotic concentration was increased to 100 and 200 microgram/ml. CZOP was most rapidly excreted into saliva and had the highest concentration in saliva among the tested antibiotics, while the plateau level of CZON was the lowest. The excreted levels of each antibiotic in saliva, when locally perfused through the rat facial artery, were inversely associated with each PBR. Similarly, the ratios of antibiotic concentration in saliva to rat plasma were almost constant for each antibiotic, revealing an inverse relationship with PBRs., Conclusion: These results appear to indicate that low molecular weight antibiotics are excreted into saliva through passive diffusion, inversely relating to their PBRs, and that high concentrations of antibiotics in the saliva have the potential to change the oral ecological environment.

To investigate the effects of gastrectomy on the absorption of drugs, the blood concentrations of the active moieties, cefcapene (CCAP) and ceftizoxime (CTIZ), were determined in 36 gastrectomized patients after oral administration of cefcapene pivoxil (CCAP-PI) and AS-924, prodrug type cephem antibiotics with different solubility-profiles. In patients with gastrectomy, the C(max) and AUC for CCAP-PI whose solubility depended on the acidity of gastric juice, were lower than in the controls; whereas those for AS-924 were comparable with values in the control group. The T(max) was affected by the extent of gastrectomy; the T(max) value was the lowest in patients who had undergone total gastrectomy Roux-Y, followed by Billroth II and Billroth I procedure of subtotal gastrectomy. These results indicate the need to select drugs and to instruct gastrectomized patients regarding dosage and administration, taking the pharmacokinetics of drugs into consideration.

We investigated the effect of infusion rate and experimental renal failure on the pharmacodynamics of cefoselis (CFSL)-induced seizures. As an animal model of CFSL-induced seizures, male Wistar rats received an intravenous infusion of CFSL at one of three different rates (1.4-5.8 g/h/rat) until the onset of maximal seizures (which occurred after 8.0 to 36.0 min of infusion). Samples of cerebrospinal fluid (CSF), blood (for serum), and brain were obtained immediately after stopping infusion of CSFL. The serum concentration of CFSL at the onset of seizures increased with increasing infusion rate, but brain and CSF concentrations of CFSL at the onset of seizures were not affected by the infusion rate. Ureter-ligated (UL) and control rats received an intravenous infusion of CFSL at 1.4 g/h/rat until the onset of seizures. Then the same procedure as used to determine the effect of infusion rate on the concentrations of CFSL was carried out. Renal failure was associated with a significant decrease in the amount of CFSL required to induce seizures. Serum, brain, and CSF concentrations of CFSL in UL rats were significantly lower than those in control rats. These results indicate that the experimental strategy and animal model in this investigation would be useful to assess the effects of diseases and other variables on the pharmacodynamics of CFSL-induced seizures and that renal failure is one of the risk factors for neurotoxicity of CFSL.

Killing curves and a sepsis model were performed with Streptococcus pneumoniae strains (MICs of penicillin = 0.01, 1, 2 and 4 mg/L) to assess the in vivo effect of in vitro early bactericidal activity. Optimal bactericidal concentration (OBC) was defined as the minimal concentration needed to obtain the maximal bactericidal activity during the sampling time for colony counting in killing curves. Animals were treated with amoxycillin, cefuroxime or cefpodoxime every 8 h for 48 h, with doses ranging from 2.5 to 50 mg/kg. ED100 (minimal antibiotic dose obtaining a 100% survival) was used as efficacy endpoint. Cmax/MIC, AUC/MIC and deltaT >MIC did not accurately predict efficacy against the most resistant strains, deltaT >OBC being the most predictive efficacy parameter indicating the in vivo effect of early bactericidal activity. Lower deltaT >OBC values for amoxycilin vs oral cehalosporins were needed for efficacy. The higher early bactericidal activity of amoxycillin may explain its higher in vivo efficacy.

We used a Vitek custom card to detect cefpodoxime MIC of--2 mg/L as a screen for extended-spectrum beta-lactamase (ESBL) production in E. coli and Klebsiella spp. Of 2873 organisms tested, 60 were screen positive, but only 3 were confirmed to be ESBL producers. Cefpodoxime is believed to be a sensitive screen for ESBL production, but a more specific test is desirable.

Clinical effects of cefoselis (CFSL) on various infections and prevention of postoperative infections in the field of obstetrics and gynecology were investigated with a total of 100 patients of 8 facilities in Yamagata and the following results were obtained: 1. For the patients (n = 70) who received the treatment with CFSL at 2 g/day for 5 days to prevent postoperative infections, the treatment was effective for such infections in 68 of 69 (98.6%) except one to whom the treatment was discontinued during the course. 2. For the patients with infections (n = 30) who were treated with CFSL at 2-4 g/day for 5-7 days, the treatment was markedly effective in 8/30 (26.7%), effective in 21/30 (70%) and not effective in 1/30 (3.3%). The overall rate of efficacy was 29/30 (96.7%). Based on the clinical effects for each isolate, the bacteriological efficacy was evaluated as 29/29 and the rate of bacterial eradication for each isolate was 23/29 (79.3%). 3. Laboratory test revealed liver functional abnormalities in one patient and eruption, a subjective/objective symptom caused by CFSL was noted in two patients. These results suggest that CFSL is effective for various infections in obstetric and gynecologic field and also the prevention of postoperative infections.

The Oxoid combination disk method for detecting extended-spectrum beta-lactamases (ESBLs) depends on comparing the inhibition zones of cefpodoxime (10-microg) and cefpodoxime-plus-clavulanate (10- plus 1-microg) disks. The presence of clavulanate enlarged the zones for all of 180 ESBL-producing klebsiellae by >/=5 mm, whereas zones for cefpodoxime-susceptible isolates and cefpodoxime-resistant isolates with AmpC and K1 beta-lactamases were enlarged by

Background: Although postoperative infections continue to be a major problem in gynecologic surgery, there is still no consensus on the efficacy of antibiotic prophylaxis., Methods: This prospective randomized trial was conducted to investigate the prevention of major operating site infections after nonlaparotomy surgery, with treatment regimens as follows: the first group of patients received 2 g of intravenous cefotiam dihydrochloride (CTM) on the induction of anesthesia, while the second group received 100 mg of oral cefpodoxime proxetil (CPDX- PR) twice daily, from day 0 to day 2., Results: Nineteen of the 207 patients enrolled developed postoperative infections diagnosed by our simple criteria for postoperative infection. The frequency of febrile morbidity was not significantly less in patients who received CTM (9 cases; 8.6%) as compared with those in the CPDX-PR group (10 cases; 9.8%) (p = 0.56)., Conclusion: The administration of oral CPDX-PR (100 mg, twice daily, for 3 days) appears to be a safe, cost-saving, convenient prophylaxis which reduces overall expense., (Copyright 2000 S. Karger AG, Basel.)

Cefpodoxime is an oral third-generation cephalosporin used for the treatment of acute upper-respiratory tract infections caused by susceptible bacteria in children. Although not indicated for the treatment of bacterial meningitis, it is used to treat other infections produced by organisms associated with meningitis and may obscure the result of cerebrospinal fluid (CSF) cultures in children who develop meningitis while receiving oral antibiotics if sufficient concentrations are achieved in the CSF. This study evaluated the disposition of cefpodoxime and penetration into CSF in piglets. Fifteen Landacre-Camborough cross piglets (10-20 days old) received cefpodoxime proxetil oral suspension (10 mg/kg). Repeated plasma and CSF samples were collected over 24 hours for quantitation of cefpodoxime by HPLC. Pharmacokinetic analysis was performed on both plasma and CSF data. The plasma concentration versus time data for cefpodoxime were best characterized using a one-compartment model with first-order absorption. The mean (+/- SD) pharmacokinetic parameters for Cmax, tmax, and AUC0-infinity were 23.3 +/- 12.9 mg/L, 3.9 +/- 1.4 h, and 237 +/- 129 mg/L.h, respectively. CSF/plasma ratios for AUC0-infinity demonstrated a mean cefpodoxime penetration of approximately 5%. CSF penetration of cefpodoxime was evident following a single oral dose of cefpodoxime proxetil suspension. Despite the small percentage of total cefpodoxime dose distributing into the CSF, the resultant concentrations approached or exceeded the MIC90 for many bacterial pathogens considered susceptible to cefpodoxime. Accordingly, clinicians should use caution in the interpretation of CSF cultures in patients who develop clinical signs and symptoms consistent with meningitis and who have been previously treated with cefpodoxime.

The novel 4(th) generation cephalosporin FK037 was in vitro compared to cefepime and cefpirome on 563 multiresistant nosocomial isolates including methicillin-susceptible (MSSA) and methicillin-resistant Staphylococcus aureus (MRSA). Their time-kill effect was studied on MSSA, Escherichia coli, Klebsiella pneumoniae, and isolates of Enterobacter cross-resistant to cefotaxime, ceftriaxone, and to ceftazidime, their interaction with amikacin being also evaluated on the latter isolates. Results revealed that FK037 possessed a superior antistaphylococcal activity on MSSA isolates to both other compounds being however equal active to cefepime and cefpirome on multiresistant enterobacteriaceae. Synergy was documented between 4(th) generation cephalosporins and amikacin on K. pneumoniae and on Enterobacter spp. cross-resistant to 3(rd) generation cephalosporins. In the latter species 4(th) generation cephalosporins remained inactive. The presented results support the need of clinical studies with FK037 as monotherapy for nosocomial infections based on the local surveillance data of the level of antimicrobial resistance of each hospital.

Ceftizoxime (CZX), a parenteral cephalosporin, has potent and broad antibacterial activity. To improve its oral absorption, we synthesized a series of monofunctional and bifunctional prodrugs of CZX. In rabbits, urinary recovery after oral administration of CZX was improved by esterification of the carboxyl group at the C-4 position with various lipophilic moieties (monofunctional prodrugs), and was further increased by introduction of a hydrophilic L-alanine to the amino group on the thiazole ring at the C-7 position (bifunctional prodrugs). Least-squares analysis showed good parabolic correlations between log P and urinary recovery for monofunctional and bifunctional prodrugs, respectively. AS-924, a bifunctional prodrug with a pivaloyloxymethyl and L-alanyl moiety had the best balance of lipophilicity and water-solubility for oral absorption among the prodrugs synthesized.

Antimicrobial activities of cefetamet (CEMT) against clinically isolated strains from patients with community acquired respiratory tract infections were investigated in comparison with those of other oral beta-lactam antibiotics during the period from January to March, 1998. The results are summarized as follows; 1. CEMT showed strong antimicrobial activities against three major pathogens causing community acquired respiratory tract infections, Streptococcus pyogenes, Streptococcus pneumoniae and Haemophilus influenzae. However, antimicrobial activities of CEMT against penicillins (PCs)-intermediate S. pneumoniae (PISP) and PCs-resistant S. pneumoniae (PRSP) were slightly weaker than those of some of the reference antibiotics. 2. No chronological changes of CEMT-MIC level were observed in the antimicrobial activities against S. pyogenes, H. influenzae, Moraxella subgenus Branhamella catarrhalis or Klebsiella pneumoniae subsp. pneumoniae. In contrast to this, due to the increase of PISP and PRSP strains, resistance to CEMT appears increasing with time.

Purpose: This paper reports experimental data on the ESR identification of four irradiated cephalosporins (cefpodoxime, cefsulodin, cefixime and ceftizoxime)., Materials and Methods: Equations to describe the ESR curves versus the dose and storage time were developed using mathematical procedures., Results: Limits of detection (LOD) and limits of quantification (LOQ), estimated on the basis of the S/N ratios are 1.0+/-0.5 kGy and 2.5+/-0.5 kGy respectively. The yield of free radicals are in the range 4.6 10(19) - 2.2 10(20) radicals mol(-1) (G values from 0.1 to 0.4). Besides a very unstable situation (cefsulodin), the time limit of detection of free radicals after storage ranges from about 1 year to over 2 years. These time intervals are comparable with the shelf-life of the antibiotics and to the time limits found for 10 other cephalosporins described previously. Apart from qualitative detection, ESR spectrometry can be used for dose estimation. Exponential loss of ESR signal (first-order reaction) correlates well with the data., Conclusion: Given the sensitivity of ESR spectrometry, this experimental technique is promising for identification of irradiated cephalosporins.

The levels of degradation of cefetamet pivoxil (CAT), cefuroxime axetil (CAE), and cefpodoxime proxetil (CPD) in 0.6 M phosphate buffer (pH 7.4) and human intestinal juice (pH 7.4) at 37 degreesC over 24 h were compared. Significant differences in the time courses of degradation and in the patterns of degradation products were observed. (i) The relative proportions of the Delta2- and Delta3-cephalosporins were roughly reversed in the two incubation media. In phosphate buffer, the major degradation product was the Delta2-cephalosporin (CAT = 61%; CAE = 74%; CPD = 85%), while in intestinal juice it was the Delta3-cephalosporin (CAT = 86%; CAE = 75%; CPD = 87%). (ii) Generally, the degradation of the prodrug esters progressed faster in intestinal juice than in phosphate buffer (e.g., for CAT the half-lives [t1/2s] were 0.78 and 4.3 h, respectively). (iii) The two diastereoisomers of CAE and CPD were degraded at different rates in intestinal juice (for the CAE diasteroisomers, t1/2s = 0.37 and 0.93 h; for the CPD diastereoisomers, t1/2s = 0.18 and 0.98 h) but were degraded at similar rates in phosphate buffer (for the CAE diastereoisomers, t1/2 = 1.6 h; for the CPD t1/2 diastereoisomers, = 2.2 h). It is concluded that (i) the Delta2 isomerization does not significantly affect the bioavailability of prodrug esters since enzymatic hydrolysis in the intestinal fluid proceeds mainly to the active Delta3-cephalosporin and (ii) the high degree of stereoselectivity of the enzymatic ester hydrolysis should make it possible to increase the bioavailabilities of certain prodrug esters (CAE, CPD) by using the more stable diasterioisomer.

An open-labeled and randomized trial was conducted to compare the efficacy and safety of once daily cefpodoxime proxetil suspension (10mg/kg/day) and thrice daily cefaclor (45mg/kg/day) in the treatment of acute otitis media in children. A total of 57 children aged from 6 months to 9 years were enrolled; 23 were treated with cefpodoxime and 34 with cefaclor. Satisfactory clinical outcome, either cure or improvement, was achieved at the end of treatment in 90% of patients in the cefaclor group and 95% of patients in the cefpodoxime group (p > 0.05). Clinical recurrence was identified at the follow-up visits in one case of the cefaclor group (3%), and none in the cefpodoxime group (p > 0.05). These drugs were well tolerated by 14/21 (67%) in the cefpodoxime-treated group and 27/32 (84%) in the cefaclor-treated group. The incidence of adverse events was slightly higher in the cefpodoxime group than in the cefaclor group, however the difference did not reach statistical significance (p > 0.05). The daily cost of once-daily cefpodoxime was lower than that of thrice-daily cefaclor. We conclude that cefpodoxime administered once daily is as effective and safe as cefaclor administered thrice daily in the treatment of acute otitis media in children. The less dosing frequency and lower daily price of cefpodoxime provide additional benefits.

Background: Cefpodoxime, an oral third generation cephalosporin antibiotic, is used for the treatment of acute upper respiratory tract infection caused by susceptible bacteria in children 5 months to 12 years of age. We report the results of a randomized two-way crossover study designed to characterize the disposition of a single dose (10 mg/kg) of cefpodoxime proxetil oral suspension in children, under fed and fasted conditions., Methods: Seventeen children (8.4 months to 12.2 years old, seven female) participated in this study. Each subject received a single 10-mg/kg dose of cefpodoxime proxetil oral suspension, after a predose fast and again coadministered with food. Repeated blood samples (n=10) were obtained during 12 h postdose and cefpodoxime was quantified from plasma by high performance liquid chromatography. Plasma concentration vs. time data were curve fit for each subject with a nonlinear weighted least squares algorithm, and pharmacokinetic parameters were determined from the polyexponential estimates., Results: Cefpodoxime disposition was best characterized using a one-compartment open model with first order absorption. The area under the plasma concentration vs. time curve, Cmax and Ke were not significantly different between fed and fasted conditions. However, Tmax was significantly prolonged (fed=2.79+/-1.10 h vs. fasted=1.93+/-0.54 h) and Ka was significantly smaller (fed=0.42+/-0.14 h(-1) vs. fasted=0.81+/-0.72 h(-1)) in the fed state., Conclusions: Administration of cefpodoxime in the presence of food affected the rate but not the extent of absorption. Cefpodoxime proxetil oral suspension can be administered without regard to meals in children 6 months to 12 years of age.

(1) Oral cefpodoxime, a third-generation cephalosporin, has a reduced treatment duration for recurrent pharyngitis; but this is based on a single unblinded trial. (2) At the end of the 5-day treatment during the trial, the clinical efficacy of cefpodoxime was no different from that of a 10-day course of penicillin V or the amoxicillin + clavulanate combination. (3) The relapse rate at 6 months is uninterpretable because many patients were lost to follow-up and were not included in the statistical analysis. To our knowledge the second indication granted for cefpodoxime, chronic tonsillitis, has not been validated in clinical trials. (4) Trivialising cefpodoxime may induce antibiotic resistance.

The serum bactericidal activity of three oral cephalosporins was studied in 12 volunteers, after administration of single doses of cefuroxime axetil 250 mg, cefixime 200 mg, cefixime 400 mg and cefetamet pivoxil 500 mg. Serum bactericidal activity against clinical isolates of Streptococcus pyogenes, Streptococcus pneumoniae, Haemophilus influenzae and Klebsiella pneumoniae was measured by a standardized microdilution method. Cefuroxime axetil demonstrated the best bactericidal activity against Gram-positive organisms and cefixime was the most bactericidal against Gram-negative bacteria.

Clinical efficacy of 3rd generation cephalosporins i.e. oral cefpodoxime and parenteral ceftriaxone was studied in the treatment of children with oncohematologic pathology. Cefpodoxime proved to be efficient in cases of moderate infectious complications in regard to the respiratory tracts. The oral administration of the drug provided its usage in outpatients. Ceftriaxone had a favourable effect in the treatment of children with more severe processes as a rule at the background of agranulocytosis and a lower immune response often with a tendency to generalization. No side effects of the cephalosporins were observed.

We investigated clinical and bacteriological effects of cefetamet pivoxil (CEMT-PI) in community-acquired respiratory tract infections and obtained the following findings. That method was approximately equal to that of investigation in 1994. 1. Of the 431 respiratory tract infection cases that were treated with CEMT-PI according to a same protocol at a total of 41 institutions in Tokyo, Kanagawa-ken, Saitama-ken and Chiba-ken from January to the beginning of March 1996. Outpatients accounted for 98.1% of the subjects. Regarding genders to patients, slightly more females (52.6%) than males were included. Diagnoses given to these patients included pharyngo-laryngitis (53.5%), tonsillitis (20.4%) and acute bronchitis (19.1%). 2. We investigated clinical efficacy rates (the ratio of those excellent + good) classified by diseases. The improvement rates of pharyngo-laryngitis, tonsillitis and acute bronchitis were more than 85.0%. Other cases were small in number. That of chronic bronchitis-acute increasing change for the worse was 66.7%, pneumonia was 50.0% and bronchiectasis infection was 16.7%. It was not studied that clinical efficacy rates among those who were treated with 1 CEMT-PI tablet twice and among those who were given 2 tablets twice were significant level. 3. For the bacteriological study, a written material describing the method of collecting specimens, storage and transport in detail was distributed to the above mentioned institutions. The isolation and identification of suspected causative bacteria, determination of minimum inhibitory concentrations (MICs) and investigation of beta-lactamase production were conducted all together at section of studies, Tokyo Clinical Research Center. Suspected causative bacteria were detected from 274 (63.6%) cases. They included 88 strains of Haemophilus influenzae, 47 strains of Streptococcus pneumoniae, 42 strains of Streptococcus pyogenes, 20 strains of Moraxella subgenus Branhamella catarrhalis and 17 strains of Klebsiella pneumoniae subsp. pneumoniae. Suspected causative bacteria classified by diseases were S. pyogenes (tonsillitis), S. pneumoniae (acute bronchitis and secondary infection of chronic respiratory infection) and H. influenzae (pharyngo-laryngitis), and the detection frequency of those was high. The clinical efficacies (the ratio of improvement) classified by suspected causative bacteria were 84.4% against organism that was indicating CEMT and were 69.2% against organism that was not indicating CEMT.

The synthesis and in vitro antibacterial activity of 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido] cephalosporins bearing various 2-alkyl-3-aminopyrazolium groups at the 3-position are described. Antibacterial activity against MRSA was affected by the nature of the substituent at the 2-position on the 3'-aminopyrazolium groups. Among the cephalosporins prepared in this study, 7 beta-[(Z)-2-(2-aminothiazol-4-yl)-2-methoxyiminoacetamido]-3-[3-am ino-2-(2 -hydroxyethyl)-pyrazolio]methyl-3-cephem-4-carboxylate sulfate (23e, FK037) showed extremely potent broad-spectrum activity against both Gram-positive bacteria including MRSA, and Gram-negative bacteria including Pseudomonas aeruginosa. In particular, the in vivo activity against MRSA of FK037 was the highest of all the beta-lactam antibiotics tested.

A randomized controlled clinical study of cefetamet pivoxil (CAT) compared with cefixime (CFX) was conducted to evaluate its safety and efficacy in treating bacterial infections. 99 patients suffering from respiratory and urinary tract infections were enrolled in the study. 10 patients were excluded within the first 72 hrs after initiation of the study. 55 and 54 were evaluated for the safety of CAT and CFX respectively. 51 patients in the CAT group and 48 patients in the CFX group were evaluated for the efficacy. The doage of CAT was 250-500 mg and CFX was 200 mg, twice daily orally for 7-10 days. The results showed that the clinical efficacy rates of CAT and CFX were 94.1% (48/51) and 91.7% (44/48), the bacterial clearance rates were 95.3% and 95.1%, respectively. Adverse drug reactions occurred in 9.1% and 7.4% in the two groups respectively. The study demonstrated that there were no satistical differences between the two groups with respect to clinical efficacy, bacterial clearance and adverse reactions.

Study Objectives: To determine the time above minimum inhibitory concentration (T > MIC) and serum bactericidal activity of five oral cephalosporins against two strains of Haemophilus influenzae., Design: Randomized, crossover study., Setting: University-associated research center., Subjects: Ten healthy volunteers., Interventions: Each subject received a single dose of cefpodoxime 200 mg, cefuroxime 500 mg, cefaclor 500 mg, cefprozil 500 mg, or loracarbef 400 mg each week for 5 weeks. Blood for serum levels was obtained at time zero and 1, 2, 3, 4, 6, 8, and 12 hours after each dose., Measurements and Main Results: Cefpodoxime produced serum concentrations above the MIC for more than 90% of the time for both beta-lactamase-negative and -positive strains of H. influenzae. Moreover, it had serum bactericidal activity for 12 hours against both isolates. Cefuroxime was the second most active cephalosporin, with serum concentrations above the MIC of both isolates for 60% of the time. Cefuroxime provided serum bactericidal activity for 12 hours against the beta-lactamase-negative strain and 6 hours against the beta-lactamase-positive strain of H. influenzae. Even though the T > MIC was less than 50% of the study period for the other cephalosporins, all but cefaclor provided serum bactericidal activity for 12 hours against the beta-lactamase-negative isolate. Cefaclor provided measurable serum bactericidal activity for only 3 hours. The duration of serum bactericidal activity of cefprozil, loracarbef, and cefaclor against the beta-lactamase-positive isolate was 4, 2, and 0 hours, respectively., Conclusion: Cefpodoxime was the most active cephalosporin studied based on T > MIC and serum bactericidal activity against isolates of H. influenzae.

Cefpodoxime proxetil is a new orally administered prodrug which is absorbed and de-esterified by the intestinal mucosa to release the third-generation cephalosporin, cefpodoxime, and which is undergoing in vitro and in vivo evaluations. Using the standard agar dilution method, we compared the in vitro activity of this drug with other oral cephalosporins and quinolones against 637 recent clinical isolates from Kaohsiung Veterans General Hospital in Taiwan. Against Escherichia coli and Klebsiella pneumoniae, cefpodoxime showed excellent activity, inhibiting over 90% of these isolates at 1 mg/l. Like other oral drugs of its class, it had little activity against Pseudomonas aeruginosa and Acinetobacter spp. Against Haemophilus influenzae, irrespective of beta-lactamase production, its activity was similar to comparative drugs. Against methicillin-susceptible Staphylococcus aureus, cefpodoxime showed moderate activity, inhibiting 90% of these isolates at 4 mg/l, whereas it was inactive against methicillin-resistant S. aureus. However, all cephalosporins have shown little in vivo activity against methicillin-resistant S. aureus regardless of in vitro results. Cefpodoxime was inactive against Enterococcus spp. Against other streptococci, its activity was similar to other oral cephalosporins and quinolones tested. The results of this in vitro study indicated that oral administration of cefpodoxime should be an ideal agent in the empirical outpatient treatment for community-acquired cutaneous, respiratory and urinary tract infections.

The activity, pharmacokinetic and pharmacodynamic parameters of 5 oral beta-lactams have been compared against 400 penicillin-resistant Streptococcus pneumoniae (PRSP) isolated in 9 European countries. All the data have been calculated for the highest recommended oral dosage in France. Amoxicillin was by far the most effective antibiotic when considering its intrinsic activity (96% of the PRSP inhibited at 2 mg/l), the inhibitory quotient (100% of the PRSP > 1 vs 69.2% for cefuroxime) or a time above MIC > 40% which best correlates with clinical results (96% for amoxicillin vs < 25% for the cephalosporins).

In order to evaluate antimicrobial activity of cefetamet (CEMT), minimum inhibitory concentrations (MICs) of CEMT and control drugs were determined against Gram-negative rods mainly from complicated urinary tract infections examined in our laboratory from April to September of 1994. The results are summarized as follows; 1. The obtained strains were Citrobacter diversus 20, Citrobacter freundii 30, Enterobacter aerogenes 20, Enterobacter cloacae 30, Serratia marcescens 30, Proteus mirabilis 30, Proteus vulgaris 20 and Morganella morganii 30 strains, a total of 210 strains. 2. Excluding some resistant strains, the MIC-distribution showed showed that CEMT had strong antimicrobial activities against those strains from the MIC-distribution of this investigation. Compared to reports on CEMT in 1989, the MIC80 of CEMT in this investigation against clinical isolates were similar. The MIC50's of CEMT against E. aerogenes, S. marcescens, P. mirabilis, P. vulgaris and M. morganii in the previous examination were equal to or similar to the current results, but the MIC50's against C. freundii and E. cloacae were lower than the value of this report. The detection frequency of highly resistant strains of C. freundii and E. cloacae to cefteram and cefixime were similar to that of CEMT-resistant strains. Multiple drug resistant strains, among these bacterial species seemed to be increasing. 3. Compared to oral antibacterial agents of oxime cephems that were used in the past, CEMT showed higher peak values of urinary excretion concentration and higher blood levels were sustained for a longer period of time. CEMT-PI will be effective against urinary tract infections.