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PubMed1995

Antimicrobial susceptibility of subgingival bacterial flora in cats with gingivitis.

The aerobic and anaerobic flora from gingival pockets of 40 cats with established gingivitis were cultured. The susceptibility of each isolate to four antimicrobial agents currently approved for use in cats (amoxicillin-clavulanic acid; clindamycin; cefadroxil; enrofloxacin) was determined. Amoxicillin-clavulanic acid (Clavamox) had the highest in-vitro susceptibility against all isolates (92%) and all anaerobes (99% [co-equal with clindamycin]) tested; enrofloxacin (Baytril) had the highest in-vitro susceptibility against all aerobes (90%) tested.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed1994

Cefuroxime axetil in the treatment of sinusitis. A review.

Cefuroxime axetil is a beta-lactamase-stable, second-generation, oral cephalosporin that penetrates sinus tissue in concentrations exceeding the MIC90 values (the minimum concentration of drug needed to inhibit the growth of 90% of an isolate of a particular microorganism) for pathogens most commonly associated with acute sinusitis, including Streptococcus pneumoniae and Haemophilus influenzae. A review of all clinical data published to date demonstrates that cefuroxime axetil has been evaluated in the treatment of acute sinusitis and acute exacerbations of chronic sinusitis ("acute-on-chronic sinusitis") in 18 clinical trials involving 1516 assessable patients. In 12 randomized, comparative trials, the rates of satisfactory clinical outcomes (cure or improvement, 79% to 100%) and bacteriologic eradication (84% to 100%) reported with the use of 250 mg of cefuroxime axetil twice daily were similar to those observed with the use of amoxicillin, amoxicillin/clavulanate potassium, cefaclor, cefadroxil, cefixime, clarithromycin, and doxycycline. In these comparisons, no antibiotic demonstrated any therapeutic advantages over cefuroxime axetil regarding time to symptom abatement. Cefuroxime axetil was at least as well tolerated as the other antibiotics. Overall, the role of cefuroxime axetil in the treatment of sinusitis appears to be as one of the broad-spectrum antibiotics that can be used for infections due to the most commonly implicated sinus pathogens, especially those due to the increasing number of relatively penicillin-resistant strains of S pneumoniae and beta-lactamase-producing strains of H influenzae and Moraxella catarrhalis.

Acute Disease↗
PubMed1997

Strategies for managing group A streptococcal pharyngitis. A survey of board-certified pediatricians.

OBJECTIVE: To assess the management strategies and knowledge of board-certified pediatricians regarding group A beta-hemolytic streptococcal (GABHS) pharyngitis. DESIGN: Survey of 1000 US pediatricians in 1991, chosen randomly from the membership of the American Academy of Pediatrics. The survey included questions related to 2 clinical scenarios, respondent demographics, and knowledge of streptococcal pharyngitis. SUBJECTS: Pediatricians who treated patients with pharyngitis. Of the 690 surveys that were returned, 510 pediatricians treated patients with pharyngitis and were included in the data analysis. DATA ANALYSIS: Data were analyzed using Chi 2 statistics for categorical data and the Student t test for continuous variables. RESULTS: Antigen detection tests (ADTs) were used by 64% of the pediatricians; 85% used throat cultures. Strategies for diagnosing streptococcal pharyngitis were throat culture alone (38%), consider positive ADTs definitive and use throat culture when ADTs are negative (42%), ADT alone (13%), ADT and throat culture for all patients with pharyngitis (5%), and no tests for GABHS performed (2%). Thirty-one percent usually or always treated with antibiotics before test results were available. Only 29% of these "early treaters" always discontinued antibiotics when tests did not confirm the presence of group A streptococci. The drug of choice for treatment was penicillin (73%); another 26% preferred a derivative of penicillin, particularly amoxicillin. Many pediatricians altered their management when a patient had recurrent streptococcal pharyngitis. Nearly half of the respondents would use a different antibiotic than they used for routine acute streptococcal pharyngitis. They most often changed to erythromycin (25%), cefadroxil (23%), or amoxicillin-clavulanate (20%). Follow-up throat culture was obtained by 51% of pediatricians after treatment of recurrent streptococcal pharyngitis. A patient with chronic carriage of GABHS and symptoms of pharyngitis would be treated with an antibiotic by 84%; most (62%) would use a penicillin. Other choices were cephalosporins (19%), erythromycin (12%), clindamycin (3%), or rifampin plus penicillin (3%). Tonsillectomy was recommended for symptomatic carriers by 31% of respondents. Carriers without symptoms were less likely to be treated with antibiotics (23%) or referred for tonsillectomy (21%). CONCLUSIONS: Most surveyed board-certified pediatricians managed acute GABHS pharyngitis appropriately, but 15% to 20% used diagnostic or treatment strategies that are not recommended. There was lack of a consensus about the management of recurrent GABHS pharyngitis and chronic carriage of GABHS.

Acute Disease↗
PubMed1998

Carrier-mediated intestinal absorption of valacyclovir, the L-valyl ester prodrug of acyclovir: 1. Interactions with peptides, organic anions and organic cations in rats.

The mechanism of intestinal transport of valacyclovir (VACV), the L-valyl ester prodrug of acyclovir, was investigated in rats using an in situ intestinal perfusion technique. VACV demonstrates an oral bioavailability that is three to five time greater than acyclovir, concentration dependent, and saturable in humans. Homogenate and perfused buffer stability results demonstrated that VACV was increasingly unstable with increasing pH. VACV was converted to ACV in a concentration dependent manner during a single pass through the intestinal segment. Perfusions were performed at 37 degrees C, pH 6.5, and under iso-osmotic conditions (290 +/- 10 mOsm L-1). Intestinal outlet concentrations were corrected for VACV that was converted to ACV during the perfusion. The effective dimensionless intestinal permeability (P*e) of VACV was concentration dependent, saturable (intrinsic Km = 1.2 +/- 0.7 mM), and significantly reduced (p < 0.05) in the presence of peptide analogues (amoxicillin, ampicillin, cefadroxil, and cephradine), by the organic anion, p-amino hippuric acid and by the organic cation quinine. VACV transport was not inhibited by classical nucleoside competitive substrates or inhibitors or by valine. These results suggest that H(+)-oligopeptide, H(+)-organic cation, and organic anion transporters are involved in the small intestinal uptake of VACV. The permeability of VACV in the colon was very low, indicating that VACV is predominantly absorbed from the small intestine. VACV P*e was not altered in the presence of glucose-induced convective fluid flow, suggesting that carrier-mediated, transcellular uptake is the predominant absorption pathway of VACV in rat small intestine. Based on these results, the oral bioavailability of VACV appears to be significantly influenced by the preabsorptive conversion of VACV to the poorly absorbed ACV, by the involvement of multiple transporters in VACV small-intestinal uptake, and by the low permeability of VACV in the colon.

Acyclovir↗
PubMed1993

Bisubstrates: substances that interact with both, renal contraluminal organic anion and organic cation transport systems. II. Zwitterionic substrates: dipeptides, cephalosporins, quinolone-carboxylate gyrase inhibitors and phosphamide thiazine carboxylates; nonionizable substrates: steroid hormones and cyclophosphamides.

In order to test what chemical structure is required for a substrate to interact not only with the contraluminal organic anion (p-aminohippurate, PAH) transporter, but also with the organic cation (N1-methylnicotinamide, NMeN, or tetraethylammonium, TEA) transporter, the stop-flow peritubular capillary perfusion method was applied and app. Ki values were evaluated. Zwitterionic hydrophobic dipeptides not only interact with PAH but also with NMeN transport although with lower inhibitory potency (Ki,PAH = 0.2-1.4; Ki,NMeN 6-14 mmol/l). Amongst the zwitterionic cephalosporins, which all inhibit PAH transport, the amino cephalosporin analogue cefadroxil was identified to interact also with NMeN transport (Ki,PAH = 3.0, Ki,NMeN = 11.2 mmol/l). All zwitterionic naphthyridine and oxochinoline gyrase inhibitors tested inhibit NMeN transport with app. Ki,NMeN values between 1.2 mmol/l and 4.7 mmol/l; the naphthyridine analogues show a good inhibitory potency against PAH transport (Ki,PAH approximately 0.4 mmol/l), the piperazine-containing quinolone analogues have a moderate inhibitory potency (Ki,PAH = 1.1-2.5 mmol/l) and the piperazine-containing pipemidic acid did not inhibit PAH transport at all. Zwitterionic thiazolidine carboxylate phosphamides also interact with both transporters (app. Ki,PAH approximately 3.0; app. Ki,NMeN approximately 18.0 mmol/l). The nonionizable oxo- and hydroxy-group-containing corticosteroid hormones also interact with the two transporters. (a) An OH group in position 21 is necessary for interaction with the PAH transporter, but not for interaction with the TEA transporter. (b) Introduction of an OH group in position 17 alpha abolishes interaction with the TEA transporter, but has different effects with the PAH transporter. (c) Introduction of an OH group in position 6 abolishes interaction with both, the PAH and the TEA transporter. (d) A change of the side-group in position 11 of corticosterone from -OH to -H to = O enhances interaction with the PAH transporter but has no effect on the interaction with the TEA transporter. Nonionizable 4- or 5-androstene analogues inhibit both transporters with app. Ki between 0.16 mmol/l and 0.64 mmol/l, if the steroids are soluble in a concentration greater than 1 mmol/l. Nonionizable oxazaphosphorins with more than one chloroethyl group interact with the PAH transporter with app. Ki between 0.84 mmol/l and 4.9 mmol/l and with the NMeN transporter with app. Ki between 3.2 mmol/l and 18.7 mmol/l. Thus a substrate interacts with both transporters if it is sufficiently hydrophobic, possesses acidic and/or electron-attracting plus basic and/or electron-donating groups, or possesses several electron-attracting nonionizable groups (O, OH, Cl). A certain spatial arrangement of the interacting groups seems to be necessary.

Animals↗
PubMed1990

[Antibacterial activity and beta-lactamase stability of eleven oral cephalosporins].

Oral cephalosporins (cefixime, cefdinir, cefetamet, ceftibuten, cefpodoxime, loracarbef, cefprozil, cefuroxime, cefaclor, cefadroxil and BAY 3522) were compared by their antibacterial profile including stability against new beta-lactamases. Both activity and antibacterial spectrum of compounds structurally related to third generation parenteral cephalosporins (of the oximino class) were superior to established compounds. Activity against staphylococci was found to be highest for cefdinir, cefprozil and BAY 3522. Cefetamet, ceftibuten and cefixime demonstrate no clinically meaningful antistaphylococcal activity while the other compounds investigated demonstrate intermediate activity. The antibacterial spectrum was broadest for cefdinir and cefpodoxime. New oral cephalosporins are equally inactive as established compounds against Enterobacter spp., Morganella, Listeria, Pseudomonas and Acinetobacter spp., methicillin-resistant staphylococci, Enterococcus spp., penicillin-resistant pneumococci and anaerobes. New extended broad-spectrum betalactamases (TEM-3, TEM-5, TEM-6, TEM-7, SHV-2, SHV-3, SHV-4, SHV-5, CMY-1, CMY-2, and CTX-M) are active against the majority of oral cephalosporins. Ceftibuten, cefetamet, cefixime and cefdinir were stable against some of these enzymes even to a higher extent than parenteral cephalosporins. New oral cephalosporins should improve the therapeutic perspectives of oral cephalosporins due to their higher activity against pathogens marginally susceptible to established compounds (higher multiplicity of maximum plasma concentrations over MICs of the pathogens) and furthermore by including in their spectrum organisms resistant to established absorbable cephalosporins (e.g. Proteus spp., Providencia spp., Citrobacter spp., and Serratia spp.).

Administration, Oral↗
PubMedDate not supplied

Cefuroxime axetil versus ofloxacin for short-term therapy of acute uncomplicated lower urinary tract infections in women.

In a multicentre study 163 women with acute lower urinary tract infection were treated orally with either 125 mg cefuroxime axetil or 100 mg ofloxacin twice daily for three days. Both antimicrobial agents were generally well tolerated. Four patients in the group treated with cefuroxime axetil and two in the group treated with ofloxacin experienced adverse events. Clinical cure and improvement were registered in 56 of 66 (84.8%) and 59 of 62 (95.2%) of the evaluable patients treated with cefuroxime axetil and ofloxacin, respectively. Seven to nine days after therapy, bacteriuria (CFU < 10(3)/ml) had been eliminated in 53 of 66 (80.3%) and 57 of 64 (89.1%) of the evaluable patients receiving cefuroxime axetil and ofloxacin, respectively. The results were not statistically significantly different (p > 0.1). Pathogens present at baseline were eliminated by up to an MIC of 16 mg/l of cefuroxime axetil, independent of susceptibility to this agent. There was no difference with regard to efficacy and tolerance between patients treated with cefuroxime axetil and those treated with ofloxacin. On the basis of the MICs of six antimicrobial agents (cefuroxime, ofloxacin, cefadroxil, ampicillin, trimethoprim with and without sulfamethoxazole) determined for the pathogens isolated prior to therapy, resistance rates were lowest for cefuroxime (2.2%) and ofloxacin (3.4%).

Acute Disease↗
PubMed1990

Comparative in vitro activity of the new oral cephalosporin Bay v 3522 against aerobic and anaerobic bacteria.

The in vitro activity of the new oral cephalosporin Bay v 3522 against 229 aerobic and 330 anaerobic clinical isolates was determined using the agar dilution technique. For comparison, amoxicillin, amoxicillin/clavulanate, cefaclor, cefadroxil, cefuroxime, cephalexin, ciprofloxacin, clindamycin, co-trimoxazole, doxycycline, erythromycin and metronidazole (only anaerobic bacteria) were tested. Bay v 3522 was found to have high activity against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Streptococcus pneumoniae, Streptococcus pyogenes, Branhamella catarrhalis, Haemophilus influenzae, anaerobic cocci, Propionibacterium acnes, Clostridium perfringens and fusobacteria. When tested against a higher inoculum or using the broth dilution technique, the activity of Bay v 3522 showed little dependence on inoculum size and the bactericidal activity was similar to inhibitory activity in most bacterial groups. Bay v 3522 may be useful in the treatment of skin, soft tissue and respiratory tract infections. Clinical studies are thus warranted.

Aminoglycosides↗
PubMed2006

Demonstration of functional dipeptide transport with expression of PEPT2 in guinea pig cardiomyocytes.

The transporters PEPT1 and PEPT2 accept a broad spectrum of substrates including small, naturally occurring peptides and peptidomimetic drugs. This study aimed to investigate for the first time whether these transporters are expressed and active in isolated cardiomyocytes. PEPT1/PEPT2 expression in rat kidney (positive control), guinea pig kidney and cardiomyocytes were investigated by reverse transcription polymerase chain reaction. L-Glycyl-L-[(14)C]sarcosine (Gly-sar) uptake was characterised using freshly isolated suspensions of adult male guinea pig cardiomyocytes. PEPT2-specific primers recognised mRNA of appropriate size and sequence in cardiomyocytes and kidney, whilst PEPT1 was expressed in the kidney only. The initial uptake (30 s) of 200 microM Gly-sar was dependent on extracellular pH with a maximum at pH 6.0 (237.8 +/- 12.2 pmol/microl) and a minimum at pH 8.0 (72.1 +/- 13.4 pmol/microl, n = 6 +/- SE, p < 0.01, T test). The K (m) and V (max) of Gly-sar uptake at pH 6.0 were 495.5 +/- 69.6 microM and 1470.5 +/- 69.6 pmol microl(-1) min(-1). The addition of 10 mM fosinopril, cefadroxil, carnosine, cyclacillin or a variety of L-amino acid containing dipeptides/tripeptides significantly reduced Gly-sar uptake. Gly-sar uptake was not affected by 10 mM D-ala-D-ala, glycine or sarcosine. These results support the presence of a functional dipeptide transporter in isolated cardiomyocytes, with accompanying expression of PEPT2.

Animals↗
PubMed2002

The fecal microflora of 1-3-month-old infants during treatment with eight oral antibiotics.

We examined the fecal microflora of 1-3-month-old infants during treatment with phenoxymethylpenicillin, amoxycillin, pivampicillin, cefaclor, cefadroxil, loracarbef, erythromycin or cotrimoxazole. Escherichia coli increased during treatment with penicillins or cephalosporins, but was not affected by erythromycin or cotrimoxazole. Other enterobacteria were acquired or increased during treatment with all agents except cotrimoxazole. Enterococci persisted or increased during phenoxymethylpenicillin, cephalosporin or cotrimoxazole treatment, whereas erythromycin and the other penicillins suppressed them. Bacteroides, bifidobacteria and lactobacilli were suppressed to undetectable levels in most infants during treatment with all agents, except phenoxymethylpenicillin and loracarbef.

Bacterial Infections↗
PubMed1992

Cefaclor uptake by the proton-dependent dipeptide transport carrier of human intestinal Caco-2 cells and comparison to cephalexin uptake.

The human Caco-2 cell line spontaneously differentiates in culture to epithelial cells possessing intestinal enterocytic-like properties. These cells possess a proton-dependent dipeptide transport carrier that mediates the uptake of the cephalosporin antibiotic cephalexin (Dantzig, A.H. and Bergin, L. (1990) Biochim. Biophys. Acta 1027, 211-217). In the present study, the uptake of cefaclor was examined and found to be sodium-independent, proton-dependent, and energy-dependent. The initial rate of D-[3-phenyl-3H]cefaclor uptake was measured over a wide concentration range; uptake was mediated by a single saturable transport carrier with a Km of 7.6 mM and a Vmax of 7.6 nmol/min per mg protein and by a non-saturable component. Uptake was inhibited by dipeptides but not amino acids. The carrier showed a preference for the L-isomer. The effect of the presence of a 5-fold excess of other beta-lactam antibiotics was examined on the initial rates of 1 mM cefaclor and 1 mM cephalexin uptake. Uptake rates were inhibited by the orally absorbed antibiotics, cefadroxil, cefaclor, loracarbef, and cephradine and less so by the parenteral agents tested. The initial uptake rates of both D-[9-14C]cephalexin and D-[3-phenyl-3H]cefaclor were competitively inhibited by cephalexin, cefaclor, and loracarbef with Ki values of 9.2-13.2, 10.7-6.2, and 7.7-6.4 mM, respectively. Taken together, these data suggest that a single proton-dependent dipeptide transport carrier mediates the uptake of these orally absorbed antibiotics into Caco-2 cells, and provide further support for the use of Caco-2 cells as a cellular model for the study of the intestinal proton-dependent dipeptide transporter.

2,4-Dinitrophenol↗
PubMed1996

Characterisation of penicillin-G uptake in rabbit small-intestinal brush-border membrane vesicles.

Uptake of penicillin-G has been studied in rabbit intestinal brush-border membrane vesicles (BBMV). Penicillin-G was transported into the lumen of BBMV via an H+-dependent, Na+-independent uptake system. This was a saturable carrier-mediated process, which adhered to Michaelis-Menten kinetics, having a pH optimum of 4.5 and resulting in a net-negative charge transfer. Vmax was 59 nmol penicillin-G (mg protein)-1 (30s)-1 and Km 22.7 mM. Ampicillin, penicillin-V, cefadroxil, cephalexin, cephalothin, cephradine, L-carnosine, glycyl-L-alanine, glycyl-L-tyrosine and glycylglycylglycine inhibited the uptake of penicillin-G. However, glycylsarcosine stimulated uptake by 92%. Countertransport experiments suggested that this effect took place at the active site of the transporter. Penicillin-G uptake appeared to be mediated via a common transport system shared by penicillins, cephalosporins and peptides.

Amino Acid Sequence↗
PubMed1987

Binding of amino beta-lactam antibiotics to soluble protein from rat intestinal mucosa--I. Purification of drug-binding protein.

Several amino beta-lactam antibiotics, including ampicillin, amoxicillin, cyclacillin, cephalexin, cephradine and cefadroxil, were found to bind in vitro to specific components in 105,000 g supernatant of homogenate obtained from rat intestinal mucosa. The major binding component (fraction b) was purified by chromatography on DEAE-cellulofine and by gel filtration on Sephadex G-50. The molecular weight of fraction b was determined by SDS polyacrylamide gel electrophoresis (15,000 Da). The binding behaviour of these amino beta-lactam antibiotics to fraction b were estimated by equilibrium dialysis. There were significant high affinities of all tested amino beta-lactam antibiotics which were well absorbed from intestine, but there was not a good correlation between binding and absorption of these drugs. It was also found that poorly absorbed cephalosporins which lack aminobenzyl group in their structure, cefazolin and cephaloridine, did not bind to fraction b.

Animals↗
PubMedDate not supplied

Ceftibuten and bactericidal kinetics. Comparative in vitro activity against Enterobacteriaceae producing extended spectrum beta-lactamases.

Ceftibuten, compared to cefixime, cefetamet, cefpodoxime, loracarbef, cefprozil, cefuroxime, cefaclor, and cefadroxil, was the most active oral cephalosporin derivative against Enterobacteriaceae producing plasmid-encoded broad spectrum beta-lactamases. In a pharmacodynamic model, ceftibuten was bactericidal for Haemophilus influenzae and Streptococcus pneumoniae at concentrations simulating human serum levels following 200 mg, p.o., b.i.d.

Administration, Oral↗
PubMedDate not supplied

In vitro activity of cefpodoxime compared with other oral cephalosporins tested against 5556 recent clinical isolates from five medical centers.

A multicenter study was conducted in which the in vitro activity of cefpodoxime (the active metabolite of the prodrug ester cefpodoxime proxetil) was compared with those of cefixime, cefuroxime, cefaclor, cefadroxil, and clarithromycin against 5556 recent clinical isolates. Cefpodoxime demonstrated potent activity against members of the Enterobacteriaceae, in particular against species generally resistant to the established oral cephalosporins such as Proteus vulgaris [minimum inhibitory concentration (MIC)50, 0.12 microgram/ml], Providencia rettgeri (MIC50, 0.015 microgram/ml), and Serratia marcescens (MIC50, 2 micrograms/ml). Cefpodoxime was very effective against the fastidious organisms most frequently associated with respiratory infections, such as Streptococcus pneumoniae (MIC90, 0.12 microgram/ml), Haemophilus influenzae (MIC90, 0.12 microgram/ml), and Moraxella catarrhalis (MIC90, 1 microgram/ml). In contrast to other orally administrated third-generation cephalosporins (cefixime or ceftibuten), cefpodoxime demonstrated reasonable activity against oxacillin-susceptible staphylococci, with MIC50 ranging from 1 to 2 micrograms/ml. All cephalosporins tested demonstrated poor activity against Pseudomonas spp., Xanthomonas spp., Enterococcus spp., and oxacillin-resistant staphylococci. Cefpodoxime had the widest spectrum of activity of all tested oral cephalosporins.

Administration, Oral↗
PubMedDate not supplied

Experience with a drug formulary in a large Italian city hospital.

The preparation and distribution of a drug formulary, providing some 377 pharmacological entities together with significant general information, in a large city hospital, enabled the collection of data on the pattern of drug use in this setting. Out of the 377 selected drugs, 27 were never used in the course of one year: most notable among these were the cephalosporin cephalothin, the antifungal griseofulvin, piperazine and the leading anti-H1-blocker terfenadine. Thirteen pharmaceutical preparations were used in over 50,000 doses; among these were the amiloride + hydrochlorothiazide combination, co-trimoxazole and lorazepam. Examination of specific drug series, e.g. of cephalosporins, showed a clear preference for the longer acting ceftriaxone versus a minor use for oral agents, e.g. cefadroxil. There was a wide choice of cardiovascular agents and a relative stability in the preference for major and minor antipsychotics. Outside of the formulary list, only a small number of preparations were requested, among these some traditional analgesic combinations and some extractive products. The provision of a hospital formulary may, in some way, modify drug choice in the hospital, although some established patterns of use are difficult to change. On the other hand, some interesting information was provided on the criteria of choice of hospital physicians.

Formularies, Hospital as Topic↗
PubMed2005

Interaction of 31 beta-lactam antibiotics with the H+/peptide symporter PEPT2: analysis of affinity constants and comparison with PEPT1.

The activity of the renal peptide transporters PEPT2 and PEPT1 determines-among other factors such as metabolic stability in liver and plasma-the circulatory half-life of penicillins and cephalosporins during therapy. This study was initiated to examine systematically the interaction of beta-lactam antibiotics with PEPT2. Interaction of 31 cephalosporins and penicillins with the carrier protein was characterized by measuring their ability to inhibit the uptake of [(14)C]Gly-Sar into renal SKPT cells. Cefadroxil, cefaclor, cyclacillin, cephradine, cephalexin and moxalactam were recognized by PEPT2 with very high affinity comparable to that of natural dipeptides (K(i)=3-100microM). Ceftibuten, dicloxacillin, amoxicillin, metampicillin, cloxacillin, ampicillin, cefixime, cefamandole, oxacillin and cefmetazole interacted with PEPT2 with medium affinity (K(i)=0.1-5mM). For the other beta-lactam antibiotics studied interaction was very low or not measurable (K(i)>5mM). The affinity constants of beta-lactam antibiotics at rPEPT2 and hPEPT1 are significantly correlated, but the rank orders are not identical. Decisive differences between PEPT1 and PEPT2 recognition of the N-terminal part of the compounds became evident. Moreover, this large data set of affinity constants of beta-lactam antibiotics will be useful for structure-transport (binding) analyses of PEPT2.

Animals↗
PubMed2005

Bactericidal activity of oral beta-lactam antibiotics in plasma and urine versus isogenic Escherichia coli strains producing broad- and extended-spectrum beta-lactamases.

Bacteria harbouring extended-spectrum beta-lactamases (ESBLs), derived by mutation from TEM-1, TEM-2 or SHV-1 beta-lactamases, have been described world-wide. The in vitro activities of these enzymes against beta-lactam antibiotics, including oral cephalosporins, are well recognised. The aim of this investigation was to assess the bactericidal activity of oral beta-lactam antibiotics available in Croatia (amoxicillin/clavulanate, cephalexin, cefuroxime, cefadroxil and ceftibuten), in biological fluids against isogenic Escherichia coli strains producing broad-spectrum (TEM-1, TEM-2 and SHV-1) and extended-spectrum beta-lactamases (SHV-2, SHV-3, SHV-4, SHV-5, SHV-12). Bactericidal activity of oral beta-lactams in plasma and urine was tested in time-kill experiments and by determining bactericidal titres at different time intervals post-dose. The killing rate of antibiotics in urine was slower than in plasma, but faster than in Mueller-Hinton broth. High bactericidal titres in urine were only maintained throughout the whole dosing interval by ceftibuten against strains producing broad-, SHV-2 and SHV-3 beta-lactamases. The older generation cephalosporins can be considered for the therapy of urinary tract infections caused by E. coli harbouring TEM-1, TEM-2 and SHV-1 beta-lactamases but a shorter dosing interval is needed. Ceftibuten can be recommended with caution in ESBL producing E. coli except those producing SHV-4, SHV-5 and SHV-12 that confer resistance to it. If these enzymes are produced, fluoroquinolones or carbapenems could be considered.

Adult↗