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PubMed1992

[Bacteriostatic activity and killing curves of eight antibiotics against seven strains of penicillin G-resistant pneumococci].

Increasing resistance to multiple antimicrobial agents including penicillins is a current problem with Streptococcus pneumoniae. Seven cases of severe infection due to penicillin G-resistant pneumococci were seen in two teaching hospitals in Paris (France) during the first half of 1991; six of the strains were recovered from pulmonary secretions (protected brush specimens) and one from cerebrospinal fluid (CSF). The bacteriostatic activity and killing curves of eight antimicrobials against these seven strains were studied. Antimicrobial agents tested included penicillin G (PEN), amoxicillin (AMX), cefotaxime (CTX), imipenem (IPM), rifampin (RIF), vancomycin (VAN), fosfomycin (FOS), and erythromycin (ERO). MICs were determined using the agar dilution method. Killing curves were obtained using a liquid medium inoculated with 10(5) to 10(6) CFU/ml and subjected to continuous agitation; survivors were counted at baseline and after 1, 3 and 5 hours incubation. MICs of each antimicrobial (mg/l) for the seven strains were in the following ranges: PEN: 0.5-2, AMX: 0.5-2; CTX: 0.125-1; IPM: 0.03-0.25; RIF: 0.12-0.25; VAN: 0.25-1; FOS: 16; ERO: 0.06 greater than 4. Overall, bactericidal activity was greatest with vancomycin, followed by imipenem, then amoxicillin. The cefotaxime-fosfomycin combination proved synergistic and exhibited bactericidal activity (2MIC + 2MIC) for three of the seven strains. This study demonstrated the value of the cefotaxime-fosfomycin combination. Both these antimicrobials seem appropriate for the treatment of meningitis caused by penicillin G-resistant pneumococci provided their dosage is adjusted to achieve adequate drug levels in the cerebrospinal fluid.

Amoxicillin↗
PubMed1989

[Infections of the cerebrospinal fluid shunt].

The treatment of infectious complications of implanted foreign bodies into the CNS is unsatisfactory. In the majority of these patients staphylococci are responsible for these infections which elicit only a smoldering inflammatory response with poor penetration of antibiotics into the CSF. It is also very difficult to eradicate staphylococci from the surface of silastic material by antibiotics. Fosfomycin was investigated in the treatment of CSF infections in patients with infected ventriculoatrial shunts. Fosfomycin exhibits a potent antimicrobial activity against staphylococci; this drug also showed a favourable penetration into the CSF in moderately inflamed meninges. A 10 days therapeutic course with fosfomycin plus oxacillin or cefamandole and gentamycin in combination with external drainage of the CSF into a closed system made it possible to exchange all parts of the system in one session without reinfection. This procedure was followed by the same antibiotic regimen postoperatively for 10-14 days. Under this treatment schedule therapeutic results have been considerably better compared to previous treatment modalities.

Cerebrospinal Fluid Shunts↗
PubMed1989

Effects of antibiotic combinations on methicillin-resistant Staphylococcus aureus in vitro.

Methicillin-resistant Staphylococcus aureus (MRSA) infection has become an important infectious disease problem. Vancomycin is the only antimicrobial agent documented to be effective in the treatment of MRSA infection. Under vancomycin treatment there is still a moderate percentage of treatment failures, especially in severe MRSA infections. In searching for better treatment regimens, we evaluated the effects of several antibiotics in combination with vancomycin or fosfomycin against MRSA isolates by the checkerboard titration method. We found that the combinations of vancomycin with imipenem and fosfomycin with cefazolin had a synergistic effect against 97.1% and 94.3% of 70 tested strains, respectively. Rifampicin, gentamicin, cefazolin, or cefamandole in combination with vancomycin, and cefmetazole in combination with fosfomycin did not have such good results. They were synergistic against far fewer of the tested strains, 0%, 3.3%, 50.0%, 30.0% and 64.3%, respectively. For confirmation, further studies in vivo of the effectiveness are advisable. It is likely that we can improve the treatment of severe MRSA infections by those combination regimens which are highly synergistic against MRSA.

Drug Therapy, Combination↗
PubMed1997

[The drug sensitivity of enterohemorragic Escherichia coli and antibiotics treatment for hemorrhagic enterocolitis--from an outbreak of enterocolitis in Sakai city].

In July, 1996, a massive outbreak of hemorrhagic enterocolitis involving more than 5,000 people was caused by enterohemorragic Escherichia coli (EHEC) O157:H7 occurred mainly among elementary school children of Sakai City, Japan. The antibacterial activities in vitro against EHEC from stool specimens were determined. Norfloxacin showed the highest antibacterial activity, and fosfomycin, kanamycin, ampicillin, cefaclor were considered as effective drugs. But doxycycline showed lower antibacterial activities compared to other examined drugs, and it appears necessary to take antibiotic resistance of Escherichia coli into consideration when a treatment regimen is determined. As a result of the oral administration of fosfomycin to 95 patients of hemorrhagic enterocolitis and carrier, no patients developed complications with hemolytic uremic syndrome (HUS). However, a study of 17 patients with HUS demonstrated the fact that most of them were subjected to intravenous administration of fosfomycin. It may be needed to consider oral administration route of effective antibiotics in the treatment of enterocolitis in order to maintain high concentrations of a drug in the intestine.

Administration, Oral↗
PubMed1996

Study of Pseudomonas aeruginosa serotype O12 isolates with a common antibiotic susceptibility pattern.

A multicentre European study of Pseudomonas aeruginosa serotype O12 isolates with a common antibiotic resistance pattern was conducted. Resistance to beta-lactams and aminoglycosides was observed in 24 of the 25 isolates, as often reported in Europe, and all 25 isolates were significantly more susceptible to fosfomycin than 189 isolates of other serotypes (72% vs. 13.2%). The mutational frequency of serotype O12 was similar to that of other serotypes and thus could not explain the susceptibility to fosfomycin. As a number of epidemiological studies using various methods, especially ribotyping with EcoRI, have shown that most strains are similar, it has been suggested that a single strain of this serotype is widespread. However, in this study ribotyping with EcoRI and PvuII distinguished seven clones among 24 ticarcillin resistant serotype O12 isolates, although one ribotype predominated (67%). Thus the hypothesis of spread of one clone across Europe cannot explain the common resistance phenotype observed in different clones of serotype O12. Resistance of beta-lactams and aminoglycosides might be explained by greater receptiveness for transposable resistance mechanisms, and susceptibility to fosfomycin by increased permeability of the outer membrane.

Anti-Bacterial Agents↗
PubMed2005

Natural antimicrobial susceptibility patterns and biochemical identification of Escherichia albertii and Hafnia alvei strains.

Bangladeshi diarrheagenic Hafnia alvei-like strains have been described recently as the new species Escherichia albertii (Int J Syst Evolut Microbiol. 2003;53:807-810). The natural susceptibility of 21 E. albertii and 76 H. alvei strains to 69 antimicrobial agents was examined, applying a microdilution procedure in IsoSensitest broth (for all the strains) and cation-adjusted Mueller-Hinton broth (for some strains). Examining the phenotypic features of both taxa with commercial identification systems and conventional tests, a database for an accurate biochemical separation of E. albertii from H. alvei was also established. Both taxa were naturally sensitive or sensitive and of intermediate susceptibility to aminoglycosides, acylureidopenicillins, ticarcillin, several cephalosporins, carbapenems, aztreonam, quinolones, folate pathway inhibitors, and nitrofurantoin. They were naturally resistant to tetracycline, penicillin G, oxacillin, all macrolides except for azithromycin, lincosamides, streptogramins, glycopeptides, rifampicin, and fusidic acid. Taxon-related differences in natural susceptibility affecting clinical assessment criteria were seen with doxycycline, minocycline, aminopenicillins, some cephalosporins, azithromycin, and fosfomycin. E. albertii was more susceptible than H. alvei to these agents and was naturally sensitive to all beta-lactams (except for penicillin G and oxacillin), azithromycin, and fosfomycin. H. alvei was naturally resistant or of intermediate susceptibility to all tetracyclines, amoxicillin, amoxicillin-clavulanate, ampicillin-sulbactam, narrow-spectrum cephalosporins, azithromycin, and fosfomycin. Motile malonate-negative Hafnia strains (indicating genospecies 2 of the H. alvei complex) were less susceptible to some cephalosporins than nonmotile, malonate-positive hafniae (indicating genospecies 1). Proline deaminase, hydroxyproline amidase, tripeptidase, chitinase, Voges-Proskauer reaction, and assimilation of histidine as well as acid production from glycerol, rhamnose, and xylose were suitable tests to separate strains of E. albertii from those of the H. alvei complex. Although out of the scope of this study, it should be noted that several strains of E. albertii showed acquired resistances to some penicillins and antifolates.

Anti-Bacterial Agents↗
PubMed2000

Natural antibiotic susceptibility of Salmonella enterica strains.

The susceptibility of 100 Salmonella enterica strains belonging to S. enterica subsp. enterica (n=90) and S. enterica subsp. arizonae (n=10) was examined to 71 antibiotics. Within S. enterica subsp. enterica, strains of different serovars (typhimurium (n=17), enteritidis (n=17), dublin (n=10), typhi (n=16), paratyphi A (n=6), others (n=24)) were studied. MICs were determined using a microdilution procedure and apart from fosfomycin there were no significant differences in susceptibility between the subspecies and serovars of S. enterica. All salmonellae were sensitive or intermediately resistant to tetracyclines, aminoglycosides, most beta-lactam antibiotics, quinolones, co-trimoxazole group antibiotics, chloramphenicol, nitrofurantoin and azithromycin. S. enterica strains were intrinsically resistant to benzylpenicillin, oxacillin, most macrolides, rifampicin, lincosamides, streptogramins, glycopeptides and fusidic acid. Apart from some slight differences in antibiotic susceptibility between strains of S. enterica subsp. enterica and S. enterica subsp. arizonae, only the susceptibility to fosfomycin varied among the taxa studied. Whereas 'enteric' salmonellae including S. enterica subsp. arizonae were sensitive to fosfomycin, 'typhoid' salmonellae were intrinsically resistant. A database of the antibiotic susceptibility of S. enterica was set up. It may be of use to validate antibiotic susceptibility test results of these bacteria.

Anti-Bacterial Agents↗
PubMed1998

Studies on the conformational changes in the bacterial cell wall biosynthetic enzyme UDP-N-acetylglucosamine enolpyruvyltransferase (MurA).

The enzyme UDP-N-acetylglucosamine (UDP-GlcNAc) enolpyruvyltransferase (MurA), the target of the antibiotic fosfomycin, was investigated by small-angle X-ray scattering (SAXS) and fluorescence spectroscopy to detect conformational changes that had been proposed on the basis of the crystal structure of unliganded and liganded MurA. The SAXS data indicate that binding of UDP-GlcNAc to free enzyme results in substantial conformational changes, which can be interpreted as the transition from an open to a closed form. Fosfomycin did not affect the structure of free enzyme or sugar-nucleotide-bound MurA. Phosphoenolpyruvate (pyruvate-P) appeared to induce a structural change upon addition to free enzyme, which differed from that observed upon binding of UDP-GlcNAc. Fluorescence experiments were performed using the hydrophobic fluorescence probe 8-anilino-1-naphthalene sulfonate (ANS). The fluorescence quenching of MurA/ANS solutions upon addition of UDP-GlcNAc or pyruvate-P was concentration dependent in a saturating manner, yielding apparent dissociation constants of K(d(UDP-GlCNAc)) = 59 microM and K(d(pyruvate-P)) = 240 microM. The results suggest that binding of substrates does not exclusively follow an ordered mechanism with UDP-GlcNAc binding first, although binding of UDP-GlcNAc to free enzyme is preferred and possibly influenced by pyruvate-P. The reaction thus appears to follow an induced-fit mechanism, in which the binding site for fosfomycin, and presumably also for pyruvate-P, is created by the interaction of free enzyme with the sugar nucleotide. The methods described here provide a tool for the characterization of site-directed mutants of MurA and the interaction of this enzyme with potential inhibitors.

Alkyl and Aryl Transferases↗
PubMed2003

An international survey of the antimicrobial susceptibility of pathogens from uncomplicated urinary tract infections: the ECO.SENS Project.

The ECO.SENS study is the first international survey to investigate the prevalence and susceptibility of pathogens causing community-acquired acute uncomplicated urinary tract infections (UTIs). Midstream urine samples were taken for culture and for testing for the presence of leucocytes from 4734 women not older than 65 years presenting with symptoms of acute UTI at 252 community health care centres in 17 countries. Recognized urinary tract pathogens were identified and the susceptibility to 12 antimicrobials determined. Pathogens were present in 3278 (69.2%) patients, Escherichia coli accounting for 77.0% of isolates. In E. coli, 42% of the isolates were resistant to one or more of the 12 antimicrobial drugs investigated. Resistance was most common to ampicillin (29.8%) and sulfamethoxazole (29.1%), followed by trimethoprim (14.8%), trimethoprim/sulfamethoxazole (14.1%) and nalidixic acid (5.4%). Resistance in E. coli to co-amoxiclav, mecillinam, cefadroxil, nitrofurantoin, fosfomycin, gentamicin and ciprofloxacin was <3%. However, co-amoxiclav resistance was apparent in Portugal (9.3%) as was resistance to the quinolones, nalidixic acid and ciprofloxacin, in Portugal (11.6% and 5.8%, respectively) and Spain (26.7% and 14.7%, respectively). Overall, Proteus mirabilis were less resistant to ampicillin (16.1%) and more resistant to trimethoprim (25.5%) than E. coli, whereas Klebsiella spp. were more resistant to ampicillin (83.5%) and fosfomycin (56.7%). 'Other Enterobacteriaceae' were more resistant to the broad spectrum beta-lactams (ampicillin 45.9%, co-amoxiclav 21.3% and cefadroxil 24.6%), nitrofurantoin (40.2%) and fosfomycin (15.6%). In Staphylococcus saprophyticus resistance development was rare. Overall, antimicrobial resistance was lowest in the Nordic countries and Austria and highest in Portugal and Spain.

Adolescent↗
PubMed1998

Natural antibiotic susceptibility of Providencia stuartii, P. rettgeri, P. alcalifaciens and P. rustigianii strains.

The natural antibiotic susceptibility of 38 Providencia rettgeri, 35 P. stuartii, 23 P. alcalifaciens and 20 P. rustigianii strains was examined. MIC values were determined by a microdilution procedure and evaluated by a table calculation programme. P. stuartii was the least susceptible Providencia sp. and was naturally resistant to tetracyclines, some penicillins, older cephalosporins, sulphamethoxazole and fosfomycin and to antibiotics to which other species of Enterobacteriaceae are also resistant. It was naturally sensitive to modern penicillins and cephalosporins, carbapenems and aztreonam, but its susceptibility to aminoglycosides and quinolones was difficult to assess. P. alcalifaciens and P. rustigianii strains were the most susceptible Providencia spp. They were naturally sensitive or intermediate to tetracyclines and sensitive to aminoglycosides and quinolones. Susceptibility to sparfloxacin, biapenem and sulphamethoxazole permitted the discrimination of P. alcalifaciens and P. rustigianii strains. The natural antibiotic susceptibility of P. rettgeri strains was between that of P. stuartii and that of the other providenciae. P. rettgeri was resistant to tetracyclines and fosfomycin, but more susceptible to aminoglycosides, quinolones, fosfomycin and numerous beta-lactam antibiotics than P. stuartii. A database is described of the natural antibiotic susceptibilities of Providencia spp. It can be used for the validation of antibiotic susceptibility test results of these micro-organisms.

Anti-Bacterial Agents↗
PubMedDate not supplied

Surveillance of Pseudomonas aeruginosa in intensive care units: clusters of nosocomial cross-infection and encounter of a multiple-antibiotic resistant strain.

Serogrouping (determination of O antigens) and bacteriocin typing (based on susceptibility to one or more of 18 bacteriocins) were employed to survey 210 isolates of Pseudomonas aeruginosa from 201 patients in 8 intensive care units (ICU) during an observation period of 18 months. Eighty-eight isolates (41.9%) were nonserogroupable (NT); most common were serogroups O1, O9, O11, and O3. All except 5 isolates (97.6%) were bacteriocin-typable. However, phenotypic variation of bacteriocin susceptibility, in particular the receptor for bacteriocin No. 13, rendered this typing method presumptive as well. Bacteriocin susceptibility profiles were not predictive of serogroup and vice versa. Workup of 19 isolates from 9 patients disclosed phenotypic variation of antibiotic susceptibility in 3 patients, superinfection by a different strain in 4 patients, and persistence (3 months) of the same strain in 2 patients, respectively. Serotyping and bacteriocin susceptibility test data revealed 15 clusters of putative cross-infection of 2 patients each, 8 clusters involving 3 patients each, one outbreak (serogroup NT, bacteriocin profile 777736) involving 4 patients in the pediatric ICU, one outbreak due to a multiple-antibiotic resistant (MAR) strain in the surgical ICU (4 patients, serogroup O12, bacteriocin profile 30400), and two putative outbreaks in the pneumonology ICU involving 6 patients (serogroup NT, bacteriocin profile 777726) and 9 patients (serogroup NT, bacteriocin profile 777736). Pulsed-field gel electrophoresis (PFGE) macrorestriction analysis (SpeI, XbaI) confirmed the pediatric and surgical ICU strains as singular strains. However, the two putative outbreaks in the pneumonology ICU were due to one particular strain which had infected 13 of the 15 patients as determined with the PFGE genotypic method. Isolates comprising the MAR strain of P. aeruginosa were susceptible only to amikacin, fosfomycin, and polymyxin B; the isolates varied in susceptibility to aztreonam and ceftazidime. This MAR strain was susceptible to the bactericidal activity of 65 vol% of fresh defibrinated human blood from donors B, L, and T. Either amikacin (16 micrograms/ ml) or fosfomycin (8 micrograms/ml) plus blood and amikacin (8 micrograms/ml) combined with fosfomycin (8 micrograms/ml) with and without blood consistently killed isolates of the MAR strain, which thus was amenable to antibiotic therapy.

Anti-Bacterial Agents↗
PubMed1998

[Status of emerging drug resistance in Shiga toxin-producing Escherichia coli in Japan during 1996: a minireview].

A total of 192 Shiga toxin-producing Escherichia coli (STEC) strains isolated from the 1996 episodes in Japan were tested for their in vitro susceptibilities to 41 antimicrobial agents. Drug resistance was found with kanamycin, tetracycline, nalidixic acid, ampicillin, streptomycin, sulfamethoxazole, and fosfomycin. The expression of fosfomycin resistance was greatly dependent on culture conditions and resistance was detected (e.g.) when Mueller-Hinton agar or nutrient agar supplemented with horse blood (or glucose-6-phosphate) was used as test media. All the STEC strains belonging to serotype O26 exhibited fosfomycin resistance. Multiple drug-resistant strains spread 8 of 18 prefectures examined. Out of eleven O157: H7 outbreaks, only one outbreak revealed infections due to multiple drug-resistant strains which carried an R plasmid. Tetracycline, streptomycin, and sulfamethoxazole resistance, which was previously described with O157: H7 strains isolated from a large outbreak as well as sporadic cases in the United States, were also found in Japan with human and bovine isolates (but not with porcine isolates). In contrast, the STEC strains were highly susceptible to newer quinolones, cephems, trimethoprim, gentamicin, and azithromycin. No drug resistance was observed with dibekacin and minocycline.

Animals↗
PubMed1995

Improved strains of recombinant Escherichia coli for ethanol production from sugar mixtures.

Hemicellulose hydrolysates of agricultural residues often contain mixtures of hexose and pentose sugars. Ethanologenic Escherichia coli that have been previously investigated preferentially ferment hexose sugars. In some cases, xylose fermentation was slow or incomplete. The purpose of this study was to develop improved ethanologenic E. coli strains for the fermentation of pentoses in sugar mixtures. Using fosfomycin as a selective agent, glucose-negative mutants of E. coli KO11 (containing chromosomally integrated genes encoding the ethanol pathway from Zymomonas mobilis) were isolated that were unable to ferment sugars transported by the phosphoenolpyruvate-dependent phosphotransferase system. These strains (SL31 and SL142) retained the ability to ferment sugars with independent transport systems such as arabinose and xylose and were used to ferment pentose sugars to ethanol selectively in the presence of high concentrations of glucose. Additional fosfomycin-resistant mutants were isolated that were superior to strain KO11 for ethanol production from hexose and pentose sugars. These hyperproductive strains (SL28 and SL40) retained the ability to metabolize all sugars tested, completed fermentations more rapidly, and achieved higher ethanol yields than the parent. Both SL28 and SL40 produced 60 gl-1 ethanol from 120 gl-1 xylose in 60 h, 20% more ethanol than KO11 under identical conditions. Further studies illustrated the feasibility of sequential fermentation. A mixture of hexose and pentose sugars was fermented with near theoretical yield by SL40 in the first step followed by a second fermentation in which yeast and glucose were added. Such a two-step approach can combine the attributes of ethanologenic E. coli for pentoses with the high ethanol tolerance of conventional yeasts in a single vessel.

Carbohydrate Metabolism↗
PubMed1999

Efficacy of antibiotic therapy for infection with Shiga-like toxin-producing Escherichia coli O157:H7 in mice with protein-calorie malnutrition.

Antibiotic therapy for infection with Shiga-toxin-producing Escherichia coli O157:H7 is controversial because of the possibility of its inducing hemolytic uremic syndrome and acute encephalopathy. In a previous study, mice with protein-calorie malnutrition were found to be highly susceptible to this pathogen. The efficacy of oral antibiotic therapy in malnourished mice infected with O157 organisms was assessed. Mice fed a low-protein calorie diet were infected intragastrically with 2 x 10(6) colony-forming units of a Shiga-toxin-producing strain of Escherichia coli O157:H7. Infected mice were orally given a therapeutic dose of an antibiotic, including norfloxacin, fosfomycin, kanamycin, ampicillin, clarithromycin or trimethoprim-sulfamethoxazole for 3 days: mice on protocol A received the antibiotic on days 1-3, starting on the day after infection, and mice on protocol B received the antibiotic on days 3-5. The duration of fecal pathogen excretion was shorter and the toxin level in the stool and blood lower in the mice that received protocol A than in untreated mice; all of the mice treated on protocol A survived the lethal infection. All antibiotics except trimethoprim-sulfamethoxazole, administered on protocol B, exhibited the same effect as that exhibited by the respective antibiotic administered on protocol A. Only the mice treated with protocol B of trimethoprim-sulfamethoxazole had a higher toxin level in the blood than untreated controls, resulting in 95% mortality. These results suggest that the antibiotics used in this study, except for trimethoprim-sulfamethoxazole, could reduce the risk of hemolytic uremic syndrome and acute encephalopathy following Escherichia coli O157:H7 infection in humans, and that fosfomycin, in particular, may be relevant for testing in humans.

Ampicillin↗
PubMed1986

In vitro interactions between teicoplanin and other antibiotics against enterococci and staphylococci.

In this study we have evaluated the in vitro activity of teicoplanin, a potent anti-staphylococcal and anti-enterococcal agent, in combination with rifampicin, netilmicin, amikacin, fosfomycin and imipenem. Drug interactions were assessed using a microtitre checkerboard dilution method and a time-kill test. With rifampicin, indifference or an additive effect was the prevalent outcome with both methods. With netilmicin and amikacin synergism was seen against half of the enterococcal strains, whereas indifference was more common with staphylococcal isolates. Synergism predominated when teicoplanin was combined with fosfomycin and imipenem. Under no circumstances and with no combination of drugs were we able to detect antagonistic effects.

Amikacin↗
PubMed2005

Site-directed mutagenesis and spectroscopic studies of the iron-binding site of (S)-2-hydroxypropylphosphonic acid epoxidase.

(S)-2-Hydroxylpropanylphosphonic acid epoxidase (HppE) is a novel type of mononuclear non-heme iron-dependent enzyme that catalyzes the O2 coupled, oxidative epoxide ring closure of HPP to form fosfomycin, which is a clinically useful antibiotic. Sequence alignment of the only two known HppE sequences led to the speculation that the conserved residues His138, Glu142, and His180 are the metal binding ligands of the Streptomyces wedmorensis enzyme. Substitution of these residues with alanine resulted in significant reduction of metal binding affinity, as indicated by EPR analysis of the enzyme-Fe(II)-substrate-nitrosyl complex and the spectral properties of the Cu(II)-reconstituted mutant proteins. The catalytic activities for both epoxidation and self-hydroxylation were also either eliminated or diminished in proportion to the iron content in these mutants. The complete loss of enzymatic activity for the E142A and H180A mutants in vivo and in vitro is consistent with the postulated roles of the altered residues in metal binding. The H138A mutant is also inactive in vivo, but in vitro it retains 27% of the active site iron and nearly 20% of the wild-type activity. Thus, it cannot be unequivocally stated whether H138 is an iron ligand or simply facilitates iron binding due to proximity. The results reported herein provide initial evidence implicating an unusual histidine/carboxylate iron ligation in HppE. By analogy with other well-characterized enzymes from the 2-His-1-carboxylate family, this type of iron core is consistent with a mechanism in which both oxygen and HPP bind to the iron as a first step in the in the conversion of HPP to fosfomycin.

Amino Acid Sequence↗
PubMed1997

Controlled release of antibiotics from biomedical polyurethanes: morphological and structural features.

Polymer-associated infections are of increasing importance. Antistaphylococcal antimicrobial substances (ciprofloxacin, gentamycin, fosfomycin, flucloxacillin) were incorporated into polyurethanes by the solvent casting technique. Drug release rates, bacterial colonization and morphological features were evaluated to predict and understand the antimicrobial activity of these delivery systems. Drug release characteristics were investigated by standard bioassay and high-performance liquid chromatography (HPLC), and the physico-chemical mechanisms of the delivery were discussed. Ciprofloxacin hydrochloride showed a fast initial release rate, whereas gentamicin-base was characterized by a more continuous release type of behaviour. Bacterial colonization to the antibiotic-loaded polyurethanes was inhibited effectively by preparations showing a slower but more sustained antimicrobial delivery. Polyurethane-antibiotic combinations were most homogeneous for gentamicin-base and flucloxacillin as shown by scanning electron microscopy (SEM). In polymers loaded with fosfomycin and ciprofloxacin a granular structure of the crystallized drug embedded in the polyurethane matrix could be demonstrated. Physico-chemical similarity of the polymeric material and the antibiotics is important for the homogeneity of polymer-antibiotic combinations. High homogeneity is required for a sustained and prolonged release over time and effective inhibition of bacterial colonization.

Anti-Bacterial Agents↗
PubMed2001

Campylobacter, Salmonella, Shigella and Escherichia coli in live and dressed poultry from metropolitan accra.

This study on the microbiology of chicken assessed a total of 97 live birds from three selected farms and 87 carcasses/chicken parts from two supermarkets, two open markets and one wholesale outlet (cold store) in the Accra metropolis. Campylobacter spp. were isolated from 14 (14.4%) gut contents of live birds from three farms. None of the frozen birds were positive for Campylobacter spp. These isolates were sensitive to most common antibiotics but not to ampicillin and tetracyclines. Salmonella spp. were isolated from 7 (7.2%) gut contents and 13 (6.8%) carcasses and were resistant to erythromycin. cefotiam, penicillin, ampicillin and cefadroxil. Samonella spp. had varied susceptibilities to nalidixic acid, chloramphenicol and minocyclin. No Shigella spp. was isolated from any of the live birds but 6 (6.9%) of imported chicken samples from the cold store and two markets were positive. Fosfomycin and chloramphenicol were the only antibiotics effective against these isolates. Twelve different Escherichia coli serovars were identified from the total of 21 positive samples. These, in order of magnitude isolated, are E. coli 0158 (14.3%), 0125 (14.3%), 025 (9.5%), 028ac (9.5%), 0159 (9.5%). 015 (9.5%), 0126 (9.5%), 063 (4.8%), 0143 (4.8%), 026 (4.8%), 078 (4.8%), 0164 (4.8%). Cefadroxil, ampicillin, penicillin, cefotiam, tetracycline and erythromycin were ineffective against all strains of E. coli isolated. Minocyclin was effective against all strains with the exception of E. coli 0159, 025, 0164 and 063, which were moderately susceptible. All strains with exception of E. coli 0164 were susceptible to fosfomycin. Nalidixic acid, chloramphenicol, kanamaycin, ceftrioxone and amoxycillin all showed varied effectiveness against the strains isolated. It is concluded that imported and locally produced chicken is a potential source of multiple-antibiotic-resistant enteropathogenic bacteria. Measures to improve the microbial quality of chicken are discussed.

Animals↗