Activity of fosfomycin against Pasteurella.
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Administration, Oral↗
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An in-vitro study of the antimicrobial susceptibilities of Yersinia enterocolitica and the definition of a database.
The antibiotic susceptibilities of 151 Yersinia enterocolitica strains isolated from humans, animals and the environment, and belonging to biovars 1A (n = 22), 1B (n = 13), 2 (n = 12), 3 (n = 31), 4 (n = 63) and 5 (n = 10) to 71 antibiotics were examined. Biovars could be characterized phenotypically by their similar antibiograms. For the majority of biovars only minor differences in susceptibilities were detected. Ninety-nine percent of all Yersinia strains were resistant to amoxycillin, but biovar-related differences in MICs were demonstrated. Significant differences, characteristic of specific biovars, were detected for fosfomycin, some beta-lactams (in particular amoxycillin/clavulanate, and ticarcillin). Strains of biovar 1A were resistant or of intermediate susceptibility to ticarcillin and had fosfomycin MICs of 16-64 mg/L and amoxycillin/clavulanate MICs of 4-32 mg/L. Most strains of biovar 1B (n = 11) were sensitive to amoxycillin/clavulanate (MIC = 0.5-2 mg/L). Most strains of biovar 2 (n = 10) showed an antibiotic phenotype resembling that of strains of biovar 1A, but they were more susceptible to fosfomycin (MIC = 4-16 mg/L). Twenty-seven strains of biovar 3 had amoxycillin/clavulanate MICs of 4-32 mg/L; 19 of them were sensitive to ticarcillin and fosfomycin. Biovar 4 strains were uniformly sensitive or of intermediate susceptibility to amoxycillin/clavulanate (MIC = 0.5-4 mg/L), sensitive to fosfomycin (MIC = 1-4 mg/L) but resistant to ticarcillin. The prevailing antibiotic phenotype of biovar 5 (n = 7) was similiar to the phenotype of biovar 4, although these biovar 5 strains were slightly more susceptible to amoxycillin/clavulanate and showed a heterogeneous pattern of susceptibility to fosfomycin (MIC = 1-32 mg/L). The results of this study show that unambiguous statements cannot be made about the natural antibiotic susceptibility to certain beta-lactams and fosfomycin of Y. enterocolitica. The data indicate a complex regulation of beta-lactamases in Y. enterocolitica. Some beta-lactamases are found more frequently or will be expressed predominantly in specific biovars.
Anti-Bacterial Agents↗
Single dose and conventional treatment for acute bacterial and non-bacterial dysuria and frequency in general practice.
A five day course of clavulanate-potentiated amoxicillin (Augmentin) has been compared with a single oral dose of fosfomycin trometamol in the treatment of patients complaining of symptoms suggesting urinary tract infection. The study took place in a single urban general practice of 15,000 patients in Cheshire. The microbiology was performed at a London Teaching Hospital. 141 patients entered the trial. 65 had a significant bacteriuria, 62 of which were assessable for the ability of the trial drugs to eradicate bacteriuria: 29 patients received clavulanate-potentiated amoxicillin and 33 fosfomycin trometamol. The cure rates, assessed at five to ten days and at four to six weeks post treatment, were 72% and 65%, respectively for clavulanate-potentiated amoxicillin and 85% and 81%, respectively for fosfomycin trometamol. Side effects, assessed in all 141 patients, occurred in 11.6% receiving clavulanate-potentiated amoxicillin and in 8.3% receiving fosfomycin. Statistically there is no difference between any of these findings and the effect of sample size is discussed. 69 patients were symptomatic but did not have a significant bacteriuria ("urethral syndrome"). These patients were assessed for the effect of treatment in relieving symptoms: 33 received fosfomycin trometamol and 36 clavulanate-potentiated amoxicillin. The success and speed of relieving the symptoms were very similar in the two groups. The finding that both groups responded equally well appears to refute an aetiological role for lactobacilli and diphtheroids in the "urethral syndrome", since these organisms are resistant to fosfomycin but sensitive to clavulanate-potentiated amoxicillin.
Adolescent↗
Thermodynamic characterization of ligand-induced conformational changes in UDP-N-acetylglucosamine enolpyruvyl transferase.
The binding of UDP-N-acetylglucosamine (UDPNAG) to the enzyme UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) was studied in the absence and presence of the antibiotic fosfomycin by isothermal titration calorimetry. Fosfomycin binds covalently to MurA in the presence of UDPNAG and also in its absence as demonstrated by MALDI mass spectrometry. The covalent attachment of fosfomycin affects the thermodynamic parameters of UDPNAG binding significantly: In the absence of fosfomycin the binding of UDPNAG is enthalpically driven (DeltaH = -35.5 kJ mol(-1) at 15 degrees C) and opposed by an unfavorable entropy change (DeltaS = -25 J mol(-1) K(-1)). In the presence of covalently attached fosfomycin the binding of UDPNAG is entropically driven (DeltaS = 187 J mol(-1)K(-1) at 15 degrees C) and associated with unfavorable changes in enthalpy (DeltaH = 28.8 kJ mol(-1)). Heat capacities for UDPNAG binding in the absence or presence of fosfomycin were -1.87 and -2.74 kJ mol(-1) K(-1), respectively, indicating that most ( approximately 70%) of the conformational changes take place upon formation of the UDPNAG-MurA binary complex. The major contribution to the heat capacity of ligand binding is thought to be due to changes in the solvent-accessible surface area. However, associated conformational changes, if any, also contribute to the experimentally measured magnitude of the heat capacity. The changes in solvent-accessible surface area were calculated from available 3D structures, yielding a DeltaC(p) of -1.3 kJ mol(-1) K(-1); i.e., the experimentally determined heat capacity exceeds the calculated one. This implies that other thermodynamic factors exert a large influence on the heat capacity of protein-ligand interactions.
Alkyl and Aryl Transferases↗
Biochemical and spectroscopic studies on (S)-2-hydroxypropylphosphonic acid epoxidase: a novel mononuclear non-heme iron enzyme.
The last step of the biosynthesis of fosfomycin, a clinically useful antibiotic, is the conversion of (S)-2-hydroxypropylphosphonic acid (HPP) to fosfomycin. Since the ring oxygen in fosfomycin has been shown in earlier feeding experiments to be derived from the hydroxyl group of HPP, this oxirane formation reaction is effectively a dehydrogenation process. To study this unique C-O bond formation step, we have overexpressed and purified the desired HPP epoxidase. Results reported herein provided initial biochemical evidence revealing that HPP epoxidase is an iron-dependent enzyme and that both NAD(P)H and a flavin or flavoprotein reductase are required for its activity. The 2 K EPR spectrum of oxidized iron-reconstituted fosfomycin epoxidase reveals resonances typical of S = (5)/(2) Fe(III) centers in at least two environments. Addition of HPP causes a redistribution with the appearance of at least two additional species, showing that the iron environment is perturbed. Exposure of this sample to NO elicits no changes, showing that the iron is nearly all in the Fe(III) state. However, addition of NO to the Fe(II) reconstituted enzyme that has not been exposed to O(2) yields an intense EPR spectrum typical of an S = (3)/(2) Fe(II)-NO complex. This complex is also heterogeneous, but addition of substrate converts it to a single, homogeneous S = (3)/(2) species with a new EPR spectrum, suggesting that substrate binds to or near the iron, thereby organizing the center. The fact that NO binds to the ferrous center suggests O(2) can also bind at this site as part of the catalytic cycle. Using purified epoxidase and (18)O isotopic labeled HPP, the retention of the hydroxyl oxygen of HPP in fosfomycin was demonstrated. While ether ring formation as a result of dehydrogenation of a secondary alcohol has precedence in the literature, these catalyses require alpha-ketoglutarate for activity. In contrast, HPP epoxidase is alpha-ketoglutarate independent. Thus, the cyclization of HPP to fosfomycin clearly represents an intriguing conversion beyond the scope entailed by common biological epoxidation and C-O bond formation.
Amino Acid Sequence↗
Cefotaxime in combination with other antibiotics for the treatment of severe methicillin-resistant staphylococcal infections.
Methicillin-resistant staphylococci (M-R staphylococci) represent 30% of the staphylococcal strains isolated in our hospital and pose important therapeutic problems. In a preliminary in vitro checkerboard study the bactericidal effect of various cephalosporins (cephalothin, cefamandole, cefotaxime and cefoperazone) in combination with other antibiotics (netilmicin, amikacin, vancomycin and fosfomycin) was studied on ten M-R staphylococcal strains. The combinations of cefoperazone with amikacin, cephalothin with vancomycin and of the four cephalosporins with fosfomycin were synergistic on the ten strains (FBC indexes less than or equal to 0.75). According to the CSF and bone levels achieved by these antibiotics and their bactericidal concentrations in combination, the combination of cefotaxime and fosfomycin was the most interesting, a concentration of less than or equal to 2 mg/l cefotaxime being bactericidal on five homogeneous M-R Staphylococcus aureus when combined with 4 mg/l of fosfomycin. This combination of cefotaxime (25 mg/kg, i.v. infusion over 30 min) and fosfomycin (50 mg/kg, i.v. infusion over three hours) three to four times daily was used to treat 16 patients: three patients with meningitis, six with bone and joint infections and seven with persistent bacteremia. The FBC indexes were less than or equal to 0.625 for the 12 strains studied. All the patients were cured without relapses. The concentrations of cefotaxime, desacetyl cefotaxime and fosfomycin in the CSF during meningitis three hours after the end of the infusion on the second day of treatment were 8.76, 6.82 and 58.0 mg/l, respectively, for patient one and 2.0, 0.53 and 31.0 mg/l, respectively, for patient two.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
In vitro and in vivo antibacterial activity of FR-31564, a phosphonic acid antimicrobial agent.
The in vitro and in vivo activity of FR-31564 [sodium hydrogen 3-(N-hydroxyformamido)propylphosphate] against gram-positive and -negative aerobic and anaerobic bacteria was investigated and compared with that of fosfomycin, cephalexin, carbenicillin, and trimethoprim-sulfamethoxazole. The in vitro activity of FR-31564 was markedly enhanced when combined with glucose 6-phosphate or fructose 6-phosphate, but not when combined with ribose phosphate, adenosine monophosphate, or glycerol phosphate. In vitro activity of FR-31564 also was enhanced by human or horse blood, but not by human serum. The type of medium had a great effect on the minimal inhibitory concentration, with the lowest minimal inhibitory concentrations achieved on nutrient agar, 8- to 16-fold less than with Mueller-Hinton, heart infusion, or Trypticase soy agars. FR-31564 was more active than fosfomycin, cephalexin, carbenicillin, or trimethoprimsulfamethoxazole against Escherichia coli, Klebsiella pneumoniae, Proteus vulgaris, Enterobacter cloacae, E. aerogenes, and Citrobacter. It was less active than fosfomycin against Serratia marcescens and Proteus mirabilis and did not inhibit gram-positive cocci or anaerobic species. FR-31564 inhibited a number of E. coli, K. pneumoniae, and some Pseudomonas aeruginosa strains resistant to the other agents. In the presence and absence of human blood FR-31564 showed bactericidal activity, and P. aeruginosa exposed to FR-31564 for 3 h showed a 6-h lag in regrowth. FR-31564 administered by the subcutaneous route was more active in protecting mice challenged with P. aeruginosa than was fosfomycin, carbenicillin, or cefoperazone. It was as active by the oral route in protecting mice challenged with E. coli as was fosfomycin, ampicillin, cephalexin, or trimethoprimsulfamethoxazole.
Animals↗
Identification and characterization of new inhibitors of the Escherichia coli MurA enzyme.
The bacterial enzyme MurA catalyzes the transfer of enolpyruvate from phosphoenolpyruvate (PEP) to uridine diphospho-N-acetylglucosamine (UNAG), which is the first committed step of bacterial cell wall biosynthesis. From high-throughput screening of a chemical library, three novel inhibitors of the Escherichia coli MurA enzyme were identified: the cyclic disulfide RWJ-3981, the purine analog RWJ-140998, and the pyrazolopyrimidine RWJ-110192. When MurA was preincubated with inhibitor, followed by addition of UNAG and PEP, the 50% inhibitory concentrations (IC(50)s) were 0.2 to 0.9 microM, compared to 8.8 microM for the known MurA inhibitor, fosfomycin. The three compounds exhibited MICs of 4 to 32 microg/ml against Staphylococcus aureus; however, the inhibition of DNA, RNA, and protein synthesis in addition to peptidoglycan synthesis by all three inhibitors indicated that antibacterial activity was not due specifically to MurA inhibition. The presence of UNAG during the MurA and inhibitor preincubation lowered the IC(50) at least fivefold, suggesting that, like fosfomycin, the three compounds may interact with the enzyme in a specific fashion that is enhanced by UNAG. Ultrafiltration and mass spectrometry experiments suggested that the compounds were tightly, but not covalently, associated with MurA. Molecular modeling studies demonstrated that the compounds could fit into the site occupied by fosfomycin; exposure of MurA to each compound reduced the labeling of MurA by tritiated fosfomycin. Taken together, the evidence indicates that these inhibitors may bind noncovalently to the MurA enzyme, at or near the site where fosfomycin binds.
Alkyl and Aryl Transferases↗
Antibiotherapy of Serratia marcescens septicemia in children.
The clinical and bacteriological response of 38 treatments performed on 24 children (11 of them neonates) carrying out separate treatments with carbenicillin (2 treatments), gentamicin [4], fosfomycin [6], and associated treatments with gentamicin plus carbenicillin [6], fosfomycin plus gentamicin [18] and fosfomycin plus carbenicillin [2] are considered. The clinical cure was obtained in 21 children (87.5%). The most effective treatment was fosfomycin plus gentamicin; both antibiotics showed synergism in vitro on isolated Serratia strains. A dosage of 75 mg/kg fosfomycin enables serum levels of about 32 mug/ml during 4-5 h, being this level higher to the MIC of all isolated strains of S. marcescens.
Anti-Bacterial Agents↗
Isolation of fluoroquinolone-resistant rectal Escherichia coli after treatment of acute uncomplicated cystitis.
OBJECTIVES: Given increasing rates of co-trimoxazole resistance among uropathogens causing acute uncomplicated cystitis, fluoroquinolones, nitrofurantoin and fosfomycin are often considered as alternative empirical therapy. The choice between these drugs should depend in part on whether they are associated with the isolation of drug-resistant microbial flora. We conducted a randomized treatment trial to assess the effects of ciprofloxacin, nitrofurantoin and fosfomycin on the rectal microbial flora of women with acute uncomplicated cystitis, including isolation of fluoroquinolone-resistant strains. METHODS: Pre-menopausal women presenting with acute uncomplicated cystitis were randomized to treatment with 3 days of ciprofloxacin, 7 days of nitrofurantoin, or a single dose of fosfomycin. Women were followed for 1 month for evaluation of clinical and microbiological responses as well as for isolation of resistant rectal E. coli. RESULTS: Sixty-two women (25 ciprofloxacin, 17 nitrofurantoin, 20 fosfomycin) were enrolled and eligible for analysis. All three regimens were well tolerated and resulted in >90% clinical and bacteriological cure. The prevalence of rectal E. coli was markedly decreased by ciprofloxacin and fosfomycin, but not by nitrofurantoin. One woman treated with ciprofloxacin had emergence of two ciprofloxacin-resistant rectal E. coli strains within 10 days of completing therapy. No emergence of resistance was observed in the other two treatment groups. CONCLUSIONS: This study demonstrates that fluoroquinolone-resistant E. coli remain infrequent in the rectal flora of women with uncomplicated cystitis in Seattle. However, a 3 day course of a fluoroquinolone for treatment of uncomplicated cystitis was followed by isolation of fluoroquinolone-resistant rectal E. coli in one patient.
Acute Disease↗
Gentamicin- and methicillin-resistant, clinical isolates of Staphylococcus aureus: comparative in vitro and in vivo efficacy of alternative antimicrobial drugs.
Six representative clinical isolates of gentamicin- and methicillin-resistant (GRMR) Staphylococcus aureus, constituting phage groups II and III, were susceptible only to amikacin, cefamandole, clindamycin, fosfomycin, fusidic acid, netilmicin, nitrofurantoin, trimethoprim-sulfamethoxazole, and vancomycin (Bauer-Kirby test). With few exceptions, the minimal bactericidal concentrations of the beta-lactam and aminoglycoside antibiotics tested, fusidic acid, and irregularly those of vancomycin, but not those of fosfomycin and rifampin, exceeded minimal inhibitory concentrations values by at least 8-fold. In vitro, combinations of rifampin with cefamandole, cefazolin, cefotaxime, erythromycin, fosfomycin, fusidic acid, netilmicin, and vancomycin yielded indifferent effects. The GRMR S. aureus strains were refractory against 50, 65, and 80 vol% of fresh defibrinated blood; following reduction of viable counts at 2 h (greater than or equal to 90%), rebound growth invariably occurred within 4 h after exposure. Combined human blood (55 vol%)-antibiotic assays revealed rifampin as the most effective drug, followed by vancomycin, fusidic acid, and cefamandole, in that order. Blood plus cefotaxime, cefazolin, or netilmicin yielded indifferent effects; fosfomycin failed in vitro. In terms of speed of recovery and survival data (chi 2 test), cyclophosphamide-pretreated, i.e., leukopenic NMRI mice responded best to chemotherapy with rifampin, followed by vancomycin, cefamandole, netilmicin, and fosfomycin, in that order; cefazolin yielded variable results.
Animals↗
Pharmacokinetic and pharmacodynamic aspects of antimicrobial agents for the treatment of uncomplicated urinary tract infections.
Uncomplicated urinary tract infections (UTI) are treated with beta-lactams, co-trimoxazole, quinolones and fosfomycin tromethamine. Due to increasing resistance of causative pathogens, antibiotics should be used by considering their pharmacodynamic and pharmacokinetic characteristics. beta-lactams have time-dependent activity and should not be used once-daily. Co-trimoxazole should be restricted due to increasing chemoresistance. Fluoroquinolones play a primary role in the treatment of serious and complicated infections. Fosfomycin tromethamine is active against most urinary tract pathogens. In vitro time-kill kinetics of fosfomycin against Escherichia coli and Proteus mirabilis showed primarily concentration-dependent activity, with a prolonged post-antibiotic effect (3.4 to 4.7h). Based on these results a single 3g dose of fosfomycin guarantees optimal efficacy against common uropathogens with an AUC(urine)/MIC ratio of 500.
Anti-Infective Agents↗
Role of the loop containing residue 115 in the induced-fit mechanism of the bacterial cell wall biosynthetic enzyme MurA.
The induced-fit mechanism in Enterobacter cloacae MurA has been investigated by kinetic studies and X-ray crystallography. The antibiotic fosfomycin, an irreversible inhibitor of MurA, induced a structural change in UDP-N-acetylglucosamine (UDPGlcNAc)-liganded enzyme with a time dependence similar to that observed for the inactivation progress. The mechanism of action of fosfomycin on MurA appeared to be of the bimolecular type, the overall rate constants of inactivation and structural change being = 104 M(-1) s(-1) and = 85 M(-1) s(-1), respectively. Fosfomycin as well as the second MurA substrate, phosphoenolpyruvate (PEP), are known to interact with the side chain of Cys115. Like wild-type MurA, the catalytically inactive single-site mutant protein Cys115Ser structurally interacted with UDPGlcNAc in a rapidly reversible reaction. However, in contrast to wild-type enzyme, binding of PEP to mutant protein induced a rate-limited, biphasic structural change. Fosfomycin did not affect the structure of the mutant protein. The crystal structure of unliganded Cys115Ser MurA at 1.9 A resolution revealed that the overall conformation of the loop comprising residues 112-121 is not influenced by the mutation. However, other than Cys115 in wild-type MurA, Ser115 exhibits two distinct side-chain conformations. A detailed view on the loop revealed the existence of an elaborate hydrogen-bonding network mainly supplied by water molecules, presumably stabilizing its conformation in the unliganded state. The comparison between the known crystal structures of MurA, together with the kinetic data obtained, suggest intermediate conformational states in the MurA reaction, in which the loop undergoes multiple structural changes upon ligand binding.
Alkyl and Aryl Transferases↗
Quinolone antibiotics induce Shiga toxin-encoding bacteriophages, toxin production, and death in mice.
Shiga toxin-producing Escherichia coli (STEC) cause significant disease; treatment is supportive and antibiotic use is controversial. Ciprofloxacin but not fosfomycin causes Shiga toxin-encoding bacteriophage induction and enhanced Shiga toxin (Stx) production from E. coli O157:H7 in vitro. The potential clinical relevance of this was examined in mice colonized with E. coli O157:H7 and given either ciprofloxacin or fosfomycin. Both antibiotics caused a reduction in fecal STEC. However, animals treated with ciprofloxacin had a marked increase in free fecal Stx, associated with death in two-thirds of the mice, whereas fosfomycin did not. Experiments that used a kanamycin-marked Stx2 prophage demonstrated that ciprofloxacin, but not fosfomycin, caused enhanced intraintestinal transfer of Stx2 prophage from one E. coli to another. These observations suggest that treatment of human STEC infection with bacteriophage-inducing antibiotics, such as fluoroquinolones, may have significant adverse clinical consequences and that fluoroquinolone antibiotics may enhance the movement of virulence factors in vivo.
Animals↗
Mapping of a genetic locus that affects glycerol 3-phosphate transport in Bacillus subtilis.
Two types of fosfomycin-resistant mutants of Bacillus subtilis were isolated. Mutants of the first type (GlpT mutants) were resistant to at least 200 microgram of fosfomycin per ml and failed to take up exogenous glycerol 3-phosphate. Mutants of the second type were resistant to lower concentrations of fosfomycin and transported glycerol-3-phosphate as efficiently as wild-type bacteria. The glpT mutations, but not the mutations in the second type of fosfomycin-resistant mutants, map in the cysA-aroI region of the B. subtilis chromosome.
Bacillus subtilis↗
FR-31564, a new phosphonic acid antibiotic: bacterial resistance and membrane permeability.
Mutants which acquired resistance to FR-31564 were also resistant to fosfomycin and vice versa. Some exceptions to cross-resistance were found among clinical isolates of certain species. FR-31564 was found to be incorporated into bacterial cells more efficiently than fosfomycin although the extent of incorporation varied among species. In particular, the uptake rate of FR-31564 by a strain of Pseudomonas aeruginosa was ten times that of fosfomycin. The uptake rate of FR-31564 by both FR-31564- and fosfomycin-resistant mutants was less than one-tenth of that by the parent strain. FR-31564 was scarcely inactivated in the culture broths of FR-31564-resistant strains. All of the FR-31564-resistant mutants of P. aeruginosa came under the classification of strains lacking an L-alpha-glycerophosphate transport system.
Anti-Bacterial Agents↗
Fosfomycin/metronidazole compared with doxycycline/metronidazole for the prophylaxis of infection after elective colorectal surgery. A randomised double-blind multicentre trial in 517 patients.
OBJECTIVE: To find out if fosfomycin together with metronidazole was any better than doxycycline with metronidazole for the prophylaxis of infection before elective colorectal operations. DESIGN: Multicentre, double blind, random control trial. SETTING: Nine Swedish hospitals. SUBJECTS-559 patients admitted for elective colorectal operations. INTERVENTIONS: Fosfomycin 8 g and metronidazole 1 g before operation and fosfomycin 8 g eight hours afterwards, or doxycycline 400 mg and metronidazole 1 g before operation, and placebo eight hours afterwards. MAIN OUTCOME MEASURES: Incidence of all types of infection, mortality, and side effects. RESULTS: There were no significant differences between the groups for any of the outcome measures studied, the overall abdominal infection rates (wound, deep, and septicaemia) being 4.6% and 7.4%, and the remote infection rates (pneumonia, urinary tract, and central venous line) 15.1% and 12.8%, respectively. Of the predictors studied, only duration of operation was significantly related to risk of infection. CONCLUSION: The combination of fosfomycin and metronidazole was as safe and effective as that of doxycycline and metronidazole in preventing infections after elective colorectal operations.
Aged↗
The efficacy of a hydroxyapatite composite as a biodegradable antibiotic delivery system.
Local biodegradable carriers have been studied for use as a skeletal drug delivery system. This study investigated the efficacy of a local biodegradable composite composed of hydroxyapatite, plaster of Paris, and chitosan impregnated with antibiotics to treat methicillin-resistant Staphylococcus aureus. The composite, impregnated with vancomycin, fosfomycin, or sodium fusidate was tested for its sustained elution characteristics during 3 months and compared with similarly impregnated polymethylmethacrylate using the modified disc diffusion technique. Physicochemical properties using scanning electron microscopy and xray diffraction analysis of each preparation also were analyzed. Vancomycin and fosfomycin incorporated into the hydroxyapatite composite inhibited the organism for 3 months, whereas sodium fusidate was effective only for 3 weeks. Vancomycin and fosfomycin loaded into the hydroxyapatite composite had a significantly better inhibitive effect than when loaded in polymethylmethacrylate, whereas sodium fusidate loaded in polymethylmethacrylate showed a significantly better inhibitive effect than when loaded in the hydroxyapatite composite. Scanning electron microscopy and xray diffraction analysis elucidated the patterns of each drug release profile. The local hydroxyapatite composite is a promising local biodegradable delivery system for vancomycin and fosfomycin, whereas PMMA is a better carrier for sodium fusidate in treating methicillin-resistant staphylococcus aureus osteomyelitis.
Anti-Bacterial Agents↗