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PubMed2002

Time- and dose-dependent effect of fosfomycin on suppression of infection-induced endotoxin shock in mice.

Therapeutic effects of fosfomycin (FOF) and imipenem (IPM) were investigated in a novel model for endotoxin shock that was caused by intraperitoneal (i.p.) infection with 10(8) colony forming units of attenuated Salmonella typhimurium. Acute lethal shock was observed in BALB/c and ddY but not in lipopolysaccharide (LPS)-nonresponder BALB/lps(d) mice. Effects of FOF, but not its enantiomer, and IPM were dose- and time-dependent, since therapeutic efficacy was demonstrated in mice injected i.p. or orally at doses of more than 20 mg/kg 15 min before or 1 h after infection. Treatment with FOF 1 h postinfection (p.i.) resulted in significant decreases in bacterial numbers in spleen and liver, suggesting that the antimicrobial activity of FOF seems to closely correlate to suppression of infection-induced lethal shock. Regarding coagulation systems, FOF inhibited increase in the prothrombin time but upregulated fibrinogen concentration. Plasma levels of LPS released from bacilli were significantly higher in FOF- than IPM-treated mice and infection controls, but both antibiotics showed similar efficacy in protection.

Animals↗
PubMed1990

Sodium and pH dependent carrier-mediated transport of antibiotic, fosfomycin, in the rat intestinal brush-border membrane.

The mechanism of intestinal absorption of an antimicrobial agent, fosfomycin (FOM), was investigated in rats using small intestinal brush-border membrane vesicles (BBMV). The uptake of [3H]FOM by BBMV was osmolarity- and temperature-sensitive and showed apparently saturable uptake kinetics consistent with the Michaelis-Menten equation, having Kt = 15.3 mM and Jmax = 7.78 nmol/30 s/mg protein at 37 degrees C. An overshoot uptake of FOM was observed in the presence of an inwardly direct Na+ gradient. The replacement of extravesicular Na+ with choline or mannitol significantly reduced the uptake. An addition of a protonophore, FCCP, significantly decreased the initial uptake of FOM in the absence of Na+ gradient but in the presence of a H+ gradient (pHin = 7.5, pHout = 6.0), whereas in the absence of a H+ gradient no significant difference was observed between the uptakes at an acidic pH (pHin = pHout = 6.0) and a neutral pH (pHin = pHout = 7.5). An inside negative potassium diffusion potential induced by valinomycin enhanced significantly the uptake of FOM. The uptake of FOM in the presence of both Na(+)- and H(+)-gradients was significantly inhibited by phosphate, arsenate and phosphonoformic acid (PFA), which are specific inhibitors of phosphate transport, but not by D-glucose. Based on these results, it is concluded that FOM transport in the small intestine is partially shared with the Na(+)-phosphate cotransport system and in part occurs via a H(+)-gradient dependent carrier-mediated system.

Animals↗
PubMed1991

Paracellular and transcellular permeabilities of fosfomycin across small intestinal membrane of rat and rabbit by voltage-clamp method.

The permeability of fosfomycin (FOM), which is a low molecular weight and water-soluble antibiotic, across rat and rabbit jejunal membrane was investigated on a paracellular route and a transcellular route separated by voltage-clamp method. It was determined that FOM permeates through these two routes in both animals. Under a physiologically normal condition, the transmucosal electrical potential difference (about 2 mV), the contribution of the transcellular route to FOM membrane permeability was greater than that of the paracellular route. The transcellular permeability was significantly reduced in the presence of inorganic phosphate. The inhibitory effects of the inorganic phosphate coincided with our reports on FOM uptake by rat jejunal brush-border membrane vesicles in vitro and on FOM absorption by rat jejunal single-pass perfusion in situ.

Algorithms↗
PubMed1991

Effect of carrier-mediated transport system on intestinal fosfomycin absorption in situ and in vivo.

Intestinal absorption mechanism of fosfomycin (FOM), a water-soluble and small molecular antibiotic, at the clinical dose level was examined by both in situ single-pass perfusion technique of rat small intestine and oral administration in rat in vivo. Analyzing the luminal concentration-dependence of FOM absorption rates in situ by the equation composed of two terms of carrier transport of Michaelis-Menten type and simple-diffusion, apparent Michaelis constant (Kt), maximal transport velocity (Jmax), and first-order diffusive absorption clearance (Kd) were 1.13 mM, 2.54 nmol/min/cm length, and 0.551 microliters/min/cm length, respectively. At the low FOM concentration in the lumen (0.1 mM), its absorption was reduced to about 60% of the control by inorganic phosphate ion at 1.0 mM in the same manner as the uptake in brush border membrane vesicles of rat small intestine (BBMVs) in vitro. Both the glycol form of FOM at 10 mM, the hydrolyzed metabolite of FOM in the stomach juice, and FOM itself at 10 mM reduced FOM absorption by about 50%, indicating the metabolite to be transported by the same carriers as those of FOM. At the higher FOM concentration (5 mM), its absorption was not reduced by any inhibitor described above. No inhibitory effect of 50 mM phosphate ion on FOM absorption following the oral dosing of 20 mg/kg FOM was found. It was concluded that FOM absorption at the clinical dose (10-20 mg/kg) is barely inhibited by the carrier-mediated system via phosphate transport system observed in the in vitro BBMVs.

Animals↗
PubMed1992

Mechanisms of intestinal absorption of the antibiotic, fosfomycin, in brush-border membrane vesicles in rabbits and humans.

In order to clarify the mechanism of intestinal absorption of an antibiotic, fosfomycin (FOM), the uptakes of FOM by rabbit and human small intestinal brush-border membrane vesicles (BBMV) were studied. The initial uptake of FOM by BBMV at 15 s was saturable at a higher concentration of FOM. The kinetic parameters at 37 degrees C of the saturable uptake expressed by the Michaelis-Menten equation were Kt = 5.17 mM and Jmax = 3.88 nmol/15 s/mg protein for rabbits, and Kt = 4.03 mM and Jmax = 1.90 nmol/15 s/mg protein for humans. The most efficient uptake was observed in the presence of both inward-directed Na(+)- and H(+)-gradients in both mammals. The uptake of FOM was inhibited by inorganic phosphate, FOM glycol which is a degradation product of FOM in the gastric juice and specific inhibitors of phosphate transport such as arsenate and phosphonoacetic acid. These findings confirmed that FOM absorption from rabbit and human small intestines is associated with the phosphate transport system. These transport phenomena of FOM are in close agreement with those obtained previously in rat BBMV studies. Judging from the results obtained for three mammalian species, rat, rabbit and human, it was concluded that carrier-mediated transport via the phosphate transport system is a very important pathway of intestinal absorption of FOM.

Animals↗
PubMed1975

Charactertization of spontaneous fosfomycin (phosphonomycin)-resistant cells of Escherichia coli B in vitro.

The characteristics of spontaneous fosfomycin-resistant cells isolated in vitro were investigated. Distribution of resistance level to the drug in Escherichia coli B was thought to be broad and, for this reason, resistance to the drug seemed to develope easily in vitro. In the process of isolating the resistant cells, two groups of cells, differing in colony size, were distinguished. Smaller colony-forming cells appeared more frequently than Larger colony-forming ones. Many of the former seemed to be slow growers and decreased simultaneously in utilization of several carbohydrates. One of the Smaller colony-forming isolates was distinctly different from glp T- or uhp-.

Anti-Bacterial Agents↗
PubMed1982

Synergistic effects of a macrolide and a cell wall-affecting antibiotic on Pseudomonas aeruginosa in vitro and in vivo. 2. Combined effects of a macrolide with a fosfomycin and an aminoglycoside antibiotic.

Synergistic effects of the cell wall-affecting antibiotics, dibekacin (DKB) and fosfomycin (FOM) and a macrolide antibiotic, midecamycin (MDM) or its derivative 9,3"-di-O-acetylmidecamycin (MOM) against Pseudomonas aeruginosa were investigated in vitro and in vivo. Synergistic effects were evaluated by estimating the number of viable bacteria at varying intervals after the two kinds of antibiotics were added to the logarithmic phase of the bacterial solution. Six hours after addition of antibiotic, the viable bacterial count of the culture treated with FOM and MOM underwent 2 log reduction compared to that which treated with FOM alone. Thus synergistic effect was significant. The number of viable bacteria treated with DKB and MDM showed slight reduction at 3 hours after addition of the two antibiotics and a marked reduction was noted after 20 hours compared with the control. Synergistic action was also demonstrated in in vivo experiments using mice. Three experimental mouse infection models, intraperitoneal infection, subcutaneous infection with carrageenan solution and burn infection were used. FOM was administered subcutaneously. DKB was administered intramuscularly. MDM or MOM was administered by the oral route. In all three experiments the survival rate of infected mice treated with FOM and MOM increased significantly compared to control mice. Similar synergistic effect was also obtained with DKB and MDM.

Animals↗
PubMed2000

[Antibacterial activity of fosfomycin against the causative bacteria isolated from bacterial enteritis].

The in vitro antibacterial activities of fosfomycin (FOM) and 3 fluoroquinolones against Salmonella spp., pathogenic Escherichia coli, Campylobacter spp. and Shigella spp. were investigated. The activity upon the environmental condition in the inflammation was compared with standard condition in vitro. On standard condition, the MIC90 of tosfloxacin (TFLX), norfloxacin (NFLX) and levofloxacin (LVFX) against E. coli (77 strains), Shigella spp. (50) and Salmonella spp. (41) were < or = 0.025-0.10, 0.10, and 0.05 microgram/ml, respectively. The MIC90 of FOM against those organisms was 0.39-1.56 micrograms/ml. The MIC90 of TFLX, NFLX, LVFX against Campylobacter spp. were 6.25, 100 and 3.13 micrograms/ml, respectively. The MIC90 of FOM was 50 micrograms/ml. The activity of FOM was unaffected by pH and in anaerobic condition. On the other hand, the activity of NFLX was decreased in low pH and in anaerobic condition. In the presence of horse blood and addition of Na+, the activities of both agents were unaffected. These results suggested that FOM is equally active with or superior to fluoroquinolone in the intestinal infection treatment.

Anti-Bacterial Agents↗
PubMed2001

[The epoxidation of cis-propenylphophonic acid to fosfomycin by Pencillium sp].

One strain of Penicillium sp. F5, found from soil sample, was able to stereo-specific epoxidation of cis-propenylphosphonic acid(PPOH) to fosfomycin[(-)-(1R, 2S)-1, 2-epoxypropylphosphonic acid, FOM] during the cultivation. The product (FOM) was identified by thin layer chromatography and microbiological assay. Under the culture conditions of 28 degrees C pH7.5 and 280 r/min, 0.3% concentration of PPOH, reached a level of 2.2 mg/ml of FoM and the yield was 41%. When the PPOH concentration was 0.6%, the yield was 8%.

Biotransformation↗
PubMed2003

[Antimicrobial activity of fosfomycin against beta-lactamase-producing methicillin-sensitive Staphylococcus aureus and methicillin-sensitive coagulase-negative staphylococci].

Antimicrobial activity of fosfomycin (FOM), cefazolin (CEZ), cefmetazole (CMZ), cefotiam (CTM) and piperacillin (PIPC) against clinical isolates of methicillin-sensitive Staphylococcus aureus (MSSA) (beta-lactamase-producing or non-producing) and methicillin-sensitive coagulase-negative Staphylococci (MSCNS) (beta-lactamase-producing or non-producing) were determined to make clear the differences in antimicrobial activity of FOM and beta-lactam antibiotics. The antimicrobial activity of PIPC against beta-lactamase-producing strains of MSSA was lower than that against non-producing ones, judging from the distribution patterns of susceptibility of the strains to PIPC. There were no differences in the antimicrobial activity of FOM, CEZ and CMZ for the producing and non-producing strains. The activity of FOM against MSCNS was comparable to that against MSSA, although those of CEZ, CMZ, CTM and PIPC were decreased. FOM, CEZ, CMZ and CTM showed bactericidal activity against TH4278 (MIC [microgram/ml]: FOM, 1; CEZ, 0.5; CMZ, 1; CTM, 0.5; PIPC, 1) of beta-lactamase-producing MSSA at 1 microgram/ml for 6 h, but PIPC did not at the same condition. FOM and CMZ at MIC suppressed regrowth of the strain, but CEZ, CTM and PIPC did not. In conclusion, FOM, which is not affected by beta-lactamase, demonstrated strong bactericidal activity at low concentration against the beta-lactam-resistant strains due to beta-lactamase production.

Anti-Bacterial Agents↗
PubMed1992

[Combined effects of arbekacin with other antibiotics against methicillin-resistant Staphylococcus aureus. I. The combined effect of arbekacin with fosfomycin or clavulanic acid/ticarcillin].

As arbekacin (ABK) has a highly potent antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA), its combined effects with fosfomycin (FOM) and clavulanic acid/ticarcillin (CVA/TIPC) against MRSA were examined. The obtained results are summarized as follows. 1. Against MRSA either combination, FOM+ABK or CVA/TIPC+ABK showed a strong antibacterial effect at the MIC or the sub MIC of ABK in the blood expected from clinical observations. The MIC of ABK by the combination use seemed to be equivalent to the MBC value. 2. Effective concentrations of antibiotics in these combinations appeared to be strongly dependent on the effective concentration of ABK and less dependent on that of FOM or CVA/TIPC. Therefore, the antibacterial activity of a combination seems to mostly depend on the antibacterial activity and the concentration of ABK. 3. As FOM and CVA/TIPC have antibacterial activities against Pseudomonas aeruginosa, combinations of ABK with these antibiotics are likely to be effective against double infection with P. aeruginosa in MRSA infected patients.

Aminoglycosides↗
PubMed2003

[Activity of fosfomycin against Escherichia coli O157:H7--morphological changes and production of Shiga toxins].

We examined the effects of fosfomycin (FOM), norfloxacin (NFLX), kanamycin (KM), chloramphenicol (CP), and ampicillin (ABPC) on the morphology of E. coli O157:H7, and the accumulation (cell fraction) and release (medium fraction) of Shiga toxins (Stxs: Stx1 and Stx2) in E. coli O157:H7 three hours after treatment with the antibiotics. For each drug, 16 MIC was used for measurement of the activity at a high drug concentration and 1/4 MIC at a low concentration. At 16 MIC, cell wall synthesis inhibitors, FOM and ABPC, strongly induced lysis of the cell of E. coli KU3342, a strain of E. coli O157:H7. The release of Stx1 was observed, but there was no accumulation of Stxs. Nucleic acid synthesis inhibitor NFLX and protein synthesis inhibitor KM induced partial lysis and short filamentation of the cell, and the accumulation and release of Stxs were low. No morphological change was observed after treatment with protein synthesis inhibitor CP, but the accumulation and release of Stxs by CP were low. At 1/4 MIC, FOM induced strong lysis of the cell, and the release of Stx1 was observed, but there was no accumulation of Stxs. ABPC and NFLX had weak lytic reaction, but induced filamentation of the cell, and the accumulation and release of Stxs were observed. In particular, NFLX significantly induced accumulation and release of Stx2. KM and CP had no effect on the morphology of the cells, and the accumulation of Stx1 was not observed, but there was no release of Stxs. The above-mentioned results support the clinical efficacy of FOM in the control of enterohoemorhagic E. coli infections.

Ampicillin↗
PubMed2005

[Antimicrobial activity of fosfomycin under various conditions against standard strains, beta-lactam resistant strains, and multidrug efflux system mutants].

The purpose of this study was to evaluate the possible benefit of fosfomycin (FOM) as prophylactic antibiotic in terms of antimicrobial activity and the potential of inducibility of beta-lactamase, compared with cefazolin, cefotiam, cefmetazole, and piperacillin that are commonly used as perioperative agents. The in vitro activity of FOM against aerobic Gram-negative bacteria using Mueller-Hinton agar or nutrient agar supplemented with glucose-6-phosphate (G6P) as tested medium increased within a range from 2 to 256 times the activity in the medium without G6P. However, the susceptibility of Gram-positive bacteria to FOM remained largely unchanged with or without G6P. There was no aerobic- or anaerobic-bacteria which changed susceptibility against beta-lactam antibiotics under various tested medium conditions. FOM demonstrated strong bactericidal activity against Escherichia coli and Pseudomonas aeruginosa in a dose dependent manner, and decreased viable cell counts of Staphylococcus aureus. In the case of P. aeruginosa, transmission electron micrographs study revealed that numerous lysed cells were present 2 hours after treatment with FOM at four times the MIC. First and second generation cephalosporins induced AmpC-type beta-lactamase in a dose dependent manner among beta-lactamase inducible strains of P. aeruginosa and Enterobacter cloacae. On the other hand, inducible activity of FOM on beta-lactamase production was less than 1/25 to 1/65 compared with those of cephalosporins. In addition, FOM maintained strong antimicrobial activity for over then 20 years after marketing, because of the excellent stability against various types of beta-lactamase produced by plasmid-carrying bacteria and clinical isolates. FOM was not extruded by four types of efflux systems, such as MexAB-OprM, MexCD-OprJ, MexXY/ OprM and MexEF-OprN, however beta-lactam antibiotics were substrates of MexAB-OprM and MexCD-OprJ. In conclusion, FOM provides adequate coverage for both aerobic Gram-positive and Gram-negative bacteria causing postoperative infections. Further, FOM would not select/concentrate beta-lactamase producing bacteria in the clinical fields and would not be a substrate for multidrug efflux system of P. aeruginosa.

Anti-Bacterial Agents↗
PubMed1991

[Clinical evaluation of a combination treatment with cefminox and fosfomycin for infections complicated in patients with hematological disorders].

We evaluated clinical effects and toxicities of a combination treatment with cefminox (CMNX) and fosfomycin (FOM) for infections complicated with hematological disorders in 56 patients. Among those, 52 patients including 22 with malignant lymphoma, 19 with acute leukemia, and 11 with other hematological disorders were evaluable. Excellent and good responses were obtained in 33 (63.5%) of the 52 patients. This treatment was also effective in 5 of 9 cases in which granulocyte counts were less than 500/mm3 through the course of administration. Side effects were observed in only one patient. Mild nausea occurred but was not serious. These results indicate that the combination of CMNX and FOM is an effective and safe regimen for the treatment of infections complicated in patients with hematological disorders.

Adult↗
PubMed1991

[A study of the absorption and excretion of fosfomycin sodium in children].

Fosfomycin sodium (FOM-Na, Forocyle-S) was administered at 25 mg/kg or 50 mg/kg to 15 children between the ages of 3 and 15 through intravenous injection or through 1 hour intravenous drip infusion, and concentrations in blood serum and excretion through urine were examined and a pharmacokinetic analysis was carried out using the one-compartment model. 1. Average concentrations in the blood serum after injections with 25 mg/kg and 50 mg/kg were 55.3 +/- 6.3 micrograms/ml and 118.8 +/- 31.1 micrograms/kg 30 minutes after injection, respectively, and their half-lives were 1.04 +/- 0.15 hours and 0.98 +/- 0.17 hours, respectively. Six hours after injection, the levels were 2.7 +/- 1.6 micrograms/kg and 6.2 +/- 5.5 micrograms/kg, respectively. With 1 hour intravenous drip infusion of 25 mg/kg and 50 mg/kg, average concentrations the blood serum were 34.2 +/- 14.9 micrograms/ml and 89.7 +/- 6.7 micrograms/ml, respectively, and their half-lives were 0.87 +/- 0.24 hour and 0.69 +/- 0.10 hour, respectively. Six hours after the administration, the levels were 2.7 +/- 1.8 micrograms/ml and 6.7 +/- 0.8 micrograms/ml. There was a clear dose response in the concentration levels in the blood in those given the drug at 25 mg/kg and 50 mg/kg in either method of administration. 2. Average levels in urine after injection of 25 mg/kg and 50 mg/kg were 5,778 +/- 2,257 micrograms/ml and 6,268 +/- 3,329 micrograms/ml 0-2 hours after administration, respectively, and average levels at 4-6 hours were 701 +/- 765 micrograms/ml and 1,588 +/- 1,324 micrograms/ml, respectively. Average excretion, rates into the urine were 72.8 +/- 11.0 and 73.9 +/- 11.1%, respectively. In case of 1 hour drips infusion of 25 mg/kg and 50 mg/kg, average concentrations in the urine 0-2 hours after administration were 3,570 +/- 1,540 micrograms/ml and 11,800 micrograms/ml, respectively, and averages for 4-6 hours were 211 +/- 124 micrograms/ml and 1,300 micrograms/ml. Average rates of excretion into the urine for the first group was 57.9 +/- 16.3% and the second group was 78.4%. Clear dose response was observed in changes of drug concentration levels in the urine with 25 mg/kg and 50 mg/kg doses through either administration method, and in terms of excretion into the urine, no noticeable differences were observed between the different amounts administered or different administration methods.(ABSTRACT TRUNCATED AT 400 WORDS)

Child↗
PubMed1991

[Bacteriological study on fosfomycin against organisms clinically isolated from paranasal sinusitis].

Multi-center bacteriological and clinical studies on fosfomycin (FOM) nasal solution were performed in subjects with paranasal sinusitis from January, 1988 to May, 1990. In these studies, we were exclusively responsible for bacterial isolation from clinical sources, bacterial identification and the determination of drug susceptibility. Before local administration of FOM nasal solution, many strains of various bacterial species were isolated from sources totalling 396 cases involved in phase II clinical studies, dose-finding and open clinical studies. From antibacterial activities of FOM against those isolates, we obtained the following conclusions. 1. Among the 447 isolates, Streptococcus spp. occupied 25.7%, Staphylococcus spp. 21.7% and anaerobic Gram-positive cocci (GPC) 13.6%, showing high detection frequency of aerobic and anaerobic GPC. Next to these, Haemophilus influenzae, Pseudomonas aeruginosa, Klebsiella spp. and Branhamella catarrhalis also were often obtained. 2. After exclusion of possibly contaminating strains which might have entered into cultures at samplings or transfers, the MIC50 and the MIC80 of FOM against the remaining 354 isolates were determined to be 12.5 and 25 micrograms/ml, respectively, indicating that local use of FOM would be fully effective to eradicate most of the bacteria. 3. FOM nasal solution showed sufficient eradication efficacy against most clinical isolates of possible causative organisms of paranasal sinusitis, and appeared to be useful as a topical preparation for the treatment of this disease.

Administration, Intranasal↗
PubMed1991

[Clinical studies and morphological response on ST-95 (fosfomycin)].

Clinical effects of ST-95 (fosfomycin) on infections of the urinary tract were studied on the basis of morphological changes of the urinary bacteria. The subjects were 22 inpatients with complex infections of the urinary tract. ST-95 was dissolved in physiologic saline (2 g/100 ml) and administered intravenously by drip infusion over a 1-hour period twice daily for 5 days. According to the UTI criteria, the treatment was effective in 13 (81%) of the 16 evaluable cases. The present effectiveness in 8 patients with chronic catheterization was 75%. No side effects were observed in any patient. Among the laboratory data, GOT and GPT were slightly increased in 1 patient, but their relations with the treatment were unknown. In one patient (P. vulgaris; MIC: 12.5 micrograms/ml), changes in the urinary ST-95 concentration, viable bacterial count, and morphology of the bacteria were studied after the initial administration. The urinary viable cell count was 1.5 x 10(7) cells/ml before administration, but it was reduced to 1.6 x 10(4) cells/ml at the end of the 1-hour infusion, and decreased progressively thereafter to complete disappearance after 12 hours. Under differential interference microscopy, filamentous debris of bacteria and spherical bacteria with irregular surface were observed from immediately after the end of the administration. By transmission electron microscopy, the cell wall showed a number of projections with formation of vacuolar structures in the space between the cell wall and the irregularly-shaped cytoplasms. In conclusion, the results of administration of ST-95 in complex infections of the urinary tract were satisfactory. The morphological changes of the bacteria suggested that this agent acts at an early stage of cell wall synthesis.

Bacteria↗
PubMed1990

[Combination effects of fosfomycin and other oral antimicrobial agents against methicillin-resistant Staphylococcus aureus].

Combination effects of fosfomycin (FOM) and other oral antimicrobial agents were studied against methicillin-resistant Staphylococcus aureus (MRSA) (methicillin: minimal inhibitory concentration (MIC) greater than or equal to 12.5 micrograms/ml) isolated from skin and skin structure infections. The fractional inhibitory concentration (FIC) index equal to or less than 0.5 was seen in 63.0% of 27 MRSA strains for FOM and minocycline combination, in 44.4% for FOM and cefatrizine, in 44.4% for FOM and cefaclor, in 40.7% for FOM and cefalexin, in 37.0% for FOM and doxycycline, in 29.6% for FOM and erythromycin, in 22.2% for FOM and rokitamycin, in 18.5% for FOM and ofloxacin, in 14.8% for FOM and sultamicillin, in 11.1% for FOM and clavulanic acid/amoxicillin. The combination effects of FOM and minocyclin, or FOM and cephalosporins were higher than other combinations with FOM. Combination of FOM with other antibiotics could be a useful way to treat MRSA skin and skin structure infections.

Administration, Oral↗