A super-infection in the cornea caused by Stemphylium, Acremonium, and α-Streptococcus.

BACKGROUND: Polymicrobial keratitis with fungus and bacteria can lead to blindness and is challenging to treat. Here, we introduce a case of fungal keratitis caused by two different strains in addition to definite bacterial super-infection caused by an α-Streptococcus sp., and describe the importance of microscopic examination. CASE PRESENTATION: A 74-year-old woman, who had a past history of infection with leprosy, presented with conjunctival hyperaemia, pain, and corneal opacity in her right eye. Under the presumptive diagnosis of infectious keratitis, corneal scrapings were stained by various reagents and inoculated on several agar plates. Microscopic findings of the scrapings revealed fungi and a small number of Gram-positive cocci. Multiple anti-fungal therapies with levofloxacin ophthalmic solution were administered. Although empiric treatment was initially effective, keratitis recurred 10 days after its initiation. Repeated corneal scraping revealed an abundance of Gram-positive chain cocci and a small amount of fungi, resulting in the switching of an antibiotic medication from levofloxacin to moxifloxacin and cefmenoxime. Keratitis resolved gradually after the conversion. Stemphylium sp., Acremonium sp., and α-Streptococcus sp. were simultaneously isolated from the corneal scrapings. CONCLUSIONS: To the best of our knowledge, this is the first case of fungal keratitis caused by Stemphylium sp., and also the first case of super-infection in the cornea caused by two different fungi and one bacterium. Microscopic examination of the corneal scrapings was beneficial in rapid decision of changing to appropriate drug according to the dominancy of pathogenicity.

Preparation of Fine Particles with Improved Solubility Using a Complex Fluidized-Bed Granulator Equipped with a Particle-Sizing Mechanism.

A new type of fluidized-bed granulator equipped with a particle-sizing mechanism was used for the preparation of fine particles that improved the solubility of a poorly water-soluble drug substance. Cefteram pivoxyl (CEF) was selected as a model drug substance, and its solution with a hydrophilic polymer, hydroxypropyl cellulose (HPC-L), was sprayed on granulation grade lactose monohydrate (Lac). Three types of treated particles were prepared under different conditions focused on the spraying air pressure and the amount of HPC-L. When the amount of HPC-L was changed, the size of the obtained particles was similar. However, particle size distribution was dependent on the amount of HPC-L. Its distribution became more homogenous with greater amounts of HPC-L, but the particle size distribution obtained by decreasing the spraying air pressure was not acceptable. By processing CEF with HPC-L using a complex fluidized-bed granulator equipped with a particle-sizing mechanism, the dissolution ratio was elevated by approximately 40% compared to that of unprocessed CEF. Moreover, in the dissolution profile of treated CEF, the initial burst was suppressed, and nearly zero order release was observed up to approximately 60% in the dissolution profile. This technique may represent a method with which to design fine particles of approximately 100 µm in size with a narrow distribution, which can improve the solubility of a drug substance with low solubility.

In vitro assessment of the cytotoxicity of six topical antibiotics to four cultured ocular surface cell lines.

To determine the cytotoxicity of antibiotic eyedrops to ocular surface cells using a semi-quantitative method, a range of commercially available antibiotic eyedrops were assessed by using three corneal cell lines and one conjunctival cell line. All antibiotic solutions were free of benzalkonium chloride. Cell viability was determined by the MTT assay and neutral red assay following the exposure of cells to the undiluted, 2- and 10-fold diluted drugs for 10, 30, and 60 min. Toxicity was compared using % cell viability score (%CVS) . The tested eyedrops and values of %CVS50 and %CVS40/80 were Bestron(®) (cefmenoxime, 100, 94) , Panimycin(®) (dibekacin, 86, 58) , Noflo(®) (norfloxacin, 90, 50) , Cravit(®) (levofloxacin, 86, 46) , Tosfulo(®) (tosufloxacin, 57, -3) , and Vigamox(®) (moxifloxacin, 57, -6) . Cell viability markedly increased after dilution. For instance, cell viability assayed by MTT was > 80% for all the measurements in antibiotics diluted 10-fold, and the rate of the measurements showing > 80% cell viability decreased to 43% (31 out of 72 measurements) in the solutions diluted 2-fold. Of the drugs tested, Bestron(®) containing cefmenoxime showed the weakest toxicity. Vigamox(®) containing moxifloxacin and Tosuflo(®) containing tosufloxacin were more toxic when compared with the other antibiotics. CVS was useful for the comparison of the cytotoxicity of the drugs.

[Drug sensitivity of causative agents in ocular infection of external adnexa and anterior segments--multicenter study of causative agents and drug sensitivity of ocular infection by the Japanese Association for Ocular Infection part II].

PURPOSE: To report the drug sensitivity of causative agents produced by ocular infection of external adnexa and anterior segments investigated by the nationwide survey conducted by Japanese Association for Ocular Infection between September, 2007 and August, 2008. SUBJECTS AND METHODS: Among all strains isolated, causative and presumed causative agents were selected according to the criteria described, and drug sensitivity tests were conducted by minimum inhibitory concentrations (MIC) with 10 kinds of antimicrobial agents including 5 fluoroquinolones. RESULTS: Among 281 causative isolates, cefmenoxime (CMX) showed the highest sensitivity, followed by fluoroquinolones. Staphylococci and Streptococci were more sensitive to fluoroquinolones when compared to the others. Haemophilus influenzae was very sensitive to all fluoroquinolones. Corynebacterium spp. and Propionibacterium acnes were most sensitive to CMX and erythromycin respectively. CONCLUSION: CMX and fluoroquinolones showed generally good sensitivity among causative pathogens of ocular infection.

Impurity profiling of Cefteram pivoxil based on Fourier transform ion cyclotron resonance MS.

Profiling impurities for the active pharmaceutical ingredients (APIs) is an indispensable step in drug development process. Nowadays, high resolution mass spectrometry is the first choice for determining the chemical formula of organic impurities. However, merely base on the accurate mass to screen the formula is obviously not a flawless method. In this paper, a reliable strategy based on Fourier transform ion cyclotron resonance mass spectrometry (FT-ICR MS) was presented to profile the related impurities. Firstly, Cefteram pivoxil was subjected to forced degration under hydrolytic (acidic and basic), oxidative, photolytic and thermal conditions according to ICH guidelines. Then, a highly specific and efficient HPLC-FT-ICR MS compatible method was developed and it was used to separate and characterize the process related substances and the major degradation products in Cefteram pivoxil. Next, isotopic fine structures (IFSs) of all impurities were acquired to decisively determine their elemental composition. Finally, the possible chemical structures of impurities were predicted by combining the information of accurate mass, retention time, IFSs and characteristic fragmentation ions. As a result, a total of 20 related substances including 6 process related substances and 14 degradation products were identified and characterized. To the best of our knowledge, 13 of these related substances were not reported in the previous literature. It indicates that the developed strategy is accurate and standard independent to determine the chemical formulae of organic impurities in APIs. In conclusion, the impurity profiles obtained in this study are critical to the quality control and stability study of Cefteram pivoxil. Moreover, the developed method can be used as a versatile workflow to profile the impurities in APIs in the future, especially for the unknown impurities.

Consensus guidance of nebulizer therapy for acute rhinosinusitis.

The guidance deals with the recommended applications, procedures, and safety management of nebulizer therapy for acute rhinosinusitis. In Japan, nebulizer therapy for sinusitis has been covered by public health insurance since 1958 and has been commonly carried out nationwide. The Japan Society for Infection and Aerosol in Otorhinolaryngology and the Oto-Rhino-Laryngological Society of Japan set up a working group to draw up a consensus guidance on nebulizer therapy for acute rhinosinusitis. The device for nebulizer therapy are classified into jet, ultrasound, and mesh types. In Japan, cefmenoxime hydrochloride (CMX) was approved for use in nebulizer therapy since 1996. The widening of the obstructed lesions such as large polyps prior to nebulizer therapy were recommended. The numbers of times of nebulizer therapy is recommended for three times in a week for at least for 2 weeks (cure rate: 68%, eradication ratio: 48%). Concerns should be pay for the changes of activity of medicine due to the mixing and bacterial contamination. Pseudomonas cepacia growing in a short even in both saline and distilled water leads to contamination at high concentrations by 2 days. Nebulizer therapy is an effective treatment based on a drug delivery system (DDS) to the nasal and paranasal cavities. The therapy effectively increases the local drug concentration by promptly and uniformly delivering drugs to a targeted local site. The therapy is safe with less systemic absorption and with few adverse reactions.

Pharmacokinetics and bioequivalence studies of cefteram pivoxil in healthy Chinese volunteers.

A simple, sensitive and specific method has been developed for the determination of cefteram in human plasma. Sample preparation was accomplished through protein precipitation with 20% trichloroacetic acid (v/v) and chromatographic separation was performed on a C18 column at 25 degrees C. The mobile phase consisted of methanol-aqueous 20 mM ammonium acetate (18:82, v/v) at flow rate of 1.0 mL/min. Wavelength was set at 235 nm. The lower limit of quantification was 0.04 microg/mL and the assay exhibited a linear range of 0.04-3.2 microg/mL (r=0.9996). The relative recoveries of cefteram from human plasma at three different concentrations were more than 90%. The method was successfully applied to investigate the bioequivalence between two kinds of cefteram pivoxil preparations (test vs reference) in 24 healthy Chinese volunteers. After a single 100 mg dose for the test and reference product, the resulting means of major pharmacokinetic parameters such as AUC(0-t), AUC(0-infinity), Cmax and Tmax of cefteram pivoxil were 4.75 +/- 1.35 vs 4.76 +/- 1.29 microg h/mL, 4.89 +/- 1.36 vs 4.91 +/- 1.29 microg h/mL, 1.65 +/- 0.45 vs 1.73 +/- 0.45 microg/mL and 1.48 +/- 0.59 vs 1.73 +/- 0.45 h, respectively, indicating that these two kinds of preparations were bioequivalent.

[Evaluation of antimicrobial prophylaxis after normal delivery].

In Japan, as a measure to prevent puerperal infection, oral antimicrobial prophylaxis has been conducted after delivery in many maternity clinics. However, there are only a few reports on the evidence supporting the validity of antimicrobial prophylaxis following normal delivery. There is concern that unnecessary antimicrobial administration may be conducted in such clinics. In the present study, the puerperal females after normal delivery were placed on different treatments. A group of females received no oral antimicrobial administration. The remaining females were given cefteram pivoxil (CFTM-PI) in the two different doses. In this manner, we evaluated usefulness of antimicrobial prophylaxis. We compared three treatment groups with respect to the incidence of infection for the period until the first week after discharge, and obtained the following results: non-antimicrobial prophylaxis group (group A), 5.83%; antimicrobial prophylaxis group (group B), 1.77%; antimicrobial prophylaxis group (group C), 0%. In group B, the puerperal females were orally given CFTM-PI in a total daily dose of 300 mg, three times daily for three days. In group C, the puerperal females were orally given CFTM-PI in a total daily dose of 300 mg, three times daily for five days. The incidence of infection was the lowest in group C which was followed by group B and group A in this order and the significant intergroup difference was recognized (p=0.004). We also compared the total counts of bacteria, aerobes and anaerobes in lochia on the fifth day during the puerperal period with those on the first day in each treatment group. The decrease in bacterial count was the largest in group C, which was followed by group B and group A in this order. Compared with the total bacterial counts obtained on the first day, those obtained on the fifth day decreased significantly (p<0.001). The results of the present study showed usefulness of antimicrobial prophylaxis after normal delivery. As one of the factors, a significant decrease in the count of bacteria in lochia seems to contribute toward producing the satisfactory outcome.

Pharmacokinetic and bioequivalence comparison of a single 100-mg dose of cefteram pivoxil powder suspension and tablet formulations: a randomized-sequence, open-label, two-period crossover study in healthy Chinese adult male volunteers.

BACKGROUND: Cefteram pivoxil (CFTM-PI) is an oral antibiotic available in powder suspension and tablet formulations indicated in China for the treatment of bacterial infections. Although these 2 formulations are marketed in China, published information regarding their pharmacokinetics and bioequivalence in the Chinese population is not available. OBJECTIVE: The aim of this study was to compare the pharmacokinetics and bioequivalence of the powder suspension (test) and tablet (reference) formulations of CFTM-PI 100 mg available in China. METHODS: This single-dose, randomized-sequence, open-label, 2-period crossover study was performed at the Nanjing First Hospital of Nanjing Medical University. Eligible subjects were healthy male volunteers who were randomly assigned at a 1:1 ratio to receive a single 100-mg dose of the test or reference formulation, followed by a 1-week washout period and administration of the alternate formulation. The study drugs were administered after a 12-hour overnight fast. Plasma was assayed using a high-performance liquid chromatography method. For analysis of pharmacokinetic properties, including C(max), AUC from time 0 (baseline) to 6 hours (AUC(0-6)), and AUC from baseline to infinity (AUC(0-infinity)), blood samples were obtained at intervals over the 6-hour period after study drug administration. The formulations were considered bioequivalent if the log-transformed ratios of C(max) and AUC were within the predetermined equivalence range (80%-125%) as established by the US Food and Drug Administration (FDA). Tolerability was assessed by monitoring vital signs and laboratory tests (hematology, blood biochemistry, hepatic function, and urinalysis), and by questioning subjects about adverse events (AEs). RESULTS: Twenty-four Chinese male subjects (mean [range] age,24.2 [23-32] years;weight,64.3 [58-67] kg; height, 172 [167-185] cm) enrolled; all completed the study. No period or sequence effect was observed. The 90% CIs for the log-transformed ratios of C(max), AUC(0-6;), and AUC(0-infinity) were 96.5 to 120.1, 95.7 to 110.2, and 96.2 to 110.4, respectively (all, P>0.05). Similar results were found for the data without log-transformation. No AEs occurred or were reported during the study. CONCLUSIONS: In this small study in healthy Chinese adult male volunteers, a single 100-mg dose of the powder-suspension formulation was bioequivalent to a single 100-mg dose of the tablet formulation based on the US FDA's regulatory definition (rate and extent of absorption). Both formulations were well tolerated.

Ceftezole, a cephem antibiotic, is an alpha-glucosidase inhibitor with in vivo anti-diabetic activity.

Using a high throughput-compatible assay to screen for potential alpha-glucosidase inhibitors, we found that the beta-lactam antibiotic ceftezole exhibited potent alpha-glucosidase inhibitory activity. In in vitro alpha-glucosidase assays, ceftezole was shown to be a reversible, non-competitive inhibitor of yeast alpha-glucosidase with a Ki value of 5.78 x 10(-7) M when the enzyme mixture was pretreated with ceftezole. Using an in vivo streptozotocin-induced mouse model, we confirmed that blood glucose levels decreased by 30% 20 min after ceftezole treatment (10 mg/kg/day). Expression levels of glycogen synthase kinase-3, peroxisome proliferator-activated receptor-gamma, and uncoupling protein-3 mRNA were also slightly decreased compared to controls following ceftezole treatment. Taken together, these in vivo and in vitro results suggest that ceftezole may be a clinically useful anti-diabetic compound.

[The effect of preoperative topical antibiotics in cataract surgery].

PURPOSE: We studied whether topical antibiotics prevent endophthalmitis after cataract surgery. METHODS: Cefmenoxime hydrochloride (CMX) or artificial tears (AT) were randomly instilled 72 hours before surgery. Conjunctival swab samples were taken before the instillation of eye drops (1) and after the instillation of eye drops (2). Aqueous humor (3) was cultured intraoperatively. RESULTS: Positive cultures were found in the CMX group of eyes in 76.3% of (1) samples, 58.1% of (2) samples, and 6.0% of (3) samples. In the AT group of eyes, positive cultures were found in 78.6% of (1) samples, 63.8% of (2) samples, and 2.9% of (3) samples. CMX was not effective. In the CMX group of eyes, Staphylococcus epidermidis was found in 59 eyes of group (1), 5 eyes of group (2), and 0 eyes of group (3). In the AT group of eyes, S. epidermidis was found in 70 eyes of group (1), 26 eyes of group (2), and 1 eye of group (3). In the cases where S. epidermidis was decreased by CMX topical use Propionibacterium acnes was increased. CONCLUSIONS: There is a possibility that preoperative topical use of CMX can reduce S. epidermidis. On the other hand, it might increase P. acnes. Considering these results and the fact that there was no difference in effectiveness in the aqueous humor cultures, preoperative CMX topical use may not prevent postoperative endophthalmitis except for endophthalmitis due to S. epidermidis.

Characteristics of Pseudomonas corneal infection related to orthokeratology.

PURPOSE: To describe a Pseudomonas aeruginosa corneal infection resulting from orthokeratology. METHODS: Case report. RESULTS: A 17-year-old boy wearing orthokeratology (OK) lenses was referred to our clinic because of redness in his right eye in spite of his usage of ofloxacin (OFLX) eye drops. An excavated paracentral corneal ulcer with an immune ring and hypopyon was observed. It was positioned under the paracentral steeper portion of the optic of the OK lens. Culture of the lens solution revealed P. aeruginosa. The patient was treated with topical OFLX and cefmenoxime (CMX) plus intravenous and subconjunctival injections of cefozopran (CZOP), successfully. The antibiotic susceptibility of P. aeruginosa by the disk diffusion susceptibility test was reduced under moderately hypoxic conditions. Glycocalyx slime was formed on the OK lens in vitro by P. aeruginosa isolated from the case. CONCLUSIONS: Changes in P. aeruginosa susceptibility to antibiotics under moderately hypoxic conditions and glycocalyx slime formation might affect the features of OK lens-associated infections.

Clinical Characteristics and Bacteriological Profile of Moraxella Keratitis.

PURPOSE: Moraxella species are rare causative pathogens of severe sight-threatening keratitis. The aim of this study was to analyze the clinical presentation, predisposing risk factors, in vitro antimicrobial susceptibility, and treatment associated with Moraxella keratitis. METHODS: We retrospectively reviewed 30 culture-proven cases of Moraxella keratitis from multiple centers in Japan. RESULTS: The mean age of the patients was 58.4 ± 23.4 years. The most common ocular conditions were contact lens wearing (5 patients, 16.7%) and trauma (3 patients, 10.0%). Seven patients had diabetes mellitus. Sixteen patients exhibited hypopyon in association with the corneal focus. Ring-shaped infiltration was found in 9 patients (30.0%), and irregular or amoebic-shaped infiltration was observed in 13 patients (43.3%). Eight patients (26.7%) showed small round infiltrates. All Moraxella isolates were sensitive to fluoroquinolones and aminoglycosides. All were treated with a combination ophthalmic solution containing a fluoroquinolone, tobramycin, and cefmenoxime. Although no patients developed corneal perforation, the response to treatment was slow in all cases; the mean treatment period was 41.9 days. CONCLUSIONS: In Japan, Moraxella keratitis occurs in patients with contact lens wear, trauma, and diabetes mellitus. It presents as a small, round, ring-shaped, irregularly shaped, or amoebic-shaped focus. Moraxella species exhibit good susceptibility to fluoroquinolones and aminoglycosides. Because the treatment response may be very slow, these agents should be continued for a long period of time.

Effect of protein binding on cefmenoxime steady-state kinetics in critical patients.

The effect of protein binding on cefmenoxime steady-state kinetics was studied in 20 critical patients with gram-negative pneumonia. Sixteen patients were given 1 gm cefmenoxime every 6 hr, two received 2 gm every 6 hr, and two received 2 gm every 8 hr. Serum protein binding was measured by equilibrium dialysis. Assays were by HPLC. Serum cefmenoxime concentration-time data were characterized by a model-independent method based on statistical moment theory. Despite varying renal function in patients, mean cefmenoxime serum concentration-time curves for all three dosing regimens were closely aligned, reflecting successful empiric dosage adjustment. Terminal phase t 1/2 ranged from 0.8 to 2.9 hr and was significantly related to creatinine clearance. Cefmenoxime total clearance was significantly related to both lambda z (2.303 times the slope of the terminal portion of the log-concentration-time curve) and creatinine clearance (CCr). Plasma clearance of free cefmenoxime was more strongly correlated with CCr than the clearance of total cefmenoxime. Drug recovery from 24-hr urine collections at steady state was 76.9 +/- 19.8% of the daily dose (mean +/- SD, n = 13). Cefmenoxime protein binding in patients differed markedly from normal values. A regression equation derived from data on 11 cephalosporins appeared to predict total volume of distribution in the steady state (Vdss-Total) from the fraction of unbound drug accurately. Since cefmenoxime has a high therapeutic index, no clinical consequences are expected to result from variation in protein binding. Observed differences in protein binding between patients and normal subjects could have clinical consequences for highly bound acidic drugs that, unlike cefmenoxime, have narrow therapeutic indices.

Cefmenoxime: in vitro activity.

The in vitro activity of cefmenoxime (SCE-1365 or A-50912), a new semisynthetic cephalosporin antibiotic, was determined for a broad spectrum of 1,234 organisms isolated as part of a multiclinic study. The minimum inhibitory concentration (MIC) of cefmenoxime required to inhibit at least 90 percent of strains tested (MIC90) ranged from 0.12 to 8 micrograms/ml for Enterobacteriaceae. MIC90S were 0.015 and 0.06 microgram/ml for Streptococcus pneumoniae and S. pyogenes, respectively, and 4 micrograms/ml for Staphylococcus aureus. Group D streptococci were less susceptible. The MIC90 of cefmenoxime for Neisseria gonorrhoeae and Hemophilus influenzae was 0.06 microgram/ml. Cefmenoxime was less active against Pseudomonas aeruginosa, Acinetobacter species, and Bacteroides fragilis (MIC50 = 16 micrograms/ml).

Clinical results and concentrations of cefmenoxime in serum, amniotic fluid, mother's milk, and umbilical cord.

Cefmenoxime administered intravenously was used to treat a variety of gynecologic and obstetric infections in 40 patients. Many were mixed infections. The mean age of the patients was 39.7 +/- 2.39 years. The dosage of cefmenoxime was 2 g per day (n = 30) or 1 g per day (n = 10). Cefmenoxime levels were assayed microbiologically in serum, milk, amniotic fluid, and placental tissues. The overall bacteriologic cure rate was 86 percent. Clinically, 100 percent of the patients were treated successfully. Side effects were generally mild, and in no case was treatment discontinued. Twelve hours after the last bolus injection, levels of cefmenoxime were 1.1 microgram/ml in serum and 1.75 microgram/ml in milk. Thirty minutes after a 1 g bolus injection in patients undergoing cesarean section, mean maternal serum concentrations were 33 micrograms/ml. Concentrations were 7.4 micrograms/ml in umbilical cord blood and 2.3 micrograms/ml in amniotic fluid.

Affinity of cefmenoxime for beta-lactamases: an analysis.

The interactions of cefmenoxime with beta-lactamases in comparison with cefotaxime, moxalactam, cefoperazone, and ceftazidime have been determined. On-line computerized microacidimetry allowed determination of the affinity of these compounds with the enzymes, which was characterized by Km values. The beta-lactamases that were used were two cephalosporinases and one penicillinase. Within these data, the cephalosporins could be classified into three groups: (1) those with high affinity for the cephalosporinases and very poor affinity for the penicillinase (cefmenoxime, cefotaxime, and moxalactam); (2) those with moderate affinity for the cephalosporinases and very poor affinity for the penicillinase (ceftazidime); (3) those with poor affinity for all enzymes (cefoperazone). In the case of the penicillinase (TEM-1), only cefoperazone was subject to some hydrolysis.

Pharmacokinetic study of cefmenoxime (SCE 1365-CMX) in healthy adults.

Cefmenoxime pharmacokinetics were investigated in six healthy volunteers after intravenous and intramuscular administration of 0.5, 1, and 2 g. Blood and urine samples were analyzed by reversed-phase high-pressure liquid chromatography using ultraviolet detection at 275 nm. The assay is precise and linear up to 200 micrograms/ml-1, with 0.02 micrograms/ml-1 as the limit of detection. Linearity of cefmenoxime kinetics was demonstrated because the area under the plasma concentrations is proportional to studied doses. Eight hours after 1 g of cefmenoxime intramuscularly, mean plasma concentrations are, respectively, 0.6 +/- 0.1 and 0.3 +/- 0.1 microgram/ml-1. Intramuscular cefmenoxime is rapidly absorbed (Ka = 7.28 hours-1) with complete bioavailability (F = 0.99); apparent volume of distribution is 0.35 liters/kg-1 and elimination half-life 1.5 hours. The fraction of cefmenoxime excreted unchanged in the urine after intramuscular administration is 0.72, indicating a major contribution of renal clearance in total clearance. Experimental data after intramuscular administration were well fitted with a two-compartment model.

Cefmenoxime therapy in bacterial osteomyelitis.

Cefmenoxime, a new parenteral beta-lactamase-resistant cephalosporin, was evaluated for safety and efficacy in 15 patients (10 male and five female) with acute (1 patient) and chronic (14 patients) osteomyelitis. Diagnosis was made by culture of the surgical biopsy specimen. Osteomyelitis was treated with 8 to 12 g of cefmenoxime per day (mean 9.1 g) for 42 to 66 days (mean 47.3). Staphylococcus aureus was the most frequently isolated organism. Minimum inhibitory concentrations (MICs) of cefmenoxime were determined and all pathogens were inhibited by 12.5 micrograms/ml or less, except for Enterobacter cloacae and Acinetobacter species, both of which had an MIC of 25.0 micrograms/ml. All patients had at least one surgical debridement. Of the 15 patients, 10 (67 percent) had the osteomyelitis "arrested." These patients have been followed up five to 14 months after completion of cefmenoxime therapy. Toxicity studies indicated mild elevations in serum glutamic oxalacetic transaminase and serum glutamic pyruvic transaminase in two patients. Cefmenoxime appears to be a safe and effective antibiotic in the treatment of osteomyelitis.