Flomoxef Research Articles

Pharmacokinetic and Pharmacodynamic Analysis of the Oxacephem Antibiotic Flomoxef against Extended-Spectrum β-Lactamase-Producing Enterobacterales from Dogs.

Flomoxef (FMX) may be a potential alternative to carbapenems for dogs infected with Enterobacterales-producing extended-spectrum β-lactamase (ESBL-E). However, the appropriate dosage of FMX in dogs with ESBL-E infections has yet to be established. This study was carried out to establish appropriate treatment regimens for FMX against ESBL-E infections in dogs using a pharmacokinetics-pharmacodynamics (PK-PD) approach. Five dogs were intravenously administered at a bolus dose of FMX (40 mg/kg body weight). Serum concentrations of FMX were calculated with high-performance liquid chromatography-tandem mass spectrometry, and then applied to determine PK indices based on a non-compartmental model. The cumulative fraction of response (CFR) was estimated based on the dissemination of minimum inhibitory concentrations among wild-type ESBL-E from companion animals. From the results, the dosage regimens of 40 mg/kg every 6 and 8 h were estimated to attain a CFR of >90% for wild-type isolates of ESBL-producing Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis for dogs. By contrast, all regimens had a CFR of <80% for ESBL-producing Enterobacter cloacae. Our results indicated that dosage regimens of 40 mg/kg FMX every 6 and 8 h can be a non-carbapenem treatment for canine infections of ESBL-producing Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, but not for those of ESBL-producing Enterobacter cloacae.

The Genotypic and Phenotypic Characteristics Contributing to Flomoxef Sensitivity in Clinical Isolates of ESBL-Producing E. coli Strains from Urinary Tract Infections.

We carried out a molecular biological analysis of extended-spectrum β-lactamase (ESBL)-producing E. coli strains and their sensitivity to flomoxef (FMOX). Sequence type (ST) analysis by multilocus sequence typing (MLST) and classification of ESBL genotypes by multiplex PCR were performed on ESBL-producing E. coli strains isolated from urine samples collected from patients treated at our institution between 2008 and 2018. These sequences were compared with results for antimicrobial drug susceptibility determined using a micro-liquid dilution method. We also analyzed cases treated with FMOX at our institution to examine its clinical efficacy. Of the 911 E. coli strains identified, 158 (17.3%) were ESBL-producing. Of these, 67.7% (107/158) were strain ST-131 in ST analysis. Nearly all (154/158; 97.5%) were CTX-M genotypes, with M-14 and M-27 predominating. The isolated strains were sensitive to FMOX in drug susceptibility tests. Among the patient samples, 33 cases received FMOX, and of these, 5 had ESBL-producing E. coli. Among these five cases, three received FMOX for surgical prophylaxis as urinary carriers of ESBL-producing E. coli, and postoperative infections were prevented in all three patients. The other two patients received FMOX treatment for urinary tract infections. FMOX treatment was successful for one, and the other was switched to carbapenem. Our results suggest that FMOX has efficacy for perioperative prophylactic administration in urologic surgery involving carriers of ESBL-producing bacteria and for therapeutic administration for urinary tract infections. Use of FMOX avoids over-reliance on carbapenems or β-lactamase inhibitors and thus is an effective antimicrobial countermeasure.

Differences in clinical and cost-effectiveness between cefmetazole and flomoxef for the prevention of surgical site infection in elective colorectal surgery: A single-center, retrospective cohort study

IntroductionSurgical site infection (SSI) is associated with increased morbidity and mortality rates, postoperative length of stay (pLOS), and medical costs. In colorectal surgery, cefmetazole (CMZ) and flomoxef (FMOX) are predominantly used in Japan, and they have almost the same spectrum of antibiotic activity against SSI pathogens, and an approximately four-fold cost difference (CMZ: ∼4$, FMOX: ∼16$). However, the difference between these antibiotics in SSI prophylaxis in colorectal surgery remains poorly understood. MethodsWe performed a single-center retrospective cohort study to investigate the prophylactic effects of these antibiotics, pLOS, and hospitalization costs. Patients who underwent elective colorectal surgery between April 2016 and March 2020 were considered for this study. ResultsOf the 634 patients, 316 (49.8%) were eligible. The SSI rates in the CMZ and FMOX groups were 14.7% and 12.5%, respectively. The incidence of organ/space SSI was approximately two-fold lower in the CMZ group than in the FMOX group (4.4% vs. 9.4%). Multivariable regression analysis revealed that CMZ was not significantly related to SSI, with an adjusted odds ratio of 1.21 (95% confidence interval [CI]: 0.52–2.82) and did not induce a significant difference in pLOS (difference ratio: 0.951 [95% CI: 0.868–1.041]). Hospitalization costs were reduced in the CMZ group (difference ratio, 0.951 [95% CI: 0.907–0.998], p = 0.042). The sensitivity analysis also showed results similar to the above findings. ConclusionOur study showed that CMZ could be a cost-effective antibiotic with similar efficacy for SSI prophylaxis in colorectal surgery, compared with FMOX.

Pharmacokinetics/Pharmacodynamics Evaluation of Flomoxef against Extended-Spectrum Beta-Lactamase-Producing Escherichia coli In Vitro and In Vivo in a Murine Thigh Infection Model.

Although flomoxef (FMOX) has attracted substantial attention as an antibiotic against extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-producing E. coli), the pharmacokinetics/pharmacodynamics (PK/PD) characteristics of FMOX against ESBL-producing E. coli is unclear. The aim of this study was to determine the PK/PD index of FMOX against ESBL-producing E. coli. In vitro time-kill curve studies and in vivo PK/PD experiments were carried out. Time-kill curves exhibited a unique bactericidal activity: time-dependent activity at low concentrations and concentration-dependent activity at high concentrations. In neutropenic murine thigh infection experiments, the antibacterial activity of FMOX correlated with the time that the free drug concentration remaining above the minimum inhibitory concentration (MIC) (fT>MIC) and the ratio of the area under the free drug concentration-time curve for a 24h period to the MIC (fAUC24/MIC). However, the burden of ESBL producing E. coli significantly reduced when the time intervals for administration were shorter among three dosage regimens with same magnitude of fAUC24/MIC, indicating that fT>MIC is significant PK/PD index. The target value of fT>MIC for 1 log10 kill reduction was 35.1%. fT>MIC is the most significant PK/PD index of FMOX against ESBL-producing E. coli and its target value is ≥ 40%.

Change in the Antimicrobial Resistance Profile of Extended-Spectrum β-Lactamase-Producing Escherichia coli.

BackgroundThis study aimed to investigate the trends and antimicrobial resistance profile of extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) clinical isolates.MethodsA total of 1,303 E. coli isolates from January 2012 to December 2017 at Fukuoka University Chikushi Hospital, Japan, were analyzed. The rate of resistance to cefmetazole (CMZ), flomoxef (FMOX), imipenem (IPM), meropenem (MEPM), amikacin (AMK), gentamicin (GM), minocycline (MINO), ciprofloxacin (CPFX), and levofloxacin (LVFX) was compared between non-ESBL-producing E. coli (non-ESBL-EC) and ESBL-EC.ResultsThe proportion of ESBL-EC among all the E. coli isolates was 24.6% (320/1,303), and the proportion remained stable throughout the study period. There was no difference in the rate of resistance to CMZ, FMOX, IPM, MEPM, and AMK between non-ESBL-EC and ESBL-EC; however, the rate of resistance to GM, MINO, CPFX, and LVFX was higher in ESBL-EC than in non-ESBL-EC (17.5% vs. 10.0%, 19.1% vs. 7.7%, 87.5% vs. 24.2%, and 87.5% vs. 23.5%, respectively; P < 0.01). The rate of resistance to CPFX and LVFX in ESBL-EC increased throughout the study course. The rate of E. coli isolates susceptible to all the antibiotics was significantly higher in non-ESBL-EC than in ESBL-EC (68.2% vs. 7.5%; P < 0.01), and this rate decreased significantly from 10.0% in 2012 to 3.8% in 2017 in ESBL-EC (P < 0.01).ConclusionsOur findings indicate a changing antimicrobial resistance profile of ESBL-EC, particularly to fluoroquinolones. Determination of the prevalence and antimicrobial resistance of ESBL-EC will help physicians in selecting the initial empirical treatment for patients with ESBL-EC infections.

Efficacy of non-carbapenem antibiotics for pediatric patients with first febrile urinary tract infection due to extended-spectrum beta-lactamase-producing Escherichia coli.

Although carbapenem is the recommended for urinary tract infection (UTI) caused by extended-spectrum beta-lactamase (ESBL)-producing organisms, non-carbapenems have been reported to be effective for adult patients with UTI caused by ESBL-producing organisms. The purpose of this study was to evaluate the efficacy of non-carbapenems for pediatric patients with UTI due to ESBL-producing Escherichia coli (E.coli) based on the microbiologic and clinical outcomes. Fifteen children, who were treated for first febrile UTI caused by ESBL-producing E.coli were enrolled in this study. Antimicrobial susceptibilities and ESBL production were determined according to the Clinical and Laboratory Standards Institute guidelines. To detect CTX-M genes, polymerase chain reaction was performed with specific primers for blaCTX-M detection. Of the 15 enrolled patients, 10 (66.7%) were boys and 5 (33.3%) were girls, with a median age of four months. VUR was detected in six patients (40%). For detection of blaCTX-M by PCR, CTX-M-3, CTX-M-8, CTX-M-14, and CTX-M-15 were detected in five, one, eight, and one patient, respectively. Overall, 14 of the 15 isolates (93.3%) were susceptible for fosfomycin (FOM), and all isolates were susceptible for cefmetazole (CMZ), flomoxef (FMOX), and imipenem/cilastatin (IPM/CS). Of the 15 patients, 12 (80%) clinically improved without the use of carbapenems. In conclusion, even if isolates of ESBL-producing E.coli are multidrug resistant based on MIC assessment, clinical susceptibility to non-carbapenems, such as CMZ, FMOX, and FOM, is possible. Accordingly, carbapenems may not be required all the time for treatment of pediatric UTI in clinical practice.

Pelvic peritonitis during biologic therapy for rheumatoid arthritis: a case report and review of the literature.

IntroductionInfections are recognized as major complications during therapy with biologics and other immunosuppressant drugs. The respiratory tract, bone, joint, skin, and soft tissues are well known sites of infection in patients with rheumatoid arthritis (RA) treated by biologics or other immunosuppressants. It is known that patients with intra-abdominal infections may develop tuberculous peritonitis during biologic therapy. However, non-tuberculous pelvic peritonitis is rare.Case descriptionA case of a 46-year-old patient with RA developed pelvic peritonitis during therapy with MTX, tacrolimus (TAC), and golimumab (GLM). The patient visited our hospital due to a fever and general malaise. Physical findings included lower abdominal tenderness and rebound tenderness. Abdominal computed tomography (CT) images showed an intrauterine foreign body and ascites. The contraceptive ring was removed. Streptococcus agalactiae and Streptococcus constellatus were cultured from the removed contraceptive ring. She was started on an antimicrobial agent, flomoxef (FMOX), at 2 g/day. The FMOX dosage was increased to 3 g/day from the 3rd day of disease and continued for 10 days. Her fever disappeared from the 4th disease day, and her inflammatory response then gradually decreased. No exacerbation of symptoms occurred even after the FMOX treatment was stopped, and the patient was discharged on the 14th disease day.Discussion and evaluationMTX and biologics were being administered at the time of onset of peritonitis. The peritonitis was diagnosed on the basis of the gynecological evaluation and CT imaging findings that were typical of peritonitis. The patient was in an immunosuppressed state during administration of anti-rheumatic drugs, and the peritonitis was thought to have developed due to an ascending infection via the long-term presence of the intrauterine contraceptive ring which had an attached string.ConclusionsBefore starting biological agents, patients must be questioned regarding the presence of an intrauterine foreign body.

Flomoxef in neonates and young infants; clinical efficacy, pharmacokinetic evaluation and effect on the intestinal bacterial flora

Forty-three newborn and young infants including 13 low-birth-weight (LBW) infants were treated with flomoxef (FMOX) and the clinical efficacy and side effect were evaluated. The ages of the patients ranged from 0 to 99 days, and their body weights from 797 to 9,000 g. Dose levels were 10.5 to 48.5 mg/kg every 6 to 8 hours for 3 to 12 days. Those patients who responded to the FMOX treatment included 8 infants with sepsis, 14 with suspected sepsis, 6 with intrauterine infection, 2 with meningitis, 7 with pneumonia, 1 with staphylococcal scalded skin syndrome, 1 with epididymitis and 4 with urinary tract infections. The results were excellent in 17 and good in 22 patients. The drug was well tolerated, although diarrhea occurred in 2, slightly elevated serum concentrations of transaminases in 2, and eosinophilia and thrombocytosis in 1 patient each. Pharmacokinetic studies on FMOX with 20 mg/kg dose were done in 19 patients including 8 LBW infants. Serum concentrations at 15 minutes after intravenous bolus injection in five 1- to 6-day-old LBW, five 1- to 6-day-old and four 8- to 19-day-old mature infants were 52.6, 52.7 and 58.0 micrograms/ml, respectively, and those at 4 hours were 22.1, 13.3 and 5.2 micrograms/ml, respectively. Serum half-lives of the drug were 3.93, 2.29 and 1.62 hours, respectively, and excretion rates of this drug into urine in the first 6 hours after administration were 30.4, 45.1 and 58.7%, respectively. Mean serum concentrations just after intravenous 1-hour drip infusion in three 8- to 54-day-old LBW and two 8- and 10-day-old mature infants, were 31.5 and 18.9 micrograms/ml, respectively, and those at 4 hours were 15.3 and 4.3 micrograms/ml, respectively. Serum half-lives of the drug were 2.88 and 1.75 hours, respectively, and excretion rates of the drug into urine in the first 6 hours were 22.6 and 47.5%, respectively. The cerebrospinal fluid level at 3 hours after a dose was 7.09 micrograms/ml on the second day of treatment in a patient with Staphylococcus aureus meningitis receiving 50 mg/kg of the drug every 6 hours per day. Its level at 1 hour after a dose was 3.52 micrograms/ml on the 8th day of treatment in the same patient. The influence of FMOX on the fecal flora was studied in 7 patients. The characteristic pattern observed during the drug administration was the disappearance of Bifidobacterium, the decrease or disappearance of Enterobacteriaceae and the preservation of Streptococcus.(ABSTRACT TRUNCATED AT 250 WORDS)

Laboratory and clinical studies on flomoxef in neonates and premature infants

Flomoxef (FMOX), an oxacephem antibiotic of beta-lactam antibiotic family, was administered to 16 infants including 6 neonates and 10 premature infants at a dose of 20 or 40 mg/kg via intravenous injection, and plasma and urinary concentrations and the urinary recovery were determined. In addition, FMOX was administered via intravenous injection at daily doses averaging 85.5 mg/kg divided into 2 to 4 times for durations averaging 9 days to 96 infants from 0- to 90-day old (mainly neonates and premature infants). In 44 of the 96 infants with bacterial infections, clinical and bacteriological efficacies were evaluated, and prophylactic effects of FMOX were determined in the remaining 52 infants. Adverse reaction and laboratory tests abnormalities were evaluated also. The obtained results are summarized as follows. 1. Upon administration of FMOX at 20 or 40 mg/kg to neonates and premature infants via intravenous injection, plasma concentrations, half-lives and AUC were determined. In 3 neonates of 5, 7 and 16 days of ages administered with 20 mg/kg of FMOX, peak plasma concentrations of 62.5 to 99.7 micrograms/ml were achieved in 5 or 15 minutes after injection. Half-lives of FMOX in these neonates were 1.48 to 1.78 hours and AUC's were 112 to 161 micrograms.hr/ml. The same dose (20 mg/kg) of FMOX was administered to 3 premature infants of 5- 16- and 19-day of ages and initial blood samples were obtained at 5 minutes after injection from the 5-day old subject and at 15 minutes after injection from the 16-and 19-day old subjects. Peak plasma concentrations of 63.6 to 79.9 micrograms/ml were observed in the samples. Half-lives were 1.69 to 2.20 hours and AUC's were 174 to 201 micrograms.hr/ml. When 3 neonates (one 17-day old and two 24-day old subjects) were administered with 40 mg/kg of FMOX, peak plasma concentrations obtained at 5 minutes after injection were 99.7 to 122.0 micrograms/ml. Half-lives were 1.28 to 1.92 hours and AUC's were 170 to 357 micrograms.hr/ml.(ABSTRACT TRUNCATED AT 400 WORDS)

耳鼻咽喉科領域感染症におけるFlomoxef (6315-S) の基礎的,臨床的検討

耳鼻咽喉科領域感染症におけるFlomoxef (6315-S) の基礎的,臨床的検討

Clinical Characteristics and Outcome of Chryseobacterium indologenes Bacteremia

Background: Chryseobacterium indologenes, although widely distributed in nature, is a rare human pathogen. This study aims to analyze the clinical characteristics, risk factors, and outcome of patients with C. indologenes bacteremia. Methods: A retrospective study was conducted from January 1, 2002 to April 30, 2011 analyzing patients with C. indologenes bacteremia at a medical center in northern Taiwan. Results: Forty-eight episodes of C. indologenes bacteremia in 47 patients were identifi ed. Among all bacteremic episodes, 44 (92%) were nosocomial, three (6%) were healthcare-associated, and only one (2%) was community-acquired. Thirty-three episodes (69%) were primary bacteremia, and nine (19%) were from pneumonia. Forty-one isolates (85%) were non-susceptible to imipenem, and only 20% (3/15) were non-susceptible to fl omoxef. Patients with tunneled catheter, delayed onset of bacteremia, isolates were non-susceptible to ceftazidime or cefepime and potentially associated with higher mortality. Pneumonia (OR = 31.359; 95% CI = 1.35-729.39; p = 0.032) and non-susceptibility to ceftazidime (OR = 21.057; 95% CI = 2.28-194.57; p = 0.007) were independent risk factors for in-hospital mortality. Conclusions: The emergence of C. indologenes bacteremia has had a great clinical impact on inpatient care. It is important to identify the clinical characteristics of C. indologenes bacteremia and initial prompt antimicrobial treatments.

Post-operative infection and prophylactic antibiotic administration after radical cystectomy with orthotopic neobladder urinary diversion

The purpose of this study was to investigate the association between prophylactic antibiotic administration (PAA) and post-operative infection in radical cystectomy with orthotopic neobladder urinary diversion carried out for patients with bladder cancer. Fifty-seven consecutive cases were analyzed retrospectively. Post-operative infections were categorized as urinary tract, wound, and remote infections. We used the antibiotics tazobactam/piperacillin (TAZ/PIPC), sulbactam/ampicillin (SBT/ABPC), flomoxef (FMOX), cefazolin (CEZ), cefotiam (CTM), and cefmetazole (CMZ). Twenty-five (43.9%) patients had post-operative infections. Five of these (8.77%) patients had wound infections, 22 (38.6%) patients had urinary tract infections, and 2 (3.51%) had remote infections. Our statistical analysis demonstrated that the patients with TAZ/PIPC used for PAA (5/18: 27.8%) had a significantly lower post-operative infection rate than patients with other antibiotics (24/39: 61.5%) (p = 0.0442). In addition, the patients with a shorter-duration PAA (within 72 h after the operation (48-72 h)) had a significantly lower rate of post-operative infections (12/33: 36.4%) than those with longer-duration PAA (longer than 72-96 h after the operation) (16/24: 66.7%) (p = 0.0239). Taken together, these results suggest that TAZ/PIPC with shorter PAA duration (within 72 h) might lead to a lower rate of post-operative infections. In conclusion, our data showed that PAA with TAZ/PIPC with a shorter duration PAA (within 72 h) might be recommended for radical cystectomy with orthotopic neobladder reconstruction. A prospective study based on our data is desirable to establish or revise guidelines for prophylactic medication for preventing post-operative infection after radical cystectomy with orthotopic neobladder urinary diversion.

Pharmacokinetic study on distribution of Flomoxef (FMOX) to oral tissues

Pharmacokinetic study on distribution of Flomoxef (FMOX) to oral tissues

A randomized prospective study of oral levofloxacin vs intravenous flomoxef prophylaxis in postoperative infection after endoscopic sinus surgery

Objective The clinical efficacy and cost effectiveness of oral antimicrobial prophylaxis with levofloxacin (LVFX) on endoscopic sinus surgery (ESS) was evaluated. Materials and methods Ninety-three patients undergoing ESS were prospectively enrolled in the present study. The patients were randomly divided into 2 groups, LVFX and flomoxef (FMOX). Two hundred milligrams of LVFX was orally given 2 hours before the start of surgery and 6 hours after the end of surgery, which was followed by the administration of 200 mg every 12 hours for 2 days. One gram of FMOX was dissolved in 100 ml of physiological saline and given intravenously at the induction of anesthesia and 6 hours after the end of surgery, followed by infusion twice daily for 2 days. Results There were no statistically significant differences between 2 groups in terms of age, sex, systemic complications, surgical procedures, the duration of the operation, the length of hospitalization, the amount of blood loss, body temperature, or the number of white blood cells or C-reactive protein. Although no statistical significance was observed in the bacterial resistance between the two antibiotics, LVFX seems to show a low rate of resistance pattern change as compared to FMOX. The present study demonstrated that no patients treated with LVFX or FMOX were afflicted with postsurgical infection. Conclusion Oral administration of LVFX is a simple, cost-effective and safe alternative to intravenous prophylaxis in ESS based on clinical efficacy and bacteriological study.

Development of breakpoints of cephems for intraabdominal infections based on pharmacokinetics and pharmacodynamics in the peritoneal fluid of patients

We developed breakpoints for cephem antibacterial agents for intraabdominal infections based on pharmacokinetics (PK) and pharmacodynamics (PD) at the target site. Cefepime (CFPM), cefotiam (CTM), cefozopran (CZOP), and flomoxef (FMOX) were each administered to 8-10 patients before abdominal surgery, and venous blood and peritoneal fluid (PF) samples were obtained. The drug concentrations in plasma and PF were determined and analyzed using population pharmacokinetic modeling. Using the pharmacokinetic model parameters, a Monte Carlo simulation was conducted to estimate the probabilities of attaining the bacteriostatic and bactericidal targets (40% and 70% of the time above the minimum inhibitory concentration (T > MIC), respectively) in PF. The bacteriostatic and bactericidal breakpoints were determined as the highest MIC values at which the bacteriostatic and bactericidal probabilities in PF were > or =80%, which values varied with drug and dosing regimen. Site-specific PK-PD-based breakpoints for CFPM, CTM, CZOP, and FMOX are proposed, and should help us to select appropriate cephems and design their dosing regimens for intraabdominal infections.

β-lactam antibiotic-induced vancomycin resistant MRSA (BIVR) によるマウス感染モデルに対するvancomycinあるいはteicoplaninとβ-lactam薬との併用効果

The concomitant use of low concentration beta-lactam antibiotics antagonizes the activity of vancomycin against some strains of MRSA. These strains, called beta-lactam antibiotic-induced vancomycin resistant MRSA (BIVR), have been increasing for a number of years. We previously reported that the combination of VCM and ceftizoxime displayed this antagonism not only in vitro, but also in vivo, in a systemic infection caused by BIVR in mice. In the present study, we validated the antagonism in combinations of VCM with other beta-lactams, i.e., flomoxef (FMOX), ampicillin (AMPC), azthreonam (AZT) and imipenem/cilastatin (IPM/CS), in systemic infections and pneumoniain in mice. The survival rate of the mice with systemic infections caused by BIVR treated with combinations of FMOX, AMPC, AZT, and IPM/CS with VCM were significantly lower than with VCM monotherapy, and the number of residual viable cells in the kidneys of mice treated with combinations of FMOX and IPM/CS with VCM were significantly higher than with VCM monotherapy The number of residual viable cells in the lungs of mice with pneumonia caused by BIVR treated with the combination of IPM/CS and VCM was significantly higher than with VCM monotherapy. On the other hand, the survival rate with combination therapy consistings IPM/CS plus teicoplanin (T EIC) was significantly higher, and the number of residual viable cells in the kidney was significantly lower, than with TEIC monotherapy alone. In the mice with pneumonia, the number of residual viable cells in the lung after combination therapy with IPM/CS and TEIC was significantly lower than with TEIC monotherapy. Combination therapy with beta-lactams plus VCM showed antagonistic in models of systemic infection and pulmonary infection caused by BIVR, whereas combination therapy consisting of a beta-lactam plus TEIC had a synergistic effect in the same models, even though VCM and TEIC are member of the same glycopeptide antibiotic class.

Influence of various antimicrobial agents on the intestinal flora in an intestinal MRSA-carrying rat model

Using an intestinal methicillin-resistant Staphylococcus aureus (MRSA)-carrying rat model, we compared the influence of piperacillin (PIPC) on the intestinal flora to those of cefazolin (CEZ), cefmetazole (CMZ), and flomoxef (FMOX). The number of MRSA did not increase after PIPC and CEZ administrations compared with the nontreated group. However, it significantly increased in the cases of FMOX and CMZ administration (P < 0.01). In the FMOX- and CMZ-treated groups, the intestinal flora was severely disrupted and the recovery of the number of Escherichia coli and Bacteroides spp. cells was delayed. On the other hand, in the PIPC- and CEZ-treated groups, the rapid recovery of bacteria that composed the intestinal flora was observed. The C(max)/MIC(50) and C(trough)/MIC(50) ratios in E. coli and Bacteroides spp. in the case of FMOX and CMZ were relatively higher than those in the case of the PIPC- and CEZ-treated groups.

Relevance of antimicrobial agent-induced endotoxin release from in vitro cultured Escherichia coli and in vivo experimental infection with Gram-negative bacilli

In vitro exposure of Gram-negative bacilli (GNB) to antimicrobial agents may induce endotoxin (ET) release, that may cause various reactions in vivo resulting in endotoxic shock. We used the antimicrobial agents, flomoxef (FMOX) and gentamicin (GM), to investigate the kinetics of ET released from in-vitro-cultured Escherichia coli and to examine the ET effect on tumor necrosis factor (TNF) production by macrophages. In a rabbit model of E. coli peritonitis, we measured plasma ET, TNF and blood bacterial counts under the administration of FMOX or GM. In our in vitro experiment, ET levels under FMOX were significantly higher than those under GM, and ET induced TNF production in a dose-dependent manner. However, in vivo, plasma ET, TNF, and blood bacterial counts under antimicrobial agents were significantly lower than those of the controls, and those under FMOX treatment did not differ from those under GM treatment. Thus, ET release may not be a critical problem in GNB infections if appropriate antimicrobial agents are administered.

Determination of antibacterial flomoxef in serum by capillary electrophoresis.

A determination method of flomoxef (FMOX) concentration in serum by capillary electrophoresis is developed. Serum samples are extracted with acetonitrile. After pretreatment, they are separated in a fused-silica capillary tube with a 25 mM borate buffer (pH 10.0) as a running buffer that contains 50mM sodium dodecyl sulfate. The FMOX and acetaminophen (internal standard) are detected by UV absorbance at 200 nm. Linearity (0-200 mg/L) is good, and the minimum limit of detection is 1.0 mg/L (S/N = 3). The relative standard deviations of intra- and interassay variability are 1.60-4.78% and 2.10-3.31%, respectively, and the recovery rate is 84-98%. This method can be used for determination of FMOX concentration in serum.

ＦｌｏｍｏｘｅｆとＣｅｆｍｅｔａｚｏｌｅの大腸癌術後感染発症阻止効果における費用対効果分析

The present study was designed to examine the cost-effectiveness of Flomoxef (FMOX) and Cefmetazole (CMZ) in the prophylactic antibiotic therapy after colorectal cancer surgery. Fifty-eight patients (47 in the FMOX group and 11 in the CMZ group), who underwent surgery for colorectal cancer at the First Department of Surgery of our hospital, were investigated. There was no significant difference between the 2 groups regarding the mean treatment period, the prophylactic effect of infection, or in changes in the white blood cell count (WBC), C-reactive protein (CRP), and serum creatinine (Cr) during the treatment period. However, the mean cost of treatment was significantly higher in the FMOX group than in the CMZ group, thus suggesting that the prophylactic effect of CMZ may be more cost-effective. Further evaluations of pharmacotherapy based on cost effectiveness may thus become one of the important duties of hospital pharmacists in the future.