cefepime and flomoxef

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.

Topics: Abdomen; Anti-Bacterial Agents; Ascitic Fluid; Cefepime; Cefotiam; Cefozopran; Cephalosporins; Enterobacteriaceae; Enterobacteriaceae Infections; Humans; Laparotomy; Microbial Sensitivity Tests; Monte Carlo Method; Postoperative Complications; Surgical Wound Infection

CTX-M-3 has become the most common extended-spectrum beta-lactamase (ESBL) produced by Serratia marcescens in Taiwan. An expanded effort to detect ESBL among 123 nonrepetitive isolates of S. marcescens was made and 15 (12%) ESBL-producers were identified, all revealing CTX-M-3. Without routinely detecting the ESBL for S. marcescens in clinical laboratories, 80% of the ESBL-producers were reported to be susceptible to cefepime. The clinical spectrum of ESBL-producing S. marcescens-related infections included febrile urinary tract infection (n = 3); afebrile pyuria (n = 2); pneumonia (n = 3); spontaneous bacterial peritonitis (n = 3); secondary bacteremia (n = 2) and one each with primary bacteremia and colonization of the central catheter tip. Overall, the 30-day mortality rate was 33.3% (5/15) and the outcome depended on the severity of the underlying disorder and infection per se. In conclusion, although our case numbers were limited, due to the substantial incidence and associated mortality of ESBL-producing S. marcescens and its potential treatment failure by an apparently susceptible cephalosporin, we recommend that the detection and report of ESBL production for S. marcescens in clinical laboratories be made mandatory.

Topics: Amikacin; beta-Lactamase Inhibitors; beta-Lactamases; Carbapenems; Cefepime; Cephalosporins; Electrophoresis, Gel, Pulsed-Field; Humans; Imipenem; Microbial Sensitivity Tests; Molecular Epidemiology; Molecular Sequence Data; Polymerase Chain Reaction; Serratia Infections; Serratia marcescens; Taiwan

The in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates obtained between 1996 and 2001 were yearly evaluated and compared with those of other cephems, oxacephems, carbapenems, and penicillins. A total of 1,274 strains in 15 species of Gram-positive bacteria were isolated from the clinical materials annually collected from January to December, and consisted of methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis, Staphylococcus haemolyticus, Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, Enterococcus faecalis, Enterococcus faecium, Enterococcus avium, and Peptostreptococcus spp. CZOP possessed stable antibacterial activities against all strains tested throughout 6 years. The MIC90 of CZOP against MRSA and S. haemolyticus tended to decrease while against S. pneumoniae and Peptostreptococcus spp., tended to increase year by year. However, the MIC90 just changed a little and were consistent with the results from the studies performed until the new drug application approval. Increases in the MIC90 against S. pneumoniae were also observed with ceftazidime (CPR), cefepime (CFPM), flomoxef (FMOX), sulbactam/cefoperazone (SBT/CPZ), and imipenem (IPM). Increases in the MIC90 against Peptostreptococcus spp. were also observed with FMOX, SBT/CPZ, and IPM. In conclusion, the annual antibacterial activities of CZOP against the Gram-positive bacteria did not considerably change. It, therefore, was suggested that CZOP had maintained high antibacterial activity during 6 years of post marketing.

Topics: Cefepime; Cefozopran; Cephalosporins; Gram-Positive Bacteria; Humans; Methicillin Resistance; Microbial Sensitivity Tests; Staphylococcus; Staphylococcus aureus

The in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates obtained between 1996 and 2001 were yearly evaluated and compared with those of other cephems, oxacephems and carbapenems. A total of 3,245 strains in 32 species of Gram-negative bacteria were isolated from the clinical materials annually collected from January to December, and consisted of Moraxella subgenus Branhamella catarrhalis, Escherichia coli, Citrobacter freundii, Citrobacter koseri, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter cloacae, Serratia marcescens, Proteus mirabillis, Proteus vulgaris, Morganella morganii, Providencia spp. (P. alcalifaciens, P. rettgeri, P. stuartii), Pseudomonas aeruginosa, Pseudomonas putida, Burkholderia cepacia, Stenotrophomonas maltophilia, Haemophilus influenzae, Acinetobactor baumannii, Acinetobactor lwoffii, Bacteroides fragilis group (B. fragilis, B. vulgatus, B. distasonis, B. ovatus, B. thetaiotaomicron), and Prevotella spp. (P. melaninogenica, P. intermedia, P. bivia, P. oralis, P. denticola). CZOP possessed stable antibacterial activities against M. (B.) catarrhalis, E. coli, C. freundii, C. koseri, K. pneumoniae, K. oxytoca, E. aerogenes, E. cloacae, S. marcescens, P. mirabilis, P. vulgaris, M. morganii, Providencia spp., P. aeruginosa, and A. lwoffii throughout 6 years. The MIC90 of CZOP against those strains were consistent with those obtained from the studies performed until the new drug application approval. On the other hand, the MIC90 of CZOP against H. influenzae yearly obviously increased with approximately 64-time difference during the study period. The MIC90 of cefpirome, cefepime, and flomoxef against H. influenzae also yearly tended to rise. The present results demonstrated that CZOP had maintained the antibacterial activity against almost Gram-negative strains tested. However, the decrease in antibacterial activities of CZOP against B. cepacia, and H. influenzae was suggested.

Topics: Cefepime; Cefoperazone; Cefozopran; Cefpirome; Cephalosporins; Drug Resistance, Bacterial; Escherichia coli; Gram-Negative Bacteria; Humans; Moraxella

In this study, we evaluated the current effectiveness of 11 beta-lactam antibiotics for treatment of orofacial odontogenic infections by determining the antimicrobial susceptibility of the major pathogens. The antimicrobial susceptibilities of viridans streptococci (n = 47), Peptostreptococcus (n = 67), Porphyromonas (n = 18), Fusobacterium (n = 57), black-pigmented Prevotella (n = 59) and non-pigmented Prevotella (n = 47) isolated from pus specimens of 93 orofacial odontogenic infections to penicillin G, cefmetazole, flomoxef, cefoperazone, cefoperazone/sulbactam, ceftazidime, cefpirome, cefepime, cefoselis, imipenem and faropenem were determined using the agar dilution method. Penicillin G, most cephalosporins, imipenem and faropenem worked well against viridans streptococci, Peptostreptococcus, Porphyromonas and Fusobacterium. Penicillin G and most cephalosporins, including fourth-generation agents, were not effective against beta-lactamase-positive Prevotella, though they were effective against beta-lactamase-negative strains. Cefmetazole, cefoperazone/sulbactam, imipenem and faropenem expressed powerful antimicrobial activity against beta-lactamase-positive Prevotella. In conclusion, penicillins have the potential to be first-line agents in the treatment of orofacial odontogenic infections. Most of the other beta-lactam antibiotics, including fourth-generation cephalosporins, were not found to have greater effectiveness than penicillins. In contrast, cefmetazole, cefoperazone/sulbactam, imipenem and faropenem were found to have greater effectiveness than penicillins.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacteroidaceae Infections; beta-Lactams; Cefepime; Cefmetazole; Cefoperazone; Cefpirome; Ceftazidime; Ceftizoxime; Cephalosporins; Drug Resistance, Bacterial; Drug Therapy, Combination; Fusobacterium; Fusobacterium Infections; Gram-Positive Bacterial Infections; Humans; Imipenem; Lactams; Microbial Sensitivity Tests; Mouth Diseases; Penicillin G; Penicillins; Peptostreptococcus; Porphyromonas gingivalis; Prevotella; Streptococcal Infections; Streptococcus; Sulbactam

In vitro combination effect of teicoplanin and beta-lactams was investigated against 109 MRSA strains isolated from a variety of clinical specimens at the Social Health Insurance Medical Center during the period from January 1994 through February 2000. TEIC + panipenem (PAPM) was revealed by microbroth dilution method-based checkerboard method, to exhibit synergistic effect of min. FIC index < or = 0.5 against all the 109 strains. The combination of TEIC and flomoxef (FMOX) was shown to have synergistic effect on 108 strains (99.1%). The combination of TEIC and cefepime (CFPM) was shown to have synergistic effect on 96 strains (88.1%). The combination of TEIC and cefmetazole (CMZ) was shown to have synergistic effect on all the 109 strains (100%). The mean value of min. FIC indices obtained from each of the combinations was 0.1259 as to TEIC + PAPM, 0.2019 as to TEIC + FMOX, 0.3257 as to TEIC + CFPM and 0.1995 as to TEIC + CMZ, in other words, the combination of TEIC + PAPM showed the lowest value of all the combinations. While MIC80 was 2.0 micrograms/ml when TEIC was used alone, it was < or = 0.06 microgram/ml when used together with PAPM, and 0.13 microgram/ml when used together with FMOX, respectively. While MIC80 was 3.2 micrograms/ml when PAPM was used alone, it was 0.5 microgram/ml when used together with TEIC. Meanwhile, the value for FMOX was changed from > or = 128 micrograms/ml to 4.0 micrograms/ml. When TEIC was used in combination with CFPM, MIC80 was found to be 0.5 microgram/ml. Similar to the case of the concurrent use with FMOX, the value obtained by combination with CMZ was 0.13 microgram/ml. While MIC80 was 128 micrograms/ml when CFPM was used alone, it was 8.0 micrograms/ml when used together with TEIC, whereas the value for CMZ was decreased from 64 micrograms/ml to 2.0 micrograms/ml. In conclusion, TEIC's antibacterial activity was shown to be accentuated by any of the combinations.

Topics: Anti-Bacterial Agents; Cefepime; Cefmetazole; Cephalosporins; Cephamycins; Drug Synergism; Methicillin Resistance; Microbial Sensitivity Tests; Staphylococcus aureus; Teicoplanin; Thienamycins