The Japanese journal of antibiotics最新文献

The in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates obtained between 1996 and 2000 were yearly evaluated and compared with those of other cephems, oxacephems, and carbapenems. Thirty-two species 2,697 strains of Gram-negative bacteria were isolated from the clinical materials annually collected from January to December, and consisted of Moraxella subgenus Branhamella catarrhalis (n = 125), Escherichia coli (n = 250), Citrobacter freundii (n = 153), Citrobacter koseri (n = 97), Klebsiella pneumoniae (n = 150), Klebsiella oxytoca (n = 100), Enterobacter aerogenes (n = 50), Enterobacter cloacae (n = 125), Serratia marcescens (n = 153), Proteus mirabillis (n = 103), Proteus vulgaris (n = 77), Morganella morganii (n = 141), Providencia spp. (P. alcalifaciens, P. rettgeri, P. stuartii; n = 154), Pseudomonas aeruginosa (n = 211), Pseudomonas putida (n = 49), Burkholderia cepacia (n = 102), Stenotrophomonas maltophilia (n = 101), Haemophilus influenzae (n = 210), Acinetobactor baumannii (n = 63), Acinetobactor Iwoffii (n = 30), Bacteroides fragilis group (B. fragilis, B. vulgatus, B. distasonis, B. ovatus, B. thetaiotaomicron; n = 129), and Prevotella spp. (P. melaninogenica, P. intermedia, P. bivia, P. oralis, P. denticola; n = 124). 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. lowffii throughout 5 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 65-time difference during 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 the antibacterial activity of CZOP against H. influenzae was suggested.

The in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates obtained between 1996 and 2000 were yearly evaluated and compared with those of other cephems, oxacephems, carbapenems, and penicillins. Fifteen species, 1,062 strains, of Gram-positive bacteria were isolated from the clinical materials annually collected from January to December, and consisted of methicillin-susceptible Staphylococcus aureus (MSSA; n = 127), methicillin-resistant Staphylococcus aureus (MRSA; n = 123), Staphylococcus epidermidis (n = 104), Staphylococcus haemolyticus (n = 58), Streptococcus pyogenes (n = 100), Streptococcus agalactiae (n = 50), Streptococcus pneumoniae (n = 125), Enterococcus faecalis (n = 150), Enterococcus faecium (n = 50), Enterococcus avium (n = 50), and Peptostreptococcus spp. (P. anaerobius, P. asaccharolyticus, P. magnus, P. micros, P. prevotii; n = 125). CZOP possessed stable antibacterial activities against all strains tested throughout 5 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 cefpirome (CPR), cefepime (CFPM), flomoxef (FMOX), sulbactam/cefoperazone (SBT/CPZ), and imipenem (IPM). Increases in the MIC90 against Peptostreptococcus spp. were also observed with ceftazidime (CAZ), CPR, CFPM, FMOX, SBT/CPZ, and IPM. The decreases in the sensitivities were not always considered to depend upon generation of resistant bacteria because the annual MIC range of each antibacterial agent was almost generally wide every year and the annual sensitivity of each strain to the agents extremely varied. 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 5 years of post-marketing.

As a post-marketing surveillance, the in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates were yearly evaluated and compared with those of other cephems, oxacephems, penicillins, monobactams, and carbapenems. Changes in CZOP susceptibility for the bacteria were also evaluated with the bacterial resistance ratio calculated with the breakpoint MIC. Twenty-five species (3,362 strains) of Gram-negative bacteria were isolated from the clinical materials annually collected from 1996 to 2000, and consisted of Moraxella (Branhamella) catarrhalis (n = 136), Haemophilus influenzae (n = 289), Escherichia coli (n = 276), Klebsiella pneumoniae (n = 192), Klebsiella oxytoca (n = 157), Enterobacter cloacae (n = 189), Enterobacter aerogenes (n = 93), Serratia marcescens (n = 172), Serratia liquefaciens (n = 24), Citrobacter freundii (n = 177), Citrobacter koseri (n = 70), Proteus mirabilis (n = 113), Proteus vulgaris (n = 89), Morganella morganii (n = 116), Providencia spp. (n = 41), Pseudomonas aeruginosa (n = 290), Pseudomonas fluorescens (n = 56), Pseudomonas putida (n = 63), Acinetobacter baumannii (n = 146), Acinetobacter lwoffii (n = 34), Burkholderia cepacia (n = 101), Stenotrophomonas maltophilia (n = 169), Bacteroides fragilis group (n = 196), and Prevotella/Porphyromonas (n = 173). An antibacterial activity of CZOP against E. coli, K. pneumoniae, K. oxytoca, and S. marcescens was potent and consistent with or more preferable than the study results obtained until the new drug application approval. MIC90 of CZOP against M.(B.) catarrhalis, C. koseri, and P. aeruginosa was not considerably changed and consistent with the study results obtained until the new drug application approval. MIC90 of CZOP against E. cloacae, E. aerogenes, and P. mirabilis increased year by year. The increase in MIC90 of CZOP against E. aerogenes and P. mirabilis, however, was not considered to be an obvious decline in susceptibility. In contract, the susceptibility of E. cloacae to CZOP was suspected to be decreasing because this species showed 20.6% resistance to CZOP. MIC90 of CZOP against C. freundii was variably changed or not one-sidedly, but was higher than the values obtained until the new drug application approval. Additionally, MIC90 of CZOP against H. influenzae was stable during 5 years except being higher in 1999, and, as a whole, was a little higher than the values obtained until the new drug application approval. An antibacterial activity of CZOP against P. fluorescens, P. putida, B. cepacia, S. maltophilia, B. fragilis group, and Prevotella/Porphyromonas was weak like the other cephems. Changes in MIC90 of CZOP against the other bacteria were 2 tubes or more through 5-year study period, but did not tend towards a unilateral direction as meaning a decline in susceptibility.

As a post-marketing surveillance, the in vitro antibacterial activities of cefozopran (CZOP), an agent of cephems, against various clinical isolates were yearly evaluated and compared with those of other cephems, oxacephems, penicillins, and carbapenems. Changes in the bacterial sensitivity for CZOP were also evaluated with the resistance ratio calculated with breakpoint MIC. Sixteen species (1,913 strains) of Gram-positive bacteria were isolated from the clinical materials annually collected from 1996 to 2000, and consisted of methicillin-susceptible Staphylococcus aureus (MSSA; n = 178), methicillin-resistant S. aureus (MRSA; n = 199), methicillin-susceptible Staphylococcus epidermidis (MSSE; n = 98), methicillin-resistant S. epidermidis (MRSE; n = 164), Staphylococcus haemolyticus (n = 72), Staphylococcus saprophyticus (n = 28), Enterococcus faecalis (n = 206), Enterococcus faecium (n = 91), Enterococcus avium (n = 72), Streptococcus pyogenes (n = 133), Streptococcus agalactiae (n = 138), penicillin-susceptible Streptococcus pneumoniae (PSSP; n = 133), penicillin-intermediate resistant S. pneumoniae (PISP; n = 100), penicillin-resistant S. pneumoniae (PRSP; n = 29), Streptococcus milleri group (n = 135) and Peptostreptococcus spp. (n = 137). CZOP possessed comparable antibacterial activities against MSSA and MSSE to other cephems, and was also effective on MRSE but not on MRSA. An antibacterial activity of CZOP against S. saprophyticus was comparable to or higher than other cephems. CZOP, however, did not indicate an antibacterial activity against S. haemolyticus, just like other cephems. An antibacterial activity of CZOP against E. faecalis was comparable to cefpirome (CPR) and higher than other cephems. No antibacterial activity of CZOP against E. faecium and E. avium was observed, just like other drugs. An antibacterial activity of CZOP against S. pyogenes was as potent as that of cefotiam (CTM), cefepime (CFPM) and CPR, and that against S. agalactiae was also preferable. CZOP and other cephems also had a preferable antibacterial activity against S. milleri group that was most sensitive to benzylpenicillin. An antibacterial activity of CZOP against Peptostreptococcus spp. was preferable but weaker than that of cefazolin, CTM and cefmetazole. The resistance ratio estimated with breakpoint MIC of CZOP was 96.5% in MRSA, 93.1% in PRSP, 60.0% in PISP, 40.3% in S. haemolyticus, 22.3% in E. faecalis, and 15.9% in MRSE. Those resistance ratios were similar to those for CFPM, but E. faecalis showed 90.8% resistance for CFPM. The difference in the resistance ratio of E. faecalis demonstrated that CZOP successfully maintained its antibacterial activity against this species. In conclusion, no remarkable annual change in the antibacterial activities of CZOP against the Gram-positive bacteria was observed. The sensitivities of PISP and PRSP to CZOP, however, was suggested to be decreasing.

We determined the antibacterial activities of 4 carbapenems (imipenem, panipenem, meropenem and biapenem) and 2 forth generation cephems (cefozopran and cefepime) against 850 bacterial strains (18 species) isolated during the period from January 1998 through September 2000. The 4 carbapenems showed excellent antibacterial activities against methicillin-susceptible S. aureus (MSSA), S. pneumoniae, E. faecalis, P. aeruginosa, M. (B). catarrhalis, B. fragilis and Peptostreptococcus spp. as compared with the cephems except the activity of panipenem against P. aeruginosa. Meropenem showed the highest antibacterial activity against 10 species of all Gram-negative strains determined. The antibacterial activities of 2 forth generation cephems against 6 species of Enterobacteriaceae were equal to or higher than those of carbapenems except meropenem. All drugs showed low antibacterial activities against methicillin-resistant S. aureus (MRSA).

Efficacy of panipenem/betamipron (PAPM/BP) against experimental pneumonia caused by penicillin-resistant Streptococcus pneumoniae (PRSP: MIC of benzylpenicillin, > or = 1.56 micrograms/ml) in mice was compared with those of imipenem/cilastatin (IPM/CS), meropenem (MEPM), cefozopran (CZOP), ceftriaxone (CTRX), ampicillin (ABPC), and vancomycin (VCM). The infection was induced by inoculating a PRSP clinical isolate, 9601 (serotype 6) or 10,693 (serotype 19), into ddY male mice intranasally. Drugs were administered subcutaneously at doses of 0.4, 2, and 10 mg/kg, 18, 26, 42, and 50 hours post-infection. Viable cell counts in the lungs were determined 66 hours post-infection. PAPM/BP showed the greatest efficacy against the infections among tested drugs. MICs of PAPM against PRSP 9601 and 10,693 were both 0.125 microgram/ml, which were superior to those of IPM (0.25 and 0.5 microgram/ml, respectively), MEPM (0.5 and 1 microgram/ml, respectively), CZOP (2 and 1 microgram/ml, respectively), CTRX (both 1 microgram/ml), ABPC (both 4 micrograms/ml), and VCM (0.5 and 0.25 microgram/ml, respectively). These results suggest that the potent in vivo activity of PAPM/BP reflects the potent in vitro activity of PAPM. MICs of PAPM, IPM, MEPM, and CZOP against clinical isolates, penicillin-susceptible S. pneumoniae (PSSP: MIC of benzylpenicillin, < or = 0.05 microgram/ml), penicillin-intermediate S. pneumoniae (PISP: MIC of benzylpenicillin, 0.1-0.78 microgram/ml), and PRSP, were tested by an agar dilution method. MIC90s of the drugs against the PSSP, PISP, and PRSP were as follows: PAPM, 0.012, 0.05, and 0.39 microgram/ml; IPM, < or = 0.006, 0.1, and 0.78 microgram/ml; MEPM, 0.05, 0.39, and 1.56 micrograms/ml; and CZOP, 0.2, 0.78, and 6.25 micrograms/ml, respectively. Thus, PAPM showed the most potent activity among tested drugs against clinical isolates of PISP and PRSP.

Effectiveness and safety of cefpirome (CPR) were studied in perinatal infection and prevention of postoperative infections. 1. Enrolled in the study of perinatal infections were the total 62 cases comprising 47 of chorioamnionitis, 10 of puerperal intrauterine infections, 1 of infectious abortion and 4 of others. The effective rate of CPR 2 g/day given in drip infusion was 61/62 (98.4%). In bacteriological studies, the bacterial elimination rate was 57/61 (93.4%). Unchanged and remained were 3 strains of Gram-positive bacteria and 1 strain of Bacteroides spp. 2. Enrolled in the study of prevention of postoperative infections during perinatal period were the total 88 cases comprising 74 who underwent cesarean section and 14 others. The effective rate of CPR 2 g/day given in drip infusion was 87/88 (98.9%). 3. With respect to subjective and objective adverse affects due to the agent, drug eruption was observed in 1/150 (0.7%). No abnormal result of clinical laboratory tests was found. The above results suggested the usefulness of CPR for treatment of perinatal infections and prevention of postoperative infections.

Cefozopran (CZOP) and amikacin (AMK) were used concomitantly to treat infections complicated by hematological diseases. A total of 103 subjects were evaluated, and the all over efficacy rate was 69.9%. Acute leukemia was found in the largest number of patient, 57, followed by 29 cases of malignant lymphoma and 7 cases of myelodysplastic syndrome. By type of infection, patients having unknown origin were the largest in number, being 66, and the efficacy rate was 71.2%. The efficacy rates for sepsis, pneumonia and upper respiratory infection were 42.9% (7 cases), 71.4% (14 cases) and 90% (10 cases) respectively. The efficacy rates by neutrophil counts before administration of CZOP and AMK and at 1 week after administration were both 53.3% in the group of less than 100/microliter, both 60% in the group of less than 500/microliter. The efficacy rate by neutrophil counts at 1 week after administration was 58.6% in the group of less than 100/microliter. The efficacy rate was 75.4% in the group of granulocyte colony stimulating factor (G-CSF) concomitant usage, and 61.9% in the group of non-concomitant usage group. The efficacy rates by serum albumin levels before administration of CZOP and AMK and at 1 week after administration were both 92.9% in the group of over than 4 g/dl, both 50% in the group of less than 3 g/dl. Concomitant treatment with CZOP and AMK exhibited a high level of safety and efficacy rates in infections complicated by hematological diseases.