Combined effects of arbekacin with other antibiotics against methicillin-resistant Staphylococcus aureus. II. The combined effect of arbekacin with imipenem or cefminox]

Combined antibacterial effects of imipenem (IPM)+arbekacin (ABK) and cefminox (CMNX)+ABK against methicillin-resistant Staphylococcus aureus (MRSA) were examined and the obtained results are summarized below. 1. Either combination, IPM+ABK or CMNX+ABK, showed a strong antibacterial effect against MRSA when blood concentration of ABK were sustained at MIC as could be expected in clinical situations. While at sub MICs of ABK the antibacterial effect of these combination was slightly less than those of the previously reported combinations of ABK and other antibiotics. 2. Antibacterial effects of the combinations against MRSA were strongly dependent on the concentration of ABK and less dependent on the concentration of IPM or CMNX. As were observed in the previously tested combinations of ABK with other antibiotics, the antibacterial effect of the combination appeared to be highly dependent on the antibacterial activity and the concentration of ABK. 3. As IPM has potent antibacterial activities against Gram-negative bacteria (GNB) including Pseudomonas aeruginosa while CMNX has potent antibacterial activities against GNB except P. aeruginosa, it is likely that the combinations of IPM+ABK or CMNX+ABK are useful for treatment of infections with MRSA together with GNB.     

Susceptibility of clinically isolated strains to aztreonam

In vitro antibacterial activities of aztreonam (AZT) and cephems against clinically isolated 334 strains were investigated. The results obtained in the study are summarized as follows: 1. AZT showed excellent antibacterial activities against clinically isolated 334 strains. 2. AZT showed potent activities against Escherichia coli, Klebsiella pneumoniae, Proteus spp., Enterobacter aerogenes and Citrobacter freundii. 3. Antibacterial activities of AZT were superior against Enterobacter cloacae, Serratia marcescens and Pseudomonas aeruginosa to those of cephems.     

Susceptibilities of clinical bacterial isolates to antimicrobial agents. A study mainly focused on imipenem. Reported by the Research Group for Testing Imipenem Susceptibility on Clinical Isolates

This study was conducted to investigate susceptibilities of clinical bacterial isolates to imipenem (IPM) and other antibacterial agents at 64 hospital laboratories throughout Japan from September to December of 1988. In this study, identification and susceptibility testing were carried out at each laboratory and the tests were performed according to the disk dilution method recommended by NCCLS in which susceptibilities are classified into "S", "MS", "I" and "R". IPM showed markedly high in vitro activities against Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae, Enterococcus faecalis, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter cloacae, Serratia marcescens, Salmonella spp., Citrobacter freundii, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia rettgeri, Providencia stuartii, Acinetobacter calcoaceticus, Moraxella (Branhamella) catarrhalis, Alcaligenes spp., Peptococcus spp./Peptostreptococcus spp., Bacteroides fragilis and Bacteroides spp. IPM also had strong activities against Achromobacter xylosoxidans and Pseudomonas aeruginosa, but less active against Flavobacterium spp., E. faecium, coagulase-negative staphylococci (CNS), Staphylococcus aureus and Pseudomonas cepacia. In a study in which activities of IPM against bacteria isolated from different clinical sources were compared, differences in susceptibilities were observed among S. aureus, CNS, A. calcoaceticus and P. aeruginosa, but such differences were not apparent among S. pneumoniae, E. faecalis, H. influenzae, E. coli, K. pneumoniae, E. cloacae, C. freundii, S. marcescens or P. mirabilis.     

In vitro and in vivo antibacterial activities of pazufloxacin mesilate,a new injectable quinolone

We investigated the in vitro and in vivo antibacterial activities of pazufloxacin mesilate (PZFX mesilate), a new injectable quinolone, and obtained the following results. 1) The MIC50 and MIC90 values of PZFX against clinically isolated Gram-positive and -negative bacteria, ranged from 0.0125 to 12.5 micrograms/ml and 0.025 to 100 micrograms/ml, respectively. PZFX showed broad spectrum activity. The antibacterial activities of PZFX against quinolone-susceptible, methicillin-resistant Staphylococcus aureus, beta-lactamase-negative, ampicillin-resistant Haemophilus influenzae, extended spectrum beta-lactamase possessing Klebsiella pneumoniae and imipenem/cilastatine (IPM/CS)-resistant Pseudomonas aeruginosa were superior to those of ceftazidime (CAZ), ceftriaxone, IPM/CS, meropenem and panipenem/betamipron. 2) PZFX showed superior bactericidal activity against S. aureus, Escherichia coli, Proteus mirabilis, Serratia marcescens and P. aeruginosa to those of CAZ and IPM/CS after treatment for 15 minutes at the drug concentration equivalent to that in human serum at clinical dose to be continued for 15 minutes. 3) CAZ and IPM/CS had no bactericidal activity at the 16 times of MIC against P. aeruginosa in human polymorphonuclear leucocytes, while PZFX exhibited potent bactericidal activity in a dose-dependent manner against such bacteria. 4) PZFX inhibited both DNA gyrase and topoisomerase IV from S. aureus at nearly the same level. PZFX showed poor inhibitory activity against topoisomerase II from human placenta and showed high selectivity to bacterial topoisomerase. 5) PZFX mesilate showed superior therapeutic activity to that of CAZ with following infection model caused by S. aureus and P. aeruginosa or each; systemic infection with cyclophosphamide-treated mice, systemic infection in mice with high challenge doses, CMC pouch infection in rat, and calculus infection in rat bladder. 6) Intravenous administration of PZFX with high plasma concentration just after administration, showed more excellent therapeutic effect against the rat intraperitoneal infection, than p.o. and s.c. administration.     

Antibacterial activities of new cephems against clinically isolated organisms (author's transl)

The antibacterial activities of cefotaxime (CTX), cefoperazone (CPZ), ceftizoxime (CZX), cefmenoxime (CMX), latamoxef (LMOX), cefotiam (CTM), cefazolin (CEZ), gentamicin (GM) and cefsulodin (CFS) were investigated. All causative organisms were isolated from patients with urinary tract infections treated in Tokai University Hospital. The results were as follows. 1) The MICs of CMX, CTX, and CZX against most of clinically isolated strains of E. coli, K. pneumoniae, Indole (-) Proteus sp. were 0.1 microgram/ml and lower. And then CTM, LMOX and CPZ showed similar antibacterial activities. 2) LMOX and GM showed potent antibacterial activities against C. freundii which was considered to be causative organisms of infections in rare cases. 3) Against S. marcescens, CMX, CTX, CZX, and LMOX showed very potent antibacterial activities. 4) Against P. aeruginosa, CFS, GM and CPZ showed moderate antibacterial activities. 5) Against Enterobacter sp., GM and CMX showed potent antibacterial activities.     

A study on in vitro antibacterial activity and clinical usefulness in respiratory tract infections of panipenem/betamipron, a newly synthesized carbapenem antibiotic]

Panipenem/betamipron (PAPM/BP) is a combination drug of PAPM, a new parenteral carbapenem antibiotic and BP, an amino acid derivative at a weight ratio of 1:1. Its in vitro antibacterial activities against clinically isolated respiratory pathogenic bacteria were determined. It was superior to imipenem (IPM) in the in vitro antibacterial activities against Haemophilus influenzae, Haemophilus parainfluenzae, Branhamella catarrhalis, Staphylococcus aureus including MRSA, Klebsiella pneumoniae, Serratia marcescens and Escherichia coli. PAPM had antibacterial activities almost equal to those of IPM against Streptococcus pneumoniae and Enterococcus spp. Against Pseudomonas aeruginosa, however, its antibacterial activity was about 1/4 that of IPM. The clinical usefulness of PAPM/BP was studied by dissolving it in a solution containing lactate and administering the solution by intravenous drip infusion to 12 cases of respiratory tract infections. Out of 11 cases with respiratory tract infections excluding cytomegalovirus pneumonia, the efficacy rate was 90.9%, with 4 cases of excellent and 6 cases of good responses. In terms of its bacteriological efficacies, eradication of pathogenic bacteria including super-infection were observed in 2 out of 4 strains, but 2 strains of P. aeruginosa remained unchanged. Six strains appeared as superinfected bacteria during and after administration of this preparation substituting original pathogens. Side-effects were not observed in the 12 cases, and in laboratory tests, slight transient increases of S-GOT and S-GPT were found in 1 case. In conclusion, PAPM/BP is a very useful parenteral antibiotic against respiratory tract infections and can be one of the drugs of the first choice.     

Antibacterial activities of sisomicin against fresh clinical isolates]

To investigate antibacterial activities of sisomicin (SISO), MICs of SISO as well as other aminoglycosides (AGs) were determined against many clinical isolates which were obtained in 1991. Results are summarized below: 1. No SISO-resistant strains were observed among isolates of Escherichia coli, Citrobacter diversus, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Proteus mirabilis and Morganella morganii. 2. In comparison with the results of our previous study against isolates obtained in 1986, the rate of methicillin-resistant Staphylococcus aureus (MRSA) was higher, and SISO-resistant strains were observed at a high rate among the MRSA. Also, SISO-resistant strains of Serratia marcescens increased. However, the rate of SISO-resistant strains of Pseudomonas aeruginosa decreased, and among Citrobacter freundii, Enterobacter cloacae and Proteus vulgaris, SISO-resistant strains did not increase over the years. 3. MICs of SISO against Providencia rettgeri and Providencia stuartii were high, suggesting that antibacterial activities of SISO was weak against genus Providencia. 4. For comparison, according to MICs of ofloxacin and imipenem, new quinolone-resistant strains were observed at a high rate among various organisms, and carbapenem-resistant strains were observed at a high rate among S. marcescens and P. aeruginosa. 5. SISO is still one of the useful AGs in the 1990's since it maintains its strong antibacterial activities against most clinical isolates obtained in recent years and its potential as a combination drug with beta-lactams is being reported.     

Susceptibilities of clinical bacterial isolates to antimicrobial agents, 1989. A study mainly focused on imipenem. The Research Group for Testing Imipenem Susceptibilities of Clinical Isolates]

We investigated susceptibilities of clinical bacterial isolates to imipenem (IPM) and other antimicrobial agents at hospital laboratories throughout Japan from September to December of 1989. The susceptibility testing was carried out according to the 1-dilution or 3-dilution disc technique in which susceptibilities are classified into 4 grades: (+++), (++), (+) and (-). IPM showed markedly high in vitro activities against Streptococcus pneumoniae, Neisseria gonorrhoeae, Moraxella catarrhalis, Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Citrobacter freundii, Acinetobacter calcoaceticus, Bacteroides fragilis and had rather strong activities against Enterococcus faecalis, Haemophilus influenzae, Serratia marcescens, Proteus mirabilis, Morganella morganii, Pseudomonas aeruginosa and Achromobacter xylosoxidans, but was less active to Staphylococcus aureus, coagulase-negative staphylococci and Xanthomonas maltophilia. IPM has been found to have activities superior to those of other antibiotics tested against E. faecalis, E. cloacae, C. freundii, S. marcescens, P. aeruginosa and B. fragilis. No antibiotics tested showed good activities against MRSA except minocycline.     

Yearly changes in antibacterial activities of cefozopran against various clinical isolates between 1996 and 2001--I. Gram-positive bacteria

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.     

Evaluation of the activity and effects of combinations of various antibacterial agents against methicillin-resistant Staphylococcus aureus in vitro

MICs of various antibacterial agents against methicillin-resistant Staphylococcus aureus (MRSA) were measured. Furthermore, we evaluated the effects of combinations of antibacterial agents against MRSA in vitro. In 24 cases out of 37, in which MRSA was isolated from inpatients, other microorganisms, such as Candida spp., Entrococcus spp., and Pseudomonas aeruginosa, were simultaneously isolated. From the results of minimum inhibitory concentrations (MICs), obtained from micro broth-dilution method, of various antibacterial agents against MRSA, range of MICs of arbekacin (ABK), vancomycin (VCM) and teicoplanin (TEIC) were < or = 0.25-4.0, 0.5-1.0 and 0.25-4.0 micrograms/ml respectively, and no strains of MRSA showed resistance to ABK, VCM and TEIC, so that we concluded that these three antibacterial agents were effective for MRSA infection. On the in vitro study of combination-effect of antibacterial agents, significant synergistic effects were achieved in the combination of VCM and flomoxef (FMOX) (Synergism rate was 97.3%) or VCM and imipenem (IPM) (Synergism rate was 97.2%). From the results that the fractional inhibitory concentration index in the combination of VCM with IPM was smaller than that with FMOX and that P. aeruginosa or Enterococcus spp. were simultaneously isolated in high frequency in the MRSA-isolated cases, we thought that the combination of VCM with IPM is more useful, because IPM is effective against P. aeruginosa but FMOX is not.     

In vitro activity of biapenem (BIPM) against clinically isolated respiratory pathogens in 1996-1998

The in vitro antibacterial activity of biapenem (BIPM), a new carbapenem antibiotic, was compared with those of imipenem (IPM), panipenem (PAPM), meropenem (MEPM), ceftazidime (CAZ) and piperacillin (PIPC) against 280 isolates of 9 respiratory pathogens. The MIC90s of biapenem (BIPM) for methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, Moraxella catarrhalis, Pseudomonas aeruginosa, and Haemophilus influenzae were 0.12, 32, 0.25, 0.06, 4 and 8 micrograms/ml, respectively. In comparison with other antibiotics, the activity of biapenem (BIPM) for P. aeruginosa was as potent as meropenem (MEPM), but for H. influenzae it was slightly less than those of other antibiotics, and for other respiratory pathogens it was as potent as those of other antibiotics. The MIC90s of biapenem (BIPM) for Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae and Serratia marcescens were 0.06, 1, 1, 0.5 microgram/ml, respectively, and which were equal to or somewhat lower than those of other antibiotics. Biapenem (BIPM) showed strong activity against Gram-positive and Gram-negative pathogens, especially P. aeruginosa in general. Based on these results, biapenem (BIPM) is seemed to be highly useful antibiotic for the treatment of respiratory infections with several organism.     

In-vitro activity of panipenem against clinical isolates in 2006

The antimicrobial activity of various antibiotics against clinical bacterial isolates recovered from patients with infectious diseases at the medical facilities in the Kanto region between March and September 2006 was evaluated. A total of 1030 clinical isolates were available for susceptibility tests: 420 aerobic Gram-positive organisms, 520 aerobic Gram-negative organisms, 30 anaerobic Gram-positive organisms and 60 anaerobic Gram-negative pathogens. Antimicrobial susceptibility data for Streptococcus pneumoniae and Haemophilus influenzae isolates from pediatric and adult patients were analyzed separately. Panipenem (PAPM), imipenem (IPM), meropenem (MEPM), biapenem (BIPM), doripenem (DRPM), cefozopran (CZOP), cefepime (CFPM), and sulbactam/cefoperazone (SBT/CPZ) were used as test antibiotics. PAPM, IPM and DRPM exhibited excellent in vitro antibacterial activities against methicillin-susceptible Staphylococcus, with all isolates exhibiting a MIC of < or =0.06 microg/mL. Against Streptococcus including penicillin-resistant S. pneumoniae, PAPM demonstrated the strongest antibacterial activity among the carbapenems with a MIC range of < or =0.06 to 0.12 microg/mL. Against Enterobacteriaceae, MEPM showed the strongest antibacterial activity, and PAPM had comparable activity to IPM. Against the extended-spectrum beta-lactamase producing Escherichia coli, Klebsiella species and Proteus species, the MICs for the cephems were high, however, those for the carbepenems were low. Against H. influenzae, PAPM had comparable activity to IPM. With respect to anaerobes, each of the carbapenems tested demonstrated almost the same strong antibacterial activity. In conclusion, 13 years has passed since PAPM was launched in 1993, PAPM still maintains potent antibacterial activity and is considered an effective antimicrobial agent for various types of infectious diseases.     

Changes in the antibacterial activity of chemotherapeutic agents (especially carbapenems) for 10 species of clinical isolates between 1994 and 1996. Surveillance group of the sensitivities of clinical isolates to antibacterial agents

During October and December of each year of from 1994 to 1996, 3,849 strains of 10 species of bacteria were isolated from clinical materials in 21 institutions nationwide. The minimum inhibitory concentrations (MICs) for these bacteria of four carbapenems (imipenem [IPM], panipenem [PAPM], meropenem [MEPM], and biapenem [BIPM]) and other representative antibacterial agents were measured to investigate annual changes in antibacterial activity. Carbapenems showed potent activity against methicillin-sensitive S. aureus (MSSA), S. pneumoniae, E. faecalis, H. influenzae, E. coli, K. pneumoniae, E. cloacae, S. marcescens, and the B. fragilis group, with the activity being stable. However, these drugs showed weak activity against methicillin-resistant S. aureus (MRSA) and P. aeruginosa. The antibacterial activity (MIC90) against the tested organisms generally remained stable. Particularly, there was annual improvement of the MIC90 values of IPM and BIPM for S. pneumoniae, as well as the values of IPM and PAPM for H. influenzae, and those of IPM, PAPM, and BIPM for S. marcescens. On the other hand, the activity of carbapenems (including IPM) against MRSA was not necessarily strong, but there was annual improvement of MIC90 values.     

Nationwide surveillance of parenteral antibiotics containing meropenem activities against clinically isolated strains in 2006

The antibacterial activity of meropenem (MEPM) and other parenteral antibiotics against clinical isolates of 876 strains of Gram-positive bacteria, 1764 strains of Gram-negative bacteria, and 198 strains of anaerobic bacteria obtained from 30 medical institutions during 2006 was measured. The results were as follows; 1. MEPM was more active than the other carbapenem antibiotics tested against Gram-negative bacteria, especially against enterobacteriaceae and Haemophilus influenzae. MEPM was also active against most of the species tested in Gram-positive and anaerobic bacteria, except for multi-drug resistant strains including methicillin-resistant Staphylococcus aureus. 2. As for Pseudomonas aeruginosa, all of the MEPM-resistant strains were resistant to imipenem (IPM). MEPM showed low cross-resistant rate both againt IPM-resistant P. aeruginosa (41.8%) and ciprofloxacin-resistant P. aeruginosa (33.3%). 3. The proportion of extended-spectrum beta-lactamase (ESBL) strains was 4.3% (6 strains) in Escherichia coli, 1.1% (1 strain) in Citrobacter freundii, 21.7% (5 strains) in Citrobacter koseri, 3.1% (4 strains) in Klebsiella pneumoniae, 3.3% (3 strains) in Enterobacter cloacae, 0.8% (1 strain) in Serratia marcescens, and 4.9% (2 strains) in Providencia spp. The proportion of metallo-beta-lactamase strains was 3.1% (10 strains) in P. aeruginosa. 4. Of all species tested, there were no species, which MIC90 of MEPM was more than 4-fold higher than those in our previous study. Therefore, there is almost no significant decrease in susceptibility of clinical isolates to meropenem. In conclusion, the results from this surveillance study suggest that MEPM retains its potent and broad antibacterial activity and therefore is a clinically useful carbapenem at present, 11 years after available for commercial use.     

Susceptibility of clinical isolates to aztreonam

In vitro antibacterial activities of 9 antibiotics including aztreonam (AZT) against clinically isolated Gram-negative bacteria were determined using MIC-2000 plus system. Bacteria were isolated from clinical materials in Saga Medical School during a period from May 1987 to March 1988. Summarized results were as follows: 1. AZT showed excellent antibacterial activities against Escherichia coli, Klebsiella pneumoniae, Proteus sp. and Haemophilus influenzae, and MIC80 values of AZT against these organisms were lower than 0.20 microgram/ml. 2. Antibacterial activities of AZT were superior to cephem antibiotics compared against Enterobacter aerogenes, Enterobacter cloacae, Citrobacter freundii and Serratia marcescens. 3. The MIC50 and MIC80 of AZT against Pseudomonas aeruginosa were 12.5 micrograms/ml and 25 micrograms/ml, respectively. 4. AZT did not show any antibacterial activity against Acinetobacter sp. and Xanthomonas maltophilia.     

Post-marketing surveillance of antibacterial activities of cefozopran against various clinical isolates--II. Gram-negative bacteria

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, carbapenems, monobactams, and penicillins. Changes in CZOP susceptibility among bacteria were also evaluated with the bacterial resistance ratio calculated from the breakpoint MIC. Twenty-five species (4,154 strains) of Gram-negative bacteria were isolated from the clinical materials annually collected from 1996 to 2001, and consisted of Moraxella (Branhamella) catarrhalis, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens, Serratia liquefaciens, Citrobacter freundii, Citrobacter koseri, Proteus mirabilis, Proteus vulgaris, Morganella morganii, Providencia spp., Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas putida, Acinetobacter baumannii, Acinetobacter Iwoffii, Burkholderia cepacia, Stenotrophomonas maltophilia, Bacteroides fragilis group, and Prevotella/Porphyromonas. CZOP preserved its antibacterial activity against M. (B.) catarrhalis (MIC90: 4 micrograms/mL) and showed comparable activity to carbapenems against H. influenzae (MIC90: 1 microgram/mL). The antibacterial activity of CZOP against E. coli was preferable (MIC90: 0.125 microgram/mL) and comparable to those of cefpirome (CPR), cefepime (CFPM), and imipenem (IPM). The MIC90 of CZOP against K. pneumoniae and K. oxytoca was 1 and 0.25 microgram/mL, respectively. The MIC90 of CZOP against E. cloacae increased during 6 years (32 to 128 micrograms/mL). The antibacterial activity of CZOP against E. aerogenes was preferable (MIC90: 1 microgram/mL). The antibacterial activities of CZOP against S. marcescens and S. liquefaciens were relatively potent (MIC90: 0.5 and 0.25 microgram/mL) and comparable to those of CPR, CFPM, and carumonam. CZOP preserved comparable antibacterial activity to CPR against C. freundii and C. koseri (MIC90: 8 and 0.125 micrograms/mL). The MIC90 of CZOP against P. mirabilis, P. vulgaris, and M. morganii was 0.25, 16, and 2 micrograms/mL, respectively. The antibacterial activity of CZOP against Providencia spp. was moderate (MIC90: 64 micrograms/mL). The antibacterial activity of CZOP against P. aeruginosa was the most potent (MIC90: 16 micrograms/mL) among the test agents and comparable to those CFPM, IPM, and MEPM. CZOP had low activity against P. fluorescens and P. putida (MIC90: 128 micrograms/mL). The antibacterial activity of CZOP against A. baumannii was comparable to those of ceftazidime (CAZ), CPR and CFPM (MIC90: 32 micrograms/mL) and against A. lwoffii was moderate (MIC90: 64 micrograms/mL). Most of the test agents including CZOP had low antibacterial activity against B. cepacia, S. maltophilia, and B. fragilis group. The MIC90 of CZOP against Prevotella/Porphyromonas was 64 micrograms/mL. Bacterial cross-resistance ratio between CZOP and other agents was low in most of the species, ranging from 0.0 to 15.1%. In non-glucose fermentative bacteria, however, the bacterial cross-resistance ratio between CZOP and CFPM, CAZ, CPR, or IPM was high, being 36.8%, 28.0%, 38.7%, or 31.1%, respectively. In conclusion, the 6-year duration study suggested that the antibacterial activity of CZOP against E. cloacae possible decreased, but against other Gram-negative bacteria was consistent with the study results obtained until the new drug application approval.     

Antimicrobial activity of meropenem against main bacterial species isolated from patient blood in 2010

We investigated antimicrobial activities of meropenem and other antibiotics against 164 isolates (41 Escherichia coli, 16 Klebsiella pneumoniae, 7 Enterobacter cloacae, 21 Pseudomonas aeruginosa, 14 methicillin-susceptible Staphylococcus aureus (MSSA), 18 methicillin-resistant Staphylococcus aureus (MRSA), 47 Staphylococcus epidermidis) from blood of the patients admitted to Keio University Hospital between January and October in 2010. Meropenem showed the potent antibacterial activity against Gram-negative bacteria especially and it maintained good broad spectrum antimicrobial activity including resistant strains through 13 years since when we started the investigation. These results indicated the validity of choosing meropenem as a first line antimicrobial agent for serious infectious diseases.     

An in vitro study on combination effect of isepamicin and beta-lactam antibiotics

A study was done on the combined actions of an aminoglycoside, isepamicin (ISP), and 3 beta-lactam antibiotics (cefoperazone (CPZ), latamoxef (LMOX) and imipenem/cilastatin sodium (IPM/CS] against clinical isolates of Pseudomonas aeruginosa, Serratia marcescens and Klebsiella pneumoniae. Minimal inhibitory concentrations of individual antibiotics were compared first. ISP and IPM/CS had strong antibacterial activities against all 3 bacterial species while the antibacterial activities of CPZ against P. aeruginosa and S. marcescens, and that of LMOX against P. aeruginosa were much weaker than those of IPM/CS or ISP. Fractional inhibitory concentration indices determined by the checker-board dilution method were compared next. ISP, when used in combination with beta-lactam antibiotics (CPZ, LMOX, or IPM/CS), showed synergistic or additive effect on most strains of the all 3 species, the combination of ISP and CPZ being most effective. Although less effective, synergistic or additive effects were also observed with the combinations of 2 beta-lactam antibiotics (CPZ and IPM/CS, LMOX and IPM/CS). Time course experiments demonstrated that ISP combined with CPZ had bactericidal activities against all 3 bacterial species at concentrations at which the respective drug alone showed only bacteriostatic activity.     

Yearly changes in antibacterial activities of cefozopran against various clinical isolates between 1996 and 2000--I. Gram-positive bacteria

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.     

头孢地尼与其他6种β-内酰胺类的体外抗菌活性研究

目的　比较头孢地尼与头孢克肟、头孢克洛、头孢呋辛、头孢拉定、头孢氨苄、阿莫西林对临床常见致病菌的体外抗菌活性。方法　采用琼脂平板稀释法测定最低抑菌浓度 (MIC)。结果　头孢地尼对金黄色葡萄球菌、表皮葡萄球菌的敏感率分别为 73 3%、90 % ,抗菌活性显著强于头孢克肟 ;对肺炎克雷伯氏菌的活性与头孢克肟相似 ,强于受试第一代、二代头孢菌素 ;对大肠埃希氏菌活性强于其他 6种抗生素 ;对变形菌活性与头孢克肟相似。阴沟肠杆菌、柠檬酸杆菌属对受试药物耐药性均较高 ,其中头孢地尼和头孢克肟的敏感率 40 %左右 ,较其他 5种抗生素为强。结论　头孢地尼对大部分革兰氏阳性及革兰氏阴性菌具有较强的抗菌活性。