Therapeutic effects of cefpirome, a new cephalosporin, on various models of infections in mice and rats

Cefpirome (HR 810) is a new cephalosporin with a 2,3-cyclopentenopyridine group in the 3-position side chain. It was compared with other cephem antibiotics in protective and therapeutic effects on various experimental infections, systemic and local, in mice and rats. HR 810 had more potent protective effect than ceftazidime (CAZ), cefoperazone (CPZ), and cefotaxime (CTX) on systemic infections induced by Escherichia coli Ec-31, Staphylococcus aureus SMITH, and Serratia marcescens Sm-6 in mice. Against systemic infection with Pseudomonas aeruginosa HR 810 was as effective as CAZ. Mice with leukopenia induced by cyclophosphamide were systemically infected with methicillin-resistant S. aureus (MRSA), methicillin-susceptible S. aureus (MSSA), Enterobacter cloacae, Acinetobacter calcoaceticus, and Enterococcus faecalis. HR 810 was superior to cefuzonam (CZON) and cefmetazole against MRSA and MSSA and was much more active than any other antibiotics tested against E. cloacae and A. calcoaceticus. In the activity against E. faecalis, HR 810 was inferior to ampicillin but superior to CZON. In mice with pyelonephritis caused by E. coli Ec-7, the rank order of activities was HR 810 greater than CAZ greater than CTX greater than CPZ. HR 810 was more effective than latamoxef, CAZ, CTX, and CPZ in improving lung infections induced by Streptococcus pneumoniae HL 438 and Klebsiella pneumoniae Kp-51 in mice. HR 810 was superior to CTX and CPZ and comparable to cefazolin in therapeutic effects on intrauterine infections with E. coli Ec-89 and S. aureus SMITH in rats.     

Antibacterial activity of aztreonam: a synthetic monobactam. A comparative study with thirteen other antibiotics

The in vitro activity of aztreoman (SQ 26, 776), a new monocyclic beta-lactam antimicrobial agent, was determined against 1720 bacteria, all clinical isolates, and compared with that of thirteen beta-lactam and aminoglycoside antibiotics. Aztreonam inhibited 90% of Citrobacter diversus, Citrobacter freundii, Enterobacter agglomerans, E. coli, Klebsiella pneumoniae, Proteus mirabilis, Proteus morganii, Proteus rettgeri, Proteus vulgaris and Salmonella sp. by less than or equal to 0.4 micrograms ml-1. This activity was superior to moxalactam, piperacillin, cefamandole, cefoperazone, cefoxitin, cefsulodin, ceftazidime and aminoglycoside antibiotics. Aztreonam was as active as moxalactam against Enterobacter aerogenes, Enterobacter cloacae and Shigella species. Pseudomonas aeruginosa strains resistant to moxalactam, piperacillin, cefamandole, cefoperazone, cefotaxime, cefoxitin, cefsulodin and ceftazidime were inhibited by aztreonam 50% by 6.3 micrograms ml-1 and 90% by 16 micrograms ml-1. Aztreonam was as active as ceftazidime against Serratia marcescens, all strains were inhibited by 3.1 micrograms ml-1 and 90% by 1.6 micrograms ml-1. There was no major difference between MBC and MIC values of aztreonam and the effect of inoculum size upon MIC values was observed at 10(7) CFU.     

In vitro antibacterial activity of FK041, a new orally active cephalosporin.

The in vitro activity of FK041, a new orally active cephem antibiotic, against a wide variety of clinical isolates of bacteria was investigated and compared with those of cefdinir (CFDN) and cefditoren (CDTR). FK041 exhibited broad spectrum activity against reference strains of Gram-positive and Gram-negative aerobes and anaerobes. FK041 was active against clinical isolates of Gram-positive organisms except Enterococcus faecalis with MIC90s less than 1.56 microg/ml. FK041 was more active than CFDN and CDTR against Staphylococcus aureus, Staphylococcus epidermidis, and Streptococcus agalactiae and was comparable to CFDN and CDTR against Streptococcus pyogenes and Streptococcus pneumoniae. FK041 had no activity against methicillin-resistant staphylococci, like CFDN and CDTR. FK041 showed moderate activity against penicillin-resistant S. pneumoniae with an MIC range of 0.05 approximately 3.13 microg/ml, and was superior to CFDN but inferior to CDTR. Against clinical isolates of many Gram-negative organisms such as Neisseria gonorrhoeae, Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, FK041 had good activity comparable or superior to those of CFDN and CDTR. However, it was inferior to CDTR in activity against Moraxella catarrhalis, Haemophilus influenzae, Morganella morganii, and Serratia marcescens, and was inactive against Pseudomonas aeruginosa. With FK041 a small difference between MIC and MBC against S. aureus, E. coli, K. pneumoniae, and H. influenzae was found, indicating that its action is bactericidal against these species. FK041 was stable to group 2beta-lactamase hydrolysis but was unstable to group 1beta-lactamase hydrolysis. The stability of FK041 to these enzymes was similar to those of CFDN and CDTR. FK041 showed high affinity for the main penicillin-binding proteins (PBPs) of S. aureus (PBP 3, 2, and 1) and E. coli (PBP 3, 4, lbs, 2, and 1a).     

Antibacterial and pharmacokinetic properties of M14659, a new injectable semisynthetic cephalosporin

In vitro and in vivo antibacterial activities and pharmacokinetics of M14659 were investigated. In vitro activity of M14659 was superior to that of ceftazidime against Staphylococcus aureus. Against Gram-negative bacteria except Pseudomonas aeruginosa, its activity was almost equal to that of ceftazidime. M14659 was more active against P. aeruginosa including multi-drug resistant strains than cefsulodin, cefoperazone or ceftazidime. Affinities of M14659 for penicillin-binding proteins (PBPs) of Escherichia coli and P. aeruginosa were 2 to 14 times higher for PBP-1A and PBP-1B than found for ceftazidime, and almost the same for PBP-3. In vivo activity of M14659 against S. aureus was superior to that of cefamandole, cefotaxime or ceftazidime. Against Gram-negative bacteria including P. aeruginosa, M14659 was 2 to 220 times more active than cefotaxime or ceftazidime. Plasma half-life of M14659 in mice was about 3 times longer than that of ceftazidime. M14659 administered intravenously to mice was mainly excreted in urine without metabolism, and its recovery rate was almost equal to that of ceftazidime.     

Third-generation cephalosporins: comparative antibacterial activity against routine clinical isolates

The in vitro antibacterial activity of five third-generation cephalosporins (thienamycin, ceftazidime, cefotaxime, moxalactam and cefoperazone) was compared with that of three second-generation cephalosporins (cefoxitin, cefamandole and cefuroxime) against 313 routine clinical isolates. Thienamycin, ceftazidime, cefotaxime and moxalactam had superior activity against coliform bacilli compared to cefoxitin, cefamandole and cefuroxime. Only three cephalosporins (ceftazidime, thienamycin and cefoperazone) had significant activity against Pseudomonas aeruginosa. Both third-and second-generation cephalosporins had similar activity against gram-positive cocci, except for thienamycin, which was the most active cephalosporin against Staphylococcus aureus and Streptococcus faecalis. No single cephalosporin showed overall superiority in antibacterial activity, but thienamycin and ceftazidime were the most active against the range of bacteria tested.     

Comparative in vitro evaluation of BMY-28142, a new broad-spectrum cephalosporin, versus other beta-lactams against multiresistant gram-negative isolates

The in vitro activity of the new parenteral cephalosporin BMY-28142 was compared with that of cephalothin, cefoxitin, cefotaxime, ceftriaxone, moxalactam, aztreonam and ceftazidime, against a total of 374 recent multiresistant Gram-negative microorganisms of nosocomial origin. Against all species of Enterobacteriaceae resistant to the first- and second-generation cephalosporins, BMY-28142 had superior inhibitory activity than the newer beta-lactams tested, with intrinsic activity against E. coli and Pr. mirabilis slightly less than that of cefotaxime and ceftriaxone. BMY-28142 differed from the other beta-lactams mainly in being at least 16-fold more active against E. cloacae, while BMY-28142 and ceftazidime showed comparable activity against Ps. aeruginosa strains. Against strains of Ps. aeruginosa resistant to both BMY-28142 and amikacin, the combination of the two antibiotics proved to be synergistic in vitro.     

Bactericidal activity of biapenem against various bacteria

The bactericidal activity of biapenem (BIPM), a new carbapenem agent, against Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Serratia marcescens was compared with those of imipenem (IPM), panipenem (PAPM), meropenem (MEPM) and ceftazidime (CAZ). The bactericidal activity of BIPM against S. aureus was equal to those of IPM, PAPM and MEPM. Against E. coli and K. pneumoniae, BIPM showed higher bactericidal activity than IPM and PAPM. Against P. aeruginosa, BIPM showed excellent bactericidal activity campared with IPM. The killing speeds of BIPM and IPM were obviously the most rapid among four carbapenems. BIPM showed a strong bactericidal activity against 5 species of bacteria including P. aeruginosa.     

In vitro antibacterial activity of FK482, a new orally active cephalosporin

FK482 is a new orally active cephem antibiotic which offers some advantages over the commercially available oral beta-lactam antibiotics. It displayed a broad spectrum of activity in vitro against stock strains of Gram-positive and Gram-negative aerobes and anaerobes. FK482 was more active in vitro than cefixime (CFIX), cefaclor (CCL) or cephalexin (CEX) against clinical isolates of Gram-positive organisms such as methicillin-sensitive Staphylococcus aureus, coagulase-negative Staphylococci including Staphylococcus epidermidis and strains of the Streptococcus group. Moderate activity was found against methicillin-resistant S. aureus and Enterococcus faecalis. Against clinical isolates of many Gram-negative species, including opportunistic pathogens, FK482 had good in vitro activity similar or slightly inferior to that of CFIX but superior to that of CCL or CEX. However, it was clearly inferior to CFIX in activity against Serratia marcescens, and was inactive against Pseudomonas aeruginosa. Strains of S. aureus resistant to methicillin were moderately susceptible to FK482. All tested strains of Klebsiella pneumoniae resistant to CCL and CEX were susceptible to FK482, as were all the strains of Escherichia coli, Proteus mirabilis, Haemophilus influenzae and Branhamella catarrhalis resistant to amoxicillin (AMPC). FK482, like CFIX, was relatively stable to all type of beta-lactamases except Bacteroides fragilis and its stability was superior to that of CCL or CEX. The antibacterial activity of FK482 against CSH2 strains containing ampicillin-resistance plasmids was not affected by the presence of the ampicillin resistance determinants. FK482 showed higher affinity for the penicillin-binding proteins (PBPs) (3, 2 and 1) of S. aureus than did CFIX, CCL and CEX. FK482 also showed very high affinity for the PBPs (2 and 3) of E. faecalis and PBPs (3, 1a, 4, 2 and 1 bs) of E. coli. The bactericidal activity of FK482 against S. aureus was almost as strong as that of AMPC and superior to that of CCL or CEX. Against Gram-negative bacteria such as E. coli, K. pneumoniae and P. mirabilis, FK482 was similar to CFIX and superior to CCL and CEX in bactericidal activity.     

Comparison of in vitro antibacterial activities of new cephems against clinical organisms (isolated between June 1983 and January 1984)

We compared the in vitro antibacterial activities of ceftizoxime (CZX), cefotaxime (CTX), cefmenoxime (CMX), cefoperazone (CPZ), ceftazidime (CAZ), latamoxef (LMOX) and cefotetan (CTT) against 2,729 strains of 11 organisms freshly isolated from 10 medical institutions in Japan between June 1983 and January 1984 and obtained the following results: Against S. pyogenes, LMOX and CTT, which have the methoxy group at the 7 position, were less active than the other drugs. LMOX inhibited 80% of S. pyogenes at 0.78 micrograms/ml; CTT, at 1.56 micrograms/ml; but CZX and CTX inhibited 100% at 0.025 micrograms/ml or lower; CMX, at 0.05 micrograms/ml; and CPZ and CAZ, at 0.20 micrograms/ml. Against H. influenzae, E. coli, K. pneumoniae, P. mirabilis and indole-positive Proteus, these test antibiotics, especially CZX, CTX and CMX, which have the aminothiazolyl methoxyimino group, were potently active. Against S. marcescens CZX and CAZ were more active than the other drugs and against P. aeruginosa CAZ was more active than the other drugs. The test organisms did not tend to acquire resistance to these cephems when our results were compared with the results obtained at the development period.     

Antimicrobial activity of cefotiam against various clinical isolates from 1981 to 1985

Some of new cephem antibiotics, particularly the so called the third generation cephalosporins, are reported to be potent inducers of beta-lactamases and to be responsible for developing microbial cross-resistance to multiple beta-lactam antibiotics and occasionally to the aminoglycosides (Sanders and Sanders, 1983). In Japan, third generation cephalosporins such as cefotaxime, cefoperazone, ceftizoxime, and latamoxef became available in 1981, and cefmenoxime in 1982. Therefore, it is of interest to investigate changes, if any, in the antimicrobial activity of cefotiam (CTM) against various Gram-positive and negative bacteria, particularly to determine whether its antimicrobial activity has been reduced since 1982. Susceptibilities of clinical isolates of S. aureus (1,776 strains), S. epidermidis (2,247), S. pneumoniae (160), S. pyogenes (108), E. faecalis (1,930), E. coli (2,024), K. pneumoniae (1,913), Proteus spp. (950), E. aerogenes (823), Serratia marcescens (1,160), Citrobacter spp. (303), Pseudomonas aeruginosa (2,824), and H. influenzae (396) to CTM were studied. It was found that susceptibilities of these clinical isolates to CTM were not altered from 1981 to 1985, except S. marcescens. In 1985, susceptible strains of S. aureus, S. epidermidis, S. pneumoniae, S. pyogenes and E. faecalis were 93.8, 93.4, 100, 100 and 0%, respectively. Those of E. coli, K. pneumoniae, Proteus spp., H. influenzae, P. aeruginosa, S. marcescens, E. aerogenes and Citrobacter spp. were 97.9, 97.7, 89.4, 94, 0, 10.8, 45.9 and 74.5%, respectively. The rate of susceptible strains of S. marcescens decreased from 34.7 to 10.8% since 1981 to 1985.(ABSTRACT TRUNCATED AT 250 WORDS)     

In vitro antibacterial activity and beta-lactamase stability of cefodizime, a new cephalosporin antibiotic

The in vitro activity and beta-lactamase stability of cefodizime (HR 221), a new cephalosporin, were compared with those of other cephem antibiotics. HR 221 was highly active against Gram-negative bacteria. The compound inhibited growth of all tested Haemophilus influenzae strains at 0.10 microgram/ml and showed strong activity even against penicillin-resistant Neisseria gonorrhoeae strains, but it was less effective against Pseudomonas aeruginosa than the other antibiotics tested. Against Gram-positive bacteria, HR 221 showed 100% inhibition of growth of Streptococcus pneumoniae at 0.39 microgram/ml, and it was slightly less active against Staphylococcus aureus (MIC90:12.5 micrograms/ml) than other antibiotics such as cefotaxime (CTX). The bactericidal activity of HR 221 against E. coli was dose-related and comparable to that of CTX, cefoperazone and latamoxef. The bactericidal activity of the compound at medium concentrations simulating human serum levels was higher than that of CTX and cefmetazole, and no cell regrowth was noted after beta-lactamase-induced inactivation of the compound. HR 221 was stable to most drug-inactivating enzyme preparations from various bacterial species.     

In vitro activity of aztreonam, cefuroxime and ceftazidime against gram-negative rods isolated from hospital patients with urinary tract infection

The in vitro activity of aztreonam, cefuroxime and ceftazidime was determined against 2,372 Gram-negative rods (including Pseudomonas spp.) isolated from hospital patients with urinary tract infections during 1985. Minimum inhibitory concentrations (MICs) were determined using an agar incorporation technique in Mueller-Hinton agar. The inoculum used was approximately 10(5) colony forming units (cfu) contained in 10 microliter Mueller-Hinton broth, which was applied to the surface of the agar plates using a multipoint inoculator. Following inoculation plates were incubated aerobically at 37 degrees C for 18 h. The MIC of each antimicrobial for each organism examined was determined as the lowest concentration of the antimicrobial which completely inhibited growth of the inoculum. The minimum concentration required to inhibit the growth of 90% (MIC90) of the bacterial isolates in each genus or species examined was also determined. In general the antibacterial spectrum of aztreonam was comparable to that of ceftazidime and superior to that of cefuroxime. Against Escherichia coli, which accounted for 72% of the isolates examined, aztreonam (MIC90 less than or equal to 0.25 microgram/ml) was slightly more active than ceftazidime (MIC90 0.5 microgram/ml) and considerably more active than cefuroxime (MIC90 8 micrograms/ml). Aztreonam was active against Pseudomonas spp. (MIC90 16 micrograms/ml), although somewhat less so than ceftazidime (MIC90 4 micrograms/ml). Cefuroxime showed low activity against this genus (MIC90 greater than 128 micrograms/ml).     

Antimicrobial evaluation of cefoxitin: a new semisynthetic cephamycin. Comparative studies with cefazolin and cefalotin

Antimicrobial activity of 3-carbamoyloxymethyl-7-alpha-methoxy-7-[2-(2-thienyl)-acetamido]-3-cephem-4-carboxylic acid (cefoxitin), a new semisynthetic cephamycin antibiotic, was studied in comparison with that of cefazolin and cefalotin. Cefoxitin exhibited antibacterial activity against both gramnegative and gram-positive bacteria, and its action was bactericidal. Against gram-negative bacteria, cefoxitin was highly active as well as cefazolin, and more active than cefalotin. Especially, cefoxitin was highly active not only against strains of clinical isolates of indole-positive Proteus and S. marcescens but also against those of E. coli and P. mirabilis which were resistant to cefazolin and/or cefalotin, respectively. In addition, cefoxitin was effective against the strains resistant to beta-lactam antibiotics including cefazolin and cefalotin. Cefoxitin was hardly active against the strains of E. cloacae and P. aeruginosa, similar to cefazolin and cefalotin. Against gram-postive bacteria, cefoxitin was less active than cefazolin and cefalotin. In protection tests in mice, cefoxitin and cefazolin were more effective against infection with E. coli than cefalotin. Furthermore, cefoxitin was more active against infections with S. marcescens and P. morgani than the other antibiotics. Cefoxitin, like cefalotin, was less effective against infection with S. aureus than cefazolin. Cefoxitin was highly resistant to hydrolysis by beta-lactamases derived from the organisms insusceptible to the antibiotic. This fact revealed that the resistance of the organisms to cefoxitin may be in part due to factors other than beta-lactamase inactivation.     

2008年我院感染病原菌的分布及药物敏感性分析

目的分析院内感染病原菌的分布趋势及药物敏感性,为临床合理用药提供依据。方法药物敏感试验采用K—B纸片扩散法,以自行研制的院内感染监控系统软件进行数据统计分析。结果医院临床分离率居前10位的细菌分别为大肠埃希菌、金黄色葡萄球菌、铜绿假单胞菌、鲍曼不动杆菌、肺炎克雷伯菌、白假丝酵母、屎肠球菌、粪肠球菌、阴沟肠杆菌、表皮葡萄球菌。其中耐甲氧西林金黄色葡萄球菌（MRSA）的分离率已达到65．23％,产超广谱β-内酰胺酶（ESBLs）的大肠杆菌和肺炎克雷伯菌分别为58．20％和67．90％,革兰阳性（G^＋）球菌对万古霉素、替考拉宁的敏感率均保持在98％以上;肠杆菌科中大肠埃希菌、肺炎克雷伯菌、产酸克雷伯菌、阴沟肠杆菌对亚胺培南的敏感率均在90％以上;非发酵菌中铜绿假单胞菌和鲍曼不动杆菌敏感率最高的是头孢哌酮舒巴坦。结论万古霉素、替考拉宁对G^＋球菌始终保持着高活性,未发现万古霉素耐药的葡萄球菌;碳青酶烯类仍然是对肠杆菌科细菌活性最好的药物;非发酵菌中铜绿假单胞菌和鲍曼不动杆菌的耐药性不断增加,并出现了多重耐药菌株。     

In vitro and in vivo evaluations of BMY-28100, a new oral cephalosporin

A new semisynthetic oral cephalosporin, BMY-28100, was evaluated for in vitro and in vivo antibacterial activities in comparison with cefaclor and cephalexin. BMY-28100 showed in vitro activity 3- and 10-fold more potent than that of cefaclor against Staphylococcus aureus and Streptococcus pneumoniae, respectively. BMY-28100 was slightly better than cefaclor and about 4 times more active than cephalexin against Haemophilus influenzae and Neisseria gonorrhoeae. Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis were comparably susceptible to BMY-28100 and cefaclor. The bactericidal activity of BMY-28100 against S. aureus, E. coli and P. mirabilis was equal to or twice as high as MIC value, which was similar to that of cefaclor. The stability of BMY-28100 against penicillinases was nearly comparable to that of cefaclor, whereas cefaclor was somewhat unstable to cephalosporinases. BMY-28100 was about twice as active as cefaclor against three Gram-positive bacterial infections. BMY-28100 was also more potent against infections of H. influenzae and P. mirabilis, but slightly less active against E. coli Juhl than cefaclor. Blood level parameters of BMY-28100 were significantly superior to those of cefaclor and slightly better than cephalexin in mice and rats. The urinary recovery of BMY-28100 was somewhat higher and comparable to that of cefaclor and cephalexin, respectively. BMY-28100 was more stable than cefaclor in human and calf sera at 37 degrees C.     

Combined effect of sulbactam/cefoperazone and other antibiotics against clinical isolates of multi-resistant strains. I. Effect of sulbactam against beta-lactams resistant strains and in vitro combined effect of sulbactam/cefoperazone with each of piperacillin, latamoxef, ceftazidime, fosfomycin and doxycycline

We evaluated relationships between production of beta-lactamase and their resistances to beta-lactams, effect of sulbactam (SBT), a beta-lactamase inhibitor, against beta-lactam resistant strains, and combined effect of sulbactam/cefoperazone (SBT/CPZ) with other antibiotics against multi-resistant strains. Through these studies, we obtained the following results. 1. Most of the strains resistant to beta-lactams were beta-lactamase producers. 2. Relationships between the production of beta-lactamase and their resistances to beta-lactams indicate that their resistances generally were the highest in producers of both penicillinase (PCase) and cephalosporinase (CEPase), moderate in producers of either PCase or CEPase, and the lowest in beta-lactamase non-producers. Most of highly-resistant strains of MRSA appeared to be beta-lactamase non-producers though some exceptions were observed among methicillin-resistant Staphylococcus aureus (MRSA), Serratia marcescens and Pseudomonas aeruginosa. 3. SBT showed good effect against PCase producers, moderate effect against producers of both PCase and CEPase, little effect against CEPase producers, and no effect against beta-lactamase non-producers. 4. Results of combined effect of SBT/CPZ with other antibiotics indicated that good synergism was obtained by combining SBT/CPZ with fosfomycin (FOM) or piperacillin against multi-resistant strains of Proteus spp., Enterobacter cloacae, and S. marcescens, by combining SBT/CPZ with ceftazidime (CAZ) or FOM in methicillin-sensitive S. aureus and by combining SBT/CPZ with CAZ in P. aeruginosa. 5. Better synergism was obtained with the higher concentrations of antibiotics.     

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.     

In vitro studies on dosing interval of cefoperazone (author's transl)

Serum pharmacokinetics of 1 g cefoperazone was simulated in vitro. Initial concentration was 190 microgram/ml, half-life 128 min. Bactericidal activity and regrowth interval was determined against 17 clinical isolates. Rapid initial killing was seen especially against E. coli, K. pneumoniae and E. cloacae and with some reservations also against P. aeruginosa. The bactericidal activity was slower against P. mirabilis and S. aureus. Only 8 out of 17 tested strains regrew to 1% mark between 8.5 and 12 h after exposure to cefoperazone was started. The regrowth interval ranged from 0.5 to 6.5 h.     

In vitro activity of aztreonam against gram negative bacteria from clinical specimens and its comparison with other commonly used antibiotics

A total of 755 gram negative bacteria isolated from clinical specimens were tested against aztreonam by the disc agar diffusion test. The strains of bacteria used in this study consisted of Escherichia coli (314), Enterobacter aerogenes (30), E. agglomerans (7), E. cloacae, (39), Citrobacter diversus (9), C. freundii (13), Hafnia alvei (3), Acinetobacter calcoaceticus (10), Klebsiella oxytoca (6), K. ozaenae (5), K. pneumoniae (107), Morganella morganii (3), Moraxella sp. (10), Pasteurella multocida (1), Proteus mirabilis (66), P. vulgaris (4), Providencia rettgeri (12), P. stuartii (5), Pseudomonas aeruginosa (85), P. fluorescens (2), P. maltophila (7), Salmonella sp. (1) and Serratia marcescens (17). In vitro activity against aztreonam was compared with amikacin, ampicillin, carbenicillin, cephalosporin, cefoxitin, chloramphenicol, gentamicin, nitrofurantoin, piperacillin, tetracycline, sulfamethoxazole-trimethoprim and tobramycin. Over 99% of E. coli and Enterobacter species were susceptible to aztreonam. All the 118 strains of Klebsiella, 87 strains of Proteus-Providencia and 17 strains of S. marcescens were also susceptible. Aztreonam also showed good activity against P. aeruginosa, inhibiting 90% of the 85 isolates tested.     

Laboratory and clinical studies of sulbactam/cefoperazone in the pediatric field

The authors have carried out the laboratory and clinical studies of sulbactam/cefoperazone (SBT/CPZ) and obtained the following results. The antibacterial activities of SBT/CPZ against the clinical isolates of S. aureus, E. coli, K. pneumoniae, E. cloacae, E. aerogenes, S. marcescens, P. aeruginosa were measured by the plate dilution method with inoculum size of 10(6) cells/ml. The susceptibility distribution of S. aureus to SBT/CPZ ranged from 0.39 to 6.25 micrograms/ml, and the peak of distribution was 1.56 micrograms/ml. The peak of susceptibility distribution of K. pneumoniae was 0.20 microgram/ml, and the distribution of E. coli and E. aerogenes ranged from 0.10 to 12.5 micrograms/ml and that of S. marcescens, from 0.2 to 25 micrograms/ml. The growth of 80.8% of P. aeruginosa was inhibited at the concentration of 12.5 micrograms/ml. The distribution of E. cloacae ranged from 0.1 to 50 micrograms/ml. For pharmacokinetic study, SBT/CPZ was given in a single dose of 20 mg/kg by drip infusion for 1 hour in 2 children and 40 mg/kg by drip infusion for 1 hour in 1 children. With drip infusion of SBT/CPZ, the peak serum level were 17.8/43.9 micrograms/ml, 21.8/75.5 micrograms/ml on completion of the infusion, respectively. SBT/CPZ was effective in 14 cases out of 16 cases with clinical effect. No side effect was observed except for eosinophilia in 1 case.