Bactericidal activity of biapenem against various efflux system mutants of Pseudomonas aeruginosa

The bactericidal activity of biapenem, a new carbapenem, against various efflux-mutants of Pseudomonas aeruginosa was compared with those of imipenem, panipenem, meropenem and ceftazidime. The bactericidal activity of biapenem against P. aeruginosa KG5001, a strain deficient in MexAB-OprM, MexCD-OprJ and MexXY-OprM, was very strong compared with those of imipenem and meropenem. In terms of bactericidal activities, biapenem and imipenem had similar activities against P. aeruginosa KG5003, a strain overexpressing MexAB-OprM, as against P. aeruginosa KG5001, however meropenem and ceftazidime had weaker activities against KG5003 than KG5001. The bactericidal activity against P. aeruginosa KG5007, a strain overexpressing MexCD-OprJ, was observed only by biapenem. The bactericidal activity of biapenem was strong and not influenced by all of these three efflux systems.     

Bactericidal activity of various antibiotics against biofilm-producing Pseudomonas aeruginosa

Clinical isolates of Pseudomonas aeruginosa were collected from hospitals in Tehran, Iran, and identified using biochemical tests. A modified microtitre plate test was used to determine the biofilm-forming capacity of the isolates, measured with an enzyme-linked immunosorbent assay (ELISA) reader. Results showed that P. aeruginosa strain 214 was the most efficient at producing biofilm compared with the other strains. Observation of the bacterial biofilm on Teflon sheets and on a catheter using a scanning electron microscope showed greater biofilm formation on the catheter than on Teflon sheets. In this study, we investigated the bactericidal activity of fluoroquinolones, beta-lactams, macrolides and aminoglycoside. The results showed differences in the antibiotic susceptibility of planktonic and biofilm cell populations. Fluoroquinolones showed more potent activity than the other antibiotics, and biofilms were completely eradicated by treatment with 16 x the minimum inhibitory concentration (MIC) of ciprofloxacin and 64 x MIC of ofloxacin, whereas all biofilms survived 2560 microg/mL of imipenem and ceftazidime. Production of an exopolysaccharide matrix is one of the distinguishing characteristics of biofilms. It has been suggested that this matrix prevents access of antibiotics to the bacterial cells embedded in the community. In this study, we also evaluated the permeation of antibiotics through alginate of P. aeruginosa strain 214 using a sandwich cup method. Macrolides were most efficient, showing 100% penetration; fluoroquinolones and beta-lactams had a high permeation rate > 75%, whereas the rates for aminoglycosides were low (amikacin = 59%; gentamicin = 73%).     

Antibacterial activity of biapenem against recent clinical isolates

Antibacterial activity of biapenem (BIPM) against clinical isolates of 8 species between 2000 and 2002 was compared with those of imipenem/cilastatin (IPM/CS), meropenem (MEPM), panipenem/betamipron (PAPM/BP) and ceftazidime (CAZ). The MICs of biapenem for Gram-positive bacteria were higher than those of IPM/CS and PAPM/BP, equal to those of MEPM and lower than those of CAZ. The MICs of BIPM for Gram-negative bacteria were higher than those of MEPM, equal to those of IPM/CS and PAPM/BP, and lower than those of CAZ. Antibacterial activity of BIPM against Pseudomonas aeruginosa was equal to those of IPM/CS and MEPM and superior to those of PAPM/BP and CAZ. In conclusion, BIPM showed broad antibacterial activity against both Gram-positive and Gram-negative clinical isolates. These results suggest that BIPM is useful for the treatment of various bacterial infections.     

Bactericidal activity of ertapenem against major intra-abdominal pathogens

Treatment of intra-abdominal infections remains a challenge owing to their polymicrobial nature and associated mortality risk. Treatment regimens must provide broad-spectrum coverage, including Gram-positive and Gram-negative aerobic and anaerobic bacteria of gastrointestinal origin. Ertapenem is a long-acting 1-beta-methyl parenteral group 1 carbapenem antibiotic that has a broad antibacterial spectrum and once-daily dosing supported by clinical studies. It is active against Gram-positive and Gram-negative bacteria, including Enterobacteriaceae, Streptococcus pneumoniae and most species of anaerobic bacteria. The aim of this study was to measure the killing effects of ertapenem against a selected group of strains responsible for intra-abdominal infections. Gram-negative isolates comprised the following species: Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Klebsiella ozaenae, Enterobacter cloacae and Proteus mirabilis (extended-spectrum beta-lactamase (ESBL) producers and non-producers). Gram-positive isolates comprised methicillin-susceptible Staphylococcus aureus (MSSA), Enterococcus faecalis and anaerobic Bacteroides fragilis. Ertapenem activity was tested by determination of minimal inhibitory concentrations (MICs) and minimal bactericidal concentrations (MBCs). Killing curves were performed in monocultures and co-cultures at selected antibiotic concentrations. Ertapenem showed a rapid and potent bactericidal activity in the first few hours of the kinetic curves against E. coli (6 log(10) colony-forming unit (CFU) reduction in the first 2h), B. fragilis (4 log(10) CFU reduction in 4h), MSSA (3 log(10) CFU reduction in 4-6h), K. ozaenae (ESBL+), K. pneumoniae (ESBL+ and -), E. cloacae (ESBL-) in 1h and P. mirabilis (ESBL+) in the first 2h. The potent bactericidal activity of ertapenem compared with ceftriaxone and piperacillin/tazobactam was well demonstrated in the co-cultures of E. coli-B. fragilis and E. coli-B. fragilis-E. faecalis, whilst ertapenem was shown to be bactericidal at 24h in the mixed culture of S. aureus-P. mirabilis. These results support the potent in vitro bactericidal activity of ertapenem against all multiresistant strains selected in this study and the use of this drug in the treatment of intra-abdominal infections.     

比阿培南等10种抗菌药物对常见革兰阴性杆菌体外抗菌活性比较

目的:评价比阿培南等10种抗菌药物对临床分离革兰阴性杆菌的体外抗菌活性。方法:采用琼脂对倍稀释法测定比阿培南、厄他培南、亚胺培南、美罗培南等10种抗菌药物对临床分离革兰阴性杆菌的最低抑菌浓度,所有数据用WHONET 5. 6进行分析比较。结果:比阿培南对于肠杆菌科中的大肠埃希菌、非CR-肺炎克雷伯菌、其他肠杆菌科细菌均显示出良好的抗菌活性,比阿培南的MIC₅₀和MIC₉₀与美罗培南相似,敏感率(97. 8%,100%,88. 2%)与美罗培南相似,优于亚胺培南和厄他培南。对于CR-肺炎克雷伯菌,比阿培南的敏感率(20. 6%)高于其他抗菌药物,MIC₅₀和MIC₉₀等于或低于美罗培南。对于非发酵菌中的不动杆菌属比阿培南的敏感率(40. 9%)低于头孢哌酮舒巴坦(50%)和阿米卡星(50%),优于环丙沙星(27. 3%),与其他碳青霉烯类抗菌药物相似(40. 9%),比阿培南的MIC₅₀和MIC₉₀与美罗培南及亚胺培南相似。对于铜绿假单胞菌比阿培南的敏感率(...     

Clinical evaluation of biapenem in various infectious diseases

The clinical usefulness of injectable biapenem (BIPM) was examined for various infectious diseases in the fields of internal medicine, urology, surgery, orthopedics, obstetrics and gynecology, otorhinolaryngology, ophthalmology, dermatology, oral surgery, and plastic surgery. BIPM was administered by intravenous drip infusion at a dose of 150, 300, or 600 mg twice a day. The concentrations in various body fluid and tissues were also examined. 1. In the total enrollment of 256 cases, the numbers subjected to the analyses for clinical efficacy, bacteriological efficacy, side effects and abnormal laboratory findings were 214, 170, 252 and 251 cases, respectively. 2. The clinical efficacy rate was 85.5% (183/214 cases) as a whole, being 2/2 for sepsis, 6/8 for cellulitis and lymphangitis, 76.2% (16/21) for traumatic, operative wound and burn infections, 4/6 for osteomyelitis and arthritis, 92.9% (13/14) for peritonsillar abscess and peritonsillitis, 83.3% (15/18) for chronic lower respiratory tract infection, 7/7 for pneumonia, 83.3% (30/36) for complicated urinary tract infection, 100% (14/14) for cholecystitis and cholangitis, 88.2% (15/17) for peritonitis, 86.5% (32/37) for internal genital infection, 8/9 for pelvic peritonitis, 2/4 for corneal ulcer, orbital infection and panophthalmitis, 1/2 for otitis media, 4/4 for sinustitis, 93.3% (14/15) for osteitis of jaw and cellulitis of mouth floor. The efficacy rate in the poor responders to the pretreatment by other antibiotics was 86.4% (70/81). 3. 300 strains of causative organisms were isolated from 170 cases which contained polymicrobial infections. The elimination rate of causative organisms was 85.3% (256/300 strains), in terms of bacteriological efficacy. 4. Side effects were noted in 11 of 252 cases (4.4%) with 11 events. The signs and symptoms were the skin symptoms (5 cases), gastro-intestinal symptoms (3 cases), interstitial pneumonia (2 cases), and feeling bad (1 case), all of which disappeared during treatment or after the discontinuation of treatment. The abnormal laboratory findings were observed in 31 of 251 cases (12.4%) with 50 events, and major ones were an increase in eosinophils, and elevations of AST, ALT, gamma-GTP and Al-p. 5. The concentrations of BIPM in body fluid and tissues were determined in 46 cases (212 samples) most of which were administered 300 mg of BIPM by intravenous drip infusion for 60 minutes. The concentrations in the sputum within 6 hours after administration were 0.1-2.5 micrograms/g. The maximum concentrations in body fluid and tissues were 0.2-1.8 micrograms/g or ml in the bile, middle ear mucosa, tonsillar tissue, aqueous humor and bone tissues and were 2.0-5.7 micrograms/g or ml in the gallbladder, maxillary sinus mucous membrane, ethmoidal sinus mucous membrane, oral tissues, skin, woman genitals, synovia, joint tissue, and the eschar. The concentrations in the uterine arterial plasma and retroperitoneal fluid were almost similar to those in the cubitl vein plasma. From the above-mentioned results of clinical efficacy, bacteriological efficacy, and safety, injectable BIPM was confirmed to be useful in the treatment of moderate, severe and/or refractory infections in various fields.     

Bactericidal activity of lemon juice and lemon derivatives against Vibrio cholerae

Food products can be possible vectors of the agent responsible for cholera epidemics, because some of these products allow Vibrio cholerae O1 to develop to concentrations above the dangerous level. This study deals with the behaviour of essential oils, natural and concentrated lemon juice and fresh and dehydrated lemon peel against V. cholerae O1 biotype Eltor serotype Inaba tox+. Our aim was to evaluate whether these products, used at different dilutions, exhibit bactericidal or bacteriostatic activity against the microorganism, when present at concentrations of 10(2), 10(4), 10(6) and 10(8) colony forming units (CFU) ml(-1), and after different exposure times. 10(8) CFU ml(-1) was considered an infectious dose. Concentrated lemon juice and essential oils inhibited V. cholerae completely at all studied dilutions and exposure times. Fresh lemon peel and dehydrated lemon peel partially inhibited growth of V. cholerae. Freshly squeezed lemon juice, diluted to 10(-2), showed complete inhibition of V. cholerae at a concentration of 10(8) CFU ml(-1) after 5 min of exposure time; a dilution of 2 x 10(-3) produced inhibition after 15 min and a dilution of 10(-3) after 30 min. It can be concluded that lemon, a natural product which is easily obtained, acts as a biocide against V. cholerae, and is, therefore, an efficient decontaminant, harmless to humans.     

利奈唑胺与万古霉素对耐甲氧西林金黄色葡萄球菌体外抗菌活性

目的 评价利奈唑胺(嗯唑烷酮类抗菌药)、万古霉素(胺基糖苷类抗生素)2种抗菌药物对耐甲氧西林金黄色葡萄球菌(MRSA)的体外抗菌活性.方法 用琼脂二倍稀释法,测定抗菌药物的最低抑菌浓度(MIC);用肉汤稀释法,测定抗菌药物的最低杀菌浓度(MBC),绘制杀菌曲线(KCs).结果 利奈唑胺对临床分离的98株MRSA的MIC50为1 μg·mL-1,MIC90为2 μg·mL-1,MBC50为8 μg·mL-1,MBC90为32 μg·mL-1,敏感率为100%;万古霉素对临床分离的98株MRSA的MIC50为1 μg·mL-1,MIC90为1 μg·mL-1,MBC50为8 μg·mL-1,MBC90为32 μg·mL-1,敏感率为100%.随着抗菌药物浓度的升高,其杀菌时间缩短不甚明显,呈现非浓度依赖性的特点.结论 利奈唑胺对MRSA的体外抗菌活性与万古霉素相当,均显示非浓度依赖性的杀菌曲线.     

Bactericidal activity of imipenem compared to erythromycin against intracellular Legionella pneumophila.

Pneumonia is the leading cause of death due to nosocomial infections with mortality ranging from 30 to 70%. Because imipenem has potent in vitro activity against virtually all major causes of nosocomial pneumonia, including P. aeruginosa, S. aureus, members of the family Enterobacteriaceae, and anaerobic organisms, it is used by many physicians as the empirical therapy of choice in severe nosocomial pneumonias. Recognition of Legionella species as nosocomial pathogens has been increasing. The incidence of Legionnaires' disease among patients with nosocomial pneumonia is reported to be as high as 30% (1), but the real prevalence is unknown. Imipenem has bactericidal activity against Legionella in vitro but has not previously been tested for efficacy against intracellular Legionellae.     

比阿培南对医院常见感染菌的抗菌活性分析

目的：调查新药比阿培南对我院,临床分离的常见致病菌的抗菌活性,为临床用药提供依据。方法：收集我院临床分离的135株共7类常见致病菌,采用K—B纸片琼脂扩散法,并设对照组：美罗培南组和亚胺培南组,结果判定参照NCCLS 2006年标准。结果：135株致病菌对比阿培南的药物敏感率为86．6％,对照组：美罗培南为49．6％、亚胺培南为46．2％。比阿培南对铜绿假单胞菌和不动杆菌属的敏感率分别为85％和50％,而美罗培南为50％和20．8％,亚胺培南为40％和8．3％。结论：新药比阿培南的抗菌活性明显高于同类碳青霉烯类抗生素美罗培南和亚胺培南,尤其在对铜绿假单胞菌和不动杆菌属细菌的敏感度上,新药比阿培南更具抗菌活性。     

比阿培南与其他抗菌药物对某院临床分离致病菌的体外敏感性比较

目的:比较研究比阿培南和其他抗菌药物的体外抗菌活性。方法:收集2015年1-5月某院分离的344株临床常见致病菌,采用纸片扩散法测定比阿培南和对照药(美罗培南、亚胺培南、厄他培南、氨曲南、左氧氟沙星、哌拉西林他唑巴坦、头孢他啶和头孢吡肟)对革兰阴性菌的敏感性,及比阿培南和对照药(美罗培南、左氧氟沙星、万古霉素、利奈唑胺、克林霉素、青霉素和呋喃妥因)对革兰阳性菌的敏感性。结果:比阿培南与美罗培南、亚胺培南、厄他培南、哌拉西林他唑巴坦对产和不产ESBL的大肠埃希菌和肺炎克雷伯菌、阴沟肠杆菌及其他肠杆菌的敏感率相仿,且差异无统计学意义(P>0.05),但比阿培南对铜绿假单胞菌的敏感率显著高于其他抗菌药物(P<0.05);比阿培南与美罗培南对甲氧西林敏感的金葡菌、耐甲氧西林的金葡菌、粪肠球菌和屎肠球菌的敏感率相仿,但显著低于万古霉素、利奈唑胺和呋喃妥因(P<0.001)。结论:与其他抗菌药物相比,比阿培南对某院临床分离的革兰阴性菌尤其是铜绿假单胞菌有较高的敏感率,但对鲍曼不动杆菌和肠球菌有较高的耐药率。     

Antibacterial activity of MT-141 against anaerobic bacteria

In vitro and in vivo antibacterial activities of MT-141, a new cephamycin, against anaerobic bacteria were compared with those of cefmetazole (CMZ), cefoxitin, cefotaxime, ceftizoxime, latamoxef and cefazolin to obtain the following results. MT-141 showed high activity against a wide variety of anaerobic bacteria including B. fragilis and C. difficile except for Eubacterium lentum, E. aerofaciens and B. furcosus. Antibacterial activity of MT-141 against anaerobic bacteria was almost independent of inoculum size, medium, pH and serum addition. In vitro development of resistance of MT-141 against P. variabilis and B. fragilis was comparable to that of CMZ. Successive parenteral administration of MT-141 into mice did not cause abnormal proliferation of C. difficile. MT-141 showed excellent therapeutic effect against experimental subcutaneous abscess in mice caused by B. fragilis.     

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.     

Contact imidazole activity against resistant bacteria and fungi

The activities of miconazole and miconazole sulphosalicylate were evaluated by a contact test using strains of Enterococcus faecalis and Escherichia coli and Candida spp selected for their resistance. The results showed that killing of the organisms occurred within a few minutes. Imidazole activity required a medium of low electrical conductivity and a pH of 5.6. Greater sensitivity could be obtained with pretreatment of the microbial suspensions with sodium dioctylsulphosuccinate. Microorganisms tested in culture media with low electrical conductivity and at pH 5.6 showed enhanced sensitivity to azoles with MIC values about 20-30 times lower than those obtained using control media. Practical implications of the use of topical drugs are discussed.     

Bactericidal activity against meticillin-resistant Staphylococcus aureus of a novel eukaryotic therapeutic recombinant antimicrobial peptide

Antimicrobial peptides (AMPs) are one of several potential antibacterial agents in the current era of antibiotics facing severe challenges. In this study, the bactericidal activity and stability of two eukaryotic AMPs were determined. Both AMPs showed specific antibacterial activity in a HEK293T cell model infected with meticillin-resistant Staphylococcus aureus. The recombinant eukaryotic AMP pVAX1/hBD3-CBD showed better bactericidal activity and stability than the eukaryotic AMP pVAX1/hBD3. These results illustrate that this peptide, designed and used with eukaryotic expression and recombinant methods, should be studied and applied in further AMP research and trials.     

In vitro activity of imipenem against gram-positive anaerobic bacteria

The in vitro activity of imipenem, a new penem antibiotic, was determined against 210 clinical Gram-positive anaerobic isolates and compared with the activities of metronidazole, clindamycin, cefoxitin, moxalactam, ceftizoxime, ceftriaxone and cefotiam. All investigated strains were inhibited by a 4-mg/l concentration of imipenem. Cefoxitin demonstrated good activity against most strains with exception of some Clostridium difficile and Clostridium ramosum strains. Cephalosporins were classed in decreasing activity order as follows: cefoxitin moxalactam ceftriaxone ceftizoxime cefotiam. Metronidazole had better activity against Clostridium spp. than against non-sporulated bacilli. Clindamycin resistance rates were superior to 10% for most groups, with the exception of Clostridium perfringens. Actinomyces and Bifidobacterium. Imipenem was the most potent inhibitor, as 81% and 95% of tested strains were inhibited at concentrations of 0.25 and 0.5 mg/l respectively.