Pharmacokinetic interaction of aztreonam with other antibiotics

The pharmacokinetic interaction of the monobactam antibiotic aztreonam with cephradine, clindamycin, gentamicin, metronidazole, and nafcillin was investigated in five separate studies in 48 healthy male volunteers. All drugs were administered by 30-minute intravenous infusions in single-dose, three-way balanced cross-over studies. Drug levels were measured in serum, protein-free filtrate of serum, and urine. Small changes of no clinical significance were seen when aztreonam was given simultaneously with another antibiotic as compared with each drug alone. Maximum serum concentrations of aztreonam were reduced by 12.6 and 9.8 per cent when it was given with gentamicin and metronidazole, respectively. The percentage of serum aztreonam bound to protein fell by a maximum of 5.0 per cent when the monobactam was given in conjunction with nafcillin and rose by 5.1 per cent when accompanied by cephradine. Twenty-four-hour cumulative urinary excretion of aztreonam and clindamycin rose by 5.2 and 10.9 per cent, respectively, when they were administered simultaneously.     

Antibacterial activity of 5-acylaminothiazole derivatives, synthetic drugs related to beta-lactam antibiotics

Newly synthesized 5-acylaminothiazolium salts and one 5-acylaminothiazolidine, considering their chemical structure and reactivity, have been proposed as potential inhibitors of bacterial serine DD-peptidases. A moderate antibiotic activity with (5-phenylacetylamino-3-thiazolio)acetate and (5-phenylacetylaminothiazolidin-3-yl)acetic acid was observed on Staphylococcus aureus ATCC 25923. The methyl- and tert-butyl esters of the thiazolium salt have shown lower MIC values. Moreover, when introduced into an exponential growth phase culture of S. aureus, the three active thiazolium salts induced a partial lysis indicating an impairing of the bacterial cell wall biosynthesis. The observed time-dependent binding of the best compound to the PBPs of S. aureus was too slow and occurred at too high concentrations to account for its MIC value. Consequently, the antibiotic activity of the thiazolium salts on the S. aureus cells seems not to be satisfactorily explained by a penicillin-like interaction with the PBPs.     

Ocimum basilicum: Antibacterial activity and association study with antibiotics against bacteria of clinical importance

Context: Ocimum basilicum L. (Lamiaceae), popularly known as basil, is part of a group of medicinal plants widely used in cooking and known for its beneficial health properties, possessing significant antioxidant effects, antinociceptive, and others.

Objective: The objective of this study is to determine the pharmacological effects produced on the bacterial strains Staphylococcus aureus and Pseudomonas aeruginosa when standard antibiotics and O. basilicum essential oil are combined.

Materials and methods: The extraction of O. basilicum (leaves) components was done by steam distillation. The Minimum inhibitory concentration (MIC) was calculated using microdilution technique, where the oil concentrations varied from 2 to 1024?μg/mL. The combinations of O. basilicum oil with ciprofloxacin or imipenem were analyzed by the checkerboard method where fractional inhibitory concentration (FIC) indices were calculated.

Results: Ocimum basilicum essential oil, imipenem, and ciprofloxacin showed respective MIC antibacterial activities of 1024, 4, and 2?μg/mL, against S. aureus. In S. aureus, the oil with imipenem association showed synergistic effect (FIC?=?0.0625), while the oil with ciprofloxacin showed antagonism (FIC value?=?4.25). In P. aeruginosa, the imipenem/oil association showed additive effect for ATCC strains, and synergism for the clinical strain (FIC values?=?0.75 and 0.0625). The association of O. basilicum essential oil with ciprofloxacin showed synergism for clinical strains (FIC value?=?0.09).

Conclusion: Ocimum basilicum essential oil associated with existing standard antibiotics may increase their antibacterial activity, resulting in a synergistic activity against bacterial strains of clinical importance. The antibacterial activity of O. basilicum essential oil may be associated with linalool.     

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.     

Antibacterial activity of human pleural fluid: alone and in combination with antibiotics.

This study investigated the antibacterial activity of human pleural fluid (HPF) and its interaction with gentamicin (GM), meropenem (MRPM), ciprofloxacin (CPFX) and clarithromycin (CLTM) against Escherichia coli K-12, Proteus rettgeri (Sanelli) and Staphylococcus aureus. Minimal inhibitory concentrations or volumes, expressed as MIC or volume percentage (MIV, V/V%), were measured using a micro-dilution technique in microtiter plates. The antimicrobial activity of HPF combinations with antimicrobial drugs was evaluated by the chequerboard method calculating the fractional inhibitory concentration index (FIC) values. HPF MIVs (%) were: 37.54; 19.85; 1.74 for E. coli, P. rettgeri and S. aureus, respectively. FIC values indicated a synergistic effect with GM, MRPM and CPFX against E. coli and P. rettgeri and an additive effect for the combination HPF plus CLTM or indifference with HPF plus GM and CPFX against S. aureus. The presence of antibodies, complement factors, lysozyme, -defensins and enzymes could explain the antimicrobial activity of HPF and its synergistic effect with certain antibiotics.     

A comparative study of the hemolytic effect of polyenic antibiotics and of other cholesterol-binding agents

Macrocyclic polyenic antibiotics were compared, on the basis of their hemolytic efficiency (expressed as critical occupancy level and as mean intrinsic association constant) with each other and with other cholesterol-specific hemolytic agents, such as digitonin and streptolysin O.In all cases, except for the larger polyenic antibiotics (amphotericin B and nystatin), the experimental results were compatible with the existence in the membrane of a large number of identical binding sites which are independent from each other.Simultaneous addition of two different agents gave either synergistic or antagonistic effects, indicating that digitonin, streptolysin O and filipin have different mechanisms of action from each other and from the mycosamine-containing polyenes.     

Antibacterial activity of N-formimidoyl-thienamycin in comparison with other beta-lactam antibiotics against clinical problem strains (author's transl)

The efficacy of N-formimidoyl-thienamycin (MK 0787) has been tested against 549 cultures of different species, which often cause therapeutic problems. Included were 286 mezlocillin-resistant strains, 100 Serratia marcescens and 66 Pseudomonas aeruginosa. The minimal inhibitory concentration ranged between 0.06 and 4 micrograms/ml by means of the agar-dilution-method. Resistant strains were not observed. Among the 11 beta-lactam- and aminoglycoside-antibiotics tested N-formimidoyl-thienamycin was the most effective with the broadest spectrum.     

The antibacterial activity of new cephem antibiotics against clinical isolates. A comparison of the antibacterial activity of cefotaxime with 6 other antibiotics

During the period from May through July 1981, a comparative study was carried out on the antibacterial activities of cefotaxime (CTX) and ceftizoxime (CZX), cefoperazone (CPZ), latamoxef (LMOX), cefotiam (CTM), cefmetazole (CMZ) and cefazolin (CEZ). CTX and these other cephem antibiotics were tested against fresh clinical isolates which had been obtained from clinical materials by the laboratories of 14 participating medical institutions. 1. The clinical isolates were obtained from various clinical materials in the following decreasing order: urine, sputum and pus/discharge; 85.7% of the isolates came from these materials. 2. Concerning the sources of each species of clinical isolates, it was found that P. aeruginosa was isolated from the greatest number -9- of different clinical materials. This was followed by E. coli and E. cloacae, each isolated from 8 different clinical materials, and C. freundii and E. aerogenes, each found in 7 different clinical materials. 3. In relation to S. pyogenes, S. agalactiae and S. pneumoniae, CTX showed the best antibacterial activity; the second most potent antibiotic was CZX. CMZ and LMOX were found to show relatively high MIC values for those species. Against S. aureus, CEZ showed the best antibacterial activity, but 3 resistant strains had MICs of greater than 100 micrograms/ml. 4. With regard to Gram-negative bacteria, CTX and CZX showed the best antibacterial activities for all of the species, except for P. aeruginosa. These were followed, in order, by LMOX and CPZ. Compared with these 4 antibiotics, CTM, CMZ and CEZ were found to have inferior antibacterial activities against these bacteria. In relation to P. aeruginosa, the peak of the MIC distribution for CPZ was 6.25 micrograms/ml, and this was the best antibacterial activity detected with the various antibiotics tested. This was followed by CTX (25 micrograms/ml) LMOX (25 micrograms/ml) and CZX (50 micrograms/ml). CTM had an MIC of 100 micrograms/ml for 1 strain, and MICs of greater than 100 micrograms/ml for all of the other strains of P. aeruginosa, indicating them to be resistant to this antibiotic. All of the strains were resistant to CMZ and CEZ, showing MICs of greater than 100 micrograms/ml. 5. For each of the tested antibiotics, no correlation was found between the MIC and the serogroup for either P. aeruginosa or S. marcescens.     

碳青霉烯类抗生素对铜绿假单胞菌抗菌活性的检测

目的 探讨铜绿假单胞菌(PA)临床分离株对碳青霉烯类抗生素耐药性与其产AmpCβ内酰胺酶(AmpC酶)的关系.方法 收集并鉴定PA临床分离株,采用头孢西丁敏感试验对产AmpC酶的菌株进行初筛.运用Kirby-Bauer纸片扩散法、固体培养基连续稀释法检测头孢菌素类与碳素霉烯类抗生素对PA筛选菌株的抗菌活性.采用三维确认试验检测碳青霉烯类抗生素耐药菌株产生AmpC酶的情况.结果 PA筛选菌株对头孢呋肟钠(CXM)、头孢噻甲羧肟(CAZ)、头孢噻肟钠(CTX)、头孢哌酮钠(CFP)及盐酸头孢吡肟(FEP)的耐药率分别为100%、36.3%、63.6%、54.5%、22.7%;对亚胺培南(IPM)、帕尼培南(ETP)、美罗培南(MEM)的耐药率分别为40.9%、45.0%、18.1%,部分菌株对所有试验用药均耐药.IPM、ETP、MEM对PA筛选菌株的最低抑菌浓度(MIC)均≥19 μg/ml,且各试药的最低杀菌浓度(MBC)值与MIC值相差较大,约36.0%菌株的MBC是MIC的16～32倍.约22.6%菌株检测出产生AmpC酶.结论 我市医院近半年来收集的PA对第4代头孢菌素类抗生素FEP具有较高的敏感性;对临床用碳青毒烯类抗生素MEM的敏感性明显高于IPM与ETP,但有较大比例的耐药菌株出现;部分菌株耐药性形成可能与其产生AmpC酶有关系.     

Antibacterial activity of 16 antibiotics against Helicobacter pylori

The susceptibilities of 24 Helicobacter pylori isolates, which were originated from clinical materials, to 5 beta-lactam antibiotics [benzylpenicillin (PCG), ampicillin (ABPC), cephalothin (CET), ceftazidime (CAZ), cefotiam (CTM) and imipenem (IPM)], two macrolides [clarithromycin (CAM) and rokitamycin (RKM)], two aminoglycosides [amikacin (AMK) and gentamicin (GM)], two new quinolones [ciprofloxacin (CPFX) and levofloxacin (LVFX)], two tetracycline [tetracycline (TC) and minocycline (MINO)], rifampicin (RIF) and chloramphenicol (CP) were tested. All of the isolates showed similar susceptibilities against beta-lactam antibiotics. However, MICs of CTM and CAZ were two- to four-fold higher than those of PCG, ABPC, CET and IPM, MICs of rokitamycin for the tested strains were higher than those of clarithromycin. MICs of CPFX and LVFX showed two-modal distributions. The first peak of distributions was observed between 0.06 to 0.5 microgram/ml and second one was between 4 to 16 micrograms/ml. These distributions suggested that MIC values of 4 to 16 micrograms/ml could result from the expression of a resistance mechanism. In addition, some of H. pylori strains were observed drug resistances between CP and AMK, new quinolones and AMK respectively. From the molecular epidemiological study, cryptic plasmids were detected from the 3 isolates among 24 strains tested.     

Antimicrobial activity of cefteram comparison with other oral antibiotics

Antimicrobacterial activities of cefteram (CFTM) against clinical isolates collected in 1988 were compared with those of new beta-lactams. 1. Antibacterial activities of CFTM against Streptococcus pneumoniae, Streptococcus pyogenes, Haemophilus influenzae, Branhamella catarrhalis isolated from acute respiratory tract infections were 8- to 16-fold higher than those of cefaclor (CCL). 2. Activities of cefixime (CFIX) were superior to those of CFTM against B. catarrhalis, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, but were inferior to CFTM against S. pneumoniae, S. pyogenes, Staphylococcus saprophyticus and Staphylococcus aureus. 3. Activities of cefuroxime were superior to those of CCL against each of the 4 tested bacterial species from acute respiratory tract infection and S. aureus by 4-fold, but were inferior to CFTM and CFIX against most of Gram-negative rods. 4. Sultamicillin (SBTPC) is considered to have an activity to inhibit beta-lactamase, but its MICs did not exceed the MICs of ampicillin by itself. SBTPC showed poor antibacterial activities against methicillin-resistant S. aureus (MRSA). Considering these observations, it is apparent that we are faced with a variety of factors in selecting antibiotics for best results.     

Susceptibility of Pseudomonas aeruginosa to aztreonam in comparison to other pseudomonas-active beta-lactam antibiotics and gentamicin

The in vitro activity of aztreonam, a synthetic monobactam, was evaluated against 245 strains of Pseudomonas aeruginosa, 130 of them being recent clinical isolates from patients and 115 from hospital environment. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and bactericidal kinetics were determined. The possibility of resistance development in vitro was studied. Gentamicin, cefsulodin, piperacillin and azlocillin were used as comparative agents with known antipseudomonal activity. At a concentration of 8 mg/l 83.3%, at 16 mg/l 92% of the tested strains were susceptible to aztreonam. Thus, the activity of aztreonam against Pseudomonas aeruginosa is equivalent to that of gentamicin and cefsulodin and better than that of piperacillin and azlocillin in terms of resistance. Bactericidal kinetics with fourfold MIC, which is equivalent to MBC, are nearly identical for aztreonam, piperacillin and cefsulodin. In vitro induced resistance additionally causes increased resistance against the other beta-lactam antibiotics.     

碳青霉烯类抗菌药物不合理使用干预对比研究

目的：通过对某三甲医院（以下简称某院）碳青霉烯类抗菌药物的处方进行初评和终评，发现不合理用药的问题并提出干预措施，提高该院该类抗菌药物的合理使用水平。方法：通过回顾性处方点评的方法，抽查2018年11月的113份病历作为干预前研究资料，抽取2019年2月份的82份病例作为干预后研究资料，依据相关规定和指南对使用碳青霉烯类抗菌药物的处方进行打分点评，再将分数结果反馈于各个科室，提出干预措施和跟踪管理。将干预前与干预后的数据进行统计对比分析。结果：干预前不合理率为37.2%，干预后不合理率为19.5%，干预前后差异有统计学意义（P<0.05），无用药指征，用法用量不适宜的干预后数量明显减少，但联合使用不规范、未进行病原学送检、未进行会诊及其它的不合理类型，在干预后数量未见明显改善，仍然存在不合理用药问题。结论：这种评分制的处方点评以及跟踪干预取得的效果较明显，值得推广，对提高碳青霉烯类抗菌药物的合理使用具有一定的借鉴意义。     

头孢硫脒与6种抗菌药物联用对金葡球菌的体外抗菌活性

目的:评价头孢硫脒分别与万古霉素、奈替米星、阿米卡星、环丙沙星、左氧氟沙星和加替沙星6种抗菌药物联合用药,对于临床分离的金葡球菌(SA)的体外联合抗菌效应.方法:经VITEK鉴定临床分离致病菌,采用棋盘法设计,微量肉汤稀释法测定6组抗菌药物对SA及耐甲氧西林金葡球菌(MRSA)的最低抑菌浓度,并计算部分抑菌指数(FIC指数). 结果:头孢硫脒与万古霉素、奈替米星、阿米卡星、环丙沙星、左氧氟沙星、加替沙星联合应用后,MIC50,MIC90明显降低,FIC指数<0.5占60%～90%,0.5～1占10%～30%,1～2占0～13.3%,>2为0.结论:头孢硫脒与6种抗菌药物联合应用后,对SA基本表现为协同和相加作用,说明联合用药的疗效要高于两药单独使用.     

In vitro antibacterial activity of imipenem against Pseudomonas and Staphylococcus species. Comparison with thirteen other antimicrobial agents

The in vitro antimicrobial activity of imipenem against recent clinical isolates of Pseudomonas spp. (94 strains) and penicillin-resistant Staphylococcus spp. (50 Staph. aureus and 50 coagulase-negative Staphylococcus) was assessed using the Mueller-Hinton agar dilution method. Results were compared with those simultaneously obtained for amikacin, netilmicin, tobramycin, norfloxacin, piperacillin, ceftazidime, ceftriaxone and azthreonam against Pseudomonas spp., and for rifampicin, clindamycin, netilmicin and cefoxitin, besides penicillin and methacillin, against Staphylococcus spp. About 50 and 90% of 84 Pseudomonas aeruginosa isolates were inhibited by concentrations of imipenem equal to or less than 2 and 8 mg/l respectively. The in vitro activity of imipenem was comparable to that of ceftazidime and norfloxacin, but superior to that of the aminoglycosides and all the other antibiotics tested, in terms of potency by weight. Among other Pseudomonas spp. only P. malthophilia (2 strains) proved resistant to imipenem. Rifampicin was the most active antibiotic by weight against Staph. aureus but imipenem was more active than clindamycin and, especially, netilmicin and cefoxitin. Imipenem was highly active also against coagulase-negative staphylococci, with some differences related to the high incidence of methicillin-resistant strains. MICs of imipenem in Mueller-Hinton broth correlated with those obtained in agar, unlike the aminoglycosides. There were no significant inoculum effects on MICs of imipenem and MBCs were within one twofold dilution of MICs in over 75% of assays.     

Adrenocortical suppression by synthetic corticosteroid drugs: a comparative study of prednisolone and betamethasone.

1 Single-dose studies were conducted to investigate the relative potency of prednisolone and betamethasone in suppressing adrenocortical function. 2 Betamethasone produced more profound suppression of plasma cortisol than an equivalent anti-inflammatory dose of prednisolone.     

Comparative in vitro activity of aztreonam and other antimicrobial agents against Salmonella species

The in vitro activity of aztreonam, the first monobactam antibiotic, was compared with that of 17 other antimicrobial agents against 79 strains of Salmonella species. The microorganisms were isolated from hospitalized patients, surface waters and seafoods during the decade 1975-1984. They included the following species: Salmonella typhi 63, Salmonella typhimurium 5, Salmonella wien 5, Salmonella heidelberg 2, Salmonella arizonae 2, Salmonella paratyphi B 1 and Salmonella enteritidis 1. The minimum inhibitory concentration (MIC) values of the antibiotics were determined using a serial dilution method in agar. A final inoculum size of 10(5) colony-forming units (CFU) X ml-1 of the tested microorganisms was used. Aztreonam exhibited a superior antimicrobial activity to that of the other antibiotics tested. Aztreonam inhibited 90% of the strains by 0.8 micrograms X ml-1 (MIC range was 0.05 to 1.56 micrograms X ml-1). There was no major difference between minimum bactericidal concentration and MIC values of aztreonam and the effect of inoculum size upon MIC values was observed at 10(7) CFU X ml-1.     

Antibacterial activity of moxalactam (LY-127935) compared with cefotaxime and other beta-lactam antibiotics against clinical isolates of enterobacteriacea and non-fermenters

The in vitro activity of moxalactam, a new semisynthetic 1-oxa-beta-lactam, was compared to those cefotaxime, cefuroxime, cephalothin, piperacillin and tobramycin against more than 500 clinical isolates of Enterobacteriaceae and non-fermenters. The geometric mean MIC against 450 Enterobacteriaceae in microgram/ml was 0.09 for moxalactam, 0.08 for cefotaxime, 5.3 for cefuroxime, 22.9 for cephalothin, 3.5 for piperacillin and 0.72 for tobramycin. The geometric mean MIC in microgram/ml against 60 P. aeruginosa strains was 12.7 for moxalactam, 22.9 for cefotaxime, 6.8 for piperacillin, 1.5 for tobramycin and 2.9 for cefsoludin. The minimum inhibitory and the bactericidal concentrations of moxalactam were almost the same in most species. The effect of the inoculum on the bactericidal concentration was slight, between 10(3) and 10(7) CFU/ml for the E. coli and the Klebsiella strains. In isolates of S. marcescens and P. aeruginosa the bactericidal concentrations increased by 4 to 5 log2 and in isolates of P. mirabilis the increased by 9 log2 with the largest inoculum.