Cephapirin: In Vitro Antibacterial Spectrum

Cephapirin, a new semisynthetic cephalosporin derivative, was found to have an antibacterial spectrum similar to that of cephalothin. Staphylococcus aureus was inhibited by cephapirin concentrations of 0.09 to 12.5 mug/ml. S. epidermidis, S. viridans, S. pyogenes, and Diplococcus pneumonia isolates were inhibited by less than 1 mug/ml. The Enterococcus required a concentration of 25 mug of antibiotic per ml for inhibition. Approximately 65% of Escherichia coli, and all Klebsiella, indole-negative Proteus, and Salmonella strains tested were inhibited by the drug. Serratia, Pseudomonas, indole-positive Proteus, and Erwinia strains were highly resistant. Inoculum size was not an important factor in determining the level of sensitivity of S. aureus to cephapirin. The antibiotic does not appear to be significantly bound to serum protein. In vitro development of resistance to the drug was demonstrated with two isolates of S. aureus.     

In Vitro Antimicrobial Activity and Human Pharmacology of Cephalexin, a New Orally Absorbed Cephalosporin C Antibiotic

Concentrations of cephalexin (an orally absorbed derivative of cephalosporin C) in serum and urine were determined in normal volunteers and patients. The in vitro antibacterial activity was also studied. All strains of group A β-hemolytic streptococci and Diplococcus pneumoniae were inhibited by 3.1 μg/ml. Of the Staphylococcus aureus strains, 88% were inhibited by 6.3 μg/ml, and 12.5 μg/ml was inhibitory for all S. aureus, 80% of Escherichia coli, 72% of Klebsiella-Aerobacter, and 56% of Proteus mirabilis strains. About 90 to 96% of E. coli, Klebsiella Aerobacter, and P. mirabilis strains were inhibited by 25 μg of cephalexin per ml. Pseudomonas and indole-positive Proteus strains proved to be quite resistant to cephalexin. Cephalexin was well absorbed after oral administration. A peak serum concentration of cephalexin of at least 5 μg/ml was achieved in each volunteer with 250 and 500-mg doses. A mean peak serum concentration of 7.7 μg/ml was achieved with 250-mg doses; 12.3μg/ml was achieved with 500-mg doses of antibiotic. Food did not interfere with absorption. Probenecid enhanced both the peak serum concentration and the duration of antibiotic activity in the serum. Over 90% of the administered dose was excreted in the urine within 6 hr. The mean peak serum concentration of cephalexin after an oral dose of 500 mg was adequate to inhibit all group A streptococci, D. pneumoniae, and S. aureus, 85% of E. coli, and about 40 to 75% of Klebsiella-Aerobacter and P. mirabilis strains. Levels of cephalexin in urine were adequate to inhibit over 90% of E. coli, and P. mirabilis and 80 to 96% of Klebsiella-Aerobacter strains.     

Semisynthetic Penicillin 6-[d(—)-α-Carboxy-3-Thienylacetamido] Penicillanic Acid Active Against Pseudomonas In Vitro

The activity of 6-[d(-)-alpha-carboxy-3-thienylacetamido] penicillanic acid, BRL2288, was determined against Pseudomonas aeruginosa and various gram-negative bacilli. The majority of Pseudomonas strains (89%) were inhibited by 100 mug of the antibiotic per ml. BRL2288 is twofold more active than carbenicillin against Pseudomonas at 100 mug/ml or less. Among Enterobacteriaceae tested, 87% Enterobacter and 87% of Proteus mirabilis strains were inhibited by 25 mug/ml or less. Indole-positive Proteus were inhibited by 10 mug/ml or less. Fifty-five per cent of ampicillin-resistant Escherichia coli were inhibited by 100 mug/ml. Klebsiella were uniformly resistant. BRL2288 is not hydrolyzed by most resistant Pseudomonas, but it is destroyed by the beta-lactamases of E. coli and P. mirabilis. The antibiotic shows synergy with gentamicin but not with penicillinase-resistant penicillins such as cloxacillin. Activity of BRL2288 against gram-positive organisms is two- to eightfold less than that of ampicillin or benzylpenicillin G.     

Effect of Inoculum Size on In Vitro Susceptibility Testing with Lincomycin

There is disagreement in the literature as to whether lincomycin is primarily a bacteriostatic or a bactericidal agent against gram-positive cocci and also regarding the levels of activity of this agent against susceptible microorganisms. These questions were examined in a study of the effect of inoculum size on the results of tube dilution susceptibility determinations with lincomycin against 49 clinical isolates of Staphylococcus aureus and 25 strains of streptococci and pneumococci. Lincomycin was both highly active and bactericidal when tested against 40 strains of S. aureus with inocula containing a maximum of 10(4) cells per ml [median minimal inhibitory concentration (MIC), 0.78 mug/ml; median minimal bactericidal concentration (MBC), 1.56 mug/ml]. With inocula of 10(5) cells per ml, lincomycin was primarily bacteriostatic (median MIC, 1.56 mug/ml; median MBC, 12.5 mug/ml). There were further decreases in inhibitory levels and significant losses of bactericidal activity when inocula containing more than 10(7) cells were tested (median MIC, 3.13 mug/ml; median MBC > 100 mug/ml). Similar measurements with streptococci and pneumococci revealed a lesser effect of inoculum size. The mean MBC value for alpha-hemolytic streptococci increased from 0.40 to 1.05 mug/ml with an increase in inocula from 10(4) to 10(6) cells per ml, but without a marked increase in MIC values. Similar results were obtained for beta-hemolytic streptococci and pneumococci.     

Cephalexin and Cephaloglycin Activity In Vitro and Absorption and Urinary Excretion of Single Oral Doses in Normal Young Adults

A large number of recently isolated bacterial pathogens were tested for susceptibility to cephalexin and cephaloglycin by the replica inoculating method. Strains of group A hemolytic streptococci, viridans (alpha and gamma) streptococci, pneumococci, gonococci, meningococci, and penicillin G-sensitive Staphylococcus aureus were all moderately to highly susceptible to both of these cephalosporin analogues, nearly all of the strains being two to eight (median four) times more susceptible to cephaloglycin than to cephalexin. The penicillin G-resistant, penicillinase-producing strains of S. aureus varied in their susceptibility; many were moderately resistant to both analogues, particularly to cephalexin. Strains of enterococci, Haemophilus influenzae, and most of the common gram-negative bacilli were moderately to highly resistant. Reducing the size of the inoculum had variable effects on inhibition by these drugs, depending on the species or strain. The activity of cephalexin was very little affected by pH of the medium within the clinical range or by incubation at 37 C in broth for up to 24 hr. In contrast, cephaloglycin in broth deteriorated rapidly at 37 C, and its activity was markedly reduced in alkaline medium. Both cephalexin and cephaloglycin were rapidly absorbed and excreted into the urine after single oral doses of 500 mg. Much higher levels were achieved and sustained with the former. Absorption of both analogues was delayed when taken with food, and the levels in the serum were significantly higher and better sustained when probenecid was also given. Very high concentrations of cephalexin were excreted into the urine during the first 4 hr, and the levels were still high in the 4- to 8-hr collection. The concentrations of cephaloglycin in the urine at these times were much lower. An average of 80 to 93% of the dose of cephalexin and 25 to 30% of the cephaloglycin were accounted for as active drug in the urine collected in 8 hr. Both analogues were well tolerated.     

Susceptibility of Salmonellae to Cephalosporins and to Nine Other Antimicrobial Agents

Three cephalosporin-related antibiotics and nine other antimicrobial agents were studied for in vitro effectiveness against 54 recently isolated strains of Salmonella. Minimal inhibitory concentrations determined by the plate dilution method demonstrated the following percentages of resistance: ampicillin, 6%; tetracycline, 13%; streptomycin, 52%; sulfadiazine, 94%; cephaloglycin, 96%; and lincomycin, 100%. No strains were resistant to cephalothin, cephaloridine, chloramphenicol, colistimethate, kanamycin, and polymyxin B. The commonest serotype studied, S. typhimurium, showed the greatest antibiotic resistance, with 21% resistant to ampicillin, 36% resistant to tetracycline, and 71% resistant to streptomycin. Cephalothin and cephaloridine were highly effective in vitro but inhibitory concentrations of 20 to 40 mug of cephaloglycin per ml were required for the majority of Salmonella strains.     

Microbiological exploitation of cardiac glycosides and alkaloids from Garcinia kola, Borreria ocymoides, Kola nitida and Citrus aurantifolia.

The four medicinal plants, Garcinia kola (roots), Borreria ocymoides (leaves), Kola nitida (bark) and Citrus aurantifolia (roots) were screened for phytochemical components. They were found to contain tannins, phlobatannins, polyphenols, hydroxymethyl anthraquinones, glucides, saponins, alkaloids, cardiac glycosides, flavanoids and reducing compounds. The aqueous and alcoholic extracts as well as alkaloids and cardiac glycosides of the medicinal plants were tested on various pathogenic bacteria. They were found to inhibit such organisms as Staphylococcus aureus, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, beta-haemolytic streptococci, Escherichia coli and Neisseria gonorrhoeae. The usefulness of the phytochemical bases of these plants as potential sources of pharmaceutical drug preparation is discussed.     

Group B streptococci inhibit the chemotactic activity of the fifth component of complement

Infection with group B streptococci (GBS) is associated with a poor acute inflammatory response in which neutrophils fail to localize at the site of invasion. In the present studies, we have examined the effects of group B streptococci on C-derived chemotactic activity in human serum. Fresh human serum was activated to form C5a and C5adesarg by incubation with zymosan. The activated serum was then incubated with group B organisms, centrifuged, and the supernatants tested for chemotactic activity for human polymorphonuclear leukocytes. Group B organisms caused a dose-dependent decrease in C-dependent chemotactic activity. The degree of inhibition was profound with 1 X 10(9) bacteria/ml (10% of control). Experiments indicated that significant chemotactic factor inactivation occurred within 2 min of exposure to GBS organisms, while maximal inhibition occurred after 30 min incubation. A number of different strains of GBS of types I, II, and III possessed inhibitory activity. In contrast, group D streptococci, Staphylococcus aureus, Escherichia coli and Klebsiella pneumoniae failed to inhibit the C-derived chemotactic activity in human serum. Group A streptococci that were M protein positive also inactivated C-dependent chemotactic activity in serum, as previously reported. The inhibitory activity of the GBS strains could be abolished by heat or trypsin treatment but not by neuraminidase, pronase, or pepsin. C5a levels in zymosan-activated serum as measured by RIA were not decreased after incubation with an inhibitory strain suggesting that absorption was not involved. SDS-PAGE analysis revealed that group B streptococci degrade the C5a molecule, increasing its electrophoretic mobility by removing a fragment with a m.w. of approximately 650 Da. Thus, one of the reasons for the poor inflammatory response at the site of GBS infection may reside in the ability of these pathogens to inactivate C-derived inflammatory mediators. The GBS C5a-ase activity probably serves as an additional virulence factor for these organisms contributing to the poor inflammatory response characteristic of group B streptococcal infection.     

Microbiological exploitation of cardiac glycosides and alkaloids from Garcinia kola, Borreria ocymoides, Kola nitida and Citrus aurantifolia

R.U.B. EBANA, B.E. MADUNAGU, E.D. EKPE AND I.N. OTUNG. 1991. The four medicinal plants, Garcinia kola (roots), Borreria ocymoides (leaves), Kola nitida (bark) and Citrus aurantifolia (roots) were screened for phytochemical components. They were found to contain tannins, phlobatannins, polyphenols, pydroxymethyl anthraquinones, glucides, saponins, alkaloids, cardiac glycosides, flavanoids and reducing compounds. The aqueous and alcoholic extracts as well as alkaloids and cardiac glycosides of the medicinal plants were tested on various pathogenic bacteria. They were found to inhibit such organisms as Staphylococcus aureus, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa , β-haemolytic streptococci, Escherichia coli and Neisseria gonorrhoeae. The usefulness of the phytochemical bases of these plants as potential sources of pharmaceutical drug preparation is discussed.     

Amoxycillin: A new Semi-synthetic Penicillin

Amoxycillin (α-amino-p-hydroxybenzylpenicillin) is a new semi-synthetic penicillin with a broad spectrum of antibacterial activity similar to that of ampicillin. Penicillin-sensitive strains of staphylococci, streptococci, and pneumococci were sensitive to concentrations of 0·1 μg or less of amoxycillin/ml. Strains of Haemophilus influenzae were inhibited by a level of 0·5 μg/ml, and most strains of Escherichia coli, Proteus mirabilis, Shigella sonnei, Salmonella species, and Streptococcus faecalis were sensitive to a concentration of 5 μg or less of amoxycillin/ml. Penicillinase-producing strains of Staphylococcus aureus and strains of Pseudomonas aeruginosa, indole-positive Proteus, Klebsiella, and Enterobacter were insensitive to amoxycillin. The new penicillin was bactericidal in activity, as with other penicillins, and its antibacterial activity was not reduced in the presence of serum. After oral administration to volunteer subjects amoxycillin produced serum concentrations twice as high as those obtained with similar doses of ampicillin, and the penicillin was recovered unchanged in high concentrations in the urine. The absorption of amoxycillin was not greatly influenced by food, and administration of probenecid resulted in increased and more prolonged concentrations of amoxycillin in serum.     

Effect of Thymine Limitation on Chromosomal Deoxyribonucleic Acid Synthesis in Proteus mirabilis

The effects of thymine limitation on the rates of growth, deoxyribonucleic acid (DNA) synthesis, and increase in viable cell number for a thymine auxotroph of Proteus mirabilis were investigated. At thymine concentrations of 1.0 mug/ml and below, these rates were markedly decreased. After a reduction in thymine concentration from 10 mug/ml to 0.2 mug/ml, mass synthesis continued at the preshift rate for several hours. In contrast, the rate of DNA synthesis immediately decreased, resulting in a decrease in the DNA to mass ratio to about one-half of its normal level. Viable counts remained constant for several hours after the reduction in thymine concentration, and enlarged cells and multicellular "snakes" were formed. The rate of DNA synthesis was reduced at thymine concentrations below approximately 1.7 mug/ml. The addition of thymine to cultures which had been completely starved for thymine increased the rate of DNA synthesis to at least twice its normal value; this suggests that extra rounds of chromosome replication can be induced in P. mirabilis as previously observed in Escherichia coli.     

In Vivo and In Vitro Action of Norethindrone on Staphylococci

Norethindrone has been examined in vitro for antibacterial activity against 10 microorganisms. Turbidimetric techniques were used to assay the antibacterial activity of norethindrone. The organisms tested included Staphylococcus aureus, S. epidermidis, Micrococcus conglomeratus, Listeria monocytogenes, Streptococcus faecalis, Salmonella typhosa, Shigella flexnerii, Klebsiella pneumoniae, Escherichia coli, and Proteus vulgaris. Bacteriostatic action was shown only against the gram-positive microorganisms when they were grown anaerobically in Tryptic Soy Broth containing 10 to 50 mug of norethindrone per ml. The bacteriostatic action of norethindrone was exerted primarily during the first 8 hr of incubation and it was reduced by the presence of oxygen. Mestranol at a concentration of 1 to 10 mug/ml failed to exert any significant action on S. aureus. However, incorporation of 5 mug of mestranol per ml in the culture medium enhanced the bacteriostatic action of norethindrone on staphylococci. Enhancement of the bacteriostatic action of norethindrone could not be obtained by the addition of a concentration of 5 mug/ml of testosterone, 17alpha-estradiol, and 17beta-estradiol. Progesterone and 4-pregnen-20beta-ol-3-one under similar conditions showed an additive bacteriostatic effect when they were incorporated into the culture medium containing norethindrone. In vivo studies indicated that female, adult New Zealand rabbits, injected subcutaneously with two injections of 10 to 20 mug of norethindrone, 24 hr apart, and challenged intradermally with S. aureus 4 hr after the second injection, had fewer lesions with smaller areas of swelling and erythema as compared to control, nontreated rabbits. The protective effect of norethindrone on the development of staphylococcal lesion seemed related to hormone concentration. Thus, it was demonstrated with doses of 20, 15, and 10 mug, but not with doses of 1 and 5 mug. When the lesions were excised 48 to 92 hr after infection and when viable cell counts were made, rabbits treated with norethindrone showed significantly lower staphylococcal counts than the control rabbits. During the 1st day after infection with S. aureus, leukocytic counts of the norethindrone-treated rabbits remained normal, whereas control animals showed elevated leukocytic counts.     

糖尿病患者足部溃疡感染的病原菌分布及药敏性分析

目的:研究糖尿病患者足部溃疡感染的病原菌分布及药敏性。方法:选取2016年2月至2017年2月我院收治的糖尿病足患者102例作为研究对象,采用全自动细菌鉴定仪和Kirby-Baure(K-B)法分别检测所有患者足部溃疡分泌物中病原菌分布和药敏性。结果:96例成功分离出菌株的糖尿病患者足部溃疡分泌物中共分离出107株菌株,其中革兰阴性菌61株(57.01%)、革兰阳性菌43株(40.19%)和真菌3株(2.80%),占总菌株百分比前三位的病原菌分别为金黄色葡萄球菌22株(20.56%)、奇异变形杆菌14株(13.08%)和肺炎克雷伯菌10株(9.35%);前三位革兰阴性菌(奇异变形杆菌、肺炎克雷伯菌和大肠埃希菌)对亚胺培南、美罗培南、头孢哌酮及阿米卡星的敏感性较高(高于90.00%);金黄色葡萄球菌和表皮葡萄球菌对万古霉素、利奈唑胺及利福平敏感性较高(高于95.00%);粪肠球菌对红霉素、氨苄西林、万古霉素及利奈唑胺敏感性较高(高于90.00%)。结论:糖尿病患者足部溃疡感染的病原菌以金黄色葡萄球菌和奇异变形杆菌为主,耐药情况严峻,临床诊疗过程中应根据药敏结果规范使用抗菌药物。     

Novel shuttle vectors for improved streptokinase expression in streptococci and bacterial L-forms

Novel shuttle vectors of small size and increased copy number capable of replication in Escherichia coli, L-forms of Proteus mirabilis, and streptococci were constructed from a streptococcal erythromycin-resistant plasmid and an Escherichia coli phasmid. The streptokinase gene, skc, was inserted into one of them, and skc expression was studied in Streptococcus sanguis, Streptococcus lactis, and in an L-form strain (LVI) of Proteus mirabilis. The new streptokinase shuttle plasmid, pMLS10 (7.3 kb), specified higher Skc yields in all hosts when compared to pSM752 constructed previously. In particular Proteus mirabilis LVI(pMLS10) proved to be the most productive host, exhibiting complete secretion of the active protein at yields as high as 24000 unit per ml.     

In Vitro Studies of Semisynthetic α- (Substituted-Ureido) Penicillins

The activity of three alpha-(substituted-ureido) penicillins was evaluated in vitro against 599 clinical isolates of gram-negative bacilli, by use of the broth-dilution technique. At a concentration of 12.5 mug or less/ml, BL-P1597 inhibited 90% of isolates of Pseudomonas sp., 56% of Enterobacter sp., 67% of indole-positive Proteus spp., 72% of Escherichia coli, and 85% of Proteus mirabilis. BL-P1654 had similar activity, whereas BL-P1532 was much less active. At a concentration of 25 mug or less/ml, BL-P1597 also inhibited nearly 60% of isolates of Klebsiella sp. and nearly 40% of Serratia sp. BL-P1597 and BL-P1654 were as active as ampicillin and carbenicillin against E. coli and P. mirabilis. They were less active than carbenicillin against indole-positive Proteus spp. Both drugs were substantially more active than carbenicillin against Pseudomonas sp. A strain of Pseudomonas sp. which developed resistance to carbenicillin also developed resistance to the alpha-(substituted-ureido) penicillins simultaneously.     

Nosopharyngeal microflora in ambulatory treated children and adults with upper respiratory tract infections

Upper respiratory tract consists resident and transient bacterial microflora, which in appropriate condition can cause infection. Bacteriological study was performed among 201 patients with upper respiratory tract infections treated in ambulatory. From nasal and pharyngeal swabs Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, and Streptococci group A, B, C, G were isolated. Antibiotic susceptibility testing of isolated strains was performed using CLSI criteria. All isolated strains of streptococci were susceptible to penicillin; some of them demonstrated resistance to macrolides and lincosamides. Few isolated strains of H. influenzae demonstrated resistance to penicillin and cotrimoxazole. Azitromycin resistant strains were not detected. All isolated strains of M. catarrhalis were beta-lactamase positive and demonstrated resistance to penicillin. Strains of methicillin sensitive S. aureus (MSSA) were isolated most frequently from pharyngeal swabs (35.4%) and S. pneumoniae (33.3)--from nasal swabs.     

The establishment of resistance phenotypes for bacteria isolated from outpatients in urine cultures

From 1911 outpatients, who addressed a Timi?oara private clinical laboratory, from January to December 2005, we collected 1,889 urine cultures, 431 being positive. Bacteria identification was generally done using morphological, cultural, biochemical characters and pathogenicity tests. Sensitivity testing to antimicrobial medical drugs was done by using the classical diffusion Kirby-Bauer method and the automatic analyzer Osiris, also. The main bacteria involved in the etiology of these infections were represented by Enterobacteriaceae, head of the list being Escherichia coli (81.21%), followed by Klebsiella pneumoniae (8.35%) and Proteus mirabilis (3.02%). We also isolated Gram positive cocci (in a much smaller proportion), mainly represented by Enterococcus faecalis (1.16%), Staphylococcus aureus (0.93%), Streptococcus agalactiae, and also Gram negative non-fermentative bacilli, such as Pseudomonas aeruginosa (0.93%) or Acinetobacter baumanii (0.23%). As soon as we performed the sensitivity tests, we divided them in resistance phenotypes: Most of the Enterobacteriaceae were integrated in the wild phenotype, followed by the penicillinase producing phenotype. An E. coli strain (0.29%) and 3 Klebsiella pneumoniae strains (8.33%) were integrated in the large spectrum, multidrug resistant, beta-lactamase producing phenotype, also associated with resistance to fluoroquinolones and aminoglycosides; Non-fermentative bacilli did not present special resistance problems, the four Pseudomonas aeruginosa strains were integrated in the wild phenotype (secreting induced chromosomal cephalosporinase). As for Staphylococcus aureus it was identified a strain having fluoroquinolone resistance, two strains secreting penicillinase and having a K (Nm) phenotype and a strain secreting penicillinase only. Antibiotic resistance represents a major concern for patients, physicians, healthcare managers, and policymakers. The use of antibiotics is closely linked with the development of acquired antibiotic resistance.     

Bacterial effect of hydrogen peroxide on urinary tract pathogens.

Bacterial contamination of urinary drainage bags is a frequent source of bladder bacteriuria in patients with indwelling catheters. Previous work demonstrated that the addition of 30 ml of 3% H2O2 prevented bacterial contamination of urinary drainage bags for up to 8 h in patients with urinary infections (greater than 10(5) colony-forming units per ml). Survival curves of a variety of organisms in filter-sterilized urine with various concentrations of H2O2 (0.6 to 0.01%) were constructed. Organisms with high cellular catalase activity (Staphylococcus aureus, Serratia marcescens, and Proteus mirabilis) required 30 to 60 min of exposure to 0.6% H2O2 for a reduction of 10(8) to less than 1 colony-forming unit per ml, whereas Escherichia coli, Streptococcus sp., and Pseudomonas sp. required only 15 min of exposure. The efficacy of H2O2 in urine was maintained despite exposure to room temperature for 5 days and reinoculation with bacterial suspensions. H2O2 is inexpensive and relatively nontoxic, and these data suggest that periodic instillation of H2O2 into urinary drainage bags may eliminate a source of bladder bacteriuria and environmental contamination.     

Antiviral and antimicrobial assessment of some selected flavonoids

In the current study, the results of antibacterial, antifungal, and antiviral activity tests of four flavonoid derivatives, scandenone (1), tiliroside (2), quercetin-3,7-O-alpha-L-dirhamnoside (3), and kaempferol-3,7-O-alpha-L-dirhamnoside (4), are presented. Antibacterial and antifungal activities of these compounds were tested against Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, Acinetobacter baumannii, Staphylococcus aureus, Bacillus subtilis, and Enterococcus faecalis, as well as the fungus Candida albicans by a micro-dilution method. On the other hand, both DNA virus Herpes simplex (HSV) and RNA virus Parainfluenza-3 (PI-3) were employed for antiviral assessment of the compounds using Madin-Darby bovine kidney and Vero cell lines. According to our data, all of the compounds tested were found to be quite active against S. aureus and E. faecalis with MIC values of 0.5 microg/ml, followed by E. coli (2 microg/ml), K. pneumoniae (4 microg/ml), A. baumannii (8 micro/g/ml), and B. subtilis (8 microg/ml), while they inhibited C. albicans at 1 microg/ml as potent as ketoconazole. However, only compound 3 displayed an antiviral effect towards PI-3 in the range of 8-32 microg/ml of inhibitory concentration for cytopathogenic effect (CPE).     

Effect of Different Media on In Vitro Studies of Antibiotic Combinations

In an effort to determine the adequacy of a standard broth medium in the evaluation of antibiotic combinations, 20 strains of various bacterial species were studied simultaneously in Mueller-Hinton broth and in freshly drawn human serum from apparently healthy volunteers. Studies of growth dynamics by use of the usual plate dilution technique for quantitating colony-forming units were performed with strains of Staphylococcus aureus (methicillin-resistant and methicillin-susceptible), Streptococcus faecalis, Escherichia coli, Aerobacter, Klebsiella, and Proteus mirabilis. A variety of different antibiotics were investigated. With 19 of the 20 strains, interpretations of synergism or antagonism were the same in both media. Therefore, despite minor variations when the same strain was studied in both serum and broth, it is concluded that Mueller-Hinton broth is an adequate medium for use in studies of chemotherapeutic combinations in vitro. A simplified method for studying bactericidal activity is described, which is deemed practical for clinical microbiology laboratories and which led to the same conclusions regarding the combinations as were obtained by the more arduous plate dilution test.