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At least 721 records · Page 40Linked to original sources
PubMed1984

Mode of action and in-vitro activity of vancomycin.

Vancomycin is a unique glycopeptide structurally unrelated to any currently available antibiotic. It also has a unique mode of action inhibiting the second stage of cell wall synthesis of susceptible bacteria. There is also evidence that vancomycin alters the permeability of the cell membrane and selectively inhibits ribonucleic acid synthesis. Induction of bacterial L-phase variants from susceptible organisms with vancomycin is extremely difficult, and such variants are unstable. Stable L-phase variants induced by other agents are susceptible to vancomycin. Vancomycin is active against a large number of species of Gram-positive bacteria, such as Staphylococcus aureus (including methicillin-resistant strains), Staph. epidermidis (including multiple-resistant strains), Streptococcus pneumoniae (including multiple-resistant strains), Str. pyogenes, Str. agalactiae, Str. bovis, Str. mutans, viridans streptococci, enterococci, Clostridium species, diphtheroids, Listeria monocytogenes, Actinomyces species and Lactobacillus species. There has been no increase in resistance to vancomycin during the past three decades. Enhancement of antimicrobial activity has been demonstrated with the combination of vancomycin and an aminoglycoside against Staph. aureus, Str. bovis, enterococci and viridans streptococci. The combination of vancomycin and rifampicin are antagonistic to most strains of Staph. aureus, though indifference and occasionally synergism have been shown, but is synergistic against strains of Staph. epidermidis. It shows indifference against enterococci. Vancomycin and fusidic acid are indifferent against Staph. aureus.

Actinomycetales↗
PubMed1986

Mupirocin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use.

Mupirocin (pseudomonic acid A) is a novel topical antibacterial agent which inhibits bacterial protein and RNA synthesis. It has excellent in vitro activity against staphylococci and most streptococci, but has less activity against other Gram-positive and most Gram-negative bacteria. Its rapid systemic metabolism means it will only be used topically which, combined with its novel chemical structure, should make cross-resistance less likely to occur than with other currently available topical antibacterial agents. Mupirocin 2% ointment administered 2 or 3 times daily has shown excellent efficacy in both primary and secondary superficial skin infections, usually with at least 80% of patients being clinically cured or markedly improved, and over 90% eradication of the bacterial pathogen involved. Efficacy in impetigo and, to a somewhat lesser extent, infected wounds has been particularly convincingly demonstrated, while in other secondary skin infections the clinical response seen with mupirocin was often similar to the high success rate of vehicle alone. Limited evidence suggests that mupirocin may be as effective as chlortetracycline, fusidic acid, neomycin and other antibacterial agents, but more controlled, comparative studies are needed. The evidence of efficacy against nasal carriage of Staphylococcus aureus, including methicillin-resistant forms, is encouraging and currently work is being undertaken to improve the acceptability of the vehicle for this use. Side effects are limited to local reactions (in less than 3% of patients) and are no more frequent than observed with the vehicle alone. Thus, mupirocin appears to be a useful addition to the agents available for the treatment of superficial primary skin infections, such as impetigo, although its precise place in therapy remains to be established.

Administration, Cutaneous↗
PubMed1993

Staphylococcus aureus meningitis. A review of 104 nationwide, consecutive cases.

METHODS: Based on a nationwide registration, the clinical and bacteriologic data from 61 postoperative and 43 hematogenous cases of Staphylococcus aureus meningitis in Denmark from 1986 through 1989 were reviewed. RESULTS: Postoperative meningitis was a foreign body infection in 89% of the cases and had a lower mortality (18% [11/61]) compared with hematogenous meningitis (56% [24/43]). Hematogenous S aureus meningitis seems to be part of an overwhelming, disseminated infection as indicated by the following: 81% of the patients had bacteremia, 21% had endocarditis, and 12% had osteomyelitis. Most patients were older, often with underlying diseases, community-acquired infections, and a clinical picture of severe meningitis. The major findings were mental status changes and a high rate (34%) of focal neurological changes. The initial leukocyte count in the cerebrospinal fluid sample was low, and the bacteria were seen in Gram's stain smears in 40% of cases only. The prognosis was related to the age of the patients and the initial antibiotic treatment. Patients treated with penicillinase-stable penicillins in combination with fusidic acid may have a better prognosis. Three (12%) of 25 surviving patients had severe sequelae. CONCLUSIONS: Hematogenous S aureus meningitis is a severe disease with a high mortality related to age, presence of shock, and infection with strains of phage type 95.

Adolescent↗
PubMed1987

Transcriptional termination at a fully rho-independent site in Escherichia coli is prevented by uninterrupted translation of the nascent RNA.

We have examined the possibility that translation reading through a fully rho-independent transcriptional terminator in Escherichia coli might prevent termination, as already established for rho-dependent terminators. Plasmids were constructed with and without interposition of the rho-independent coliphage T7 'early' terminator between a promoter and galK. Our constructions ensured either that there was no upstream translation, or that translation (initiated at the galE ribosome binding site) stopped upstream of, or at the normal position (the T7 gene 1.3 stop codon) with respect to, the transcriptional terminator; or else downstream of both this stop codon and the terminator. Our galactokinase enzyme and mRNA measurements on strains harbouring these plasmids indicate that 'readthrough translation' eliminates transcriptional termination at the T7 site. This effect is suppressed if the rate of ribosome movement is reduced with fusidic acid.

Base Sequence↗
PubMed2005

Occurrence of heavy metal-resistance in microflora from serpentine soil of Andaman.

Serpentine soils collected from Saddle Hills, Chidyatapu and Rutland of Andaman Islands, India were analyzed for physico-chemical and microbiological characteristics and compared with those from adjacent non-serpentine localities. The serpentine soils contained high levels of nickel (1740.0-8033.4 mg/kg dry soil), cobalt (93.2-533.4 mg/kg dry soil) and chromium (302.9-4437.0 mg/kg dry soil), in addition to 62-152 g of iron and 37-60 g of magnesium per kg dry soil. Characteristically the serpentine soils showed low microbial density (6.2-11.3 x 10(6) colony forming unit/g soil) and activity (1.7-3.5 microg fluorescein/g dry soil/h) than non-serpentine outcrops. Serpentine microbial population was dominated by bacteria which represented 5.12 to 9.5 x 10(6) cfu/g of soil, while the fungal population ranged from 0.17 to 3.21 x 10(6) cfu/g of soil. A total of 342 (200 from serpentine and 142 from non-serpentine soils) isolates were compared for Ni, Co and Cr resistance. Serpentine microflora was in general, highly resistant than non-serpentine ones and showed a metal-resistance profile of Cr > Ni > Co. Amongst the serpentine isolates, 8 and 11 bacteria tolerated > 12.0 mM Ni and > 16.0 mM Cr respectively, while 6 fungal isolates showed a minimum inhibitory concentration (MIC) value > 8.0 mM Co. These 25 serpentine strains also showed co-resistance to Cu, Zn and Mn but were sensitive to Hg and Cd. The selected bacterial isolates were resistant to ampicillin, penicillin G and polymyxin B, whereas fungal strains showed resistance to amphotericin B, nystatin and fusidic acid.

Anti-Bacterial Agents↗
PubMed1989

Improvement of systemic absorption of insulin through eyes with absorption enhancers.

A painless, simple, and practical method has been developed for systemic delivery of peptide drugs through eyes. In order to increase the amount of peptides absorbed into systemic circulation, effects of enhancers on insulin absorption into systemic circulation and reduction of blood glucose concentration have been studied. Saponin showed the highest potency to enhance insulin absorption, while Tween 20 was the least effective. The efficacy order of seven compounds studied can be arranged as follows: saponin greater than fusidic acid greater than BL-9 = EDTA greater than glycocholate = decamethonium greater than Tween 20. Since 1% of saponin reached the maximum effect to enhance insulin absorption and decrease blood glucose concentration, not more than 1% of saponin should be used for enhancing peptide absorption through eyes.

Absorption↗
PubMed2000

Conformational changes in the ribosome induced by translational miscoding agents.

Ribosomes are dynamic complexes responsible for translating the genetic information encoded in mRNAs to proteins. The accuracy of this process is vital to the survival of an organism, and is often compromised by translational miscoding agents. Aminoglycosides are a group of miscoding agents that bind to the ribosome and reduce the fidelity of translation. Previous studies have shown that aminoglycosides alter the higher order structure of the ribosome. Here, we used a toeprinting assay to how that streptomycin, neomycin, kanamycin, gentamycin, and hygromycin B trigger conformational changes within Escherichia coli ribosome. Miscoding agents viomycin and 30% ethanol also cause similar structural changes within the ribosome. In contrast, antibiotics that do not cause miscoding, such as tetracycline, chloramphenicol, erythromycin, fusidic acid and spectinomycin, do not induce the conformational changes triggered by miscoding agents. Furthermore, ribosomes isolated from strains that are either streptomycin resistant or dependent for growth do not show these conformational changes in the presence of streptomycin. These results correlate structural changes in the ribosome induced by miscoding agents in vitro with their in vivo phenotype.

Anti-Bacterial Agents↗
PubMed2000

Treatment of Clostridium difficile-associated diarrhea and colitis.

Treatment of C. difficile diarrhea with metronidazole or vancomycin is highly effective at relieving symptoms. The high rate of diarrhea recurrence is concerning, but fortunately most patients respond to a second course of treatment. The problem of vancomycin resistance in hospital organisms has markedly reduced usage of this agent as a first-line treatment for C. difficile diarrhea, leaving metronidazole as the mainstay of treatment in the United States where teicoplanin and fusidic acid are not marketed. It is likely that any new antimicrobial agent used to treat C. difficile will be similarly plagued by a high rate of recurrence, presumably incurred as a result of disruption of normal bowel flora. There is a need for improved treatment and prevention of this increasingly frequent and debilitating nosocomial infection. Treatments that utilize passive antibodies, immunization, nontoxigenic C. difficile, or other forms of biotherapy may hold the key to improved treatment and prevention of C. difficile disease in the future. In the meantime, it behooves all practitioners to use antimicrobials judiciously in order to prevent as many cases of C. difficile diarrhea as possible.

Abdomen, Acute↗
PubMed1980

Translational accuracy enhanced in vitro by (p)ppGpp.

The effect of (p)ppGpp on the accuracy of translation in vitro was studied with a system that has a missense error frequency similar to that of living bacteria. When poly (U) is translated, limitation of the system in Phe increases the Leu missense error frequency. The introduction of (p)ppGpp to the Phe-limited mixtures reduces significantly the missense errors as well as reduces the rate of translation. The introduction of (p)ppGpp to a full system has no effect on the accuracy of translation but does reduce its rate. The effects of (p)ppGpp on rate and accuracy of translation can be simulated in part by other inhibitors of translation such as GDPCP, fusidic acid and tetracycline. Furthermore, the presence of ppGpp or GDPCP in a Phe-limited system leads to an accumulation of Phe-tRNA, while a Phe-limited system that contains only GTP has negligibly small concentrations of Phe-tRNA. We conclude that one way in which (p)ppGpp improves the accuracy of translation is by permitting the system to maintain a favorable Phe-tRNA/Leu-tRNA ratio.

Cell-Free System↗
PubMed1978

Cloning and characterization of EcoRI and HindIII restriction endonuclease-generated fragments of antibiotic resistance plasmids R6-5 and R6.

DNA fragments generated by the EcoRI of HindIII endonucleases from the low copy number antibiotic resistance plasmids R6 and R6-5 were separately cloned using the high copy number ColE1 or pML21 plasmid vectors and the insertional inactivation procedure. The hybrid plasmids that were obtained were used to determine the location of the EcoRI and HindIII cleavage sites on the parent plasmid genomes by means of electron microscope heteroduplex analysis and agarose gel electrophoresis. Ultracentrifugation of the cloned fragments in caesium chloride gradients localized the high buoyant density regions of R6-5 to fragments that carry the genes for resistance to streptomycin-spectinomycin, sulfonamide, and mercury and a low buoyant density region to fragments that carry the tetracycline resistance determinant. Functional analysis of hybrid plasmids localized a number of plasmid properties such as resistances to antibiotics and mercury and several replication functions to specific regions of the R6-5 genome. Precise localisation of the genes for resistance to chloramphenicol, kanamycin, fusidic acid and tetracycline was possible due to the presence of identified restriction endonuclease cleavage sites within these determinants. Only one region competent for autonomous replication was identified on the R6-5 plasmid genome and this was localized to EcoRI fragment 2 and HindIII fragment 1. However, two additional regions of replication activity designated RepB and RepC, themselves incapable of autonomous replication but capable supporting replication of a linked ColE1 plasmid in polA- bacteria, were also identified.

Bacteriocin Plasmids↗
PubMed1979

Plasmid replication functions. II. Cloning analysis of the repA replication region of antibiotic resistance plasmid R6-5.

R6-5 is a low copy number, conjugative, FII incompatibility group plasmid that has a molecular length of 102 kb and that specifies resistance against several antibiotics (chloramphenicol, fusidic acid, kanamycin, streptomycin and sulphonamide) and mercury salts. By means of in vitro cloning procedures, mini plasmids have been generated that contain a DNA segment from the essential region of R6-5 that is only 2.6 kb in length. This DNA segment, which consists of two PstI fragments that are adjacent in the parent plasmid, carries all genes and sequences required for the regulated replication and incompatibility properties of R6-5, including its origin of replication, OriV, an essential function that has been designated RepA, and the copy control function, Cop. Three different polypeptides, having monomer molecular weights of 23,000, 10,000 and 9,500 daltons, are synthesized in detectable quantities by minicells carrying pBR322 hybrid plasmids that contain DNA segments from the R6-5 essential region. A spontaneous deletion derivative of a pBR322 hybrid plasmid that carries the R6-5 origin of replication was isolated. Heteroduplex analysis of this derivative plasmid indicates that the deleted DNA segment carries the R6-5 replication origin and that its termini consist of short inverted repeat sequences.

DNA Polymerase I↗
PubMed1976

In vitro transcription of the tryptophan operon in isolated bacterial nucleoids.

In vitro transcription of the trp operon in isolated nucleoids from Escherichia coli was studied. RNA synthesis in this system occurred primarily as a continuation of transcription which had been initiated in vivo; little or no initiation of new RNA chains was observed. Transcription of the trp operon in nucleoids by endogenous RNA polymerase procedded efficiently and ceases sequentially in the order of the gene sequence within the operon. Under these conditions, no appreciable exonuccleolytic digestion of nascent 3H-RNA was found, though some endonucleolytic cleavage was generally seen. Little or no incorporation of 14C-leucine into polypeptides was observed, inspite of tha fact that considerable number of ribosomes and nascent RNA chains were found attached to the isolated nucleoids. The synthesis of trp mRNA continued in the presence of chloramphenicol or fusidic acid, or under conditions where the rebosomal translocation factor G was inactivated. From these and other kinetic studies of trp mRNA synthesis in nucleoids obtained from nonsense strong polar mutants of the trp operon, it was shown that transcription in nucleoids was not connected functionally with transloational processes and thus unable to exhibit polarity effected by a nonsense mutation or by general translational blockage. In studies employing nucleoids from nonsense strong polar mutants of the trp operon, it was demonstrated that RNA polymerase are scantily distributed over the region downstream from the nonsense mutation site of the operon, thereby supporting a notion that in vivo transcription is eventually terminated near the nonsense mutation.

DNA, Bacterial↗
PubMed1976

A form of elongation factor G insensitive to N-ethyl-maleimide.

Treatment of elongation factor G (EF-G) with the thiol reagent N-ethylmaleimide only partially inhibits (10 to 70%) the activity of the factor in (a) guanosine nucleotide-EF-G-ribosome complex formation, (b) uncoupled ribosome-dependent GTP hydrolysis, and (c) polypeptide synthesis. Moreover, a similar treatment of the factor with N-[3H]ethylmaleimide does not lead to 3H-label being associated with a GDP-EF-G-ribosome-fusidic acid complex. Thus, the results indicate the presence in EF-G preparations of a form of the factor that does not react with N-ethylmaleimide.

Binding Sites↗
PubMed1996

Increased resistance among Staphylococcus epidermidis isolates in a large teaching hospital over a 12-year period.

The prevalence of drug resistance among clinically significant blood isolates of Staphylococcus epidermidis (n = 464) and consumption of antibiotics at a tertiary care teaching hospital (Meilahti Hospital, Helsinki) were analysed for the period 1983-1994. Resistance to methicillin increased from 28 to 77%. Simultaneously, usage of third-generation cephalosporins increased nearly sevenfold (from 8.6 kg/ to 56.4 kg/year). A significant correlation was found between percentages of methicillin resistance and usage of penicillinase-stable beta-lactam agents, including cloxacillin, imipenem, and first-, second-, and third-generation cephalosporins (r = 0.737, p < 0.0062). The increase in ciprofloxacin resistance occurred soon after the introduction of ciprofloxacin. Moreover, there was a remarkable increase in resistance to fusidic acid (from 10 to 40%) and rifampin (from 0 to 23%) despite the low usage of these agents. Overall, the rate of multiply resistant isolates roughly tripled (from 20 to 71%) and, by 1994, the frequency of isolates susceptible to vancomycin only was as high as 11%, which remarkably limits options for therapy.

Adult↗
PubMedDate not supplied

Septic osteomyelitis and polyarthritis with ureaplasma in hypogammaglobulinemia.

We describe a hypogammaglobulinemic woman with a one-year history of destructive septic osteomyelitis and polyarthritis with positive cultures for Ureaplasma urealyticum from joint exudate and blood. The clinical course was complicated by subcutaneous abscesses from which both U. urealyticum and Mycoplasma hominis were grown. Multiple routine cultures had been negative, except for sporadic findings of Staphylococcus epidermidis before specific cultures for mycoplasmas were performed. Therapy with beta-lactam antibiotics, clindamycin, rifampicin, fusidic acid and aminoglycosides had been given without obvious clinical effect. Intravenous doxycycline treatment instituted after microbiological diagnosis had a dramatic effect on the clinical course. The clinical suspicion of mycoplasma and ureaplasma as etiologic agents of orthopaedic infections in hypogammaglobulinemic patients is mandatory in order to perform appropriate cultures.

Adult↗
PubMed1986

The activity of ofloxacin against methicillin-resistant Staphylococcus aureus.

The return of multiresistant Staphylococcus aureus strains and the appearance of methicillin-resistant strains resistant as well to rifampin and fusidic acid increase the need for new agents to treat infections caused by such strains. Ofloxacin susceptibility of 109 selected methicillin-resistant staphylococci (with MIC90 of 1,000 mg/l for methicillin, 1.3% being resistant to gentamicin with MICs ranging from 25 to 100 mg/l, chloramphenicol MICs ranging from 25 to 100 mg/l and resistant to beta-lactam-antibiotics and clindamycin), was determined by an agar dilution method. MICs of ofloxacin for methicillin-resistant staphylococci ranged from 0.09 to 0.78 mg/l, with an MIC90 of 0.39 mg/l. The in vitro results suggest a possible clinical role for ofloxacin in infections caused by methicillin-resistant staphylococci. However, further investigations are needed.

Anti-Bacterial Agents↗