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PubMed1983

Spontaneous, elongation factor G independent translocation of Escherichia coli ribosomes.

In a classical translocation experiment, deacylated RNA is bound to the ribosomal peptidyl-tRNA site (P site) and N-acetyl-phenylalanyl-tRNA (AcPhe-tRNA) to the aminoacyl-tRNA site (A site); upon addition of elongation factor (EF-G) and GTP, AcPhe-tRNA is translocated from the A to the P site. Here, we demonstrate a model reaction for a spontaneous, EF-G independent translocation. If AcPhe-tRNA is bound to the P site and Phe-tRNA to the A site at 15 mM Mg2+, then at 37 degrees C up to 60% of the AcPhe2-tRNA formed is found at the P site without the addition of EF-G. We demonstrate the following: 1) the spontaneous translocation is not merely illusory as a result of Phe-tRNA binding directly to the P site; 2) it is not mimicked by release of AcPhe2-tRNA from an A site and rebinding to a P site of another ribosome; 3) it is not caused by an EF-G contaminant present in the 70 S preparation, since without EF-G the spontaneous translocation works equally well in the presence of guanyl-5'-yl imidodiphosphate or fusidic acid; 4) AcPhe2-tRNA evidently has a higher affinity for the P site than AcPhe-tRNA, thus promoting the spontaneous translocation; and 5) peptide-bond formation favors the subsequent translocation. Addition of EF-G increases the initial rate by a factor of 13. Furthermore, at 15 mM Mg2+, 37 degrees C and in the presence of EF-G and GTP, Phe-tRNA cannot be translocated from the A to the P site, if the P site is occupied by deacylated tRNA. With the spontaneous translocation system, all reactions of the elongation cycle are cooperatively interconnected; i.e. upon binding of aminoacyl-tRNA to the A site, a significant portion of the ribosomes performs a complete round of the elongation cycle without the addition of elongation factor EF-G.

Escherichia coli↗
PubMed1984

[Comparative multicenter study of 2 methods of determining sensitivity to antibiotics. Gel diffusion method and semiautomatic method in fluid ABAC medium].

Susceptibility of 60 bacterial isolates to 15 antibiotics was determined by two methods in three laboratories: 48 Gram negative bacilli and 12 Staphylococci were selected because of "intermediate" susceptibility to at least one antibiotic. Results show a good correlation between the two methods: more than 90% for carbenicillin, cefazolin, cefoxitin, cefamandole, kanamycin, tobramycin, amikacin, erythromycin, pristinamycin and fusidic acid, between 80 and 90% for penicillin G, ampicillin, oxacillin, gentamicin, doxycycline, chloramphenicol, spiramycin and clindamycin, less than 80% for neomycin, tetracycline, minocycline and oleandomycin. Interpretation criteria are different in the two methods for rifampicin, colistin and cotrimoxazole. Between the three laboratories, correlation was 90,3% and 88,6% for disc diffusion method and ABAC system respectively.

Anti-Bacterial Agents↗
PubMed1983

A general survey of antibiotic treatment of staphylococcal septicaemia and endocarditis.

The penicillinase-resistant penicillins (methicillin, oxacillin, nafcillin) have been the mainstay of antibiotic therapy for S. aureus septicaemia and endocarditis. In experimental rabbit S. aureus endocarditis, these three antibiotics were equally effective. There has been no prospective comparative clinical studies to determine the relative effectiveness of these antibiotics. In experimental rabbit S. aureus endocarditis, cephalothin and cefazolin are less effective than methicillin and nafcillin. The results of therapy with cephalosporins in patients with S. aureus endocarditis are variable. Clindamycin therapy of S. aureus endocarditis has been associated with clinical relapse. Vancomycin has been used to treat S. aureus septicaemia and endocarditis with good results. Fusidic acid has been used in combination with another effective drug in treating S. aureus septicaemia and endocarditis. Although the combination of a cell-wall acting antibiotic with an aminoglycoside has been shown to have an enhanced anti-staphylococcal activity in vitro and in animal studies, there is no evidence that such a combination reduces morbidity or mortality clinically. Rifampin in combination with a cell-wall acting antibiotic is antagonistic against S. aureus in vitro and in experimental endocarditis in rabbits. The use of such a combination has not shown consistent benefits clinically. The clinical importance of tolerance (MBC/MIC greater than or equal to 32) of cell-wall acting antibiotics to S. aureus is not clear. It appears not to be important in animal studies. Cephalosporins appear not to be effective in the treatment of methicillin-resistant S. aureus infections. The treatment of choice of sepsis and endocarditis due to such strains is vancomycin which is effective against all strains of methicillin-resistant S. aureus.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Antibiotic treatment of staphylococcal septicaemia and endocarditis in a Swedish hospital.

In a retrospective study covering the years 1977 to 1981, the results of antibiotic treatment in 123 patients with staphylococcal septicaemia with or without endocarditis have been analysed. 80 patients (mean age 60 years) were non-drug addicts (Group I) and 43 (mean age 28 years) were drug addicts (Group II). Underlying conditions other than drug abuse were noted in 74 patients in Group I and in only 7 in Group II.S. aureus was isolated from 117 patients and S. epidermidis in 6, all of them in Group I. 91 strains were penicillinase producers, but all susceptible to isoxazolyl-penicillins. In Group I verified or highly suspected endocarditis was registered in 12 patients (15%), always left-sided, as against in 31 (72%) in Group II, of whom 25 had tricuspid valve engagement. In the multivariate pattern of antibiotic treatment 3 groups may be discerned; 1) Cloxacillin, alone (35 patients) or in a combination (57), 2) Penicillin G, alone (6) or in a combination (12), and 3) Lincomycin or clindamycin, a cephalosporin or co-trimoxazole, alone (4) or in combination (9). Additive agents were mostly an aminoglycoside or fusidic acid. Out of the 45 patients in the whole material who received single therapy 9 patients (20%) died, and out of the 78 patients who received combined therapy 13 patients (16.6%) died. In the cloxacillin group 11.8% died, compared to 35% who initially received other antibiotics. In 70 patients the initial therapy had to be changed, in 39 due to adverse drug reactions and in 31 due to therapeutic failures or for unexplained reasons. In these cases linco- or clindamycin, more rarely rifampicin or vancomycin, were used. In Group I, 20 patients (25%) died, 8 of them with endocarditis. Sequels, relapses or reinfections were noted in 21 (25%), and 39 (50%) had an uneventful course. In Group II, 2 patients (5%) died, both with endocarditis. Sequels, relapses or reinfections occurred in 11 (25%), and 30 (70%) had an uneventful course. From this unstructured material no definite conclusions can be drawn. However, the lower mortality rate in the cloxacillin group suggests this regimen to be superior. The addition of other antibiotics did not appear to influence the clinical outcome. There was a more favourable outcome in addicts than in non-addicts, despite the same general principles of antibiotic treatment. Thus, for the outcome the characteristics of the patient group seemed to have more influence than the choice of antibiotic treatment.

Adolescent↗
PubMed1982

The effect of antibacterial agents on the association between bacteria and leukocytes.

The effect of antibacterial agents on human lymphocyte chemotaxis, phagocytic capacity, protein synthesis and the relation between morphologic and functional changes induced by antibacterial agents was studied. A significant depression of chemotaxis measured with an agarose gel technique was detected when human leukocytes were incubated with fusidic acid and rifampicin in clinically obtainable concentrations. The newer, well absorbed tetracyclines depressed chemotaxis at high concentrations, but a less pronounced inhibition was detected with classical tetracycline. The incorporation by human neutrophils of 14C-leucine into a trichloroacid insoluble fraction was markedly depressed by the same antibiotics, and it is suggested that some antibiotics acting by inhibition of protein synthesis also affect chemotaxis of human neutrophils. Doxycycline, but not lymecycline, initially decreased granulocyte adherence to glass surfaces. After 20 min of incubation granulocytes treated with both doxycycline and lymecycline adhered in higher numbers than control cells. Human leukocytes incubated with tetracycline hydrochloride or doxycycline in vitro showed a decreased capacity to phagocytize yeast and bacteria. Furthermore, leukocytes harvested from healthy volunteers after ingestion of tetracycline also demonstrated decreased phagocytic capacity. Scanning electron micrographic studies showed changed surface morphology for granulocytes incubated with tetracyclines, which might explain the changed adherence and phagocytosis by tetracycline-treated cells.

Anti-Bacterial Agents↗
PubMedDate not supplied

Antibiogram and production of beta-lactamase by canine isolates of Staphylococcus aureus.

Clinical isolates of canine S. aureus strains (213) have been investigated for ability to produce beta-lactamase and sensitivity to 12 antibiotics. Fifty (23.5%) strains produced beta-lactamase. Using only the paper disc antibiotic diffusion method 17 of these would incorrectly have been classified was sensitive to beta-lactamase antibiotics. all strains were sensitive to methicillin, gentamicin and fusidic acid.

Animals↗
PubMed1980

Response of developing branched bacteria to adverse environments. I. Membrane-transfer techniques for assessment and SEM visualization of drug activity against Nocardia asteroides.

Membrane-transfer technique (MTT) is proposed as a method for assessing antimicrobial activity against branched bacteria at different phases of development. After preliminary cultivation up to the desired stage, colonies developing on membranes are transferred onto media containing various concentrations of drugs to be tested. Different exposure times and drug combinations are possible. Following exposure to the toxicant, membranes can be examined macroscopically, by light or electron microscopy and/or transferred to drug-free media to evaluate viability and possible recovery. Some results on the effects of benzylpenicillin, fusidic acid, gentamicin and sulfadiazine on the morphology of Nocardia asteroides, as detected by scanning electron microscopy, are presented. The progression of alterations, due to increasing exposures to various concentrations of gentamicin, has also been followed. Minimal inhibitory concentration values for the same antibiotic vary according to the growth phase; in particular in the early developmental stages they appear directly related. Advantages of MTT over classical "antigermination" tests in assessing susceptibility to different toxicants and its possible application to the study of environmental effects on morphogenesis of branched bacteria are discussed.

Anti-Bacterial Agents↗
PubMed1980

[Folliculitis decalvans].

The author describes the main clinical and pathological aspects of Folliculitis decalvans, rare dermatosis, probably related with Staphylococcus sensibilization of the follicle. Although in some cases Staphylococcus are present in the lesions, the treatment is disappointing. Tetracycline oral and topically, sodium sulfacetamide and fusidic acid are mentioned by Rook. Alopecia is always definitive.

Alopecia↗
PubMed1982

Epidemic of hospital-acquired infection due to methicillin-resistant Staphylococcus aureus in major Victorian hospitals.

During 1979, the Victorian Health Commission received reports of a rising proportion of methicillin-resistant Staphylococcus aureus (MRSA) isolates from an increasing number of institutions. At least 31 metropolitan hospitals were involved, and six of these reported MRSA totaling between 20% and 40% of all Staph. aureus isolates. Since that time, the problem has continued. In some university teaching hospitals, strains of MRSA now cause from 200 to 300 new cases of hospital-acquired infection each year. Sepsis occurs mainly in patients who underwent surgery, premature neonates and in the immunocompromised or debilitated patients. The organism involved is multiresistant. Recent isolates show increasing resistance, particularly against gentamicin, chloramphenicol and, more lately, fusidic acid and rifampicin. Only vancomycin can be relied upon for empirical treatment. There is concern that increasing use of vancomycin will select vancomycin-resistant strains of MRSA, so that, in the near future, there may no longer be any effective antibiotic therapy against hospital staphylococci.

Australia↗
PubMedDate not supplied

[Studies on the mechanism of translocation in ribosomes. V. Comparison of the effect of antibiotic inhibitors of ribosomes on "enzymatic" and "non-enzymatic" translation].

A comparison of the effect of 11 antibiotic inhibitors of protein synthesis on "enzymatic" and para-chloromercuribenzoateactivated "non-enzymatic" translation was made. It was found that fusidic acid which inhibits protein synthesis by blocking the action of one of the elongation factors (EF-G) did not suppress functioning of the "non-enzymatic" system. On the contrary, all the antibiotics blocking different functional sites of the ribosome itself such as tetracycline, chloramphenicol, erythromycin, edeine, thiostreptone, viridogrisein, spectinomycin, streptomycin, kanamycin and neomycin, were shown to inhibit the "non-enzymatic" translation. The data obtained corroborate the idea that the molecular mechanism which the ribosome utilized during "non-enzymatic" translation are similar or identical to the mechanism of normal "enzymatic" translation. It was found that the "non-enzymatic" working ribosome is more sensitive to all the antibiotics as compared to the ribosome synthesizing peptide with the participation of elongation factors (EF-T and EF-G). This suggests that the elongation factors increase the level of general resistance of the working ribosome against very different hindrances.

Anti-Bacterial Agents↗
PubMed1994

Time-kill efficacy of antibiotics in combination with rifampin against Staphylococcus epidermidis biofilms.

Infections associated with implants are frequently resistant to conventional antibiotic therapy. This resistance has been ascribed to the presence of bacteria on the artificial surface within a protective glue-like matrix forming a bacterial biofilm. We have demonstrated that experimental biofilms of Staphylococcus epidermidis, the main pathogen associated with implantation, are exquisitely sensitive to the action of rifampin. This effect of rifampin is incomplete, however, with the emergence of rifampin-resistant survivors that readily repopulate the biofilm. Studies were therefore performed to determine the effect of combinations of 13 different antibiotics with rifampin against standardized S. epidermidis biofilm preparations in an in vitro assay enabling the kinetic measurement of antibiotic action over a five-day period. The antibiotic combinations with rifampin demonstrated unsuspected divergent patterns of antimicrobial activity against the biofilms: 1. rapid synergy with rifampin was observed with cell-wall active antibiotics (cloxacillin, cephalothin, cefazolin, and cefamandole), whereas slower synergy occurred with vancomycin, ciprofloxacin, tetracycline, and amikacin; 2. some antibiotics (tobramycin, erythromycin, clindamycin, fusidic acid) did not influence the outcome; 3. gentamicin unexpectedly showed marked antagonism to rifampin. These results are relevant to the design of optimal therapeutic regimens for the management of resistant implant-associated infections.

Anti-Bacterial Agents↗
PubMed1994

Treatment of shunt-related cerebral ventriculitis due to Corynebacterium jeikeium with vancomycin administered intraventricularly. Case report.

A 52-year-old female with subarachnoid haemorrhage and hydrocephalus was treated with external and later internal drainage. She developed ventriculoperitoneal shunt-related ventriculitis caused by Corynebacterium jeikeium. The infection was unsuccessfully treated with intravenous vancomycin. It was controlled only after shunt removal and administration of intraventricular vancomycin as well as systemic vancomycin, rifampicin and fusidic acid. A review of the literature confirmed our experience that vancomycin given intraventricularly is well tolerated and doses can be individualized by measuring vancomycin levels in cerebrospinal fluid.

Catheterization↗
PubMed1994

Methicillin-resistant Staphylococcus aureus (mrsa) in a Malaysian hospital.

Between August 1990 to November 1991, 905 of 2583 (35.4%) isolates of Staphylococcus aureus were found to be methicillin-resistant in a general hospital in Malaysia. A detailed study of 539 of these isolates showed a high prevalence of methicillin resistant Staphylococcus aureus (MRSA) in the surgical/orthopaedic wards, paediatric wards and the special care unit. The yield of MRSA was highest from wounds/ulcers/skin swabs accounting for 64.2 per cent followed by 6.9 per cent in blood cultures. Vancomycin remains the drug of choice with no resistance detected. The resistance to ciprofloxacin was 6.7 per cent, rifampicin 4.5 per cent and fusidic acid 2.0 per cent. Most isolates were resistant to aminoglycosides. In view of the high prevalence of MRSA in this hospital, the authorities must introduce more effective measures to control its spread as a nosocomial pathogen. Otherwise it may seriously disrupt the efficient delivery of health care services in the country.

Adolescent↗
PubMed1993

[Evolution of resistance to antibiotics and antiseptics of hospital Staphylococcus aureus strains isolated from 1980 to 1991].

From 1980 to 1991, 925 non epidemic hospital isolates of S. aureus were selected and phage typed. MIC of 20 antibiotics and 4 antiseptics were determined by agar dilution method. The proportion of isolates susceptible to all antibiotics remains constant; however the trend to the resistance is strong during the study period (oxacillin 10-->20%, erythromycin 17-->28%, pefloxacin 4-->19%...). Strains resistant to oxacillin become more and more multiple resistant; some of recent isolates are resistant to 7 antibiotic families. There are very few products active against these strains i.e, glycopeptides (100%), pristinamycin (96%), fusidic acid (94%). This finding implies the need for continuous surveillance at the local and national level.

Aminoglycosides↗
PubMed1993

Epidemic methicillin-resistant Staphylococcus aureus (EMRSA): experience from a health district of central England over five years.

A series of outbreaks of EMRSA occurred in three hospitals of a Health District in the years 1986 and 1987, affecting 64 patients and 6 staff members. By the antibiotic sensitivity pattern (methicillin-resistance and resistance to many others) and phage typing, the organism resembled the epidemic strains involved in London outbreaks. In this series of outbreaks, different circumstances led to adaptation of different control measures with their cost implications. As failure with chlorhexidine was experienced, it was replaced with povidone-iodine for routine handwashing and topical application to patients in affected wards. Heavy environmental contamination involving mattress, bed, floor, table, chair, locker, television etc. was shown. Repeated failures of a phenolic disinfectant led to use of formaldehyde or a higher concentration of the phenolic disinfectant which caused side effects in staff members. Various anti-bacterial agents had been used in treating different conditions in different cases. Mupirocin was found to be the best agent in treating infections or colonization of superficial accessible sites. For non-accessible sites fusidic acid and rifampicin were found to be satisfactory. Continued surveillance in the District for three years after the last case did not detect re-emergence of EMRSA.

Aged↗
PubMed1993

In vitro antimicrobial susceptibility testing of rapidly growing mycobacteria using the tablet diffusion method: resistance pattern of Norwegian Mycobacterium fortuitum and Mycobacterium chelonae isolates.

Thirty-one Norwegian clinical isolates of rapidly growing mycobacteria classified as Runyon's group IV, including 20 Mycobacterium fortuitum and 11 Mycobacterium chelonae strains, were found resistant to a majority of tuberculostatic agents. Minimal inhibitory concentration (MIC) was determined for twelve other antimicrobial agents: amikacin, tobramycin, streptomycin, cefoxitin, imipenem, norfloxacin, ciprofloxacin, doxycycline, erythromycin, fusidic acid, co-trimoxazole and capreomycin. The agar plate dilution method was employed and compared with the agar tablet diffusion method. Regression lines were established correlating MIC values and inhibition zones. The agar tablet diffusion method was found to be a simple and useful method for testing antimicrobial susceptibilities of M. fortuitum and M. chelonae, and a good correlation between MIC values and zone sizes with twelve antimicrobial agents was revealed. Correlation coefficients for most of these antimicrobial agents were around -0.90. M. chelonae was generally more resistant than M. fortuitum. Four antimicrobial agents, capreomycin, norfloxacin, ciprofloxacin and amikacin, showed differences between M. fortuitum and M. chelonae large enough to allow the zone diameter to be used diagnostically.

Anti-Bacterial Agents↗
PubMedDate not supplied

Methicillin-resistant Staphylococcus aureus bacteraemia at a tertiary teaching hospital.

Between July and December 1994, 25 patients with MRSA bacteraemia were treated at the Hospital Kuala Lumpur, a tertiary hospital in Malaysia with 3000 beds. The patients included 15 males and 10 females whose mean age was 46.7 years (range 13-75). The sources of their MRSA were: Urology/Nephrology, 11; General ICU, six; Orthopaedic, four; Medicine, three; Surgery, one. Their underlying diseases were: end-stage and chronic renal failure, 11; burns, three; acute necrotising pancreatitis, two; haematological malignancies, two; and one each of fracture of the neck of the femur, pustular psoriasis, alcoholic cirrhosis, liver abscess, peptic ulcer (antrectomy), choledochol cyst, and abdominal aneurysm with gangrene of the legs. Six patients were also diabetic. A total of 19 infections were considered nosocomial. The duration of hospital stay ranged from one to 60 days, mean 16 days. On the day of blood culture, 20 patients (80%) were febrile and 15(60%) had leucocytosis. A total of 14 patients were considered to have received prolonged broad-spectrum antibiotics before the bacteraemia; of these, 11 had had either a third-generation cephalosporin and/or a quinolone. The primary foci of infection were: vascular access dialysis catheters, six; infected AV fistulae, three; non-surgical wounds, five; orthopaedic pin, one; multiple venous lines and catheters, nine; unknown, one. The sensitivities to anti-MRSA antibiotics were: vancomycin, 100%; fusidic acid, 96%; rifampicin, 96%; ciprofloxacin and perfloxacin 28% each. In all, 13 patients (52%) eventually died; nine of these deaths were directly attributed to MRSA bacteraemia. The microbiological eradication rate was 88%. Mortality was significantly associated with duration of hospital stay and failure to remove the infected catheters/peripheral lines after the development of MRSA bacteraemia.

Adolescent↗
PubMed1996

[Typing, resistance behavior and occurrence of methicillin-resistant Staphylococcus aureus strains in a surgical intensive care unit].

Over a period of three years, the frequency of the appearance of methicillin-resistant S. aureus strains (MRSA) was observed on a surgical intensive care unit. During this above-mentioned period of investigation it came to a heaped occurrence of nosocomial infections on this ICU with altogether 332 S. aureus-stems being isolated from different patient specimen. 204 (61.5%) of these were resistant against methicillin and could be divided into 48 first- and 156 follow-up-isolates. The thereupon accomplished differentiation of the 48 MRSA-first isolates by means of lysotyping and the pioneered GenePath Strain Typing System for a standardized pulsed-field-gel-electrophoresis (PFGE) gave the proof of 7 different MRSA-types. Around 7 different, in part parallel chains of infection on this ICU were observed, which could be led back to different strains. In reference to all analyzed S. aureus, an especially high rate (90%) of MRSA on this ICU could be isolated in taken wound-swabs, followed by 83.3% MRSA at catheter tips and 71,9% in tracheal and bronchial secretion. A consideration of the antibiotic susceptibility yielded, that also gentamicin and the quinolones showed an in-vitro resistance against MRSA, while fosfomycin, fusidic acid, chloramphenicol and trimethoprim/sulfamethoxazole reached positive responding rates between 80 and 100%. On the other hand, presently still 100% of the explored MRSA-strains are susceptible for glycopeptides such as vancomycin and teicoplanin. Because of intensive hospital hygienic measures the number of newly isolated MRSA could be reduced clearly on this ward.

Anti-Bacterial Agents↗