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Arthroscopic debridement and irrigation of periprosthetic total elbow infection.

We report on a case of arthroscopic treatment of septic arthritis of the elbow joint in a 65-year-old man with an elbow endoprosthesis. Two months after arthroplasty of the elbow joint, the patient developed acute septic arthritis of the right elbow. Methicillin-sensitive Staphylococcus aureus was identified as the causative organism. Six days after the onset of symptoms, the patient was treated with a single arthroscopic procedure of the infected periprosthetic joint, including irrigation with 5 L of Ringer's lactate solution, debridement, and partial synovectomy with a 4.5-mm curved shaver. Intravenous antibiotic therapy was also used for 3 months including rifampicine and fucidic acid according to the intraoperative cultures. The acutely infected total elbow arthroplasty could be cured without removal of the endoprosthesis of the elbow. Ten months postoperatively, the patient remains free of symptoms and his blood rates are within normal limits.

Aged↗

Pharmacokinetic interaction of antimicrobial agents with levomethadon in drug-addicted AIDS patients.

Morphine and its derivatives are metabolized by the liver microsomal enzyme system with a high first-pass effect after oral application. In four of 44 HIV-infected i.v. drug abusers who participated in a levomethadon maintenance program, we observed sustained symptoms of under-dosage and loss of effect of there to fore well-tolerated substitution therapy during rifampin treatment or therapy with zidovudine or fucidic acid. As a pharmacological model substance for cytochrome p 450 enzymes, measurement of antipyrine in serum by high pressure liquid chromatography revealed induction of cytochrome p 450 isoenzymes. The half-life of antipyrine decreased (patient 1 from 11.3 to 8.4 h and patient 2 from 10.7 to 7.6 h after rifampin, patient 3 from 12.2 to 8.6 h after fucidic acid, and patient 4 from 10.6 to 8.6 h after zidovudine). In i.v. drug abusers on levomethadon maintenance programs, adjustment of the levomethadon dosage may be necessary when specific therapy for HIV infection and associated diseases requires the use of drugs known to be potent inducers of the liver microsomal enzyme system.

Acquired Immunodeficiency Syndrome↗

Vaginal absorption of insulin in the rat: effect of penetration enhancers on insulin uptake and mucosal histology.

The absorption of insulin across the vaginal mucosa into the systemic circulation was studied in ovariectomized rats given subsequent estrogen treatment. Blood glucose levels were determined as an indirect measure of insulin absorption, and the effect of various enhancers on the hypoglycemic response was investigated. In the absence of any enhancer, no decrease in blood glucose levels was observed after vaginal administration of insulin. However, the coadministration of sodium taurodihydrofusidate, polyoxyethylene-9-lauryl ether, lysophosphatidylcholine, palmitoylcarnitine chloride, and lysophosphatidylglycerol significantly increased hypoglycemia, whereas citric acid had little effect. The histological changes in the vaginal epithelium after treatment with the enhancer systems were variable and often severe. While the efficacy of these compounds in promoting the vaginal absorption of insulin is encouraging, their mechanisms of action and long-term histological effects are yet to be defined.

Absorption↗

[Characteristics of fucidin biosynthesis by a Fusidium coccineum 257 A strain].

The physiological features of Fusidium coccineum, strain 257 A, an organism producing fusidin were studied. It was found that increased concentrations of the carbon sources in the medium stimulated production of fusidin, while an increase in the content of various forms of nitrogen differently affected the level of the antibiotic viosynthesis: high concentrations of the amino acid-peptide form of nitrogen of corn-steep liquor decreased, while the protein form of nitrogen was associated with consumption of the significant part of carbon in the medium for formation of the fungus mycelium. Therefore, the concentration of the easily mobilizing forms of nitrogen may be considered as a regulator of the growth process of F. coccineum 257 A and production of fusidin by it.

Carbohydrate Metabolism↗

Site of action of ricin on the ribosome.

The extent of the inhibitory effect of ricin in polyphenylalanine synthesis by eukaryotic ribosomes is strongly dependent upon the concentration of ribosomes and the elongation factors EF 1 and EF2. Maximal inhibition by ricin, in this assay is observed when either ribosomes or the two elongation factors are added under limiting conditions, whereas ricin-treated ribosomes support protein synthesis at saturating concentrations of elongation factors and ribosomes. Similarly, the enzymatic binding of Phe-tRNA to ribosomes is drastically blocked in ricin-treated ribosomes when low EF 1 concentrations are added to the reaction mixture, but there is no inhibition when EF 1 is at saturating concentrations. Furthermore, formation of the complex EF 2-guanosine triphosphate-ribosome, using free ribosomes pretreated with ricin, is strongly inhibited at limiting concentrations of EF2, but is not affected at saturating concentrations of this factor. However, ricin does not inhibit the EF 2-dependent translocation of peptidyl-tRNA by polysomes, although the toxin is very active in preventing amino acid incorporation by polysomes. Our results suggest that the damaging effect of ricin on the ribosome causes a decreased affinity for both elongation factors EF 1 and EF 2. Thus, the toxin inhibits the enzymatic binding of aminoacyl-tRNA to ribosomes. The lack of inhibition of translocation by ricin suggests that the toxin cannot interact with ribosomes with substrate bound to the acceptor site. Essentially similar results are observed with ricin, abrin, ricin A chain, abrin A chain, and ricinus agglutinin A chain. A possible effect of the toxins on initiation and/or termination is further discussed.

Abrin↗

[Severe infections caused by methicillin-resistant Staphylococcus aureus. 62 cases].

A French multicentre study was conducted in 15 Infectious Diseases departments; 347 cases of severe staphylococcal infections were collected during one year (October 1989 to October 1990): Two-hundred and fifty-eight strains were analysed with complementary bacteriological studies, including 62 strains of methicillin-resistant Staphylococcus aureus. Epidemiological, clinical and therapeutic aspects were investigated. Nosocomial infection was responsible for 90 percent of the cases, and previous antibiotic therapy was reported in 74 percent. An invasive procedure was incriminated in 43 patients (69 percent); intravenous catheter (38 percent), mechanical ventilation (31 percent), surgery (22 percent), prosthetic device (20 percent). Thirty-nine patients were treated with glycopeptides either alone or in combination with beta-lactams, aminoglycosides, fucidic acid, fosfomycin, rifampicin, quinolones or synergistines, showing the great diversity in the choice of antibiotics in methicillin-resistant S. aureus infections. More than 90 percent of these strains were resistant to gentamicin and quinolones, 80 percent of clindamycin and 70 percent to rifampicin. No resistance to glycopeptides (vancomycin or teicoplanin) was observed. Prognosis was severe, with a mortality rate of 35 percent, justifying educational and prophylactic measures in at risk medical departments.

AIDS-Related Opportunistic Infections↗

Biological and molecular variability of Sarocladium oryzae, the sheath rot pathogen of rice (Oryza sativa L.).

Sheath rot disease of rice caused by Sarocladium oryzae (Sawada) (=Acrocylindrium oryzae, Sawada) has become an important production constraint in all rice-growing countries. Pathogenicity, phytotoxic metabolites, and random amplified polymorphic DNA (RAPD) markers were used to assess the level of genetic variability of S. oryzae derived from rice cultivars, CR1018, IR36, and IR50, of different locations in North East and South India. Variability in pathogenicity, phytotoxic metabolite production, and DNA polymorphisms was detected among S. oryzae isolates. Results indicated that S. oryzae isolates produced both cerulenin and helvolic acid at concentrations 0.3-0.62 and 0.9-4.8 microg mL(-1) of culture filtrate, respectively. Isolates that produce higher concentration of helvolic acid induced a high percent incidence of sheath rot disease. Oligonucleotide primers, GF and MR, generated either a simple (up to 2 bands) or complex (up to 6 bands) RAPD pattern. According to their level of similarity, S. oryzae isolates from North East and South India were grouped separately into two major clusters and 13 genotypes. Molecular- and pathogenicity-based classifications were not correlated, but a high level of genetic variability within S. oryzae isolates was identified. The molecular variability of S. oryzae isolates will be an important consideration in breeding programs to develop durable resistance for sheath rot disease.

Ascomycota↗

RNA-metabolism in Streptomyces hydrogenans. Effect of 20beta-hydroxysteroid-dehydrogenase inducing dienediol on RNA-content and RNA-profile.

For the isolation of RNA and polysomes, logarithmically growing cells were disrupted by grinding with kieselgur. Other methods failed to produce undergraded m-RNA as shown by 10-50% sucrose gradient-centrifugation and electrophoresis in 2% mixed agarose-acrylamide gel columns. RNA was extracted by a modified phenol method or in presence of DEP. After the application of dienediol, the amount of acid precipitable RNA decreased by 20 to 50% in 20 min. Incorportation of precursors into RNA was much slower immediately after induction but increased during the next two hours. Three hours after induction there was no difference in the RNA-content of induced and control cultures. Degradation of stable as well as of unstable RNA was observed. Simultaneous addition of the inducer and rifamycin inhibited the production of 20beta-STDH suggesting the synthesis of special m-RNA. The effects of some other antibiotics have also been studied. The existence of a specific m-RNA in the induced system was established from differences in the 3H/14C quotients of gel fractions in the region between light r-RNA and t-RNA.

Cortisone Reductase↗

Epidemiosurveillance of antimicrobial compound resistance of Staphylococcus intermedium clinical isolates from canine pyodermas.

In a retrospective study, 131 Staphylococcus intermedius strains isolated from apparently healthy dogs, and 187 Staphylococcus intermedius strains isolated from dog pyodermas in the clinical microbiology laboratory at the National Veterinary School in Nantes, during three successive periods: 1986-87, 1992-93 and 1995-96, were investigated and compared for their antimicrobial susceptibility. Results indicated that 60% to 65% of the strains were susceptible to Chloramphenicol and Doxycyclin, 65% to 80% of the strains were susceptible to macrolides (Erythromycin, Lincomycin and Clindamycin) and to Trimethoprim/Sulfonamide association. More than 95% of the strains were susceptible to three betalactamins tested: Oxacillin, Amoxycillin/Clavulanic acid, Cephalexin, to Gentamicin, to Fucidic Acid and to two quinolones: Enrofloxacin and Marbofloxacin. This last group is made up of choice antibacterials for the treatment of dog pyoderma. Many different resistance patterns were observed in each period with no really predominant profile, because of low plasmidic vs chromosomal balance of the genetic basis of antibacterial resistance in Staphylococcus intermedius. However, the proportion of multiresistant (> or = 3 drugs) strains increased from 10.8% in the first period, to 28% in the third period. This increased frequency of resistance suggests strongly that, as in Staphylococcus aureus human infections, the prescription of antibiotic compounds increases the prevalence of resistant strains.

Aminoglycosides↗

[Carbohydrate and pyruvic acid degradation pathways in Fusidium coccineum strains with varying levels of antibiotic synthesis].

A number of enzymes and reactions of glycolysis, pentose-phosphate cycle and degradation of pyruvic acid in strains of F. coccineum with various levels of antibiotic production was studied comparatively. The experiments showed that highly productive strains were characterized by higher activity of the NADP-deficient enzymes of the pentoze-phosphate cycle as compared to the low active strains. The activity levels of glycolytic enzymes, such as fructose-diphosphate-aldolase and 3-phosphoglycerolaldehydehydrogenase did not practically differ. Significant differences were found in the reactions of puryvic acid degradation: the activity of cytoplasmic pyruvatedecarboxylase in the mutant with high antibiotic production level was lower than that in the low productive strain, while oxidation of the pyruvate of the mitochondrial fraction was on the contrary more intensive than in the highly productive strain. Therefore, metabilism in the strains studied was characterized by ever-increasing biochemical changes with an increase in their antibiotic productivity. Lowering of the growth rate of the mutants as their capacity for antibiotic supersynthesis increased and subsequently the anabolic processes became more intensive was accompanied by increasing derepression of the key enzymes of carbohydrate metabolism and in particular NADR-deficient dehydrogenase of the pentose cycle and pyruvatedehydrogenase, significant for fusidin biosynthesis and providing production of the antibiotic of steroid nature by cofactor NADP-H and acetyl-KoA, the primary precursor.

Anti-Bacterial Agents↗

Surveillance of antibiotic resistance in ICUs in southeastern Sweden. ICU Study Group of the South East of Sweden.

BACKGROUND: A study was designed to assess a computer-based program for continuous registration of antibiotic resistance, statistics concerning severity of illness, and consumption of antibacterial drugs. METHODS: The frequency of antibiotic resistance among bacteria in eight ICUs in southeastern Sweden was investigated yearly from 1995 through 1997. The antibiotic consumption in the ICUs was registered as defined daily doses (DDD) and compared to severity of illness (APACHE-II scores). RESULTS: There was a statistically significant increase in ampicillin resistance among Enterococcus spp. between 1996 and 1997, which was due to a shift from Enterococcus faecalis to Enterococcus faecium. A high prevalence of resistance among coagulase-negative staphylococci to oxacillin (approximately 70%), ciprofloxacin (approximately 50%), fucidic acid (approximately 50%) and netilmicin (approximately 30%) was seen in all ICUs during the whole study period. There was a statistically significant increase in ciprofloxacin resistance among Escherichia coli and Enterococcus spp. The resistance among Enterobacter spp. to cefotaxime decreased but this change was not statistically significant. Efforts were made to avoid betalactam antibiotics, except carbapenems, for treatment of infections caused by Enterobacter spp. and the consumption of cephalosporins decreased whereas the consumption of carbapenems increased. The total antibiotic consumption decreased by 2.5% during the study period. There was no correlation between APACHE II scores and antibiotic consumption. CONCLUSIONS: Each ICU within a hospital ought to have a program for "on-line" antibiotic resistance surveillance of drugs used in that unit so that changes in empirical treatment can be made when there is an increase in antibiotic-resistant isolates within that unit.

APACHE↗

Polypeptide-chain elongation promoted by guanyl-5'-yl imidodiphosphate.

In a purified system from Escherichia coli containing ribosomes complexed with poly(uridylic acid) and N-acetyl-phenylalanyl-tRNA, the nonhydrolyzable analog of GTP, guanyl-5'-yl imidodiphosphate (Guo-5'-P2-NH-P), promotes polypeptide synthesis at a rate several times slower than GTP. The activity is completely dependent on elongation factors EF-T (i.e, EF-Ts + EF-Tu) and EF-G. Examination of individual steps of the elongation cycle in partial reactions shows that Guo-5'-P2-NH-P is as efficient as GTP in promoting the EF-T-dependent binding of phenylalanyl-tRNA to the ribosomal A site. In contrast, Guo-5'-P2-NH-P promotes the translocation-dependent binding of phenylalanyl-tRNA to a ribosome complexed with A-site-bound N-acetyl-phenylalanyl-tRNA much more slowly than GTP. This slow rate of binding is due to the presence of EF-G on the ribosome, and not to sluggish translocation, since (a) the rate remains slow even after translocation of N-acetylphenylalanyl-tRNA is completed, (b) it is greatly speeded up by removal of EF-G from the reaction mixture (after translocation has occurred), and (c) it is slowed down again by readdition of the factor. Moreover, with post-translocated ribosomes and in the absence of EF-G, formation of dipeptide subsequent to the EF-T-dependent binding of phenylalanyl-tRNA is much slower when binding of this substrate has been promoted by Guo-5'-P2-NH-P than it is when promoted by GTP. The results suggest that, during polymerization with Guo-5'-P2-NH-P, EF-G and EF-Tu are slowly released from the ribosome and, consequently, the steps of the elongation cycle subsequent to translocation and aminoacyl-tRNA binding (aminoacyl-tRNA binding and peptide bond formation, respectively) are delayed. Thus, durong elongation cycle, GTP hydrolysis is probably essential for fast release of the factors from the ribosome.

Binding Sites↗

Staphylococcal infection of open granulating wounds.

The significance of staphylococcal infection has been studied prospectively in 250 wounds healing by open granulation. In a series of 50 axillary skin excisions, 17 became infected with Staphylococcus aureus with consequent pain and delay in healing. The infections responded well to Fucidin ointment. Nasal carriers of the organism may be especially liable to this complication. In contrast, although S. aureus was not infrequently found in deep granulating wounds, there was no clear evidence of harm resulting in the 50 laparotomy wounds and 150 pilonidal sinus excisions studied. The susceptibility of superficial wounds to the infection is ascribed to friction from dressings. Deep granulating wounds are occasionally affected similarly when the cavity has filled.

Axilla↗

Ultracentrifugal study of effect of sodium chloride on micelle size of fusidate sodium.

Apparent micellar molecular weights were determined with the antibiotic fusidate sodium by ultracentrifugation in varying counterion concentrations (Na+). The effects of buffer salts, pH, sodium chloride concentration, and drug concentration were studied. The results strongly support the concept of the formation of primary micelles composed of five monomer units, followed by aggregation of the pentomers into larger micelles as salt concentration increases.

Buffers↗