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PubMed1990

Topical antibiotic therapy: current status and future prospects.

As we enter a new decade, topical antibiotics are the subject of much renewed interest and are being used on a wider scale than ever before. The reasons for using topical rather than oral therapy for a variety of dermatoses include the reduced risk of systemic side effects, the avoidance of resistance selection in the gut microflora, the higher achievable concentration of antibiotic at the site of action and the overall usage of less drug. Somewhat surprisingly, treatment costs are not reduced by the use of topical therapy. The number of antibiotics licensed for topical use has increased in recent years and now includes representatives of the tetracycline, macrolide, lincosamide, aminoglycoside and peptide families of antibiotics in addition to fusidic acid, chloramphenicol and pseudomonic acid. Opinions regarding the clinical efficacy of topical antibiotics are conflicting, and for most indications alternative oral therapies are available. Topical antibiotics are the drugs of choice for the elimination of nasal carriage of Staphylococcus aureus and for the therapy of eye and external ear infections. They are also effective in the treatment of impetigo and other superficial pyodermas and in the management of localised infected eczema. Topical preparations of erythromycin, clindamycin and tetracycline are widely prescribed for the therapy of acne and are of clinical benefit in mild--moderate cases. However, they are no more effective against inflamed lesions than benzoyl peroxide and are less effective against non-inflamed lesions. They are not as effective as oral tetracycline in moderate to severe acne and should not be considered as a therapy for severe acne, for which 13-cis-retinoic acid is the drug of choice. It is well known that many antibiotics, when used topically, especially for prolonged periods, select for antibiotic-resistant staphylococci at the skin surface. Tetracyclines, erythromycin and clindamycin also select for resistant staphylococci on the surface of intact skin when delivered by the oral route. The contribution of topical antibiotic usage to the current high level of antibiotic resistance in coagulase-negative staphylococci, which are increasingly implicated in infections of compromised hosts, has not been quantified, although it is known that cutaneous staphylococci possess a large pool of transferable resistance genes.(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Topical↗
PubMed1990

[Sensitivity curves of multiply resistant corynebacteria JK and D2].

Corynebacteria groups JK and D2 are opportunistic pathogens. They are sometimes responsible for severe infections, especially in immunocompromised patients. They are resistant to many antibiotics. Under these conditions it seemed important to discover which antibiotics among those regularly active, have a killing effect, what their bactericidal speed is, and how they react to combination with other antibiotics. Glycopeptids have a killing effect within 24 hours. Pristinamycin, rifampin, fusidic acid, when active, are bacteriostatic. Their combination with vancomycin is indifferent but in one case the combination vancomycin + rifampin is synergistic.

Anti-Bacterial Agents↗
PubMedDate not supplied

[Sensitivity to antibiotics of bacterial strains isolated from clinical specimens during the years 1985-1986].

Sensitivity of 312 strains of staphylococci, 386 strains of streptococci and 1193 strains of aerobic gram-negative bacilli to the selected antibiotics was tested. These strains were isolated from the clinical material at the Clinical Hospital No. 1 in Warsaw within 1985-1986. Staphylococci were sensitive to pristinamycin, cefazolin, fusidic acid, oxacillin, and clindamycin. In 1986, a decrease in the number of strains sensitive to these antibiotics, except cefazolin, was seen. In case of streptococci the most active proved chloramphenicol and gentamicin but a significant decrease in the percentage of sensitive strains was also noted in 1986. The highest number of gram-negative bacilli was sensitive to amikacin, colistin, nalidixic acid, pipemidic acid, and gentamicin. In 1986, a decrease in the percentage of sensitive strains was noted. Amikacin and colistin were the most active against Pseudomonas spp. while amikacin and nalidixic and pipemidic acids--against Proteus spp. Comparison of the results with those obtained in 1981-1984 has shown that the sensitivity of staphylococci changed the most significantly and this change was unfavourable. Gentamicin and amikacin remained the most active against gram-negative bacilli while amikacin and colimycin against Pseudomonas spp. In case of anaerobes the majority of strains was sensitive to chloramphenicol, tetracycline and clindamycin. Metronidazole was active against high percentage of Clostridium spp. and all gram-negative bacilli while the percentage of gram-positive bacilli and cocci was sensitive to metronidazole.

Anti-Bacterial Agents↗
PubMed1989

Methicillin-resistant Staphylococcus aureus: an increasing threat in New Zealand hospitals.

During the three years 1985 to 1987 an increasing number of methicillin-resistant Staphylococcus aureus (MRSA) strains were identified in New Zealand each year. A total of 66 strains of MRSA were identified among isolates received from 418 patients and health personnel. The majority (337/418, 80.6%) of the isolates were from two independent large outbreaks of MRSA. All strains of MRSA were sensitive to vancomycin, rifampicin and fusidic acid. An overseas origin, usually Australia, was identified for 48.4% of strains. The majority of isolates were from patients whose host defences had been breached. Postoperative and cutaneous wounds were the commonest sites of acquisition.

Anti-Bacterial Agents↗
PubMed1989

[Chronic bone infections after surgery. Treatment with the new quinolones].

A prospective open study carried out over 5 years and including 20 patients suffering from chronic bone suppuration following orthopaedic surgery has confirmed the value of the new quinolones (NQ) in these indications. The patients received pefloxacin or ciprofloxacin most often combined with rifampicin or fusidic acid for a mean period of 7 months. Single or multiple organism infections were documented in 14 patients, the majority being Staph. aureus (n = 13) and Pseudomonas (n = 14). Samples were sterile in 6 cases. Fourteen therapeutic successes and 5 failures were observed. In one patient, improvement was noted but the post-treatment follow-up insufficient to pronounce a cure. Success was obtained in 14 out of 16 patients who had sensitive organisms or sterile samples. The mean post-treatment follow-up (16 months) was satisfactory but insufficient to speak of cure. However, in these patients for whom further surgery, however desirable, is often refused, NQ constitute an improvement which raises hopes of cure or allows further surgery.

Adult↗
PubMed1989

Blood cultures: eight years' experience of a conventional in-house system and trends in antimicrobial susceptibilities.

In a prospective analysis of 4234 significant isolates from 62,437 consecutive sets of blood cultures over an 8 year period, 79.4% were detected within 48 h. Routine examination of Gram-film smears made within 24 h of receipt of the cultures detected about half of all positive cultures. Many organisms were detected earlier on Castaneda slopes than in tryptone soya broth. Haemophilus influenzae (type b) and Neisseria spp. were usually suspected on clinical grounds, and early blind subculture was successful in 95.7% and 69% of cases respectively. Resistance to trimethoprim among Gram-negative coliforms increased significantly over the 8 year period. Production of beta-lactamase was detected in 12% of Haemophilus influenzae (type b). Unlike Staphylococcus aureus, Staphylococcus epidermidis was commonly resistant to methicillin, erythromycin, fusidic acid and gentamicin.

Blood↗
PubMed1988

[The action of combinations of the nonapeptide polymyxin B with antibiotics on gram-negative bacteria].

Activity of polymyxin B nonapeptide alone and in combination with other antibiotics against clinical strains of Pseudomonas and enteric bacteria was studied. It was shown that nonapeptide was highly active against Pseudomonas and moderately active against enteric bacteria. In combination with rifampicin, fusidic acid or erythromycin the nonapeptide had a potentiating effect on the tested strains.

Anti-Bacterial Agents↗
PubMed1986

Molecular aspects of cytoprotection by modified somatostatins.

Somatostatin and cyclic modifications of this molecule inhibit the development of protrusions on the surface of isolated hepatocytes in presence of phalloidin. This prevention of phalloidin injury is caused by competitive inhibition of the phallotoxin uptake. Transport inhibition is not a hormonal effect of somatostatin. The concentrations needed are in the micromolar range. The most protective somatostatin modifications lack hormonal activity (GH release). Somatostatin and its analogs are substrates of a hepatocellular transporter which also translocates other cyclopeptides, among them phalloidin, antamanide, and several organic anions, such as iodipamide and fusidic acid. Physiological substrates of this multispecific transport system are bile acids. The protection of phallotoxin injury by somatostatin is a specific mechanism only representative for liver cells. No other cell contains the above multispecific transporter.

Affinity Labels↗
PubMed1988

[Urinary Corynebacterium group D2 infections. A hospital epidemic and antibiotic sensitivity].

An outbreak of Corynebacterium group D2 urinary tract infections was recently observed at Nice CHR. These infections were characterized by alkaline urine. The five first cases were reported in the same department and the ten other cases were latter observed in different departments. Age average was 79 and all patients had either an intra-vesical catheter of a urinary collector. Among samples of material tested, only one gave a positive culture. The 15 isolates showed a similar identification and antibiotic phenotype. These strains presented a multiple antibiotic resistance: resistance to beta-lactams, aminoglycosides (except streptomycin), erythromycin, chloramphenicol, tetracyclines. All strains were susceptible to rifampin, pristinamycin, fusidic acid and vancomycin.

Aged↗
PubMed1977

Dissimilarity in protein chain elongation factor requirements between yeast and rat liver ribosomes.

Factor requirements for yeast and rat liver ribosomes were determined in several different reactions using either yeast or liver factors. In polymerization assays yeast ribosomes required a factor in addition to elongation factor 1 (EF-1) and elongation factor 2 (EP-2). The third factor (EF-3) requirement was observed with EFs from either yeast or liver for both poly(U)-directed polyphenylalanine synthesis and elongation of endogenous peptidyl-tRNA. No significant effect of EF-3 was observed with liver risomes in either assay. In contrast to results with polypeptide synthesis EF-3 was not required for EF-1 dependent binding of [3H]Phe-tRNA or the translocation-dependent formation of N-acetylphenylalanylpuromycin. Up to 2-fold stimulation of the binding reaction was observed with saturating levels of either yeast or liver EF-1. No effect of EF-3 was observed on ribosome-EF-2-GDP-fusidic acid complex formation. The data suggest that the yeast EF-3 may be a loosely bound ribosomal protein which is not required for a specific step in the elongation cycle but is involved in the coordination of the partial reactions required for polymerization.

Animals↗
PubMed1987

Changes in expression of bacterial surface antigens induced by antibiotics and their influence on host defenses.

Concomitant with the discovery that a number of antibiotics were able to induce profound morphological changes (increased septation, thickened walls, filamentation) at low concentrations their ability to inhibit bacterial protein/polysaccharide synthesis was determined. In particular toxin and extracellular enzyme biosynthesis could be repressed by the lincosamines, fusidic acid, erythromycin and streptomycin in Staphylococcus aureus, Streptococcus pyogenes, Propionibacterium acnes, Pseudomonas aeruginosa and Escherichia coli. Several of these exoproducts act as antigens associated with microbial virulence and are therefore of importance in pathogenicity. Likewise structural components such as fimbriae in Escherichia coli, M protein in Streptococcus pyogenes, protein A in Staphylococcus aureus and capsule in Bacteroides fragilis and Haemophilus influenzae were not synthesised when the producer bacteria were grown in low concentrations of antibiotic. These products, through their importance as impedins of opsonization and subsequent phagocytosis by white blood cells, are important determinants in the host-parasite relationship. By their loss during drug exposure, potentiation of opsonophagocytosis occurred leading to more rapid killing of the pathogen. The immunogenicity of the antibiotic-damaged bacteria was also changed under these circumstances.

Anti-Bacterial Agents↗
PubMed1988

[Characterization of methicillin-resistant Staphylococcus aureus strains isolated from 1974 to 1983 in West Germany with respect to the results of lysotyping].

A total of 594 methicillin-resistant (MER) S. aureus strains originating from the Federal Republic of Germany were both tested for their susceptibility to a number of selected antimicrobial agents, and lysotyped with the international set of S. aureus typing phages. Control groups of methicillin-sensitive, but penicillin- (PER) and gentamicin-resistant (GER) strains were tested for comparison. A group of S. aureus strains susceptible to all of the agents tested was included in the statistical evaluation of the lysotyping results. 98% of the MER and 72% of the GER S. aureus strains were cross-resistant towards at least five of the other agents tested. 84 to 97% of the MER strains were resistant to erythromycin, tetracycline, kanamycin and gentamicin. The in vitro susceptibility towards lincomycin and amikacin was in the range of 50 to 60%. The strongest in vitro efficacy--both against the MER and the GER strains--was shown by vancomycin and fusidic acid. 52.9% of the MER and 47% of the GER strains, but only 12.3% of the non-resistant strains and no more than 15% of the PER strains belonged to phage-group III; a higher proportion of these latter groups reacted with phage-group I, which was rare among the MER and the GER strains (3.2% and 7.8% respectively). The most frequent phage-patterns of the MER strains were as follows: 47/75/77, 47/54/75/77/84/85, 77/84/85, 47/54/75/77/85, 6/47/54/75/77/84/85, and 55/83A. Most of the phage-group III lysotopes occurred at numerous places across the country, while mixed lysotypes were apparently more confined to certain areas. A relatively high percentage of the MER strains, but notably also of the sensitive strains was non-typable (22.1% and 24.1% respectively), whereas the PER and the GER strains had a considerably lower rate of non-typability (9.3% and 4.8% respectively). A correlation between non-typability and multiresistance was not evident.

Anti-Bacterial Agents↗
PubMed1986

[Sensitivity of 858 strains of staphylococci to 27 antibiotics].

Susceptibility to 27 antimicrobial agents of 858 strains of staphylococci was determined. Tested strains belonged to the following species: S. epidermidis, S. saprophyticus, S. haemolyticus, S. hominis, S. simulans, S. warneri, S. cohnii, S. xylosus and S. intermedius. The antibiotics were: penicillin G, amoxycillin, augmentin, oxacillin, streptomycin, kanamycin, tobramycin, dibekacin, amikacin, gentamicin, sisomycin, netilmicin, doxycycline, minocycline, chloramphenicol, erythromycin, josamycin, clindamycin, pristinamycin, rifampin, fusidic acid, fosfomycin, trimethoprim, sulfamethoxazole, cotrimoxazole, and vancomycin. The ATB system was used, with the criteria for categorization recommended by the Antibiotic Sensitivity Testing Committee. Penicillin-resistance, that was found in all species, was high for hospital-acquired strains (67 to 75%) but also for some other strains (32% for S. simulans). Oxacillin-resistance varied across species (0% for the least prevalent hospital strains, 6% for S. epidermidis and 28% for S. haemolyticus). All strains were susceptible to vancomycin. For some drugs, resistance was a characteristic of the species: resistance to fosfomycin was often found for S. saprophyticus, S. haemolyticus, S. warneri, S. cohnii, and S. capitis; resistance to trimethoprim was common for S. simulans, and S. haemolyticus. S. haemolyticus was the most resistant species, a fact that justifies routine identification of this pathogen in clinical specimens.

Anti-Bacterial Agents↗
PubMed1978

Penetration of antimicrobials into tissue culture cells and leucocytes.

When exposed to HeLa cells in tissue culture for 72 hr., antimicrobials could be categorised into three groups characterised by cell associated concentrations much lower (ampicillin, cephalexin, cloxacillin, flucloxacillin, streptomycin and trimethoprim, all 14% or less), much higher (tetracycline and polymyxins) or approximating to those extracellularly (erythromycin, lincomycin, fusidic acid and gentamicin). For kanamycin, neomycin and sulphonamides, cell associated levels were between 24 and 47% and for penicillin G and cephaloridine were 66% of those extracellularly. With mouse peritoneal macrophages and human peripheral blood leucocytes cell associated levels for representative antibiotics were all lower after 3 hr. exposure than in the tissue culture cells. However, studies on the rate of release of cell associated antibiotic and of the effects of surface active agents indicated that the differences between cell types were due to loss of cell association during washing procedures to remove extracellular antibiotic. The effects of bactericidal antibiotics on survival of bacteria phagocytosed by mouse macrophages suggested that the cell association observed in tissue culture cells represented true intracellular penetration rather than mere binding to the cell surface. Within families of antibiotics, alterations to the molecule change cell penetration and the variations observed can not be explained merely in terms of simple diffusion, molecular size, dissociation constants, lipid solubility or protein binding.

Animals↗
PubMed1985

Interconversion of tight and loose couple 50 S ribosomes and translocation in protein synthesis.

On incubation of 50 S ribosomes, isolated from either tight couple (TC) or loose couple (LC) 70 S ribosomes, with elongation factor G (EG-G) and guanosine 5'-triphosphate, a mixture of TC and LC 50 S ribosomes is formed. There is almost complete conversion of LC 50 S ribosomes to TC 50 S ribosomes on treatment with EF-G, GTP, and fusidic acid. Similarly, TC 50 S ribosomes are converted to LC 50 S ribosomes, although partially, by treatment with EF-G and a GTP analogue like guanyl-5'-yl methylenediphosphate (GMP-P(CH2)P) or guanyl-5'-yl imidodiphosphate (GMP-P(NH)P) and including a polymer of 5'-uridylic acid (poly(U] in the incubation mixture. Furthermore, LC 23 S RNA isolated from LC 50 S ribosomes is converted to TC 23 S RNA on heat treatment, but similar treatment does not affect TC 23 S RNA. The interconversion was followed by several physical and biological characteristics of TC and LC 50 S ribosomes, like association capacities with 30 S ribosomes before and after kethoxal treatment, susceptibility to RNase I and polyphenylalanine-synthesizing capacity in association with 30 S ribosomes, as well as thermal denaturation profiles, circular dichroic spectra, and association capacity of isolated 23 S RNAs. These data strongly support the proposition that TC and LC 50 S ribosomes are the products of translocation during protein synthesis. The conformational change of 23 S RNA induced by EF-G and GTP is most probably responsible for the interconversion, and L7/L12 proteins play an important role in the process. A two-site model based on kethoxal data has also been proposed to explain the tightness and looseness of 70 S couples.

Cell Fractionation↗
PubMed1984

Antimicrobial susceptibility of anaerobic bacteria in Sweden in 1983.

This review is concerned with anaerobic bacteria and antimicrobial susceptibility. Data on the susceptibility to different antimicrobials of anaerobic isolates in Sweden during 1983 is presented. Among the different bacterial groups, Clostridium perfringens, propionibacteria, anaerobic cocci and curved rods were found to be susceptible to beta-lactam antibiotics, clindamycin and chloramphenicol. C. difficile was susceptible to benzylpenicillin and imipenem, but resistant to cefoxitin. Most C. difficile strains were also susceptible to clindamycin and fusidic acid, while all strains were susceptible to metronidazole and vancomycin. The majority of the fusobacteria were susceptible to beta-lactam antibiotics, clindamycin, metronidazole and chloramphenicol. However, some strains were found to be resistant to penicillins. Against the Bacteroides fragilis group, clindamycin, chloramphenicol, metronidazole and imipenem had the best activity, whereas piperacillin and cefoxitin showed good activities. Most Bacteroides non-fragilis strains were susceptible to the antimicrobials tested. However, an increasing number of isolates were found to be resistant especially to penicillins when comparing with data from the last five years.

Anti-Bacterial Agents↗
PubMed1983

Ribosomal protein L1 from Escherichia coli. Its role in the binding of tRNA to the ribosome and in elongation factor g-dependent gtp hydrolysis.

Two Escherichia coli mutants lacking ribosomal protein L1, previously shown to display 40 to 60% reduced capacity for in vitro protein synthesis (Subramanian, A. R., and Dabbs, E. R. (1980) Eur. J. Biochem. 112, 425-430), have been used to study partial reactions of protein biosynthesis. Both the binding of N-acetyl-Phe-tRNA to ribosomes and the 6 to 8-fold stimulation of the elongation factor G (EF-G)-dependent GTPase reaction by mRNA plus tRNA, assayed in the presence of wild type 30 S subunits, were low with L1-deficient 50 S subunits. Addition of pure protein L1 to the assay restored both reactions to 100% of the control. By contrast, the basic EF-G GTPase reaction in the absence of mRNA and tRNA was not at all affected (mRNA alone had no effect). None of the following partial reactions were more than moderately modified by the lack of protein L1: binding to ribosomes of EF-G.GDP plus fusidic acid; the translocation reaction catalyzed by EF-G plus GTP; poly(U)-dependent binding to ribosomes of Phe-tRNAPhe (whether dependent on elongation factor Tu plus GTP or not); and the EF-Tu-dependent GTPase activity. It is concluded that protein L1 is involved in the interaction between ribosomes and peptidyl-tRNA (or tRNA) in the peptidyl site and consequently in the ribosomal GTPase activity depending on the simultaneous action of tRNA and EF-G.

Bacterial Proteins↗