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We describe a 46-year-old man who developed infective endocarditis, meningitis, sternal abscess, and infective cerebral emboli after cardiac transplantation. Staphylococcus aureus was the infective organism. We successfully managed the patient with flucloxacillin and fusidic acid to treat infection, and with prostacyclin for systemic embolization.
Five hundred strains of methicillin-resistant Staphylococcus aureus were tested against various anti-staphylococcal agents. Vancomycin, fusidic acid and fosfomycin were found to be the most effective. Only 1 strain out of 500 was resistant to fosfomycin. Three patients with methicillin-resistant Staphylococcus aureus septicaemia were successfully treated by fosfomycin. We conclude that fosfomycin could be the drug of choice for methicillin-resistant Staphylococcus aureus infection.
The spontaneous dissociation of complexes containing elongation factor G (EF-G), the ribosome, and either GDP plus fusidic acid, guanyl-5'-yl imidodiphosphate, or guanyl-5'-yl methylene diphosphonate has been measured and it follows biphasic kinetics that can be resolved into two first-order decay rates. This suggest the existence of two classes of complexes with apparent dissociation rate constants (k) differing 5--20-fold. The values of k and the distribution of complexes between the fast and the slowly decaying class depend on the conditions in which the dissociation occurs but not on the conditions in which the complexes are formed. Rapid transitions of complexes from one to the other class occur only when the chemical environment in which the dissociation takes place is modified. Thus, increasing the concentration of NH4Cl or adding the antibiotic thiostrepton accelerates the decay and converts slowly dissociating into fast dissociating complexes. In contrast, addition of misreading-inducing aminoglycoside antibiotics of the neomycin, kanamycin, streptomycin, and gentamicin (but not hygromycin) groups slows down the decay. For neomycin B at 10 micron, this effect is due to the conversion of fast into slowly decaying complexes. A model to explain the results involving conformational transitions of the complexes is proposed.
Over a period of three years the incidence of methicillin resistant Staphylococcus aureus (MRSA) isolates in 11 hospitals in the greater Düsseldorf area was observed. From a total of 7,814 S. aureus isolates, 489 (6.3%) were methicillin resistant. From 198 different patients, MRSA first isolates and 291 second isolates could be cultured. Methicillin resistance among all S. aureus isolates from 11 hospitals in the greater Düsseldorf area, ranged from 0.5 to 7.8% dependant on the size of the hospital. The highest incidence (7.8%) was found in a 1,500 bed hospital and the lowest incidence in a smaller 200 bed hospital (0.5%). With respect to the distribution among clinical departments the highest incidence of MRSA isolates was found on intensive care units and surgical wards, 25.5% and 13.0% respectively. The commonest specimen from which the MRSA isolates were cultured were respiratory secretions (17.6%) followed by central venous catheter tips (12.8%). In terms of the drug resistance pattern: all isolates were resistant to the aminoglycosides and gyrase inhibitors, whereas between 80% and 90% were sensitive to fusidic acid, chloramphenicol and pyrimethamine-sulfamethoxazole. All the strains were sensitive to the glycopeptide antibiotics, vancomycin and teicoplanin. Strain typing of 181 available first isolates (from a total of 198 first isolates) by PFGE and phage lysotyping produced identical results in more than 90% of all cases. Twenty-eight different MRSA strain types were identified by PFGE and in total 23 lysotypes could be determined. During the period of investigation an increased incidence of MRSA on an intensive care unit was observed, in which a total of 204 MRSA (42% of the total number) were isolated. The strain typing using both methods showed that on that ICU eight different MRSA types were involved in this outbreak. A hygiene plan was implemented on the unit with considerable success in reducing the incidence and spread of MRSA.
The bile salt derivative sodium tauro-24,25-dihydrofusidate (STDHF) has been reported to promote nasal absorption of insulin. In the present study the effect of STDHF on rectal insulin absorption was investigated in rats. At concentrations of 1 and 4% (w/v) it enhanced insulin bioavailability from 0.2 +/- 0.2 (control) to 4.2 +/- 3.2 and 6.7 +/- 2.1%, respectively, as assessed by radioimmunoassay. Insulin preparations with STDHF reduced blood glucose concentrations considerably in a concentration-dependent way. Coadministration of STDHF with Na2EDTA (0.25%, w/v) tended to increase further insulin bioavailability and hypoglycemic response. Varying the site of rectal administration did not influence these parameters.
Homogenates of rat kidney cortex obtained 1,3 or 14 days after a single injection of HgCl2 were used to prepare the post-microsomal pH5 supernatant fraction. The activity of this fraction for peptide synthesis from [14C]phenylalanyl-tRNA was significantly increased at 1 and 3 days, at which time the proximal tubules are regenerating [Cuppage & Tate (1967) Am. J. Pathol. 51, 405-429]. This increased activity could not be attributed to a decreased inhibitory activity, but was due to an increased aminoacyl-tRNA binding, i.e. elongation-factor-1 activity, in the supernatant fraction.
Purpuromycin, an antibiotic isolated from the culture broth of Actinoplanes ianthinogenes, which is very active against Gram-positive bacteria and fungi, inhibits protein synthesis in both prokaryotic and eukaryotic cell-free systems. The ID50 was 9 microM with the endogenous mRNA-directed rabbit reticulocyte lysate, 17 microM with a poly(U)-directed system from Escherichia coli and 69 microM with a poly(U)-directed system from Artemia salina cysts. Of the three steps of elongation, purpuromycin does not affect the peptidyl-transferase reaction, inhibits the elongation factor 1 (EF-1) dependent binding of phenylalanyl-tRNA and stimulates the GTP-dependent binding of EF-2. When protein synthesis is stopped by the addition of purpuromycin, the nascent peptide chains are found in the puromycin-reactive P site. The results suggest that the mechanism of action of purpuromycin is similar to that of fusidic acid. Both antibiotics would seem to produce a stable guanine nucleotide-ribosome-EF-2 complex which allows one round of translocation but prevents, because of a common or overlapping ribosomal binding site for the two elongation factors, the subsequent EF-1-dependent binding of aminoacyl-tRNA.
Skin colonization with Staphylococcus aureus is a characteristic feature of atopic dermatitis with more than 90% of patients being colonized. Extracellular matrix proteins are important for the adherence of S. aureus to human keratinocytes. The bacterium interferes in the inflammatory process of atopic dermatitis in various ways, among which the ability to release superantigens in a high percentage of clinical isolates is of great importance. As the colonization correlates significantly with the severity of eczema, anti-staphylococcal treatment measurements are widely used. In cases of atopic dermatitis exacerbation with wide-spread weeping lesions, a systemic antibiotic treatment is warranted, with erythromycin no longer being recommended due to an increased resistance rate. In localized superinfected lesions the topical application of an antibiotic-glucocorticoid preparation may offer advantages to the mere steroid application. Based on efficacy and resistance data, fusidic acid is the antibiotic of choice. There is evidence that phototherapy in atopic dermatitis may be even more effective when combined with anti-staphylococcal measurements. In the future new therapeutical options may be available.
BACKGROUND: Propionibacterium acnes is the target of antimicrobial treatments for acne vulgaris. Acquired resistance to erythromycin, clindamycin and tetracyclines has been reported in strains from diverse geographical loci, but the molecular basis of resistance, via mutations in genes encoding 23S and 16S rRNA, respectively, has so far only been elucidated for isolates from the U.K. OBJECTIVES: To determine whether similar or different resistance mechanisms occur in resistant P. acnes isolates from outside the U.K. METHODS: The phenotypes and genotypes of 73 antibiotic-resistant strains of P. acnes obtained from the skin of acne patients in the U.K., U.S.A., France, Germany, Australia and Japan were compared. Antibiotic susceptibilities were determined by minimum inhibitory concentration (MIC) measurements, and polymerase chain reaction and DNA sequencing were used to identify mutations in genes encoding rRNA. RESULTS: Most erythromycin-resistant isolates (MIC(90) > or = 512 microg mL(-1)) were cross-resistant to clindamycin but at a much lower level (MIC(90) > or = 64 microg mL(-1)). As in the U.K., resistance to erythromycin was associated with point mutations in 23S rRNA in 49 of 58 strains. An A-->G transition at Escherichia coli equivalent base 2058 was present in 24 strains. This gave a unique cross-resistance phenotype against a panel of macrolide, lincosamide and type B streptogramin antibiotics. Two further point mutations (at E. coli equivalent bases 2057 and 2059) were identified (in three and 22 isolates, respectively) and these were also associated with specific cross-resistance patterns originally identified in isolates from the U.K. However, nine of 10 erythromycin resistant-strains from Germany did not exhibit any of the three base mutations identified and, in six cases, cross-resistance patterns were atypical. Consistent with previous U.K. data, 34 of 38 tetracycline-resistant strains carried a base mutation at E. coli 16S rRNA equivalent base 1058. Tetracycline-resistant isolates displayed varying degrees of cross-resistance to doxycycline and minocycline, but isolates from the U.S.A. had higher MICs for minocycline (4--16 microg mL(-1)) than isolates from other countries and, in particular, Australia. All the P. acnes isolates resistant to one or more of the commonly used antiacne antibiotics were sensitive to penicillin, fusidic acid, chloramphenicol and the fluoroquinolone, nadifloxacin. All but one isolate (from the U.K.) were sensitive to trimethoprim. CONCLUSIONS: This study shows that 23S and 16S mutations identified in the U.K. conferring antibiotic resistance in P. acnes are distributed widely. However, resistant strains were isolated in which mutations could not be identified, suggesting that as yet uncharacterized resistance mechanisms have evolved. This is the first report of high-level resistance to minocycline and is of concern as these strains are predicted to be clinically resistant and are unlikely to remain confined to the U.S.A. Epidemiological studies are urgently required to monitor how resistant strains are selected, how they spread and to ascertain whether the prevalence of resistance correlates with antibiotic usage patterns in the different countries.
BACKGROUND: All centres use an empirically determined set of 'standard' test allergens for patch testing that contain the commoner environmental sensitizers. Objectives To assess the validity of the British standard series of 12 allergens used in addition to the 23 already in the European standard series. PATIENTS AND METHODS: Results for 3062 consecutive patients patch tested in seven centres across the United Kingdom during the year 2000 were analysed. RESULTS: The additional allergens from the British series and positive rates were: methyl dibromoglutaronitrile 2.4%, carba mix 1.6%, tixocortol pivalate 1.5%, ethylenediamine 1.3%, cetearyl alcohol 0.8%, 2-bromo-2-nitropane-1,3-diol 0.8%, diazolidinyl urea 0.7%, chlorocresol 0.6%, budesonide 0.6%, fusidic acid 0.5%, imidazolidinyl urea 0.5%, and chloroxylenol 0.4%. The allergens with the lowest positive rate in the European standard series were primin at 0.6% and isopropyl-phenyl-para-phenylenediamine at 0.4%. CONCLUSIONS: The 12 allergens in the British series should continue being tested as a standard addition to the European series within the U.K. The collection of data in this manner to allow comparisons between centres shows differences that reflect selection criteria and interpretation of results, and offers a useful tool for audit and clinical governance. Testing fewer than 1 : 2150 population may indicate underprovision of service. Similarly, rates of sensitization for nickel contact allergy above 26% and for fragrance mix above 16% (the upper 95% confidence intervals) should stimulate inquiry into the reasons behind this.
BACKGROUND: The incidence of strains of Staphylococcus aureus resistant to the antimicrobial agents used in treating impetigo has been increasing. AIM: To determine the antimicrobial susceptibility of S. aureus in impetigo. METHODS: We measured the antimicrobial susceptibility of Staphylococcus aureus isolated from impetigo patients between 1994 and 2000. RESULTS: The MIC50 of gentamicin was always higher than that of other antimicrobial agents until 1999. In isolates obtained since 1996, the MIC90 of gentamicin was over 12.5 micro g/mL, which is markedly higher than that found for other skin infections (folliculitis, furuncles, paronychia, phlegmone, secondary infection of eczema, dermatitis, ulcer and decubitus). There were no strains of S. aureus resistant to vancomycin and fusidic acid. After 2000, we could find only one strain resistant to minocycline and ofloxacin. CONCLUSION: Clindamycin has shown excellent activity against most S. aureus isolates between 1994 and 2000. The incidence of methicillin-resistant S. aureus was always below 20%.
OBJECTIVE: To investigate the natural susceptibility to 69 antimicrobial agents of 107 Enterobacter strains comprising E. amnigenus (n = 18), E. cancerogenus (n = 26), E. gergoviae (n = 28) and E. sakazakii (n = 35). METHODS: Minimal inhibitory concentrations (MICs) were determined with a microdilution procedure in Isosensitest broth and cation-adjusted Mueller-Hinton broth. RESULTS: All the species were naturally sensitive or intermediate to tetracyclines, amino-glycosides, numerous beta-lactams (acylureidopenicillins, ticarcillin, ampicillin/sulbactam, several cephalosporins, carbapenems, aztreonam), quinolones, antifolates, chloramphenicol and nitrofurantoin. Natural resistance was found to penicillin G, oxacillin, several macrolides, lincosamides, streptogramins, glycopeptides, rifampicin and fusidic acid. Species-related differences in natural susceptibility were found to some beta-lactams, azithromycin and fosfomycin. Whereas E. gergoviae was the most susceptible species to azithromycin, E. cancerogenus was most susceptible to fosfomycin and was the only species showing natural resistance to amoxicillin, amoxicillin/clavulanic acid, cefaclor, cefazoline, loracarbef and cefoxitin. There were only minor medium-dependent differences in susceptibility to most antibiotics. CONCLUSIONS: The present study establishes a database concerning the natural susceptibility of recently established Enterobacter species to a wide range of antibiotics, which can be applied for the validation of routine susceptibility test results. beta-Lactam susceptibility patterns indicate the expression of species-specific beta-lactamases expressed at high or low levels in all the species except E. sakazakii.
Sixteen Bifidobacterium isolates from the human gastrointestinal tract were assayed for susceptibility to 44 antibiotics by soft agar overlay disc diffusion on TPY agar. Five isolates (3/7 B. bifidum and 2/3 B. breve) exhibited atypical antibiotic susceptibility profiles. Poor growth in the agar overlay accounted for susceptibility of B. bifidum but not B. breve isolates. All other isolates were resistant to cefoxitin (30 micrograms), aztreonam (30 micrograms), vancomycin (30 micrograms), amikacin (30 micrograms), gentamicin (10 micrograms), kanamycin (30 micrograms), streptomycin (10 micrograms), fusidic acid (10 micrograms), trimethoprim (5 micrograms), norfloxacin (10 micrograms), nalidixic acid (30 micrograms), metronidazole (5 micrograms), polymyxin B (300 micrograms) and colistin sulphate (10 micrograms), and they were susceptible to the six penicillins studied, cephalothin (30 micrograms), cefuroxime (30 micrograms), cefaclor (30 micrograms), ceftizoxime (30 micrograms), cefotaxime (30 micrograms), bacitracin (10 micrograms), chloramphenicol (30 micrograms), erythromycin (15 micrograms), clindamycin (2 micrograms), rifampicin (5 micrograms) and nitrofurantoin (300 micrograms). In addition, they varied in their susceptibility to cephradine (30 micrograms), cephazolin (30 micrograms), cefoperazone (75 micrograms), ceftriaxone (30 micrograms), ofloxacin (5 micrograms) and furazolidone (15 micrograms). They were resistant, or only marginally moderately susceptible, to ceftazidime (30 micrograms), netilmicin (10 micrograms), sulphamethoxazole (100 micrograms), cotrimoxazole (25 micrograms) and ciprofloxacin (5 micrograms), and susceptible or marginally moderately susceptible to tetracycline (30 micrograms). All B. bifidum isolates were susceptible to cefixime (5 micrograms). Four microorganism-drug combinations were evaluated for beta-lactamase activity but its absence suggested that cell wall impermeability was responsible for cephalosporin resistance among bifidobacteria. The antibiotic susceptibility of B. animalis 25527T was similar to that of the human isolates.
Two patient histories show that the therapy of contact lens corneal ulcers is complicated by bacterial resistance and mixed infection. To start an effective therapy against pseudomonas, gram-negative as well as gram-positive germs, a primary combination of tobramycin with fusidic acid seems to us as reasonable. Because of possible resistance to these antibiotics a smear should be taken from the ulcer and the contact lens case before therapy is begun and the clinical evolution must be controlled. In the choice of the antibiotics, the actual state of resistance and commercial availability was taken into account.
HISTORY AND FINDINGS: In a 32-year-old 26-week pregnant woman with atopic eczema densely packed blisters, ca. 1 mm in diameter, developed within the eczema areas, typical of herpetic eczema. This diagnosis was confirmed by identifying the virus under the electronmicroscope and demonstrating herpes simplex virus DNA in the polymerase chain reaction. TREATMENT AND COURSE: During intravenous aciclovir administration (5 mg/kg three times daily for 9 days) the blisters quickly healed. As a bacterial superinfection was suspected (later confirmed by culturing Staphylococcus aureus from a skin swab) the patient was also given erythromycin (500 mg four times daily by mouth for 7 days), as well as fusidic acid cream locally. She delivered a healthy child in the 37th week of pregnancy. CONCLUSION: Herpetic eczema is a serious complication of chronic eczema. If it occurs during pregnancy, the risk or fetal damage by aciclovir must be balanced against the risk of intrauterine herpes simplex infection.
Confluent and reticulated papillomatosis (CRP) is a relatively rare disorder manifested by persistent papules that are confluent in the center and reticulated at the periphery with a characteristic distribution. Recently, many cases of CRP treated with minocycline have been reported, and their effect seems to be derived from their antibiotic properties. We report 6 cases of CRP alleviated by various antibiotics. The patient described in case 1 is a 16-year-old girl whose disease was alleviated by oral minocycline, 100 mg daily for 8 weeks. Cases 2 and 3 describe an 18-year-old woman and a 17-year-old male adolescent whose disease was reduced by oral fusidic acid, 1000 mg daily for 4 weeks. Case 4 describes a 14-year-old girl who received oral clarithromycin, 500 mg daily for 5 weeks. Case 5 describes a 22-year-old woman whose disease was reduced by oral erythromycin, 1000 mg daily for 6 weeks. Case 5 reports a 24-year-old man who received oral azithromycin, 500 mg daily 3 times per week for 3 weeks. Complete clearing after treatment with antibiotics raises the possibility that CRP is triggered by a bacterial infection and that antibiotics are the treatment of choice for CRP.
Staphylococcus aureus is an important nosocomial and community-acquired pathogen. Its genetic plasticity has facilitated the evolution of many virulent and drug-resistant strains, presenting a major and constantly changing clinical challenge. We sequenced the approximately 2.8-Mbp genomes of two disease-causing S. aureus strains isolated from distinct clinical settings: a recent hospital-acquired representative of the epidemic methicillin-resistant S. aureus EMRSA-16 clone (MRSA252), a clinically important and globally prevalent lineage; and a representative of an invasive community-acquired methicillin-susceptible S. aureus clone (MSSA476). A comparative-genomics approach was used to explore the mechanisms of evolution of clinically important S. aureus genomes and to identify regions affecting virulence and drug resistance. The genome sequences of MRSA252 and MSSA476 have a well conserved core region but differ markedly in their accessory genetic elements. MRSA252 is the most genetically diverse S. aureus strain sequenced to date: approximately 6% of the genome is novel compared with other published genomes, and it contains several unique genetic elements. MSSA476 is methicillin-susceptible, but it contains a novel Staphylococcal chromosomal cassette (SCC) mec-like element (designated SCC(476)), which is integrated at the same site on the chromosome as SCCmec elements in MRSA strains but encodes a putative fusidic acid resistance protein. The crucial role that accessory elements play in the rapid evolution of S. aureus is clearly illustrated by comparing the MSSA476 genome with that of an extremely closely related MRSA community-acquired strain; the differential distribution of large mobile elements carrying virulence and drug-resistance determinants may be responsible for the clinically important phenotypic differences in these strains.
A new RNase activity, tentatively named RNase V, was found in cell-free extracts of E. coli. This activity requires ribosomes, G and T factors, tRNA, K(+) or NH(4) (+), Mg(2+), GTP, and a sulfhydryl compound to degrade poly U, poly A, T4 phage mRNA, or E. coli mRNA. RNase V is specific for mRNA; it does not attack ribosomal RNA. It is inhibited by antibiotics that decrease breakdown of mRNA in vivo, such as chloramphenicol and streptomycin, and by such agents as 5'-beta, gamma-methylene-guanosine triphosphate, and fusidic acid, which inhibit ribosome-dependent GTPase and translocation of ribosomes along mRNA. The evidence suggests that RNase V is either an integral part of the ribosome or is tightly associated with it, and that it selectively degrades mRNA in intact cells.