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Fifty-four clinical isolates of Nocardia spp. were tested in vitro for susceptibility to several antimicrobial agents. Of these, 89% were susceptible to ciprofloxacin, 86% to imipenem, 85% to fusidic acid, and 71% to cefotaxime. Some of the agents may be suitable alternative or adjunctive drugs to sulfonamides and aminoglycosides for chemotherapy of Nocardial infections.
BACKGROUND: Multiple antibiotic-resistant strains of Shigella dysenteriae type 1 were isolated from an epidemic in West Bengal, India (1984). During the past two decades, much attention was given to reevaluation of treatment recommendations. However, there are no useful data on drug resistance encoded by chromosome. METHODS: A total of 300 strains of Shigella dysenteriae type 1 were isolated from an epidemic. Strains were biochemically identified by API 20E system and further confirmed serologically. Antibiotic susceptibility was determined by disk diffusion method and plasmid DNA was prepared by alkaline lysis procedure. Elimination of plasmids was achieved by curing with acridine orange from a representative epidemic strain S. dysenteriae 1 Dt66. PFGE was performed for typing of wild-type and plasmid-cured strains. Southern blot of PFGE separated XbaI digested chromosomal DNA was done onto positively charged nylon membrane. For Southern hybridization, plasmid DNA was used as probe. RESULTS: All isolates showed identical drug resistance patterns and plasmid profiles. All these isolates contained six plasmids ranging in sizes from 3 to 145 kb. We have eliminated all the plasmids from a representative strain of S. dysenteriae 1 Dt66 by using acridine orange as curing agent. All epidemic Shigella isolates were resistant to amoxycillin, ampicillin, bacitracin, carbenicillin, cefixime, ceftazidime, chloramphenicol, clarithromycin, erythromycin, fusidic acid, methicillin, penicillin G, polymixin B, streptomycin, rifampicin, tetracycline and vancomycin, among 29 antibiotics used. Out of 17 resistant antibiotics, 12 were encoded by chromosome. Resistance to ampicillin, chloramphenicol, streptomycin, tetracycline and ceftazidime was plasmid encoded. Southern blot hybridization showed the recognition of two clear sites in the chromosome used plasmid DNA of Dt66 strain as probe, which reveled some sequential genetic homology between chromosome and plasmids. Pulsed-field gel electrophoresis (PFGE) was performed for typing of the chromosome of plasmidless strains of Dt66 and wild-type strain Dt66 (having plasmids) that remain unaltered. CONCLUSIONS: Seventy percent drug-resistant loci of Shigella dysenteriae 1 Dt66 are present in chromosome and the remaining are plasmid mediated.
Yokenella regensburgei is an opportunistic human pathogen that phenotypically resembles Hafnia alvei. The susceptibility of 10 Y. regensburgei strains to 75 antimicrobial agents was examined, applying a microdilution procedure in cation-adjusted Mueller-Hinton broth (CAMHB) and IsoSensitest broth (ISB). beta-Lactamases were characterized phenotypically with beta-lactamase activity and induction assays. Genotypically, PCR experiments applying degenerated primer pairs for the detection of AmpC beta-lactamase genes were performed. Examining the phenotypic properties of Yokenella and 76 H. alvei strains with commercial identification systems and conventional tests, a database for an accurate biochemical separation of Y. regensburgei from H. alvei was established. In CAMHB, all tested yokenellae were resistant or at least of intermediate susceptibility to penicillin G, oxacillin, amoxicillin, amoxicillin-clavulanate, cefaclor, cefazoline, loracarbef, cefoxitin, all tested macrolides, lincosamides, streptogramins, ketolides, fusidic acid, glycopeptides, linezolid, and rifampicin. All Yokenella strains were sensitive to several beta-lactams, all tested aminoglycosides, chloramphenicol, folate-pathway inhibitors, fosfomycin, nitrofurantion, quinolones, and tetracyclines. In ISB, the minimum inhibitory concentration (MIC) values of several beta-lactams were one to four MIC doubling dilution steps lower than those found in CAMHB (depending on the beta-lactam). All yokenellae yielded specific amplification products for ampC, and all of these strains expressed beta-lactamases that were strongly inducible. Hydroxyproline amidase, maltosidase, tri-peptidase, proline deaminase, catalase reaction, Voges-Proskauer test, and fermentation of glycerol, melibiose and myo-inositol were suitable parameters to separate Y. regensburgei from H. alvei.
Bangladeshi diarrheagenic Hafnia alvei-like strains have been described recently as the new species Escherichia albertii (Int J Syst Evolut Microbiol. 2003;53:807-810). The natural susceptibility of 21 E. albertii and 76 H. alvei strains to 69 antimicrobial agents was examined, applying a microdilution procedure in IsoSensitest broth (for all the strains) and cation-adjusted Mueller-Hinton broth (for some strains). Examining the phenotypic features of both taxa with commercial identification systems and conventional tests, a database for an accurate biochemical separation of E. albertii from H. alvei was also established. Both taxa were naturally sensitive or sensitive and of intermediate susceptibility to aminoglycosides, acylureidopenicillins, ticarcillin, several cephalosporins, carbapenems, aztreonam, quinolones, folate pathway inhibitors, and nitrofurantoin. They were naturally resistant to tetracycline, penicillin G, oxacillin, all macrolides except for azithromycin, lincosamides, streptogramins, glycopeptides, rifampicin, and fusidic acid. Taxon-related differences in natural susceptibility affecting clinical assessment criteria were seen with doxycycline, minocycline, aminopenicillins, some cephalosporins, azithromycin, and fosfomycin. E. albertii was more susceptible than H. alvei to these agents and was naturally sensitive to all beta-lactams (except for penicillin G and oxacillin), azithromycin, and fosfomycin. H. alvei was naturally resistant or of intermediate susceptibility to all tetracyclines, amoxicillin, amoxicillin-clavulanate, ampicillin-sulbactam, narrow-spectrum cephalosporins, azithromycin, and fosfomycin. Motile malonate-negative Hafnia strains (indicating genospecies 2 of the H. alvei complex) were less susceptible to some cephalosporins than nonmotile, malonate-positive hafniae (indicating genospecies 1). Proline deaminase, hydroxyproline amidase, tripeptidase, chitinase, Voges-Proskauer reaction, and assimilation of histidine as well as acid production from glycerol, rhamnose, and xylose were suitable tests to separate strains of E. albertii from those of the H. alvei complex. Although out of the scope of this study, it should be noted that several strains of E. albertii showed acquired resistances to some penicillins and antifolates.
All medically useful antibiotics should have the potential to distinguish between target microbes (bacteria) and host cells. Although many antibiotics that target bacterial protein synthesis show little effect on the translation machinery of the eukaryotic cytoplasm, it is unclear whether these antibiotics target or not the mitochondrial translation machinery. We employed an in vitro translation system from bovine mitochondria, which consists of mitochondrial ribosomes and mitochondrial elongation factors, to estimate the effect of antibiotics on mitichondrial protein synthesis. Tetracycline and thiostrepton showed similar inhibitory effects on both Escherichia coli and mitochondrial protein synthesis. The mitochondrial system was more resistant to tiamulin, macrolides, virginiamycin, fusidic acid and kirromycin than the E. coli system. The present results, taken together with atomic structure of the ribosome, may provide useful information for the rational design of new antibiotics having less adverse effects in humans and animals.
The sarA locus of Staphylococccus aureus regulates the synthesis of over 100 genes on the S. aureus chromosome. We now report the effects of sarA inactivation on intrinsic multidrug resistance expression by S. aureus. In a strain-dependent fashion, sarA::kan mutants of three unrelated strains of S. aureus demonstrated significantly increased susceptibility to five or more of the following substances: the antibiotics ciprofloxacin, fusidic acid, and vancomycin; the DNA-intercalating agent ethidium; and four common household cleaner formulations. In addition, all three sarA::kan mutants demonstrated significantly increased accumulation of ciprofloxacin and one sarA::kan mutant demonstrated increased ethidium accumulation. Our data therefore indicate that sarA plays a role in the intrinsic multidrug resistance mechanism expressed by S. aureus, in part by regulating drug accumulation.
Non-aureus staphylococci and mammaliicocci (NASM) cause mastitis and may contaminate milk and dairy products. Milk samples (n = 1916) from cows with subclinical or clinical mastitis (SCM and CM, respectively) were collected from 28 large-scale (> 500 lactating cows) Chinese dairy farms. Overall, 999 NASM isolates representing 19 species were identified by MALDI-TOF MS and cpn60 sequencing, with Staphylococcuschromogenes, Mammaliicoccus sciuri and Staphylococcus haemolyticus being most prevalent. Antimicrobial resistance (AMR) was determined with disc diffusion; non-susceptible to penicillin was most common (SCM, 30% and CM, 29%) whereas cefoxitin non-susceptible NASM accounted for 8-10% of isolates; among these, 12.5% carried mecA but none carried mecC. Galleria mellonella was used to assess virulence of 78 strains of S. chromogenes, a dominant species; subsequently, 32 strains, representing higher- and lower-virulence in the Galleria model, were selected for whole-genome sequencing and comparative genomics. S. chromogenes isolates from CM had higher virulence (p < 0.05) than those from SCM. The 32 genomes comprised 20 sequence types, indicating high genetic diversity. No robust genomic marker of Galleria virulence phenotype was identified in this selected WGS subset. Acquired resistance genes (n = 5) were detected, including a first report of fusC in S. chromogenes; the fusC-positive isolate had an elevated fusidic acid MIC (8 mg/L). Although S. chromogenes persisted in milk at 4 °C, pasteurization (64 °C for 30 min) reduced viable counts to below detection. This study provided new insights into the prevalence, AMR, genomic diversity, and dairy-chain relevance of milk-derived NASM, particularly S. chromogenes. However, the genomic findings were based on an intentionally selected WGS subset and should be interpreted as hypothesis-generating rather than population-representative.
This study compares in vitro antimicrobial resistance development between strains of Staphylococcus aureus including newly described community-acquired methicillin-resistant strains (CA-MRSA). High-level resistance developed in all strains of S. aureus after exposure to rifampicin and gentamicin and in some strains after fusidic acid exposure, independent of methicillin resistance phenotype. Resistance did not develop after exposure to clindamycin, cotrimoxazole, ciprofloxacin, linezolid, or vancomycin. These results have important implications for therapy of CA-MRSA infections.
The susceptibility to 30 antimicrobial agents was determined by the disk diffusion method for a collection of 172 enterococcal strains, including 96 isolates from dairy sources, 50 isolates of human and veterinary origin, and 26 reference strains from 24 different enterococcal species. Results were analysed by hierarchic numerical methods to cluster strains and to group antimicrobials according to similarity profiles. Resistance to 17 of the 30 antimicrobials showed to be correlated, leading to four groups reflecting the mode of action: quinolones (ofloxacin, enrofloxacin, ciprofloxacin and norfloxacin); macrolides (erythromycin, spiramycin), phenicols (cloramphenicol) and tetracyclins (tetracycline, oxytetracyclin); aminoglycosides (gentamicin, kanamycin) and lincosamides (clindamycin); penicillins (amoxicillin, ampicillin, penicillin G, piperacillin) and carbapenems (imipenem). Overall, the genus Enterococcus behaved as resistant to lincomycin, colistin, polimixin B and, with a few exceptions in dairy isolates, to methicillin. In general, all isolates were susceptible to vancomycin, cloramphenicol and fusidic acid. Clusters containing only dairy isolates were susceptible to the majority of antimicrobials tested, as opposed to clusters constituted only by clinical enterococcal isolates. Among the clinical isolates, 62% were highly multiresistant. Low level gentamicin resistance was found to be associated with clinical enterococci. Among dairy isolates, those that clustered with clinical isolates were both resistant to gentamicin and identified as Enterococcus faecalis. Resistance to macrolides, quinolones, penicillins and imipenem was found to be associated also with clinical environments, mainly with multiresistant isolates, contrary to what is generally agreed as a characteristic of the genus. Veterinary clinical isolates were mainly grouped with the multiresistant clinical human isolates. The 26 reference enterococcal strains were distributed in clusters with different antibiotic resistance profiles and were mainly clustered with dairy isolates.
Methicillin-resistant Staphylococcus aureus (MRSA) susceptible strains to aminoglycosides (AS-MRSA) have been increasingly isolated in the Albert Cheneiver Hospital during the past 10 years. The aim of this study was first, to analyse the genotypes and the profiles of resistance to antibiotics and second to compare the AS-MRSA with the MRSA resistant to gentamicin (GR-MRSA) and with MRSA resistant to kanamycin and tobramycin, but susceptible to gentamicin (GS-MRSA), previously studied in our laboratory. All the AS-MRSA consecutively isolated from clinical samples (carriage isolates excluded) from 01/01/1993 to 31/12/2002 (33 isolates) were typed by DNA macrorestriction. Their susceptibilities to other anti-staphylococcal drugs (erythromycin, lincomycin, tetracycline, rifampicin, fusidic acid and fosfomycin) were studied by the French standard disk method. The 33 strains showed a heterogeneous resistance to oxacillin and fell into five phenotypes. The main phenotype (51.5% of the AS-MRSA strains) was susceptible to the six antibiotics studied. DNA macrorestriction defined 24 genotypes (percentage similarity <80%). Among them 16 genotypes contained only one strain each, and none contained more than three isolates. Conversely the comparison with GR-MRSA and GS-MRSA isolated during the same period showed that the strains were not closely linked. The diversity of our isolates showed that it was not an epidemic phenomenon, in contrast to the results of similar studies. Our findings may be explained by the patients coming mostly from different hospital units. This work indicates the need for further studies on the genome, to determine whether AS-MRSA have derived from strains that occurred before aminoglycosides came into clinical use.
A retrospective survey was conducted at Bicêtre Hospital, France from January 2001 to September 2003 to screen for S. aureus isolates with a typical phenotype previously involved in necrotizing pneumonia in France. They were resistant to oxacillin and kanamycin, of intermediate susceptibility to fusidic acid, and susceptible to tobramycin and fluoroquinolones. Seventeen isolates were found and 16 were viable. The Panton-Valentine leukocidin (PVL) genes, various toxin genes and SCCmec IV and agr3 alleles were detected in all isolates. The clonal origin of these isolates was demonstrated by pulsed-field gel electrophoresis. Fourteen isolates were community-acquired methicillin-resistant Staphylococcus (CA-MRSA) isolated from previously healthy patients with skin or soft tissue infections. Three infections were of nosocomial origin, underlining that these PVL-producing CA-MRSA strains may also be hospital acquired. Five CA-MRSA isolates with an identical resistance phenotype collected in a neighbouring teaching hospital (Hôpital Pitié-Salpétrière, Paris, France) were also PVL positive. Three isolates were clonally related to those of the Bicêtre Hospital whereas two were not. This retrospective study identified PVL-producing CA-MRSA in two Parisian hospitals. The incidence at Bicêtre Hospital was 0.8% of all S. aureus and 2% of all MRSA isolated. Our data indicate that these MRSA isolates might become hospital acquired.
OBJECTIVES: To determine the identity of European ocular bacterial pathogens and their susceptibility to topical antimicrobial agents. METHODS: Bacterial isolates derived from clinically significant ocular infections were collected from 10 European centres. Bacteria were re-identified and susceptibility to gatifloxacin, ciprofloxacin, ofloxacin, fusidic acid, gentamicin and chloramphenicol was determined using the NCCLS agar incorporation method at a central testing laboratory. RESULTS: Five hundred and thirty-two isolates were submitted for analysis. The most common pathogen was methicillin-susceptible Staphylococcus aureus, followed by Haemophilus influenzae and Streptococcus pneumoniae. Gatifloxacin was the most potent antimicrobial agent tested for isolates from each European country as measured by pure MIC or percentage resistance (using 95% confidence intervals). Only methicillin-resistant S. aureus was in any way refractory to the action of gatifloxacin and other fluoroquinolones. CONCLUSIONS: Fluoroquinolones offer broad-spectrum coverage for the treatment of ocular pathogens. Gatifloxacin ophthalmic solution should be a significant improvement on currently available fluoroquinolones mainly due to enhanced activity against streptococci and coagulase-negative staphylococci (which accounted for almost one-third of ocular pathogens).
OBJECTIVES: The purpose of this report was to describe epidemiological, clinical, and bacteriological findings in cases of Staphylococcus aureus bacteremia at the Infectious Diseases Clinic in Dakar. MATERIALS AND METHODS: This retrospective study was carried out on data recorded between January 1, 1996 and December 31, 2002. The diagnosis of bacteremia was based on isolation of bacteria from blood culture. Bacterial susceptibility was studied with an antibiogram. Resistance to methicillin was assessed with a disk containing 5 microg of oxacillin on Mueller Hinton Agar containing 5% of NaCl. RESULTS: One hundred and thirty cases of S. aureus bacteremia were recorded. The mean age of patients was 31 years. Nosocomial bacteremia occurred in 22% of the cases. HIV infection was noted in 38 patients (29%). The death rate was 24%. Nosocomial and community-acquired strains were resistant to methicillin, respectively, in 72% and 51% of the cases. Bacteremias due to methicillin-resistant S. aureus strain were nosocomial infections in 23% of the cases. Most of the strains (80-100%) were susceptible to fusidic acid, gentamycin, erythromycin, and pefloxacin. All of them were susceptible to vancomycin. CONCLUSION: Such a high rate of MRSA bacteremia, in particular among nosocomial bacteremia, makes it essential to reinforce preventive measures in our hospitals and to provide them with effective drugs against MRSA, such as vancomycin.
UNLABELLED: Resistance to antibiotics is a global problem in geriatric centres. OBJECTIVE: The aim of this study was to determine the frequency of the resistance to linezolid in Staphylococcus aureus strains before its release in a geriatric centre. METHOD: From 03-01-01 to 03-04-30 linezolid was included in the panel of antibiotics tested in S. aureus strains. The susceptibilities were estimated by the disk diffusion test in routine clinical microbiology practice. RESULTS: A total of 213 strains of S. aureus was analysed. All of them were susceptible to the following antibiotics: linezolid, cotrimoxazol, fosfomycin, and glycopeptides. The meticillin-resistant S. aureus (MRSA) represented 67.1% (60.3-73.3) strains. The resistance to pefloxacin, tobramycin and erythromycin concerned 92.3% (86.3-95.9), 73.4% (65.3-80.3) and 31.5% (24.1-39.8) of MRSA strains respectively. The MRSA strains were less resistant to the following antimicrobial drugs: gentamicin 7.0% (3.6-12.8), fusidic acid 2.1% (0.5-6.5) and rifampicin 1.4% (0.2-5.5). The resistance concerning at the same time gentamicin, pefloxacin and fucidic acid represented 2.1% (0.5-6.5) of SARM strains, rifampicin was not interested. CONCLUSION: Linezolid was effective in vitro in S. aureus strains regardless their susceptibilities in meticillin. According to its effectiveness in vivo, linezolid may be of use for the treatment of infections due to MRSA. However, there has been two reports of resistance of MRSA in clinical infections. The use of linezolid has to follow the instructions and it should be carefully monitored.
We looked for links between the antibiotic susceptibility pattern of Staphylococcus aureus strains, their source and their virulence genes. Forty-four methicillin-sensitive and -resistant S. aureus strains from four antibiogroups were studied by SmaI macrorestriction and PCR detection of ea, eb, tst, lukS-PV and lukF-PV. Genes encoding virulence factors were most prevalent (i) in S. aureus strains originated from skin, (ii) in methicillin-sensitive, quinolone-resistant strains or in methicillin-sensitive multiresistant strains (EMSSA strains), and (iii) in strains with decreased susceptibility or resistance to fusidic acid. This is consistent with the hypothesis that S. aureus antibiotic resistance promoted by local antibiotic treatment also contributes to the emergence of virulence strains.
The occurrence of antimicrobial-resistant Staphylococcus intermedius strains was investigated in 13 dogs affected by deep pyoderma, their owners and 13 individuals without daily contact with dogs (control group). A total of 90 canine and 33 human S. intermedius isolates were typed by pulsed field gel electrophoresis (PFGE) to determine their possible identity. The occurrence of S. intermedius in dog-owners was significantly higher compared with the control group (Fisher's exact test, P=0.03), with S. intermedius being detected in seven dog-owners and in one individual not exposed to dogs. The results of the PFGE analysis showed that six out of 13 (46%) owners carried strains identical to those isolated from their dogs. Strains detected in both dogs and humans were resistant up to five different antimicrobial classes, including penicillins, fusidic acid, macrolides/lincosamides, tetracycline and chloramphenicol. Based on the results of this study, owners of dogs affected by deep pyoderma often carry multiple antimicrobial-resistant strains of S. intermedius occurring in their dogs. Independent of the direction and modalities of transmission, this finding raises questions concerning the possible transfer of resistance genes from canine S. intermedius to human pathogenic staphylococci.
Bullous pemphigoid (BP) is a disease that characteristically affects the elderly, although cases have been described in children. We present a case of BP in a two-month-old infant with bullous lesions on the palms and soles, which appeared one week after receiving the first dose of the hepatitis B, polio, DTP and HiB vaccine. She was treated with sulphated water, dexamethasone and fusidic acid, and the lesions disappeared. One month later, she presented with a new, more generalized outbreak, three days after the second dose of the same vaccine. The skin eruption completely subsided 3 months after treatment with deflazacort was initiated (1 mg/kg/day). After five years of follow up, the patient has not presented with lesions again, despite having received the rest of the vaccines on the official schedule.
3alpha-Hydroxysteroid dehydrogenase/carbonyl reductase (3alpha-HSD/CR) catalyses the oxidoreduction at carbon 3 of steroid hormones and is postulated to initiate the complete mineralisation of the steroid nucleus to CO(2) and H(2)O in Comamonas testosteroni. The enzyme was found to be functional towards a variety of steroid substrates, including the steroid antibiotic fusidic acid. The enzyme also catalyses the carbonyl reduction of non-steroidal aldehydes and ketones such as a novel insecticide. It is suggested that 3alpha-HSD/CR contributes to important defense strategies of C. testosteroni against natural and synthetic toxicants. The 3alpha-HSD/CR gene (hsdA) is 774 base pairs long and the deduced amino acid sequence comprises 258 residues with a calculated molecular mass of 26.4 kDa. A homology search revealed 3alpha-HSD/CR as a new member of the short-chain dehydrogenase/reductase (SDR) superfamily. Upon gel permeation chromatography the purified enzyme elutes as a 49.4 kDa protein indicating a dimeric nature of 3alpha-HSD/CR. The protein was crystallised and the structure solved by X-ray analysis. The crystal structure reveals one homodimer per asymmetric unit, thereby verifying its dimeric nature. Dimerisation takes place via an interface essentially built-up by helix alphaG and strand betaG of each subunit. So far, this type of intermolecular contact has exclusively been observed in homotetrameric SDRs, but never in the structure of a homodimeric SDR. The formation of a tetramer is blocked in 3alpha-HSD/CR by the presence of a predominantly alpha-helical subdomain, which is missing in all other SDRs of known structure. The promoter domain was localised within the 93 bp region upstream of hsdA and the transcriptional start site was identified at 28 bp upstream of the translation start site. Interestingly, hsdA expression was found to be under negative control by two repressor proteins, the genes of which were found in opposite direction downstream or overlapping with hsdA. Based on our results, we propose that induction of hsdA expression in C. testosteroni by steroids actually appears to be a de-repression by preventing the binding of repressor proteins to regulatory regions.