Antimicrobial drug use and resistance among respiratory pathogens in the community.
(25/7957)
There is substantial evidence that the overuse of antibiotics is a major cause for the emergence of resistance in respiratory pathogens in the community. However, it is also recognized that the mechanisms of resistance, the cost of resistance to the fitness of the organism, and the ability of the resistant strain to disseminate are all important contributors to this problem. Therefore, when developing strategies to control and/or prevent the emergence of resistance, health care professionals must take each of these factors into consideration. As we enter a new era in the use of fluoroquinolones for the treatment of respiratory tract infections, we have an opportunity to apply such lessons learned in the past to minimize or prevent the development of resistance to this class of antimicrobial drugs in the future. (+info)
Does the dose matter?
(26/7957)
Pharmacokinetic/pharmacodynamic (PK/PD) parameters, such as the ratio of peak to minimum inhibitory concentration (peak/MIC ratio), ratio of 24-hour area under the curve to MIC (24-h AUC/MIC ratio), and the time above MIC, are good indicators of the drug dose-organism interaction. Time above the MIC is the important determinant of the activity of beta-lactams, macrolides, clindamycin, and linezolid. Free drug serum levels of these drugs should be above the MIC for at least 40%-50% of the dosing interval to produce adequate clinical and microbiological efficacy. Peak/MIC and 24-h AUC/MIC ratios are major determinants of the activity of aminoglycosides and fluoroquinolones. In general, peak/MIC ratios should exceed 8 and 24-h AUC/MIC values should be >100 to successfully treat gram-negative bacillary infections and to prevent the emergence of resistant organisms during therapy. The successful treatment of pneumococcal infections with fluoroquinolones and azithromycin appear to require 24-h AUC/MIC ratios of only 25-35. Mutation prevention concentrations are being reported for various fluoroquinolones with different pathogens, but their clinical significance has not yet been established. More information is needed on the role of PK/PD parameters and their magnitude for preventing mutations and the emergence of resistant organisms for most classes of antibiotics. (+info)
Self-protection against cell wall hydrolysis in Streptococcus milleri NMSCC 061 and analysis of the millericin B operon.
(27/7957)
Streptococcus milleri NMSCC 061 produces an endopeptidase, millericin B, which hydrolyzes the peptide moiety of susceptible cell wall peptidoglycan. The nucleotide sequence of a 4.9-kb chromosomal region showed three open reading frames (ORFs) and a putative tRNA(Leu) sequence. The three ORFs encode a millericin B preprotein (MilB), a putative immunity protein (MilF), and a putative transporter protein (MilT). The milB gene encodes a 277-amino-acid preprotein with an 18-amino-acid signal peptide with a consensus IIGG cleavage motif. The predicted protein encoded by milT is homologous to ABC (ATP-binding cassette) transporters of several bacteriocin systems and to proteins implicated in the signal-sequence-independent export of Escherichia coli hemolysin A. These similarities strongly suggest that the milT gene product is involved in the translocation of millericin B. The gene milF encodes a protein of 302 amino acids that shows similarities to the FemA and FemB proteins of Staphylococcus aureus, which are involved in the addition of glycine to a pentapeptide peptidoglycan precursor. Comparisons of the cell wall mucopeptide of S. milleri NMSCC 061(resistant to lysis by millericin B) and S. milleri NMSCC 051(sensitive) showed a single amino acid difference. Serial growth of S. milleri NMSCC 051 in a cell wall minimal medium containing an increased concentration of leucine resulted in the in vivo substitution of leucine for threonine in the mucopeptide of the cell wall. A cell wall variant of S. milleri NMSCC 051 (sensitive) that contained an amino acid substitution (leucine for threonine) within its peptidoglycan cross bridge showed partial susceptibility to millericin B. The putative tRNA(Leu) sequence located upstream of milB may be a cell wall-specific tRNA and could together with the milF protein, play a potential role in the addition of leucine to the pentapeptide peptidoglycan precursor and thereby, contributing to self-protection to millericin B in the producer strain. (+info)
Antimicrobial properties of pyridine-2,6-dithiocarboxylic acid, a metal chelator produced by Pseudomonas spp.
(28/7957)
Pyridine-2,6-dithiocarboxylic acid (pdtc) is a metal chelator produced by Pseudomonas spp. It has been shown to be involved in the biodegradation of carbon tetrachloride; however, little is known about its biological function. In this study, we examined the antimicrobial properties of pdtc and the mechanism of its antibiotic activity. The growth of Pseudomonas stutzeri strain KC, a pdtc-producing strain, was significantly enhanced by 32 microM pdtc. All nonpseudomonads and two strains of P. stutzeri were sensitive to 16 to 32 microM pdtc. In general, fluorescent pseudomonads were resistant to all concentrations tested. In competition experiments, strain KC demonstrated antagonism toward Escherichia coli. This effect was partially alleviated by 100 microM FeCl3. Less antagonism was observed in mutant derivatives of strain KC (CTN1 and KC657) which lack the ability to produce pdtc. A competitive advantage was restored to strain CTN1 by cosmid pT31, which restores pdtc production. pT31 also enhanced the pdtc resistance of all pdtc-sensitive strains, indicating that this plasmid contains elements responsible for resistance to pdtc. The antimicrobial effect of pdtc was reduced by the addition of Fe(III), Co(III), and Cu(II) and enhanced by Zn(II). Analyses by mass spectrometry determined that Cu(I):pdtc and Co(III):pdtc2 form immediately under our experimental conditions. Our results suggest that pdtc is an antagonist and that metal sequestration is the primary mechanism of its antimicrobial activity. It is also possible that Zn(II), if present, may play a role in pdtc toxicity. (+info)
Incidence of virulence factors and antibiotic resistance among Enterococci isolated from food.
(29/7957)
The incidence of virulence factors among 48 Enterococcus faecium and 47 Enterococcus faecalis strains from foods and their antibiotic susceptibility were investigated. No strain was resistant to all antibiotics, and for some strains, multiple resistances were observed. Of E. faecium strains, 10.4% were positive for one or more virulence determinants, compared to 78.7% of E. faecalis strains. Strains exhibiting virulence traits were not necessarily positive for all traits; thus, the incidence of virulence factors may be considered to be strain specific. (+info)
Differentiation of metronidazole-sensitive and -resistant clinical isolates of Helicobacter pylori by immunoblotting with antisera to the RdxA protein.
(30/7957)
Antimicrobial resistance in Helicobacter pylori is a serious and increasing problem, and the development of rapid, reliable methods for detecting resistance would greatly improve the selection of antibiotics used to treat gastric infection with this organism. We assessed whether detection of the RdxA protein could provide the basis for determining the susceptibility of H. pylori to metronidazole. In order to raise polyclonal antisera to RdxA, we cloned the rdxA gene from H. pylori strain 26695 into the commercial expression vector pMAL-c2, purified the resultant fusion protein by affinity chromatography, and used this recombinant RdxA preparation to immunize rabbits. We then used this specific anti-RdxA antibody to perform immunoblotting on whole bacterial cell lysates of 17 metronidazole-sensitive and 27 metronidazole-resistant clinical isolates of H. pylori. While a 24-kDa immunoreactive band corresponding to the RdxA protein was observed in all metronidazole-sensitive strains, this band was absent in 25 of 27 resistant isolates. Our results indicate that testing for the absence of the RdxA protein would identify the majority of clinical isolates that will respond poorly to metronidazole-containing eradication regimens and have implications for the development of assays capable of detecting metronidazole resistance in H. pylori. (+info)
Identification of aminoglycoside-modifying enzymes by susceptibility testing: epidemiology of methicillin-resistant Staphylococcus aureus in Japan.
(31/7957)
A multiple-primer PCR was used to identify genes encoding aminoglycoside-modifying enzymes in 381 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA). The technique used three sets of primers delineating specific DNA fragments of the aph(3')-III, ant(4')-I, and aac(6')-aph(2") genes, which influence the MICs of gentamicin, tobramycin, and lividomycin. Isolates with none of the three genes detected were susceptible to all three agents. Isolates with the aph(3')-III gene showed resistance to lividomycin (MIC > 1,024 microg/ml), and those with the ant(4')-I gene were resistant to tobramycin (MIC > or = 8 microg/ml). Isolates with only the aac(6')-aph(2") gene were resistant to gentamicin (MIC > or = 8 microg/ml) and tobramycin in decreasing order; those with both the ant(4')-I and aac(6')-aph(2") genes also were resistant to gentamicin and tobramycin, but in increasing order. Susceptibility testing, then, could detect specific genes. In 381 Japanese MRSA isolates, the ant(4')-I, aac(6')-aph(2"), and aph(3')-III genes were prevalent in 84.5, 61.7, and 8.9%, respectively. Isolates with only the ant(4')-I gene had coagulase type II or III, but isolates with both the ant(4')-I and aac(6')-aph(2") genes included all coagulase types. Most isolates with coagulase type IV or VII carried the aac(6')-aph(2") gene. Of the MRSA isolates with ant(4')-I and/or aac(6')-aph(2") genes, 97% were resistant to aminoglycosides in clinical use, but a new aminoglycoside, arbekacin, had excellent activity against these isolates. (+info)
Outbreak of infection with extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in a Mexican hospital.
(32/7957)
Thirty-one strains of Klebsiella pneumoniae (including 10 duplicates) from 21 septicemic pediatric patients (age, <2 months) were studied during a 4-month period (June to October 1996) in which the fatality rate was 62% (13 of 21). These isolates identified by the API 20E system yielded the same biotype. Pulsed-field gel electrophoresis experiments revealed the same clone in 31 strains. The isolates were multidrug-resistant but were still susceptible to ciprofloxacin, imipenem, and cefoxitin. A 135-kb plasmid was harbored in all of the isolates. No transconjugants were obtained that were resistant to ampicillin, cefotaxime, tetracycline, or gentamicin. Isoelectric focusing for beta-lactamases was performed on all strains, and three bands with pIs of 5.4, 7.6, and 8.2 were obtained. Of these, the pI 8.2 beta-lactamase had an extended-spectrum beta-lactamase phenotype. PCR amplification of both TEM- and SHV-type genes was obtained. The sequence analysis of the SHV PCR product indicated a mutation corresponding to the SHV-5 beta-lactamase. (+info)