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Journal ArticleDOI

Methicillin-resistant Staphylococcus aureus clinical strain with reduced vancomycin susceptibility.

01 Jul 1997-Journal of Antimicrobial Chemotherapy (Oxford University Press)-Vol. 40, Iss: 1, pp 135-136
TL;DR: Therapy was resumed with the com -bination of arbekacin and ampicillin/sulbactam which has been shown to have synergic activity against MRSA.
Abstract: (MRSA) with reduced suscept-ibility to vancomycin (MIC 8 mg/L). The strain was isolated from a surgical wound infection which was refrac -tory to vancomycin therapy.In May 1996, a 4 month-old male infant underwent heartsurgery for pulmonary atresia. Two weeks followingsurgery, the infant became febrile and developed a purulent discharge from the sternal surgical incision site;culture of the purulent material yielded MRSA. The patientwas treated with vancomycin (45 mg/kg daily) for 29 days,but fever and discharge of pus continued, and the C-reactive protein (CRP) remained elevated (40 mg/L). Thetreatment was changed to a combination of vancomycin andarbekacin (an aminoglycoside approved for MRSA infec-tion in Japan). After 12 days of this regimen, the purulentdischarge subsided, the wound began to heal, and the CRPdeclined from 40 to 9 mg/L. The antimicrobial therapy wasdiscontinued. However, 12 days later the surgical siteappeared inflamed with the development of a subcutaneousabscess accompanied by a sudden onset of fever and a raised CRP level of 35 mg/L. Therapy was resumed with the com -bination of arbekacin and ampicillin/sulbactam which hasbeen shown to have synergic activity against MRSA.
Citations
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Journal ArticleDOI
TL;DR: In an elegant series of clinical observations and laboratory studies published in 1880 and 1882, Ogston described staphylococcal disease and its role in sepsis and abscess formation.
Abstract: Micrococcus, which, when limited in its extent and activity, causes acute suppurative inflammation (phlegmon), produces, when more extensive and intense in its action on the human system, the most virulent forms of septicaemia and pyaemia.1 In an elegant series of clinical observations and laboratory studies published in 1880 and 1882, Ogston described staphylococcal disease and its role in sepsis and abscess formation.1,2 More than 100 years later, Staphylococcus aureus remains a versatile and dangerous pathogen in humans. The frequencies of both community-acquired and hospital-acquired staphylococcal infections have increased steadily, with little change in overall mortality. Treatment of these infections . . .

5,550 citations

Journal ArticleDOI
TL;DR: A multilocus sequence typing (MLST) scheme has been developed for Staphylococcus aureus and provides an unambiguous method for assigning MRSA and MSSA isolates to known clones or assigning them as novel clones via the Internet.
Abstract: A multilocus sequence typing (MLST) scheme has been developed for Staphylococcus aureus. The sequences of internal fragments of seven housekeeping genes were obtained for 155 S. aureus isolates from patients with community-acquired and hospital-acquired invasive disease in the Oxford, United Kingdom, area. Fifty-three different allelic profiles were identified, and 17 of these were represented by at least two isolates. The MLST scheme was highly discriminatory and was validated by showing that pairs of isolates with the same allelic profile produced very similar SmaI restriction fragment patterns by pulsed-field gel electrophoresis. All 22 isolates with the most prevalent allelic profile were methicillin-resistant S. aureus (MRSA) isolates and had allelic profiles identical to that of a reference strain of the epidemic MRSA clone 16 (EMRSA-16). Four MRSA isolates that were identical in allelic profile to the other major epidemic MRSA clone prevalent in British hospitals (clone EMRSA-15) were also identified. The majority of isolates (81%) were methicillin-susceptible S. aureus (MSSA) isolates, and seven MSSA clones included five or more isolates. Three of the MSSA clones included at least five isolates from patients with community-acquired invasive disease and may represent virulent clones with an increased ability to cause disease in otherwise healthy individuals. The most prevalent MSSA clone (17 isolates) was very closely related to EMRSA-16, and the success of the latter clone at causing disease in hospitals may be due to its emergence from a virulent MSSA clone that was already a major cause of invasive disease in both the community and hospital settings. MLST provides an unambiguous method for assigning MRSA and MSSA isolates to known clones or assigning them as novel clones via the Internet.

2,809 citations

Book
01 Jan 2006
TL;DR: This document describes standard broth dilution and microdilution and agar dilution techniques and it includes a series of procedures to standardize the way the tests are performed, and the performance, applications, and limitations of the current CLSI-recommended methods are described.
Abstract: Susceptibility testing is indicated for any organism that contributes to an infectious process warranting antimicrobial chemotherapy, if its susceptibility cannot be reliably predicted from knowledge of the organism’s identity. Susceptibility tests are most often indicated when the causative organism is thought to belong to a species capable of exhibiting resistance to commonly used antimicrobial agents. A variety of laboratory methods can be used to measure the in vitro susceptibility of bacteria to antimicrobial agents. This document describes standard broth dilution (macrodilution and microdilution [the microdilution method described in M07 is the same methodology outlined in ISO 20776-1]) and agar dilution techniques, and it includes a series of procedures to standardize the way the tests are performed. The performance, applications, and limitations of the current CLSI-recommended methods are also described. The supplemental information (M100 tables) presented with this standard represents the most current information for drug selection, interpretation, and quality control using the procedures standardized in M07. These tables, as in previous years, have been updated and should replace tables published in earlier years. Changes in the tables since the previous edition (M100-S18) appear in boldface type and are also summarized in the front of the document. Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard—Eighth Edition. CLSI document M07-A8 (ISBN 1-56238-689-1). Clinical and Laboratory Standards Institute, 940 West Valley Road, Suite 1400, Wayne, Pennsylvania 19087-1898 USA, 2009. The Clinical and Laboratory Standards Institute consensus process, which is the mechanism for moving a document through two or more levels of review by the health care community, is an ongoing process. Users should expect revised editions of any given document. Because rapid changes in technology may affect the procedures, methods, and protocols in a standard or guideline, users should replace outdated editions with the current editions of CLSI/NCCLS documents. Current editions are listed in the CLSI catalog and posted on our website at www.clsi.org. If your organization is not a member and would like to become one, and to request a copy of the catalog, contact us at: Telephone: 610.688.0100; Fax: 610.688.0700; E-Mail: customerservice@clsi.org; Website: www.clsi.org Product Name: Infobase 2010 Release Date: February 2010 This document is protected by international copyright laws.

2,314 citations

Journal ArticleDOI
TL;DR: 3 case histories-one involving Escherichia coli resistance to third-generation cephalosporins, another focusing on the emergence of vancomycin-resistant Staphylococcus aureus, and a third detailing multidrug resistance in Pseudomonas aeruginosa--are reviewed to illustrate the varied ways in which resistant bacteria develop.

1,697 citations

Journal ArticleDOI
TL;DR: This work analyzes an international collection of 912 MRSA and methicillin-susceptible S. aureus isolates to establish the likely evolutionary origins of each major MRSA clone, the genotype of the original MRSAclone and its MSSA progenitor, and the extent of acquisition and horizontal movement of the methiillin resistance genes.
Abstract: Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital-acquired infections that are becoming increasingly difficult to combat because of emerging resistance to all current antibiotic classes. The evolutionary origins of MRSA are poorly understood, no rational nomenclature exists, and there is no consensus on the number of major MRSA clones or the relatedness of clones described from different countries. We resolve all of these issues and provide a more thorough and precise analysis of the evolution of MRSA clones than has previously been possible. Using multilocus sequence typing and an algorithm, burst, we analyzed an international collection of 912 MRSA and methicillin-susceptible S. aureus (MSSA) isolates. We identified 11 major MRSA clones within five groups of related genotypes. The putative ancestral genotype of each group and the most parsimonious patterns of descent of isolates from each ancestor were inferred by using burst, which, together with analysis of the methicillin resistance genes, established the likely evolutionary origins of each major MRSA clone, the genotype of the original MRSA clone and its MSSA progenitor, and the extent of acquisition and horizontal movement of the methicillin resistance genes. Major MRSA clones have arisen repeatedly from successful epidemic MSSA strains, and isolates with decreased susceptibility to vancomycin, the antibiotic of last resort, are arising from some of these major MRSA clones, highlighting a depressing progression of increasing drug resistance within a small number of ecologically successful S. aureus genotypes.

1,653 citations

References
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Journal ArticleDOI
TL;DR: Substitution of a limited number of highly conserved aminoacids encoded by the rpoB gene appears to be the molecular mechanism responsible for "single step" high-level resistance to rifampicin in M tuberculosis, a marker of multidrug-resistant tuberculosis.

1,284 citations

Journal ArticleDOI
TL;DR: Rifabutin, given prophylactically, reduces the frequency of disseminated M. avium complex infection in patients with AIDS and CD4 counts < or = 200 per cubic millimeter.
Abstract: Background Disseminated Mycobacterium avium complex infection eventually develops in most patients with the acquired immunodeficiency syndrome (AIDS). This infection results in substantial morbidity and reduces survival by about six months. Methods We conducted two randomized, double-blind, multicenter trials of daily prophylactic treatment with either rifabutin (300 mg) or placebo. All the patients had AIDS and CD4 cell counts ≤ 200 per cubic millimeter. The primary end point was M. avium complex bacteremia as assessed monthly by blood culture. The secondary end points were signs and symptoms associated with disseminated M. avium complex infection, adverse events, hospitalization, and survival. Results In the first trial, M. avium complex bacteremia developed in 51 of 298 patients (17 percent) assigned to placebo and 24 of 292 patients (8 percent) assigned to rifabutin (P<0.001). In the second trial, bacteremia developed in 51 of 282 patients in the placebo group (18 percent) and 24 of 274 patients in th...

373 citations

Journal ArticleDOI
TL;DR: Azithromycin is active in treating Mycobacterium avium complex disease, but it has not been evaluated as primary prophylaxis in patients with human immunodeficiency virus (HIV) infection as discussed by the authors.
Abstract: Background Azithromycin is active in treating Mycobacterium avium complex disease, but it has not been evaluated as primary prophylaxis in patients with human immunodeficiency virus (HIV) infection. Because the drug is concentrated in macrophages and has a long half-life in tissue, there is a rationale for once-weekly dosing. Methods We compared three prophylactic regimens in a multicenter, double-blind, randomized trial involving 693 HIV-infected patients with fewer than 100 CD4 cells per cubic millimeter. The patients were assigned to receive rifabutin (300 mg daily), azithromycin (1200 mg weekly), or both drugs. They were monitored monthly with blood cultures for M. avium complex. Results In an intention-to-treat analysis, the incidence of disseminated M. avium complex infection at one year was 15.3 percent with rifabutin, 7.6 percent with azithromycin, and 2.8 percent with both drugs. The risk of the infection in the azithromycin group was half that in the rifabutin group (hazard ratio, 0.53; P = 0.00...

298 citations

Journal ArticleDOI
TL;DR: In patients with advanced AIDS, the prophylactic administration of clarithromycin is well tolerated, prevents M. avium complex infection, and reduces mortality.
Abstract: Background Disseminated infection with Mycobacterium avium complex is the most common opportunistic infection in patients with advanced stages of the acquired immunodeficiency syndrome (AIDS). We studied the efficacy and safety of prophylactic treatment with clarithromycin, a macrolide antibiotic. Methods We conducted a randomized, placebo-controlled, double-blind study of clarithromycin in patients with AIDS in the United States and Europe. Entry criteria included blood cultures that were negative for M. avium complex, a Karnofsky performance score of 50 or higher, a CD4 cell count of 100 or less per cubic millimeter, and a life expectancy of at least six months. Results After the first interim analysis, the study was stopped. M. avium complex infection developed in 19 of the 333 patients (6 percent) assigned to clarithromycin and in 53 of the 334 (16 percent) assigned to placebo (adjusted hazard ratio, 0.31; 95 percent confidence interval, 0.18 to 0.53; P<0.001). During the follow-up period of about 10 ...

271 citations

Journal ArticleDOI
TL;DR: The probable mechanism of clarithromycin resistance in M. avium is defined and in vivo evidence that mutational resistance is random and selection-directed is provided, and the same point mutations observed in vivo are revealed.
Abstract: The peptidyltransferase region of the 23S rRNA gene (the probable target site for the macrolides) was investigated in blood isolates of Mycobacterium avium recovered from 38 patients before and after the development of clarithromycin resistance. Point mutations were identified in 100% of the 74 resistant relapse blood isolates but in none of 69 susceptible pretreatment isolates. Multiple mutations were identified in isolates from 23 (61%) of 38 patients. Of the 63 identified mutations, 95% involved adenine at bp 2058. Single-colony clones from cultures that were mixtures of more than one mutation revealed a single mutation within each clone. Pulsed field gel electrophoresis of genomic DNA restriction fragments revealed that 13 (81%) of 16 multiple mutations identified in the same patient were derived from a single infecting strain. In vitro investigation revealed the same point mutations observed in vivo. This study defines the probable mechanism of clarithromycin resistance in M. avium and provides in vivo evidence that mutational resistance is random and selection-directed.

107 citations