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Fred C Tenover

Publications and source records attributed to Fred C Tenover.

At least 19 recordsLinked to original sources
PubMed2006

Rapid multiplex PCR assay for identification of USA300 community-associated methicillin-resistant Staphylococcus aureus isolates.

Recent reports have noted a discernible increase in the number of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections in patients without traditional risk factors. In the United States, the most prominent CA-MRSA strain encodes Panton-Valentine leukocidin (PVL) cytotoxin genes, belongs to pulsed field gel electrophoresis type USA300 and multilocus sequence type 8, and carries staphylococcal cassette chromosome mec (SCCmec) type IV. At present, molecular characterization of MRSA strains, such as USA300, can be time-consuming and is often beyond the technical capability of many clinical laboratories, making routine identification difficult. We analyzed the chromosomal regions flanking the SCCmec element in 44 USA300 MRSA isolates and identified a signature "AT repeat" sequence within the conserved hypothetical gene SACOL0058 located 1.4 kb downstream of the 3' end of the J1-SCCmec chromosomal junction. Only USA300 isolates tested contained a sequence of > or =6 AT repeats in combination with PVL (e.g., related USA500 or Iberian strains had > or =6 AT repeats but were PVL negative). Using a locked nucleic acid primer specific for > or =6 AT repeats in combination with primers to detect PVL, we developed a multiplex PCR assay specific for the identification of USA300 strains. Multiplex results were 100% concordant with DNA sequencing, suggesting that the method has promise as a means of rapidly identifying USA300 isolates.

Bacterial Proteins↗
PubMed2006

Management of persistent bacteremia caused by methicillin-resistant Staphylococcus aureus: a survey of infectious diseases consultants.

We conducted a survey in 2005 of infectious diseases consultants and asked about persistent bacteremia due to methicillin-resistant Staphylococcus aureus. Many consultants perceived an increase in the frequency of illness, and, when presented with vancomycin minimum inhibitory concentrations approaching the limit of the susceptible range, most consultants indicated that they would switch to newer antimicrobial agents for treatment.

Anti-Bacterial Agents↗
PubMed2006

Investigation of inducible clindamycin and telithromycin resistance in isolates of beta-hemolytic streptococci.

We evaluated the accuracy of an erythromycin-clindamycin double-disk test (D-zone test) and an erythromycin-telithromycin D-zone test for detection of inducible resistance in isolates of beta-hemolytic streptococci with erythromycin resistance. The results of these tests were compared to results of a broth microdilution (BMD) induction test using combinations of erythromycin and either clindamycin or telithromycin. Of 29 erythromycin-resistant, clindamycin-susceptible isolates, 16 were positive by the erythromycin-clindamycin D-zone test; all of these demonstrated inducible clindamycin resistance by BMD. Twelve isolates were D-zone test-negative, did not demonstrate inducible resistance by BMD, and were positive for a mef determinant. Of 39 erythromycin-resistant, telithromycin-susceptible isolates, 13 were erythromycin-telithromycin D-zone test-positive, 19 questionably positive (unclear blunting of the zone), and 7 were D-zone test-negative. The erythromycin-telithromycin D-zone test result did not correlate with inducible resistance by BMD or the presence of an erm or mef gene. These results demonstrate that the erythromycin-clindamycin D-zone and BMD induction tests accurately detect inducible clindamycin resistance, but the erythromycin-telithromycin D-zone test is not reliable for detecting inducible telithromycin resistance.

Anti-Bacterial Agents↗
PubMed2006

Mechanisms of antimicrobial resistance in bacteria.

The treatment of bacterial infections is increasingly complicated by the ability of bacteria to develop resistance to antimicrobial agents. Antimicrobial agents are often categorized according to their principal mechanism of action. Mechanisms include interference with cell wall synthesis (eg, beta-lactams and glycopeptide agents), inhibition of protein synthesis (macrolides and tetracyclines), interference with nucleic acid synthesis (fluoroquinolones and rifampin), inhibition of a metabolic pathway (trimethoprim-sulfamethoxazole), and disruption of bacterial membrane structure (polymyxins and daptomycin). Bacteria may be intrinsically resistant to > or =1 class of antimicrobial agents, or may acquire resistance by de novo mutation or via the acquisition of resistance genes from other organisms. Acquired resistance genes may enable a bacterium to produce enzymes that destroy the antibacterial drug, to express efflux systems that prevent the drug from reaching its intracellular target, to modify the drug's target site, or to produce an alternative metabolic pathway that bypasses the action of the drug. Acquisition of new genetic material by antimicrobial-susceptible bacteria from resistant strains of bacteria may occur through conjugation, transformation, or transduction, with transposons often facilitating the incorporation of the multiple resistance genes into the host's genome or plasmids. Use of antibacterial agents creates selective pressure for the emergence of resistant strains. Herein 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.

Cephalosporin Resistance↗
PubMed2006

Mechanisms of antimicrobial resistance in bacteria.

The treatment of bacterial infections is increasingly complicated by the ability of bacteria to develop resistance to antimicrobial agents. Antimicrobial agents are often categorized according to their principal mechanism of action. Mechanisms include interference with cell wall synthesis (e.g., beta-lactams and glycopeptide agents), inhibition of protein synthesis (macrolides and tetracyclines), interference with nucleic acid synthesis (fluoroquinolones and rifampin), inhibition of a metabolic pathway (trimethoprim-sulfamethoxazole), and disruption of bacterial membrane structure (polymyxins and daptomycin). Bacteria may be intrinsically resistant to > or =1 class of antimicrobial agents, or may acquire resistance by de novo mutation or via the acquisition of resistance genes from other organisms. Acquired resistance genes may enable a bacterium to produce enzymes that destroy the antibacterial drug, to express efflux systems that prevent the drug from reaching its intracellular target, to modify the drug's target site, or to produce an alternative metabolic pathway that bypasses the action of the drug. Acquisition of new genetic material by antimicrobial-susceptible bacteria from resistant strains of bacteria may occur through conjugation, transformation, or transduction, with transposons often facilitating the incorporation of the multiple resistance genes into the host's genome or plasmids. Use of antibacterial agents creates selective pressure for the emergence of resistant strains. Herein 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.

Adult↗
PubMed2006

Multicenter evaluation of the Etest and disk diffusion methods for differentiating daptomycin-susceptible from non-daptomycin-susceptible Staphylococcus aureus isolates.

Daptomycin is a novel cyclic lipopeptide that is approved by the U.S. Food and Drug Administration for the treatment of complicated skin and skin structure infections associated with Staphylococcus aureus and other gram-positive pathogens and also staphylococcal bacteremia, including right-sided endocarditis. The Clinical and Laboratory Standards Institute (CLSI) established "susceptible-only" interpretive criteria for broth microdilution (BMD) and disk diffusion (DD) testing of daptomycin in 2005. However, a series of S. aureus isolates have been recovered with daptomycin MICs in the nonsusceptible range (i.e., MICs of >1 microg/ml). The objective of this study was to determine the ability of the Etest and DD methods to differentiate daptomycin-susceptible from nonsusceptible isolates of S. aureus compared to the results of the CLSI BMD reference method. There was a good correlation between Etest MIC results and the results of BMD among laboratories (r = 0.86 to 0.88), with 95.3% of the Etest MICs within a +/-1 log(2) dilution of the BMD MIC result. A total of 92 of 102 (90.2%) non-daptomycin-susceptible isolates of S. aureus identified by BMD in two participating laboratories were also classified as nonsusceptible by Etest. However, the very major and major error rates reported by one of the participating laboratories were 13.5 and 4.0%, respectively, primarily due to the absence of an intermediate category. The DD method, however, did not reliably differentiate daptomycin-susceptible from non-daptomycin-susceptible isolates. In 2005, daptomycin disks were voluntarily removed from the market by Cubist Pharmaceuticals. The disk diffusion breakpoints were subsequently removed from the CLSI M100 standard in 2006.

Anti-Bacterial Agents↗
PubMed2006

Characterization of a strain of community-associated methicillin-resistant Staphylococcus aureus widely disseminated in the United States.

A highly stable strain of Staphylococcus aureus with a pulsed-field gel electrophoresis type of USA300 and multilocus sequence type 8 has been isolated from patients residing in diverse geographic regions of the United States. This strain, designated USA300-0114, is a major cause of skin and soft tissue infections among persons in community settings, including day care centers and correctional facilities, and among sports teams, Native Americans, men who have sex with men, and military recruits. The organism is typically resistant to penicillin, oxacillin, and erythromycin (the latter mediated by msrA) and carries SCCmec type IVa. This strain is variably resistant to tetracycline [mediated by tet(K)]; several recent isolates have decreased susceptibility to fluoroquinolones. S. aureus USA300-0114 harbors the genes encoding the Panton-Valentine leucocidin toxin. DNA sequence analysis of the direct repeat units within the mec determinant of 30 USA300-0114 isolates revealed differences in only a single isolate. Plasmid analysis identified a common 30-kb plasmid that hybridized with blaZ and msrA probes and a 3.1-kb cryptic plasmid. A 4.3-kb plasmid encoding tet(K) and a 2.6-kb plasmid encoding ermC were observed in a few isolates. DNA microarray analysis was used to determine the genetic loci for a series of virulence factors and genes associated with antimicrobial resistance. Comparative genomics between USA300-0114 and three other S. aureus lineages (USA100, USA400, and USA500) defined a set of USA300-0114-specific genes, which may facilitate the strain's pathogenesis within diverse environments.

Community-Acquired Infections↗
PubMed2006

Multilaboratory evaluation of disk diffusion antimicrobial susceptibility testing of Neisseria meningitidis isolates.

In 2005, the Clinical and Laboratory Standards Institute published MIC interpretive criteria for 13 antimicrobial agents used for either therapy or prophylaxis of Neisseria meningitidis infections. The MIC method includes the use of lysed horse blood-supplemented Mueller-Hinton broth with incubation in 5% CO2 for 20 to 24 h. Since some clinical laboratories might prefer the option of disk diffusion testing for infrequently encountered isolates a multicenter collaborative study was conducted to evaluate the reproducibility of a disk diffusion method for testing isolates of N. meningitidis. Interpretive criteria were developed for 12 antimicrobial agents. Four laboratories tested a common collection of 50 meningococcal strains and then tested 25 unique isolates per laboratory. Isolates were tested using Mueller-Hinton sheep blood agar plates incubated for 20 to 24 h in 5% CO2; they were also tested by the reference broth microdilution method in parallel. Pooling of the MIC and disk diffusion data from the common and unique isolates provided a sufficient sample size to develop susceptible, intermediate, and resistant zone diameter interpretive criteria using the error rate-bounded method for the following agents: chloramphenicol, trimethoprim-sulfamethoxazole, ciprofloxacin, and rifampin. Due to the lack of resistant strains at the present time, "susceptible only" interpretive criteria were proposed for cefotaxime, ceftriaxone, meropenem, azithromycin, and minocycline. The numbers of minor interpretive errors with penicillin and ampicillin disk tests were unacceptably high and precluded recommended testing of those agents by the disk method. However, amdinocillin, an agent that preferentially binds to the altered penicillin binding protein responsible for diminished penicillin susceptibility, has potential utility as a surrogate screening reagent for ampicillin resistance. A disk diffusion breakpoint was derived for nalidixic acid to serve as a surrogate marker for gyrase A mutations associated with diminished fluoroquinolone susceptibility. Disk diffusion testing with meningococci can be performed in a reproducible manner with several antimicrobial agents and represents a practical and cost-effective option for testing sporadic clinical isolates or for surveillance purposes by resource-limited laboratories.

Anti-Bacterial Agents↗
PubMed2006

Class 1 integrons in resistant Escherichia coli and Klebsiella spp., US hospitals.

We examined Escherichia coli and Klebsiella spp. from US hospitals for class 1 integrons. Of 320 isolates, 181 (57%) were positive; association of integrons with resistance varied by drug and organism. Thus, determining integron epidemiology will improve understanding of how antibacterial resistance determinants spread in the United States.

DNA, Bacterial↗
PubMed2006

Carbapenem resistance in Klebsiella pneumoniae not detected by automated susceptibility testing.

Detecting beta-lactamase-mediated carbapenem resistance among Klebsiella pneumoniae isolates and other Enterobacteriaceae is an emerging problem. In this study, 15 blaKPC-positive Klebsiella pneumoniae that showed discrepant results for imipenem and meropenem from 4 New York City hospitals were characterized by isoelectric focusing; broth microdilution (BMD); disk diffusion (DD); and MicroScan, Phoenix, Sensititre, VITEK, and VITEK 2 automated systems. All 15 isolates were either intermediate or resistant to imipenem and meropenem by BMD; 1 was susceptible to imipenem by DD. MicroScan and Phoenix reported 1 (6.7%) and 2 (13.3%) isolates, respectively, as imipenem susceptible. VITEK and VITEK 2 reported 10 (67%) and 5 (33%) isolates, respectively, as imipenem susceptible. By Sensititre, 13 (87%) isolates were susceptible to imipenem, and 12 (80%) were susceptible to meropenem. The VITEK 2 Advanced Expert System changed 2 imipenem MIC results from >16 ?g/mL to <2 ?g/mL but kept the interpretation as resistant. The recognition of carbapenem-resistant K. pneumoniae continues to challenge automated susceptibility systems.

Anti-Bacterial Agents↗
PubMed2005

Prevalence of Staphylococcus aureus nasal colonization in the United States, 2001-2002.

BACKGROUND: Staphylococcus aureus is a common cause of disease, particularly in colonized persons. Although methicillin-resistant S. aureus (MRSA) infection has become increasingly reported, population-based S. aureus and MRSA colonization estimates are lacking. METHODS: Nasal samples for S. aureus culture and sociodemographic data were obtained from 9622 persons > or = 1 year old as part of the National Health and Nutrition Examination Survey, 2001-2002. After screening for oxacillin susceptibility, MRSA and selected methicillin-susceptible S. aureus isolates were tested for antimicrobial susceptibility, pulsed-field gel electrophoresis clonal type, toxin genes (e.g., for Panton-Valentine leukocidin [PVL]), and staphylococcal cassette chromosome mec (SCCmec) type I-IV genes. RESULTS: For 2001-2002, national S. aureus and MRSA colonization prevalence estimates were 32.4% (95% confidence interval [CI], 30.7%-34.1%) and 0.8% (95% CI, 0.4%-1.4%), respectively, and population estimates were 89.4 million persons (95% CI, 84.8-94.1 million persons) and 2.3 million persons (95% CI, 1.2-3.8 million persons), respectively. S. aureus colonization prevalence was highest in participants 6-11 years old. MRSA colonization was associated with age > or = 60 years and being female but not with recent health-care exposure. In unweighted analyses, the SCCmec type IV gene was more frequent in isolates from participants of younger age and of non-Hispanic black race/ethnicity; the PVL gene was present in 9 (2.4%) of 372 of isolates tested. CONCLUSIONS: Many persons in the United States are colonized with S. aureus; prevalence rates differ demographically. MRSA colonization prevalence, although low nationally in 2001-2002, may vary with demographic and organism characteristics.

Adolescent↗
PubMed2005

Risk factors for colonization with methicillin-resistant Staphylococcus aureus (MRSA) in patients admitted to an urban hospital: emergence of community-associated MRSA nasal carriage.

BACKGROUND: Surveillance cultures performed at hospital admission have been recommended to identify patients colonized with methicillin-resistant Staphylococcus aureus (MRSA) but require substantial resources. We determined the prevalence of and risk factors for MRSA colonization at the time of hospital admission among patients cared for at a public urban hospital. METHODS: Anterior nares cultures were obtained within 48 h after admission during a 1-month period. A case-control study and molecular typing studies were performed. RESULTS: A total of 53 (7.3%) of 726 patients had a nares culture positive for MRSA, and 119 (16.4%) had a nares culture that was positive for methicillin-susceptible S. aureus. In multivariate analysis, risk factors for MRSA colonization included antibiotic use within 3 months before admission (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.2-5.0), hospitalization during the past 12 months (OR, 4.0; 95% CI, 2.0-8.2), diagnosis of skin or soft-tissue infection at admission (OR, 3.4; 95% CI, 1.5-7.9), and HIV infection. A total of 47 (89%) of 53 case patients colonized with MRSA had at least 1 of these independent risk factors, in contrast to 343 (51%) of 673 control patients (OR, 7.5; 95% CI, 3.2 -17.9). Molecular typing demonstrated that 16 (30%) of 53 MRSA nares isolates (2.2% of the 726 isolates) belonged to the USA300 community-associated MRSA (CA-MRSA) genotype. CONCLUSION: The prevalence of MRSA colonization at the time of patient admission was high (>7%). Limiting surveillance cultures to patients with >or=1 of the identified risk factors may allow for targeted screening. The emergence of CA-MRSA colonization represents a new, unrecognized reservoir of MRSA within hospitals, potentially increasing the risk for horizontal transmission.

Adolescent↗
PubMed2005

A clone of methicillin-resistant Staphylococcus aureus among professional football players.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) is an emerging cause of infections outside of health care settings. We investigated an outbreak of abscesses due to MRSA among members of a professional football team and examined the transmission and microbiologic characteristics of the outbreak strain. METHODS: We conducted a retrospective cohort study and nasal-swab survey of 84 St. Louis Rams football players and staff members. S. aureus recovered from wound, nasal, and environmental cultures was analyzed by means of pulsed-field gel electrophoresis (PFGE) and typing for resistance and toxin genes. MRSA from the team was compared with other community isolates and hospital isolates. RESULTS: During the 2003 football season, eight MRSA infections occurred among 5 of the 58 Rams players (9 percent); all of the infections developed at turf-abrasion sites. MRSA infection was significantly associated with the lineman or linebacker position and a higher body-mass index. No MRSA was found in nasal or environmental samples; however, methicillin-susceptible S. aureus was recovered from whirlpools and taping gel and from 35 of the 84 nasal swabs from players and staff members (42 percent). MRSA from a competing football team and from other community clusters and sporadic cases had PFGE patterns that were indistinguishable from those of the Rams' MRSA; all carried the gene for Panton-Valentine leukocidin and the gene complex for staphylococcal-cassette-chromosome mec type IVa resistance (clone USA300-0114). CONCLUSIONS: We describe a highly conserved, community-associated MRSA clone that caused abscesses among professional football players and that was indistinguishable from isolates from various other regions of the United States.

Abscess↗
PubMed2005

Management of anthrax meningitis.

Meningitis due to infection with Bacillus anthracis is considered an infrequent manifestation of the disease but one associated with high mortality. The bioterrorism event in the USA in the autumn of 2001 demonstrated our need for a better understanding of anthrax meningitis, as well as management and antimicrobial therapy. However, human clinical trials are not possible and animal experiments to guide such therapy are limited. An approach to the treatment of anthrax meningitis, based on the pathogenicity of B anthracis, the pharmacokinetics and pharmacodynamics of individual antimicrobial agents, studies of anthrax post-exposure prophylaxis in non-human primates, experience with antimicrobial susceptibility patterns of the 2001 outbreak strain, and the clinical experience with inhalational anthrax cases during the 2001 outbreak is presented. These outbreak data, the failure of previous single-drug regimens, the concerns of resistance, and the need for coverage for other causes of bacterial mengingitis suggest initial treatment of suspected anthrax meningitis should anchor on an intravenous fluoroquinolone and should include one or two other agents with activity against B anthracis and good penetration into the central nervous system. Such other agents include penicillin, ampicillin, meropenem, vancomycin, and rifampicin.

Animals↗
PubMed2005

Vancomycin-resistant staphylococci and enterococci: epidemiology and control.

PURPOSE OF REVIEW: This review updates information on the development and spread of vancomycin resistance in staphylococci and enterococci. RECENT FINDINGS: New information on the genetic characterization of vancomycin-resistant Staphylococcus aureus isolates from the US indicates that each of the four was the result of an independent genetic event. New data suggest that vancomycin-intermediate S. aureus isolates, particularly those showing heteroresistance, are clinically significant. Finally, vancomycin-resistant enterococci continue to be reported from around the world. Novel infection control measures, however, may aid in reducing the spread of these organisms in healthcare settings. SUMMARY: The exchange of genetic information, particularly the vanA gene, between and among staphylococci and enterococci will continue to challenge physicians, microbiologists, and infection control practitioners in efforts to identify, treat, and prevent infections with these pathogens.

Enterococcus↗
PubMed2005

Comparison of Tn1546-like elements in vancomycin-resistant Staphylococcus aureus isolates from Michigan and Pennsylvania.

In 2002, the first two clinical isolates of vancomycin-resistant Staphylococcus aureus (VRSA) containing vanA were recovered in Michigan and Pennsylvania. Tn1546, a mobile genetic element that encodes high-level vancomycin resistance in enterococci, was present in both isolates. With PCR and DNA sequence analysis, we compared the Tn1546 elements from each isolate to the prototype Tn1546 element. The Michigan VRSA element was identical to the prototype Tn1546 element. The Pennsylvania VRSA element showed three distinct modifications: a deletion of nucleotides 1 to 3098 at the 5' end, which eliminated the orf1 region; an 809-bp IS1216V-like element inserted before nucleotide 3099 of Tn1546; and an inverted 1,499-bp IS1251-like element inserted into the vanSH intergenic region. These differences in the Tn1546-like elements indicate that the first two VRSA isolates were the result of independent genetic events.

DNA Transposable Elements↗