32 results on '"Rice LB"'
Search Results
2. State-of-the-Art Review: Persistent Enterococcal Bacteremia.
- Author
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Rogers R and Rice LB
- Subjects
- Humans, Anti-Bacterial Agents therapeutic use, Bacteremia diagnosis, Bacteremia drug therapy, Bacterial Infections drug therapy, Gram-Positive Bacterial Infections diagnosis, Gram-Positive Bacterial Infections drug therapy
- Abstract
Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. Both authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest.
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- 2024
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3. Houston, We Have a Problem: Reports of Clostridioides difficile Isolates With Reduced Vancomycin Susceptibility.
- Author
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Greentree DH, Rice LB, and Donskey CJ
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- Humans, Vancomycin pharmacology, Vancomycin therapeutic use, Clostridioides, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Clostridioides difficile, Clostridium Infections drug therapy, Clostridium Infections epidemiology
- Abstract
During the past 4 decades, oral vancomycin has been a mainstay of Clostridioides difficile infection (CDI) therapy with no reports of treatment failure due to emergence of vancomycin resistance. However, C. difficile isolates with high-level phenotypic resistance to vancomycin have recently been reported in 3 distinct geographic regions. There is an urgent need for surveillance to determine if strains with reduced vancomycin susceptibility are circulating in other areas. In a Cleveland-area hospital, screening of 176 CDI stool specimens yielded no C. difficile isolates with reduced vancomycin susceptibility and highlighted the potential for false-positive results due to contamination with vancomycin-resistant enterococci. Additional studies are needed to clarify whether reduced vancomycin susceptibility is an emerging problem that will alter clinical practice. Clinicians should alert their health department if they observe a substantial increase in the frequency of vancomycin treatment failure in patients diagnosed with CDI with no alternative explanation for diarrhea., Competing Interests: Potential conflicts of interest. C. J. D. has received research funding from Clorox, PDI, and Pfizer. All other authors report no potential conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2022.)
- Published
- 2022
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4. Fosfomycin for Injection (ZTI-01) Versus Piperacillin-tazobactam for the Treatment of Complicated Urinary Tract Infection Including Acute Pyelonephritis: ZEUS, A Phase 2/3 Randomized Trial.
- Author
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Kaye KS, Rice LB, Dane AL, Stus V, Sagan O, Fedosiuk E, Das AF, Skarinsky D, Eckburg PB, and Ellis-Grosse EJ
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- Adult, Aged, Aged, 80 and over, Bacterial Load, Drug Resistance, Bacterial, Female, Humans, Injections, Male, Microbial Sensitivity Tests, Middle Aged, Piperacillin, Tazobactam Drug Combination administration & dosage, Piperacillin, Tazobactam Drug Combination adverse effects, Pyelonephritis etiology, Treatment Outcome, Urinary Tract Infections etiology, Young Adult, Anti-Bacterial Agents administration & dosage, Fosfomycin administration & dosage, Piperacillin, Tazobactam Drug Combination therapeutic use, Pyelonephritis drug therapy, Urinary Tract Infections drug therapy
- Abstract
Background: ZTI-01 (fosfomycin for injection) is an epoxide antibiotic with a differentiated mechanism of action (MOA) inhibiting an early step in bacterial cell wall synthesis. ZTI-01 has broad in vitro spectrum of activity, including multidrug-resistant Gram-negative pathogens, and is being developed for treatment of complicated urinary tract infection (cUTI) and acute pyelonephritis (AP) in the United States., Methods: Hospitalized adults with suspected or microbiologically confirmed cUTI/AP were randomized 1:1 to 6 g ZTI-01 q8h or 4.5 g intravenous (IV) piperacillin-tazobactam (PIP-TAZ) q8h for a fixed 7-day course (no oral switch); patients with concomitant bacteremia could receive up to 14 days., Results: Of 465 randomized patients, 233 and 231 were treated with ZTI-01 and PIP-TAZ, respectively. In the microbiologic modified intent-to-treat (m-MITT) population, ZTI-01 met the primary objective of noninferiority compared with PIP-TAZ with overall success rates of 64.7% (119/184 patients) vs 54.5% (97/178 patients), respectively; treatment difference was 10.2% (95% confidence interval [CI]: -0.4, 20.8). Clinical cure rates at test of cure (TOC, day 19-21) were high and similar between treatments (90.8% [167/184] vs 91.6% [163/178], respectively). In post hoc analysis using unique pathogens typed by pulsed-field gel electrophoresis, overall success rates at TOC in m-MITT were 69.0% (127/184) for ZTI-01 versus 57.3% (102/178) for PIP-TAZ (difference 11.7% 95% CI: 1.3, 22.1). ZTI-01 was well tolerated. Most treatment-emergent adverse events, including hypokalemia and elevated serum aminotransferases, were mild and transient., Conclusions: ZTI-01 was effective for treatment of cUTI including AP and offers a new IV therapeutic option with a differentiated MOA for patients with serious Gram-negative infections., Clinical Trial Registration: NCT02753946., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.)
- Published
- 2019
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5. Reply to Koehler et al.
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Beganovic M, Luther MK, Rice LB, Arias CA, Rybak MJ, and LaPlante KL
- Subjects
- Anti-Bacterial Agents, Enterococcus faecalis, Humans, Anti-Infective Agents, Endocarditis, Endocarditis, Bacterial
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- 2019
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6. A Review of Combination Antimicrobial Therapy for Enterococcus faecalis Bloodstream Infections and Infective Endocarditis.
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Beganovic M, Luther MK, Rice LB, Arias CA, Rybak MJ, and LaPlante KL
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- Ampicillin therapeutic use, Ceftriaxone therapeutic use, Cephalosporins therapeutic use, Clinical Trials as Topic, Drug Synergism, Drug Therapy, Combination, Gram-Positive Bacterial Infections complications, Humans, Microbial Sensitivity Tests, Vancomycin-Resistant Enterococci drug effects, Anti-Bacterial Agents therapeutic use, Bacteremia drug therapy, Endocarditis, Bacterial drug therapy, Enterococcus faecalis drug effects, Gram-Positive Bacterial Infections drug therapy
- Abstract
Enterococci, one of the most common causes of hospital-associated infections, are responsible for substantial morbidity and mortality. Enterococcus faecalis, the more common and virulent species, causes serious high-inoculum infections, namely infective endocarditis, that are associated with cardiac surgery and mortality rates that remained unchanged for the last 30 years. The best cures for these infections are observed with combination antibiotic therapy; however, optimal treatment has not been fully elucidated. It is the purpose of this review to highlight treatment options and their limitations, and provide direction for future investigative efforts to aid in the treatment of these severe infections. While ampicillin plus ceftriaxone has emerged as a preferred treatment option, mortality rates continue to be high, and from a safety standpoint, ceftriaxone, unlike other cephalosporins, promotes colonization with vancomycin resistant-enterococci due to high biliary concentrations. More research is needed to improve patient outcomes from this high-mortality disease.
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- 2018
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7. In memoriam: John P. Quinn, MD.
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Perez F, Arias CA, Bush K, Drusano GL, Lolans K, Munoz-Price LS, Nicolau DP, Queenan AM, Rice LB, Segreti J, Shlaes DM, Weinstein RA, and Bonomo RA
- Subjects
- Anti-Bacterial Agents isolation & purification, Drug Discovery methods, Gram-Negative Bacterial Infections drug therapy, History, 20th Century, History, 21st Century, Humans, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Drug Resistance, Bacterial, Gram-Negative Bacteria drug effects, Gram-Negative Bacterial Infections microbiology
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- 2014
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8. Gastrointestinal bacteria will have its way.
- Author
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Rice LB
- Subjects
- Humans, Anti-Bacterial Agents administration & dosage, Ciprofloxacin administration & dosage, Drug Resistance, Bacterial, Escherichia coli drug effects, Feces microbiology
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- 2012
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9. Rapid diagnostics and appropriate antibiotic use.
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Rice LB
- Subjects
- Diagnosis, Differential, Humans, Time Factors, Anti-Bacterial Agents therapeutic use, Bacterial Infections diagnosis, Bacterial Infections drug therapy, Molecular Diagnostic Techniques methods, Virus Diseases diagnosis, Virus Diseases drug therapy
- Abstract
Most antibiotics are prescribed by physicians lacking postgraduate training in infectious diseases. As such, prescribing physicians have varying levels of interest and sophistication in thinking about how to use molecular and microbiological data to inform therapeutic choices. Strategies designed to modify physician antimicrobial-prescribing practices must therefore choose simplicity over complexity and must acknowledge our fundamental ignorance of many of the specifics of antibiotic-microorganism interactions. They must also acknowledge the critical nature of bacterial illnesses in hospitalized patients and the importance of delivering effective antimicrobial therapy early in the illness. "Back-end" strategies that evaluate therapy at defined intervals will be more readily accepted than strategies limiting physician choices early in the illness. It is therefore critical that we develop rapid and reliable microbiological assays, evidence-based recommendations on appropriate durations of therapy, and accurate surrogate markers of infection resolution.
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- 2011
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10. Characterization of blaKPC-containing Klebsiella pneumoniae isolates detected in different institutions in the Eastern USA.
- Author
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Endimiani A, Hujer AM, Perez F, Bethel CR, Hujer KM, Kroeger J, Oethinger M, Paterson DL, Adams MD, Jacobs MR, Diekema DJ, Hall GS, Jenkins SG, Rice LB, Tenover FC, and Bonomo RA
- Subjects
- Anti-Bacterial Agents pharmacology, Bacterial Typing Techniques, Cluster Analysis, DNA Fingerprinting, DNA, Bacterial genetics, Electrophoresis, Gel, Pulsed-Field, Genotype, Humans, Isoelectric Focusing, Isoelectric Point, Klebsiella pneumoniae drug effects, Microbial Sensitivity Tests, Molecular Epidemiology, Sequence Analysis, DNA, United States, beta-Lactamases chemistry, Klebsiella Infections microbiology, Klebsiella pneumoniae enzymology, Klebsiella pneumoniae isolation & purification, beta-Lactam Resistance, beta-Lactamases biosynthesis
- Abstract
Background: The emergence of bla(KPC)-containing Klebsiella pneumoniae (KPC-Kp) isolates is attracting significant attention. Outbreaks in the Eastern USA have created serious treatment and infection control problems. A comparative multi-institutional analysis of these strains has not yet been performed., Methods: We analysed 42 KPC-Kp recovered during 2006-07 from five institutions located in the Eastern USA. Antimicrobial susceptibility tests, analytical isoelectric focusing (aIEF), PCR and sequencing of bla genes, PFGE and rep-PCR were performed. Results By in vitro testing, KPC-Kp isolates were highly resistant to all non-carbapenem beta-lactams (MIC(90)s >or= 128 mg/L). Among carbapenems, MIC(50/90)s were 4/64 mg/L for imipenem and meropenem, 4/32 mg/L for doripenem and 8/128 for ertapenem. Combinations of clavulanate or tazobactam with a carbapenem or cefepime did not significantly lower the MIC values. Genetic analysis revealed that the isolates possessed the following bla genes: bla(KPC-2) (59.5%), bla(KPC-3) (40.5%), bla(TEM-1) (90.5%), bla(SHV-11) (95.2%) and bla(SHV-12) (50.0%). aIEF of crude beta-lactamase extracts from these strains supported our findings, showing beta-lactamases at pIs of 5.4, 7.6 and 8.2. The mean number of beta-lactamases was 3.5 (range 3-5). PFGE demonstrated that 32 (76.2%) isolates were clonally related (type A). Type A KPC-Kp isolates (20 bla(KPC-2) and 12 bla(KPC-3)) were detected in each of the five institutions. rep-PCR showed patterns consistent with PFGE., Conclusions: We demonstrated the complex beta-lactamase background of KPC-Kp isolates that are emerging in multiple centres in the Eastern USA. The prevalence of a single dominant clone suggests that interstate transmission has occurred.
- Published
- 2009
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11. Transferable capacity for gastrointestinal colonization in Enterococcus faecium in a mouse model.
- Author
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Rice LB, Lakticová V, Carias LL, Rudin S, Hutton R, and Marshall SH
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- Animals, Anti-Bacterial Agents pharmacology, Bacterial Proteins genetics, Bacterial Proteins metabolism, Disease Models, Animal, Drug Resistance, Bacterial genetics, Enterococcus faecium drug effects, Enterococcus faecium genetics, Female, Gene Expression Regulation, Bacterial, Genes, Bacterial, Mice, Microbial Sensitivity Tests, Selection, Genetic, Vancomycin pharmacology, Enterococcus faecium physiology, Gastrointestinal Diseases microbiology, Gene Transfer, Horizontal, Gram-Positive Bacterial Infections microbiology
- Abstract
A high level of gastrointestinal colonization frequently precedes invasive infection due to Enterococcus faecium. Factors other than antimicrobial resistance that promote gastrointestinal colonization by E. faecium have not been identified. We tested the ability of a colonization-proficient clinical E. faecium isolate (C68) to transfer colonizing ability to noncolonizing E. faecium recipient strains. Transconjugants derived from matings that used E. faecium D344SRF as a recipient strain colonized mouse gastrointestinal tracts in high numbers under selective pressure from clindamycin or vancomycin, compared with control strains that lacked DNA transferred from C68. We transferred DNA into a second recipient strain (E. faecium GE-1), which also colonized mice in significantly greater numbers under selective pressure from clindamycin, compared with a control strain. These results indicate that E. faecium clinical isolates express transmissible factors other than antimicrobial resistance that promote colonization of the mouse gastrointestinal tract.
- Published
- 2009
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12. Impact of short-course quinolone therapy on susceptible and resistant populations of Staphylococcus aureus.
- Author
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Drusano GL, Liu W, Brown DL, Rice LB, and Louie A
- Subjects
- Colony Count, Microbial, Dose-Response Relationship, Drug, Drug Administration Schedule, Humans, Microbial Sensitivity Tests, Models, Biological, Staphylococcal Infections microbiology, Treatment Outcome, Drug Resistance, Bacterial, Fluoroquinolones administration & dosage, Fluoroquinolones pharmacology, Fluoroquinolones therapeutic use, Quinolones administration & dosage, Quinolones pharmacology, Quinolones therapeutic use, Staphylococcal Infections drug therapy, Staphylococcus aureus drug effects, Staphylococcus aureus growth & development
- Abstract
We previously demonstrated that therapy duration has a differential impact on susceptible and resistant subpopulations of Staphylococcus aureus. What our previous investigation did not address was what would transpire after stopping therapy and whether these events would be different in susceptible and resistant subpopulations. We used the regimen previously demonstrated to amplify resistant subpopulation at day 4-5 (area under the concentration-time curve/minimum inhibitory concentration ratio, 100). Therapy was started in our hollow-fiber infection model on day 0; garenoxacin was administered in 4, 5, or 6 doses (days 3-5). The system was observed until day 13. Four drug doses kept the susceptible population dominant, but with the resistant subpopulation amplifying. Five and 6 doses caused the resistant population to exceed the susceptible population at the end of therapy and for a variable time thereafter. Ultimately, the susceptible population became dominant by day 13. Modeling demonstrated that the resistant isolates grew more slowly and had a higher natural death rate.
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- 2009
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13. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America.
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Boucher HW, Talbot GH, Bradley JS, Edwards JE, Gilbert D, Rice LB, Scheld M, Spellberg B, and Bartlett J
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- Humans, United States, Anti-Bacterial Agents pharmacology, Anti-Bacterial Agents therapeutic use, Bacteria drug effects, Bacterial Infections drug therapy, Drug Discovery trends, Drug Resistance, Bacterial
- Abstract
The Infectious Diseases Society of America (IDSA) continues to view with concern the lean pipeline for novel therapeutics to treat drug-resistant infections, especially those caused by gram-negative pathogens. Infections now occur that are resistant to all current antibacterial options. Although the IDSA is encouraged by the prospect of success for some agents currently in preclinical development, there is an urgent, immediate need for new agents with activity against these panresistant organisms. There is no evidence that this need will be met in the foreseeable future. Furthermore, we remain concerned that the infrastructure for discovering and developing new antibacterials continues to stagnate, thereby risking the future pipeline of antibacterial drugs. The IDSA proposed solutions in its 2004 policy report, "Bad Bugs, No Drugs: As Antibiotic R&D Stagnates, a Public Health Crisis Brews," and recently issued a "Call to Action" to provide an update on the scope of the problem and the proposed solutions. A primary objective of these periodic reports is to encourage a community and legislative response to establish greater financial parity between the antimicrobial development and the development of other drugs. Although recent actions of the Food and Drug Administration and the 110th US Congress present a glimmer of hope, significant uncertainly remains. Now, more than ever, it is essential to create a robust and sustainable antibacterial research and development infrastructure--one that can respond to current antibacterial resistance now and anticipate evolving resistance. This challenge requires that industry, academia, the National Institutes of Health, the Food and Drug Administration, the Centers for Disease Control and Prevention, the US Department of Defense, and the new Biomedical Advanced Research and Development Authority at the Department of Health and Human Services work productively together. This report provides an update on potentially effective antibacterial drugs in the late-stage development pipeline, in the hope of encouraging such collaborative action.
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- 2009
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14. Federal funding for the study of antimicrobial resistance in nosocomial pathogens: no ESKAPE.
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Rice LB
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- Anti-Bacterial Agents therapeutic use, Bacterial Infections drug therapy, Cross Infection drug therapy, Humans, National Institute of Allergy and Infectious Diseases (U.S.), Public Health, United States, Anti-Bacterial Agents economics, Bacterial Infections economics, Cross Infection economics, Drug Resistance, Bacterial, Financing, Government
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- 2008
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15. The Maxwell Finland Lecture: for the duration-rational antibiotic administration in an era of antimicrobial resistance and clostridium difficile.
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Rice LB
- Subjects
- Humans, Anti-Bacterial Agents administration & dosage, Anti-Bacterial Agents therapeutic use, Bacterial Infections drug therapy, Bacterial Infections microbiology, Drug Resistance, Bacterial drug effects
- Abstract
Antimicrobial resistance is frequently associated with clinical use of antibiotics. This close association suggests that efforts to manage our use of these potent agents can have an impact on the prevalence of resistance. Unfortunately, one size does not fit all when considering the response of bacterial pathogens to antimicrobial exposure. Measures that may prevent resistance in some species (such as using multiple antibiotics to treat tuberculosis) may exacerbate the problem of resistance in others (such as Pseudomonas aeruginosa or Acinetobacter baumannii). The simplest approach is to use fewer antibiotics and thereby apply less selective pressure to the prevalent flora. Among available strategies to reduce use, reductions in length of antimicrobial regimens are the safest and are likely to be the most palatable to practicing clinicians. Studies are urgently needed to define minimal lengths of therapy to ensure that efforts at reduced use are safe and effective.
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- 2008
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16. Challenges in identifying new antimicrobial agents effective for treating infections with Acinetobacter baumannii and Pseudomonas aeruginosa.
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Rice LB
- Subjects
- Acinetobacter baumannii drug effects, Anti-Infective Agents therapeutic use, Biofilms drug effects, Carbapenems pharmacology, Clinical Trials as Topic, Doripenem, Drug Resistance, Multiple, Bacterial genetics, Humans, Immunocompromised Host drug effects, Minocycline analogs & derivatives, Minocycline therapeutic use, Pseudomonas aeruginosa drug effects, Tigecycline, Acinetobacter Infections drug therapy, Anti-Infective Agents administration & dosage, Carbapenems administration & dosage, Pseudomonas Infections drug therapy
- Abstract
Acinetobacter baumannii and Pseudomonas aeruginosa are gram-negative pathogens that target immunocompromised patients. They express a variety of determinants that confer resistance to a broad array of antimicrobial agents. Mechanisms of resistance include impaired entry through the bacterial outer membrane, production of antibiotic-modifying enzymes, active efflux, and target mutations that reduce antimicrobial affinity. It has been a challenge to identify new agents that have activity against the more resistant variants of these species. Doripenem is a carbapenem in phase 3 trials that has excellent activity against P. aeruginosa and A. baumannii. However, it lacks activity against strains that express resistance to the currently available carbapenems. Tigecycline is a newly licensed glycylcycline that lacks activity against P. aeruginosa but has encouraging activity against many A. baumannii isolates. Resistance to tigecycline can emerge during therapy, however, and is due to expression of multidrug efflux pumps.
- Published
- 2006
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17. In vitro antienterococcal activity explains associations between exposures to antimicrobial agents and risk of colonization by multiresistant enterococci.
- Author
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Rice LB, Lakticová V, Helfand MS, and Hutton-Thomas R
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- Animals, Ceftriaxone administration & dosage, Colony Count, Microbial, Disease Models, Animal, Dose-Response Relationship, Drug, Drug Resistance, Multiple, Bacterial, Feces microbiology, Female, Gastrointestinal Tract microbiology, Gram-Positive Bacterial Infections prevention & control, Mice, Penicillanic Acid administration & dosage, Penicillanic Acid analogs & derivatives, Piperacillin administration & dosage, Piperacillin, Tazobactam Drug Combination, Anti-Bacterial Agents pharmacology, Carrier State prevention & control, Ceftriaxone pharmacology, Enterococcus faecium drug effects, Penicillanic Acid pharmacology, Piperacillin pharmacology
- Abstract
We compared ceftriaxone and piperacillin-tazobactam at doses ranging from 0.1 to 2 times the human equivalent daily dose (HEDD), to determine their impact on gastrointestinal colonization by ampicillin- and vancomycin-resistant Enterococcus faecium C68 in a mouse model. Ceftriaxone failed to promote colonization at doses up to 0.25 times the HEDD, whereas piperacillin-tazobactam promoted colonization at doses up to 0.5 times the HEDD. Ceftriaxone promoted colonization at doses at least 0.5 times the HEDD, whereas piperacillin-tazobactam inhibited colonization at doses at least 0.75 times the HEDD. Both piperacillin-tazobactam and ceftriaxone inhibited colonization by an enterococcal strain devoid of low-affinity penicillin-binding protein-5 (significantly increasing its susceptibility to these agents), at doses that promoted colonization by E. faecium C68. These results support a model in which the impact that different beta -lactam agents have on colonization by VRE is related to the level of the beta -lactam agent's intrinsic antienterococcal activity against the colonizing strain.
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- 2004
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18. Antibiotic therapy for Klebsiella pneumoniae bacteremia: implications of production of extended-spectrum beta-lactamases.
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Paterson DL, Ko WC, Von Gottberg A, Mohapatra S, Casellas JM, Goossens H, Mulazimoglu L, Trenholme G, Klugman KP, Bonomo RA, Rice LB, Wagener MM, McCormack JG, and Yu VL
- Subjects
- Anti-Bacterial Agents therapeutic use, Bacteremia drug therapy, Bacteremia mortality, Drug Resistance, Bacterial, Drug Utilization, Female, Humans, Imipenem pharmacology, Imipenem therapeutic use, Klebsiella Infections drug therapy, Klebsiella Infections mortality, Klebsiella pneumoniae enzymology, Male, Multivariate Analysis, Anti-Bacterial Agents pharmacology, Klebsiella pneumoniae drug effects, beta-Lactam Resistance physiology, beta-Lactamases metabolism
- Abstract
The prevalence of extended-spectrum beta -lactamase (ESBL) production by Klebsiella pneumonia approaches 50% in some countries, with particularly high rates in eastern Europe and Latin America. No randomized trials have ever been performed on treatment of bacteremia due to ESBL-producing organisms; existing data comes only from retrospective, single-institution studies. In a prospective study of 455 consecutive episodes of Klebsiella pneumoniae bacteremia in 12 hospitals in 7 countries, 85 episodes were due to an ESBL-producing organism. Failure to use an antibiotic active against ESBL-producing K. pneumoniae was associated with extremely high mortality. Use of a carbapenem (primarily imipenem) was associated with a significantly lower 14-day mortality than was use of other antibiotics active in vitro. Multivariate analysis including other predictors of mortality showed that use of a carbapenem during the 5-day period after onset of bacteremia due to an ESBL-producing organism was independently associated with lower mortality. Antibiotic choice is particularly important in seriously ill patients with infections due to ESBL-producing K. pneumoniae.
- Published
- 2004
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19. Beta-lactam antibiotics and gastrointestinal colonization with vancomycin-resistant enterococci.
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Rice LB, Hutton-Thomas R, Lakticova V, Helfand MS, and Donskey CJ
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- Animals, Anti-Bacterial Agents pharmacokinetics, Bile metabolism, Female, Mice, Anti-Bacterial Agents pharmacology, Digestive System microbiology, Enterococcus faecium drug effects, Vancomycin Resistance, beta-Lactams pharmacology
- Abstract
We studied the effect of different subcutaneously administered beta-lactam antibiotics on the establishment of gastrointestinal colonization by vancomycin-resistant Enterococcus faecium C68 in a mouse model. Aztreonam, cefazolin, cefepime, and, to a lesser extent, ceftazidime, which neither have significant antienterococcal activity nor are secreted into human bile at high concentrations, did not promote significant vancomycin-resistant enterococci (VRE) colonization. Piperacillin-tazobactam, which has antienterococcal activity and is secreted in human bile at high concentrations, inhibited colonization after limited exposure to the inoculum but was associated with progressively increased VRE colony counts in stool samples after repeated exposure to the VRE inoculum. Ceftriaxone and cefotetan, which lack antienterococcal activity but are secreted into human bile at high concentrations, were associated with rapid and high-level colonization. These data suggest that the risk of VRE colonization varies during exposure to different beta-lactam antimicrobial agents and that the risk is related to biliary concentration and antienterococcal activity of the specific beta-lactam.
- Published
- 2004
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20. Empirical antibiotic choice for the seriously ill patient: are minimization of selection of resistant organisms and maximization of individual outcome mutually exclusive?
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Paterson DL and Rice LB
- Subjects
- Communicable Diseases epidemiology, Drug Resistance, Microbial, Drug Utilization, Humans, Intensive Care Units, Treatment Outcome, Anti-Bacterial Agents therapeutic use, Communicable Diseases drug therapy, Critical Illness mortality, Disease Outbreaks
- Abstract
Mortality related to serious infections in intensive care units (ICUs) is highest if empirical therapy is not active against the organism causing the infection. However, excessive empirical therapy undoubtedly contributes to bacterial resistance to antibiotics, in turn potentially contributing to poor patient outcome. We have reviewed 3 strategies that are increasingly practiced to reduce the hazards of broad empirical therapy, while aiming to ensure that empirical therapy is adequate. The most widely practiced strategy is discontinuation or streamlining of empirical therapy when culture results are available. The second approach is to withdraw certain antibiotic classes (most notably, third-generation cephalosporins) from the ICU antibiotic armamentarium. The third strategy employed is antibiotic cycling. Although this has also appeared to be a successful strategy, currently published studies have used historical controls and thus may be subject to significant bias. Computer-assisted antibiotic prescribing in ICUs may supplement or replace such strategies in the future.
- Published
- 2003
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21. A potential virulence gene, hylEfm, predominates in Enterococcus faecium of clinical origin.
- Author
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Rice LB, Carias L, Rudin S, Vael C, Goossens H, Konstabel C, Klare I, Nallapareddy SR, Huang W, and Murray BE
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- Anti-Bacterial Agents pharmacology, Bacterial Proteins genetics, Cross Infection microbiology, Enterococcus faecium drug effects, Enterococcus faecium isolation & purification, Humans, Membrane Proteins genetics, Vancomycin pharmacology, Vancomycin Resistance, Virulence genetics, Enterococcus faecium genetics, Enterococcus faecium pathogenicity, Genes, Bacterial genetics, Hyaluronoglucosaminidase genetics
- Abstract
An open reading frame (hyl(Efm)) with homologies to previously described hyaluronidase genes has been identified in nonstool isolates of Enterococcus faecium. E. faecium isolates (n=577) from diverse sources were screened for the presence of hyl(Efm) and esp(Efm), a putative virulence gene associated with epidemic E. faecium strains. The presence of esp(Efm) was roughly twice that of hyl(Efm), but both were found primarily in vancomycin-resistant E. faecium isolates in nonstool cultures obtained from patients hospitalized in the United States. These data suggest that specific E. faecium strains may be enriched in determinants that make them more likely to cause clinical infections. Differences in the prevalence of these strains may help explain variations in the clinical importance of multiresistant E. faecium across different continents.
- Published
- 2003
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22. Antibiotic-resistant gram-negative organisms in pediatric chronic-care facilities.
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Lidsky K, Hoyen C, Salvator A, Rice LB, and Toltzis P
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- Adolescent, Adult, Child, Child Care, Child, Preschool, Disease Transmission, Infectious, Female, Gram-Negative Bacteria drug effects, Gram-Negative Bacterial Infections epidemiology, Gram-Negative Bacterial Infections transmission, Humans, Male, Risk Factors, Drug Resistance, Bacterial physiology, Gram-Negative Bacteria physiology
- Abstract
This study was designed to define the prevalence of colonization with antibiotic-resistant gram-negative rectal specimens were obtained from subjects residing in 2 pediatric extended-care facilities and were processed to identify gram-negative organisms resistant to ceftazidime, gentamicin, meropenem, and piperacillin-tazobactam. Horizontal transmission was assessed by analyzing all resistant isolates by pulsed-field gel electrophoresis. Forty percent of subjects were colonized with >/=1 resistant bacillus; >60% of organisms were resistant to >/=2 of the antibiotics tested. Colonization was disproportionate among residents with a tracheostomy or other prosthesis. More than 65% of colonized subjects shared 1 organism with another resident, with cross-colonization occurring among both enteric and nonenteric species. Children residing in chronic-care facilities represent a large reservoir for resistant bacilli. Such colonization may be amenable to simple barrier infection-control procedures.
- Published
- 2002
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23. Inhibition of vancomycin-resistant enterococci by an in vitro continuous-flow competitive exclusion culture containing human stool flora.
- Author
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Donskey CJ, Hume ME, Callaway TR, Das SM, Hoyen CK, and Rice LB
- Subjects
- Anaerobiosis, Bacteriological Techniques, Colony Count, Microbial, Culture Media, Enterococcus faecium drug effects, Humans, Antibiosis, Bacteria growth & development, Enterococcus faecium growth & development, Feces microbiology, Vancomycin Resistance
- Abstract
An in vitro anaerobic continuous-flow competitive exclusion (CFCE) culture model was used to study the ability of human stool flora to inhibit the growth of vancomycin-resistant (VR) enterococci (VRE). The CFCE culture was established from a stool sample obtained from a healthy adult. When 10(3) or 10(6) cfu/mL of VR Enterococcus faecium were added to the CFCE culture, the VRE were eliminated within 6 or 9 days, respectively. When 10(7) cfu/mL of the CFCE culture was added to a continuous-flow culture that contained 10(7) cfu/mL of VRE, the density of VRE was reduced but not eliminated. These data support the hypothesis that the indigenous intestinal flora inhibit growth of VRE and suggest that CFCE cultures may be a useful means to study interactions between the indigenous flora and VRE.
- Published
- 2001
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24. Bacterial monopolists: the bundling and dissemination of antimicrobial resistance genes in gram-positive bacteria.
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Rice LB
- Subjects
- Conjugation, Genetic, DNA Transposable Elements, Drug Resistance, Multiple genetics, Genes, Bacterial genetics, Gram-Positive Bacteria genetics, DNA, Bacterial genetics, Drug Resistance, Microbial genetics
- Abstract
Antibiotic resistance is the unavoidable result of our placing selective pressure on the microbial community. Advances in molecular biology techniques in the past 2 decades have allowed us to greatly improve our understanding of the mechanisms by which resistance emerges and disseminates among human pathogenic bacteria. Gram-positive bacteria employ a diverse array of elements, including plasmids, transposons, insertion sequences, and bacteriophages, to disseminate resistance. An understanding of these mechanisms and their prevalence can improve our ability to treat clinical infections in hospitalized patients, as well as to predict and control the spread of resistant bacteria in the nosocomial environment.
- Published
- 2000
- Full Text
- View/download PDF
25. Effect of parenteral antibiotic administration on the establishment of colonization with vancomycin-resistant Enterococcus faecium in the mouse gastrointestinal tract.
- Author
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Donskey CJ, Hanrahan JA, Hutton RA, and Rice LB
- Subjects
- Animals, Anti-Bacterial Agents administration & dosage, Ceftriaxone therapeutic use, Clavulanic Acid therapeutic use, Enterococcus faecium pathogenicity, Feces microbiology, Female, Humans, Infusions, Parenteral, Mice, Microbial Sensitivity Tests, Ticarcillin therapeutic use, Anti-Bacterial Agents therapeutic use, Enterococcus faecium drug effects, Enterococcus faecium physiology, Gram-Positive Bacterial Infections drug therapy, Intestinal Mucosa microbiology, Vancomycin Resistance
- Abstract
A mouse model of intestinal colonization with vancomycin-resistant enterococci (VRE) was used to study the effect of different beta-lactam antibiotics on establishment of VRE colonization. A clinical VanB VRE isolate, Enterococcus faecium C68 (102 or 104 cfu), was inoculated by gastric gavage in conjunction with subcutaneous administration of antibiotics. The MIC of ceftriaxone and ticarcillin against VRE strain C68 is >10,000 microg/mL, and the MIC of piperacillin is 1250 microg/mL. Ceftriaxone and ticarcillin-clavulanate treatment groups developed persistently high levels of stool VRE compared with both the saline and the piperacillin-tazobactam (Pip-Taz) groups (P<.008). The level of stool VRE in the Pip-Taz group did not differ from that for the saline group. Thus, in this mouse model, beta-lactam antibiotics with minimal anti-enterococcal activity promoted establishment of high-level VRE colonization, but Pip-Taz (a beta-lactam antibiotic with more potent activity against VRE) did not.
- Published
- 2000
- Full Text
- View/download PDF
26. A polyclonal outbreak of predominantly VanB vancomycin-resistant enterococci in northeast Ohio. Northeast Ohio Vancomycin-Resistant Enterococcus Surveillance Program.
- Author
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Donskey CJ, Schreiber JR, Jacobs MR, Shekar R, Salata RA, Gordon S, Whalen CC, Smith F, and Rice LB
- Subjects
- Electrophoresis, Gel, Pulsed-Field, Enterococcus isolation & purification, Feces microbiology, Gram-Positive Bacterial Infections genetics, Humans, Microbial Sensitivity Tests, Molecular Epidemiology, Ohio epidemiology, Prevalence, Disease Outbreaks, Enterococcus genetics, Gram-Positive Bacterial Infections epidemiology, Gram-Positive Bacterial Infections microbiology, Vancomycin Resistance
- Abstract
We studied the molecular epidemiology of vancomycin-resistant enterococci (VRE) isolated in northeast Ohio during 1996 and examined the association between isolation of VRE from samples other than stool and antimicrobial purchases for five Cleveland hospitals. Susceptibility testing and pulsed-field gel electrophoresis were used to analyze 363 isolates from individual patients from 13 hospitals. Susceptibility testing indicated that 287 strains (79%) expressed the VanB phenotype and 76 (21%) expressed the VanA phenotype. The outbreak was polyclonal, with 30 total genotypes. Both VanA and VanB VRE demonstrated multiple genotypes. One genotype was present in all hospitals, suggesting spread between hospitals. For five teaching hospitals, rates of isolation from non-stool sources and from blood correlated positively with purchases of ticarcillin/clavulanic acid (P = .005). In summary, this outbreak demonstrates transmission of VRE between several hospitals in a geographic region and suggests that use of certain beta-lactam antibiotics may be associated with an increased prevalence of VRE.
- Published
- 1999
- Full Text
- View/download PDF
27. Effect of parenteral antibiotic administration on persistence of vancomycin-resistant Enterococcus faecium in the mouse gastrointestinal tract.
- Author
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Donskey CJ, Hanrahan JA, Hutton RA, and Rice LB
- Subjects
- Animals, Colony Count, Microbial, Drug Resistance, Microbial, Enterococcus faecium growth & development, Enterococcus faecium isolation & purification, Feces microbiology, Female, Humans, Injections, Subcutaneous, Mice, Vancomycin administration & dosage, Anti-Bacterial Agents administration & dosage, Anti-Bacterial Agents pharmacology, Digestive System microbiology, Enterococcus faecium drug effects, Vancomycin pharmacology
- Abstract
A mouse model of vancomycin-resistant Enterococcus faecium (VRE) intestinal colonization was used to study the effect of different subcutaneous antibiotics on persistence and density of VRE colonization. Gastric inoculation of a clinical VanB VRE isolate, in conjunction with oral vancomycin in drinking water (250 microgram/mL), resulted in high-level VRE colonization (mean, 9.5 log10 cfu/g) in all 169 experimental mice. After discontinuation of oral vancomycin, the level of VRE in the stool specimens of mice receiving subcutaneous saline steadily decreased (mean, 3.59 log10 cfu/g at day 19). Subcutaneous vancomycin, clindamycin, piperacillin-tazobactam, ticarcillin-clavulanic acid, metronidazole, cefotetan, ampicillin, and ampicillin-sulbactam all promoted persistent high levels of stool VRE. Subcutaneous ceftriaxone, cefepime, ciprofloxacin, and aztreonam promoted increased VRE density to a lesser degree or not at all. Thus, in a mouse model, vancomycin and antibiotics with potent antianaerobic activity promoted persistent high-density intestinal VRE colonization, whereas antibiotics lacking potent antianaerobic activity did not.
- Published
- 1999
- Full Text
- View/download PDF
28. A silver bullet for colonization and infection with methicillin-resistant Staphylococcus aureus still eludes us.
- Author
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Rice LB
- Subjects
- Acinetobacter drug effects, Ceftazidime pharmacology, Ceftazidime therapeutic use, Drug Resistance, Microbial, Drug Therapy, Combination therapeutic use, Formularies, Hospital as Topic, Humans, Anti-Bacterial Agents therapeutic use, Klebsiella Infections drug therapy, Klebsiella pneumoniae drug effects, Methicillin Resistance, Staphylococcal Infections drug therapy, Staphylococcus aureus drug effects
- Published
- 1999
- Full Text
- View/download PDF
29. Ceftazidime-resistant Klebsiella pneumoniae isolates recovered at the Cleveland Department of Veterans Affairs Medical Center.
- Author
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Rice LB, Eckstein EC, DeVente J, and Shlaes DM
- Subjects
- Cross Infection drug therapy, Cross Infection epidemiology, Cross Infection microbiology, Disease Outbreaks, Drug Resistance, Microbial genetics, Electrophoresis, Gel, Pulsed-Field, Hospitals, Veterans, Humans, Klebsiella Infections drug therapy, Klebsiella Infections epidemiology, Klebsiella Infections microbiology, Klebsiella pneumoniae genetics, Molecular Epidemiology, Ohio epidemiology, Plasmids genetics, Plasmids isolation & purification, Ceftazidime pharmacology, Cephalosporins pharmacology, Klebsiella pneumoniae drug effects, Klebsiella pneumoniae isolation & purification
- Abstract
The rate of ceftazidime resistance among Klebsiella pneumoniae isolates recovered from patients at the Cleveland Department of Veterans Affairs Medical Center increased from 6% in the first quarter of 1993 to 28% in the first quarter of 1994. The outbreak was hospitalwide, with the highest rates of resistance occurring on wards where ceftazidime was administered most frequently. Although many plasmid patterns were observed in the clinical isolates, molecular epidemiological analysis with use of pulsed field gel electrophoresis revealed substantial similarities between the strains; this finding suggested that most of the strains-if not all of them-were derived from the original clone. The addition of piperacillin/tazobactam to the hospital formulary and educational efforts focused on minimizing the administration of ceftazidime were associated with a marked decrease in the drug's use and a concomitant decrease in the percentage of ceftazidime-resistant isolates. We have not yet observed a significant rise in the rate of resistance to piperacillin/tazobactam among clinical isolates of K. pneumoniae.
- Published
- 1996
- Full Text
- View/download PDF
30. Molecular genetics of resistance to both ceftazidime and beta-lactam-beta-lactamase inhibitor combinations in Klebsiella pneumoniae and in vivo response to beta-lactam therapy.
- Author
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Rice LB, Carias LL, Bonomo RA, and Shlaes DM
- Subjects
- Abdominal Abscess drug therapy, Amino Acid Sequence, Ampicillin pharmacology, Animals, Base Sequence, DNA, Bacterial analysis, Escherichia coli drug effects, Escherichia coli genetics, Escherichia coli metabolism, Klebsiella Infections drug therapy, Klebsiella pneumoniae drug effects, Klebsiella pneumoniae metabolism, Molecular Biology, Molecular Sequence Data, Penicillanic Acid analogs & derivatives, Penicillanic Acid pharmacology, Piperacillin pharmacology, Piperacillin, Tazobactam Drug Combination, R Factors chemistry, Rats, Sulbactam pharmacology, beta-Lactamases biosynthesis, beta-Lactamases genetics, Ceftazidime pharmacology, Cephalosporin Resistance genetics, Cephalosporins pharmacology, Drug Therapy, Combination pharmacology, Klebsiella pneumoniae genetics, Penicillin Resistance genetics, beta-Lactamase Inhibitors
- Abstract
The molecular basis of ceftazidime resistance in 2 isolates of Klebsiella pneumoniae was studied. The first (21300) expressed resistance to ceftazidime and piperacillin-tazobactam. The second (26139) expressed resistance to ceftazidime but remained susceptible to piperacillin-tazobactam. The 2 strains harbored similar large plasmids that hybridized to TEM- and SHV-related beta-lactamase genes. An Escherichia coli strain harboring the plasmid conferring resistance to both compounds (pLRM7) produced beta-lactamases of pI 5.9 (TEM-6) and pI 7.6 (SHV-1). E. coli harboring the other plasmid (pLRM8) expressed only the TEM enzyme because of insertion of IS15 within blaSHV-1. In vivo studies suggested that resistance to beta-lactam-beta-lactamase inhibitor combinations conferred by pLRM7 will be clinically important. Clinical resistance to both extended-spectrum cephalosporins and beta-lactam-beta-lactamase inhibitor combinations is achievable via the production of two enzymes, with only one possessing an extended spectrum of activity.
- Published
- 1996
- Full Text
- View/download PDF
31. Emerging antimicrobial resistance and the immunocompromised host.
- Author
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Shlaes DM, Binczewski B, and Rice LB
- Subjects
- Aminoglycosides, Anti-Bacterial Agents pharmacology, Anti-Infective Agents pharmacology, Enterococcus drug effects, Fluoroquinolones, Humans, Lactams, Staphylococcus drug effects, Teicoplanin pharmacology, Vancomycin pharmacology, Drug Resistance, Microbial, Gram-Positive Bacterial Infections drug therapy, Immunocompromised Host
- Abstract
Infections caused by gram-positive bacteria have become the most important cause of infectious morbidity among some groups of immunocompromised patients over the last decade. Among the gram-positive bacteria, the emerging problems of resistance to antimicrobial agents include the development of resistance to beta-lactam and aminoglycoside drugs among the enterococci, making synergistic bactericidal therapy impossible; the continued spread of methicillin-resistant staphylococci; resistance to both vancomycin and teicoplanin among enterococci and staphylococci; the emergence of intrinsically vancomycin-resistant species as important pathogens; and resistance to the fluoroquinolones. It is unlikely that new therapeutic classes of antibacterial drugs will be released this decade. Therapeutic alternatives now include unusual combinations of antibiotics to which the strains may appear resistant but that exhibit synergistic activity, although this area has not yet been thoroughly explored. Therefore, control of emergence and spread of resistance through the more judicious use of existing agents, good infection control practices, and the use of imaginative combination therapy for those infected with resistant strains seem to be our best alternatives.
- Published
- 1993
- Full Text
- View/download PDF
32. Evidence for clonal spread of a single strain of beta-lactamase-producing Enterococcus (Streptococcus) faecalis to six hospitals in five states.
- Author
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Murray BE, Singh KV, Markowitz SM, Lopardo HA, Patterson JE, Zervos MJ, Rubeglio E, Eliopoulos GM, Rice LB, and Goldstein FW
- Subjects
- Argentina, Boston, Connecticut, Delaware, Electrophoresis, Agar Gel, Enterococcus faecalis enzymology, Enterococcus faecalis genetics, Florida, Humans, Lebanon, Nucleic Acid Hybridization, Pennsylvania, Philadelphia, Plasmids, Restriction Mapping, Streptococcal Infections transmission, Texas, Virginia, DNA, Bacterial analysis, Enterococcus faecalis classification, Streptococcal Infections microbiology, beta-Lactamases biosynthesis
- Abstract
Beta-lactamase-producing (Bla+) enterococci have been reported in three state and two countries. Pulsed-field gel electrophoresis was used to compare 14 Bla+ Enterococcus (Streptococcus) faecalis isolated from hospitalized patients in seven states and three continents. The restriction endonuclease digestion patterns of isolates from Connecticut, Massachusetts, Lebanon, and Argentina were all markedly different, indicating that these were different strains. However, isolates from Delaware, Texas, Pennsylvania (Philadelphia and Pittsburgh), Florida, and Virginia were similar, indicating that these isolates were derivatives of a single strain. This conclusion was supported by hybridization using individual fragments as probes. Spread of Bla+ enterococci within the hospital setting was also demonstrated. These findings illustrate the value of pulsed-field gel electrophoresis for epidemiologic analyses and support the importance of identifying and containing organisms with new resistance properties in an effort to decrease their transmission to and from, as well as within, hospitals.
- Published
- 1991
- Full Text
- View/download PDF
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