scispace - formally typeset
Search or ask a question
Journal ArticleDOI

Fluoroquinolone resistance among Gram-positive cocci.

01 Sep 2002-Lancet Infectious Diseases (Elsevier)-Vol. 2, Iss: 9, pp 530-538
TL;DR: In this article, the authors highlighted the importance of careful use of these agents in appropriate patients and doses, as well as careful infection-control practices, and emphasized the utility of a valuable class of antimicrobial agents.
Abstract: Summary Resistance to fluoroquinolones among Gram-positive cocci has emerged as these antimicrobial agents have become extensively used in clinical medicine. Resistance is effected by changes in the bacterial target enzymes DNA gyrase and topoisomerase IV, which reduce drug binding, and by action of native bacterial membrane pumps that remove drug from the cell. In both cases, quinolone exposure selects for spontaneous mutants that are present in large bacterial populations, and which contain chromosomal mutations that alter the target protein or increase the level of pump expression. Resistance among clinical isolates has been greatest in Staphylococcus aureus and particularly among meticillinresistant strains, in which both selection by quinolone exposure and transmission of clonal strains in health-care settings have contributed to high prevalence. Resistance in Streptococcus pneumoniae has also emerged in the community. Fluoroquinolone resistance has arisen in multidrug-resistant clones and its prevalence has been especially high in Hong Kong and Spain. Further spread and selection of such resistance could compromise the utility of a valuable class of antimicrobial agents, a point that emphasises the importance of the careful use of these agents in appropriate patients and doses, as well as careful infection-control practices.
Citations
More filters
Journal ArticleDOI
TL;DR: Outpatient antibiotic use in 26 countries in Europe between Jan 1, 1997, and Dec 31, 2002 was investigated by calculating the number of defined daily doses (DDD) per 1000 inhabitants per day according to WHO anatomic therapeutic chemical classification and DDD measurement methodology, and the ecological association between antibiotic use and antibiotic resistance rates was assessed using Spearman's correlation coefficients.

2,894 citations

Journal ArticleDOI
TL;DR: This chapter will describe in detail the major mechanisms of antibiotic resistance encountered in clinical practice, providing specific examples in relevant bacterial pathogens.
Abstract: The discovery, commercialization, and routine administration of antimicrobial compounds to treat infections revolutionized modern medicine and changed the therapeutic paradigm. Indeed, antibiotics have become one of the most important medical interventions needed for the development of complex medical approaches such as cutting-edge surgical procedures, solid organ transplantation, and management of patients with cancer, among others. Unfortunately, the marked increase in antimicrobial resistance among common bacterial pathogens is now threatening this therapeutic accomplishment, jeopardizing the successful outcomes of critically ill patients. In fact, the World Health Organization has named antibiotic resistance as one of the three most important public health threats of the 21st century ( 1 ).

1,429 citations

Journal ArticleDOI
TL;DR: This review will focus on the emergence of antimicrobial resistance in S. aureus, the leading overall cause of nosocomial infections and, as more patients are treated outside the hospital setting, is an increasing concern in the community.
Abstract: In the early 1970s, physicians were finally forced to abandon their belief that, given the vast array of effective antimicrobial agents, virtually all bacterial infections were treatable. Their optimism was shaken by the emergence of resistance to multiple antibiotics among such pathogens as Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Mycobacterium tuberculosis. The evolution of increasingly antimicrobial-resistant bacterial species stems from a multitude of factors that includes the widespread and sometimes inappropriate use of antimicrobials, the extensive use of these agents as growth enhancers in animal feed, and, with the increase in regional and international travel, the relative ease with which antimicrobial-resistant bacteria cross geographic barriers (1–3). The irony of this trend toward progressively more resistant bacteria is that it coincides with a period of dramatically increased understanding of the molecular mechanisms of antimicrobial resistance. Unfortunately, while this insight has resulted in the identification of novel drug targets, it has not yet resulted in effective new chemotherapeutic agents. This paradox stands in sharp contrast to the dramatic progress made in antiviral (notably antiretroviral) therapy in the past ten years, where a number of newly discovered molecular targets have resulted in clinically effective therapeutic agents. Nowhere has this issue been of greater concern than with the Gram-positive bacteria pneumococci, enterococci, and staphylococci. Multidrug resistance is now the norm among these pathogens. S. aureus is perhaps the pathogen of greatest concern because of its intrinsic virulence, its ability to cause a diverse array of life-threatening infections, and its capacity to adapt to different environmental conditions (4, 5). The mortality of S. aureus bacteremia remains approximately 20–40% despite the availability of effective antimicrobials (6). S. aureus is now the leading overall cause of nosocomial infections and, as more patients are treated outside the hospital setting, is an increasing concern in the community (7, 8). S. aureus isolates from intensive care units across the country and from blood culture isolates worldwide are increasingly resistant to a greater number of antimicrobial agents (4, 8). Inevitably this has left fewer effective bactericidal antibiotics to treat these often life-threatening infections (Figure ​(Figure1).1). As rapidly as new antibiotics are introduced, staphylococci have developed efficient mechanisms to neutralize them (Table ​(Table11). Figure 1 S. aureus infections in intensive care units in the National Nosocomial Infections Surveillance System. Data include the total number of infections from 1987 to 1997. Isolates were tested for sensitivity to the following antimicrobial agents: gentamicin, ... Table 1 Mechanisms of S. aureus resistance to antimicrobialsA Recent reports of S. aureus isolates with intermediate or complete resistance to vancomycin portend a chemotherapeutic era in which effective bactericidal antibiotics against this organism may no longer be readily available (9, 10). This review will focus on the emergence of antimicrobial resistance in S. aureus. It will review the historical evolution of resistant strains, their spread, the molecular mechanisms of resistance for selected antibiotics, and progress toward the development of alternative drug targets or novel approaches for therapeutic or prophylactic intervention.

1,382 citations

Journal ArticleDOI
01 Jan 2004-Drugs
TL;DR: Fluoroquinolones and β-lactams of the latest generations are likely to select for overproduction mutants of these pumps and make the bacteria resistant in one step to practically all classes of antibacterial agents.
Abstract: Drug efflux pumps play a key role in drug resistance and also serve other functions in bacteria. There has been a growing list of multidrug and drug-specific efflux pumps characterized from bacteria of human, animal, plant and environmental origins. These pumps are mostly encoded on the chromosome, although they can also be plasmid-encoded. A previous article in this journal provided a comprehensive review regarding efflux-mediated drug resistance in bacteria. In the past 5 years, significant progress has been achieved in further understanding of drug resistance-related efflux transporters and this review focuses on the latest studies in this field since 2003. This has been demonstrated in multiple aspects that include but are not limited to: further molecular and biochemical characterization of the known drug efflux pumps and identification of novel drug efflux pumps; structural elucidation of the transport mechanisms of drug transporters; regulatory mechanisms of drug efflux pumps; determining the role of the drug efflux pumps in other functions such as stress responses, virulence and cell communication; and development of efflux pump inhibitors. Overall, the multifaceted implications of drug efflux transporters warrant novel strategies to combat multidrug resistance in bacteria.

1,118 citations

Journal ArticleDOI
TL;DR: The ESAC project established for the first time a credible alternative to industry sources for the collection of internationally comparable data on antibiotic use in Europe, based on cooperation between regulatory authorities, scientific societies, health insurers and professional organizations.
Abstract: Background: Data on more than a decade of outpatient quinolone use were collected from 33 European countries within the European Surveillance of Antimicrobial Consumption (ESAC) project, funded by the European Centre for Disease Prevention and Control (ECDC). Methods: For the period 1997– 2009, data on outpatient use of systemic quinolones aggregated at the level of the active substance were collected using the Anatomical Therapeutic Chemical (ATC)/defined daily dose (DDD) method (WHO, version 2011), and expressed in DDD and packages per 1000 inhabitants per day (DID and PID, respectively). Using a classification based on pharmacokinetic and in vitro potency profiles, quinolone use was analysed with regard to trends over time, seasonal variation and composition. Results: Total outpatient quinolone use in 2009 varied by a factor of 7.5 between the country with the highest (Italy, 3.61 DID) and the country with the lowest (the UK, 0.48 DID) quinolone use. The second-generation quinolones accounted for .50% of quinolone use (mainly ciprofloxacin), except for Croatia, where first-generation quinolones (mainly norfloxacin) were mostly used. A significant increase in outpatient quinolone use was found for Europe, as well as a large seasonal variation, which increased significantly over time from 1997 to 2009. Relative use of third-generation quinolones significantly increased over time with respect to the use of second-generation quinolones, while the relative use of both significantly increased with respect to the firstgeneration quinolones. Levofloxacin and moxifloxacin (respiratory quinolones) represented .10% of quinolone outpatient use in 17 countries, with extreme seasonal variation in all countries. Conclusions: There was a substantial increase and change in the pattern of quinolone use between 1997 and 2009, a period during which quinolones that are effective for the treatment of respiratory tract infections were introduced. These quinolones are not the first-line antibiotics for this indication and their use should generally be limited, and quinolones should ideally show no substantial seasonal variation in terms of their use.

651 citations

References
More filters
Journal ArticleDOI
TL;DR: The campaign produced a sustained improvement in compliance with hand hygiene, coinciding with a reduction of nosocomial infections and MRSA transmission, and the promotion of bedside, antiseptic handrubs largely contributed to the increase in compliance.

2,404 citations

Journal ArticleDOI
TL;DR: This study highlights the need to understand more fully the role of Epstein-Barr virus in the development of central giant cell granuloma and its role in the immune system.
Abstract: John G. Bartlett,1 Scott F Dowell,2 Lionel A. Mandell,6 Thomas M. File, Jr.,3 Daniel M. Musher,4 and Michael J. Fine5 'Johns Hopkins University School of Medicine, Baltimore, Maryland, 2Centers for Disease Control and Prevention, Atlanta, Georgia, 3Northeastern Ohio Universities College of Medicine, Cleveland, Ohio, 4Baylor College of Medicine and Veterans Affairs Medical Center, Houston, Texas, and 5University of Pittsburgh, Pennsylvania, USA; and 6McMaster University, Toronto, Canada

2,292 citations

Journal ArticleDOI
TL;DR: Quinolone-topoisomerase biology is providing a model for understanding aspects of host-parasite interactions and providing ways to investigate manipulation of the bacterial chromosome by topoisomerases.
Abstract: For many years, DNA gyrase was thought to be responsible both for unlinking replicated daughter chromosomes and for controlling negative superhelical tension in bacterial DNA. However, in 1990 a homolog of gyrase, topoisomerase IV, that had a potent decatenating activity was discovered. It is now clear that topoisomerase IV, rather than gyrase, is responsible for decatenation of interlinked chromosomes. Moreover, topoisomerase IV is a target of the 4-quinolones, antibacterial agents that had previously been thought to target only gyrase. The key event in quinolone action is reversible trapping of gyrase-DNA and topoisomerase IV-DNA complexes. Complex formation with gyrase is followed by a rapid, reversible inhibition of DNA synthesis, cessation of growth, and induction of the SOS response. At higher drug concentrations, cell death occurs as double-strand DNA breaks are released from trapped gyrase and/or topoisomerase IV complexes. Repair of quinolone-induced DNA damage occurs largely via recombination pathways. In many gram-negative bacteria, resistance to moderate levels of quinolone arises from mutation of the gyrase A protein and resistance to high levels of quinolone arises from mutation of a second gyrase and/or topoisomerase IV site. For some gram-positive bacteria, the situation is reversed: primary resistance occurs through changes in topoisomerase IV while gyrase changes give additional resistance. Gyrase is also trapped on DNA by lethal gene products of certain large, low-copy-number plasmids. Thus, quinolone-topoisomerase biology is providing a model for understanding aspects of host-parasite interactions and providing ways to investigate manipulation of the bacterial chromosome by topoisomerases.

1,436 citations

Journal ArticleDOI
TL;DR: Whether the normal physiological role of the multidrug efflux systems is to protect the cell from toxic compounds or whether they fulfil primary functions unrelated to drug resistance and only efflux multiple drugs fortuitously or opportunistically is discussed.

1,117 citations