Article

Appropriate vs. inappropriate antimicrobial therapy

Health Informatics Centre, Division of Community Health Sciences, Dundee, UK.
Clinical Microbiology and Infection (Impact Factor: 5.2). 05/2008; 14 Suppl 3(Suppl 3):15-21. DOI: 10.1111/j.1469-0691.2008.01959.x
Source: PubMed

ABSTRACT Inappropriate antimicrobial treatment (defined as use of antimicrobial agent to which a pathogen is resistant) or a delay in starting appropriate treatment are both associated with increased morbidity and mortality. Studies of ventilator-associated pneumonia, intra-abdominal infections or bacteraemia document higher mortality in patients who received inappropriate therapy. In addition, the outcome in patients switched from inappropriate to appropriate therapy is better than for patients who remained on inappropriate therapy, but the benefit is not as great as for those who were started on appropriate therapy initially. While inappropriate therapy undoubtedly has an important influence on outcomes, it needs to be considered in the context of other patient risk-factors, such as co-morbid conditions, severity score measures, and functional status. When assessing the impact of inappropriate therapy on outcomes such as length of hospital stay, it is important to be as precise as possible about the time of onset of infection. Failure to do so may lead to inaccurate estimation of the effect of inappropriate therapy. While the likelihood that resistant pathogens can increase costs throughout the healthcare system is generally recognised, an under-appreciated aspect of resistance is its consequences for patients and their carers. Initiatives are underway to gauge the impact of resistance and strategies to combat its spread.

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    • "Infections caused by antimicrobial-resistant microorganisms are often associated with poor clinical outcomes, resulting in increased morbidity and mortality. Many factors contribute to the spread of drug-resistant infections, including weak health systems,1,2 failing public health control,3 population movements and international travel of people who may be infected or asymptomatically colonized by resistant strains,4 unregulated use of antibiotics in many parts of the world5 and inappropriate drug use in countries with tighter regulation.4,6 There are also biological factors, including spread of resistant strains and spread of mobile genetic elements, that can transfer resistance genes between strains, species and genera. "
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    ABSTRACT: To assess the level of research funding awarded to UK institutions specifically for antimicrobial resistance-related research and how closely the topics funded relate to the clinical and public health burden of resistance. Databases and web sites were systematically searched for information on how infectious disease research studies were funded for the period 1997-2010. Studies specifically related to antimicrobial resistance, including bacteriology, virology, mycology and parasitology research, were identified and categorized in terms of funding by pathogen and disease and by a research and development value chain describing the type of science. The overall dataset included 6165 studies receiving a total investment of £2.6 billion, of which £102 million was directed towards antimicrobial resistance research (5.5% of total studies, 3.9% of total spend). Of 337 resistance-related projects, 175 studies focused on bacteriology (40.2% of total resistance-related spending), 42 focused on antiviral resistance (17.2% of funding) and 51 focused on parasitology (27.4% of funding). Mean annual funding ranged from £1.9 million in 1997 to £22.1 million in 2009. Despite the fact that the emergence of antimicrobial resistance threatens our future ability to treat many infections, the proportion of the UK infection-research spend targeting this important area is small. There are encouraging signs of increased investment in this area, but it is important that this is sustained and targeted at areas of projected greatest burden. Two areas of particular concern requiring more investment are tuberculosis and multidrug-resistant Gram-negative bacteria.
    Journal of Antimicrobial Chemotherapy 02/2014; 69(2):548-554. DOI:10.1093/jac/dkt349 · 5.44 Impact Factor
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    • "Many factors such as recent exposure to other antimicrobials, multidrug resistance of pathogens, and underlying diseases impose considerably on physicians' decision. Inappropriateness of the administered therapy may have a significant impact on final outcome [2]. As a consequence, it is helpful to use a surrogate marker that can advise for the early need to change administered antimicrobials particularly when culture of biologic specimens are sterile or there is considerable time delay until the antibiogram of the implicated pathogen is available. "
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    ABSTRACT: The objective of this study is to define if early changes of procalcitonin (PCT) may inform about prognosis and appropriateness of administered therapy in sepsis. A prospective multicenter observational study was conducted in 289 patients. Blood samples were drawn on day 1, that is, within less than 24 hours from advent of signs of sepsis, and on days 3, 7, and 10. Procalcitonin was estimated in serum by the ultrasensitive Kryptor assay (BRAHMS GmbH, Hennigsdorf, Germany). Patients were divided into the following 2 groups according to the type of change of PCT: group 1, where PCT on day 3 was decreased by more than 30% or was below 0.25 ng/mL, and group 2, where PCT on day 3 was either increased above 0.25 ng/mL or decreased less than 30%. Death occurred in 12.3% of patients of group 1 and in 29.9% of those of group 2 (P < .0001). Odds ratio for death of patients of group 1 was 0.328. Odds ratio for the administration of inappropriate antimicrobials of patients of group 2 was 2.519 (P = .003). Changes of serum PCT within the first 48 hours reflect the benefit or not of the administered antimicrobial therapy. Serial PCT measurements should be used in clinical practice to guide administration of appropriate antimicrobials.
    Journal of critical care 06/2011; 26(3):331.e1-7. DOI:10.1016/j.jcrc.2010.07.012 · 2.19 Impact Factor
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    • "During the last half decade of the 20th century, several major studies conducted in critically ill patients in both Europe and the USA demonstrated unequivocally that initial inappropriate antimicrobial treatment for pneumonia was associated with increased mortality [1]. It is of note that both in these earlier studies and in subsequent confirmatory ones [2,3], the appropriateness of treatment was typically assessed in terms of antimicrobial coverage, defined as the use of an agent to which a pathogen is susceptible [4]. In contrast, less attention – if any – was given to the fact that failures of anti-infective therapy in the intensive care unit (ICU) setting might occur not only as a consequence of inappropriate choice but also with inappropriate dosing, potentially leading to suboptimal exposure to the broad-spectrum antimicrobial agent at the infection site, even if it is administered in a timely manner [5]. "
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    ABSTRACT: Appropriate antibiotic therapy in patients with severe sepsis and septic shock should mean prompt achievement and maintenance of optimal exposure at the infection site with broad-spectrum antimicrobial agents administered in a timely manner. Once the causative pathogens have been identified and tested for in vitro susceptibility, subsequent de-escalation of antimicrobial therapy should be applied whenever feasible. The goal of appropriate antibiotic therapy must be pursued resolutely and with continuity, in view of the ongoing explosion of antibiotic-resistant infections that plague the intensive care unit setting and of the continued decrease in new antibiotics emerging. This article provides some principles for the correct handling of antimicrobial dosing regimens in patients with severe sepsis and septic shock, in whom various pathophysiological conditions may significantly alter the pharmacokinetic behaviour of drugs.
    Critical care (London, England) 07/2009; 13(3):214. DOI:10.1186/cc7774
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