O. Cars - Academia.edu (original) (raw)

Papers by O. Cars

Journal of Antimicrobial Chemotherapy, 2006

Objectives: To evaluate the mutant prevention concentrations (MPCs) of ciprofloxacin for two susc... more Objectives: To evaluate the mutant prevention concentrations (MPCs) of ciprofloxacin for two susceptible and one first-step gyrA resistant mutant Escherichia coli strains in an in vitro kinetic model and to identify the pharmacodynamic index that best predicts prevention of resistance emergence.

Antibiotic Policies, 2005

Sufficient data on antibiotic use in the community is lacking in most countries. Few countries ca... more Sufficient data on antibiotic use in the community is lacking in most countries. Few countries can show antibiotic use data over time, to analyse trends in prescribing. All countries have an important role to ensure that validated national and regional, data on antibiotic prescribing and sales are made publicly available. The collection of DID data in the ESAC project is

Scandinavian Journal of Infectious Diseases, 2002

The Lancet Infectious Diseases, 2008

Resistance) was therefore started in 1994 to provide surveillance of antibiotic use and resistanc... more Resistance) was therefore started in 1994 to provide surveillance of antibiotic use and resistance, and to implement the rational use of antibiotics and development of new knowledge. Between 1995 and 2004, antibiotic use for outpatients decreased from 15·7 to 12·6 defined daily doses per 1000 inhabitants per day and from 536 to 410 prescriptions per 1000 inhabitants per year. The reduction was most prominent in children aged 5-14 years (52%) and for macrolides (65%). During this period, the number of hospital admissions for acute mastoiditis, rhinosinusitis, and quinsy (peritonsillar abscess) was stable or declining. Although the epidemic spread in southern Sweden of penicillin-resistant Streptococcus pneumoniae was curbed, the national frequency increased from 4% to 6%. Resistance remained low in most other bacterial species during this period. This multidisciplinary, coordinated programme has contributed to the reduction of antibiotic use without measurable negative consequences. However, antibiotic resistance in several bacterial species is slowly increasing, which has led to calls for continued sustained efforts to preserve the effectiveness of available antibiotics.

The Lancet, 2001

Data on antibiotic use are not publicly available in most European Union countries. We obtained d... more Data on antibiotic use are not publicly available in most European Union countries. We obtained data for non-hospital antibiotic sales for 1997 from the 15 member states and analysed these according to the Anatomic Therapeutic Chemical classification system, and expressed them as defined daily doses per 1000 people per day. Sales of antibiotics varied more than four-fold: France (36.5), Spain (32.4), Portugal (28.8), and Belgium (26.7) had the highest sales, whereas the Netherlands (8.9), Denmark (11.3), Sweden (13.5), and Germany (13.6) had the lowest. There was also profound variation in use of different classes of antibiotics. Detailed knowledge of antibiotic use is necessary to implement national strategies for optimum antibiotic use, and to address the threat posed by resistant microorganisms.

Background: Data on actual antimicrobial prescriptions are rarely made available and the World He... more Background: Data on actual antimicrobial prescriptions are rarely made available and the World Health Organization (WHO) recommends using the number of defined daily doses (DDDs) as a measurement unit for inter-country comparisons of antimicrobial use in outpatients. However, because antimicrobials are given for limited periods of time and the DDDs may not represent the doses used in practice, this measurement

Journal of Antimicrobial Chemotherapy, 2008

Objectives: The aim of the present investigation was to study and characterize the effect of vori... more Objectives: The aim of the present investigation was to study and characterize the effect of voriconazole on the fungicidal activity of amphotericin B.

International Journal of Antimicrobial Agents, 2007

Emerging Infectious Diseases, 2002

Drug Resistance Updates, 2011

Antibiotic resistance has emerged as one of the greatest global health challenges to be addressed... more Antibiotic resistance has emerged as one of the greatest global health challenges to be addressed in the 21st Century. The risk of widespread antibiotic resistance threatens to mitigate the positive changes made in modernizing healthcare systems; therefore, fresh approaches are essential, as well as new and effective antibacterial drugs. In a globalized world, a spectrum of different interventions and health technologies must be employed to contain antibiotic resistance. Finding ways of accelerating the development of new drugs and diagnostic tools is one strategy, as is better surveillance of antibiotic resistance and ways of improving use of existing antibiotics. Moreover, a framework to regulate use is called for to avoid that potential new antibiotics are squandered. Finally, the ongoing pandemic spread of resistant bacteria illustrates that the problem can only be addressed through international cooperation and thus that any new strategy to manage antibiotic resistance must take into consideration issues of global access and affordability.

Clinical Microbiology and Infection, 2014

The increasing prevalence of hospital and community-acquired infections caused by multidrug-resis... more The increasing prevalence of hospital and community-acquired infections caused by multidrug-resistant (MDR) bacterial pathogens is rapidly limiting the options for effective antibiotic therapy. Systematic studies on combinations of already available antibiotics that could provide an effective treatment against MDR bacteria are needed. We tested combinations of antibiotics that target one important physiological function (peptidoglycan synthesis) at several steps, and studied Enterobacteriaceae (Klebsiella pneumoniae and Escherichia coli) for which multidrug resistance associated with ESBL-producing plasmids has become a major problem. To measure the effectiveness of antibiotics alone and in combination, we used checkerboard assays, static antibiotic concentration time-kill assays, and an improved in-vitro kinetic model that simulates human pharmacokinetics of multiple simultaneously administered antibiotics. The target strains included an MDR K. pneumoniae isolate responsible for a recent major hospital outbreak. A double combination (fosfomycin and aztreonam) and a triple combination (fosfomycin, aztreonam and mecillinam) were both highly effective in reducing bacterial populations in all assays, including the in vitro kinetic model. These combinations were effective even though each of the MDR strains was resistant to aztreonam alone. Our results provide an initial validation of the potential usefulness of a combination of antibiotics targeting peptidoglycan synthesis in the treatment of MDR Gram-negative bacteria. We suggest that a combination of fosfomycin with aztreonam could become a useful treatment option for such infections and should be further studied.

Clinical Microbiology and Infection, 2007

The aim of this study was to develop and validate a new in-vitro kinetic model for the combinatio... more The aim of this study was to develop and validate a new in-vitro kinetic model for the combination of two drugs with different half-lives, and to use this model for the study of the pharmacodynamic effects of amphotericin B and voriconazole, alone or in combination, against a strain of Candida albicans. Bolus doses of voriconazole and amphotericin B were administered to a starting inoculum of C. albicans. Antifungal-containing medium was eliminated and replaced by fresh medium using a peristaltic pump, with the flow-rate adjusted to obtain the desired half-life of the drug with the shorter half-life. A computer-controlled dosing pump compensated for the agent with the longer half-life. Voriconazole and amphotericin B half-lives were set to 6 and 24 h, respectively. Pharmacokinetic parameters were close to target values when both single doses and sequential doses were simulated. Voriconazole and amphotericin B administered alone demonstrated fungistatic and fungicidal activity, respectively. Simultaneous administration resulted in fungicidal activity, whereas pre-exposure of C. albicans to voriconazole, followed by amphotericin at 8 and 32 h, resulted in fungistatic activity similar to that observed with voriconazole alone. Using this model, which allowed a combination of antifungal agents with different half-lives, it was possible to demonstrate an antagonistic effect of voriconazole on the fungicidal activity of amphotericin B. The characteristics and clinical relevance of this interaction require further investigation.

Clinical Microbiology and Infection, 2002

Growing concern over the spread of resistance to antibiotics and other antimicrobials has prompte... more Growing concern over the spread of resistance to antibiotics and other antimicrobials has prompted a plethora of recommendations for its control. Strategic programs for resistance containment have been initiated in various countries, particularly in Western Europe and North America. The World Health Organization and the European Union have responded to the need for international action by publishing guidance and encouraging collaboration. These recommendations rightly focus on controlling resistance in the community. They agree on the importance of surveillance of resistance patterns and antibiotic usage and the need to encourage judicious antibiotic usage (especially through education of prescribers and the public). Yet there remains a pressing need for the implementation of effective actions to address these issues. Important considerations given less attention include infection prevention (e.g. through immunization), the use of rapid diagnostic tests to reduce antibiotic usage, audit of implemented actions, and the provision of feedback. Furthermore, research is necessary to fill the substantial gaps in our knowledge. Notably, the reversibility or containment of resistance with the optimization of antibiotic usage has yet to be definitely established. For now, antimicrobial management programs should focus on ensuring the most appropriate use of antimicrobials rather than simply on limiting choices. Finally, developed countries must recognize that a truly global approach to resistance containment will require greater support for developing countries.

…, 2009

... enligt rekommendationerna [3, 4]. Till exempel förskrivs antibiotika i dag till cirka 50 proc... more ... enligt rekommendationerna [3, 4]. Till exempel förskrivs antibiotika i dag till cirka 50 procent av alla patienter med hosta och akut ... CHEFREDAKTÖR OCH ANSVARIG UTGIVARE Jonas Hultkvist FAKTURAADRESS Läkartidningen Förlag AB, FE515, PLF1020, 105 69 Stockholm.

BMJ, 1998

ABSTRACT * Is a major threat to public health There is an incoming tide of concern about the prob... more ABSTRACT * Is a major threat to public health There is an incoming tide of concern about the problems of antimicrobial resistance. For several years alarm has been expressed in the United States,1 and the past 12 months have seen two World Health Organisation meetings prompted by increasing anxieties about the role of antimicrobials in animal husbandry2 a report by Britain's House of Lords on antimicrobial resistance; and a report from the US Institute of Medicine on emerging infections.3 This week the Danish Chief Medical Officer, Einar Krag, has called together colleagues from the European Union and their advisors for a conference on “the microbial threat” to “assess the strategies to prevent and control the emergence and spread of antimicrobial resistant micro-organisms.” Is all this activity warranted? We believe it is: in the words of the House of Lords' report, “Resistance to antibiotics … constitutes a major threat to public health and ought to be recognised as such more widely than it is at present.” This issue of the BMJ is helping to broadcast this message. The causes of these problems and gloomy portents are not difficult to find. In the past 50 years people in both the developed and developing worlds have accepted antibiotics as their right — to obtain a prescription at the first sign of a trivial infection or treat themselves with a handful of cheap antibiotics. We cannot conceive a return to the pre-antibiotic days, yet the unbridled use of these agents in man and animals is inexorably propelling us …

Journal of Global Antimicrobial Resistance, 2013