M. de Kraker

Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

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Publications (22)94.56 Total impact

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    ABSTRACT: Background Complicated urinary tract infections (c-UTIs) are among the most common nosocomial infections and a substantial part of the antimicrobial agents used in hospitals is for the treatment of c-UTIs. Data from surveillance can be used to guide the empirical treatment choices of clinicians when treating c-UTIs. We therefore used nation-wide surveillance data to evaluate antimicrobial coverage of agents for the treatment of c-UTI in the Netherlands. Methods We included the first isolate per patient of urine samples of hospitalised patients collected by the Infectious Disease Surveillance Information System for Antibiotic Resistance (ISIS-AR) in 2012, and determined the probability of inadequate coverage for antimicrobial agents based on species distribution and susceptibility. Analyses were repeated for various patient groups and hospital settings. Results The most prevalent bacteria in 27,922 isolates of 23,357 patients were Escherichia coli (47%), Enterococcus spp. (14%), Proteus mirabilis (8%), and Klebsiella pneumoniae (7%). For all species combined, the probability of inadequate coverage was <5% for amoxicillin or amoxicillin-clavulanic acid combined with gentamicin and the carbapenems. When including gram-negative bacteria only, the probability of inadequate coverage was 4.0%, 2.7%, 2.3% and 1.7%, respectively, for amoxicillin, amoxicillin-clavulanic acid, a second or a third generation cephalosporin in combination with gentamicin, and the carbapenems (0.4%). There were only small variations in results among different patient groups and hospital settings. Conclusions When excluding Enterococcus spp., considered as less virulent, and the carbapenems, considered as last-resort drugs, empirical treatment for c-UTI with the best chance of adequate coverage are one of the studied beta-lactam-gentamicin combinations. This study demonstrates the applicability of routine surveillance data for up-to-date clinical practice guidelines on empirical antimicrobial therapy, essential in patient care given the evolving bacterial susceptibility.
    PLoS ONE 01/2014; 9(1):1-7. · 3.53 Impact Factor
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    ABSTRACT: Clin Microbiol Infect ABSTRACT: We investigated bacteraemia trends for five major bacterial pathogens, Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Enterococcus faecalis and Enterococcus faecium, and determined how expanding antimicrobial resistance influenced the total burden of bacteraemias in Europe. Aetiological fractions of species and antibiotic phenotypes were extracted from the European Antimicrobial Resistance Surveillance System (EARSS) database for laboratories, which consistently reported between 2002 and 2008. Trend analyses used generalized linear models. Robustness of results was assessed by iterative analysis for different geographic regions. From 2002 to 2008, the overall number of reports increased annually by 6.4% (95% confidence interval (CI) 6.2-6.5%), from 46 095 to 67 876. In the subset of laboratories providing denominator information, the overall incidence increased from 0.58/1000 patient-days to 0.90/1000 patient-days (7.2% per year; 95% CI 6.9-7.5%). The frequency of reported bacteraemia isolates of S. aureus and Streptococcus pneumoniae increased moderately, while increase in E. coli and Enterococcus faecium was more pronounced. Bacteraemias caused by methicillin-resistant S. aureus increased until 2005 (7.6% per year; 95% CI 6.1-9.1%), and then decreased (-4.8% per year; 95% CI -6.1 to -3.5%), whereas the number attributable to methicillin-sensitive S. aureus increased continuously (3.4% per year; 95% CI 3.0-3.7). Increasing rates of E. coli were mainly caused by antibiotic-resistant phenotypes. Our data suggest that the burden of bacterial bloodstream infection has been increasing for all species during EARSS surveillance. Trends were mainly driven by resistant strains and clearly dissociated between resistant and susceptible isolates. It appears that infections with resistant clones add to rather than replace infections caused by susceptible bacteria. As a consequence, expansion of antibiotic resistance creates an additional strain on healthcare systems.
    Clinical Microbiology and Infection 10/2012; · 4.58 Impact Factor
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    ABSTRACT: Clin Microbiol Infect 2012; 18: E466-E472 ABSTRACT: Dutch laboratories are currently changing their breakpoint criteria from mostly Clinical Laboratory and Standards Institute (CLSI) breakpoints to European Committee on Antimicrobial Susceptibility Testing (EUCAST) breakpoints. To evaluate the impact of these changes, we studied antimicrobial resistance trends of Escherichia coli in blood specimens from January 2008 to January 2012 using CLSI and EUCAST breakpoints and compared them with the antimicrobial susceptibility test (AST) interpretations reported by Dutch laboratories participating in the Infectious Disease Surveillance Information System for Antibiotic Resistance (ISIS-AR). ISIS-AR collects AST interpretations, including underlying minimal inhibitory concentrations (MICs) of routinely cultured bacterial species on a monthly basis from Dutch laboratories. MICs of Etests or automated systems were reinterpreted according to the CLSI 2009 and EUCAST 2010 guidelines. Trends in non-susceptibility (i.e. intermediate resistant and resistant) over time were analysed by the Cochran-Armitage test for trend. The effects of the change from CLSI to EUCAST breakpoints on non-susceptibility were small. There were no differences in non-susceptibility to amoxicillin, amoxicillin/clavulanic acid, cefuroxim, gentamicin and co-trimoxazol and only small differences (1-1.5%) for ciprofloxacin between AST interpretations by CLSI or EUCAST. However, for ceftazidime, and cefotaxime/ceftriaxone the proportion of non-susceptibility was substantially higher when EUCAST breakpoints were used (2-3%). The effects on time trends of the change in guidelines were limited, with only substantial differences for the oxymino-cephalosporins. Our study shows that the implementation of EUCAST breakpoints has a limited effect on the proportion of non-susceptible isolates and time trends in E. coli for most, but not all, antimicrobial agents.
    Clinical Microbiology and Infection 07/2012; 18(11):E466-E472. · 4.58 Impact Factor
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    Marlieke E A de Kraker, Peter G Davey, Hajo Grundmann
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    ABSTRACT: The relative importance of human diseases is conventionally assessed by cause-specific mortality, morbidity, and economic impact. Current estimates for infections caused by antibiotic-resistant bacteria are not sufficiently supported by quantitative empirical data. This study determined the excess number of deaths, bed-days, and hospital costs associated with blood stream infections (BSIs) caused by methicillin-resistant Staphylococcus aureus (MRSA) and third-generation cephalosporin-resistant Escherichia coli (G3CREC) in 31 countries that participated in the European Antimicrobial Resistance Surveillance System (EARSS). The number of BSIs caused by MRSA and G3CREC was extrapolated from EARSS prevalence data and national health care statistics. Prospective cohort studies, carried out in hospitals participating in EARSS in 2007, provided the parameters for estimating the excess 30-d mortality and hospital stay associated with BSIs caused by either MRSA or G3CREC. Hospital expenditure was derived from a publicly available cost model. Trends established by EARSS were used to determine the trajectories for MRSA and G3CREC prevalence until 2015. In 2007, 27,711 episodes of MRSA BSIs were associated with 5,503 excess deaths and 255,683 excess hospital days in the participating countries, whereas 15,183 episodes of G3CREC BSIs were associated with 2,712 excess deaths and 120,065 extra hospital days. The total costs attributable to excess hospital stays for MRSA and G3CREC BSIs were 44.0 and 18.1 million Euros (63.1 and 29.7 million international dollars), respectively. Based on prevailing trends, the number of BSIs caused by G3CREC is likely to rapidly increase, outnumbering the number of MRSA BSIs in the near future. Excess mortality associated with BSIs caused by MRSA and G3CREC is significant, and the prolongation of hospital stay imposes a considerable burden on health care systems. A foreseeable shift in the burden of antibiotic resistance from Gram-positive to Gram-negative infections will exacerbate this situation and is reason for concern.
    PLoS Medicine 10/2011; 8(10):e1001104. · 15.25 Impact Factor
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    ABSTRACT: Antimicrobial resistance is threatening the successful management of nosocomial infections worldwide. Despite the therapeutic limitations imposed by methicillin-resistant Staphylococcus aureus (MRSA), its clinical impact is still debated. The objective of this study was to estimate the excess mortality and length of hospital stay (LOS) associated with MRSA bloodstream infections (BSI) in European hospitals. Between July 2007 and June 2008, a multicenter, prospective, parallel matched-cohort study was carried out in 13 tertiary care hospitals in as many European countries. Cohort I consisted of patients with MRSA BSI and cohort II of patients with methicillin-susceptible S. aureus (MSSA) BSI. The patients in both cohorts were matched for LOS prior to the onset of BSI with patients free of the respective BSI. Cohort I consisted of 248 MRSA patients and 453 controls and cohort II of 618 MSSA patients and 1,170 controls. Compared to the controls, MRSA patients had higher 30-day mortality (adjusted odds ratio [aOR] = 4.4) and higher hospital mortality (adjusted hazard ratio [aHR] = 3.5). Their excess LOS was 9.2 days. MSSA patients also had higher 30-day (aOR = 2.4) and hospital (aHR = 3.1) mortality and an excess LOS of 8.6 days. When the outcomes from the two cohorts were compared, an effect attributable to methicillin resistance was found for 30-day mortality (OR = 1.8; P = 0.04), but not for hospital mortality (HR = 1.1; P = 0.63) or LOS (difference = 0.6 days; P = 0.96). Irrespective of methicillin susceptibility, S. aureus BSI has a significant impact on morbidity and mortality. In addition, MRSA BSI leads to a fatal outcome more frequently than MSSA BSI. Infection control efforts in hospitals should aim to contain infections caused by both resistant and susceptible S. aureus.
    Antimicrobial Agents and Chemotherapy 06/2011; 55(4):1598-605. · 4.57 Impact Factor
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    Hajo Grundmann, Marlieke de Kraker, Peter Davey
    The Lancet Infectious Diseases 05/2011; 11(5):344; author reply 344-5. · 19.97 Impact Factor
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    ABSTRACT: This study determined excess mortality and length of hospital stay (LOS) attributable to bloodstream infection (BSI) caused by third-generation-cephalosporin-resistant Escherichia coli in Europe. A prospective parallel matched cohort design was used. Cohort I consisted of patients with third-generation-cephalosporin-resistant E. coli BSI (REC) and cohort II consisted of patients with third-generation-cephalosporin-susceptible E. coli BSI (SEC). Patients in both cohorts were matched for LOS before infection with patients free of the respective BSI. Thirteen European tertiary care centres participated between July 2007 and June 2008. Cohort I consisted of 111 REC patients and 204 controls and cohort II consisted of 1110 SEC patients and 2084 controls. REC patients had a higher mortality at 30 days (adjusted odds ratio = 4.6) and a higher hospital mortality (adjusted hazard ratio = 5.7) than their controls. LOS was increased by 8 days. For SEC patients, these figures were adjusted odds ratio = 1.9, adjusted hazard ratio = 2.0 and excess LOS = 3 days. A 2.5 times [95% confidence interval (95% CI) 0.9-6.8] increase in all-cause mortality at 30 days and a 2.9 times (95% CI 1.2-6.9) increase in mortality during entire hospital stay as well as an excess LOS of 5 days (95% CI 0.4-10.2) could be attributed to resistance to third-generation cephalosporins in E. coli BSI. Morbidity and mortality attributable to third-generation-cephalosporin-resistant E. coli BSI is significant. If prevailing resistance trends continue, high societal and economic costs can be expected. Better management of infections caused by resistant E. coli is becoming essential.
    Journal of Antimicrobial Chemotherapy 11/2010; 66(2):398-407. · 5.34 Impact Factor
  • Marlieke E.A. de Kraker, Martin Wolkewitz, Hajo Grundmann
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    ABSTRACT: Background: The prevalence of infections caused by resistant E. coli is increasing worldwide. For prioritization in health care determination of the burden of this infection is important. Blood stream infections (BSI) caused by third generation cephalosporin (G3CEP) resistant E. coli (RECO) affect patients that are older, more ill and had a longer hospital stay before infection than patients with G3CEP susceptible E. coli (SECO) BSI, making direct comparisons difficult. In this study modern sampling techniques were used to avoid this problem. Objective: Determine the excess mortality and the excess length of stay attributable to RECO BSI in Europe. Methods: In this study a parallel matched cohort design was used, where patients with an E. coli BSI (exposed) were compared to patients without such a BSI (controls). Two parallel cohorts were constructed, comparing either RECO or SECO exposure. Matching was based on duration of admission prior to enrolment. Thirteen European hospitals, participated in this study from July 2007 to July 2008. Hospital patients were routinely sampled and all patients above 18 years with an E. coli BSI were included as exposed patients. Modern statistical methods were used for comparing mortality and length of stay within the two parallel cohorts: multivariate Cox's regression for competing events and a multivariate generalized linear model with gamma distribution. Results: In total 3509 patients could be included into the study: 111 and 1110 patients had a BSI caused by RECO and SECO, respectively, 2288 patients were included as controls. In-hospital 36% of the RECO BSI patients died compared to 5% of the controls. In the SECO cohort 17% of the exposed patients and 7% of the controls died in the hospital. Cox's regression showed that the hazard for hospital mortality was 5.7 times larger for patients with a RECO BSI than for the controls (confidence interval (CI) 2.5-13.0). These exposed patients had a reduced discharge hazard rate, meaning that they stayed much longer in hospital than the controls. The overall excess length of stay after enrolment for the patients with a RECO BSI was 7.9 days (interquartile range (IQR) 3.5-13.0). In the SECO cohort, the same effects were seen, although the differences were smaller. More exposed patients died (hazard ratio (HR); 2.0, CI 1.5-2.5) and the overall excess length of stay after enrolment for the patients with a SECO BSI was 2.9 days (IQR 1.7-4.0). Overall, G3CEP resistance was associated with excess hospital mortality (HR 2.9, CI 1.2-6.9), as well as an excess length of stay (5.0 days, IQR 0.4-10.2). Conclusions: BSI caused by E. coli increases hospital mortality, as well as the length of stay after enrolment, especially if the pathogen is resistant to G3CEP. Prevention and improved management of infections caused by, especially resistant, gram-negative pathogens within hospitals could reduce a large burden.
    Fifth Decennial International Conference on Health-Care Related Infections 2010; 03/2010
  • Marlieke E.A. de Kraker, Peter Davey, Hajo Grundmann
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    ABSTRACT: Background: To determine the burden of antimicrobial resistance most often patients with an infection caused by a resistant pathogen are compared to patients with the susceptible type of the pathogen (standard' cohort). However, these patient groups often have a very different clinical picture. It is also possible to construct two parallel cohorts, comparing patients with an infection caused by either the susceptible or the resistant pathogen to patients without the infection. In the end the outcomes of the parallel cohort studies can be compared. This design could reduce the residual bias present in the standard design. Objective: In this study we determined the performance of a parallel matched cohort design versus a standard' cohort design to establish the excess mortality related to methicillin resistance in S. aureus blood stream infections (BSI). Methods: In the parallel matched cohort design patients with a S. aureus BSI were compared to patients without such a BSI (controls). Two parallel cohorts were constructed, comparing either methicillin resistant (MRSA) or methicillin susceptible S. aureus (MSSA) exposure. Matching was based on duration of admission prior to enrolment. In the standard cohort design patients with a BSI caused by MRSA were directly compared to patients with a BSI caused by MSSA. In thirteen European hospitals patients were routinely sampled and all patients above 18 years with a S. aureus BSI were included from July 2007 to July 2008. Multivariate logistic regression was used to determine the excess mortality 30 days after infection/enrolment. Results: In the parallel matched cohort design patients with a BSI caused by MRSA had an increased risk of dying compared to controls without a S. aureus BSI (odds ratio (OR) 4.4, confidence interval (CI) 2.8-7.0). For MSSA patients a smaller effect was seen (OR 2.4, CI 1.7-3.3). Combining the two cohorts, the OR for mortality associated with methicillin resistance was 1.8 (CI 1.04-3.2). In the standard cohort the odds for dying for MRSA patients was increased by 1.2 (CI 0.85-1.7) compared to MSSA patients. In the standard design more confounders were identified than in the parallel cohort design. The ROC curves from the three regression models showed that the parallel cohort design gave a better discrimination than the standard cohort design, especially for MRSA parallel cohort. Conclusions: In this case the estimates for 30 day mortality associated with methicillin resistance differed only a little for the two designs. Nevertheless, we believe a parallel matched cohort design is a more valid approach, as the discriminative power of the regression models was higher and less confounders were identified. Next to that, it gives information about the single impact of methicillin resistance, but also about the impact of a MSSA or MRSA BSI compared to patients without this type of infection.
    Fifth Decennial International Conference on Health-Care Related Infections 2010; 03/2010
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    ABSTRACT: Information about the epidemiology of resistance in Streptococcus pneumoniae within southern and eastern countries of the Mediterranean region is incomplete, as reports have been sporadic and difficult to compare. Over a 36-month period, from 2003 to 2005, the ARMed project collected 1298 susceptibility test results of invasive isolates of S. pneumoniae from blood and spinal fluid cultures routinely processed within 59 participating laboratories situated in Algeria, Cyprus, Egypt, Jordan, Lebanon, Malta, Morocco, Tunisia and Turkey. Overall, 26% (335) of isolates were reported as non-susceptible to penicillin, with the highest proportions being reported from Algeria (44%) and Lebanon (40%). During the same time period, the highest proportions of pneumococci that were not susceptible to erythromycin were reported from Malta (46%) and Tunisia (39%). Proportions of dual non-susceptibility in excess of 5% were found in laboratories in Algeria, Tunisia, Lebanon, Jordan and Turkey. ARMed data on the antimicrobial resistance epidemiology of S. pneumoniae in the southern and eastern Mediterranean region provided evidence of high rates of resistance, especially to penicillin. This evidence calls for a greater focus on the identification of relevant drivers of resistance and on the implemention of effective practices in order to address the problem of resistence.
    Clinical Microbiology and Infection 02/2009; 15(3):232-7. · 4.58 Impact Factor
  • Infection 10/2008; 36(5):492-4. · 2.44 Impact Factor
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    ABSTRACT: From January 2003 to December 2005, 5091 susceptibility test results from invasive isolates of Escherichia coli, collected from blood cultures and cerebrospinal fluid routinely processed within 58 participating laboratories, were investigated. These laboratories in turn serviced 64 hospitals in Algeria, Cyprus, Egypt, Jordan, Lebanon, Malta, Morocco, Tunisia and Turkey. The median proportion of resistance to third-generation cephalosporins for the duration of the project was 18.9% (interquartile range (IQR): 12.5-30.8%), and for fluoroquinolones 21.0% (IQR: 7.7-32.6%). A substantial proportion of strains reported by laboratories in countries east of the Mediterranean exhibited evidence of multiresistance, the highest proportion being from Egypt (31%). There is clearly a need for further investigation of potential causes of the significant resistance identified, as well as for strengthening of national and international surveillance initiatives within this region.;
    Clinical Microbiology and Infection 09/2008; 14(8):789-96. · 4.58 Impact Factor
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    ABSTRACT: Efforts aimed at curtailing the ever increasing spread of methicillin-resistant Staphylococcus aureus (MRSA) require effective information of its epidemiology. However, knowledge about the situation in southern and eastern countries of the Mediterranean is incomplete since reports have been sporadic and difficult to compare. Over a 36 month period from 2003 to 2005, the ARMed project collected more than 5000 susceptibility test results of invasive isolates of S. aureus from blood cultures routinely processed within participating laboratories servicing 62 hospitals situated in Algeria, Cyprus, Egypt, Jordan, Lebanon, Malta, Morocco, Tunisia and Turkey. Overall, the median MRSA proportion was 39% (interquartile range: 27.1% to 51.1%). The highest proportions of MRSA were reported by Jordan, Egypt and Cyprus, where more than 50% of the invasive isolates were methicillin-resistant. Considerable variation was identified in the proportion of MRSA in hospitals within the same country. It appears that most of the countries in the Mediterranean region are experiencing a surge in MRSA infections. This requires a greater focus to identify relevant drivers of resistance and implement effective practices in order to address them, especially improved infection control and antibiotic consumption practices.
    Journal of Antimicrobial Chemotherapy 01/2008; 60(6):1310-5. · 5.34 Impact Factor
  • Euro surveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 04/2007; 12(3):E070315.3. · 5.49 Impact Factor
  • International Journal of Antimicrobial Agents 03/2007; 29. · 4.42 Impact Factor
  • International Journal of Antimicrobial Agents 03/2007; 29. · 4.42 Impact Factor
  • International Journal of Antimicrobial Agents - INT J ANTIMICROBIAL AGENTS. 01/2007; 29.
  • International Journal of Antimicrobial Agents - INT J ANTIMICROBIAL AGENTS. 01/2007; 29.
  • International Journal of Antimicrobial Agents - INT J ANTIMICROBIAL AGENTS. 01/2007; 29.
  • International Journal of Antimicrobial Agents - INT J ANTIMICROBIAL AGENTS. 01/2007; 29.

Publication Stats

257 Citations
94.56 Total Impact Points

Institutions

  • 2011
    • Universitair Medisch Centrum Groningen
      Groningen, Groningen, Netherlands
  • 2006–2011
    • National Institute for Public Health and the Environment (RIVM)
      • • Centre for Infectious Disease Control (CIb)
      • • Epidemiology and Surveillance Unit (EPI)
      Utrecht, Provincie Utrecht, Netherlands
  • 2009
    • Mater Dei Hospital
      La Valette, Il-Belt Valletta, Malta