Hajo Grundmann

Universitair Medisch Centrum Groningen, Groningen, Groningen, Netherlands

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Publications (133)711.15 Total impact

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    ABSTRACT: As MRSA are considered Staphylococcus aureus isolates with oxacillin minimum inhibitory concentration (MIC) of ≥4 mg/L or harboring the mecA gene. However, the presence of mecA does not necessarily lead to oxacillin resistance and mecA gene-carrying isolates may have oxacillin MIC within the susceptible range (≤2 mg/L). During the last few years it has become apparent that oxacillin-susceptible (OS) mecA-positive S. aureus isolates (commonly called OS-MRSA) are rather commonly detected worldwide and may remain undiagnosed using phenotypic susceptibility testing methods. This review will summarize the current reports on OS-MRSA isolations and the underlying mechanisms regulating the expression of oxacillin resistance and also oxacillin susceptibility in mecA-positive S. aureus isolates. As MRSA commonly cause severe infections against which effective therapies are limited, understanding of these mechanisms could enable the identification of new targets for the treatment or reversion of the MRSA phenotype.
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    ABSTRACT: There is still limited knowledge about the prevalence and risk factors of nasal carriage for Staphylococcus aureus among healthy carriers in China. We investigated 2448 healthy adults (≥18 years of age) from Beijing (n = 1530) and Harbin (n = 918) by nasal screening. Participants were checked for carriage of S. aureus, and health-related and demographic information between 2009 and 2011 was gathered. A total of 403 S. aureus (403/2448, 16.5%) were recovered, 8 of which were methicillin resistant (8/2448, 0.33%). Three factors were independently associated with S. aureus nasal carriage: Harbin as city of residence (odds ratio (OR) = 2.0, 95% confidence interval (CI) = 1.41 to 2.85), age ≤24 years (OR = 1.77, 95% CI = 1.30-2.44) and non-Han ethnicity (OR = 1.58, 95% CI = 1.05 to 2.38). On the basis of population genetic analysis using multiple locus variable number of tandem repeats analysis (MLVA) and spa typing, MLVA complex (MC) 398 and MC5a were the most prevalent clonal lineages in this collection. In multivariate models, residing in Harbin (OR = 1.77, 95% CI = 1.07-2.92) and having household members in the healthcare profession (OR = 3.69, 95% CI = 1.14-11.92) were factors associated with carriage of clonal lineage MC398. On the other hand, female sex (OR = 3.15, 95% CI = 1.35-7.33) and a history of chronic liver disease (OR = 16.93, 95% CI = 2.91-98.59) were associated with the clonal lineage MC5a. The three most common spa types were t571 (10.9%), t189 (9.9%) and t701 (7.2%). These findings provide insight into the determinants of nasal carriage and ecology for some of the most successful strains of S. aureus among healthy people in Northern China. Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
    Clinical Microbiology and Infection 02/2015; 21:157-162. DOI:10.1016/j.cmi.2014.08.023 · 5.20 Impact Factor
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    ABSTRACT: The presence of the arginine catabolic mobile element (ACME) in Staphylococcus aureus has been reported to enhance the colonization of the human host. The aim of this study was to determine the genetic organization of composite islands harbouring ACME. Two ACME-positive S. aureus isolates obtained during two different surveys conducted in the Netherlands and Poland were characterized in this study. The isolates were analysed by spa typing, DNA microarrays and whole-genome sequencing. The two isolates harboured a truncated yet fully functional ACME type II with an identical nucleotide sequence, but differed in their adjacent mobile genetic elements. The first strain was a livestock-associated ST398-t011 MRSA, which had a staphylococcal cassette chromosome mec (SCCmec) composite island composed of SCCpls adjacent to orfX followed by ACME type II and SCCmec type IVa. The second ACME-positive isolate was an ST8-t008 MSSA. Its composite island showed an SCC-like element carrying the ccrC gene followed by ACME II. This is the first report of an ACME in a livestock-associated MRSA ST398. It is also the first presentation of an ACME composite island structure in an MSSA isolate. Our findings indicate an extensive mosaicism of composite islands in S. aureus, which has implications for the transmissibility among humans and thus for public health. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.
    Journal of Antimicrobial Chemotherapy 01/2015; 70(5). DOI:10.1093/jac/dku531 · 5.44 Impact Factor
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    ABSTRACT: Major challenges remain when attempting to quantify and evaluate the impacts of contaminated environments and heterogeneity in the cohorting of health care workers (HCWs) on hospital infections. Data on the detection rate of multidrug-resistant Acinetobacter baumannii (MRAB) in a Chinese intensive care unit (ICU) were obtained to accurately evaluate the level of environmental contamination and also to simplify existing models. Data-driven mathematical models, including mean-field and pair approximation models, were proposed to examine the comprehensive effect of integrated measures including cohorting, increasing nurse-patient ratios and improvement of environmental sanitation on MRAB infection. Our results indicate that for clean environments and with strict cohorting, increasing the nurse-patient ratio results in an initial increase and then a decline in MRAB colonization. In contrast, in contaminated environments, increasing the nurse-patient ratio may lead to either a consistent increase or an initial increase followed by a decline of MRAB colonization, depending on the level of environmental contamination and the cohorting rate. For developing more effective control strategies, the findings suggest that increasing the cohorting rate and nurse-patient ratio are effective interventions for relatively clean environments, while cleaning the environment more frequently and increasing hand washing rate are suitable measures in contaminated environments.
    Scientific Reports 01/2015; 5:9478. DOI:10.1038/srep09478 · 5.08 Impact Factor
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    ABSTRACT: Shiga toxin-producing Escherichia coli (STEC) O104:H4 emerged as an important pathogen when it caused a large outbreak in Germany in 2011. Little is known about the evolutionary history and genomic diversity of the bacterium. The current communication describes a comprehensive analysis of STEC O104:H4 genomes from the 2011 outbreak and other non-outbreak-related isolates. Outbreak-related isolates formed a tight cluster that shared a monophyletic relation with two non-outbreak clusters, suggesting that all three clusters originated from a common ancestor. Eight single nucleotide polymorphisms, seven of which were non-synonymous, distinguished outbreak from non-outbreak isolates. Lineage-specific markers indicated that recent partitions were driven by selective pressures associated with niche adaptation. Based on the results, an evolutionary model for STEC O104:H4 is proposed. Our analysis provides the evolutionary context at population level and describes the emergence of clones with novel properties, which is necessary for developing comprehensive approaches to early warning and control. Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
    Clinical Microbiology and Infection 12/2014; DOI:10.1016/j.cmi.2014.12.009 · 5.20 Impact Factor
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    ABSTRACT: Staphylococcus aureus is one of the most important human pathogens and meticillin-resistant S. aureus (MRSA) presents a major cause of healthcare- and community-acquired infections. This study investigated the spatial and temporal changes of S. aureus causing bacteraemia in Europe over a five-year interval and explored the possibility of integrating pathogen-based typing data with epidemiological and clinical information at a European level. Between January 2011 and July 2011, 350 laboratories serving 453 hospitals in 25 countries collected 3,753 isolates (meticillin-sensitive S. aureus (MSSA) and MRSA) from patients with S. aureus bloodstream infections. All isolates were sent to the national staphylococcal reference laboratories and characterised by quality-controlled spa typing. Data were uploaded to an interactive web-based mapping tool. A wide geographical distribution of spa types was found, with some prevalent in all European countries. MSSA was more diverse than MRSA. MRSA differed considerably between countries with major international clones expanding or receding when compared to a 2006 survey. We provide evidence that a network approach of decentralised typing and visualisation of aggregated data using an interactive mapping tool can provide important information on the dynamics of S. aureus populations such as early signalling of emerging strains, cross-border spread and importation by travel.
    Eurosurveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 12/2014; 19(49):20987. · 4.66 Impact Factor
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    ABSTRACT: The objective of this review was to provide an up-to-date account of the interventions used to prevent the introduction of meticillin-resistant Staphylococcus aureus (MRSA) from the expanding community and livestock reservoirs into hospitals in the USA, Denmark, The Netherlands and Western Australia. A review of existing literature and local guidelines for the management of MRSA in hospitals was performed. In Denmark, The Netherlands and Western Australia, where the prevalence of MRSA is relatively low, targeted admission screening and isolation of predefined high-risk populations have been used for several decades to successfully control MRSA in the hospital. Furthermore, in Denmark and The Netherlands, all identified MRSA carriers undergo routine decolonisation, whereas only carriers of particularly transmissible or virulent MRSA clones are subjected to decolonisation in Western Australia. In the USA, which continues to be a high-prevalence MRSA country, policies vary by state and even by hospital, and whilst guidelines from professional organisations provide a framework for infection control practices, these guidelines lack the authority of a legislative mandate. In conclusion, the changing epidemiology of MRSA, exemplified by the recent emergence of MRSA in the community and in food animals, makes it increasingly difficult to accurately identify specific high-risk groups to screen for MRSA carriage. Understanding the changing epidemiology of MRSA in a local as well as global context is fundamental to prevent the introduction of MRSA into hospitals.
    12/2014; 2(4). DOI:10.1016/j.jgar.2014.09.003
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    ABSTRACT: Methicillin-resistant Staphylococcus aureus (MRSA) belonging to the multilocus sequence type clonal complex 59 (MLST CC59) is the predominant community-associated MRSA clone in Asia. This clone, which is primarily linked with the spa type t437, has so far only been reported in low numbers among large epidemiological studies in Europe. Nevertheless, the overall numbers identified in some Northern European reference laboratories have increased during the past decade. To determine whether the S. aureus t437 clone is present in other European countries, and to assess its genetic diversity across Europe, we analysed 147 S. aureus t437 isolates from 11 European countries collected over a period of 11 years using multiple locus variable number tandem repeat fingerprinting/analysis (MLVF/MLVA) and MLST. Additionally 16 S. aureus t437 isolates from healthy carriers and patients from China were included. Most isolates were shown to be monophyletic with 98% of the isolates belonging to the single MLVA complex 621, to which nearly all included isolates from China also belonged. More importantly, all MLST-typed isolates belonged to CC59. Our study implies that the European S. aureus t437 population represents a genetically tight cluster, irrespective of the year, country and site of isolation. This underpins the view that S. aureus CC59 has been introduced into several European countries, not being restricted to particular geographical regions or specific host environments. The European S. aureus t437 isolates thus bear the general hallmarks of a high-risk clone. Copyright © 2014 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.
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    ABSTRACT: The population-level appropriateness of empirical antibiotic therapy can be conventionally measured by ascertainment of treatment coverage. This method involves a complex resource-intensive case-by-case assessment of the prescribed antibiotic treatment and the resistance of the causative microorganism. We aimed to develop an alternative approach based, instead, on the use of routinely available surveillance data.
    Journal of Antimicrobial Chemotherapy 08/2014; DOI:10.1093/jac/dku336 · 5.44 Impact Factor
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    ABSTRACT: BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) is an important nosocomial pathogen but little is known about its circulation in hospitals in developing countries. We aimed to describe carriage of S.aureus amongst inpatients in a mid-sized Kenyan government hospital.MethodsWe determined the frequency of S.aureus and MRSA carriage amongst inpatients in Thika Hospital, Kenya by means of repeated cross-sectional ward surveys. For all S.aureus isolates, we performed antibiotic susceptibility tests, genomic profiling using a DNA microarray and spa typing and MLST.ResultsIn this typical mid-sized Kenyan Government hospital, we performed 950 screens for current carriage of S.aureus amongst inpatients over a four month period. We detected S.aureus carriage (either MSSA or MRSA) in 8.9% (85/950; 95%CI 7.1-10.8) of inpatient screens, but patients with multiple screens were more likely have detection of carriage. MRSA carriage was rare amongst S.aureus strains carried by hospital inpatients – only 7.0% (6/86; 95%CI 1.5-12.5%) of all isolates were MRSA. Most MRSA (5/6) were obtained from burns patients with prolonged admissions, who only represented a small proportion of the inpatient population. All MRSA strains were of the same clone (MLST ST239; spa type t037) with concurrent resistance to multiple antibiotic classes. MSSA isolates were diverse and rarely expressed antibiotic resistance except against benzyl-penicillin and co-trimoxazole.ConclusionsAlthough carriage rates for S.aureus and the MRSA prevalence in this Kenyan hospital were both low, burns patient were identified as a high risk group for carriage. The high frequency of genetically indistinguishable isolates suggests that there was local transmission of both MRSA and MSSA.
    07/2014; 3:22. DOI:10.1186/2047-2994-3-22
  • The Lancet Infectious Diseases 07/2014; 14(7):550–551. DOI:10.1016/S1473-3099(14)70709-1 · 19.45 Impact Factor
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    ABSTRACT: The Staphylococcal Cassette Chromosome mec (SCCmec) confers methicillin resistance to Staphylococcus aureus. While SCCmec is generally regarded as a mobile genetic element, the precise mechanisms by which large SCCmec elements are exchanged between staphylococci have remained enigmatic. In the present studies, we observed that the clinical methicillin-resistant S. aureus (MRSA) isolate UMCG-M4 with the sequence type 398 contains four prophages belonging to the serological groups A, B and Fa. Previous studies have shown that certain serological group B bacteriophages of S. aureus are capable of generalized transduction. We therefore assessed the transducing capabilities of the phages from strain UMCG-M4. The results show that some of these phages can indeed transduce plasmid pT181 to the recipient S. aureus strain RN4220. Therefore, we also investigated the possible involvement of these transducing phages in the transmission of the large SCCmec type V (5C2&5) element of S. aureus UMCG-M4. While no transduction of the complete SCCmec element was observed, we were able to demonstrate that purified phage particles did contain large parts of the SCCmec element of the donor strain, including the methicillin resistance gene mecA. This shows that staphylococcal phages can encapsulate the resistance determinant mecA of a large SCCmec type V (5C2&5) element, which may lead to its transfer to other staphylococci.
    International journal of medical microbiology: IJMM 06/2014; 304(5-6). DOI:10.1016/j.ijmm.2014.05.010 · 3.42 Impact Factor
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    Hajo Grundmann
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    ABSTRACT: Abstract The need for global data about the scale of antibiotic resistance (ABR) in a geographical explicit and timely manner has been identified by many stakeholders, including the World Health Organization. This primer should help defining the objectives, scale, scope, and structure of possible future efforts. Stakeholders and their expected information demands were identified to generate an inventory of surveillance objectives. For simplification, an original approach was chosen to bundle sets of objectives that represent common demands and can be addressed by common subject areas, which fall into three areas. Subject area I addresses clinical demands and focuses on patients; subject area II addresses public health demands by focusing on meta-populations; subject area III addresses infection control demands and focuses on pathogens. A division into these areas leads to a separation of surveillance activities suggesting a modular approach which can provide complementary information. Moreover, the modules address the conundrum of ABR at the complementary levels of 1) patient, 2) population, and 3) pathogen, which-rather conventionally-follow the operational and professional fault-lines of the main disciplines involved, namely clinical medicine, public health, and biology. Essential features that define different surveillance systems have been listed and taken into consideration when suggesting templates for future efforts. Putting ABR on the global health map is a daunting task as it requires acceptance, agreements, and engagement but also concessions at many different levels. Given the existing gaps in the global diagnostic service landscape only a step-wise approach which defines achievable aims, objectives, and milestones will succeed to produce a sustainable system of international co-operative surveillance of ABR.
    Upsala journal of medical sciences 04/2014; 119(2). DOI:10.3109/03009734.2014.904458 · 1.71 Impact Factor
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    ABSTRACT: In 2008, an intensive care unit (ICU) in a large Chinese hospital was moved from a 6-bed old ward to a 20-bed new ward. After the move, the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in patients and environmental sites decreased significantly, but the number of ICU-acquired cases per imported MRSA case increased from 1.4 to 4.1. This study suggests that the nurse cohorting level and hand hygiene compliance are strong predicators of MRSA transmission in ICUs.
    American journal of infection control 04/2014; 42(4):436–438. DOI:10.1016/j.ajic.2013.11.019 · 2.33 Impact Factor
  • Eurosurveillance: bulletin europeen sur les maladies transmissibles = European communicable disease bulletin 03/2014; 19(9). DOI:10.2807/1560-7917.ES2014.19.9.20723 · 4.66 Impact Factor
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    ABSTRACT: Early detection of new or novel variants of nosocomial pathogens is a public health priority. We show that, for healthcare-associated infections that spread between hospitals as a result of patient movements, it is possible to design an effective surveillance system based on a relatively small number of sentinel hospitals. We apply recently developed mathematical models to patient admission data from the national healthcare systems of England and The Netherlands. Relatively short detection times are achieved once 10-20% hospitals are recruited as sentinels and only modest reductions are seen as more hospitals are recruited thereafter. Using a heuristic optimization approach to sentinel selection, the same expected time to detection can be achieved by recruiting approximately half as many hospitals. Our study provides a robust evidence base to underpin the design of an efficient sentinel hospital surveillance system for novel nosocomial pathogens, delivering early detection times for reduced expenditure and effort.
    Proceedings of the National Academy of Sciences 01/2014; 111(6). DOI:10.1073/pnas.1308062111 · 9.81 Impact Factor
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    ABSTRACT: The Staphylococcal Cassette Chromosome mec (SCCmec) confers methicillin resistance to Staphylococcus aureus. While SCCmec is generally regarded as a mobile genetic element, the precise mechanisms by which large SCCmec elements are exchanged between staphylococci have remained enigmatic. In the present studies, we observed that the clinical methicillin-resistant S. aureus (MRSA) isolate UMCG-M4 with the sequence type 398 contains four prophages belonging to the serological groups A, B and Fa. Previous studies have shown that certain serological group B bacteriophages of S. aureus are capable of generalized transduction. We therefore assessed the transducing capabilities of the phages from strain UMCG-M4. The results show that some of these phages can indeed transduce plasmid pT181 to the recipient S. aureus strain RN4220. Therefore, we also investigated the possible involvement of these transducing phages in the transmission of the large SCCmec type V (5C2&5) element of S. aureus UMCG-M4. While no transduction of the complete SCCmec element was observed, we were able to demonstrate that purified phage particles did contain large parts of the SCCmec element of the donor strain, including the methicillin resistance gene mecA. This shows that staphylococcal phages can encapsulate the resistance determinant mecA of a large SCCmec type V (5C2&5) element, which may lead to its transfer to other staphylococci.
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Publication Stats

6k Citations
711.15 Total Impact Points

Institutions

  • 2008–2015
    • Universitair Medisch Centrum Groningen
      • Department of Medical Microbiology
      Groningen, Groningen, Netherlands
    • Universitätsklinikum Münster
      • Institut für Hygiene
      Münster, North Rhine-Westphalia, Germany
  • 2006–2015
    • University of Groningen
      • Department of Medical Microbiology
      Groningen, Groningen, Netherlands
  • 2013
    • Creighton University
      • Department of Medical Microbiology and Immunology
      Omaha, NE, United States
  • 2012
    • Universitetet i Tromsø
      Tromsø, Troms, Norway
  • 2005–2012
    • National Institute for Public Health and the Environment (RIVM)
      • • Centre for Infectious Disease Control (CIb)
      • • Epidemiology and Surveillance Unit (EPI)
      Utrecht, Provincie Utrecht, Netherlands
    • Robert Koch Institut
      Berlín, Berlin, Germany
  • 1996–2004
    • University of Nottingham
      • • Centre for Sports Medicine
      • • Faculty of Medicine and Health Sciences
      Nottigham, England, United Kingdom
  • 2003
    • Utrecht University
      Utrecht, Utrecht, Netherlands
  • 1993–2002
    • University of Freiburg
      • Institute of Medical Biometry and Medical Informatics
      Freiburg, Baden-Württemberg, Germany