Hajo Grundman | University of Groningen (original) (raw)

Papers by Hajo Grundman

Research paper thumbnail of Typing of Austrian Listeria monocytogenes isolates by automated laser fluorescence analysis of randomly amplified polymorphic DNA

Zentralblatt für Bakteriologie : international journal of medical microbiology, 1997

We used automated laser fluorescence analysis of randomly amplified polymorphic DNA (RAPD-Alfa) t... more We used automated laser fluorescence analysis of randomly amplified polymorphic DNA (RAPD-Alfa) to study the epidemiology of listeriosis in western Austria. There were no discrepancies between RAPD-Alfa patterns and serotypes found in 18 food isolates and 18 clinical isolates. The results of our study suggest that the food isolates typed were not at the origin of the human cases in western Austria. Using RAPD-Alfa, it was possible to link 9 out of 16 "sporadic" Listeria infections (mother-child cases counted as one) to the occurrence of other cases. Our results underline the necessity of epidemiological clarification of listeriosis cases as a prerequisite for specific preventive measures by public health services (e.g. confiscation of contaminated food products, issue of public warnings). To establish the chain of infection, more is needed than just speciation of bacteria in incriminated food products. Automated laser fluorescence analysis of randomly amplified polymorphic...

Research paper thumbnail of Methicillin-resistant Staphylococcus aureus in Europe, 1999-2002

Emerging infectious diseases, 2004

We explored the variation in proportions of methicillin-resistant Staphylococcus aureus (MRSA) be... more We explored the variation in proportions of methicillin-resistant Staphylococcus aureus (MRSA) between and within countries participating in the European Antimicrobial Resistance Surveillance System and temporal trends in its occurrence. This system collects routine antimicrobial susceptibility tests for S. aureus. We examined data collected from January 1999 through December 2002 (50,759 isolates from 495 hospitals in 26 countries). MRSA prevalence varied almost 100-fold, from <1% in northern Europe to >40% in southern and western Europe. MRSA proportions significantly increased in Belgium, Germany, Ireland, the Netherlands, and the United Kingdom, and decreased in Slovenia. Within countries, MRSA proportions varied between hospitals with highest variance in countries with a prevalence of 5% to 20%. The observed trends should stimulate initiatives to control MRSA at national, regional, and hospital levels. The large differences between hospitals indicate that efforts may be m...

Research paper thumbnail of Determining the Genetic Structure of the Natural Population of Staphylococcus aureus: a Comparison of Multilocus Sequence Typing with Pulsed-Field Gel Electrophoresis, Randomly Amplified Polymorphic DNA Analysis, and Phage Typing

Journal of Clinical Microbiology, 2002

We used a sample of Staphylococcus aureus strains that are carried by humans and that are represe... more We used a sample of Staphylococcus aureus strains that are carried by humans and that are representative of the natural population of S. aureus strains in order to assess the value of multilocus sequence typing (MLST), pulsed-field gel electrophoresis, randomly amplified polymorphic DNA analysis, and phage typing as epidemiological tools. Only MLST was able to define clonal complexes unambiguously. All DNA-based typing approaches achieved a high degree of agreement, implying phylogenetic concordance, but predicted epidemiological associations with variable accuracy.

Research paper thumbnail of Genodiversity of Resistant Pseudomonas aeruginosa Isolates in Relation to Antimicrobial Usage Density and Resistance Rates in Intensive Care Units

Infection Control and Hospital Epidemiology, 2008

To evaluate the assumption that resistance rates in intensive care units (ICUs) are markedly infl... more To evaluate the assumption that resistance rates in intensive care units (ICUs) are markedly influenced by cross-transmission events in addition to high rates of antimicrobial usage. This was a prospective ICU- and laboratory-based surveillance study involving 35 German ICUs from 1999 through 2004. A total of 585 ciprofloxacin- or imipenem-resistant isolates of Pseudomonas aeruginosa were investigated together with resistance rate and unit-based antimicrobial usage density. Antimicrobial use was reported in terms of defined daily doses per 1,000 patient-days. All the strains were assigned to ICU-based genotypes. Genodiversity was calculated as the numbers of indistinguishable ICU-based genotypes found per isolates tested. Reduced ICU-based genodiversity was taken as an indirect measure of frequently occurring cross-transmission events. The genodiversity of ciprofloxacin- and imipenem-resistant P. aeruginosa isolates was significantly lower (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;=, by Fisher exact test) in ICUs with high resistance rate and low antimicrobial usage density (genodiversity, 0.50 and 0.50, respectively) than in ICUs that featured low resistance rate in the presence of high antimicrobial usage density (genodiversity, 0.90 and 0.95, respectively). In ICUs with low genodiversity, there was a greater rise in resistance rate with increasing antimicrobial usage density, compared with that in ICUs with high diversity. This study on resistant P. aeruginosa isolates supports the assumption that high resistance rate in the presence of low antimicrobial usage density results from more-frequent cross-transmission events. A greater rise in resistance rate with increasing antimicrobial usage density in ICUs with low genodiversity indicates that resistance rate in ICUs might be markedly determined by cross-transmission events other than antimicrobial usage.

Research paper thumbnail of Global Spread of Vancomycin resistant Enterococcus faecium from Distinct Nosocomial Genetic Complex

Vancomycin-resistant enterococci (VRE) have caused hospital outbreaks worldwide, and the vancomyc... more Vancomycin-resistant enterococci (VRE) have caused hospital outbreaks worldwide, and the vancomycin-resistance gene (vanA) has crossed genus boundaries to methicillin-resistant Staphylococcus aureus. Spread of VRE, therefore, represents an immediate threat for patient care and creates a reservoir of mobile resistance genes for other, more virulent pathogens. Evolutionary genetics, population structure, and geographic distribution of 411 VRE and vancomycin-susceptible Enterococcus faecium isolates, recovered from human and nonhuman sources and community and hospital reservoirs in 5 continents, identified a genetic lineage of E. faecium (complex-17) that has spread globally. This lineage is characterized by 1) ampicillin resistance, 2) a pathogenicity island, and 3) an association with hospital outbreaks. Complex-17 is an example of cumulative evolutionary processes that improved the relative fitness of bacteria in hospital environments. Preventing further spread of this epidemic E. faecium subpopulation is critical, and efforts should focus on the early disclosure of ampicillin-resistant complex-17 strains.

Research paper thumbnail of The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA)

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital-acquired infectio... more Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital-acquired infections that are becoming increasingly difficult to combat because of emerging resistance to all current antibiotic classes. The evolutionary origins of MRSA are poorly understood, no rational nomenclature exists, and there is no consensus on the number of major MRSA clones or the relatedness of clones described from different countries. We resolve all of these issues and provide a more thorough and precise analysis of the evolution of MRSA clones than has previously been possible. Using multilocus sequence typing and an algorithm, BURST, we analyzed an international collection of 912 MRSA and methicillinsusceptible S. aureus (MSSA) isolates. We identified 11 major MRSA clones within five groups of related genotypes. The putative ancestral genotype of each group and the most parsimonious patterns of descent of isolates from each ancestor were inferred by using BURST, which, together with analysis of the methicillin resistance genes, established the likely evolutionary origins of each major MRSA clone, the genotype of the original MRSA clone and its MSSA progenitor, and the extent of acquisition and horizontal movement of the methicillin resistance genes. Major MRSA clones have arisen repeatedly from successful epidemic MSSA strains, and isolates with decreased susceptibility to vancomycin, the antibiotic of last resort, are arising from some of these major MRSA clones, highlighting a depressing progression of increasing drug resistance within a small number of ecologically successful S. aureus genotypes.

Research paper thumbnail of A framework for global surveillance of antibiotic resistance

Drug Resistance Updates, 2011

The foreseen decline in antibiotic effectiveness explains the needs for data to inform the global... more The foreseen decline in antibiotic effectiveness explains the needs for data to inform the global public health agenda about the magnitude and evolution of antibiotic resistance as a serious threat to human health and development. Opportunistic bacterial pathogens are the cause of the majority of community and hospital-acquired infections worldwide. We provide an inventory of pre-existing regional surveillance programs in the six WHO regions which should form the underpinning for the consolidation of a global network infrastructure and we outline the structural components such as an international network of reference laboratories that need to be put in place to address the void of these crucial data. In addition we suggest to make use of existing Health and Demographic Surveillance Sites (HDSS) to obtain crucial information from communities in resource limited settings at household level in low-and middleincome countries in Asia and Africa. For optimising the use of surveillance data for public health action i.e. priority setting for new drug development, comparative quantification of antibiotic effectiveness at local, national, regional and global level and identification of the action gaps can be helpful.

Research paper thumbnail of Multicenter evaluation of epidemiological typing of methicillin-resistant Staphylococcus aureus strains by repetitive-element PCR analysis

Journal of clinical …, 2000

Rapid and efficient epidemiologic typing systems would be useful to monitor transmission of methi... more Rapid and efficient epidemiologic typing systems would be useful to monitor transmission of methicillin-resistant Staphylococcus aureus (MRSA) at both local and interregional levels. To evaluate the intralaboratory performance and interlaboratory reproducibility of three ...

Research paper thumbnail of Typing of Austrian Listeria monocytogenes isolates by automated laser fluorescence analysis of randomly amplified polymorphic DNA

Zentralblatt für Bakteriologie : international journal of medical microbiology, 1997

We used automated laser fluorescence analysis of randomly amplified polymorphic DNA (RAPD-Alfa) t... more We used automated laser fluorescence analysis of randomly amplified polymorphic DNA (RAPD-Alfa) to study the epidemiology of listeriosis in western Austria. There were no discrepancies between RAPD-Alfa patterns and serotypes found in 18 food isolates and 18 clinical isolates. The results of our study suggest that the food isolates typed were not at the origin of the human cases in western Austria. Using RAPD-Alfa, it was possible to link 9 out of 16 "sporadic" Listeria infections (mother-child cases counted as one) to the occurrence of other cases. Our results underline the necessity of epidemiological clarification of listeriosis cases as a prerequisite for specific preventive measures by public health services (e.g. confiscation of contaminated food products, issue of public warnings). To establish the chain of infection, more is needed than just speciation of bacteria in incriminated food products. Automated laser fluorescence analysis of randomly amplified polymorphic...

Research paper thumbnail of Methicillin-resistant Staphylococcus aureus in Europe, 1999-2002

Emerging infectious diseases, 2004

We explored the variation in proportions of methicillin-resistant Staphylococcus aureus (MRSA) be... more We explored the variation in proportions of methicillin-resistant Staphylococcus aureus (MRSA) between and within countries participating in the European Antimicrobial Resistance Surveillance System and temporal trends in its occurrence. This system collects routine antimicrobial susceptibility tests for S. aureus. We examined data collected from January 1999 through December 2002 (50,759 isolates from 495 hospitals in 26 countries). MRSA prevalence varied almost 100-fold, from <1% in northern Europe to >40% in southern and western Europe. MRSA proportions significantly increased in Belgium, Germany, Ireland, the Netherlands, and the United Kingdom, and decreased in Slovenia. Within countries, MRSA proportions varied between hospitals with highest variance in countries with a prevalence of 5% to 20%. The observed trends should stimulate initiatives to control MRSA at national, regional, and hospital levels. The large differences between hospitals indicate that efforts may be m...

Research paper thumbnail of Determining the Genetic Structure of the Natural Population of Staphylococcus aureus: a Comparison of Multilocus Sequence Typing with Pulsed-Field Gel Electrophoresis, Randomly Amplified Polymorphic DNA Analysis, and Phage Typing

Journal of Clinical Microbiology, 2002

We used a sample of Staphylococcus aureus strains that are carried by humans and that are represe... more We used a sample of Staphylococcus aureus strains that are carried by humans and that are representative of the natural population of S. aureus strains in order to assess the value of multilocus sequence typing (MLST), pulsed-field gel electrophoresis, randomly amplified polymorphic DNA analysis, and phage typing as epidemiological tools. Only MLST was able to define clonal complexes unambiguously. All DNA-based typing approaches achieved a high degree of agreement, implying phylogenetic concordance, but predicted epidemiological associations with variable accuracy.

Research paper thumbnail of Genodiversity of Resistant Pseudomonas aeruginosa Isolates in Relation to Antimicrobial Usage Density and Resistance Rates in Intensive Care Units

Infection Control and Hospital Epidemiology, 2008

To evaluate the assumption that resistance rates in intensive care units (ICUs) are markedly infl... more To evaluate the assumption that resistance rates in intensive care units (ICUs) are markedly influenced by cross-transmission events in addition to high rates of antimicrobial usage. This was a prospective ICU- and laboratory-based surveillance study involving 35 German ICUs from 1999 through 2004. A total of 585 ciprofloxacin- or imipenem-resistant isolates of Pseudomonas aeruginosa were investigated together with resistance rate and unit-based antimicrobial usage density. Antimicrobial use was reported in terms of defined daily doses per 1,000 patient-days. All the strains were assigned to ICU-based genotypes. Genodiversity was calculated as the numbers of indistinguishable ICU-based genotypes found per isolates tested. Reduced ICU-based genodiversity was taken as an indirect measure of frequently occurring cross-transmission events. The genodiversity of ciprofloxacin- and imipenem-resistant P. aeruginosa isolates was significantly lower (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;=, by Fisher exact test) in ICUs with high resistance rate and low antimicrobial usage density (genodiversity, 0.50 and 0.50, respectively) than in ICUs that featured low resistance rate in the presence of high antimicrobial usage density (genodiversity, 0.90 and 0.95, respectively). In ICUs with low genodiversity, there was a greater rise in resistance rate with increasing antimicrobial usage density, compared with that in ICUs with high diversity. This study on resistant P. aeruginosa isolates supports the assumption that high resistance rate in the presence of low antimicrobial usage density results from more-frequent cross-transmission events. A greater rise in resistance rate with increasing antimicrobial usage density in ICUs with low genodiversity indicates that resistance rate in ICUs might be markedly determined by cross-transmission events other than antimicrobial usage.

Research paper thumbnail of Global Spread of Vancomycin resistant Enterococcus faecium from Distinct Nosocomial Genetic Complex

Vancomycin-resistant enterococci (VRE) have caused hospital outbreaks worldwide, and the vancomyc... more Vancomycin-resistant enterococci (VRE) have caused hospital outbreaks worldwide, and the vancomycin-resistance gene (vanA) has crossed genus boundaries to methicillin-resistant Staphylococcus aureus. Spread of VRE, therefore, represents an immediate threat for patient care and creates a reservoir of mobile resistance genes for other, more virulent pathogens. Evolutionary genetics, population structure, and geographic distribution of 411 VRE and vancomycin-susceptible Enterococcus faecium isolates, recovered from human and nonhuman sources and community and hospital reservoirs in 5 continents, identified a genetic lineage of E. faecium (complex-17) that has spread globally. This lineage is characterized by 1) ampicillin resistance, 2) a pathogenicity island, and 3) an association with hospital outbreaks. Complex-17 is an example of cumulative evolutionary processes that improved the relative fitness of bacteria in hospital environments. Preventing further spread of this epidemic E. faecium subpopulation is critical, and efforts should focus on the early disclosure of ampicillin-resistant complex-17 strains.

Research paper thumbnail of The evolutionary history of methicillin-resistant Staphylococcus aureus (MRSA)

Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital-acquired infectio... more Methicillin-resistant Staphylococcus aureus (MRSA) is a major cause of hospital-acquired infections that are becoming increasingly difficult to combat because of emerging resistance to all current antibiotic classes. The evolutionary origins of MRSA are poorly understood, no rational nomenclature exists, and there is no consensus on the number of major MRSA clones or the relatedness of clones described from different countries. We resolve all of these issues and provide a more thorough and precise analysis of the evolution of MRSA clones than has previously been possible. Using multilocus sequence typing and an algorithm, BURST, we analyzed an international collection of 912 MRSA and methicillinsusceptible S. aureus (MSSA) isolates. We identified 11 major MRSA clones within five groups of related genotypes. The putative ancestral genotype of each group and the most parsimonious patterns of descent of isolates from each ancestor were inferred by using BURST, which, together with analysis of the methicillin resistance genes, established the likely evolutionary origins of each major MRSA clone, the genotype of the original MRSA clone and its MSSA progenitor, and the extent of acquisition and horizontal movement of the methicillin resistance genes. Major MRSA clones have arisen repeatedly from successful epidemic MSSA strains, and isolates with decreased susceptibility to vancomycin, the antibiotic of last resort, are arising from some of these major MRSA clones, highlighting a depressing progression of increasing drug resistance within a small number of ecologically successful S. aureus genotypes.

Research paper thumbnail of A framework for global surveillance of antibiotic resistance

Drug Resistance Updates, 2011

The foreseen decline in antibiotic effectiveness explains the needs for data to inform the global... more The foreseen decline in antibiotic effectiveness explains the needs for data to inform the global public health agenda about the magnitude and evolution of antibiotic resistance as a serious threat to human health and development. Opportunistic bacterial pathogens are the cause of the majority of community and hospital-acquired infections worldwide. We provide an inventory of pre-existing regional surveillance programs in the six WHO regions which should form the underpinning for the consolidation of a global network infrastructure and we outline the structural components such as an international network of reference laboratories that need to be put in place to address the void of these crucial data. In addition we suggest to make use of existing Health and Demographic Surveillance Sites (HDSS) to obtain crucial information from communities in resource limited settings at household level in low-and middleincome countries in Asia and Africa. For optimising the use of surveillance data for public health action i.e. priority setting for new drug development, comparative quantification of antibiotic effectiveness at local, national, regional and global level and identification of the action gaps can be helpful.

Research paper thumbnail of Multicenter evaluation of epidemiological typing of methicillin-resistant Staphylococcus aureus strains by repetitive-element PCR analysis

Journal of clinical …, 2000

Rapid and efficient epidemiologic typing systems would be useful to monitor transmission of methi... more Rapid and efficient epidemiologic typing systems would be useful to monitor transmission of methicillin-resistant Staphylococcus aureus (MRSA) at both local and interregional levels. To evaluate the intralaboratory performance and interlaboratory reproducibility of three ...