[Show abstract][Hide abstract] ABSTRACT: In the early 2000s, a particular MRSA clonal complex (CC398) was found mainly in pigs and pig farmers in Europe. Since then, CC398 has been detected among a wide variety of animal species worldwide. We investigated the population structure of CC398 through mutation discovery at 97 genetic housekeeping loci, which are distributed along the CC398 chromosome within 195 CC398 isolates, collected from various countries and host species, including humans. Most of the isolates in this collection were received from collaborating microbiologists, who had preserved them over years. We discovered 96 bi-allelic polymorphisms, and phylogenetic analyses revealed that an epidemic sub-clone within CC398 (dubbed 'clade (C)') has spread within and between equine hospitals, where it causes nosocomial infections in horses and colonises the personnel. While clade (C) was strongly associated with S. aureus from horses in veterinary-care settings (p = 2×10(-7)), it remained extremely rare among S. aureus isolates from human infections.
PLoS ONE 02/2014; 9(2):e88083. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Methicillin-susceptible Staphylococcus aureus (MSSA) attributed to clonal complex (CC) 398 and exhibiting spa-type t571 received attention in Europe and in the USA for being associated with severe infections in humans. As this spa-type is exhibited by livestock-associated (LA) Methicillin-resistant S. aureus (MRSA) as well, it is important to discriminate LA- and human-derived strains by easy to perform, PCR-based methods. MSSA t571 contain phage int3 carrying scn and chp, whereas LA-MRSA t571 lack these markers. In contrast, pathogenicity island SaPIbov5 (detected by PCR bridging vwbbov and scn) is contained by LA-MRSA t571 and absent in the human MSSA subpopulation. Furthermore, MSSA t571 contain erm(T), the particular genomic arrangement of which was assessed by a PCR bridging erm(T) and the adjacent transposase gene. MSSA t571 are rare so far in Germany among isolates from infections in humans (0.14%) as well as among isolates from nasal colonization (0.13%). LA-MRSA t571 are also infrequent among MRSA isolated from carriage at admission to hospitals (0.1%) and also among isolates from infections in humans (0.013%).
PLoS ONE 12/2013; 8(12):e83165. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Livestock-associated Staphylococcus aureus (LA-MRSA) are mainly associated with the clonal complex (CC) 398. Although having its main reservoir as MRSA in livestock such as pigs, poultry or cattle LA-MRSA CC398 has no pronounced host specificity and can colonize or infect other animals such as horses and dogs and also humans. In German conventional farming systems nasal colonization of the animals and of humans occupationally exposed to them (up to 86%) are frequent. Further human-to-human dissemination in households occurs more rarely in general (∼4% of humans living on farms but without occupational exposition). Nasal colonization with LA-MRSA of humans at hospital admission is found in 0.08-0.2% for Germany in general. However, this proportion is higher in areas with a high density of livestock production such as in northwestern North Rhine-Westphalia or Lower Saxony. LA-MRSA CC398 is not less pathogenic for humans than S. aureus in general. Hence, LA-MRSA accounts for ∼15% of all MRSA isolates from deep-seated skin and soft-tissue infections in the community and for about 0.8-2% of all MRSA isolated from clinical specimens obtained in hospital settings. When introduced into the hospital it can cause postoperative wound infections and even septicemia. Differently from hospital-associated MRSA clones, LA-MRSA CC398 has obviously limited capacity to spread in the nosocomial setting so far (proportion of ∼1.8% among MRSA from nosocomial infections, the proportion among MRSA from blood cultures is ∼1%).
International journal of medical microbiology: IJMM 04/2013; · 4.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: We investigated the population structure of Staphylococcus aureus clonal complex CC121 by mutation discovery at 115 genetic housekeeping loci from each of 154 isolates, sampled on five continents between 1953 and 2009. In addition, we pyro-sequenced the genomes from ten representative isolates. The genome-wide SNPs that were ascertained revealed the evolutionary history of CC121, indicating at least six major clades (A to F) within the clonal complex and dating its most recent common ancestor to the pre-antibiotic era. The toxin gene complement of CC121 isolates was correlated with their SNP-based phylogeny. Moreover, we found a highly significant association of clinical phenotypes with phylogenetic affiliations, which is unusual for S. aureus. All isolates evidently sampled from superficial infections (including staphylococcal scalded skin syndrome, bullous impetigo, exfoliative dermatitis, conjunctivitis) clustered in clade F, which included the European epidemic fusidic-acid resistant impetigo clone (EEFIC). In comparison, isolates from deep-seated infections (abscess, furuncle, pyomyositis, necrotizing pneumonia) were disseminated in several clades, but not in clade F. Our results demonstrate that phylogenetic lineages with distinct clinical properties exist within an S. aureus clonal complex, and that SNPs serve as powerful discriminatory markers, able to identify these lineages. All CC121 genomes harboured a 41-kilobase prophage that was dissimilar to S. aureus phages sequenced previously. Community-associated MRSA and MSSA from Cambodia were extremely closely related, suggesting this MRSA arose in the region.
PLoS ONE 03/2013; 8(3):e58155. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Nosocomial infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are a problem in hospital settings worldwide. The National Reference Centre for Staphylococci performs molecular typing on a representative sample set of MRSA isolates from German hospitals for assessing long-term trends thus following the dynamics of emergence and spread of MRSA clones. The article focuses on recent data concerning antibiotic resistance and epidemic MRSA in nosocomial settings and also reflects the impact of community-acquired MRSA and MRSA from zoonotic reservoirs. Identifying common and newly emerging clones is an on-going challenge in the changing epidemiology of MRSA and prevention of further spread needs molecular surveillance.
[Show abstract][Hide abstract] ABSTRACT: Since the relationship between dogs and their owners has changed, and dogs moved from being working dogs to family members in post-industrial countries, we hypothesized that zoonotic transmission of opportunistic pathogens like coagulase positive staphylococci (CPS) is likely between dogs and their owners.
CPS- nasal carriage, different aspects of human-to-dog relationship as well as potential interspecies transmission risk factors were investigated by offering nasal swabs and a questionnaire to dog owners (108) and their dogs (108) at a dog show in 2009. S. aureus was found in swabs of 20 (18.5%) humans and two dogs (1.8%), and spa types which correspond to well known human S. aureus lineages dominated (e.g. CC45, CC30 and CC22). Multilocus sequence typing (MLST) of the two canine strains revealed ST72 and ST2065 (single locus variant of ST34). Fifteen dogs (13.9%) and six owners (5.6%) harboured S. pseudintermedius, including one mecA-positive human isolate (MRSP). Pulsed field gel electrophoresis (PFGE) revealed that one dog/owner pair harboured indistinguishable S. pseudintermedius- isolates of ST33. Ten (48%) of the 21 S. pseudintermedius-isolates showed resistance towards more than one antimicrobial class. 88.9% of the dog owners reported to allow at least one dog into the house, 68.5% allow the dog(s) to rest on the sofa, 39.8% allow their dogs to come onto the bed, 93.5% let them lick their hands and 52.8% let them lick their face. Bivariate analysis of putative risk factors revealed that dog owners who keep more than two dogs have a significantly higher chance of being colonized with S. pseudintermedius than those who keep 1-2 dogs (p<0.05).
In conclusion, CPS transmission between dog owners and their dogs is possible. Further investigation regarding interspecies transmission and the diverse adaptive pathways influencing the epidemiology of CPS (including MRSA and MRSP) in different hosts is needed.
PLoS ONE 04/2012; 7(4):e35197. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) ST398 isolated from pigs raised in conventional farms was previously reported. Here we report a study on 25 farms adhering to an alternative system. LA-MRSA ST398 was not detected in nasal swabs from 178 pigs or from 89 humans working and living on these farms.
Applied and Environmental Microbiology 12/2011; 78(4):1296-7. · 3.95 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: MRSA CC130 containing the mecA homologue mecA(LGA251) were reported from the UK and from Denmark so far from cattle and humans. Here we report on 11 MRSA CC130 among a sample of 12691 isolates of human origin collected from January 2006 until June 2011. MRSA CC130 grew insufficiently on chromogernic agar plates for detection of MRSA; the agglutination test for presence of PBP2a was negative. We designed primers for specific detection of mecA(LGA251) as well as for concomitant detection of both, mec(LGA251) and mecA. As already described, the isolates exhibited spa-types t843, t1736, and t1773. The ccrA homologue indicated the presence SCCmec(XI). When subjected to further characterization by means of a commercially available microarray the isolates were negative for sak chp, and scn, and as expected positive for hla, untruncated hlb, and hld. They furthermore contained edinB, aur, slpA, slpB, slpE. From genes coding for surface and cell wall associated products the ica-operon, cap8, clfA, clfF, ebpS, fnbA, fnbB, sdrC were detected but not cna. The isolates were negative for enterotoxin genes and tst, as well as for eta, and etb; agr-type was III.
PLoS ONE 09/2011; 6(9):e24360. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In staphylococci, methylation of A2503 of 23S rRNA leads to resistance against several classes of antibiotics (oxazolidinones, phenicols, streptogramin compounds, lincosamidins and pleuromutilins). The corresponding resistance gene cfr is located on plasmid(s) and is transferable within and between staphylococcal species including Staphylococcus aureus. It first emerged in coagulase-negative staphylococci, later in Central Europe also in S. aureus ST9 and in methicillin-resistant S. aureus ST398, which have their main reservoir in pigs, and meanwhile also in nosocomial coagulase-negative staphylococci from Southern Europe and the USA, and furthermore in nosocomial methicillin-resistant S. aureus in Spain. Timely detection and targeted prevention of further dissemination in both human and veterinary medicine is warranted for preserving the activity linezolid as an important antibiotic for treatment of staphylococcal infections.
[Show abstract][Hide abstract] ABSTRACT: To estimate the proportion of methicillin-resistant Staphylococcus aureus (MRSA) isolates from humans that were sequence type (ST) 398, we surveyed 24 laboratories in 17 countries in Europe in 2007. Livestock-associated MRSA ST398 accounted for only a small proportion of MRSA isolates from humans; most were from the Netherlands, Belgium, Denmark, and Austria.
[Show abstract][Hide abstract] ABSTRACT: The emergence of methicillin-resistant Staphylococcus aureus (MRSA) in animals such as horses, pet animals and productive livestock has raised questions of a probable human origin and in more general of host specificity of S. aureus. Particular clonal lineages are obviously specific for humans (e.g. ST15, ST25, ST45) and other for ruminants (e.g. ST151). MRSA associated with veterinary nosocomial infections (e.g. ST8 and ST254 in horses, ST22 in small animals) very likely have their origin in health care facilities. MRSA ST398 which became first known from widespread colonization in industrially raised pigs seems to have a limited host specificity and is able to colonize and to cause infections in various hosts. Mechanisms of host adaptation and their genomic background are poorly understood so far.
International journal of medical microbiology: IJMM 12/2009; 300(2-3):109-17. · 4.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Studies in several European countries and in North America revealed a frequent nasal colonization of livestock with MRSA CC398 and also in humans with direct professional exposure to colonized animals. The study presented here addresses the question of further transmission to non exposed humans.
After selecting 47 farms with colonized pigs in different regions of Germany we sampled the nares of 113 humans working daily with pigs and of their 116 non exposed family members. The same was performed in 18 veterinarians attending pig farms and in 44 of their non exposed family members. For investigating transmission beyond families we samples the nares of 462 pupils attending a secondary school in a high density pig farming area. MRSA were detected by direct culture on selective agar. The isolates were typed by means of spa-sequence typing and classification of SCCmec elements. For attribution of spa sequence types to clonal lineages as defined by multi locus sequence typing we used the BURP algorithm. Antibiotic susceptibility testing was performed by microbroth dilution assay.
At the farms investigated 86% of humans exposed and only 4.3% of their family members were found to carry MRSA exhibiting spa-types corresponding to clonal complex CC398. Nasal colonization was also found in 45% of veterinarians caring for pig farms and in 9% of their non exposed family members. Multivariate analysis revealed that antibiotic usage prior to sampling beard no risk with respect to colonization. From 462 pupils only 3 were found colonized, all 3 were living on pig farms.
These results indicate that so far the dissemination of MRSA CC398 to non exposed humans is infrequent and probably does not reach beyond familial communities.
PLoS ONE 02/2009; 4(8):e6800. · 3.53 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Methicillin-resistant Staphylococcus aureus clonal lineage ST398 and methicillin-susceptible lineage ST9 strains have their main reservoir in swine but can colonize and cause infections in humans. The phenicol/lincosamide/oxazolidinone/pleuromutilin/streptogramin A multidrug resistance gene cfr was detected in isolates of both clonal lineages, rendering a spread to humans with exposure to swine farming possible.
Antimicrobial Agents and Chemotherapy 01/2009; 53(2):779-81. · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: During 2006 and 2007 small clusters of methicillin-resistant Staphylococcus aureus (MRSA) infections in horses were recorded in different clinical departments of a veterinary university. The infections were caused by different MRSA clones (ST1, ST254, and ST398). In the same time, nasal colonization of veterinarians, veterinary personnel, and students was observed indicating transmission to humans.
[Show abstract][Hide abstract] ABSTRACT: Development of multiple resistances to antibiotics in staphylococci, enterococci and pneumococci became a health threat during the past 20 years, not only with respect to nosocomial infections. This resistance development is based on acquisition of resistance genes by predominant epidemic subpopulations (clonal complexes). Although emergence and spread of methicillin-resistant Staphylococcus aureus is associated with a limited number of epidemic clones which have been widely disseminated, acquisition of SCCmec elements by susceptible ancestors has taken place at different times and at different locations. Among Staphylococcus epidermidis and Enterococcus faecium, one clonal complex, which had acquired resistance genes at several occasions, is widely disseminated in hospitals. Also in Streptococcus pneumoniae, antibiotic resistance is preferentially associated with clonal lineages which have a capacity for spreading. They became, however, more rare after introduction of the 7-valent conjugate vaccine.
International journal of medical microbiology: IJMM 08/2008; 298(5-6):365-77. · 4.54 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In 2007, 678 pigs of all age groups out of 347 different farms from Lower Saxony and Northrhine-Westphalia and 86 persons occupationally exposed to pigs were investigated for their nasal colonisation with methicillin-resistant Staphylococcus areus (MRSA) by the Field Station for Epidemiology of the University of Veterinary Medicine Hannover and the Robert Koch-Institute. At the individual animal level, a frequency of positive results of 13% (n = 85 positive animals) and at the herd level, a frequency of positive results of 18% (n = 62 positive herds) were found. All isolates were assigned to the Multilocus Sequence Typing Type ST398. Within MRSA-positive herds, there were more MRSA-negative than MRSA-positive animals. Among the occupationally exposed persons (veterinarians, laboratory personnel and meat inspection personnel), 20 persons (23%) showed a nasal colonisation with MRSA ST398. A quite strong association between the intensity of the contact to pigs with the frequency of nasal colonisation in the occupationally exposed persons was detected. None of the animals or the humans nasally colonised by MRSA ST398 showed any clinical symptoms of a staphylococcal infection. Conclusions are drawn on the herd and intra-herd prevalence of the nasal colonisation of pigs with MRSA ST398 in pigs, but especially on which questions need to be addressed by further research.
DTW. Deutsche tierärztliche Wochenschrift 05/2008; 115(4):132-9. · 0.41 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Detection of low-level oxacillin-resistant Staphylococcus aureus is a problem that needs special attention, particularly in relation to methicillin-resistant S. aureus (MRSA) strains in the community that belong to clonal lineage ST80. This study compared different phenotypic methods for the detection of 74 low-level oxacillin-resistant S. aureus strains (oxacillin MIC <or=1 mg/L), 46 MRSA strains (oxacillin MIC >or=2 mg/L) and 117 methicillin-susceptible S. aureus strains. Determination of microbroth dilution MICs for oxacillin was wholly unsatisfactory, and gave a limited specificity for cefoxitin. The sensitivity of disk-diffusion performed according to CLSI recommendations was 92% with an oxacillin 1-microg disk, and 96% with a cefoxitin 30-microg disk; use of a 10-microg cefoxitin disk and a semi-confluent inoculum (breakpoint for resistance <18 mm zone diameter) gave a sensitivity of 97%. When disk-diffusion was performed on IsoSensitest agar with a zone diameter breakpoint for resistance of <22 mm (as recommended by the Swedish Reference Group for Antibiotics), the sensitivity was 95%.
Clinical Microbiology and Infection 04/2007; 13(4):408-12. · 5.20 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Methicillin-resistant Staphylococcus aureus of clonal lineage ST398 that exhibits related spa types and contains SCCmec elements of types IVa or V has been isolated from colonized and infected humans and companion animals (e.g., dog, pig, horse) in Germany and Austria. Of particular concern is the association of these cases with cases of nosocomial ventilator-associated pneumonia.