The Emergence of Mupirocin Resistance among Clinical Isolates of Methicillin-Resistant Staphylococcus aureus in Trinidad: a First Report.
Jpn J Infect Dis. 2008 Mar
Orrett FA.
Unit of Pathology and Microbiology, Faculty of Medical Sciences, The University of the West Indies, St. Augustine, Trinidad and Tobago, West Indies. drfao4301@yahoo.com.
The objective of the study was to investigate the trend of mupirocin resistance among methicillin-resistant Staphylococcus aureus (MRSA) in Trinidad. No premarketing susceptibility surveillance was ever done following the introduction of mupirocin in 1986. A total of 188 MRSA strains recovered over a 2-year period from various body sites were tested for mupirocin resistance via the disc diffusion method. The major sources of MRSA were surgical site infections (74.0%) and bloodstream infections (8.0%). High-level and low-level mupirocin resistance were detected in 26.1 and 44.1% of MRSA stains, respectively. Resistances to other non-beta-lactam antibiotics were also high. Ninety-eight percent of all MRSA were resistant to erythromycin. This was followed by resistance rates of 96.8, 95.2, 94.1, 93.6, and 93.1%, for gentamicin, ciprofloxacin, amikacin and tobramycin, co-trimoxazole, and tetracycline, respectively. No MRSA strains were found to be resistant to vancomycin, linezolid, and quinupristin-dalfopristin. The study showed that mupirocin resistance among Trinidadian MRSA strains was relatively high compared to that seen in other countries. Because of the increasing prevalence of MRSA at the San Fernando General Hospital (SFGH) and the apparently increasing resistance to mupirocin, frequent monitoring of MRSA susceptibility patterns and infection control initiatives may be helpful in reducing the incidence of MRSA with a concomitant decrease in mupirocin resistance. This report is the first after 20 years of continuous use of the drug at the SFGH.
Japanese Journal of Infectious Disease
Thursday, March 27, 2008
Sunday, March 23, 2008
Long-term outcomes following infection with meticillin-resistant or meticillin-susceptible Staphylococcus aureus.
Long-term outcomes following infection with meticillin-resistant or meticillin-susceptible Staphylococcus aureus.
J Hosp Infect. 2008 Mar
Haessler S, Mackenzie T, Kirkland KB.
Dartmouth–Hitchcock Medical Center, Dartmouth Medical School, Lebanon, New Hampshire, USA.
Staphylococcus aureus (SA) is becoming increasingly resistant to antibiotics in hospitals and the community. Long-term outcomes following susceptible and resistant SA infection have not been studied. We performed a retrospective matched pair analysis of all patients with positive culture for meticillin-resistant SA (MRSA) or meticillin-susceptible SA (MSSA) from any site to assess the outcomes of infection. Data were collected for length of hospitalisation and in-hospital mortality, as well as longer-term outcomes including all-cause mortality, number of rehospitalisations and subsequent cultures for SA during the year following infection. Twelve months after their initial SA infection, 42% of patients were dead. There were no differences between the groups in short-term mortality, length of hospitalisation, number of subsequent hospitalisations and cultures for SA during the year following infection.
Following discharge, however, MRSA infection was associated with higher mortality than MSSA at three months (32% vs 18% P=0.02), six months (42% vs 22% P=0.002) and 12 months (51% vs 32% P=0.005). In conclusion, SA infection is associated with a high one-year all-cause mortality. Most deaths occur after discharge. The likelihood of dying during the year following infection is higher for patients with MRSA infection than for those with MSSA infection.
Elsevier
J Hosp Infect. 2008 Mar
Haessler S, Mackenzie T, Kirkland KB.
Dartmouth–Hitchcock Medical Center, Dartmouth Medical School, Lebanon, New Hampshire, USA.
Staphylococcus aureus (SA) is becoming increasingly resistant to antibiotics in hospitals and the community. Long-term outcomes following susceptible and resistant SA infection have not been studied. We performed a retrospective matched pair analysis of all patients with positive culture for meticillin-resistant SA (MRSA) or meticillin-susceptible SA (MSSA) from any site to assess the outcomes of infection. Data were collected for length of hospitalisation and in-hospital mortality, as well as longer-term outcomes including all-cause mortality, number of rehospitalisations and subsequent cultures for SA during the year following infection. Twelve months after their initial SA infection, 42% of patients were dead. There were no differences between the groups in short-term mortality, length of hospitalisation, number of subsequent hospitalisations and cultures for SA during the year following infection.
Following discharge, however, MRSA infection was associated with higher mortality than MSSA at three months (32% vs 18% P=0.02), six months (42% vs 22% P=0.002) and 12 months (51% vs 32% P=0.005). In conclusion, SA infection is associated with a high one-year all-cause mortality. Most deaths occur after discharge. The likelihood of dying during the year following infection is higher for patients with MRSA infection than for those with MSSA infection.
Elsevier
Thursday, March 20, 2008
A model for surveillance of methicillin-resistant Staphylococcus aureus
A model for surveillance of methicillin-resistant Staphylococcus aureus
Public Health Rep. 2008 Jan-Feb
Simons H, Alcabes P.
Hunter College, City University of New York, School of Health Sciences, New York, NY 10010, USA.
It is well recognized that methicillin-resistant Staphylococcus aureus (MRSA) has become a community pathogen. Several key differences between community-associated and hospital-associated MRSA strains exist, including distinct methicillin resistance genes and genetic backgrounds and differing susceptibility to antibiotics. Recent studies have demonstrated that typical hospital and community strains easily move between hospital and community environments. Despite evidence of MRSA's expanding reach in the community, the best methods for population-level detection and containment have not been established. In an effort to determine effective methods for monitoring the spread of MRSA, we reviewed the literature on hospital-associated and community-associated MRSA (CA-MRSA) in the community and proposed a model for enhanced surveillance. By linking epidemiologic and molecular techniques within a surveillance system that coordinates activities in the community and health-care setting, scientists and public health officials can begin to measure the true extent of CA-MRSA in communities and hospitals.
PubMed
Public Health Rep. 2008 Jan-Feb
Simons H, Alcabes P.
Hunter College, City University of New York, School of Health Sciences, New York, NY 10010, USA.
It is well recognized that methicillin-resistant Staphylococcus aureus (MRSA) has become a community pathogen. Several key differences between community-associated and hospital-associated MRSA strains exist, including distinct methicillin resistance genes and genetic backgrounds and differing susceptibility to antibiotics. Recent studies have demonstrated that typical hospital and community strains easily move between hospital and community environments. Despite evidence of MRSA's expanding reach in the community, the best methods for population-level detection and containment have not been established. In an effort to determine effective methods for monitoring the spread of MRSA, we reviewed the literature on hospital-associated and community-associated MRSA (CA-MRSA) in the community and proposed a model for enhanced surveillance. By linking epidemiologic and molecular techniques within a surveillance system that coordinates activities in the community and health-care setting, scientists and public health officials can begin to measure the true extent of CA-MRSA in communities and hospitals.
PubMed
Friday, March 14, 2008
Methicillin-Resistant Staphylococcus aureus in a Family and Its Pet Cat
Methicillin-Resistant Staphylococcus aureus in a Family and Its Pet Cat
NEJM Mar 13, 2008
To the Editor: Many isolates of community-acquired methicillin-resistant Staphylococcus aureus (MRSA) produce Panton–Valentine leukocidin (PVL), increasing the virulence of the bacteria, which can cause disseminated deep abscesses and necrotizing pneumonia.1 We report the transmission of PVL-positive MRSA between a symptomatic woman and both her asymptomatic family and their healthy pet cat.
An otherwise healthy woman presented with recurrent multiple deep abscesses. Swabs from several abscesses and nasal cultures grew MRSA that was resistant to both beta-lactam and fusidic acid antibiotics. Polymerase-chain-reaction assays for the PVL genes lukS-PV and lukF-PV were positive. The genotype of the staphylococcal chromosomal cassette was SCCmec type IV. Nasal, axillary, and inguinal cultures from her husband and their two children yielded MRSA on several occasions. Mupirocin nasal ointment and antiseptic washes were recommended for all family members. Although the patient's husband and children became MRSA-negative, the patient remained MRSA-positive. Therefore, her three apparently healthy cats were screened. Pharyngeal culture from one cat grew MRSA with the same antimicrobial resistance pattern as that of the human isolates. The clonal identity of the isolates from the family and the cats was found by typing of the spa gene repeat region and multilocus sequence typing,2,3 which showed spa-type t131 and ST80 in all isolates. This sequence combination does not correspond with that of clone USA300 (reference)
A veterinarian recommended topical decolonization of the MRSA-positive cat with ciprofloxacin and rifampin. Four weeks after the cat's treatment, screening tests of the family were negative for MRSA. Moreover, the patient's deep abscesses completely resolved. Further MRSA screening of the asymptomatic cat was declined by the family.
There is evidence that companion animals, mainly dogs, harbor MRSA,4 and interspecies MRSA transmission has been shown in the members of a family and their dog.5 This case illustrates that MRSA transmission also occurs between humans and cats. The abscesses in our patient cleared only after antibiotic treatment of the cat. It remains unclear whether the cat was the source of the patient's infection or vice versa, although spa-type t131 is extremely rare in humans.2 We conclude that pets should be considered as possible household reservoirs of MRSA that can cause infection or reinfection in humans.
Andreas Sing, M.D. Christian Tuschak, Ph.D. Stefan Hörmansdorfer, Vet.D. Bavarian Food and Health Safety Authority 85764 Oberschleißheim, Germany
New England Journal of Medicine
Woman and Cat Shared 'Super Bug'
By Serena GordonHealthDay Reporter Wed Mar 12, 11:47 PM ET
WEDNESDAY, March 12 (HealthDay News) -- People share their homes, their food and more with their pets, but one thing you probably never thought you could share with your animals is a drug-resistant staph infection.
However, according to a letter in the March 13 issue of the New England Journal of Medicine, a German family appears to have done just that. Doctors were puzzled when a woman was repeatedly treated for methicillin-resistant Staphylococcus aureus (MRSA), yet still kept coming back with the infection.
Eventually, they discovered that the family cat was harboring the dangerous bacteria, sometimes called a "super bug."
"Animals and especially pets or companion animals might serve as reservoirs for human-pathogenic bacteria," said Dr. Andreas Sing, head of the department of infectiology at the Bavarian Food and Health Safety Authority in Germany.
Before you give puss the boot, know that researchers believe it was the woman who probably initially transmitted the bacteria to the cat, not the other way around.
About 25 percent to 30 percent of Americans are colonized with staph bacteria, but only about 1 percent are colonized with MRSA, according to the U.S. Centers for Disease Control and Prevention. Most MRSA infections occur in health-care settings, such as hospitals or nursing homes, but the number of community-acquired infections is growing. According to the CDC, about 12 percent of all MRSA infections are now acquired in the community.
MRSA spreads through skin-to-skin contact with an infected person, but its transmission has also been associated with contaminated surfaces, crowded living conditions and poor hygiene, according to the CDC.
MRSA infections often look like a boil or an inflamed pimple, and may be red, swollen and draining pus, the CDC said.
The German woman was otherwise healthy, but kept getting multiple, deep abscesses. Both the abscesses and nasal swabs tested positive for MRSA. Her family members -- a husband and two children -- were also tested, and they tested positive on several occasions. Nasal ointments and antiseptic washes were prescribed for the family to "decolonize" them.
The family members then tested negative for MRSA, but the woman kept testing positive. Doctors then tested the woman's three cats, and found that one, despite having no symptoms, was carrying the same strain of MRSA. Once the cat was decolonized and both the cat and woman were retreated with antibiotics, all family members -- human and feline -- tested negative for the bacteria.
Sing and his colleagues pointed out that this is the first documented MRSA infection in a cat, although there have been reports of other animals, including dogs, harboring MRSA.
Because this infection is generally community-acquired, Sing thinks it's more likely that the woman initially transmitted the bacteria to her pet, and then the animal passed the infection back to her.
"Cats are social. They like to rub up against people and it's the skin-to-skin contact that passes MRSA," explained Dr. Matthew Sims, director of the infectious disease research program at Beaumont Hospital in Royal Oak, Mich.
But, he added, "People shouldn't start worrying about having pets. They can carry all sorts of things which we've known about forever, but you don't need to get rid of your cats or other animals."
Sims said that if you suspect you might have a MRSA infection, go to your doctor for treatment and let your doctor know if you have other people or pets in your household so your doctor can recommend appropriate treatment or prevention steps for them.
The best way to prevent these infections, Sims said, is to practice good hygiene and wash your hands frequently. If you know you have a MRSA infection, avoid direct contact with other people and animals until you've been treated.
More information
To learn more about MRSA, visit the U.S. Centers for Disease Control and Prevention.
Yahoo News
Wednesday, March 5, 2008
Community-associated methicillin-resistant Staphylococcus aureus skin infections: advances toward identifying the key virulence factors.
Community-associated methicillin-resistant Staphylococcus aureus skin infections: advances toward identifying the key virulence factors.
Curr Opin Infect Dis. 2008 Apr
Nygaard TK, Deleo FR, Voyich JM.
aDepartment of Veterinary Molecular Biology, Montana State University, Bozeman, USA bLaboratory of Human Bacterial Pathogenesis, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, NIH, Hamilton, Montana, USA.
PURPOSE OF REVIEW: In recent years there has been an increase in the incidence of community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections in healthy individuals, the cause of which is largely unknown. CA-MRSA primarily causes skin and soft-tissue infections but certain strains are also associated with unusually severe pathology. The purpose of this review is to provide a critical analysis of our current knowledge of virulence factors contributing to skin and soft-tissue infections caused by CA-MRSA.
RECENT FINDINGS: Isolates classified as pulsed-field gel electrophoresis type USA300 have emerged as the predominant CA-MRSA genotype and in most geographic areas account for 97% or more of CA-MRSA infections. Recent key studies, such as those reporting the complete genome sequence of USA300, and the discovery of cytolytic peptides that contribute significantly to CA-MRSA virulence, lead the way for future investigations.
SUMMARY: Although we have only a cursory understanding of the molecular mechanisms of CA-MRSA virulence, studies using clinically relevant CA-MRSA isolates are beginning to identify virulence determinants specific to this pathogen. Identifying CA-MRSA virulence determinants and the concerted regulation of these factors will foster development of vaccines and therapeutics designed to control CA-MRSA skin infections.
Sunday, March 2, 2008
Methicillin-Resistant and -Susceptible Staphylococcus aureus Sequence Type 398 in Pigs and Humans
Methicillin-Resistant and Susceptible Staphylococcus aureus Sequence Type 398 in Pigs and Humans
EID - Volume 14, Number 3–March 2008
Alex van Belkum,* Damian C. Melles,* Justine K. Peeters,* Willem B. van Leeuwen,* Engeline van Duijkeren,† Xander W. Huijsdens,‡ Emile Spalburg,‡ Albert J. de Neeling,‡ and Henri A. Verbrugh,* on behalf of the Dutch Working Party on Surveillance and Research of MRSA (SOM)1*University Medical Center Rotterdam, Rotterdam, the Netherlands; †University of Utrecht, Utrecht, the Netherlands; and ‡National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
Nasal Staphylococcus aureus carriage has increased in pig farmers, and specific lineages of S. aureus are shared by farmers and their animals (1,2). In addition, rates of nasal carriage of methicillin-resistant S. aureus (MRSA) by veterinary personnel working with pigs is high (3–5). The pig-related MRSA appears to be clonal and was identified by multilocus sequence typing (MLST) as sequence type 398 (2,6,7). Such resistant bacterial strains can spread from animals to the environment, which may facilitate the colonization of persons who are not involved in animal husbandry (8). The porcine MRSA strain has been isolated from humans with invasive and superficial infections, and familial outbreaks of colonization and cross-colonization have been documented (2,6,7).
We sought to determine whether the clinical effect of the porcine ST398 MRSA strain can be substantiated by the existence of genetically homologous, methicillin-susceptible S. aureus (MSSA) strains among healthy or infected persons. The international MLST database (www.mlst.net) (9) listed only 1 ST398 MSSA nasal carriage isolate from a patient in Cape Verde. In addition, 1 ST398 MRSA strain was isolated from a woman living in Groningen, the Netherlands, without further clinical and epidemiologic data available. ST398 MSSA nasal carriage isolates were also identified in several pig farmers in a study by Armand-Lefevre et al. (1). We describe the population genetic analysis of Dutch community-based and nosocomial MSSA isolates in comparison with pig- and pig farmer–derived ST398 MRSA isolates, performed by spa-sequencing and amplified fragment length polymorphism (AFLP) analysis (10,11).
The Study
Most of the ST398 MRSA strains studied were collected at the Dutch Institute for Public Health and the Environment (RIVM, Bilthoven, the Netherlands). A total of 20 strains were isolated from the nares of pigs in several slaughterhouses (RIVM 21–40) (12), whereas 18 additional strains were detected during in-hospital screenings for MRSA carriage among Dutch farmers from independent farms (RIVM 1–8, 10–12 and 14–20). In addition, 8 clinical and carriage isolates were obtained from the Veterinary Medical Diagnostic Centre in Utrecht (Table).
Amplified fragment length polymorphism (AFLP) analysis was performed as described previously (10). A total of 147 marker fragments per strain were scored, and a binary table with marker absence [0] or presence [1] was constructed. A total of 30 fragments with differential occurrence, when genetically heterogeneous MSSA and ST398 MRSA fingerprints were compared, were reamplified and sequenced (Applied Biosystems, Foster City, CA, USA). Fragments were sequenced for 3 independent strains, and the consensus was analyzed by using BLAST . Typing of the staphylococcal chromosome cassette (SCCmec) and the presence of the Panton-Valentine leukocidin (PVL) genes was performed by PCR.
We embedded the genetic fingerprints of the 46 pig-related MRSA isolates in the population structure of S. aureus as obtained before (10,11). These studies include high throughput AFLP fingerprints of 829 nonclinical S. aureus human carriage isolates and 146 and 77 (including 2 MRSA isolates) clinical isolates of human and animal origin, respectively. All carriage strains were isolated from volunteers living in the Rotterdam region, where pig farms are absent.
Sequencing of the repetitive region of the protein A gene spa was performed for all ST398 MRSA isolates (13). Data were analyzed by using the Ridom Staphtype software version 1.4 .
Analysis of the AFLP data was performed as described previously (10). Both hierarchical cluster analysis and principle component analysis were performed with Spotfire Decision Site 7.2 software. We used the Fisher exact test to compare the distribution of strain categories in different phylogenetic lineages. A 2-sided p value <0.05>
The AFLP analysis of the ST398 MRSA strains derived from human and animal sources (n = 46) indicated that these strains are highly clonal. When the AFLP patterns for the ST398 strains were included in the overall population analysis for Dutch MSSA strains from carriage and infection, the distinct cluster was still observed (Figure 1). Few Dutch MSSA strains from the Rotterdam region coclustered with the ST398 pig-related MRSA isolates (Figure 1, panel B). In total, 6 (0.6%) MSSA isolates coclustered with the ST398 MRSA isolates, of which 2 were nasal carriage isolates from healthy persons (Table). Of the 6 strains, 3 were blood culture isolates taken from 3 elderly patients. All 3 patients had nosocomial bacteremia: 1 after inflammatory aneurism of the aorta, 1 during Fournier gangrene, and the last 1 after primary ventricular fibrillation. Epidemiologic data exclude a cluster of nosocomial infections; patients were not in direct contact (data not shown).
After principle component analysis , the ST398 MRSA strains still clustered as a separate group (Figure 2). The AFLP analysis did not distinguish strains from pigs or pig farmers, and only a limited number of polymorphic AFLP fragments were seen. AFLP markers that were positive for the ST398 MRSAs and absent from the other strains, or vice versa, were sequenced. Of 30 fragments analyzed, 9 were ≈100% specific for the pig-associated strains. Another 3 fragments were present in a subset of the pig-associated strains only. Of these 12 fragments, 4 were not homologous with current entries in the GenBank database, including the 10 S. aureus full-genome sequences. Of the 12 pig-specific markers, 8 were homologous with known sequences, which suggests that these markers become pig-specific by point mutations in the AFLP primer annealing site(s) rather than by genomic rearrangement. Several of the sequences encode factors were associated with membranes or transport.
The preponderance of types t011 and t108 was confirmed by spa sequencing (12). These made up >75% of all cases. However, the other types all belonged to the same family of spa types, which suggests recent drift in the sequence motifs. The t011 types are primarily associated with SCCmec IV and IVa, whereas the t108 type is nearly fully associated with SCCmec V. This finding suggests that ST398 MRSA has arisen independently on at least 2 occasions. Finally, SCCmec III is found in association with t108, t898, t567, t034, and t571. This finding suggests promiscuous dissemination of this cassette among the ST398 MRSA. Strain RIVM-17 harbored the PVL genes. Apparently, the bacteriophage carrying these genes found its way into the porcine ST398 MRSA lineage.
Conclusions
The massive colonization of Dutch pigs with a single sequence type of MRSA was unexpected (12). Molecular strain typing was initially compromised because PFGE failed (14). Spa gene sequencing (13) showed heterogeneity in the ST398 MRSA lineage with types t011 and t108, which are closely related, covering >75% of all isolates. Hence, 1 or 2 new MRSA lineages had been discovered. We found a degree of genetic association between spa types and the presence of certain SCCmec cassettes, which suggests bacterial evolution and horizontal DNA exchange in the zoonotic reservoir.
We found that ST398 is rare among Dutch MSSA strains colonizing healthy persons (2 [0.2%] of 829 strains). However, a relatively high number of MSSA isolates homologous to the ST398 MRSA were derived from bacteremic patients (3 [2.1%] of 146; p = 0.026). These 3 bacteremia isolates were not related epidemiologically; they were isolated from different patients in different medical departments over an extended period. This finding suggests that these MSSA strains are quite virulent. The strict segregation of ST398 strains (Figure 1, panel A; Figure 2) corroborates that the strains belong to a separate biotype associated with pigs (15).
Our findings pose a warning to public health surveillance: if the ST398 MSSA virulence toward humans would be maintained within the ST398 MRSA lineage from pigs, care should be taken not to introduce this strain into humans. We consider it to be likely that ST398 MRSA from pigs is capable of causing serious infection in humans even though its primary host seems to be pigs.
Dr van Belkum is with the Department of Medical Microbiology and Infectious Diseases, University Medical Center Rotterdam, Rotterdam, the Netherlands. His research interests include MRSA.
References
Armand-Lefevre L, Ruimy R, Andremont A. Clonal comparison of Staphylococcus aureus isolates from healthy pig farmers, human controls, and pigs. Emerg Infect Dis. 2005;11:711–4.
Witte W, Strommenger B, Stanek C, Cuny C. Methicillin-resistant Staphylococcus aureus ST398 in humans and animals, Central Europe. Emerg Infect Dis. 2007;13:255–8.
Hanselman BA, Kruth SA, Rousseau J, Low DE, Willey BM, McGeer A, et al. Methicillin-resistant Staphylococcus aureus colonization in veterinary personnel. Emerg Infect Dis. 2006;12:1933–8.
Voss A, Loeffen F, Bakker J, Klaassen C, Wulf M. Methicillin-resistant Staphylococcus aureus in pig farming. Emerg Infect Dis. 2005;11:1965–6.
Wulf M, van Nes A, Eikelenboom-Boskamp A, de Vries J, Melchers W, Klaassen C, et al. Methicillin-resistant Staphylococcus aureus in veterinary doctors and students, the Netherlands. Emerg Infect Dis. 2006;12:1939–41.
Ekkelenkamp MB, Sekkat M, Carpaij N, Troelstra A, Bonten MJ. Endocarditis due to meticillin-resistant Staphylococcus aureus originating from pigs [in Dutch]. Ned Tijdschr Geneeskd. 2006;150:2442–7.
Huijsdens XW, van Dijke BJ, Spalburg E, van Santen-Verheuvel MG, Heck ME, Pluister GN, et al. Community-acquired MRSA and pig-farming. Ann Clin Microbiol Antimicrob. 2006;5:26.
Gibbs SG, Green CF, Tarwater PM, Mota LC, Mena KD, Scarpino PV. Isolation of antibiotic-resistant bacteria from the air plume downwind of a swine confined or concentrated animal feeding operation. Environ Health Perspect. 2006;114:1032–7.
Feil EJ, Enright MC. Analyses of clonality and the evolution of bacterial pathogens. Curr Opin Microbiol. 2004;7:308–13.
Melles DC, Gorkink RF, Boelens HA, Snijders SV, Peeters JK, Moorhouse MJ, et al. Natural population dynamics and expansion of pathogenic clones of Staphylococcus aureus. J Clin Invest. 2004;114:1732–40.
van Leeuwen WB, Melles DC, Alaidan A, Al-Ahdal M, Boelens HA, Snijders SV, et al. Host- and tissue-specific pathogenic traits of Staphylococcus aureus. J Bacteriol. 2005;187:4584–91.
de Neeling AJ, van den Broek MJ, Spalburg EC, van Santen-Verheuvel MG, Dam-Deisz WD, Boshuizen HC, et al. High prevalence of methicillin resistant Staphylococcus aureus in pigs. Vet Microbiol. 2007;122:366–72.
Harmsen D, Claus H, Witte W, Rothganger J, Turnwald D, Vogel U. Typing of methicillin-resistant Staphylococcus aureus in a university hospital setting by using novel software for spa repeat determination and database management. J Clin Microbiol. 2003;41:5442–8.
Bens CC, Voss A, Klaassen CH. Presence of a novel DNA methylation enzyme in methicillin-resistant Staphylococcus aureus isolates associated with pig farming leads to uninterpretable results in standard pulsed-field gel electrophoresis analysis. J Clin Microbiol. 2006;44:1875–6.
Devriese LA. A simplified system for biotyping Staphylococcus aureus strains isolated from animal species. J Appl Bacteriol. 1984;56:215–20.
CDC
EID - Volume 14, Number 3–March 2008
Alex van Belkum,* Damian C. Melles,* Justine K. Peeters,* Willem B. van Leeuwen,* Engeline van Duijkeren,† Xander W. Huijsdens,‡ Emile Spalburg,‡ Albert J. de Neeling,‡ and Henri A. Verbrugh,* on behalf of the Dutch Working Party on Surveillance and Research of MRSA (SOM)1*University Medical Center Rotterdam, Rotterdam, the Netherlands; †University of Utrecht, Utrecht, the Netherlands; and ‡National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
Nasal Staphylococcus aureus carriage has increased in pig farmers, and specific lineages of S. aureus are shared by farmers and their animals (1,2). In addition, rates of nasal carriage of methicillin-resistant S. aureus (MRSA) by veterinary personnel working with pigs is high (3–5). The pig-related MRSA appears to be clonal and was identified by multilocus sequence typing (MLST) as sequence type 398 (2,6,7). Such resistant bacterial strains can spread from animals to the environment, which may facilitate the colonization of persons who are not involved in animal husbandry (8). The porcine MRSA strain has been isolated from humans with invasive and superficial infections, and familial outbreaks of colonization and cross-colonization have been documented (2,6,7).
We sought to determine whether the clinical effect of the porcine ST398 MRSA strain can be substantiated by the existence of genetically homologous, methicillin-susceptible S. aureus (MSSA) strains among healthy or infected persons. The international MLST database (www.mlst.net) (9) listed only 1 ST398 MSSA nasal carriage isolate from a patient in Cape Verde. In addition, 1 ST398 MRSA strain was isolated from a woman living in Groningen, the Netherlands, without further clinical and epidemiologic data available. ST398 MSSA nasal carriage isolates were also identified in several pig farmers in a study by Armand-Lefevre et al. (1). We describe the population genetic analysis of Dutch community-based and nosocomial MSSA isolates in comparison with pig- and pig farmer–derived ST398 MRSA isolates, performed by spa-sequencing and amplified fragment length polymorphism (AFLP) analysis (10,11).
The Study
Most of the ST398 MRSA strains studied were collected at the Dutch Institute for Public Health and the Environment (RIVM, Bilthoven, the Netherlands). A total of 20 strains were isolated from the nares of pigs in several slaughterhouses (RIVM 21–40) (12), whereas 18 additional strains were detected during in-hospital screenings for MRSA carriage among Dutch farmers from independent farms (RIVM 1–8, 10–12 and 14–20). In addition, 8 clinical and carriage isolates were obtained from the Veterinary Medical Diagnostic Centre in Utrecht (Table).
Amplified fragment length polymorphism (AFLP) analysis was performed as described previously (10). A total of 147 marker fragments per strain were scored, and a binary table with marker absence [0] or presence [1] was constructed. A total of 30 fragments with differential occurrence, when genetically heterogeneous MSSA and ST398 MRSA fingerprints were compared, were reamplified and sequenced (Applied Biosystems, Foster City, CA, USA). Fragments were sequenced for 3 independent strains, and the consensus was analyzed by using BLAST . Typing of the staphylococcal chromosome cassette (SCCmec) and the presence of the Panton-Valentine leukocidin (PVL) genes was performed by PCR.
We embedded the genetic fingerprints of the 46 pig-related MRSA isolates in the population structure of S. aureus as obtained before (10,11). These studies include high throughput AFLP fingerprints of 829 nonclinical S. aureus human carriage isolates and 146 and 77 (including 2 MRSA isolates) clinical isolates of human and animal origin, respectively. All carriage strains were isolated from volunteers living in the Rotterdam region, where pig farms are absent.
Sequencing of the repetitive region of the protein A gene spa was performed for all ST398 MRSA isolates (13). Data were analyzed by using the Ridom Staphtype software version 1.4 .
Analysis of the AFLP data was performed as described previously (10). Both hierarchical cluster analysis and principle component analysis were performed with Spotfire Decision Site 7.2 software. We used the Fisher exact test to compare the distribution of strain categories in different phylogenetic lineages. A 2-sided p value <0.05>
The AFLP analysis of the ST398 MRSA strains derived from human and animal sources (n = 46) indicated that these strains are highly clonal. When the AFLP patterns for the ST398 strains were included in the overall population analysis for Dutch MSSA strains from carriage and infection, the distinct cluster was still observed (Figure 1). Few Dutch MSSA strains from the Rotterdam region coclustered with the ST398 pig-related MRSA isolates (Figure 1, panel B). In total, 6 (0.6%) MSSA isolates coclustered with the ST398 MRSA isolates, of which 2 were nasal carriage isolates from healthy persons (Table). Of the 6 strains, 3 were blood culture isolates taken from 3 elderly patients. All 3 patients had nosocomial bacteremia: 1 after inflammatory aneurism of the aorta, 1 during Fournier gangrene, and the last 1 after primary ventricular fibrillation. Epidemiologic data exclude a cluster of nosocomial infections; patients were not in direct contact (data not shown).
After principle component analysis , the ST398 MRSA strains still clustered as a separate group (Figure 2). The AFLP analysis did not distinguish strains from pigs or pig farmers, and only a limited number of polymorphic AFLP fragments were seen. AFLP markers that were positive for the ST398 MRSAs and absent from the other strains, or vice versa, were sequenced. Of 30 fragments analyzed, 9 were ≈100% specific for the pig-associated strains. Another 3 fragments were present in a subset of the pig-associated strains only. Of these 12 fragments, 4 were not homologous with current entries in the GenBank database, including the 10 S. aureus full-genome sequences. Of the 12 pig-specific markers, 8 were homologous with known sequences, which suggests that these markers become pig-specific by point mutations in the AFLP primer annealing site(s) rather than by genomic rearrangement. Several of the sequences encode factors were associated with membranes or transport.
The preponderance of types t011 and t108 was confirmed by spa sequencing (12). These made up >75% of all cases. However, the other types all belonged to the same family of spa types, which suggests recent drift in the sequence motifs. The t011 types are primarily associated with SCCmec IV and IVa, whereas the t108 type is nearly fully associated with SCCmec V. This finding suggests that ST398 MRSA has arisen independently on at least 2 occasions. Finally, SCCmec III is found in association with t108, t898, t567, t034, and t571. This finding suggests promiscuous dissemination of this cassette among the ST398 MRSA. Strain RIVM-17 harbored the PVL genes. Apparently, the bacteriophage carrying these genes found its way into the porcine ST398 MRSA lineage.
Conclusions
The massive colonization of Dutch pigs with a single sequence type of MRSA was unexpected (12). Molecular strain typing was initially compromised because PFGE failed (14). Spa gene sequencing (13) showed heterogeneity in the ST398 MRSA lineage with types t011 and t108, which are closely related, covering >75% of all isolates. Hence, 1 or 2 new MRSA lineages had been discovered. We found a degree of genetic association between spa types and the presence of certain SCCmec cassettes, which suggests bacterial evolution and horizontal DNA exchange in the zoonotic reservoir.
We found that ST398 is rare among Dutch MSSA strains colonizing healthy persons (2 [0.2%] of 829 strains). However, a relatively high number of MSSA isolates homologous to the ST398 MRSA were derived from bacteremic patients (3 [2.1%] of 146; p = 0.026). These 3 bacteremia isolates were not related epidemiologically; they were isolated from different patients in different medical departments over an extended period. This finding suggests that these MSSA strains are quite virulent. The strict segregation of ST398 strains (Figure 1, panel A; Figure 2) corroborates that the strains belong to a separate biotype associated with pigs (15).
Our findings pose a warning to public health surveillance: if the ST398 MSSA virulence toward humans would be maintained within the ST398 MRSA lineage from pigs, care should be taken not to introduce this strain into humans. We consider it to be likely that ST398 MRSA from pigs is capable of causing serious infection in humans even though its primary host seems to be pigs.
Dr van Belkum is with the Department of Medical Microbiology and Infectious Diseases, University Medical Center Rotterdam, Rotterdam, the Netherlands. His research interests include MRSA.
References
Armand-Lefevre L, Ruimy R, Andremont A. Clonal comparison of Staphylococcus aureus isolates from healthy pig farmers, human controls, and pigs. Emerg Infect Dis. 2005;11:711–4.
Witte W, Strommenger B, Stanek C, Cuny C. Methicillin-resistant Staphylococcus aureus ST398 in humans and animals, Central Europe. Emerg Infect Dis. 2007;13:255–8.
Hanselman BA, Kruth SA, Rousseau J, Low DE, Willey BM, McGeer A, et al. Methicillin-resistant Staphylococcus aureus colonization in veterinary personnel. Emerg Infect Dis. 2006;12:1933–8.
Voss A, Loeffen F, Bakker J, Klaassen C, Wulf M. Methicillin-resistant Staphylococcus aureus in pig farming. Emerg Infect Dis. 2005;11:1965–6.
Wulf M, van Nes A, Eikelenboom-Boskamp A, de Vries J, Melchers W, Klaassen C, et al. Methicillin-resistant Staphylococcus aureus in veterinary doctors and students, the Netherlands. Emerg Infect Dis. 2006;12:1939–41.
Ekkelenkamp MB, Sekkat M, Carpaij N, Troelstra A, Bonten MJ. Endocarditis due to meticillin-resistant Staphylococcus aureus originating from pigs [in Dutch]. Ned Tijdschr Geneeskd. 2006;150:2442–7.
Huijsdens XW, van Dijke BJ, Spalburg E, van Santen-Verheuvel MG, Heck ME, Pluister GN, et al. Community-acquired MRSA and pig-farming. Ann Clin Microbiol Antimicrob. 2006;5:26.
Gibbs SG, Green CF, Tarwater PM, Mota LC, Mena KD, Scarpino PV. Isolation of antibiotic-resistant bacteria from the air plume downwind of a swine confined or concentrated animal feeding operation. Environ Health Perspect. 2006;114:1032–7.
Feil EJ, Enright MC. Analyses of clonality and the evolution of bacterial pathogens. Curr Opin Microbiol. 2004;7:308–13.
Melles DC, Gorkink RF, Boelens HA, Snijders SV, Peeters JK, Moorhouse MJ, et al. Natural population dynamics and expansion of pathogenic clones of Staphylococcus aureus. J Clin Invest. 2004;114:1732–40.
van Leeuwen WB, Melles DC, Alaidan A, Al-Ahdal M, Boelens HA, Snijders SV, et al. Host- and tissue-specific pathogenic traits of Staphylococcus aureus. J Bacteriol. 2005;187:4584–91.
de Neeling AJ, van den Broek MJ, Spalburg EC, van Santen-Verheuvel MG, Dam-Deisz WD, Boshuizen HC, et al. High prevalence of methicillin resistant Staphylococcus aureus in pigs. Vet Microbiol. 2007;122:366–72.
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Bens CC, Voss A, Klaassen CH. Presence of a novel DNA methylation enzyme in methicillin-resistant Staphylococcus aureus isolates associated with pig farming leads to uninterpretable results in standard pulsed-field gel electrophoresis analysis. J Clin Microbiol. 2006;44:1875–6.
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CDC
Saturday, March 1, 2008
Prostatic Abscess Due to Community-Acquired Methicillin-Resistant Staphylococcus aureus.
Prostatic Abscess Due to Community-Acquired Methicillin-Resistant Staphylococcus aureus.
Am J Med Sci. 2008 Feb
Pierce JR Jr, Saeed Q, Davis WR.
From the Department of Internal Medicine, Texas Tech University Health Sciences Center, Amarillo, Texas; and the Veterans Administration Medical Center, Amarillo, Texas.
Am J Med Sci. 2008 Feb
Pierce JR Jr, Saeed Q, Davis WR.
From the Department of Internal Medicine, Texas Tech University Health Sciences Center, Amarillo, Texas; and the Veterans Administration Medical Center, Amarillo, Texas.
We report what we believe to be the second case of a prostatic abscess due to community-acquired methicillin-resistant Staphylococcus aureus (MRSA). A previously healthy diabetic man presented with dysuria, fatigue, weight loss, a tender prostate, and leukocytosis. Computerized tomography of the abdomen and pelvis demonstrated a large prostatic abscess at the base of the bladder. Blood, urine, and pus obtained by percutaneous aspiration grew MRSA. Percutaneous drainage and prolonged therapy with intravenous vancomycin resulted in cure. Prostatic abscess is most often caused by Gram-negative organisms. Community-acquired MRSA, which usually causes skin and soft tissue infections, may also cause prostatic abscess. The mainstay of treatment of prostatic abscess is drainage, which can be accomplished either percutaneously or transurethrally. Gram stain and culture of the drainage will direct proper antibiotic selection.
Lippincott, Williams & Wilkins
Lemierre's Syndrome: Methicillin-Resistant Staphylococcus aureus (MRSA) Finds a New Home.
Lemierre's Syndrome: Methicillin-Resistant Staphylococcus aureus (MRSA) Finds a New Home.
J Emerg Med. 2008 Feb
Bentley TP, Brennan DF.
Department of Emergency Medicine, Emergency Medicine Residency Program, Orlando Regional Medical Center, Orlando, Florida.
Lemierre's syndrome is septic thrombophlebitis of the internal jugular vein, arising as a complication of an oropharyngeal infection. This thrombophlebitis frequently results in septic emboli to organs such as the lungs. The causative agent in most previously described cases is Fusobacterium necrophorum, an anaerobic Gram-negative organism. We present the case of an 8-year-old previously healthy girl who came to the Emergency Department with a 5-day history of left-sided neck pain and was subsequently diagnosed with methicillin-resistant Staphylococcus aureus (MRSA) Lemierre's syndrome. MRSA has not previously been described in Lemierre's syndrome in the Emergency Medicine literature. The clinical presentation, findings, and management of the syndrome are discussed. Regardless of etiology, once the diagnosis of Lemierre's syndrome is made, long-term broad-spectrum intravenous therapy will be necessary.
Elsevier Science Direct
J Emerg Med. 2008 Feb
Bentley TP, Brennan DF.
Department of Emergency Medicine, Emergency Medicine Residency Program, Orlando Regional Medical Center, Orlando, Florida.
Lemierre's syndrome is septic thrombophlebitis of the internal jugular vein, arising as a complication of an oropharyngeal infection. This thrombophlebitis frequently results in septic emboli to organs such as the lungs. The causative agent in most previously described cases is Fusobacterium necrophorum, an anaerobic Gram-negative organism. We present the case of an 8-year-old previously healthy girl who came to the Emergency Department with a 5-day history of left-sided neck pain and was subsequently diagnosed with methicillin-resistant Staphylococcus aureus (MRSA) Lemierre's syndrome. MRSA has not previously been described in Lemierre's syndrome in the Emergency Medicine literature. The clinical presentation, findings, and management of the syndrome are discussed. Regardless of etiology, once the diagnosis of Lemierre's syndrome is made, long-term broad-spectrum intravenous therapy will be necessary.
Elsevier Science Direct
Should the Currently Recommended Twice-Daily Dosing Still be Considered the Most Appropriate Regimen for Treating MRSA Ventilator-Associated Pneumonia
Should the Currently Recommended Twice-Daily Dosing Still be Considered the Most Appropriate Regimen for Treating MRSA Ventilator-Associated Pneumonia with Vancomycin?
Clin Pharmacokinet. 2008
Pea F, Viale P.
Department of Experimental and Clinical Pathology and Medicine, Institute of Clinical Pharmacology and Toxicology, Medical School, University of Udine, Udine, Italy.
Meticillin-resistant (methicillin-resistant) Staphylococcus aureus causes unacceptably high mortality from ventilator-associated pneumonia, even when appropriate early therapy with vancomycin is administered at a dosage of 15 mg/kg every 12 hours. However, because of the poor penetration of vancomycin in epithelial lining fluid, it is unlikely that this dosing schedule always achieves optimal vancomycin exposure in the lung. Conversely, there is probably enough evidence to suggest that continuous infusion enhances vancomycin efficacy with the standard 30 mg/kg daily dosage, thus avoiding the need to use higher daily dosages that could increase the risk of nephrotoxicity. It is worth noting that in the case of fully susceptible pathogens with a minimum inhibitory concentration (MIC) of /=360, so that both pharmacodynamic efficacy targets may be optimized.
PMID: 18307369 [PubMed - in process]
Clin Pharmacokinet. 2008
Pea F, Viale P.
Department of Experimental and Clinical Pathology and Medicine, Institute of Clinical Pharmacology and Toxicology, Medical School, University of Udine, Udine, Italy.
Meticillin-resistant (methicillin-resistant) Staphylococcus aureus causes unacceptably high mortality from ventilator-associated pneumonia, even when appropriate early therapy with vancomycin is administered at a dosage of 15 mg/kg every 12 hours. However, because of the poor penetration of vancomycin in epithelial lining fluid, it is unlikely that this dosing schedule always achieves optimal vancomycin exposure in the lung. Conversely, there is probably enough evidence to suggest that continuous infusion enhances vancomycin efficacy with the standard 30 mg/kg daily dosage, thus avoiding the need to use higher daily dosages that could increase the risk of nephrotoxicity. It is worth noting that in the case of fully susceptible pathogens with a minimum inhibitory concentration (MIC) of /=360, so that both pharmacodynamic efficacy targets may be optimized.
PMID: 18307369 [PubMed - in process]
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