INFECTION HOT TOPIC

10.1111/j.1469-0691.2011.03748.x

Burden of Staphylococcus aureus endocarditis: how real is the threat?

E. Tacconelli
Department of Infectious Diseases, Universita` Cattolica, Rome, Italy
E-mail: etacconelli@rm.unicatt.it

Article published online: 1 December 2011

Staphylococcus aureus represents an interesting example of how

strong the relationship between healthcare professionals and
government policies can become after wide media involvement
[1]. A Google News search for S. aureus for the last 3 years
retrieved more than 4000 articles in non-scientific journals
focused on the threat of the superbug among hospitalized
patients and the community. In 2009, an interesting paper by
Boyce showed that the UK press exhibited a high interest in
methicillin-resistant S. aureus (MRSA) as compared with that of
the USA [2]. Healthcare workers, experts and professional
bodies have strongly criticized the nature of media reporting,
but have had little influence on or involvement in the press.
However, the strong engagement of civil society and politicians
led to attention and funds being devoted to this issue, which
was only partly covered before the media interest. Therefore,
it was not unexpected when the sharp increase in the rate of
hospitalizations for bacterial infective endocarditis in the USA,
mainly driven by S. aureus, recently reported at the Interscience Conference on Antimicrobials and Chemotherapy in
Chicago, again attracted attention of the public and media
interest (Federspiel et al., 51st ICACC, 2011, L1-387).
The authors analysed, through a retrospective cohort
study, the trends and characteristics of 83 700 hospitalizations for bacterial endocarditis during a 10-year period in
the USA. The trends showed an increase in the overall rate
of hospitalizations for bacterial endocarditis over time, from
11.4 to 16.6 discharges/100 000 population-years between
1999 and 2008. The annual rate increased by 46%, although
most of the increase occurred before 2006. Among admissions where an organism was identified, the majority (71%)
of the growth in incidence was attributable to S. aureus.
Overall, S. aureus was the most common organism identified
(46%), followed by streptococci/enterococci (33%) and coagulase-negative staphyloccoci (8%). After adjustment for
demographics and comorbidities, S. aureus-related endocarditis was associated with significantly higher in-hospital
mortality (risk difference: +5.9%) and inpatient charges (difference: +$19 280) and longer hospitalizations (difference:
+2.26 days) than streptococcal/enterococcal endocarditis
(Federspiel et al., 51st ICACC, 2011, L1-387).

However, before generalizing results and deriving solutions for European hospitalizations, some threats to the
validity of the study should be underlined. First, the
researchers were able to determine the causative pathogen
for 56% of the hospitalizations only, and, although the number of unidentified cases was roughly parallel with the number of total cases, this might have introduced a reporting
bias. Second, and more important from an infection control
point of view, distinction between cases caused by MRSA
and methicillin-susceptible S. aureus (MSSA) and definition of
the site of acquisition (community vs. hospital vs. healthcare
facilities) were not possible. The lack of this information prevents public health officers, epidemiologists and infection
control practitioners from analysing the origin of clones and
suggesting future steps for prevention.
However, some hypotheses might be outlined. First, if the
increase has arisen from community-acquired cases, then
possible changes in the outpatient population need to be
ascertained. The rise might be attributed to the increase in
the number of cases caused by intravenous drug usage or, as
I suspect, to the change in the number of immunocompromised patients, mainly in relation to the wide usage of biological agents, as anti-tumour necrosis factor therapies [3].
Another reason for the increase can be derived from the
observation reported by Furuno and coworkers on the US
human immunodeficiency virus population. The authors
observed that community-acquired MRSA was significantly
associated with an increased incidence of endocarditis in a
cohort of human immunodeficiency virus patients with MRSA
bacteraemia [4]. A better understanding of the population in
which the increase in endocarditis was observed would allow
the development of infection control measures and prevention therapies that differ according to patients comorbidities
and type of immunosuppression. We should also take into
consideration that the rise in S. aureus endocarditis could be
a consequence of the circulation of different strains [5]. For
example, in the reduction of the MRSA epidemic that was
observed in the UK, the marked decline was associated, in
particular, with one of the clones that previously dominated
the epidemic (sequence type (ST)36) [6,7]. On the other

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Clinical Microbiology and Infection, Volume 18 Number 2, February 2012

hand, the expansion and decline of MSSA clones and rate

have been less extensively studied at the European level.
Second, if the rise in endocarditis was attributable to hospital-acquired MRSA cases, an increase in the frequency of
cardiothoracic surgery and/or the use of bone and joint
prostheses might have been the cause, and should be investigated [8,9]. In opposition to this hypothesis, recent data
show that, in many European countries, a decrease in MRSA
bacteraemia in recent years has been reported. On the basis
on data collected by the European Antimicrobial Resistance
Surveillance Network (EARS-Net) and the former EARSS,
from 198 laboratories in 22 European countries up to 2009
[10], the number of bloodstream infections caused by S. aureus increased by 34%. However, the proportion of methicillin-resistant isolates decreased. An interesting recent
prospective study, performed at the University of Chicago,
compared the genotypes of MRSA and MSSA infecting bacterial strains observed from 2001 to 2005 [11]. MSSA
patients were more likely to suffer from bacteraemia, endocarditis or sepsis and to be in the intensive-care unit at the
time of culture. MRSA and MSSA patients did not significantly differ in the proportion of hospital-acquired cases.
The genetic backgrounds of MRSA and MSSA multilocus
ST1, ST5, ST8, ST30 and ST59 covered, in combination,
94% of MRSA isolates and 51% of MSSA isolates. The
authors suggested that a possible role reversal has occurred
for MSSA and MRSA strains in hospitals [11]. These observations further underline the importance of genotypic analysis of relevant clones responsible for severe infections
caused by S. aureus, regardless of the methicillin susceptibility. Therefore, surveillance data should be integrated with
typing results to provide rapid identification of relevant
clones at the national and international levels, and therefore
determination of which environmental factors contributed
to their spread [5].
However, we should not underestimate the relevance of
the US cohort study in particular if the increase in S. aureus
endocarditis is related to the increase in the frequency of
MSSA. A recent paper from de Kraker on behalf of the BURDEN project (Burden of Resistance and Disease in European
Nations) analysed the trends of and expected mortality
caused by S. aureus bacteraemia from 1293 hospitals in 31
European countries [12]. The headline results were an estimated 27 711 MRSA cases and 80 723 MSSA cases; the
excess mortality was 5503 for MRSA and 7261 for MSSA,
with the UK and France experiencing the highest burden of
S. aureus-related deaths. Although the study predicted that,
in 2015, Escherichia coli resistant to third-generation cephalosporins will surpass MRSA in causing severe infections, the
burden of the disease associated with S. aureus and, in partic-

CMI

ular, with MSSA will be so important that its underestimation

will not be acceptable.
Currently, the difficult financial situation of the European
Union, caused by the global economic crisis, will significantly
impact on healthcare decisions and the destination of funds.
Given the recent data on the burden of endocarditis and
bacteraemia, it would be very difficult not to agree that
severe infections caused by S. aureus are among the priorities. Therefore, we need accurate definitions of the epidemiology and microbiology of S. aureus circulation, including
genotyping data on the diffusion of clones. Efforts should be
undertaken to enlarge surveillance networks in all European
countries. Only with the availability of all information will
public health officers and politicians with major interests in
healthcare develop international programmes for the reduction of the burden of severe infections caused by S. aureus at
the community and hospital levels.

Transparency Declaration
None.

References
1. Tacconelli E. The management of methicillin-resistant Staphylococcus
aureus infection in Europe. Clin Microbiol Infect 2010; 16 (suppl 1): 1
2.
2. Boyce T, Murray E, Holmes A. What are the drivers of the UK
media coverage of meticillin-resistant Staphylococcus aureus, the interrelationships and relative influences? J Hosp Infect 2009; 73: 400407.
3. Winthrop KL, Chiller T. Preventing and treating biologic-associated
opportunistic infections. Nat Rev Rheumatol 2009; 5: 405410.
4. Furuno JP, Johnson JK, Schweizer ML et al. Community-associated
methicillin-resistant Staphylococcus aureus bacteremia and endocarditis
among HIV patients: a cohort study. BMC Infect Dis 2011; 11: 298304.
5. Wyllie D, Paul J, Crook D. Waves of trouble: MRSA strain dynamics
and assessment of the impact of infection control. J Antimicrob Chemother 2011; 66: 26852688.
6. Wyllie DH, Walker AS, Miller R et al. Decline of meticillin-resistant
Staphylococcus aureus in Oxfordshire hospitals is strain-specific and preceded infection-control intensification. BMJ Open 2011; 1: e000160.
7. Ellington MJ, Hope R, Livermore DM et al. Decline of EMRSA-16
amongst methicillin-resistant Staphylococcus aureus causing bacteraemias in the UK between 2001 and 2007. J Antimicrob Chemother 2010;
65: 446448.
8. Anderson DJ, Arduino JM, Reed SD et al. Variation in the type and
frequency of postoperative invasive Staphylococcus aureus infections
according to type of surgical procedure. Infect Control Hosp Epidemiol
2010; 31: 701709.
9. Cataldo MA, Petrosillo N, Cipriani M, Cauda R, Tacconelli E. Prosthetic joint infection: recent developments in diagnosis and management. J Infect 2010; 61: 443448.
10. Gagliotti C, Balode A, Baquero F et al. EARS-Net Participants (Disease Specific Contact Points for AMR). Escherichia coli and Staphylococcus aureus: bad news and good news from the European

2011 The Authors

Clinical Microbiology and Infection 2011 European Society of Clinical Microbiology and Infectious Diseases, CMI, 18, 107109

Infection Hot Topic

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Antimicrobial Resistance Surveillance Network (EARS-Net, formerly

EARSS), 2002 to 2009. Euro Surveill 2011; 17: 1620.
11. David MZ, Boyle-Vavra S, Zychowski DL, Daum RS. Methicillin-susceptible Staphylococcus aureus as a predominantly healthcare-associated
pathogen: a possible reversal of roles? PLoS ONE 2011; 6: e18217.

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12. De Kraker ME, Davey PG, Grundmann H, on behalf of the BURDEN

study group. Mortality and hospital stay associated with resistant
Staphylococcus aureus and Escherichia coli bacteremia: estimating the
burden of antibiotic resistance in Europe. PLoS Med 2011;8:
e1001104.

2011 The Authors

Clinical Microbiology and Infection 2011 European Society of Clinical Microbiology and Infectious Diseases, CMI, 18, 107109