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Cystic Fibrosis
resistance determinants other than mecA. SCCmec type IV has been Until now the difficulty in attributing a proper pathogenic role to MRSA
found in most CA-MRSA isolates, which explains why CA-MRSA isolates in CF patients was due to multiple factors. Many patients present with
are most often resistant only to β-lactam antibiotics. pulmonary infections due to polymicrobial flora, so it is problematic to
attribute an exact pathogenic role to a single pathogen isolated in the
CA-MRSA strains differ in a number of important ways from the six airways. Many studies on MRSA published to date are cross-sectional
major pandemic clones of MRSA that account for nearly 70% of or brief and conducted on limited numbers of patients.
12,14,39,42–44
Miall et
epidemic HA-MRSA strains.
31
It has been reported that CA-MRSA strains al., studying a limited number of children infected with MRSA, found
from different parts of the world have different genetic backgrounds, a deterioration in height, weight and body mass index in the MRSA
and different CA-MRSA types are confined to particular geographical group.
12
Compared with the control group, these patients also
areas, representing successful lineages in terms of ability to cause required a greater use of antibiotics.
infection, to persist and to spread, even across continents.
32
Of the
CA-MRSA strains studied thus far, the majority harbour SCCmec type IV, Ren et al., in a study on a large number of patients, observed that
suggesting that this is the most transmissible and best adapted type. The those harbouring MRSA were more frequently hospitalised,
CA-MRSA strains are generally characterised by the production of PVL. necessitating a higher use of antibiotics, and had lower FEV
1
values
The genes encoding for PVL and several other superantigens, such as compared with a control group who had methicillin-susceptible
enterotoxins B and C, have been found in CA-MRSA strains, although the S. aureus (MSSA).
42
Also in this case, the cross-sectional characteristics
pathogenic potential of such strains is not well understood.
33
of the study do not permit us to assign an absolute causal role
between the presence of MRSA in the airways and pulmonary
The presence of PVL genes may often be associated with CA-MRSA, function. Because some of the pathogenic roles of MRSA on
but, to date, this has little predictive value for identifying CA-MRSA.
7,21
pulmonary function in CF patients could be attributable to virulence
PVL is not present in Australian isolates,
34
in Italian MRSA isolates factors produced by the germ itself, Elizur et al. recently speculated on
belonging to SCCmec type IV
13
and in the USA500, a CA-MRSA American the role of the PVL virulence factor.
14
In one study conducted on a
epidemic clone.
23
Although the epidemiology of MRSA in the US seems limited number of patients, those with newly acquired PVL-positive
to be tied to a few epidemic clones, such as USA500 and USA300,
35
in MRSA required more frequent hospitalisation for pulmonary
Europe there are lines frequently associated with epidemic episodes, exacerbations. They presented with a higher number of pulmonary
such as the Iberic clone, and the situation seems more heterogeneous infiltrates as seen by chest X-ray and had more rapid FEV
1
decline
than that in the US.
36
compared with those harbouring PVL-negative MRSA.
45
The proper approach to the study of the global epidemiology of MRSA Another clinical study recently published on 1,732 North American
is MLST analysis. This is a nucleotide sequence-based approach for patients with persistent MRSA infection in follow-up for 3.5 years
the unambiguous characterisation of bacterial isolates. Based on the indicated a more rapid FEV
1
decline (average decline 2.06%
nucleotide sequences of seven different housekeeping genes, it is predicted/year) in patients eight to 21 years of age compared with
possible to assign a sequence type (ST). Isolates are defined by the those patients not harbouring MRSA (average decline 1.44%
alleles present at the seven loci (the allelic profile), and each unique predicted/year).
11
The effect of MRSA on the FEV
1
decline was not
allelic profile is assigned an ST. Isolates with the same ST therefore have clinically significant in adults. The reasons for this observation are
identical sequences at all seven MLST loci and are considered to be not totally clear, but may be due to progressive structural damage to
members of a single clone.
37
The MLST allows global epidemiological the lungs caused by inflammation and chronic infection and the low
analysis, obtaining information about worldwide strain diffusion. sensitivity of FEV
1
as a marker of lung pathology in adults. The
Dasembrook et al. study, although carried out in a large number of
Clinical Role of Methicillin-resistant patients, does not provide indications about the molecular
Staphylococcos aureus in Cystic Fibrosis characteristics of MRSA or the role of PVL virulence factor, and does not
The natural history of MRSA infection in CF patients is only partly differentiate between the roles of CA-MRSA and HA-MRSA.
11
Altogether,
understood.
10,24
Complete information on the persistence of this germ in these data present a peculiar picture of MRSA infection in CF patients.
the airways and its effect on pulmonary function is still lacking. Studies The potential negative effect of MRSA on pulmonary function in CF has
conducted on significant numbers of patients have shown that about been demonstrated in ample numbers of patients, but further studies
30% experience transitory colonisation.
11,38
are needed to verify possible diverse pathogenic effects of MRSA on
the lung in relation to different molecular characteristics of MRSA
At the moment there are no uniformly accepted definitions for the strains. Currently, infection or colonisation with MRSA is not considered
concept of chronic MRSA infection. Recently, persistent MRSA an absolute contraindication for organ transplantation.
46
was defined as three or more MRSA cultures during a follow-up of
3.5 years.
11
Medical Therapy
Obviously, it is best if CF patients do not contract MRSA infection,
The clinical impact of MRSA in CF patients is the subject of a long because it reduces their antibiotic therapy options and possibly
debate. In some experiences the presence of MRSA in the airways causes deterioration in their lung function. As for other pathogens,
of CF patients does not seem to be significantly associated with a eradicating MRSA from the airways of patients affected by CF (see
worsening of the patient’s clinical condition, whereas other studies Table 1) can theoretically benefit the patient and reduce the possibility
have shown that the presence of the germ is associated with a of diffusion of this bacteria.
2
more rapid decline in forced expiratory volume in one second
(FEV
1
) and with a higher percentage of hospitalisation and greater A combination therapy of fusidic acid and rifampin for six months has
use of antibiotics.
11,12,39–42
been demonstrated to be efficacious in the eradication of MRSA from
56 EUROPEAN RESPIRATORY DISEASE
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