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Methicillin-resistant Staphylococcus aureus in Cystic Fibrosis
whereas most community-associated strains are susceptible to Fibrosis Foundation Patient Registry indicating that in 2001 MRSA could
tetracyclines, trimethoprim–sulfamethoxazole and clindamycin.
6,8,16,17
be cultured from respiratory tract secretions from 7% of CF patients. In
2006, this increased to 18.9%.
3,10,11
It is not clear whether this increase in
Epidemiology MRSA prevalence in CF patients is due to HA-MRSA or CA-MRSA strains.
MRSA is now recognised as a public health problem worldwide Because CF patients undergo frequent hospitalisation they have
because of increasing rates of infection in many settings.
5,6,18
Studies normally been assumed to be at risk of acquiring HA-MRSA, but recent
analysing risk factors for acquiring MRSA in patients not affected by CF molecular studies have shown instead a prevalence of CA-MRSA as a
show that the risks of nasal carriage of healthcare-associated MRSA causative organism.
26–28
Glikman et al. observed that the majority of
(HA-MRSA) include hospitalisation, prolonged hospital stay, frequent
contact with a healthcare environment, recent (within the previous 60
days) antimicrobial use or frequent contact with an individual with one
The molecular basis on which
or more of the preceding risk factors.
6,19
In non-CF environments,
infections caused by MRSA occur primarily in healthcare environments,
CA-MRSA and HA-MRSA are distinguished
although recently there has been an increase in MRSA epidemics in
is the difference in the mobile genetic
rural and urban areas that do not have any contact with healthcare
environments. These observations suggest that the epidemiology of
element SCCmec integrated into the
MRSA infections is changing.
10,16
MRSA chromosome.
From a microbiological point of view, the community-associated MRSA
(CA-MRSA) strains differ from HA-MRSA strains in that they are usually MRSA strains isolated from CF patients are HA-MRSA, but during their
susceptible to clindamycin and other non-β-lactam antibiotics. However, study they found a high percentage (26%) of isolated CA-MRSA,
the level of their resistance is increasing and geographically variable.
20
suggesting that CA-MRSA may become predominant in CF patients,
On a genetic level, the type IV or V variants of the gene cassette codify especially in those who are newly colonised.
26
Among Belgian patients in
for methicillin resistance (SCCmec). Furthermore, CA-MRSA strains nine CF centres, HA-MRSA strains were found in 55% of isolates,
ususally carry the two genes encoding for the pore-forming toxin named whereas 45% carried SCCmec IV, the genetic marker usually associated
Panton-Valentine leukocidin (PVL). In non-CF environments, CA-MRSA with CA-MRSA strains.
26
In the experience of Elizur et al., most of the
strains synthesise PVL (PVL+); are responsible for tissue necrosis; are MRSA isolates had the characteristics of HA-MRSA with SCCmec II, but
cytolytic to macrophages, monocytes and polymorphonuclear 25% had SCCmec IV, suggesting an important role of CA-MRSA in this
granulocytes; and have been linked epidemiologically to cutaneous and case.
14
In spite of the high risk of HA-MRSA acquisition due to frequent
more severe infections.
21,22
Recent studies have demonstrated that the hospitalisations, a high prevalence of CA-MRSA (31.4%) was
CDC definition underestimates the CA-MRSA prevalence because many demonstrated in CF patients in Italy.
28
Preliminary results emerging from
patients previously exposed to the healthcare environment harbour studies published up until now suggest that CA-MRSA strains are now
strains of the multilocus sequence type (MLST)
8
typical of CA-MRSA, with spreading to the CF population.
13,28
clindamycin susceptibility, SCCmec IV-bearing and PVL+.
7,23
Microbiology
In the US, CA-MRSA strains are described as being in continuous The isolation and identification of MRSA is based on the use of specific
increase in nosocomial environments, with a tendency to progressively culture media and tests available to all diagnostic microbiology
replace strains considered to be responsible for hospital infections (HA- laboratories. The correct differentiation between CA-MRSA and HA-
MRSA). In Europe, the prevalence of infections attributable to CA-MRSA MRSA necessitates a specific molecular genetic approach that is
seems to be lower than in the US, but is continuously increasing.
4,24
available only in specialised laboratories. The molecular basis on which
Recent observations based on molecular studies suggest that the CA-MRSA and HA-MRSA are distinguished is the difference in the mobile
association with a healthcare environment has little predictive value for genetic element SCCmec integrated into the MRSA chromosome. The
distinguishing patients infected by CA-MRSA from those with HA-MRSA.
7
resistance to penicillin and β-lactams is due to the production of altered
penicillin-binding proteins (PBPs) with reduced affinity for methicillin and
The data regarding the epidemiology of MRSA in CF patients should be less toxic β-lactams. This genetic element carries the gene responsible
considered to be partial, and only a small number of studies have for resistance to methicillin, the mecA gene, which encodes for a
analysed this issue.
10,12,14,24–28
The prevalence of MRSA varies from CF penicillin-binding protein (PBP-2) responsible for a decreased binding
centre to centre. Miall et al. reported that the prevalence of MRSA affinity for β-lactam antibiotics. SCCmec elements have two essential
increased from no patients in 1992 to seven patients in 1998, for components: the ccr gene complex (ccr) and the mec gene complex
example.
12
Campana et al. reported that MRSA was present in sputum (mec). Several mec and ccr allotypes have been found among SCCmec
samples in 6.7% of patients attending an Italian CF centre.
25
Patients elements, which has led to the classification of SCCmec types I, II, III, IV
were also infected by genotypically different strains.
25
Elizur et al. and V.
29
HA-MRSA strains belong to SCCmec types I, II and III, and
reported from a single centre that the prevalence of MRSA had SCCmec types IV and V to Ca-MRSA. In SCCmec type I no antibiotic
increased from 22 to 27% in three years.
14
Preliminary data from an resistance determinants, except for those carried by mecA (β-lactams),
Italian cross-sectional study indicate that 181 (7.6%) of 2,362 CF patients are found. By contrast, types II and III contain multiple determinants for
from nine centres were colonised with MRSA.
24,28
non-β-lactam antibiotic resistance and provide a molecular explanation
for the multiple drug resistance often documented in MRSA isolates
Even if the increase in prevalence of MRSA seems less relevant in CF circulating in healthcare environments. The large size of SCCmec types I
patients as opposed to other patient populations, there has been a and II probably limits their horizontal transfer.
30
The SCCmec types IV and
notable increase in incidence, as witnessed by data from the Cystic V are smaller in size than types I–III and, like SCCmec type I, lack
EUROPEAN RESPIRATORY DISEASE 55
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