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Device
- Associated Infections:
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"A Macroproblem
That Starts With Microadherence"
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Medicine has made great strides during the past several
years. Owing to the enhanced medical knowledge and
advanced technology medical devices are responsible
for a large proportion of nosocomial infections1,
particularly in critically ill patients. In this particular
population of patients, 95% of cases of urinary tract
infection are catheter related, 87% of cases of blood
stream infection originate from an indwelling vascular
catheter, and 86% of cases of pneumonia are associated
with mechanical ventilation.1
The pathogenesis of device
- associated infection centers around the multifaceted
interaction among the bacteria, the device and the
host.2
Bacterial factors are probably the most important
in the pathogenesis of infection
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PATHOGENESIS
OF DEVICE RELATED INFECTION
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Device-related infection results from the multifaceted
interaction of bacteria, device, and host factors.
Of these 3 factors, bacterial factors are probably
the most important in the pathogenesis of device-associated
infection, whereas device factors are the most amenable
to modification with the objective of preventing infection.
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BACTERIAL
FACTORS
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Different bacteria use different
adhesins to colonize medical devices. The present
article briefly discussess the adherence properties
of common pathogens, including Staphylococcus aureus
and Staphylococcus epidermidis (the 2 most common
causes of infection of intravascular, orthopedic,
and penile devices), as well as Providencia stuartii
and Escherichia coli, which commonly cause infection
of urological devices and biliary stents.
S. epidermidis
Adherence of S. epidermidis to the surface of the
device is not a one-time phenomenon but rather an
evolving process. Initially, there is a rapid attachment
of bacteria to the surface of the device that is mediated
either by nonspecific factors (such as surface tension,
hydrophobicity, and electrostatic forces) or by specific
adhesins (including the proteinaceous autolysin encoded
by the atIE gene and the capsular polysaccharide intercellular
adhesin [PSA] probably encoded by the ica operon).3
This initial phase of S. epidermidis adherence is
followed by an accumulative phase during which bacteria
adhere to each other and form a biofilm, a process
that is mediated by the polysaccharide intercellular
adhesin (PIA) encoded by the ica operon.4
S.aureus
Unlike S. epidermidis,
which uses well-defined adhesins on the bacterial
surface to adhere to one another and to the device,
adherence of S. aureus appears to be more dependent
on the presence of host-tissue ligands, including
fibronectin, fibrinogen, and collagen. S. aureus adheres
to such host-tissue ligands via genetically defined
microbial surface proteins, commonly referred to as
"microbial surface components recognizing adhesive
matrix molecules".5,6
The most important MSCRAMMs include FnbpA and FnbpB,
which bind to fibronectin; clumping factor, which
binds to fibrinogen; and collagen adhesin, which binds
to collagen.
P. stuartii
In general, much less is known about the adherence
of gram-negative bacilli than gram-positive cocci
to medical devices. P. stuartii is more prevalent
in the urinary tract of patients with long-term bladder
catheters than it is in catheter-free patients. Persistent
adherence of P. stuartii to urinary catheters is thought
to be mediated by type 3 fimbriae on the basis of
the following observations (1) bacterial isolates
that caused long-term (> 12 weeks) bacteriuria
expressed type 3 fimbriae more than did isolates that
caused short-term (< 1 week) bacteriuria (74% vs.
26%, respectively)7
in catheter-dependent patients (2)bacterial isolates
that expressed type 3 fimbriae bound in higher numbers
to catheters than did isolates that did not express
type 3 fimbriae, and (3) bacterial isolates that expressed
type 3 fimbriae bound less to Tomm Harsfall protein
(an inhibitory urinary protein) than did bacterial
isolates that did not express type 3 fimbriae).7
E.coli
Despite the plethora of data on the adherence of E.coli
to the uroepithelium, relatively little is known about
adherence of this organism to urological devices.
E.coli isolates that caused long-term (> 12 weeks)
bacteriuria expressed type 1 fimbriae more than did
isolates that caused short-term (< 1 week) bacteriuria
(92% vs. 59%, respectively).8
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DEVICE FACTORS
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The presence of the devices can in and of itself enhance
bacterial virulence. Careful analysis of the data
on bacterial adherence and surface modification of
the device yields the following 5 major principles:
- Different bacteria may adhere
differently to the same device material;
- The same bacteria may adhere
differently to different device materials;
- The same bacteria may adhere
differently to the same device material placed under
different circumstances, including the medium in which
the device is placed (hydrophobic vs. hydrophilic
medium), type of flow (dynamic vs. stationary), and
temperature
- In vitro inhibition of bacterial
colonization of the device does not ensure anti-infective
efficacy in vivo; and
- The clinical benefit of a
particular surface-modifying approach may vary from
one application to another. Notwithstanding these
5 major principles, there are also a number of device-related
factors that can affect bacterial adherence to the
device, including the source of device material, surface
of the device, and shape of the device (Table 1).
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Table 1: Device related factors that
may favor bacterial adherence
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Type of device
material
Polyvinyl chloride favors
bacterial adherence more than does Teflon
Polyethylene favors bacterial adherence more than
does polyurethane
Latex favors bacterial adherence more than does
silicone
Silicone favors bacterial adherence more than does
polytetrafluoroethylene
Stainless steel favors bacterial adherence more
than does titanium
Source of device material
Synthetic favors bacterial
adherence more than does biomaterial
Surface of device
Irregular favors bacterial
adherence more than does regular
Textured favors bacterial adherence more than does
smooth
Hydrophobic favors bacterial adherence more than
does hydrophilic
Shape of device
Polymeric tubing favors bacterial
adherence more than does wire mesh |
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HOST FACTORS
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These factors can be divided into two groups: (1)
host factors that can affect bacterial adherence of
bacteria to the device, including tissue ligands that
mediate adherence of the MSCRAMM-positive bacteria
to a variety of medical devices; and (2) host factors
that can either promote or inhibit the persistence
of already adherent bacteria on the surface of the
device. Studies 1,9
have indicated that S.aureus binds more to the surfaces
of vascular catheters and E.coli binds more to biliary
stents. The contribution of host-tissue ligands to
bacterial adherence was further supported by the demonstration
that S.aureus binds more to catheters coated with
fibronectin or fibrinogen than to uncoated catheters.
Immune-mediated phenomena
that promote bacterial persistence are illustrated
by the reduced complement-mediated opsonic activity
and the decreased bactericidal activity of WBCs in
tissues surrounding the implanted device.9
The most studied immune mediator that can inhibit
persistence of already adherent bacteria on the surface
of the device is IFN - g
. This immune mediator reduces the intracellular persistence
of S.epidermidis in macrophages around catheters subcutaneously
implanted in mice and inhibits catheter colonization.10
IFN - g
may exert this protective antibacterial effect by
inducing major histocompatibility complex class II
proteins on phagocytic cells, activating mononuclear
phagocytes, and regulating humoral immune response.
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KOCH'S POSTULATES FOR BACTERIAL ADHERENCE/INFECTION
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Koch's postulates were originally conceived almost
two centuries ago for identification of the bacterial
causes of epidemic diseases, modified versions, such
as the "molecular version" of Koch's postulates,
have been constructed and applied for other aspects
of medical diseases.2,11
With the vast increase in knowledge of the
molecular and physiochemical properties of bacterial
adhesins, it is only proper to make an attempt to
construct an "adherence/infection" version
of Koch's postulates (Table 2).
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Table 2: The adherence/infection version
of Koch's postulates
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| Postulate |
Adherence of infection
version |
| 1. |
The
gene(s) responsible for an adhesin is (are) more
prevalent in clinical strains that cause device-associated
infection than in strains that do not cause infection |
| 2. |
Deletion
or inactivation of the gene(s) responsible for an
adhesin results in reduced pathogenicity in animal
models. |
| 3. |
Antibodies
to adhesins protect against device-associated infections
in vivo. |
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CONCLUSION
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The serious medical consequences and soaring economic
sequelae of device-associated infections underscore
the importance of prevention. At the present time,
the most commonly used preventive approach is surface
modification of the device with the objective of inhibiting
bacterial presence in the biofilm hoping to prevent
device-associated infections. The surface of the device
can be modified either with or without the use of
antimicrobial agents. The antimicrobial-use approach
for surface modification has had variable clinical
success, with differences in the degree of protection
attributed to the location of the device, concentration,
type of infecting pathogens, type of antimicrobial
agents used for coating the device, concentration
of antimicrobial agents on the surface of the coated
device, and degree of leaching of the antimicrobial
agent off the coated surface to produce a zone of
inhibition
Recent preliminary data12
also suggested that naturally existing substances,
such as furanones, can prevent formation of biofilm
around oil pipes placed in deep water. Although such
an outcome may be ideal, it is still too early to
predict whether this approach can be applied safely
and effectively in clinical medicine.
Because biofilm is so ubiquitous
in nature, it may not be feasible to eliminate it.
Instead, it is probably more feasible to use the approach
of bacterial interference to replace biofilms that
are a result of pathogenic bacteria with biofilms
that are a result of less pathogenic or nonpathogenic
bacteria. In other words, bacterial adherence may
be used to circumvent rather than enhance clinical
infection. Earlier in vitro studies indicated that
coating of polymers with Lactobacillus acidophilus
decreases the adherence of S. epidermidis and E.coli
to the modified surfaces.13 A recent report indicated
that bladder catheters coated with a nonpathogenic
strain of E.coli 83972 reduce the adherence of Enterococcus
faecalis to the catheter in vitro. The clinical efficacy
of inserting bladder catheters coated with this nonpathogenic
organism has yet to be examined. Because the introduction
of nonpathogenic bacterial strains into the human
body has a potential, although unlikely, risk of causing
symptomatic infection, the clinical safety of this
approach of bacterial interference is currently being
examined.
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TO SUMMARIZE
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Traditional surface-modifying preventing approaches
have largely focused on antimicrobial coating of devices
and resulted in variable clinical success in preventing
device assoiated infections. The potential protective
role of newer innovative approaches: such as biofilm
modification and bacterial interference, ought to
be further investigated.|
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REFERENCES
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1. Crit
Care Med 1999; 27: 887-92
2. CID 2001: 33 (1 Nov): 1567-72
3. Infect Immun 1999; 67: 2627-32
4. J. Infect Dis 2000; 182: 351-5
5. J Med Microbiol 1997; 46: 75-9
6. Mol Microbiol 1995; 17: 1143-5
7. J Infect Dis 1988; 157: 264-71
8. J. Clin Microbiol 1987; 25: 2253-7
9. J Infect Dis 1982; 146: 487-97
10. J Infect Dis 2000; 181: 1337-49
11. 1st ed. Washington:ASM Press; 1994:30-46
12. Science 1998; 280: 295-8
13. J Biomed Mater Res 1990; 24: 39-46
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