<div align="center"><a name="Infec-Moss"><b>Bacterial Resistance
and Infection Control</b></a><br>
by Richard Moss, M.D.</div>
<blockquote><span style=" font-size: x-small;">Many patients and
families are concerned about infection control and the measures
taken at our CF Center to reduce the risk of transmission of
resistant bacteria while continuing to foster a sense of community
and support. Here are some relevant facts which may help explain
our policies and procedures.
<span style=" font-size: x-small;">First, it is essential to
understand what we mean when we talk about resistance of bacteria
to antibiotics. What does it really mean?
<span style=" font-size: x-small;">There are 4 categories of
bacterial sensitivity to antibiotics:
<ul>
<li><span style=" font-size: x-small;">First, pansensitive - this
means the bug is sensitive to all the antibiotics usually tested
for potential treatment.</li>
<li><span style=" font-size: x-small;">Second, sensitive - the bug
is sensitive to several potential antibiotics, but it may be
resistant to others.</li>
<li><span style=" font-size: x-small;">Third, multiresistant - this
is more complicated. According to the current definition, this
means the bug is resistant to all antibiotics in two or more
classes of antibiotics. Currently 3 classes of antibiotics are
considered appropriate for treatment of Pseudomonas: certain
beta-lactams, such as ceftazidime (Fortaz®); certain quinolones,
such as ciprofloxacin (Cipro®); and aminoglycosides, such as
tobramycin (Nebcin®, Tobi®).</li>
<li><span style=" font-size: x-small;">Fourth, panresistant - the
bug is resistant to all tested antibiotics of all
classes.</li>
</ul>
<h3><span style=" font-size: x-small;">CASE STUDY</h3>
<span style=" font-size: x-small;">Here is an example of an
antibiotic sensitivity report for fictional patient Jane Smith on a
clinic visit expectorated sputum culture that grew three strains of
Pseudomonas aeruginosa, one strain of Stenotrophomonas maltophilia,
and Staphylococcus aureus. What is listed is the antibiotic
sensitivity pattern for 1 of the 3 strains of Pseudomonas, i.e.,
just one of 5 lists of antibiotic sensitivities we would get from
this single culture report on this patient on this day:
<table>
<tr>
<th><span style=" font-size: x-small;">"3+ mucoid Pseudomonas
aeruginosa</th>
</tr>
<tr>
<td><span style=" font-size: x-small;">Method</td>
<td><span style=" font-size: x-small;">Kirby Bauer</td>
</tr>
<tr>
<td><span style=" font-size: x-small;">Ticarcillin</td>
<td><span style=" font-size: x-small;">Resistant</td>
</tr>
<tr>
<td><span style=" font-size: x-small;">Piperacillin</td>
<td><span style=" font-size: x-small;">Resistant</td>
</tr>
<tr>
<td><span style=" font-size: x-small;">Ceftazidime</td>
<td><span style=" font-size: x-small;">Intermediate</td>
</tr>
<tr>
<td><span style=" font-size: x-small;">Ciprofloxacin</td>
<td><span style=" font-size: x-small;">Resistant</td>
</tr>
<tr>
<td><span style=" font-size: x-small;">Imipenem</td>
<td><span style=" font-size: x-small;">Resistant</td>
</tr>
<tr>
<td><span style=" font-size: x-small;">Gentamicin</td>
<td><span style=" font-size: x-small;">Resistant</td>
</tr>
<tr>
<td><span style=" font-size: x-small;">Tobramycin</td>
<td><span style=" font-size: x-small;">Resistant</td>
</tr>
<tr>
<td><span style=" font-size: x-small;">Amikacin</td>
<td><span style=" font-size: x-small;">Resistant</td>
</tr>
<tr>
<td><span style=" font-size: x-small;">Aztreonam</td>
<td><span style=" font-size: x-small;">Intermediate</td>
</tr>
<tr>
<td><span style=" font-size: x-small;">Cefepime</td>
<td><span style=" font-size: x-small;">Sensitive</td>
</tr>
<tr>
<td><span style=" font-size: x-small;">Meropenem</td>
<td><span style=" font-size: x-small;">Resistant</td>
</tr>
</TBODY></table>
<table>
<tr>
<th><span style=" font-size: x-small;">Tobramycin E test (not yet
FDA approved)</th>
</tr>
<tr>
<td><span style=" font-size: x-small;">MIC 32</td>
<td><span style=" font-size: x-small;">No
interpretation"</td>
</tr>
</TBODY></table>
<span style=" font-size: x-small;">What is your categorization
of this bug, and how should Jane Smith be approached regarding
infection control on a clinic visit? You wouldn't be expected to
know the answer without a lot more knowledge of how the tests are
done and what they mean. Here are several points about this culture
result:
<ul>
<li><span style=" font-size: x-small;">This bug is multiresistant.
This is because it is resistant to all tested antibiotics in 2 out
of the three 3 represented.
<ol>
<li><span style=" font-size: x-small;">The only quinolone tested
(because it has the highest and only frequently present quinolone
activity against Pseudomonas) is ciprofloxacin.
Resistant.</li>
<li><span style=" font-size: x-small;">The three aminoglycosides
tested are gentamicin, tobramycin, and amikacin. Resistant to all
three.</li>
<li><span style=" font-size: x-small;">The rest of the drugs
shown--total of 7--are beta-lactams. Of these 7 drugs, the bug is
sensitive to just one, cefepime. This sensitivity keeps the bug
from being called panresistant. But because it is multiresistant
Jane will be asked to don a mask for her clinic visit, and if
hospitalized she will have respiratory isolation procedures in
place.</li>
</ol>
</li>
<li><span style=" font-size: x-small;">Because it is multiresistant
does it mean Jane is untreatable? No! If she is sick we can start
cefepime (an iv-only drug). We would probably combine that with iv
tobramycin, because even though the report says she is resistant to
tobramycin there is synergy between these two antibiotic classes in
attacking Pseudomonas.</li>
<li><span style=" font-size: x-small;">If Jane is a little sick, or
her PFTs have dropped, we may put her on Tobi®. Why? Although the
conventional test (Kirby Bauer disc diffusion) says her bug is
resistant to tobramycin, the "E test" done at Stanford
(not commonly done elsewhere) shows the bug can be killed by
tobramycin if a concentration of 32 micrograms per milliliter
[mcg/ml] can be achieved. It is difficult to do this by iv
tobramycin without risking toxicity to kidneys or inner ear, but it
is easy to do by having Jane inhale 300 milligrams of tobramcyin
solution for inhalation-a Tobi® dose -- twice daily. This will
produce a sputum level in the neighborhood of 1,000 mcg/ml, far
above that needed to kill the bug, even after allowing for the fact
that tobramycin can lose up to 90% of its activity in CF
sputum.</li>
</ul>
<h3><span style=" font-size: x-small;">THE CONCEPT OF RESISTANCE -
A RED HERRING IN CF?</h3>
<span style=" font-size: x-small;">We have problems even defining
and understanding what resistance means in the world of CF. The
word resistance refers to lab tests done in a liquid suspension
with a conventional set "dose" of bacteria and cutoffs
between "sensitive" and "resistant" refer to
levels of that antibiotic traditionally associated with curing
systemic (i.e, blood) infections.
<span style=" font-size: x-small;">We know in CF that the
conventional term "resistance" is questionable
clinically. For example, if your Pseudomonas is called
"resistant" because tobramycin does not kill it at the
conventional testing cutoff level of 8 mcg/ml, this is not very
relevant in a disease where the bug is living in the mucus rather
than tissue or blood, and we can deliver 1,000 mcg/ml Tobi® to the
mucus by aerosol. Moreover, the way the bug lives in your lung is
as a mucoid biofilm-a gigantic communal mass of bacteria (up to one
billion bacteria in one gram of sputum!) stuck together by a slimy
material called alginate or mucoid exopolysaccharide. This is much
different than the way lab antibiotic testing is done with
individual bugs swimming around freely in liquid
suspension.
<h3><span style=" font-size: x-small;">INFECTION
CONTROL</h3>
<span style=" font-size: x-small;">We rely on universal direct and
indirect contact precautions for ALL patients to reduce
transmission of bacteria. The simplest way to describe this is to
imagine a three foot zone around your body that should ideally not
be entered by another patient (unless you live with them), and no
shared object use without proper cleaning in between. All contacts
by caregivers should be preceded by handwashing and cleaning of
multi-use instruments such as stethoscopes.
<span style=" font-size: x-small;">We are concerned about
acquisition and spread of Pseudomonas, and the infection control
measures are designed to reduce the chance of spread. For
multiresistant and panresistant bugs, we add restrictions on the
patient such as use of mask when coming to clinic, and isolation
when hospitalized. This is done to reduce the chance of
transmission, not because the patient is sicker! The mask is an
additional level of precaution but contact precautions are the key
element for ALL patients.
<span style=" font-size: x-small;">In the near future the CFF
Consensus Conference report on Infection Control will be published
and available for detailed reading.
</blockquote>
and Infection Control</b></a><br>
by Richard Moss, M.D.</div>
<blockquote><span style=" font-size: x-small;">Many patients and
families are concerned about infection control and the measures
taken at our CF Center to reduce the risk of transmission of
resistant bacteria while continuing to foster a sense of community
and support. Here are some relevant facts which may help explain
our policies and procedures.
<span style=" font-size: x-small;">First, it is essential to
understand what we mean when we talk about resistance of bacteria
to antibiotics. What does it really mean?
<span style=" font-size: x-small;">There are 4 categories of
bacterial sensitivity to antibiotics:
<ul>
<li><span style=" font-size: x-small;">First, pansensitive - this
means the bug is sensitive to all the antibiotics usually tested
for potential treatment.</li>
<li><span style=" font-size: x-small;">Second, sensitive - the bug
is sensitive to several potential antibiotics, but it may be
resistant to others.</li>
<li><span style=" font-size: x-small;">Third, multiresistant - this
is more complicated. According to the current definition, this
means the bug is resistant to all antibiotics in two or more
classes of antibiotics. Currently 3 classes of antibiotics are
considered appropriate for treatment of Pseudomonas: certain
beta-lactams, such as ceftazidime (Fortaz®); certain quinolones,
such as ciprofloxacin (Cipro®); and aminoglycosides, such as
tobramycin (Nebcin®, Tobi®).</li>
<li><span style=" font-size: x-small;">Fourth, panresistant - the
bug is resistant to all tested antibiotics of all
classes.</li>
</ul>
<h3><span style=" font-size: x-small;">CASE STUDY</h3>
<span style=" font-size: x-small;">Here is an example of an
antibiotic sensitivity report for fictional patient Jane Smith on a
clinic visit expectorated sputum culture that grew three strains of
Pseudomonas aeruginosa, one strain of Stenotrophomonas maltophilia,
and Staphylococcus aureus. What is listed is the antibiotic
sensitivity pattern for 1 of the 3 strains of Pseudomonas, i.e.,
just one of 5 lists of antibiotic sensitivities we would get from
this single culture report on this patient on this day:
<table>
<tr>
<th><span style=" font-size: x-small;">"3+ mucoid Pseudomonas
aeruginosa</th>
</tr>
<tr>
<td><span style=" font-size: x-small;">Method</td>
<td><span style=" font-size: x-small;">Kirby Bauer</td>
</tr>
<tr>
<td><span style=" font-size: x-small;">Ticarcillin</td>
<td><span style=" font-size: x-small;">Resistant</td>
</tr>
<tr>
<td><span style=" font-size: x-small;">Piperacillin</td>
<td><span style=" font-size: x-small;">Resistant</td>
</tr>
<tr>
<td><span style=" font-size: x-small;">Ceftazidime</td>
<td><span style=" font-size: x-small;">Intermediate</td>
</tr>
<tr>
<td><span style=" font-size: x-small;">Ciprofloxacin</td>
<td><span style=" font-size: x-small;">Resistant</td>
</tr>
<tr>
<td><span style=" font-size: x-small;">Imipenem</td>
<td><span style=" font-size: x-small;">Resistant</td>
</tr>
<tr>
<td><span style=" font-size: x-small;">Gentamicin</td>
<td><span style=" font-size: x-small;">Resistant</td>
</tr>
<tr>
<td><span style=" font-size: x-small;">Tobramycin</td>
<td><span style=" font-size: x-small;">Resistant</td>
</tr>
<tr>
<td><span style=" font-size: x-small;">Amikacin</td>
<td><span style=" font-size: x-small;">Resistant</td>
</tr>
<tr>
<td><span style=" font-size: x-small;">Aztreonam</td>
<td><span style=" font-size: x-small;">Intermediate</td>
</tr>
<tr>
<td><span style=" font-size: x-small;">Cefepime</td>
<td><span style=" font-size: x-small;">Sensitive</td>
</tr>
<tr>
<td><span style=" font-size: x-small;">Meropenem</td>
<td><span style=" font-size: x-small;">Resistant</td>
</tr>
</TBODY></table>
<table>
<tr>
<th><span style=" font-size: x-small;">Tobramycin E test (not yet
FDA approved)</th>
</tr>
<tr>
<td><span style=" font-size: x-small;">MIC 32</td>
<td><span style=" font-size: x-small;">No
interpretation"</td>
</tr>
</TBODY></table>
<span style=" font-size: x-small;">What is your categorization
of this bug, and how should Jane Smith be approached regarding
infection control on a clinic visit? You wouldn't be expected to
know the answer without a lot more knowledge of how the tests are
done and what they mean. Here are several points about this culture
result:
<ul>
<li><span style=" font-size: x-small;">This bug is multiresistant.
This is because it is resistant to all tested antibiotics in 2 out
of the three 3 represented.
<ol>
<li><span style=" font-size: x-small;">The only quinolone tested
(because it has the highest and only frequently present quinolone
activity against Pseudomonas) is ciprofloxacin.
Resistant.</li>
<li><span style=" font-size: x-small;">The three aminoglycosides
tested are gentamicin, tobramycin, and amikacin. Resistant to all
three.</li>
<li><span style=" font-size: x-small;">The rest of the drugs
shown--total of 7--are beta-lactams. Of these 7 drugs, the bug is
sensitive to just one, cefepime. This sensitivity keeps the bug
from being called panresistant. But because it is multiresistant
Jane will be asked to don a mask for her clinic visit, and if
hospitalized she will have respiratory isolation procedures in
place.</li>
</ol>
</li>
<li><span style=" font-size: x-small;">Because it is multiresistant
does it mean Jane is untreatable? No! If she is sick we can start
cefepime (an iv-only drug). We would probably combine that with iv
tobramycin, because even though the report says she is resistant to
tobramycin there is synergy between these two antibiotic classes in
attacking Pseudomonas.</li>
<li><span style=" font-size: x-small;">If Jane is a little sick, or
her PFTs have dropped, we may put her on Tobi®. Why? Although the
conventional test (Kirby Bauer disc diffusion) says her bug is
resistant to tobramycin, the "E test" done at Stanford
(not commonly done elsewhere) shows the bug can be killed by
tobramycin if a concentration of 32 micrograms per milliliter
[mcg/ml] can be achieved. It is difficult to do this by iv
tobramycin without risking toxicity to kidneys or inner ear, but it
is easy to do by having Jane inhale 300 milligrams of tobramcyin
solution for inhalation-a Tobi® dose -- twice daily. This will
produce a sputum level in the neighborhood of 1,000 mcg/ml, far
above that needed to kill the bug, even after allowing for the fact
that tobramycin can lose up to 90% of its activity in CF
sputum.</li>
</ul>
<h3><span style=" font-size: x-small;">THE CONCEPT OF RESISTANCE -
A RED HERRING IN CF?</h3>
<span style=" font-size: x-small;">We have problems even defining
and understanding what resistance means in the world of CF. The
word resistance refers to lab tests done in a liquid suspension
with a conventional set "dose" of bacteria and cutoffs
between "sensitive" and "resistant" refer to
levels of that antibiotic traditionally associated with curing
systemic (i.e, blood) infections.
<span style=" font-size: x-small;">We know in CF that the
conventional term "resistance" is questionable
clinically. For example, if your Pseudomonas is called
"resistant" because tobramycin does not kill it at the
conventional testing cutoff level of 8 mcg/ml, this is not very
relevant in a disease where the bug is living in the mucus rather
than tissue or blood, and we can deliver 1,000 mcg/ml Tobi® to the
mucus by aerosol. Moreover, the way the bug lives in your lung is
as a mucoid biofilm-a gigantic communal mass of bacteria (up to one
billion bacteria in one gram of sputum!) stuck together by a slimy
material called alginate or mucoid exopolysaccharide. This is much
different than the way lab antibiotic testing is done with
individual bugs swimming around freely in liquid
suspension.
<h3><span style=" font-size: x-small;">INFECTION
CONTROL</h3>
<span style=" font-size: x-small;">We rely on universal direct and
indirect contact precautions for ALL patients to reduce
transmission of bacteria. The simplest way to describe this is to
imagine a three foot zone around your body that should ideally not
be entered by another patient (unless you live with them), and no
shared object use without proper cleaning in between. All contacts
by caregivers should be preceded by handwashing and cleaning of
multi-use instruments such as stethoscopes.
<span style=" font-size: x-small;">We are concerned about
acquisition and spread of Pseudomonas, and the infection control
measures are designed to reduce the chance of spread. For
multiresistant and panresistant bugs, we add restrictions on the
patient such as use of mask when coming to clinic, and isolation
when hospitalized. This is done to reduce the chance of
transmission, not because the patient is sicker! The mask is an
additional level of precaution but contact precautions are the key
element for ALL patients.
<span style=" font-size: x-small;">In the near future the CFF
Consensus Conference report on Infection Control will be published
and available for detailed reading.
</blockquote>