Загрузил Tony Cham

Skin and Soft Tissue Infections

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Second problem: Skin and Soft Tissue Infections
The patient was a 45-year-old male who was in his usual state of good health when he awoke at
3am with pain in the lateral aspect of his left calf. He looked at his calf and thought that the pain
was due to an ingrown hair and went back to sleep. At 10am, he expressed a small amount of
pus from the ingrown hair. Over the next 8h, the patient developed an area of cellulitis on the
lateral aspect of the calf of approximately 5 to 10 cm. At that time, a small amount of pus was
again extended from just below the knee to just above the ankle. The patient visited his
physician. His vital signs at that visit, including pulse, respirations, blood pressure, and
temperature, were all within normal limits.
Physical exam was significant for an area of obvious fluctuant. No lymphadenopathy was
observed. The central area of the cellulitis, near the area that the patient described as where the
ingrown hair had been, was punctured three tirnes, but no pus was drained. The patient was
referred to the surgery service. The surgeons examined the patient and said they would follow
him. The patient was given 2g ceftriaxone IM and begun on oral cephalexin.
The patient returned to the surgical clinic 48 hours later with an obvious area of fl uctuance in
the center of the area of cellulitis. Over the preceding 48 hours, the patient reported
low-grade fevers. Approximately 1 ml of pus was aspirated and was sent for Gram stain and
culture (Fig. 36.1 and 36.2). When pus was aspirated from the lesion, the surgeon decided to
excise and drain the lesion (Fig. 36.3).
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The Aim:
●
Knowledge of the microorganisms involved into the Skin, Soft tissue, Bone & Joint
infections: microbiology, pathogenesis, epidemiology, laboratory diagnosis, treatment,
prevention and control
The plan of self-directed learning:
●
●
Bacteria (S. aureus, S. pyogenes, H influenza, E. aerogenes, M. tuberculosis):
microbiology, pathogenesis, epidemiology, laboratory diagnosis, treatment, prevention
and control .
Fungi (B. dermatitidis, C. neoformans): mycology, pathogenesis, epidemiology,
laboratory diagnosis, treatment, prevention and control
What is the organism most likely causing this patient’sinfection? What other type of infections
does this organism
How do you think he became infected with this organism?
Why were incision and drainage necessary to treat thisinfection? Why would antimicrobial
agents alone not be
1.
Describe what you observed in
Fig. 36.1 and 36.2. The organism is catalase and coagulase
positive. What organism was
causing his infection?
2.
Why were incision and drainage necessary to treat this
infection? Why would antimicrobial agents alone not be
effective in treatment of this
infection?
3.
Susceptibility results for this
organism are seen in Fig. 36.4.
How do you interpret these
susceptibility results? Explain the likely reasons for the results seen with drugs 2 and 4.
How do results
of the testing of drug 2 explain the progression of his infection despite a
large intramuscular dose of ceftriaxone followed by oral cephalexin?
Also explain the fi ndings for drugs 7 and 8. How should the isolate
infecting this patient be treated?
4.
What test is being used to test vancomycin (drug 5)? Why is this test
being used and what does it show?
5.
What virulence factor is particularly associated with skin and soft tissue
infections (SSTIs)? Explain its mechanism of action. This virulence factor and this type of antibiogram are associated with a particular strain of
this organism. Briefl y discuss the evolving epidemiology of this strain.
6
What infection control precautions would be necessary for this patient?
What are some of the potential unintended consequences of hospitalized patients who are colonized with this organism?
7.
Why are these organisms viewed as a global threat?
CASE DISCUSSION
1.
The finding of Gram-positive cocci in clusters on Gram stain is
consistent with staphylococci. The fi nding of a yellowish colony that is
beta-hemolytic on 5% sheep blood agar is consistent with
Staphylococcus
aureus
. The staphylococci are divided into two groups based on the biochemical test
called the coagulase test;
S. aureus
is positive, while a group of >30 other staphylococcal
species are negative. This group of organisms is referred to as the
coagulase-negative
staphylococci (CoNS). Three of the CoNS species are frequently encountered clinically.
Staphylococcus epidermidis
can infect implanted foreign bodies, such as pacemak-
ers, cerebrospinal fl uid shunts used to treat hydrocephalus, intravascular catheters,
and artifi cial joints.
Staphylococcus lugdunensis
has been associated with skin and soft
tissue infections (SSTIs) as well as native valve endocarditis. Although
S. lugdunensis
can cause SSTIs, it is less common than
S. aureus
. The other frequently encountered
CoNS species is
Staphylococcus saprophyticus
, which causes urinary infections primarily
in young, sexually active women. The isolate recovered from this patient was coagulase positive and was identifi ed as
S. aureus
.
The patient’s infection began as a folliculitis at the site of the ingrown hair, progressed to a cellulitis, and ultimately evolved into an abscess. Approximately 20%
of
adults are chronic nasal carriers of
S. aureus
, while an additional 60% may carry the
organism intermittently. From the nose, the skin can become colonized. Studies
have
shown intermittent skin carriage rates as high as 40%, although most studies target the
skin carriage rate at 10 to 15%. In all likelihood this individual’s initial folliculitis was a
result of the infecting
S. aureus
coming from skin colonization. Manipulation of the skin
resulted in the spread of the organism to the dermis, leading to cellulitis and
abscess
formation.
2.
The standard of care for an abscess is 2-fold: incision and drainage (Fig. 36.3) and
antimicrobial therapy. The reason why antibiotics alone would not be suffi cient is that
abscess formation results in a loss of blood fl ow to the center of the infected area (the
abscess). As a result, antibiotic levels in the center of the abscess would be low or, in a
large abscess, completely absent, allowing the survival of the infecting organisms present there. Incision and drainage removes a large number of organisms and reduces the
infected area, making penetration of much higher levels of antimicrobial agents to the
infected tissue and killing of the infecting organism more likely.
Staphylococcus
3.
The susceptibility test that was performed on this patient is a disk diffusion test for
seven drugs and an E-test for one drug. The basis for disk diffusion susceptibility testing
is described in the introductory chapter of this text, and the reader is referred
there for
further details. The antibiogram for this organism is as follows:
Drug 1: trimethoprim-sulfamethoxazole, to which the organism is susceptible
Drug 2: cefoxitin, to which the organism is resistant
Drug 3: doxycycline, to which the organism is susceptible
Drug 4: penicillin G, to which the organism is resistant
Drug 5: vancomycin with an MIC of 2 μg/ml by E-test (see answer 3 for more details)
Drug 6: gentamicin, to which the organism is susceptible
Drug 7: clindamycin, to which the organism is susceptible
Drug 8: erythromycin, to which the organism is resistant
This
S. aureus
strain is expressing two different resistance mechanisms against the
β
-lactam
drugs. One is evidenced by its resistance to penicillin G. This resistance is due to
the
organism’s ability to produce an enzyme,
β
-lactamase, that degrades the
β
-lactam ring of
penicillin G, rendering this and the related widely used antimicrobials ampicillin,
amoxicillin, and piperacillin inactive. Approximately 90 to 95% of
S. aureus
strains
produce a
β
-lactamase that is encoded on the bacterial chromosome. Almost as soon
as penicillin G was put into widespread therapeutic use, recognition of
S. aureus
strains resistant to penicillin G by virtue of
β
-lactamase production emerged. New
agents including penicillinase-stable penicillins (oxacillin, nafcillin, and the oral
agent
dicloxacillin); first-, second-, and third-generation cephalosporins; and carbapenems were
developed over the following decades. A characteristic all these drugs shared was that
they
were relatively stable in the presence of
β
-lactamase-producing
S. aureus
. However, a second resistance mechanism to
β
-lactam drugs soon emerged. The presence of this resistance is predicted by the cefoxitin result. Although cefoxitin is not a drug that is used to
treat
S. aureus
infections,
S. aureus
strains expressing cefoxitin resistance predictably have
alteration of a specific penicillin-binding protein, PBP2. The altered
penicillin-binding
protein, PBP2a, is encoded by
mecA
. All
β
-lactam antimicrobials have significantly reduced
affinity for PBP2a relative to PBP2. This altered affinity is the basis for what we call
methicillin resistance in
S. aureus
. This term is obviously a bit of a misnomer since this PBP
alteration confers resistance to all
β
-lactam drugs, just not methicillin. The reason the
term “methicillin-resistant
S. aureus
,” or MRSA, became widespread is that methicillin
was the drug used to treat serious
S. aureus
infections when this resistance was first
encountered. It is critical to remember that no
β
-lactam antimicrobial has clinical efficacy
against MRSA with the exception of a newly developed cephalosporin, ceftaroline,
although some
β
-lactams may appear to have activity against
S. aureus in vitro
.
The only other antimicrobial to which this isolate is resistant is erythromycin. If the
placements of the clindamycin (disk 7) and erythromycin (disk 8) disks are closely examined, it should be noted that they are closer together than the other disks in order
to
determine whether there is formation of a D-shaped zone of inhibition around the clinGilligan_Sec4_255-306.indd 264
7/24/14 11:44 AM
damycin. The D-zone occurs when erythromycin induces the production of an
rRNA
methylase encoded by the
erm
gene. Expression of this methylase can be either constitutive (always on) or inducible (on only in the presence of an inducer such as
erythromycin).
erm
-specific methylation of the rRNA results in both erythromycin and clindamycin
resistance. The D-zone test is assessing whether the inducible form of
erm
is present. The
bacteria growing closest to the erythromycin disk are in the presence of an inducer, and
therefore will be resistant to clindamycin; this resistance causes a “flattening” of the zone
of inhibition in the area between the two disks, creating a characteristic D-shaped
zone
around the clindamycin disk (Fig. 36.3). If the constitutive form of
erm
was present, the
organism would test as resistant to clindamycin independent of the presence of erythromycin. Clinical failures of clindamycin therapy for infections due to
S. aureus
strains with
inducible
erm
genes are well documented in the literature. Mild SSTIs can be treated with
oral antimicrobials. Because his isolate was resistant by virtue of altered PBPs to both of
the drugs he was given initially, ceftriaxone and cephalexin (an oral
cephalosporin), this
patient next was given oral clindamycin. Some studies suggest that incision and drainage
is all that is necessary to clear the infection, but the physician was being cautious.
4.
Vancomycin is a key drug in treating MRSA infections, particularly severe ones
as
seen in this patient. Vancomycin (drug 5) is being tested using a special
antimicrobialimpregnated strip called an E-test. The strip is designed to release a gradient of a specific
antimicrobial agent into the agar. The point where the elliptical zone of bacterial growth
inhibition (thus the name “E-test”) meets the strip determines the MIC of the antimicrobial for the organism being tested. The vancomycin MIC is 2 μg/ml, which is at the upper
level of susceptibility for this organism. Strains with vancomycin MICs of 4 or 8 μg/ml
are
referred to as vancomycin-intermediate
S. aureus
, or VISA, and are more likely to result
in treatment failures. VISA strains are not reliably detected by disk diffusion techniques;
thus the need for a MIC technique. The reduced susceptibility of VISA isolates is due to
a thickening of the cell wall, resulting in “trapping” of vancomycin, a large, highly
charged
molecule. VISA strains should not be confused with vancomycin-resistant
S. aureus
, or
VRSA. VRSA strains are still quite rare worldwide. Their resistance is due to the acquisition of the
vanA
gene from
Enterococcus faecium
. VRSA strains have high-level vancomycin
resistance (MICs of 16 to ≥128 μg/ml).
5.
Panton-Valentine leukocidin is a virulence factor that is specifically associated
with
SSTIs. It is a cytolytic pore-forming hexameric protein that can lyse a variety of cell
types.
It has particular affinity for polymorphonuclear cells and macrophages (thus the
name
“leukocidin”). With increasing frequency,
S. aureus
strains with a specific molecular signature have been documented to be responsible for significant SSTIs causing
individuals to
seek care in emergency departments. These strains are called community-associated
MRSA,
or CA-MRSA. CA-MRSA strains carry the
lukS-PV
and
lukF-PV
genes encoding PantonValentin leukocidin and a small staphylococcal chromosomal cassette (SCC
mec
type IV) that
harbors
mecA
. Among CA-MRSA isolates, a specific pulsed-field gel electrophoresis pattern
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