Professional Documents
Culture Documents
Infectious Diseases – 05
25/10/2021
IDSA Classification
There is separation between acute and chronic. Acute is divided between complicated and uncomplicated.
● Uncomplicated are usually easy to treat, but there are differences among them. They are divided
into primary and secondary.
● Complicated is divided into non-necrotizing and necrotizing. The importance in this division is
related to the management of the infections. Necrotizing may demand a combination of surgical
treatment and medical approach because these lesions can be lethal.
FDA Classification
It is a different classification from the IDSA, as we can see in the right side of the table. It was put by the
professor so that we know that there is more than one classification. ABSSSI means Acute Bacterial Skin
and Skin Structure Infections.
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Infectious Diseases Society of America (IDSA)
Lecture 5 Skin and Soft Tissue Infections & Clinical aspects of Bone and Joint Infections 25/10/2021
Cellulitis / Erysipelas
Definition
Cellulitis, abscess, or both are among the most common skin and soft tissue infections. Cellulitis (which
includes erysipelas) manifests as an area of skin erythema, edema, and warmth as a result of bacterial
entry via breaches in the skin barrier. A skin abscess is a collection of pus within the dermis or
subcutaneous space.
Cellulitis vs Erysipelas
Cellulitis Erysipelas
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I found this on the web to help clarify. The source is:
https://www.uptodate.com/contents/image?imageKey=ID%2F110605.
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Lecture 5 Skin and Soft Tissue Infections & Clinical aspects of Bone and Joint Infections 25/10/2021
Common factors: Etiology, risk factors , diagnosis and management of Erysipelas and Cellulitis are similar.
Most consider Erysipelas as a form of cellulitis
Immunocompromised patients: pathogens include some gram-negative bacteria, some mycobacteria, and
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Lecture 5 Skin and Soft Tissue Infections & Clinical aspects of Bone and Joint Infections 25/10/2021
cryptococcus (a fungus) and other uncommon bacteria.
Chronic kidney disease: vibrio vulnificus, vibrio alginolyticus, Neisseria meningitidis, and E. coli.
Aquatic injury: vibrio, mycobacterium, and another very particular kind of infection which is Erysipelothrix
rhusiopathiae, a typical infection after injury with the bone of a fish. At risk are fishers and workers of the
food industry.
Animal and human bite: the most important is Pasteurella which usually is a common opportunistic
infection that is present in the mouth of dogs and cats. Streptococcus, Staphylococcus and Neisseria are
also important.
Differential diagnosis
When we have a patient with a skin infection it's typical that the disease is misdiagnosed into other similar
conditions, so we have to make a differential diagnosis into other both infectious and non-infectious
conditions.
Bilateral vs unilateral: Usually infections are unilateral, because it is very difficult that the patient will
develop in the same exact moment, the same process in two different sides of the body. When we see
something that is bilateral we have to think about a systemic process, probably non-infectious. Sometimes
we can see this in a patient with chronic edema of the lower limbs, for example, in a patient with a chronic
heart failure or with cirrhosis.
Symptoms of dolor, calor, rubor and tumor are also seen in DVT and in gout: in DVT it typically involves
the legs which become dark color and this patient can also be febrile, especially if they have a
complication. One one thing that we need to do is just to check with ultrasound whether we have a
thrombosis in the lower limbs.
Biomarkers (WBC, CRP, PCT): these three can be useful to identify infectious processes versus
non-infectious processes.
Notice that age is an important factor, because it divides the patients into 2 groups with different risk
factors and comorbidities associated.
For patients younger than 65 we have to pay attention to dermatophytosis3, chronic skin ulcer, and
obesity.
For patients older than 65 there are more risks associated. Two are the same as for older patients, they are
3
From wikipedia: Dermatophytosis, also known as ringworm, is a fungal infection of the skin. Typically it
results in a red, itchy, scaly, circular rash. Hair loss may occur in the area affected. Symptoms begin four to
fourteen days after exposure. Multiple areas can be affected at a given time.
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Lecture 5 Skin and Soft Tissue Infections & Clinical aspects of Bone and Joint Infections 25/10/2021
chronic skin ulcer and dermatophytosis. The other factors are diabetes mellitus, phlebitis /
thrombophlebitis, varicose veins of the legs / lymphedema, and heart failure.
Microbiology
Microbiology is not very useful for uncomplicated skin infections and usually is not recommended. The
reason is because blood culture is positive in only 2-10% of the cases.
Treatment
Uncomplicated infections (for example: cellulitis as non-necrotizing infection)
● Amoxicillin with clavulanate with or without clindamycin.
When do we add clindamycin to the basic treatment?
This drug has a role in blocking protein synthesis, therefore blocking bacterial toxins. It can be used for
pathogens that cause severe infection, for infections that can evolve to a necrotizing process, or in cases
where the patient may suffer from toxic shock syndrome.
When do we suspect MRSA (medication resistant staphylococcus aureus) infection?
Risk factors are hemodialysis, previous colonization, and healthcare associated infection.
How do we treat MRSA suspected infections?
These pathogens are resistant to the basic treatment of amoxicillin+clavulanate. In these cases treatment
is based on other drugs: linezolid, doxycycline, trimethoprim/sulfamethoxazole.
Necrotizing fasciitis
Definition
Rapidly progressive acute infection of muscular fascia with necrosis of subcutaneous tissue. Surgical
diagnosis characterized by friability of the superficial fascia, dishwater-gray exudate, and a notable absence
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Lecture 5 Skin and Soft Tissue Infections & Clinical aspects of Bone and Joint Infections 25/10/2021
of pus (diagnosis is discussed later). It can occur after major traumatic injuries, as well as after minor
breaches of the skin or mucosa (e.g., tears, abrasions, lacerations, or insect bites), varicella infection,
nonpenetrating soft-tissue injuries.
4
This classification part of the lecture missed some context so I added extra info to make more sense. This
was taken from the MSD Manual (professional version).
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Lecture 5 Skin and Soft Tissue Infections & Clinical aspects of Bone and Joint Infections 25/10/2021
5
I couldn’t understand the professor's explanation, so I got this definition from
https://www.caister.com/cimb/v/v17/11.pdf
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Lecture 5 Skin and Soft Tissue Infections & Clinical aspects of Bone and Joint Infections 25/10/2021
This is very helpful especially if performed in the emergency room because it can predict the need of
management of the disease. A LRINEC score of 8 or greater or a LRINEC score of 6-7 plus lactate of 4 or
greater, give the indication to start managing the condition.
at 4pm at 7pm
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Lecture 5 Skin and Soft Tissue Infections & Clinical aspects of Bone and Joint Infections 25/10/2021
after a while (in the slides says 7pm again but it this was taken already during surgery (in the slides
should be wrong) says 7pm again but it should be wrong)
What we saw in this case was the involvement of the entire leg and also of the hip and unfortunately,
despite surgery and prompt antibiotic administration, that patient died from septic shock and multiple
organ failure.
Management
Timing: as we can see from the study above timing is very important to determine survival.
Surgery: it is mandatory, and it has to be performed ASAP.
Broad Spectrum antimicrobials: polymicrobial infections are possible especially in comorbid patients.
AntiMRSA agents: Daptomycin or linezolid.
AntiGram-negative: Piperacillina-tazobactam, Carbapeneme, Clindamycin.
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Lecture 5 Skin and Soft Tissue Infections & Clinical aspects of Bone and Joint Infections 25/10/2021
Fournier gangrene/Ecthyma
It is a type of necrotizing fasciitis affecting the external genitalia or perineum. It occurs on elderly,
immunocompromised, diabetic patients. Causative agents are gram-negative bacilli, Staphylococcus aureus,
Clostridia.
This picture is from a typical case, the necrosis of the perineum is very
similar to a negotiating cyclist but typically localized and external
genitalia.
Usually involve men with the mean age of 50 to 60, with a predisposing
the condition, like colorectal disease, cutaneous disease or diabetes.
As you can see in the pictures above, this is a life-threatening, impressive disease that involves the
superintendent of space and if we don't go with surgery the affection can be lethal.
Management: Hyperbaric chamber
Definition: Hyperbaric oxygen therapy involves placing the patient in an environment of increased ambient
pressure while breathing 100% oxygen, resulting in enhanced oxygenation of the arterial blood and tissues.
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Some authors suggest hyperbaric oxygen, but this is not clearly demonstrated in the clinical service so we
usually prefer to not recommend this treatment. The reason is because usually people are unstable with
septic shock and need intensive care treatment, and if the patient goes to the hyperbaric oxygen, which is
usually far from the hospital, they will probably receive less intensive treatment.
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https://jamanetwork.com/journals/jamasurgery/fullarticle/397749
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Lecture 5 Skin and Soft Tissue Infections & Clinical aspects of Bone and Joint Infections 25/10/2021
IDSA guidelines 2014: “Hyperbaric oxygen (HBO) therapy is not recommended because it has not been
proven as a benefit to the patient and may delay resuscitation and surgical debridement (strong, low)”.
Management: Antibiotics
There are 2 approaches depending on the degree of suspicion of NF, done by assessing risk factors, clinical
features, and sepsis/septic shock.
1) Low suspicion for NF (non life-threatening)
a) Amoxicillin-Clavulanate ev
b) Clindamycin ev
2) Suspected NF (life-threatening)
a) Daptomycin
b) Meropenem
c) Clindamycin
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Lecture 5 Skin and Soft Tissue Infections & Clinical aspects of Bone and Joint Infections 25/10/2021
This patient is cirrhotic, has uncompensated diabetes, and hypopituitarism in chronic steroid therapy. This is
a Mucormycosis caused by a common mold named Rhizopus spp. This is a very important and life
threatening infection, typical of immunocompromised patients and diabetic patients.
Case: Fusiliosis in a young neutropenic lady with Acute Myeloid Leukemia (AML)
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Lecture 5 Skin and Soft Tissue Infections & Clinical aspects of Bone and Joint Infections 25/10/2021
If we see the causes of bite and scratch injuries by animals we can see that dogs are involved in 63% of
cases, cats 25% and other domestic 9%. Wild and zoo animal bites are much more uncommon.
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Lecture 5 Skin and Soft Tissue Infections & Clinical aspects of Bone and Joint Infections 25/10/2021
According to the factors related to the dog bites, usually working, and sporting dogs, or having activity with
dogs are risk factors. The dogs that cause bites are usually male and pure breed.
There are important cause of bites to all solar dogs so the owner of the dog can be involved very frequently
but usually in most cases in our neighbor neighborhood
Severe infection can be related to dog and cat bites and in 20% of cases these include deep abscesses and
osteomyelitis. Osteomyelitis and deep abscesses are more common with cat bites, they have very thin and long teeth so
the bite, especially when involved the hands, can go directly to the body.
Microbiology
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Lecture 5 Skin and Soft Tissue Infections & Clinical aspects of Bone and Joint Infections 25/10/2021
Remember that any vertebrate can have Clostridium tetani, which is important for immune prophylaxis.
Any mammal can spread rabies.
The most important pathogens involved in dog bites are Pasteurella multocida.
In cats, Pasteurella multocida is the pathogen involved in the cat scratch disease.
Infection caused by rats which is Streptobacillus moniliformis.
When we have fresh water involvement, we have Aeromonas hydrophila.
When we have the involvement of the saltwater species we have to remember Vibrio vulnificus and
Mycobacterium marinum.
The last is a very rare disease caused by a virus named Herpesvirus simiae (B virus) which is usually
involved in macaque bites. This causes a certain malignant encephalitis that can be very very difficult to
diagnose and to treat and lethal.
Rat bite
Rat bite is atypical, and it can spread certain pathogens. Symptoms usually begin 3 to 10 days after the
bite but can be delayed as long as 3 weeks. By this time, any rodent bite or scratch wound that caused the
infection has usually healed.
Symptoms:
● Fever
● Vomiting
● Headache
● Muscle pain, joint pain or swelling (59%)
● Rash (occurs in about 3 out of 4 people with RBF 2-4
days after fever – hand and feet palm/soles)
When we have a skin rash that involves the palms and soles of
hands and feet we have to remember several diseases but one
of these is the rat bite, that is caused by Streptobacillus
moniliformis.
● Rat-bite fever.
● Haverhill fever, an infection that is acquired through ingestion of the organism.
● Erythema arthriticum epidemicum, a migratory polyarthritis or arthralgia.
When do we have to give antibiotics for mammalian bites? This is a meta-analysis from several studies
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Lecture 5 Skin and Soft Tissue Infections & Clinical aspects of Bone and Joint Infections 25/10/2021
that were performed to assess whether or not to give antibiotics. Usually, the indication is to give
antibiotics in human bites in all cases. In case of any bites that involve hands and face. The face because it
is more risky for infection and because the infection can have an aesthetic outcome.
The hands are at higher risk of infection especially when they are caused by cat bites, probably because the
hands are typically more colonized with the other pathogens and in the hands the bones are very near the
skin and cat bites can go deep to the bone, so in these cases we prefer to treat with antibiotics even as a
prophylaxis.
Rabies Prophylaxis
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Lecture 5 Skin and Soft Tissue Infections & Clinical aspects of Bone and Joint Infections 25/10/2021
Bone is a less vascularized tissue than, for example, the lungs or skin. The composition of bone is different
from that of other tissues, and it is difficult to predict whether agents showing good penetration into other
tissues will also achieve high concentrations in bone. That is one of the reasons why the treatment of skin
for bone infection is more complicated than other kinds of infections.
Biofilm
OUR WORST ENEMY
The Biofilm: a Secret Refuge of the Microbial World
A bacterial biofilm is defined as a structured community of
sessile bacterial cells enclosed in a self-produced polymeric
matrix, adherent to an inert or living surface, within which
the bacteria metabolically cooperate to protect themselves in
a hostile environment.
Sessile (or stationary) forms are characterized by slower
cellular division.
The concentration of antibiotic required to inhibit the growth
of bacteria in biofilms can be up to 1000-fold higher with the
planktonic phenotype (form characterized by rapid cellular division).
When we use antibiotics to treat biofilm related infection, we need to know, that the extracellular matrix
protects the microbes and the metabolism of bacteria is slower, and when we have drugs that in somehow
alter the metabolism of bacteria, if the metabolism is slower, the ability to kill is lower.
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Lecture 5 Skin and Soft Tissue Infections & Clinical aspects of Bone and Joint Infections 25/10/2021
Formation of biofilms
Biofilm formation is not very fast, it usually takes some days to develop, and some in certain cases
also several weeks.
Guidelines
When we think about skin or bone and joint infection, we must face the fact that there are no
common guidelines. This is the only guideline that was produced in the last years, so it's very
difficult for the clinician to have a guide to manageme these processes.
Psychological problems
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Lecture 5 Skin and Soft Tissue Infections & Clinical aspects of Bone and Joint Infections 25/10/2021
Typically, patients with bone and joint infections are patient with the with history of a higher number of
failure of treatments. For example, in Bologna, we have a specialized team for bone and joint infection and
we collect cases from all over Italy. In these cases, usually people face a very high number of failure before
uh to go to a specialized center.
Therapy
The treatment of this condition usually involves surgery (if specialized on treating bone infection is even
better) and antibiotic treatment.
But despite advances in surgical medical management, osteomyelitis, and general bone infections, are still
considered one of the most difficult to treat infectious diseases.
Usually, bone infections are not life-threatening because these infections are caused by slow growing
pathogens, very localized. And if we have a very poor vascularized tissue it is very difficult to treat but at
the same time it is very difficult for the infection to spread to other organs, and that is why we don’t have
cases of septic shock, multiple organ failure or death.
Pathogenesis
The pathogenesis is due to 2 typical mechanisms:
1. Direct inoculation of microorganisms into the bone because of trauma and surgery. For example,
if we have a patient that receives a hip prosthesis, during surgery there can be direct inoculation of
slow growing pathogens and after weeks or months we can develop an infection.
2. Hematogenous. In this case, we have a trauma or inoculation of pathogens on the other side of the
body but with a hematogenous route it will localize in the bone.
Classification
There are two major osteomyelitis classification schemes:
1) Cierny and Mader classified osteomyelitis based on the affected portion of the bone, the
physiologic status of the host and the local environment.
2) Lew and Waldvogel classified osteomyelitis based on the duration of illness (acute vs chronic), the
mechanism of infection (hematogenous vs contiguous), and the presence of vascular insufficiency:
is an etiologic classification and does not implicate a specific therapeutic strategy
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Lecture 5 Skin and Soft Tissue Infections & Clinical aspects of Bone and Joint Infections 25/10/2021
In this stage, the medullary part of the bone is typically involved as we can see on the CT scan.
Stage III, which is a localized osteomyelitis, involve both medullary and superficial part of the bone.
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Lecture 5 Skin and Soft Tissue Infections & Clinical aspects of Bone and Joint Infections 25/10/2021
Stage IV, or diffuse osteomyelitis, in which the structure of the bone is completely changed.
Multidisciplinary team
In 1944, with the introduction of penicillin, John Albert Key, wrote: “continuous drug over a long period
time will lessen the amount of discharge, but it will not cure the disease because it cannot sterilize dead
bone or cavities with necrotic content and rigid walls”.
Even after the introduction of penicillin it was clear that only drugs cannot sterilize all the bone cavities
and necrotic content, so it became clear that the management of this infection should include both
surgeon and infectious disease specialists.
Essential is the strong collaboration between all involved medical and surgical specialists (eg, orthopedic
surgeons, radiologists, neurosurgeons, infectious disease specialists, pain specialists, microbiologists,
pharmacologists…).
Chronic osteomyelitis
It manifests in 3 forms:
1) Spondylodiscitis: it is osteomyelitis on the spine and it usually involves the lumbar part of the spine
but it can involve any kind of vertebrae. It can be both pyogenic (means that usually involve
staphylococci, streptococci, etc) or granulomatous (these are usually caused by tuberculosis, and in
this case it can be called pot disease, or can be caused by Brucella).
2) Osteomyelitis after septic arthritis: an infection that occurs after the penetration of pathogen into
the joint cavity and prosthesis infection. It occurs only in 0.2-0.5 percent of cases but when it
happens morbidity is very high.
3) Osteomyelitis and delayed JPI (joint prosthesis infection)
Management
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Lecture 5 Skin and Soft Tissue Infections & Clinical aspects of Bone and Joint Infections 25/10/2021
When we have a vertebral osteomyelitis, the initial management of patients should include:
1) MRI with contrast
2) Sometimes vertebral biopsy, especially if blood cultures are negative. This is important if you want
to exclude non-common diseases such as tuberculosis and Brucella.
3) Blood tests
4) Orthopedic visit for indication for surgery.
5) Pain therapist.
Delayed PJI
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Lecture 5 Skin and Soft Tissue Infections & Clinical aspects of Bone and Joint Infections 25/10/2021
When we have a delayed infection the probability of biofuel formation is lower so we can try to just do
debridement, doing just one surgical intervention and then the probability of saving the prosthesis is
higher.
When a joint has become distended with pus, if it is freely opened and copiously irrigated, it may forthwith
undergo a startling improvement and, if the patient survives, may completely recover and retain absolutely
free movement.
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Lecture 5 Skin and Soft Tissue Infections & Clinical aspects of Bone and Joint Infections 25/10/2021
This is the theoretical penetration of antibiotics into the bones of several drugs. Usually, most of these
drugs have an activity against MRSA.
Notice that Vancomycin, which was one of the main drugs in the past, has a very poor penetration of the
bone, only 14%.
Linezolid has a much higher penetration, but prolonged administration can cause problems because of the
side effects that include bio suppression, peripheral neuropathy, and others.
Levofloxacin is a very good agent; it has 77% of penetration to the bone and it has a good bio availability.
Rifampin is another good treatment; it is an antibiotic that can be used for treatment of tuberculosis but in
combination with some other drugs it can be very useful since it has very good biofilm penetration.
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Lecture 5 Skin and Soft Tissue Infections & Clinical aspects of Bone and Joint Infections 25/10/2021
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