Principles of Infectious Diseases-1

By Dr Muhammad Junaid Hassan

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Outline

1-Approaching the problem

2-Establishing the Presence of an Infection
3-Establishing the Severity of an Infection
4-Problems in the Diagnosis of an Infection
5) Establishing the Site of the Infection
6-Determining Likely Pathogens
7) Microbiologic Tests and Susceptibility of Organisms
8-Determination of Isolate Pathogenicity

Outline
9-Antimicrobial toxicities
10-Antimicrobial Costs of Therapy
11-Route of Administration
12-Antimicrobial Dosing
13-Pharmacokinetics/ Pharmacodynamics
14-Antimicrobial Protein Binding
15- Antimicrobial treatment failure

1-Approaching the problem

The proper selection of antimicrobial therapy is based on
several factors.
Establish the presence of an infectious process because
several disease states (e.g., malignancy, autoimmune
disease) and drugs can mimic infection.
Identify the site.
Signs and symptoms (e.g., erythema associated with
cellulitis) direct the clinician to the likely source.
Because certain pathogens are known to be associated
with a specific site of infection, therapy often can be
directed against these organisms.
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Learning pearl
Erythema is redness of the skin, caused by
hyperemia of the capillaries in the lower layers
of the skin.
It occurs with any skin injury, infection, or
inflammation
Hyperaemia or hyperemia is the increase of
blood flow to different tissues in the body.
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1-Approaching the problem

Additional laboratory tests, including the Gram stain,
serology, and antimicrobial susceptibility testing
identify the primary pathogen.
Antimicrobials potentially considered based on their;
spectrum of activity,
clinical efficacy,
adverse effect profile,
pharmacokinetic disposition,
cost considerations.
Dosage must be based on the size of the patient, site of
infection, route of elimination, and other factors.
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Case based Pharmacotherapy approach

F.R., a 65-year-old man in the intensive care unit, underwent
emergency resection of his large bowel. He has been intubated
throughout his postoperative course.
On day 20 of his hospital stay, F.R.
Presenting complaint

Suddenly becomes confused

BP drops to 70/30 mmHg

Circumoral pallor

Heart rate of 130 beats/minute

Extremities are cold to the touch

Respiratory rate is 24
breaths/minute

His temperature increases to 40C

(axillary)

Copious amounts of yellow-green

secretions are suctioned from his
endotracheal tube.
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Physical examination reveals

sinus
tachycardia
with no
rubs or
murmurs.

No bowel
sounds can be
heard and the
The abdomen stool is guaiac
is distended positive.
and F.R.
complains of
new
abdominal
pain.

Urine output
from the Foley
catheter has
been 10
mL/hour for the
past 2 hours.

Erythema is noted
around the central
venous catheter.
A chest radiograph
reveals bilateral lower
lobe infiltrates, and
urinalysis reveals >50
white blood cells/highpower field

Learning pearl
Abdominal sounds (bowel sounds) are made by the movement of the
intestines as they push food through. Since the intestines are hollow,
bowel sounds can echo by listening to the abdomen with a stethoscope
(auscultation).
Reduced (hypoactive) bowel sounds include a reduction in the loudness,
tone, or regularity of the sounds. They are a sign that intestinal activity
has slowed.
Hypoactive bowel sounds are normal during sleep, and also occur
normally for a short time after the use of certain medications and after
abdominal surgery.
Decreased or absent bowel sounds often indicate constipation.
Increased (hyperactive) bowel sounds can sometimes be heard even
without a stethoscope. Hyperactive bowel sounds mean there is an
increase in intestinal activity. This can sometimes occur with diarrhea
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and after eating.

Labs
(WBC/HPF), few casts
Specific gravity of 1.015
Sodium, potassium normal ,Chloride
110 mEq/L (normal, 95105)
CO2 16 mEq/L (normal, 22-32)

Glucose 320 mg/dL (normal, 70

110);
Serum albumin, 2.1 g/dL (normal, 4
6);
Hemoglobin (Hgb), 10.3 g/dL;
hematocrit (Hct), 33% (normal, 39%
49% [male patients]);

(ESR), 65 mm/hour (normal, 020).

WBC count, 15,600/mm3 with bands

present; platelets, 40,000/mm3
(normal, 130,000400,000);
BUN, 58 mg/dL (normal, 818)
Prothrombin time (PT), 18 seconds
(normal, 1012);
Creatinine, 3.8 mg/dL (increased from Blood, tracheal aspirate, and urine
0.9 mg/dL at admission) (normal,
cultures are pending
0.61.2);
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2-Establishing the Presence of an Infection

Which of F.R.'s signs and symptoms are
consistent with infection?

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Signs and symptoms consistent with an

infectious process
Signs & Symptoms
WBC count
(15,600/mm3) and a
shift to the left
(bands are present on
the differential).

Explanation
Increased WBC count commonly is observed with infection,
particularly with bacterial pathogens.
Shift to the left (i.e., presence of immature neutrophils), suggesting
that the bone marrow is responding to an infectious insult.
In less acute infection (e.g., uncomplicated urinary tract infection,
abscess), the WBC count may remain within the normal range.
Because the abscess is a localized lesion, less bone marrow
response would be anticipated; thus, the WBC count may not
increase in these patients.
An increased Infection is not always associated with leukocytosis,
however. Overwhelming sepsis can cause a decreased WBC count;
some patients become neutropenic secondary to infection.
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Signs & Symptoms

Explanation

Temperature is 40C by
axillary measurement.

Fever is a common manifestation of infection, with oral

temperatures generally >38C.
Oral and axillary temperatures tend to be approximately 0.4C
lower compared with rectal measurement. As a result, F.R.'s
temperature would be expected to be 40.4C if his temperature
had been taken rectally. In general, rectal measurement of
temperature is a more reliable determination of fever. Some
patients with overwhelming infection, however, may present with
hypothermia and temperatures <36C.

Erythema surrounding his

central venous catheter

Infectious process

Copious amounts of
Infectious process
yellow-green secretions
from his endotracheal tube,
Bilateral lower lobe
infiltrates on chest
radiograph,

Infectious process

F.R. has the signs and symptoms that also are consistent with sepsis
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3-Establishing the Severity of an Infection

What signs and symptoms manifested by F.R.
are consistent with a serious systemic
infection?

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Learning pearl
1. Bacteremia: presence of bacteria in blood. May or may not cause
any symptoms
2. Viremia: presence of virus in blood
3. Septicemia: also presence of bacteria in blood but this is an
infection that moves rapidly and is life threatening.
. Characterized by different processes, toxemia, bacteremia, septic
inflammatory response syndrome (SIRS).
. May result from kidney infection, pneumonia, meningitis,
endocarditis, osteomyelitis etc.
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 Symptoms includes; high fever, chills, rapid pulse, rapid

breathing, confusion, hypotension, decreased urine output.
Septicemia may progress to respiratory distress syndrome, septic
shock and death.
4. Sepsis: It is a whole body inflammation state. An immune system
response to a serious infection.
symptoms include high fevers, hot, flushed skin, elevated heart
rate, hyperventilation, altered mental status, swelling, and low
blood pressure.
5. Septic shock: is a condition as a result of severe infection and
sepsis, causing multiple organ dysfunction syndrome (formerly
known as multiple organ failure) and death.
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Bacteremia

Septicemia

Sepsis

Septic
shock

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The sepsis cascade. ARDS, acute respiratory distress syndrome; ARF, acute renal failure;
DIC, disseminated intravascular coagulation; GM-CSF, granulocyte macrophage colonystimulating factor; IL-1, interleukin-1; IL-6, interleukin-6; PAF, platelet activating factor;
TNF, tumor necrosis factor.
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a) Hemodynamic Changes

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 Critically ill patients often have central intravenous (IV) lines in place for
measuring cardiac output and systemic vascular resistance (SVR).

Septic shock

Intense vasodilation

Normal SVR of 800

to 1,200 dyne.sec.cm5
fall to 500 to 600
dyne.sec.cm-5

Increased Heart rate

(Reflex Tachycardia)

Stress-induced
catecholamine
release leading to
arterial
vasoconstriction

Increased cardiac
output from its
normal 4 to 6
L/minute to as much
as 11 to 12 L/minute

Insufficient to
overcome the
vasodilatory state,
and hypotension
ensues

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In overwhelming septic
shock, myocardial
depression results in a
decreased cardiac
output.

Decreased cardiac
output + decreased SVR
results in hypotension
unresponsive to
pressors and IV fluids.

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Patient findings
F.R. has hemodynamic evidence of septic
shock.
He is hypotensive (BP 70/30 mmHg) and
tachycardia (130 beats/minute), presumably in
response to significant vasodilation and
catecholamine release.

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Normal urine output of

approximately 0.5 to 1.0
mL/kg/hour (3070 mL/hour for
a 70-kg patient) can decrease to
<20 mL/hour in sepsis.
The urine output for F.R. has
decreased to 10 mL/hour,
consistent with sepsis-induced
perfusion abnormalities.

F.R.'s uremia (BUN 58 mg/dL)

and increased serum creatinine
concentration (3.8 mg/dL) are
consistent with decreased renal
perfusion secondary to sepsis.

Decreased blood flow to the liver

may result in shock liver, in
which LFTs become elevated.
LFTs are not available; however,
his serum albumin concentration
is low (2.1 g/dL) and his PT of 18
seconds is prolonged.

Decreased blood flow to the

musculature is characterized by
cool extremities, and decreased
blood flow to the brain can result
in decreased mentation.
F.R. is confused, his extremities
are cold, and the area around his
mouth appears pale.
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 All these signs and symptoms provide

strong evidence that he is in septic
shock.

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