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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

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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

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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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• 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.

Learning pearl

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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 40°C (axillary)

• Copious amounts of yellow-green secretions are suctioned from his endotracheal tube.

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sinus tachycardia with no rubs or murmurs.

The abdomen is distended and F.R. complains of new abdominal pain.

No bowel sounds can be heard and the stool is guaiac positive.

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/high-power field

Physical examination reveals

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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 and after eating.

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Labs

• (WBC/HPF), few casts • Glucose 320 mg/dL (normal, 70–110);

• Specific gravity of 1.015 • Serum albumin, 2.1 g/dL (normal, 4–6);

• Sodium, potassium normal ,Chloride 110 mEq/L (normal, 95–105)

• CO2 16 mEq/L (normal, 22-32)

• Hemoglobin (Hgb), 10.3 g/dL; hematocrit (Hct), 33% (normal, 39%–49% [male patients]);

• (ESR), 65 mm/hour (normal, 0–20). • WBC count, 15,600/mm3 with bands present; platelets, 40,000/mm3 (normal, 130,000–400,000);

• BUN, 58 mg/dL (normal, 8–18) • Prothrombin time (PT), 18 seconds (normal, 10–12);

• Creatinine, 3.8 mg/dL (increased from 0.9 mg/dL at admission) (normal, 0.6–1.2);

• Blood, tracheal aspirate, and urine cultures are pending

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

2-Establishing the Presence of an Infection

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Signs and symptoms consistent with an infectious process

Signs & Symptoms Explanation

WBC count (15,600/mm3) and a “shift to the left” (bands are present on the differential).

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 40°C by axillary measurement.

Fever is a common manifestation of infection, with oral temperatures generally >38°C. Oral and axillary temperatures tend to be approximately 0.4°C lower compared with rectal measurement. As a result, F.R.'s temperature would be expected to be 40.4°C 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 <36°C.

Erythema surrounding his central venous catheter

Infectious process

Copious amounts of yellow-green secretions from his endotracheal tube,

Infectious process

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 pearl1. 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 colony-stimulating 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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Septic shock Intense vasodilation

Normal SVR of 800 to 1,200

dyne.sec.cm-5 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

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

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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 (30–70 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.