A SEMINAR ON LOWER RESPIRATORY TRACT INFECTIONS Submitted to: B.P. Satish Kumar Assistant.Professor Submitted by: P.Deepak Pharm D (P.B) 1st Yr

ACUTE BRONCHITIS DEFINITION : Acute bronchitis or chest cold, is a condition that occurs when the bronchial tubes in the lungs become inflamed. The bronchial tubes swell and produce mucus, which causes a person to cough. This often occurs after an upper respiratory infection like a cold. Most symptoms of acute bronchitis (chest pain, shortness of breath, etc.) last for up to 2 weeks, but the cough can last for up to 8 weeks in some people.

PATHOGENESIS Acute bronchitis is a self limiting illness. Infection of trachea and bronchi produce hyperemic and edematous mucous membranes with an increase in bronchial secretions which can become thick and tenacious impairing mucociliary activity. Recurrent respiratory infections may be associated with increase airway hyperreactivity and leads to pathogenesis of asthma and COPD.

Causes of Bronchitis Several types of viruses, most often: Respiratory syncytial (sin-SIH-shull) virus (RSV) Adenovirus Influenza Parainfluenza Bacteria, in rare cases Pollutants (airborne chemicals or irritants)

CLINICAL PRESENTATION Signs and Symptoms : Cough persisting > 5 days to weeks Coryza,sore throat,malaise,headache Fever rarely > 39○c Physical examination : Rhonchi or coarse Purulent sputum in 50% of patients

PHARMACOLOGICAL THERAPY Mild analgesic or antipyretics therapy is helpful in removal of malaise , lethargy and fever. Aspirin – 650 mg in adults or 10-15 mg/kg in children Ibuprofen – 200-800 mg in adults or 10 mg/kg in children.

Chronic Bronchitis Definition: Chronic bronchitis is defined as chronic cough and expectoration. Excessive tracheo bronchial mucus production sufficient to cause cough with expectoration for most days of at least 3 months of the year for 2 consecutive years. Etiology: The most important etiologic factor in the development of chronic bronchitis is cigarette smoking.

CHRONIC BRONCHITIS Classification: Simple chronic bronchitis Chronic mucopurulent bronchitis Chronic bronchitis with obstruction Chronic bronchitis with obstruction and airway hyperreactivity.

CHRONIC BRONCHITIS PATHOPHYSIOLOGY : Chronic inflammation Hypertrophy & hyperplasia of bronchial glands that secrete mucus Increase number of goblet cells Cilia are destroyed

Chronic Bronchitis Pathophysiology Narrowing of airway Starting w/ bronchi  smaller airways airflow resistance work of breathing Hypoventilation & CO2 retention  hypoxemia & hypercapnea

Chronic Bronchitis Pathophysiology Bronchospasm often occurs End result Hypoxemia Hypercapnea Polycythemia (increase RBCs) Cyanosis Cor pulmonale (enlargement of right side of heart)

Chronic Bronchitis: Clinical Manifestations In early stages Clients may not recognize early symptoms Symptoms progress slowly May not be diagnosed until severe episode with a cold or flu Productive cough Especially in the morning Typically referred to as “cigarette cough” Bronchospasm Frequent respiratory infections

Chronic Bronchitis: Clinical Manifestations Advanced stages Dyspnea on exertion Dyspnea at rest Hypoxemia & hypercapnea Polycythemia Cyanosis Bluish-red skin color Pulmonary hypertension Cor pulmonale

Goals of Treatment: Chronic Bronchitis Improved ventilation Remove secretions Prevent complications Slow progression of signs & symptoms Promote patient comfort and participation in treatment

BRONCHIOLITIS Its an acute viral infection of lower respiratory tract infection affecting nearly 50% of children during 1st year of life and 100% by age of 3 years. Respiratory syncytial virus is the most common cause of bronchiolitis accounting for 70 % of cases.

INFLUENZA Influenza is an acute, viral respiratory infection. Fever, chills, headache, aches and pains throughout the body, sore throat which may lead to bronchitis or pneumonia.

SYMPTOMS FEVER HEADACHE MYALGIA COUGH RHINITIS OCULAR SYMPTOMS

NON-PULMONARY COMPLICATIONS myositis (rare, > in children, > with type B) cardiac complications recent studies report encephalopathy studies of patients <21 yrs in Michigan - 8 cases seen last season liver and CNS Reye syndrome peripheral nervous system Guillian-Barré syndrome

Influenza virus The flu virus is an RNA virus The genome codes for five viral proteins and is made of eight fragments. The virus has a lipid envelope with two glycoproteins present

Symptoms & Diagnosis: Chills Body aches, especially throat and joints Coughing and sneezing Extreme fever Fatigue, headache, and nasal congestion Though similar symptoms occur with a cold, they are much more severe with the flu!

Pharmacotherapy of influenza Although four antiviral agents are commercially available, only two of these have clinical use for treatment of influenza disease in infants and children — oseltamivir (Tamiflu) and zanamivir (Relenza). Oseltamivir is labeled for the treatment and prophylaxis of influenza for those aged 1 year and older. This medication is available as an oral capsule (30 mg, 45 mg, 75 mg) and as an oral suspension (12 mg/mL). Zanamivir is available as an oral inhalation disk and is labeled for use in ages 7 years for treatment and for ages 5 years for prophylaxis. Zanamivir should not be used for children with underlying airway disease, including asthma, due to increased risk for serious bronchospasm.

PNEUMONIA DEFINITION: Acute infection of the lung varying in severity and causing fluid accumulation.  Pneumonia may occur in people of all ages, although young children, the elderly, and immuno compromised patients are especially at risk. Antimicrobial drugs are often used to treat pneumonia.

Types of pneumonia The main classification between the point of infection: community-acquired and hospital pneumonia.  Community-acquired pneumonias are pneumonias in a patient who is not or has not recently been hospitalized. In hospital-acquired pneumonias (or nosocomial pneumonias). Some people catch pneumonia during a hospital stay for another illness. HAP tends to be more serious than CAP because you're already sick. Also, hospitals tend to have more germs that are resistant to antibiotics (medicines used to treat pneumonia).

Community-acquired pneumonia Epidemiology Community-acquired pneumonia (CAP) is a serious illness. It is the fourth most common cause of death in the UK, and sixth in the USA. 85% of cases of CAP are caused by the typical bacterial pathogens, namely, Streptococcus pneumoniae,Haemophilus influenzae, and Moraxella catarrhalis.  The remaining 15% are caused by atypical pathogens, namely Mycoplasma pneumoniae, Chlamydia pneumoniae, andLegionella species. Unusual aerobic gram-negative bacilli (for example, Pseudomonas aeruginosa, Acinetobacter, Enterobacter) rarely cause CAP.

Clinical features They may include headache, malaise, diarrhea, confusion, falling, and decreased appetite. Typical symptoms include cough, purulent sputum production, shortness of breath, pleuritic chest pain, fevers and chills

Hospital-acquired pneumonia Hospital-acquired pneumonia, also called nosocomial pneumonia, is a lung infection acquired after hospitalization for another illness or procedure.  Hospitalized patients have a variety of risk factors for pneumonia, including mechanical ventilation, prolonged malnutrition, underlying cardiac and pulmonary diseases, achlorhydria and immune disorders. These pathogens include resistant aerobic gram-negative rods, such as Pseudomonas , Enterobacter and Serratia, resistant g Antibiotics used for hospital-acquired pneumonia include aminoglycosides, fluoroquinolones, carbapenems, and vancomycin.ram positive cocci, such as MRSA. 

Pathogenesis Inhalation, aspiration and hematogenous spread are the 3 main mechanisms by which bacteria reaches the lungs Primary inhalation: when organisms bypass normal respiratory defense mechanisms or when the Pt inhales aerobic GN organisms that colonize the upper respiratory tract or respiratory support equipment.

Aspiration Pneumonia This type of pneumonia can occur if you inhale food, drink, vomit, or saliva from your mouth into your lungs. This may happen if something disturbs your normal gag reflex, such as a brain injury, swallowing problem, or excessive use of alcohol or drugs. Aspiration pneumonia can cause pus to form in a cavity in the lung. When this happens, it's called a lung abscess (AB-ses)

Atypical Pneumonia Several types of bacteria—Legionella pneumophila, mycoplasma pneumonia, and Chlamydophila pneumoniae—cause atypical pneumonia, a type of CAP. Atypical pneumonia is passed from person to person

TYPES OF ATYPICAL PNEUMONIA Legionella pneumophila. This type of pneumonia sometimes is called Legionnaire's disease, and it has caused serious outbreaks. Mycoplasma pneumonia. This is a common type of pneumonia that usually affects people younger than 40 years old. It may be associated with a skin rash and hemolysis (the breakdown of red blood cells). Chlamydophila pneumoniae. This type of pneumonia can occur all year and often is mild. The infection is most common in people 65 to 79 years old.

A lobar pneumonia is an infection that involves, and is limited to, a single lobe of a lung (generally due to Streptococcus pneumoniae). In contrast, multilobar pneumonia involves more than one lobe. Ventilator-associated pneumonia can be considered a subset of hospital-acquired pneumonia; and in hospitalized or recently discharged patients . Pneumococcal pneumonia is due to S. pneumoniae (around half of all pneumonias). Finally, atypical pneumonia is due to either  Mycoplasma, Chlamydia,or Legionella.

Pathophysiologic process and manifestations. Organisms may enter the respiratory tract through inspiration or aspiration of oral secretions; staphylococcus and Gram-negative bacilli may reach the lungs through circulation in the bloodstream. Normal pulmonary defense mechanisms (cough reflex, mucocilliary transport, and pulmonary macrophages) usually protect against infection.

pathogenesis The invading organism multiplies and releases damaging toxins, causing inflammation and edema of the lung parenchyma; this results in accumulation of cellular debris and exudates. Lung tissue fills with exudates and fluid, In viral pneumonia, the ciliated epithelial cells become damaged. Severity of symptoms depends on the extent of pneumonia present (e.g., partial lobe, full lobe [lobar pneumonia], or diffuse [broncho pneumonia]).

Streptococcus pneumonia Most common cause of CAP Gram positive diplococci “Typical” symptoms (e.g. malaise, shaking chills, fever, rusty sputum, pleuritic hest pain, cough) Lobar infiltrate on CXR Suppressed host 25% bacteremic Predisposing factors: anorexia, ETOH, HIV, sickle cell disease, splenectomy, hematologic diseases

Viral Pneumonia More common cause in children RSV, influenza, parainfluenza Influenza most important viral cause in adults, especially during winter months Post-influenza pneumonia (secondary bacterial infection) S. pneumo, Staph aureus

Other bacteria Anaerobes Aspiration-prone Pt, putrid sputum, dental disease Gram negative Klebsiella - alcoholics Branhamella catarrhalis - sinus disease, otitis, COPD H. influenza Staphylococcus aureus IVDU, skin disease, foreign bodies (catheters, prosthetic joints) prior viral pneumonia

Signs and Symptoms Fever or hypothermia Cough with or without sputum, hemoptysis Pleuritic chest pain Myalgia, malaise, fatigue GI symptoms Dyspnea Rales, rhonchi, wheezing Egophony, bronchial breath sounds Dullness to percussion Atypical Sx’s in older patients

IDSA: Outpt Management in Pt with comorbidities Comorbidities: cardiopulmonary dz or immunocompromised state Organisms: S. pneumo, viral, H. flu, aerobic GN rods, S. aureus Recommended Abx: Respiratory quinolone, OR advanced macrolide Recent Abx: Respiratory quinolone OR Advanced macrolide + beta-lactam

IDSA: Inpt Management: Severe/ICU No risk for Pseudomonas IV beta-lactam plus either IV macrolide, OR IV fluoroquinolone Risk for Pseudomonas Double therapy: selected IV antipseudomonal beta-lactam (cefepine, imipenem, meropenem, piperacillin/tazobactam), plus IV antipseudomonal quinolone -OR- Triple therapy: selected IV antipseudomonal beta-lactam plus IV aminoglycoside plus either IV macrolide, OR IV antipseudomonal quinolone

Switch to Oral Therapy Four criteria: Improvement in cough and dyspnea Afebrile on two occasions 8 h apart WBC decreasing Functioning GI tract with adequate oral intake If overall clinical picture is otherwise favorable, can can switch to oral therapy while still febrile.

Prevention Smoking cessation Vaccination per ACIP recommendations Influenza Inactivated vaccine for people >50 yo, those at risk for influenza complications, household contacts of high-risk persons and healthcare workers Intranasal live, attenuated vaccine: 5-49yo without chronic underlying dz Pneumococcal Immunocompetent ≥ 65 yo, chronic illness and immunocompromised ≤ 64 yo Vaccination may be done either at hospital discharge or during outpatient treatment ACIP: Advisory Committee on Immunization Practices

Pharmacological therapy for lower respiratory tract infections ASPIRIN: ORAL ADULTS: PO 325 to 650 mg prn q 4 to 6 hr or 1 g 3 to 4 times/day. Do not exceed 4 g/day. CHILDREN: PO 10 to 15 mg/kg dose prn q 4 to 6 hr; do not exceed 5 doses/24 hr. Interactions Ethanol: Chronic excessive use may increase risk of hepatotoxicity. Hydantoins, sulfinpyrazone: May decrease therapeutic effect of APAP; concomitant long-term use may increase risk of hepatotoxicity. Adverse Reactions HEMA: Hemolytic anemia; neutropenia; leukopenia; pancytopenia; thrombocytopenia. HEPA: Jaundice. OTHER: Hypoglycemia; allergic skin eruptions or fever.

AMOXICILLIN Capsules: 250 mg (as trihydrate), 500 mg (as trihydrate) Class: Antibiotic/Penicillin Action Inhibits bacterial cell wall mucopeptide synthesis. Clavulanic acid inactivates a wide range of beta-lactam enzymes found in bacteria resistant to penicillins and cephalosporins. Contraindications Hypersensitivity to penicillins, cephalosporins, or imipenem. Not used to treat severe pneumonia,pericarditis, meningitis, and purulent or septic arthritis during acute stage. Lower Respiratory Tract Infections ADULTS AND CHILDREN WEIGHING AT LEAST 40 KG: PO 875 mg q 12 hr or 500 mg q 8 hr. CHILDREN (OLDER THAN 3 MO AND WEIGHING LESS THAN 40 KG): PO 45 mg/kg/day in divided doses q 12 hr or 40 mg/kg/day in divided doses q 8 hr. Adverse Reactions: CNS: Dizziness; fatigue; insomnia; GI: Gastritis; anorexia; nausea; vomiting;HEPA: Transient hepatitis; cholestatic jaundice;GU: Interstitial nephritis

TRIMETHOPRIM-SULFAMETHOXAZOLE(COTRIMOXAZOLE) Action Sulfamethoxazole (SMZ) inhibits bacterial synthesis of dihydrofolic acid by competing with PABA. Trimethoprim (TMP) blocks production of tetrahydrofolic acid by inhibiting the enzyme dihydrofolate reductase. This combination blocks two consecutive steps in bacterial biosynthesis of essential nucleic . Pneumocystis Carinii Pneumonitis ADULTS: PO 20 mg/kg TMP/100 mg/kg SMZ daily in divided doses q 6 hr for 14 days. IV 15–20 mg/kg/day (based on TMP) in 3–4 divided doses for up to 14 days. Exacerbation of Chronic Bronchitis ADULTS: PO 160 mg TMP/800 mg SMZ q 12 hr for 14 days. acids and proteins and is usually bactericidal. Adverse Reactions;CNS: Headache; depression; seizures;GI: Nausea; vomiting; anorexia; abdominal pain; diarrhea;Stevens-Johnson syndrome