Pneumonia Lecture Notes PDF - Pharmacology & Pharmacy Practice

Pneumonia Integrated Sequence VII – PHIDD 1607 Dr. Denise Kolanczyk, PharmD, BCPS Associate Professor, Pharmacy Practice Winter 2024 - 2025 Contact Information Office Phone: 630-515-62...

Pneumonia Integrated Sequence VII – PHIDD 1607 Dr. Denise Kolanczyk, PharmD, BCPS Associate Professor, Pharmacy Practice Winter 2024 - 2025 Contact Information Office Phone: 630-515-6204 Office: Alumni Hall – 391 Email: [email protected] Resources Readings Zasowski EJ, Blackford M. Lower Respiratory Tract Infections. In: DiPiro JT, Yee GC, Haines ST, Nolin TD, Ellingrod VL, Posey L. eds. DiPiro’s Pharmacotherapy: A Pathophysiologic Approach, 12th Edition. McGraw Hill; 2023. Accessed January 14, 2025. https://accesspharmacy.mhmedical.com/content.aspx?bookid=3097&sectionid=26 8014982 Guidelines 1. Metlay JP, Waterer GW, Long AC, et al. Diagnosis and treatment of adults with community-acquired pneumonia: an official clinical practice guideline of the American Thoracic Society and Infectious Diseases Society of America. American Journal of Respiratory and Critical Care Medicine. 2019;200(7):e45-e67. 2. Kalil AC, Metersky ML, Klompas M, et al. Management of adults with hospital-acquired and ventilator-associated pneumonia: 2016 clinical practice guidelines by the Infectious Disease Society of America and the American Thoracic Society. CID. 2016;1-51. Learning Objectives 1. Describe the typical signs and symptoms of pneumonia. 2. Identify between CAP, HAP, VAP, and aspiration pneumonia in terms of definition, risk factors, and common causative organisms. 3. Differentiate between empiric outpatient and inpatient antibiotic treatment strategies for community-acquired pneumonia. 4. Examine all risk factors related to antimicrobial resistance (multi-drug resistant pathogens) that are needed to provide empiric antibiotic recommendations in a patient diagnosed with hospital-acquired pneumonia or ventilator-associated pneumonia. 5. Determine appropriate empiric coverage for bacterial pneumonia (CAP, HAP, or VAP) as well as targeted therapy when culture results are available when given a patient case. 6. Recall dosing regimens for the following antibiotics used in pneumonia: amoxicillin +/- clavulanate, azithromycin, ceftriaxone, doxycycline, levofloxacin, moxifloxacin 7. Recognize appropriate parameters for switching a patient to oral therapy. 8. Identify appropriate durations of therapy for pneumonias. 9. Describe appropriate strategies for prevention of bacterial pneumonia. Pneumonia Page 1 of 15 DEFINITIONS Pneumonia (PNA): lung infiltrate plus clinical evidence that the infiltrate is of infectious origin which include the new onset of fever, purulent sputum, leukocytosis, and decline in oxygenation Community-acquired pneumonia (CAP): pneumonia developing outside the hospital or < 48 hours after hospital admission _______________________________(HAP): pneumonia with onset of > 48 hours after admission in non-ventilated patients _______________________________(VAP): pneumonia that develops in patients who have been mechanically ventilated (i.e., endotracheal intubation) for > 48 hours Aspiration pneumonia: pneumonia caused by aspiration of oropharyngeal or gastrointestinal contents PATHOGENESIS Pneumonia occurs throughout all seasons (all year) Microorganisms gain access to the lower respiratory tract by three routes o Inhalation o Hematogenous o Aspiration Viral lung infections may predispose patients to secondary bacterial pneumonia (suppress antibacterial activity of lung by impairing alveolar macrophage function and mucociliary clearance) ETIOLOGY: the “bugs” Community Acquired Pneumonia Common bacterial pathogens Less common bacterial pathogens o Streptococcus pneumoniae o Staphylococcus aureus o Haemophilus influenza o Escherichia coli o Mycoplasma pneumoniae o Klebsiella pneumoniae o Legionella species o M. tuberculosis o Chlamydia pneumoniae o Fungal Side note: The causative pathogen of CAP in adult patients is most commonly viral. Pneumonia Page 2 of 15 Hospital-Acquired and Ventilator-Associated Pneumonias Pseudomonas aeruginosa Klebsiella pneumoniae Acinetobacter baumanii Escherichia coli Staphylococcus aureus Enterobacter species Aspiration Pneumonia: bacteriology similar to CAP or HAP DIAGNOSIS __________________________________ o Recommended in all adult patients with suspected pneumonia o Routine follow-up of chest imaging for pneumonia is not recommended CLINICAL PRESENTATION SIGNS AND SYMPTOMS PHYSICAL EXAMINATION FINDINGS Abrupt onset of fever, chills Tachypnea and tachycardia Dyspnea Chest wall retractions, grunting respirations Productive cough Dullness to percussion Sputum production +/- hemoptysis Diminished breath sounds Pleuritic chest pain Inspiratory crackles during lung expansion Increased tactile fremitus, whisper pectoriloquy, or egophony CULTURES AND LABORATORY DATA Recommended Cultures Blood cultures Rapid diagnostic tests for viruses Respiratory tract cultures o Not routinely recommended when treating outpatient CAP o Recommend obtaining before starting treatment in hospitalized patients with severe CAP, HAP, or VAP Urinary antigen tests for S. pneumonia and L. pneumophila o Not routinely obtained o Recommended to obtain if patients meet severe CAP criteria Pneumonia Page 3 of 15  Laboratory Tests Complete blood count (CBC) → _______________ usually present Low oxygen saturation on arterial blood gas or pulse oximetry Serum procalcitonin o 2019 IDSA/ATS Guideline: not recommended to determine initial need for antibiotic therapy o May be utilized in practice as an adjunct to clinical judgment for guiding antibiotic therapy decisions GOALS OF THERAPY Eradicate offending organism through selection of appropriate antibiotic(s) Achieve complete clinical cure Minimize adverse drug effects and toxicity Minimize morbidity and mortality Select cost-effective antimicrobials COMMUNITY-ACQUIRED PNEUMONIA (CAP) Risk Factors for the Development of CAP Increasing age Asplenia Diabetes mellitus Chronic cardiovascular, pulmonary, kidney and/or liver disease Smoking and/or alcohol abuse Site of Care Decision: To Admit or Not to Admit? Pneumonia Severity Index (PSI) o Preferred Clinical Prediction Rule for Prognosis (ATS/IDSA 2019 Guidelines) Demographics Co-Morbidities Physical Exam/ Vitals Laboratory/ Imaging Age (1 point per year) Neoplasia +30 Altered mental status +20 Arterial pH < 7.35 +30 - Male Yr Liver disease +20 Respiratory rate ≥ 30/min +20 BUN ≥ 30 mg/dL +20 - Female Yr -10 Heart failure +10 SBP < 90 mmHg +20 Sodium < 130 mmol/L +20 Nursing Home Resident: + 10 CVA +10 Temperature < 35 °C or ≥ 40 Glucose ≥ 250 mg/dL +10 °C +15 Kidney disease +10 Hematocrit < 30% +10 Pulse ≥ 125 bpm +10 Oxygen saturation < 90% (or pulse oximetry < 60 mmHg) + 10 Pleural effusion +10 Pneumonia Page 4 of 15  PSI Score Risk Class Mortality Risk (%) Recommended Site of Care 130 V – high 27% Inpatient Criteria for Severe CAP Major criteria: 1 or more defines severe CAP o Septic shock requiring vasopressors o Respiratory failure requiring mechanical ventilation Minor criteria: 3 or more defines severe CAP o Respiratory rate ≥ 30 o WBC < 4000 cells/mm3 breaths/min o Platelets < 100,000 cells/mm3 o PaO2/FiO2 ratio ≤ 250 o Hypothermia (core temperature o Multilobar infiltrates < 36 °C) o Confusion/disorientation o Hypotension requiring o Uremia (BUN ≥ 20 mg/dL) aggressive fluid resuscitation Let’s get this straight: Respiratory versus Non-Respiratory Fluoroquinolones (FQs) All FQs can penetrate the lungs and maintain adequate concentrations “Respiratory” FQs (levofloxacin, moxifloxacin) implies good coverage towards Streptococcus pneumoniae, whereas “non-respiratory” FQs such as ciprofloxacin has poor coverage towards Streptococcus pneumoniae. EMPIRIC OUTPATIENT CAP STANDARD REGIMENS Criteria Antibiotic Options Previously healthy Amoxicillin 1 gm TID - No antibiotics or hospitalizations within OR last 90 days Doxycycline 100 mg BID - No prior history of respiratory isolation OR of MRSA or Pseudomonas aeruginosa Macrolidea – IF local pneumococcal resistance < 25% Comorbidities (chronic heart, lung, liver, or Respiratory fluoroquinoloneb kidney disease; DM; alcoholism; malignancy; asplenia) OR Immunocompromised or use of β-lactam + macrolidea immunosuppressants - Preferred β-lactam: high dose amoxicillin/clavulanatec OR cephalosporind - Alternative to macrolide: doxycyclinee a - Azithromycin (500 mg on day 1, then 250 mg on days 2-5) or clarithromycin (500 mg BID or ER 1000 mg daily) b - Levofloxacin (750mg daily), moxifloxacin (400 mg daily), delafloxacin (450 mg BID) c - High dose regimens include: 500mg/125mg TID OR 875mg/125mg BID OR 2000mg/125mg BID d - Cefpodoxime 200 mg BID or cefuroxime 500 mg BID e - Consider if QTc prolongation present: doxycycline 100 mg PO BID Pneumonia Page 5 of 15  EMPIRIC INPATIENT CAP STANDARD REGIMENS Criteria Antibiotic Options Nonsevere CAP – no risk β-lactama + macrolideb factors for MRSA or OR Pseudomonas aeruginosa Respiratory fluoroquinolonec Severe CAP – no risk factors for Preferred Regimen: β-lactama + macrolideb MRSA or Pseudomonas aeruginosa Alternate Regimen: β-lactama + respiratory fluoroquinolonec If macrolides and fluoroquinolones are contraindicated: β-lactama + doxycycline a - Ampicillin/sulbactam, cefotaxime, ceftriaxone (1-2 gm IV daily), or ceftaroline b - Azithromycin (500 mg daily) or clarithromycin (500 mg BID) c - Levofloxacin (750 mg IV/PO daily), moxifloxacin (400 mg IV/PO daily), delafloxacin (300 mg IV q12; 450 mg PO q12) Treatment Strategies for Inpatients with CAP and Risk for Drug Resistance Inpatient MRSA Risk Factorsc P. aeruginosa Prior Prior CAP Risk Factorsc Respiratory Respiratory Severity Isolate of Isolate of P. MRSA aeruginosa Obtain cultures +/- Obtain culture Nonsevere nasal PCR Add P. aeruginosa inpatient Add MRSA coverage if culture Add CAP coveragea if culture returns positive MRSA Add P. a or nasal PCR returns coverage aeruginosa positive coverageb Add MRSA Add P. aeruginosa Obtain coveragea and de- coverage and de- cultures Obtain Severe escalate or continue escalate or continue and nasal cultures inpatient therapy based on therapy based on PCR CAP culture and/or nasal culture PCR a – Preferred MRSA coverage: vancomycin or linezolid b – Preferred P. aeruginosa coverage: piperacillin/tazobactam, cefepime, ceftazidime, imipenem- cilastatin, or meropenem; if PCN allergy present, select aztreonam c- Risk factors include hospitalization AND IV antibiotic exposure within 90 days Pneumonia Page 6 of 15 HOSPITAL-ACQUIRED PNEUMONIA (HAP) Lungs are one of the most frequent site of infection acquired in the hospital HAP has a higher mortality rate than any other hospital-acquired (nosocomial) infection Length of stay increased by 7 to 9 days in patients with HAP Serious complications occur in 50% of patients o Respiratory failure, pleural effusions, septic shock, renal failure, empyema Risk Factors for Development of HAP Age > 60 years Medications: antacids, H2 blockers, Witnessed aspiration PPIs COPD, acute respiratory distress Reintubation, tracheostomy, or syndrome (ARDS) patient transport Coma Head trauma, ICP monitoring Supine patient position MDR risk if IV antibiotic use within Enteral feeding, nasogastric tubes 90 days When HAP is Suspected/Diagnosed Presence of new infiltrate on CXR Fever Worsening respiratory status Thick, neutrophil-laden respiratory secretions Approaching Empiric Management of HAP All empiric antibiotic regimens should cover MSSA, Pseudomonas aeruginosa, and other gram-negative bacilli Need to assess if risk factors are present for MDR gram-negative bacilli (including MDR Pseudomonas) and MRSA Risk Factors for Multidrug-Resistant (MDR) Pathogens in HAP Risk Factors for MDR Gram-Negative Bacilli (including MDR Pseudomonas) Prior intravenous antibiotic use within 90 days Structural lung disease (i.e., bronchiectasis, cystic fibrosis) High risk for mortality** Risk Factors for MRSA Prior intravenous antibiotic use within 90 days Hospitalization in unit where >20% of S. aureus isolates are methicillin resistant* Prevalence of MRSA not known in hospital unit* High risk for mortality** *Review institution’s antibiogram for unit-specific isolate rates **High risk for mortality: need for ventilator support due to pneumonia; septic shock Pneumonia Page 7 of 15  EMPIRIC ANTIBIOTIC THERAPY FOR HAP Criteria Options for Antibiotic Regimens No Risk Factors Present Choose one of the following: Piperacillin-tazobactam, cefepime, imipenem-cilastatin, meropenem, OR levofloxacin Risk Factors Present for Choose ONE β-lactam-Based Agent and ONE Non-β-lactam-Based Agent MDR Gram-Negative Bacilli β-lactam-Based Agents Non-β-lactam-Based Agents Piperacillin-tazobactam Levofloxacin OR ciprofloxacin Cefepime OR ceftazidime Tobramycin Imipenem-cilastatin OR meropenem If there are ANY risk factors present for MRSA, ADD vancomycin OR linezolid. If patient has severe PCN allergy and aztreonam is to be used, include coverage for MSSA See APPENDIX A for HAP treatment pathway when approaching empiric antibiotic therapy. VENTILATOR-ASSOCIATED PNEUMONIA Risk for developing VAP increases by 6 to 21 times after a patient is intubated All-cause mortality: 20-50% Prolongation of mechanical ventilation by 7-11 days and hospital stay by 11-13 days Pathophysiology of VAP Bypassing the natural airway defenses against migration of upper respiratory tract organisms into the lower tract o May be exacerbated by acid-reducing drugs (H2 blockers, PPIs) o Increasing pH of gastric secretions may promote proliferation of microorganisms in the upper GI tract o Subclinical microaspirations occur routinely in intubated patients → results in inoculation of bacteria-contaminated gastric contents into lung Risk Factors for the Development of VAP Risk factors: Same as HAP PLUS: o Septic shock o ARDS preceding VAP o Acute renal replacement therapy preceding VAP o 5+ days of hospitalization preceding VAP Pneumonia Page 8 of 15  When VAP is Suspected/Diagnosed No gold standard method exists Should suspect VAP when: o New or persistent infiltrates found on CXR PLUS ≥ 2 of the following: ▪ Purulent tracheal secretions ▪ Leukocytosis or leucopenia ▪ Body temperature > 38.3 Approaching Empiric Management of VAP All empiric antibiotic regimens should cover S. aureus, Pseudomonas aeruginosa, and other gram-negative bacilli Need to assess if risk factors are present for MDR gram-negative bacilli (including MDR Pseudomonas) and MRSA Risk Factors for Multidrug-Resistant (MDR) Pathogens in VAP Risk Factors for MDR Gram-Negative Bacilli (including MDR Pseudomonas) Prior intravenous antibiotic use within 90 days Septic shock at time of VAP ARDS preceding VAP ≥ 5 days of hospitalization prior to occurrence of VAP Acute renal replacement therapy prior to VAP onset Hospitalization in unit where >10% of gram-negative isolates are resistant Antimicrobial susceptibilities for gram-negative isolates not available/unknown Structural lung disease (ie, bronchiectasis, cystic fibrosis) Risk Factors for MRSA Prior intravenous antibiotic use within 90 days Hospitalization in unit where >10-20% of S. aureus isolates are methicillin resistant* Prevalence of MRSA not known in hospital unit* EMPIRIC ANTIBIOTIC THERAPY FOR VAP No Risk Factors Present Choose one of the following: Piperacillin-tazobactam, cefepime, imipenem-cilastatin, meropenem, or levofloxacin Risk Factors Present for Choose ONE β-lactam-Based Agent and ONE Non-β-lactam-Based Agent MDR Gram-Negative Bacilli β-lactam-Based Agents Non-β-lactam-Based Agents Piperacillin-tazobactam Levofloxacin OR ciprofloxacin Cefepime OR ceftazidime Tobramycin Imipenem-cilastatin OR meropenem Colistin OR polymyxin B Aztreonam If there are ANY risk factors present for MRSA, ADD vancomycin OR linezolid. If patient has severe PCN allergy and aztreonam is to be used, include coverage for MSSA. See APPENDIX B for VAP treatment pathway when approaching empiric antibiotic therapy. Pneumonia Page 9 of 15 DIRECTED THERAPY AND NON-RESPONDERS Antibiotic therapy should be de-escalated when possible If applicable: Empiric antibiotics should be modified once culture results are available o De-escalation or narrowing coverage of anticipated organism such as Pseudomonas aeruginosa or Acinetobacter species was not isolated o Modification may be necessary if organism is resistant to antibiotic o Unsuspected pathogen that results may also not be covered by empiric regimen If organism is not known, the oral regimen should be equivalent to the IV regimen that the patient is being transitioned from Some patients may further deteriorate or fail to improve for various reasons such as the wrong organism was empirically covered, a wrong diagnosis, or a complication related to treatment or the pneumonia itself FACTORS TO CONSIDER WHEN TRANSITIONING TO ORAL ANTIBIOTIC THERAPY Bioavailability of agent Functioning GI tract, adequate PO intake Switch from IV to oral therapy when clinical stability is achieved: o Temperature ≤ 37.8 o Heart rate ≤ 100 beats/min o Respiratory rate ≤ 24 breaths/min o Systolic blood pressure ≥ 90 mmHg o Oxygen saturation ≥ 90% or pulse oximetry ≥ 60 mmHg on room air o Ability to maintain oral intake o Normal mental status DURATION OF THERAPY CAP Minimum 5-day course is recommended o Should be afebrile for 48-72 hours before discontinuation of therapy o No more than one sign of clinical instability (see above when switching IV → PO) If CAP was due to suspected or proven MRSA or Pseudomonas aeruginosa, recommended duration of therapy is 7 days HAP/VAP 7-day course of antimicrobial therapy is recommended o Studies have shown no difference in mortality, recurrent pneumonia, treatment failure, hospital length of stay, or duration of mechanical ventilation when compared to long courses of antibiotics (i.e, 10-15 days) o Short antibiotic courses reduce antibiotic exposure, recurrent pneumonia due to MDR organisms, antibiotic-related side effects, C. difficile colitis, and cost Pneumonia Page 10 of 15  PREVENTION Available vaccines for the two leading bacterial causes of pneumonia: Vaccine Brand Name Abbreviation Haemophilus b conjugate vaccine Pneumococcal conjugate vaccine (15-valent) Pneumococcal conjugate vaccine (20-valent) Pneumococcal conjugate vaccine (21-valent) Pneumococcal polysaccharide vaccine (23-valent) Adult Recommendations for the Pneumococcal Vaccine Immunization Status Administration Recommendations Adults ≥ 50 years 1 dose PCV20 or 1 dose PCV21 Pneumococcal vaccine-naive OR OR vaccination status unknown 1 dose PCV15 followed by PPSV23 ≥1 year later Adults Aged 19-49 1 dose PCV20 or 1 dose PCV21 With certain underlying medical OR conditions or 1 dose PCV15 followed by PPSV23 ≥1 year later immunocompromising conditions In adults with immunocompromising conditions(*see list below), cochlear (refer to lists below) implant, or CSF leak, a minimum interval of ≥ 8 weeks can be considered **Special note: If patients previously received PCV7, PCV13 and/or PPSV23, refer to the current Adult Immunization Schedule for recommendations on how to proceed. *Immunocompromising Conditions Underlying Medical Conditions Chronic kidney failure Alcoholism Congenital or acquired asplenia Chronic heart disease (includes HF and cardiomyopathies) Generalized malignancy Chronic kidney failure HIV infection Chronic liver disease Hodgkin disease Chronic lung disease (includes COPD, emphysema, and asthma) Iatrogenic immunosuppression Cigarette smoking Immunodeficiencies Cochlear implant Leukemia Congenital or acquired asplenia Lymphoma CSF leak Multiple myeloma Diabetes mellitus Nephrotic syndrome Generalized malignancy Sickle cell disease or other HIV infection hemoglobinopathies Hodgkin disease Solid organ transplant Iatrogenic immunosuppression Immunodeficiencies Leukemia Lymphoma Multiple myeloma Nephrotic syndrome Sickle cell disease or other hemoglobinopathies Solid organ transplant Pneumonia Page 11 of 15  Adult Recommendations for the Haemophilus B Vaccine Recommended in adults who did not have the childhood Hib series and at increased risk for invasive Hib disease o Increased risk is defined as: ▪ Anatomic/functional asplenia (including sickle cell disease) ▪ Splenectomy o Dose recommendation: one single dose of either vaccine listed in table Recommended in adults who are recipients of a hematopoietic stem cell transplant o Dose recommendation: 3-dose series 4 weeks apart starting 6-12 months after a successful transplant, regardless of Hib vaccination history Vaccine Recommendations for Adults by Age Pneumonia Page 12 of 15  Vaccine Recommendations for Adults by Health Condition Pneumonia Page 13 of 15  APPENDIX A: Empirical Therapy for Hospital-Acquired Pneumonia Does my patient have a “High Mortality Risk”? No MRSA Risk Factors? Yes Yes Vancomycin or Linezolid PLUS Antipseudomonal B-lactam No PLUS GNR Risk Factors? Antipseudomonal non-B-lactam Yes No Vancomycin or Linezolid Vancomycin or Linezolid PLUS PLUS Antipseudomonal B-lactam Antipseudomonal B-lactam PLUS Antipseudomonal non-B-lactam GNR Risk Factors? Yes No Antipseudomonal B-lactam Antipseudomonal B-lactam PLUS Antipseudomonal non-B-lactam GNR Risk Factors Specific to MDR for gram-negative bacilli only Pneumonia Page 14 of 15  APPENDIX B: Empirical Therapy for Ventilator-Associated Pneumonia Does my patient MDR Risk Factors for Gram Negative Bacilli? No MRSA Risk Factors? Yes Yes Antipseudomonal B-lactam Antipseudomonal B-lactam PLUS PLUS No Antipseudomonal non-B-lactam Vancomycin or Linezolid MRSA Risk Factors? No Yes Antipseudomonal B-lactam PLUS Antipseudomonal non-B-lactam Antipseudomonal B-lactam Vancomycin or Linezolid PLUS Antipseudomonal B-lactam PLUS Antipseudomonal non-B-lactam Pneumonia Page 15 of 15