PNEUMONIA. Patient Case: Chief Complaint: I have been short of breath and have been coughing up rust-colored phlegm for the past 3 days.

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1 PNEUMONIA Relevant Guidelines: 2008 IDSA CAP guidelines: an_system/lower/upper_respiratory/community-acquired_pneumonia_(cap)/ 2016 IDSA HAP/VAP guidelines: an_system/lower/upper_respiratory/hospital-acquired_pneumonia_(hap)/ Learning Objectives: Identify signs and symptoms that may indicate a pneumonia infection List common causative organisms and risk factors for community-acquired and hospital-acquired pneumonias Distinguish between antibacterial treatments for pneumonia in the organisms they cover Describe supportive therapies that may be indicated in treatment of pneumonia Patient Case: Chief Complaint: I have been short of breath and have been coughing up rust-colored phlegm for the past 3 days. HPI: James Thompson is a 55-year-old African-American man with a 3-day history of worsening shortness of breath, subjective fevers, chills, right-sided chest pain, and a productive cough. The patient states that his initial symptom of shortness of breath began approximately 1 week ago after delivering mail on an extremely cold winter day. After several days of not feeling well, he went to an immediate care clinic and received a prescription for levofloxacin 750 mg orally once daily for 5 days, which he did not fill due to financial reasons. He has been taking acetaminophen and an over-the-counter cough and cold preparation, but feels that his symptoms are getting much worse. The patient began experiencing right-sided pleuritic chest pain and a productive cough with rust-colored sputum over the past 3 days, and feels that he has been feverish with chills, although he did not take his temperature. On presentation to the ED, he is febrile and appears visibly short of breath. PMH: Hypertension 15 years, Type 2 diabetes mellitus 10 years Meds: Prescription Patient states that he only sporadically takes his medications due to financial reasons Lisinopril 10 mg orally once daily Hydrochlorothiazide 25 mg orally once daily Metformin 1000 mg orally twice daily Over-the-Counter Acetaminophen 650 mg orally every 6 hours as needed for pain Guaifenesin /dextromethorphan (100 mg/10 mg/5 ml) two teaspoonfuls every 4 hours as needed for cough

2 Allergies Amoxicillin (rash as a child). Patient has received cephalexin as an adult without problem. SH: Lives with wife and 4 children, employed as mail carrier, denies alcohol, tobacco, illicit Highlight the signs and symptoms that may indicate a case of pneumonia. Think about what you already know about pneumonia and how these case details relate. Background Community-acquired pneumonia (CAP) is defined as an acute infection of the pulmonary parenchyma in a patient who has acquired the infection in the community, as distinguished from hospital-acquired (nosocomial) pneumonia (HAP). HAP (or nosocomial pneumonia) is pneumonia that occurs 48 hours or more after admission and did not appear to be incubating at the time of admission. VAP is defined as pneumonia occurring more than 48 hours post-endotracheal intubation. HCAP (healthcare-associated pneumonia) is pneumonia in patients who have had contact with the healthcare system and may be at risk for MDR organisms. HCAP was not included in the most recent HAP/VAP guidelines because it was determined that risk for MDR should include patient-specific risk factors, not only prior contact with healthcare. Special consideration should be given to patients in long term care facilities, rehabilitation centers, and dialysis centers for their unique risk for pneumonia. Pathophysiology: 3 sites of entry into the body for microorganisms 1) inhaled as aerosolized particles 2) enter the lung via the bloodstream from an extrapulmonary infection site 3) via aspiration of oropharyngeal contents If lung defenses are impaired greater risk of developing pneumonia Signs and Symptoms: Abrupt onset of fever, chills, dyspnea, and productive cough Rust-colored sputum or hemoptysis Pleural effusions (distant breath sounds) Pleuritic chest pain Patient may be hypoxic CBC usually reflects leukocytosis with predominance of polymorphonuclear cells Elevation of WBC count may be pronounced Gen : Patient is a well-developed, well-nourished, African-American man in moderate respiratory distress appearing somewhat anxious and uncomfortable.

3 VS : BP 155/85, P 127, RR 30, T 39.5 C; Wt 110 kg, Ht 5 11 Skin : Warm to the touch; poor skin turgor HEENT : PERRLA; EOMI; dry mucous membranes Neck/Lymph Nodes : No JVD; full range of motion; no neck stiffness; no masses or thyromegaly; no cervical lymphadenopathy Lungs/Thorax : Tachypneic, labored breathing; coarse rhonchi throughout right lung fields; decreased breath sounds in right middle and right lower lung fields CV : Audible S1 and S2; tachycardic with regular rate and rhythm; no MRG Abd : NTND; (+) bowel sounds Genit/Rect : Deferred Extremities : No CCE; 5/5 grip strength; 2+ pulses bilaterally Neuro : A & O 3; CN II XII intact What signs and symptoms of the patient reinforce the initial thought that this may be pneumonia? What other information would you like to have to help you formulate a treatment plan if this is indeed pneumonia? Diagnosis and determination of organisms: Chest radiograph Sputum examination and culture for gram-positive and gram-negative bacterial pneumonia Gram stain shows many polymorphonuclear cells and predominant organism ABG : ph 7.38; PaCO2 29; PaO2 70 make HCO3 25 meq/l with 87% O2 saturation on room air Chest X-Ray : Right middle and right lower lobe consolidative airspace disease, likely pneumonia. Left lung is clear. Heart size is normal. Chest CT Scan Without Contrast : No axillary, mediastinal, or hilar lymphadenopathy. The heart size is normal. There is consolidation of the right lower lobe and lateral segment of the middle lobe, with air bronchograms. No significant pleural effusions. The left lung is clear. Sputum Gram Stain : >25 WBCs/hpf, <10 epithelial cells/hpf, many Gram (+) cocci in pairs Sputum Culture : Pending Blood Cultures Two Sets : Pending Other Lab Tests: Streptococcus pneumoniae urine antigen Pending; Legionella pneumophila urine antigen Pending How can you use this additional information to help guide your treatment plan?

4 Treatment Considerations Determine presence of signs of systemic illness Supportive care Mechanical ventilation and fluid resuscitation in severe cases Humidified oxygen for hypoxemia Bronchodilators when bronchospasm is present Adequate hydration (IV if necessary) Nutritional support Control of fever Antimicrobial agents Empiric use of relatively broad-spectrum antibiotic effective against probable pathogens after cultures have been sent Narrow therapy once results of cultures are known Monitoring Clinical stability classified as: temperature 37.8 C, heart rate 100 beats/min, respiratory rate 24 breaths/min, systolic blood pressure 90 mm Hg, arterial oxygen saturation 90% or po 2 60 mm Hg on room air, ability to maintain oral intake, and normal mental status. What drug, dose, route of therapy, dosing schedule, and duration of treatment should be used in this patient? While in the ED, the patient was placed on 4 L NC of O2, and his oxygen saturation improved to 98%. The patient was initiated on ceftriaxone 1 g IV daily and azithromycin 500 mg IV daily and admitted to the hospital. Over the next 48 hours, the patient s clinical status improved with decreasing fever, tachypnea, tachycardia, and shortness of breath. On hospital day 2, the S. pneumoniae urine antigen was positive, and the sputum culture demonstrated the growth of S. pneumoniae, resistant to erythromycin (MIC 1 mcg/ml), but susceptible to penicillin (MIC 2 mcg/ml), ceftriaxone (MIC 1 mcg/ml), levofloxacin (MIC 0.5 mcg/ml), and vancomycin (MIC 1 mcg/ml). How would this change your therapeutic plan? IDSA CAP Guidelines Most common etiologies of CAP Outpatient Streptococcus pneumoniae, Mycoplasma pneumoniae, Haemophilus influenzae, Chlamydophila pneumoniae, Respiratory viruses Inpatient (non-icu) S. pneumoniae, M. pneumoniae, C. pneumoniae, H. influenzae, Legionella species, aspiration, respiratory viruses Inpatient (ICU) S. pneumoniae, Staphylococcus aureus, Legionella species, gram-negative bacilli, H. influenzae

5 Hospital Admission Decision CURB-65 (severity of illness score) or Pneumonia Severity Index (PSI) can be used to identify patients with CAP who may be candidates for outpatient treatment CURB-65 = confusion, uremia, respiratory rate, low blood pressure, age 65 or greater CURB-65 score of 2 or more usually warrants hospitalization Utilize both objective and subjective factors ICU Admission Decision Required for septic shock requiring vasopressors or acute respiratory failure requiring intubation and mechanical ventilation Recommended for patients with 3 of the minor criteria for severe CAP: Respiratory rate 30 or more breaths/min PaO2/FiO2 ratio less than or equal to 250 Multilobar infiltrates confusion/disorientation Uremia Leukopenia Thrombocytopenia Hypothermia Hypotension requiring fluid resuscitation Antibiotic Treatment Previously healthy, no use of antimicrobials within previous 3 months A macrolide (azithromycin) Alternative: doxycycline Presence of comorbidities such as chronic heart, lung, liver, or renal disease, DM, alcoholism, malignancies, asplenia, immunosuppression, or use of antimicrobials within the previous 3 months A beta lactam plus a macrolide Preferred treatment Alternative: respiratory fluoroquinolone (moxi, gemi, or levo) Inpatients, non-icu treatment A beta lactam plus a macrolide Preferred treatment Alternative: respiratory fluoroquinolone Inpatients, ICU treatment A beta lactam plus either azithromycin or a respiratory fluoroquinolone Pcn allergy: respiratory fluoroquinolone and aztreonam are recommended Special concerns If Pseudomonas is a consideration An antipneumococcal, antipseudomonal beta lactam (piperacillin-tazobactam, cefepime, imipenem, or meropenem) plus either ciprofloxacin or levofloxacin

6 or the above beta lactam plus an aminoglycoside and azithromycin or the above beta lactam plus an aminoglycoside and an antipneumococcal fluoroquinolone (for penicillin-allergic patients, substitute aztreonam for above beta lactam) If CA-MRSA is a consideration, add vancomycin or linezolid Switch to oral therapy: When patient is hemodynamically stable and improving clinically When patient is able to ingest medications If patient has a normally functioning GI tract Duration: Minimum of 5 days; should be afebrile for hours Longer duration warranted if initial therapy not active against identified pathogen or if it was complicated by extrapulmonary infection Dosing Guide Azithromycin 500 mg IV q24h Levofloxacin 750 mg IV q24h Ceftriaxone 1g IV q12h Azithromycin 250 mg PO (Z-pack regimen) x 5 days Cefuroxime 500 mg PO BID Amoxicillin 1 g PO TID

7 IDSA HAP/VAP Guidelines Hospital Acquired Pneumonia (developing >48 hours after hospital admission) Leading causative agents: Gram-negative aerobic bacilli Pseudomonas E. coli Klebsiella pneumoniae S. aureus (MSSA or MRSA) Multidrug resistant (MDR) pathogens

8 Risk factors for MDR pathogens: prior IV antibiotic use within 90 days Additional risk factors for MDR VAP: septic shock at time of VAP ARDS preceding VAP 5 or more days of hospitalization prior to VAP acute renal replacement therapy prior to VAP onset Antibiotic Treatment of HAP Use local antibiogram for treatment selection Coverage of Staph. Aureus Cover for MRSA in patients with either a MRSA risk factor or who have high mortality risk MRSA risk factors: Prior IV antibiotic use within 90 days Unit where >20% of S. aureus isolates are methicillin resistant Unit where prevalence of MRSA is not known High mortality risk factors: septic shock, ventilator support Otherwise, coverage of MSSA suggested Coverage of Pseudomonas and other GNRs Double cover for Pseudomonas if patient has risk factors increasing the likelihood of gram-negative infection or high mortality risk (antibiotics from 2 different classes with Pseudomonas activity) High mortality risk factors: septic shock, ventilator support GNR risk factors: prior IV antibiotic use within 90 days Single coverage recommended for empiric treatment without risk factors Avoid aminoglycosides as the sole antipseudomonal agent Duration: 7 day course of antimicrobial therapy Therapy should be de-escalated from broad narrow coverage when causative organism is known Antibiotic Treatment of VAP Use local antibiogram for treatment selection Coverage for Staph. Aureus Cover MRSA if patients have a risk factor for antimicrobial resistance Unit where >10-20% of S. aureus isolates are methicillin resistant Units where prevalence of MRSA is not known Otherwise, coverage of MSSA recommended Coverage for Pseudomonas and other GNRs Double coverage with antipseudomonal antibiotics from different classes only in patients with: Risk factor for multi-antimicrobial resistance Units where >10% of gram-negative isolates are resistant to an agent being considered for monotherapy Units where local susceptibility rates are not available

9 Otherwise, single coverage of Pseudomonas recommended Avoid aminoglycosides if alternatives are available Avoid colistin if alternatives are available Duration: 7 day course of antimicrobial therapy Therapy should be de-escalated from broad narrow coverage when causative organism is known

10 Other Resources: Link to DiPiro Casebook: Link to DiPiro Chapter 107: estaccesskey=daa5d48f-8a6a-4c6e-85ea-d4ed6088a481