Legionnaire s Disease: Overview and Treatment

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Legionnaire s Disease: Overview and Treatment Sarah Newman, PharmD PGY1 Pharmacy Practice Resident Nicklaus Children s Hospital Disclosures Authors of this presentation have the following to disclose

1 Legionnaire s Disease: Overview and Treatment Sarah Newman, PharmD PGY1 Pharmacy Practice Resident Nicklaus Children s Hospital Disclosures Authors of this presentation have the following to disclose concerning possible financial or personal relationships with commercial entities that may have a direct or indirect interest in the subject matter of this presentation. Sarah Newman: nothing to disclose. Objectives Describe the epidemiological risk factors for Legionnaire s disease. Differentiate between the clinical features of Legionnaire s disease and Pontiac fever. Design an antibiotic regimen for treatment of Legionnaire s disease. 1

2 Quiz Question 1 T/F: A mild infection caused by Legionella bacteria is known as Pontiac fever. Quiz Question 2 T/F: Levofloxacin 750 mg once daily for 10 days is an appropriate antibiotic treatment for Pontiac fever. Quiz Question 3 T/F: Potable water systems, whirlpool spas, and cooling towers are common sources of Legionnaire s disease outbreaks. 2

Philadelphia: 1968 1 Annual convention of the American Legion at the Bellevue-Stratford Hotel 221 attendees contract a mysterious respiratory tract infection 34 patients died The bacteria was finally

Payne, whose fever spiked at 107.4 degrees.

3 Philadelphia: Annual convention of the American Legion at the Bellevue-Stratford Hotel 221 attendees contract a mysterious respiratory tract infection 34 patients died The bacteria was finally isolated six months later by CDC researchers Source of the infection was traced to the hotel s water cooling system Dr. Stephen B. Thacker, a federal epidemiologist, in August 1976 with Thomas A. Payne, whose fever spiked at degrees. (NY Times) July Bronx, NY: Legionnaire s outbreak infects more than 130 patients and kills 16 Traced to cooling tower above the Opera House Hotel Deadliest Legionella outbreak in New York s history October Bronx, NY: new cases of Legionnaire s disease and one death reported New outbreak appears to be unrelated to July outbreak 15 cooling towers in the Morris Park area test positive for Legionella Outbreak traced to cooling tower above Bronx Psychiatric Center 3

Bronx, NY: 2015 4,5 Outbreaks in New York have increased dramatically over the last decade: 73 cases in 2004 vs.

every 90 days Epidemiology 6 8,000 18,000 cases/year in the United States National reported cases tripled between 2001 and 2012 Outbreaks typically occur in the summer and fall Caused by bacteria

4 Bronx, NY: ,5 Outbreaks in New York have increased dramatically over the last decade: 73 cases in 2004 vs. 225 cases in 2014 In August 2015, NY state government enacted legislation related to outbreaks Building owners must register and test water cooling towers within 30 days All towers must be retested every 90 days Epidemiology 6 8,000 18,000 cases/year in the United States National reported cases tripled between 2001 and 2012 Outbreaks typically occur in the summer and fall Caused by bacteria from the Legionella family Most frequent cause of waterborne illness in humans in the United States Legionella Family 6 Gram-negative aerobe At least 50 species Most common human pathogen is Legionella pneumophila Prefer warm, moist environments Outbreaks have been tied to cooling towers, whirlpool spas, decorative fountains, and grocery store misters Most common route of infection is via inhalation of the aerosolized particles pneumonia Human-to-human transmission has not been demonstrated 4

treated for pneumonia who do not respond to beta-lactam and/or aminoglycosides antibiotics Diagnosis 7 Atypical bacteria Typical gram stains will show neutrophils but few, if any, organisms If sputum

5 Signs and Symptoms 7,8 In general, pneumonia symptoms accompanied by: Fever >38.8 o C (temperatures > 40 o C common) Dyspnea Myalgia/arthralgia Diarrhea Nausea/vomiting Neurological abnormalities Chest pain Non-specific lab findings Suspect Legionnaire s disease in patients treated for pneumonia who do not respond to beta-lactam and/or aminoglycosides antibiotics Diagnosis 7 Atypical bacteria Typical gram stains will show neutrophils but few, if any, organisms If sputum culture is obtained, may be plated on black charcoal yeast extract Rapid diagnostic tests Urinary antigen Polymerase chain reaction (PCR) Up to Date Diagnosis 7 Fever precedes any radiographic abnormalities, so diagnosis of pneumonia may be missed during the first 1-3 days of illness Begins with patchy, unilobar infiltrate that progresses to consolidations No characteristic chest x- ray finding Chest

6 Common Pathogens 9 Community Acquired Pneumonia: Streptococcus pneumoniae 20-60% Haemophilus influenzae 3-10% Staphylococcus aureus 3-5% Klebsiella pneumoniae, other GNRs 3-10% Mycoplasma pneumoniae 4-6% Chlamydophilia pneumoniae 4-6% Other bacteria 3-5% Legionella species 2-4% Viruses 2-15% Mortality Associated with Common Pathogens 9 Community Acquired Pneumonia Psuedomonas aeruginosa 61% Klebsiella pneumoniae 36% Staphylococcus aureus 32% Legionella species 15% Streptococcus pneumoniae 12% Chlamydophila pneumoniae 10% Haemophilus influenzae 7% Mycoplasma pneumoniae 1% Pontiac Fever 6 Following identification of Legionella, analysis of stored serum from an earlier unidentified outbreak revealed Legionella was the cause Signs and symptoms Milder course of disease compared to Legionnaire s disease Fever Chills Fatigue Headache No respiratory complaints Usually self-limiting No need to treat with antibiotics 6

7 Clinical Features of Legionellosis 6 Legionnaire s disease Pontiac fever Clinical features Pneumonia, cough fever Flu-like illness without pneumonia Radiographic pneumonia? Yes Incubation period 2-10 days hours No Percent of persons who become ill when exposed to outbreak Less than 5% Greater than 90% Isolation of organism Possible Never possible Outcome Hospitalization common Case fatality rate: 5-30% Hospitalization uncommon Case fatality rate: 0% Reproduced from Patient Risk Factors 6 Legionnaire s disease Recent travel with overnight stay Cigarette smoking Chronic lung disease Solid organ transplant patients Age > 50-years-old Likely associated with increasing comorbidities as patients age Pontiac fever Smoking and patient age do not appear to be risk factors Typically infects younger patients (mean age = 29) Supportive Therapy 10 Antipyretics Acetaminophen Ibuprofen Antitussives Dextromethorphan Codeine Bronchodilators Albuterol Hydration and adequate nutrition Supplemental oxygen 7

8 Pharmacological Therapy 8 Preferred: Levofloxacin 750 mg IV QD, then 750 mg PO x 10 days (high-dose) Moxifloxacin 400 mg IV QD, then 400 mg PO QD x 10 days Azithromycin 1000 mg IV QD on day 1, then 500 mg PO or IV QD x 10 days Alternatives: Ciprofloxacin 500 mg IV BID, then 500 mg PO BID x 10 days Doxycycline 100 mg IV BID, then 100 mg PO BID x 10 days Levofloxacin Fluoroquinolone Pharmacokinetics 11 High-dose maximizes concentration-dependent killing Increases plasma concentrations and penetration into the lungs Prevents development of resistance Ciprofloxacin Not considered a respiratory fluoroquinolone because of inactivity against Streptococcus pneumoniae species In vitro activity against Legionella species BID dosing Fluoroquinolone Plasma Concentrations 11 8

Switching from IV to PO 10 Recommend switching patients from IV to PO antibiotics when they have been afebrile for 48-72 hours and have no more than one of the following signs of clinical

9 Switching from IV to PO 10 Recommend switching patients from IV to PO antibiotics when they have been afebrile for hours and have no more than one of the following signs of clinical instability: Temperature >37.8 o C Tachycardia Tachypnea Hypotension O2 desaturation NPO status Mental status changes from baseline Pediatric Legionella Infection 12 Of the 23,076 cases of Legionnaire s disease reported between 1990 and 2005, only 1.7% of cases were in pediatric patients Adolescents 15-19: 44.3% Infants < 1-year-old: 18.1% Most cases are hospital-acquired Many have been traced to hospital tap water Two cases were reported in infants who were born in warm water during water births Levofloxacin Pediatric Treatment Options 13 6 months and <5 years: IV: 8 to 10 mg/kg/dose every 12 hours; maximum daily dose: 750 mg/day 5 years and 16 years: IV: 8 to 10 mg/kg/dose once every 24 hours; maximum daily dose: 750 mg/day Azithromycin 10 mg/kg IV once daily for at least two days, then transition to oral route with a single daily dose of 5 mg/kg to complete therapy course, max dose = 500 mg/dose Ciprofloxacin Ciprofloxacin mg/kg IV BID, max dose = 800 mg/day 9

Fluoroquinolone Use in Pediatrics 14 Controversies: Increased bacterial resistance Irreversible adverse effects on cartilage development demonstrated in animal models 3.

10 Fluoroquinolone Use in Pediatrics 14 Controversies: Increased bacterial resistance Irreversible adverse effects on cartilage development demonstrated in animal models % absolute risk increase in arthropathies or musculoskeletal events At the time of the September 2011 FDA Pediatric Drugs Advisory Committee, 5 events of tendon rupture had been reported in pediatric patients 112,000 patients had received prescriptions for a FQ during that time period Fluoroquinolone Use in Pediatrics 14 Potential uses: Multi-drug resistant infections Cystic fibrosis CAP caused by atypical pathogens FDA indications: Anthrax: levofloxacin and ciprofloxacin Complicated UTI and pyelonephritis infections: ciprofloxacin Risk vs. benefit Limit FQ use in pediatrics to selected respiratory infections and infections due to MDR organisms Role of the Pharmacist Antimicrobial stewardship: patients presenting with Pontiac fever do not require treatment with antibiotics Pharmacists may be helpful in recommending: Appropriate antibiotic selection High-dose levofloxacin therapy to maximize PK parameters When to switch patients from IV to PO therapy 10

11 Quiz Question 1 T/F: A mild infection caused by Legionella bacteria is known as Pontiac fever. Quiz Question 2 T/F: Levofloxacin 750 mg once daily for 10 days is an appropriate antibiotic treatment for Pontiac fever. Quiz Question 3 T/F: Potable water systems, whirlpool spas, and cooling towers are common sources of Legionnaire s disease outbreaks. 11

12 Any questions? Thank you! Sources 1. Altman LK Aug 1. In Philadelphia 30 Years Ago, an Eruption of Illness and Fear. The New York Times NBC New York August 20. Source of Deadly Legionnaire s Outbreak Identified. Retrieved from Disease-New-York-City-Bronx-Cooling-Tower-Death-Sick-Outbreak-Source-Health- Department html. 3. Mueller B October 1. One Dead in New Bronx Outbreak of Legionnaire s Disease. The New York Times. Retrieved from latedcoverage&region=marginalia&pgtype=article. 4. Press Release August 17. Governor Cuomo Announces Statewide Emergency Regulations to Combat Legionnaire s Disease. Retrieved from Sources 5. Miller HI Aug. CDC s Approach to Legionnaire s Disease Causes Preventable Outbreaks. Forbes. Retrieved from 6. Centers for Disease Control and Prevention. (2015). Legionella Yu VL, et al. Clinical manifestations and diagnosis of Legionella infection. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, Yu VL, et al. Treatment and prevention of Legionella. In: UpToDate, Post, TW (Ed), UpToDate, Waltham, MA, Fine MJ, et al. Prognosis and outcomes of patients with community-acquired pneumonia: a meta-analysis. JAMA Jan 10;275(2):

13 Sources 10. Mandell LA, et al. Infections Diseases Society of American/American Thoracic Society Consensus Guidelines on the Management of Community Acquired Pneumonia in Adults. Clin Infectious Disease. 2007;44(Suppl 2): S27-S Gottfried MH, et al. Steady-state plasma and intrapulmonary concentrations of levofloxacin and ciprofloxacin in healthy adult subjects. Chest April;119(4): Shachor-Meyouhas Y. Legionnaire s disease in children. Retrieved from Lexicomp Online, Pediatric & Neonatal Lexi-Drugs, Hudson, Ohio: Lexi-Comp, Inc.; December 15, Kline JM, et al. Pediatric Antibiotic Use: A Focused Review of Fluoroquinolones and Tetracyclines. US Pharm. 2012;37(8):

THIS IS AN OFFICIAL NH DHHS HEALTH ALERT

THIS IS AN OFFICIAL NH DHHS HEALTH ALERT Distributed by the NH Health Alert Network Health.Alert@nh.gov August 25, 2018 0800 EDT NH-HAN 20180825 Cluster of Legionella pneumophila Pneumonia (Legionnaire