Disclosure. Bugs and Drugs at the Point of Transition. Objectives 3/21/2018. All antibiotic use, even appropriate, drives resistance

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Disclosure Bugs and Drugs at the Point of Transition No financial or other conflicts of interest to disclose. Presenter: Katerina Petrov, Pharm.D., BCPS March 24 th, 2018 Objectives Outline outpatient and inpatient antimicrobial stewardship program objectives to coordinate and promote appropriate prescribing of antibiotics Review bugs and drugs for community acquired pneumonia in the ambulatory and inpatient settings Describe good antimicrobial stewardship practices to promote appropriate antibiotic use at points of transition in patient care Antibiotics are not being optimally used Live saving antibiotics are not working as well Main reason: antibiotic overuse and misuse ~30-50% of antibiotic use is inappropriate In most cases of misuse, no antibiotic is needed 47 million unnecessary prescriptions in US annually Antibiotics responsible for 1 of 5 ED visits due to ADRs Studies show limited improvement over time CDC. Unnecessary antibiotic prescriptions. 2016 4 All antibiotic use, even appropriate, drives resistance The Burden of Antibiotic Resistance CDC. Antibiotic Resistance Threats in the United States, 2013. 5 CDC. Antibiotic Resistance Threats in the United States, 2013. 6 1

Drug Development Outpaced Combating antibiotic resistance CDC suggested core actions: 1. Preventing infections, preventing the spread of resistance 2. Tracking antibiotic resistance infections 3. Improving antibiotic use/stewardship 4. Developing new drugs and diagnostic tests Pew Charitable Trusts. 2016 7 8 White House National Action Plan By 2020 the United States will: Reduce C. difficile infections by 50% What is an Antimicrobial Stewardship Program (ASP)? DEFINITION: Reduce carbapenem-resistant Enterobacteriaceae infections by 60% Reduce multi-resistant Pseudomonas infections by 35% Reduce MRSA bloodstream infections by 50% Reduce invasive pneumococcal infection in adults >65 yo by 25% Reduce inappropriate outpatient antibiotic use by 50% Reduce inappropriate inpatient antibiotic use by 20% https://obamawhitehouse.archives.gov/sites/default/files/docs/national_action_plan_for_combating_antibotic-resistant_bacteria.pdf Coordinated interventions designed to improve and measure the appropriate use of antibiotic agents by promoting the selection of the optimal antibiotic regimen including dosing, duration of therapy, and route of administration. IDSA/SHEA/PIDS 9 Key Policy Developments in Stewardship Goals of Stewardship Programs September 2014: President Obama issues Executive Order to combat antibiotic resistant bacteria March 2015: The National Action Plan to Combat Antibiotic Resistant Bacteria is published June 2016: CMS releases proposed guidelines for antimicrobial stewardship January 2017: TJC began surveying on antimicrobial stewardship standards. November 2017: Stewardship Requirement for nursing homes take effect Improve Patient Outcomes Reduce Antimicrobial Resistance Improve Patient Safety Reduce Antimicrobial Expenditure McGowan JE. Infect Control Hosp Epidemiol. 2012; 33:33:331-337. Dodds Ashley ES, et al. Clin Infect Dis. 2014; 59 (s3): S112-S121 2

Active Passive 3/21/2018 The ASP Team Infectious Disease Physician(s)* Clinical Pharmacist(s) with infectious disease training* Clinical Microbiologist IT Specialist Infection Control Professional Hospital Epidemiologist * IDSA deems these as necessary, and other team members are optional ASP Core Elements Leadership Commitment Accountability Drug Expertise Action Tracking Reporting Education Inpatient ASP Intervention Examples Front End Before Rx Restrictions Order Sets Back End After Rx Audit and real-time feedback IV to PO programs Dose Optimization How do we decrease inappropriate use in the community? Provider Audit reports Educational programs Guidelines Antibiotic prescription Patient disposition Technology-based alerts: Bug-drug mismatch de-escalation Duration of therapy Moehring RW, Anderson DJ. Curr Infect Dis Rep 2012;14:592-600 16 Why focus on outpatient use? Majority of antibiotic use occurs outside of inpatient setting Mismatch of resources, large proportion unnecessary 10% decrease in inappropriate prescribing in community 17% reduction in Clostridium difficile infection Antibiotic expenditure in US, 2009 17 Sudaet et al. J Antimicrob Chemother 2013; 68: 715-8; Dantes et al. Open Forum Infect Dis. 2015; 2(3) Reasons for antibiotic misuse in the community Provider- or patient-related Diagnostic uncertainty Patient demands or expectations Misdiagnosis of nonbacterial infection Concerns of litigation Knowledge deficit, or failure to utilize knowledge Inadequate time to explain that antibiotics are not needed Fleming-Dutra K et al. JAMA. 2016; 315(17): 1864-73 18 3

Challenges in Outpatient ASP Most common indications for abx Multiple providers Less frequent follow up Limited Information Antimicrobial Delivery Patient Expectations Limited Resources National survey database of ambulatory care providers utilized to characterize prescribing patterns (2010-2011) 12.6% (n= 23,740) of all ambulatory visits resulted in antibiotic Rx Diagnosis Visits with antibiotics prescribed, % (95% CI) Sinusitis 56 (48 64) Otitis media 47 (41 54) Pharyngitis 43 (38 43) Urinary tract infections 38 (30 45) Skin Infections 35 (31 40) Viral upper respiratory infection 26 (21 31) Bronchitis 25 (20 30) Fleming-Dutra K et al. JAMA. 2016; 315(17): 1864-73 20 Antibiotics for URTIs Among most common reason for antibiotic misuse Viral etiology most common 90% of bronchitis cases due to virus Only 20% of pharyngitis cases due to S. pyogenes Antibiotics indicated in cases of severe symptoms (T>102F, facial/ear pain with purulent discharge) Use of watchful waiting or delayed therapy Linder et al. Arch Intern Med 2006, Ebell et al. JAMA 2000 Antibiotic use in the ED Wide range of clinical symptoms for which antibiotics are given in the ED Upper/lower respiratory tract infections Donnelly et al. (retrospective cohort, 10 years) 61% of all pts with respiratory infection in ED prescribed an antibiotic (all use) 48% with inappropriate indication received antibiotic (e.g. bronchitis, influenza) Donnelly J et al. Antimicrob Agent Chemother. 2014. 58(3): 1451-7; Minderhoud et al. Netherlands J Med. 2017. 75 (5). 21 22 It s Complicated. Enter the Pharmacist Rx Rx Rx 4

CC: SOB and cough Patient Case HPI: DO is a 82yo male who presented to the hospital ED complaining of productive cough with white sputum lasting 2 days with gradually worsening shortness of breath. PMH: COPD, CAD, T2DM, HTN, hyperlipidemia, STEMI, pneumonia, CKD stage 3 SH: former smoker (1 ppd), no alcohol use Allergies: morphine (anxiety) Diagnosis: r/o community acquired pneumonia Home Medications Benzonate 150mg: take 1 cap PO BID Carvedilol 6.25mg: take 1 tab PO BID Chlordiazepoxide HCl 10mg: take 1 tab PO TID PRN Fenofibrate 160mg: take 1 tab daily w food Advair (Fluticasone- Salmeterol 250-50mcg/dose: 1 puff BID Furosemide 30mg: take 1 tab PO daily Warfarin 4mg po daily Linagliptin 5mgL take 1 tab po daily Lisinopril 20mg take 1 tab PO daily Metformin 500mg : take 1 tab PO BID w meals Nitroglycerin 0.4mg SL tab: dissolve 1 tab under the tongue every 5 minutes as needed for chest pain Definitions Community-acquired pneumonia (CAP) Cases of infectious pneumonia in patients living independently in the community Hospital-acquired pneumonia (HAP) Onset occurs> 48hrs after admission Ventilator-associated pneumonia (VAP) Onset>48 72hrs after endotracheal intubation CAP-Background CAP Incidence: 12 cases per 1000 persons 1.1 million hospitalizations/year ~50,000 deaths/year > 10% mortality rate Overall yearly cost: 9-10 billion dollars Mean hospital charge for managing CAP per case: 25,000+ dollars 10% of patients with CAP require ICU admission Kalil AC et al. Clin Infect Dis 2016;63:1-51 Kollef M, et al. Chest 2005;128:3854-3862 CDC. Pneumonia. Available at: w www.cdc.gov/nchs/fastats/pneumonia.htm. Updated April,2013. Harrisons Principles of Internal Medicine. 18th edition, 2010.Mandell LA et al. Clin Infect Dis 2007;44:S27-72 CAP-Background Important cause of morbidity and mortality Despite advances in antimicrobial therapy, better supportive care, and preventive measures A leading cause of death worldwide and the leading cause of death in the U.S. The classification of pneumonia is increasingly complex as the patient population becomes more diverse Changing patient characteristics and location in which health care is administered Murphy SL, et al. Deaths: Final data for 2010. National vital statistics reports; vol 61 no 4. Hyattsville, MD: National Center for HealthStatistics.2013 Pathogenesis Introduction of the pathogen to the lung Aspiration of oropharyngeal secretions Most common Most people (healthy & ill) routinely aspirate oropharyngeal secretions during sleep Aerosolization/Inhalation Hematogenous Pneumonia develops Defense mechanisms are impaired Host is over come by inoculum Virulent organism Ellis on RT III and Donowitz GR. Acute Pneum onia. In Mandell, Douglas, and Bennett s Principles and Practice of InfectiousDiseases,8th ed.(2015) Philadelphia;ElsevierSaunders 5

Vitals Ht: 1.83m (6 ) Wt: 101.6kg ; BMI : 30.38 kg/m 2 Temp: 98.8F (or 37.1 C) BP: 140/68 P: 81 RR:18 O2 saturation 95% Metabolic panel 2/7/18 2/8/18 Glucose 178 202 BUN 38.5 53.3 Creatinine 1.4 1.7 Na 141 139 K 5.5 (H) 5 egfr 48.4 38.7 Patient Case CBC 2/7/18 2/8/18 WBC 11.05 (H) 9.87 Hgb 14.6 14.5 Plt 129 (L) 133 (L) RBC 4.95 5.12 Auto differential 2/7/18 2/8/18 Neutrophil 89.6 89.1 Lymphocytes 5.1 4.5 Monocyte 4.4 5.6 Neutro# 9.9 (H) 8.8(H) Absolute immature 0.09 (H) 0.08(H) Patient Case X-ray: mild atelectasis or fibrosis at the lung base CT chest: Low lung volume Calcified pleural plaques in the inferior chest associate with pleural thickening and persistent basilar atelectasis or scarring Cultures: Sputum: no growth Blood cultures: no growth Nasal swab: MRSA positive Influenza A & B: negative Clinical Diagnosis Chest X-ray New or progressive infiltrate Multilobar involvement indicates severe disease Clinical findings Fever(>38 o C), purulent sputum, leukocytosis Decline in oxygenation, worsen respiratory status Unexplained hemodynamic instability or deterioration of blood gases during mechanical ventilation Difficult diagnosis to confirm Congestive heart failure or underlying lung disease complicate diagnosis Clinical Diagnosis Cultures Sputum culture Colonization vs. pathogen; results less reliable Lower respiratory tract culture i.e. Bronchoalveolar lavage (BAL) Blood culture Rule out extra-pulmonary infection Simplified Microbiology: 5 Classes 1. Gram (+) cocci Staph Strep Enterococcus 2. Gram (-) cocci and bacilli Neisseria H. flu M. cat 3. Enterobacteriaceae 1. EKP: E.coli, Klebsiella, Proteus 2. ESC: Enterobacter, Serratia, Citrobacter 4. Pseudomonas aeruginosa 5. Anaerobes: Bacteroides fragilis Pathogens in CAP Outpatient Inpatient non-icu Inpatient ICU S. Pneumoniae H. Influenzae M.Pneumoniae C. Pneumoniae Resp. viruses S. Pneumoniae H. Influenzae M.Pneumoniae C. Pneumoniae Resp. viruses Legionella spp. Anaerobes (aspiration) S. Pneumoniae H. Influenzae Legionella spp. Gram negative rods S.aureaus Influenza A and B, adenovirus, RSV, parainfluenza Adaptedfrom: 6

Drug-Resistant Streptococcus pneumoniae (DRSP) Risk factors for beta-lactam resistant Strept. pneumoniae Age:<2years or >65years Beta-lactam therapy within previous 3 months Alcoholism, medical co-morbidities, immunosuppression, exposure to child in day care center Resistance to fluoroquinolones and macrolides related to repeated courses of same antibiotic Higher doses of penicillin and fluoroquinolones may overcome reduced susceptibilities however, switching to more potent agents preferred to prevent emergence of resistance Considerations for Initial Empiric Antimicrobial Therapy Institutional or unit specific susceptibility patterns Patient specific factors Allergies Recent antibiotic exposure Recent hospitalization or healthcare-related facility Previous culture results MDR pathogens Comorbidities Concomitant medications Antimicrobial factors Adverse effects Administration (IV or PO) Collateral damage Cost/availability Drug interactions Formulary restrictions Penetration to site of infection PK/PD profile Spectrum of activity Empiric Therapy-CAP Determine Site-of-Care: Outpatient versus inpatient CURB-65: Confusion, uremia, respiratory rate, low blood pressure, age > 65 If score > 2, admit to hospital (higher risk for mortality) General ward versus ICU ICU admission required inpatients in septic shock requiring vasopressors, patients requiring mechanical ventilation Admit to ICU if 3 minor criteria for severe CAP met Patient Case Confusion 0 BUN >20 mg/dl 1 Respiratory rate 30 breaths/min 0 Blood pressure (systolic <90 mmhg, or diastolic 60 mmhg) 0 Age 65 years 1 CURB-65 total score 2 Empiric Therapy-CAP Co-morbidities Chronic heart, lung, liver, renal disease; diabetes, alcoholism, malignancies, asplenia, immunecompromised state, antibiotic use within past 3 months, or other risks for DRSP Regional rate of drug-resistant Streptococcus pneumoniae (macrolides, penicillin) Potential Pathogens/DRSP risk Streptococcus pneumoniae previously healthy Mycoplasma pneumoniae Chlamydophila pneumoniae Haemophilus influenzae Streptococcus pneumoniae presence of co-morbidities Mycoplasma pneumoniae Chlamydophila pneumoniae Haemophilus influenzae CAP-Outpatient Recommended Therapy MACROLIDE Azithromycin, clarithromycin DOXYCYCLINE BETA LACTAM Amoxicillin 1gm q8h, amoxicillinclavulanate 2g q12hrs, ceftriaxone, cefpodoxime, cefuroxime PLUS Macrolide Doxycycline Respiratory fluoroquinolone - levofloxacin, moxifloxacin 7

CAP-Inpatient Admission Non ICU CAP-ICU Admission Potential Pathogens/DRSP risk Streptococcus pneumoniae Mycoplasma pneumoniae Chlamydophila pneumoniae Haemophilus influenzae Legionella spp. Aspiration Recommended Therapy BETA LACTAM Cefotaxime, ceftriaxone, ampicillin PLUS Macrolide Doxycycline Respiratory fluoroquinolone levofloxacin, moxifloxacin Potential Pathogens/DRSP risk Streptococcus pneumoniae Legionella spp Haemophilus influenzae Gram-negative rods Recommended Therapy BETA LACTAM Cefotaxime, ceftriaxone, ampicillin/sulbactam PLUS Macrolide (azithromycin) Respiratory fluoroquinolone PLUS aztreonam If PCN allergic Respiratory fluoroquinolone PLUS aztreonam CAP-Pseudomonas and MRSA Coverage Potential Pathogens/DRSP risk Pseudomonas aeruginosa (Risk factors: Structural lung disease, severe COPD, frequent steroid or abx use, prior abx) Community-acquired MRSA (Risk factors: End-stage renal disease, IV drug use, prior influenza, prior abx use (esp. fluoroquinolones) Recommended Therapy Anti-pseudomonas beta lactam Azithromycin, clarithromycin PLUS Anti-pseudomonas fluoroquinolone Aminoglycoside PLUS azithromycin Anti-pneumococcal fluoroquinolone PLUS aminoglycoside ADD Vancomycin Linezolid Duration of Therapy-CAP Minimum of 5 days Consider 7 days if structural lung disease and/or immunocompromised Afebrile for 48-72 hrs and have 1 CAP associated clinical instability before discontinuing therapy Temp 37.8 C HR 100bpm Respiratory rate 24bpm SBP 90 O 2 saturation 90% Ability to maintain oral intake Normal renal status Antibiotic class Beta-lactam (Penicillin) Macrolides Fluoroquinolones Mechanism of Resistance Altered penicillinbinding protein (PBP) Active efflux (mefe), ribosomal modification (ermb) Target site mutations on DNA gyrase and topoisomerase II DRSP Prevalence of Resistance Risk Factors 15* Age<2, or>65 Antibiotic therapy w/in previous 3 months; alcoholism; medical comorbidities; immunosuppression; daycare 44%* Recent therapy with macrolides Rare (<2%)* Jones RN, et al. Diag Microbiol Infect Dis 2013:75:107-109 Mandell LA et al. Clin Infect Dis 2007;44:S27-72 Recent therapy with FQs Inova PNA Protocol CAP, Non-ICU Admission without pseudomonas risk factors Levofloxacin 750mg IV/PO x 5 days Ceftriaxone 1g IV Q24h x 7 days AND Azithromycin 500mg PO/IV daily x 5 days CAP, ICU Admission without pseudomonas risk factors Levofloxacin 750mg IV Q24h x 7 days AND Ceftriaxone 1g IV Q24h x 7 days Ceftriaxone 1g IV Q24h x 7 days AND Azithromycin 500mg IV Q24h x 5 days HCAP with pseudomonas risk factors Cefepime 2g IV AND Levofloxacin 750mg IV Piperacillin/Tazobactam 4.5g IV AND Levofloxacin 750mg IV CAP/HCAP with MRSA risk factors Vancomycin with trough level goal of 15mg/kg IV for 120 minutes CAP/HCAP with suspected aspiration Clindamycin 600mg IV q8h 8

Patient Case CAP Inpatient treatment Azithromycin 250mg IV Q24h x 5 days Ceftriaxone 1g IV Q24h x 7 days Lactobacillus/Streptococcus cap: take 1 cap PO daily BUGS AND DRUGS F CAP Penicillins 1. Natural Penicillins 2. Penicillinase-resistant Penicillins 3. Aminopenicillins 4. Extended-Spectrum Penicillins 5. Beta-lactam/Beta-lactamase inhibitors Penicillins Adverse Reactions to Penicillins Allergic Gastrointestinal Hematologic Hepatic Electrolyte disturbance Neurologic Renal Penicillins Natural Penicillins Penicillin VK Penicillin G Penicillinase-resistant Penicillins Nafcillin Oxacillin Dicloxacillin Aminopenicillins Ampicillin (Principen ) 0.25-0.5gm Q6h PO or 1-2gm IV Q4-6h Amoxicillin (Amoxil, Polymox ) 250mg-1gm Q8h PO or 500mg-875mg PO Q12h 90mg/kg/day (children) Amoxicillin extended release (Moxatag ) 775mg QD 9

Aminopenicillins Spectrum of Activity Gram positive coverage Streptococcus sp, Listeria monocytogenes, Enterococcus Increased gram negative coverage Shigella, E. Coli, Haemophilus influenzae (non betalactamase), Proteus mirabilis, Neisseria meningitidis, Pasteurella multocida Clinical Uses Upper respiratory tract infections such as acute otitis media and streptococcal pharyngitis Enterococcal infections Prophylaxis against endocarditis before dental procedures Beta-lactam/Beta-lactamase inhibitors Amoxicillin/clavulanic (Augmentin ) Tab: 250mg/125mg Q8h PO, 500mg/125mg Q8h PO, 875mg/125mg PO Q12h PO, XR 1000mg/62.5mg x 2 BID PO Chewable Tab: 200mg/28.5mg, 400mg/57mg Susp: 125mg/5ml-31.25mg/5ml; 200mg/5ml-28.5mg/5ml; 250mg/5ml-62.5mg/5ml; 400mg/5ml-57mg/5ml; 600mg/5ml- 42.9mg/5ml Coverage: Staphylococus aureus, Streptococcus, Enterococcus, Enteric gram negatives, many anaerobes Clavulanic acid ADR s: diarrhea, hepatotoxicity Clinical Uses: Respiratory: refractory otitis media, sinusitis, CAP Skin and skin structure, diabetic ulcers, bite wounds Beta-lactam/Beta-lactamase inhibitors Ticarcillin/clavulanic acid (Timentin ) 3.1g Q4-6h IV Piperacillin/ Tazobactam (Zosyn ) 3.375g Q6H IV or 4.5g Q8H IV Clinical Uses Pseudomonas coverage Aspiration pneumonia Severe intra-abdominal infections Mixed infections Cephalosporins Adverse Reactions Hypersensitivity reactions Hematologic reactions Coagulation abnormalities Gastrointestinal reactions Nephrotoxicity Phlebitis Disulfiram-like reaction 1 st Generation Cephalosporins : Cefazolin (Ancef, Kefzol ) 1-2gm IV/IM Q8h Cephalexin (Keflex) 0.25-1gm Q6h PO Cefadroxil (Duricef) 0.5-1gm Q12h PO Drug of Choice: Skin and skin structure infections (cellulitis, impetigo) Spectrum of activity: Staphylococcus aureus (including beta-lactamase producing strains), not MRSA Streptococcus Fair enteric gram negatives (E. Coli, Klebsiella, Proteus) 2 nd Generation Cephalosporins Cefoxitin (Mefoxin) IV 1-2gm Q6-8h Cefuroxime (Zinacef) IV/IM 0.75-1.5gm Q8h and cefuroxime axetil (Ceftin) PO 0.125-0.5gm Q12h Cefotetan (Cefotan) IV/IM 1-3gm Q12h Cefaclor (Ceclor) PO 0.25-0.5gm Q8h; Cefaclor ER PO 0.5gm Q12h Cefprozil (Cefzil) PO 0.25-0.5gm Q12h Spectrum of activity compared to 1 st generation Increased gram negative coverage H. influenza, Neisseria, Moraxella, E. Coli, Klebsiella, Proteus Decreased gram positive coverage Oral agents are good for treatment of refractory otitis media and sinusitis, Cefuroxime used for CAP 10

3 rd Generation Cephalosporins Cefotaxime (Claforan) IV/IM Ceftizoxime (Cefizox) IV/IM Ceftazidime (Fortaz) IV/IM Cefibuten (Cedax) PO Cefdinir (Omnicef) PO Cefpodoxime (Vantin) PO Ceftriaxone (Rocephin) IV/IM Cefixime (Suprax) PO Cefditoren pivoxil (Spectracef) PO 3 rd Generation Cephalosporins Spectrum of activity Increased gram negative coverage Decreased gram positive coverage No anaerobic coverage Cefriaxone Agent of choice for Neisseria meningitidis Often used for inpatient CAP Excellent CNS penetration (Q12h) No adjustment for renal function; QD drug ADR: pseudocholelithiasis Good gram negative coverage, good Streptococcus coverage Caution in neonates <30d because of lack of enzymes to conjugate Fluoroquinolones Fluoroquinolones Consider second line to beta-lactam based therapy? Disadvantages of fluoroquinolones FDA warning: Risk of toxicity outweighs benefit in management of uncomplicated infections (cystitis, bronchitis, sinusitis) FDA warning: Increased risk of severe neuropathies Dysglycemia among diabetics QTc prolongation risk Acute kidney injury Association with Clostridium difficile Increasing fluoroquinolone gram-negative resistance Drug interactions Quinolones absorption reduced by: di-, tri-valent cations (antacids, Ca supplements, iron, MVI, diary products, etc.), sucralfate, DDIs Space out at least 2h Ciprofloxacin can inhibit metabolism of: theophylline, caffeine Warfarin Concomitant QT prolongation with antiarrhythmic Opiate screen false positives 2 nd Generation Fluoroquinolones Ofloxacin Norfloxacin Ciprofloxacin Good for UTIs, pyelonephritis, prostatitis, osteomyelitis, anthrax, infectious diarrhea, travelers diarrhea, typhoid fever, intraabdominal infections (with drug to cover anaerobes) Dosing: PO 250-500-750mg BID XR 500-1000mg QD IV 400mg Q8-12h Ophthalmic solution 0.3% 3 rd Generation Fluoroquinolones Levofloxacin (Levaquin) Improved Gram + coverage and similar Gram, some Pseudomonas coverage Used for CAP, COPD exacerbations, sinusitis, skin infections, complicated UTIs Respiratory fluoroquinolone Dosing: 250mg-750mg PO/IV Q24h Ophthalmic solution (Iquix 1.5%, Quixin 0.5%) 11

3 rd Generation Fluoroquinolones Moxifloxacin (Avelox) No renal adjustment, no urinary penetration Gram negative and positive coverage (high activity for Streptococcus pneumoniae (MDRSP), anaerobes Uses: pneumonia, AECB, sinusitis, intra-abdominal infections, skin/skin structure Respiratory Fluoroquinolone Dosing: 400mg IV/PO Q24h Ophthalmic 0.5% (Vigamox) 3 rd Generation Fluoroquinolones Gemifloxacin (Factive) Similar in coverage to other 3 rd generation FQ (not pseudomonas, not anaerobes) Uses: pneumonia, AECB Respiratory fluoroquinolone ADR s: Rash Dosing: 320mg PO Q24h Delafloxacin (Baxdela ) Approved June 19, 2017 FDA approved for treatment of acute bacterial skin and skin structure infections Macrolides Food decreases absorption Excreted in bile Adverse effects IV phlebitis GI N/V/D and abdominal cramps Drug Interactions: Benzos Carbamazepine Cyclosporine Lovastatin, simvastatin, atorvastatin Theophylline Colchicine Macrolides Clinical uses Upper and lower respiratory tract infections Chlamydia trachomatis Atypical mycobacterial infections Traveler s diarrhea (azithromycin) H. pylori (clarithromycin) Macrolides The Trouble with Transitions Clarithromycin PO: 500mg q12h; 2x500mg Q24h (Biaxin XL) Renal adjustment required Check for drug interactions Azithromycin Dosing: PO: 500mg QD x 3 (Zithromax Tri-Pak); 500mg x 1 then 250mg QD x 4 (Zithromax Z-Pak); 2gm x 1 (oral suspension) (Zmax); 1gm x 1 IV: 500mg IV Q24h Prolonged half-life allowing for shorter courses No renal adjustment necessary Least drug interactions 12

Patient Case DO was discharged on Day 3 Discharge medications for CAP Levofloxacin 750mg po daily x 5 days Lactobacillus/Streptococcus cap: take 1 cap PO daily Questions? 13