Outline. What bug is causing my patient s infection? Before you prescribe an antibiotic. There are times.

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1 Infectious Disease Update: Are the Bugs Winning? Speaker has no relationship to disclose. Amelie Hollier, DNP, FNP-BC, FAANP President, APEA Outline Utilize the most current evidence based guideline to treat common bacterial infections. Be able to discuss current patterns of antibiotic resistance. Describe newly developed antibiotics and their advantages for use in treatment of common infections. Before you prescribe an antibiotic. There is a question you MUST ask What bug is causing my patient s infection? What are the most likely bugs? There are times. We HAVE to get a culture The patient can t afford treatment failure! 1

2 Since we can t culture every bug Lung Infections Community Acquired Pneumonia (CAP) CAP post influenza Acute Bronchitis We have to be pretty good at Empiric Treatment! 52 year old female, ND, a retired school teacher, has been diagnosed with CAP. She is a non-smoker, has normal BMI, takes no meds. She walks 3 miles, 4-5 times weekly. What s the most likely pathogen for her CAP? 1. Strept pneumoniae 2. Atypical pathogen 3. Staph aureus 4. Viral pathogen 52 year old female, ND, a retired school teacher, has been diagnosed with CAP. She is a non-smoker, has normal BMI, takes no meds. Most common cause is an atypical pathogen: Mycoplasma pneumoniae; could be viral; could be S. pneumo but these 2 are much less likely What is an acceptable treatment for the most likely pathogen? 1. Azith 500 mg once, then 250 mg x 4 days 2. Azith 2g once 3. Doxycycline 100 mg PO BID 4. Amox-clav 875 PO mg BID If Mycoplasma is documented as the pathogen, what the best treatment? 2

3 If Mycoplasma is documented as the pathogen, what the best treatment? 1. Azith 500 mg once, then 250 mg x 4 days 2. Azith 2g once 3. Doxy 100 mg PO BID 4. Amox-clav 875 PO mg BID JAC 68:506, 2013 Increasing macrolide resistance with Mycoplasma Doxy is a superior choice JAC 68:506, 2013 Suppose ND developed CAP post influenza infection? What s the most likely pathogen for her CAP? 1. Strept pneumoniae 2. Atypical pathogen 3. Staph aureus 4. Viral pathogen What is an acceptable treatment for the most likely pathogen? 1. Levofloxacin 750 mg PO daily 2. Azithromycin 2g once 3. Doxy 100 mg PO BID 4. Amox-clav 875 mg PO BID Suppose she was quinolone allergic or couldn t take a quinolone (and had post-flu pneumonia)? Azith or Clarith Plus HD amox, HD amox-clav, cefdinir (Omnicef), cefpodoxime (Vantin), cefprozil (Cefzil) FYI: if use a ceph, always give the BID dose! How much amox is considered HIGH DOSE? Amox: 1 gram PO TID Amox-clav: Use Amox-clav ER (1000/62.5) Prescribe 2 tabs BID 3

4 52 year old female, ND, a retired school teacher, has been diagnosed with CAP. Suppose she has COPD and smokes 1 PPD. What s the most likely pathogen for her CAP if she has COPD? 1. Strept pneumoniae 2. M. catarrhalis 3. H. influenzae 4. Viral pathogen So, knowing the most likely bug is helpful in choosing the best antibiotic! What s an easy way to remember which antibiotic to give for CAP? CAP in an Adult Give a macrolide or doxy first line UNLESS.. CAP in an Adult The patient has a co-morbid: Alcoholism Bronchiectasis COPD Post-CVA aspiration Post-influenza Significant chronic disease 4

5 CAP in an Adult If co-morbid is present: Respiratory quinolone Gemifloxacin (Factive) 320 mg Levofloxacin (Levaquin) 750 mg Moxifloxacin (Avelox) 400 mg Respiratory Quinolones Ciprofloxacin no longer considered a respiratory quinolone R/T increased rates of resistance: S. pneumoniae Pseudomonas aeruginosa C. difficile N. gonorrhoeae MRSA, MSSA S. aureus Prescribers Letter 2011; 18(5): What do Tequin, Raxar, Zagam, and Trovan all have in common? Hint: They all were quinolones. Remember These? Tequin (gatifloxacin): blood sugar irregularities Zagam (sparfloxacin): phototoxicity and QT prolongation Trovan (trovafloxacin): hepatotoxicity Quinolones as a Class Blood sugar level issues! QT prolongation CNS adverse effects (dizziness, etc.) Tendon rupture (rare) FDA Bulletin May, 2016 Safety Labeling Changes serious side effects associated with FQs generally outweigh the benefits for patients with acute sinusitis, acute bronchitis, and uncomplicated UTI who have other treatment options FQs should be reserved for people who have no alternative treatment options Prescribers Letter 2011; 18(5): FDA Bulletin; Updated 6/7/16 5

6 FDA Bulletin May, 2016 What Side effects? Serious side effects involving the tendons, muscles, joints, nerves, and CNS stop systemic FQ treatment immediately if a patient reports serious side effects Things to Remember! None approved in children* Do not use in pregnant patients Separate from Mg, Al, sucralfate, Fe, Zn (Ca probably OK but not with cipro):drug specific No sig CYP450 interactions except with cipro FDA Bulletin; Updated 6/7/16 Prescribers Letter 2011; 18(5): Ciprofloxacin Ciprofloxacin is a 1A2 med Combined with theophylline, xanthines (CAFFEINE), results in increased plasma concentrations of the co-administered drug So what happens??? Prescribers Letter 2011; 18(5): Respiratory Quinolones What would make you choose one over the other? Gemifloxacin (Factive) 320 mg Levofloxacin (Levaquin) 750 mg Moxifloxacin (Avelox) 400 mg Prescribers Letter 2011; 18(5): Levofloxacin Diminished activity against Strept pneumo and anaerobic pathogens Levofloxacin originally dosed at 500 mg daily but increased to 750 mg daily to improve coverage against resistant organisms Respiratory Fluoroquinolones 3rd Generation Levofloxacin (Levaquin) Gram Positives, Gram Negatives, Atypical Pathogens, DRSP, many aerobes, some anaerobes Prescribers Letter 2011; 18(5): Staph: MSSA Listeria Strept: all; M. cat, H. flu, E. coli, Legionella, Chlamydophila, Mycoplasma, Klebsiella, + Pseudomonas, 6

7 Respiratory Fluoroquinolones Staph: MSSA Listeria Not urinary pathogens 4th Generation Moxifloxacin* (Avelox) Gemifloxaxin (Factive), Gatifloxacin (Zymar ophth) Gram Positives, Atypical Pathogens, superior pneumococcus and anaerobic coverage Strept: all; M. cat, H. flu, E. coli, Legionella, Chlamydophila, Mycoplasma, Klebsiella * GI pathogen coverage Take Home Point A 4 th generation quinolone would be a better choice than a 3 rd gen quinolone for DRSP Prescribers Letter 2011; 18(5): Patient #2 38 year old male, otherwise healthy has been diagnosed with acute bronchitis. He is a nonsmoker, has BMI 29, has well controlled HTN, lipids. What s the most likely pathogen for his acute bronchitis? 1. Strept pneumoniae 2. Atypical pathogen 3. Staph aureus 4. Viral pathogen Patient #2 Acute Bronchitis 90% viral 5% M. pneumoniae 5% C. pneumoniae Antibiotics are NOT indicated usually! JAMA 312:2678, 2014 When might antibiotics be indicated? Associated sinusitis Heavy growth on throat culture for S. pneumo, Group A Strept, H. flu No improvement in 1 week Otherwise, treatment is SYMPTOMATIC! Acute Bronchitis Expect cough to last 2 weeks (<20 days) Purulent sputum is not an indication for antibiotic treatment JAMA 312:2678, 2014 JAMA 312:2678,

8 Quiz Why do most patients with acute bronchitis have purulent looking sputum? Purulent Sputum IF patient has fever, rigors, systemic symptoms, get chest x-ray JAMA 312:2678, 2014 Urinary Tract Infection If Local resistance rate < 20% TMP-SMX BID x 3 days Add phenazopyridine (Pyridium) Local resistance rate correlates with clinical failure TMP/SMX Drug Interactions You ll see this as a New Drug Interaction in your Smart Phone Apps! Possible HYPERKALEMIA when TMP-SMX combined with meds that increase potassium ACEs, ARBs, potassium sparing diuretics, NSAIDs JAMA 312:1677, 2014 Prescribers Letter; January 2015; Vol31 TMP/SMX Drug Interactions Trimethoprim decreases excretion of potassium (acts on the distal nephron, blocking the epithelium Na channel which leads to reduction in renal excretion of K) Hyperkalemia develops 4-5 days after taking TMP/SMX, so 3 day dose likely OK TMP/SMX Drug Interactions 81.5% had significant increase in serum K from baseline 18% had hyperkalemia > 5 meq/l 6% had hyperkalemia > 5.5 meq/l Reversible once TMP/SMX is d/c d Prescribers Letter; January 2015; Vol31 Alappan R, Buller GK, Perazella MA. Trimethoprim-sulfamethoxazole therapy in outpatients: is hyperkalemia a significant problem? Am J Nephrol1999;19:

9 Drug Interactions 6% of patients on TMP/SMX develop hyperkalemia Hospitalizations increase 7-fold when elders take TMP-SMX with ACE, ARB, etc Even higher when combined in patients who take ACEs, ARBs, or spironolactone Care in These Patients! Elderly Renal insufficiency DM Heart failure ***If no alternative to TMP/SMX, check K level after day 3 Prescribers Letter; January 2015; Vol31 Prescribers Letter; January 2015; Vol31 So UTI If Local resistance rate < 20% TMP-SMX BID x 3 days Add phenazopyridine (Pyridium) Why are we adding phenazopyridine? Local resistance rate correlates with clinical failure JAMA 312:1677, 2014 JAMA 312:1677, 2014 Urinary Tract Infection IF Local resistance rate > 20% or sulfa allergy: Nitrofurantoin 100 mg PO BID x 5 days Fosfomycin single 3g dose *Ciprofloxacin 250mg BID or 500 mg ER q24h *Levofloxacin 250 mg q24 Add phenazopyridine (Pyridium) Urinary Tract Infection IF Local resistance rate > 20% or sulfa allergy: Ciprofloxacin 250mg BID or 500 mg ER q24h Levofloxacin 250 mg q24 Why aren t the 4 th generation quinolones used to treat UTIs? JAMA 312:1677, 2014 Drug package inserts: Moxifloxacin, Gemifloxacin 9

10 Lets talk about Nitrofurantoin IF Local resistance rate > 20% or sulfa allergy: Ciprofloxacin 250mg BID or 500 mg ER q24h Levofloxacin 250 mg q24 Nitrofurantoin 100 mg PO BID x 5 days Fosfomycin single 3g dose Add phenazopyridine (Pyridium) Mrs. Jones is 75 years old. She is diagnosed with a UTI. Her CrCl is 50 ml/min. What drug might be a good choice for her? JAMA 312:1677, Beers Criteria Update Expert Panel J AM GeriatrSoc. 2012;60(4): Mrs. Jones is 75 years old. She is diagnosed with a UTI. Her CrCl is 50 ml/min. Which anti-infective should be avoided in her because of inadequate drug concentration in the urine? 1. Sulfa drug (none as long as CrCl > 30 ml/min) 2. Ciprofloxacin (none as long as CrCl > 30 ml/min) 3. Nitrofurantoin (AVOID!) Mrs. Jones is 75 years old. She is diagnosed with a UTI. Her CrCl is 50 ml/min. Beers Criteria recommends nitrofurantoin avoidance: CrCl < 60 ml/min For long-term suppression 2012 Beers Criteria Update Expert Panel J AM GeriatrSoc. 2012;60(4): Nitrofurantoin IF used for daily prophylaxis, may cause pulmonary toxicity, neuropathy, or hepatotoxicity. Etiology of Acute Sinusitis Most common??? Hooton TM, Bradley SF, Cardenas DD, et al. Diagnosis, prevention, and treatment of catheter-associated urinary tract infection in adults: 2009 International Clinical Practice Guidelines from the Infectious Diseases Society of America. Clin Infect Dis2010;50: Dailymed.nlm.gov; Nitrofurantoin product insert 10

11 Etiology of Acute Sinusitis Obstruction of the sinus ostia by inflammation from virus or allergy Treatment: Saline irrigation IF Pathogen present: S. pneumoniae 33% H. influenzae 32% M. catarrhalis 9% Anaerobes 6% Grp A Strep 2% Viruses 15-18% S. aureus 10% S/S Bacterial Infection Fever Pain Purulent nasal discharge Still symptomatic after 10 days with no antibiotic Clinical failure despite antibiotic treatment IF Pathogen present: S. pneumoniae 33% H. influenzae 32% M. catarrhalis 9% Anaerobes 6% Grp A Strep 2% Viruses 15-18% S. aureus 10% What Antibiotic for ABRS? Amoxicillin not a good first choice (too much resistance, less Strept pneumo, more incidence of H. flu) Empiric: Amoxicillin-clavulanate (500 TID or 875 BID) Amoxicillin-clavulanate (2g BID) in areas where DRSP likely CID 54:e72, 2012 Penicillins Extended Spectrum PENICILLINS Amoxicillin/Clavulanic acid (Augmentin) Gram Positives, Gram Negatives Β- lactamase, NOT MRSA What bug do smokers harbor? H. influenza (40%) M. catarrhalis (90%) 11

12 What if PCN allergic? Doxycycline (alternative first line tx PCN allergy) *Resp FQ for PCN allergic patients No Macrolides: 30% resistance rate! TMPS, 2 nd or 3 rd gen cephs NOT recommended What Antibiotic for Peds? First line: Amoxicillin with or without clavulanate Alternatives: cefdinir, cefuroxime, cefpodoxime Avoid sulfa drugs, azithromycin Wald ER, Applegate K E, BordleyC, et al. Clinical practice guideline for the diagnosis and management of acute bacterial sinusitis in children 1 to 18 years. Pediatrics 2013;132:e262 e Duration Eradication if on appropriate antibiotic in 72 hours but treat days (no longer treat days) With shorter courses: equal efficacy, fewer complications, no increased risk of relapse Better compliance! Can PCN allergic patients safely receive cephalosporins? 2 Issues There MUST be a PCN allergic reaction!!! True Allergic Reaction IgE mediated (type 1 hypersensitivity reaction) 12

13 Morbilliform Rash Rash is macular or maculopapular, lesions are fixed, area expands over several days May itch More prevalent in children More common with aminopenicillins (amox and ampicillin) Morbilliform Rash Usually T-cell mediated Concurrent viral infections predispose patients to morbilliform rash Unknown mechanism by which this occurs The rash is Not IgE-mediated if neither urticarial nor pruritic!!! And there is NO increased risk of the same rash recurring with repeated courses of the same antibiotic. Second Issue How significant is the crosssensitivity reaction? Journal of Family Practice, Feb Likely Allergy to Cephalosporins after allergy to PCN Very likely to have SAME allergic reaction with these drugs because they share a similar R side chain Pen G Amoxicillin Ampicillin Journal of Family Practice, Feb Cefaclor Cephalexin Cefprozil Cefadroxil Ceftriaxone Cefpodoxime Likely Allergy to Cephalosporins after allergy to PCN Cephalexin (1 st gen) Cefadroxil (1 st gen) Cefaclor (2 nd gen) Cefprozil (2 nd gen) Ceftriaxone (3 rd gen IM) Cefpodoxime (3 rd gen ) 13

14 UNLIKELY Allergy to Cephalosporins after allergy to PCN NOT likely to have SAME allergic reaction with these drugs because they are dissimilar in structure Cefazolin Cefuroxime Cefdinir Cefixime Ceftibuten UNLIKELY Allergy to Cephalosporins after allergy to PCN Cefazolin (1 st gen IM) Cefuroxime (2 nd gen) Cefdinir (3 rd gen ) Cefixime (3 rd gen ) Ceftibuten (3 rd gen ) Journal of Family Practice, Feb RECOMMENDATION The risk of an allergic reaction is very low or non-existent if the side chains of the drugs are not similar. Journal of Family Practice, Feb Medications TMP-SMX Doxycycline/Minocycline Clindamycin Daptomycin (Cubicin) Linezolid (Zyvox) Tedizolid (Sivextro) Vancomycin Dalbavancin (Dalvance) Oritavancin (Orbactiv) Prescribers Letter; August 2014; Vol:30 Clindamycin (Cleocin) PO dose, 5-10 days: $10/day IV dose, 7-14 days: $25/day S/E: Myopathy, peripheral neuropathy Mycins Daptomycin (Cubicin) IV dose, 5-14 days: $200/day S/E: Myopathy, peripheral neuropathy Generic: June, 2016 Linezolid (Zyvox) Oral (generic now) or IV Severe purulent STI S/E: myeolosuppression/ serotonergic effects Weekly CBC required $275/day Zolids Tedizolid (Sivextro) Oral or IV Severe purulent SSTI S/E: thrombocytopenia No CBC required May have serotonergic effects $235/day IV; $295/day PO 14

15 Televancin (Vibativ) Cousin of vancomycin Longer duration than vanc S/E: Nephrotoxicity, red man syndrome $300/day, 7-10 days Vancins Dalbavancin (Dalvance) Cousin of vancomycin Longer duration than vanc 2 infusions one week apart S/E: Red man syndrome $4500/2 infusions Vancomycin (Vancocin) Requires blood levels Generic S/E: Red man syndrome $20/day, 7-14 days 10 Adult Recommendations (> 19 years old) Influenza Tdap Varice lla HPV Zoster MMR PCV 13, PPSV23 Meningococcal Hepatitis A, B Hib Impacting health of communities Pneumococcal Infection Most Common Diseases Pneumonia Meningitis Bacteremia ABRS OM Pneumococcal Disease Very common!!!! Pneumococcal disease spread by respiratory droplet Pneumococcal pneumonia fatality rate is 7% but higher in elderly, co-morbids 25-30% of pneumococcal pneumonia patients get bacteremia Pneumococcal Disease Pneumococcal disease is caused by Streptococcus pneumoniae There are 90 different serotypes (PPSV23 immunizes against 23 serotypes) Pneumococcal Vaccine: 2 Forms 13 valent; 23 valent 13 valent pneumococcal conjugate vaccine (PCV 13, Prevnar) 23 valent pneumococcal polysaccharide vaccine (PPSV23, Pneumovax) 15

16 Pneumococcal Vaccine: 13 valent 13 valent pneumococcal conjugate vaccine (PCV 13, Prevnar) Approved for 6 weeks to 18 years Approved > 50 years Pneumococcal Vaccine: 23 valent 23 valent pneumococcal polysaccharide vaccine (PPSV23, Prevnar) Approved for age > 2 years A 68 year old patient does not know whether he received a pneumococcal vaccine or not. How should this be handled? 1. Don t administer. 2. Administer now. PPSV 23: Who? Age 65 years or older with no or unknown history of prior receipt of PPSV Who else needs PPSV 23? Age years with no or unknown history of prior receipt of PPSV and any of the following: Cigarette smoker age 19 and older CV disease ( HF, cardiomyopathies, etc.) Chronic pulmonary disease (COPD, asthma) DM, alcoholism, chronic liver disease Candidate for a cochlear implant, CSF leak Functional or anatomic asplenia (SCA, splenectomy) HIV, congenital immunodeficiency, hematologic and solid tumors (immunocompromising conditions) Immunosuppressive therapy (alkylating agents, antimetabolites, long term systemic steroids, radiation therapy) Chronic renal failure or nephrotic syndrome; Solid organ or bone marrow transplantation PPSV23 and PCV13 Who gets a second PPSV 23? Functional or anatomic asplenia (SCA, splenectomy) HIV, congenital immunodeficiency, hematologic or solid tumors (immunocompromising conditions) Immunosuppressive therapy (alkylating agents, antimetabolites, long term systemic steroids, radiation therapy) Chronic renal failure or nephrotic syndrome; Solid organ or bone marrow transplantation These patients need PCV13 also!!!!!! 16

17 Facts to Remember PCV13: administer 12 months after PPSV23 PPSV23: administer (at least) 5 years after previous PPSV23 12 Pediatric Recommendations Influenza Rotavirus DTaP < 7 years TdaP > 7 years Varicella IPV MMR PCV 13, PPSV23 Meningococcal Hepatitis A, B Hib HPV What s new since 2016? Historic low in meningococcal disease incidence (0.18/100,000 persons) Current Quadrivalent vaccine covers (serogroups A, C, W, Y) Serogroup B meningococcal disease is rare but life threatening, not currently covered in quadrivalent vaccine MMWR, October 23, 2015 / 64(41); What s new since 2016? Recommendation All adolescents years: Administer MenACWY, single dose at years with a booster at age 16 years if first dose before age 16 years MenB may be administered to adolescents and young adults aged years ; preferred age: years MMWR, October 23, 2015 / 64(41); FDA licensed two MenB vaccines, June 2015 Approved in persons years MenB-FHbp (Trumenba) MenB-4C (Bexsero) Meningococcal Updates MMWR July 31, 2015 / 64(29);806 June 12, 2015 / 64(22); Meningococcal Vaccine FDA approved first serogroup B meningococcal (MenB) vaccine (MenB-FHbp [Trumenba, Wyeth Pharmaceuticals, Inc.]) as a 3-dose series January 2015, FDA approved a second MenB vaccine (MenB-4C [Bexsero, Novartis Vaccines]) as a 2-dose series Both vaccines were approved for use in persons aged years MMWR, October 23, 2015 / 64(41);

18 12 Pediatric Recommendations Influenza Rotavirus DTaP < 7 years TdaP > 7 years Varicella IPV MMR PCV 13, PPSV23 Meningococcal Hepatitis A, B Hib HPV HPV Update MMWR March 27, 2015 / 64(11); valent HPV Vaccine 9-valent human papillomavirus (HPV) vaccine (9vHPV) (Gardasil 9, Merck and Co., Inc.) as one of three HPV vaccines that can be used for routine vaccination HPV Update MMWR March 27, 2015 / 64(11); valent HPV Vaccine Recommended for routine vaccination at age 11 or 12 years ACIP also recommends vaccination for females aged 13 through 26 years and males aged 13 through 21 years not vaccinated previously. HPV Update MMWR March 27, 2015 / 64(11); valent HPV Vaccine Recommended through age 26 years for men who have sex with men and for immunocompromised persons (including those with HIV infection) if not vaccinated previously HPV Update MMWR March 27, 2015 / 64(11); valent HPV Vaccine 9vHPV is a noninfectious, virus-like particle (VLP) vaccine 9vHPV contains HPV 6, 11, 16, and 18 (like HPV4) Also contains HPV 31, 33, 45, 52, and 58 9vHPV targets five additional cancer causing types, which account for about 15% of cervical cancers HPV Update MMWR March 27, 2015 / 64(11); HPV Vaccines 2vHPV, 4vHPV, and 9vHPV all protect against HPV 16 and 18, types that cause about 66% of cervical cancers and the majority of other HPV-attributable cancers in the United States4vHPV and 9vHPV also protect against HPV 6 and 11, types that cause anogenital warts. 18

19 HPV Update MMWR March 27, 2015 / 64(11); HPV Vaccines 9vHPV and 4vHPV are licensed for use in females and males Bivalent HPV vaccine (2vHPV) contains HPV 16, 18, is licensed for use in females HPV Update MMWR March 27, 2015 / 64(11); HPV Vaccines 2vHPV, 4vHPV, and 9vHPV are each administered in a 3-dose schedule Suppose a 16 year old has received 2 previous doses with 4vHPV vaccine. Can 9vHPV be substituted for last dose of series? a. Yes b. No Quiz c. I m not sure Thank you! For questions or to contact me: Dr. Amelie Hollier amelie@apea.com Advanced Practice Education Associates 19