Diagnosis, Empiric Management and Prevention of Community-Acquired Pneumonia in Immunocompetent Adults TreatmentINTRODUCTION Internationally, community-aequired pneumonia (CAP) remains the leading cause of death from an infectious disease. Tis the sixth leading eause of death overall and is a major eause of morbidity sand mortality. Since the last publication of Philippine Clinical Practice Guidelines on the Diagnosis, Empiric: Management, and Prevention of Community-acquized Pneumonia (CAP) in Immunocompetent Adults in 2010, several changes had emerged ‘+ Multiple international societies had published and revised their guidelines of the management oF patients with CAP. + Neworanisms had emerged and development of resistance hnad increased over time among respiratory pathogens. + The influx and efflux of antimicrobial agents used in the treatment had Tikewise posed a threat to the rapid rise of antimicrobial resistance. The use, misuse, abuse and ‘overuse had also shaken the market of antimicrobial agents It is for these reasons that a long overdue’ update on the management of CAP is necded, There is a need to standardize care by providing management strategies based on best available evidences. The evidences may be the same; however, gional differences, causative agents, antibiotic resistance rates, drug licensing, ‘healtheare structure and available resources “may vary, Recommendations made by one national organization may therefore nur be applicable o ober counties ‘TREATMENT. ‘When shoutd antibiotics be initiated for the empiric treatment ‘of community-acquired pneumonia (CAP)? + Patients should receive inital therapy as soon as possible after the diagnosis is established Antibiotics, the meinstay forthe treatment of pneumonia, should be initiated as soon as a diagnosis of CAP is made, The 2004 PCPG for CAP recommended a maximum four-hour window‘Community Aequired Prevenonia from diagnosis to antimicrobial initiation, This recommendation ‘was based on studies that showed a reduced in-hospital mortality when antimicrobial therapy was initiated within the first four hours of admission anc diagnosis of CAP. The 2007 IDSA ATS Guidelines, however, found an internal inconsistency in outcomes between the group that received antibiotics within the first two hours and the group which received antibiotics two to four hours after diagnosis. Although therapy within 4 hours of arrival to the hospital has been associated with reduced mortalities in some studies, undue emphasis on early therapy could lead to unnecessary use of antibiotics and associated complications. For these reasons, the present guideline maintains its position to not recommend a specific time interval between diagnosis and antibiotic administration for patients. Reference: 1. Bordon J, e: al. Early administration of the first antimicrobials should be considered a marker of optimal care of patien's with community-acquired pneumonia rather than a predictor of outcomes. International Journal of Infectious Diseases 17 (2013) ¢293-e298. 2. Gattarello S etal. Improvement of antibiotic therapy and ICU survival ia ‘severe non-pnenmacoceal community ‘acquired pneumonia: a matched case-control studs Grtical Care (2015) 19:388. doi: 10.186/513084-015. FI. 3. Mandell, Lionel A et al. Infectious. Diseases Society of, America/Anerican Thoracic. Society Consensus Guidelines on the Management of Community-Aeguired Pneumonia in Adults, CID 2007; 44 (Suppl 2): 527-72. 4. Philippine Clinical Practice Guidelines on the Diagnosis, Empiric Management, and Prevention of Community acquired Pneumonia (CAP) in Immunocompetent Adults 2004 Update. 5. Simonetti A, et al. Timing of antibiotic administration and outcomes of hasnitalized natiems with cammuninie 2016 tpt, ‘What initial antibiotics are recommended for the empiric ‘treatment of community-acquired pneumonia’ + For low-risk CAP without comorbid illness, AMOXICILLIN remains the standard drug of choice. Use of extended macrolides may also be considered + For low-risk CAP with stable comorbid illness, f-lactam with f-lactamase inhibitor combinations (BLIC) or second generation cephalosporins with or without extended macrolides are recommended, For patients who have completed first-line treatment (BLIC or 2nd generation cephalosporin) with no response, an extensive work up should be done to identify the factors for failure of response. Work-up may include doing sputum Gram stain and culture, + For moderate-tisk CAP, a combination of an IV non antipseudomonal f-lactam —(BLIC, _ cephalosporin) with either an extended macrolide’ or a respiratory fluoroquinolone is recommended as initial antimicrobial ‘treatment, + For high-risk CAP without risk for Pseudomonas 4geruzinosa, a combination of an TV non-antipseudomonal Brlactam (BLIC, cephalosporin or carbapenem) with either an IV extended macrolide or an IV respiratory fluoroquinolone is recommended as an initial antimicrobial treatment. + For high-risk CAP with risk for P. aeruginosa, a combination of an IV antipneumococcal, antipseudomonal Brlactam (BLIC, cephalosporin or carbapenem) with an. extended macrolide and aminoglycoside OR a ‘combination of an IV antipneumococcal, antipseudomonal B-lactam (BLIC, cephalosporin or carbapenem) and an IV Ciprofloxacin or high dose IV levofloxacin.Wiha co mer es eas ‘Amoi Tl nding gh 17 = TD nie ted oi soso = sine SOD Most 0000 Ok Cte mp iek CAP en seco Amtinnattane | onc pm cence Heerteebtorne | Gumpipilpeone (BLO ag Mente oacpeet cae Somsieaimisone | lost melee Slot” | tex comempmeb Neue | Laem Comorin! gmbDoR eeenra. Sinn bon Senin na 8g Acitomin 00mg ODO ‘Citinyen tg Api Sin 15 ebro SE g1VOR Smee OD siege oo ea ens “Geum Ing ODOR “Km Smelgd =oa aoe oa etn mG cnocinceos ears seman momen aney References: Low Risk CAP: 1. Asadi Let al. Guideline adherence and macrolides reduced mortality in, ‘oupatients. with pneumonia, Respiratory Medicine (2012) 106, 451-458 2a cree cet meee ee ree told Commun cenied pretreat setenete reves and meta-analysis, Eur Respir J 2011; 37: 838-864. 4. Department of Health, Antimicrobio! Resistance Sutveillanse Program (RSP) 2014 Daa’ Summary Be al einen, AMSPoc20201 4e20Summary*e20Reportpae lccessed on: 13 June 2013 oa Laopaiboon M et al. Azithromycin for acute lower respiratory” tract" infections Review) Cochrane Batuhase Sys ew 2078 Mar 8 Issue 3: CDO01954. do 10-1003/13031838 CDM01954 put Llor C et al, Efficacy of high doses of oral penicillin versus amoxicillin in the treatment of adults with non Severe pneumonia attended in the, community: study protocol for a randomised controlled ria. BMIC Family Practice 2013, 14:50, Pathale Set al. Antibiotics for community-acquired pneumonia in lt outpatients: Cochrane Database Syst Rev 2014 Ocr 9:10. CD002100. doi: 10.1002/14031838. Cd 602109 pubs. Petitpretz P et al. Oral Moxfloxacin vs High-Dosage Amoticili in the Treatment of Mildéto- ‘Moderate Comminity-lequired, Spected." Pneumococcal Preumontain Adults, CHEST 8004; 119:185- 199, Moderate Risk CAP: i Asadi Let al. Macrolide-Based Regimens and Mortality in’ Hospitalized Patients With Community-Acquired Pneunonia: A Systematic: Review and Meta-analysis, Clinical Infectious Diseases 2012:55(3):371-80 Eliakim-Raz Net al. Empiric antibiotic coverage of ‘atypical pathogens for community-acquired pneumonia in hospitalized adults (Review) Cochrane Database Syst Rev 2012, Issue 9:CDOO4AIS, dol: 10: 1002/14651838, CD004478 pubs File TM Jr et al, Integrated analysis of FOCUS 1 and FOCUS 2: “randomized, doubled-blinded, multicenter Phase 3 ‘vials of the efficacy and safety of cefiaroline {fosamil versus ceftriaxone in patients with community ‘acquired pneumonia. Clin Infect Dis 2010; 51:1395-405, Gilbert D et al. The Sanford Guide 10 Antimicrobial Therapy 4ath Edition. Kuzman I et al. Efficacy and safety of moxifloxacin in community acquired pneumonia: “a prospect ‘multicenter, observational study (CAPRIV)..- BMC Pulmonary Medicine 2014, 14:108.10. u. 18 1 Lee JH et al. High-dose levofloxacin in community- ‘acquired pneumonia: randomized, open-label stud Clinica Drug Investigation. 2012; 32(9) 569-576 Mandell, Lionel A et al. Infectious Diseases Society of America/American Thoracie Society Consensus Guidelines ‘on the Management of Community-Aequired Pneumonia fm Adis, C1D 207,84 (Suppl 2): 827-72 MeFarlane A et al. The Value of Macrolide-Based Regimens for Community-Aeguired Pneumonia. Curr Infect Dis Rep, 2015 Dec:17(12):80. Mukhae H et al. Efficacy and safety of levofloxacin in patients with bacterial pneumonia evaluated according fo the ney" “Clinical ‘Evaluation Methods for’ New Animicrobial Agents. to Treat Respiratory Infections {Second Feion- fect Chemother 2014 ul: 2007417 O’brink-Haws K et al. Moxifioxacin Pharmacokinetic Profile and Efficacy Evaluation in Empirie Treaument of Community Acquired Pneumonia Antimicrobial Agents and Chemetherapy April 2018 Volume’ $9 Number 4: 2398-2405, Postma DE et al. Antibiotic Treatmem Strategies for Community-Aegnired Pneumonia in Adults N Engl J Med 2015372131223 Raz-Pastewr A etal. Fluoroguinolones or macrolides alone versus combined with f-lactams for adults with community ‘acquired pnrumonia: Systematic review andmetacanalysts. Int Antinisod Agents 2013 Sep40(3): 242-8 Rodrigo C et al. Single versus combination antibiotic therapy in adults hospitalised vith community acquired pneiononia, Thora 2013 May:68(5):493-5, Tamm M et al. Clinical and bacteriological outcomes in hospitalised patients with community-acquired pneumonia treated with acthromycin plus eefriaxone, or eefriaxone plus. claritiromycin or erythromycin: a prospective, randomised. multicentre studs. Clinical Microbiology and Infection. 2007; 13(2):162-171 16. Vv, 18, essmer A etal. Impact of intravenous b-lactam/macrolide versus blactam monotherapy on mortality in hospitalized patients with commurity-acquired pneumonia. Journal of Antimicrobial Chemotherapy (2008) 63, 1025-1033, Ye X et ak Improvement in clinical and economic ‘outcomes “with "empiric antibiodc. therapy covering ‘typical pathogens for community-acguired pneumonia ‘patienis: a multicenter cohort study International Journal Of Infections Diseases 2018 Mar 24;40°102-107 Zhao X et al._A randomized contalted clinical trial of Tevoftoxacin 750 mg versus 500 mg intravenous Infusion in he treatment of community-acquired pneumonia. Diagn Microbiol Infect Dis 2014 Oct;S0(2):141-7. Zhong NS et al. Ceftarolin fosamil versus ceftriaxone for the Haber of datum pralionds wilh comrade pneumonia: a randomised, contrlted, double-blind, phase 3, noninferiority with nested superiority tal. Lancet Infect Dis. 2015 Feb:15(2):161-71 High Risk CaP: 1 Adrie etal, Initial use ofone or two antibiotics forertically iil patients with communityacquired pneumonia impact (on survival and bacterial resistance. Critical Care 2013, 17 (6):R26S. dot: 10.1186ce1 3095. Adamantia Let al. Managing CAP in the ICU. Curr Infect Dis Rep. 2015 Nov:1710):48. Kamata K et al, Clinical evaluation of the need for carbapenems 10 treat community acquired and healtheare- associated pneumonia. J Infect Chemother 21 (2015) So6e603, Liu, Catherine etal. Clinical Practice Guidelines by the Infectious Diseases Society of America for the Treatment of Methicilin-Resistant Staphylococcus Aureus Infections tn Adults and Children. Clinical Infectious Diseases 2011;1-38. Mandell, Lionel A et al. Infectious Diseases Society of America/ American Thoracte Society Consensus Guidelines‘on the Management of Community-Acquired Pneumonia in Aduis. CID 2007;44 (Suppl 2): 827-72 Meters, ML et al. Epidemiology, microbiology, and treatment considerations for bacterial pneumonia complicating influenza International Journal of Infectious Diseases 16 (2012) e321-e331 Paul M et al, Beta lactam antibiotic monotherapy versus feta lactam aminoglycoside antibiotic combination therap? for sepsis (Review), Cochrane Database Syst Rev. 2014 Jan 7:1:CDO03344, dol: 10.1002/14651838. (CD 003344. pub3. Sibila O et al. Risk factors and antibiotic therapy in Paeruginosa community-acquired pneumonia. Respirology. 2015 May:20(4):660-6 Key Points to Remember For Low Risk CAP ‘The advantage of using some extended macrolides over ‘amoxicilin on Sireptococeus pneumoniae isthe once-a-day Sosazing of azalide. The 2014 repors 4.3% erythromyein resistance for Sireprococcus pneumoniae If the patent has history of allergy to Pelactam drugs (ew. amoxil, may opt fo use an extended macrolide ‘The increase in the dosage recommendation of amoxicillin was based on the 2014 ARSP report that shows consistent level of resistance of Streptococcus pnewmoniae to penicillin, ‘whether using meningeal breakpoints 10.3%. US Food and Drug Administration (FDA) warmed. the public that azithromycin can eause abnormal changes in the leetrcsl activity of the heart that may Tead to a potentially Total inegular heart rhythm. Patients at particular risk for developing this condition include those "with known risk factors such as existing QT interval profongation, low blood levels of potassium or magnesium, a slower than normal Jneart rat, or use of certain drugs used to treat abnormal heart ‘hgthans oe setts, been associated with increased risk of high baseline risk, bat not for younger Azithromycin use 24 hours 2. Less cough and resolution of respiratory distress (Gormalization of respiratory rae) 3. Improving white blood eell count, no bacteremia 4. Hologic agents not a high-risk (virwlenresistant) pathogen eg. Legionela, S. aureus or Gram: ‘egative enere baci 5. No unstable comorbid conton or fiethrestening Omplicton. such as myocardial infaet Congestive art flr, complete her block, new Stal Abraton,suprventcolr achycani, ee 6. No sign of organ dysfunction such as hypotension, ‘cute mental changes, BUN to creatinine Tato of 10:1, hypoxemia, and metabolic acidosis ation is clinically hydrated, taking oral ids and is le to take oral medications + The choice of oral antibiotics, following inital penieral therapy s based on available cata results Aimicrobial spectrum, efficacy, safety and cost. In eneral, when switching to oral antibiotics, either the Same agent asthe parenteral antibiotic or an antibiotic from the same drug elass shouldbe used.DOSAGE OF ORAL AGENTS. FOR STREAMLINING OR SWITCH THERAPY 625 ng TD oF gn BID 00mg 0D a mH =0mg6D 2w mew BD 500 750mg0D [a0omgoo Sulaniciin [750 mg B1D ai Reference: 1. Ramirez JA. Clinical stability and switch therapy in hhasptalised patients with community-acguired pneumonia: ‘arewe there yet? Eur Respir J 2013; 41" 5-6 How long is the duration of treatment for CAP? + Duration of treatment is S 10 7 days for tow Fisk uncomplicated bcterial pneumonia. (Strong recommendation, Moderate to Very Low Quality of Evidence NICE guidelines 2014) ‘+ Treatment duration for moderate rsk bacterial pneumonia is 7-10 days (Strong recommendation, Low Quality of Bvidence, NICE guidelines 2014) + For moderaterisk and high-risk CAP or for those with ‘suspected or confitmed Gram-negative, S. aureus or P ‘aeruginosa pneumonia, treatment should be prolonged to Pa iene acid been ane ‘+A treatment regimen of 10 to 14 days is recommended for Micoplasma and Chlamsdophile poeumonia while egionelia pneumonia is treated for 14 t0 21 days +A S-day course of oral or LV therapy for low-risk CAP and «10-day course of 1V for Legionella pneumonia is possible ‘with new agents such as the azalides, which possess long halflife and achieve high tissue levels that prolong its duration oFefec. ‘+ Patients should be afebrile for 48 to 72 hours with no signs ‘of clinical instability before discontinuation of treatment. ‘TABLE 4, DURATION OF ANTIBIOTIC USE BASED ON ETIOLOGY Most bacterial peumonis [5-7 days fetes Gra sept ive pathogens S.auret | 3.5 (rales) for S. paeumoniae (ABSA and Sa) and | Cate SS pe eran ae Gps ‘and MRSA), and Pare 'MSSA community aequred ays bs Bactereic = Tonge up 12 days MRSA community: acquired Crominteremic-7.21 days i Rcereme ener up 10 28 ays Pseudomonas aeruginosa fa non-bacteemic= 14-21 days bb eteremie longer up 1 28 days sod 10 Clamp if Tegionela Reference: TF 10 wali 1. Aliberti, Stefano et al. Duration of Antibiotic Therapy in Hospitalied Patients with Community-acguired Pneumonia, Bur Respir J 2010; 36: 1281342. Aliberti, Stefano et al. How to Choose the Duration of “Antibiotic Therapy in Patients with Pneumonia. Current (Opinion April 2015; 28 (2). 177-184. 4. Chowdhury Get al. Sever-day antiboti. courses ord eer pec a pepe epee mais Clin Mero inet. 17 210) pp. 188.1858 4. Lim, WS. BTS guidelines for the management of Toa 3008: GtaT 8s coe 136th SOB. H434 S. Lim, WS et al. British Thoracie: Society community ‘acquired pneumonia guideline and the NICE pneumonia ‘guideline: how they fit together. Thorax 2015,0:1-3, dois 10.11 $0/thoraxjni-2015-200881 6. National Institue for Health and Care Excellence (NICE) Pneumonia ~ Diagnosis and management of Community ‘and Hospital-acquired Pneumonia in Adulis. December S014. 7. Niederman, Michael. Comnunity-acguired Pneumonia, Ann Intern Med. 2013,163(.1TC1. doi:10.73267 AITC2015100603, 8. Pinzone R etal. Review Article Duration of Antimicrobial Therapy in Community Acquired Pneumonia: Less Is ‘More. The Sciemific World Journal Volume 2014: 1-8 9% Scalera NM, et al. Determining the duration of therapy for patients with community-acquired pneumonia. Curr Infect Dis Rep 2O15:15:1 91-5. 10, Stefano A et al. How to choose the duration of antibiotic Uherapy in patient with preumonaa. Cure Opinion Infect Dis 2015, 28: 177-84. + The clini history, phyicl examination andthe rns fall avalbe vetgaons shuld be veel The Paint should be reassessed for posible resistance to Ihe anibiots feng given or forthe presence of ber pathogens such as. Af. ercilosi, ise, prsies Sr fmt ne soa th e vised asd fo culture rn + Follow-up chest radiograph is recommended to investigate for ether conditions such as pneumothorax, cavitation and extension t previously uninvolved lobes, pleural eflusion, pulmonary edema and ARDS. For an underlying mass, bronchiectasis, loculation , pulmonary abscesses, a CT scan would provide more information ‘+ Obtaining additional specimens for microbiologic testing should be considered, TABLE 5. REASONS FOR A LACK OF RESPONSE TO "TREATMENT OF CAP. What should be done for patients who are not improving after ‘72 hours of empirie antibiotic therapy’? + The lack of a response to seemingly appropriate treatment ina patient with CAP should lead toa complete reappraisal, rather than simply to selection of alternative antibaties, Fe References Musher DM et af . Community-Acquired Pneumonia N Engl J Med 2014:371-1619-28.2 Welte Tet al. Managing CAP patients at risk of elinical fare. Respiratory Medicine 2015;100-187-169, ‘When can a hospitalized patient with CAP be discharged? + Inthe absence of any unstable coexisting illness or other Iifethreatening complication, the patient may bedlischarged ‘once clinially stable and oral therapy is initiated, + Arepeat chest radiograph prior to hospital discharge is not needed ina patient who is clinically improving. + A repeat chest radiograph is recommended during a follow-up visit, approximately 4 to 6 weeks after hospital discharge to calablish «new radiographic baseline and ty exchide the possibility of malignaney associated with, ‘CAP, particularly in older smokers. ‘Table 6, Recommended hospital discharge criteria, ‘Dring the 24 hours before dlacharge, the patient should have the following characteristes (unless this represents the baseline status) i 1 Temperature of 3637.50 i 2- Pale = 100mm i 3. Respaiory rate Between 1624imnute [4 Systolic BP =90 mig Blood oxygen saturation OO 6 Functioning gastointestinal act Reference: 1. AlibertiS etal. Crieriaforetnical stabi in hospitalized ‘Patients with community-acquired penmonia Eur Respir 2013; 42: 742-749, 2. Robinson Set al. Patient Outcomes on Day 4 of Intravenous Antibiotic Therapy in Non Intensive Care Unit Hospiatized Adults With Community-Aeguired Bacterial Pneumonia. Infectious Diseases. in Clinical Practice November 2014; 22: 320-325, What other information should be explained and discussed ‘with the patient? Explain to patients with CAP that afer sarting treatmer sympioms are expected to steadily improve, although the ‘improvement will vary with the severity ofthe pneumonia, Most people ean expect tha by week: fever should have resolved 44 weeks: chest pain and sputum production should have substantially reduced 6 weeks: cough and breathlessness should have substantially reduced 3 months: most symptonss should have resolved but fatigue may sil be present {6 months: most people will feel back to normal Reference 1. Alibert§ PeyraniP Filardo G Minacidi M Amir A Blasi F Ramirez JA. Association between time to clinical stability and outcomes after discharge in hospitalize tients with communityacquirel pneumonia. Chest BOL sug’ 140 (2) 4828 2. EL Moussaoui R etal. Long-term symptom recovery and health-related quality of life in patients with mild-to~ 'moderate-severe community-acquited pneumonia: Chest. 2006; 130¢4): 1168-1172, 4. National institute for Heath and Care Excellence (NICE) Preumonia = Disgnoss and management of Comm dnd Homptal acquired Pnewmonia ils. December Soi‘Community-nequired Pneumonia Task Force 2016 Chaie- Manolito L. Chua, MD, FPSMID Co-Chair Mari Rose A. De Los Reyes, MD, FPSMID Members: Remedies F. Coronel, MD, FPSMID Benilda B. Galvez, MD, FPCP, FPCCP ‘Alice Genuino, MD, FPAFP ‘Ryan Jeanne Cervo, MD, PAF Anna Guia Limpoco, MD, FPAFP (Claudette Mangahas, MD, FPCP, FRCP Leonardo Joseph Obusan, MD, FPCR. Ma Belle R.Siasoco, MD, FPCP, FPCCP. Ronigene M, Solantc, MD, FPCP, FPSMID Ma. Lourdes A. Villa, MD, FPCP, FPSMID ‘Advisers- Mary Ann D. Lansang, MD, FPCP, FPSMID (Chair, PSMID Standards of Care Committee) Meiadora C, Saniel, MD, FPSP, FPSMID, FIDSA (Chai, DOH NagComm)