Pneumonia Guidelines: A Changing...

• Michael S. Niederman , M.D., F.C.C.P

• Clinical Director Associate ChiefDivision of Pulmonary and Critical Care Medicine

• New York Presbyterian Hospital/Weill Cornell Medical Center

• Professor of Clinical MedicineWeill Cornell Medical College

[email protected]

Pneumonia Guidelines: A Changing Landscape

FINANCIAL DISCLOSURE

• Dr. Niederman is a consultant for:

– Bayer, Pfizer, Merck , N8 Medical, Shionogi, Paratek, and Astra Zeneca

– He has received research grants from:

Bayer, Merck and Shionogi

Imaging Diagnosis of CAP To Guide When To Treat

• 2251 patients treated for CAP in EPIC study

– 2185 with radiographic pn on CXR

– 66 with CT only pneumonia

• 748 had CT

– 652 with x ray pneumonia

– 30 with negative CT and + CXR

– 66 with CT only pneumonia

• Upchurch CP et al. Chest 2018; 153:601-10

• Editorial and algorithm

• Niederman , M. Chest 2018; 153:583-85

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North American CAP Guidelines

• Development of guidelines– Canadian guidelines 1993

– ATS 1993

– IDSA 1998

– CDC 2000

– Canadian (Pulm/ID) guidelines 2000

– IDSA guidelines 2000

– ATS guidelines 2001

– IDSA update 2003

– ATS/IDSA Joint Guideline 2007

Modifiers Affecting Bacteriology: 2007 Guidelines

• DRSP– Age > 65 years, ß-lactam therapy within 3 months,

alcoholism, immune suppression (including steroids), multiple medical co-morbidities, exposure to child in day care

• Enteric Gram-negatives– Nursing home residence, underlying cardiopulmonary

disease, multiple medical co-morbidities, recent antibiotic therapy

• Pseudomonas aeruginosa– Structural lung disease (bronchiectasis), corticosteroids

(> 10 mg prednisone/day), broad-spectrum antibiotics for > 7 days within the past month, malnutrition

Community-acquired Pneumonia:Empiric Therapy– ATS/IDSA 2007

Outpatient

Previously well: Advanced Macrolide; Doxy

CoMorbidity or recent ATB use*:

Resp Fluoroquinolone (Levofloxacin750 mg or

Moxifloxacin 400 mg) ;

High dose Beta-lactam** + (macrolide or doxycyline);

Ceftriaxone + macrolide or doxycycline

*Base decision on ‘prior antimicrobial used’; use alternate

**Amox 1 gm TID; Amox/clav 2 gm BID preferred: alternatives: cefpodoxime, cefuroxime (500 mg BID)

Mandell LA et al. Clin Infect Dis 2007;44 Suppl 2:S27-72

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Community-acquired PneumoniaEmpiric Therapy – ATS/IDSA 2007

Inpatient – general ward

• Respiratory fluoroquinolone (levofloxacin 750 mg/day, moxifloxacin 400 mg/day)

» OR

• β-lactam PLUS macrolide/doxycycline

– (preferred agents include: cefotaxime, ceftriaxone, amp/sulbactam; consider ertapenem in selected patients)

– Cefepime, imipenem, meropenem, piperacillin/tazobactamonly if pseudomonal risks present

(For carefully selected patients without risk factors for DRSP or GNR, monotherapy with azithromycin can be considered)

Consider ‘Other pathogens’ based on epidemiology


Therapy of Severe CAP: ATS /IDSA 2007 Regimens

• No Pseudomonal Risk Factors

– Selected Beta –lactam(cefotaxime, ceftriaxone, ertapenem )PLUS

• IV MacrolideOR

• IV Quinolone

• Pseudomonal Risk Factors Present

– Selected Beta-lactam(cefepime, piperacillin/tazobactam, imipenem, meropenem)PLUSCiprofloxacin or High Dose Levofloxacin (750 mg)

– Selected Beta-lactamPLUS AminoglycosidePLUS

• IV macrolide OR

• IV anti-pneumococcal quinolone

Pseudomonas aeruginosa risk factors: Structural lung disease (bronchiectasis), corticosteroids (> 10 mg prednisone/day), broad-spectrum antibiotics for > 7 days within the past month, malnutrition

CONSIDER MRSA THERAPY IN SELECTED PATIENTS , ESP POST INFLUENZA

Do Not Withhold Antibiotics Just Because You Document Viral Infection

• Retrospective cohort study of 117 SCAP (all in ICU) patients in Singapore (84 with identified pathogens)

• 92.3% intubated

– Isolated viral (27.4%), pure bacterial (29.1%), mixed viral and bacterial ( 15.4%). DX eval inclPCR on EA

– Pneumococcus and Influenza A most common

– Mixed with OR of 13.99 for mortality

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Multivariate mortality risk: PCT level, APACHE II and

mixed infection Quah J, et al. BMC Infect Dis

2018;18:451

Relevant Issues For New CAP Guidelines

• Cardiac Disease and Monitoring/ Site of Care

• HCAP: What Now??

– Pseudomonal and MDR risk factors

• Macrolides and their benefits

• New antibiotic therapies

• Therapy of CA-MRSA

• Biomarkers and Duration of Therapy

• Steroids for severe CAP

• Vaccines

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• Vaccines

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Cardiac Disease Complicating Severe Pneumococcal CAP

• Up to 30% with CAP experience major adverse cardiac event in hospital up to 10 years post CAP, adding to mortality

• Non human primate model of pneumococcal pneumonia to see if organisms enter myocardium and cause cardiomyocytenecroptosis

• 6 with pneumonia (3 treated),3 controls

• Organisms in myocardium of all pneumonia animals and all with myocardial necroptosis and apoptosis

• Stain for RIP 3 (measure of necroptosis) in cardiac tissue of untreated and recovering animals. This led to new myocardial fibrosis.

– Necroptosis increased after antibiotic treatment .

– ? As source of late cardiac events, along with scarring

– Reyes LF et al. AJRCCM 2017; 196:609-20

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Cardiac Disease Complicating Severe Pneumococcal CAP

– Reyes LF et al. AJRCCM 2017; 196:609-20

– Myocardial organism entry

– Necroptosis of cardiac cells

– Collagen Formation

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Criteria for Severe CAP: 2007 IDSA/ATS Guidelines

• Maybe OTHER MINOR CRITERIA

• Hyponatremia– On admit: 28% of 342 CAP

patients with hyponatremia ( < 136 mEq/L). 4.1% < 130 mEq/L.• Hyponatremia on admit with

increased mortality and increased length of stay

• 10.5% developed in hospital, unrelated to severity of illness on admit.

• Nair, Niederman, et al: Am J 2007; 27:184-190.

• Thrombocytosis . Thrombocytosis (>400 K) added to mortality (OR 2.7), but biphasic relationship, with low platelets ( < 100 K) also a risk. – Prina E, et al. Chest 2013;143:767-

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• Abnormal arterial CO2. Higher mortality with hypocapnia (13.4%) and hypercapnia (20%) vs, normal (5.3%).– Laserna E, et al. Chest 2012;

142:1193-1199

Need 1 MAJOR or 3 MINOR


PCT and CAP Outcome

Huang DT, et al. Ann Emerg Med 2008; 52: 48-58.










• Vaccines

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Risk Factors for MDR Pathogens: APPLY TO ALL PNEUMONIA PATIENTS

Definitions and Patients Included

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A SIMPLIFIED AND UNIFIED ALGORITHM FOR ALL ADMITTED PNEUMONIA PATIENTS

Severe Illness

Assess Severity of Illness (ICU or mechanical ventilation) and

MDR Risks (recent antibiotic therapy, poor functional status, recent hospitalization,

in hospital for at least 5 days, hemodialysis, immune suppression)

YESNO

Pneumonia Is Present and Patient Hospitalized n=1089(CAP n=656 , HCAP n=638, HAP n=140, VAP n=55)

Maruyama et al. Clin Infect Dis 2019; 68: 1080-88

> 1 MDR Risks:n=104

Anti-pseudomonal beta-

lactam PLUS quinolone

Or Aminoglycoside PLUS

Optional vancomycin or

Linezolid

0–1 MDR Risks:n=721

Treat for common CAP

pathogens with:

Quinolone,

β-lactam/Macrolide

0 MDR Risks:n=31

Therapy

with β-lactam

PLUS Macrolide or

Quinolone

> 2 MDR Risks:n=233

Anti-pseudomonal beta-

lactam PLUS quinolone

Or Aminoglycoside PLUS

Optional vancomycin or

Linezolid

A SIMPLIFIED AND UNIFIED ALGORITHM FOR ALL ADMITTED PNEUMONIA PATIENTS

• 82.5% were treated according to the algorithm

– 4.3% got inappropriate therapy with the algorithm

• MDR in : VAP (50.9%), HAP (27.9%), HCAP (10.9%) and CAP (5.2%).

• With ≥2 MDR risks vs 0-1 risk, saw MDR pathogens more often : 25.8% vs 5.3%, p< 0.001.

• 30-day mortality rates : VAP (18.2%), HAP (13.6%), HCAP (6.7%) and CAP (4.7

– Lower with 0–1 MDR risks than with ≥2 MDR risks (4.5% vs. 12.5%, p<0.001).

• MDR risks and inappropriate therapy but NOT type of pneumonia predict mortality in multivariate model

• Maruyama et al. Clin Infect Dis 2019; 68: 1080-88

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What Happened When Algorithm was NOT Followed?

• 82.5% followed algorithm and 4.3% got inappropriate therapy

• For the 17.5% (191 patients) NOT following algorithm

– 3.7% inappropriate therapy , BUT

– 74 got narrower therapy than algorithm recommended and 7 (9.5%) got inappropriate therapy

– 117 got broader spectrum than recommended and no inappropriate therapy

• Initial treatment failure rates were higher than inappropriate therapy. Thus failue NOT always related to therapy choice

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• Vaccines

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Adjunctive Macrolide Therapy in Non-Severe CAP: CAP-START Study

• Cluster-randomized trial: 4 months each of beta-lactam alone (n=656), BL-M (n=739), quinolone (n=888). Random order among 6

hospitals.

• Shorter duration and earlier oral therapy with FQ

• Lower mortality (9.0%,8.8% vs 11.1%) with BL and quinolone vs. BL-M. No regimen sig better, but meet NI criteria for BL vs. BL-M.

– Atypical pathogens in 2.1%

– 38.7% in BL group got atypical coverage

– 25% in all groups with NO radiographic confirmed CAP

– Lower adherence to BL-M strategy

– Low severity: median CURB-65 of 1, EXCLUDED ICU patients

– 131/2299 patients in PSI class V. No mortality diff between

groups in PSI V patients.

– Postma DF et al. NEJM 2015; 372:1312-23

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Randomized Trial of BL/M vs. BL Montherapy in CAP

• Open label, multicenter trial with 580 patients (moderately severe)

• Beta-lactam/macrolide vs. Beta-lactam alone (add macrolide for proven Legionella)

• Primary endpoint : Time to clinical stability (HR, BP, Temp, RR, Oxygenation)

• Non-inferiority of monorx NOT proven for CS (66.4 % vs. 58.8%, day 7 , CS for combo vs mono)

• Combination best if atypical pathogen or more ill (PSI IV)

• Garin N, et al. JAMA Intern Med 2014; 174:1894-1901

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Routine Macrolide Use In Severe CAP?

• Meta-analysis of macrolide use in severe CAP

• 28 studies, nearly 10,000 patients

• Mortality risk of 0.82 with macrolide (21% vs 24% (p=0.02)

• Higher benefit if risk adjusted

• Trend of BL/M being better than BL/F

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Sligl W, et al. Crit Care Med 2014; 42:420-32

Conclusions for Adding Macrolide Therapy To a Beta-Lactam in CAP

• In patients with mild CAP or a low likelihood of atypical pathogen infection, macrolide benefits may be small

• If severe CAP, and severe pneumococcal bacteremia

– Macrolide addition to a beta-lactam reduces mortality

• Benefit may be due more to anti-inflammatory effects rather than to anti-microbial effects

• Multiple anti-inflammatory effects of macrolides

• Benefit applies even if add to quinolone

• Benefit applies for macrolide resistant organisms

• Benefit in VAP due to gram-negatives without eradicating the pathogen

• Additive benefit to adjunctive corticosteroids

• Future: develop new macrolides with primarily anti-inflammatory properties, rather than anti-bacterial

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• Vaccines

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New Antibiotics for Pneumonia

• CAP

– Solithromycin

– Quinolones: avarofloxacin, nemonoxacin, zabofloxacin, delafloxacin

– Omadacycline

– Eravacycline

– Lefamulin

• Vincent JL, et al. Crit Care 2016; 20:133










• Vaccines

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Is Empiric MRSA Therapy Needed in All ICU-Admitted CAP?

• 621 with ICU admitted CAP in CAPO study

– 57 treated emprically for MRSA (vancomycin or linezolid)

– MRSA rx group sicker

– 20 proven MRSA, 35% mortality. 10 treated empirically. Same outcome empiric vs. late rx.

• No difference in-hospital mortality (25%), 28 day mortality, LOS , time to clinical stability with empiric MRSA rx.

• Griffin AT, et al. Infection 2012; DOI 10.1007/s15010-012-0363-1

Differences Between CA-MRSA Pneumonia and MRSA in the HCAP Patient

• Distinguish CA-MRSA in previously healthy patients, from MRSA arising in the community in patients with HCAP risks. CA-MRSA

uncommon and often post influenza or viral illness

– Wunderink R. Inf Dis Clin North Am 2013; 27:177-188

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Clinical Features of CA-MRSA: Need a High Level of Suspicion

• Often a serious illness , with necrotizing pneumonia, but not always. Usually in previously healthy patient.

– Wunderink R. Inf Dis Clin North Am 2013; 27:177-188

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CT Scan of CA-MRSA Patient on Admission

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PVL Positive S. Aureus Pneumonia: Role of Methicillin Resistance and Proper Therapy

• 133 with PVL positive Staphylococcal CAP

– 29 MRSA

– 104 MSSA

• 39% mortality, Methicillin resistance NOT a mortality predictor.

• 64% mechan vent. Hemoptysis assoc. with mortality.

• 33.7% got antitoxin (linezolid, clindamycin or rifampin), with reduced mortality (6.1% vs. 52.3%, p < 0.001)

• Sicot N, et al. Clin Microbiol Infect 2012; 19: E142-148

Conclusions About CA-MRSA Pneumonia Therapy

• CA-MRSA pneumonia should be distinguished from MRSA in the community arising in HCAP patients

• Often necrotizing, but does not always need ICU care

– Associated with toxin production (so is MSSA)

• Slow to resolve

• Not all severe CAP patients need empiric MRSA therapy

• Optimal therapy unclear

– Role of toxin inhibition

– Therapy of pneumonia with bacteremia: drugs for bacteremia may not penetrate lung well or work on pneumonia: vancomycin and daptomycin

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• Vaccines

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Admission PCT To Guide The Use of Antibiotics in Radiographic CAP : Pro CAP

• 302 patients with radiographic CAP randomized to PCT guided vs. standard rx

• Rx: <0.1 strongly discouraged, <0.25 discouraged, > 0.25 encouraged, > 0.5 mcg/L strongly encouraged

• Measure PCT on admit, 6-24 hours (if withheld), day 4,6,8.

• 28% with PCT <0.25 and 15% in PCT group had withheld abtc.; 1% withheld without PCT data

• Christ-Crain M, et al: Am J Respir Crit Care Med 2006; 174:84-93

Pro HOSP Study: Using PCT To Reduce Antibiotic Exposure in RTI’s

• Multicenter trial in 6 Swiss hospitals

• 1359 ED patients with LRTI randomized to PCT (n=671) guidance vs. standard care (n=688)

• 68% in each group with CAP, 17% AECB, 11%

acute bronchitis, 4% others

• PCT patients with CAP with shorter duration

therapy, fewer antibitoics, fewer antibiotic side effects

• Scheutz P,et al. JAMA 2009; 302:1059-66.

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Is Procalcitonin Valuable to Guide Antibiotic Use in CAP?

• Randomized trial in 14 hospitals to PCT data or not, for guiding antibiotic use in patients with LRTI (20% CAP)

• In all, only 62/808 in PCT group had levels >0.25

• Huang D, et al. NEJM 2018; 379:236-49

Getting to Short Duration By Protocol

• Randomized trial of 312 hospitalized CAP patients

• Guideline (intervention): minimum 5 days, afebrile for 48 hours, < 1 clinical instability factor, acurate empiric rx, no extrapulm infection

• Control: dictate duration by clinician

• Mean of 5 vs. 10 days. Same outcomes: clinical success and symptom resolution

• If planning short duration, do we need biomarkers?

• Uranga A, et al. JAMA 2016; 176: 1257-65

PCT Guidance of Therapy Duration in Dutch ICUs

• SAPS study in 15 Dutch hospitals

• Non-blinded: 761 PCT guided,

785 standard of care

– Stop if PCT decr 80% or <0.5 mcg/L

• PCT guidance led to less antibiotics, shorter dur rx, lower 28 day mortality

– Higher reinfection with PCT

– No diff in serial CRP measures

– No stop by PCT in half , esp if not stable

• deJong E, et al. Lancet Inf Dis 2016; on line

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• Vaccines

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Meta-Analysis of Steroids for CAP

• Randomized controlled trials of severe and non-severe CAP patients

• Possible reduction in mortality by 3% (in severe CAP) , need for MV by 5% and LOS by 1 day

• More hyperglycemia, not GI bleeding

• Siemieniuk RAC , et al. Ann Intern Med 2015; 163:519-528

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Steroids in Severe CAP To Reduce Treatment Failure

• Multicenter randomized trial of 0.5mg/kg methylprednisolone q12h x 5 days (n=61) vs. placebo (n-59). Rx within 36 hours.

• Severe CAP (70-80% in ICU) + elevated CRP > 150 mg/L on admit

• Less treatment failure (esp late and with radiographic progression) in steroid group

– No mortality difference.

• Torres et al. JAMA 2015; 313:677-86.

Corticosteroids may increase mortality in patients with influenza

pneumonia; maybe more hospital acquired infection, but data are weak

and conclusions are cautious

Cochrane Database of Systematic Reviews 2016, Issue 3. Art. No.: CD010406. DOI:

10.1002/14651858.CD0104

Select patients with criteria for severe CAP (IDSA/ATS guidelines)

Select the most appropriate empiric antibiotic therapy

Start corticosteroids as soon as possible

•0.5 mg/kg/12 h Methylprednisolone or equivalent, for 5 days*

Select patients with serum levels of C-reactive protein >15 mg/dL

•Discard Influenza A H1N1 pneumonia during influenza season

•Discard general contraindications for corticosteroid administration:

•Diabetes mellitus needing insulin treatment

•Major gastrointestinal bleeding within 3 months

*We recommend 5 days of treatment although the meta-

analysis of Nie et al recommends more than 5 days

Monitor CRP

daily

Steroids To Prevent Cardiac Complications (Acute MI) of CAP

• 758 CAP patients, 241 (32%) got steroids, many for COPD. 41.4% with COPD got steroids vs 26.9% without COPD– Not include ICU patients.33% steroid treated patients were in PSI IV and

V

• Fewer MIs (0.24 vs. 0.89 per 100 person days) in steroid treated patients

• HR for MI of 0.47 with steroids. Benefit in COPD population only.

• Cangemi R, et al. Ann ATS 2019; 16:91-98

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Steroids To Prevent Cardiac Complications (Acute MI) of CAP

• 758 CAP patients, 241 (32%) got steroids, many for COPD. 41.4% with COPD got steroids vs 26.9% without COPD– Not include ICU patients.33% steroid treated patients were in PSI IV and

V

• Fewer MIs (0.24 vs. 0.89 per 100 person days) in steroid treated patients

• HR for MI of 0.47 with steroids. Benefit in COPD population only.

• Cangemi R, et al. Ann ATS 2019; 16:91-98

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Adjunctive IgM Enhanced Immunoglobulin in CAP

• IgM enriched immunoglobulin preparation for severe CAP

• Randomized, double blind , placebo controlled

– 160 patients with SCAP on mechanical vent

• IgM enriched trimodulin, 42 mg IgM/kg/day x 5 days

• No difference in VFDs, mortality, time to ICU discharge

• Reduction in mortality and increase in VFDs in subgroups with high CRP, low IgM , or both

• Welte T, et al. Intensive Care Med 2018; 44:438-48

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• Vaccines

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Sequence of Pneumococcal Vaccine Administration

• Unlike with polysaccharide vaccines, PCV induces a T cell response, inducing a recall response on re-vaccination

• Randomize, double-blind study of 720 adults age 60-64

• 2 vaccines, 1 year apart: PCV 13 x2, PCV 13 then PPS 23, PPS 23 then PCV 13.

• PCV 13 is more immunogenic than PPS 23

• If PCV 13 given first, it augmented the response to common serotypes , when PPS 23 was given later

– Higher titers after PPS 23, for 6/12 common strains, if PCV 13 given before PPS 23 vs. PPS 23 alone

• If PPS 23 given before PCV 13, less effective for all 13 strains than if PCV 13 given alone

• Greenberg RN, et al. Vaccine 2014; 2364-74

Current ACIP Pneumococcal Vaccine Recommedations

• Immunecompromising conditions: HIV, CRI, nephrotic synd, leukemia, lymphoma,Hodgkin’s, myeloma, malignancy, solid organ transplant, long term steroids, radiation therapy, congenital or acquired immunedef

Medium Risk

High Risk

Low Risk

Differences Between ERS and IDSA/ATS

• Local microbiology differs

• No interest in VAC by ERS

• ERS endorses quantitative cultures

• ERS with higher threshold for using empiric MRSA therapy

• ERS prefers linezolid to vancomycin

• Duration of therapy longer for resistance in ERS guideline

• ERS with less focus on combination therapy and broad spectrum. IDSA/ATS with 95% coverage goal

• ERS not as enthusiastic about PCT for duration of rx

• ERS endorses SOD






– Cover MRSA if > 25% of SA in the ICU is MRSA






2016 IDSA/ATS Nosocomial Pneumonia Guidelines and MRSA

• Risk factors for MDR pathogens: prior antibiotics in last 90 days (MRSA risk), hospitalization for > 5 days before VAP (late onset), shock, ARDS, acute RRT, and in ICU with 10-20% SA as MRSA.

• HAP: MRSA risk if >20% of SA is MRSA; use linezolid or vancomycin (SR, LQE) ; low mortality risk and no MRSA risk (<10-20% SA as MRSA) should be rx for MSSA (penicillin, carbapenem, cephalosporin)

• VAP: MRSA rx with vancomycin or linezolid (SR/MQE)

• Cover MRSA if > 10-20% of S. aureus is MRSA

– If 25% of VAP is due to SA, and 10-20% have MRSA, then MRSA in 2.5-5% of VAP

Vancomycin vs. Linezolid for MRSA

• Vancomycin. Glycopeptide, disrupts cell wall/peptidoglycan synthesis

– Pros: low resistance rates, years of experience

– Cons: slow increase in MICs (w/i “sensitive” range); poor lung penetration (12% serum levels); slowly bactericidal; nephrotoxicity

• May overcome poor penetration by synergy with rifampin

• Linezolid

– Pros: good lung penetration; IV/oral available; high bioavailability orally; no renal dose adjustment

– Cons: thrombocytopenia, optic neuritis, lactic acidosis (prolonged therapy); drug interactions (serotonin syndrome)

• Pletz MW , et al. Eur J Med Res 2010; 15:507-13

Vancomycin vs. Linezolid: Meta-Analysis with New Study Data

• Kalil et al. included new data with mortality in ITT (many without MRSA) as primary

endpoint. 9 randomized trials .

– Included 623 from Wunderink study in mortality analysis , but only 448 had MRSA, 415 completed rx. Argued in text vs. Wunderink data

• Concluded no difference in mortality, clinical response, micro response, renal failure

thrombocytopenia. More GI side effects with linezolid. .

• Trend to benefit in better studies: randomized, double blind

• Kalil AC et al. BMJ Open 2013; 3:e003912

PP

populat.

Meta Analysis of Clinical Response in documented MRSA pneumonia : Wunderink et al. BMJ 2014

Antibiotic Duration in IDSA/ATS Nosocomial Pneumonia Guideline 2016

• 7 day course of therapy for VAP (SR)

• Dose antibiotics by PK/PD data (WR)

–Continuous or prolonged infusion of beta-lactams

• Use PCT to add to clinical assessment to define duration of therapy (WR)

• IDSA/ATS; CID 2016

Using Pk/PD Principles DID NOT Reduce VAP Therapy Duration

• 227 patients in prospective, randomized, double blind study of 7 days of 1 gram doripenem over 4 hours q 8h vs. 10 days of 1 gram imipenem over 1 hour q 8h

• 7 day therapy with sig less clinical cure and higher 28 day mortality, esp with P. aeruginosa

– Kollef et al. Crit Care 2012; 16:R 218

Settings Where Short Duration Therapy May Not Be Appropriate

ERS Guidelines, 2017

Antibiotic Recommendations in IDSA/ATS Nosocomial Pneumonia Guideline 2016

• Select therapy based on local guidelines and microbiology

• Treat all VAP for S. aureus, P. aeruginosa and other gram negatives (SR)

– MRSA only if risks, or in ICU with > 10-20% SA as MRSA (WR)

• Dual Pseudomonal therapy from 2 different classes in at risk patients and those in ICU with >10% resistance to preferred monotherapy (WR)

• For P. aeruginosa , combination therapy for septic shock (WR), otherwise monotherapy (if know susceptibility) (SR)

• Avoid aminoglycosides if an alternative exists (WR)

• IDSA/ATS; CID 2016

Montherapy vs. Combination Therapy and Mortality Risk

• Meta-regression analysis of mono vs. combin rx in 50 studies of serious infection

• Increased mortality with combination therapy if < 15% mortality risk with monotherapy

• Reduced mortality with combination therapy if > 25% mortality risk with monotherapy

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Kumar A, et al. Crit Care Med 2010;

38:1651-4

Therapy Algorithm for VAP : ERS Guidelines

HAP/VAP: ASSESS RISK FOR MORTALITY AND MDR PATHOGENS

Antibiotic Monotherapy:

ertapenem ,

ceftriaxone, cefotaxime

levofloxacin,moxifloxacin

Empiric Antibiotics for HAP/VAP 2017

LOW MDR and

LOW MORTALITY RISK *

HIGH MDR RISK and/or >15%

MORTALITY RISK

No Septic Shock Septic Shock

Single Gram -negative

agent (if active for >

90%GNB in the ICU)

+/- M RSA therapy

Dual Gram-Pseudomonal

coverage

+/- MRSA therapy

HAP/VAP: ASSESS RISK FOR MORTALITY AND MDR PATHOGENS

Antibiotic Monotherapy:

ertapenem,ceftriaxone, cefotaxime

levofloxacin,moxifloxacin

Empiric Antibiotics for HAP/VAP 2017

LOW MDR and

LOW MORTALITY RISK *

HIGH MDR RISK and/or >15%

MORTALITY RISK

No Septic Shock Septic Shock

Single Gram-negative

agent (if active for >

90%GNB in the ICU) +/- MRSA therapy

Dual Gram-Pseudomonal

coverage

+/- MRSA therapy

*Low risk for

mortality is defined as a <

15% chance of

dying, a mortality rate that has been

associated with better outcome

using

monotherapy than combination

therapy when

treating serious infection.

Kumar A, SafdarN, Kethireddy S,

et al.. Crit Care

Med2010;38:1651-

1664

Why Do We Need New ERS Guidelines?

• ATS/IDSA may lead to overuse of broad spectrum antibiotics

• 316 patients with ICUA HAP and VAP

• MDR in 34%,but nearly 90% with at least 1 risk

• Adherence to guideline was low (<40%) but 83% got appropriate empiric therapy

• Ekren PK et al. Am J Resp Crit Care Med 2018 ; 197:826-30

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A Canadian Pharmacist’s Critique of 2016 IDSA/ATS Guidelines

• “Despite greater nuance in identifying the risk of MDR pathogens, recommended empiric antimicrobial regimens are now uniformly more broad spectrum”

• “at least one antipseudomonal agent is now recommended…. regardless of patient-specific risk factors”

• “The rationale for recommending broader empiric coverage for patients without increased risk for MDR infection is not provided” (IS ARDS alone a risk for MDR?)

– Wu H, et al. CJHP 2017; 70: 251-52

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Question 1

• Healthcare Associated Pneumonia

– A. has the same outcome as CAP

– B. should always be treated the same as nosocomial pneumonia

– C. occurs in patients with healthcare contact prior to hospitalization

– D. has the same bacteriology as CAP

Question 2

• According to CAP guidelines, the correct duration of antibiotic therapy

• A. should always be 10 days

• B. is independent of clinical response

• C. Depends on duration of hospitalization

• D. Can be as short as 5 days

Question 3

• In the therapy of community acquired MRSA

– A. Most patients with the diagnosis have mild illness

– B. Necrotizing pneumonia with pleural effusions is common

– C. therapy should be with oxacillin

– D. Corticosteroid therapy should be used routinely

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Question 3

• In the therapy of community acquired MRSA

– A. Most patients with the diagnosis have mild illness

– B. Necrotizing pneumonia with pleural effusions is common

– C. therapy should be with oxacillin

– D. Corticosteroid therapy should be used routinely

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Question 4

• In the IDSA/ATS HAP guidelines of 2016

– A. MRSA therapy should always include clindamycin

– B. Aerosolized antibiotics should be a routine adjunct to therapy in all patients with VAP

– C. Duration of therapy should be for a minimum of 10 days

– D. Dual therapy may be needed for patients with MDR pathogen infection

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Question 4

• In the IDSA/ATS HAP guidelines of 2016

– A. MRSA therapy should always include clindamycin

– B. Aerosolized antibiotics should be a routine adjunct to therapy in all patients with VAP

– C. Duration of therapy should be for a minimum of 10 days

– D. Dual therapy may be needed for patients with MDR pathogen infection

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Question 5

• Pneumococcal vaccination

– A. should always be with 23 valentpolysaccharide prior to 13 valent conjugate vaccine

– B. Should be with the 13 valent conjugate vaccine alone, since vaccination with the 23 valent polysaccaride vaccine adds nothing

– C. Is more immunogenic with the conjugate vaccine than with the polysaccharide vaccine

– D. Can be fully effective after just one lifetime vaccination with the polysaccharide vaccine

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Question 5

• Pneumococcal vaccination

– A. should always be with 23 valentpolysaccharide prior to 13 valent conjugate vaccine

– B. Should be with the 13 valent conjugate vaccine alone, since vaccination with the 23 valent polysaccaride vaccine adds nothing

– C. Is more immunogenic with the conjugate vaccine than with the polysaccharide vaccine

– D. Can be fully effective after just one lifetime vaccination with the polysaccharide vaccine

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Pneumonia Guidelines: A Changing...

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