Community Respiratory Tract Infections: Upper and Lower Thomas M - - PowerPoint PPT Presentation

Community Respiratory Tract Infections: Upper and Lower

Thomas M File, Jr MD MSc MACP FIDSA FCCP

Chair, Infectious Disease Division Summa Health System Akron, Ohio; Professor of Internal Medicine,Chair ID Section Northeast Ohio Medical University Rootstown, Ohio

Acute Respiratory Tract Infections

• Most common reason for antimicrobials
• Many infections

Unspecified URI Otitis Common Cold Acute Bronchitis Sinusitis Chronic Bronchitis Pharyngitis Pneumonia

• Challenge
• What infections warrant antimicrobial therapy?
• What etiology (viral vs bacterial)?

Which of the following options is the most

appropriate therapy for a 45 year old, non- smoking male with 5 days of non-productive cough, malaise, and nasal obstruction who is afebrile with normal vital signs and whose lungs findings are clear to auscultation?

• A. Macrolide antimicrobial
• b. Fluoroquinolone antimicrobial
• c. Doxycyline antimicrobial
• d. Telithromycin
• e. non of the above

Appropriate Use of Antibiotics: Indications for RTI

• Consider most likely pathogens
• Stratify patients according to risks for resistant

strains and predictors of outcome

• Recent Antibiotic use
• Severity of illness

Campbell GD Jr, Silberman R. Clin Infect Dis. 1998;26:1188.

Risk Factors for Drug-Resistant

• S. pneumoniae
• Recent

antimicrobials

• Recently hospitalized

patients

• Extremes of age

(especially < 6 yrs)

• Day care center
• Underlying disease
• HIV
• Immunodeficiency
• Institutionalized

patients

You are asked to evaluate a 20 y/o college student who presents with a sore throat of 2 days duration. Afebrile. Pharynx-moderate erythema. Which of the following options is your choice of management ?

• A. Pen VK 500 mg bid x 10 days
• b. Oral cephalosporin Qd x 5 days
• c. Z-pac
• d. Rapid antigen test for S. pyogenes
• e. Throat culture

Pharyngitis

• Most pharyngitis is viral
• S. pyogenes (GAS)—only common etiology of pharyngitis

for which antimicrobials are indicated

• accounts for up to 25% in children, much less in adults
• Concern for severe post-streptococcal complications
• Acute rheumatic fever (risk is low in developed countries)
• Acute glomerulonephritis (no evidence ATB prevents)
• Local suppurative (low risk)
• Other causes: GC, Mono, Mycoplasma, Grp C/G Strep,

Arcanobacterium hemolyticus (unresponsive to PCN), Fusobacterium necrophorum (Lemierres syndrome)

Inf Dis Soc Am Guidelines, Clin Inf Dis. 2012: available www.idsociety .org

Rash associated with Arcanbacterium hemolyticus

Pharyngitis

• Indications for antimicrobial therapy
• Base on rapid antigen test or throat culture
• Newer antigen tests have sensitivity approx 90%
• No need to do culture for adults if antigen neg.
• vs syndromic approach (adenopathy, exudate,

fever, lack of cough….)

• Low predictability
• Consider if high risk; ie, history of recurrent GAS-pharyngitis or ARF;

epidemic)

Inf Dis Soc Am Guidelines, Clin Inf Dis. 2012: available www.idsociety .org .

Grp A Strep vs Viral Pharyngitis Grp A Strep Viral

Inf Dis Soc Am Guidelines, Clin Inf Dis. 2012: available www.idsociety .org .

IDSA Guideline: Grp A Strep therapy

Inf Dis Soc Am Guidelines, Clin Inf Dis. 2012: available www.idsociety .org

• b. Avoid if immediate PCN hypersensitivity; c. Resistance variable

Centor R. Annals Intern Med. 2009; 151: 812-815 (Dec 1)

• F necrophorum casues pharyngitis in adolescents/young adults as common as

Grp A Strep

• Use a penicillin or cephalosporin or clindamycin (not macrolide) if a

consideration in Strept-negative pharyngitis

• Pharyngitis normally resolves in 3-5 days
• 2 major flags are worsening sore throat and neck swelling
• Often bacteremic and toxic; may require surgical intevention

Which of the following is most appropriate concerning management of sinusitis?

• A. The most common cause of acute rhinosinusitis is

pneumococcus b. An imaging study (X-ray or CT) is recommended to identify acute maxillary sinusitis c. Clinical manifestations of illness reliably predict the etiology d. An antimicrobial can be warranted if symptoms of sinusitis are persisting for > 10 days e. The drug of choice of mild bacterial sinustis is a macrolide

Management of Sinusitis

• Acute sinusitis is generally viral
• 0.5%-2% develop secondary bacterial sinusitis
• Predictors of bacterial sinusitis (acute maxillary)
• Symptoms >7 days; severe
• Facial pain/tenderness, fever, dental pain, abnormal

transillumination, intranasal pus, unresponsive to decongestants

• Imaging studies not suggested for initial Rx
• Most common bacterial pathogens: S. pneumoniae, H.

influenzae

Sinus and Allergy Health Partnership. Otolaryngol Head Neck Surg. 2004;130(Suppl 1):1-45.

Pathophysiology of Bacterial Sinusitis

–

Viral URI most common preceding cause

Adapted from Gwaltney: Clin Infect Dis 23:1209-1225, 1996; Reilly: Otoloaryngol Head Neck Surg 103:856-862, 1990.

Radiologic Imaging: CT

Photo courtesy J. Hadley, MD.

Antimicrobial Therapy for Acute Bacterial Rhinosinusitis

• Mild severity, no recent antibiotic
• Amoxicillin, amoxicillin/clavulanate, cefpodoxime, cefuroxime,

(Alternative: TMP/SMX, doxycycline, or macrolide)

• Mild, recent antibiotic
• Amoxicillin/clavulanate (high-dose), amoxicillin (high-dose),

cefpodoxime, cefuroxime, respiratory FQ (if -lactam allergic)

• Moderate severity, no recent antibiotic
• Amoxicillin, amoxicillin/clavulanate, cefpodoxime, cefuroxime, new

FQ (if -lactam allergic)

• Moderate, recent antibiotic
• New FQ, amoxicillin/clavulanate (high-dose), combination

(amoxicillin or clindamycin + cefixime)

Sinus and Allergy Health Partnership. Otolaryngol Head Neck Surg. 2004;130(Suppl1):1-45.

Augmentin XR™

• Pharmacokinetic design
• Bilayer tablets with immediate release layer of amoxicillin and

clavulanate, and extended release layer of amoxicillin

• Each tablet contains 1 gm amox and 62.5 gm clavulanate
• Increases daily dose of amoxicillin—2000 mg BID = 4000 mg/day
• Maintains daily dose of clavulanate—125 mg BID = 250 mg/day
• Extends coverage to include S. pneumoniae with elevated

amoxicillin MICs

• Indications
• CAP; Acute Bacterial Sinusitis; especially nWhen PRSP is a concern
• Tolerability
• Similar to Augmentin 875 (clavulanate dose is the same)
• Diarrhea approx 10% (most are mild)

New Guideline Recommendations (pending review and approval)

The following clinical criteria (any of three) are recommended for identifying patients with acute bacterial vs. viral rhinosinusitis:

• Onset with persistent symptoms (nasal discharge of any quality or

daytime cough or both) lasting for >10 days without any evidence of clinical improvement);

• Onset with severe symptoms (purulent nasal discharge and fever or

facial pain) lasting for at least 3-4 days at the beginning of illness; or

• Onset with initial improvement followed by worsening of respiratory

symptoms (nasal discharge or cough or new onset fever or headache) lasting for 3-4 days. Clin Infect Dis. April, 2012

New Recommendations (pending approval)

• Amoxicillin-clavulanate rather than amoxicillin alone is

recommended as empiric antimicrobial therapy for ABRS in both children and adults.

• It is recommended that “high-dose” amoxicillin-clavulanate be

administered to children and adults from geographic regions with high endemic rates of penicillin-nonsusceptible S. pneumoniae, severe infection, a recent history (within 3 months) of hospitalization or antibiotic use, or those with co- morbidities or are immuno-compromised.

• Either doxycycline (not suitable for children) or a respiratory

fluoroquinolones (levofloxacin or moxifloxacin) are recommended as alternative agents for empiric initial antimicrobial therapy in patients allergic to penicillin. (macrolides or SXT/TMP NOT listed)

• The recommended duration of therapy for uncomplicated

ABRS in adults is 5-7 days. (Children 10-14d)

New Recommendations

New Recommendations

• Intranasal saline irrigations are recommended as an

adjunctive treatment in patients with ABRS. Either physiologic

• r hypertonic saline is recommended.
• Intranasal corticosteroids may be used as an adjunct to

antibiotics in the empiric treatment of ABRS, particularly in those with a history of allergic rhinitis. This recommendation places a relatively high value on a small additional relief of symptoms and a relatively low value on avoiding increased resource cost.

• Neither topical nor oral decongestants and/or anti-histamines

are recommended as adjunctive treatment in patients with ABRS (in placebo trials no significant benefit and causes increase in inflammation)

COPD

Airflow limitation/

• bstruction present

AECB

• Increased dyspnea
• Increased sputum volume
• Increased sputum purulence

Bronchiectasis Emphysema

Chronic bronchitis

• Chronic productive cough for 3 months

in each of 2 successive years

• 85% of COPD

COPD = chronic obstructive pulmonary disease; AECB = acute exacerbations of chronic bronchitis

McCrory et al. Chest. 2001 Apr;119(4):1190-209

Which of the following options is most appropriate concerning management of acute exacerbation of chronic bronchitis (AECB)?

A. Antimicrobials should be given to a patient with chronic bronchitis who has an increase of dyspnea B. The most common cause is S. pneumoniae C. Sputum culture is recommended for patients with uncomplicated, mild AECB D. Amoxicillin/clavulante is an option for therapy of patients with complicated AECB

AECB: Etiology

• Role of bacteria—debated but considered leading cause
• Manifestations not differentiating

(bacterial vs nonbacterial)

• ABECB
• Core pathogens: H influenzae, S pneumoniae, M

catarrhalis

• Complicated: Enterobacteriaceae
• Severe: Pseudomonas spp, others
• Role of atypicals—debated, Chlamydia

Microbial Infection Impaired Lung Defences Tissue Damage Inflammation

A vicious cycle of infection and inflammation in AECB

Cole and Wilson

Acute Bacterial Exacerbations of Chronic Bronchitis (AECB)

• Chronic Bronchitis
• Sputum prod 3 months, 2 consecutive years
• AECB: Increased Sputum volume,Purulence, Dyspnea
• 50% of AECB are bacterial in etiology
• Clinical manifestations of bacterial vs nonbacterial etiology

indistinguishable

• Stratification based on
• Type of exacerbation (I, II, III)
• Treat if Type I (all three symptoms); Prob Type II (includes

purulence)*

• Risk factors: Number of AECBs, comorbidity, FEV1, steroid use,

recent antibiotics

*Anthonisen NR et al. Ann Intern Med.

1987;106:196

Guidelines for management of AECB

Balter MS, et al. Can Respir J. 2003;10(Suppl B):3B-32B.

< 4 exacerbations/yr No comorbid illness FEV1 >50% >4 exacerbations/yr Cardiac disease FEV1 <50% Home O2 Chronic oral steroids Ab use in past 3 mo As in group II FEV1 usually <35% Multiple risk factors

• H. influenzae
• H. Spp
• M. catarrhalis
• S. pneumoniae

Group I plus Klebsiella spp + Other gram-negatives Increased -lactam resistance Group II plus

• P. Aeruginosa &

Multi-resistant Enterobacteriaceae

I, Chronic bronchitis w/o

risk factors (Simple) II, Chronic bronchitis w Risk factors (Complicated) III, Chronic suppurative bronchitis

< 4 exacerbations/yr No comorbid illness FEV1 >50% >4 exacerbations/yr Cardiac disease FEV1 <50% Home O2 Chronic oral steroids Ab use in past 3 mo As in group II FEV1 usually <35% Multiple risk factors 2nd generation macrolide 2nd/3rd cephalosporin, Amoxicillin Doxycycline Trimeth/sulfameth Fluoroquinolone -lactam/-lactamase inhibitor Tailor to pathogen Ciprofloxacin

I, Chronic bronchitis w/o

risk factors (Simple) II, Chronic bronchitis w Risk factors (Complicated)

III, Chronic suppurative bronchitis

Guidelines for management of AECB

Balter MS, et al. Can Respir J. 2003;10(Suppl B):3B-32B.

Community-acquired Pneumonia (CAP)

• Leading cause of morbidity and mortality
• 40,000 deaths/year in US
• Esp. elderly and patients with comorbidities
• No. I cause due to infection
• Incidence
• General pop.: 1−12/1000/year
• > 65 years: 25−44/1000/year
• 5-6 million cases/year
• Approx. 1 million admissions/year (40% one year mortality; Kaplan et
• al. Arch Intern Med 2003; 163: 317-323)
• > 75% treated as outpatients
• Cost of treating CAP exceeds $17 billion/year
• Performance Measures

File T. Lancet 2003; File and Tan JAMA 2005 File T and Marrie T Postgrad Med. 2010

Types and Spectrum of Pneumonia

Craven D. Curr Opin Infect Dis. 2006;19:153-160.

Morbidity and Mortality

Risk of MDR Pathogens

Community-

acquired

pneumonia (CAP)

Hospital-acquired pneumonia (HAP)/ ventilator- acquired pneumonia (VAP)

Healthcare- associated pneumonia (HCAP)

Which of the following patients is/are included in the classification of Healthcare-associated pneumonia?

a. 34 y/o hospital employee, previously healthy, admitted for acute pneumonia b. 56 y/o male admitted for CHF who is noted to have pneumonia on the day after admission c. 76 y/o bedridden male transferred from a nursing home for acute pneumonia d. All above e. None of above

HCAP : Now a Part of Nosocomial Pneumonia Guidelines

• Inclusion of healthcare related pneumonia
• Hospitalized in the preceding 90 days
• Nursing home/extended care facility residence
• Home infusion therapy (including antibiotics)
• Chronic dialysis
• Home wound care
• Family member with multidrug-resistant pathogen
• Treat for MDR pathogens, regardless of when

in hospital stay pneumonia begins

Am J Respir Crit Care Med. 2005;171:388-416.

Community-acquired pneumonia (CAP): Case

• 26 Y/O FEMALE
• Healthy
• Headache, Fever,

Nonproductive Cough for 7 days

• T-100.80 F; P-100; RR-24;

Ausc-Bilateral hi-pitched rhonchi

• O2 sat-98% Room Air
• SHOULD SHE BE

ADMITTED?

• What antimicrobial(s)

Site of Care Decision

• Determines
• Cost of care
• Intensity of diagnostic testing
• Empiric choice of antibiotics
• Advantages of outpatient therapy
• Cost
• Patient preference
• Faster convalescence and avoidance of nosocomial

complications

• Science and Art
• Mortality prediction rules (PSI, CURB-65)
• Social circumstances
• Co-existing conditions

Pneumonia Prediction Rule for Mortality Risk Assessment

STEP 1 STEP 2

No No

Class I

No Yes Yes Yes

Class III

(71–90 points)

Class IV

(91–130 points)

Class V

(>130 points)

Class II

(70 points)

Fine MJ, et al. N Engl J Med. 1997;336:243-50.

Assign points for: Demographic variables Comorbid conditions Physical observations Laboratory and radiographic findings Is the patient >50 years of age? Does the patient have any of the following coexisting conditions: Neoplastic disease; congestive heart failure; cerebrovascular disease; renal disease; liver disease Does the patient have any of the following abnormalities: Altered mental status; pulse 125/min; respiratory rate 30/min; systolic blood pressure <90 mm Hg; temperature <35ºC

• r 40ºC

Prediction Rule Step 2: Algorithm

Pt Characteristic Points

Age

• No. of years (-10 for female)

Cancer 30 Liver disease 20 CHF, CVD, Renal disease 10 RR >30/min, SBP <90 mmHg, Confusion 20 Temp <35ºC, >50ºC 15 Pulse, beats/min 10 BUN; Sodium <130 mmol/l 20 Glucose >250 mg/dl; Hct < 30% 10 pO2 < 60 mmHg 10

Prediction Rule: Risk Categories

Total Points Class Mortality % How to Treat I 0.1 Outpatient  70 II 0.6 Outpatient 71-90 III 0.9-2.8 Brief hospital

• bservation

91-130 IV 8.2-9.3 Inpatient >130 V 27.0-29.2 Inpatient ICU

Risk categories according to two validation cohorts (38,039 inpatients and 2287 in- and outpatients)

Fine MJ, et al. N Engl J Med. 1997;336:243-50.

Applying the CURB-65 Rule

Lim WS, et al. Thorax. 2003;58:377-82.

Likely suitable for home treatment Consider hospital supervised treatment Options may include: Short stay inpatient; Hospital-supervised

• utpatient

Manage in hospital as severe pneumonia Assess for ICU admission especially if CURB-65 score = 4 or 5 CURB-65 Score Treatment Options

0 or 1 2 3 +

Group 1 Mortality Low (1.5%) (n=324, died=5) Group 2 Mortality Intermediate (9.2%) (n=184, died=17) Group 3 Mortality High (22%) (n=210, died=47)

Any of: Confusion* Urea >7 mmol/l Respiratory Rate ≥30/min Blood pressure (SBP <90 mmHg or DBP ≤60 mm Hg) Age ≥65 years

CAP: Diagnostic Considerations

• Microbiologic studies
• Standard Culture methods (sput, blood)

– Limitations (infrequently identify etioloty)

• Gram stain, Urinary Antigens

– pneumococus, legionella

• Newer Molecular tests (e.g., PCR)

– Potential for more rapid diagnosis – Allows rapid pathogen-directed therapy

• Biomarkers (Procalcitonin)
• Differentiate Bacterial vs virus

CAP: EMPIRICAL THERAPY Principles

• TREAT EARLY
• TREAT MOST LIKELY PATHOGENS
• S. pneumoniae (?Drug resistance*); H. influenzae
• Atypicals—studies in North America show high

prevalence (even though may not be severe, therapy reduces illness)

• Others (local epidemiology)
• Cannot differentiate etiology based on initial findings

*Recent ATB (Following of ? Relevance: Recent Hospitalization; DayCare; Multiple comorbidities; Age)

Most Common Etiologies of CAP

Ambulatory Patients Hospitalized (non-ICU)† Severe (ICU)†

• S. pneumoniae
• S. pneumoniae
• S. pneumoniae
• M. pneumoniae
• M. pneumoniae
• S. aureus
• H. influenzae
• C. pneumoniae

Legionella spp.

• C. pneumoniae
• H. influenzae

Gram-negative bacilli Respiratory viruses†† Legionella spp.

• H. influenzae

Aspiration Respiratory viruses‡

Based on collective data from recent studies; †Excluding Pneumocystis spp.

‡ Influenza A and B, adenovirus, respiratory syncytial virus, parainfluenza

File TM. Lancet. 2003;362:1991-2001.

Healthy Outpatient Outpatient at Risk for DRSP* Inpatient, non- ICU Inpatient, ICU†

Macrolide OR Doxycycline Respiratory fluoroquinolone OR Beta-lactam plus macrolide Respiratory fluoroquinolone OR Beta-lactam plus macrolide Beta-lactam plus azithromycin OR Beta-lactam plus fluoroquinolone

*Includes healthy patients in regions with high rates of macrolide resistance.

†Treatment of Pseudomonas or MRSA is the main reason to modify standard therapy for ICU

patients.

Mandell L, et al. Clin Infect Dis. 2007;44(Suppl 2):S27-S72.

Empiric Therapy in CAP: IDSA/ATS

ICU = intensive care unit

45

Antimicrobial Recommendations:

Outpatient Treatment

• Previously healthy and no use of antimicrobials within 3

months:

• A macrolide (Strong recommendation, level I evidence)
• Doxycycline (Weak recommendation, level III evidence)
• Presence of comorbidities or antimicrobials within 3 months
• Respiratory fluoroquinolone (moxi, gemi, levo [750 mg]) (Strong

recommendation, level I evidence)

• Beta lactam PLUS a macrolide (Strong recommendation, level I

evidence)

• If high rate of “high-level” macrolide-resistant S. pneumoniae,

consider use of alternative agents listed above (Moderate recommendation, Level III evidence) Mandell L, et al. Clin Infect Dis. 2007;44 (Suppl 2):S27-72.

Clinical Infectious Diseases 2010; 51(2):189–194

Community-acquired pneumonia (CAP): Case

• 66 Y/O MALE
• Smoke, Diabetes, CHF
• Treated with macrolide for

‘sinusitis’ 8 weeks ago

• Headache, Fever, Cough

for 3 days, New Confusion

• T-101.80 F; P-110; RR-28;

Ausc-rhonchi RLL

• O2 sat-92% Room Air
• SHOULD HE BE

ADMITTED?

• WHAT ANTIMICROBIAL

CXR courtesy of T. File MD

CAP: Joint Commission/CMS Performance Measures for Inpatients 2012

• Blood culturesa

― For all ICU patients;a optional for general ward patients ― Prior to antibiotics if obtained in emergency departmenta

• Empiric antimicrobials according to guidelinesa

― Exceptions: pathogen-directed therapy, clinical trials,

diagnostic uncertainty

• Timely administration of antibiotics (6 h; 2008)b
• Measurement of blood gases or pulse oximetryc
• Pneumococcal and influenza vaccined
• Smoking-cessation counseling
• CAP mortality (July 2008)
• 30-d readmission rate for pneumoniae (2013)

a2012 Core Measure bRetired as CAP measure cRetired 2009 dNow global measure eComplements Core

Measures as part of the Hospital Readmissions Reduction Program— hospitals with higher than expected 30-d readmission rates for AMI, heart failure and pneumonia and will incur penalties against their total Medicare payments beginning in FFY 2013.

Centers for Medicare and Medicaid Services and the Joint Commission. Specifications manual for national hospital inpatient quality measures. Available at: www.jointcommission.org/specifications_manual_for_national_ hospital_inpatient_quality_measures.aspx. Accessed June 6, 2012. File TM et al. Clin Infect Dis. 2011;53(Suppl 1):S15-S22.

IDSA/ATS Recommendations

Inpatients, non-ICU Treatment

Respiratory fluoroquinolone (moxi 400 mg, levo 750 mg) (Strong recommendation, level I evidence) Beta-lactam (ceftriaxone, cefotaxime, amp/sulb, ertapenem) PLUS a macrolide (Strong recommendation, level I evidence)

Mandell L, et al. Clin Infect Dis. 2007;44 (Suppl 2):S27-72.

New antimicrobials with CABP indication: Tigecycline Ceftaroline

CAP CASE:

Assuming this patient does not have bronchiectasis or advanced COPD, which of the following regimens is NOT recommended in the IDSA/ATS guidelines and is considered in variance with the CMS Performance Indicator?

• A. Moxifloxacin
• B. Cefriaxone plus azithromycin
• C. Piperacillin/tazobactam plus azithromycin
• D. Ampicillin/sulbactam plus azithromycin
• E. Levofloxacin

CAP CASE:

Assuming this patient does not have bronchiectasis or advanced COPD, which of the following regimens is NOT recommended in the IDSA/ATS guidelines and is considered in variance with the CMS Performance Indicator?

• A. Moxifloxacin
• B. Cefriaxone plus azithromycin
• C. Piperacillin/tazobactam plus azithromycin
• D. Ampicillin/sulbactam plus azithromycin
• E. Levofloxacin

Antimicrobial Recommendations

Inpatients, non-ICU Treatment

Respiratory fluoroquinolone (moxi 400 mg, levo 750 mg) (Strong recommendation, level I evidence) Beta-lactam (ceftriaxone, cefotaxime, amp/sulb, ertapenem) PLUS a macrolide (Strong recommendation, level I evidence)

Mandell L, et al. Clin Infect Dis. 2007;44 (Suppl 2):S27- 72.

CAP Recommendations

Inpatients, ICU Treatment

• A beta-lactam (cefotaxime, ceftriaxone,

ampicillin-sulbactam) PLUS either azithromycin (level II evidence) OR a respiratory fluoroquinolone (level I evidence)

• (For penicillin-allergic patients, a respiratory

fluoroquinolone and aztreonam are recommended) (Strong recommendation)

Mandell L, et al. Clin Infect Dis. 2007;44 (Suppl 2):S27-72.

New Antimicrobials for Serious CAP

• Tigecycline (Tygacil) IV
• Glycylcycline (derivative of minocycline)-broad spectrum

including S. pneumoniae, atypicals

• Approved for Intra-Abd, Bacterial Skin Infections, CAP

(non ICU)

• CAP- Comparable to levofloxacin1
• HAP/VAP –Comparable to imipenem for HAP; Inferior for VAP2
• Listed as option for CAP admitted to general ward
• 100mg initially, then 50 mg Q 12h;
• Adverse effects-N/V
• Ceftaroline (Teflaro ) IV
• 600 mg q 12 h
• 1. Tanaseanu et al. Diag Microbiol Infect Dis. 2008; 61: 329-38; 2. Maroko et al. ICAAC 2007 L-

730

• 1200+ patients; Ave age—61 years; all PORT III or IV
• Clinical Cure for S. pneumoniae:

Ceftaroline 59/69 (85.5%); Ceftriaxone 48/70 (68.6%)

Ceftaroline has greater affinity for PBP 2x

File T et al. Clin Infect Dis. 2010; 51: 1395-1405

Recommendations-IDSA/ATS 2007: ICU

• A beta-lactam (cefotaxime, ceftriaxone, ampicillin-

sulbactam) PLUS either azithromycin (level II evidence) OR a respiratory fluoroquinolone (level I evidence)

• (For penicillin-allergic patients, a respiratory

fluoroquinolone and aztreonam are recommended) (Strong recommendation)

• Special considerations
• Pseudomonas (bronchiectasis, steroids….)
• CA-MRSA (recent influenza…..)

*Infectious Diseases Society of America; Ameriacn Thoracic Society Communityacquired Guidelines. Mandell L, et al. Clin Infect Dis. 2007;44 (Suppl 2):S27-72.

Case of Severe Community-acquired Pneumonia

• 30 y/o female presents to ER at

0400 with respiratory distress;

• immediate intubation
• History of ILI (Influenza-like illness)
• Gram stain reveals Gram + cocci

clusters (Staph)

• Vancomycin added
• Patient has multi-organ

dysfunction; expires at 1600

• CA- MRSA (community-associated

methicillin-resistant S. aureus) isolated

CXR courtesy of T File MD.

CAP Case: Assuming he was treated with ceftriaxone +

azithromycin and it is now Day 3-Afebrile, other VS stable, alert, no unstable comorbidity; O2 sat-96%; sputum culture obtained on admission + for S. pneumoniae ( PCN susceptible). What is your course of action?

• A. Change to po amoxicillin discharge on next day
• B. Change to po fluoroquinolone and discharge

now

• C. Change to po amoxicillin and discharge now
• D. Continue IV ATB
• E. Add IV Vancomycin

SWITCH THERAPY (IV to po) and DISCHARGE CRITERIA

• Switch Therapy
• When good clinical response, comobidities stabilized, can

take po

• If pathogen identified, ‘Directed’ Therapy
• If empiric, can utilize ‘negative’ lab results to simplify

therapy (e.g. if urinary antigen and blood cultures negative)

• Discharge
• If VS and O2 status stable, and no unresolved

comorbidities, can discharge at time of oral switch

• No value to observe in hospital for 24 h after switch
• (Dunn et al. Am J Med. 1999; 106:6)

CAP Case: How long do you treat?

• A. 5-7 days
• B. 7-10 days
• C. 10-14 days
• D. 14-21 days

Short- vs Long-course Therapy for CAP

• Usual dose: 7–14 days
• Time to stability
• 3 days (Halm et al. Arch Intern Med 2002)
• 4 days (Menendez et al. CID 2004)
• Meta-analysis (≤ 7 days vs longer)

Conclusion: No difference in efficacy and safety

Dimopoulos 2008, p1848; Drugs; 2008: 68: 1841-54

CAP: Duration of Therapy

Immunocompetent Host

File and Niederman. Inf Dis Clinics NA 2004 IDSA/ATS Guidelines 2007

• Based on available data
• Minimum of 5 days if afebrile by 48-72 hrs for

‘core pathogens’

• Longer for other pathogens or evidence of

extrapulmonary infection

• S. aureus, Pseudomonas
• Shorter course Therapy
• Reduced resistance, AE, cost

Community RTIs Take home messages

• Pharyngitis: Base therapy on antigen test

(check susceptibility if erythromycin used)

• Sinusitis: New clinical guidelines; use

antimicrobials only if warranted; amox/clav 1st line therapy; saline irrigation

• Pneumonia: Stratify by risk factors; Newer

molecular tests; treat 5 days if good response by 3 days.

Respiratory Tract Infections: Prevention

• Smoking cessation
• Vaccines
• Pneumococcal
• Influenza
• Reducing effect of comorbidities*
• Controlling CHF, Hyperglycemia (higher mortality)
• Reducing swallowing disorders etc.
• Brushing teeth
• Pandemic Preparation

(www.hhs.gov/pandemicflu/)

*File and Tan JAMA 2005; 294: 2760-63.