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 or 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/

obstruction 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

or 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

observation

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

outpatient

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.