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.