Transcript CDC Principles of Appropriate Antibiotic Use for Acute

Modern Management of
Respiratory Infections
Ralph Gonzales, MD, MSPH
Associate Professor of Medicine; Epidemiology & Biostatistics
University of California, San Francisco
August 16, 2006
General Approach
 Making the Diagnosis
 Excluding Serious Illness
 Do I need a Diagnostic Test?
 Determining Treatment
 Symptomatic Therapy
 Antimicrobial Therapy
 Communicating Prognosis
 When to Return for Evaluation
Management Principles for
Uncomplicated Acute Bronchitis
Bronchitis
-CDC; ACP; AAFP; IDSA… 2001
 “The evaluation of adults with acute cough
illness… should focus on ruling out serious
illness, particularly pneumonia”
 In healthy, nonelderly adults, pneumonia is
uncommon in the absence of vital sign
abnormalities or asymmetrical lung sounds, and
CXR is usually not indicated.
 When cough>3 weeks, CXR may be warranted in
absence of other known causes.
Gonzales et al, 2001
Acute Cough Illness
-Ruling Out Pneumonia
Fever
Chills
Tachypnea
Tachycardia
Hyperthermia
Dullness to Percussion
Crackles
Rhonchi
Egophany
Leukocytosis
Metlay et al,
Likelihood Ratio Ranges
LR +
LR 1.7-2.1
0.6-0.7
1.3-1.7
0.7-0.9
1.5-3.4
0.8
1.6-2.3
0.5-0.7
1.4-4.4
0.6-0.8
2.2-4.3
0.8-0.9
1.6-2.7
0.6-0.9
1.4-1.5
0.8-0.9
2.0-8.6
0.8-1.0
1.9-3.7
0.3-0.6
Pneumonia Post Test Probabilities
20
Cough, Fever, Tachycardia and Crackles
Cough + Nl Vital Signs
0
10
Dullness to Percussion
8
Crackles
6
Fever
8
Tachycardia
0
10
20
30
40
50
60
70
Probability of Pneumonia
PreTest Prob
Metlay et al.
80
90
100
When to consider zebras…
• Cough > 3 weeks and normal CXR
• Meds, asthma, GERD, postnasal drip,
pertussis
• Nocturnal Cough
• GERD/postnasal drip, cough-variant asthma,
CHF
Pertussis
…not just for children anymore
• DPT-related immunity wanes as early as 3
years… and absent after 10-12 years
• attack rates as high as 100%
• 10-15% adults seeking care for persistent
cough have evidence of pertussis
• No clinical features distinguish pertussis in
previously immunized adults
Pertussis
• Diagnosis
• Dacron nasopharyngeal swab or wash
• PCR is now standard… much better sensitivity than
culture or DFA
• Coordinate with public health dept
• Treatment
• Erythromycin, azithromycin or clarithromycin
• Probably won’t help cough duration, which can last 36 months
• Reasonable to provide empirical Abx treatment to
contacts with cough, and close contacts/household
members as prophylaxis.
Pertussis Boosters for
Adolescents
• Adolescents and adults believed to be
vectors of increasing pertussis incidence
in young children.
• DTaP and Tdap: FDA approval 2005
• Boostrix (GSK; age 10-18 yrs)
• Adacel (Sanofi Pasteur; age 11-64 yrs)
• ACIP/NIP Recommendations: 2006
• Single DTaP/Tdap instead of dT at age 11-18
Cough-Variant Asthma




Cough > 2-3 weeks
Lack of wheezing
Normal PFTs
Features
 Worse at night
 Worse with exercise/cold
 Diagnosis
 Improved symptoms with bronchodilator
 Positive methacholine challenge test
Acute Bronchitis
-Therapeutic Objectives
Symptoms
Cough
Pathophysiology
-bronchial RAD
-mucus production
-post-nasal drip
-acid reflux
Treatment
-bronchodilators
-decongestants
-sinus therapy
-H2B; PPI
-cough suppressants
Wheezing/SOB
-bronchial RAD
-bronchodilators
Resolution of Acute Bronchitis
Stott, BMJ 1976
100
No Antibiotic
% Patients
80
(+) Antibiotic
60
40
20
0
0
2
4
6
8
10
12
Days with cough
14
16
18
Uncomplicated Acute Bronchitis
-azithromycin vs. vitamin C (Lancet 2002;359;1648-54)
Return to Usual Activities
Acute Bronchitis:
-bronchial hyperresponsiveness
Airflow obstruction in acute bronchitis
without underlying lung disease
100
80
60
40
20
0
<=80
>80
FEV1, % predicted
Eur Resp J 1994;7:1239
Acute cough illness treatment
-bronchodilator treatment
Randomized, placebo controlled trials
Melbye
1991
bronchitis
73
fenoterol aerosol
Decrease symptoms
Improved FEV1
Hueston
1991
bronchitis
34
oral albuterol vs.
erythromycin
Decrease cough @ 1 week
(41% vs. 82%)
Hueston
1994
bronchitis
46
albuterol aerosol vs.
(placebo + erythro)
Decrease cough @ 1 week
(61% vs. 91%)
Littenberg
1996
nonspecific
cough
104 albuterol aerosol
No benefit
OTC Cough Therapies
-Cochrane Review, 2004
• Antitussives
• codeine: 2 trials; no differences
• dextromethorphan: 2 of 3 trials show benefit
• Expectorants (guaifenesin): 1 of 2 trials benefit
• Mucolytics: 1 trial inconsistent benefit
• Antihistamine-Decongestant Combinations
• 1 of 2 trials show benefit
• Dextro-salbutamol: reduced nocturnal cough only
Acute cough illness: evaluation
summary
Acute Cough Illness
with or w/o phlegm
Patient Characteristics
Vital Sign Abnormalities
Elderly
Immunosuppression
COPD or CHF
HR > 100 bpm
RR > 24 br/min, or
T > 38o C
PEx Findings
No
Yes
Is Influenza
Likely?
Yes
Consolidation, or
Pleural Effusion
No
No
Consider CXR
Positive
Treat Pneumonia
Negative
Treatment Options*
Yes
Acute Exacerbations of COPD
Ann Intern Med 2001;134:595-99
Assessing Severity of Exacerbation
worsening dyspnea
increased sputum purulence
increased sputum volume
“severe” = all 3 present
“moderate” = 2 of 3 present
“mild” = 1 finding + (recent URI; unexplained fever;
increased cough/wheeze; or 20% increase in RR or HR
from baseline)
AECB: Treatment Recs (1)
Ann Intern Med 2001;134:595-99
• All AECB
• CXR utility high among hospitalized and ED patients
with AECB; ? Role in outpatient setting.
• Inhaled bronchodilator therapy
• beta-2 agonist and anticholinergic equal in efficacy,
but anticholinergic have fewer/benign side effects
• Use 2nd bronchodilator class only after 1st is at
max dose
AECB: Treatment Recs (2)
Ann Intern Med 2001;134:595-99
• Moderate-severe AECB
• pulse steroids up to 2 weeks if not currently taking
• oxygen, with caution, in hypoxemic patients
• Severe AECB
• initial narrow-spectrum antibiotics
• no RCTs show superiority of broad-spectrum agents
• UPDATED MARCH 31, 2005
• Not recommended for AECB:
• mucolytic agents; chest physiotherapy; methylxanthine
bronchodilators
AECB
-Therapeutic Objectives
Symptoms
 Cough
Pathophysiology
Treatment
-bronchial RAD
-bronchodilators
-mucus production
-decongestants/sinus
-bronchial; post-nasal drip
-acid reflux
-H2B; PPI
-cough suppressants
 Wheezing/SOB -bronchial RAD
-inflammation
-? Bacterial infection
-bronchodilators
-oral steroids
-? antibiotics
-BiPAP
AECB
-Who’s at greatest risk for relapse?
Miravitlles et al.
Ischemic heart disease
Degree of dyspnea
# office visits previous year
Asthma Exacerbations and
Telithromycin Johnston SL, NEJM 2006;354:1632-4.
• N=278; age 18-55; 90% white; mod-severe exacerbation
• 1/3 oral steroids
Telith
Baseline asthma score
∆ asthma score
∆ peak exp flow
Nausea
Diarrhea
3.0
1.3
78 l/m
5%
10%
Placebo
2.8
1.0
67 l/m
0%
4%
P-value
0.004
0.28
0.01
0.09
No difference according to Chlamydia or Mycoplasma infection status…
The ERA of Clinical Trials Registry… must report all prespecified outcomes
Rhinosinusitis: Diagnosis (1)
“The clinical diagnosis of acute bacterial
rhinosinusitis should be reserved for…” [B]
(1) rhinosinusitis symptoms > 7 days
+
(2) purulent nasal secretions
+
(3) maxillary pain/tenderness in face/teeth
Rhinosinusitis: Diagnosis (2)
“…rarely some patients with acute bacterial
rhinosinusitis present with dramatic
symptoms of severe unilateral maxillary
pain, swelling and fever”
Bacterial Sinusitis? Tough Call
Cx (+) sinus aspirate
purulent sinus aspirate
CT scan (a)
Xray (b)
high clinical suspicion
sinus symptoms
0
20
40
60
80
Bacterial Sinusitis, %
(a) CT scan criteria of air-fluid level or complete opacification.
(b) Xray criteria of mucosal thickening, air-fluid level or complete opacification.
100
Rhinosinusitis: Rx Studies
Au t h o r
Patient
Selection
Lindbaek, 1996
clinical suspicion
+
CT Scan Dx
van Buchem
1997
Stalman, 1997
Bucher, 2003
Merenstein,
2005
An t i b i o t i c R x *
Placebo Rx*
amoxicillin;
penicillin V;
placebo
D10
86%
57%
clinical suspicion
+
Xray Dx
amoxicillin;
placebo
D14
83%
77%
clinical criteria
doxycycline;
placebo
D10
85%
85%
amox-clavulanate;
placebo
D14
75%
75%
amoxicillin;
placebo
D14
48%
37%
clinical criteria
(only 32% Sx > 7
days)
clinical criteria
(100% Sx > 7
days)
*Percent improved or cured
Treatment
Ar m s
Rhinosinusitis: Abx Rx
“Acute rhinosinusitis resolves without
antibiotic treatment in most cases” [A]
Antibiotic treatment should be reserved for
patients with moderately severe symptoms
who meet criteria for clinical diagnosis of
acute bacterial rhinosinusitis and for those
with severe symptoms…regardless of duration
of illness.
Acute Sinusitis
-Therapeutic Objectives
Symptoms
 Pain
Pathophysiology
-increased sinus pressure due
inflammation & obstruction
-if >7-10 days of Sx
- bacterial infection risk
 Congestion -increased mucus production
-infection; recurrent; allergic
Treatment
- sinus drainage
-nasal saline wash
-nasal decongestant
-NSAIDs
-Antibiotics
-oral decongestants
-nasal steroids
Pharyngitis: Diagnosis
• “Clinically screen all adult patients with
pharyngitis for the presence of 4 criteria:”
•
•
•
•
history of fever
tonsillar exudates
tender anterior cervical LAN
absence of cough
• “Do not test or treat patients with none or
only 1 of these criteria…”
Spectrum Bias in GAS Test
Sensitivity of RAT
Pediatrics
Adults
Centor Score
0
1
2
3
4
47
65
82
90*
90*
*groups combined in study
Peds Ref: Hall MC et al. Pediatrics 2004;114:182
Adult Ref: Dimatteo LA et al. Ann Emerg Med 2001;38:648
61*
61*
76
90
97
Pharyngitis: Abx Rx
• “Test patients with 2-4 criteria using a
rapid antigen test, and limit Abx to
patients with positive test results [D]”, OR
• “Test patients with 2 or 3 criteria, and
limit Abx to patients with positive test
results or patients with 4 criteria” [D], OR
• “Do not use any diagnostic tests, and limit
Abx to patients with 3 or 4 criteria [B]”
Streptococcal Pharyngitis
-Therapeutic Objectives
Symptoms
 sore throat
Pathophysiology
-inflammation
-infection
Treatment
-NSAIDs
-antibiotics
Prednisone for Pharyngitis (Bacterial)
-Kiderman A et al, Br J Gen Pract 2005;55:218.
-18-65 years; primary
care
-2+ Centor criteria
-50% Strep Cx +
-Oral Prednisone 60
mg for 1 or 2 days
Delayed Antibiotic
Prescriptions
 Systematic Review: approx 50% decrease
in antibiotic treatment
 Br J Gen Pract. 2003 Nov;53(496):871-7.
 Delayed Antibiotic Treatment of Otitis
media (AAP; AAFP)….
 Definition of AOM (ie. “definite AOM”):
 recent, usually abrupt, onset of sx and signs, AND
 presence of middle ear effusion, AND
 distinct tympanic erythema or otalgia
Management of AOM
Guideline (AAP;AAFP 2004)
Child Age 2 mo to 12 yrs with
uncomplicated AOM
Assess and Treat Pain
Age
< 6 mo
6 mo - 2 yr
Definite Diagnosis
Abx
Abx
Uncertain Diagnosis
Abx
Abx if severe illness (T>39 or severe
otalgia; else observe
>2 yr
Abx if severe; else observe Observe
AND
*Caregiver informed/agrees/monitors/returns; System in place for communication
observe
Observe 48-72 hr with
assurance and appropriate f/u
Abx
Amoxicillin 80-90 mg/kg/day; unless
T>39 C. or severe otalgia or treatment
failure, then amox/clavulanate
How to help patients say “no”
to antibiotics for viral ARIs




Illness labeling: use “chest cold”, not “bronchitis”
Validate illness severity; focus on symptom relief
Provide a contingency plan
Discuss downside of unnecessary antibiotic use
 risk of carriage/spread of antibiotic-resistant bacteria
 Patient-physician communication
 Explain the illness
 Spend “enough” time
 Treat with respect
Therapeutic Windows in ARI
Treatments
 Influenza
 GAS pharyngitis
 To prevent ARF
 Pertussis
2 days
2 days
10 days
7-10 days
CDC/ACP/AAFP/IDSA
-Antibiotic Principles for ARIs
•
•
•
•
Gonzales R, Bartlett JG, Besser RE, Cooper RJ, Hickner JH, Hoffman JR,
Sande MA. Principles of appropriate antibiotic use for treatment of
acute respiratory tract infections in adults: Background, Specific
Aims and Methods. Ann Intern Med 2001;134:479-86.
Cooper RJ, Hoffman JR, Bartlett JG, Besser RE, Gonzales R, Hickner JH,
Sande MA. Principles of appropriate antibiotic use for acute
pharyngitis in adults: background. Ann Intern Med 2001;134:509-17
Hickner JH, Bartlett JG, Besser RE, Gonzales R, Hoffman JR, Sande MA.
Principles of appropriate antibiotic use for acute rhinosinusitis in
adults: background. Ann Intern Med 2001;134:498-505.
Gonzales R, Bartlett JG, Besser RE, Cooper RJ, Hickner JH, Hoffman JR,
Sande MA. Principles of appropriate antibiotic use for treatment of
uncomplicated acute bronchitis: background. Ann Intern Med
2001;134:521-29.
Bronchitis References
• Stott NC, West RR. Randomised controlled trial of antibiotics in patients with cough
and purulent sputum. BMJ. 1976;2(6035):556-9.
• Melbye H, Kongerud J, Vorland L. Reversible airflow limitation in adults with
respiratory infection. Eur Respir J. 1994;7:1239-45.
• Gonzales R, Steiner JF, Lum A et al. Decreasing antibiotic use in ambulatory
practice: impact of a multidimensional intervention on the treatment of
uncomplicated acute bronchitis in adults. JAMA. 1999;281:1512-9.
• Evans AT, Husain S, Durairaj L, et al. Azithromycin for acute bronchitis: a
randomised, double-blind, controlled trial. Lancet. 2002;359(9318):1648-54).
• Schroeder K, Fahey T. Over-the-counter medications for acute cough in children
and adults in ambulatory settings. Cochrane Database Syst Rev. 2004(4):CD001831.
• Nennig ME, Shinefield HR, Edwards KM, et al. Prevalence and incidence of adult
pertussis in an urban population. JAMA 1996;275:1672-4.
• Metlay JP, Fine MJ. Testing strategies in the initial management of patients with
community-acquired pneumonia. Ann Intern Med. 2003;138:109-18.
AECB References
•
Anthonisen NR, Manfreda J, Warren CP et al. Antibiotic therapy in exacerbations
of chronic obstructive pulmonary disease. Ann Intern Med. 1987;106:196-204
•
Snow V, Lascher S, Mottur-Pilson C; ACCP/ACP-ASIM. Evidence base for
management of acute exacerbations of chronic obstructive pulmonary
disease. Ann Intern Med. 2001;134:595-9.
•
Wilson R, Allegra L, Huchon G, et al. Short-term and long-term outcomes of
moxifloxacin compared to standard antibiotic treatment in acute exacerbations
of chronic bronchitis. Chest 2004;125:953-64.
•
Miravitlles M, Torres A. No more equivalence trials for antibiotics in
exacerbations of COPD, please. Chest 2004;125:811-13.
Acute Rhinosinusitis Refs
•
•
•
Lindbaek M, Hjortdahl P, Johnsen UL. Randomized, double blind, placebo
controlled trial of penicillin V and amoxycillin in treatment of acute sinus
infections in adults. BMJ 1996;313(7053):325-9.
Stalman W, van Essen GA, van der Graaf Y, de Melker RA. The end of antibiotic
treatment in adults with acute sinusitis-like complaints in general practice? A
placebo-controlled double-blind randomized doxycycline trial. Br J Gen Pract
1997;47(425):794-9.
van Buchem FL, Knottnerus JA, Schrijnemaekers VJ, Peeters MF. Primary-carebased randomized placebo-controlled trial of antibiotic treatment in acute
maxillary sinusitis. Lancet 1997;349(9053):683-7.
•
Bucher HC, Tschudi P, Young J, et al. Effect of amoxicillin-clavulanate in
clinically diagnosed acute rhinosinusitis: a placebo-controlled, double-blind,
randomized trial in general practice. Arch Intern Med. 2003;163:1793-8.
•
Merenstein D, Whittaker C, Chadwell T, et al. Are antibiotics beneficial for
patients with sinusitis complaints? A randomized double-blind clinical trial.
J Fam Pract. 2005;54:144-51.
Acute Pharyngitis Refs
•
Centor RM, Witherspoon JM, Dalton HP, et al. The diagnosis of strep throat in
adults in the emergency room. Med Decis Making 1981; 1:239-246.
•
Zwart S, Sachs APE, Ruijs GJHM, et al. Penicillin for acute sore throat:
randomised double blind trial of seven days versus three days treatment or
placebo in adults. BMJ 2000; 320:150-154.
•
DiMatteo L, Lowenstein SR, Brimhall B, et al. The relationship between the
clinical features of pharyngitis and the sensitivity of a rapid antigen test: evidence
of spectrum bias. Ann Emerg Med. 2001;38:648-52.
•
Bulloch B, Kabani A, Tenenbein M. Oral dexamethasone for the treatment of pain
in children with acute pharyngitis: a randomized, double-blind, placebocontrolled trial. Ann Emerg Med. 2003;41:601-8.