Download Upper Respiratory Tract Infections

GUIDELINES
Guidelines
l
Upper Respiratory Tract Infections
Nadine Butler, MPharm, PhD
School of Pharmacy, University of the Western Cape
Introduction
The most important concern in the management of upper
respiratory tract infections (URTIs) is antibiotic resistance.
Worldwide evidence suggests that inappropriate antibiotic use
for non-severe URTIs, most of which are viral, adds to the
overall burden of antibiotic resistance, a phenomenon which
is becoming more prevalent.1 This has been the rationale for
the compilation of treatment guidelines for the management of
URTIs in South Africa. The initial guideline was drawn up following a meeting of the Infectious Diseases Society of Southern Africa in 2003; at this meeting randomised controlled trials,
existing URTI treatment guidelines and local antibiotic resistance patterns were examined, culminating in the publication
of a consensus document in 2004.2 The same group, including
overseas experts, decided in 2008 to update the guideline
(published in 2009), which incorporates the following newly
available information:
•• The introduction of new antibiotics (e.g. gemifloxacin) or
new formulations of existing antibiotics (e.g. amoxicillin/
clavulanic acid)
•• Trends in antibiotic pharmacokinetic/pharmacodynamic parameters which impact on previous guideline
recommendations
•• The potential impact of the 7-valent pneumococcal conjugate vaccine on otitis media
•• Acute otitis media with otorrhoea in patients with tympanostomy tubes3,4
Low-grade fever, malaise,
myalgia, anorexia
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The guideline specifies first-line antibiotic recommendations for
the following conditions:
•• Acute pharyngotonsilitis
•• Acute otitis media
•• Acute bacterial sinusitis
Alternative choices of antibiotics are also recommended under
one or more of the following conditions:
•• Allergy or intolerance to first-line agents
•• Recent prior use of first-line agents
•• High-risk cases likely or known to be infected with highly resistant organisms (usually ß-lactam and macrolide resistance)
•• Failed initial therapy4
Organisms responsible for URTIS
Although the term URTI implies a problem located in the upper
airways, it is inevitable that both the upper and lower airways
would become involved to a variable degree. The majority of URTIs are viral in origin (including the Epstein Barr virus), resulting
in damage to the ciliary apparatus and mucosal epithelium. Since
the nerve endings are exposed, the airway becomes sensitised
to the irritational effect of inhaled substances and to secretions.
The clinical symptoms of these viral infections usually resolve
within two weeks, but the airway irritability may persist for six to
eight weeks.5 Given the viral nature of the majority of the URTIs,
it is important that the natural history of the common cold be well
recognised, so that the appropriate management can be applied
to any deviations from the normal progression of the disease.
Figure 1: Natural history of the common cold4
Nasal stuffiness
and throat irritation
Sneezing and watery nasal
discharge
Cough in 60–80% (does not imply
bacterial disease)
Mucopurulent secretions
(1–3 d later)
Persists up to 10 days in 35%
Persists up to 10 days in 31%
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GUIDELINES l
Of clinical importance in the management of the common cold
is the recognition that clear nasal secretions frequently become
purulent; this is however not indicative of secondary bacterial
infection, thus antibiotic therapy is not automatically indicated.
Coughing is a normal accompaniment.
Irrespective of age group, URTIs involving bacterial infection are
commonly otitis media and sinusitis caused by Streptococcus
pneumoniae and pharyngitis caused by Streptococcus pyogenes. Systematic reviews have suggested that using antibiotic therapy for the treatment of pharyngitis and otitis media in
developed countries is only of extremely limited benefit. Good
data from less developed countries, where there is a greater
prevalence of rheumatic fever and suppurative complications,
for example mastoiditis, is not available; therefore the doubtful
antibiotic benefit cannot be extrapolated globally.6,7 In the underdeveloped rural parts of South Africa, there is evidence of a high
prevalence of rheumatic fever, despite poor notification rates.
Adherence to antibiotic therapy
Although patient non-adherence to prescribed regimens is an
important issue throughout clinical practice, the emergence of
antibiotic-resistant bacteria implies that patient non-adherence,
specifically to antibiotic therapy, is particularly worrying. When a
patient with an URTI either delay starting their antibiotic therapy or
miss one or more doses, plasma levels of the antibiotic may fall
below the minimum inhibitory concentration (MIC), but remain
high enough for the development of antibiotic resistance. Since
experience has shown that no definitively effective measures to
combat non-adherence, via changing patient behaviours, have
been identified, the focus has shifted instead to simplifying antibiotic dosage regimens and assessing the comparative efficacy
of short-course therapy.8 The guideline includes alternative options of short-course (3–5 days) antibiotic therapy.4
Acute pharyngotonsilitis (sore throat)
Definition: Acute pharyngotonsilitis (sore throat) is an inflammatory condition of the wall of the pharynx, sometimes divided
into tonsillitis and pharyngitis, most commonly caused by respiratory viruses. 5–30% of cases would be bacterial; caused by
S. pyogenes, a group A ß-haemolytic streptococcus (GABHS).
Non-infectious causes include allergy or exposure to irritating
substances. Most cases of GABHS are self-limiting; antibiotic
therapy is however indicated to prevent post-streptococcal sequelae of acute rheumatic fever or glomerulonephritis, common
in poor rural and urban areas of South Africa.
Evidence suggests that intramuscular (IM) penicillin prevents
rheumatic fever; although this route of administration is not
popular, it is preferred, particularly there is suspicion that either
the patient would not adhere to the oral regimen or would not
present for follow-up, if needed. The discomfort associated with
the IM injection could be minimised by giving the medication at
room temperature. As shown in Figure 2, penicillin is the drug
of choice (given orally or IM). Amoxicillin could also be used,
having the advantage of no food restrictions; the disadvantage
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is that amoxicillin, when used when the infection is due to the
Epstein Barr virus, could cause a rash, which could be incorrectly diagnosed as a penicillin allergy.
Recommended short-course therapy for bacterial sore throat,
intended to maximise patient adherence and so minimise antibiotic
resistance, include the following (including the new macrolides
and second-generation cephalosporins, which have been found to
be equivalent in efficacy to penicillin given three times a day for 10
days): Note: regimens are for five days unless otherwise specified.4
Children:
•• Amoxicillin-clavulanate, 40 mg/kg/day in three divided doses
•• Azithromycin, 10–20 mg/kg once daily for three days
•• Clarithromycin, 7.5 mg/kg twice daily
•• Cefpodoxime, 4 mg/kg twice daily
•• Cefproxil, 7.5 mg/kg twice daily
•• Cefuroxime, 10 mg/kg twice daily
Adults:
•• Amoxicillin-clavulanate, 375 mg three times daily
•• Azithromycin, 500 mg once daily for three days
•• Clarithromycin (modified release), 500 mg once daily
•• Cefpodoxime, 100 mg twice daily
•• Cefproxil, 500 mg twice daily
•• Cefuroxime, 250 mg twice daily
•• Telithromycin, 800 mg once daily
Acute otitis media
Acute otitis media (AOM) is one of the most common childhood
diseases; by the time a child has reached three years of age, it is
estimated that 75% would have had more than one episode. Higher
prevalence rates are recorded in children less than two years of age,
attending a day-care facility and/or exposed to passive smoking.9
Typical causative bacteria for AOM are S. pneumoniae, nontypable Haemophilus influenzae and Moxarella catarrhalis.
Infections caused by the last two bacteria typically show a high
rate of spontaneous resolution (around 60–70%) but the S.
pneumoniae infections are the least likely to resolve spontaneously, thus represent the most important target for antibiotic
therapy. A particular concern in the antibiotic treatment of AOM
is the poor permeability of the middle ear fluid to antibiotics and
the ensuing higher risk of development of antibiotic resistance.
The recommended treatment options given for AOM in Figure 3
mostly refer to the treatment of the condition in children. In adults,
the treatment recommendations for AOM are exactly the same
as for acute bacterial sinusitis (see Figure 4). Particularly for older
infants, a recommendation has been made that antibiotic therapy
for AOM should be postponed for 48 hours in favour of analgesic
and decongestant treatment. The rationale for this lies in both the
fact that the infection could probably be of viral origin, and in the
high rates of spontaneous resolution of AOM.10 The guideline,
while acknowledging that this approach is reasonable, still recommends that in South Africa, given the risks of a serious infection
with S. pneumoniae and the reality that many patients would
not return for follow-up after the 48hour period, that all cases of
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GUIDELINES
Guidelines
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Figure 2: Recommended treatment for sore throat4
SORE THROAT
Clinical diagnosis of streptococcal pharyngotonsillitis
Symptom cluster = Points in favour of empiric antibiotic therapy
• Acute onset
• Temperature > 38o
• Tender anterior cervical nodes
• Tonsilar erythema or exudates
• Age 3–15 years
• Previous rheumatic fever or rheumatic heart disease
BACTERIAL
INDICATIONS FOR REFERRAL
Local complications:
• Peritonsillar sepsis and/or asymmetric peritonsilar swelling
• Recurrent infections (≥ 4 x /year)
• No response to initial Tx
Systemic complications:
• Acute rheumatic fever
• Severe systemic illness
Symptom cluster = Points against empiric antibiotic
therapy
• Rhinorrhoea
• Cough
• Diarrhoea
• Conjunctivitis
• Age > 45 years
VIRAL
Treat symptomatically
No empiric antibiotics indicated (unless +ve throat
swab)
REFER IF
COMPLICATIONS
OCCUR
TREATMENT OF CHOICE
(if no reason to refer)
DRUG OF CHOICE: Penicillin
Children:
Oral Penicillin VK
•≤ 27 kg: 250mg bd, x10d (30 min before meals)
•> 27 kg: 500mg bd, x10d (30 min before meals)
OR Intramuscular Benzathine penicillin;
•3–5 yrs: 600 000 U
•> 5 yrs: 1,2 MU
Adults and adolescents:
•
Oral: 500mg Pen VK bd, 10d OR
•
IM: 1,2 MU benzathine penicillin OR
•
IM: 900 000 U benzathine penicillin PLUS
300 00 U procaine penicillin
ALTERNATIVE TREATMENTS
PATIENTS with SEVERE BETA LACTAM ALLERGY
Children:
•Erythromycin estolate, 40 mg/kg bd, x 10d
•Azithromycin, 10–20 mg/kg once daily, x 3d
•Clarithromycin, 7.5–15 mg/kg bd, x 5d
Adults:
•Erythromycin estolate, 500 mg bd, x 10d
•Azithromycin, 500 mg once daily, x 3d
•Clarithromycin (modified release), 500 mg once daily, x 5d
•Telithromycin, 800 mg once daily, x 5d
SPECIAL INVESTIGATIONS
Throat swabs should be reserved
for patients with recurrent sore throats
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Figure 3: Recommended treatment for acute otitis media4
ACUTE OTITIS MEDIA (AOM)
Clinical diagnosis of AOM
•
•
•
Visualisation of tympanic membrane essential for diagnosis
Bulging, red or yellow tympanic membrane
Ancillary features include:
– Otalgia
– Temperature > 38o
•
NOTE: Effusion alone is not an indication for antibiotic
therapy
INDICATIONS FOR REFERRAL
•
•
•
•
•
If tympanic membrane not visualised
Non-responsive AOM (after 3d Tx)
Suspected intracranial extension
Lower motor neuron VIIth nerve palsy
Suspected mastoiditis
TREATMENT OF CHOICE
DRUG OF CHOICE: Oral amoxycillin
Children:
• 90 mg/kg/day in 2–3 divided doses, x 5–7d
• If < 2 years, recurrent or chronic AOM or complicated cases,
x 7–10d
Adults:
• 1000 mg tds x 5d
ALTERNATIVE TREATMENTS
ALTERNATIVE ANTIBIOTIC CHOICES
Children:
• Amoxicillin-clavulanate, plus additional amoxicillin (to a total
dose of amoxicillin 90 mg/kg/day in 2–3 divided doses,
x 5–7d)
• Cefpodoxime proxetil, 8–16 mg/kg bd, x 5–7d
• Cefproxil, 15–30 mg/kg, bd, x 5–7d
• Cefuroxime axetil, 15–30 mg/kg bd, x 5–7d
PATIENTS with SEVERE BETA LACTAM ALLERGY
Children:
• Erythromycin estolate, 40 mg/kg bd, x 5–7d
• Azithromycin, 10 mg/kg once daily, x 3d
• Clarithromycin, 7.5–15 mg/kg bd, x 5–7d
• Cefpodoxime proxetil, Cefproxil, Cefuroxime axetil. As above
FAILED THERAPY
Children:
• Amoxicillin-clavulanate, plus additional amoxicillin (to a total
dose of amoxi cillin 90 mg/kg/day in 2–3 divided doses,
x 5–7d) for failed therapy with amoxicillin alone
• Ceftriazone, IV or IM, 50–75 mg/kg once daily x 3d. (Also
recommended for known high-level antibiotic resistance)
SPECIAL INVESTIGATIONS
None recommended
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definitively diagnosed AOM be initiated on antibiotic treatment immediately. Of importance here is the diagnosis; the AOM must be
differentiated from otitis media with effusion (glue ear). Antibiotic
therapy is considered essential in the following patients:
•• Recurrent AOM
•• Immunocompromised
•• Neonates
•• Structural ENT or immunological abnormalities
•• Fever (temperature > 38o) or pain > 48 hours
•• Day-care attendees or their siblings.
Paracetamol (10–15 mg/kg 4–6 hourly) or ibuprofen (10 mg/kg 8
hourly) are recommended for pain. The use of decongestants in
the treatment of AOM is controversial. If used, topical administration for not more than three days is preferred to the oral route.
An addition to the current guideline is information pertaining to the
treatment of acute otitis media in patients with tympanostomy tubes
(AOMT). This has not previously been considered as a separate
clinical entity in the treatment of URTIs. It has been found that,
unlike AOM, the otorrhoea fluid is likely to contain other bacteria –
Psuedomonas aeruginosa or S. aureus – in addition to the usual
pathogens. The recommended treatment is ciprofloxacin 0.3%/
dexamethasone 0.1% otic suspension, four drops twice daily for
seven days. In addition to the installation of the eardrops, it is
recommended that the external ear canal/s be suctioned, using a
disposable nasal aspirator, prior to use of the drops. Tragal (on the
cartilage projection anterior to the external opening of the ear) pressure should be applied after the drops are instilled in order to push
the drops through the tympanostomy tubes into the middle ear.
Acute bacterial sinusitis
Acute bacterial sinusitis (ABS) is commonly preceded by a viral
URTI. Inflammation of the nose and paranasal sinuses, caused
by allergy, trauma or dental infection, typically predispose patients
to ABS. ABS is similar to AOM in terms of the typical causative
bacteria and in terms of S. pneumoniae being most problematic,
thus occasioning antibiotic therapy. Other streptococcal species,
anaerobic bacteria and S. aureus occur in a small percentage of
cases. Atypical pathogens, for example Chlamydia pneumonia or
even fungi, have been known to be the causative organisms.r
References
1. Jacobs MR. World trends in antimicrobial resistance among common respiratory tract pathogens in children. Pediatr Infect Dis J 2003; 22: S109 – s119.
2. Working Group of the Infectious Diseases Society of Southern Africa. Guideline for
the management of upper respiratory tract infections. SAMJ 2004: 94(6):475–483.
3. Editorial. Revised guideline for the management of upper respiratory tract
infections. South Afr J Epidemiol Infect. 2008;23(4):3.
4. Working Group of the Infectious Diseases Society of Southern Africa.
Updated guideline for the management of upper respiratory tract infections in
South Africa:2008. SA Fam Pract. 2009: 51(2):105–114.
5. Bösenberg AT. The child with a runny nose! Upper respiratory tract infection
in children: the impact on anesthesia. SAJAA 2007;13(2):33–35.
6. Del Mar C. Managing sore throat: a literature review. Med J Aust 1992;156:
572–575.
7. Del Mar CB, Glasziou PP, Spinks AB. Antibiotics for sore throat (Cochrane
Review). In: The Cochrane Library, Issue 4, 2003. Chichester, UK: John
Wiley & Sons, 2003.
8. Jones S. Respiratory tract infections and high-dose short-course antibiotic
therapy. SA Pharm J.2009; Apr: 26–28.
9. Hoppe HL, Johnson CE. Otitis media: focus on antimicrobial resistance and
new treatment options. Am J Health Syst Pharm 1998;55(18):1881–1897.
10. Del Mar C, Glasziou P, Hayem M. Are antibiotics indicated as initial treatment for
children with acute otitis media? A meta-analysis. BMJ 1997;314: 1526–1529.
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Guidelines
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Figure 4: Recommended treatment for acute bacterial sinusitis4
ACUTE BACTERIAL SINUSITUS (ABS)
Clinical diagnosis of ABS
ALTERNATIVE TREATMENTS
Consider in adults or children with an URTI that is NOT improving after 10d OR worsens after 5–7d and is accompanied by
some or all of the following symptoms:
• Fever
• Facial tenderness, particularly unilateral or focused in the
region of a sinus group
– Peri-orbital
– Maxillary
– Frontal
– Ethmoidal
• Dental tenderness
• Nasal discharge, nasal congestion, anosmia (loss of sense
of smell), cough, ear fullness and pressure
ALTERNATIVE ANTIBIOTIC CHOICES
NOTE: Frontal sinusitis does not occur in toddlers < 4 years
because of delayed development of the frontal sinuses
PATIENTS with SEVERE BETA LACTAM ALLERGY
INDICATIONS FOR REFERRAL
•
•
•
•
•
Non-responsive ABS (after 72 hr Tx)
Peri-orbital swelling
Evidence of CNS extension (meningism, focal neurological
signs, altered level of conciousness)
Suspected systemic illness
Chronic sinusitis – symptomatic for > 30d
TREATMENT OF CHOICE
DRUG OF CHOICE: Oral amoxicillin
Children:
• 90 mg/kg/day in 2–3 divided doses, x 10d
Adults:
• 1000 mg tds, x 10d
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Children:
• Amoxicillin-clavulanate, plus additional amoxicillin (to a total
dose of amoxicillin 90 mg/kg/day) in 2–3 divided doses, x 10d
• Cefpodoxime proxetil, 8–16 mg/kg bd, x 10d
• Cefuroxime axetil, 15–30 mg/kg bd, x 10d
Adults:
• Amoxicillin-clavulanate, 1 g bd plus amoxicillin 500 mg OR
2 g sustained release (SR) bd x10d
• Cefpodoxime proxetil, 200–400 mg bd, x 10d
• Cefuoxime axetil, 500 mg – 1 g bd, x 10d
Children:
• Erythromycin estolate, 40 mg/kg bd, x 10d
• Azithromycin, 10 mg/kg once daily, x 3d
• Clarithromycin, 7.5–15 mg/kg bd, x 10d
• Cefpodoxime proxetil, Cefuroxime axetil. As above
Adults:
• Erythromycin, 500 mg qid, x 10d
• Azithromycin, 500 mg once daily, x 3d
• Clarithromycin (modified release), 1g once daily, x10d
• Telithromycin, 800 mg once daily, x 5–10d
• Gemifloxacin, 320 mg daily, x 5–10d
• Levofloxacin, 500 mg bd or 750 mg once daily, x 5–10d
• Moxifloxicin, 400 mg once daily, x 5-10d
• Clindamycin, 450 mg tds, x10d
• Cefpodoxime proxetil, Cefuroxime axetil. As above
FAILED INITIAL THERAPY
Children:
• Amoxicillin-clavulanate, plus additional amoxicillin (to a total
dose of amoxycillin 90 mg/kg/day) in 2–3 divided doses, x 10d
– for failed therapy with amoxicillin alone
• Ceftriazone, IV or IM, 50–75 mg/kg once daily, x 3–5 days. Also
recommended for known high-level antibiotic resistance
Adults:
• Amoxicillin-clavulanate, 1g plus additional amoxicillin 500 mg,
bd OR 2 g SR, x 10d – for failed therapy with amoxicillin alone
• Gemifloxacin, levofloxacin, moxifloxacin, telithromycin As above
• Cefriazone, IV or IM, 1–2 g once daily for 3–5 d
SPECIAL INVESTIGATIONS
•
•
•
•
X-rays are of limited value
CT scans should be reserved for cases in which surgery is
considered
Nasal swabs for microbiological investigation are of no value
Specimens for culture and microscopy should be collected from
sinus puncture
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