Upper Respiratory Tract Infections
Upper respiratory tract infections (URTIs) are acute conditions caused mainly by viruses or, more rarely, bacteria, affecting the nose, paranasal sinuses, pharynx, larynx and middle ear.
URTIs are the most frequent reason for outpatient consultations, and in adults they are divided between pharyngitis (25%), rhinosinusitis (25%) and non-specific infections (33%).
In the general population, adults develop an average of 2-3 episodes of URTI per year, while pre-school children have 5-7.
The vast majority of URTIs are viral in origin, caused by over 200 different viruses, while less than 10% are bacterial. However, 20-30% of URTI episodes remain of unknown cause and are presumed to be due to viruses.
RSTIs are transmitted between humans via the respiratory secretions of affected individuals, who can disseminate the infectious agent by sneezing, coughing and the hands, either directly or indirectly via the respiratory tract.
Droplets are probably the most important mode of transmission, but aerosols may play a role in certain situations (see controversy on this subject for SARS-CoV-2). Contrary to widespread belief, there is no scientific evidence that cold weather or exposure to cold directly promotes the onset of URTI. However, it is clear that URTIs are more frequent in winter. Exposure to cold and reduced humidity could weaken the mucous membranes, making viral infections more likely. In addition, the fact that a greater proportion of life is spent indoors in winter could favour transmission.
Although the vast majority of URTIs are viral in origin, 60-80% of patients are prescribed antibiotics in many countries.3 URTIs are very costly because of the very large number of consultations, over-prescription of antibiotics, the resulting consequences (antimicrobial resistance, allergic reactions, C. difficile infections, alteration of the microbiota) and frequent absenteeism from work or school.
Definition and Classification
URTIs can be classified according to the predominant symptom:
- Aspecific URTI: infectious symptoms at several levels, without predominance.
- Acute pharyngitis: predominance of sore throat
- Acute rhino-sinusitis: predominantly nasal symptoms
- Acute otitis media: ear pain predominates
- Influenza: predominance of general symptoms and notion of an epidemic.
Often there is an overlap of symptoms and it is difficult to distinguish between each entity.
Diagnosis and Treatment
SARS-COV-2 and COVID-19
In the vast majority of cases, SARS-CoV-2 is responsible for an URTI, and can be complicated secondarily, usually 7 to 10 days after the appearance of the first symptoms, by a progression of the disease involving the lower respiratory tract.
For each suspected case of covid 19 with symptoms of URTI: wearing of a care mask by the carer and, if possible, the patient; strict observance of hand hygiene, respecting distances, etc.
Aspecific RSVI
Aspecific URTIs are viral in origin, have a benign clinical course and heal spontaneously in 7-10 days on average, but can last up to 14 days.
Diagnosis
An aspecific URTI is clinically manifested by symptoms revealing multiple levels of involvement, none of which is clearly predominant:
- Rhinorrhea, initially clear then often purulent, with nasal obstruction and sneezing, which are the most frequent symptoms, present from the outset and predominant on the 2nd and 3rd days (NB the colour of secretions is of no value in predicting the need for antibiotic treatment).
- Sore throat with moderate swallowing and hoarseness, predominating on the 1st day and disappearing rapidly
- Dry or productive cough that becomes bothersome on days 4 and 5. Typically in cases of COVID-19, respiratory deterioration occurs between 5 and 10 days after the first symptoms
- General symptoms including fever, fatigue and myalgias, which are generally moderate except in cases of influenza, where they are more severe.
On examination, clinical signs are generally absent or minimal, with nasal congestion and pharyngeal hyperhaemia.
The clinical course is spontaneously favourable within 3-10 days.
Diagnosis of aspecific URTI is clinical on the basis of symptoms and clinical examination, and there is no indication for further investigations if the PNF for SARS-CoV-2 is negative, except in cases of suspected complication or suspected influenza in patients at risk of complication.
The diagnostic strategy consists firstly of identifying the minority of patients with a high probability of bacterial URTI, such as streptococcal pharyngitis, pharyngeal abscess, epiglottitis, bacterial rhino-sinusitis or bacterial otitis media.
Clinicians must also identify patients at risk of complications from URTIs, particularly influenza or COVID-19 in the event of an ongoing epidemic. In these patients, it is important to actively search for a possible complication, such as pneumonia, an exacerbation of chronic obstructive pulmonary disease or asthma.
Treatment
The management of any patient with an aspecific, uncomplicated URTI includes general advice on the following points:
- Information on the mildness of the illness, which lasts on average 7-10 days but can last up to 14 days
- Discussion of the patient's expectations and concerns
- Reassurance that an antibiotic is not indicated to improve symptoms and that it can have adverse effects (mild diarrhoea or extremely severe Steven Johnson syndrome) as well as a deleterious long-term effect with the risk of encouraging antimicrobial resistance
- Suggest symptomatic treatment
- Advice to consult again if symptoms worsen or last longer than expected.
Advice on preventing transmission to other people: hand hygiene, wearing a mask, self-isolation, etc.
Acute Pharyngitis
Pharyngitis is the third most common cause of outpatient consultations (4.3%). The vast majority of pharyngitis is viral in origin, while only 5-15% is bacterial, mostly due to Streptococcus pyogenes (synonym: group A β-haemolytic streptococcus [GABHS]).
Diagnosis
The benefit of antibiotic treatment for GABHS pharyngitis relates mainly to the duration of symptoms, which is shortened slightly with antibiotics (1-2 days). The prevention of rheumatic fever (RF) or suppurative complications does not justify antibiotic treatment (very high number of subjects to be treated). Symptomatic treatment without antibiotics with clinical monitoring is therefore even possible in cases of pharyngitis caused by GABHS.
Culture of throat swabs is no longer recommended, and GABHS can now be detected using the rapid detection test (RDT).
Treatment
Antibiotic treatment of GABHS pharyngitis can be discussed with the patient on a case-by-case basis. The recommended strategies are
- Observation, with symptomatic treatment, without antibiotics, is possible even in cases of pharyngitis caused by Group A Streptococcus. Purulent complications are very rare and the "number needed to treat" to prevent a complication is high.
- Antibiotic therapy in adults
1st choice:
- Penicillin V 1 Moi IU every 12 hours PO for 6 days
- Amoxicillin 1 g every 12 hours PO for 6 days.
2nd choice if mild allergy to penicillin:
- Cefuroxime 500 mg every 12 hours PO for 6 days.
3rd choice if absolute contraindication to all beta-lactam antibiotics:
- Clarythromycin 500 mg every 12 hours PO for 6 days.
Other recommendations suggest 10 days' treatment. This duration is not based on solid evidence.
A 5-day course of penicillin antibiotics (but given 4x/d) showed no inferiority in a study comparing it with a 10-day course.
To reduce throat pain and fever, symptomatic treatment in the form of NSAIDs or systemic analgesics is recommended for all patients with acute viral or bacterial pharyngitis.
Topical treatments in the form of a spray or lozenge containing a local anaesthetic or antiseptic are less effective or have not been shown to be effective.
Remember that the differential diagnosis of pharyngitis is wide-ranging and includes primary HIV infection (mononucleosis syndrome) and other sexually transmitted diseases (gonorrhoea).
Acute Rhinosinusitis
Acute rhinosinusitis is an infection of the mucous membranes of the nose and sinuses lasting less than 4 weeks.
In the vast majority of cases, acute rhinosinusitis is viral in origin, most often due to a rhinovirus, influenza virus or parainfluenza virus. SARS-CoV-2 can also occur in this form, and should always be screened for.
Only 0.5-2% of patients have rhinosinusitis of bacterial origin, most often caused by Streptococcus pneumoniae (41%), Haemophilus influenzae (35%) or Moraxella catarrhalis (4%). Bacterial rhinosinusitis is most often the result of superinfection of viral rhinosinusitis, and may also be encouraged by allergy, mechanical nasal obstruction or immunodeficiency.
Diagnosis
Diagnosis of acute rhinosinusitis is based on clinical symptoms and signs, the most characteristic of which are purulent rhinorrhoea, nasal congestion or obstruction, and facial pain, often aggravated by tilting the head forward.
Other symptoms and signs are more uncommon: maxillary dental pain, fever, fatigue, cough, hyposmia or anosmia, headache, ear pain or pressure, halitosis. or anosmia, headache, ear pain or pressure, halitosis.
Viral rhinosinusitis generally resolves in 7-10 days, as does a minority of bacterial rhinosinusitis.
Nasopharyngeal cultures are unreliable and therefore not recommended. Microbiological diagnosis by culture (sinus puncture) is not generally recommended and is only offered if empirical treatment fails.
Clinicians should look for symptoms/severe signs suggestive of rhinosinusitis complicated by meningitis or orbital or periorbital cellulitis, requiring urgent assessment:
- high fever (≥ 39°)
- severe headache
- diplegia
- periorbital oedema or erythema
- reduced visual acuity
- neurological deficit
- mental confusion.
CT-scan imaging of the sinuses is not sufficiently effective and is not recommended as a first-line treatment. It is reserved for cases with purulent complications.
Neither sinus radiography nor MRI is recommended. Mucosal thickening, hydroaerosal levels or complete opacification of the sinus on X-ray are not sufficiently sensitive to differentiate between viral and bacterial rhinosinusitis.
Treatment
Watchful waiting is recommended for all patients with suspected acute rhino-sinusitis of viral or bacterial origin, in the absence of an urgent initial indication for antibiotic therapy. The recommendation for initial management includes symptomatic treatment using the same options as for aspecific URTIs:
- NSAID or analgesic to reduce fever and facial pain
- Nasal vasoconstrictor for viral rhinosinusitis only
- Oral vasoconstrictor alone or with an H1 anti-histamine
- 0.9% NaCl saline solution or intra-nasal seawater.
Intranasal corticosteroid treatment as monotherapy for acute viral rhino-sinusitis or with an antibiotic for acute bacterial rhino-sinusitis with moderate efficacy on symptom resolution (RR=1.11 [IC95% = 1.04-1.18], NPT=15) and minimal adverse effects.
The recommended intranasal corticosteroid treatments are:
- Mometasone (Nasonex ®) 2 x 1-2 nebulisations/narine/d (200-400 μg/day)
- Budesonide (Rhinocort 100 ®) 1-2 x 2 nebulisations/narine/d (200-400 μg/day)
Antibiotic treatment for acute rhinosinusitis is controversial due to studies of limited validity on the definition and diagnostic standard. The most recent meta-analysis confirms moderate efficacy in resolving symptoms (OR1.25, [CI 95 = 1.02 to 1.54], NPT =19 [CI95% = 10-205]) of acute clinical or radiological rhinosinusitis, which is not optimal.
An expert opinion concluded that antibiotic treatment should be recommended to patients with a high probability of bacterial rhinosinusitis according to the criteria defined above and followed for Swiss recommendations:
- Duration of compatible symptoms and signs for ≥ 10 days without improvement
- Signs of severity: high fever (≥ 39.0°C) and purulent nasal discharge or facial pain for at least 3-4 consecutive days
- Worsening of symptoms after initial recovery
- Fever, headache or increased nasal secretion after viral upper respiratory infection
- Duration 5-6 days after initial improvement ("double-sickening")
The antibiotic treatments recommended for acute bacterial rhino-sinusitis are:
1st choice:
- Amoxicillin 1 g 2x or 3x/d PO for 5-7 days
- Special cases: immunosuppressed patients, frontal, ethmoidal, sphenoidal sinusitis and treatment failure after 72 hours of amoxicillin: Amoxicillin-clavulanic acid 2 (sic!) g 2x/d PO for 5-7 days
2nd choice if allergic to penicillin but no contraindications to cephalosporins:
- Cefuroxime 2 x 500 mg/d PO for 5-7 days 2nd choice if allergic to penicillin and contraindicated to all beta-lactams
- Doxycycline 100 mg 2x/d for 5-7 days
The IDSA recommendations (American guidelines) suggest amoxicillin/clavulanic acid in all cases.
Amoxicillin/clavulanic acid offers better coverage for Haemophilus influenzae (around 20-25% of strains are resistant to aminopenicillins), Moraxella catarrhalis (resistant to aminopenicillins) and Staphylococcus aureus, and should be reserved for specific situations. With regard to the frequency of administration, a dose of 1g/12h probably improves adherence to treatment.
If penicillin-resistant pneumococcus is suspected (e.g. a patient from a country with a high prevalence of resistant pneumococcus), a 1g/8h dose of amoxicillin/clavulanic acid should be prescribed.
Acute Otitis Media
Purulent acute otitis media (PAOM) is much more common in children than in adults, occurring as a consequence of an upper respiratory tract infection. While almost 100% of children have had a POMD by the age of three, to our knowledge there are no data on the incidence in adults. The most common germs are Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis.
The most important cause of PAHO is eustachian tube dysfunction.
Diagnosis
Acute otitis media is easily diagnosed by history and otoscopy.
The history may include acute otalgia, hearing loss, fever, purulent discharge from the ear canal if the eardrum has been perforated, and sometimes a history of URTI in the previous few days.
On otoscopy, the eardrum may show erythema, bulging, loss of reflection, transparent fluid level, sometimes a discharge and perforation.
Severe complications of OMAP, which are very rare in adults, include mastoiditis (82%) sometimes associated with facial paralysis, subperiosteal abscess and labyrinthitis, as well as intracranial complications (18%) such as meningitis, intracranial abscess and thrombosis of the sphenoid sinus. Any suspected complication should be referred immediately for emergency hospitalisation.
Blood and microbiological tests are not usually useful.
Treatment
All recommendations for adults have been extrapolated from studies in children.
For the treatment of PAHO in adults, antibiotics have very little effect on the duration of symptoms and recurrence. Complications (e.g. mastoiditis) are rare whether or not antibiotics are prescribed. The benefit of antibiotic treatment in adults is seen in perforated PACO.
Non-antibiotic treatment
- Pain relief (paracetamol or ibuprofen) in all patients.
No benefit from decongestants or antihistamines, which are therefore not recommended.
Antibiotic therapy
Antibiotic treatment may be delayed and initiated within 48-72 hours if symptoms persist or worsen.
Immediate antibiotic treatment is only recommended for perforated PAO (otorrhoea).
1st choice:
- Amoxicillin 1g 3x/day PO for 5 days
- If allergic to penicillin but no contraindications to cephalosporins Cefuroxime 2 x 500 mg/d PO for 5-7 days
Special situations
Antibiotic treatment in the previous 30 days, history of recurrent OMPA.
Risk of colonisation by penicillin-resistant pneumococcus.
No response to amoxicillin after 72 hours of treatment:
- Amoxicillin-clavulanic acid 3 x 1 g /d PO for 5-7 days
2nd choice if allergy to penicillin and contraindications to all beta-lactams:
- Cotrimoxazole: 160mg TMP/800mg SMX 2x/day for 5-7 days
Flu
Influenza A and B viruses cause seasonal influenza epidemics, which generally occur in winter, usually from late December to March. These viruses have a high degree of genetic variability, with frequent mutations leading to the emergence of new viral strains that cause new epidemics every year. Influenza is easily transmitted between humans, leading to a rapid increase in the number of people affected.
The flu surveillance system monitors the epidemic, which is declared as soon as the epidemic threshold of 69 influenza infections per 100,000 population is crossed. Influenza can be complicated by primary viral or secondary bacterial pneumonia, as well as by the decompensation of chronic illnesses responsible for numerous hospitalisations and deaths, the frequency of which increases with age and is 2 to 5 times higher over the age of 65. It should be noted that viral co-infections of SARS-CoV-2 and influenza have been described29, so that infection with SARS-CoV-2 does not rule out influenza infection during the flu season.
Diagnosis
Clinically, influenza is difficult to distinguish from other URTIs. The diagnosis of influenza should be suspected during epidemics and when the clinical picture shows a sudden onset with severe general symptoms.
It is important to identify patients at risk of complications from influenza:
- People aged ≥ 65 years
- Adults of any age with a chronic disease: in particular chronic lung disease (COPD), cardiovascular disease (except isolated hypertension), diabetes or other metabolic disease, renal failure, liver disease, haemoglobinopathy, rheumatological or neurological disease, neoplasia
- Pregnant women of any gestational age and for 2 weeks post-partum
- Residents of care institutions for the elderly or chronically ill
- Severe obesity with BMI ≥ 40 kg/m2
Presence of significant congenital, acquired or iatrogenic immunosuppression, including:
- Severe primary immunodeficiency
- Chemotherapy or radiotherapy < 6 months
- s/p solid organ or bone marrow transplant
- Current or recent immunosuppressive therapy (< 6 months) including (but not limited to) high dose systemic corticosteroid therapy equivalent to > 40 mg prenisone daily for >= 1 week, up to 3 months after discontinuation of therapy
- HIV infection with CD4 < 200/mm3 or < 15% of total lymphocytes.
The most common complications of influenza are pneumonia, bronchitis, bacterial (mainly S. aureus) or fungal (Aspergillus spp.) superinfections, worsening of underlying chronic disease (asthma, chronic obstructive pulmonary disease (COPD), diabetes, heart failure), as well as rare cardiac (myo-pericarditis) and neurological complications. These complications must be actively sought during consultations.
The diagnosis of certainty is based on the detection of influenza A/B by PCR on a nasopharyngeal swab (FNP) (at the HUG we use a mini PCR panel which also detects RSV).
- This test is only carried out during the influenza season (November-December to March-April), except in exceptional circumstances (e.g. return from a tropical country)
- Time taken to obtain results: 20 minutes if done on the emergency department POCT (LIAT), © 24 hours after receipt if the FNP is sent to the laboratory.
Who should undergo an FNP?
In outpatients, an FNP to test for the influenza virus is indicated during an epidemic in all patients in whom the result will alter the therapeutic or public health medical intervention, i.e.:
- immunosuppressed patients and patients at increased risk of complications
- and with symptoms of URTI, pneumonia, or a febrile state associated with cough or odynodysphagia.
A test may be discussed for outpatients who are not at risk of complications and who do not require hospitalisation, presenting with URTI, pneumonia or non-specific symptoms of febrile state associated with cough or odynodysphagia if the test result:
- Can influence the prescription of antiviral drugs (if symptoms last ≤ 48 hours and there are no risk factors for complications)
- Enables antibiotic consumption to be reduced
- If the patient is a close contact of an immunosuppressed patient who could benefit from chemoprophylaxis
All patients requiring hospitalisation during a period of influenza and presenting with symptoms of lower respiratory tract infection (pneumonia), with or without fever, should have an FNP to test for the influenza virus. Patients requiring hospitalisation and presenting with upper respiratory tract symptoms should also have a PNF, particularly for reasons of isolation/infection control.
It should be noted that influenza can present without fever in certain sub-groups of patients, including those aged over 65 and immunosuppressed patients; the absence of fever does not therefore rule out an influenza infection if the clinical picture is compatible.
Treatment
Symptomatic treatment is recommended for all patients with suspected influenza, including the same options as for aspecific URTI:
- NSAIDs or analgesics to reduce fever, myalgia and pain
- Nasal vasoconstrictor for viral rhinosinusitis only
- Oral vasoconstrictor alone or with an H1 anti-histamine
Antiviral treatment with neuraminidase inhibitors is not routinely indicated due to their limited efficacy, high cost, risk of increasing resistance and the need to initiate treatment within 48 hours of the onset of symptoms. These anti-virals were modestly effective in reducing the duration of symptoms by around 0.6 days ([CI95% = 8.4 to 25.1 hours, P © 0.0001]) but had no effect on hospital admissions (risk difference (RD) 0.15% (95% CI -0.78 to 0.91)).
The earliest possible antiviral treatment is recommended, ideally within 48 hours, but also beyond that in the event of rapid worsening of symptoms in the following indications:
- Patients with confirmed or suspected severe influenza requiring hospitalisation
- Patients at risk of complications with confirmed or suspected influenza.
In practice, it is advisable to wait for the result of the diagnostic NPF test if the sample is treated in the emergency department (use of the Liat POCT, result in approximately 20 minutes). In order not to delay the initiation of treatment, if the FNP is sent to the virology laboratory (or if the Liat POCT is unavailable), it is suggested that anti-viral treatment be started without waiting for the result of the diagnostic test, and that the need for it be reassessed on the basis of the results.
Anti-viral treatment may be considered:
- in patients at risk of complications whose symptoms begin >= 48h
- patients not at risk of complications but whose symptoms last < 48 hours
- who are symptomatic, and who are close contacts of an immunosuppressed patient or a patient at risk of complications
- in patients at no risk of complications whose symptoms have been evolving for less than 48 hours.
There is no indication for antiviral treatment in patients with no risk factors for complications, with uncomplicated influenza and symptoms that have been evolving for more than 48 hours.
For outpatient oral treatment, which are oseltamivir and baloxavir (neuraminidase inhibitor) Oseltavimir (Tamiflu®), therapeutic dose, PO, to be adapted to renal function:
- 75 mg 2x/day for 5 days if Clearance >=30 mL/min
- 75 mg 1x/day for 5 days if Clearance between 15 and 30 mL/min
- 75 mg as a single dose if Clearance < 15 mL/min
- 30 mg after each dialysis session for haemodialysis patients
- 30 mg 1x/week for patients on peritoneal dialysis
The major adverse effects are nausea and vomiting.
Other antiviral treatments are available and may be discussed with the infectious diseases consultant in specific cases where oseltamivir cannot be prescribed (e.g. baloxavir).
The initiation of any treatment should be reassessed once the results of the FNP have been received, and oseltamivir treatment should be stopped if influenza has been ruled out.
Prevention
We can recommend 6 measures to prevent URTIs:
- Wear a mask if a distance of 1.5 m cannot be maintained between 2 people.
- Washing or disinfecting hands to reduce the transmission of URTI viruses.
- Seasonal influenza vaccination: the simplest, most effective and most economical way of protecting yourself and those around you.
- Pneumococcal vaccine: Prevnar 13®.
- Smoking cessation for smokers who have a 1.5 times higher risk of URTI, which could be reduced by stopping smoking.
- Post-exposure prophylaxis with oseltamivir against seasonal influenza in patients with significant immunosuppression.
In addition, to limit transmission of SARS-CoV-2 during a COVID-19 epidemic, a broad and early strategy of testing the population for any respiratory symptoms and/or fever, whatever their severity, repercussions or co-morbidities, makes it possible to rapidly identify infected patients, treat them, isolate them and monitor their contacts to limit the spread of the virus.
Patients with significant immunosuppression AND exposed to influenza (sharing the same room as a person with confirmed influenza, or having had prolonged, repeated, unprotected contact at less than one metre with a patient confirmed to be infected with influenza) may benefit from a 10-day course of oseltamivir prophylaxis, adapted to renal function.
Post-exposure prophylaxis may also be considered for unvaccinated people living with an immunosuppressed person.
This treatment should be started within 48 hours of exposure. After this period, it is advisable to monitor the patient closely, and to introduce curative treatment as soon as the first symptoms compatible with influenza develop.
Oseltavimir (Tamiflu®) PO, prophylactic dose, to be adapted to renal function:
- 75 mg 1x/day for 10 days if renal clearance >=30 mL/min
- 75 mg 1x/day for 10 days if Clearance between 15 and 30 mL/min
- No data available if Clearance < 15 mL/min
- 30 mg after every 2 dialysis sessions for haemodialysis patients
- 30 mg 1x/week for peritoneal dialysis patients.
In the event of recent exposure to oseltamivir, contact the infectious diseases department to discuss alternative prophylaxis. The history of vaccination should not be taken into account when deciding whether or not to institute treatment or prophylaxis.
Patients receiving prophylactic doses of oseltamivir should be monitored regularly so that treatment can be adapted if symptoms compatible with influenza develop.
Pre-exposure prophylaxis is never recommended.