Acute diseases of the upper respiratory tract- 2010 English version of ‘doenças agudas de vias

aéreas superiores

Dario Palhares

Pediatrician of the University Hospital of Brasília

Email: dariompm@unb.br

Objectives of this class

1) To know the most important virus that infect the upper respiratory tract

2) To clinically differentiate the viral diseases from the bacterial ones (accepting that there may be overlapping of signs and symptoms)

3) To rationally choose the antibiotics, based on the prevalent bacteria and on the profile of sensitivity

Roadmap of the class

Brief review on anatomy and physiology of the upper respiratory tract

The virus of flu/cold Clinical manifestations of flu/cold Acute medium otitis Microbes of bacterial otitis Acute sinusitis

Specifities of the paranasal sinus in childhood

At birth: maxillary sinus

some ethmoidal cells

Sphenoid sinus: after 3 years

Frontal sinus: after 6 years.

The mucosa

The mucosa produces mucus

Ciliated cells, continous cilliar movement

Rhynopharynx: colonized by aerophilic bacteria

Physiologically, bacteria from pharynx and also from the gut (physiological episodes of reflux) reach the Eustachii tuba and the paranasal sinus

Mechanisms for maintenance of sterility on Eustachii tuba and paranasal sinus:

Mucocilliary clearance (load the secretions into the gut)

Sneezes Blowing the nose (small children lack this mechanism)

Conclusion: the respiratory system is very vulnerable

From the Tao “Everything is born with its own germen of the self destruction”

Acute viral rhynopharingits: vulgarly, flu. Secretory otitis

Acute medium otitis

Asthmatic crisis Facial palsy

FLU Mastoiditis

Alleric rhinitis Pneumonia

Acute bacterial sinusitis Thrombosis of cavernous sinus

Periorbital cellulitis Cerebral abscess

Discompensationof chronic diseases

Febrile convulsions

Acute viral rhynopharingits Flu: caused by the influenza virus

Common cold: ohter virus:

Rhinovirus ( > 100 sorotypes)CoronavirusParainfluenzaRespiratory syncytial virus (also causes bronchiolitis)

Adenovirus

All the aerial transmitted virus (exantematic diseases, rotavirus, etc).

Flu X common cold: clinically indistinguishable.

Epidemiologically, the influenza virus caused pandemics with a great mortality

Influenza Virus

Etymology: influence, from Italian influenza. Word created in the epidemy of 1733, in allusion to divine punishments.

RNA – vírus

Family Orthomyxoviridae

Classified according to antigens from the surface proteins and matrix proteins:

Influenza A, B, C.

Influenza

Influenza B and C: antigenically stableInfluenza A: variations in the surface proteins (Hemagglutinin

and Neuraminidase) with diverse recombinations.

Birds in general are naturally reservoirs of these virus

They were described with 16 antigenic groups of hemagglutinins and 9 of neuraminidases

Influenza

In human populations, only three major groups of Hemagglutinin (H1, H2 and H3) and two of neuraminidases (N1 and N2) have been found.

Natural cycle of influenza in human populations: epidemics at each 3 years, pandemics at each 40 years in average

Influenza

Historic Pandemics:

1918: virus type H1N1. Mortality of 2,5%. Inside the chaos of the First World War.

1958: virus type H2N2. Mortality of 0,03%

1968: virus type H3N2. Mortality of 0,03%

Influenza

“Asiatic chicken flu” of 2008:

373 confirmed cases, 236 deaths.

Virus type H5N1.

Which means, zoonosis with a reduced ability of human transmission.

Swine flu of 2009: virus H1N1

Influenza

Seasonal epidemics: USA estimative: 30 mil annual deaths, mainly in the winter and in sick population (elderly, chronic diseases).

Babies and children present with too many medical consults and internments, but with a low mortality.

Influenza

Vaccin: does not protect against flu

It would protect against grave forms of flu and against post-flu pneumonia

Most recent studies have shown that the vaccination of the elderly does not alter the mortality rate of respiratory diseases: it is possible that the vaccine will be removed from the official vaccine calendar (but there are high economic interests involved)

Anti-influenza drugs

Two classes: inhibitors of M2 protein (surface

protein, less variable than hemagglutinins and neuraminidases): rimantadina and amantadina.

They were removed from the market because they quickly (three days in average) selected resistant virus, which preserved their infectivity and virulence

Amantadina: still present for the treatment of Parkinson´s disease

Influenza

Antivirals: inhibitors of the neuraminidase: oseltamivir and zanamavir.

The pandemic of 2009 showed that they don´t alter the natural history of the infection, even in the grave forms

Influenza

Serious denunciation:

“ The data over the effectivity of oseltamivir (...) come mainly from a single study (...) one metanalysis of 10 clinical essays that presented a mix of published and unpublished data (...) inaccessible to the free scrutiny”

Jefferson and cols, BMJ Brasil, fev/2010.

Adenovirus

They cause rhynopharingitis and also:

Conjunctivitis Parotiditis Gastrenteritis Hemorragic cystitis (uncommon) Viral meningitis

Clinical features

Fever: of any value (higher temperatures are not related to severity)

Cough Rhinorrhea, nasal obstruction Lachrymation Otalgia Pharingitis: it is common to present edema of tonsils with mild

hyperemia (clinical subjectivity) Cephalea: mild, related to fever, quick respond to the analgesic

Inappetence Crisis of laryngospasm

Fever

Hours of peak: between 4 pm and 6 pm

It is common to appear at predawn

It can enhance intensity and frequence in the first three days, stabilizes until the 5th day and then starts to lower down.

Rhinorrhea

Initially, aqueous Becomes mucoid Ends as mucopurulent It is common to be more purulent at

awakening than the rest of the day

Anterior rhinoscopy: hyperemic mucosa. Paleness, violet musoca: allergic rhinitis or use of vasoconstrictors

Otalgia

Hiperemia of tympanum and/or auditory canal SUGGESTS VIRAL INFECTION

Sudden beginning, when exposure to cold: SUGGESTS VIRAL INFECTION

Inappetence

Due to the greater ingestion of the nasal secretion (mucociliar clearance)

It is not a factor for prognosis, however, the recovery of the appetite indicates clinical ammelioration

Crisis of laryngospasm

Often occurs during predawn Rapid alleviation with inhalation of water

vapour

Attention: high fever of sudden beggining + laryngospasm = malignant laringitis by Heamophilus (uncommon after the massive vaccination)

Seasonality

Varies according the place Related to unfavourable climatic periods.Ex: temperate regions: winter in Alaska: beginning of spring (the winter

imposes complete isolation) in Brasília: march/april (autumn): days too

hot and cold nights in Salvador (Bahia): september/october:

rainy season

Exposition to cold weather

Alone, it does not cause flu (obvious)

However, can start a crisis of allergic rhinitis (whose clinical features are very similar)

It may weaken the respiratory defenses (especially sudden changes of temperature) hence enhancing the chance of a sinusitis, otitis, pneumonia

Annual attacks

In general, each child has 3 to 12 episodes per year

The entrance in nurseries and schools enhances the incidence

Laboratory

Hemogram: first 2 days: inespecific response to aggression: leukicitosis (up to15.000 leukocytes/mL) with neutrophilia

After 2 days: normal leukometry or slight leukocitosis (up to 12.000 leukocytes/mL) with lymphocytosis or neutrophils and lymphocites in equal proportion

Radiography of thorax

May present diffuse interstitial congestion (needs to correlate to the clinical manifestations)

Prophylaxis

Delay the entrance in nurseries

The questionable vaccine against the influenza is indicated only to elders and to special groups

Treatment

1) Measure axillary temperature and give analgesics: dipirone, ibuprofen, paracethamol. AAS is formally contraindicated due to the risk of Reye´s syndrome.

2) Frequent nasal cleaning with saline solution 3) Frequent oral hydration 4) Keep the normal and healthy diet and avoid junk

food 5) Protect against cold weather 6) Keep attention to the signs of bacterial

complication

The antigripal formulas

READ the bula

Generally: analgesic + anti-histaminic + systemic nasal vasoconstrictor + caffeine

Which means: fight the fever, the allergic rhinitis and the sonolence induced by the anti-histaminic

Avoid in children, especially in babies. Pharmacon = poison!

Peculiar situations

1) Recent fever, good general presentation (prodromic phase):

Since this situation can refer to any infectious disease, prescribe analgesics and give a WRITTEN ORDER to re-evaluate the child in 2-3 days.

Peculiar situations

2) Referred fever, but not measured, good clinical presentation:

Teach to measure axillary temperature, re-evaluation in 2 days if fever is really happening

Peculiar situations

3) Fever + aqueous nasal secretion IN NEONATES (less than 30 days of life), even if the general aspect is good:

INTERNMENT IS INDICATED

If it is the case, give a WRITTEN ORDER to re-evaluate the baby in 48 hours.

In general, the baby will spend just an overnight period in the hospital, but be careful with fevers in this period of life

Signs of bacterial complication

Clinical worsening (enhancement of fever, of prostration, of coughing, of otalgia, of cephalea): a degree of subjectivity of the examinator will always be present

Appearance of tachypneia during resting Recrudescence of fever Delay in ammelioration (often with good

general aspect, but with a ‘cold that doesn´t go away’)

Acute otitis media

Definition: acute (less than 4 weeks) infection of the medium ear

Viral (most of the cases) or bacterial

Bacterial acute otitis media

Tympanus arched Liquid collection behind tympanus Otorrhea Tympanus with a yellow colour

Thickened tympanus: can be either viral or bacterial (correlate to the period of clinical evolution).

Hyperemia of tympanus inside an episode of flu is surely unlikely to be bacterial

Most common bacteria

The commonest:Streptococcus pneumoniaeHaemophilus influenzae

Others:Moraxella catarrhalisStaphylococcus aureus

-> from gut microbes:Escherichia coliPseudomonas spKlebsiella spetc.

The pneumococcus

It was sensitive to all antibiotics

Nowadays, there are a 50 to 70% of resistance to sulphas (emblematic example of inappopriate use of antibiotics)

Penicillins: in Brazil:

70 to 90% of the strains are sensitive

5 to 10% present an intermediary resistance

less than 5% with total resistance

The pneumococcusO pneumococo

Sensible to penicillin: minimum inhibitory concentration inferior to 0,06 µg/mL (which means, the seric concentration obtained by benzathine penicillin)

Intermediary: MIC of up to 2 or even 4 µg/mL: value related to seric concentration of a dose of amoxicillin

Resistant: MIC above these values

Resistance is not due to betalactamase, but to changes in the penicillin binding proteins (PBP)

The pneumococcus strains resistant to penicillin 65% resistant to sulphas 8% to eritromicin erythromycin 9% to clindamycin 2% to cephotaxime 0,8% to ofloxacin No resistance was shown to chloramphenicol,

riphampicine, vancomicine

Haemophilus

Many species: the commonest is Haemophilus influenzae

Some strains present a glycopeptidic capsule that confers a greater ability of invasion

Serogroup b: causes100% of the meningitis and the

laringites: that´s why the vaccine is against Haemophilus influenza b.

30% produce betalactamases. They can produce cephalosporinases as well

Treatment of bacterial acute otitis media 1) Try to isolate the bacteria: swab of the otorrhea, tympanocentesis,

hemoculture 2) Nasal desobstruction (frequent use of saline solution, anti-histaminics if

the patient is allergic)

3) Degree of antibiotics

Choose:

a)amoxacillin (usual dosage) b) amoxacillin in doubled dose or macrolidsc) First generation cephalosporins or betalactamase inhibitors d) Other classes

In case of interment: a)oxacillin b) Association with third generation cephalosporinc) Other classes

Duration of the treatment with antibiotics Most of the cases: after the third day, no more bacteria

are found with PCR technique

Recomendation of CDC: 7 days -> Physiologically, this is the time for the immune system creates a complete response against the agent

Cases associated with obstruction of the Eustachii tuba: at least 10 days (shorter treatments are related to early recrudescence)

Secretory otitis: minimum of 15 days

Practical discussions about prescription of antibiotics

1) Using amoxicillin in doubled dose twice a day is equally efficient as using the usual dose three times a day?

Amoxicillin BID

a) The peak of a standard dose of 500 mg of amoxicillin is the reference for defining the pneumococci of intermediary resistance

b) Even a 4-fold dose is excreted from the blood in 8 hours

Amoxicillina BID: So...

The administration of doubled dose twice a day:

a) Let the patient with no serum antibiotic for 1/3 of the day

b) Will quickly select fully resistant bacteria, as they will be exposed to higher concentrations of the antibiotics

c) Can only be indicated in ‘mild’ cases

Practical discussions about prescription of antibiotics

2) Which is better: cephalexin or clavulanate (betalactamse inhibitor)?

Cephalexin x clavulanate

Cephalexin: betalactamic resistant to betalactamases. Kills also several gram-negative bacteria

Clavulanate: inhibitor of the betalactamase of Heamophilus: limited experience in the treatment of staphylococcus

Cephalexin x clavulanate

Pharmakocinetics:

Both present tissue concentrations similar to the blood (except in liquor, due to brain hematic barrier)

Cephalexin x clavulanate

Some strains of haemophilus produce both betalactamases and cephalosporinases

These strains would be killed by clavulanate, but not by cephalexin

Costs: clavulanate: triple of cephalexin

Cephalexina x clavulanate: So...

The prohibitive cost of clavulanate and its specificity to haemophilus makes the cost/benefit ration to be more favourable to cephalexin

Bacterial acute sinusitis

Definition: infection of paranasal sinus less than 30 days.

Up to 10% of the patients with viral rhinopharingitis present bacterial sinusitis

Bacterial acute sinusitis

Main element of the clinical features: enhanced production of nasal secretion: either mucoid or purulent

Two major clinical classes of acute sinusitis:

-> Grave sinusitis: persistently high fever, intense production of mucus, intense cephalea, facial hyperemia, facial edema

-> Persistent sinusitis: good general aspect, slight or no fever, persistent production of mucus, persistent of cough or nasal obstruction, inappetence, mild cephalea, maintenance of an asthmatic crisis

Sinusitis: temporal evolution (from Wald E:

see references)

Bacterial acute sinusitis

Golden pattern for diagnosis: culture of aspirated mucus: not a simple procedure, requires specialization

Radiography: can show inespecific sinusal signs. Does not show all the facial sinus.

Signs: thickening of mucosa blurring of sinus hydroaerial levels

Tomography: presents a nice accuracy, but can not differentiate between simple virus sinusitis and bacterial ones.

X-Ray with a complete blurring of the left sinuses

Etiology of acute bacterial sinusitis

Basically, the aerophilic microbes from the rhinopharynx:

Pneumococcus

Haemophilus

Moraxella

Treatment

1) Essential: nasal desobstruction: frequent washing with saline solution, control of the allergic rhinitis

2) Antibiotics Principle: most of the persistent sinusitis will solve within 10

days. In these patients, the antibiotics reduce such time to 3-4 days

So, for mild sinusitis, 7 days is the standardSevere forms: antibiotics in higher doses and for more time (10, 15

days)

3) Corticoids: a short usage of corticoids (3-4 days) is indicated in the severe cases. The action is to quickly reduce the edema of the mucosa and hence the ammelioration in the clearance of the sinus

Conclusion

Very common Use antibiotics rationally and reasonably Re-evaluate your patients Give written information to your patiens.

References Cecil Tratado de Medicina Interna Penildon Silva Farmacologia Brasil. Ministério da Saúde. Normas para o controle e assistência das

infecções respiratórias agudas. 3ª edição, 1993. Wald E. Sinusite bacteriana aguda-protocolo da Academia Americana de

Pediatria. IV Manual de Otorrinolaringologia da IAPO. São Paulo: 2005. Almeida e cols. Consenso para o tratamento e profilaxia da influenza no Brasil.

Sociedade Brasileira de Pediatria. http://www.sbp.com.br Jefferson e cols. Inibidores da neuraminidase para prevenção e tratamento da

influenza em adultos saudáveis: revisão sistemática e metanálise. BMJ Brasil 3(21): 24-37, 2010

Lopes e cols. Perfil farmacocinético de três diferentes doses diárias de amoxicilina. Revista Brasileira de Medicina 57(1/2): 70-74, 2000.

Mantese e cols. Prevalência de sorotipos e resistência antimicrobiana de cepas invasivas de Streptococcus pneumoniae. Jornal de Pediatria 79(6): 537-542, 2003.

Pereira e cols. Prevalência de bactérias em crianças com otite média com efusão. Jornal de Pediatria 80(1):41-48, 2004

http://oradiologista.blogspot.com http://www.combustao.org/2009/02/as-10-partes-mais-inuteis-no-seu-corpo/