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Malta Medical Journal Volume 21 Issue 01 March 2009 45

Copyright Merck & Co., Inc., Whitehouse Station, NJ, USA, 2008.
All rights reserved.
0309 GRD-2008-MEA-(CY-MA)-1352-J
The one and only quadrivalent vaccine that protects against
Silgard is a vaccine for the prevention of high-grade cervical dysplasia (CIN 2/3), cervical carcinoma, high-grade vulvar dysplastic lesions (VIN 2/3),
and external genital warts (condyloma acuminata) causally related to Human Papillomavirus (HPV) types 6, 11, 16 and 18.
The indication is based on the demonstration of efficacy of Silgard in adult females 16 to 26 years of age and on the demonstration of immunogenicity
of Silgard in 9- to 15-year old children and adolescents. Protective efficacy has not been evaluated in males (see section 5.1).
ABRIDGED PRESCRIBING INFORMATION: Silgard, suspension for injection in a pre-filled syringe.Human Papillomavirus Vaccine [Types 6, 11, 16, 18] (Recombinant, adsorbed). PHARMACEUTICAL FORM: Suspension for injection in a pre-filled syringe.Prior to
agitation, Silgard may appear as a clear liquid with a white precipitate. After thorough agitation, it is a white, cloudy liquid. Therapeutic indications: Silgard is a vaccine for the prevention of high-grade cervical dysplasia (CIN 2/3), cervical carcinoma, high-grade
vulvar dysplastic lesions (VIN 2/3), and external genital warts (condyloma acuminata) causally related to Human Papillomavirus (HPV) types 6, 11, 16 and 18.The indication is based on the demonstration of efficacy of Silgard in adult females 16 to 26 years of age
and on the demonstration of immunogenicity of Silgard in 9- to 15-year old children and adolescents. Protective efficacy has not been evaluated in males (see section 5.1).The use of Silgard should be in accordance with official recommendations.Posology and
method of administration:The primary vaccination series consists of 3 separate 0.5 ml doses administered according to the following schedule: 0, 2, 6 months. If an alternate vaccination schedule is necessary, the second dose should be administered at least one
month after the first dose and the third dose should be administered at least 3 months after the second dose. All three doses should be given within a 1-year period. The need for a booster dose has not been established.Paediatric population: Silgard is not
recommended for use in children below 9 years of age due to insufficient data on immunogenicity, safety and efficacy (see section 5.1).The vaccine should be administered by intramuscular injection. The preferred site is the deltoid area of the upper arm or in the
higher anterolateral area of the thigh.Silgard must not be injected intravascularly. Subcutaneous and intradermal administration have not been studied, and therefore are not recommended (see section 6.6).Contraindications:Hypersensitivity to the active substances
or to any of the excipients. Individuals who develop symptoms indicative of hypersensitivity after receiving a dose of Silgard should not receive further doses of Silgard. Administration of Silgard should be postponed in subjects suffering from an acute severe febrile
illness. However, the presence of a minor infection, such as a mild upper respiratory tract infection or low-grade fever, is not a contraindication for immunisation.Special warnings and precautions for use: As with all injectable vaccines, appropriate medical
treatment should always be readily available in case of rare anaphylactic reactions following the administration of the vaccine.As with any vaccine, vaccination with Silgard may not result in protection in all vaccine recipients.Also, Silgard will only protect against
diseases that are caused by HPV types 6, 11, 16 and 18. Therefore, appropriate precautions against sexually transmitted diseases should continue to be used. Silgard has not been shown to have a therapeutic effect. The vaccine is therefore not indicated for treatment
of cervical cancer, high-grade cervical, vulvar and vaginal dysplastic lesions or genital warts. It is also not intended to prevent progression of other established HPV-related lesions. Vaccination is not a substitute for routine cervical screening. Since no vaccine is
100% effective and Silgard will not provide protection against non-vaccine HPV types, or against existing HPV infections, routine cervical screening remains critically important and should follow local recommendations. There are no data on the use of Silgard in
subjects with impaired immune responsiveness. Individuals with impaired immune responsiveness, whether due to the use of potent immunosuppressive therapy, a genetic defect, Human Immunodeficiency Virus (HIV) infection, or other causes, may not respond to
the vaccine. This vaccine should be given with caution to individuals with thrombocytopaenia or any coagulation disorder because bleeding may occur following an intramuscular administration in these individuals.The duration of protection is currently unknown.
Sustained protective efficacy has been observed for 4.5 years after completion of the 3-dose series. Longer term follow-up studies are ongoing (see section 5.1) Interaction with other medicinal products and other forms of interaction: In all clinical trials,
individuals who had received immunoglobulin or blood-derived products during the 6 months prior to the first vaccine dose were excluded. Use with other vaccines:Administration of Silgard at the same time (but, for injected vaccines, at a different injection site) as
hepatitis B (recombinant) vaccine did not interfere with the immune response to the HPV types. The concomitant administration of Silgard with vaccines other than hepatitis B
(recombinant) vaccine has not been studied. Use with hormonal contraceptives:In clinical studies, 57.5% of women (age 16 to 26 years) who received Silgard used hormonal
contraceptives. Use of hormonal contraceptives did not appear to affect the immune response to Silgard. Pregnancy and lactation: Specific studies of the vaccine in pregnant women
were not conducted. The data on Silgard administered during pregnancy did not indicate any safety signal. However, these data are insufficient to recommend use of Silgard during
pregnancy. Vaccination should, therefore, be postponed until after completion of pregnancy. Silgard can be given to breastfeeding women. Effects on ability to drive and use
machines: No studies on the effects on the ability to drive and use machines have been performed. Undesirable effects: Very Common: pyrexia, at the injection
site: erythema, pain, swelling. Common: At the injection site: bleeding, pruritus. Rare: urticaria. Very rare: bronchospasm. Post Marketing Experience: Post
Marketing adverse events have been spontaneously reported for Silgard and are not listed above. Gastrointestinal disorders: nausea, vomiting.Immune system
disorders: Hypersensitivity reactions including anaphylactic/anaphylactoid reactions.Nervous system disorders: dizziness, syncope.
DATE OF REVISION OF THE TEXT: July 2007
Further information is available from MSD Cyprus
Before administering Silgard

, please read the Physician Circular.


SILGARD

is a registered trademark of Merck & Co., Inc., Whitehouse Station, NJ, USA.
Now is the time to vaccinate 9-15 year old children and 16-26 year old females
CERVICAL CANCER
HIGH GRADE VULVAR DYSPLASTIC LESION
CERVICAL DYSPLASIA
GENITAL WARTS
Announcing a new era in vaccination
caused by Human Papillomavirus Types 6, 11, 16, and 18.
Abstract
Acute bronchitis is a common respiratory tract infection
usually caused by viruses and encountered often by family
doctors. Diagnosis is usually made on clinical symptoms,
as fndings on physical examination are usually limited and
investigations give non-specifc results. Numerous studies
have shown that antimicrobial agents are useless in acute
bronchitis, and have a negligible effect on symptoms. The
use of other medications such as
2
-agonists and cough
suppressants has also been questioned and these medications
are usually reserved for patients suffering from chronic lung
conditions. Delayed prescription has been considered as a
means of reducing antibiotic overprescribing in respiratory tract
infections, however, the effect of such measures on antibiotic
use and resolution of symptoms is questionable, as are studies
on the patients satisfaction with delayed prescribing. Patients
knowledge on respiratory tract infections and their treatment
must also be considered, as it has been shown that family
practitioners should be aware of the patients expectations when
they attend with a respiratory tract infection.
Introduction
Acute bronchitis is a self-limited infammation of the large
airways of the lungs. It affects approximately 5% of adults
annually, with a higher incidence observed during winter and
autumn rather than in summer and spring.
1,2
Acute bronchitis
represents almost 20% of respiratory tract infections with an
incidence of around 29 episodes per thousand person years.
3
In children, 5% of visits to the family doctor are for acute
bronchitis, representing around 12% of visits for respiratory
tract infections.
4,5
On the other hand, in adults, acute bronchitis
comprises 23% of respiratory tract infections encountered by
family doctors.
6
A typical clinical scenario
A 34 year-old male presented with a three day history of
increasing cough, progressing from a dry one, to one producing
yellowish sputum. He also complained of night-time low-
grade fever which was relieved with paracetamol. The patient
confrmed mild shortness of breath on exertion but denied chest
pain. He did not suffer from asthma and had quit smoking ten
years previously. On examination, the patient was afebrile
and auscultation of the chest disclosed faint wheezing on
expiration.
Aetiology
Viruses are the most common cause of acute bronchitis: the
main culprits being infuenza A and B viruses, parainfuenza
virus, respiratory syncytial virus, coronavirus, adenovirus
and rhinovirus.
7
Bacterial species commonly implicated in
community-acquired pneumonias are also isolated from the
sputum in a minority of patients suffering from acute bronchitis.
1

These include Streptococcus pneumoniae, Haemophilus
infuenzae and Moraxella catharralis.
8
However, the role of
these species in the disease remains unclear as bronchial biopsies
have not shown bacterial invasion. In some cases, atypical
bacteria such as Bordetella pertussis, Chlamydia pneumoniae
and Mycoplasma pneumoniae may be implicated.
1
Clinical presentation
Management of acute bronchitis in the community is very
much dependent on comprehensive history taking and a high
index of suspicion.
Bjorn Buhagiar MD
Department of Primary Health Care, Floriana
Email: bjornbuh@maltanet.net
Keywords
Acute bronchitis, antimicrobials, delayed prescriptions,
patient expectations
Bjorn Buhagiar
In Practice
Acute Bronchitis
46 Malta Medical Journal Volume 21 Issue 01 March 2009
Signs and symptoms
During the frst few days of the infection, the symptoms of
acute bronchitis cannot be distinguished from those of a mild
upper respiratory tract infection. However, in the case of acute
bronchitis the cough persists for more than 5 days, usually for 10
to 20 days, although occasionally it may last for 4 or more weeks.
This cough is usually dry but some patients may report the
production of sputum. Fever, fatigue and malaise may feature
together with the cough and more severe symptoms include
shortness of breath, wheezing and chest pains. Infections by
adenoviridae might also cause gastrointestinal symptoms.
9
Examination in patients with acute bronchitis is usually
normal however in severe cases, there may be a rise in
temperature and signs of respiratory distress. Chest examination
can reveal decreased intensity of breath sounds, wheezing,
rhonchi and prolonged expiration.
9

Investigations
Diagnosis of acute bronchitis is usually made from the
clinical history and by exclusion of the presence of pneumonia.
Most family doctors rely on the presence of a persistent dry or
productive cough. A chest X-ray can reveal hyperinfation whilst
a full blood count would feature a raised white blood cell count. A
sputum sample may disclose increased neutrophils and a culture
may grow an organism, when the cause is bacterial.
Treatment
Antimicrobial therapy
Antibiotics are not recommended in most cases of acute
bronchitis. Systematic analyses of clinical trials have suggested
that antimicrobial agents may reduce the duration of symptoms
only slightly. A quantitative systemic review showed that
resolution of cough was not affected by antibiotic treatment
and neither was there any signifcant clinical improvement. The
side-effects of antibiotics were predictably more common in the
antibiotic groups than in the placebo groups.
9
A meta-analysis of
eight trials showed that the use of antibiotics in acute bronchitis
reduced the duration of cough and sputum production by
one and a half days. The results were statistically signifcant,
however, one can argue that the risk of side-effects and the
societal cost of increasing antibiotic resistance need to be taken
into consideration when interpreting such fndings.
10

Results of a randomised, double-blind trial comparing
patients suffering with acute bronchitis treated with azithromycin
with those treated with vitamin C showed no difference between
the groups in the health-related quality of life at seven days or in
the proportion of patients who returned to work, school or usual
activities at home on day three or seven.
11
A Cochrane review of
nine randomised, controlled trials of antibiotic agents showed a
signifcant but minor reduction in the duration of cough. There
was a non-signifcant reduction in the number of days of feeling
ill and a non-signifcant increase in adverse events attributed
to antibiotics.
12

Antibiotics are indicated for acute bronchitis when bacteria
are cultivated from sputum cultures. Admittedly, sputum
culture for bacteria is infrequently done at community level,
since the results of such procedure take time, and as previously
highlighted, do not have a particularly relevant role in the
management of the patients condition. Clinical symptoms
that indicate the presence of a bacterial infection would be
production of greenish sputum and the presence of high fever.
If antibiotic treatment is deemed necessary, the medications of
choice are co-amoxiclav, and clarithromycin in patients allergic
to penicillin.
8
Other treatment
A few randomised controlled trials have studied the effect
of
2
-agonists administered orally or by aerosol for cough
associated with acute bronchitis. All these trials have involved
a small number of patients and produced mixed results. Most
trials involved patients without preexisting lung disease and
showed that daily cough scores and the likelihood of persistent
cough after seven days did not differ signifcantly between
the active treatment and placebo groups.
13-15
However, in one
trial, a subgroup of patients with evidence of airfow limitation
had signifcantly lower scores for symptoms on day two after
treatment with
2
-agonists.
13
A recent Cochrane Review of fve
trials involving 418 adults showed that even among patients
with airfow obstruction, the potential beneft of
2
-agonists is
not well supported and should be balanced against the adverse
effects of treatment.
16
Although there are multiple clinical trial data on the use of
mucolytics and oral steroids in chronic bronchitis, there is no
data that supports the use of these agents in the treatment of
acute bronchitis.
Guidelines
According to the 2001 guidelines of the American College of
Physicians for the treatment of uncomplicated acute bronchitis,
antibiotic treatment is not recommended, regardless of the
duration of cough.
17
According to the 2006 guidelines of the
American College of Chest Physicians (ACCP), routine treatment
with antibiotics for treating acute bronchitis is not justifed. They
also suggest that antitussive agents are only occasionally useful
and that there is no routine role for inhaled bronchodilators or
mucolytic agents. However, these guidelines note that subgroups
of patients with chronic airflow obstruction at baseline or
wheezing at the onset of illness may beneft from beta2-agonists.
These guidelines have been criticised on the grounds that many
of the recommendations were based more on opinion rather
than on evidence.
Delayed prescriptions
Delayed prescription is when the family doctor prescribes
a medicine and advises the patient to take medication after
a number of days, only if certain signs or symptoms persist
or develop. This can potentially address both the patients
expectation of an antibiotic prescription and the practitioners
clinical uncertainty, while minimising actual antibiotic
consumption.
Malta Medical Journal Volume 21 Issue 01 March 2009 47
Antibiotic overprescribing
The use of delayed prescription to reduce antibiotic
overprescribing in acute bronchitis and other respiratory
tract infections has been considered in several studies. The
first evidence of benefit from delayed prescribing using a
randomised controlled trial came from a 1997 study involving
patients complaining of a sore throat. This showed that 99% of
the immediate prescriptions were consumed whilst only 31%
of delayed prescriptions were consumed without apparent
serious harm.
19
Other studies showed that delayed prescriptions
resulted in reduced antibiotic prescription also in patients with
otitis media, in those with cough, and in patients with common
cold.
20-23
Three of these studies reported an increase in signs and
symptoms in patients who received a delayed prescription
19,20,22
,
one study reported a decrease in symptoms
23
whilst the other
study did not report anything on symptoms.
21

Satisfaction with the consultation
and beliefs on delayed prescription
Little is known about patients response to delayed
prescribing, or the decision-taking processes that they employ
in choosing whether to take their medication. The satisfaction
of the patient with delayed prescribing was also studied in the
studies mentioned above. Two of the randomised trials showed
a signifcant decrease in satisfaction with the consultation when
delayed antibiotics were given.
20,22
Two studies reported good
patient satisfaction but this was not statistically signifcant.
19,23
Moreover, two of the studies showed that patients were less
convinced that delayed prescriptions were more effective than
immediate prescription.
19,21

In contrast, in a study on patients responses to delayed
prescription it was found that around half of the patients that
were prescribed a delayed antibiotic for a respiratory tract
infection, actually took the medication. Eighty-seven percent
of these people reported that they were confdent taking the
decision whether to take the prescribed antibiotic, and more
than 90% would have chosen a delayed prescription again.
24

Patients expectations
Not all patients are aware that most respiratory tract
infections, including acute bronchitis, are caused by viruses and
many patients have misconceptions on the use of antibiotics
for such infections.
25-27
In fact, many patients would expect
an antibiotic for their infection, though less would request a
prescription. Many of such patients would base their satisfaction
on the prescription of the antibiotic.
26
The situation with children
is different, in that parents are being increasingly concerned
about the excessive amount of antibiotics their children were
being prescribed.
28

The association between receiving antibiotics and
information/reassurance on the one hand, and patients
satisfaction on the other, among patients with acute respiratory
tract symptoms has also been studied. It was found that 90% of
patients expected reassurance or information and most of these
patients received it. Half of the patients expected an antibiotic
and more than 70% of these received one. They also reported
that receiving information or reassurance was more strongly
associated with patient satisfaction rather than being prescribed
an antibiotic.
29

Conclusion
The patient presented in this clinical scenario was not
prescribed any antibiotics as there were no clinical features
suggestive of bacterial aetiology. Instead, the patients
expectations from the consultation were explored. He stated
that he had decided to consult a doctor as he was worried
that he might be getting a bad infection. It was subsequently
explained that the bronchitis was probably being caused by a
virus and the natural course of the infection was discussed. He
was reassured that no antibiotics were required but paracetamol
was prescribed to relieve symptoms. He was also prescribed
a short-acting bronchodilator for a brief period to relieve the
shortness of breath. An opportunity was taken to discuss the
issue of smoking with the patient. Instead of offering a delayed
prescription, the patient was advised to attend again if symptoms
were to deteriorate or if the cough would persist for more than
three weeks.
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