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| Fonte:lillingtonmedicalservices.org |
Uma revisão da Cochrane, atualizada no início de 2014, reforça conhecimento de que antibióticos não devem ser utilizados em pessoas com sintomas de resfriado simples nem mesmo com rinorreia purulenta de menos de 10 dias.
Não só não houve melhora do quadro e sintomas quando comparado com placebo, como houve, de forma estatisticamente significante, mais efeitos colaterais causados pelos antibióticos como náuseas, dores abdominais, diarreia e reações alérgicas, entre outros. Sem falar na possibilidade de indução de resistência bacteriana.
A publicação segue como mais um reforço ao uso judicioso e criterioso de antimicrobianos e para seguimento do primum non nocere (não maleficência).
Entretanto, lembremos que os pacientes muitas vezes podem vir com um modelo de doença prévio que está arraigado na sua mente de que os antibióticos provavelmente melhorarão seu quadro. Como resolver esse conflito? Algumas coisas podem ser importantes como: 1) Não desprezar a queixa principal 2) Utilizar de tempo para explicar e tentar construir um novo modelo de doença e 3) talvez mais importante e difícil, garantir acessibilidade para reavaliação de acordo com evolução do caso.
Não esquecer que, como sempre, nós somos responsáveis pela medicina que nós e nossos colegas praticam. A "falta de tempo" em educar o paciente, perpetua esse modelo em que todos reclamamos, mas, em última análise, comparticipamos.
Para ver a revisão da Cochrane completa, clique abaixo:
Para ver a revisão da Cochrane completa, clique abaixo:
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COCHRANE VHL
Antibiotics for the common cold and acute purulent rhinitis
Kenealy Tim, Arroll Bruce
Cochrane Database of Systematic Reviews, Issue 2, 2014 (Status in this issue: NEW SEARCH FOR STUDIES AND CONTENT UPDATED (NO CHANGE TO CONCLUSIONS))
Copyright © 2009 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
DOI: 10.1002/14651858.CD000247.pub4
Abstract
Background
It has long been believed that antibiotics have no role in the treatment of common colds yet they are often prescribed in the belief that they may prevent secondary bacterial infections.
Objective
To determine the efficacy of antibiotics compared with placebo for reducing general and specific nasopharyngeal symptoms of acute upper respiratory tract infections (URTIs) (common colds).
To determine if antibiotics have any influence on the outcomes for acute purulent rhinitis and acute clear rhinitis lasting less than 10 days before the intervention.
To determine whether there are significant adverse outcomes associated with antibiotic therapy for participants with a clinical diagnosis of acute URTI or acute purulent rhinitis.
To determine if antibiotics have any influence on the outcomes for acute purulent rhinitis and acute clear rhinitis lasting less than 10 days before the intervention.
To determine whether there are significant adverse outcomes associated with antibiotic therapy for participants with a clinical diagnosis of acute URTI or acute purulent rhinitis.
REVIEW_ABS_OTHER
For this 2013 update we searched CENTRAL 2013, Issue 1, MEDLINE (March 2005 to February week 2, 2013), EMBASE (January 2010 to February 2013), CINAHL (2005 to February 2013), LILACS (2005 to February 2013) and Biosis Previews (2005 to February 2013).
Selection criteria
Randomised controlled trials (RCTs) comparing any antibiotic therapy against placebo in people with symptoms of acute upper respiratory tract infection for less than seven days, or acute purulent rhinitis less than 10 days in duration.
Data collection and analysis
Both review authors independently assessed trial quality and extracted data.
Main results
This updated review included 11 studies. Six studies contributed to one or more analyses related to the common cold, with up to 1047 participants. Five studies contributed to one or more analyses relating to purulent rhinitis, with up to 791 participants. One study contributed only to data on adverse events and one met the inclusion criteria but reported only summary statistics without providing any numerical data that could be included in the meta-analyses. Interpretation of the combined data is limited because some studies included only children, or only adults, or only males; a wide range of antibiotics were used and outcomes were measured in different ways. There was a moderate risk of bias because of unreported methods details or because an unknown number of participants were likely to have chest or sinus infections.
Authors' conclusions
There is no evidence of benefit from antibiotics for the common cold or for persisting acute purulent rhinitis in children or adults. There is evidence that antibiotics cause significant adverse effects in adults when given for the common cold and in all ages when given for acute purulent rhinitis. Routine use of antibiotics for these conditions is not recommended.
Plain language summary
Most people around the world will have one or more common cold episodes every year. Except in low-income countries, the common cold is one of the most cited reasons for people to use antibiotics, even more so if the mucus from their nose is coloured (acute purulent rhinitis). However, common colds are caused by viruses, which do not respond to antibiotics, and antibiotics can cause side effects, especially diarrhoea. Overuse of antibiotics leads to bacteria becoming resistant to antibiotics.
To find out whether antibiotics work for the common cold we identified studies that compared one group of people taking an antibiotic with another group of people taking a medication that looked similar but contained no antibiotic (a placebo). We found six studies of the common cold, with 1047 participants and five studies of acute purulent rhinitis, with 791 participants. Many of the studies had flaws which might have biased the results, especially because many of the participants probably had chest or sinus infections that the researchers did not know about.
Results suggest that antibiotics do not work for either the common cold or for acute purulent rhinitis and many people are affected by antibiotic side effects.
What's new
What's new
Last assessed as up-to-date: 26 February 2013.
| Date | Event | Description |
|---|---|---|
| 26 February 2013 | New search has been performed | Searches conducted. We found no new trials. Numbers from the De Sutter 2002 trial with the outcome of persistent purulent rhinitis were corrected. |
| 26 February 2013 | New citation required but conclusions have not changed | There is no substantive change in the statistical results. Our conclusions remain unchanged. |
Background
The International Classification of Health Problems in Primary Care (ICHPPC) ( Spector 1995 ) defines an acute upper respiratory tract infection (URTI), the common cold, as an illness with evidence of acute inflammation of the nasal or pharyngeal mucosa and the absence of other specifically defined respiratory conditions, for example streptococcal tonsillitis, laryngitis, bronchitis, pneumonia, asthma and hay fever ( ICHPPC 1986 ). A common cold is commonly regarded as a self limiting viral illness that is experienced annually by the majority of the population. A practical definition is an acute illness with some of the following symptoms: rhinitis (not hay fever or allergic rhinitis), sore throat (not streptococcal pharyngitis), with or without fever, cough and/or productive sputum/purulent sputum.
There is evidence of high usage of antibiotics for the common cold (viral URTI) in spite of doubts about the efficacy of such therapy ( McGregor 1995 ; Spector 1995 ). Although it is known that viruses are the causative agent, many patients presenting to their general practitioners receive antibiotics. In one study, URTI was the most common reason for new consultations in general practice and the second most common reason for the prescribing of an antibiotic ( McAvoy 1994 ). In a New Zealand study, computerised records of 100,222 consultations from 17 General Practices were examined over one year ( McGregor 1995 ). Seventy-eight per cent of patients with an URTI received antibiotics. About one-third of these medications were expensive broad-spectrum antibiotics. In a more recent study, 49% of persons with URTIs received antibiotics ( Ochoa 2000 ).
There are two published reviews of antibiotics for treating URTIs. One review found no benefit of antibiotics for preventing pneumonia in patients with URTI ( Gadomski 1993 ). Another review found that antibiotics had no benefit in children and that there was no strong evidence of significant adverse effects ( Fahey 1998 ).
The presence of purulent nasal discharge (or a runny nose with coloured discharge) has repeatedly been shown to be an important determinant of antibiotic prescribing for respiratory tract infections for both adults and children ( Arroll 2000 ; Gonzales 1999 ; Mainous 1997 ). In one study, no General Practitioners said they would give antibiotics for clear rhinitis, yet 72% said they would for purulent rhinitis ( Arroll 2000 ). A survey found that primary care physicians were far more likely to prescribe an antibiotic for a patient with a cold involving coloured nasal discharge than for a patient without coloured nasal discharge ( Mainous 1997 ). Another study found purulent nasal discharge was a stronger predictor of prescribing antibiotics than any other patient characteristic ( Gonzales 1999 ).
Guidelines usually advise against antibiotics for acute purulent rhinitis ( Rosenstein 1998 ; Snow 2001 ) yet evidence supporting such recommendations comes from a limited number of small studies of varying methodological quality. Some studies have found no evidence that antibiotics reduce the duration of acute purulent rhinitis ( Todd 1984 ) whereas a recent larger study reported that treatment with amoxicillin reduced the duration of purulent rhinorrhoea; although there was no significant difference between the groups in terms of general symptom improvement ( De Sutter 2002 ).
It is important to obtain an estimate of the effectiveness of antibiotics for the common cold to support judicious use of these important medicines, particularly because URTIs are so common. If ineffective, as has long been thought, widespread use of antibiotics is not only a poor use of health funds but also a cause of unnecessary morbidity from adverse effects and of development of resistant strains ( Arason 1996 ; Verkatesum 1995 ). If antibiotics were shown to be effective for the common cold then society may be willing to tolerate the increase of resistance with an appropriate reduction in the symptoms. Other reviews to date have not specifically considered the effect of antibiotics in acute purulent rhinitis. The current review expands on previous reviews by considering the effects of antibiotics on the speed of resolution of common cold symptoms in both adults and children, and by examining the evidence for antibiotics in both acute purulent rhinitis and acute clear rhinitis.
Objectives
To determine the efficacy of antibiotics compared with placebo for reducing general and specific nasopharyngeal symptoms of acute URTIs (common colds).
To determine if antibiotics have any influence on the outcomes for acute purulent rhinitis and acute clear rhinitis lasting less than 10 days before the intervention.
To determine whether there are significant adverse outcomes associated with antibiotic therapy for participants with a clinical diagnosis of acute URTI or acute purulent rhinitis.
Methods of the review
Criteria for considering studies for this review
Types of studies
All trials in which participants with the diagnosis of acute upper respiratory tract infection (URTI) were randomly assigned to treatment with an antibiotic or a placebo; also all trials in which the majority of participants had acute purulent rhinitis of less than 10 days duration. We included trials allowing concurrent use of other medications if they allowed equal access for participants in both the antibiotic and placebo group.
We excluded studies for the following reasons.
If they involved the use of an active substance (such as cough mixtures or anti-pyretics/analgesics) instead of a placebo as these substances may help or suppress symptoms, thereby giving a false measure of the antibiotic's effectiveness. Trials comparing one antibiotic with another, or trials comparing the use of antibiotics versus other medications, were not included.
If antibiotics were given prophylactically, that is given to asymptomatic individuals, for many weeks to prevent symptoms of acute URTI.
If more than 5% of participants had throat swabs positive for beta haemolytic streptococcal infection. In the sore throat review by Del Mar 1992 , the lowest percentage of participants with streptococci on throat swab was 8%, hence our choice of 5%. Two studies ( Haight 1954 ; Hardy 1956 ) were excluded by this criterion but neither had data that could be analysed. We accept the contradiction that some studies may include participants with streptococcal infections or colonisation due to the fact that they have not performed throat cultures. There is also the issue of contaminants, which may be as high as 57% in children under 15 years with pharyngitis ( Kaplan 1971 ), hence our desire to remove studies with high proportions of participants with positive throat cultures.
If not randomised.
If participants had past histories of serious illness, for example chronic obstructive respiratory disease where antibiotics have been shown to be effective in treating exacerbations.
If the participants had been given the diagnosis of bronchitis. The International Classification of Health Problems in Primary Care (ICHPPC) definition of bronchitis ( Spector 1995 ) is a definite cough with abnormal chest signs: scattered or generalised, coarse or moist sounds, or wheeze. This definition is not always used by trialists and probably not by General Practitioners ( Arroll 2001 ).
If the participants had more than seven days of symptoms at the time of study entry. This is an arbitrary duration to avoid post viral syndromes.
If participants were treated with two or more medications, that is in situations where co-interventions could be an issue.
If participants were diagnosed with pharyngitis not conforming to the ICHPPC ( Spector 1995 ).
If they did not include a placebo arm.
Types of participants
The analysis of the effect of antibiotics on general symptoms of the common cold included participants of all ages who had been diagnosed with an acute URTI and had symptoms for seven days or less. We excluded trials in which the majority of participants had been diagnosed with pharyngitis or bronchitis conforming to the International Classification of Health Problems in Primary Care ( ICHPPC 1986 ) definition. Lower respiratory tract signs were accepted in participants with the above symptoms, so long as the majority of participants in the study did not have these signs and pneumonia was ruled out.
Types of intervention
Antibiotic therapy versus placebo. We included trials which allowed concurrent use of other medications if they allowed equal access for participants in both the antibiotic and placebo group. We excluded studies if they did not compare antibiotic with placebo but instead used aspirin or antitussives in the control group.
Types of outcome measures
The outcome measures included persistence of symptoms of nasopharyngeal inflammation (rhinitis, sore throat and sneezing), global rating of health and any adverse effects.
Primary outcomes
For the common cold: persisting symptoms.
For acute purulent rhinitis: persistent purulent rhinitis.
Secondary outcomes
For both the common cold and acute purulent rhinitis: adverse effects.
For the common cold: sore throat, loss of time at work, loss of appetite, sneezing.
For purulent rhinitis: persisting purulent rhinitis on currently available medication.
Search methods for identification of studies
Search methods for identification of studies
Electronic searches
For this 2013 update we searched the Cochrane Central Register of Controlled Trials (CENTRAL) 2013, Issue 1, part of The Cochrane Library, www.thecochranelibrary.com (accessed 26 March 2013), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (March 2005 to February 2013), EMBASE (January 2010 to February 2013), CINAHL (2005 to February 2013), LILACS (2005 to February 2013) and Biosis Previews (2005 to February 2013).
We used the following search strategy to search MEDLINE and CENTRAL. We combined the MEDLINE search strategy with the Cochrane Highly Sensitive Search Strategy for identifying randomised trials in MEDLINE: sensitivity- and precision-maximising version (2008 revision); Ovid format ( Lefebvre 2011 ). We adapted this search strategy to search EMBASE ( Appendix 1 ), CINAHL ( Appendix 2 ), LILACS ( Appendix 3 ) and Biosis Previews ( Appendix 4 ). The search strategy has been amended since the last published version as the authors have now extended the review to include persistent nasal discharge (rhinosinusitis). Details of earlier searches are in Appendix 5 .
MEDLINE (Ovid)
1 Respiratory Tract Infections/
2 (upper adj3 respiratory tract infection*).tw.
3 (upper adj3 respiratory infection*).tw.
4 urti.tw.
5 Common Cold/
6 common cold*.tw.
7 head cold*.tw.
8 coryza.tw.
9 Rhinitis/
10 rhinit*.tw.
11 rhinosinusit*.tw.
12 nasosinusit*.tw.
13 (rhinorrhoea or rhinorrhoea).tw.
14 Nasal Obstruction/
15 ((runny or running or discharg* or congest* or blocked or stuff* or dripping) adj2 (nose* or nasal)).tw.
16 pharyngitis/ or nasopharyngitis/
17 (pharyngit* or nasopharyngit*).tw.
18 rhinopharyngit*.tw.
19 Paranasal Sinus Diseases/
20 exp Sinusitis/
21 sinusit*.tw.
22 exp Laryngitis/
23 laryngit*.tw.
24 sore throat*.tw.
25 or/1-24
26 exp Anti-Bacterial Agents/
27 antibiotic*.tw,nm.
28 (amoxicillin* or amoxycillin* or ampicillin* or penicillin* or tetracycline* or erythromycin* or oxytetracycline* or azithromycin* or ciprofloxacin* or pivampicillin* or cefuroxime* or augmentin* or co-trimoxazole* or cefoxitin* or ceftriaxone* or cefixime* or norfloxacin* or ceftazidime* or cefaclor* or ofloxacin*).tw,nm.
29 exp Sulfamethoxazole/
30 (sulphamethoxazole or sulfamethoxazole or sulfisoxazole).tw,nm.
31 or/26-30
32 25 and 31
2 (upper adj3 respiratory tract infection*).tw.
3 (upper adj3 respiratory infection*).tw.
4 urti.tw.
5 Common Cold/
6 common cold*.tw.
7 head cold*.tw.
8 coryza.tw.
9 Rhinitis/
10 rhinit*.tw.
11 rhinosinusit*.tw.
12 nasosinusit*.tw.
13 (rhinorrhoea or rhinorrhoea).tw.
14 Nasal Obstruction/
15 ((runny or running or discharg* or congest* or blocked or stuff* or dripping) adj2 (nose* or nasal)).tw.
16 pharyngitis/ or nasopharyngitis/
17 (pharyngit* or nasopharyngit*).tw.
18 rhinopharyngit*.tw.
19 Paranasal Sinus Diseases/
20 exp Sinusitis/
21 sinusit*.tw.
22 exp Laryngitis/
23 laryngit*.tw.
24 sore throat*.tw.
25 or/1-24
26 exp Anti-Bacterial Agents/
27 antibiotic*.tw,nm.
28 (amoxicillin* or amoxycillin* or ampicillin* or penicillin* or tetracycline* or erythromycin* or oxytetracycline* or azithromycin* or ciprofloxacin* or pivampicillin* or cefuroxime* or augmentin* or co-trimoxazole* or cefoxitin* or ceftriaxone* or cefixime* or norfloxacin* or ceftazidime* or cefaclor* or ofloxacin*).tw,nm.
29 exp Sulfamethoxazole/
30 (sulphamethoxazole or sulfamethoxazole or sulfisoxazole).tw,nm.
31 or/26-30
32 25 and 31
Searching other resources
We wrote to the trial authors of all the included studies and asked them if they knew of any unpublished material. We did not find any additional papers by this mechanism.
Data collection and analysis
Data collection and analysis
Selection of studies
The two review authors (BA, TK) independently checked the abstracts from the searches and selected the papers. We resolved disagreements through discussion. The Herne 1980 trial was translated from French to English. One paper was excluded because a placebo was not used in the control group ( Sutrisna 1991 ).
Data extraction and management
The two review authors (BA, TK) selected the relevant abstracts after the full papers were obtained. The two review authors (BA, TK) independently extracted data and we resolved disagreements through discussion.
Assessment of risk of bias in included studies
We used the Cochrane 'Risk of bias' tool for assessing bias ( Higgins 2011 ) with consideration of: adequate sequence generation, concealment of allocation, adequate blinding, incomplete outcome reporting and freedom from selective reporting. The two review authors (BA, TK) independently assessed trial quality and any differences were resolved through discussion.
Measures of treatment effect
We used the risk ratio (RR) exclusively for dichotomous data.
Unit of analysis issues
All trials were standard parallel design randomised controlled trials (RCTs). The individual patient was the unit of analysis.
Dealing with missing data
None of the trials in this review except De Sutter 2002 conducted an intention-to-treat (ITT) analysis. All our results are per protocol analyses.
Assessment of heterogeneity
We assessed heterogeneity using the I2 statistic. When the I2 statistic was over 50% we changed the analysis from fixed-effect to random-effects.
Assessment of reporting biases
The majority of our studies were negative and this, to some extent, guards against publication bias. The one positive study may have included participants with bacterial conditions such as streptococcal tonsillitis.
Data synthesis
We conducted a meta-analysis using the Review Manager ( RevMan 2012 ) software.
Subgroup analysis and investigation of heterogeneity
There was no subgroup analysis.
Sensitivity analysis
We conducted a sensitivity analysis on the main analysis of persisting symptoms and omitted the trial by Herne 1980 . This changed the I2 statistic from 54% to 0%. The Herne trial was the outlier in that it was the only statistically significant trial in the common cold section of the review and may have contained participants with streptococcal tonsillitis. We conducted another sensitivity analysis with the adverse effects for all the trials. This showed a statistically significant result in adults but not in children. The other sensitivity analysis was in the persistent purulent rhinitis outcome where the Herne trial was added for both clear and purulent rhinitis. When the Herne trial was added as purulent, the reduction in symptoms was just statistically significant. This did not change the conclusions.
Methodological quality
Results
Results
Description of studies
Results of the search
See Appendix 2 for details of previous searches. In the 2009 search we identified 545 papers. None of them met the inclusion criteria for this review. The 2013 search of the electronic resources retrieved 1128 records.
Included studies
Types of participants
Ten studies contributed data to the meta-analyses. A further trial ( Gordon 1974 ) reported only summary statistics, without providing any numerical data that could be included in the meta-analyses. Six studies contributed to one or more analyses of common cold outcomes (up to 1047 participants) and five contributed to one or more analyses of purulent rhinitis outcomes (up to 791 participants). Two contributed to both ( Herne 1980 ; Taylor 1977 ). One study contributed to the adverse effects but did not contribute to the other outcome data ( Howie 1970 ). Four of the trials in this review included children only ( Gordon 1974 ; Lexomboon 1971 ; Taylor 1977 ; Todd 1984 ). Vogt 1966 included participants recruited from paediatricians' offices, so there is an implication that these were all children. The remaining studies included:
adolescents and adults with no upper limit of age ( Herne 1980 ; Hoaglund 1950 ; Kaiser 1996 );
males aged 20 to 49 years ( Howie 1970 ); and
adults up to 69 years ( McKerrow 1961 ).
Three studies examined men only ( Herne 1980 ; Hoaglund 1950 ; Howie 1970 ).
Types of outcome measures
Only four studies measured the effect of antibiotics on symptoms ( Herne 1980 ; Howie 1970 ; Taylor 1977 ; Todd 1984 ). The denominator for one of these, Howie 1970 , was episodes of illness rather than the number of participants, which prevented these data from being pooled with other studies. However, adverse effects in this study were based on individuals, hence adverse effects reported have been added to those from other studies (except for outcomes from five participants who had adverse effects with more than one course of antibiotics and were removed from the analysis).
Types of interventions
Antibiotics used included:
a form of tetracycline, in five studies ( Herne 1980 ; Hoaglund 1950 ; Howie 1970 ; Lexomboon 1971 ; McKerrow 1961 );
penicillin, ampicillin and amoxicillin, and amoxicillin/clavulanic acid, in five studies ( De Sutter 2002 ; Gordon 1974 ; Kaiser 1996 ; Lexomboon 1971 ; Taylor 1977 );
erythromycin, in one study ( Gordon 1974 );
co-trimoxazole, in one study ( Taylor 1977 );
cephalosporin, in one study ( Todd 1984 );
an antibacterial called xibornol (no longer on the market in France or elsewhere) in one study ( Herne 1980 ) and also mentioned by Reynolds 1996 ; and
topical nitrofurazone, in one study ( Vogt 1966 ).
Nasopharyngeal cultures
Kaiser 1996 performed an analysis by culture status of three nasopharyngeal pathogens: Haemophilus influenzae (H. influenzae),Moraxella catarrhalis (M. catarrhalis) and Streptococcus pneumoniae (S. pneumoniae). The only trial to do throat swabs on almost all (88 out of 89) participants was Gordon 1974 . These participants were included in the analysis. Herne 1980 excluded some participants from the analysis because they developed a red, pustular tonsillitis thought to be due to beta haemolytic streptococcus.
Inclusion criteria
The inclusion criteria were either contained in the methods section or in the title of the study. They were:
in Gordon 1974 , participants with minor respiratory illness (in the title) and symptoms referable to the respiratory tract, not sick enough for the use of a placebo to be a risk;
in Herne 1980 , non-severe upper respiratory tract infection (in the methods);
in Hoaglund 1950 , common cold (in the title) and local and constitutional symptoms (in the methods);
in Howie 1970 , minor respiratory illness (in the title) and presence of cough, spit, purulent spit and purulent nasal discharge;
in Kaiser 1996 , common cold (in the title) and symptoms of nasal congestion and rhinorrhoea (in the methods);
in Lexomboon 1971 , upper respiratory tract infection (URTI) (in the title) and symptoms of URTI within the last 48 hours (in the methods);
in McKerrow 1961 common cold (in the title);
in Taylor 1977 participants with presumed viral respiratory infection (in the title) and exclusion of participants with beta haemolytic streptococcus on throat swabs, otitis media and pneumonia;
in Todd 1984 , non-transparent anterior nasal discharge (in the methods section).
Two included studies ( De Sutter 2002 ; Vogt 1966 ) focused on acute purulent rhinitis.
Excluded studies
We excluded 31 studies. The major reason for exclusion was that they were not placebo-controlled (usually compared to another antibiotic or an over-the-counter medication). There were also a number of trials conducted in the military which used prophylactic antibiotics.
Risk of bias in included studies
All of the included trials were double-blind evaluations comparing antibiotic with a placebo. It was assumed that blinding was satisfactory because all studies included a statement that medication was given in a double-blind manner and un-blinding of participants was not reported. However, no formal description of blinding was included in any of the trials.
The method of randomisation was marginally satisfactory for some of the studies. In Hoaglund 1950 the pharmacist dispensed the medication "in rotation". The method of randomisation was "haphazard" in the study by Vogt 1966 , hence there is some concern about the methods of this study. In Lexomboon 1971 the allocation was determined by the selection of coloured strips and only the pharmacist knew the allocation. The method of randomisation for the De Sutter 2002 study was by computer-generated random number and the medications (capsules) were identical.
All but two of the studies had either inclusion criteria that selected cases of acute viral respiratory tract infection and/or had the term viral or minor respiratory infection or common cold in the title of the study. The exception was Todd 1984 , where the children had non-transparent nasal discharge. While there was some variation in the inclusion criteria (for example, Gordon 1974 found 13% of children under two years old and 16% of two- to four-year olds had clinical signs in the chest) the study groups generally included participants with acute URTIs. There were no extractable data in this study so the results were not pooled.
Loss to follow-up was an issue for a number of the studies; only one analysed results on an ITT basis ( De Sutter 2002 ).
The overall risk of bias is presented graphically in and summarised in .
Allocation
There was a range of different methods of randomisation. They ranged from computerised randomisation ( De Sutter 2002 ), randomised and no details ( Herne 1980 ), dispensed in rotation by the pharmacist ( Hoaglund 1950 ), and random selection of coloured strips from a box (only the pharmacists knew the allocation) ( Lexomboon 1971 ).
Blinding
All trials had identical active and placebo medications.
Incomplete outcome data
The drop-out rate ranged from 0% ( Gordon 1974 ; Hoaglund 1950 ) to 25% ( Todd 1984 ). There do not seem to be any differential drop-out rates so it is unlikely that this would affect the outcomes.
Selective reporting
There was no evidence of selective reporting.
Other potential sources of bias
The potential for bias in a trial of a predominantly viral condition is that of bacterial co-morbidity. In the De Sutter 2002 trial more then 60% of the participants had facial pain and some of these may have had bacterial sinusitis. In the study by Herne 1980 there were a number of participants with streptococcal tonsillitis. Both these co-morbidities could over estimate the effectiveness of treatment and possibly did so in the Herne 1980 trial. The fact that the overall pooling showed no effect means that these trials did not affect the outcome.
Effects of interventions
All analyses used the fixed-effect model unless otherwise stated.
Lack of cure and persisting symptoms
Studies reported different outcome measures but all those with analysable data reported some general aspect of improvement. This was defined as:
persistence of clinical symptoms and signs at day five ( Herne 1980 );
no benefit in 24 hours ( Hoaglund 1950 );
symptoms persistent or worse at five days ( Kaiser 1996 );
not better at day seven ( Lexomboon 1971 );
no cure or not improved in three days ( McKerrow 1961 );
not returning to normal activity ( Taylor 1977 ); and
persistence of purulent nasal discharge at day 10 ( De Sutter 2002 ).
The risk ratio (RR) of no cure or persistence was 0.95 (95% confidence interval (CI) 0.59 to 1.51, random-effects) ( Analysis 1.1 ). When we analysed results for children and adults separately, there was no significant finding for lack of cure or persistence of symptoms in either group ( Analysis 1.3 ; Analysis 1.4 ). Herne 1980 was the only study to show a benefit with antibiotics. Seven participants were removed from the analysis by the investigators because of tonsillitis and the review authors were concerned that there may have been more in this study. When Herne 1980 was removed from the analysis, the RR of no cure or persistence increased to 1.11 (95% CI 0.70 to 1.76) ( Analysis 1.2 ).
Howie 1970 reported outcomes using episodes of illness as the denominator, which meant that the data could not be pooled with the other studies. This study analysed antibiotic versus placebo by signs and symptoms (cough, purulent nasal discharge, spit and purulent spit) and found no significant differences.
Analysis by type of antibiotic was not undertaken for any of the outcomes. The results for different types of antibiotics were added together in situations where more than one antibiotic was used in a study.
The only study not to contribute to this lack of cure and persistence of symptoms analysis (other than Howie) was Gordon 1974 . Their results were expressed as P values rather than a count of participants with symptoms and they found that placebo was better at relief of symptoms than ampicillin (P = 0.05); there was no significant difference between placebo and erythromycin or placebo and penicillin. Only two participants grew beta haemolytic streptococcus in that study so it was decided to leave the study in this review.
Sensitivity analysis of lack of cure and persisting symptoms
Delay starting antibiotic and low dose antibiotic
Hoaglund 1950 assessed the outcome of treatment at 24 hours after medication was started, that is sooner than antibiotics are thought to work. McKerrow 1961 used 15 mg tablets three times daily for the three tetracycline groups in their study. Today this dose would be regarded as sub-therapeutic. Analysis excluding these two studies did not significantly change the RR ( Analysis 1.5 ).
Positive throat swabs
Kaiser 1996 found a significant benefit (cure) for antibiotics only in the subset of participants who had positive nasopharyngeal aspirates for any one of three respiratory pathogens (H. influenzae,M. catarrhalis and S. pneumoniae), which occurred in 20% of the study participants. Open treatment was prescribed for 11 (39%) participants on placebo and three (10%) participants assigned to amoxicillin/clavulanic acid. When Kaiser 1996 was excluded from the analysis there was no significant change in the effect (RR 1.00 95% CI 0.45 to 2.22) ( Analysis 1.6 ). We acknowledge the contradiction of including a study with some participants who had a bacterial diagnosis on retropharyngeal swabs while excluding studies with participants who had positive throat swabs for streptococcus.
Active medication in the control group
In Ackerman 1968 , penicillin and tetracycline were compared with a control group taking dextromethorphan (Robitussin), which is a cough suppressant and for which there was some evidence that it was effective. It thus cannot be assumed to be an inert placebo. A sensitivity analysis adding Ackerman 1968 to the other studies made no significant difference to the RR. Also, our review was directed at antibiotics versus placebo. Consequently this paper has been left out of the final analysis.
Smoking
Six of the 10 reviewed studies were in adults but smoking was considered in only one of these studies ( Howie 1970 ). In this study there was no significant difference between active and placebo treatments in terms of benefit to smokers or non smokers (P value > 0.05).
Other outcomes
Sore throat
Only two studies reported on sore throat persisting at day seven as an outcome ( Herne 1980 ; Taylor 1977 ). The RR was 0.47 95% CI 0.12 to 1.82 for persisting sore throat, with no significant difference between the treatment groups ( Analysis 4.1 ).
Loss of appetite
There was only one study which reported the lack of return of appetite at day eight ( Taylor 1977 ). The RR of a lack of return of appetite was 0.97, 95% CI 0.44 to 2.12 ( Analysis 6.1 ). Return of appetite was not specified a priori as an item warranting analysis.
Loss of time at work
The only study to report loss of time at work was Howie 1970 , where the RR for any work loss per episode of illness was 0.88, 95% CI 0.69 to 1.13 ( Analysis 5.1 ).
Sneezing
None of the studies reported sneezing as an outcome.
Adverse effects
Six studies reported adverse effects experienced by individual participants. When all studies were combined there was a significant difference for adverse effects (RR 1.80, 95% CI 1.01 to 3.21; random-effects model) but there was a high level of heterogeneity ( Analysis 1.7 ). This appeared to be due to a difference between adults and children because when analysed separately there was a significant difference for adults (RR 2.62, 95% CI 1.32 to 5.18; random-effects model) ( Analysis 1.8 ) but not for children (RR 0.91, 95% CI 0.51 to 1.63) Analysis 1.9 ; heterogeneity for the child analysis was not significant. McKerrow 1961 did not distinguish between the pneumoconiosis group and the office (unit) group so the proportion of adverse effects in the office unit group were allocated in proportion to the number of participants in the two parts of the study; with this study removed the increase in adverse effects with antibiotics was not significant (RR1.68, 95% CI 0.67 to 4.20) ( Analysis 1.10 ). Some studies did not report adverse effects ( Gordon 1974 ; Herne 1980 ; Hoaglund 1950 ; Lexomboon 1971 ; Vogt 1966 ). In the purulent rhinitis studies there was a statistically significant increase in adverse effects (RR 1.46, 95% CI 1.1 to 1.94) ( Analysis 3.4 ).
Rhinitis purulent and clear
The study by Herne 1980 did not specify if the rhinitis was purulent or not. When this study was excluded, pooling the other four antibiotic versus placebo studies for purulent rhinitis gave a RR of 0.73 (95% CI 0.47 to 1.13; random-effects model) ( Analysis 3.1 ). When Herne 1980 was added to the purulent group, the RR was 0.67 (95% CI 0.43 to 1.04; random-effects model) for persisting purulent rhinitis ( Analysis 3.2 ). Because xibornol and inhaled nitrofurazone are no longer available, pooling the three studies plus the tetracycline arm of the Herne study gave a RR of 0.74 (95% CI 0.46 to 1.18; random-effects model) for persisting purulent rhinitis on currently available antibiotics ( Analysis 3.3 ). It is worth noting that in Howie 1970 there was no significant benefit from antibiotics in participants with purulent nasal discharge but this study used illnesses, not individuals, as the denominator. Antibiotics also appeared to be not effective for clear rhinitis when Herne was added as clear rhinitis (RR 0.58, 95% CI 0.23 to 1.48; random-effects model) ( Analysis 2.1 ). Five studies reported purulent rhinitis with no additional explanation ( Howie 1970 ; Kaiser 1996 ; Taylor 1977 ; Todd 1984 ; Vogt 1966 ). De Sutter 2002 defined purulent rhinitis on a purely clinical basis (that is, the recruiting doctors made the decision). Nineteen per cent of those in Kaiser 1996 had radiologically confirmed sinusitis. Fifty-three per cent to 56% of participants in De Sutter 2002 reported unilateral facial pain. The incidence of unilateral facial pain was not reported in six trials ( Herne 1980 ; Howie 1970 ; Kaiser 1996 ; Taylor 1977 ; Todd 1984 ; Vogt 1966 ).
Discussion
Discussion
While the International Classification of Health Problems in Primary Care (ICHPPC) gives one definition of upper respiratory tract infection (URTI), it is not clear how rigidly this definition applies in practice. The review authors have accepted that the diagnosis of URTI is made on clinical grounds and treatment decisions are made on the basis of that clinical decision. Although the range of inclusion criteria appears wide, the review authors accept that the majority of participants in each study in this review were suffering from viral URTIs. Only three studies reported their findings in terms of the lower respiratory tract. Gordon 1974 reported 13% of children under two years old and 13% of those over six years to have lower respiratory tract signs. Forty-three per cent (84 out of 197) of participants in Taylor 1977 had auscultatory evidence of a more extensive peripheral airways disease.
Herne 1980 included seven participants with bronchitis: four in the tetracycline group, two in the xibornol group and one in the placebo group. In the context we assumed this diagnosis was mainly due to bronchospasm. We excluded studies with significant numbers of participants with streptococci on throat swabs (see Characteristics of excluded studies table). We included Gordon 1974 , which found 2% of participants (2 of 89) with cultures of beta haemolytic streptococci. Seven participants were excluded from Herne 1980 because the pharynx looked as though the participants had clinical streptococcal tonsillitis.
Other studies did not test for throat bacteria. Cultures that are positive for streptococci may include contaminants as well as cases of true infection. The issue of bacterial involvement is a concern for reviews of bronchitis, sore throats and upper respiratory tract infections. There is no overlap with Fahey's bronchitis review ( Fahey 1998 ) but there are two studies ( Howie 1970 ; Kaiser 1996 ) that are also in the Smith 2011 bronchitis review.
The review by Del Mar 1992 on managing sore throat included one study that is in our review ( Taylor 1977 ). Clearly the larger the proportion of illnesses caused by bacteria that exist among the cases of viral illness the more likely the findings are to show a benefit for antibiotics. There is no other way of defining the disease of interest other than perhaps doing nasopharyngeal aspirations, as done in Kaiser 1996 , and throat cultures on all participants. This is not current clinical practice and the purpose of our review is to be relevant to clinical practice.
The a priori outcomes for analysis included persistence of symptoms of nasopharyngeal inflammation, global rating of health and adverse effects. The summary risk ratio (RR) for general improvement or cure was 0.95 (95% CI 0.59 to 1.51) ( Analysis 1.1 ). In contrast with the Cochrane Review by Smith 2011 , there was no over-reporting of significant findings. Indeed, there was a tendency to under-report findings and, hence, less likelihood of a type one statistical error.
Most studies did not report adverse effects. However, the summary RR for adverse effects from the four studies in adults that had analysable data was significant. The majority of adverse effects were gastrointestinal, which is consistent with clinical anecdote. In the two studies in children there was no significant adverse effect from antibiotics, which is consistent with the findings of Fahey 1998 .
The symptoms of nasopharyngeal inflammation chosen for analysis were sore throat and runny nose, either purulent or clear. No studies reported sneezing as an outcome. Six trials provided outcome data on nasopharyngeal inflammation ( De Sutter 2002 ; Herne 1980 ; Howie 1970 ; Todd 1984 ; Taylor 1977 ; Vogt 1966 ). Data from Howie 1970 were not in a form that could be used in this review but indicated no benefit from antibiotics for purulent nasal discharge. Pooling the purulent rhinitis data suggested that antibiotics are not beneficial for this condition. For runny nose with a clear discharge there was no significant benefit when Herne 1980 and Taylor 1977 were pooled. As noted above, the definition of the type of rhinitis in Herne 1980 was not given and hence it was added to both clear and purulent rhinitis. There is collateral information about this in the literature. In an acute bronchitis study ( Stott 1976 ) there was a lower incidence of runny nose at day seven in the doxycycline group than in the placebo group (P < 0.01). There is a Cochrane Review on persisting rhinosinusitis (more than 10 days duration) which shows a benefit from treating with antibiotics ( Morris 2007 ).
Sore throats
The finding of no benefit from antibiotics for sore throat was expected. We would suggest the reader read the Cochrane Review on antibiotics for sore throat ( Spinks 2011 ). The role of bacteria in upper respiratory tract infections, either as a causal factor or a complication, is highlighted in Kaiser 1996 . The authors make a convincing argument for the role of three types of bacteria (H. influenzae, M. catarrhalis and S. pneumoniae). It would be helpful to see this work repeated in another centre. Treatment in this subgroup resulted in one day less of symptoms.
Sinusitis or purulent rhinitis
The difference between sinusitis and acute purulent rhinitis is not clear. There is presumably an overlap: 19% of the participants in Kaiser 1996 had radiological sinusitis and between 53% and 56% of the participants in De Sutter 2002 had unilateral facial pain. In one study, which was excluded because of a greater than 10-day duration of purulent rhinitis, all participants had to have facial X-rays free of abnormalities ( Haye 1998 ). In this study azithromycin was significantly more effective than placebo on the outcome of purulent rhinitis. This suggests that participants may be able to have purulent rhinitis without sinus involvement. These issues need to be taken into account in future studies. The methodological quality of the studies before 1990 was low and hence it is difficult to draw firm conclusions from these.
Generalisability
Although only three of the studies were conducted in general practice ( De Sutter 2002 ; Howie 1970 ; Taylor 1977 ), the others seemed to represent a cross-section of participants seen in primary care settings. This indicates that our results are generalisable to the wider primary care setting if the assumption is made that participants can self refer to these secondary care settings and use them as primary care providers. Other study settings were:
a military base ( Hoaglund 1950 ); unit staff ( McKerrow 1961 );
hospital outpatients ( Kaiser 1996 ; Lexomboon 1971 );
paediatricians in private practice ( Vogt 1966 );
casualty clinic ( Gordon 1974 ); and
military base ( Herne 1980 ; Todd 1984 ).
The heterogeneity of the pooled data for adverse effects from all the studies appears to come from the difference between adverse effects in adults and children. There was no heterogeneity when they were analysed separately. In one arm of Taylor 1977 the group taking co-trimoxazole had more adverse effects than the placebo group, while the amoxycillin group had fewer. None of the children were given amoxycillin/clavulanic acid, which contributed a lot to the adverse effects in Kaiser 1996 . This finding in children is consistent with Fahey 1998 . That review included the two studies in our review and three which we excluded. This negative finding in children relates mainly to the unexpected findings in Taylor 1977 . There is no methodological reason for this and our assumption would be that this is a chance (and erroneous) finding. The expected finding would be for children to get more adverse effects in the antibiotic group, as was found in the Cochrane Review on antibiotics for acute otitis media ( Venekamp 2013 ). The adverse effects in the purulent rhinitis group were statistically significant.
Summary of main results
The RR for lack of cure or persistence of symptoms is 0.95, 95% CI 0.59 to 1.51 ( Analysis 1.1 ). The overall RR for adverse effects for antibiotics given to participants with the common cold is 1.8, 95% CI 1.01 to 3.21 ( Analysis 1.7 ) and for purulent rhinitis is 1.46, 95% CI 1.1 to 1.94 ( Analysis 3.4 ). The overall RR for the antibiotic treatment of persisting acute purulent rhinitis is 0.73, 95% CI 0.47 to 1.13 ( Analysis 3.1 ). In summary, there is no benefit for antibiotics for the common cold or acute purulent rhinitis but there is an increase in adverse effects.
Overall completeness and applicability of evidence
There is unclear risk of bias across the studies. All of the trials were randomised controlled trials (RCTs). However, methods of randomisation were not always clear. All the medications were identical in each trial. Most of the participants had a viral upper respiratory tract infection but some may have had bacterial chest or sinus infections.
Quality of the evidence
See comments in previous section.
Potential biases in the review process
The major bias is likely to be the inclusion of participants with bacterial disease such as streptococcal tonsillitis or bacterial sinusitis. The fact that the pooled result was not significant may mean this is a small consideration.
Agreements and disagreements with other studies or reviews
The findings of this study are consistent with two reviews in children, Gadomski 1993 and Fahey 1998 , which found no benefit for antibiotics.
Authors' conclusions
Implications for practice
Antibiotics offer no benefit in the initial treatment of the common cold (acute upper respiratory tract infections (URTIs)). Antibiotics should not be given in the first instance as they will not improve the symptoms and adult participants will be affected by their adverse effects. Antibiotics offer no benefit for acute purulent rhinitis while there is an increase in adverse effects. However, if the symptoms persist for more than 10 days then antibiotic therapy may be beneficial ( Morris 2007 ) and clinicians may wish to negotiate the use of them with patients, taking into account the resistance issues.
Implications for research
Further research is needed on the role of pathogenic nasopharyngeal bacteria and their presence in URTIs. Studies need to be more diligent in reporting adverse effects and symptoms.
Acknowledgements
Acknowledgements
The Charitable Trust of the Auckland Faculty of the Royal New Zealand College of General Practice (RNZCGP) for a grant to undertake the literature search. Thanks to Elspeth Kay for editing the penultimate version in Arroll 2005 . The authors also wish to thank Leonard Leibovici, Mark Jones, Janet Yarrow and Dennis Conrad for commenting on the draft Arroll 2005 review.
Notes
References
References to studies included in this review
De Sutter 2002 {published data only}
Sutter AI, Meyere MJ, Christiaens TC, Duriel ML, Peersman W, Maeseneer JM. Does amoxicillin improve outcomes in patients with purulent rhinorrhea?. Journal of Family Practice 2002;51:317-23.
Gordon 1974 {published data only}
Gordon M, Lovell S, Dugdale AE. The value of antibiotics in minor respiratory illness in children. Medical Journal of Australia 1974;1:304-6.
Herne 1980 {published data only}
Herne N. Double blinded randomized trial comparing xibornol, tetracycline and placebo in seasonal upper respiratory tract infections. Medicines et Maladies Infectieuses 1980;10:185-90.
Hoaglund 1950 {published data only}
Hoaglund RJ, Dietz EN, Myers PW, Cosand HC. Aureomycin in the treatment of the common cold. New England Journal of Medicine 1950;243:773-5.
Howie 1970 {published data only}
Howie JG, Clark GA. Double-blind trial of early demethylchlortetracycline in minor respiratory illness in general practice. Lancet 1970;2:1099-102.
Kaiser 1996 {published data only}
Kaiser L, Lew D, Hirshel B, Auckenthaler R, Morabia A, Heald A. Effects of antibiotic treatment in the subset of common-cold patients who have bacteria in nasopharyngeal secretions. Lancet 1996;1996:1507-10.
Lexomboon 1971 {published data only}
Lexomboon U, Duangmani C, Kusalasai V, Sunakorn P, Olson LC, Noyes HE. Evaluation of orally administered antibiotics for treatment of upper respiratory infections in Thai children. Journal of Pediatrics 1971;78:772-8.
McKerrow 1961 {published data only}
McKerrow CB, Oldham PD, Thomson S. Antibiotics and the common cold. Lancet 1961;1:185-7.
Taylor 1977 {published data only}
Taylor B, Abbott GD, Kerr MM. Amoxycillin and co-trimoxazole in presumed viral respiratory infections in childhood: a placebo controlled trial. BMJ 1977;2:552-4.
Todd 1984 {published data only}
Todd JK, Todd N, Damanto J, Todd WA. Bacteriology and treatment of purulent nasopharyngitis: a double blind, placebo-controlled evaluation. Pediatric Infectious Diseases 1984;3:226-32.
Vogt 1966 {published data only}
Vogt FC. Medical management of purulent rhinitis. A double-blind comparison of vasoconstrictor agent alone with a combination of vasoconstrictor and antimicrobial drugs. Clinical Pediatrics 1966;5:547-9.
* indicates the major publication for the study
References to studies excluded from this review
Ackerman 1968 {published data only}
Ackerman BD. Treatment of undifferentiated respiratory infections in infants. Clinical Pediatrics 1968;7:391-5.
Banks 1965 {published data only}
Banks HS. Common cold: controlled clinical trials. British Medical Journal 1965;2:650-.
Banks 1969 {published data only}
Banks HS, Ritchies JM. Re-appraisal: a new look at the common cold. Journal of the Royal College of General Practitioners 1969;18:166-72.
Bateson 1961 {published data only}
Bateson PR, Allison RM, Wall T, Sons . The treatment of the common cold with antibiotics in a factory population. British Journal of Clinical Practice 1961;15:543-9.
Bessel-Lorck 1959 {published data only}
Bessel-Lorck . Prophylaxis for common cold in adolescents in a skiing camp. Die Medizinische Welt 1959;10:2126-7.
Burke 1956 {published data only}
Burke JB. Prophylactic sulphadimidine in children subject to recurrent infections of upper respiratory tract. British Medical Journal 1956;March 10:538-41.
Cronk 1954 {published data only}
Cronk GO, Naumann DE, McDermott K. A controlled study of oral penicillin G in the treatment of non-specific upper respiratory infections. American Journal of Medicine 1954;16:804-9.
Darelid 1993 {published data only}
Darelid J, Lofgren S, Malmvall BE. Erythromycin treatment is beneficial for longstanding Moraxella catarrhalis associated cough in children. Scandinavian Journal of Infectious Diseases 1993;25:323-9.
Fraser 1962 {published data only}
Fraser PK, Hatch LA, Hughes KEA. A comparison between aspirin and antibiotics in the treatment of minor respiratory infections. Lancet 1962;1:614-7.
Gottfarb 1994 {published data only}
Gottfarb P, Bruaner A. Children with persistent cough-outcome with treatment and role of Moraxella catarrhalis. Scandinavian Journal of Infectious Diseases 1994;26:545-51.
Gupta 1997 {published data only}
Gupta S, Bhushan V, Srivastava G. The therapeutic trial of chloramphenicol, Eskaycillin (ampicillin) and co-trimoxazole in respiratory tract infection of childhood. Indian Paediatrics 1977;14:391-3.
Haight 1954 {published data only}
Haight TH, Kahn FH, Ziegra SR. Efficacy of erythromycin in the treatment of acute respiratory infections. US Armed Forces Medical Journal 1954;5:1405-22.
Hardy 1956 {published data only}
Hardy LM, Traismam HS. Antibiotics and chemotherapeutic agents in the treatment of uncomplicated respiratory infections in children. Journal of Pediatrics 1956;48:146-56.
Haye 1998 {published data only}
Haye R, Lingaas E, Hoivik HO, Odegard T. Azithromycin versus placebo in acute infectious rhinitis with clinical symptoms but without radiological signs of maxillary sinusitis. European Journal of Clinical Microbiology and Infectious Diseases 1998;17:309-12.
Jones 1953 {published data only}
Jones PN, Bigham RS, Manning PR. Use of antibiotics in nonbacterial respiratory infections. Journal of the American Medical Association 1953;153:262-4.
Knox 1962 {published data only}
Knox JDE. Comparison between aspirin and anti-biotics in minor respiratory infections. Lancet 1962;1:1358-9.
Kuh 1949 {published data only}
Kuh C, Collen MF. Mass penicillin prophylaxis: an experiment with negative results. Journal of the American Medical Association 1949;140:1324-8.
Lapin 1984 {published data only}
Lapin JH. Prophylaxis of upper respiratory infections in children treated with oral penicillin. Journal of Pediatrics 1948;32:119-24.
Lockhart 1961 {published data only}
Lockhart R. Treatment of common cold by Terramycin. Health Bulletin 1961;19:12-3.
Marlow 1989 {published data only}
Marlow RA, Torrez AJ, Haxby D. The treatment of non-streptococcal pharyngitis with erythromycin. A preliminary study. Family Medicine 1989;21:425-7.
McLane 1952 {published data only}
McLane RA. Clinical evaluation of combined drug therapy in acute upper respiratory infections. Journal of the Medical Society of New Jersey 1952;49:509-10.
Reinert 1991 {published data only}
Reinert P, Narcy P, Paliwoda A, Rouffiac E. Evaluation of tisocortal pivalate-neomycin combination versus a placebo excipient in acute rhinopharyngitis in children. Annals de Pediatrie 1991;38:503-8.
Ritchie 1958 {published data only}
Ritchie JM. Antibiotics in small doses for the common cold. Lancet 1958;1:618-21.
Seal 1953 {published data only}
Seal JR. The prophylaxis of acute respiratory infections with oral penicillin or chlortetracycline - proceedings of the symposium on antibiotics. Antibiotics Annual. Medical Encyclopedia Inc, 1953-4.
Sulman 1958 {published data only}
Sulman FG. Chloramphenicol and control of the common cold. Lancet 1958;ii:1355-6.
Sutrisna 1991 {published data only}
Sutrisna B, Freruchs RR, Reingold AL. Randomised controlled trial of effectiveness of ampicillin in mild acute respiratory infections in Indonesian children. Lancet 1991;338:471-4.
Townsend 1960 {published data only}
Townsend EH. Chemoprophylaxis during respiratory infections in private pediatric practice. American Journal of Diseases in Children 1960;99:566-73.
Townsend 1962 {published data only}
Townsend EH, Radebaugh JF. Prevention of complications of respiratory illness in pediatric practice. New England Journal of Medicine 1962;266:683-9.
Traisman 1955 {published data only}
Traisman HS. A controlled study in the uses of chemotherapeutic and antibiotic agents in uncomplicated upper respiratory infections in children. Illinois Medical Journal 1955;107:221-4.
Wald 1991 {published data only}
Wald ER. Purulent nasal discharge. Pediatric Infectious Diseases Journal 1991;10:329-33.
Walker 1955 {published data only}
Walker SH. Tetracycline in the control of upper respiratory infections of infants. In: Antibiotics Annual New York: Medical Encyclopedia, Inc:341-4.
Wynn-Williams 1961 {published data only}
Wynn-Williams SH. Tetracycline in the control of common upper respiratory infections of infants. In: Antibiotic Annual New York: Medical Encyclopedia, Inc, 1961:341-4.
Additional references
Arason 1996
Arason A, Kristinsson KG, Sigurdsson JA, Stefansdottir G, Molstad S, Gudmundsson S. Do antimicrobials increase the carriage rate of penicillin resistant pneumococci in children? Cross sectional prevalence study. BMJ 1996;313:387-91.
Arroll 2000
Arroll B, Goodyear-Smith F. General practitioner management of upper respiratory tract infections: when are antibiotics prescribed?. New Zealand Medical Journal 2000;113:493-6.
Arroll 2001
Arroll B, Kenealy T. Antibiotics for acute bronchitis. Four reviews and still no answers: our clinical definitions are at fault. BMJ 2001;322:939-40.
Del Mar 1992
Mar C. Managing sore throat: a literature review, II. Do antibiotics confer benefit?. Medical Journal of Australia 1992;156:644-9.
Fahey 1998
Fahey T, Stocks N, Thomas T. Quantitative systematic review of randomised controlled trials comparing antibiotic with placebo for acute cough in adults. BMJ 1998;316:906-10.
Gadomski 1993
Gadomski AM. Potential interventions for preventing pneumonia among young children: lack of effect of antibiotic treatment for upper respiratory infections. Pediatric Infectious Disease Journal 1993;12:115-20.
Gonzales 1999
Gonzales R, Barrett P, Steiner J. The relation between purulent manifestations and antibiotic treatment of upper respiratory tract infections. Journal of General Internal Medicine 1999;14:151-6.
Higgins 2011
Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration. 2011:-.
ICHPPC 1986
ICHPPC-2 . In: International Classification of Health Problems in Primary Care Oxford: Oxford University Press, 1986:-.
Kaplan 1971
Kaplan EL, Top FH, Dudding BA, Wannamake L. Diagnosis of streptococcal pharyngitis: differentiation of active infection from the carrier state in the symptomatic child. Journal of Infectious Diseases 1971;123:490-501.
Lefebvre 2011
Lefebvre C, Manheimer E, Glanville J. Chapter 6: Searching for studies. In: Higgins JPT, Green S, editor(s). Cochrane Handbook for Systematic Reviews of Interventions. Version 5.1.0 [updated March 2011]. The Cochrane Collaboration. Available from www.cochrane-handbook.org Chichester: Wiley-Blackwell, 2011:-.
Mainous 1997
Mainous AG, Hueston WJ, Eberlain C. Colour of respiratory discharge and antibiotic use. Lancet 1997;350:1077-.
McAvoy 1994
McAvoy B, Davis P, Raymont A, Gribben B. The Waikato Medical Care Survey. New Zealand Medical Journal 1994;107:387-433.
McGregor 1995
McGregor A, Dovey S, Tilyard M. Antibiotic use in upper respiratory tract infections in New Zealand. Family Practice 1995;12:166-70.
Morris 2007
Morris PS, Leach AJ. Antibiotics for persistent nasal discharge (rhinosinusitis) in children. Cochrane Database of Systematic Reviews 2007:-.
Ochoa 2000
Ochoa C, Eiros JM, Inglada L, Vallano A, Guerra L. Assessment of antibiotic prescription in acute respiratory infections in adults. The Spanish study group on antibiotic treatment. Journal of Infection 2000;41:73-80.
Pharmac 2008
Pharmac . Annual review. 2008:16-.
RevMan 2012
Review Manager (RevMan). 2012:-.
Reynolds 1996
Reynolds JEF, Parfitt K (editors). In: Martindale: The Extra Pharmacopeia London: Royal Pharmaceutical Society, 1996:-.
Rosenstein 1998
Rosenstein N, Phillips W, Gerber M, Marcy S, Schwartz B, Dowell S. The common cold - principles of judicious use of antimicrobial agents. Pediatrics 1998;101:181-4.
Smith 2011
Smith S, Fahey T, Smucny J, Becker L. Antibiotics for acute bronchitis. Cochrane Database of Systematic Reviews 2011:-.
Snow 2001
Snow V, Mottur-Pilson C, Gonzales R. Principles of appropriate antibiotic use for treatment of non specific upper respiratory tract infections in adults. Annals of Internal Medicine 2001;134:487-9.
Spector 1995
Spector SL. The common cold: current therapy and natural history. Journal of Allergy and Clinical Immunology 1995;95:1133-8.
Spinks 2011
Spinks A, Glasziou PP, Mar C. Antibiotics for sore throat. Cochrane Database of Systematic Reviews 2011:-.
Stott 1976
Stott NC, West RR. Randomised controlled trial of antibiotics in patients with cough and purulent sputum. British Medical Journal 1976;2:556-9.
Venekamp 2013
Venekamp RP, Sanders S, Glasziou PP, Mar CB, Rovers MM. Antibiotics for acute otitis media in children. Cochrane Database of Systematic Reviews 2013:-.
Verkatesum 1995
Verkatesum P, Innes JA. Antibiotic resistance in common acute respiratory pathogens. Thorax 1995;50:481-3.
Graphs
Graphs and Tables
To view a graph or table, click on the outcome title of the summary table below.
| Outcome title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Persisting symptoms 1 to 7 days | 6 | 1047 | Risk Ratio (M-H, Random, 95% CI) | 0.95 [0.59, 1.51] |
| 2 Persisting symptoms day 1 to 7 with Herne out | 5 | 979 | Risk Ratio (M-H, Random, 95% CI) | 1.11 [0.70, 1.76] |
| 3 Persisting symptoms days 1 to 7 in adults | 4 | 891 | Risk Ratio (M-H, Fixed, 95% CI) | 0.92 [0.78, 1.07] |
| 4 Persisting symptoms day 1 to 7 children only | 2 | 449 | Risk Ratio (M-H, Fixed, 95% CI) | 1.36 [0.59, 3.15] |
| 5 Persisting symptoms day 1 to 7 with Hoagland and McKerrow out | 3 | 810 | Risk Ratio (M-H, Fixed, 95% CI) | 1.00 [0.85, 1.19] |
| 6 Persisting symptoms 1 to 7 days with Kaiser out | 5 | 759 | Risk Ratio (M-H, Random, 95% CI) | 1.00 [0.45, 2.22] |
| 7 Adverse effects | 6 | 1495 | Risk Ratio (M-H, Random, 95% CI) | 1.80 [1.01, 3.21] |
| 8 Adverse effects in adults | 4 | 1267 | Risk Ratio (M-H, Random, 95% CI) | 2.62 [1.32, 5.18] |
| 9 Adverse effects in children | 2 | 228 | Risk Ratio (M-H, Fixed, 95% CI) | 0.91 [0.51, 1.63] |
| 10 Adverse effects with McKerrow out | 4 | 1054 | Risk Ratio (M-H, Random, 95% CI) | 1.68 [0.67, 4.20] |
| Outcome title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Persistent rhinitis (purulent) | 4 | 723 | Risk Ratio (M-H, Random, 95% CI) | 0.73 [0.47, 1.13] |
| 2 Persistent purulent rhinitis with Herne added as purulent | 5 | 791 | Risk Ratio (M-H, Random, 95% CI) | 0.67 [0.43, 1.04] |
| 3 Persistent purulent rhinitis with currently available medication | 4 | 658 | Risk Ratio (M-H, Random, 95% CI) | 0.74 [0.46, 1.18] |
| 4 Adverse effects for purulent rhinitis studies | 4 | 1174 | Risk Ratio (M-H, Fixed, 95% CI) | 1.46 [1.10, 1.94] |
| Outcome title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Sore throat at day 7 | 2 | 234 | Risk Ratio (M-H, Random, 95% CI) | 0.47 [0.12, 1.82] |
| Outcome title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Any work loss | 1 | 836 | Risk Ratio (M-H, Fixed, 95% CI) | 0.88 [0.69, 1.13] |
| Outcome title | No. of studies | No. of participants | Statistical method | Effect size |
|---|---|---|---|---|
| 1 Loss of appetite at day 8 | 1 | 188 | Risk Ratio (M-H, Fixed, 95% CI) | 0.97 [0.44, 2.12] |
Cover sheet
| Reviewer(s) | Kenealy Tim, Arroll Bruce |
| Contribution of Reviewer(s) | |
| Issue protocol first published | 1997 issue 3 |
| Issue review first published | 1998 issue 4 |
| Date of last minor amendment | Information not supplied by reviewer |
| Date of last substantive amendment | Information not supplied by reviewer |
| Most recent changes | |
| Date new studies sought but none found | Information not supplied by reviewer |
| Date new studies found but not yet included/excluded | Information not supplied by reviewer |
| Date new studies found and included/excluded | Information not supplied by reviewer |
| Date reviewers' conclusions section amended | Information not supplied by reviewer |
| Contact address | Kenealy Private Bag 92019 Auckland New Zealand Telephone: Facsimile: E-mail: t.kenealy@cochraneprimarycare.org |
| Cochrane Library number | CD000247 |
| Editorial group | Cochrane Acute Respiratory Infections Group |
| Editorial group code | HM-ARI |
Sources of support
External sources of support
- The Charitable Trust of the Auckland Faculty of the Royal New Zealand College of General Practitioners, New Zealand.
- The National Prescribing Service of Australia (NPS), Australia.
Internal sources of support
- No sources of support supplied
Comments and criticisms
Antibiotics for the common cold
Summary of comments and criticisms
METHODS and METHODOLOGICAL QUALITIES OF INCLUDED STUDIES
The reviewers use a scoring system for methodological quality, whereby each trial is given a numerical score on a scale of 1 to 12 points, which they say is described in the Cochrane Handbook. The Handbook in fact advises against composite scores as they are not transparent. In the Methodological quality of included studies section, the reviewer's then say that they do not think that these scores are an accurate measure of study quality. Furthermore, trial quality is not incorporated into interpretation of the results. It is therefore difficult for the reader to assess how systematic bias in the included studies might have affected the findings reported in the review.
The reviewers use a scoring system for methodological quality, whereby each trial is given a numerical score on a scale of 1 to 12 points, which they say is described in the Cochrane Handbook. The Handbook in fact advises against composite scores as they are not transparent. In the Methodological quality of included studies section, the reviewer's then say that they do not think that these scores are an accurate measure of study quality. Furthermore, trial quality is not incorporated into interpretation of the results. It is therefore difficult for the reader to assess how systematic bias in the included studies might have affected the findings reported in the review.
It is not clear how concealment of allocation in each trial was assessed. Have the reviewers erroneously used reporting of double blinding in the trials to assess concealment of the allocation sequence? The trials Howie 1970, Kaiser 1996 and Taylor 1977 are reported as having adequate concealment of allocation (A) yet there is no description of how this was achieved. In the trials Hoaglund 1950 and Lexomboom 1971, allocation concealment is reported as unclear (B) yet, according to the Table of characteristics of included studies, in the latter only the pharmacist knew of allocation. Also, why have the reviewers use the option (D) not to assign a score for allocation concealment to the trial Sutrisna 1991? The reader can not find any information in the review about adequacy of allocation concealment for the trial Gordon 1974.
The statement, in Methodological quality of included studies, that "Loss to follow-up was an issue for a number of studies..." needs to be expanded and loss to follow-up in each trial should be documented in the table of characteristics of included studies. Presumably the denominators used in the analyses are participants who were evaluable? How might loss to follow-up have affected the findings in the review (worst case and best case scenario)?
RESULTS
In the meta-analysis of General improvement, it would be better to present the Hoaglund study separately if, as the reviewer's say, there is good biological reason why measuring this outcome at 24 hours does not make sense.
In the meta-analysis of General improvement, it would be better to present the Hoaglund study separately if, as the reviewer's say, there is good biological reason why measuring this outcome at 24 hours does not make sense.
It is questionable to calculate numbers needed to treat and numbers needed to harm from pooled data without qualification of the conditions to which they apply, and they should not be reported without confidence intervals.
There are several inconsistencies in the numerical data reported in the text compared with the graphs.
CONCLUSIONS
The statement, in Implications for practice, that "many participants will get adverse effects" from antibiotics is not supported by evidence presented in the review. The principle of using a random effect model of analysis where there is significant heterogeneity, without going on to explore possible reasons to explain it, is questionable.
The statement, in Implications for practice, that "many participants will get adverse effects" from antibiotics is not supported by evidence presented in the review. The principle of using a random effect model of analysis where there is significant heterogeneity, without going on to explore possible reasons to explain it, is questionable.
REFERENCES
The references should be listed in the appropriate reference sections rather than included as text at the end of the conclusions.
The references should be listed in the appropriate reference sections rather than included as text at the end of the conclusions.
The above comment was made as part of a collaborative effort coordinated by Ole Olsen at the Nordic Cochrane Centre. All new reviews on Cochrane Library 1998.4 were selected and critically read by a set of methodologists, comments were coordinated and finally fed back. The general results of the survey will be presented at the Cochrane Colloquium in Rome, October 1999.
I certify that I have no affiliations with or involvement in any organisation or entity with a direct financial interest in the subject matter of my criticisms.
Reviewer's reply
Contributors to comment
Heather McIntosh
Keywords
Adult; Child; Humans; Acute Disease ; Anti-Bacterial Agents [*therapeutic use] ; Common Cold [*drug therapy] ; Randomized Controlled Trials as Topic ; Rhinitis [*drug therapy] ; Suppuration [drug therapy] ; Treatment Failure
History
History
Protocol first published: Issue 3, 1997
Review first published: Issue 4, 1998
Review first published: Issue 4, 1998
| Date | Event | Description |
|---|---|---|
| 11 August 2009 | Amended | Searches conducted. No new studies were found. We have made a few amendments, for example, changing Herne 1980 to one antibiotic group and Taylor 1977 to one antibiotic group. This has the impact of reducing the weight for these studies in the random-effects analysis, hence this is a conservative bias but our conclusions remain unchanged. Antibiotics are not effective as an initial treatment for patients with the common cold. Our analysis now shows no benefit for antibiotics for acute purulent rhinitis and our recommendation is that they should not be used initially. It may be reasonable to negotiate the use of antibiotics with patients if the purulent rhinitis persists for more than 10 days. However, even in these cases, most patients get better without antibiotics. |
| 18 July 2008 | Amended | Converted to new review format. |
| 8 March 2005 | New search has been performed | In this updated review (2005) an additional four studies were identified and added to the review. The first, Herne 1980 , was in French, which necessitated translation into English. The addition of this result has not altered the findings of the common cold systematic review. The other papers added to the review were the studies by De Sutter 2002 , Todd 1984 and Vogt 1966 , which dealt with the treatment of purulent rhinitis. It was pointed out to us by peer reviewers that two studies, Howie 1970 and Kaiser 1996 , included patients with purulent rhinitis and hence we decided to expand the review to include patients with acute purulent rhinitis. While there is some variation in the findings, they are suggestive of there being a benefit from antibiotics for this condition. In the past, guidelines have suggested not using antibiotics as they are not effective. The review authors suggest not recommending antibiotics in the first instance as most people will get better without them. |
| 16 November 2004 | Feedback has been incorporated | Feedback comment and reply added. |
| 31 July 2001 | New search has been performed | Searches conducted. |
| 20 July 1997 | New search has been performed | Review first published Issue 4, 1998. |
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