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Cite this article as: BMJ, doi:10.1136/bmj.38891.681215.AE (published 21 July 2006)
Are antibiotics effective for acute purulent rhinitis? Systematic
review and meta-analysis of placebo controlled randomised trials
B Arroll, T Kenealy
Concern exists about overuse of antibiotics leading to bacte- rial resistance.9 Most antibiotics are used in primary care, so this Objective To systematically review the evidence for the
is where any reduction needs to take place. As antibiotic use is effectiveness of antibiotics in acute purulent rhinitis (many often based on the presence of purulent rhinitis, determining guidelines advise against their use on the basis of one study that whether antibiotics are effective in this condition is important.
Our aim was to systematically search for studies on the effective- Data sources Medline, Embase, Cochrane Register of
ness and harms of antibiotics for acute purulent rhinitis and to Controlled Trials, and reference lists of retrieved articles.
do a meta-analysis and review of the articles.
Review methods Meta-analysis of data from double blind
randomised placebo controlled trials comparing antibiotics
with placebo for acute purulent rhinitis (duration less than 10
Results Seven studies were retrieved; four contributed data on
Inclusion and exclusion criteria—We included controlled trials in benefits of antibiotics, and four contributed data on harms of which the intervention was an antibiotic compared with a antibiotics. The pooled relative risk of benefit for persistent placebo for patients with acute purulent rhinitis. The primary purulent rhinitis at five to eight days with antibiotics was 1.18 outcomes were persistence versus clearance of purulent rhinitis (95% confidence interval 1.05 to 1.33). The numbers needed to and any adverse events reported. We defined “acute” as most treat ranged from 7 to 15 when the pooled relative risk was patients having less than 10 days with this symptom. We chose 10 applied to the range of control event rates. The relative risk for days to separate our review from the Cochrane review of chronic adverse effects with antibiotics was 1.46 (1.10 to 1.94). The purulent rhinitis, which used 10 days as the starting point for the numbers needed to harm for adverse effects ranged from 12 to inclusion criteria.10 The patients could be seen in any setting 78. No serious harms were reported in the placebo arms.
equivalent to general practice (that is, they could self refer). We Conclusions Antibiotics are probably effective for acute
did not limit the age of participants but excluded patients who purulent rhinitis. They can cause harm, usually in the form of were considered, in the original studies, to have sinusitis.
gastrointestinal effects. Most patients will get better without Searches—We searched (to 13 November 2005) Medline, antibiotics, supporting the current “no antibiotic as first line” Embase, and the Cochrane controlled trials register, using the terms “purulent and (rhinitis or nasopharyngitis or rhinorrheaor rhinorrhoea).” An alternative search on the rhinitis terms andrandomised controlled trial found no further relevant papers.
We also considered all the papers in the Cochrane review onantibiotics for the common cold and acute purulent rhinitis and Acute purulent rhinitis (a runny nose with coloured discharge) is the review on antibiotics for acute maxillary sinusitis.11 12 We con- a common feature of the common cold. One study of the natural tacted the authors of published controlled trials of antibiotics for history of acute rhinitis stated that clear and purulent rhinitis the common cold to see if they were aware of any unpublished both lasted about two weeks,1 although the duration might vary studies. We imposed no language restriction.
with the prevalence of specific infecting organisms. Nevertheless, Selection, validity assessment, and data abstraction—Each author the presence of purulent nasal discharge has repeatedly been independently assessed the titles and abstracts of potential shown to be an important determinant of the prescribing of papers; assessed the included trials for the quality of randomisa- antibiotics for respiratory tract infections for both adults and tion, concealment of allocation, co-interventions, losses to children.2–4 Indeed, one study found that purulent nasal follow-up, intention to treat analysis, degree of blinding, and discharge was a stronger predictor of antibiotic prescribing than extraction of data; and scored the trials by using the Jadad scale.13 Disagreement between the authors was readily resolved by Most guidelines recommend that antibiotics should not be used for this condition,5 6 citing one study that found no evidence that antibiotics reduce the duration of acute purulent rhinitis.7 Cochrane Centre, Rigshospitalet, 2003) to assess the pooled However, a recent larger study reported that treatment with relative risks and 95% confidence intervals.14 We present results amoxicillin reduced the duration of purulent rhinitis, although it of both random effects and fixed effects models for the main found no significant difference between the groups in terms of analysis; for simplicity, we present results of only the fixed effects BMJ Online First
Copyright 2006 BMJ Publishing Group Ltd
ics (none found).15 However, the adverse effect reports were Search on purulent and (rhinitis or nasopharyngitis or rhinorrhea or based on individual patients and so contribute to the harms analysis. Vogt found a significant improvement with antibiotic but was excluded as the antibiotic treatment was topical and Cochrane Controlled Trials Register papers (n=32) compared with a locally active agent rather than placebo, an oral antibiotic was given to “most patients” in both groups, and the Taylor (and Vogt) included only children, De Sutter included children and adults, and the other studies included only adults.
Three studies reported purulent rhinitis without further Papers included (n=7) (1 excluded, see text) explanation.7 15 16 De Sutter relied on the clinical decision of therecruiting doctors, although we noted that 53-56% of participants reported unilateral facial pain8; the other studies didnot report the incidence of unilateral facial pain.
Quantitative analyses
Search results and study characteristics
The pooled effect for the studies contributing data specifically on Figure 1 shows the search strategy, and the table summarises the purulent rhinitis shows a significant benefit from antibiotics at studies found. The searches found five papers on purulent rhini- five to eight days (fig 2)—relative risk 1.18 (95% confidence inter- tis (De Sutter 2002, Howie 1970, Taylor 1977, Todd 1984, and val 1.05 to 1.33, random effects); 1.21 (1.08 to 1.35, fixed effects).
Vogt 1966).7 8 15–17 A further paper (Herne 1980) reported a If data from Herne are included as purulent rhinitis, the relative reduction in rhinitis without stating if the rhinitis was purulent or risk is 1.21 (1.09 to 1.34, fixed effects). Using a relative risk of clear18; we therefore did analyses both including and excluding 1.18, the numbers needed to treat for a benefit from antibiotics this study. Another study reported a reduction in rhinitis, also ranged from seven for a baseline rate of 0.8516 20 to 15 for a base- without stating if this was purulent or clear, but we did not include it as the numerical data were not suitable for pooling.19 Various antibiotics were used: demethylchlortetracycline in Howie used illnesses, not individual patients, as the denominator Howie (1970), amoxicillin and co-trimoxazole in Taylor (1977), and hence is not pooled in the analysis of benefit from antibiot- cefalexin in Todd (1984), and amoxicillin in De Sutter (2002).
Studies included in quantitative analysis Participants
Jadad score
General practice patients aged 12 years or Duration of purulent rhinitis: benefit with above with respiratory tract infection and antibiotic (P=0.007). At eight days (personal purulent rhinitis. Mean age: amoxicillin 37 communication, De Sutter): no purulent rhinitis antibiotic 125/180, placebo 95/179. Adverse effects: diarrhoea with antibiotic 59/202,placebo 39/206; “no significant difference” invomiting, abdominal pain, or rash At day five: no rhinitis with antibiotic 43/46, upper respiratory tract infections with no placebo 17/22 (not stated if purulent or clear).
seemed to have streptococcal tonsillitis;therefore, n=68. No dropouts Adverse effects: antibiotic 25/293, placebo 20-49. Self administered drug to start if 7/250 (not significant). Five patients had adverse effects more than once, so antibiotic getting better after two days. No physical 20/288 (patients as denominator). No duration examination, so no lower respiratory tract given for outcome measures. All adverse effects signs reported. 829 potential participants: “gastrointestinal,” except one possible drug 293 took antibiotics, 250 took placebo, 66 excluded due to chronic respiratory signsor symptoms, 198 took no drug, 22returned no cards Children aged 2-10 years. General practice At day eight, no purulent rhinitis: amoxicillin 51/54, co-trimoxazole 72/75, placebo 50/59 pharyngotonsillitis, or bronchitis; 43% had (assigned as 25/30 to each group for analysis).
Comparing cefalexin only and placebo only at day 5-6: no purulent rhinitis, cefalexin 6/26, anterior nasal discharge due to infection.
placebo 9/24. Adverse effects (rash, diarrhoea, vomiting, hyperactivity): 2/23, placebo 4/17 mg/kg/day (maximum 2 g). Drugcode broken if group Astreptococcus found onnasopharyngeal cultures, and patientexcluded if got a treatable illnesssuch as otitis media “Excellent” or “good” clearance of purulent rhinitis at four days: antibiotic 44/50, placebo BMJ Online First
Pooling the two studies that used amoxicillin gives a relative risk than placebo in clearing purulent rhinitis. It seems that antibiot- of 1.26 (1.11 to 1.45, fixed effects).
ics may help purulent rhinitis, with or without the presence of The pooled relative risk for adverse effects was 1.46 (1.10 to sinusitis. Any future studies, however, should specifically assess 1.94, fixed effects), obtained from four studies.7 8 15 16 The numbers needed to harm ranged from 12 to 78 for control event Our findings differ from the received wisdom in terms of the rates in the statistically significant studies (0.1898 to 0.02815). The effectiveness of antibiotics for acute purulent rhinitis. This high- harms were mainly gastrointestinal and a small number of lights the dangers of relying on one study (Todd)7 to decide on the effectiveness of a treatment when other studies show a differ- A funnel plot suggests a paucity of small studies with small or ent effect. Our summation would be to suggest initial no effects. All of the included studies scored five out of five on the management by non-antibiotic treatments or “watchful waiting,” and that antibiotics should be used only when symptoms havepersisted for long enough to concern parents or patients. In this Discussion
case, antibiotic treatment may be considered, given that theharms were usually gastrointestinal adverse effects and that indi- The findings from this study indicate that antibiotics for acute vidual patients may be aware of their own ability to tolerate spe- purulent rhinitis may be beneficial. Harms attributed to antibiot- cific antibiotics. Our findings are consistent with the review on ics were mainly vomiting, diarrhoea, and abdominal pain but antibiotics for chronic purulent rhinitis, and we do not feel that also included rashes and hyperactivity (table). No more serious more randomised controlled trials on this subject are warranted.
harm occurred in the placebo arm in any of the trials, which fits Thus we support the current guidelines in their advice not to use with the clinical notion that this is not a serious condition. At antibiotics but arrive at this point by taking into account the evi- best, a number needed to treat of seven means that six patients dence, the benefits, and the harms of both treating and not treat- get no benefit for every one who gets benefit. Furthermore, the number needed to treat for benefit from antibiotics (7-15) over- Contributors: Both authors reviewed the abstracts resulting from the laps with the number needed to harm (12-78). Our results are search, extracted the data, and wrote the paper. BA did the analysis and is consistent with the Cochrane review of chronic purulent rhinitis, which found a benefit for antibiotics (calculated as a reduced risk Funding: The initial Cochrane review “Antibiotics for the common cold” of persistent purulent rhinitis), with a pooled relative risk of 0.75 (1998) was funded by the Charitable Trust of the Auckland Faculty of the (95% confidence interval 0.61 to 0.92) and a number needed to Royal New Zealand College of General Practitioners. This specific review treat of nine (at the mean control event of 0.46).10 was not funded by any external agency. The authors’ salaries were fromUniversity of Auckland staff funding.
Several of the studies were not of high quality yet scored well Competing interests: BA is a member of the Future Forum, an educational on the Jadad scale. None of the studies used an intention to treat foundation funded by AstraZeneca UK, and a committee member of the analysis, which is not a requirement of the Jadad scale. As various Pharmac seminar series (Pharmac is the New Zealand government funding terms are used for acute purulent rhinitis, we cannot be sure that we retrieved all the relevant articles. We found four of the studiesin our Cochrane review of antibiotics for the common cold.
Steinweg K. Natural history and prognostic significance of purulent rhinitis. J Fam Pract1983;17:61-4.
Although the trend of results is towards an effect of antibiotics, Arroll B, Goodyear-Smith F. General practitioner management of upper respiratory the funnel plot indicates that some publication bias may exist.
tract infections: when are antibiotics prescribed? N Z Med J 2000;113:493-6.
Mainous AG, Hueston H, Eberlein C. Colour of respiratory discharge and antibiotic The studies also used different antibiotics, and the only clearly non-significant study used cefalexin.7 The relative risk from Gonzales R, Barrett PHJ, Steiner JF. The relation between purulent manifestations andantibiotic treatment of upper respiratory tract infections. J Gen Intern Med pooling the two amoxicillin studies was statistically significant, so amoxicillin may be preferred if any antibiotic is to be used.
Snow V, Mottur-Pilson C, Hickner JM. Principles of appropriate antibiotic use for acutesinusitis in adults. Ann Intern Med 2001;134:495-7.
The difference between sinusitis and acute purulent rhinitis is Rosenstein N, Phillips WR, Gerber MA, Marcy M, Schwartz B, Dowell SF. The common not always clear, and involvement of the sinus mucosa in the Todd JK, Todd N, Damato J, Todd WA. Bacteriology and treatment of purulent and 56% of the participants in De Sutter (2002) had unilateral nasopharyngitis: a double blind placebo-controlled evaluation. Ped Infect Dis facial pain.8 In one study of purulent rhinitis of greater than 10 De Sutter AI, De Meyere MJ, Christiaens TC, van Duriel ML, Peersman W, De days’ duration (and therefore excluded from this analysis), all Maeseneer JM. Does amoxicillin improve outcomes in patients with purulent participants had to be free of abnormalities on their facial x rhinorrhea? J Fam Pract 2002;51:317-23.
Turnbridge J, Christiansen K. Antibiotic use and resistance—proving the obvious. Lan- rays.22 In this study, azithromycin was significantly more effective Study or subcategory
Relative risk
Relative risk
(random) (95% CI)
(random) (95% CI)
Total events: 254 (antibiotic), 154 (placebo) Meta-analysis of studies of outcomes of purulent rhinitis at five to eight days, antibiotic versus placebo (Taylor 1977a is co-trimoxazole arm; Taylor 1977b is BMJ Online First
10 Morris P, Leach A. Antibiotics for persistent nasal discharge (rhinosinusitis) in children.
14 DerSimonian R, Laird N. Meta-analysis in clinical trials. Control Clin Trials 1986;7:177- Cochrane Database Syst Rev 2002;(4):CD001094.
11 Arroll B, Kenealy T. Antibiotics for the common cold and acute purulent rhinitis.
15 Howie JG, Clark GA. Double blind trial of early demethyltetracycline in minor respira- Cochrane Database Syst Rev Issue 2005;(3):CD000247.
tory tract illness in general practice. Lancet 1970;i:1099-102.
12 Williams JW Jr, Aguilar C, Cornell J, Chiquette E, Dolor RJ, Makela M, et al. Antibiotics 16 Taylor B, Abbott GD, Kerr MM, Fergusson DM. Amoxycillin and co-trimoxazole in pre- for acute maxillary sinusitis. Cochrane Database Syst Rev 2003;(2):CD000243.
sumed viral respiratory infections in childhood: a placebo controlled trial. BMJ 13 Jadad AR, Moore RA, Carroll D, Jenkinson C, Reynolds JM, Gavaghan DJ, et al. Assess- ing the quality of reports on randomised clinical trials: is blinding necessary? Control 17 Vogt FC. Medical management of purulent rhinitis: a double-blind comparison of vasoconstrictor agent alone with a combination of vasoconstrictor and antimicrobialdrugs. Clin Pediatr 1966;5:547-9.
18 Herne N. Double blinded trial comparing xibornol, tetracycline and placebo in seasonal upper respiratory tract infection. Medicines et Maladies Infectieuses What is already known on this topic
19 Stott NC, West RR. Randomised controlled trial of antibiotics in patients with cough General practitioners often prescribe antibiotics for an and purulent sputum. BMJ 1976;ii:556-9.
20 Sackett D, Straus SE, Richardson S, Rosenberg W, Haynes RB. Evidence-based medicine: acute upper respiratory tract infection when the rhinitis is how to practice and teach EBM. New York: Churchill Livingstone, 2000.
21 Gwaltney JM, Phillips CD, Miller RD, Riker RD. Computed tomographic study of the common cold. N Engl J Med 1994;330:25-30.
22 Haye R, Lingass E, Hoivik HO, Odegard T. Azithromycin versus placebo in acute infec- Most guidelines recommend against using antibiotics for tious rhinitis with clinical symptoms but without radiological signs of maxillary sinusi- this condition, but this advice is based on one study tis. Eur J Clin Microbiol Infect Dis 1998;17:309-12.
What this study adds
Review of seven papers indicates that antibiotics areprobably effective for acute purulent rhinitis Department of General Practice and Primary Health Care, University of Auckland,Private Bag 92019, Auckland, New Zealand This is not a sufficient reason to use antibiotics, however, as no serious adverse events occurred in the placebo group T Kenealy senior lecturerCorrespondence to: B Arroll BMJ Online First


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