Antibiotics May Not Be Needed for
Acute Rhinosinusitis CME
Clinical Context
Sinusitis accounts for approximately
1 in 5 antibiotic prescriptions in the United States, according to the authors
of the current study. This finding is somewhat surprising considering that
antibiotics have demonstrated mixed results in clinical trials of patients with
acute rhinosinusitis. Although objective findings such as radiographic imaging
appear to be improved with antibiotics, antibiotics appear to have a minimal
effect on clinical symptoms, in part because of rates of spontaneous
improvement of rhinosinusitis, which approach 70%.
The current study by Garbutt and
colleagues further examines the efficacy of antibiotics for acute
rhinosinusitis in a randomized trial based in primary care offices.
Study Synopsis and Perspective
Most symptoms of acute sinusitis
resolve just as quickly without antibiotics as they do with antibiotics,
according to results of a new study
in the February 15 issue of the Journal of the American Medical Association.
Jane M. Garbutt, MBChB, from the
Division of General Medical Sciences at Washington University School of
Medicine in St. Louis, Missouri, and colleagues conducted a randomized
controlled trial in which they compared quality of life improvement in patients
given a 10-day course of amoxicillin vs patients given a placebo.
"Considering the public health
threat posed by increasing antibiotic resistance, strong evidence of symptom
relief is needed to justify prescribing of antibiotics for this usually
self-limiting disease," the authors write.
Rhinosinusitis vs Common Cold
The study included 166 adult
patients from 10 primary care offices in St. Louis, Missouri. Patients were
eligible for the study if they met the diagnostic criteria for acute bacterial
rhinosinusitis from the Centers for Disease Control and Prevention and if they
rated their symptoms moderate, severe, or very severe.
Patients also had to have a history
of maxillary pain or tenderness in the face or teeth, purulent nasal discharge,
and rhinosinusitis symptoms for between 7 and 28 days that were neither
improving nor worsening, or rhinosinusitis symptoms for 7 days or fewer that
first improved and then worsened.
"A lot of the other studies are
including people who just have a cold, instead of a real bacterial sinus
infection. They used a more rigorous definition here that corresponds to
guidelines from the American Academy of Family Physicians and the American
College of Physicians," said Richard M. Rosenfeld, MD, MPH, professor and
chairman of otolaryngology at SUNY Downstate Medical Center, Brooklyn, New
York, in a telephone interview with Medscape Medical News. Dr. Rosenfeld
was not involved with the study.
"The added twist on this study
is they focused on quality of life," said Dr. Rosenfeld.
Study Medications
Patients assigned to the treatment
group (n = 85) received amoxicillin 1500 mg/day in 3 divided doses for 10 days.
Patients assigned to the control group (n = 81) received a placebo.
All study participants were given a
5- to 7-day supply of symptomatic treatments, unless their physician felt the
treatments were contraindicated. The treatments provided were acetaminophen 500
mg every 6 hours as needed for pain or fever; guaifenesin 600 mg every 12 hours
as needed to thin secretions; dextromethorphan hydrobromide 10 mg/5 mL and
guaifenesin 100 mg/5 mL every 4 to 6 hours as needed for cough;
pseudoephedrine-sustained action 120 mg every 12 hours as needed for nasal
congestion; and 0.65% saline spray, 2 puffs per nostril as needed.
The researchers assessed the effect
of treatment on disease-specific quality of life at day 3 as the primary
outcome. They used the modified Sinonasal Outcome Test-16 (SNOT-16) to measure
severity and frequency of 16 sinus-related symptoms over the prior few days.
Items assessed by the SNOT-16 tool included physical symptoms like runny nose,
cough, and ear fullness, as well as quality-of-life factors including
difficulty sleeping, trouble concentrating, and reduced productivity.
Both study groups reported high use
of symptomatic treatments (92%; 95% confidence interval [CI], 88% - 96%).
Quality-of-Life Improvement
The mean change in SNOT-16 scores
for quality of life was similar in both groups at day 3 (treatment group: 0.59
[95% CI, 0.47 to 0.71]; control group: 0.54 [95% CI, 0.41 to 0.67], P =
.69; mean difference between groups, 0.03 [95% CI, −0.12 to 0.19]).
The mean improvement in
quality-of-life scores was similar for both groups at day 10 as well (mean
difference between groups, 0.01 [95% CI, −0.13 to 0.15]). The mean improvement
in quality-of-life scores differed between the groups at day 7, with more
improvement reported by the amoxicillin group (mean difference between groups,
0.19 [95% CI, 0.024 to 0.35]).
Symptom improvement was not
significantly different between the 2 groups at day 3 (37% for the amoxicillin
group vs 34% for the control group; P = .67) or at day 10 (78% for the
amoxicillin group vs 80% for the control group; P = .71). More patients
in the amoxicillin group reported symptom improvement at day 7 (74% for
amoxicillin group vs 56% for control group, P =.02; number needed to
treat = 6 [95% CI, 3 to 34]).
"In this study, retrospective
assessment of change in sinus symptoms suggested that antibiotic treatment may
provide more rapid resolution of symptoms for some patients by day 7. However,
when improvement was assessed as the difference in SNOT-16 scores, the
statistically significant benefit at day 7 was too small to represent any
clinically important change," the authors write.
Resistant Organisms?
Dr. Rosenfeld suggested that the
lack of an antibiotic effect may have been a result of antibiotic-resistant organisms.
He pointed out that amoxicillin is a very common first-line antibiotic for
treating bacterial infections. Two of the 3 main bacteria that cause sinus
infections — Haemophilus influenzae and Moraxella catarrhalis —
can be resistant to penicillin- and amoxicillin-type drugs. Streptococcus
pneumoniae can also be resistant, he explained.
"In the discussion section [the
authors] provide some data that in their community the resistance levels of Streptococcus
pneumoniae to amoxicillin are low. They don't mention anything about
resistance to the other bacteria," Dr. Rosenfeld said.
"[If you] have a sinusitis
caused by one of the penicillin- or amoxicillin-resistant germs, clearly you're
not going to see a benefit of treating with amoxicillin; that's basically the
same as giving a placebo," he added.
If the investigators had used an
antibiotic like amoxicillin clavulanate, which covers a broader spectrum of
bacteria, they may have seen a bigger benefit. "Whether we can extrapolate
this study outside of the St. Louis area or to other antibiotics is very
unclear, and they may have missed the benefit of using a broader spectrum of
antibiotic," he explained.
"Do I think they missed a
dramatic benefit? No, but they may have missed some smaller benefit of using other
antibiotics," said Dr. Rosenfeld.
"Evidence from this study
suggests that treatment with amoxicillin for 10 days offers little clinical
benefit for most patients with clinically diagnosed uncomplicated acute
rhinosinusitis," the authors write. "It is important to note that
patients with symptoms indicative of serious complications were excluded from
this trial and likely need a different management strategy," they
conclude.
One of the study coauthors, Jay F.
Piccirillo, MD, reports that he has grants pending with the National
Institutesof Health, the Department of Defense, and the Federal Emergency
Management Agency; has received honoraria from Emory University and New York
University for invited speaker positions for grand rounds; has received royalties
for the Sinonasal Outcome Test; and is chair of data and safety monitoring
boards for Apnex Medical and the National Institutes of Health, National
Institute on Deafness and Other Communication Disorders. No other author
reported potential conflicts of interest. Dr. Rosenfeld has disclosed no
relevant financial relationships.
JAMA. 2012;307:685-692.
Study Highlights
- The study was conducted in 10
primary care offices in Missouri. Patients eligible for study
participation were between the 18 and 70 years old and had no history of
recent exposure to antibiotics or medical history that would predispose
them to complicated rhinosinusitis. - Cases of rhinosinusitis in the
study were supposed to reflect moderate to severe illness. All
participants had at least 7 days of facial pain and purulent nasal
drainage, or less than 7 days of symptoms with significant worsening after
initial improvement. - Participants were randomly
assigned to receive amoxicillin 500 mg 3 times daily or matching placebo
for 10 days. - All participants also received
5- to 7-day supplies of multiple medications for symptomatic relief. - The primary study outcome was
disease-specific quality of life at day 3 of treatment. This treatment
point was chosen given the high rate of spontaneous resolution of
rhinosinusitis. A validated instrument was used to measure the primary
study outcome. - Other study outcomes included
disease-specific quality of life at days 7 and 10 of treatment, patient
symptoms, patient satisfaction with treatment, rates of relapse and
recurrence of rhinosinusitis, and adverse events associated with study
therapy. - 166 participants underwent
randomization, and baseline data were similar in comparing the amoxicillin
group vs the placebo group. The median age of participants was 32 years,
and 64% were women. The mean duration of rhinosinusitis symptoms exceeded
11 days, and more than 90% of participants had tried symptomatic treatment
before coming to the clinician's office. - Nearly 90% of participants
completed the study treatment in both randomly assigned groups, and 92% of
participants used the supplied medications to relieve symptoms during the
treatment period. - Disease-related quality of life
was similar in comparing the amoxicillin group vs the placebo group at 3
days and at 10 days. There was a small benefit for amoxicillin in this
outcome at day 7, but the study authors state that this difference is of
questionable clinical significance. - Similarly, there was no
difference between groups in symptom improvement at days 3 and 10. 74% of
participants receiving amoxicillin reported symptom relief at day 7 vs 56%
of the placebo group (P = .02). - Subgroup analysis based on
treatment completion and the duration of symptoms corroborated the main
study findings. - Patient satisfaction with
treatment and rates of relapse or recurrence of rhinosinusitis were also
similar between the groups, as was the rate of absence from work. - Rates of adverse events were
also similar in the amoxicillin group and the placebo group. - The only factor associated with
a higher rate of treatment success at day 7 with amoxicillin vs placebo
was nasal obstruction.
Clinical Implications
- Although antibiotic
prescription rates for acute rhinosinusitis are high in the United States,
antibiotics are more associated with improvement in measurements such as
sinus radiographic results compared with patient symptoms. Acute
rhinosinusitis has a high rate of spontaneous improvement. - The current study by Garbutt
and colleagues demonstrates that amoxicillin offered limited clinical
benefit vs placebo among adults with acute rhinosinusitis.
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