- Understand the indications for
antibiotic treatment in acute sinusitis.
- Recognize the potential harms of
inappropriate antibiotic prescribing for individual patients and
the population at large.
- Review the evidence on the effectiveness
of quality improvement efforts to reduce inappropriate antibiotic
A healthy 53-year-old woman presented to her
primary care physician with upper respiratory symptoms and possible
sinusitis. She was prescribed Augmentin (amoxicillin-clavulanate).
Despite this therapy, her symptoms persisted. She was then
Upper respiratory tract infection (URI) symptoms
are among the most common presenting complaints to primary care
physicians, with 83.1 million visits occurring in 2002
, of which 3.1 million
were ultimately ascribed to acute sinusitis in adults.(2)
Sinusitis occurs after or in conjunction with a viral URI.
Inflammation of the respiratory epithelium lining the paranasal
sinuses (most commonly the maxillary sinuses) leads to obstruction
of the sinus ostia and accumulation of mucus within the sinuses.
The adjacent nasal mucosa is invariably inflamed as well. This
process leads to the typical sinus symptoms of headache, nasal
congestion and discharge, and facial pain or pressure, sometimes
accompanied by sneezing, toothache, or fever.
Most cases of acute sinusitis are caused by
viruses, and only 0.5%–2% of cases of viral sinusitis develop
into a bacterial infection.(3)
However, distinguishing viral from
bacterial sinusitis on clinical grounds is difficult, as no single
symptom or physical examination finding has been found to be
predictive of bacterial sinusitis. The typical symptoms of
sinusitis—headache and nasal congestion—do not reliably
predict bacterial infection, and imaging studies (such as CT scan
or plain radiographs of the sinuses) are frequently abnormal in
both viral and bacterial sinusitis. In 2001, the Centers for
Disease Control and Prevention (CDC) recommended that acute
bacterial rhinosinusitis be diagnosed only when a patient has three
clinical criteria (4):
• Maxillary pain
or tenderness in the face or teeth.
Mucopurulent nasal discharge.
• Symptoms have
lasted for 7 days or more.
In addition, worsening of symptoms after initial
improvement appeared to be moderately predictive of bacterial
infection in some studies. A 2007 practice guideline by the
American Academy of Otolaryngology—Head and Neck Surgery
generally corroborated the CDC guidelines.(5)
guidelines recommend amoxicillin as the preferred initial
antibiotic when antibiotics are warranted, as most cases of
bacterial sinusitis are caused by Streptococcus
pneumoniae, Haemophilus influenzae, or Moraxella
Despite these guidelines,
overtreatment of acute sinusitis with antibiotics is common. A 2007
study found that antibiotics were prescribed in 82.7% of outpatient
visits due to acute sinusitis.(2)
Many of these prescriptions are unnecessary, as the vast majority
of cases of sinusitis are viral in origin—especially when
symptoms have lasted for less than 1 week.
In this case, the primary care
physician should have asked the patient about the duration of
symptoms, character of nasal discharge, and presence of toothache,
and examined her for evidence of tenderness over the maxillary
sinuses. Antibiotic treatment with amoxicillin would have been
justified if the three clinical criteria above were present. If
antibiotics were not warranted, management should have focused on
symptomatic therapy, including decongestants and antiinflammatory
The patient was prescribed
Augmentin (amoxicillin-clavulanate) as initial therapy. While this
agent is the second most common antibiotic prescribed for acute
sinusitis (behind amoxicillin) (2)
, its choice in
this scenario illustrates another facet of inappropriate antibiotic
use: prescribing of broad-spectrum agents when narrow-spectrum
antibiotics are indicated. The use of broad-spectrum antibiotics
rose significantly during the 1990s. For sinusitis, prescribing of
broad-spectrum agents increased from less than 20% (of cases where
antibiotics were prescribed) in 1991 to more than 40% in
Both amoxicillin-clavulanate and azithromycin are considered
broad-spectrum antibiotics, and neither has been demonstrated to be
significantly more effective at curing sinusitis compared with
amoxicillin. Even if antibiotics had been warranted in this
case—which is unlikely—treatment should have consisted
of amoxicillin along with symptomatic therapies. A second
antibiotic course could be justified only if infection with a
resistant organism was suspected, which would be unlikely in a
previously healthy patient with no recent history of antibiotic
Shortly after starting her second course of
antibiotics, the patient began feeling unwell. A few days later,
she was found down in her home by her daughter. The patient was
brought to the emergency department for evaluation. Her work up
revealed profound anemia due to brisk autoimmune hemolysis. This
was thought to be due to the amoxicillin-clavulanate she had
received. She was started on high-dose immunosuppressive therapy
Although antibiotics have yielded undeniable
benefits for patients since their introduction into medical
practice, inappropriate use of these agents results in adverse
effects for both individuals and the population at large.
Beta-lactam antibiotics such as amoxicillin are generally quite
safe, but prescribers and patients must be aware of a wide range of
potential adverse effects, ranging from common problems like
antibiotic-associated diarrhea (which can occur in up to 34% of
patients receiving a typical course of amoxicillin-clavulanate), to
rare but dangerous reactions such as Clostridium difficile
colitis, anaphylaxis, or this patient's problem: autoimmune
hemolysis. Many antibiotics may cause drug-induced autoimmune
hemolytic anemia; in the case of penicillins, the mechanism is
generally via formation of drug-specific IgG antibodies in the
patient's serum, resulting in a direct antiglobulin (Coombs')
positive hemolytic anemia.(7)
Amoxicillin was first recognized as a cause of autoimmune hemolytic
anemia more than 2 decades ago.(8)
Although mild cases may be managed by withdrawal of the antibiotic,
cases of severe symptomatic anemia require treatment with high-dose
glucocorticoids, as in this patient.
The chief population-level effect of antibiotic
overuse is the widespread and growing problem of antimicrobial
resistance (AMR). AMR is a worsening problem among many bacteria,
including Staphylococcus aureus, Streptococcus
pneumoniae, and Escherichia coli—organisms that
cause common clinical syndromes such as cellulitis,
community-acquired pneumonia, and urinary tract infection. Once
confined to hospitals, these drug-resistant pathogens are becoming
increasingly prevalent in the community setting, and some data
indicate that prior treatment with antibiotics may increase an
individual patient's likelihood of contracting an infection with a
drug-resistant bacteria.(9) AMR
exerts significant societal costs, as infections with
drug-resistant bacteria are associated with increased morbidity,
mortality, and health care expenditures.
Antibiotic use leads to AMR by
two mechanisms: creation of a susceptible host by eliminating an
individual's normal bacterial flora and selective pressure
promoting survival of bacterial strains with genetic mutations that
confer antibiotic resistance.(10)
Due to this close
link between antibiotic prescribing and development of AMR,
extensive national and international efforts (11)
have focused on
reducing antibiotic prescribing for conditions in which antibiotics
are not usually indicated. The CDC's "Get Smart" campaign is a
A major focus of
these efforts is reducing antibiotic prescribing for acute
respiratory infections (ARIs), including sinusitis, as these
infections are rarely bacterial in origin.
The patient's hospital course was marked by
multiorgan failure, septic shock, and spontaneous bowel perforation
requiring hemicolectomy. Examination of the bowel showed
Aspergillus, leading to a diagnosis of disseminated
aspergillosis. Despite aggressive antifungal therapy, the patient
ultimately succumbed to overwhelming infection and died.
This patient suffered a tragic outcome likely
related to inappropriate prescribing of antibiotics. While the
complications and ultimate outcome of this case are exceedingly
rare, unfortunately, the problem of inappropriate antibiotic
prescribing remains common. Over the past decade, antibiotic
prescribing for ARIs has decreased in response to publicity and
education regarding antimicrobial resistance. However, prescribing
rates for viral infections remain high: in 2002, nearly half of
adults with nonspecific ARIs were still prescribed
Limited success in reducing overall antibiotic prescribing may be
counteracted by a marked increase in prescribing of broad-spectrum
antibiotics, the use of which doubled during the
A clinician's decision to prescribe antibiotics
is the result of several factors, including patient factors
(patients often expect to be prescribed antibiotics to treat
respiratory infections), physician factors (physicians often use
heuristics to judge if antibiotics are
warranted, rather than relying on evidence-based criteria), and
health care system factors (requiring prior approval for acute
appointments may result in fewer visits for respiratory symptoms,
and correspondingly fewer antibiotic prescriptions).(10)
Quality improvement (QI) efforts to reduce inappropriate antibiotic
prescribing have used various methods to educate patients and
clinicians on indications for antibiotic prescribing. Providing
targeted feedback to clinicians on their prescribing practices has
also been used. Community-wide campaigns, using mass media
communications and other strategies to simultaneously target
patients and clinicians, are underway in several European countries
and US states.
Reviews of published QI efforts show them to be
moderately effective in reducing inappropriate prescribing and
reducing unnecessary broad-spectrum antibiotic use.(10, 14)
While no single strategy appears uniquely effective, promising
strategies include mass media campaigns in combination with
targeted clinician education and use of explicit clinical decision
support algorithms to indicate when antibiotic prescribing is
appropriate. A decision support system could have been very useful
in this case. In such a system, the clinician would have been
prompted to enter the patient's presenting symptoms and signs, and
the system would provide patient-specific treatment
recommendations. A recent cluster-randomized trial using a handheld
computer–based decision support system for prescribing in
respiratory infections accomplished significant community-wide
reductions in antibiotic use in communities in Utah and
Antibiotic prescribing for respiratory symptoms
is frequently driven by a physician's desire to respond to a
patient's explicit (or implied) request for
However, research has shown that even patients who explicitly
request antibiotics are satisfied if clinicians directly address
their concerns by explaining the rationale for not prescribing
antibiotics and offer symptomatic therapy instead.(17)
efforts to reduce antibiotic prescribing have not caused increased
dissatisfaction with care.(10)
The tragic clinical outcome of
this case is undoubtedly rare, but if inappropriate antibiotic
prescribing continues unchecked, the societal costs may be equally
dramatic. The marked rise in infections caused by
methicillin-resistant Staphylococcus aureus (MRSA)
one example of the clinical implications of drug-resistant
bacteria—a problem that will undoubtedly worsen if
indiscriminate antibiotic use continues. Despite some successes,
inappropriate antibiotic prescribing remains widespread, and
clinicians must take responsibility for improving their prescribing
practices. Although on the surface this case may appear to be an
example of "cascade iatrogenesis" (19)
than a true medical error, failure to adhere to evidence-based
treatment guidelines is increasingly being treated as an
burden of responsibility lies on clinicians to practice judicious
antibiotic prescribing in order to avoid considerable health
implications for their patients in the future.
- Inappropriate antibiotic prescribing
remains common, especially for acute respiratory infections.
- Clinicians should follow evidence-based
treatment guidelines for sinusitis.
- Community-wide campaigns and clinician
decision support systems show promise as means of addressing the
overprescribing of antibiotics.
Sumant Ranji, MD
Assistant Clinical Professor, Division of Hospital Medicine
University of California, San Francisco
Faculty Disclosure: Dr. Ranji has
declared that neither he, nor any immediate member of his family,
has a financial arrangement or other relationship with the
manufacturers of any commercial products discussed in this
continuing medical education activity. In addition, his commentary
does not include information regarding investigational or off-label
use of pharmaceutical products or medical devices.
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