US FDA issues guidelines for developing drugs for acute bacterial sinusitis

The US Food and Drug Administration (FDA) has issued guidelines for the pharmaceutical  industry for developing antimicrobials for the treatment of acute bacterial sinusitis (ABS). The FDA stated that any new drug being studied for ABS should have documenting in-vitro antibacterial activity against the most commonly pathogens associated with ABS. These include Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis. Even though animal models of ABS has been developed, particularly for S. pneumoniae infection, they cannot substitute for clinical trials in patients that must be conducted to evaluate drug safety and efficacy. The FDA recommend that two adequate and well-controlled human trials establishing safety and efficacy be conducted for that indication.  However, a single trial for an ABS indication may be appropriate if there is data from other clinical trials demonstrating effectiveness in other respiratory tract diseases such as community acquired bacterial pneumonia. Additional supportive information like pharmacokinetic and pharmacodynamic studies demonstrating concentration of the antibacterial drug in the sinuses at a level expected to be active against the common pathogens causing ABS would be required. Because direct assessment of ABS symptoms to support a conclusion of treatment benefit in response to antibacterial drug therapies is readily measured no surrogate markers of success of therapy are needed. Antimicrobials with clinically significant toxicity would not be considered appropriate for study of ABS unless treatment of a more seriously ill patient population is being considered.

New guideline for the treatment of sinusitis released by the Infectious Diseases Society of America (IDSA).

The new guideline emphasize that the vast majority of sinus infections are caused by viruses and should not be treated with antibiotics. In those cases the new guidelines call for shorter treatment time than older guidance, which suggested a 10 to 14 days weeks of antibiotic treatment for a bacterial infection. The IDSA guideline suggests that five to seven days is long enough to treat  most bacterial infection without encouraging resistance in adults, though children should still receive the longer course.

Because of increasing resistance to amoxicillin (the current standard of care) the guideline recommends amoxicillin-clavulanate as the treatment of choice for acute sinusitis.  Amoxicillin-clavulanate is a combination that helps to overcome antimicrobial resistance by inhibiting an enzyme that breaks down the antibiotic.

The guidelines also recommend against other commonly used antibiotics, including azithromycin, clarithromycin and trimethoprim/sulfamethoxazole, because of growing drug resistance.

Whether the sinus infection is bacterial or viral, the use of decongestants and

antihistamines is not recommended as they may make symptoms worse. Nasal steroids can help ease symptoms as may nasal irrigation using a sterile solution, including sprays, drops or liquid. It is also recommended to use acetaminophen for sinus pain and drink plenty of fluids.

The symptoms of a bacterial sinus infection that does warrant prompt attention and possibly antibiotics are:

1. Symptoms that last for 10 or more days and are not improving, or severe symptoms accompanied by a fever of 102 degrees Fahrenheit or higher

2. Facial pain and green nasal discharge that lasts for 3 or 4 days

3. Symptoms that initially improve after 5 to 7 days, but then return and worsen.

Is amoxacillin an adequate agent for the treatment of sinusitis?

A recent study by Garbutt and associates evaluated the effect of amoxicillin treatment over symptomatic treatments for adults with clinically diagnosed acute sinusitis.

They performed a randomized, placebo-controlled trial of 166 adults with uncomplicated, acute sinusitis between 2006 and 2009. Patients were randomized to receive a 10 days course of either amoxicillin ( 85 patients) or placebo (81 patients). All received a supply of symptomatic treatments for pain, fever, cough, and nasal congestion to use as needed. On day 3 of treatment, there was no difference in improvement between placebo-takers and those prescribed antibiotics. On day 7, the antibiotic group reported a slight improvement that the researchers said was unlikely to represent a noticeable relief in symptoms, but that edge disappeared by day 10, when 80 percent of patients in both groups reported they felt better or cured.

The main problem in this study is that many of the patients included in it may have not suffered from bacterial sinusitis but a viral one rendering amoxicillin useless. Furthermore, amoxicillin is no longer a reliable antimicrobial for the treatment of bacterial sinusitis. This is because many of the pathogens causing bacterial sinusitis have become resistant to it. These include Streptococcus pneumoniae (5-10% highly resistant), haemophillus influenzae (30-40%), Moraxella catarrhalis (>95%) and Staphylococcus aureus (>80%).

The implementation of the 7-valent pneumococcal conjugate vaccine has created a shift in the isolation rate of pathogens causing sinusitis. The proportion of H. influenzae in relation to S. pneumoniae has increased over the years such that currently they are approximately equal ( about 40%). This shift contributes to the therapeutic inefficacy of amoxicillin.

The reduced efficacy of amoxicillin lead a multidisciplinary expert panel of the Infectious Diseases Society of America to generate new guidelines for the treatment of acute rhinosinusits. These guidelines recommend that amoxicillin-clavulanate is preferred over amoxicillin as empiric antimicrobial therapy in adults and children with acute bacterial rhinosinusitis.