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Update on Current Management Strategies for Common Respiratory Tract Infections

The Importance of Accurately Diagnosing Common RTIs

Up to 60% of the patients seen in primary care settings will present with a respiratory tract complaint. Rhino-sinusitis (RS) is defined as an inflammatory response of the mucous membranes in the nasal cavities and paranasal sinuses, fluids in these cavities, or the underlying bone. Several factors may predispose toward RS. Among them are viral upper respiratory tract infections (URTI), immunoglobulin deficiencies, disorders of mucociliary transport and allergies. Obstructions in the sinus ostia may be related to mucous congestion or anatomical obstructions such as septal deviations.

Twenty million cases of acute bacterial rhinosinusitis (ABR) are seen annually and it is the fifth most common diagnosis when antibiotics are prescribed. Expenditures for this disease have been estimated as high as $3.5 billion a year in the United States. (Sinus Allergy Health Partnership. Otolaryngol Head Neck Surg. 2004;130:S1).

Major symptoms of ABR include facial pain or pressure, facial congestion or fullness, nasal obstruction, purulent nasal discharge, diminished or absent olfaction, fever, and purulence in the nasal cavity during examination. The minor factors include headaches, halitosis, fatigue, dental pain, cough, and ear pain, pressure, or fullness. A diagnosis is made by the presence of at least two major or one major and two minor factors, four weeks or less duration, and symptoms worsening after 5 days or persis-ting for more than ten. It resolves completely after therapy (Lanza D et al. Otolaryngol Head Neck Surg. 1997; 117:S1). (Table 1)

“I cannot stress enough the need to examine the nasal cavity,” said Charles A. Moxin, MPAS, PA-C, Vice President, The Association of Family Practice Physician Assistants in San Antonio, TX. “There are a lot of practitioners out there who never take the time to look up someone’s nose. That is an integral part of making the diagnosis.”

Bronchitis is an inflammation of the tracheal bronchial tree that is generally self-limiting with complete healing. It can be divided into two groups. Acute bronchitis is seen in generally healthy individuals. Acute exacerbation of chronic bronchitis (AECB) is linked with chronic obstructive pulmonary disease (COPD) in a patient who already has compromised airways.
Although bacteria can cause bronchitis, roughly 95% of cases are viral (Boldy D, et al. Respir Med. 1990; 84:377).

“This often leads to problems with patients who want an antibiotic,” said Mr. Moxin. “I don’t care how much you explain to your patient, they will not leave your office unless you prescribe them some kind of antibiotic.”

Generally ABR is diagnosed based on history and physical examination. Chest X-rays may be indicated to rule out pneumonia. Sputum cultures should be obtained if a bacterial cause is suspected. Lung function tests, if available, should be done to assess respiratory status.

AECB usually presents as increased coughing, dyspnea, and sputum. There are three types of AECB with Type I having all three symptoms while Type II will present with two. Type III has one of the above plus at least one of the following: URTI in the past five days, fever without other cause, increased wheezing or cough, and increased respiratory or heart rate. They may have acute exacerbations three or four times a year (Anthonisen N et al. Ann Intern Med. 1987;106:196). (Table 2)

“The main thing that can be done to stop this is quit smoking,” said Mr. Moxin. “However, air pollution, occupational exposures, and a persistent history of childhood RTIs are other risk factors.”

Community acquired pneumonia (CAP) is another important RTI. The cardinal symptoms are coughing, increased sputum, pleuritic chest pains, shaking chills, and fever. The diagnosis is made with a history of the cardinal symptoms, physical examination, and diagnostic studies such as chest X-ray, complete blood count, and sputum smears or
cultures.

Typical pathogens include Strepto-coccus, Haemophilus, and Staphy-lococcus pneumoniae. Atypical pathogens include Mycoplasma, Chlamydia, Legionella, and some fungi making it important to culture sputum to confirm the causative organism.

“CAP is the sixth leading cause of death in the U.S,” noted Mr. Moxin. “The incidence and mortality increase after 65 years of age.”


Advancing the Treatment Paradigm in the Treatment of RTIs

“When we prescribe an antibiotic, we consider the patient’s age, allergies, renal and hepatic function, and comorbidities,” said Gregory Volturo, MD, Associate Professor of Emergency Medicine, University of Massachusetts Medical School, Worcester. “We think about costs and frequency and the bugs we want to cover. One thing we don’t think about enough is resistance.”

Resistance is like a balloon, according to Dr Volturo. If you push in one side, another is going to pop out. For example, when levofloxacin is prescribed, that puts pressure on gram-negative organisms and that drives resistance. (Table 1)
Malcolm and colleagues prospectively observed all 768 patients who presented to Edmonton, Alberta hospitals for CAP. The most commonly prescribed antibiotics were azithromycin (36%), levofloxacin (32%), and clarithromycin (17%). Half of the levofloxacin usage was inappropriate according to Canadian Thoracic Association Guidelines (Malcolm C et al. Arch Intern Med. 2003;163:797).

Another study from the University of Pennsylvania showed that 81% of those who received a fluoroquinolone (FQ) were inappropriately prescribed. The more interesting part to Dr. Volturo was that 33% of these patients had no evidence of any infection. In another 14% there was an inability to assess the need for antimicrobial therapy (Lautenbach E et al. Arch Intern Med. 2003;163:601).

“This is a major driver of resistance,” he noted. “It is very hard to get patients out the door without a prescription. The Centers for Disease Control and Prevention (CDC) has a new slogan with posters to put up in the office that say ‘Cough, sniffle, sneeze, no antibiotics please’.”

Of the risk factors for FQ resistance, prior use of the class is the main concern because FQs are so broadly used. If a patient has received an FQ or any other class of antibiotic within the last three to four months and now requires more antibiotic therapy- switch to another class antibiotics as the potential for resistance is high. Other factors for FQ resistance include older age, nursing home residence, beta-lactams, COPD, or nosocomial infections (Ho P et al. Clin Infect Dis. 2001;32:701).

However, all FQs are not the same in resistance. For example, moxifloxacin is a more potent agent against S. pneumoniae and 8% of the isolates resistant to levofloxacin will still be sensitive to moxifloxacin (Loeloff M, et al. Abstracts of the 40th ICAAC. Toronto, Ontario, Canada. 2000. Abstract 2106).

“This does not mean patients who fail levofloxacin should be switched to moxifloxacin, but rather that we should probably start people out on moxifloxacin when we suspect Strep. pneumoniae,” said Dr. Volturo. “But we also need to consider the CDC’s recommendations. These use quinolones in CAP only if they have failed another therapy, there is an allergy to recommended agents, or documentation of a highly resistant infection in order to reduce development of resistance to these agents.”

No matter what is being treated, if a patient fails therapy in one class of medications, they should not be tried next on another medication in the same class.

Where to treat CAP should be based on a three-step process. These are assessing for pre-existing conditions that might compromise their safety in home care, calculating severity of Pneumonia Patient Outcomes Research Team (PORT) Index and using clinical judgment (Mandell LA et al. Clin Infect Dis. 2003;37:1405).

There are currently many entities that have released clinical guidelines for what they think is the appropriate treatments for CAP. The Antibiotic Selection for Community Acquired Pneumonia (ASCAP) panel developed their own set that focused on which drugs to give under what circumstances.

For those who are being treated on an outpatient basis and are otherwise healthy, the first drug of choice is azithromycin. Moxifloxacin is the preferred FQ if needed. If the person has a comorbid condition, moxifloxacin is preferred over the other FQs and clarithromycin.

For in-hospital management, the panel suggested combination therapy with IV ceftriaxone and IV azithromycin as first-line. For monotherapy, moxifloxacin IV is the top choice with IV levofloxacin or gatifloxacin as alternates.

If patients are sicker and in an Intensive Care Unit (ICU), IV ceftriaxone with either IV levofloxacin or IV moxifloxacin should come to the front. IV azithromycin is a possible choice, but the sicker a patient is, the more likely they are to be resistant, according to Dr. Volturo.

A study by Waterer and others looked at the efficacy of dual effective therapy versus single effective therapy in a retrospective study of 225 patients over 55 months. The two-week mortality was significantly lower in those who received two medications (Waterer G et al. Arch Int Med. 001;161:1837).

The time-to-delivery of antibiotics also plays an important role in this population. Meehan and colleagues found a significant reduction in those who were given antibiotics within 8 hours of diagnosis. Mortality was increased for every hour of delay (Meehan T et al. JAMA. 1997;278:2080).

“The largest jump in deaths was between two and four hours, which lead us to recommend that all patients start antibiotics within four hours of diagnosis,” said Dr. Volturo. (Figure 1)

While in-patient there will come a time when a switch from IV to oral medication will be needed. With FQ, there is no problem because bioavailability is the same for both forms. Azithromycin monotherapy is suitable at 500 mg a day for 7 to 10 days from initiation of IV therapy.

About 90% of the time, the common cold results in rhinosinusitis and only about 2% progress to bacterial sinusitis. However, there is an almost complete overlap of symptoms to confuse the picture clinically.

The indicators for bacterial infection include symptoms for more than 7-10 days, symptoms worsening after 5-7 days, or severe symptoms at any time. Others include purulent nasal secretions, pain in the upper teeth, pain on bending forward, elevated erythrocyte sedimentation rate, and increased C-reactive protein (Lanza D et al. Otolaryngol Head Neck Surgery. 1997;117:S1).

“Before therapy, we have to consider risk stratification because our treatments will change based on this,” he said. “Those at lower risk have been generally healthy, have mild to moderate symptoms and no recent antibiotic use. High-risk patients have comorbid conditions, have moderate to severe symptoms and have been on antibiotic therapy recently so are more likely to be resistant.” (Table 2)

The first-line antibiotic therapies for mild sinusitis from American Association of Otolaryngologists (AAO) guidelines are amoxicillin for 10-14 days, amoxicillin/clavulanate for ten days, or azithromycin for three (Sinus Allergy Health Partnership. Otolaryngol Head Neck Surgery. 2004;130:S1).

“I am not a fan of cefuroxime because of Strep. pneumoniae resistance rates approaching 40% in some parts
of the country,” said Dr. Volturo. “Cefpodoxime is a good drug but expensive and up to 80% of these patients have bugs that produce beta-lactamases. Doxycycline is a good choice if cost is a concern, followed by macrolides and ketolides.”

Alternatives should be considered if a patient has been treated with antibiotics in the last three months, there is a failure to improve within 72 hours, or they are in a high-risk population.

“If you are going to use amoxicillin, you have got to use a big dose twice a day for up to 14 days,” said Dr. Volturo. “Three days of azithromycin therapy have been shown to be just as effective as two weeks of amoxicillin/clavulanate.”

Alternative first-line antibiotics would include moxifloxacin, levofloxacin, clarithromycin and doxycycline. These would be used for patients allergic to the other first-line drugs.

Under the AAO Guidelines, the treatment of moderate RS should begin with FQ therapy, especially in those with comorbid conditions. The medications specifically suggested include gatifloxacin, levofloxacin, moxifloxacin or ceftriaxone. Amoxicillin/clavulanate is an accepted combination therapy. For tertiary treatment, ceftriaxone or combination therapy to cover for gram-positive organisms (amoxicillin or clindamycin) and gram-negative organisms (cefixime) is suggested. Adjunctive therapy includes rest, fluids, nutrition, antihistamines, decongestants, nasal steroids and expectorants.

“I do not recommend long-term antihistamines,” stressed Dr. Volturo. “They are great in the early phases since they get rid of sneezing as well as the itchy and watery eyes. With time, they dry up the mucosa and end up causing mucous plugging.”

Risk factors for complications include recurrent acute sinusitis, uncontrolled asthma, nasal polyps, cystic fibrosis, poorly controlled diabetes, and the immunocompromised. These are also indications for referral to an appropriate specialist.
Referral should be done immediately if the patient has periorbital cellulitis or abscess, visual disturbance or loss, meningitis or brain abscess, invasive fungal sinusitis, uncontrolled bleeding, bone destruction or unexplained mass or tumor. Surgery may be an option in those with chronic refractory sinusitis, recurrent acute sinusitis, suppurative complications, fungal sinusitis or nasal obstructions.

AECB presents with another set of symptoms including increased dyspnea, sputum purulence and volume. Treatment should be pointed toward returning the patient to baseline, minimizing the risk for failure and relapse, reducing the need for additional antibiotic therapy, and extending the time between exacerbations.

The general treatment options include beta-agonists, anticholinergic medications, home oxygen, systemic
corticosteroids, and antibiotics. Theophylline may be an option, although there is currently much controversy surrounding its efficacy. Home oxygen should be used with caution since many patients may be CO2 retainers and added oxygen could suppress their hypoxic drive.

Trials have shown that use of steroids for short periods can increase exacerbation-free time. Results of the Systemic Corticosteroids in Chronic Obstructive Pulmonary Disease Exacerbations (SCCOPE) Trial showed no reason to continue steroids past two weeks (Aaron S et al NEJM. 2003; 348:2618; Niewoehner D et al NEJM 1999;340:1941).

“Nobody has quite yet put the antibiotic picture together,” said Dr. Volturo. “Part of the reason is that the COPD population is a heterogeneous mix. There is also difficulty in distinguishing colonization from infection in this group.”

What is known is that antibiotics are associated with lower relapse rates in ambulatory AECB. A study by Adams et al. showed that the relapse rate with no antibiotics was significantly greater than those who got antibiotics. A meta-analysis by Saint and colleagues including studies between 1950 and 1992 found that eight out of 10 favored antibiotic use (Adams S et al. Chest. 2000;117: 1345; Saint S et al. JAMA. 1995;274: 1131).

“Antibiotic choices are going to vary based on the severity of exacerbation risk factors,” noted Dr. Volturo. “The sicker somebody is, the more the microbiology changes.”

The Canadian Thoracic Society recently presented AECB therapy guidelines that break patients into three categories. They include simple bronchitis, complicated chronic bronchitis, and chronic suppurative bronchitis. The latter category is at risk for Pseudomonas aeruginosa infections (O’Donnell D et al. Can Res. J. 2003:10 (suppl B):1B) .

Those patients of any age who have less than four exacerbations a year, no cardiac disease and FEV1 >50%, have simple chronic bronchitis. Recommended antibiotic treatment is a macrolide (azithromycin, clarithromycin), one of the 2nd or 3rd generation cephalosporins, or amoxicillin.

“If you use azithromycin, it is 500 mg for three days,” said Dr. Volturo. “I like single-dose therapy for shorter periods of time because that is when we know the patient is going to be the most compliant.”

Complicated bronchitis is seen in those 64 years or older, more than four exacerbations a year, have current serious cardiac disease, FEV1< 50%, are on home oxygen, have been prescribed oral steroids, and have had an antibiotic within the last three months. The suggested treatment in this case is use of FQs or amoxicillin/clavulanate. Keep away from what has been prescribed recently to lessen the pressure on that medication.

The diagnosis of chronic suppurative bronchitis is made when patients have chronic bronchial secretions, there is chronic corticosteroid therapy, antibiotics are used more than four times a year, and the FEV1 is less than 35%. In this case, the medications used should be carefully targeted to the results of cultures. Use of ciprofloxacin empirically for P. aeruginosa is acceptable. Hospital-ization for parenteral treatment should be considered.

“Antibiotics and adjuvant therapy are very important in all patients with respiratory tract infections,” said Dr. Volturo. “Practitioners need to consider resistance and compliance in addition to risk factors when deciding on which medication to prescribe.”

 

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