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Acute Respiratory Tract Infection Paper

Acute Respiratory Tract Infection Paper

Acute Respiratory Infections
​What is Influenza

Influenza is caused by a virus that attacks mainly the upper respiratory tract – the nose, throat and bronchi and rarely also the lungs. The infection usually lasts for about a week. It is characterized by sudden onset of high fever, myalgia, headache and severe malaise, non-productive cough, sore throat, and rhinitis.Acute Respiratory Tract Infection Paper


How it is spread 
​​​Influenza like illness otherwise known as Acute Respiratory Infection (ARI) is an acute viral infection that spreads easily from one person to another. It can affect anybody in any age group. It usually causes annual epidemics that peak during winter in temperate regions.  Acute Respiratory Tract Infection Paper
The World Health Organization​ recommends vaccination as the most important measure to combat ARIs. ARI Impact on Children
In children influenza poses a serious risk which can lead to severe complications of underlying diseases, pneumonia and death.​ Acute respiratory infection is the most common acute infection in children in every continent. According to Jamison et al. (2006)​ ARIs and particularly Lower Respiratory Tract Infections are responsible for 1.9 million and 2.2 million childhood deaths globally.

In addition to its impact on child death infection with influenza (Flu) has been shown to impair children’s attention and reaction time. It also affects hand-eye coordination and reduces the ability to tolerate high levels of noise, leading to children being distracted from learning activities.

In addition to environmental factors, Vitamin A deficiency​ can lead to promotion of respiratory infections by damaging the lungs and thus reducing resistance.

Upper respiratory infections are more common during the fall and winter. This may be due colder weather and lower humidity levels. Viruses are more active during these times of low humidity. People are also more susceptible during these types of weather conditions. The best course of prevention is to wash your hands frequently and get your flu shot. This is by no means a fail safe. If you are experiencing an upper respiratory infection, the best treatment is to stay hydrated and get plenty of rest.

The term upper respiratory infection refers to an infection of your upper respiratory tract. This includes your nasal passages, sinuses, and upper airways. The symptoms are usually short lived. The typical length of infection is around fourteen days. This is because the main cause of upper respiratory infections is viral in nature. However, prolonged illness may be cause to seek medical attention. Secondary infections caused by bacteria can lead to a more protracted illness of greater than two weeks. Children and the elderly are also at greater risk for complications. Medical intervention may become necessary for these groups of people. Here are some of the signs and symptoms that you may experience during an upper respiratory infection.Acute Respiratory Tract Infection Paper

1. Nasal Congestion

The first few days of an upper respiratory infection generally involve nasal congestion. You may have an overall stuffy feeling or it can be more painful. Swelling in the nasal passages causes this stuffy feeling. Your sinuses are irritated by the infection. This can lead to trouble breathing. You can use a nasal strip in order to open up the nasal passages. This may help you to get some much needed rest. Congestion that is painful is due to the buildup of mucus in the sinus cavities. This condition can typically be relieved by using a decongestant.

It isn’t recommended to give young children cold medication. There are natural remedies that you can try for your kids. You can use a humidifier to help with reducing this congestion. Other solutions are to clear out the sinuses with a saline spray. It may even be helpful to sleep propped up on a pillow. This may relieve some of the discomfit associated with nasal congestion. For severe pain, using a pain reliever may be beneficial for kids. This congestion can be brief or may last a few days before the sinuses start to release the mucus. This leads into the next sign of an upper respiratory infection.

This is the time of year when respiratory tract infections act up, so we’ve created a brief guided tour to the common cold and four of its fellow misery makers. Please refer to the illustration as you read along. Flu is not included because the focus is on anatomical locations in the respiratory tract, and flu’s effects are widespread. A couple of themes emerged as we put this article together. First, it’s true: washing your hands may be your best defense against respiratory infection. Second, antibiotics are important arrows in the treatment quiver, but they’ve been overused, especially for sinusitis and bronchitis.Acute Respiratory Tract Infection Paper

1. Common cold

What is it? Inflammation of the mucous membranes that line the nose.

Symptoms. The medical term, viral rhinitis, may not be so familiar, but the symptoms are a stuffed-up and runny nose and sneezing. About half the time a cold causes a sore or scratchy throat, and that’s often the first symptom, although by the second or third day, the nasal problems predominate. If a cough develops, it may not start until several days after the rest of the symptoms get going and may linger for several weeks after they are gone. Adults rarely have fever with colds — the absence of fever is one way to tell it’s a cold — but children sometimes do.

Causes. Over 200 different types of viruses have been linked to colds, but they all produce similar symptoms. That’s partly because symptoms come from a general immune response to an infection of the respiratory tract, not direct damage that might be the signature of certain viruses. Between 30% and 50% of colds are caused by rhinoviruses. Among the many other types of viruses that cause colds are the viruses that cause influenza (the flu).Acute Respiratory Tract Infection Paper

Prevention. Washing your hands regularly is the single best way to keep from getting a cold (and every other sort of upper respiratory infection). Most often, we pick up the cold-inducing viruses by touching infected people or surfaces, such as doorknobs or banisters, and then infect ourselves by touching our nose or our eyes. (Cold viruses live in airborne droplets released when people cough or sneeze, so it’s possible to get infected by breathing in those droplets directly, but more often our hands are involved.) The research results for high doses of vitamin C have been mixed. Echinacea has been a bust in prevention studies; ginseng a little less so, but it’s hardly a sure thing.

Treatment. The cure for the common cold remains mythically elusive, so for now, treatment is about taming symptoms. Even that less ambitious grail seems out of reach at times. The cough suppressants in many over-the-counter cold medicines haven’t proved to be any more effective than placebos in clinical trials. Phenylephrine isn’t as effective as pseudoephedrine, the nasal decongestant it replaced in many over-the-counter medicines. Nasal inhalers like ipratropium bromide (Atrovent) can help, but overuse of sprays like oxymetazoline (Afrin) is a problem. Echinacea and vitamin C haven’t fared well in treatment clinical trials. The results for zinc have been inconsistent; if it has any effect, study results suggest it’s likely to be quite modest. In the end, you might be best off following the tried-and-true advice: drink plenty of fluids, get lots of rest — and wait it out.Acute Respiratory Tract Infection Paper


Five respiratory tract infections

2. Sinusitis

What is it? Inflammation of the membranes lining the sinuses.

Symptoms. Uncomfortable pressure in the face that feels painful is the telltale symptom. The location varies with the sinuses involved; for example, pain in the forehead is an indication that the frontal sinuses are affected, and if it’s in the upper jaw and teeth, the maxillary sinuses in the cheeks. Like a cold, sinusitis causes nasal congestion because of excess mucus production and swollen nasal membranes. Indeed, sinusitis often feels like a cold that just won’t go away. The mucus is often thick and yellow or green (it turns green because of the large quantities of white blood cells, which, despite their name, give off a green color). Some of the mucus may flow back into the throat — this is the infamous postnasal drip — and cause a bad taste, a cough, or bad breath. Some people also get feverish and fatigued as their bodies mount an immune response.

Causes. Your sinuses are like little caves in the bones around your eyes and nose. They’re lined with membranes that produce thin, watery mucus that drains through tiny openings called ostia. If those ostia get blocked, fluid and mucus build up, creating a nice, cozy place for bacteria, which are naturally present, to multiply. The body responds to the increased numbers with inflammation and swelling that produces the painful pressure and other symptoms. Colds are the most common reason ostia get plugged up in the first place, so the root cause of sinusitis is often viral, even though, by definition, sinusitis is a bacterial infection of the sinuses.

But only a small fraction of colds — about one in 100 — lead to sinusitis. Some people have chronic sinusitis caused by structural problems that block the ostia, such as a deviated septum or nasal polyps.Acute Respiratory Tract Infection Paper

Prevention. Because sinusitis is often a complication of the common cold, much of the playbook for cold prevention applies. Some doctors recommend regular nasal irrigation, which involves sweeping out the nasal cavities with salted water, but one study showed that regular irrigation may lead to more, not fewer, sinus infections. If you have a cold, don’t blow your nose too hard. Bacteria and mucus can back up into your sinuses if you do.

Treatment. Re-establishing good drainage of the sinuses often eases symptoms and encourages the infection itself to wind down. Drinking lots of water and inhaling steam (try taking extra-long showers) loosens up mucus so the ostia open. Sleeping with your head elevated puts gravity to good use. You can also try one of the oral nasal decongestants. Many doctors want patients to try several days of drainage therapy before prescribing an antibiotic, partly because the antibiotics are more effective if the sinuses are draining, even if just a little. But if the sinusitis is severe to begin with or is not going away, antibiotic therapy is warranted — and usually effective.Acute Respiratory Tract Infection Paper

3. Pharyngitis

What is it? Inflammation of the structures of the pharynx, or back of the throat, which include the back of the tongue, the soft palate (the roof of the mouth), and the tonsils. Strep throat is the form of pharyngitis caused by streptococcus bacteria.

Symptoms. In plain English, pharyngitis is a sore throat. If it’s caused by a viral infection, the symptoms are pain with swallowing, a runny nose, hoarseness, and — in children — diarrhea. If it’s a bacterial infection, the telltale symptoms are a fever and swollen lymph nodes in the neck, usually without a runny nose or cough. Pharyngitis can also be a symptom of other bacterial infections and can occur in diseases that affect more than just the throat, such as mononucleosis and HIV infection.

Causes. By some estimates, 85% of cases are viral. Many of the viruses that cause colds, including rhinoviruses, also cause pharyngitis. In fact, they may cause rhinitis and pharyngitis at the same time. Many types of bacteria cause pharyngitis, but those in the Streptococcal group are the main culprits. The strep bacteria spread through droplets, much like cold viruses, although there are well-documented instances of food-borne outbreaks.Acute Respiratory Tract Infection Paper

Prevention. Cue up that wash-your-hands lecture! And reread the cold-prevention handbook.

Treatment. If it’s viral pharyngitis, the treatment is what doctors call “nonspecific”: rest, pain relievers, salt-water gargles, throat lozenges, and chicken soup, if you like. If it’s strep throat, antibiotics are effective. The trick is making sure it is strep. Symptoms are clues and may suffice, but doctors will often do a rapid, in-office test of a throat swab to be sure of a strep throat diagnosis. The results should be available in minutes. If the test is positive, then treatment is necessary to reduce the (admittedly low) risk of rheumatic fever, a complication of strep throat. If it’s negative, a second test is sometimes done.

4. Bronchitis

What is it? Inflammation of the bronchial tubes that connect the windpipe (trachea) to the lungs. When people talk about having a chest cold, they’re often talking about bronchitis.

Symptoms. A bad cough is the cardinal symptom. It may last for weeks or much longer if the lining of the bronchi remain irritated even after the initial infection has subsided. The cough may be a dry hack, but it may also produce phlegm (sputum), which can be clear, yellow, or green. Wheezing and chest tightness sometimes occur if inflammation has narrowed the bronchi. Some people have bronchitis chronically because of an underlying lung disorder like chronic obstructive pulmonary disease (COPD). An infection can cause chronic bronchitis to flare up and cause more serious symptoms than usual.Acute Respiratory Tract Infection Paper

Causes. Most acute cases — those that come on fairly suddenly — are caused by viral infections that started farther up the respiratory tract and spread down to the bronchi. The bacteria that cause whooping cough (pertussis) can cause acute bronchitis, but bacterial cases of bronchitis are infrequent exceptions to the viral rule. It’s a different story if the bronchitis is a flare-up of COPD: a third to a half of those cases are caused by bacterial infections.


Prevention. Because bronchitis often starts with a cold, the prevention advice is standard-issue. Adults can get a booster shot for whooping cough, and of course, there’s the flu shot for immunizing yourself against the flu.

Treatment. Getting warm, moist air into the bronchi by taking hot showers or using a humidifier can ease the symptoms of acute bronchitis. In some cases, a bronchodilator, the type of inhaled medication used to treat asthma, might help. Most of the time antibiotics should not be prescribed for acute bronchitis because the cause is almost always a viral infection. But if the bronchitis is a flare-up of COPD, then antibiotics are an option.

5. Pneumonia

What is it? An infection and resulting inflammation deep in the lungs, affecting the small air sacs (alveoli) and nearby tissue. “Walking pneumonia” is the term sometimes used for a mild case that doesn’t require hospitalization.Acute Respiratory Tract Infection Paper

Symptoms. The list of symptoms is long and includes fever, chills, cough, and a feeling that you’ve been drained of all energy. If the pleura (the membrane that surrounds the lungs) is affected, then chest pain that worsens when you take a deep breath or cough can be a problem. About 20% of people also have gastrointestinal symptoms such as nausea and diarrhea. Older people may not mount much of a fever, so fatigue and mental confusion might be the most notable symptoms. Oxygen gets into the blood through the alveoli, so bad cases of pneumonia can leave the body short of oxygen. To compensate, breathing may become hurried and labored.

Causes. Most pneumonia is caused by bacteria and Streptococcus pneumoniae bacteria are the most common culprits. About 20% of the pneumonia that occurs outside a health care setting is caused by viruses, including flu viruses. A very small percentage are caused by fungi and other sorts of microorganisms. All of these infectious may be inhaled directly into the lungs, but more commonly, pneumonia starts when viruses or bacteria that have colonized the back of the mouth are drawn into the respiratory tract and down into the lungs. If the bacteria or viruses present are especially infectious, or the natural defense mechanisms of the lungs aren’t functioning well, pneumonia is more likely.Acute Respiratory Tract Infection Paper

Prevention. The pneumococcal vaccine recommended for people over 65 protects against some of the most common types of Streptococcus pneumoniae. A different pneumococcal vaccine is given to children under two. Annual flu shots (and the H1N1 vaccine) not only help prevent pneumonia caused by flu viruses, but bacterial cases that occur secondary to flu infection.

Treatment. A chest x-ray is often necessary to make a definitive diagnosis. Pneumonia is presumed to be caused by a bacterial infection, so most cases are treated with oral antibiotics right off the bat. People at higher risk of complications because of heart disease and other conditions may need to be hospitalized and receive intravenous antibiotics. Usually people start to feel better after several days of antibiotic therapy, but especially in older people, pneumonia can be a life-threatening condition and needs to be watched closely.

Lower respiratory tract infection (LRTI), while often used as a synonym for pneumonia, can also be applied to other types of infection including lung abscess and acute bronchitis. Symptoms include shortness of breath, weakness, fever, coughing and fatigue.

There are a number of symptoms that are characteristic of lower respiratory tract infections. The two most common are bronchitis and edema.[3] Influenza affects both the upper and lower respiratory tracts.

Antibiotics are the first line treatment for pneumonia; however, they are not effective or indicated for parasitic or viral infections. Acute bronchitis typically resolves on its own with time.

In 2015 there were about 291 million cases.[1] These resulted in 2.74 million deaths down from 3.4 million deaths in 1990.[4][2] This was 4.8% of all deaths in 2013.[4]Acute Respiratory Tract Infection Paper

Main article: Bronchitis

Bronchitis describes the swelling or inflammation of the[5] bronchial tubes. Additionally, bronchitis is described as either acute or chronic depending on its presentation and is also further described by the causative agent. Acute bronchitis can be defined as acute bacterial or viral infection of the larger airways in healthy patients with no history of recurrent disease.[3] It affects over 40 adults per 1000 each year and consists of transient inflammation of the major bronchi and trachea.[6] Most often it is caused by viral infection and hence antibiotic therapy is not indicated in incompetent individuals.[7][5] Viral bronchitis can sometimes be treated using antiviral medications depending on the virus causing the infection, and medications such as anti-inflammatory drugs and expectorants can help mitigate the symptoms.[8][5] Treatment of acute bronchitis with antibiotics is common but controversial as their use has only moderate benefit weighted against potential side effects (nausea and vomiting), increased resistance, and cost of treatment in a self-limiting condition.[6][9] Beta2 agonists are sometimes used to relieve the cough associated with acute bronchitis. In a recent systematic review it was found there was no evidence to support their use.[5]

Acute Exacerbations of Chronic Bronchitis (AECB) are frequently due to non-infective causes along with viral ones. 50% of patients are colonised with Haemophilus influenzae, Streptococcus pneumoniae or Moraxella catarrhalis.[3] Antibiotics have only been shown to be effective if all three of the following symptoms are present: increased dyspnea, increased sputum volume and purulence. In these cases 500 mg of Amoxycillin orally, every 8 hours for 5 days or 100 mg doxycycline orally for 5 days should be used.[3]

Most people have heard the term upper respiratory infection. It is often used interchangeably when describing a respiratory virus or the common cold. But do you know what a lower respiratory infection is?

Lower respiratory infections are illnesses that affect the respiratory system below the throat. Any infection that affects the lungs and lower airways are considered a lower respiratory infection.

The most common and well-known lower respiratory infections are pneumonia and bronchitis, as well as bronchiolitis in children.Acute Respiratory Tract Infection Paper


Pneumonia is an infection of the lungs. There are many types of pneumonia. It can be caused by different types of bacteria, viruses, fungi and even inhaled chemicals or solid objects (such as food). Many cases of pneumonia occur as a complication of an upper respiratory infection such as a cold or the flu.

Most of the time, people with pneumonia are treated with antibiotics. Other medications may be necessary to help with the symptoms. If your illness is severe or you are at high risk, you may be hospitalized when you have pneumonia. To help reduce your risk of serious illness, get your flu vaccine each year. Older adults should get a pneumonia vaccine as well.


Bronchitis is irritation and swelling of the airways leading to the lungs. Most often, it is caused by a virus and will go away on its own. Although coughing can be uncomfortable and last for weeks, antibiotics are rarely helpful for bronchitis since they do not kill viruses. Other treatments may be useful if you have been diagnosed with bronchitis. Your healthcare provider may prescribe an inhaler to help with a cough and breathing difficulty. She may also recommend over the counter medications such as pain relievers or expectorants.

If you have bronchitis but start to feel worse and run a fever, contact your healthcare provider or seek medical attention. Sometimes secondary bacterial infections develop in people with bronchitis. If this happens, your treatment will be different and antibiotics may be necessary.


Bronchiolitis is inflammation or swelling of the small airways in the lungs. It is an illness that occurs primarily in children younger than 2 years old. It most commonly occurs in babies between 3 and 6 months old, with RSV being the primary cause.

Wheezing and coughing are the primary symptoms of bronchiolitis. It can be a serious and sometimes fatal illness for young infants. If you notice any of these signs that your child is having difficulty breathing, seek medical attention right away, even if you don’t suspect bronchiolitis. It’s important to know what to watch for. It’s not always obvious when a child is having trouble breathing. Knowing what to watch for could save a child’s life. Acute Respiratory Tract Infection Paper

Lower respiratory infections can be dangerous and generally are more serious than upper respiratory infections. Know what to watch for so you can seek medical attention if it’s needed.

Upper respiratory infections are more common during the fall and winter. This may be due colder weather and lower humidity levels. Viruses are more active during these times of low humidity. People are also more susceptible during these types of weather conditions. The best course of prevention is to wash your hands frequently and get your flu shot. This is by no means a fail safe. If you are experiencing an upper respiratory infection, the best treatment is to stay hydrated and get plenty of rest.

The term upper respiratory infection refers to an infection of your upper respiratory tract. This includes your nasal passages, sinuses, and upper airways. The symptoms are usually short lived. The typical length of infection is around fourteen days. This is because the main cause of upper respiratory infections is viral in nature. However, prolonged illness may be cause to seek medical attention. Secondary infections caused by bacteria can lead to a more protracted illness of greater than two weeks. Children and the elderly are also at greater risk for complications. Medical intervention may become necessary for these groups of people. Here are some of the signs and symptoms that you may experience during an upper respiratory infection.Acute Respiratory Tract Infection Paper

1. Nasal Congestion

The first few days of an upper respiratory infection generally involve nasal congestion. You may have an overall stuffy feeling or it can be more painful. Swelling in the nasal passages causes this stuffy feeling. Your sinuses are irritated by the infection. This can lead to trouble breathing. You can use a nasal strip in order to open up the nasal passages. This may help you to get some much needed rest. Congestion that is painful is due to the buildup of mucus in the sinus cavities. This condition can typically be relieved by using a decongestant.

It isn’t recommended to give young children cold medication. There are natural remedies that you can try for your kids. You can use a humidifier to help with reducing this congestion. Other solutions are to clear out the sinuses with a saline spray. It may even be helpful to sleep propped up on a pillow. This may relieve some of the discomfit associated with nasal congestion. For severe pain, using a pain reliever may be beneficial for kids. This congestion can be brief or may last a few days before the sinuses start to release the mucus. This leads into the next sign of an upper respiratory infection.Acute Respiratory Tract Infection Paper

Inappropriate use of antibiotics is contributing to the increasing rates of antimicrobial resistance. Several Danish guidelines on antibiotic prescribing for acute respiratory tract infections in general practice have been issued to promote rational prescribing of antibiotics, however it is unclear if these recommendations are followed. We aimed to characterize the pattern of antibiotic prescriptions for patients diagnosed with acute respiratory tract infections, by means of electronic prescriptions, labeled with clinical indications, from Danish general practice. Acute respiratory tract infections accounted for 456,532 antibiotic prescriptions issued between July 2012 and June 2013. Pneumonia was the most common indication with 178,354 prescriptions (39%), followed by acute tonsillitis (21%) and acute otitis media (19%). In total, penicillin V accounted for 58% of all prescriptions, followed by macrolides (18%) and amoxicillin (15%). The use of second-line agents increased with age for all indications, and comprised more than 40% of the prescriptions in patients aged >75 years. Women were more often prescribed antibiotics regardless of clinical indication. This is the first Danish study to characterize antibiotic prescription patterns for acute respiratory tract infections by data linkage of clinical indications. The findings confirm that penicillin V is the most commonly prescribed antibiotic agent for treatment of patients with an acute respiratory tract infection in Danish general practice. However, second-line agents like macrolides and amoxicillin with or without clavulanic acid are overused. Strategies to improve the quality of antibiotic prescribing especially for pneumonia, acute otitis media and acute rhinosinusitis are warranted.Acute Respiratory Tract Infection Paper


Antimicrobial resistance rates have reached alarming levels and presently constitute a serious public health concern by threatening one of the most effective and mortality lowering interventions in modern medicine.1 Part of the solution to this problem includes minimizing overuse of antibiotics as they are directly linked to the development of antimicrobial resistance.2 As a consequence, it is imperative we make judicious use of the available antibiotics in order to maintain their effectiveness in the years ahead.

Acute respiratory tract infections are common reasons for consulting in general practice and assumed responsible for more than 60% of the antibiotic use in this setting.3 But the effect of antibiotic treatment, when pneumonia is not suspected, is at best moderate,4,5,6 indicating that a large amount of antibiotic prescriptions are in fact inappropriate and confer no net benefit for the patient. Strategies, such as guidelines on rational antibiotic use, as well as educational and decision support systems are applied to improve antibiotic prescribing. However, the implementation of these strategies into daily clinical routine can be difficult and daily practice is far from optimal7, 8 in turn augmenting the risk of inappropriate prescribing both in regard to quantity (e.g., over prescribing) and quality (e.g., non-optimal choice of antibiotic).9Acute Respiratory Tract Infection Paper


As antibiotic resistance rates are low in Denmark10 National Guidelines11 on antibiotic prescribing for acute respiratory tract infections recommend narrow-spectrum penicillin (penicillin V) as first-line agent for acute respiratory infections, except acute exacerbation’s of chronic obstructive pulmonary disease (AECOPD) where the recommendation was amoxicillin with clavulanic acid (co-amoxicillin).

In Denmark, previous attempts to assess current prescribing practice for specific infections have been based on small subsets of general practitioners that volunteered to participate for a limited time.12

Surveillance of antibiotic prescribing and consumption is a central element in containing the increasing antimicrobial resistance.9, 13 Patterns of antibiotic prescriptions, particularly when linked to clinical indications and patient demographics, can be helpful in determining appropriateness of the issued prescribing: lately results from the UK and the Netherlands have successfully applied data linkage to characterize prescribing of flucloxacillin and analyze trends in prescribing for sore throat, colds, and acute cough.14,15,16

To promote rational antibiotic use in Denmark, and study the link between clinical indications and the associated antibiotic prescribing, an electronic system with mandatory data entry of clinical indications for antibiotic prescribing was introduced in 2011.Acute Respiratory Tract Infection Paper

We aimed to characterize the pattern of antibiotic prescriptions for acute respiratory tract infections, by means of clinical indications from electronic prescriptions, in regard to national guidelines on antibiotic prescribing in Danish general practice.

Antibiotics transformed medical practice in the last half of the 20th century. Penicillin was even called a miracle drug by many in the 1950s and 1960s. Since that time, however, there has been increasing awareness that treating non-bacterial illnesses or those that are self-limiting with antibiotics contributes to the development of antibiotic-resistant bacteria.1,2 Reducing inappropriate antibiotic use is critical to slowing the progression of these resistant bacteria. Furthermore, inappropriate antibiotic use exposes patients unnecessarily to potential side effects associated with antibiotics and increases medical costs.

Acute respiratory tract infections (RTIs) account for approximately 70 percent of primary diagnoses in adults presenting for an ambulatory office visit with a chief symptom of cough.3 Acute RTIs include acute bronchitis, otitis media, pharyngitis/tonsillitis, rhinitis, sinusitis, and other viral syndromes4 Standard management of acute RTIs is to focus on ruling out serious illness in which antibiotics are indicated, such as bacterial pneumonia, and provide education and symptomatic relief for illnesses that do not require antibiotics. Existing clinical guidelines indicate that acute bronchitis and other acute RTIs that can be caused by viral or bacterial infections and are generally self-limiting should generally not be treated with antibiotics unless certain clinical indications are present.4 Despite guidelines recommending no antibiotic treatment for most acute RTIs, the majority of outpatient antibiotic prescriptions in the US are for acute RTIs. In 1998, an estimated 76 million ambulatory office visits for acute RTIs resulted in 41 million antibiotic prescriptions.5 A 2013 report of healthy adults visiting outpatient offices and emergency departments for acute bronchitis revealed prescriptions for antibiotics were given at 73 percent of visits between 1996 and 2010,6 despite the fact that the majority of acute bronchitis cases are caused by viral pathogens for which antibiotics are not helpful. Therefore strategies that can help bring antibiotic use for RTIs in line with current evidence-based guidelines are clearly needed.Acute Respiratory Tract Infection Paper

Interventions for improving appropriate use of antibiotics for RTI

Strategies to improve appropriate use of antibiotics for RTIs vary by both whose behavior they are trying to influence and how they are seeking to change that behavior. Strategies may target clinicians and others who care for patients with acute RTI in outpatient settings, adult and pediatric patients with acute RTI, the parents of pediatric patients with acute RTI, healthy adults and/or children without a current acute RTI, or groups whose attendance policies may indirectly affect the use of antibiotics (e.g., employers, school officials). Interventions may also fall into one of several categories. Educational strategies include educating clinicians about current treatment guidelines or providing information to patients or parents of patients about why antibiotic treatment is not recommended. Strategies to improve communication between clinicians and patients include interventions designed to improve shared decision making. Clinical strategies include delayed prescribing of antibiotics or use of point-of-care diagnostic tests (e.g., rapid strep). System level strategies include clinician reminders (paper-based or electronic), clinician audit and feedback, and financial or regulatory incentives for clinicians or patients. Furthermore, multifaceted approaches may include numerous elements of one or more of the strategies.Acute Respiratory Tract Infection Paper

Relevant outcomes

The increasing prevalence of antibiotic resistant microorganisms is the principal public health concern motivating efforts to improve appropriate antibiotic prescriptions and use. Additionally, improved appropriate antibiotic use is expected to have other benefits, particularly a reduction in adverse drug events related to antibiotics. These are the most important health outcomes of interest in evaluating interventions to improve appropriate antibiotic use. However, because these outcomes can be difficult to measure directly, other outcomes that occur intermediately between the intervention and the health outcome are also important in evaluating the impact of such interventions. For example, antibiotic resistance may be affected by factors other than inappropriate prescribing of antibiotics for acute RTI. The most commonly reported outcome is likely to be the rate of appropriate antibiotic prescription. While this is the most direct outcome of interventions intended to improve appropriate prescription, there is not always consensus on how appropriateness is defined and measured. Therefore it will be important to capture how each study defines and measures appropriateness and consider this heterogeneity in the analysis. Other relevant intermediate outcomes include improved knowledge regarding use of antibiotics for acute RTI and improved shared decision making by patients and clinicians. These outcomes have a weak link to health outcomes, including antibiotic resistance than other intermediate outcomes.

There are also potential negative effects from these interventions. Because individual clinical assessments of the need for antibiotics are not always accurate, a variety of other desirable and undesirable outcomes might be affected by efforts to improve appropriate antibiotic use. For example, if efforts to improve appropriate antibiotic use resulted in under-treatment of patients for whom antibiotics would have been indicated, undesirable outcomes such as medical complications, hospital admissions, and mortality might increase. Similarly, reduced prescription of antibiotics may lead to increased clinic visits, longer duration of symptoms, or longer time to return to school or work. Depending on patients’ expectations, patient satisfaction may also be affected. The interventions themselves also may require substantial time and resources. Therefore, a systematic review of interventions to improve appropriate antibiotic use should also include those outcomes.Acute Respiratory Tract Infection Paper

Existing guidance

Existing guidelines recommend the use of various interventions to improve appropriate antibiotic prescription by physicians and reduce the use of antibiotics by patients. A 2008 guideline by the United Kingdom’s National Institute for Health and Clinical Excellence (NICE), entitled “Respiratory tract infections- antibiotic prescribing,” recommends delayed antibiotic prescribing and patient education about the expected duration of RTI symptoms.4 As a strategy to improve appropriate antibiotic use in children, the US Centers for Disease Control and Prevention (CDC) recommends that clinicians educate parents about the ineffectiveness of treating most upper respiratory infections with antibiotics and planning for treatment of symptoms7 The Michigan Quality Improvement Consortium suggests similar strategies, and recommends using the term “chest cold” with patients to describe an acute respiratory infection, as this less technical term is thought to sound more commonplace and less likely to require antibiotics.8 Each of these guidelines is limited – in its scope, in its evidence base, or in its assessment of the comparative effectiveness of different strategies in different patients under different circumstances. For example, the Michigan Quality Improvement Consortium guidelines are based on evidence limited to acute bronchitis. And, the 2008 NICE guideline report recognizes its limited conclusions with recommendations for needed future research into questions of comparative effectiveness of interventions and subgroup differences. Finally, the evidence upon which these guidelines are based is not current.

Availability of scientific data and rationale for an evidence review

Inappropriate prescribing and use of antibiotics for acute RTIs is a common and serious public health problem. Therefore, it is important to understand the comparative effectiveness of strategies for reducing inappropriate antibiotic use. Previous systematic reviews and existing guidelines are lacking in a variety of ways that limit their usefulness for addressing the key questions proposed for the current topic. Notably, these reviews have not assessed the actual comparative effectiveness of various strategies. The most comprehensive review to date, a 2006 technical review by AHRQ, entitled “Closing the Quality Gap: A Critical Analysis of Quality Improvement Strategies Volume 4—Antibiotic Prescribing Behavior.” included evidence about inappropriate use of antibiotics when none are indicated, as well as use of the incorrect antibiotic when one is indicated.Acute Respiratory Tract Infection Paper The report concluded that some quality improvement strategies may be moderately effective in reducing inappropriate antibiotic prescription; that no single strategy is clearly superior, but clinician education and delayed prescribing may be more effective in certain settings; and that interventions targeting prescribing for all acute RTIs may be more effective than those that target a single type of RTI. While the 2006 AHRQ review was not limited to RTIs, it appears to adequately address the literature related to RTIs.However, the 2006 AHRQ review, is out of date. Our literature scan identified three additional systematic reviews of strategies designed specifically to improve appropriate antibiotic use for acute RTI. One of those reviews, from 2004, was limited to a single strategy (delayed prescribing), and was not cited in the 2006 AHRQ technical review.9 The other two systematic reviews were published in 2012 and 2013.10,11 Both of these latter two reviews were limited to pediatric patients; one was further limited to interventions targeting parents or caregivers10 and the other was limited to interventions directly targeting clinicians and/or parents.11 These reviews leave gaps in knowledge about interventions aimed at adult populations, other types of interventions or outcomes., We find that there are a sufficient number of studies published since these reviews were conducted that conclusions may be altered; in addition to the trials summarized in these reviews, through a preliminary literature search we found 11 randomized controlled trials and 10 nonrandomized studies of strategies to improve appropriate antibiotic use for acute RTI published since the 2006 AHRQ report. For these reasons, the proposed systematic evidence review would be valuable for assessing the comparative effectiveness of a breadth of possible strategies for reducing antibiotic use when not indicated for acute RTIs in adults and children.

The Key Questions

The topic was nominated by a diverse group of stakeholders, including patients, clinicians, professional societies, and insurers through an AHRIMAN-sponsored topic identification exercise. Topic refinement was undertaken by the Pacific Northwest Evidence-based Practice Center (PNW EPC), including consultation with a group of Key Informants and AHRQ representatives. AHRQ posted the revised key questions on the Effective Health Care Website for public comment.Acute Respiratory Tract Infection Paper The comments received addressed the definition of appropriate use of antibiotics for acute RTI, inclusion of patients in institutional settings, framing of key questions as applying to patients versus a broader population (e.g. the general public, or targeted healthy groups), inclusion of patients with cough as the primary symptom of acute RTI, further delineation of interventions and intervention characteristics to be considered, inclusion of some point-of-care diagnostic tests, further delineation of outcomes and outcome characteristics to be included, consideration of the need to compare settings (e.g. primary care and emergency care), and improvements to the analytic framework. The key questions and inclusion criteria were modified based on these comments, and comments from the key informants and AHRQ representatives. Changes included:


Stipulating that institutional settings will be included under outpatient settings
Expanding the interventions list to include point-of-care diagnostic tests and interventions that work through behavioral or psychological mechanisms
Adding patient-centered communication that is appropriate for culture and level of health literacy to the outcomes for KQ3
Adding frailty and comorbidity as examples of important factors in the prior medical history to be considered in KQ 1b
Adding physical signs as part of the patient characteristics considered under KQ1b, to reflect elements of a physical exam relevant to diagnosis of acute RTI
Definitions and methods for determining appropriate versus inappropriate use of antibiotics in Acute RTI will be recorded as reported in each study, including where one or both are not reported. We will undertake analysis of the results based on variation in these variables to assess their potential impact on outcomes.Acute Respiratory Tract Infection Paper

The PNW EPC solicited additional input from the Technical Expert Panel (TEP). Refinements of note based on TEP input include:

Reframed focus from reducing inappropriate use to improving appropriate use
Further clarified approach to handling variation in appropriateness definitions
Population: Removed list of indications for antibiotic treatment
Interventions: Broadened list to include additional point of care tests (e.g. procalcitonin, c-reactive protein (CRP), , rapid multiplex polymerase chain reaction (PCR) tests -influenza, rapid strep, RSV (-, white blood cell, chest x-ray, pulse oximetry, blood gasses), clinical prediction rules, antimicrobial stewardship programs, risk assessment/prognostic diagnosis, and pharmacist review
Outcomes: ED visits, all clinic visits (including for index, return and subsequent episodes), clostridium difficile infections, sustainability, diagnostic coding according to desired action, improvement in patient symptoms, speed of improvement, utilization of vaccinations, quality of life
Key sources of variation: When counting began for duration of signs and symptoms, previous RTIs, the diagnostic method or definition used, the clinician’s perception of the patient’s illness severity, or the clinician’s diagnostic certainty, source of resistance data (population versus study sample)

Antibiotic overuse for ARTIs is common worldwide and is associated with unnecessary healthcare costs, increased adverse drug effects, and the growing global threat of antibiotic resistance. In low- or middle-income settings, antibiotic overuse for ARTIs can be even more pronounced due to factors such as limited access to laboratory testing. In southern Sri Lanka, we were able to document influenza seasonality over a 2-year period using a newer-generation rapid influenza test. Further comprehensive testing for ARTI etiology using a test that detects a broad panel of respiratory viruses is currently underway. In our study, the majority of patients (>80%) with ARTIs received antibiotic prescriptions, with most of these likely being unnecessary. Providing clinicians with access to positive rapid influenza test results was associated with a significant drop in antibiotic prescriptions. We are currently in the process of conductive a qualitative assessment of rapid diagnostic uptake and antibiotic prescribing practices, as well as a cost effectiveness assessment of rapid influenza testing. The ultimate goal is to leverage diagnostics to improve antibiotic stewardship for ARTIs in low- or middle-income settings.Acute Respiratory Tract Infection Paper

Appropriate prescribing of antibiotics for patients with respiratory tract infections (RTI) is a key component of improving antimicrobial stewardship in New Zealand. Most respiratory tract infections, particularly those affecting the upper respiratory tract, are viral in origin and self-limiting. Antibiotic treatment should ideally be reserved for specific subsets of patients with bacterial respiratory tract infections such as community acquired pneumonia, or used if the potential for complications for that person are high or if the infection is not resolving within an expected timeframe.

It would be assumed, therefore, that the management of people presenting with respiratory tract infections is relatively straight forward and the decision not to prescribe an antibiotic an easy one to make. However, every day, and often several times a day, primary care clinicians see a range of people with symptoms that are consistent with a number of possible respiratory tract infections, and many factors can influence their decision about whether or not to prescribe an antibiotic. It has been reported that approximately 60% of all antibiotic prescribing in primary care in the United Kingdom is for patients with respiratory tract symptoms,1 and although there are no similar New Zealand figures, it is likely that comparable prescribing trends occur here.Acute Respiratory Tract Infection Paper

Both clinical and non-clinical factors can influence treatment decisions for patients with respiratory tract infections. The initial clinical evaluation, i.e. history and examination, can provide information about the probable cause of the patient’s symptoms but it is often difficult to distinguish clinically between viral and bacterial infections. A fear of not “missing” the diagnosis of a significant bacterial infection may mean that if there is clinical uncertainty, clinicians err on the side of caution and prescribe. This may be an appropriate response, particularly if the risk of not doing so is high, e.g. non-specific respiratory symptoms and signs in a patient who is suppressed. In other situations, clinical guidance may recommend that an empiric antibiotic is appropriate, e.g. a child with a sore throat who has risk factors for rheumatic fever, or a student who has symptoms and signs that may suggest meningitis.

Non-clinical factors can also complicate management decisions. Often there is expectation and pressure from the patient for an antibiotic because they perceive that it will improve their symptoms – sometimes the clinician will assume that the patient wants an antibiotic. Other factors that may impact prescribing decisions include: the day of the week (the “Friday afternoon consultation”), important life events (“I’m flying tomorrow”, “I have a major examination/singing competition”), and previous experiences affecting either the clinician or the patient, particularly any that have had bad outcomes.Acute Respiratory Tract Infection Paper

Whatever decision is made, a key factor is to effectively communicate the reasons for this decision to the patient, and to provide advice about non-antibiotic strategies for the patient to manage their symptoms. Good clinician-patient communication has been shown to reduce the rates of antibiotic prescribing for respiratory tract infections both at the initial consultation and during future consultations.2

To try to shed some light on what actually happens in consulting rooms around the country, we asked a number of health professionals for their thoughts and opinions on their approach to the management of people with respiratory tract infections.

Q: What key clinical and non-clinical factors do you take into account in the initial assessment of a patient with a respiratory tract infection and when deciding if a patient needs an antibiotic?

Duration, severity and progression of symptoms appear to be the key factors for primary care clinicians when deciding whether a patient with a RTI requires an antibiotic. Important signs on examination include chest sounds, temperature, respiratory rate and hydration status, along with characteristics of cough if present, and whether the patient appears systematically unwell. Other clinical factors which are taken into consideration include co-morbidity (e.g. if the patient has COPD), immune status and previous history of complications with a RTI.Acute Respiratory Tract Infection Paper

The most frequently cited non-clinical factors which affect the decision to prescribe an antibiotic were the patient’s living and social circumstances, including whether there are other vulnerable people present in the household, and the patient’s ability to re-consult or access after-hours services if required. Important life events and patients concerns and expectations also factor into the decision to prescribe antibiotics for some clinicians.

For a patient to need an antibiotic (rather than want or request one) I would need to have a bacterial diagnosis, such as pneumonia, or enough symptoms and delay to consider sinusitis or otitis media. I don’t think there is such a thing as a secondary bacterial infection. Coloured sputum is not an indication for an antibiotic unless there are other signs and symptoms that make one think of pneumonia. A sick looking patient may make me err on the side of giving an antibiotic but then I should be thinking of admitting the patient.

What diagnostic tests, if any, would you perform and why?

There was general agreement that laboratory investigations are not routinely required for patients presenting with a non-complicated RTI. The exception to this was taking a throat swab in a patient presenting with a sore throat, with risk factors for rheumatic fever. If a patient was very unwell, if they had persistent symptoms or if there were significant concerns, investigations may include full blood count, CRP, referral for chest x-ray if indicated and occasionally sputum culture if cough is persistent.Acute Respiratory Tract Infection Paper

Q: How do you manage patient expectations about antibiotics?

Every upper RTI is an opportunity for education and re-enforcing key messages [about antibiotics].

There is no standard approach to managing expectations, as patients have a variety of beliefs about antibiotics, ranging from those who have come from countries where receiving an antibiotic is standard to those who are concerned that taking an antibiotic will affect their immunity. It is a useful approach to ask the patient about their expectations regarding antibiotics early in the consultation.

Clinicians felt that it was important to explain the following key messages about antibiotics to patients:

The majority of RTIs are viral and self-limiting and do not require antibiotic treatment
Antibiotics usually do not alter the course of illness in a non-complicated RTI
The over-prescribing of antibiotics contributes to antibiotic resistance, which means that antibiotics might not work when they are needed, which is not only bad for the individual but also for the community as a whole
Antibiotics are associated with adverse effects, e.g. diarrhea, nausea, and in rare cases more serious outcomes such as allergic reaction
Being prescribed an antibiotic in the past for a RTI does not necessarily mean that one is required in this case

Patient leaflets were thought to be useful in managing patient expectations, improving health literacy and complementing a verbal discussion to help patients understand why an antibiotic is not required for a RTI.Acute Respiratory Tract Infection Paper

Respiratory tract infections (RTIs) remain the commonest reason for acute consultations in primary care in resource-rich countries. Their spectrum and severity has changed from the time that antibiotics were discovered, largely from improvements in the socioeconomic determinants of health as well as vaccination. The benefits from antibiotic treatment for common RTIs have been shown to be largely overstated. Nevertheless, serious infections do occur. Currently, no clinical features or diagnostic test, alone or in combination, adequately determine diagnosis, aetiology, prognosis, or response to treatment. This narrative review focuses on emerging evidence aimed at helping clinicians reduce and manage uncertainty in treating RTIs. Consultation rate and prescribing rate trends are described, evidence of increasing rates of complications are discussed, and studies and the association with antibiotic prescribing are examined. Methods of improving diagnosis and identifying those patients who are at increased risk of complications from RTIs, using clinical scoring systems, bio markers, and point of care tests are also discussed. The evidence for alternative management options for RTIs are summarized and the methods for changing public and clinician’s beliefs about antibiotics, including ways in which we can improve clinician–patient communication skills for management of RTIs, are described.

Respiratory tract infections (RTIs) remain the commonest reason for acute consultations in primary care in resource-rich countries. Their spectrum and severity have changed from the time that antibiotics were discovered, when the mortality rate from pneumococcal pneumonia was over 20% (rising to 60% with associated bacterial).1 Penicillin was considered a ‘wonder drug’ at that time, and antibiotic treatment gradually became the norm even for mild respiratory infections. However, the decline in morbidity and mortality from infectious diseases in the 20th century flowed largely from improvements in the socioeconomic determinants of health (such as, basic hygiene and sanitation), as well as vaccination, and the benefits from antibiotic treatment for common RTIs has been shown to have been largely overstated.2 Nevertheless, serious infections that might be prevented by early antibiotic treatment still occur. Therefore, while these consultations are often considered the ‘bread and butter’ of general practice, they are made challenging by the need to manage diagnostic and prognostic uncertainty. No clinical features or current diagnostic test, alone or in combination, adequately determine diagnosis, aetiology, prognosis, or response to treatment. This narrative review focuses on emerging evidence aimed at helping clinicians reduce and manage uncertainty in treating RTIs. Medline was searched using the following terms: respiratory tract infections, diagnosis, prognosis, and management for relevant references, and The Cochrane Database Acute Respiratory Infections Group was searched for relevant systematic reviews.Acute Respiratory Tract Infection Paper

Antibiotic prescribing

Antibiotic prescribing in primary care steadily increased in developed countries up until the 1990s when it leveled off and then declined by about a third.3,4 However, despite robust evidence from observational studies and randomized controlled trials highlighting little or no benefit from antibiotic treatment for most people presenting with RTI symptoms, these illnesses are still the commonest reason for antibiotic prescribing in primary care,5 and prescribing rates have now stopped declining and may be increasing again.4

Antibiotic prescribing puts individuals at risk from side effects, encourages help-seeking behaviour for (mainly) self-limiting illnesses, and puts both individuals and society at risk from increasing antibiotic resistance.6 Many GPs do not link their own prescribing practices with increasing antibiotic resistance and regard resistance as essentially a hospital-based problem.7 There is wide variation in antibiotic prescribing across Europe,8–10 and within the UK,11 with no evidence that this is associated with differing disease spectrum or complication rates.8

The 2008 National Institute for Clinical Excellence (NICE) guidelines recommend no antibiotics or delayed antibiotics for most patients with RTI (Box 1).12

How this fits in

Respiratory tract infections are common and most benefit very little if at all from antibiotic treatment. Differentiating the few patients at higher risk from a complicated course from the majority who will recover uneventfully remains a challenge, and antibiotics continue to be widely overused. Clinical prediction rules, identification of ‘at risk groups, near-patient tests, and better communication regarding uncertainty (such as use of shared decision making, interactive booklets, and delayed prescribing) can all help target antibiotics to those most likely to benefit. Public health campaigns, reinforcing basic hygiene messages, and vaccination for at-risk groups also improve outcomes and reduce inappropriate antibiotics.Acute Respiratory Tract Infection Paper

In total, community-acquired respiratory tract infections (CARTIs) account for more than 116 million annual office visits, making them the most common condition for which antibiotics are prescribed in the United States1,2 and representing a large burden on clinicians’ time. This burden is further complicated by the uncertainty surrounding these infections; when patients initially present with a suspected CARTI, the origin of the illness (viral or bacterial) must first be evaluated. Once a bacterial infection is suspected, the decision for antimicrobial therapy is typically empirical, with agent selection influenced by local bacterial susceptibility and previous experience.3


Respiratory tract infections (RTIs) are responsible for 50 million deaths globally each year.3 The most frequently occurring CARTIs in the United States are acute rhinosinusitis (AS), acute exacerbations of chronic bronchitis (AECB), and community-acquired pneumonia (CAP).4 These conditions, specifically CAP and AECB, are associated with significant morbidity and mortality rates.3
AS can be described as a bacterial infection of the paranasal sinuses lasting less than 30 days, in which symptoms resolve completely. There are 31 million cases of AS annually,5 making it the fifth most common diagnosis for which antibiotics are prescribed.6 In total, this condition accounts for 73 million restricted activity days per year.5
Chronic bronchitis is usually defined as a condition characterized by cough and sputum production on most days for a prolonged period of time recurring each year. AECB, an acute exacerbation of this long-term process, is characterized by increased cough, sputum production, and dyspnea, in addition to development of sputum purulence. AECB should not be confused with acute bronchitis, which is a viral infection caused by environmental conditions. There are about 32 million cases of AECB annually among 11 million people,7,8 resulting in 1.5 million emergency hospital visits and 500 000 hospitalizations per year.9 Ninety percent of these cases are patients who are current or former smokers.10
Pneumonia is an infection of the lung parenchyma. CAP refers to pneumonia acquired outside of hospitals or extended-care facilities. More than 5 million cases of CAP occur annually, resulting in 10 million office visits, 1.1 million hospitalizations, and more than 45 000 deaths.3,11,12 CAP is associated with a significant overall mortality rate of >8%, making it the most common cause of death from infection.13 When focusing specifically on hospitalized patients, the mortality rate ranges from 8.5% to 15.8%,13-17 and when limited to the patients in the intensive care unit (ICU), the mortality rate is as high as 36.5%.17
Causative Pathogens. Typically, there are 3 pathogens that account for the majority of CARTIs: Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.18-20 Further, a group of atypical pathogens (Legionella spp, Mycoplasma pneumoniae, and Chlamydophila pneumoniae) account for significant morbidity and mortality rates in CAP. The specific percentages of these pathogens responsible for CARTIs are listed in the Table.Acute Respiratory Tract Infection Paper
Antimicrobial Resistance. Empiric management of CARTIs has been challenged by the emergence of resistance to typical respiratory pathogens. In the 1980s, antimicrobial-resistant S pneumoniae became widespread in many parts of the world.21 In the United States, however, resistance did not become a significant problem until the 1990s. It is estimated that 34% of S pneumoniae isolates are resistant to penicillin,21 20% to 30% are resistant to macrolide therapy,22 and 35% are resistant to trimethoprim-sulfamethoxazole.21 In fact, of the penicillin-resistant S pneumoniae isolates, 78% were multidrug resistant.23
During the 1980s, penicillin resistance rates in the United States were at levels of 3% to 5%24,25; however, these rates jumped to 17.8% by 1991 to 1992.26 Ongoing surveillance studies clearly show that the problem of penicillin-resistant S pneumoniae has steadily risen from the early 1990s to reach the level of 34% resistant for the period of 1999-2000.21 Although penicillin-resistant S pneumoniae was identified as early as 1974,27 macrolide-resistant S pneumoniae emerged at a later date. In 2000, a national, longitudinal, multicenter surveillance study was initiated to track the emergence and spread of resistance among CARTI pathogens.23 In this study, data collected from more than 200 medical centers confirmed the widespread prevalence of erythromycin resistance (minimum inhibitory concentration [MIC] ≥1 mg/L) to S pneumoniae across the United States. The resistance rates collected varied across geographic regions, ranging from 40.2% in the Southeast to 23.2% in the Northwest.23 The continuing spread of resistance in typical respiratory pathogens reaffirms the importance of continued surveillance to guide optimum empiric therapy for patients with CARTIs.


Appropriate Management of CARTIs
The leading factor contributing to the increase in resistance is the inappropriate use of antibiotics. Although most of this inappropriate use stems from an inability to quickly and unequivocally determine the etiology of infection (viral vs bacterial), patient history and signs and symptoms of disease may provide insight into which patients have a high likelihood of bacterial infection. Once the decision has been made to initiate therapy, 2 factors should be taken into consideration when selecting an antibiotic for the treatment of CARTIs. The first factor is an agent’s spectrum of activity. When treating CARTIs, the use of an antibiotic with a tailored spectrum of activity should ensure coverage of typical pathogens, resistant strains, and atypical pathogens, without coverage of nonrespiratory, gram-negative pathogens. The second factor is selecting an agent with a low potential to induce future antibiotic resistance. When treating CARTIs, the use of an antibiotic with chemical properties that may minimize the risk of developing resistance should be considered. Properties affecting resistance include potency, half-life, bactericidal activity, and binding affinity at multiple sites. Together, these 2 factors form the basis of a useful framework to select antibiotic agents for the treatment of CARTIs.Acute Respiratory Tract Infection Paper
Spectrum of Activity. As previously discussed, the causative pathogens for CARTIs include S pneumoniae, H influenzae, and M catarrhalis, resistant pathogens, and atypical pathogens. When selecting antibiotic therapy for CARTIs, the clinician should select a product that not only covers these pathogens, but also has limited or no effect on nonrespiratory, gram-negative pathogens. This is the concept of a tailored spectrum.
The primary focus of empiric therapy for CARTIs relies on coverage of infections caused by typical respiratory pathogens: S pneumoniae, H influenzae, and M catarrhalis. A number of antibiotics available today meet this requirement, including beta-lactams, fluoroquinolones, ketolides, and macrolides. Yet coverage of these susceptible pathogens is not enough to guarantee adequate treatment of these infections.
Although not the leading cause of CARTIs, atypical pathogens may account for up to 20% of CAP cases.28 These pathogens often go undetected because of the infrequent use of diagnostic tests. This factor underlies the recommendations in the Infectious Diseases Society of America, American Thoracic Society, and the American College of Clinical Pharmacy treatment guidelines to include empiric coverage of atypical pathogens when treating CAP.29-31 These pathogens are covered by a number of antibiotics available today, including the fluoroquinolones, ketolides, and macrolides. The beta-lactam antibiotics do not provide coverage of atypical pathogens.Acute Respiratory Tract Infection Paper
In addition to covering typical and atypical pathogens, the selected agent should be able to combat infections from resistant forms of typical respiratory pathogens. Resistant forms of S pneumoniae have increasingly become a public health problem. As stated, rates of penicillin-resistant S pneumoniae and macrolide-resistant S pneumoniae have rapidly increased over the past decade, and this increasing resistance has adversely influenced clinical outcomes. Two studies demonstrating this impact are described below.
A study by Einarsson and colleagues demonstrated the difference in clinical outcomes of patients with pneumonia caused by penicillin-nonsusceptible pneumococci (PNSP) and penicillin-susceptible pneumococci (PSP). Patients with PNSP pneumonia had a significantly longer hospital stay (26.8 vs 11.5 days; P = .001) and a higher average cost of antibiotics ($736 vs $213; P <.0001) compared with those with PSP pneumonia.32 A study examining the epidemiologic factors affecting mortality from pneumococcal pneumonia included patients residing in a surveillance area with CAP who required hospitalization. Increased mortality was associated with a number of factors including age, underlying disease, Asian race, and residence. When these factors were controlled for and deaths during the first 4 hospital days were excluded, mortality was significantly associated with a penicillin MIC of 4.0 or higher.33 A number of studies have reported macrolide failures in the treatment of RTIs. This growing body of evidence suggests that macrolide failure is an increasing clinical problem.34-41 One study, examining the development of breakthrough bacteremia during macrolide treatment of pneumococcal infection and its relationship to the macrolide susceptibility of the pneumococcal isolate, identified 86 patients with macrolide-resistant blood isolates of S pneumoniae.39 This study further described the treatment failure of 19 patients with bacteremia caused by erythromycin-resistant S pneumoniae. The study authors concluded that the development of breakthrough bacteremia during macrolide therapy is more likely to occur in patients infected with an erythromycin-resistant pneumococcus.39Acute Respiratory Tract Infection Paper

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