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The primary choice of agent still includes the less expensive antibiotics, such as amoxicillin/clavulanate, doxycycline and trimethoprim-sulfamethoxazole. Antibiotic classes known as the macrolides and quinolones appear to be beneficial as well. Detecting the specific organism causing the lung infection is often difficult. [For more information, seeWell-Connected Report #64, Pneumonia.]
Preventive (Prophylactic) Antibiotics in COLD Patients. In the past, antibiotics were given daily for patients with even mild COLD until studies found that they did not alter progression of either the disorder or the disabilities associated with it. Preventive antibiotics may be give one week a month with alternative agents. They are now prescribed only for COLD patients with one or more of the following conditions:
- Having four or more episodes a year of acute infection with intensified COLD symptoms, including worsened shortness of breath and mucus production.
- Having deficient immune systems.
- Having bronchiectasis, an irreversible lung disease in which the airways in the lung are chronically dilated.
Antibiotic Options
Beta-Lactams
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The beta-lactam antibiotics include penicillins, cephalosporins, and some newer similar agents. Their primary actions to interfere with bacterial cell walls.
Penicillins. Penicillin was the first antibiotic. There are many forms to this still-important agent:
- Natural penicillins include penicillin G (for intravenous use) and V (for oral use).
- Penicillin derivatives called aminopenicillins, particularly amoxicillin (Amoxil, Polymox, Trimox, Wymox, or any generic formulation), are now the most common penicillins used. Amoxicillin is both inexpensive and at one time was highly effective against the S. pneumoniae bacteria. Unfortunately, bacterial resistance to amoxicillin has increased significantly, both among S. pneumoniae and H. influenzae. Ampicillin is similar, and an alternative to amoxicillin, but requires more doses and has more severe gastrointestinal side effects than amoxicillin. Amoxicillin-clavulanate (Augmentin) is known as an augmented penicillin, which works against a wide spectrum of bacteria.
Many people have a history of an allergic reaction to penicillin, but some evidence suggests that the allergy may not persist in a significant number of adults. Skin tests are available to help determine if some people previously considered allergic could use these important antibiotics.
Cephalosporins. These agents have also become effective against S. pneumoniae or Staphylococcus aureus. Most are not very effective against bacteria that have developed resistance to penicillin. They are often classed in the following:
- First generation includes cephalexin (Keflex), cefadroxil (Duricef, Ultracef), and cephradine (Velosef).
- Second generation include cefaclor (Ceclor), cefuroxime (Ceftin), cefprozil (Cefzil), and loracarbef (Lorabid),
- Third generation include cefpodoxime (Vantin), cefdinir (Omnicef) cefditoren (Sprectracef), cefixime (Suprax), and ceftibuten (Cedex). Ceftriaxone (Rocephin) is an injected cephalosporin. These are effective against a wide range of gram-negative bacteria.
Other Beta-Lactam Agents. Carbapenems (also known as thienamycins) include meropenem (Merrem), biapenem, faropenem, ertapenem (Invanz) and combinations (imipenem/cilastatin [Primaxin]). These agents cover a wide spectrum of bacteria. They are now used for serious hospital-acquired infection and for bacteria that have become resistant to other beta-lactam bacteria. Imipenem has serious side effects used alone so in given in combinations with another agent, cilastatin, to offset these adverse effects. The newer agents are less toxic, although they may not be as potent.
Sanfetrinem, a novel beta-lactam antibiotic known as a trinem, is proving to be effective against S. pneumoniae,H. influenzae, and M. catarrhalis.
Fluoroquinolones (Quinolones)
Fluoroquinolones (also simply called quinolones) interfere with the bacteria's genetic material so they cannot reproduce.
- Ciprofloxacin (Cipro), a second-generation quinolone, remains the most potent antipseudomonal quinolone against Pseudomonas aeruginosa bacteria, but is not very effective for gram-positive bacteria.
- Newer third-generation quinolones are currently the most effective agents against a wider range of common bacteria. They include levofloxacin (Levaquin), sparfloxacin (Zagam), gemifloxacin (Factive), and gatifloxacin (Tequin). Levofloxacin is the first drug approved specifically for penicillin-resistant S. pneumoniae. Some of the newer fluoroquinolones also only need to be taken once a day, which make compliance easier. Some, but not all, quinolones cause photosensitivity.
- A fourth generation includes moxifloxacin (Avelox), trovafloxacin, and clinafloxacin, which are proving to be effective against anaerobic bacteria. Studies suggest that taking the moxifloxacin once a day offered fast relief for patients with acute exacerbations of chronic bronchitis.
Macrolides, Azalides, and Ketolides
Macrolides and azalides are antibiotics that also affect the genetics of bacteria. They include erythromycin, azithromycin (Zithromax), clarithromycin (Biaxin), and roxithromycin (Rulid). These antibiotics are effective against S. pneumoniae and M. catarrhalis, but there is increasing bacterial resistance to these agents. In one study, patients who took erythromycin during a common cold had a lower risk for worsened COLD symptoms than those not taking the antibiotic.
Ketolides are drugs derived from erythromycin that were developed to combat organisms that have become resistant to macrolides. Telithromycin (Ketek), the first antibiotic in the ketolide class, is being evaluated for FDA approval for treating community-acquired pneumonia (CAP), chronic obstructive lung disease, and acute sinusitis.
Tetracyclines
Tetracyclines inhibit bacterial growth. They include doxycycline, tetracycline, and minocycline. Doxycycline can be effective for COLD patients, but bacteria that are resistant to penicillin are also often resistant to doxycycline. Tetracyclines have unique side effects among antibiotics, including skin reactions to sunlight, possible burning in the throat, and tooth discoloration.
Aminoglycosides
Aminoglycosides (gentamicin, kanamycin, tobramycin, amikacin) are given by injection for very serious bacterial infections. They can be given only in combination with other antibiotics. Some are available in inhaled forms or by irrigation (applying a solution directly to mucous membranes, skin, or body cavity). They can have very serious side effects, including damage to hearing, sense of balance, and kidneys.
Lincosamide
Lincosamides prevent bacteria from reproducing. The most common lincosamide is clindamycin (Cleocin). This antibiotic is useful against S. pneumoniae and S. aureus but not against H. influenzae.
Glycopeptides
Glycopeptides (vancomycin, teicoplanin) is used for Staphylococcus aureus that have become resistant to standard antibiotics. They are available in intravenous and oral forms.
Trimethoprim-Sulfamethoxazole
Trimethoprim-sulfamethoxazole (Bactrim, Cotrim, Septra) is less expensive than amoxicillin and particularly useful for adults with mild bacterial upper respiratory infections who are allergic to penicillin. It is no longer effective, however, against certain streptococcal strains. It should not be used in patients whose infections occurred after dental work or in patients allergic to sulfa drugs. Allergic reactions can be very serious.
Oxazolidinone
Linezolid (Zyvox) is the first antibacterial drug in a new class of synthetic antibiotics called oxazolidinones. It has been proven effective against certain aerobic gram-positive bacteria, including Staphylococcus aureus (MRSA).
Others
Streptogrammins (quinupristin/dalfopristin [Syndercid]). In a major 2001 study of S. pneumonia resistance to antibiotics, there were no reports yet of resistance to this agent.
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Treatment for AAT Deficiency
Replacement Treatment. Augmentation or replacement therapy supplements the existing alpha 1-antitrypsin (AAT) levels in the blood. The replacement AAT is derived from human blood, which has been screened for viruses and is injected weekly or bimonthly. One study reported that patients taking this supplement had a mortality rate that was two thirds of those not on this therapy. Replacement therapy may also reduce the severity and frequency of lung infections. Therapy is life long. Patients with inherited AAT deficiency, regardless of their smoking history, are eligible for this therapy. Unfortunately, this therapy is in short supply.
An inhaled AAT replacement treatment produced from the milk of genetically bred sheep is under investigation. An oral forms is also under investigation.
Other Investigative Treatments for AAT Deficiency. Aerosolized hyaluronic acid may protect lungs from injury by elastase, the enzyme that causes lung tissue to lose elasticity. A clinical trial is underway.
Agents That Loosen Lung Secretions
Patients with persistent coughing and sputum often use agents that loosen secretions and help move them out of the lungs. However, it is not clear if these agents offer any important benefits.
Expectorants. Expectorants, such as guaifenesin (found in common cough remedies), stimulate the flow of fluid in the airways and help move secretions using cilia motion (the hair-like structures in the lung) and coughing.
Mucolytics. Mucolytics contain ingredients such as iodinated glycerol or acetylcysteine that make sputum more watery and so easier to cough up. (Acetylcysteine also acts as an antioxidant, which could provide additional value.) Although there is some controversy over their value, an analysis of many studies indicated that oral mucolytics reduce the number of symptoms in patients with severe chronic bronchitis and have a small but significant effect on breathing function. They should not be used, however, during an acute attack, since they may worsen lung function. They also do not appear to be very helpful for patients with mild COLD.
Experimental Therapies
Selective Phosphodiesterase 4 Inhibitors. Cilomilast (Ariflo) and roflumilast (Daxas) are selective phosphodiesterase 4 (PDE4) inhibitors. They block PDE4, an enzyme that is overproduced in COLD and asthma and causes inflammation in the airways. Studies are very promising. A 2003 report on reflumilast, for example, found significant improvement in lung function and quality of life compared to placebo. The drugs can cause diarrhea and nausea, which may limit their tolerability.
Leukotriene-Antagonists. Leukotriene-antagonists (also called anti-leukotrienes) are oral medications that block leukotrienes. These are powerful chemicals in the immune system that, in excess, produce inflammation and spasms in the airways. Agents include zafirlukast (Accolate), montelukast (Singulair), zileuton (Ziflo), and pranlukast (Ultair, Onon). They are currently used for preventing asthma attacks. Studies are now indicating they also have benefits for people with COLD, although it is not clear if they have advantages over standard COLD agents
Retinoic Acid. All trans retinoic acid (ATRA), which is a derivative of vitamin A, may reverse some of the damage that occurs in emphysema. One such agent is being developed that researchers hope will grow new air sacs in the lungs.
Sildenafil. Interesting research is suggesting that some men with COLD who take sildenafil (Viagra) experience modest improvement in lung function.
Testosterone Replacement. People with COLD tend to have low levels of testosterone. Researchers are investigating testosterone replacement in both men and women with COLD for increasing muscle strength and function.
P2Y(2) Receptor Agonists. P2Y(2) receptor agonists are experimental agents that increase the action of the cilia (hair-like structures) in the lung and clear out mucus. The most promising agent to date is currently referred to as INS37217.
Other Investigative Agents. A number of agents are in very early stages of investigation. They include drugs called antiproteases (e.g., sivelestat ONO-6818. batimastat), new antioxidants, and many others.
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