Pneumonia

  • Antibiotic and Antiviral Drug Classes


    Beta-Lactams

    Beta-lactam antibiotics share common chemical features. They include penicillins, cephalosporins, and some newer similar medications. They interfere with bacterial cell walls.

    Penicillins. Penicillin was the first antibiotic. There are many forms of this still-important drug:

    • 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 inexpensive and, at one time, was highly effective against S. pneumoniae. Unfortunately, bacterial resistance to amoxicillin has increased significantly, both among S. pneumoniae and H. influenzae. Ampicillin is similar and is an alternative to amoxicillin, but requires more doses and has more severe gastrointestinal side effects.
    • Amoxicillin-clavulanate (Augmentin) is a type of penicillin that works against a wide variety of bacteria. An extended-release form has been approved for treating adults with community-acquired pneumonia caused by bacterial strains that have become partially resistant to penicillin.
    • Antistaphylococcal penicillins were developed to treat Staphylococcus aureus. The standard drug was methicillin, but it is no longer used routinely, due to very high rates of resistance in hospital-acquired pneumonias. Resistance in community-acquired Staphylococcus aureus is also increasing. Alternatives include vancomycin and linezolid. There are also other options for this type of bacteria.
    • Penicillins used against Pseudomonas aeruginosa include ticarcillin and piperacillin. Piperacillin is more effective than ticarcillin.

    Many people have a history of an allergic reaction to penicillin, but research suggests that the allergy may not occur again in a significant number of adults. Skin tests are available to help determine if those with a history of penicillin allergies could use these important antibiotics.

    Cephalosporins. Most of these antibiotics are not very effective against bacteria that have developed resistance to penicillin. They are classed according to their generation:

    • First generation includes cephalexin (Keflex), cefadroxil (Duricef, Ultracef), and cephradine (Velosef).
    • Second generation includes cefaclor (Ceclor), cefuroxime (Ceftin), cefprozil (Cefzil), and loracarbef (Lorabid).
    • Third generation includes 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 include meropenem (Merrem), biapenem, faropenem, ertapenem (Invanz) and combinations [imipenem/cilastatin [Primaxin)]. These drugs are used to treat a wide variety of bacteria. They are now used for serious hospital-acquired infections and for bacteria that have become resistant to other beta-lactams. Imipenem has serious side effects when used alone, so it is given in combination with cilastatin to offset these adverse effects. The newer drugs are less toxic, although they may not be as effective.

    Sanfetrinem, a new beta-lactam antibiotic known as a trinem, is proving to be effective against S. pneumoniae, H. influenzae, and M. catarrhalis.

    Ceftobiprole is an investigational beta-lactam for methicillin-resistant Staphylococcus aureus (MRSA), penicillin-resistant streptococci, and other Gram-negative bacteria. Other anti-MRSA beta-lactams in development include:

    • CS-023/RO-4908463, a carbapenem
    • Ceftaroline, a cephalosporin (PPI-0903)

    Fluoroquinolones

    Fluoroquinolones (quinolones) interfere with bacteria's genetic material to prevent them from reproducing.

    • Ciprofloxacin (Cipro), a second-generation quinolone, remains the most potent quinolone against Pseudomonas aeruginosa. It is not very effective against Gram-positive bacteria such as Streptococcus pneumoniae.
    • "Respiratory" quinolones are currently the most effective drugs available for a wide range of bacteria. Such drugs include levofloxacin (Levaquin) and gemifloxacin (Factive). Some of the newer fluoroquinolones only need to be taken once a day.
    • The fourth-generation quinolones moxifloxacin (Avelox) and clinafloxacin (which is still under development) are proving to be effective against anaerobic bacteria.

    S. pneumoniae -- strains resistant to the "respiratory" quinolones are uncommon in the U.S., but resistance is dramatically increasing.

    Many quinolones cause side effects, including:

    • Nervous system, mental, and heart problems
    • Sensitivity to light

    Pregnant women should not take these medications. The drugs also enhance the potency of oral anti-clotting drugs.

    Macrolides, Azalides, and Ketolides

    Macrolides and azalides also affect the genetics of bacteria. These medications include:

    • Azithromycin (Zithromax, Zmax)
    • Clarithromycin (Biaxin)
    • Erythromycin
    • Roxithromycin (Rulid)

    These antibiotics are effective against atypical bacteria such as mycoplasma and chlamydia. Macrolides are also used in some cases for S. pneumoniae and M. catarrhalis, but there is increasing bacterial resistance to these antibiotics. All but erythromycin are effective against H. influenzae. Macrolide-resistance rates doubled between 1995 and 1999 as more and more children were being treated with these antibiotics. Some research suggests these drugs may reduce the risk of a first heart attack in some patients by reducing inflammation in the blood vessels.

    Extended-release (ER) azithromycin (Zmax) is the first anti-pneumonia antibiotic that can be given in a single dose. It is effective against Gram-positive, Gram-negative, and atypical bacteria. Studies have shown the results to be equal to those achieved with 7 days of levofloxacin or clarithromycin ER in patients with CAP. A single-dose antibiotic decreases the likelihood that a patient will stop taking the antibiotic early, which rapidly contributes to the development of drug-resistant bacteria.

    Ketolides. Ketolides are a new class of antibiotic drugs. They are derived from erythromycin and were developed to combat bacteria that have become resistant to macrolides. Telithromycin (Ketek), the first antibiotic in the ketolide class, was approved by the FDA in 2004 for treating community-acquired pneumonia (CAP).

    In February 2007, the FDA withdrew approval of Ketek for the treatment of acute bacterial sinusitis. The agency decided that the serious risks of telithromycin outweigh its benefits for sinusitis treatment. The decision followed several 2006 reports of patient deaths due to severe liver damage.

    Telithromycin is still approved for the treatment of CAP, but the drug carries a black box warning noting the potentially serious side effects, including:

    • Liver failure
    • Loss of consciousness
    • Nerve and muscle (neuromuscular) problems
    • Vision problems

    Because of these side effects, telithromycin is only approved for patients with mild-to-moderate community-acquired pneumonia caused by penicillin- or macrolide-resistant S. pneumoniae. Other treatments are as effective, and are safer.

    Tetracyclines

    Tetracyclines inhibit the growth of bacteria. They include doxycycline, tetracycline, and minocycline. They can be effective against S. pneumoniae and M. catarrhalis, but bacteria that are resistant to penicillin are also often resistant to doxycycline. The side effects of tetracyclines include:

    • Burning in the throat
    • Skin reactions to sunlight
    • 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 applying a solution directly to mucus membranes, skin, or body cavities. They can have very serious side effects, including:

    • Balance problems
    • Hearing damage
    • Kidney damage

    Lincosamides

    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) are used for Staphylococcus aureu s infections that have become resistant to standard antibiotics. The drug can be taken by mouth or given intravenously. The latest generation of glycopeptides, a derivative of vancomycin, is called telavancin. In studies of hospital-acquired pneumonia, it has shown promise for the treatment of Gram-positive pneumonia.

    Trimethoprim-Sulfamethoxazole

    Trimethoprim-sulfamethoxazole (Bactrim, Cotrim, Septra) is less expensive than amoxicillin. It is particularly useful for adults with mild bacterial upper respiratory infections who are allergic to penicillin. The drug is no longer effective against certain streptococcal strains. It should not be used in patients whose infections occur after dental work, or in people who are allergic to sulfa drugs. Allergic reactions can be very serious.

    Oxazolidinone

    Linezolid (Zyvox) is the first antibacterial drug in a new class of man-made antibiotics called oxazolidinones. It has been shown to work against certain aerobic Gram-positive bacteria.

    Other Medications

    Inhaled polymyxin, a drug used in cystic fibrosis patients, is showing some effectiveness against pneumonia caused by multidrug-resistant Gram-negative bacteria, including pseudomonas and klebsiella.