Dozens of antibiotics are available that can treat most cases of pneumonia in or out of the hospital, but it is sometimes difficult for the physician to select the best drug. Often the infecting organism remains unknown even after testing. In determining the appropriate antibiotic, the physician must first answer a number of questions:
- How severe is the pneumonia? Mild-to-moderate cases can be treated at home with oral antibiotics while severe pneumonia usually requires intravenous antibiotics administered in the hospital.
- If the organism causing the pneumonia is not known, was the disorder community-acquired pneumonia (CAP) or hospital-acquired (also called nosocomial)? Different organisms are usually involved in each setting, and the physician can often use this information to guess the most likely organism causing the pneumonia.
- If the organism is known, is it typical or atypical? Typical bacterial, community acquired pneumonias for example, are usually caused by Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis, which have traditionally been treated with penicillin or other standard antibiotics. Such antibiotics, however, do not affect atypical organisms, such as Legionella, Mycoplasma, or Chlamydia. (These organisms are generally treated with a macrolide or possibly a newer quinolone.)
- Does the patient have an impaired immune system, such as in AIDS? Antibiotics used to treat such patients may differ from those used in patients with healthy immune systems.
Once an antibiotic has been chosen, there are still difficulties:
- Individuals respond differently to the same antibiotic depending on age, health, size, and other factors.
- Patients can be allergic to certain antibiotics, thus requiring alternatives.
- Patients may harbor strains of bacteria that are resistant to certain antibiotics.
Antibiotic Treatments for Community-Acquired Pneumonia
Many cases of community-acquired pneumonia are caused by Streptococcus (S.) pneumoniae, which usually responds to antibiotics known as beta lactams (which include penicillin).
However, other important causes of CAP, particularly in younger people, are atypical bacteria, which respond to macrolides (either erythromycin, clarithromycin, or azithromycin) or newer quinolones. Such quinolones include levofloxacin (Levaquin), gatifloxacin (Tequin), gemifloxacin (Factive), and moxifloxacin (Avelox). (In most cases, unlike macrolides, the newer quinolones are also active against penicillin-resistant S. pneumoniae. )
The standard treatment, then, for community-acquired pneumonia in most patients is a combination of a beta-lactam and a macrolide or quinolone.
Oral antibiotics are generally sufficient for patients whose CAP is mild enough to be treated at home. Intravenous antibiotics are required for hospitalized patients with CAP.
Antibiotic Treatments for Hospital-Acquired (Nosocomial) Pneumonia
Gram-Positive Pneumonia. S. aureus is common in nosocomial pneumonia and is a potentially life-threatening infection. Resistance to penicillin is the rule in these cases but certain specialized penicillins such as nafcillin are often still effective. The alternatives to penicillins are first- or second generation cephalosporins. Unfortunately, resistance to these agents is increasing as well. Vancomycin is used for highly resistant bacteria.
Gram-Negative Pneumonia. Patients with hospital-acquired pneumonia are at high risk for infection from gram-negative organisms. Such organisms include Pseudomonas aeruginosa and Klebsiella pneumonia, which require aggressive specific therapy. Powerful antibiotics used against these organisms include the fourth-generation cephalosporins, carbapenems, or ciprofloxacin alone or in combination with an aminoglycides (entamicin or tobramycin). Multidrug therapy may be necessary, particularly for patients, such as those who are on mechanical ventilators, who are at very high risk for multiple dangerous organisms.
Antibiotics for P. Carinii Pneumonia (Common in HIV-Positive Patients)
Trimethoprim-sulfamethoxazole is the antibiotic combination that is the first choice for both preventing and treating P carinii pneumonia in HIV-positive patients. Clindamycin-primaquine may be a good salvage treatment for patients who do not respond to standard therapies.
Side Effects of Antibiotics
Most antibiotics have the following side effects (although specific antibiotics may have other side effects or fewer of the standard ones).
- The most common side effect for nearly all antibiotics is gastrointestinal distress.
- Antibiotics double the risk for vaginal infections in women. Taking supplements of acidophilus or eating yogurt with active cultures may help restore healthy bacteria that offset the risk for such infections.
- Allergic reactions can also occur with all antibiotics but are most common with medications derived from penicillin or sulfa. These reactions can range from mild skin rashes to rare but severe, even life-threatening anaphylactic shock.
- Certain drugs, including some over-the-counter medications, interact with antibiotics; patients should inform the physician of all medications they are taking and of any drug allergies.
The beta-lactam antibiotics share common chemical features and 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. An extended release form has been approved for treating adults with community-acquired pneumonia caused by bacterial strains that have become resistant to penicillin.
- Antistaphylococcal penicillins were developed to treat Staphylococcus aureus. The standard agent was methicillin, but it not used very much because of very high rates of resistance in hospital-acquired pneumonias. (Resistance in community-acquired Staphylococcus aureus is being reported.) Alternatives include nafcillin, oxacillin, cloxacillin, and dicloxacillin.
- Certain penicillins are used against Pseudomonas aeruginosa, include ticarcillin and piperacillin. Piperacillin is the most effective of these agents for this dangerous organism.
Many people have a history of an allergic reaction to penicillin, but some evidence is suggesting that the allergy may not recur in a significant number of adults. Skin tests are available that could determine if some people previously 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 (also simply called quinolones) interfere with the bacteria's genetic material so they cannot reproduce. Quinolones are not only effective against many common bacteria, but they can also be used to treat tuberculosis. (This is potentially a problem when they are used to treat other infections, such as pneumonia, in people who harbor the TB organism. In such cases, quinolones may mask and delay diagnosis and treatment of TB.)
- Ciprofloxacin (Cipro), a second-generation quinolone, remains the most potent quinolone against Pseudomonas aeruginosa bacteria but is not very effective for gram-positive bacteria, which includes Streptococcus pneumoniae. Ofloxacin (Floxin) is generally used in drops for ear infections.
- 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). Some of the newer fluoroquinolones only need to be taken once a day, which make compliance easier.
- A fourth generation includes moxifloxacin (Avelox) and clinafloxacin are proving to be effective against anaerobic bacteria.
S. pneumoniae-strains resistant to the quinolones have been uncommon in the US but resistance has dramatically increased in the past few years, particularly with ciprofloxacin.
Many quinolones have adverse effects, including neurologic and psychiatric problems, photosensitivity, and effects on the heart. Pregnant women should not take these agents. They also enhance the potency of oral anti-clotting agents.
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 the atypical bacteria, including Mycoplasma or Chlamydia. They are also used in some cases for S. pneumoniae and M. catarrhalis, but there is increasing bacterial resistance to these agents. Except for erythromycin they 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 is suggesting that these agents may reduce the risk for a first heart attack in some patients by reducing inflammation in the blood vessels.
Ketolides. 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 inhibit bacterial growth. 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. Tetracyclines have unique side effects among antibiotics, including skin reactions to sunlight, possible burning in the throat, and tooth discoloration.
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.
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 (vancomycin, teicoplanin) is used for Staphylococcus aureus that have become resistant to standard antibiotics. They are available in intravenous and oral forms.
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.
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).
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.
Preventing and Treating Respiratory Syncytial Virus (RSV) Pneumonia in Children
Prevention of RSV. Two agents have been approved for protecting high-risk infants against RSV pneumonia:
- Palivizumab (Synagis) is known as a monoclonal antibody, a genetically engineered antibody, which targets the RSV virus.
- RSV immune globulin (RespiGam) is made up of antibodies to RSV that are obtained from the blood of healthy infants.
RespiGam must be administered intravenously while Synagis can be injected.
Treatment of RSV. Ribavirin is the first treatment approved for respiratory syncytial virus pneumonia, although it has only modest benefits. The American Academy of Pediatrics recommends it for children at high risk for serious complications of RSV. In one study, a combination of ribavirin with RSV immune globulin was more effective than either drug alone.
Drugs that open the airways of the lungs, known as bronchodilators, are sometimes used to treat RSV infection, but evidence on their benefits is conflicting. One study of albuterol, a common bronchodilator, however, indicated that epinephrine may be more effective.