Antibiotics to treat Pneumonia

MRC scientists have recently discovered that a significant proportion of pneumonia in children is not caused by a virus, but by a bacterium - the pneumococcus. This has important implications for the treatment of children.

World Health Organisation statistics state pneumonia as the leading cause of death in children worldwide. Almost four million children die of the disease each year - most of them in developing countries.

Almost a year ago, scientists from the MRC's Respiratory and Meningeal Pathogens Research Unit proved that a 9-valent pneumococcal vaccine significantly reduced pneumonia, pneumococcal disease and antibiotic-resistant pneumococcal disease among forty thousand infant trial participants in Soweto. An added bonus was that the vaccine also showed promise in the treatment of HIV-positive infants.

Now further analysis of trial results has shown that 31% of children's pneumonias, previously thought to be caused only by viruses, are in fact caused by a bacterium. This was proved by the fact that the pneumococcal vaccine prevented viral-associated pneumonia in the children.

According to Prof Keith Klugman, the director of the unit, the findings are important for a number of reasons. "They show that children in hospital with severe pneumonia need antibiotics."

A viral illness (such as a cold or flu) is not treated with antibiotics; this medication is only effective for a bacterial infection. The reason is that antibiotics target the cell wall and metabolism of bacteria, and a virus does not have a cell wall. Since viruses also have different metabolic pathways to bacteria, antibiotics are completely ineffective.

"Up until now, the emphasis has been to try and find out whether the infection was caused by a virus or a bacterium before starting treatment. But this shows that by the time a child reaches hospital, the virus and the bacterium are working together, so treatment with an antibiotic will be effective."

The results have been very encouraging: Prof Klugman says the vaccine is better at preventing pneumonia than was previously thought.

The results also show the extent of the collaboration between viruses and bacteria in causing human illness. "Our evidence shows that what starts out as a viral infection often ends in a bacterial infection.

We think that between one third and one half of all viral pneumonia infections are actually caused by the pneumococcus bacterium.

The results show that the vaccine reduces pneumonia associated with respiratory viral infections, because it prevents the bacterium from infecting a child who might already be struggling with a viral infection."

Antibiotic Classes

Beta-Lactams

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. Amoxicillin (Amoxil, Polymox, Trimox, Wymox, or any generic formulation) is probably the most common penicillin. It 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 .

Amoxicillin-clavulanate (Augmentin) is known as an augmented penicillin, which works against a wide spectrum of bacteria. Ampicillin, also a form of penicillin, is an equally inexpensive alternative to amoxicillin but requires more doses and has more severe gastrointestinal side effects than amoxicillin.

Cephalosporins. These agents have also become less effective against S. pneumoniae . They are often classed in the following:

First generation includes cephalexin (Keflex), cefadroxil (Duricef, Ultracef), and cefaclor (Ceclor). These agents may be useful for gram-positive organisms, except resistant S. pneumoniae.

Second and third generation include cefuroxime (Ceftin), cefpodoxime (Vantin), loracarbef (Lorabid), cefditoren (Sprectracef), cefixime (Suprax), and ceftibuten (Cedex). These are effective against a wide range of gram-negative bacteria. Most are not very effective against Staphylococcus or S. pneumoniae bacteria that have developed resistance to penicillin.

Newer Beta-Lactam Agents.

Carbapenems include meropenem (Merrem), 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 drugs.

Imipenem has serious side effects used alone so it is given in combinations with another agent, cilastatin, to offset these adverse effects.

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 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 wide 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 makes compliance easier. A few of the third-generation quinolones cause photosensitivity (eg, sparfloxacin).

A fourth generation includes moxifloxacin (Avelox), trovafloxacin, and clinafloxacin. Studies on moxifloxacin are indicating that it is safe and effective against many gram-negative and gram-positive bacteria.

Macrolides and Azalides

Macrolides and azalides are antibiotics that also effect 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. Except for erythromycin they are effective against H. influenzae . A new once-a-day formulation (Biaxin XL) is now available

Tetracyclines

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.

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.

Aminoglycosides

Aminoglycosides are given by injection for very serious bacterial infections. (gentamicin, kanamycin, tobramycin, amikacin). 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 many S. pneumoniae bacteria but not against H. influenzae.

Glycopeptide

Glycopeptides (vancomycin, teicoplanin) is used for Staphylococcus aureu s that have become resistant to standard antibiotics. It is available in intravenous and oral forms. Resistance to this drug is growing.

Ketolides

Telithromycin (Ketek) is the first antibiotic in the ketolide class. It is has been approved for treating community acquired pneumonia and is showing great promise in treating many of the otherwise antibiotic-resistant bacterial strains. Studies on long term-safety are still needed.

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).

Streptogrammins

Quinupristin/dalfopristin [Syndercid].

How Aspirin Could Be Better Used

ASPIRIN, known to prevent heart attacks and strokes in thousands of people at high risk of cardiovascular disease, is still massively under-used according to a new United Kingdom study.

Previous surveys show that aspirin (and other antiplatelet drugs) could prevent about 100,000 premature deaths worldwide every year, including at least 7,000 annually in the UK alone.

The latest report from the Antithrombotic Trialists' Collaboration funded by the British Heart Foundation (BHF) and the Medical Research Council (MRC) strengthens and extends the evidence but states that in the UK and the United States, fewer than half of patients with high-risk conditions are prescribed aspirin.

The largest international overview of disease treatment involving more than 200,000 patients in 300 clinical trials was coordinated by scientists from Oxford University's Clinical Trial Service Unit.

Dr Colin Baigent, the MRC scientist who led the research, said: "This study shows that aspirin is beneficial in an even wider range of conditions than previously believed. What we now need is to ensure that aspirin, or some other antiplatelet drug, is routinely considered for patients who might need it."

One of the main reasons for the under-use of aspirin could be the lack of clear advice from some national guidelines on the effectiveness of the drug for patients who are at increased risk of vascular disease but have not yet suffered a heart attack or stroke.

"Worryingly, surveys in the UK have shown that aspirin is prescribed to less than a quarter of people with ailments such as peripheral arterial disease - a condition which causes fatty deposits to build up in leg arteries - in which heart attacks and strokes are common.

We believe that aspirin has helped to protect these high-risk patients but despite this many people will die from their very first heart attack, by which time aspirin is too late," said Dr Baigent.

Compiled by Jim Kelsey

The research team hopes that the report will help to dispel any remaining uncertainty among doctors and lead to an increase in the prescribing of aspirin, an effective and inexpensive drug.n

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