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Antibiotics in nutshell!!!

Posted Sep 25 2009 10:13pm
An antibiotic is a substance or compound that kills or inhibits the growth of bacteria. Antibiotics can be broadly classified as either bactericidal or bacteriostatic. Bactericidals kill bacteria directly where bacteriostatics prevent cell division. Antibiotics which target the bacterial cell wall (penicillins, cephalosporins), or cell membrane (polymixins), or interfere with essential bacterial enzymes (quinolones, fluroquinolone) usually are bactericidal in nature. Those which target protein synthesis, such as the aminoglycosides, macrolides and tetracyclines, are usually bacteriostatic. Anti-bacterial antibiotics can be also categorized based on their target specificity: "narrow-spectrum" antibiotics target particular types of bacteria, such as Gram-negative or Gram-positive bacteria, while broad-spectrum antibiotics affect a wide range of bacteria.

Gram-positive bacteria: Gram-positive bacteria are characterized by having as part of their cell wall structure, peptidoglycan as well as polysaccharides and/or teichoic acids. Examples of Gram-positive bacteria include Staphylococcus, Streptococcus, Enterococcus, (which are cocci), and Bacillus, Corynebacterium, Nocardia, Clostridium, Actinobacteria, and Listeria (which are rods). Gram-positive can cause a wide variety of diseases in humans such as food poisoning, wound infection, Urinary tract infections, besides Pneumonia, Meningitis, Osteomyelitis, Endocarditis, Toxic shock syndrome (TSS), Diverticulitis, Septicemia, etc.

Gram-negative bacteria: The cell envelope of Gram-negative Bacteria contains an additional outer membrane composed by phospholipids and lipopolysaccharides which face the external environment. The highly charged nature of lipopolysaccharides confers an overall negative charge to the Gram negative cell wall. Examples of Gram-negative bacteria include Escherichia coli, Salmonella, Shigella, and other Enterobacteriaceae, Pseudomonas, Moraxella, Helicobacter, Neisseria, Klebsiella, Hemophilus, Legionella, etc. The diseases caused by Gram-negative bacteria include Diarrhea, Gastroenteritis, Peritonitis, Septicemia, Pneumonia, Neonatal meningitis, Urinary tract infection, Typhoid fever, food poisoning, Ulcer, Upper and lower respiratory tract infection, burn and wound infection, Otitis media, Meningitis, Sexually transmitted disease like Gonorrhoea and other infections of genital system, etc. Treponema pallidum, which causes Syphilis, a sexually transmitted disease, is classified as Spirochaetes, which belong to a phylum of distinctive Gram-negative bacteria, which have long, helically coiled (spiral-shaped) cells. Other members of this phylum include Leptospira species, which causes Leptospirosis and Borrelia recurrentis, which causes Relapsing fever.

Certain bacteria like Mycobacterium tuberculosis, which cause Tuberculosis (TB) and Mycobacterium leprae, which cause Leprosy, can neither be classified as Gram-positive or Gram-negative. They are classed as Aerobic bacteria as they require high levels of oxygen to grow.

Anaerobic bacteria are bacteria that do not live or grow in the presence of oxygen. The main Anaerobic Gram-positive cocci that produce disease are the peptococci and the peptostreptococci. Clostridium belongs to Gram-positive anaerobic bacteria. The four main spieces of Clostridium known to cause diseases in humans include, C. botulinum-which causes botulism, C. difficile-which causes colitis, C. perfringens-which causes gas gangrene and C.tetani-which causes Tetanus. Anaerobic gram-negative bacilli include Bacteroides fragilis, Prevotella melaninogenica, and Fusobacterium species. Anaerobic bacteria can be the major cause of infection in the pleural spaces and lungs; in Intra-abdominal, Gynecologic, CNS, Upper respiratory tract, and cutaneous diseases; and in Bacteremia. Usually the Anaerobic bacteria are accompanied by Aerobes, and the resulting infection is known as 'Mixed anaerobic infection'. Anaerobic infections can be identified by foul smelling pus at the site of infection, especially in case of infected wounds.

Classification of antibiotics

Penicillins

The penicillins are the oldest classes of antibiotics.Penicillins are generally bactericidal, inhibiting formation of the cell wall. Penicillins are used to treat skin infections, Dental infections, Ear infections, Respiratory tract infections, Urinary tract infections, Gonorrhea, etc.

The types of Penicillins include:

The natural penicillins, which are based on the original penicillin-G structure. Penicillin-G types are effective against gram-positive strains of streptococci, staphylococci, and some gram-negative bacteria such as Meningococcus.

Penicillinase-resistant penicillins, notably Methicillin and Oxacillin, are active even in the presence of the bacterial enzyme that inactivates most natural penicillins. Extended spectrum Penicillins are effective against a wider range of bacteria.

Cephalosporins

Cephalosporins have a mechanism of action identical to that of the penicillins. However, the basic chemical structure of the penicillins and cephalosporins differs in other respects, resulting in some difference in the spectrum of antibacterial activity. Cephalosporins are used to treat Pneumonia, Respiratory tract infections like strep throat, Tonsillitis, Bronchitis; Staph infections, Otitis media, various types of skin infections, Gonorrhea, Urinary tract infections. Cephalosporin antibiotics are also commonly used for surgical prophylaxis. They can also be used to treat Bone infections.

Cephalosporins are grouped into "generations" by their antimicrobial properties. Each newer generation has a broader spectrum of activity than the one before.

The first generation Cephalosporins: They possess generally excellent coverage against most Gram-positive pathogens and variable to poor coverage against most Gram negative pathogens. The first generation Cephalosporins include, Cefazolin, Cephalexin, Cefadroxil.

The second generation Cephalosporins: In addition to the Gram positive spectrum of the first generation Cephalosporins, these agents have expanded Gram negative spectrum. The second generation Cephalosporins include: Cefaclor, Ceforanide, Cefuroxime.

The third generation Cephalosporins: They have much expanded Gram negative activity. However, some members of this group have decreased activity against Gram-positive organisms.They include, Cefixime, Cefodizime, Cefoperazone, Cefotaxime, Cefpodoxime, Ceftriaxone.

The fourth generation Cephalosporins are extended-spectrum agents with similar activity against Gram-positive organisms as first-generation Cephalosporins. They also have a greater resistance to Beta-lactamases than the third generation Cephalosporins. Many fourth generation Cephalosporins can cross blood brain barrier and are effective in Meningitis. The fourth generation Cephalosporins include, Cefclidine, Cefepime, Cefluprenam, Cefozopran.

Fluroquinolones

Fluoroquinolones (fluoridated quinolones) are the newest class of antibiotics. Their generic name often contains the root "floxacin". They are synthetic antibiotics, and not derived from bacteria. Fluoroquinolones belong to the family of antibiotics called Quinolones. The older Quinolones are not well absorbed and are used to treat mostly urinary tract infections. The newer Fluroquinolones are broad-spectrum bacteriocidal drugs and because of their excellent absorption Fluroquinolones can be administered not only intravenously but orally as well. Fluoroquinolones are used to treat most common Urinary tract infections, Skin infections, and Respiratory infections (such as Sinusitis, Pneumonia, and Bronchitis). Commonly used Fluoroquinolones include Ciprofloxacin, Norfloxacin, Gatifloxacin, Ofloxacin.

Tetracyclines

Tetracyclines got their name because they share a chemical structure that has four rings. They are derived from a species of Streptomyces bacteria. Tetracycline antibiotics are broad-spectrum bacteriostatic agents that inhibit bacterial protein synthesis. Tetracyclines may be effective against a wide variety of microorganisms, including Rickettsia and Amebic parasites. Tetracyclines are used in the treatment of infections of the Respiratory tract, Sinuses, Middle ear, Urinary tract, Skin, Intestines. Tetracyclines also are used to treat Gonorrhoea, Typhus. Their most common current use is in the treatment of moderately severe Acne and Rosacea. The most commonly prescribed Tetracycline antibiotics are, Tetracycline, Doxycycline, Oxytetracycline.

Macrolides

The Macrolide antibiotics are derived from Streptomyces bacteria. The Macrolides are bacteriostatic, binding with bacterial ribosomes to inhibit protein synthesis. Macrolide antibiotics are used to treat Respiratory tract infections (such as Pharyngitis, Sinusitis, and Bronchitis), Genital, Gastrointestinal tract, and Skin infections. The most commonly prescribed Macrolide antibiotics include Erythromycin, Clarithromycin, Azithromycin, and Roxithromycin.

Aminoglycosides

Aminoglycoside antibiotics are used to treat infections caused by Gram-negative bacteria. Aminoglycosides may be used along with Penicillins or Cephalosporins to give a two-pronged attack on the bacteria. Aminoglycosides work quite well, but bacteria can become resistant to them. Since aminoglycosides are broken down easily in the stomach, they can't be given by mouth and must be injected. The most commonly-prescribed aminoglycoside include, Streptomycin, Amikacin, Gentamicin, Neomycin, Tobramycin.

Sulfonamides

They are competitive inhibitors of Folate synthesis. Folate is necessary for the cell to synthesize nucleic acids, and in its absence, cells of the bacteria will be unable to divide. They are used mostly to treat Urinary tract infection and include, Sulfamethizole, Trimethoprim, Trimethoprim-Sulfamethoxazole.

Carbapenems

Carbapenems have bactericidal activity against both Gram-positive and Gram-negative organisms and therefore useful for broad-spectrum antibacterial coverage. These include, Ertapenem, Doripenem, Imipenem, Meropenem.

Polypeptides

They are used to treat eye, ear, skin or bladder infections; usually applied directly to the eye/skin or inhaled into the lungs. These include Bacitracin, Polymyxin B.

Nitro-imidazole antibiotic

Nitro-imidazole antibiotics have a limited spectrum of activity that encompasses various protozoans and most Gram-negative and Gram-positive anaerobic bacteria. It has activity against protozoans like Entamoeba histolytica, Giardia lamblia and Trichomonas vaginalis. the most commonly prescribed Nitro-imidazole includes Metronidazole, besides Tinidazole and Ornidazole.

Metronidazole is indicated for the treatment of the following infections due to susceptible strains of sensitive organisms such as, Trichomoniasis, acute intestinal Amebiasis (amebic dysentery) and Amebic liver abscess, Anaerobic Bacterial Infections like Intra-abdominal infections, including peritonitis, intra-abdominal abscess, and liver abscess, Skin and skin structure infections, Gynecologic infections, Bacterial Septicemia, Bone and joint infections, as adjunctive therapy, Central Nervous System infections, including Meningitis and brain abscess, Lower Respiratory Tract infections, including Pneumonia, Empyema, and lung abscess, Endocarditis.

Others

Others include antituberculosis antibiotics like Ethambutol, Isoniazid, Rifampicin, Pyrazinamide. Chloramphenicol is used for treating various Gram-positive, Gram-negative and Anaerobic infections, besides Meningitis, MRSA and Cholera. Clindamycin and Lincomycin are used specially for treating Acne infections.

Side effects of antibiotics

Although antibiotics are generally considered safe and well tolerated, they have been associated with a wide range of adverse effects. Side effects may vary and can be very serious depending on the antibiotics used and the microbial organisms targeted. Side effects can range from fever and nausea to major allergic reactions. One of the more common side effects is diarrhea, sometimes caused by the anaerobic bacterium Clostridium difficile, which results from the antibiotic disrupting the normal balance of the intestinal flora, such overgrowth of pathogenic bacteria may be alleviated by ingesting probiotics during a course of antibiotics.

Alcohol and antibiotics

Alcohol can interfere with the activity or metabolization of antibiotics. It may affect the activity of liver enzymes, which break down the antibiotics. Moreover, certain antibiotics, including metronidazole, tinidazole, co-trimoxazole, cefoperazone, amoxicillin, cefmenoxime, and furazolidone, chemically react with alcohol, leading to serious side effects.

Resistance to antibiotics

The emergence of antibiotic resistance is an evolutionary process that is based on selection for organisms that have enhanced ability to survive doses of antibiotics that would have previously been lethal. Antibiotics like Penicillin and Erythromycin which used to be one-time miracle cures are now less effective because bacteria have become more resistant. Inappropriate antibiotic treatment and overuse of antibiotics have been a contributing factor to the emergence of resistant bacteria. One solution to combat resistance currently being researched is the development of pharmaceutical compounds that would revert multiple antibiotic resistances. These compounds include among others, Efflux inhibitors and Beta Lactamase inhibitors - Including Clavulanic acid and Sulbactam.

Latest development in antibiotics

In the last few years three new classes of antibiotics have been brought into clinical use. These new antibiotics are of the following three classes: cyclic lipopeptides (daptomycin), glycylcyclines (tigecycline), and oxazolidinones (linezolid). Tigecycline is a broad-spectrum antibiotic, while the two others are used for Gram-positive infections. These developments show promise as a means to counteract the bacterial resistance to existing antibiotics.
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