Antibiotics

Definition

Antibiotics are drugs derived from molds or bacteria that inhibit the growth of other microorganisms. Even modern antibiotics that are chemically modified can be traced back to a substance originally found in a microorganism.

Description

A large number of antibiotics are available. They are classified by their chemical structure since drugs with similar chemical structures tend to have similar actions. Based on clinical experience, physicians may know that some types of infection normally respond to specific antibiotics, but if the infection fails to respond, or recurs, it may be necessary to do culture and sensitivity testing. Microorganisms develop resistance to antibiotics, and so there is no assurance that an antibiotic will retain its effectiveness against some types of infection.

Patterns of bacterial resistance also depend on the environment where the infection is acquired. In hospitals, where antibiotics are widely used, microorganisms are usually more resistant than those found outside the hospital. Infections developed by hospitalized patients often require different treatment from infections developed outside the hospital (community acquired).

Penicillins

• Penicillin G
• Penicillin V
• Nafcillin
• Oxacillin

• Ampicillin

  Antibiotics

  Brand name	Generic name
  (Illustration by GGS Information Services. Cengage Learning, Gale)
  Aminoglycosides
  Amikin	amikacin
  AK-Tob, Tobi, Tobrex	tobramycin
  Capastat Sulfate	capreomycin sulfate
  Garamycin, Gentak, Pred-G	gentamicin
  Kantrex	kanamycin
  Netromycin	netilmicin
  Carbapenems
  Invanz	ertapenem
  Merrem I.V.	meropenem
  Primaxin	imipenem/cilastatin
  Cephalosporins
  Ancef	cefazolin
  Ceclor	cefaclor
  Cedax	ceftibuten
  Ceftin, Zinacef	cefuroxime
  Cefzil	cefprozil
  Duricef	cefadroxil
  Fortaz, Tazicef	ceftazidime
  Keflex	cephalexin
  Mefoxin	cefoxitin
  Omnicef	cefdinir
  Rocephin	ceftriaxone
  Spectracef	cefditoren
  Suprax	cefixime
  Vantin	cefpodoxime
  Macrolides
  Biaxin, Biaxin XL	clarithromycin
  ERYC, Ery-Tab, EryDerm, EryGel, PCE	erythromycin
  Zithromax	azithromycin
  Penicillins
  Amoxil, Trimox	amoxicillin
  Bactocill	oxacillin
  Dicloxacillin Sodium	dicloxacillin sodium
  Pfizerpen	penicillin G
  Principen	ampicillin
  Timentin	ticarcillin (and clavulanate)
  Unipen	nafcillin
  V-Cillin K, Veetids	penicillin V
  Zosyn	piperacillin (and tazobactam)
  Polypeptides
  Baciim, Baci-Rx	bacitracin
  Coly-Mycin S	colistin sulfate
  Polymyxin B Sulfate	polymyxin b sulfate
  Quinolones
  Avelox, Vigamox	moxifloxacin hydrochloride
  Ciloxan, Cipro	ciprofloxacin hydrochloride
  Levaquin, Quixin	levofloxacin
  Maxaquin	lomefloxacin hydrochloride
  Noroxin	norfloxacin
  Tequin, Zymar	gatifloxacin
  Sulfonamides
  Azulfidine	sulfasalazine
  Bleph-10, Bleph-30, Cetamide, Isopto Cetamide, Ocusulf-10, Sulf-10	sulfacetamide sodium
  Gantanol	sulfamethoxazole
  Gantrisin	sulfisoxazole
  Silvadene	silver sulfadiazine
  Sulfamylon	mafenide acetate
  Thiosulfil Forte	sulfamethizole
  Tetracyclines
  Declomycin	demeclocycline
  Doryx, Monodox, Vibramycin, Vibra-Tabs	doxycycline hyclate
  Dynacin, Minocin	minocycline hydrochloride
  Sumycin	tetracycline hydrochloride
  Terramycin	oxytetracycline
  Miscellaneous
  Chloramphenicol	chloramphenicol
  Cleocin, Cleocin T, Clinda-Derm, Clindagel, Clindets, Clindesse	clindamycin
  Coly-Mycin M	colistimethate
  Flagyl, Flagyl ER, Flagyl I.V., Noritate, Metrog	metronidazole
  Furadantin, Macrobid	nitrofurantoin
  Monurol	fosfomycin tromethamine
  Myambutol	ethambutol
  Nydrazid	isoniazid
  Pyrazinamide	pyrazinamide
  Synercid	quinupristin/dalfopristin
  Trobicin	spectinomycin hydrochloride
  Vancocin	vancomycin hydrochloride
  Combination products
  Cortisporin, DexaSporin, Maxitrol, Neosporin Ophthalmic	bacitracin, neomycin, and polymyxin b sulfate
  Duac	clindamycin and benzoyl peroxide
  Helidac	tetracycline hydrochloride, metronidazole, and bismuth subsalicylate
  Prevpac	clarithromycin, amoxicillin, and lansoprazole
  Poly-Pred	neomycin, polymyxin b sulfate, and prednisolone
  Rifamate	isoniazid and rifampin
  Rifater	isoniazid, rifampin, and pyrazinamide
  TobraDex	Dexamethasone and tobramycin

  Amoxicillin

• Carbenicillin
• Piperacillin
• Ticarcillin

Penicillin was first discovered by Scottish researcher Sir Alexander Fleming (1881–1955) in 1928, and first used in treatment in the 1940s. Penicillin G is the original penicillin, and is still clinically valuable. Penicillin V is a chemical modification of penicillin with similar activity, but it is more stable in the acidic environment of the digestive tract. Penicillins G and V are effective against anaerobic bacteria (bacteria that live in the absence of air). Since anaerobic bacteria are common in the oral cavity, these two penicillins are widely used in dentistry.

Penicillins are bactericidal, meaning that they kill bacteria. They block the ability of bacteria to develop a cell wall. As a result, penicillins are most effective against bacteria that are actively multiplying.

Nafcillin and oxacillin are called penicillinase resistant penicillins because they are relatively resistant to the enzyme penicillinase produced by some bacteria. Penicillinase inactivates penicillin. The first penicillin in this class was methicillin. Although methicillin is no longer used, bacteria that have developed a resistance to this class of drugs are still referred to as methicillin resistant. The term methicillin-resistant Staphylococcus aureus (MRSA) applies to a strain of bacteria resistant to all penicillins.

Ampicillin and amoxicillin are aminopenicillins, which are effective against a wider range of bacteria than the original penicillins. Aminopenicillins are sensitive to penicillinase, but they can be combined with penicillinase inhibitors such as potassium clavulanate or sulbactam. The resulting combination is effective against penicillinase producing strains of bacteria.

Carbenicillin, piperacillin and ticarcillin are extended spectrum penicillins, and may be effective against some bacteria that are resistant to other penicillins.

Cephalosporins

Cephalosporins are chemically related to penicillins in that they have the same central ring structure, called the beta lactam ring. Some drugs in this group are not cephalosporins technically, but are considered together because they have similar structures, uses and activity. Cephalosporins are usually grouped by generation.

First generation cephalosporins are generally effective against simple infections of the skin and soft tissues. Cefazolin is widely used before surgery to prevent development of infections. Additional first generation cephalosporins are:

• Cefadroxil
• Cephalexin
• Cephradine

Second generation cephalosporins and the closely related cephamycins have a broader spectrum than the first generation drugs, and may be useful when an infection is caused by more than one organism. Cefoxitin and cefotetan are effective against anaerobic organisms, and may help treat infections of the intestines, decubitus ulcers or diabetic foot ulcers. Other second generation cephalosporins are:

• Cefaclor
• Cefprozil
• Cefuroxime

Third generation cephalosporins have a broader spectrum of action than the second generation drugs, and usually have better penetration into the central nervous system, making them useful for treatment of meningitis . It is often necessary to use third generation cephalosporins in combination with other antibiotics. Ceftazidime and cefoperazone are active against Pseudomonas aeruginosa, which is often resistant to other antibiotics. Some drugs in this group have relatively long durations of action and may require only one dose each day. Since these drugs are given intravenously, the drugs requiring fewer doses are good choices for home care . Third generation cephalosporins also include:

• Cefdinir
• Cefditoren
• Cefixime
• Cefotaxime
• Cefpodoxime
• Ceftibuten
• Ceftozoxime
• Ceftriaxone

Cefepime is sometimes called a fourth generation cephalosporin, but it is essentially the same as the third generation group.

Aminoglycosides

• Amikacin
• Gentamicin
• Neomycin
• Streptomycin
• Tobramycin

Streptomycin, the first of the aminoglycoside antibiotics, was isolated from soil bacteria by Russian American microbiologist Selman Waksman (1888–1973) in 1943. Drugs in this class are bactericidal and act by binding to proteins inside bacterial cells. These drugs are rarely used alone except for treating plague and tularemia. They are moe commonly used in hospitals in combination with beta-lactam antibiotics, for treatment of resistant infections. Even for that purpose, bacterial resistance has developed, leading some experts to advocate for replacing the aminoglycoside with a flouroquinolone in combination therapy. Amikacin, gentamicin and tobramycin are usually used in hospitals, and the selection is based on experience with the bacterial resistance patterns at the institution.

Streptomycin is used in combination with other drugs for treatment of tuberculosis . Neomycin and kanamycin are toxic, making their use limited. Neomycin is poorly absorbed through skin or mucous membranes, so it can be safely used as eye drops, ear drops, or for bowel cleansing before surgery. When swallowed, neomycin kills intestinal bacteria, but is not absorbed in large enough amounts to have any systemic effect.

Tetracyclines

• Tetracycline
• Demeclocycline
• Doxycycline
• Minocycline

There is some evidence that tetracycline was a byproduct of brewing and baking in ancient Egypt and that the antibacterial effects of beer were recognized and applied medicinally at that time. Several variants on tetracycline, including chlortetracycline and oxy-tetracycline, were discovered around the same period in the late 1940s. They all were found to have similar chemical structures and actions. Tetracyclines are bacteriostatic drugs—drugs that do not kill bacteria, but inhibit growth so that the normal immune response can destroy the pathogens. Tetracyclines are broad spectrum antibiotics, effective against a wider range of bacterial pathogens than any earlier antibiotics. Bacteriocidal drugs are generally preferred when available, but tetracycline and its derivatives are invaluable for treatment of Rocky Mountain Spotted Fever, Q Fever, chancroid and plague.

The tetracyclines have a broad spectrum, low toxicity, and good penetration into the skin, so they have been widely used for treatment of acne. Doxycycline has been recommended for prevention of traveler's diarrhea and some strains of malaria.

Flouroquinolones

• Ciprofloxacin
• Gatifloxacin
• Gemifloxacin
• Levofloxacin
• Moxifloxacin

• Norfloxacin

  Ofloxacin

• Trovafloxacin

Flouroquinolones are a newer group of antibiotics, and are relatively uniform in their actions and uses. They may be used in urinary tract infections, bacterial prostatitis, and most forms of infectious diarrhea. Ciprofloxacin has been useful in combination with a beta-lactam antibiotic against some resistant hospital acquired infections. It was also recommended for prevention against anthrax during the 2001 bio-terrorism alerts.

Flouroquinolones have been a major advance in antibiotic therapy, but their widespread use has resulted in bacterial resistance to some older members of this class of drugs.

Macrolides

• Azithromycin
• Clarithromycin
• Erythromycin
• Telithromycin

Erythromycin is used as an alternative to penicillin for patients who are allergic to the penicillin group. Although erythromycin is very similar in action and uses to penicillin G, it causes more stomach distress, and severe vein irritation when injected. Erythromycin is applied to the skin for treatment of acne.

Zithromycin and clarithromycin are relatively new, are more effective against many infections of the respiratory tract, and have a high degree of tolerability. They are particularly useful against Hemophilus influenzae and Mycobacterium avium complex. They are also useful against Legionnaire's Disease and other types of lung infections. Azithromycin is used for infections of the urethra and the cervix.

Telithromycin is a ketolide antibiotic, but is closely related to the macrolides. The unique chemical structure of this antibiotic makes it a broad spectrum antibiotic effective against penicillin- and macrolide-resistant pathogens. Telithromycin is primarily used to treat respiratory infections. The U.S. Food and Drug Administration (FDA) has issued warnings, and reduced the number of conditions telithromycin is approved to treat because of its toxicity. However, it remains useful for infections that are resistant to other antibiotics.

Other antibiotics

A large number of other antibiotics exist, but are less widely used than those just described.

Chloramphenicol is a broad spectrum antibiotic that is no longer considered the drug of choice for any infection, but is still used for serious infections that are resistant to other antibiotics.

Clindamycin has a spectrum of action similar to that of erythromycin, but is more useful in treatment of anaerobic infections.

Recommended dosage

The usual recommended doses for antibiotics may not apply to elderly patients due to unique problems typical for this age group. There is a normal age-related decline in kidney function and since most antibiotics are eliminated through the kidneys, lower doses may be necessary, particularly for those drugs that may themselves impair renal function. At the same time, because of age related declines in immune system function, higher blood levels of antibiotics may be required in elderly patients. Although some drugs have been studied in an elderly population and specific guidelines for dosing are available, these recommendations may be altered by the presence of coexisting diseases, and use of other medications at the same time. Whenever possible, infections in the elderly should be treated by physicians familiar with the specific needs of geriatric patients.

Precautions

Antibiotics may have special risks. The physician and pharmacist should discuss potential side effects and drug interactions with the patient. It is important that the patient tell their physician all medications they are using, both prescription and over-the-counter, as well as herbal preparations and other drugs.

Any side effects or adverse reactions should be reported to the physician immediately. Elderly patients may need guidance regarding what is and what is not a side effect.

In some cases, drug absorption can vary with the type of the food consumed. Patients should review the antibiotic label to determine if it should be taken with meals or on an empty stomach. Unless otherwise directed, store antibiotics in a cool, dry place. Do not store antibiotics in a medicine cabinet that may become steamy due to showering, or in a refrigerator.

Antibiotics have a limited shelf-life, and work only on specific organisms. It may be tempting to save extra doses and take them the next time there is evidence of an infection, but this is not safe because the drug may not be the right choice for the new infection, or it may have expired and will no longer be effective. Rarely, some antibiotics cause more severe allergic reactions when the drug passes its expiration date.

Side effects

All antibiotics have some side effects and adverse effects. The physician or pharmacist should discuss these with the patient when prescribing antibiotic medications.

Almost all antibiotics can cause diarrhea and hairy tongue. This occurs when the antibiotic kills some of the normal bacteria in the mouth and intestinal tract, leaving an overgrowth of resistant molds and fungi. The problem is more common with broad spectrum antibiotics, but has been reported with narrow spectrum drugs. Ampicillin causes diarrhea more frequently than does amoxicillin, although this advantage is seen more often in children than in adults.

Allergic reactions can be a serious problem with all antibiotics, but are particularly noted with the penicillins. Patients allergic to penicillin may also be allergic to cephalosporins. Because of the importance of these two classes of drugs in both treatment and prevention of infection, patients should describe all adverse reactions to penicillin in great detail. It is important to distinguish between a true allergic reaction, which is reason not to use these drugs, and a side effect such as upset stomach or mild dizziness .

Tetracyclines can cause photosensitization in which the skin becomes extra sensitive to sunlight. Demeclocycline is more prone to cause this problem than other tetracyclines. Persons taking tetracyclines should avoid excessive sun exposure. Some flour-oquinolones cause photosensitization, even with the use of sunblocks, or when light passes through glass.

Ruptures of the shoulder, hand, and Achilles tendons requiring surgical repair or resulting in prolonged disability have been reported with fluoroquinolones. Patients taking these drugs should report joint pain to their physician immediately. If tendon rupture is suspected, patients should avoid activity until a formal diagnosis has been made.

Telithromycin has been associated with severe liver toxicity.

Other potential adverse reactions to antibiotics include stomach upset, nausea, vomiting, nervousness, sleep disturbances, nervousness, anxiety and other problems. Rarely, antibiotics can affect critical organs including the liver and kidneys or cause convulsions and coma .

Interactions

The following interactions are of particular interest to seniors. Other interactions may also occur.

All antibiotics may increase the effects of warfarin, a medication used to prevent blood clots . Patients taking warfarin should have additional monitoring while taking antibiotics. Penicillins may interact with heparin to prolong bleeding time. Beta blockers may increase the risk of allergic reactions to penicillins.

QUESTIONS TO ASK YOUR PHARMACIST

• Is there a generic form of the name brand drug that was prescribed?
• Should this medication be taken with or without food?
• What adverse effects are most likely to occur? What are their symptoms?
• How should this medication be stored?
• Are there other medications or alternative treatments that should be avoided while I am taking this antibiotic?

Cefoperazone, cefazolin, cefmetazole and cefotetan have been reported to cause alcohol intolerance. Alcohol in any form should be avoided for 72 hours after receiving any of these drugs. Cefdinir should not be taken with iron supplements or foods rich in iron since this reduces their antibiotic effect. All cephalosporins should be used with caution in patients taking loop diuretics such as furosemide, since this may increase the risk of kidney damage. Do not take cephalosporins at the same time as antacids or histamine receptor blocking agents because they may reduce the effectiveness of the antibiotic.

Macrolides should not be taken with antacids. Clarithromyc and erythromycin may increase the effects of some anxiolytic drugs, including diazepam, alprazolam, triazolam and others. This may lead to unwanted sedation.

Tetracyclines should be taken with water, preferably on an empty stomach. They can interact with minerals such as calcium and sodium in dairy products, antacids and supplements. Combining these minerals with tetracycline results in some or all of their anti-infective activity being lost.

Caregiver concerns

Caregivers should discuss the selection of antibiotic with the physician. The caregiver can ensure the physician is aware of all medications, including over-the-counter drugs that the patient is taking.

To help with cost concerns, caregivers can ask if a generic drug is available for the brand name drug prescribed.

KEY TERMS

anaerobic —Not requiring oxygen. Anaerobic bacteria are commonly found in the mouth, intestines and vaginal area.

antibiotic —A chemical substance produced by a microorganism that kills or stops the growth of other microorganisms. The term includes antibiotics chemically modified from their original form, such as the semi-synthetic penicillins, but not the agents that come from sources other than microorganisms.

bacteria —The plural of bacterium; unicellular organisms that have a cell wall and multiply by cell fission. Some bacteria cause disease, while others are beneficial to human health. Still other have importance in commercial applications.

decubitus —This term refers to the position of a patient in a bed, but is rarely used that way. In common usage it applies to a bedsore; skin breakdown caused by continued pressure.

enzyme —An organic catalyst; a substance produced by an organism that acts as a catalyst to promote a chemical reaction.

fungus —A group of plants that lack chlorophyll and reproduce by spores.

infection —Invasion of the body by organisms that are able to cause disease.

mold —A term referring to both fungi and yeasts.

rupture —A tear in an organ or other tissue.

tendon —The connective tissue that holds muscle to a bone.

Most importantly, caregivers should be familiar with major adverse effects that the drug may cause, both in terms of severity and frequency. When reporting an adverse effect, describe it in as much detail as possible. Do not use the words “allergy” or “allergic” unless the reaction has been confirmed as a true immune response.

Resources

BOOKS

The Dispensatory of the United States of America, 25th edition, edited by A. Osol and G. Farrar. Philadelphia: J. B. Lippincott Co, 1955.

Martindale the Extra Pharmacopoeia, 30th edition, edited by J. Reynild. London: The Pharmaceutical Press, 1993.

PERIODICALS

Esposito, S., et al. “Antibiotic Resistance in Long-term Care Facilities.” New Microbiology 30, no. 3 (July 2007): 326–31.

Faulkner, C. M., H. L. Cox, and J. C. Williamson. “Unique Aspects of Antimicrobial Use in Older Adults.” Clinical Infectious Diseases 40, no. 7 (April 1, 2005): 997–1004.

Herring, A. R., and J. C. Williamson. “Principles of Anti-microbial Use in Older Adults.” Clinical Geriatric Medicine 23, no. 3 (August 2007): 481–97.

Niederman, M. S., and V. Brito. “Pneumonia in the Older Patient.” Clinics in Chest Medicine 28, no. 4 (December 2007): 751–71, vi.

Noreddin, A. M., and V. Haynes. “Use of Pharmacodynamic Principles to Optimize Dosage Regimens for Antibacterial Agents in the Elderly.” Drugs & Aging 24, no. 4 (2007): 275–92.

Razavi, B., A. Apisarnthanarak, and L. M. Mundy. “Clostridium difficile: Emergence of Hypervirulence and Fluoroquinolone Resistance.” Infection 35, no. 5 (October 2007): 300–7.

Trinh, C., and K. Prabhakar. “Diarrheal Diseases in the Elderly.” Clinical Geriatric Medicine 23, no. 4 (November 2007): 833–56, vii.

Woodmansey, E. J. “Intestinal Bacteria and Ageing.” Journal of Applied Microbiology 102, no. 5 (May 2007):1178–86.

OTHER

Information for Consumers. U.S. Food and Drug Administration: Center for Drug Evaluation and Research. [cited April 10, 2008]. http://www.fda.gov/cder/info/consumer.htm.

Rainbow, J. et al. “Emergence of Fluoroquinolone-Resistant Neisseria meningitides—Minnesota and North Dakota, 2007-2008.

” MMWR Weekly February 22, 2008 [cited April 10, 2008]. Centers for Disease Control. http://www.cdc.gov/mmwr/preview/mmwrhtml/mm5707a2.htm.

Sam Uretsky PharmD