Introduction

Antibiotics are a complex group of organic chemicals produced by microorganisms that have a detrimental effect on other organisms.¹ The sulphonamides are synthetic organic materials and, in the true sense of the word, are classified as antibacterials rather than antibiotics. All antibiotics are bacteriostatic, which means that at suitable concentrations they inhibit bacterial growth, and some antibiotics are bactericidal, which means that they are able to destroy bacteria when conditions are suitable.¹ Antibacterials are one of the most commonly used groups of drugs in veterinary medicine and the development of bacterial resistance to these drugs is of grave concern to both animal and human health. In this presentation the groups of antibiotics will be discussed and their rational use will be addressed.

Antibiotic Groups and Mechanism of Action

Antibiotics can be classified according to their activity against gram-negative and/or gram-positive bacteria, as well as activity against aerobic and anaerobic bacteria. They may also be classified as bactericidal or bacteriostatic drugs. Antibiotics act against bacteria by interfering with either cell wall synthesis, nucleic acid synthesis, or protein synthesis.

 Penicillin

 Bactericidal

 Interferes with cell wall synthesis

 Good gram-positive activity with some gram-negative activity of the aminopenicillins

 Combined with clavulanic acid to inhibit beta-lactamase

 Cephalosporins

 Bactericidal

 Interferes with cell wall synthesis

 Good gram-positive activity with increasing gram-negative activity with second- and third-generation cephalosporins

 Fluoroquinolones

 Bacteriostatic

 Inhibit DNA gyrase

 Dose-dependent bactericidal activity

 Broad spectrum

 Aminoglycosides

 Bactericidal

 Inhibits protein synthesis

 Gram-negative activity

 Ototoxicity and nephrotoxicity

 Tetracyclines

 Bacteriostatic

 Inhibit bacterial protein synthesis

 Effective against Rickettsia, Mycoplasma and Chlamydia

 Macrolides

 Bacteriostatic

 Inhibits protein synthesis

 Activity against gram-positive aerobic and anaerobic bacteria

 Activity against Mycoplasma and Chlamydia

 Examples are azithromycin, lincomycin, and clindamycin

 Metronidazole

 Bactericidal

 Effective against anaerobes

 CNS toxicity

Selecting an Antibiotic

Ideally, before starting antibiotic therapy bacterial culture and sensitivity testing would be required. This is not always practical and often empirical antibiotic therapy is used without prior knowledge of the bacteria or the susceptibility profile. When selecting an antibiotic, take into account factors such as the site of infection, status of the immune system, concurrent diseases, age of the animal, and physiological status of the patient.² The organ system involved often provides a good idea as to the antibiotic choice. Skin infections in dogs and cats are often caused by Staphylococcus intermedius or S. aureus. Effective antibiotics could include amoxicillin + clavulanic acid combination, cephalosporins, or enrofloxacin. Treatment time for skin infection should be anything from 3 weeks for superficial pyoderma and up to 8 weeks for deep pyoderma.² Urinary tract infections are often caused by E. coli and drugs that reach high concentrations in the urine and the prostate are enrofloxacin and trimethoprim-sulfonamides.

The agar-disk diffusion test is the most familiar test used for measuring bacterial susceptibility to antimicrobials.³ This test measures the inhibition of bacterial growth against a concentration of antimicrobial that diffuses from an antibiotic-infused paper disc placed on the agar.³ The zone size can be directly correlated to the minimum inhibitory concentration (MIC). There are limitations to in vitro antibacterial susceptibility testing. They do not take into account tissue concentration which may differ from plasma concentrations. They also do not take into account synergistic antibiotic combinations. Local factors such as blood perfusion, pus, and necrotic debris may also affect antibiotic activity.³

The MIC is the minimum concentration of an antibiotic in vitro that inhibits bacterial growth. This is considered the pharmacodynamic measurement. The relationship of MIC to clinical outcome has been correlated to certain variables such as peak plasma concentration and the area of the plasma concentration versus the time curve (AUC) and the length of time plasma concentration is above the MIC over a 24-hour period.³ These are called the pharmacokinetic measurements. The pharmacodynamic/pharmacokinetic measurements can be used to predict clinical outcomes. For bacteriostatic drugs time above the MIC at the site of infection is the most important marker. Bactericidal drugs may be time dependent or concentration dependent. Time-dependent drugs include the penicillins and cephalosporins and the concentrations of these drugs should be kept above the MIC throughout most of the dosage intervals. Thus for more serious infections the use of a potentiated aminopenicillin 3–6 times daily will be more effective. Concentration-dependent drugs include the aminoglycosides such as gentamicin and amikacin. Here the peak plasma concentration above the MIC is important and the plasma concentration can fall below the MIC for 8–12 hours over a day and still effect a cure. Once-a-day dosage can be effective and safe. The fluoroquinolone antibiotics also rely on a high peak plasma concentration to MIC ratio. Area under the curve to MIC ratio can also be used.

Antibiotic Resistance

Increasing bacterial resistance to antibiotic therapy is of major concern to human health and to a lesser extent to animal health. The overzealous and inappropriate use of antibiotics leads to increasing bacterial resistance resulting in life-threatening bacterial infections. Methicillin-resistant Staphylococcus aureus (MRSA) has reached alarming rates in the community and in hospitals. There are now reports of MRSA in our veterinary patients.⁴ The most common resistant gram-negative bacilli encountered in small animal veterinary practice are Escherichia coli. Another important gram-negative bacterium that is non enteric is Pseudomonas aeruginosa. It tends to be resistant to many antibiotics because they fail to penetrate the organisms' outer membrane and they produce beta-lactamase.

References

1.  Brander GC, Pugh DM. Veterinary Applied Pharmacology and Therapeutics. 3rd ed. London, UK: Harcourt Publishers; 1977.

2.  Vaden SL, Papich MG. Empiric antibiotic therapy. In: Kirk's Current Veterinary Therapy XII. Philadelphia, PA: WB Saunders; 1995: 276–280.

3.  Papich MG. Antimicrobial drugs. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine. Chapter 74. 5th ed. Philadelphia, PA: WB Saunders; 2000: 301–307.

4.  Papich MG. Antibacterial drug therapy. In: Ettinger SJ, Feldman EC, eds. Textbook of Veterinary Internal Medicine. Chapter 154. 7th ed. St. Louis, MO: Saunders Elsevier; 2010: 589–595.