1. CHAPTER 41 Antibacterial Agents

2. Bacterial Morphology • Bacteria are classified by bacterial shape and colony arrangement • Cocci are spherical in shape and usually arranged in pairs (diplo), chains (strepto), or clusters (staphylo) • Bacilli are rod-like in shape • Spirilla are curved and rod-like in shape • See P 496

3. Gram Staining • Gram staining classification is based on ability of the bacterial membrane to stain either red or blue • Bacteria that take up the red stain are classified as gram positive, Gm(+) • Bacteria that take up the blue stain are classified as gram negative, Gm(-) • Gm(-) bacteria have an additional outer lipopolysaccharide membrane layer (endotoxin) that is toxic and that can produce endotoxic shock

4. Antibacterial Chemotherapy • Defined as the use of drugs to kill or inhibit the growth of infectious bacteria • Bactericidal drugs kill the bacteria • Bacteriostatic drugs inhibit the growth of bacteria and body defenses and immune mechanisms are required to rid the body of infecting bacteria

6. Antibacterial Spectrum • Refers to the range of bacteria that are killed or inhibited by any antibacterial drug • Narrow spectrum drugs are effective against a limited number of different bacterial species • Broad spectrum drugs are effective against a wide range of different bacterial species

7. Bacterial Resistance • Bacteria have the ability to produce proteins that help them resist antimicrobial drug actions • Some bacteria produce beta-lactamase enzymes that inactivate penicillins and cephalosporins • Some bacteria produce proteins that prevent drugs from penetrating the bacterial membrane or proteins that remove the drugs once they have passed through the bacterial membrane • When bacterial resistance occurs other drugs must be used to treat the infection

8. Six families of antibacterial drugs • 1. penicillins • 2. cephalosporins • 3. tetracyclines • 4. aminoglycosides • 5. macrolides • 6. fluoroquinolones • 7. other

9. Penicillins • Bacteriocidal drugs that inhibit cell wall synthesis • 1st generation drugs have a narrow spectrum and indicated mostly for Gm(+) infections • 2nd generation drugs have a wider spectrum that includes most common Gm(+) / Gm(-) bacterial infections • 3rd and 4th generation drugs have a broad spectrum and are effective against most Gm(-) bacteria

10. Penicillins • 1st generation • Penicillin G - IM, IV • Penicillin V – PO • 2nd generation • Methicillin (Staphcillin) • 3rd generation • Carbenicillin (Geocillin) • 4th generation • Piperacillin (Pipracil)

11. Cephalosporins • Bacteriocidal drugs that inhibit cell wall synthesis • 1st generation drugs are effective against most common Gm(+) and Gm(-) bacteria • 2nd, 3rd, and 4th generation cephalosporins have increasing activity against Gm(-) bacteria • Cephalosporins are the drugs of choice for infections caused by Klebsiella pneumoniae • Cephalosporins are more resistant to inactivating beta-lactamase enzymes than penicillins

12. Cephalosporins • 1st generation • Cephalexin (Keflex) – PO • 2nd generation • Cefaclor (Ceclor) – PO • 3rd generation • Ceftriaxone (Rocephin) – IM,IV • 4th generation • Cefepime (Maxipime) – IM,IV

13. Adverse Effects Common to Penicillins and Cephalosporins • Minor GI disturbances and diarrhea • Hypersensitivity or allergic reactions that include delayed skin reactions or immediate anaphylactic reactions • Higher dosages may cause bleeding problems • Higher dosages may cause CNS disturbances and possible seizures

14. Aminoglycosides • Classified as broad spectrum antibiotics • Bacteriocidal drugs that inhibit bacterial protein synthesis • Administered IM or IV for systemic effects • Usually the drugs of choice for serious gram negative infections • Nephrotoxicity and ototoxicity are the most serious adverse effects

15. Aminoglycosides • Gentamicin (Garamycin) • Kanamycin (Kantrex) • Streptomycin • IM or IV only • Often used in combination therapy

16. Tetracyclines • Basteriostatic drugs that inhibit bacterial protein synthesis • Administered orally, but not with dairy or antacid products • Doxycycline (Vibramycin) is the most widely used tetracycline and usually taken once per day • Adverse effects include GI disturbances, rash, and photosensitivity • Tetracyclines are contraindicated during pregnancy, nursing, and in children < age 8

17. Sulfonamides • Bacteriostatic drugs that inhibit bacterial folic acid synthesis • Sulfonamides (Gantricin) are mainly indicated for treatment of urinary tract infections • Trimethoprim/sulfamethoxazole (Bactrim, Septra) has a broad antibacterial spectrum and many indications • Adverse effects include rash, allergy, blood disorders, and renal tubule damage

18. Macrolide Antibiotics • Bacteriostatic drugs that inhibit bacterial protein synthesis, effective with oral administration • Erythromycin often used in penicillin allergic patients for minor ear and throat infections • Azithromycin (Zithromax) and clarithromycin (Biaxin)have a broader antibacterial spectrum and clinical uses • Adverse effects include heartburn, rashes, and GI disturbances

19. Fluroquinolones • Bactericidal drugs that inhibit an enzyme essential to the function of bacterial DNA • Administered orally • Indicated for a wide variety of urinary, soft tissue, bone, and respiratory infections • Adverse effects include GI disturbances, rash, photosensitivity, and joint pain • Contraindicated in pregnancy and young children

20. Fluroquinolones • Ciprofloxacin (Cipro) • Levofloxacin (Levaquin) • Given PO - often used for throat infection& pneumonea • May cause tendon rupture

21. Miscellaneous Antimicrobials • Chloramphenicol (Chloromycetin) is reserved for serious infections such as typhoid fever and meningitis • Clindamycin (Cleocin) indicated for Gm(+) and anaerobic infections – may cause C dif colitis • Vancomycin indicated for resistant Gm(+) staphylococcal infections (MERSA) • Quinupristin-dalfopristin and linezolid indicated for Gm(+) infections resistant to vancomycin – rarely used

22. Drugs Used to Treat Tuberculosis • Tuberculosis requires prolonged treatment with multiple drugs, usually 3 or 4 different drugs • The first line drug regimen includes isoniazid, rifampin, pyrazinamide, and ethambutol • After 2–4 months of treatment ethambutol and pyrazinamide are usually eliminated • Isoniazid and rifampin therapy is continued for 6–12 months • Drug resistance is a major problem