1. Copyright © 2015 Cengage Learning® 1 Chapter 17 Anti-Infective Drugs

2. Copyright © 2015 Cengage Learning® 2 Introduction Treatment of infection –Complicated by the great variety of medications available and their differing modes of action –First step: identify the causative organism and specific medication to which it is sensitive Culture and sensitivity (C&S) tests

3. Copyright © 2015 Cengage Learning® 3 Resistance Organisms may build up resistance to drugs and are therefore, no longer effective because of: –Frequent use –Incomplete treatment Anti-infective resistance is caused by many factors –Complex strategies needed to combat the problem

4. Copyright © 2015 Cengage Learning® 4 Resistance (cont’d.) Selection of anti-infective drugs –Infection site –Status of hepatic and/or renal function –Patient age –Pregnancy or lactation –Likelihood of organisms developing resistance –Known allergy to the anti-infective drug

5. Copyright © 2015 Cengage Learning® 5 Adverse Reactions Categories –Allergic hypersensitivity Over-response of the body to a specific substance –Direct toxicity Results in tissue damage –Indirect toxicity or superinfection Manifested as a new infection due to absence of normal flora in the intestines or mucous membranes

6. Copyright © 2015 Cengage Learning® 6 Vaccines/Immunizations Centers for Disease Control and Prevention (CDC) –Currently recommends routine vaccination Prevent 17 vaccine-preventable diseases that occur in infants, children, adolescents, or adults Information regarding vaccines and immunizations changes from time to time and requirements may vary by state, territory, or country

7. Copyright © 2015 Cengage Learning® 7 Aminoglycosides Treats many infections caused by: –Gram-negative bacteria (e.g., Escherichia coli and Pseudomonas) –Gram-positive bacteria (e.g., Staphylococcus aureus) Effective in short-term treatment of many serious infections –Septicemia (e.g., bacteria in bloodstream causing low blood pressure) when less toxic drugs are ineffective or contraindicated

8. Copyright © 2015 Cengage Learning® 8 Cephalosporins Semisynthetic beta-lactam antibiotic derivatives produced by a fungus –Related to penicillins Some patients allergic to penicillin are also allergic to cephalosporins Classified as first, second, third, or fourth, or fifth generation –According to organisms susceptible to their activity

9. Copyright © 2015 Cengage Learning® 9 Macrolides Treats many infections of the respiratory tract, skin conditions, or for some sexually transmitted infections –Considered among the least toxic antibiotics Preferred for treating susceptible organisms under conditions in which more toxic antibiotics might be dangerous

10. Copyright © 2015 Cengage Learning® 10 Penicillins Beta-lactam antibiotics produced from certain species of a fungus –Treats many streptococcal and some staphylococcal and meningococcal infections –Drug of choice for treatment of syphilis –Used prophylactically to prevent recurrences of rheumatic fever

11. Copyright © 2015 Cengage Learning® 11 Carbapenems Belong to the beta-lactam class of antibiotics –Have a very broad spectrum of activity against gram-negative and gram-positive organisms –Primary treatments include pneumonia, febrile neutropenia, intra-abdominal infections, diabetic foot infections, and significant polymicrobial infections

12. Copyright © 2015 Cengage Learning® 12 Quinolones For adult treatment of some infections of the urinary tract, sinuses, lower respiratory tract, GI tract, skin, bones, and joints, and in treating gonorrhea –Some organisms are showing increased resistance –Reserve for infections that require therapy with a fluoroquinolone

13. Copyright © 2015 Cengage Learning® 13 Tetracyclines Broad-spectrum antibiotics –Treats infections caused by rickettsia, chlamydia, or some uncommon bacteria –Some organisms are showing increasing resistance –Use only when other antibiotics are ineffective or contraindicated

14. Copyright © 2015 Cengage Learning® 14 Antifungals Treat specific susceptible fungal disease –Medications are quite different in action and purpose Amphotericin B –Administered IV for the treatment of severe systemic and potentially fatal infections caused by susceptible fungi, including Candida

15. Copyright © 2015 Cengage Learning® 15 Antifungals (cont’d.) Fluconazole –Works against many fungal pathogens, including most Candida, without the serious toxicity of amphotericin B Micafungin (Mycamine) –Given IV –Provides new treatment options against Candida and Aspergillus species

16. Copyright © 2015 Cengage Learning® 16 Antifungals (cont’d.) Nystatin –Structurally related to Amphotericin B –Orally treats oral cavity candidiasis –Also used as a fungicide in the topical treatment of skin and mucous membranes

17. Copyright © 2015 Cengage Learning® 17 Antituberculosis Agents Tuberculosis (TB) –Caused by a bacterium called Mycobacterium tuberculosis, which primarily attacks the lungs Antituberculosis agents are administered for two purposes –To treat latent or asymptomatic infection (no evidence of clinical disease) –For treatment of active clinical tuberculosis and to prevent relapse

18. Copyright © 2015 Cengage Learning® 18 Miscellaneous Anti-Infectives Clindamycin –Treats serious respiratory tract infections, septicemia, osteomyelitis, serious infections of the female pelvis caused by susceptible bacteria, and for Pneumocystis jirovecii pneumonia associated with AIDS –Prophylactic use in dental procedures for penicillin-allergic patients –May be a viable therapeutic option for community-acquired MRSA

19. Copyright © 2015 Cengage Learning® 19 Miscellaneous Anti-Infectives (cont’d.) Metronidazole (Flagyl) –Synthetic antibacterial and antiprotozoal agent –Effective against protozoa –One of the most effective drugs against anaerobic bacterial infections –Also useful in treating Crohn’s disease, antibiotic-associated diarrhea, rosacea, and H. pylori infection

20. Copyright © 2015 Cengage Learning® 20 Miscellaneous Anti-Infectives (cont’d.) Vancomycin –Structurally unrelated to other available antibiotics –IV vancomycin is used in the treatment of potentially life-threatening infections caused by susceptible organisms

21. Copyright © 2015 Cengage Learning® 21 Agents for VRE Linezolid (Zyvox) –Indicated for gram-positive infections –Approved for the treatment of bacterial pneumonia skin, skin structure infections, and MRSA and VRE infections –Effective in treating diabetic foot infections –Administered by IV infusion or orally

22. Copyright © 2015 Cengage Learning® 22 Sulfonamides Among the oldest anti-infectives –Increasing resistance of many bacteria has decreased the clinical usefulness of these agents Used most effectively in combinations with other drugs –Example: sulfamethoxazole and trimethoprim –Resistance develops more slowly

23. Copyright © 2015 Cengage Learning® 23 Urinary Anti-Infectives Urinary tract infection (UTI) –Symptomatic inflammatory response from the presence of microorganisms in the urinary tract –One of the most common bacterial infections for which patients seek treatment –First-line urinary anti-infectives for empiric treatment of uncomplicated lower UTI are sulfamethoxazole-trimethoprim and nitrofurantoin

24. Copyright © 2015 Cengage Learning® 24 Antivirals Acyclovir –Primarily treats herpes simplex, herpes zoster (shingles), and varicella zoster (chickenpox) infections Neuraminidase inhibitors –Indicated for the treatment of uncomplicated acute illness due to influenza types A and B

25. Copyright © 2015 Cengage Learning® 25 Antivirals (cont’d.) Ribavirin –Treats infants and young children with respiratory syncytial virus (RSV) infections via nasal and oral inhalation

26. Copyright © 2015 Cengage Learning® 26 Treatment of HIV/AIDS Infections Highly specialized field –Those actively practicing in that field must be updated frequently on the many new medications and frequently changing protocols Treatment of HIV infection –Consists of using highly active antiretroviral therapy (HAART) combinations of three or more antiretroviral (ARV) agents

27. Copyright © 2015 Cengage Learning® 27 Treatment of HIV/AIDS Infections (cont’d.) Antiretroviral protease inhibitors (PIs) –Block the activity of the HIV enzyme essential for viral replication late in the virus life cycle Nucleoside reverse transcriptase inhibitors (NRTIs) –Inhibit an enzyme responsible for viral replication early in the virus life cycle

28. Copyright © 2015 Cengage Learning® 28 Treatment of HIV/AIDS Infections (cont’d.) Non-nucleoside reverse transcriptase inhibitors (NNRTIs) –Inhibit an enzyme responsible for viral replication early in the viral life cycle Fusion inhibitors (FIs) –Block entry of HIV into cells, which may keep the virus from reproducing

29. Copyright © 2015 Cengage Learning® 29 Treatment of HIV/AIDS Infections (cont’d.) CCR5 antagonists –Block a co-receptor required for HIV entry into human cells Integrase inhibitor –Raltegravir (Isentress): first ARV designed to slow the advancement of HIV infection by blocking the enzyme needed for viral replication

30. Copyright © 2015 Cengage Learning® 30 HIV Information and Resources Sources of current recommendations for clinical use of antiretrovirals (ARVs) –Department of Health and Human Services –Florida/Caribbean Aids Education and Training Center –AETC National Resource Center Drug Interactions –Johns Hopkins HIV Guide –National HIV Telephone Consultation Service –University of California, San Francisco