Chapter 14. Antimicrobial Agents. Mosby items and derived items 2008, 2002 by Mosby, Inc., an affiliate of Elsevier Inc.
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1 Chapter 14 Antimicrobial Agents
2 Principles of Antimicrobial Therapy Identification of the pathogen Gram stain Acid-fast stain Enzyme-linked immunosorbent assay (ELISA)
3 Principles of Antimicrobial Therapy (cont d) Susceptibility testing and resistance Kirby-Bauer disk diffusion E-test Minimal inhibitory concentration (MIC) Minimal bactericidal concentration (MBC)
4 Principles of Antimicrobial Therapy Host factors (cont d) Impaired immune function Age Liver and kidney function Stomach ph Pregnancy Could drug harm fetus?
5 Principles of Antimicrobial Therapy Pharmacodynamics (cont d) Measured in vitro by time-kill studies Concentration-dependent effect Time-dependent effect (concentration independent) Postantibiotic effect
6 Principles of Antimicrobial Therapy (cont d) Antimicrobial combinations May need to cover broad spectrum of organisms initially Regimen may be narrowed once organism identified Are drugs synergistic or antagonistic?
7 Principles of Antimicrobial Therapy (cont d) Monitoring response to therapy Fever? WBC? Cultures still positive? Symptoms resolved? Drug toxicity?
8 Antibiotics Penicillins Inhibit cell wall synthesis Activate endogenous autolytic system in bacteria
9 Antibiotics (cont d) Natural penicillins Penicillinase-resistant penicillins Aminopenicillins Carboxypenicillins Ureidopenicillins β-lactam and β-lactamase inhibitor combinations
10 Antibiotics (cont d) Adverse reactions and precautions for the penicillins Hypersensitivity (most common) Hematological reactions Gastrointestinal disturbances CNS toxicity
11 Antibiotics (cont d) Cephalosporins Inhibit bacterial cell wall synthesis
12 Clinical uses Antibiotics (cont d) First-generation cephalosporins Wide variety of gram-positive organisms Second-generation cephalosporins Gram-positive and some gram-negative organisms Third-generation cephalosporins Active against most gram-negative organisms Fourth-generation cephalosporins Extended gram-positive and gram-negative coverage
13 Antibiotics (cont d) Adverse reactions and precautions for cephalosporins Hypersensitivity (1 to 3%) Minor gastrointestinal complaints Hypoprothrombinemia Flushing Nausea Thirst Palpitations Chest pain Vertigo Death (in some cases)
14 Antibiotics (cont d) Carbapenems Mechanisms of action Similar to other β-lactams Inhibit cell wall synthesis Bactericidal
15 Antibiotics (cont d) Pseudomonas aeruginosa (except ertapenem), gramnegative bacilli, most anaerobes, gram-positive organisms Low incidence of adverse reactions Seizures in patients with decreased renal function
16 Antibiotics (cont d) Monobactams (aztreonam) Similar to other β-lactams Gram-negative aerobic bacilli Well tolerated Rare: Rash, anaphylaxis
17 Antibiotics (cont d) Aminoglycosides Inhibit RNA translation Destabilize cell wall Nosocomial gram-negative infections Nephrotoxicity Ototoxicity Rare: Neuromuscular blockade with rapid high-dose use
18 Antibiotics (cont d) Tetracyclines Inhibit attachment of RNA to acceptor site Bacteriostatic Gram-positive and gram-negative microorganisms Rickettsiae Chlamydiae Mycoplasmas Spirochetes Protozoa Mycobacteria Gastrointestinal: Nausea, vomiting, diarrhea Inhibit bone growth and Ca, Mg, and Al, Fe absorption
19 Antibiotics (cont d) Tigecycline Inhibits protein synthesis (even against most tetracyclineresistant organisms) Complicated skin and intraabdominal infections Gastrointestinal: Nausea, vomiting, diarrhea, abdominal pain
20 Antibiotics (cont d) Macrolides Induce dissociation of transfer RNA from ribosome during elongation phase Bacteriostatic Atypical and community-acquired pneumonia Chlamydial infections in pregnant women Gastrointestinal complaints May increase concentration of other drugs Theophylline Warfarin Triazolam
21 Antibiotics (cont d) Telithromycin Inhibits bacterial protein synthesis Sinusitis and community-acquired pneumonia Gastrointestinal: Nausea and diarrhea Visual disturbances Prolonged Q-T interval
22 Antibiotics (cont d) Quinolones (Fluoroquinolones) Inhibit DNA synthesis Upper/lower respiratory infections Gastrointestinal infections Skin infections One of safest antimicrobial classes Gastrointestinal: Nausea, vomiting, diarrhea Prolonged Q-T interval
23 Other Antibiotics Chloramphenicol Inhibits protein synthesis Gastroenteritis/sepsis Salmonella Rickettsial diseases Bone marrow suppression Optic neuritis (blindness)
24 Other Antibiotics (cont d) Colistin (colistimethate) Surface active: Incorporates into cell membranes and causes disruption Systemic infections by gram-negative bacteria Nebulized against multidrug-resistant P. aeruginosa Reversible nephrotoxicity Dose-dependent neuromuscular blockade
25 Other Antibiotics (cont d) Daptomycin Possibly disrupts cytoplasmic membrane Complicated skin infections by gram-positive bacteria Staphylococcus aureus bacteremia Creatine phosphokinase (CPK) elevation Rhabdomyolysis
26 Other Antibiotics (cont d) Trimethoprim-sulfamethoxazole Blocks enzymes needed for bacteria to produce folic acid Bacteriostatic Pneumocystis carinii pneumonia (PCP) prophylaxis Acute bronchitis, otitis media, shigellosis Relatively well tolerated Nausea, vomiting, diarrhea, hypersensitivity Neutropenia, thrombocytopenia, hemolytic anemia, jaundice, hepatic necrosis, drug-induced lupus (all due to sulfamethoxazole)
27 Other Antibiotics (cont d) Clindamycin Inhibits protein synthesis Bacteriostatic Active against gram-positive and anaerobic bacteria Nausea, vomiting, diarrhea
28 Other Antibiotics (cont d) Metronidazole Unknown Anaerobic infections Trichomonas, Clostridium difficile Metallic taste, nausea, vomiting
29 Other Antibiotics (cont d) Nitrofurantoin Not certain Inhibits bacterial enzymes and protein synthesis? Damages bacterial DNA? Urinary tract infections (UTIs) Nausea, vomiting, hypersensitivity Pneumonitis
30 Other Antibiotics (cont d) Vancomycin Prevents formation of rigid cell wall Methicillin-resistant S. aureus (MRSA) Streptococcal endocarditis Red man syndrome Ototoxicity Nephrotoxicity
31 Other Antibiotics (cont d) Quinupristin and dalfopristin Inhibit protein synthesis MRSA Vancomycin-resistant Enterococcus faecium (VREF) Thrombophlebitis Arthralgia Myalgia
32 Other Antibiotics (cont d) Linezolid Prevents RNA translation VREF Diarrhea, nausea, headaches
33 Antimycobacterials Used against Mycobacterium tuberculosis Isoniazid Inhibits cell wall synthesis Hepatotoxicity Neurotoxicity
34 Antimycobacterials (cont d) Rifampin and rifabutin Inhibit RNA polymerase Hepatotoxicity
35 Antimycobacterials (cont d) Pyrazinamide Unknown Nausea and vomiting Hepatotoxicity
36 Antimycobacterials (cont d) Ethambutol Decreases synthesis of cell wall polysaccharides Bacteriostatic Optic neuropathy
37 Antimycobacterials (cont d) Streptomycin Similar to other aminoglycosides Nephrotoxicity Ototoxicity
38 Antifungals Polyenes (amphotericin B and nystatin) Increases permeability of cell membrane Aspergillosis, blastomycosis, histoplasmosis Flushing, fever, chills (infusion related) Renal impairment
39 Antifungals (cont d) Azoles Reduce ergosterol production Candidiasis (fluconazole) Anorexia Nausea Vomiting
40 Antifungals (cont d) Echinocandins Inhibit fungal cell wall synthesis Candida and Aspergillus Fever, rash, flushing, thrombophlebitis
41 Antifungals (cont d) Flucytosine Inhibits fungal RNA formation (fungistatic) Clinical use Candida, Cryptococcus, Aspergillus Bone marrow suppression
42 Antifungals (cont d) Griseofulvin and terbinafine Interferes with microtubule formation (griseofulvin) and reduces ergosterol production (terbinafine) Fungal infections of skin, hair, and nails Gastrointestinal: Heartburn, flatulence Headache
43 Antiviral Agents Acyclovir and valacyclovir Terminate viral replication Herpesvirus family Epstein-Barr virus (EBV) Cytomegalovirus (CMV) Varicella-zoster virus (VZV) Neuropathy Burning and irritation if used topically
44 Antiviral Agents (cont d) Penciclovir and famciclovir Interfere with viral DNA synthesis and replication Genital herpes simplex virus (HSV) and VZV Considered well tolerated Occasional nausea, vomiting, diarrhea, headache Rare neutropenia
45 Antiviral Agents (cont d) Ganciclovir and valganciclovir Terminates viral DNA synthesis and replication HSV, VZV, CMV Bone marrow suppression
46 Cidifovir Antiviral Agents (cont d) Inhibits viral replication Herpesvirus, EBV, CMV Dose-dependent nephrotoxicity Neutropenia, fever, headache, emesis, rash, diarrhea
47 Foscarnet Antiviral Agents (cont d) Blocks viral polymerase phosphorylation (inhibits viral replication) Herpesvirus, VZV, EBV, influenza A and B Nephrotoxicity (25%) Fever, nausea, vomiting, headache, diarrhea, electrolyte imbalance
48 Antiviral Agents (cont d) Fomivirsen Terminates viral transcription by binding to complementary sequences within viral nucleic acid CMV retinitis in patients with AIDS Transient increased intraocular pressures
49 Antiviral Agents (cont d) Amantadine and rimantadine Inhibit viral replication and assembly May inhibit uncoating of influenza virus Active against influenza A virus Adverse reactions Well tolerated CNS: Tremor, insomnia, lightheadedness, seizure, cardiac arrhythmias, agitation
50 Antiviral Agents (cont d) Oseltamivir Inhibits influenza A and B neuraminidase Prevents virus from leaving host cells Treatment of influenza A and B infection Nausea and vomiting in first 2 days of therapy
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