I. Microbial GrowthI. Sect. 4.1: Bacterial growtha. Lag phase  cells begin synthesizing enzymes required for growth1. There is no increase in cell #b. Log phase  “exponential phase,” cells divide at a constant ratec. Stationary phase  when nutrient levels are too low to sustain growthd. Death phase  a period when the total # of viable cells in pop decreases as cells die off at a constant ratee. Prolonged decline  the bacteria that survived the death phaseA. Sect. 20.1: Key players and terms1. Paul Erlich-a. Wanted to find a “magic bullet”b. Salvarsan-first antimicrobial agent2. Alexander Fleming-(Fig. 20.1)-discovered Penicillium (mold)3. Ernst Chain and Howard Florey*****- Were successful in mass producing penicillin and saved thousands of lives in WWII.4. Selman Waksman- found a soil bacterium which is source of streptomycin.B. Sect. 20.2: Characteristics of antimicrobial drugs1. Selective toxicity /Therapeutic index-2. Bacteriostatic vs bacteriocidal3. Broad spectrum vs narrow spectrum.4. Drug combinations can result in: only cidal when given in combination, but static individuallya. Antagonistic effectsb. Synergistic effectsc. Additive effects5. Tissue distribution/Metabolism/Excretiona. pH sensitive?b. Blood brain barrierc. Penicillin V versus Azithromycin6. Plasma half life7. Adverse effectsa. Toxicityb. Dysbiosis!!!!!  negative impact on your normal microbiota8. Innate/intrinsic resistance-organism cannot be acted upon because of inherent resistance.a. Intrinsic resistanceA. Minimum inhibitory concentration (MIC) is the lowest concentration of a specific antimicrobial drug needed to prevent visible growth of a given organism in vitro, without killing (Fig. 20.9).1. The MIC is determined using serial dilutions of one antimicrobial drug.2. In vivo, differences in absorption and distribution of the antibiotic will influence the dose, route, and frequency of administration of the antibiotic in order to achieve the MIC at the site of infection.B. Minimum bactericidal concentration (MBC)  what [] kills1. Lowest [] that kills 99.9% of the original inoculum2. Other aspects to consider for dosing:a. Concentration dependent killing is a short course, high concentration. You must get to a specific serum level to achieve antimicrobial effect.b. Time-dependent killing- the MIC must be achieved for a specified duration in order to achieve antimicrobial effect.3. Ways to test the MIC, as well as if an organism is: Antibiotic Resistance/Sensitive/Intermediatea. Antibiotic Resistanceb. Kirby-Bauer Method (Fig. 20.10)-tests bacterial susceptibility against an array of antibiotics.1) Test can be used to test on gram-positive organism  can test against all gram-positive antibiotics to see if it is resistant or sensitivea. Resistant = the zone is not big enoughb. Sensitive = if zone is correctc.d. Can test 12 different antibiotics  bc of zonesc. E-test (Fig. 20.12)- can tell MIC to an array of antibioticsc.B. Mechanisms of acquired antimicrobial resistance (Fig. 20.14)1. Drug-inactivating enzymes2. Alteration in target molecule3. Decreased uptake of drug4. Increased elimination of drug5. R plasmids6. Innate resistance  due to basic metabolism or structure that enables resistanceC. Emerging Resistance (Table 20.2)1. Problematic organisms  are now affecting the world = super bugsa. C. diffb. CRE (Enterobacteriaceae)c. Drug resistant Neisseria gonorrhoeaed. Mycobacterium tuberculosise. MRSA, VISA2. How can we combat?a. Combination therapyb. Generate new antibiotics?a. Penicillins and members of penicillin family- all have same beta-lactam ring, semi-synthetic types of these drugs simply modify the side-chain to change spectrum of action.1) Natural penicillins: penicillin V (oral) vs penicillin G (injected)2) Broad spectrum semi-synthetic: ampicillin, amoxicillin3) Penicillinase resistant semi-synthetic: Methicillinb. Cephalosporins- Five generations*: all start with the prefix: Cef ___. First generation worked best against Gram-positives, later generations were designed to work best against Gram-negatives (and lost the ability to target Gram-positives effectively. Later generations are more resistant to beta-lactamases, and the fifth generation is used to treat MRSA.c. Carbapenems : imipenem*, Broad spectrum, not inactivated by extended spectrum beta-lactamases (ESBLs), but sensitive to carbapenemases (which can act on all beta-lactamases).d. Monobactams: aztreonam*, can target Gram-negatives, especially members of the Enterobacteriaceae family. Can be inactivated by ESBLs.3. Bacitracin-active only against Gram-positive bacteria, targets bactoprenol**. Toxicity (low therapeutic index) limits it to topical treatments.1. Fluoroquinolones (Cidal): Ciprofloxacin-DNA replication2. Metronidazole (Cidal): DNA replication, Only works against anaerobic organisms3. Rifamycins (Cidal): Rifampin, overuse creates resistant organisms (RNA polymerase)1. Sulfonamidesa. Referred to as sulfa drugs, inhibit the growth of many Gram-positive and negative bacteriab. The enzyme that binds para-aminobenzoic acid (PABA) binds sulfa drugs insteadc. Resistance is due to the acquisition of a plasmid that encodes an enzyme the medication does not bind to as well2. TrimethoprimC. Cell membrane Integrity  also low therapeutic membrane  cause cells to leak, leading to cell death1. Daptomycin (Cidal): Gram-positive2. Polymyxin B (Cidal): Gram-negativeD. Ethambutol, Isoniazid and Pyrazinamide-act specifically on the synthesis of the cell wall of Mycobacterium tuberculosis.V. Antiviral drugs (Fig. 20.15)1. Viral entry: HIV only2. Viral uncoating: Amantadine Rimantadine- only used against Influenza, most strains now resistant.3. Nucleic acid synthesis (Only DNA herpesvirus family members, HIV, Hepatitis C)a. RNA dependent RNA polymerases- Hep. C: only anti-viral that can CURE the infection.b. Nucleoside analogs: terminates DNA synthesis during replication of genome.c. Non-nucleoside polymerase inhibitors: inhibits viral polymerase.d. Non-nucleoside reverse transcriptase inhibitors: inhibits Reverse transcriptase.4. Integrase Inhibitors-HIV only5. Assembly and release of viral particles:a. Protease inhibitors (only HIV),b. Neuraminidase inhibitors (only influenza: Tamiflu, Renlenza).VI. Antifungal drugs: (Table 20.4) You will not need to know any names of fungal drugs.D. Risk for infection-critical vs non-critical instrumentsE. Composition of items to be disinfected3. Sect. 5.3 and