Test 4 Flashcards
1
Q
Selective Toxicity
A
***the ability of a drug to inquire a target cell or organism without injuring other cells or organisms that are non-targeted.
2
Q
Disruption of the bacterial cell wall:
A
bacteria are encased in a rigid cell wall that encases a very hypertonic solute. If not for the rigid cell wall, water would follow the osmotic gradient, causing bacterial swelling and ultimate bursting. Several antibiotics work to weaken the cell wall.
3
Q
Inhibition of enzymes unique to the bacteria:
A
inhibiting specific enzymes that are critical to bacterial survival.
4
Q
Disruption of protein synthesis:
A
we can impair protein synthesis in bacterial cells. Selective because bacterial ribosomes are different than mammalian ribosomes.
5
Q
Narrow spectrum Antibiotics:
A
active against only a few bacteria
6
Q
Broad Spectrum Antibiotics:
A
active against a wide variety of bacteria
7
Q
Bactericidal:
A
Bacterial Killers
8
Q
Bacteriostatic:
A
Suppress Growth, but do not kill
9
Q
Normal Flora:
A
Body’s normal bacterial and fungal community
10
Q
Pathogen:
A
overgrowth or introduction of new bacteria that causes an infectious response to the host
11
Q
Aerobes vs Anaerobes:
A
Aerobes require oxygen to survive and Anaerobes do not.
12
Q
Superinfection:
A
Secondary infection with resistant bacteria
13
Q
Nosocomial Infections:
A
Infections acquired in hospitals and nursing homes. Typically very drug resistant.
14
Q
MIC
A
.
15
Q
MBC
A
.
16
Q
Resistance:
A
organisms that were highly responsive to an antibiotic that becomes less susceptible over time (ex staph, strep, Pneumo, Klebsiella, Enterococcus)
17
Q
Mechanisms of Bacterial Resistance-
A
- Production of drug-metabolizing enzymes (ex Penicillinase)
- Cease active uptake of the drug
- Altered receptor sites- example penicillin binding proteins.
- Synthesis of compounds that antagonize actions of the antibiotic (ex bacteria develop ability to synthesize PABA, which leads to Sulfonamide resistance)
18
Q
Acquiring resistance-
A
- Spontaneous Mutation- Random changes in a bacterial DNA. Leads to very Low level resistance. Additional mutations leads to greater resistance.
- Conjunction- where bacteria “Communicate” to one another and share/transfer DNA that leads to resistance (sometimes multi-drug resistance.
19
Q
Antibiotics and the Emergence of Resistance
A
** ABX can promote overgrowth of bacteria that have acquired mechanisms of resistance***
20
Q
NORMAL BACTERIAL FLORA
A
Under drug free cond., bacteria keep eachother under check. They secrete toxic compounds that are toxic to other bacterias well as compete for nutrients.
21
Q
SUPERINFECTIONS-
A
new infection that develops during the course of treatment of a primary infection. Normal Flora is altered allowing for resistant organism to flourish.
22
Q
NARROW SPECTRUM VS. BROAD SPECTRUM-
A
Broad spectrum kill off more of the normal flora, thus the more broad spectrum, it can more than likely facilitate the emergence of superinfections.
23
Q
INDISCRIMINATE USE OF ABX-
A
he more bacteria SEE an antibiotic, the more opportunity to delelop resistance. Much of our resistance issues today are secondary to improper abx use.
24
Q
CDC CAMPAIN TO PREVENT ANTIMICROBIAL RESISTANCE.
A
- VACCINATE- especially flu and Pna
- GET THE CATHETERS OUT- IV,ART,URINARY,ET, ETC…
- TARGET THE PATHOGEN** CULTURES AND SENSITIVITY** Always obtain prior to initial ABX use.
- ACCESS THE EXPERTS- input from infectious disease experts.
- PRACTICE ANTIMICROBIAL CONTROL- ABX SURVILLANCE PROGRAMS, order sets, education, feedback.
- USE LOCAL DATA.- ANTIBIOGRAM-assista in guiding initial drug selection
- TREAT INFECTION- NOT CONTAMINATION ** obtain samples correctly, decontaminate skin, etc,,,**
- TREAT INFECTION, NOT COLONIZATION- ex Sputum samples, skin swabs
- JUDICIOUS USE OF VANC.- Drug of last resort for MRSA and multi-drug resistant strep pneumo
- STOP ABX AT THE PROPER TIME
- ISOLATE THE PATHOGEN- proper isolation of PTs, disposal of body fluids, proper cleaning of hospital rooms
- WASH YOUR HANDS! AT LEAST 50%FAILURE
RATE
25
ANTIBIOTIC SELECTION: EMPERIC THERAPY:
***in severe infections, you may have to initiate ABX therapy before test results are available***
1. BROAD SPECTRUM- INITIAL
2. NARROW THE SPECTRUM: AFTER THE BACTERIA IS ISOLATED AND CULTURE ANS SENSITIVITY RESULTS RETURN
26
ANTIBIOTIC SELECTION: IDENTIFYING THE ORGANISM
1. GRAM STAIN- Quick analysis through gram staining – tells if gram+ cocci, gram- cocci, gram neg rod, or gram + rods. This can narrow the choices of empiric treatment.
2. culture-place sample on medium conducive to bacterial growth.
27
ANTIBIOTIC SELECTION: DRUG SUSCEPTIBILITY-
mainly used for organisms that have high incidence of resistance. To guide appropriate ABX useage.
DISK DIFFUSION-
Broth Dilution Test-
28
DISK DIFFUSION-
inoculating an agar plate, then place discs that contain different ABX on the agar plate. The degree of sensitivity is proportional to the size of the bacteria free zone around the disk.
29
Broth Dilution Test-
Bacteria are grown in a series of tubes containing different concentrations of different antibiotics. We can establish:
1. Minimum Inhibitory Concentration (MIC)- Lowest concentration of an antibiotic that produces complete inhibition of bacterial growth.
2. Minimum Bactericidal Concentration (MCB)- lowest concentration of drug that produces a 99.9% decline in the number of bacterial colonies.
30
Host Defenses-
Immune system. Without an intact immune system, antibiotics are rarely successful. (Ex AIDS). Goal typically is to suppress bacteria enough to tip the scale back in the direction of the host immune defenses. If poor immune function, need to be VERY aggressive with CIDAL antibiotics. Cannot afford to miss.
31
Site of Infection-
Antibiotics must be able to get to the site of infection in sufficient concentrations (typically 4-8 times the MIC)
1. CNS Infections - BBB
2 . Pneumonia
3. Abscesses
32
Doses and Duration:
1. Dosage:
```
Success resides in obtaining adequate concentrations of
effective antibiotics (typically 4-8 times the MIC) for sufficient periods of time. Must keep in mind pharmacokinetic variables such as ADME- Absorption, Elimination, Metabolism, and Distribution. Things important such as kidney functions, body weight, volume of distribution, site of infection, MIC ect..
```
33
Doses and Duration:
2. Duration:
Differ depending on variables such as:
A. Site of infection - (ex. Simple UTI, vs. Endocarditis vs Prostatitis)
B. Host Defenses
C. Bug Being Treated
34
***** IMPORTANT TO TREAT LONG ENOUGH.
Important to tell patients to continue their medication for the full length of time, even though they may feel better (Even Normal). Early Antibiotics withdrawal is a big cause of recurrent infection and drug resistance. ********
35
Combination Therapy:
1. Effects:
a. Additive - 1 + 1 = 2 (Clarithromycin Plus Amoxicillin For H.Pylori)
b. Synergistic - 1 + 1 = 5 (Trimethoprim + Sulfamethoxazole / Piperacillin + Gentamycin. )
c. Antagonistic- 1 + 1 = 0 (Tetracycline plus Penicillin)
36
Combination Therapy:
2. Indicated:
a. Severe infection- Until the pathogen has been identified. Broad Empiric coverage
b. Mixed Infections- perforated bowel, diabetic foot, dog bite
c. Prevention of resistance- TB
d. Enhanced Antibiotic Activity.- Penicillin plus Aminoglycoside
(PCN weakens the cell wall and allows for great penetration of the AMG)
37
Prophylactic Antibiotic Use- ALMOST NEVER INDICATED EXCEPT
1. Surgery- ex Cefazolin pre surgery
2. Bacterial Endocarditis- individuals with congenital, valvular heart disease, or prothetic valves take antibiotics before dental procedures and surgery
3. Neutropenia- ex Bactrim DS in AIDS Patients to prevent Pneumonia
4. Influenza Outbreaks- Amantadine/ Ramantadine
38
Monitoring Clinical Response
1. Fever Curves
2. WBC: Bands
3. Regression of Erythema (For Tissue Infections)
4. Improvement in Chest Xray for Pneumona
5. General Improvement in health Status
39
GRAM POSITIVE COCCI- Stain little, round, and blue
1. STAPH AUREUS- skin bug Can be very aggressive. Micro-abcesses.
2. STAPH-EPI- skin bug Normally do not cause infection unless immunocompromised. Often a contaminant. Sometimes associated with line infections.
3. STREP A- Strep throat
4. STREP B- post partum infections
5. STREP PNEUMO- aggressive. Upper resp. #1 pathogen for pneumonia, sinusitis, ear infections.
6. ENTEROCOCCUS- from mouth to gut. Used to be called group D strep. Becoming extremely resistant (VRE)
Pepto and peptostrepto-
7. ANAEROBES. Grow in mouth, Typically not a problem unless very poor hygiene.
40
GRAM POSITIVE COCCI- Stain little, round, and blue
STAPH AUREUS
skin bug Can be very aggressive. Micro-abcesses.
41
GRAM POSITIVE COCCI- Stain little, round, and blue
STAPH-EPI-
skin bug Normally do not cause infection unless immunocompromised. Often a contaminant. Sometimes associated with line infections.
42
GRAM POSITIVE COCCI- Stain little, round, and blue
STREP A-
Strep throat
43
GRAM POSITIVE COCCI- Stain little, round, and blue
STREP B
post-pardom infections
44
GRAM POSITIVE COCCI- Stain little, round, and blue
STREP PNEUMO
aggressive. Upper resp. #1 pathogen for pneumonia, sinusitis, ear infections.
45
GRAM POSITIVE COCCI- Stain little, round, and blue
ENTEROCOCCUS-
from mouth to gut. Used to be called group D strep. Becoming extremely resistant (VRE)
46
GRAM POSITIVE COCCI- Stain little, round, and blue
Pepto and peptostrepto- ANAEROBES.
Grow in mouth, Typically not a problem unless very poor hygiene.
47
GRAM POSITIVE RODS: STAIN BIG, BLUE, RODS
1. LISTERIA- May be in the very old, or very young. Can cause meningitis or pulmonary infection
2. C.DIFF- GI bug. Very resistant to bacteria Can be a superinfection that causes PSEUDOMEMBRANOUS COLITIS.
48
GRAM POSITIVE RODS: STAIN BIG, BLUE, RODS
1. LISTERIA-
May be in the very old, or very young. Can cause meningitis or pulmonary infection
49
GRAM POSITIVE RODS: STAIN BIG, BLUE, RODS
2. C.DIFF-
GI bug. Very resistant to bacteria Can be a superinfection that causes PSEUDOMEMBRANOUS COLITIS.
50
GRAM NEGATIVE COCCI: STAIN LITTLE ROUND AND RED.
1. Neisseria meningococcus- Can cause drastic infection. Very quick and aggressive. Eppidemics.
2. NEISSERIA GONOCOCCUS- Gonorrhea
3. MORAXELLA- upper respiratory (sinusitis, ear, Pneumonia).
51
GRAM NEGATIVE COCCI: STAIN LITTLE ROUND AND RED.
1. Neisseria meningococcus-
Can cause drastic infection. Very quick and aggressive. Eppidemics.
52
GRAM NEGATIVE COCCI: STAIN LITTLE ROUND AND RED.
2. NEISSERIA GONOCOCCUS-
GONOCOCCUS- Gonorrhea
53
GRAM NEGATIVE COCCI: STAIN LITTLE ROUND AND RED.
3. MORAXELLA-
upper respiratory (sinusitis, ear, Pneumonia).
54
GRAM NEGATIVE RODS: STANI BIG, ROD SHAPED, AND RED
1. PSEUDOMONAS- usually nonpathogenic. Very resistant. TWO BUG DRUG.
2. B. FRAG- ANAEROBIC Resistant to beta lactams AND cephalosporins due to beta lactamase prodx. (WONT WORK).
3. SALMONELLA/ SHIGELLA- GI BUGS (DIARRHEA). Travellers diarrhea. (esp salmonella)
4. E. COLI- # 1 PATHOGEN IN UTIs (esp in women)
5. H. FLU - UPPER RESP TRACT INFECTIONS
6. ACINETOBACTER- major resistance problems in hospitals/ nursing homes
55
GRAM NEGATIVE RODS: STANI BIG, ROD SHAPED, AND RED
PSEUDOMONAS-
usually nonpathogenic. Very resistant. TWO BUG DRUG.
56
GRAM NEGATIVE RODS: STANI BIG, ROD SHAPED, AND RED
B. FRAG-
ANAEROBIC Resistant to beta lactams AND cephalosporins due to beta lactamase prodx. (WONT WORK).
57
GRAM NEGATIVE RODS: STANI BIG, ROD SHAPED, AND RED
SALMONELLA/ SHIGELLA- GI BUGS (DIARRHEA).
Travellers diarrhea. (esp salmonella)
58
GRAM NEGATIVE RODS: STANI BIG, ROD SHAPED, AND RED
E. COLI-
1 PATHOGEN IN UTIs (esp in women)
59
GRAM NEGATIVE RODS: STANI BIG, ROD SHAPED, AND RED
. H. FLU
UPPER RESP TRACT INFECTIONS
60
GRAM NEGATIVE RODS: STANI BIG, ROD SHAPED, AND RED
ACINETOBACTER-
major resistance problems in hospitals/ nursing homes
61
ATYPICALS-
Cause infections that look like other infections. Don’t gram stain! Hard to ID!
1. mycoplasma- not typically that severe. Walking man’s PNA
2. LEGIONELLA- Can be severe
3. CHLAMYDIA- upper resp and GYN
62
PENICILLIN MOA-
Weakens cell wall causing lysis and death (bactericidal). Rigid cell wall with high osmotic pressure.
63
PENICILLIN RESISTANCE-
GRAM POSITIVE have 2 layer cell membranes that PCN can easily penetrate, however, GRAM NEGATIVE have 3 layer cell membranes. Difficult for PCN to penetrate and bind to PBP’s. (Penicillin binding proteins).
1. PBP’s- PENICILLIN BINDING PROTEINS ** TARGET FOR PCN ON THE CELL WALL.*** Expressed only when actively growing. Bacteria are altering the PBPs making it harder for PCN to bind.
2. BETA LACTAMASES- enzymes which cleave beta lactam rings EX- STAPH in the 1940’s 100% sensitive, in 1960’s 80% resistance. Many G+ and G- produce.
64
CLASSIFICATION-
NARROW SPECTRUM-
(Penicillinase sensitive) (ex PENICILLIN G)
1. SPECTRUM: GRAM POSITIVE COCCI, (non penicillinase producing), GRAM NEGATIVE COCCI, GRAM POSITIVE ANAEROBES, SPIROCHETES
2. MAIN USE STREP THROAT AND SYPHILIS***MULTIPLE FORMS Pen-G PO, depot forms for IM injection, IV.
3. DISTRIBUTION- In the abcense of inflammation, poor CNS penetration
4. PK- RENALLY ELIMINATED
5. ALLERGIES: MOST COMMON DRUG ALLERGY!!! From rash to anaphylaxis. Allergic to one, allergic to all. 1st dose, stay in office for 30 min. Epi on hand. Alternatives: ERY, VANC, POSSIBLY CEPHALOSPORINS
65
What is the most common drug allergy?
Pennicillin
ALLERGIES: MOST COMMON DRUG ALLERGY!!! From rash to anaphylaxis. Allergic to one, allergic to all. 1st dose, stay in office for 30 min. Epi on hand. Alternatives: ERY, VANC, POSSIBLY CEPHALOSPORINS
66
NARROW SPECTRUM (Penicillinase resistant antistaphlococcal penicillin) (ex. Methicillin)
DRUGS- METHICILLIN (obsolete), NAFCILLIN (IV), OXACILLIN, DICLOXACILLIN
SPECTRUM: INDICATED for PCNase producing staph (staph aureus and staph epi)
2, MRSA- altered PBPs. VANCOMYCIN IS DOC
67
BROAD SPECTRUM:
AMOXICILLIN AND AMPICILLIN
SPECTRUM: PCN( gram + cocci (non pcnase producing), gram – cocci, gram + anaerobes, spirochetes, plus some G- rods (H flu, E COLI, Salmonella, Shigella) PLUS strep throat and syphilis.
PCNase- still inactivated by PCNase, so poor for staph and other PCNase producing G-
68
EXTENDED SPECTRUM PENICILLINS
DRUGS: PIPERACILLIN, TICARCILLIN
SPECTRUM: AMOXICILLIN (gram + cocci (non pcnase producing), gram – cocci, gram + anaerobes, spirochetes, plus some G- rods (H flu, E COLI, Salmonella, Shigella) PLUS strep throat and syphilis.) ( PLUS PSEUDO, PROTEUS, SOME KLEBSIELLA
USES: MOSTLY FOR PSEUD (IN COMBO WITH AMG)
TICARCILLIN- VERY LARGE Na+ loads. Caution with CHF and Renal failure pts.
69
E.BETA LACTAMASE INHIBITORS (not ABX)
1. CLAVULANIC ACID, TAZOBACTAM, AND SULBACTAM
2. MOA: Inhibits beta lactamase. Combined with PCNs to extend their spectrum to some beta lactamase bacteria (staph aureas, Staph Epi, B. Frag, Proteus, H.Flu).
70
What is the MOA of CEPHALOSPORINS
MOA: BETA lactams (bacterialcidal) ***similar to PCN but more stable against beta lactamase producing bacteria *** Bind to PBPs and disrupt cell wall synthesis.
71
What is the Spectrum of activity of CEPHALOSPORINS
SPECTRUM OF ACTIVITY: AS one progresses from 1st generation to 4th generation
1. Increased activity against G- rods
2. Increased resistance to beta lactamase
3. Increased ability to penetrate the CNS (Meningitis).
72
1ST GENERATION CEPHALOSPORINS
(cefazolin/cephalexin)
gram postitve (staph,strep). If MRSA, resistant however. Essentially no G- coverage
73
2nd GENERATION CEPHALOSPORINS
( cefuroxime and cefotetan)
GRAM +( STAPH,STREP,ENTEROCOCCUS,PEPTOCOCCUS, PEPTOSTREPTOCOCCUS,C DIFF, TETANI,PERF, LISTERIA PLUS SOME GRAM –(E.COLI,H.FLU,PROTEUS, MORAXELLA)
74
3RD GENERATION CEPHALOSPORINS
(Cephtazidime and Ceftriaxone) KEEPS BUGS-
CEFTAZIDIME IS THE ONLY ONE THAT HAS EXCELLENT PSEUD COVERAGE, AND EXCELLENT CNS PENETRATION.
75
4TH generation CEPHALOSPORINS
(CEFIPINE) Resistant to Beta Lactamases and Pseudomonas. VERY BROAD
76
CEPHALOSPORINS P’KINETICS
1. CSF PENETRATION. Best with 3rd and 4th generation Cephs.
| 2. Renal adjustment not necessary for cefoperazone and ceftriaxone
77
CEPHALOSPORINS ADVERSE DRUG REACTIONS
1. HYPERSENSITIVITY- 5-10% CROSS REACTIVITY TO pcn ALLERGIES
2. BLEEDING- cefmetazole, cefoperazone, cefotetan ****interferes with vit k metabolism. Prolongs PT (LIKE COUMADIN). Monitor INR and can treat with Vit K!*****
3. DISULFIRAM- CEFMETAZOLE, CEFOPERAZONE, CEFOTETAN
78
CARBAPENEMS- used with CILASTATIN, AN enzyme inhibitor.
DRUGS—IMIPENEM, MEROPENEM, ERTAPENEM
79
What is the spectrum of activity for IMIPENEM, MEROPENEM, ERTAPENEM?
SPECTRUM GRAM + AND GRAM –( esp. pseudomonas) and Anaerobes (Extremely broad spectrum). Broadcast single ABX we have. ***resistant to PCNases and great penetration into the G- cell walls.
80
What is the Pharmacokinetics of IMIPENEM, MEROPENEM, ERTAPENEM?
P’kinetics- Combined with CILASTATIN to improve urine concentrations. IMIPENEM is metabolized by dipeptidase at the renal brush border. CILASTATIN Inhibits dipeptidase.
81
What are the ADEs of IMIPENEM, MEROPENEM, ERTAPENEM?
ADEs hypersensitivity, superinfections, seizures, allergic cross reactivity with PCN
82
What are the uses of IMIPENEM, MEROPENEM, ERTAPENEM?
USES- SERIOUS INFECTIONS, PSEUDOMONAS, MIXED INFECTIONS
83
MONOBACTAMS: AZTREONAM
MOA:
Binds to PBPs, but only Gram – cocci and rods (NEISSERIA GONOCOCCUS, NEISSERIA MENINGOCOCCUS, MORAXELLA CATHARRALIS, KLEBSIELLA,E.COLI, ENTEROBACTER, PROTEUS, PROVIDENTIA, SERRATIA, SALMONELLA, SHIGELLA, H. FLU, ACINETOBACTER, PSEUDOMONAS, B.FRAGELLA, CITROBACTER).
84
MONOBACTAMS: AZTREONAM SPECTRUM-
SPECTRUM- GRAM – AEROBES, NEISSERIA, H.FLU, PSEUDOMONAS, ENTEROBACTERIACIAE (E.COLI, KLEBSIELLA, PROTEUS,SERRATIA, SALMONELLA, SHIGELLA)
Parenteral only
Appears safe in pts with PCN allergies
Expensive
85
VANCOMYCIN
| MOA:
DISRUTS CELL WALL SYNTHESIS BUT DOES NOT DO SO VIA PBPS. Binds to precursor molecules for cell wall synthesis.
86
VANCOMYCIN SPECTRUM-
GRAM +COCCI AND GRAM +RODS DOC FOR MRSA (AND USED TO BE FOR C.DIFF) Also used for gram + infections when PCN allergic.
87
VANCOMYCIN P’KINETICS-
NOT ABSORBED WELL ORALLY (THIS IS A GOOD THING FOR TREATING c-Diff because it sits in the gut and does its job.
Used IV for systemic infections
88
VANCOMYCIN ADE:
RED MAN SYNDROME- Give over 60 min or more. Massive release of histamine
NEPHROTOXICITY- not as much as once thought. Must check trough levels to ensure adequate clearance (typically <15-20 mcg/ml)
89
What are the BACTERIOSTATIC INHIBITORS OF PROTEIN SYNTHESIS
TETRACYCLINES, MACROLIDES, AND OTHERS
90
TETRACYCLINEs: Extensive use has resulted in resistance. Use hs declined
Drugs- TETRACYCLINE, MINOCYCLINE, DOXYCYCLINE
MOA:
Inhibits protein synthesis in the cell, preventing reproduction. Binds to the 30s subunit of the ribosome
91
TETRACYCLINE, MINOCYCLINE, DOXYCYCLINE SPECTRUM:
SPECTRUM: ATYPICALS (LEGIONELLA, MYCOPLASMA, CHLAMYDIA), AND H.PYLORI MOSTLY
92
TETRACYCLINE, MINOCYCLINE, DOXYCYCLINE THERAPEUTIC USES:
ROCKY MOUNTAIN SPOTTED FEVER, CHLAMYDIA, BRUCELLOSIS, CHOLERA, MYCOPLASMA, LYME DISEASE, H.PYLORI, ACNE, UNCOMPLICATED UPPER RESP TRACT INFECTIONS.
93
TETRACYCLINE, MINOCYCLINE, DOXYCYCLINE P’KINETICS:
DO NOT administer with milk or other high calcium products, iron, magnesium antacids (interferes with absorbtions) Administer 2 hr. before or 2 hrs. after.
94
TETRACYCLINE, MINOCYCLINE, DOXYCYCLINE ADEs
GI: Irritant-can cause esophageal ulceration. Avoid HS dosing. Take with full glass of water.
BONES AND TEETH- binds to calcium, causing a yellow/brown discoloration to teeth
Photosensitivity- use sunscreen
95
Macrolides- Erythromycin, Azythromysin, Clarithromycin
| MOA:
inhibition of protein synthesis. Binds to the 50S subunit of the ribosome.
96
Macrolides- Erythromycin, Azythromysin, Clarithromycin Spectrum/ Therapeutic uses-
Gram-positive cocci, Atypicals. Alternative in PCN allergic patients. Azithromycin, Clarithromycin have reasonable H. Flu and Moraxella coverage.
97
Macrolides- Erythromycin, Azythromysin, Clarithromycin Pharmacokinetics:
central nervous system penetration is poor.
Enzyme inhibitor- caution with the open Theophylline, carbamazepine, and Warfarin. ( Erythromycin primary, but watch for all. )
98
Macrolides- Erythromycin, Azythromysin, Clarithromycin Adverse drug reactions.
Adverse drug reactions.
Gastrointestinal upset pain with nausea and vomiting.
QT prolongation and torsades avoid with other CYP three A4 inhibitors.
Phlebitis- IV. Must dilute Heavily.
99
Clindamycin-
MOA-
Inhibition of protein synthesis by binding to 50S subunit of the ribosome.
100
Clindamycin-
Spectrum:
Spectrum: Gram + aerobes and anaerobes. Utilization mainly for anaerobic coverage.
101
Clindamycin- ADE-
ADE- Pseudomembraneous Colitis -> superinfection of the bowel with C- Diff (Anaerobic G+ rod). Treatment is PO Vancamycin or PO Metronidazole.
102
Linezolid (Zyvox)
MOA-
MOA- Bind to the 23S portion of the 50S ribosomal subunit. Very Unique, thus cross resistance is rare.
103
Linezolid (Zyvox) Spectrum:
Spectrum: MRSA, VRE, Should only be used for these infections. No activity for Gram Negative.
104
Linezolid (Zyvox) ADR:
Myelosuppression ( Check CBC every week )
Drug Interactions- Weak inhibitor of MAO, do not use with sympathomimetics or foods containing tyramine.
105
Quinupristin / Dalflopristin (Synercid)
MOA-
2 drugs which inhibit protein synthesis ****(synergy).
106
Quinupristin / Dalflopristin (Synercid)
| Use:
Vancomyocin resistant E. Faecium, MRSA, Multi-Drug resistant strep pneumo.
107
Quinupristin / Dalflopristin (Synercid)
| Drug Interactions-
CYP450 Inhibitor
ADE-
1. Hepatoxicity- check LFT’s twice during 1st week then weekly thereafter,
Thrombophlebitis- 50% incidence. Often needs central line administration.
Safe in PCN allergic patients.
108
name the Aminoglycosides:
Gentamicin, Tobramycin, Amikacin
Narrow spectrum, bactericidal, given parenterally.
109
Gentamicin, Tobramycin, Amikacin
MOA-
Binds to 30S Ribosomal subunit and inhibits protein synthesis. Drugs that work through this mechanism are generally static. However, the AMG cidal activity occurs from the production of abnormal proteins that insert themselves into the cell membrane, causing weakness and leaking to occur.
110
Gentamicin, Tobramycin, Amikacin
Resistance-
via bacterial production of enzymes capable of inactivating the AMG.
Amikacin is resistant to these enzymes.
111
Gentamicin, Tobramycin, Amikacin Spectrum:
Spectrum: Especially Gram Negative rods and some G+ cocci (Staph and Enterococcus). No Anaerobic Activity.
112
Gentamicin, Tobramycin, Amikacin
Use:
Treatment of severe nosocomial infections, esp. Psudomonas and KEEPS bacteria.
113
Gentamicin, Tobramycin, Amikacin
Pharmacokinetics:
Postantibiotic Effect= bactericidal activity persists several hours after serum levels have dropped below MBC.
Interpatient Variability- Must individualize the dosing and sometimes levels are unpredictable. Must take into account wt, RFx, site of infection, peak goal. ect.
Concentration dependent killers.
Pharmacokinetics: Highly polar compounds. Thus IV only and very poor CNS penetration. Highly concentrated in the inner ear and kidneys ->
Toxicity. Drugs are eliminated in the kidneys.
Peaks must be high enough for efficacy, but with troughs low enough to limit toxicity.
Conventional dosing of
Gentamicin and Tobramycin:
Peaks: 0.5 - 1 hour after end of infusion (Range 4-10 ug/ml)
Trough: Just before the next dose (Range 0.5 - 2 ug/ml)
Recording timing of doses and timing of blood sample (Levels) VERY IMPORTANT!
114
Gentamicin, Tobramycin, Amikacin ADE:
Ototoxicity- via accumulation, can cause cochlear damage (hearing) and vestibular damage (balance). Early cochlear damage is initiated by tinnitus (ringing). Early vestibular damage is manifested by HA/ Nausea/ Dizziness. Damage is dependent on elevated trough levels. Need time to wash out. Prolonged exposure equals toxicity. Largely irreversible.
Nephrotoxicity- related to accumulative doses as well as elevated trough levels. Can manifest early on as proteinuria, elevated BUN, and elevated serum creatinine.
Neuromuscular blockade- can inhibit neuromuscular transmission. Patient is at highest risk are those with myasthenia gravis.
115
Gentamicin, Tobramycin, Amikacin Dosing schedule-
QDAY vs. Q8. Since concentration deptendent killer and post antibiotic effect, potentially greater kill and less toxicity with QDAY vs Q8. Less laborious (peaks, troughs, pharmacokinetic specialists ect) Much higher peaks with QDAY and greater wash out period.
116
Drug differences:
| Gentamicin-
Cost: Cheapest
Combo Therapy: Typically combined with another antibiotic. (PCN / CEPH / or VANC)
Administration: IV, IM, Intrathecal
117
Drug differences:
Tobramycin:
Psudomonas: Slightly better for Pseudomonas as compared to Gentamycin, but slightly less activity for G+ cocci.
Cost: significantly more expensive than Gentamycin.
Resistance: Generally if resistant to Gentamycin, probably resistant to Tobramycin
Administration: IV / IM / Nebulized (CF)
118
Drug differences:
Amikacin:
```
Spectrum: Broad Spectrum for Gram Negative Rods. Klebsiella,
E-coli,
Enterobacter,
Proteus,
Providentia,
Serratia,
Salmonella,
Shigella.
H.Flu ,
Acinetobacter,
Psudomonas,
B.Fragilis,
Citrobacter
```
Resistance: Least vulnerable to inactivation by bacterial enzymes.
Cost: Very Expensive
Use: Typically reserved for infections that are resistant to Gentamicin and Tobramycin.
119
Sulfonamides :
** Sulfonamides were the 1st drugs available for systemic bacterial infections. They preceded PCN.
Overview Sulfonamides: structural analogs of PABA (Para-aminobenzotic acid) **--Vit B Family and is part of the folic acid structure.
120
Sulfonamides : MOA-
MOA- Folic acid is a compound required for the synthesis of DNA, RNA, proteins (All Cells). However, bacteria are unable to take up folate from their surroundings. Must synthesize their own. Sulfonamides inhibit the synthesis of folic acid in bacteria. They will utilize the sulfonamide instead of PABA ant try to synthesize the folic acid.
121
Sulfonamides:
Spectrum:
```
Spectrum: Gram Positive Cocci
Staph
Strep
Enterococcus
Peptococcus
Peptostreptococus
(sometimes even MRSA),
Clamydia,
P.Carinii,
G.Bactilli (Esp H.Flu/E.Coli)
```
122
Sulfonamides :
| Therapeutic Uses:
3. Therapeutic Uses: UTI, URTI, Sometimes PO therapy for Resolving MRSA if sensitivity data supports.
123
Sulfonamides : Side Effects:
Side Effects:
Hematologic:
Hemolytic Anemia: G6PD Deficiency Anemia. (AA, Mediterranean Decent , Greek, Italian, Spanish, Portugese) ** Interesting that malaria does not survive as well in G6PD deficient patients. Thus it is believed that this was an acquired protective mechanism against malaria.
Agranulocytosis
Thrombocytopenia
Aplastic Anemia
Skin Reactions:
Photosensitivity
Mild Rashes
Stevens Johnsons. Mortality approx 25% ** Watch for cross sensitivity with loops, thiazides, sulfonylureas, celecoxib**
Kernicterus: In Newborns. Displaces billirubin from Albumin. Can Deposit into the brain and cause neurologic side effects. Don’t give to less than 2 months old, pregnancy, or breastfeeding.
Crystalluria- crystalizes out in the urine. Can cause renal toxicity. Uncommon in today’s generation of sulfonimides as the have enhanced solubility. It is still a goood idea to drink 8-10 glasses of water a day while taking it.
124
Sulfonamides :
ADME:
ADME:
Absorption: Well absorbed. (IV- PO)
Distribution: Well distributed (lungs/prostate/ high concentrations in urine)
Elimination: Renally
```
Drug interactions: CY450 Inhibitor (CYP2C9)
**Warfarin
Phenytoin
Some oral hypoglycemics
Fluoxetine (Prozac)
```
125
Combination: Trimethoprim:SMX (Bactrim/Cotrim)
MOA-
MOA- Inhibits consecutive steps in folic acid synthesis.
| ****Synergistic Combo!!!
126
Combination: Trimethoprim:SMX (Bactrim/Cotrim)
Spectrum-
```
Spectrum- Enhanced when compared to wither agent alone.
E.Coli
Proteus
Salmonella / Shigella
H.Flu
P.Carinii
Some Gram Positive (Even MRSA)
```
127
Combination: Trimethoprim:SMX (Bactrim/Cotrim)
Uses:
UTIs, Otitis, Bronchitis, Pneumonia, PCP
128
Name the Fluroquinolones
Drugs: Ciprofloxacin, LevoFloxacin, Moxifloxacin (And others)
129
Ciprofloxacin, LevoFloxacin, Moxifloxacin
MOA-
MOA- Inhibits DNA gyrase which converts circular DNA into supercoil structure. If we prevent the supercoil, replication cannot take place.
130
Ciprofloxacin, LevoFloxacin, Moxifloxacin
Spectrum- Bactericidal:
```
Spectrum- Bactericidal:
Most Gram Negative Rods
E.Coli
Klebs
Salmonella
Shigella
H.Flu
Pseudomonas
Gram Negative Cocci- Gonococcus, meningococcus
Gram Positive Pneumococcus
```
131
Ciprofloxacin, LevoFloxacin, Moxifloxacin
Pharmacokinetics:
Excellent Absorption rivals IV (IV ->PO)
| Excellent Distribution aside from CSF
132
Ciprofloxacin, LevoFloxacin, Moxifloxacin
Uses:
URI, UTI, Bones, Joints, and soft tissue.
133
Ciprofloxacin, LevoFloxacin, Moxifloxacin
ADE-
ADE-
CNS: Dizziness, confusion, psychosis, rarely seizures.
Tendon Rupture: Typically in the Achilles tendon. Disrupts cartilage stabilization. Generally CI in children less than 18 years old.
Photosensitivity
Drug Interactions -
Absorption impaired by cations (antacids, iron, calcium, and zinc) Administer quinolones 6 hours prior or 2 hours after.
Theophylline- increased levels due to CYP450 inhibition (Especially Cipro)
Warfarin- Increased Levels.
134
Metronidazole-
MOA-:
MOA-: Bactericidal to Anaerobes. Anaerobes take up the drug wich ultimately precipitates DNA strand Breakage.
135
Metronidazole-
therapeutic Uses:
Therapeutic Uses: Anaerobes
H.Pylori Surgical Procedures (Belly Bugs)
C-Diff Colitis (PO)
136
Metronidazole- Side Effects:
Side Effects: Disulfiram Reaction
Drug Interactions: Warfarin
137
Rifampin-
| MOA-
MOA- Inhibits RNA polymerase which inhibits protein synthesis
138
Rifampin- Spectrum-
Spectrum- Most Gram Positive Cocci and Gram Positive Rods like H.Flu. ** DO NOT USE as Mono Treatment due to development of rapid resistance.
139
Rifampin-
| Pharmacokinetics-
Pharmacokinetics- potent inducer of CPY450 (Warfarin / Phenytoin / Carbamazepine / oral contraceptives, Protease inhibitors, ect. )
140
Rifampin-
| Uses:
Uses:
Tuberculosis- in combo with other drugs
Meningococcus- highly effective for add on therapy with meningitis
Infections caused by staph epi and staph aureas- endocarditis, osteomylitis
141
Rifampin- ADE-
ADE-
Hepatoxicity- transaminase elevation approximately 14% of the time. Typically harmless.
Dislocation of body fluids- red orange dislocation of the urine, sweat, tears, can permanently stain contact lenses.
142
What are the Antibiotics that interfere with warfarin
```
Sulfonamides
Trimethoprim
Ciprofloxacin
Moxifloxacin
Metronidazole
Erythromycin
Azythromycin
Clarithromycin
Rifampin
```
