Brainscape's Knowledge GenomeTM

Browse over 1 million classes created by top students, professors, publishers, and experts.


See full index

Respiratory II > Overview of Antimicrobial Agents > Flashcards

Overview of Antimicrobial Agents Flashcards

1
Q

Anitmicrobial Classes

A

Penicillins

Cephalosporins

Carbapenems

Monobactams

B-lactamase Inhibitors

Glycopeptides

Fluoroquinolones

Aminoglycosides

Tetracyclines/Glycylcyclines

Macrolides/Ketolides

Lincosamides

Streptogramins

Oxazolidinones

Polymyxins

Lipopeptides

Metronidazole

Sulfonamides/Trimethoprim

Urinary Tract Antiseptics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

Penicillins

A

a) Natural Penicillins
i) Penicillin G (IV, IM)
ii) Penicillin V (PO)
b) Anti-staphylococcal Penicillins
i) Oxacillin (IV, IM)
ii) Dicloxacillin (PO)
iii) Nafcillin (IV, IM)
c) Aminopenicillins
i) Ampicillin (PO, IV, IM)*
ii) Amoxicillin (PO)*
d) Anti-pseudomonal Penicillins
i) Ticarcillin (IV)
ii) Piperacillin (IV)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Cephalosporins

A

a) First Generation
i) Cefazolin [Ancef] (IV, IM)
ii) Cephalexin [Keflex] (PO)
b) Second Generation
i) Cefoxitin [Mefoxitin] (IV)
ii) Cefuroxime (PO, IV, IM)
c) Third Generation
i) Ceftriaxone [Rocephin] (IV, IM)*
ii) Ceftazidime [Fortaz] (IV, IM)*
d) Fourth Generation
i) Cefepime (IV, IM)*

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

Carbapenems

A

Carbapenems

a) Imipenem/cilastatin [Primaxin] (IV)
b) Meropenem [Merrem] (IV)*
c) Ertapenem [Invanz] (IV, IM)*

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

Monobactams

A

Monobactams

a) Aztreonam [Azactam, Cayston] (IV, IM, INH)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

B-lactamase Inhibitors

A

B-lactamase Inhibitors

a) Ampicillin-sulbactam [Unasyn] (IV)*
b) Amoxicillin-clavulanic acid [Augmentin] (PO)*
c) Piperacillin-tazobactam [Zosyn] (IV)*

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

Glycopeptides

A

Glycopeptides

a) Vancomycin (PO, IV)*

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Fluoroquinolones

A

Fluoroquinolones

a) Ciprofloxacin [Cipro] (PO, IV, topical)
b) Levofloxacin [Levaquin] (PO, IV, topical)*
c) Moxifloxacin [Avelox] (PO, IV, topical)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Aminoglycosides

A

Aminoglycosides

a) Amikacin (IV, IM)
b) Tobramycin (IV, IM, INH, topical)
c) Gentamicin (IV, IM, topical)*

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Tetracyclines/Glycylcyclines

A

Tetracyclines/Glycylcyclines

a) Minocycline [Minocin] (PO, IV)
b) Doxycycline (PO, IV)*
c) Tigecycline [Tygacil] (IV)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

Macrolides/Ketolides

A

Macrolides/Ketolides

a) Clarithromycin [Biaxin] (PO)
b) Azithromycin [Zithromax, Z-pak] (PO, IV, topical)*
c) Telithromycin [Ketek] (PO)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

Lincosamides

A

Lincosamides

a) Clindamycin [Cleocin] (PO, IV, IM, topical)*

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

Streptogramins

A

Streptogramins

a) Quinipristin/dalfopristin (IV)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Oxazolidinones

A

Oxazolidinones

a) Linezolid [Zyvox] (PO, IV)*

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

Polymyxins

A

Polymyxins

a) Colistin (IV, IM, INH)
b) Polymyxin B (IV, topical, irrigation)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

Lipopeptides

A

Lipopeptides

a) Daptomycin [Cubicin] (IV)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
17
Q

Metronidazole

A

Metronidazole [Flagyl] (PO, IV, topical)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
18
Q

Sulfonamides/Trimethoprim

A

Sulfonamides/Trimethoprim

a) Sulfamethoxazole/trimethoprim [Bactrim] (PO, IV)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
19
Q

Urinary Tract Antiseptics

A

Urinary Tract Antiseptics

a) Methenamine (PO)
b) Nitrofurantoin (PO)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
20
Q

Microorganisms and Antimicrobials

A

Microorganisms and Antimicrobials

a) Clinically significant microorganisms generally fall into four categories: bacteria, viruses, fungi, and parasites. Initial classification of antimicrobials follows these broad categories:
i) Bacteria → antibacterial or antibiotic
ii) Viruses → antiviral
iii) Fungi → antifungal
iv) Parasites → antiparasitic
b) Antimicrobials are further classified based on the class and spectrum of microorganism it kills, the biochemical pathway it interferes with, and their chemical structure.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
21
Q

Determining Appropriate Antimicrobial Therapy

A

Determining Appropriate Antimicrobial Therapy

a) Antimicrobials are vastly overprescribed.
i) This facilitates resistance at a time when therapeutic options are becoming extremely limited.
b) One must determine whether an antimicrobial is indicated in specific clinical situations. Ask yourself the following questions to assess whether antimicrobials are warranted:
i) Is an antimicrobial indicated based on clinical findings?
ii) Have appropriate cultures been obtained?
iii) What is the likely causative organism?
iv) What must be done to prevent secondary exposure?
v) Is there clinical evidence or established guidelines that have determined antimicrobial therapy provides a clinical benefit?
c) Once the pathogen is known, one must always continue to question whether management is appropriate and optimized:
i) Would a narrower spectrum antimicrobial be more appropriate compared to the empiric regimen?
ii) Is one agent or a combination of agents necessary?
iii) Has the dose, route of administration, and duration of therapy been optimized?
iv) Have the most appropriate tests been completed (e.g., susceptibility)?
v) Are adjunctive measures also applicable (e.g., surgery to remove necrotic tissue)?

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
22
Q

Types and Goals of Antimicrobial Therapy

Prophylactic Therapy

A

Types and Goals of Antimicrobial Therapy

a) Types and goals of therapy differ based on disease progression
b) Prophylactic Therapy
i) Goal: prevent infection or prevent dangerous disease in those already infected.
ii) Examples: based on CD4 counts, antimicrobials are initiated in HIV infection (immunocompromised patient) to prevent opportunistic disease; post-exposure prophylaxis is provided to those who have been in contact with a patient with meningococcal meningitis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
23
Q

Typer and Goals of Antimicrobial Therapy

Preemptive Therapy

A

Preemptive Therapy

i) Goal: provide early, targeted antimicrobial therapy in high-risk patients who are currently asymptomatic but have become infected.
ii) Example: cytomegalovirus (CMV) treatment after stem cell and solid organ transplants.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
24
Q

Typer and Goals of Antimicrobial Therapy

Empiric Therapy

A

Empiric Therapy

i) Goal: provide antimicrobial therapy to a symptomatic patient without initial identification of infecting organism. Must consider knowledge of which microorganisms are most likely to cause specific infection/symptoms found in patient.
ii) Example: prescribing antimicrobials for community-acquired pneumonia (CAP) based on knowledge of most likely infecting pathogen.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
25
Q

Typer and Goals of Antimicrobial Therapy

Definitive Therapy

A

Definitive Therapy

i) Goal: infecting organism now known, antibiotics should be streamlined based on susceptibility and duration should be limited to appropriate length.
ii) Example: Staphylococcus aureus bacteremia treated empirically with vancomycin but susceptible to nafcillin, antimicrobials appropriately changed to most narrow spectrum antibiotic.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
26
Q

Types and Goals of Antimicrobial Therapy

Post-Treatment Suppressive Therapy

A

Post-Treatment Suppressive Therapy

i) Goal: continue lower dose, antimicrobial therapy when infection has not been completely eradicated and immunological or anatomical defect still present which lead to original infection.
ii) Example: orthopedic implant that has become infected but cannot be removed.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
27
Q

Susceptibility Testing

A

Susceptibility Testing

a) Most valuable, time tested method for immediate identification of bacteria = gram stain.
b) Once organism identified, must confirm whether the pathogen is susceptible to a given antimicrobial.
i) Minimum inhibitory concentration (MIC): lowest concentration of drug required to inhibit growth.
(1) Results are correlated with known drug concentrations in various body compartments.
(2) Susceptible, intermediate, or resistant interpretations are reported by the lab. [Definitions taken from the Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Susceptibility Testing: Twenty-Second Informational Supplement. CLSI document M100-S22 (ISBN 1-56238-785-5 [Print]; ISBN 1-56238-786-3 [Electronic]). Clinical and Laboratory Standards Institute, Wayne, Pennsylvania 19087 USA, 2012.]
(a) Susceptible (S): isolates are inhibited by usually achievable concentrations of antimicrobial when dose recommended to treat site of infection is used.
(b) Intermediate (I): antimicrobial MIC approaches usually attainable blood and tissue levels, and for which response rates may be lower than for susceptible isolates.
(c) Resistant (R): isolates are not inhibited by the usually achievable concentrations of antimicrobial, and/or MICs or zone diameters fall in the range where specific resistance mechanisms are likely, and clinical efficacy of the agent has not been reliably shown.
(3) Breakpoints established by Clinical and Laboratory Standards Institute (CLSI).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
28
Q

Susceptibility Testing

Dilution tests

A

Dilution tests

(1) Antibiotics used in broth medium in serially diluted concentrations.
(2) After 18-24 hours incubation, growth of organism is measured.
(3) MIC determined based on the lowest concentration of drug that inhibits visible growth. (4) Can use automated system: broth dilution & measure optical density to assess bacterial growth.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
29
Q

Susceptibility Testing

Disk diffusion

A

Disk diffusion

(1) Antibiotic containing disks on agar.
(2) Measure size of clear zone after 18-24 hours incubation.
(3) Standardized zone sizes for bacterial species to distinguish between susceptible and resistant.
(4) Only qualitative “susceptible” or “resistant”, no MIC value measured.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
30
Q

Susceptibility Testing

Optical diffusion

A

Optical diffusion

(1) Test strip with varying antibiotic concentrations placed on agar which shows clear elliptical zones to determine MIC.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
31
Q

Antibacterial Spectrum

A

Antibacterial Spectrum

a) Narrow-spectrum: act on a single or a limited group of microorganisms
b) Extended-spectrum: active against gram-positive bacteria but also significant number of gram-negative c) Broad-spectrum: act on a wide variety of bacterial species, including both gram-positive and -negative

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
32
Q

Bacteriostatic vs. Bactericidal Drugs

A

Bacteriostatic vs. Bactericidal Drugs

a) Bacteriostatic: arrests growth and replication of bacteria (limits spread of infection)
i) In general, bacterial protein synthesis inhibitors.
b) Bactericidal: kills bacterial
i) Concentration-dependent killing: rate & extent of killing increase with increasing concentrations
(1) Examples: aminoglycosides and fluoroquinolones
ii) Time-dependent killing: activity continues as long as serum concentration is above minimum bactericidal concentration
(1) Examples: B-lactams and vancomycin

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
33
Q

Antibacterial Targets:

A

Antibacterial Targets:

i) Cell wall synthesis
ii) Cell membrane synthesis
iii) Protein synthesis (30S and 50S ribosomal subunits) iv) Nucleic acid metabolism
v) Function of topoisomerases
vi) Folate synthesis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
34
Q

Bacterial Resistance

A

Bacterial Resistance

a) Two factors associated with development of antimicrobial resistance:
i) Evolution
ii) Clinical/environmental practices
b) Resistance Mechanisms
i) Reduced entry of antibiotic into pathogen
ii) Enhanced export of antibiotic by efflux pumps
iii) Release of microbial enzymes which destroy antibiotic
iv) Alteration of microbial proteins that transform pro- drugs to the effective moieties
v) Alteration of target proteins
vi) Development of alternative pathways to those inhibited by antibiotics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
35
Q

Bacterial Resistance Mechanisms

Beta-Lactams

A

Beta-Lactams

a) Compounds containing a four-membered lactam ring: penicillins, cephalosporins, monobactams, carbapenems, and B-lactamase inhibitors. These agents share features of chemistry, mechanism of action, pharmacology, and immunologic characteristics

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
36
Q

Bacterial Resistance Mechanisms Penicillins Basic structure:

A

Penicillins Basic structure: thiazolidine ring connected to a B-lactam ring, attached to a side-chain. Side-chains determine susceptibility to inactivating enzymes (B-lactamases), antibacterial activity, and pharmacologic properties.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
37
Q

Bacterial Resistance Mechanisms

Penicillins MOA:

A

Penicillins

MOA: inhibits the transpeptidation reaction, the last step in peptidoglycan synthesis. Cell wall composed of peptidoglycan which provides rigid mechanical stability. Peptidoglycan composed of two alternating sugars (N-acetylglucosamine and N-acetylmuramic acid). Five-amino-acid peptide linked to final N-acetylmuramic acid which terminates in D-alanyl-D-alanine. Penicillin binding proteins (PBPs) remove the terminal D-alanine in the process of forming the cross-link. B-lactams are structural analogs of D-Ala-D-Ala. B-lactams covalently bind the PBP active site preventing cross-linking, ultimately leading to cell autolysis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
38
Q

Bacterial Resistance Mechanisms Penicillins Bacterial resistance:

A

Penicillins Bacterial resistance: structural difference in PBPs, decreased PBP affinity for B-lactams, inability for drug to reach site of action (i.e. gram-negative organisms), active efflux pumps, drug destruction and inactivation by B-lactamases.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
39
Q

Bacterial Resistance Mechanisms

Penicillins classified based on their spectrum of activity:

A

Penicillins classified based on their spectrum of activity: i) Natural penicillins: highly effective against gram-positive cocci but easily hydrolyzed by penicillinase (B-lactamase).

(1) Penicillin G and penicillin V
(a) PK: penicillin G IM peak concentration 15-30 minutes; penicillin G benzathine absorbed more slowly with average duration of antimicrobial activity in plasma ~26 days.
(i) Reaches cerebrospinal fluid (CSF) when meninges inflamed
(ii) Eliminated in urine, 90% via tubular secretion, t1/2 30 minutes
(b) Therapeutic use: narrow-spectrum once sensitivity determined in Streptococcus pneumoniae pneumonia and meningitis. Penicillin V for Streptococcus pyogenes pharyngitis, toxic shock, viridians streptococci endocarditis if susceptible, syphilis (no alternative in pregnant women so if allergic they must be desensitized)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
40
Q

Bacterial Resistance Mechanisms

Penicillins classified based on their spectrum of activity:

Anti-staphylococcal penicillins:

A

Penicillins classified based on their spectrum of activity: Anti-staphylococcal penicillins: penicillinase resistant thus agents of first choice for Staphylococcus aureus and Staphylococcus epidermidis that are not methicillin resistant.

(1) Oxacillin, dicloxacillin, nafcillin
(a) PK: oxacillin and dicloxacillin – rapid GI absorption (30-80%), more efficient on an empty stomach (give 1 hour before or 2 hours after meals), peak concentration 1 hour.
(i) Rapidly excreted by kidney, t1/2 30-60 minutes
(b) PK: nafcillin – peak concentration 1 hour, 90% protein bound
(i) High concentration in bile, adequate concentration in CSF for Staphylococcus meningitis
(c) Therapeutic use: restricted to infections with known Staphylococcus sensitivity

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
41
Q

Bacterial Resistance Mechanisms Penicillins classified based on their spectrum of activity:

Aminopenicillins:

A

Penicillins classified based on their spectrum of activity: Aminopenicillins: extended-spectrum, frequently administered with a B-lactamase inhibitor, extends beyond gram-positive to gram-negative (Haemophilus influenzae, Escherichia coli, Proteus mirabilis), Listeria monocytogenes, susceptible meningococci, enterococci.

(1) Ampicillin (+/- sulbactam), amoxicillin (+/- clavulanic acid)
(a) PK: ampicillin – t1/2 80 minutes, removed by hemodialysis
(b) PK: amoxicillin – rapid and complete GI absorption, identical spectrum to ampicillin
(c) Therapeutic use: upper respiratory tract infections (S. pyogenes, S. pneumoniae, H. influenzae), sinusitis, otitis media, enterococcal infections

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
42
Q

Bacterial Resistance Mechanisms

Penicillins classified based on their spectrum of activity:

Anti-pseudomonal penicillins:

A

Penicillins classified based on their spectrum of activity: Anti-pseudomonal penicillins: extends spectrum to Pseudomonas aeruginosa, Enterobacter, and Proteus spp. Piperacillin superior for Pseudomonas, extends coverage to Klebsiella and anaerobes.

(1) Ticarcillin (+/- clavulanic acid), piperacillin (+/- tazobactam)
(a) PK: piperacillin/tazobactam commonly given as extended-infusion to maximize time-dependent killing. High biliary concentrations.
(b) Therapeutic use: serious gram-negative infections, hospital acquired pneumonia, immunocompromised patients, bacteremia, burn infections, urinary tract infection (UTI)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
43
Q

Bacterial Resistance Mechanisms -

Penicillins ADRs:

A

Penicillins

ADRs: generally well tolerated; most serious reactions due to hypersensitivity: allergic reactions (0.7-10%), anaphylaxis (0.004-0.04%), interstitial nephritis (rare); large, oral doses may cause nausea, vomiting, mild to severe diarrhea, pseudomembranous colitis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
44
Q

Bacterial Resistance Mechanisms

Cephalosporins MOA:

A

Cephalosporins MOA: inhibits the transpeptidation reaction, the last step in peptidoglycan synthesis. Cell wall composed of peptidoglycan which provides rigid mechanical stability. Peptidoglycan composed of two alternating sugars (N-acetylglucosamine and N-acetylmuramic acid). Five-amino-acid peptide linked to final N-acetylmuramic acid which terminates in D-alanyl-D-alanine. Penicillin binding proteins (PBPs) remove the terminal D-alanine in the process of forming the cross-link. B-lactams are structural analogs of D-Ala-D-Ala. B-lactams covalently bind the PBP active site preventing cross-linking, ultimately leading to cell autolysis.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
45
Q

Bacterial Resistance Mechanisms

Cephalosporins Resistance:

A

Cephalosporins Bacterial Resistance: structural difference in PBPs, decreased PBP affinity for B-lactams, inability for drug to reach site of action (i.e. gram-negative organisms), active efflux pumps, drug destruction and inactivation by B-lactamases.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
46
Q

Bacterial Resistance Mechanisms

Cephalosporins classified in generations based on general features of antimicrobial activity.

A

Cephalosporins classified in generations based on general features of antimicrobial activity.

i) None of the cephalosporins have activity against methicillin-resistant Staphylococcus aureus (MRSA), Listeria, or enterococci (exception ceftaroline with some enterococci activity).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
47
Q

Bacterial Resistance Mechanisms

Cephalosporins First-generation:

A

Cephalosporins First-generation: good gram-positive coverage, modest gram-negative (covers Moraxella, E. coli, Klebsiella pneumoniae, P. mirabilis), orally active anaerobes.

(1) Cefazolin, cephalexin
(a) PK: cefazolin – excreted by glomerular filtration, 85% plasma protein bound, t1/2 2 hours
(b) PK: cephalexin – 70-100% excreted in urine, not metabolized, t1/2 0.9 hours
(c) Therapeutic use: skin and soft tissue infections (SSTIs), surgical prophylaxis

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
48
Q

Bacterial Resistance Mechanisms

Cephalosporins Second-generation:

A

Cephalosporins Second-generation: somewhat increased activity against gram-negative, but less active than third-generation. Subset (cefoxitin, cefotetan) active against Bacteroides fragilis.

(1) Cefoxitin, cefuroxime
(a) PK: cefoxitin – t1/2 40 minutes
(b) PK: cefuroxime – t1/2 1.7 hours, can be given every 8 hours
(c) Therapeutic use: have been displaced by third-generation for many gram-negative infections, used in facultative gram-negative mixed anaerobic (intra-abdominal infections, pelvic inflammatory disease, diabetic foot infections)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
49
Q

Bacterial Resistance Mechanisms

Cephalosporins Third-generation:

A

Cephalosporins Third-generation: less active against gram-positive than first-generation, much more active against Enterobacteriaceae (although resistance increasing due to B-lactamase producing strains), ceftazidime covers P. aeruginosa.

(1) Ceftriaxone, ceftazidime
(a) PK: ceftriaxone – t1/2 8 hours, may be administered once or twice daily (twice daily in meningitis), half recovered in urine and half in bile
(b) PK: ceftazidime – t1/2 1.5 hours, not metabolized
(c) Therapeutic use: drug-of-choice (DOC) for serious gram-negative infections (Klebsiella, Proteus, Providencia, Serratia, Haemophilus); ceftriaxone DOC for all forms of gonorrhea and severe Lyme’s disease; meningitis; ceftazidime option for Pseudomonas

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
50
Q

Bacterial Resistance Mechanisms

Cephalosporins Fourth-generation:

A

Cephalosporins Fourth-generation: spectrum beyond third-generation, useful in serious infections in hospitalized patients, good activity against P. aeruginosa, Enterobacteriaceae, S. aureus, S. pneumoniae.

(1) Cefepime
(a) PK: cefepime – stable against hydrolysis by many B-lactamases, 100% renal excretion, excellent penetration to CSF, t1/2 2 hours
(b) Therapeutic use: empirical treatment of nosocomial infections

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
51
Q

Bacterial Resistance Mechanisms

Cephalosporins Fifth-generation:

A

Cephalosporins Fifth-generation: ceftaroline FDA approved 2010 with activity against gram-positive and gram-negative but with unique coverage of methicillin resistant S. aureus (MRSA).

(1) Ceftaroline
(a) Therapeutic use: skin and soft tissue infections, community-acquired pneumonia

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
52
Q

Bacterial Resistance Mechanisms

Cephalosporins ADRs:

A

Cephalosporins ADRs: 1% risk of cross-reactivity to penicillins (patients with true anaphylaxis to penicillin should not receive first- or second-generation cephalosporins); diarrhea, intolerance to alcohol (disulfram-like reaction due to N-methylthiotetrazole (MTT) group of cefotetan).

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
53
Q

Bacterial Resistance Mechanisms

Carbapenems MOA/Resistance:

A

Carbapenems MOA/Resistance: see penicillins, very resistant to hydrolysis until emergence of KPC carbapenemase.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
54
Q

Bacterial Resistance Mechanisms

Carbapenems Spectrum:

A

Carbapenems Spectrum: aerobic and anaerobic microorganisms, gram-positive (Streptococcus, enterococci, Staphylococcus, Listeria), excellent activity against Enterobacteriaceae, Pseudomonas, Acinetobacter. Stenotrophomonas maltophilia is resistant. Ertapenem inferior Pseudomonas & Acinetobacter activity.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
55
Q

Carbapenems PK: imipenem –

A

Carbapenems PK: imipenem – hydrolyzed rapidly by brush border of proximal renal tubule, active drug concentration in urine was low so combined with cilastatin which inhibits dehydropeptidase. t1/2 1 hr.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
56
Q

Carbapenems PK: meropenem –

A

Carbapenems PK: meropenem – does not require co-administration with cilastatin, not sensitive to dehydropeptidase

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
57
Q

Carbapenems PK: ertapenem –

A

Carbapenems PK: ertapenem – longer t1/2 which allows for once daily dosing

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
58
Q

Carbapenems Therapeutic use:

A

Carbapenems Therapeutic use: susceptible infections which are resistant to other available drugs; UTI, lower respiratory tract infection (LRTI), intra-abdominal, gynecological, SSTI, bone and joint infections.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
59
Q

Carbapenems ADRs:

A

Carbapenems ADRs: nausea/vomiting (1-20%), seizures (1.5%), hypersensitivity.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
60
Q

Monobactam MOA/Resistance:

A

Monobactam MOA: inhibits the transpeptidation reaction, the last step in peptidoglycan synthesis. Cell wall composed of peptidoglycan which provides rigid mechanical stability. Peptidoglycan composed of two alternating sugars (N-acetylglucosamine and N-acetylmuramic acid). Five-amino-acid peptide linked to final N-acetylmuramic acid which terminates in D-alanyl-D-alanine. Penicillin binding proteins (PBPs) remove the terminal D-alanine in the process of forming the cross-link. B-lactams are structural analogs of D-Ala-D-Ala. B-lactams covalently bind the PBP active site preventing cross-linking, ultimately leading to cell autolysis.

Resistance: structural difference in PBPs, decreased PBP affinity for B-lactams, inability for drug to reach site of action (i.e. gram-negative organisms), active efflux pumps, drug destruction and inactivation by B-lactamases.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
61
Q

Monobactam Spectrum & PK

A

Spectrum: activity against aerobic gram-negatives (Enterobacteriaceae, Pseudomonas, H. influenzae, gonococci), no activity against gram-positive cocci (GPC) or anaerobes.

PK: t1/2 1.7 hours, most recovered in urine

62
Q

Monobactam Therapeutic use:

A

Monobactam Therapeutic use: patients who are allergic to penicillins and cephalosporins appear not to react to aztreonam, thus effective in treating gram-negative infections which would usually be treated with B-lactam if it were not for a history of prior allergic reaction.

63
Q

Glycopeptides MOA:

A

Glycopeptides MOA: inhibits cell wall synthesis binding with high affinity to D-alanyl-D-alanine terminal of cell wall precursor units. Due to large size, unable to penetrate outer membrane of gram-negative bacteria.

64
Q

Glycopeptides Bacterial resistance:

A

Glycopeptides Bacterial resistance: alteration of D-alanyl-D-alanine target to D-alanyl-D-lactate or D-alanyl-D-serine which binds glycopeptides poorly. Intermediate resistance may occur if small proportion of cells growing with vancomycin present or if they have abnormally thick cell wall.

65
Q

Glycopeptides Spectrum:

A

Glycopeptides Spectrum: broad gram-positive coverage: S. aureus (including MRSA), S. epidermidis (including MRSE), Streptococci, Bacillus, Corynebacterium spp, Actinomyces, Clostridium; all gram-negative and mycobacterium resistant.

66
Q

Glycopeptides PK:

A

Glycopeptides PK: vancomycin – poorly absorbed after oral administration, given IV (never IM), 30% protein bound, appears in CSF when meninges inflamed, bile, pleural, pericardial, synovial, ascetic fluid

i) 90% excreted by glomerular filtration, t1/2 ~6 hours, accumulates in renal failure (dose adjust)

67
Q

Glycopeptides Therapeutic use:

A

Glycopeptides Therapeutic use: osteomyelitis, endocarditis, MRSA, Streptococcus, enterococci, CNS infections, bacteremia, orally for Clostridium difficile.

i) Monitor serum drug concentrations (within 30 minutes prior to next scheduled dose) at steady state (typically before 4th dose). Target trough 15-20 mcg/mL for endocarditis, osteomyelitis, meningitis, MRSA pneumonia. Target trough 10-15 mcg/mL for SSTIs.

68
Q

Glycopeptides ADRs:

A

Glycopeptides ADRs: macular skin rash, chills, fever, rash. Red-man syndrome due to rapid infusion: extreme flushing, tachycardia, hypotension; not an allergic reaction, direct toxic effect of vancomycin on mast cells causing them to release histamine. Ototoxicity, nephrotoxicity (33% with initial trough > 20 mcg/mL).

69
Q

Fluoroquinolones MOA:

A

Fluoroquinolones MOA: concentration-dependent killing, targets bacterial DNA gyrase and topoisomerase IV. DNA must be separated to permit DNA replication or transcription, anything that separates strands leads to over-winding or excessive positive supercoiling. DNA gyrase is responsible for continuous introduction of negative supercoils.

70
Q

Fluoroquinolones Bacterial resistance:

A

Fluoroquinolones Bacterial resistance: mutation in bacterial chromosome genes encoding DNA gyrase or topoisomerase IV or by active transport out of cell. No FQ modifying or inactivating activities have been found.

71
Q

Fluoroquinolones Spectrum:

A

Fluoroquinolones Spectrum: E. coli, Salmonella, Shigella, Enterobacter, Campylobacter, Neisseria, P. aeruginosa (ciprofloxacin most active agent in this class against gram-negatives and particularly P. aeruginosa), S. aureus (not MRSA), atypicals (e.g. mycoplasmas and chlamydiae), intracellular pathogens (e.g. Legionella, mycobacteria), limited coverage of Streptococcus spp. Levofloxacin, moxifloxacin “respiratory fluoroquinolones” cover Streptococcus spp.

72
Q

Fluoroquinolones PK:

A

Fluoroquinolones PK: well absorbed, divalent/trivalent cations impair absorption, distributed widely.

i) Distribute to urine, kidney, prostate, lung, stool, bile, macrophages and neutrophils.
ii) Cleared by the kidney, needs dose adjustments in renal impairment with the exception of moxifloxacin (metabolized in liver).

73
Q

Fluoroquinolones Therapeutic use:

A

Fluoroquinolones Therapeutic use: UTI (FQ more effective than trimethoprim/sulfamethoxazole), prostatitis; STI (chlamydia, Neisseria gonorrhoeae) but ceftriaxone DOC for gonorrhea; traveler’s diarrhea, shigellosis; bone, joint, SSTI infections; diabetic foot infections; prophylaxis in neutropenic patients.

i) Respiratory FQs: S. pneumoniae, H. influenzae, Moraxella, S. aureus, M. pneumoniae, C. pneumoniae, Legionella
ii) Ciprofloxacin: Pseudomonas

74
Q

Fluoroquinolones ADRs:

A

Fluoroquinolones ADRs: generally well tolerated; GI 3-17% most common (mild nausea, vomiting, abdominal discomfort); CNS 0.9-11% (mild headache, dizziness, delirium, rare hallucinations); rash, photosensitivity, Achilles tendon rupture (CI in children).

75
Q

Amino glycosides MOA:

A

Amino glycosides MOA: concentration-dependent, binds 30S ribosomal subunit and disrupts normal cycle of ribosomal function by interfering with initiation of protein synthesis. Abnormal initiation complexes and aberrant proteins (due to misreading of mRNA template) accumulate. Aberrant proteins inserted into cell membrane lead to altered permeability.

i) AGs reach site of action via diffusion through porin proteins in outer cell membrane of gram-negative bacteria and electron transport/oxygen dependent movement across cytoplasmic membrane. (Cell wall active drugs may enhance AG transport = synergism)
ii) AGs also exhibit a post-antibiotic effect (PAE) – residual bactericidal activity persists after serum concentration is lower than MIC.

76
Q

Amino glycosides Bacterial resistance:

A

Amino glycosides Bacterial resistance: AG metabolizing enzymes, impaired transport of drug into cell, altered ribosome.

77
Q

Amino glycosides Spectrum:

A

Aminoglycosides Spectrum: aerobic gram-negative bacteria, limited action against gram-positive, produces synergistic bactericidal effects in gram-positive when combined with a cell wall active agent (B-lactam or vancomycin).

i) Kanamycin more limited – do not use for Serratia or P. aeruginosa
ii) Tobramycin – more active against P. aeruginosa and some Proteus
iii) Gentamicin – more active against Serrate

78
Q

Amino glycosides PK:

A

Aminoglycosides PK: highly polar, < 1% absorbed if given orally, volume of distribution approximates volume of extracellular fluid, poor distribution into adipose tissue, excreted by glomerular filtration, excretion directly proportional to creatinine clearance.

i) Low concentrations in tissues and secretions with the exception of renal cortex, endolymph, & perilymph of inner ear -> high concentrations likely contribute to nephrotoxicity and ototoxicity
ii) Tobramycin: may be given via inhalation in cystic fibrosis (CF) -> high sputum concentration and low serum concentration.
iii) Traditionally given as 2-3 divided doses based on short t1/2 2-3 hours, higher doses at extended-intervals likely to be equally efficacious and potentially less toxic.
iv) Gentamicin, tobramycin – peak: 4-10 mcg/mL, trough: < 1-2 mcg/mL
v) Amikacin, streptomycin – peak: 15-30 mcg/mL, trough: < 10 mcg/mL

79
Q

Amino glycosides Therapeutic use:

A

Amino glycosides Therapeutic use: UTI (not uncomplicated), used when there is resistance to other agents or in seriously ill patients, pneumonia (infective against S. pneumoniae and anaerobes), hospital-acquired pneumonia, peritonitis associated with peritoneal dialysis, synergy in bacterial endocarditis, tobramycin inhalation in CF, amikacin used when resistance to gentamicin and tobramycin high.

80
Q

Amino glycosides ADRs:

A

Amino glycosides ADRs: ototoxicity (as high as 25%), nephrotoxicity (8-26%), neuromuscular block and apnea.

81
Q

Tetracyclines & Glycylcyclines MOA:

A

Tetracyclines & Glycylcyclines MOA: bacteriostatic, inhibits bacterial protein synthesis by binding 30S bacterial ribosome and preventing access of aminoacyl tRNA to acceptor (A) site on mRNA ribosome complex (prevents addition of amino acids to growing peptide).

i) Enters outer membrane via passive diffusion through porin proteins and cytoplasmic membrane via active/energy-dependent transport.

82
Q

Tetracyclines & Glycylcyclines MOA:

A

Tetracyclines & Glycylcyclines MOA: bacteriostatic, inhibits bacterial protein synthesis by binding 30S bacterial ribosome and preventing access of aminoacyl tRNA to acceptor (A) site on mRNA ribosome complex (prevents addition of amino acids to growing peptide).

i) Enters outer membrane via passive diffusion through porin proteins and cytoplasmic membrane via active/energy-dependent transport.

83
Q

Tetracyclines & Glycylcyclines Bacterial resistance:

A

Tetracyclines & Glycylcyclines Bacterial resistance: decreased influx, acquisition of energy dependent efflux, ribosomal protection proteins, enzymatic inactivation.

84
Q

Tetracyclines & Glycylcyclines Spectrum:

A

Tetracyclines & Glycylcyclines Spectrum: wide range of aerobic and anaerobic gram-positive and gram-negative activity as well as effective for: Rickettsia, Coxiella burnetii, Mycoplasma pneumoniae, Chlamydia spp, Legionella, atypical mycobacterium, Plasmodium, Borrelia burgdorferi (Lyme’s disease), Treponema pallidum (syphilis).

i) Others: Bacillus anthracis, L. monocytogenes, MRSA, H. influenzae, Helicobacter pylori
ii) All strains of Pseudomonas resistant
iii) Tigecycline: equally or more active in vitro against bacteria than tetracyclines but does not cover Pseudomonas, Proteus, and Providencia

85
Q

Tetracyclines & Glycylcyclines PK:

A

Tetracyclines & Glycylcyclines PK: incomplete oral absorption, empty stomach absorbed tetracycline (60-80%), doxycycline (95%), minocycline (100%), absorption impaired when given concurrently with divalent and trivalent cations (Ca2+, Mg2+, Al3+, Fe2+/3+, Zn2+).

i) Distributes widely throughout body, urine and prostate, CNS, accumulates in liver, spleen, bone marrow, and in bone, dentine, and enamel of unerupted teeth
ii) Renal elimination but also concentrates in liver and excreted in bile. No adjustments required in renal impairment
iii) Tetracycline: t1/2 6-12 hours, administered 2-4x daily
iv) Doxycycline and minocycline: t1/2 16-18 hours, 90-100% absorbed. Minocycline extensively metabolized

86
Q

Tetracyclines & Glycylcyclines Therapeutic use:

A

Tetracyclines & Glycylcyclines Therapeutic use: CAP, atypical CAP coverage, community acquired SSTIs, community acquired MRSA, acne, Rickettsial infections (Rocky Mountain Spotted Fever), Q fever, anthrax, used in combination with other antimicrobials for H. pylori, plague, tularemia, and brucellosis.

i) Tigecycline – very broad spectrum with activity against coagulase-negative staphylococci, S. aureus (including MRSA, vancomycin-intermediate, and vancomycin-resistant strains), streptococci (penicillin-sensitive and resistant), enterococci (including vancomycin-resistant), gram-positive rods, Enterobacteriaceae, Acinetobacter spp., anaerobes. P. aeruginosa and Proteus resistant.

87
Q

Tetracyclines & Glycylcyclines ADRs:

A

Tetracyclines & Glycylcyclines ADRs: GI (epigastric burning, abdominal discomfort, nausea, vomiting, diarrhea), superinfections of C. difficile, photosensitivity, teeth (discoloration), thrombophlebitis

88
Q

Macrolides & Ketolides MOA:

A

Macrolides & Ketolides MOA: bacteriostatic, binds reversibly to 50S ribosomal subunit, inhibits translocation where a newly synthesized peptidyl tRNA molecule moves from acceptor site on ribosome to peptidyl donor site.

89
Q

Macrolides & Ketolides Bacterial resistance:

A

Macrolides & Ketolides Bacterial resistance: drug efflux, ribosomal protection proteins, hydrolysis, ribosomal mutations.

90
Q

Macrolides & Ketolides Spectrum:

A

Macrolides & Ketolides Spectrum: aerobic gram-positive cocci (GPCs) and bacilli; Staphylococcus not reliably susceptible.

i) Clostridium perfringens, Corynebacterium diphtheria, L. monocytogenes
ii) Inactive against most gram-negative bacteria, modest activity against H. influenzae, N. meningitides, N. gonorrhoeae, Pasteurella multocida, Borrelia spp, Bordetella pertussis, M. pneumoniae, Legionella pneumophilia, C. trachomatis, some atypical mycobacterium

91
Q

Macrolides & Ketolides PK: clarithromycin

A

Macrolides & Ketolides PK: clarithromycin – rapid absorption from GI tract, first-pass metabolism reduces bioavailability to 50-55%, peak 2 hours, liver metabolism to active metabolite 14-hydroxyclarithromycin, eliminated renally, t1/2 of parent 3-7 hours, t1/2 of metabolite 5-9 hours, dose adjust if CrCl

92
Q

Macrolides & Ketolides PK: azithromycin

A

Macrolides & Ketolides PK: azithromycin – absorbed rapidly, wide distribution (except CNS), administration of aluminum and magnesium hydroxide antacids reduces absorption, high intracellular concentration, hepatic metabolism to inactive metabolites, biliary excretion major route of elimination, t1/2 40-68 hours

93
Q

Macrolides & Ketolides Therapeutic use:

A

Macrolides & Ketolides Therapeutic use: respiratory tract infections (due to coverage of S. pneumoniae, H. influenzae, and atypicals: Mycoplasma, Chalmydophilia, Legionella), alternative for otitis media, sinusitis, bronchitis, and SSTIs. Pertussis, gastroenteritis, H. pylori, Mycobacterial infections.

94
Q

Macrolides & Ketolides ADRs:

A

Macrolides & Ketolides ADRs: GI (epigastric distress), hepatotoxicity, arrhythmia, QT prolongation.

95
Q

Macrolides & Ketolides DDIs:

A

Macrolides & Ketolides DDIs: CYP3A4 inhibition – prolongs effects of digoxin, valproate, warfarin, others.

i) Azithromycin structure differs making it less likely to produce DDIs but should use caution.

96
Q

Lincosamides MOA:

A

Lincosamides MOA: binds exclusively to 50S subunit of bacterial ribosome and suppresses protein synthesis.

97
Q

Lincosamides Bacterial resistance:

A

Lincosamides Bacterial resistance: ribosomal methylation.

98
Q

Lincosamides Spectrum:

A

Lincosamides Spectrum: pneumococci, S. pyogenes, viridans Streptococci, MSSA, anaerobes (B. fragilis).

i) All aerobic gram-negative bacilli are resistant.

99
Q

Lincosamides PK:

A

Lincosamides PK: clindamycin – t1/2 2.9 hours, nearly completely absorbed, peak concentration 1 hour, 90% protein bound, accumulates in polymorphonuclear leukocytes, alveolar macrophages, abscesses, 10% excreted unchanged in the urine, inactivated by hepatic metabolism (must dose adjust in hepatic failure)

100
Q

Lincosamides Therapeutic use:

A

Lincosamides Therapeutic use: SSTIs, necrotizing SSTIs, penetrating wounds, lung abscesses, anaerobic lung and pleural space infections, topically for acne vulgaris.

101
Q

Lincosamides ADRs:

A

Lincosamides ADRs: GI diarrhea (2-20%), pseudomembranous colitis (0.01-10%) due to C. difficile, skin rashes (10%), reversible increase in aminotransferase activity, may potentiate neuromuscular blockade.

102
Q

Streptogramins MOA:

A

Streptogramins MOA: bactericidal, protein synthesis inhibitors, bind 50S ribosomal subunit.

Quinpristin (streptogramin B) binds same site as macrolides which inhibits polypeptide elongation and causes early termination of protein synthesis.

Dalfopristin (streptogramin A) binds site nearby resulting in conformational change in 50S ribosome, synergistically enhancing binding of quinipristin.

103
Q

Streptogramins Bacterial resistance:

A

Streptogramins Bacterial resistance: ribosomal methylase, acetyltransferase inactivation of dalfopristin.

104
Q

Streptogramins Spectrum:

A

Streptogramins Spectrum: GPCs including S. pneumoniae, B and α hemolytic Streptococcus, E. faecium (not E. faecalis), and coagulase-positive and negative Staphylococcus.

i) Largely inactive against gram-negatives, but Moraxella catarrhalis and Neisseria susceptible
ii) Active against atypical organisms (M. pneumoniae, Legionella spp, C. pneumoniae)
iii) Bactericidal against Streptococcus and many strains of Staphylococcus, static against E. faecium

105
Q

Streptogramins PK:

A

Streptogramins PK: only given IV in a combination quinipristin:dalfopristin in 30:70 ratio, incompatible in saline and heparin → must be dissolved in dextrose 5% in water. i) t1/2 0.85 hours for quinispristin, 0.7 hours dalfopristin, hepatic metabolism, 80% biliary excretion.

106
Q

Streptogramins Therapeutic use:

A

Streptogramins Therapeutic use: vancomycin resistant E. faecium (VRE) and complicated SSTI by MSSA or S. pyogenes.

107
Q

Streptogramins ADRs:

A

Streptogramins ADRs: infusion related pain and phlebitis, arthralgia and myalgia.

108
Q

Streptogramins DDIs:

A

Streptogramins DDIs: inhibits CYP3A4 – affects anticonvulsants, macrolides, some FQs (moxifloxacin), antidepressants, warfarin, non-nucleoside reverse transcriptase inhibitors.

109
Q

Oxazolidinones MOA:

A

Oxazolidinones MOA: inhibits protein synthesis binding P site of 50S ribosomal subunit, prevents formation of larger ribosomal fmet-tRNA complex which initiates protein synthesis.

110
Q

Oxazolidinones Bacterial resistance:

A

Oxazolidinones Bacterial resistance: ribosomal mutation.

111
Q

Oxazolidinones Spectrum:

A

Oxazolidinones Spectrum: gram-positive Staphylococcus (MSSA, MRSA, VRSA), Streptococcus (penicillin resistant S. pneumoniae), enterococci (vancomycin-resistant E. faecium, VRE), gram-positive anaerobic cocci, gram-positive rods (Corynebacterium, L. monocytogenes).

i) Poor activity against gram-negative aerobic and anaerobic bacteria
ii) Bacteriostatic against enterococci and Staphylococcus and bactericidal against Streptococcus

112
Q

Oxazolidinones PK:

A

Oxazolidinones PK: linezolid – well absorbed orally, bioavailability 100%, t1/2 4-6 hours, 30% protein bound, distributes widely to well perfused tissues.

113
Q

Oxazolidinones Therapeutic use:

A

Oxazolidinones Therapeutic use: VRE faecium (SSTI, UTI, bacteremia); nosocomial pneumonia caused by MSSA and MRSA; CAP; complicated SSTI infections, uncomplicated SSTIs

i) Because linezolid is bacteriostatic against enterococci and Staphylococcus → should not be used as first-line for suspected endocarditis.
ii) DO NOT use when other agents are likely to be effective, should be reserved for multiple-drug resistant organisms.

114
Q

Oxazolidinones ADRs:

A

Oxazolidinones ADRs: myelosuppression [thrombocytopenia (2.4%), anemia, leukopenia, pancytopenia], minor GI complaints, headache, rash.

115
Q

Oxazolidinones DDIs:

A

Oxazolidinones DDIs: weak, nonspecific inhibitor of monoamine oxidase, concomitant adrenergic or serotonergic (selective-serotonin reuptake inhibitors, SSRI’s) may lead to serotonin syndrome (palpitations, headache, hypertensive crisis). Avoid interaction if possible; however, short-term use (10-14 days) with careful monitoring is reasonable.

116
Q

Polymyxins MOA:

A

Polymyxins MOA: interacts with phospholipids, disrupts the structure of cell membranes, alters permeability.

117
Q

Polymyxins Spectrum:

A

Polymyxins Spectrum: restricted to gram-negative bacteria – Enterobacter, E. coli, Klebsiella, Salmonella, Pasteurella, Bordetella, and Shigella, P. aeruginosa, Acinetobacter (Proteus and Serratia resistant).

118
Q

Polymyxins PK:

A

Polymyxins PK: colistin (polymyxin E) and polymyxin B (topical), not absorbed orally, poorly absorbed from mucous membranes and surfaces of large burns, cleared renally, dose modification necessary in renal impairment.

119
Q

Polymyxins Therapeutic use:

A

Polymyxins Therapeutic use: topical, skin, mucous membranes, eye, ear, urinary bladder irrigation, inhalation.

120
Q

Polymyxins ADRs:

A

Polymyxins ADRs: no systemic effects for polymyxin B, polymyxin E is nephrotoxic → avoid with AGs, can cause muscle weakness and apnea due to interference with neurotransmission.

121
Q

Lipopeptides MOA:

A

Lipopeptides MOA: binds bacterial membranes resulting in depolarization, loss of membrane potential, cell death.

122
Q

Lipopeptides Bacterial resistance:

A

Lipopeptides Bacterial resistance: not fully described, may be due to changes in cell membrane charge.

123
Q

Lipopeptides Spectrum:

A

Lipopeptides Spectrum: bactericidal, concentration-dependent, active against aerobic, facultative and anaerobic gram-positive bacteria (Staphylococcus, MRSA, Streptococcus, enterococci, Corynebacterium, Peptostreptococcus, Clostridium perfringens).

124
Q

Lipopeptides PK:

A

Lipopeptides PK: daptomycin poorly absorbed orally, only administered IV, direct toxicity to muscle if given IM, reversibly bound to albumin 92%, t1/2 8-9 hours, once daily dosing. 80% recovered in urine, dose adjust for CrCl < 30 mL/min.

i) Penetrates lung adequately but inactivated by pulmonary surfactant

125
Q

Lipopeptides Therapeutic use:

A

Lipopeptides Therapeutic use: complicated SSTIs, complicated bacteremia, right sided endocarditis.

126
Q

Lipopeptides ADRs:

A

Lipopeptides ADRs: musculoskeletal damage, elevations in creatine kinase, rare rhabdomyolysis.

127
Q

Lipopeptides DDIs:

A

Lipopeptides DDIs: no CYP interactions, no other important DDIs but caution with AGs (additive nephrotoxicity)and statins (additive myopathy).

128
Q

Metronidazole MOA:

A

Metronidazole MOA: prodrug, requires reductive activation of nitro groups by susceptible organisms. Single electron transfer in anaerobic bacteria forms highly reactive nitro radical anions, kills organisms by radically mediated mechanisms that target DNA. Catalytically recycled. Increasing 02 inhibits metronidazole toxicity as 02 competes for electrons.

129
Q

Metronidazole Bacterial resistance:

A

Metronidazole Bacterial resistance: not well described, but due to decreased formation of nitro radicals.

130
Q

Metronidazole Spectrum:

A

Metronidazole Spectrum: All anaerobic cocci and both anaerobic gram-negative bacilli (including Bacteroides) and anaerobic spore forming gram-positive bacilli (Clostridium), trichomoniasis, amebiasis, giardiasis. Helicobacter and Campylobacter.

131
Q

Metronidazole PK:

A

Metronidazole PK: absorbed completely and rapidly after oral administration, t1/2 8 hours, penetrates well into body tissues and fluids, vaginal secretions, saliva, breast milk and CSF, does not cross placenta.

i) 75% eliminated in urine largely as metabolites, liver main site of metabolism accounts for > 50% of systemic Cl.

132
Q

Metronidazole Therapeutic use:

A

Metronidazole Therapeutic use: bacterial vaginosis, amebic liver abscess, treatment of anaerobic bacterial infections due to Bacteroides, Clostridium, Fusobacterium, Peptococcus, Peptostreptococcus, and Helicobacter. Clinically effective levels in bone, joints, and CNS. Part of regimen for prophylaxis of colorectal surgery. Clostridium difficile, Crohn’s disease.

133
Q

Metronidazole ADRs:

A

Metronidazole ADRs: headache, nausea, dry mouth, metallic taste. Vomiting, diarrhea, abdominal distress occasionally. Neurotoxic: dizziness, vertigo, very rarely encephalopathy. Well-reported disulfiram effect → abdominal distress, vomiting, flushing, headache, if alcohol consumed during/within 3 days of drug.

134
Q

Metronidazole DDIs:

A

Metronidazole DDIs: induced metabolism of phenobarbital, prednisone, rifampin. Prolongs prothrombin time in those receiving warfarin. Metabolism inhibited by cimetidine.

135
Q

Sulfonamides &Trimethoprim MOA:

A

Sulfonamides &Trimethoprim MOA: sulfonamides are bacteriostatic, competitive inhibitors of dihyropteroate synthase. This enzyme is responsible for incorporation of para-aminobenzoic acid (PABA) into dihydropteroic acid, the immediate precursor to folic acid. Prevents bacterial use of PABA for synthesis of folic acid. Synergistic trimethoprim, inhibits microbial dihydrofolate reductase, the enzyme which reduces dihydrofolate to tetrahydrofolate. This reduced form of folic acid is required for one-carbon transfer reactions. Simultaneous administration of a sulfonamide + trimethoprim introduces sequential blocks in pathway.

136
Q

Sulfonamides & Trimethoprim Bacterial resistance:

A

Sulfonamides & Trimethoprim Bacterial resistance: lower affinity of enzymes to drug binding, decreased bacterial permeability or active efflux, alternative pathway for essential metabolite synthesis, increased production of essential metabolite.

137
Q

Sulfonamides & Trimethoprim Spectrum:

A

Sulfonamides & Trimethoprim Spectrum: Chlamydia diphtheriae, N. menigitidis, S. aureus, S. epidermidis, S. pyogenes, viridans group Streptococcus, E. coli, Proteus mirabilis, Proteus morgannii, Enterobacter, Salmonella, Shigella, Serratia, Klebsiella, Brucella abortus, Pasteurella haemolytica, Yersinia pseudotuberculosis, T. enterocolitical, Norcardia asteroids.

138
Q

Sulfonamides & Trimethoprim PK:

A

Sulfonamides & Trimethoprim PK: formulated in 5:1 mg ratios of sulfamethoxazole:trimethoprim, trimethoprim 20-100x more potent than sulfamethoxazole, achieves 20:1 concentrations of SMX:TMP. t1/2 of SMX 10 hours, TMP 11 hours. SMX 25-50% excreted in urine in 24 hours, TMP 60%.

139
Q

Sulfonamides & Trimethoprim Therapeutic use:

A

Sulfonamides & Trimethoprim Therapeutic use: UTI, bacterial prostatitis, bronchitis, Shigellosis, Traveler’s diarrhea, Salmonella, Pneumocystis jiroveci (fungus) prophylaxis in neutropenia, Nocardia, Stenotrophomonas maltophilia, do NOT use in Streptococcus pharyngitis.

140
Q

Sulfonamides & Trimethoprim ADRs:

A

Sulfonamides & Trimethoprim ADRs: allergic skin rashes, nausea, vomiting, CNS (headache, depression), photosensitivity, renal dysfunction, Stevens-Johnson syndrome.

141
Q

Sulfonamides & Trimethoprim DDIs:

A

Sulfonamides & Trimethoprim DDIs: potentiates the effects of warfarin!

142
Q

Methenamine MOA:

A

Methenamine MOA: decomposes in water to formaldehyde, acidification of urine promotes formaldehyde formation, slow process (requires 3 hours to complete).

143
Q

Methenamine Bacterial resistance: no resistance.

A

Methenamine Bacterial resistance: no resistance.

144
Q

Methenamine Spectrum:

A

Methenamine Spectrum: nearly all bacteria are susceptible to formaldehyde.

145
Q

Methenamine PK:

A

Methenamine PK: 10-30% decomposition in gastric juice unless protected by enteric coating, ammonia produced so CI in hepatic insufficiency.

146
Q

Methenamine Therapeutic use:

A

Methenamine Therapeutic use: not primary drug for acute UTI, but has value in chronic suppressive therapy.

147
Q

Methenamine ADRs:

A

Methenamine ADRs: GI distress, painful and frequent micturition, albuminuria, hematuria, rashes, low systemic toxicity at usual doses.

148
Q

Nitrofurantoin MOA:

A

Nitrofurantoin MOA: drug reduced forming highly reactive intermediates which damage DNA, bacteria reduce drug more rapidly than mammalian cells, thought to account for selective activity.

149
Q

Nitrofurantoin PK:

A

Nitrofurantoin PK: absorbed rapidly and completely, macro-crystalline formulation absorbed and excreted more slowly, antibacterial concentration in plasma not found due to rapid elimination (plasma t1/2 0.3-1 hours), rate of excretion related to CrCl.

150
Q

Nitrofurantoin Therapeutic use:

A

Nitrofurantoin Therapeutic use: UTI, not recommended for pyelonephritis or prostatitis.

151
Q

Nitrofurantoin ADRs:

A

Nitrofurantoin ADRs: nausea, vomiting, diarrhea, macro-crystalline prep better tolerated. Course of therapy should not exceed 14 days and repeated course should be separated by rest periods.

i) CI: pregnant women, impaired renal function (40 mL/min), children

Respiratory II (14 decks)

Brainscape helps you reach your goals faster, through stronger study habits.
© 2024 Bold Learning Solutions. Terms and Conditions