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Antibiotics Flashcards

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1
Q

What class of antibiotics does Clindamycin belong to?

A

Lincosamide (related to macrolide)

Clindamycin is related to the macrolide class of antibiotics.

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2
Q

What is the primary mechanism of action of Clindamycin?

A

Protein synthesis inhibitor

Clindamycin is known to limit exotoxin production.

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3
Q

How does Clindamycin affect outcomes in Toxic Shock caused by Strep pyogenes?

A

Improves outcomes

Clindamycin is effective in managing Toxic Shock related to Strep pyogenes.

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4
Q

Is Clindamycin well absorbed in the body?

A

Yes

Clindamycin is a good option for skin and soft tissue infections if the bacteria are susceptible.

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5
Q

In which pediatric conditions is Clindamycin increasingly supported for effectiveness?

A
  • Pneumonia
  • Empyema
  • Bone/joint MRSA infections

Literature supports Clindamycin’s use in these pediatric infections.

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6
Q

What type of resistance is associated with Clindamycin?

A

Resistance mediated by the same gene as erythromycin

This resistance occurs via target site modification of the ribosomal binding site.

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7
Q

What risk is associated with erythromycin-resistant bacteria?

A

Inducible clindamycin resistance

If a bacteria is erythromycin-resistant, there is a risk of developing inducible resistance to clindamycin.

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8
Q

Fill in the blank: Clindamycin is known to limit _______ production.

A

exotoxin

Clindamycin’s inhibition of exotoxin production helps in treating certain infections.

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9
Q

True or False: Clindamycin is ineffective against severe S. aureus infections.

A

False

Clindamycin has a similar effect in severe S. aureus infections.

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10
Q

What types of infections is Doxycycline not recommended for?

A

Complicated or serious infections

Doxycycline should not be used for endovascular infections.

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11
Q

What are the common side effects of Doxycycline?

A
  • Photosensitivity
  • Oesophageal irritation
  • Enamel stain

Enamel staining is more pronounced when comparing tetracycline to doxycycline.

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12
Q

Beta-lactam antibiotics

A

Penicillins, Cephalosporins, Carbapenems, Monobactams

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13
Q

Mechanism of action of beta lactam antibiotics

A

Interfere with cell wall synthesis

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14
Q

Glycopeptide antibiotic

A

Vancomycin

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15
Q

Mechanism of action of Vancomycin

A

Interfere with cell wall synthesis, binds to D-Alanyl-D-Alanine and prevents cross linking

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16
Q

Antibiotics that interfere with nucleic acid synthesis

A

Sulfonamides, Trimethoprim, Quinolones, Rifampicin

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17
Q

Antibiotics target folate synthesis

A

Sulfonamides, Trimethoprim

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18
Q

Antibiotics target DNA gyrase

A

QuinolonesA

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19
Q

Antibiotic target RNA polymerase

A

Rifampicin

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20
Q

Antibiotics targeting protein synthesis

A

Tetracylines, Aminoglycosides, Macrolides, Clindamycin, Linezolid, Chloramphenicol

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21
Q

Antibiotics targeting 30s subunit ribosome

A

Tetracylines, aminoglycosides

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22
Q

Antibiotics targeting 50s subunit ribosome

A

Macrolides, Clindamycin, Linezolid, Chloramphenicol

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23
Q

Antibiotics that depend on CMax

A

Aminoglycosides, fluoroquinolones

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24
Q

Antibiotics that depend on AUC/MIC

A

Vancomycin, Azithromycin, Fluoroquinolones, Aminoglycosides, LinezolidA

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25
Antibiotics that depend on T >MIC (dosing interval)
Beta lactams, Clindamycin, Vancomycin, Macrolides
26
Antibiotics with >90% bioavailability
Clindamycin, Doxycycline, Linezolid, Metronidazole, Rifampin, Fluconazole, Voriconazole
27
Antibiotics with 80- 90% bioavailability
Amoxicillin, Cephalexin, Ciprofloxacin, Cotrimoxazole
28
Antibiotics with 60 - 80% bioavailability
Penicillin VK, Valganciclovir
29
Antibiotics with <60% bioavailability
Cefuroxime, Augmentin, Azithromycin, Aciclovir, Fosfomycin, Clarithromycin
30
Antibiotics with low oral bioavailability due to low intestinal permeability
Amikacin, Gentamicin, Ceftazadime, Vancomycin
31
Beta lactam antibiotic side effects
Hypersensitivity, neurotoxicity and reduced seizure threshold at higher doses, GI upset, LFT derangement
32
Glycopeptide side effects (Vancomycin)
Red Man Syndrome (fast infusion rate), nephrotoxicity
33
Aminoglycoside side effects
Ototoxicity, nephrotoxicity
34
Macrolide side effects
QTc prolongation, CYP3A4 enzyme inhibition
35
Fluoroquinolone side effects e.g. Ciprofloxacin
Tendinopathy, neurotoxicity and seizure threshold, QTC prolongation
36
Tetracycline side effects
Enamel staining, oesophageal irritation, photosensitivity
37
Antifolate (Cotrim)
Rash (including SJS), Cytopenia
38
Chloramphenicol side effect
Grey baby syndrme, aplastic anaemia
39
Clindamycin s/e
GI upset, rash
40
Metronidazole s/e
Peripheral neuropathy
41
Nitrofurantoin s/e
Peripheral neuropathy, hepatotoxic (long term), pulmonary fibrosis (long term), haemolytic anaemia in neonates
42
Daptomycin s/e
Myopathy, Rhabdomyolysis, Eosinophillic Pneumonia
43
Antbiotics that disrupt bacterial cell membrane
Daptomycin, Polymixin B
44
Penicillin mechanism of action
Bind to PBPs and inhibit completion of peptidoglycans and bacteral cell wall lysis
45
Penicillinase resistant penicillins
Methicillin, Flucloxacillin (treat staph + strep, **don't treat enterococci**)
46
Aminopenicillins
Amoxicillin (has amino group that give it some gram negative cover)
47
Natural penicillins
Penicillin G (Strep, Enterococci, Listeria, Neisseria, Syphillis)
48
Acyl Ureidopenicillins
Piperacillin (extended gram negative cover, including Pseudomonas)
49
Beta lactam/Beta lactamase inhibitor antibiotics (overcome acquired resistance mechanism of enzymatic modification)
Augmentin (Amox/Clavulanic Acid) and Tazocin (Piperacillin/Tazobactam)
50
Benefit of beta-lactam/beta lactamase inhibitor antibiotics
Better activity against gram negative bacilli, MSSA, Beta-lactam producing anaerobes. Tazoscin is also antipseudomonal
51
Cephalosporins mechanism of action
Same as penicillins (bind to PBPs, but differing affinity) and cause cell wall lysis. NO activity against enterococci and reduced activity against listeria. Resistant to beta lactamases produced by Staph Aureus
52
1st generation Cephalosporins
Cephazolin, Cephalexin (MSSA, Strep cover)
53
2nd generation Cephalosporins
Cefuroxime, Cefaclor (better Gram negative, specifically against H. Influenzae)
54
3rd generation Cephalosporins
Ceftriaxone, Cefotaxime, Ceftazadime (good gram negative and broad spectrum gram positive), good CNS penetration
55
What bacteria enzymes inactivate 3rd generation cephalosporins
ESBL and AmpC
56
Why can Ceftriaxone be once daily dosed?
Highly protein bound
57
Which 3rd generation cephalosporin has anti-pseudomonal activity?
Ceftazadime
58
4th generation cephalosporins
Cefepime, Ceftaroline
59
Cefepime coverage
Antipseudomonal, AmpC resistant
60
Ceftaroline coverage
Anti MRSA and resistant pnuemonocci, able to bind to PBP2a
61
Carbapenem antibiotics
Meropenem, Ertapenem, Imipenem
62
Carbapenem coverage
Gram positive, Gram negative including ESBL+, Pseudomonas (except Ertapenem). **Not MRSA or VRE**i
63
Side effect of Carbapenem
Neurotoxicity, lowers seizure threshold (especially Imipenem)
64
Types of antibiotic resistance
Intrinsic, Acquired and Adaptive/Inducible
65
Example of intrinsic antibiotic resistance
Vancomycin and Penicillins don't work for Gram negatives as cannot penetrate LPS layer, Cephalosporins don't work for Enterococci due to low affinity for enterococcal PBP
66
Example of acquired antibiotic resistance
Usually chromosome or plasmid mediated (MRSA = Chromosome, ESBL = Plasmid)
67
Example of adaptive/inducible resistance
Upregulates in presence of stressors e.g. ESCAPM versus beta lactams, Pseudomonas efflux pumps or porin channels versus everything
68
Four main mechanisms of antibiotic resistance
Enzymatic inactivation of antibiotic e.g. beta-lactamase Alteration of antimicrobial binding side Active efflux Alterations in membrane permeability
69
Choice of antibiotic for enterococcus faecalis
Penicillin or Amoxicillin
70
Choice of antibiotic for Enterococcus faecium
Vancomycin
71
Streptococcus Pneumoniae resistance mechanism
Decreased affinity of PBP. Enzyme gene alteration, leading to decreased affinity of penicillin to penicillin binding proteins (2b alterations give low level resistance, 2x alterations give high level resistance)
72
Streptococcus Pneumoniae choice of antibiotic
Penicillin (provided not meningitis), aiming MIC ) of 0.06 to 2 Cephalosporin (Ceftriaxone, Cefotaxime) if meningitis for CNS penetration, wouldn't rationalise to Penicillin unless MIC <0.06. Vancomycin added as potential for altered PBPs within pneumococcus
73
Strep Pneumoniae treatment if resistant to cephalosporins and penicillins
Vancomycin, add Rifampicin. Consider Linezolid or Moxifloxacin
74
Haemophillus Influenzae mechanism of antibiotic resistance
Enzymatic deactivation (beta-lactamase positive e.g. Amox resistant and Augmentin susceptible) Alteration of PBP (BLNAR- beta lactamase negative antibiotic resistance, treat with Cephalosporin or Cotrimoxazole)
75
Staphyloccous Aureus resistance mechanisms
90% produce enzyme (beta-lactamase/penicillinase) that inactivates penicillins
76
How do anti-staph penicillins work
Different side chain which reduces access of b-lactamase enzyme
77
Flucloxacillin adverse effects
Allergy, Bone marrow suppression at thigh doses, hepatotoxicity (including cholestatic liver failure), interstitial nephritis
78
What disease states is Vancomycin best for and why?
Hydrophillic drug therefore good for bacteraemia and endocarditis but poor tissue penetration
79
MRSA mechanisms of antibiotic resistance
Altered receptor binding or replacement of target site. Altered PBP2a (acquired genetic element unlike intrinsic set PBP1-4), which is encoded by the mec gene therefore penicillin can't bind. Lab can test for mecA gene by PCR s rapid MRSA diagnostics
80
Antibiotics which MRSA is resistant to
All penicillins and cephalosporins
81
MRSA therapy options
Clindamycin, Vancomycin, Cotrimoxazole, Erythromycin Doxycline, (Gentamicin, Rifampicin, Fusidic Acid). Linezolid, Daptomycin, Ceftaroline
82
What is the D zone test?
Inducible macrolide-lacosamide resistance. Modification of target RRNA of Staph Aureus on ERM gene. Erythromycin are strongest inducers of these gene but lincosamides are also weak inducers. Therefore if S.Aureus resistance to erythromycin on this test, there is a risk of inducible clindamycin resistance
83
What type of infection should Co-trimoxazole not be used for?
Endovascular
84
What does Co-trimoxazole cover?
MRSA, Gram positives and negatives, unusual infections (PJP, Toxoplasma, Stenotrophomonas)
85
Linezolid class of antibiotic
Oxazolidinone
86
Linezolid coverage
Gram positive action including MRSA and penicillin resistant S. Pnuemoniae, For serious VRE and MRSA organisms
87
Linezolid mechanism of action
Targets protein synthesis at early stage (?alternative to Clindamycin for STSS)
88
Side effects of Linezolid
Optic neuritis and peripheral neuropathy with >4 weeks therapy, thrombocytopenia
89
Anti-toxin production options in STSS
Clindamycin, Linezolid, IVIg
90
Gram negative organism mechanisms of resistance
ESBLs and AMPc
91
What antibiotic are ESBL organisms sensitive and resistant to?
Sensitive: Carbapenems +/- Amikacin. Nitrofurantoin for lower UTI, Fosfomycin Resistant: Penicillins, Cephalosporins, Monobactam
92
Risk factors for ESBL organism
Travel, prolonged hospitalisation, multiple courses of antibiotics, indwelling catheters, malignancy, GI tract disease
93
What organisms are ESBL found on
E. Coli, Klebsiella Pneumoniae, Klebsiella Oxytoca
94
What is AMPc
Cephalosporinase, inducible resistance to penicillins, cephalosporins and gram negative acting penicillins (Tazoscin)
95
What organisms produced AMPc
ESCAPM organisms. Enterobacter species, Citrobacter freundii, Serratia Marcescens, Proteus species, Providencia species, Morganella morganii
96
Oral antibiotics are non-inferior in
BJI without bacteremia, pneumonia, SSTI
97
MERINO trial finding
Tazoscin is not as effective as Meropenem for treatment of ESBL gram negative organisms

Infectious Diseases (9 decks)

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