Week 1: Cell wall active antibiotics Flashcards

Question

Cephalosporins half-life

Answer 1

t1/2 ~ 0.6-3 hours

Answer 2

Pen G 50% of TBW

Answer 3

* Primarily renal but also hepatic, so may require dose adjustment in liver or renal dysfinction * Organic acids are eliminated by renal tubular secretion * Secondary hepatic lysis of β-lactam ring * Pharmacokinetics altered in severe infection/disease * Cilastatin, decreases renal metabolism of the carbapenem imipenem, used to treat t_1/2 and decreased renal toxicity

Answer 4

* Allergic reaction * Bone marrow suppression * Nephrotoxicity * Hepatotoxicity

Answer 5

* Range from mild rash to anaphylaxis * Penicillin reaction to β-lactam, cephalosporin reaction to side chains so sometimes can tolerate different side chains

Answer 6

* Neutropenia \> thrombocytopenia * anemia

Answer 7

* interstitial nephritis \> Acute tubular necrosis

Answer 8

Cholestatic jaundice \> hepatitis

Answer 9

* Cefazolin (IV) * Cephalexin (po)

Answer 10

* Cefoxitin (IV) * Cefotetan (IV) * Cefuroxime (po)

Answer 11

Ceftriaxone (IV, IM)

Answer 12

Ceftaroline

Answer 13

* Vancomycin * Daptomycin * Colistin

Answer 14

* Ampicillin * Cephalexin

Answer 15

* Amoxicillin * Cephalexin

Answer 16

* Amoxicillin * Ampicillin

Answer 17

* cefoxitin * Ceftriaxone * cefotaxime

Answer 18

* Penicillin * Cefuroxime

Answer 19

* Cefuroxime * Cefotaxime * cefepime * ceftazidime

Answer 20

* Cefuroxime * Ceftriaxone * Ceftazidime

Answer 21

* Ceftriaxone

Answer 22

* Ceftriaxone * Cefotaxime

Answer 23

enzymes produced by bacteria that degrade β-lactam antibiotics as a mechanism of bacterial resistance

Answer 24

Penicillinase by S. aureus: breaks down penicillin

Answer 25

Carbapenamase by Klebsiella pneumoniae (AKA KPC) Klebsiella pneumoniae Carbapenamase

Answer 26

Metallo-β-lactamases, eg (New Delhi-1 (NMD-1))

Answer 27

* β-lactamases * Reduced entry * Increased efflux * Altered penicillin binding protein (Transpeptidase; PBP) * Acquisition of novel PBPs via plasmid

Answer 28

* Penicillin G * Penicillin V

Answer 29

Active against many GPC, less GNR, oral anerobes that do not make Penicillinase Examples: * Strep pyogenes * Strep agalactiae * Strep viridans * Clostridium perfringens * Listeria monocytogenes * Treponema pallidum

Answer 30

Depot preparation for single IM injection for long-term therapy with penicillin

Answer 31

Low-solubility results in prolonged low but therapeutic levels of PCN for susceptible infections (eg syphilis) * Procaine penicillin G is detectable in blood 24 hours * Benzathine penicillin G at low levels for 2-3 weeks

Answer 32

Contains equal amounts of benzathine and procaine salts of PCN for deep IM injection

Answer 33

* Narrow-spectrum, penicillinase-resistant * MSSA (Methicillin-sensitive Staph aureus) * also covers what penicillin covers * S. aureus is tested for oxacillin susceptibility, call it methicillin-sensitive, treat with naficillin

Answer 34

S. aureus that carries mecA gene which encodes a resistant PBP

Answer 35

1/3 of S. aureus isolates at UNMH are resistant to methicillin

Answer 36

* Ampicillin (IV) * Amoxicillin (po)

Answer 37

broad-spectrum, penicillinase-resistant * GPC, aerobic GNR, some anaerobes * Strep pyogenes * Strep viridans * Enterococcus * E. coli * H. influenza

Answer 38

β-lactamase inhibitors

Answer 39

Covalent-inhibitors of penicillinase with no Penicillin activity

Answer 40

* Clavulanate * Sulbactam * tazobactam * avibactam

Answer 41

Large molecules that do not cross the blood-brain barrier

Answer 42

* Amoxicillin/Clavulanate (Augmentin) po * Ampicillin/Sulbactam (Unasyn) IV * Piperacillin/Tazoactam (Zosyn) IV

Answer 43

β-lactamase inhibitors broadens the spectrum of ampicillin (ie Staph aureus, β-lactamase producing H. influenzae)

Answer 44

Piperacillin/Tazobactam

Answer 45

* Ampicillin + additional GNR (Pseudomonas) and Anaerobes (Baceroides fragilis) * addition of β-lactamase inhibitor adds: Staphylococcus, GNRs with β-lactamase production and Anaerobes

Answer 46

addition of β-lactamase inhibitor adds: Staphylococcus, GNRs with β-lactamase production and Anaerobes

Answer 47

Cephalosporins are classified in generations based on sequence of development and specturm of activity

Answer 48

* Start with excellent GPC coverage, with the exception of Enterococci (intrinsically resistant to cephalosporins) * With subsequent generations there is increasing effectiveness against GNRs

Answer 49

Some cross-reactivity with PCNs so can be allergic to both

Answer 50

Cefazolin (IV) Cephalexin (po)

Answer 51

* GPC * Some aerobic GNR * Examples: Group A Strep, Group B Strep, Methicillin-sensitive Staph aureus, E. coli, K. pneumonia

Answer 52

* Enterococci * Listeria * Anaerobes

Answer 53

Does not cross BBB

Answer 54

* Cefotetan (IV) * Cefoxitin (IV) * Cefuroxime (po)

Answer 55

* Covers more GNR and some aerobes * Not as active as 1st gen cephalosporins against GPCs * More penicillinase resistant * examples * E. coli * K. pneu * Proteus * Haemophilis influenza * Moraxella catarrhalis * B. frag (cefoxitin)

Answer 56

* Ceftriaxone (IV)

Answer 57

* GPCs * Enterobacteriacea * Neisseria

Answer 58

Good CNS penetration (requires more frequent dosing; q12 hours)

Answer 59

* Cefepime (IV)

Answer 60

* Adds coverage against Pseudomonas

Answer 61

Ceftaroline (IV)

Answer 62

Adds coverage against MRSA (Is the ONLY β-Lactam with activity against MRSA)

Answer 63

Ceftaroline is the ONLY β-Lactam with activity against MRSA

Answer 64

* Broad spectrum against GPCs, GNRs (including Pseudomonas), anaerobes * Typically reserved for resistant infections * Is penicillinase resistant however, their is emergence of Carbapenem Resistent Enterobacteriaceae

Answer 65

Imipenem is combined with cilstatin to prevent rapid renal degradation to renal toxic metabolites

Answer 66

no coverage against Enterococcus or Pseudomonas

Answer 67

Not cross-reactive with β-lactams so useful when allergic to PCN if Gram-negative infection

Answer 68

* Actvity against aerobic GNR ONLY * Enterobacteriacea (eg E. coli) and Pseudomonas * Penicillinase resistent * Activity against NMD1 * Not cross-reactive with β-lactams so useful when allergic to PCN if Gram-negative infection

Answer 69

Glycopeptide

Answer 70

Glycopeptide binding to D-ala end of the GP cell-wall building block, preventing cross-linking by transglycolases Unable to penetrate GNs

Answer 71

* Associated with substituition of another amino acid (D-lactate or D-serine) for the Vancomycin binding site (Terminal D-ala) * Increase in cell wall thickness of Staph aureus will increase MIC of Vancomycin without conferring true resistance

Answer 72

* IV * Oral not absorbed so only used for treating GI lumen infection with C. diff * t_1/2 ~ 6 hours * eliminated by glomerular filtration

Answer 73

t_1/2 ~ 8-9 hours

Answer 74

Vancomycin is eliminated by glomerular filtration

Answer 75

IV because oral is not absorbed so it is only useful for treating GI lumen infections with C. diff by oral route

Answer 76

t_1/2 ~ 6 hours

Answer 77

* Requires loading dose to reach steady state fast * Therapeutic monitoring of (Steady-state) serum trough concentration after the 3rd or 4th dose

Answer 78

Area under curve:Minimum inhibitory concentration

Answer 79

AUC₂₄:MIC \>400 correlates with treatment success in Staph aureus

Answer 80

* S. aureus (including MRSA) * S. epidermidis * Streptococcus spp. * Enterococci spp. * Corynebacterium * Clostridium

Answer 81

* Nephrotoxicity * Concern about nephrotoxic effect of combiniation Pip/Tazo and vancomycin * Histamine release (flushing or Red Man Syndrome) \*NOT a true allergy\* \*this is historically related with fast infusions

Answer 82

Is historically related with fast infusions of Vancomycin

Answer 83

Lipopeptide

Answer 84

Binds to bacterial cell-membrane causing depolarization and loss of membrane potential; bactericidal

Answer 85

GPC only includes MRSA (Methicillin-resistent Staph aureus) VRE (Vancomycin-Resistent Enterococci)

Answer 86

* Dosed IV q24 hours

Answer 87

Renal elimination

Answer 88

Does not get into CNS

Answer 89

Surfactant in lungs inactivates drug

Answer 90

Concentration dependent killing with Post-antibiotic effect

Answer 91

* Rhabdomyolysis (monitor CPK level weekly) * eosinophilic pnemonia

Answer 92

Polymyxin antibiotic

Answer 93

Acts as a detergent to rapidly solubilize membranes in GN bacteria \*Concentration depedent\*

Answer 94

* GN only * Used in salvage therapy for milti-drug resistent Pseudomonas, Acinetobacter (monotherapy avoided)

Answer 95

* Cationic drug with nephrotoxicity and neurotoxicity (cf aminoglycosides, cis-platinol) * Nephrotoxic, vertigo, slurred speech * Interferes with neuromuscular junction: Muscle weakness, apnea, paresthesias

Answer 96

Probenecid (gout drug, also inhibits renal secretion of penicillins) thus allowing for greater concentrations in the body

Answer 97

get their name because they are similar to the penicillins found in nature * Penicillin G (IM and/or IV) * Penecillin VK (oral) * Probenecid (gout drug but also inhibits renal secretion of PCNs)

Answer 98

* modified Penicillin binding proteins (mutations) S. pneumonia * Reduced bacterial cell penetration (gram neg, also bacteria with porins which can be downregulated) * Beta-lactamase enzymes

Answer 99

* Staphylococcus aureus * Haemophilus influenzae * Gram-negative rods * Moraxella catarrhalis * Neisseria gonorrhoeae * Legionella pneumophila * Anaerobic Gram-negative bacilli (Bacteroides, Prevotella, and Porphyromonas spp.) * Fusobacterium spp.

Answer 100

Penicillinase

Answer 101

* Clavulanic acid * Sulbactam * Tazobactam

Answer 102

* strep pyogenes (strep throat) * Actinomyces (gram positive anaerobe in mouth * treatment of choice for Treponema pallidum (syphilis) * Rarely (only in susceptible isolates) - Neisseria meningitides, Strep pneumonia

Answer 103

* C. diff infection (diarrhea) -\> pseudomembraneous colitis * Jarisch-Herxheimer reaction * Type I IgE hypersensitivityanaphylaxis * Type II hemolytic anemia from IgG antibodies bind to PCN which are bound to RBCs (hapten) (Coombs test: positive) * Type III immune complex serum sickness IgG fever urticaria arthritis * Type IV T-cell-mediated delayed maculopapular rash (more common with people that have a viral infection) (EBV pharyngitis) * Steven-Johnson syndrome * Type IV T-cell-mediated - Interstitial nephritis (PCN acts as hapten causing immune response in kidneys)

Answer 104

* Sulfonamides * Aminopenicillins * Cephalosporins

Answer 105

* fever * oliguria * increased BUN/Cr * Eosinophils in urine * white cells and WBC casts (sterile pyuria)

Answer 106

The Coombs' test is used to detect antibodies that act against the surface of your red blood cells. The presence of these antibodies indicates a condition known as hemolytic anemia, in which your blood does not contain enough red blood cells because they are destroyed prematurely.

Answer 107

* urticaria * fever * arthritis * lymphadenopathy

Answer 108

occurs usually 2 hours after PCN therapy for spirochete infections (classically in syphilis) * fever * chills * flushing * hyperventilation Mimics hypersensitivity reaction but is the result of bacteria dying off and causing an acute immune response

Answer 109

* Prototype was Methicillin (no longer used because high incidence of adverse effects particularly interstitial nephritis) * Oxacillin * Nafcillin * Dicloxacillin

Answer 110

The side-chain protects the beta-lactam ring from staph penicillinase

Answer 111

Covers basic PCNs and also non-MRSA S. aureus and most Strep

Answer 112

* Amoxicillin (oral) * Ampicillin (IV)

Answer 113

they have an amino group attached allows them to penetrate porin-channel of GNeg bacteria They are however, still sensitive to beta-lactamases

Answer 114

penicillin bacteria and some gram negatives

Answer 115

* community acquired cellulitis * Impetigo * Staph endocarditis based on culture data

Answer 116

same as PCNs

Answer 117

* H. influenza * E. coli * Proteus * Salmonella * Shigella * Listeria (gram +) *

Answer 118

* Otitis media * Bacterial sinusitis * Meningitis * newborns and elderly * Listeria coverage

Answer 119

Same as PCNs * Type IV delayed maculopapular rash is most likely with Aminopenicillins * Steven-Johnson syndrome also

Answer 120

* amoxicillin/Clavulonic Acid (augmentin) * Ampcillin/Sulbactam (Unasyn)

Answer 121

increases activity against S. aureus and H. flu and also against anaerobes (B. fragilis)

Answer 122

* Otitis media/sinusitis (Broad-spectrum) * Bite wounds (polymicrobial with anaerobes

Answer 123

* Ticarcillin * Piperacillin

Answer 124

they have greater porin channel penetration

Answer 125

Same as PCN but effective against more Gneg than aminopenicllins and also effective against Pseudomonas aeruginosa

Answer 126

Ticarcillin

Answer 127

* Ticarcillin/Clavulanate (Timentin) * Piperacillin/tazobactam (Zosyn)

Answer 128

* Most Gpos (NOT MRSA!) * More Gneg (including Pseudomonas) * Most anaerobic bacteria

Answer 129

Usually reserved for very sick patients such as * Sepsis * Pneumonia

Answer 130

* Penicillins * Carbapenems * Aztreonam * Cephalosporins

Answer 131

Beta-lactam antibiotics Older carbapenems * Imipenem and Meropenem Newer carbapenems * Ertapenem * Doripenem

Answer 132

same as for penicillin they bind the Pencillin binding protein or peptiidoglycan transpeptidase and prevent it from cross-linking the peptidoglycan cell wall resulting in bacterial autolysis Thus all beta lactams are bactericidal They are all POTENTIALLY susceptible to beta-lactamases

Answer 133

they are not penicillins but are beta-lactams and they are resistant to cleavage from most beta-lactamases

Answer 134

Extended spectrum beta-lactamase plasmid-mediated bacterial enzymes that confer resistance to most beta-lactam antibiotics (penicillins, cephalosporins and aztreonam)

Answer 135

Found only in some Gneg bacteria such as * E. coli * Klebsiella * Pseudomonas * Enterobacter * Salmonella * Serratia * Shigella

Answer 136

The drug of choice for ESBL bacteria! * Gram (+) * Gram (-) including pseudomonas, enterobacter * anaerobes including B. fragilis

Answer 137

imipenem unique problem in that it was metabolized in the kidneys by dehydropeptidase 1 and therefore lost antibacterial effect as well as gave off nephrotoxic metabolites So imipenem was given with Cilastatin (dehydropeptidase 1 inhibitor) to prevent this

Answer 138

once daily dosing but it has some resistance in ESBL bacteria and also weak activity against pseudomonas

Answer 139

* Common side effects * NVD * Skin rash * Neurotoxicity * Seizures * inhibition of GABA receptors * especially at high doses or with renal failure * reduced risk with Meropenem

Answer 140

Aztreonam (the Beta-lactam ring is not fused to another ring)

Answer 141

binds to pencillin binding protein 3 (PBP-3) which is found in Gneg bacteria and prevents cross-linking of peptidoglycan and thus is bactericidal Has limited susceptibility to Beta-lactamase (has some resistance in ESBL bacteria)

Answer 142

* only active against Gneg bacteria * Doesn't bind PBP of Gpos bacteria thus has no activity against Gpos or anaerobes * Is active against Pseudomonas

Answer 143

usually reserved for hospitalized patients synergystic with aminoglycosides Does **NOT** have cross-reactivity for patients allergic to penicillins \*\*\*\*\*Key niche: PCN allergy\*\*\*\*

Answer 144

beta-lactam antibiotics that are divided into 4 generations starting out covering Gpos but with each generation progressively covering more Gneg

Answer 145

* Cefazolin * Cephalexin

Answer 146

* Cefuroxime * Cefoxitin * Cefotetan

Answer 147

* Ceftriaxone * Cefotaxime * Ceftazidime

Answer 148

* They were developed to treat S. aureus resistant to penicillin * covers many Gpos bacteria including S. aureus (**NOT** MRSA) * stable against S. aureus' beta-lactamases * Does **NOT** cover Enterococcus or Listeria * **Remains** susceptible to Gneg beta-lactamases

Answer 149

* Surgical wound (skin) infections * Cefazolin is given pre-op for prevention

Answer 150

designed to treat amoxicillin resistent-infections

Answer 151

* increased affinity for Gneg PBPs * H. influenzae, Enterobacter, Proteus * E. coli, Klebsiella, Serratia, N. gonorrhea * More resistant to beta-lactamase * Increased anaerobic coverage * B. fragilis

Answer 152

* Cefuroxime (oral) * Otitis media (S. penumonia, H. flu) * UTI in children (E. coli, no fluoroquinolones) * Cefoxitin/Cefotetan (IV) * PID (covers Neisseria, also give doxycycline for Chlamydia) * Pre-op in children with appendicitis * E. coli * covers Gnegs and some anaerobes * usually given with metronidazole

Answer 153

* broad Gneg coverage * more Gneg PBP affinity * even greater resistance to beta-lactamases * Ceftriaxone, Cefotaxime: poor coverage of pseudomonas * Ceftazidime: covers Pseudomonas * Most achieve good CSF penetration (meningitis)

Answer 154

* Ceftriaxone, Cefotaxime: poor coverage of pseudomonas * \*\*\*Ceftazidime: covers Pseudomonas\*\*\*\*

Answer 155

**Ceftazidime:** * covers pseudomonas * typically reserved for hospitalized patients with Gneg infections * Sepsis/Pneumonia **Ceftriaxone** * good CSF penetration so used often for meningitis * active against S. pneumoniae, N. meningitidis * Commonly used for N. gonorrhea

Answer 156

* good CSF penetration so used often for meningitis * active against S. pneumoniae, N. meningitidis * Commonly used for N. gonorrhea

Answer 157

Cefepime: Broad spectrum

Answer 158

Broad spectrum * MSSA * Many Gpos * Many Gneg (including Pseudomonas) * Resistent to some ESBL

Answer 159

Hospitalized patients with Gneg infections

Answer 160

**Most** Penicillins (**NOT** antistaph PCNs) 1st gen cephalosporins 2nd gen cephalosporins 3rd gen cephalosporins 4th gen cephalosporins Aztreonam Carbapenems (ESBL drug of choice) **Least**

Answer 161

Ceftaroline

Answer 162

* **\*\*\*Active** against MRSA\*\*\* * Binds PBP2a (MRSA specific PBP) * Covers MRSA and VRSA * Some Gnegs (**NOT** Pseudomonas) * Studied in skin infections and pneumonia

Answer 163

* modify PBPs * Altered cell permeability * beta-lactamase

Answer 164

Hypoprothrombinemia - associated with N-methylthiotetrazole (NMTT) side chains (Cefotetan, Cefozolin) which inhibits epoxide reductase (similarly to warfarin) decreasing hepatic synthesis of clotting factors, prolong the PT/INR (reversible with Vitamin K (common in malnourished pts) * Vitamin K deficiency (increased INR and potential bleeding from the killing of bacteria which generate Vitamin K2 in the gut) \*problem for patients on warfarin (can be caused by any antibiotic) * increased risk of Nephrotoxicity w/ aminoglycosides * Disulfiram reaction Basically same as penicillins * Type I anaphylaxis * Type II hemolytic anemia * Type III serum sickness * Type IV interstitial nephritis * Type IV Steven Johnson syndrome/TEN * Also shares some cross-reactivity with penicillins traditionally cited as 10% but may be lower

Answer 165

* alcohol consumption with cephalosporins or disulfiram * warmth, flushing, sweating * from inhibition of acetaldehyde dehydrogenase leading to accumulation of acetaldehyde * occurs with some certain side chains such as (Cefoperazone, Cefamandole, Cefotetan)