Cell Wall Inhibtors and Abx Resistance Flashcards

Question

Methicillin

Answer 1

* First β-lactamase stable penicillin * Now 46% of S. aureus resistant * Use oxacillin or nafcillin * Often cross-resistant to non-β-lactams ⇒ "multiple-resistant S. aureus" * Use vancomycin

Answer 2

* **Acquisition of mecA gene encoding PBP2a** * Transpeptidase with very low β-lactam affinity * Cross resistant to non-β-lactam abx * Expression in bacterial populations may be low ⇒ **heterogeneous resistance** * Detect w/ PCR for mecA gene or agglutination test for PBP2a * β**-lactamase overproduction** * **Modification of existing PBPs**

Answer 3

Vancomycin binds d-Ala-d-Ala. * **High level resistance** * **Substitute D-lactate for terminal D-Ala** * Incorporation into peptidoglycan can still occur * Vancomycin cannot bind and inhibit * VanA, VanB, VanD strains * **Low level resistance** * **Substitute D-Ser for D-Ala** * VanC, VanE, VanG strains * Resistance currently limited to Enterococci * May eventually transfer to Staph

Answer 4

* **Chromosomal** * Point mutations * Low frequency * **Plasmid** * Same or related species * Low freq. by transformation * High freq. by conjugation * **Phage** * Most common * Lytic phage ⇒ generalized transduction * Lysogenic phage ⇒ specialized transduction * **Transposon** * Abx resistance genes flanked by two IS

Answer 5

* **Transformation** * Free DNA * Ex. Strep pneumoniae ⇒ chromosomal beta-lactamase genes * **Transduction** * Lytic phages * Ex. S. aureus ⇒ acquired beta-lactamase gene * **Conjugation** * Plasmids * Machinery encoded by Tra genes * Ex. Enterobacteria & other gram neg ⇒ most common method of transferring multidrug resistance

Answer 6

* ⊗ Batoprenol * Prevents transport of cell wall monomers out of the cell * Only used topically * Treat minor skin and eye infections caused by Staph and Strep

Answer 7

* **Vancomycin** and **Dalbavancin** * Time-dependent * Poor bioavailability * Spectrum * Gram pos. aerobe and anaerobes including MRSA * Does NOT kill beta-lactam susceptible Staph as fast as beta-lactams

Answer 8

* **Binds a-alanyl-d-alanine ⇒ ⊗ cell wall synthesis** * Covers many gram pos. resistant to other abx * MRSA * MSSA * Strep * Some enterococci resistant ⇒ **VRE** * PO only for C. diff * IV can cause flushing ⇒ **"red man syndrome"** * Slow infusion rate and give antihistamines * Associated with **nephrotoxicity and ototoxicity** * Inc. renal damage possible with concurrent nephrotoxins

Answer 9

* Enzymes located on the cytoplasmic membrane * Responsible for cell wall synthesis * Some have transpeptidase activity * Inhibited by beta-lactam abx

Answer 10

* All contain a beta-lactam ring * Opens up and binds PBPs * Substitutions alter pharmacologic profile

Answer 11

* Most are **time-dependent** * **Most eliminated via renal tubular secretion** * Except nafcillin, aztreonam, and some cephalosporins * **PCN widely distrubted to most tissues except CNS** * Will cross BBB is meninges inflamed * Can be used to treat meningitis

Answer 12

* Used to treat gout * Inhibits tubular secretion * **Prolongs half-life of renally excreted beta-lactams**

Answer 13

* Penicillioic acid combines with host proteins to form Ag * Results in hypersensitivity reactions

Answer 14

* Patient reported drug allergies unreliable * True PCN allergies in 7-23% of pts reporting hx of allergy * PCN allergy can be confirmed through skin test * **Desensitization protocol** when PCN needed in pt with an allergy * **Cephalosporins** * Lower incidence of hypersensitivity than PCN * **5% cross-reactivity w/ PCN allergies** * **Carbapenems** * **1% cross-reactivity w/ PCN allergies** * **Aztreonam** * **No cross-reactivity w/ PCN allergies**

Answer 15

* Hypersensitivity reactions * _Ampicillin_ * Likely to cause **skin rash in pts w/ certain viral infections** like monomucleosis * _PCN @ high doses_ * **Seizures** * Disrupt gut flora ⇒ **diarrhea and superinfections like C. diff** * Esp. 3rd/4th gen. cephalosporins, fluoroquinolones, carbapenems, clindamycin

Answer 16

* **Inactivation of abx by beta-lactamase** * Chromosomal and plasmid expression * Constitutive or inducible expression * Ex. Staph to Penicillin G * **Reduced affinity of PBP for abx** * Ex. Staph to methicillin * **Decreased entry of the drug into bacteria through outer membrane porins** * Ex. Gram neg. to various beta-lactams

Answer 17

"Natural Penicillins" * Meds: * **Penicillin G** ⇒ IV * **Pencillin V** ⇒ PO * Procaine and benzathine penicillin ⇒ long acting depot * 30 min half-life ⇒ frequent doses * Most bacteria are resistant * Useful spectrum: * **Strep** * **Enterococci** * **Treponema pallidum** * Main uses: * Susceptible strep infections * Syphilis

Answer 18

"Antistaphylococcal" * Meds: * **Nafcillin** * Hepatically eliminated * High incidence of phlebitis * **Oxacillin** * **Dicloxacillin** * Not routinely used d/t dosing issues * Spectrum: * **MSSA** * **Strep** * Uses: * **Suseptible staph infections** * Endocarditis, osteomyelitis, cellulitis * If staph resistant to one, resistant to all ⇒ MRSA * Kill staph faster than vancomycin, should be used if suseptible

Answer 19

"Extended-spectrum penicillins" * Drugs: * **Amoxicillin** ⇒ IV, PO * **Ampicillin** ⇒ PO * Spectrum: * Strep * Enterococci * Listeria * H. pylori * Some non-beta-lactamase producing GNR * Uses: * URI * UTI * PUD * Enterococcal infections * **Suseptible to beta-lactamases** * Amino group ⇒ **improved gram neg. activity** * **High incidence of diarrhea when given PO**

Answer 20

* IV or PO * Higher bioavailability than ampicillin * Uses: * Prophylaxis for endocarditis in susceptible pts * Susceptible enterococci

Answer 21

* Must be used w/ aminoglycoside for enterococci * Protein synthesis inhibitor * Used for serious infections * Endocarditis

Answer 22

* Aminopenicillins ⇒ intrinsic activity against GNR * Beta-lamtamase inhibitors ⇒ allow drug to exert effect * **Good for empiric therapy for hospital acquired infections** * Activity against aerobe and anaerobes * **Good for mixed infections** * Intra-abdominal infections * Diabetic ulcers * Aspiration PNA

Answer 23

* Meds: * **Piperacillin ± tazobactam** * **Ticarcillin** * Useful spectrum ⇒ parent drug + most beta-lactamase producing bacteria * **Pseudomonas** * **Strep, MSSA, enterococci** * **Anaerobes** * b. fragilis and other gut bacteria * Better GNR coverage than parent drug along * **Active against pseudomonas and other drug-resistant GNR** * Common hospital acquired infection * Tazobactam ⇒ beta-lactamase inhibitor * Restores coverage for MSSA

Answer 24

* Classified by generation * More resistant to beta-lactamase than PCN * Most have poor activity against anaerobes

Answer 25

* Meds: * **Cefazolin** ⇒ IV * **Cephalexin** ⇒ PO * Renal elimination * **No CNS penetration** * Useful spectrum: * **MSSA** * **Strep** * **Some GNR** * Main uses: * **Surgical prophylaxis** * **Cellulitis**

Answer 26

* Meds: * **Cefaclor** * **Cefuroxime** * "Cephamycins" * **Cefoxitin** * **Cefotetan** * **Better gram neg. and slightly weaker gram pos. activity compared to 1st gen** * Most numerous, least commonly used * No CNS penetration * Main uses: * **URIs** * Surgical prophylaxis ⇒ cephamycins

Answer 27

**Active against many anaerobes in GI tract.** **Used for surgical prophylaxis in abdominal surgery.** * **Cefoxitin** * **Cefotetan** * N-methylthiotetrazole **(MTT) side chain** * **⊗ Vit K production** * Prolongs bleeding * **⊗ acetaldehyde dehydrogenase** * Causes flushing with ETOH ⇒ **disulfiram-like reaction**

Answer 28

**Broad spectrum agents** * Meds: * **Ceftriaxone** * **Cefotaxime** * **Cefpodoxime** * **Ceftazidime ± avibactam** * No gram pos. coverage * Covers pseudomonas * **Enters CNS** * Compared with 2nd gen * ↑ **Gram neg.** * **↑ Strep** * **↓ Staph** * Main uses * Meningitis * CAP/HAP * Lyme disease * Skin and soft tissue infections * UTI * Febrile neutropenia * Gonorrhea

Answer 29

* **Dual elimination ⇒ liver and renal** * No dose adj. for renal function * Uses: * Hospital aq. meningitis and HAP * Strep. pneumonae coverage * CAP * Strep. pneumonae most common * Lymes disease * Skin/soft tissue * Not great but convient qDay dose * UTI * **Gonorrhea** * **Ceftriaxone + Azithromycin for chlamydia**

Answer 30

**Has MMT Side Chain.** ⊗ Vit K production ⊗ acetaldehyde dehydrogenase ⇒ disulfiram-like reaction

Answer 31

* No gram + coverage * **Does cover pseudomonas** * Given with **avibactam** * Cephalosporin/beta-lactamase inhibitor combo * Combo active against many gram neg. bacteria * **Treat complicated intraadominal and urinary tract infections**

Answer 32

**Cefepime** * **Broadest spectrum cephalosporin** * **Gram neg** * **Gram pos** * **Pseudomonas** * **Not as good against anaerobes** * More rapid penetration * Able to bind multiple PBPs * Lower affinity for several beta-lactamases * **Given IV only** * **Enters CNS** * **Good for many hospital aq. infections** * Overkill for community-aq. infections

Answer 33

**Ceftaroline** * **Only cephalosporin with MRSA coverage** * Designed to bind PBP 2a of MRSA * Think of it like Ceftriaxone + MRSA * Spectrum: * **MRSA** * **MSSA** * **Strep** * **Enteric GNR** * No pseudomonas coverage * **Modest activity against Enterococcus faecalis** * None against Enterococcus faecium * Uses: * **Skin and soft tissue infections** * **CAP**

Answer 34

**Aztreonam** * **Used for gram neg. infections in pts w/ beta-lactam allergies** * **Including pseudomonas** * **Safe to give to pts w/ beta-lactam allergies** * Except if they are allergic to Ceftazidime * **Enters CNS** * Penetrates tissues well * Renally elimiated

Answer 35

**The most broad spectrum antibiotic.** * Meds: * **Imipenem/cilastin** * **Doripenem** * **Ertapenem** * **Meropenem** * **1% cross-reactivity w/ PCN allergies** * _All drugs have simiar spectrum except ertapenem_ * **MSSA, Strep, E. faecalis, anaerobes** * **Many GNR including Pseudomonas** * Drugs of choice for extended-spectrum beta-lactamase (ESBL) producing GNR * Including E. coli and Klebsiella pneumoniae * Main uses: * **Nosocomial infections** * **Mixed aerobic/anaerobic infections** * **Febrile neutropenia** * All given IV only * Renal elimination * **Higher incidence of seizures** * Causes nausea ⇒ rate-related

Answer 36

* NOT effective against Pseudomonas and Acinetobacter * Longest half-life ⇒ used for outpatient infusion therapy for susceptible infections

Answer 37

* **Highest incidence of seizures** * **Avoid in pts w/ meningitis** * More likely to enter CNS * Metabolized in the kidneys to nephrotoxic product * ALWAYS given with **Cilastin** * Blocks this reaction

Answer 38

* Meds: * Daptomycin * Colistin, Polymixin B * Cyclic lipopeptides * Inserts into cell membrane * Bactericidal

Answer 39

* Cyclic lipopeptide * **Concentration-dependent** * Poorly absorbed * Inactivated by surfactant ⇒ inactive in lungs * Excreted renally * Spectrum * **Gram pos. aerobes and anaerobes** * **Including MRSA and VRE** * Uses: * Bacteremia * Skin and soft tissue infections * Endocarditis * Adverse effects: * **Creatine kinase elevation** * **Myopathy** * **Rhabdomyolysis**

Answer 40

**Colistin (Polymixin E) & Polymyxin B** * MOA: Bind cell membrane of gram neg. distrupting permeability * Poor bioavilability * Colistin is excreted renally * Polymyxin B is not * Given by inhalation, IV, or topical * _Spectrum:_ * **Gram neg. organisms** * **MDR Pseudomonas** * **Acinetobacter** * **Klebsiella** * Inactive against Serratia, Providentia * _Uses:_ * **MDR GNR infections** * **Topical infections** * **Prophylaxis of PNA in colonized CF patients** * _Adverse effects:_ * **Nephrotoxicity** ⇒ common * **Neurotoxicity** ⇒ uncommon

Cell Wall Inhibtors and Abx Resistance Flashcards

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