Antibacterials 2 Flashcards by Gopu Premrajan

What are some disadvantages to combination therapy

Can select for multiple drug resistant bacteria

Agents that act only on multiplying bacteria should not be given with bacteriostatic drugs

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Mechanisms of synergism in combination therapy

sequential blockage: trimethoprim + sulfamethoxazole in which two steps in the same pathway are blocked
blockade of drug inactivating enzymes: clavulanic acid + amoxicillin; one drug that inhibits the β lactamase
enhanced drug uptake

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3 mechanisms by with bacteria have antibiotic resistance

altered uptake of antibiotic; ↓ in permeability and/or uptake mechanism; ↑ in multi drug resistance pumps
altered target; altered receptor affinity
drug inactivation; bacteria produce enzymes to inactivate the drug

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Primary resistance is _______

Innate

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Transfer of genetic information for acquisition of resistance genes in bacteria can occur via: (4)

Conjugation
Transposons
Transduction
Transformation

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Competent bacteria have the ability to _______

Uptake DNA from the environment (this process is called transformation)

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The process of transformation is facilitated by __________ and requires ______

Bacterial DNA binding proteins; Calcium

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Conjugation involves the transfer of information using _______

Plasmids which are circular DNA material that have restiance genes

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_______ is the donor and ______ is the recipient in conjugation and is only found in gram ___________ bacteria

F+; F-; negative

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What is the mechanism of transduction

Bacteriophage injects DNA into the host bacterial cell
- lytic phage infects bacterium in which ther is bacterial DNA cleavage and parts of the bacterial DNA gets packaged in the phage and are used to infect new bacterium

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Transposons are _______

Mobile genetic elements that can be trasnferred through plasmids

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Complications of antibiotic therapy

hypersensitivity
direct toxicity: ex. Amniglycosides causing ototoxicity
superinfection: a new or secondary infection that occurs during antimicrobial therapy of a primary infection

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Drugs that are cell wall synthesis inhibitors

β lactam antibiotics: penicillins, cephalosporins, carbapenems, monobactams 
Vancomycin
Daptomycin
Bacitracin
Fosfomycin

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What organisms are cell wall synthesis inhibitors ineffective against due to primary resistance?

Mycoplasma, Protozoa, fungi, viruses

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Use of cell wall synthesis inhibitor antibiotics requires ________

Actively proliferating bacterial because cell wall synthesis must be actively occurring

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What drugs are β lactamase inhibitors and what is their use

Clavulanic Acid, sulbactam, Tazobactam

They bind and inactive most β lactamases

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What is the target site of β lactam antibiotics?

Penicillin binding proteins specially transpeptidase which is a bacterial enzyme involved in the last step of cell wall synthesis

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Are beta lactams bactericidal or bacteristatic? Why?

Bactericidal; inhibits last step of peptidoglycan synthesis and this will activate auto lytic enzymes which initiate cell death

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Pencillin’s abilyt to reach the penicillin binding protein is determined by:

Size
Charge
Hydrophobicity

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Pencillins can easily cross the cells all of gram _________ organisms

Positive

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What synergistic combination of antibiotics is used for empirical treatment of infective endocarditis? Explain

Penicillin + aminoglycoside

Penicillin facilitates movement of aminoglycosides through the cell wall

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4 mechanisms of penicillin resistance

inactivation by β lactamases
modification of targe PBP (penicillin binding protein)
impaired penetration of drug to target PBP
increased efflux

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Example of altered target PBP

MRSA; low affinity for β lactam antibiotics

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What is penicillin G most commonly used for?

Syphilis
strep infections
susceptible pneumococci

Penicillin G is susceptible to β lactamases

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Applications of penicillin G Benzathine and how is it administered

Syphilis Rheumatic fever prophylaxis Given via IM (regular penicillin G is given via IV) This form of penicillin has a longer half life

Route of administration of penicillin V

Orally because it is more acid stable

What is penicillin V used to treat?

Pharyngitis, tonsillitis, and skin infections Mostly mild-moderate infections

What are the antistaphylooccal penicillins? (4) and are they β lactamase resistant?

- methicillin - nafcillin - oxacillin - dicloxacillin They are β lactamase resistant and inactive against MRSA

Extended spectrum pencillins: (2) and they are usually given with _____

Ampicillin, amoxicillin Β lactamase inhibitors

Amoxicillin is typically given with _______ and is the preferred prophylactics treatment for _________

Clavulanic acid; treatment for dog, cat and human bites Also given for: acute otitis media, strep pharyngitis, pneumonia, skin infections and upper respiratory infections, and UTI’s

Ampicillin is typically given with __________

Sulbactam

Antipseudomonal pencillins: (3) and when are they given

Carbenicillin, ticarcillin, piperacillin Often combined with β lactamase inhibitors Given to treat moderate to severe infections such as: uncomplicated and complicated skin, gynecological and intra-abdominal infections and febrile neutropenia

Penicillins achieve therapeutic levels in _____________ but not in __________

Pleural, pericardial, peritoneal, synovial fluids, and urine; Not in prostate and eye (cant be used to treat prostatits and uveitis)

Which antibiotic would you give a patient who has renal failure?

Nafcillin because that is the only one that is excreted in the bile The others are primarily excreted via the kidney so a patient with renal failure would not be able to excrete them

Adverse effects of pencillins

GI disturbances (diarrhea)

Adverse effect of ampicillin

Pseudomembranous colitis

Macuopapular rash is an adverse effect seen in ________ and ______

Ampicillin; amoxicillin

_______________ is an adverse effect in taking methicillin

Interstitial nephritis

An adverse effect of nafcillin is _______

Neutropenia

Cephalosporins are less/more susceptible to β lactamases than pencillins

Less

As you go from first to later generation cephalosporins, gram __________ activity diminishes while gram ___________ activity increases

Positive; Negative Positive ↓ Negative ↑

________ generation of cephalosporin can be used to treat MRSA

5th

_________ generation of cephalosporins is broad spectrum

4th

What organism are all cephalosporins inactive against?

LAME Listeria Atypical: Legionella, chlamydia, acinetobacter Mycoplasma Enterococcus

1st generation cephalosporin drugs and main use

Cefazolin Cephalexin Resistant to staphylococcal penicillinase Mainly used as a substitute for penicillin G

____________ (drugs) are used as a substitute for penicillin G

Cefazolin and cephalexin

__________ is the drug of choice for surgical prophylaxis (hint: cephalosporin)

Cefazolin (1st gen)

2nd generation cephalosporin drugs: | What organisms do they have good activity against

Cefaclor, cefoxitin, cefotetan, cefamandole H influenza, enterobacter aerogenes and some neisseria

2nd generation cephalosporins are primary used to treat ________, _______, and __________. ________ and ________ are second generation cephalosporins that can be used for prophylaxis and therapy of abdominal and pelvic cavity infections

Sinusitis; otitis; lower respiratory tract infections Cefotetan and cefoxitin

Cefotetan and cefoxitin are ________ generation cephalosporins are used for _______

2nd; Prophylaxis and therapy of abdominal and pelvic cavity infections because there is ↑ risk of gram negative bacteria being present there

What is the drug of choice for meningitis

Ceftriaxone (3rd generation cephalosporin)

What are the 3rd generation cephalosporin drugs

- ceftriaxione - cefoperazone - cefotaxime - ceftazidime - cefixime

What is the drug of choice for gonorrhea

Ceftriaxone

What are the clinical uses for ceftriaxone

- empirical treatment and prophylaxis of meningitis - gonorrhea - treatment of disseminated Lyme disease (CNS or joint infection)

Anti pseudomonas cephalosporins:

Cefaperazone and ceftazidime

What is a 4th generation cephalosporin drug and what is its route of administration

Cefipime; given IM 4th generation cephalosporin is a broad spectrum

5th generation cephalosporin and main use

Ceftaroline Given to treat MRSA

What makes treating MRSA with ceftaroline special?

Ceftataroline has a similar spectrum to 3rd generation cephalosporins so it has activity against more gram NEGATIVE pathogens too → can be used to treat skin and soft tissue infection in MRSA that are co-infected by gram negative pathogens unlike other anti-MRSA drugs like vancomycin

Most of the cephalosporins are given parententerally except ______, _______, and _______ which are given orally

Cephalexin, cefaclor, cefixime

________ and ________ cephalosporin drugs are excreted in the bile

Ceftriaxone; cefoperazone

What are some adverse effects of cephalosporins

Superinfections via C. Difficult | Kernicterus in pregnant women due to ceftriaxone

________, __________ and _______ are cephalosporins that contain methyl-thiotetrazole group and this can cause 2 specific adverse reactions:

Cefamandole, cefoperazone, cefotetan - hypoprothombinemia (give vitamin K1 to treat) - disulfiram like reactions (avoid alcohol)

What are the carbapenem drugs and what makes them special and method of administration

- Doripenem - Ertapenem - Imipenem - meropenem Resists hydrolysis by most β lactamases IV

Carapenems a very broad spectrum of activity and can be used to treat infections by P. Aeruginosa but __________ is one that cannot be used to treat Pseudomonas aeruginosa

Ertapenem

Can carbapenems be used to treat MRSA?

risks associated with carbapenem drug metabolism

Imipenem is metabolized by a special anezyme and forms a potentially toxic metabolite Doripenem, Ertapenem and meropenem are not metabolized by the same drug

What drug is given with imipenem and why?

Cilastatin, a dehydrodpeptidase I inhibitor to prevent nephron toxicity and ↑ availability

Cilastatin inhibits ___________

Dehydropeptidase I

High levels of Imipenem can cause __________

CNS toxicity e.g. seizures

What drug is a monobactam and what makes monobactams special?

Aztreonam - they have the least least cross - allergenicity with pencillin

Monobactams are effective against __________

ONLY aerobic gram NEGATIVE rods (including pseudomonas)

Are monobactams resistant to β lactams?

Yes

Main clinical application for monobactams

Used to treat gram negative infections in patients that are allergic to penicillin

Vancomycin is active against _______

Gram positive ONLY but specially effective against multi drug resistant organisms can not pass through cell wall of gram negative

Mechanism of action of vancomycin

Binds to D-Ala-D-Ala terminus of the peptidioglycan → inhibits the cell wall synthesis and peptidoglycan formation

Is vancomycin susceptible to β lactamase

Cause of resistance to vancomycin is _______

Modification of D-Ala-D-Ala binding site to D- Lactate | Plasmid mediated changes in drug permeability

Vancomycin is given with an aminoglycoside for empiric treatment of ____________

Infective endocarditis

Vancomycin is used to treat _____________

MRSA and beta lactam resistant gram POSITIVE organisms

Vancomycin is given orally for the treatment of _________ or antibiotic associated __________

Staphylococcal enterocolitis; pseudomembranous colitis (C. Difficile)