Infectious Dz - Antibiotic Review Flashcards
What do bacteriostatic antibiotics do?
They stop bacterial growth by interfering with protein synthesis and metabolism
What do bactericidal antibiotics do?
The kill bacteria by interfering with cell wall or nucleic acid synthesis
What antibiotics are bacteriostatic?
Chloramphenicol, sulfanomides, trimethoprim, clindamycin, doxycycline, and macrolides
What antibiotics are bactericidal?
Beta-lactams, fluoroquinolones, aminoglycosides, Timethoprim sulfas (which is the combo of sulfanomides and trimethoprim), vancomycin, and metronidazole
When will the classification of an antibiotic (static or cidal) influence your choice of antibiotic?
If there are life-threatening infections or an immunocompromised individual
What is the minimum inhibitory concentration (MIC)?
The lowest concentration of an antimicrobial that will inhibit bacterial growth
What factors does the in vitro value not take into account?
In vivo factors - Antibody in the serum, urine, and bile, pH of the infected environment, and presence of biofilms
What is efficacy of an antibiotic related to?
the amount of time that the antibiotic concentration is above the MIC
What maximizes efficacy of antibiotics?
Multiple daily doses, continuous administration, OR giving a single daily (high) dose
What antibiotics are time-dependent?
Penicillins, cephalosporins, carbapenems, macrolides, lincosamides, and tetracyclines
What antibiotics are concentration dependent?
Fluoroquinolones, aminoglycosides, and metronidazole
What four antibiotics/groups are part of the beta lactam structural group?
Penicillins, cephalosporins, carbapenems, and monobactams
Are the beta lactams cidal or static? Time or concentration dependent?
Cidal and time-dependent
How do beta lactams work?
They block cell wall synthesis by inhibiting penicillin-binding proteins
How are beta lactams metabolized?
They are renally excreted - high concentrations in the urine
What forms of penicillin do we use in small animals?
Amoxicillin/ampicillin and Ticarcillin
What is the spectrum of activity of penicillins?
Excellent activity against Gram + and anaerobes
Some gram - efficacy
Not effective against Pseudomonas
What enzyme do gram - bacteria produce that inactivates beta-lactam antibiotics?
Beta lactamase
What can extend the efficacy of penicillins against beta lactamase inhibitors?
Clavulanic acid (Clavamox) and Sulbactam (Unasyn)
What generation of cephalosporins has the most activity against gram negative organisms?
4th generation - activity increases with the generation
What is the spectrum of cephalosporins?
Effective against Gram positives
Resistant to all Gram + beta-lactamases
What carbapenems are used in small animal medicine?
Imipenem and Meropenem
What ‘effect’ do carbapenems have that other beta-lactams don’t have?
a post-antibiotic effect
What are Carbapenems effective against?
Gram negative and positive bacteria - there is little resistance as of now because these drugs are reserved for serious infections (the big guns)
How are Carbapenems formulated?
In IV and SQ routes because there is poor oral absorption
Uses of Carbapenems should be limited to what?
Serious multi-drug resistant gram - infections and in immunocompromised individuals
What glycopeptide do we use in small animal medicine?
Vancomycin
Is Vancomycin static or cidal? Time or concentration dependent?
Cidal and time-dependent
How do glycopeptides work?
They inhibit cell wall synthesis by binding amino acids used in its synthesis
How are glycopeptides formulated?
IV due to poor oral absorption
When is it recommended to use glycopeptides?
Only for multi-drug resistant gram + infections - Clostridium difficile and Methicillin-resistant Staph infections
What are the adverse effects of glycopeptides?
Red man syndrome (humans) and nephrotoxicity
Are fluoroquinolones cidal or static? Time or concentration dependent?
Cidal and concentration-dependent
How do fluoroquinolones work?
They cause disruption of DNA synthesis by inhibition of DNA gyrase and topoisomerase IV
What fluoroquinolones do we use in small animal medicine?
Marbofloxacin, enrofloxacin, ciprofloxacin, and pradofloxacin
What is the spectrum for fluoroquinolones?
Gram - bacteria, but also effective against + at higher doses
Poor efficacy against anaerobes
Attains high intracellular concentration which is good for Mycoplasma
What infections are fluoroquinolones good for and why?
They are highly lipophilic which provides for excellent penetration for prostatic and respiratory infections
What are the adverse effects of enrofloxacin in cats?
Acute retinal degeneration
What is a safer fluoroquinolone in cats?
pradofloxacin
What adverse effects do fluoroquinolones cause in young animals (4-28 weeks)?
Cartilage/joint toxicity
What does pradofloxacin cause when given in high doses in dogs?
Myelosuppression
Is metronidazole static or cidal? Time or concentration dependent?
Cidal and concentration dependent
How does metronidazole work?
It is a prodrug that is activated in the bacterial cytoplasm to a free radical that causes DNA damage
What is the spectrum of metronidazole?
It is especially effective against anaerobes (both gram + and - ) and protozoans (Giardia)
What are the adverse effects of metronidazole?
Neurotoxicity with higher doses - there are generally vestibular signs
True or False: Sulfonamides are always combined with trimethoprim
True
What is the MOA of trimethoprim-sulfonamide (TMS)?
Synergistic inhibition of folate metabolism, resulting in inhibition of purine synthesis
What enzyme does trimethoprim produce?
dihydrofolate reductase
What enzyme does sulfonamide produce?
pteridin synthase
What are sulfonamides effective against?
Gram + and - bacteria - especially Nocardia
Protozoal organisms
Variable efficacy against anaerobes
Where do sulfonamides have excellent penetration?
in prostatic tissue
Where are sulfonamides in high concentration?
urine
What are the adverse effects of sulfonamides?
KCS, immune-mediate thrombocytopenia, hemolytic anemia/aplastic anemia, polyarthritis, hepatotoxicity, and bone marrow suppression
How should you monitor for adverse effects of sulfonamides?
Shirmer tear test, liver panels, and CBC
What aminoglycosides do we use in small animal medicine?
Amikacin, gentamicin, tobramycin, and neomycin
What is the MOA of aminoglycosides?
Interfere with outer membrane LPS structure and inhibit protein synthesis by binding to the 30S ribosomal subunit
Are aminoglycosides static or cidal? Time or concentration dependent?
cidal and concentration dependent
What organs do the aminoglycosides have poor penetration into?
The prostate, brain/CSF, and the eye
What is the spectrum of aminoglycosides?
Excellent gram - activity, good gram + activity
Anaerobes have intrinsic resistence
How are aminoglycosides formulated?
SC, IM, IV, or topical administration because there is poor oral administration
Where are aminoglycosides excreted?
in the urine
What are the adverse effects of aminoglycosides?
Nephrotoxicity and ototoxicity
What chloramphenicols are used in small animal medicine?
Chloramphenicol, florfenicol and thiamphenicol
What is the MOA of chloramphenicols?
Inhibits protein synthesis by binding to the 50S ribosomal subunit
Are chloramphenicols static or cidal? time or concentration dependent?
Static and time dependent
What is the spectrum of chloramphenicols?
Broad spectrum - gram +/- and anaerobes
What organs do chloramphenicols have excellent penetration?
Brain, eye, and prostate due to excellent lipid sollubility
What are the adverse effects of chloramphenicols?
Irreversible aplastic anemia in humans
Reversible bone marrow suppression
What species are chloramphenicols poorly tolerated in?
cats - they get GI signs and BM suppression
What tetracyclines do we use in small animal medicine?
tetracycline, doxycycline, and minocycline
Are tetracyclines static or cidal? Time or concentration dependent?
Static and time dependent
What is the MOA of tetracyclines?
Inhibits protein synthesis by binding 30S ribosomal subunit
What is the spectrum of tetracyclines?
Gram + and - intracellular bacteria (rickettsiae) and spirochetes
What are the adverse effects of tetracyclines?
vomiting, esophagitis and esophageal strictures in cats, hepatopathy, and possible dental discoloration with use of doxy
What lincosamides do we use in small animal medicine?
Clindamycin and lincomycin
Are lincosamides static or cidal? Time or concentration dependent?
Static and time dependent
What is the MOA of lincosamides?
inhibits protein synthesis by binding to 50S ribosomal subunit
What is the spectrum of lincosamides?
Gram postitives, anaerobes, and protozoans
What are the adverse effects of lincosamides?
Esophagitis in cats
What macrolides do we use in small animal medicine?
Erythromycin, tylosin, clarithromycin, and azithromycin
Are macrolides static or cidal? Time or concentration dependent?
Static and time dependent
What is the spectrum of macrolides?
Gram +, some gram -, and mycobacterium (clarithromycin)
What macrolide is good for antibiotic resistant diarrhea?
tylosin
Are fungi eukaryotes or prokaryotes?
eukaryotes
What antifungals do we use?
Azoles, amphotericin B, 5-flucytosine, and terbinafine
What imidazoles do we use in small animal medicine?
Ketoconazole, clotrimazole, and enilconazole
What triazoles do we use in small animal medicine?
Itraconazole, fluconazole, voriconazole, and posaconazole
Do imidazoles or triazoles have more side effects?
imidazoles
What is the MOA of azoles?
They are fungistatic - interfere with ergosterol synthesis through inhibition of 14 alpha-demethylase
What are the adverse effects of azoles?
Inhibition of mammalian p450 Suppression of adrenal function (ketoconazole) Teratogenic Hepatotoxicity Ulcerative skin lesions (itraconazole)
What is the MOA of Amphotericin B?
Causes pores in the cell membrane by binding to sterols
Macrophage activation
Is amphotericin B static or cidal?
Static but cidal at high doses
What are the adverse effects of amphotericin B?
nephrotoxicity
What is the MOA of 5-Flucytosine?
It is a fluorinated pyrimidine that interferes with DNA replication when converted to fluorouracil
What is 5-Flucytosine effective against?
Only against Cryptococcus and Candida
Is 5-Flucytosine static or cidal?
static
Why is 5-Flucytosine never used alone?
Because resistance develops quickly when used as a single agent
What are the adverse effects of 5-Flucytosine?
Cutaneous drug eruptions (dogs) and myelosuppression
How does Terbinafine work?
It inhibits squalene epoxidase, causing intracellular accumulation of squalene
Is terbinafine static or cidal?
cidal
What is terbinafine especially effective against?
dermatophytes
What are the adverse effects of terbinafine?
Most are unknown, but it is known to cause facial pruritus in cats
You are treating a 15 year old spayed female cat with a suspected UTI. Which antibiotic would be the best choice for treatment?
a. Enrofloxacin
b. Gentamicin
c. Amoxicillin
d. Chloramphenicol
c. Amoxicillin
Not enrofloxacin because it causes acute retinal degeneration in cats
Not Gentamicin because…. not entirely sure, but it does cause nephrotoxicity
Not Chloramphenicol because it is poorly tolerated in cats
