Antibiotics Drugs

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Bacteriocidal Vs Bacteriostatic

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Bacteriocidal = kills the cells

Bacteriostatic = Doesn't kill cells but inhibits growth.

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Concentration-dependent killing

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the more the drug concentration exceeds the MIC (minimun inhibitory concentration), the greater the rate of killing

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Time-dependent Killing

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Once a drug concentration exceeds 4X the MIC, the rate of killing is independent of the drug concentration

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Types of Antibiotics

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1. Cell-wall synthesis inhibitors
2. Protein synthesis inhibitors
3. Agents affecting nucleic acid metabolism
4. Antimetabolites
5. Agents affection membrane permeability

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Cell Wall synthesis inhibitors

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Penicillins, cephalosporins, carbapenems, Aztreonam, Vancomycin, Telavancin, Bacitracin, Cycloserine, Fosfomycin

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Protein Synthesis Inhibitors -50S

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Erythromycin, Clarithromycin, Azithromycin, Telithromycin, Clindamycin, Quinupristin/Dalfopristin, Linezolid, Chloramphenicol

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Protein Synthesis Inhibitors -30S

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Tetracycline, minocycline, doxycycline, Tigecycline, Gentamycin, Tobramycin, Amikacin, Kanamycin, Steptomycin, Neomycin

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Agents Affecting Bacterial Nucleic Acid Metabolism

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Fluoroquinolones (Ciprofloxacin, Levofloxacin, Gatifloxacin, Moxifloxacin),Rifampin, Rifabutin

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Antimetabolites

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Sulfonamides - Sulfisoxazole, Sulfamethoxazole, Sulfasalazine, Silver sulfadiazine.
Folic Acid Reductase Inhibitor - Trimethoprim (TMP-SMZ)

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Drugs that act at the bacterial cytoplasmic membrane

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Daptomycin, Colisitn, Colistmethate, Polymyxin B

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Antimetabolites

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Sulfonamides - Sulfisoxazole, Sulfamethoxazole, Sulfasalazine, Silver sulfadiazine.
Folic Acid Reductase Inhibitor - Trimethoprim (TMP-SMZ)

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Beta lactam Antibiotics

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Penicillins, Cephalosporins, Carbapenems, Monobactams
-Beta lactam ring binds to and irreversibly inactivate penicillin binding protein transpeptidase, which is responsible for cross-linking glycopeptides strands of bacterial cell wall.
Resistance to B-lactams: B-lactamase production (hydrolyze the ring so it has no antibacterial activity), decreased diffusion of the drugs through the pores of the outer membrane of Gram negative bacteria due to decreased pore size due to expression of altered porin proteins, Altered PBPs (penicillin binding proteins).

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Penicillin Structure

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1.beta lactam ring - site on PBP binding
2. side chain R - affects acid stability, spectrum of activity and resistance to penicillinase
3. Carboxyl group

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Penicillin G

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Natural penicillin
-Binds to PBP (transpeptidase) and inhibits crosslinking of cell wall.
IV or IM, only 0% absorbed orally.
90% eliminated by kidneys rapidly. If give with probenecid, prolongs duration of action by blocking its renal secretion.
Pen G poorly penetrates into ocular, pericardial and cerebrospinal fluids (presence of memingeal inflammation allows theraputic levels of Pen G in CFS).
Adverse Effects: Allergic reactions (most common in penicillins): Maculopapular eruptions, fever
Less common: Early onset uriticaria, laryngeal edema, anaphlaxis (These are immediate hypersensitivity reactions mediated by IgE
Convulsions – with high doses

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Penicillin V

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Natural penicillin
-Binds to PBP (transpeptidase) and inhibits crosslinking of cell wall.
Similar to Penicillin G but not as readily hydrolyzed in acidic environment.
Oral use only.
Adverse Effects: Allergic reactions (most common in penicillins): Maculopapular eruptions, fever
Less common: Early onset uriticaria, laryngeal edema, anaphlaxis (These are immediate hypersensitivity reactions mediated by IgE
Convulsions – with high doses

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Methicillin

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Penicillinase-Resistant Penicillin
- only group resistant to S. aureus and S. epidermidis penicillinase.
MRSA - Methicillin resistant S. aureus. = problem.
nosocomial and community acquired MRSA - resistance due to altered PBPs w/ low affinity for B- lactams
Adverse Effects: Allergic reactions (most common in penicillins): Maculopapular eruptions, fever
Less common: Early onset uriticaria, laryngeal edema, anaphlaxis
Convulsions – with high doses

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Oxacillin

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Penicillinase-Resistant Penicillin
- only group resistant to S. aureus and S. epidermidis penicillinase.
Adverse Effects:Allergic reactions (most common in penicillins): Maculopapular eruptions, fever
Less common: Early onset uriticaria, laryngeal edema, anaphlaxis
Convulsions – with high doses

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Dicloxacillin

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Penicillinase-Resistant Penicillin
- only group resistant to S. aureus and S. epidermidis penicillinase.
Adverse Effects:Allergic reactions (most common in penicillins): Maculopapular eruptions, fever. Less common: Early onset uriticaria, laryngeal edema, anaphlaxis
Convulsions – with high doses

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Nafcillin

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Penicillinase-Resistant Penicillin
***Unlike other penicillins and is mainly excreted in bile.
- only group resistant to S. aureus and S. epidermidis penicillinase.
Adverse Effects:Allergic reactions (most common in penicillins): Maculopapular eruptions, fever. Less common: Early onset uriticaria, laryngeal edema, anaphlaxis
Convulsions – with high doses

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Ampicillin

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Amino Penicillin - Broad spectrum
-Moves into gram neg and can kill it (can still also kill gram pos)
-hydrolyzed by penicillinase and other B-lactamases
Uses: Active against Gram + and E.coli, H. influenzae, Salmonella, Shigella and some Proteus
Adverse Effects: Incomplete absorption of ampicillin can result in disturbances of the endogenous flora of the bowel --> diarrhea. Bacampicillin - ampicillin prodrug, better absorbed and has less diarrhea.

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Amoxicillin

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Amino Penicillin - Broad spectrum
-Moves into gram neg and can kill it (can still also kill gram pos)
-hydrolyzed by penicillinase and other B-lactamases
Uses: Active against Gram + and E.coli, H. influenzae, Salmonella, and some Proteus
Adverse Effects: Better absorbed than ampicillin so less likely to produce diarrhea.
Oral.

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Carbenicillin

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Antipseudomonal Penicillin
-Reserved for more serious Gram neg infections.
Resistance: hydrolyzed by penicillinase and other B-lactamases)
Removed from market in US but Carbenicillin indanyl (produg) is available
Uses: Orally for UTIs
Adverse Effects: same for all penicillins

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Ticarcillin

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Antipseudomonal Penicillin
-Reserved for more serious Gram neg infections.
Resistance: hydrolyzed by penicillinase and other B-lactamases)
Uses: spectrum similar to Ampicillin except also against indole-positive Proteus, Enterobacter and Pseudomonas
Adverse Effects: Normal penicillin ones and Impairment of platelet aggregation and coagulation, electrolyte disturbances due to high sodium content.

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Piperacillin

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Antipseudomonal Penicillin
-Reserved for more serious Gram neg infections.
Resistance: hydrolyzed by penicillinase and other B-lactamases)
Uses: active against Gram pos and Gram neg. Chief advantage is increased activity against Pseudomonas and Klebsiella

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Penicillin Adverse Reactions

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Allergic reactions (most common in penicillins- 10% of patients):
Delayed reaction: Maculopapular eruptions, fever, eosinophilia.
Less common: Early onset uriticaria, laryngeal edema, anaphlaxis (immediate reaction mediated by IgE).
Immune complexes can cause Serum sickness in some patients.
Hemolytic anemia, allergic interstitial nephritis.

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Beta -Lactamase Inhibitors

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Clavulanic Acid, Sulbactam, Tazobactam
-Irreversibly inactivate some B-lactamases and thereby prevent the inactivation of penicillins. These extend the antibacterial spectrum against organisms that had previously been resistant due to penicillinase.

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Clavulanic Acid

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Beta-lactamase inhibitor

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Sulbactam

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Beta-lactamase inhibitor

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Tazobactam

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Beta-lactamase inhibitor

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Cephalosporins

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MOA: B-lactam ring binds to PBP (transpeptidase) and blocks crosslinking of the cell wall
Resistance:resistant to Gram pos penicillinases and inactivated by broad spectrum B-lactamases
Activity: As you proceed from 1st -5th generation, flux across the outer membrane of Gram neg bacteria and stability towards Gram neg B lactamases increases.
Adverse Effects: Allergic reactions (less common than penicillins - 5%): Maculopapular eruptions, fever
Less common: Early onset uriticaria, laryngeal edema, anaphlaxis (These are immediate hypersensitivity reactions mediated by IgE
Cross sensitivity with penicillins –(pts that have had a hypersensitivity rxn with a penicillin shouldn’t take cephalosporins because they will likely have a reaction to them as well.)
High dose can cause renal damage

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Cephalexin

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First Generation Cephalosporin
Activity against Gram + cocci, e. coli, K. penumonia. Ineffective against Gram negative
Oral only

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Cefazolin

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First Generation Cephalosporin
Activity against Gram + cocci, e. coli, K. penumonia. Ineffective against Gram negative
Eliminated by renal glomerular filtration. Has longer half life.

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Cefuroxime

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Second Generation Cephalosporin
-Not as effective against Gram + as 1st gen
-Don't penetrate CSF well
Activity: against E. coli, Klebsiella, Proteus, H. infulenzae, Moraxella catarrhalis

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Cefaclor

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Second Generation Cephalosporin
-Not as effective against Gram + as 1st gen
Activity: against E. coli, Klebsiella, Proteus, H. infulenzae, Moraxella catarrhalis.
Adverse Effects: High doses can cause serum-sickness in children

-Don't penetrate CSF well

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Cefotecan

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Second Generation Cephalosporin
-Not as effective against Gram + as 1st gen
-Don't penetrate CSF well
Activity: against E. coli, Klebsiella, Proteus, H. infulenzae, Moraxella catarrhalis + Bacteroides fragilis.
-This drug is more resistant to B-lactamases.
Adverse Effects: Hypoprothrombinemia and bleeding disorders. Giving Vitamin K can prevent this. Severe disulfiram-like reaction with alcohol.

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Cefotaxime

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Third generation Cephalosporin
-Have expanded Gram neg spectrum and some penetration into CNS (meningitis).
Activity against: Enterobacteriaceae, Pseudomonas aeruginosa, serratia, neisseria gonorrhoeae and S. aureus and S. pyogenes

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Ceftazidime

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Third generation Cephalosporin
-Have expanded Gram neg spectrum and some penetration into CNS (meningitis).
Activity against: Enterobacteriaceae, Pseudomonas aeruginosa, serratia, neisseria gonorrhoeae and S. aureus and S. pyogenes

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Ceftriaxone

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Third generation Cephalosporin
-Have expanded Gram neg spectrum and some penetration into CNS (meningitis).
Activity against: Enterobacteriaceae, Pseudomonas aeruginosa, serratia, neisseria gonorrhoeae and S. aureus and S. pyogenes

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Cefepime

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Fourth Generation Cephalosporin
-Comparable to third generation but with more resistance to some B-lactamases.

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Ceftaroline

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Fifth Generation Cephalosporin
**Only B-lactam antibiotic, of any class, that has activity against MRSA!!

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Carbapenems

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Imipenem, Meropenem, Ertapenem
MOA: beta lactam ring binds to PBP (transpeptidase) and blocks cross linking of cell wall
Adverse Effects:Allergic reactions, Cross-sensitivity with penicillins and cephalosporins. Seizures with a small number of patients on Imipenem.

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Imipenem

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Carbapenem (B-lactam)
-Given with cilistatin. Cilistatin has no antibacterial activity but prevents the inactivation of imipenem by the enzyme dehydropeptidase in the kidney. Improves its efficacy in treatment of UTIs.
Activity: Widest spectrum of any B-lactam antibiotic.
Primarily used to treat nosocomial infections however resistance due to B-lactamases is increasing. MRSA and faecium are resistant.
Adverse Effects: seizures

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Meropenem

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Carbapenem (B-lactam)
-similar to Imipenem but not inactivated by dehydropeptidase

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Ertapenem

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Carbapenem (B-lactam)
-similar to Imipenem but not inactivated by dehydropeptidase

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Penicillins - mechanisms of resistance

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Natural penicillins: Beta lactamase, penicillinase, Lack of autolysins
Penicillin-resistant penicillins: Lack of autolysins
Aminopenicillins: Beta lactamase, Penicillinase, Lack of autolysins, Mutations in porin formation
Antipseudomonal Penicillins: Beta lactamase, Penicillinase, Lack of autolysins, Mutations in porin formation

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Cephalosporins - mechanisms of resistance

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1st gen: broad spectrum Beta Lactamases, lack of autolysins
2nd - 5th gen: Mutations in porin formation, lack of autolysins

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Carbapenems- mechanisms of resistance

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Beta lactamase, lack of autolysins

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Aztreonam

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Monobactam - (B lactam)
MOA: B lactam ring binds to PBP (transpeptidase) and block cell wall crosslinking
Activity: Only against aerobic Gram NEG bacteria. Excellent stability against B-lactamase.
Use: treatment of nosocomial Gram negative pathogens
Resistance:

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Vancomycin

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Glycopeptide - Cell wall synthesis Inhibitor
-Inhibits cell wall synthesis by binding to terminal D-ala D-ala portion of peptidoglycan as it emerges from cytoplasmic membrane thus inhibiting transglycosylase, preventing further elongation and cross linkage.
Resistance: Sustitution of D-ala to D-lactic acid so Vancomycin can't bind. (VRE- vancomycin resistant enterococci)
Given IV, eliminated by Kidney
Activity: Only Gram postive. Can't fit through gram neg pores.
Adverse Effects: After infusion Redman syndrome (flushing of upper body), urticaria, pruritus, hypotension, wheezing, and dyspnea. All caused by vanco-induced release of histamine. Nephrotoxicity and Ototoxicity
Uses: Narrow spectrum Gram + used to treat MRSA, antibiotic induced C. Diff enterocolitis, streptococcal endocarditis.

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Telavancin

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Lipoglycopeptides
-Inhibits cell wall synthesis by binding to terminal D-ala D-ala portion of peptidoglycan as it emerges from cytoplasmic membrane thus inhibiting transglycosylase, preventing further elongation and cross linkage.
Also has lipid tail that causes depolarization of cytoplasmic membrane.
Adverse Effects: Women of childbearing potential should have serum pregnancy test prior to administration.
Resistance: substitution of D-ala with D-lactic acid so it can't bind

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Bacitracin

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Cell wall synthesis inhibitor
-peptide antibiotic that is only used topically due to its extreme nephrotoxicity

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Cycloserine

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Cell Wall Synthesis Inhibitor
-synthetic analog of serine used in treatment of Tuberculosis. It inhibits alanine racemase thereby preventing conversion of L-alanine to D-alanine.

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Fosfomycin

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Cell Wall Synthesis Inhibitor
-inhibits synthesis at early stage
-used for UTIs

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Erythromycin

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--macrolide protein synthesis inhibitor
--binds to 23S rRNA of 50S ribosome to inhibit translocation - so inhibits protein synthesis

--narrow spectrum: Strep, Staph, Mycoplasma pneumonia, Legionella

--concentrated in the liver and excreted in the bile

--not stable in gastric acid
--may cause abdominal cramping- stimulates the motilin receptor which increases GI motility.
-Can cause cholestatic hepatitis
--can cause cholestatic hepatitis
--inhibits P450 enzymes
-Resistance: efflux pump, mutation of ribosomal binding site, methylation of ribosomal binding site.

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Clarithromycin

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--macrolide protein synthesis inhibitor
--binds to 23S rRNA of 50S ribosome to inhibit translocation
-more active against Staph and Strep and broader spectrum than erythromycin.

--excreted by the kidney

--less likely to cause GI upset compared to erythromycin
--may cause mania
-Inhibits P450s
-Resistance: efflux pump, mutation of ribosomal binding site, methylation of ribosomal binding site.

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Azithromycin

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--macrolide protein synthesis inhibitor
--binds to 23S rRNA of 50S ribosome to inhibit translocation

--tissues act as reservoir for this drug - so only given for 5 days instead of 10
--excreted in the bile

--spectrum: Staph, Strep, Mycoplasma pneumonia, chlamydia, M.avium, H.influenza

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Telithromycin

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Ketolide
--protein synthesis inhibitor
--binds to domains II and V of the 23S rRNA of the 50S ribosome
-second binding site prevents resistance due to rRNA methylation and overcomes efflux pump resistance

--treats community acquired pneumonia (CAP)

--not to be given to patients with hx of hepatitis or myasthenia gravis
- can cause acute hepatic failure and sever liver injury

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Clindamycin

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Lincosamides
--protein synthesis inhibitor
--binds the 23S rRNA of the 50S ribosome
-Oral - well absorbed
--spectrum: Many Gram + organisms, Staph, Strep, community-acquired MRSA, B.fragilis
--affinity for osseous tissues

--frequently associated with pseudomembranous colitis
--Resistance: Methylation of ribosomal binding site, mutation of ribosomal binding site

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Quinupristin/Dalfopristin

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Streptogramins
--protein synthesis inhibitors
--bind to 50S ribosome
--no cross resistance with other agents
--these two drugs are synergistic because bind at different sites
--specturm: only Gm(+), nosocomial infections; bloodstrem infection with VREF; skin infection with Staph or Strep
--metabolized by CYP3A4
Adverse Effects: venous problems at the site of infusion. Arthralgia and myalgia.

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Linezolid

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Oxazolidinones
--protein synthesis inhibitors
--bind to 50S ribosome

--oral bioavailability is close to 100%

--spectrum: only Gm(+) bac; VRE, MRSA, VISA, GISA; all enterococci; penicillin-susceptible and resistant Strep.

--may cause myelosuppression, thrombocytopenia, anemia, peripheral neuropathy and serotonin syndrome

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Chloramphenicol

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Nitrobenzene
--protein synthesis inhibitors
--bind to 50S ribosome
--Resistance: acetylation that converts chloramphenicol to an inactive metabolite

--rapidly absorbed from the GI tract (widely distributed in body fluids including CSF, bile, milk)
--conjugated in liver by glucuronosyl transferase

--only used to treat infections that cannot be treated with other antibioitics

--can cause aplastic anemia (not reversible), blood dyscrasias (reversible, dose-dependent) and gray-baby syndrome

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Tetracycline
Minocycline
Doxycycline

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--protein synthesis inhibitors
--bind to 30S ribosome
--Resistance: Efflux pump, cross resistance btwn tetracyclines

--absorption is impaired by milk and aluminum hydroxide antacid
--tetracycline and minocycline are eliminated via glomerular filtration while doxycycline is excreted in the feces (90%)

--doxycycline has a longer hal-life and doesn't accumulate in patients with compromised renal function

--spectrum: used for infectious diseases, rickettsiae, chlamydia,mycoplasmas, H.pylori, plasmodia and amebas

--may cause photoxic reaction (extreme sunburn), hepatic dysfunction (exacerbated with pregnancy), teeth discoloration, depressed bone growth, hypersensitivity and GI irritation.
Can cause teeth discoloration and bone problems in babies born to mothers on tetracyclines.
Minocycline - vertigo, dizziness

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Tigecycline

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--protein synthesis inhibitor
--binds to 30S ribosome
--similar to tetracycline but has increased affinity to the ribosomal receptor which aids in overcoming resistance due to changes in binding sites and efflux pumps.
--no cross resistance

--spectrum: MRSA, VRE, penicillin-resistant Strep; Acinetobacter resistant to imipenem and ESBL-producing enterobacteriacea
--Adverse Effects: very high incidence of nausea (34.5%) and vomiting (20%)

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Gentamicin
Tobramycin
Amikacin
Streptomycin
(Neomycin, Kanamycin)

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--aminoglycoside protein synthesis inhibitors
--binds to 30s and acts directly on the ribosome by interfereing with proper attachment of messenger rRNA to ribosomes (initiation) leading to decreased or abnormal protein synthesis
--concentration-dependent killing
--consistently bacteriocidal
--narrow therapeutic window
--Resistance due to physphorylation or acetylation into an inactive metabolite
--poorly absorbed after oral administration so give subcut or intramusc
--distributes in all extracellular fluids
--excreted by glomerular filtration (with active reabsorption)

--uptake of aminoglycosides by bacteria requires oxygen

--treat systemic infections due to Gm(-) bacteria

--amikacin may be active against some organisms that are resistant to gentamicin or tobramycin

--may cause ototoxicity and nephrotoxicity
--may cause neuromuscular blockade

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Ciprofloxacin
Levofloxacin
Gatifloxacin
Moxifloxacin

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--fluoroquinolones
--inhibit bacterial DNA gyrase in Gm(-) and topoisomerase IV in Gm(+).
Both of these cuts the DNA then rebinds it (which helps remove the supercoils for replication). FQs block the rebinding so there's just a bunch of cuts in the DNA which eventually becomes lethal.
--Resistance: mutation to A subunit of DNA gyrase, mutation to B subunit, efflux pump.
--Oral Bioavailability very high. Renal excretion.

--ciprofloxacin is most effective vs. Pseudomonas compared to other fluoroquinolones

--levo-, gati- and moxifloxacin are more active vs. Strep, including MDRSP
--Adverse Effects: GI disturbances, rash, allergic rxns, CNS disturbances (headache, vertigo, excitement, visual disturbances), Tendon ruptures with exercise. Contraindicated in children due to cartilage damage.

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Rifampin
Rifabutin

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--inhibits DNA-dependent RNA polyermase
--2nd most important drug in treatment of TB (after isoniazid)

--alone, given as prophylaxis to people exposed to N.meningitidis or carriers of N.meningitidis

--often used in combo to treat other infections like MRSA, legionella

--potent inducer of CYP3A4

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Sulfisoxazole
Sulfamethoxazole

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--antimetabolite antibiotics
--competitive inhibitors of dihydropteroate synthetase, leading to depletion of folic acid in bacteria --> inhibits DNA, RNA and protein synthesis
--Resistance: Increased PABA synthesis, altered dihydropteroate synthetase, utilization of exogenous folic acid

--absorbed rapidly after oral administration
--acetylated and excretion in the urine

--treat UTI's and nocardiosis

--Adverse Effects:most toxic effects involve skin
--Cross sensitization
Fever, blood dyscrasias, eosinophilia, cystalluria (crystals in urine), hepatitis, kernicterus in newborns due to displacement of bilirubin from albumin.

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Silver Sulfadiazine

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Sulfonamide
- inhibits dihydropteroate synthase.
--used to prevent colonization of burns by bacteria. Preventive!! Can't treat already existing infection.


--Adverse Effects:most toxic effects involve skin
--Cross sensitization
Fever, blood dyscrasias, eosinophilia, cystalluria (crystals in urine), hepatitis, kernicterus in newborns due to displacement of bilirubin from albumin.

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Sulfasalazine

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Sulfonamide
--inhibits dihydropteroate synthase
--not used to treat bacterial infections. Used to treat ulcerative colitis.


--Adverse Effects:most toxic effects involve skin
--Cross sensitization
Fever, blood dyscrasias, eosinophilia, cystalluria (crystals in urine), hepatitis, kernicterus in newborns due to displacement of bilirubin from albumin.

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Trimethoprim (TMP)

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--antimetabolite antibiotic
--inhibits dihydrofolate reductase, which blocks dihydrofolate reduction to tetrahydrofolate

--TMP + SMZ (sulfamethoxazole) exerts a synergistic and bactericidal effect
--TMP/SMZ : good for UTIs, systemic infections (URT, Soft tissue,etc). Treats bronchitis, otitis media.
Drug of choice for pneumonia due to Pneumocystis jiroveci.
Many AIDS patients can't tolerate this so take Pentamidine.'
--Adverse Effects: TMP can interfere with folate metabolism in malnourished individuals can cause megaloblastic anemia, leukopenia and granulocytopenia.

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UTI antiseptics

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Nitrofurantoin, Methenamine, Fosfomycin
--Have no systemic activity but only act in the urinary tract.
--Rapid elimination, high protein binding and requirement for low pH (why they only work in urinary tract)

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Nitrofurantoin

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--urinary tract antiseptic
--no systemic activity and rapidly excreted by kidney

--treats acute cystitis and is a UTI prophylaxis

--serious toxic effect involves lungs (chills, cough, pulmonary infiltrations--> pulmonary fibrosis). Also causes GI disturbances and headache

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Methenamine

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UTI antiseptic
--breaks down into ammonia and formaldehyde which is antibacterial.
-- Used for prophylaxis to prevent recurrence of cystitis (bladder infection

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Fosfomycin

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UTI antiseptic
--inhibits stage 1 of cell wall synthesis.
--Treatment of uncomplicated urinary tract infections (acute cystitis) in women due to susceptible strains of E. coli and E. faecalis

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Daptomycin

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--acts at bacterial cytoplasmic membrane
--binds to cell membane of Gm(+) bac and disrupts cell membrane potential by forming pores, allowing K+ ions to leak out

--concentration dependent killing --> creates more pores --> increased killing

--spectrum overlaps vancomycin except maintains activity against relevant organism with decreased susceptibilty to vancomycin.
Active against MRSA, VRSA, VRE

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Colistin
Colistimethate
Polymyxin B

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--act at bacterial cytoplasmic membrane
--have lipophilic and lipophobic groups and penetrate cell membranes and quickly disrupt the membranes of broad array of Gram Neg aerobic bacilli.
--Rapidly bactericidal
--Concentration-dependent killing

--fell into disuse by 1980 b/c of nephrotoxicity

--occasionally needed to treat Pseudomonas and other resistant Gm(-) bac

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Metronidazole (Flagyl)

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--miscellaneous antibiotic
--bacteria reduce its nitro group to generate free radicals which damage DNA

--antiprotozoal agent but effective against. anaerobic bac like C.difficile, H. pylori, B. fragilis
--Drug of choice to treat C. diff

-may cause metallic taste, headache or disulfuram-like reaction with alcohol

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Spectinomycin

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Miscellaneous Antibiotic
--Alternative drug to N. gonorrhea including penicillinase-producing strains in patients allergic to other drugs

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Fidaxomicin

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Miscellaneous Antibiotic
--Treatment of C. difficle-associated diarrhea.

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Anti-tuberculosis Drugs

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Isoniazid, Rifampin, Pyrazinamide, Ethambutol, Streptomycin
--All taken orally except Streptomycin which is IV
--cornerstone of TB treatmetn is use of Multi-Drug Regimens because its very easily becomes resistant to one drug. Each drug should have a different MOA. Each drug should have different activities against different populations of TB.

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Isoniazid

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--primary agent in treatment of TB
--only drug approved for prophylaxis of TB
--bacteriocidal for growing organisms and bacteriostatic for resting organisms.
--needs to be activated by catalase/peroxidase enzyme (mutation of this = resistance)

--rate limiting step for its elimination is acetylation, making a patient's acetylator status very important

--may cause peripheral neuropathy like that of vitB6 deficiency
--may cause hepatotoxicity (isoniazid-induced hepatitis)

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Rifampin

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-second most important Drug in treatment of TB
-- inhibits DNA dependent RNA polymerase

--Also treats Leprosy

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Ethambutol

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--treats mycobacterial infections
--may cause ocular toxicity (loss of acuity, decreased visual fields and loss of red/green color) and hyperuricemia --> gout

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Pyrazinamide

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--treats mycobacterial infections
--dose-related hepatotoxicity in 1-5%, hyperuricemia --> gout

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Drugs Used to treat Leprosy

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Dapsone, Clofazimine, Rifampin

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Dapsone

Back 86

Treats Leprosy
--Inhibits folic acid synthesis

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Clofazimine

Back 87

Treats Leprosy
--may interfere with the replication of bacterial DNA, but MOA is unknown

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Antibiotics and organisms involved in resistance due to altered penicillin binding protein

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Classes: Penicillins, Cephalosporins, Carbapenems, Monobactams
Bacteria: MRSA, S. pneumonia

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Antibiotics and organisms involved in resistance due to Beta lactamases

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Classes: Penicillins (except Methicillin, Oxacillin, Dicloxacillin, Nafcillin), Cephalosporins (Resistance increases with class number), Monobactams
Bacteria: Bacteroides fragilis, S. aureus, S. epidermis, H. influenza, Legionella

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Antibiotics and organisms involved in resistance due to penicillinase production

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Penicillins except: Methicillin, Oxacillin, Dicloxacillin, Nafcillin Transduction in staph aureus. S. epidermis

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Antibiotics and organisms involved in resistance due to alterations in porin size

Back 91

Any gm negative: Penicillins (Ampicillin, Amoxicillin, Carbenicillin, Ticarcillin, Piperacillin); Cephalosporins (Cefotaxime, Ceftazidime, Ceftriaxone, Cefepime), Monobactams, Flouroquinolones

Front 92

Antibiotics and organisms involved in resistance due to acquiring genetic material from the environment

Back 92

S. pneumoniae and N. meningitides

Front 93

Antibiotics and organisms involved in resistance due to Substitution of terminal residue in peptidoglycan chain:

Back 93

Classes: Vancomycin, Telavancin. Bacteria: Enterococci

Front 94

Antibiotics and organisms involved in resistance due to bacterial efflux pump

Back 94

Classes: Tetracyclines, Macrolides (Erytrhomycin, Clarithromycin, Azythromycin), Fluoroquinolones. Bacteria: Pseudomonas Aeruginosa

Front 95

Antibiotics and organisms involved in resistance due to mutation of ribosomal binding site

Back 95

: Classes: Macrolides (Erytrhomycin, Clarithromycin, Azythromycin)

Front 96

Antibiotics and organisms involved in resistance due to methylation of ribosomal binding site

Back 96

Classes: Macrolides (Erytrhomycin, Clarithromycin, Azythromycin), Clindamycin

Front 97

Antibiotics and organisms involved in resistance due to acetylation of drug

Back 97

Classes: Aminoglycosides ( Gentamicin, Tobramicin, Amikacin), Chloramphenicol

Front 98

Antibiotic and organism involved in resistance due to phosphorylation of drug

Back 98

Classes: Aminoglycosides ( Gentamicin, Tobramicin, Amikacin)

Front 99

Antibiotic and organism involved in resistance due to mutations in DNA gyrase

Back 99

Classes: Flouroquinolones
Bacteria: E. Coli and many other Gm -

Front 100

Antibiotic and organism involved in resistance due to m) Increased PABA synthesis, alteration in dihydropterate synthetase, utilization of exogenous folic acid (all the same drug)

Back 100

Sulfonamides: Sulfisoxazole, Sulfamethoxazole, Silver Sulfadiazine, Sulfasalazine

Front 101

Which antibiotics must be dose-adjusted in renal failure?

Back 101

Penicillin G, Vancomycin, Aminoglycosides ( Gentamicin, Tobramicin, Amikacin) Fluoroquinolones

Front 102

Which antibiotics induce cytochrome CYP3A4 metabolism of drugs?

Back 102

Inducer: Rifamycins (Rifampin, Rifabutin)

Front 103

Which drugs inhibit cytochrome CYP3A4 metabolism of drugs?

Back 103

Inhibitors of 3A4: Erythromycin, Clarithromycin

Front 104

Which drugs or drug classes would be most affected by changes to this cytochrome?

Back 104

Affected: Quinupristin/Dalfopristin

Front 105

Which antibiotics cause suppression of bone marrow function/blood dyscrasias?

Back 105

Linezolid, CHLORAMPHENICOL (THE BIG ONE), Sulfonamides: Sulfisoxazole, Sulfamethoxazole, Silver Sulfadiazine, Sulfasalazine

Front 106

Which antibiotics cause renal failure?

Back 106

High doses of cephalosporins, Bacitracin, Aminoglycosides ( Gentamicin, Tobramicin, Amikacin)

Front 107

Which antibiotics cause hearing loss?

Back 107

Vancomycin, Aminoglycosides ( Gentamicin, Tobramicin, Amikacin)

Front 108

Which antibiotics should never be given to newborns?

Back 108

--Sulfonamides: Sulfisoxazole, Sulfamethoxazole, Silver Sulfadiazine, Sulfasalazine and chloramphenicol -kernicterus (bilirubin in brain). --Chloramphenicol - gray baby syndrome.

Front 109

What antibiotics should not be given to pregnant women or anyone younger than 8 years old?

Back 109

Tetracyclines --> causes yellowing of teeth and messes up bone development in kids, fetus

Front 110

12) Which antibiotics must be given as a combination of 2 drugs to be effective?

Back 110

--Imipenem with Cilistatin to prevent metabolic inactivation of imipenem by dehydropeptidase
--Quinupristin/Dalfopristin
--Cell wall synthesis inhibitors and aminoglycosides
--Sulfanamides and folic acid reductase inhibitors

Front 111

Which antibiotics cause depolarization of the cytoplasmic membrane?

Back 111

Telavancin

Front 112

Which antibiotic classes cross-react in allergic patients?

Back 112

Penicillins and cephalosporins, Tetracyclines, Sulfonamides

Front 113

Which antibiotic is also used to promote gastric motility?

Back 113

Erythromycin

Front 114

What antibiotics are only useful for gram positive infections (No gram negative coverage)

Back 114

Vancomycin, Telavancin, Bacitracin, Daptomycin, Quinupristin/ Dalfopristin, Linezolid

Front 115

What antibiotics increase the risk of tendon rupture?

Back 115

Fluoroquinolones: Ciprofloxacin, Levofloxacin, Gatifofloxacin, Moxifloxacin

Front 116

What antibiotics can cause folate deficiency?

Back 116

Trimethoprim

Front 117

21) Describe the common characteristics, infectious pathogens, and recommended treatment of human vs. animal bite wounds

Back 117

Pathogens in bites: anaerobes and facultative anaerobes found as normal flora in mouth. Must treat anaerobic and aerobic pathogens.
Animal: Pasteurella multocida
Human: Bacteriodes, Fusobacterium, Peptostreptococcus, Eikenella corrodens, S. aureus, Viridans streptococci. Require admission to hospital if clench fist injury.

Front 118

Differentiate simple vs. uncomplicated UTI in terms of pathogens, clinical workup, and empiric treatment

Back 118

Simple: premenopausal, sexually active women
--Pathogen: E. Coli
--Minimal work up
--Tx: TMP-SMX , FQ or Nitrofurantoin

Complicated: men, hospitalized ptnt, advanced age and debility, fctl and anatomical abn of urinary tract, pregnancy, diabetes
--Pathogen: Non E.coli Enterobacteriaceae, P. Aeruginosa, E. Faecalis