Antibiotics_WalworthPilch Flashcards
MBC (minimal bacteriacidal concentration) - YES within therapeutic range of drug
Bacteriacidal (cell-wall active agent) - Rifampin, quinolones
Toxic Dose/Effective Dose
Therapeutic Index
Therapeutic Index >1 __
Therapeutic Index
Susceptibility
Resistance
Timeline of Antibiotic Drug Therapy
- Prophylactic (no infection) -> Pre-emptive
- Empiric (after infection, cultures of blood/infection site + lab techniques [gram stain/strep test]) - single, broad spectrum agent [causative microorganism NOT yet defined]
- Definitive - Specific and narrow-spectrum agent
[causative microorganism YES defined]
Type of empiric therapy used to:
INCREASE antimicrobial activity for specific infection
DECREASE resistance + host toxicity
Combination Therapy
Combination Therapy Criteria
Usually use two agents that differ in mechanism (SIGNIFICANTLY lowered frequency of resistance)
What disease do you especially use combination therapy?
Tuberculosis
COMBINATION THERAPY: Relationship between bacteriostatic and bacteriacidal drugs
Bacteriostatic (Tetracyclins) ANTAGONIZE bacteriocidal (beta-lactams, rifampin, quinolones, aminoglycoside)
COMBINATION THERAPY: Relationship between combined usage of bacteriacidal drugs
Synergistic (one drug potentiates the inhibitory effect of the other)
Additive (one drug independent of action of other drug)
MIC (minimal inhibitory concentration) - YES, within therapeutic range of drug
MBC (minimal bacteriacidal concentration) - NO within therapeutic range of drug
Bacteriostatic agent (protein synthesis inhibitors)
MDR
Multi-drug resistant bacteria
4 Genetic Mechanisms of Developing Antibiotic Resistance
- Transformation - uptake of DNA from environment
- Transduction - uptake of DNA from bacteriophage (viral vector)
- Conjugation - transfer of plasmid from one bacterial cell to another by direct contact and pilus formation
- Transposition - for the antibiotic resistance gene to be phenotypically expressed by the bacteria, the gene has to be transferred from the plasmid to the bacterial chromosome (via insertion sequences)
beta-lactam antibiotics
penicillin (subclass: amoxicillin), methicillin, oxacillin, nafcillin, ampicillin + cephalosporins
AMINOGLYCOSIDE Antibiotics
Gentamicin Neomycin Amikacin Tobramycin Streptomycin Kanamycin
beta-lactamase inhibitor
- beta-lactamase: bacteria evolved and acquired mutation in beta-lactamase that cleaves/renders inactive beta-lactams (penicillin/cephalosporin)
- CLAVULANIC ACID
Combination Therapy: Amoxicillin (beta-lactam) + Clavulanic acid (beta-lactamase inhibitor)
Augmentin
Most common anti-fungal agent and its action
5-flucytosine
Action: Inhibits formation of dTMP -> Decreases fungal DNA synthesis
Caveat: Requires 3 metabolic enzymes to work - cytosine deaminase, UMP pyrophosphorylase, ribonucleotide reductase
Resistance to 5-flucytosine (anti-fungal agent) is most likely due to __
Downregulation of UMP PYROPHOSPHORYLASE - Enz required for the conversion of 5-flucytosine to a more active compound and its effect of decreasing fungal dTMP (DNA) synthesis
Combination Therapy: Sulfonamide + Trimethoprim (Synergistic Relationship)
Block 2 steps within the same pathway
Bactrim
Only time that bactrim will not work:
Mechanism of bacteria developing bactrim resistance
Overproduction of p-aminobenzoic acid (PABA): Increased flux of reacting metabolite to overcome competitive, antagonistic drug sulfonamide (part of bactrim)
LARGEST GROUP of ANTIBIOTICS = cell wall inhibitors
[ALL BACTERIACIDAL by weakening cell wall -> bacteria rupture by osmotic lysis]
beta-lactams (penicillin/amoxicillin + cephalosporins)
NOT beta-lactams (vancomycin)
carbapenems
monobactams
Mechanism in which bacteria acquired VRE (mostly enterocci and moderately in staphylococci)
Bacteria acquired DNA to produce a mutational proteoglycan matrix of the cell wall: 3 genes (VanHAX operon) that encoded for D-Ala-D-lactate (instead of D-Ala-D-Ala, target of vancomycin) -> Vancomycin can NO LONGER BIND
Resistances of S. aureus
1) PENICILLINASE - Resistant to penicillin
MRSA - methicillin resistant S. aureus (methicillin = “penicillinase-resistant” anti-staphylococcal beta-lacftams
2) VISA / VRSA - vancomycin intermediate/resistant S. aureus
beta-lactamase resistant penicillins (beta-lactam)
Nafcillin
Macrolide used to treat Chlamydia AND also gonorrhea or neonatal conjunctivitis (N. gonorrheae infections)
We have to assume Chlamydia co-infection whenever patient has gonorrhea
Azithromycin
Erythromycin
Clarithromycin
Telithromycin
N. gonorrheae is resistant to which antibiotics
Penicillin
Tetracycline
Quinolones
Reason: 20-30% of new gonorrhea cases are PPNG (penillinase-producing)/ TRNG (tetracycline resistant)/ QRNG (quinolone resistant)
2 IV aminoglycoside antibiotics used to treat SERIOUS infections
Gentamicin
Tobramycin
2nd line agent used to treat tuberculosis = __
What drug is this antibiotic combined with __
Streptomycin
Combined with INH or Rifampin - To prevent emergence of drug resistance
Aminoglycoside drug used when bacteria develops inactivating enzymes against tobramycin and gentamycin
Amikacin
Topical aminoglycoside antibiotics used to treat skin/eye
Neomycin
Kanamycin
Most NEPHROTOXIC aminoglycoside inhibitors when administered >5 days, elderly, renal insufficency
Gentomicin
Neomycin
Tobramycin
Most OTOTOXIC (inner ear) aminoglycoside antibiotics with
AUDITORY manifestation
* Tinnitus + high-frequency hearing loss
Kanomycin
Amikacin
Neomycin
Most OTOTOXIC (inner ear) toxic aminoglycoside - with
VESTIBULAR manifestation
* Vertigo/ataxia
Streptomycin
Gentomicin
Bacteriostatic drug used to treat Gm+ Gm- aerobic anaerobic, non Gm+/Gm- [chlamydia, rickettsia, mycoplasma], protozoa [ameba]
Aminoglycosides
Doxycycline - most common
Fluoroquinolones block ___ in Gm- bacteria
Fluoroquinolones block ___ in Gm+ bacteria
Gm-: DNA gyrase (Topo II)
Gm+: Topo IV
When all other tetracyclines fail due to antibiotic resistance, the tetracycline of choice in the hospital setting is ___
* Not resistant to bacteria - VRE/MRSA
Tigecycline (IV)
Reason for preference of doxycycline over tetracycline
1) Longer half-life: doxycycline [BID] versus tetracycline [TID]
2) Higher absorption: 100% for doxycycline + minocycline versus lower percentage for tetracycline
Contraindications of doxycycline usage
1) Younger children Bound deposits in teeth and bones -> Interferes with growth (stature) + Teeth discoloration
2) Avoid dairy products + supplements + antacid tablets - Contain multivalent cations that doxycycline can bind to
Treatment of choice for Lyme Disease
Doxycycline
SECOND LARGEST GROUP of ANTIBIOTICS = PROTEIN SYNTHESIS INHIBITORS (bacterial protein synthesis via 30S or 50S subunit)
30S inhibitors - Aminoglycosides (BACTERIACIDAL) + Tetracyclines (BACFTERIOSTATIC)
50S inhibitors - Macrolides + Clindamycin + Streptogramins + Linezolid
THIRD LARGEST GROUP of Antibiotics Part 1 = anti-DNA REPLICATION (DNA gyrase [Topo II] + Topo IV inhibitors)
[BACTERIACIDAL]
Fluoroquinolones (Ciprilfloxacin -oxacins)
THIRD LARGEST GROUP of ANTIBIOTICS Part 2= anti-METABOLITES [anti-DNA biosynthesis]
Anti-biosynthetic drugs used to block folate metabolism
SULFONAMIDES + TRIMETHOPRIM - Both work synergistically (in the same pathway) in inhibiting enzymes required for the biosynthesis of purines (A/G)
MINOR GROUP of Antibiotics = anti-CELL MEMBRANE (inner membrane)
Polymyxins + Daptomycin
* Cell membrane inhibitors are seldom used bec of high toxicity* - Difficult to get specificity for bacterial cell membrane (very similar to human membrane)
TETRACYCLINES Antibiotics (30S inhibitor)
Tetracycline Oxytetraycline Doxycycline Tigecycline Minocycline Demeclocycline
MACROLIDE Antibiotics (50S Inhibitor)
Erythromycin
Azithromycin
Telithromycin
Clarithromycin
Most common clinically used lincosamide and oxazolidinone (both 50S inhibitors)
Clindamycin
Linezolid
STREPTOGRAMIN Antibiotics (50S inhibitor)
Quinupristin
Dalfopristin
2 Possible antibiotics used to treat community-acquired PNEUMONIA (both have equal efficacy)
Tetracycline [Doxycyline]
Macrolide [Azithromycin, Clarithromycin]
2 Drugs that can be used to treat Chlamydia infections
Tetracycline [Doxycycline]
Macrolides [Azithromycin/Clarithromycin]
Only condition that TELITHROMYCIN (macrolide) is approved for __. Why is it not approved for other conditions?
Community-acquired pneumonia
Scare of cholestatic hepatitis (hepatotoxicity) with telithromycin usage
Most common bacterial infection in skin/soft-tissue
Staphylococcus
MOST effective antibiotic for acne
Clindamycin (Gm+)
MOST effective antibiotic administered ONLY by IV for VRE E. faecium + skin infections caused by methicillin-sensitive S. aureus (MSSA)
STREPTOGRAMINS - Quinupristin/Dalfopristin
Preferred antibiotic for any MDR Gm+ bacterial infection
#1 antibiotic used to treat MRSA systemic infections
VRE, penicillin-resistant streptococci
Linezolid
Is bactrim bacteriostatic or bacteriacidal?
BacteriaCIDAL although its components (trimethoprim and sulfonamide individually are bacteriaSTATIC)
Sulfasalazine is primarily used to treat ___
ulcerative colitis + enteritis
UTIs can be treated by ___
Which is the most effective?
All DNA-synthesis inhibitor antibiotics:
Sulfonamides, Trimethoprime, TMP-SMX[bactrim/septra], Fluoroquinolones
Bactrim = most effective
What is the course of treatment for bactrim? (How long do you administer bactrim?)
Toxicity of bactrim if administered >5 days
Bactrim starts to act on the human THF synthesis and thus human DNA synthesis (purines) -> Hematologic effects
MEGALOBLASTIC ANEMIA + LEUKOPENIA
Toxicity of Sulfa Drugs
1) #1 HYPERALLERGENIC - immune response that results in rash, fever, photosensitivity
2) LOW SOLUBILITY causing crystalluria and possibly hematuria
Front-line antibiotic treatment for anthrax
Fluoroquinolone - Ciprofloxacin
3 Respiratory FQs mainly used and is effective for treatment of upper and lower respiratory tract infections (Pseudonomonal infections for cystic fibrosis patients)
Levofloxacin
Gemifloxacin
Moxifloxacin
2 Flouroquinolone Drugs that are PARTICULARLY effective against Gm+ bacteria (although it is also bacteriacidal against Gm- as well)
GEMifloxacin
MOXifloxacin
4 REMAINING fluoroquinolone drugs that are PARTICULARLY effective against Gm- bacteria and mildly against Gm+ bacfteria
LEVofloxacin
LOMefloxacin
OFlofloxacin
CIPROfloxacin
Treatment for ALL stages of syphilis
Penicillin
Treatment option for Chlamydia infection manifestation of Trachoma (leading cause of blindness) + STI
Macrolides (azithromycin) OR tetracyclines (doxycycline) WITH
Ceftriazone (cephalosporin) - SINCE YOU ALWAYS ASSUME CO-INFECTION WITH GONORRHEA
Which antibiotic can you NOT administer to neonates with neonatal conjunctivitis due to a Chlamydia trachomitis infection?
Which form do you give then?
TOPICAL macrolide - NO
ORAL macrolide - YES
Bacterial infection that produces maculopapular rash (prominent in soles of hand and feet)
Syphilis - Treponema Pallidum
Bacterial infection that produces a rash that SPARES the hands/feet and spreads centrally outwards
Rickettsia prowazekki
Bacterial Infection that causes a rash that begins in the extremities and spreads centrally with fever/headache/myalgia
Rickettsia rickettsii
