Antibiotics Flashcards
What are the different MOA of ABs?
Affect Cell Wall:
1) Inhibition of peptidoglycan (PG) synthesis
2) Inhibition of PG cross-linking
- DNA gyrase function inhibition
- DNA integrity alteration
- mRNA synthesis inhibition
- Cell membrane integrity alteration
- Folic acid pathway alteration
- 30s & 50s inhibition
- beta lactamase inhibitors
Which ABs prevent PG synthesis?
- Vancomycin
- Fosfomycin
What ABs groups affect the cross-linking of PG and are b-lactams?
4 groups of ABs
- Penicillin (PCN)
- Cephalosporins
- Carbapenems
- Monobactam
Which ABs are part of PCN’s?
- Natural: PCN G & V
- Amino: Amoxicillin & Ampicillin
- Anti staph: Oxacillin & Dioxacillin
- Anti-pseudo: Piperacillin
Which ABs are part of Cephalosporins?
1st generation: cefezolin, cepharaxin
2nd generation: not common
3rd generation: ceftriaxone, ceftazaline, ceflataxine
4th generation: cefepine
5th generation: ceftaroline
Which ABs are part of Carbapenams?
- Remember DIME
- Doripenem
- Imipenem
- Meropenem
- Etrapenem
Which AB are part of monobactams?
- Aztranem
- great for PCN allergic patient plus very broad use
Which drugs are part of beta lactamase inhibitors? Which ABs are they combined with?
- Remember “CAST is A CAP”
- Clavabactam –> amoxicillin
- Arvibactam –> ceftazidine
- Sulbactam –> ampicillin
- Tazobactam –> piperacillin
What is the MOA of beta lactamase inhibitors?
- Penicillin binding protein (PBP, a transpeptidase) help cross link PGs in cell wall
- ABs inhibit PBP to form cross-linking of PG in cell wall
- Resistance formed against these ABs
- Bacteria produced an enzyme, beta lactamase
- Beta Lactamase break down beta lactam ring in ABs which prevents AB to bind to PBP
*Beta-lactamase inhibitors block the enzymatic degradation of beta lactam rings in the ABs
- therefore ABs can still have their bactericidal effect on bacteria
Which ABs alter bacterial cell membrane integrity? MOA?
- Bacteriocidal
- Daptomycin
- Polymixin
*introduce efflux pumps to bacterial cell to make it more permeable- leaks out ions etc and therefore lysis of cell
Which ABs alter the folic acid pathways of bacteria? MOA
-Bacteriostatic
AKA Co-trimoxazole
- Trimethoprim / Sulfamethoxazole
- often used in combo TMP-SMX
- Sulfamethoxazole: prevent conversion from PABA (para-aminobenzoic acid) to DHF (dihyrodrofolate)
- inhibition of 1st step of folic acid pathway
- Trimethoprim: decrease DHF therefore unable to convert to tetrahydrofolate (THF)
- inhibition of 2nd step of folic acid pathway
Which ABs alter Bacterial DNA integrity? MOA?
- Bacteriocidal
- Metronidazole: increase production of free radicals which break DNA strands
- Nitrofurantoin: same as above, plus causes protein damage
Which AB is inhibits the synthesis of mRNA? MOA?
- Rifampin
- MOA: inhibition of RNA polymerase enzyme
Which ABs alter DNA gyrase function? MOA?
- inhibition of DNA gyrase (aka topoisomerase type 4) enzyme
- therefore unable to cut up and re-ligate DNA leading to DNA fragmenation
- Fluroquinolones:
1st Generation: Ciprofloxacin
2nd Generation: Levofloxacin, Gemifloxacin, Moxifloxacin
*2nd Gen FQ’s are aka respiratory FQ’s
Which ABs are 50s Ribosomal inhibitors? MOA?
Bacteriostatic
MOA: inhibition of translation stage of protein synthesis on 50s subunit
Macrolides:
- Azithromycin
- Erythromycin
- Clarithromycin
- Clindamycin
- Chloramphenicol (only developing countries)
- Linezolid
Which ABs are 30s Ribosomal Inhibitors? MOA?
Bacteriostatic & Bacteriocidal
MOA: inhibition of translation stage of protein synthesis on 30s subunit
Aminoglycosides (GAT): Bacteriocidal
- gentamycin, Amikacin, tobramycin
Tetracyclines: baceriostatic
-tetracycline, doxycycline
Empiric AB therapy for pneumonia?
CAP: Strep Pne. H. Influ. Atypical
- FQ’s e.g. ciprofloxacin
- Ceftriaxone (+/- doxycycline)
- Azithromycin
- Cefuroxime
HAP: (after 48 hours admission)- MRSA, Pseudomonas, E.coli
- Vancomycin
- Anti Pseudo PCN e.g. Piperacillin
- Ceftriaxone
- AG’s e.g. gentamycin
Empiric AB therapy for GI infections?
-Anti-pseudo PCN e.g. Piperacillin
- Carbapenems e.g. doripenem, imipenem
- MTZ + FQ’s
- MTZ + ceftriaxone
- MTZ + cefepine
- MTZ = Metronidazole
Empiric AB therapy for urinary tract infections?
Pyelonephritis:
- ceftriaxone
- FQ’s e.g. ciprofloxacin
- Amino PCN e.g. amoxicillin
Acute Cystitis:
- TMP SMX
- Nitroforantoin
- Fosfomycin
- Ciprofloxacin (2nd line)
Complicated UTI:
- Vancomycin
- Amoxicillin/ Ampicillin
- Pipracillin, Cefepine’s
- Gentamycin
Empiric AB therapy for skin/soft tissue infection?
Strep A & MSSA:
PO form: Dicloxacin or Cephalexin
IV form: naficillin or oxacillin or cefezolin
Strep A & MRSA:
PO form: TMP SMX or doxycycline or Clindamycin
IV form: Vancomycin
Empiric AB therapy for bone/joint infections?
- MRSA: Vancomycin
- Neisseria: Ceftriaxone
- Pseudomonas: Cefepine, Ceftazedine
Empiric AB therapy for Sepsis?
-MRSA: vancomycin
-Gram (-) + Anaerobe: Piperacillin or carbapenems
Empiric AB therapy for CNS infection e.g. meningitis?
CAM:
- Vancomycin
- Ceftriaxone (best for CNS penetration)
+/- ampicillin if patient suspected with Listeria
HAM:
- Vancomycin
- Cefepine
Empiric AB therapy for blood stream infections?
- Vancomycin
*if any gram (-) add piperacillin or Tazobactam
Which ABs groups cause Neurotoxicity as an AE?
- PCN
- Cephalosporins
- Carbapenems
- Polymixins
- Linezolid (risk of 5 HT syndrome and peripheral neuropathy)
Which ABs groups cause Nephrotoxicity as an AE?
Indirect Nephrotoxicity:
- PCN
- Cephalosporin
- TMP SMX
Direct Nephrotoxicity:
- AG’s
- Vancomycin
Which ABs groups cause Pancytopenia as an AE?
- PCN
- Cephalosporins
- TMP SMX
- Chloramphenicol
- Linezolid
Which ABs groups cause Respiratory Distress as an AE?
- Polymixins
- Nitroforantoin (causes pulmonary fibrosis)
Which ABs groups cause Myasthenia Gravis worsening as an AE?
- Macrolides
- FQ’s
- AG’s
- Clindamycin
Which ABs groups cause ototoxicity as an AE?
- AG’s
- Vancomycin
Which ABs have teratogenic AE?
- TMP SMX
- FQ’s
- Chloramphenicol
- Doxycycline
Which ABs increase QT interval?
- FQ’s
- Macrolides
Which AB groups cause hemolytic anemia?
(+) Coombs test:
- PCN
- Cephalosporins
Worsen G6PDH Deficiency:
- TMP SMX
- FQ’s
- Nitroforantoin
Which AB groups inhibit CYP450?
- FQ’s
- Macrolides
- TMP SMX
Which ABs cause phototoxicity?
- Doxycycline
- TMP SMX
What are specific AE of PCNs?
- hypersensitivity (IgE)
What are specific AE of Cephalosporins?
- vitamin K decrease therefore risk of bleeding
- Cholecystitis
- Biliary sludge
- In combo with AG’s = increased nephrotoxicity
What are specific AE of Vancomycin?
- phlebitis (when drug is pushed in too quickly)
- red man syndrome: muscle spasm, redness, itchiness
- Drug Related Eosinophilic Systemic Symptoms (DRESS)
What are specific AE of Daptomycin?
- rhabdomyolysis
What are specific AE of Doxycycline?
- Pill induced esophagitis: when not enough water taken with pill or not standing upright when swallowing
- binds to Ca2+ on teeth = teeth staining
What are specific AE of Macrolides?
MACRO
-Motility dysfunction in GI
-Arrhythmia
-Cholestasis
-Rash
-eOsinophilia
What are specific AE of Clindamycin?
- increased risk of C.diff infection
- symptoms e.g. diarrhea
What are specific AE of Linezolid?
- Lactic acidosis
What are specific AE of FQ’s?
- hypo/ hyperglycemia
- destruction of cartilaginous tissue
- tendon rupture, avoid in > 60 years of age
What are specific AE of bactams (TMP SMX)?
- hyperkalemia
Which ABs are most suitable for MSSA?
- FQ’s
- Cephalosporins 1st Gen
- Anti-staph PCN
Which ABs are most suitable for MRSA?
- vancomycin
- 5th gen Cephalosporin
- TMP SMX
- Clindamycin
- Doxycycline
Which ABs are most suitable for Strep. Pneu?
- Penicillin G
- Amino PCN
- Cephalosporin 3rd gen
Which ABs are most suitable for Strep A & B?
- Amino PCN
- Cephalosporin 1st gen
- TMP SMX
- Macrolides
- Clindamycin
Which ABs are most suitable for Enterococcus?
- PCN
- Amino PCN
Which ABs are most suitable for Listeria?
- Amino PCN
- TMP SMX
What are the Gram (+) batceria?
- MSSA
- MRSA
- Enterococcus
- Listeria
- Strep Pneumoniae
- Strep A & B
What does HENS PEcK stand for?
2nd Generation Cephalosporins:
- H. Influenza
- Enterobacteria
- Neisseria Gonorrhoea/ Meningitis
- Serratia
1st Generation Cephalosporins:
- Proteus
- E.coli
- Klebsiella
Which ABs are most suitable for HENS PEcK?
- PEcK: 1st gen Cephalosporins
- HENS: 2nd gen Cephalosporins
- Antipseudo PCN
- Carbapenems
- Monobactams
- FQ’s (but not N)
- AG’s (but not N)
How does bacterial resistance occur?
- AB given without any indication
- AB given for viral infection
- Duration too short or long
- AB not adapted to microbiological finding
- Inadequate dosing
- XS use of broad spectrum ABs
What is the rational approach for AB therapy?
- AB choice
- Dosage
- Duration
- Interactions & SE
- Combination
4D’s:
- right drug
- right dosage
- right duration
- de-escalation
What are the basic principles of rational AB therapy?
- Apply AB with narrowest spectrum of action to the most likely cause of action
- Choose AB with lowest toxicity, price and convenient mode of administration
- Monotherapy, combo justified for better efficacy, broad action, less toxicity and prevention of resistance
- Take a suitable sample before applying ABs
- Bacteriostatic with bactericidal is
contraindicated - Evaluation of therapy 48-72 hrs
How are AB treatment decisions made? What Q’s to ask?
- Once pathogen identified, is there a more narrower spectrum agent that can be used?
- One agent or combo?
- Optimal dose? Route? Duration?
- any susceptibility tests for any patients who don’t respond?
- any adjunctive measures to eradicate infection? e.g. abscess drainage
What is Empirical AB therapy?
- AB are used initially before having identified the specific pathogen causing the infection
- This use of AB is known as Empirical AB Therapy
- the hope of EABT is that early intervention will improve the outcome
What is the 4 step process to Empirical Therapy?
1) Make a clinical Dx of Microbial Infection
2) Obtain specimens for lab exams
3) Formulate microbiological Dx
4) Determine necessary empirical therapy
What factors decide the AB agent choice?
- age
- comorbidities
- pregnancy status
- prior adverse effects
- impaired ability to detoxify or eliminate drug
How may AB therapy be monitored?
Clinically:
- improvement of symptoms e.g. fever, malaise
Microbiologically:
- culture of specimens showing eradication of bacteria
- useful to document reoccurrence or relapse
- follow up cultures to assess for superinfections or resistance
Which ABs are bacteriostatic?
- Macrolides
- Tetracyclines
- Folic Acid Pathway Alters
- Nitroforantoin
Which ABs are bactericidal?
- Daptomycin, Polymixins
- PCN
- Cephalosporins
- Carbapenems
- Monobactam
- AG’s
- FQ’s
- Metronidazole
- Vancomycin
What is the rational approach for combination AB therapy?
- provide broad spectrum empiric therapy for seriously ill patients
- treat polymicrobial infections e.g. abdominal abscess
- decrease emergence of resistant strains
- decrease dose-related toxicity by reducing dose of 1 or more components
- enhance inhibition or killing
What is the AB resistance cycle?
- Increased AB use
- Increase in resistant strain
- Ineffective empiric therapy: increased morbidity and more ABs use
- Increased hospitalisation : more AB use
- increased healthcare resource use
- limited alternatives: more AB use and increased Mortality
How can we reduce bacterial resistance?
- use appropriate sample whenever possible
- monitor and evaluate AB therapy 48-72 hours
- Education about rational use
- Infection prevention and control measures
- AB prescribing control
- Improve microbiological diagnostics
What are the pharmacokinetic changes in severe sepsis?
Phase 1- Lowered drug concentration due to:
- increase CO
- increased clearance extravasation
- increased volume of distribution
- CrCL > 130ml/min
Phase 2- Increased serum drug concentration:
- Organ dysfunction (liver, kidney), therefore decreased clearance
- renal failure
What are some common side effects of ABs in adults?
- nausea
- vomiting
- somnolence
- measles on skin
- arrhythmias
- itchy skin
- hyperkalemia
- site of drug application reaction
What are the drug interactions of FQ’s?
FQ’s susceptible to inhibition of GI absorption
- caffeine
- sucralfate
- theophylline
What are the drug interactions of macrolides
Clarithromycin and erythromycin inhibit CYP3A-4 and P-glycoprotein
- quinidine
- pimozide
- theophylline
What changes are undergone by bacteria when developing resistance?
- enzyme degradation
- target protein changes
- bacterial membrane permeability
- change in ribosome structure
- changes in metabolic pathways
What are URTI and LRTI?
URTI:
- rhinitis
- tonsillopharyngitis
- acute otitis media (AOM)
- acute bacterial rhinosinusitis
LRTI:
- acute bronchitis
- pneumonia
- acute exacerbation of chronic bronchitis
Drug of choice for AOM?
- ABs not always necessary unless infection severe or infection lasts 2-3 days
- amoxicillin
- cephalosporin 2nd or 3rd gen
- Azithromycin
Drug of choice for tonsillopharyngitis?
Children drug of choice:
- PCN V
- Amoxicillin
- 2nd gen cephalosporin
- or clindamycin, macrolides
Drug choice for acute bacterial rhinosinusitis?
- 2nd gen cephalosporins
- amoxicillin
- azithromycin
AB drug choice of acute bronchitis?
- psych you bitch!
- acute bronchitis is predominantly caused by viruses
- AB only if bacterial reinfection
AB drug of choice for exacerbation of chronic bronchitis?
First line:
- Amoxicillin
- 2nd or 3rd gen cephalosporins
alternatives: azithromycin or doxycycline
*considering causes and resistance to beta-lactamase ABs- cefuroxime can be used
What classes of ABs are there? Give examples.
*ABs Can Protect The Queens Men, Servants & Guards
- AG’s e.g. Gentamycin
- Cephalsporins e.g. ceftriaxone
- PCN’s e.g. PCN G or amoxicillin
- Tetracycline e.g. doxycycline
- Quinolones/ FQ’s e.g. ciprofloxacin
- Macrolides e.g. erythromycin
- Sulfonamides e.g. sulfamethoxazole
- Glycopeptides e.g. Vancomycin
