Antibiotics Flashcards
What class of antibiotics does Clindamycin belong to?
Lincosamide (related to macrolide)
Clindamycin is related to the macrolide class of antibiotics.
What is the primary mechanism of action of Clindamycin?
Protein synthesis inhibitor
Clindamycin is known to limit exotoxin production.
How does Clindamycin affect outcomes in Toxic Shock caused by Strep pyogenes?
Improves outcomes
Clindamycin is effective in managing Toxic Shock related to Strep pyogenes.
Is Clindamycin well absorbed in the body?
Yes
Clindamycin is a good option for skin and soft tissue infections if the bacteria are susceptible.
In which pediatric conditions is Clindamycin increasingly supported for effectiveness?
- Pneumonia
- Empyema
- Bone/joint MRSA infections
Literature supports Clindamycin’s use in these pediatric infections.
What type of resistance is associated with Clindamycin?
Resistance mediated by the same gene as erythromycin
This resistance occurs via target site modification of the ribosomal binding site.
What risk is associated with erythromycin-resistant bacteria?
Inducible clindamycin resistance
If a bacteria is erythromycin-resistant, there is a risk of developing inducible resistance to clindamycin.
Fill in the blank: Clindamycin is known to limit _______ production.
exotoxin
Clindamycin’s inhibition of exotoxin production helps in treating certain infections.
True or False: Clindamycin is ineffective against severe S. aureus infections.
False
Clindamycin has a similar effect in severe S. aureus infections.
What types of infections is Doxycycline not recommended for?
Complicated or serious infections
Doxycycline should not be used for endovascular infections.
What are the common side effects of Doxycycline?
- Photosensitivity
- Oesophageal irritation
- Enamel stain
Enamel staining is more pronounced when comparing tetracycline to doxycycline.
Beta-lactam antibiotics
Penicillins, Cephalosporins, Carbapenems, Monobactams
Mechanism of action of beta lactam antibiotics
Interfere with cell wall synthesis
Glycopeptide antibiotic
Vancomycin
Mechanism of action of Vancomycin
Interfere with cell wall synthesis, binds to D-Alanyl-D-Alanine and prevents cross linking
Antibiotics that interfere with nucleic acid synthesis
Sulfonamides, Trimethoprim, Quinolones, Rifampicin
Antibiotics target folate synthesis
Sulfonamides, Trimethoprim
Antibiotics target DNA gyrase
QuinolonesA
Antibiotic target RNA polymerase
Rifampicin
Antibiotics targeting protein synthesis
Tetracylines, Aminoglycosides, Macrolides, Clindamycin, Linezolid, Chloramphenicol
Antibiotics targeting 30s subunit ribosome
Tetracylines, aminoglycosides
Antibiotics targeting 50s subunit ribosome
Macrolides, Clindamycin, Linezolid, Chloramphenicol
Antibiotics that depend on CMax
Aminoglycosides, fluoroquinolones
Antibiotics that depend on AUC/MIC
Vancomycin, Azithromycin, Fluoroquinolones, Aminoglycosides, LinezolidA
Antibiotics that depend on T >MIC (dosing interval)
Beta lactams, Clindamycin, Vancomycin, Macrolides
Antibiotics with >90% bioavailability
Clindamycin, Doxycycline, Linezolid, Metronidazole, Rifampin, Fluconazole, Voriconazole
Antibiotics with 80- 90% bioavailability
Amoxicillin, Cephalexin, Ciprofloxacin, Cotrimoxazole
Antibiotics with 60 - 80% bioavailability
Penicillin VK, Valganciclovir
Antibiotics with <60% bioavailability
Cefuroxime, Augmentin, Azithromycin, Aciclovir, Fosfomycin, Clarithromycin
Antibiotics with low oral bioavailability due to low intestinal permeability
Amikacin, Gentamicin, Ceftazadime, Vancomycin
Beta lactam antibiotic side effects
Hypersensitivity, neurotoxicity and reduced seizure threshold at higher doses, GI upset, LFT derangement
Glycopeptide side effects (Vancomycin)
Red Man Syndrome (fast infusion rate), nephrotoxicity
Aminoglycoside side effects
Ototoxicity, nephrotoxicity
Macrolide side effects
QTc prolongation, CYP3A4 enzyme inhibition
Fluoroquinolone side effects e.g. Ciprofloxacin
Tendinopathy, neurotoxicity and seizure threshold, QTC prolongation
Tetracycline side effects
Enamel staining, oesophageal irritation, photosensitivity
Antifolate (Cotrim)
Rash (including SJS), Cytopenia
Chloramphenicol side effect
Grey baby syndrme, aplastic anaemia
Clindamycin s/e
GI upset, rash
Metronidazole s/e
Peripheral neuropathy
Nitrofurantoin s/e
Peripheral neuropathy, hepatotoxic (long term), pulmonary fibrosis (long term), haemolytic anaemia in neonates
Daptomycin s/e
Myopathy, Rhabdomyolysis, Eosinophillic Pneumonia
Antbiotics that disrupt bacterial cell membrane
Daptomycin, Polymixin B
Penicillin mechanism of action
Bind to PBPs and inhibit completion of peptidoglycans and bacteral cell wall lysis
Penicillinase resistant penicillins
Methicillin, Flucloxacillin (treat staph + strep, don’t treat enterococci)
Aminopenicillins
Amoxicillin (has amino group that give it some gram negative cover)
Natural penicillins
Penicillin G (Strep, Enterococci, Listeria, Neisseria, Syphillis)
Acyl Ureidopenicillins
Piperacillin (extended gram negative cover, including Pseudomonas)
Beta lactam/Beta lactamase inhibitor antibiotics (overcome acquired resistance mechanism of enzymatic modification)
Augmentin (Amox/Clavulanic Acid) and Tazocin (Piperacillin/Tazobactam)
Benefit of beta-lactam/beta lactamase inhibitor antibiotics
Better activity against gram negative bacilli, MSSA, Beta-lactam producing anaerobes. Tazoscin is also antipseudomonal
Cephalosporins mechanism of action
Same as penicillins (bind to PBPs, but differing affinity) and cause cell wall lysis. NO activity against enterococci and reduced activity against listeria. Resistant to beta lactamases produced by Staph Aureus
1st generation Cephalosporins
Cephazolin, Cephalexin (MSSA, Strep cover)
2nd generation Cephalosporins
Cefuroxime, Cefaclor (better Gram negative, specifically against H. Influenzae)
3rd generation Cephalosporins
Ceftriaxone, Cefotaxime, Ceftazadime (good gram negative and broad spectrum gram positive), good CNS penetration
What bacteria enzymes inactivate 3rd generation cephalosporins
ESBL and AmpC
Why can Ceftriaxone be once daily dosed?
Highly protein bound
Which 3rd generation cephalosporin has anti-pseudomonal activity?
Ceftazadime
4th generation cephalosporins
Cefepime, Ceftaroline
Cefepime coverage
Antipseudomonal, AmpC resistant
Ceftaroline coverage
Anti MRSA and resistant pnuemonocci, able to bind to PBP2a
Carbapenem antibiotics
Meropenem, Ertapenem, Imipenem
Carbapenem coverage
Gram positive, Gram negative including ESBL+, Pseudomonas (except Ertapenem). Not MRSA or VREi
Side effect of Carbapenem
Neurotoxicity, lowers seizure threshold (especially Imipenem)
Types of antibiotic resistance
Intrinsic, Acquired and Adaptive/Inducible
Example of intrinsic antibiotic resistance
Vancomycin and Penicillins don’t work for Gram negatives as cannot penetrate LPS layer, Cephalosporins don’t work for Enterococci due to low affinity for enterococcal PBP
Example of acquired antibiotic resistance
Usually chromosome or plasmid mediated (MRSA = Chromosome, ESBL = Plasmid)
Example of adaptive/inducible resistance
Upregulates in presence of stressors e.g. ESCAPM versus beta lactams, Pseudomonas efflux pumps or porin channels versus everything
Four main mechanisms of antibiotic resistance
Enzymatic inactivation of antibiotic e.g. beta-lactamase
Alteration of antimicrobial binding side
Active efflux
Alterations in membrane permeability
Choice of antibiotic for enterococcus faecalis
Penicillin or Amoxicillin
Choice of antibiotic for Enterococcus faecium
Vancomycin
Streptococcus Pneumoniae resistance mechanism
Decreased affinity of PBP. Enzyme gene alteration, leading to decreased affinity of penicillin to penicillin binding proteins (2b alterations give low level resistance, 2x alterations give high level resistance)
Streptococcus Pneumoniae choice of antibiotic
Penicillin (provided not meningitis), aiming MIC ) of 0.06 to 2
Cephalosporin (Ceftriaxone, Cefotaxime) if meningitis for CNS penetration, wouldn’t rationalise to Penicillin unless MIC <0.06. Vancomycin added as potential for altered PBPs within pneumococcus
Strep Pneumoniae treatment if resistant to cephalosporins and penicillins
Vancomycin, add Rifampicin. Consider Linezolid or Moxifloxacin
Haemophillus Influenzae mechanism of antibiotic resistance
Enzymatic deactivation (beta-lactamase positive e.g. Amox resistant and Augmentin susceptible)
Alteration of PBP (BLNAR- beta lactamase negative antibiotic resistance, treat with Cephalosporin or Cotrimoxazole)
Staphyloccous Aureus resistance mechanisms
90% produce enzyme (beta-lactamase/penicillinase) that inactivates penicillins
How do anti-staph penicillins work
Different side chain which reduces access of b-lactamase enzyme
Flucloxacillin adverse effects
Allergy, Bone marrow suppression at thigh doses, hepatotoxicity (including cholestatic liver failure), interstitial nephritis
What disease states is Vancomycin best for and why?
Hydrophillic drug therefore good for bacteraemia and endocarditis but poor tissue penetration
MRSA mechanisms of antibiotic resistance
Altered receptor binding or replacement of target site. Altered PBP2a (acquired genetic element unlike intrinsic set PBP1-4), which is encoded by the mec gene therefore penicillin can’t bind. Lab can test for mecA gene by PCR s rapid MRSA diagnostics
Antibiotics which MRSA is resistant to
All penicillins and cephalosporins
MRSA therapy options
Clindamycin, Vancomycin, Cotrimoxazole, Erythromycin Doxycline, (Gentamicin, Rifampicin, Fusidic Acid). Linezolid, Daptomycin, Ceftaroline
What is the D zone test?
Inducible macrolide-lacosamide resistance. Modification of target RRNA of Staph Aureus on ERM gene. Erythromycin are strongest inducers of these gene but lincosamides are also weak inducers. Therefore if S.Aureus resistance to erythromycin on this test, there is a risk of inducible clindamycin resistance
What type of infection should Co-trimoxazole not be used for?
Endovascular
What does Co-trimoxazole cover?
MRSA, Gram positives and negatives, unusual infections (PJP, Toxoplasma, Stenotrophomonas)
Linezolid class of antibiotic
Oxazolidinone
Linezolid coverage
Gram positive action including MRSA and penicillin resistant S. Pnuemoniae, For serious VRE and MRSA organisms
Linezolid mechanism of action
Targets protein synthesis at early stage (?alternative to Clindamycin for STSS)
Side effects of Linezolid
Optic neuritis and peripheral neuropathy with >4 weeks therapy, thrombocytopenia
Anti-toxin production options in STSS
Clindamycin, Linezolid, IVIg
Gram negative organism mechanisms of resistance
ESBLs and AMPc
What antibiotic are ESBL organisms sensitive and resistant to?
Sensitive: Carbapenems +/- Amikacin. Nitrofurantoin for lower UTI, Fosfomycin
Resistant: Penicillins, Cephalosporins, Monobactam
Risk factors for ESBL organism
Travel, prolonged hospitalisation, multiple courses of antibiotics, indwelling catheters, malignancy, GI tract disease
What organisms are ESBL found on
E. Coli, Klebsiella Pneumoniae, Klebsiella Oxytoca
What is AMPc
Cephalosporinase, inducible resistance to penicillins, cephalosporins and gram negative acting penicillins (Tazoscin)
What organisms produced AMPc
ESCAPM organisms. Enterobacter species, Citrobacter freundii, Serratia Marcescens, Proteus species, Providencia species, Morganella morganii
Oral antibiotics are non-inferior in
BJI without bacteremia, pneumonia, SSTI
MERINO trial finding
Tazoscin is not as effective as Meropenem for treatment of ESBL gram negative organisms