Cell wall synthesis inhibitors/membrane active antibiotics (1&8&9&10&/17/&19) Flashcards
Cell Wall Synthesis Inhibitors & Membrane-Active Antibiotics
Penicillins Cephalosporins Carbapenems. Monobactams. Beta-lactamase inhibitors.
Pharmacotherapy of respiratory infections
Community aquired pneumonia
typical pneumonia: acute fever, chills productive cough pleural pain physical signs (+) lobar consolidation
agents: S. pneumoniae H. influenzae Gr(-)aerop. bacillus anaerobes (Klebsiella pneumoniae Peptostreptococcus, Bacteroides, Fusobacterium, and Prevotella)
atypical pneumonia: subacute subfebrile fever non productive cough nonrespiratory symtopms physical signs (-) non-lobar infiltration
Agents: M. pneumonia C. pneumoniae L. pneumophila virus
types of antibiotic therapy
- emperic
- sensitivity based (definitive)
- prophylactic
Considerations in choice of antimicrobial agent
- antibacterial spectrum
- site of infection
- pharmacokinetics of the antimicrobial agents
- adverse effects
- presence of renal or hepatic failure
- drug interaction
- severity of infection
- general condition of the patient (concomitant disease, state of immune system, age, pregnancy)
- cost
MIC
Minimum Inhibitory Concentration is the lowest drug concentration that prevents visible microorganism growth after overnight incubation
A lower MIC - more effective antimicrobial agents
MBC
The minimum bactericidal concentration (MBC) is the lowest concentration of an antibacterial agent required to kill a particular bacterium
Bactericidal
An antimicrobial drug that can eradicate an infection in the absence of
host defense mechanisms; kills bacteria
Bacteriostatic
An antimicrobial drug that inhibits antimicrobial growth but requires host defense mechanisms to eradicate the infection; does not kill bacteria
osteomyelitis
S. aureus, group A strep. (pyrogens)
septic arthritis
S. aureus, N. gonorrheae (if sexually active), streptococci
cellulitis
beta-hemolytic strep., S. aureus
bactericidal antibiotics
beta-lactams* glycopeptides* aminoglycosides quinolones/fluoroquinolones metronidazol rifampin isoniazid
Bactericidal agents has be given in case of endocarditis, meningitis or infections in immunocompromised patients
- Inhibit but not kill enterococci
ß GAFRIM
bacteriostatic
chloramphenicol lincosamides macrolides tetracyclines sulfonamides trimethoprim nitrofurantoin ethambutol
CHESTT NLM
postantibiotic effect
The post antibiotic effect (PAE) is defined as persistent suppression of bacterial growth after a brief exposure (1 or 2 hours) of bacteria to an antibiotic
perioperative antiobiotic
metronidazole - abdominal surgery?!
Cephalosporin???3rd- surgical prophylaxis
Cefazolin??
Combination of antimicrobial agents
Aim 1. To assure a synergistic effect penicillins + aminoglycosides sulfonamides + trimethoprim 2. To extend the antibacterial spectrum 3. To prevent the development of resistance
e.g. . Ps. Aeruginosa, acinetobacter infection
antimycobacterial agents
Indications for prophylactic treatment
- surgical prophylaxis - cephalosporins
non- surgical prophylaxis
- individuals with high risk e.g. immunocompromised patients, patients with endocarditis
- recurrent infections e.g. urinary, genital herpes, otitis media
- close contacts e.g. meningococcal infection, tuberculosis, pertussis, plague etc.
- risk of infection (endemic area) e.g. malaria, anthrax
N. meningitis, TB, yersenia pestis
dentoalveolar surgeires
abdominal surgeries (perioperative antibiotics)
Narrow spectrum,
G-penicilline, vancomycine, oxazolidine, (linezolid) lincosamide, fuzidic acid (use slide)
P-VOLF
Extended spectrum
aminoglycosides, aminopenicillines, 2nd and 3rd generation cephalosporins, some fluoroquinolones, macrolides (use slide)
CAFAM
Broad spectrum
tetracyclines, carbapenems, 4th generation fluoroquinolones, chloramphenicol, piperacilline+tazobactam (use slide)
FC TCP
Which tissues are hard to penetrate?
°CNS • Prostate • bones • endocarditis vegetation • Ischemic tissues • implants • Intracellular pathogens
Bacterial cell wal synthesis inhibitors
- Beta lactams
1.1. Penicillins
1.2. Cephalosporins
1.3. Carbapenems
1.4. Monobactams- Aztreonam
(ß-lactamase inhibitors) - Glycopeptides: Vancomycin, Teicoplanin
- Bacitracin
- Fosfomycin
2.,3.,4., also inhibit cell wall synthesis but are not nearly as important as the beta-lactam drugs
Beta-lactams mechanism of action
which pathogens are resistant by nature
1) binding of the drug to specific enzymes - penicillin-binding proteins (transpeptidation)
- 2) inhibition of the FINAL transpeptidation reaction that cross-links the linear peptidoglycan chain
- 3) activation of autolytic enzymes that cause lesions in the bacterial cell wall
• b-lactams are ineffective against :
– bacteria without cell wall (mycoplasma, ureaplasma)
– obligate intracellular parasites (chlamydia, rickettsia, legionella)
– facultative intracellular parasites (may have some effect) (e.g. brucella, salmonella)
– slowly growing bacteria (e.g. mycobacteria)
Beta-lactams - Resistance
- b-lactamase production–MAJOR MECHANISM!!!
• by most staphylococci and many gram-negative organisms
• Inhibitors of these bacterial enzymes (eg, clavulanic acid, sulbactam, tazobactam) prevent their inactivation - altered PBP (penicilin-binding-protein?)
• responsible for methicillin resistance in staphylococci and for resistance to penicillin G in pneumococci (penicillin resistant Streptococcus pneumoniae (PRSP)) and enterococci. - impaired penetration
- efflux
special considerations of Beta-lactams (resistance by nature)
- No intracellular penetration
– chlamydia, rickettsia, legionella (intrac. bacteria)
http://what-when-how.com/medical-microbiology-and-infection/chlamydia- mycoplasma-and-rickettsia-bacteriology-medical-microbiology-and-infection/
- No effect on bacteria without cell walls
– mycoplasm, ureaplasm - No effect on slow-growing bacteria
– Mycobacteria - Side effects:
– allergy
– seizures
PENICILLINS
Pharmacokinetics:
• oral and/or parenteral use
• short half life (0,5 – 1,5 h) + short PostAE → dosage 3-4 times daily
• Nafcillin is excreted mainly in the bile and ampicillin undergoes enterohepatic cycling
• Good anaerobic spectrum
• extracellular distribution (no effect against intracellular pathogens)
• poor penetration into the eye, prostate, bones and CNS
– in case of meningitis better penetration, but decreases by
therapeutic success
• penicillins cross the placenta and enter the breast milk
• ~ 30 % metabolized in the liver
• ~ 70 % excreted by the kidneys (20 % filtration, 80 % tubular secretion)
– dose reduction in kidney failure
side effects:
• safe during pregnancy
- allergy (most common adverse effect, ~ 1 %)
– skin rash, urticaria, pruritus, fever
– anaphylacticshock(~0,05%)
– pseudoallergic morbilliform rash by aminopenicillins - Ampicillin!!!
• cross allergy between penicillins (in 5 % also with cephalosporins) + Complete crossallergenicity between different penicillins should be assumed
°maculopapular rash (ampicillin) - gastrointestinal (more frequent with oral agents) nausea, diarrhea - direct irritation or by overgrowth of gram-positive organisms or yeasts
- dysbacteriosis, pseudomembranous colitis C.difficile,rare) • Th.: metronidazole, vancomycin - hematologic
– anemia,thrombocytopenia,neutropenia - irritation and local pain (if given i.m.)
- neurotoxicity (seizures, at higher doses, esp. in case of kidney failure)
classifications:
°Penicillin G and close derivatives
– Penicillin G (Benzylpenicillin), depot forms, oral forms
• b-lactamase stable penicillins
• Extended-spectrum penicillins (aminopenicillins)
• Antipseudomonal penicillins
• Combination with b-Lactamase inhibitors
• Narrow-spectrum penicillinase-susceptible agents
penase-susceptible:
– Penicillin G is the prototype (acid sensitive)
– Penicillin V is an oral drug used mainly in oropharyngeal infections. (acid-resistant)
-(streptococcal, meningococcal infections, syphilis)
-rapid renal elimination (frequent dosing)
• Very-narrow-spectrum penicillinase-resistant drugs
(penase-resistant)
– methicillin (the prototype, rarely used owing to its nephrotoxic potential),
nafcillin, oxacillin
– Their primary use in staphylococcal infections
- some biliary clearance (recycling)
– Methicillinresistant (MR) staphylococci
• Wider-spectrum (extended) penicillinase-susceptible drugs
-greater activity against gram negative bacteria
-bactericidal
– Ampicillin and amoxicillin (penase-sensitive, but wider spectrum)
• Their clinical uses include indications similar to penicillin G
• + infections resulting from enterococci, Listeria monocytogenes, Escherichia coli, Proteus mirabilis, Haemophilus influenzae, and Moraxella catarrhalis,
• When used in combination with inhibitors of penicillinases (eg, clavulanic acid), their antibacterial activity is often enhanced
Broad spectrum
– Piperacillin and ticarcillin
• gram-negative rods, including Pseudomonas, Enterobacter, and in some cases Klebsiella
species.
• Most drugs in this subgroup have synergistic actions when used with aminoglycosides against such organisms.
• Piperacillin and ticarcillin are susceptible to penicillinases and are often used in combination with penicillinase inhibitors (eg, tazobactam and clavulanic acid) to enhance their activity.
amoxicillin - clavulanic acid
ampicillin - sulbactam
