Inhibitors of Bacterial Cell Wall Synthesis Flashcards
Gram-negative membrane
Lipid A portion of lipopolysaccharide - endotoxin responsible for gram-negative sepsis
Cell wall protects the bacteria from
Osmotic lysis if it is placed in a hypotonic solution
Antibiotics secreted in bile
Nafcillin
Ampicillin
Ceftriaxone
Two forms of long-acting penicillin G and their administration
Procaine penicillin G and Benzathine penicillin G
Intramuscular administration
Benzathine penicillin G plasma concentration
Low plasma concentration of the drug for a few weeks
Procaine penicillin G plasma concentration
Higher plasma concentrations of penicillin for about 24 hours
Extended spectrum Carboxypenicillins
Carbenicillin
Ticarcillin
Extended spectrum Ureidopenicillins
Piperacillin
Mezlocillin
Azlocillin
Extended spectrum Aminopenicillins
Ampicillin
Amoxicillin
Extended spectrum Ureidopenicillins active against
Selected gram-negative bacilli, such as Klebsiella pneumoniae
Penicillinase-Resistant Antistaphylococcal Penicillins
Methicillin Nafcillin Oxacillin (Isoxazolyl penicillin) Cloxacillin (Isoxazolyl penicillin) Dicloxacillin (Isoxazolyl penicillin)
Narrow-Spectrum Penicillins
Penicillin G
Penicillin V
First-generation cephalosporins
Cefazolin
Cephalexin
Second-generation cephalosporins
Cefuroxime
Cefprozil
Cefoxitin
Cefotetan
Third-generation cephalosporins
Cefotaxime
Ceftazidime
Ceftriaxone
Cefpodoxime
First-generation cephalosporins active against
Gram-positive cocci, such as pneumococci, streptococci, and staphylococci. They are also active against a few gram-negative enteric bacilli including E. coli and K. pneumoniae
Second-generation cephalosporins active against
Similar activity against gram-positive cocci as the first-generation while demonstrating increased activity against gram-negative bacilli
Third-generation cephalosporins active against
Wider range of gram-negative organisms including enteric gram-negative bacilli (Enterobacteriaceae), H. influenzae, and M. catarrhalis
Which bacteria have acquired plasmin-mediated TEM and SHV b-lactamases?
Many strains of Enterobacteriaceae, including Escherichia Coli and Klebsiella pneumoniae
Avibactam
b-lactamase inhibitor with a unique non-b-lactame structure
Avibactam active against
Several types of b-lactamases, including AmpC b-lactamases and other extended-spectrum b-lactamases expressed by cephalosporin-resistant gram-negative bacteria
Fourth and Advanced (fifth)-generation cephalosporin
Cefepime
Ceftaroline
Fourth-generation cephalosporin active against
P aeruginosa, Enterobacteriaceae, S aureus, and S pneumoniae. It is highly active against Haemophilus and Neisseria sp.
Carbapenem with high affinity for PBP-2
Imipenem
Carbapenem that binds both PBP-2 and PBP-3
Meropenem
Penicillin G - Clinical use
Gram-positive cocci Syphilis-Treponema pallidum Endocarditis- Viridans, streptococci, enterococci Meningitis - Meningococci Pneumonia -Pneumococci Streptococci Enterococci Gas gangrene – Clostridium perfringes Actinomyces
Penicillin G+V, Dicloxacillin, Nafcillin, Methicillin, Piperacillin, Ticarcillin - Adverse effects
High dose: seizures Diarrhea Superinfections Psuedomembranous colitis Hypersensitivity: Uritcaria (hives) Anaphylactic shock Serum sickness Interstitial nephritis Hepatitis Rashes
Penicillin G - Interactions
Probenecid: inhibits renal secretion – increased serum concentration
Benzathine: prolonged half-life.
Penicillin V - Clinical use
Gram-positive cocci
Pharyngitis – Streptococcus pyogenes
Dicloxacillin and Nafcillin - Clinical use
Milder infections of penicillinase positive staphylococci Osteomyelitis Endocarditis Pneumonia Skin and soft tissue infections
Nafcillin - Special considerations
IV adm for serious infections
Excreted in bile
Nafcillin - Interactions
Probenecid: inhibits renal secretion – increased serum concentration
Metchicillin - Clinical use
Seldom used because of resistance and adverse effects
Metchicillin - Special considerations
Original drug in this pharm class. Resistance by MRSA
Amoxicillin - Clinical use
Otitis media Upper respiratory tract infections Skin and soft tissue infections UTI’s Sinusitis Bronchitis Community acquired pneumonia
Prophylaxis of bacterial endocarditis in persons with heart valve defects
Pneumococci, streptococci, staphylococci, Haemophilus influenzae, Moraxella catarrhalis, Escherichia coli, Pasteurella multocida
Bite wound infections – Pasteurella multocida, S. aureus(with clavulanate)
Impetigo (with clavulanate) - S. aureus, S. pyogenes
Amoxicillin - Special considerations
Bec of resistance: use clavulanate for H. influenzae + M. catarrhalis.
Uptake is not impaired by food, unlike the other penicillins
Amoxicillin - Adverse effects
High dose: seizures Diarrhea Superinfections Psuedomembranous colitis Hypersensitivity: Uritcaria (hives) Anaphylactic shock Serum sickness Interstitial nephritis Hepatitis Rashes
Amoxicillin - Interactions
Clavulanate: β-lactamase inhibitor
Probenecid: inhibits renal secretion – increased serum concentration
Contraceptive: Decreased effectiveness
Amoxicillin - Similar drugs
Ampicillin
Piperacillin
Ticarcillin
Ampicillin - Clinical use
Meningitis, listeriosis – Listeria monocytogenes
Decubitus, diabetic foot ulcers – Gram-positive and anaerobic organisms
Endocarditis – Streptococci, enterococci
Lyme disease – Borrelia burgdorferi
Shigellosis
Uncomplicated salmonella
Gastroenteritis E.coli
Non b-lactamase producing strains of H. influenzae
Bite wounds and diabetic foot ulcers (with sulbactam)
Combined with aminoglycoside (E.g., gentamicin) to treat enterococcal infections, such as enterococcal endocarditis
Ampicillin - Adverse effects
Maculopapular rash (viral inf. Like mononucleosis) High dose: seizures Diarrhea Superinfections Psuedomembranous colitis Vaginal candidiasis Hypersensitivity: Uritcaria (hives) Anaphylactic shock Serum sickness Interstitial nephritis Hepatitis Rashes
Ampicillin - Interactions
Sulbactam: β-lactamase inhibitor
Piperacillin, Ticarcillin - Clinical use
Gram-positive and gram-negative aerobic and anaerobic bacteria + some strains of Pseudomonas aeruginosa and Klebsiella pneumonia
Intraabdominal, skin, soft tissue, lower respiratory tract, complicated urinary tract, gynecologic
Febrile neutropenia
pneumonia.
Active against P.aeruginosa (UTIs)
Piperacillin Ticarcillin - Interactions
Tazobactam: β-lactamase inhibitor Aminoglycosides Probenecid: inhibits renal secretion – increased serum concentration Contraceptivse: Decreased effectiveness Clavulanate: β-lactamase inhibitor Aminoglycoside
Cephalexin - Clinical use
Skin and soft tissue infections (impetigo, cellulitis) caused by gram (+)
UTIs -Streptococci, staphylococci
Cephalosporins - Adverse effects
Hypersensitivity: (rare, cross-sensitivity to penicillins)
Anaphylaxis, fever, skin rashes, nephritis, granulocytopenia, hemolytic anemia
Local irritation: pain after IM injection, thrombophlebitis after IV
Renal toxicity (intersitial nephritis, tubular necrosis)
Cefotetan: + Platelet dysfunction and bleeding
Cefepime: + Drug-induced encephalopathy
Cefazolin - Clinical use
Prophylaxis of surgical infections – Staphylococci, E. coli, K. pneumoniae
Alternative to antistaph. penicillin
Cefprozil, Cefuroxime - Clinical use
Otitis media – H. influenzae strains resistant to amoxicillin and other drugs
Respiratory tract, skin and soft tissue infections (pneumococci, H. influenzae, M. catarrhalis)
Cefotetan - Clinical use
Aerobic and anaerobic gram-negative bacilli, including Bacteroides fragilis
Intra-abdominal, gynecological, biliary tract infections
Cefotetan - Interactions
Anticoagulants: more potent effect (risk of bleeding!)
Alcohol: disulfiram-like reaction
Cefoxitin - Clinical use
Surgical prophylaxis for gram-neg
Ceftazidime - Clinical use
AVYCAZ: ceftazidime + avibactam
Intraabdominal infections
UTIs
Pneumonia
P. aeruginosa and other gram-negative bacteria
Ceftazidime - Special considerations
Resistant to some Class-C β-lactamases such as Amp C cephalosporins, TEM, SHV
Cefpodoxime, Cefotaxime - Clinical use
Gonorrhea
Ceftriaxone - Clinical use
Gonorrhea, UTIs, otitis, meningitis, pneumonia, Lyme disease – Gonococci, pneumococci, meningococci, B. burgdorferi, H. influenzae
Cefepime - Clinical use
Intraabdmonial infections
UTIs
Pneumonia
Skin and soft tissue infections
Drug-resistant gram-negative bacilli, including Citrobacter and Enterobacter species
Ceftaroline - Clinical use
Community-acquired pneumonia
Skin and soft tissue infections
MRSA, Drug resistant pneumococci
Aztreonam - Pharmacologic class + Clinical use
Monobactam
Aerobic gram-negative bacilli
Enterobacter, Citrobacter, Klebsiella, Proteus, P. aeruginosa
UTIs, gynecological, intra-abdominal, skin, lung infections
Pneumonia
Meningitis
Sepsis
Azetreonam - Special considerations
Cross-sensitivity for penicillin is not common
Resistant to most beta-lactamses
Azetreonam - Adverse effects
Hypersensitivity reactions
Thrombophlebitis
Skin rashes
Increases level of serum aminotransferase
Carbapenems - Clinical use
Active against gram (-) rods- P. Aeruginosa, and gram (+) org.
Endocarditis
Pneumonia
UTIs
Pelvic, skin, soft tissue, intra-abdominal inf.
Meningitis, febrile neutropenia,
sepsis
Imipenem - Special considerations + Contraindications
Resistant to most b-lactamases but not carbapenemase of metallo b-lactamase.
Excessive levels of imipenem in patients with renal failure may lead to seizures
Carbapenems - Adverse effects
Cross-sensitivity with penicillin allergy Seizures in patients with epilepsy and renal failure Diarrhea Vomiting Anemia Leukopenia Thrombocytopenia Altered bleeding time
Imipenem - Interactions
Cilastatin: dehydropeptidase inhibitor that increases time of activity of imipenem.
Vancomycin - Clinical use
Gram-positive cocci and bacilli, MRSA
Streptococcal and enterococcal infections caused by penicillin-resistant organisms, including endocarditis and necrotizing fasciitis
Meningitis caused by penicillin-resistant strain of pneumococcus (in combination with cefotaxime, ceftriaxone, or rifampin)
Bacillus, Clostridium, Cornyebacterium species
Bone and joint, skin and soft tissue infections
Pneumonia
Septicemia
Endocarditis
Vancomycin, Telavancin - Adverse effects
Reduced nephro- and ototoxicity now compared to before
Hypotension and erythematous rash with to quick infusion (called red man syndrome)
Vestibular dysfunction (ataxia, vertigo, nystagmus, nausea)
Cochlear dysfunction (tinnitus, hearing loss)
Irritating to tissue phlebitis at site of injection
Chills, fever
Vancomycin - Interactions
Aminoglycosides and amphothericin B: Increased nephrotoxicity
Telavancin - Clinical use
Skin and soft tissue inf by MSSA+ MRSA + vancomycin-sensitive E. faecalis
Telavancin - Contraindications
Do not administer to pregnant women, it is teratogenic
Bacitracin - Clinical use
Gram-positive cocci, including staphylococci and streptococci
Skin and eye infections
Combined with polymyxin and neomycin
Bacitracin - Special considerations
Used only for topical treatment
Bacitracin - Adverse effects
Very nephrotoxic
Fosfomycin - Clinical use
Enterococci and many gram-negative enteric bacilli, including E. coli, Citrobacter, Klebsiella, Proteus, Serratia marcescens
Uncomplicated UTIs by E. coli or E. faecalis
Fosfomycin - Adverse effects
Diarrhea
Beta lactam antibiotics (Penicillins, cephalosporins, monobactam, carbapenems) - MoA
Binds to PBPs, inhibiting cross-linking of peptidoglycan -> inhibition of bacterial cell wall synthesis.
Bacitracin - MoA
Inhibition of regeneration of bactoprenol phosphate (C55-isoprenyl P)
Fosfomycin - MoA
Inhibiton of enolpyruvyl transferase, blocks the addition of phosphoenolpyruvate to UDP-GlcNAc, prevents synthesis of UDP-MurNAc
–> Blocks synthesis of peptidoglycan
Vancomycin - MoA
Binds to peptidoglycan and prevents cross lining–> inhibits cell wall synthesis
