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β-lactam antibiotics, Mechanism of Bacterial Resistance, / - Coggle…

- - - - (probenecid
        competes for secretion will increased plasma penicillin levels).
  - - - e.g. Methicillin (prototype), nafcillin, oxacillin
        dicloxacillin
      - Spectrum
        
        same as Penicillin G but less potent
        
        Minimal activity against gram (-) infections
    - - Aminopenicillins
        
        e.g. Ampicillin (PO/IV), Amoxicillin (PO)
        
        Spectrum
        
        Same as Penicillin G and have improved activity against gram (-) but less potion
        
        With β-lactamase inhibitor
        
        Amoxicillin/clavulanate (PO)
      - Antipseudomonal penicillins
        
        e.g. Carbenicillin, Ticarcillin, Piperacellin (parentral)
        
        Spectrum
        
        .
        
        Same as Aminopenicillins plus activity against
        
        ex. Pseudomonas, Proteus & Klebsiella
        
        (requires clavulanic acid or tazobactam)
    - - sensitive to destruction by β-lactamases
        
        has two types
        
        Penicillin G
        
        Active against gram (+/-) cocci & gram (+) bacilli
        
        (non-β-lactamase producing
        
        Parenteral (IV or IM)
        
        (IM) sustained release
        
        Penicillin V
        
        In gonorrhea & meningococcal meningitis
        
        Same as Penicillin G but less potent
- - - - therefore
        
        have a broader spectrum of activity.
  - - - e.g. Cefuroxime,Cefoxitin,
      - Spectrum
        
        Used primarily in management of URTI, urinary tract, bone & soft-tissue infections
        
        Perioperative surgical prophylaxis
        
        Do not penetrate CSF
        
        less potent against gram (+)
        Better activity against gram (-)
    - - e.g. Cefotaxime, Ceftriaxone, Cefdinir, Cefixime
      - Spectrum
        
        Less potent than the first generation against gram (+)
        organisms but much more effective against gram (-)
        
        do inhibit Pseudomonas
        
        Most penetrate CSF to achieve therapeutically active
        concentrations.
        
        Used for hospital-acquired gram (-), lower respiratory tract infections, urinary tract infection (UTI), meningitis, lyme disease
    - - e.g. Cefepime
      - Spectrum
        
        stable to hydrolysis by many β-lactamases that
        inactivate many of the third generation cephalosporins
        
        good activity against Pseudomonas . highly active against haemophilus and neisseria
        
        excellent penetration into the CSF
    - - e.g. Ceftaroline
      - Spectrum
        
        Excellent activity against streptococci, MSSA, MRSA
        
        Used in treatment of complicated skin and skin structure
        infections and community-acquired pneumonia
        
        Broad gram (+) and
        (-) pathogens
    - - Spectrum
        
        moderate activity against gram (-)
        
        Used in skin and soft tissue infections, serious infections due
        to MSSA and perioperative surgical prophylaxis
        
        good activity against gram (+)
        
        Do not penetrate CSF
      - e.g.Cephalexin, Cefazolin
  - - - Cefotaxime generally is not
        considered a nephrotoxic drug
- - - - spectrum
        
        limited to aerobic gram-negative bacteria
        including the Enterobacteriaceae and P. aeruginosa.
        
        no gram-positive or anaerobic activity.
        
        more closely resembles that of an
        aminoglycoside.
        
        May be used to replace an aminoglycoside since it is less
        nephrotoxic
      - Therapeutic Uses
        
        • Used successfully for the therapy of a variety of gram (-)
        
        • Not indicated for meningitis
        
        Generally well tolerated
        
        Patients who are allergic to penicillins or cephalosporins, appear not to react to aztreonam
  - - - Imipenem
        
        Imipenem‒Cilastatin
        
        cilastatin competitively inhibits the active tubular
        secretion of imipenem
        
        itself, has no antibacterial activity nor does it
        interfere with imipenem's actions
        
        Cilastatin is a reversible, competitive inhibitor of DHP-1 enzyme, preventing the formation of toxic metabolite of imipenem.
        
        Pharmacokinetics
        
        Administered intravenously
        
        When co-administered with cilastatin, up to 70% of a dose of imipenem can be recovered in unchanged form in urine.
        
        Adverse Reactions
        
        Nausea/vomiting and diarrhea (most common);
        rarely seizures
        
        Patients who are allergic to other β-lactam antibiotics
        may have hypersensitivity reactions with imipenem.
        
        Imipenem is rapidly metabolized by dehydropeptidase1 (DHP-1; an enzyme found in the renal tubule bo
        
        Causes toxicity to the proximal tubule
      - traits that make it an effective
        antibiotic
        
        stability against β-lactamases
        
        Affinity for all bacterial PBPs
        
        More efficient penetration
      - Spectrum
        
        Highly resistant to hydrolysis by most β-lactamases.
        
        Active against a wide variety of: (-)(+)
        
        Has a broader spectrum of activity
        than many other β-lactam antibiotics
        
        Highly active against Enterobacteriaceae that are resistant
        to third-generation cephalosporins.
    - - Less activity against gram-positive cocci than imipenem
      - Meropenem is less nephrotoxic than imipenem
      - Antibacterial activity similar to that of imipenem; also active against some imipenem-resistant Pseudomonas aeruginosa.
      - Less likely to cause seizures; preferred in meningitis when
        carbapenem is required
      - Does not require co-administration with cilastatin (not
        sensitive to renal dehydropeptidase as is imipenem).
- - - - Inhibit many β-lactamases
        
        by
        
        Protect hydrolyzable β-lactam antibiotics
        from inactivation by the β-lactamases
      - Given in combination with the hydrolyzable β-lactams.
        
        example
        
        Amoxicillin + Clavulanic acid = “Augmentin®”
      - No significant antibacterial activity
      - Resemble β-lactams in structure