Are penicillin antibiotics bactericidal or bacteriostatic?
Bactericidal for gram + cocci/rods, gram - cocci and spirochetes.
What must penicillin antibiotics be able to do to be effective antibiotics?
1) Penetrate the cell layer in gram negative organisms 2) Maintain the beta-lactam ring 3) Bind transpeptidase and other penicillin binding proteins
How do gram negative organisms specifically alter themselves to become resistant to beta-lactam antibiotics?
Alter their porins and prevent beta-lactam passage through the outer membrane to the inner cell wall.
How do gram positive and gram negatives gain resistance to penicillins?
Gram positive organisms secrete beta-lactamases and gram-negative organisms have beta-lactamases bound to their cytoplasm. Both types of organisms can also alter the structure of their transpeptidase and prevent binding of the beta-lactams.
Common adverse reactions associated with penicillin antibiotics
1) IgE-mediated anaphylaxis 2) Delayed rash that appears days to weeks later 3) GI symptoms from destruction of normal flora
5 types of penicillins?
1) Penicillin 2) Aminopenicillin 3) Penicillinase-resistant penicillin 4) Anti-Pseudomonal Penicillin 5) Cephalosporin
Route of administration for penicillin G and V? Common uses for both?
G = IM/IV (sometimes used for s. aureus pneumonia). V = oral (sometimes used for group A strep pharyngitis).
Common penicillin antibiotics used for bronchitis, UTIs and sinusitis caused by gram-negative bacteria?
Aminopenicillins (ampicillin and amoxicillin). They penetrate gram-negative outer membranes better and thus cover more gram-negative organisms like E. coli, Proteus, Salmonella, Shigella (enterics), H. influenzae and L. monocytogenes. They are also one of the few drugs that work against gram-positive enterococci. Note that they are still susceptible to beta-lactamase.
When would you consider using the “Amp-gent” combo in the hospital?
Combining ampicillin (an aminopenicillin) with gentamycin (an aminoglycoside) provides broad spectrum coverage against gram-negative enteric organisms that cause UTIs. This is useful while you are waiting for cultures to tell you the exact organism.
Penicillin antibiotics that are the drugs of choice for serious s. aureus infections that cause cellulitis, endocarditis and sepsis.
IV penicillinase-resistant penicillins, nafcillin, oxacillin, methicillin (unless it is MRSA). You can also give oral cloxacillin and dicloxacillin.
What organisms are not well controlled by penicillinase-resistant penicillins?
Penicillin antibiotics that are used for pneumonia and sepsis caused by Pseudomonas aeruginosa and gram - rods.
Anti-pseudomonal penicillins. These include the carboxypenicillins: ticarcillin/carbenicillin and the ureidopenicillins: piperacillin/mezlocillin. These are often combined with aminoglycosides as “Pip-gent” and “Ticar-gent” for synergism against pseudomonas.
What organisms are not well controlled by anti-pseudomonal penicillins?
S. aureus. These antibiotics are susceptible to penicillinases.
What can you add to a beta-lactam that extends coverage to beta-lactamase producing gram-positives (S. aureus), gram-negatives (H. influenza) and anaerobes (Bacteroides)?
The beta-lactamase inhibitors clavulanic acid, sulbactam and tazobactam
What advantages do the cephalosporin antibiotics have over the beta-lactams? Organisms typically not covered by cephalosporins?
1) More resistant to beta-lactamases 2) Increased variability in coverage. Listeria, Atypicals (chlamydia/mycoplasma), MRSA and Enterococci are typically not covered (except ceftaroline).
How does coverage change as you go from first, to second, to third and fourth generation cephalosporins?
Increased control of gram-negative organisms and decreased control of gram-positive organisms. Note that the 4th generation has good coverage of BOTH gram negative and gram positive organisms.
Why are MRSA and enterococci resistant to all cephalosporins?
These organisms have changed the structure of their penicillin-binding proteins.
What cephalosporins are commonly used in patients with Proteus, E. coli, Klebsiella, Staph/strep infections that are allergic to penicillin AND/OR in patients having surgery for prophylaxis against skin infections (S. aureus)?
1st generations. Most start with “ceph” (like cephalexin). Just remember that cefazolin and cefadroxil are the exception to this rule and are also 1st generation cephalosporins.
What cephalosporins are commonly used in patients infected by gram + cocci, H. influenzae, Enterobacter, Neisseria, Proteus, E. coli, Klebsiella and Serratia?
2nd generations. They have “fam, fa, fur, fox and te” in their names. (ceFAMandole, ceFAclor, ceFURoxime, ceFOXitin, cefoTEtan). The exceptions are cefmetazole, cefonicid, cefprozil and loracarbef.
What cephalosporins are commonly used in patients with nosocomial pneumonia, meningitis, sepsis, gonorrhea and UTIs caused by multi-drug resistant aerobic gram-negative organisms?
3rd generations. Most have “t” in the name (cefTriaxone, cefTazidime, etc.). The exceptions are cefixime, cefoperazone, cefpodoxin. Note that cefoTetan has a “t” but it is a second generation.
What cephalosporins have increased activity against pseudomonas and gram + organisms?
4th generation: Cefepime
Common adverse reactions associated with cephalosporins
10% cross-reactivity w/penicillin: 1) IgE-mediated anaphylaxis 2) Delayed rash.
What cephalosporin is commonly used in patient’s with community-acquired bacterial pneumonia before you know what the causative organism is? What other condition is this commonly used to treat?
Second-generation cefuroxime has good coverage against S. pneumoniae and H. influenzae. It is also used for sinusitis and otitis media caused by H. influenzae and B. catarrhalis.
What cephalosporins provide good coverage of anaerobic bacteria like Bacteroides and are consequently used for intra-abdominal infections, aspiration pneumonia and colorectal surgery prophylaxis?
Second generation: cefotetan, cefoxitin and cefmetazole.
3rd generation cephalosporin most often used for hospital-acquired meningitis caused by MDR gram-negative organisms? What other organism is it 1st line therapy treatment for?
Ceftriaxone has the best CNS penetration of the 3rd generation cephalosporins and is the 1st line drug for meningitis in neonates, children and adults. It is also 1st line for N. gonorrhoeae.
What are the only cephalosporins that are effective for treating pseudomonas?
Ceftazidime (3rd), cefoperazone (3rd) and cefepime (4th).
4 classes of beta-lactam antibiotics
1) Penicillin family 2) Cephalosporins 3) Carbapenems 4) Monobactams
What antibiotics have the broadest antibacterial activity of any of the antibiotics known? What is its Achilles heel?
Imipenem, ertapenem, meropenem, doripenem (from the carbapenem beta-lactam family). It is small (can pass through all sorts of porin channels) and beta-lactamase resistant. It covers gram - rods, gram + cocci and anaerobes (including pseudomonas and enterococcus). Its Achilles heel is MRSA, some pseudomonas and mycoplasma.
Why is cilastin given with imipenem and not meropenem?
Cilastin inhibits renal dihydropeptidase, the enzyme that breaks down imipenem. Meropenem is stable against dihydropeptidase.
Common adverse reactions associated with imipenem and meropenem
Cross-reactivity w/penicillin 1) IgE-mediated anaphylaxis and 2) Delayed rash. It also lowers the seizure threshold (fewer seizures w/meropenem).