1st generation Cephalosporins have high similarity to what Penicillins? So?
Main drugs? (2) Oral or Parenteral?
Ampicillin/Amoxicillin + beta-lactamase inhibitor combos
- can enter gram (-) pores OR grapple with gram (+) organisms AND deal with beta-lactamase producing enzymes
Cephalexin (ORAL), Cefazolin (PARENTERAL)
1st generation Cephalosporins are good against what organisms?
- Strep. pyogenes/pneumoniae and Staph. aureus (Penicillin-sensitive strains)
Clinical use for EITHER 1st generation Cephalosporin
Surgical prophylaxis
Good use of Cephalexin RATHER THAN Cefazolin
ORAL –> pharyngitis (good dosing schedule)
- Strep. pyogenes, etc.
3rd generation Cephalosporins - thing what ADDITIONAL coverages besides those from 1st generation? (2)
- CNS infections (meningitis)
- Pseudomonas
3rd generation Cephalosporin drugs (4)
- Ceftriaxone
- Cefotaxime
- Ceftazidime
- Cefaperazone
***Benefits of Ceftriaxone vs. a 1st generation (6)
- Long 1/2 life
- Penetrates CSF and bone
- Treats NEISSERIA (gonorrhea and meningitis)
- Treats Ampicillin-resistant H. Influenza
- Treats BORRELIA (LYME DISEASE in CNS or joints)
- Biliary clearance (easier dosage adjustments)
***Benefit of Cefotaxime vs. a 1st generation
Useful for MENINGITIS due to…
- H. influenza
- S. pneumoniae
- N. meningitidis
- Enteric bacteria
Benefit of Ceftazidime vs. a 1st generation
Pseudomonas coverage…
- Strains resistant to anti-pseudomonal Penicillins - Penicillin allergy
Benefit of Cefaperazone vs. 1st generation
Pseudomonas coverage
Patient is on an antibiotic and develops a flushing reaction after drinking alcohol. What drug was she on?
Cefaperazone
LIKE 1st GENERATION, 3rd generation is good against what organisms?
- S. aureus
- S. pneumoniae
- S. pyogenes
UNLIKE 1st GENERATION, 3rd generation ALSO is good against what organisms?
- Gram (-) rods
- Enteric organisms
ALL 3rd generation drugs are administered how?
Parenteral
In SERIOUS Pseudomonas infection, Ceftazidime or Anti-Pseudomonal Penicillin should ALWAYS be administered with what else?
An aminoglycoside (Tobramycin)
2nd generation Cephalosporin drugs (4) (+ administration route)
- Cefoxitin - PARENTERAL
- Cefotetan - PARENTERAL
- Cefaclor - ORAL
- Cefuroxime axetil - ORAL
2nd generation Cephalosporins are BEST vs. which 2 groups of organisms (compared to 1st generation)?
- Gram (-) – E. coli, Klebsiella (aspiration), H. influenza, Moraxella cattharalis (nose), Proteus
- Anaerobes (B. fragilis, C. diff., Actinomyces, etc.)
Clinical uses of 2nd generation Cephalosporin (2)
- Intra-abdominal or gynecological sepsis
- Intra-abdominal/colorectal surgery
Best 2nd generation Cephalosporins for anaerobic bacteria
Cefoxitin, Cefotetan (i.e. the parenteral ones)
Best 2nd generation Cephalosporin for methicillin-resistant (beta-lactamase producing) organisms
Cefuroxime axetil
Child patient starts an antibiotic and develops a type 3 hypersensitivity (like serum sickness) reaction in her skin and joints. Drug used?
Cefaclor (2nd generation Cephalosporin)
4th generation Cephalosporin drug
Has actions comparable (a little better) to a combo of which other 2 generations?
Cefepime
1st generation (gram (+) w/ beta-lactimase insensitivity) + 3rd generation (gram (-), pseudomonas)
A patient had a Pseudomonas infection and was taking Ceftazidime, but the drug started to wear off. Other option?
Cefepime (4th gen.) - active against Ceftazidime-resistant strains of Pseudomonas
2 potential adverse effects of Cephalosporins
- Hypersensitivity (type 1 anaphylaxis or type 4 rash)
- Disulfiram-like reaction (nausea, flushing, HA w/ alcohol consumption)
A patient had a recent severe hypersensitivity reaction to a Penicillin. Should you give a Cephalosporin instead?
NO
The disulfiram-like reaction seen as an adverse effect to Cephalosporins results from an inhibition of what enzyme? Which causes a build-up of what?
Aldehyde dehydrogenase
Acetaldehyde
A patient is on Warfarin (or has coagulation issues) and develops an independent bacterial infection. You consider administering a Cephalosporin. Which TWO should you be CAUTIOUS of?
Why?
- Cefotetan (2nd gen.)
- Cefaperazone (3rd gen.)
Cause reduced vitamin-K production by GI bacteria –> deficient prothrombin –> BLEEDING potential
Monobactam - drug name (1)
Aztreonam
Aztreonam is effective against which organisms?
Gram (-) rods (Klebsiella, Pseudomonas, Serratia, etc.)
Aztreonam - MoA
Is it active against Gram (+) organisms? Why or why not?
Inhibition of PBP3
NO - the PBP3 is only on gram (-) rods
Is Aztreonam a 1st line therapy? Solo empiric therapy?
When/how is it used generally?
NO and NO
- SUBSTITUTE for Ampicillin/Amoxicillin or Gen 3/4 Cephalosporins IF hypersensitive to these
How is Aztreonam administered?
Parenteral
A severely ill hospitalized patient needs empirical antibiotic therapy for several bacteria, including Gram (+) and Gram (-), as well as Methicillin-sensitive (beta-lactamase) organisms. Good potential option (class)?
Carbapenems
Adverse effects of Carbapenems
- Nephrotoxicity
- CNS toxicity (seizures, confusion)
- Hypersensitivity and rash (caution w/ penicillin allergy)
Imipenem/Cilastatin combo - explain
Imipenem (Carbapenem) is metabolized to a NEPHROTOXIC metabolite via DIPEPTIDASE enzyme.
Cilastatin is a DIPEPTIDASE INHIBITOR, thus preventing the nephrotoxicity and prolonging the effects of Imipenem
Meropenem - benefits over Imipenem (2)
- NOT nephrotoxic OR CNS toxic (less seizure risk)
- Better for bacterial meningitis and intra-abdominal infection
TO REVIEW: Vancomycin is used for which 2 things?
- Penicillin hypersensitivity
2. MRSA or PRSP (penicillin-resistant strep. pneumoniae)
How does Erythromycin differ from Vancomycin? (2)
- MSSA, NOT MRSA or PRSP
- Oral (outpatient) rather than IV Vancomycin (inpatient)
***Use of Clindamycin
WITH Beta Lactam drug - to decrease production of necrotizing/toxic metabolites by certain strep/staph infections that would otherwise cause toxic shock or necrotizing fasciitis (“skin-eating bacteria”)