Antibiotic Spectra

Cell-Wall Active Agents (B-lactams)

• penicillins

• cephalosporins

• monobactams (not covered b/c not used in Canada much)

• carbapenems

Penicillins

• penicillin

• antistaphylococcal penicillins

  • cloxacillin

• aminopenicillins

  • ampicillin/ amoxicillin

• ureidopenicillins

  • piperacillin

• B-lactam-B-lactamase inhibitors (BL-BLIs)

  • amoxicillin-clavulanic acid

  • piperacillin-tazobactam

Cephalosporins

• 1st generation

  • cephalexin

  • cefazolin

  • cefadroxil

• 2nd generation

  • cefprozil

  • cefurozime

• 3rd generation

  • cefixime

  • ceftriaxone

  • cefotaxime

  • ceftazidime

Carbapenem

• meropenem

• imipenem

• doripenem

• ertapenem

Glycopeptide

• vancomycin

Protein Synthesis Inhibitors

• tetracyclines

• macrolides

• lincosamide

Tetracycline

• doxycycline

Macrolides

• clarithromycin

• azithromycin

Lincosamine

• clindamycin

DNA Synthesis Inhibitors

• fluoroquinolones

  • norfloxacin

  • ciprofloxacin

  • levofloxacin

  • moxifloxacin

Lancefield group strep

• all penicillins

• all cephalosporins

  • except ceftazidime

• all carbapenems

• vancomycin

• doxycycline (resistance >10%)

• all macrolides (resistance >10%)

• clindamycin

• all fluoroquinolones

  • except norfloxacin

Staphylococcus aureus (MSSA)

• cloxacillin

• all BL-BLIs

• all 1st and 2nd generation cephalosporins

• 3rd generation cephalosporins

  • ceftriaxone

  • cefotaxime

• all carbapenems

• vancomycin

• doxycycline

• all macrolides (resistance >10%)

• clindamycin

• all fluoroquinolones (resistance >10%)

  • except norfloxacin

Staphylococcus aureus (MRSA)

• ceftriaxone

• cefotaxime

• ertapenem

• vancomycin

• doxycycline

Streptococcus pneumoniae

• all penicillins (resistance >10%)

  • penicillin G,V moderate coverage

• all BL-BLIs (resistance >10%)

• 1st generation cephalosporins (resistance >10%)

• 2nd generation cephalosporins (resistance >10%)

  • what is commonly used

• cefixime (resistance >10%)

• meropenem, imipenem, doripenem

• vancomycin

• doxycyclines (resistance >10%)

• all macrolides (resistance >10%)

• clindamycin

  • not often used

• levofloxacin

• moxifloxacin

Enterococcus faecalis

• all penicillins

  • except cloxacillin

• all BL-BLIs

• meropenem, imipenem, doripenem

  • best coverage with imipenem

• vancomycin

• doxycycline (resistance >10%)

  • UTI only

• all fluoroquinolones

  • except moxifloxacin

  • UTI only

Enterococcus faecium

• vancomycin

• doxycycline (resistance >10%)

  • UTI only

Haemophilus influenzae

• all penicillins (resistance >10%)

  • except cloxacillin

• all BL-BLIs

• 1st generation cephalosporins (resistance >10%)

• all 2nd and 3rd generations

  • ceftazidime (resistance >10%)

• all carbapenems

• doxycycline

• all macrolides

• all fluoroquinolones

  • except norfloxacin

Escherichia coli

• ampicillin, amoxicillin (resistance >10%)

• piperacillin (resistance >10%)

• amoxicillin-clavulanic acid (resistance >10%)

• piperacillin-tazobactam

• all cephalosporins

• all carbapenems

• doxycycline

• all fluoroquinolones (resistance >10%)

Proteus mirabilis

• ampicillin, amoxicillin (resistance >10%)

• piperacillin (resistance >10%)

• all BL-BLIs

• all cephalosporins

• all carbapenems

• all fluoroquinolones (resistance >10%)

Klebsiella pneumoniae

• all BL-BLIs

• all cephalosporins

• all carbapenems

• all fluoroquinolones

Pseudomonas aeruginosa

• piperacillin (resistance >10%)

• piperacillin-tazobactam

• ceftazidime

• meropenem, imipenem, doripenem

• all fluoroquinolones (resistance >10%)

  • except moxifloxacin

  • ciprofloxacin is FQ of choice

Oral anaerobes

• all except:

  • cloxacillin

  • norfloxacin

  • ciprofloxacin

Atypicals (Chlamydophila pneumoniae, Mycoplasma pneumoniae, Legionella spp.)

• doxycycline

• all macrolides

• all fluoroquinolones

  • except norfloxacin

Bacteroides fragilis

• all carbapenems

• clindamycin (resistance >10%)

• moxifloxacin (resistance >10%)

• metronidazole

Intrinsic resistance

inherent ability of a species to oppose activity of a particular agent because of its structural or functional characteristics

Acquired resistance

strain or subpopulation of a species the gains the ability to oppose activity of an agent to which it was previously susceptible

generally due to horizontal gene transfer or selective pressure from antimicrobial therapy

Why did S. aureus stop being tested for penicillin susceptibility?

• resistance became so prevalent it wasn’t worth testing for susceptibility against penicillin anymore (only 5% of S. aureus are still susceptible worldwide)

• wild-type S. aureus is now MSSA (methicillin susceptible S. aureus); same pathogen, different susceptibilities, same virulence

  • methicillin was prototype for cloxacillin

Why does gram-negative bacteria have better resistance versus gram-positive bacteria?

• having an outer cell membrane allows for greater resistance to B-lactams

  • because B-lactams have to work on peptidoglycan layer the outer membrane blocks access

• B-lactamases can’t diffuse away like they can in gram-positive bacteria because of outer membrane

  • B-lactamases able to accumulate between inner and outer cell membranes

  • when antibacterial agent gets access it enters an area very concentrated in B-lactamases so more likely to be broken down

Most common mechanism of resistance to Lancefield group strep

none

Most common mechanism of resistance to Staphylococcus aureus

B-lactamase

Most common mechanism of resistance to Streptococcus pneumoniae

altered PBP, where modification isn’t drastic enough that the penicillin can’t fit will just need an increase in dose to give enough opportunity for it to finally fit

Most common mechanism of resistance to Enterococcus faecalis

B-lactamase

Most common mechanism of resistance to Enterococcus faecium

altered PBP, significant alteration so no penicillin agents have activity

Most common mechanism of resistance to gram-negatives

• decreased penetration

• altered porin channels

• concentrated B-lactamases

Most common mechanism of resistance to Chlamydophila pneumoniae & Legionella spp.

both are intracellular pathogens and B-lactams don’t penetrate into host cells, so will have no activity

Most common mechanism of resistance to Mycoplasma pneumoniae

no cell wall, so cell wall inhibitors aren’t going to work

Most common mechanism of resistance to anaerobes, especially Bacteroides fragilis

B-lactamase

Why does ampicillin and amoxicillin have greater gram-negative activity versus penicillin/cloxacillin?

it is better able to get into the porin channels than other penicillins

Why does piperacillin have greater gram-negative activity versus ampicillin/amoxicillin?

everything same but gained pseudomonas aeruginosa because even better at getting through outer membrane of gram-negatives

Why does amoxicillin-clavulanic acid have greater activity towards gram-negatives, S. aureus and B. fragilis?

the clavulanic acid is a B-lactamase inhibitor so you get better activity in bacteria that create B-lactamases: S. aureus, gram-negatives and B. fragilis

does not improve activity against S. pneumoniae because resistance is from altered PBP

Why does piperacillin-tazobactam have greater activity towards gram-negatives versus amoxi-clav?

activity towards all gram-negatives because tazobactam is a better B-lactamase inhibitor than clavulanic acid, so get lots of coverage

Why does cloxacillin have activity against S. aureus, but lose complete activity against gram-negative bacteria?

has a large side chain, preventing binding of S. aureus’ B-lactamase, but loses penetrating ability into gram-negative outer membrane

What is the main difference between 1st generation and 2nd generation cephalosporins?

2nd generation has more activity against H. influenza (from >10% to <10%) and is more potent against S. pneumoniae, even though still >10% resistance

What is the main difference between oral 3rd generation and IV 3rd (ceftriaxone & cefotaxime) generation cephalosporins?

oral: loss of S. aureus from 2nd generation

IV: get reliable activity of S. aureus and S. pneumoniae

How does ceftazidime differ from the other 3rd generation cephalosporins?

no activity for gram-positive bacteria

activity against P. aeruginosa

Does gram-negative potency go up or down with increasing generations of cephalosporins?

with increasing generations gram-negative potency increases, and also thought that staphylococcal potency decreases

Besides cloxacillin what are other alternatives for MSSA?

1st generation cephalosporins (cefazolin, cephalexin, cephadroxil), may also be better in community as do not need to be taken on an empty stomach

Which cephalosporins can be used against S. pneumoniae and worried about meningitis?

3rd generation, ceftriaxone and cefotaxime, because has excellent coverage and can cross the blood-brain barrier

When would you use ertapenem over the other carbapenems?

ertapenem doesn’t have activity against E. faecalis or P. aeruginosa so would use it when you don’t want to put selective pressure on these 2 bacteria types

What is the drug of choice for MRSA and E. faecium?

Vancomycin

Would vancomycin be preferred for MSSA?

vancomycin is inferior to cloxacillin for MSSA, even though effective for MRSA

Is moxifloxacin appropriate for treatment of UTIs?

does not get cleared renally for not appropriate for UTIs

Which fluoroquinolone has best gram-negative and P. aeruginosa coverage?

ciprofloxacin

Which fluoroquinolones are considered respiratory fluoroquinolones?

levofloxacin and moxifloxacin, because they have the best gram-positive coverage including S. pneumoniae

Which agents have broad spectrum activity?

• BL-BLIs

• carbapenems

• fluoroquinolones

Which agents have narrow spectrum activity?

• cloxacillin

• ceftazidime

• vancomycin

• metronidazole