Review of Antibiotics (Fill in the blanks!

)
Judith L. Rowen, M.D.

Class: -lactams
Name/Type Mode of action Mode of Spectrum of Side Fun Facts
resistance activity Effects/Monitoring
Penicillin Hypersensitivity GABHS still 100%
Diarrhea sensitive.
Bone marrow suppression 1.68 mEq K or Na per
million U

Ampicillin Ditto Ditto Same as above! Active (with

aminoglycoside)
against Enterococcus.
Rash with mono after
4 days.
Penicillinase- Ditto Phlebitis common Dont work for
resistant Renal:________________ Neisseria or
penicillins (monitor for this by Enterococcus.
1. checking_____________)
2. Neutropenia
3. LFT elevations

Ticarcillin Ditto Beta-lactamases May mess up bleeding Contains 5.2 mEq Na

(carboxy- time per gram
penicillin)
Piperacillin Ditto Same as above, plus those 4 times more active
(ureido- for all penicillins than ticarcillin against
penicillin) Pseudomonas.
First generation Ditto Bone marrow suppression
cephalosporins Hypersensitivity (__% Adjust doses for renal
1. PO= cross-reactivity with failure
2. IV= penicillins)
2d generation Ditto As above Oral form tastes awful.
cephalosporins Cefoxitin also in this
1. PO= class; useful for
2. IV= abdominal infections.
Cefaclor (Ceclor)
associated with
erythema multiforme
3rd generation Ditto The same again. Resistant Enterobacter
cephalosporins __________ associated and Citrobacter
1. IM= with biliary sludging (do isolates seen.
2. IV= not administer this drug
3. IV= with intravenous ______ Cefoperazone is in this
4. IV= or precipitates may form.) class, has good biliary
excretion
4th generation Ditto Different dosing
cephalosporin regimen for
IV= fever&neutropenia
Carbapenems Ditto Induce Kills many bugs, but Seizures (imipenem) Imipenem labeled
Imipenem cephalosporinases dont use it unless you even for neonates
Meropenem Imipenem hydrolyzed need it.
by dipeptidase in
brush border; need
cilastatin to inhibit it
Beta-lactamase Ditto Inhibits the beta- Diarrhea Only works for those
inhibitor lactamase of bugs who are resistant
combos: Staphylococcus aureus, by means of beta-
Unasyn many GNR, lactamase, and not all
Augmentin Bacteroides, beta-lactamases at
Zosyn Branhamella/Moraxella that!
Timentin
Class: Vancomycin (glycopeptides)
Vancomycin Mode of action Mechanism of Spectrum of activity Side effects: Use 60 mg/kg for
resistance 1. meningitis.
2. Rapid infusion leads
Monitoring: to:
__________________
Dont use for C. diff;
use Flagyl first

Class: A Smorgasbord of Newer Agents

Daptomycin Mode of action Mechanism of Spectrum of activity Myopathy measure CPK No good for
(Cubicin) Inserts lipid tail resistance MRSA, MSSA, VRE, weekly pneumonia
depolarizesDNA none yet reported, streps, Staph epi Once daily dosing,
RNA, protein resistant lab mutants post-antibiotic effect
synthesis less virulent
disruptedcell death
Quinupristin- Protein synthesis Inactivation, efflux, As above Messes up cytochrome Doesnt work for E.
dalfopristin inhibitor target modification p450, phlebitis use a faecalis
(Synercid) (MLSB mechanisms) central line; incomp. With
Streptogramin B saline, myalgias, conj bili
and A
Linezolid Protein synthesis Mutation in 23S As above Bone marrow suppression Bacteriostatic
(Zyvox) inhibition ribosome binding site Oral bioavailability
oxazolidinone excellent

Class: Aminoglycosides
1. Mode of action Mechanism of Spectrum of activity Side effects: Marked post-antibiotic
resistance 1. effect allows once
2. 2. daily dosing.
3. neuromuscular
3. blockade
Monitoring:
4.

Class: Quinolones
Ciprofloxacin Mode of action Mechanism of Spectrum of activity Side effects Melted cartilage in
Levofloxacin resistance baby beagle hips
means we dont use
them much in Pedi

Class: Tetracyclines
Mode of action Mechanism of Spectrum of activity Avoid under age 9
resistance stains teeth

Class: Glycylcyclines
Mode of action Spectrum of activity Side effects Not used in children
or pregnant women

Class: Macrolides
IV= Mode of action Mechanism of Spectrum of activity GI distress IV administration of
IV= resistance Cholestatic hepatitis erythro may cause
PO= Increases theophylline cardiac arrhythmia
 levels Resistant GABHS
(all side effects less in new increasing
PO macrolides)

Class: Macrocyclics
Fidaxomicin Mode of action Mechanism of Spectrum of activity GI distress Not absorbed. Very
RNA polymerase resistance Used for treatment of - expensive. Fewer
inhibitor, Not sure yet _________________ recurrences compared
bacteriocidal to vancomycin.

Class: Lincosamides
Clindamycin Mode of action Mechanism of Spectrum of activity Antibiotic associated No appreciable CNS
resistance colitis penetration

Class: Chloramphenicol
Chloramphenicol Mode of action Mechanism of Spectrum of activity Aplastic anemia Higher blood levels
resistance Gray-baby syndrome with oral than IV
Prolongs phenytoin half- administration
life

Class: Rifampin
Rifampin Mode of action Mechanism of Spectrum of activity Orange hue to secretions Resistance emerges
resistance Interferes with action of rapidly if used alone
___________________
Gets inside white cells
Class: Imidazole
Metronidazole Mode of action Mechanism of Spectrum of activity Disulfiram reaction Anaerobic gram
resistance Peripheral neuropathy positives less
Encephalopathy, seizures susceptible

Class: Sulfonamides
TMP-SMX Mode of action Mechanism of Spectrum of activity Rash Dose for prophylaxis
resistance Hemolysis in G6PD is 5 mg TMP/25 mg
deficiency SMX per kg/d in 2
Bone marrow suppression doses
Displaces stuff from
albumin, thus may cause Gets inside white
________________ in cells.
neonates

Class: Polymyxins
Colistin Mode of action Mechanism of Spectrum of activity Nephrotoxicity
(Polymyxin E) resistance Last ditch effort against Neurotoxicity
Who knows? resistant -
________________ or
________________
Antimicrobial Use
Test your knowledge

1. A cephalosporin with anti-pseudomonal activity is ________________________

2. The only antibiotic active against 100% of Streptococcus pneumoniae isolates is

_________________

3. True/false. Timentin is a better choice than ticarcillin when treating Pseudomonas.

4. True/false. A reasonable empiric choice to treat a child admitted with cellulitis is vancomycin.

5. Which of the following organisms are best treated with a combination of two antibiotics (more than
one may be correct)?
a. Pseudomonas aeruginosa
b. Enterococcus faecalis
c. Escherichia coli
d. Mycobacterium tuberculosis

6. Which of the following does not have activity against anaerobic organisms?
a. penicillin
b. clindamycin
c. metronidazole (Flagyl)
d. piperacillin
e. none of the above

7. True/false. Group A Streptococcus is always sensitive to penicillin.

8. If you want to know if a Staphylococcus aureus strain is methicillin-resistant, look at the MIC for this
antibiotic. ____________________

9. True/false. If the MIC for drug A is 1 g/ml, and for drug B is 0.5 g/ml, drug B is a better choice.
Ten Commandments of Antimicrobial Use
(From Dr. Schmeckman, Infections in Medicine)

I am the Lord of Antimicrobial Agents. Do not holdeth Antipyretics before me. Antimicrobial agents are
not antipyretics. If you wish to treat a fever do so, but not with antimicrobials.

Thou shalt remember the History and physical and keep it Holy. A good history and physical examination
will be very useful in the diagnosis of infection.

Thou shalt not bear false witness upon the location of the host. You need to distinguish between
community- and hospital-acquired infections.

Thou shalt not forget the little things. Ask about travel, jobs, pets, immunizations, other people with the
same symptoms, etc.

Thou shalt knoweth thy neighbors. Certain organisms cause infections in certain organ systems.

Thou shalt useth what worketh, and thou shalt not covet thy apothecary's new agents without a good
reason. Use antimicrobial agents with proven efficacy for the suspected or known infection.

Thou shalt remembereth primum non nocerum. When given a choice, avoid toxicity.

Thou shalt treateth what thou findeth. When the infection is established and sensitivities known, try to
use the narrowest spectrum agents.

Thou shalt not killeth thy own pharmacy budget. After choosing for high efficacy and lowest toxicity,
consider cost as a variable and try to aim low.

Thou shalt study thy adversary. Learn about the natural history of what you are treating and how it
responds to therapy.

Rowens corollaries to the commandments:

When the heart or brain is infected, shoot to kill. (Dead kidneys are better than a dead patient.)

Vancomycin is a lousy drug, but its all we have, so save it.

If theres no bug, dont use the drug.

Handbooks of drug doses arent perfect.

All antimicrobials have side effects.

Do unto others as you would have them do unto youkeep your pharmacist happy, round off when
reasonable.
Answers to the quiz:

1. Ceftazidime and cefepime

2. Vancomycin
3. False Pseudomonas is not resistant on the basis of clavulanate inhibitable beta lactamase, so
addition of clavulanic acid doesnt help. Ticarcillin is already an anti-Pseudomonal penicillin and
should be fine with an aminoglycoside.
4. False. Vancomycin is not the best choice for a community acquired infection in children even
if MRSA is suspected, the community isolates are usually susceptible to clindamycin and
Bactrim.
5. Pseudomonas is best treated with a beta lactam plus an aminoglycoside. Enterococcus must be
treated with amp+gent or vanc+gent. E. coli is a one-drug-bug. TB requires minimum three
drugs.
6. None of the above penicillin is good against mouth anaerobes, clindamycin is best above the
waist, with gram positive anaerobes, metronidazole is best below the waist with gram negative
anaerobes, and piperacillin has some activity against gram negative anaerobes as well.
7. True. One of the few absolutes in medicine.
8. Oxacillin. No disk is available for methicillin.
9. False. You need to know the achievable concentration of the drug if drug A achieves a
concentration of 100 ug/ml (like a beta lactam), then you are 100x the MIC, whereas if drug B
achieves a concentration of 5 ug/ml (like an aminoglycoside), then you are only 10x the MIC.