Antibiotics

Things to keep in your lab coat.

The Sanford Guide to Antimicrobial

Therapy
Johns Hopkins Abx Guide (not free any
more)
Palm
oiSilo program
oEpocrates
 Tips for the boards
Study hard and efficiently. Dont waste time on a
resource that isnt making sense.
Get the landscape first then the landmarks.
Dont be afraid to study outside of the review
books.
Think like a question writer. Anticipate questions
for each topic.
Forget about learning everything because the
gaps in your knowledge will be random.
 Gram-positives Gram-negatives
Imipenem
Anti-staph PCNs Meropenem Anti-pseudomonal PCNs
(nafcillin, methicillin, (pipercillin, ticarcillin,
Amoxicilli
oxacillins) carbenicillin)
n
Ampicillin
Macrolides
Penicillin G/V
Clindamycin
Linezolid
Fluoroquinolines
Vancomyci Aztreonam
Rifampin
n
Sulfonamides
Aminoglycosides
Tetracyclines

Cephalosporin
1st Generation s3rd Generation 2nd Generation
How to approach the daunting task
of learning antibiotics

Create a general rule and know the

exception to the rule.
 Rule: All cell-wall inhibitors are beta-lactams,
except vancomycin.

Beta-lactam ABX Exception

o Penicillins o Vancomycin
o Cephalosporins
o Aztreonam
o Carbapenems
Beta-lactam structure
Gram-positive vs. Gram-negative
 Mechanism of Action

1.All beta-lactams bind penicillin-binding

proteins (PBPs)
2.All beta-lactams block transpeptidase
cross-linking of cell wall
3.Activate autolytic enzymes, causing
osmotic damage (bactericidal)
 Beta-lactams:
1st mechanism of resistance
Beta-lactamase production (i.e. S. aureus)
We can get around this mode of resistance by
making beta-lactamase resistant penicillins (i.e.
nafcillin)
 Beta-lactams:
2nd mechanism of resistance
Change the structure of PBPs
(i.e. Methicillin-Resistant S. Aureus)

Once bugs have changed their PBPs, we only

have one drug that will work, vancomycin.
 Beta-lactams:
3rd mechanism of resistance
Efflux pump or change in porin structure:
Relevant for gram-negative bacteria
 Summary of resistances to beta-
lactamases
1st beta-lactamase production (S. aureus)
2nd change in PBP (MRSA)
3rd efflux pump or change in porin structure
(gram-negatives i.e. pseudomonas)
 1st Generation
Drugs
o Penicillin G and V
Clinical use
o Narrow spectrum (mainly gram-positives)
Sensitive to beta-lactamases
o Means: on an exam, penicillin G or V is never the
answer for treating Staph
Exam questions:
o DOC for syphillis (benzathine penicillin),
o DOC in strep infections, especially to prevent
rheumatic fever
o DOC for susceptible pneumococci
 2nd Generation

Drugs
oNafcillin, Methicillin, Oxacillin, Cloxacillin,
Diclaxicillin
To overcome the beta-lactamase resistance,
these drugs were developed but they became so
narrow spectrum that they only clinically are
used for Staph.
These drugs created the superbug MRSA
o Beta-lactamase
 3rd Generation
Drugs
o Aminopenicillins
Ampicillin
Amoxicillin
Clinical use
o Broad spectrum (gram positive and gram negatives, but NOT
beta-lactamase resistant)
Famous for treating:
H. flu and Listeria (ampicillin)
Lyme Disease (amox) DOC in peds and pregnancy
Enterococci
o Drug companies made body guards, clavulanic acid and
sulbactam, to protect the aminopenicillins from beta-lactamases.
 4th Generation

Drugs
o Anti-pseudomonal penicillins
Ticarcillin
Piperacillin
Carbenicillin

Clinical use
Pseudomonas
Synergistic effect when combined with aminoglycosides.
Parenteral penicillins usually combined with beta-lactamase
inhibitors
Pharmacokinetics of Penicillins
Rule: All penicillins are water soluble, except nafcillin.

Water soluble substances:

o Are excreted by the kidneys.
Means adjustments in renal failure and are potentially renal toxic
o Do not cross the blood brain barrier
Means no good for meningitis
Lipid soluble substances:
o Are metabolized in the liver
Means many p450 interactions
o Cross the blood brain barrier
Means could potentially be used for meningitis
 Toxicity
Rule: Penicillins cause allergies
o Come from fungal organisms
Means already immunogenic
o Contain sulfur to enhance solubility
Means bad for allergies
o Can cause ANY hypersensitivity reaction (Type I-IV)
Methicillin famous for interstitial nephritis (type III)
Hapten mediated hemolysis
About 5-10% cross-allergenicity with cephalosporins
 Toxicity
Jarisch-Herxheimer reaction in Rx of syphilis
oFever, chills, headache, myalgias, and
exacerbation of syphilitic cutaneous lesions
Ampicillin causes a famous maculopapular rash
when given to patients with infectious mono
(EBV).
 Cephalosporins

Mechanism of action and resistance:

osame as penicillins
1st Generation Cephalosporins
Drugs
o Any drug with ph in name b/c from Europe
Cephalexin, cephradine
Except cefazolin (famous for surgical prophylaxis b/c of long
half-life)

Clinical use
o Gram positives
And a few gram negatives PEcK (Proteus, E. coli, Klebsiella)

Pharmacokinetics
o Do not enter CNS
2nd Generation Cephalosporins

Drugs
oCefoxitin, cefaclor, cefuroxime
Clinical use
oGram negatives: HEN PEcKS (H. flu,
Enterobacter, Neisseria, Proteus, E. coli,
Klebsiella, Serratia)
Pharmacokinetics
oDo not enter CNS, except cefuroxime
3rd Generation Cephalosporins
Drugs
o Ceftriaxone, cefotaxime, ceftazidime
o notice the ts
Clinical use
o 1st generation + 2nd generation = 3rd generation (gram positive
and negative) +anaerobes
Pharmacokinetics
o Ceftriaxone is lipid soluble
Means good entry into CNS
Means metabolized and excreted into bowel
Can cause sludge in gallbladder

Boards:
o Ceftazidime for pseudomonaz
o Ceftriaxone for gonorrhea and meningitis
4th Generation Cephalosporins

Drugs
oCefepime
oCefpirome
Clinical use
o3rd Generation + more beta-lactamase
resistance
 Toxicity

Same as penicillins
Disuliram-like reaction w/ ethanol
oIn cephalosporins with a methylthiotetrazole
group, i.e. cefamandole, cefoperazone,
cefotetan
azole portion gives us the disulfiram-like reaction
Metronidazole
 Aztreonam

Mechanism:
oMonobactam resistant to beta-lactamases
oInhibits cell wall synthesis (same as penicillins)
oSynergistic with aminoglycosides
Clinical use
oGram negative rods only (pseudomonas)
Toxicity
oNo cross-allergenicity w/ penicillins
 Imipenem/cilastatin, Meropenem

Mechanism
o Carbapenems resistant to beta-lactamases
o Inhibits cell wall synthesis (same as penicillins)
o Cilastatin inhibits renal dihydropeptidase I which
decreased inactivation of imipenem in kidney.
Clinical use
o Decerebrate Antibiotics
Dont need to think about coverage, can work on almost
anything
Toxicity
o Imipenem famous for CNS toxicity (seizures)
o Meropenem has reduced risk of seizures
 Vancomycin
Mechanism
o Inhibits cell wall mucopeptide formation by binding
o D-ala D-ala portion of cell wall precursors (USMLE TQ)
Resistance occurs when changed to D-ala D-lac
Clinical use
o Gram positive multidrug-resistant organisms
MRSA (IV)
C. difficile (PO)
Toxicity
o Nephro and ototoxic
o Red man syndrome with rapid infusion
Can prevent w/ antihistamine pretreatment
 Gram-positives Gram-negatives
Imipenem
Anti-staph PCNs Meropenem Anti-pseudomonal PCNs
(nafcillin, methicillin, (pipercillin, ticarcillin,
Amoxicilli
oxacillins) carbenicillin)
n
Ampicillin
Penicillin G/V

50s ribosome

Vancomyci Aztreonam
Nucleus
n

30s ribosome

Cephalosporin
1st Generation s3rd Generation 2nd Generation
 Protein Synthesis Inhibitors

Rule: All protein synthesis inhibitors are

bacteriostatic, except for the
aminoglycosides.
 Tetracyclines

Drugs
o Doxycycline
o Minocycline
o Demeclocycline
o Tetracycline

Mechanism
o Reversibly bind to the
30S ribosome and
inhibit binding of
aminoacyl-t-RNA to the
 Tetracyclines
Clinical use
o Very broad spectrum
o Important use for spirochetes and intracellular bugs
Rickettsial Infections
Chlamydia
Toxicity
o Chelators of divalent ions
Means they deposit in bones and teeth
Means contraindicated in pregnancy and in kids who are still growing
Means cant take with antacids or iron.
o GI distress
o Fanconis syndrome
o Photosensitivity
Boards:
o Doxycycline is lipid soluble; means good STDs and prostatitis
o Minocycline is very water soluble and enters all secretions, especially saliva;
means useful for meningococcus prophylaxis
o Demeclocycline inhibits the release of ADH; means can be used for SIADH
 Aminoglycosides
Drugs
o Gentamycin, neomycin, amikacin, tobramycin, streptomycin
Mechanism
o Taken up by an oxygen dependent pump and bind to the 30S ribosomal unit
and Induce the binding of the wrong t-RNA-AA complex, resulting in the
synthesis of false proteins. (Bactericidal)
 Aminoglycosides
Clinical use
o Gram negative aerobes only!
(pseudomonas)
oSynergistic w/ beta-lactams
o Neomycin for bowel surgery
o Tobramycin for Pseudomonas
Toxicity
o Amino (NH3) + glycoside (OH) makes
extremely polar
Means membrane penetration in a
bacteria is dependent on a special
oxygen pump and only covers gram
negative aerobes
Means renally excreted and renal toxic
Means can be trapped in inner ear and
is ototoxic
o Neuromuscular blockade
 Macrolides
Drugs:
o Erythromycin
o Azithromycin
o Clarithromycin
Mechanism
o Inhibit protein synthesis
by blocking
translocation, bind to
50S ribosomal subunit
(resistance is through
methylation at binding
site)
 Macrolides
Clinical use
o Same broad coverage as tetracyclines
o URIs and atypical pneumonias (Mycoplasma,
Legionella, Chlamydia)
o Neisseria
o Alternative for penicillin allergic patients
Toxicities
o Stimulate motilin receptor (erythromycin) causing GI
upset
o Lipid soluble, except azithromycin
Means P450 interactions (erythromycin is a famous inhibitor)
and liver problems (acute cholestatic hepatitis)
 Clindamycin

Mechanism
oBlocks peptide bond formation at 50S
ribosomal subunit (bacteriostatic)
Clinical use
oGram-positives and anaerobes
Means can easily cause C. diff colitis
oGood penetration into bones
Means can be used for S. aureus osteomyelitis
 Linezolid
Mechanism
o Linezolid binds on the 23S portion of the 50S subunit close to the
peptidyl transferase and chloramphenicol binding sites.
Clinical
o Famous for treating gram-positive drug resistant bugs (MRSA,
and multidrug resistant pneumococcus)
Toxicity
o Usually well tolerated
o Thrombocytopenia
o MAOI (avoid tyramine containing food)
 Quinupristin/Dalfopristin
Mechanism
o Protein synthesis inhibitors that bind the 50S
ribosomal subunit
Clinical use
o VRE
Toxicity
o P-450 inhibitor
Inhibitors of DNA synthesis

Fluoroquinolones
Rifampin
Sulfonamides
 Fluoroquinolones
Drugs
o Ciprofloxacin
o Gatifloxacin
o Levofloxacin
o Moxifloxacin
o Ofloxacin
Mechanism
o Inhibits DNA gyrase (topoisomerase II) (Bactericidal)
 Fluoroquinolones
Clinical use
o Gram-negative rods of UTI and diarrhea
o Were 1st oral treatment of gram-negative sepsis
Means were overused, leading to resistance
o Distributes into all tissues and fluids (including bones)
Means can inhibit cartilage and tendon damage leading to tendonitis
and tendon rupture in adults
Means can be used for Salmonella osteomyelitis
Means contraindicated in pregnancy and in children
o Respiratory fluoroquinolones (levofloxacin) for drug resistant
pneumococcus
o Anthrax (ciprofloxacin)
Toxicity
o QT prolongation and arrhythmias
o Hypo/hyperglycemia
o Achilles tendon rupture or tendinitis has occurred rarely
 Rifampin
Mechanism
o Inhibits DNA-dependent RNA polymerase
Clinical use
o TB (in combo and in prophylaxis)
o Famous for prophylaxis of meningococcus and H. flu
Toxicity
o Hepatotoxic
o Revs up P-450
o Rs:
RNA polymerase inhibitor
Revs up P-450
Red/orange body fluids
Sulfonamides and Trimethoprim
 Sulfonamides

Mechanism
oInhibits bacterial dihydropteroate synthase
by competing for binding sites with p-
aminobenzoic acid (PABA), a precursor
required for bacterial synthesis of folic acid.
oTrimethoprim binds tightly to bacterial
dihydrofolate reductase. Synergistic with
sulfonamides.
 Sulfonamides
Clinical use
o Resistance to sulfonamides is common
o PCP prophylaxis (PO) and treatment (IV)
TrimethoprimSulfamethoxazole, (TMP-SMX)
If sulfa allergy use pentamidine (antiprotozoal agent)
o Toxoplasmosis (Pyrimethamine + Sulfadiazine)
Toxicity
o Allergies (sulfa allergies, hemolytic anemia, SJS)
o Carried by albumin
Means can cause kernicterus
o Crystalluria
o Folic acid can be given to avoid some toxicities
 Metronidazole
Mechanism
o Toxic metabolites
Means causes GI disturbance, glossitis (metallic taste in
mouth), urethritis
Clinical use
o Anaerobes
o G.E.T. on the Metro (Giardia, Entamoeba,
Trichomonas)
o C. diff colitis (PO)
Toxicity
o Metronidazole
Disulfiram-like reaction w/ ethanol
Mechanisms of Resistance
 How to approach antibiotic
coverage

Rule: Every bacteria is gram negative,

except for the gram-positives and oddballs.
Exceptions to everything is gram-
negative
Gram-positives Oddballs
o Staph/Strep o Mycoplasma (no cell wall)
o Listeria o Ureaplasma (no cell wall)
o Bacillus o Legionella (silver stain)
o Clostridium o Chlamydia (obligate
o Corynebacterium intracellular)
o Rickettsia (obligate
intracellular)
o Mycobacterium (acid-fast)
o Treponema (spirochete)
o Borrelia (spirochete)
Gram-positives Gram-negatives

Cell
Wall

50s ribosome

Nucleus

30s ribosome
Gram-positives Gram-negatives

Cell
Wall

50s ribosome

Vancomyci Aztreonam
Nucleus
n

30s ribosome
 Gram-positives Gram-negatives

Anti-staph PCNs Anti-pseudomonal PCNs

(nafcillin, methicillin, (pipercillin, ticarcillin,
oxacillins) carbenicillin)
Cell
Wall
Penicillin G/V

50s ribosome

Vancomyci Aztreonam
Nucleus
n

30s ribosome
 Gram-positives Gram-negatives

Anti-staph PCNs Anti-pseudomonal PCNs

(nafcillin, methicillin, (pipercillin, ticarcillin,
oxacillins) carbenicillin)
Cell
Wall
Penicillin G/V

50s ribosome

Vancomyci Aztreonam
Nucleus
n

30s ribosome

Cephalosporin
1st Generation s3rd Generation 2nd Generation
 Gram-positives Gram-negatives

Anti-staph PCNs Anti-pseudomonal PCNs

(nafcillin, methicillin, (pipercillin, ticarcillin,
Amoxicilli
oxacillins) carbenicillin)
n
Ampicillin
Penicillin G/V

50s ribosome

Vancomyci Aztreonam
Nucleus
n

30s ribosome

Cephalosporin
1st Generation s3rd Generation 2nd Generation
 Gram-positives Gram-negatives
Imipenem
Anti-staph PCNs Meropenem Anti-pseudomonal PCNs
(nafcillin, methicillin, (pipercillin, ticarcillin,
Amoxicilli
oxacillins) carbenicillin)
n
Ampicillin
Penicillin G/V

50s ribosome

Vancomyci Aztreonam
Nucleus
n

30s ribosome

Cephalosporin
1st Generation s3rd Generation 2nd Generation
 Gram-positives Gram-negatives
Imipenem
Anti-staph PCNs Meropenem Anti-pseudomonal PCNs
(nafcillin, methicillin, (pipercillin, ticarcillin,
Amoxicilli
oxacillins) carbenicillin)
n
Ampicillin
Macrolides
Penicillin G/V
Clindamycin
Linezolid

Vancomyci Aztreonam
Nucleus
n

Aminoglycosides
Tetracyclines

Cephalosporin
1st Generation s3rd Generation 2nd Generation
 Gram-positives Gram-negatives
Imipenem
Anti-staph PCNs Meropenem Anti-pseudomonal PCNs
(nafcillin, methicillin, (pipercillin, ticarcillin,
Amoxicilli
oxacillins) carbenicillin)
n
Ampicillin
Macrolides
Penicillin G/V
Clindamycin
Linezolid
Fluoroquinolines
Vancomyci Aztreonam
Rifampin
n
Sulfonamides
Aminoglycosides
Tetracyclines

Cephalosporin
1st Generation s3rd Generation 2nd Generation
My rules for antibiotics questions.

Is the bug gram-positive or gram-negative?

o Use the chart we just made for what antibiotic to use
Look for contraindications to using your
antibiotic. Is the patient too young or too
pregnant?
o Dont use tetracyclines, aminoglycosides,
fluoroquinolones, sulfonamides.
Is the bug intracellular
o Use a tetracycline or macrolide
Antibacterial Drugs in Pregnancy
Antibacterial Toxicity in Pregnancy Recommendation
Drug
Aminoglycosides Possible 8th nerve toxicity Cautiona

Chloramphenicol Gray syndrome in newborn Caution at term

Fluoroquinolones Arthropathy in immature animals Caution

Clarithromycin Teratogenicity in animals Contraindicated

Ertapenem Decreased weight in animals Caution

Erythromycin Cholestatic hepatitis Contraindicated

estolate
Imipenem/cilastatin Toxicity in some pregnant animals Caution

Linezolid Embryonic and fetal toxicity in rats Caution

Meropenem Unknown Caution

Metronidazole None known, but carcinogenic in rats Caution

Nitrofurantoin Hemolytic anemia in newborns Caution; contraindicated at

term
Quinupristin/dalfop Unknown Caution
ristin
Sulfonamides Hemolysis in newborn with G6PDb deficiency; kernicterus in Caution; contraindicated at
newborn term

Tetracyclines Tooth discoloration, inhibition of bone growth in fetus; hepatotoxicity Contraindicated

Vancomycin Unknown Caution

GBS, E. coli, H. flu, Listeria, Meningococcus, Pneumococcus

Newbor Adul
n t
 Practice Question
A 16-year-old high school cheerleader presents
with low grade fever, pleuritic pain and a non-
productive cough. A sample tube of her blood was
placed in ice, and "grains of sand" appeared in the
glass portion of the tube. Therapy should include
which of the following?
A. Ampicillin
B. Erythromycin
C. Oxygen and external cooling
D. Penicillin G
E. Ribavirin
 Practice Question
A 58-year-old alcoholic man with multiple dental caries
develops a pulmonary abscess and is treated with
antibiotics. Several days later, he develops nausea,
vomiting, abdominal pain, and voluminous green diarrhea.
Which of the following antibiotics is most likely responsible
for this patient's symptoms?
A. Chloramphenicol
B. Clindamycin
C. Gentamicin
D. Metronidazole
E. Vancomycin
 Practice Question

Which of the following organisms is most

likely to be implicated as a cause of
urethritis that persists after antibiotic therapy
for gonorrhea?
A. Actinomyces
B. Chlamydia
C. Mycobacteria
D. Nocardia
E. Rickettsia
 Practice Question
A 33-year-old woman presents with fever, vomiting, severe
irritative voiding symptoms, and pronounced costovertebral
angle tenderness. Laboratory evaluation reveals
leukocytosis with a left shift; blood cultures indicate
bacteremia. Urinalysis shows pyuria, mild hematuria, and
gram-negative bacteria. Which of the following drugs would
best treat this patient's infection?
A. Ampicillin and gentamicin
B. Erythromycin
C. Gentamicin and vancomycin
D. Tetracycline
 Practice Question

A 35-year-old male undergoes an appendectomy. Several days later,

an abscess has formed at the surgical site. It does not improve with
administration of a cephalosporin, but does respond to nafcillin. The
infecting organism most likely produced an enzyme that would
hydrolyze which bond in the above molecule?
A. A
B. B
C. C
D. D