(Detailed) Antibacterials By Sarah E.. General Info What is an empirical therapy? One in which the...

(Detailed) Antibacterials

By Sarah E.

General Info

What is an empirical therapy?• One in which the infecting organism is not knownDo you use broad or narrow spectrum drugs for

this?• broad spectrum (OR combo)What is a definitive therapy?• One in which the infecting organism is known.Do you use broad or narrow spectrum drugs for

this?• narrow spectrum

General Info

Name all antimicrobials that are contraindicated in pregnant women.

• tetracyclines, aminoglycosides, fluorquinolones, sulfonamides, and metronidazole

Do you use bactericidal or bacteriostatic drugs in immunocompromised patients?

• bactericidal

β-lactamsMechanism of action?• bind PBPs and inhibit cell wall synthesisCan be used to treat intracellular organisms?• No. Do not cross membranesBactericidal or bacteriostatic?• bactericidal for ACTIVELY GROWING BACTERIAExceptions?• Only static for Enterococcus sp.Predominant mode of excretion?• kidneysExceptions?• ceftriaxone and anti-Staph penicillins (dicloxacillin- bile)

β-lactams

Mechanisms of resistance?• β-lactamase production• altered PBPs• altered porins (gram negatives)Name three organisms that have altered PBPs.• pneumococci (ie. Streptococcus pneumoniae),

gonococcus, enterococcus• Makes them resistant to most β-lactams!Can these be used to treat Neisseria gonorrhoea?• Only 3rd generation cephalosporins!Can pregnant women take these drugs?• yes!

β-lactams

Name 5 organisms that encode plasmid β-lactamases.

• Haemophilus, E. coli, Neisseria, Salmonella, Klebsiella, Shigella (HEN S(e)KS)

Name 2 organisms that have constitutive chromosomal β-lactamases.

• Bacteroides, MoraxellaName 3 organisms that have inducible or

Extended-Spectrum β-lactamases.• Pseudomonas, Enterobacter, Serratia

β-lactams

Name the 4 categories of β-lactams.• Penicillins, cephalosporins, carbapenems,

monobactamsName 1 non β-lactam cell wall inhibitor• vancomycin

Penicillins

Name the 4 categories of Penicillins• original, anti-staphylococcal, amino-

penicillins, anti-pseudomonalName 3 places these do NOT distribute.• eye, prostate, CNS (unless meninges are

inflamed and leaky!)

Penicillins

Long or short half-lives?• shortWhat three things can lengthen the half-life?• kidney failure, probenecid*, aspirin (inhibit

renal tubular (and CNS!*secretion)Which category of penicillin is NOT affected by

those things?• anti-staphylococcals (eliminated via bile, not

kidneys) (and also ceftriaxone)

Penicillins

Name the major adverse effect of penicillins.• allergies!! Anaphylaxis (severe) or rash (mild)Name an adverse effect of oral penicillins.• GI distress/pseudomembranous colitisWhat can these drugs do to the vagina?• yeast infections! (flora imbalance)What are the toxic effects of these drugs?• seizures (in patients with renal dysfunction or

CNS lesions) and hyperkalemia

The Original Penicillins

Name the “original penicillin” on our list.• Penicillin GWhen do you use the IV form, these days?• treating endocarditis in combo with an aminoglycosideFor which disease is the injectable form the DOC?• PRIMARY SYPHILISWhich form of the original penicillin can be take orally?• penicillin V (acid stable)What do you take penicillin V for?• mild gram (+) cocci infection (eg. GAS “strep throat”)


Are these useful for most Staphylococcus infections?• No (β-lactamases)Intracellular infections?• NoMost gram negatives?• NoStreptococcus pneumoniae?• No (altered PBPs)Spirochetes?• YES (syphilis is caused by the spirochete

Treponema!)


Intracellular Gram negative cocci?• Not really (but some N. meningitidis if you

can get the drug there!)What do you have to take care to do if giving with aminoglycosides?• Administer in separate IV lines

Anti-staphylococcal penicillins

Name the one on our list.• dicloxacillinAre these broad or narrow spectrum?• VERY NARROWWhat kind of organisms do these treat?• Staphylococcus sp. (duh?) with PLASMID

ENCODED β-lactamasesHow are these excreted?• in the bile!

Amino-penicillins

Name the one on our list.• AmoxicillinHow does the spectrum compare to the original penicillins?• Same for gram-pos, but treats more gram negatives• (Broadest spec penicillins)Which gram negatives?• Moraxella, Haemophilus, Salmonella, Shigella, E. coliCan these be take orally?• yep! (amoxicillin causes minimal GI stress)What do you typically prescribe these for?• otitis media, sinusitis, dental infections, etc…

Amino-penicillins

Can you use these to treat H. pylori?• yes, in combo with clarithromycinWhen do you use these prophylactically?• when you’re worried about endocarditis in

high risk patients undergoing proceduresAre these active against organisms with altered

PBPs?• No

Amino-penicillins

Are these inactivated by β-lactamases?• YesName 2 things you can co-administer to prevent this.• clavulanate or tazobactam (β-lactamase

inhibitors)Are amino-penicillins effective against Streptococcus

pneumoniae?• No (because of altered PBPs)Can these drugs treat Listeria meningitis?• yes, if the meninges are inflamed and leaky

Anti-pseudomonal penicillins

Name the one on our list.• piperacillinHow does the spectrum of these drugs compare to penicillin and

amoxacillin?• Less gram(+), more gram (-)Which gram (-)s?• Pseudomonas, Enterobacter, SerratiaAre these inactivated by β-lactamases?• YesWhat can you add to prevent this?• clavulanate or tazobactamAre these combinations effective against Pseudomonas species that

have inducible chromosomal β-lactamases?• No

Penicillins

Name the original penicillin.• Penicillin G (Oral=Penicillin V, IM = benzthine

penicillin G)Anti-staphylococcals?• Dicloxacillin (also not on the list, nafcillin, oxacillin)Aminopenicillins?• Amoxicillin, (and not on the list ampicillin)Anti-pseudomonals?• Piperacillinβ-lactamase inhibitors?• Clavulanate, tazobactam

Cephalosporins

How many generations are there?• 4As generation # increases, resistance to β-lactamases…• IncreasesAs generation # increases, activity on gram-positives…• DecreasesAs generation # increases, activity on gram-negatives…• increases

Cephalosporins

1st generation cephalosporins (on our list)?• Cefazolin, cephalexin2nd generation?• Cefuroxime, cefprozil3rd generation?• Ceftriaxone, cefixime4th generation?• cefepime

Cephalosporins

Are any of these drugs effective against MRSA?• NoEnterococcus sp.?• NoListeria monocytogenes?• NoAre these drugs more active or less active against gram-negative rods than amoxicillin?• More active

Cephalosporins

Can you use these drugs in patients with severe penicillin allergies?

• NoIn patients with mild penicillin allergies?• yesIn pregnant women?• yesAre these drugs broader or narrower in spectrum than penicillins?• BroaderAre oral cephalosporins more or less potent than parenterals?• Less potent

Cephalosporins

Do oral cephalosporins have a broader spectrum than parenteral cephalosporins?

• NoWhich generation achieves therapeutic concentrations in the CNS?• 3rd generationDoes oral administration reach the CNS?• NoName the two drugs in the 3rd generation that are on our list.• ceftriaxone and cefixime

1st Generation Cephalosporins

Name two of these that are on our list.• Cefazolin and cephalexinAre these active (generally) against gram positive cocci?• Yes, including many Staphylcoccus β-lactamases-Name 3 exceptions.• MRSA, Enterococcus, penicillin-resistant

pneumococciAre these drugs active against Neisseria?• nope

1st Generation Cephalosporins

Name the gram-negative rods that these drugs can treat.• Proteus mirabiluis, E. coli, Klebsiella

pneumoniae (PEcK)Name two indications for cefazolin.• Prophylaxis for surgery, anti-staph in mildly

allergic patientsName an indication for cephalexin.• Substitute for oral penicillins (mild infections)

2nd Generation Cephalosporins

Name our 2nd generation cephalosporins.• Cefuroxime, cefprozilDo these have more or less activity against gram-positives than generation 1?• LessName the gram-negatives that these cover.• Haemophilus, Enterbacter, Neisseria, Proteus, E.

coli, Klebsiella, Serratia (HEN PEcKS)Which β-lactmases are these NOT resistant to?• Inducible chromosomal lactamases of

Pseudomonas, Enterobacter, and Serratia

2nd Generation Cephalosporins

Do any of these enter the CNS?• Actually yes. Cefuroxime does, but 3rdGCs are

better for menigitis and pneumoniaWhy are these considered the “lost” generation?• They aren’t often listed of drugs of first choice,

and they are more expensive than 1stGCs as substitutes for oral penicillins

3rd Generation Cephalosporins

Name our 3rd generation cephalosporins.• Ceftriaxone, cefiximeDo these have more or less activity against gram-positives than generation 2?• LessAre these active against bacteria with altered PBPs?• Yes, many of them! (pneumococcus, eg.)Are these active against Streptococcus sp?• Yes! (even though they are generally less potent

against gram-positive cocci than 2ndGCs


Are these more or less active against gram-negatives than 2ndGCs?• More active!Particularly which gram-negatives?• EnterobacteriacieaeWhich β-lactamases are these NOT resistant to?• Inducible chromosomal lactamases of

Enterobacter, Serratia, and PseudomonasHow are these drugs excreted?• Through the urine EXCEPT ceftriaxone


Name two diseases for which this class is the drug of choice.• Meningitis (initial treatment in kids over 3 months

and immuno-competent adults)• GonorrheaFor which kind of bacterial infection (gram+ or gram-) is ceftriaxone a first line drug?• Serious gram-negative infectionsIs ceftriaxone active against Pseudomonas aeruginosa?• Nope.


Should you use these drugs to treat otitis media, respiratory tract infections, or UTIs?• No. There are cheaper drugs that work just as well

(Note: they ARE recommended for otitis media in regions with resistant infections)

Can these drugs treat typhoid fever?• YesEndocarditis?• SometimesCommunity acquired or nosocomial pneumonia• Both when in combination with macrolide or

aminoglycoside respectively

4th Generation Cephalosporins

Name our 4th generation cephalosporins (that are on the list)• Cefepime (there’s only one on our list!)Is this generation resistant to inducible chromosomal β-lactamases?• More than the other generations are What can this treat that 3rd generation cephalosporins can’t?• Pseudomonas, Enterobacter, Serratia, (in

other words, nosocomial gram-neg infections)

Cephalosporins (name recap)


All Cephalosporins

Name the most common adverse effect for all cephalosporins.• Hypersensitivity reactions (identical to

penicillin)Name a side-effect that can occur especially in when these are taken in combination with an aminoglycoside.• Nephrotoxicity

All Cephalosporins

Do these cause “superinfections” more commonly than amoxicillin or clindamycin?• No, but superinfections can still occur

(resistant gram-positives such as C. difficile)Name two side-effects that occur as a result of the method of administration.• Pain with IM, phlebitis with IV

Carbapenems

Name the ones on our list.• Imipenem-cilastatinAgainst which species is this class NOT active?• MRSA, most Enterococcus sp. (this is the

broadest spectrum β-lactam)Is this class resistant to extended spectrum β-lactamases?• Yes! Most of them!Name three genera of bacteria that have these.• Pseudomonas, Enterobacter, Serratia

Carbapenems

Can this class be used to treat Pseudomonas aeruginosa?• Yes, but add gentamicin to reduce resistanceCan this class be used to treat Aceinetobacter?• YesWhen should you use these drugs?• When there are mixed infections and other

drugs can’t be used (ie. Try not to use them)Do these drugs get to the CNS?• Yep!

Carbapenems

Where is are these eliminated?• In the urineWhich part of imipenem-cilastatin is the antibiotic?• ImipenemWhat the heck is the cilastatin?• Inhibits the renal dihydropeptidase that breaks

imipenem into a toxic compound• (note, some other drugs in this class are resistant

to breakdown by that enzyme all by themselves)

Carbapenems

Name 3 adverse reactions.• Nausea and vomiting• Hypersensitivity• seizures in patients with CNS lesions or renal

insufficiencyCan pregnant women take these?• Yes.

Monobactams

Name the one on our list.• AztreonamWhat is the spectrum of this drug?• Gram negative aerobes!! (very specific)Name 4 genera included in this category.• Pseudomonas, Enterobacter, Serratia, HaemophilusWhen should you use this drug?• In patients severely allergic to

penicillins/cephalosporins who have gram-negative aerobe infection

Monobactams

Are there adverse effects?• VERY FEW (phlebitis, skin rash, abnormal liver

test)How are these excreted?• UrineDo these cross-react with allergy to penicillins?• no

Let’s REHASH THE NAMES

Because they all sound the same.

Penicillins

Name the original penicillin.• Penicillin G (Oral=Penicillin V, IM = benzthine

penicillin G)Anti-staphylococcals?• Dicloxacillin (also not on the list, nafcillin, oxacillin)Aminopenicillins?• Amoxicillin, (and ampicillin)Anti-pseudomonals?• Piperacillinβ-lactamase inhibitors?• Clavulanate, tazobactam

Cephalosporins


Other β-lactams

Carbapenems?• Imipenem-cilastatinMonobactams?• aztreonam

β-lactams

Which are NOT excreted in the urine?• Dicloxacillin (and other anti-staph penicillins), and

ceftriaxoneWhich are effective against Pseudomonas aeruginosa?• Piparcillin-tazobactam (unless there are ESBLs),

cefepime (4th GC), carbapenems, monobactamsWhich used usually against Streptococcus sp.?• Penicillin V (mild pharyngitis infections), cephalexin

(1st GCs), cefprozil (2nd GCS—but more expensive), ceftriaxone, or cefixime (if resistant because of altered PBPs, as in S. pneumoniae), or cefepime

β-lactams

Which is the DOC for gonorrhea?• Ceftriaxone or cefixime (3rd GCs)Which is the initial DOC for meningitis?• Ceftriaxone (3rd GC) (immuno-competent and

older than 3 months)Tougher question. WHY is this the initial DOC for meningitis?• Most common bacterial cause in adults are Strep.

pneumoniae, Neisseria meningitidis, and Haemophilus influenzae, and ALL are can be treated with this drug

β-lactams

Which is the DOC for primary syphilis?• Penicillin G (single IM injection)Which does NOT show allergic cross reaction with penicillins?• Monobactams (aztreonam)Which is used as prophylaxis for surgery (in hospitals WITHOUT high rates of MRSA)?• Cefazolin (1st GC)Which are effective on gram-negatives ONLY?• Aztreonam (monobactams)

Glycopeptide cell wall inhibitors

Name the one drug in this class.• Vancomycin!!!What is it’s mechanism of action?• Inhibits crosslinking of peptidoglycans by binding D-

ala-ala, blocks cell wall synthesisBactericidal or bacteriostatic?• BactericidalGram-positives, gram-negatives, or both?• Gram-positives onlyIntracellular, extracellular or both?• Extracellular only

Vancomycin

Can this be used to treat some kinds of meningitis?• Yes, with 3rd GCs. It can cross inflamed meninges.Name one infection for which this is a DOC?• MRSA!! (Especially nosocomial MRSA)Which strains of bacteria have shown resistance?• Enterococci sp.How is vancomycin eliminated?• In the urine

Vancomycin

Name 6 recommendations for using vancomycin1. Treating MRSA2. Serious gram-positive infection in patients with β-

lactam allergies3. ORAL treatment of C. difficile4. Endocarditis prophylaxis in patients with β-lactam

allergies5. Prophylaxis for implantation of device in hospitals

with high rates of MRSA6. Initial empiric treatment of pneumoccocal

meningitis in areas with resistant S. pneumoniae

Vancomycin

Name two relatively common adverse effects.• Hypersensitivity (rashes/anaphylaxis)• “Red-man” or “red-neck” syndrome-due to massive

histamine releaseWhat can you do to stop “red-man” syndrome?• Slow the IV dripName two relatively rare adverse effects.• Ototoxicity and nephrotoxicity (at high plasma levels)Name one other class of antimicrobial that can further increase the risk of these rare affects• aminoglycosides

Last Resort Antibiotics

Name 3 antibiotics of last resort.• Quinupristin/dalfopristin• Linezolid• DaptomycinWhen should you use these?• When you can’t use anything else.• Otherwise never.

Quinupristin/dalfopristin

Are both of these components antibiotics?• Yes. They are streptogramins.Bactericidal or bacteriostatic?• Bacteriostatic individually, synergistically

bactericidalMechanism of action?• Dalfopristin binds 50S ribosomal subunit,

conformation change, enhances quinupristin binding to another 50S site, elongation is blocked


To what other class are these streptogramins related?• MacrolidesDo these streptogramins inhibit CYP450?• Yes. Heads up!What infections are these drugs used to treat?• Vancomycin resistant Enterococci (especially

faecium), Streptococci, and Staphylococci (including MRSA)


Is there resistance to these drugs?• Yes. Quinupristin is cross resistant with

erythromycin and clindamycinName 4 adverse effects• Joint/muscle aches• Phlebitis• Nausea• rash

Linezolid

Bacteriocidal or bacteriostatic?• Bacteriostatic OxazolidinoneMechanism of action?• Inhibits initiation of protein synthesisUsed to treat?• VRE (faecium and faecalis), MRSA, MRSE,

penicillin resistant pneumococci, and S. aureus with intermediate vanc. resistance

Linezolid

Side effects?• myelosuppression (but generally a well

tolerated drug)Take caution when taking which other drugs?• Adrenergic/serotenergic agents because this

acts as MAO inhibitorAny resistance to this drug?• yes. Some has been observed.

Daptomycin

Bactericidal or bacteriostatic?• Bactericidal cyclic lipopeptideMechanism of action?• Theoretical insertion of lipophilic tail into

bacterial membrane, rapid depolarization and ion efflux, arrest of DNA, RNA, and protein synthesis

Side-effects?• High doses= increased CPK, muscle discomfort

and weakness

Protein Synthesis Inhibitors

Name 5 categories of drugs in this class.• aminoglycosides, tetracyclines, macrolides,

clindamycin (a lincosamide), chloramphenicolAre most of these drugs bactericidal or bacteriostatic?• BacteriostaticExceptions?• The aminoglycosides and sometimes

macrolides (concentration dependent)

Aminoglycosides

Name the one on our list.• Gentamicin• (others are amikacin, tobramycin, streptomycin—for TB)Mechanism of action?• Irreversible binding to 30s subunitSpectrum?• Gram-negative aerobes (bacilli)!! Staphylococci, and some

mycobacteriaWhy?• Requires oxygen-dependent transporter to get into cell, and no cell

wall (Streptococci have a different transporter)What drug treats gram-negative aerobes only (similar spectrum to gentamicin)?• Aztreonam (a monobactam)

Aminoglycosides

Name the gram negatives that these treat.• Pseudomonas aeruginosa, EnterobacteriaceaeWhat combo broadens the spectrum?• Combine with a cell wall synthesis inhibitor

(like a β-lactam or vancomycin)Is the therapeutic index of these drugs low or high?• Very low

Aminoglycosides

Name 2 common adverse effects.• Ototoxicity (dose dependent, cumulative use,

potentiation by other ototoxic drugs, irreversible)• Nephrotoxicity (accumulates in and kills renal

tubule cells, reversible, dose dependent)Name 1 rare adverse effect• Curare-like neuromuscular blockade at high

dosesCan pregnant women take these.• No

Aminoglycosides

Are these drugs often used alone?• No. combos reduce toxic effectsName a combo to treat endocarditis.• Gentamicin + penicillinsName a combo to treat septicemia or nosocomial pneumonia.• Gentamicin + 3rd GCName a combo to treat MRSA• Gentamicin + vancomycin

Aminoglycosides

How are these drugs excreted?• In the urineAre these absorbed from the GI tract?• No. They are too polarDo these drugs enter the CNS?• NoThe eye?• NoEukaryotic cells?• No

Aminoglycosides

What is the primary mechanism of resistance?• Inactivating bacterial enzymesHow do Enterococcus sp. resist?• Mutations in 30s binding sitePseudomonas?• Decreased transport into bacteriumDo the aminoglycosides show cross resistance with each other?• Sort of, but not totally. Inactivating enzymes are

identical

Tetracyclines

Name the one on our list.• DoxycyclineBactericidal or bacteriostatic?• BacteriostaticMechanism of Action?• Reversible binding of 30s subunitMost common mechanism of resistance?• Drug efflux2 other mechanisms of resistance?• Modified ribosome binding site, drug modification

Tetracyclines

Do these drugs get into cells?• YesDo these drugs get into the CNS?• NopeAre these drugs broad spectrum?• They used to be, but there’s a lot of resistance nowCan pregnant women take them?• No-interferes with calcium deposition/bone

developmentCan kids take them?• Not under age 8 for the same reason

Doxycycline

Does this drug have a long or short half-life?• long, (once a day dose is ok)Can this be taken orally?• YesDoes food interfere with the absorption?• Generally no, but di and tri-valent cations can chelate

it and prevent absorptionHow is doxycycline excreted?• FecesHow are other tetracyclines excreted?• urine

Tetracyclines

Name 8 diseases that tetracyclines are used to treat.• Lyme disease (spirochetes)• Syphilis (spirochetes)• Mycoplasma pneumonia• Cholera (V. cholerae)• Legionella• Rickettsia• CA-MRSA in patients allergic to TMP-SMXThese are used as prophylaxis for which disease?• Malaria (reasons unknown for why this prevents)

Tetracyclines

Name 4 adverse effects other than the bone/teeth thing.• GI distress• Intestinal/vaginal superinfection• Skin photosensitivity• Vestibular reactions (high doses)

Macrolides

Name the two on our list.• Erythromycin and azithromycinMechanism of action?• Binds 50s subunitBactericidal or bacteriostatic?• Bacteriostatic (cidal if high enough concentration)Name 4 mechanisms of resistance.• Reduced permeability, increased efflux, enzymatic

hydrolysis, modification of ribosomal binding site

Macrolides

Do these drugs show cross resistance with other classes?• YES. Clindamycin and streptogramins (like

Quinupristin!)Can these drugs be taken orally?• YesDoes food interfere with absorption?• YES

Macrolides

Do these get into phagocytes?• Yes (MACs get in MACs)Do these get into the CNS?• NOAre these active against gram-positives?• YesAre these active against gram-negatives?• A fewWhich ones?• Legionella, Bordatella, Haemophilus, Neisseria, H.

pylori

Macrolides

Do these treat intracellular bacteria?•YesName 3.•Chlamydia, Mycoplasma, MycobacteriumDo these treat spirochetes?•yesName 2.•Borrelia, Treponema

Macrolides

For which diseases are macrolides the DOC?•CA-pneumonia (pneumococcus, Mycoplasma, Legionella), Legionnaire’s disease, corynebacterial infections (diphtheria), and chlamydia

Erythromycin v. Azithromycin

Which is better tolerated orally?• AzithromycinHow does erythromycin affect the intestines?• Directly affects motilityWhich has a shorter half-life?• Erythromycin (about 90 minutes)What is the half life of azithromycin?• 2-4 days


Which one is metabolized in the liver?• BothWhich one inhibits P450 oxidation of other drugs?• Erythromycin (Azithromycin does NOT)Which one can’t be taken with digoxin?• ErythromycinWhy?• Kills off intestinal bacteria that inactivate digoxin

and inhibits P-glycoprotein efflux, increases serum levels


Which one accumulates in tissues 10-100 times higher than in serum?• AzithromycinWhat is the advantage of this?• Once-daily dosing and single-dose treatment

of some infectionsWhich infections can be treated with a single dose of Azithromycin?• Chlamydia urethritis or pharygitis


Of the two, which is the better for treating CA-pneumonia?• AzithromycinWhich can be used to treat Mycobacterium avium complex?• AzithromycinWhich drug is more expensive?• Arithromycin

Erythromycin

Name a side-effect associated with IV administration.• PhlebitisName 3 rare side-effects.• Hypersensitivity reaction, hepatitis, reversible

deafnessCan this drug cause seizures and arrythmias?• yes, when taken with other drugs that are

metabolized by P450 (such as anticonvulsants and antihistamines)

Lincosamides

Name the one on our list.• ClindamycinMechanism of action?• Acts at same 50s site as the macrolidesIs this drug absorbed orally?• YesDoes this drug get into the CNS?• NoBactericidal or bacteriostatic?• bacteriostatic

Clindamycin

Does this drug show cross-resistance with other drugs?• Yes. With macrolides.Does this drug get into phagocytes?• Yes.Does this drug penetrate abscesses?• Yes!How is this drug eliminated?• By the liver

Clindamycin

Which gram-positive organisms does this treat?• Strep, staph, pneumococci, anaerobesWhich gram-negative organisms does this treat?• Bacteroides sp. And other anaerobesSeeing a theme?• Anaerobes!Name some organisms that are resistant to clindamycin.• Gram-neg aerobes, C. difficile, enterococci

Clindamycin

When is this used for prophylaxis?• By dentists to prevent endocarditisName two infections in AIDs patients that this treats.• Pneumocystis pneumonia, toxoplasmosisName 2 important side effects.• hypersensitivity rash, diarrhea (10% of all

patients get resistant C. difficile pseudomembranous colitis)

Clindamycin

When is this used for prophylaxis?• By dentists to prevent endocarditisName two infections in AIDs patients that this treats.• Pneumocystis pneumonia, toxoplasmosisName 2 important side effects.• hypersensitivity rash, diarrhea (10% of all patients

get resistant C. difficile pseudomembranous colitis)For what infections is this the DOC?• Anaerobic infections (as well as Metronidazole)and

CA-MRSA (as well as TMP-SMX)

Chloramphenicol

(Yet another drug)Mechanism of action?• Binds 50s at or near where clindamycin doesMechanism of resistance?• Bacterial enzyme production

(chloramphenicol acyl-transferase – CAT)Does this get into the CNS?• Yes!

Chloramphenicol

Is this drug broad or narrow spectrum?• Freakishly broad spectrum (gram+/-,

aerobic/anaerobic, intracellular and not)For which infections is this the DOC?• None. This is never a first choice drug.So when do you use it?• In patients with resistant infections or who can’t

take other drugsName 2 examples.• CF patients with Burkholderia cepacia, and

meningitis in patients with severe penicillin allergy

Chloramphenicol

Name a common adverse effect.• Dose-dependent reversible bone marrow

suppression (due to possible inhibition of mitochondrial protein)

Name a rare side effect (the one that keeps this drug from being used).• Dose-INDEPENDENT aplastic anemia (fatal if

not treated with bone marrow transplant, 1/30,000 patients get this)

Chloramphenicol

What can this cause in infants?• “Gray baby syndrome”How does this work?• Infants can’t conjugate enough of the drug

with glucuronic acid, toxic levels reachedHow is this drug eliminated?• LiverDoes this drug inhibit P450?• Yes

Anti-folates

What’s on our list for these?• Trimethoprim-sulfamethoxazole (TMP-SMX)Are both components antibiotics?• YesWhat is the mechanism of action of TMP?• Inhibits dihydrofolate reductase (and THF

synthesis)What is the mechanism of resistance to TMP?• Reduced permeability or mutant DHFR

Anti-folates

What is the mechanism of action of SMX?• Competes with PABA (as do other

sulfonamides), blocks DHF synthesisWhat is the mechanism of resistance to SMX?• Reduced permeability, overproduction of

PABA, mutant enzyme, ability to use exogenous folate

Are these drugs ever used separately?• Not in the US

Anti-folates

Can pregnant women take these?• NoCan these drugs be taken orally?• YesDo these get into the prostate?• YesDo these get into the CNS?• YesDo these get into the fetus?• yes

Anti-folates

Where are these eliminated?• More than half in urine, some liverAre these active against anaerobes?• NoAerobes?• Typically yesGram-negative cocci?• YesEnterobacteriaceae?• yes

Anti-folates

Are these active against Ps. Aeruginosa?• NoMost strep and staph?• YesExceptions?• S. pyogenes, MRSAAre these active against most enterococci?• no

Anti-folates

For what diseases are these the first-line treatment?• Adult sinusitis, lower UTI, chronic bronchitis,

prostatitis, Pneumocystis pneumonia, CA-MRSA

Name 4 diseases for which this is an alternative treatment.• Shigellosis, traveller’s diarrhea, acute otitis

media, typhoid fever

Anti-folates

Name 3 common adverse effects.• Hypersensitivitym, GI distress, photosensitivityWhat are the rare adverse effects?• Precipitate in urine and form crystals,

hepatotoxicity in patients with G6PDH deficiency!!, blood disorders

What can sulfonamides do to the fetus?• 3rd trimester, can cause kernicterus (bilirubin

encephalopathy)

Anti-folates

Are the side effects ameliorated somewhat if the patient has AIDS?• No. The side effects get worseDo these drugs inhibit P450?• YES and the BIND ALBUMIN (a double

whammy)

Fluoroquinolones

What’s on our list for these?• CiprofloxacinBactericidal or bacteriostatic?• BactericidalMechanism of action?• Nucleic acid synthesis inhibitor, blocks topoisomeraseElimination?• Kidney in same manner as penicillinsName 2 chemicals that slow excretion• Probenecid, aspirin

Ciprofloxacin

Mechanisms of resistance?• Decreased permeability or mutant

topoisomeraseBroad or narrow spectrum?• Very broadActive against aerobes, anaerobes, or both?• Pretty much just aerobesWho else is just aerobes?• Aminoglycosides!

Ciprofloxacin

Is this drug well distributed?• YesTo where?• Prostate, bone, urine, macrophages, PMNsDoes this drug treat gram-positives?• SomeExceptions?• MRSA, enterococci, variable against

streptococci

Ciprofloxacin

Does this drug treat gram-negatives?• Yes. The AEROBIC onesIntracellular organisms?• SomeWhich ones?• Legionella, Mycoplasma, BrucellaName the major clinical use.• Upper and lower respiratory infections

Ciprofloxacin

Name some other clinical uses.• Traveler’s diarrhea, osteomyelitis, prostatitis,

resitant-TB, MACName two examples where this drug is used prophylactically.• Menigitis and inhalation anthrax in

neutropenic patientsName two organisms which are becoming more and more resistant.• S. pneumoniae and Ps. aeruginosa

Fluoroquinolones

Can pregnant women take these?• No. No pregnant women or kids under 18Why not?• Drug damages developing cartilage, leading to

arthropathyName a few other adverse effects.• GI distress, headaches, dizziness, skin rashes,

abnormal LFTs.• Reports of possible tendon rupture???

Fluoroquinolones

Can you use antacids or mineral supplements when taking these orally?• No. Chelation occurs and the drug becomes less

bioavailableWhat other drugs chelate in the digestive tract?• TetracyclinesDo these inhibit P450 enzymes?• yes, possiblyWhat happens when you take these with NSAIDS or theophylline?• Increased risk of seizures

Metronidazole

Mechanism of action?• Prodrug, converted to active form via a

nitroreductase, binds DNASpectrum?• Anaerobes only! (and some protozoa)…they

have the nitroreductaseWhich ones in particular?• Bacteroides, Clostridium, Trichomonas,

Giardia, Entamoeba

Metronidazole

For which diseases is this the DOC?• Pseudomembranous colitis from C. difficileWhat’s the 2nd choice for C. difficile?• Oral vancomycinName a few other diseases that Metronidazole can treat.• Bacterial vaginosis, abdominal and pelvic

infections, gas gangrene, tetanus, with TMP-SMX for diverticulitis, and for Bacteroides brain abscesses

Metronidazole

Name 3 common adverse effects.• Nausea, dry mouth, taste alterationName a rare side effect.• Peripheral neuropathy (STOP DRUG)Is this drug mutagenic?• In bacteria and rodents, but no human dataCan pregnant women take this?• Not during 1st trimester, avoid during whole

pregnancy if possible

Metronidazole

Does this drug inhibit P450?• YesDo other drugs affect this drug’s half-life?• Yes. Ones that affect P450What can happen when this is taken with disulfiram or ethanol?• Acute psychosis

Anti-mycobacterial drugs

Name 4 reasons that mycobacterial infections are hard to treat.1. Lipid rich cell wall is impermeable to most

drugs (β-lactams definitely won’t work)2. Primarily intracellular3. Slow growing/dormant4. Notorious for resistance

Anti-tuberculosis drugs

Name 5 first-line drugs to treat TB infections1. Isoniazid2. Rifampin3. Pyrazinamide4. Ethambutol5. Streptomycin


Name 2 other drug CLASSES that can be used as 2nd line treatment (note these are not the ONLY other classes that can be used.)• Aminoglycosides (such as amikacin),

fluoroquinolones (such as ciprofloxacin)


Describe the CDC recommended regimen for TB therapy (for active disease).1. Start on 4 first-line drugs (INH, rifampin, PZA,

ethambutol) for 2 months2. When you find out susceptibilities, eliminate

ethambutol if susceptible to INH and rifampin3. Continue INH, rifampin, and PZA for 2 more months4. Eliminate PZA because it is most active on

extracellular organisms5. Continue with INH and rifampin for 4 more months


Wow.How many months was that?• 8! (And that’s for the non-fancy susceptible

TB!)Name 3 reasons to deviate from this regimen.1. TB infection is resistant2. Patient can’t tolerate 1st line drugs3. Patient is already taking drugs that have

significant interactions with rifampin (we’ll get to this)

Isoniazid (aka INH)

MOA?• Inhibits synthesis of mycolic acids (pro-drug

converted to active drug by bacterial enzyme)Resistance?• One mutation away!Is this drug potent against TB?• It is the most potent anti-TB agent we haveCan you use it alone?• Prophylaxis only. Never to treat active disease

Isoniazid (aka INH)

Name 3 relatively common adverse reactions• Allergy• Hepatitis (stop drug if jaundice!)• Peripheral neuropathyHow can you prevent the neuropathy?• B6 supplementationWhat’s the name of B6? (for a bonus)• Pyridoxine!

Isoniazid (aka INH)

Name 2 rare adverse effects.• Systemic lupus erythematosus• CNS toxicity-memory loss, psychosis, seizures

(reverse with B6)Does this drug inhibit P450?• yes

Rifampin

MOA?• Binds RNA polymerase, blocks RNA sythesisResistance?• Mutation of RNA pol, can occur quicklyCan you use this drug alone?• Prophylaxis only. Not to treat.Is this drug absorbed orally?• YesWhere does this drug distribute?• Mostly everywhere (CNS, phagocytes)

Rifampin

How is this drug eliminated?• Metabolized in liver, excreted in bileIs this drug active only against TB?• No. Active against gram-pos and gram-neg

cocci, chlamydia, some enteric bacteria, other mycobacteria

For what is this a DOC?• Neisseria meningitidis and H. influenzae

prophylaxis

Rifampin

Other uses/combos:Leprosy:• Rifampin+dapsone +/- clofazimineLegionella:• Rifampin + erythromycinM. kansasii:• Rifampin +INHMRSA:• Rifampin+vancomycin+gentamicinS. pneumoniae (resistant strain):• Rifampin +vancomycin

Rifampin

Name 3 adverse effects.1. Harmless orange color to body fluids2. Flulike symptoms3. Jaundice (can be FATAL)Does this drug inhibit P450 metabolism.• No! It induces it!! Decreases ½ life of other

drugs• This includes some anti-retrovirals, so HIV

patients with TB should take rifabutin instead of rifampin

Ethambutol

MOA?• Inhibits mycobacterial cell wall sythesis and

enhances actions of rifampin/other lipophilic drugs

Elimination?• 50% in urineDoes this drug get in the CNS?• Only when meninges are inflamed.Clinical use?• Only in combo therapy for TB

Ethambutol

2 Adverse effects?• Reversible visual disturbances (loss of acuity

and red/green colorblindness)• Hyperuricemia/gout

Pyrazinamide (aka PZA)

MOA?• UnknownSpectrum?• Active only against M. tuberculosisName 2 clinical uses.• With ciprofloxacin, resistant TB prophylaxis• With INH, rifampin, ethambutal for TB

treatment

Pyrazinamide (aka PZA)

Name 2 adverse effects.1. Hyperuricemia (occurs in most patients, can

cause gout)2. Hepatotoxicity (requires periodic liver

function tests

Streptomycin

MOA?• It’s an aminoglycoside (the original!), so

irreversible 30S bindingGets into CNS?• NoGets into cells?• No! Useful for extracellular TB only!Used clinically for?• Combo therapy for very serious TB infection

Streptomycin

Adverse effects?• Ototoxic and nephrotoxic (like other

aminoglycosides)

Anti-leprosy drugs

Name 3.1. Dapsone2. Clofazimine3. Rifampin

Dapsone

MOA?• antifolate—related to sulfonamidesAbsorbed by GI?• YesDistribution?• Very well distributedElimination?• Bile and urine

Dapsone

Name 2 clinical uses.• Pneumocystis pneumonia prophylaxis in AIDS

patients• Combo with clofazimine and rifampin for

leprosy1 common adverse effect?• Allergy1 rare adverse effect?• Hemolysis, especially in patients with G6PDH

deficiency

Clofazimine

MOA?• A dye that binds DNACan be taken orally?• YesWhere does this drug accumulate?• Reticuloendothelial cells and skinAdverse effects?• Skin discoloration (reddish to darkish brown)

Clofazimine

2 good things about this drug other than it’s antibiotic effect?• Anti-inflammatory (could also be a bad thing)

and prevention of erythema nodosum leprosum

Clinical use?• With dapsone and rifampin for leprosy• Weak activity against M. avium

Atypical Mycobacterial infections

Most common cause?• Mycobacterium aviumIs normal treatment for TB effective for this?• No.Recommended treatment?• Azithromycin or clarithromycin plus

ethambutol +/- cipro or rifabutin• Use azithro, clarithro or rifabutin as

monotherapy prophylaxis for AIDS patients with low CD4 counts

(Detailed) Antibacterials By Sarah E.. General Info What is an empirical therapy? One in which the...

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