Pharm: Antibacterials (v. 2)

natural penicillin

+: strep (DOC), entero

-: neisseria (gonorrhea, meningitis), syphilis (DOC)

se: GI

not effective for mycobacteria, protozoa, fungi, and viruses

aminopenicillin

Definition:Amoxicillin (PO).
Coverage:

+: Strep, Enterococcus (DOC)

-: E. coli, Proteus, H. influenzae.
Notes: Can cause rash and GI upset.

penicillinase-resistant penicillin

Definition: Dicloxacillin (PO), Nafcillin and Oxacillin (IV).
Coverage:

+: Staph/MRSA (DOC), Strep

-: none

anaerobes: N
SE:

• Oxacillin increases LFTs

• interacts with warfarin

anti-pseudomonal penicillin

IV ONLY: Piperacillin (more potent)
+: Strep, Enterococcus

-: E. coli, Klebsiella, Proteus, H. influenzae, plus Pseudomonas.
SE: interstitial nephritis, seizures (high dosage)

monobactams

IV/inhalation: aztreonam (IV common)

+ and anaerobes: N

-: e coli, klebsiella, proteus, influenza, catarrhalis, pseudomonas

does not have extra chain fused to it so cross sensitivity in low. can be used for UTI

SE: renal function

use in pts with PCN allergy including IGE reactions

BUT watch out for allergy to cefazidime

carbapenems (DIMME)

IV: meropenems, ertapenem (E and M used most often)

+: staph, strep, (enterococcus only imipenem)

-: e coli, klebsiella, proteus, influenza, catarrhalis, pseudomonas + hospital acquired (ertapenem does not cover pseudomonas)

anaerobes: bacteroides (all DIME)

SE: headache, allergic reaction, GI, seizures (meropenem have lowest incidence), hypotension

info:

• imipenem coupled with cilastatin to protect it from metabolism from renal dehydropeptidase

• drug interaction: valproic acid (used for seizures)

Type I allergy to PCN and need to give PCN: titrate and slowly work your way up OR give full dose in supervised setting

beta-lactamase inhibitors

Definition & Combinations:

• Clavulanic acid (PO) – combined with Amoxicillin (Augmentin)*

• Sulbactam (IV) – Ampicillin-sulbactam (Unasyn)*

• Tazobactam – Piperacillin-tazobactam (Zosyn)*

• Meropenem-vaborbactam (IV)

  NO staph or atypicals
  info:

  • Protects partner drug from beta-lactamase (most successful when they bind to beta lactamase drug irreversibly);

(60, 30, 15 for renal function)

first-generation cephalosporins (lexi plays the zolin but wants no one to ENTERo)

broad spectrum antibiotics, name is from fungus where they’re derived

Definition: Cefazolin (IV), Cephalexin (PO).
+: staph (most active), strep

-: e coli, klebsiella, proteus

NO ENTERO

SE: allergic reaction, GI upset, vaginal yeast overgrowth

second-generation cepharlosporins (think axolotl, fox, and titan = creatures OR think fake, fox, fur, pro, treats)

groups: cefaclor (PO), cefuroxime (IV), *cefuroxime axetil**,cefprozil (PO), cephamycin (cefotetan [IV] and cefoxitin [IV])

*Fake → Cefaclor (PO)

Fox → Cefoxitin (IV) (a cephamycin)

Fur → Cefuroxime (IV) and Cefuroxime axetil (PO)

Pro → Cefprozil (PO)

Treats → Cefotetan (IV) (another cephamycin)

+: staph (less than 1st gen)

- : ecoli, klebsiella, proteus, flu, catarrhalis (same from 1st gen, but add respiratory, since animals gotta breathe)

NO ENTERO

anaerobes: cefotetan and cefoxitin

cefaclor: serum like sickness (rash, arthritis, fever)

cefotetan: disulfiram like reaction (MTT side chain)

cefuroxime: nephrotoxicity

cefuroxime axetil: crosses BBB

SE: allergic reaction, GI upset, vaginal yeast overgrowth

less common: hematologic (pancytopenia), hepatic (inc in LFT)

third generation cephalosporins (PO = “fix” “dinir” and “pod”. IV is 3t’s = “tax, taz, and tri”

Definition: Cefixime (PO), Cefotaxime (IV), Cefpodoxime proxetil (PO), Ceftazidime, Ceftriaxone (IV), Cefdinir (PO) (know all of them)

+: staph and strep NO ENTERO

-: ecoli, klebsiella, proteus, flu, catarrhalis (maintain 2nd generation, + extras!)

pseudomonas (ceftazidime)

gonorrhea (ceftriaxone)

(can give to someone with PCN allergy)

notes:

• cross to BBB

• cefriaxone and cefotaxime can go into CSF

• cefdinir: red stools (if using lots FeSo4. can dec cefdinir concentration)

• ceftriaxone: pseudo biliary lithiasis

• cefpodoxime proxetil: space antacids/H2 antagonists/PPI by 2 hours

SE: allergic reaction, GI upset, vaginal yeast overgrowth

less common: hematologic (pancytopenia), hepatic (inc in LFT)

fourth-generation cephalosporin

cefepime (IV)

+: staph, strep NO ENTERO

-: all pseudonomas

neurotoxicity with cefepime

SE: allergic reaction, GI upset, vaginal yeast overgrowth

fifth generation cephalosporin (imagine STAR and 5th generation = olddddd = fossil)

Definition: Ceftaroline fosamil (IV). NO ENTERO
Coverage: only one that treats MRSA.

SE: allergic reaction, GI upset, vaginal yeast overgrowth

less common: hematologic (pancytopenia), hepatic (inc in LFT)

as you go up the generations, you have less staph and more gram - coverage

cephalosporin and beta-lactamase inhibitor (think tolo tazo?)

IV: Ceftolozane + Tazobactam (Zerbaxa).

+: strep

-: ecoli, klebisella, proteus, ESBL (extended spectrum beta-lactamase producers), pseudonomas

anaerobes: bacteroides

glycopeptides

bactericidal

IV/PO: vancomycin

PO: vancomycin used for C.diff ONLY

**+: staph including MRSA/MRSE, strep, entero

-: none

anaerobes: c.diff for PO only**

SE:

• red man syndrome (due to infusing too QUICKLY. rel to histamine release, pruritus, tingling, flushing of upper body. should infuse 1g over 1 hr)

• nephrotoxicity with aminoglycosides

• ototoxicity (hearing issues)

serum peak and trough levels

• peak: 1 hour after dose (peak too high = lower dose or extend interval)

• trough: 30 mins prior to next injection (too low = inc dose or make intervals closer together)

fosfomycin tromethamine (monurol)

bactericidal

PO only

• indicated for uncomplicated UTis (e coli or e faecalis)

+: staph, entero

-: e coli, klebsiella, proteus, ESBL, CRE

SE: GI + HA

not used for treatment of pyelonephritis. can be used in pregnancy***

low resistance potential

polymyxins

concentration dependent. bactericidal

drug: polmyxin B and E

+: NONE

-: ecoli, klebsiella, pseudonomas

resistant: acinebacter, CPE

anaerobes: none

SE: nephrotoxic → acute tubular necrosis

aminoglycosides (“n/icor gas”)

concentration dependent, **bactericidal**

nebcin, Gentamycin, amikacin, streptomycin for IV

IV: nebcin (tobramycin), gentamycin, amikacin, streptomycin (last 2 important but not as much as the first 2)

PO: inhaled nebcin= tobi (inhaled-tobramycin)

+: synergy. staph, strep, entero

-: e coli, klebsiella, proteus, influenza, catarrhalis, pseudomonas

anaerobes: N
SE:

• nephrotoxicity (reversible. acute tubular necrosis)

• ototoxicity (irreversible)

small margin of safety/narrow therapeutic window

macrolides (protein synthesis inhibitors)

concentration-dependent for bactericidal/static

IV/PO: erythromycin (least coverage and binds to protein the most = not great), azithromycin (most gram - coverage)

**PO: clarithromycin (most gram + coverage)**

-: flu (not erythromycin)

SE:

• cholestatic jaundice

• exacerbation in myasthenia gravis symptoms

• e: GI and prolongation of QT intervals

• CYP inhibitors: prodrugs will not become active. erythromycin and clarithromycin

Info:

• can be used if pt has PCN allergy (b/c similar spectrum of activity)

• azithromycin (longest half life) and clarithromycin (best bioavailability)

lincosamides (protein synthesis inhibitors)

concentration-INDEPENDENT. bactericidal/static based on concentration (cidal at higher conc)

**IV/PO: clindamycin**

anaerobes: propionibacterium

inhibits toxin release: staph and strep

SE: c-diff (more common with clindamycin -abdominal pain, diarrhea), esophageal ulcerations

clindamysin = c.diff

tetracyclines (protein synthesis inhibitors) (DMT = 4 words = tetra?)

bacteriostatic, concentration dep

IV/PO (long acting): doxycycline, minocycline

PO: tetracycline (short acting)

atyicals: syphilis

SE:

• skin allergy

• photosensitivity (doxy)

• disclorations/depression of skeletal growth

• DO NOT GIVE in pregnant women and children under 8-12 years old

• pregnant women: last trimester → discoloration of teeth. first trimester → birth defects and discoloration of teeth

• GI distress (like esophageal ulcerations, nausea → take with water)

Info

• minocycline adverse reactions: bluish, gray nail, skin, and sclera pigment

oxazolidinones (protein synthesis inhibitors)

time dependent, bacteristatic

IV/PO: linezoid, tedizolid (less likely to have drug interactions)

only gram +

SE:

• linezolid: diarrhea, headache, and nausea

Info:

• serotonin syndrome: confusion, tachypnea, muscle twitching, fever, sweating → CNS toxicity

  • SSRI and SNRI (antidepressants, implicated in serotonin syndrome)

    • serotonergic psych meds should be stopped 2 weeks before linezolid treatment. prozac has long half life, should stop 5 weeks in advance

fluoroquinolones (protein synthesis inhibitors) (CLMO, carly loves me o!)

concentration dependent. bactericidal.

IV/PO: Ciprofloxacin (best empiric therapy for UTIs), levofloxacin, moxifloxacin,
PO: ofloxacin

+: Strep (but do NOT use cipro)

anaerobes: moxifloxin ONLY, bacteroides. MOXI also cannot be used for UTIs

SE:

• CNS: confusion, headache

• tendinitis, tendon rupture/muskuloskeletal

• prolongation of QT interval (MOXI)

• photosensitivity (cipro)

• GI: nausea, abdominal discomfort, vomiting, diarrhea

nitrofurantoin (protein synthesis inhibitors) think nitro = big = macro

bactericidal in urine only. first line of therapy for pregnant women w/ UTI. used as urinary tract antiseptics

Definition:
PO: Macrodantin

PO: Macrobid

MOA: inhibits DNA synthesis
Notes: GI side effects (nausea and vomiting). “Beer’s criteria”: avoid if CrCl <30 for long-term suppression of bacteria.

• may have irreversible pulmonary fibrosis as overall symptom

NOT for systemic infections or pyelonephritis (so if UTI moves to kidney, it won’t work).

methenamine (protein synthesis inhibitors)

(prophylaxis only), NO treating acute infection

PO: Methenamine hippurate, mandelate.
Coverage: Prophylactic = produces formaldehyde in urine

formaldehyde: covers all urinary pathogens.
Notes: GI → intestinal distress

Risk of crystalluria when combined with sulfonamides.

sulfonamides (eg, bactrim) (protein synthesis inhibitors)

Definition:
IV/PO: Trimethoprim + Sulfamethoxazole (Bactrim);. WITH TMP (trimethoprim) = bactericidal, not with TMP = bacteriostatic. CONCENTRATION DEPENDENT.

PO: Sulfadiazine (+cream), Sulfisoxazole (usually combined with erythromycin)

Coverage:
GRAM+: Staph (MRSA), Strep (not good for Group A strep [s. pyogenes]),
GRAM -: e. coli, klebsiella, proteus, influenza, catarrhalis

(not good with anaerobes)

Notes: GI upset, hypersensitivity (Stevens-Johnson syndrome), crystalluria (requires hydration), warfarin interaction, photoTOXICITY = TMP

Nitroimidazole (protein synthesis inhibitors)

IV/PO: Metronidazole (PRODRUG)

NO + or -.
Anaerobes: including Bacteroides, protozoa, bacterial vaginosis (Gardnerella), C. diff.
Notes: Disulfiram-like reaction, urine discoloration, peripheral neuropathy, warfarin interaction.

antacids/h2r antagonists/PPI

can decrease absorption of

1. cefpodoxime proxetil (2 hrs to avoid this)

2. cefuroxime axetil (2 hrs)

3. cefaclor (1 hr)

4. cefdinir (2 hr)

probenecid

may increase serum levels of cephalosporins

cephalosporins

may inc anticoagulation effects of warfarin

alcohol

when combined with cefotetan → can result in disulfiram-like effects (even a small amt of ___ will start this)

aminoglycosides

when combined with cefuroxime → may result in nephrotoxicity

iron

interferes with absorption of cefdinir (2 hours)

macrolides comparison

options: clarithromycin, erythromycin, azithromycin

staph: C, E, A

strep: C E A (resistance)

flu: A C E

Atypicals: all “meh”

resistance is due to overuse of Z-paks

macrolides

• erythromycin, clarithromycin

INHIBITION of cytochrome p450 3A4

• examples of what would be inhibited by erythromycin and clarithromycin: phenytoin, tacrolimus, colchicine, simvastatin, lovastatin, atorvastatin, etc

lyme disease

• caused by borrelia burgdorferi. transmitted by bite of infected ticks

• > results in skin lesions, headache and fever, arthritis

• DOXYcycline preferred

antacids (tetracycline drug interactions

deoxycycline, minocycline, and tetracycline: take doxy 1-2 hrs before/6 hrs after antacids EXCEPT IN TETRA IT DEC ABSORPTION BY 90%

calcium

deoxycycline + minocycline : not affected by milk

tetracycline: dec absorption by 50-80% when taking with milk

iron

deoxycycline: give 3 hrs before or 2 hours after doxy dose, dec concentration by 80-90%

minocycline: give 3 hrs before or 2 hrs after mino dose

tetracycline: give 3 hrs before or 2 hours after, DEC concentration by 40-50%

serotonin syndrome

• mental/cognitive and behavioral

  • confusion, hyperactivity, memory problems

• autonomic symptoms

  • fever, sweating, tachy

• neurologic symptoms

  • muscle twitching, tremors, chills

inhibitors of folate synthesis

silver sulfadiazine

sulfasalazine

fluoroquinolones

avoid in pts with

• acute sinusitis

• acute bronchitis

• uncomplicated UTIs

elderly: exercise caution, not contraindicated

pregnancy and breastfeeding: contraindictated

children: contraindicated

myasthenia gravis: not contraindicated, exercise caution

for QTC prolongation the best is moxi > levo > cipro

cipro

drug of choice for anythrax (fluoroquinolones)

cipro and levo

(floxacin) UTI (fluoroquinolones)

moxi

(floxacin) anaerobic infections (fluoroquinolones)

levo

(floxacin) most effective in treating infections unresponsive to b-lactam antibiotics.

cipro not drug of choice for resistant respiratory infection because it’s weak against pneumoniae

____ and moxifloxacin are known as “respiratory fluoroquinolones” (fluoroquinolones)

cipro

(floxacin) good in GI infections (fluoroquinolones)