1 DNA disruptors (antibacterial therapies)

what are the fluoroquinolones

- cipro (ciprofloxacin); IV, PO, otic, ophthalmic

- levaquin (levofloxacin); IV, PO, ophthalmic, inhalation

- avelox (moxifloxacin); IV, PO, ophthalmic

- baxdela (delafloxacin); IV, PO

- ofloxacin

when do we use fluoroquinolones

- urinary tract infections (EXCEPT moxi); not for just simple cystitis

- respiratory infections (levo & moxi)

- GI infections (moxi)

- moxi: mild intra-abdominal infections

ciprofloxacin coverage

- pseudomonas aeruginosa **best

- atypicals

- weak Strep pneumoniae coverage

- not usu used for Staph coverage

levofloxacin coverage

not usu used for Staph coverage

- pseudomonas aeruginosa

- strep pneumo (RF)

- atypicals

moxifloxacin coverage

not usu used for Staph coverage

- Strep pneumo (RF)

- anaerobes

- atypicals

NO pseudomonas

baxdela (delafloxacin) coverage

used for diabetic foot ulcers

broadest spectrum

- pseudomonas

- anearobes

- strep pneumo

- MRSA

MOA of fluoroquinolones

- inhibits DNA gyrase: better for gram - / PSA

- topoisomerase IV: better or gram +/ strep pneumo

which MOA of fluoroquinolones is more helpful for gram negatives

- inhibition of DNA gyrase

- ciprofloxacin has a higher affinity for DNA gyrase (does NOT treat strep pneumo)

which MOA of fluoroquinolones is more helpful for gram positives

- inhibition of topoisomerase IV

- moxifloxacin has a higher affinity for topoisomerase IV (does NOT treat pseudomonas)

fluoroquinolones have ___ bioavailability

high

which fluoroquinolones will NOT treat a UTI? why?

- moxifloxacin

- bc it does NOT concentrate in the urine

absorption of fluoroquinolones is decreased when taken with ____

aluminum

zinc

Mg

Fe

Ca++

D -- D interactions with fluoroquinolones

- other QT prolonging drugs

- CYP P450 system (warfarin, theophylline**Esp cipro)

adverse effects of fluoroquinolones

MANY!! rlly not first line

- N/V/D/HA/dizzy

- hypo & hyperglycemic

- photoxicity (sun protection)

- hepatotoxicity (monitor LFTs)

- C. diff

- QT prolong

- hemolytic anemias in G6PD pt

BBW with fluoroquinolones

- tendinitis/ tendon rupture (BBW)

- peripheral neuropathy

- CNS effects

- exacerbates mm. weakness in MG pt

do NOT use fluoroquinolones in ____

- preg

- breast feeding

- pediatric patients

what are the sulfa / sulfa combo drugs

- bactrim (sulfamethoxazole / trimethoprim)

- dapsone

spectrum of activity for sulfa / sulfa combo drugs

- broad spectrum

- gram + (including MRSA)

- gram - (including strenotrophomonas & legionella & pneumocystis jirovecii)

**NO strep coverage

when do we use sulfa / sulfa combo drugs

- bactrim: PCP PNA, strenotrophomonas

- dapsone: leprosy

MOA of sulfamethoxazole

mimics PABA --> inhibition of dihydropteroate synthase

MOA of trimethoprim

its a structural analog of dihydrofolate --> inhibits dihydrofolate reductase

CI of sulfa / sulfa combo drugs

severe hepatic failure

D--D with sulfa / sulfa combo drugs

- warfarin

- phenytoin

- methotrexate

adverse effects of sulfa / sulfa combo drugs

- common: N/V

- hyperK+

- hematologic disturbances (megaloblastic anemia, leukopenia, thrombocytopenia)

- crystalluria

- rashes (SJS, TENs)

- kernicterus

pearls with sulfa / sulfa combo drugs

- patients need to be hydrated (oral form must be administered w at least 8oz H2O

- do not use w patients w G6PD deficiency --> hemolytic anemia

- do not use in kids < 2 & preg women

what are the nitroimidazoles

flagyl, metrogel (metronidazole)

spectrum of activity of metronidazole

- anaerobic gram -

when to use metronidazole

- PO/IV: intra abdominal infections, BV, trichomoniasis

- topical: bacterial vaginosis, rosacea, trichomoniasis

MOA of metronidazole

- nitro group has to be "reduced" to be activated... once it is --> forms free radicals --> breaks up DNA of bacteria --> cell death

D--D with metronidazole

- disulfiram-like rxn when taken with alcohol

** medical myth but could be on exams

adverse effects of metronidazole

- common: N/V, epigastric discomfort

- unpleasant metallic taste

- furring of tongue

- peripheral neuropathy

- carcinogenic (BBW)

what are the nitrofurans

- macrobid, macrodantin (nitrofurantoin)

spectrum of activity of nitrofurans

- aerobic gram +: enterococcus & staph saprophyticus

- aerobic gram -

when do we use nitrofurans

- only cystitis (lower UTIs)

** do NOT use for upper UTIs

MOA of nitrofurans

- bacteria enzymatically reduce NO2 group to active agent that inhibits bacterial enzymes & damages their DNA

adverse effects of nitrofurans

- common: GI upset

- pneumonitis or fibrosis

- peripheral neuropathy

- hepatic dysfunction

fidaxomicin

- dificid (fidaxomicin)

spectrum of activity of fidaxomicin

- NARROW: C. diff (gram + anaerobe)

** we usually use Vanc first, just fidaxomicin is $$$

MOA of fidaxomicin

- acts on RNA polymerase --> bacterial transcription disruption --> protein synthesis termination --> cell death

adverse effects of fidaxomicin

- cross reactivity w macrolides

- common: N/V/abd pain

- hematologic disturbances: anemia, neutropenia

what are the rifamycins

- rifadin (rifampin)

- mycobutin (rifabutin)

- priftin (rifapentine)

- xifaxan (rifaximin)

spectrum of activity of rifamycins

- staph (MRSA), mycobacteria

- rifaximin: meningitis prophylaxis for salmonella & campylobacter

when to use rifamycins

- rifampin/ rifabutin/ rifapentine: mycobacteirum (MAC)

- rifampin: staph infections, prophylaxis for pt exposed to H. influenzae or N. meningitidis meningitis

- rifaximin: travelers diarrhea

MOA of rifamycins

- work by inhibition of RNA polymerase

- resistance develops easily to these agents

adverse effects of rifamycins

- common: N/V/rash

- hepatic failure (caution w alcoholics!! no alc on med)