Antibiotics, J Kinder, Lec Flashcards
what patients do not fall into community acquired pneumonia Tx guidlines
immunocompromised solid organ bone marrow or stem cell transplant chemo long term high corticosteroids congenital or acquire immunodeficiency HIV
What is the evaluation of Illness severity Score
CURB-65 Confusion Uremia (BUN>19) RR >30 BP SBP65)
if CRUB score is 0-1 how do you Tx
if score >3 how do you Tx
0-1: outpatient
>3: admit to ICU
What is minor mriteria for ICU admission
low WBC
low platelets
low core temperature
what are the absolute indications for ICU admission
mechanical ventilation
septic shock
What si required fro Dx CAP
demonstrable infiltrate on CXR
what are common bacteria causing CAP
Spneumonia
H influenza
Moraxella
What bacteria can you not pick up on a gram stain that cause CAP
mycoplasma pneumoniae
chlamydophila pneumoniae
legionella spp
most likley infecting organisms for outpatient
s pneumoniae mycoplasma pneumoniae haemophilus i chalmydophila pneumoniae viral
what are common infecting organisms that we Tx inpatient non-ICU
S pneumoniae M pnuemonia C pnuemonia H influenzae Legionell spp Aspiration Respiratory viruses
What are common infecting organisms for Px that we Tx in ICU
S pneumoniae S aureus Legionella spp Gram neg bacilli H influenzae
What are pathogens that exist with chronic oral steroids or severe underlying bronchopulmonary disease, alcoholism, frequent antibiotic use
enterobacteriae
Pseudomonas aeruginosa
what are common viruses that cause CAP
influenza
RSV
adeno
parainfluenza
not so common viruses that can cause CAP
human metapneumovirus
HSV
Varicella zoster
SARS associated coronavirus
Drug Resistant S penumoniae is seen in what cases
beta lactam use within previous 3 mo!!! age 65 y.o alcoholism immunosuppresive illness or Tx Exposure to child at day care
for a previously healthy Px what is outpatient Tx for CAP
macrolide (azithromycin PO)
Doxy PO
Outpatient recommendations for at risk DRSpneumo
respiratory fluoroquinolones (levofloxacin) Beta lactam PO (high dose amoxicillin, amoxicillin-clavulanate) alternates: (ceftriazone and cefurozime) \+ macrolide!!!
outpatient rec for Px in high rate (>25%)region of macrolid resistant S penumoniae
consider alternatives
What is rec for inpatient non ICU with CAP
Respiratory FQ IV or PO (levofloxacin)
Beta lactam IV (ceftriaxone)+ macrolide IV (azithromycin)
What is rec for inpatient ICU with CAP
B lactam IV (ceftriaxone) + azithromycin IV or Resp FQ (levofloxacin)
What is Tx for patient with beta lactam allergy
FQ
What are risk factors for pseudomonas
structural lung disease
repeated COPD exacerbations
prior antibiotic therapy
Tx for at risk pseudomonas CAP
anti-pseudomonal B lactam IV (piperacillin-tazobactam, cefepime) + cipro or levofloxacin
or B lactam + aminoglycoside (gentamycin and azithromysin)
or B lactam + aminoglycoside & anti-pseudomonal FQ
What are risks for CA-MRSA
end stage renal disease
injection drug abuse
prior influenza
prior antibiotic use (FQ)
Tx for MRSA
vancomycin IV or linezolid
panton-valentine leucocidin nectroizing pneumonia: add clindamycin or use linezolid
When do you switch from IV to oral
imrpoving clinically. hemodynamically stable
tolerating oral meds
normal functioning GI
normal mental status
Describe duration Tx for CAP
minimal 5 days
must be afebrile 48-72 hrs
no more than 1 CAP assoc sign
how long duration does pseudomonas
15 days
When does hospital acquired pneumonia begin
48 hrs after admission
increases length of stay 7-9 days
What is HCAP
health care associated penumonia
common hospital acquired pathofens
P aeruginosa, E coli, K pneumoniae, Acinetobacter Spp, MRSA
what are the oropharyngeal pathogens with hostpial acquired CAP
viridans group strepcocci
coagulase neg staphcocci
neisseria spp
corynebacterium spp
what can lead to pseudomonas R and what drugs is it becoming R to
mutlitple efflux pumps
decreased expression of outer membrane porin channel
piperacillin, ceftazidine, cefepime, imipenem, meropenem, aminoglycosides, FQs
What are the gram neg pathogens that are acquiring R and to what antibiotics
Klebsilla- ampicillin, cephalosporins and aztreonam
Enterobacter- cephalosporins
What does antibiotic carbapenem attack
the plasmid mediated AmpC-type enzymes (ESBL)
What is mech for MRSA
penecillin binding proteins have reduced affinity for B lactam
still R to linezolid, inc R is rare
What is mech behind DRSP
altered penicillin binding protein
still susceptible to vanco and linezolid
Dx for Drug Resistant CAP is what
radiographic infiltrate that is new or progressive
fever, purulent sputum, leukocytosis, decreased O2 sats
What is empiric Tx for early onset HAP
ceftiaxone OR FQ
OR ampicillin
or ertapenem
What are potential pathogens for late onset HAP
P aeruginosa
K pneumoniae
Acinetobacter
MRSA
Tx for late onset HAP
Antipseudomonal cephalosporin or antipseudomonal carbapenem or B lactam + antispeudomonal FQ or aminoglycoside (gentamycin) \+ linezolid or vanco if think MRSA
What is drug of choice for non-resistant S pneumoniae
penicillin G, amoxicillin
What is drug of choice for resistant S pneumoniae
cefotaxime, ceftriaxone, levofloxacin, moxifloxacin, vanco, linezolid
What is drug of choice for H influenze
non B lactamase producing: amoxicillin
B lactamase producing: 2nd or 3rd generation cephalosproin, amoxicillin/cluvulanate
what is drug of choice for Mycoplasma pneumoniae or chlamydophila pneumoniae
Macrolide, tetracycline
What is Drug of choice for legionella
FQ, azithro or doxy
What is drug of choice for eneterboacteriae
3rd or 4th generation cephalosprin, carbapenem (if ESBL producer)
what is drug of choice for pseudomonas
antispeudomonal B lactam + cipro or levo (FQ) or an aminoglycoside
what is drug of choice for anaerobic pathogens like bacteroidesm fusobacterium and peptrostrep
B lactam/B lactamase inhibitor, clindamycin
What is drug of choice for staph aureus
methicillin sensitive: penicillin (nafcillin, oxacillin, dicloxacillin)
methicillin R: vanco or linezolid
adverse effect of clinda
diarrhea
What is drug of choice foe pneumocystic jiroveci
trimethoprim/sulfamethoxazole
Drug of choice for bordetella pertussis
azithromycin, clarithromycin
what is drug of choice for influenza virus
oseltamivir, zanamivir
What is drug of choice for coccidioides spp
no Tx necessary if normal host
otherwhise azoles
Tx for histoplasmosis and blastomycosis
itraconazole
Where can antibiotics target
cell wall synthesis, cell membrane synthesis
synthesis of 30S and 50S ribosomal subunits
nucleic acid metabolism
function of topoisomerases
folate synthesis
How do beta lactams work
covalently bind penicillin binding proteins inhibiting the last transpeptidation step in cell wall synthesis
what leads to beta lactam synthesis
structural differences in PBPs
decreased affinity
drug destruction and inactivation!!
active efflux pumps
adverse effects penicillins
allergic reactions anaphylaxis interstitial nephritis nausea, vomiting, mild to severe diarrhea Pseudomembranous colitis
What are adverse effects cephalosproings
cross reactivity to penicillins
diarrhea
intolerance to alcohol
adverse effects to carbapenems
nausea/vomiting
seizures
HS
MOA vancomycin
binds terminal end of cell wall precursor units
Resistant mech vanco
alteration ot D-Ala D ala target to something else so binds poorly
Adverse effects to vanco
macular skin rash, chills, fever
red man syndrome (histamine release) extreme flushing, tachy and hypotension
ototoxicity, nephrotoxicity
MOA FQ
concentration dependent that binds bacterial DNA gyrase and topoisomerase IV
prevents relaxation of + supercoils
Resistant mech FQ
mutation in genes encoding DNA gyrase or topoisomerase IV
active transport out of cell
adverse effects FQ
GI: nausea, vomiting, abdominal discomfort
CNS: mild HA, dizziness
rash photosensitivity, achilles tendon rupture (don’t give in children)
What antibiotics inhibit 30S subunits
aminoglycosides and tetracyclines
adverse effects aminoglycosides
ototoxicity, nephrotoxicity, NMJ toxicity
adverse effects tetracyclines
GI, superinfecitons with C difficile
photosensitivity, teeth discoloration
do NOT give to peds
What antibiotics inhibit 50S subunits
Macrolides
Clindamycin
Streptogramins
Linezolid
What are adverse effects macrolides
GI, heptotoxicity, arrhythmias
adverse effects clindamycin
diarrhea, C difficile, skin rash
adverse effects streptogramins
infusion pain and phlebitis
adverse effects linezolid
myelosuppression, HA, rash
anemia, thrombocytopenia
do NOT use with serotonin inhibitor usually
How long is incubation for influenza
1-4 days
When is viral shedding influenza
day after Sx 5-10 days after illness onset
Sx influenza
abrubt
fever, myalgia, HA, malaise, non-productive cough, sore throat, rhinitis
When do Sx resolve in influenza
3-7 days uncomplicated
cough and malaise can last >2 weeks
the hemagglutin protein on virus binds what on cell lining
sialic acid
What are the neurominidase inhibitors
oseltamivir PO and zanamivir INH
How do neurominidase inhibitors work
analogs to sialic acid so interfere with release of influenza virus from infected host cell
adverse effects oseltamivir
nausea, vomiting, abdominal pain, HA< fever, diarrhea, neuropsychiatric
approved for children >1 yr
adverse effects zanamivir
cough, bronchospasm, dec pulm function, nasal throat discomfort, not rec in underlying resp disease
children >7 yrs
How does R occur with neuroaminidase inhibitors
point mutation in viral hemagglutinin or neuraminidase surface proteins
Tx use neurominidase inhibitors
influenza prophylaxis, influenza Tx
What Tx influenza A
M2 channel blockers
amantadine PO and rimamtadine PO
how do M2 Ch blocker work
block M2 proton ion channels or virus inhibiting uncoating of viral RNA within host cell
adverse effects M2 ch blockers
GI, CNS dizziness, severe behavioral changes, delirium, agitation seizures from affect on dopamine transmission
How does R to M2 Ch blockers occur
point mutations
What antivirals are used for HSV and VZV
acyclovir (PO and IV and topical)
valacyclovir (PO)
MOA of cyclovirs
3 phosphorylation steps for activation, first via virus specific thymidine kinase.
inhibit DNA synthesis
chain termination following incorporation into viral DNA
What are the cyclovirs used to Tx
genital herpes, varicella, HSV encephalitis, neonatal HSV Tx
adverse effects cyclovirs
nausea, diarrhea, HA
What antivirals are used for CMV
ganiclovir and valganciclovir
Hwo do the ciclovirs work
acyclic guanosine analog that requires activation by triphosphorylation before inhibiting DNA polymerase
uses of the ciclovirs
CMV retinitis and CMV prophylaxis
Adverse effects ciclovirs
myelosuppression, nausea, diarrhea, fever, peripheral neuropathy
what are the fungi of clinical interest
candida albicans, histo capsulatum, crytpto neoformans, coccidioides immitis, aspergillus spp, blastomyces dermatitidis
how do azole antifungals work
inhibit gunal cytocrhome P450 reducing the production of ergosterol
what is ergosterol
cell membrane of fungi instead of cholesterol
use azoles
wide spectrum fungi
what are adverse effects azoles
minor GI upset, abnormalities in liver enymes
major drug interactions of azoles
statins
anti convulsants
warfarin— bleeding!!
adverse effects voriconazole
visual changes and photosensitivity
What is amphotericin B
polyene macrolide antibiotic that binds ergosterol and puts pores in cell membrane
Tx use amphotericin B
broadest epctrum used in life threatening infections
adverse effects amphotericin B
infusion related fever, chills, vomiting, HA and cumulative toxicity in kidneys
What are echinocandins
caspofungin, micagundin
inhibit synthesis B(1-3)glucan which disrupts fungal cell wall
Tx use in echinocandins
candida and aspergillus, only IV
adverse effect echinocandins
minor GI, flushing
