antimicrobial stewardship, sti, covid, global health Flashcards
antimicrobial stewardship
coordinated interventions designed to improve and measure the appropriate use of antibiotic agents by promoting the selection of the optimal drug regimen including dosing, duration of therapy, and route of administration
goals of antimicrobial stewardship
- optimize clinical outcomes
- minimize toxicity and AEs
- reduce infection costs
- prevent resistance
what is the biggest reason we need stewardship?
resistance
two ways resistance spread?
animals
humans after antibiotic course
resistant pathogens of threat
urgent:
1) carbapenem-resistant acinetobacter
2) carbapenem-resistant enterobacterales
- klebsiella (KPC), enterobacter
serious:
3) ESBL (extended-spectrum beta lactamase) producing enterbacerales
- klebsiella, enterobacter
4) vancomycin-resistant enterococcus (VRE)
5) multidrug resistant pseudomonas aeruginosa
6) methicillin resistant staph aureus (MRSA)
concerning:
does bacterial colonization mean we treat?
not always –> colonization does not mean infection
*catheters will always grow bacteria!!!
problems with antibacterial prescribing
- low threshold to prescribe
- broad spectrum empiric therapy never deescalated
- suboptimal regimens used –> want narrowest spectrum!!
consequences of inappropriate antibiotic therapy
patient:
- inadequate treatment
- AEs
- allergic reactions
- superinfections
- resistance
- selection for problem pathogens like c diff
society:
- resistance
- collateral damage (ruin natural biome –> c diff)
- inc healthcare costs
benefits of antimicrobial stewardship
- improve patient outcomes
- dec AEs
- minimize resistance/maximize susceptibility
- resource optimization
- reduce healthcare cost without dec quality of care
UTI treatment requirements
NOT if bacteria in urine but not symptoms (asymptomatic bacteriuria)
UNLESS
1) pregnant
2) urologic procedure (inc risk goes into blood during procedure)
UTI symptoms that indicate treatment
ONLY
1) dysuria (painful/burning urination)
2) inc frequency
3) inc urgency
4) superpubic pain
IV MRSA options
- vancomycin
- linezolid
- daptomycin
PO pseudomonas options
ONLY fluoroquinolones
- ciprofloxacin
- levofloxacin
- delafloxacin
linezolid considerations
- toxicity if use more than 2 weeks (bone marrow suppression)
- SSRI interaction
CDC 7 core elements of hospital antimicrobial stewardship programs (ASP) essentials
1) hospital leadership commitment
2) accountability
3) pharmacy expertise
4) action
5) tracking
6) reporting
7) education
linezolid DDI
SSRIs
daptomycin DDI
statins
pharmacy based stewardship interventions
a) document indication
b) IV to PO switch
c) dose adjust/optimization
d) time sensitive automatic stop orders
e) penicillin allergy assessment
f) detection/prevention of antibiotic DDIs
g) formulary restriction and preauthorization
duration of antibiotics for a complicated intra-abdominal infection with adequate source control?
4 days
STOP-IT trial!
what type of allergy can Bactrim cause
type IV –> delayed, cell-mediated (T cells) not antibody mediated!!
type I allergies
IgE mediated –> release histamine and other mediators from mast cells and basophils
severe penicillin allergy definition and options
definition
- anaphylaxis, hives, SOB, serious skin reaction (SJS, TENS, DRESS)
options
- alternate agent
OR
- desensitize IF no other non beta-lactam option
non-severe penicillin allergy definition and options
definition
- skin rash
options
- challenge a cephalosporin or carbapenem
penicillin cross reactivity with cephalosporins
very low
1st gen is more reactive than 3rd and 4th gen
check R1 side chain
penicillin cross reactivity with carbapenems
very low
check R1 side chain
penicillin cross reactivity with aztreonam
NONE –> CAN USE IF SEVERE PENICILLIN ALLERGY!
BUT caution if ceftazidime or cefiderocol allergy
cephalosporin cross reactivity with aztreonam
SAME SIDE CHAIN: ceftazidime, cefiderocol
therefore do not use if allergy to these ones!
penicillin allergy alternatives
- vancomycin
- fluoroquinolones
- clindamycin
- aztreonam
BUT inc cost, inc MDR, inc AE risk, inc c diff risk
how to assess penicillin allergy?
what happened? –> severity
when? –> dec overtime
anything similar?
check inpatient and outpatient for similar
**if have taken similar and tolerated after the documented allergy –> probably less severe, can use again!
penicillin skin testing
1) puncture testing (superficial)
histamine (+ control), saline (- control), penicillin
think PPD
2) intradermal testing (deeper)
3) low dose PO penicillin or amoxicillin
when do you use penicillin skin testing
type 1 hypersensitivities (IgE mediated)
desensitization process
- TEMPORARILY allows drug toleration
- ONLY if alternatives cannot be used
- start low dose, double every 15 min if tolerating
- IV preferred, could do SQ or PO
which drugs get formulary restricted?
- broad spectrum
- last resort
- if have shortage
- expensive
biggest rule of stewardship
use the most narrow spectrum that will treat the infection
empiric treatment steps
1) identify the most likely pathogen based on location and type of infection
2) select antibiotic based on the pattern of susceptibility for that most likely pathogen
- antibiogram!
STILL ORDER THE CULTURE!
what is an antibiogram
susceptibility rates of bacteria OVER A DEFINED PERIOD OF TIME
- % of organism isolates that were susceptible
definitive treatment steps
the culture gives exact organism AND ITS EXACT SUSCEPTIBILITY
therefore, use that and consider PK parameters and if can get to site of infection
NO ANTIBIOGRAM!!
MSSA drugs of choice
nafcillin (IV)
oxacillin
dicloxacillin
cefazolin (IV)
cephalexin
MRSA drugs of choice
ceftaroline
vancomycin
daptomycin
linezolid
in addition (if community acquired):
bactrim
clindamycin
doxycycline
pneumonia 3 most common organisms
SMH
strep pneumo
morax catt
h influenzae
streptococci drugs of choice
penicillins
cephalosporins
vancomycin
only if strep pneumoniae:
levofloxacin
moxifloxacin
NOT CIPRO –> DOESN’T COVER!
what do cephalosporins not cover?
LAME
listeria
acinetobacter
MRSA (except ceftaroline)
enterococcus
enterococci drugs of choice
ampicillin
vancomycin
daptomycin
linezolid
NOT CEPHALOSPORINS
what does ertapenem not cover?
ertAPEnem
acinetobacter
pseudomonas
enterococcus
pseudomonas drugs of choice
piperacillin/tazobactam
cefepime
ceftazidime
cefiderocol
carbapenems (not ert)
aztreonam
aminoglycosides
fluoroquinolones (not moxi) –> only po option!
acinetobacter drugs of choice
VERY RESISTANT –> need susceptibilities!!
ampicillin/sulbactam (the sulbactam is active)
cefiderocol
meropenem
penicillinases drugs of choice
*add a beta-lactamase inhibitor
amox/clavulanate
ampi/sulbactam
piper/tazobactam
cephalosporinases drugs of choice
carbapenems
ESBL drugs of choice
carbapenems
piperacillin/tazobactam
CRE (carbapenem resistant enterobacteriacae) drugs of choice
cefiderocol
if KPC (klebsiella):
ceftazidime /avibactam
meropenem/vaborbactam
imipenem/cilastatin/relebactam
oral anaerobes drugs of choice
above diaphragm
peptostreptococcus, prevotella
CLINDAMYCIN
amox/clav, ampi/sulb, pip/tazo
carbapenems
intestinal anaerobes drugs of choice
below diaphragm
Bacteriodes –> B. fragilis
METRONIDAZOLE
amox/clav, ampi/sulb, pip/tazo
carbapenems
c diff drugs of choice
1st: fidaxomicin PO
2nd:
vancomycin PO
metronidazole IV (if fulminant)
HECK Yes organisms
Hafnia alvei
Enterobacter cloacae
Citrobacter freundii
Klebsiella aerogenes
Yersinia enterocolitica
HECK Yes organisms drugs of choice
cefepime
piperacillin/tazobactam ??
carbapenems
AVOID 3rd gen cephalosporins –> ceftriaxone
what do you avoid in HECK Yes organisms? why?
ceftriaxone (3rd gen cephal)
inducible AmpC
- appear S on report, after exposure will inc AmpC beta lactamases and get resistant
which HECK Yes organisms are highest risk for inducible AmpC
ECK
enterobacter cloacae
citrobacter freundii
klebsiella aerogenes
what is the only case you can use ceftriaxone in AmpC organsism?
to treat uncomplicated cystitis
syphilis risk factors/more common in
men
black
20-29 yrs
what is unique about syphilis?
STAGES!! (3)
cause and transmission of syphilis
cause: spirochete –> treponema pallidum
transmission: direct mucocutaneous contact aka sexual transmission
syphilis stage 1
primary
- chancre at infection site –> genitals (penis, vagina, rectum, anus) OR lips/mouth
- symptomatic OR asymptomatic
**epidermal/local signs and symptoms
syphilis stage 2
secondary
- only 25% develop second stage (NOT ALL)
- develops within 6 months
- rash, lymphadenopathy, fatigue, organ involvement, fever, rash
- 75% risk of hematogenous dissemination (bacteremia)
**systemic signs and symptoms
syphilis stage 3
latency
early latency
- within 1-2 years
- asymptomatic
late latency
- complicated organ involvement
- CV, gummoatous lesions
- **neurosyphilis of brain and spinal cord (neurologic complications)
syphilis asymptomatic screening/Dx
screen if risk factors
- acquisition: black, male, 20-29
- transmission: pregnant
syphilis symptomatic screening/Dx
if risk factors (transmission, acquisition)
then presumptive Dx
- 2 tests
- treponemal: if every infected
- nontreponemal: if active infection
primary, secondary, early latency syphilis treatment
benzathine penicillin G
IM into butt
2.4 million U
x1
late latency syphilis treatment
benzathine penicillin G
IM into butt
2.4 million U
qweek for 3 weeks total!!!
neurosyphilis and ocularsyphilis treatment
1st: aqueous crystalline penicillin G
IV
18-24 million U /day –> continuous IV or 3-4 mill U q4h
10-14 days!
2nd: aqueous crystalline penicillin G
IM into butt
2.4 million U
QD
+
probenecid
PO
500 mg QID
both for 10-14 days!
what does chlamydia commonly impact/cause in men and women?
women
- impacts cervix
- cervicitis
- could be PID, urethritis –> serious
men
- nongonococcal urethritis
chlamydia risk factors/most common in
women
15-24
black
treatment for chlamydia
1st: doxycycline 100mg po BID x 7 days
2nd: azithromycin 1g po x1
treatment for chlamydia in pregnancy
1st: azithromycin 1g po x1
gonorrhea symptom onset
appear LATER –> within 10 days
gonorrhea presentation
urethritis
cervicitis
PHARYNGITIS
pid
what can untreated gonorrhea lead to?
bacteremia (hematogenous dissemination)
arthritis
meningitis
gonorrhea risk factors/more common in
men
black
unique about gonorrhea
pharyngitis
later onset of symptoms (w/i 10 days)
high resistance to antibiotics
first line gonorrhea treatment
1st: ceftriaxone 250mg IM x 1
first line gonorrhea treatment if PCN allergy
azithromycin 2g PO x1
+
gentamicin 240mg IM x 1
first line gonorrhea treatment in pregnancy
ceftriaxone 250mg IM x1
+
azithromycin
first line gonorrhea treatment in disseminated infection
ceftriaxone qd for >7 days
THEN
cefixime + azithromycin
is PID medically urgent?
YES
inpatient PID treatment
cefotetan/cefoxitin IV
+
doxycycline PO
+ metronidazole IF abcesses
14 days
outpatient PID treatment
ceftriaxone/cefoxitin (+ probenecid) IM x1
+
doxycycline PO
+ metronidazole IF abcesses
14 days
can you change the dosage form of PID treatment
yes, can change to PO throughout treatment
what is EPT used for
chlamydia ONLY
(and gonorrhea ig lol)
EPT chlamydia treatment
azithromycin 1g PO x1
EPT gonorrhea
cefixime 400mg PO x1
+
azithromycin 1g PO x1
when do you screen for chlamydia or gonorrhea
if sexually active and have s/s
what Dx/screening test is used for gonorrhea and chlamydia
NAATs (nucleic acid amplification tests)
ALWAYS test for both if testing for one!! –> similar s/s, common coinfection!
importance of communicable disease
**MOST IMPORTANT CONTRIBUTOR TO MORTALITY AND MORBIDITY HISTORICALLY
- decline in North
- are infectious diseases –> most are treatable and cureable
- POVERTY plays huge role
major international health organizations
- WHO
- world bank - intergovernmental agency
- multilateral agencies: UN, UNICEF
measures of global health
1) morbidity
- disease state, disability, poor health due to any cause
- incidence, prevalence, incidence of developing new medical condition
2) mortality
- number of deaths adjusted to population per time
3) disability adjusted life years (DALY)
- measures time lived with disability and time lost due to premature mortality
4) quality adjusted life years (QALY)
- expected survival + expected QOL
- measures the value placed on expected years of survival
other social determinants of health that impact global health
- vulnerable settings
- primary healthcare
- non-communicable diseases
- mental health
- air pollution and climate change
- maternal and child health
- nutrition
- injuries
- sexual and gender violence
poverty and infectious disease
poverty is a cycle!!
poverty –> low income –> poor sanitation and healthcare –> INFECTIOUS DISEASE –> dec work/productivity –> low income –> ….
other impacts on poverty and infectious disease
- variations in political/gov infrastructure
- variations in economic, social, cultural factors
- who controls government and makes health policy
- war, conflict, natural disasters
- climate differences –> insect vectors, intermediate hosts, weather patterns
infectious disease considerations
- resistance
- vaccine hesitancy
- diarrheal and respiratory illness
- global influenza pandemic
- “big four”: HIV, malaria, hep C< TB
- neglected tropical infections
- high threat pathogens
top 10 infectious diseases
0.5) COVID
1) HIV/AIDS
2) ebola
3) SARS
4) malaria
5) anthrax
6) cholera
7) bubonic plague
8) influenza
9) typhoid fever
10) small pox
malaria organism
plasmodium parasites
most common: P falciparum
malaria transmission
mosquitos
malaria disease impacts
infects RBCs
malaria s/s
mild: flu like
severe: organ failure –> hemoglobinuria (hemorrhaging)
how fast do you want to treat malaria?
within 24-48 hours, can progress quickly
uncomplicated P. falciparum malaria first line
artemether + lumefantrine
- IM or PO
- fewer AE
second line uncomplicated malaria
artesunate + amodiaquine
- IV or PO
- caution: hepatic and renal impairments
- more AE: GI, QT, …
duration and dosage form
mild –> po
severe –> iv
3 days
when do covid symptoms appear
5-6 days after infection
which is the most common covid presentation
mild-moderate
why did covid spread rapidly?
superspreaders
asymptomatic spread
mild spread
disease course of covid
stage 1: early infection
- all viral response phase
- mild s/s
- mild clinical s/s
stage 2: respiratory phase
- viral response dec
- host inflammatory response inc
- SOB, hypoxia
- abnormal chest imaging
stage 3: hyperinflammation phase
- all host inflammatory reponse
- SIRS, shocks, ARDS, sepsis
- inc inflammation markers –> IL-6, BNP, CRP, D-dimer
what is ARDS
acute respiratory distress syndrome
- stage 3 of covid (hyperinflammatory)
- so much fluid in lungs that there is little gas exchange
- need to be in ICU
covid complications/risk factors
*these cause mortality, not really the virus itself
- CV –.> inc MI
- DM –> inc DKA, inc ARDS
- hepatobiliary
- GI
- renal – inc AKI
- neurologic
- thyrotoxicosis
- muscultocutaneous –> rash
- hematologic –> lymphopenia, thrombocytopenia (low platelets)
covid variants
1) original
2) delta variant
- inc tranmissability
- dec vaccine efficacy
- inc disease severity
3) omicron
- inc inc transmissability
- dec dec vaccine efficacy
- many subvariants
*major today are subvariants of omicron
**need to consider the predominant variant at the time of publications!!!
neutralizing monoclonal antibodies
- pre-exposure and symptomatic
- not FDA approved
- bind to binding site therefore prevent entry into host cells
- NOT ACTIVE AGAINST OMICRON – DO NOT USE
paxlovid generic, dose, duration
nirmatrelvir/ritonavir
300mg/100mg –renal impaired–> 150mg/100mg
5 days ONLY NO MORE
nirmatrelvir/ritonavir indication
outpatient, high risk (atleast 1 risk factor), 12+, positive test, within 5 days of symptoms onset
paxlovid ddi
CYP 3A4 inducer –> many
bc ritonavir
molnupiravir dose, duration
800mg po q12h
- no renal/hepatic dose adjust
5 days ONLY
molnupiravir ddis
few
high barrier to resistance
molnupiravir CI
PREGNANCY AND BREASTFEEDING
molnupiravir indication
outpatient
mild-mod illness
high risk (1 or more risk factors)
18+
not pregnant/breastfeeding
within 5 days of symptoms
positive test
order of therapies for outpatient, mild-mod illness, high risk, not on supplemental o2
1st: nirmatrelvir/ritonavir
2nd: remdesivir
3rd: molnupiravir –> only if no other options
therapies for outpatient, mild-mod illness, no supplemental o2, not high risk
symptoms management ONLY
remdesivir dosage form, dose, duration
IV ONLY
200mg IV LD –> 100mg IV qd
- caution GFR < 30!!
5 days
remdesivir AEs
well tolerated overall
- inc LFT
- phlebitis
- extremity pain
remdesivir indication
don’t need all:
outpatient OR inpatient, mild-mod disease, no oxygen, high risk, little oxygen
- only use in severe if no other option (severe = O2sat < 94%)
1) hospitalized, no o2, high risk
2) hospitalized, some o2
remdesivir CI
GFR < 30 maybe
on ventilation
on ECMO
is remdesivir FDA approved?
YES
remdesivir benefit
dec time to clinical recovery
NO mortality benefit
broad antiviral activity
corticosteroid drug, dose, duration, route
dexamethasone
6 mg qd
IV or PO
10 days or until discharge
dexamethasone indication
hospitalized (all!)
IL-6 antagonists
sarilumab –> not fda approved
tocilizumab –> FDA APPROVED
tocilizumab dose, route, duration
IV
8mg/kg (max 800mg)
x1 (over 1hr)
tocilizumab AE
inc LFT
neutropenia, thrombocytopenia
general infection
SERIOUS INFECTIONS
- TB, bacterial, fungal, bowel preforation
**NEED TO SCREEN TB AND INFECTION RISK BASELINE!
tocilizumab indication
1) hospitalized, need o2/vent/ecmo, getting dexamethasone
2) hospitalized, severe/progressive, inc inflammatory markers (CRP > 75)
1) hospitalized, o2, rapidly inc o2 demand, systemic inflammation
2) hospitalized, need HFNC o2 or NIV
3) hospitalized, need vent or ecmo
tocilizumab regimen
ALWAYS WITH SYSTEMIC GLUCOCORTICOIDS (they are the standard)
baricitinib dose, duration, route
PO
4mg qd
14 days or until discharge
baricitinib AE
infection
thrombosis
CAUTION: current infection, with IL-6 tocilizumab bc of immunosuppression risk
baricitinib indication
1) hospitalized, severe, need o2/vent
2) hospitalized, need o2/vent/ecmo/niv
3) hospitalized, need o2, rapidly inc o2 need, systemic inflammation
4) hospitalized, need nfnc or niv
5) hospitalized, need vent/ecmo
baricitinib regimen
with dexamethasone
FDA approved
first line hospitalized, need o2/vent/ecmo/niv
dexamethasone + IV tocilizumab / PO baricitinib
is it SOC to give antibiotics for covid
NO
- bacterial coinfection with COVID is uncommon
is it SOC to give therapeutic anticoagulation in covid
covid: inc time to clot, but have some disseminated clots –> concern over bleed risk
if hospitalized, on supplemental o2, d-dimer > 4xULN (aka > 2000), no ICU: THERAPEUTIC heparin
all else (less severe and more severe): PROPHYLATIC heparin
definition of high risk
**pretty much everyone, especially in hospital
- cancer
- CKD
- chronic lung
- chronic liver
- CF
- DM
- diability
- heart issue –> HF, CAD
- HIV
- mental health
- dementia
- obese
- immunodeficiency
- pregnant
- smoking
- SOT
- TB
what is not included in the risk factors for high risk
- asthma
- HTN
which COVID-19 therapies are FDA approved
- remdesivir
- tocilizumab
- baricitinib
