Exam 2 Falcione stuff Flashcards
types of antibiotic resistance mechanisms for gram negative organisms
- loss of porin channels
- increased efflux pumps
- enzymatic degradation (Beta lactamases, AMEs)
- changes in the binding site
define intrinsic resistance
bacteria naturally harbor & express the genes in their chromosomes (chromosomal or inherent resistance)
define acquired resistance
the bacteria do not naturally harbor in their chromosomes, genes are acquired, typically from other bacteria they encounter
define inducible
genes that are typically not being expressed
define constitutive
gene that is always on/expressed
E. coli beta lactamases
-can produce ESBLs
-some harbor plasmids for the beta lactamase TEM-1
what does TEM-1 do
inactivates aminopenicillins but not 1st generation cephalosporins
klebsiella beta lactamases
ESBLs, AmpC, KPC/CRE
via MDR plasmids
proteus beta lactamases
ESBLs, some harbor plasmids that encode TEM-1
enterobacter, citrobacter, and serratia beta lactamases
intrinsic resistance to aminopenicillins, 1st and 2nd Gen Cephs due to AmpC
inducible resistance with 3rd gen Cephs due to mutants constitutively producing high levels of beta lactamase
how many ambler classes are there
4
what bacterial pathogens are classified as enterobacterales
escherichia, klebsiella, proteus, enterobacter, citrobacter, serratia
enterobacterales grow in what environment
they are facultative anaerobes so they can grow/proliferate in aerobic or anaerobic conditions
pseudomonas microbio characteristics
gram negative rod arranged in pairs
obligate aerobe
non lactose fermenter
oxidase positive
pseudomonas resistance
inherent to many antibiotics
mutation in PBP
BL production
decreased outer membrane porin expression
ESBLs
efflux pump upregulation
anti infectives with spectrum of activity that includes pseudomonas aeruginosa
aminoglycosides
aztreonam
cefepime
cefiderocol
ceftazidime
ceftazidime/avibactam
ceftolozane/tazobactam
ciprofloxacin, levofloxacin
delafloxacin
imipenem/cilastatin
imipenem/cilastatin/relebactam
meropenem and meropenem/vaborbactam
piperacillin/tazobactam
polymixin E and polymixin B
acinetobacter drug of choice
ampicillin/sulbactam
anti infectives with spectrum of activity that includes anaerobes
cephamycins and carbapenems
CDC definition of CRE
CRE: members of the enterobacterales order resistant to at least one carbapenem antibiotic or producing a carbapenemase enzyme
*for bacteria that are intrinsically not susceptible to imipenem, resistance to at least one carbapenem other than imipenem is required
______ interact with _____
carbapenems interact with valproic acid
which BLIs include a beta lactam structure
tazobactam, sulbactam, clavulanate
which BLIs are non beta lactam BLIs
avibactam, vaborbactam, relebactam
which anti infectives are distinguished for poor or absent spectrum of activity for gram positive pathogens
ceftazidime and aztreonam
which anti infective does not require dose adjustment for renal insufficiency
ceftriaxone
beta lactam general mechanism
inhibit cell wall synthesis
aminoglycoside general mechanism
inhibit protein synthesis
aminoglycoside chemical component
amino sugars with glycosidic links to aminocyclitol
how do aminoglycosides inhibit protein synthesis
bind to 30S subunit
aminoglycosides spectrum
greatest utility: therapy of serious systemic infections due to GNRs that can grow aerobically: ex pseudomonas, enterobacterales
less susceptible to aerobic gram + cocci and aerobic gram - cocci
generally resistant to anaerobes, stenotrophomonas, burkholderia
aminoglycosides elimination
almost entirely as unchanged drug via glomerular filtration: elimination rate increases in proportion with creatinine clearance
**regimen must be adjusted with impaired renal function to avoid nephrotoxicity
**TDM required
aminoglycosides pharmacodynamics
concentration-dependent killing
post antibiotic effect occurs– permits less frequent administration while still maintaining antibacterial activity
what is the most common resistance mechanism of aminoglycosides
aminoglycoside modifying enzymes (AMEs)
chemical incompatibility with aminoglycosides
admixture with penicillins: can cause precipitation and inactivation of both drugs– avoid mixing in same solution or administering via same IV line
aminoglycoside drug interactions
vancomycin
loop diuretics
polypeptide antibiotics
aminoglycoside toxicities
nephrotoxicity, ototoxicity, neuromuscular toxicity
aminoglycoside dosing strategies
high dose, extended interval dosing: effective and may reduce ototoxicity/nephrotoxicity
complications of HAP/VAP
pleural effusion, empyema, lung abscess, respiratory failure, septic shock
what is the site of infection for pneumonia
alveoli
pathophysiology of HAP
- bacterial contamination of respiratory secretions from nonsterile oropharynx and nasopharynx
- pooling of respiratory secretions normally expelled by changing positions or posture and by coughing
- inactivity allows secretions to pool by gravity, interfering with the normal diffusion of oxygen and carbon dioxide in the alveoli
definition of HAP
pneumonia occurring 48 hours or more after hospital admission – not incubating at time of admission
definition of VAP
associated with mechanical ventilation pneumonia begins 48 hours after endotracheal intubation
when to use 2 antipseudomonal drugs for HAP/VAP
- risk factors for MDR pseudomonas & GNR: prior IV antibiotics within 90 days, structural lung disease (bronchiectasis, cystic fibrosis)
- high quality gram stain from respiratory secretion with numerous & predominant GNRs
- patients in ICU with >10% pseudomonas isolates resistant to monotherapy regimen, local ICU antibiogram data unknown
- high risk for mortality: ventilator support required for HAP, septic shock
when to use MRSA coverage with vancomycin or linezolid for HAP/VAP
- risks for MRSA: prior IV antibiotics within the past 90 days, hospital unit with >10-20% MRSA, unknown MRSA prevalence in the hospital unit, prior MRSA in a culture or non-culture diagnostic
- high risk of mortality: need for ventilator support due to HAP, septic shock
which aminoglycosides can be used for pseudomonas
tobramycin, amikacin, gentamicin
HAP/VAP duration of therapy
7 total days empiric + directed
which anti infectives are not appropriate for monotherapy for HAP
aminoglycosides due to unreliable distribution
some inciting events for peritonitis
- diverticulitis
- appendicitis
- infections of the liver and biliary system: cholangitis, cholecystitis, liver abscess
most common organisms implicated in intra abdominal infections
- gram positive aerobic cocci: strep, enterococcus, staph
- anaerobes: bacteroides, clostridium, prevotella, peptostreptococcus, fusobacterium, eubacterium
- facultative and aerobic gram negative: e coli, klebsiella, pseudomonas, proteus, enterobacter
duration of therapy for bacteremia for patients who are afebrile, hemodynamically stable, and appropriate source control
1 week, & repeat blood cultures unnecessary , & can be treated with oral antibiotics
cystitis treatment options
nitrofurantoin, TMP/SMZ, fosfomycin
pyelonephritis treatment options
ciprofloxacin, ceftriaxone, piperacillin/tazobactam, ampicillin
cefepime is stable/not stable for what
stable for AmpC producing enterobacterales
aminopenicilln/BLI is stable/not stable for what
activity against Class A BLs and some ESBLs
not KPCs
Pip/tazo is stable/not stable for what
activity against Class A BLs and some ESBLs
not KPCs
ceftazidime is stable/not stable for what
vulnerable for AmpC producing enterobacterales
ceftolozane/tazobactam is stable/not stable for what
activity for cefepime-resistant pseudomonas aeruginosa
ceftazidime/avibactam stable/not stable for what
Class A (ESBLs and KPC)
Class C (AmpC)
some class D
not MBLs
cefiderocol is stable/not stable for what
stable for ESBL, AmpC, CRE
carbapenems are stable/not stable for what
ESBL and AmpC-producing enterobacterales
not MBLs
aztreonam is stable/not stable for what
is not inactivated by MBLs but can be hydrolyzed by co-produced enzymes such as ESBLs, KPCs: use in combo with ceftazidime/avibactam to protect against other enzymes to allow activity against MBLs
