Introduction to antimicrobial drugs and cell wall synthesis inhibitors (INCOMPLETE) Flashcards
What factors play in to determining appropriate antibiotic therapy
most likely organism causing infection
likely susceptibility of the organism to antibiotic
site of infection
patient factors - i.e comorbiditites
also cost
What “host factors” must be taken into account prior to prescribing an antibiotics
Immunosuppression, kidney or liver disease
What is Empiric therapy
broad-spectrum treatment prior to identification of organism
What is the prescription of a broad-spectrum antibiotic prior to the organism identification called
Empiric therapy
Critically ill patients require what type of therapy for what is presumed an bacterial infection
empirical therapy
when is emperic therapy indicated
critically ill patients
If a critically ill patient present with a history of a prior MRSA infection, with a new skin infection - what type of therapy is necessary for this patient
a empiric MRSA coverage antibiotic
what does the choice of broad-spectrum antibiotics for empirical treatment depend on
the patient clinical condition, potential site of infection and knowledge of microbes that may be causing infection
What are antibiotic susceptibility considerations based on
patterns of antibiotic sensitivity (based on local antibiogram and historical data)
lab testing - MIC and MBC
What is MIC and what does it stand for
Minimal inhibitory concentration - lowest concentration of drug that inhibits bacterial growth
what is MBC and what does it stand for
Minimal bactericidal concentrations - the lowest concentration of drug that kills bacteria
What is the MOA for bactericidal medications
antibiotic kills the bacteria
host defenses NOT required
if an antibiotic kills the bacteria - what type of antibiotic is it
bactericidal antibiotic
What type of antibiotic inhibits the bacterias replication and requires host defense
bacteriostatic antibiotic
What is the MOA for bactericidal medications
antibiotic kills the bacteria
host defenses NOT required
what is MOA for bacteriostatic medications
antibiotic inhibits bacterial replication; does not kill bacteria
host defense REQUIRED
what are the two antibiotic mechanism of actions
Bactericidal and bacteriostatic
other considerations for choosing antibiotic therapy
route of administration (oral, IV, IM)
tissue distribution (CNS penetration)
side effects and toxicities (allergies, kidney toxicity in context of other nephrotoxic drugs or renal insufficiencies)
routes of metabolism/elimination
in choosing antibiotic therapy what considerations do we have to make for immune status
neutropenia, cell-mediated defects, etc.
bactericidal drugs for compromised hosts
in choosing antibiotic therapy what anatomical considerations do we have to make
abscesses, necrotic tissues, foreign material
match drug bioavailability to site of infection
bactericidal drugs for “immune-protected” sites (CNS, eye, bacterial endocarditis)
What is it called when a percentage of the total drug administered reaches the systemic circulation
bioavailability
Define Bioavailability
percentage of drug that reaches the systemic circulation of the total amount administered
Renal function consideration in choosing antibiotic therapy
dose adjustment required for some drugs that are renally excreted
what drug-drug interactions with antibiotics need to be considered
antibiotic effects on INR for patients on warfarin
what age groups do we avoid using chloramphenicol and sulfonamides
neonates
what age groups do we avoid tetracyclines with
young children - discolors teeth
who should avoid amino-glycosides
pregnancy - ototoxic effects on fetus
What is it called when the combined effect of two antibiotics is greater than the sum of their independent activities?
Synergy
What is synergy
when the combined effect of two antibiotics is greater than the sum of their independent activities
what is it called when the combination of two antibiotics is less than the sum of their independent activities?
Antagonism
what is antagonism
when the combined effect of two antibiotics is less than the sum of their independent activities
What is it called when the effect of two antibiotics equals the sum of their independent activities?
Indifference
what is indifference
when the effect of two antibiotics equal the sum of their independent activities
When is it warranted to use antibiotic combinations
- prevention of bacterial resistance
- treatment of polymicrobial infections
- initial therapy for critically ill patients with unknown source of infection
what increases with combination therapy without good rationale
toxicity and cost with little to no benefit
why is tuberculosis treated with combination therapy
to decrease the resistance to monoantibiotics
What is chemoprophylaxis
the use of drugs to prevent disease
example: prophylactic antibiotic for post joint replacement dental appointment
what are examples of times antibiotic prophylaxis is necessary
prior to surgery
pts undergoing dental extractions who have prosthetic heart valves or joints
prevention of TB or meningitis in pts who are in close contact to infected individuals
PJP in HIV-infected pts
and chronic recurrent UTIs
What are cell wall synthesis inhibitors
penicillin - sensitive and resistant
cephalosporins
monobactam
carbapenems
glycopeptides
What are gram positive organisms (5)
Steph and strep
bacillus anthracis
enterococcus species
clostridium species
What are common gram negative organisms (8)
enterobacter colacae
helicobacter pylori
salmonella
hemophilus influenze
pseudomonas
klebsiella
legionella
escherichia coli
what is selective toxicity
the basis for effective antibacterial treatment
What is the basis for effective antibacterial treatment
selective toxicity
What drug is a lipopeptide antibiotic that targets resistant gram positive bacteria?
Daptomycin - it is newly developed
What is Daptoymycin
a newly developed lipopeptide antibiotic that targets resistant gram positive bacteria
What are the ribosomal subunits of bacteria and what do they make
50S and 30S and they combine to make 70S ribosomal mRNA complex that has significant differences from the 80S ribosomal RNA of mammalian cells
What is the term for antibiotics that target the ribosome
protein synthesis inhibitors
what are protein synthesis inhibitors
antibiotics that target the ribosome and are typically bacteriostatic
Types of Cell wall inhibitor antibiotics are
Penicillins, cephalosporins, aztreonam and carbapenems
if a autolytic enzyme is activated what is the response
it causes breaks in the bacterial cell wall
what is the MOA of beta-lactam antibiotics
interfere with cell wall synthesis by binding to PBP and compromise the cell wall integrity - osmotic lysis
enhances cell wall breakdown my activating autolytic enzymes (autolysins)
what does PBP stand for
penicillin binding proteins
What do penicillins consist of
thiazolidine ring
beta-lactam ring
side chain (R)
what is the beta-lactam ring needed for
essential for antibacterial activity
what determines the antibacterial spectrum and pharmacologic properties of a particular penicillin?
The side change (R)
what organisms express beta-lactamase enzymes and are resistant to Penicillin G?
S. aureus and anaerobic bacterium Bacteroides fragilis
what is penicillin G susceptible to?
hydrolysis by Beta-lactamase enzymes
What do the Side Chain (R) determine
the antibacterial spectrum and pharmacologic properties of a particular penicillin
What are the different classifications of penicillins
Natrual penicillins (penicillinase-senstive)
aminopenicillins(penicillinase- senstivie)
semi-synthetic (penicillinase- resistant)
ureidopenicilin
beta-lactamase inhibitors
what are the natural penicillins types
penicillinase-senstive
penicillin G
penicillin V
what are the aminopenicillins types
penicillinase-senstive
ampicillin
amoxicillin
What are the semi-synthetic penicillin types
penicillinase-resistant
nafcillin
oxacillin
dicloxacillin
what is the ureidopenicillin types
piperacillin - antipseudomonal
what are the beta-lactamase inhibitors types
ampicillin/sulbactam(unasyn)
amoxicillin.clavulonate(augmentin)
pipieracillin/tazobactam (zosyn)
How is Penicillin V administered
Oral formulation
How is penicillin G administered
IV or IM formulation
what type of microbial does penicillin G, V attack
- gram positive cocci: STREP
- gram Negative cocci : Neisseria meningitidis
- Anaerobes (oral)
- spirochetes
- other organisms such as pasteurella multocidal (cat bites)
NO STAPH coverage
What are the gram positive cocci that penicillin G and V treat
STREP
S. pneumoniae
Group A Strep (s. pyogenes)
Group B strep (s. agalactiae)
Group C, G streptococcus
Viridans streptococci
What gram negative cocci does penicillin G and V treat
Neisseria meningitisis: meningitis and bacteremia
What anaeobes are penicillin G and V not useful for
bacteroides fragilis and other bacteroide species due to the presence of beta-lactamase
therefore, not useful for intra-abdominal infections
What cat bite related organism is affected by penicillin G and V?
Pasteurella multocida
What spirochetes do penicillin G and V treat
Treponema pallidum (syphilis) and Borrelia burgdorfi (lyme disease) - although rarely used
What anaerobes do penicillin G and V treat
they are good against oral anaerobees: Peptostreptococcus, prevatella, fusobacterium, clostridium species
what type of microbial does penicillin G and V not affect
Staph
What is the most common use for penicillin V
group A strep - S. PYOGENES
What patients require dose adjustments when using Penicillin G
patient with Renal insufficiency
How is penicillin G administered
usually 1-4million units IV Q4 hours due to short half-life (.5hrs) requires frequent dosing and has poor oral bioavailability and acid labile
What are the IM formulations of Penicillin G
Procaine penicillin and Benzathine penicillin
requires mixing with another med for better absorption IM
Side effects of Penicillin G
rash, anaphylaxis and seizures
when is penicillin contraindicated
with a history of hypersensitivity to beta-lactams antibiotics, and use in caution with patients with asthma or hx of multiple allergens
what is resistant to Penicillins
98% of S. Aureus contain a penicillinase which hydrolyzes the beta-lactam ring
what medication should be avoided if S.aureus is suspected
Penicillin G
What does methicillin work against
Gram positive cocci (STREP)
S. aureus, S. epidermidis (if susceptible)
NO GRAM NEGATIVE activity
what type of penicillin is methicllin
semi-synthetic penicillin - first penicillin developed to resist hydrolysis by staphylococcal beta - lactamase
What is methicillin to cause as an adverse side effect
interstitial nephritis
what is Nafcillin and oxacillin
IV/IM formation(acid labile) - more common than methicillin
what is dicloxacillin
PO formulation - more common than methicillin
what semi-syntheitc penicillins have no renal or hepatic impairment dose adjustments
dicloxacillin and oxacillin
What patients require caution when planning to use a nafcillin antibiotic
patients with renal and hepatic impairment
What semi-synthetic penicillin do you need to use caution for renal and hepatic impairment
nafcillin
What are oxacillin and nafcillin side effects
rash
GI upset
Elevated AST/ALT
neutropenia
allergic interstitial nephritis
What do aminopenicillins act against?
Gram positive Strep (penicllin-susceptible S. Aureus) (they are less active against Group B strep, S. penumonia and group B strep)
Gram negative (H. influenzea and E. coli)
what is ampicillin/amoxicillin highly active for
enterococci and listeria monocytogenese
What are the common side effects of ampicillin/amoxicillin
Rash
Diarrhea
what are the contraindications for the use of ampicillin/amoxicillin
hypersensitivity reactions to beta-lactam antibiotics
What is Beta-lactamase
it is produced by the bacteria and results in a resistance to beta-lactam antibiotics
what are examples of beta-lactamase inhibitor antibiotics
Ampicillin-sulbactam (Unasyn)(IV) and Amoxicillin-Clavulante (Augmentin) (PO)
What is the benefit of using a beta-lactamase inhibitor
it increases the spectrum of activity
what do beta-lactamase inhibitors act on
Gram positive (S. aureus susceptible ot MSSA)
Gram negative (H. influenza, E. coli, K.pneumoniae, K. oxytoca)
Anaerobes (bacteroides fragilis)
What type of penicillin is Piperacillin-Tazobactam (Zosyn)
Ureidopenicillin
what is piperacillin-tazobactam (zosyn) active toward
gram positive (No MRSA coverage)- strep
and has expanded gram negative coverage of P. aeruginosa, S. marcescens, E.coli and klebsiella)
Also excellent anaerobic activity for B. fragilis
what patients need to have the dose of piperacillin-tazobactam adjusted?
patients with renal insufficiency
What penicillins is considered the prototype
penicillin G (IV and IM)
What penicillin is considered acid-resistance
Penicillin VK (PO)
What penicillins are considered Beta-lactamase-resistant
methicillin
nafcillin
oxacillin
dicloxacillin (PO)
(Staph PCNs)
What penicillins are available for combo treatment
amoxicillin and ampicillin
What penicillin is considered “anti-pseudomonas”
piperacillin
what penicillins are combination treatments with beta lactamase inhibitors
augmentin (PO)
Unasyn (IV)
Zosyn (IV)
What are the three beta-lactamase inhibitor combination therapies
Amoxicillin/clavulanate (PO)
ampicillin/sulbactam(IV)
Piperacillin/Tazobactam(IV)
How are cephalosporins like penicillins
they contain beta-lactam ring and inhibit cell wall synthesis and are bacteriecidal
how are cephalosporins UNlike penicillins?
they are resistant to hydrolysis by many beta-lactamases
‘R1’ and ‘R2’ side chain substitutions alter the antibacterial spectrum and pharmacokinetics
What are cephalosporins
beta-lactam antibiotics derived from 7-aminocephalosporanic acid
What cephalosporins are LAME
organisms not covered by cephalosporins
Listeria
Atypicals (chlamydia, Mycoplasma)
MRSA and
Enterococci
(*except ceftaroline covers MRSA)
What are the first generation cephalosporins
cefazolin and cephalexin
what generation of cephalosporins are cefazolin and cephalexin
first generation
what are second generation cephalosporins
cefuroxime
what generation of cephalosporin is ceuroxime
second generation
what are third generation cephalosporins
ceftriaxone and ceftazidime
what generation cephalosporin are ceftraixone and ceftazidime
third generation
what are fourth generation cephalosporins
cefepime
what generation cephalosporin is cefepime
fourth generation
what are 5th generation cephalosporins
ceftaroline
what generation cephalosporin is ceftaroline
fifth generation
as the generations increase what happens to the gram negative and gram positive activity
as the generations increase, the gram negative activity increases and the gram positive activity decreases
What are the common adverse reactions to beta-lactam antibiotics
hypersensitivity
superinfections and
renal dose adjustments
What generations of cephalosporins do NOT enter the CSF
first and second generations
Cefazolin, cephalexin and cefuroxime (IV and PO)
What generations of cephalosporins penetrate the blood-brain barrier well, therefore being the drug of choice for treating CNS infections?
Third and fourth generation cephalosporins
ceftriaxone and ceftazidime
What are first generation cephalosporins used to treat?
Streptococci, S. aureus(MSSA), proteus mirabilis, senstive E. coli and Klebsiella species
(Skin and bone infection and surgical prophylaxis)
What are second generation cephalosporins used to treat?
they have improved gram negative coverage including beta-lactamase positive H. influenzae and Neisseria species and have slightly reduced gram positive activity
(inner ear infections/sinusitis)
What are third generation cephalosporins used to treat?
improved gram negative activity; they retain gram positive activity of the first generation drugs
(community-acquired pneumonia and CNS infections)
What are third generation cephalosporins used to treat?
gram negative rods including pseudomonas; loses gram positive activity
(nosocomial infections)
What are fourth generation cephalosporins used to treat?
excellent gram positive and gram negative activity including pseudomonas
Nosocomial infections
What are fourth generation cephalosporins used to treat?
efficacy against MRSA
No pseudomonas coverage
What generation of cephalosporins is indicated for skin, surgical prophyaxis (strep, MSSA, PEcK)
first generation
cephalexin and cefazolin
what generation of cephalosporins are indicated for ear infections, sinusitis and some GYN infections (PID)?
second generation
cefuroxime
What generation of cephalosporins are indicated for CNS penetration
third generation:
DOC is ceftriaxone(IV) but ceftazidime(IV) is also good
What generation of cephalosporins are indicated for gram positive and gram negative as well as pseudomonas
fourth generation
Cefepime (IV)
what generation of cephalosporins are indicated for the treatment of MRSA?
5th generation
Ceftaroline (IV)
What do monobactams inhibit
cell wall synthesis
What is the primary monobactam drug?
Aztreonam which is administered IV or IM
What is the benefit to Aztreonam?
there is no cross-allergenicity with the betra-lactams and those who are allergic to penicillins or cephalosporins may use these without concern
what is aztreonam used to treat?
broad gram negative activity including pseudomonas aeruginosa
They have no Gram positive or anaerobic activity
What are the adverse effects of Aztreonam?
generally well tolerated but occasionally cause GI upset
What type of drug class is vancomycin a part of
it is a glycopeptide and inhibits cell wall synthesis by binding to the D-Ala-D-Ala terminal and prevents cross-linking
Bactericidal
what is vancomycin used to treat?
drug-resistant gram positive infections including MRSA and C. diff
No gram negative activity
What are possible side effects of Vancomycin
“red man syndrome” - infusion related flushing
dose-dependent ototoxicity and nephrotoxicity
what is the DOC for MRSA
Vancymyocin because it is narrow spectrum
what is the cell membrane inhibitor?
daptomycin (IV Only)
what does daptomycin inhibit
it is a lipopeptide that inhibits the cell membrane
what is the administration of Daptomycin?
IV only
is daptomycin bactericidal or bacterostatic
bactericidal
What patients require dose adjustments for the use of Daptomycin
renal impairment
what spectrum drug is daptomycin
narrow spectrum for gram positive bacteria only such as MRSA and VRE
when is daptomycin used?
last line treatment to avoid overuse
What does carbapenems inhibit?
cell wall synthesis
what spectrum drug is carbapenems
one of the most broad spectrum antibiotics
what does carbapenems treat
gram positive cocci, gram negative rods and resistant gram negative rods (pseudomonas aeruginosa and enterobacter species as well as anaerobes
when is carbapenems implemented
last resort medication
what is beta-lactamase
it is produced by the bacteria resulting in resistance to beta-lactam antibiotics
what is the purpose of beta-lactamase inhibitors
they inactivate the beta-lactamases but not all beta-lactamases are able to be inhibited
what are the two beta-lactamases that are not able to be inhibited
chromosomal (Amp C) beta-lactamases
extended spectrum beta-lactamases (ESBL)
What are SPACE organisms
chromosomally mediated beta-lactamases
they have low level of constitutive production of AmpC Beta-lactamase
What does SPACE stand for
S- serratia marcescens
P - proteus (indole+) species and Providencia species
A - Acinetobacter baumannii
C - citrobacter freundii
E - enterobacter species
Others: Hafnia alvei, Morganella morganii
What are ESBLs
Extended Spectrum beta-lactamases
what are needed when treating SPACE organisms
they have beta-lactamases and need coverage with beta-lactamase inhibitors
Where are ESBLs found
mainly in E.coli and Klebsiella species and Carbapenems are used to treat
What are the three main Carbapenems
Imipenem (IV)
Meropenem (IV)
Ertapenem (IV)
why is imipenem used with cilastatin??
imipenem is inactivated by renal DHP and cilastatin inhibits DHPs
what are the adverse effects of impenem?
encephalopathy and seizures
what spectrum of activity do carbapenems have
gram positive organisms (NOT MRSA)
gram negative organisms
What gram positive organisms are carbapenems used for
MSSA, MSSE, S. pneumoniae and it has marginal activity against E. faecalis
What gram negative organisms are carbapenems used for
they are very active against enterobacteriaceae and pseudomonas and ESBL (space organisms)
Not MRSA
What is Fosfomycin
bactericidal - cell wall synthesis inhibitor that inhibits the enzyme pyruvyl transferase
what is fosfomycin commonly used to treat
UTI particularly those caused by E.coli and Entercoccus faecalis
also trains activity against some MDR organisms including ESBL-producing E.coli
what are side effects of fosfomycin
diarrhea and vaginitis
