Pharm antibiotics Part 1 Flashcards
Antibiotics that taget the cell wall and membrane?
- Beta Lactams
* Pen, Ceph, Carb, Mono - Glycopeptides
* Vancomycin - Cyclic lipopeptide
* Daptomycin
types of beta lactams
- Penicillins
- Cephalosporins
- Carbapenems
- Monobactams
Fxn of beta lactam ab
ALL HAVE BETA LACTAM RING
Fxn: inhibit bacterial cell wall synth
Penicillin fxn
inhibit cell wall synthesis
structural analogs of PBP binding site- PBP enzyme that facilitates cross linking and stability
Penicillin subgroups
- Natural penicillins (Narrow spectrum)
- Aminopenicillins (broad)
- Penicillinase resistant penicillins
- Anti-pseudomonal penicillins (broad)
- Penicillin/Beta lactamase inhibitors
Categorizes of penicillins
- Narrow spectrum penicillins
Natural penicillins= PENICILLIN V AND PENICILLIN G - Broad spectrum penicillins
Amino penicillins-> AMOXICILLIN AND AMPICILLIN
Amino w/beta lactamase inhib-> AMOXICILLIN/CLAVULANATE, AMPICILLIN/SULBACTAM
Antipseudomonal penicillin-> PIPERCILLIN/TAZOBACTAM
Natural Penicillins
ALL NARROW SPEC
1.PENICILLIN V-> greatest non bLactamase producing Gram positive ONLY SOME GRAM - FOR NEISSERIA
low systemic levels
2. PENICILLIN G->greatest non bLactamase producing Gram positive ONLY SOME
* Procaine penicillin G-> rapid acting
* Benzathine Penicillin G->long acting RHEUMATIC FEVER PROPHYLAXIS
* Combined repository (CR)-> combo of both
Rheumatic Fever prophylaxis + duration
Prophylaxis: Benzathine Penicillin G once a month-> for 5 years or till 21-> life long if valvular disease
Duration:
RF with Carditis + Residual heart disease= 10 yrs or 40 yo (which ever is longer)
RF with carditis NO residual= 10 yrs or 21 yo
RF w/out carditis= 5 yrs or until 21 yo
Treponema pallidum info and tx
TP= SYPHILIS (primary, secondary, tertiary)
Testing: Rapid plasma regain (RPR), Flouro trep ab absorp (FTA)
TX: NO KNOWN PCN RESISTANCE= Benzathine PCN for each
has neurosymptoms= Aquaeous Crystalline Penicillin G
Neisseria Meningitidis
Meningococcus
MOA: Gram Negative with endotoxin liberated from cell wall
TX:* High dose Penicillin G*
Empirically: if unsure use Ceftriaxone
Secondary contacts: rifampin or Ceftriaxone if prego
Vacc: Menactra and Bexero
Presentations: sudden fever, headache, stiff neck, N/V, sens to light
Children: inactivity, irritability, vomiting, poor reflexes
Penicillinase resistant penicillins
Anti-staphylococcal Penicillins
1.Oxacillin - for serious staph- endocarditis
2.Nafcillin- for serious staph- endocarditis
3.Dicloxacillin- skin and soft tissue infections- mild/mod
* Penicillinase producing staphylococci and streptococci
NOT MRSA
MRSA
NOT bETA LACTIMASE ISSUE
MUTATION W/ PENICILLIN BINDING PROTEIN
Tx: Vancomycin, Daptomycin
Methicillin Resistant Staphylococcus Aureus- specific to Staph
E
S
K
A
P
E
BUGS CAN BE HARD TO TREAT
E- Enteroccoccus faecium or E. coli idk
S- Staphylococcus aureus
K-Klebsiella pneumoniae
A- Acinetobacter baumannii
P-Pseudomonas aeruginosa
E-Enterobacter supp.
Impetigo
Cause: Staphylococcus Aureus or Streptococcus pyogenes
Tx depends on number of lesions: TRY TO COVER FOR BOTH BUGS
* Dicloxacillin
* Cephalexin
* narrow spec pen or ceph
Amino penicillins
- Amoxicillin- better oral than amp-> AOM, Lower resp tract inf-> PREFERRED FOR PNEUMOCOCCI
- Ampicillin-> h. pylori-> group B step sepsis in Neonates
Overall: effective againts GRAM + AND GRAM - BUT NOT PENICILLINASE RESISTANT
Aminopenicillin/Beta lactamase inhib
- Amoxicillin/Clavulanate-> COVER GRAM NEG -> ACUTE BACTERIAL SINUSITIS
- Ampicillin/Sulbactam-> PROPHYLAXIS FOR POST OPP INF IN APPENDICITIS
Streptococcus Pneumoniae
Pneumococcus
Gram + diplocci
diseases involved:
* Pneumonia-> Amox
* AOM-> Amox
* Acute bacterial sinusitis-> Augmentin
* Meningitis-> Penicillin G
Antipseudomonal Penicillin
4th gen-> Ureidopenicillin
Piperacillin/Tazobactam
* piper only combined with tazo
* GRAM + COVERAGE WITH PIPER
* GRAM NEG-> pseudomonas, E. Coli, Klebsiella
Indications: PNA- pulm nodular amyloidosis, appendicitis or peritonitis, skin infections
Range from narrow to broad
General points with penicillin: MOA
drug resistance
PAPI
4 basic mech
1. Beta lactamase- MC- penicillinase
2. Alteration of PBPs- methicillin resistance- altered pbps
3. Impaired penetration-> Gram Neg only due to impermeable outer mem of cell wall- beta lactamase can enter Gram Neg via porins
4. Active pumping- efflux pump in gram neg
DRUG RESISTANCE
Beta lactamases
100s of them
- Produced by: staphylococcus aureus, H. flu, Escherichia coli
- Extended spectrum B lactamases: AmpC B-lactamase PRODUCED BY PSEUDOMONAS AERUGINOSA AND ENTERO-> HYDROLYZES CEPHALO AND PENICILL
- Carbapenems->mostly res to penicillinases and cephlasporinases-> can hydrolyze metallo-beta lactamases and carbapenemases
typically prefer penicillins to ceph
Pharmacokinetics for Penicillins
- Oral Pen (not amox) = 1-2 hours after eating-> amox doesnt matter
- Serum conc rapidly equilibrate to most tissues EXCEPT EYE, PROSTATE, CNS
- Rapidly exreted by kidneys-> tubular secretions
* Nafcillin = exc hepatic
* Oxacillin, cloxacillin dicloxacillin- renal/hepatic
Pharmacokinetics for Penicillins
- Oral Pen (not amox) = 1-2 hours after eating-> amox doesnt matter
- Serum conc rapidly equilibrate to most tissues EXCEPT EYE, PROSTATE, CNS
- Rapidly exreted by kidneys-> tubular secretions
* Nafcillin = exc hepatic
* Oxacillin, cloxacillin dicloxacillin- renal/hepatic
AE Penicillins
- very safe
- non specific maculopapular rashes
- GI upset in large doses= N/V, Diarr
- Seizures in renal failure= high dose
- TYPE 1 HYPERSENS IS MOST SERIOUS
- Specific:
- Nafcillin= NEUTROPENIA
- Oxacillin, Nafcillin- hepatitis
- Clavulanate- GI symp elderly, hepatitis, cholestasis
Parenteral Penicillins AE
aqueous
Hemolytic anemia
leukopenia
thrombocytopenia/neutropenia
neuropathy
nephropathy
Toxic epidermal necrolysis (TEN)
True Type 1 Hypersensitivity reactions= IgE mediated
Pruritis, Urticaria, Angioedema
N/V, flushing, wheezing, hypotension, anaphylaxis
Streptococcus species
Gram + Cocci
- Streptococcus Pyogenes (Group A strep)
- Streptococcus Agalactiae (Group B strep)
- Streptococcus Pneumoniae (Pneumococcus)
- Viridans Streptococci- Strep mitis, Strep anginous, strep salivarus
Group A strep
- Erysipelas
- Cellulitis
- Necrotizing Fasciitis
- Streptococcal PHaryngitis
- Impetigo
- Rheumatic Fever
Group A strep coccis and Tx
TX: Penicillin G or VK- for most strep infections
Erysipelas- tx depends on s&s of toxicity
* none= oral Penicillin or Amoxicillin
* yes= parental use= Ceftriaxone or Parenteral Aqueous crystalline Penicillin G
Necrotizing fasciitis= Penicillin 4 plus clindamycin
Group B strep sepsis in neonates
Group B strep= GI and genital tracts
Maternal colonization in prego= PRIMARY RISK FACTOR for GBS in neonates
Confirmed during screening: PENICILLIN G 4 IS GIVEN INTRAPARTUM
* ampicillin is alternative or cefazolin if allergic
Diag INFANT= PENICILLIN G IS DRUG OF CHOICE
Cephalosporins overall
- 4 generations based on structures and spectra
- MORes same as Penicillins
- Broader spectrum of coverage vs penicillins
1-4 gen Cephalosporin
- Cefalexin, Cefazolin
- Cefoxitin, Cefuroxine, Cefotetan
- Ceftazidime, Ceftriaxon
- Cefipime
Ceph 1st gen
Cefazolin, Cephalexin
Spectrum: GRAM += Staph and Strep
* activity against: E. Coli-, K pneumoniae, Proteus mirabilis
FDA APPROVED FOR SKIN, SOFT TISSUE, UTIS, RESP TRACT, STREP PHARYNGITIS
Cephalexin-> oral for skin, soft tissue, UTI
Cephazolin-> IV and IM= ANTI STAPH SURGICAL PROPHYLAXIS
Ceph 2nd gen
Cefoxitin, Cefuroxime, Cefotetan
GREATER GRAM - COVERAGE
Cephuroxime- alt for AOM
Cefuroxine and Cefotetan- Anti-Anaerobic activity + pelvic inflam disease, prophylaxis for post opp appendicitis
Ceph 3rd gen
Cefizime, Ceftriaxone, Cefdinir
EVEN GREATER GRAM - CROSS BBB
Spectrum: CEFTAZIDIME ONLY AGENT FOR PSEUDOMONAS AERUGINOSA
some improved staph coverage
Ceftriaxone= MANY INDICATIONS, use for meningitis for empiric coverage
excreted by kidney, require dose adjustment
Ceftrixone uses
1.UTI
2.Uncomplicated Gonorrhea
3.Pelvic Inflammatory disease
4.Meningitis for empiric coverage CROSSES BBB
Ceph 4th gen
Cefepime
hydrolyzed by extended spectrum Beta lactamases
Spectrum: Pseudomonas Aeruginosa, enterobacter,
PENETRATES well into CSF
Indications: Very sick people
Febrile neutropenia- empiric therapy
mod to severe pneumonia
complicated intraabdominal infections
Bacteremia
Cephalosporin/BLactamase inhibitor combo
- Ceftazidime/Avibactam
- Ceftolozane/Tazobactam
Inhibits other beta lactamases
Cephalosporin 5th gen
Ceftaroline
Ceph AE
Allergic reactions: common with penicillin, aminopenicillins, 1 and 2nd ceph
hypersens: anaphylaxis, fever, rashes, nephritis, granulocytopenia
Local irritation
renal toxicity/interstitial nephritis rarely
Seizures in renal insufficiency
Ceph general info
Broader spectrum ceph= greater risk of C. diff diarr
All ceph= renal elim= no dosage adj but MONITOR FOR CKD-> except ceftriaxone= Biliary tract
Meningitis tx that reach csf levels high enough: Ceftriaxone, cefotaxime, ceftazidime, cefepime
Ceph general info
Broader spectrum ceph= greater risk of C. diff diarr
All ceph= renal elim= no dosage adj but MONITOR FOR CKD-> except ceftriaxone= Biliary tract
Meningitis tx that reach csf levels high enough: Ceftriaxone, cefotaxime, ceftazidime, cefepime
Carbapenems
- Imipenem
- Meropenem
- Ertapenem
Carbapenem basics
all parenteral agents
REN ADJUSTING IF RENAL DISEASE
MOA: enter Gram - through porins and bind PBPs
MOR: produce Beta lactamases, efflux pumps, mutations of porins or pbps
Carbapenems: Spectrum of activity
1.Broad spectrum of Activity
2. Gram - organisms-> H flu, N. Gonorrhea, including those that produce extended spectrum beta lactamases
3. Gram + organisms
4. NO ACTIVITY AGAINST MRSA
Imipenem
Carbapenems
Beta lactamase resistant
GOOD AGAINST GRAM NEG RODS
inactivated in pct by dehydropeptidase 1 soooo ADD Cilastatin to inhibit
* cause seizures in those with renal failure in high amounts
* GOOD TISSUE PERF INCLUDING CSF
AE: GI, rash, site reactions
Meropenem and Ertapenem
dont spend alot of time on
Meropenem= no need for Cilastatin, for bacterial meningitis, greater act against neg but less pos than imipenem
Ertapenem= not fo pseudomonas, long half life
Antibiotics that target the cell wall and cell membrane
1.Beta lactams
2.Glycopeptides-> Vancomycin
3.Daptomycin
Glycopeptide->Vancomycin
MOA: inhibits cell wall biosynth-> blocks glycopeptide polymerization
MOR: produce D-ala-D-lactate dipsipeptide which thwarts vanc
Excretion: RENAL CLEARANCE = MARKED DOSE ADJ FOR RENAL FAILURE
SE: rash, thrombocytopenia, bullous dermatitis, nephro/ototoxic rare, RED MAN SYNDROME- flushing caused by rapid infusion due to release of histamine
Vancomycin indications
NO GRAM - COVERAGE
Positive: for sensitive staph aureus, enterococcus, bacteremia and endocarditis caused by MRSA
+ aminoglycosides for serious inf
CLOSTRIDIOIDES DIFFICILE INFECTION
Daptomycin
targets cell wall and cell membrane
MOA: binds to cell mem via calcium dependent insertion of the lipid tail-> potassium efflux= cell death
Spectrum: GRAM + : MRSA, MSSA, VISA, VRSA
Indications: serious bacterial skin infections by +, bacteremia or endocarditis caused by S. AUREUS STRAINS AND MRSA
Daptomycin AE
- Eosinophilic pneumonia: 2-4 wks after therapy start
- DRESS syndrome: angioedema, drug rash w/ eosinophilia, systemic symptoms
- Myopathy/Rhabdomyolysis: Creatinine Phosphokinase CPK should be monitored WEEKLY during therapy
Empiric tx for common skin and soft tissue infections (SSTI)
Purulent (abscess, furuncle, carbuncle, cellulitis with purulence)-> staph aureus is common-> 1. drain 2.Cephalexin or Clindamycin if mrsa 3. extensive= cefazolin low mrsa concern or Vancomycin/daptomycin if mrsa
Non purulent (cellulitis, erysipelas)-> Beta hemolytic strep-> 1.Cephalexin, amox, clindamycins or IV cefazolin or vancomycin
Antimetabolites
- Sulfonamides
- Trimethoprim
- Trimethoprim-sulfamethoxazole (TMP-SMX)
Sulfonamides
Topical: Silver Sulfadiazine-> burn tx
Oral: Sulfamethoxazole or Sulfadiazine and Pyrimethamine (acute toxoplasmosis)
General: GRAM POS AND NEG
MOA: inhibits Dihydropteroate Synthase-> INTERRUPTING FOLATE
Sulfonamides AE
Hematologic effects: Megaloblastic anemia or hemolytic/aplastic anemia
photosens
stevens johnson syndrom
DO NOT GIVE TO NEONATES UNDER 3 MONTHS OR MOMS AT END OF PREGO-> increase unconjugated bilirubin and increase kernicterus in fetus (brain damage)
CANT GIVE TO SULFA ALLERGY OR PORPHYRIA
Trimethoprim
MOA: interrupt human folate metabolism-> prevent tetrahydrofolic formation
MOR: point mutations in DHFR structural gene
Trimethoprim-sulfamethoxazole
bactrim
RUGS
Indications:
r- Respiratory tract infections
u-uti
g-GI infections
s-Skin infections- MRSA
Contraindications:
sulfa allergy
AVOID IN PREGO DUE TO EFFECT ON FOLIC ACID METAB
AE: STEVENS JOHNSON SYND, HYPERKALEMIA-> BLOCK OF THE COLLECTING TUBULE SODIUM CHANNEL, HIV + HIGHER CHANCE OF RXN
Erythema Multiforme, Stevens Johnson Syndrome, Toxic Epidermal Necrolysis
- Erythema multiforme-> target lesions, oral lesions, hands forearms
- Stevens Johnson Syndrome- kids, uri like prodrome, MOST DUE TO DRUG REACTIONS, MORE THAN 2 MUCOSAL SITES, admit to burn center
- Toxic epidermal necrolysis- elderly, HIV increased risk, mucous mem, BURN CENTER
Stevens Johnson Syndrome
test question
1.Rare
2.RF: Drugs, mycoplasma, CMV
3.start: fever, flu like symp
4.Then: blistering->skin, mucous mem, urogenital tract
5.Difficulty: breathing, swallow, urinating
6.LIFE THREATENING
7.BARRIER LOSS CAUSES FLUID LOSS AND INCREASE SUSCEP TO INFECTION/SEPSIS
Antimetabolite indications
1.Sulfonamides- topical for sepsis, ORAL= ACUTE TOXOPLASMOSIS
2.Trimethoprim- conjunctivitis
3.Bactrim (TMP/SMX)- UTI, skin infections
Antimetabolite indications
1.Sulfonamides- topical for sepsis, ORAL= ACUTE TOXOPLASMOSIS
2.Trimethoprim- conjunctivitis
3.Bactrim (TMP/SMX)- UTI, skin infections
Fluoroquinolones names
- Ciprofloxacin
- Levofloxacin
- Ofloxacin
- Moxifloxacin
- Gatifloxacin
Fluoroquinolones general
MOA: directly inhibit bacteria DNA
MOR: site mutations, plasmid= target mimics, Resistance increases the duration of therapy
Route: oral
Excretion: Renal clearance, adjust for GFR
Spectrum coverage: Gram -, Gram +, intracellular and poorly staining organisms-> pseudomonas coverage
Fluoroquinolones indications
Ciprofloxacin-> Gram - with Pseudomonas: conjunctivitis, anthrax, otitis externa
Levofloxacin-> COMMUNITY ACQUIRED PNEUMONIA, better gram +
Ofloxacin-> conjunctivitis
Moxifloxacin->comm acquired pnemonia, better gram + coverage
Ciprofloxacin
GOOD FOR PREGO AND POST EXPOSURE ANTHRAX
CHILDREN WITH COMPLICATED UTIs
cipro plus levofloxacin= approved for children for post exposure to inhalation of anthrax or the plague
TX for acute bacterial conjunctivitis
COTE
Empiric approach:
1. Erythromycin
2. Trimethoprim drops
3. Ofloxacin opthalmic drops
4. Ciprofloxacin drops
