Week 4: antibiotics Anti-Bacterial Agents: Cell Wall Synthesis Inhibitors Flashcards
What are characteristics of Anaerobes?
Grow only in the absence of O2
Found in oral and GI tract and vagina
Most anaerobes are medically important to know
Cause diseases when normal mucosal barriers do not function normally
Can be classified as gram negative vs positive
What color are gram positive vs gram negative microbs and why?
Gram positive are purple
Gram negative are pink since when cleaned with ethanol it becomes clear
Broad spectrum vs narrow spectrum bacteria
broad: effective against multiple organisms from more than a single class, more likely to disrupt normal flora, risk of superinfection by a second organism
narrow: effective against limited number of organism, unlikely to disrupt normal flora
bacteriostatic vs bactericidal?
bacteriostatic: capbale of inhibiting growth or reproduction of bacteria, does not kill them.
bacterialcidal:
capable of actively killing bacteria, 99.9% killing within 18 to 24 hours in lab condition
MIC (Minimum inhibitory concentration)
:the lowest concentration of antibiotics that inhibits bacterial growth
MBC (Minimum bactericidal concentration):
Lowest concentration of antibiotics that kills 99.9 % of bacteria
Cell Wall Synthesis Inhibitors
Beta Lactams -Penicillin -Cephalosporins -Carbapenems -Monobactams Beta-Lactamase Inhibitors Vancomycin Others
What is Atypical bacteria?
An inexact term applied to bacteria which are particularly “unusual” in structure, morphology, biochemistry, or life cycle.
Gram positive
Cocci
Staphylococcus aureus
Streptococcus
Enterococcus
Gram positive
Rods
(Corney
Mike’s list of basic cars)
Corneybacterium Mycobacteria Listeria Bacillus Nocardia
Gram positive
Anaerobes
(CLAP)
Clostridium
Lactobacillus
Actinomyces
Propionibacterium
Gram negative
Aerobes:
Neisseria meningitidis (Meninogococcus)
Neisseria gonorrhoeae
Anaerobes: Haemophillus influenzae Escherichia coli (E. coli) Klebsiella pneumoniae Proteus mirablilis Pseudomonas aeruginosa Moraxella catarrhalis
Atypicals
Mycoplasma pneumoniae : Walking pneumonia
Chlamydia trachomatis & pneumoniae: PID, STD , pneumonia
Rickettsia : Rocky mountain spotted fever, typhus fever
Legionella :Legionnaires’ disease (severe pneumonia)
Enterococci
UTI, bacteremia, endocarditis, meningitis
strep pnumoniae
sepsis, pneumonia, meningitis, middle ear infection in children, sinusitis
Group B strep
sepsis, pna, meningitis in newborns, mostly not harmful, natrually comes and goes in our body,mild idsease UTI, vaginitis,
group A strep (s.pyogenes)
strep throat, rheumatic fever, post-streptococcal glomerulonephritis, impetigo, sinusitis, cellulitis, necrotizing fasciitis
Gram Positive: Clostridium Difficile risk factors
Diarrhea to life threatening inflammation of colon
older adults in hospital or nursing homes
after abx use
Gram Positive: Clostridium Tetani risk factors
tetanus
Gram Positive: Clostridium Perfringens risk factor
most common causes of food poisoning
Gram negative: Pseudomonas
UTI, respiratory, soft tissue infection, GI infection, sepsis, usually form hospitalized patients
Gram Negative: Hemophilus influenzas
Gram negative: escherchia coli
most strain is not harmful, diarrhea, UTI
Gram Negative: Kiebsiella Pneumoniae
mostly not harmful, lives in GI and feces normally, can cause pneumonia, UTI, cellulitis, etc
Gram negative: moraxella catarrhalis
normally present in oropharynx, skin and genital area, could cause conjunctivitis, upper and lower respiratory infection in kids and adults
Gram negative: shigella and salmonella
shigellosis-diarrhea, fever, stomach cramp, salmonellosis
inhibitors of metabolisms
sulfonamides, trimethoprim
inhibitors of cell wall synthessis
Beta-lactams, daptomycin, fosfomycin, lipoglycopeptide, vancomycin
inhibitors of protein synthesis
ahminoglycosides, chloramphenicol, clindamycin, macrolides, oxazolidinone, tetracyclines
inhibitors of cell membrane function
amphotericin B, isonizaid, polymyxins
inhibitors of nucleic acid function or synthesis
fluoroquinolones, rifampin
Penicillin
PCNs: 1st Antibiotic: 1928
For Streptococcal and staphylococcal infections
Synthetic PCNs: Developed to overcome resistance issues
Classified based on the spectrum of activity
Have both narrow and broad spectrum
What is the penicillin class/clinical indication?
Narrow and Broad spectrum
Time-dependent bactericidal
Effective for Gram-positive organisms : Upper /Lower respiratory . UTI, STIs, Endocarditis
Extended spectrum PCNs: Pseudomonas (G -)
Penicillin pharmacokinetics
Oral formulations are acid-stable
PO absorption is inhibited by co-ingestion of food
Widely distributed
Penetrate CSF in presence of inflammation ( penicillin can cross BBB well without inflammation)
Excreted by kidneys
Dosage adjustment with impairment
Prolonged effects by administration with Probenecid by inhibiting tubular secretion
Half-life is typically 30 – 90 minutes
What are drawbacks of penicillin?
Seizure activity: high-dose with renal impairment
Rare: leukopenia, thrombocytopenia and hemolytic anemia
Allergic reactions:
Urticaria to hemolytic anemia and anaphylaxis,
Assume cross-reactivity throughout class,: 10% of persons who are allergic to PCN are also allergic to Cephalosporins
GI Disturbances:
N/D caused by oral
medications via direct irritation or over growth of G+ organisms or yeast;
Ampicillin implicated in pseudomembranous colitis
Drug Interaction
Rare
What are action of resistance in penicillin?
β-lactamase produced by bacteria cause enzymatic hydrolysis of the B-lactam ring, resulting in loss of antibacterial activity
Cephalosporins
Structurally similar to PCNs
“Generations”
Based on spectrum of activity
1st → 5th : increase in gram (-) coverage and loss of gram (+) activity
What class are Cephalosporins?
- Time-dependent bactericidal effect
- Gram positive to Gram negative
- newer generation covers more gram negative
Cephalosporins pharmacokinetics?
A: IV and PO,
Well-absorbed from GI tract
Food may enhance absorption
D: Most 1st & 2nd –generation do not cross BBB, even with inflamed meninges
M: Cephalosporins with side chains may undergo hepatic metabolism
E: Majority excreted unchanged in urine via active tubular secretion; EXCEPT
cefoperazone and ceftriaxone, which are mainly excreted in bile
What are drawback of Cephalosporins
Safe with favorable toxicity profile Allergic Reactions: 5-15% of persons allergic to PCN are also allergic to cephalosporins Anaphylaxis Fever Skin rash Nephritis Granulocytopenia Hemolytic anemia Other reactions: MT sidechain causes hypoprothrombinemia and inhibits aldehyde dehydrogenase (can cause disulfiram-like reaction with ETOH ingestion) Local irritation at injection site Drug Interaction Rare May ↑ aminoglycoside toxicity Probenecid & loop diuretics Increases half-life of some cephalosporins, inhibiting tubular secretion
What are action of resistance for Cephalosporins?
Less than seen with PCNs due to more stable β-lactam ring
Via production of β-lactamase
Via decreased membrane permeability to cephalosporins
Via mutation in the binding site on cell membrane
What are the First generation of Cephalosporins and spectrum of activity
-cefazolin, cefadroxil, cephalexin
-Best for G + cocci
G – (P. mirabilis, E coli, K. pneumoniae)
Susceptible to B-lactamase
Does not cross BBB
-
First generation of Cephalosporins clinical use and indication
Skin Infections
Pneumococcal respiratory infections
UTI
Surgical Prophylaxis
What are the second generation of Cephalosporins and spectrum of activity
Cefaclor Cefprozil Cefuroxime sodium Cefuroxime axetil Cefotetan/Cefoxitin ----- Extended G – coverage (H. flu) Less activity against G+ organisms than 1st Generation Does not cross BBB
Second generation of Cephalosporins clinical use and indication
CAP
Respiratory infections
Skin infections
What are the third generation of Cephalosporins and spectrum of activity
Cefdinir
Cefixime
Cefotaxime
Ceftazidime/Ceftriaxone
—–
Active against G- bacilli (H. flu, Meningococcus)
May be useful for G + infections (Pneumococcus)
Third generation of Cephalosporins clinical use and indiciations
Generally reserved for serious infections (i.e. Bacterial meningitis)
PCN-resistant Neisseria gonorrhoeae infection
Pseudomonas
Lyme disease
What are the fourth generation of Cephalosporins and spectrum of activity
Cefepime
G+ activity of 1stGeneration
Active for G- organisms as 3rd generation
More resistant to β-lactamases produced by G- organisms
Does cross BBB
Fourth generation of Cephalosporins clinical use and indiciation?
Better or infections caused by Beta-lactamase-producing G- organisms: Enterobacter, Haemophilus, Neisseria,
Pseudomonas, nosocomial bacterial infection
In general, administer with other agents(aminoglycosides) to prevent resistance
As the generation increases, so does the potency and spectrum, esp. against G- species
What are the fifth generation of Cephalosporins and spectrum of activity
Ceftaroline
Broad spectrum
Does not cross BBB
Fifth generation of Cephalosporins clinical use and indications
MRSA
Beta-Lactamase Inhibitors
Prevents the breakdown of the beta-lactam ring by beta lactamase producing the bacteria
But NO significant antibacterial activities or cause side effects
Usually used as combination drugs
Bacteria can produce penicillinases or beta-lacatmases 🡪 Inactivate PCN and cephalosporines
Beta-Lactamase Inhibitors class/clinical indications
Broad spectrum
Intraabdomen and GYN infections
Skin & Soft tissue infection: human and animal bites
Diabetic foot infections
Respiratory track aspiration: pneumonia sinusitis abscess
Beta-Lactamase Inhibitors pharmacokinetics
Penetrates most body tissues
Exception: CNS/Brain
Elimination: glomerular filtration: renal dysfunction & dialysis necessitate dosage change
Beta-Lactamase Inhibitors action of resistance
- Bacteria produce β-lactamase → breaks down β-lactam → penicillin inactive
- Diminishes cell wall permeability to drug
- Via mutation in the binding site on cell membrane
Vancomycin
cell wall synthesis inhibitor, bactericidal, mostly gram positive (including MRSA) but covers gram negative for c.diff
serum concentration needed for IV
Which generation achieves therapeutic level at CSF for cephalosporin?
3rd generation
which generation of cephalosporin treats MRSA?
5th generation
Which PCN have pseudomonas coverage?
ampicillin, amoxicillin
