Antimicrobials Flashcards
Define postantibiotic effect.
Killing action of microorganisms continues once drug plasma levels have fallen below a measurable level.
Define minimal inhibitory concentration (MIC).
Lowest concentration of antibiotic that prevents visible growth. Usually measured y broth/tube dilution or disk sensitivity
Define minimal bactericidal concentration (MBC).
Lowest concentration of antibiotics that result in a 99.9% decline in colony count after overnight broth dilution incubations. The MBC of a truly bactericidal agent is equal to or just slightly above its MIC value.
Define empiric therapy.
Tx without known exact microorganism due to time sensitive pathology (ex. meningitis). Choice of drug is influenced by site of infection or patients history. Frequently, broad spectrum therapy is used in the initial tx of serious infections.
General complications of Abx therapy?
- hypersensitivity
- direct toxicity
- superinfection - new or secondary infection that occurs during antimicrobial therapy of primary infection
Basic features of Penicillin.
Bactericidal, inhibits last step in peptidoglycan synthesis by binding to penicillin-binding protein [bacterial enzyme that penicillin binds to inactivate replication]. Binding to PBP is determined by the size, charge and hydrophobicity of the penicillin Abx. [PCN can easily cross cell wall of Gram positive bacteria, but use porins within gram-negative bacteria making it more selective] PBP mutations can lead to Abx resistance. Because these drugs target the peptidoglycan synthesis, they are only active against organisms with peptidoglycan cell walls [they are INEFFECTIVE against mycoplasma, protozoa, fungi, viruses]. Bacteria also produce autolysin to mediate cell lysis - Penicillins activate autolysins initiating cell death.
Half-life = 30-60 minutes (except repository PCNs which have a long effect)
Oral absorption - impaired by food, except amoxicillin which has high oral bioavailability and Nafcillin which is erratic so is not suitable for oral admin
Nafcillin, Ampicillin, peperacillin - high levels in bile
Poor CSF penetration and insufficiency levels in prostate and eye.
PCN excretion - via kidneys so do not administer to pt with kidney failure
Oxacillin and dicloxacillin - renal and biliary excretion
Nafcillin - primary excretion in bile
Penicillin G?
Penicillin G = Benzylpenicillin
Natural penicillin, given via IV, binds PBP in bacteria to inhibit cell wall synthesis. There is increased resistance due to inactivation by B-lactamase secreted by bacteria that breaks down B-lactam ring in the PCN structure making it inactive.
Active against most gram positive cocci (NOT STAPH), gram positive rods, gram negative cocci and most anaerobes.
Drug of choice:
- Syphillis
- Strep infection (Rheumatic fever prophylaxis)
- susceptible pneumococci
Repository penicillins?
Penicillin G Procaine AND Penicillin G Benzathine
These drugs were developed to prolong the duration of PCN G. They are effective against mainly gram positives (not staph species). Same as PCN G, except delivered via IM NOT IV.
Penicillin G Procaine - IM, half life of 12-24hrs, increased resistance, so is seldomly used
Penicillin G Benzathine - IM, half life of 3-4 weeks
Drug of choice:
- syphilis
- rheumatic fever prophylaxis (strep infection)
Penicillin V?
Natural penicillin, given orally as it is more acid stable than PCN G. It is a bactericidal drug that binds the PBP and inhibits the cell wall synthesis.
Drug of choice:
STREP THROAT– given orally for mild to moderate infections (pharyngitis, tonsilitis, and skin infections caused by Strep)
Anti-staphylococcal PCN?
Methicillin Nafcillin Oxacillin Dicloxacillin [M,N,O,'P'(D)]
Methicillin, Nafcillin, Oxacillin, Dicloxacillin?
Anti-staphylococcal PCN that are B-lactamase resistant (therefore are not broken down by the B-lactamase enzyme) but are inactive against MRSA organisms. These Abx are restricted to treatment of B-lactamase-producing STAPHYLOCOCCI.
Drug of choice:
Staphylococci ENDOCARDITIS in pts without artificial heart valves
*Methicillin is no longer FDA approved as it lead to interstitial nephritis
AE Dicloxacillin - Hypersensitivity / GI / Secondary infections
AE Oxacillin - Hypersensitivity / GI / Hepatitis / Secondary infections
AE Nafcillin - Hypersensitivity / GI / Neutropenia / Secondary infections
Ampicillin and Amoxicillin?
Extended-spectrum penicillins that are similar to Penicillin G, but have enhanced GRAM NEGATIVE activity. They are susceptible to B-lactamases, so generally need to be given with B-lactamase inhibitors.
Amoxicillin has high oral bioavailability compared to other PCNs (including ampicillin) and is prescribed for children and during pregnancy. [Amoxicillin is given orally whereas Ampicillin is given oral, IV or IM]
Used to treat….
- Acute otitis media
- Streptococcal pharyngitis
- pneumonia
- skin infections
- UTIs
* *upper respiratory infections (H. flu and S. pneumo)
Amoxicillin - drug of choice for endocarditis prophylaxis during dental or respiratory tract procedures (ex. protect against Strep viridan driven endocarditis post dental procedure)
AE [Ampicillin] - Hypersensitivity / GI / Maculopapular Rash / Pseudomembranous colitis
AE [Amoxicillin] - Hypersensitivity / GI / Maculopapular Rash / Secondary infections
What drugs are used to treat enterococci and listerial infections?
Ampicillin+aminoglycoside
What drugs are used as prophylactic tx of dog, cat and human bites?
Amoxicillin+Clavulanic
What drugs are used as endocarditis prophylaxis during dental or respiratory procedures?
Amoxicillin
“Anti-pseudomonal” PCNs?
Carbenicillin
Ticarcillin
Piperacillin
*Piper saw a Tic on the Car
Carbenicillin, Ticarcillin, Piperacillin?
Antipseudomonal PCNs that bind the PBP in bacteria inhibiting cell wall/peptidoglycan synthesis. These PCNs are effective against most Gram-negative and gram-positive bacteria and are often combined with B-lactamase inhibitors as they are susceptible to B-lactamase secreted by the bacteria.
Drug of choice:
- Pseudomonas aeruginosa as injectable treatment (gram negative)
- tx of moderate to severe infections
Penicillin with Aminoglycoside?
These medications have synergistic effects. The PCN facilitates movement of aminoglycosides through the cell wall. When administered, they should NEVER be placed in the same infusion fluid as they form inactive complexes. Therefore need to be given at the same time in separate vial/IVs.
Effective empiric treatment for INFECTIVE ENDOCARDITIS.
What are the 4 mechanisms which PCNs acquire resistance?
- inactivation by B-lactamase
- modification of target PBPs [ex MRSA - altered target PBPs that have low affinity for B-lactam Abx]
- impaired penetration of drug to target PBPs
- Increased efflux
Discuss the Hypersensitivity reaction seen with PCN.
Penicilloic acid - major antigenic determinant
maculopapular rash leading to anaphylaxis
Cross-allergic rxn b/t B-lactam Abx
What AE are seen with PCN and with which ones specifically?
- GI disturbance
- Pseudomembranous colitis - ampicillin
- maculopapular rash - ampicillin, amoxicillin
- Interstitial nephritis - methicillin
- neurotoxicity - epileptic pts at risk
- hematologic toxicities - ticarcillin
- neutropenia - nafcillin
- Hepatitis - oxacillin
- positive coombs test - PCN G and V
- secondary infection - vaginal candidiasis
B-lactamase inhibitors?
Clavulanic acid, Sulbactam, Tazobactam
Contains B-lactam ring but does not have significant antibacterial activity. It binds to and inactivates B-lactamases and is given with PCNs that are susceptible to bacterial B-lactamases.
Basic characteristics of cephalosporins.
B-lactam antibiotics that bind PBP of bacteria and act as bactericidals – this is the same MOA as PCNs as they are also affected by similar resistant mechanisms.
1st generation to 3rd generation - decreasing activity on gram positives and increasing activity on gram negatives
4th generation - gram positive cocci activity and gram negative bacilli activity
5th generation - similar to 3rd as they have increased gram negative activity but they are unique as they have activity against MRSA [generations 1 through 4 are inactive against MRSA]
All are excreted by the kidneys except ceftriaxone (3rd generation) and cefoperazone (3rd generation) which are eliminated by the bile.
General AE - allergic reaction due to cross reaction with PCNs (you can give to pts with mild PCN allergy, but not severe), there may be pain at infection site (IM) or thrombophlebitis (IV), superinfections, and kernicterus (pregnancy)
What microbes are cephalosporins inactive against?
CALL ME
Chlamydia
Acinetobacter
Listeria
Legionella
Mycoplasma
Enterococci
1st generation Cephalosporins?
Cefazolin, Cephalexin
Cefazolin and Cephalexin?
1st generation cephalosporins - substitutes for PCN G and resistant to staphylococcal penicillinase
Active against - GRAM POSITIVE cocci, P. mirabilis, E. coli, K. pneumoniae
Cefazolin - parenteral only
Cephalexin - Oral
AE - HSN and superinfections
*RARELY the drug of choice for any infection – only time is it the rug of choice is Cefazolin for surgical prophylaxis
What is the drug of choice for surgical prophylaxis?
Cefazolin (first generation cephalosporin) - as gram positives might enter the skin during surgery
2nd generation cephalosporins?
Cefaclor
Cefoxitin
Cefotetan
Cefamandole
-ceFAC-, ceFOX-, ceFOT-, ceFAM-
Cefaclor, Cefoxitin, Cefotetan, Cefamandole?
2nd generation cephalosporins that have extended gram-negative coverage from the already gram positive coverage seen with 1st generation. They have increased activity against H-. influenza, Enterobacter aerogenes, and some Neisseria species.
Weaker activity against gram positive organisms which is what 1st generations target. Does a good job, but is NEVER really the drug of choice - can cover wide range of microbes and infections.
Used in the tx of…
- sinusitis
- otitis media
- lower respiratory tract infections
- prophylaxis and therapy of abdominal and pelvic cavity infections [Cefotetan and Cefoxitin]
*Cefotetan and Cefamandole - contain methyl-thiotetrazole groups therefore can cause hypoprothrombinemia (give vit K1 admin to prevent) and disulfram-like reactions (therefore avoid alcohol)
3rd generation cephalosporins?
Ceftriaxone Cefoperazone Cefotaxime Ceftazidime Cefizime
Ceftriaxone Cefoperazone Cefotaxime Ceftazidime Cefizime
3rd generation cephalosporins that have enhanced activity against gram negative cocci [esp. enterobacteriacae, Neisseria, H. flu]. These drugs are less active against gram positives compared to the 1st and 2nd generations.
Cefotaxime and Ceftriazone = usually active against pneumococci
Ceftriazone can also be used as prophylaxis or meningitis in exposed pts, for gonorrhea and meningitis due to ampicillin-resistance H. flu, and tx of Lyme disease (CNS or joint infections).
Cefaperazone and Ceftazidime - activity against P. aeruginosa
All are given parenteral except Cefizime which is administered orally. AE include HSN rxns and superinfections. Cefoperazone also has increased risk of hypoprothrombinemia and disulfram-like reactions. Do not give these to pts with B-lactam allergy as there is partial cross-reactivity with PCNs.
**3rd generations are the only ones that can reach adequate levels int he CSF which is why they are used as treatment and prophylaxis of meningitis
What is the drug of choice for gonorrhea?
Ceftriaxone
What is the drug of choice for meningitis due to ampicillin-resistant H. flu?
Ceftriaxone
4th generation cephalosporin?
Cefipime
Cefipime?
4th generation cephalosporin that is active against a wide antibacterial spectrum. It has the activity of 1st generations against gram positive and the activity of 3rd generations against gram negatives. It is ONLY administered parenterally.
Tx - infections with susceptible organisms [UTIs, complicated intra-abdominal infections (b/c you know these will most likely contain gram positives and gram negatives), febrile neutropenia]
AE - HSN rxns, superinfections, partial cross-reactivity with PCN so do not give to someone who has severe PCN allergy
5th generation cephalosporin?
Ceftaroline
Ceftaroline?
5th generation cephalosporin that has activity against MRSA as well as similar activity to 3rd generation cephalosporins. Just like the 4th generation, the 5th is administered parenterally only.
Used to treat.. skin and soft tissue infections due to MRSA particularly if gram-negative pathogens are coinfecting. It can also be used to treat community-acquired pneumonia when the first line agents are unsuccessful.
AE - HSN rxns, superinfections, partial cross-reactivity with PCN so do not give to someone who has severe PCN allergy
