Antibiotics Lecture 2 Flashcards
Cephalosporins 1st generation
- Cephalexin- oral*
* Cefazolin- IV*
Cephalosporins 2nd generation
- Cefuroxime- oral*
* Cefoxitin- IV*
Cephalosporins 3rd generation
- Cefpodoxime- oral**
* Ceftriaxone- IV**
Cephalosporin 4th generation
• Cefepime- IV
Cephalosporin activity
Cephalosporins are less susceptible to β- lactamases giving them a broader spectrum of action compared to penicillins including Staphylococcus
In general, earlier generations have better Gram positive coverage than later generations*
In general, later generations have better Gram
negative coverage than earlier generations*
Common uses of Cephalosporins 1st generation
UTI, pharyngitis, mild skin or soft tissue infections, upper and lower respiratory tract infections
Common uses of Cephalosporin 2nd generation
Sinusitis, pharyngitis, otitis media, lower respiratory tract infections Cefuroxime- lyme disease
Cefoxitin and cefotetan also have anaerobic coverage (Bacteroides fragilis)
Common uses of Cephalosporin 3rd generation
Community acquired pneumonia, otitis media, upper respiratory tract infections, meningitis, febrile neutropenia,
Ceftazidime has coverage against Pseudomonas aeruginosa
Common uses of Cephalosporin 4th generation
Meningitis, febrile neutropenia, pneumonia, nosocomial infections, pyelonephritis
Adverse Reactions of Cephalosporin
- Cefixime- highest incidence of GI effects
- Cefprozil- lowest incidence of diarrhea
- Cefaclor-highest incidence of rash
- Cefotetan- has MTT side chain that can cause hypoprothombinemia and bleeding as well as a disulfiram like reaction ***
Special Considerations of Cephalosporin
Monitoring
• renal function
• Food
• Take with food- Cefaclor ER, cefuroxime suspension, cefditoren,
cefpodoxime tablets • Drug interactions
• Probenicid may increase concentrations of cephalosporins
• Use with caution in patients with a PCN allergy**
Cross sensitivity in penicillin allergic patients
Overall rate of allergic reactions to cephalosporins is 1%
Initial reported rate of cross sensitivity (10%) may have
been overestimated. It is believed that early cephalosporin antibiotics may have contained trace amounts of penicillin. Actual rate is ~ 3-7%
Patients are at higher risk of having a reaction with a first generation cephalosporin
Patients with a positive PCN skin test seem to be at higher risk. There is no skin test for cephalosporin allergy.
Monobactams MOA
Aztreonam
MOA: Bind to penicillin binding protein and inhibit cell wall synthesis which leads to cell death
Aztreonam
• Only monobactam available in the USA
• Has only Gram negative coverage including Pseudomonas; no Gram positive or anaerobic coverage
• Good for resistant infections b/c it is resistant to many
beta-lactamases produced by Gram negative bacteria
• No cross sensitivity with PCN or cephalosporin allergy
• IV or IM administration
• Doses must be adjusted for decreased renal function
• Low incidence of adverse effects -diarrhea
Carbapenems MOA
Imipenem/ cilastatin Meropenem Doripenem Ertapenem MOA: Bind to penicillin binding protein and inhibit cell wall synthesis which leads to cell death
Carbapenems
• Resistant to most beta-lactamases and are the drugs of choice for infections caused by ESBLs- extended spectrum beta- lactamases**
• Covers Streptococcus, Staphylococcus, Listeria, Gram negatives, and anaerobes; All cover Pseudomonas except ertapenem
• Doses must be adjusted for decreased renal function
• Cross sensitivity with PCN allergy- similar rate as cephalosporins***
• Adverse effects- nausea/vomiting, seizures (highest incidence with imipenem in patients with renal failure)
• Clinical uses include urinary tract and lower respiratory
infections; intra-abdominal and gynecological infections; skin, soft tissue, bone, and joint infections
• Imipenem is combined with cilastatin to prevent breakdown by renal dihydropeptidase.
Glycopeptide antibiotics
Vancomycin Telavancin
MOA: prevents cross-linking of the cell wall peptidoglycan during cell wall synthesis
works on the cell wall and leads to cell death
Vancomycin IV / PO
Gram positive coverage only
Used for MRSA infections- sepsis, endocarditis, meningitis, skin/ soft tissue infections
Oral dosage form is not absorbed- used for treatment of C. difficile only
Dosing for vancomycin is variable- based on actual body weight and renal function- most hospitals have dosing protocols run by pharmacists
Monitoring of serum levels is generally performed- trough should be above 10 mcg/ml to prevent resistance; goal- 10-20mcg/mL Adverse reactions- ototoxicity (sometimes permanent), nephrotoxicity (rare), injection site reaction
Risk of nephrotoxicity increased when other nephrotoxic drugs are administered with vancomycin (amino glycosides)
Vancomycin- Red Man syndrome
Infusion related reaction that is caused by the release of histamine
May cause erythematous or urticarial reactions, flushing, tachycardia, and hypotension.
This is not an allergic reaction
Management: stop the infusion, wait for it to subside then, slow the infusion rate down (infusion should be no faster than 1gm/ hr, but may need to be longer if Red Man syndrome occurs), may administer Benadryl prior to infusion
Telavancin
Similar to vancomycin, but is once daily dosing
Black box warning in pregnancy-may cause abnormal fetal development. Perform pregnancy test in women of child bearing age
Indicated for complicated skin and soft tissue infections. Investigational in nosocomial pneumonia
Dose must be adjusted for renal function
In clinical trials more patients experienced adverse reactions with telavancin compared to vancomycin
ADRs-Red Man syndrome;must infuse over at least 60 min., nephrotoxicity, GI upset, metallic taste.
Other cell wall or membrane active agents
daptomycin fosfomycin bacitracin cycloserine
Daptomycin (IV)
• Spectrum of activity is similar to vancomycin but it also covers vancomycin resistant enterococci (VRE) and vancomycin intermediate and resistant S. aureus (VRSA)
• Used for skin/soft tissue infections, bacteremia, endocarditis (not pneumonia!!)
• Doses must be adjusted for decreased renal function
• Adverse effects- injection site reaction, fever, chills,
diarrhea, nausea/vomiting
• Muscle cramps and weakness may occur- must monitor
CPK and discontinue drug if muscle pain and elevation of CPK > 5 times ULN occurs
Fosfomycin
oral formulation with Gram negative and Gram positive coverage. Used for UTIs in women, given as one time 3 gram dose.
Bacitracin
highly nephrotoxic when administered IV so it is only used topically. Used to treat surface lesions on skin or irrigation of wounds, joints
Cycloserine
covers Gram positive and Gram negative but is mainly used for treatment of resistant tuberculosis
Protein Synthesis Inhibitors- Tetracyclines (3)
Tetracyclines
• Tetracycline • Minocycline • Doxycycline
MOA of Tetracyclines
Tetracyclines bind to the 30 S ribosomal subunit, which prevents binding of tRNA to the mRNA- ribosome complex, thus interfering with protein synthesis
Tetracyclines common uses
Respiratory infections, community strains of MRSA (CA-MRSA), acne
Doxycycline- anthrax, chlamydia, lyme
Adverse Effects of Tetracyclines
• GIintolerance
• Photosensitivity
• Toothdiscolorationandabnormalbone
growth
• Do not use in second half of pregnancy or children <8 years old
Vestibular toxicity with minocycline
– dizziness, ataxia, nausea and vomiting- disappears within 24-48 hours after drug is discontinued
Special Considerations of Tetracyclines
Administration must be separated from food containing aluminum, magnesium, calcium, and iron by at least 1-2 hours
Food
• Minocycline: with or without
• Tetracycline: empty stomach
• Doxycycline: take with food due to GI intolerance (
absorption up to 20%) Monitoring
• Renal, hepatic, CBC, hematologic with long term use
tigecycline
• Glycylcycline antibiotic, Derivative of minocycline
• Covers Gram positive, Gram negative and anaerobes
• Indicated for complicated skin and skin structure infections and
complicated abdominal infections; has failed to demonstrate efficacy in hospital acquired pneumonia but is indicated for community acquired pneumonia.
• Has efficacy vs. MRSA, MRSE (staph epidermidis), VRE, and penicillin resistant Streptococcus pneumoniae.
• Has also shown efficacy against other multi-drug resistant organisms
• Phase 3 and 4 clinical trials have shown and increase in all cause mortality- mainly used for salvage therapy
