Infectious Diseases part 1 Flashcards
Fourth generation Cephalosporins
Cefepime (Maxipime) IV
Further expanded gram-neg coverage
Same + pseudomonas aeruginosa
Very commonly used for serious HAI
Concern for seizure if not dosed properly
Second Generation Cephalosporins
Cefuroxime (Ceftin) PO/ IV
Cefoxitin (Mefoxin) IV
Enhance gram-negative activity
Spectrum: Streptococcus, MSSA, enteric GNR, Haemophilus
Cefoxitin has anerobic gram-negative activity
Class less commonly used
Clinical use: De-escalation when cultures are back, prophylaxis for abdominal surgeries
Vancomycin (Vancocin) – IV, PO
MOA: inhibits cell wall synthesis
Spectrum: gram-positive only, drug of choice for MRSA
Given IV for systemic infections including pneumonia, CNS, UTI, bone, blood
Given PO for C diff associated diarrhea
Use the IV formulation and compound an oral solution
Also available as commercially made capsules, but very expensive
MUST monitor drug levels for efficacy and toxicitiy
ADE: Nephrotoxicity with elevated levels
Rare: ototoxicity – very high levels
Red Man’s Syndrome – histamine mediated reaction secondary to rapid infusions - not an allergic , simply slow the infusion time
Fifth generation cephalosporins
Ceftaroline (Teflaro) IV
Breaks the rule??
Spectrum : covers MRSA, does not cover Pseudomonas
“Ceftriaxone with MRSA coverage”
Approved for pneumonia and skin infections
Currently being studied for other serious infections (bone)
Monobactams
Aztreonam (Azactam) – IV
Inhibit cell wall synthesis
Only covers gram-negative organisms
Spectrum: very broad, including Pseudomonas aeruginosa
Safe to use in PCN allergy
Similar structure to ceftazidime , caution in patients allergic to ceftazidime
Not commonly used empirically due to its lack of gram-positive coverage, high cost
Well tolerated, similar ADE to cephalosporins
Beta-lactamase Inhibitors
Amoxicillin-clauvulanate (Augmentin)
Ampicillin-sulbactam (Unasyn)
Piperacillin-tazobactam (Zosyn)
inhibit the activity of the beta-lactamases
preserves the spectrum of the agent it’s combined with
Unasyn and Zosyn are IV, Augmentin PO
Used empirically for hospital infections
Augmentin = high rates of diarrhea
Very commonly used
Daptomycin (Cubicin) – IV
MOA: causes rapid depolarization leading to inhibition of protein, DNA and RNA synthesis
Spectrum: ONLY gram-postiive organisms including MSSA, MRSA, VRE
Clinical Uses: Alternative agent to linezolid for resistant gram-positive infections
NOT used to treat pneumonia (inactivated by lung surfactant)
ADE: associated with myopathy, monitor CPK
Dose largely dependent on MIC, do not assume sensitivity
Metronidazole (Flagyl) IV, PO
MOA : interferes with DNA synthesis
Spectrum: anaerobic gram-negative organisms, C. diff
First line recommendation for mild C. diff
Use in combo with vancomycin for severe C. diff
ADE: GI upset, metallic taste, headache, dark urine, peripheral neuropathy
Exhibits a disulfiram-like reaction, do not take with ETOH, will cause severe vomiting
Excellent bioavailability, IV and PO interchangeable
Used for distal colon infections
Cephalosoporins ADE
Overall well tolerated
Hypersensitivity less commonly seen
5-10% cross reactivity see in those allergic to PCNs
Clinically ok to challenge if patient experienced rash
Anaphylaxis, request allergy testing or avoid
GI intolerance (diarrhea)
Seizure in not dosed properly (Cefepime more common)
Neutropenia with long term use
Anti-Staphylococcal Penicillin
Oxacillin Nafcillin Created to tx PCN-resistant Staph aureus Methicillin d/c because toxic Spectrum: MSSA , drug of choice for serious MSSA infections Very short half-life, dosed every 4 hours Cleared by liver, no renal adjustments *other beta lactams renally adjusted Oral option (dicoloxacillin) rarely used
Natural Penicillin (Penicillin V, Penicillin G)
Spectrum: staph aureus (PCN-susceptible), streptococcus, syphilis
No gram-negative activity
Initiallly excellent for skin infections
RESISTANCE
Available in IV and IM as Peniciilin G ,
V is oral form (low absorption)
Total Exposure drugs
Azithromycin
Vancomycin
Polymyxin B / Colistin - IV
MOA: Alters charge of the cell membrane and leads to increased permeability of the membrane -> cell death
Spectrum: broadest antibiotic available to treat gram-negative organisms
Used as a last line resort for multi-drug resistant GNRs
MUST always be used in combo with other antibiotics to px resistance
ADE: nephrotoxicity , respiratory paralysis (rare)
Clindamycin (Cleocin) – IV , PO
MOA: Inhibits protein synthesis
Spectrum: Broad gram-positive (including MRSA) anaerobic pathogens (including oral pathogens) and minimal gram-negative (mainly anaerobic enteric gram-negative organism)
Used in patients with penicillin allergies for skin infections
ADE: GI upset (high rates of diarrhea)
First Generation Cephalosporins
Cephalexin (Keflex) –PO
Cefazolin (Ancef) – IV
Alternative to anti-staphylococcal penicillins
Spectrum: Streptococcus, Staph aureus (MSSA)
Minimal gram-negative activity – resistance
Short ½ life , dosed 3 – 4 x a days
Very common for skin infections and prophylaxis prior to surgeries
ALL ANTIBIOTICS
Development of C. diff overgrowth
Development of resistance
Will adapt to all that tries to kill them
Vanco Dosing
Dose based on total body weight Usually 15 mg/kg/dose with interval based on renal function: CrCl (ml/min) Interval >60 every 12 hrs 20-60 every 24 hrs <20 based on level
Concentration dependent drugs
Aminoglycosides
Fluoroquinolones
Daptomycin
PSEUDOMONAS DRUGS
Zero Preference for CLAMs and CARBs
Zosyn (Piperacillin/tazobactam), Polymyxins, Fortaz (Ceftazidime), Ciprofloxacin, Levofloxacin, Aztreonam, Maxipime, Aminoglycosides, CARBapenems (not ertapenem)
Tetracyclines
Doxycycline (Vibramycin) IV, PO
Minocycline (Minocin) IV, PO
Tigecycline (Tygacil) IV
MOA: inhibit protein synthesis
Spectrum: expanded gram-positive coverage (including MRSA) and gram-negative (NOT pseudomonas)
Tigecycline also has anaerobic activity and VRE
Extensive distribution (bone, skin)
ADE – all have extensive GI intolerances
Tigecycline – n/v in 40% of patients
Minocycline – higher vestibular toxicities (vertigo)
Do not use in pregnancy , kids < 8 y/o
Bone deformity and teeth staining
Photosensitivity (avoid sunlight)
Amino-penicillin
Amoxicillin , Ampicillin
Developed to provide gram-neg coverage
Spectrum: Streptococcus, Enteric gram-negative rods, Haemophilus influenza, Enteroccus faecalis
Less reliable for staph aureus
Ampicillin avialbe IV and PO
Mainly used in IV form (oral with poor biovailablity)
Amoxicillin used PO (better bioavailablity)
Clinical use: otitis media and acute pharyngitis
Not used empirically for hospital infections
Gram negatives are usually resistant
Inactivated by beta-lactamases
Cephalosporins
Inhibit cell wall synthesis
Many drugs in this class, divided into generations based on spectrum of activity
Greater gram positive coverage in first generation
Greater gram negative coverage in fifth generation
Anti-Pseudomonal Penicillin
Piperacillin
include coverage for Pseudomonas aeruginosa (Hospital-associated GNR)
Spectrum : same as aminopenicillins (+ pseudomonas)
Only IV, used in hospital for serious infections
Not used empirically due to resistance
Beta-lactamase
Enzyme that hydrolyzes the beta-lactam ring
Antibiotic becomes inactive
Natural or acquired from other organisms
Sulfamethoxazole-trimethoprim (Bactrim) – IV, PO
MOA: inhibits production of folic acid, an essential component to cell production
Spectrum: very broad, gram-negatives (NOT pseudomonas) and gram-positives (including MRSA)
Excellent bioavailability (IV and PO interchangeable)
Contraindicated in patients with sulfa allergies
Useful for variety of indications including pneumonia, skin infections, UTI, bone infections and more
ADE: skin rxns can be very severe, neutropenia, nephrotoxicity, hyperkalemia, bone marrow suppression
Must adjust in renal dysfunction !!
Carbapenems
Ertapenem (Invaz) IV, IM —– only IM
Meropenem (Merrem) IV
Imipenem/cilastatin (Primaxin) IV
Doripenem (Doribax) IV
Broadest beta-lactam class (also inhibit cell wall synthesis)
Used as last-line options in resistant infections
Spectrum: Streptococcus, MSSA, all GNR (including Pseudomonas) and anaerobic gram-negatives
Ertapenem does not cover Pseudomonas or Acinetobacter
Stable against many beta-lactamases
Primaxin has risk of causing seizures bc of cilastatin component
Used interchangeably depending on hospital formulary
Well tolerated
Time Dependent drugs
Beta-lactams
Linezolid
Time-dependent
Greater bactericidal activity as drug concentration remains above the MIC
Third generation Cephalosporins
Ceftazidime (Fortaz) IV
Ceftriaxone (Rocephin) IV
Cefpodoxime (Vantin) PO
Developed to further expand gram-negative spectrum
Spectrum: Streptococcus, MSSA less so, enteric GNR, Pseudomonas (Ceftazidime only)
Increased stability against beta-lactamases
Inactivated by Extended-spectrum beta-lactamases (ESBLs)
Ceftriaxone: longer ½ life, highly protein bound, once daily dosing
Hepatically eliminated, no renal adjustments
Commonly used in hospital and outpatient for various reasons (pneumonia, skin, blood, bone, CNS)
Fluoroquinolones
Ciprofloxacin (Cipro) IV, PO
Levofloxacin (Levaquin) IV, PO
Moxifloxacin (Avelox) IV, PO
MOA: inhibit protein synthesis causing cell death
Spectrum: broad coverage including gram-positive (not MRSA) and gram-negatives
Ciprofloxacin – poor Streptococcus coverage, not used for pneumonia
Only Ciprofloxacin and Levofloxacin cover Pseudomonas , not moxifloxacin
Excellent distribution, used for nearly all infection types
Excellent bioavailability, can switch from oral to IV in serious infections
Very commonly used -> resistance development
Levofloxacin and moxifloxacin dosed once daily
ADE: *QTc prolongation, *peripheral neuropathy, tendonitis, *C.diff
Macrolides
Azithromycin (Zithromax) IV, PO
Clarithromycin (Biaxin) – PO
MOA: inhibits protein synthesis
Spectrum: streptococcus, minimal gram-negatives
Respiratory pathogens that cause pneumonia and URIs
Including atypicals – Mycoplasma pneumoniae
Also used for chlamydia
Anti-inflammatory properties seen with azithromycin – used for COPD
Post-antibiotic effect- Zpak given for 5 days, works ~9-10 days
ADE: GI upset, QTc prolongation , take with food
***Clarithromycin rarely used due to drug interactions (inhibits CYP 450 enzymes) , increased GI intolerance and more frequent dosing
Vanco Serum Concentration Monitoring
Trough – serum concentration collected 30 minutes prior to the 4th dose
Correlates with efficacy and toxicity
Desired concentrations
In lung and CNS infections the recommended trough concentrations are 15-20 mcg/ml
10-15 mcg/ml for other infections
Aminoglycosides
Amikacin, Gentamicin, Tobramycin
MOA: inhibit protein synthesis
Spectrum: only gram negative organisms, including Pseudomonas aeruginosa, synergy for gram + infections
Amikacin – reserved for gentamicin and tobramycin resistant gram-neg organisms
Used in combination with other agents to prevent resistance from developing
MUST be adjusted for renal dysfunction, only use conventional dosing
MUST monitor levels
ADE: nephrotoxicity : risk factors: concomitant nephrotoxins, dehydration, duration
Ototoxicity
Penicillin ADE
Hypersensitivity rxns
10% of US population reports allergy
Rash most common
Almost all agents are renally eliminated / require adjustments
Except Oxacillin and Nafcillin are hepatically eliminated – Hepatotoxicity
Overall well tolerated
GI intolerance / diarrhea – most common with oral agents
MRSA DRUGS
VTZDCBT
Very Tall Zebras Drink Coffee Before Tests
Vancomycin, Teflaro(Ceftarolinee), Zyvox(Linezolid), Daptomycin, Clindamycin, Bactrim, Tetracyclines
Concentration-dependent
Greater bactericidal activity as drug concentration (Cmax) exceeds the MIC
BETA-LACTAMS
Penicillins
Cephalosporins
Monobactams
Carbapenems
Linezolid (Zyvox) – IV, PO
MOA: inhibits protein synthesis
Spectrum: Gram+ including MSSA, MRSA, VRE
Clincal Uses: reserved for tx of VRE or staph infections
Excellent bioavailability = IV and PO interchangeable
ADE : thrombocytopenia, drug interactions with SSRIs (may cause serotonin syndrome), diarrhea
