Antibiotics Flashcards
Drug Factors (2)
Clinical efficacy- does this antibiotic reach the area of infection? Some have poor penetration into CSF, urine, synovial fluid, and peritoneal fluid, etc.
Pharmacokinetic and pharmacodynamics-
determine dose and dosing interval – “Time dependent killers”
– “Concentration dependent killers”
Patient factors (4)
age, hepatic/renal function, allergies, pregnancy, cost
Signs and symptoms consistent with infection- other
6
• Bilateral infiltrates on chest x-ray
• Copious amounts of yellow- green secretions
from ET tube
• Erythema surrounding CVC
• Increased ESR- although not specific to infection
• Confusion
• WBCs found in urinalysis
Signs and symptoms consistent with infection- WBC
- Increased WBC- but can be increased in other situations (major surgery, myocardial infarction, leukemia, corticosteroids)
- WBC may be normal (UTI), or low (neutropenia)
- “left shift” presence of immature WBCs- indicates bone marrow response to infection- (does not occur with inflammatory conditions, leukemia, or corticosteroids)
Signs and symptoms consistent with infection- sepsis/ septic shock (6)
- Decreased BP
- Glucose intolerance
- Tachypnea
- Tachycardia
- DIC- decreased Plt count and increased prothrombin time
- Decreased urine output
What are 5 possible sites of infection?
- Pneumonia-chestx-ray,yellow-greensputum production, tachypnea
- Intra-abdominal- recent surgery, abdominal pain, absent bowel sounds
- Urinary tract- Abnormal urinalysis >50WBC/HPF
- CVC- erythema at insertion site
- Blood
Identification of infecting pathogen
- Obtain samples prior to starting antibiotic therapy to avoid false negatives
- Perform blood cultures in all acutely ill febrile patients
- For RG- culture sputum, urine, blood and any drainage from CVC site. Can also consider culture of catheter tip depending on how easy it is to remove the catheter.
2 Types of Atypical Bacteria
- Chlamydia
* Mycoplasma
Infection
the isolated organisms are from the specimen and causing the infection
Colonization
isolated organisms are from the specimen, but are NOT causing symptoms
Contamination
isolated organisms came from the patient’s skin or the environment
Cultures and Sensitivities
• Provides the final identification of the organism and information on the effectiveness of antimicrobials
• Results in about 24-48 hours
• Results are reported as S (sensitive) R
(resistant) or I (intermediate)
MIC= determines how resistant the bacteria is
Minimum inhibitory concentration (MIC) (Pathogen)
the lowest antimicrobial concentration that prevents visible growth of an organism
Susceptible (Pathogen)
you can get enough drug into the patient to treat the infection (MIC < attainable serum levels)
Intermediate (Pathogen)
you may not be able to get enough drug into the patient to treat the infection unless the drug is safe enough to give in high doses or the drug concentrates exceptionally well at the infection site (MIC
Resistant (Pathogen)
you cannot get enough drug into the patient to treat the infection (MIC > attainable serum levels)
“Time dependent killers”
killing is dependent on the time an organism is in contact with the drug. So, the duration that drug concentrations are above the MIC (T>MIC=time> minimum inhibitory concentration) is important (e.g beta-lactams, vancomycin)
“Concentration dependent killers”
killing is dependent on the concentration of the drug that the organism is exposed to – the higher the concentration the greater the killing (peak: MIC= peak serum drug concentration: minimum inhibitory concentration) (e.g fluoroquinolones, amino glycosides)
Synergy
Use of two antibiotics together provides synergistic effects
– Synergy can be determined using lab tests
– Used for enterococcus endocarditis or bacteremia,
sepsis, pseudomonal infections
Post antibiotic effect (PAE)
organism growth is suppressed for a period of time after the drug concentration falls below the MIC
– Aminoglycosides are concentration dependent killers with PAE and thus can be dosed once daily
Other Drug Factors (6)
- Antimicrobial spectrum of the antibiotic
- Available routes of administration
- Cost
- Drug interactions
- Evidence of efficacy with type of infection
- Safety in certain populations- renal failure, pregnancy
2 Types of Antibiotic Resistance
– Intrinsic resistance
• Naturally occurring resistance (i.e drug cannot
penetrate the organisms cell wall)
– Acquired resistance
• A normally sensitive organism becomes resistant
Mechanisms of acquired resistance (3)
• Detoxifying enzymes – can alter antibiotic structure and function
– Beta-lactamase- breaks down the beta-lactam ring of penicillin antibiotics
• Alteration in antibiotic target site
– e.g alteration of a penicillin binding protein
• Decreased cellular accumulation of antibiotic – Impaired influx (decreased permeability)
– Enhanced efflux
Intravenous Administration
- IV most often used for severe infections (endocarditis, meningitis, sepsis, osteomyelitis)
- Also used when patient cannot tolerate oral medications or when the patient has a non- functioning GI tract
- Many oral antibiotics have excellent bioavailability and should be given PO unless one of the above is present
Advantages of Oral Administration (8)
• Decreases cost- PO dosage form less expensive than PO
• PO dosing utilizes less resources- IV tubing, syringes, IV pumps, nursing time and pharmacy technician time
• Patients prefer PO as opposed to IV
• Reduced exposure of nosocomial pathogens through
the IV site
• Reduces the risk of phlebitis
• Increased patient mobility
• Potential for earlier discharge
• Decreases personnel time
Beta- Lactams MOA
Mechanism of action
• Bind to pencillin binding proteins and inhibit cell wall synthesis causing cell death
4 Types of Beta-Lactams
PCN
Cephalosporins
β-lactamase inhibitors
Aztreonam
4 Types of PCN
Natural penicillins
Aminopenicillin
Penicillinase resistant penicillins
Extended spectrum penicillins
Natural PCN common uses
Most commonly used for the treatment of pharyngitis, erysipelas, and syphilis (PCN G). >90% of Staphylococci produce penicillinase so PCN is not effective
(strep pyrogenes and Treponema Pallidum)
Aminopenicillins
Ampicillin
Amoxicillin
Common Uses
Amoxicillin used for the treatment of upper respiratory infections, H. pylori (in combo with clarithromycin and a PPI) Drug of choice for susceptible Enterococcal infections
Amox/ clavulanate used for skin infections, urinary tract infections, community-acquired pneumonia, lymphadenitis
Penicillinase resistant penicillin
Dicloxacillin Nafcillin- IV Oxacillin- IV
Methacillin- pulled from market
Common Uses
Drug of choice for β- lactamase producing staph Used in the treatment of cellulitis, mild to moderate
diabetic foot infections, septic arthritis, endocarditis
Staphylococcus spp., Streptococcus spp.
Extended-Spectrum penicillins
Ticarcillin/clavulanate Piperacillin/tazobactam
Common Uses
Nosocomial pneumonia, intra-abdominal infections, gynecologic infections, skin and soft tissue infections
Streptococcus, Staphylococcus (MSSA)
Enterobacteriaceae, Bacteroids
β- Lactamase inhibitors
Enhances the antimicrobial activity against certain beta- lactamase producing organisms, extending the antibiotics antimicrobial spectrum
e.g clavulanate, tazobactam, sulbactam
Adverse reactions-Penicillins
• Rash (maculopapular or urticarial)- most
common with ampicillin (9%, and in nearly all patients with mononucleosis)
• Anaphylaxis (0.05%), angioedema
• Interstitial nephritis (esp methicillin and
nafcillin)-usually reversible
• Positive Coombs test with hemolytic anemia (rare, only with high doses)
• Leukocytopenia/ thrombocytopenia
• C. difficile associated colitis
• Jarisch-Herxheimerreaction(withtreatmentof spirochetal infections ie. Treponema Pallidum, Lyme)
• Reaction due to release of large amts of toxins after bacterial killing- symptoms fever, chills, myalgia
• Ampicillin/ amoxicillin- GI upset/ diarrhea (esp amox/ clavulanate)
• Nafcillin/oxacillin-reversiblehepatitis(reportsof up to 10%)
Penicillin allergy/desensitization
1-10% of the population reports a PCN allergy
• Of those 10-20% have a positive skin test
Special considerations of PCN
- Monitoring:
- Renal function,hepatic function, CBC
- Food
- Administer on empty stomach-penicillin,ampicillin, dicloxacillin
- Administer with food-Moxatag®ER • Drug interactions
- Probenicid-probenicid decreases the renal tubular secretion of PCNs co-administration causes increased serum levels of antibiotics
- Methotrexate-PCNs inhibit the renal tubular secretion of mtx and may result in higher mtx levels
- Oral contraceptives
Antibiotic- OC interaction
• Proposed mechanism:
– Decreased enterohepatic circulation
– Increased liver degredation
– Displacement of the contraceptive steroid from its bioreceptor site
– Other considerations: women may not be feeling well or may be experiencing N/V which may lead to compliance issues with OC.
