Antibiotics

Question 1

Drug Factors (2)

Answer 1

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”

Question 2

Patient factors (4)

Answer 2

age, hepatic/renal function, allergies, pregnancy, cost

Question 3

Signs and symptoms consistent with infection- other

6

Answer 3

• 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

Question 4

Signs and symptoms consistent with infection- WBC

Answer 4

• 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)

Question 5

Signs and symptoms consistent with infection- sepsis/ septic shock (6)

Answer 5

• Decreased BP
• Glucose intolerance
• Tachypnea
• Tachycardia
• DIC- decreased Plt count and increased prothrombin time
• Decreased urine output

Question 6

What are 5 possible sites of infection?

Answer 6

• 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

Question 7

Identification of infecting pathogen

Answer 7

• 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.

Question 8

2 Types of Atypical Bacteria

Answer 8

• Chlamydia

* Mycoplasma

Question 9

Infection

Answer 9

the isolated organisms are from the specimen and causing the infection

Question 10

Colonization

Answer 10

isolated organisms are from the specimen, but are NOT causing symptoms

Question 11

Contamination

Answer 11

isolated organisms came from the patient’s skin or the environment

Question 12

Cultures and Sensitivities

Answer 12

• 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

Question 13

Minimum inhibitory concentration (MIC) (Pathogen)

Answer 13

the lowest antimicrobial concentration that prevents visible growth of an organism

Question 14

Susceptible (Pathogen)

Answer 14

you can get enough drug into the patient to treat the infection (MIC < attainable serum levels)

Question 15

Intermediate (Pathogen)

Answer 15

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

Question 16

Resistant (Pathogen)

Answer 16

you cannot get enough drug into the patient to treat the infection (MIC > attainable serum levels)

Question 17

“Time dependent killers”

Answer 17

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)

Question 18

“Concentration dependent killers”

Answer 18

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)

Question 19

Synergy

Answer 19

Use of two antibiotics together provides synergistic effects
– Synergy can be determined using lab tests
– Used for enterococcus endocarditis or bacteremia,
sepsis, pseudomonal infections

Question 20

Post antibiotic effect (PAE)

Answer 20

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

Question 21

Other Drug Factors (6)

Answer 21

• 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

Question 22

2 Types of Antibiotic Resistance

Answer 22

– Intrinsic resistance
• Naturally occurring resistance (i.e drug cannot
penetrate the organisms cell wall)
– Acquired resistance
• A normally sensitive organism becomes resistant

Question 23

Mechanisms of acquired resistance (3)

Answer 23

• 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

Question 24

Intravenous Administration

Answer 24

• 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

Question 25

Advantages of Oral Administration (8)

Answer 25

• 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

Question 26

Beta- Lactams MOA

Answer 26

Mechanism of action

• Bind to pencillin binding proteins and inhibit cell wall synthesis causing cell death

Question 27

4 Types of Beta-Lactams

Answer 27

PCN
Cephalosporins
β-lactamase inhibitors
Aztreonam

Question 28

4 Types of PCN

Answer 28

Natural penicillins
Aminopenicillin
Penicillinase resistant penicillins
Extended spectrum penicillins

Question 29

Natural PCN common uses

Answer 29

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)

Question 30

Aminopenicillins
Ampicillin
Amoxicillin
Common Uses

Answer 30

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

Question 31

Penicillinase resistant penicillin
Dicloxacillin Nafcillin- IV Oxacillin- IV
Methacillin- pulled from market
Common Uses

Answer 31

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.

Question 32

Extended-Spectrum penicillins
Ticarcillin/clavulanate Piperacillin/tazobactam
Common Uses

Answer 32

Nosocomial pneumonia, intra-abdominal infections, gynecologic infections, skin and soft tissue infections

Streptococcus, Staphylococcus (MSSA)
Enterobacteriaceae, Bacteroids

Question 33

β- Lactamase inhibitors

Answer 33

Enhances the antimicrobial activity against certain beta- lactamase producing organisms, extending the antibiotics antimicrobial spectrum
e.g clavulanate, tazobactam, sulbactam

Question 34

Adverse reactions-Penicillins

Answer 34

• 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%)

Question 35

Penicillin allergy/desensitization

Answer 35

1-10% of the population reports a PCN allergy

• Of those 10-20% have a positive skin test

Question 36

Special considerations of PCN

Answer 36

• 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

Question 37

Antibiotic- OC interaction

Answer 37

• 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.