NAPLEX Infectious Disease I Background Flashcards
(171 cards)
1
Q
e
The Presence of an Infection is Determined by:
A
-signs and symptoms: fever, elevated WBC count, and site specific symptoms (dysuria wiht UTIs)
-Diagnostic findings such as culture results, xrays, and markers of inflammation (eg. procalcitonin)
2
Q
Antibiotic selection is based on: (5 key components)
A
1.) Infection site and likely organisms at that site
2.) Infection severity and risk of multidrug resistant (MDR) pathogens (eg. CAP vs HAP)… infection that are hospital acquired often involve MDR organisms
3.) ABX characteristics (eg. spectrum of activity and ability to penetrate the site of infection)
4.) Patient characteristics including age, body weight, allergies, renal/ hepatic impairment, comorbidity, recent ABX use, colonization with resistant bacteria, immune function, pregnancy, etc.
5.) Treatment guidelines (IDSA, CDC)
3
Q
Common Bacterial Pathogens for Selected Sites of Infection
CNS/ Meningitis
A
- Streptococcus pneumoniae
- Neisseria Meningitidis
- Haemophilus influenzae
- Group B Streptococcus/ EColi (young)
- Listeria (young/old)
4
Q
Common Bacterial Pathogens for Selected Sites of Infection
Mouth
A
- Mouth flora (Peptostreptococcus)
- Anaerobic GNR (Prevotella)
- Viridan group streptococci
5
Q
Common Bacterial Pathogens for Selected Sites of Infection
Upper Respiratory (sinus and throat)
A
- Streptococcus pyogenes
- Streptococcus pneumoniae
- Haemophilus influenzae
- Moraxella catarrhalis
6
Q
Common Bacterial Pathogens for Selected Sites of Infection
Lower Respiratory (Community Acquired)
A
- Streptococcus pneumoniae
- Haemophilus influenzae
- Atypicals: Legionella, Mycoplasma, Chlamydophila
- Enteric gram neg rods (EColi, Klebsiella, Proteus) in alcohol use disorder
7
Q
Common Bacterial Pathogens for Selected Sites of Infection
Lower Respiratory (Hospital Acquired)
A
- Staphylococcus aueus (MRSA)
- Pseudomonas aeruginosa
- Acinetobacter baumannii
- Enteric gram neg rods (including ESBL+, MDR)
- Streptococcus pneumoniae
8
Q
Common Bacterial Pathogens for Selected Sites of Infection
Urinary Tract
A
- E. coli, Proteus, Klebsiella
- Staphylococcus saprophyticus
- Enterococci
9
Q
Common Bacterial Pathogens for Selected Sites of Infection
Bone/ Joint
A
- Staphylococcus aureus
- Staphylococcus epidermidis
- Streptococci
- Neisseria gonorrhoeae
- GNR (only in specific situations)
10
Q
Common Bacterial Pathogens for Selected Sites of Infection
Skin/ Soft Tissue
A
- Staphylococcus aureus
- Staphylococcus epidermidis
- Streptococcus pyogenes
- Pasteurella multocida
- +/- aerobic/anaerobic gram neg rods (in diabetics)
11
Q
Common Bacterial Pathogens for Selected Sites of Infection
Heart/ Endocarditis
A
- Staphylococcus aureus, including MRSA
- Staphylococcus epidermidis
- Streptococci
- Enterococci
12
Q
Common Bacterial Pathogens for Selected Sites of Infection
Intra-Abdominal
A
- Enteric GNR,
- Enterococci
- Streptococci
- Baeteroides species
13
Q
Define Empiric Treatment and the use of Antibiogram
A
Empiric treatment - often started when microbiology results are pending. This empiric treatment is usually a broad spectrum abx (covers several types of different organisms) and can be guided by antibiogram.
An antibiogram combines culture data from patients at a single institution into one chart, such that all gram positive or gram neg organisms cultured at a hospital pver a specific time period (usually 1 year). It shows susceptibility patterns and can be used to monitor resistance trends over time. Antibiogram is also used to select empiric treatment.
14
Q
Gram staining uses and limitations?
A
Cultures are taken from the infection site (e.g., lung
secretions, urine, blood, tissue from a wound or fluid from an abscess) and sent to the microbiology lab. The Gram stain categorizes the organism by shape (or morphology). The Gram stain provides quick, preliminary results (e.g.,Gram-negative rods), but does not identify the exact organism (e.g., Klebsiella pneumoniae). The Gram stain results provide a
clue about what organism may be causing the infection and an opportunity to adjust the empiric antibiotic regimen
15
Q
Gram Staining
Gram positive vs gram negative vs atypical: how do they show up on gram staining?
A
- Gram-positive organisms: have a thick cell wall and stain dark purple or bluish from the crystal violet stain.
- Gram-negative organisms: have a thin cell wall and take up the safranin counterstain, resulting in a pink or reddish color
- Atypical organisms: do not have a cell wall and do not stain well
16
Q
Gram-Positive
(appear dark purple): List morphology and name of the organisms
A
17
Q
Gram-Negative
(appear pink): List morphology and name of the organisms
A
18
Q
Atyplcals
(do not Gram stain well): List examples of Atypicals
A
19
Q
Describe the process of identifying organisms and what is done to determine which ABX are useful as treatment (MICs)
A
The microbiology lab uses various methods to determine which organism is present in the sample; for example, some Gram-negative bacteria (e.g., E. coli) break down lactose (a sugar) in a unique way and some do not (e.g., Pseudomonas).
Staphylococci (gram positive occuring in clusters) can be differentiated with a coagulase (enzyme) test. Staphylococcus aureus s colagulase-positive; other staphylococcus species (eg epidermidis) are sometimes referred to as coagulase-negative staphylococci (CoNS).
Once organism is identified, susceptibility testing is performed to determine which ABX are useful for treatment. The bacteria is grown on agar and exposed to varying concentration of select ABX.
The lab identifies the minimum concentration
of each antibiotic that inhibits bacterial growth, which is called the minimum inhibitory concentration (MIC). MICs. The lab compares the MIC to the susceptibility breakpoint, which is the usual drug concentration that inhibits bacterial growth [and is determined by the Clinical & Laboratory Standards Institute (CLSI). An interpretation is made as to which drugs inhibit
growth (and at what concentration) and which drugs do not.
20
Q
What is a culture and susceptibility report?
A
The culture and susceptibility ( C & S) report is usually available within 24- 72 hours. The C & S report identifies the organism and the results of the susceptibility testing. The empiric antibiotics can be streamlined to narrower spectrum treatment based on the C & S report. MICs are specific to each ABX and organism and should be compared amoung different ABX.
21
Q
Look over: culture and susceptibility report. What does S - susceptible, I - intermediate, and R - resistant means?
A
- Susceptible (S): drug are effective and should be selected
- Intermediate (I): may be effective under specific circumstances (eg. high dose, extended infusion), but usually would not be selected over a drug that is reported as susceptible.
- Resistant (R): drug is resistant to organism and should not be selected!
22
Q
The general steps on starting ABX and what to consider
A
- Empiric treatment: select empiric treatment based on the likely organisms at the at the infection site… also, is the patietn at risk for MRSA? MDR? provide coverage for that too. Use antibiogram and gram stain if avalible to guide tx choice.
- Streamline: When the C and S results are avalible, streamline to a more narrow spectrum antibiotics as soon as possible; if more than 1 organisms are presented… try to find abx that covers both! Consider IV:PO conversion if patient is clinically stable, eating, and if there is an appropriate PO option.
- Assess the patient : monitor for improvement of signs and symptoms. a lack of response can be multifactorial (ie. inadequate dose, nonadherance, uncontrolled sources, resistance, DDI). Determine the duration of treatment.. do not let abx continue unnecessarily.
23
Q
Antibiotic resistance: what is it? and what are the 4 most common mechanism of resistance?
A
Abx resistance is the ability of an organism to multiply in the presence of a drug that normally limits its growth or kills it.
1. Intrinsic resistance
2. Selection pressure
3. Acquired resistance
4. Enzyme inactivation
24
Q
Common mechanism of resistance?
Intrinsic Resistance
A
The resistance us NATURAL to the organism . For example, E.Coli is resistant to vancomycin b/c this antibiotic is too large to penetrate the bacterial cell wall of E.Coli!
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# Common mechanism of resistance?
Selection Pressure
Resistance occurs when abx kills off susceptible bacteria, leaving behind more resistant strains to multiply. For example, normal GI flora includes enterococcus. When abx (eg vancomycin) eliminates susceptible enterococci, vanco resistant enterococcus (VRE) can become predominant.
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# Common mechanism of resistance?
Acquired Resistance
Bacterial DNA containing resistant genes can be transferred between different species and/or picked up from dead bacterial fragments in the enviroment.
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# Common mechanism of resistance?
Enzyme Inactivation
Enzymes produced by bacteria breaks down the antibiotic rendering it useless!
- bacteria that produces **beta lactamases** break down beta lactams (eg penicillins) before they can bind to their site of activity. Beta Lactamase inhibitors (eg. Clavulanate, sulbactam, tazobactam, avibactam) are combined with some beta lactams to preserve or increase their spectrum of activities
- **Extended spectrum beta-lactamases** (ESBLs) are beta lactamases that can break down ALL penicillins and most cephalosporins. Organisms that produce ESBLs can be difficult to kill and serious infections involving these organisms are treated with **carbapenems or newer cephalosporins/ beta lactamase inhibitors** (ie. ceftazidime-avibactam IV; and ceftolozane-tazobactam PO)
- **Carbapenem-resistant enterobacterales **(CRE) are MDR gram negative organisms (eg. Klebsiella, Ecoli) that produce enzymes (eg. carbapenemase) capable of breakng down penicillins, most cephalosporins and carbapenems. CRE infections typically tx with combination of abx that include drugs such as **polymyxins**.. these drugs have high risk of toxicity.
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List of Common Resistant Pathogens
- Klebsiella pneumoniae (ESBL, CRE)
- Escherichia coli (ESBL, CRE)
- Acinetobacter baumannii
- Enterococcus faecalis, Enterococcus faecium (VRE)
- Staphylococcus aeruginosa
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C diff infection and how it occurs after the use of abx? Symptoms of C. diff?
When abx kills normal, healthy GI flora along with the targeted pathogens, it can result in an overgrowth of Clostridioides difficile, which can produce toxins that inflame the GI mucosa leading to C Diff infection!
Symptoms: mild (loose stools/ abdominal cramp) to severe (pseudomembranous colitis that requires colectomy). All abx have warning for risk of Cdiff but the highest risk is broad spec penicillins and cephalosporins, quinolones, carbapenems, and clindamycin!
30
Antibiotic MOAs: know the general MOA of each antibiotic/ where they work on the bacteria
1.) beta lactams: inhibit bacterial cell wall synthesis by binding to penicillin binding proteins. Thus preventing the final step of peptidoglycan synthesis in bacterial cell walls.
31
Hydrophilic agents/ ABX: examples and properties
Examples: beta lactam, aminoglycosides, vancomycin, daptomycin, polymyxins
Properties:
- small volume of distribution = less tissue penetration
- Mostly renally eliminated = drug accumulation and side effects (nephrotox, sz) can occur if dose is not renally adjusted
- low intracellular concentration = not active against atypical (intracellular) pathogens
- poor-mod bioavalability = IV:PO ration is NOT 1:1!
32
Lipophilic Agents agents/ ABX: examples and properties
Example: Quinlones, Macrolides, Rifampin, Linezolid, Tetracyclines
Properties:
- Large volume of distribution = better tissue penetration
- Mostly hepatically metabolized = potential for hepatox and DDI
- Achieve intracellular concentration = active against atypical pathogens
- Excellent bioavalibility = IV:PO ratio is often 1:1
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# Dose Optimization
Cmax:MIC; concentration -dependent killing: what does that mean/ abx examples
Drugs with concentration -dependent killing
(such as aminoglycosides, daptomycin, quinolones) can be dosed less frequently and in higher doses to maximize the concentration above the MIC.
- Goal: high peak (increase killing), low trough (decrease toxicity)
- Dosing strategies: larger dose, long interval
34
Time>MIC; time -dependent killing: what does this mean/ abx examples
Drugs with time -dependent killing (such as beta -lactams = penicillins, cephalosporins, carbapenems) can be dosed more frequently or administered for a longer duration to maximize the time above the MIC. Examples include extending the infusion time of beta -lactam antibiotics (e.g. from 30 minutes to 4 hours) or administering the drug as a continuous infusion.
- Goal: maintain drug level> MIc
- Dosing strategies: shorter dosing interval, extended or continous infusion
35
AUC:MIC; Exposure-Dependent: what does that mean/ abx example
Example: vancomycin, macrolides, tetracyclines, polymyxins
Goal: exposure over time
Dosing strategies: varies
36
# **PENICILLIN**
Natural Penicillins: **Penicillin V Potassium** - brand name, dosage form, dose, consideration
- Brand: PenVK+
- Dosage forms: tablet, suspension
- Dose: PO 125-500mg Q 6-12hrs on empty stomach
- Consideration: A first-line treatment for strep throat and mild nonpurulent skin infections (no abscess)
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# **PENICILLIN**
Natural Penicillins: **Penicillin G Aqueous ** brand name, dosage form, dose
- Brand: Pizerpen-G
- Dosage form: IV injection
- Dose: 2-4 million units Q4-6H
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# **PENICILLIN**
Natural Penicillins: **Penldllln G Benzathine**: brand name, dosage form, dose, consideration/ BBW
- Brand: Bicillin L-A
- Dosage form: IM
- Dose: 1.2-2.4 million units x 1 (varies)
- BBW: Penicillin G benzathine: **not for IV use**; can cause cardio-respiratory arrest and death!
- Consideration: Drug of choice for syphilis (2.4 million units IM x 1)
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# **PENICILLIN**
Aminopenicillins: **Amoxicillin** - brand, dosage form, dose, consideration
- Brand: Moxatag
- Dosage form: tab, cap, chewable, suspension
- Dose: PO: dosing varies with formulation; 24-hr
ER tablet is taken once daily
- Consideration: 1st line tx for acute otitis media (80-90 mg/kg/day). Drug of choice for infective endocarditis prophylaxis before ental procedures (2 grams PO x 1, 30-60 minutes before procedure). Used in H Pylori Treatment
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# **PENICILLIN**
Aminopenicillins: **Amoxlclllln/Clavulanate** - brand, dosage form, dose, consideration
- Brand: Augmentin
- Dosage form: tab, chewable, suspension
- Dose: PO: dosing varies with formulation; XR
tablet is taken Q12H with food
- Consideration: CI - history of cholestatic jaundice or
Injection hepatic dysfunction associated with previous use...Severe renal impairment (CrCI < 30 ml/min): DO NOT USE ER Amox of amox/clav or 875 mg strength of
amoxicillin/clavulanate... Amoxicillin/clavulanate: use a 14:1 ratio to decrease, diarrhea caused by the clavulanate component!!!.. First-line treatment for acute otitis media (90 mg/kg/day) and for sinus infections (if an antibiotic is indicated)
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# PENICILLIN
Aminopenicillins: **Ampicillin** - brand, dosage form, dose, consideration
- Brand: N/A
- Dosage form: Injection, cap, suspension
- Dose: PO: 250-500 mg Q6H on an empty
stomach 1 hr before or 2 hrs after meals
IV/IM: 1-2 grams Q4-6H
- Consideration: Ampicillin PO is rarely used due to poor bioavailability; amoxicillin is preferred if switching from IV ampicillin
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# PENICILLIN
Aminopenicillins: **Ampicillln/Sulbactam** - brand, dosage form, dose, consideration
- Brand: Unasyn
- Dosage form: Injection
- Dose: IV: 1.5-3 grams Q6H
- Consideration: Diluted in NS only!
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# **PENICILLIN **
Extended-Spectrum Penicillins: **Piperaclllln/Tazobactam** - brand, dosage form, dose, consideration
- Brand: Zosyn
- Dosage form: Injection
- Dose: IV: 3.375 grams Q6H or 4.5 grams Q6-8H
Prolonged or extended infusions: 3.375-4.5 grams IV Q8h(infused over 4 hours)
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# **PENICILLIN**
**Antistaphylococcal Penicillins**: list the 3 abx, dose, and consideration
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Penicillin Drug Class General Side Effects and Monitoring
1. SIDE EFFECTS
Seizures (with accumulation when not dose adjusted corrected in renal dysfunction), GI upset, diarrhea, rash (including SJS/TEN)/allergic reactions/anaphylaxis,
hemolytic anemia, renal failure, myelosuppression with prolonged use, increases LFTs
2. MONITORING
Renal function, symptoms of anaphylaxis with 1st dose, CBC and LFTs with prolonged courses
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Penicillin Drug Interaction
■ Probenecid can INCREASE the levels of beta-lactams by interfering with renal excretion. This combination is sometimes used intentionally in severe infections to INCREASE antibiotic levels.
■ Beta-lactams (except nafcillin and dicloxacillin) can
enhance the anticoagulant effect of warfarin by inhibiting the production of vitamin K-dependent clotting factors. Nafcillin and dicloxacillin (CYP inducer) can inhibit the anticoag effects of warfarin.
■ Penicillins can INCREASE the serum concentration of methotrexate
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# **CEPHALOSPORINS **
**Cefazolin**: gen? dosage form? dose?
- 1st Gen
- IV/IM
- 1-2 grams Q8h
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# **CEPHALOSPORINS **
**Cephalexin**: brand? gen? dosage form? dose?
- Keflex
- 1st gen
- oral
- 250-500mg Q6-Q12h
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# **CEPHALOSPORINS **
**Cefuroxime**: gen? dosage form? dose?
- 2nd gen
- PO,IV,IM
- 250-1500mg Q8-12h
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# **CEPHALOSPORINS **
**Cefotetan:** brand, gen, dosage form, dose, warnings
- Cefotan (brand d/c but name still use in practice)
- 2nd gen
- IV/IM
- 1-2 grams Q12h
- warning: contains a side chain (N-methylthiotetrazole) whihc can increase bleeding and cause disulfiram like rxn with alcohol ingestion
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# **CEPHALOSPORINS **
**Cefoxitin**: gen, dosage form, dose
- 2nd gen
- IM/IV
- 1-2 grams Q 6-8h
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# **CEPHALOSPORINS **
**Cefdinir**: gen, dosage form, dose
- 3rd gen
- Oral
- 300 mg Q12hr or 600mg QD
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# **CEPHALOSPORINS **
**Ceftriaxone:** gen, dosage form, dose, CI, notes
- 3rd gen
- IV/IM
- 1-2 grams Q12-24hrs
- contraindications: hyperbilirubinemic neonates (causes biliary sludging kernicterus), concurrent use of calcium containing IV products in neonates less than 28 days ... insoluble precipitates may form! so concurent admin should be avoided in all patients - but in adults it can be admin in same line but line needs to be flushed and admin at different tiem of day. HOWEVER. it's CI in neonates!
- notes: no renal adjustments!, CNS penetration at high doses when meninges inflammed
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# **CEPHALOSPORINS **
**Cefotaxime: **gen, dosage form, dose
- 3rd gen
- IV/IM
- 1-2 grams Q4-12hrs
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# **CEPHALOSPORINS **
**Ceftazidime**: brand, gen, dosage form, dose
- Fortaz (d/c), Tazicef
- 3rd gen group 2
- IV/IM
- 1-2 grams Q8-12hrs
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# **CEPHALOSPORINS **
**Cefepime**: gen, dosage form, dose
- 4th gen
- IV/IM
- 1-2 grams Q8-12h
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# **CEPHALOSPORINS **
**Ceftaroline fosamil**: brand, gen, dosage form, dose
- Teflaro
- 5th gen
- IV
- 600mg Q 12h
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# **CEPHALOSPORINS **
list the 2 cephalosporins combination meds, brands, dosage forms, and dose
1.) ceftazidime/ avibactam (Avycaz), IV: 2.5 grams Q 8hrs (active againt CRE!)
2.) Ceftolozane/tazobactam (Zerbaxa). IV: 1.5-3 grams Q8h
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# **CEPHALOSPORINS **
Cephalosporins: general warnings and side effects
Warnings:
- cross reactivity with PCN allergy (<10%, higher risk with 1st gen cephalosporins) DO NOT use in patients with a type 1 hypersensitivity to PCN (swelling, angioedema, anaphylaxis)
Side Effects:
- SZ (with accumulation when not correctly dose/ renal adjusted), GI upset, diarrhea, rash/allergic rnx, anaphalaxis, hemolytic anemia (identify with positive coombs test), myelosupp. with long term use, increased LFTs, fever, serious skin rnx (SJS/TEN) - PRETTY MUCH SIMILAR TO PNC
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# Key feat of cephalosporins
Outpatient (oral) options.. what are each of these commonly use to treat in an outpt setting?
1. 1st gen: cephalexin
2. 2nd gen: Cefuroxime
3. 3rd gen: Cefdinir
1. 1st gen: cephalexin - skin infection (MSSA), strep throat
2. 2nd gen: Cefuroxime - acute otitis media, CAP
3. 3rd gen: Cefdinir - acute otitis media
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# Key feat of cephalosporins
Inpatient (parenteral) options .. what are each of these commonly use to treat in an in patient setting? PART 1
1.) 1st gen: Cefazolin
2.) 2nd gen: Cefotetan and Cefoxitin
3.) 3rd gen: Ceftriaxone and Cefotaxime
1.) 1st gen: Cefazolin - surgical prophylaxis
2.) 2nd gen: Cefotetan and Cefoxitin - anaerobic coverage (B. fragilis), surgical prophylaxis
3.) 3rd gen: Ceftriaxone and Cefotaxime - CAP, meningitis, spontaneous bacterial peritonitis, pyelonephritis...note: ceftriaxone - no renal adj amd DO NOT use in neonates (0-28 days).
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# Key feat of cephalosporins
Inpatient (parenteral) options .. what are each of these commonly use to treat in an in patient setting? PART 2
1.) 3rd gen: Ceftazidime
2.) 4th gen: Cefepime
3.) Combination products: Avycar and Zerbaxa
4.) 5th gen: Ceftaroline
1.) 3rd gen: Ceftazidime - active against pseudomonas
2.) 4th gen: Cefepime - active against pseudeomonas
3.) Combination products: Avycar and Zerbaxa - used for MDR gram neg bugs (including pseudomonas)
4.) 5th gen: Ceftaroline - only beta lactam active agaisnt MRSA! commonly use: CAP, skin/soft tissue infections
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# **Carbapenem **
**Doripenem**: dosage form, dose, notes
Injection: IV: 500mg Q8hrs
NOTE: DO NOT use for tx for penumonia! (CAP or HAP)
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# **Carbapenem**
**Imipenem/Cilastain and Imipenem/Cilastatin/Relebactam**: brand name, dosage form, dose...why is imipenem a combination product?
1.) Imipenem/Cilastain (Primaxin IV) - IV: 250-1000mg Q6-8h
2.) Imipenem/Cilastatin/Relebactam (Recarbrio) - 1.25 grams Q6h
....NOTE: lmipenem is combined with cilastatin to prevent drug degradation by renal tubular
dehydropeptidase
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# **Carbapenem**
**Meropenem and Meropenem/Vaborbactam**: dosage form, dose
1.) Meropenem - IV: 500-1000mg Q8hr
2.) Meropenem/Vaborbactam (Vabomere) - IV: 4 grams Q8h (each dose infused over 3 hrs)
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# **Carbapenem**
**Ertapenem**: brand, dosage form, dose, note
- Brand: Invanz
- stable for normal saline NS only!
- IV/IM: 1 gram QD
- DOES NOT cover: PEA (pseudomonas, enterococcus, Acinetobacter)... commonly used for diabetes foot infection
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# **Carbapenem**
Carbapenem: Contraindication, warnings, side effects, monitoring, notes
- CI: anaphalaxis to beta lactam abx
- Warning: DO NOT use in patients with PNC allergy, CNS AEs (including sz, confusion)...risk increase with higher doses, renal impaired, or imipenem/cilastatin
- Side Effects: Diarrhea, rash/severe skin reaction (DRESS), bone marrow suppression with prolong use, increased LFTs
- Monitoring: Renal function, symptoms of anaphylaxis with 1st dose, CBC, LFTs
- NOTES: Carbapenems can decrease serum concentrations of valproic acid, leading to a loss of seizure control. Use with caution in patients at risk for seizures, or in combination with other drugs known to lower the seizure threshold (ie. clozapine, quinolones, bupropion, tramadol)
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# **Carbapenem**
Carbapenem: class effects, what do they NOT cover?, common uses?
- Class effect: all active against ESBL-producing bugs and (except Ertapenem) pseudomonas, do not use with PCN allergy, SZ risk
- What is NOT covered?: atypicals, VRE, MRSA, CDiff, Stentrophomonas. And Ertapenem does not cover PEA
- Common uses: polymicrobial infection (ie. Diabetes foot infection), empiric coverage when resistent is suspected, ESBL+ bugs
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# **MONOBACTAM**
**Aztreonam **
- MOA
- Coverage
- Dosage form
- Dose
- Side Effect
- Note
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**Aminoglycosides**: MOA, what does it cover?, how is it used, what are the 2 dosing strategies?
- **MOA**: Aminoglycosides bind to the ribosome, which interferes with bacterial protein synthesis and results in a defective bacterial cell membrane.
- **Coverage**: They primarily cover Gram-negative bacteria (including Pseudomonas);
- **How is it used **?: Aminoglycoside are typically used as a part of empiric tx with other abx (NOT used alone). Gentamicin and streptomycin are used for synergy, in combination with a beta-lactam or vancomycin, when treating Gram-positive infections (e.g. enterococcal endocarditis) . Streptomycin and Amikacin are used as second-line treatment for Mycobacterial infections.
Plazomicin, a newer drug in the class, is only indicated for complicated UTI and pyelonephritis when there are no alternative treatment options.
- **Dosing**: There are two dosing strategies for aminoglycosides; traditional dosing uses lower doses more frequently (e.g., Q8H if renal function is normal). Extended interval dosing uses higher doses (to attain higher peaks) less frequently (e.g., once daily if renal function is normal). With extended interval dosing there is less accumulation of drug.
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# Study tip gal
**Key Feat of Aminoglycosides**: Class effects, risks, and dosing strategies
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# **Aminoglycoside**
1.) Gentamicin
2.) Tobramycin
For each drug... List the dosage forms and the dosing (traditional vs. extended).
1.) Gentamicin: IV, IM, Ophthalmic, topical
2.) Tobramycin: IV, IM, Ophthalmic, Inhaled (for CF: Tobi)
.
Dosing for both is the same!
**Traditional IV Dosing: 1-2.5 mg/kg/dose** (lower dose for gram +, higher dose for gram -)
.
If patient is underweight: use TBW
If normal weight: IBW or TBW can be used
If obese: use ABW
.
**Renal Adjustment For Traditional Dosing**
- CrCl > 60: Q8h
- CrCl 40-60: Q12h
- CrCl 20-40: Q24h
- CrCl less than 20 : 1 dose, then dose per level
**Extended Interval IV Dosing**:** 4-7 mg/kg/dose** (freq is based on nonogram but shortest interval is Q 24h is renal is ok)
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# **Animoglycoside **
1. **Amikacin**: dosage form, dosing
2. **Plazomicin**: dosage form, dosing
1. Amikacin: IV/IM: 5-7.5 mg/kg/dose Q8h
2. Plazomicin: IV 15mg/kg Q24h (for complicated uti only! - MDR gram- UTI)
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**Aminoglycoside:** Boxed warning and general warning
1.) **Boxed warning**: Nephrotoxicity , ototoxicity, (hearing loss, vertigo, ataxia); avoid use with other neurotoxic/nephrotoxic drugs; neuromuscular blockade and respiratory paralysis; fetal harm if given in pregnancy
2.) **General Warning: ** Use caution in patients with impaired renal function, in the elderly, and those taking other nephrotoxic drugs (amphotericin B, cisplatin, polymyxins, cyclosporine, loop diuretics NSAIDs., radiocontrast dye, tacrolimus and vancomycin)
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**Aminoglycosides**: Monitoring
- General: Drug levels, renal function, urine output, hearing tests
- Traditional dosing: draw a trough level right before (or 30 minutes before) the 4th dose; draw a peak level 30 minutes after the end of the 30-minute drug infusion for the 4th dose
- Extended interval dosing: draw a random level per the timing on the nomogram
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**Aminoglycoside:TRADITIONAL DOSING:** TARGET DRUG CONCENTRATIONS: When peak and trough levels are drawn with the 4th aminoglycoside dose , the levels are compared to the goal peaks and troughs to determine if dose adjustments are needed... **what's the peak and trough goal of each animoglycoside? **
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Aminoglycoside: EXTENDED INTERVAL DOSING NOMOGRAM: **Hartford dosing**
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Quinolones: general, MOA, antibacterial activity, what does it cover?
Quinolones inhibit bacterial DNA topoisomerase IV and DNA gyrase (topoisomerase II) inside the bacteria. This prevents supercoiling of DNA and promotes breakage of doublestranded DNA. Quinolones have **concentration-dependent** antibacterial activity and a broad-spectrum of activity against a variety of Gram-negative, Gram-positive and atypical pathogens.
79
# Quinolones
**Levofloxacin**: brand, dosage forms, renal adj?, dose, general/ important info
- Brand: Levaquin
- tablet, solution, injection, ophthalmic
- PO/IV: 250-750mg QD
- CrCl less than 50: use Q48h and or decrease the dose!
- Levofloxacin is refered to as "respiratory quinolones" due to its enchanced coverage **of S. Pneumoniae and atypical pathogens **
- enhanced Gram negative activity, including coverage of Pseudomonas... are typically used in combination with another agent (e.g., a beta-lactam} when treating Pseudomonas infections empirically
80
# Quinolones
**Moxifloxacin**: brand, dosage forms, renal adj?, dose, general/ important info
- Brand: Avelox, Vigamox eye drops)
- Tablet, inj, ophthalmic
- IV/PO: 400mg Q24hrs
- Only quinolone that does not need renal adj! No renal dose adj required
- Moxifloxacin is refered to as "respiratory quinolones" due to its enchanced coverage **of S. Pneumoniae and atypical pathogens **
- Moxifloxacin has enhanced Gram-positive and anaerobic activity and can be used alone for polymicrobial infections (e.g., intra-abdominal infections) . Moxifloxacin is the only quinolone that cannot be used to treat UTI! (will not concentrate in urine)
81
# Quinolones
**Ciprofloxacin**: brand, dosage forms, combination with other drugs?, renal adj?, dose, general/ important info
- Brand: Cipro, Ciloxan (eye drops), Cetraxal (ear drops)
- tab, inj, suspension, ointment, otic, ophthalmic
- Combination ear drops: +dexamethasone (Ciprodex), +flucinolone (Otovel), +hydrocortisone (Cipro HC)
- PO: 250-750mg Q12H, IV: 200-400mg Q8-12h
- CrCl 30-50 do Q12h, CrCl less than 30 do Q18-24hr
- enhanced Gram negative activity, including coverage of Pseudomonas... are typically used in combination with another agent (e.g., a beta-lactam} when treating Pseudomonas infections empirically
- DO NOT USE WITH tizanidine.
82
# Quinolones
**Delafloxacin**: brand, dosage forms, combination with other drugs?, renal adj?, dose, general/ important info
- Brand: Baxdela
- Tablet, injection
- PO:450mg Q12h, IV: 300mg Q12h
- CrCL less than 15 not reccomended!!
- Delafloxacin is active against MRSA and is the preferred quinolone if treating skin infection suspected to be caused by MRSA. Other quinolones should be avoided due to high rate of MRSA resistance!
83
# Other Quinolones (for completion)
1.) Gatifloxacin
2.) Ofloxacin
List the brand names and anything important
1.) Gatifloxacin - Zymaxid eye drops. No oral !
2.) Ofloxacin (Ocuflox - eye drops). tablet, ophthalmic, otic. PO: 200-400mg Q12h, For CrCL under 30 dose adj required
84
**Quinolones**: BOXED WARNINGS
- **Tendon inflammation and/or rupture** (often in the Achilles tendon) within hours/ days of starting, or up to several months after completion of treatment: High risk with concurrent use of systemic steroids, in organ transplant patients and age> 60 years. D/C ASAP if symp occurs!
- **Peripheral neuropathy**: can last months to years after the drug has been discontinued and may become permanent. Discontinue immediately if symptoms occur
- **CNS effects** [seizures, tremor, restlessness, confusion, hallucinations, depression, suicidal thoughts, paranoia, nightmares, insomnia, increased ICP. Use with caution in patients with CNS disorders or with drugs that can cause SZ or lower the SZ threshold (ie. bupropion)
- Avoid in patients with **myasthenia gravis **(may exacerbate muscle weakness).
- Use last-line (only if no other possible treatments) for: acute bacterial sinusitis, acute exacerbation of chronic bronchitis and uncomplicated UTI (except moxifloxacin)
85
**Quinolones**: Warnings and Side Effects
- **QT Prolongation** (highest risk in Moxifloxacin > Levofloxacin > Ciprofloxacin); avoid in patient with known QT prolongation, or those who have additive risks (hypokalemia, use of other drugs that prolong QT interval (ie. antiarrthy drug: sotalol, amio, antipsy/ antidep: Haloperidol, citalopram, etc)
- **Hypo/Hyperglycemia**
- **Psy distrubances**: agitation, lack of attention, nervousness, delirium
- AVOID SYSTEMIC QUINOLONES IN KIDS AND PREG/ BREAST FEEDING DUE TO RISK OF **MUSCULOSKELETAL TOXICITY**
- **Aortic aneurysm and dissection**
- **photosensitivitiy, hepatox, crystalluria** (must stay hydrated)
SIDE EFFECTS: ** N/D, headache, seriouos skin reaction (SJS/ TEN)**
86
Quinolones Drug Interactions
1.) Antacids and other polyvalent cations (e.g., magnesium, aluminum, calcium, iron, zinc), multivitam ins, sucralfate, and bile acid resins can chelate and inhibit absorption.
2.) The phosphate binders Lanthanum carbonate (Fosrenol) and sevelamer (Renvela) can decrease the serum concentration of oral quinolones; separate
administration by at least 2 hours before, and at least 2 hours after (with lanthanum) or 6 hours after (with sevelamer).
3.) Quinolones can INCREASE the effects of warfarin, sulfonylureas, insulin and other hypoglycemic drugs.
4.) Caution with CVD, can DECREASE potassium and magnesium and with other QT-prolonging drugs (e.g., azole antifungals, antipsychotics, methadone, macrolides).
5.) Probenecid and NSAIDs can INCREASE quinolone levels.
6.) Ciprofloxacin is a P-glycoprotein substrate, a strong CYP1A2 inhibitor and a weak CYP3A4 inhibitor; ciprofloxacin can increase the levels of caffeine, theophylline and tizanadine by reducing metabolism.
87
**Macrolides**: MOA, general info, what does it cover?, what is it used for?
Macrolides bind to the 50S ribosomal subunit, resulting in inhibition of RNA-dependent protein synthesis. They have excellent coverage of atypicals (Legionella, Chlamydia, Mycoplasma and Mycobacterium avium complex) and Haemophilus. Macrolides are treatment options for community-acquired upper and lower respiratory tract infections and certain sexually transmitted infections (e.g., chlamydia, gonorrhea), but utility against S. pneumoniae, Haemophilus, Neisseria and Moraxella can be limited due to increasing resistance.
88
# Macrolides
**Azithromycin**: brands, dosage forms, dose, renal adj, other general info?
- Brand: Zithromax, ZPak
- tablet, suspension, inj, ophthalmic
- ZPak: 500mg day 1 then 250mg on day 2-5; TriPak: 500mg po for 3 days; Dosing vaires depending on issue; IV 250-500mg QD.
- No renal adj needed!
- Better gram - activity than erthromycin
89
# Macrolides
**Clarithromycin**:dosage forms, dose, renal adj, other general info?
- Tablet, ER Tablet, suspension
- PO: 250-500 mg Q12hrs or 1 gram ER QD
- CrCl less than 30? adj required
- Better gram + activity
90
# Macrolides
**Erythromycin**: brands, dosage forms, dose, renal adj, other general info?
- Brands: EES, Ery-tab, Erythrocin
- Capsule, tab, suspension, njection, topical, ophthalmic
- Dosing varies by product
- No renal adj need
91
**Macrolides**: Contraindications
- History of cholestatic jaundice/hepatic dysfunction with prior use
- **Clarithromycin and erythromycin**: do not use with lovastatin or simvastatin, pimozide, ergotamine or dihydroergotamine
- **Clarithromycin**: concurrent use with colchicine in patients with renal or hepatic impairment
92
**Macrolides**: Warnings, SEs
- **QT prolongation **(highest risk with erythromycin . azith > clarith); avoid in patients with known QT prolongation, or those with additive risks (hypokalemia, use of other drugs that prolong the QT interval, including Class la and Class Ill arrhythmias
- **Hepatotoxicity**; use caution in patients with liver disease
- Exacerbation of **myasthenia gravis **
- Clarithromycin: caution in patients with CAD (increase mortality has been documented...)
- Side Effects: GI upset, taste perversion, ototox, severe skin reaction (SJS, TEN, DRESS)
93
**Macrolides**: Drug interactions
- Erythromycin and clarithromycin are major substrates of CYP3A4 and are CYP3A4 inhibitors (moderate for erythromycin and strong for clarithromycin). Medications etabolized by CYP3A4 may need to be avoided (e.g., simvastatin and lovastatin: CONTRIANDICATED SO AVOID! ) and others may require close monitoring, or should be used with caution. Some examples include apixaban, colchicine, dabigatran, rivaroxaban, theophylline and warfarin.
- Azithromycin is a minor substrate of CYP3A4 and a weak inhibitor of CYP1A2 and P-gp; it has fewer clinically significant drug interactions.
- All macrolides: use caution with CVD, decreases potassium and magnesium and with other QT-prolonging drugs (e.g., azole antifungals, antipsychotics, methadone, quinolones) .
94
# Tetracycline
**Tetracyclines**: MOA, general information, what does it cover/ what is it used for?
- Tetracyclines inhibit bacterial protein synthesis by reversibly binding to the **30S ribosomal subunit**. They cover many Gram positive bacteria (Staphylococci, Streptococci, Enterococci, Nocardia, Bacillus, Propionibacterium spp.), Gram-negative bacteria, including respiratory flora (Haemophilus, Moraxella, atypicals) and other unique pathogens (e.g., spirochetes, Rickettsiae, Bacillus anthracis, Treponema pallidum).
- **Doxycycline** has broader indications, including respiratory tract infections (e.g., CAP), tick-borne/rickettsial diseases, spirochetes and sexually transmitted infections (chlamydia and gonorrhea). Doxycycline is an option for the treatment of
mild skin infections, caused by CA-MRSA, and VRE urinary tract infections. **Minocycline** is often preferred for skin infections, including acne.
95
# Tetracyclines
**Doxycycline**: brand, dosage form, dosing, renal adj, consideration?
- Brand: Vibramycin, Doryx, Oracea, etc.
- Capsule, tablet, suspension, syrup, inj
- PO/IV: 100-200mg QD in 1-2 divided dose
- No renal adj
- Take with food to decrease GI irritation
96
# Tetracyclines
**Minocycline**: brand, dosage form, dosing
- Minocin, Solodyn
- Capsule, tablet, injection
- PO/IV: 200 mg x 1 then 50-100 mg Q12h
97
Other Tertacyclines that are not too important
1. Eravacycline (Xerava) - injection 1mg/kg q12hr
2. Omadacycline (Nuzyra) - tablet/ inj - dose varies
3. Sarecycline (Seysara) - tablet, dosing varies
4. Tertacycline capsule - PO: 250-500 mg q6hr on empty stomach. need dose adj if CrCl is less than 50
98
Tetracycline: Warnings, Side Effects, Monitoring
**Warning: **
- Children < 8 years of age, pregnancy and breastfeeding (suppresses bone growth and skeletal development, permanently discolors teeth)
- Photosensitivity, tissue hyperpigmentation, severe skin reactions (DRESS/SJS/TEN), exfoliative dermatitis
- Gastrointestinal inflammation/ulceration
- Minocycline: drug-induced lupus erythematosus (DILE)
**Side Effects:** N/V/D, rash
**MONITORING:** LFTs, renal function, CBC
99
Tetracycline Drug Interactions
- Antacids and other polyvalent cations (e.g., magnesium, aluminum , calcium, iron, zinc), multivitamins, sucralfate, bismuth subsalicylate and bile acid resins can chelate and **inhibit tetracycline absorption**. Separate doses (1 - 2
hours before or 4 hours after the chealting drugs) . Dairy products should be avoided 1 hour before or two hours after tetracycline.
- Lanthanum carbonate (Fosrenol) can DECREASE the concentration of tetracycline derivatives; must seperate by 2 hours
100
Key features of tetracyclines/ and it common uses
- **Doxy and Mino**: CA-MRSA skin infection, acne
- **Doxy**: first line for tickborne illnessess (Lyme disease, rocky mountain spotted fever), chlamydia, CAP, COPD exacerbation, bacterial sinusitis, VRE UTI
- **Tetra**: H.Pylori regimen
**DO NOT USE IN PREG, BREASTFEEDING, OR CHILDREN UNDER 8 Y/O**
101
**Sulfonamides**: General MOA, what does it cover/ used for?
**Sulfamethoxazole (SMX)** inhibits dihydrofolic acid formation from para-aminobenzoic acid, which interferes with bacterial folic acid synthesis. **Trimethoprim (TMP)** inhibits dihydrofolic acid reduction to tetrahydrofolate, resulting in inhibition of
the folic acid pathway. Sulfamethoxazole/trimethoprim (BACTRIM) covers Staphylococci (including MRSA and CA-MRSA); S. pneumoniae and Group A Strep coverage is unreliable. Activity against Gram-negative bacteria is broad, and includes Haemophilus, Proteus, E. coli, Klebsiella, Enterobacter, Shigella, Salmonella and Stenotrophomonas. Coverage includes some opportunistic pathogens (Nocardia, Pneumocystis, Toxoplasmosis), but Pseudomonas, Enterococci 1 atypicals and anaerobes are not covered.
102
# Sulfonamides
Sulfamethoxazole/
Trimethoprim (Bactrim, Bactrim DS): List all the different strenghts: SS vs. DS, the Sulfa/Trim ration, and dosage forms it comes it
- SS: 400mg SMX/ 80 TMP
- DS: 800mg SMX/ 160 TMP
- Tablets, suspensions, injection
- All products are formulated with SMX:TMP ratio of 5:1
103
**Sulfamethoxazole/Trimethoprim dosing for various disease states:**
1. Severe infection
2. Uncomplicated UTI
3. Pneumocystis Pneumonia PCP/PJP Prophylaxis
4. PCP/ PJP Treatment
1. Severe infection - PO/IV 10-20mg TMP/kg/day divided @6-8hrs (2 DS tablets BID or TID)
2. Uncomplicated UTI - 1 DS tablet PO BID x 3 days
3. Pneumocystis Pneumonia PCP/PJP Prophylaxis - 1 DS or SS tab QD
4. PCP/ PJP Treatment - IV/PO: 15-20mg TMP/kg/day divided Q6 (CrCl 15-30 no dose adj, less than 15? not reccomended)
104
**Sulfamethoxazole/Trimethoprim**: Contraindications and warnings
- **CI**: Sulfa allergies, anemia due to folate def, renal/hep disease, infant less than 2 months old
- **Warning: **Blood dyscrasias, including agranulocytosis and aplastic anemia; Skin reactions: SJS/TEN, thrombotic lhrombocytopenic purpura ITTP); Hemolytic anemia: can be immune- mediated (identified with positive Coombs test) or caused by G6PD deficiency..do not use with known deficiency and discontinue drug if hemolysis occurs; Hypoglycemia , thrombocytopenia; pregnancy (only use if benefit outweights risks - it blocks folic acid metabolism leading to congenital defects)
105
**Sulfamethoxazole/Trimethoprim**: Side effects, monitoring
- **Side effects: **Photosensitivity, increase K+, crystalluria (must take with 8oz h2o), N/V/D, anorexia, skin rash, decrease folate, false elevation of SCr, renal failure
- **Monitoring:** Renal function, electrolytes, CBC, folate
106
Sulfamethoxazole/Trimethoprim: Drug interaction
- SMX/TMP is a moderate-strong inhibitor of CYP2C8 and** CYP2C9** and can cause **significantly increase INR**. Caution should be used in combination with warfarin
- SMX/TMP can enchance the toxic effects of methotrexate. Effects of SMX/TMP can be decreased by the use of leucovorin or levoleucovorin.
- The risk for **hyperkalemia** will Increase if used in combination with ACE inhibitors, ARBs, aliskiren, aldosterone receptor antagonists (ARAs), potassium-sparing diuretics, NSAIDs, cyclosporine, tacrolimus, drospirenone-containing oral contraceptives or canagliflozin.
107
What are some ABX that are used for Gram +?
- Vancomycin
- Lipoglycopeptides
- Daptomycin
- Oxazolidinones
- Quinupristin/ Dalfopristin
108
# ABX for gram + infection
**Vancomycin**: general MOA, and what does it cover/ what is it used for?
Vancomycin is a glycopeptide that inhibits bacterial cell wall synthesis by binding to the D-alanyl-D-alanine cell wall precursor and blocking peptidoglycan polymerization. Vancomycin only covers Gram positive bacteria, including Staphylococci (MRSA),
Streptococci, Enterococci (not VRE) and C. difficile (PO route only).
109
# ABX for Gram + Infections
**Vancomycin**: Brand, dosage form, dosing, dosing (IV and PO), renal adj, consideration?
- Brand: Vancocin, Firvanq oral solution
- Capsule, oral solution, Injection
- Systemic infections (USE IV ONLY): 15-20mg/kg q 8-12hrs (use TBW). CrCl 20-40 use Q24h, CrCL less than 20 give one dose then dose per levels. Peripheral IV should not exceed mg/ml
- For C.Diff infection (Oral only): PO 125mg QID x 10 days.. 500mg QID is severe (in combo with IV metronidazole) NO RENAL ADJ FOR ORAL
- Note: First line for mod/severe MRSA infections!, consider alt drug when MRSA MIC > 2
110
# ABX for Gram + Infections
**Vancomycin: ** Warnings and Side Effects
**Warnings:**
- Ototoxicity and nephrotoxicity; caution with use of other nephrotoxic/ ototoxic drugs or with prolonged high serum concentrations (dose adjustment required in renal impairment)
- PO only for C.Diff (not systemic infection!) IV DOES NOT treat CDiff
- Vancomycin infusion reaction (aka RedMan syndrome) - NOT a true allergic rxn! (maculopapular rash, hypotension, flushing and chills from too rapid of an infusion rate - do not Infuse faster than 1 gram per hour) - slow down infusion rate
.
**Side Effects: **
- Abdominal pain, nausea (oral route), phlebitis (irritation to vein), myelosuppression (neutropenia/thrombocytopenia), drug fever, severe skin reactions (SJS/TEN)
111
112
# ABX for Gram + Infections
**Vancomycin:** Monitoring and trough level goals?
- Renal function, drug levels (see below), WBC
- AUC/MIC ratio (improved outcomes and less toxicity) or steady state trough (drawn 30 mins before 4th and 5th dose)
- **Serious MRSA infections** (eg. sepsis, bacteremia, endocarditis, meningitis, osteomyelitis, pneumonia): **AUC/MIC ratio of 400-600 reccomended or goal trough 15-20mcg/ml**
- **Other infections** (eg. UTI, skin infections): goal trough **10-15mcg/ml**
113
# ABX for Gram + Infections
**Vancomycin**: Drug Interactions
- The risk of **nephrotoxicity** is INCREASED when used with other nephrotoxic drugs (e.g., aminoglycosides, amphotericin B, cisplatin, polymyxins, cyclosporine, tacrolimus, loop diuretics, NSAIDs and radiographic contrast dye)
- Vancomycin can INCREASE the risk of **ototoxicity** when used with other ototoxic drugs (e.g., aminoglycosides, cisplatin, loop diuretics).
114
# ABX for Gram + Infections
**Lipoglycopeptides:** General MOA, what do they cover/ what are they used for?
Lipoglycopeptides (with the generic name suffix "-**vancin**") **inhibit bacterial cell wall synthesis** by 1) binding to the D-alanylD-alanine portion of the cell wall, blocking polymerization and cross-linking of peptidoglycan, and 2) disrupting bacterial membrane potential and changing cell permeability (due to the presence of a lipophilic side chain). They have **concentration-dependent** activity and have similar coverage to vancomycin (** with the exception that they only come in IV form and cannot be used to treat C. difficile infections**).
- Lipoglycopeptides only come in IV form! and all can cause infusion reaction (similar to vanco) with rapid administration...so slow down rate
115
# ABX for Gram + Infections
**Lipoglycopeptides:** Telavancin (Vibativ) - What is it approved for? Dosing?, BOXED WARNING, CI, Side Effects/Warnings, DDI
- Injection ; Approved for complicated skin and soft-tissue infections (SSTI) and hospital-acquired and
ventilator-associated pneumonia
- IV: 10 mg/kg daily; Infuse over 60 minutes to
prevent infusion reaction
- **BOXED WARNING**: Fetal risk - obtain pregnancy test prior to starting therapy; nephrotoxicity; increased mortality with pre-existing moderate-to-severe renal impairment (CrCI less than 50 ml/min)
- **Contraindication:** Concurrent use of IV unfractionated heparin (UFH)
- **Side Effects/ Warning**: QT Prolongation, Can cause falsely increase PT/INR/PTT but do not increase bleed risk
- **DDI: ** Avoid in patients w/ congenital long QT syndrome (QT prolongation or decomp HF). Use with caution with other meds that can cause prolong QT
116
# ABX for Gram + Infections
**Lipoglycopeptides:** Oritavancin (Orbactiv) - What is it approved for? Dosing?, Contraindication, Side Effects/Warnings
- Approved for SSTI
- Single-dose IV regimen: 1,200mg; Infuse over 3 hours
- **CI**: use of IV UFH for 120 hours (5 days) after oritavancin administration due to interference (false elevations) with aPTT laboratory results
- **Side Effects/ Warnings:** Can cause falsely increase PT/INR/PTT but do not increase bleed risk; use a different antibiotic if osteomyelitis is confirmed or suspected
117
# ABX for Gram + Infections
**Lipoglycopeptides:** Dalbavancin (Dalvance) - What is it approved for? Dosing?, Warnings
- Approved for SSTI
- Single-dose IV regimen: 1500 mg; Two-dose IV regimen: 1,000 mg x 1, then 500 mg one week later
- Infuse over 30 minutes; CrCI < 30 ml/min (not on dialysis): dose adjustment required
- Warnings: Increase ALT > 3x the upper limit of normal
118
# ABX for Gram + Infections
**Daptomycin**: general MOA, what does it cover/ what is it used for?
- **MOA:** Daptomycin is a cyclic lipopeptide. It binds to cell membrane components, causing rapid depolarization; this inhibits all intracellular replication processes, including protein synthesis, and causes cell death.
- **Activity**: Daptomycin has concentration- dependent antibacterial activity against most Gram-positive bacteria, including Staphylococci (MRSA) and enterococci (VRE). It has no activity against gram negative!
- Approved for complicated skin and soft-tissue infections (SSTI) and S. aureus (MRSA) bloodstream
infections, including right-sided endocarditis. **Do not use to treat pneumonia; drug is inactivated in the lungs by surfactant**
- only avalible in injection form
119
# ABX for Gram + Infections
**Daptomycin**: Brand names, dosing for different disease states (SSTI, Bacteremia/ Right Side endocarditis)
-** Brand:** Cubicin, Cubicin R
- **SSTI**: 4 mg/kg IV daily
- **Bacteremia/right sided endocarditis:** 6 mg/kg IV daily (up to 10mg/kg qd)
- CrCI < 30 :dose adjustment required
120
# ABX for Gram + Infections
**Daptomycin: **Warnings, Side Effects, Monitoring, Notes
- **Warnings:** **Myopathy and rhabdomyolysis** - discontinue in patients with s/sx and CPK > 1,000 units/L, or in asymptomatic patients with a CPK 2,000 units/L; consider temporarily withholding other drugs that can cause muscle damage (e.g., statins -DDI!) during treatment; Can falsely increase PT/INR, but does not increase bleeding risk; Peripheral neuropathy; Eosinophilic pneumonia - generally develops 2-4 weeks after treatment initiation.
- **Side Effects:** increase CPK, abdominal pain, pruritus, chest pain, edema, hypertension, acute kidney injury
- **Monitoring:** CPK level weekly (more frequently if on a statin or with renal impairment); muscle pain/
weakness, s/sx of neuropathy , dyspnea
- **Note**: Compatible wiht NS but no dextrose!
121
# ABX for Gram + Infections
**Oxazolidinones:** general MOA, what does it cover/ what is it used for?
Oxazolidnones: including Linezolid and tedizolid bind to the 50S subunit of the bacterial ribosome, inhibiting translation and protein synthesis . They
have coverage similar to vancomycin (e.g., MRSA), but also cover VRE!
122
# ABX for Gram + Infections
**Oxazolidinones:** Linezolid - Brand, dosage forms
- Brand: Zyvox
- Tablet, suspension, injection
- PO/IV: 600mg q12hrs; no renal adj needed. IV:PO ration is 1:1
123
# ABX for Gram + Infections
**Oxazolidinones:** Linezolid - Contraindications, Warnings, Side effects, Monitoring, Note/ consideration
- **CONTRAINDICATIONS**: Do not use with or within 2 weeks of MAO inhibitors
- **WARNINGS**: Duration-related myelosuppression (thrombocytopenia, anemia, leukopenia) when used > 14 days; peripheral and optic neuropathy when used> 28 days; serotonin syndrome; hypoglycemia - caution with insulin or other hypoglycemic drugs; seizures; lactic acidosis; increase BP; hyperthyroidism
- **Side Effects**: Decrease platelets/Hgb/WBC, headache, N/D, increase LFTs
- **MONITORING**: HR, BP, BG (in diabetes), weekly CBC, visual function
- **NOTES**: Do not shake linezolid suspension
124
# ABX for Gram + Infections
**Oxazolidinones:** Tedizolid - Brand, dosage forms, what it's approved for, warnings, side effects
- Tedizolid (Sivextro)
- Tablet. injection
- Approved for SSTI
- PO/IV: 200 mg daily for 6 days; No dose adjustment in renal impairment; IV:PO ratio is 1:1
- **Warnings**: Consider alternative treatment in patients with neutropenia
- **Side Effects**: N/D, paresthesias, hypertension, visual impairment, blurred vision **(Less GI side effects and myelosuppression compared to linezolid)**
125
# ABX for Gram + Infections
**Oxazolidinones:** Linezolid and Tedizolid Drug Interaction
Llnezolid and tedizolid are reversible monoamine
oxidase inhibitors. Avoid tyramine-containing foods and serotonergic drugs. Linezolid can exacerbate hypoglycemic episodes!
126
# ABX for Gram + Infections
**QUINUPRISTIN/DALFOPRISTIN**: General MOA, what is it used for?
This drug is a streptogramin; it binds to the 50S ribosomal subunit inhibiting protein synthesis. Quinupristin/dalfopristin covers most Gram-positive bacteria, including Staphylococci (MRSA) and Enterococcus (VRE caused by E.faecium but NOT E. faecalis). It is approved for complicated skin and soft-tissue infections, but is not well-tolerated; **use is typically limited to vancomycin resistant E. faecium infections. **
127
# ABX for Gram + Infections
**QUINUPRISTIN/DALFOPRISTIN**: Brand, dosing, side effects, notes
- Quinupristin/ Dalfopristin (Synercid)
- Injection: 7.5mg/kg q8-12hrs (infused over 60 mins); no renal adj
- **Side Effects: **Arthralgias/myalgias, infusion reactions = including edema and pain at Infusion site, phlebitis, hyperbilirubinemia, CPK elevations, GI upset, increased LFTs
- **Notes: ** Dilute in D5W only, admin via centeral line only
128
# ABX for Gram + Infections
**Tigecycline:** General MOA, what is it used for?
Tigecycline is a glycylcycline. It binds to the 30S ribosomal subunit inhibiting protein synthesis; structurally, it is related to the tetracyclines. Tigecycline has a broad spectrum of activity against Gram-positive bacteria, including Staphylococci
(MRSA) and Enterococci (VRE), Gram-negative bacteria, anaerobes and atypical organisms. Among the Gram-negatives, it has **no activity** against the "3 P's": Pseudomonas, Proteus, Providencia species. Tigecycline is approved for complicated skin and soft-tissue infections, intra-abdominal infections and community-acquired pneumonia; use is limited (**Due to increase in death - see Boxed Warning**).
129
# ABX for Gram + Infections
**Tigecycline:** Brand, where is it derived from, dosing, dose adj?
- Brand: Tygacil
- Derived from minocycline
- IV only: 100mg x 1 dose, then 50 mg q12h; dose adj for severe hepatic impaired only
130
# ABX for Gram + Infections
**Tigecycline:** Boxed warning, general warning, side effects, note/ consideration
- **Boxed warning:** Increase risk of death, use only when alternative treatments are not suitable !
-** General warnings**: Hepatotoxicity, pancreatitis, photosensitivity, teeth discoloration in children< 8 years old (avoid use)
- **Side Effects:** N/V/D , headache, dizziness, increase LFTs, rash/severe skin reactions (SJS)
- **Note**: Do not use for bloodstream infections; Reconstituted solution should be yellow-orange; discard if not this color
131
# ABX for Gram + Infections
**Polymyxin:** General MOA, what drugs are in this class?, what is it used for?
The polymyxin class consists of two drugs: **colistimethate** (sometimes referred to as colistin) and **polymyxin B**.
- **Colistimethate** is an inactive prodrug that is hydrolyzed to colistin. Colistin acts as a cationic detergent and damages the bacterial cytoplasmic
membrane, causing leakage of intracellular substances and cell death.
- Polymyxins cover Gram-negative bacteria, such as Enterobacter spp., E.coli, Klebsiella pneumoniae and Pseudomonas aeruginosa (but not Proteus spp.). Due to the risk of toxicities, **they are used primarily for MDR Gram-negative pathogens** in combination with other antibiotics.
132
# ABX for Gram + Infections
**Polymyxin:** Colistimethate - brand, dosage forms, doses, warnings, note/ consideration
- Brand: Coly-Mycin M
- Injection (can be used for inhalation
administration)
- IM/IV 2.5-5mg/kg/qd in 2-4 divided doses
- **Warnings**: Dose-dependent **nephrotoxicity** (monitor renal function and electrolytes). **Neurotoxicity**.
- **Notes/ Consideration: ** Avoid use with other nephrotoxic medications; Neurotoxicity can result in respiratory paralysis from neuromuscular blockade
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# ABX for Gram + Infections
**Polymyxin:** Polymyxin B - dosage forms, doses, boxed warnings, monitoring, note/ consideration
- Injection; IV: 15,000-25,000 units/kg/day divided q12h
- **Boxed Warnings**: Nephrotoxicity (dose-dependent); Neurotoxicity (dizziness, tingling , numbness, paresthesia, vertigo). Should only be administered to hospitalized patients; Avoid concurrent use of other neurotoxic or nephrotoxic drugs. Neurotoxicity can result in respiratory paralysis from neuromuscular blockade
- **Monitoring: **Renal function
-** Note:** 1mg = 10,000 units
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# Misc ABX
**Clindamycin:** general MOA, what does it cover?
Clindamycin is a lincosamide which reversibly binds to the 50S subunit of the bacterial ribosome inhibiting protein synthesis. It covers most gram positive bacteria including CA-MRSA and anaerobes. Does not cover Enterococcus or Gram negative pathogens and has limited to no gram negative anaerobic activities.
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# MISC ABX
**Clindamycin** - Brand, dosage form, dosing, boxed warning, general warning, side effects, note/consideration
- **Brand**: Cleocin, topical product brand names: Cleocin-T, Clindagel, and more
- Injection, capsule, topical, suspension
- PO: 150-450mg q6h; IV: 600-900mg q8h; no renal adj
- **Boxed warning**: C. Diff
- **General Warning**: Severe or fatal skin reactions (SJS/TEN/DRESS)
- **Side Effects**: N/V/D, rash, urticaria, increased LFT
- **Notes**: Perform a D-test on clindamycin-susceptible but erythromycin-resistant S. aureus. A positive D*test (flattened zone) indicates inducible clindamycin resistance, so avoid clindamycin use. It's commonly used for skin infections and as a dental abscess alternative to beta-lactam antibiotics.
136
# MISC ABX
**Metronidazole and Related Drugs**: General MOA, what they cover/ what are they used for?
- These antibiotics cause a loss of helical DNA structure and strand breakage resulting in inhibition of protein synthesis.
- Metronidazole has activity against anaerobes and protozoal infections. It is effective for bacterial vaginosis, trichomoniasis, giardiasis, amebiasis, C. diff (tho not preferred) and is used in combination regimens for intra-abdominal infections.
- Tinidazole is structurally related to metronidazole, but activity is limited to protozoa (giardiasis, amebiasis), trichomoniasis and bacterial vaginosis organisms.
- Secnidazole, a newer drug in the class, is only indicated for bacterial vaginosis
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**Metronidazole**: brand, dosage form, dose
- Brand: Flagyl
- tablet, capsule, injection, topical
- PO/IV: 500-750mg Q8-12hrs or 250-500mg Q6-8hrs; no renal adjustments, take IR with food to decrease GI upset; PO:IV ratio is 1:1
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**1. Tinidazole
2. Secnidazole**
List the dosage form, dose, considerations
1. Tinidazole - tablet: 2g po QD; take with food to minimize GI issues; no renal adj
2. Secnidazole (Solosec) - granule packet; PO 2 grams single dose (SEs of this drug: vulvovaginal candidiasis!!)
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**Metronidazole + related drugs**: Boxed warnings, contraindication, warnings, side effects
- Boxed warning: possibly carcinogenic based on animal studies
- Contraindication: Preg (1st trimester), use of alcohol or propylene glycol-containing products during treatment within 3 days of treatment d/c (disulfiram rxn); Metronidizole: use of disulfiram within the past 2 wks; Tinidazole: breastfeeding
- Warnings: CNS effects, and in metronidazole = aseptic meningitis, encephalopathy, optic neuropathy
- Side Effects: Metallic tast, Headache, nausea, furry tongue, dark urine
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Metronidazole Drug Interactions
- Should not be used with alcohol (during and for 3 days after discontinuation of treatment) due to a potential disulflram-like reaction (ie. cramping, headache, N/V, flushing
- Metronidazole is weak inhibitor of CYP2C9 and can cause increase in INR in patients taking warfarin
141
# MISC ABX
**Lefamulin** (Xenleta): general MOA, dosage forms, dosing, contraindications, warnings, side effects, approved for what disease
- MOA: Lefamulin is a first-in-class pleuromutilin. It inhibits bacterial protein synthesis by binding to the peptidyl transferase center of the 50S ribosomal subunit.
- Tablet/ Injection: PO 600mg Q12h; IV 150mg Q12h
- CI: Use with CYP3A4 substrates that prolong the QT interval
- Warning: Avoid in preg, prolong QT, CDiff
- SEs: D/N, injection site rxn
- Approved for CAP
142
# MISC ABX
**Fidaxomicin**: Brand, dosage form, dosing, warning, side effects
- Brand: Dificid
- Tablet: PO 200mg BID x 10 days; no renal adj
- Warning: Not effective for systemic infections
- SEs: N/V, abdonimal pain, GI bleed, anemia
143
# MISC ABX
**Rifaximin**: Brand, dosage form, dosing for each disease states, side effects, notes
- Brand: Xifaxan
- Dosing: Travelers Diarrhea - PO 200mg TID x 3 days; Decrease recurrance of hepatic enceph - PO 550mg BID; IBS w diarrhia - 550mg TID x 14 days
- SEs: Peripheral edema, dizziness, headache, fart, nausea, abdominal pain, rash
- Note: not effective for systemic infection! used off lable for C.Diff
144
# Urinary Agent
**Fosfomycin**: MOA, brand name, dosage form, dosing, side effect, note
- MOA: Inhibits bacterial cell wall synthesis by inactivating the enzyme pyruval transferase, which is critical in the synthesis of cell walls. It covers E. coli (including ESBLs) and E. faecalis (including VRE). A single-dose regimen is used for uncomplicated UTI
(cystitis only).
- Brand: Monurol
- Packet granules = 3 grams per packet
- Dosing: 3 grams PO x 1 mixed in cold water (female uncomplicated UTI)
- SEs: Headache, diarrhea, nausea
- Notes: Concentrated in urine
145
# Urinary Agents
**Nitrofurantoin**: MOA, brand name, dosage form, dosing, contraindications, warning, side effect, note
- MOA: Nitrofurantoin is a bacterial cell wall inhibitor . It is used for uncomplicated UTI (cystitis only). It covers E. coli, Klebsiella, Enterobacter, S. aureus and Enterococcus (VRE)
- Brand: Macrodantin; Macrobid
- Capsule/ suspension
- Macrodantin - PO: 50-100mg QID x 3-7 days; 50-100mg QHS for prophylaxis
- Macro**bid** - PO: 100mg **BID** x 5 days
- Contraindication: renal inpairment (CrCL: less than 60) - inadeq urine concentrations and risk accumulation of neurotox; hx of jaundice
- Warning: Optic neuritis, hepatotoxicity, peripheral
neuropathy, pulmonary toxicity, hemolytic
anemia (use caution in patients with G6PD
deficiency)
- SEs: GI upset (take with food), headache, rash,
brown urine discoloration (harmless)
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# COMMONLY USED DRUGS FOR SPECIFIC PATHOGENS
MSSA
- Dicloxacillin, nafcillin, oxacillin
- Cefazolin, cephalexin (and other 1st and 2nd generation cephalosporins)
- Amoxicillin/clavulanate, ampicillin/ sulbactam
147
# COMMONLY USED DRUGS FOR SPECIFIC PATHOGENS
MRSA
- Vancomycin (consider using alternative
if MIC > 2)
- Linezolid
- Daptomycin (not in pneumonia!)
- Ceftaroline
- SMX/TMP (CA-MRSA SSTIs)
- Doxycycline, Minocycline (CA-MRSA SSTIs)
- Clindamycin (CA-MRSA SSTIs)
148
# COMMONLY USED DRUGS FOR SPECIFIC PATHOGENS
Vancomycin-resistant Enterococcus (VRE)
- Pen G or Ampicillin (E. Faecalis only)
- Linezolid
- Daptomycin
- Nitrofurantoin, fosfomycin, doxycycline (Cysitis only!)
149
# COMMONLY USED DRUGS FOR SPECIFIC PATHOGENS
Atypical Organism
- Azithromycin, Clarithromycin
- Doxycycline, Minocycline
- Quinolones
150
# COMMONLY USED DRUGS FOR SPECIFIC PATHOGENS
HNPEK: H. influenzae. Neisseria gonorrhoeae. Proteus. E. coli. Klebsiella
- Beta-lactam/beta-lactamase inhibitor
- Cephalosporins (except 1" generation)
- Carbapenems
- SMX/TMP
- Aminoglycosides
- Quinolones
151
# COMMONLY USED DRUGS FOR SPECIFIC PATHOGENS
Pseudomonas Aeruginosa
- Piperacillin/Tazobactam
- Cefepime
- Ceftazidime
- Ceftazidime/ Avibactam
- Ceftolozane/Tazobactam
- Carbapenems (except ertapenem)
- Ciprofloxacin, levofloxacin
- Artreonam
- Aminoglycosides
- Tobramycin
- Colistimethate, polymyxin 8
152
# COMMONLY USED DRUGS FOR SPECIFIC PATHOGENS
CAPES: Citrobacter, Acinetobacter, Providencia, Enterobacter, Serratia
- Pip/Taz
- Cefepime
- Carbapenems
- Aminoglycosides
- Colistimethate, Poly B
153
# COMMONLY USED DRUGS FOR SPECIFIC PATHOGENS
Extended-Spectrum Beta-Lactamase (ESBL) Producing Gram-Negative Rods: E.Coli, K. pneumoniae, P.mirabilis
- Carbapenems
- Ceftazidime/avibactam
- Ceftolozone/tazobactam
154
# COMMONLY USED DRUGS FOR SPECIFIC PATHOGENS
Carbapenem-resistant gram-negative rods (CRE)
- Ceftazidime/Avibactam
- Colistimethate, polymyxin B
- Meropenem/vaborbactam
- Impipenem/cilastatin/relebactam
155
# COMMONLY USED DRUGS FOR SPECIFIC PATHOGENS
Gram-Negative Anaerobes (Bacteroides fragilis)
- Metronidazole
- Beta-lactam/beta-lactamase inhibitor
- Cefotetan, cefoxitin
- Carbapenems
- Moxifloxacin (reduced activity)
156
# COMMONLY USED DRUGS FOR SPECIFIC PATHOGENS
C.Difficile
- Vancomycin (oral)
- Fidaxomicin
- Metronidazole
157
Most ABX are cleared through kidneys and require dose adj. **LIST THE ABX THAT DO NOT REQUIRE RENAL ADJUSTMENTS**
- Anti staphylococcal penicillins (e.g., dicloxacillin , nafcillin)
- Ceftriaxone
- Clindamycin
- Doxycycline
- Macrolides (azithromycin and erythromycin only)
- Metronidazole
- Moxifloxacin
- Linezolid
- Chloramphenicol
- Fidaxomicin
- Select tetracyclines (e.g., eravacycline, seracycline, omadacycline)
- Quinupristin/Dalfopristin
- Rifaximin
- Rifampin
- Tedizolid
- Tigecycline
- Tinidazole
- Vancomycin (PO only)
158
# Special Requirement ABX
Take with/ without food
Most abx can be taken with food to decrease GI issues.. The following are exceptions
- Take on an empty stomach: ampicillin oral capsules and suspension, levofloxacin oral solution, penicillin VK, rifampin , isoniazid, itraconazole solution, voriconazole
- Take within one hour of finishing a meal: amoxicillin ER
159
# Special Requirement ABX
**1:1 IV to Oral Dosing**: For these drugs, IV and oral dosing are the same
- Levofloxacin , moxifloxacin
- Doxycycline , minocycline
- Sulfamethoxazole/Trimethoprim
- Linezolid, tedizolid
- Metronidazole
- Fluconazole, isavuconazonium , posaconazole (oral tablets and IV), voriconazole
160
# Special Requirement ABX
LIGHT PROTECTION DURING ADMINISTRATION
- Doxycycline
- Micafungin
- Pentamidine
161
# Special Requirement ABX
DILUENT COMPATIBILITY REQUIREMENTS: Compatible with dextrose only
- Quinupristin/Dalfopristin
- Sulfamethoxazole/Trimethoprim
- Amphotericin B (conventional , Abelcet, Ambisome)
- Pentamidine
162
# Special Requirement ABX
DILUENT COMPATIBILITY REQUIREMENTS: Compatible with saline only
- Ampicillin
- Ampicillin/Sulbactam
- Ertapenem
- Daptomycin (Cubicin RF)
163
# Special Requirement ABX
DILUENT COMPATIBILITY REQUIREMENTS: Compatible with NS/LR only
- Caspofungin
- Daptomycin (Cubicin)
164
Key Counseling Points: All ABX
■ Proper storage (refrigeration or room temperature) and administration (with or without food) is essential.
■ Shake suspensions well.
■ Antibiotics treat bacterial infections. They do not treat viral infections, such as the common cold.
■ Complete the full course of therapy even if symptoms improve.
■ Measure liquid doses carefully using the measuring
device/syringe that comes with the medication. Do not use household spoons.
■ Some oral liquid and chewable dosage forms contain phenylalanine. Do not use if you have phenylketonuria (PKU).
■ Can cause:
o Rash.
o Nausea.
o Diarrhea, including Clostridium (Clostridioides)
difficile-associated diarrhea (with abdominal pain,
cramps and watery or bloody stool).
165
Key Counseling Points: Quinolones
■ Can cause:
o CNS effects, including seizures.
o Hypo/hyperglycemia.
o Peripheral neuropathy.
o Photosensitivity.
o QT prolongation.
o Tendon inflammation (tendinitis) or tendon rupture.
Can present with a "pop" or pain/swelling in the back
of the ankle (Achilles), shoulder or hand.
■ Avoid in pregnancy, breastfeeding and children.
■ Drug interactions due to binding.
166
Key Counseling Points: Macrolides
MACROLIDES
■ Can cause:
o Gl upset.
o QT prolongation.
Azithromycin (Zithromax)
■ Z-Pak: take two tablets on day 1, followed by one tablet daily on days 2-5.
167
Key Counseling Points: Tetracyclines
TETRACYCLINES
■ Avoid in pregnancy, breastfeeding and children < 8 years old.
■ Drug interactions due to binding.
■ Can cause photosensitivity.
.
Doxycycline (oral)
■ Take with a full glass of water and remain upright for 30 minutes after the dose to avoid GI irritation.
168
Key Counseling Points: Sulfa/Trim (Bactrim)
■ Avoid in:
□ Pregnancy or breastfeeding.
□ Sulfa allergy.
■ Can cause:
□ Photosensitivity.
o Crystals in the urine. Take with a full glass of water.
169
Key Counseling Points: Metronidazole
METRONIDAZOLE (Flagyl)
■ Do not use any alcohol products while using this
medication, and for at least three days afterward.
■ Can cause:
o Nausea
o Metallic taste in the mouth
170
Key Counseling Points: Nitrofurantoin
■ Take with food to decrease nausea.
■ Can cause:
- Nausea
- Brown discoloration of urine (temporary and harmless).
171
Key Counseling Points: MUPIROCIN NASAL OINTMENT
■ Place ½ the ointment from the tube into one nostril and the other ½ into the other nostril. Press the nostrils at the same time and let go; do this many times (for about 1 minute) to spread the ointment into the nose.
■ Wash hands after use.
■ Can cause burning and itching in the nose.
- **This medication is used to eliminate MRSA colonization in the nares!**
