Infectious Diseases I Flashcards
1
Q
What are transmissible diseases that are spread from person to person referred to?
A
Communicable or contagious
2
Q
What are three primary factors that impact treatment decisions in infectious diseases?
A
The bug (pathogen), the drug (antibiotic) and the patient (host)
3
Q
What do infection characteristics include?
A
The infection site, infection severity and whether it is community- or hospital-acquired
*Infections that are hospital-acquired often involve MDR organisms
4
Q
How is the presence of an infection determined by?
A
By signs and symptoms
5
Q
What do antibiotic characteristics include?
A
The spectrum of activity and ability to penetrate the site of infection
6
Q
What are some patient characteristics that impact treatment choices?
A
Age, body weight, renal and hepatic function, allergies, recent antibiotic use, colonization with resistant bacteria, recent environmental exposure, vaccination status, pregnancy status, immune function and comorbid conditions
7
Q
What is considered when initiating empiric treatment?
A
This empiric treatment is usually broad-spectrum (covers several different types of bacteria) and is based on a best guess of the likely organisms causing the infection. Local resistance patterns and antibiotic use guidelines should be considered when selecting empiric treatment
8
Q
What are some common bacterial pathogens for CNS/meningitis?
A
Streptococcus pneumoniae, neisseria meningitis, Haemophilus influenzae, group B streptococcus/e. coli (young), listeria (young/old)
9
Q
What are some common bacterial pathogens for upper respiratory?
A
Streptococcus pyogenes, streptococcus pneumoniae, haemophilus influenzae, moraxella catarrhalis
10
Q
What are some common bacterial pathogens for heart/endocarditis?
A
Staphylococcus aureus, streptococcus pyogenes, staphylococcus epidermidis, pasteureall multocida
11
Q
What are some common bacterial pathogens for bone/joint?
A
Staphylococcus aureus, staphylococcus epidermidis, streptococci, neiserria gonorrhoeae, GNR
12
Q
What are some common bacterial pathogens for mouth?
A
Mouth flora, anaerobic GNR, viridans group Streptococci
13
Q
What are some common bacterial pathogens for lower respiratory?
A
Streptococcus pneumoniae, haemophilus influenzae, atypicals (legionella, mycoplasma), chlamydophilia, enteric GNR (alcoholics)
14
Q
What are some common bacterial pathogens for lower respiratory?
A
Staphyloccocus aureus, including MRSA, pseudomonas aeruginasa, acinetobacter bamannii, enteric GNR (including ESBL, MDR), streptococcus pneumoniae
15
Q
What are some common bacterial pathogens for urinary tract?
A
E. coli, proteus, klebsiella, staphylococcus saprophyticus enterococci
16
Q
What is the purpose of the gram stain?
A
The Gram stain categorizes the organism by shape and provides quick, preliminary results. It provides a clue about what organism may be causing the infection ad an opportunity to adjust the empiric antibiotic regimen before the species is formally identified
17
Q
Describe gram-positive organisms
A
Have a thick cell wall and stain dark purple or bluish from the crystal violet stain
*Staphylococcus (including MRSA, MSSA), step pneumoniae, streptococcus, enterococcus, listeria monocytogenes, corynebacterium, peptostreptococcus, propionbacterium acnes, clostridiodes
18
Q
Describe gram-negative organisms
A
Have a thin cell wall and take up the safranin counterstain, resulting in a pink or reddish color
*Includes Neisseria spp, proteus mirabilis, e coli, klebsiella, serratia, enterobacter, citrobacter, acinetobacter, bordetella, moraxella, pseudomonas, haemophilus influenzae, providencia
19
Q
Describe atypical organisms
A
Do not have a cell wall and do not stain well
*Includes: chlamydia supp., legionella spp, mycoplasma pneumoniae, mycobacterium tuberculosis
20
Q
What does an antibiogram show?
A
An antibiogram combines culture data from patients at a single institution into one chart to show susceptibility patterns over a specific time period (generally 1 year). Antibiograms aid in selecting empiric treatment and are used to monitor resistance trends over time
21
Q
How soon is a culture and susceptibility report usually available?
A
Within 24-72 hours
22
Q
What is the purpose of C&S report?
A
The C&S report identifies the organism and the results of the susceptibility testing. The empiric antibiotics can then be streamlined, which can include discontinuing one or more antibiotics and/or changing to a more narrow-spectrum treatment
23
Q
What is the minimum inhibitory concentration (MIC)?
A
The minimum concentration of each antibiotic that inhibits bacterial growth. MICs are specific to each antibiotic and organism and should not be compared among different antibiotics
24
Q
What is the susceptibility breakpoint?
A
The usual drug concentration that inhibits bacterial growth
25
What can the effect of two antibiotics cause?
The effect of two additive antibiotics can be additive (an effect equal to the sum of the individual drugs) or synergistic (an effect greater than the sum of the individual drugs)
26
What are the steps and approach to prescribing antibiotic treatment?
1) Empiric treatment: select empiric treatment based on the likely organisms at the infection site
2) Streamline: when the C&S results are available, streamline to more narrow-spectrum antibiotics as soon as possible
3) Assess the patient: monitor for improvement and patient's condition
27
How can you monitor treatment response?
- Clinical status: fever trend and other vital signs depending on the infection, WBC trend, reduction in signs and symptoms of infection
- Radiographic findings (such as chest x-ray results)
- Repeat cultures negative
- Decreased markers of inflammation: procalcitonin levels, C-reactive protein and erythrocyte sedimentation rate
28
What are some reasons for lack of response of treatment?
- Antibiotic factors: inadequate spectrum and/or dose, poor tissue penetration, drug-drug interactions, non-adherence, inadequate duration of treatment, inability to tolerate/toxicity
- Microbiologic factors: resistance, superinfection (C. difficile), alternative etiology
- Host factors: uncontrolled source of infection, immunocompromisedq
29
What is antibiotic resistance?
Antibiotic resistance is the ability of an organism to multiply in the presence of a drug that normally limits its growth or kills it. These infections are difficult to treat ad often require drugs that are costly and/or toxic
30
What are common mechanisms of resistance?
Intrinsic resistance, selection pressure, acquired resistance, enzyme inactivation
31
Describe intrinsic reistance
The resistance is natural to the organism
32
Describe selection pressure
Resistance occurs when antibiotics kill off susceptible bacteria, leaving behind more resistant strains to multiplyf
33
Describe acquired resistance
Bacterial DNA containing resistant genes can be transferred between different species and/or picked up from dead bacterial fragments
34
Describe enzyme inactivation
Enzymes produced by bacteria break down the antibiotic
35
What are some examples to combat enzyme inactivation of antibiotics?
- Bacteria that product beta-lactamases break down beta-lactams before they can bind to their site of activity. Beta-lactamase inhibitors are combined with some beta-lactams to preserve or increase their spectrum of activity
- 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 cephalosporin/beta-lactamase inhibitors
- Carbapenem-resistant Enterobacteriaceae are MDR gram-negative organisms that produce enzymes capable of breakdown penicillins, most cephalosporins and carabpenems. CRE infections typically require treatment with a combination of antibiotics that include drugs such as the polymyxins, which have a high risk for toxicity
36
What are some common resistant pathogens?
- Klebsiella pneumoniae (ESBL, CRE)
- Escherichia coli (ESBL, CRE)
- Acinetobacter baumannii
- Enterococcus faecalis, enterococcus faecium (VRE)
- Staphyloccocus aureus (MRSA)
- Pseudomonas aeruginosa
37
What is the pathophysiology of clostridiodes difficile infection?
Antibiotics kill normal, healthy GI flora along with pathogens they are targeting, which results in overgrowth of drug-resistant organisms and can lead to superinfections such as C diff. Inactive C diff spores are present in normal GI flora. When an antibiotic kills off the normal flora, C. diff spores can become activated, producing toxins that inflame the GI mucosa
38
What are some symptoms of C. diff?
Symptoms can be mild (loose stools and abdominal cramping) to severe (pseudomembranous colitis that can require colectomy and can be fatal)
39
Which antibiotics have the highest risk of CDI?
All antibiotics have a warning for the risk of CDI, but the risk is highest with broad-spectrum penicillins and cephalosporins, quinolones, carbapenems and clindamycin (which has a boxed warning)
40
What is the purpose of antimicrobial stewardship programs (ASPs)?
Designed to improve patient safety and outcomes, curb resistance, reduce adverse effects and promote cost-effectiveness
41
What do ASPs do?
ASPs consist of collaborative teams that establish antibiotic guidance for their facility. ASPs conduct audits of prescribing habits and provide education to change suboptimal practices and improv care
42
What are some examples of ASP interventions?
Pharmacokinetic monitoring of aminoglycosides and vancomycin, use of clinical decision support software to rapidly identify pathogens and shorten the time to starting effective treatment, preauthorization of select antimicrobials, prospective audit and feedback to prescribers of selected antibiotics and timely transitions from IV to PO antibiotics
43
What are the general antibiotic mechanisms of action?
Generally, cell wall and cell membrane inhibitors, DNA/RNA inhibitors and aminoglycosides are bactericidal (kill bacteria), while most protein and folic acid synthesis inhibitors are bacteriostatic (inhibit bacterial growth)
44
What are some examples of DNA/RNA inhibitors?
Quinolones (DNA gyrase, topoisomeraise IV), Metronidazole, tinidazole, rifampin
45
What are some examples of folic acid inhibitors?
Sulfonamides, trimethoprim, Dapsone
46
What are some examples of cell wall inhibitors?
Beta-lactams (penicillins, cephalosporin, carbapenems), monobactams (aztreonam), vancomycin, dalbavancin, telavancin, oritavancin
47
What are some examples of protein synthesis inhibitors?
Aminoglycosides, macrolides, tetracyclines, clindamycin, linezolid, tedizolid, quinupristin/dalfopristin
48
What are some examples of cell membrane inhibitors?
Polymyxins, daptomycin, telavancin, oritavancin
49
What are some examples of hydrophilic agents?
Beta-lactams, aminoglycosides, glycopeptides, daptomycin, polymyxins
50
What are some PK parameters considered with hydrophilic agents?
1) Small distribution: poor tissue penetration
2) Renal elimination: drug accumulation and side effects can occur if not dose adjusted
3) Low intracellular concentrations: not active against atypical (intracellular) pathogens
4) Increased clearance and/or distribution in sepsis: consider loading doses and aggressive dosing in sepsis
5) Poor-moderate bioavailability: not used PO or IV:PO ratio is not 1:1
51
What are some examples of lipophilic agents?
Quinolones, Macrolides, Rifampin, Linezolid, Tetracyclines
52
What are some PK parameters considered with lipophilic agents?
1) Large volume of distribution: excellent tissue penetration (including bone, lung and brain tissues)
2) Hepatic metabolism: potential for hepatotoxicity and drug-drug interactions
3) Achieve intracellular concentrations: active against atypical (intracellular) pathogens
4) Clearance/distribution is changed minimally in sepsis: dose adjustments generally not needed in sepsis
5) Excellent bioavailability: IV:PO ratio is often 1:1
53
How can drugs with concentration-dependent killing be dose optimized?
Can be dosed less frequently and in higher doses to maximize the concentration above the MIC
54
How can drugs with time-dependent killing be dose optimized?
Can be dosed more frequently or administered for a longer duration to maximize the time above the MIC
55
What are some examples of antibiotics that are concentration-dependent?
Aminoglycosides, quinolones, daptomycin
56
What are some examples of antibiotics that are exposure-dependent?
Vancomycin, macrolides, tetracyclines, polymyxins
57
What are some examples of antibiotics that are time-dependent?
Beta-lactams (penicillins, cephalosporins, carbapenems)
58
What is the MOA of beta-lactam antibiotics?
Beta-lactam have a chemical structure that is characterized by a beta-lactam ring. They inhibit bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs) which prevents the final step of peptidoglycan synthesis in bacterial cell walls
59
What bacteria are penicillins not active against?
Atypicals or MRSA
60
What are natural penicillins active against?
Natural penicillins are active against Gram-positive cocci (Streptococci and Enterococci; they do not cover Staphylococci) and Gram-positive anaerobes (mouth flora). They have no appreciable Gram-negative activity
61
What do antistaphylococcal penicillins cover?
Streptococci and have enhanced activity against methicillin-susceptible Staphylococcus aureus (MSSA), but they lack activity against Enterococcus, gram-negative pathogens and anaerobes
62
What do aminopenicillins cover?
Aminopenicillins cover Streptococci, Enterococci and gram-positive anaerobes (mouth flora) plus (with the addition of the amino group) the gram-negative bacteria Haemophilus, Neisseria, Proteus and E. coli
*Aminopenicllins combined with beta-lactamase inhibitors have added activity against MSSA, more resistant strains of gram-negative bacteria and gram-negative anaerobes
63
What do extended-spectrum penicillins, combined with a beta-lactamase inhbitor cover?
Broad spectrum activity: cover same organisms as aminopenicillin/beta-lactamase inhibitor combinations plus have expanded coverage of other gram-negative bacteria, including Citrobacter, Acinetobacter, Providencia, Enterobacter, Serrata and Pseudomonas aeruginosa
64
What are some examples of natural penicillins?
Penicillin V potassium, Penicillin G aqueous, Penicillin G Benzathin
65
What are some examples of antistaphylococcal penicillins?
Dicloxacillin, Naficillin, Oxacillin
66
What are some examples of aminopenicillins?
Amoxicillin, Augmentin, Ampicillin, Unasyn
67
What are some examples of extended-spectrum penicillins?
Piperacillin/Tazobactam (Zosyn)
68
What is a boxed warning associated with penicillins?
Penicillin G benzathine: not for IV use; can cause cardio-respiratory arrest and death
69
What are some contraindications within the penicillin class?
- Augmentin and Unasyn: history of cholestatic jaundice or hepatic dysfunction associated with previous use
- Severe renal impairment (CrCL < 30 mL/min): do not use extended-release oral forms of amoxicillin and Augmentin XR or the 875 mg strength of augmentin
70
What are some side effects of penicillins?
Seizures (with accumulation when not correctly dose adjusted in renal dysfunction), GI upset, diarrhea, rash (including SJS/TEN)/allergic reactions/anaphylaxis, hemolytic anemia (identified with a positive Coombs test), renal failure, myelosuppression with prolonged use, increased LFTs
71
What are some monitoring parameters of penicillins?
Renal function, symptoms of anaphylaxis with the first dose, CBC and LFTs with prolonged courses
72
What are some notes about antistaphylococcal penicillins?
- Preferred for MSSA soft tissue, bone and joint, endocarditis and bloodstream infections
- No renal dose adjustments
- Nafcillin is a vesicant: administration through a central line is preferred; if extravasation occurs, use cold packs and hyaluronidase injections
73
What are some notes about aminopenicillins?
- Aminopenicillin PO is rarely used due to poor bioavailability; amoxicillin is preferred if switching from IV ampicillin
- Amoxicillin/clavulanate: use a 14:1 ratio to decrease diarrhea caused by the clavulanate component
- IV ampicillin and ampicillin/sulbactam must be diluted in NS only
74
What is a note about extended-spectrum penicillins?
Piperacillin/tazobactam contains 65 mg Na per 1 gram of piperacillin
75
What are some examples of penicillin drug interactions?
- Probenecid can increase the levels of beta-lactams by interfering with renal excretion and 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 can inhibit the anticoagulant effect of warfarin
- Penicillins can increase the serum concentration of methotrexate; they can decrease the serum concentration of mycopheolate active metabolites due to impaired enterohepatic recirculation
76
What are the class effects of penicillins?
- All penicillins should be avoided in patients with a beta-lactam allergy (Exception: treatment of syphilis during pregnancy and in HIV patients with poor compliance/follow-up desensitize and treat with penicillin G benzathine
- All penicillins increase the risk of seizures if accumulations occurs
77
What are some examples of penicillins that can be taken outpatient (oral)?
Pencillin VK, Amoxicillin, Augmentin, Dicloxacillin
78
What is a note specific to Penicillin VK?
A first-line treatment for strep throat and mild nonpurulent skin infections (no abscess)
79
What are some notes specific to Amoxicillin?
- First-line treatment for acute otitis media
- Drug of choice for infective endocarditis prophylaxis before dental procedures
- Used in H. pylori treatment
80
What are some notes specific to Augmentin?
- First line treatment for acute otitis media and for sinus infections (if antibiotics indicated)
- Use the lowest dose of clavulanate to decrease diarrhea
81
What are some notes specific to Dicloxacillin?
- Covers MSSA only
| - No renal dose adjustment needed
82
What are cephalosporins not active against?
Enterococcus spp. or atypical organisms
83
Describe the spectrum of activity of first generation cephalosporins
Excellent activity against gram-positive cocci (e.g. Streptococci and Staphylococci) and preferred when a cephalosporin is used for MSSA infections. They have some activity against the gram-negative rods Proteus, E. coli and Klebsiella (PEK), but in general, gram-negative activity is decreased compared to 2nd, 3rd and 4th generation cephalosporins
84
Describe the spectrum of activity of second generation cephalosporins
Drugs such as cefuroxime cover Staphyloccoci, more resistant strains of S, pneumoniae plus Haemophilus, Neisseria, Proteus, E. coli and Klebsiella. Cefotetan and cefoxitin, have added coverage of gram-negative anaerobes (B. fraqilis)
85
Describe the spectrum of activity of third generation cephalosporins
- Group 1 includes ceftriaxone, cefotaxime and oral drugs which cover resistant Streptococci (S, pneumoniae and viridans group Streptococci), Staphylococci (MSSA), gram-positive anaerobes (mouth flora) and resistant strains of HNPEK
- Group 2 includes ceftazidime, which lacks gram-positive activity but covers Pseudomonas
86
Describe the spectrum of activity of fourth-generation cephalosporins
Only includes cefepime, which has broad gram-negative activity (HPNEK, CAPES and Pseudomonas) and gram-positive activity similar to ceftriaxone
87
Describe the spectrum of activity of fifth generation cephalosporins
Only includes ceftaroline which has gram-negative activity similar to ceftriaxone, but broad gram-positive activity; it is the only beta-lactam that covers MRSA
88
Describe the spectrum of activity of other cephalosporins
- Beta lactamase inhibitor combinations: ceftazidime/avibactam and ceftolozane/tazobactam have a similar spectrum as ceftazadime but with added activity against MDR Pseudomonas and other MDR gram-negative rods
- Siderophore cephalosporin: cefiderocol uses the iron transport system to enter the gram-negative cell wall. It is approved for complicated UTI/pyelonephritis and active against E. coli, Enterobacter, Klebsiella, Proteus and Pseudomonas
89
What are the 1st generation cephalosporins?
Cefazolin, Cephalexin, Cefadroxil
90
What are the 2nd generation cephalosporins?
Cefuroxime, Cefotetan, Cefaclor, Cefotoxin, Cefprozil
91
What are the 3rd generation group 1 cephalosporins?
Cefdinir, Ceftriaxone, Cefotaxime, Cefditoren, Cefixime, Cefpodoxime, Ceftibuten
92
What is the 3rd generation group 2 cephalosporin?
Ceftazadime
93
What is a 4th generation cephalosporin?
Cefepime
94
What is a 5th generation cephalosporin?
Ceftaroline fosamil
95
What are the cephalosporin combinations?
Ceftazidime/Avibactam, Cetolozane/Tazobactam
96
What is a siderophore cephalosporin?
Cefiderocol
97
What are some contraindications to Ceftriaxone?
- Hyperbilirubinemia neonates (causes biliary sluding, kenicterus)
- Concurrent use with calcium-containing IV products in neonates < 28 days old
98
What are some warnings associated with cephalosporins?
- Cross sensitivity with PCN allergy (< 10% higher risk with first generation cephalosporins); do not use in patients with type 1 hypersensitivity to PCN (swelling, angioedema, anaphylaxis)
- Cefotetan contains a side chain, which can increase the risk of bleeding and cause a disulfiram-like reaction with alcohol ingestion
- Anaphylaxis/hypersensitivity reactions
- Some drugs can increase INR in patients taking warfarin
99
What are some side effects of cephalosporins?
Seizures (with accumulation when not correctly dose adjusted in renal dysfunction), GI upset, diarrhea, rash/allergic reactions/anaphylaxis, acute interstitial nephritis, hemolytic anemia (identified with a positive Coombs test), myelosuppression with prolonged use, increased LFTs, drug fever, serious skin reactions (SJS/TEN)
100
What are some monitoring parameters of cephalosporins?
Renal function, signs of anaphylaxis with first dose, CBC, LFTs
101
What are some notes about Ceftriaxone?
No renal adjustment, CNS penetration at high doses when meninges inflamed
102
What is a note about Cefixime?
Cefixime available in a chewable tablet
103
What is a note about Cefixime/avibactam?
Activity against some carbapenem-resistant Enterobacteriaceae
104
What is a note about Cefiderocol?
Increase to 2 grams Q6H if CrCl > 120 mL/min
105
What are some key cephalosporin drug interactions?
- Drugs that decrease stomach acid can decrease the bioavailability of some oral cephalosporins. Cefuroxime, cefpodoxime, cefdinir and cefditoren should be separated by two hours from short-acting antacids, H2Ras and PPIs should be avoided
- Insoluble precipitates may form when ceftriaxone is administered with calcium-containing IV fluids (do not use together in neonates). In adults, IV line should be flushed with a compatible fluid between administration of each product
106
What are some class effects of cephalosporins?
- Due to a small risk of cross-reactivity, do not choose a cephalosporin on the exam if the patient has a penicillin allergy (exception: pediatric patients with acute otitis media)
- Risk of seizures if accumulation occurs (e.g. failure to dose adjust in renal dysfunction)
107
What is cephalexin typically used for?
Skin infections (MSSA), strep throat
108
What is Cefuroxime commonly used for?
Acute otitis media, community-acquired pneumonia (CAP), sinus infection (if antibiotics indicated)
109
What is cefdinir commonly used for?
CAP, sinus infection (if antibiotics indicated)
110
What is Cefazolin typically used for?
Surgical prophylaxis
111
What is Cefotetan and Cefoxitin commonly used for?
- Anaerobic coverage (B. fragilis)
- Common use: surgical prophylaxis (colorectal procedures)
- Cefotetan can cause a disulfiram-like reaction with alcohol ingestion
112
What is Ceftriaxone and Cefotaxime?
- Common uses: CAP, meningitis, spontaneous bacterial peritonitis, pyelonephritis
- Ceftriaxone: no renal dose adjustment, do not use ceftriaxone in neonates (Age 0-28 days)
113
What is Ceftazidime and Cefepime active against?
Pseudomonas
114
What is Ceftolozane/Tazobactam and Ceftazidime/Avibactam active against?
Used for MDR gram-negative organisms (including Pseudomonas)
115
What is Ceftaroline commonly used for?
CAP, skin and soft tissue infections
116
What are carbapenems reserved for?
Carbapenems are very broad-spectrum antibiotics that are generally reserved for MDR gram-negative infections. They are active against most gram-positive, gram-negative (includes ESBL-producing bacteria) and anaerobic pathogens. They provide no coverage of atypical pathogens, MRSA, VRE, C. difficile or Stenotrophomonas
117
How is Ertapenem different from other carbapenems?
Ertapenem is different from other carbapenems as it has no activity against Pseudomonas, Acinetobacter or Enterococcus
118
What are carbapenem/beta-lactamase inhibitor combinations typically reserved for?
Highly resistant infections (CRE) that are not able to be treated with a single entity carbapenem
119
What are some examples of carbapenems?
Doripenem, Imipenem/Cilastatin, Meropenem, Ertapenem
120
What are contraindications of carbapenems?
Anaphylactic reactions to beta-lactam antibiotics
121
What are some warnings associated with carbapenems?
- Do not use in patients with PCN allergy (small risk of cross-reactivity)
- CNS adverse effects, including states of confusion and seizures
- Doripenem: do not use for the treatment of pneumonia, including healthcare-associated pneumonia (HAP) and ventilator-associated pneumonia (VAP)
122
What are some side effects associated with carbapenems?
Diarrhea, rash/severe skin reaction (DRESS), seizures with higher doses and in patients with impaired renal function (mainly imipenem), bone marrow suppression with prolonged use, increased LFTs
123
What are some monitoring parameters of carbapenems?
Renal function, symptoms of anaphylaxis with first dose, CBC, LFTs
124
What is a note associated with Imipenem?
Imipenem is combined with cilastatin to prevent drug degradation by renal tubular dehydropeptidase
125
What is Ertapenem commonly used for?
Commonly used for diabetic foot infections
126
What are some significant carbapenem drug interactions?
- Carbapenems can decrease serum concentrations of valproic acid, leading to a loss of seizure control
- Use with caution in patients with a history of seizure disorder, or in combination with other drugs known to lower the seizure threshold
127
What are some class effects of carbapenems?
- All active against ESBL-producing organisms and (except Ertapenem) Pseudomonas
- Do not use with penicillin allergy
- Seizure risk (with higher doses, failure to dose adjust in renal dysfunction, or use of imipenem/cilastatin
128
What are carbapenems commonly used for?
- Polymicrobial infections
- Empiric therapy when resistant organisms suspected
- ESBL-positive infections
- Resistant Pseudomonas or Acinetobacter infections (except ertapenem)
*All are IV only. Ertapenem must be diluted in normal saline
129
What is the MOA of Aztreonam?
Aztreonam has a mechanism of action similar to beta-lactams; it inhibits bacterial cell wall synthesis by binding to penicillin-binding proteins (PBPs), which prevents the final step of peptidoglycan synthesis in bacterial cell walls
130
What is Aztreonam reserved for?
Aztreonam covers many gram-negative organisms, including Pseudomonas. It has no gram-positive or anaerobic activity
131
What are some side effects associated with Aztreonam?
Similar to penicillins, including rash, N/V/D, increased LFTs
132
What is a note associated with Aztreonam?
Can be used with a penicillin allergy
133
What is the MOA of aminoglycosides?
Aminoglycosides bind to the ribosome, which interferes with bacterial protein synthesis and results in a defective bacterial cell membrane
134
What are aminoglycosides active against?
They are active against gram-negative bacteria (including Pseudomonas) and are primarily used as part of an empiric regimen with other antibiotics (general not used as monotherapy)
135
What are examples of aminoglycosides and its common uses?
- Gentamicin and streptomycin are used for synergy, in combination with a beta-lactam or vancomycin, when treating gram-positive infections. Streptomycin and amikacin are used as second line treatments for Mycobacterial infections
136
What are the two dosing strategies for aminoglycosides?
- Traditional dosing: uses lower doses more frequently
| - Extended interval dosing: uses higher doses less frequently
137
What is the advantage of extended interval dosing?
There is less accumulation of drug, lower risk of nephrotoxicity and decreased cost
138
What is the "good news" with regards to aminoglycosides?
Aminoglycosides kill gram-negative pathogens fast, are synergistic with beta-lactams for some gram-positive organisms and have low resistance and drug cost. They demonstrate concentration-dependent activity and have a post-antibiotic effect
139
What is the "bad news" associated with aminoglycosides?
They have notable toxicities that require monitoring: renal damage and ototoxicity, which may be irreversible (hearing loss/tinnitus/balance problems)
140
What are some examples of aminoglycosides?
Gentamicin, Tobramycin, Amikacin, Streptomycin, Plazomicin
141
What weight is used for aminoglycoside dosing?
- If underweight (< ideal body weight): use total body weight for dosing
- If normal weight: ideal body weigh or total body weight can be used for dosing
- If obese: use adjusted body weight for dosing
142
What is traditional aminoglycoside dosing?
- Gentamicin and tobramycin: 1-2.5 mg/kg/dose; lower doses are used from gram-positive infections; higher doses are used for gram-negative infections
- Amikacin: 5-7.5 mg/kg/dose Q8h
143
Describe the renal dose adjustments for traditional dosing
- CrCl > 60 mL/min: Q8h
- CrCl 40-60 mL/min: Q12h
- CrCL 20-40 mL/min: Q24 h
- CrCl < 20 mL/min: 1x dose, then dose per levels
144
What is the extended interval IV dosing of Gentamicin/Tobramycin?
- 4-7 mg/kg/dose (commonly 7 mg/kg)
- Frequency (dosing interval) is determined by a nomogram but starts at Q24h if the renal function is normal
- Avoid when clearance and/or volume of distribution are altered
145
What are some boxed warnings associated with aminoglycosides?
Nephrotoxicity, ototoxicity (hearing loss, vertigo, ataxia), neuromuscular blockade and respiratory paralysis, avoid with other neurotoxic/nephrotoxic drugs, fetal harm if given in pregnancy
146
What are some warnings associated with aminoglycosides?
Use caution in patients with impaired renal function in the elderly and those taking other nephrotoxic drugs
147
What are some side effects associated with aminoglycosides?
Nephrotoxicity (acute tubular necrosis), hearing loss (early toxicity associated with high-pitched sounds), vestibular toxicity (resulting in balance deficits)
148
What are some monitoring parameters of aminoglycosides?
- Drug levels, renal function, urine output, hearing tests
- Traditional dosing: draw a trough level right before the 4th dose; draw a peak level 30 minutes after the end of the 30 minute infusion for the 4th dose
- Extended interval dosing: draw a random level per the timing on the nomogram
149
What are some notes associated with aminoglycosides?
- Amikacin is the most active against Pseudomonas
- The clinical definition of obesity varies (but TBW > 120% IBW is commonly used for drug dosing)
- Plazomicin is reserved for MDR gram-negative UTIs and should only be used when there are no alternative treatment options
150
What is the goal peak level of gentamicin gram-positive infection?
3-4 mcg/mL
151
What is the goal trough level of gentamicin gram-positive infection?
< 1 mcg/mL
152
What is the goal peak level of gentamicin gram-negative infection and tobramycin?
5-10 mcg/mL
153
What is the goal trough level of tobramycin?
< 2 mcg/mL
154
What is the goal peak level of Amikacin?
20-30 mcg/mL
155
What is the goal trough level of Amikacin?
< 5 mcg/mL
156
What is the MOA of quinolones?
Quinolones inhibit bacterial DNA topoisomerase IV and DNA gyrase (topoisomerase II) inside the bacteria which prevents supercoiling of DNA and promotes breakage of double-stranded DNA
157
Describe the spectrum of activity of of quinolones
Quinolones have concentration-dependent antibacterial activity and a broad-spectrum of activity against a variety of gram-negative, gram-positive and atypical pathogens
158
Describe the spectrum of activity specific to Levofloxacin, Moxifloxacin and Gemifloxacin
Levofloxacin, moxifloxacin and gemifloxacin are referred to as respiratory quinolones due to enhanced coverage of S. pneumoniae and atypical pathogens
159
Describe the spectrum of ciprofloxacin and levofloxacin
Ciprofloxacin and levofloxacin have enhanced gram-negative activity, including activity against Pseudomonas. They may be used empirically in combination with another agent when Pseudomonas infections are suspected and as monotherapy, if the final C&S report indicates susceptibility
160
Describe the spectrum of activity of moxifloxacin
Moxifloxacin has enhanced gram-positive and anaerobic activity and can be used alone for polymicrobial infections. It is the only quinolone that cannot be used to treat urinary tract infections
161
Describe the spectrum of activity of Delafloxacin
Delafloxacin is active against MRSA and is the preferred quinolone if treating skin infections suspected to be caused by MRSA. Other quinolones should be generally be avoided due to high rates of MRSA resistance
162
What are some examples of quinolones?
Ciprofloxacin, Levofloxacin, Moxifloxacin, Delafloxacin, Gatifloxacin, Gemigfloxacin, Ofloxacin
163
What are some boxed warnings associated with quinolones?
- Tendon inflammation and/or rupture (often in the Achilles tendon) within hours/days of starting, or up to several months after completion of treatment, increased risk with concurrent use of systemic steroids, in organ transplant patients and age > 60 years. Discontinue immediately if symptoms occur
- Peripheral neuropathy; can last months to years after the drug has been discontinued and may become permanent. Discontinue immediately if symptoms occur
- CNS effects, paranoia, nightmares, insomnia, increased intracranial pressure (use caution inpatients with CNS disorders or with drugs that cause seizures or lower the seizure threshold
- 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 (do not use moxifloxacin)
164
What is a contraindication of ciprofloxacin?
Concurrent administration of tizanidine
165
What are some warnings associated with quinolones?
- QT prolongations (highest risk with moxifloxacin > levofloxacin > ciprofloxacin)
- Hypoglycemia and hyperglycemia
- Psychiatric disturbances
- Avoid systemic quinolones in children and in pregnancy/breastfeeding due to the risk of musculoskeletal toxicity (exception: for anthrax exposure)
- Aortic aneurysm and dissection
- Other: photosensitivity, headache, dizziness, serious skin reactions (SJS/TEN)
166
What are some notes about cipro oral suspension?
Shake vigorously for 15 seconds before each use. Do not put through a NG or other feeding tube (the oil-based suspension adheres to the tubing)
167
What are some notes about Cipro?
Can crush immediate-release tablets, mix with water and give via a feeding tube. Hold tube feedings at least 1 hour before and 2 hours after the dose
168
What are some notes about Moxifloxacin?
Moxifloxacin should not be used for UTIs (does not concentrate in the urine)
169
What are some key drug interactions of quinolones?
- Antacids and other polyvalent cations, multivitamins, sucralfate, and bile acid resins can chelate and inhibit quinolone absorption and should not be taken at the same time (separate administration)
- Lanthanum carbonate and sevelemar can decrease serum concentration of oral quinolones; separate administration by at least two hours before and at least two hours after or six hours after
- Quinolones can increase the effects of warfarin
- Quinolones can increase the effects of sulfonylureas, insulin and other hypoglycemic drugs
- Caution with CVD, decreased potassium and magnesium and with other QT-prolonging drugs
- Probenecid and NSAIDs can increase quinolone levels
- Cipro is a strong CYP1A2 inhibitor , a weak CYP3A4 inhibitor, and a P-glycoprotein (P-gp) substrate and can increase levels of caffeine, theophylline and tizanidine by reducing metabolism
170
What are some common uses of quinolones?
Can vary by agent; pneumonias, UTIs, intra-abdominal infections, travelers' diarrhea
171
What are common uses of respiratory quinolones?
Used for Pseudomonas infections
172
What is a special note about Moxifloxacin?
Only quinolone that is not really adjusted (do not use for UTIs)
173
What quinolones have an IV to PO ratio 1:1?
Levofloxacin and moxifloxacin
174
What conditions should be careful with use of quinolones?
- Caution with CVD, decreased K/Mg and with other QT-prolonging drugs
- Avoid in patients with seizure history if using seizure drugs
- Avoid in children
175
What are some counseling points of quinolones?
- Avoid sun exposure, separate from cations, monitor blood glucose (in diabetes)
- Watch for tendon rupture, neuropathy, CNS or psychiatric side effects
176
What is the MOA of Macrolides?
Macrolides bind to the 50S ribosomal subunit, resulting in inhibition of RNA-dependent protein synthesis
177
Describe the spectrum of activity of macrolides
They have excellent coverage of atypicals (Legionella, Chlamydia, Mycoplasma, Mycobacterium avium complex) and Haemophilus. Macrolides are treatment options for community-acquired upper and lower respiratory tract infections and certain sexually transmitted infections, but utility against S. pneumoniae, Haemophilus, Neisseria and Moraxella can be limited due to increasing resistance
178
What are some examples of Macrolides?
Azithromycin, Clarithromycin, Erythromycin
179
What are some contraindications of macrolides?
- 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
180
What are some warnings associated with macrolides?
- QT prolongation (highest risk with erythromycin > azithromycin > clarithromycin); avoid in patients with known QT prolongation, or those with additive risks
- Hepatotoxicity: use caution in patients with liver disease
- Exacerbation of myasthenia gravis
- Clarithromycin: caution in patients with CAD
181
What are some side effects associated with Macrolides?
GI upset, severe skin reactions (SJS/TEN/DRESS)
182
What are some key drug interactions of macrolides?
- Erythromycin and clarithromycin are major substrates of CYP3A4 and CYP3A4 inhibitors. Some medications metabolized by CYP3A4 should be avoided and others may require close monitoring, or should be used with caution in combination with erythromycin and clarithromycin
- Azithromycin is a minor substrate of CYP3A4 and a weak inhibitor of CYP1A2 and P-gp (fewer clinically significant drug interactions)
- All macrolides: use caution with CVD, decreased potassium and magnesium and with other QT-prolonging drugs
183
What are macrolides commonly used for?
- All macrolides: CAP, and as an alternative to a beta-lactam for strep throat
- Azithromycin: COPD exacerbations, chlamydia (as monotherapy), gonorrhea (in combination therapy), prophylaxis for MAC, severe travelers' diarrhea
- Clarithromycin: used in H. pylori treatment regimens
- Erythromycin: increase gastric motility
184
What is common azithromycin dosing?
Two 250 mg tablets PO x 1, then 250 mg PO daily x 4 days
185
What is the MOA of tetracyclines?
Tetracyclines inhibit bacterial protein synthesis by reversibly binding to the 30S ribosomal subunit
186
Describe the spectrum of activity of tetracyclines
They cover many gram-positive (Staphylococci, Streptococci, Enterococci, Propionbacterium spp), gram-negative bacteria, including respiratory flora (Haemophilus, Moraxella, atypicals) and other unique pathogens (e.g. Rickettsiaem Bacillus anthracis, Treponema pallidum, and other spirochetes)
187
What are the typical indications of Doxycycline?
Doxycycline has broader indications than the other tetracyclines, including respiratory tract infections, rick-borne/ricksettsial diseases, spirochetes and sexually transmitted infections (chlamydia and gonorrhea). It is an option for the treatment of mild skin infections caused by CA-MRSA and VRE urinary tract infections
188
What are some examples of tetracyclines?
Doxycycline, minocycline, ervacycline, omadacycline, sarecycline, tetracycline
189
What are some warnings associated with tetracyclines?
- Children < 8 years of age, pregnancy and breastfeeding (suppresses bone growth and skeletal development and permanently discolors teeth)
- Photosensitivity, tissue hyperpigmentation, severe skin reactions (DRESS/SJS/TEN), exfoliative dermatitis
- Gastrointestinal inflammation/ulceration
- Minocycline: drug-induced lupus erythematosus
190
What are some side effects associated with tetracyclines?
N/V/D, rash
191
What are some monitoring parameters of tetracyclines?
LFTs, renal function, CBC
192
What are some notes associated with tetracyclines?
- IV:PO ration is 1:1 (doxycycline, minocycline)
- Tablets and capsules should be taken with 8 oz of water; with doxycycline, sit upright for at least 30 minutes after dose to avoid esophageal irritation
193
What are some significant tetracycline drug interactions?
- Antacids and other polyvalent cations, multivitamins, sucralfate, bismuth subsalicylate and bile acid resins can chelate and inhibit tetracycline absorption. Separate doses of tetracyclines (1-2 hours before or hour hours after the chelating drugs). Dairy products should be avoided 1 hour before or two hours after tetracycline
- Lanthanum carbonate (Fosrenol) can decrease the concentration of tetracycline derivatives; take tetracycline at least 2 hours before or after lanthanum
- Tetracyclines is a major substrate of CYP3A4 and a moderate CYP3A4 inhibitor. Use caution with CYP3A4 inhibitors, which increase levels, and CYP3A4 inducer, which decrease levels
- Tetracyclines can enhance the effects of warfarin and neuromuscular blocking drugs
194
What are some common uses of tetracyclines?
- Doxycycline and minocycline: CA-MRSA skin infections, acne
- Doxycycline: first-line treatment for Lyme disease, Rocky Mountain Spotted Fever (tick-borne illnesses), CAP, COPD exacerbations, sinusitis (if antibiotic indicated), VRE UTI, chlamydia (as monotherapy), gonorrhea
- Tetracyclines: used in H. pylori treatment regimens
*Do not use in pregnancy, breastfeeding or children < 8 years old
195
What is the MOA of Sulfamethoxazole?
Sulfamethoxazole inhibits dihydrofolic acid formation from para-aminobenzoic acid, which interferes with bacterial folic acid synthesis
196
What is the MOA of trimethoprim (TMP)?
Trimethoprim inhibits dihydrofolic acid reduction to tetrahydrofolate, result in inhibition of the folic acid pathway
197
Describe the spectrum of activity of bactrim
Bactrim has activity against Staphylococci (including MRSA and CA-MRSA)l S. penumoniae and Group A Strep activity is unreliable. Activity against gram-negative bacteria is broad and includes Haemophilus, Proteus, E. coli, Klebsiella, Enterobacter, Shigella, Salmonella and Stenotrophomonas. It is active against some opportunistic pathogens but does not have activity against Pseudomonas, Enterococci, atypicals or anaerobes
198
What are contraindications of Bactrim?
Sulfa allergy, pregnancy (at term) and breastfeeding (block folic acid metabolism, leading to congenital defects), anemia due to folate deficiency, renal or hepatic disease, infants < 2 months
199
What are some warnings associated with Bactrim?
- Blood dyscrasias, including agranulocytosis and aplastic anemia
- Skin reactions: SJS/TEN/TTP
- G6PD deficiency: do not use with known deficiency and discontinue drug if hemolysis occurs
- Hypoglycemia, thrombocytopenia
200
What are some side effects associated with Bactrim?
Photosensitivity, increased K, hemolytic anemia, crystalluria, N/V/D, anorexia, skin rash, decreased folate, false elevations in SCr, renal failure
201
What are monitoring parameters of Bactrim?
Renal function, electrolytes, CBC, folate
202
What are some key Bactrim drug interactions?
- SMX/TMP is a moderate-strong CYP2C8 and CYP2C9 inhibitor and can cause significantly increase INR if used in combination with warfarin
- Levels of SMX/TMP can be decreased by CYP2C8 and CYP2C9 inducers
- SMX/TMP can enhance the toxic effects of methotrexate (therapeutic effects of SMX/TMP can be diminished by the use of leucovorin
- The risk of hyperkalemia will increase in patients with renal dysfunction or if used in combination with ACE inhibitors, ARBs, aliskiren, aldosterone receptor antagonists, potassium-sparing diuretics, cyclosporine, tacrolimus, NSAIDs, drospirenone-containing oral contraceptives or canagliflozin
203
What is Bactrim commonly used for?
CA-MRSA skin infections, UTI, Pneumocystis pneumonia (PCP)
204
What is the dose of TMP in SS tablet of Bactrim?
80 mg
205
What is the dose of TPM in double strength Bactrim?
160 mg
206
What is the MOA of Vancomycin?
Vancomycin is a glycopeptide that inhibits bacterial cell wall synthesis by binding to D-alanyl-D-alanine cell wall precursor and blocking peptidoglycan polymerization
207
Describe the spectrum of activity of Vancomycin
Vancomycin only covers gram-positive bacteria, including Staphylococci (MRSA), Streptococci, Enterococci (not VRE) and C. difficile (using the PO route only)
208
What are some warnings associated with Vancomycin?
- Ototoxicity and nephrotoxicity; caution with use of other nephrotoxic or ototoxic drugs or with prolonged high serum concentrations (dose adjustment required in renal impairment)
- PO formulation is only for C. difficile colitis and enterocolitis, not for systemic infections; IV formulation is not effective for C. difficile (does not cross into the GI tract)
- Infusion reaction/red man syndrome from too rapid of an infusion rate; do not infuse faster than 1 gram per hour
209
What are some side effects associated with Vancomycin?
Abdominal pain, nausea (oral route), phlebitis (irritation to vein), myelosuppression (neutropenia/thrombocytopenia), drug fever, severe skin reactions (SJS/TEN)
210
What are some monitoring parameters of Vancomycin?
- Renal function, drug levels, WBC
- AUC/MIIC ratio (improved outcomes and less toxicity) or steady state trough (drawn 30 minutes before the 4th or 5th dose)
- Serious MRSA infections: AUC/MIC ratio of 400-600 recommended or goal trough 15-20 mcg/mL
- Other infections: goal trough 10-15 mcg/mL
211
What are some key drug interactions of Vancomycin?
- The risk of nephrotoxicity is increased when used with other nephrotoxic drugs
- Vancomycin can increase the risk of ototoxicity when used with other ototoxic drugs
212
What is the MOA of lipoglycopeptides?
Lipoglycopeptides inhibit bacterial cell wall synthesis by binding to the D-alanyl-D-alanine portion of the cell wall, blocking polymerization and cross-linking of peptidoglycan and disrupting bacterial membrane potential and changing cell permeability. They have concentration-dependent activity against similar pathogens as vancomycin
213
What are some examples of lipoglycopeptides?
Telavancin (Vibativ), Oritavancin (Orbactiv), Dalbavancin (Dalvance)
214
What are some boxed warnings of Telavancin?
- Fetal risk: obtain pregnancy test prior to starting therapy (nephrotoxicity)
- Increased mortality with pre-existing moderate-to-severe renal impairment (CrCl < 50 mL/min) when compared to vancomycin in pneumonia trials
215
What are some contraindications of Telavancin?
Concurrent use of IV unfractionated heparin (UFH)
216
What are some warnings associated with Telavancin?
Can falsely increase coagulation tests, but does not increase bleeding risk; red man syndrome with rapid IV administration (give over > 60 minutes); QT prolongation
217
What are some side effects of Telavancin?
Metallic taste, N/V, increased SCr, foamy urine
218
What are some monitoring parameters of Telavancin?
Renal function, pregnancy status
219
What are some contraindications of Oritavancin?
Do not use IV UFH for 120 hours (5 days) after oritavancin administration due to interference (false elevations) with aPTT laboratory results
220
What are some warnings of Oritavancin and Dalbavancin?
- Can cause falsely increase PT/INR for up to 12 hours and aPTT for up to 120 hours after a dose
- Oritavancin: use a different antibiotic if osteomyelitis is confirmed or suspected
- Dalbavancin: increased ALT > 3x the upper limit of normal
221
What are some side effects of Oritavancin and Dalbavancin?
Infusion reaction (red man syndrome), N/V/D, headache, rash
222
What are some monitoring parameters of Oritavancin and Dalbavancin?
Signs of osteomyelitis (oritavancin), LFTs, renal function
223
What are some notes about Oritavancin and Dalbavancin?
Extremely long half-life allows a single-dose regimen for both
224
What are some key Telavancin/Oritavancin drug interactions?
- Avoid telavancin in patients with congenital long QT syndrome, known QT prolongation or uncompensated heart failure. Use caution with other medications known to prolong the QT interval
- Oritavancin is a weak inhibitor of CYP2C9 and CYP2C19, and a weak inducer of CYP3A4 and CYP2D6. Use caution when coadministered with drugs metabolized by these enzymes (including warfarin)
225
What is the MOA of Daptomycin?
Daptomycin is a cyclic lipopeptide that binds to cell membrane components, causing rapid depolarization which inhibits all intracellular replication processes, including protein synthesis, and causes cell death
226
Describe the spectrum of activity of Daptomycin
Daptomycin has concentration-dependent activity against most gram-positive bacteria, including Staphylococci (MRSA) and Enterococci (both species of VRE, E. faecium and E. faecalis). It has no activity against gram-negative pathoggens
227
What can't Daptomycin be used to treat pneumonia?
Drug is inactivated in the lungs by surfactant
228
What are some warnings associated with Daptomycin?
- Myopathy and rhabdomyolysis: discontinue in patients with s/sx and CPK > 1000 units/L (5x ULN), or in asymptomatic patients with a CPK > 2000 units/L (10x ULN); consider temporarily withholding other drugs that can cause muscle damage (e.g. statins) 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
229
What are some side effects of Daptomycin?
Increased CPK, abdominal pain, pruritus, chest pain, edema, hypertension, acute kidney injury
230
What are some monitoring parameters of Daptomycin?
CPK level weekly (more frequently if on a statin or with renal impairment); muscle pain/weakness, s/sx of neuropathy, dyspnea
231
What are some notes associated with Daptomycin?
- Cubicin: compatible with NS and LR (no dextrose)
- Cubicin RF: compatible with NS (no dextrose) but must use only sterile or bacteriostatic water for injection to reconstitute the lyophilized powder (before diluting further with NS)
232
What are some significant daptomycin drug interactions?
Daptomycin can have additive risk of muscle toxicity when used in conjunction with statins
233
What is the MOA of Oxazolidinones?
They bind to the 50S subunit of the bacterial ribosome, inhibiting translation and protein synthesis. They have activity against similar pathogens as vancomycin, but also cover VRE (E. faecium and E. faecalis)
234
What are some examples of Oxazolidinones?
Linezolid and Tedizolid
235
What is a contraindication of Linezolid?
Do not use with or within 2 weeks of MAO inhibitors
236
What are some warnings associated with Linezolid?
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 (caution with insulin or other hypoglycemic drugs), seizures, lactic acidosis, increased BP (caution and monitor BP in patients with uncontrolled hypertension and untreated hyperthyroidism)
237
What are some side effects of Linezolid?
Decreased platelets, decreased Hgb, decreased WBC, HA, nausea, diarrhea, increased LFTs
238
What are some monitoring parameters of Linezolid?
HR, BP, BG (in diabetes), weekly CBC, visual fiunction
239
What are some notes about Linezolid?
Do not shake Linezolid suspension
240
What are some warnings associated with Tedizolid?
Consider alternative treatment in patients with neutropenia
241
What are some side effects associated with Tedizolid?
Nausea, diarrhea, paresthesias, hypertension, visual impairment, blurred vision (less GI side effects and myelosuppression compared to Linezolid)
242
What are some key Linezolid/Tedizolid drug interactions?
- Linezolid and tedizolid are reversible monoamine oxidase inhibitors. Avoid tyramine-containing foods and serotonergic drugs
- Linezolid can exacerbate hypoglycemic episodes; use caution in patients receiving insulin or oral hypoglycemic drugs
243
What is the MOA of Quinupristin/Dalfopristin?
This drug is a streptogramin; it binds to the 50S ribosomal subunit inhibiting protein synthesis
244
Describe the spectrum of activity of Quinupristin/Dalfopristin
It is active against most gram-positive bacteria, including Staphylococci (MRSA) and Enterococcus faecium (VRE, but no E. faecalis
245
What is Quinupristin/Dalfopristin indicated for?
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
246
What are some side effects of Quinupristin/Dalfopristin?
Arthralgias/myalgias (up to 47% of patients), infusion reactions, including edema and pain at infusion site (up to 44% of patients), phlebitis (up to 40% of patients), hyperbilirubinemia (up to 35% of patients), CPK elevations, GI upset, increased LFTs
247
What are some notes about Quinupristin/Dalfopristin?
- Dilute in D5W only
| - Administer via central line, such as a peripherally inserted central catheter (PICC), to avoid phlebitis
248
What are some key drug interactions of Quinupristin/Dalfopristin?
Quinupristin/Dalfopristin is a weak CYP3A4 inhibitor, it can increase levels of CCBs, cyclosporine, dofetilide and others
249
What is the MOA of Tigecycline?
Tigecycline is a glycylcycline. It binds to the 30S ribosomal subunit inhibiting protein synthesis; structurally, it is related to the tetracyclines
250
Describe the spectrum of activity of Tigecycline
Tigecycline has broad-spectrum 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 Ps:" Pseudomonas, Proteus, Providencia species
251
What are the indications for Tigecycline?
Tigecycline is approved for complicated skin and soft-tissue infections, intra-abdominal infections and community-acquired pneumonia; use is limited
252
What is a boxed warning of Tigecycline?
Increased risk of death, use only when alternative treatments are not suitable
253
What are some warnings associated with Tigecycline?
- Hepatotoxicity, pancreatitis, photosensitivity, teeth discoloration in children < 8 years old (avoid use)
- Lower cure rates in ventilator-associated pneumonia
254
What are some side effects associated with Tigecycline?
N/V (can be intractable), diarrhea, headache, dizziness, increased LFT, rash/severe skin reactions (SJS)
255
What are some notes about Tigecycline?
- Do not use for bloodstream infections; it does not achieve adequate concentrations in the blood since it is lipophilic (drug distributes quickly out of the blood into tissues)
- Reconstituted solution should be yellow-orange; discard if not this color
256
What are some key Tigecycline drug interactions?
Tigecycline can increase the INR in patients taking warfarin
257
What are the two drugs in the Polymyxin class?
Colistimethate (sometimes referred to as colistin) and polymxin B
258
What is the MOA of Colistimethate?
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
259
Describe the spectrum of activity of Polymyxins
Polymyxins have activity against gram-negative bacteria, such as Enterobacter spp., E. coli, Klebsiella pneumoniae and Pseudomonas aeruginosa (but not Proteus spp.)
260
When are Polymyxins typically used?
Due to the risk of toxicities, they are used primarily for MDR gram-negative pathogens in combination with other antibiotics
261
What are some warnings associated with colistimethate?
Dose-dependent nephrotoxicity (monitor renal function and electrolytes), neurotoxicity (dizziness, headache, tingling, oral paresthesia, vertigo)
262
What are some notes associated with Colistimethate?
- Colistimethate is a prodrug that is converted to colistin (the active form); assess dose carefully, as it can be represented in units of colistimethate, mg of colistimethate or mg of colistin base activity
- Avoid use with other nephrotoxic medications
- Neurotoxicity can result in respiratory paralysis from neuromuscular blockade
263
What are some boxed warnings of Polymyxin B?
- Nephrotoxicity (dose-dependent)
- Neurotoxicity (dizziness, tingling, numbness, paresthesia, vertigo
- Should only be administered to hospitalized patients
- Avoid concurrent or sequential use of other neurotoxic or nephrotoxic drugs
- Neurotoxicity can result in respiratory paralysis from neuromuscular blockade
264
What is a monitoring parameter of Polymyxin B?
Renal function
265
What are some notes about Polymyxin B?
1 mg = 10,000 units polymyxin B
266
What are some key polymyxin drug interactions?
Other nephrotoxic drugs can enhance the nephrotoxic effects
267
What is the MOA of Chloramphenicol?
Chloramphenicol reversibly binds to the 50S subunit of the bacterial ribosome, inhibiting protein synthesis
268
Describe the spectrum of activity of Chloramphenicol
It has activity against gram-positive, gram-negative, anaerobes and atypical organisms
269
What is the boxed warning of Chloramphenicol?
Serious and fatal blood dyscrasias (aplastic anemia, pancytopenia - may be irreversible)
270
What are some warnings associated with Chloramphenicol?
Gray syndrome with high serum levels: circulatory collapse, cyanosis, acidosis, abdominal distention, myocardial depression, coma and death
271
What are some monitoring parameters of Chloramphenicol?
CBC at baseline and every 2 days during therapy, LFTs, renal function, serum drug concentrations
272
What is the MOA of Clindamycin?
Clindamycin is a lincosamide that reversibly binds to the 50S subunit of the bacterial ribosome, inhibiting protein synthesis
273
Describe the spectrum of activity of Clindamycin
It has activity against most gram-positive bacteria (including some CA-MRSA) and anaerobes. It does not cover Enterococcus or Gram-negative pathogens and has limited to no gram-negative anaerobic activity
274
What is a boxed warning of Clindamycin?
Colitis (C. difficile)
275
What are some warnings associated with Clindamycin?
Severe or fatal skin reactions (SJS/TEN/DRESS)
276
What are some side effects of Clindamycin?
N/V/D, rash, urticaria, increased LFTs (rare)
277
What are some notes associated with Clindamycin?
- An induction test (D-test) should be performed on S. aureus that is susceptible to clindamycin but resistant to erythromycin; a flattened zone between the disks (positive D-test) indicates inducible clindamycin resistance and clindamycin should not be used
- Common uses: purulent and non-purulent skin infections, beta-lactam alternative for dental abscesses
278
What is the MOA of Metronidazole and related drugs?
These antibiotics cause a loss of helical DNA structure and strand breakage resulting in inhibiting of protein synthesis
279
Describe the spectrum of activity of Metronidazole
Metronidazole has activity against anaerobes and protozoal infections
280
What is Metronidazole used for?
It is effective for bacterial vaginosis, tricomoniasis, giardiasis, amebiasis, C. difficile (though not preferred) and is used in combination regimens for intra-abdominal infections
281
What is Tinidazole used for?
Tinidazole is structurally related to metronidazole, but activity is limited to protozoa (giardiasis, amebiasis), trichomoniasis and bacterial vaginosis organisms
282
What is the only indication of Secnidazole?
Bacterial vaginosis
283
What is a boxed warning of Metronidazole and Tinidazole?
Possibly carcinogenic based on animal data
284
What are some contraindications of Metronidazole and Tinidazole?
- Pregnancy (1st trimester), use of alcohol or propylene glycol-containing products during treatment or within 3 days of treatment discontinuation (disulfiram reaction)
- Metronidazole: use of disulfiram within the past 2 weeks
- Tinidazole: breastfeeding
285
What are some warnings associated with Metronidazole and Tinidazole?
- CNS effects: seizures, peripheral neuropathy
| - Metronidazole: aseptic meningitis, encephalopathy, optic neuropathy
286
What are some side effects of Metronidazole and Tinidazole?
Metallic taste, HA, nausea, furry tongue, darkened urine, dizziness, rash/severe skin reactions (SJS/TEN)
287
What are some warnings of Secnidazole?
Possibly carcinogenic (based on animal data with structurally similar drugs)
288
What are some side effects of Secnidazole?
Vulvovaginal candidiasis, HA, N/D
289
What are some key Metronidazole and Tinidazole drug interactions?
- Metronidazole and Tinidazole should not be used with alcohol (during and for 3 days after discontinuation of treatment) due to a potential disulfiram-like reaction (abdominal cramping, nausea/vomiting, headaches and flushing)
- Metronidazole is a weak inhibitor of CYP2C9 and can cause an increased INR in patients taking warfarin
290
What is the MOA of Lefamulin?
Lefamulin is a first in-class pleuromutilin. It inhibits bacterial protein synthesis by binding to the peptidyl transferase center of the 50S ribosomal subunit
291
What are some contraindications of Lefamulin?
Use with CYP3A4 substrates that prolong the QT interval
292
What are some warnings associated with Lefamulin?
Avoid in pregnancy (teratogenic), QT prolongation, C. difficile-associated diarrhea
293
What are some side effects associated with Lefamulin?
Diarrhea, nausea, infection site reactions
294
What are some notes associated with Lefamulin?
Approved for CAP
295
What is the MOA of Fidaxomicin?
Fidaxomicin inhibits RNA polymerase, resulting in inhibition of protein synthesis and cell death. It is used for C. difficile infections
296
What are some warnings about Fidaxomicin?
Not effective for systemic infections: absorption is minimal
297
What are some side effects of Fidaxomicin?
N/V, abdominal pain, GI bleeding, anemia
298
What is the MOA of Rifaximin?
Rifaximin inhibits bacterial RNA synthesis by binding to bacterial DNA-dependent RNA polymerase. It is structurally related to rifampin
299
What are some side effects of Rifaximin?
Peripheral edema, dizziness, headache, flatulence, nausea, abdominal pain, rash/pruritus
300
What are some notes associated with Rifaximin?
- Not effective for systemic infections (< 1% absorption)
| - Used off-label for C. difficile infection (second or subsequent recurrence) and treatment of hepatic encephalopathy
301
What is the MOA of fosfomycin?
Inhibits bacterial cell wall synthesis by inactivating the enzyme pyruval transferase, which is critical in the synthesis of cell walls
302
Describe the spectrum of activity of Fosfomycin?
It has activity against E. coli (including ESBLs) and E. faecalis (including VRE). A single dose regimen is used for uncomplicated UTI (cystitis only)
303
What are some side effects of Fosfomycin?
Headache, diarrhea, nausea
304
What are some notes of Fosfomycin?
Concentrates in the urine
305
What is the MOA of Nitrofurantoin?
Nitrofurantoin is a bacterial cell wall inhibitor.
306
Describe the spectrum of activity of Nitrofurantoin
It is used for uncomplicated UTI (cystitis only). It covers E. coli, Klebsiella, Enterobacter, S. aureus and Enterococcus (VRE)
307
What are some contraindications of Nitrofurantoin?
Renal impairment (CrCl < 60 mL/min): inadequate urine concentrations and risk for accumulation of neurotoxins; previous history of cholestatic jaundice/hepatic dysfunction; pregnancy (at term)
308
What are some warnings associated with Nitrofurantoin?
Optic neuritis, hepatotoxicity, peripheral neuropathy, pulmonary toxicity, hemolytic anemia (use caution in patients with G6PD deficiency)
309
What are some side effects of Nitrofurantoin?
GI upset (take with food), headache, rash, brown urine discoloration (harmless)
310
What are some notes about Nitrofurantoin?
Concentrates in the urine
311
What is Mupirocin used for?
Mupirocin is a topical antimicrobial ointment used to eliminate Staphylococci (MRSA) colonization of the nares
312
What are some side effects of Mupirocin?
Headache, burning, localized irritation, rhinitis, pharyngitis
313
Which antibiotics are commonly used for methicillin-sensitive Staphylococcus aureus (MSSA)?
- Dicloxacillin, nafcillin, oxacillin
- Cefazolin, cephalexin (and other 1st and 2nd generation cephalosporins)
- Amoxillin/clavulanate, ampicillin/sulbactam
- Doxycycline, minocycline
- SMX/TMP
314
Which antibiotics are commonly used for community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) skin & soft tissue infections (SSTIs)?
SMX/TMP, Doxycycline, Minocycline, Clindamycin, Linezolid
315
Which antibiotics are commonly used for severe SSTIs requiring IV treatment or hospitalization (cover MRSA and Streptococci)?
Vancomycin (consider using alternative if MIC > 2), Linezolid, tedizolid, Daptomycin, Ceftaroline, Telavancin, Oritavancin, Dalbavancin, Quinupristin/Dalfopristin, Tigecycline
316
Which antibiotics are commonly used for nosocomial MRSA?
Vancomycin (consider using alternative if MIC > 2), Linezolid, Daptomycin (not in pneumonia), Telavancin
317
Which antibiotics are commonly used for VRE (E. faecalis)?
- Pen G or ampicillin, Linezolid, Daptomycin, Tigecycline
| - Cystitis only: nitrofurantoin, fosfomycin, doxycycline
318
Which antibiotics are commonly used for HNPEK?
Beta-lactam/beta-lactamase inhibitor, amoxicillin (if beta-lactamase negative), cephalosporins (except 1st generation), carbapenems, SM/TMP, aminoglycosides, quinolones
319
Which antibiotics are commonly used for atypical organisms?
Azithromycin, clarithromycin, doxycycline, minocycline, quinolones
320
Which antibiotics are commonly used for Pseudomonas aeruginosa?
Piperacillin/tazobactam, Cefepime, Ceftazidime, Ceftazidime/avibactam, Ceftolozane/tazobactam, carbapenems (except ertapenem), Ciprofloxacin, levofloxacin, Aztreonam, Aminoglycosides, Colistimethate, polymyxin B
321
Which antibiotics are commonly used for Acinetobacter baumannii?
Carbapenems (except ertapenem), Ampicillin/sulbactam, Minocycline, Tigecycline, Quinolones, SMX/TMP, Amikacin, colistimethate, polymyxin B
322
Which antibiotics are commonly used for extended-spectrum beta-lactamase producing gram-negative rose (ESBL GNR) - E. coli, K. pneumoniae, P. mirabilis?
- Carbapenems, Ceftazidime/avibactam, Ceftolozane/tazobactam, aminoglycosides
- Cystitis only: fosfomycin
323
Which antibiotics are commonly used for carbapenem-resistant gram-negative rods (CRE)?
Ceftazidime/avibactam, colistimethate, polymyxin B, meropenem/vaborbactam, imipenem/cilastatin/relebactam
324
Which antibiotics are commonly used for bactreroides fragilis?
Metronidazole, beta-lactam/beta-lactamase inhibitor, Cefotetan., Cefoxitin, Carbaopenems, Tigecycline, others (reduced activity): moxifloxacin
325
Which antibiotics are commonly used for C. difficile infection?
Vancomycin (oral), Fidaxomicin, Metronidazole
326
Which liquid oral antibiotics require refrigeration after reconstitution?
Penicillin VK. Ampicillin, Augmentin, Cephalexin, Cefadroxil, Cefpodoxime, Cefprozil, Cefuroxime, Cefaclor, Ceftibuten, Vancomycin (oral), Valganciclovir
*Amoxicllin: improves taste
327
Which liquid oral antibiotics should not be refrigerated?
Cefdinir, Azithromycin, Clarithromycin, Doxycycline, Cipro, Levofloxacin, Clindamycin, Linezolid, Bactrim, Acyclovir, Fluconazole, Posaconazole, Voriconazole, Nystatin
328
Which IV antibiotics should not be refrigerated?
Metronidazole, Moxifloxacin, Bactrim, Acyclovir
329
Which key drugs do not require renal dose adjustment?
Antistaphylococcal penicillins, Ceftriaxone, Clindamycin, Doxycycline, Macrolides (azithromycin and erythromycin only), Metronidazole, Moxifloxacin, Linezolid
330
Which antibiotics should be taken on an empty stomach?
Ampicillin oral capsules and suspension, ceftibuten suspension, levofloxacin oral solution, penicillin VK, rifampin, isoniazid, itraconazole solution, voriconazole
331
What antibiotic should be taken within one hour of finishing a meal?
Amoxicillin ER
332
Which antibiotics have a 1:1 IV to oral dosing?
Levofloxacin, moxifloxacin, doxycycline, minocycline, linezolid, tedizolid, Metronidazole, Bactrim, Fluconazole, Isavuconazonium, posaconazole, voriconazole
333
What antibiotics should have light protection during administration?
Doxycycline, Micafungin, Pentamidine
334
Which IV antibiotics are compatible with dextrose only?
Quinupristin/Dalfopristin, Bactrim, Amphotericin B, Dalbavancin, oritavancin, Pentamidine
335
Which IV antibiotics are compatible with saline only?
Ampicillin, Ampicillin/Sulbactam, Ertapenem, Daptomycin (Cubicin RF)
336
Which IV antibiotics are compatible with NS/LR only?
Caspofungin, Daptomycin (Cubicin)
337
What are some key counseling points of all antibiotics?
- Proper storage (refrigeration or room temperature) and administration (with or without food) is essential
- Shake suspension 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 rash, nausea, diarrhea (including C. difficile)
338
What are some key counseling points of quinolones?
- Can cause CNS effects (including seizures), hypo/hyperglycemia, peripheral neuropathy, photosensitivity, QT prolongation, tendon inflammation (tendinitis) or tendon rupture (can present with a pop or pain/swelling in the back of the ankle, shoulder or hand)
- Avoid in pregnancy, breastfeeding and children
- Drug interactions due to binding
339
What are some key counseling points of Macrolides?
Can cause GI upset, QT prolongation
340
What are some key counseling points of tetracyclines?
- Avoid in pregnancy, breastfeeding and children < 8 years old
- Drug interactions due to binding
- Can cause photosensitivity
- Doxycycline: take with a full glass of water and remain upright for 30 minutes after the dose to avoid GI irritation
341
What are some key counseling points of Bactrim?
- Avoid in pregnancy or breastfeeding, sulfa allergy
| - Can cause photosensitivity and crystals in the urine (take with a full glass of water)
342
What are some key counseling points of Metronidazole?
- Do not use any alcohol products while using this medication, and for at least three days afterward
- Can cause nausea, metallic taste in the mouth
343
What are some key counseling points of Nitrofurantoin?
- Take with food to decrease nausea
| - Can cause nausea, brown discoloration of urine (temporary and harmless)
344
What are some key counseling points of Mupirocin nasal ointment?
- Place 1/2 the ointment from the tube into one nostril and the other 1/2 into the other nostril. Press the nostrils at the same time and let go; do this as 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
