Infectious Disease I Flashcards
1
Q
Common pathogens of the CNS/Meningitis
A
Group B Streptococcus/E Coli (Young)
Haemophilus influenzae
Listeria (Young/Old)
Neisseria meningitidis
Streptococcus pneumonia
2
Q
Common pathogens of the Mouth
A
Anaerobic GNR (Prevotella)
Peptostreptococcus
Viridans group Streptococci
3
Q
Common pathogens of the Upper respiratory
A
Haemophilus influenzae
Moraxella catarrhalis
Streptococcus pyogenes
Streptococcus pneumonae
4
Q
Common pathogens of the endocarditis (Heart)
A
Enterococci
Staphylococcus aureus (including MRSA)
Staphylococcus epidermidis
Streptococci
5
Q
Common pathogens of the lower respiratory community
A
Atypicals (legionella, Mycoplasma)
Chlamdophilia
Enteric GNR (alcoholics)
Haemophilus influenzae
Streptococcus pneumonia
6
Q
Common pathogens of the lower respiratory hospital
A
Acinetobacter baumannii
Enteric GNR (ESBL, MDR)
Pseudomonas aeruginosa
Streptococcus pneumonia
Staphylococcus aureus (including MRSA)
7
Q
Common pathogens of the Skin and Soft Tissue
A
aerobic/anaerobic GNR (in diabetes)
Pasteurella multocida
Staphylococcus aureus
Staphylococcus epidermidis
Streptococcus pyogenes
8
Q
Common pathogens of the Urinary Tract
A
E-coli
Enterococci
Klebsiella
Proteus
Staphylococcus saprophytic
9
Q
Common pathogens of the Bone and Joint
A
GNR (only in specific situations)
Staphylococcus aureus
Staphylococcus epidermidis
Streptococci
Neisseria gonorhhea
10
Q
Gram positive Cocci (appear purple on stain)
Clusters
A
Staphylococcus spp.
including MRSA, MSSA
11
Q
Gram positive Cocci (appear purple on stain)
Pairs and chains
A
Strep pneumoniae (diplococci)
streptococcus spp.
enterococcus spp.
12
Q
Gram positive Rods (appear purple on stain)
A
Listeria
monocytogenes
Corynebacterium spp
13
Q
Gram positive Anaerobes (appear purple on stain)
A
peptosterptococcus
propionibacterium ances
clostridioides
14
Q
Atypicals (do not stain well)
A
Chlamydia
Legionella
Mycoplasma pneumoniae
Mycobacterium tuberculosis
15
Q
Gram Negative (appear pink on stain)
Cocci
A
Neisseria
16
Q
Gram Negative (appear pink on stain)
Rods
Colonize in Gut
A
Proteus mirbillis
E-Coli
Klebsiella spp
Serratia spp.
Enterobacter clocae
Citrobacter spp.
17
Q
Gram Negative (appear pink on stain)
Rods
Do not colonize in Gut
A
Pseudomonas aeruginosa
Haemophilus influenzae
Providencia spp
18
Q
Gram Negative (appear pink on stain)
Coccobacilli
A
Acinetobacter bumannii
Bordetella pertussis
Moraxella catarrhalis
19
Q
Gram Negative (appear pink on stain)
curved or spiral shaped
A
H. Pylori
Campylobacter
Borrelia
Treponema
Leptospira spp.
20
Q
Gram Negative (appear pink on stain)
Atypicals
A
Bacteriodes fragilis
Prevotella
21
Q
Antibiogram
A
show susceptibility patterns generally a year
22
Q
EE_PEAKS
Common resistant pathogens
A
Enterococcus faecalis (VRE) Enterococcus Faecium (VRE)
Pseudomonas aeruginosa
E. Coli (ESBL, CRE)
Acinetobacter baumannii
Klebsiella pneumoniae (ESBL, CRE)
Staph aureus (MRSA)
23
Q
Intrinsic resistance
A
resistance that is natural to the organism
24
Q
Selection Pressure
A
resistance occurs when antibiotics kill off susceptible bacteria, leaving behibd more resistant strains to multiply
25
Acquired resistance
bacterial genes are transferred
26
Enzyme activation
enzymes produced by the bacteria break down the antibiotc
27
BBW warning for clindamycin
C-diff
Others can cause but do not have a BBW
highest risk are with broad spectrum;
PCN
Cephalosporins,
quinolones
28
Antimicrobial sterwardship programs
designed to improve patient safety and outcomes, curb resistance, reduce adverse effects and promote cost effectivness
29
Drugs that target bacterial cell wall
Cell wall inhibitors
betalactams:
penicillins
cephalosporins
carbapenems
Monobactam;
aztreonam
vancomycin
dalbavancin
telavancin
oritavancin
30
Drugs that target bacterial cell membrane
Cell membrane inhibitors
Polymixin
Daptomycin
**Telavancin
Oritavancin**
31
Drugs that target bacterial protein synthesis
protein synthesis inhibitors
**50S**
Macrolides
Clindamycin
Linezolid
Quiupristin/dalfopristin
**30S**
Aminoglycosides
Tetracyclines
**23S**
Tedizolid
32
Drugs that target bacterial DNA/RNA synthesis
DNa/RNA inhibitors
Quinolones
topoisomerase
metronidazole
tinidazole
Rifampin
33
Drugs that target bacterial folic acid synthesis
folic acid synthesis inhibitors
sulfonamides
trimethoprim
dapsone
34
Hydrophillic agents
Betalactams
Aminoglycosides
Glycopeptides
Daptomycin
polymixin
35
Lipophillic agents
Quinolones
macrolides
rifampin
linezolid
tetracyclines
36
Concentration dependent
CMax:MIC
Aminoglycosides
quinolones
daptomycin
**GOAL**
High peak, low trough
give large doses for long intervals
37
Exposure dependent
AUC:MIC
Vancomycin
macrolides
tetracyclines
polymixins
**GOAL**
exposure over time
strategy is variable
38
Time dependent
Time\>MIC
Beta-lactams
**GOAL**
Maintain the drug level grater than the mic for most of the dosing interval
strategy is shorter dosing intervals and longer or continuous infusions
39
Natural Penecillins
Penecillin V Potassium (Pen VK)
Penecillin G Benzathine (Bicillin L-A)
40
Antistaphylococcus penecillin
Dicloxacillin
Oxacillin
**Nafcillin (Injection)**
41
Aminopenecillins
Amoxicillin **(Chewable)**
Amoxicillin w/ clavulanate **(Chewable)**
**Ampicillin (Injection)**
**Ampicillin w/ sulbactam (Injection)**
42
Extended spectrum antibiotics
Pipercillin/Tazobactam **(injection)**
## Footnote
**prolonged or extended infusions _each dose is over 4 hours_**
43
Penecillin class safety/side effects/monitoring
**BBW** - Pen G is not for IV use it is IM
**Contraindications**
Augmentin and unasyn: history of jaundice
**Side effects**
seizures with accumulation, GI upset, diarrhea, rash (SJS/TEN)
**Monitor**
Renal function
44
Penecillin Notes
Antistaphylococcal Penicillins
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_
45
Penecillin drug interaction
Probenecid can increase the levels of betalactams by interfering with renal excretion
46
All penicillins should be avoided in patients with a beta-lactam allergy
Exceptions: treatment of _syphilis during pregnancy_ (all patients) and in **_HIV patients_** with poor compliance/follow-up desensitize and treat with **_penicillin G benzathine_**
47
All penicillins increase the risk of seizures if accumulation occurs (e.g., failure to dose adjust in renal dysfunction)
All penicillins increase the risk of seizures if accumulation occurs (e.g., failure to dose adjust in renal dysfunction)
48
A first-line treatment for strep throat and mild nonpurulent skin infections (no abscess)
Penicillin VK
49
First-line treatment for acute otitis media (pediatric dose: 80-90 mg/kg/day)
Drug of choice for infective endocarditis prophylaxis before dental procedures (2 grams PO x 1, 30-60 minutes before procedure)
Amoxicillin
50
First-line treatment for acute otitis media (pediatric dose: 90 mg/kg/day) and for sinus infections (if antibiotics indicated)
Use the lowest dose of clavulanate to diarrhea
Amoxicillin/Clavulanate (Augmentin)
51
Covers MSSA only (no MRSA)
No renal dose adjustment needed
Dicloxacillin
52
■ Drug of choice for syphilis (2.4 million units IM x 1)
■ Not for IV use; can cause death
Penicillin G Benzathine (Bicillin L-A)
53
■ Only penicillin active against Pseudomonas
☐ Extended infusions (4 hours) can be used to maximize T \> MIC
Piperacillin/Tazobactam (Zosyn)
54
CEPHALOSPORINS
Generally, the Gram-negative spectrum increases with each generation. As a class, **_they are not active against Enterococcus spp. or atypical organisms._**
55
First generation: CEPHALOSPORINS
excellent activity against **_Gram-positive cocci_** (e.g., Streptococci and Staphylococci) and p_referred 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.
56
CEPHALOSPORINS: Second generation:
There are two types.
Drugs such as cefuroxime cover Staphylococci, more resistant strains of S. pneumoniae plus **_Haemophilus, Neisseria, Proteus, E. coli and Klebsiella (HNPEK)_**.
The second type, _**cefotetan and cefoxitin**, have added coverage of **Gram-negative anaerobes (B. fragilis)**_**.**
57
CEPHALOSPORINS: Third generation: there are two groups.
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._**
58
CEPHALOSPORINS: Fourth generation:
**only includes cefepime**, which has **_broad Gram-negative activity_** (HNPEK, CAPES and **Pseudomonas**), and Gram-positive activity similar to ceftriaxone.
59
CEPHALOSPORINS: Fifth generation:
**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._**
60
Other cephalosporins: **Beta-lactamase inhibitor combinations:**
_ceftazidime/avibactam_ and c_eftolozane/tazobactam_ have a similar spectrum as ceftazidime but with added _activity against **MDR Pseudomonas** and other **MDR Gram-negative rods**._
61
1st Generation Cephalosporin
CEfazolin (Ancef)
_Cephalexin (Keflex) P**O 250-500mg Q6-12H**_
62
2nd Generation Cephalosporin
Cefuroxime (Ceftin)
Cefotetan (Cefotan)
63
3rd Generation Cephalosporin
**Group 1**
Cefdinir (Omnicef)
CEftriaxone (Rocephin)
Cefotaxime
**Group 2**
Ceftazidime (Fortaz)
64
4th Generation Cephalosporin
Cefepime
65
5th Generation Cephalosporin
Ceftaroline
66
CONTRAINDICATIONS (CEFTRIAXONE)
Hyperbilirubinemic neonates (causes biliary sludging, kernicterus)
Concurrent use with calcium-containing IV products in neonates ≤28 days old
67
WARNINGS Cefotetan
Cefotetan contains a side chain [N-methylthiotetrazole (NMTT or 1-MTT)] which can ↑ the risk of **_bleeding_** and cause a **_disulfiram-like reaction with alcohol ingestion_**
68
Cephalosporin - CLASS EFFECTS ■
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) 30 1827
Risk of seizures if accumulation occurs (e.g., failure to dose adjust in renal dysfunction)
69
1st Generation: Cephalexin (Keflex)
■ Common uses: skin infections (MSSA), strep throat
70
2nd Generation: Cefuroxime (Ceftin)
■ Common uses: acute otitis media, community-acquired pneumonia (CAP), sinus infection (if antibiotics indicated)
71
3rd Generation: Cefdinir (Omnicef)
Common uses: CAP, sinus infection (if antibiotics indicated)
72
1st Generation: Cefazolin (Ancef)
Common use: surgical prophylaxis
73
2nd Generation: Cefotetan (Cefotan) and Cefoxitin
■ Anaerobic coverage (B. fragilis)
■ Common use: surgical prophylaxis (colorectal procedures)
Cefotetan can cause a disulfiram-like reaction with alcohol ingestion
74
3rd Generation: 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)
75
Ceftazidime (3rd Generation) and Cefepime (4th Generation)
Active against Pseudomonas
76
Ceftolozane/Tazobactam and Ceftazidime/Avibactam
Used for MDR Gram-negative organisms (including Pseudomonas)
77
Ceftaroline
Only beta-lactam active against MRSA
Common uses: CAP, skin and soft tissue infections
78
Carbapenems
Very broad spectrum
**_Reserved for MDR gram negative_**
Active against Gram negative, Gram Positive i**_ncluding ESBL_**
**_NO COVERAGE of atypicals, MRSA, VRE_**
79
Ertapenem
**_Is different_** from other carnbapenems it has **_NO ACTIVITY against pseudomonas, acinetobacter or enterococcus_**
STABLE ONLY IN NS
80
Ertapenam does not cover?
Pseudomonas
Acinetobacter
Enterococcus
81
Meropenam (Merem)
Warnings
**_Do not use in patients with PCN allergy_** small risk of cross reactivity.
CNS adverse effects, including states of confusion and **_seizures_**.
Monitoring
**_renal functions_**
Side effects
DRESS
82
Key features of carbapenems
Class effects
All active against ESBL-producing organism and pseudomonas (ertapenem does not cover pseudomonas)
Do not use with penecillin
Seizure risk (with higher doses, failure to dose adjust in renal dysfunction, or use od imipenem/cilistatin)
83
Key features of carbapenems
What are **_NOT_** covered
Atypicals
VRE
MRSA
C-Diff
Stenotropomonas
**_E_**rt**_AP_**enem - (Enterococcus, Acinetobacter, Pseudomonas)
84
Key features of carbapenems
**_COMMON_** uses
Polymicrobial infections (Sever diabetic infections)
Empiric therapy when resistant organisms suspected
**_ESBL- positive infections_**
Ressitant pseudomonas or acinetobacter infections **_(Except ertapenem)_**
85
Are carbapenems braod or narrow spectrum?
Very broad
86
Key features of carbapenems
mixed with 0.9%
All are IV only, Ertapenem MUST be diluted in normal saline (0.9%)
87
Aztreonam (monobactam) inhibits cell wall synthesis by binding to penecillin binding protein (PBP)
Cross reactivity with beta-lactam highly unlikely. Aztreonam is primarily used when a **_beta lactam allergy is present_**
88
Aztreonam covers what bugs?
MANY gram negative bacteria, including pseudomonas.
It has **_NO GRAM-positive or anaerobic avtivity_**
89
Beta-lactam spectrum of activty
Which beta-lactams cover MRSA?
**_Ceftaroline_**
90
Beta-lactam spectrum of activty
Which beta-lactams cover MSSA?
Oxacillin, Nafcillin
Amox/Clav, Ampicillin/Sulbactam, Piper/Tazo
Cefazolin (1st), Cephalexin (1st)
Cefuroxime (2nd), Cefotetan (2nd), Cefoxitin (2nd)
Cefotaxime (3rd), Ceftriaxone (3rd)
Cefepime (4th)
Ceftaroline (5th)
Ceftazidime/Avibactam, Ceftolozane/Tazobactam
Imipenem/Cilistatin, Meropenam, Doripenam
Ertapenem
91
Aminoglycosides -
Coverage
_**Gram-negative, including pseudomonas
Synergy for Gram-positives (staphylococcus/enterococci)**_
92
Aminoglycosides -
Dosing (gentamicin/tobramycin/amikacin)
If underweight use TBW, if obese use AdjBW
**_Traditional (1-2.5 mg/kg IV Q8H) - Peaks and troughs_**
CrCl \>60 Q8
Extended-interval: (4-7 mg/kg IV Q24H) - draw a random level and use nomogram
93
Aminoglycosides use two dosing strategies, whart are they?
Traditional: uses lower doses more frequently
Extended interval dosing: less accumulation, less toxicity and decreased cost
94
Aminoglycosides -
Good News
Kill Gram-Negatives, synergistic with beta-lactams for gram-positive infections low resistance and cost
95
Aminoglycosides -
Bad News
Toxicities: renal damage and ototoxicities
96
Aminoglycosides -
Smart Idea/Dosing
Concentration-dependent killing --\> give larger doses less frequently (extended-interval dosing) --\> allow kidneys to recover
97
Aminoglycoside BBW
Nephrotoxicity
Ototoxicity
Neuromuscular blockade
AVOID with neurotoxic/nephrotoxic drugs
98
Aminoglycoside warnings
Use **_caution in renal imparimen_**t, also in elderly and those taking other nephrotoxic drugs (a**_mphotericin B, cisplatin, polymixin, cyclosporin, loop diuretics, NSAIDS, radiocontrast dye, tacrolimus and vancomycin)_**
99
_Peaks and Trough_
Gentamicin gram positive infection (synergy)
Gentamicin gram negative infection
Tobramycin
Amikacin
Gent (GP) - Peak 3-4mcg/mL \<\> Trough \<1mcg/mL
Gent (GN)- Peak 5-10mcg/mL \<\> Trough **_\< 2mcg/mL_**
Tobramycin - Peak 5-10mcg/mL \<\> Trough **_\< 2mcg/mL_**
Amikacin - - Peak 20-30mcg/mL \<\> Trough \< 5mcg/mL
100
Quinolones -
Concentration-dependent killing
101
Quinolones -
Boxed Warnings
Tendon inflammation or rupture
peripheral neuropathy
CNS effects (seizures)
Use-last line (only if no alternatives)
102
Quinolones -
Warnings
QT prolongation (higher risk with moxi)
Hypo and hyperglycemia
Psychiatric disturbances - delirium, agitation, memory determent
Photosensitivity
Avoid systemic quinolone use in children and in prgnancy/breastfeeding (exception for anthrax)
103
Quinolones -
Interactions
Chelation with divalent cations
104
Quinolones -
Respiratory Quinolones
Enhanced activity against S. pneumoniae and atypicals
(My Good Lungs)
* *Moxifloxacin** (IV:PO = 1:1, **_NOT renally adjusted so do NOT use for UTIs_**)
* *G**emifloxacin
* *L**evofloxacin
105
Quinolones -
Antispeudomonal quinolone
Levofloxacin **_(IV:PO = 1:1)_**
Ciprofloxacin
**_Enhanced Gram Negative activity -_** Including pneumonia
106
Quinolones -
Profile Review Tips
Caution in patients with CVD, decreased K/Mg, use of other QT prolongating drugs
Avoid if seizure history or using anti epileptic
Avoid in children
Watch for tendon rupture, neuropathy, CNS/psychiatric side effects
107
Qinolones MOA
Inhibit topoisomerase IV and DNA gyrase
108
Quinolones and activity against MRSA?
Delafloxacin - ONLY quinolone recommended for MRSA treatment, all others should be avoided due to high rates of resistance.
109
Moxifloxacin spectrum of activity?
Enhanced gram positive and anaerobic
110
Ciprofloxacin Brand
Cipro
with dexamethasone (Ciprodex)
IV:PO is **_NOT_** 1:1
111
Levofloxacin Brand
Levaquin
112
**_Moxifloxacin_** Brand
Avelox
No renal dose adjustments required
Moxifloxacin **_SHOULD NOT_** be used for **_UTI_**
113
Ciprofloxacin oral suspension counseling points
Shake vigorously for 15 seconds. DO NOT put in NG or other feeding tube
114
Quinolone DDI's
Lanthanum (Fosrenol) sevelmer (Renvela) can decrease serum concentrations for oral quinolones seperate administration by at least 2 hours
CIPRO is a **_STRONG CYP1A2_** inhibitor weak inhbitor of 3A4 and P-GP.
Can increase levels of caffeine, theophylline and tizanidine
115
Quinolone common use anf counseling
Can very by agent:pneumonias, UTI's intra-abdominal infections, travelers diarrhea
AVOID sun exposure, separate from cations, monitor BG, watch for tendon rupture, neuropathy, CNS or psychiatric side effects
116
Macrolides -
Agents in Class
Azithromycin (Zithromax)
Clarithromycin (Biaxin)
Erythromycin (E.E.S)
117
Macrolides - MOA
Azithromycin (Zithromax)
Clarithromycin (Biaxin)
Erythromycin (EES, Ery-Tab, Erythrocin)
Bind to 50s ribosomal sub-unit results in inhibition of RNA-dependent protein synthesis
118
Macrolide spectrum of activity
EXCELLENT activity agains Atypicals
LCMM
Legionella
Chlamydia
Mycoplasma
Mycobacterium
Macrolides are treatment options for CAP (Upper & Lower) and certain STI's (chlamydia & Gonorrhea)
119
Z-Pak vs Tri-Pak
Z-Pak:
500mg day 1 and 250 days 2-5
Tri-Pak:
500mg for 3 days
120
Macrolides -
Safety Issues
**_QT prolongation:_** caution with CVD, decreased K/Mg, use other QT-prolongating drugs
Drug Interactions: clarithromycin/erythromycin **_contraindicated with simvastatin/lovastatin_**
**_Hepatotoxicity_**
**_GI Upset_**
121
Erythromycin and Clarithromycin DDI's
CYP3A4 major substrates and **_CYP3A4 inhibitors_**
Caution with warfarin use
122
Macrolides -
Common Uses
CAP, strep throat
Azithromycin: COPD exacerbations, chlamydia, gonorrhea, MAC prophylaxis
Clarithromycin: H. pylori
Erythromycin: increase gastric motility (patients with gastroparesis)
123
KEY FEATURES OF MACROLIDES
QT Prolongation
Caution with CVD, J- K/Mg and other QT-prolonging drugs (e.g.,
azole antifungals, antipsychotics, methadone, quinolones)
124
KEY FEATURES OF MACROLIDES
Drug Interactions
■ Clarithromycin and erythromycin are strong CYP3A4 inhibitors;
lovastatin and simvastatin are contraindicated ( increase risk of muscle toxicity)
125
TETRACYCLINES
Doxycycline (Vibramycin)
Minocycline (Minocin, Solodyn)
126
TETRACYCLINES MOA?
Inhibit bacterial protein synthesis by reversibly binding to the **_30S_** ribosomal subunit
127
What Gram positive bacteria do macrolides cover?
(Staphylococci, Streptococci, Enterococci, Propionibacterium spp.)
128
What Gram-negative bacteria do macrolides cover, including respiratory flora
(Haemophilus, Moraxella, atypicals)
129
What other unique pathogens do macrolides cover
(e.g., Rickettsiae, Bacillus anthracis. Treponema pallidum and other spirochetes).
130
Which macrolide has broader indications than the other tetracyclines, including respiratory tract infections (e.g., CAP), **_tickborne/rickettsial diseases_**, spirochetes and sexually transmitted infections **_(chlamydia and gonorrhea)._**
**_Doxycycline_**
131
Which macrolide is an option for the treatment of mild skin infections caused by **_CA-MRSA and VRE_** urinary tract infections.
**_Doxycycline_**
132
Which macrolide is often preferred for acne.
**_Minocycline_**
133
Doxycycline brand
**_Vibramycin_**
134
Minocycline Brand
**_Minocin, Solodyn_**
135
No renal dose adjustments required for which macrolide?
Doxycycline
136
Mactolide warnings
**_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
***_Minocycline_***: drug-induced lupus erythematosus ***_(DILE)_***
137
Mactolide NOTES
**_IV:PO ratio is 1:1_** (doxycycline, minocycline)
Tablets and capsules should be taken with 8 oz o f water; with **_doxycycline, sit upright for at least 30 minutes a fter dose_** to avoid esophageal irritation
138
Key features of tetracyclines
Common Uses
* **Doxycycline and minocycline:** ***CA-MRSA skin infections, acne***
* **Doxycycline**: ***first-line*** treatment for ***Lyme disease. Rocky Mountain Spotted Fever (tickborne illnesses), CAP, COPD exacerbations, sinusitis (if antibiotic indicated), VRE UTI, chlamydia (as monotherapy), gonorrhea*** (in combination therapy)
* **Tetracycline:** used In **H. pylori** treatment regimens
**Do not use in pregnancy, breastfeeding or children \< 8 years old**
139
Sulfamethoxazole MOA
Sulfamethoxazole (SMX) inhibits dihydrofolic acid formation from para-aminobenzoic acid.
**_Inhibition of the folic acid pathway._**
140
Sulfamethoxazole/trimethoprim has activity against?
Gram-positive bacteria
Staphylococci (including MRSA and CA-MRSA);
S. pneumoniae and Group A
Gram-negative bacteria (broad)
Haemophilus, Proteus, E. coli, Klebsiella, Enterobacter, **_Shigella, Salmonella and Stenotrophomonas_**
141
SMX/TMP is active against what opportunistic pathogens?
Nocardia, **_Pneumocystis, Toxoplasmosis_**
142
SMX/TMP does not have activity against what pathogens?
**_Pseudomonas, Enterococci, atypicals or anaerobes_**
143
Sulfamethoxazole/Trimethoprim (Bactrim,Bactrim DS)
Dose based on the Trimethoprim component
144
Sulfamethoxazole/Trimethoprim
Single Strength (SS) vs Double Strength (DS)
400 mg SMX/80 mg TMP
800 mg SMX/160 mg TMP
**_SMX:TMP ratio of 5:1_**
145
SMX/TMP is a moderate-strong
CYP2C8 and **CYP2C9 inhibitor**
146
SMX/TMP
Common Uses
**CA-MRSA skin infections**
**UTI**
**Pneumocystis pneumonia (PCP)**
147
5:1 Ratio of SMX/TMP (Dose Based on TMP)
**■ Single strength (SS) tablet contains 80 mg TMP**
**■ Double strength (DS) tablet contains 160 mg TMP - usual dose is one tablet BID**
148
SMX/TMP use with Warfarin
INR increase when used with warfarin. Use alternative antibiotic when possible.
149
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)**
* C. difficile **(using the PO route only)**
150
Vancomycin (Vancocin)
First-line treatment for moderate-severe systemic **MRSA infections**
## Footnote
**Consider an alternative drug when MRSA MIC \> 2 mcg/mL**
151
Vanc (Dose based on **total body weight**)
Systemic infections (IV only) IV: **15-20 mg/kg Q8-12H**
C. diffKile infections (PO only)
## Footnote
**PO: 125 QID x 10 days**
152
Vanc Warnings
**Ototoxicity and nephrotoxicity**
PO formulation is used only for C. difficile colitis and enterocolitis, not for systemic infections; **IV formulation is not effective fo r C. difficile**
153
Vanc monitoring
**Renal function, drug levels** (see below), WBC
**AUC/MIC ratio** (improved outcomes and less toxicity) or steady state trough (drawn 30 minutes before the 4th or 5th dose)
**Serious MRSA infections** (e.g., bacteremia, sepsis, endocarditis, pneumonia, osteomyelitis, meningitis): **AUC/MIC ratio of 400-600** recommended or goal trough **15-20 mcg/mL**
154
Vancomycin can increase the risk of ototoxicity when used with other ototoxic drugs
(e.g., **aminoglycosides, cisplatin, loop diuretics**).
155
The risk of nephrotoxicity is increased when used with othernephrotoxic drugs
(e.g., **aminoglycosides, amphotericin B, cisplatin, polymyxins, cyclosporine, tacrolimus, loop diuretics, NSAIDs and radiographic contrast dye**)
156
Lipoglycopeptides (with the generic name suffix “-vancin”) inhibit bacterial cell wall synthesis by:
Tela**vancin** (Vibativ)
l) binding to the D-alanvl-D:alanine portion of the cell wall, blocking polymerization and cross-linking of peptidoglycan
2) disrupting bacterial membrane potential and changing cell permeability (due to the presence of a lipophilic side chain).
157
Telavancin (Vibativ)
Approved for complicated **skin and soft-tissue infections (SSTI**) and **hospital-acquired** and **ventilator-associated pneumonia**
158
Telavancin (Vibativ)
BBW
* **Fetal risk - obtain pregnancy test prior to starting therapy**
* **Nephrotoxicity; Increased mortality with pre-existing moderate-to-severe renal impairment (CrCI \< 50 mL/min)**
159
Telavancin (Vibativ)
Warnings
Can falsely increse coagulation tests (e.g.. aPTT/PT/INR), but does not increase bleeding risk; red man syndrome with rapid IV administration (give over \> 60 minutes); QT prolongation
160
Oritavancin (Orbactiv)
&
Dalbavancin (Dalvance)
Contraindications
Oritavancin: do not use IV UFH **for 120 hours (5 days)** after oritavancin administration due to interference (false elevations) with aPTT laboratory results
161
Oritavancin (Orbactiv)
&
Dalbavancin (Dalvance)
Can cause falsely increase PT/INR for up to **12 hours and a P IT for up to 120 hours after a dose**
162
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
163
Daptomycin has concentrationdependent activity against most Gram-positive bacteria, including
* Staphylococci (MRSA) and
* Enterococci (both species of VRE, E. faecium and E. faecalis)
## Footnote
**It has no activity against Gram-negative pathogens.**
164
Daptomycin (Cubicin, Cubicin RF)
Warnings
Myopathy and rhabdomyolysis
Can falsely increase PT/INR,
165
Daptomycin (Cubicin, Cubicin RF) Side effects
**Increased CPK**, abdominal pain, pruritus, chest pain, edema, hypertension, acute kidney injury
MONITOR
**CPK level weekly**
166
Cubicin: compatible with NS and LR **(no dextrose)**
Do not use to treat pneumonia; drug is inactivated in the lungs by surfactant
167
**Linezolid and tedizolid** bind to the **50S subunit** of the bacterial ribosome, inhibiting translation and protein synthesis.
They have activity against similar pathogens as vancomycin (e.g., **MRSA**), but also cover **VRE (E. faecium and E. faecalis).**
168
Linezolid (Zyvox)
No renal dose adjustments required **IV:PO ratio is 1:1**
**CONTRAINDICATIONS**
Do not use with or within 2 weeks of MAO inhibitors
WARNINGS
Duration-related myelosuppression (thrombocytopenia
When used \> 14 days, peripheral and optic neuropathy
When used \> 28 days, serotonin syndrome, hypoglycemia
169
Linezolid (Zyvox)
**Do not shake** linezolid suspension
* decrease platelets
* decrease Hgb
* decrease WBC
* HA,
* nausea
* diarrhea
* Increased LFTs
170
Linezolid/Tedizolid Drug Interactions
**Linezolid and tedizolid** are reversible **monoamine oxidase inhibitors**. **Avoid tyramine-containing** foods and serotonergic drugs
171
Tigecycline is a glycylcycline. It binds to the SOS ribosomal subunit inhibiting protein synthesis; structurally, **it is related to the tetracyclines**
Tigecycline has **broad-spectrum**
Among the Gram-negatives, it has no activity against the **“3 P’s": Pseudomonas, Proteus, Providencia species**
172
Tigecycline (Tygacil)
BOXED WARNING
Increased risk of death
NOTES
Do not use for bloodstream infections
Reconstituted solution should be **yellow/orange: discard if not this color**
173
polymyxin class consists of two drugs, colistimethate (sometimes referred to as colistin) and polymyxin B. Colistimethate
Due to the risk of toxicities, they are used primarily for MDR Gram-negative pathogens in combination with other antibiotics.
174
Colistimethate(Coly-Mycin M)
Solutions for **inhalation** must be mixed immediately prior to administration
**Dose-dependent nephrotoxicity** (monitor renal function and electrolytes), neurotoxicity (dizziness, headache, tingling, oral paresthesia, vertigo)
175
Colistimethate is a **prodrug** that is converted to **colistin**
Colistimethate **(Coly-Mycin M)** Injection (can be used for inhalation administration)
176
Polymyxin B
Injection
**BOXED WARNINGS**
Nephrotoxicity (dose-dependent)
Neurotoxicity (dizziness, tingling, numbness, paresthesia, vertigo)
Neurotoxicity can result in **respiratory paralysis** from neuromuscular blockade
177
Chloramphenicol
warnings
**Gray syndrome** with high serum levels - circulatory collapse, cyanosis, acidosis, abdominal distention, myocardial depression, coma and death
178
Clindamycin (Cleocin)
**No renal dose adjustments**
Topical formulations:
**Cleocin-T, Clindasel**
BBW: C-Diff
Notes:
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
179
Metronidazole has activity against **anaerobes and protozoal infection**s
It is effective for **bacterial vaginosis**, **trichomoniasis**, giardiasis, amebiasis, C. difficile (though not preferred) and is used in combination regimens for **intra-abdominal infections**
180
**Metronidazole (Flagyl)**
**Topical**: MetroCream, Metrogel, MetroLotion, Noritate, Rosadan
**Vaginal: Nuvessa, Vandazole**
These antibiotics cause a loss of **helical DNA** structure and strand breakage resulting in **inhibition of protein synthesis**
**lV:PO ratio is _1:1_**
181
Metronidazole (Flagyl) Contraindications
**Pregnancy (1st trimester**)
Use of **alcohol or propylene glycol-containing products** during treatment or **within 3 days** of treatment discontinuation **(disulfiram reaction)**
182
Metronidazole (Flagyl)
Side effect:
Metallic taste,
183
Secnidazole (Solosec)
PO: 2 gram **single dose**
## Footnote
**SOLO = by itself = single dose**
**SE:**
**Vulvovaginal candidiasis, HA, N /D**
184
Metronidazole is a weak inhibitor of CYP2C9 and can cause
an increase INR in patients taking warfarin.
**Metronidazole and tinidazole** should not be used with
alcohol
185
Fidaxomicin **inhibits RNA polymeras**e, resulting in inhibition of protein synthesis and cell death.
It is used for **C. difficile** infections.
WARNINGS
**Not effective for systemic infections** - absorption is minimal
186
**Rifaximin inhibits bacterial RNA** synthesis by binding to bacterial DNA-dependent RNA polymerase. It is structurally related to rifampin.
**Not effective for systemic infections** (\< 1% absorption)
Used ***off-label for C. difficile*** infection
187
Fosfomycin Inhibits **bacterial cell wall synthesi**s by inactivating the enzyme pyruval transferase, which is critical in the synthesis of cell walls.
It has activity against **E. Coli (including ESBLs)** and **E. faecalis (including VRE)**.
A **single-dos**e regimen is used for **uncomplicated UTI (cystitis only)**.
188
Fosfomycin **(Monurol)**
## Footnote
**Packet granules = 3 gram per packet**
Female, **uncomplicated UTI** 3 grams **PO x 1**, mixed in 3 -4 oz of cold water
189
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).
190
Nitrofurantoin
## Footnote
**(Macro**_bid_**, Macrodantin)**
Contraindicated: Renal impairment (CrCI \< 60 ml/min \* )
Warnings: hemolytic anemia (use caution in patients with **G6PD deficiency**)
SIDE EFFECTS:
Gl upset (**take with food**), headache, rash, **brown urine discoloration (harmless)**
191
**KEY FEATURES OF NITROFURANTOIN**
* **Drug of choice for uncomplicated UTI**
* **See the ID II chapter for a discussion on use in pregnancy**
* **Do not use**
* **Contraindicated when CrCI \< 60 mL/min Dosing**
* **Macrobid is BID**
* **Macrodantin is QID**
* **Counseling**
* **Take with food to prevent nausea, cramping**
* **Can discolor the urine (brown)**
192
Mupirocin is a **topical antimicrobial ointmen**t used to **eliminate Staphylococci (MRSA) colonization of the nares**
**Mupirocin _(Bactroban\*)_**
**Mupirocin _(Bactroban\*)_**
**_Decolonization_**
**1/2 tube in each nostril BID X 5 days**
193
Methicillln-**sensitive** Staphylococcus aureus **(MSSA)**
**Dicloxacillin, nafcillin, oxacillin**
**Cefazolin, cephalexin** (and other 1st and 2nd generation cephalosporins)
Amoxiciilin/clavuianate, ampicillin/sulbactam
Doxycycline, minocycline
SMX/TMP
194
Community-associated methicillin resistant Staphylococcus aureus **(CA-MRSA)** Skin & soft tissue infections (**SSTIs)**
**(CA-MRSA** **SSTIs)**
**SMX/TMP (Bactrim)**
**Doxycycline (Vibramycin), minocycline (Minocin)**
**Clindamycin (Cleocin)**
**Linezolid (Zyvox)**
195
**Severe SSTIs** requiring IV treatment or hospitalization (**cover _MRSA_ and **_Streptococc_**i)**
* **Vancomycin** (consider using alternative if MIC \>2)
* **Linezolid**, tedizolid
* **Daptomycin**
* **Ceftaroline**
* Telavancin
* Oritavancin
* Dalbavancln
* Quinupristin/Dalfopristin
* Tigecycline
196
Nosocomial MRSA
**Vancomycin** (consider using alternative if MIC \>2)
**Linezolid**
**Daptomycin** (not in pneumonia)
Telavancin
197
VRE (E.faecalis)
* **Pen G or ampicillin**
* **Linezolid**
* **Daptomycin**
* Tigecycline
* **Cystitis only**: *_nitrofurantoin, fosfomycin, doxycycline_*
198
VRE (E.faecium)
**Daptomycin**
**Linezolid**
Quinupristin/Dalfopristin
Tigecycline
**Cystitis only:** *_nitrofurantoin, fosfomycin, doxycycline_*
199
HNPEK
* **H. influenzae.**
* **Neisseria gonorrhoeae.**
* **Proteus.**
* **E. coli.**
* **Klebsiella**
200
HNPEK
* H. influenzae.
* Neisseria gonorrhoeae.
* Proteus.
* E. coli.
* Klebsiella
* **Beta-lactam/beta-lactamase inhibitor**
* Amoxicillin (if beta-lactamase negative)
* Cephalosporins (except 1st generation)
* Carbapenems
* SMX/TMP
* Aminoglycosides
* Quinolones
201
Atypical Organisms
**Azithromycin**, clarithromycin
**Doxycycline,** minocycline
**Quinolones**
202
Pseudomonas aeruginosa
* **_Piperacillin/tazobactam_**
* **_Cefepime_**
* **_Ceftazidime_**
* **_Ceftazidime/avibactam_**
* **_Ceftolozane/tazobactam_**
* **_Carbapenems (except ertapenem)_**
* **_Ciprofloxacin, levofloxacin_**
* **_Aztreonam_**
* **_Aminoglycosides_**
* **_Colistimethate, polymyxin B_**
203
Acinetobacter baumannii
* **Carbapenems (except ertapenem)**
* Ampiclllln/sulbactam
* Minocycline
* Tigecycline
* Quinolones
* SMX/TMP
* Amikacin
* Colistimethate, polymyxin B
204
Extended-spectrum beta-lactamase producing Gram-negative rods **(ESBL GNR**) - E. coli, K. pneumoniae, P. mirabilis
* **Carbapenems**
* **Ceftazidime/avibactam**
* **Ceftolozane/tazobactam**
* Aminoglycosides
* Cystitis only: fosfomycin
205
Carbapenem-resistant Gram-negative rods (CRE)
* **Ceftazidime/avibactam**
* **Colistimethate, polymyxin B**
* Meropenem/vaborbactam
* Imipenem/cilastatin/relebactam
206
Bacteroides fragilis
* **Metronidazole**
* **Beta-lactam/beta-lactamase inhibitor**
* **Cefotetan, cefoxitin**
* **Carbapenems**
* Tigecycline
* Others (reduced activity): moxifloxacin
207
C. difficile Infection
* **Vancomycin _(oral)_**
* **Fldaxomicin**
* Metronidazole
208
REFRIGERATION REQUIRED AFTER RECONSTITUTION
* **Penicillin VK**
* **Ampicillin**
* **Amoxicillin/Clavulanate (Augmentin)**
* Vancomycin oral (Firvonq)
* Valganciclovir (Valcyte)\*
* Cephalexin (Keflex)
209
REFRIGERATION RECOMMENDED
Amoxicillin - **improves taste**
210
DO NOT REFRIGERATE
* **Cefdinir (formerly Omnicef)**
* Azithromycin
* Clarithromycin - bittertaste, thickens/gels
* Acyclovir (Zovirax)\*
* Fluconazole (Diflucan)'
* Posaconazole (Noxafil)\*
* Voriconazole (Vfend)\*
* Nystatin\*
211
STORAGE REQUIREMENTS: IVANTIBIOTICS
Most IV medications are refrigerated; the list below represents a few that are not.
* **Metronidazole (Flagyl)**
* **Moxifloxacin (Avelox)**
* Sulfamethoxazole/Trimethoprim
* A cyclovir (Zovirax) - refrigeration causes crystallization
212
**Many antibiotics** are cleared through the **_kidneys_** and **_require dose adjustments_** based on renal function. **This includes most _beta-lactams_ and _quinolones_**
What are antibiotics that ***_do not_*** require **_renal adjustment_**
* **Antistaphylococcal penicillins (e.g., dicloxacillin, nafcillin)**
* **Ceftriaxone**
* **Clindamycin**
* **Doxycycline**
* **Macrolides (azithromycin and erythromycin only)**
* **Metronidazole**
* **Moxifloxacin**
* **Linezolid**
213
Most antibiotics can be taken with food to decrease Gl upset
**_Exceptions:_**
**Take on an empty stomach:**
ampiciliin oral capsules and suspension,
ceftibuten suspension,
levofloxacin oral solution,
penicillin VK,
rifampin\*, isoniazid\*, itraconazole solution', voriconazole\*
214
1:1 IV TO ORAL DOSING
For these drugs, the oral and IV doses are the same.
**Levofloxacin,** moxifloxacin
**Doxycycline, minocycline**
**Linezolid**, tedizolid
**Metronidazole**
Sulfamethoxazole/Trimethoprim
Fluconazole\*, isavuconazonium\*, posaconazole\* (oral tablets and IV), voriconazole\*
215
LIGHT PROTECTION DURING ADMINISTRATION
**Doxycycline**
**Micafungin\***
Pentamidine\*
216
DILUENT COMPATIBILITY REQUIREMENTS
Compatible with **_dextrose only_**
**Quinupristin/Dalfopristin**
**Sulfamethoxazole/Trimethoprim**
**Amphotericin B\*** (conventional, Abelcet, Ambisome)
Dalbavancin, oritavancin
Pentamidine\*
217
Compatible with **saline only - 0.9% NS**
**Ampiciliin**
**Ampicillin/Sulbactam**
**Ertapenem**
**Daptomycin** (Cubicin RF - see the daptomycin drug table for reconstitution requirements prior to dilution)
218
Compatible with **NS/LR only**
**Caspofungin\***
**Daptomycin (Cubicin)**
