Nontuberculous Mycobacterial Infections Flashcards
(212 cards)
1
Q
How fast do rapid growers take to grow?
Slow growers?
A
7 days
>14 days
2
Q
What is the v of NTM?
A
In addition to rate of growth, the organism’s ability to produce yellow pigment with or without exposure to light is assessed.
3
Q
What are Photochromogens
A
Slow growing and produce a yellow–orange pigment only in the presence of light exposure.
4
Q
What are Scotochromogens
A
can produce pigment with or without light exposure.
5
Q
What are Nonchromogens
A
Produce no pigment [all rapid growing NTM are this]
6
Q
Name the rapidly growing NTM [6]
A
M. abscessus
7
Q
Name the slow growing Photochromogen NTM [2]
A
M. kansasii
8
Q
Name the slow growing Scotochromogen NTM [2]
A
M. gordonae
M. scrofulaceum
9
Q
Name the slow growing Nonchromogen NTM [9]
A
M. haemophilum M. malmoense M. simiae M. avium M. intracellulare M. chimaera M. ulcerans M. xenopi
10
Q
Which NTM need lower incubation temps [28–30°C] [4]
A
M. conspicuum
M. genavense
M. haemophilum
M. marinum
11
Q
Which NTM needs supplementation with iron [1]
A
M. haemophilum
12
Q
Which NTM needs supplementation with mycobactin [2]
A
M. paratuberculosis
M. genavense
13
Q
Which NTM needs supplementation with egg yolk [1]
A
M. ulcerans
14
Q
Which NTM needs 8-12 week intubation? [2]
A
M. genavense
M. ulcerans
15
Q
Which NTM has in vivo growth only [1]
A
M. leprae
16
Q
Which NTM are recovered almost exclusively from municipal water sources? [3]
A
M. kansasii
M. xenopi
M. simiae
17
Q
Risk factors for NTM disease? [4]
A
bronchiectasis, cystic fibrosis, cigarette smoking, and chronic obstructive pulmonary disease (COPD).
18
Q
Risk factors for disseminated NTM disease? [4]
A
cell-mediated immunodeficiency (e.g., AIDS and steroids use); genetic syndromes with interferon (IFN)-γ or interleukin (IL)-12 pathway defects.
19
Q
Is NTM communicable?
A
No.
No evidence of human-human or animal-human transmission.
20
Q
What are the 5 major clinical syndromes of NTM infection?
A
- Pulmonary disease (75%).
- Lymphadenitis (5%)
- Skin, soft tissue, and bone disease (15%)
- Disseminated disease. (5%)
- Hypersensitivity (0%)
21
Q
Species of NTM most associated with pulmonary infection? [3]
A
MAC
M. kansasii
M. abscessus
22
Q
Species of NTM most associated with lymphadenitis [1]
A
MAC
23
Q
Species of NTM most a/w skin, soft tissue, and bone disease. [6]
A
MAC M. fortuitum group M. chelonae M. abscessus M. marinum M. ulcerans (rare in United States)
24
Q
Species of NTM most a/w disseminated infection in an HIV patient [4]
A
M. avium
M. genavense
M. haemophilum
M. kansasii
25
Species of NTM most a/w disseminated infection in a non HIV patient [2]
M. abscessus
| M. chelonae
26
Species of NTM most a/w hypersensitivity pneumonitis [2]
Metal workers: M. immunogenum
| Hot tub: M. avium
27
How is lung NTM diagnosed?
Combination of BOTH clinical and microbiologic criteria
28
What are the clinical criteria for diagnosis of NTM lung disease? [2]
1. Pulmonary symptoms, nodular or cavitary opacities on chest radiograph, or an HRCT scan that shows multifocal bronchiectasis with multiple small nodules
AND
2. Appropriate exclusion of other diagnoses.
29
What are the microbiologic criteria for diagnosis of NTM lung disease? [3]
1. Positive culture results from at least two separate expectorated sputum samples
OR
2.Positive culture result from at least one bronchial wash or lavage
OR
3. Transbronchial or other lung biopsy with mycobacterial histopathologic features (granulomatous inflammation or AFB) and positive culture for NTM or biopsy showing mycobacterial histopathologic features (granulomatous inflammation or AFB) and one or more sputum or bronchial washings that are culture positive for NTM.
30
What are the 2 major species of MAC?
M. avium
| M. intracellulare.
31
What type of disease does M. intracellulare cause?
NTM lung disease
32
What type of disease does M. avium typically cause
Most common cause of disseminated NTM disease in acquired immunodeficiency syndrome (AIDS) patients.
33
What are the 2 major types of MAC lung disease?
Apical fibrocavitary lung disease
| Nodular bronchiectatic disease
34
Who gets Apical fibrocavitary lung MAC?
males in their 40s–50s with history of cigarette smoking ± excessive alcohol use
35
How does Apical fibrocavitary lung MAC present?
Aggressive, untreated, progresses in 1–2 years to extensive lung cavitation with respiratory failure.
36
How does Nodular bronchiectatic disease lung MAC present?
“Lady Windermere Syndrome”: slowly progressive form. Frequently right middle lobe or lingula affected.
37
Who gets Nodular bronchiectatic disease lung MAC
Postmenopausal, nonsmoking, white females.
| Scoliosis, thin, pectus deformities*, hypomastia
38
Treatment of Apical fibrocavitary lung MAC
rifampin + ethambutol + macrolide (azithromycin or clarithromycin), daily dosing
Amikacin for first 1-2 months if cavitary disease
Treat for 18-24 months or 12 months after achieving culture-negativity.
39
Treatment of Nodular bronchiectatic disease lung MAC?
rifampin + ethambutol + macrolide (azithromycin or clarithromycin), 3x a week
Treat for 12 months after achieving negative cultures
40
Presentation of MAC Disseminated Disease?
Fever in >80% of cases
Night sweats and weight loss less common
May have abdominal tenderness, hepatosplenomegaly, and lymphadenopathy on exam
41
Who gets disseminated MAC?
AIDs with CD4 <50
42
Diagnosis of disseminated MAC?
Culture of MAC from a sterile site
Blood cultures are positive in 90% of cases (increased to 98% by taking a second sample).
Other possible culture sites: bone marrow, lymph node, or liver
43
Treatment of disseminated MAC?
Macrolide (clarithromycin or azithromycin) + ethambutol ± Rifabutin
ART therapy
44
Difference between clarithromycin and azithromycin in treated MAC?
Clarithromycin has more rapid clearance of MAC.
| Azithromycin is better tolerated and has fewer drug interactions.
45
How long should disseminated MAC treatment continue? [3]
1. Clinical response for at least 3 months.
2. Good viral load response to ART (<50 copies/mL on two consecutive occasions).
3. Good CD4 count response to ART (>100 cells/μL on two occasions at least 3 months apart).
46
What is hot tub lung
Hypersensitivity lung disease associated with MAC exposure caused by exposure related to undrained pool or spa with overgrowth of MAC (resistant to disinfectants).
47
Treatment of MAC Hypersensitivity Pneumonitis
Controversial..
1. removal of the source (e.g., hot tub)
2. ± steroids,
3. Short course antimicrobial therapy (3–-6 months) depending on clinical response and disease severity.
48
Diagnosis of MAC hypersensitivity pneumonitis?
Clinical, radiologic, and microbiologic criteria
49
What is the clinical criteria for MAC hypersensitivity pneumonitis
1. Subacute respiratory symptoms (dyspnea, cough, and fever)
AND
2. Hot tub exposure
50
What is the radiologic criteria for MAC hypersensitivity pneumonitis
1.Diffuse infiltrate with nodularity
±
2.Ground glass opacity and mosaic pattern
51
What is the microbiologic criteria for MAC hypersensitivity pneumonitis
MAC isolate in sputum, bronchoalveolar lavage, tissue, and hot-tub water
52
Procedures a/w M. chimaera infection? [6]
1. Heart valve surgery (replacement or repair)
2. CABG
3. Heart transplant
4. heart–lung transplant
5. left ventricular assist device (LVAD) implantation
6. vascular grafts.
53
Presentation of M. chimaera infection?
fever, malaise, weight loss,
Endocarditis, chronic sternal wound infection.
May disseminate to liver, bone marrow, lung, skin, brain, lymph nodes, and bone (spine).
Incubation period median of 19 months (range: 3 months to 5 years).
54
Lab abnormalities a/w M. chimaera infection
Lymphopenia
elevated alkaline phosphatase
severe disseminated infection
55
Risk factors for M. kansasii infection? [6]
```
Pneumoconiosis
Chronic obstructive pulmonary disease
Previous mycobacterial disease
Malignancy
Alcoholism
HIV
```
--> Mostly effects middle aged white men
56
Reservoir M. kansasii
Tap water
57
Where is M. kansasii most prevalent
SE. England, Wales, Central and Southern US
58
How does M. kansasii present?
Pulmonary or disseminated disease.
59
Describe M. kansasii pulmonary disease
Similar to pulmonary TB
Upper lobe predilection and cavitary disease are common
Nodular bronchiectatic lung disease similar to MAC reported
60
How does disseminated M. kansasii present?
Common in those with AIDs
| Unlike MAC disseminated disease, 50% of cases also have pulmonary disease.
61
Treatment of M. kansasii
Rifampin, isoniazid, and ethambutol.
| 12 months from culture negativity.
62
What drug should be tested to ensure it is sensitive in the treatment of M. kansasii?
Rifampin
63
What are the 3 M. abscessus subsp?
abscessus
massiliense
bolletii
64
Where is M. abscessus prevalent?
southeastern US states (Florida to Texas).
65
How does M. abscessus present?
Effects skin, soft tissues, bones.
ulcerations, abscesses, draining sinuses, or nodules
Usually resulting from trauma or surgery (e.g., cosmetic surgeries).
66
Describe how M. abscessus lung disease prevalence?
Third most common cause of NTM lung disease.
| Responsible for about 80% of pulmonary disease caused by RGM
67
Who gets M. abscessus lung disease [risk factors]? [7]
white female nonsmokers in their 60s
Bronchiectasis
Prior mycobacterial disease
68
Presentation of M. abscessus lung disease?
Similar to that of MAC lung disease, though only 15% develop cavitary lesions.
69
What is erythromycin resistance methylase (erm) gene?
Gene that causes inducible resistance to macrolides.
| M. abscessus subsp. massiliense lacks this gene. Bolletti and abscessus subspecies almost always have this gene.
70
Treatment principles of M. abscessus
Usually 2 out of 3 of the following medications are used..
1. Tigecycline
2. Imipenem
3. Amikacin [TIW to reduce SE]
Generally resistant to..
1. Linezolid
2. Moxifloxacin
3. Cefoxitin
--> Due to resistance usually requires IV therapy.
71
Management of M. abscessus?
1. drainage of all abscesses and removal of any infected foreign bodies.
Severe skin, soft tissue 4 months.
Bone disease treat 6 months.
Pulmonary disease 12 months from negative culture.
72
Range of M. chelonae presentation?
Skin, soft tissue, and bone disease are the most important clinical manifestations.
Status post plastic surgery with implant placement is classic.
Disseminated skin infection is seen in immunocompromised.
Keratitis have been associated with contact lenses and ocular surgeries (e.g., Lasik).
NTM in the eye is almost EXCLUSIVELY M. chelonae
--> Pulm disease uncommon
73
Treatment of M. chelonae [4]
Macrolide and a companion drug, based on susceptibility testing.
Companion drug options..
tobramycin
74
How long do you treat M. chelonae infection? [3]
Skin and soft tissue infection 4 months.
Bone infection 6 months.
Pulmonary infection 12 months from negative culture.
75
Risk factors for M. fortuitum infection?
Whirlpool footbaths during pedicure procedures in nail salons.
76
Presentation of M. fortuitum infection?
Skin, bone, and soft tissue infections
Responsible for 60% of localized cutaneous NTM infections in previously healthy individuals.
--> NO PREDILECTION FOR IMMUNOCOMPROMISED
77
Treatment of M. fortuitum? [6]
First Line
Quinolones and/or Doxycycline for 4 months
```
Alt
Minocycline
Aminoglycosides
Sulfamethoxazole–trimethoprim
Macrolides
```
78
Why must macrolides in M. fortuitum infection be used with caution?
Carries the erm gene
79
How is M. leprae cultured?
In the footpad of immunodeficient mice.
80
How is M. leprae transmitted? [5]
```
nasal secretions and respiratory droplets
transplacental
breast-feeding
skin contact
Armadillos.
```
81
How does leprosy present?
Hypopigmented skin lesions with hypoesthesia
Lesions can also be erythematous and infiltrative
weakness, autonomic dysfunction, and peripheral nerve thickening.
82
What are the two subtypes of leprosy
tuberculoid (paucibacillary)
| lepromatous (multibacillary)
83
Describe findings of tuberculoid leprosy
<5 lesions
Macules or plaques that are hypoesthetic
Limited to skin and nerves
84
Describe findings of lepromatous leprosy
Innumerable lesions which are nodules, papules, macules, or infiltrative dermopathy.
Skin sensation is intact but it may effect multiple systems including eye, nasal mucosa, nerves, kidney, and bone
85
Describe the pathophysiologic findings of tuberculoid leprosy
Well formed granulomas with Absent to rare acid fast bacilli and abundant lymphocytes.
86
Describe the pathophysiologic findings of lepromatous leprosy
Abundant acid fast bacilli but NO granulomas and few lymphocytes
87
What is the reversal reaction?
Results from the development of exuberant local T-cell-mediated immune response directed at living or dead bacilli. Manifests as increased warmth, erythema, and edema of preexisting lesions and if left untreated can lead to permanent nerve damage.
88
What is Erythema nodosum leprosum
Acute development of new subcutaneous nodules that are red, painful, and tender due to complement activation following immune complex deposition.
89
Diagnosis of leprosy?
Clinical exam and slit-skin testing is used to make the diagnosis in endemic countries
Histopathological examination of skin biopsy is the gold standard.
--> Serologic tests and PCR if limited use and availability.
90
Treatment of PB leprosy?
| Treatment of MB leprosy?
Dapsone + Rifampin [monthly] for 6 months
Dapsone + Rifampin [monthly] + Clofazamine [daily and monthly] for 12 months
91
Treatment of reversal reaction?
Clofazimine
| Steroids
92
Treatment of erythema nodosum leprosum
Steroids
| Thalidomide
93
What type of disease does M. genavense cause? [1]
Disseminated disease in AIDs patient
--> If cultures are negative and disease is suspected this is the likely pathogen as it needs multiple special conditions to grow.
94
If you see M. gordonae what should you think.
CONTAMINANT
| --> Patient drinking or rinsing with tap water prior to respiratory specimen collection
95
What type of disease does M. immunogenum cause? [3]
Central venous catheter-related bacteremia
Hypersensitivity pneumonitis due to metalworking fluid contamination
Skin infection
96
What type of disease does M. mucogenicum cause? [2]
Central venous catheter-related bacteremia
Peritoneal catheter-related peritonitis
--> Contaminant if found in lungs
97
What type of disease does M. smegmatis cause? [2]
Pulmonary disease in patients with lipoid pneumonia
| Rare cause of skin, soft tissue, and bone disease
98
What drug is M. smegmatis resistant to?
Macrolides
99
What should you think if M. szulgai is found in culture?
IT IS SIGNIFICANT
| --> No usually found in environment
100
Type of disease M. terrae complex causes?
hand tenosynovitis
101
What type of disease does M. ulcerans cause?
Chronic necrotic progressive ulcer of skin and soft tissues (Buruli ulcer).
Think of this in a tropical setting
- -> Rare in US
- -> 3rd most common mycobacterial disease world wide [after TB and leprosy]
102
What type of disease does M. xenopi cause?
Pulmonary disease with apical cavitation, more commonly in COPD
103
Reservoir for M. xenopi?
Hot water systems.
| Found in Northern US, Canada, Europe
104
What are the WHO Group A anti-tuberculosis drugs? [2]
Moxifloxacin
| Levofloxacin
105
What are the WHO Group B anti-tuberculosis drugs? [4]
Streptomycin (SM)
Amikacin
Kanamycin
Capreomycin
106
What are the WHO Group C anti-tuberculosis drugs? [4]
Ethionamide
Prothionamide
Cycloserine
Linezolid
107
What are the WHO Group D anti-tuberculosis drugs? [4]
Para-aminosalicylic acid
Bedaquiline
Carbapenems
Delamanid
108
MOA of aminoglycosides?
irreversibly binding to the bacterial 30S ribosome subunit; bactericidal.
109
Role of aminoglycosides in the treatment of MAC? [3]
Consider in extensive fibrocavitary pulmonary MAC disease.
Patients who have failed prior drug therapy.
Macrolide-resistant MAC infection.
110
Other possible uses for aminoglycosides in treatment of NTM?
- -> Rifampin resistant M. kansasii
| - -> M. chimera infection
111
Aminoglycosides SE [3]
Nephrotoxic
Ototoxic
Neuromuscular blockade [myasthenia gravis], esp with kanamycin
112
Monitoring for patients on aminoglycosides? [3]
Renal function: weekly or biweekly
Audiology exams: monthly and if eighth nerve toxicity symptoms occur.
Drug levels: weekly
113
Dosing considerations for aminoglycosides?
- -> Renal adjustment
| - -> Weight adjustment
114
MOA of Bedaquiline
Inhibits the activity of mycobacterial ATP synthase by binding to its c subunit, which prevents the bacterium from generating ATP, ultimately leading to cell death; bactericidal.
115
Clinical use of bedaquiline?
Treatment for M. tuberculosis that is extensively drug-resistant
116
Bedaquiline side effects?
Nausea, arthralgia, headache, QTc prolongation, hepatotoxicity, increased risk of death.
117
Bedaquiline drug interactions
Substrate of CYP3A, and thus drugs that induce or inhibit CYP3A can affect exposure of bedaquiline.
118
Bedaquiline monitoring while on therapy? [3]
CMP [LFTs, alk phos, bili]
EKG at baseline than at 2, 12, 24 weeks; DC medications of QTc >500ms
Symptoms of liver issues [fatigue, nausea, anorexia, jaundice, dark urine, liver tenderness]
119
Bedaquiline dosing considerations?
TAKE WITH FOOD
| --> Enhances absorption 95%
120
MOA of Capreomycin
Inhibits bacterial protein synthesis by interacting with the bacterial ribosome.
--> Not well understood
121
Side effects of capreomycin [2]
Nephrotoxicity
| Ototoxicity
122
Monitoring for Capreomycin [3]
audiometric measurements and vestibular function at baseline and during therapy
CMP at baseline and weekly
Magnesium baseline and weekly
123
Describe NTM susceptibility to imipenem
>90% of M. fortuitum group are susceptible
40–60% of M. chelonae
40–60% M. abscessus are susceptible.
124
Side effects of imipenem? [8]
seizures, nausea, vomiting, diarrhea, abnormalities in LFTs, neutropenia, eosinophilia, rash.
125
Important drug drug interactions with imiepnem?
valproic acid: decreases concentration
| Ganciclovir: increases risk of fever
126
Clinical use of cefoxitin in the treatment of NTM?
Empiric or definitive treatment of M. abscessus, M. chelonae, and M. fortuitum [RGM]
While awaiting further identification and susceptibility results, cefoxitin may be initiated for empiric treatment of rapidly growing mycobacterial infection; typically used in combination with amikacin and macrolides.
127
Cefoxitin side effects? [5]
diarrhea, eosinophilia, rash, hemolytic anemia (rare), pancytopenia (rare)
128
NOTE:
No one knows how Clofazimine works
129
Clinical use for Clofazimine
Combination therapy for lepromatous (multibacillary) leprosy.
--> Counts as half a drug in a treatment regimen of TB
130
Side effects of clofazimine? [6]
1. abdominal pain, nausea, vomiting, diarrhea
2. reddish-black or orange skin discoloration within a few weeks of starting clofazimine
3. Discoloration in hair, urine, sweat, feces, sputum, and other bodily fluids,
4. reddish-brown corneal and conjunctival discoloration, 5. lymphedema (rare)
6. exfoliative dermatitis (rare.)
--> Adverse effects related to clofazimine are dose-related and result from its long half-life and tendency to crystallize in fatty tissue. Thus side effects are usually slowly reversible upon discontinuation.
131
Clofazimine drug interactions?
co-administration with aluminum-magnesium antacid reduces bioavailability
132
Clofazimine dosing considerations?
Administer with food
133
Mechanism of action of Cycloserine
Competitively inhibiting at least two bacterial enzymes that either supply D-alanine for or incorporate D-alanine into peptide bridges which assist in maintaining the integrity of the bacterial cell wall.
134
Clinical use of Cycloserine
Second line for TB
135
Cycloserine SE? [3]
neurotoxicity (convulsion, somnolence, confusion, tremor, vertigo, drowsiness), elevated LFTs, rash.
136
Contraindications to cycloserine use? [5]
epilepsy; depression/anxiety, or psychosis; severe renal insufficiency; excessive concurrent use of alcohol.
137
Significant drug interactions to note with cycloserine use? [2]
1. Use with EtOH increases risk of seizures
| 2. CNS toxicity enhanced with isoniazid
138
Routine monitoring with cycloserine? [2]
1. neuropsychiatric status at monthly intervals
| 2. Plasma concentration levels
139
How might the neurotoxic effects of cycloserine be mitigated?
pyridoxine
140
MOA of dapsone?
Acts on folic acid synthesis pathway by inhibiting the enzyme dihydropteroate synthase (DHPS).
141
Clinical use of dapsone in treatment of TB/NTM?
Leprosy treatment
142
Dapsone SE? [6]
```
rash
methemoglobinemia
hemolysis
agranulocytosis
aplastic anemia
hepatotoxicity.
```
143
Dapsone drug interactions? [2]
rifampin increases metabolism.
| Probenecid blocks renal excretion
144
Required monitoring for dapsone? [4]
1. CBC with differential (weekly for the first month, monthly for 6 months, then semiannually)
2. reticulocyte count
3. liver function tests
4. monitor for signs of jaundice, hemolysis, or methemoglobinemia.
145
Delamanid MOA?
Nitro-dihydro-imidazooxazole drug that inhibits mycolic acid synthesis
146
Clinical use of Delamanid?
Third-line agent for MDR-TB
XDR-TB agent
NOT FDA APPROVED
147
Delamanid side effects? [3]
rash, nausea, vomiting; QTc prolongation
148
Delamanid contraindications
1. Pregnancy
| 2. Hypoalbuminemia
149
Delamanid monitoring considerations
1. Baseline and monthly ECGs
| 2. Serum albumin baseline and monthly
150
Ethambutol MOA
Inhibits arabinofuranosyltransferase enzymes that are involved in polymerizing arabinofuranosyl (Araf) residues from DPA into the arabinan components of mycobacterial cell wall arabinogalactan and lipoarabinomannan; bacteriostatic.
151
Clinical use of ethambutol in the treatment of NTM [3]
May be included in regimen against..
| M. avium complex, M. kansasii, and M. marinum.
152
Ethambutol SE [6]
optic neuritis, peripheral neuritis, nephrotoxicity, rash, liver dysfunction, thrombocytopenia (rare).
153
Drug interactions with ethambutol?
aluminum hydroxide may decrease the serum concentration
154
Monitoring with ethambutol? [1]
visual acuity and color discrimination testing: baseline and monthly
155
What organ metabolized ethemabutol?
Kidney
| --> DOSE ADJUST
156
MOA of Ethionamide?
Interfere with the production of mycolic acids thus disrupting the lipid membrane of mycobacteria.
157
Clinical use of ethionamide?
Core second-line agent for treatment of MDR-TB infection.
158
Ethionamide SE? [4]
1. gastrointestinal (i.e., nausea, vomiting, abdominal cramps, diarrhea, metallic taste, anorexia), hepatotoxicity 2. neurologic toxicity (e.g., depression, drowsiness, headache, peripheral neuritis, blurred vision, diplopia)
3. drug rash with eosinophilia and systemic symptoms (DRESS)
4. Stevens–Johnson syndrome (SJS), toxic epidermal necrolysis (TEN).
159
What reduces neuro SE of ethionamide?
pyridoxine
160
Ethionamide monitoring?
1. Baseline and monthly LFTs
2. Baseline and periodic ophthalmic exams
3. Blood glucose and TSH
161
MOA of fluoroquinolones?
Inhibits DNA gyrase and DNA topoisomerase IV. These two enzymes work together in replication, transcription, recombination, and repair of DNA; bactericidal
162
Role of fluoroquinolones in treatment of TB?
Used against drug-resistant tuberculosis or when first-line agents cannot be used because of intolerance.
163
Role of fluoroquinolones in treatment of NTM?
Treatment of...
Rifampin-resistant M. kansasii.
M. fortuitum infections
164
NTM generally resistant to cipro? [3]
M. chelonae, M. abscessus, and M. immunogenum
165
CNS side effects of fluroquinolones?
Dizziness, confusion, hallucinations, seizures, toxic psychosis, insomnia.
Peripheral neuropathy: may be irreversible – discontinue at first signs of sensory or sensorimotor neuropathy.
166
Fluroquinolone dosing consideration
Calcium, iron, multivitamins with minerals, antacids, dairy: fluoroquinolones chelate with divalent cations, significantly decreasing bioavailability
--> Administer quinolones 2 hours before OR 6 hours after eating any of the above.
167
Which fluroquinolone does NOT need renal adjustment?
Moxifloxacin
168
Role of bactrim in treating NTM? [2]
Cutaneous disease caused by M. marinum
--> MAY BE SINGLE AGENT IN MILD DISEASE
Used in combination treatment of M. fortuitum.
169
Important bactrim drug interactions? [2]
Warfarin: (attributed to the sulfonamide component of the combination) increases INR.
Rifampin: reduces plasma concentration trimethoprim–sulfamethoxazole
170
NOTE:
Cross reactivity with anaphylaxis between antibiotic sulfonamides and nonantibiotic sulfonamides MAY NOT OCCUR [if allergic to lasix, may be okay to use bactrim].
171
MOA of isoniazid?
Inhibits synthesis of mycolic acids, a critical component of the lipid-rich mycobacterial cell wall.
Bactericidal
172
How is isoniazide metabolized and what is the significance
Liver via hepatic acetylation.
Fast acetylators: may require higher dose for same effect.
Slow acetylators: higher risk of toxicity (neuro and hepatic).
173
Isoniazide SE [4]
hepatotoxicity (1%–2.7%), neurotoxicity (<0.2%), nausea, vomiting, diarrhea, rash (2%), acute pancreatitis, drug induced lupus
174
Contraindications to isoniazide use? [3]
Acute liver disease
History of liver issues on isoniazide therapy
previous severe adverse reaction (drug fever, chills, arthritis) to isoniazid.
175
Clinical use of linezolid for TB infections
Second-line therapy for treatment of M. tuberculosis infection.
176
Clinical use of linezolid for NTM infections
Severe pulmonary infections with M. abscessus (both initial and maintenance therapy).
177
Linezolid SE [4]
nausea, vomiting, diarrhea.
myelosuppression
peripheral and optic neuropathy
lactic acidosis.
178
Monitoring for patients on linezolid? [2]
1. CBC (weekly)
| 2. visual function in patients requiring ≥3 months of therapy or in patients reporting new visual symptoms.
179
What is the bioavilability of PO linezolid?
100% [IV = PO]
180
MOA of macrolides?
Inhibit bacterial protein synthesis by binding to 50S ribosome subunit; bacteriostatic.
181
Clinical use of macrolides in tx of NTM/TB [3]
1. Cornerstone of MAC treatment
2. rifampin-resistant (RR) M. kansasii.
3. M. abscessus and other RGM
182
Treatment for secondary MAC prophylaxsis
Azithro + ethambutol or rifampin
183
How are macrolides metabolized? [3]
Kidneys [Renal dose adjustment]
ALSO induce CYP
Clarithromycin is a potent CYP3A4 inhibitor
184
Macorlide SE [4]
GI
Hepatic necrosis and failure [caution with pre-exisitng liver disease]
eosinophilia, fever, skin eruptions
Leukopenia, thrombocytopenia
185
Medications in which use of azithromycin is contraindicated? [4]
cisapride, pimozide, ergot alkaloids (e.g., ergotamine, dihydroergotamine), or HMG-CoA reductase inhibitors extensively metabolized by CYP3A4 (e.g., lovastatin, simvastatin)
186
MOA of Para-aminosalicylic Acid (PAS)
Structurally related to para-aminobenzoic acid (PABA); its mechanism of action is thought to be similar to the sulfonamides, a competitive antagonism with PABA; bacteriostatic.
187
Clinical use of Para-aminosalicylic Acid (PAS)?
Treatment of resistant M. tuberculosis infection in combination with other antituberculous medications.
188
PAS SE? [6]
GI
Hypothyroidism
hepatitis, neutropenia, agranulocytosis, renal impairment
189
MOA of pyrazinamide
is converted to pyrazinoic acid in susceptible strains of mycobacteria, exact MOA is unknown
More active in acidic environment (e.g., inside macrophages) and against dormant/semi-dormant bacilli.
190
Pyrazinamide SE
hepatotoxicity
hyperuricemia
polyathralgia
thrombocytopenia [rare]
191
Contraindications to Pyrazinamide [2]
Acute gout
| Severe hepatic damage
192
Drug interactions to consider with Pyrazinamide?
Increase concentration of cyclosporin
| enhance the hepatotoxic effect of rifampin
193
MOA of Rifamycins
Inhibit the beta-subunit of DNA-dependent RNA polymerase, blocking elongating RNA transcript. Bactericidal
194
Role of Rifabutin in TB treatment?
Used as a substitute for rifampin; reserved for patients who are receiving any medication having unacceptable interactions with rifampin
195
Role of Rifapentine in TB treatment?
Used once weekly with isoniazid in special patient populations.
196
Side effects of rifamycins? [6]
rash (up to 6% with RIF), hepatotoxicity (1%–2.7%), hemolytic anemia, leukopenia, thrombocytopenia (especially with high-dose therapy), acute renal failure.
197
Rifamycin drug interactions? [9]
```
macrolides
azoles
caspofungin
oral contraceptives
methadone
protease inhibitors
corticosteroids
benzodiazepine
Increases INR in warfarin patients
```
198
MOA of tetracyclines?
Inhibit protein synthesis by binding to bacterial 30S ribosome subunits; bacteriostatic.
199
Clinical use of tetracyclines in mgmt of NTM?
Treatment of M. leprae infection.
| Combination therapy of NTM infections especially RGMs and M. marinum.
200
SE of tetracyclines? [4]
```
tissue hyperpigmentation
vestibular toxicity (minocycline)
pill-associated esophagitis (doxycycline)
intracranial hypertension (doxycycline).
```
201
SE of Tigecycline [2]
Hepatotoxicity
| Pancreatitis
202
Tetracycline drug interactions?
Atazanavir + minocycline may lead to decrease in atazanavir plasma concentrations.
tetracyclines chelate with divalent cations, significantly decreasing bioavailability. Separate by at least 2 hours.
203
Of RIPE therapy what is the likelihood of liver toxicity?
INH >> PZA >> Rifampin
204
Risk factor for M. fortuitum lung disease?
aspiration
- -> GERD
- -> Vomiting.
205
NOTE:
Not all with NTM pulmonary disease need treatment.
Some spontaneously regress
If patient's symptoms [or radiograph] advance or are bothersome - treat
206
Oral medications that generally work against M. abscessus
1. Clofazimine
| 2. Clarithromycin [only M. massiliense]
207
RGM incubation period for SSTI?
2-3 months
208
Treatment of M. marinum?
Macrolide + Bactrim
Macrolide + rifampin [alt],
Other agents that work
doxycycline
ethambutol
--> Use 2 drugs in combination for 3-4 months
Often need hand surgery.
209
What exposure is a/w M. chelonae SSTI?
Tattoo ink contaminated with tap water
210
If a patient is diagnosed with disseminated MAC with HIV when should you start MAC therapy and HIV therapy?
Start MAC therapy first
Wait 2 weeks
Start HAART
--> Reduces risk of IRIS
211
Which medication increases risk of death in NTM in HIV and should be avoided?
Clofazimine
212
Most common disseminated NTM in a cancer patient?
M. chelonae
