Table 1: Suggested Drugs for Scotochromogenic Mycobacterial Diseases
|
Primary Agents |
Alternatives |
|
Macrolides: clarithromycin*; azithromycin |
Aminoglycosides: amikacin; streptomycin |
|
Rifamycins*: rifampin; rifabutin |
Fluoroquinolones: ciprofloxacin, levofloxacin, moxifloxacin |
|
Ethambutol |
Riminophenazine: clofazimine |
|
|
Oxazolidinone: linezolid |
|
|
Isoniazid |
*Note predictable drug interaction between clarithromycin and the rifamycins; rifampin > rifabutin induces the catabolism
of clarithromycin resulting in substantially reduced bioavailability (97). The clinical significance of this has not been established,
but given the preeminent activity of clarithromycin against many NTMs, I would recommend checking drug levels and/or
dosing clarithromycin in the high range. Conversely, clarithromycin inhibits the catabolism of the rifamycins resulting in a
variety of clinical complications including uveitis, pseudo jaundice, arthralgias/myalgias, and a drug-induced lupus syndrome (6).
Table 2: Recommended Antimycobacterial Dosages
|
Drug |
Age |
Daily Regimen |
|
Three Times Weekly |
|
|
|
|
Target Dose (Range) by Weight |
Maximum Dose |
Target Dose (& Range) by Weight |
Maximum Dose |
|
Clarithromycin (PO) |
Pediatric§ |
15 mg/kg/day div QD |
1000 mg |
15 mg/kg/day div QD |
1000 mg |
|
|
Adult |
15 mg/kg/day div QD |
1000 mg |
15 mg/kg/day div QD |
1000 mg |
|
|
Geriatric |
15 mg/kg/day div QD |
1000 mg |
15 mg/kg/day div QD |
1000 mg |
|
Azithromycin (PO) |
Pediatric§ |
5 (5-10) mg/kg/day div QD |
500 mg |
10 (5-10) mg/kg/day div QD |
600 mg |
|
|
Adult |
5 (5-10) mg/kg/day div QD |
500 mg |
10 (5-10) mg/kg/day div QD |
600 mg |
|
|
Geriatric |
5 (5-10) mg/kg/day div QD |
500 mg |
10 (5-10) mg/kg/day div QD |
600 mg |
|
Ethambutol† (PO) |
Pediatric |
15 (15-20) mg/kg/day div QD |
1000 mg |
25 (25-30) mg/kg/day div QD |
2400 mg |
|
|
Adult |
18 (15-20) mg/kg/day div QD |
1600 mg |
25 (25-30) mg/kg/day div QD |
2400 mg |
|
|
Geriatric |
18 (15-20) mg/kg/day div QD |
1600 mg |
25 (25-30) mg/kg/day div QD |
2400 mg |
|
Rifampin (PO) |
Pediatric§ |
10 (8-12) mg/kg/day div QD |
600 mg |
10 (8-12) mg/kg/day div QD |
600 mg |
|
|
Adult |
10 (8-12) mg/kg/day div QD |
600 mg |
10 (8-12) mg/kg/day div QD |
600 mg |
|
|
Geriatric |
10 (8-12) mg/kg/day div QD |
600 mg |
10 (8-12) mg/kg/day div QD |
600 mg |
|
Rifabutin (PO) |
Pediatric |
5 (5-10) mg/kg/day div QD |
300 mg |
5 (5-10) mg/kg/day div QD |
600 mg |
|
|
Adult |
5 mg/kg/day div QD |
300 mg |
5 (5-10) mg/kg/day div QD |
600 mg |
|
|
Geriatric |
5 mg/kg/day div QD |
300 mg |
5 (5-10) mg/kg/day div QD |
600 mg |
|
Amikacin† (IV) |
Pediatric |
15(15-22.5) mg/kg†/day div QD |
1000 mg |
15 (15-22.5) mg/kg/day div QD |
1000 mg |
|
|
Adult |
15(15-22.5) mg/kg†/day div QD |
1000 mg |
15 (15-22.5) mg/kg†/day div QD |
1000 mg |
|
|
Geriatric |
15(15-22.5) mg/kg†/day div QD |
1000 mg |
15 (15-22.5) mg/kg†/day div QD |
1000 mg |
|
Streptomycin‡ (IV) |
Pediatric |
20 (20-30) mg/kg/day div QD |
1000 mg |
20 (20-30) mg/kg/day div QD |
1000 mg |
|
|
Adult |
15 mg/kg/day div QD |
1000 mg |
15 mg/kg/day div QD |
1000 mg |
|
|
Geriatric |
10 mg/kg/day div QD |
750 mg |
10 mg/kg/day div QD |
750 mg |
|
Ciprofloxacin (PO)* |
Pediatric§ |
20 (20-30) mg/kg/day |
1500 mg |
20 (20-30) mg/kg/day div BID |
1500 mg |
|
|
Adult |
30 (20-30) mg/kg/day |
1500 mg |
30 (20-30) mg/kg/day div BID |
1500 mg |
|
|
Geriatric |
20 (20-30) mg/kg/day |
1500 mg |
20 (20-30) mg/kg/day div BID |
1500 mg |
|
Clofazimine (PO) ¥ |
Pediatric |
1-2 mg/kg/day div QD |
100 mg |
No recommendation |
|
|
|
Adult |
1-2 mg/kg/day div QD |
100 mg |
No recommendation |
|
|
|
Geriatric |
1-2 mg/kg/day div QD |
100 mg |
No recommendation |
|
|
Isoniazid (PO) |
Pediatric |
10 (10-15) mg/kg/day div QD |
300 mg |
No recommendation |
|
|
|
Adult |
5 (5-10) mg/kg/day div QD |
300 mg |
No recommendation |
|
|
|
Geriatric |
5 (5-10) mg/kg/day div QD |
300 mg |
No recommendation |
|
|
Linezolid (PO) |
Pediatric |
No recommendation |
300 mg |
No recommendation |
|
|
|
Adult |
600 mg QD¶ |
1200 mg |
No recommendation |
|
|
|
Geriatric |
No recommendation |
1200 mg |
No recommendation |
|
§ Available in a pediatric suspension formulation.
† Dosage based on ideal body weight:
Men: 50 kg plus 2.3 kg/in over 5 feet of height.
Women: 45 kg plus 2.3 kg/in over 5 feet of height.
‡ Dosage based on ideal body weight plus 40% of the excess weight.
* Ciprofloxacin is not a drug of first choice in the pediatric population due to reported adverse events related to joints and/or surrounding tissues.
However, the American Academy of Pediatrics has stated that once risks and benefits have been assessed, it may be justified to use a fluoroquinolone
in mycobacterial infections caused by isolates susceptible to one.
¥ Start clofazimine with dose of 1-2 mg/kg/day up to a maximum of 100 mg once daily, until skin pigmentation appears; then 50 mg once daily;
may reduce to 50 mg thrice weekly after skin bronzing is present.
¶ The recommended frequency of administration of linezolid for acute bacterial infections is 10 mg/kg. However, for chronic mycobacterial pulmonary
disease such as tuberculosis (and by extrapolation presumably for chronic NTM disease as well), some experts are prescribing it once-daily, as this
frequency appears to also be effective, with the possible advantage of being less likely to cause the long-term use-related adverse effects of neuropathy
(peripheral and optic) and anemia. However, in one small prospective study of eight patients, the risk of neurotoxicity was not reduced, although it did
reduce hematological adverse effects (105).