Improved Outcomes With High-dose Isoniazid in Multidrug-resistant Tuberculosis Treatment in Haiti

Walsh, Kathleen F.; Vilbrun, Stalz Charles; Souroutzidis, Ariadne; Delva, Sobieskye; Joissaint, Guy; Mathurin, L; Ocheretina, Oksana; Crémieux, Pierre‐Yves; Pape, Jean William; Koenig, Serena P.

doi:10.1093/cid/ciz039

Cited by 28 publications

(24 citation statements)

References 6 publications

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“…Isoniazid, ethambutol, and prothionamide are included mainly for additional protection of the core drug. High-dose instead of normal-dose isoniazid is preferred because a higher concentration has been shown to overcome low-level resistance and may be particularly useful for patients with thioamide cross-resistance [19,20]. Prothionamide is given only during the intensive phase to limit frequent gastrointestinal adverse events, often responsible for loss to follow-up.…”

Section: Composition Of the Initial Regimenmentioning

confidence: 99%

Short-Course Regimen for Multidrug-Resistant Tuberculosis: A Decade of Evidence

Trébucq

Decroo

Deun

et al. 2019

JCM

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About ten years ago, the first results of the so-called “Bangladesh regimen”, a short regimen lasting nine months instead of 20 months, revolutionized multidrug-resistant tuberculosis (MDR-TB) treatment. Similar short regimens were studied in different settings, relying for their efficacy on a later generation fluoroquinolone, either gatifloxacin, moxifloxacin, or levofloxacin. We review the published material on short MDR-TB regimens, describe their different compositions, their results in national tuberculosis programs in middle- and low-income countries, the risk of acquiring resistance to fluoroquinolone, and the occurrence of adverse events. With over 80% success, the regimen performs much better than longer regimens (usually around 50%). Monitoring of adverse events allows adapting its composition to prevent severe adverse events such as deafness. We discuss the current applicability and usefulness of the short injectable-containing regimen given the 2019 recommendation of the World Health Organization (WHO) for a new long all-oral regimen. We conclude that the most effective fluoroquinolone is gatifloxacin, currently not listed as an essential medicine by WHO. It is a priority to restore its status as an essential medicine.

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Section: Composition Of the Initial Regimenmentioning

confidence: 99%

Short-Course Regimen for Multidrug-Resistant Tuberculosis: A Decade of Evidence

Trébucq

Decroo

Deun

et al. 2019

JCM

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“…Published data on the influence of genotype on treatment outcomes of RsHr-TB are conflicting, study from Vietnam, suggest that katG mutations and not inhA are associated with unfavorable treatment outcomes [33]. Whereas in a study from South Africa, no evidence was found suggesting that specific isoniazid resistance conferring mutations are associated with poor treatment outcomes, and results showed that patients with katG mutations had greater odds of successful outcome when treated with high-dose isoniazid compared to those who received standard dose [34].Few studies have also evaluated the effectiveness of high-dose isoniazid in patients with DRTB and limited data available suggest clinical benefit without a higher toxicity [35,36]. A recent study has demonstrated that high dose INH in MDR patients with inhA mutations has similar magnitude of bactericidal activity as with standard doses in drug-susceptible TB patients [37].…”

Section: Plos Onementioning

confidence: 99%

Isoniazid resistance profile and associated levofloxacin and pyrazinamide resistance in rifampicin resistant and sensitive isolates/from pulmonary and extrapulmonary tuberculosis patients in Pakistan: A laboratory based surveillance study 2015-19

Tahseen

Khanzada²,

Rizvi³

et al. 2020

PLoS ONE

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Background Pakistan is among top five high burden countries for tuberculosis and drug resistant TB. Among rifampicin sensitive new pulmonary TB (PTB), prevalence of isoniazid resistance is 8.3% (95%CI: 7.0-10.7) and resistance to fluoroquinolone is higher (11�1%, 95%CI: 7�8-14�3) than isoniazid resistance. Method Five year retrospective data (2015-2019) of drug susceptibility testing (DST) for Mycobacterium tuberculosis isolates, performed using recommended phenotypic (pDST) and/or genotypic (gDST) methods was analyzed stratified by rifampicin results for isoniazid resistance profiles and associated levofloxacin and pyrazinamide resistance.

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“…A one-dose-fits-all dosing approach must be carefully weighed against the risk of toxicity in patients with slow NAT2 (N-acetyltransferase 2) metabolizer status, whose INH concentrations can be up to threefold higher than those in fast acetylators, and the consequences of potential differences in efficacy related to mutation type. Accumulating indirect evidence that HD-INH has activity against strains with katG mutations (which tend to produce higher minimum inhibitory concentrations in vitro) needs confirmation (3)(4)(5). In the next phase of INHindsight, we will measure the early bactericidal activity of HD-INH (15-20 mg/kg) in patients with pulmonary TB caused by Mycobacterium tuberculosis strains with katG mutations.…”

Section: From the Authorsmentioning

confidence: 99%

Reply to Decroo et al.: High-Dose First-Line Treatment Regimen for Recurrent Rifampicin-Susceptible Tuberculosis

Dooley

Miyahara

Groote-Bidlingmaier

et al. 2020

Am J Respir Crit Care Med

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GenoType MTBDRplus. rpoB mutations outside the 81-bp rifampicin resistance determining region are not covered by these commercial assays. Another, not unusual cause of missed rifampicin resistance is heteroresistance resulting from a mixed population of both susceptible and resistant TB bacilli (3). If patients with resistance to isoniazid and missed rifampicin resistance were treated with the World Health Organization levofloxacin-strengthened first-line regimen, resistance to fluoroquinolone would emerge rapidly. Because the efficacy of second-line TB treatment relies on a fluoroquinolone as a core drug, treatment options would be dramatically reduced. Finally, as shown by Dooley and colleagues, as well as by previous studies (4), high-dose isoniazid may overcome mutations that confer resistance to isoniazid and render normal doses ineffective (4). Excluding isoniazid, which has the highest early bactericidal activity of all first-line drugs, increases the risk of acquiring rifampicin resistance, as mutant bacilli may survive the early phase of TB treatment. Moreover, Boeree and colleagues showed that high-dose rifampicin (35 mg/kg) was safe and reduced time to culture conversion when compared with normal-dose rifampicin (10 mg/kg) (5). Although isoniazid is used for its bactericidal activity against actively replicating bacilli, rifampicin has both a bactericidal effect against rapidly replicating bacilli and a sterilizing effect against dormant bacilli. Both types of action are needed to ensure a relapse-free cure (6). Globally, about 11.6% of patients with recurrent TB have rifampicin-susceptible/isoniazid-resistant TB. Studies should compare high-dose first-line regimens with normal-dose regimens in terms of safety, treatment success, and acquired rifampicin resistance in patients with rifampicin-susceptible/isoniazid-resistant TB. If it is shown to be safe and efficacious, high-dose first-line treatment could be used in all patients with recurrent rifampicin-susceptible TB, regardless of initial isoniazid resistance, thus avoiding delays in retreatment. Such an improved use of first-line anti-TB drugs would have major advantages. No additional susceptibility testing beyond rifampicin testing would be required and there would be no delay between a diagnosis of rifampicin-susceptible recurrent TB and initiation of treatment. If first-line treatment could rely on first-line drugs only, second-line treatment options would be maximally safeguarded. n

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Improved Outcomes With High-dose Isoniazid in Multidrug-resistant Tuberculosis Treatment in Haiti

Cited by 28 publications

References 6 publications

Short-Course Regimen for Multidrug-Resistant Tuberculosis: A Decade of Evidence

Short-Course Regimen for Multidrug-Resistant Tuberculosis: A Decade of Evidence

Isoniazid resistance profile and associated levofloxacin and pyrazinamide resistance in rifampicin resistant and sensitive isolates/from pulmonary and extrapulmonary tuberculosis patients in Pakistan: A laboratory based surveillance study 2015-19

Reply to Decroo et al.: High-Dose First-Line Treatment Regimen for Recurrent Rifampicin-Susceptible Tuberculosis

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