Clinical use of the meropenem-clavulanate combination for extensively drug-resistant tuberculosis [Case study]

Payen, M C; Wit, Stéphane De; Martin, Charlotte; Sergysels, Roger; Muylle, Inge; Laethem, Y. Van; Clumeck, Nathan

doi:10.5588/ijtld.11.0414

Cited by 94 publications

(88 citation statements)

References 9 publications

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“…␤-Lactam-␤-lactamase inhibitor combinations attract more attention due to their effective in vivo and in vitro activity against MDR-TB strains (9,15,16). The present study showed that different ␤-lactam-␤-lactamase inhibitor combinations vary in their anti-MDR-TB efficiency in vitro.…”

Section: Discussionmentioning

confidence: 56%

“…Recently, another ␤-lactam-␤-lactamase inhibitor combination, meropenem-clavulanate, also showed high antimycobacterial activity in vivo against MDR-TB and XDR-TB strains of M. tuberculosis (16). Several clinical trials have provided preliminary evidence of the effectiveness and safety of meropenem-clavulanate in the treatment of MDR-TB and XDR-TB (16,17).…”

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confidence: 99%

“…Several clinical trials have provided preliminary evidence of the effectiveness and safety of meropenem-clavulanate in the treatment of MDR-TB and XDR-TB (16,17). The promising bactericidal activity of the meropenem-clavulanate combination suggests that other ␤-lactam-␤-lactamase inhibitor combinations are suitable for the clinical management of MDR-TB and XDR-TB patients.…”

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confidence: 99%

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In Vitro Activity of β-Lactams in Combination with β-Lactamase Inhibitors against Multidrug-Resistant Mycobacterium tuberculosis Isolates

Zhang

Wang

et al. 2016

Antimicrob Agents Chemother

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The combination of ␤-lactams and ␤-lactamase inhibitors has been shown to have potent in vitro activity against multidrugresistant tuberculosis (MDR-TB) isolates. In order to identify the most potent ␤-lactam-␤-lactamase inhibitor combination against MDR-TB, we selected nine ␤-lactams and three ␤-lactamase inhibitors, which belong to different subgroups. A total of 121 MDR-TB strains were included in this study. Out of the ␤-lactams used herein, biapenem was the most effective against MDR-TB and had an MIC 50 value of 8 g/ml. However, after the addition of clavulanate or sulbactam, meropenem exhibited the most potent anti-MDR-TB activity with an MIC 50 value of 4 g/ml. For meropenem, 76 (62.8%), 41 (33.9%), and 22 (18.2%) of the 121 MDR-TB strains were subjected to a synergistic effect when the drug was combined with sulbactam, tazobactam, or clavulanate, respectively. Further statistical analysis revealed that significantly more strains experienced a synergistic effect when exposed to the combination of meropenem with sulbactam than when exposed to meropenem in combination with tazobactam or clavulanate, respectively (P < 0.01). In addition, a total of 10.7% (13/121) of isolates harbored mutations in the blaC gene, with two different nucleotide substitutions: AGT333AGG and ATC786ATT. For the strains with a Ser111Arg substitution in BlaC, a better synergistic effect was observed in the meropenem-clavulanate and in the amoxicillin-clavulanate combinations than that in a synonymous single nucleotide polymorphism (SNP) group. In conclusion, our findings demonstrate that the combination of meropenem and sulbactam shows the most potent activity against MDR-TB isolates. In addition, the Ser111Arg substitution of BlaC may be associated with an increased susceptibility of MDR-TB isolates to meropenem and amoxicillin in the presence of clavulanate.

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Section: Discussionmentioning

confidence: 56%

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confidence: 99%

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confidence: 99%

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In Vitro Activity of β-Lactams in Combination with β-Lactamase Inhibitors against Multidrug-Resistant Mycobacterium tuberculosis Isolates

Zhang

Wang

et al. 2016

Antimicrob Agents Chemother

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“…In fact, although the experience is still very limited, this carbapenem/clavulanate combination seems to be helpful in the treatment of XDR-TB patients [57][58][59]. In a study by DE LORENZO et al [57], patients treated with meropenem/clavulanate in addition to a linezolid-containing MDR-TB regimen achieved a higher smear conversion rate at 3 months than controls (87.5% versus 56%, p=0.02).…”

Section: Groupmentioning

confidence: 99%

Classification of antituberculosis drugs: a new proposal based on the most recent evidence

Caminero

Scardigli

2015

Eur Respir J

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@ERSpublicationsThe classification of the anti-TB drugs should probably be modified to optimise the use old and new compounds http://ow.ly/QbDSP Multidrug-resistant (MDR) tuberculosis (TB) (resistance to at least isoniazid and rifampicin), with >480 000 cases in 2013, 10% of them being affected by extensively drug-resistant (XDR)-TB (MDR-TB with additional resistance to any fluoroquinolone, and to injectable second-line drugs (SLDs) (capreomycin, kanamycin or amikacin)), continues to represent a real threat to TB control [1][2][3][4]. In some high MDR-TB burden countries, the prevalence of MDR-TB among new cases exceeds 20% and among retreatment cases, reaches almost 50% [1,5].Prevention and quality diagnosis and treatment of MDR-and XDR-TB are part of the crucial interventions included in Pillar 1 of the new World Health Organization (WHO) End TB Strategy, which is focussed on the goal of TB elimination [6][7][8]. Unfortunately, the outcomes of these cases are suboptimal, with 60% success among MDR-TB cases [2], 40% among XDR-TB cases [3] and <20% among the cases with resistance patterns beyond XDR-TB [4]. This means not only high mortality but also significant human suffering and transmission of the Mycobacterium tuberculosis strains within the community [9]. Unfortunately, at present, the treatment of MDR/XDR-TB is still very long, toxic and expensive [10,11].The original WHO guidance on the management of MDR-TB was issued in 1996 [12] and since then, several updated guidelines have been published. The fundamentals on MDR/XDR-TB treatment were published in the 2006 and 2008 WHO guidelines [13,14], where the basic rationale to design therapeutic regimens for these cases was described. According to these recommendations, which are currently followed worldwide, the anti-TB drugs are classified into five main groups indirectly considering the evidence available, the safety and/or the effectiveness of the different drugs. These groups start from the most effective drugs (group 1), grouping the other drugs progressively according to decreasing order of efficacy [15].In the 2011 revision of the WHO MDR/XDR-TB guidelines [16], the composition of different groups of anti-TB drugs was not modified. Therefore, since 2006, the rationale of the classification of the anti-TB drugs has not been changed but several studies have examined the effectiveness, efficacy and safety of the group 5 drugs, and some of these drugs appear to be more effective and well tolerated than others that currently have "higher" ranking in the classification. Furthermore, promising new drugs active against M. tuberculosis have been discovered in the last couple of years [17][18][19][20] and have become progressively available in many parts of the world to treat MDR/XDR-TB.

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“…Carbapenems have been demonstrated to have modest activity in mouse models of TB (14)(15)(16), which are often problematic due to the sensitivity of carbapenems to degradation by murine dehydropeptidase (17). More importantly, encouraging results have been obtained in case series of XDR-TB patients treated with a combination of meropenem plus clavulanate (18)(19)(20).…”

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confidence: 99%

Rapid Cytolysis of Mycobacterium tuberculosis by Faropenem, an Orally Bioavailable β-Lactam Antibiotic

Dhar

Dubée

Ballell

et al. 2015

Antimicrob Agents Chemother

129

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Recent clinical studies indicate that meropenem, a ␤-lactam antibiotic, is a promising candidate for therapy of drug-resistant tuberculosis. However, meropenem is chemically unstable, requires frequent intravenous injection, and must be combined with a ␤-lactamase inhibitor (clavulanate) for optimal activity. Here, we report that faropenem, a stable and orally bioavailable ␤-lactam, efficiently kills Mycobacterium tuberculosis even in the absence of clavulanate. The target enzymes, L,D-transpeptidases, were inactivated 6-to 22-fold more efficiently by faropenem than by meropenem. Using a real-time assay based on quantitative time-lapse microscopy and microfluidics, we demonstrate the superiority of faropenem to the frontline antituberculosis drug isoniazid in its ability to induce the rapid cytolysis of single cells. Faropenem also showed superior activity against a cryptic subpopulation of nongrowing but metabolically active cells, which may correspond to the viable but nonculturable forms believed to be responsible for relapses following prolonged chemotherapy. These results identify faropenem to be a potential candidate for alternative therapy of drug-resistant tuberculosis.

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Clinical use of the meropenem-clavulanate combination for extensively drug-resistant tuberculosis [Case study]

Cited by 94 publications

References 9 publications

In Vitro Activity of β-Lactams in Combination with β-Lactamase Inhibitors against Multidrug-Resistant Mycobacterium tuberculosis Isolates

In Vitro Activity of β-Lactams in Combination with β-Lactamase Inhibitors against Multidrug-Resistant Mycobacterium tuberculosis Isolates

Classification of antituberculosis drugs: a new proposal based on the most recent evidence

Rapid Cytolysis of Mycobacterium tuberculosis by Faropenem, an Orally Bioavailable β-Lactam Antibiotic

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