Is there a place for  -lactams in the treatment of multidrug-resistant/extensively drug-resistant tuberculosis? Synergy between meropenem and amoxicillin/clavulanate

• Published in: Journal of antimicrobial chemotherapy Vol. 68; no. 2; pp. 366 - 369
• Main Authors: Gonzalo, Ximena, Drobniewski, Francis
• Format: Journal Article
• Language: English
• Published: Oxford Oxford Publishing Limited (England) 01.02.2013
• Subjects: Amoxicillin; Antibiotics; Bacteriology; Drug development; Drug resistance; Drug therapy; Meropenem; Minimum inhibitory concentration; Mycobacterium tuberculosis; Tuberculosis
• ISSN: 0305-7453; 1460-2091
• DOI: 10.1093/jac/dks395

To: (i) assess if amoxicillin/clavulanate is a useful option for the management of multidrug-resistant/extensively drug-resistant tuberculosis (MDR/XDR-TB); (ii) assess if meropenem/clavulanate is active against Mycobacterium tuberculosis at concentrations achievable in vivo; and (iii) determine whether there was inhibition of meropenem/clavulanate activity in the presence of amoxicillin. Twenty-eight M. tuberculosis strains (7 susceptible, 2 monoresistant, 16 MDR and 3 XDR) were included in the study and tested against different concentrations of meropenem, meropenem/clavulanate, amoxicillin/meropenem, amoxicillin/clavulanate and amoxicillin/meropenem/clavulanate using the Bactec 960 MGIT® system. All 28 strains were resistant to meropenem at the highest concentration tested (5 mg/L). Although 24 strains were susceptible to amoxicillin/clavulanate, 7 strains were susceptible only to 7.2/2.5 mg/L amoxicillin/clavulanate, 10 strains were susceptible to 3.6/2.5 mg/L amoxicillin/clavulanate, 6 strains were susceptible to 1.8/2.5 mg/L amoxicillin/clavulanate and 1 strain was susceptible to 0.9/2.5 mg/L amoxicillin/clavulanate. Therefore, 4/28 strains (14.29%) were resistant to the highest concentration of amoxicillin tested (7.2 mg/L); all of them were MDR. All of the 11 strains resistant to amoxicillin or susceptible only to 7.2 mg/L amoxicillin increased their susceptibility to amoxicillin/clavulanate after the addition of meropenem. The addition of clavulanate to meropenem reduced the MIC of meropenem by an average of over 1.8 dilutions. The combination of amoxicillin/clavulanate plus meropenem is active against MDR/XDR-TB in vitro, and this triple therapy could be a useful therapy for MDR/XDR-TB and possibly help to reduce the development of further resistance. The drug susceptibility technique used here is routinely used, with modification, in mycobacteriology laboratories.