In vitro susceptibility of Mycobacterium tuberculosis, Mycobacterium africanum, Mycobacterium bovis, Mycobacterium avium, Mycobacterium fortuitum, and Mycobacterium chelonae to ticarcillin in combination with clavulanic acid

Abstract

The in vitro susceptibility of.Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium africanum, Mycobacterium avium, Mycobacterium fortuitum, and Mycobacterium chelonae (M. chelonei) to ticarcillin in combination with clavulanic acid (CA) was studied by the agar dilution method. All the M. tuberculosis, M. bovis, and M. africanum strains were inhibited at a ticarcillin concentration of 32 ,ug/ml or lower in combination with 5 ,ug of CA. M. chelonae and M. avium strains proved resistant to more than 128 ,ug of ticarcillin plus S ,ug of CA per ml. M. fortuitum strains needed 128 ,ug of ticarcillin plus 5 ,Ig of CA to inhibit approximately 30% of the isolates.Ticarcillin is a semisynthetic penicillin of the carboxypenicillin group with a broad antimicrobial spectrum. Its activity against gram-positive and gram-negative bacteria is bactericidal, inhibiting the synthesis of the cell wall by hindering the formation of alanine-glycine unions of polymers of the peptidoglycans (2, 10, 11).Ticarcillin is inactivated by penicillinases but proves stable against the cephalosporinases. It has been proved synergic with the aminoglycosides against gram-positive and gram-negative bacteria, and its association with clavulanic acid (CA) has also been proved highly useful. This has been shown in many in vitro and in vivo studies with different types of microorganisms (7,8).Until now, its activity against mnycobacteria has not been studied.In this study, an in vitro investigation was done of the activity of ticarcillin in association with CA against Mycobacterium tuberculosis, Mycobacterium bovis, Mycobacterium inoculated with a Steer replicator with a 1/100 inoculum of the seed suspension in distilled water. The results were read after 2 weeks of incubation at 37°C.The method used to determine MICs for M. fortuitum and M. chelonae was described elsewhere (4). Cultures of the two species were incubated at 37 and 28°C, respectively, for 7 days in Dubos Oleic Agar Base (Difco Laboratories, Detroit, Mich.). Seed suspensions of the cultures were prepared by dilution with distilled water with the organisms scraped off the plate to match a final opacity of a 1 McFarland standard. An inoculum of the seed suspensions diluted 1:1,000 was delivered to Mueller-Hinton agar plates by using a Steer replicator. The antimicrobial concentrations ranged from 0.25 to 128 jig/ml. The results were read after incubation for 2 to 5 days at 37 and 28°C. The MIC was defined as the lowest concentration of antibiotic that completely inhibited visible bacterial growth. M. tuberculosis H37RV was used as the quality control for media without drugs. Staphylococcus aureus ATCC 25923 (Difco) and Escherichia coli ATCC 25922 (Difco) were used as controls for the MIC and diffusion methods. S. aureus 48, betalactamase producing, resistant to ticarcillin, and susceptible to ticarcillin plus CA, was used.The plates with CA were prepared the day that they were used.

Genome scale portrait of cAMP-receptor protein (CRP) regulons in mycobacteria points to their role in pathogenesis

“…The beta-lactam class of antibiotics has not been used in the treatment of M.tb or other mycobacterial infections as mycobacteria are resistant to these antibiotics and produce betalactamases (Kasik, 1979;Kwon et al, 1995). However, the effectiveness of beta-lactam/beta-lactamase inhibitor combinations has been shown in-vitro for M.tb (Chambers et al, 1995), and also in clinical settings of TB (Chambers et al, 1998;Cynamon et al, 1983;Segura et al, 1998;Sorg and Cynamon, 1987), M. avium (Casal et al, 1987), and M. smegmatis (Yabu et al, 1985). Rv0908 (ctpE), which codes for putative cation transporter, is also present in the same operon.…”

Susceptibilities of nontuberculosis mycobacterial species to amoxicillin-clavulanic acid alone and in combination with antimycobacterial agents

“…␤-Lactamases have been described for most isolates of pathogenic mycobacteria with the exception of members of the M. avium complex (1, 16, 19, 33). Use of the combination of ␤-lactam antibiotics with various ␤-lactamase inhibitors has been shown to be synergistic against a number of mycobacterial species (3,6,7,27).…”

The Mycobacterium avium complex

“…Dapsone (164, 177) and sulfamethoxazole (168) have minimal antimycobacterial activity in vitro and may contribute to reductions in mycobacteremia in certain patients. In addition, there has been renewed interest in the minimal antimycobacterial activity seen with some beta-lactam antibiotics (78,117,360,491).…”