In vitro susceptibility of Mycobacterium fortuitum to amoxicillin or cephalothin in combination with clavulanic acid

230

103

Broth microdilution MICs were determined for 258 clinical isolates of Mycobacterium fortuitum (3 biovariants) and M. chelonae (2 subspecies) with amikacin, tobramycin, cefoxitin, doxycycline, erythromycin, and sulfamethoxazole-trimethoprim and with several new jI-lactams and aminoglycosides and ciprofloxacin. Variations in susceptibility by and within species subgroups confirm the need for susceptibility testing against clinically important strains.The role of the rapidly growing mycobacteria Mycobacterium fortuitum and M. chelonae (formerly M. chelonei) as agents of human disease has been clearly established (22). Except for the aminoglycosides, these organisms are resistant to the antituberculosis agents, and testing against these drugs is no longer indicated (19). However, they are susceptible to some drugs not routinely tested in laboratories specializing in mycobacteriology; these agents have been shown to be effective in the treatment of human disease (8, 9, 19, 21a). Because the susceptibilities of M. fortuitum and M. chelonae to these agents varies, testing clinically important strains as an aid in determining a therapeutic regimen is important. Although the need to identify organisms of the M. fortuitum complex to subspecies and even species level remains controversial (11,17), previous studies have suggested that patterns of susceptibility may relate in part to differences between species, subspecies, and biovariants (17,19,20,21,23,24).Between 1978 and 1982, more than 250 strains of rapidly growing mycobacteria were received in our laboratories for identification and susceptibility testing. In this report, we present the antimicrobial susceptibilities of organisms that were identified to the subspecies or subgroup level as determined by a broth microdilution method. Our results provide susceptibility data on a large number of organisms and confirm the need to determine the susceptibilities of M. fortuitum and M. chelonae. In addition, the results show that each species subgroup has a fairly typical pattern of susceptibility.MATERIALS AND METHODS Ot-ganisms. Isolates were submitted to our laboratories for either identification or antimicrobial susceptibility determination, or both. Organisms were identified by standard methods (17), except that the unnamed third biovariant of M. fortuitum was expanded to a complex which includes isolates positive for two or more carbohydrates (mannitol, inositol, or citrate). The strains and number included were M. fortuitum biovariant fortuitum, 98; M. fortuitum biovariant peregrinum, 8; M. fortuitum third biovariant complex, 19; M. chelonae subsp. abscessus, 99; and M. chelonae subsp. chelonae, 34. A small number of these strains were included in our previous study (19). Isolates of the M. chelonae-like * Corresponding author. group were not included in this report because results with most of these strains were reported earlier (9). Aspects of clinical disease and results of therapy for many of these isolates have been reported (8, 9, 21a, 22).The organisms were st...

Section: Discussionmentioning

confidence: 99%

Antimicrobial susceptibility of five subgroups of Mycobacterium fortuitum and Mycobacterium chelonae

Swenson¹,

Wallace²,

Silcox³

et al. 1985

230

103

“…␤-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).…”

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

“…␤-Lactamase production by mycobacteria is likely to be an important factor in the expression of resistance to ␤-lactam antibiotics (11, 12). Indeed, ␤-lactams in combination with either clavulanic acid or other ␤-lactamase inhibitors have in vitro activity against mycobacteria not observed with either agent alone (5,7,8,31).Amoxicillin-clavulanic acid in combination with antimycobacterial agents has been used successfully to treat two patients with multiple-drug-resistant M. tuberculosis infections (18). Preliminary data demonstrate that amoxicillin-clavulanic acid MICs for M. tuberculosis obtained with the BACTEC system were 8/4 or 16/8 g/ml (17), and for 20 M. avium complex isolates screened, MICs were Յ 8/4 g/ml for 10 isolates, and MICs were Յ 4/2 g/ml for 8 isolates (28).…”

mentioning

confidence: 99%

See 1 more Smart Citation

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

Utrup

Moore

Actor

et al. 1995

Neither amoxicillin nor clavulanic acid used alone was active at the highest level tested, i.e., 256.0 g/ml, in vitro against 24 isolates of Mycobacterium fortuitum, Mycobacterium kansasii, and Mycobacterium marinum. However, the MIC of an amoxicillin-clavulanic acid combination of 2:1 was <8.0/4.0 g/ml for 50 percent of the isolates tested, with all isolates being inhibited in the range of 4.0/2.0 to 32.0/16.0 g/ml, respectively. Titration of amoxicillin-clavulanic acid with a fixed 2-g/ml concentration of ethambutol resulted in synergistic activity against 3 of 9 isolates of M. fortuitum, 10 of 10 isolates of M. kansasii, and 5 of 5 isolates of M. marinum. This observation was confirmed in a checkerboard analysis in which fractional inhibitory concentrations were <0.5 for 20 of the 24 isolates. Synergistic activity was observed against the other four isolates in one of two trials. On the other hand, titration of amoxicillin-clavulanic acid in the presence of either one or two fixed concentrations of isoniazid, rifampin, cycloserine, tetracycline, or amikacin failed to result in synergism.There has been a resurgence of mycobacterial infections in the United States mainly attributed to the spread of AIDS in large metropolitan areas (4). A significant number of the mycobacterial isolates causing disease are nontuberculosis mycobacteria (NTM) (29,32). Of these organisms, Mycobacterium avium complex, which represents more than 60% of the NTM isolates, is by far the most common cause of opportunistic NTM infection in patients with AIDS (23, 32). Among other NTM isolates capable of causing infection are M. fortuitum complex (19%) and M. kansasii (10%), with the remaining 10% being other mycobacterial species (13,21). In addition to disseminated infections in patients with AIDS, NTM cause pulmonary, postoperative, soft tissue, and bone and joint infections (29,30).NTM tend to be resistant to a wide variety of antimicrobial agents including many of the ␤-lactam antibiotics (2). Resistance to ␤-lactam antibiotics has been attributed to an interplay between ␤-lactamase activity and cell permeability as well as a low affinity to penicillin-binding proteins (12,15). ␤-Lactamase production by mycobacteria is likely to be an important factor in the expression of resistance to ␤-lactam antibiotics (11, 12). Indeed, ␤-lactams in combination with either clavulanic acid or other ␤-lactamase inhibitors have in vitro activity against mycobacteria not observed with either agent alone (5,7,8,31).Amoxicillin-clavulanic acid in combination with antimycobacterial agents has been used successfully to treat two patients with multiple-drug-resistant M. tuberculosis infections (18). Preliminary data demonstrate that amoxicillin-clavulanic acid MICs for M. tuberculosis obtained with the BACTEC system were 8/4 or 16/8 g/ml (17), and for 20 M. avium complex isolates screened, MICs were Յ 8/4 g/ml for 10 isolates, and MICs were Յ 4/2 g/ml for 8 isolates (28).Since antimycobacterial agents are usually used in combination for the treatment of my...

“…CA is a compound produced by Streptomyces clavuligerus that produces a progressive inhibition of the beta-lactamases, having already been proven effective against the beta-lactamase of the mycobacteria by Cynamon and Palmer (5,6) and by us with amoxicillin (3). After administration by the oral route to humans of 250 mg of CA, a concentration of 5.2 ji,g/ml is found in serum (9).…”

mentioning

confidence: 99%

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

Casal¹,

Rodriguez²,

Luna³

et al. 1987

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.