In an effort to obtain a developmental sequence of mutations in the Rhizobium-legume interaction within a single legume species, we have characterized the early events of nodule development in

An aerosol physics test facility was used in a series of eight experiments to gather an integrated comprehensive broad base of data on the fate of surrogates of microorganisms that cause smallpox, plague, glanders, anthrax, and viral hemorrhagic fevers. The results are directly relevant to the public health issue of how to protect the occupants of buildings against bioterrorism. The test conditions were directly relevant to the indoor air environment situation, and the results can be generalized to buildings that are now occupied. The reductions in concentrations of relevant viruses and bacteria--including gram-negative fermenters and nonfermenters, gram-positive cocci and bacilli, and spores--were substantial and statistically robust. The data show that the bioterrorism-relevant aerosolized viruses and bacteria, including spores, respond like small particulates to the primary (electrical) forces that control the distribution of small particulates in a room. Further, these relevant microorganisms respond like small particulates to means designed to control airborne particulates. The results could be used to anticipate the effects of a bioterrorist attack on the public health, provide information on means that can be used to minimize such effects, and used to make decisions on how best to protect occupants of specific buildings at minimal cost and with assurance of success.

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...

The stabilities of amoxicillin (16 g/ml) and clavulanate (8 g/ml), alone and in combination in BACTEC medium (Middlebrook 7H12B medium), were determined by high-performance liquid chromatography (HPLC) and bioassay. By HPLC, the half-life of amoxicillin (trihydrate and sodium) in combination with clavulanate in nonradiolabelled 7H12B medium was 6.7 days, whereas the half-life of clavulanate in combination with amoxicillin was 2.0 days. By bioassay, the half-lives of amoxicillin trihydrate and clavulanate in radiolabelled 7H12B medium were comparable (7 and 2 days, respectively) to those determined by HPLC. When clavulanate was tested alone, the half-life was determined to be 1.88 days by HPLC and 1.87 days by bioassay. The relatively short half-life of clavulanate can be adjusted by a procedure of ''topping up,'' or adding one-half the concentration of clavulanate every second day, in order to allow accurate amoxicillin-clavulanate MIC testing with the BACTEC mycobacterial susceptibility system.

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