[in Japanese]

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It has been reported that picolinic acid (PA) potentiated the antimicrobial activity of mouse bone marrowderived macrophages (Mφs) against intracellular Mycobacterium avium complex (MAC) and that such PA effects were accompanied by PA-induced Mφ apoptosis. It is of interest to examine whether or not such a phenomenon is also observed for human Mφs. In the present study, we examined PA activity in inducing apoptosis of THP-1 human Mφs (THP-1 Mφs) using the Annexin V and DNA laddering assay methods. Flow cytometric studies on test Mφs stained with Annexin V demonstrated that PA treatment induced phosphatidylserine translocation to the outer leaflet of the cell membrane THP-1 Mφs with or without M. avium infection. On the other hand, PA treatment did not cause significant levels of DNA laddering, even when test THP-1 Mφs were infected with M. avium. These findings suggest that PA may induce the early phase apoptotic events in THP-1 Mφs, without inducing DNA fragmentation characteristic to the middle to late phase apoptosis. Our present results provide insights into the possible role of Mφ apoptosis in the PA-induced potentiation of Mφ anti-MAC anitmicrobial activity.

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In vitro interaction between meropenem (MEPM) and vancomycin (VCM), teicoplanin (TEIC), linezolid (LZD), or arbekacin (ABK) was studied using the checkerboard technique in 207 clinical isolates of methicillin-resistant Staphylococcus aureus (MRSA)(MIC of MEPM≥32). Of 207 strains, synergistic or additive action was observed in all strains by combination of MEPM and VCM or TEIC. A combination of MEPM and LZD or ABK showed synergistic or additive 196 strains (94.7%) and 159 strains (76.8%). Antagonism was not observed in any combination of MEPM and VCM, TEIC, or LZD, but 22 strains (10.6%) exhibited antagonism in combination with MEPM and ABK. It is thus important to know both the susceptibility of anti-MRSA agents alone and the combined effects of agents.

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We evaluated the influence of human albumin (HA) on the in vitro activity of 8 oral beta-lactam antibiotics against 59 recently isolated strains of Streptococcus pneumoniae.
MICs were determined by broth microdilution with Mueller-Hinton broth alone (MHB) or supplemented with 4g/dL human albumin (MHB-alb).
The geometric mean of MICs obtained in MHB-alb of amoxicillin, faropenem (FRPM), cefcapene pivoxil, cefotiam hexetil, cefteram pivoxil (CFTM-PI), cefditoren pivoxil (CDTR-PI), and cefpodoxime proxetil were 022, 0.39, 0.54, 0.86, 0.91, 1.06, and 1.12μg/mL. The MIC ratio (MIC obtained in MHB-alb/MIC obtained in MHB) of FRPM, CDTR-PI, and CFTM-PI were 6.9, 42, and 2.3, and those of other antibiotics less than 2.0. HA had a greater influence on the antibacterial activity of FRPM, CDTR-PI, and CFTM-PI.
Susceptibility ratios of S. pneumoniae for tested antibiotics were calculated using two types of breakpoint (BP) MIC satisfying 40% time above MIC for the dosing interval. BP1 was based on total concentrations of human blood and total concentrations were revised by the coefficient of human serum protein binding rate (FRPM: 05, CDTR-PI: 0.2, CFTM-PI: 0.5, other antibiotics: 1) in BP2.
Susceptibility ratios with all antibiotics using BP1 and MIC with HA were similar to those using BP2 and MIC without HA.
These findings suggest that in the presence of HA, MICs of FRPM, CDTR-PI, and CFTM-PI were markedly increased over those of other antibiotics. Protein binding should therefore be considered in PK/PD BP for beta-lactam antibiotics.

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In northern Kyushu and Yamaguchi, 323 Staphylococcus aureus isolates which MIC of oxacillin was less than 4μg/mL by broth microdilution method were collected in 2005. The susceptibility of isolates was examined using Kirby Bauer disk diffusion test of cefoxitin and MIC determination by agar dilution method. The MIC range of oxacillin against all 323 isolates was ≤0.25-2μg/mL. mecA was detected from 9 (2.8%) of all isolates. In this 9, the inhibitory zone diameter of cefoxitin ranged from 18 to 22 mm. According to Clinical and Laboratory Standards Institute M100-S17, if the zone diameter of the cefoxitin disk is less than 21 mm, the isolate is judged as methicillin-resistant S. aureus (MRSA). Eight of the 9 isolates were judged as MRSA by the cefoxitin disk diffusion test. Among specimens, isolates from skin had mecA most frequently at a ratio of 23.5%(4/17). Regarding patient age, isolates having mecA from patients who were less than 5 years old accounted for 122%(5/41) among patients in the corresponding age group. Seven of the 9 isolates that were mecA-positive and oxacillin-susceptible were outpatients. Since these 7 isolates were divided into 4 groups by Sma I-digested DNA pattern, the result suggested that some clone of mecA-positive and oxacillin-resistant S. aureus may have spread in this area.
Though mecA-positive and oxacillin-susceptible (MIC ≤2μg/mL) isolates were detected 2.8% of all isolates, the ratio was reduced by using cefoxitin disk diffusion test until 0.3%. The frequency of mecA-positive, oxacillin-susceptible, and cefoxitin-susceptible S. aureus isolates is yet very low, but it is important to continue studying its ratio.

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Aspiration pneumonia is a pulmonary disease caused by aspiration of mouth contents as a result of deglutition dysfunction, and the number of patients is, especially among the elder population, on the rise. As for the causative agents of aspiration pneumonia, based on the pathogenetic mechanism described above, oral surgery-related bacterial pathogens, especially anaerobes, are believed to be the major etiologic agents.
In this study, we evaluated the antimicrobial susceptibility pattern of the major causative oral surgeryrelated bacterial pathogens-Streptococcus anginosus group, Peptostreptococcus species, Prevotella species and Fusobacterium species-against antimicrobial agents-piperacillin, tazobactam/piperacillin (TAZ/PIPC), ampicillin, sulbactam/ampicillin (SBT/ABPC), ceftriaxone, cefepime, meropenem (MEPM) and clindamycin. Of these antimicrobial agents, TAZ/PIPC and SBT/ABPC, penicillin antimicrobial agents containing a betalactamase inhibitor, and MEPM showed the highest antibacterial activity against all the four pathogens.
These results suggest that penicillin antimicrobial agents containing a beta-lactamase inhibitor, such as TAZ/PIPC, are effective in treating aspiration pneumonia, which are mainly caused by oral anaerobic bacteria and often associated with oral surgery-related inflammation and odontogenic infections. In addition, these findings lend support to the selection of TAZ/PIPC as empiric therapy for the treatment of aspiration pneumonia in guidelines published overseas.

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