To assess the efficacy of high-dose cefteram pivoxil (CFTM-PI) against respiratory infection in children, we investigated CFTM antibacterial activity against clinical isolates from pediatric patients, its bactericidal effect using an in vitro pharmacokinetic model (IVPM) that simulates the serum concentration of high-dose CFTM. Additionally, antibacterial activity of CFTM against anaerobic bacteria that are dominant in the intestinal bacterial flora of infants was evaluated.

Clinical isolates from pediatric patients between 2012 and 2015 were examined for their susceptibility to cephems and penicillins. The MIC₉₀s against 50 Streptococcus pneumoniae isolates were as follows, 0.5 μg/mL for cefditoren (CDTR), 1 μg/mL for CFTM and cefcapene (CFPN), 2 μg/mL for clavulanic acid/amoxicillin (CVA/AMPC, 1:14), 8 μg/mL for cefdinir (CFDN). The MIC₉₀s against 49 Haemophilus influenzae isolates were as follows, 0.5 μg/mL for CDTR, 1 μg/mL for CFTM, 2 μg/mL for CFPN, 8 μg/mL for CFDN, 16 μg/mL for CVA/AMPC. The MIC₉₀s against 32 Streptococcus pyogenes isolates were as follows, 0.0078 μg/mL for CFTM and CDTR, 0.0156 μg/mL for CFPN, CFDN, and CVA/AMPC. The MIC₅₀s and MIC₉₀s of each antibacterial agent were about the same as those of previous study in Japan.

The IVPM simulating the serum concentrations of the antibacterial agents administered orally at 6 mg/kg three times a day with albumin-supplemented medium, was used to examine the bactericidal effect of CFTM and CDTR against 4 S. pneumoniae isolates from pediatric patients. Both antibacterial agents showed more than 3 log₁₀ reduction in viable cell counts within 6 hours after exposure.

MICs of CFTM against Bacteroides and Bifidobacterium, dominant species in the intestinal bacterial flora of infants, ranged between 1 and 256 μg/mL. This high MIC may be one of the reasons why the incidence of diarrhea in pediatric patients treated with CFTM-PI is lower.

In summary, our findings suggest that high-dose CFTM-PI may be effective for the treatment of children with respiratory infection.

Antibacterial activities of garenoxacin (GRNX) and various oral antibacterial agents against 60 strains of oral streptococci isolated between 2015 and 2016 were measured. MIC₉₀ of GRNX against 30 strains of Streptococcus anginosus group (SAG) was 0.12 μg/mL, being the lowest among antibacterial agents tested, followed by 0.25 μg/mL of moxifloxacin (MFLX), clavulanic acid/amoxicillin (CVA/AMPC) and sultamicillin (SBTPC), 1 μg/mL of levofloxacin (LVFX), and >16 μg/mL of azithromycin (AZM). MIC₉₀ of GRNX against 30 strains of oral streptococci other than SAG was 0.12 μg/mL, being the lowest among antibacterial agents tested, followed by 0.25 μg/mL of MFLX, 1 μg/mL of CVA/AMPC and SBTPC, 2 μg/mL of LVFX, and >16 μg/mL of AZM.

We also assessed the efficacy of quinolones(GRNX, LVFX and MFLX) using the Monte Carlo simulation. The probability of target attainment for free area under the curve (fAUC, f: ratio of protein-unbound) /MIC ratio (fAUC/MIC) was calculated. GRNX, MFLX and LVFX showed a probability of 97.0, 95.9, and 66.9%, respectively, at fAUC/MIC=30 considered target value of efficacy.

In addition, MIC and the mutant prevention concentration (MPC) of various quinolones against 14 strains of the SAG isolated in 2013 were measured. MIC₉₀ and MPC₉₀ of GRNX against these strains were 0.125 and 0.25 μg/mL, respectively, and were lower than those of LVFX and MFLX. GRNX had a narrow mutant selection window (MSW), which is defined as the range between MIC₉₀ and MPC₉₀, compared to LVFX and MFLX. The MPC/MIC ratios of LVFX and MFLX ranged from 1 to 4, but those of GRNX were 1–2.

In conclusion, GRNX showed a high probability of target attainment, the low MPC value and the narrow MSW, suggesting that GRNX is useful against infectious disease caused by oral streptococci in terms of efficacy and resistant prevention.

The action mechanism of daptomycin (DAP0 is different from that of existing antimicrobial agents. So, it is said that the resistance rates of DAP is exceptionally low. On the other hand, there are reports that resistant strain result from prolonged administration of DAP. Hence, using antimicrobial use density (AUD) which is index of usage, days of therapy (DOT) which is index of dosing days and AUD/DOT which is index of daily dose, we researched relationship between consumption of DAP and drug sensitivity from September 2014 to January 2016. And, we measured minimum inhibitory concentration (MIC) for DAP in Gram-positive isolates. As a results, we collected 136 isolates during the study (Enterococcus sp.; 16 strains, Staphylococcus sp.; 120 strains). The coefficients of correlation between AUD, DOT or AUD/DOT of DAP and drug sensitivity were 0.37, 0.23 or 0.44.

The risk factors of resistant isolates are inappropriate use of therapy at low doses or prolonged administration. However, in this study, the consumption of DAP is not associated with resistance rates of Gram-positive isolates. Therefore, we thought that confounding factors other than antimicrobial usage should be considered.

We implemented inter-institutional/professional antimicrobial stewardship (IIPAS) with outcome indices of susceptibility in Pseudomonas aeruginosa strains, antimicrobial use density (AUD) and blood culture density.

Materials were a total of 2,150,827 patient-days in four district hospitals 2012 to 2016. Interprofessional teams conducted IIPAS in those hospitals where 90-percentile minimum inhibitory concentrations (MIC90) in 22 antimicrobials for P. aeruginosa isolates were analyzed at a single laboratory. We obtained AUD and blood culture density defined as (number of test sets/patientdays) ×1,000.

As a result, an average of 44.3% antimicrobials showed decrease of MIC90 for P. aeruginosa over years. The antimicrobial numbers of MIC90 >64 μg/ml and AUD >10 (a 88-percentile integer) were 1 and 1 in Hospital A, 5 and 2 in Hospital B, 3 and 1 in Hospital C, and 14 and 4 in Hospital D, respectively. The blood culture densities increased in 4 hospitals.

Whereas MIC90 was increased in hospitals showing increased antimicrobials with high AUD, IIPAS may have resulted in return of susceptibility in P. aeruginosa strains. This event may have related to increase of blood culture densities.