Patients with nursing and health care-associated pneumonia (NHCAP) include those at risk for aspiration or those who have difficulties to take pills. We conducted a prospective study to examine the efficacy and safety of moxifloxacin (MFLX) administration through an enteral feeding tube by a simple suspension method in patients with NHCAP receiving long-term care at the hospital.

The study was performed in subjects meeting the definition of NHCAP according to the Japanese Respiratory Society amongst patients with pneumonia who were fed by a feeding tube under long-term care at Makita General Hospital during the period from Dec. 2010 to Oct. 2011. A dose of 400mg MFLX was administered once daily for three consecutive days, as a rule, through a gastrostomy or nasogastric feeding tube by a simple suspension method. The primary endpoint was a test of cure (TOC) 7 days after the last administration.

Sixteen patients were included in the analysis of the study. As the patient background, 11 were assessed as long-term care level 5, 5 were not receiving care, and the Eastern Cooperative Oncology Group Performance Status (ECOG-PS) score was 4 in all patients. Twelve (75%) had experience of aspiration while 4 (25%) had none, and all had some underlying diseases (complications). The severity of pneumonia according to the A-DROP scoring system was mild in 1 patient (6%), moderate in 14 patients (88%) and severe in 1 patient (6%).

A test of cure 7 days after the last administration, which was the primary endpoint, showed an efficacy rate of 81.3% (13/16 patients), while the efficacy evaluation 3 days after administration, which was an endpoint for early phase drug efficacy, showed that the drug was effective in all patients (100%; 16/16 patients). Neither adverse drug reactions nor abnormal laboratory findings were observed.

MFLX administration through an enteral feeding tube by a simple suspension method was shown to be as highly effective as injection in patients with NHCAP having eating and swallowing disorders, indicating its potential to become an alternative option to conventional intravenous injection therapy.

The growing number of infection caused by extended-spectrum 𝛽-lactamase (ESBL) producing pathogens has prompted a more rational use of available antibiotics because of the paucity of new, effective agents. Flomoxef (FMOX) is one of the 𝛽-lactam antibiotic which is stable against 𝛽-lactamase. In this study, the antibacterial activity of FMOX was investigated, and Monte Carlo Simulation was conducted to determine the appropriate dosing regimens of FMOX based on the probability of target attainment (TA%) at the critical drug exposure metric of time that drug concentrations remain above 40% (showing bacteriostatic effect) or 70% (showing bactericidal effect) of time during which plasma concentration above minimum inhibitory concentration (MIC) of the drug (T_>MIC) against the ESBL producing Enterobacteriaceae. The effective regimens to achieve 80% of TA% at 70% of T_>MIC were 1g every 8 hours with 2–4 hours infusion, and 1g every 6 hours with 1–4 hours infusion. Moreover, all the tested regimens were effective to achieve 80% of TA% at 40% of T_>MIC. These results of pharmacokinetics/pharmacodynamics (PK/PD) modeling showed the potential efficacy of FMOX against bacterial infections caused by ESBL producing Enterobacteriaceae.

This study was performed to elucidate the relationship between antimicrobial use density (AUD) and Clostridium difficile infection (CDI) manifesting as antimicrobial-associated diarrhea (AAD) in hospital wards during a 4-year period. Case definition of CDI was adult exhibiting AAD with a daily stool frequency of three or more, arising at least 48 hours after ward admission, and fecal samples testing positive for toxin (A and/or B). Metronidazole or vancomycin was orally administered as treatment. AUDs were calculated for a total of 21 antimicrobials in a span of 48 months and nine wards. We included the average value of AUDs, representing two succeeding months of sample submission into the sample information. We also entered data on the 2-year division and intensified contact precaution for statistical analysis. Of a total of 463 cases, 95 (20.5%) were CDI-positive. Multivariate regression analysis showed odds ratios [OR] of 1.739 (95% confidence interval [C1] of 1.050 ～ 2.881, P=0.032) and 1.598 (95% CI of 1.006 ～ 2.539, P=0.047) for clindamycin and piperacillin, respectively in AUD. Thus increased ward AUDs of clindamycin and piperacillin may run the risk of CDI.

We assessed the safety and pharmacokinetics of arbekacin sulfate (ABK, brand name: Habekacin^® injection) in single and 7-day multiple administration of ABK 400 and 600mg as potency to healthy male volunteers.

In the single administration of ABK 400 and 600mg (over 30 min, drip infusion), C_max values were 41.0±3.6𝜇g/mL and 63.0±9.9𝜇g/mL, respectively. Serum ABK concentrations at 60 min (C_peak) after the start of administration were 23.2±2.9𝜇g/mL and 38.5±3.3𝜇g/mL, respectively, and the mean serum ABK concentrations at 24 hr (C_trough) after the start of administration were less than 0.4𝜇g/mL( LOQ: limited of quantitation). C_max, C_peak and AUC_0–∞ were increased with doses, and t_1/2, CL_tot, CL_r V_ss and urinary excretion were comparable at both doses.

In the multiple administration of ABK 400 and 600mg (over 30 min, drip infusion) once a day for 7 days, C_max, C_peak and AUC_0–∞ were comparable from the 1^st day through to 7th day and increased with doses. After the administration, the serum ABK concentrations were decreased with time, and the means of C_trough were 0.4𝜇g/mL (LOQ)–0.5𝜇g/mL, which showed ABK has no tendency toward accumulation. In addition, t_1/2, CL_tot, CL_r Vss and urinary excretion were constant throughout administration days at either dose, and CL_tot containing CL_r was not decreased. There were no notable changes in the functions of the kidney, auditory organs, etc.

Based on the above-mentioned results, when ABK 400 or 600mg was intravenously administered over 30 min once or once a day for 7 days to the healthy male volunteers with normal renal clearance, it is suggested there were no problems in terms of safety, and C_max were 36.7–54.1 and 44.2–78.5𝜇g/mL, respectively. In addition, C_trough was 0.5𝜇g/mL or lower at either doses and ABK was not accumulated in multiple administration of ABK. ABK was, therefore, expected to have good safety profile and favorable pharmacokinetics.