There are a limited number of reports that compare the clinical efficacy of anti- MRSA agents such as arbekacin (ABK), vancomycin (VCM), teicoplanin (TEIC) and linezolid (LZD). There is a tendency for these four agents to show variation in the inflammatory response parameters, in C-reactive protein (CRP) and in white blood cell count (WBC), depending on the administration period. There was no significant difference among the agents in analysis of variance (ANOVA) in the group of days 1–3 (p=0.0536) but there was some significant difference in the group of days 4–7, as well as days 8–14 (p<0.001, p<0.01) in relative variation rate of CRP. Furthermore, we compared in more detail the groups of LZD, VCM and ABK, with a significant decrease of CRP, each of which showed more decrease in comparison with the group of TEIC in the period days 4–7 (p<0.01). We took 1-hr serum level after days 3–4, with the ABK treatment as the peak concentration (Cpeak). Having made nonlinear logistic regression analysis of CRP and Cpeak/MIC, we concluded that the decrease rate estimable by early inflammatory effect could be decreased to some 40%, assuming that Cpeak/MIC shows the high value within 4 days after ABK treatment.

The effectiveness of continuous regional arterial infusion therapy using protease inhibitors and antibiotics for severe acute pancreatitis has been previously reported. Carbapenem antibiotics, which have a broad antibacterial spectrum, and nafamostat mesilate are often used for this therapeutic approach. We investigated the compatibility of various carbapenem antibiotics with nafamostat mesilate.

Carbapenem antibiotics were dissolved in 30 mL of saline or 5% glucose and the appearance, pH, and stability of the solutions were determined. The changes in each carbapenem antibiotic solution after mixing with nafamostat mesilate were then investigated.

Biapenem and doripenem showed a residual rate of ≥90% at 8 hours after dissolution in saline or 5% glucose and exhibited an appropriate appearance and residual rate (≥90%). After mixing with nafamostat mesilate, biapenem maintained a residual rate of ≥90% for the longest time period (8 hours) and exhibited a slight coloration, followed by doripenem (6 hours) and meropenem dissolved in saline. The other carbapenem antibiotics that were tested exhibited changes in appearance or their residual rate.

Biapenem and doripenem, which exert their effects in a time-dependent manner, can be infused for prolonged periods for the treatment of not only severe acute pancreatitis, but also other severe infections.

Doripenem (DRPM) is one of the carbapenems which has a broad-spectrum and strong activity against Pseudomonas aeruginosa. This observational study was conducted between April 2006 and March 2007 in Japan to evaluate the efficacy and safety of DRPM 0.5 g three times a day for sepsis with neutropenia in patients with hematologic diseases. One hundred-nineteen patients were enrolled from 34 medical institutes, comprising 117 patients for safety evaluation and 104 for efficacy evaluation. Monotherapy of DRPM 0.5 g three times a day (DRPM monotherapy) was evaluated in 73 patients. The response rates of DRPM monotherapy at 72 hours and at Day 7 were 31.5% (23/73) and 67.1% (49/73), respectively. The incidence of adverse reactions including abnormal changes in laboratory values was 23.1%, and hepatic toxicity was most common. All of these adverse events were judged by the investigators as non-serious and tolerable. These results suggest that DRPM is useful for sepsis with neutropenia, though further study may be warranted.

We examined the peck concentration (Cmax)/minimal inhibitory concentration (MIC) and the clinical efficacy in methicillin-resistant Staphylococcus aureus(MRSA) pneumonia and Gram-positive cocci bacteremia. We evaluated arbekacin (ABK) on 22 cases of pneumonia and 10 cases of bacteremia in Aichi Medical University Hospital between August 2008 and July 2011, retrospectively.

In pneumonia cases, Cmax/MIC was 16.4±2.8 in the effective group, and was 17.6±4.5 in the not effective group, the significant differences were not accepted (p=0.8). The dosage of ABK was 4.7±1.4 mg/kg/dose in the effective group and was 4.3±0.7 mg/kg/dose in the not effective group.

In bacteremia cases, Cmax/MIC was 24.2±13.9 in the effective group and 12.9±3.9 in the not effective group about clinical efficacy, and the high tendency was accepted by the effective group (p<0.05). The dosage of ABK was 3.4±1.1 mg/kg/dose in the effective group, and 3.0± 0.6 mg/kg/dose in the not effective group.

In this examination, the significant difference was not observed in clinical efficacy and Cmax/MIC in the pneumonia cases. Although it was reported that clinical efficacy of ABK was given Cmax/MIC at eight or more, in this examination, all cases was eight or more at Cmax/MIC, and the clinical effect was 40.9%.

On Cmax/MIC of ABK, clinical effective group was higher than not effective group in bacteremia cases, it was suggested that the administration design should make that Cmax/MIC at least about 14 or more would be necessary.

Efficacy, safety and pharmacokinetics of meropenem (MEPM) were assessed when 1 g (40 mg/kg for some of the pediatric patients) t.i.d. was administered every 8 hours to 101 adult and 6 pediatric patients with febrile neutropenia (FN) as diagnosed based on the Japanese guideline for FN treatment.

The efficacy rate evaluated as antifebrile effect up to Day 4 of treatment was 40.0% (40/100) in adult and 66.7% (4/6) in pediatric patients. The antifebrile effect in adult patients was analyzed after stratifying them according to their neutrophil counts up to Day 4. Treatment with MEPM produced an antifebrile effect not only in patients with higher neutrophil counts (≥500/mm³) but also in those with lower counts (<100/mm³), and the efficacy rate was comparable between the two groups: 38.2% in the<100/mm³ group and 29.4 to 55.6% in the≥500/mm³ group.

The bacteriological efficacy of MEPM evaluated as disappearance rate on Days 3 to 5 and Day 7 was both 100% (8/8 and 4/4, respectively). The time above minimal inhibitory concentration (%T>MIC) in the treatment interval was greater than 90% in 9 out of 10 patients for whom likely causative organism was isolated and identified after MEPM treatment or for whom causative organism emerging after treatment was isolated and identified.

The incidence of adverse events was 93.1% in adult and 83.3% in pediatric patients. There were three deaths and one serious adverse event reported among the adult patients; however, all these cases were assessed as not related to the study medication. The incidence of adverse drug reactions was 45.5% and 66.7%, respectively. All the observed adverse drug reactions were mild or moderate in severity and none of them was severe. Adverse drug reactions which were unknown from the previous MEPM clinical studies and investigation of the results of clinical experience include ｀chest discomfort’, ｀blood uric acid decreased’, ｀lymphocyte deformation’, ｀blood uric acid increased’, ｀abnormal funduscopy’, ｀hypesthesia’ and ｀hemorrhagic cystitis’. All these events were mild or moderate in severity and resolved without requiring any action or after providing symptomatic treatment. There was no unknown adverse drug reaction that resulted in treatment discontinuation. No nervous system disorders such as convulsion and impaired consciousness were reported.

The results show that monotherapy of MEPM 1 g (or 40 mg/kg for some of the pediatric patients) t.i.d. every 8 hours was effective, and was also safe and well tolerated in adult and pediatric patients with FN. Therefore, MEPM monotherapy is expected to be useful as the initial treatment for Japanese patients with FN.