Onychomycosis that affects the fingernails and, more frequently, the toenails, is caused by infection with fungi, mainly dermatophytes. Owing to its high prevalence in Japan, like worldwide, its role as a source of mobidity and its significant impact on the quality-of-life, onychomycosis becomes a growing public health concern and warrants treatment to achieve complete cure. The mainstay of current treatment modalities for onychomycosis is an oral option using those antifungal agents which have potent in vitro and in vivo activities against dermatophytes and other fungi causing onychomycosis. In Japan and many other countries, only two systemic antifungals, itraconazole (ITCZ) and terbinafine (TBF), have been approved for the oral treatment of onychomycosis. Both drugs have disadvantages that can limit their use in clinical practice due to their limited bioavailability, frequent adverse events, and significant drugdrug interactions. Fosravuconazole L-lysine ethanolate (F-RVCZ), a water-soluble prodrug of ravuconazole, which is a new extended-spectrum triazole with potent activity against dermatophytes, as well as against many non-dermatophyte molds and yeasts. Advantages of the oral formulation of F-RVCZ include excellent bioavailability, pharmacokinetics and other pharmacological properties, and favorable safety profile due to fewer serious adverse effects and fewer drug-drug interactions than those noted with ITCZ and TBF. A Phase III randomized, double-blind, placebo-controlled trial that evaluated efficacy of F-RVCZ dosing 100 mg (as RVCZ) once daily for 12 weeks in patients with toenail omychonycosis due to dermatophytes noted 82.0% mycological cure and 59.4% complete cure. Thus, F-RVCZ is likely to be a valuable addition to the current armamentarium for the oral treatment of onychomycosis and to expand treatment option for the nail infection. As clinical experience increases, the role of this new triazole in the treatment of onychomycosis will be better defined. In this review, the history of synthesis and development, in vitro activity, pharmacological attributes, clinical efficacy and safety profile of F-RVCZ that led to the recent Japanese governmental authorities approval of this drug for the treatment of dermatophytes-causing onychomycosis are comprehensively described.

Tazobactam/piperacillin (Zosyn^®) was approved for peritonitis, intra-abdominal abscess, cholecystitis, and cholangitis as additional indications in September 2012, and a special drug useresults survey was conducted from December 2012 to March 2016 to investigate the safety and efficacy of Zosyn^® in pediatric patients with intraperitoneal infection. A total of 148 patients were enrolled at 32 institutions nationwide, and 148 patients were evaluated for safety and 142 patients for efficacy.

Adverse drug reactions occurred in 12 of the 148 subjects(14 cases), and the incidence was 8.1%. The adverse drug reactions included 6 cases of diarrhea, 2 cases of hepatic function abnormal, 2 cases of rash, and 1 case of each of eyelid edema, liver disorder, pyrexia, and white blood cell count decreased. Of these, 1 case of liver disorder was serious. All of these events are known adverse reactions, and no new adverse reactions were observed. All of the adverse reactions resolved or were resolving.

There was no increase in the incidence of adverse reactions or newly-developed adverse reactions compared to the results of a special drug use-results survey conducted in pediatric patients with sepsis, pneumonia, pyelonephritis, or complicated cystitis, which are the initial indications approved for this drug. However, in this survey, diarrhea, hepatic function abnormal, liver disorder, and rash were also observed as major adverse reactions and were reconfirmed as adverse reactions associated with the use of this drug in pediatric patients that require special attention.

The efficacy rate in the 142 efficacy-evaluable patients was 90.1%. The efficacy rate by disease was 94.0% for peritonitis, 85.7% for intra-abdominal abscess, and 82.4% for cholangitis.

The safety and efficacy results in this survey showed a similar trend to those in the special drug use-results survey conducted in pediatric patients with sepsis, pneumonia, pyelonephritis, or complicated cystitis at the time of the initial approval of this drug. Based on the results obtained in this survey, there were no clinically significant problems in the safety and the efficacy of this drug in pediatric patients with intraperitoneal infection, and this drug was considered useful as a drug for empiric therapy as recommended in clinical practice guidelines for various infectious diseases.

We determined MICs of antibacterial agents against 1,220 clinical strains of aerobic Gramnegative bacteria (18 genus or species) isolated at 15 facilities across Japan in 2014.

The prevalence of extended-spectrum β-lactamases (ESBL) -producing Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, and Proteus mirabilis were 22.4%, 6.3%, 5.8%, and 12.2%, respectively. The ratio of ESBL-producing E. coli has been increasing in this decade, even though the ratio in 2014 was equivalent to that in 2012. Although the prevalence of ESBLproducing K. pneumoniae was lower than that of E. coli, it continued to increase from that in 2006 (2.4%). Almost all of the ESBL-producing E. coli (33 of 34 strains; 97.1%) were harboring CTX-M type enzyme, and most of that (26 of 33 strains) were CTX-M-9 group. The one of the 34 strains had SHV-12 type ESBL enzyme, which was detected for the first time in our surveillance since 1992. Among the ESBL-producing E. coli in 2014, the ratio of levofloxacinresistant strains was 82.4%.

Against glucose-non-fermentative Gram-negative bacteria, the activities of most antibacterial agents were similar to those against the isolates in 2012. The ratio of multidrugresistant Pseudomonas aeruginosa was 1.0%, and the multidrug resistant Acinetobacter was not detected.

We conducted a clinical study of patients who were confirmed to colonize by on-admission screening of vancomycin resistant enterococci (VRE) for 8 years from 2008 to 2016 at Saitama Medical University Hospital. The subjects were 25,779 patients, 53 patients with VRE colonization and a positive rate of 0.20%. The patients colonized VRE were 33 males and 20 females, aged 0 to 95 years (median 68 years). The detected VRE is 47 strains (88.7%) of Enterococcus faecium and 6 strains(11.3%)of Enterococcus faecaclis. Thirty eight strains (80%) of vanA gene and 9 strains(20%)of vanB gene were carried in E. faecium and all 6 strains of E. faecalis possessed the vanA gene. The underlying disease was 14 patients(26%)with malignancy followed by 13 patients(24%)with renal failure and 4 patients (7.5%) with pneumonia.

A target for the carbapenem-resistance rate of Pseudomonas aeruginosa was included in Japan’s “National Action Plan on Antimicrobial Resistance 2016–2020” In order to achieve this target, we need to make efforts to reduce the frequency of carbapenem-resistant P. aeruginosa and to ensure the appropriate use of antimicrobial agents that have the potential to induce bacterial resistance. The effectiveness of the combined use of injectable anti-P. aeruginosa agents other than carbapenems against carbapenem-resistant P. aeruginosa was evaluated using antimicrobial susceptibility data for 286 P. aeruginosa strains that were isolated in 2012.

Based on the interpretation criteria outlined in the Clinical and Laboratory Standards Institute M100-S28 standards, 84 out of 286 P. aeruginosa strains showed resistance or intermediate susceptibility to imipenem or meropenem and were classified as carbapenemresistant. The susceptibility rates of these strains for piperacillin (PIPC), tazobactam/piperacillin (TAZ/PIPC), ceftazidime (CAZ) and cefepime (CFPM) ranged from 58.3–70.2%, and those for ciprofloxacin (CPFX) and levofloxacin (LVFX) were 67.9% and 64.3%, respectively. High susceptibility rates of 88.1% and 92.9% were obtained for gentamicin (GM) and amikacin (AMK), respectively.

PIPC, TAZ/PIPC, CAZ or CFPM, which are β-lactams, were used in combination with CPFX, LVFX, GM, or AMK, and percentage of strains that were susceptible to one or both antimicrobial agents was calculated for each combination. As a result, it was found that combining β-lactams with CPFX or LVFX resulted in susceptibility rates of 64.3–86.9%, and combining β-lactams with GM or AMK produced susceptibility rates of 88.1–96.4%.

In this study, we demonstrated that the susceptibility rates of carbapenem-resistant P. aeruginosa were increased by combining β-lactams with new quinolones or aminoglycosides; i.e., non-carbapenem drugs. It is expected that the promotion of combination therapy involving these antimicrobial agents would lead to a reduction in the frequency of carbapenem resistance among P. aeruginosa.