Metronidazole is an antibiotic classically used against most anaerobic bacteria and protozoa. Because an intravenous form of metronidazole has recently entered the market, the use of this antibiotic is attracting renewed interest in many clinical settings in Japan. However, neurotoxicityisa major adverse event: in the central nervous system metronidazole-induced encephalopathy is a rare but serious condition. We performed a literature review of 34 cases including 2 of our cases, 25 from domestic conference abstracts, and 7 cases presented in full research papers. The mean patient age was 64.7 years. The conditions most commonly treated with metronidazole were brain abscess (35.3％), liver abscess (17.6％), and Clostridium difficile infection (14.7％). The most common predisposing conditions were liver dysfunction (26.5％), diabetes and other metabolic disorders (20.6％), and hematologic or solid organ malignancy (14.7％). The mean period of administration before the onset of encephalopathy symptoms was 61.3 days, and the mean total dose was 95.9g. The initial chief complaints were dysarthria (in 70.6％of the cases) and ataxia (61.8％) ; 82.4％of the cases were diagnosed on the basis of MRI (T2-weighted or FLAIR imaging). The key imaging finding was high intensity in the dentate nucleus bilaterally (82.4％). Stopping the metronidazole led to symptom remission within 8.5 days, but the MRI changes remained longer than the clinical symptoms. Two patients (6.0％) developed irreversible disturbance of consciousness. Although the mechanisms of this type of encephalopathy have not yet been elucidated, localized nerve-cell edema is likely caused by decreased metronidazole metabolism associated with liver and metabolic dysfunction. Careful observation for neurologic signs should be conducted during the treatment of brain abscesses associated with metronidazole administration, because patients with brain abscesses are naturally at high risk of metronidazole-induced encephalopathy.

View full abstract

In 2014, we reported the first trial based on outpatient parenteral antimicrobial therapy (OPAT) with continuous infusions in Japan. Following this, we found many patients who were eligible for OPAT but could not undertake it owing to difficulties in accessing the clinic daily. To overcome this problem, we created a model in collaboration with visiting nursing stations and started providing OPAT with the services. We report herein on a summary of the investigation of the first 10 patients treated under this model. We collected data pertaining to diseases, organisms, antimicrobials, treatment duration, bed days saved, outcome, readmission rate, and cost reductions associated with these patients. The most commonly targeted disease was osteomyelitis, followed by infective endocarditis. The condition of nine of the patients was complicated by bacteremia. The most commonly targeted organism was Staphylococcus aureus. Cefazolin was the most frequently prescribed antimicrobial, followed by Penicillin G. The median duration for OPAT was 12 days (range : 5～23 days). The total number of bed days saved was 129. All patients completed the planned OPAT. Eight patients were cured and two showed improvement. Only one patient was readmitted within a month after the completion of therapy. The estimated medical cost reduction was 496,540 yen, which is approximately 4,200 US dollars. Collaboration with visiting nursing stations provided OPAT to the patients who had difficulties in accessing the clinic daily. Our study shows that OPAT administered by continuous infusion in collaboration with home-visit nursing services would be a safe and feasible practice for efficient bed utilization and medical cost saving.

View full abstract

We evaluated the usefulness of IMMUNOCATCH-RSV (Eiken chemical Co., Ltd.) (IC-A), a newly developed immunochromatographic assay kit for detection of respiratory syncytial virus (RSV). For the clinical study, 210 nasal swabs and 134 nasopharyngeal aspirates were collected from pediatric patients with acute respiratory tract infections in 2013. Three immunochromatographic assay kits (IC-A, ICB and IC-C), and the RT-PCR method were used for the detection of RSV. The detection times for IC-A, ICB and IC-C were 8, 15 and 10 minutes, respectively. The positive rates for IC-A using nasal swabs and nasopharyngeal aspirates were 33.8％and 35.8％, respectively. For the nasal swab specimens, the total concordance rates of RT-PCR with IC-A, IC-B and IC-C were 96.2％(202/210), 89.5％(188/210), and 90.5％(143/158), respectively. As for the nasopharyngeal aspirates, the total concordance rates of RT-PCR with IC-A, IC-B and IC-C were 96.3％(129/134), 94.0％(125/133), and 97.7％(130/133), respectively. The minimum detection concentration of IC-A was 3.0×10²TCID₅₀/mL for the RSV subgroup A strain,and 7.5×10 TCID₅₀/mL for the RSV subgroup B strain. In conclusion, the current data indicate that IC-A is a useful kit for more rapid and accurate detection of RSV infection.

View full abstract

Escherichia coli is the most commonly isolated bacterium in urinary tract infections, especially in acute uncomplicated cystitis. It is reported that fluoroquinolone-resistant E. coli is increasing. However, according to the guidelines for antimicrobial use published by the Japanese Associations for Infectious Diseases (JAID) and the Japanese Society of Chemotherapy (JSC) in 2014, the first line antimicrobial regimen for the treatment of acute uncomplicated cystitis is a 3-day regimen with fluoroquinolone. We analyzed the causative bacteria and clinical efficacy of antimicrobial treatment in acute uncomplicated cystitis cases at our institute. Patients diagnosed as having acute uncomplicated cystitis who had ≧104 colony-forming units/mL of bacteria in their midstream urine in our outpatient clinic between 2012 and 2013 were enrolled in this study. We analyzed their clinical data retrospectively. From 173 patients, 212 strains were isolated. Of these, 135 (63.7％) were E. coli, including 15 strains (11.1％) that were levofloxacin resistant. One hundred twenty-three patients (63.7％) were treated with cephalosporin, and 46 patients (26.6％) were treated with fluoroquinolone. In all, 140 patients (80.9％) visited the outpatient clinic for an average of 8.4 days after their treatment. For 130 patients (92.6％), the clinical outcomes of antimicrobial treatment were judged as effective. The clinical outcomes were effective in 92.1％of the patients with cephalosporin treatment and in 97.1％of those with fluoroquinolone treatment. Only one patient who had levofloxacin-resistant E. coli in her urine was treated with fluoroquinolone. The clinical outcome was effective. Of the E. coli isolated from acute uncomplicated cystitis patients, 11.1％were levofloxacin-resistant strains. However, the clinical efficacy of antimicrobial treatment was relatively high (92.9％) in this study. The antimicrobial treatment for acute uncomplicated cystitis recommended by the guidelines published by the JAID and JSC was effective in the current situation.

View full abstract

Although most of commonly used antimicrobial agents had been susceptible to Esherichia coli, recently there are a lot of reports concerning about community-acquired infection caused by resistant E. coli.The aim of this study is to define the prevalence of resistant E. coli in normal flora colonization by the rectal swab method. From June 2009 to December 2013, 251 male patients (50～85 year-old, median 68) planned to transrectal prostate biopsy participated in this study. Stools stuck on the glove at the digital examination were provided for culture specimen. Identification of E. coli and determination of MIC was performed by MicroScan WalkAway40plus (Siemens). Isolated E. coli were deemed quinolone-resistant strains when their MIC of levofloxacine was 4μg/mL or above according to the breakpoint MIC by the CLSI criteria. ESBL producing ability was determined by the double disk method used by CVA contained ESBL definition disc (Eikenkagaku). Of the 251 study patients, 224 patients had positive cultures of E. coli. Twenty-four patients had quinolone-resistant strains and 9 patients had ESBL producing strains. The prevalence of quinolone-resistant strains in 2009, 2010, 2011, 2012 and 2013 were 5.9％(2 out of 34 strains), 13.5％(5 out of 37 strains), 12.5％(4 out of 32 strains), 9.0％(6 out of 67) and 13.0％(7 out of 54 strains), respectively. The prevalence of ESBL producing strains in 2009, 2010, 2011, 2012 and 2013 were 0％(0 out of 34 strains), 5.4％(2 out of 37 strains), 3.1％(1 out of 32 strains), 3.0％(2 out of 67 strains) and 7.4％(4 out of 54 strains), respectively. In 2013, the prevalence of antimicrobial resistant E. coli, both quinolone-resistant and ESBL producing strains, were increasing. We have to pay a close attention to the increase ofresistantE. coli. Although most of commonly used antimicrobial agents had been susceptible to Esherichia coli, recently there are a lot of reports concerning about community-acquired infection caused by resistant E. coli.The aim of this study is to define the prevalence of resistant E. coli in normal flora colonization by the rectal swab method. From June 2009 to December 2013, 251 male patients (50～85 year-old, median 68) planned to transrectal prostate biopsy participated in this study. Stools stuck on the glove at the digital examination were provided for culture specimen. Identification of E. coli and determination of MIC was performed by MicroScan WalkAway40plus (Siemens). Isolated E. coli were deemed quinolone-resistant strains when their MIC of levofloxacine was 4μg/mL or above according to the breakpoint MIC by the CLSI criteria. ESBL producing ability was determined by the double disk method used by CVA contained ESBL definition disc (Eikenkagaku). Of the 251 study patients, 224 patients had positive cultures of E. coli. Twenty-four patients had quinolone-resistant strains and 9 patients had ESBL producing strains. The prevalence of quinolone-resistant strains in 2009, 2010, 2011, 2012 and 2013 were 5.9％(2 out of 34 strains), 13.5％(5 out of 37 strains), 12.5％(4 out of 32 strains), 9.0％(6 out of 67) and 13.0％(7 out of 54 strains), respectively. The prevalence of ESBL producing strains in 2009, 2010, 2011, 2012 and 2013 were 0％(0 out of 34 strains), 5.4％(2 out of 37 strains), 3.1％(1 out of 32 strains), 3.0％(2 out of 67 strains) and 7.4％(4 out of 54 strains), respectively. In 2013, the prevalence of antimicrobial resistant E. coli, both quinolone-resistant and ESBL producing strains, were increasing. We have to pay a close attention to the increase ofresistant E. coli.

View full abstract

In the same manner as syphilis, tuberculosis (TB) was often called “The Great Imitator”. We have to consider not only malignancies but also TB as a differential diagnosis when we find any tumorous regions. We report herein on a rare case, clavicular osteomyelitis due to TB. A 72-year-old female, with diabetic nephropathy, was on maintenance hemodialysis. She had a fall 2 months prior to admission followed by pain around her right clavicle. Ulceration occurred in that region a month prior to admission, and CT scan revealed a fracture of the right clavicle with a tumor surrounding that area. Seven days prior to admission, she went to a neurologist because of dizziness. MRI of the brain revealed a tumor in her pons. The physician suspected the tumor was metastasis. Needle biopsies revealed only necrotic tissue so the medical oncologist consulted us because they suspected it was caused by infection of some kind. From the patientʼs history and the physical examination, we suspected TB osteomyelitis and grew some more cultures, but only MRSA and E. coli were detected. We administered vancomycin and cefmetazole for the secondary bacterial osteomyelitis. After a month of hospitalization, we found miliary regions on her chest CT and Mycobacterium tuberculosis was grown from the needle biopsy specimen. We started multi-antituberculosis therapy and the patient had a good prognosis. We report herein on a rare case of clavicular osteomyelitis due to TB, together with a review of the literature.

View full abstract

Severe fever with thrombocytopenia syndrome (SFTS) is a recently identified emerging viral infectious disease in China that is caused by a novel phlebovirus in the family Bunyaviridae,SFTS virus, with an average case fatality rate of 12～30％. A cytokine storm with abnormally expressed cytokine profiles is associated with the disease severity. Hemophagocytic lymphohistiocytosis (HLH) is an aggressive and life threatening syndrome associated with excessive immune activation. We report herein on a fatal case of SFTS complicated by HLH. Consecutive plasma exchange and immunomodulatory therapy was ineffective in our case. The pathognomonic histological feature was necrotizing lymphadenitis with massive hemophagocytosis of systemic lymphoid tissues with SFTS viruses and SFTS-RNA copies. No specific treatment of SFTS is available, and an effective treatment strategy for patients with rapidly progressing SFTS has not been established. Appropriate immunomodulatory therapy is necessary for SFTS patients complicated by HLH.

View full abstract

We report herein on two cases of Japanese spotted fever (JSF) treated with intravenous minocycline (MINO) and levofloxacin (LVFX). An 80 year-old woman (Case1) and a 63 year-old man (Case2) with high fever (＞39℃) and wide-spread skin erythema were admitted because they were suspected of having developed JSF. After admission, we treated them with intravenous MINO and LVFX. The patientsʼfevers were resolved within 36 hours after antibiotics. They were diagnosed as having JSF based on the serological test,and Rickettsia japonica was detected from the genetic findings (PCR analysis from eschar) only in case 1. In the treatment of fulminant JSF (body temperature＞39℃) the prompt administration of a combination of tetracycline and new quinolone has been recommended. The number of cases of JSF and its endemic area are gradually increasing in Japan. As for new quinolones, ciprofloxacin and tosufloxacin have been used against to JSF in Japan, but LVFX may become a new option.

View full abstract

A Japanese female in her 60ʼs on 5 yearsʼtreatment with prednisolone 5mg for ulcetarive colitis developed severe bloody stools and diarrhea and was admitted. A total colectomy was performed because leukocytapheresis with intravenous corticosteroid administration (prednisolone 70mg/day) relieved her symptoms partially. Pneumocystis pneumonia (PCP) prophylaxis was not introduced then. She developed acute respiratory failure on postoperative day (POD) 8, and was intubated and moved to our intensive care unit. PCP was suspected and sulfamethoxazole/trimethoprim (ST) was started with methylprednisolone 40mg/day. The pneumonia initially improved but got worse around POD 27 and pulse corticosteroid therapy was administered. Antibiotics were first changed to pentamidine and finally changed to clindamycin/primaquine because of adverse reactions due to both of the medications. She recovered fully and experienced no exacerbation after discontinuation of the secondary prophylaxis. This is the first report of primaquine administration for PCP in Japan. Clindamycin/primaquine are second-line drugs but very important because the first-line medications such as ST and pentamidine cause adverse reactions and frequently result in discontinuation, as was the case in our present patient. Nowadays immunosuppresive therapy for malingnancies and autoimmune diseases has been introduced more frequently than before, PCP has attracted more attention. Therefore primaquine should be approved for appropriate use without delay in Japan.

View full abstract