Effectiveness of cefmetazole versus meropenem for invasive urinary tract infections caused by extended-spectrum ß-lactamase-producing Escherichia coli.

Cefmetazole is active against extended-spectrum ß-lactamase-producing Escherichia coli (ESBLEC) and is a potential candidate for carbapenem-sparing therapy. This multicenter, observational study included patients hospitalized for invasive urinary tract infection due to ESBLEC between March 2020 and November 2021 at 10 facilities in Japan, for whom either cefmetazole or meropenem was initiated as a definitive therapy within 96 h of culture collection and continued for at least 3 d. Outcomes included clinical and microbiological effectiveness, recurrence within 28 d, and all-cause mortality (14 d, 30 d, in-hospital). Outcomes were adjusted for the inverse probability of propensity scores for receiving cefmetazole or meropenem. Eighty-one and forty-six patients were included in the cefmetazole and meropenem groups, respectively. Bacteremia accounted for 43% of the cefmetazole group, and 59% of the meropenem group. The crude clinical effectiveness, 14 d, 30 d, and in-hospital mortality for patients in the cefmetazole and meropenem groups were 96.1% vs 90.9%, 0% vs 2.3%, 0% vs 12.5%, and 2.6% vs 13.3%, respectively. After propensity score adjustment, clinical effectiveness, the risk of in-hospital mortality, and the risk of recurrence were similar between the two groups (P = 0.54, P = 0.10, and P = 0.79, respectively). In all cases with available data (cefmetazole : n = 61, meropenem : n = 22), both drugs were microbiologically effective. In all isolates, bla CTX-M was detected as the extended-spectrum ß-lactamase gene. The predominant CTX-M subtype was CTX-M-27 (47.6%). Cefmetazole showed clinical and bacteriological effectiveness comparable to meropenem against invasive urinary tract infection due to ESBLECs.

Survival case of rhinocerebral and pulmonary mucormycosis due to Cunninghamella bertholletiae during chemotherapy for acute myeloid leukemia: a case report.

A 42-year-old man diagnosed with acute myeloid leukemia complained of progressive swelling of the right side of his face with pain 11 days after the third cycle of consolidation therapy with high-dose arabinosylcytosine-cytarabine. Head and neck magnetic resonance imaging showed a mass lesion in his right maxillary sinus with parapharyngeal involvement, which included the right masseter muscle, intraorbital involvement, and an abscess in his brain. Chest computed tomography revealed peribronchial small nodules in his right upper lobe and a necrotic tumor in his right lower lobe. Molds identified as Cunninghamella bertholletiae were isolated from the necrotic ulcer. According to these results, chemotherapy for leukemia was discontinued. High-dose liposomal amphotericin (10 mg/kg/day) was initiated. Because renal dysfunction occurred, the dosage was decreased to 6 mg/kg and combined with 150 mg/day micafungin. Debridement of necrotic tissue in the right maxillary sinus and establishment of the fenestration between the sinus and oral cavity were performed. Subsequently, brain and lung lesions were surgically removed. Rhinocerebral mucormycosis was successfully treated without relapse over 3 years by a 112-day course of intravenous anti-fungal therapy and 223-day course of terbinafine and partial surgical removal, respectively, to maintain masticatory and ocular functions. To our knowledge, there has been no other report of a long-term survival case of rhinocerebral mucormycosis due to C. bertholletiae.

Rabies post-exposure prophylactic vaccination for returning travelers to Japan.

BACKGROUND: Rabies post-exposure prophylaxis (PEP) in Japan is administered using 6 subcutaneous doses (on days 0, 3, 7, 14, 30, and 90), which is not in line with international recommendations of 4 or 5 intramuscular doses. For reducing dose frequency, we evaluate the immunogenicity of PEP with a regimen of 6 subcutaneous doses. METHOD: This prospective single-center cross-sectional study was performed between September 2013 and December 2014. We included patients underwent rabies PEP by purified chick embryo-cultured rabies vaccine Kaketsuken (PCEC-K) at our clinic, and excluded patients with a history of pre-exposure prophylaxis or PEP using rabies immunoglobulin. The rabies virus-neutralizing antibody tests were performed at the first visit to our office (doses 1-4) and at the fifth and sixth doses. RESULTS: Data were available for 43 of 59 enrolled patients. Thirty-two patients did not start PEP within 48 h after exposure to animals. The seroprotection rates (≥0.5 IU/mL) were 90.7% and 75.7%, at days 30 and 90, respectively. Despite receiving a fifth dose, 85.3% of the patients exhibited decreasing antibody titers during days 30-90 (p < 0.001). CONCLUSIONS: The seroprotection rates of PCEC-K induced subcutaneously were insufficient to prevent rabies at day 30 and 90.

Epidemiology of extended-spectrum beta-lactamase (ESBL) producing Escherichia coli in Japan: Characteristics of community-associated versus healthcare-associated ESBL E. coli.

Data on community-associated extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (CA-ESBLEC) infections in Japan are scarce. We compared the clinical and microbiological epidemiology of CA-ESBLEC infections with that of healthcare-associated-ESBLEC infections among 76 patients with ESBLEC infections. We identified a high prevalence (26%) of CA-ESBLEC infections in Japan; only a small proportion (15%) of patients with CA-ESBLEC infections had recent exposure to antibiotics.

Autochthonous dengue fever, Tokyo, Japan, 2014.

After 70 years with no confirmed autochthonous cases of dengue fever in Japan, 19 cases were reported during August-September 2014. Dengue virus serotype 1 was detected in 18 patients. Phylogenetic analysis of the envelope protein genome sequence from 3 patients revealed 100% identity with the strain from the first patient (2014) in Japan.

Comparison of clinical characteristics and laboratory findings of malaria, dengue, and enteric fever in returning travelers: 8-year experience at a referral center in Tokyo, Japan.

BACKGROUND: Without specific symptoms, diagnosis of febrile illness in returning travelers is challenging. Dengue, malaria, and enteric fever are common causes of fever in returning travelers and timely and appropriate treatment is important. However, differentiation is difficult without specific diagnostic tests. METHODS: A retrospective study was conducted at the National Centre for Global Health and Medicine (NCGM) from April 2005 to March 2013. Febrile travelers returning from overseas who were diagnosed with dengue, malaria, or enteric fever were included in this study. Clinical characteristics and laboratory findings were compared for each diagnosis. RESULTS: During the study period, 86 malaria, 85 dengue, and 31 enteric fever cases were identified. The mean age of the study cohort was 33.1 ± 12 years and 134 (66.3%) study participants were male. Asia was the most common area visited by returning travelers with fevers (89% of dengue, 18.6% of malaria, and 100% of enteric fever cases), followed by Africa (1.2% of dengue and 70.9% of malaria cases). Clinical characteristics and laboratory findings were significantly different among each group with each diagnosis. Decision tree models revealed that returning from Africa and CRP levels <10 mg/L were factors specific for diagnosis of malaria and dengue fever, respectively. CONCLUSION: Clinical manifestations, simple laboratory test results, and regions of travel are helpful to distinguish between dengue, malaria, and enteric fever in febrile returning travelers with non-specific symptoms.

Gene polymorphisms of mannose-binding lectin confer susceptibility to Pneumocystis pneumonia in HIV-infected patients.

BACKGROUND: Mannose-binding lectin (MBL) plays an important role in innate immunity. The aim of this study was to determine whether genetic variants of MBL confer susceptibility to Pneumocystis pneumonia (PCP) in patients with advanced human immunodeficiency virus (HIV) infections. OBJECTIVE: HIV patients (n = 53) having CD4 counts <200/µL who were admitted to our hospital were analyzed. Of these 53 patients, 30 had PCP at admission, and 23 did not. Genotypes at six single nucleotide polymorphisms (SNP) in MBL2 gene and serum MBL levels were determined for each patient, and compared between patients with or without PCP. We also examined whether MBL enhances phagocytosis of macrophages against rat-type Pneumocystis organism in vitro. RESULTS: Genotypes associated with low production of MBL were significantly more common in the PCP group than in the non-PCP group (P = 0.049, odds ratio 2.17, 95% CI 1.02-4.63). Serum MBL levels were significantly higher in the non-PCP group (P = 0.039). Findings from in vitro experiments indicated that MBL act as a direct opsonin enhancing macrophage-mediated phagocytosis of Pneumocystis organisms. CONCLUSION: Genetic variation of MBL production influences susceptibility to PCP in patients with advanced HIV infection, and can be regarded as a risk factor for PCP.

Travel-related leptospirosis in Japan: a report on a series of five imported cases diagnosed at the National Center for Global Health and Medicine.

Leptospirosis is one of the most common travel-related infections. We report 5 cases of travel-related leptospirosis who presented at our clinic between January 2008 and December 2013. Patients were included in the study if they presented with a clinical profile that was compatible with the disease within 21 days of their return from traveling, which were laboratory-diagnosed as leptospirosis by blood culture, rise in antibody titers in paired sera using the microscopic agglutination test (MAT), and/or DNA detection using flaB-nested PCR. Five leptospirosis cases were evaluated, all of which contracted the disease after exposure to fresh water in Southeast Asian countries. All of the cases had fevers, headaches, conjunctival injections, and relative bradycardia. The pertinent laboratory findings included elevated C-reactive protein levels, elevated creatinine levels, and sterile pyuria. All 5 cases had serum MAT titers that increased by ≥ 4 times in the interval between specimens taken during the acute phase and those taken during the convalescence phase, and leptospiral DNA was detected in plasma and/or urine specimens in 4 cases. Leptospira interrogans was isolated from one patient's blood sample. Patients were treated with penicillin G, minocycline, or doxycycline. One case was cured without antibiotics. A diagnosis of leptospirosis should be considered for febrile travelers who return from Southeast Asian countries to Japan after being exposed to freshwater while traveling.

Multidrug-resistant Acinetobactor baumannii isolated from a traveler returned from Brunei.

We report a case of multidrug-resistant (MDR) Acinetobactor baumannii isolates obtained from a traveler returned from Brunei. Whole-genome sequencing analysis revealed that the isolates harbored blaOxA-23 and armA. The minimum inhibitory concentrations of antibiotics against the strain were as follows: imipenem, 32 µg/ml; meropenem, 32 µg/ml; ciprofloxacin, 16 µg/ml; amikacin, ≧ 1024 µg/ml; arbekacin, ≧ 1024 µg/ml; aztreonam, 64 µg/ml; colistin, 4 µg/ml. A. baumannii harboring both blaOxA-23 and armA is rarely reported in Japan, and, to the best of our knowledge, this is the second report of A. baumannii harboring both resistant genes in Japan.

Comparison of clinical characteristics and laboratory findings of malaria, dengue, and enteric fever in returning travelers: 8-year experience at a referral center in Tokyo, Japan.

BACKGROUND: Without specific symptoms, diagnosis of febrile illness in returning travelers is challenging. Dengue, malaria, and enteric fever are common causes of fever in returning travelers and timely and appropriate treatment is important. However, differentiation is difficult without specific diagnostic tests. METHODS: A retrospective study was conducted at the National Centre for Global Health and Medicine (NCGM) from April 2005 to March 2013. Febrile travelers returning from overseas who were diagnosed with dengue, malaria, or enteric fever were included in this study. Clinical characteristics and laboratory findings were compared for each diagnosis. RESULTS: During the study period, 86 malaria, 85 dengue, and 31 enteric fever cases were identified. The mean age of the study cohort was 33.1 ± 12 years and 134 (66.3%) study participants were male. Asia was the most common area visited by returning travelers with fevers (89% of dengue, 18.6% of malaria, and 100% of enteric fever cases), followed by Africa (1.2% of dengue and 70.9% of malaria cases). Clinical characteristics and laboratory findings were significantly different among each group with each diagnosis. Decision tree models revealed that returning from Africa and CRP levels < 10 mg/L were factors specific for diagnosis of malaria and dengue fever, respectively. CONCLUSION: Clinical manifestations, simple laboratory test results, and regions of travel are helpful to distinguish between dengue, malaria, and enteric fever in febrile returning travelers with non-specific symptoms.

Case report: failure under azithromycin treatment in a case of bacteremia due to Salmonella enterica Paratyphi A.

BACKGROUND: Limited information is available regarding the clinical efficacy of azithromycin for the treatment of enteric fever due to fluoroquinolone-resistant Salmonella Typhi and Salmonella Paratyphi among travelers returning to their home countries. CASE PRESENTATION: We report a case of a 52-year-old Japanese man who returned from India, who developed a fever of 39°C with no accompanying symptoms 10 days after returning to Japan from a 1-month business trip to Delhi, India. His blood culture results were positive for Salmonella Paratyphi A. He was treated with 14 days of ceftriaxone, after which he remained afebrile for 18 days before his body temperature again rose to 39°C with no apparent symptoms. He was then empirically given 500 mg of azithromycin, but experienced clinical and microbiological failure of azithromycin treatment for enteric fever due to Salmonella Paratyphi A. However, the minimum inhibitory concentration (MIC) of azithromycin was not elevated (8 mg/L). He was again given ceftriaxone for 14 days with no signs of recurrence during the follow-up. CONCLUSION: There are limited data available for the treatment of enteric fever using azithromycin in travelers from developed countries who are not immune to the disease, and thus, careful follow-up is necessary. In our case, the low azithromycin dose might have contributed the treatment failure. Additional clinical data are needed to determine the rate of success, MIC, and contributing factors for success and/or failure of azithromycin treatment for both Salmonella Typhi and Salmonella Paratyphi infections.

[Malaria cases treated with artemether/lumefantrine in Japanese travelers].

Artemisinin-based combination therapy (ACT) has been the standard treatment for uncomplicated malaria. Although not licensed in Japan, artemether/lumefantrine (AL), one type of ACT, has been administered to patients with malaria since 2002 by the Research Group on Chemotherapy of Tropical Diseases. Herein, we reviewed malaria cases treated with AL in Japanese travelers. A retrospective study was conducted at the National Center for Global Health and Medicine from October 2005 to March 2013. There were 19 malaria patients treated with AL, and 10 falciparum malaria patients treated with AL only. In these 10 patients treated with AL only, the median time of fever clearance was 25.0 hours (range:14-66 hours), and the median time of parasite clearance was 36.0 hours (range:16-62 hours). There was a positive correlation between parasitemia and time from the start of therapy to the disappearance of the parasites. Parasitemia was higher (4.05% vs. 0.24%; p = 0.044) and parasite clearance time was longer (55.5 hours vs. 31.5 hours; p = 0.044) in the cases of recrudescence than non-recrudescence, respectively. Three of the 19 malaria patients showed recrudescence of malaria after treatment with AL. The reason that treatment failure was more frequently observed in this study than in previous reports may be related to poor absorption of lumefantrine owing to gastrointestinal symptoms, insufficiently ingested fatty foods, or high parasitemia on admission. The World Health Organization recommends that intravenous antimalarials should be administered in cases of severe malaria however, this is not applicable in Japan. Further studies are needed to distinguish patients with malaria who are treatable with ACT from those who should be treated initially with other intravenous antimalarials.

Clinical Characteristics of Retroviral Rebound Syndrome: A Case Report and Literature Review.

We herein report a case of retroviral rebound syndrome (RRS) complicated with hemophagocytic lymphohistiocytosis. Owing to the paucity of comprehensive data on RRS, we also conducted a literature review. All 19 cases included in the review presented within 2 months after the discontinuation of antiretroviral therapy. They were usually accompanied by both a significant decrease in CD4 count (median 292/µL) and a rapid increase in plasma human immunodeficiency virus loads (median 3.5×105/mL). Although life-threatening complications were reported, the overall prognosis was favorable. The outcomes of this review aided in the diagnosis of the present case.

Aseptic Cavernosal Abscess: An Unrecognized Feature of Neutrophilic Dermatosis.

A 50-year-old man developed a sterile cavernosal abscess followed by prominent features of necrotizing neutrophilic dermatosis. We conducted a literature review, which revealed that aseptic abscesses in the corpus cavernosum occur in association with neutrophilic dermatosis. Patients with this condition frequently receive unnecessary antibiotic treatment and surgical interventions. Although this condition responds to systemic corticosteroids, the functional prognosis of the penis is poor. Abscess formation may be the initial presentation of neutrophilic dermatoses, and underlying conditions may even be absent. Clinicians need to be aware of this condition to distinguish it from bacterial infection and initiate early disease-specific treatments.

Prognostic factors and outcomes of adult patients with acute myeloid leukemia after first relapse.

BACKGROUND: Patients with acute myeloid leukemia who are treated with conventional chemotherapy still have a substantial risk of relapse; the prognostic factors and optimal treatments after relapse have not been fully established. We, therefore, retrospectively analyzed data from patients with acute myeloid leukemia who had achieved first complete remission to assess their prognosis after first relapse. DESIGN AND METHODS: Clinical data were collected from 70 institutions across the country on adult patients who were diagnosed with acute myeloid leukemia and who had achieved a first complete remission after one or two courses of induction chemotherapy. RESULTS: Among the 1,535 patients who were treated with chemotherapy alone, 1,015 relapsed. Half of them subsequently achieved a second complete remission. The overall survival was 30% at 3 years after relapse. Multivariate analysis showed that achievement of second complete remission, salvage allogeneic hematopoietic cell transplantation, and a relapse-free interval of 1 year or longer were independent prognostic factors. The outcome after allogeneic transplantation in second complete remission was comparable to that after transplantation in first complete remission. Patients with acute myeloid leukemia and cytogenetic risk factors other than inv(16) or t(8;21) had a significantly worse outcome when they did not undergo salvage transplantation even when they achieved second complete remission. CONCLUSIONS: We found that both the achievement of second complete remission and the application of salvage transplantation were crucial for improving the prognosis of patients with acute myeloid leukemia in first relapse. Our results indicate that the optimal treatment strategy after first relapse may differ according to the cytogenetic risk.

Serum KL-6 level is a useful biomarker for evaluating the severity of coronavirus disease 2019.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is currently spreading worldwide. This study examined whether serum Krebs von den Lungen-6 (KL-6) level is a useful biomarker for evaluating the severity of COVID-19. METHODS: We retrospectively examined patients diagnosed with COVID-19 at the Japanese Red Cross Medical Center between February 1, 2020, and May 15, 2020. Patients were divided into four categories based on clinical and radiological findings: mild, moderate, severe, and critical. Patients who presented with a mild or moderate illness and patients who started with or worsened to a severe or critical illness were classified as the non-severe and severe groups, respectively. The two groups were compared for patient characteristics, including serum KL-6 levels. Receiver operating characteristic curves were used to define the optimum cut-off value of serum KL-6 level to evaluate COVID-19 severity. RESULTS: A total of 54 patients were enrolled, including 33 in the non-severe group and 21 in the severe group, of which four died. Compared with those in the non-severe group, more patients in the severe group were significantly older and had comorbidities. Serum KL-6 levels were significantly higher in the severe group than in the non-severe group both at diagnosis (median, 338 U/mL) and at peak levels within one week after diagnosis (median, 781 U/mL) (both p < 0.001). Serum KL-6 value at peak level (371 U/mL) was used as the optimal cut-off to evaluate disease severity (sensitivity, 85.7%; specificity, 96.6%). CONCLUSIONS: Serum KL-6 levels were significantly elevated in severe COVID-19 and is useful for evaluating its severity.

Anxiety, Depression, and Resilience of Healthcare Workers in Japan During the Coronavirus Disease 2019 Outbreak.

Objective Coronavirus disease 2019 (COVID-19) is spreading around the world. The aim of this study was to assess the degree of anxiety, depression, resilience, and other psychiatric symptoms among healthcare workers in Japan during the COVID-19 pandemic. Methods This survey involved medical healthcare workers at the Japanese Red Cross Medical Center (Tokyo, Japan) between April 22 and May 15, 2020. The degree of symptoms of anxiety, depression, and resilience was assessed using the Japanese versions of the 7-item Generalized Anxiety Disorder Scale (GAD-7), Center for Epidemiologic Studies Depression Scale (CES-D), and 10-item Connor-Davidson Resilience Scale. Furthermore, we added original questionnaires comprising three factors: (i) anxiety and fear of infection and death; (ii) isolation and unreasonable treatment; and (iii) motivation and escape behavior at work. Results In total, 848 healthcare workers participated in this survey: 104 doctors, 461 nurses, 184 other co-medical staff, and 99 office workers. Among all participants, 85 (10.0%) developed moderate-to-severe anxiety disorder, and 237 (27.9%) developed depression. Problems with anxiety and fear of infection and death, isolation and unreasonable treatment, and motivation and escape from work were higher in the depression group than in the non-depression group (total CES-D score ≥ 16 points). Being a nurse and high total GAD-7 scores were risk factors of depression. Older workers and those with higher resilience were less likely to develop depression than others. Conclusion During the COVID-19 epidemic, many healthcare workers suffered from psychiatric symptoms. Psychological support and interventions for protecting the mental health of them are needed.

The 2014 autochthonous dengue fever outbreak in Tokyo: A case series study and assessment of the causes and preventive measures.

OBJECTIVE: In 2014, an autochthonous dengue fever outbreak occurred around the Yoyogi Park in Japan for the first time in 70 years. Despite no local cases reported since then, the risk of another outbreak remains high. This study reviews the autochthonous dengue fever cases of the outbreak, investigates its causes, and delineates preventive measures against autochthonous dengue epidemics. METHODS: We conducted a case series study of 15 patients who visited our institution during the 2014 outbreak. We collected and evaluated data on the surveillance of vector mosquitoes, weather, pest control, travelers' origins and destinations, and imported dengue fever cases using reports made by public institutions. RESULTS: All patients recovered with supportive treatments and none met the diagnostic criteria for severe dengue infection. Twelve patients with positive real-time polymerase chain reactions were confirmed as having dengue virus-1 infections. We found no obvious associations between the number of mosquitoes and the weather, or between the number of imported dengue fever cases and that of travelers. Insect growth regulator (IGR) against vector mosquitoes has been used since 2014 for pest control, but the number of larvae has not declined in the Yoyogi Park, although that of imagoes has been relatively suppressed. CONCLUSION: The 2014 outbreak emerged without particularly favorable climate conditions for vector mosquitoes. We found no obvious associations between the number of travelers or the imported dengue fever cases and the outbreak, but the increasing number of travelers may contribute to another outbreak. Pest control, including IGR, remains essential for infection control.

[IgM-lambda multiple myeloma presenting with systemic amyloidosis].

A 59-year-old man was referred to our hospital due to nephrotic syndrome with IgM paraproteinemia. Physical examination demonstrated marked hepatomegaly and anasarca. Serum M-protein was 0.94 g/dl and urinary analysis detected the presence of Bence Jones protein. Bone marrow plasma cell count was 11.2%. Histological examination demonstrated AL-type amyloid deposition in the liver, kidneys, bone marrow, stomach and rectum. These findings led to a diagnosis of IgM multiple myeloma with systemic amyloidosis. Although there was no apparent response to 2 courses of vincristine, doxorubicin and dexamethasone (VAD) regimen, subsequent treatment with bortezomib in combination with dexamethasone resulted in a rapid reduction in M protein to 0.49 g/dl, approximately half the pre-treatment level.