Trends in inpatient antimicrobial consumption using days of therapy and days of antibiotic spectrum coverage: A nationwide claims database study in Japan.

INTRODUCTION: Days of antibiotic spectrum coverage (DASC), a novel metric for both antimicrobial volume and spectrum, was proposed to measure inpatient antimicrobial consumption in 2022. The DASC may better reflect efforts toward antimicrobial stewardship; however, no previous study has described the distribution of trends in DASC in hospitals or the association between the trend in DASC and days of therapy (DOT). This study assessed trends in antimicrobial consumption for inpatients at acute care hospitals in Japan using the DOT and DASC. METHODS: This retrospective observational study used the nationwide administrative inpatient claims database of Japanese acute care hospitals between 2014 and 2018. The prescriptions of all antibiotics were identified to calculate DOT/1000 patient-days, DASC/1000 patient-days, and DASC/DOT. We described the five-year trend in these metrics and examined the association between the trends in DOT and DASC. RESULTS: In total, 26,301,685 admissions from 634 hospitals were included. The DOT/1000 patient-days and DASC/1000 patient-days increased significantly by 6.1% and 5.6%, respectively. The DASC/DOT ratio did not change significantly (P = 0.35). Moreover, there was little correlation between DOT/1000 patient-days and DASC/DOT (R2 = 0.01). There was also little correlation between the five-year changes in DOT/1000 patient-days and those in DASC/DOT (R2 = 0.02). CONCLUSIONS: It may be difficult to assess trends in the antibiotic spectrum using DASC alone. However, the combination of DOT as a quantity indicator and DASC/DOT as a spectrum indicator may allow for a more appropriate evaluation of stewardship efforts.

Seronegative HIV-1 infection in a Japanese man presenting with Pneumocystis pneumonia: Analysis of long-term antibody response and literature review.

Seronegative human immunodeficiency virus (HIV) infection, where an HIV-specific antibody response is lacking even in chronic or late-stage HIV infections, is extremely rare. Here, we report the case of a 50-year-old Japanese man presenting with Pneumocystis pneumonia who did not produce antibodies against HIV-1 until the initiation of antiretroviral therapy (ART). Fourth-generation antigen-antibody testing temporarily reverted from weakly positive to negative soon after initiating ART, likely due to a reduction in viral load (assessed by p24 antigen levels). His HIV-1 antibody titers remained low or indeterminate even after four years of ART. A literature review suggested that the absence of HIV-1-specific antibody production may be associated with unimpeded HIV replication and rapid CD4+ T cell decline. Seronegative HIV infection can lead to deferred diagnosis and treatment, thereby increasing the risk of transmitting the virus to others or developing opportunistic illnesses. It is important to combine multiple tests for diagnosis, depending on the medical condition. Further studies are required to investigate the host factors involved in the production of HIV-1-specific antibodies.

The five-year trends in antibiotic prescription by dentists and antibiotic prophylaxis for tooth extraction: a region-wide claims study in Japan.

BACKGROUND: Antimicrobial stewardship in dentistry and antibiotic prophylaxis for tooth extraction have been areas of concern in Japan, with limited research available. METHODS: This cross-sectional study utilized the regional health insurance claims database in Japan to examine antibiotic prescription trends by dentists, including antibiotic regimens, timing of prescription, and days of supply for prophylactic antibiotic use during tooth extraction. Antibiotic prophylaxis for patients with prosthetic heart valves was also investigated. FINDINGS: Antibiotic prescriptions by dentists decreased by 7% in 2019 compared to those in 2015, with third-generation cephalosporins still accounting for 48.5% in 2019. Amoxicillin prescription increased 3.9 times in 2019, although it only accounted for 8.4% of all antibiotic prescriptions. In 2019, amoxicillin was prescribed for 17.1% of all prophylactic antibiotics associated with tooth extraction, and 80% of prophylactic antibiotics were prescribed for 3 days or more, with 85% prescribed on the day of the procedure. However, only 60-70% of patients with prosthetic heart valves received antibiotic prophylaxis. INTERPRETATION: Despite the increasing trend after the implementation of the National Action Plan on antimicrobial resistance, the proportion of amoxicillin prescriptions in dentistry remains low. Antimicrobial stewardship issues related to long-term prescription and timing of administration of prophylactic antibiotics for tooth extraction should be addressed. Dentists must recognize the risks associated with high-risk patients with prosthetic heart valves who require antibiotic prophylaxis, and physicians providing valve replacement therapy should inform patients of the requirement for prophylaxis before invasive dental procedures.

Serum chemokine CC-motif ligand 17 is a predictive marker of severe COVID-19 in haemodialysis patients: A retrospective observational study.

BACKGROUND: Maintenance haemodialysis (HD) patients are at higher risk for severe coronavirus disease 2019 (COVID-19). Because of a limited number of facilities that can provide inpatient treatment for COVID-19 and HD, it is important to identify HD patients who are at high risk for severe COVID-19. For mild to moderate COVID-19 patients, chemokine CC-motif ligand 17 (CCL17) was reported to be a predictive marker for severe COVID-19; however, the validity of CCL17 among HD patients is unknown. METHODS: This retrospective observational study enrolled 107 HD patients with mild or moderate COVID-19 at hospitalization (mean age 70.1 ± 15.1 years; 71.0% male). Receiver operating characteristic and logistic regression analyses were used to examine the predictive validity of indices for severe COVID-19. RESULTS: During hospitalization, 32 patients developed severe COVID-19. Serum CCL17 collected at admission exhibited a higher area under the curve value (0.818) compared with that of other indicators including lactate dehydrogenase and C-reactive protein for the prediction of severe COVID-19. The optimal cut-off value for CCL17 was 150.5 pg/mL. A multi-variate logistic analysis revealed that CCL17 (above 150.5 pg/mL) was significantly associated with severe COVID-19 (Odds ratio, 0.063; 95% Confidence interval [CI], 0.017-0.227; p < .001) even after adjustment for covariates. The addition of the CCL17 to a model consisting of vaccination status, albumin, blood urea nitrogen, C-reacting protein and lactate dehydrogenase significantly improved classification performance for severe COVID-19 using the net reclassification (1.16, 95% CI: 0.82-1.50, p < .001) and integrated discrimination (0.18, 95% CI: 0.09-0.26, p < .001) improvement. CONCLUSION: CCL17 levels in HD patients with mild or moderate COVID-19 predict risk of developing severe COVID-19.

Emergence of Hepatitis C Virus Genotype 2c Infection Among Human Immunodeficiency Virus-Infected Men Who Have Sex With Men in Tokyo, Japan.

ABSTRACT: We report on hepatitis C virus genotype 2c infection in 12 human immunodeficiency virus-infected men who have sex with men in Tokyo, Japan. The uncommon strains from the 12 patients were genetically clustered; they suggested an emerging outbreak in this population at high risk of sexually transmitted infections.

Hemodialysis patients with coronavirus disease 2019: reduced antibody response.

BACKGROUND: Because patients on maintenance hemodialysis (HD) have an impaired immune response to pathogens, they are at higher risk of severe coronavirus disease 2019 (COVID-19). However, data on antibody production among HD patients with COVID-19 is scarce. Thus, we performed a retrospective cohort study evaluating severe acute respiratory syndrome coronavirus two antibody (SARS-CoV-2) production within 1 month after COVID-19 onset in hospitalized patients on HD. METHODS: SARS-CoV-2-specific immunoglobulin (Ig) G levels were quantified using an iFlash 3000 Chemiluminescence Immunoassay analyzer (Shenzhen YHLO Biotech Co., Ltd.) to detect IgG antibodies specific for the S1 subunit of the spike protein (IgG-S1). Propensity score matching was used to balance covariate distribution in HD and non-HD patients. From April 2020 to February 2021, antibody testing was performed on 161 hospitalized patients with symptomatic COVID-19. Of them, 34 HD patients were matched to 68 non-HD patients. RESULTS: After propensity score matching, the median levels of IgG-S1 in the HD patients at 7-13 days after symptom onset were significantly lower than in non-HD patients, especially in those with severe disease. Among all patients, those with severe disease produced lower levels of IgG-S1 at 7-13 days compared with non-severe patients. CONCLUSION: COVID-19 patients with severe disease, especially those undergoing HD, had lower IgG-S1 production in the second week of the disease. Thus, the increased risk of severe COVID-19 in HD patients may be, in part, due to a slow and reduced antibody response.

Disseminated Mycolicibacter arupensis and Mycobacterium avium co-infection in a patient with anti-interferon-γ neutralizing autoantibody-associated immunodeficiency syndrome.

BACKGROUND: Disseminated infections of Mycolicibacter arupensis, a slowly growing nontuberculous mycobacteria (NTM) which causes synovitis, osteomyelitis, or pulmonary infections have rarely been reported. We report a case of disseminated M. arupensis and Mycobacterium avium co-infection in a patient with anti-interferon (IFN)-γ neutralizing autoantibody-associated immunodeficiency syndrome. CASE PRESENTATION: A 68-year-old Japanese male without human immunodeficiency virus infection was referred with complaints of persistent low-grade fever, arthralgia of the upper limbs, and weight loss of 10 kg. Cervical and mediastinal lymphadenopathies as well as a nodular opacity in the right lung were detected, and biopsy specimens of the cervical lymph node yielded M. arupensis without evidence of malignant cells. M. arupensis was also detected in sputum and peripheral blood. Computed tomography (CT) revealed deterioration of the right supraclavicular lymphadenopathy with internal necrosis and multiple low-density splenic lesions. Bone marrow and aspirates from the cervical lymph node collected at initiation of treatment yielded M. avium. The presence of anti-IFN-γ neutralizing autoantibodies was detected, leading to a diagnosis of co-infection of M. arupensis and M. avium with anti-IFN-γ neutralizing autoantibody-associated immunodeficiency syndrome. Post initiation of treatment with clarithromycin, ethambutol, and rifabutin, his fever declined, and his polyarthritis resolved. He developed disseminated varicella zoster during treatment; however, a follow-up CT scan six months after treatment revealed improvement of the lymphadenopathies, consolidation in the right lung, and splenic lesions. CONCLUSION: This is the first report of disseminated M. arupensis and M. avium co-infection in a patient with anti-IFN-γ neutralizing autoantibody-associated immunodeficiency syndrome.

Outcomes associated with treatment change from tenofovir disoproxil fumarate to tenofovir alafenamide in HIV-1-infected patients: a real-world study in Japan.

OBJECTIVES: To investigate the impact of switching from tenofovir disoproxil fumarate (TDF)- to tenofovir alafenamide (TAF)-containing regimens on bone, kidney, serum lipids and body weight among Asian patients. METHODS: A prospective, multicentre, observational cohort study was conducted at three centres for HIV infection in Japan during 2017-2019. HIV-infected adults previously treated with TDF-containing regimens and scheduled to switch to TAF-containing regimens were included. Bone mineral density (BMD), renal markers, lipids and weight were measured consecutively from 12 months before to 12 months after the switch. RESULTS: Among 118 patients evaluated, the mean percentage change to spine BMD during 1 year of TAF treatment was higher than that during 1 year of TDF treatment (mean difference = 1.9%; 95% confidence interval (CI): 0.8-3.1). Urine protein and ß2 -microglobulin levels decreased significantly after the switch, while low-density lipoprotein cholesterol and triglycerides increased. During the TDF and TAF periods, the mean weight gains were 0.2 and 1.9 kg, respectively (mean difference = 1.6 kg; 95% CI: 0.9-2.3). Subgroup analysis revealed a significant difference between the mean body weight change associated with an integrase inhibitor (INSTI) (+2.8 kg) and that associated with a non-INSTI (+1.2 kg) third agent treatment only during the TAF period. CONCLUSIONS: Among predominantly Japanese HIV-infected patients, BMD and renal tubular markers improved, while lipid profiles worsened significantly after the switch. Weight gain during the TAF period was larger than that during the TDF period. Concurrent use of INSTI with TAF may act synergistically to gain body weight.

A nosocomial cluster of Roseomonas mucosa bacteremia possibly linked to contaminated hospital environment.

Roseomonas, a genus of pink-pigmented glucose non-fermentative bacteria, has been associated with various primary and hospital-acquired human infections; however, to our knowledge, its nosocomial transmission has never been reported. Clinical and epidemiological investigations were carried out after two cases of R. mucosa bacteremia occurred in our hospital in 2018. Environmental samples were taken of environmental surfaces prone to water contamination in the wards and cultured. The two clinical isolates and all environmental isolates that showed growth of pink colonies were identified using matrix-assisted laser desorption/ionization time of flight mass spectrometry and 16S rRNA gene sequencing. Pulse-field gel electrophoresis (PFGE) was performed and fingerprinting software was used to analyze the DNA restriction patterns and determine their similarity. Two patients who developed R. mucosa bacteremia had received care from the same treatment team. Of 126 environmental samples, five showed growth of R. mucosa. Using 80% similarity as the cut-off, PFGE analysis revealed that the isolates from the two patients' blood cultures and three environmental isolates belonged to the same clone. The hospital water environment was contaminated with the same clone of R. mucosa that caused bacteremia in the two patients, suggesting nosocomial transmission linked to contaminated environment. Increased vigilance is needed to monitor the emergence of Roseomonas in healthcare settings.

Association between length of residence and prevalence of MRSA colonization among residents in geriatric long-term care facilities.

BACKGROUND: A high prevalence of methicillin-resistant Staphylococcus aureus (MRSA) colonization has been reported among residents in geriatric long-term care facilities (LTCFs). Some studies indicate that MRSA might be imported from hospitals into LTCFs via resident transfer; however, other studies report that high MRSA prevalence might be caused by cross-transmission inside LTCFs. We aimed to assess which factors have a large impact on the high MRSA prevalence among residents of geriatric LTCFs. METHODS: We conducted a cohort study among 260 residents of four geriatric LTCFs in Japan. Dividing participants into two cohorts, we separately analyzed (1) the association between prevalence of MRSA carriage and length of LTCF residence (Cohort 1: n = 204), and (2) proportion of residents identified as MRSA negative who were initially tested at admission but subsequently identified as positive in secondary testing performed at ≥2 months after their initial test (Cohort 2: n = 79). RESULTS: Among 204 residents in Cohort 1, 20 (9.8%) were identified as positive for MRSA. Compared with residents identified as MRSA negative, a larger proportion of MRSA-positive residents had shorter periods of residence from the initial admission (median length of residence: 5.5 vs. 2.8 months), although this difference was not statistically significant (p = 0.084). Among 79 residents in Cohort 2, 60 (75.9%) were identified as MRSA negative at the initial testing. Of these 60 residents, only one (1.7%) had subsequent positive conversion in secondary MRSA testing. In contrast, among 19 residents identified as MRSA positive in the initial testing, 10 (52.6%) were negative in secondary testing. CONCLUSIONS: The prevalence of MRSA was lower among residents with longer periods of LTCF residence than among those with shorter periods. Furthermore, few residents were found to become MRSA carrier after their initial admission. These findings highlight that MRSA in LTCFs might be associated with resident transfer rather than spread via cross-transmission inside LTCFs.

Utility of Ascitic Fluid Adenosine Deaminase Levels in the Diagnosis of Tuberculous Peritonitis in General Medical Practice.

BACKGROUND: Tuberculous peritonitis is difficult to diagnose due to its varying clinical features, in addition to the low yield on bacterial culture or polymerase chain reaction using ascitic fluid samples. This study aimed to investigate the sensitivity and specificity of elevated adenosine deaminase (ADA) levels as a diagnostic marker for tuberculous peritonitis. METHODS: A retrospective cohort of 181 adult patients who underwent ascitic fluid ADA level examination at Jichi Medical University Hospital between January 2006 and December 2015 were included. We collected data regarding ascitic fluid analyses including ADA levels, bacteriology and cytology, final diagnosis (cause of ascites), basis of the diagnosis, duration to diagnosis, and disease outcome. RESULTS: Among 181 patients, elevated ascitic ADA levels (≥40 IU/L) were observed in 15 patients (median, 87.2 IU/L; range, 44.0-176.1 IU/L); 8 patients had tuberculous peritonitis, 4 had lymphoma-related ascites, and 2,had peritoneal carcinomatosis with bacterial coinfection, and 1 had chlamydial pelvic inflammatory disease. Among 166 patients without ascitic ADA level elevation (median, 7.3 IU/L; range, <2.0-39.1 IU/L), none had tuberculosis, 4 had lymphoma-related ascites, 28 had cancer/mesothelioma-related ascites, and 134 had ascites due to other causes. In our cohort, elevated ascitic fluid ADA levels (≥40 IU/L) showed 100% sensitivity, 96.0% specificity, 53.3% positive predictive value (PPV), and 100% negative predictive value for the diagnosis of peritoneal tuberculosis. CONCLUSIONS: Ascitic fluid ADA levels ≥40 IU/L showed excellent sensitivity, despite a low PPV, for the diagnosis of tuberculous peritonitis. Lymphoma-related ascites is an important mimic of tuberculous peritonitis that can result in high ascitic fluid ADA levels with similar clinical manifestations.

Histological evidence for the cardiac safety of high-dose pegylated liposomal doxorubicin in a patient with HIV-associated Kaposi sarcoma: a case report and literature review.

BACKGROUND: Pegylated liposomal doxorubicin plays an important role in the treatment of patients with severe refractory human immunodeficiency virus (HIV)-associated Kaposi sarcoma (KS). High cumulative doses of conventional doxorubicin exceeding 500 mg/m2 are known to cause cardiac toxicity. However, the safe cumulative dose of pegylated liposomal doxorubicin is unclear. CASE PRESENTATION: A 40-year-old Japanese man with HIV infection presented with pain, edema, and multiple skin nodules on both legs which worsened over several months. He was diagnosed with HIV-associated KS. He received long-term pegylated liposomal doxorubicin combined with antiretroviral therapy for advanced, progressive KS. The cumulative dose of pegylated liposomal doxorubicin reached 980 mg/m2. The patient's left ventricular ejection fraction remained unchanged from baseline during treatment. After he died as a result of cachexia and wasting, caused by recurrent sepsis and advanced KS, an autopsy specimen of his heart revealed little or no evidence of histological cardiac damage. We also conducted a literature review focusing on histological changes of the myocardium in patients treated with a cumulative dose of pegylated liposomal doxorubicin exceeding 500 mg/m2. CONCLUSIONS: This case report and literature review suggest that high (> 500 mg/m2) cumulative doses of pegylated liposomal doxorubicin may be used without significant histological/clinical cardiac toxicity in patients with HIV-associated KS.

Azithromycin plus ß-lactam versus levofloxacin plus ß-lactam for severe community-acquired pneumonia: A retrospective nationwide database analysis.

Previous studies showed potential benefits of macrolide combined with ß-lactam for severe community-acquired pneumonia (CAP). However, it remains inconclusive whether macrolide plus ß-lactam is superior to respiratory fluoroquinolone plus ß-lactam for patients with severe CAP. Using a nationwide inpatient database in Japan, we performed propensity score matching and inverse probability of treatment weighting (IPTW) to compare 28-day mortality and in-hospital mortality between azithromycin plus ß-lactam and levofloxacin plus ß-lactam for severe CAP patients admitted to hospital between July 2010 and March 2015. We identified 1,999 patients with severe pneumonia who received azithromycin plus ß-lactam (n = 840) or levofloxacin plus ß-lactam (n = 1,159) within 2 days after admission. Five-hundred sixty propensity score-matched pairs showed no significant differences between azithromycin plus ß-lactam and levofloxacin plus ß-lactam in 28-day mortality and in-hospital mortality (19.3% vs. 20.7%, p = 0.601 and 24.8% vs. 26.8%, p = 0.495, respectively). IPTW analysis also showed no significant differences between azithromycin plus ß-lactam and levofloxacin plus ß-lactam in 28-day mortality (risk difference, -3.5% [95% confidence interval, -8.8% to 1.7%] and in-hospital mortality (risk difference, -3.6%; 95% confidence interval, -9.4% to 2.1%). In conclusion, there were no significant differences in 28-day mortality and in-hospital mortality between azithromycin plus ß-lactam and levofloxacin plus ß-lactam for severe CAP patients.

Nasal diphtheria (chronic carriage) caused by nontoxigenic Corynebacterium diphtheriae.

Toxigenic strains of Corynebacterium diphtheriae cause the majority of respiratory diphtheria cases. However, nontoxigenic strains of C. diphtheriae can also cause diseases, and have become increasingly common. Infection that is limited to the anterior nares (nasal diphtheria) is a well-described but rare condition, even for toxigenic C. diphtheriae. We report a case involving chronic carriage of nasal diphtheria caused by nontoxigenic C. diphtheriae, as well as a review of other reported nontoxigenic C. diphtheriae cases in Japan. Mild or asymptomatic nasal diphtheria involving nontoxigenic strains, which can be the source of transmission, may be underrecognized. Our case highlights the importance of awareness regarding nontoxigenic diphtheria among clinicians, especially in the era of improved diphtheria vaccination coverage.

False-positive elevation of 1,3-beta-D-glucan caused by continuous administration of penicillin G.

The 1,3-beta-D-Glucan (BDG) assay is widely used for the diagnosis of fungal infections, especially in patients with hematologic malignancies. Some antimicrobials have been reported to cause false-positive results for BDG, but there has been no report on the effect of penicillin G (PCG) on BDG levels. We experienced a patient who developed false-positive BDG elevation during the administration of PCG for osteomyelitis due to Streptococcus pneumoniae infection. The serum BDG level increased up to 81.0 pg/ml during the continuous administration of PCG at 24 million units per day. However, chest and paranasal CT scan showed no evidence of fungal infection. The BDG level decreased to 38.0 pg/ml at 14 hours after the discontinuation of PCG. The amount of BDG in one vial of PCG inferred from these serum BDG levels is very similar to the actual BDG concentration in a vial of PCG. Therefore, during the administration of PCG, elevated BDG levels should be interpreted with caution, as they may be false-positive results.

Antimicrobial susceptibility testing of rapidly growing mycobacteria isolated in Japan.

BACKGROUND: Difficult-to-treat infections caused by rapidly growing mycobacteria (RGM) are increasingly observed in clinical settings. However, studies on antimicrobial susceptibilities and effective treatments against RGM in Japan are limited. METHODS: We conducted susceptibility testing of potential antimicrobial agents, including tigecycline and tebipenem, against RGM. Clinical RGM isolates were collected from a university hospital in Japan between December 2010 and August 2013. They were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and the sequencing of 16S rRNA, rpoB, and hsp65 genes. The samples were utilized for susceptibility testing using 16 antimicrobials, with frozen broth microdilution panels. RESULTS: Forty-two isolates were obtained: 13, Mycobacterium abscessus complex; 12, Mycobacterium chelonae; 9, Mycobacterium fortuitum; and 8, M. fortuitum group species other than M. fortuitum. Different antimicrobial susceptibility patterns were observed between RGM species. Clarithromycin-susceptible strain rates were determined to be 0, 62, and 100% for M. fortuitum, M. abscessus complex, and M. chelonae, respectively. M. abscessus complex (100%) and >80% M. chelonae isolates were non-susceptible, while 100% M. fortuitum group isolates were susceptible to moxifloxacin. Linezolid showed good activity against 77% M. abscessus complex, 89% M. fortuitum, and 100% M. chelonae isolates. Regardless of species, all tested isolates were inhibited by tigecycline at very low minimal inhibitory concentrations (MICs) of ≤0.5 µg/mL. MICs of tebipenem, an oral carbapenem, were ≤4 µg/mL against all M. fortuitum group isolates. CONCLUSIONS: Our study demonstrates the importance of correct identification and antimicrobial susceptibility testing, including the testing of potential new agents, in the management of RGM infections.

Dose-dependent artificial prolongation of prothrombin time by interaction between daptomycin and test reagents in patients receiving warfarin: a prospective in vivo clinical study.

BACKGROUND: Daptomycin has been reported to cause artificial prolongation of prothrombin time (PT) by interacting with some test reagents of PT. This prolongation was particularly prominent with high concentrations of daptomycin in vitro. However, whether this prolongation is important in clinical settings and the optimal timing to assess PT remain unclear. METHODS: A prospective clinical study was conducted with patients who received daptomycin for confirmed or suspected drug-resistant, gram-positive bacterial infection at a university hospital in Japan. PT at the peak and trough of daptomycin was tested using nine PT reagents. Linear regression analyses were used to examine the difference in daptomycin concentration and the relative change of PT-international normalized ratios (PT-INR). RESULTS: Thirty-five patients received daptomycin (6 mg/kg). The mean ± standard deviation of the trough and peak concentrations of daptomycin were 13.5 ± 6.3 and 55.1 ± 16.9 µg/mL, respectively. Twelve patients (34%) received warfarin. With five PT reagents, a significant proportion of participants experienced prolongation of PT-INR at the daptomycin peak concentration compared to the PT-INR at the trough, although the mean relative change was less than 10%. None of the participants clinically showed any signs of bleeding. A linear, dose-dependent prolongation of PT was observed for one reagent [unadjusted coefficient ß 3.1 × 10-3/µg/mL; 95% confidence interval (CI) 2.3 × 10-5-6.3 × 10-3; p = 0.048]. When patients were stratified based on warfarin use, this significant linear relationship was observed in warfarin users for two PT reagents (adjusted coefficient ß, 6.4 × 10-3/µg/mL; 95% CI 3.5 × 10-3-9.3 × 10-3; p < 0.001; and adjusted coefficient ß, 8.3 × 10-3/µg/mL; 95% CI 4.4 × 10-3-1.2 × 10-2; p < 0.001). In non-warfarin users, this linear relationship was not observed for any PT reagents. CONCLUSIONS: We found that a higher concentration of daptomycin could lead to artificial prolongation of PT-INR by interacting with some PT reagents. This change may not be clinically negligible, especially in warfarin users receiving a high dose of daptomycin. It may be better to measure PT at the trough rather than at the peak daptomycin concentration.

Cutaneous invasive aspergillosis in a patient with glioblastoma receiving long-term temozolomide and corticosteroid therapy.

Glioblastoma is an aggressive brain tumor that requires multidisciplinary treatment including adjuvant radiotherapy, chemotherapy, and adjunct corticosteroids. Temozolomide is a commonly used chemotherapy drug and frequently causes lymphocytopenia. We describe the case of a 67-year-old woman with cutaneous invasive aspergillosis who had received long-term temozolomide and corticosteroid therapy for glioblastoma. She presented with multiple indurations, erythema, and purpura, some of which produced purulent discharge, in the anterior abdomen. Extensive intra- or inter-muscular abscesses of the right anterior abdominal wall were also observed. Her absolute lymphocyte counts were 156/µL on admission. Cultures obtained from the wound yielded Aspergillus fumigatus. She was diagnosed with secondary cutaneous invasive aspergillosis, which likely resulted from hematogenous dissemination. Although rare, this case illustrates that temozolomide-induced lymphocytopenia, especially in cases of concomitant corticosteroid use, can be associated with severe invasive aspergillosis.

Development of cryptococcal immune reconstitution inflammatory syndrome 41 months after the initiation of antiretroviral therapy in an AIDS patient.

Cryptococcal meningitis is one of the most lethal fungal infections in patients with acquired immune deficiency syndrome (AIDS). The incidence of and mortality from cryptococcal meningitis have markedly decreased since the introduction of combination antiretroviral therapy (cART). However, despite its benefits, the initiation of cART results in immune reconstitution inflammatory syndrome (IRIS) in some patients. Although IRIS is occasionally difficult to distinguish from relapse or treatment failure, the distinction is important because IRIS requires a different treatment. Here, we present the case of a patient with AIDS who developed symptoms of cryptococcal IRIS 41 months after starting cART. To the best of our knowledge, the time between cART initiation and the onset of cryptococcal IRIS in this patient is the longest that has been reported in the literature.