Clinical and bacterial features of Group B streptococci with reduced penicillin susceptibility from respiratory specimens: a case-control study.

Streptococcus agalactiae (Group B Streptococcus, GBS) is an invasive pathogen that causes sepsis and meningitis among infants, elderly adults, and immunosuppressed patients. Generally, GBS is susceptible to penicillin; however, GBS with reduced penicillin susceptibility (PRGBS) has been reported. PRGBS are commonly isolated from respiratory specimens, but clinical features of patients with PRGBS remain unclear. In this case-control study, clinical features of patients with PRGBS and bacterial characteristics of these isolates from respiratory specimens were investigated. Patients with GBS at the University of the Ryukyus Hospital between January 2017 and June 2018 were retrospectively investigated. GBS were further classified into penicillin-susceptible GBS (PSGBS) and PRGBS using a drug susceptibility test. Moreover, serotypes, genotypes, and drug resistance genes of PRGBS isolates were determined. In total, 362 GBS were isolated, of which 46 were collected from respiratory specimens, which had the highest rate of PRGBS (24%). Compared to patients with PSGBS, those with PRGBS were more likely to have neuromuscular disease, poor performance status, risk of multidrug-resistant pathogen infection, prior pneumonia history within 1 year, and prior penicillin use within 1 year. Among eight PRGBS isolates, multilocus sequence typing revealed that five isolates were sequence type (ST) 358, two were ST3 and ST10, respectively, and one isolate was ST1404. All PRGBS isolates belonged to the ST1/ST19/ST10 group. This study reveals clinical characteristics of patients with PRGBS from respiratory specimens. Because invasive GBS infection cases are increasing, especially in the elderly, more attention should be paid to this infection.

Revised hospital antibiotic formulary reduces antimicrobial consumption and promotes a shift towards narrow-spectrum antibiotic usage.

BACKGROUND: In Japan, the national action plan to adress antimicrobial resistance problems aimed to reduce the use of oral cephalosporins, quinolones, and macrolides per day per 1000 inhabitants by 50% from the levelin 2013 by 2020. The aim of this study was to evaluate the effects of a revised antibiotic formulary on in- and out-hospital oral antibiotic prescribing practices at a 600-bed university hospital. METHOD: A retrospective before-and-after comparison study was conducted. All antimicrobial consumption data in the reviewed classes from 1 January 2013 to 31 December 2018, were extracted from the hospital database's electronic medical records. The data were measured in the defined daily dose and antibiotic use density (defined daily dose per 1000 patient-days). RESULTS: The total oral antibiotic use densities for in-hospital prescriptions in 2013 and 2018 were 117.95 and 75.42, respectively, and 239.83 and 193.88, respectively, for out-hospital prescriptions. From 2013 to 2018, antibiotic use densities of second- and third-generation cephalosporins, macrolides and fluoroquinolones for in-hospital prescriptions changed annually by -49.00%, -92.67%, +0.49% and -48.19%, and out-hospital prescriptions of these antibiotics changed by +76.69%, -86.37%, -16.29% and -51.75%, over the same period. Penicillin prescriptions increased by 71.31% for in-hospital and 42.72% for out-hospital prescriptions over this period. CONCLUSIONS: The revised hospital antibiotic formulary reduced total antibiotic consumption and increased the use of narrow-spectrum antibiotics for both in- and out-hospital prescriptions.

Brevibacterium paucivorans bacteremia: case report and review of the literature.

BACKGROUND: Brevibacteria are obligate aerobic gram-positive rods that are associated with milk products and are also found on human skin. Brevibacterium has been reported as a rare cause of catheter related blood steam infection mainly in immunocompromised hosts such as malignancies or AIDS patients. CASE PRESENTATION: A 94-year old woman, which had a past history of diabetes mellitus and chronic heart failure, presented with high fever associated with decreased oral intake and appetite loss and was admitted to our institute. A physical examination at the time of presentation was unremarkable. On day 2, both blood cultures collected on admission became positive with coryneform organism within 24 h without Staphylococci and Brevibacterium species were identified by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Subsequently, genetic investigation by 16S ribosomal RNA analysis was performed in order to identify the organism. Finally, the result identified this pathogen as Brevibacterium paucivorans with 99.5% homology on the Ez taxon database. The patient was started empirically on meropenem and teicoplanin for broad-spectrum antibiotic coverage. The patient's fever finally abated and labs were also improved. On day 14, the antibiotic therapy was discontinued. The site of infections was unknown. We hereby report a case of Brevibacterium paicivorans bacteremia in an immunocompetent patient and review cases of Brevibacterium specises bacteremia previously reported. This is the first case of B. paucivorans bacteremia as far as we could search. CONCLUSION: Physicians and microbiologists should be aware that Brevibacteria are uncommon but important agents which could cause opportunistic infections in immunocompetent.

Infective endocarditis caused by Cardiobacterium hominis endocarditis: A case report and review of the literature.

BACKGROUND: While it has been increasing cases of C. hominis endocarditis in the past decades due to advances of diagnostic methods, the epidemiology and clinical manifestations of IE caused by C. hominis is still unknown. CASE PRESENTATION: A 62-year old man was admitted to our institute with fever, anorexia and general fatigue for the preceding one month. He had a past medical history of both aortic and mitral valves replacement due to cardiac diseases. He was diagnosed as IE caused by C. hominis according to the modified duke criteria. The patient received 2 weeks of combination therapy of intravenous ceftriaxone (CTRX) 2g and gentamycin 180mg daily followed by 4 weeks CTRX 2g daily alone. Oral moxifloxacin 400mg once daily was given for an additional 4 weeks. After the antibiotic therapy was discontinued, disease recurrence was not observed. We reviewed previously reported C. hominis IE cases in 60 publications including ours. Of 73 patients enrolled, 53 were male, the mean age was 52 years. The most common risk factor of IE was past history of cardiac diseases in 44/73 (60%). As for antibiotics initially prescribed, third-generation cephalosporins was most frequently used in 28/69 (41%). While the cure rate was 67/73 (93%), 31/73 patients (43%) received a surgical intervention. Embolic lesions to the central nervous system and vertebrae were seen in 16/72 (22%) and 5/72 (7%). CONCLUSION: IE caused by C. hominis has a favorable prognosis, showing the cure rate of 93%. Physicians should recognize the possible occurrence of emboli among IE patients.

Considerations about the Use of a Loading Dose of Daptomycin in a Neutropenic Murine Thigh Infection Model with Methicillin-Resistant Staphylococcus aureus Infection.

Previous clinical studies have showed the clinical benefits of the initiation of treatment with a daptomycin (DAP) loading dose, but only a few studies have evaluated its antimicrobial benefits. We evaluated the efficacy of a DAP loading dose against methicillin-resistant Staphylococcus aureus (MRSA) infections in a neutropenic murine thigh infection model. Three MRSA isolates (DAP MIC: 0.5, 1, and 2 mg/L) were tested. Four DAP regimens simulating human concentration-time profiles, i.e., (i) day 1: 8 mg/kg and day 2: 6 mg/kg, (ii) days 1 and 2: 6 mg/kg/day, (iii) day 1: 8 mg/kg and day 2: 4 mg/kg, and (iv) days 1 and 2: 4 mg/kg/day, were administered to the mice. Efficacy was calculated as the change in bacterial density. DAP loading-dose regimen iii showed greater antimicrobial activity against MRSA with MIC 1 mg/L than nonloading regimen iv (-3.10 ± 0.63 vs. -0.71 ± 0.34 log10 CFU; p < 0.01). Loading-dose regimen iii achieved greater log10 CFU changes than nonloading regimen ii, while the total DAP dose for 2 days was the same (-3.10 ± 0.63 vs. -1.46 ± 0.48 log10 CFU; p < 0.05). DAP loading-dose regimen iii showed enhanced antimicrobial activity against MRSA with DAP MIC 0.5 mg/L when compared with nonloading regimen iv. However, loading-dose regimens i and iii did not reduce bacterial density for MRSA with DAP MIC 2 mg/L. Our data suggest that a DAP loading-dose regimen would be an advantageous procedure for patients infected with MRSA with DAP MIC ≤1 mg/L.

Comparative study on safety of linezolid and vancomycin in the treatment of infants and neonates for Gram-positive bacterial infections.

BACKGROUND: Vancomycin has been the common antimicrobial treatment for Gram-positive infection even in neonates and infants, while it is difficult to adjust blood concentration. Linezolid is also effective for Gram-positive infection, and is not necessary to monitor drug blood concentration. Primary objective of this study was to compare the safety of linezolid and vancomycin in infants and neonates for resistant Gram-positive infections. METHODS: In total, 68 patients [linezolid group (32 patients); vancomycin group (36 patients)] treated with antimicrobials at Aichi Medical University Hospital between April 2014 and March 2017. Investigation items were as follows; sex, age, gestational age, birth weight, body weight, duration of treatment, Apgar score, laboratory data, rate of patients with blood transfusion, serum levels of vancomycin, disease type, concomitant medications, clinical isolates, adverse effects during antimicrobial treatment, antimicrobial susceptibility of isolated Gram-positive bacteria. RESULTS: Any substantially abnormal laboratory values were admitted in linezolid 40.6% (13/32) and vancomycin 41.7% (15/36) groups, respectively (p = 0.93). Platelet count was significantly decreased in only linezolid group (p = 0.03). Any adverse events during antimicrobial treatment were admitted in linezolid 46.9% (15/32) and vancomycin 58.3% (21/36) groups, respectively (p = 0.34). CONCLUSION: There were no notable differences in safety of linezolid and vancomycin groups even in neonates and infants. However, platelet count was significantly decreased in only linezolid group. The careful monitoring of platelet count would be required for infants and neonates receiving linezolid treatment.

The epidemiology and risk factor of carbapenem-resistant enterobacteriaceae colonization and infections: Case control study in a single institute in Japan.

INTRODUCTION: While the emergence and spread of carbapenem-resistant enterobacteriaceae (CRE) carriage and infections are serious threats to public health worldwide, its prevalence and epidemiology are still unknown. METHODS AND PATIENTS: For the purpose of examining the prevalence, patients' background and risk factors for CRE carriage and infections, we conducted this case-control study. We retrospectively reviewed all patients isolating CRE at Aichi Medical University hospital from January 2010 until March 2017. The patients isolated with carbapenem-susceptible enterobacteriaceae (CSE) were randomly selected during the study period. RESULTS: A total of 26 patients, isolating 28 CRE infections were enrolled in this study. The detection rate of CRE carriage and infection was 0.22% (28/12,600). Compared to the CSE group, the CRE group had poorer PS and higher CCI scores. The CRE group tended to stay longer in hospital (121 v.s. 63 days, p = 0.052) and admission fee was much more expensive than CSE group (220,710 v.s. 69,904 JPY, p < 0.001). PS 2-4 (ECOG) and CCI≧3 (p = 0.002), prior hospitalization within 90 days (p = 0.006) and prior antibiotics use within 90 days (p = 0.005) were risk factors for acquisition of CRE by univariate analysis. The combination of PS 2-4 and CCI≧3 was an independent risk factor for CRE carriage and infection by multivariate logistic regression analysis. CONCLUSION: The combination of PS 2-4 (ECOG) and CCI score≧3 was an independent risk factor of CRE carriage and infections. The CRE group tended to stay longer in hospital, and the medical expense was much more expensive than those in the CSE group.

Rituximab Restores IFN-γ-STAT1 Function and Ameliorates Disseminated Mycobacterium avium Infection in a Patient with Anti-Interferon-γ Autoantibody.

A 67-year-old Japanese female with back pain and severe cachexia visited our hospital. The diagnosis was disseminated Mycobacterium avium complex infection (dMAC) with multiple bone involvement. Anti-mycobacterial chemotherapy was started, but fever persisted and dislocation of cervical vertebrae has made her bedridden. Because anti-interferon (IFN)-γ autoantibody was positive, four doses of rituximab 375 mg/m2, every 7 day, were administered. Soon after treatment, progression of osteolytic lesions and wasting has stopped. We proved that rituximab has recovered IFN-γ signaling as shown by IFN-γ-induced STAT1 phosphorylation. It can be a promising option for dMAC cases with anti-IFN-γ autoantibody.

Secondary organizing pneumonia following viral pneumonia caused by severe influenza B: a case report and literature reviews.

BACKGROUND: Some reported that organizing pneumonia (OP) may occur after influenza A infections including swine-origin influenza A (H1N1). However, OP associated with influenza B infection has never been reported. We report the first case of secondary OP associated with viral pneumonia caused by influenza B. CASE PRESENTATION: A 23-year old woman was diagnosed as viral pneumonia caused by type B influenza. Despite of antiviral therapy, abnormal chest shadows were not improved. Bronchoscopy and transbronchial lung biopsy showed organizing pneumonia due to viral pneumonia caused by influenza B. Corticosteroid therapy was started at 30 mg daily (0.5 mg/kg), and the dose was reduced to 25, 20, 15 or 10 mg per day every month with symptomatic and radiological resolution. Even after corticosteroid therapy was discontinued, we did not confirm disease recurrence. CONCLUSIONS: Physicians should be aware of the possibility for SOP and severe viral pneumonia even in case of type B as well as type A influenza infections.

In vitro and in vivo Pharmacodynamics of Colistin and Aztreonam Alone and in Combination against Multidrug-Resistant Pseudomonas aeruginosa.

BACKGROUND: Reports of Pseudomonas aeruginosa with high antimicrobial resistance have steadily emerged, threatening the utility of a mainstay in antipseudomonal therapy. This study evaluated the antimicrobial activities of various combination therapies against P. aeruginosa with high antimicrobial resistance, including multidrug-resistant P. aeruginosa (MDRP) using an in vitro and in vivo study. METHODS: We evaluated 24 combination therapies, including colistin, aztreonam, meropenem, ceftazidime, ciprofloxacin, amikacin, rifampicin, arbekacin and piperacillin against 15 MDRP isolates detected at Aichi Medical University Hospital with the break-point checkerboard method. Based on the results of the in vitro study, we evaluated antimicrobial activity against highly antimicrobial-resistant P. aeruginosa with an in vivo murine thigh infection model. RESULTS: The combination regimens including colistin and aztreonam showed higher antimicrobial activity against the 15 MDRP isolates. In the in vivo study, the high-dose colistin monotherapy (16 mg/kg every 12 h) achieved greater log10 CFU changes than the normal-dose colistin regimen (8 mg/kg every 12 h) against 5 P. aeruginosa isolates, including 2 MDRP isolates (p < 0.05). Aztreonam monotherapy (400 mg every 8 h) yielded bacterial densities similar to untreated control mice for the MDRP isolate evaluated. The combination therapy with a higher dose of colistin had superior antimicrobial activity against 5 P. aeruginosa with colistin (MIC 0.5 µg/ml) and aztreonam (MIC ≥128 µg/ml) than colistin monotherapy. CONCLUSION: The data suggest that the combination treatment of colistin and aztreonam could be the most useful for treating highly resistant P. aeruginosa with a higher susceptibility to colistin, including MDRP infections.

Assessment of optimal initial dosing regimen with vancomycin pharmacokinetics model in very low birth weight neonates.

INTRODUCTION: Pharmacokinetic of vancomycin in very low birth weight neonates showed big variety, and limited data were available due to very minor population. These facts make it difficult to adjust its optimal initial dosage. Therefore, this study was to develop optimal dosing regimen of vancomycin in very low birth weight neonates. METHODS: Between 2010 and 2015, low birth weight neonates (≤1500 g) were included in a population pharmacokinetics analysis. Based on the pharmacokinetic parameters we estimated, we simulated individual blood concentrations of vancomycin and evaluated the probability of its pharmacokinetics/pharmacodynamics (PK/PD) target attainment, such as 24-h area under the concentration-time curve (AUC24)/MIC (≥400) and blood trough concentration (10-20 µg/mL), as primary measure for several dosing regimens by Monte Carlo simulation method. RESULTS: Ten patients were prescribed vancomycin and detected its blood concentrations as routine pharmacy practice to adjust the dosage. A one-compartment model was used and clearance significantly correlated with serum creatinine and the volume of infusion. In this model, vancomycin dose at 10 mg/kg three times a day (TID) was predicted to result 86.7% of neonates for an MIC of 1 µg/mL achieving AUC/MIC of ≥400 and 30.6% of the neonates for an MIC of 2 µg/mL. Moreover, the probability of reaching the target trough concentration was 70.5% for patients treated with vancomycin 10 mg/kg TID. DISCUSSION: We recommended vancomycin 10 mg/kg TID as initial dosage regimens for low birth weight neonates infected with the pathogens showed MIC of ≤1 µg/mL.

Clinical effectiveness of daptomycin loading dose in patients infected with Gram-positive pathogens.

This study was to evaluate the loading does of daptomycin, a novel lipopeptide antibacterial active against Gram-positive pathogens, on clinical efficiency. We divided patients received daptomycin therapy into 2 groups. One of two groups comprised patients received the loading dose of daptomycin on day 1 (group 1) and the other group received normal dosage (4-6 mg/kg/day) (group 2). Inflammatory markers were assessed at least 3 days before daptomycin therapy started as their baseline, and 2 weeks from daptomycin therapy started for the evaluation of clinical efficacy. The bacteriological results were also evaluated. The occurrence of creatinine kinase (CK) elevation was evaluated as side effect. As results, the only group 1 showed significant improvements in body temperature and CRP on 4-7 days after daptomycin therapy started, while 2 groups significantly improved in WBC, body temperature and CRP on 8-14 days, respectively. The group 1 showed early improvement of body temperature (<37.5 °C) on 4-7 days, compared with the group 2 (group 1; 3 [2-7], group 2; 6 [2-11], p = 0.01). The bacteriological cure rates in both groups showed high cure rates (group 1; 20/0, group 2; 27/3, p = 0.14). The frequency of CK elevation was 0% (0/22 patients) and 3.0% (1/33 patients) in group 1 and group 2, respectively. In our conclusion, daptomycin loading dose did not prove evident clinical effectiveness, compared with the regimen without loading dose. However, we could not disclaim the potential to improve clinical response early with DAP loading dose for critically ill patients.

The etiology and bacteriology of healthcare-associated empyema are quite different from those of community-acquired empyema.

OBJECTS: Changes in patients' background and life environment could contribute to increase healthcare-associated (HCA) empyema. There are no guidelines and statements for HCA empyema. METHODS: We retrospectively reviewed all patients with empyema who were admitted to the Aichi Medical University Hospital, Japan between 2008 and 2015. We evaluated patients' characteristics, microbial profiles, treatment and outcomes, and analyzed prognostic factors for 90-day mortality. RESULTS: A total of 48 patients were enrolled in this study. They were categorized into community-acquired (CA) empyema (16 patients) and healthcare-associated (HCA) empyema (32 patients). HCA empyema patients had higher Charlson comorbidity index (CCI) scores, and poorer performance status (PS) than CA empyema patients. Potentially-drug resistant (PDR) pathogens were seen more frequently in HCA empyema than in CA empyema. Compared with survival and death groups, the death group showed higher CCI scores and poorer PSs than the survival group. The death group had more malignancy than the survival group. PDR pathogens were detected more frequently in the death group than in the survival group. Multivariate analysis showed that emergence of PDR pathogens and malignancies were independent poor prognostic factors for 90-days mortality among empyema. CONCLUSION: The etiology and bacteriology of HCA empyema are quite different from those of CA empyema. Especially, the mortality of HCA empyema was higher than the one of CA empyema. Emergence of PDR pathogens in the pleural fluid detected by culture, pulmonary disease and malignancies were independent poor prognostic factors among CA and HCA empyema by multivariate logistic regression analysis.

Antimicrobial activity of fidaxomicin against Clostridium difficile clinical isolates in Aichi area in Japan.

We evaluated the susceptibility of 100 Japanese Clostridium difficile isolates to fidaxomicin, a new macrocyclic antibiotic. The minimum inhibitory concentration (MIC) range of fidaxomicin was 0.03-0.5 µg/mL, with a MIC for inhibition of 50% (MIC50) of 0.12 µg/mL, and for inhibition of 90% (MIC90) of 0.25 µg/mL. We also evaluated the susceptibilities of the same 100 C. difficile isolates to vancomycin, metronidazole, moxifloxacin, clindamycin, meropenem, and ampicillin. Of all the antibiotics tested, fidaxomicin showed the most potent antimicrobial activity against this group of C. difficile isolates. MIC levels against C. difficile isolates, including those producing binary toxin, did not substantially differ from those previously reported in Europe, North America and Taiwan.

Colistin loading dose enhanced antimicrobial activity for in vivo mouse thigh infection model with Pseudomonas aeruginosa with highly antimicrobial resistant.

This is the first report to test the loading dosage of colistin against Pseudomonas aeruginosa, including MDRP. Using in vivo murine thigh infection model, in the loading dosage regimen (Day 1:50 mg/kg q12 h, Day 2-3: 25 mg/kg q12 h) group, 5 to 6 log10 CFU/ml reduction compared with control were observed for both strains of P. aeruginosa with colistin MIC 0.5 and 1 µg/mL at 72 h. But, similar reduction was observed for the strains with colistin MIC 0.5 µg/mL only in normal dosage regimen (Day 1-3: 25 mg/kg q12 h) group. For P. aeruginosa with colistin MIC 1 µg/mL, colistin loading dosage regimens showed greater antimicrobial activity than that of without loading dosage group (p < 0.05). These data suggest that the colistin loading regimen would be one of the useful options for P. aeruginosa with antimicrobial resistance infection treatment.

Adverse events of prophylactic anti-influenza agents in medical staffs.

BACKGROUND: We undertook a survey to evaluate the compliance and the tolerability of oseltamivir and zanamivir when they were used as post-exposure prophylaxis among the medical staffs in the 2014-2015 seasons to understand a characteristic of adverse events caused by anti-influenza (flu) agents. MATERIALS AND METHODS: During the study period, 540 medical staffs received oseltamivir (75 mg twice a day for 5 days) or zanamivir (twice a day for 5 days) as post-exposure prophylaxis of influenza, respectively. RESULTS: Four hundred eleven medical staffs of 540 medical staffs (76.1%) provided responses to questionnaire investigations. The adverse events caused by oseltamivir were reported by 86 of 382 medical staffs (22.5%). The most frequent adverse events were gastrointestinal adverse events (13.4%), followed by systemic and local diseases (11.8%), diseases of the nervous system (7.9%) and neuropsychiatric adverse events (0.5%). On the other hand, adverse events caused by zanamivir were reported by one (3.4%) of 29 medical staffs. CONCLUSION: Our survey revealed that 22.5% subjects experienced any adverse events due to oseltamivir. And the regimen showed low compliance than we expected. On the other hands, zanamivir showed high adherence with lower incidence of adverse events.

Evaluation of commercial phenotypic assays for the detection of IMP- or New Delhi metallo-ß-lactamase-producing Enterobacteriaceae isolates in Japan.

OBJECTIVES: This study was designed to evaluate the sodium mercaptoacetic acid double disk synergy test (SMA-DDST), the Etest metallo-ß-lactamase (MBL) MP/MPI (Etest MP/MPI), and the Mastdiscs ID Carbapenemase Detection Disc Set (MAST-CDS) for the detection of MBL-producing Enterobacteriaceae isolates in Japan. METHODS: Fifty-one clinical isolates and four reference strains were tested. These isolates included 40, 4, and 11 IMP-, New Delhi MBL (NDM)-, and non-MBL-producers, respectively. SMA-DDST was performed with meropenem (MEPM)-containing disks. RESULTS: Sensitivities were 38/44 (86%), 40/44 (91%), and 15/44 (34%), and the cost ratio was 1:9.4:3.8 for MEPM-SMA-DDST:Etest MP/MPI:MAST-CDS, respectively. The specificity was 11/11 (100%) for all assays. MEPM-SMA-DDST detected IMP-producing isolates with high sensitivity (38/40; 95%), but the assay was inadequate for NDM-producing isolates (0/4; 0%). The Etest MP/MPI detected both IMP- (36/40; 90%) and NDM-producing isolates (4/4; 100%), but was the most expensive. MAST-CDS detected IMP-producing isolates with low sensitivity (11/40; 28%), but the assay worked well for NDM-producing isolates (4/4; 100%). CONCLUSIONS: Our results indicated that MEPM-SMA-DDST was the most cost-effective assay for the detection of IMP-producing isolates. Therefore, we conclude that MEPM-SMA-DDST is the optimal available assay for clinical first-line screening in IMP-endemic areas such as Japan. However, this assay could not detect NDM-producing isolates, whereas the Etest MP/MPI and MAST-CDS could. When MEPM-SMA-DDST is negative, the Etest MP/MPI and MAST-CDS could be used to obtain supportive data and prevent detection failure for NDM-producing isolates.

Caspofungin versus micafungin in the incidence of hepatotoxicity in patients with normal to moderate liver failure.

BACKGROUND: One of the major adverse events of caspofungin and micafungin is hepatotoxicity, however, there are few reports compared the incidence of hepatotoxicity between caspofungin and micafungin. Herein, the primary objective of this study was to compare the incidence of hepatotoxicity between caspofungin and micafungin treatments for patients with fungal or suspected fungal infection. METHODS: In total, 201 patients [caspofungin group: 66 patients; micafungin group: 135 patients] treated with echinocandins from April 2014 to November 2015 at Aichi Medical University Hospital. Investigation item were as follows; sex, age, weight, height, duration of treatment, total dose, disease type, clinical isolates, liver enzyme levels, concomitant medications. Liver function was assessed in accordance with Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0. We divided into two groups depend on their liver enzyme levels before treated with echinocandins; normal group (liver enzyme levels ≤ CTCAE Grade 1), abnormal group (liver enzyme levels ≥ CTCAE Grade 2). RESULTS: The overall incidence of serious hepatotoxicity (Grade 3 or higher) was 6.1% (4/66) in the caspofungin group and 7.4% (10/135) in the micafungin group. The proportion of patients used caspofungin and micafungin showed serious hepatotoxicity were 0% (0/47) and 6.5% (7/108) in normal group (p = 0.17), and 21.1% (4/19) and 10.7% (3/28) in abnormal group (p = 0.42). CONCLUSION: There was no notable difference in serious hepatotoxicity between the caspofungin group and the micafungin group, even though in patients with abnormal liver enzyme levels (CTCAE grade 2 or higher).

Efficacy of tedizolid against methicillin-resistant Staphylococcus aureus and Peptostreptococcus anaerobius in thigh mixed-infection mouse model.

OBJECTIVE: The purpose of this study is to compare the antimicrobial activity of human simulated exposures of tedizolid 200 mg daily, and linezolid 600 mg every 12 h for the treatment of complicated skin and skin structure infection (cSSSI) caused by MRSA and Peptostreptococcus anaerobius in both the neutropenic mice thigh mixed-infection models. MATERIAL AND METHOD: Tedizolid phosphate and linezolid were used for all in vivo testing. A total of one MRSA and two P. anaerobius isolates were utilized. Antimicrobial efficacy was calculated for each isolate as the change in bacterial numbers (Δlog10 CFU/ml) obtained in the treated mice after 24 h compared with the numbers in the starting control animals (0 h). RESULTS: The tedizolid and linezolid MICs for MRSA was 0.25 and 2 µg/ml. Tedizolid MIC for P. anaerobius was 0.12 µg/ml, and linezolid MICs for two P. anaerobius isolates were 0.5 and 1 µg/ml. In mixed infection model, tedizolid therapy showed similar antimicrobial activities for one MRSA and two P. anaerobius isolates evaluated, compared with linezolid therapy. Additionally, when comparing the activity of tedizolid and linezolid monotherapy between single infection and mixed infection model, antimicrobial activities of both antimicrobials were attenuated when mixed infection model was used. CONCLUSION: In the neutropenic murine thigh infection model, human simulated exposures of tedizolid and linezolid resulted in similar efficacies against MRSA, even though single and mixed infection models were used. These data support the clinical utility of tedizolid for use against MRSA and P. anaerobius in the treatment of cSSSI.