Clostridium butyricum-induced ω-3 fatty acid 18-HEPE elicits anti-influenza virus pneumonia effects through interferon-λ upregulation.

The precise mechanism by which butyrate-producing bacteria in the gut contribute to resistance to respiratory viral infections remains to be elucidated. Here, we describe a gut-lung axis mechanism and report that orally administered Clostridium butyricum (CB) enhances influenza virus infection resistance through upregulation of interferon (IFN)-λ in lung epithelial cells. Gut microbiome-induced ω-3 fatty acid 18-hydroxy eicosapentaenoic acid (18-HEPE) promotes IFN-λ production through the G protein-coupled receptor (GPR)120 and IFN regulatory factor (IRF)-1/-7 activations. CB promotes 18-HEPE production in the gut and enhances ω-3 fatty acid sensitivity in the lungs by promoting GPR120 expression. This study finds a gut-lung axis mechanism and provides insights into the treatments and prophylaxis for viral respiratory infections.

In vivo study assessed meropenem and amikacin combination therapy against carbapenem-resistant and carbapenemase-producing Enterobacteriaceae strains.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE), especially for carbapenemase-producing Enterobacteriaceae (CPE), is an emerging cause that pose a significant threat to public health. However, efficient therapy has not been established. We assessed the antimicrobial efficacy of meropenem (MEPM) and amikacin (AMK) combination therapy. MATERIAL AND METHODS: Total eight isolates of Escherichia coli or Klebsiella pneumoniae, including CRE and/or CPE have carbapenemase genes were used. The relationship between phenotype and in vivo efficacy was assessed in neutropenic murine thigh infection model. Efficacy was determined using the change in bacterial density and survival rate. RESULTS: The combination therapy showed enhanced antimicrobial activities against CRE+/CPE+ and CRE+/CPE-K. pneumoniae isolates than MEPM monotherapy (0.63 ± 0.04 vs. 2.56 ± 0.24 ⊿log10 cfu/mL, p < 0.05; -1.05 ± 0.15 vs. -0.48 ± 0.30 ⊿log10 cfu/mL, p < 0.05). Likewise, the combination therapy showed enhanced antimicrobial activities against CRE+/CPE+ and CRE+/CPE-E. coli isolates than MEPM monotherapy (0.90 ± 0.68 vs. 1.86 ± 0.23 ⊿log10 cfu/mL, p < 0.05; -1.81 ± 0.06 vs. -0.88 ± 0.23 ⊿log10 cfu/mL, p < 0.05). Also, combination therapy group showed similar to higher survival rates in CRE + E. coli infection mice, compared to MEPM monotherapy group. CONCLUSION: Our results are the first supportive data to threat CRE infections with combination therapy of MEPM and AMK with in vivo model. The current results verify the promising utility of the combination therapy with MEPM and AMK against CRE isolates with a wide range of MEPM MICs.

Effect of High Blood Glucose Level on the Antimicrobial Activity of Daptomycin against Staphylococcus aureus in Streptozotocin-Induced Diabetic Mice.

Daptomycin is active against Staphylococcus aureus including methicillin-resistant S. aureus (MRSA), demonstrating efficacy in the treatment of infections in diabetic patients. However, daptomycin degrades in 5% glucose solution, and data on the efficacy of daptomycin in hyperglycemic patients are limited. Therefore, we investigated the effect of high levels of blood glucose on the efficacy and concentration of daptomycin. The efficacy of simulated human exposure to daptomycin against S. aureus was compared in a neutropenic murine thigh model, with and without hyperglycemia. A clinically isolated MRSA strain and S. aureus ATCC25923 standard strain were used. Daptomycin concentrations, in the serum and at the infected site, were preliminarily analyzed using the high-performance liquid chromatography assay. Even in hyperglycemic mice, the mean concentration of daptomycin in hyperglycemic mice was equivalent to that in untreated mice within the physiological blood glucose levels. Additionally, the efficacy of daptomycin against MRSA was equal to that observed in the untreated and hyperglycemic mice. Based on similar studies using S. aureus ATCC25923, the efficacy in hyperglycemic mice was equal to or greater than that observed in untreated mice. In conclusion, daptomycin is an alternative therapeutic option in diabetic mice with serious staphylococcal infections, regardless of blood glucose control in this animal model.

Tradescantia pallida extract inhibits biofilm formation in Pseudomonas aeruginosa.

Pseudomonas aeruginosa is capable of biofilm formation. In this study, we investigated the effects of aqueous Tradescantia pallida extract on Pseudomonas aeruginosa growth and biofilm formation. Aqueous Tradescantia pallida extracts significantly inhibited both bacterial growth and biofilm formation. However, methanolic Tradescantia pallida extracts inhibited neither. Aqueous Tradescantia pallida extracts were deactivated by heating but were not deactivated by light exposure. The ingredients retained the inhibitory effect on the bacterial growth and biofilm formation after ultrafiltration of aqueous Tradescantia pallida extract. Furthermore, polyphenol-rich Tradescantia pallida extracts inhibited bacterial growth, thus, polyphenols are possible to be an active ingredient. We observed the biofilm by scanning electron microscopy, and quantitative and qualitative differences in the biofilm and cells morphology. Interestingly, the biofilm treated aqueous Tradescantia pallida extracts remained premature. We postulated that premature biofilm formation was due to the inhibition of swarming motility. Indeed, aqueous Tradescantia pallida extracts inhibited swarming motility. These results demonstrate that Peudomonas aeruginosa growth and biofilm formation are inhibited by aqueous Tradescantia pallida extracts.

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for clinical microbiology in 2014: General view of the pathogens' antibacterial susceptibility.

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2014. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between January 2014 and April 2015 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standards Institute. Susceptibility testing was evaluated in 1534 strains (335 Staphylococcus aureus, 264 Streptococcus pneumoniae, 29 Streptococcus pyogenes, 281 Haemophilus influenzae, 164 Moraxella catarrhalis, 207 Klebsiella pneumoniae, and 254 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 43.6%, and those of penicillin-susceptible S. pneumoniae was 100%. Among H. influenzae, 8.2% of them were found to be ß-lactamase-producing ampicillin-resistant strains, and 49.1% to be ß-lactamase-non-producing ampicillin-resistant strains. Extended spectrum ß-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo ß-lactamase were 9.2% and 0.4%, respectively.

Metronidazole-induced encephalopathy caused by hyperbaric oxygen therapy in a patient with mandibular osteomyelitis.

Metronidazole (MNZ) is prescribed for the treatment of infection caused by anaerobic bacteria and protozoa. Metronidazole-induced encephalopathy (MIE) has been known to be a side-effect, although its onset ratio is unclear. However, to the best of our knowledge, MIE associated with hyperbaric oxygen therapy (HBO) has not been previously reported. Here, we present the case of a 68-year-old man with mandibular osteomyelitis who received metronidazole for 49 days and received five times HBO therapy. He visited our hospital for evaluation and treatment of peripheral neuropathy, speech disturbance, nausea, and disturbance of gait after 47 days of initiating metronidazole treatment. Brain magnetic resonance imaging revealed hyperintense lesions in the cerebellar dentate nuclei, which was consistent with MIE. The patient's ataxic symptoms improved in 15 days after the discontinuation of MNZ. This is the first report demonstrating case of MIE could be related with HBO, as far as we had searched.

Antimicrobial activity of solithromycin and levofloxacin against a murine pneumonia mixed-infection model caused by Streptococcus pneumoniae and anaerobic bacteria.

INTRODUCTION: Solithromycin is a novel fluoroketolide developed to treat pneumonia. But, few studies evaluating its antimicrobial activity against S. pneumoniae in a mixed-infection model with anaerobes are available, while community-acquired pneumonia can involve mixed-infection of Streptococcus pneumoniae and anaerobic bacteria. This study evaluated the antimicrobial activity of solithromycin against macrolide-resistant S. pneumoniae and anaerobic bacteria with a murine pneumonia mixed-infection model. MATERIAL AND METHODS: We evaluated antimicrobial activity of solithromycin (10 and 20 mg/kg) and levofloxacin (126 mg/kg) against S. pneumoniae with a three-point mutation in penicillin-binding protein and an ermB gene, and Parvimonas micra. Antimicrobial efficacy was calculated for each isolate as the change in bacterial count (Δlog10 CFU/mL) obtained in the treated mice after 24 h compared with the count in the starting control animals. RESULTS: The solithromycin and levofloxacin minimum inhibitory concentrations (MICs) for S. pneumoniae were 0.03 and 0.5 µg/mL, respectively. The solithromycin and levofloxacin MICs for P. micra were 0.015 and 0.12 µg/mL, respectively. In a mixed-infection model, solithromycin showed significantly higher antimicrobial activity against S. pneumoniae than levofloxacin (solithromycin 20 mg/kg; -2.87 ± 1.33 log10 CFU/mL vs. levofloxacin; -1.35 ± 0.37 log10 CFU/mL, p = 0.0397). Similarly, solithromycin showed significantly higher antimicrobial activity against P. micra than levofloxacin (solithromycin 20 mg/kg; -2.78 ± 0.98 log10 CFU/mL vs. levofloxacin; -1.57 ± 0.47 log10 CFU/mL, p = 0.0400). DISCUSSION: Solithromycin showed higher antimicrobial activities against macrolide-resistant S. pneumoniae and P. micra than levofloxacin, even though they were coexisted in murine lung tissue. Our results suggest that solithromycin could be effective for pneumonia patients due to S. pneumoniae to reduce bacterial density in lung tissue.

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.

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.

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.

Proposed breakpoint of piperacillin/tazobactam against extended spectrum ß-lactamases producing bacteria in bacteremia.

The isolation rate of extended-spectrum ß-lactamase (ESBL)-producing bacteria have been increasing in Japan. While the efficacy of piperacillin/tazobactam (PIPC/TAZ) for ESBL-producing bacteria is controversial, carbapenems have generally been shown to be effective. The aim of this study was to determine whether the current Clinical and Laboratory Standards Institute susceptibility breakpoint of ≤16/4 µg/mL PIPC/TAZ predicts the clinical usefulness for bacteremia caused by ESBL-producing Enterobacteriaceae. We retrospectively investigated 35 patients with bacteremia caused by Enterobacteriaceae producing ESBLs treated with PIPC/TAZ monotherapy. The microbiological and clinical efficacy with PIPC/TAZ minimum inhibitory concentrations (MICs) of ≤16/4 µg/mL was better than that with MICs ≥ 32/4 µg/mL. In contrast, MICs ≤8/4 µg/mL showed significantly higher microbiological and clinical efficacy compared to that of MICs ≥16/4 µg/mL (P < 0.05). These results suggest that 8/4 µg/mL PIPC/TAZ MIC is recommended as a breakpoint for bacteremia caused by ESBL-producing Enterobacteriaceae in Japan, although the current CLSI breakpoint is also useful.

Antifungal susceptibilities of Candida species isolated from the patients with vaginal candidiasis.

There have been the current Japanese data on susceptibility testing for Candida isolates from vaginal candidiasis. The in vitro activities of therapeutic antifungal drugs for vulvovaginal candidiasis (VVC); miconazole (MCZ), itraconazole (ITCZ), fluconazole (FLCZ), clotrimazole (CTZ), oxiconazole (OCZ), isoconazole (ICZ) and bifonazole (BFZ) against vaginal isolates. Fifty-four strains Candida albicans and 19 strains of Candida glabrata were evaluated using a broth microdilution method specified by Clinical Laboratories Standard Institute (CLSI) document M27-A3. The MIC90 of each drug, MCZ, ITCZ, FLCZ, CTZ, OCZ, ICZ and BFZ, against C. albicans and C. glabrata isolates were 0.25, 0.12, 1, 0.06, 0.12, 0.12 and 1 µg/ml and 1, 1, 8, 0.5, 0.25, 0.5 and 1 µg/ml respectively. The activities of these drugs, except for BFZ, against C. glabrata were lower than that of C. albicans. There was one azole-resistant isolate in C. glabrata of which MIC of FLCZ is > 64 µg/ml and this isolate had cross resistance to other antifungal drugs tested. These results suggest that antifungal drugs for treatment of VVC continues to have potent antifungal activities against C. albicans and C. glabrata isolates from vaginitis. CTZ, OCZ and ICZ susceptibility of FLCZ low susceptibility C. glabrata are relatively higher than MCZ, ITCZ and FLCZ.

Characterization of Piperacillin/Tazobactam-Resistant Klebsiella oxytoca Recovered from a Nosocomial Outbreak.

We characterized 12 clinical isolates of Klebsiella oxytoca with the extended-spectrum ß-lactamase (ESBL) phenotype (high minimum inhibitory concentration [MIC] values of ceftriaxone) recovered over 9 months at a university hospital in Japan. To determine the clonality of the isolates, we used pulsed-field gel electrophoresis (PFGE), multi-locus sequence typing (MLST), and PCR analyses to detect blaRBI, which encodes the ß-lactamase RbiA, OXY-2-4 with overproduce-type promoter. Moreover, we performed the isoelectric focusing (IEF) of ß-lactamases, and the determination of the MICs of ß-lactams including piperacillin/tazobactam for 12 clinical isolates and E. coli HB101 with pKOB23, which contains blaRBI, by the agar dilution method. Finally, we performed the initial screening and phenotypic confirmatory tests for ESBLs. Each of the 12 clinical isolates had an identical PFGE pulsotype and MLST sequence type (ST9). All 12 clinical isolates harbored identical blaRBI. The IEF revealed that the clinical isolate produced only one ß-lactamase. E. coli HB101 (pKOB23) and all 12 isolates demonstrated equally resistance to piperacillin/tazobactam (MICs, >128 µg/ml). The phenotypic confirmatory test after the initial screening test for ESBLs can discriminate ß-lactamase RbiA-producing K. oxytoca from ß-lactamase CTX-M-producing K. oxytoca. Twelve clinical isolates of K. oxytoca, which were recovered from an outbreak at one university hospital, had identical genotypes and produced ß-lactamase RbiA that conferred resistance to piperacillin/tazobactam. In order to detect K. oxytoca isolates that produce RbiA to promote research concerning ß-lactamase RbiA-producing K. oxytoca, the phenotypic confirmatory test after the initial screening test for ESBLs would be useful.

Open-label study to evaluate the pharmacodynamics, clinical efficacy, and safety of meropenem for adult bacterial meningitis in Japan.

The aim of this study was to assess the efficacy, safety, and concentration of meropenem in cerebrospinal fluid when meropenem (2 g every 8 h) was administered to Japanese adult patients with bacterial meningitis. Five Japanese patients (mean age 60.6 years [range 35-71]) were enrolled. Infection with Streptococcus pneumoniae (three patients), Streptococcus salivarius (one patient), and Staphylococcus aureus (one patient) was confirmed by cerebrospinal fluid culture. Meropenem (2 g every 8 h) was administered to all five patients. Treatment duration ranged from 14 to 28 days (mean 22.6 days). All the patients were successfully treated. The concentration of meropenem in cerebrospinal fluid ranged from 0.27 to 6.40 µg/ml up to 8.47 h and was over 1 µg/ml 3 h after starting meropenem infusion. In each patient, the present study confirmed for the first time that the concentration of meropenem in cerebrospinal fluid exceeded the minimal inhibitory concentration for these pathogens. Eleven clinical and laboratory adverse events considered to be related to meropenem were observed in all patients, but no serious adverse event and no discontinuance of treatment due to adverse events occurred. Thus meropenem appeared to be a well-tolerated and effective agent for Japanese adult patients with bacterial meningitis. 2 g every 8 h of meropenem was delivered to CSF and its concentration was exceed in MICs for the detected pathogens.

[Clinical investigation of arbekacin sulfate based on Cmax/MIC].

We examined the peck concentration (Cmax)/minimal inhibitory concentration (MIC) and the clinical efficacy in methicillin-resistant Staphylococcus aureus (MRSA) pneumonia and Gram-positive cocci bacteremia. We evaluated arbekacin (ABK) on 22 cases of pneumonia and 10 cases of bacteremia in Aichi Medical University Hospital between August 2008 and July 2011, retrospectively. In pneumonia cases, Cmax/MIC was 16.4 +/- 2.8 in the effective group, and was 17.6 +/- 4.5 in the not effective group, the significant differences were not accepted (p = 0.8). The dosage of ABK was 4.7 +/- 1.4 mg/kg/dose in the effective group and was 4.3 +/- 0.7 mg/kg/dose in the not effective group. In bacteremia cases, Cmax/MIC was 24.2 +/- 13.9 in the effective group and 12.9 +/- 3.9 in the not effective group about clinical efficacy, and the high tendency was accepted by the effective group (p < 0.05). The dosage of ABK was 3.4 +/- 1.1 mg/kg/dose in the effective group, and 3.0 +/- 0.6 mg/kg/dose in the not effective group. In this examination, the significant difference was not observed in clinical efficacy and Cmax/MIC in the pneumonia cases. Although it was reported that clinical efficacy of ABK was given Cmax/MIC at eight or more, in this examination, all cases was eight or more at Cmax/MIC, and the clinical effect was 40.9%. On Cmax/MIC of ABK, clinical effective group was higher than not effective group in bacteremia cases, it was suggested that the administration design should make that Cmax/MIC at least about 14 or more would be necessary.

Antimicrobial efficacies of several antibiotics against uterine cervicitis caused by Mycoplasma genitalium.

Mycoplasma genitalium has been shown to be one of the pathogens responsible for uterine cervicitis by many studies. However, there are no clinical recommendations for treating M. genitalium-positive uterine cervicitis. Our study retrospectively investigated the antimicrobial efficacies of several antibiotics against uterine cervicitis caused by M. genitalium. We studied a total of 257 women with M. genitalium-positive uterine cervicitis, except for those with chlamydial and gonococcal infections, who were treated with one of the following antibacterial therapies: azithromycin extended release formulation (AZM-SR) 2 g single dose, azithromycin (AZM) 1 g single dose, clarithromycin (CAM) 400 mg/day for 7 days, CAM 400 mg/day for 14 days, moxifloxacin (MFLX) 400 mg/day for 7 days, MFLX 400 mg/day for 14 days, levofloxacin (LVFX) 500 mg/day for 7 days, LVFX 500 mg/day for 14 days, sitafloxacin (STFX) 200 mg/day for 7 days, and STFX 200 mg/day for 14 days. A PCR-based assay was performed to evaluate the microbiological efficacy of eradication in these patients. M. genitalium was eradicated from the uterine cervix in 19 of the 21 (90.5%) patients treated with AZM-SR 2 g single dose, in 38 of the 42 (90.5%) patients treated with MFLX 400 mg/day for 7 days, in 42 of the 42 (100%) patients treated with MFLX 400 mg/day for 14 days, and in 12 of the 13 (92.3%) patients treated with STFX 200 mg/day for 14 days. In conclusion, AZM-SR 2 g single dose, MFLX 400 mg/day for 14 days, and STFX 200 mg/day for 14 days would each be an effective treatment for M. genitalium infection.

[Antifungal susceptibility of Candida species isolated from patient with invasive fungal peritonitis and investigation on clinical breakpoints of itraconazole].

We investigated antifungal susceptibility of 96 Candida species strains (37 strains of Candida albicans, 30 of Candida glabrata, 16 of Candida tropicalis and 13 of Candida parapsilosis) isolated from patients with invasive fungal peritonitis. Antifungal activity showed micafungin (MCFG), voriconazole (VRCZ)>itraconazole (ITCZ)>fluconazole (FLCZ). Judged by clinical breakpoints of Clinical and Laboratory Standards Institute (CLSI), FLCZ-resistant C. albicans, ITCZ-resistant C. albicans and VRCZ-resistant C. albicans were detected in the frequency of 5.4% (2/37), 21.6% (8/37) and 5.4% (2/37), respectively. We also retrospectively investigated the association of both antifungal susceptibility judged by CLSI breakpoints and clinical efficacy in 16 patients with invasive fungal peritonitis treated by injectable ITCZ. Clinical success and failure were obtained in cases of ITCZ MIC < or = 1 microg/mL and > or = 4 microg/ml, respectively. We conclude that we should re-consider CLSI breakpoints on ITCZ.