Daisuke Sakanashi

Evaluation of commercial phenotypic assays for the detection of IMP- or New Delhi metallo-β-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-β-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.

Eosinophilic pneumonia caused by daptomycin: Six cases from two institutions and a review of the literature

Here we report six cases of daptomycin (DAP)-induced eosinophilic pneumonia (DIEP) encountered at two medical centers and present a review of 43 DIEP patients from 26 studies to compare the clinical characteristics and radiographic findings of acute and chronic eosinophilic pneumonia (AEP; CEP). Four of the six patients did not exhibit respiratory symptoms, and one patient with only fever was misdiagnosed with DAP-induced fever. According to our literature review and the present findings, male sex and old age were dominant risk factors for DIEP. Fever and fine crackles were the most common clinical manifestations. The DAP dose and duration of administration were not significant risk factors for DIEP, and we also could not find any association between allergic predisposition and DIEP. Among the reviewed patients, 51.8% did not show more than 25% eosinophils in bronchoalveolar lavage, which is a criterion for the diagnosis of drug-induced eosinophilic pneumonia. Chest images of all patients showed CEP patterns such as multiple reticulonodular infiltrates in the subpleural region and diffuse bilateral pulmonary infiltrates with ground-glass opacities. However, 66.7% of patients also exhibited pleural effusion, a feature specific to AEP. All patients showed prompt recovery after DAP withdrawal. Our results suggest that clinicians should consider DIEP as a differential diagnosis when patients receiving DAP therapy, particularly men and elderly patients, present with fever, even in the absence of respiratory symptoms. Furthermore, they should be aware that the occurrence of DIEP is independent of the DAP dose and administration duration, and allergic reaction.

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.

The Prophylactic Effect of Anti-influenza Agents for an Influenza Outbreak in a University Hospital

Objective From November 24 to December 9, 2013, an outbreak of the influenza (flu) A (H3) virus occurred in a tertiary-care university hospital (1,014 beds). We herein report the prophylactic effect of anti-flu agents for controlling the flu outbreak. Methods We administered pre- or post-exposure prophylaxis with anti-flu agents in flu outbreak. To test the effectiveness of prophylaxis in a flu outbreak, we used the posterior mean of the reproductive value during the pre- and post-intervention period. We also simulated the probability distribution of new flu cases. We performed an analysis to quantify the strength of the intervention effect. Results A total of 97 people were diagnosed with flu before the intervention, and 7 were diagnosed after the intervention. A molecular analysis of the flu virus revealed that this outbreak was due to the flu A (H3) virus. A total of 3,702 people received prophylaxis. There was a significant reduction in the reproductive value from 1.89 [95% confidence interval (CI), 1.59 to 2.24] to 0.65 (95% CI, 0.02 to 1.00) after the intervention (p<0.001). Conclusion Prophylaxis with anti-flu agents, along with prompt identification and isolation of infected individuals, was effective in reducing the impact of a flu outbreak in a hospital.