Discovery of a new antifungal agent ASP2397 using a silkworm model of Aspergillus fumigatus infection
The Journal of Antibiotics advance online publication, August 31 2016. doi:10.1038/ja.2016.106
Authors: Ikuko Nakamura, Ryuichi Kanasaki, Koji Yoshikawa, Shigetada Furukawa, Akihiko Fujie, Hiroshi Hamamoto & Kazuhisa Sekimizu
In silico identification of lysocin biosynthetic gene cluster from Lysobacter sp. RH2180-5
The Journal of Antibiotics advance online publication, August 24 2016. doi:10.1038/ja.2016.102
Authors: Suresh Panthee, Hiroshi Hamamoto, Yutaka Suzuki & Kazuhisa Sekimizu
Antibiotics are among the most important interventions in healthcare. Resistance of bacteria to antibiotics threatens the effectiveness of treatment. Systematic reviews of antibiotic treatments often do not address resistance to antibiotics even when data are available in the original studies. This omission creates a skewed view, which emphasizes short-term efficacy and ignores the long-term consequences to the patient and other people. We offer a framework for addressing antibiotic resistance in systematic reviews. We suggest that the data on background resistance in the original trials should be reported and taken into account when interpreting results. Data on emergence of resistance (whether in the body reservoirs or in the bacteria causing infection) are important outcomes. Emergence of resistance should be taken into account when interpreting the evidence on antibiotic treatment in randomized controlled trials or systematic reviews.
Antimicrobial chemotherapy now spans 80 years and four generations. The healthcare epidemiologist has an important role to play in this field. Efforts focus in three areas: (i) minimizing the transmission of antimicrobial-resistant bacteria in healthcare settings (infection control); (ii) optimizing use of currently available antibacterial drugs (antibiotic stewardship); and (iii) recognizing and responding to opportunities for new drug development. For each area, the epidemiologist provides data that address four practical questions—‘What is the problem?’, ‘What should be done?’, ‘Is it being done?’ and ‘Is it working?’. A team approach is crucial to acting on the epidemiological data. Examples are presented to illustrate different roles of the epidemiologist, and tools and measures that have been developed to address some problems of current importance. Monitoring of quality, integrity and security of data remains a major focus. The epidemiologist will continue to have a key role in antimicrobial chemotherapy.
Pneumocystis jirovecii can cause life-threatening pneumonia following treatment for haematological malignancies or after HSCT. The mortality rate of P. jirovecii pneumonia (PCP) in these patients is 30%–60%, especially after HSCT. The clinical presentation of PCP in haematology differs from that associated with HIV infection, with the disease being acute and more often severe, having a lower fungal burden and being more frequently linked to treatment with corticosteroids. Most cases occur in patients not receiving adequate prophylaxis. The development of new therapies, including targeted treatments and monoclonal antibodies in various haematological diseases, justifies constant vigilance in order to identify new at-risk populations and give prophylaxis accordingly. The fifth and sixth European Conferences on Infections in Leukaemia (ECIL-5 and ECIL-6) aimed to review risk factors for PCP in haematology patients and to establish evidence-based recommendations for PCP diagnosis, prophylaxis and treatment. This article focuses on the magnitude of the problem, the main differences in clinical presentation between haematology patients and other immunocompromised populations, especially HIV-infected patients, and the main risk factors.
The 5th European Conference on Infections in Leukaemia (ECIL-5) meeting aimed to establish evidence-based recommendations for the prophylaxis of Pneumocystis jirovecii pneumonia (PCP) in non-HIV-infected patients with an underlying haematological condition, including allogeneic HSCT recipients. Recommendations were based on the grading system of the IDSA. Trimethoprim/sulfamethoxazole given 2–3 times weekly is the drug of choice for the primary prophylaxis of PCP in adults (A-II) and children (A-I) and should be given during the entire period at risk. Recent data indicate that children may benefit equally from a once-weekly regimen (B-II). All other drugs, including pentamidine, atovaquone and dapsone, are considered second-line alternatives when trimethoprim/sulfamethoxazole is poorly tolerated or contraindicated. The main indications of PCP prophylaxis are ALL, allogeneic HSCT, treatment with alemtuzumab, fludarabine/cyclophosphamide/rituximab combinations, >4 weeks of treatment with corticosteroids and well-defined primary immune deficiencies in children. Additional indications are proposed depending on the treatment regimen.
The initiation of systemic antimicrobial treatment of Pneumocystis jirovecii pneumonia (PCP) is triggered by clinical signs and symptoms, typical radiological and occasionally laboratory findings in patients at risk of this infection. Diagnostic proof by bronchoalveolar lavage should not delay the start of treatment. Most patients with haematological malignancies present with a severe PCP; therefore, antimicrobial therapy should be started intravenously. High-dose trimethoprim/sulfamethoxazole is the treatment of choice. In patients with documented intolerance to this regimen, the preferred alternative is the combination of primaquine plus clindamycin. Treatment success should be first evaluated after 1 week, and in case of clinical non-response, pulmonary CT scan and bronchoalveolar lavage should be repeated to look for secondary or co-infections. Treatment duration typically is 3 weeks and secondary anti-PCP prophylaxis is indicated in all patients thereafter. In patients with critical respiratory failure, non-invasive ventilation is not significantly superior to intubation and mechanical ventilation. The administration of glucocorticoids must be decided on a case-by-case basis.
Activity of tick antimicrobial peptide from Ixodes persulcatus (persulcatusin) against cell membranes of drug-resistant Staphylococcus aureus
The Journal of Antibiotics advance online publication, August 17 2016. doi:10.1038/ja.2016.101
Authors: Naruhide Miyoshi, Emiko Isogai, Keiichi Hiramatsu & Takashi Sasaki
Vestaines, novel vasoactive compounds, isolated from Streptomyces sp. SANK 63697
The Journal of Antibiotics advance online publication, August 17 2016. doi:10.1038/ja.2016.98
Authors: Yuki Hirota-Takahata, Emi Kurosawa, Yoko Ishimoto, Yuko Iwadate, Masaaki Kizuka, Jun Chiba, Toru Hasegawa, Masahiro Tanaka & Hideki Kobayashi
Germicidins H–J from Streptomyces sp. CB00361
The Journal of Antibiotics advance online publication, August 10 2016. doi:10.1038/ja.2016.100
Authors: Ming Ma, Mostafa E Rateb, Dong Yang, Jeffrey D Rudolf, Xiangcheng Zhu, Yong Huang, Li-Xing Zhao, Yi Jiang, Yanwen Duan & Ben Shen
CD101, a novel echinocandin with exceptional stability properties and enhanced aqueous solubility
The Journal of Antibiotics advance online publication, August 10 2016. doi:10.1038/ja.2016.89
Authors: B Radha Krishnan, Kenneth D James, Karen Polowy, B J Bryant, Anu Vaidya, Steve Smith & Christopher P Laudeman
Allantopyrone A activates Keap1–Nrf2 pathway and protects PC12 cells from oxidative stress-induced cell death
The Journal of Antibiotics advance online publication, August 10 2016. doi:10.1038/ja.2016.99
Authors: Shota Uesugi, Makoto Muroi, Yasumitsu Kondoh, Yoshihito Shiono, Hiroyuki Osada & Ken-ichi Kimura
