Raoultella ornithinolytica is a Gram-negative aerobic bacillus reclassified in the new genus from the Klebsiella species based on new genetic approaches; however, human infections caused by R. ornithinolytica are rare. We herein report three cases of R. ornithinolytica bacteremia associated with biliary tract infections in cancer patients. R. ornithinolytica can be a causative pathogen of biliary tract infection in cancer patients.

The treatment for anaplastic lymphoma kinase (ALK)‐positive lung cancer has been rapidly evolving since the introduction of several ALK tyrosine kinase inhibitors (ALK‐TKI) in clinical practice. However, the acquired resistance to these drugs has become an important issue. In this study, we collected a total of 112 serial biopsy samples from 32 patients with ALK‐positive lung cancer during multiple ALK‐TKI treatments to reveal the resistance mechanisms to ALK‐TKI. Among 32 patients, 24 patients received more than two ALK‐TKI. Secondary mutations were observed in 8 of 12 specimens after crizotinib failure (G1202R, G1269A, I1171T, L1196M, C1156Y and F1245V). After alectinib failure, G1202R and I1171N mutations were detected in 7 of 15 specimens. G1202R, F1174V and G1202R, and P‐gp overexpression were observed in 3 of 7 samples after ceritinib treatment. L1196M + G1202R, a compound mutation, was detected in 1 specimen after lorlatinib treatment. ALK‐TKI treatment duration was longer in the on‐target treatment group than that in the off‐target group (13.0 vs 1.2 months). In conclusion, resistance to ALK‐TKI based on secondary mutation in this study was similar to that in previous reports, except for crizotinib resistance. Understanding the appropriate treatment matching resistance mechanisms contributes to the efficacy of multiple ALK‐TKI treatment strategies.

Shikonin derivatives are red naphthoquinone pigments produced by several boraginaceous plants, such as Lithospermum erythrorhizon. These compounds are biosynthesized from p-hydroxybenzoic acid and geranyl diphosphate. The coupling reaction that yields m-geranyl-p-hydroxybenzoic acid has been actively characterized, but little is known about later biosynthetic reactions. Although 3"-hydroxy-geranylhydroquinone produced from geranylhydroquinone by CYP76B74 has been regarded as an intermediate of shikonin derivatives, the next intermediate has not yet been identified. This study describes a novel alcohol dehydrogenase activity in L. erythrorhizon cell cultures. This enzyme was shown to oxidize the 3"-alcoholic group of (Z)-3"-hydroxy-geranylhydroquinone to an aldehyde moiety concomitant with the isomerization at the C2'-C3' double bond from the Z-form to the E-form. An enzyme oxidizing this substrate was not detected in other plant cell cultures, suggesting that this enzyme is specific to L. erythrorhizon. The reaction product, (E)-3"-oxo-geranylhydroquinone, was further converted to deoxyshikonofuran, another meroterpenoid metabolite produced in L. erythrorhizon cells. Although non-enzymatic cyclization occurred slowly, it was more efficient in the presence of crude enzymes of L. erythrorhizon cells. This activity was detected in both shikonin producing and non-producing cells, suggesting that the aldehyde intermediate at the biosynthetic branch point between naphthalene and benzo/hydroquinone ring formation likely constitutes a key common intermediate in the synthesis of shikonin and benzoquinone products, respectively.

Background Anaplastic lymphoma kinase (ALK) fusion genes are found in 3%–5% of non‐small cell lung cancers (NSCLCs). ALK inhibitors show a very high response rate to ALK‐positive NSCLCs. However, the emergence of acquired resistance is inevitable. In this study, we investigated the drugs for overcoming resistance especially compound mutations after sequential treatment with crizotinib, alectinib, and lorlatinib. Method Next‐generation sequencing (NGS) and Sanger sequencing were performed on a liver biopsy tissue obtained from a clinical case. Ba/F3 cells in which mutant EML4‐ALK were overexpressed were prepared, and cell viability assay and immunoblotting were performed to check the sensitivity of five independent ALK inhibitors. Results I1171S + G1269A double mutation was identified by NGS and Sanger sequencing on a liver biopsy tissue from a patient who relapsed on lorlatinib treatment. Ceritinib and brigatinib—but not other ALK inhibitors—were active against the compound mutations in the cell line model. Conclusions With the sequential ALK inhibitors treatment, cancer cells accumulate new mutations in addition to mutations acquired previously. The identified compound mutation (I1171S + G1269A) was found to be sensitive to ceritinib and brigatinib, and indeed the patient's tumor partially responded to ceritinib. Key points ALK compound mutation was found in a clinical sample that was resistant to lorlatinib after sequential ALK‐tyrosine kinase inhibitor (TKI) treatment. Ceritinib and brigatinib are potential overcoming drugs against ALK I1171S + G1269A double mutation.

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Our study and other smaller ones suggest that lymphocyst infections following pelvic lymphadenectomy for malignant gynecologic tumors usually are monomicrobial and caused by gram-positive cocci, including Staphylococcus, Streptococcus, and Enterococcus, and anaerobes such as Bacteroides fragilis. These bacteria should be considered when selecting empiric antibiotic therapy.

Helicobacter fennelliae is a gram-negative, spiral bacillus that appears as thin-spread colonies on sheep blood agar and is similar to Helicobacter cinaedi. H fennelliae is diagnosed by genetic testing, which is not readily available in all laboratories. Therefore, H fennelliae bacteremia has only been reported sporadically, and little is known about its clinical characteristics.We describe 3 cases of H fennelliae bacteremia with gastrointestinal symptoms, including nausea, vomiting, and diarrhea. Isolates could be differentiated from H cinaedi by biochemical reaction testing, including nitrate reduction and alkaline phosphatase hydrolysis.We retrospectively reviewed 24 cases of H fennelliae bacteremia reported in the literature. Most of the patients had immunosuppressive backgrounds, including solid tumors, hematological malignancies, and autoimmune diseases. Although gastrointestinal symptoms were common, cellulitis was not often observed in patients with H fennelliae bacteremia.Clinicians should bear in mind that H fennelliae may be a differential diagnosis in patients with gastrointestinal manifestations and gram-negative, spiral bacilli. In addition, biochemical reactions, such as nitrate reduction and alkaline phosphatase hydrolysis, are useful in differentiating H fennelliae from H cinaedi.

This report describes a case of Cryptococcus gattii VGIIb infection of the pulmonary and central nervous systems in an immunocompetent Japanese man with a travel history, and it hypothesizes the place where he was infected with C. gattii using the genotype information.