Cryptogenic invasive Klebsiella pneumoniae liver abscess syndrome

SummaryBackgroundKlebsiella pneumoniae-associated liver abscesses have distinct clinical and epidemiologic features.MethodsWe report the unusual case of an American patient with a K. pneumoniae-associated liver abscess and septic spread to other organs. We additionally present a comprehensive review of K. pneumoniae-associated liver abscess syndromes in adults.ResultsWe identified three distinct K. pneumoniae liver abscess syndromes: the polymicrobial liver abscess, the monomicrobial cryptogenic noninvasive liver abscess, and the monomicrobial cryptogenic invasive K. pneumoniae-associated liver abscess (CIKPLA) syndromes, with distinct clinical, epidemiologic and outcome features. CIKPLA syndrome typically affects diabetic patients, mainly in Southeast Asia, and is complicated by septic spread to other organs.ConclusionsThe community-acquired, monomicrobial, K. pneumoniae-associated liver abscess syndromes that typically occur in the USA are mainly noninvasive and affect Asian or Hispanic persons. However, this report provides an alert that CIKPLA syndrome can occur in North America, and physicians need to be aware of it

90Y-clivatuzumab tetraxetan with or without low-dose gemcitabine: A phase Ib study in patients with metastatic pancreatic cancer after two or more prior therapies

AbstractBackgroundFor patients with metastatic pancreatic adenocarcinoma, there are no approved or established treatments beyond the 2nd line. A Phase Ib study of fractionated radioimmunotherapy was undertaken in this setting, administering 90Y-clivatuzumab tetraxetan (yttrium-90-radiolabelled humanised antibody targeting pancreatic adenocarcinoma mucin) with or without low radiosensitising doses of gemcitabine.MethodsFifty-eight patients with three (2–7) median prior treatments were treated on Arm A (N=29, 90Y-clivatuzumab tetraxetan, weekly 6.5mCi/m2doses×3, plus gemcitabine, weekly 200mg/m2 doses×4 starting 1week earlier) or Arm B (N=29, 90Y-clivatuzumab tetraxetan alone, weekly 6.5mCi/m2doses×3), repeating cycles after 4-week delays. Safety was the primary endpoint; efficacy was also evaluated.ResultsCytopaenias (predominantly transient thrombocytopenia) were the only significant toxicities. Fifty-three patients (27 Arm A, 26 Arm B, 91% overall) completed ⩾1 full treatment cycles, with 23 (12 Arm A, 11 Arm B; 40%) receiving multiple cycles, including seven (6 Arm A, 1 Arm B; 12%) given 3–9 cycles. Two patients in Arm A had partial responses by RECIST criteria. Kaplan–Meier overall survival (OS) appeared improved in Arm A versus B (hazard ratio [HR] 0.55, 95% CI: 0.29–0.86; P=0.017, log-rank) and the median OS for Arm A versus Arm B increased to 7.9 versus 3.4months with multiple cycles (HR 0.32, P=0.004), including three patients in Arm A surviving >1year.ConclusionsClinical studies of 90Y-clivatuzumab tetraxetan combined with low-dose gemcitabine appear feasible in metastatic pancreatic cancer patients beyond 2nd line and a Phase III trial of this combination is now underway in this setting