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Introduction: Recently, complicated intra-abdominal infections (cIAI) have been caused not only by Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, and Pseudomonas aeruginosa, but also by extended-spectrum β-lactamase-producing Enterobacterales members. Ceftolozane–tazobactam (CTLZ–TAZ) is considered to exhibit therapeutic effects against cIAI. Studies on the concentrations of antibiotics in abdominal tissues directly affected by cIAI are limited. Therefore, in this study, we investigated the pharmacokinetics of CTLZ–TAZ in abdominal tissue and simulated the administration regimen required to achieve the pharmacodynamic target for cIAI-causing bacteria. Methods: Patients scheduled for elective lower gastrointestinal surgery were intravenously administered preoperative CTLZ–TAZ (1 g CTLZ and 0.5 g TAZ). Plasma, peritoneal fluid, peritoneum, and subcutaneous adipose tissue samples were collected during the surgery, and CTLZ as well as TAZ concentrations were measured. The noncompartmental and compartmental pharmacokinetic parameters were then estimated. Site-specific pharmacodynamic target attainment analysis using 1.5 g of CTLZ–TAZ was performed. Results: CTLZ–TAZ was administered to nine patients (once to five patients and twice to four patients). The mean peritoneal fluid-to-plasma ratio (one dose/two doses) for CTLZ was 0.74/1.15, which was slightly higher than the mean peritoneal fluid-to-plasma ratio for TAZ (0.95/1.13). The ratio for subcutaneous adipose was lower than those for peritoneal fluid and peritoneum tissues. We also discovered that the average ratio of CTLZ and TAZ concentrations in all tissues was maintained at or above 2:1. In our investigation of pharmacodynamic target attainment in each tissue, the desired bactericidal effect was attained with all CTLZ–TAZ (1.5 g) administration regimens [q12h (3 g/day), q8h (4.5 g/day), and q6h (6 g/day)]. Conclusion: To the best of our knowledge, this is the first study investigating the optimal pharmacodynamic level of CTLZ–TAZ in the abdominal tissue against cIAI-causing bacteria. This study also serves as a guideline for designing an optimal administration regimen based on pharmacodynamic target attainment for cIAI-causing bacteria. Details of the trial registration: The institutional review board of Hiroshima University Hospital, CRB6180006. The Japan Registry of Clinical Trials, jRCTs061190025.

ABSTRACTWe determined the complete nucleotide sequence of a self-transmissible IncL/M plasmid, pKOI-34, from a Klebsiella oxytocaisolate. pKOI-34 possessed the core structure of an IncL/M plasmid found in Erwinia amylovora, pEL60, with two mobile elements inserted, a transposon carrying the arsenic resistance operon and a Tn21-like core module (tnpand mermodules) piggybacking blaIMP-34as a class 1 integron, In808, where blaIMP-34confers a resistance to carbapenems in K. oxytocaand Klebsiella pneumoniae.

We report 2 cases of ulcerative colitis (UC) with intestinal tract dilatation treated with tacrolimus. They were 53- and 64-year-old males, who had been admitted to local hospitals for increasing severity of their UC symptoms. Treatment for severe UC was immediately started, but both cases were refractory to corticosteroid therapy; they were then transferred to our hospital. When they were referred to our hospital, they had frequent bloody diarrhea, fever, severe abdominal pain, and even dilatation of the transverse colon on abdominal X-ray test. They were treated with oral tacrolimus medication, and their symptoms improved immediately. Dilatation of the transverse colon was improved on plain X-ray at 2 weeks after starting therapy, and emergency colectomy could be avoided. These 2 cases may suggest that tacrolimus is effective for UC with colonic dilatation as a rescue therapy.

ABSTRACTA 9-year surveillance for multidrug-resistant (MDR) Pseudomonas aeruginosain the Hiroshima region showed that the number of isolates harboring the metallo-β-lactamase gene blaIMP-1abruptly increased after 2004, recorded the highest peak in 2006, and showed a tendency to decline afterwards, indicating a history of an epidemic. PCR mapping of the variable regions of the integrons showed that this epidemic was caused by the clonal persistence and propagation of an MDR P. aeruginosastrain harboring the blaIMP-1gene and an aminoglycoside 6′-N-acetyltransferase gene, aac(6′)-Iaein a class I integron (In113), whose integrase gene intl1was disrupted by an IS26insertion. Sequence analysis of the representative strain PA058447 resistance element containing the In113-derived gene cassette array showed that the element forms an IS26transposon embedded in the chromosome. It has a Tn21backbone and is composed of two segments sandwiched by three IS26s. In Japan, clonal nationwide expansion of an MDR P. aeruginosaNCGM2.S1 harboring chromosomally encoded In113 with intact intl1is reported. Multilocus sequence typing and genomic comparison strongly suggest that PA058447 and NCGM2.S1 belong to the same clonal lineage. Moreover, the structures of the resistance element in the two strains are very similar, but the sites of insertion into the chromosome are different. Based on tagging information of the IS26present in both resistance elements, we suggest that the MDR P. aeruginosaclone causing the epidemic in Hiroshima for the past 9 years originated from a common ancestor genome of PA058447 and NCGM2.S1 through an IS26insertion into intl1of In113 and through IS26-mediated genomic rearrangements.

ABSTRACTWe have determined the DNA sequence of Klebsiella pneumoniaemultidrug resistance plasmid pKPI-6, which is a self-transmissible IncN-type plasmid. pKPI-6 harboring blaIMP-6and blaCTX-M-2confers a stealth-type carbapenem resistance phenotype on members of the family Enterobacteriaceaethat is not detectable with imipenem. pKPI-6 is already epidemic in Japan, favoring the dissemination of IMP-6 and CTX-M-2 in members of the family Enterobacteriaceae.

ABSTRACTKlebsiella pneumoniaeshowing high resistance to all ß-lactams except imipenem, designated as ISMRK (imipenem-susceptible meropenem-resistant Klebsiella) is emerging in Japan. The carbapenem resistance of ISMRK cannot be screened by the Vitek and the RAISUS rapid automated susceptibility test systems, which may lead to inappropriate antimicrobial therapy, resulting in compromised patient outcomes.