Norifumi Shigemoto

Emergence in Japan of an imipenem-susceptible, meropenem-resistant Klebsiella pneumoniae carrying blaIMP-6.

We identified 5 Klebsiella pneumoniae isolates showing high resistance to β-lactams except imipenem and designated them ISMRK (imipenem-susceptible but meropenem-resistant Klebsiella). They carried the bla(IMP-6) and bla(CTX-M-2) on a self-transmissible plasmid. ISMRK may be falsely categorized as susceptible to carbapenems if imipenem is used to screen carbapenem resistance.

Complete Nucleotide Sequence of the IncN Plasmid Encoding IMP-6 and CTX-M-2 from Emerging Carbapenem-Resistant Enterobacteriaceae in Japan

ABSTRACT We have determined the DNA sequence of Klebsiella pneumoniae multidrug resistance plasmid pKPI-6, which is a self-transmissible IncN-type plasmid. pKPI-6 harboring blaIMP-6 and blaCTX-M-2 confers a stealth-type carbapenem resistance phenotype on members of the family Enterobacteriaceae that 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.

A novel metallo-β-lactamase, IMP-34, in Klebsiella isolates with decreased resistance to imipenem

We investigated 5 metallo-β-lactamase (MBL)-positive Klebsiella isolates from Japan showing intermediate resistance to imipenem. Sequencing of the MBL gene identified a novel variant of IMP-1 with a single amino acid substitution, Glu87Gly. This variant is designated as IMP-34 where blaIMP-34 is located on a transmissible plasmid.

Imipenem-Susceptible, Meropenem-Resistant Klebsiella pneumoniae Producing OXA-181 in Japan

The incidence of infections by Enterobacteriaceae carrying the carbapenemase gene showing a paradoxical phenotype of resistance to virtually all s-lactams, including meropenem but not including imipenem, is increasing ([1][1], [2][2], [3][3]). Here we report the first isolation of Klebsiella

Meropenem Resistance in Imipenem-Susceptible Meropenem-Resistant Klebsiella pneumoniae Isolates Not Detected by Rapid Automated Testing Systems

ABSTRACT Klebsiella pneumoniae showing high resistance to all β-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.

Pharmacokinetics and pharmacodynamic target attainment of intravenous pazufloxacin in the bile of patients undergoing biliary pancreatic surgery

Abstract The study aimed to characterize the pharmacokinetics and pharmacodynamics of pazufloxacin (PZFX) in bile and to identify optimal dosing regimens. Pazufloxacin 500 mg was administered via a 0·5-hour intravenous infusion to 10 patients with endoscopic nasal bile drainage before or after biliary pancreatic surgery. Both blood and bile samples were collected pre-dose and at the end of infusion (0·5 hours) and for up to 5 hours thereafter. Concentrations of PZFX were determined using high-performance liquid chromatography. Noncompartmental and compartmental pharmacokinetic parameters were estimated, and Monte Carlo simulation was conducted to evaluate the pharmacodynamic exposure of PZFX in bile. The bile/plasma ratios were 3·58±1·15 in the area under the drug concentration–time curve (AUC) and 2·13±0·74 in the maximum drug concentration (Cmax). The delay in the time to Cmax, from plasma to bile, was 0·75±0·18 hours The probability of attaining pharmacodynamic targets (both AUC/MIC = 100 and Cmax/MIC = 8) in bile against a minimum inhibitory concentration (MIC) of 2 mg/l was >90% when PZFX was administered by a 0·5-hour infusion with 500 mg every 8 hours or 1000 mg every 12 hours These regimens provided an adequate antibacterial effect against the most common pathogens of biliary tract infections, Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae with their MICs<2 mg/l.

Tripoli metallo-β-lactamase-1 (TMB-1)-producing Acinetobacter spp. with decreased resistance to imipenem in Japan

We recently reported Klebsiella pneumoniae carrying bla IMP-type metallo-β-lactamase gene variants showing a paradoxical resistance phenotype: resistance to virtually all β-lactams except imipenem ([1][1], [2][2]). Here we report the isolation of Acinetobacter spp. showing a similar resistance

Rapid detection of blaIMP-6 by amplification refractory mutation system.

Klebsiella pneumoniae resistant to almost all ß-lactams except imipenem designated as ISMRK (imipenem-susceptible meropenem-resistant Klebsiella) is emerging in Japan. All ISMRK carries bla(IMP-6) which differs from bla(IMP-1) by only a single nucleotide at position 640. We devised a rapid detection system of bla(IMP-6) by using ARMS PCR.

Usefulness of computed tomography as a preoperative diagnostic modality in a case with acute jejunogastric intussusception.

A 72-year-old man was admitted to our hospital with an acute abdomen 1 h after the abrupt onset of hematemesis and upper abdominal pain. His medical history included a distal gastrectomy for gastric cancer 15 years previously and a subsequent gastrojejunostomy with Braun’s anastomosis because of an anastomotic stricture. Physical examination at the time of admission revealed diffuse abdominal tenderness with muscular guarding and a palpable firm mass in the left upper quadrant. A plain X-ray of the abdomen showed dilatation of the small intestine, but this finding was not specific enough to lead to a diagnosis. A subsequent abdominal computed tomography (CT) showed intestinal loops intussuscepted into the patient’s severely dilated gastric remnant through the gastrojejunostomy (Fig. 1a). Contiguous CT sections identified a normal afferent loop and intussuscepted efferent loops extending into the lower abdomen (Fig. 1b, c). Together, these findings suggested that the intussusception into the stomach involved the efferent loop, indicating the presence of a type II jejunogastric intussusception (JGI). The patient was immediately taken into surgery. Surgery revealed a severely dilated stomach stump and an 80-cm-long efferent intestinal loop that had intussuscepted in a retrograde direction at the gastrojejunostomy into the remnant gastric lumen, passing over the Braun’s anastomosis, which is in agreement with the preoperative diagnosis made by CT (Fig 2). After unsuccessful efforts to reduce this invagination by Hutchinson’s procedure,partial resection of a 100-cm-long small intestine, with end-to-end anastomosis and efferent loop fixation, was subsequently performed. The resected specimen was found to be gangrenous without perforation for a distance of 10 cm below the Braun’s anastomosis. No abnormalities such as a tumor, ulcer, diverticulum, or stenosis were identified that could have acted as a leading point for the intussusception. The JGI in this case was thus considered to be a late complication of gastrojejunostomy with Braun’s anastomosis. J Gastrointest Surg (2007) 11:1078–1080 DOI 10.1007/s11605-007-0125-z

Persistence and Epidemic Propagation of a Pseudomonas aeruginosa Sequence Type 235 Clone Harboring an IS26 Composite Transposon Carrying the blaIMP-1 Integron in Hiroshima, Japan, 2005 to 2012

ABSTRACT A 9-year surveillance for multidrug-resistant (MDR) Pseudomonas aeruginosa in the Hiroshima region showed that the number of isolates harboring the metallo-β-lactamase gene blaIMP-1 abruptly 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. aeruginosa strain harboring the blaIMP-1 gene and an aminoglycoside 6′-N-acetyltransferase gene, aac(6′)-Iae in a class I integron (In113), whose integrase gene intl1 was disrupted by an IS26 insertion. Sequence analysis of the representative strain PA058447 resistance element containing the In113-derived gene cassette array showed that the element forms an IS26 transposon embedded in the chromosome. It has a Tn21 backbone and is composed of two segments sandwiched by three IS26s. In Japan, clonal nationwide expansion of an MDR P. aeruginosa NCGM2.S1 harboring chromosomally encoded In113 with intact intl1 is 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 IS26 present in both resistance elements, we suggest that the MDR P. aeruginosa clone causing the epidemic in Hiroshima for the past 9 years originated from a common ancestor genome of PA058447 and NCGM2.S1 through an IS26 insertion into intl1 of In113 and through IS26-mediated genomic rearrangements.