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The activity of RP 59500 against Gram-positive cocci was determined by an agar dilution method and compared with that of erythromycin, cefotaxime and ampicillin. Of the 344 clinical isolates tested, none was resistant to RP 59500; this compound was active both against methicillin-resistant Staphylococcus aureus and against macrolide-resistant Gram-positive cocci. The bactericidal activity of RP 59500 was confirmed by killing curve determinations. [ABSTRACT FROM PUBLISHER]

The β-lactamase from Escherichia coli ML 4953 pKU56 was purified about 190-fold from the crude cell-free extract with an overall recovery of 17%. The molecular weight mediated by pKU56 was about 28,000, and the isoelectric point was about 9.4. This enzyme hydrolyzed cephaloridine, cephalothin, cefamandole, cefuroxime, and cefsulodin at high rate, but ampicillin, piperacillin, and carbenicillin moderately. Antisera against pKU56 enzyme showed partly cross-reaction with β-lactamase from Klebsiella oxytoca and Proteus vulgaris. [ABSTRACT FROM AUTHOR]

The article analyzes gene sequences surrounding the C protein β antigen (bac) gene, encoding Bac, of the representative group B streptococci strains from colonized women and from invasive neonatal infections. It investigates whether sequence variability exists among the strains with different Bac expression levels, and their association with factor H-binding as well as with the previously described IgA-binding abilities.

Chronic hepatitis B (CHB) leads to cirrhosis and hepatocellular carcinoma (HCC). With a cohort of 1,206 CHB patients who visited Okayama University Hospital and related hospitals in 2011 and 2012, we compared the incidence rates of HCC among the patients grouped by age, hepatitis B virus (HBV) DNA, hepatitis B e antigen (HBeAg), and treatment. HCCs were observed in 115 patients with the median observation period of 1,687 days. Among the HCC patients aged > 35 years, HBV DNA > 4 log copies/mL and positive HBeAg at diagnosis (n＝184), the HCC incidence rate was 8.4% at 5 years in the entecavir (ETV)-treated patients, 21.8% in the lamivudine (LVD)-treated patients, and 26.4% among the patients not treated with drugs. The cumulative HCC incidence was significantly reduced in the ETV-treated patients compared to those treated with LVD or not treated (p＝0.013). Among the patients aged >35 years with HBV DNA > 4 log copies/mL and negative HBeAg (n＝237), the cumulative HCC incidence was 14.6% in 5 years in ETV group and 13.9% among those not treated with a drug (p＞0.05). Only small numbers of HCCs occurred in other patients. In CHB patients aged > 35 years with HBV DNA > 4 log copies/mL and positive HBeAg, ETV treatment is recommended for the suppression of HCC development.

We report a 67-year-old woman who had stiff shoulders and anemia. Upper gastrointestinal endoscopy revealed a pedunclated nodular submucosal tumor with erosions and surface ulcers in the second portion of the duodenum. These endoscopic findings were thought to be characteristic of gangliocytic paraganglioma. CT scan revealed suspected lymph node metastasis, thus the tumor was resected with pancreaticoduodenectomy and was found to be a gangliocytic paraganglioma associated with lymph nodal metastasis. Due to the rarity of the disease there is no consensus regarding treatment. Although this tumor is considered benign, the possibility exists for regional lymph nodal spread. The treatment should be well planned with continuous careful evaluation.

A 79-year-old man was admitted with hematemesis. Emergency upper gastrointestinal tract endoscopy revealed bleeding from the papilla of Vater. Computed tomography showed cholecystitis with a gallstone and a hematoma in the gallbladder. Angiography demonstrated a pseudoaneurysm of the anterior branch of the right hepatic artery. Emergency selective transcatheter arterial embolization (TAE) was performed, with intravascular microcoils, and complete occlusion of the pseudoaneurysm was achieved. This case shows embolization is effective in the treatment of pseudoaneurysm rupturing in the gallbladder.

An 85-year-old man with HCV infection and diabetes mellitus was diagnosed as having hepatocellular carcinoma (HCC, 13 cm in diameter) based on high serum alpha-fetoprotein (AFP), AFP-L3, and des-gamma-carboxy prothrombin levels as well as typical enhancement pattern on contrast-enhanced CT. The patient did not receive any interventional treatments because of advanced age and the advanced stage of HCC. He chose to take vitamin K, which was reported to suppress the growth of HCC in vitro. Three months after starting vitamin K, all three tumor markers were normalized and HCC was markedly regressed, showing no enhancement in the early arterial phase on CT. Here we present the report describing the regression of HCC during the administration of vitamin K.

AmpC regulatory genes in 21 ceftazidime-resistant clinical isolates of Enterobacter cloacae (MICs of > or = 16 microg/ml) were characterized. All isolates exhibited AmpC overproduction due to AmpD mutation. Additionally, we found two AmpR mutants among the isolates. This is the first report of chromosomal ampR mutation in clinical isolates of E. cloacae.

A clinical isolate of Escherichia coli from a patient in Japan, isolate KU6400, was found to produce a plasmid-encoded beta-lactamase that conferred resistance to extended-spectrum cephalosporins and cephamycins. Resistance arising from production of a beta-lactamase could be transferred by either conjugation or transformation with plasmid pKU601 into E. coli ML4947. The substrate and inhibition profiles of this enzyme resembled those of the AmpC beta-lactamase. The resistance gene of pKU601, which was cloned and expressed in E. coli, proved to contain an open reading frame showing 99.8% DNA sequence identity with the ampC gene of Citrobacter freundii GC3. DNA sequence analysis also identified a gene upstream of ampC whose sequence was 99.0% identical to the ampR gene from C. freundii GC3. In addition, a fumarate operon (frdABCD) and an outer membrane lipoprotein (blc) surrounding the ampR-ampC genes in C. freundii were identified, and insertion sequence (IS26) elements were observed on both sides of the sequences identified (forming an IS26 composite transposon); these results confirm the evidence of the translocation of a beta-lactamase-associated gene region from the chromosome to a plasmid. Finally, we describe a novel plasmid-encoded AmpC beta-lactamase, CFE-1, with an ampR gene derived from C. freundii.

A Klebsiella pneumoniae strain was isolated from a sputum specimen of a patient in the intensive care unit in 1999 in Shanghai Huashan Hospital, China. The isolate was confirmed as an extended-spectrum beta-lactamase (ESBL) producing strain by double-disk synergy test. The results of susceptibility test showed that it was resistant to most beta-lactams (including third generation cephalosporins) and non-beta-lactam antimicrobial agents. Transconjugants were obtained at a frequency of 10(-4). A plasmid of about 60 kb was obtained from the transconjugant by plasmid extraction. Three major nitrocefin-hydrolysing bands with pIs of 5.4, 8.2 and 8.4, were shown in extracts of the transconjugant. Partial gene amplification products of bla(TEM), bla(SHV), and CTX-M-1 group gene were obtained from the isolate as well as its transconjugant. The entire bla(TEM), bla(SHV), and bla(CTX-M) in the transconjugant were amplified by PCR and the PCR products were cloned into a pHSG398 vector. Afterwards, the susceptibility of transformants and activities of beta-lactamases of transformants on antibiotics were tested. The PCR products were directly sequenced, analysed and identified as TEM-1, SHV-12, and CTX-M-3 genes. These results confirm that this strain of Klebsiella pneumoniae produces SHV-12, CTX-M-3 ESBLs and TEM-1 beta-lactamase, encoded by one single plasmid, which is responsible for the resistance of this strain to most beta-lactams.

Extended-spectrum beta-lactamases (ESBLs) are an increasing cause of resistance to third-generation cephalosporins in Enterobacteriaceae. However, they have not been well studied in China. We investigated the prevalence, resistance, and probable gene type of ESBLs using MICs testing and polymerase chain reaction in 559 Klebsiellae pneumoniae and 427 Escherichia coli isolates collected from patients in Huashan Hospital from 1 January to 31 December 1999. The incidence of ESBL-producing strains was 51% among Klebsiellae pneumoniae (285/559) and 23.6% among Escherichia coli (101/427), most of which were collected from patients in intensive care unit and neurosurgical ward. PFGE showed that some epidemic ESBL-producing strains were present in the ICU, especially among ESBL-producing Klebsiellae pneumoniae. The major source of ESBL-producing Klebsiellae pneumoniae and Escherichia coli was sputum specimen (63.5%) and urine (64.3%), respectively. These strains were resistant to most beta-lactams (including the third-generation cephalosporins and monobactams) and non-beta-lactams (such as fluoroquinolones, aminoglycosides, tetracycline, and chloramphenicol), all or most ESBL producers were susceptible to imipenem, cefmetazole and beta-lactam/clavulanic acid. TEM was the main type of beta-lactamases and the CTX-M type of ESBLs was common in these isolates. Some ESBL-producing Escherichia coli and most ESBL-producing Klebsiellae pneumoniae produced more than one type of beta-lactamase. These data confirm that ESBL producers are common among hospital strains of Escherichia coli and Klebsiellae pneumoniae in China. It is important to monitor such strains closely and prevent their spread.

Emergence of bacterial resistance has rendered ineffective a number of previously valuable antibiotic treatments and now threatens the effectiveness of others. beta-Lactam resistance is no longer predominantly a hospital-treated problem; it has now become an important issue in community medicine. More than 100-beta-lactamases have been identified and classified according to their structure, substrate specificity, and whether they are chromosomal or plasmid-mediated. beta-Lactamase production is rare among Gram-positive pathogens, important exceptions being Staphylococcus aureus and Enterococcus faecalis. By contrast, many Gram-negative pathogens are beta-lactamase-positive; inducible and/or hyper-productive strains are particularly challenging in the clinical setting. Surveillance programs have shown that, in general, beta-lactam resistance is on the increase, and that the plasmid-mediated beta-lactamase have developed rapidly over past decade such as ESBLs and carbapenemases.

We encountered three clinical isolates of methicillin-resistant Staphylococcus aureus which were susceptible to netilmicin and arbekacin in the absence of beta-lactam antibiotics but which were resistant to them in the presence of beta-lactam antibiotics. One of these strains, KU5801, was used to further investigate the antagonism between aminoglycosides and beta-lactam antibiotics. beta-Lactam antibiotics induced bacterial synthesis of aminoglycoside-6'-N-acetyltransferase and 2"-O-phosphotransferase [AAC(6')-APH(2")] in association with decreased antimicrobial activities of aminoglycosides. A 14.4-kb EcoRI fragment that included the genes that control for beta-lactam-inducible aminoglycoside resistance was cloned from a 31-kb conjugative plasmid present in KU5801. Restriction fragment mapping and PCR analysis suggested that a Tn4001-like element containing a gene encoding AAC(6')-APH(2") was located downstream from a truncated blaZ gene. The DNA sequence between blaR1 and a Tn4001-like element was determined. The Tn4001-IS257 hybrid structure was cointegrated into the blaZ gene, and the typical sequences for the termination of transcription were not found between these regions. We deduced that antagonism of aminoglycosides by beta-lactam antibiotics in isolate KU5801 involved transcription of the aac(6')-Ie-aph(2")-Ia gene under the influence of the system regulating penicillinase production.