Nephrotoxicity induced by piperacillin­tazobactam in late elderly Japanese patients with nursing and healthcare associated pneumonia.

This study aimed to clarify the efficacy, safety, and pharmacokinetics of piperacillin­tazobactam (PIPC­ TAZ) in late elderly Japanese patients. This is the first antimicrobial pilot study in late elderly patients with nursing and healthcare associated pneumonia. After PIPC­TAZ administration, PIPC concentrations in plasma were measured chromatographically and the pharmacokinetic parameters were estimated. Efficacy, safety, and bacteriological evaluations were also carried out. The mean age was 85.0 years old and most of the patients were late elderly. Chest X-rays, body temperature, white blood cell count, and C reactive protein all improved significantly, and a high efficacy ratio of 90.9% was observed. Serious nephrotoxicity was observed in 4 cases (18.2%) after administration of PIPC­TAZ. Creatinine clearance (meanS.D.) measured before PIPC­TAZ therapy was significantly lower in the nephrotoxicity group (32.54.4 mL/min) than in the non-nephrotoxicity group (46.116.7 mL/min), although the ages were not different between the 2 groups. In the pharmacokinetic parameters for PIPC, total clearance was slightly lower in the nephrotoxicity group than in the non-nephrotoxicity group. However, no significant difference was observed in plasma PIPC levels between the 2 groups. In patients with renal impairment, especially with a creatinine clearance of <40 mL/ min, renal impairment was found to be an influencing factor for severe nephrotoxicity following PIPC­TAZ administration. In conclusion, the results suggest that physicians should pay close attention in order to avoid possible toxicity, and that deliberate administration planning and careful follow-up are required in late elderly patients with comprised organ dysfunction.

[Usefulness of the Loopamp Mycoplasma P Detecting Reagent Kit developed based on the LAMP method].

Pathogenic bacteria of Mycoplasma pneumonia, Mycoplasma pneumoniae, do not respond to ß-lactam antimicrobial agents. Therefore, it is clinically important to promptly identify infection with this type of bacteria. However, conventional examination methods such as culture and antibody tests are not useful for the rapid diagnosis of this bacterial type. In this study, we examined a Loopamp Mycoplasma P-detecting Reagent Kit developed based on the LAMP (Loop-mediated isothermal amplification) method, which may overcome the limitations of the conventional methods. The consistency rate for the conventional polymerase chain reaction (PCR) method was 98.3%. That for a rapid antibody test, immunocard Mycoplasma antibody, was 54.0%, suggesting the limitation of the rapid antibody test. We compared a pretreatment method using a Loopamp PURE DNA Extraction Kit, as a simple DNA extraction method, with that using a QIAamp DNA Mini Kit. The consistency rate was 91.4%, suggesting the usefulness of the simple DNA extraction method. The use of this kit may facilitate a more rapid diagnosis. The Loopamp Mycoplasma P-detecting Reagent Kit is useful for the accurate and rapid diagnosis of Mycoplasma pneumoniae infection.

Evaluation of the efficacy and safety of biapenem against pneumonia in the elderly and a study on its pharmacokinetics.

Although biapenem is used in the treatment of pneumonia, the clinical data on elderly patients are yet insufficient. Therefore, the purpose of this study was evaluating the efficacy and safety of biapenem against pneumonia in the elderly and its pharmacokinetics. The subjects were patients 65 years of age or older with pneumonia. Biapenem (300 mg) was administered once to three times per day. For some cases, the drug concentrations in plasma were measured chronologically. The clinical efficacy was evaluated in reference to the improvement in subjective symptoms and objective opinion. The primary outcome was efficacy rate at the end of treatment. Biapenem was effective in 17 of 20 subject cases (85.0 %). Regarding safety, although 4 cases experienced hepatic dysfunction and 1 case had nausea, these effects were not severe in all cases and administration was continued. There was no deterioration of renal function associated with biapenem. In 13 cases in which the trough value of biapenem was measured, there were no unacceptable side effects and the trough values were generally low. It is believed that biapenem (300 mg once to three times a day), even when taken by elderly people, does not accumulate and that the dosage is safe and appropriate. The changes in the predicted concentrations calculated with the pharmacokinetic-pharmacodynamic (PK-PD) software, which is based on previously reported population pharmacokinetic parameters, and those in the measured concentrations approximately matched. It is useful to plan biapenem administration using the PK-PD software when performing antibiotic chemical treatment.

[Usefulness of phage ORF typing, a rapid genotyping method as a molecular and epidemiological method for detecting methicillin resistant Staphylococcus aureus].

Surveillance is very important for preventing the nosocomial spread of methicillin-resistant Staphylococcus aureus (MRSA), and the pulsed-field gel electrophoresis (PFGE) method has long been used to identify the infection source and route as a molecular and epidemiological genotyping method. However, the use of the method in routine clinical laboratory measurements is difficult due to its complicated procedures. Since a molecular and epidemiological genotyping kit based on the POT (Phage Open-reading Frames Typing) method has been developed, we examined 192 MRSA isolates newly detected from inpatients in our hospital in 2010 in order to investigate the usefulness of POT for surveying outbreaks of MRSA. Among the 192 isolates 118 were suspected of nosocomial spread by the previous method, which defined a MRSA detection at more than 48 hours after admission as a nosocomial spread. The POT method was introduced at our laboratory in 2010, and we were able to recognize 38 patients as having strongly suspected nosocomial MRSA infection with the POT method taking into consideration the infection situation, such as places (wards and transfer) and time (date of admission and date of collected samples). Our Infection Control Division was confidently able to demonstrate the current condition of the nosocomial spread by providing the results to the clinical staff, who were also able to practice infection control confidently. We concluded that the POT method was very useful and convenient for investigating MRSA isolates and evaluating collected data because no particular analysis other than the digitizing electrophoretic pattern method was necessary.

Limited detectability of linezolid-resistant Staphylococcus aureus by the Etest method and its improvement using enriched media.

The aim of this study was to evaluate Etest for detectability of linezolid-resistant meticillin-resistant Staphylococcus aureus (MRSA). The MIC of linezolid obtained by the Etest method in 18 linezolid-resistant strains of MRSA was compared with that obtained using standard agar and broth dilution methods according to Clinical and Laboratory Standards Institute guidelines. The mean linezolid MIC obtained by Etest in 18 linezolid-resistant strains of MRSA using Mueller-Hinton (MH) agar was 12.6-fold lower than that obtained by the agar dilution method, with the result that 78 % of the linezolid-resistant strains were incorrectly classified as linezolid-susceptible. The MIC of linezolid by Etest on brain-heart infusion (BHI) agar had a mean value 2.5-fold lower than that obtained by the agar dilution method, suggesting that replacing MH agar with BHI agar considerably improved the detectability of linezolid-resistant MRSA. Use of blood agar (MH agar supplemented with 5 % sheep blood) and 48 h of incubation resulted in 100 % agreement with the agar and broth dilution methods. Thus, this study revealed that the Etest on MH agar and BHI agar yielded false-negative results in a significant fraction of the linezolid-resistant MRSA. Hence, the use of blood agar and prolonged incubation is highly recommended for the accurate detection of linezolid-resistant MRSA using Etest.

[One example of false negative hepatitis B surface antigen (EIA) result due to variant S area strain and reagment reactiveness related to hepatitis B surface antigen].

The presence in serum of the Hepatitis B surface antigen (HBsAg), the outer envelope of the hepatitis B virus (HBV), indicates viral infection, used in laboratory tests to confirm this. We report a case of discrepancy among HBsAg test results detected between measurements in a subject with HB infection. Gene analysis demonstrated several S region gene mutations, not detected previously. We tested 12 measurements e.g., EIA, CLIA, CLEIA, F-EIA, MAT, and IC for whether they could detect our subject's HBsAg and found that it was not recognized by a method using only a single monoclonal antibody to detect HBsAg in two detection processes, in contrast to the 11 other measurements, which used two different antibodies. This case shows that amino acid substitution may cause a false negative result for HBsAg. Gene mutations known to occur in HBV, should thus trigger an awareness of the need to keep in mind that false negative results can happen in case such as ours.

Septic shock induced by Lecythophora mutabilis in a patient with mitochondrial encephalomyopathy.

Invasive fungal infection (IFI) caused by Lecythophora mutabilis occasionally occurs in patients with impaired host immunity; such patients had eosinophilia at onset, and surviving patients were treated with fungal cell-membrane-targeted drugs. An 18-year-old man with mitochondrial encephalomyopathy accompanied with refractory anaemia and chronic renal failure developed septic shock caused by L. mutabilis, which was detected from a blood culture, and was identified morphologically and genetically. During the course of the infection, he had eosinophilia, although beta-d-glucan levels were within the normal range. He was treated with micafungin, but deteriorated and died, despite his treatment being changed to liposomal amphotericin B. On the basis of this we suggest that IFI caused by L. mutabilis should be suspected when a compromised host develops infection and eosinophilia, and that antifungal drugs that target beta-d-glucan are not advisable.

Correlation of NO metabolites and 8-iso-prostaglandin F2a with periventricular hyperintensity severity.

OBJECTIVE: Oxidative stress and NO are thought to play important roles in arteriosclerosis pathogenesis, a major cause of white matter lesions in the brain. Therefore, we examined whether NO metabolites (NOx) and 8-iso-prostaglandin F(2alpha) (IsoP) levels in vivo correlated with the severity of periventricular hyperintensity (PVH) to evaluate potential roles of oxidative stress and NO in white matter lesions. METHODS AND RESULTS: Participants (687 males and 528 females) of a health-screening examination were recruited into the study. The plasma NOx and urinary IsoP levels were measured using the Griess method and ELISA, respectively. PVH was diagnosed on the basis of MRIs. In nonparametric univariate trend analyses, plasma NOx as well as aging, presence of hypertension and of lacunes, mean blood pressure, and high-density lipoprotein cholesterol showed highly significant monotone correlation with PVH severity (P

T-786C polymorphism in endothelial NO synthase gene affects cerebral circulation in smokers: possible gene-environmental interaction.

Effects of smoking on white matter lesions, such as lacunar infarction and leukoaraiosis, are still controversial. We hypothesized that the endothelial NO synthase (eNOS) genotype was a modulating factor for the effect of smoking on cerebral circulation. We took a cross-sectional population from the participants of a health examination to study the effects of smoking and a single-nucleotide polymorphism in the eNOS gene, T-786C. Smokers and nonsmokers were defined as having a smoking index (cigarettes per day times years) of >/=200 and 0, respectively. One hundred sixty-six male nonsmokers and 344 male smokers were recruited. Cerebral blood flow was measured by the (133)Xe inhalation method. Genotyping of T-786C was performed by using a newly developed allele-specific polymerase chain reaction. Smokers were exposed to greater oxidative stress, as estimated by urinary F(2)-isoprostane excretion. In smokers, CC homozygotes of T-786C showed a significant decrease of cerebral blood flow (56.6+/-13.3, 57.6+/-11.5, and 44.0+/-7.2 mL/min per 100 g tissue for TT, TC, and CC, respectively; P=0.03 by ANOVA) and a significant increase of cerebrovascular resistance, whereas the eNOS genotype did not affect these parameters in nonsmokers. This result indicated that the eNOS genotype could modify cerebrovascular circulation in a general population by potentiating the adverse effect of smoking.