Validation of a commercial serodiagnostic kit for diagnosing pulmonary Mycobacterium avium complex disease.

SETTING: A commercial serodiagnostic kit for diagnosing pulmonary disease due to Mycobacterium avium complex (MAC-PD) was developed and launched in Japan in 2011. OBJECTIVE: To evaluate the performance of this kit in routine clinical settings. METHODS: In this retrospective single-centre study, data on serum levels of anti-glycopeptidolipid (GPL) core IgA antibody (U/ml) measured using the kit were analysed in patients diagnosed with MAC-PD according to American Thoracic Society criteria, in those with pulmonary tuberculosis (PTB) or pulmonary M. kansasii disease and in healthy volunteers. RESULTS: The anti-GPL-core IgA antibody levels of serum were significantly higher (P < 0.0001) in patients with MAC-PD (n = 485) than in those with PTB (n = 133) or pulmonary M. kansasii disease (n = 23) or in healthy subjects (n = 265). When the cut-off level was set at 0.7 U/ml, the sensitivity and specificity were respectively 78.6% and 96.9%. Higher antibody levels were observed in patients with greater extent of disease on chest computed tomography (P < 0.0001). CONCLUSIONS: The serodiagnostic kit revealed good sensitivity and specificity. The antibody levels may reflect disease activity. Additional work is needed to determine whether the diagnostic assay could be used in conjunction with current diagnostic criteria to improve the diagnosis of MAC-PD.

Long-term radiographic outcome of nodular bronchiectatic Mycobacterium avium complex pulmonary disease.

BACKGROUND: Although Mycobacterium avium complex pulmonary disease (MAC-PD) is a growing health problem, little is known about long-term radiographic outcome and factors for deterioration in patients with MAC-PD. METHODS: Data on patients with nodular bronchiectatic (NBE) MAC-PD who underwent regular follow-up for >5 years were retrospectively reviewed. Changes in plain chest radiograph (CXR) and baseline characteristics were compared between the stable and deteriorated groups. RESULTS: Seventy-two patients were investigated, including 30 patients who were examined 10 years after the initial visit. One patient (1.4%) showed progressive or remarkably progressive disease on CXR at 1 year; this rate increased to 22.2% at 5 years and to 53.3% at 10 years. Body mass index (BMI) at the initial visit was lower in the deteriorated group than in the stable group. Cavitary disease and resistance to a macrolide were seen more frequently at the initial visit in the deteriorated group than in the stable group. CONCLUSIONS: NBE MAC-PD is a slowly but substantially progressive long-term infection (5-10 years). Our data suggest that patients with lower BMI, cavitary disease and resistance to a macrolide at initial visit are more likely to progress to deteriorating disease.

[Effects of an oxacephem antibiotic on liver function in orthopedic surgery].

The subjects were 531 patients who underwent orthopedic surgery. Flomoxef was administered, and liver function was examined before and after administration. Abnormal liver function after administration of flomoxef was found in 14.3% of patients. In male patients, a high rate of 18.8% was observed. A particularly high rate of 37.0% was obtained among patients who showed GOT values of more than 40 U/L before treatment with flomoxef. The prevalence of abnormal GOT and GPT values after administration of flomoxef was 3.6% and 13.2%, respectively. These values were significantly higher than those obtained with other cephem antibiotics. These rates of occurrence of abnormally high GOT and GPT are obviously higher than those submitted at the time of approval and reported in the drug use investigation. The prevalence of abnormal liver function values was high in patients receiving flomoxef, and particularly high in male patients and patients whose GOT was high before administration of flomoxef. Therefore, sufficient check of liver function appears important when administration of flomoxef to these types of patients is intended.

[A consideration on the results of nationwide surveillance of antimicrobial susceptibilities--gram-negative bacilli].

The results of the semi-annual nationwide surveillance of antimicrobial susceptibilities, conducted by the Japanese Ministry of Health and Welfare during the period of January 1993 to July 1995, were analyzed for typical Gram-negative bacilli in the purpose of provision of an index for antimicrobial selection. During these 3 years, Escherichia coli, Citrobacter freundii, Enterobacter aerogenes and Proteus mirabilis showed slightly increasing tendency in susceptibility to fosfomycin (FOM) and Citrobacter freundii. Klebsiella pneumoniae and Enterobacter aerogenes showed slightly increasing tendency to minocycline (MINO). While Haemophilus influenzae and Haemophilus parainfluenzae showed slightly decreasing tendency to cefmetazole (CMZ). However, these annual changes were almost negligible. Generally, these microorganisms showed relatively good susceptibilities, every year, to the principal antimicrobial agents being approved for use against Gram-negative bacilli. However, Enterobacter cloacae, Enterobacter aerogenes, Serratia marcescens and Pseudomonas aeruginosa showed tendencies of decreased susceptibility to some of the antimicrobial agents. On the other hand, sulfamethoxazole-trimethoprim (ST), CMZ, latamoxef (LMOX), gentamicin (GM) and amikacin (AMK) showed good activities against some of the Gram-negative bacilli to which no indications are approved. In conclusion, bedside the identification of the causative microorganisms and the performance of antimicrobial susceptibility testing, such analyses (graphics of susceptibility tendency of clinical isolates to variety of antimicrobial agents) could be used as an index for selection of antimicrobial agents, when emergent and urgent selection of antimicrobial agents is necessary.

[A consideration on the results of nationwide surveillance of antimicrobial susceptibilities--gram-positive cocci and gram-negative cocci].

The results of the semi-annual nationwide surveillance of antimicrobial susceptibilities, conducted by the Japanese Ministry of Health and Welfare during the period of January 1993 to July 1995, were analyzed for typical Gram-positive cocci and Gram-negative cocci in the purpose of provision of an index for antimicrobial selection. During these 3 years, Streptococcus pyogenes (group A) and Streptococcus agalactiae (group B) showed slightly increasing tendency in susceptibility to ofloxacin (OFLX) and sulfamethoxazole/trimethoprim (ST), while Streptococcus pneumoniae and Moraxella (Branhamella) catarrhalis showed slightly decreasing tendency to cefaclor (CCL). However, these annual changes were almost negligible. Generally, these microorganisms showed relatively good susceptibilities, every year, to the principal antimicrobial agents being approved for use against Gram-positive and -negative cocci. However, Staphylococcus aureus, Staphylococcus epidermidis and Enterococcus faecalis showed tendencies of decreased susceptibility to some of the antimicrobial agents. On the other hand, cefmetazole (CMZ), vancomycin (VCM), latamoxef (LMOX), ST and minocycline (MINO) showed good activities against some of the Gram-positive and -negative cocci to which no indication are approved. In conclusion, beside the identification of the causative microorganisms and the performance of antimicrobial susceptibility testing, such analyses (graphics of susceptibility tendency of clinical isolates to variety of antimicrobial agents) could be used as an index for selection of antimicrobial agents, when emergent and urgent selection of an antimicrobial agent is necessary.

[Protein binding of clarithromycin in patients with chronic renal failure].

Assessment was made on the serum protein binding of clarithromycin (CAM), a representative oral macrolide, using sera from healthy subjects (HS) and patients with chronic renal failure (CRF) applying equilibrium dialysis in vitro. The protein binding of CAM was 81.9 +/- 1.9%, 85.9 +/- 3.6%, 82.9 +/- 3.3% and 86.8 +/- 3.3% for sera from HS, from patients in conservative treatment (ND), from those receiving hemodialysis (HD) and from those with continuous ambulatory peritoneal dialysis (CAPD), respectively. There was no significant difference among these values. The protein binding of CAM was 82.9 +/- 3.3% and 68.8 +/- 3.5% for sera before and after HD, respectively. There was significant difference between these values. In the study of the protein binding in patients on HD at an albumin concentration of 0.5 mM, the protein binding of CAM for sera was found to be significantly decreased following HD as compared to that prior to HD. The addition of palmitic acid (PA), a common NEFA, to pooled sera from HS, the protein binding of CAM showed no change. These findings suggest that changes in the protein binding of CAM with HD have been possibly caused by an increase in a drug binding inhibiter other than NEFA (PA) or by an allosteric effect on the albumin binding capacity. At therapy using CAM, the possibility of enhanced pharmacological effects and increased adverse reactions of CAM due to decreased protein binding in patients on HD should be considered.

[Study of the usefulness of a kit containing imipenem/cilastatin powder with diluent for injection: convenience of use and preparation].

The usefulness of a newly developed imipenem/cilastatin powder-and-diluent kit packed in non-glass container was compared to that packed in commercially available glass vials. The imipenem/cilastatin powder-and-diluent kit container is made of a polyolefin bag with two chambers that contain imipenem/cilastatin powder and diluent (0.9% saline, 100 ml), respectively. The convenience of use of the kit and the time required for the preparation of the dosing solution were evaluated by nurses and pharmacists at the Kitasato University East Hospital. The newly developed kit received higher scores with regard to convenience of use and led to a 46 approximately 59% reduction in the time required for preparation as compared to the commercially available glass vials.

[Study of the usefulness of a kit containing imipenem/cilastatin powder with diluent for injection: accuracy of reconstitution].

The usefulness of a kit consisting of non-glass packaging was evaluated in terms of accuracy of reconstitution. The newly developed imipenem/cilastatin powder-and-diluent kit consists of a polyolefin bag with two chambers that contain impenem/cilastatin powder and diluent (0.9% saline, 100 ml), respectively. The accuracy of reconstitution was determined by nurse and pharmacists at the Kitasato University East Hospital by measuring the amount of materials remaining in vials after reconstitution using the syringe dilution method and the transfer-needle dilution method. The mean percent amounts of imipenem and cilastatin remaining after preparation by the syringe dilution method were 5.58 +/- 2.60% and 4.08 +/- 1.77%, respectively. The mean percent amounts of imipenem and cilastatin remaining after preparation by the transfer-needle dilution method were 3.99 +/- 2.28% and 3.71 +/- 2.09%, respectively. The amount of imipenem/cilastatin remaining in the newly developed kit should be negligible, because the kit serves as both a vial and a dosing package. Therefore, greater accuracy in terms of reconstitution is expected with the newly developed kit than with the traditional syringe dilution or transfer-needle dilution methods.

[Protein binding of oral cephems in patients with chronic renal failure].

An assessment was made of the serum protein binding of representative oral cephems (cefdinir, cefixime and ceftibuten) for sera from healthy subjects (HS) and patients with chronic renal failure (CRF) using an application of equilibrium dialysis under a same set of conditions in vitro. The protein binding capacity of oral cephems in CRF patients being treated with continuous ambulatory peritoneal dialysis (CAPD) or hemodialysis (HD) was significantly less than that in HS, and a marked increase in free drug concentration was observed. While examining the protein binding of oral cephems with heparin in patients on HD, binding capacity decreased significantly immediately following the completion of dialysis compared to that prior to dialysis. On the other hand, the protein binding of oral cephems did not change when used nafamostat mesilate as an anticoagulant. The addition of palmitic acid (PA), a common non-esterified fatty acid (NEFA), to pooled sera from HS caused the binding capacity of oral cephems to decrease, accompanied by increase in PA concentration. It appears from these findings that changes in the binding capacity of oral cephems with HD have possibly been caused by increase in NEFA due to activation of lipase when heparin was used as an anticoagulant. In conclusion, changes in the protein binding capacity of oral cephems in CRF patients should be taken into consideration in attempts to avoid possible side effects.

[Protein binding of cephems in the elderly].

The serum protein-binding of 12 representative cephems (CET, CEZ, CZX, CPZ, CZON, CPM, CDZM, CFX, CMZ, CTT, LMOX, FMOX) was assessed, using sera from young healthy subjects (mean age, 28.6 years old) and elderly healthy subjects (mean age, 69.7 years old), applying equilibrium dialysis under the same conditions in vitro. The protein-binding capacity of 12 cephems in elderly subjects was significantly less than that in young subjects, and marked increase in free drug concentration was observed in elderly subjects. This decrease in the protein binding capacity of cephems in elderly subjects was possibly caused by decreased serum albumin and change in non-esterified fatty acid constitution related to aging. As free-drug concentration participates in the appearance of effects and adverse reactions, the possibility of an enhanced pharmacological effects and increased adverse reactions of cephems due to decrease of protein binding in elderly subjects should be considered.

[Protein binding of various cephems in healthy subjects and patients with chronic renal failure].

This study was employed to investigate whether the serum protein binding of various cephems [cefpiramide (CPM), cefalotin (CET), latamoxef (LMOX)] differ among healthy subjects and patients with chronic renal failure (CRF) by means of in vitro equilibrium dialysis. The protein binding capacities of cephems in patients with CRF (hemodialysis, continuous ambulatory peritoneal dialysis, non-dialysis) decreased significantly compared to those in healthy subjects. The binding capacities correlated directly with total protein, albumin concentration and correlated inversely with blood urea nitrogen and serum creatinine concentration. In the study of protein binding during and after hemodialysis, the binding capacities of CPM and LMOX decreased immediately after dialysis and then increased with the time. However, the binding capacities of CET increased immediately after dialysis and then decreased. The binding capacities of CPM and LMOX correlated inversely with non-esterified fatty acids (NEFA) and those of CET correlated directly with NEFA. In the study of protein binding in pooled sera from healthy subjects with or without palmitic acid (PA), the binding capacities of CPM and LMOX decreased by increasing the concentration of PA, while those of CET increased by increasing PA up to 3 mM. The changes in binding capacity of cephems during and after hemodialysis have been possibly caused by increase of NEFA due to activation of lipase in use of heparin as an anticoagulant. In conclusion, changes in protein binding capacity of cephems in sera from CRF, which should be taken into consideration to avoid possible side effects.