History of pain around the lumbopelvic region during perinatal period: a prospective cohort study.

PURPOSE: Many women experience pain around the low back and pelvic girdle during/after pregnancy. These pains have different risk factors and require independent management strategies. Therefore, an epidemiological database is required to understand when each type of pain occurs, and how serious it could be. Thus, the history of pain in the lumbopelvic region throughout the perinatal period was investigated. METHODS: The information of 170 women recruited at the obstetrics and gynecology clinics in Japan was collected at 12, 24, 30, and 36 weeks of pregnancy, in the early days after childbirth, and one month after childbirth. The presence and severity of sacroiliac joint pain, pubic pain, groin pain, and low back pain were assessed using a numerical rating scale. Descriptive statistics were used to determine changes in the prevalence of pain. In addition, the change in the severity of each type of pain was observed through descriptive statistics, by including only those who had pain. RESULTS: The sacroiliac joint pain showed a twofold increase from 12 to 24 weeks, while the pubic pain suddenly increased after 24 weeks. The severity of pubic and groin pain increased sharply during pregnancy. Regarding low back pain, the change in the severity was lesser than the other pains. The sacroiliac joint pain was the highest among the four pains during pregnancy. CONCLUSION: Each type of pain had a different incidence rate and a different time of onset and aggravation. These results help women and health professionals to manage, and prevent these harmful symptoms.

Lipid nanodiscs spontaneously formed by an amphiphilic polymethacrylate derivative as an efficient nanocarrier for molecular delivery to intact cells.

There is a great demand for the technology of molecular delivery into living cells using nanocarriers to realise molecular therapies such as gene delivery and drug delivery systems. Lipid-based nanocarriers offer several advantages for molecular delivery in biological systems, such as easy preparation, high encapsulation efficiency of water-insoluble drug molecules, and excellent biocompatibility. In this paper, we first report the interaction of lipid nanodiscs spontaneously formed by the complexation of an amphiphilic polymethacrylate derivative and phospholipid with intact cells. We evaluated the internalisation of polymethacrylate-based lipid nanodiscs by intact HeLa cells and applied them to the delivery of paclitaxel (PTX), an anticancer drug. The lipid nanodisc showed excellent uptake efficiency compared to conventional liposomes at a concentration where nanodiscs do not show cytotoxicity. In addition, the nanodisc encapsulating PTX showed significantly higher anticancer activity than PTX-loaded liposomes against HeLa cells, reflecting their excellent activity in delivering payloads to intact cells. This study demonstrated the potential of a polymethacrylate-based lipid nanodisc as a novel nanocarrier for molecular delivery to intact cells.

Ultrasound Assessment of Abdominal Muscle Thickness With and Without Lumbopelvic Pain in Pregnant Women.

OBJECTIVES: Lumbopelvic pain (LPP) is a very common cause of discomfort during pregnancy, but its etiology remains unclear. The association between abdominal muscle thickness and LPP in pregnant women has not been studied extensively, despite the significant abdominal changes that occur during pregnancy. This study aimed to examine the relationship between abdominal muscle thickness and LPP in pregnant women. METHODS: In this study, 49 pregnant women in their second trimester participated. The intensity of LPP was assessed using a numerical rating scale. Ultrasound imaging was used to measure the thickness of abdominal muscles, including the rectus abdominis, external oblique, internal oblique, and transversus abdominis muscles. Participants were classified into two groups, the LPP group and non-LPP group, and the abdominal muscle thickness was compared between the two groups. The statistical significance level was set at P < .05. RESULTS: There were 24 and 25 participants in the LPP and non-LPP groups, respectively. Internal oblique (IO) thickness was significantly thinner in the LPP group than in the non-LPP group (5.4 ± 0.2 mm versus 6.1 ± 0.2 mm; P = .042). Multivariate logistic regression analysis showed that IO thickness was significantly associated with LPP (odds ratio, 0.516; 95% confidence interval, 0.284-0.935; P = .019). CONCLUSIONS: This study suggested that LPP in second trimester pregnancy might be related to IO thickness. Further longitudinal studies are needed to understand the role of this muscle as an LPP risk factor for pregnant women.

Correlation between Antimicrobial Resistance and the Hospital-Wide Diverse Use of Broad-Spectrum Antibiotics by the Antimicrobial Stewardship Program in Japan.

Increased antibiotic use and antibiotic homogeneity cause selective pressure. This study investigated the correlation between antibiotic diversity and antimicrobial resistance (AMR) in Gram-negative organisms. The days of therapy/100 patient-days (DOT) for four broad-spectrum antibiotic classes were evaluated for 2015-2022. The antibiotic heterogeneity index (AHI) for the equal use of four classes (25%) and the modified AHI for the equal use of three classes (30%), excluding fluoroquinolones (10%), were measured (target: 1.0). Quarterly antibiotic use markers and the resistance rates against ≥2 anti-Pseudomonas antibiotics were compared. The DOT value was 9.94, and the relative DOT were 34.8% for carbapenems, 32.1% for piperacillin/tazobactam, 24.3% for fourth generation cephalosporins/ceftazidime/aztreonam, and 8.9% for fluoroquinolones. Although no correlation was found between the total DOT and the resistance rate for any bacterium, a significant negative correlation was found between the heterogeneity indices and resistance rates for Pseudomonas aeruginosa and Klebsiella pneumoniae. The significant cutoffs that discriminate the risk of resistance were 0.756 for the AHI and 0.889 for the modified AHI for K. pneumoniae. Antibiotic diversity is more important in preventing AMR than overall antibiotic use. The ideal ratio of broad-spectrum antibiotics should be studied for diversified use to prevent AMR.

Correction of thrombocytopenia caused by linezolid with scheduled sequential tedizolid use in patients with vertebral osteomyelitis by antibiotic resistant Gram-positive organisms.

INTRODUCTION: Because of thrombocytopenia, linezolid treatment tends to be stopped before the completion of therapy for complicated infections that require prolonged antimicrobial administration. In contrast, tedizolid shows a favorable hematologic profile. The primary end-point of this study was to evaluate the efficacy of switching treatment to tedizolid in patients who developed thrombocytopenia during linezolid therapy. METHODS: This retrospective study was conducted in patients with vertebral osteomyelitis (VO) caused by antibiotic-resistant Gram-positive bacteria. Treatment failure was defined as the reappearance of infection signs within 2 weeks after stopping tedizolid and discontinuation of tedizolid because of continued thrombocytopenia or other adverse effects. RESULTS: Eight patients with native VO (n = 3) and postoperative VO (n = 5) were included in the study. The causative organisms were MRSA in all patients except one. Platelet counts decreased from 35.2 ± 11.5 × 104/mm3 to 17.8 ± 6.2 × 104/mm3 during linezolid therapy and improved without washout period in all patients after switching to tedizolid on days 5-7 (28.6 ± 4.9 × 104/mm3, p = 0.002). Tedizolid therapy was completed and treatment failure was not observed in any patient. The duration of treatment was 20.0 ± 11.2 days for linezolid and 30.3 ± 9.5 days for tedizolid (total, 50.3 ± 10.7 days). One patient died because of underlying disease, and there was no recurrence in the remaining 7 patients (median follow-up 501 days). CONCLUSIONS: Switching therapy to tedizolid improved thrombocytopenia that occurred during linezolid therapy, and it enabled the completion of therapy for VO patients.

Validation of Vancomycin Area under the Concentration-Time Curve Estimation by the Bayesian Approach Using One-Point Samples for Predicting Clinical Outcomes in Patients with Methicillin-Resistant Staphylococcus aureus Infections.

Area under the concentration-time curve (AUC)-guided vancomycin treatment is associated with decreased nephrotoxicity. It is preferable to obtain two samples to estimate the AUC. This study examined the usefulness of AUC estimation via trough concentration (Cmin)-only sampling of 260 adults infected with methicillin-resistant Staphylococcus aureus (MRSA) who received vancomycin. The exact Cmin sampling time was used for Bayesian estimation. A significantly higher early treatment response was observed in patients with a day 2 AUC ≥ 400 µg·h/mL than those with <400 µg·h/mL, and a significantly higher early nephrotoxicity rate was observed in patients with a day 2 AUC ≥ 600 µg·h/mL than those with <600 µg·h/mL. These AUC cutoff values constituted independent factors for each outcome. In sub-analysis, the discrimination ability for early clinical outcomes using these AUC cutoffs was confirmed only in patients with q12 vancomycin administration. A significant difference in early treatment response using the 400 µg·h/mL cutoff was obtained only in patients with low-risk infections. The usefulness of the vancomycin AUC target to decrease nephrotoxicity while assuring clinical efficacy was even confirmed with a single Cmin measurement. However, assessment with two samples might be required in patients with q24 administration or high/moderate-risk MRSA infections.

Enhanced loading dose of teicoplanin for three days is required to achieve a target trough concentration of 20 µg/mL in patients receiving continuous venovenous haemodiafiltration with a low flow rate.

INTRODUCTION: Because of its lower risk of renal toxicity than vancomycin, teicoplanin is the preferred treatment for methicillin-resistant Staphylococcus aureus infection in patients undergoing continuous venovenous haemodiafiltration (CVVHDF) in whom renal function is expected to recover. The dosing regimen for achieving a trough concentration (Cmin) of ≥20 µg/mL remains unclear in patients on CVVHDF using the low flow rate adopted in Japan. METHODS: The study was conducted in patients undergoing CVVHDF with a flow rate of <20 mg/kg/h who were treated with teicoplanin. We adopted three loading dose regimens for the initial 3 days: the conventional regimen, a high-dose regimen (four doses of 10 mg/kg), and an enhanced regimen (four doses of 12 mg/kg). The initial Cmin was obtained at 72 h after the first dose. RESULTS: Overall, 60 patients were eligible for study inclusion. The proportion of patients achieving the Cmin target was significantly higher for the enhanced regimen than for the high-dose regimen (52.9% versus 8.3%, p = 0.003). In multivariate analysis, the enhanced regimen (odds ratio [OR] = 39.93, 95% confidence interval [CI] = 5.03-317.17) and hypoalbuminaemia (OR = 0.04, 95% CI = 0.01-0.44) were independent predictors of the achievement of Cmin ≥ 20 µg/mL. CONCLUSIONS: An enhanced teicoplanin regimen was proposed to treat complicated or invasive infections by methicillin-resistant Staphylococcus aureus in patients receiving CVVHDF even with a low flow rate.

Clinical efficacy and safety in patients treated with teicoplanin with a target trough concentration of 20 µg/mL using a regimen of 12 mg/kg for five doses within the initial 3 days.

BACKGROUND: A trough concentration (Cmin) ≥20 µg/mL of teicoplanin is recommended for the treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections. However, sufficient clinical evidence to support the efficacy of this target Cmin has not been obtained. Even though the recommended high Cmin of teicoplanin was associated with better clinical outcome, reaching the target concentration is challenging. METHODS: Pharmacokinetics and adverse events were evaluated in all eligible patients. For clinical efficacy, patients who had bacteremia/complicated MRSA infections were analyzed. The primary endpoint for clinical efficacy was an early clinical response at 72-96 h after the start of therapy. Five dosed of 12 mg/kg or 10 mg/kg was administered as an enhanced or conventional high loading dose regimen, respectively. The Cmin was obtained at 72 h after the first dose. RESULTS: Overall, 512 patients were eligible, and 76 patients were analyzed for treatment efficacy. The proportion of patients achieving the target Cmin range (20-40 µg/mL) by the enhanced regimen was significantly higher than for the conventional regimen (75.2% versus 41.0%, p < 0.001). In multivariate analysis, Cmin ≥ 20 µg/mL was an independent factor for an early clinical response (odds ratio 3.95, 95% confidence interval 1.25-12.53). There was no significant difference in the occurrence of adverse events between patients who did or did not achieve a Cmin ≥ 20 µg/mL. CONCLUSION: A target Cmin ≥ 20 µg/mL might improve early clinical responses during the treatment of difficult MRSA infections using 12 mg/kg teicoplanin for five doses within the initial 3 days.

Vancomycin loading dose is associated with increased early clinical response without attainment of initial target trough concentration at a steady state in patients with methicillin-resistant Staphylococcus aureus infections.

WHAT IS KNOWN AND OBJECTIVE: Vancomycin therapeutic guidelines suggest a loading dose of 25-30 mg/kg for seriously ill patients. However, high-quality data to guide the use of loading doses are lacking. We aimed to evaluate whether a loading dose (a) achieved a target trough concentration at steady state and (b) improved early clinical response. METHODS: Patients with an estimated glomerular filtration rate ≥ 90 mL/min/1.73 m2 were included. A loading dose of 25 mg/kg vancomycin followed by 15 mg/kg twice daily was compared with traditional dosing. A Cmin sample was obtained before the fifth dose. An early clinical response 48-72 hours after the start of therapy and clinical success at end of therapy (EOT) was evaluated in patients with methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant coagulase-negative Staphylococci or Enterococcus faecium. RESULTS: There was no significant difference in Cmin between the regimen with and without a loading dose (median: 10.4 and 10.2 µg/mL, P = .54). Proportions of patients achieving 10-20 and 15-20 µg/mL were 56.9% and 5.6%, respectively, in patients with a loading dose. Although there was no significant difference in success rate at EOT between groups, a loading dose was associated with increased early clinical response for all infections (adjusted odds ratio [OR]: 4.588, 95% confidence interval [CI]: 1.373-15.330) and MRSA infections (OR: 12.065, 95% CI: 1.821-79.959). Study limitations included no Cmin measurements within 24 hours and the inclusion of less critically ill patients. WHAT IS NEW AND CONCLUSION: A loading dose of 25 mg/kg followed by 15 mg/kg twice daily did not achieve the optimal Cmin at steady state in patients with normal renal function. However, more early clinical responses were obtained with a loading dose compared with traditional dosing, possibly because of a prompt albeit temporary achievement of a more effective concentration.

Pelvic alignment changes during the perinatal period.

BACKGROUND: The function of the pelvic bones is to transfer load generated by body weight. Proper function of the pelvic bones can be disturbed by alignment changes that occur during pregnancy. Further, misalignment of the pelvic bones can lead to pain, urinary incontinence, and other complications. An understanding of the timing and nature of pelvic alignment changes during pregnancy may aid in preventing and treating these complications. OBJECTIVE: To investigate the changes in pelvic alignment during pregnancy and one month after childbirth. METHODS: This is a prospective, longitudinal cohort study. Pelvic measurements were obtained for 201 women at 12, 24, 30, and 36 weeks of pregnancy, and 1 month after childbirth. The anterior and posterior width of the pelvis (the distance between the bilateral anterior superior iliac spines and the bilateral posterior superior iliac spines), the anterior pelvic tilt, and pelvic asymmetry (the mean left and right pelvic tilt degrees and the bilateral difference of the anterior pelvic tilt) were measured. For the change in pelvic alignment, a Friedman test was conducted to determine any significant difference in the measurements over time. RESULTS: The anterior and posterior width of the pelvis became significantly wider with pregnancy progress and the anterior width of the pelvis at 1 month after childbirth remained wider than that at 12 weeks of pregnancy (p < 0.001). The anterior pelvic tilt increased during pregnancy and decreased after childbirth (p < 0.05). CONCLUSION: Some changes in pelvic alignment occur continuously during the perinatal period. Changes in the anterior width of the pelvis are not recovered at one month post-childbirth. Understanding these perinatal changes may help clinicians avert complications due to pelvic misalignment.

The effects of pelvic belt use on pelvic alignment during and after pregnancy: a prospective longitudinal cohort study.

BACKGROUND: Pelvic alignment changes during pregnancy and post-childbirth. Pelvic belts exert external forces that compress and stabilize the joints, and therefore, could influence pelvic alignment. However, limited information is available regarding this potential effect. Therefore, the purpose of this study is to investigate the influence of pelvic belt use on pelvic alignment during and after pregnancy. METHODS: Data of 201 pregnant women in late pregnancy and 1 month after childbirth were used. Pelvic alignment measurements, including anterior and posterior pelvic width, pelvic asymmetry, and pelvic belt use during and after pregnancy were investigated. Participants were divided into four groups according to pelvic belt use: before and after childbirth (BAC), before childbirth only (BC), after childbirth only (AC), and non-use (NU). Then, an initial one-way ANOVA was conducted to compare the amount of change in pelvic alignment from late pregnancy to post-childbirth between the groups. After the initial analysis, a multivariate regression analysis was performed to determine the statistically significant differences between the groups to consider other factors that influenced pelvic alignment such as age, BMI, number of previous childbirths, vaginal delivery and pelvic asymmetry in late pregnancy. Next, a cutoff point for subgroup stratification based on the weekly duration of pelvic belt use and inter-group changes in pelvic alignment were compared. RESULTS: As the result of the initial one-way ANOVA, the decrease in pelvic asymmetry from during pregnancy to postpartum for BAC was greater than that for AC. Moreover, multiple regression analysis showed that the effect of pelvic belt that was revealed in the initial analysis was statistical significance even after adjustment for other factors. Moreover, pelvic asymmetry in the BAC group decreased, compared to being increased or unchanged in the NU and AC groups when the group cutoff time was 7 h per week. CONCLUSIONS: Continuous and extended use of pelvic belts during and after pregnancy might be related to modifications of pelvic asymmetry in the perinatal period. Therefore, the instruction of correct and comfortable usage and the recommendation of continuous use of pelvic belt especially during pregnancy are required for prevention of some discomforts related to pelvic malalignment.

The Association of Variations in Hip and Pelvic Geometry With Pregnancy-Related Sacroiliac Joint Pain Based on a Longitudinal Analysis.

STUDY DESIGN: Cross-sectional study using radiological measurements and longitudinal data analysis. OBJECTIVE: We aim to explore hip/pelvic geometry on anteroposterior radiographs and examine if such parameters are associated with clinical symptoms. SUMMARY OF BACKGROUND DATA: Pregnancy-related sacroiliac joint pain is a common disease and is responsible to the disability of daily activities. The etiology is likely to be correlated with the biomechanical factors which are determined by trunk load and hip/pelvic geometry. Previous studies have already found the association between symptoms and weight increase during pregnancy. However, the relationship between bony anatomy and pregnancy-related sacroiliac joint pain remains unknown. METHODS: In total, 72 women were included in the final analysis. In pregnant women with self-reported sacroiliac joint pain, pain scores at 12, 24, 30, and 36 weeks of pregnancy were recorded and included in a mixed-effect linear regression model as dependent variables. The radiological measurements were included as independent variables. Furthermore, to investigate the relationship between hip/pelvic geometry and the activity-specific nociceptive phenomenon, the radiological measurements between patients with and without activity-induced pain were compared using a binominal logistic regression model. RESULTS: The relative bilateral is chial tuberosity distance (betta coefficient: 0.078; P = 0.015) and the relative bilateral femoral head length (betta coefficient: 0.011; P = 0.028) showed significant interactions with the slope of pain scores. Moreover, women whose pain exacerbate during prolonged walking had a higher odds in hip/pelvic geometry of the bilateral ischial tuberosity distance (odds ratio [OR]: 1.12; P = 0.050) and the bilateral femoral head length (OR: 1.16; P = 0.076) with approximately significant P-value. CONCLUSION: These data indicate hip/pelvic anatomical variations are associated with the degree of pain increasing and the activity-specific pain during pregnancy, which may help to have further understanding on the biomechanical factor in developing pregnancy-related sacroiliac joint pain. LEVEL OF EVIDENCE: 3.

Low back pain and causative movements in pregnancy: a prospective cohort study.

BACKGROUND: Low back pain (LBP) during pregnancy might be strongly related to posture and movements of the body, and its management is a clinically important issue. The purpose of this study was to investigate the activities related to LBP during pregnancy. METHODS: Participants included 275 women before 12 weeks of pregnancy. The women were evaluated at 12, 24, 30, and 36 weeks of pregnancy. The intensity of LBP was assessed using the Numerical Rating Scale (NRS). Movements related to LBP were investigated by free descriptive answers. Descriptive statistics were used to compile the movements that pregnant women thought induced LBP at each evaluation. Subsequently, a linear regression analysis was performed to evaluate the degree of association of certain movements with LBP using the data of participants who had LBP. The intensity of LBP (NRS score) was specified as the dependent variable, the movements that were related to pain were specified as the independent variables at the analysis. A significance threshold was set at 0.05. RESULTS: The final sample used in the analyses was 254, 249, 258, and 245 women at 12, 24, 30, and 36 weeks of pregnancy, respectively. There were 16 kinds of movements that induced LBP and all of them were daily activities rather than special movements that require extra task or effort. As pregnancy progressed, less number of participants attributed pain to a specific movement. At all evaluations, movements, especially sitting up, standing up from a chair, and tossing and turning were thought to be related to LBP. Furthermore, standing up from a chair and tossing and turning were significantly related to LBP throughout the pregnancy. In contrast, lying down and sitting up were significantly related to LBP but the relationship did not continue till late pregnancy. CONCLUSIONS: Daily routine activity is related to LBP during pregnancy. These results suggest that recommendations for pregnant women about basic physical movements, such as ways of standing up that reduce the load on the body might be useful in the management of LBP.

High-dose regimen to achieve novel target trough concentration in teicoplanin.

In the treatment of severe MRSA infections such as endocarditis, more than 20 mg/L of plasma trough concentration (C(min)) is recommended for teicoplanin; however, in the treatment of common MRSA infections, recommended C(min) remains more than 10 mg/L. In this study, we set C(min) as 15-30 mg/L to obtain a favorable clinical outcome in the treatment of common MRSA infections, and investigated the optimal loading regimen that achieved the target C(min) in patients with normal renal function. Seventy-eight patients received the high-dose regimen A (6 mg/kg every 12-h for initial two days) and 60 patients received the high-dose regimen B (the first five loading doses of 10-12 mg/kg at 12-h intervals for initial three days, followed by 6 mg/kg once daily). The mean C(min) on the 4th day was 13.7 ± 5.3 mg/L in regimen A, and 20.0 ± 6.6 mg/L in regimen B (P < 0.001), and the proportion of patients achieving the 15-30 mg/L was 25.6% and 68.3% (P < 0.001). Clinical response at end-of treatment were 66.7% and 85.0% (P = 0.014). The patients of initial C(min) with ≥15 mg/L had tended to be higher clinical response than those with <15 mg/L (80.9% vs 68.6%, P = 0.084). There were no significant differences in the occurrence of adverse effects in regimen A and B (nephrotoxicity; 1.3% vs 3.3%, P = 0.413, hepatotoxicity; 5.1% vs 3.3%, P = 0.608). In conclusion, to obtain C(min) 15-30 mg/L, the first five loading doses of 10-12 mg/kg at 12-h intervals was required in patients with normal renal function.

Preferable timing of therapeutic drug monitoring in patients with impaired renal function treated with once-daily administration of vancomycin.

The aim of this study was to investigate the timing of therapeutic drug monitoring (TDM) in patients with impaired renal function treated with once-daily administration of vancomycin (VCM). Once-daily administration was selected for patients whose creatinine clearance (Ccr) was <80 ml/min. TDM was conducted on day 3 or on day 4. Adult patients whose VCM dosage was not altered according to initial C min and for whom subsequent follow-up TDM was performed within 1 week were entered into the study. Patients whose renal function deteriorated at follow-up TDM were excluded. One hundred sixty-five patients were eligible for analysis. Among patients with once-daily dosing, relative increases of C min at follow-up TDM compared with initial TDM were 34.5 ± 39.2 % in TDM on day 3 and 16.6 ± 20.6 % in TDM on day 4 (P = 0.016). In contrast, there was no significant difference in the relative increase of C min between TDM on days 3 and 4 (26.1 ± 39.6 vs. 18.4 ± 25.6 %, P = 0.551) in the twice-daily regimen. On multivariate analysis, TDM on day 3 alone (odds ratio, 4.93; 95 % confidence interval, 1.71-14.2) was selected as an independent risk factor associated with a relative increase of C min by >30 % in the once-daily regimen. Steady-state VCM serum concentration was not achieved on day 3 in the once-daily regimen in patients with impaired renal function, and TDM on day 3 caused underestimation of C min.

Evaluation of teicoplanin dosing designs to achieve a new target trough concentration.

Minimum inhibitory concentration (MIC) creep in vancomycin has prompted guidelines that recommend a target trough concentration (C (min)) of 15-20 mg/L, and it is also considered necessary to set a C (min) of >15 mg/L for teicoplanin (TEIC), especially in patients with complicated methicillin-resistant Staphylococcus aureus (MRSA) infections. The aim of this study was to investigate the appropriate TEIC regimen for reaching the revised target C (min) (15-30 mg/L) in patients with normal renal function and those with renal dysfunction. We analyzed patients with MRSA infections who were treated with TEIC between July 2006 and December 2009. Two-day loading regimen was studied in patients with non-renal-dysfunction (group 1). The 1-day loading regimen was studied in patients with non-renal-dysfunction (group 2, control) and in patients with renal dysfunction (group 3). The 178 patients in the study consisted of 76, 28, and 74 patients in groups 1, 2, and 3, respectively. C (min) on day 4 was 14.6 ± 5.6, 11.9 ± 4.1, and 13.5 ± 4.2 mg/L, and the proportion of patients achieving the revised target range was 34.2%, 17.9%, and 20.3%, respectively. Only one patient in group 1 revealed C (min) of >30 mg/L. Treatment success rates, nephrotoxicity, and hepatotoxicity were similar among the three groups. It was difficult to achieve the revised target C (min) with the 2-day loading regimen in patients without renal dysfunction and with the standard TEIC regimen, even in patients with renal dysfunction. Further investigation of an even higher TEIC dosing regimen is considered necessary.

Risk factors associated with the development of thrombocytopenia in patients who received linezolid therapy.

The major adverse event associated with linezolid treatment is thrombocytopenia. This study investigated risk factors associated with the development of thrombocytopenia in patients who received linezolid therapy. This was a retrospective study of patients treated with linezolid 600 mg q12h, by the oral or parenteral route, between July 2007 and June 2009. Thrombocytopenia was defined as a ≥ 10 × 104 cells/mm³ decrease from the baseline or a ≥ 30% reduction. Thirty-three variables were analyzed as risk factors associated with thrombocytopenia. Multivariate analysis was performed with SPSS version 16 software. This study included 331 patients (221 male, 58.0 ± 20.2 years). The mean duration of linezolid therapy was 10.5 ± 8.7 days. Thrombocytopenia occurred in 128 patients (38.7%), of whom 21 required platelet transfusion. Thrombocytopenia developed 7.4 ± 4.8 days after linezolid initiation, and the platelet count recovered 12.3 ± 7.8 days after withdrawal. In the final steps of stepwise logistic regression analysis, 5 variables were selected: duration of linezolid therapy ≥ 14 days [odds ratio (OR) 3.04, 95% confidence interval (CI) 1.73-5.34, P < 0.001], creatinine clearance < 50 mL/min (OR 2.32, 95% CI 1.45-3.74, P < 0.001), chronic liver disorders (OR 1.63, 95% CI 0.92-2.86, P = 0.092), and respiratory tract infections (OR 1.75, 95% CI 1.05-2.91, P = 0.031). In contrast to findings with parenteral administration, oral administration of linezolid decreased the risk of thrombocytopenia (OR 0.38, 95% CI 0.15-0.97, P = 0.042). The time to the onset of thrombocytopenia in patients with creatinine clearance <50 mL/min was significantly shorter than that in patients with creatinine clearance ≥ 50 mL/min (6.7 ± 4.4 and 8.5 ± 5.2 days, P = 0.039), and in patients administered orally the time to the onset of thrombocytopenia was 10.4 ± 6.6 days. Several factors influenced the occurrence of linezolid-induced thrombocytopenia. Dose adjustment may be required in at-risk patients, especially those with renal dysfunction.

Clinical characteristics of vancomycin minimum inhibitory concentration of 2 µg/ml methicillin-resistant Staphylococcus aureus strains isolated from patients with bacteremia.

Recent studies demonstrated that mortality associated with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia was high when vancomycin was used to treat infections with strains that had a high vancomycin minimum inhibitory concentration (MIC). This study compared several characteristics of vancomycin MIC 2 µg/ml strains isolated from bacteremia with those isolated from infections other than bacteremia. A total of 128 episodes of MRSA bacteremia between 2005 and 2008 were followed-up, and compared with 631 MRSA infections other than bacteremia. The isolation of strains with a 2 µg/ml MIC accounted for 32.0% of isolates from MRSA bacteremia, whereas strains with a 2 µg/ml MIC comprised 9.0% of MRSA isolated from other sites (p < 0.001). The incidence of pneumonia as the source of infection was significantly higher in patients with bacteremia from strains with a 2 µg/ml MIC than in those with ≤1 µg/ml MIC. Prior vancomycin use did not correlate with the isolation of 2 µg/ml strains. The efficacy of glycopeptides as 1st line therapy in patients infected with 2 µg/ml strains was significantly lower than that for patients infected with ≤1 µg/ml strains (30.0 vs. 78.8%, p < 0.001) in bacteremia. In the analysis of infections other than bacteremia, efficacy did not reveal a significant difference according to MIC (69.0 vs. 79.6%, p = 0.109). In bacteremia, mortality was 65.8% in patients with 2 µg/ml strains and 19.5% in patients with ≤1 µg/ml strains (p < 0.001), whereas there was no significant difference in mortality from infections other than bacteremia (10.7 vs. 7.8%, p = 0.617). In multivariate analysis, bacteremia with 2 µg/ml strains, intensive care unit (ICU) stay, and liver cirrhosis were independent risk factors for death in patients with bacteremia, and initial appropriate therapy lowered the risk. Several characteristics such as a higher incidence than at other infection sites, a high incidence of pneumonia as a source of infection, a low success rate of vancomycin therapy, and poor prognosis were confirmed in 2 µg/ml MIC MRSA isolated from bacteremia; however, a low success rate of vancomycin and poor prognosis were not apparent in 2 µg/ml MIC MRSA strains isolated from infections other than bacteremia.

[Quality evaluation of magnesium oxide tablets using acid neutralization test and dissolution test].

For the purpose of quality evaluation of commercially available magnesium oxide (MgO) tablets, we studied their acid neutralization and dissolution behaviors. The dissolution test was carried out by the paddle method in 1st fluid (pH 1.2). The dissolution amount of MgO from tablets was determined by chelatometric titration. The medium pH was periodically measured. The neutralization reaction in 750 ml of 1st fluid was markedly different between two kinds of commercial tablets. The pH of medium including Magmit tablet reached 8.9 and the dissolution rate of MgO was 81.1% after 20 min. Contrariwise, the final pH of medium including Maglax tablet was 2.5 and the dissolution rate of MgO was 77.1% after 60 min. These results indicate that the dissolution rate of MgO from tablets should be >81.1% to obtain significant acid neutralization action.