Association between the hypokalaemia index based on area over the serum potassium concentration curve and occurrence of acute kidney injury in patients administered liposomal amphotericin B.

BACKGROUND: Acute kidney injury (AKI) and hypokalaemia are common adverse events after treatment with liposomal amphotericin B (L-AMB). OBJECTIVES: Because excess potassium (K) leakage occurs during renal tubular injury caused by L-AMB, measuring the decrease in rate of serum K concentration might be more useful to assess the renal impact of L-AMB than hypokalaemia identified from a one-point measurement. The effects of a decrease in K concentration and duration of hypokalaemia on AKI were investigated. METHODS: A ≥ 10% decrease in K concentration from the reference concentration within a 7-day timeframe was evaluated. The hypokalaemia index, which combines the duration of K concentration lower than the reference and a marked low K concentration, was calculated from the area over the concentration curve. RESULTS: Eighty-six patients were included in the study. The incidences of AKI and decrease in K concentration were 36.0% and 63.9%, respectively. Of patients who developed both adverse events, a decrease in K concentration occurred first in 22 of 26 patients, followed by AKI 7 days later. Hypokalaemia did not increase AKI risk whereas a decrease in K concentration was an independent risk factor for AKI. The hypokalaemia index in patients with AKI was significantly higher than those without AKI (5.35 vs. 2.50 points, p = 0.002), and ≥3.45 points was a significant predictor for AKI. CONCLUSION: A ≥ 10% decrease in the K concentration was a significant factor for AKI in patients receiving L-AMB therapy. In such patients, dose reduction or alternative antifungals could be considered based on the hypokalaemia index.

Association between preoperative biologic use and surgical morbidity in patients with Crohn's disease.

PURPOSE: We evaluated the influence of preoperative treatments with biologics on surgical morbidity in patients with Crohn's disease (CD). METHODS: We reviewed the surveillance data of patients with CD who underwent surgery between April 2018 and April 2021. The possible risk factors for morbidity were analyzed. RESULTS: A total of 305 surgically treated patients were included. Anti-TNF alpha agents and ustekinumab were used in 92 and 27 patients, respectively, within 12 weeks before surgery. There were no cases of mortality. In total, 70/305 (23.0%) patients developed a complication, and 42/305 (13.8%) patients developed a surgical site infection (SSI) (17 incisional SSIs and 35 organ/space SSIs). Current smoking status (OR 3.44), emergent/urgent surgery (OR 6.85), and abdominoperineal resection (APR) (OR 14.93) were identified as risk factors for total complications. Penetrating disease (OR 14.55) was identified as a risk factor for incisional SSIs. Current smoking status (OR 7.09), an American Society of Anesthesiologists (ASA) score greater than 3 (OR 5.85), a postoperative blood sugar level over 155 mg/dL (OR 4.37), and APR (OR 207.95) were identified as risk factors for organ/space SSIs. CONCLUSIONS: No correlation between preoperative treatment with biologics and surgical mortality or morbidity was found. However, we should perform further analyses on a larger number of patients because the analyses may be limited by selection bias for treatment and several confounding factors.

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.

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.

Improvement in Hyperglycemia Prevents Surgical Site Infection Irrespective of Insulin Therapy in Non-diabetic Patients Undergoing Gastrointestinal Surgery.

BACKGROUND: Intensive glycemic control is recommended to prevent surgical site infections (SSI). Our aim was to evaluate retrospectively the effect of improvement in hyperglycemia irrespective of insulin use on the incidence of SSI in non-diabetic patients. METHODS: The highest blood glucose (BG) concentration within 12 h (early peak BG) and the final BG from 12 to 24 h after surgery were evaluated in patients who underwent gastrointestinal surgery. Patients with an early peak BG of ≥150 mg/dL were divided into those with persistent (final BG of ≥150 mg/dL) and improved hyperglycemia (final BG of <150 mg/dL). Patients without hyperglycemia and those with late-onset hyperglycemia were also assessed for SSI risk. RESULTS: Overall, 1612 patients were studied (diabetes, n = 293). Although hyperglycemia increased the SSI rates in non-diabetic patients, no correlation was demonstrated in patients with diabetes at any cutoff final BG defining htperglycemia except for 180 mg/dL. Hyperglycemia improved without insulin therapy in 283 of 512 non-diabetic patients who had early hyperglycemia. The adjusted standardized residual for those with SSI and persistent hyperglycemia was 5.2 (P < 0.05). In contrast, the absence of hyperglycemia was a significant preventive factor for SSI. In the multivariate analyses, persistent hyperglycemia was an independent risk factor for SSI (odds ratio 1.54; 95% confidence interval 1.03-2.31). CONCLUSIONS: Remission of hyperglycemia within 24 h after surgery prevented SSI in non-diabetic patients. Considering that hyperglycemia improved in approximately half of patients without insulin therapy, commencement of insulin dosing after two consecutive BGs of ≥150 mg/dL might be reasonable, especially in general wards.

Sensitivity and specificity of different antibody tests for detecting varicella-zoster virus.

INTRODUCTION: Antibody tests for detecting varicella-zoster virus include the fluorescent-antibody-to-membrane-antigen (FAMA) assay, immune adherence hemagglutination assay (IAHA), enzyme immunoassay (EIA), and the glycoprotein-based enzyme-linked immunosorbent assay (gpELISA). Although FAMA and gpELISA are highly sensitive, FAMA is not available commercially. Therefore, this study was performed to compare potential high-sensitivity tests with commercially available tests. METHODS: Four antibody tests, FAMA, gpELISA, EIA, and IAHA, were performed using sera collected from 32 children aged 7 months-10 years. Using FAMA as a reference, the sensitivity and specificity of gpELISA, EIA, and IAHA were assessed. Subsequently, using gpELISA as a reference, the positive agreement rate of EIA and IAHA was assessed. RESULTS: On a reference scale with FAMA set at 100%, the sensitivity and specificity of the antibody tests were as follows: gpELISA, 67% and 100%; EIA, 67% and 100%; and IAHA, 47% and 100%, respectively. The positive agreement rates of EIA and IAHA relative to gpELISA were 86% and 64%, respectively. CONCLUSIONS: gpELISA had a lower positive rate than did FAMA, and showed comparable sensitivity to that of EIA.

Clinical efficacy of teicoplanin in the treatment of bloodstream infection caused by methicillin-resistant coagulase-negative staphylococci.

Empirical combination therapy with ß-lactams and glycopeptides is recommended for patients with presumed staphylococcal bloodstream infection (BSI). While coagulase-negative staphylococci (CNS) remain susceptible to vancomycin, such isolates have become less susceptible to teicoplanin. The aim of this retrospective study was to evaluate the clinical efficacy of teicoplanin in the treatment of BSI caused by methicillin-resistant CNS according to teicoplanin susceptibility. Inclusion criteria were patients with intravascular-catheter related BSIs caused by methicillin-resistant CNS (positive for two or more specimens); teicoplanin therapy; and at least one of the signs or symptoms caused by BSI. Antimicrobial resistance was defined as minimum inhibitory concentration (MIC) ≥8 µg/mL. The primary efficacy endpoint was clinical success evaluated 2 weeks after the completion of teicoplanin therapy [test of cure (TOC)]. Resistant rate of CNS was 0% for vancomycin and 22.9% for teicoplanin, and geometric mean MICs were 1.31 µg/mL and 3.41 µg/mL, respectively (p < 0.001). The catheter was removed in all patients except one, and high early clinical response at 72 h after starting therapy was obtained irrespective of teicoplanin susceptibility. The clinical success rate at TOC was 60% in patients with BSIs caused by teicoplanin-resistant strains, while 90% in patients with BSIs caused by susceptible strains (p = 0.052). In multivariate analyses, teicoplanin resistance was significant factor for decreased clinical success at TOC (adjusted odds ratio 0.138, 95% confidence interval 0.020-0.961, p = 0.045). Because of the poor clinical efficacy of teicoplanin against teicoplanin-resistant CNS, combination therapy comprising vancomycin and ß-lactam antibiotics should be considered in presumed staphylococci BSI.

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.

Evaluation of influenza vaccine-induced cell-mediated immunity: Comparison between methods using peripheral blood mononuclear cells and whole blood.

Assessment of cell-mediated immunity (CMI) may be critical to evaluating the ability of individuals to protect themselves against influenza virus infection. However, it has been difficult to evaluate CMI because no simple means of measuring it is currently available. The aim of this study was to compare the performance of a CMI measurement method developed by us, which involves reacting whole blood with antigen, with the conventional method, which is based on isolating peripheral blood mononuclear cells (PBMCs). Correlations between these methods before and after vaccination of 26 healthy adults (aged 28-58 years; 12 men and 14 women) were assessed and changes in CMI after influenza vaccination in PBMCs cultured with antigen for 48 and 96 hr and whole blood cultured with antigen for 48 hr were studied. Results of CMI measurement using whole blood on Day 2 and PBMCs on Day 4 were found to be correlated. Spearman's correlation coefficients with four antigens (A [H1N1], A [H3N2], B [Yamagata lineage], and B [Victoria lineage]) before vaccination were 0.55, 0.61, 0.58, and 0.70, respectively and 0.40, 0.45, 0.62, and 0.52, respectively, after vaccination. CMI was detected sooner when whole blood was reacted with antigen than when PBMCs were reacted with antigen. The rate of positive reaction of influenza A (H1N1 and H3N2) in whole blood on Day 2 was higher than that in PBMCs on Day 2. Our method is simple and may be useful for vaccine development because it can measure CMI in a small amount of blood without separating off PBMCs.

Associations between multiple immunosuppressive treatments before surgery and surgical morbidity in patients with ulcerative colitis during the era of biologics.

PURPOSE: It is unclear whether immunomodulators or biologics, with the exception of corticosteroids, can be risk factors for postoperative infectious complications of ulcerative colitis (UC). Moreover, many immunosuppressive therapies including some biologics are used mainly to treat UC, and many patients are on multi-agent immunosuppressive therapy at the time of surgery. Therefore, we evaluated the influence of pre-operative multiple immunosuppressive agents on the occurrence of surgical site infection (SSI) in UC during the era of biologics. METHODS: We reviewed surveillance data from 301 patients who underwent surgery between January 2015 and April 2018. The incidences of SSI and possible risk factors among patients receiving different immunosuppressive therapies were compared and analyzed. RESULTS: The incidence of incisional SSI was 6.6%, and that of organ/space SSI was 7.0%. Doses of corticosteroids were significantly decreased because of the recent shift toward the use of biologics. The types and numbers of immunosuppressive agents did not significantly correlate with each incidence. Age ≥ 65 years (odds ratio (OR) 3.0), total prednisolone dose ≥ 9000 mg (OR 2.7), and perioperative blood transfusion (OR 3.6) were shown to be independent risk factors for incisional SSI, whereas duration of surgery ≥ 252 min (OR 3.8), urgent/emergent surgery (OR 2.9), and perioperative blood transfusion (OR 2.6) were identified as independent risk factors for organ/space SSI. CONCLUSIONS: Although no correlation between pre-operative immunosuppressive therapies, except for corticosteroids, was found, selection bias may have occurred due to treatment before surgery. However, biologics, calcineurin inhibitors, and thiopurines did not affect surgical morbidity in UC.

Risk factors for surgical site infection after major hepatobiliary and pancreatic surgery.

Major hepatobiliary and pancreatic (HP) surgeries are complex procedures associated with a high incidence of surgical site infection (SSI) and are commonly performed in patients with cancer in Japan. This study was performed to investigate the risk factors for SSI, including incisional and organ/space SSI, in HP surgery. The following procedures were included in the study: hepatectomy with and without biliary tract resection, pancreatectomy [pancreaticoduodenectomy (PD), others], and open cholecystectomy. In total, 735 patients were analyzed. The incidence of SSI was 17.8% (incisional, 5.2%; organ/space, 15.5%; both 2.9%). The highest incidence of SSI was observed in patients who underwent hepatectomy with biliary tract resection (39.1%), followed by pancreatectomy (PD, 28.8%; others, 29.8%). Almost all SSIs after these three procedures were classified as organ/space (39.1%, 25.0%, and 27.7%, respectively), and these procedures were risk factors for not only total SSI but also organ/space SSI in the multivariate analysis. An American Society of Anesthesiologists physical status of ≥3 was a risk factor for incisional SSI. Preoperative biliary drainage, prolonged surgery, concomitant surgery, and massive intraoperative bleeding were associated with SSI. In conclusion, the main type of SSI was organ/space SSI after HP surgery, and different risk factors were identified between organ/space and incisional SSI. Procedure-related factors and preoperative biliary drainage were independent risk factors for SSI. To prevent SSI, the indication for preoperative biliary drainage should be carefully evaluated in patients undergoing HP surgery.

Evaluation of influenza vaccine-immunogenicity in cell-mediated immunity.

The immunological effect of influenza vaccines cannot be evaluated accurately using an antibody titer. Therefore, we used a new method that measures cell-mediated immunity to investigate changes in the amount of interferon-gamma (IFN-γ) produced after vaccination in response to the vaccine antigen. The study was conducted during the 2014-2015 influenza season in 23 adults, using a vaccine that contained three types of antigen. The IFN-γ level increased by at least 1.5 times in 65% (15/23) of cases in response to the H1N1 antigen, in 57% (13/23) of cases in response to the H3N2 antigen, and in 57% (13/23) of cases in response to the B antigen. During the study period, 4 subjects developed type A influenza. Our data showed that the IFN-γ level did not increase by 1.5 times in these subjects. We propose that the efficacy of influenza vaccines may be evaluated by measuring changes in the level of IFN-γ produced in response to influenza vaccine.

Catheter-associated bloodstream infection after bowel surgery in patients with inflammatory bowel disease.

PURPOSE: Catheter-associated bloodstream infections (CABSIs) are a leading cause of nosocomial infections. The objectives of this study were to establish the incidence of CABSIs after bowel surgery and to identify the risk factors. METHODS: We reviewed the prospectively collected data of patients who underwent abdominal surgery with central venous catheter (CVC) insertion between March, 2006 and September, 2009. We analyzed all possible variables, including age, sex, disease, CVC duration, insertion frequency, CVC site, infliximab, corticosteroid, and immunosuppressant administration, preoperative serum albumin level, surgical wound class, and emergency surgery. RESULTS: A total of 1261 patients were prospectively surveyed. The underlying diseases comprised ulcerative colitis (UC; n = 428), Crohn's disease (CD; n = 334), colorectal cancer (CA; n = 344), esophageal cancer (ESO; n = 28), gastric cancer (GAST; n = 44), and others (n = 83). The incidences of CABSI were 6.9/1000 catheter days for UC, 7.4 for CD, 4.3 for CA, 3.7 for ESO, 3.7 for GAST, and 5.1 for others. CD patients had the highest rate of CABSI. The risk factors for CABSI were CD with an odds ratio (OR) of 1.63, dirty/infected wound class (OR 3.34), and CVC insertion via the internal jugular vein (OR 9.89). CONCLUSION: A high CABSI incidence was found in association with CD, especially in dirty/infected surgery. Thus, the use of CVCs should be restricted in the presence of these risk factors.

Timing of Assessment of Humoral and Cell-Mediated Immunity after Influenza Vaccination.

Assessment of the immune response to influenza vaccines should include an assessment of both humoral and cell-mediated immunity. However, there is a lack of consensus regarding the timing of immunological assessment of humoral and cell-mediated immunity after vaccination. Therefore, we investigated the timing of immunological assessments after vaccination using markers of humoral and cell-mediated immunity. In the 2018/2019 influenza season, blood was collected from 29 healthy adults before and after vaccination with a quadrivalent inactivated influenza vaccine, and we performed serial measurements of humoral immunity (hemagglutination inhibition [HAI] and neutralizing antibody [NT]) and cell-mediated immunity (interferon-gamma [IFN-γ]). The HAI and NT titers before and after vaccination were strongly correlated, but no correlation was observed between the markers of cell-mediated and humoral immunity. The geometric mean titer and geometric mean concentration of humoral and cellular immune markers increased within 2 weeks after vaccination and had already declined by 8 weeks. This study suggests that the optimal time to assess the immune response is 2 weeks after vaccination. Appropriately timed immunological assessments can help ensure that vaccination is effective.

Risk factors for surgical site infection and association with infliximab administration during surgery for Crohn's disease.

BACKGROUND: Preoperative infliximab treatment may influence postoperative infectious complications in patients with Crohn's disease. OBJECTIVE: The aim of this study was to identify predictors of surgical site infection after surgery for Crohn's disease and evaluate the effects of preoperative infliximab administration. DESIGN: We performed a prospective surveillance and review of surgical site infections. SETTINGS: This study was conducted in the Surgical Department of Hyogo College of Medicine. PATIENTS: A total of 405 consecutive patients with Crohn's disease who underwent abdominal surgery between January 2008 and December 2011 were included. MAIN OUTCOME MEASURES: Infection was diagnosed by the infection control team. The possible risk factors were analyzed by using logistic regression analyses to determine their predictive significance. RESULTS: Within the patient population, 20% of patients received infliximab, and 60% had penetrating disease. The median duration from the last infliximab infusion to surgery was 43 days (range, 4-80). The overall incidence of surgical site infection was 27%. The incidence of incisional surgical site infection was 18%, and the organ/space surgical site infection rate was 8%. In the multivariate analysis, proctectomy was the highest risk factor for all surgical site infection (OR, 3.4-11.8; p < 0.01). The administration of preoperative infliximab was not a risk factor for surgical site infection. By contrast, there was a significantly reduced risk of incisional surgical site infection in patients with penetrating disease who received infliximab (OR, 0.1; p < 0.01). LIMITATIONS: This study was a cohort study and not a randomized trial. The data analyses were performed for surgical site infections but not for other infectious complications. CONCLUSIONS: Proctectomy was a high-risk factor for surgical site infection in patients with Crohn's disease. The administration of preoperative infliximab was not a risk factor for surgical site infection.

Infliximab administration prior to surgery does not increase surgical site infections in patients with ulcerative colitis.

PURPOSE: The high incidence of infectious complications in ulcerative colitis (UC) is generally recognized to be due to several factors related to a compromised host. In our previous study, a high dose of corticosteroid was shown to be a risk factor for surgical site infection (SSI). Recently, infliximab (IFX) has been used for refractory UC. In this study, the effect of IFX on the occurrence of infectious postoperative complications for UC was evaluated, because it remains controversial. METHOD: A total of 196 UC patients who underwent laparotomy between January 2010 and September 2012 were included. Possible factors related to complications were analyzed to identify significant predictors. RESULTS: Twenty-two patients had IFX before surgery. The overall incidence of SSI was 47/196 (24.0 %). The incidence of infections, including SSI and other infections, was 69/196 (35.2 %). On multivariate analysis, national nosocomial infection surveillance (NNIS) risk index ≥2 (p<0.01) and preoperative prednisolone dose ≥0.2 mg/kg/day (p = 0.01) were identified as independent risk factors for overall SSI; NNIS risk index ≥2 (p <0.01) and duration from onset of UC ≥6.3 years (p = 0.045) were identified as independent risk factors for incisional SSI; contaminated wound class (p <0.01), preoperative hospital stay ≥6 days (p = 0.048), severe/fulminant disease activity (p = 0.04), and pancolitis (p = 0.02) were identified as independent risk factors for organ/space SSI; and contaminated wound (p < 0.01), severe/fulminant disease activity (p = 0.02), and age at surgery ≥43 years (p = 0.047) were identified as independent risk factors for total infectious complications. CONCLUSION: IFX administration was not associated with infectious complications for UC surgery.

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.

Comparison of the Hemagglutination Inhibition Titers against Influenza Vaccine Strains in Japan from the 2017/2018 to 2021/2022 Seasons Using a Single Set of Serum Samples.

In Japan, inactivated influenza vaccines are used. We measured titers of antibodies to vaccine strains of three influenza types-influenza A (H1N1), influenza A (H3N2), and influenza B/Victoria-from the 2017/2018 to 2021/2022 seasons, but not for influenza A (H3N2) from the 2018/2019 season, using a single set of serum samples from 34 healthy volunteers, and assessed the consistency in antibody positivity between seasons. The antibody titers in the 2017/2018 season were used as a reference. The influenza A (H1N1) antibody titer in 2019/2020 did not differ significantly from that in the 2017/2018 season, but the titers varied in the two subsequent seasons. The influenza A (H3N2) antibody titers toward the 2019/2020, 2020/2021, and 2021/2022 seasonal viruses differed significantly from that in the 2017/2018 season. The influenza B/Victoria antibody titer toward the 2019/2020 seasonal antigen differed from that in the 2017/2018 season, and the antibody positivity was inconsistent between seasons; however, the antibody titer in the 2020/2021 season did not differ significantly from those in the prior two seasons, and the antibody positivity was consistent between seasons. Antibody titers and their consistency can be used to evaluate cross-immunity of antibodies.

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.