Higher Serum Trough Research Articles

Vancomycin nephrotoxicity: A comprehensive clinico-pathological study.

Vancomycin, a commonly prescribed antibiotic particularly in the setting of multi-drug resistant infections, is limited by its nephrotoxicity. Despite its common occurrence, much remains unknown on the clinicopathologic profile as well as the pathogenesis of vancomycin nephrotoxicity. Clinical studies included patients often with severe comorbidities and concomitant polypharmacy confounding the causal pathogenesis. Animal models cannot recapitulate this complex clinical situation. Kidney biopsy was not commonly performed. To address this limitation, we studied 36 patients who had renal biopsies for acute kidney injury (AKI) for suspicion of vancomycin nephrotoxicity. Detailed renal biopsy evaluation, meticulous evaluation of clinical profiles, and up-to-date follow-up allowed for a diagnostic categorization of vancomycin nephrotoxicity (VNT) in 25 patients and absence of vancomycin nephrotoxicity (NO-VNT) in 11 patients. For careful comparison of these two groups, we proceeded to compile a clinicopathologic and morphologic profiles characteristic for each group. Patients with VNT had a characteristic clinical profile including a common clinical background, a high serum trough level of vancomycin, a rapidly developed and severe acute kidney injury, and a recovery of renal function often shortly after discontinuation of vancomycin. This clinical course was correlated with characteristic renal biopsy findings including acute tubulointerstitial nephritis of allergic type, frequent granulomatous inflammation, concomitant and pronounced acute tubular necrosis of nephrotoxic type, and vancomycin casts, in the absence of significant tubular atrophy and interstitial fibrosis. This clinico-pathologic profile was different from that of patients with NO-VNT, highlighting its role in the diagnosis, management and pathogenetic exploration of vancomycin nephrotoxicity. Vancomycin nephrotoxicity has a distinctive morphologic and clinical profile, which should facilitate diagnosis, guide treatment and prognostication, and confer pathogenetic insights.

Vancomycin-induced nephrotoxicity in non-intensive care unit pediatric patients

Previous data suggested several risk factors for vancomycin-induced nephrotoxicity (VIN), including higher daily dose, long-term use, underlying renal disease, intensive care unit (ICU) admission, and concomitant use of nephrotoxic medications. We conducted this study to investigate the prevalence and risk factors of VIN and to estimate the cut-off serum trough level for predicting acute kidney injury (AKI) in non-ICU pediatric patients. This was a retrospective, observational, single-center study at Samsung Medical Center tertiary hospital, located in Seoul, South Korea. We reviewed the medical records of non-ICU pediatric patients, under 19 years of age with no evidence of previous renal insufficiency, who received vancomycin for more than 48 h between January 2009 and December 2018. The clinical characteristics were compared between patients with AKI and those without to identify the risk factors associated with VIN, and the cut-off value of serum trough level to predict the occurrence of VIN was calculated by the Youden’s index. Among 476 cases, 22 patients (4.62%) developed AKI. The Youden’s index indicated that a maximum serum trough level of vancomycin above 24.35 μg/mL predicted VIN. In multivariate analysis, longer hospital stay, concomitant use of piperacillin-tazobactam and serum trough level of vancomycin above 24.35 μg/mL were associated independently with VIN. Our findings suggest that concomitant use of nephrotoxic medication and higher serum trough level of vancomycin might be associated with the risk of VIN. This study suggests that measuring serum trough level of vancomycin can help clinicians prevent VIN in pediatric patients.

A phase 2 study of E6011, an anti-Fractalkine monoclonal antibody, in patients with rheumatoid arthritis inadequately responding to biological disease-modifying antirheumatic drugs

Objectives To evaluate the safety and efficacy of E6011, a novel humanized anti-fractalkine monoclonal antibody, in patients with active rheumatoid arthritis (RA) with an inadequate response to biological disease-modifying antirheumatic drugs (DMARDs). Methods Active RA patients inadequately responding to biological DMARDs were randomly assigned to placebo or E6011 400-mg group at a 1:1 ratio, and administered E6011 at weeks 0, 1, 2, and subsequently every 2 weeks. Primary endpoint was American College of Rheumatology (ACR)20 response at week 12. Results Of 64, 33 received placebo, 31 received E6011 400-mg. The ACR20 response rate at week 12 (non-responder imputation) was 27.3% and 22.6% in the placebo and E6011 groups, respectively. ACR50, ACR70 response rates at week 12 were 3.0%, 0% in the placebo and 9.7%, 3.2% in the E6011 group. Exploratory PK exposure analysis revealed that the effect of E6011 tended to be clearer in patients with higher serum trough E6011 concentration. E6011 was well tolerated with no notable safety concerns. Conclusions E6011 400-mg was well tolerated but had no clear efficacy at week 12 in RA patients with inadequate response to biologics. Further investigations are warranted to determine the optimal clinical dose and evaluation period for E6011.

Safety and efficacy of current gentamicin dosing schedules used in neonates in Sri Lanka

Introduction: Gentamicin is the first line antibiotic for early onset neonatal sepsis. Yet the problem with gentamicin is the low therapeutic index. It is known that high trough levels correlate with ototoxicity and nephrotoxicity while the peak levels decide the therapeutic effect. Once daily dose (ODD) and twice daily dose (TDD) schedules are practised in neonatal units in Sri Lanka. Objectives: To assess whether the ODD and TDD schedules of gentamicin used in neonates are effective in avoiding high serum trough levels and in achieving peak serum levels in the therapeutic range. Method: A prospective study was conducted from April to August 2017 in four neonatal units on term neonates less than one week old, in whom gentamicin was started (TDD regime= 2.5 mg/kg 12 hourly and ODD regime= 5mg /kg 24 hourly) during the study period. Trough and peak serum gentamicin levels (SGLs) were assessed before and after the third dose in the TDD regime and after the second dose in the ODD regime. Serum creatinine (SCr) was measured in all the neonates and neonates with high trough levels were referred for hearing assessment. Results: A total of 50 neonates of clinical maturity 37-41 weeks and birth weight 1.8-4.1 kg was included. High trough levels (>2 mg/dl) were seen in 48% of the TDD group and in 12% of the ODD group (p=0.005) Mean trough value in the ODD group was 1.15 mg/dl (SD 0.87) and in the TDD group was 2.14 mg/dl (SD 1.72). (T=-2.564, df=35, p = 0.015). Peak SGL in the therapeutic range (5-10 mg/dl) was seen in 92% of ODD regime and in 80% of the TDD regime. Mean peak values in the ODD and TDD regimes were 9.42 (SD 2.37) mg/dl and 7.12 (SD 2.18) mg/dl respectively (T= 3.56, df=48, p = 0.001). SCr and the hearing assessment were within normal limits in all neonates. Conclusions: The ODD gentamicin schedule of 5 mg/kg achieves a significantly higher peak serum gentamicin level and safer trough levels than the TDD schedule of 2.5 mg/kg.

Tissue Drug Concentrations of Anti-tumor Necrosis Factor Agents Are Associated with the Long-term Outcome of Patients with Crohn's Disease.

Many reports indicate that a high-serum trough level of anti-tumor necrosis factor (TNF) agents is required for sustained remission in patients with Crohn's disease The pharmacokinetics of anti-TNF agents in inflamed intestinal tissue, however, is not well investigated. We investigated the association between the tissue concentration of anti-TNF agents and long-term disease outcome. This was a prospective single-center study that enrolled 25 patients with Crohn's disease who were administered infliximab or adalimumab. All participants underwent endoscopy 2 weeks after administration of the anti-TNF agents, and biopsy samples were obtained from both inflamed and noninflamed intestinal tissue. Tissue concentrations of anti-TNF agents were evaluated and the correlation with serum trough levels was compared. The relation between the tissue drug concentration and clinical course over 24 months was also investigated. Concentrations of anti-TNF agents were significantly higher in inflamed tissue than in noninflamed tissue. Patients with high-serum trough concentrations of anti-TNF agents had significantly higher drug levels in the noninflamed tissue than those with low-serum trough concentrations, but no difference in the levels was detected in the inflamed tissue. Patients with high-drug levels in the noninflamed tissue had a significantly higher sustained response rate than patients with low-drug levels. Concentrations of anti-TNF agents in the noninflamed tissue can reflect sustained remission and may be a useful biomarker for monitoring therapeutic intensity in patients with Crohn's disease treated with anti-TNF agents (see Video Abstract, Supplemental Digital Content 1, http://links.lww.com/IBD/B623).

P419 Concentrations of anti-TNF agents in non-inflamed intestinal tissue are associated with the long-term outcome of patients with Crohn's disease

Background: Many reports show that high serum trough levels of anti-tumor necrosis factor (TNF) agents are required for the sustained remission in patients with Crohn's disease (CD). However, the pharmacokinetics of anti-TNF agents in intestinal mucosa was poorly investigated. The aim of our study was to investigate the correlation between the tissue concentration of anti-TNF agents and long-term disease outcome. Methods: This was a prospective single center study and 25 patients with CD administered infliximab or adalimumab as a maintenance therapy were enrolled. All participants received colonoscopy or balloon-assisted small bowel endoscopy two weeks after the administration of anti-TNF agents. Biopsy samples obtained from the inflamed and non-inflamed intestinal tissue were immersed in distilled water in the concentration of 0.1 mg/ μl. Tissue concentrations of anti-TNF agents were evaluated by enzyme-linked immunosorbent assay and the correlation with serum trough levels was compared. Moreover, we investigated the association between tissue concentrations of anti-TNF agents and the time to therapeutic interventions defined as no additional medical, endoscopic, and surgical treatment for 24 months. Results: Concentrations of anti-TNF agents in the inflamed tissue were significantly higher than that in the non-inflamed tissue (1.7 versus 1.0 μg/g, median, p=0.0011). Crohn's Disease Activity Index score and modified Rutgeerts score were not associated with the levels of anti-TNF agents in either inflamed or non-inflamed tissue. Serum trough concentrations of infliximab and adalimumab were 2.3 μg/ml (median, range [0.2–7.0]) and 10.4 μg/ml (0.8–22.8), respectively. When the patients were divided by median serum trough levels of each anti-TNF agent, patients with high serum trough concentrations of anti-TNF agents had significantly higher anti-TNF agents levels in the non-inflamed tissue than those with low serum trough concentrations (1.2 versus 0.0 μg/g, median, p=0.0346), but the difference was not observed in the inflamed tissue. Patients with high concentrations of anti-TNF agents in the non-inflamed tissue (>1.3 μg/g) had significantly longer time to therapeutic interventions than those with low concentrations of anti-TNF agents (15.5 versus 3.0 months, HR 0.33; 95% CI: 0.09–0.93). Conclusions: The concentrations of anti-TNF agents in the non-inflamed mucosa can reflect sustained remission and be a biomarker for monitoring therapeutic intensity in CD patients receiving anti-TNF agents.

Risk factors associated with high linezolid trough plasma concentrations

ABSTRACTAim: The major concern of linezolid is the adverse events. High linezolid trough serum concentration (Cmin) has been associated with toxicity. The aim of this study was to analyze factors associated with high Cmin.Methods: Main clinical characteristics of 104 patients treated with 600 mg/12 hours of linezolid were retrospectively reviewed. Samples were obtained just before the next dose after at least three doses and within the first 8 days of treatment. High Cmin was considered when it was >8 mg/L. Univariate and multivariate analysis were performed.Results: 34.6% patients had a Cmin >8 mg/L, and they were older and had more frequently an estimated glomerular filtration by MDRD <40 mL/min. There were more patients co-treated with rifampin in the group with low Cmin. The only factor independently associated with Cmin >8 was the renal function. Patients with an eGF < 40 mL/min had significantly higher Cmin than those with eGF > 80 mL/min (OR: 4.273) and there was a trend towards a high Cmin in patients with eGF between 40-80 mL/min (OR: 2.109).Conclusions: High Cmin were frequent, especially in patients with MDRD <40 mL/min. Therapeutic drug monitoring could be useful to avoid toxicity in patients with renal dysfunction.

Vancomycin dosing nomograms targeting high serum trough levels in different populations: pros and cons.

Utilization of higher doses of vancomycin to achieve the trough concentrations of 15-20mg/L for complicated infections has been recommended by the Infectious Diseases Society of America clinical practice guideline in recent years. Concerning this recommendation, several nomograms have been constructed targeting this optimal trough level range in different populations of patients. In this review, we have collected available nomograms targeting high trough serum levels of vancomycin, particularly comparing their advantages and limitations. The data were collected by searching Scopus, PubMed, Google scholar, Medline, and Cochrane database systematic reviews. The key words used as search terms were "vancomycin", "high trough level", "dosing nomogram", "dosing strategy", "neonates", "critically ill", "pediatrics", and "hemodialysis". We have included 17 related human studies published up to the date of this publication. Most of the available nomograms have determined the doses according to body weight and renal function. Their initial predicting success rate were 44-76% for non-critically ill patients, 42-84% for critically ill patients, 54% for one nomogram specially designed for hemodialysis patients, and 71% for the only nomogram developed for neonates. Based on validation studies, in most of cases, using a vancomycin dosing nomogram significantly improved and accelerated achievement of target trough concentrations. However, it should be noted that there are limited data about patients' clinical and microbiological outcomes and they are only validated in narrow groups of patients. Thus, their widespread application could not be encouraged for all patients before performing adequately powered, prospective randomized studies.

High vancomycin serum trough is not associated with reduction of mortality in methicillin-resistant Staphylococcus aureus bloodstream infections

High vancomycin serum trough is not associated with reduction of mortality in methicillin-resistant Staphylococcus aureus bloodstream infections

Vancomycin-induced nephrotoxicity with unusual high serum trough level in a critically ill young patient

Vancomycin-induced nephrotoxicity (VIN) occurs more commonly in the elderly, and the reported serum trough levels seldom exceed 80 mg/L. We present a case of VIN with serum trough levels exceeding 100 mg/L in a critically ill young patient with initially normal kidney function. The patient was admitted to the Intensive Care Unit after a motor vehicle accident. Vancomycin was initiated for methicillin-resistant Staphylococcus aureus infection localized in his cerebrospinal fluid. Vancomycin was administered for another 16 days, during which the serum trough levels remained below 10 mg/L, and the renal function tests were normal. After an increment in the vancomycin dose on day 17 from 750 mg every 6 h to 1 g every 6 h, the patient developed acute kidney injury during which his vancomycin trough level was 110.73 mg/L. The acute kidney injury resolved approximately 2 weeks after the discontinuation of vancomycin therapy. The present case highlights that critically ill patients on prolonged vancomycin therapy should be closely monitored, and dose increments should be made cautiously regardless of whether the patient is of young age or has low serum trough levels or normal renal function.

The association of elevated trough serum vancomycin concentrations with obesity.

Obese patients display differences in vancomycin drug disposition, which may complicate attainment of appropriate serum vancomycin concentrations (SVCs). This study was conducted to determine if obesity leads to trough SVCs above the therapeutic range. This retrospective cohort study sought to determine the rate and predictors of high (i.e. >20 mg/L) serum trough levels according to level of obesity. Increasing BMI predicted SVCs > 20 mg/L after controlling for dose, age, and serum creatinine. Obese patients had significantly higher mean trough SVCs compared to non-obese patients (16.5 mg/L vs 12.1 mg/L, p = 0.004) and a significantly higher proportion of obese patients had trough SVCs > 20 mg/L (18.9% vs 4.2%, p = 0.03). Increasing obesity predicted higher probabilities of SVCs > 20 mg/L. Development of alternative dosing and management strategies for vancomycin may be necessary to account for pharmacokinetic changes associated with obesity.

Adalimumab drug and antibody levels as predictors of clinical and laboratory response in patients with Crohn's disease

Adalimumab is an effective treatment for Crohn's disease (CD). Anti-adalimumab antibodies (AAA) and low trough serum drug concentrations have been implicated as pre-disposing factors for treatment failure. To assess adalimumab and AAA serum levels, and to examine their association and discriminatory ability with clinical response and serum C-reactive protein (CRP). We performed a cross-sectional study using trough sera from adalimumab-treated CD patients. Demographical data, Montreal classification, treatment regimen and clinical status were recorded. Serum adalimumab, AAA and CRP were measured. Receiver operating characteristic analysis and a multivariate regression model were performed to find drug and antibody thresholds for predicting disease activity at time of serum sampling. One hundred and eighteen trough serum samples were included from 71 patients. High adalimumab trough serum concentration was associated with disease remission (Area Under Curve 0.748, P < 0.001). A cut-off drug level of 5.85 μg/mL yielded optimal sensitivity, specificity and positive likelihood ratio for remission prediction (68%, 70.6% and 2.3, respectively). AAA were inversely related with adalimumab drug levels (Spearman's r = -0.411, P < 0.001) and when subdivided into categorical values, positively related with disease activity (P < 0.001). High drug levels and stricturing vs. penetrating or inflammatory phenotype, but not AAA levels, independently predicted disease remission in a multivariate logistic regression model. Adalimumab drug levels were inversely related to disease activity. High levels of anti-adalimumab antibodies were positively associated with disease activity, but this association was mediated mostly by adalimumab drug levels.

High versus low vancomycin serum trough regimen for Gram-positive infections: a meta-analysis

This study aimed to evaluate the impact of high vancomycin serum trough concentrations (≧15 mg/l) on clinical outcomes and nephrotoxicity among adult subjects. We searched MEDLINE, Cochrane Library, and CNKI systematically. A total of 17 studies were included. Meta-analysis found that high trough group showed no significant difference comparing to low trough group in treatment failure [relative risk (RR) 0·91, 95% confidence interval (CI) 0·67–1·24; P = 0·57] and all-cause mortality (RR 1·14, 95% CI 0·81–1·59; P = 0·46). However, the high trough concentrations were associated with lower treatment failure in bacteremia subgroup (RR 0·72, 95% CI 0·59–0·88; P = 0·001). High trough concentrations were associated with an increased risk of vancomycin-induced nephrotoxicity (RR 2·06, 95% CI 1·52–2·79; P<0·00001). Our meta-analysis indicates that high trough concentrations were not significantly superior to low trough concentrations in lowering treatment failure and mortality. Moreover, high trough concentrations significantly increased the risk of nephrotoxicity.

Low infliximab serum trough levels and anti-infliximab antibodies are prevalent in rheumatoid arthritis patients treated with infliximab in daily clinical practice: results of an observational cohort study

BackgroundTo get insight in the prevalence of high, or low/no serum infliximab trough levels in patients with low disease activity and if serum trough levels are stable and reliable longitudinally we conducted a prospective cohort studyMethodsIn a longitudinal, observational cohort of RA patients treated with infliximab for at least 6 months, treatment interval, DAS28, infliximab trough levels and anti-infliximab antibodies were assessed. Prevalence of low (<1 mg/l) and high (>5 mg/l) infliximab serum trough levels and anti-infliximab antibodies was recorded. Relationship of a change in anti-infliximab antibodies and treatment interval was described. Reliability of consecutive infliximab serum trough levels and anti-infliximab antibodies in patients with stable DAS28 and treatment was analysed with Spearman correlation and kappa-analysis.Results147 patients with a mean disease duration of 11 years (sd7) and DAS28 of 3.5 (sd1.3) at baseline were followed during 1.5 years. Inter-individual variability in infliximab levels in patients with low DAS28 was high (median 1.4 mg/L, IQR 3.35), with 31% (95%CI: 20-42%) having low (<1 mg/L) and 14% (95%CI 5–22) high trough levels (>5 mg/L). Interestingly also in RA patients with DAS28 ≤ 3.2, anti-infliximab antibodies were found in one-third of the patients, with half of them having antibodies every visit during a median of more than one year. Agreement for consecutive measurements of serum trough levels and anti-infliximab antibodies was high in stable patients: r = 0.97 (p = 0.00001) and kappa = 1.0 (SE 0.14) Anti-infliximab antibody appearance was influenced by interval increases (relative risk (RR) 5.2, 2.6-10.7), but patients still showed low infliximab levels.ConclusionsLow (and high) infliximab serum trough levels are prevalent, interestingly also in patients with low disease activity. Consecutive measurements of serum trough levels and anti-infliximab antibodies are reliable in stable patients. These test could be used to lower or stop infliximab in selected patients.

Pharmacokinetic approach for optimizing gentamicin use in neonates during the first week of life

Introduction:Gentamicin is an essential drug for the treatment of sepsis in neonates. The current work aims to optimize the use of gentamicin in neonates during the first week of life.Materials and Methods:The study was done at King Abdul-Aziz university hospital. Seventy-three neonates who received gentamicin 4-5 mg/kg and dosing interval at 24-48 hr were enrolled. Peak and trough serum levels of gentamicin were determined by immunoassay. Pharmacokinetic parameters were estimated assuming one compartment model and first order elimination kinetic. Analysis of variance was used to test the difference between means using Statistical Package for the Social Sciences (SPSS) Version 13.Results:About 73% of the patients attained peak gentamicin level within therapeutic range (6-12μg/ml), while 12% showed potentially toxic trough level (>2 μg /ml). The incidence of trough level was higher among patients receiving the drug every 24 hr. There was no clear correlation between high trough level and serum creatinine. High volume of distribution (Vd) of gentamicin (0.40-0.45) L/kg was observed. Neonates with proven sepsis showed higher mean Vd. Those with extremely low birth weight showed significantly longer half life of 11.5 h. Other neonates showed half life of (8-9) hr.Conclusions:Gentamicin dose of 4.5 mg/kg every 36 hr is recommended as simple empirical regimen during the 1st week of life for neonates with normal or LBW and every 48 hr for those with ELBW.

Controlled-release interferon alpha 2b, a new member of the interferon family for the treatment of chronic hepatitis C

Introduction: Combination therapy with pegylated interferon alpha (Peg-interferon) and ribavirin is currently the cornerstone of antiviral therapy for chronic hepatitis C. Monotherapy with Peg-interferon still is important for the treatment of chronic hepatitis B. With the advent of new therapies, protease inhibitors for chronic hepatitis C and nucleotide inhibitors for chronic hepatitis B, there remains a need for interferon-based therapies. The side effects of Peg-interferon are a main disadvantage and represent a stumbling block for many patients to enter and continue therapy.Areas covered: In this review, the authors will discuss controlled-release interferon alpha 2b (CR2b) (Locteron®, Biolex Therapeutics, Pittsboro, NC, USA), a new slow-release interferon alpha 2b preparation for the treatment of chronic viral hepatitis. Other alternative interferons will also be discussed.Expert opinion: CR2b is a slow-release microsphere preparation for the administration of plant-derived recombinant human interferon alpha 2b. Compared with Peg-interferon, treatment with CR2b shows less flu-like reactions and less depression, and is at least as effective as conventional Peg-interferon-based therapy in patients with chronic hepatitis C. CR2b has the added advantage of biweekly instead of once weekly administration. CR2b appears to cause more neutropenia than Peg-interferon alpha 2b. This may be due to higher trough serum levels of CR2b at the end of a dosing interval. The bone marrow effects of CR2b closely resemble those published for the registered Peg-interferon alpha 2a. CR2b appears to have at least comparable efficacy with fewer side effects than current registered Peg-interferons.

Gentamicin dosing in neonates: evaluation of a dosing protocol

Abstract A study was carried out to examine the dosing of gentamicin and to investigate some of the determinants of serum gentamicin concentrations in neonates at the Royal Hobart hospital, Tasmania, Australia, and to examine the appropriateness of the current dosing protocol (that of the Royal Children's hospital, Melbourne). Clinical and demographic data were retrospectively collected from the records of 39 neonates who had received therapy with gentamicin for suspected or proven septicaemia during the period May to September, 1993. Peak and trough serum concentrations of gentamicin were measured, at least 36 hours after starting therapy. The mean gestational age (± SD) of the sample was 32.3 ± 4.9 weeks, and 30 patients were male. The mean dosage of gentamicin was 4.0 ± 1.3mg/kg/day and the median duration of therapy was 4 days (range 2 to 22 days). Trough serum concentrations of gentamicin ranged from 0.6 to 6.0mg/L (mean 1.9 ± 1.0mg/L), with 35.9 per cent being 2.0mg/L or higher. Peak serum concentrations ranged from 4.3 to 12.9 mg/L (mean 6.1 ± 1.5 mg/L), with 89.7 per cent being between 5.0 and 8.0mg/L. The peak and trough serum concentrations were significantly related, while the total daily dosage of gentamicin and the resulting peak and trough serum concentrations were not significantly related. The trough serum concentration of gentamicin was significantly related to the serum creatinine concentration. Patients who had been dosed correctly according to the protocol were less likely to have a potentially toxic trough serum concentration of gentamicin. Those administered gentamicin every 12 hours tended to have higher serum trough concentrations of the drug than those who received it either 18- or 24-hourly. This study has confirmed that excessive serum concentrations of gentamicin occur frequently in neonates, a situation which may be improved by greater usage of an 18-hourly dosing regimen and prompt adjustment of dosage according to renal function.

Why Has Methicillin-Resistant Staphylococcus aureus Become Such a Successful Pathogen?

Methicillin-resistant Staphylococcus aureus infections affect previously healthy children and are associated with community rather than healthcare acquisition. However, some factors enhance risk including chronic skin conditions, obesity, a family member with skin or soft tissue infections, attendance at day care or participation in sports teams with contact (eg, wrestling, football, etc) and some ethnicities (eg, Native Americans/Pacific Islanders). Clinical presentation typically is a skin or soft tissue infection (∼85% of cases), but invasive infections such as septicemia, necrotizing pneumonia, and osteomyelitis; septic arthritis; pyomyositis; or combinations of these also occur. The predominant pathogen in the United States is a single clone of community-acquired methicillin-resistant Staphylococcus aureus, USA-300, but infections caused by USA-400 also occur. These infections require new strategies for diagnosis and an alteration in empiric treatment pending culture results. Culture and susceptibility testing is the cornerstone of accurate diagnosis and should be performed in all patients before specific therapy is initiated. If purulent material is available, it not only provides an appropriate specimen but also should be drained urgently. Every patient should be reassessed 48 hours after initial treatment. Empirical therapy for outpatient pediatric infections would include trimethoprim-sulfamethoxazole, clindamycin (if the isolate is susceptible or there is a low rate of resistance in the community), or doxycycline if the child is older than age 7 years. For serious infections, initial therapy would include vancomycin in a dose able to rapidly achieve high serum trough levels (≥15μg/mL) plus nafcillin. Specific therapy should be guided by results of susceptibility tests and duration by site(s) of infection.

Subcutaneous Administration of IgG in Primary Immune Deficiency Patients Results in Higher Trough Serum IgG Levels and Decreased Morbidity as Compared to IV Administration

Subcutaneous Administration of IgG in Primary Immune Deficiency Patients Results in Higher Trough Serum IgG Levels and Decreased Morbidity as Compared to IV Administration

Sustained effect after lowering high-dose infliximab in patients with rheumatoid arthritis: a prospective dose titration study

Objectives:In clinical trials only a small subset of patients with rheumatoid arthritis (RA) benefits from higher than standard dose of infliximab (>3 mg/kg/8 weeks). However, dose escalation of infliximab is...