Rate Of Therapeutic Failure Research Articles

Medical Therapies for Stricturing Crohn's Disease: Efficacy and Cross-Sectional Imaging Predictors of Therapeutic Failure.

Medical therapy efficacy remains controversial in stricturing Crohn's disease. Cross-sectional imaging, especially magnetic resonance imaging, has been suggested as very helpful to guide therapeutic decision making. To assess efficacy and predictors of therapeutic failure in patients receiving medical treatments for stricturing Crohn's disease. In this retrospective study, therapeutic failure was defined as symptomatic stricture leading to surgical or endoscopic therapeutics, hospitalization, treatment discontinuation or additional therapy and short-term clinical response as clinical improvement assessed by two physicians. The 55 cross-sectional imaging examinations (33 magnetic resonance imaging and 22 CT scan) before starting medical therapy were analyzed independently by two radiologists. Results were expressed as hazard ratio (HR) or odds ratio (OR) with 95% confidence intervals (95% CI). Among 84 patients, therapeutic failure rate within 60months was 66.6%. In multivariate analysis, Crohn's disease diagnosis after 40years old (HR 3.9, 95% CI [1.37-11.2], p=0.011), small stricture luminal diameter (HR 1.34, 95% CI [1.01-1.80], p=0.046), increased stricture wall thickness (HR 1.23, 95% CI [1.04-1.46], p=0.013) and fistula with abscess (HR 5.63, 95% CI [1.64-19.35], p=0.006) were associated with therapeutic failure, while anti-TNF combotherapy (HR 0.17, 95% CI [0.40-0.71], p=0.015) prevented it. Considering 108 therapeutic sequences, the short-term clinical response rate was 65.7%. In multivariate analysis, male gender (OR 0.15, 95% CI [0.03-0.64], p=0.011), fistula with abscess (OR 0.09, 95% CI [0.01-0.77], p=0.028) and comb sign (OR 0.23, 95% CI [0.005-0.97], p=0.047) were associated with short-term clinical failure. Anti-TNF combotherapy seemed to prevent therapeutic failure, and cross-sectional imaging should be systematically performed to help medical management in stricturing Crohn's disease.

Comparison of oral antibiotic failure rates in post-Roux-en-Y gastric bypass patients versus controls

BackgroundDue to the malabsorptive nature of the Roux-en-Y gastric bypass (RYGB), there is a potential for impaired absorption of oral medications. Clinical outcomes of patients who receive oral antibiotics after RYGB have not been adequately described in the literature. ObjectivesThe primary objective was composite therapeutic failure. Secondary objectives included comparing failure rates between antibiotic classes and at various time points since RYGB. SettingUniversity hospital, United States. MethodsPatients with a history of RYGB and controls who received an eligible oral antibiotic for urinary tract infection, skin and soft tissue infection, or community acquired pneumonia between April 1, 2008, and September 30, 2015, were included via retrospective chart review. Therapeutic failure rates between groups were compared and adjusted for body mass index and infection type. Failure rates among antibiotic classes and various time points since RYGB (0–1 yr, 1–1.9 yr, and≥2 yr) were also compared. ResultsA total of 58 RYGB and 128 controls met inclusion and exclusion criteria. Composite therapeutic failure occurred in the RYGB and control group in 14 (24.1%) and 20 patients (15.6%), respectively (P = .18; odds ratio, 1.8; 95% confidence interval .8–4.4). RYGB patients who received fluoroquinolones or sulfonamides had a significantly increased risk of therapeutic failure. ConclusionsRYGB was not associated with a statistically significant increased risk of composite therapeutic failure of oral antibiotics in the treatment of urinary tract infection, skin and soft tissue infection, or community acquired pneumonia compared with patients with no history of gastrointestinal resection. Further research is warranted to understand clinical outcomes of RYGB patients who receive oral antibiotics.

Terapia de Aceptación y Compromiso como Tratamiento de Elección para el TOC: un Estudio de Caso

El trastorno obsesivo-compulsivo (TOC) es uno de los trastornos psiquiátricos con mayor resistencia a los tratamientos y que mayor sufrimiento causa. Por ello, se recomienda la opción combinada farmacológica y psicoterapéutica, en su abordaje. Sin embargo, estos tratamientos de elección aún mantienen tasas significativas de fracaso terapéutico. En este estudio se pretende analizar el efecto de un tratamiento basado en terapia de aceptación y compromiso (ACT), sobre la sintomatología del TOC y la satisfacción con las direcciones valiosas. Para ello, se presenta un estudio de un caso clínico con TOC. Se aplicó un tratamiento basado en ACT en 18 sesiones de terapia individual. Como resultados, se observaron reducciones en psicopatología propia del trastorno, ansiedad y sintomatología depresiva; se suprimió el tratamiento farmacológico; asimismo, se encontraron niveles mayores de satisfacción con respecto a sus direcciones valiosas. En conclusión, este estudio apunta a la aplicabilidad de la ACT como tratamiento de elección para el trastorno obsesivo-compulsivo.

Endoscopic ultrasound-guided biliary access versus precut papillotomy in patients with failed biliary cannulation: a retrospective study.

Background and aims Precut papillotomy is widely used after failed biliary cannulation. Endoscopic ultrasound (EUS)-guided biliary access techniques are newer methods to facilitate access and therapy in failed cannulation. We evaluated the impact of EUS-guided biliary access on endoscopic retrograde cholangiopancreatography (ERCP) success and compared these techniques to precut papillotomy. Patients and methods We retrospectively compared two ERCP cohorts. One cohort consisted of biliary ERCPs (n = 1053) attempted in patients with native papillae and surgically unaltered anatomy in whom precut papillotomy and/or EUS-guided biliary access were routinely performed immediately after failed cannulation. This cohort was compared with a similar ERCP cohort (n = 1062) in which only precut papillotomy was available for failed cannulation. The following outcomes were compared: conventional cannulation success, rates of attempted advanced access techniques (precut or EUS), precut success, EUS-guided biliary access success, and ERCP failure rates. Results Although conventional cannulation success, rates of attempted advanced access technique (precut or EUS), and precut success were similar, the ERCP failure rate was lower when both EUS-guided biliary access and precut were available (1.0 % [95 % confidence interval (CI) 0.4 - 1.6]), compared with when only precut was possible for failed access (3.6 % [95 %CI 2.5 - 4.7]; P < 0.001). Success for EUS-guided biliary access (95.1 % [95 %CI 89.7 - 100]) was significantly higher than for precut (75.3 % [95 %CI 68.2 - 82.4]; P < 0.001), and mainly due to superiority in malignant obstruction (93.5 % vs. 64 %; P < 0.001). Conclusions EUS-guided biliary access decreases the rate of therapeutic biliary ERCP failure. Our results support the use of EUS-guided biliary access to optimize single-session ERCP success. In experienced hands, these techniques appear as effective, if not more so, than precut papillotomy.

Adiponectin, Insulin Sensitivity, β-Cell Function, and Racial/Ethnic Disparity in Treatment Failure Rates in TODAY.

The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study demonstrated that glycemic failure rates in the three treatments combined-metformin plus rosiglitazone, metformin alone, and metformin plus lifestyle-were higher in non-Hispanic blacks (NHB; 52.8%) versus non-Hispanic whites (NHW; 36.6%) and Hispanics (H; 45.0%). Moreover, metformin alone was less effective in NHB versus NHW versus H youth. This study describes treatment-associated changes in adiponectin, insulin sensitivity, and β-cell function over time among the three racial/ethnic groups to understand potential mechanism(s) responsible for this racial/ethnic disparity. TODAY participants underwent periodic oral glucose tolerance tests to determine insulin sensitivity, C-peptide index, and oral disposition index (oDI), with measurements of total and high-molecular-weight adiponectin (HMWA). At baseline NHB had significantly lower HMWA than NHW and H and exhibited a significantly smaller increase (17.3% vs. 33.7% vs. 29.9%, respectively) during the first 6 months overall. Increases in HMWA were associated with reductions in glycemic failure in the three racial/ethnic groups combined (hazard ratio 0.61, P < 0.0001) and in each race/ethnicity separately. Over time, HMWA was significantly lower in those who failed versus did not fail treatment, irrespective of race/ethnicity. There were no differences in treatment-associated temporal changes in insulin sensitivity, C-peptide index, and oDI among the three racial/ethnic groups. HMWA is a reliable biomarker of treatment response in youth with type 2 diabetes. The diminutive treatment-associated increase in HMWA in NHB (∼50% lower) compared with NHW and H may explain the observed racial/ethnic disparity with higher therapeutic failure rates in NHB in TODAY.

Prediction of Relapse After Cognitive-Behavioral Treatment of Gambling Disorder in Individuals With Chronic Schizophrenia: A Survival Analysis

Gambling disorder (GD) in individuals with chronic schizophrenia is relevant because there are higher rates of GD in schizophrenic populations (10%) than in the nonschizophrenic population (1%–5%). In addition, these patients have more severe alcohol use disorder (i.e., meeting at least 6 of the DSM-5 11 criteria for diagnosis of this disorder), higher depression scores, a poor adherence to treatment, and more frequent use of outpatient mental health care. One of the main problems in GD is therapeutic failure (defined as three or more lapse episodes during treatment) or relapse (three or more lapse episodes in the follow-up period). Predicting a relapse of GD in individuals with chronic schizophrenia can be useful in targeting the patients for aftercare services. The main aim of this study was to estimate the time to a GD relapse (survival rate) and to evaluate some of the qualitative and quantitative variables related to a GD relapse by a survival analysis. The sample consisted of 35 patients with chronic schizophrenia and GD who were treated with pharmacological and cognitive-behavioral therapy. The therapeutic failure rate in the treatment period was 43%, and it was associated with the number of episodes of schizophrenia, the age of gambling onset, and the age of the patients. The relapse rate in the follow-up period was 32%, and it was associated with the patients’ age, educational level, and weekly allowance. The implications of this study for future research are discussed.

Clinical and Diagnostic Aspects of Brucellosis and Antimicrobial Susceptibility of Brucella Isolates in Hamedan, Iran.

Current drug regimens for brucellosis are associated with relatively high rates of therapeutic failure or relapse. Reduced antimicrobial susceptibility of Brucella spp. has been proposed recently as a potential cause of therapeutic failure. The aim of this study was to evaluate the antibiotic resistance pattern of Brucella melitensis clinical isolates by E-test method in Hamadan, west of Iran. In a 15-month period, all patients with suspected brucellosis were enrolled. Blood specimens were collected for diagnosis of brucellosis by BACTEC system and serological tests. Antimicrobial susceptibility of clinical isolates to 7 antibiotics was assessed by the E-test method. One hundred forty-nine patients with brucellosis were evaluated. 38.3% of cultures of clinical samples were positive for BACTEC system, of which 91.2% were associated with a positive serological test result. No significant associations were found between serology and the culture method. All Brucella isolates were susceptible to doxycycline, streptomycin, gentamicin, ciprofloxacin, and moxifloxacin. However, decreased sensitivity to rifampin and trimethoprim-sulfamethoxazole was found in 35.1% and 3.5% of isolates, respectively. Because of the high rates of intermediate sensitivity to rifampin among Brucella isolates, this drug should be prescribed with caution. We recommend restricting the use of rifampin for treatment of brucellosis except as an alternative drug for special situations.

Evaluation of the paediatric dose of chloroquine in the treatment of Plasmodium vivax malaria.

BackgroundChloroquine (CQ) continues to be the first-line medication used worldwide in the treatment of Plasmodium vivax malaria. The dose recommended by the World Health Organization is 25 mg/kg independently of the age of the subject. Nonetheless, the pharmacokinetics and pharmacodynamics of drugs in children are different from those in adults and may influence the drug concentrations in blood and become risk factors for therapeutic failure and/o resistance to CQ.MethodsThis study is a secondary analysis of the data from a clinical trial in which children over 5 years of age were administered 25 mg/kg of CQ, and CQ concentrations in blood were measured at day 7 of follow-up. Models of regression and comparison were used to evaluate and compare the CQ dose taken per kg/body weight, the CQ dose calculated based on body surface area, CQ levels in blood on day 7 and the age of the population.ResultsThe younger the study population the greater the difference between the dose per kg/body weight (real dose) and that calculated according to the BSA (theoretical dose). The difference between the two doses was −181.206 mg in the 5–9 years of age group (CI 95 % −195.39; −167.02 mg) and −71.39 mg (CI 95 % −118.61; −23.99 mg) in the 10–14-year-old group. The CQ concentrations in blood on day 7 differed in patients over and under 15 years (p = 0.008). A negative correlation was found between the real and theoretical dose (difference in dose) and the age in years (R2 = 0.529, p = 0.001). A negative correlation was also found between the difference in dose (mg) and CQ concentrations on day 7 (ng/ml) (r = −0.337, p = 0.001). Children under 15 years were found to have a higher rate of therapeutic failure than those over 15 (28 vs 4.2 %, respectively) (Kaplan–Meier p = 0.005).ConclusionsA CQ dose of 25 mg/kg for the treatment of P. vivax malaria may be too low in children as demonstrated by the reduction in CQ concentrations in blood at day 7 of follow-up. This under-dosage is probably associated with the higher rate of therapeutic failure found in children under 15 years (28 vs 4.3 %). These results suggest the need to review the paediatric doses of CQ currently used.

Evaluation of cephalexin failure rates in morbidly obese patients with cellulitis.

Identification of adequate antimicrobial dosing regimens for morbidly obese patients is essential given the simultaneous increase in morbid obesity and cellulitis prevalence in recent years. Insufficient data currently exist to describe the effectiveness of extrapolating traditional antibiotic dosing strategies to morbidly obese patients with cellulitis. The primary objective of this study was to compare therapeutic failure rates in non-obese and morbidly obese patients with cellulitis when treated with cephalexin at standard dosing. This was a single-centre, retrospective cohort analysis. Adult patients hospitalized or under inpatient observation at a 1265-bed academic medical centre who received cephalexin monotherapy for non-purulent cellulitis from 2005 to 2015 were evaluated for inclusion. Patients were divided into two cohorts based on body mass index (BMI), where BMI <30kg/m(2) was defined as non-obese and BMI ≥40kg/m(2) as morbidly obese. Patients with critical risk factors for purulent or polymicrobial cellulitis were excluded. The primary outcome, therapeutic failure, was defined as a need for extended or additional antimicrobial therapy, surgical intervention, emergency department visit, or re-hospitalization within two to thirty days after cephalexin initiation. A total of 94 patients (69 non-obese and 25 morbidly obese) met inclusion and exclusion criteria, which was below the estimated sample size needed to reach desired power. The rate of therapeutic failure in the morbidly obese group was similar to the non-obese group (20% vs. 14·5%, P=0·53). Patients most commonly had extended or additional antibiotics prescribed in response to therapeutic failure with cephalexin. Cephalexin failure rates for cellulitis did not differ statistically between morbidly obese and non-obese patients. The underpowered nature of this study is a limitation. Until further study with a larger sample size is completed, empiric adjustment of cephalexin dosing based solely on BMI may not be necessary.

Factors involved in continuance of atazanavir-based regimens: Results from a cohort of HIV1-positive patients

We evaluated predictive factors involved in durability and therapeutic failure of atazanavir (ATV)-based antiretroviral regimens with or without ritonavir (r) in real life setting. This retrospective study of HIV-1-positive patients evaluated the factors related to ATV continuance and the time-dependent probability of therapeutic failure (HIV-RNA >200 copies/mL and concomitant discontinuation of ATV). We also investigated the rate of therapeutic failure and the variations in total bilirubin levels from starting unboosted ATV-based regimens. The study involved 1030 patients: 183 treatment-naïve patients (17.8%) started ATV/r (17 subsequently switched to unboosted ATV); 653 (63.4%) switched to ATV/r from previous antiretroviral regimens (121 subsequently switched to unboosted ATV); and 194 (18.8%) switched to unboosted ATV from previous ATV-free regimens. The median ATV follow-up was 28 months (interquartile range 7–56). The risk of ATV discontinuation was significantly lower in patients switched to unboosted ATV from ATV/r (HR 0.45; p < 0.0001). The discontinuation of ATV correlated with female gender (HR 1.26; p = 0.035), use of a zidovudine/didanosine/stavudine containing backbone (HR 1.8; p = 0.004), and a baseline CD4+ cell counts of <200/μL (HR 1.54; p = 0.003), the last of which was also associated with a higher risk of therapeutic failure (HR 2.42; p = 0.001). Total bilirubin levels were significantly lower in the patients switching from ATV/r to unboosted ATV. Unboosted ATV-based therapies are safe and effective options in patients whose immuno-virological conditions are stable, and allow the long-term survival of ATV-containing regimeans.

Treatment of chronic hepatitis C with direct-acting antivirals: The role of resistance.

The use of direct-acting antivirals (DAAs) to treat chronic hepatitis C has resulted in a significant increase in rates of sustained viral response (around 90%-95%) as compared with the standard treatment of peginterferon/ribavirin. Despite this, however, the rates of therapeutic failure in daily clinical practice range from 10%-15%. Most of these cases are due to the presence of resistant viral variants, resulting from mutations produced by substitutions of amino acids in the viral target protein that reduce viral sensitivity to DAAs, thus limiting the efficacy of these drugs. The high genetic diversity of hepatitis C virus has resulted in the existence of resistance-associated variants (RAVs), sometimes even before starting treatment with DAAs, though generally at low levels. These pre-existing RAVs do not appear to impact on the sustained viral response, whereas those that appear after DAA therapy could well be determinant in virological failure with future treatments. As well as the presence of RAVs, virological failure to treatment with DAAs is generally associated with other factors related with a poor response, such as the degree of fibrosis, the response to previous therapy, the viral load or the viral genotype. Nonetheless, viral breakthrough and relapse can still occur in the absence of detectable RAVs and after the use of highly effective DAAs, so that the true clinical impact of the presence of RAVs in therapeutic failure remains to be determined.

Routinely Established Skewed Thiopurine Metabolism Leads to a Strikingly High Rate of Early Therapeutic Failure in Patients With Inflammatory Bowel Disease.

The conventional thiopurines azathioprine and mercaptopurine are considered maintenance immunosuppressive drugs of choice in the treatment of inflammatory bowel disease (IBD). Unfortunately, treatment is often discontinued because of adverse events (AEs) or refractoriness, retrospectively associated with the high levels of the thiopurine metabolites 6-methylmercaptopurine ribonucleotides (6-MMPR). Patients with a clinically "skewed" thiopurine metabolism may be particularly at risk for therapy failure. We determined the predictive value of this pharmacological phenomenon in patients with IBD during regular thiopurine therapy. Clinical effectiveness and tolerability of weight-based thiopurine therapy were determined in all patients with IBD displaying a skewed metabolism [ratio 6-MMPR/6-thioguanine nucleotide (6-TGN) >20]. All samples were routinely assessed between 2008 and 2012, as part of standard clinical follow-up after initiation of conventional thiopurine therapy. Forty-one (84%) of 49 included patients with IBD discontinued thiopurines (55% female, 53% with Crohn disease) with a median duration of 14 weeks (range, 7-155). The majority of patients with a skewed metabolism discontinued thiopurines because of adverse events (55%) or refractoriness (12%). The most commonly observed adverse event was hepatotoxicity (18 patients, 37%). Median 6-TGN level was 159 pmol/8 × 10 RBC (range, 46-419), median 6-MMPR level was 11,020 pmol/8 × 10 RBC (range, 3610-43,670), and the median 6-MMPR/6-TGN ratio was 72 (range, 29-367). Thiopurine therapy failure was associated with a ratio above 50 (P < 0.03). Hepatotoxicity occurred more frequently in patients with an extremely skewed metabolism (6-MMPR/6-TGN ratio >100) (P < 0.01). This study demonstrates that a routinely established skewed metabolism is a major risk factor for future thiopurine failure in patients with IBD. These observations imply that routine thiopurine metabolite measurements may be used as a prognostic tool to identify those patients with an aberrant-skewed metabolism at an early stage, possibly benefitting from therapy adjustments.

Hookworm infection among patients with pulmonary tuberculosis: Impact of co-infection on the therapeutic failure of pulmonary tuberculosis

Objective/backgroundThe aim of this study is to determine the rate of hookworm infection among patients with pulmonary tuberculosis (TB) and to find out if there is a relation between hookworm infection and the therapeutic failure of pulmonary TB. MethodsWe carried out a prospective, hospital-based study. The study included 231 naïve patients with pulmonary TB, consecutively. Patients were evaluated at the 4th month of therapy for persistence of Mycobacterium tuberculosis infection. All patients had clinical evaluation, laboratory investigations (including sputum culture and stool microscopic examination), and imaging studies (abdominal ultrasonography and chest radiography). ResultsThe study population mean age was 42.7±13.9years old with 26.8% of them 40years old or more. Out of 231 patients, 133 (57.6%) were men. Therapeutic failure rate of pulmonary TB was 29.4%. Hookworm infection was diagnosed among 16.5% of patients and 27.7% had diabetes mellitus (DM). Using multivariate analysis, it was found that age of 40years or more (odds ratio [OR] 8.4; 95% confidence interval [CI] 1.7–41.3; p=.009), hookworm infection (OR 7.6; 95% CI 1.2–49.9; p=.034), and DM (OR 5.9; 1.2–28; p=.027) were independently associated with therapeutic failure of pulmonary TB among the study population with pulmonary TB. ConclusionIn conclusion, the rate of therapeutic failure of pulmonary TB is high. Besides older age and DM, hookworm infection can reduce the therapeutic response of pulmonary TB. Screening for and control of DM and hookworm infection among patients with pulmonary TB may improve their therapeutic response.

The changing face of diabetes in youth: lessons learned from studies of type 2 diabetes

The incidence of youth type 2 diabetes (T2D), linked with obesity and declining physical activity in high-risk populations, is increasing. Recent multicenter studies have led to a number of advances in our understanding of the epidemiology, pathophysiology, diagnosis, treatment, and complications of this disease. As in adult T2D, youth T2D is associated with insulin resistance, together with progressive deterioration in β cell function and relative insulin deficiency in the absence of diabetes-related immune markers. In contrast to adult T2D, the decline in β cell function in youth T2D is three- to fourfold faster, and therapeutic failure rates are significantly higher in youth than in adults. Whether the more aggressive nature of youth T2D is driven by genetic heterogeneity or physiology/metabolic maladaptation is yet unknown. Besides metformin, the lack of approved pharmacotherapeutic agents for youth T2D that target the pathophysiological mechanisms is a major barrier to optimal diabetes management. There is a significant need for effective therapeutic options, in addition to increased prevention, to halt the projected fourfold increase in youth T2D by 2050 and the consequences of heightened diabetes-related morbidity and mortality at younger ages.

Hydrodistension with or without fulguration of hunner lesions for interstitial cystitis: Long-term outcomes and prognostic predictors.

Hydrodistension of the bladder, with optional fulguration of Hunner lesions, is one of the recommended therapies for interstitial cystitis (IC). The aims of this study are to evaluate long-term outcomes of hydrodistension and identify outcome predictors. The study cohort was 191 newly diagnosed IC patients (155 women and 36 men) who underwent hydrodistension with fulguration of Hunner lesions if detected between 2007 and 2013 at our institution. The primary outcome was therapeutic failure, which was defined as repeat hydrodistension, bladder instillation therapy, or narcotic use for pain control. Clinical features, including comorbidities and endoscopic findings, were analyzed along with the outcome. The cohort comprised 126 patients of Hunner type IC and 65 patients of non-Hunner type IC. The mean time to therapeutic failure was 28.5 months in Hunner type IC and 25.2 months in non-Hunner type IC. The therapeutic failure rate was higher in non-Hunner type IC at 17.3 months; however, the long-term outcomes reversed thereafter. The mean time to therapeutic failure was shorter in patients with lumbar spinal stenosis (LSS) or irritable bowel syndrome (IBS). Multivariate analysis identified LSS as a predictor for failure in Hunner type IC and non-Hunner type IC (HR = 18.8, P = 0.001; HR = 3.8, P = 0.028, respectively) and IBS in non-Hunner type IC (HR = 18.0, P = 0.008). Bladder hydrodistension, with fulguration of the Hunner lesions, improved IC symptoms. The outcome was worse in non-Hunner type IC shortly after hydrodistension but eventually comparable across the two types. Concomitant LSS and IBS were predictors for poor outcome. Neurourol. Urodynam. 35:965-969, 2016. © 2015 Wiley Periodicals, Inc.

Accessory Gene Regulator Polymorphism and Vancomycin Minimum Inhibitory Concentration in Methicillin-Resistant Staphylococcus aureus.

BackgroundMethicillin-resistant Staphylococcus aureus (MRSA) bacteremia with a vancomycin minimum inhibitory concentration (MIC) of 2 µg/mL presents a high rate of therapeutic failure in response to vancomycin. In addition, polymorphism in accessory gene regulator (agr) is associated with vancomycin therapeutic effects. The association between agr polymorphism and vancomycin MICs was investigated in MRSA isolates.MethodsAgr group-specific PCR was conducted on 118 MRSA bloodstream isolates. Vancomycin susceptibility tests were conducted, while E-test GRD (bioMérieux SA, France) was used to detect heterogeneous vancomycin-intermediate S. aureus (hVISA).ResultsOf the 118 MRSA isolates, 59 (50.0%), 43 (36.4%), and 10 (8.5%) isolates belonged to agr group I, II, and III, respectively. Six isolates could not be classified. Twenty-six, 73, and 19 isolates presented a vancomycin MIC of 2, 1, and 0.5 µg/mL, respectively. Nine (34.6%), 14 (53.8%), and 2 (7.7%) isolates with MICs of 2 µg/mL belonged to agr group I, II, and III, respectively. Thirty-seven (50.6%), 26 (35.6%), and 6 (8.2%) isolates with MICs of 1 µg/mL belonged to agr group I, II, and III, respectively. Thirteen (68.4%), 3 (15.8%), and 2 (10.5%) isolates with MICs of 0.5 µg/mL belonged to agr group I, II, and III, respectively. The agr group II presented more isolates with MIC of 2 µg/mL (32.6%) than the agr non-group II (16%). Four isolates tested positive for hVISA. Three of them belonged to agr group II.ConclusionsMRSA isolates with vancomycin MIC of 2 µg/mL were more common in agr group II than in agr non-group II.

Factors associated with the failure of arthroscopic surgery treatment in patients with femoroacetabular impingement: A cohort study

ObjectiveThe aim of this study was to evaluate the association of the anatomical and functional characteristics with therapeutic failure in patients with femoroacetabular impingement, who underwent hip arthroscopy. Materials and methodsA cohort study was performed on 179 patients with femoroacetabular impingement who underwent hip arthroscopy between 2004 and 2012. The demographic, anatomical, functional, and clinical information were recorded. A logistic regression model and ANCOVA were used in order to compare the described characteristics with the treatment outcomes of the hip arthroscopy. ResultsThe median time of follow-up for symptoms was 13 months (8–30), and the mean time of follow-up after surgery was 23.83±9.8 months. At the end of the follow-up 3.91% of the patients were considered as a therapeutic failure. The WOMAC score in pain and functional branches, as well as the total WOMAC score, showed significant differences (p<0.05). The mean WOMAC score was higher (0–100 with 0 being a perfect score) in the group of patients who failed after surgery as compared with the group who meet the requirements for a successful treatment, 65.9 vs 48.8, respectively (mean difference 17.0; 95% CI; 1.3–32.6; p=0.033). ConclusionThe poor functional state prior to arthroscopic treatment of femoroacetabular impingement, mainly due to preoperative pain, assessed using the WOMAC scale, is associated with a higher therapeutic failure rate.

Effect of initial empiric antibiotic therapy combined with control of the infection focus on the prognosis of patients with secondary peritonitis.

In patients with intra-abdominal infection, inappropriate initial empiric antibiotic therapy is associated with greater morbidity. We evaluated the impact of adequate empiric antibiotic treatment together with control of the infection focus on the morbidity and mortality rates of patients with secondary peritonitis. This was a prospective, observational study with the participation of 24 Spanish hospitals and 362 patients with secondary peritonitis (262 community-acquired, 100 post-operative). Therapeutic failure (infectious complications or death) was classified into four categories according to whether empiric antibiotic treatment was appropriate and the infection focus was controlled. The rates of therapeutic failure, re-operation, and mortality were 48%, 13%, and 8%, respectively. Empiric antibiotic treatment was inappropriate in 39% of cases, which was associated with a higher rate of surgical site infection (53% vs. 40%; p=0.031) and death (12% vs. 5%; p=0.021) than was observed in patients receiving appropriate initial empiric therapy. Eight percent of patients in whom control of the infection focus was not obtained suffered from more infectious complications (76% vs. 52%; p=0.01) and surgical site infections (69% vs. 44%; p=0.01); and in this group, both therapeutic failure and mortality rates were similar, independent of whether the empiric antibiotic therapy was appropriate. Inappropriate initial empiric antibiotic therapy was associated with higher rates of therapeutic failure, surgical site infection, re-operation, and death. Classification of therapeutic failure into four categories according to the appropriateness of empiric antibiotic therapy and the success of infection control provided excellent discrimination of morbidity and death.

Vancomycin revisited - 60 years later.

Vancomycin is one of the older antibiotics that has been now in clinical use close to 60 years. Earlier on, vancomycin was associated with many side effects including vestibular and renal, most likely due to impurities contained in early vancomycin lots. Over the years, the impurities have been removed and the compound has now far less vestibular adverse effects, but still possesses renal toxicity if administered at higher doses rendering trough serum levels of >15 mcg/mL or if administered for prolonged periods of time. Vancomycin is effective against most Gram-positive cocci and bacilli with the exception of rare organisms as well as enterococci that became vancomycin resistant, mostly Enterococcus faecium. The major use of vancomycin today is for infections caused by methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE) and amoxicillin-resistant enterococci. In its oral form, vancomycin is used to treat diarrhea caused by Clsotridium difficile. With S. aureus, there are only a handful of vancomycin-resistant strains. Nevertheless, a “vancomycin creep” that is slow upward trending of vancomycin MIC from <1 mcg/mL to higher values has been noted in several parts of the world, but not globally, and strains that have MIC’s of 1.5–2 mcg/mL are associated with high therapeutic failure rates. This phenomenon has also been recently recognized in methicillin-susceptible S. aureus (MSSA). While vancomycin is relatively a safe agent adverse events include the “red man” syndrome, allergic reactions, and various bone marrow effects as well as nephrotoxicity. Vancomycin has been a very important tool in our therapeutic armamentarium that remained effective for many years, it is likely remain effective as long as resistance to vancomycin remains controlled.

Factores asociados al fracaso terapéutico de la cirugía artroscópica en pacientes con choque femoroacetabular: un estudio de cohorte

ObjectiveThe aim of this study was to evaluate the association of the anatomical and functional characteristics with therapeutic failure in patients with femoroacetabular impingement, who underwent hip arthroscopy. Materials and methodsA cohort study was performed on 179 patients with femoroacetabular impingement who underwent hip arthroscopy between 2004 and 2012. The demographic, anatomical, functional, and clinical information were recorded. A logistic regression model and ANCOVA were used in order to compare the described characteristics with the treatment outcomes of the hip arthroscopy. ResultsThe median time of follow-up for symptoms was 13 months (8-30), and the mean time of follow-up after surgery was 23.83±9.8 months. At the end of the follow-up 3.91% of the patients were considered as a therapeutic failure. The WOMAC score in pain and functional branches, as well as the total WOMAC score, showed significant differences (P<.05). The mean WOMAC score was higher (0 to 100 with 0 being a perfect score) in the group of patients who failed after surgery as compared with the group who meet the requirements for a successful treatment, 65.9 vs 48.8, respectively (mean difference 17.0; 95% CI; 1.3-32.6; P=.033). ConclusionThe poor functional state prior to arthroscopic treatment of femoroacetabular impingement, mainly due to preoperative pain, assessed using the WOMAC scale, is associated with a higher therapeutic failure rate.