Mar 222014
 
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Biological Therapies in Rheumatoid Arthritis and the Risk of Opportunistic Infections: A meta-analysis.

Clin Infect Dis. 2014 Mar 18;

Authors: Kourbeti IS, Ziakas PD, Mylonakis E

Abstract
Objective. Biologic agents are increasingly used to treat patients with rheumatoid arthritis. We aimed to review their association with opportunistic infections (OIs), including fungal, viral (with a focus on herpes virus-related infections), tuberculosis and other mycobacterial infections. Methods. We searched PubMed and EMBASE up to June 2013 and complemented the search with the reference lists of eligible articles. Randomized trials on rheumatoid arthritis that compared any approved biologic agent with controls and reported the risk of opportunistic infections were included in the analysis. Results. Seventy trials that included 32,504 patients (21,916 patients on biologics and 10,588 on placebo) were deemed eligible. Biologic agents increased the risk of opportunistic infections (pooled Peto odds ratio, 1.79; 95% CI, 1.17-2.74; I(2)=3%), resulting in 1.7 excess infections per 1,000 patients treated (number needed to harm, NNH=582). A significant risk was noted for mycobacterial (OR, 3.73; 95% CI, 1.72-8.13; I(2)=0), and viral (OR, 1.91; 95% CI, 1.02-3.58;I(2)=0) infections. Interestingly, no significant differences were found for invasive and superficial fungal infections (OR, 1.31; 95% CI, 0.46-3.72), invasive fungal infections (OR, 2.85; 95% CI, 0.68-11.91), Pneumocystis jirovecii pneumonia (OR, 1.77; 95% CI 0.42-7.47), varicella-zoster virus (OR, 1.51; 95% CI 0.71-3.22), as well as overall attributed mortality to OIs (OR, 1.91; 95% CI, 0.29-12.64). Conclusions. Among rheumatoid arthritis patients, biologic agents are associated with a small but significant risk of specific opportunistic infections. This increase is associated with mycobacterial diseases and does not appear to impact overall mortality. Because OIs are a relatively rare complication of biological agents, large registries are needed in order to identify the exact impact in different OIs and to compare the different biological agents.

PMID: 24647016 [PubMed - as supplied by publisher]

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Mar 202014
 
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The Efficacy of Daptomycin vs. Vancomycin for MRSA Bloodstream Infection in Patients with Impaired Renal Function.

Clin Infect Dis. 2014 Mar 18;

Authors: Weston A, Golan Y, Holcroft C, Snydman DR

Abstract
Background. Concerns regarding the efficacy of daptomycin for Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections in patients with impaired renal function are reflected in a recent package insert change by the FDA. However, this decision was based on a small subgroup analysis and it is unclear if this is a true association. Methods. We conducted a retrospective cohort study of patients with MRSA bacteremia treated at a tertiary hospital from 2001-2011 and who received either vancomycin or daptomycin. We used propensity score and multivariable logistic regression to assess the outcome of treatment failure, via blinded adjudication, in daptomycin vs. vancomycin treated subjects and the interaction with renal function. Results. There were 150 patients analyzed, 100 in the Vancomycin arm and 50 in the Daptomycin arm. The average age was 61 and 60% were men. Of patients treated with daptomycin or vancomycin, 29 (58%) and 51 (51%), respectively, had a GFR <50 ml/min/1.73 m(2). Compared to vancomycin, neither the usage of daptomycin in patients with a GFR>50 ml/min/1.73 m(2) (OR 0.45, 95% CI 0.11-1.79) nor in patients with a GFR of <50 ml/min/1.73 m(2) (OR 0.46, 95% CI 0.11-1.94) was significantly associated with treatment failure. There was no significant interaction between them (p=0.54). Conclusions. In patients with MRSA bacteremia, daptomycin efficacy was not affected by GFR level and was similar to vancomycin's efficacy. Although our sample size was small, it was larger than than the one used by the FDA. However, smaller differences may be significant with a larger sample size.

PMID: 24642554 [PubMed - as supplied by publisher]

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Mar 192014
 
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The common occurrence of ceftriaxone-resistant methicillin sensitive Staphylococcus aureus at a community teaching hospital.

Clin Infect Dis. 2014 Mar 14;

Authors: Pickering A, Hariri R, Harrison LH, Marsh JW, Tasneem A, Freedy H, Wilson L, Bonilla H

Abstract
Although the rate of ceftriaxone resistance in methicillin-sensitive Staphylococcus aureus (MSSA) is reported at approximately 3% in the literature, findings at our institution suggest it is grossly underestimated. Eighty-seven percent of MSSA isolates tested were non-suceptible to ceftriaxone and activity of this antibiotic could not be predicted using other beta-lactams.

PMID: 24633690 [PubMed - as supplied by publisher]

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Mar 102014
 
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NAP1 Strain Type Predicts Outcomes from Clostridium difficile Infection.

Clin Infect Dis. 2014 Mar 5;

Authors: See I, Mu Y, Cohen J, Beldavs ZG, Winston LG, Dumyati G, Holzbauer S, Dunn J, Farley MM, Lyons C, Johnston H, Phipps E, Perlmutter R, Anderson L, Gerding DN, Lessa FC

Abstract
Background. Studies conflict regarding the importance of the fluoroquinolone-resistant North American pulsed-field gel electrophoresis type 1 (NAP1) strain in Clostridium difficile infection (CDI) outcome. We describe strain types causing CDI and evaluate their association with patient outcomes. Methods. CDI cases were identified from population-based surveillance. Multivariate regression models were used to evaluate the associations of strain type with severe disease (ileus, toxic megacolon, or pseudomembranous colitis within 5 days; or white blood cell count ≥15,000/mm(3) within one day of positive test), severe outcome (intensive care unit admission after positive test, colectomy for C. difficile infection, or death within 30 days of positive test), and death within 14 days of positive test. Results. Strain typing results were available for 2,057 cases. Severe disease occurred in 363 (17.7%) cases, severe outcome in 100 (4.9%), and death within 14 days in 56 (2.7%). The most common strain types were NAP1 (28.4%), NAP4 (10.2%) and NAP11 (9.1%). In unadjusted analysis, NAP1 was associated with greater odds of severe disease than other strains. After controlling for patient risk factors, healthcare exposure, and antibiotic use, NAP1 was associated with severe disease (adjusted odds ratio [aOR] 1.74, 95% confidence interval [CI], 1.36-2.22), severe outcome (aOR 1.66, 95% CI, 1.09-2.54), and death within 14 days (aOR 2.12, 95% CI, 1.22-3.68). Conclusion. NAP1 was the most prevalent strain and a predictor of severe disease, severe outcome, and death. Strategies to reduce NAP1 prevalence, such as antibiotic stewardship to reduce fluoroquinolone use, might reduce CDI morbidity.

PMID: 24604900 [PubMed - as supplied by publisher]

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Mar 072014
 
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Risk Estimation for Recurrent Clostridium Difficile Infection Based on Clinical Factors.

Clin Infect Dis. 2014 Mar 5;

Authors: D'Agostino RB, Collins SH, Pencina KM, Kean Y, Gorbach S

Abstract
Background. The incidence of Clostridium difficile infection (CDI) has risen dramatically during the last decade. Although patients respond well to medical therapy such as vancomycin, 20-30% of patients treated suffer a recurrence of CDI. Methods. We developed a simple/practical scoring rule (logistic regression model) for recurrent CDI using data from two large Phase 3 clinical trials (www.clinicaltrials.gov: study NCT00314951 and study NCT00468728). 77 baseline CDI factors were classified: demographics, co-morbidity, medications, vital signs, laboratory tests, severity and symptoms. Predictors with the highest discrimination in each class (using Receiver Operating Characteristics Curve) were selected. For the final model, stepwise selection was performed. Discrimination, calibration and internal validation were used to assess the model. Results. The final model with a simple scoring rule was developed. It includes four independent risk factors which are readily available when the patient makes initial contact: age (<75 vs. ≥75years), number of unformed bowel movements during previous 24 hours (<10 vs. ≥10), serum creatinine levels (<1.2 mg/dL, ≥1.2 mg/dL) and prior episode of CDI (yes vs. no). In addition, the model includes choice of treatment (vancomycin or fidaxomicin). Conclusions. The prediction model for recurrence may be useful for treatment decision.

PMID: 24599770 [PubMed - as supplied by publisher]

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Dec 262013
 
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Fecal Microbiota Transplantation: A Practical Update for the Infectious Disease Specialist.

Clin Infect Dis. 2013 Dec 23;

Authors: Moore T, Rodriguez A, Bakken JS

Abstract
Fecal microbiota transplantation (FMT) has been shown to be a superior therapeutic modality for the treatment of recurrent Clostridium difficile infection (RCDI). Recently the US Food and Drug Administration (FDA) determined that human stool should be classified as a biological agent and its use should be regulated to ensure patient safety. Consequently, the FDA determined that prescribers of FMT must possess an approved investigational new drug (IND) permit to administer FMT for the purpose of conducting research or treating any gastrointestinal condition other than RCDI. Although an IND is not required for the use of FMT to treat RCDI, an IND is strongly encouraged and may ultimately be required. This article provides step-by-step guidance to infectious disease specialists on how to navigate the regulatory requirements and be successful at obtaining an IND before they can begin to use FMT as part of their clinical practice.

PMID: 24368622 [PubMed - as supplied by publisher]

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