Showing papers by "John W. Baddley published in 2014"

Endemic fungal infections in solid organ and hematopoietic cell transplant recipients enrolled in the Transplant-Associated Infection Surveillance Network (TRANSNET)

Abstract: Background Invasive fungal infections are a major cause of morbidity and mortality among solid organ transplant (SOT) and hematopoietic cell transplant (HCT) recipients, but few data have been reported on the epidemiology of endemic fungal infections in these populations. Methods Fifteen institutions belonging to the Transplant-Associated Infection Surveillance Network prospectively enrolled SOT and HCT recipients with histoplasmosis, blastomycosis, or coccidioidomycosis occurring between March 2001 and March 2006. Results A total of 70 patients (64 SOT recipients and 6 HCT recipients) had infection with an endemic mycosis, including 52 with histoplasmosis, 9 with blastomycosis, and 9 with coccidioidomycosis. The 12-month cumulative incidence rate among SOT recipients for histoplasmosis was 0.102%. Occurrence of infection was bimodal; 28 (40%) infections occurred in the first 6 months post transplantation, and 24 (34%) occurred between 2 and 11 years post transplantation. Three patients were documented to have acquired infection from the donor organ. Seven SOT recipients with histoplasmosis and 3 with coccidioidomycosis died (16%); no HCT recipient died. Conclusions This 5-year multicenter prospective surveillance study found that endemic mycoses occur uncommonly in SOT and HCT recipients, and that the period at risk extends for years after transplantation.

Antibiotic Utilization for Acute Respiratory Tract Infections in U.S. Emergency Departments

Abstract: Inappropriate use of antibiotics for acute respiratory tract infections (ARTIs) has decreased in many outpatient settings. For patients presenting to U.S. emergency departments (EDs) with ARTIs, antibiotic utilization patterns are unclear. We conducted a retrospective cohort study of ED patients from 2001 to 2010 using data from the National Hospital Ambulatory Medical Care Survey (NHAMCS). We identified patients presenting to U.S. EDs with ARTIs and calculated rates of antibiotic utilization. Diagnoses were classified as antibiotic appropriate (otitis media, sinusitis, pharyngitis, tonsillitis, and nonviral pneumonia) or antibiotic inappropriate (nasopharyngitis, unspecified upper respiratory tract infection, bronchitis or bronchiolitis, viral pneumonia, and influenza).There were 126 million ED visits with a diagnosis of ARTI, and antibiotics were prescribed in 61%. Between 2001 and 2010, antibiotic utilization decreased for patients aged <5 presenting with antibiotic-inappropriate ARTI (rate ratio [RR], 0.94; confidence interval [CI], 0.88 to 1.00). Utilization also decreased significantly for antibiotic-inappropriate ARTI patients aged 5 to 19 years (RR, 0.89; CI, 0.85 to 0.94). Utilization remained stable for antibiotic-inappropriate ARTI among adult patients aged 20 to 64 years (RR, 0.99; CI, 0.97 to 1.01). Among adults, rates of quinolone use for ARTI increased significantly from 83 per 1,000 visits in 2001 to 2002 to 105 per 1,000 in 2009 to 2010 (RR, 1.08; CI, 1.03 to 1.14). Although significant progress has been made toward reduction of antibiotic utilization for pediatric patients with ARTI, the proportion of adult ARTI patients receiving antibiotics in U.S. EDs is inappropriately high. Institution of measures to reduce inappropriate antibiotic use in the ED setting is warranted.

Non-viral opportunistic infections in new users of tumour necrosis factor inhibitor therapy: results of the SAfety Assessment of Biologic ThERapy (SABER) Study

Abstract: Objectives To determine among patients with autoimmune diseases in the USA whether the risk of non-viral opportunistic infections (OI) was increased among new users of tumour necrosis factor α inhibitors (TNFI), when compared to users of non-biological agents used for active disease. Methods We identified new users of TNFI among cohorts of rheumatoid arthritis (RA), inflammatory bowel disease and psoriasis-psoriatic arthritis-ankylosing spondylitis patients during 1998–2007 using combined data from Kaiser Permanente Northern California, two pharmaceutical assistance programmes for the elderly, Tennessee Medicaid and US Medicaid/Medicare programmes. We compared incidence of non-viral OI among new TNFI users and patients initiating non-biological disease-modifying antirheumatic drugs (DMARD) overall and within each disease cohort. Cox regression models were used to compare propensity-score and steroid- adjusted OI incidence between new TNFI and non-biological DMARD users. Results Within a cohort of 33 324 new TNFI users we identified 80 non-viral OI, the most common of which was pneumocystosis (n=16). In the combined cohort, crude rates of non-viral OI among new users of TNFI compared to those initiating non-biological DMARD was 2.7 versus 1.7 per 1000-person-years (aHR 1.6, 95% CI 1.0 to 2.6). Baseline corticosteroid use was associated with non-viral OI (aHR 2.5, 95% CI 1.5 to 4.0). In the RA cohort, rates of non-viral OI among new users of infliximab were higher when compared to patients newly starting non-biological DMARD (aHR 2.6, 95% CI 1.2 to 5.6) or new etanercept users (aHR 2.9, 95% CI 1.5 to 5.4). Conclusions In the USA, the rate of non-viral OI was higher among new users of TNFI with autoimmune diseases compared to non-biological DMARD users.

Risk of Hospitalized Bacterial Infections Associated With Biologic Treatment Among US Veterans With Rheumatoid Arthritis

Abstract: Objective The comparative risk of infection associated with non–anti–tumor necrosis factor (anti-TNF) biologic agents is not well established. Our objective was to compare risk for hospitalized infections between anti-TNF and non–anti-TNF biologic agents in US veterans with rheumatoid arthritis (RA). Methods Using 1998–2011 data from the US Veterans Health Administration, we studied RA patients initiating rituximab, abatacept, or anti-TNF therapy. Exposure was based upon days supplied (injections) or usual dosing intervals (infusions). Treatment episodes were defined as new biologic agent use. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) for hospitalization for a bacterial infection were estimated from Cox proportional hazards models, adjusting for potential confounders. Results Among 3,152 unique RA patients contributing 4,158 biologic treatment episodes to rituximab (n = 596), abatacept (n = 451), and anti-TNF agents (n = 3,111), the patient mean age was 60 years and 87% were male. The most common infections were pneumonia (37%), skin/soft tissue (22%), urinary tract (9%), and bacteremia/sepsis (7%). Hospitalized infection rates per 100 person-years were 4.4 (95% CI 3.1–6.4) for rituximab, 2.8 (95% CI 1.7–4.7) for abatacept, and 3.0 (95% CI 2.5–3.5) for anti-TNF. Compared to etanercept, the adjusted rate of hospitalized infection was not different for adalimumab (HR 1.4, 95% CI 0.9–2.2), abatacept (HR 1.1, 95% CI 0.6–2.1), or rituximab (HR 1.4, 0.8–2.6), although it was increased for infliximab (HR 2.3, 95% CI 1.3–4.0). Infection risk was greater for those taking prednisone >7.5 mg/day (HR 1.8, 95% CI 1.3–2.7) and in the highest quartile of C-reactive protein (HR 2.3, 95% CI 1.4–3.8) and erythrocyte sedimentation rate (HR 4.1, 95% CI 2.3–7.2) compared to the lowest quartile. Conclusion In older, predominantly male US veterans with RA, the risk of hospitalized bacterial infections associated with rituximab or abatacept was similar to etanercept.

Immunosuppression regimen and the risk of acute rejection in HIV-infected kidney transplant recipients.

Abstract: BACKGROUND Kidney transplantation (KT) is the treatment for end-stage renal disease in appropriate HIV-positive individuals. However, acute rejection (AR) rates are over twice those of HIV-negative recipients. METHODS To better understand optimal immunosuppression for HIV-positive KT recipients, we studied associations between immunosuppression regimen, AR at 1 year, and survival in 516 HIV-positive and 93,027 HIV-negative adult kidney-only recipients using Scientific Registry of Transplant Recipients data from 2003 to 2011. RESULTS Consistent with previous reports, HIV-positive patients had twofold higher risk of AR (adjusted relative risk [aRR], 1.77; 95% confidence interval [CI], 1.45-2.2; P<0.001) than their HIV-negative counterparts as well as a higher risk of graft loss (adjusted hazard ratio, 1.51; 95% CI, 1.18-1.94; P=0.001), but these differences were not seen among patients receiving antithymocyte globulin (ATG) induction (aRR for AR, 1.16; 95% CI, 0.41-3.35, P=0.77; adjusted hazard ratio for graft loss, 1.54; 95% CI, 0.73-3.25; P=0.26). Furthermore, HIV-positive patients receiving ATG induction had a 2.6-fold lower risk of AR (aRR, 0.39; 95% CI, 0.18-0.87; P=0.02) than those receiving no antibody induction. Conversely, HIV-positive patients receiving sirolimus-based therapy had a 2.2-fold higher risk of AR (aRR, 2.15; 95% CI, 1.20-3.86; P=0.01) than those receiving calcineurin inhibitor-based regimens. CONCLUSION These findings support a role for ATG induction, and caution against the use of sirolimus-based maintenance therapy, in HIV-positive individuals undergoing KT.

Reduction in False-Positive Aspergillus Serum Galactomannan Enzyme Immunoassay Results Associated with Use of Piperacillin-Tazobactam in the United States

Abstract: Piperacillin-tazobactam (PTZ) is known to cause false-positive results in the Platelia Aspergillus enzyme-linked immunoassay (EIA), due to contamination with galactomannan (GM) We tested 32 lots of PTZ and 27 serum specimens from patients receiving PTZ GM was not detected in the lots of PTZ; one serum specimen (37%) was positive PTZ formulations commonly used in the United States today appear to be a rare cause for false-positive GM results

Pneumocystis jirovecii pneumonia in patients receiving tumor-necrosis-factor-inhibitor therapy: implications for chemoprophylaxis.

Abstract: Pneumocystis jirovecii pneumonia (PJP) is an important opportunistic infection that has been increasingly reported in patients with rheumatic disease. Reported incidence among patients taking TNF inhibitors (TNFi) has varied, but has usually been low. Still, disease causes significant mortality among those affected and must be considered in patients with rheumatological disease presenting with dyspnea and cough. Diagnosis can be difficult in the non-HIV population, and our understanding of the epidemiology and natural history after exposure is changing. Trimethoprim-sulfamethoxazole is believed to be the most effective agent for treatment and prophylaxis, but is associated with significant adverse effects. Given the low incidence reported in most studies of patients on TNFi, prophylaxis is probably not beneficial for this patient population as a whole.

A case report of progressive multifocal leucoencephalopathy (PML) associated with adalimumab

Abstract: Progressive multifocal leucoencephalopathy (PML) is a demyelinating disease of the central nervous system caused by polyomavirus JC. It results from lytic infection of glial cells and is often fatal.1 ,2 A common risk factor for PML is immunosuppression due to HIV infection or malignancy (or its treatment). PML has also been reported in those using immunomodulation therapies.3 A previous study estimated incidence of PML at 0.2/100 000 among patients with autoimmune diseases who did not have HIV or malignancy. Based on the single case of PML exposed to a biological agent, another study reported the incidence rate (IR) of PML was 2.3 (95% CI 0.1 to 71) per 100 000 person-years in patients who were exposed to biological agents and 0.8 (95% CI 0.2 to 2.5) per 100 000 person-years in those not exposed to biological agents.4 Cases of PML associated …

Mortality After Clinical Management of Aids-Associated Cryptococcal Meningitis in Kenya

Abstract: Background : Cryptococcal meningitis (CM) is an increasingly prevalent infection among HIV/AIDS patients and is becoming a leading cause of morbidity and mortality in Africa. The short-term prognosis and management of patients with CM may be improved by identifying factors leading to mortality in patients with CM. Objective : To assess the clinical management and mortality associated with cryptococcal meningitis (CM) in patients with acquired immunodeficiency syndrome (AIDS) in Kenya. Design : A retrospective study. Setting : Kenyatta National Hospital and Mbagathi District Hospital, between August 2008 and March 2009. Subjects : Seventy six HIV-infected patients confirmed to be CM positive. Results : Results show that 30 (40%) of 76 patients diagnosed with CM died during hospitalisation after a median hospital stay of ten days (range, 2-73 days). Significant predictors of mortality in the univariate model were Mycobacterium tuberculosis (TB) co-infection (P = 0.04), having been diagnosed with a co-morbid condition such as diabetes mellitus, oral candidiasis and hypertension (P = 0.01), and a low median CD4+ T lymphocyte count (P < 0.001). The multivariable model revealed that male sex, previous or current anti-retroviral therapy (ART) at admission and CD4+ T lymphocyte count less than 50 were significant predictors of mortality. Conversely, a minimum of two weeks of amphotericin B treatment (P < 0.001), initiation of ART (P = 0.007) and monitoring of creatinine and electrolyte levels (P = 0.02) were significantly associated with survival in the univariate model. Conclusions : CM-associated mortality in Kenya is high; there is an opportunity to improve the management and the short-term outcomes of hospitalised HIV positive patients with CM in Kenya.

Mollaret's meningitis.

Abstract: A 48-year-old man presented with a 2 day history of fever, headache, chills, neck stiff ness, and nausea and vomiting. He had a history of two episodes of viral meningitis, which occurred 30 and 13 years before this presentation. An examination confi rmed meningism without focal neurological defi cits. Results of CSF tests showed protein concentration of 120 mg/dL (normal 12–60 mg/dL), normal glucose concentration, red blood cells 26 cells/μL, and white blood cells 327 cells/μL (10% neutrophils, 84% lymphocytes, 6% monocytes). CSF Gram stain and cultures were negative. Diff -Quik stain of CSF showed many large activated monocytes with several deep nuclear clefts visible as so-called cloverleaf nucleus (green arrowhead, fi gure A), footprintshaped nucleus (white arrowhead, fi gure B), and beanshaped nucleus (green arrow, fi gure C), with a background of normal monocytes (black arrowheads, fi gure A, B) and lymphocytes (black arrows, fi gure A, B). The features of these activated monocytes were compatible with those of Mollaret’s cells, and CSF herpes simplex virus type 2 (HSV2) PCR assay was positive. Large degenerated monocytes were present as ghost cells (asterisks, fi gure B), observed in the slide background. A diagnosis of Mollaret’s meningitis was made. The patient was discharged without antimicrobial therapy and recovered completely. Mollaret’s meningitis was fi rst described by the French neurologist Pierre Mollaret in 1944. The disease is characterised by recurrent (at least three episodes), benign (no long-term sequelae) and brief (2–5 day) episodes of aseptic lymphocytic meningitis, alternating with symptom-free interval, mostly caused by HSV2 infection. The disease is usually self-limited, and antiviral therapy is routinely not recommended. It is therefore also known as recurrent benign lymphocytic meningitis. Typically, results of CSF studies show hypercellularity and predominantly lymphocytic pleocytosis with positive HSV2 DNA by PCR assay. Cellular cytomorphological features of CSF charac teristically show diagnostic Mollaret’s cells, which are multiple activated large monocytes with deep nuclear clefts giving rise to various convoluted, eye-catching shapes of nuclei, such as cloverleaf, bean, and footprint patterns. Usually degenerated monocytes known as ghost cells are present, scattered at the background of the slide. Recognition of these cells in the CSF is crucial for a timely and accurate diagnosis because it could prevent extensive and costly diagnostic studies and antimicrobial therapies.

Race and invasive fungal infection in solid organ transplant recipients.

Abstract: Health disparities in access to solid organ transplantation (SOT) and graft survival are well recognized, but there are limited data on the relationship of race to risk of invasive fungal infection (IFI) among SOT recipients. We conducted a case-control study using data from the Transplant-Associated Infection Surveillance Network (TRANSNET) to investigate race and IFI. Cases ( n= 1,214) and controls ( n= 16,550) were compared on demographic variables using chi-square, and the relationship between race and IFI was assesses with unconditional logistic regression. Compared to White transplant patients, Blacks had similar odds of developing IFI (OR=.97, 95% CI 0.82– 1.15, P =.7125), while participants who identified as other ethnicity were less likely to develop IFI (OR=.56, 95% CI .41–.75, P <.001). Blacks, when compared to White patients, were at increased odds of developing cryptococcal infection (OR 2.19, 95%CI 1.35–3.54, P =.002). Despite pharmacogenetic differences, Black transplant recipients were not more likely overall to develop IFI compared to White transplant recipients. ( Ethn Dis . 2014;24[3]:382–385

Reply to "acute sinusitis and pharyngitis as inappropriate indications for antibiotic use".

Abstract: We thank Drs. Sanchez and Hicks for [their constructive comments][1], which underscore current limitations of diagnostic coding data ([1][2], [2][3]). While we were not able to determine with certainty if patients were immunocompromised, we excluded any patient admitted to the hospital, which likely