Evaluation of cytomegalovirus "Blips" in high-risk kidney/kidney-pancreas transplant recipients.

BACKGROUND: Cytomegalovirus (CMV) is a significant cause of morbidity and mortality after solid organ transplantation. While guidelines suggest using highly sensitive QNAT assays for CMV detection, there is no defined viral load to guide initiation of preemptive therapy. This study evaluates the progression to quantifiable CMV (DNAemia) following a CMV "blip" in high-risk (D+/R) kidney/kidney-pancreas (KP) transplant recipients. METHODS: This is a single center, retrospective study. A CMV "blip" was defined as the first positive QNAT assay below the level of quantification (<1.37 × 102 IU/ml or <200 viral copies). Subsequent CMV QNAT assays were followed to assess the progression from blip to CMV DNAemia for 1 year following transplant. RESULTS: A total of 134 patients were included in the study. Fifty-three (39.6%) patients had their first positive CMV QNAT value below the level of quantification, a "CMV blip." Of these 53 patients, 69.8% (n = 37) progressed to DNAemia while 30.2% (n = 16) did not. The median time from transplant to the first CMV blip was 68 (46-97) days and most patients with viral blips (71.1%) were on prophylaxis. No differences in patient characteristics were found among those who progressed from blip to DNAemia and those who only had a blip. CONCLUSIONS: In CMV high-risk kidney/KP transplant recipients, CMV blips progressed to CMV DNAemia in the majority of cases. This progression typically occurred 2-3 weeks following the initial blip. CMV blips are common early posttransplant despite prophylaxis and likely represent an early marker of CMV infection.

Bloodstream infections among intestinal and multivisceral transplant recipients.

OBJECTIVE: To examine the etiologies, risk factors, and microbiology of bloodstream infections (BSIs) among intestinal and multivisceral transplant recipients in the 2-year post-operative period. METHODS: A retrospective medical record review of adult intestinal or multivisceral transplant recipients between 2003 and 2015. Descriptive statistics were used to describe cohort data. Logistic regression was used to assess factors related to BSIs using a backward selection process. RESULTS: One-hundred and six intestinal or multivisceral transplants were performed in 103 individuals. Fifty-eight percent (n = 62) developed a BSI in the 2-year post-operative period with a median time to first BSI of 53 days (interquartile range [IQR] 15, 169). The majority of BSIs were catheter related 38% (n = 58) when the source was known. Common microbiological isolates included enterococcus 20% (n = 36/174), coagulase-negative staphylococcus 14% (n = 23), and 12% Klebsiella spp (n = 21). Forty-seven percent (n = 17) of the enterococci were resistant to vancomycin, and 14% (n = 10/70) of the gram negatives were extended spectrum beta-lactamase (ESBL) producers. In adjusted analyses, (OR: 0.200 95% CI: 0.2, 0.514, P = .009) men were less likely to have a BSI. Transplant recipient age, allograft type, comorbidities, rejection, and length of stay were not noted to be risk factors for development of BSIs in our cohort. Mortality at 2-years post-transplant was similar for those who did not develop a BSI and those that developed infection, P = .5028. CONCLUSIONS: BSIs are a common complication of intestinal transplantation, and central venous catheters were a common source. Interventions such as early catheter removal should be implemented to prevent infections in this population. Female sex association with BSI requires further investigation.

Cancer Incidence and Cancer Screening Practices Among a Cohort of Persons Receiving HIV Care in Washington, DC.

In this era of effective combination antiretroviral therapy the incidence of AIDS defining cancers (ADCs) is projected to decline while the incidence of certain non-AIDS defining cancers (NADCs) increases. Some of these NADCs are potentially preventable with appropriate cancer screening. We examined cancer incidence, screening eligibility, and receipt of screening among persons actively enrolled in the DC Cohort, a longitudinal observational cohort of PLWH, between 2011 and 2017. Cancer screening eligibility was determined based on age, sex, smoking history and co-morbidity data available and published national guidelines. The incidence rate of NADCs was 12.1 (95% CI 10.7, 13.8) and ADCs 1.6 (95% CI 0.6, 4.6) per 1000 person-years. The most common incident NADCs were breast 2.6 (95% CI 0.5,1 2.1), prostate 2.3 (95% CI 1.2, 4.3), and non-melanoma skin 1.2 (95% CI 0.6, 2.3) incident diagnoses/cases per 1000 person-years. Among cohort sites where receipt of cancer screening was assessed, less than 60% of eligible participants had any ascertained anal HPV, breast, cervical, colorectal, hepatocellular carcinoma, or lung cancer screening. In this cohort of PLWH, there were more incident NADCs versus ADCs in contrast to earlier cohort studies where ADCs predominated. Despite a large eligible population there were low rates of screening. Implementation of cancer screening is an important component of care among PLWH.

Intra-abdominal infections among adult intestinal and multivisceral transplant recipients in the 2-year post-operative period.

BACKGROUND: Intestinal and multivisceral transplantations are treatment options for patients with intestinal failure. Transplantation is often complicated by abdominal and/or bloodstream infections in the post-operative period. METHODS: A retrospective chart review of all adults who underwent intestinal or multivisceral transplantation at our institution from 2003 to 2015 was performed. Data were collected for 2 years post transplant. RESULTS: A total of 106 intestinal or multivisceral transplants were performed in 103 patients. The median age at the time of transplant was 44 (IQR: 34-52) with 55% (n = 58) male and 45% (n = 48) female. There were 46 (43%) intra-abdominal infections post transplant among the 103 patients, and six transplant recipients (13%) developed concurrent bloodstream infections. The median time to first intra-abdominal infection was 23 days (IQR: 10-48). For those with organisms isolated in culture, forty-seven percent of the isolates were gram negative, 39% gram positive, 7% anaerobes, and 7% yeast. The most common isolates were enterococci at 28%, E. coli at 14%, and Klebsiella spp at 13%. Sixty-three percent of the enterococci were vancomycin-resistant enterococci (VRE), and 22% of the gram-negative isolates were extended spectrum beta-lactamases (ESBLs). Patients with intra-abdominal infections had longer hospital post-transplant length of stays at a median of 35 days (IQR: 25-48) vs 23 days (IQR: 17-33) for those without infections, P = .0012. There was no difference in all-cause mortality in patients with or without intra-abdominal infections, P = .654. CONCLUSIONS: Intra-abdominal infections are common in intestinal or multivisceral transplant recipients, but despite this complication, we found no increased risk of mortality. These transplant recipients are also at risk for infection with drug-resistant organisms.

Bartonella Endocarditis and Pauci-Immune Glomerulonephritis: A Case Report and Review of the Literature.

Among culture-negative endocarditis in the United States, Bartonella species are the most common cause, with Bartonella henselae and Bartonella quintana comprising the majority of cases. Kidney manifestations, particularly glomerulonephritis, are common sequelae of infectious endocarditis, with nearly half of all Bartonella patients demonstrating renal involvement. Although a pauci-immune pattern is a frequent finding in infectious endocarditis-associated glomerulonephritis, it is rarely reported in Bartonella endocarditis. Anti-neutrophil cytoplasmic antibody (ANCA) positivity can be seen with many pathogens causing endocarditis and has been previously reported with Bartonella species. In addition, ANCA-associated vasculitis can also present with renal and cardiac involvement, including noninfectious valvular vegetations and pauci-immune glomerulonephritis. Given the overlap in their clinical presentation, it is difficult to differentiate between Bartonella endocarditis and ANCA-associated vasculitis but imperative to do so to guide management decisions. We present a case of ANCA-positive Bartonella endocarditis with associated pauci-immune glomerulonephritis that was successfully treated with medical management alone.

Tracking colistin-treated patients to monitor the incidence and outcome of carbapenem-resistant Gram-negative infections.

BACKGROUND: Existing surveillance mechanisms may underestimate the incidence of carbapenem-resistant gram-negative infections (CRGNIs). Although carbapenem resistance increases the risk of death, the trend in mortality over time is unknown. METHODS: A retrospective cohort study was conducted at 40 academic medical centers using a discharge database to identify adult hospital admissions without cystic fibrosis in 2006-2012 and received intravenous colistin for >3 consecutive days or died during therapy (termed colistin cases). The primary outcomes were the number of colistin cases per 100,000 admissions per year and change in the hospital mortality rate over time compared with the rate of discharges to home. Secondary outcomes included median overall and intensive care unit lengths of stay. RESULTS: From 2006 to 2012, a total of 5011 unique patients were identified as colistin cases. The number per 100,000 admissions per year increased from 35.56 to 92.98 during the 7-year study (P < .001). The odds of in-hospital death among colistin cases (compared with discharge to home) decreased by a mean of 5.2%/y (P = .04), whereas discharge to an institution (P = .24) or hospice (P = .89) remained steady over time. The median overall and intensive care unit lengths of stay decreased by 7.5 and 6 days, respectively (P < .001). In a 4-hospital chart review, 81.6% of colistin cases were found to have culture-positive CRGNIs. Conversely, 53% of extensively drug-resistant bloodstream CRGNIs at 2 of these hospitals met colistin case criteria. CONCLUSIONS: Colistin cases represent a severely ill population with a high probability of having culture-confirmed CRGNIs. Colistin tracking is a novel strategy for monitoring the incidence and mortality of CRGNIs, particularly those caused by extensively drug-resistant bacteria. Although the incidence of colistin cases nearly tripled within 7 years, more of these patients are surviving hospitalization and going home.

Attributable mortality from extensively drug-resistant gram-negative infections using propensity-matched tracer antibiotic algorithms.

BACKGROUND: Tracer antibiotic algorithms using administrative data were investigated to estimate mortality attributable to extensively drug-resistant gram-negative infections (GNIs). METHODS: Among adult inpatients coded for GNIs, colistin cases and 2 comparator cohorts (non-carbapenem ß-lactams or carbapenems) treated for ≥4 consecutive days, or died while receiving the antibiotic, were separately propensity score-matched (1:2). Attributable mortality was the in-hospital mortality difference among propensity-matched groups. Infection characteristics and sepsis severity influences on attributable mortality were examined. Algorithm accuracy was assessed by chart review. RESULTS: Of 232,834 GNIs between 2010 and 2013 at 79 hospitals, 1,023 per 3,350 (30.5%) colistin and 9,188 per 105,641 (8.7%) ß-lactam (non-carbapenem) comparator cases died. Propensity-matched colistin and ß-lactam case mortality was 29.2% and 16.6%, respectively, for an attributable mortality of 12.6% (95% confidence interval 10.8-14.4%). Attributable mortality varied from 11.0% (7.5%-14.7%) for urinary to 15.5% (12.6%-18.4%) for respiratory (P < .0001), and 4.6% (2.1%-7.4%) for early (≤4 days) to 16.6% (14.3%-18.9%) for late-onset infections (P < .0001). Attributable mortality decreased to 7.5% (5.6%-9.4%) using a carbapenem comparator cohort but increased 9-fold in patients coded for severe sepsis or septic shock (P < .0001). Our colistin algorithm had a positive predictive value of 60.4% and sensitivity of 65.3%. CONCLUSIONS: Mortality attributable to treatment-limiting resistance during GNIs varied considerably by site, onset, and severity of infection.

Occupational transmission of Acinetobacter baumannii from a United States serviceman wounded in Iraq to a health care worker.

BACKGROUND: Acinetobacter baumannii is increasingly recognized as being a significant pathogen associated with nosocomial outbreaks in both civilian and military treatment facilities. Current analyses of these outbreaks frequently describe patient-to-patient transmission. To date, occupational transmission of A. baumannii from a patient to a health care worker (HCW) has not been reported. We initiated an investigation of an HCW with a complicated case of A. baumannii pneumonia to determine whether a link existed between her illness and A. baumannii-infected patients in a military treatment facility who had been entrusted to her care. METHODS: Pulsed-field gel electrophoresis and polymerase chain reaction/electrospray ionization mass spectrometry, a form of multilocus sequencing typing, were done to determine clonality. To further characterize the isolates, we performed a genetic analysis of resistance determinants. RESULTS AND CONCLUSIONS: A "look-back" analysis revealed that the multidrug resistant A. baumannii recovered from the HCW and from a patient in her care were indistinguishable by pulsed-field gel electrophoresis. In addition, polymerase chain reaction/electrospray ionization mass spectrometry indicated that the isolates were similar to strains of A. baumannii derived from European clone type II (Walter Reed Army Medical Center strain type 11). The exposure of the HCW to the index patient lasted for only 30 min and involved endotracheal suctioning without use of an HCW mask. An examination of 90 A. baumannii isolates collected during this investigation showed that 2 major and multiple minor clone types were present and that the isolates from the HCW and from the index patient were the most prevalent clone type. Occupational transmission likely occurred in the hospital; HCWs caring for patients infected with A. baumannii should be aware of this potential mode of infection spread.

Serious infection from Staphylococcus aureus in 2 HIV-infected patients receiving fusion inhibitor therapy.

Fusion inhibitors are novel antiretroviral agents, administered as subcutaneous injections, approved for use in treatment-experienced HIV-infected patients. HIV-infected patients are at increased risk for Staphylococcus aureus colonization, specifically with methicillin-resistant S aureus (MRSA), and subsequent systemic infection. We present the cases of 2 patients without a history of MRSA infection in whom a series of severe S aureus infections developed after fusion inhibitor therapy.

HIV type 1 chemokine coreceptor use among antiretroviral-experienced patients screened for a clinical trial of a CCR5 inhibitor: AIDS Clinical Trial Group A5211.

BACKGROUND: Chemokine coreceptor use impacts both the natural history of human immunodeficiency virus type 1 (HIV-1) disease and the potential use of a new class of antiretroviral agents, the CCR5 inhibitors. METHODS: We analyzed HIV-infected patients who were screened for participation in Acquired Immunodeficiency Syndrome (AIDS) Clinical Trial Group protocol A5211, a phase 2b study of the investigational CCR5 inhibitor vicriviroc involving antiretroviral-experienced subjects. Screening CD4(+) cell count, HIV-1 plasma RNA level, HIV-1 genotype, and chemokine coreceptor use phenotype were determined. The univariate and multivariate association of subject characteristics with coreceptor use was assessed by logistic regression. RESULTS: Coreceptor use was determined for 391 subjects: 197 (50%) had virus that used the CCR5 coreceptor (the R5 group), 178 [corrected] (46%) had dual-tropic or mixed HIV-1 populations that used both CCR5 and CXCR4 coreceptors (the D/M group), and 16 (4%) had virus that used the CXCR4 coreceptor (the X4 group). The D/M group had a significantly lower median CD4(+) cell count than the R5 virus group (103 cells/ micro L vs. 170 cells/ mu L; P<.001). No other characteristics were independently associated. Among 118 subjects who entered A5211 having R5 virus, 12 (10%) had D/M virus according to the results of a second coreceptor test conducted prior to starting treatment with the study drug. CONCLUSIONS: Infection with dual-tropic or mixed HIV-1 populations that use both CCR5 and CXCR4 is common among highly treatment-experienced patients, but infection with virus using CXCR4 alone is uncommon. Subjects in the D/M group had significantly lower CD4(+) cell counts than subjects in the R5 group. Evaluating coreceptor use will be important in the clinical development of CCR5 and CXCR4 inhibitors.

Reduced bone mineral density in human immunodeficiency virus-infected patients and its association with increased central adiposity and postload hyperglycemia.

Reduced bone mineral density (BMD) and abnormalities in fat redistribution, glucose homeostasis, and lipid metabolism are prevalent among HIV-infected patients on highly active antiretroviral therapy (HAART). The relationship between the metabolic and skeletal complications of HIV is unclear. Fifty-one HIV patients on HAART (aged 30-54 yr, 86% male) and 21 HIV-negative control subjects (aged 31-51 yr, 82% male) were examined with oral glucose tolerance testing, a fasting lipid profile, and dual x-ray absorptiometry, and markers of bone formation (serum osteocalcin) and resorption (urinary deoxypyridinoline). HIV-infected subjects had a higher prevalence of either osteopenia or osteoporosis (World Health Organization criteria) at the spine, hip, or forearm, compared with HIV-negative controls (63% vs. 32%, P = 0.02) and evidence of increased bone resorption (urine deoxypyridinoline, 14.7 +/- 6.5 vs. 10.9 +/- 2.5 nmol/mmol creatinine, P = 0.012). Among the HIV-infected patients, those with reduced bone mineral density (n = 32) were similar to the group with normal BMD (n = 19) in the use of protease inhibitors, duration of HAART therapy, or other demographic variables. Plasma glucose 2 h after a glucose load (odds ratio 1.02 per 1 mg/dl increase, 95% confidence interval 1.01-1.05, P = 0.009) and central adiposity (trunk fat/total fat) (odds ratio 1.09 per 1% ratio increase, 95% confidence interval 1.00-1.18, P = 0.012) were associated with reduced BMD. These associations remained significant in a multivariate model including age and body mass index. Bone resorption was associated with female gender (P < 0.001) and non-high-density lipoprotein cholesterol (P = 0.034) in a multivariate linear regression model controlling for age, body mass index, protease inhibitor use, duration of HAART, and extremity fat. Reduced BMD is prevalent in HIV-infected patients on HAART and is related to central adiposity and postload hyperglycemia. Bone resorption is independently associated with female gender and dyslipidemia. HIV-infected patients with metabolic abnormalities may represent a population that would benefit from bone density screening.

HIV-associated neurocognitive disorders: perspective on management strategies.

Potent combination antiretroviral therapy (ART) has resulted in dramatic improvements in AIDS-associated morbidity and mortality. Although combination ART has resulted in a significant reduction in HIV-associated dementia, the most severe of the HIV-associated neurocognitive disorders (HAND), the overall prevalence of HAND among this population is estimated at 40%. It has been recognized that the central nervous system (CNS) serves as a reservoir for HIV, and neuronal damage begins at the time of acute infection and persists due to chronic infection of microglial and perivascular macrophages. Although combination ART has resulted in virologic control in the plasma compartment, virologic breakthrough can potentially ensue within the CNS compartment due to limited ART drug exposure. The purpose of this review is to discuss the definition, clinical spectrum, and risk factors associated with HAND, review the pathogenesis of HAND, and address the pharmacologic challenges associated with ART drug exposure in the CNS compartment.

BK polyomavirus infection in the renal transplant recipient.

Renal transplant recipients continue to have progressive kidney dysfunction and renal graft loss has been attributed to emerging opportunistic infections, specifically BK virus (BKV). BKV is postulated to be selected by the new potent immunosuppressive medications and to be an important factor in graft failure. The prevalence of BKV nephropathy (BKVN) is estimated to be 1% to 10% and renal allograft loss from BKVN has been estimated to occur in up to 50% of affected recipients. With the increasing recognition of BKV infection using PCR assays coupled with the immediate reduction in immunosuppression for BKVN, the incidence of graft failure secondary to BKVN may be decreasing.

Infections in intestinal and multivisceral transplant recipients.

Intestinal and multivisceral transplantation has become an effective treatment option for patients with intestinal failure. More potent immunosuppressive therapy has resulted in a decreased incidence of acute rejection and has improved patient survival. However, infectious complications can cause significant morbidity both before and after transplantation. In comparison with other solid organ transplant recipients, these patients experience higher rates of acute allograft rejection, thus requiring higher levels of immunosuppression and escalating the risk of infection. This article reviews the most common infectious disease complications encountered, and proposes a potential temporal association for types of infections in this patient population.

Pharmacologic issues of antiretroviral agents and immunosuppressive regimens in HIV-infected solid organ transplant recipients.

HIV-positive patients are now undergoing solid organ transplantation at increasing rates, with successful outcomes. Transplantation in this unique patient population presents new challenges in the postoperative management of both antiretroviral regimens and immunosuppressive regimens. This review highlights the drug-drug interactions between commonly used immunosuppressive and antiretroviral agents. As more antiretroviral regimens are cautiously initiated in the posttransplant period, further research is needed to identify drug-drug interactions to minimize toxicities and improve long-term survival and graft function.

HIV-associated intracranial aneurysmal vasculopathy in adults.

Diffuse fusiform intracranial aneurysms have been reported in children with human immunodeficiency virus (HIV) for over 2 decades, but have only recently been reported in adults with HIV. Although these aneurysms have important clinical implications, their etiology and optimal therapy are unknown. We present a systematic review of diffuse intracranial fusiform aneurysmal vasculopathy in patients who are HIV-positive. We conducted a comprehensive literature search for relevant case reports and reviews published before February 2009. Patients were included if they had HIV infection and radiographic imaging consistent with fusiform aneurysmal vasculopathy. We identify 11 published adult cases of intracranial fusiform aneurysmal vasculopathy and describe 1 unpublished case from our own institution. Available data regarding clinical presentation, characteristic imaging findings, and treatment of this complex syndrome are reviewed. Adults with HIV-associated intracranial aneurysmal vasculopathy typically are significantly immunosuppressed and present with gross neurologic dysfunction. Characteristic radiographic findings include diffuse cerebral fusiform aneurysms with hemorrhage or infarct. Treatment of any active infection followed by the initiation of antiretroviral therapy and corticosteroids may be a reasonable approach in this complex syndrome.

Rhodococcus equi pulmonary-central nervous system syndrome: brain abscess in a patient on high-dose steroids--a case report and review of the literature.

Rhodococcus equi has emerged as an opportunistic pathogen usually causing necrotizing pneumonia in immunosuppressed patients but has been found increasingly in extrapulmonary sites. We report the 1st case of R. equi brain abscess in a patient receiving corticosteroid monotherapy and review the literature for risk factors and sites of infection.

Surgical algorithm for management of HIV lipodystrophy.

BACKGROUND: The accepted standard for treatment of human immunodeficiency virus disease, highly active antiviral therapy, may cause significant side effects, such as facial lipoatrophy and lipodystrophy. Facial wasting or a buffalo hump deformity may be pathognomonic for treated human immunodeficiency virus disease. In addition to facial wasting, cystic parotid degeneration may further distort the face. The authors outline the defects as a series of triangles defined by anatomical boundaries. METHODS: In a group of 27 patients, 17 were treated for buffalo hump (three isolated and 14 with associated facial wasting). Another 10 patients were treated for isolated facial wasting. RESULTS: The 14 patients who underwent liposuction of the buffalo hump with subsequent injection of the aspirate into the face had approximately 40 to 50 percent of the grafts survive. Recurrent or severely fibrous humps were treated with ultrasound-assisted liposuction. In six patients, autografts to the lypoatrophic face were utilized. Two patients undergoing gynecomastia reduction had successful grafting with the resected breast. Three patients with cystic degeneration of the parotid underwent superficial parotidectomy with rotation or grafting of the parotid into the defect, for a total of six individual procedures. CONCLUSION: The authors present an algorithm for treatment of buffalo hump and facial wasting deformities associated with human immunodeficiency virus lipodystrophy syndrome, with an emphasis on long-term results with autogenous tissue.

Ocular syphilis in HIV-positive patients receiving highly active antiretroviral therapy.

BACKGROUND: From October 2001 to October 2002, we have observed a surprisingly high incidence of ocular syphilis in human immunodeficiency virus-positive (HIV+) patients receiving highly active antiretroviral therapy at our clinic. METHODS: We conducted a retrospective chart and patient database review. RESULTS: From 1997 to 2002, 455 patients in our clinic were screened for syphilis; 320 were screened from 2001 to 2002; 7.3% of patients (33/455) were diagnosed with syphilis. During the past year, syphilis was diagnosed in 7.5% of patients (24/320), of whom 13% (3/24) had ocular syphilis. We estimate the prevalence of ocular syphilis in HIV+ patients on highly active antiretroviral therapy screened for syphilis to be 9% (3/33). Presenting symptoms included blurred vision, loss of vision, central scotomas, and bilateral ocular involvement. The most common ocular manifestation of syphilis was posterior chamber uveitis; one patient also had a retinal detachment. All patients demonstrated reactive rapid plasma reagin and fluorescent treponemal antibody absorption test results, cerebrospinal fluid pleocytosis, and elevated total protein. Each patient received a 21-day course of intravenous penicillin G (24 million units daily) with improvement of visual symptoms. CONCLUSION: Our data demonstrate an unexpectedly high incidence of ocular syphilis in our HIV+ patients receiving highly active antiretroviral therapy during the past year. A diagnosis of ocular syphilis should be considered in any HIV+ patient who presents with visual symptoms, irrespective of the patient's CD4 count.