Christopher Vinnard

Colistin- and Carbapenem-Resistant Escherichia coli Harboring mcr-1 and blaNDM-5, Causing a Complicated Urinary Tract Infection in a Patient from the United States

ABSTRACT Colistin is increasingly used as an antibiotic of last resort for the treatment of carbapenem-resistant Gram-negative infections. The plasmid-borne colistin resistance gene mcr-1 was initially identified in animal and clinical samples from China and subsequently reported worldwide, including in the United States. Of particular concern is the spread of mcr-1 into carbapenem-resistant bacteria, thereby creating strains that approach pan-resistance. While several reports of mcr-1 have involved carbapenem-resistant strains, no such isolates have been described in the United States. Here, we report the isolation and identification of an Escherichia coli strain harboring both mcr-1 and carbapenemase gene blaNDM-5 from a urine sample in a patient without recent travel outside the United States. The isolate exhibited resistance to both colistin and carbapenems, but was susceptible to amikacin, aztreonam, gentamicin, nitrofurantoin, tigecycline, and trimethoprim-sulfamethoxazole. The mcr-1- and blaNDM-5-harboring plasmids were completely sequenced and shown to be highly similar to plasmids previously reported from China. The strain in this report was first isolated in August 2014, highlighting an earlier presence of mcr-1 within the United States than previously recognized. IMPORTANCE Colistin has become the last line of defense for the treatment of infections caused by Gram-negative bacteria resistant to multiple classes of antibiotics, in particular carbapenem-resistant Enterobacteriaceae (CRE). Resistance to colistin, encoded by the plasmid-borne gene mcr-1, was first identified in animal and clinical samples from China in November 2015 and has subsequently been reported from numerous other countries. In April 2016, mcr-1 was identified in a carbapenem-susceptible Escherichia coli strain from a clinical sample in the United States, followed by a second report from a carbapenem-susceptible E. coli strain originally isolated in May 2015. We report the isolation and identification of an E. coli strain harboring both colistin (mcr-1) and carbapenem (blaNDM-5) resistance genes, originally isolated in August 2014 from urine of a patient with recurrent urinary tract infections. To our knowledge, this is the first report in the United States of a clinical bacterial isolate with both colistin and carbapenem resistance, highlighting the importance of active surveillance efforts for colistin- and carbapenem-resistant organisms. Colistin has become the last line of defense for the treatment of infections caused by Gram-negative bacteria resistant to multiple classes of antibiotics, in particular carbapenem-resistant Enterobacteriaceae (CRE). Resistance to colistin, encoded by the plasmid-borne gene mcr-1, was first identified in animal and clinical samples from China in November 2015 and has subsequently been reported from numerous other countries. In April 2016, mcr-1 was identified in a carbapenem-susceptible Escherichia coli strain from a clinical sample in the United States, followed by a second report from a carbapenem-susceptible E. coli strain originally isolated in May 2015. We report the isolation and identification of an E. coli strain harboring both colistin (mcr-1) and carbapenem (blaNDM-5) resistance genes, originally isolated in August 2014 from urine of a patient with recurrent urinary tract infections. To our knowledge, this is the first report in the United States of a clinical bacterial isolate with both colistin and carbapenem resistance, highlighting the importance of active surveillance efforts for colistin- and carbapenem-resistant organisms.

Risk factors for nontuberculous mycobacterial infections in solid organ transplant recipients: a case–control study

The epidemiology of nontuberculous mycobacteria (NTM) disease in solid organ transplant recipients is poorly defined.

A report of human herpesvirus 6–associated encephalitis in a solid organ transplant recipient and a review of previously published cases

Human herpesvirus 6 (HHV‐6) is a common pathogen among children, classically presenting as fever and rash that resolve without specific therapy (exanthem subitum or roseola infantum). Also identified as a pathogen in hematopoietic cell transplant and solid organ transplant (SOT) recipients, it has been recognized as a cause of limbic encephalitis, characterized by confusion and amnesia, with magnetic resonance imaging findings of T2 hyperintensity of the amygdala and hippocampus. We report a case of limbic encephalitis associated with HHV‐6 infection in a liver transplant recipient, and we review previously reported cases of HHV‐6 encephalitis in SOT recipients. Liver Transpl 15:1242–1246, 2009.

Gender differences in the relationship between symptoms of depression and high-sensitivity CRP.

Background:Depression has been associated with increased risk of cardiovascular disease. The inflammatory marker C-reactive protein (CRP) has also been identified as an independent predictor of short- and long-term cardiovascular disease events. Inflammation may influence the relationship between depression and cardiovascular disease.Objective:The objective of this study was to investigate the association between symptoms of depression and high-sensitivity CRP (hs-CRP) in an obese clinical population. We also sought to determine whether this relationship was different in men and women, given prior reports of a gender effect.Methods:Symptoms of depression and hs-CRP were measured in 390 participants enrolled in a weight loss intervention trial that was delivered in a primary care setting. Symptoms of depression were evaluated with the Patient Health Questionnaire-8 (PHQ-8), in which a score ⩾10 is consistent with major depression.Results:A total of 58 (15.2%) participants reported a PHQ-8 score ⩾10. The median (interquartile range) hs-CRP concentration was significantly higher in participants with symptoms consistent with major depression (7.7 (4.2–13) mg l−1) compared with those without depression (5.1 (3–9.7) mg l−1; P<0.01). Symptoms consistent with major depression were significantly associated with log-transformed hs-CRP concentrations in an analysis adjusted for age, gender, obesity class and other metabolic variables (P=0.04). When interaction by gender was examined, this relationship remained significant in men (P<0.01) but not in women (P=0.32).Conclusions:Symptoms consistent with major depression were significantly associated with hs-CRP in men only, even after adjusting for age, obesity class, metabolic variables and medications known to affect inflammation. This finding suggests that there are biologic differences between men and women that may modify the relationship between hs-CRP and depression. Further studies are needed to elucidate the biologic basis for these findings.

Isoniazid-Resistant Tuberculous Meningitis, United States, 1993-2005

To determine patient characteristics associated with isoniazid resistance in cases of tuberculous meningitis, we conducted a cross-sectional study by using data from the US National Tuberculosis Surveillance System during 1993–2005. Foreign-born patients were more likely to be infected with an isoniazid-resistant strain.

Effectiveness of interventions in reducing antibiotic use for upper respiratory infections in ambulatory care practices.

The objective was to evaluate the effect of separate interventions on antimicrobial prescribing for uncomplicated upper respiratory tract infections. The authors conducted a quasi-experimental pre-post study with concurrent control groups for each intervention. Academic detailing led to a significant reduction in unnecessary antibiotic prescribing. However, there was no significant change in antibiotic prescribing in response to educational mailings to providers or to provider involvement in patient mailings. Organizations that seek to reduce inappropriate use of antibiotics should use proven approaches, even when they are more expensive.

Deaths from necrotizing fasciitis in the United States, 2003–2013

Necrotizing fasciitis (NF) is a life-threatening infection requiring urgent surgical and medical therapy. Our objective was to estimate the mortality burden of NF in the United States, and to identify time trends in the incidence rate of NF-related mortality. We obtained data from the National Center for Health Statistics, which receives information from death certificates from all states, including demographic information and cause of death. The U.S. Multiple Cause of Death Files were searched from 2003 to 2013 for a listing of NF (ICD-10 code M72.6) as either the underlying or contributing cause of death. We identified a total of 9871 NF-related deaths in the United States between 2003 and 2013, corresponding to a crude mortality rate of 4·8 deaths/1,000,000 person-years, without a significant time trend. Compared to white individuals, the incidence rate of NF-associated death was greater in black, Hispanic, and American Indian individuals, and lower in Asian individuals. Streptococcal infection was most commonly identified in cases where a pathogen was reported. Diabetes mellitus and obesity were more commonly observed in NF-related deaths compared to deaths due to other causes. Racial differences in the incidence of NF-related deaths merits further investigation.

Long-term virologic outcomes following bariatric surgery in patients with HIV

The management of morbid obesity and its metabolic complications among HIV-infected patients requires a multi-disciplinary approach, with surgical interventions as one option. We sought to assess the long-term durability of ART among HIV-infected patients undergoing bariatric procedures for the management of morbid obesity. During the study period, 7 patients underwent a bariatric surgery procedure for the management of morbid obesity: 3 patients underwent sleeve gastrectomy, 2 patients underwent laparoscopic banding, and 2 patients underwent Roux-en-Y gastric bypass surgery. Overall, the proportion of undetectable HIV viral load levels did not change after the bariatric procedures, although 2 patients did require temporary cessation of medications due to procedure-related complications. Sleeve gastrectomy and Roux-en-Y gastric bypass were safe and effective among morbidly obese HIV-infected patients in our clinic population.

Factors Associated with a Willingness to Accept Rapid HIV Testing in an Urban Emergency Department

Emergency Departments (EDs) provide primary healthcare to many underserved persons without access to preventive healthcare elsewhere. We conducted a cross-sectional study to test the hypothesis that patients are more likely to express a willingness to accept rapid HIV testing in the ED if they lack access to preventive healthcare elsewhere. Medicaid insurance, younger age, lack of a usual place of healthcare, high perceived HIV risk, and actual HIV risk were associated with increased HIV test acceptance. These results support the need for and acceptability of rapid HIV testing in the ED particularly for individuals who may lack access to this preventive healthcare screening elsewhere.

Isoniazid clearance is impaired among human immunodeficiency virus/tuberculosis patients with high levels of immune activation

AIMS Immune activation, which is characteristic of both tuberculosis (TB) and human immunodeficiency virus (HIV) infection, is associated with impaired drug metabolism. We tested the hypothesis that elevated levels of systemic immune activation among adults with HIV/TB initiating antiretroviral therapy (ART) would be associated with impaired clearance of isoniazid. METHODS We conducted a prospective observational study of isoniazid pharmacokinetics (PK) and systemic immune activation prior to and 1 month after ART initiation. Nonlinear mixed effects analysis was performed to measure the covariate effect of immune activation on isoniazid clearance in a model that also included N‐acetyltransferase‐2 (NAT‐2) genotype and interoccasional variability on clearance (thereby analyzing the PK data before and after ART initiation in a single model). RESULTS We enrolled 40 patients in the PK visit prior to ART, and 24 patients returned for the second visit a median of 33 days after initiating antiretroviral therapy. The isoniazid concentration data were best described by a two‐compartment model with first‐order elimination. After accounting for NAT‐2 genotype, increasing levels of CD38 and HLA‐DR expression on CD8+ T cells (CD38+DR+CD8+) were associated with decreasing isoniazid clearance. CONCLUSION HIV/TB patients with high levels of immune activation demonstrated impaired isoniazid clearance. Future efforts should determine the role of this relationship in clinical hepatotoxicity events.